PMID- 26665541 TI - Using business analytics to improve outcomes. AB - Orlando Health has brought its hospital and physician practice revenue cycle systems into better balance using four sets of customized analytics: Physician performance analytics gauge the total net revenue for every employed physician. Patient-pay analytics provide financial risk scores for all patients on both the hospital and physician practice sides. Revenue management analytics bridge the gap between the back-end central business office and front-end physician practice managers and administrators. Enterprise management analytics allow the hospitals and physician practices to share important information about common patients. PMID- 26665542 TI - Specificity is key to successful application of analytics. AB - More data do not necessarily equate to better analytics. Choosing the right analytics tools and applying them to specific areas leads to better results. A Midwest hospital used single-point metrics to identify underperforming facilities and drive improvements. PMID- 26665543 TI - Reducing lost revenue from inpatient medical-necessity denials. AB - Payment denials based on questions of medical necessity have increased significantly for many hospitals, while the odds of mounting a successful appeal have diminished. Instead of focusing primarily on making appeals more effective, hospitals should construct a strategy for reducing the incidence of medical necessity denials through the collection and analysis of denials data. Hospitals can break down the data to produce optimal approaches at both the case management and service levels to minimizing lost revenue from medical-necessity denials. PMID- 26665544 TI - Curing an ill healthcare system: transparent multilateral benefits, cost, and quality. AB - A transparent, smart, multilateral benefits system can lead the way to healthcare reform with health and economic benefits for all based on: Provider competition guided by quality measurements, clinical nuance, and price competition. Shared risk among consumers, employers, and plans. Economic incentives for all parties. PMID- 26665545 TI - maximizing patient care revenue throughout a major HIS conversion. AB - Appointing a revenue point person during a health information system (HIS) conversion ensures revenue remains a priority. Part of the preparation for an HIS conversion should be to clean up the accounts receivable backlog, which provides a revenue boost. Flexible staffing approaches to augment staff, as necessary, should be adopted to address areas that will require heightened attention during the conversion. The postconversion strategy, including audits and staff education, should aim to derive maximum value from the new system. PMID- 26665546 TI - Expanding actionable BI and BA to create a health maintenance continuum. PMID- 26665547 TI - Accounting for the value of physician practices. PMID- 26665549 TI - Salient trends in capital investment and revenue cycle. PMID- 26665548 TI - A midcourse correction for Medicare ACOs. PMID- 26665550 TI - Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene. AB - BACKGROUND/AIM: Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha motor neurons in the spinal cord and the medulla oblongata, causing progressive muscle weakness and atrophy. The aim of this study was to determine association between the SMN2 gene copy number and disease phenotype in Serbian patients with SMA with homozygous deletion of exon 7 of the SMN1 gene. METHODS: The patients were identified using regional Serbian hospital databases. Investigated clinical characteristics of the disease were: patients' gender, age at disease onset, achieved and current developmental milestones, disease duration, current age, and the presence of the spinal deformities and joint contractures. The number of SMN1 and SMN2 gene copies was determined using real-time polymerase chain reaction (PCR). RESULTS. Among 43 identified patients, 37 (86.0%) showed homozygous deletion of SMN1 exon 7. One (2.7%) of 37 patients had SMA type I with 3 SMN2 'copies, 11 (29.7%) patients had SMA type II with 3.1 +/- 0.7 copies, 17 (45.9%) patients had SMA type III with 3.7 +/- 0.9 copies, while 8 (21.6%) patients had SMA type IV with 4.2 +/- 0.9 copies. There was a progressive increase in the SMN2 gene copy number from type II towards type IV (p < 0.05). A higher SMN2 gene copy number was associated with better current motor performance (p < 0.05). CONCLUSION: In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected. PMID- 26665551 TI - Analysis of the mineral composition of hypomineralized first permanent molars. AB - BACKGROUND/AIM: Hypomineralization of molars and incisors (molarincisor hypomineralization--MIH) is defined as enamel hypomineralization of systemic origin of one or more of the four first permanent molars, which may be associated with changes in the maxillary, and less frequently in the permanent mandibular in cisors. The aim of this study was to investigate the mineral content in hypomineralized teeth as a contribution to understanding the origin of these changes, which will be important for effective restorative approach. METHODS: A total of 10 extracted first permanent molars diagnosed with MIH were used in the study as the experimental group, and intact first premolars extracted for orthodontic reasons were used as the control group. A certain surface of hypomineralized and healthy enamel and dentin was analyzed using a scanning electron microscope equipped with an energy-dispersive spectrometer (SEM/EDS). RESULTS: By conducting quantitative chemical analysis of the distribution of the basic chemical elements, it was found that the concentration of calcium (Ca) and phosphorus (P) was significantly higher in healthy enamel (Ca = 28.80 w%, and P = 15.05 wt%) compared to hypomineralized enamel (Ca = 27.60 wt% and P = 14.32 wt/o). Carbon (C) concentration was statistically significantly higher in hypomineralized enamel (C = 11.70 wt%) compared to healthy enamel (C = 10.94 wt%). Hypomineralized and healthy enamel did not differ significantly regarding the ratio of calcium and phosphorus concentrations whereas the ratio of calcium and carbon concentrations was statistically significantly higher in healthy enamel compared to hypomineralized enamel. CONCLUSION: Concentration of the main chemical elements, primarily calcium and phosphorus, is significantly reduced in hypomineralized enamel whereas carbon concentration is increased compared to healthy enamel. PMID- 26665552 TI - Apparent diffusion coefficient in the evaluation of cerebral gliomas malignancy. AB - BACKGROUND/AIM: Magnetic resonance imaging (MRI) is a key modality not only for lesion diagnosis, but also to evaluate the extension, type and grade of the tumor. Advanced MRI techniques provide physiologic information that complements the anatomic information available from conventional MRI. The aim of this study was to determine whether there is a correlation between apparent diffusion coefficient (ADC) maps of intracranial glial tumors and histopathologic findings and whether ADCs can reliably distinguish low-grade from high-grade gliomas. METHODS: This retrospective study included 25 patients with MRI examination up to seven days before surgery, according to the standard protocol with the following sequences: T1WI, T2WI, FLAIR, DWI and post contrast T1WI. Data obtained from DW MRI were presented by measuring the value of ADC. The ADC map was determined by utilizing Diffusion-Perfusion (DP) Tools software. All the patients underwent surgical resection of the tumor. Histological diagnosis of tumors was determined according to the World Health Organization (WHO) classification. The ADC values were compared with the histopathologic findings according to the WHO criteria. RESULTS: The ADC values of astrocytomas grades I (0.000614 +/- 0.000032 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm2/s) and the ADC values of glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values of astrocytomas grades II (0.000530 +/- 0.000114 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm2/s) and glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values of anaplastic astrocy omas (0.000436 +/- 0.000016 mm2/s) were significantly higher (< 0.001) than the ADC values of glioblastomas multiforme (0.000070 +/- 0.000008 mm2/s). The ADC values in the cystic part of the tumor for astrocytomas grades I (0.000775 +/- 0.000023 mm2/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000119 +/- 0.000246 mm2/s) and glioblastomas multiforme (0.000076 +/- 0.000004 mm2/s). The ADC values astrocytomas grades II (0.000511 +/- 0.000421 mm2/s) were significantly higher (< 0.001) than the ADC values of glioblastomas multiforme (0.000076 +/- 0.000004 mm2/s). CONCLUSION: DWI with calculation of ADC maps can be regarded as a reliable useful diagnostic tool, which indirectly reflects the proliferation and malignancy of gliomas. The ADCs maps can both predict the results of histopathological tumor and distinguish between low- and high-grade gliomas, and provide significant information for presurgical planning, treatment and prognosis for patients with high-grade astrocytomas. PMID- 26665553 TI - Intravitreal bevacizumab injection alone or combined with macular photocoagulation compared to macular photocoagulation as primary treatment of diabetic macular edema. AB - BACKGROUND/AIM: Within diabetic retinopathy (DR), diabetic macular edema DIE) is one of the leading causes of the loss of visual acuity. The aim of this study was to determine the efficacy of the intravitreal vascular endothelial growth factor (VEGF) inhibitor application alone or combined with macular focal/grid lasephotocoagulation compared with laser treatment alone. METHODS: This prospective randomized clinical trial included 72 patients (120 treated eyes) with varying degrees of DR and DME. The DME treatment included intravitreal VEGF inhibitor bevacizumab (Avasting) application, with and without laser treatment. Bevacizumab (1.25 mg/0.05 mL) was administered intravitreally in 4-6-week intervals. Laser is applied 4-6 weeks after last dose of the drug as a part of combined treatment, or as the primary treatment. RESULTS: The mean reduction in central macular thickness (CMT) for the eyes (n = 31) treated with bevacizumab alone was 162.23 .rm, for the eyes (n = 53) treated with combined treatment the mean reduction in CMT was 124.24 pm, both statistically significant at p < 0.001. Laser macular photocolagulation as a part of combined treatment (in 53 eyes) significantly contributed to the CMT reduction, based on the paired t-test results (366.28 vs. 323.0 pLm at p < 0.05). In our study, the mean visual acuity improvement of 0.161 logMAR was achieved in the group of eyes treated with bevacizumab alone, and 0.093 logMAR in the group with combined treatment, both statistically significant atp < 0.05. The effect of laser photocolagulation alone on visual acuity and'CMT was not statistically significant. CONCLUSION: Treatment with bevacizumab alone or within combined treatment is more effective in treating DME than conventional macular laser treatment alone, both anatomically and functionally. PMID- 26665554 TI - Catheter-associated urinary tract infection in a surgical intensive care unit. AB - BACKGROUND/AIM: Because patients in intensive care units usully have an urinary catheter, the risk of urinary tract infection for these patients is higher than in other patients. The aim of this study was to identify risk factors and causative microrganisms in patients with catheter-associated urinary tract infection (CAUTI) in the Surgical Intensive Care Unit (SICU) during a 6-year period. METHODS: All data were collected during prospective surveillance conducted from 2006 to 2011 in the SICU, Military Medical Academy, Belgrade, Serbia. This case control study was performed in patients with nosocomial infections recorded during surveillance. The cases with CAUTIs were identified using the definition of the Center for Disease Control and Prevention. The control group consisted of patients with other nosocomial infections who did not fulfill criteria for CAUTIs according to case definition. Results. We surveyed 1,369 patients representing 13,761 patient days. There were a total of 226 patients with nosocomial infections in the SICU. Of these patients, 64 had CAUTIs as defined in this study, and 162 met the criteria for the control group. Multivariate logistic regression analysis identified two risk factors independently associated to CAUTIs: the duration of having an indwelling catheter (OR = 1.014; 95% CI 1.005-1.024; p = 0.003) and female gender (OR = 2.377; 95% CI 1.278-4.421; p = 0.006). Overall 71 pathogens were isolated from the urine culture of 64 patients with CAUTIs. Candida spp. (28.2%), Pseudomonas aeruginosa (18.3%) and Klebsiella spp. (15.5%) were the most frequently isolated microorganisms. CONCLUSIONS: The risk factors and causative microrganisms considering CAUTIs in the SICU must be considered in of planning CAUTIs prevention in this setting. PMID- 26665555 TI - Diagnostic value of serial measurement of C-reactive protein in serum and matrix metalloproteinase-9 in drainage fluid in the detection of infectious complications and anastomotic leakage in patients with colorectal resection. AB - BACKGROUND/AIM: Postoperative infectious complications are one of the most important problems in surgical treatment of colorectal cancer (CRC), being present in up to 40% of patients. The aim of this paper was to establish the significance of serial measurement of C-reactive protein (CRP) in serum and matrix metalloproteinase-9 (MMP-9) in drainage fluid for the detection of infectious complications and anastomotic leakage (AL) in patients with colorectal resection. METHODS: CRP and MMP-9 values in serum and drainage fluid, respectively, were measured on the first, third, fifth, and seventh postoperative day (POD) in 150 patients with colorectal resection and primary anastomosis. The values obtained were compared between the patients without complicatons and those with surgical site and remote infections and AL. RESULTS: Surgical site infections (SSIs) were observed in 41 (27.3%), and remote infections in 10 (6.7%) patients. Clinically evident AL was observed in 15 (10/6) patients. In 82% of the patients with SSIs, serum CRP value on POD 5 exceeded 82 mg/L, with 81% specificity. AL was reported in 85% and 92% of the patients on PODs 5 and 7, respectively, with CRP values of 77 mg/L and 90 mg/L, respectively. The specificity was 77% for POD 5 and 88% for POD 7. All the patients with CRP values exceeding 139 mg/L on POD 5 had some of SSIs and/or AL. The mean values of MMP-9 were not statistically different between the group without complications (n = 99) and the group with AL (n = 15). CONCLUSION: Serial measurement of CRP is recommended for screening of infectious complications of colorectal resection. Patients with CRP values above 139 mg/L on POD 5 cannot be discharged from hospital, and require an intensive search for infectious complications, particularly AL. MMP-9 measurement in drainage fluid is not relevant in the detection of AL in patients with colorectal resection. PMID- 26665556 TI - Artificial saliva effect on toxic substances release from acrylic resins. AB - BACKGROUND/AIM: Acrylic-based resins are intensively used in dentistry practice as restorative or denture-base materials. The purpose of this study was to analyze the surface structure of denture base resins and the amount of released potentially toxic substances (PTS) immediately upon polymerization and incubation in different types of artificial saliva. METHODS: Storage of acrylic samples in two models of artificial saliva were performed in a water bath at the temperature of 37 +/- 1 degrees C. Analysis of the surface structure of samples was carned out using scanning electronic microscopy analysis immedidtely after polymerization and after the 30-day incubation. The amounts of PTS per day, week and month extracts were measured using high-pressure liquid chromatography. RESULTS: Surface design and amount of PTS in acrylic materials were different and depended on the types and duration of polymerization. The surfaces of tested acrylates became flatter after immersing in solutions of artificial saliva. The degree of acrylic materials release was not dependent on the applied model of artificial saliva. CONCLUSION: In order to improve biological features of acrylic resin materials, it was recommended that dentures lined with soft or hard cold polymerized acrylates should be kept at least 1 to 7 days in water before being given to a patient. So, as to reach high degree of biocompatibility preparation of prosthetic restorations from heat-polymerized acrylate was unnecessary. PMID- 26665557 TI - The expression and localization of estrogen receptor beta in hyperplastic and neoplastic prostate lesions. AB - BACKGROUND/AIM: Benign acini in benign prostatic hyperplasia (BPH) are lined with pseudostratified cylindrical epithelium with a continuous basal cell layer. Adenocarcinoma of the prostate is the most common cancer in men. High gradus prostatic intraepithelial neoplasia (HGPIN) lesions precede invasive cancer. Prostate adenocarcinoma (PCa) implies a complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor (ER) is located in nuclei of acinar basal and secretory cells and partially in stromal cells. The aim of this research was to demonstrate and localize ER in BPH and in PCa of different Gleason scores. Considering literature data for ER-beta. expression in different morphologic prostate lesions, it is assumed that there is expression of ER-beta in most moderately differentiated PCa, and that the observed receptor expression is lost with increasing of the Gleason score. METHODS: Four groups of patients were formed: the control with BPH and three experimental groups with PCa of different grades and scores, according to the Gleason grading system. The patients were male of various ages suspected of PCa, based on clinical and laboratory parameters. The study was conducted in a period 2010-2012. None of the patients received prior hormonal therapy. Sextant byopsies with BPH and PCa were treated for ER-beta (Novacastra). Localization and intensity of ER-beta expression is reported through the score: 0 = zero; 1 = < 1%; 2 = 1-10%; 3=11 33%; 4= 34-66%; 5- > 66%. Positive fibroblasts and endothelial cells are used for comparison. RESULTS: ER-beta expression in acinar epithelial cells was the weakest in well-differentiated adenocarcinoma. A decline of ER-beta expression was noticed in malignant lesions of the prostate vs. benign ones. Less differentiated adenocarcinomas showed a decrease of ER-beta expression in basal and in the secretory cells. ER-beta expression in basal cells was stronger than in secretory ones in BPH and well-differentiated adenocarcinoma. CONCLUSION: ER beta expression was most pronounced in BHP samples and declined in malignant prostate lesions. This finding supports statement on anticiproliferative role of ER-beta in prostatic tissue. PMID- 26665558 TI - Structural features of arterial grafts important for surgical myocardial revascularization: Part I--Histology of the internal thoracic artery. PMID- 26665559 TI - Opto-magnetic imaging spectroscopy in characterization of the tissues during hyperbaric oxygen therapy. AB - BACKGROUND/AIM: Opto-magnetic imaging spectroscopy (OMIS) was used as a novel method to detemine tissue molecular conformation changes during hyperbaric oxygen (HBO) therapy. The aim of this study was to examine the usefulness of OMIS for the assessment of HBO therapy effectiveness on the diseased tissue. METHODS: OMIS is concerned with obtaining paramagnetic/diamagnetic properties of materials, related to the presence of unpaired/paired electrons based on their interaction with visible light. The basic tool is light of wavelength in the range between 400 nm and 700 nm and its interaction with tissue. The study included 22 subjects: 16 angiopathy patients and 6 healthy subjects as the control group. OMIS was used with patients on the 1st, 10th and 20th session and with the control group on the 1st, 10th and 20th day without HBO therapy in between. RESULTS: The obtained results showed that healthy skin of all the control group subjects had the same shape curve. In the angiopathy patient group, before the first session OMIS showed tissue disorder and after the last session results resembled more closely the results in healthy tissue. The differences in the tissue state in the angiopathy group before each session were noticeable, showing normalized tissue under the influence of HBO. CONCLUSION: The results show that OMIS could be used as a diagnostic tool for detection of the tissue state before and after the HBO therapy. PMID- 26665560 TI - Idionathic retroneritoneal fibrosis: A Report on 15 Patients. AB - BACKGROUND/AIM: Retroperitoneal fibrosis (RPF) repre sents a chronic pathological process characterized by fibro sis which entraps and compresses the ureters and the grea blood vessels in the retroperitoneal space. A specific form of RPF is idiopathic RPF, an uncommon collagen vasculaj disease of unclear etiology. The series of 15 patients whicl underwent open surgical repair due to idiopathic RPF is presented herein. METHODS: From 1989 to 2012, 11 male and 4 female patients underwent surgery due to primar RPF. The ureters were entrapped unilaterally (7 patients), or bilaterally (8 patients). Major symptoms included low bacl pain due to hydronephrosis (9 patients), uremia (4 patients) and urinary tract infection (2 patients). The diagnosis was based on intravenous urography (IVU), retrograde uretero pyelography and computed tomography (CT). RESULTS: Surgical procedures included intraperitoneal ureteral dis placement (8 patients) and ureteral wrapping with omental flap (6 patients). One patient underwent bilateral uretera stenotic segments resection and oblique ureterography, followed by wrapping with omental flap. Pathological examination confirmed primary RPF in all patients. The meat operative time was 3.5 h (range 2.5-4.5 h). The average in trahospital stay was 21 days (range 16-26 days). The meat follow up was 32 months (6-46 months). During the follow up, 12 patients had improvement on IVU. CONCLUSION: Early recognition of signs and symptoms of RPF is of the utmost importance for the outcome. Surgical procedures including ureteral wrapping with omental flap, or intraperi toneal ureteral displacement, usually represent definitive treatment. PMID- 26665561 TI - Acquired cystic disease and renal cell carcinoma in hemodialysis patients--A case report on three patients. AB - INTRODUCTION: Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. CASE REPORT: We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow-up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. CONCLUSION: Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with end-stage renal disease and RCC is mostly good because these tumors are usually of indolent course. PMID- 26665562 TI - Melanoma of the sinonasal mucosa: A report on the two cases and a review of the literature. AB - INTRODUCTION: Primary mucosal melanoma of the sinonasal tract is a rare neoplasm, accounting for less than 1% of all melanomas. It has an aggressive and unpredictable biologic behavior characterized by frequent incidence of local recurrence, local and distant metastasis of the disease. CASE REPORT: This report summarizes the results of the previous research concerning sinonasal mucosal melanoma, and by the example of the two patients suffering from mucosal melanoma, we described clinical and histopathological features of this rare neoplasm and our experience in its diagnosis and treatment. CONCLUSION: Only histopathological analysis complemented by immunobistochemical analysis contributes to early and accurate diagnosis of the disease. PMID- 26665563 TI - Conservative treatment of bronchobiliary fistula evaluated with magnetic resonance imaging. AB - INTRODUCTION: Bronchobiliary fistula (BBF) is a pathological communication between the bronchial system and the biliary tree that presents with bilioptysis. Many conditions can cause its development. There is still no optimal therapy for BBF. Conservative treatment is rarely indicated, as was published before in a few cases. CASE REPORT: We presented a 71-year-old Caucasian Serbin woman with BBF secondary to previous laparotomy due to multiple echinococcus liver cysts. The diagnosis was established by the presence of bilirubin and bile acids in sputum and magnetic resonance cholangiopancreatography (MRCP). A repeat MRCP performed after conservative procedure, did not reveal fistulous communication. CONCLUSION: We suggest that in small and less severe fistulas between the biliary and the bronchial tract, conservative treatment may be used successfully, and invasive treatment methods are not needed in all patients. PMID- 26665564 TI - Sexual activity of women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS)- preliminary study. AB - OBJECTIVES: The aim of the study was to assess sexual activity of women with Mayer-Pokitansky-K0ster-Hauser syndrome (MRKHS) in relation to age-matched con trots. The hypotheses on differences betwedn them in regard to various types of sexual activity and its characteristics were verified. MATERIAL AND METHODS: 31 patients with MRKHS and 31 healthy women were examined. Psychosexual biography by M. Beisert was used to gain information on autoerotic and dyadic behavior: Phi coefficient and U Mann-Whitney test were performed. RESULTS: Women with the MRKHS started autoerotic be ha vior at a similar age (U=58, 00; ns), practiced masturbation with the same frequency (in adolescence--U=350,00; ns and adulthood- U=137.50; ns) and manifested a similar level of sexual arousal (U=326,50; ns) as the age-matched controls. They declared experiencing vaginal (Phi=0.507; p<0.001) and oral (Phi=0.318; p<0.05) intercourse less frequently than healthy women. They also initiated dyadic sexual activity at a higher age than the controls (petting U=182,00; p<0.01; req=0.41; vaginal intercourse (U=64.00; 0<0.001; req = 0.59; oral contact (U=91.50; p<0.05; req=0.56) with exception of anal intercourse, where the age of initiation was the same in both groups (U=30,50; ns). Women in both groups experienced similar orgasm frequency during petting (U=108.50; ns), oral intercourse (U=97.50; ns), anal Tntercourse (U=25.50; ns). However, patients with the MPKHS reported significantly lower frequency of orgasm during vaginal intercourse (U=60.50; p<0.05; req=0.36). CONCLUSIONS: Sexual development of patients with the MRKHS and healthy women is partly similar Differences in dyadic sexual activity are not limited to vaginal intercourse thus are probably determined by biological conditions and their psychological implications. PMID- 26665565 TI - Conservative treatment of borderline ovarian tumors: the experience of one clinical center. AB - OBJECTIVES: Borderline ovarian tumors have favorable survival rates, however, prognostic factors are still discussed. The aim was to investigate the outcome for women treated conservatively with respect to different tumor-dependent and tumor-independent prognostic factors. MATERIAL AND METHODS: 194 women treated surgically between years 1978 and 2007. Influence of conservative or radical surgical treatment on survival was evaluated. RESULTS: The overall 5-year survival rate was 93.1% and 96.8% respectively for radical and conservative treatment. The mean time of survival was longer in women treated conservatively (p = 0.03), but this was an outcome of their younger age; when age was eliminated as a determining factor; the type of treatment had not influenced the length of postoperative survival (p=0.57). Conservative treatment was chosen more frequently for younger women. Factors that are detrimental to survival are age, postmenopausal detection of borderline ovarian tumors, an advanced stage of progression, a bilateral localization of tumors, the occurrence of invasive peritoneal implants and a serous rather than a mucinous histological type of borderline ovarian tumor more frequently occurred in women treated radically Borderline ovarian tumors recurred in 16.7% of women after conservative treatment and in 3.5% of women after radical treatment. Of women with preserved fertility 25.7% became pregnant at least once and 21.2% of the group as a whole delivered children at term; none of the pregnancies were fertility-assisted. CONCLUSIONS: Conservative treatment does not have a deleterious effect on the prognosis of women provided that unfavorable prognostic factors are identified. PMID- 26665566 TI - Pregnancy-dependent blood flow velocity changes in lower extremities veins in venous insufficiency. AB - INTRODUCTION: Venous insufficiency in pregnancy is associated witch an increased risk of complications. OBJECTIVES: The aim of the study was to analyse the venous system changes of the lower limbs during pregnancy and puerperium with or without venous insufficiency MATERIAL AND METHODS: The research was carried out on pregnant women divided into two groups according to the presence or lack of venous insufficiency The venous system was examined four times: between 11-14th, 18-22nd, 28-32nd gestational week and at the 6th week of puerperium. The doppler examination included the measurement of the blood flow velocity in selected deep veins of the lower limbs: common femoral vein, the superficial femoral vein and the popliteal vein. Consecutively the changes in the blood flow velocity during pregnancy and puerperium were compared between groups and finally to the results obtained in the 1st trimester RESULTS: The analysis of the blood flow showed that the blood flow velocity was statistically lower in the group with venous insufficiency Velocity changes in time showed, in majority of cases, a substantial reduction in the blood flow velocity in the third trimester in both groups. This blood flow velocity increases during the puerperium and does not differ from those observed in the first trimester Thus, the tendency of changes in the blood flow velocity were similar in character in both groups. CONCLUSIONS: The pregnancy related changes in venous system of lower extremities showed the reduction of blood flow velocity with advancing gestational age and were more evident in pregnancy complicated by venous insufficiency PMID- 26665567 TI - Thyroid antibodies in euthyroid and subclinical hypothyroidic pregnant women with autoimmune hypothyroidism: effects on hematological parameters and postpartum hemorrhage. AB - OBJECTIVES: The aim of the study was to investigate the relationship between thyroid antibodies and hematological parameters in euthyroid or subclinical hypothyroidic (S H) pregnant women with autoimmune hypothyroidism and to verity whether these pregnant women are affected by a higher rate of postpartum hemorrhage. MATERIAL AND METHODS: Thirty-six out hyroid and 21 S H pregnant women with autoimmune thyroid disease and 52 healthy pregnant women were evaluated. The relationship between thyroid hormones, thyroid antibodies level, the dosage of Levotroxin (LT4) and hematological parameters and the amount of postpartum bleeding was investigated. RESULTS: The mean platelet volume (MPV), was significantly higher in the SH group than in the euthyroid group and in the euthyroid group than healthy group (p<0.001). Hemoglobin (Hb) was significantly lower in both the SH group and the euthyroid group than control group (p<0.001). Other hematological parameters and the amount of postpartum bleeding did not differ between the groups. The correlation between Hb and fT3, FT4 was significant and positive, whereas between Hb and T SH was significant and negative (r=0.3 p<0.01, r=0.2 p=0.01, and r = -0.18 p=0.04, respectively). There was a significant and negative correlation between the PLT count and FT4, PT and FT3 (r = -0.2 p=0.01, r = -0.3 p<0.01, and r = -0.3 p<0.01, respectively). CONCLUSION: It has been described that being thyroid antibody-positive (TAb+) may be a risk factor for anemia and high MPV. However euthyroid and SH pregnant women with thyroid antibodies do not differ in terms of other coagulation parameters and postpartum hemorrhage from healthy controls. PMID- 26665568 TI - DRD1 and DRD4 dopamine receptors in the etiology of preeclampsia. AB - INTRODUCTION: Recent reports have suggested an association between genetic polymorphisms of dopamine receptors and the development of an increased risk of chronic hypertension, as well as preeclampsia (PE). OBJECTIVES: The aim of the study was to evaluate the impact of the -48A>G DRD1 and -521C>T DRD4 polymorphisms in the etiology of PE among Polish women. MATERIAL AND METHODS: Ninety-eight preeclamptic women and 120 healthy pregnant controls were enrolled in the study The investigated polymorphisms of the DRD 1 and DRD4 genes were identified using PCR/RFLP methods. RESULTS: As far as the -48A>G DRD 1 polymorphism is concerned, the mutated -48GG genotype was more often found in controls (14.2%) than in the PE group (10.2%, ns), and the subgroup with severe PE (8.2%). Also, the frequency of the mutated -48G allele was higher in controls (39.6%) than in the PE group (33.2%, ns), and in the subgroup with severe PE (31.6%, ns). As for the -521C>TDRD4 polymorphism, a similar occurrence of the mutated -521 TTgenotype and the -521T allele in all of the investigate groups was observed. Lower serum concentrations of total protein (5.59 g/L and 5.57 g/L vs. 6.17 g/L in carriers of the -52100 genotype, p=0.02) were noted in patients with the mutated homozygous -521 TT genotype and heterozygous -521CT genotype of DRD4. CONCLUSIONS: The obtained results suggest a possible protective role of the mutated -48G DRD1 allele in the etiology of preeclampsia, especially its severe form. The presence of the mutated -521 T DRD4 allele could influence the decrease of total blood protein in preeclamptic patients. The observed frequency of dopamine DRD1 and DRD4 polymorphisms is similar to the distribution of these variants in other Caucasian populations. PMID- 26665569 TI - Expression of collagen in ovular membranes of pregnant smokers and non-smokers: a pilot study. AB - OBJECTIVE: Our study compared the amount of total collagen and type I collagen in ovular membranes of pregnant smokers and non-smokers. MATERIAL AND METHODS: The study group consisted of 14 pregnant smokers at 24-36 weeks of gestation; 39 pregnant non-smokers between 24-36 weeks of gestation comprised the control group. The expressions of total collagen and type I collagen were analyzed using two histological sections of the fetal membranes. The assessment of total collagen was performed using the Picro-Cirius red stain, and type I collagen expression was determined by means of immunohistochemistry The Mann-Whitney test was applied to verify possible differences between the groups. RESULT: The average area covered by total collagen was lower in smokers (20630.45 microm2) as compared to non-smokers (24058.61 microm2), although the difference was not statistically significant (p = 0.454). Comparison involving collagen type I deemed similar results (20001.33 microm2 vs. 25328.29 microm2, p = 0.158). CONCLUSION: The amount of total collagen and type I collagen was lower in ovular membranes of pregnant smokers as compared to non-smokers, although the difference was not statistically significant. PMID- 26665570 TI - Prediction of short-term newborn infectious morbidity based on maternal characteristics in patients with PPROM and Ureaplasma species infection. AB - OBJECTIVES: Preterm premature rupture of membranes (PPROM) complicates about 5% of pregnancies. Ureaplasma species is the most common pathogen found in the amniotic fluid in pregnancieneonatal outcome. The aim of the following study was to evaluate the impact of colonization with the Ureaplasma spp. on pregnant women with PPROM, coin fection with different microorganisms, and antimicrobial treatment on neonatal outcome. MATERIAL AND METHODS: The study included 30 women with PPROM hospitalized in Division of Reproduction in s complicated by PPROM. It is speculated that it requires a coin fection to produce unfavorable Poznan's K. Marcinkowski University of Medical Sciences. Swabs from cenvical canal were obtained for the identifidation of bacterial and ureaplasma tic infections by culture and POR. RESULTS: The presence of any infection during the pregnancy a fter PP ROM was con firmed in 22 patients (Ureaplasma spp. in 12 patients, coin fection in 10 women). The cure rate for Ureaplasma species and other infections was 17% (2/12 patients) and 23% (5/22 patients), respectively There was no correlation between Ureaplasma species infection, coin fection, and cure status with the infection in the newborn. The PPROM to delivery duration also did not affect the newborn infection status. A negative relationship with leukocyte level was detected in patient with newborn infection. CONCLUSIONS: The presence of colonization with Ureaplasma species is not attributable to neonatal short-term morbidity The evaluation of maternal biochemical and microbiological data, regardless of the duration of the pregnancy after PPROM or the cure status, does not add any insight into the newborn infection status. PMID- 26665571 TI - [Evaluation of carbetocin and oxytocin efficacy in prevention of postpartum hemorrhage in women after cesarean section]. AB - INTRODUCTION: Postpartum hemorrhage (PPH) constitutes the main cause of delivery related maternal mortality worldwide. Identification of the risk factors, as well as knowledge about preventive measures and adequate management, allow to limit blood loss. Oxytocin, carbetocin, methylergometrine, dinoprostone, suiprostone, and misoprostol are commonly used drugs in prevention of PPH. OBJECTIVES: The aim of the study was to evaluate the efficacy of carbetocin and oxytocin in prevention of PPH after cesarean section. MATERIAL AND METHODS: The study included 130 female patients after C-section who received 1 00 pg of carbetocin i.v. as a preventive agent after the surgery The control group consisted of 60 women who received 10 units of oxytocin i.v. In the study the risk factors for PPH were determined, and hemoglobin and hematocrit values before and 12 hours after birth, as well as blood loss and the need to use other prevyentfive and operational methods were evaluated. Results were compared between the groups. Statistical analysis was performed with the use of Statistica for hemoglobin and hematocrit values. The p-value of < or = 0.05 was considered as statistically significant. RESULTS: Risk factors for PPH occurred in almost 100% of the women with carbetocin and in 90% of the women with oxytocin. The decrease in hemoglobin and hematocrit levels was not statistically significant, although a greater drop was detected in the group with oxytocin (hemoglobin - 1.24 vs. 1.17 g%, hematocrit - 3.26 vs. 2.93%). The decrease in hematological values was not statistically significant between both groups. In the group with'carbetocin, there was no need for additional pharmacological therapy or operative procedures. No adverse events in either of the groups were observed. CONCLUSIONS: (1.) Carbetocin effectively prevents PPH after C-section. (2.) Carbetocin seems to have high efficiency in PPH prevention in pregnant women classified to the PPH risk group. (3.) Efficacy of Carbetocin in PPH prevention is higher than oxytocin. PMID- 26665572 TI - [Rapid diagnosis of the most common fetal aneuploidies with the QF-PCR method--a study of 100 cases]. AB - The aim of the study was to assess whether commercial kit QF-PCR can be used as the only method for rapic prenatal dia gnosis of chromosomes 13, 18, 21, X and Y aneuploidies, omitting cell culture and complete cyt6genetik analysis of fetal chromosomes. MATERIAL AND METHODS: DNA from amniocytes (94 cases) and trophoblast cells (6 cases) was analyzed witt QF-PCR according to the manufacturer's protocol. The obtained products were separated using ABI 310 Genetic Analyzer and the resulting data were analyzed using GeneMarker software. RESULTS: The results of QF-PCR were obtained in 95 out of 100 cases (95%). Abnormalities were found in 28 casea (29.5%). All these results were confirmed in subsequent cytogenetic analysis. Normal results were obtained in 62 patients (70.5%). However in that group, we found three chromosomal aberrations other than those analyzed b3 QF PCR. Additionally two abnormal and three normal karyotypes were found in patients with inconclusive QF-POF results. CONCLUSIONS: QF-PCR is a fast and reliable tool for chromosomal aneuploidy analysis and can be used as the only method without a full analysis of the karyotype, but only in cases of suspected fetal 13, 18, 21 trisomy or numerica aberrations of X chromosome. In other cases, fetal karyotype analysis from cells obtained after cell culture should be offered to the patient. PMID- 26665573 TI - [Pregnancy and labor after fertility-sparing surgical management of cervical cancer]. AB - OBJECTIVE: The aim of the study was to evaluate the possibility of conception and the course of pregnancy in women with cervical cancer (FIGO IA and IB1), who underwent fertility-sparing surgical management, i.e. surgical conization or radical vaginal trachelectomy with laparoscopic lymphadenectomy. MATERIAL AND METHODS: A total of 80 patients treated surgically due to cervical cancer constituted the study group. Out of them, 65 (85%) women underwent surgical conization (43--FIGO IA1 and 25--FIGO IA2), and 12 (15%) women underwent radical vaginal trachelectomy with laparoscopic lymphadenectomy (9--FIGO IA2 and 3--FIGO lB1). Cervical cerciage was performed in all patients after trachelectomy. RESULTS: A total of 52 (76.5%) women after surgical conization successfully conceived. Out of them, 3 (5.8)% women miscarried (1 before 12 and 2 between 12 22 weeks of gestation), 2 (3.8%) delivered pre-term (at 26 and 34 weeks of gestation), and 47 (90.4%) delivered at term, including 5 (10.2%) cesarean deliveries, 1 (2.0%) vaginal delivery with the use of the Bracht Manoeuve; and 43 (87.8%) normal vaginal deliveries. Six (50.0%) women after radical vaginal trachelectomy successfully conceived. Out of them, 1 (16.7%) woman miscarried (at 19 weeks of gestation), 2 (33.3%) delivered pre-term (between 22-32 weeks of gestation), and 3 (50%) delivered at term, including 1 (20%) vaginal delivery at 25 weeks of gestation and 4 (80%) cesarean deliveries (1 at 29 weeks of gestation and 3 at term). CONCLUSIONS: Fertility-sparing surgical management in subjects with early-stage cervical carcinoma, provided the patients have been properly qualified for the procedure, allows a significant number of the affected women to conceive, have a normal pregnancy and delivery PMID- 26665574 TI - Ballantyne Syndrome (Mirror Syndrome) associated with severe non-immune fetal hydrops--a case report. AB - OBJECTIVES: The aim of the study was to present a case of rapidly progressing non immune fetal hydrops (NIHF) of unknown etiology in a normal-karyotype fetus, accompanied by severe maternal edema, anemia, and hypoproteinemia. After the differential diagnosis, Ballantyne Syndrome (BS, Mirror Syndrome) was diagnosed. MATERIAL AND METHODS: We present a case of a 31-year-old multipara at 22/24 weeks of pregnancy presenting severe symptoms of non-immune fetal hydrops: subcutaneous edema, hydrothorax, ascites and placental edema associated with maternal edema, anemia and hypoproteinemia. After cardiovascular infectious, immune and morphological causes were excluded, amniocentesis was performed and confirmed normal female 46, XX karyotype. Since 22 weeks of pregnancy increasing maternal edema and anemia were observed. No hematological, cardiac or nephrological causes of this condition were found. RESULTS: At 24 weeks of pregnancy intrauterine fetal demise was diagnosed and surgical evacuation (cesarean section) of the fetus was performed. Resolution of maternal edema, anemia, and hypoproteinemia was observed shortly after the delivery. CONCLUSIONS: Based on our findings, it seems safe to conclude that BS may develop in pregnancy complicated by NIHF of unknown origin. PMID- 26665575 TI - [Systemic therapy of recurrent or persistent cancer of the cervix. Recommendations of the Polish Gynecological Society]. PMID- 26665576 TI - [Management of Herpes Simplex Virus infection in obstetrics. Recommendations of the Polish Gynecological Society]. PMID- 26665577 TI - DATA Bank. PMID- 26665578 TI - Taking a Second Look at AUDIT DATA. PMID- 26665579 TI - Making Health Data Elegant. PMID- 26665580 TI - ALIGNING COMPUTER-ASSISTED CODING and INFORMATION GOVERNANCE EFFORTS. PMID- 26665581 TI - Ensuring Your Business Associates Provide 'Satisfactory Assurances'. PMID- 26665582 TI - Are You a Data Analyst and Don't Know It? PMID- 26665583 TI - A Decade of Standardization: Data Integrity as a Foundation for Trustworthiness of Clinical Information. PMID- 26665584 TI - Understanding HIM's Impact on Quality at the National Level. PMID- 26665585 TI - Data Quality Management Model (Updated). PMID- 26665586 TI - More Specific Physician Documentation Needed for ICD-10-CM. PMID- 26665587 TI - Building Clarity on the Two-Midnight Rule. PMID- 26665588 TI - A Forty-Year Odyssey in the Sea of Translational Medicine. PMID- 26665589 TI - PAUL MEAD DOTY, 1 JUNE 1920 - 5 DECEMBER 2011. PMID- 26665590 TI - R. DUNCAN LUCE, 16 MAY 1925 - 11 AUGUST 2012. PMID- 26665591 TI - C. EVERETT KOOP, 14 OCTOBER 1916 - 25 FEBRUARY 2013. PMID- 26665592 TI - [Advances in microbial solar cells--A review]. AB - The energy crisis has become one of the major problems hindering the development of the world. The emergence of microbial fuel cells provides a new solution to the energy crisis. Microbial solar cells, integrating photosynthetic organisms such as plants and microalgae into microbial fuel cells, can convert solar energy into electrical energy. Microbial solar cell has steady electric energy, and broad application prospects in wastewater treatment, biodiesel processing and intermediate metabolites production. Here we reviewed recent progress of microbial solar cells from the perspective of the role of photosynthetic organisms in microbial fuel cells, based on a vast amount of literature, and discussed their advantages and deficiency. At last, brief analysis of the facing problems and research needs of microbial fuel cells are undertaken. This work was expected to be beneficial for the application of the microbial solar cells technology. PMID- 26665593 TI - [Signal transduction and drug resistance in Mycobacterium tuberculosis--A review]. AB - Mycobacterium tuberculosis infection kills two million people every year, and the chemotherapy has led to significant amount of drug resistance. Signal transduction systems are used by bacteria to survive or adapt to their living environment, but the relationship to drug resistance is not well understood. In this article, we introduced the two-component signal transduction systems of M. tuberculosis and analyzed their relationship with drug resistance. We identified five two-component system pairs involved in the formation of drug resistance. Therefore, these two-component systems are good targeting sites for small biochemical drugs to target so as to reverse the drug resistance and virulence. PMID- 26665594 TI - [Research progress of Ochrobactrum anthropic--A review]. AB - Ochrobactrum anthropi is a gram-negative bacillus, usually known as an opportunistic pathogen. Mostly its infection is related with systemic or local lower immunity, and manifested as bacteremia, meningitis, purulent infection. Recently, along with expanded infection, it has become an important human pathogen. The prevention, clinical diagnose and treatment become complicated because varied clinical symptoms increased antibiotic resistance and cross immune reaction with others pathogens. In this review, we summarized the biological characteristics, differential diagnosis, immunity, resistance and genomic characteristics of Ochrobactrum anthropi, to provide reference for prevention, control and treatment management of this disease. PMID- 26665595 TI - [Relationship between hepatitis C virus and the transcription coactivator PGC 1alpha--A review]. AB - Approximately 185 million people are or have been infected with Hepatitis C virus ( HCV) worldwide. HCV causes not only severe liver problems but also extra hepatic manifestations, such as insulin resistance (IR) and type 2 diabetes mellitus (T2DM) . Peroxisome proliferator-activated receptor gamma coactivator 1 alpha ( PGC-1alpha) is a transcription factor coactivator that plays an essential role in cellular energy metabolism, and cumulative studies link the abnormal high expression of PGC-1alpha to IR and T2DM. Besides, HCV hijacks host lipid metabolism for its infection, and the very low density lipoprotein (VLDL) secretory pathway is exploited to facilitate HCV assembly and secretion; coincidently, PGC-1alpha is reportedly important in VLDL assembly through a downstream factor. Therefore, we hypothesize that, on the one hand, HCV infection results in WT-PGC-1alpha/L-PGC-1alpha high expression which will further lead to T2DM, on the other hand, WT-PGC-1alpha and L-PGC-1alpha demonstrate proviral functions in HCV production through the regulation of VLDL. Combining previous studies in the literature with our current findings, we elaborate the relationship between HCV and PGC-1alpha, and discuss the mechanism how HCV infection upregulates PGC-1alpha. PMID- 26665596 TI - [Identification and characterization of a hypothermia nitrite bacterium Pseudomonas tolaasii Y-11]. AB - OBJECTIVE: Denitrifying bacteria play an important role in the biological nitrogen removal process. However, there are few studies about hypothermia nitrite denitrifying bacteria. We isolated a hypothermia and aerobic nitrite denitrifying bacterium (named as Y-11) from the long-term flooded paddy soil. Aims of this paper were to clarify the phylogeny and denitrifying characteristics of strain Y-11. METHODS: Morphological observation, specific phospholipid fatty acid and 16S rRNA analysis were employed to identify strain Y-11. Denitrification characteristics of strain Y-11, such as temperature, shaking speed, initial pH and carbon source were investigated by using shaking culture in Erlenmeyer flask. RESULTS: Strain Y-11 with high removal efficiency of nitrite and total nitrogen was identified as Pseudomonas tolaasii. The optimum conditions of Y-11 effectively removing nitrite nitrogen and total nitrogen were: initial pH7.0; 15 degrees C; shaking speed 200 r/min; inoculum size 1.5 x 10(8) CFU per 100 mL medium; sodium acetate as carbon source; and nitrite nitrogen 10 mg/L. Strain Y 11 can remove nitrite nitrogen and total nitrogen up to 100% and 61.28% within 48 h. CONCLUSION: Strain Y-11 was identified as Pseudomonas tolaasii with its potential nitrite polluted water treatment during early winter and late spring. PMID- 26665597 TI - [Screening and functional properties of cholesterol-degrading lactic acid bacteria from Jiangshui]. AB - OBJECTIVE: We intended to obtain and characterize lactic acid bacteria with high capacity of cholesterol-degrading. METHODS: We chose Jiangshui as the experimental material, screened lactic acid bacteria by the culture medium with high cholesterol, and studied other features of lactic acid bacteria like salt tolerant, acid resistance, then identified the species of lactic acid bacteria by combining physiological and biochemical methods and 16S rDNA sequence. RESULTS: All lactic acid bacteria isolated had the capacity of cholesterol-degrading to some extent. There were 4 strains had high cholesterol-degrading rate (> 75%). Four strains were Lactococcus lactis subsp. lactis, two were Brevibacterium casei, and one was Lactococcus raffinolactis. CONCLUSION: Cholesterol-degrading lactic acid bacteria were screened from Jiangshui, with application potential for cholesterol degradation. PMID- 26665598 TI - [Regulation of rsc1285 gene in type III secretion system in Ralstonia solanacearum]. AB - OBJECTIVE: Rsc1285 is one of the putative T3SS-regulated factors in Ralstonia solanacearum, and the regulation of Rsc1285 on T3SS and pathogenicity was characterized. METHODS: The rsc1285 deletion mutants were constructed by homologous recombination and characterized by complementation. RESULTS: The rsc1285 mutant was significantly less virulent than the wild-type strain to infect tomato plants. Rsc1285 controls the expression of hrpB and HrpB-regulating genes, but it is dispensable for the expression of hrpG and prhG. CONCLUSION: R. solanacearum uses Rsc1285 to control the T3SS and pathogenicity via a novel pathway, and this finding provides insights into overall infection mode of R. solanacearum. PMID- 26665599 TI - [Proteomic analysis of curdlan-producing Agrobacterium sp. ATCC 31749 in response to dissolved oxygen]. AB - OBJECTIVE: Curdlan is produced by Agrobacterium sp. ATCC 31749 under nitrogen limiting condition. The biosynthesis of crudlan is a typical aerobic bioprocess, and the production of curdlan would be severely restricted under micro-aerobic and anoxic conditions. Proteomic analysis of Agrobacterium sp. was conducted to investigate the effect of dissolved oxygen on the crucial enzymes involved in curdlan biosynthesis. METHODS: Two-dimensional gel electrophoresis was performed to separate and visualize the differential expression of the intracellular proteins extracted from Agrobacterium sp. ATCC 31749 cultured under various dissolved oxygen levels (75%, 50%, 25% and 5%). In addition, a comparative proteomic analysis of the intracellular proteins expression level under various dissolved oxygen levels was done. Significant differently expressed proteins were identified by MALDI-TOF/TOF. RESULTS: Finally, we identified 15 differently expressed proteins involved in polysaccharide synthesis, fatty acid synthesis, amino acid synthesis pathway. Among these proteins, phosphoglucomutase and orotidine 5-phosphate decarboxylase were the key metabolic enzymes directing curdlan biosynthesis. CONCLUSION: Oxygen could affect the expression of the proteins taking charge of curdlan synthesis significantly. PMID- 26665600 TI - [Physiological and metabolic characteristics of five xylose utilizing yeasts]. AB - OBJECTIVE: It is of great significance to improve the utilization of lignocellulosic material, the most abundant renewable resource on earth. METHODS: We studied the stress tolerance (temperature, ethanol and osmotic tolerance) of five xylose utilizing yeasts, Scheffersomyces stipitis, Candida tenuis, Spathaspora passalidarum, Candida amazonensis and Candida jeffriesii. We also tested their utilization ability of multiple carbon and nitrogen sources. RESULTS: S. passalidarum could tolerate at 44 degrees C and utilize various carbon and nitrogen sources effectively. S. passalidarum could metabolism xylose rapidly to produce ethanol, with an ethanol yield of 0.43 g/g under oxygen limiting condition. C. amazonensis could also torelate at 42 degrees C. Moreover, C. amazonensis could converse xylose to xylitol with ethanol as the main by product. CONCLUSION: S. passalidarum is a potentially valuable workhorse in industrial utilization of lignocellulosic for its excellent characteristics. In addition, C. amazonensis may be a promising xylitol producer. PMID- 26665601 TI - [Cloning, expression, purification and characterization of two uracil-DNA glycosylases from Sulfolobus acidocaldarius]. AB - OBJECTIVE: To characterize uracil-DNA glycosylase from acidophilic and thermophilic Sulfolobus acidocaldarius. METHODS: We cloned udgIV and udgV genes from S. acidocaldarius, expressed the two recombinant UDG proteins in E. coli species BL21 (DE3) Rosetta-pLysS, purified the recombinant UDGs and characterized the removal of dU by UDGs. RESULTS: We successfully expressed two S. acidocaldarius UDGs and found both UDGs having the activity of dU removal. In comparison to UDGV, UDGIV was more efficient in dU removal, with a 750 foldactivity. CONCLUSION: In comparison to UDGV, UDGIV from S. acidocaldarius was a more efficient enzyme responsible for the removal of dU from DNA in vitro. PMID- 26665602 TI - [Purification, identification and characterization of an endoglucanase Egn20 from Fusarium sp. Q7-31T]. AB - OBJECTIVE: The endoglucanase from Fusarium sp. Q7-31T was isolated, purified, identified and characterized to provide data for enzyme system of Fusarium sp. . [Methods] Strain was cultured in liquid fermentation with oat straw as carbon source, the endoglucanase was purified by using Sephacry S-100 chromatography and DEAE-sepharose ion-exchange column chromatography and the enzymatic properties were studied. The protein was identified using MADIL-TOF-TOF. RESULTS: An endoglucanase was purified and named Egn20. The molecular weight was 55.37 kDa and isoelectric point (pI) was 7.44. Egn20 had optimal activity with carboxymethyl cellulose at 40 degrees C and pH 6.0, stabilized at 45 degrees C and pH 5.0 - 7.0, activated by Fe2+, inhibited by Na+, Ca2+, Mg2+, Zn2+, K+ and inactivated by Hg2+. The enzymatic properties and MADIL-TOF-TOF results suggested that Egn20 belongs to GH7 family. CONCLUSION: Our results may provide important data for the study of Fusarium sp. enzyme system. PMID- 26665603 TI - [Association of bacterial diversity in city area of Nanming river with environmental factors]. AB - OBJECTIVE: The aim of this study was to analyze the bacterial diversity of urban section of Nanming river as well as to study relationship between the bacterial diversity and environmental factors. METHODS: The high throughput sequencing on PCR-amplified 16S rDNA V4 fragments was used to determine the bacterial diversity of samples from five sites of Nanming river. The ordination technique of redundancy analysis was used to analyze the effects of the environmental factors on bacterial community composition. RESULTS: Diversity index analysis of bacterial community composition in Nanming river showed that the Shannon-Wiener index of bacterial diversity in Nanmng River was about 7.5. The Shannon-Wiener index of 5 sampling site had an order as Wudang bridge > Shuikou Si > Wuyan bridge > Huaxi bridge > Guanzhou bridge. Based on the sequencing results, there were 11 phyla (327 genera) in the samples, of which proteobacterice (66.1% +/- 3.30% ) was the dominant phyla, Gamma proteobacteria (54.76% +/- 4.86%) was the dominant subgroup and Pseudomonas (16.92% +/- 0.02%) was the dominant genera. In addition, there are some flora and rare flora undetermined. The result of RDA suggested that the influence of different environmental factors on different microbes were different. Bacterial community IV had significant positive correlation with total nitrogen and total phosphorus in the environment. CONCLUSION: This research provides references for the association of bacterial composition and diversity with environmental factors. PMID- 26665604 TI - [Improving thermal stability of Geobacillus sp. ZH1 carboxylesterase by error prone PCR]. AB - OBJECTIVE: This study was aimed to improve the thermal stability of carboxylesterase from Geobacillus sp. ZH1 by directed evolution. METHODS: A library of carboxylesterase mutants was constructed by introducing random mutagenesis using error-prone PCR to screen mutant enzymes with improved thermostability. After induction, expression and purification, the mutant enzyme was characterized. RESULTS: After screening, one mutant strain 65 was obtained with improved carboxylesterase thermal stability. Sequence analysis revealed two amino acid substitutions, including T113S and M160K. According to homologous modeling, T113S was located on the fifth beta-sheet. Another mutant site M160K was located on a loop between the fifth and the sixth alpha-helix, being on the surface of the mutant enzyme. The mutated Lys160 formed an extra hydrogen bond with nearby Thr162. The half-life of mutant enzyme 65 and the parent enzyme at 90 degrees C was 3.1 h and 1.9 h, respectively. The mutant enzyme 65 had a better thermal stability than the parent enzyme. CONCLUSION: Directed evolution by error prone PCR of Geobacillus sp. ZH1 carboxylesterase gene is effective to improve the thermal stability. PMID- 26665605 TI - [Optimization of labeling and localizing bacterial membrane and nucleus with FM4 64 and Hoechst dyes]. AB - OBJECTIVE: To observe cell membrane and nucleus in bacteria for subcellular localization. METHODS: FM4-64 and Hoechst were dyed that can label cell membrane and nucleus, respectively. Both dyes were used to co-stain the membranes and nucleus of eight bacterial strains ( Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Yersinia pestis, Legionella pneumonia, Vibrio cholerae and Bacillus anthracis). E. coli was dyed with different dye concentrations and times and then observed by confocal fluorescence microscopic imaging. RESULTS: Fluorescence intensity of cell membrane and nucleus is affected by dye concentrations and times. The optimal conditions were determined as follows: staining cell membrane with 20 MUg/mL FM4-64 for 1 min and cell nucleus with 20 MUg/mL Hoechst for 20 min. Gram-negative bacteria were dyed better than gram-positive bacteria with FM4-64dye. CONCLUSION: FM4-64 and Hoechst can be used to stain membrane and nucleus in different types of bacteria. Co staining bacterial membrane and nucleus provides the reference to observe cell structure in prokaryotes for studying subcellular localization. PMID- 26665606 TI - [Biosynthesis of selemium nanobars by Shewallena oneidensis MR-1]. AB - OBJECTIVE: We used Shewallena oneidensis MR-1 to produce selemium (Se) nanobars and studied the influence of Se(IV) concentrations and incubation time on nanobars production. METHODS: We incubated Shewallena oneidensis MR-1 under anaerobic condition with Luria-Bertani (LB) liquid medium containing 0.1, 1.0, 10.0 or 100.0 mmol/L Se (IV) in Na2SeO3, to determine the optimal Se (IV) concentration for bacterial growth. Then, we incubated Shewallena oneidensis MR-1 with the optimal Se (IV) concentration and collected deposits 24 and 72 h after anearobic incubation. We used scanning electron microscopy, energy-dispersive X ray and X-ray diffraction to analyse the deposits. RESULTS: The cross sectional diameter and length of deposits that were produced by Shewallena oneidensis MR-1 after 24 h incubation with 1 mmol/L Se(IV) was around 80 nm and 2-3 MUm, respectively. However, the deposits after 72 h incubation exceeded the size limit of nano material. Furthermore, the energy-dispersive X-ray and the X-ray diffraction spectroscopy confirmed that the deposits were elemental Se. CONCLUSION: This study provides a viable method for the biosynthesis of Se nanoban Shewallena oneidensis MR-1 can produce a large number of Se nanobars at exponential phase under 0.1 mmol/L Se (IV). PMID- 26665608 TI - [Introduction to the JJN special issue; Renal fibrosis]. PMID- 26665609 TI - [Current concept in renal fibrosis]. PMID- 26665610 TI - [Renal fibrosis and anemia]. PMID- 26665611 TI - [Kidney fibrosis and endothelial injury]. PMID- 26665612 TI - [Aging and renal fibrosis]. PMID- 26665613 TI - [Therapeutic approaches targeting fibrosis and hypoxia in the kidney]. PMID- 26665614 TI - [Assessment of chronic kidney disease using functional MRI]. PMID- 26665616 TI - [Successful steroid therapy for indolent myeloma with kidney injury due to direct infiltration of myeloma cells]. AB - A 68-year-old woman visited JA Toride Medical Center with asymptomatic proteinuria. Bence Jones protein-lambda was identified in her serum and urine samples, and subsequent bone marrow aspiration revealed multiple myeloma (MM). Simultaneous renal biopsy showed only minor glomerular abnormality and preserved interstitium. Since the clinical stage was not advanced, aggressive treatment was avoided. During the following six months, her renal function gradually deteriorated with sustained elevation of urine protein and beta2 microglobulin excretion, although other routine blood tests yielded stable results. In contrast to the first renal biopsy, the second biopsy specimen exhibited findings suggestive of inflammatory cell infiltration associated with light chain deposition along the tubular basement membrane. However, her myeloma did not cause symptoms other than mild renal disorder and remained in the category of indolent myeloma. Therefore a moderate dose of steroid therapy according to the regimen of common interstitial nephritis was initiated and her renal function and urinary findings partially recovered. Subsequently, her condition was diagnosed as infiltration of plasma cells with positive lambda-light chain deposition. Since direct infiltration of myeloma cells into the renal interstitium rarely causes renal failure especially at the initial stage, we did not conduct intensive chemotherapy with possible severe side effects. More intensive chemotherapy would have been administered if the patient had suffered from other organ damage. There are no reports of cases in whom steroid alone was effective against multiple myeloma, hence this case is of clinical significance in providing a treatment option for renal dysfunction caused by restricted infiltration of myeloma cells, especially for cases where intensive chemotherapy is contraindicated. PMID- 26665615 TI - [Comparison of benefits to non-dialysis CKD patients between darbepoetin alpha and epoetin beta pegol]. AB - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the mainstay of treatment for renal anemia in chronic kidney disease (CKD) patients. However, the difference in hematopoietic effect between darbepoetin alfa (DA) and continuous erythropoiesis receptor activator (CERA) has remained unclear in non-dialysis CKD patients. Another purpose of this study was to analyze the red blood cells indices under treatment with these two ESAs in ESA-naive CKD patients. METHODS: This study was designed as a multicenter retrospective observational investigation, and included 61 patients receiving DA (group DA) and 36 patients receiving CERA (group CERA) for at least six months. Relative effect of these ESAs was determined by comparing means of the individual monthly average of the area under the curve above the initial level of hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBC) with the trapezoidal rule, which are maintenance ratios. Serial changes in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were also evaluated. RESULTS: No differences were found in the mean ratios of Hb, Hct, and RBC, and maintenance ratios of these parameters. The ratio of MCH in group CERA was decreased compared with that in group DA. Subsequent decrease in MCV was also remarkable in group CERA. CONCLUSIONS: It is speculated that iron demand increased during the administration of CERA, which was suggested by changes in the red cell indices. Reticulocyte indices and iron-related parameters could provide a more detailed explanation and the significance of iron supplementation during administration of CERA should be clarified when compared with other types of ESA. PMID- 26665617 TI - [Heparin-induced thrombocytopenia with pseudo-pulmonary embolism in a patient who was newly introduced to hemodialysis treatment]. AB - Pseudo-pulmonary embolism (PPE) superimposed on heparin-induced thrombocytopenia (HIT) is an important complication in patients undergoing hemodialysis (HD) treatment. We report the clinical profile of an HD patient with acute respiratory distress induced by PPE and HIT. A 67-year-old man with diabetic nephropathy and end-stage renal failure developed congestive heart failure. He was admitted to Kitasato University Hospital. He was introduced to HD treatment using low molecular-weight heparin as an anticoagulant for an HD session on day 1 of admission. On day 11 after admission, he suddenly developed respiratory distress and hypoxia at 30 min after the start of the fifth HD session. The HD session was immediately discontinued, and oxygen inhalation improved his complaints and hypoxia. The platelet count decreased from 220 x 10(9)/L at the start of the HD session to 80 x 10(9)/L at the end of the HD session. We suspected HIT when blood clotting occurred in his hemodialyzer and blood circuit for HD during the HD session on day 12. Chest X-ray, electrocardiogram, echocardiography, and pulmonary microcirculation scintigraphy were normal. Serum analysis was positive for heparin-platelet factor 4 (PF4) antibody. We then diagnosed him with PPE superimposed on HIT. After the anticoagulant agent for HD was changed from low molecular-weight heparin to nafamostat mesilate, his clinical symptoms and thrombocytopenia disappeared. PPE superimposed on HIT appeared approximately 7-10 days after the initial use of heparin for the HD session. PPE also led to acute respiratory distress, blood coagulation in the hemodialyzer and blood circuit for HD, as well as thrombocytopenia with less than a 50% decrease in platelet counts. The prognosis of PEE and HIT is good after discontinuing the use of heparin. PMID- 26665618 TI - "A triumph for nurses and Nursing Times". PMID- 26665619 TI - Clarity after chaos on revalidation. PMID- 26665620 TI - Nurses' fury forces government row back on revalidation delay. PMID- 26665621 TI - Report calls for two lung cancer nurses per trust. PMID- 26665622 TI - International expert questions NHS nursing workforce policies. PMID- 26665623 TI - Gaps persist in hospital training for spotting sepsis. PMID- 26665624 TI - New framework could see 'hybrid' job for district and practice nurses. PMID- 26665625 TI - Role expansion could see HCAs take on admin. PMID- 26665627 TI - Malnutrition drives trust to create food bank. PMID- 26665626 TI - Safeguarding nurse and educator is awarded title of Queen's Nurse. PMID- 26665628 TI - Statins may reduce efficacy of flu vaccine, studies suggest. PMID- 26665629 TI - Dementia drug can delay care home admission. PMID- 26665630 TI - "Use the opportunities that are available to work with NICE". PMID- 26665631 TI - "We must tackle the stigma of age-related hearing loss". PMID- 26665632 TI - Improving hand hygiene after neurological injury. AB - Caring for hands tightened by spasticity after stroke, brain injury or other neurological conditions can be challenging for care staff. Opening and cleaning the hand, managing pressure areas, cutting nails and reducing pain becomes more complex if muscles are tight and short. Hand hygiene is key for staff but literature on patients' hand and nail care is lacking, so specialist education and care planning may be needed to help staff ensure these activities are done well. This article outlines the importance of maintaining patients' hand hygiene, explores the barriers to providing effective care and discusses how they might be overcome. PMID- 26665633 TI - Revalidation: practice-related feedback. AB - Obtaining and reflecting on feedback provides an opportunity for professionals to engage with one another to discuss what good care looks like. The NMC believes that reflecting on feedback will be crucial in helping everyone on the register to analyse the way in which they deliver care, and to help them make small changes to their working practice that could make a big difference to patients. PMID- 26665634 TI - The effect of ageing on health inequalities. AB - The final article in this five-part series on the relationship between sociology and nursing practice discusses age-related health inequalities. Age has a direct influence on individuals' health and wellbeing. From a sociological viewpoint, individuals' health status in old age is a reflection of experiences throughout their lifetime, which means that health inequalities accumulate. PMID- 26665635 TI - Using independent mental health advocates. PMID- 26665636 TI - 60 seconds with Kathryn Burn. PMID- 26665637 TI - Show off your strengths. PMID- 26665638 TI - Editorial. PMID- 26665639 TI - CULTURAL DIVERSITY & INCLUSIVITY. WHERE ARE WE AT? PMID- 26665640 TI - Refining your art and maintaining enthusiasm for nursing--The role of Reflective Clinical Supervision. PMID- 26665641 TI - Weeding out fake and rogue practitioners--a duty owed to consumers. PMID- 26665642 TI - Breathing retraining in anxiety and panic disorder. PMID- 26665643 TI - Face to face and person to person: rural clinicians' views on engaging with mental health consumers. PMID- 26665644 TI - Rural and remote tele-assistance for procedural skills: the 'helping hands' project. PMID- 26665645 TI - Improving the physical health of people with schizophrenia in regional Australia. PMID- 26665646 TI - The women's wellness after cancer program: a nurse led model of care. PMID- 26665647 TI - Palliative care experiences in regional NSW. PMID- 26665648 TI - Preparing nurses to practice evidence based suicide prevention skills in the bush. PMID- 26665649 TI - Supporting rural mental health practitioners to practice evidence based care. PMID- 26665650 TI - Why the grass is greener amongst the red dirt. PMID- 26665651 TI - Clinical leadership and nursing. PMID- 26665652 TI - Newborn falls are not a priority. PMID- 26665653 TI - Risking nurses and midwives. PMID- 26665654 TI - Global burden of Non Communicable Diseases. PMID- 26665655 TI - [The comeback of paternalism?]. PMID- 26665656 TI - [Benefits of gluten-free diet: myth or reality?]. AB - Non celiac gluten sensitivity may explain digestive and general symptoms in patients without celiac disease but this recently described entity is controversial. The role of gluten in comparison to other nutriments such as saccharides and polyols (FODMAPs) remains debated. If a gluten-free diet is clearly indicated in celiac disease and wheat allergy, it remains debatable in non-celiac gluten sensitivity given weak and contradictory evidence. There is no strong evidence for a strict indication to a gluten-free diet in endocrinological, psychiatric, and rheumatologic diseases, or to improve performance in elite sports. PMID- 26665657 TI - [Refeeding syndrome: practical issues]. AB - The refeeding syndrome is frequent and potentially deadly, still it is underdiagnosed. It is defined by clinical and biological manifestations that are seen upon refeeding of malnourished patients. It is the consequence of the transition from catabolism to anabolism. Ions intracellular shift caused by insulin and B1 vitamin deficiency are fundamental in the development of this syndrome. Riskconditions are well summarized by the NICE criteria. To avoid refeeding syndrome, it is fundamental to find and correct any electrolytic deficiency and to give thiamine before starting a slow and progressive oral, enteral or parenteral refeeding. PMID- 26665658 TI - [Screening strategies for atrial fibrillation]. AB - The prevalence of AF is increasing and represents a major public health issue. Current guidelines recommend screening with an ECG in all patients >65 years with an irregular pulse. However, single time point screening has a low yield, particularly for silent AF. Silent or infra clinical AF nevertheless carries a thromboembolic risk clinically similar to declared AF The development of continuous heart monitoring devices now enables earlier detection and management of AF. Data demonstrating efficacy of oral anticoagulant in silent AF is lacking, therefore it appears too early to recommend changes to current screening procedures. PMID- 26665659 TI - [Anticoagulation for atrial fibrillation in the patient at risk for falls]. AB - The incidence of atrial fibrillation increases with age as does the risk of subsequent ischemic stroke. Falls are a frequent problem in the geriatric population and often hamper the clinician in prescribing anticoagulants despite an indication based on the CHA2DS2-VASc score for fear of intracranial bleeding. This paper reviews the evidence on the safety of oral anticoagulants in this population. Based on observational data, being at risk for falls does not appear to be an absolute contraindication to oral anticoagulants. PMID- 26665660 TI - [Long term aspirin in stable coronary disease with an indication for anticoagulation: is it reasonable?]. AB - In patients with both stable coronary disease and atrial fibrillation, a baseline treatment of aspirin and an oral anticoagulant is often prescribed due to the proven benefits of each therapy on cardiovascular and thromboembolic events and mortality. However, recent cohort studies in this population have shown that adding aspirin to an oral anticoagulant is not associated with a reduction in recurrence of coronary or thromboembolic events, but significantly increases the bleeding risk. In these patients, in particular when their bleeding risk is high, aspirin withdrawal may be considered. PMID- 26665661 TI - [Generic and biosimilar drug substitution: a panacea?]. AB - Drugs are the third largest source of expenditure under Switzerland's compulsory basic health insurance. Generics, the price of which should be at least 30 per cent less than the cost of the original drugs, can potentially allow substantial savings. Their approval requires bioequivalence studies and their use is safe, although some factors may influence patients' and physicians' acceptance. The increased substitution of biosimilar drugs for more expensive biotech drugs should allow further cost savings. In an attempt to extend the monopoly granted by the original drug patent, some pharmaceutical companies implement "evergreening" strategies including small modifications of the original substance for which the clinical benefit is not always demonstrated. PMID- 26665662 TI - [Clinical gait analysis: user guide]. AB - Clinical gait analysis has become an indispensable medical examination for the management of patients with complex gait disorders. As its name suggests, the purpose of this examination is to assess patients whilst they are walking in a laboratory setting. Measurements include: 3 dimensional joint motion, forces applied to joints, and electromyographic muscle activity. This quantitative data allows identification of walking deviations and to deduce the likely causes of these deviations thanks to the clinical data available for each patient. PMID- 26665663 TI - [2015: the Nobel jury reveals research against parasitic diseases]. PMID- 26665664 TI - [Humanity will be destroyed because we do not like the bad news?]. PMID- 26665665 TI - [Helicobacter pylori infection: bacterial resistance forces a change of gun]. PMID- 26665666 TI - [Work, it is good for health...or not]. PMID- 26665667 TI - [The whiteness of the gene, the scare of the racist]. PMID- 26665668 TI - [Grand maneuvers around the training of physicians]. PMID- 26665669 TI - [Neuchatel: new hospital list in the form of status quo]. PMID- 26665670 TI - [The revolt of the robots]. PMID- 26665671 TI - [Lumbar disc herniation and andrological diseases]. AB - Lumbar disc herniation is a common male disease. In the past, More academic attention was directed to its relationship with lumbago and leg pain than to its association with andrological diseases. Studies show that central lumber intervertebral disc herniation may cause cauda equina injury and result in premature ejaculation, erectile dysfunction, chronic pelvic pain syndrome, priapism, and emission. This article presents an overview on the correlation between central lumbar intervertebral disc herniation and andrological diseases, focusing on the aspects of etiology, pathology, and clinical progress, hoping to invite more attention from andrological and osteological clinicians. PMID- 26665672 TI - [Expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction]. AB - OBJECTIVE: To study the expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction (ED). METHODS: We established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol (DES) and treated the control rats with normal saline (n = 10) or sterilized arachis oil (n = 10). After 8 weeks, we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin (PRL) and testosterone (T) to confirm the successful construction of the prolactinoma-induced ED model. Then we determined the expression of nNOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope. RESULTS: The prolactinoma-induced ED model was successfully established in 15 rats. The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls ([46.7 +/- 15.5] vs [11.7 +/- 2.4] and [12.4 +/- 2.3] mg, both P < 0.05). The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups ([1,744.9 +/- 304.5] vs [11.5 +/- 2.4] and [10.6 +/- 1.9] ng/ml, both P < 0.0l; [1.54 +/- 0.46] vs [3.11 +/- 1.08] and [3.04 +/- 1.11] ng/ml, both P < 0.05). The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls (16.7% vs 100% and 87.5%, both P < 0.05), and so was the expression of nNOS in the penile tissue (0.024 +/- 0.011 vs 0.066 +/- 0.019 and 0.058 +/- 0.021, both P < 0.05). Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models. CONCLUSION: The ultrastructural changes of the penile cavernous tissue and the reduced expression of nNOS in penile tissue may be the most important mechanisms of prolactinoma-induced ED in rats. PMID- 26665673 TI - [Blood vessels and nerves surrounding the seminal vesicles: A clinical anatomic study]. AB - OBJECTIVE: To investigate the precise locations of the blood vessels and nerves surrounding the seminal vesicles (SV) in men and provide some anatomical evidence for SV-related minimally invasive surgery. METHODS: We observed the courses and distribution of the blood vessels and nerves surrounding SVs and obtained the data for positioning the SV neuroplexes in 20 male pelvises. RESULTS: One branch of the neuroplexes was distributed to the SVs bilaterally with the neurovascular bundles, (2.85 +/- 0.18) cm from the median sulcus of the prostate (MSP), while another branch ran through the Denonvillier fascia behind the SV, (0.81 +/- 0.06) cm from the MSP. The arterial SVs (ASV) originated from the inferior vesical artery and fell into 4 types, 55% going directly to the SVs as one branch, 15% running between the SV and the ampulla of the deferent duct as another branch, 25% downward as 2 branches to the SV and between the SV and the ampulla of the deferent duct respectively, and 5% as the other ASVs. The shortest distance from the ASV through the prostatic neuroplexus to the posterior SV was (1.08 +/- 0.09) cm. CONCLUSION: In SV resection, neuroplexus injury can be reduced with a bilateral distance of < 2.85 cm and a posterior distance of < 0.81 cm from the MSP, and so can bleeding by vascular ligation between the SV and the ampulla of the deferent duct. PMID- 26665674 TI - [Spermatozoal immobilization ability and virulence genes of Staphylococcus aureus isolated from the semen of infertile men]. AB - OBJECTIVE: To investigate the impact of Staphylococcus aureus from infertile men on sperm motility and the relationship between virulence genes and the activity of spermatozoal immobilization. METHODS: We collected 60 strains of non-repeated Staphylococcus aureus from the semen of 589 infertile males and analyzed the influence of Staphylococcus aureus on sperm motility using the computer-aided sperm analysis system. We selected the strains that apparently decreased sperm motility and detected their virulence genes by PCR. RESULTS: Sperm motility was significantly decreased in 17 of the 60 strains of Staphylococcus aureus (P < 0.05). The main virulence genes in these strains were hlg (33.3%), scn (23.3%), cna (20%), hlb (20%), and clfA (18.3%), others including icaA, fnbA, tst, seb, hld, eta and sea. The scn gene carriers accounted for 47.1% in the spermatozal immobilization positive group, significantly higher than 14% in the negative group (P < 0.05). No statistically significant differences were found in the percentages of the carriers of the other virulence genes between the two groups (P > 0.05). CONCLUSION: Infections of Staphylococcus aureus in male reproductive system can lead to the decrease of sperm motility, which may be associated with the Staphylococcus complement inhibitor encoding gene scn. PMID- 26665675 TI - [Relationship between TMPRSS2: ERG and the pathological grade of prostate cancer]. AB - OBJECTIVE: To study the relationship between TMPRSS2: ERG gene fusion and the pathological grade of prostate cancer (PCa). METHODS: We collected fresh prostatic tissue samples from 62 patients with PCa and another 10 with benign prostatic hyperplasia ( BPH) and included 9 cancer cell strains as the control. We examined the TMPRSS2:ERG fusion gene in the PCa samples by nest RT-PCR, compared the Gleason scores between the TMPRSS2:ERG-positive and -negative cases, and analyzed the association of TMPRSS2: ERG fusion with the pathological features of PCa. RESULTS: The TMPRSS2: ERG fusion gene was detected in 28 (45.16%) of the PCa cases, but in none of the 10 BPH cases or the 9 cancer cell strains. No statistically significant differences were found in the Gleason scores between the TMPRSS2:ERG-positive and -negative cases (Z = -0.609, P = 0.542), but the primary Gleason score was markedly higher in the former than in the latter (Z = -2.600, P = 0.009). Univariate logistic regression analysis showed that TMPRSS2:ERG was associated with the cribriform growth pattern (OR = 6.250, P = 0.002), foamy gland morphology (OR = 6.666, P = 0.023), and signet ring cells (OR = 3.240, P = 0.035), but multivariate logistic regression analysis manifested that it was associated with the cribriform growth pattern only (OR = 3.750, P = 0.033). CONCLUSION: TMPRSS2:ERG gene fusion was associated with higher pathological grades of prostate cancer. PMID- 26665676 TI - [Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation]. AB - OBJECTIVE: To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS: We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS: IELT was significantly increased in both the dapoxetine (from [0.87 +/- 0.31] to [2.84 +/- 0.68] min, P < 0.05) and the sertraline group (from [0.84 +/- 0.28] to [2.71 +/- 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION: On-demand oral medication of dapoxetine is effective and well tolerated for the treatment of premature ejaculation. PMID- 26665677 TI - [Transurethral transumbilical laparoendoscopic single-site surgery for radical prostatectomy]. AB - OBJECTIVE: To investigate the feasibility and advantages of transurethral transumbilical laparoendoscopic single-site surgery (TU-LESS) for radical prostatectomy. METHODS: Five patients with prostate cancer underwent TU-LESS for radical prostatectomy, with a four-channel single-port device inserted into a 2. 5 cm periumbilical incision and another placed through the urethra, followed by analysis of the perioperative data. RESULTS: All the operations were successfully accomplished, with neither conversion to open surgery nor additional channel. The mean operation time, intraoperative blood loss, and postoperative hospital stay were 168 min, 120 ml, and 15 d, respectively. No severe perioperative complications were observed. TNM stage classification manifested T2cN0M0 in 2 cases and T2bN0M0 in the other 3. Postoperative pathology showed no negative surgical margins in any of the cases. CONCLUSION: TU-LESS is safe and feasible for radical prostatectomy and can reduce the complication of low urinary tract surgery by single-site laparoendoscopy. PMID- 26665678 TI - [Prostatic arterial embolization for benign prostatic hyperplasia in high-risk aged males]. AB - OBJECTIVE: To explore the efficacy and safety of prostatic arterial embolization (PAE) in the treatment of benign prostatic hyperplasia ( BPH) in high-risk aged males. METHODS: We retrospectively analyzed the clinical data about 21 high-risk BPH patients aged 77-91 (mean 80) years treated by PAE. RESULTS: PAE was successfully performed in all the 21 patients, with the operation time of 90-120 min. At 2 weeks, 3 months, 6 months, and 12 months after surgery, the International Prostate Symptom Scores (IPSS) were 18.3 +/- 3.1, 9.8 +/- 2.7, 9.4 +/- 2.5, and 10.1 +/- 2.2, the quality of life scores ( QOL) were 4.6 +/- 1.4, 4.3 +/- 1.2, 4.6 +/- 1.1, and 4.9 +/- 0.6, the maximum urinary flow rates ( Qmax) were (12.5 +/- 2.5), (15.8 +/- 2.4), (16.6 +/- 2.2), and (16.3 +/- 1.8) ml/s, and the postvoid residual urine volumes (PVR) were (35.0 +/- 3.4), (13.0 +/- 3.3), (10.0 +/- 3.0), and (8.0 +/- 2.5) ml, respectively, markedly improved as compared with the baseline (IPSS: 24.5 +/- 3.7, QOL: 5.7 +/- 1.6, Qmax: [8.3 +/- 2.1] ml/s, and PVR: [98.0 +/- 11.0] ml), with statistically significant differences in IPSS, QOL, Qmax, and PVR (all P < 0.05). The maximal velocity of blood flow in the prostate was obviously decreased and the prostate volumes were (74.4 +/- 4.8), (42.5 +/- 4.4), (38.3 +/- 4.0), and (36.7 +/- 3.5) cm3 at 2 weeks, 3 months, 6 months, and 12 months, respectively, also significantly reduced in comparison with (84.3 +/- 5.4) cm3 preoperatively (all P < 0.05). CONCLUSION: PAE is a safe and effective option for the treatment of BPH in high-risk aged males. PMID- 26665679 TI - [3D versus 2D laparoscopic radical prostatectomy for the treatment of prostate cancer]. AB - OBJECTIVE: To compare the outcomes and complications of 3D versus 2D laparoscopic radical prostatectomy ( LRP) in the treatment of prostate cancer. METHODS: We retrospectively reviewed 18 cases of prostate cancer treated by 3D LRP and another 32 by 2D LRP. We compared the general data, intraoperative blood loss, postoperative drainage time and hospital stay, Gleason scores, and incidence of complications between the two groups of patients. RESULTS: All the operations were successful and none was transferred to open surgery. The two groups of patients were similar in terms of age, body mass index, Gleason scores, and clinical stages. However, compared with the 2D LRP group, the 3D LRP group showed significantly shorter operation time ([180.2 +/- 69.1] vs [118.3 +/- 55.1] min, P < 0.01), less blood loss ([236.5 +/- 60.6] vs [89.1 +/- 35.2] ml, P < 0.01), less postoperative drainage time ([7.1 +/- 1.1] vs [5.3 +/- 2.1] d, P < 0.01), shorter postoperative hospital stay ([20.2 +/- 5.5] vs [14.4 +/- 7.2] d, P < 0.01), and lower incidence of perioperative complications (3.1% vs 0, P < 0.01). The incisal margin was pathologically negative in both groups and urinary incontinence was found in neither at 6 months after surgery (P > 0.05). CONCLUSION: 3D LRP, with its advantages of shorter operative time, faster recovery, and better outcomes than 2D LRP in the treatment of prostate cancer, deserves general application in lower-level hospitals. PMID- 26665680 TI - [Application value of Provider-Initiated HIV Testing and Counseling in dermatology]. AB - OBJECTIVE: To explore the clinical application value of Provider-Initiated HIV Testing and Counseling (PITC) by analyzing the positive rate of HIV tests for people in need of PITC and that of routine HIV tests. METHODS: We retrospectively analyzed the demographic and epidemiologic data about the patients seeking PITC services or undergoing routine HIV tests in Nanjing Drum Tower Hospital between January and December 2013. RESULTS: The positive rate of initial HIV screening was 1.98% in the PITC group and 0.24% in the routine test group, while that of confirmed HIV was 0. 40% in the former and 0.07% in the latter, both with statistically significant differences between the two groups (P < 0.01). The positive rate of HIV was markedly higher in males than in females, particularly in the PITC group. CONCLUSION: PITC has a high clinical value in HIV detection for targeted subjects and therefore deserves general application in dermatology. PMID- 26665681 TI - [Association of fertilization strategy and embryo transfer time with the incidence of ectopic pregnancy]. AB - OBJECTIVE: To investigate the correlation of the fertilization strategy and embryo transfer (ET) time with the incidence of ectopic pregnancy. METHODS: We selected 3,331 fresh and 2,706 frozen-thawed ET cycles for the patients undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The fresh transfers included 2 546 IVF-ET and 785 ICSI-ET cycles and 2,220 day-3 embryo and 1,111 day-5 blastocyst transfers, while the frozen-thawed transfers included 2,080 IVF-ET and 626 ICSI-ET cycles and 741 day-3 embryo and 1 965 day-5 or -6 blastocyst transfers. We compared the incidence rate of ectopic pregnancy associated with different fertilization strategies and ET time. RESULTS: The incidence rate of ectopic pregnancy was 1. 41% (36/2 546) in the IVF ET cycles and 3.44% (27/785) in the ICSI-ET cycles of the fresh transfers, significantly lower in the IVF-ET than in the ICSI-ET cycles (P < 0.01), and it was 1.01% (21/2,080) in the IVF-ET cycles and 0.80% (5/626) in the ICSI-ET cycles of the frozen-thawed transfers, with no remarkable difference between the two groups (P > 0.05). The IVF-ET and ICSI-ET cycles included 2,220 fresh day-3 (F D3) embryos, 1,111 F-D5 blastocysts, 741 frozen-thawed day-3 (T-D3) embryos, and 1,965 T-D5/6 blastocysts. The incidence rate of ectopic pregnancy was 1.71% (n = 38) in the F-D3, 2.25% (n = 25) in the F-D5, 1.35% (n = 10) in the T-D3, and 0.81% (n = 16) in the T-D5/6 group, respectively, significantly lower in the T D5/6 than in the other three groups (P < 0.05). CONCLUSION: The incidence rate of ectopic pregnancy is associated with fertilization strategies, which is significantly lower in frozen-thawed than in fresh embryo transfers. PMID- 26665682 TI - [Diagnosis and treatment of ovotesticular disorder of sex development: A report of 2 cases]. AB - OBJECTIVE: To investigate the characteristics, diagnosis, and treatment of ovotesticular disorder of sex development (OT-DSD). METHODS: We retrospectively analyzed 2 cases of OT-DSD treated in our hospital. The patients were 19 and 15 years old, respectively, and both received systematic physical examination and examinations of the karyotype, sex hormone, adrenocorticotropic hormone (ACTH), color Doppler ultrasonography, urethrocystoscopy, and human chorionic gonadotropin (HCG) test. Under the laparoscope, we performed surgical gonad exploration, gonadectomy, and vulvar orthopedics. Intraoperative exploration and pathology confirmed true hermaphroditism in both cases, with sex selection as female. One underwent laparoscopic resection of the ovotestis, and the other removal of the testis with the ovarian tissue reserved. RESULTS: The patients were followed up for 12 months postoperatively, which found no abnormality in either the vulvas or the genital glands. CONCLUSION: Surgical exploration of the gonad is the only method for the diagnosis of OT-DSD and sex selection is the key to treatment. Laparoscopic surgical exploration of the gonad and vulvar orthopedics are the first treatment options. PMID- 26665683 TI - [Clinical efficacy of Paroxetine combined with mid-frequency electrical pulse acupoint stimulation for premature ejaculation]. AB - OBJECTIVE: To investigate the clinical value of Paroxetine combined with mid frequency electrical pulse acupoint stimulation (EPAS) in the treatment of premature ejaculation (PE). METHODS: Totally 69 PE patients were equally assigned to receive oral Paroxetine 20 mg/d, mid-frequency EPAS, or oral Paroxetine 10 mg/d combined with mid-frequency EPAS (P + EPAS) , all for 8 weeks. We obtained the intravaginal ejaculation latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE-5) scores of the patients before and after treatment, and compared adverse reactions among the three groups of patients. RESULTS: One patient of the Paroxetine group gave up treatment because of abdominal pain and nausea. Compared with the baseline, the patients in the Paroxetine, EPAS, and P + EPAS groups all showed markedly increased IELT ([0.92 +/- 0.11] vs [4.07 +/- 0.11] min, P < 0.01; [0.92 +/- 0.12] VS [2.78 +/- 0.17] min P < 0.05; [0.91 +/- 0.09] vs [5.31 +/- 0.13], P < 0.01) and decreased CIPE-5 scores (12.5 +/- 3.0 vs 22.0 +/- 2.1, P < 0.01; 12.8 +/- 2.9 vs 19.5 +/- 1.9, P > 0.05; 13.1 +/- 2.8 vs 25.2 +/- 2.1, P 0.01), with statistically significant differences between the P + EPAS group and the other two (P < 0.05). The total effectiveness rate was 95.7% in the P + EPAS group, remarkably higher than in the Paroxetine (72.7%, P < 0.05) and the EPAS group (47.8, P < 0.01). CONCLUSION: Oral Paroxetine combined with mid-frequency EPAS has a higher safety and efficacy than either Paroxetine or EPAS alone in the treatment of PE. PMID- 26665684 TI - [Induced pluripotent stem cells in spermatogenesis: Progress in current studies]. AB - Spermatogenesis is a complex process. Current knowledge about human spermatogenesis is mainly based on the mouse model while little is known about the initial stage of this fundamental process in humans. The establishment of the model of spermatogenesis in vitro may contribute to an overall understanding of male germ cell development, an insight into the mechanisms of infertility, and clinical management of male infertility. This review summarizes current knowledge about the generation of germ cell-like cells from induced pluripotent stem cells (iPSCs) in vitro and discusses the potential application of iPSCs in the treatment of male infertility. PMID- 26665685 TI - [Dapoxetine for premature ejaculation: Advances in clinical studies]. AB - Premature ejaculation (PE) is a most common sexual dysfunction, for which dapoxetine, a novel selective serotonin (5-HT) re-uptake inhibitor (SSRI), is the only licensed oral medicine at present. With the advantages of fast absorption, rapid action, on-demand medication, and short half-life time, dapoxetine has been proved by clinical trials to be effective in prolonging the intravaginal ejaculation latency time (IELT) and improving the overall condition of PE patients in various areas and populations. Compared with the traditional SSRIs, dapoxetine has a better safety and tolerability. The most frequently reported dapoxetine-related adverse events include nausea, diarrhea, headache and dizziness, but with very few severe or serious cases. PMID- 26665686 TI - [Related biomarkers in the diagnosis of prostate cancer]. AB - Prostate cancer is one of the most common malignant tumors in the male urinary system as well as the second leading cause of cancer death in men. Prostate specific antigen (PSA) screening is the main method for the early diagnosis of prostate cancer, but has a low specificity for its detection. In recent years, a variety of tumor markers with high sensitivity and specificity have been found. This review focuses on some of the more promising tumor biomarkers such as prostate cancer antigen 3, early prostate cancer antigen, prostate-specific membrane antigen, alpha-methylacyl-CoA racemase, and vascular endothelial growth factor. PMID- 26665687 TI - [Role of TRAIL in the treatment of prostate cancer: An update]. AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super family found in recent years, which widely exists in the body tissues and participates in the immune regulation, immune stability, and immune surveillance of the human body. The TRAIL receptor is expressed in the surface of a variety of cells. Recent studies show that TRAIL induces the apoptosis of tumor cells and has no significant toxic effect on normal cells. Its anti-tumor activity and safety have been widely recognized. The development of prostate cancer is regulated by the mechanisms of cell apoptosis. TRAIL can induce the apoptosis of prostate cancer cells, and therefore has a great application value in the treatment of prostate cancer. PMID- 26665688 TI - [Aberrant expression of long noncoding RNA in prostate cancer]. AB - Prostate cancer (PCa) is one of the most common malignant tumors as well as a frequent cause of cancer-related mortality in men worldwide. The test of serum markers has dramatically improved the early diagnosis of PCa, but its underlying molecular mechanisms are not yet completely identified. Long noncoding RNA (IncRNA) is emerging as a new player in the PCa paradigm demonstrating its potential roles in both oncogenic and tumor suppressive pathways. LncRNA is frequently aberrantly expressed in the majority of PCa cases. This review highlights recent findings of the aberrant expression of lncRNA in PCa and discusses its novel roles in the diagnosis, prediction, prognosis, metastasis, and potential clinical treatment of PCa. PMID- 26665689 TI - UK's Legalisation of Mitochondrial Donation in IVF Treatment: A Challenge to the International Community or a Promotion of Life-saving Medical Innovation to Be Followed by Others? AB - Mitochondrial DNA diseases are rare genetic disorders, which can have a devastating effect on the patients' health and well-being. There is no cure for such diseases, although recent experiments suggest that there may be a way to prevent them by genetically altering the eggs or embryos through a procedure known as mitochondrial donation. However, such a procedure not only raises serious safety and ethical concerns, but legal challenges as well, since it involves germline gene modification, which until recently was not legal in the UK or elsewhere. In February 2015, the British Parliament amended the relevant legislation to allow such. a procedure, making the UK the first state to openly challenge the global policy on germline gene modification. The article presents the scientific background to the procedure and discusses the regulatory challenges brought by the first case of its legalisation. PMID- 26665690 TI - Encountering Challenges with the EU Regulation on Advance Therapy Medical Products. AB - This article aims at analysing how well the Advanced Therapy Medical Product Regulation (EC) No. 1394/2007 (ATMP Regulation) meets the needs of small and medium-sized enterprises (SMES), academia and public tissue establishments developing advanced therapy medical products (ATMPS). Benefits and shortcomings of the ATMP Regulation are identified, and possible amendments are proposed to accelerate the translation of research into advanced therapies and to facilitate the commercialisation of ATMPS whilst ensuring safety. It was set up as a lex specialis to ensure the free movement of ATMPS within the EU in order to facilitate their access to the internal market and to foster the competitiveness of European pharmaceutical companies, while guaranteeing the highest level protection of public health. Since the adoption of the ATMP Regulation in late 2008, only 5 ATMPS have been granted marketing authorisations thus far. Hence, there is a need to analyse whether the ATMP Regulation meets its objectives. PMID- 26665691 TI - Direct-to-consumer Genetic Testing: Changes in the EU Regulatory Landscape. AB - Rapid advances in genomics and technology have rendered genetic testing services easily accessible to consumers over the Internet in the form of direct-to consumer genetic testing. In the EU, the IVD Directive has been animadverted for its inability to tackle the challenges direct-to-consumer genetic testing has posed. Currently, the EU legislation is in a transition state. It is thus, timely to assess, to what extent the proposed IVD Regulation is intended to address the performance requirements and utility of direct-to-consumer genetic tests, which are made available to consumers within the EU over the Internet, and discuss the developments vis-a-vis the IVD Directive. To compare with the IVD Directive, the IVD Regulation presents a major shift in how direct-to-consumer genetic testing is treated in the E U. It remains unclear, whether and how the EU requirements can be applied beyond the EU market. PMID- 26665692 TI - Physician Specialists' Perceptions of the Medical Malpractice System in Belgium. PMID- 26665693 TI - European Court of Human Rights. ECHR 2015/17 Case of Temchenko v. Ukraine, 16 July 2015, no. 30579/10 (Fifth Section). PMID- 26665694 TI - European Court of Human Rights. ECHR 2015/18 Case of Kuttner v. Austria, 16 July 2015, no. 7997/08 (First Section). PMID- 26665695 TI - European Court of Human Rights. ECHR 2015/19 Case of Bataliny v. Russia, 23 July 2015, no. 10060/07 (First Section). PMID- 26665696 TI - European Court of Human Rights. ECHR 2015/20 Case of Parillo v. Italy, 27 August 2015, no. 46470/11 (Grand Chamber). PMID- 26665697 TI - European Court of Justice. ECJ 2015/6 Abcur AB v. Apoteket Farmaci AB (C-544/13), and Apoteket AB and Apoteket Farmaci AB (C-545/13) of 16 July 2015. PMID- 26665698 TI - Health Effects of Waterborne Contaminants: A Focus on Emerging Concerns. PMID- 26665700 TI - Human Resources as a Strategic Partner. PMID- 26665699 TI - Introduction to the Toxins Special Issue on Ergot Alkaloids. PMID- 26665701 TI - Preventing Contract Violations. AB - Boards must ask tough questions about physician arrangements to ensure compliance with federal laws. PMID- 26665702 TI - THE NEW CEO. AB - Traditional management skills are still crucial when it comes to keeping hospitals and health systems running smoothly, but as health care changes dramatically, boards also must consider "learning agility" and "emotional intelligence" when working with the C-suite. PMID- 26665703 TI - Cybersecurity: The heat is on. AB - Breaches of confidential patient information are proliferating and the culprits are more sophisticated and sinister than ever. Hospitals and health systems are using smarter and faster tactics to stay one step ahead of the bad guys. PMID- 26665704 TI - Preparing for an At-Risk Era. AB - Transitioning to value-based health care is a daunting task, but boards can take steps today to help their hospitals thrive now and into the future. PMID- 26665705 TI - Digital and Social Media Engagement. AB - Understanding the value and potential of social media can help to leverage benefit programs and patient engagement in a way never considered possible. PMID- 26665706 TI - The Power of Humility. AB - Consistently high-performing health systems and hospitals have one key trait in common: humility. PMID- 26665707 TI - Change for the Better. AB - As health care leaders think about replacing board positions, they look for many perspectives. PMID- 26665708 TI - Committing to Population Health. AB - New survey from two American Hospital Association affiliates finds population health is no longer a mission for the ambitious few. PMID- 26665709 TI - CMS Stingier Than It Looks When It Comes to New Treatments. PMID- 26665710 TI - As a killer, cancer catching up to heart disease. PMID- 26665712 TI - 'Can We All Just Get Along?'. PMID- 26665711 TI - Active Surveillance Helped Me Avoid Prostate Surgery For Now. PMID- 26665713 TI - FDA approval of oncology drug indications, 1949-2015. PMID- 26665714 TI - A Rare Approval. FDA OKs Pediatric Cancer Drug. PMID- 26665715 TI - Gains Against Cancer, But Enter 'Financial Toxicity'. PMID- 26665716 TI - Putting Cancer Care on the Right Path. PMID- 26665717 TI - Managing Cancer Care at a Time Of 'Transformational Improvement'. PMID- 26665718 TI - Using Vignettes to Measure and Encourage Adherence to Clinical Pathways in a Quality-Based Oncology Network: An Early Report on the Moffitt Oncology Network Initiative. AB - INTRODUCTION: The Moffitt Oncology Network (MON) Initiative demonstrates a way to form a value-based network based upon clinical pathways across a broad geographical area. METHODS: Moffitt Cancer Center (MCC) has developed various cancer-specific pathways. MCC pathways translate evidence-based guidelines into personalized cancer treatment and set a care standard for evaluation and personalized treatment. MCC is using these pathways with other hospital systems and physician groups throughout the MON. Clinical Performance and Value Vignettes, which are virtual patient cases related to the specific clinical pathways, are used to improve the uptake of pathways in the MON. We report here on the baseline data of 66 breast cancer care providers who took 132 breast cancer vignettes. Using the vignettes, variation in care practice is examined, with special attention to use of clinical breast cancer pathways. RESULTS: Pathway-based clinical care was measured at baseline across MON sites.The mean distributions at baseline varied across all sites and were not statistically significantly different (P>.05). Scores varied by domain across sites, although history and physical scores tended to be higher than work-up, diagnosis, and treatment scores. Pathway adherence also varied for specific diagnostic evaluations or treatments: surgery; sentinel/axillary lymph node dissection; radiation therapy; chemotherapy; and hormonal therapy, and also for the prevalence of unnecessary testing. CONCLUSION: Our study suggests that fostering the adoption of breast cancer clinical pathways into an oncology network is feasible; however, adherence to pathways in breast cancer is varied and reducing such variation is a priority as oncology networks continue to grow in popularity. PMID- 26665719 TI - World, U.S. costs for cancer care to skyrocket by 2030. PMID- 26665721 TI - Anticipating the Changes That Will Touch Us All. PMID- 26665720 TI - Catholic Identity Then and Now. PMID- 26665722 TI - Did Anyone Realize What Was Ahead? Catholic Health Care And Vatican II. PMID- 26665723 TI - To Teach and Heal As Jesus Did. PMID- 26665724 TI - Institutionalizing Catholic Identity. PMID- 26665725 TI - The Leadership Academy And Theological Reflection. PMID- 26665726 TI - Beyond Brand: The Essential Character of Catholic Health Care. PMID- 26665727 TI - Bridging Two Solitudes: Two Faces of the Same Ministry. PMID- 26665728 TI - A 'Lost' Sacrament of The Church: Viaticum. PMID- 26665729 TI - Vatican II's Language Marks Pivotal Shift. PMID- 26665730 TI - OUR CALL: FIND WAYS TO INCREASE ACCESS. PMID- 26665731 TI - A HOLISTIC APPROACH TO THE BUSINESS OF CATHOLIC HEALTH. PMID- 26665732 TI - THEMES OF TRUST AND BEING TRUSTED. PMID- 26665733 TI - CHA RELEASES REVISED COMMUNITY BENEFIT RESOURCES. PMID- 26665734 TI - Celebrating Human Dignity: Two Documents of Vatican II. PMID- 26665735 TI - [ADULT STEM CELLS AND CELLS OF MALIGNANT ORIGIN. PART I]. AB - Recent data on adult stem cells are reviewed. According to the present dominant paradigm, it is most probable that cancer predisposition arises or cancer is initiated in these cells. PMID- 26665736 TI - [CONJUGATIVE INTEGRATIVE ELEMENTS (ICEs) OF MICROORGANISMS]. AB - Integrative conjugative elements (ICEs) are an extensive group of mobile genetic elements found in the Gram-positive and Gram-negative bacteria. These genetic elements are replicated being incorporated into host chromosome, but retain the ability for excision and conjugative transfer. Given a set of the genes of the conjugative transfer, control of removal and integration, ICEs are directly involved in the processes of horizontal transfer of genetic determinants, which increase the adaptive potential of the bacterial species, as well as act as a mobilizing factor for other genetic elements. PMID- 26665737 TI - [BIOFILM FORMATION BY STREPTOCOCCUS PNEUMONIAE]. AB - The biofilm process in Streptococcus pneumoniae (pneumococcus) is described. Virtually all wild-type pneumococci are capable of the biofilm formation. The pneumococcal capsule may reduce the biofilm production, and the propensity to form biofilms has a reverse correlation with the amount of the capsule material. Invasive pneumococcal isolates and noninvasive strains that persist in the nasopharynx have different biofilm potential. A number of issues related to effector and regulatory factors in the pneumococcal biofilms are discussed in this review. In the summary, a biofilm may be essential only for the persistent pneumococcal infection. PMID- 26665738 TI - [MOLECULAR MECHANISMS OF DRUG RESISTANCE NEISSERIA GONORRHOEAE HISTORY AND PROSPECTS]. AB - Neisseria gonorrhoeae (gonococcus) is a strict human pathogen, which causes gonorrhea--an infectious disease, whose origin dates back to more than two thousand years. Due to the unique plasticity of the genetic material, these bacteria have acquired the capacity to adapt to the host immune system, cause repeated infections, as well as withstand antimicrobials. Since the introduction of antibiotics in 1930s, gonococcus has displayed its propensity to develop resistance to all clinically useful antibiotics. It is important to note that the known resistance determinants of N. gonorrhoeae were acquired through horizontal gene transfer, recombination and spontaneous mutagenesis, and may be located both in the chromosome and on the plasmid. After introduction of a new antimicrobial drug, gonococcus becomes resistant within two decades and replaces sensitive bacterial population. Currently Ceftriaxone is the last remaining antibiotic for first-line treatment of gonorrhea. However, the first gonococcus displaying high level resistance to Ceftriaxone was isolated in Japan a few years ago. Therefore, in the near future, gonorrhea may become untreatable. In the present review, we discuss the chronology of the anti-gonorrhea drugs (antibiotics) replacement, the evolution of resistance mechanisms emergence and future perspectives of N. gonorrhoeae treatment. PMID- 26665739 TI - [APPLICATION OF PULSED FIELD GEL ELECTROPHORESIS FOR MOLECULAR TYPING OF CAUSATIVE AGENTS OF ESPECIALLY DANGEROUS INFECTIONS]. AB - The macro-restriction analysis of the microorganism DNA with the use of gel electrophoresis in pulsed field (PFGE typing, pulse electrophoresis) is applied in molecular biology to study the clonal structure and typing of causative agents of infectious diseases. Determining the degree of the relationship and definition of epidemiological interrelations of studied isolates, as well as studying the evolutionary history of pathogens, is performed by comparing DNA restriction patterns. This review presents an analysis of the use of the pulse electrophoresis in molecular-epidemiological research and the study of phylogeny of especially dangerous infections, cholera, and plague. The possibility of genetic heterogeneity of the Vibrio cholerae and Yersinia pestis populations is demonstrated; territorial and epidemiological characteristics of the spread of different isolate pulso-types, problems and prospects of the PFGE typing method in the system of epidemiological surveillance of cholera and plague in Russia are discussed. PMID- 26665740 TI - [CONSTRUCTION AND PROPERTIES OF THE FRANCISELLA TULARENSIS VACCINE STRAIN WITHOUT ONE COPY OF THE IGLC GENE AND WITHOUT RECA GENE]. AB - The live vaccine based on the Francisella tularensis subsp. holarctica vaccine strain 15 NIIEG line is used in Russia against tularemia. This vaccine is highly effective, but fairly unstable. Therefore, development of stable live tularemia vaccine with minimal side effect is rather urgent. The method of allel removal in the F. tularensis vaccine strain was used to remove one copy of the iglC gene, which is required to provide intracellular production of the vaccine strain, as well as removal of the recA gene. The latter is crucial for homological recombination. pGM5 suicide vector based on pHV33 bireplicon plasmid was constructed to provide replacement of intact F. tularensis chromosome segments by modified segments. Modified chromosome segments contain F. Tularensis DNA fragment without iglC structural gene segment 545 p. b. (in pGMDeltaiglC plasmid), as well as DNA fragment containing no recA structural gene segment 1060 p.b. (pGMDeltarecA plasmid). The constructed 15/23-1DeltarecA mutant, in contrast to the vaccine strain 15, was capable of reproducing in the macrophage-like cells J774A.1 line, whereas the efficiency of the reproduction was 8-10 times less. BALB/c mouse responded to immunization by the 15/23-1DeltarecA strain by smaller weight decrease (-2%) as compared to the strain 15 (-14%). Bacteria of the 15/23 1DeltarecA strain were virtually incapable of germinating from the BALB/c murine spleen 14 days after invasion, whereas bacteria of the strain 15 were found in the murine organs even after 21 days. The F. tularensis 15/23-1DeltarecA strain having smaller reaction ability can be used as a basis for construction of stable live safe tularemia vaccine. PMID- 26665741 TI - [VIth International School of Molecular Genetics for Young Scientists: Genomics and System Biology]. PMID- 26665742 TI - [A winning award for the excelling research papers for 2015 on behalf of the Israel Medical Association]. PMID- 26665743 TI - [WHO AFFECTS THE PATIENT, DR. GOOGLE OR THE DOCTOR?]. AB - In the last decade the World Wide Web has become one of the prime sources for medical data searches. The abundance of information and emphasis on consumer communication, which are the main characteristics of the new generation of the web named "Web 2.0", enable users to engage and educate others by sharing and collaborating knowledge. It also enables them to receive medical information based on the experience of other patients, while the duration of the traditional physician's visit has shortened. However, using Web 2.0 for health collaboration has drawbacks as well: When alternative ways of "knowing" replace objective medical facts, there is danger of misinformation and truth "flattening". This article examines the distribution of medical misinformation online: Its characteristics, the nature of the messages presented online and the means that might help protect users and patients from it. The authors hold positions in the Israeli Dairy Board (IDB): Dr. Averch manages the health field on the IDB, and the findings in this article are based on research that she is leading as part of this position, and Dr. Mishali is a trained psychologist, and acts as a strategic consultant for IDB in the field of coping with the opposition to milk and its products. In this article it is initially shown how the characteristics of information distribution in general help spreading medical misinformation online: The decline of doctors' authority as sole providers of medical information, disillusionment and suspicion towards science and the notion of expertise, and the emergence of new ways to evaluate information, based on community ties. The nature of this pseudo-medical information will then be discussed, including the range of the phenomenon and the probability of users to be affected by it. Furthermore, we will raise specific tactics in which anti-establishment messages are portrayed; examples will be given of the use of emotion evoking content in the anti-establishment messages in order to arouse comment. It will be demonstrated in anti-dairy products and anti-vaccination campaigns. The impact of pseudo-medical language on consumers will be debated, although the content can easily be scientifically disproved. Finally, recommendations for a better medical dialogue with the patient, based on the online arena of medical knowledge described, will be provided. PMID- 26665744 TI - [ONE YEAR FOLLOW-UP OF PATIENTS AFTER CARDIAC ARREST TREATED WITH THERAPEUTIC HYPOTHERMIA: PROSPECTIVE COHORT STUDY COMPARED WITH HISTORICAL CONTROL]. AB - BACKGROUND: Mild therapeutic hypothermia has been shown to reduce mortality and neurological morbidity in post cardiac arrest survivors. These beneficial effects had initially been reported in retrospective studies and subsequently more evidence has been gathered by two cornerstone randomized control trials. All these studies focused on the acute outcome and the clinical status at the time of hospital discharge. The main goal of this study was to describe the long term effects of therapeutic hypothermia in this population. PATIENTS AND METHODS: A prospective cohort with a historical control group was used in this study. All consecutive patients eligible for therapeutic hypothermia after cardiac arrest were enrolled. These patients were compared to an historical control group of patients who had met the same criteria of treatment with therapeutic hypothermia, but were not treated since it was not yet available. Patients' records and clinical assessment at 1 week, one, six and twelve months follow-up were collected. RESULTS: In the present study 54 consecutive patients were recruited prospectively, treated with mild hypothermia and 41 patients served as the historical control group for a similar period of time. The cooling group was significantly younger than the control group, 54 +/- 16.3 versus 61.1 +/- 14.5 years (p < 0.04). Peripheral arterial embolism complication was more common in the hypothermia group. 11.1% versus 0% (p < 0.035). No other clinically meaningful differences were found. In this respect, the beneficial trend towards reduced neurological outcome and mortality was observed in favor of the cooling group, which was statistically significant at six months follow-up (p < 0.044). Beyond 6 months the differences did not reach statistical significance. CONCLUSION: In the current phase of the study, a tendency in favor of mild cooling was observed in the short and medium term outcomes in patients resuscitated after out of hospital cardiac arrest due to fatal arrhythmia. The current results indicate that in spite of high survival rates after the acute stage in the cooling group, the long term mortality rate in this group is still high. PMID- 26665745 TI - [TEN YEARS OF OPIOID CONSUMPTION BY CHILDREN (2001-2010)]. AB - BACKGROUND: Opioids are considered a cornerstone in the treatment of pain. They are rarely used in almost half of the countries of the world, especially in children. OBJECTIVE: The aim of this study was to assess opioid use over a ten year study period from 2001-2010, among children 0-18 years old who are members of Clalit Health Services (CHS), the largest HMO in Israel METHODS: Data on the purchase of opioids, authorized for use in Israel, was obtained from the computerized databases of CHS. In addition, the patient's demographic details and cancer morbidity were also extracted. The data was analyzed after all the doses of all opioids consumed (fentanyl patch, oxycodone, methadone, hydromorphone, oral transmucosal fentanyl) were converted into oral morphine equivalents (OME). RESULTS: In all, 1,098 children purchased at least one opioid prescription during the study period. Of them, 27.3% had a diagnosis of cancer and 55.5% were female. A 42% decrease in total annual OME (mg) purchased, from 209,443 mg to 122,048 mg, was observed from 2001 to 2010. There was no specific pattern or trend in the annual number of pediatric and adolescent patients who purchased at least one opioid drug during the study period. In 86.5% of the cases, children with a non cancer cause of pain purchased opioids for only one month. CONCLUSIONS: There is a low and inconsistent rate of opioid consumption among pediatric and adolescent members of the CHS. Further study is needed to explore the reasons for this low opioid consumption rate in this population group. PMID- 26665746 TI - [THE ADDED VALUE OF ART THERAPY FOR MOTHERS WITH POST-PARTUM DEPRESSION IN ARABIC SOCIETY IN ISRAEL]. AB - INTRODUCTION: Post-partum depression (PPD) is a neurotic condition, which appears usually within two months after the delivery. This is the most common complication of pregnancy and puerperium, affecting about 15 to 20% of the mothers. In Israel, with some 150,000 deliveries annually, this relates to about 20,000 women each year. Routine treatment with psychotherapy (PT), helps about two thirds of these women. Continuation of the maternal symptoms affects the baby's development, and the rest of the family as well. OBJECTIVES: The purpose of this study was to evaluate the additional value of art therapy (AT), compared to standard therapy, with PT alone, to eradicate symptoms of depression. METHODS: A prospective, randomized controlled study was conducted. During the period 2011 2013, a total of 141 Arab mothers with symptoms of PPD, from the Um-El-Fahem region, were included in the study. A comparison was made between two groups: The control group receiving routine treatment with PT and the intervention group which received, in addition, AT. RESULTS: Both groups demonstrated a reduction in the level of depressive symptoms. In the intervention group, however, the reduction in the level of depressive symptoms was statistically more significant (p < 0.05). CONCLUSIONS: In our study, the combination of standard PT with AT enabled the vast majority of the mothers to recover from the depressive state. In a health care system with chronic budgetary constraints, the addition of some cardboard and plasticine to the "Health Basket", coupled with a few hours with a trained therapist, is probably a worthy alternative, considering the scope of the problem and its influence on the mother, the baby, and the family as a whole. SUMMARY: The appearance of PPD symptoms is a common and significant medical condition. These attributes make this phenomenon a significant problem from the public health perspective. Routine treatment with PT, helps a lot of women. Many, however, remain symptomatic. The addition of AT enables most of them to resume a normal and healthy course of life. PMID- 26665747 TI - [KIDNEY TRANSPLANTION IN A MENTAL HEALTH PATIENT]. AB - This journal has previously published articles on the issue of kidney transplantation in mentally ill patients. The current case report highlights the issue of kidney transplantation in a patient suffering from a psychotic disorder. The case study describes a patient who, although he does not comply with his psychopharmacological treatment, fully complies with all medications pertaining to his physical illness. The conclusion from this case study is that mentally ill patients are not a homogenous group and we need to discuss each case independently, with regard to the complexities of each patient. PMID- 26665748 TI - [GLAUCOMA AND METABOLIC RISK FACTOR SCREENING OF ATTENDEES DURING THE 41ST ISRAEL MEDICAL ASSOCIATION CONVENTION]. AB - BACKGROUND: Despite the immediacy of medical resources, screening practices seem inadequate among health professionals. OBJECTIVES: The main purpose of this study was to increase awareness among decision makers in the medical community to population screening of metabolic risk factors and glaucoma. Evaluation of their self-practice regarding such screening was subsequently performed. METHODS: Attendees of the 41st Israel Medical Association's Convention were screened voluntarily for glaucoma and metabolic risk factors. Participants underwent intraocular pressure measurement, evaluation of anterior chamber depth and cup/disc ratio of the optic disc, measurement of blood pressure, weight, height, hemoglobin A1C and total cholesterol. RESULTS: An eye examination was performed in 118 individuals with a mean age of 52 +/- 10.8 years. A positive family history for glaucoma was reported in 14.4%. Twenty six percent of the participants had never been examined by an ophthalmologist. One individual had elevated intraocular pressure. An enlarged cup-disc ratio was detected in 8 participants (6.8%). Hypercholesterolemia was found in 22%, hypertension in 45%, elevated hemoglobin Al C levels in 9% and a body mass index > 25 in 73%. CONCLUSIONS: A substantial number of health-care providers had inadequate own screening practices and abnormal findings in screening tests for glaucoma and metabolic risk factors. This suggests that more efforts should be invested to stimulate and optimize screening practices among members of the medical community. PMID- 26665749 TI - [THE ROLE OF PET/CT IMAGING IN THE ASSESSMENT OF INFECTION]. AB - Diagnosis (essentially early detection of infection) and also management decision making pose clinical challenges. Many resources are invested in developing precise, non- invasive diagnostic tests and efficient therapies for infectious processes. Nuclear medicine procedures are part of the evaluation armamentarium of patients with suspected or confirmed infection. Their strength relies on the fact that they are non-invasive tests that provide both functional as well as metabolic information early during the course of disease. The most frequent nuclear medicine procedures used in the assessment of infection are bone, Gallium and labeled white blood cells scans. PET/CT, using mainly labeled glucose (FDG), is redefining the diagnostic work-up and is currently leading to changes in the management of patients with suspected or known infections. Current evidence supports the use of FDG imaging as a first-line diagnostic tool in patients with suspected or known infectious processes, with convincing data available mainly for indications such as fever of unknown origin (FUO), vertebral osteomyelitis, vasculitis and vascular graft infection. Whether FDG-PET/CT or hybrid imaging with new, more infectious-specific tracers will replace standard nuclear medicine procedures or stand-alone conventional imaging modalities, is still debatable. The future looks promising and the role of molecular hybrid imaging techniques in the assessment of inflammatory and infectious processes is undoubtedly on the rise. PMID- 26665750 TI - [QUALITY MEASURES IN MEDICINE-- A PLEA FOR NEW, VALUE BASED THINKING]. AB - Quality is an important and basic conduct of complex systems in general and health systems in particular. Quality is a cornerstone of medicine, necessary in the eyes of the community of consumers, caregivers, and the systems that manage both. In Israel, the Ministry of Health has set the quality issue on the agenda of healthcare organizations in all existing frameworks. In this article we seek to offer an acceptable alternative perspective, in examining the quality of public health. We suggest highlighting the ethical aspect of medical care, while reducing the quantitative monitoring component of existing quality metrics. Relying solely on indices has negative effects that might cause damage. The proposed alternative focuses on the personal responsibility of health care providers, using. values and moral reasonin. PMID- 26665751 TI - [Thundering exhaustion: professional burnout among physicians in Israel]. PMID- 26665752 TI - [TURNOVER CAPSULAR FLAPS FOR THE TREATMENT OF IMPENDING EXTRUSION OF SILICONE PROSTHESIS IN RECONSTRUCTED BREASTS]. AB - Pressure necrosis which might be followed by skin necrosis and implant extrusion is a dreaded complication of breast reconstructive surgery. Over the years, several techniques have been introduced to address this challenging problem. We offer a novel surgical technique to confront this perplexing complication. By using the capsule of the implant as a turnover flap, the soft tissue coverage is enhanced thereby decreasing the pressure between the breast prosthesis and the over-laying skin. The technique is simply reproduced, requires no new incisions, and avoids further morbidity to the involved breast reconstructed patient. PMID- 26665753 TI - [INTRAVENOUS CHEMOTHERAPY VERSUS INTRAPERITONEAL CHEMOTHERAPY IN ADVANCED OVARIAN CANCER: UPDATE ON THE SITUATION WORLDWIDE AND IN ISRAEL]. AB - Ovarian cancer is the second in incidence and the first cause of death. As much as 70% of ovarian cancer patients are diagnosed with advanced disease. The standard treatment of advanced ovarian cancer is a combination of primary optimal debulking (POD) followed by a combined adjuvant chemotherapy treatment. Another optional treatment includes neoadjuvant chemotherapy followed by optimal debulking and then adjuvant chemotherapy. The common adjuvant chemotherapy includes a combination of platinum and taxol compounds given intravenously. Other possible treatments which had been evaluated in the past decades include a combination of chemotherapy given intravenously and intraperitoneally. The rationale behind delivering the chemotherapy intraperitoneally is to provide a much higher concentrations of cytotoxic agents in the peritoneal cavity and to reduce the systemic side effects. A number of randomized trials have shown that the combination of IV and IP chemotherapy entails a survival advantage. Most studies included treatment based on cisplatin treatments with/ without taxol given intravenously versus a combined treatment (intravenously and intraperitoneally) of those agents. An advantage of up to 8 months in disease free survival and 11 months in overall survival was noted in the IP group. On the other hand, this treatment led to a higher rate of side effects, including abdominal pain, electrolyte imbalance and catheter related complications. Despite the inconsistency in the treatment protocols between the different trials comparing intravenous and intra-peritoneal treatment, one cannot ignore the statistical significance between the groups, for disease-free survival and overall survival. That is why, when addressing patients who completed optimal surgery, one needs to conduct a thorough evaluation regarding the complementary chemotherapy treatment. Due to the broad side effect profile, special notice should be taken as to the patient's age, medical history, and performance status after the primary surgery and her ability to endure an aggressive chemotherapy treatment. By doing so, it will be possible to select the ovarian cancer patients who will benefit he most from combining intravenous and intraperitoneal treatment. PMID- 26665754 TI - [ETHICS, MORALS AND SOCIETY IN PERSONALIZED MEDICINE]. AB - Following the completion of the human genome project, genomic medicine including personalized medicine, widely based on pharmacogenetics and pharmacogenomics, is rapidly developing. This breakthrough should benefit humankind thanks to tailoring the most appropriate prevention, interventions and therapies to each individual, minimizing adverse side effects, based on inter-personal genetic variety and polymorphism. Yet wide spectrum ethical, legal and social issues carry significant implications regarding individuals, families, society and public health. The main issues concern genomic information and autonomy, justice and equity, resources allocation and solidarity, challenging the traditional role of medicine and dealing with unlimited boundaries of knowledge. Those issues are not new nor exceptional to genomic medicine, yet their wide unlimited scope and implications on many aspects of life renders them crucial. These aspects will be discussed in light of Beauchamp and Childress' four principles: non-maleficence, beneficence, autonomy and justice, and main moral philosophies, Kant's autonomy, Utilitarianism which promotes the common good, and Rawls' Theory of Justice. PMID- 26665755 TI - [Male versus female nouns in the Hebrew language]. PMID- 26665756 TI - [GENETIC RISK FACTORS FOR MULTIPLE KIDNEY STONE FORMATION IN THE RUSSIAN POPULATION]. AB - This study examines the association of multiple kidney stones with polymorphisms of urolithiasis candidate genes in the Russian population. A total of 75 adult patients with multiple stones (the main group) residing in the Central Russia and 189 healthy adults (control group) from the same region underwent genetic testing. The study group consisted of 41 (54.7%) males and 34 (45.3%) females with mean age 44.5 +/- 14 years. The material for the study was samples of venous blood. Spectrum and frequency of polymorphic variants of four urolithiasis candidate genes were determined using real time PCR: the Klotho gene (KL, rs526906), vitamin D receptor gene (VDR, rs1540339), gene of the extracellular calcium-sensitive receptor (CASR, rs2202127), calcium release-activated calcium modulator 1 (ORAI1, rs7135617). Fisher angular conversion and chi2 tests showed association between the genetic polymorphisms of ORAI1 and multiple kidney stone formation in the Russian population. No association was found between multiple kidney stones and polymorphisms of genes encoding KL, VDR, CASR. These results indicate that genetic factors, in particular polymorphic variants of the ORAI calcium release-activated calcium modulator 1 (ORAI1, rs7135617), may affect multiple kidney stone formation in the Russian population. PMID- 26665757 TI - [THE ROLE OF 3D-COMPUTER SIMULATION IN IMPROVING THE STAGHORN NEPHROLITHIASIS TREATMENT RESULTS]. AB - This article presents the experience of applying 3D-computer simulation for treatment planning in patients with coral kidney stones. The impact of the kidney internal structure and the nephrolithiasis stage on the treatment results of the patients with staghorn stones are analyzed on the basis of authors' own experience. They note the usefulness of computer modeling in preoperative planning for improving the treatment results and preventing intraoperative complications. PMID- 26665758 TI - [RATIONAL THERAPY FOR RECURRENT INFECTIONS OF THE LOWER URINARY TRACT. THE RESULTS OF A PROSPECTIVE OBSERVATIONAL PROGRAM TO ASSESS THE EFFECTIVENESS AND SAFETY OF CEFORAL(r), SOLUTAB(r)* AND URO-VAKSOM(r) IN PATIENTS WITH RECURRENT UNCOMPLICATED LOWER URINARY TRACT INFECTIONS (FLORA)]. AB - Remaining generally unchanged, urinary tract infection (UTI) treatment protocols require continuing monitoring due to growing antibiotic resistance and lowered immune status of the majority of patients. The article presents the results of a prospective observational program carried out the Russian Federation in to assess the effectiveness and safety of Ceforal(r), Solutab(r) and Uro-Vaksom(r) in patients with recurrent uncomplicated lower urinary tract infections (FLORA). The results of the program suggest that Ceforal(r) Solutab(r) and Uro-Vaksom(r) administered as a part of routine clinical practice contribute to a significant reduction in the number of UTI recurrences and have a good safety profile. These findings support recommendation to use this treatment protocol in patients with recurrent UTI, taking into account individual and epidemiological features. PMID- 26665759 TI - [CHRONOBIOLOGICAL ASPECTS OF THE USE OF PROLIT SUPER SEPTO IN PATIENTS WITH INFECTIOUS AND INFLAMMATORY DISEASES OF THE URINARY SYSTEM]. AB - This paper presents results of a study involving 120 patients with infectious and inflammatory diseases of the urinary system, divided into four groups. Groups 1 and 3 included patients with acute serous non-obstructive pyelonephritis, groups 2 and 4--patients with exacerbation of chronic recurrent bacterial cystitis. Patients in groups 3 and 4 received a 10 day course of antibiotic therapy combined with Prolit super septo while patients in groups 1 and 2--only the standard antibiotic therapy. The authors studied changes in the clinical presentation, chronorhythms and psycho-emotional condition of the patients. At baseline, all patients showed signs of severe desynchronosis and psycho-emotional disorders. Combination therapy with Prolit super septo more effectively suppressed inflammation, improved clinical symptoms, corrected patient psycho emotional status and restored normal chronorhythms regardless of the inflammation location. PMID- 26665760 TI - [EXPERIMENTAL MODELS OF STRESS URINARY INCONTINENCE]. AB - Despite numerous medical and surgical treatment strategies available, the problem of stress urinary incontinence (SUI) in women is still not completely resolved. Continuing research is underway to modify the sling operations and develop new bulk-enhancing agents, including the use of tissue engineering and cell technologies. To evaluate the safety and effectiveness of new methods at the preclinical stage, adequate and reproducible experimental models of SUI in laboratory animals should be used. This article presents analysis of all SUI models described in the scientific literature and the results of an experimental study comparing two primary ways of modeling, based on bilateral pudendal nerve damage in female rats. The experiment results showed that only bilateral electrocoagulation of proximal part of pudendal nerves by the posterior approach ensured a stable and long-term SUI symptoms in animals in the form of leak point pressure reduction in the urodynamic study and increase of the of the urethral lumen according to histomorphometric analysis. The results suggest that an adequate experimental SUI model is urethral rabdomiosphincter denervation by pudendal nerve electrocoagulation by the posterior surgical approach, when the nerve is damaged in the area of its separation from sciatic nerve. In this case stable and reproducible results are obtainable. PMID- 26665761 TI - [VIRAL INFECTIONS: HUMAN PAPILLOMAVIRUS AND GENITAL HERPES TYPE 1 AND TYPE 2 AS A CAUSE OF CHRONIC RECURRENT CYSTITIS WITH SEVERE DYSURIA IN WOMEN WITH URETHRAL HYPERMOBILITY AND HYPOSPADIAS]. AB - Female hypospadias presenting as a misplaced urethral opening is a common cause of chronic recurrent cystitis. Cystitis occurs when urogenital infection and anaerobic bacteria enter the urethra and bladder from the vagina. The authors argue that chronic infections of the lower urinary tract in women with hypospadias should be treated surgically by meatal transposition. They present a study confirming the role of the antiviral drug Panavir in prevention of inflammatory complications in the postoperative period in patients with a history of viral infection (human papillomavirus and herpes). PMID- 26665762 TI - [TITANIUM NICKELIDE TECHNOLOGIES IN MINIMALLY INVASIVE SURGERY OF KIDNEY AND UPPER URINARY TRACT]. AB - The most common pathology of the kidney and upper urinary tract includes nephrolithiasis, ureteral strictures and renal cysts. In the treatment of patients with these diseases, the majority of surgeons prefer minimally invasive techniques, including endoscopic surgery. The complication rate of percutaneous surgery is a major factor in encouraging the search for new treatments. We have analyzed the results of 402 x-ray-endoscopic operations performed with the use of technologies based on titanium nickelide materials in patients with nephrolithiasis, ureteral strictures and kidney cysts. The high effectiveness and reliability of porous titanium nickelide cryoapplicator was noted in control of percutaneous channel bleeding and prevention. The proposed suspension nephropexy with fine titanium granules in coexisting nephrolithiasis and nephroptosis demonstrated 1.5 times greater effectiveness compared to the traditional nephropexy, reducing duration of nephrostomy and rehabilitation by almost 3 times. The proposed methods of intubation by permanent and temporary stents with shape memory after percutaneous ureteropelvic junction stricture correction are promising in the treatment of patients with this pathology of the upper urinary tract. Application of titanium nickelide implants in simple renal cyst surgery has led to a significant increase in the effectiveness of these operations, improvement in long-term results and patients' quality of life. PMID- 26665763 TI - [CLASSICAL RADICAL EXTRAURETHRAL METHOD OF ADENOMECTOMY--BEYOND 30 YEARS]. AB - Introduction of transvesical extraurethral adenomectomy into clinical practice was preceded by the clinical and morphological study of the prostate, prostatic urethra, bladder, upper urinary tract and renal function. It was found that at any volume of adenomatous (hyperplastic) tissue in the prostate, front semicircle around the prostatic urethra remains intact, and changes occur only in the proximal part of its back semicircle. Front semicircle adherent to the anterior commissure of the prostate has no adenomatous tissue. Extraurethral method enables you to perform a prostatectomy at any size of adenomatous tissue (fragmentarily) with preservation of the prostatic urethra, urethral vascular plexus and, if necessary, to carry out the vesico-urethral segment correction without blood loss. Free independent urination is recovered at days 10-12 after the healing of the suprapubic surgical wound and removal of drainage tube. Since the introduction of transvesical extraurethral prostatectomy into clinical practice, more than 3,000 radical adenomectomies at different stages in patients with co-morbidities were performed only at Burdenko Central Military Clinical Hospital and the 2nd Mandryka CMCH. PMID- 26665764 TI - [COMPARATIVE ANALYSIS OF POSITIVE SURGICAL MARGIN RATES IN PATIENTS UNDERGOING ROBOT- ASSISTED OR RETROPUBIC RADICAL PROSTATECTOMY FOR PROSTATE CANCER]. AB - The issue of comparative evaluation of oncological and functional outcomes of robot-assisted radical prostatectomy (RARP) and radical retropubic prostatectomy (RRP) is widely discussed in the international literature. A key point in studying the oncological efficacy of both techniques is a comparative evaluation of positive surgical margin (PSM) rates as one of the main prognostic factors influencing the further course of prostate cancer. Available data so far are inconsistent, which prompted us to conduct our own research. A retrospective analysis was performed in two groups of patients who underwent RARP (n = 63) and RRP (n = 116) from January 2014 to April 2015. Despite a general trend towards lower PSM rates in RARP group compared to RRP group (12.7 and 21.6%, respectively, p = 0.09), no significant differences were found in the stratification of patients in both groups depending on the risk of prostate cancer progression and pathological stage. These data show the potential equality of the two methods regarding intraoperative control of resection margins. PMID- 26665765 TI - [10 YEARS' EXPERIENCE IN USING DIRECT URETEROINTESTINAL ANASTOMOSIS IN URINARY INTESTINAL DIVERSION AFTER RADICAL AND SIMPLE CYSTECTOMY]. AB - 147 patients who underwent urinary intestinal diversion from 2004 to 2014 were selected for the retrospective study. The authors carried out a comparative analysis of rates of complications that arise from the direct ureterointestinal anastomosis. The mean age of patients was 54.2 +/- 3.0 (36-69) years. 60 (40.81%) patients of group 1 underwent Nesbit's direct ureterointestinal anastomosis, while in 87 (59.19%) patients of group 2 Wallace-1 and Wallace-2 anastomoses were performed. Average follow-up was 5.6 (2-10) years. Strictures of ureterointestinal anastomosis were detected in 2 (3.38%) patients of group 1 and in 1 (1.14%) patient of group 2. In all cases re-anastomosis was performed. The maximum postoperative concentration of serum creatinine in both groups was 231 mmol/l. According to radioisotope kidney scan, no differences in accumulative and excretory renal functions between two groups of patients were recorded. No kidney stone formation in both groups of patients during the follow-up period was observed. No ureteral reflux above grade 3 was noted. The clinical manifestation of reflux pyelonephritis was observed in 3.5% of the patients. Acute pyelonephritis was cured by antibacterial therapy. PMID- 26665766 TI - [NON-NEOPLASTIC KIDNEY PATHOLOGY IN SPECIMENS AFTER TUMOR-RELATED NEPHRECTOMY]. AB - The aim of the study was to determine the incidence of pathological changes in the unaffected parts of tumor-related nephrectomy specimens. Tissue samples obtained from 507 patients were analyzed. Non-neoplastic pathology in the tumor free kidney tissue along with the tumor was detected in 63 (12.42%) cases. All non-tumor diseases co-existing with tumors were found in patients of older age groups. Approximately 1/3 of the non-neoplastic pathology was nephrosclerosis lesions (30.16%), and in half of those cases (52.63%) transitional cell carcinoma was detected. It is pointed out that for the detection of glomerular lesions careful microscopic examination of the unaffected parts of renal parenchyma is needed. The examination, carried out by means of special staining techniques (histochemistry, immunohistochemistry, immunofluorescence), electron microscopy, and with the involvement ofnephropathologists, can improve glomerular pathology detection rate after nephrectomy. PMID- 26665767 TI - [NEW OPTIONS OF ENDOSCOPIC TREATMENT FOR KIDNEY AND URETER STONES IN OBESE PATIENTS]. AB - Effective urolithiasis treatment, especially in overweight patients has a considerable medical and social implication. Extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotripsy (PCNL) in prone position of the patient are standard treatment options for kidney and ureter stones. These interventions are not always effective in patients with concomitant obesity and are associated with technical difficulties and an increased risk of complications. The study included 175 patients with obesity. The first group consisted of 96 (54.8%) patients treated with transurethral contact lithotripsy. The 2nd group consisted of 54 (30.9%) patients who underwent PCNL in the supine position. The third group comprised 25 (14.3%) patients with multiple stones of kidney and ureter, who underwent combined transurethral and percutaneous intervention in the supine position. The 1st and 3rd group had a higher prevalence of patients with II degree of obesity, in the 2nd group--with I degree of obesity. The mean duration of surgery in 1st group was 43.4 min, in the 2nd- 70.3 min and in the third--84.6 min. Method of kidney drainage depended mainly on the presence, location and size of residual stone fragments. The average duration of the kidney drainage stent in patients of the 1st group was 39 days (ureteral catheter--1.3 days). In all patients of the 2nd and 3rd groups, at the final stage of the operation a nephrostomy tube was placed for an average of 2.7 days. The average postoperative hospital stay was 2.9 days in the 1st group, 4.1 days in the 2nd group and 4.5 days in the third group. In the 1st group, the stone free status was achieved in 81 (84.4%) patients. Another 10 (10.4%) patients later needed ESWL for the complete disposal of the stones. In the 2nd group, the complete clearance of kidney stones was achieved in 49 (90.7%) patients. Another 3 (5.6%) patients required added ESWL to achieve the stone-free status. In the third group of patients stone free status was reached in 22 (88%) cases. In the remaining patients residual stone fragments were not clinically important. The most prevalent postoperative complication in all groups was postoperative pyelonephritis. Taking into account high efficiency of transurethral lithotripsy and PCNL in the supine position, as well as their combinations we can recommend these interventions to treat patients with kidney and ureteral stones and concomitant obesity. PMID- 26665768 TI - [PATHOGENETIC TREATMENT OF CHRONIC NONBACTERIAL PROSTATITIS COMPLICATED BY SPERM DISORDERS]. AB - This study examines the efficacy and safety of the natural complex of multi component biologically active dietary supplement Prostatinol in the pathogenetic treatment of 45 patients with chronic nonbacterial Prostatitis complicated by sperm disorders. Within 4 weeks 25 patients of the treatment group and 20 patients of the control group received Prostatinol or traditional anti inflammatory therapy correspondingly. The results were evaluated at weeks 4 and 12 after treatment cessation. Prostatinol was found to significantly increase the treatment effectiveness. More pronounced positive clinical effect was noted in 92% of treatment group patients receiving Prostatinol (disappearance of perineal pain, reduction of the IPSS score to an average of 2.1 points, absence of residual urine, normal Prostate echotexture, improvement of Prostate circulation, increase of sperm concentration and motility, higher pregnancy incidence among the wives of the treated patients). In the control group similar treatment effect was achieved in twice less number of patients. These results confirm that the components of the Prostatinol complex are effective, safe, have no side effects and can be used in the treatment of chronic Prostatitis, as well as for prevention of Prostatic diseases and improvement of sexual function. PMID- 26665769 TI - [APPLICATION OF INTEGRAL INDICATOR FOR ASSESSMENT OF OXIDATIVE STRESS IN MEN WITH PATHOSPERMIA AND TYPE 1 DIABETES]. AB - This study introduces a method for assessing the individual degree of oxidative stress (integral indicator) in men with pathospermia and type 1 diabetes, based on lipid peroxidation parameters. The study population consisted of three groups of patients. The study group included 15 men with type 1 diabetes (mean age 28 +/ 3.8 years) and abnormal semen analyses: oligozoospermia, asthenozoospermia and oligoasthenozoospermia. The comparison group consisted of 20 people (average age 30 +/- 2.5 years) without type 1 diabetes, but with changes in semen, similar to those in the study group. The control group was formed of 30 men (mean age 28 +/- 4.3 years) with complete reproductive function and without type 1 diabetes. The mechanisms of lipid peroxidation development were found to differ between patients with and without type 1 diabetes. In pathospermic patients without carbohydrate metabolism disorders, activation of lipid peroxidation processes was most pronounced at the stage of primary product formation--diene conjugates, while in patients with type 1 diabetes and pathospermia--at the stage of formation of ketodienes and conjugated trienes, and TBA- active products. It is recommended to take into account the integral indicator of the lipid peroxidation intensity in the development of methods for correction and prevention of reproductive disorders in men with type 1 diabetes and impaired spermatogenesis. PMID- 26665770 TI - [THE EFFECTIVENESS OF INTRACAVERNOUS AUTOLOGOUS PLATELET-RICH PLASMA IN THE TREATMENT OF ERECTILE DYSFUNCTION]. AB - This article deals with using autologous platelet-rich plasma (APRP) as a new treatment for erectile dysfunction in men. In recent years there was a significant interest in regenerative medicine technology due to its high effectiveness with a good safety and low cost. Currently APRP has been used successfully in various fields of medicine (surgery, traumatology and orthopedics, sports medicine, cosmetics). However, until now there have been no studies consistent with evidence-based medicine verifying the effectiveness and long-term results of APRP application for ED treatment. This article presents the results of a clinical study on the use of APRP in men with ED with a comparative effectiveness analysis of different ways of APRP administration and in combination with PDE5 inhibitors. Possible mechanisms of action of APRP in restoring erectile function are discussed. PMID- 26665771 TI - [FACTORS AFFECTING SPERMATOGENESIS PRESERVATION IN RATS WITH SEMINIFEROUS TRACT OBSTRUCTION]. AB - The aim of the study was to examine the effect of the seminal tract obstruction of different degree and duration on the morphological and functional condition of testicular tissue. The study was conducted in 50 male Wistar rats. Three experimental models of seminiferous tract obstruction were set up: obstruction of the proximal part of the ductus deferens, obstruction of the distal part of the ductus deferens and obstruction of at the epididymis level. Morphological evaluation of testicular tissue was performed at 3 and 6 months after the obstruction. It was found that obstruction at the epididymis level caused the most severe impairment of spermatogenesis. PMID- 26665772 TI - [EXPERIENCE WITH E. COLI LYOPHILIZED BACTERIAL LYSATE OM-89 (URO-VAKSOM(r)) IN MEN WITH ASYMPTOMATIC BACTERIOSPERMIA]. AB - Chronic prostatitis is a significant problem of modern urology because it is the most common urological disease among the male population. We consider a 3 month course of OM-89 (Uro-Vaksom(r)) the most rational treatment of asymptomatic bacteriospermia caused by not only E. coli, but also by coexisting bacteria. Administration of OM-89 (Uro-Vaksom(r)) for 3 months to patients with asymptomatic bacteriospermia resulted in greater E. coli eradication in 98% of men and no growth of microorganisms in the ejaculate in 66%. Compared to these results, after a 3-4 week course of fluoroquinolones, E. coli occurred in significant titer in 15.2%, in non-significant--in 5.7% and the absence of microbial growth was noted only in 19% of cases. The course of OM-89 (Uro- Vaksom(r)), compared with fluoroquinolones, resulted in significantly increased sperm concentration and occurrence of greater number of spontaneous pregnancies. Rate of THB (Take Home Baby) for OM-89 (Uro-Vaksom(r)) group was 21%, for fluoroquinolones treatment group--7%. PMID- 26665773 TI - [TREATMENT OPTIMIZATION IN PATIENTS WITH ERECTILE DYSFUNCTION]. AB - Erectile dysfunction (ED) is one of the most urgent problems of modern urology, significantly affecting quality of life of male population worldwide. According to European Association of Urology ED is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Premature ejaculation (PE) is also a significant medical and social issue as it seriously affects the quality of life, especially in the presence of more or less severe ED. The aim of this study was to determine the clinical efficacy and safety of combination therapy of phosphodiesterase type 5 inhibitors and dietary supplements NeyroDoz in patients with ED and PE. The study results demonstrate the effectiveness and good compatibility of phosphodiesterase type 5 inhibitors and dietary supplements NeyroDoz as a combination therapy in patients with ED and PE. Dietary supplement, having a good tolerance, reduced psychosomatic symptom and significantly increased duration of intercourse, thus significantly improving the quality of patients' sexual life. The feasibility to prolong the effect of the therapy by the individual adjustment of NeyroDoz dosing mode after a 60-day treatment course offers new opportunities for personalized medicine, and the dietary supplement may be recommended as a complementary preparation to provide an adequate sexual functioning. PMID- 26665774 TI - [TREATMENT OF ERECTILE DYSFUNCTION FOLLOWING TRANSVESICAL PROSTATECTOMY]. AB - This study examines the efficacy and safety of phosphodiesterase type 5 (PDE-5) inhibitors in treating erectile dysfunction after transvesical prostatectomy. The study involved 63 men aged 55 to 68 years, divided into two groups--29 and 34 patients, respectively. Patients in group 1 received 50 mg of sildenafil citrate (Ereksezil(r)) on a daily basis, in group 2--100 mg of sildenafil citrate (Ereksezil(r)) on demand. Postoperative visits were scheduled at the stage of screening, then after a month of treatment and on day 14 after treatment completion (3 visits altogether). Changes of patients' complaints according to IIEF-15 questionnaire showed a significant improvement in erectile function and its components of sexual life satisfaction in both groups of patients, but more significantly with regular medication intake, which has a positive impact on patients' quality of life. At the same time, treatment by PDE-5 inhibitors did not affect the maximum urinary flow rate and residual urine volume. Given the high incidence of the postoperative erectile dysfunction, postoperative administration of PDE-5 inhibitors is relevant and promising. PMID- 26665775 TI - [IS A NONBACTERIAL PROSTATITIS NONBACTERIAL?]. AB - The study involved 287 patients with chronic recurrent urethroprostatitis. In 83 (28.9%) of them the bacterial microflora in prostatic secretions was detected. The remaining 204 patients with nonbacterial prostatitis underwent in-depth laboratory testing. Cytological and immunological methods, electron microscopy, PCR, McCoy cell culture and developed by the authors the pre-culture pathogen accumulation technique were used to investigate urethral and prostatic smears. As a result C. trachomatis was detected in 84.8% of patients, T. vaginalis--75.5%, and viruses of the Herpesviridae family--in 68.6%. Co-infection was diagnosed in 82.4% of patients, no infection was found in 6.9% of patients. The highest diagnostic sensitivity and specificity were observed in the pre-culture pathogen accumulation technique. According to electron microscopy, T. vaginalis was presented in several morphological shapes: flagellated, spherical and amoeboid. Thus, in 93.1% of patients who had previously been diagnosed with nonbacterial prostatitis by standard bacterial culture, the in-depth microbiological examination identified atypical infections (chlamydia, herpes virus, trichomonas), revealing that the rate of real nonbacterial (non-infectious) prostatitis did not exceed 6.9%. PMID- 26665776 TI - [SILDENAFIL CITRATE DOSE ADJUSTMENT FOR MEN WITH ERECTILE DYSFUNCTION: PERSONALIZED APPROACH]. AB - The high prevalence of erectile dysfunction (ED) in men of all age groups with different psychogenic and organic disorders requires a personalized approach to the choice of treatment. Widely prescribed as first-line treatment for ED, sildenafil can be used in various dosages that are selected depending on comorbidities, tolerability and efficacy of the drug. Currently there is a wealth of accumulated experience of sildenafil dose adjustment depending on the severity of ED, its etiology and duration, as well as matched to the individual characteristics of copulatory activity. Divisible tablets Tornetis(r) ("Sandoz") give the opportunity to choose an effective and safe dose of sildenafil for of all patients with ED. PMID- 26665777 TI - [UROLOGY LESSONS FOR COLORECTAL SURGEONS]. AB - The anatomical and functional relationship of the pelvic organs is a prerequisite to the development of complications when performing surgical procedures in this anatomical region. Prevention and timely diagnosis of intraoperative injuries of both the urinary system organs and intestine, as well as well-coordinated work of urologist and colorectal surgeon team offer the opportunity to employ optimal tactics for the patient management. PMID- 26665778 TI - [3D-TECHNOLOGIES AS A CORE ELEMENT OF PLANNING AND IMPLEMENTATION OF VIRTUAL AND ACTUAL RENAL SURGERY]. AB - The purpose of this article is to demonstrate the role of modern computer technologies in performing virtual and actual renal tumor surgery. Currently 3D modeling makes it possible to clearly define strategy and tactics of an individual patient treatment. PMID- 26665779 TI - [MIRABEGRON--A NEW DRUG FOR TREATMENT OF OVERACTIVE BLADDER]. AB - Mirabegron is the first drug in a new class of oral therapy for overactive bladder (OAB). It is a beta-3 adrenergic agonist, a class of drugs for the first time used for the treatment of urination disorders. Recently, following many years of rigorous multicenter randomized trials mirabegron has been approved for use in Europe and North America. The clinical indication for mirabegron is overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency and other storage symptoms in both men and women. Mirabegron is used in primary patients, or in patients who previously were unsuccessfully treated with anticholinergics. The drug has a good safety profile and causes no side effects typical of anticholinergics. PMID- 26665780 TI - [REVIEW OF CLINICAL STUDIES ON COMBINATION THERAPY OF 5alpha-REDUCTASE INHIBITORS AND alpha1-BLOCKERS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA]. AB - The review presents the results of studies on combination therapy of 5alpha reductase inhibitors and alpha-blockers in patients with benign prostatic hyperplasia (BPH). These data demonstrate a significant advantage of the combination therapy versus monotherapy in terms of quality of life and subjective symptoms as well as the safety, better results in the prevention of BPH progression and acute urinary retention, and reduced need for surgery. PMID- 26665781 TI - [Aleksey Mikhailovich Voyno-Yasenetsky]. PMID- 26665782 TI - [Igor Mikhailovich Derevyanko]. PMID- 26665783 TI - Standing up for members. PMID- 26665784 TI - LONG LIVE SUPERVISION. PMID- 26665785 TI - Spending cuts and new manifestos. PMID- 26665786 TI - 'Midwives are not alone among public sector workers in terms of funding, staff levels and seven-day working issues. They are joining a movement, not an organisation'. PMID- 26665787 TI - A way of life. PMID- 26665788 TI - Rising to the better births challenge. PMID- 26665789 TI - EMOTIONAL BAGGAGE. PMID- 26665791 TI - SUPER SUPERVISORS. PMID- 26665790 TI - Out of Africa. PMID- 26665792 TI - Complementary and alternative therapies in pregnancy. PMID- 26665793 TI - Facilitate birth in water. PMID- 26665794 TI - Reflections on the Morcambe Bay investigation. PMID- 26665795 TI - Managing neonates with clavicle fractures. PMID- 26665796 TI - Carry on baby. PMID- 26665797 TI - As simple as A B C. PMID- 26665798 TI - Fighting flu. PMID- 26665799 TI - Cutting postnatal care. PMID- 26665800 TI - How life can take a turn. PMID- 26665801 TI - Granny's hands. PMID- 26665802 TI - Designs for birth. PMID- 26665803 TI - Repeat After Me. PMID- 26665804 TI - Glucose Rising. PMID- 26665805 TI - The Gum Guide. PMID- 26665806 TI - Equal Opportunity. PMID- 26665807 TI - Rustic & Refined Holiday. PMID- 26665808 TI - It's Electric. PMID- 26665809 TI - Insulin Independent. PMID- 26665810 TI - Sonic Youth. PMID- 26665811 TI - BLURRED SIGNS? PMID- 26665812 TI - Fresh From the Market. PMID- 26665813 TI - Meal Math. PMID- 26665814 TI - Hello, New CEO. PMID- 26665816 TI - THE RISE OF THE CMIO. PMID- 26665817 TI - THE NEW REALITIES OF COLLECTIONS. PMID- 26665818 TI - COST- EFFECTIVE IMAGING. PMID- 26665819 TI - ROUNDTABLE: EVOLVING IMAGE. PMID- 26665820 TI - Down to Earth Analytics. PMID- 26665821 TI - Add movement to your life. PMID- 26665822 TI - Getting Disability Benefits: Do I Need an Attorney? PMID- 26665823 TI - TYPE 2 DIABETES AND A HEALTHY FAMILY LIFESTYLE. PMID- 26665824 TI - Managing Post-holiday Stress Naturally. PMID- 26665825 TI - Traveling with Diabetes. PMID- 26665827 TI - Priming Your Feet. PMID- 26665826 TI - MEN AND LOW TESTOSTERONE. PMID- 26665828 TI - THE INS AND OUTS OF INTERNATIONAL TRAVEL. PMID- 26665829 TI - STAYING WELL ON WHEELS. PMID- 26665830 TI - Diabetes and Your Mouth. PMID- 26665831 TI - Pediatrics, Pens, and Pumps. PMID- 26665832 TI - ALL IN A DAY'S WORK. PMID- 26665833 TI - CHILDREN AND TYPE 2 DIABETES. PMID- 26665834 TI - The Shape of Things to Come. PMID- 26665836 TI - Editorial. PMID- 26665835 TI - Getting to Know You: Gabrielle Kaplan-Mayer. PMID- 26665837 TI - Respiratory rate: overlooked but vital. PMID- 26665838 TI - Productivity Comission draft report. PMID- 26665839 TI - Benefits of conferences. PMID- 26665840 TI - 'Moral panics' and asylum seekers. PMID- 26665841 TI - No place like home. Nurses and midwives tackling homelessness. PMID- 26665842 TI - Psychotropic medication and the compliant patient. PMID- 26665843 TI - Mindfulness in practice. PMID- 26665844 TI - The barriers and enablers related to the early recognition of delirium in older palliative care patients--An integrative literature review. PMID- 26665845 TI - Is work-related stress affecting nurses and midwives? PMID- 26665846 TI - Healthy healing and wound prevention. PMID- 26665847 TI - Wound healing in obese women following caesarean section. PMID- 26665848 TI - The Australian wound registry. PMID- 26665849 TI - Perioperative nursing: preventing infection behind closed doors. PMID- 26665850 TI - Infection control: it's not just what you wear--it's how you take it off. PMID- 26665851 TI - Introducing the wellbeing in wounds network. PMID- 26665852 TI - Wound management: summarised evidence. PMID- 26665853 TI - Developing wound experts in tissue viability at Canberra Hospital. PMID- 26665854 TI - AWMA Aseptic Technique Sub-Committee. PMID- 26665855 TI - Creating 'pressure awareness" in health services. PMID- 26665856 TI - Importance of the microclimate in maintaining skin integrity. PMID- 26665858 TI - Specific job specs the answer to bullying? PMID- 26665857 TI - Infection surveillance in the home healthcare setting. PMID- 26665859 TI - A nursing voice and vision. PMID- 26665860 TI - Constant clinical experience required. PMID- 26665861 TI - Qualification frustration. PMID- 26665862 TI - Maree. PMID- 26665863 TI - Compassion, Commitment, Connection: Convention Recap. PMID- 26665864 TI - A Nurse's Guide to the Prevention of Neuropathic Ulcers in Patients with Diabetes. AB - Neuropathic ulcers present a significant issue for patients with diabetes. Neuropathic ulcers reduce mobility and increase the risk for infection and other complications. Prevention of ulceration is a primary nursing goal in the care of patients with diabetes. PMID- 26665865 TI - Outcomes Achieved Through Implementation of Interdisciplinary Plans of Care. AB - The process used to implement interdisciplinary plans of care on a pilot 32-bed stroke unit to meet Joint Commission requirements is described. Outcomes achieved as a result of the change also are reviewed. PMID- 26665866 TI - Nurses' Perceptions of Role, Team Performance, and Education Regarding Resuscitation in the Adult Medical-Surgical Patient. AB - The purpose of this study was to explore nurses' perception of their roles, team performance, and educational needs during resuscitation using an electronic survey. Findings provide direction for clinical practice, nursing education, and future research to improve resuscitation care. PMID- 26665867 TI - Retrospective Case Reviews of Adult Inpatient Falls in the Acute Care Setting. AB - Hospitalized older adults are at risk for falls. Causes of falls are complex, and prevention is multifaceted. Retrospective case reviews were performed at a Vermont hospital. Findings indicated all falls occurred while patients were attempting to void independently and were not witnessed. PMID- 26665868 TI - Spouses Needs for Professional Support: The Spouses' Perspective on Communication. AB - Spouses' experiences with their partners' hospitalization and the spouses' relationship with nurses and physicians were examined. Health professionals, should reflect more on the importance. of an ongoing dialogue with the spouses of patients, ensuring they receive correct information to become more involved in supporting patients. PMID- 26665869 TI - A Review of Antihypertensive Medications, Part II. AB - Hypertension requires careful management, including lifestyle mod- ification and drug therapy. Use of angiotensin-receptor blockers, beta blockers, and calcium channel blockers is discussed. PMID- 26665870 TI - Relation of Demographics and Reported Symptoms and Medication Use in Persons with Multiple Sclerosis. AB - A study using a cross-sectional descriptive design examined symptoms, race, sex, and use of disease-modifying therapies (DMT) in persons with relapsing remitting multiple sclerosis. Significant differences in symptoms and DMT use were found among women, men, and African Americans. PMID- 26665871 TI - Recognizing Pressure Injury in the Darkly Pigmented Skin Type. AB - This case study is an empirical report of a single subject who illus- trates the consequences of inadequate skin assessment in a darkly pigmented patient. This patient was followed for 1 year, from initial hospitalization to death. PMID- 26665872 TI - Art to Heart: The Effects of Staff- Created Art on the Postoperative Rehabilitation of Cardiovascular Surgery Patients. AB - Postoperative ambulation is important for reducing complications following surgery. The type of art patients view on the ambulation route may influence the distance patients walk. In this study, patients ambulated greater distances when staff-created art was placed on hallway walls. PMID- 26665873 TI - Working Together Toward a Common Goal: A Grounded Theory of Nurse-Physician Collaboration. AB - Working together toward a common goal is an empirically derived theory that can guide education and practice to improve patient outcomes while saving money and lives. Grounded theory was used to explore nurses' and physicians' experiences with collaboration in order to understand the process intrinsically. PMID- 26665874 TI - The New 'Code of Ethics for Nurses with Interpretative Statements' (2015): Practical Clinical Application, Part II. PMID- 26665875 TI - Focus Groups. PMID- 26665876 TI - [Fourier Transform Infrared Microspectroscopy of Rat Kidney with Regard to Fa- tal Hyperthermia]. AB - OBJECTIVE: To observe the chemical groups changing in rat kidney with regard to fatal hyperthermia by Fourier transform infrared microspectroscopy (FTIR-MSP) and to provide a new method to diagnose fatal hyperthermia. METHODS: Rats were sacrificed by hyperthermia, brainstem injury, massive hemorrhage and asphyxiation and divided into groups. The renal samples were dissected immediately after death. The data of infrared spectroscopy in glomerulus were measured by FTIR-MSP. RESULTS: The absorbances of 3290, 3070, 2850, 1540 and 1396 cm(-1) significantly increased (P < 0.05), and the ratios of Al650/A3290 and A1650/A1540 significantly decreased (P < 0.05) in group of hyperthermia. CONCLUSION: FTIR-MSP can analyze the changes of chemical groups of kidney as an auxiliary diagnosis for discriminating hyperthermia with other causes of death. PMID- 26665877 TI - [Cardiac Ultrastructure and Changes of HSP70 and HIF-1alpha Expression in Electric Shock Death Rats]. AB - OBJECTIVE: To observe cardiac ultrastructure and the expression of heat shock protein 70 (HSP70) and hypoxia inducible factor-lalpha (HIF-lalpha) in electric shock death rats and to explore the application of these indexes as the basis of medical identification in electric shock death. METHODS: Seventy-two SD rats were randomly divided into electric shock death group, postmortem electric shock group and the control group. The changes of myocardial ultrastructure were observed by transmission electron microscope, and the expressions of myocardial HSP70 and HIF 1alpha were observed by immunohistochemical technology. RESULTS: Myocardial myofibril fracture, mitochondrial cristae and membrane dissolution, and disordered arrangement of Z lines and M lines were observed in electric shock rats. HSP70 and HIF-lalpha were strong positive expressions in the electric shock death group, significantly compared with the control and postmortem electric shock groups (P < 0.05). CONCLUSION: The expressions of HSP70 and HIF-lalpha were obviously increased in electric shock death group, which may be used as the diagnostic indicator of electric shock death. PMID- 26665878 TI - [Changes of HCN4, Cx43 Expression in the Sinoatrial Node of Electric Shock Death]. AB - OBJECTIVE: To investigate the expression of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin43 (Cx43) in the sinoatrial node of electric shock death. METHODS: As experimental group, 34 cases of electric shock death who had definite current mark evidence were selected from pathology department of Xuzhou Medical College from 2010 to 2013. As the control group, 20 cases of fatal severe craniocerebral injury in traffic accidents were chosen. The expressions of HCN4 and Cx43 in the sinoatrial node were observed by immunohistochemical technology. RESULTS: HCN4 positive cells expressed in the cell membrane and cytoplasm of the sinoatrial node. Cx43 positive cells expressed in the cell membrane and cytoplasm of T cells and myocardial cells. The expression of HCN4 was significantly higher than that of the control group (P < 0.05) and the expression of Cx43 was significantly lower than that of the control group (P < 0.05). CONCLUSION: The changes of HCN4 and Cx43 expressions in the sinoatrial node illustrate electric shock death might be related to the abnormalities of cardiac electrophysiology and conduction. PMID- 26665879 TI - [Validation of GlobalFiler(r) PCR Amplification Kit and the STR Polymorphism]. AB - OBJECTIVE: To test the technical parameters of GlobalFiler(r) PCR Amplification Kit for its application to forensic application value and to investigate the genetic polymorphisms. METHODS: The validation was conducted in sensitivity, mixed samples, species specificity, adaptability, survivability, consistency, peak height balance and stability. The amplification and detection of the genomic DNA from 373 unrelated individuals from Beijing Han nationality were extracted by automation workstation. RESULTS: Global-Filer(r) PCR Amplification Kit was adaptive to some mixed, degraded and inhibited samples. The power of sensitivity and adaptability and peak height balance showed well. The distributions of genotype frequencies for 21 STR loci in the population were all in accordance with Hardy-Weinberg equilibrium (P > 0.05). The PIC value of the 21 STR loci was among 0.536 to 0.940; the H value was among 0.558 to 0.933; the DP value was among 0.783 to 0.992; the PE value was among 0.243 to 0.874. CONCLUSION: GlobalFiler(r) PCR Amplification Kit is suitable for criminal cases and DNA database in forensic practice. And 21 STR loci in Beijing Han nationality have high polymorphism, which have application value in forensic practice and population genetics. PMID- 26665880 TI - [Long Backbone Fracture Caused by Blunt Force: 99 Cases Analysis]. AB - OBJECTIVE: To investigate the main point of long backbone fracture caused by blunt force in forensic clinical identification and to provide a reference for the inspection and appraisal practices of such injury. METHODS: Ninety-nine cases of adult long backbone fractures were collected from January 2006 to December 2013 in Gutian County of Fujian Province. According to the terms of fracture location, mode of injury, type, the data were summarized. RESULTS: In the 99 cases, there were 36 cases caused by hitting, kicking, and falling and 63 cases caused by vehicle collision. The majority of the former was ulna, and those of the latter were tibia and fibula. The types of fracture were transverse one, short oblique one, long oblique one, and spiral one. CONCLUSION: Different types of long backbone fracture, not only causing stress load of fractures as well as structural differences related to each segment. PMID- 26665881 TI - [Forensic Investigation of GoldeneyeTM DNA ID 22NC Kit]. AB - OBJECTIVE: To investigate the genetic data of 21 autosomal STR included in GoldeneyeTM DNA ID 22NC Kit in Chinese Han nationality and to evaluate the forensic application. METHODS: By detected 500 unrelated healthy individuals in Chinese Han nationality of East China with GoldeneyeTM DNA ID 22NC Kit, allele frequencies, population genetics parameters and linkage disequilibrium information of the 21 autosomal STR were statistically analyzed. RESULTS: In the 21 autosomal STR, no deviations from Hardy-Weinberg equilibrium were detected and all loci were independent form each other. DP values of 21 autosomal STR were all above 0.85, and the combined discrimination power was 1-3.616 5 x 10(-26). Combined mean exclusion chance of this system in duo cases was 1-2.786 81 x10( 6), in trio cases was 1-8.545 82 x 10(-1). CONCLUSION: Twenty-one autosomal STR included in GoldeneyeTM DNA ID 22NC Kit are highly polymorphic in the Han nationality. Combined with GoldeneyeTM DNA ID 20A Kit, the kit can satisfy the needs for full-sibling testing and facilitate the solution of this kind of case tools. PMID- 26665882 TI - [Forensic Validation of the GoldeneyeTM DNA ID 25A Kit]. AB - OBJECTIVE: To test and estimate the forensic application of GoldeneyeTM DNA ID 25A Kit. METHODS: The kit was validated by a series of tests for accuracy, sensitivity, consistency, peak height balance, stability, and mixed samples through measured blood samples and other samples in routine casework. RESULTS: The peak height balance of the different loci was >= 42%. The genotyping results of the positive control DNA was accurate. The complete STR genotyping result could be obtained from 0.125 ng positive control DNA. CONCLUSION: GoldeneyeTM DNA ID 25A Kit is suitable for criminal cases and DNA database in forensic practice. PMID- 26665883 TI - [Research Advances in Postmortem Chemistry]. AB - Postmortem chemistry is becoming more and more essential in routine forensic pathology and has made considerable progress over the past years. Biochemical analyses of vitreous humor, blood, urine and cerebrospinal fluid may provide important information in determining the cause of death or in elucidating forensic issues. Postmortem chemistry may be essential for the determination of cause of death when morphological methods (diabetes mellitus, alcoholic ketoacidosis and electrolytic disorders) cannot detect the pathophysiological changes involved in the death process. It can also provide many information in other forensic situations, including myocardial ischemia, sepsis, inflammation, infection, anaphylaxis and hormonal disturbances. The most recent relevant research advances on glucose metabolism, liver function, cardiac function, renal function, sepsis, inflammation, infection, anaphylaxis and hormonal aspect are hereby reviewed. PMID- 26665884 TI - [Research Progress on Forensic Toxicology of Z-drugs]. AB - The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of gamma-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine. PMID- 26665885 TI - Acute Pharyngeal Hemorrhage as a Fatal Complication Arising from Acupotomy with Needle-knife: A Case Report. PMID- 26665886 TI - Celebrate W.Va.'s hidden health heroes. PMID- 26665887 TI - Medical Liability Pitfalls of EMR's/EHR's. PMID- 26665889 TI - The Public Health Impact Task Force: West Virginia's Call to Action. PMID- 26665890 TI - Colorectal Cancer Screening Challenges in West Virginia. PMID- 26665888 TI - Why this West Virginia Trained Physician Moved to Wyoming. PMID- 26665891 TI - Earlier Access to Hospice Care Might Improve End-of-Life Care for West Virginia's Elders. PMID- 26665892 TI - Primary Care Fall Risk Assessment for Elderly West Virginians. AB - West Virginia is ranked second nationally for the percent of its population 65 years of age. The elderly are especially susceptible to falls with fall risk increasing as age increases. Because falls are the number one cause of injury related morbidity and mortality in the West Virginia elderly, evaluation of fall risk is a critical component of the patient evaluation in the primary care setting. We therefore highlight fall risk assessments that require no specialized equipment or training and can easily be completed at an established office visit. High quality clinical practice guidelines supported by the American Geriatric Society recommend yearly fall risk evaluation in the elderly. Those seniors at greatest risk of falls will benefit from the standardized therapy protocols outlined and referral to a balance treatment center. Patients with low-to moderate fall risk attributed to muscle weakness or fatigue should be prescribed lower extremity strengthening exercises, such as kitchen counter exercises, to improve strength and balance. PMID- 26665893 TI - An Atypical Presentation of Pheochromocytoma. PMID- 26665894 TI - Primary Care Management of Plantar Fasciitis. AB - Plantar fasciitis (PF) is present in 10% of the population and is the most common cause of plantar heel pain. PF is painful, can alter daily activities and presents as a sharp pain localized to the plantar foot and medial heel. The underlying etiology involves microtrauma to the plantar fascia, specifically at its insertion point on the calcaneus. Successful management of plantar fasciitis is typically achieved with the conservative therapy approaches discussed. PMID- 26665895 TI - Myeloid Sarcoma of the Bladder in the Setting of Refractory Anemia with Excess Blasts-2 (RAEB-2). AB - Myeloid sarcoma is an extramedullary tumor consisting of immature hematopoietic cells of granulocytic or monocytic differentiation. While rare, it can be seen in a variety of clinical settings and is most commonly associated with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). We present a rare case of myeloid sarcoma occurring in the bladder of a 56 year old male. Myeloid sarcoma may be difficult to recognize due to its rarity and clinical and morphologic similarity to many other conditions; however, swift diagnosis is necessary as it is considered equivalent to AML. Prognostic indicators for myeloid sarcoma have not been well established, but survival may be improved by undergoing chemotherapy designed to treat AML. PMID- 26665897 TI - Hard truths, orthodontics, science and more. PMID- 26665896 TI - Update: Telemedicine. PMID- 26665898 TI - Health matters. PMID- 26665899 TI - Letter to the Editor. PMID- 26665902 TI - Understanding the IOTN. PMID- 26665901 TI - Public defender. PMID- 26665903 TI - Great expectations. PMID- 26665904 TI - Case report: drug-induced gingival overgrowth associated with the use of a calcium channel blocker (amlodipine). AB - INTRODUCTION: Many factors can contribute to the development of gingival overgrowth (hyperplasia), including: plaque control; periodontal variables; medications and their relative dose; age; sex; and, genetic factors. Nifedipine is a calcium channel blocker commonly reported to result in drug-induced gingival overgrowth (DIGO). This report outlines a case of gingival overgrowth induced by amlodipine (a calcium channel blocker less frequently reported to cause gingival hyperplasia), exacerbated by the presence of plaque. CASE REPORT: A 63-year-old male presented to the dental outpatient clinic at the Dublin Dental University Hospital with severe DIGO. He reported that his gums had started to enlarge two years previously, but that he was now concerned as they were increasing in size and had become firmer. Medically, the patient had hypertension, hyperlipidaemia, was taking amlodipine 10mg once daily, and was a former smoker. Following initial oral hygiene instruction and local debridement to reduce the gingival inflammation, some of the remaining excess gingival tissues were removed surgically and sent for histopathological analysis. DISCUSSION: Two possible causative agents were identified as: (i) amlodipine medication; and, (ii) poor plaque control. The removal of the pedunculated lump mesial to tooth 1-3 and the hyperplastic mandibular gingiva allowed for definite histopathological analysis of "fibroepithelial overgrowth showing moderate chronic inflammation". Following the excisional biopsies there was improved access for professional and at home cleaning, in addition to an improved aesthetic outcome. CONCLUSION: It is important that we are aware that individuals taking calcium channel blockers need to demonstrate excellent plaque control to reduce their risk of developing DIGO, and to reduce its severity should it arise. PMID- 26665906 TI - Making our voices heard. PMID- 26665905 TI - Fundamentals of occlusion and restorative dentistry. Part II: occlusal contacts, interferences and occlusal considerations in implant patients. AB - This second part of the two-part article discusses different types of occlusal contacts and their interferences. It also provides a practical guide to what is required to optimise the restorative treatment outcome. Occlusion and its effect on dental implants are also presented. CLINICAL RELEVANCE: Restorative treatment outcome is highly dependent on the occlusion of the restoration when the treatment is complete., PMID- 26665908 TI - Highlighting coordinated efforts to prevent surgical fires. PMID- 26665907 TI - [Genetic Polymorphisms of 26 Y-STR Loci in Fujian She Nationality and Its Forensic Application]. AB - OBJECTIVE: To study the forensic application of Goldeneye DNA ID 26Y Kit in the She nationality. METHODS: Through capillary electrophoresis, the genotype of 26 Y STR loci were analyzed in 53 unrelated male individuals from Fujian She nationality. The population genetics parameters such as allele frequency and haplotype diversity were calculated. The comparisons among the She nationality and the other nationalities were analyzed. RESULTS: A total of 126 alleles were observed on the 26 Y-STR loci of 53 unrelated male individuals. The allele frequencies and GD value ranged from 0.010 1 to 0.886 8 and 0.211 2 to 0.846 2, respectively. The GD value was greater than 0.5 in the 19 loci. A total of 47 haplotypes were observed. Based on R(ST), multidimensional scaling plot indicated that the genetic relationship among Fujian She nationality and Minnan Han nationality was closest, followed by Southern China Han nationality and Northern China nationality. CONCLUSION: GoldeneyeTM DNA ID 26Y Kit including 26 Y-STR loci has good polymorphism in the She nationality. As an additional system, it has forensic application value in some special cases. PMID- 26665909 TI - New guidance for reprocessing medical devices. PMID- 26665910 TI - Prevention of unplanned patient hypothermia. PMID- 26665911 TI - A tailored approach to fire safety in the OR. PMID- 26665912 TI - Factors associated with unprotected anal intercourse in gay men's casual partnerships in Sydney, Australia. AB - We assessed the factors associated with unprotected anal intercourse in gay men's casual partnerships, using data from a longitudinal cohort study ongoing since October 1992. Participants were recruited through gay community and a variety of other sources and interviewed for the Sydney Men and Sexual Health study. Of 1,037 interviewees at outset, 834 men had casual partners during the six months prior to interview; 609 had any anal intercourse with a casual partner. Of 172 HIV-positive men, 58 (33.7%) engaged in unprotected anal intercourse with casual partners. Of 662 non-positive men, 111 (16.8%) engaged in unprotected anal intercourse with casual partners. Logistic regression analysis revealed that gay men's engagement in unprotected anal intercourse with casual partners (compared with engagement in safe sex--either no anal intercourse or protected anal intercourse) was predicted by positive HIV status, occupational differences (being out of the workforce or in white collar positions rather than in professional or managerial positions), engagement in a wider range of anal practices, believing withdrawal to be safe and less favourable attitudes towards condoms. Additional logistic regressions which, initially, excluded positive men who only engaged in unprotected anal intercourse with positive casual partners (n = 26) and then excluded men who did not engage in anal intercourse (n = 225) yielded quite similar sets of predictors of unprotected anal intercourse with casual partners. However, in both the additional analyses HIV status was not a significant predictor. It is concluded that gay men who engage in unprotected anal intercourse with casual partners do not comprise a singular group, although they commonly engage in a diversity of anal practices and they dislike condoms. PMID- 26665913 TI - Age and injecting drug use revisited: the Australian Study of HIV and Injecting Drug Use. AB - In 1991 we reported on differences between younger and older injecting drug users (IDUs) in the Australian National AIDS and Injecting Drug Use Study. In 1994, a second large multi-city study of IDUs, the Australian Study of HIV and Injecting Drug Use (ASHIDU) allowed a repetition of that analysis to see whether age differences demonstrated in 1991 could still be found. Using discriminant function analysis, we found that younger (under 23) IDUs were more likely than older ID Us to be female, to have used hallucinogens in the previous month and to have used condoms during the last sexual encounter; and less likely to be in drug treatment. Young IDUs were more mobile, injected in larger groups, had had fewer HIV/AIDS tests, and used tranquillizers less frequently than older IDUs. These differences are similar in some respects to those found in 1991, but there were no differences in needle sharing as were found in 1991. The social context of younger IDUs' lives and drug use, and the difficulty in accessing them through drug treatment agencies are noted as factors to be taken into consideration when designing harm reduction strategies for this group. PMID- 26665914 TI - The impact of socio-economic factors, mental health and functional status on survival in a sample of AIDS patients. AB - The aim of the paper is to examine the influence of socio-economic conditions, mental health and functional status on survival of a sample of people with AIDS. It is a longitudinal prospective study carried out in five infectious disease wards in Rome and Naples, Italy. Patients enrolled (total 168) are all diagnosed as having AIDS in 1992. The Functional Multidimensional Evaluation Questionnaire for people infected with HIV was administered to all subjects. It collects information on social and economic conditions, physical and mental health, self sufficiency in Activities of Daily Living (ADLs) and on the demand for and/or utilization of a package of non-hospital care services. In the overall assessment, 11.3% of patients had inadequate socio-economic resources to cover their needs. More than half of those interviewed were partially or totally dependent on help to perform ADLs. There was a high prevalence of psychiatric symptoms (60.6%). Lower CD4 count and lower ability to perform ADLs were related to shorter survival with a mortality risk ratio by Cox regression of 1.5 (95 CI 1.2-1.9) and 1.6 (95 CI: 1.1-2.3), respectively. A lower ADL performance level was also associated with a higher prevalence of psychiatric symptoms and reduced socio-economic circumstances. The ADL performance level could be a useful predictor of survival in people with AIDS. There was, moreover, a marked association between functional status, socio-economic resources and mental health. The results support the hypothesis that these three factors have an impact on the survival of AIDS patients. PMID- 26665915 TI - Genitourinary Medicine staff knowledge about the risks of specific sexual behaviours in the transmission of HIV. AB - The aim of this study was to investigate the consistency of information about HIV sexual transmission provided by genitourinary medicine (GUM) staff to their patients. This staff group's knowledge of specific sexual risk behaviours was obtained using a self-administered anonymous 21-item questionnaire. Results for 106 respondents revealed considerable inconsistency amongst GUM staff's risk ratings of different sexual activities. These inconsistencies in risk ratings were significantly related to profession and gender. The results are discussed in terms of the lack of available consistent information about oral sex as well as less conventional sexual activities. The results support the need for a strategy to ensure the provision of clear and consistent messages about the sexual transmission of HIV. Any sexual health promotion strategy within GUM clinics needs to review and audit the quality of information given by health professionals to patients. PMID- 26665916 TI - What informal caregivers actually do: the caregiving skills of partners of men with AIDS. AB - This study draws on the narrative accounts of caregiving events provided by 100 HIV-negative and HIV-positive partners of men with AIDS during their partners' illness. The narratives contain rich detail about the wide range of skills that these men developed over the course of their caregiving. These skills, which go beyond the kinds of assistance with daily activities that normally comprise caregiving assessments, pertain to the provision of emotional support, hands-on care, clinical care, high tech nursing and health care advocacy. Because these narratives depict caregiving in its naturally occurring context, it is also possible to describe ways in which the context of caregiving, including the partners' relationship, the clinical course of the illness and changes in the meaning of the illness, influence the development of these caregiving skills. Finally, the narratives provide insight not only into the burdens of care, but also into its often overlooked positive aspects. PMID- 26665917 TI - Condoms: mis-use = non-use. The condom equation in Gujarat, India. AB - Condoms are a common denominator for three prestigious national prevention programmes in India, none of which has been a real success. The present study was undertaken to investigate prevalence of condom use and to assess knowledge about correct use of condoms among married, sexually active men, who had not adopted any permanent method of contraception. The study was conducted by a house-to house survey in eight randomly selected villages of Anand, Gujarat (a 10% sample). All married men (ages: 18-55 years) were interviewed with the help of a pre-tested, structured questionnaire, comprising questions on: (a) their sexual practices; (b) knowledge about the correct use of condoms; and (c) reasons for their use/non-use. Respondents were evaluated for knowledge about correct use of condoms by scoring on a scale of 10. The sample consisted of 1,478 men whose mean age was 29.8 (+/- 6.75) years and mean duration of married life was 8.4 (+/- 6.25) years. Almost 52% (n = 771) were either illiterate or had been educated up to primary level; while 131 (8.8%) had university qualifications. More than 74% (n = 1,092) had never used condoms; 24.4% had used them irregularly and only 1.8% (n = 26) were using them regularly. The mean knowledge score for the correct use of condoms was 1.44 +/- 2.29 on a scale of 10 and it was positively related to regularity of use and educational status of respondents (p < 0.001). Sixty-nine percent of the respondents did not know that condoms offer protection against STDs and/or AIDS. The most common mistakes related to incorrect use of condoms were use of oil-based lubricants with condoms, ignorance about the technique of putting on a condom, re-use of condoms, etc. The commonly cited reasons for non use of condoms were interference with sexual activity; lack of privacy; fear of losing it inside the woman's body, and lack of confidence in its effectiveness as a contraceptive. To be effective as a contraceptive and to offer protection against sexually transmitted diseases and AIDS, condoms need to be used regularly and correctly. Distribution of condoms should be coupled with education about their correct use, and efforts should be made to dispel myths and misbeliefs associated with their use. PMID- 26665918 TI - Sexual behaviour change associated with a college HIV course. AB - This study examined the effects of a multidisciplinary, multi-media college course, The HIV Pandemic and AIDS, on the knowledge, attitudes and behaviours of students. A quasi-experimental design was implemented using pre- and post questionnaires administered to students enrolled in the course and to two control groups (N = 131) similar in age, gender, degree programme and class. At pre testing, over 80% of students involved in relationships of four months or more reported having genital intercourse without a condom occasionally or frequently in the last year. Post-test results indicated HIV course participants changed more risk-related behaviours and felt less vulnerable to contracting HIV than the control group. Significant differences reported by course-enrolled students in comparison to the control group included discussing safe sex with a potential partner at a higher rate, becoming more selective about partners, and learning more about HIV. The dangers of presumed monogamy are discussed in relation to the transtheoretical model of change and the development of future HIV courses. PMID- 26665919 TI - WHO Global AIDS Statistics. AIDS cases reported to the World Health Organization as at 30 June 1997. PMID- 26665920 TI - [Horn shaped perforator flap pedicled with the angular artery: anatomy basis and clinical application]. AB - OBJECTIVE: To explore the anatomic basis and clinical application of the horn shaped perforator flap pedicled with the angular artery for the reconstruction of midface defect. METHODS: (1) 10 fresh cadavers were perfused with a modified guiding oxide gelatin mixture for three-dimensional visualization reconstruction using a 16-slice spiral computed tomography scanner and specialized software (Materiaise' s interactive medical image control system, MIMICS). The origin and distribution of the angular artery perforator were observed. (2) Between July 2012 and July 2014, twenty-one patients underwent operations for the reconstruction of midface defect. Ten patients had squamous cell carcinoma, nine patients had basal cell carcinoma and two patients had nevus. The flaps' size ranged from 1.5 cm x 3.5 cm to 2.5 cm x 5.0 cm. RESULTS: The facial artery branches the lateral nasal artery 1 cm from the outside corner of the mouth, subsequently strenches to inner canthus continuing as the angular artery. The angular artery anastomoses extensively with the dorsal nasal artery and the infraorbital artery. All the flaps survived. The patients were satisfied with the final aesthetic and functional results. CONCLUSIONS: The flap can be designed flexibly and simply with reliable blood supply. The donor sites could be closed directly without skin graft, it is a simple and fast method for the reconstruction of midface defect. PMID- 26665921 TI - [Preliminary clinical research with thoracic deformities in microtia]. AB - OBJECTIVE: To investigate the characteristics and incidence of the thoracic deformities in patients with microtia. METHODS: In Plastic Surgery Hospital, we conducted a retrospective study of the clinical and radiographical data of 300 patients with microtia from March 2013 to October 2014. Pearson chi2 test was used to analyze the relationship among deformities of ribs and spine, as well as microtia. RESULTS: A total of 78 (26.0%) patients were documented with rib deformities, 26 patients (8.7%) had spinal deformities, and 17 patients (5.7% )had both. The incidence of rib deformities in microtia I, II, and III was 7.1% (2/28), 26.7% (62/232) and 35.0% (14/40) respectively. The incidence of spinal deformities in microtia I, II, and III was 3.6% (1/28), 6.5% (15/232) and 25.0% (10/40 respectively. The patients with microtia III were found to have a higher incidence of ribs and spinal deformities than those with microtia II, patients with microtia II were found to have a higher incidence of ribs and spinal deformities than those with microtia I (P < 0.05). CONCLUSIONS: The incidence of ribs and spinal deformities is high in patients with microtia. The poorer one auricle developed, the higher the incidence of thoracic deformities. PMID- 26665922 TI - [Total auricular reconstruction with single big expander at dual plane through incision at remnant ear]. AB - OBJECTIVE: To investigate the feasibility and advantages of total auricular reconstruction with single big expander at dual plane through incision at remnant ear. METHODS: 52 patients with microtia were treated. Through incision at remnant ear, one big expander (150 ml) was implanted in the post-auricular area beneath the superficial facial in the hairless area, and above the superficial fascia in the area with hair. In the second stage, total auricular was reconstructed with autologous cartilage framework and expanded skin. Skin graft was not necessary. Another 32 paitents with single big expander above the superficial fascia were used as control. The downward shift distance of expanders, the appearance of auriculocephalic sulcus and complication were recorded in order to assess the effect of these two methods. RESULTS: The downward shift distance of expanders in the dual plane group (0.7 +/- 0.3) cm were lower than that in the control group (1.3 +/- 0.4) cm, showing significant difference (P < 0.05). After a follow-up period of 6-12 months, shallow auriculocephalic sulcus was presented in 5 patients of the dual plane group and 12 patient of the control group. The shallow auriculocephalic sulcus was cut to make it deeper and covered with full skin graft. CONCLUSIONS: Dual plane skin expansion could reduce the downward shift distance of expander. Adequate skin on the upper part of expander could make satisfactory auriculocephalic sulcus. PMID- 26665923 TI - [Analysis of HOXD13 gene in polydactyly in dispersion type]. AB - OBJECTIVE: To analyze HOXD13 gene in polydactyly in dispersion type of Fujian Han population in order to know whether there is mutation in HOXD13. METHODS: All members were evaluated physically and radlologically. Genomic DNA was extracted from peripheral blood of the patients who were treated from Dec. 2012 to Apr. 2013, their parents, grandparents, and normal volunteers from our department. The polymerase chain reaction ( PCR) , agarose gel electrophoresis and DNA sequence analysis were adopted to analyze HOXD13 from six cases with polydactyly and forty normal volunteers. RESULTS: All patients had no family history. A heterozygous synonymous mutation, c. 291 C > T( p. A60A), was detected in exon 1 of the HOXD13 Gene in five of the polydactyly patients. Similar mutation was not detected in one brachy dactyly patient and the forty normal volunteers. CONCLUSION: A heterozygous synonymous mutation, c.291C > T (p. A60A), of the HOXD13 gene may be related with polydactyly in dispersion type of Chinese han population. PMID- 26665924 TI - [Application of MRI in the diagnosis of glomus tumor]. AB - OBJECTIVE: To discuss the necessity of MRI as a routine examination for diagnosis of glomus tumor. METHODS: From Nov. 2013 to July 2014, 7 cases of glomus tumor were treated in our department. All patients had typical clinical symptoms of glomus tumor and received preoperative X-ray and/or MRI examination. The diagnosis was confirmed by postoperative histopathologic examination. All the patients were retrospectively analyzed by reviewing the preoperative examination results and PubMed search results. RESULTS: 2 cases underwent only X-ray examination before operation with no positive results. 3 cases underwent both X ray and MRI. No positive finding happened in X-ray, while MRI showed glomus tumor characteristic on T1- and T2-weighted images which demonstreated a more intense signal after injection of gadolinium. The last 2 cases underwent only MRI examination, which revealed positive images of glomus tumor. CONCLUSIONS: MRI plays an important role in diagnosis of glomus tumor and should be adopted as a routine examination. PMID- 26665925 TI - [Comprehensive therapy for infant vascular tumor associated with Kasabach-Merritt phenomenon]. AB - OBJECTIVE: To summarize the management of infant vascular tumors with Kasabach Merritt phenomenon (KMP) and to evaluate the effect of drug combined with sclerotherapy. METHODS: From Feb. 2007 to Nov. 2014, 25 cases with KMP, who underwent drug therapy combined with sclerotherapy, were retrospectively studied. Oral corticosteroids (2 mg/kg per day) was used as the first-line therapy on all of the patients and intravenous vincristine (1.5 mg/m2 every week) was added when the platelet counts didn't recover obviously after 2-3 weeks. After the recovery of the platelet counts, the patients were admitted for sclerotherapy (average, 4.56 sessions per case) with 100% alcohol (1-3 ml per session), Lauromacrogol (1.25-5 ml per session) and betamethasone (0.25-1 ml per session). All the patients were followed up for 42 months ( range, 9 months to 6.5 years). Therapeutic outcomes were assessed by evaluating platelet counts, size of lesion, function of trunk and limb. RESULTS: All the 25 cases got obvious recovery in the platelet counts [average, (94.3 +/- 18.5) x 10(9)/L] after drug therapy, of which 16 were treated by single oral corticosteroids for 4-7 weeks and 9 were treated by corticosteroids plus intravenous vincristine for 2-5 weeks. Meantime, 11 cases received platelet transfusions, of which 3 were coupled with gamma globulin intramuscularly. During the first admission, each of the 25 cases received 1-4 sessions of sclerotherapy (average, 2.6 sessions each case). One week after the sclerotherapy, the platelet counts returned to (167-312) x 10(9)/L (average, (258.5 +/- 34.4) x 10(9)/L). The hemoglobin and blood coagulation function returned to normal within 1-5 weeks. Meanwhile the mental condition, appetite, body weight, sleeping were greatly improved. The size of the lesions decreased gradually after the combined therapy including 13 cases within 3-12 months and 13 cases within 13-36 months. Long term follow-up indicated that only 1 case need treatment for recurrent decrease of platelet counts, and all of the 25 cases kept the normal weight, height, immunity as well as the growing development. CONCLUSIONS: Oral corticosteroids plus intravenous vincristine combined with sclerotherapy is a reliable management with high cure rate, short course and minor side-effect. PMID- 26665926 TI - [Effect of propranolol gel on plasma VEGF, bFGF and MMP-9 in proliferating infantile hemangiomas of superficial type]. AB - OBJECTIVE: To investigate the effect of topical propranolol gel on the levels of plasma vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) and matrix metalloproteinases-9 (MMP-9) in proliferating infantile hemangiomas (IHs) of superficial type. METHODS: 33 consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma VEGF, MMP-9 and bFGF by enzyme linked immunosorbent assay (ELISA) in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants. The clinical efficacy in IHs was evaluated by Achauer system. Differences of plasma results between the healthy group and the IHs group pre-treatment were analyzed using Mann-Whitney U-test. Paired sample comparisons of any two time points of pre-treatment, 1 month and 3 months after treatment in IHs were evaluated by Wilcoxon signed-rank test. RESULTS: The clinical efficiency of topical propranolol gel at 1, 3 months after application were 45.45%, 81.82% respectively. The levels of plasma VEGF and MMP-9 in patients pre- treatment were higher than those in healthy infants [(362.16 +/- 27.29) pg/ml vs (85.63 +/- 8.14) pg/ml, (1376.41 +/- 42.15) pg/ml vs (687.27 +/- 44.1) pg/ml, P < 0.05], but the level of bFGF did not show significant difference [(176.03 +/- 13.60 ) pg/ml vs (235.94 +/- 35.43 ) pg/ml, P > 0. 05 ]. The concentrations of VEGF and bFGF at 1, 3 months after treatment decreased obviously [(271.51 +/- 18.59) pg/ml vs (362.16 +/- 27.29 ) pg/ml, (135.85 +/- 12.66) pg/ml vs (176.03 +/- 13.60) pg/ml], 1 month after treatment vs pre treatment, P < 0.05; (240.80 +/- 19.89) pg/ml vs (362.16 +/- 27.29) pg/ml, (107.31 +/- 5.82) pg/ml vs (176.03 +/- 13.60) pg/ml, 3 month after treatment vs pre-treatment, P < 0.05, whereas the levels of plasma MMP-9 declined slightly [(1321.18 +/- 48.74) pg/ml vs (1376.41 +/- 42.15 ) pg/ml, (1468.68 +/- 32.78) pg/ml vs (1376.41 +/- 42 2.15 ) pg/ml, P > 0.05 ]. CONCLUSIONS: Propranolol gel may suppress the proliferation of superficial infantile bemangiomas by reducing VEGF and bFGF. PMID- 26665927 TI - [Application of radiofrequency ablation for tongue venous malformation]. AB - OBJECTIVE: To explore the therapeutic effect of radiofrequency ablation for tongue venous malformation( VM). METHODS: From July 2013 to July 2014, 30 cases with tongue VM (local or diffuse) were retrospectively analyzed. 23 cases underwent radiofrequency ablation treatment. The radiofrequency electrode tip(0. 5 mm in diameter) was inserted into the lesion 1 mm below the bottom with 25 W in power and 15-30 s of pulse. The treatment was repeated when the electrode tip was removed back every 1 mm. Multi-point treatment was performed. RESULTS: 15 cases with unilateral VM were completely healed after one-stage radiofrequency ablation. 8 cases with bilateral VM received two-stage radiofrequency ablation with a 3-6 months of interval. Among the 8 cases, completely healing was achieved in 5 cases, partial VM residue happened in 3 cases due to its diffuse lesion and reservation of tongue function. 23 cases were followed up for 3 month to 1.5 years. Good cosmetic and functional results was achieved in 20 cases with no relapse. Partial VM residue was left in 3 cases. CONCLUSIONS: Radiofrequency ablation can effectively treat tongue VM with minimal morbidity and good cosmetic appearance. It also avoids the disadvantages of surgery. PMID- 26665928 TI - [Reconstruction of tibial exposure with local muscular flap, VSD and skin transplantation]. AB - OBJECTIVE: To investigate the treatment for tibial exposure wounds. METHODS: 39 patients with tibial exposure wounds were divided into three groups according to the exposure location (upper, medium and below). The local muscular flaps were designed to cover the tibial exposure, followed by skin grafts and VSD. VSD was removed one week later. RESULTS: All the muscular flap and skin graft survived. Mild epidermis erosion happened in 2 cases, which healed spontaneously after dressing. The patients were followed up for 3-6 months with good healing and no walking malfunction. CONCLUSIONS: The local muscular flap combined with skin graft and VSD is a simple and effective method for tibial exposure wound with short healing time and high successful rate. PMID- 26665929 TI - [Endoscopic transaxillary surgery for congenital muscular torticollis]. AB - OBJECTIVE: To investigate a new endoscopic transaxillary technique for release of the sternocleidomastoid (SCM) in congenital muscular torticollis (CMT). METHODS: From May 2008 to March 2014, a total of 25 cases (male 7 and female 18), ranging in age from 14 to 31 years (mean age, 17.6 years), were operated for torticollis by endoscopic-assisted surgery. The sternal and clavicular attachments of the sternocleidomastoid were released by skin lift approach. RESULTS: The primary healing was achieved in all the 25 cases with no injury of major vessels or nerves. The patients were followed up for 6 months with satisfactory result and invisible scar. CONCLUSIONS: The subcutaneous endoscopic transaxillary and skin lift approach for the CMT provides good functional and cosmetic outcomes. PMID- 26665930 TI - [The treatment of upper eyelid sulcus using the expanded polytetrafluoroethylene implanted in orbit]. AB - OBJECTIVE: To explore the feasibility of the treatment of upper eyelid sulcus using the expanded polytetrafluoroethylene implanted in orbit. METHODS: From July 2009 to April 2011, a total of 16 patients with upper eyelid sulcus were treated for recreating youthful periorbital appearance. To correct this kind of clinical characteristic, expanded polytetrafluoroethylene with different size were used as the orbital implant to restore the orbital contents and reinforce the bony support. upper eyelid sulcus was reversed effectively. RESULTS: With average 2.5 year follow up, upper eyelid sulcus of 16 cases was reversed effectively. No postoperative complication related to globe or affected normal physical function was found. CONCLUSIONS: The technique of orbital implantation with Expanded Polytetrafluoroethylene is beneficial for the treatment of the upper eyelid sulcus. PMID- 26665931 TI - [Reconstruction of small skin defect on children heel with V-Y advanced flap pedicled with perforator of peroneal artery at posterior lateral malleolus]. AB - OBJECTIVE: To investigate the therapeutic effect of V-Y advanced flap pedicled with perforator of peroneal artery at posterior lateral malleolus for small skin defect on children heel. METHODS: From Mar. 2012 to Jan. 2014, 9 children with small skin defects on heel were treated with adjacent V-Y advanced flap pedicled with perforator of peroneal artery at posterior lateral malleolus. The flaps were 8.0 cm x 4.0 cm to 9.0 cm x 4.5 cm in size and the wounds at donor sits were directly closed. RESULTS: All flaps survived completely with primary healing. 9 cases were followed up for 6-12 months( average, 9 months). The flaps had good match with surrounding tissue in texture and color. The function of ankle was normal. All the parents were satisfied with functional and cosmetic results. CONCLUSIONS: It is a safe and practical method for treatment of small skin defect on children heel with adjacent V-Y advanced flap pedicled with perforator of peroneal artery at posterior lateral malleolus. PMID- 26665932 TI - [The effect of Metformin on the proliferation and collagen synthesis of human keloids fibroblasts]. AB - OBJECTIVE: To investigate the effect of Metformin on the proliferation and collagen synthesis of the human keloids fibroblasts as well as the effect on phosphorylation of Akt/FoxO1 signal transduction pathway. METHODS: Fibroblasts of keloid were divided into control group treated with medium solution and experimental groups treated with different concentrations of Metformin. 48 h later CCK-8 assay was adopted to evaluate cell survival; Western blot was performed to detect the Akt and FoxO1 phosphorylation; and Hydroxyproline reagent kit was used to detect the collagen synthesis. RESULTS: With different concentrations (30, 60, 90, 120 mmol/L) of Metformin, the absorbance of cultured keloid fibroblasts detected by CCK8 assay decreased by (13.30 +/- 2.04)%, (22.64 +/- 4.70)%, (54.00 +/- 5.34)% and (63.12 +/- 3.48)%. The growth of fibroblasts was suppressed by Metformin in a dose-dependent manner. It showed that the level of phoshpo-akt and phoshpo-foxOl in keloids fibroblasts in experimental groups was lower than that in the control group and the collagen synthesis were also decreased in experimental groups, all in a dose-dependent manner (P < 0.05, P < 0.01). CONCLUSIONS: Metformin can effectively inhibit the proliferation and collagen synthesis of the human keloids fibroblasts in vitro, which may be associated with the suppression of phosphorylation of Akt/FoxO1 signaling pathway PMID- 26665933 TI - [The study of anticoagulants selection in platelet-rich plasma preparation]. AB - OBJECTIVE: To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. METHODS: The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF beta1 release amount of activated PRP of four groups was measured. RESULTS: CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-beta1 compared with heparin and citrate. CONCLUSIONS: The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level. PMID- 26665934 TI - Therapeutic Application of Bone Marrow-Derived Stem Cells in a Patient with Methanol-Induced Blindness. AB - OBJECTIVE: To report bone marrow derived stem cell application in a patient with bilateral visual loss due to accidental ingestion of methanol. METHOD: A 22-year old male patient with bilateral visual loss at discharge after treatment for methanol ingestion was treated with retrobulbar and intrathecal autologus bone marrow derived stem cells in an outpatient setting. The procedure was followed by Vit B12 Injection 500 mcg alternate days and oral vitamins B1, B2, B6, in therapeutic dose for 3 months. RESULT: The patient demonstrated favorable outcome three days after the treatment. Visual acuity improved to 20/20 in both eyes by third week. CONCLUSION: Treatment with retrobulbar and intrathecal autologous bone marrow derived stem cell in an adult male patient with bilateral visual loss due to accidental ingestion of methanol was effective. Larger studies are warranted to explore the real impact of this procedure. PMID- 26665935 TI - Hematopoietic Stem Cells, Their Niche, and the Concept of Co-Culture Systems: A Critical Review. AB - Hematopoietic stem cells (HSCs) have the ability to self-renew and give rise to all lineages of blood cells. HSCs reside in niches that are local tissue microenvironments that maintain and regulate them. Although much progress has been made in elucidating the location and cellular components of the HSC niche, however it still remains incompletely defined. Transplantation using HSCs has been applied for the treatment of several diseases but with limited success. Furthermore, although human HSC transplantation has been widely used to rescue the patients after cytoablative therapies, quantitative in vivo human assays for hematopoietic cells have been considered to be neither ethical nor practical. Since HSCs persist in small quantities in the body, understanding the mechanism that govern their fate is essential for the advancement of HSC expansion and transplantation in the future. Since bone marrow is the primary site of HSC maintenance and hematopoiesis, defining the niche components that work in concert to regulate hematopoiesis is crucial to improve regeneration following injury or following HSC transplantation and to also understand how disordered niche function could contribute to disease. In recent years, there has been a growing realization of the limitations in identifying the primitive HSCs by its phenotype alone and therefore the concept of co-culture systems (functional in vitro assays) has become increasingly important to demonstrate the presence of primitive hematopoietic cells by estimating their biological functions. This system has provided a basis for the development of powerful assay procedures for expanding, quantitating and distinguishing cells at discrete stages of early hematopoietic cell differentiation. PMID- 26665936 TI - Age, Sex, and Religious Beliefs Impact the Attitude towards Cord Blood Banking. AB - In this study, a self-administered questionnaire was used to assess opinions about stem cell research and cord blood banking. Three attitudes were examined: willingness to accept cord blood banking, willingness to accept embryonic stem cell research, and religious belief system. A total of 90 Wayne State University students enrolled in the study in response to an invitation posted on a web page for the university. Sex distribution among study participants was 79 females and eight males; three declined to state their sex. Support for cord blood banking was high (> 70%) among students. Students over the age of 25 years of age were more (85%) positive than students 18 to 24 years old (57%). They prefered a public cord blood bank over a private cord blood bank. Atheist/agnostic or spiritual/not religious students (> 90%), Catholic students (78%) and Christian students (58%) support cord blood banking. Age, sex and religion seems influence the student's attitude towards stem cell research and cord blood banking. PMID- 26665937 TI - Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs). AB - Induced Pluripotent Stem Cells (iPSCs) are self renewable and can differentiate to different types of adult cells, which has shown great promises in the field of regenerative medicine. iPSCs are reprogrammed from human somatic cells through ectopic expression of various transcription factors viz. Oct4, Sox2, Klf4, and c Myc (OSKM). This novel technology enables derivation of patient specific cells, which possess a potential cure for many diseases. During the last decade, significant progresses have been achieved in enhancing the reprogramming efficiency, safety of iPSCs derivation, development of different delivery techniques by various research groups. Nevertheless, it is important to resolve and define the mechanism underlying the pluripotent stem cells. Major bottleneck which arises during iPSCs generation is the availability of source material (cells/tissues), difficulty to deliver transcription factors with no aberrant genetic modifications and limited reprogramming efficiency. Reprogramming may be achieved by employing different cocktails with number of different transcription factors, application of miRNA and some small molecules such as (Valproic acid, CHiR99021, Sodium butyrate, Vitamin C, Parnate etc). Similarly, various starting source materials have been demonstrated for iPSC based therapies including fibroblasts, cord blood, peripheral blood, keritinocytes, urine, etc., with their specific uses and limitations. Moreover, with the advent of many new reprogramming techniques, various direct delivery methods have been introduced such as using synthetic mRNA expressing pluripotent gene network has been shown to be an appropriate technique to deliver transcription factors and a dozen of small molecules which can replace transcription factors or enhance reprogramming efficiency. This article addresses the iPSCs technology mechanisms, progresses and current perspectives in the field. PMID- 26665938 TI - Mesenchymal Stem Cells and Lung Transplantation: A Couple for a Perfect Relationship. AB - With the increased incidence of lung and other organ failure, organ transplantation becomes a frequent surgical intervention. Research is focused on improving the practice of lung and other organ transplantation in order to improve the clinical outcome and to decrease the incidence of post-operative complications. This manuscript represents the author's view of the possibility of improving the lung transplantation outcome through the co-transplantation of mesenchymal stem cells, and the expected positive effects of that application. PMID- 26665939 TI - [Interference Detection and Signal Quality Assessment of Pulse Signals]. AB - Pulse signal contains a wealth of biological and pathological information. However, it is susceptible to the influence of various factors which results in poor signal quality, and causes the device to generate false alarms. First the pulse signals are processing into discrete symbols, and then compare the test signal with the pulse template by using Dynamic Time Warping (DTW) to get the threshold for which can be used to find the interference segment of the test signal. By analyzing the DTW distance of the pulse signal, we can get the interference degree of the signal, then the quality level of the plus signal can be defined by the relationship between the interference degree and quality of the signal. The 1 055 group pulse signals provided by MIMIC II physiological database are used to train and test the signal quality assessment algorithms, and compared with other existing algorithms. The results show that the algorithms can accurately detect interference segments in pulse signal and reflect the quality of it. PMID- 26665940 TI - [A Smart Low-Power-Consumption ECG Monitor Based on MSP430F5529 and CC2540]. AB - A design of ECG monitor was presented in this paper. It is based on the latest MCU and BLE4.0 technologies and can interact with multi-platform smart devices with extra low power consumption. Besides, a clinical expansion part can realize functions including displaying the real-time ECG and heart rate curve, reading abnormal ECG signals stored in the monitor, and setting alarm threshold. These functions are suitable for follow-up use. PMID- 26665941 TI - [Development of Non-Contact Monitoring Device for Breathing and Heartbeat]. AB - Physiological monitoring devices in modern clinical area are basically used electrodes or sensors directly touching the surface of human subject body, which will increase physiological and psychological load of the subjects. In order to realize non-contact monitoring of respiration and heartbeat, firstly, the micro bioradar was used to detect human body motion signal. Then, the respiration signal and heartbeat signal was extracted from the body-motion signal by using signal and conditioning circuits, digital filter and signal processing. Finally, the results of heart rate and breathing rate was wirelessly transmitted. The experimental results showed that the device for non-contact monitoring of respiration and heartbeat waveforms has advantages of small volume, low power consumption, which can realize the monitoring of physiological parameters in real time. PMID- 26665942 TI - [The Study of the Measurement of Heart Rate Variability Using ECG and Photoplethysmographic Signal]. AB - In comparison with the measurement of heart rate variability from ECG and from photoplethysmographic signal from 46 healthy adults in their spontaneous breathing state. The beat-to-beat intervals in ECG and pulse-to-pulse intervals in photoplethysmographic signal are extracted, and then the parameters of heart rate variability are calculated. Three kinds of algorithms are chosen to get the pulse-to-pulse intervals, which are the intervals of maximum of second derivative, the maximum of PPG signal and the tangent intersection. The results show that the correlation coefficients of the HRV parameters in the two calculation methods are highly correlated. The Bland-Altman scattered plots show the relative bias results from the algorithm of the maximum of PPG signal are smallest and singular points that deviate from the consistent limits are the least compared with the other two algorithms. PMID- 26665943 TI - [Real-time Gait Training System with Embedded Functional Electrical Stimulation]. AB - To solve the problem that mostly gait analysis is independent from the treatment, this work proposes a system that integrates the functions of gait training and assessment for foot drop treatment. The system uses a set of sensors to collect gait parameters and designes multi-mode functional electrical stimulators as actuator. Body area network technology is introduced to coordinate the data communication and execution of the sensors and stimulators, synchronize the gait analysis and foot drop treatment. Bluetooth 4.0 is applied to low the power consumption of the system. The system realizes the synchronization of treatment and gait analysis. It is able to acquire and analyze the dynamic parameters of ankle, knee and hip in real-time, and treat patients by guiding functional electrical stimulation delivery to the specific body locations of patients. PMID- 26665944 TI - [The Development of Information Centralization and Management Integration System for Monitors Based on Wireless Sensor Network]. AB - Developed the information centralization and management integration system for monitors of different brands and models with wireless sensor network technologies such as wireless location and wireless communication, based on the existing wireless network. With adaptive implementation and low cost, the system which possesses the advantages of real-time, efficiency and elaboration is able to collect status and data of the monitors, locate the monitors, and provide services with web server, video server and locating server via local network. Using an intranet computer, the clinical and device management staffs can access the status and parameters of monitors. Applications of this system provide convenience and save human resource for clinical departments, as well as promote the efficiency, accuracy and elaboration for the device management. The successful achievement of this system provides solution for integrated and elaborated management of the mobile devices including ventilator and infusion pump. PMID- 26665945 TI - [Design of the Mobile ECG Monitoring System Based on Android 4.3]. AB - To monitor and record Electrocardiograph (ECG) signals for 24 hours, a mobile ECG monitoring system is designed based on Android 4.3. In this system, domestic indigenous E9622A is used to acquire ECG signals and TI CC2541 is adopted to communicate with mobile phones. The program is implemented on the Android platform to display and process ECG signals. The whole system is integrated on a 2 cm x 2 cm PCB. From experiments, it is shown that ECG signals can be obtained effectively when this system is worn, and clear ECG waveforms and parameters can be shown on the phones. With this system, arrhythmia can be diagnosed preliminarily. It is also shown that the system is low-power, low-cost, flexible and portable. PMID- 26665946 TI - [Design of a Special Shaped Foam Dressing Based on Anatomy]. AB - As the dressings currently used in clinic settings unflat shape in general, they can't be fitted completely on occiput, heel, elbow, knee and other body parts unflat. This paper developed one kind of foam dressing of special shape based on local anatomy. The foam dressing is waterproof and air permeable, it can cover the wound closely enough to prevent bacteria from invasion and infection. With a saturated absorption ratio of 1: 8 or higher, it can keep the wound clean and moisture by absorbing large amounts of wound inflammatory secretions and is almost completely permeable to oxygen and carbon dioxide. Assuring safety and effect meanwhile, it has better outcomes than common dressings in the same application settings. PMID- 26665947 TI - [Design of an Incremental and Open Laboratory Automation System]. AB - Recent years have witnessed great development of TLA (Total Laboratory Automation) technology, however, its application hit the bottleneck of high cost and openess to other parties' instruments. Specifically speaking, the initial purchase of the medical devices requires large sum of money and the new system can hardly be compatible with existing equipment. This thesis proposes a new thought for system implementation that through incremental upgrade, the initial capital investment can be reduced and through open architecture and interfaces, the seamless connection of different devices can be achieved. This thesis elaborates on the standards that open architecture design should follow in aspect of mechanics, electro-communication and information interaction and the key technology points in system implementation. PMID- 26665948 TI - [Consideration of Mobile Medical Device Regulation]. AB - The regulation of mobile medical devices is one of the hot topics in the industry now. The definition, regulation scope and requirements, potential risks of mobile medical devices were analyzed and discussed based on mobile computing techniques and the FDA guidance of mobile medical applications. The regulation work of mobile medical devices in China needs to adopt the risk-based method. PMID- 26665949 TI - [The Analysis on Application of Global Medical Device Nomenclature(GMDN)]. AB - The article has reviewed the administration technical structure and global application of the global medical device nomenclature(GMDN), analyzed the coordination between GMDN and the industry status of medical device in our country, put forward some suggestions on the applicaition of GMDN, provided some reference on raising the management level of medical device in our country. PMID- 26665950 TI - [Change of Regulatory Requirement on Cohort Grouping and Endpoint Seting for Intervertebral Fusion Device Clinical Trial]. AB - Combining technical requirement from main international administration and status quo of China administration, current regulatory requirement on clinical trail of conventional intervertebral fusion devices has been simplified. Cervical, thoracic and lumbar cases can be grouped into the same cohort, and primary endpoints are mainly based on imageology rather than clinical score. This is an attempt to rationally lessen industrial burdensome. PMID- 26665951 TI - [The Quality Analysis of National Supervising Sampling for Rubella Virus IgM Diagnostic Kits in 2014]. AB - OBJECTIVE: To evaluate the quality status of rubella virus IgM diagnostic kits by national supervising sampling. METHODS: Using legal inspection combining with exploratory study, the positive and negative coincidence rate, detection limit and repeatability of kits were verified. RESULTS: The results showed that 15 of 16 batches of kits were qualified using legal inspection, and the passing rate was 93.8%. The unqualified item was negative coincidence rate. In exploratory study, only 11 batches (68.8%) complied with industry standard. The unqualified items were negative coincidence rate, detection limit and repeatability. CONCLUSION: At present, rubella virus IgM diagnostic Kits have some quality problems in the market. It is recommended that we adopt industry standard and national reference panel in the registration inspection for the future, which will prompt enterprises to improve quality. PMID- 26665952 TI - [Mobile Health: IEEE Standard for Wearable Cuffless Blood Pressure Measuring Devices]. AB - IEEE Std 1708-2014 breaks through the traditional standards of cuff based blood pressure measuring devices and establishes a normative definition of wearable cuffless blood pressure measuring devices and the objective performance evaluation of this kind of devices. This study firstly introduces the background of the new standard. Then, the standard details will be described, and the impact of cuffless blood pressure measuring devices with the new standard on manufacturers and end users will be addressed. PMID- 26665953 TI - [PDCA Applied in Special Rectification of Medical Instrument Clinical Trial]. AB - PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P < 0.001), score rate of items increased except adverse events (P < 0.001). The special rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial. PMID- 26665954 TI - [A Preliminary Study on the Classification Regular Pattern of Non-Powered Suction Apparatus Device Intended for Negative Pressure Wound Therapy]. AB - The classification messages of non-powered suction apparatus device (NPSAD) intended for negative pressure wound therapy by CFDA have been analysis and generalized. A set of classification regular patterns of NPSAD have been generalized from its intended use, composition, mechanism, contact area and resorbable characteristic. It is helpful to draw a more consistent classification in NPSAD. PMID- 26665955 TI - [Comparative Study on Evaluating the Bladder Volume between BladderScan BVI9400 and Ultrasound System iU22]. AB - OBJECTIVE: To evaluate the accuracy of the latest BladderScan BVI9400 on measuring bladder volume. METHODS: Two bladder phantoms were selected for investigating the accuracy of BVI9400. 341 patients with the iU22 ultrasound examinations were followed by BVI 9400. The difference and correlation between BVI9400 and iU22 were contrastively analyzed. RESULTS: The relative difference between results from BVI9400 and phantom volume was 2.5% and 1.36%. There was a strong correlation for patients between BVI9400 and iU22 (R = 0.96, P < 0.001). The relative difference between BVI9400 and iU22 decreased with the increasing of bladder volume and had no significant difference with patient's gender (P > 0.1). CONCLUSION: BladderScan BVI9400 had the ability of high accuracy and good stability of measured data. In view of quick and conveniences, BVI9400 could be as auxiliary equipment on pelvic tumor to evaluate whether the bladder volume during fractional radiotherapy was consistency with that during CT positioning. PMID- 26665956 TI - [Application of Imaging-Guided Radiation Therapy in Pelvic Tumor Radiotherapy]. AB - OBJECTIVE: To discuss the influence of setup errors on the accuracy of pelvic cancer in IGRT, analysis setup errors and determine the CTV-to-PTV margins. METHODS: 60 pelvic cancer patients treated with Varian 23IX, all of them were performed by CBCT before and after-correction three times in the first week and after that once a week. Then, to measure the setup errors at X(left-right), Y(superior-inferior), Z(anterior-posterior) axis and E(coronal), F(sagittal), G(axial) rotation directions. RESULTS: 530 scans obtained in all, the setup errors in X, Y, Z, E, F, G were (-0.52 +/- 4.18) mm, (0.73 +/- 4.86) mm, (-0.36 +/- 3.62) mm, (0.14 +/- 1.20)degrees, (0.13 +/- 1.34)degrees, (0.21 +/- 1.73)degrees respectively and were much lower after correction at X, Y, Z axis, besides, CTV-to-PTV margins decrease a lot. CONCLUSION: The accuracy of radiotherapy can be highly increased with the use of IGRT in pelvic cancer. PMID- 26665957 TI - [Difference of CT and MRI in Diagnosis of Spinal Tuberculosis]. AB - OBJECTIVE: To investigate the imaging features and diagnostic value of MRI and CT in diagnosis of spinal tuberculosis by comparing study. METHODS: From May 2014 to December 2014, 32 patients with spinal tuberculosis were diagnosed as patients with spinal tuberculosis, and the data of MRI and CT were retrospectively analyzed. RESULTS: Patients with lesions appeared respectively in the cervical, thoracic and lumbar spine; CT diagnosis of bone destruction and vertebral disc soft tissue injury rate is lower than that of MRI, the intervertebral disc injury diagnosed rate higher than that of MRI, P < 0.05, the difference is statistically significant. CONCLUSION: CT and MRI in the diagnosis of spinal tuberculosis imaging studies are different, and combination of both can improve the diagnosis rate, can prevent and treat in a timely manner, so as to improve the treatment effect. PMID- 26665958 TI - [A Medical Devices Management Information System Supporting Full Life-Cycle Process Management]. AB - Medical equipments are essential supplies to carry out medical work. How to ensure the safety and reliability of the medical equipments in diagnosis, and reduce procurement and maintenance costs is a topic of concern to everyone. In this paper, product lifecycle management (PLM) and enterprise resource planning (ERP) are cited to establish a lifecycle management information system. Through integrative and analysis of the various stages of the relevant data in life cycle, it can ensure safety and reliability of medical equipments in the operation and provide the convincing data for meticulous management. PMID- 26665959 TI - [Application of HIS Hospital Management System in Medical Equipment]. AB - OBJECTIVE: To analyze the effect of HIS hospital management system in medical equipment. METHODS: From April 2012 to 2013 in our hospital 5 100 sets of medical equipment as the control group, another 2013 in our hospital from April 2014 may 100 sets of medical equipment as the study group, comparative analysis of two groups of medical equipment scrap rate, usage, maintenance score and the score of benefit etc. RESULTS: Control group and taken to hospital information system, his research group equipment scrap rate, there was a significant difference, the research group of equipment maintenance score and efficiency scores were higher than those of the control group (P < 0.05), the study group of equipment maintenance score and efficiency scores were higher than those of the control group. CONCLUSION: HIS hospital management system for medical equipment management has positive clinical application value, can effectively improve the use of medical equipment, it is worth to draw and promote. PMID- 26665960 TI - [Discussion on the Right of Medical Equipment Purchasing Operation Method and Effect]. AB - Medical equipment procurement authority provides sunshine supervisory channel for hospital staff by power operation monitoring software, which could operate in the open. The exercise of purchase rights should upload the content in accordance with the provisions of "internal control point". It could strengthen the procurement process control and ensure the orderly supervision links to further regulate bidding and purchasing behavior, which can prevent the exercise of uncontrolled power. PMID- 26665961 TI - This Too Shall Pass: Evidence of Coping and Fading Emotion in African Americans' Memories of Violent and Nonviolent Death. AB - Two studies examined African Americans essays on coping with violent and nonviolent death and fading affect bias. Essays from 101 African Americans were coded for psychological resolution (resolved or unresolved) and for type of death (violent or nonviolent). Linguistic analyses were used to examine the experience of loss and coping methods. Religious coping was important for nonviolent death events while social support and emotion (e.g., crying) were themes that emerged for violent death events. For unresolved violent death events, dissociation was a common theme. The perceived change in the emotional intensity of the events was examined and revealed that the negative emotion showed evidence of substantial fading. Overall, these results suggest religious coping, social support and sharing enhance coping among African American participants. These processes can help negative affect associated with death events fade, allowing for psychological resolution, healing, and resilience. PMID- 26665962 TI - A Systematic Review of the Peer-Reviewed Literature on Self-Blame, Guilt, and Shame. AB - This is the first systematic review of the evidence on the prevalence of self blame, guilt, and shame in bereaved parents. A search of PsychINFO, MEDLINE, Embase, CINAHL, PubMed, and Science Direct resulted in 18 studies for the period 1975 to 2013 which the authors have appraised. Self-blame, guilt, and shame are common in bereaved parents, albeit to varying degrees, with differential relationships to sex, and diminishing over time. There is some evidence that guilt and shame predict more intense grief reactions and that self-blame predicts posttraumatic symptomology, anxiety, and depression in bereaved parents. Heterogeneity of the studies and numerous methodological concerns limit the synthesis and strength of the evidence and the generalizability of the findings. Self-blame, guilt, and shame are commonly experienced by bereaved parents. Awareness of these affective states may assist clinicians in the identification of bereaved parents who are at a higher risk of developing adverse psychological outcomes. Overall, self-blame, guilt, and shame have received very little attention in the bereavement research, leaving many unanswered questions. Implications for practice and recommendations for future research are discussed. PMID- 26665963 TI - The Impact of Death Education on Fear of Death and Death Anxiety Among Human Services Students. AB - Human services professionals will undoubtedly work with the dying and bereaved populations at one time or other. Yet, they are poorly prepared to do so since death education, that is, lessons about the human and emotional aspects of death, its implications, and subsequent bereavement issues, is often not part of their curriculum. This nonequivalent comparison group study (N = 86) examined death fear and death anxiety among human services students before and after receiving death education using the Multidimensional Fear of Death Scale. The results showed a statistically significant decrease in death anxiety among the group of students who participated in death education compared to those who did not. PMID- 26665964 TI - Resilience and leadership for the challenges ahead. PMID- 26665965 TI - Inclusion as a core competence of professionalism in the twenty-first century. PMID- 26665966 TI - A look back. Snapshots of Hurricane Katrina, 2005. PMID- 26665967 TI - The remarkable life of Erwin Schrodinger's What Is Life? AB - In the seven decades since Schrodinger's book was published, it has gone through stages of differing appraisal, starting with guarded approbation in the 1940s. When several luminaries in molecular biology described the work as influencing their careers, the book's renown increased. In What Is Life?, Schrodinger examined genetics from the perspective of a theoretical physicist, and conjured up ideas that dilettantes admired and experts slighted. Schrodinger sowed his most important ideas in terms of metaphors, allowing readers considerable latitude for interpretation. Some found nothing worthwhile in the book, only chemical naivete and ignorance of work that had already been done. Others found deep inspiration and a desire to understand biological reproduction, even if it required new paradigms of physical science. What Is Life?--like the ancient parable of the blind men and an elephant--is an example of the ineffable nature of truth, pitting subjective experience against the totality of the reality. The legacy of What Is Life? may ultimately be respect for different opinions. PMID- 26665968 TI - Remembering World War I. An AOmegaA member goes to war--a century later, another reflects. PMID- 26665969 TI - A tale of two brains. How to rekindle the artist within. PMID- 26665970 TI - Caring for the invisible and the forgotten. PMID- 26665971 TI - Re "The academic medical center in a disrupted world". PMID- 26665972 TI - Re "The tragedy of the electronic health record". PMID- 26665973 TI - Letters to the editor. PMID- 26665974 TI - Letters to the editor. PMID- 26665975 TI - Letters to the editor. PMID- 26665976 TI - It's hard to be a real doctor now. PMID- 26665977 TI - Re "The $6 million physician: A history of robotics making surgeons better, stronger, faster". PMID- 26665978 TI - Potential of native Thai aromatic plant extracts in antiwrinkle body creams. AB - Antioxidant activities of 10 essential oils and 10 absolutes extracted from Thai aromatic plants were evaluated and compared to thyme oil, trolox, quercetin, and kaempferol by two independent assays: the 2, 2-diphenyl-1-1-picrylhydrazyl (DPPH*) radical scavenging assay and the thiobarbituric acid reactive species (TBARS) assay for lipid peroxidation. We found that four essential oils including ginger oil (Zingiber officinale Roscoe), Wan-sao-long leaf oil (Amomum uliginosum Koen), lemongrass oil (Cymbopogon citratus), holy basil oil (Ocimum sanctum L.), and the absolute of dwarf ylang-ylang [Cananga odorata Hook. f. & Thomson var. fruticosa (Craib) J. Sinclair] exhibited high antioxidant activity in both DPPH and TBARS assays and possessed satisfactory fragrance properties. These were then combined into an essential oil blend (EOB) and retested for antioxidant activity. The EOB also exhibited high antioxidant activity in the above assays. It was then incorporated into a stable cream base as EOB body cream. The EOB body cream was found to be best able under storage in stress conditions and presented significantly higher antioxidant activity than its' cream base both before and after stability testing. The effect of EOB body cream on skin surface topography was evaluated in 29 healthy volunteers using the Skin Visiometer (SV 600 FW, CK Electronic GmbH, Germany). Three parameters, Ra, Rz (roughness), and surface, were analyzed. After 4 weeks of application, the EOB body cream showed significant reductions in surface and Rz compared with before treatment (p < 0.05, paired t-test), and with untreated and placebo treatment (p < 0.05, Duncan test). These results indicate that the essential oils and absolutes from Thai plants may serve as potential sources of natural antioxidants for spa and cosmetic products designed to prevent or treat signs of skin aging. PMID- 26665979 TI - Human health risk assessment of heavy metals in cosmetics in Nigeria. AB - Forty two different cosmetics were purchased from supermarkets and cosmetic shops within Unitsha Main Market and Eke-Awka markets in Anambra, Nigeria. Of the cosmetics, 16% were locally manufactured in Nigeria while 83.33% were imported into Nigeria. The cosmetics were ashed before digestion and filtration. The filtrates were assayed for lead, cadmium, manganese, nickel, chromium, mercury, and arsenic with atomic absorption spectrophotometry at 205 A. The health risk assessment methods developed by the United States Environmental Protection Agency were employed to explore the potential human health risk of heavy metals in cosmetics. About 61.91% of the cosmetic samples contained lead with concentration in the range of 0.10-42.12 mg/kg. Cadmium levels of the cosmetics ranged from 0.01 to 1.32 mg/kg, manganese from 0.02 to 67.65 mg/kg, nickel from 0.05 to 17.34 mg/kg, chromium from 0.11 to 9.81 mg/kg, mercury from 0.003 to 0.07 mg/kg, and arsenic from 0.002 to 0.005 mg/kg. Although the target hazard quotients and the hazard indices suggest a measure of safety, cosmetics may add to the body burden of potential toxic metals after chronic exposure. PMID- 26665980 TI - The stability and controlled release of I-ascorbic acid encapsulated in poly (ethyl-2-cyanoacrylate) nanocapsules prepared by interfacial polymerization of water-in-oil microemulsions. AB - The L-ascorbic acid (AA) was encapsulated into biodegradable and biocompatible poly(ethyl-2-cyanoacrylate) (PECA) nanocapsules by interfacial polymerization of water-in-oil (W/O) microemulsions. The influences of surfactant concentration, pH value of the dispersed aqueous phase, and W/O ratio on nanocapsule size were discussed. The stability and in vitro release of encapsulated AA were also investigated. The results show that nanocapsules could be obtained under the conditions with low pH value, high fraction of aqueous phase, and appropriate surfactant concentration. The encapsulated AA was protected by nanocapsules from oxidation and presented superior storage stability in aqueous medium than pure AA. Releasing AA from the inner core of nanocapsules could be controlled by adjusting the enzyme hydrolysis extent of the PECA wall. PMID- 26665981 TI - Determination of seven sunscreen agents and two ultraviolet stabilizers in skin care products using ultra-performance liquid chromatography. AB - Ultraviolet radiation (UVR) is a well-known environmental carcinogen. Protection against UVR exposure has resulted in an increasing number of sunscreen agents being incorporated into a greater variety of cosmetic formulations including moisturizing lotions, color cosmetics, and skin care creams. Meanwhile, global regulation of sun care products is changing. New guidelines for sunscreen efficacy have resulted in a shift in product formulation that requires sunscreen products to provide broad spectrum UV protection. Since not all sunscreen ingredients protect against both UVA and UVB radiation, most sun care products require a combination of sunscreen agents. This article describes a new method for simultaneous separation and quantitation of seven organic sunscreens and two UV stabilizers using ultra-performance liquid chromatography. This method is capable of resolving all nine analytes, and has been validated for selectivity, precision, and accuracy. Because of the use of core-shell column technology, the separation is also achieved at back pressures compatible with conventional high performance liquid chromatography instrumentation. PMID- 26665982 TI - The impact of the new European Cosmetic Regulation on the preservative system. PMID- 26665983 TI - Simple Steps for Meeting the ACA's Price Transparency Requirements. PMID- 26665984 TI - What lies ahead for healthcare reform? PMID- 26665985 TI - 5 ways to better engage patients. PMID- 26665986 TI - Risk-adjusted base payments can support the move to value. AB - Value-based care delivery and payment continue to penetrate the marketplace, redefining the roles primary care physicians are expected to play. Risk-adjusted base payments can help ensure that these physicians receive stable, predictable monthly or quarterly payments for the added responsibilities they will take on managing the health of populations through accountable care organizations, patient- centered medical homes, and other value-based organizations. As payerand provider incentives become aligned in value-based care delivery, payment arrangements should be designed to reflect that alignment. PMID- 26665987 TI - Helping value-based care delivery pay for itself. AB - The following steps helped a Virginia medical group generate additional fee-for service revenue through its population health management infrastructure: Building patient-centered medical homes structured around care teams Using registries and automated messaging to generate office visits that engage patients and address gaps in care Enabling care managers to manage post-discharge visits, which are compensated at higher levels by Medicare, and annual wellness visits Capitalizing on health plan incentives for quality and care coordination PMID- 26665988 TI - Succeeding in a disruptive healthcare environment. AB - A greater level of consumerism in health care is leading to market dislocations that involve the shift of services to outpatient settings and to web-based and mobile modes of care. Hospitals and health systems risk losing market share and clinical and financial viability if they do not adjust their business models to account for these changes. When planning for such a transformation, organizations should commit to a new view of health care, invest in consumer-centric outpatient and virtual strategies, use new metrics to gauge success, and create a blueprint as a guide. PMID- 26665989 TI - Integrating the revenue cycle for improved health system performance. AB - Three integrated revenue cycle models reflect the various levels of integration a health system'might find desirable or feasible based on its current circumstances and environment: Model A: A single health system executive provides oversight, but physician and hospital revenue cycles are managed separately. Model B: A single health system leader provides oversight, with a functional framework for management at the director level. Model C: Integration is complete for all processes. PMID- 26665990 TI - Organizing for the 'second curve': combining health plans and provider systems. AB - Provider systems should ask four questions as they seek to incorporate health plans. Is the health plan on track to build critical mass quickly enough? Does the plan balance provider and health plan business priorities? Is the provider system willing to let its health plan compete freely in the market? Is the provider system's overall vision understood and backed internally? PMID- 26665991 TI - The true financial impact of hospital readmissions. AB - Hospital executives working to reduce the cost of readmissions should note that: The penalty imposed by the Centers for Medicare & Medicaid Services (CMS) for excess readmissions can be disproportionately high The true cost of readmissions goes beyond the CMS penalty Even small reductions in readmissions can substantially reduce penalties Changes to healthcare reimbursement, such as bundled payments, will also incentivize hospitals to reduce readmissions. PMID- 26665992 TI - Just how much value can we create? PMID- 26665993 TI - Paving the road to success under value-based payment models. PMID- 26665994 TI - The value of variable rates in a world of low rates. PMID- 26665995 TI - Readmission rates by type of facility. PMID- 26665996 TI - It's time we get EHR on a truly "meaningful" track. PMID- 26665997 TI - Highlights from MAG summer legislative seminar. PMID- 26665998 TI - Imagine that ... and more. PMID- 26665999 TI - Telemedicine: Transforming Georgia's landscape. PMID- 26666000 TI - New rules for administration of vaccines under protocol. PMID- 26666001 TI - An update on the MAG Foundation. PMID- 26666002 TI - How to comply with the Anti-Kickback Statute. PMID- 26666003 TI - Georgia survey highlights physicians' ethical and professional concerns. PMID- 26666004 TI - Medical practice embezzlement. PMID- 26666005 TI - EHR Meaningful Use Stage 3: Greater flexibility, but heightened requirements. PMID- 26666006 TI - CMS issues proposed 2016 Medicare physician fee schedule. PMID- 26666008 TI - Life lessons: continued. PMID- 26666007 TI - Alarm or white noise? PMID- 26666009 TI - [Review on requirements of drug allergy or pseudoallergic reactions in pre clinical evaluation]. AB - Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug, drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years, FDA, SFDA OECD, ICH and WHO have published several guidelines on per clinical immunotoxicity evaluation, however, no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation. PMID- 26666010 TI - [Toxicogenomics and its application in safety evaluation of traditional Chinese medicine]. AB - Toxicogenomics (TGx) refers to a set of technologies that assess genome-wide responses after toxic agent exposure. Altered gene expression patterns that are caused by specific exposures reveal how toxicants may disrupt cellular processes and lead to side effects. Development and application of " omics" technology facilitate the toxicogenomic research which sharing and interpretation of the enormous amount of biological information generated in toxicologic field. In recent years TGx has been widely valued and successfully applied as an effective research tool to evaluate the toxic effects of traditional Chinese medicine (TCM). Here we reviewed current progress in the field of TGx and focused on its application in traditional Chinese medicine safety evaluation, especially in revealing the mechanism, finding potential toxic biomarkers and studying compatibility detoxification of TCM. PMID- 26666011 TI - [Genotoxicity research thought and method on traditional Chinese medicine]. AB - Genotoxicity research takes an important place in traditional Chinese medicine safety evaluation. Genotoxicity test on traditional Chinese medicine has been paid great attention since 1970s. Currently, the most developed genotoxicity test methods included: bacterial reverse mutation test and mouse lymphoma assay which are used to detect relevant genetic changes, micronucleus test and chromosomal analysis which are used to measure chromosomal aberration, and single cell electrophoresis assay which is used to test DNA damage. This article reviews research progress on genotoxicity of traditional Chinese medicine, evaluation methods of genotoxicity, the problems and solutions on genotoxicity evaluation of traditional Chinese medicine, and new technique used in genotoxicity test. PMID- 26666012 TI - [Genetic polymorphism of FMO3 and its role in drug metabolism and toxicity]. AB - The flavin-containing monooxygenase 3 (FMO3) is an important hepatic microsomal enzyme. Numerous mutations of FMO3 gene have been reported, and polymorphic varients of the gene have been identified. Several studies indicated that variability in the expression of FMO3 involved in some nitrogen, or sulfur containing durg metabolism. This review summarizes the genetic polymorphism of FMO3 and its role in drug metabolism and toxicity. PMID- 26666013 TI - [Risk assessment for clinical external application of calomel]. AB - Calomel is a common traditional Chinese medicine (TCM) containing mercury in clinical external application. Although the toxicity of calomel has attracted concern, there is no unified standard yet in clinical external application. Risk assessment is used for evaluating the potential health effects of hazardous substances. The purpose of this article was to evaluate the health risk of calomel in clinical external application on the basis of toxicity data, to ensure safe and rational application of TCM containing calomel. The toxicity data of transdermal administration of calomel or mercurous chloride were collected by searching the literature. The daily maximum exposure dosage of calomel in clinical external application was estimated by following the four procedures of risk assessment, and Margin of Safety (MOS) as an evaluation indicator was then calculated to evaluate the safety of calomel on clinical application. It has been reported that the adult in single transdermal administration of calomel at 1. 5 g was lethal. Based on the LOAEL of calomel for long-term transdermal exposure (1 month) in rats was 0.096 g . kg(-1) . d(-1), the NOAEL of calomel for patients (about 60 kg) by external application within 2 weeks was estimated to be 1.46 mg . kg(-1) . d(-1). When MOS value equals to 1, the daily maximum exposure of calomel in clinical external application within 2 weeks was calculated to be 1.1 g. The results suggest that daily single dose of calomel in clinical external application should be lower than 1.5 g for adults, and more attention should be paid to changes in hepatic and renal function of patients when repeated dose more than 1.1 g within 2 weeks. The approach of risk assessment could be helpful in rational application of TCM containing mercury. PMID- 26666014 TI - [Evaluation and study of pseudo-allergic reactions of three kinds of traditional Chinese medicine injections and its mechanisms]. AB - To evaluated the pseudo-allergic reactions of cordate houttuynia, pulse activating and Qingkailing injection in mice, the ICR mouse were divided into different test groups, then were intravenously injected with three traditional Chinese medicine injections, positive control compound 48/80 and physiological saline as normal control. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. At the same time, the mechanisms of the traditional Chinese injections' pseudo-allergic reactions was studyed. ICR mice were injected with the test substances as above without EB, blood in a part of mice were collected after 5 min, and the level of histamine in the plasma were measured. Blood in the other part of mice were collected after 30 min, and the level of VEGF, TNF-alpha and IL-10 in the serum were measured. The reasults showed that except the cordate houttuynia injection, pulse-activating injection in 1. 5 times clinical concentration and Qingkailing injection in 3.3 times clinical concentration caused mild pseudo-allergic reactions mainly for vascular permeability, no pseudo allergic reactions occurred when the concentration of the two injections was below the concentration metioned above; 5 minutes after intravenous injection of the three TCM injections into ICR mice with the highest dose, the levels of histamine in plasma of pulse-activating injection and Qingkailing injection groups were increased significantly, 30 minutes later, the levels of VEGF, TNF alpha and IL-10 in the serum of all groups were no significant change compared to normal group. The mouse of pulse-activating and Qingkailing injection groups showed inflammatory changes in ear and lung tissues. It can be conluded that when the dose or concentration increased to a certain extent, pulse-activating and Qingkailing injection could induce pseudo-allergic reactions on ICR mice, the increased histamine realease maybe the main reason for pseudo-allergic reactions of the two traditional Chinese medicine injections. In addition the author preliminary thought that inflammatory mechanisms leading to hyperpermeabilities were the main reason of the traditional Chinese medicine injection's pseudo allergic reaction. PMID- 26666015 TI - [Preclinical evaluation of pseudoallergic reactions on Chinese herbal injections: study on animal strain and gender difference]. AB - Pseudoallergic reactions occured after the first administration of patients, and the pathogenic mechanisms of them were different from the allergic reactions which needed excitation after antigen sensitization. To provide a basis for evaluation, clinical use and drug development of pseudoallergic reactions, the models were established by two kinds of Chinese herbal injections (CHI) both on different strain or gender mice. With the use of ICR, Kunming, BALB/C, C57 mice, pseudoallergic tests of two CHI were conducted to compare the sensitivity of four strains mice, and compared the differences in male and female animals. Test substances contain 0.8% Evans blue (EB) were intravenously injected into different strain and gender mice. Scores of ear blue staining and quantitation of ear EB exudation were the parameters for pseudoallergic reaction. Results of strain difference indicated that both CHI A and B could cause severe pseudoallergic reactions indicated by obvious vascular hyperpermeability on ICR mice. The pseudoallergic reactions in ICR mice are more obvious under the the same dose of injection, which stated the sensibility of ICR mice. And the reactions of KM mice and BALB/C mice were slightly reduced which compared to ICR mice, even alomost nothing on C57 mice. Comparison results of gender difference showed that one CHI was not have significant difference in male and female animals, but male animals were more susceptible than females on another CHI. Therefore, ICR mice were preferable experimental strain on the model of pseudoallergic reactions induced by CHI A and B. Because of female animals were easily influenced by estrous cycle, the pseudoallergic reactions induced by CHI A and B select and use male mice befittingly. PMID- 26666016 TI - [Influence of solvent and drug preparation time on Shuanghuanglian injections induce pseudo-allergic reaction]. AB - Choosing the right solvent and timely use is the basis of rational drug use and the most direct and efficient way to improve the safety of traditional Chinese medicine injections. This study aimed to evaluate the influence of solvent and drug preparation time on Shuanghuanglian injection inducing pseudo-allergic reactions with mouse mode. The two tests were carried out: (1) Comparative experiment between different solvent: Shuanghuanglian injection preparation to the appropriate concentration with 0.9% sodium chloride injection and 5% dextrose injection, mixed with Evans blue, at one time intravenous injected into mice, 30 minutes later, the mouse ears vascular permeability were observed and compared. (2) Comparative experiment among different preparation time: placed 10 min, 2.5 h, 6 h and 24 h after Shuanghuanglian injection were prepared and then to detect the pseudo-allergic reactions in mice using the same methods as in (1). The results showed that there was no significant difference in the pseudo-allergic reactions in mice which induced by the same dose of Shuanghuanglian injection, respectively with 0.9% sodium chloride injection and 5% dextrose injection preparation, and with the extension of preparation time, the degree of pseudo allergic reactions of Shuanghuanglian injection was gradually severe. PMID- 26666017 TI - [Study of screening pseudoallergenic substances of Shuanghuanglian injection]. AB - In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections. PMID- 26666018 TI - [Material for evaluation of notoginseng total saponin preparation induced pseudoanaphylactoid reactions]. AB - The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF alpha levels in notoginseng total saponin preparation middle-dose group and high dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-alpha, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree. PMID- 26666019 TI - [Effects of Reduning injection on activity of hepatic microsomal CYP450 isozymes in rats]. AB - To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects. PMID- 26666020 TI - [Cardiotoxicity study of Shenfu compatibility in rats based on metabonomics]. AB - To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g . kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity. PMID- 26666021 TI - [Preliminary study on hepatotoxicity induced by dioscin and its possible mechanism]. AB - Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 umol . L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 umol . L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A. PMID- 26666022 TI - [Study on efficacy accompanied by side effects of water extraction components of Evodiae Fructus based on syndrome model]. AB - The range of effective dose and mechanism of abirritation about water extraction components of Evodiae Fructus on the stomach cold syndrome model in mice were preliminary studied. The method of stomach cold-syndrome model in mice was built, which were administrated with different doses water extraction components of Evodiae Fructus, observing abirritation and toxicity by the classical hot plate method, detecting the level of ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR in serum and ALT, AST in hepatic tissue, and recording toxicity symptoms in mice according to the list of relevant toxicity reaction. The water extraction component of Evodiae Fructus has obvious analgesic action after administration 30 min, arriving peak effect after administration 60 min, showing certain "dose-time toxicity" relationship. ALT and AST levels in mice serum and liver tissue enhanced; PGE2, MDA, NO, NOS enhanced in mice serum; SOD, GSH, GSH-Px reduced; the BUN, CR levels was no significant alteration; liver weight/ body weight enhanced; kidney weight/body weight was no significant alteration. The a irritation mechanism of volatile oil of Evodiae Fructus was connected with suppressing pain transmitters release, per oxidative damage mechanism and NO damage, which also induced hepatotoxicity and the mechanism of hepatotoxicity is main lyoxidative damage, showing certain "dose-time-toxicity" relationship in accordance to hepato-toxicity injury. PMID- 26666023 TI - [Assessment of efficacy-toxicity-syndrome correlation based on anti-inflammation of Sophorae Tonkinensis Radix et Rhizoma in excess-heat mice]. AB - Models of throat excess-heat mice were established and different dosages of water extract of STRR were ig given to mice to observe anti-inflammatory effect and its mechanism. The activities of ALT, AST and the contents of TNF-alpha, T3, rT3, T4, SOD, MDA, PEG2, NO, NOS, Cr, BUN, GSH and GSH-Px in serum were tested while liver index, kidney index, spleen index and thymus index were measured. The anti inflammatory efficacy accompanied by side effects and mechanisms of water extract of Sophorae Tonkinensis Radix et Rhizoma (STRR) in excess-heat mice were investigated to clear safety dose-dependence range and the relationship of efficacy, toxicity and syndrome. In the experiment, water extract of STRR showed a strong inhibitory effect on ear edema by croton oil in throat excess-heat mice. The activities of ALT, AST in serum and liver index were all higher than that of normal group after multiple administration. PEG2, SOD, MDA, NO, NOS, GSH and GSH Px had obvious changes. According to the results, water extract of STRR has an anti-inflammatory effect on acute inflammation in throat excess-heat mice and it is stronger than that in normal mice. The anti-inflammatory effect of STRR is related to the reduction of inflammatory mediators release. Side effects and hepatotoxicity will be produced on clinical efficacy dosage. The mechanisms of anti-inflammation and hepatotoxicity are all in connection with oxidative damnification. PMID- 26666024 TI - [Advance and prospect in studies on anaphylactoid reaction of traditional Chinese medicine injections]. AB - Because of the rapid action and high bioavailability, traditional Chinese medicine injections (TCMIs) had been widely used in clinical critical field. In recent years, with the increasing reports of clinical adverse reaction, more and more attention was paid to them, and acute allergic reaction was the main adverse reaction. Acute allergic reaction included type-I anaphylaxis reaction and anaphylactoid reaction, the latter had been found in a variety of TCMIs and accounted for 77% of adverse reaction. But the mechanism of anaphylactoid reaction was not completely understood, the standard animal model for TCMIs was not established, and the technical guidance for anaphylactoid reaction was not formulated. Thus the three aspects included mechanism, evaluation index and evaluation methods of TCMIs for anaphylactoid were reviewed. Five ways including direct stimulating pathway, complement pathway, coagulation pathway, kallikrein kinin pathway and acute allergic pathway were the main mechanism of anaphylactoid reaction; whole animal model and cell model were the main evaluation methods; the occurrence index and effect index were reviewed for the evaluation index analysis. PMID- 26666025 TI - [Real-time detection of quality of Chinese materia medica: strategy of NIR model evaluation]. AB - The definition of critical quality attributes of Chinese materia medica ( CMM) was put forward based on the top-level design concept. Nowadays, coupled with the development of rapid analytical science, rapid assessment of critical quality attributes of CMM was firstly carried out, which was the secondary discipline branch of CMM. Taking near infrared (NIR) spectroscopy as an example, which is a rapid analytical technology in pharmaceutical process over the past decade, systematic review is the chemometric parameters in NIR model evaluation. According to the characteristics of complexity of CMM and trace components analysis, a multi-source information fusion strategy of NIR model was developed for assessment of critical quality attributes of CMM. The strategy has provided guideline for NIR reliable analysis in critical quality attributes of CMM. PMID- 26666026 TI - [Application of ultrasound counter currentextraction in patent of traditional Chinese medicine]. AB - The patent information of ultrasound countercurrent extraction used in traditional Chinese medicine was analyzed in this paper by the samples from Derwent World Patent Database (DWPI) and the Chinese Patent Abstracts Database (CNABS). The application of ultrasound countercurrent was discussed with the patent applicant,the amount of the annual distribution, and the pharmaceutical raw materials and other aspects. While the technical parameters published in the patent was deeply analyzed, such as material crushing, extraction solvent, extraction time and temperature, extraction equipment and ultrasonic frequency. Thought above research, various technical parameters of ultrasound countercurrent extraction used in traditional Chinese was summarize. The analysis conclusion of the paper can be used in discovering the technical advantages, optimizing extraction conditions, and providing a reference to extraction technological innovation of traditional Chinese medicine. PMID- 26666027 TI - [Anti-feeding activity of total ginsenoside from Panax ginseng to 4th-instar Mythimna separata larvae]. AB - This paper is in order to study the anti-feeding and growth inhibition activity of toatal ginsenoside of ginseng stems and leaves against 4th-instar Mythimna separata larvae. Simulating natural growing condition indoors, on the base, To study the anti-feeding and growth inhibition activity of toatal ginsenoside against 4th-instar M. separata larvae by leaf disc test. The toatal ginsenoside appeared to be of significant antifeeding activity against 4th-instar M. separata larvae. The 4th-instar M. separata larvae fed on the leaves of Sorghum bicolor treated with 20, 10, 5 g . L(-1) toatal ginsenoside. At 8 h, non-selective anti feeding rate were 88.67%, 64.40% and 47.36%, and selective anti-feeding rate were 62.49% , 44.29% and 34.19%; Compared with the photographic, The toatal ginsenoside conld make the development period had prolonged 13h in treated group. The toatal ginsenoside had significant inhibition effect on feeding and growth and development against 4th-instar M. separata larvae, and inhibition effect increases as the increase of concentration ginsenoside. PMID- 26666028 TI - [Habitat suitability assessment of medicinal Polyporus umbellatusin China based on Maxent modeling]. AB - Geographic distribution of Polyporus umbellatus was predicted by using distribution records. Based on 42 distribution records from 12 provinces and bioclimatic data (1950-2000), georaphic distribution of P. umbellatus was modeled using Maxent. The results showed thatthe Receiver Operating Characteristic (ROC) curve analysis method was used to assess the accuracy of MAXENT model and the area under ROC curve (AUC) value of MAXENT was 0. 960 which suggested that the result of assessment was dependable. The geographic distribution pattern of were divided into three distribution block based on distribution values of 0.5-0.8: small area of Heilongjiang, Jilin, Liaoning and Hebei province, the board area of Yunnan, Guizhou and Sichuan, the southeast area of Tibet and the most area of Shanxi and Shannxi, the southeast board area of Shannxi, Gansu and Ningxia. Jackknife Test showed that average precipitation in warm seasons had the greatest contribution to the distribution gain of P. umbellatus, followed by mean temperature of driest quarter and annual mean temperature. The object suggests the potential distribution areasof P. umbellatus which is useful for the habitat conservation and introduction of P. umbellatus. PMID- 26666029 TI - [Studies on digestive enzyme activity of Whitmania pigra in different months old]. AB - Studies on the variation of amylase, lipase and lrotease activity of Whitmania pigra in 0-6 months old using 3, 5-dinitro- salicylic acid colorimetry, right nitrophenyl palmitate ester (rho-NPP) colorimetry and folin-phenol method. The results showed that pro- tease activity remained low before 1.5 months old and with the highest activity in 2 months old, but after showing a small peak in 4 months, alkaline protease rapid declined. Amylase was low at born, then gradually increased the activity of the highest in 2.5 months old. Lipase with a strong vitality at birth, then 1 month with minimum and 2 months peaked, but appeared a small peak in 4 months old. In summary, only lipase exhibits strong activity at birth, lipase with the strongest activity in the digestive tract during develop- ment. Protease, lipase and amylase with the strongest activity at 2-3 months old, but were decreased after 4 months old. PMID- 26666030 TI - [Correlation analysis between foliar endophytic fungi of Salvia miltiorrhiza and effective components]. AB - The aim of this study was to comprehensively investigate the correlations between foliar fungal endophyte communities and effective components accumulations in Salvia miltiorrhiza. Foliar samples of S. miltiorrhiza were collected in 5 different areas. Their fungal endophyte communities and effective component contents were determined by denaturing gradient gel electrophoresis (DGGE) and high performance liquid chromatography (HPLC), respectively. The results showed that, for characteristics of foliar fungal endophyte communities and effective component contents, there were both similarities and differences among the five samples. Correlation analysis of DGGEs' band and 24 effective components revealed a significant correlations (P < 0.01). For examples, 4 bands (15, 18, 23 and 26) were all significantly correlated with the accumulations of caffeic acid, salvianolic acid B, salvianolic acid C and dihydrotanshinone I. PMID- 26666031 TI - [Cloning and expression analysis of transcription factor gene DoWRKY1 in Dendrobium officinale]. AB - WRKY transcription factors are novel transcriptional regulatory factors, which play an important role in regulating plant development, metabolism and other physiological processes. In this study, a new Dendrobium officinale WRKY transcription factor, designated as DoWRKY1 was cloned by using RT-PCR and RACE (GenBank Accession No. KF953910). Bioinformatic analysis demonstrated that, the full-length cDNA of DoWRKY1 was 1,704 bp. And DoWRKY1 contained a 1,629 bp open reading frame (ORF) that encoding a peptide of 542 amino acid residues. The putative DoWRKY1 protein contained two conserved WRKY domains and it belonged to the group I WRKY family protein. Yeast one-hybrid experiment showed that DoWRKY1 had transcriptional activation ability in yeast, and it could activate the expression of downstream report genes (His3 and Ade2). Semi-quantitative RT-PCR experiment showed that DoWRKY1 expressed in roots, stems, leaves and protocorm like bodies. Real-time qRT-PCR proved that DoWRKY1 could be induced by methyl jasmonate (MeJA) and chitosan (Chitosan), and the expression level of this gene can reach the expression peak at 2 h and 1 h, respectively. These results are useful for further determination of the regulation function of this gene in secondary metabolism of D. officinale. PMID- 26666032 TI - [Analysis of fatty composition from different parts of Ganoderma lucidum]. AB - The oil content and fatty acid composition of Ganoderma lucidum collected from different producing areas, varieties, tissue types and growth periods were measured and analyzed. The results showed that the oil content was 23. 61%-34.17% in different domestic producing areas of China; the oil content of fruiting bodies from major varieties cultured in Zhejiang province were 0.81%-1.87%, wall unbroken spores were 0.07%-0.24%, wall-broken spores were 27.54%-34.17%, so the oil content of wall-unbroken spores were much higher than fruiting bodies, and wall-breaking treatment would increase the oil extraction rate 150-340 times. G. lucidum spores oil was mainly composed of unsaturated fatty acid composition. oleic acid and linoleic content were 53.26%-58.16% and 10.69%-16.87% respectively. Fatty acid composition ratio of spores and fruiting bodies were significantly different by PLS-DA. Determining the composition of fatty acid, especially the content of oleic acid, stearic acid and palmitic acid, could identify the tissue types of G. lucidum products' sources. In addition, the study result showed that the spores and fruiting bodies collected in the first year contained richer oil and fatty acid than second year's samples from the same variety of G. lucidum. PMID- 26666033 TI - [Studies on macroscopic and microscopic characteristics of Ophiocordyceps xuefengensis]. AB - The macroscopic characteristics, tissue, caterpillar body wall and powder of Ophiocordyceps xuefengensis in different batch numbers were observed and researched by the macroscopic and microscopic identification methods. The result shows that the morphology, size, abdominal annulations of caterpillar, etc. of 0. xuefengensis are the macroscopic identification characteristics, the caterpillar body surface mycelium, body wall sculpture and crochets on abdominal legs are the microscopic identification characteristics. These characters are stable and regular discriminant features, which are proved to be the identification basis of O. xuefengensis. In addition, The characters such as crochets on abdominal legs arrange in two parallel ellipse rings, the inner crochets are long strip, and the external toes are unciform, are specific. PMID- 26666034 TI - [Nasal submicron emulsion of Scutellariae Radix extract preparation technology research based on phase transfer of solute technology]. AB - Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable. PMID- 26666035 TI - [Determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials by LC-MS/MS]. AB - To develop a LC-MS/MS method for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials, the column was Agilent ZORBAX Eclipse plus C18 (3.0 mm x 50 mm, 1.8 um), and the mobile phase consisted of methanol-water (containing 0.2% formic acid) (95:5) at a flow rate of 0.5 mL . min(-1). The multiple reaction ion monitoring (MRM) with an ESI interface in the negative ion mode was selected. The results showed that the linear ranges of five kinds of ginkgolic acids were in the range of 0.2-36.0 ug . L(-1) (r >= 0.999 5). The lowest limit of quantification (LOQ) of ginkgo acid C13: 0, C15:1, C17:2, C15:0 and C17:1 were 0.18, 0.18, 0.21, 0.10 and 0.20 ug . L(-1), respectively. The average recovery was between 73.28% and 87.56%, and the average content of total ginkgolic acids in three batches of samples was in the range of 0.023-0.028 ug . g(-1), which was much lower than 2 ug . g(-1) prescribed in drug registration standards. This method is simple and rapid with high sensitivity, which can be used for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials. PMID- 26666036 TI - [Study on effective substance basis and molecular mechanism of Qigui Tongfeng tablet using network pharmacology method]. AB - Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application. PMID- 26666037 TI - A new dimeric lignan from Zanthoxylum simulans. AB - To study the chemical constituents from Zanthoxylum simulans and their anti inflammatory activity. The constituents of Z. simulans were isolated and purified using various column chromatographies. Their chemical structures were elucidated using extensive spectroscopic methods. The compounds were assayed inhibitory activity against NO production in LPS stimulated RAW 264.7 cells. Four compounds were obtained from the ethanol extract of Z. simulans and determined to be isozanthpodocarpin B(1), kobusin (2), (+)-fargesin (3), and epieudesmin (4). Compound 1 exhibited NO production inhibitory effect with IC50 value of 14.49 umol . L(-1). Compound 1 is a new dimeric lignan and may be serve as potential anti-inflammatory agent in the future. PMID- 26666038 TI - [Saponins from roots of Securidaca inappendiculata with cytotoxic activities]. AB - Seven acylated triterpene saponins were isolated from the roots of Securidaca inappendiculata by means of various chromatographic techniques such as silica gel, MPLC, preparative HPLC, and semi-preparative HPLC. Their chemical structures were identified as securioside A(1), securioside B(2), 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2) [beta-D-glucopyranosyl-(1-->3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-beta-D fucopyranosyl ester(3), 3-O-beta-D-glucopyranosyl presenegenin 28-O-beta-D xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1- >3) ] -4-O-[(E/Z)-3, 4-dimethoxycinnamoyl]-beta-D-fucopyranosyl ester(3/4), 3-O beta-D-glucopyranosyl presenegenin 28-O-alpha-L-arabinopyranosyl-(1-->3)-beta-D xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-4-O-[(E)-3,4 dimethoxycinnamoyl]-beta-D-fucopyranosyl ester(5), polygalasa- ponin XLV(6), and polygalasaponin XLVI (7) on the basis of spectroscopic data analysis and physicochemical properties. Among them, compounds 5-7 were isolated from the plants in genus Securidaca for the first time and compounds 3, 3/4 were isolated from the species for the first time. The cytotoxicity assay showed that compounds 2, 3/4, 5 have moderate cytotoxic activities against Lewis lung carcinoma LLC cells with IC50 values of 41.10, 38.17, and 48.92 umol . L(-1), respectively; compound 2 exhibited moderate cytotoxic activities against human breast cancer MCF-7 cells with an IC50 value of 47.93 umol . L(-1). PMID- 26666039 TI - [Study on HPLC specific chromatograms of Lu Dangshen]. AB - In this paper, the RP-HPLC specific chromatography was adopted, with DIKMA-C18 (4.6 mm x 250 mm, 5 um) as the chromatographic column, with a gradient elution compose of acetonitrile and 0.1% phosphoric acid at flow rate of 0.8 mL . min( 1), the detection wavelength was 220 nm. The difference of the HPLC specific chromatograms between the Lu Dangshen and other different base sources and different producing area of Codonopsis Radix was compared, involved in the similarities and differences of the number and the relative peak area of characteristic peaks in the HPLC specific chromatograms. The HPLC specific chromatograms of Lu Dangshen was established and the relative retention times of seven peaks was determined, and the peaks of codonopyrrolidium B, syringin, lobetyolin, tangshenoside I and atractylenoide III were identified; The HPLC specific chromatograms of Lu Dangshen provided a method for scientific evaluation and effective control the quality of Lu Dangshen from Shanxi famous-region. PMID- 26666040 TI - [Establishment of different origin Peganum harmala qualitative discrimination model based on near-infrared spectroscopy]. AB - The optic-fiber sensor technology combined with near-infrared diffuse reflection spectroscopy was applied to directly analyze Peganum harmala and identify different origin of P. harmala on the basis of principal component analysis, clustering analysis, SIMCA method, which resulted in the establishment of a new method to rapidly and nondestructively identify the origin of P. harmala. The original full wavelength spectrum for principal component analysis and the score of first two principal components can distinguish four origins of P. harmala basically. In the wavelength range of 866-2,507 nm, MSC as pretreatment method to establish the best model of clustering analysis to forecast the samples with the accuracy of 91.67%, can distinguish the four origins of P. harmala while in the wavelength of 1,085-2,507 nm, normalization method as pretreatment methods to establish a best model of SIMCA to forecast the sample, all the samples except for the changji sample have been identified with a total recognition rate of 97.22%. The results show that using near infrared diffuse reflectance spectroscopy combined with SIMCA is the best method that can be effectively used to identify the P. harmala. PMID- 26666041 TI - [Protective effect of asiatic acid from Potentilla chinensis on alcohol hepatic injury in rats]. AB - To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg . kg(-1) AA), the model group (5.0-9.0 g . kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg . kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-alpha, IL-1beta, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-kappaB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-alpha, IL-1beta, TLR4, CD14, MyD88 and NF kappaB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-kappaB inactivation and the reduction of inflammatory response. PMID- 26666042 TI - [Effect of paeoniflorin on oxidative stress and energy metabolism in mice with lipopolysaccharide (LPS)-induced brain injury]. AB - Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg . kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg . kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+) K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism. PMID- 26666043 TI - [Rat intestine absorption kinetics study on cucurbitacin B-sodium deoxycholate/phospholipid mixed nanomicelles with in vitro everted gut sacs model]. AB - To investigate the absorption kinetics of Cu B-SDC/PLC-MMs in rat different intestinal segments and compared with the absorption of Cu B suspension. The in vitro everted gut sacs model was established to study the absorption characteristics of Cu B-SDC/ PLC-MMs in rat duodenum, jejunum, ileum and colon, and the content of cucurbitacin B was detected by HPLC method, and the effects of concentrations on intestinal absorption were evaluated as well. The results showed that the absorption of Cu B-SDC/PLC-MMs was linearity at different intestine segment and different concentrations (R2 > 0.9), which was consistent with zero order rate process. The Ka of different intestine segments showed a concentration-dependent increasing along with the raised concentration of Cu B SDC/ PLC-MMs, indicating that it was likely to be a mechanism of passive absorption. The best absorption site of Cu B-SDC/PLC-MMs was ileum, and its absorptions in different intestinal segments were superior to cucurbitacin B suspension. SDC/PLC-MMs could significantly enhance the intestinal absorption of cucurbitacin B, and the study of intestinal absorption kinetics of Cu B-SDC/PLC MMs had gave a support to its further reasonable solidfication. PMID- 26666044 TI - [Absolute bioavailability of ginkgolide compounds in rats]. AB - To investigate the pharmacokinetic characteristics and absolute bioavailability of ginkgolide A (GA), ginkgolide B (GB) and bilobalide (BB) in rats. In this experiment, a high-performance liquid chromatography-tandem mass spectrometry (LC MS/ MS) method was established to determine the plasma concentrations of GA, GB and BB in rats after rats were administrated with the three drugs through ig and iv respectively. The main pharmacokinetic parameters and absolute bioavailability of three ginkgolide compounds were obtained by using pharmacokinetic software DAS 2. 0. After the inject of GA, GB and BB, the results showed Cmax at (513.9 +/- 116.9), (701.3 +/- 76.0), (5,255.6 +/- 476.8) ug . L(-1) and AUC0.24h of (960.9 +/- 268.5), (779.5 +/- 140.6), (7,409.3 +/- 1,181.1) ug . h . L(-1), respectively; after the oral administration, the results showed Cmax at (522.9 +/ 39.9), (146.8 +/- 31.6), (2,711.9 +/- 588.9) ug . L(-1) and AUC0-24 h of (1,760.4 +/- 300.7), (636.6 +/- 180.3), (16,651.4 +/- 1,306.5) ug . h . L(-1), respectively. The absolute bioavailability of GA, GB and BB in rats was (61.1 +/- 10.4)%, (27.2 +/- 7.7)%, (56.2 +/- 4.4)%, respectively. The method established in this experiment has a good specificity and sensitivity and so can be used to study the pharmacokinetics and absolute bioavailability of GA, GB and BB in rats. PMID- 26666045 TI - [Contrasted study on pharmacokinetics of Tibetan medicine Renqing Mangjue compatible with Zuota]. AB - To provide insights into the mechanism for the attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue, a contrasted study was carried out on the pharmacokinetics of brucine and strychnine in mice plasm, which are active and toxicant ingredient in the Tibetan medicine Renqing Mangjue. LC-MS/MS was used to detect simultaneously the concentrations of brucine and strychnine in mice plasm at-different time intervals after administration parallelly and randomly, and the pharmacokinetic software Kinetica 5. 0 was selected to non compartmental analysis (NCA) for data, and statistical analysis software SPSS 19. 0 was used for significance test on the pharmacokinetic parameters. A reliable LC MS/MS method was established for the determination of brucine and strychnine in blood plasma, which are consistent with the requirements of the preclinical pharmacokinetic study confirmed by the methodology. The linear concentration ranges of brucine and strychnine were 0.301-104.4 ug . L(-1) (r = 0.999 5) and 0.305-106 ug . L(-1) (r = 0.999 7), respectively; The intra-day and inter-day variable coefficients were both less than 10.0% with good precision; The average extraction recoveries of brucine and strychnine were 116.23% and 112.82%, and RSD were 3.2% and 2.3% separately;The average matrix effects of brucine and strychnine were 122.48% and 116.36%, and RSD were 7.7% and 4.4%, respectively. The pharmacokinetic results showed that AUCtot of brucine and strychnine in Zuota group were both increased remarkably (P < 0.05), and the Cmax of brucine in Zuota group was about 5.25-fold higher than that of brucine in non-Zuota group (P < 0.05). The Tmax of brucine and strychnine reduced to one-eighth and one-quarter respectively compared with those in Non-Zuota group. In addition, the eliminations of brucine and strychnine in vivo were accelerated after the compatibility of Zuota. A significant difference (P < 0.05) occurred at the MRT0 t, of brucine, while the MRT0-infinity and Lz of strychnine were statistically significant upon the inspection level alpha = 0.1. It was found that the absorption degree of brucine and strychnine in Zuota group increased in the range of the safe dose (or concentration), while their elimination rates were accelerated, which may be one of the mechanisms for attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue. PMID- 26666046 TI - [Preliminary processing, processing and usage of Dendrobii Caulis in history]. AB - On account of the dense cuticles of the fresh stem and the light, hard and pliable texture of the dried stem, Dendrobii Caulis is difficult to dry or pulverize. So, it is very important to the ancient doctors that Dendrobii Caulis should be properly treated and applied to keep or evoke its medicinal effects. The current textual research results about the preliminary processing, processing and usage methods of Dendrobii Caulis showed that: (1) In history the clinical use of fresh or processed Dendrobii Caulis as teas and tinctures were very common. (2) Its roots and rhizomes would be removed before using. (3) Some ancillary approaches were applied to shorten drying times, such as rinsing with boiling mulberry-ash soup, washing or soaking with liquor, mixing with rice pulp and then basking, etc. (4) According to the ancients knowledge, the sufficient pulverization, by means of slicing, rasping, hitting or pestling techniques, was necessary for Dendrobii Caulis to take its effects. (5) The heat processing methods for Dendrobii Caulis included stir-baking, stir-frying, steaming, decocting and stewing techniques, usually with liquor as an auxiliary material. Among above mentioned, steaming by pretreating with liquor was most commonly used, and this scheme was colorfully drawn in Bu Yi Lei Gong Pao Zhi Bian Lan (Ming Dynasty, 1591 CE) ; moreover, decocting in advance or long-time simmering so as to prepare paste products were recommended in the Qing Dynasty. (6) Some different processing programs involving stir-baking with grit, air-tightly baking with ondol (Kangs), fumigating with sulfur, which appeared in modern times and brought attractive outward appearance of the drug, went against ancients original intentions of ensuring drug efficacy. PMID- 26666047 TI - [Spectroscopic characteristics of novel Psidium meroterpenoids isolated from guava leaves]. AB - Recently, novel Psidium meroterpenoids were reported in the guava leaves. According to careful analysis of the spectral data of literatures, the spectroscopic characteristics and biosynthetic pathway of Psidium meroterpenoids were summarized in this paper. The results showed that Psidium meroterpenoids had distinct spectroscopic features and reasonable biosynthetic routines, however the number order of carbon atoms was not consistent in the reported literatures. It was concluded that Psidium meroterpenoids were the characteristic chemical constituents of Psidium guajava Linn. PMID- 26666048 TI - Coping with the Holidays. PMID- 26666049 TI - The Resolution Revolution. PMID- 26666050 TI - Growing passion. PMID- 26666051 TI - For the Way You Live. PMID- 26666052 TI - Holiday Dinner. PMID- 26666053 TI - Cooking for Company. PMID- 26666054 TI - Open House. PMID- 26666055 TI - Visions of Sugarplums. PMID- 26666056 TI - The Type 1 Diagnosis. PMID- 26666057 TI - The symptomless condition. PMID- 26666058 TI - Charlie Kimball. PMID- 26666059 TI - The Storm Over Volkswagen. PMID- 26666060 TI - Essential Care for Essential Protection. PMID- 26666061 TI - New OSHA Rescue Requirements for Confined Space Retrieval: What You Should Know. PMID- 26666062 TI - Selecting the Right Ventilation Equipment When Working in Confined Spaces Under the New Construction Standard. PMID- 26666063 TI - Righting Respirator Wrongs: Correcting Misconceptions for Greater Respiratory Protection. PMID- 26666064 TI - Protect Your Hands and Your Livelihood. PMID- 26666065 TI - Perfect Foresight: Making Hazardous Chemical Safety Procedures a Priority. PMID- 26666066 TI - Four Tips for Keeping Your Hands Toasty While Working in the Cold. PMID- 26666067 TI - New Global Standards for Protective Gloves Are Coming. PMID- 26666068 TI - Training to Become a Fall 'Pro' Is a Never-Ending Journey. PMID- 26666069 TI - A Spill, a Slip, a Hospital Trip. PMID- 26666070 TI - Clearing the Air About Disposable Dust Masks. PMID- 26666071 TI - Five Reasons You Have Undesired Performance. PMID- 26666072 TI - Leadership: Going Through the Hoops. PMID- 26666073 TI - A Near Collision With Benefits for Many. PMID- 26666074 TI - Reflections on Modem Dental Ceramics. PMID- 26666075 TI - FOCUS ON: Prosthodontics. PMID- 26666076 TI - Vitamin B12 and Dentistry. PMID- 26666077 TI - Observations on Current Controversies in Dentistry. PMID- 26666078 TI - Reciprocation: A Safer and More Efficient Approach to Care. PMID- 26666079 TI - Bone Grafting for Dental Implant Placement. PMID- 26666080 TI - Surgical Techniques to Increase Bone Augmentation Success. AB - Oral implantology has grown into awidely acceptedand ever expanding discipline. Due to this phenomenon, more and more clinicians are offering dental implant surgery in their respective practices. As the discipline of implantology grows, the prevalence of bone grafting will become more significant. Restoring the lost hard-tissue volume to allow ideal implant placement. is crucial to decrease the Morbidity of implants and the restorations they support. Bone augmentation comprises a wide range of materials, donor sites, and surgical approaches, with new advances arriving at a staggering rate. With all of the materials and varying techniques available today, the practitioner must have a solid understanding of adjunct techniques to increase the success of bone grafting. PMID- 26666081 TI - Unique Solution for Porcelain Fracture: A Case Report. PMID- 26666082 TI - A Biomimetic Approach to Treating Aggressive Caries. PMID- 26666083 TI - Accelerated Treatment in a Multidisciplinary Case. PMID- 26666084 TI - Rehabilitation of Mandibular Atrophy: The Case of the Prolonged Partial. PMID- 26666085 TI - Evolution of Comprehensive Care, Part 5: Restoring Endodontically Treated Teeth and Advances in Fixed Restorations. PMID- 26666086 TI - Individual vs. Employer-Based Health Care: Changing Solutions for Discrete Populations. AB - The Affordable Care Act has served as a catalyst for the changes currently underway in the U.S. health care system and accelerated change underway over the past two decades. Employers are striving to make sense of an evolving health environment while meeting the needs of an increasingly diverse workforce. The health care landscape has shifted from the "Era of the Health Plan" to the "Era of the Person," where employers must pay heed to the distinct needs of each discrete population. To achieve optimal business performance, employers must adopt differentiated solutions that make health care local, personal and specific. PMID- 26666087 TI - Fine-Tuning the Impact of "Play or Pay" Strategies: Evaluating Compensation Adjustments. AB - One of the options available to employers under the Affordable Care Act is to drop health care coverage, pay a penalty and provide some form of additional compensation to employees. This article describes a process for evaluating this option, including considerations for establishing the amount of compensation to be provided, if any. It identifies a number of complexities and provides hypothetical examples of how employers might apply this option to employees with different salaries, ages and family statuses. PMID- 26666088 TI - Restructuring Employee Benefits to Meet Health Care Needs in Retirement. AB - Health care expenses in retirement are the proverbial elephant in the room. Most employees don't know how big the elephant is. As Medicare solvency and retiree health care issues receive increasing attention, it is time to rethink overall benefit approaches and assess what is appropriate and affordable for an organization to help achieve workforce renewal goals and solve delayed retirement challenges. Just as Medicare was never designed to cover all of the post-65 retiree health care costs, neither is a workplace retirement plan designed to cover 100% of preretiree income. Now employers can consider strategies that may better equip retirees to meet both income needs and health care expenses in the most tax-efficient way. By combining defined contribution retirement and health care plans, employers have the power to increase benefits for employees while maintaining total benefits cost. PMID- 26666089 TI - Health Care Consumerism: Lessons My 401(k) Plan Taught Me. AB - Changes to the U.S. health care system are here. As we think about how individuals will pay for health care--while actively employed and while retired- our experiences with 401(k) plans provide some valuable lessons. In order to support employees in this new health care world--a challenge arguably more daunting than the 401(k) challenge we faced 20 years ago--some very different types of support are needed. Employers should consider providing their employees with the resources to manage health care changes. PMID- 26666090 TI - Step Into Patients' Shoes: How to Understand and Apply a Patient-Centered Perspective. AB - Is your health plan truly encouraging employees to be health care consumers? Research in health literacy and patient health engagement may unlock new solutions. This article offers concrete ways employers can shift their frame when designing and communicating health plans, empowering employees to be better self advocates. PMID- 26666091 TI - Strategic Planning for Health Care Cost Controls in a Constantly Changing Environment. AB - Health care cost increases are showing a resurgence. Despite recent years' comparatively modest increases, the projections for 2015 cost increases range from 6.6% to 7%--three to four times larger than 2015's expected underlying inflation. This resurgence is just one of many rapidly changing external and internal challenges health plan sponsors must overcome (and this resurgence advances the date when the majority of employers will trigger the "Cadillac tax"). What's needed is a planning approach that is effective in overcoming all known and yet-to-be-discovered challenges, not just affordability. This article provides detailed guidance in adopting six proven strategic planning steps. Following these steps will proactively and effectively create a flexible strategic plan for the present and future of employers' health plans that will withstand all internal and external challenges. PMID- 26666092 TI - Catastrophic Medical Claimants After ACA's Removal of Annual and Lifetime Limits. AB - Among the many provisions of the Affordable Care Act, one that initially received lesser attention or concern was the removal of annual or lifetime dollar maximums on group and individual health insurance. It was a rare occurrence for claimants to even approach the formerly lofty limit of perhaps $1 million or $2 million lifetime. However, their removal has aligned with a significant uptick in severely catastrophic claimants--particularly those in excess of $1 million or more. The drivers are several, and alert plan sponsors need to take proper actions to protect the financial viability of their self-funded medical plans. PMID- 26666093 TI - GENDER-ASSOCIATED DIFFERENCES IN ACUTE HEART FAILURE PATIENTS PRESENTING TO EMERGENCY DEPARTMENT. AB - Little is known about gender-associated differences in characteristics and survival of acute heart failure patients. The increasing incidence calls for investigating the possibilities of improved management. The purpose of the study was to determine gender-associated differences among emergency department acute heart failure patients in order to improve treatment quality and survival. A prospective observational study on 22,713 patients was conducted at the University Hospital Center Emergency department during 2010 and included 726 consecutive acute heart failure patients. The most common cause of acute heart failure was worsening of chronic heart failure. Females suffered more frequently from hypertensive acute heart failure and males from acute heart failure associated with acute coronary syndrome. Females were older, with higher body mass index, atrial fibrillation, urinary tract infections, hypertension history, hypertension at admission, and SAPS II score at admission. Males had a higher frequency of ST-elevation myocardial infarction and dilated cardiomyopathy, confirmed by ultrasound as lower ejection fraction and left ventricle dilatation with reduced ejection fraction. Males were more frequently smokers with a history of chronic obstructive pulmonary disease. The importance of treating hypertension and atrial fibrillation in women and acute coronary syndrome and chronic obstructive pulmonary disease in men should be emphasized. Aggressive identification and management of all possible heart failure etiologies should be recommended in the emergency department. PMID- 26666094 TI - CO-OCCURRENCE OF CHRONIC HEAD, FACE AND NECK PAIN, AND DEPRESSION IN WAR VETERANS WITH POST-TRAUMATIC STRESS DISORDER. AB - This study investigated the relationship between chronic head, face and neck pain, and the level of depression in Croatian war veterans with post-traumatic stress disorder (PTSD). The presence of self-reported pain, pain on digital palpation, and pain severity in masticatory and neck muscles, temporomandibular joints and sinuses, as well as the level of depression were assessed in a group of war veterans with PTSD (n=52). Control groups consisted of war veterans without PTSD (n=50) and healthy men that were not engaged in war actions and were free from PTSD (n=50). The number of self-reported pain and number of painful sites were correlated with the level of depression. More self-reported pain and painful sites were recorded in the group of war veterans with PTSD as compared with either war veterans without PTSD or healthy men. Furthermore, PTSD patients mostly suffered from severe depression. There was a statistically significant positive correlation between all investigated pain parameters and level of depression. As the most important finding, the present study demonstrated chronic head, face and neck pain to be related to depression in PTSD patients. PMID- 26666095 TI - VALIDATION STUDY OF THE TORONTO ALEXITHYMIA SCALE (TAS-26) IN CROATIAN POPULATION. AB - The aim of this study was to validate the Croatian translation of the Toronto Alexithymia Scale (TAS-26). For this purpose, 194 volunteers from the general population, both genders, aged between 18 and 60, were tested on this scale after it had undergone a repeated back-translation procedure by an independent bilingual translator. The mean total score on TAS-26 (mean +/- SD) was 72.9+/ 8.4. Cronbach's alpha-coefficient for the entire scale was 0.71, indicating the scale to be sufficiently reliable. When analyzing the alpha-coefficient of reliability for the entire scale, it was found that upon removal of one of the factors, only 3 factors ('I have physical sensations that even doctors don't understand'; 'When I'm upset, I don't know if I'm sad, frightened, or angry'; and 'I have feelings that I can't quite identify') would determine the alpha coefficient of the entire scale amounting to less than 0.67, which would indicate insufficient reliability of the scale. The aforementioned factors belong to the group of F1 facet factors, the facet around which most items are grouped (n=12) and therefore the scale would be reliable enough even without the three factors. The results of factor analysis in our study confirmed the four-factor structure wherein most items are saturated by the first factor (n=12), and it denotes the alexithymia facet F1 (difficulty identifying feelings). Five items are saturated by the second factor and it denotes the alexithymia facet F2 (difficulty describing feelings), and the third factor which denotes facet F3 (reduced daydreaming) also saturated five items, whereas the fourth factor which denotes facet F4 (externally oriented thinking) saturated four items. The four listed facets explain 47.2% of variance wherein the highest percentage (20.1%) is attributed to facet F1, with facet F2 accounting for 12.1%, facet F3 for 7.5%, and facet F4 for 6.6% of variance. PMID- 26666096 TI - SIGNIFICANCE OF FIBROBLAST GROWTH FACTOR 23 IN ACUTE KIDNEY INJURY. AB - Acute kidney injury is a clinical syndrome associated with increased patient morbidity and mortality, as well as serious short-term and long-term consequences, especially in the perioperative period. Yet, patients having suffering from temporary acute kidney injury and achieving full recovery of kidney function usually complain of poor quality of life associated with loss of energy and limited physical activity. Therefore, there is a necessity for a novel biomarker of acute kidney injury with better features than currently used serum creatinine and urine output. So far, several investigations have demonstrated that the fibroblast growth factor 23 could be that desperately searched novel biomarker of acute kidney injury. It cannot only detect kidney dysfunction at the time but also before the injury process begins. Moreover, serum levels of the fibroblast growth factor 23 can predict adverse progression of the kidney injury. However, the role of the fibroblast growth factor 23 in the acute but also in chronic kidney dysfunction is still a riddle that requires additional research to clarify it. PMID- 26666097 TI - INTRAOPERATIVE ANEURYSMAL RUPTURE: CLINICAL OUTCOME FOLLOWING OPEN SURGERY OR ENDOVASCULAR TREATMENT. AB - The aim of this study was to evaluate and compare the outcomes of intraoperative aneurysmal rupture in patients with subarachnoid hemorrhage undergoing open surgical or endovascular treatment. This retrospective study included 742 patients with aneurysmal subarachnoid hemorrhage treated at the Clinical Department of Neurosurgery, Clinical Center of Serbia, during a three-year period. Among them, 167 (31.15%) were treated by clipping and 33 (16.01%) by coiling in the early phase (<=72 hours). The overall outcome and pretreatment variables were analyzed for each group, including between-group difference according to the occurrence of intraoperative aneurysmal rupture. Intraoperative aneurysmal rupture occurred in 14.7% of microsurgical and 2.4% of endovascular procedures. It was more frequent in early procedures as compared with delayed procedures (27.5% and 9.7% vs. 2.2% and 1.1%, respectively). On the contrary, mortality rates were lower in the surgical group (11.4%) than in the endovascular one (60.0%). On the basis of the results obtained, it is concluded that intraoperative aneurysmal rupture is more frequent after open than after endovascular treatment, but clinical outcome is more favorable in the former group. PMID- 26666098 TI - DEMOGRAPHIC AND CLINICOPATHOLOGIC FEATURES OF PATIENTS WITH PRIMARY BREAST CANCER TREATED BETWEEN 1997 AND 2010: A SINGLE INSTITUTION EXPERIENCE. AB - Breast cancer accounted for 28% of all new cancers and 18% of female cancer deaths in Europe in 2010. It is the most common type of cancer in women in Croatia, with an incidence rate of 56.9/100 000 in the year 2010, and the highest number of newly diagnosed women aged between 60 and 64. Multiple factors are associated with an increased risk of breast cancer: advancing age, family history, exposure to endogenous and exogenous reproductive hormones, dietary factors, benign breast disease, and environmental factors. To assess demographic and clinicopathologic features of primary breast cancer, we retrospectively analyzed 870 patients treated in our institution between 1997 and 2010. Data were obtained from medical documentation and a printed questionnaire regarding life habits. Most of our patients presented with a breast lump and were self-diagnosed by breast examination. This fact highlights the need of regular breast self examination, although it should also be taken into account that most of our patients did not attend regular mammography screening (only 31%). One of the most concerning facts is that the mean time from observing the first symptom to visiting a physician was 4 months. Previous studies have identified ignorance, fear and fatalistic attitudes, poor socioeconomic conditions, and illiteracy as important factors resulting in delay. Considering these facts, education and raising awareness about the disease in the general population is one of the key weapons for lowering breast cancer mortality. PMID- 26666099 TI - MAGNETIC RESONANCE IMAGING TO EVALUATE NEOADJUVANT THERAPY EFFECTS ON RECTAL CARCINOMA. AB - Although total mesorectal excision reduces the local recurrence rate in comparison to other surgical approaches, the occurrence of local relapse is still common, especially in cases when there is malignant infiltration of the circumferential resection margin. Mesorectal fascia is an important prognostic and diagnostic factor and it may be argued that mesorectal fascia represents the circumferential resection margin if total mesorectal excision is used as a surgical approach. Tumor infiltration of mesorectal fascia warrants preoperative neoadjuvant therapy in order to reduce the risk of tumor relapse. The aim of this study was to show the importance of high-resolution phased-array magnetic resonance imaging (MRI) as a modality of choice in preoperative evaluation of the effects of neoadjuvant therapy on locally advanced rectal carcinoma. This prospective comparative study included 51 patients with locally advanced rectal carcinoma that infiltrated mesorectal fascia. All study patients underwent MRI scanning twice, i.e. before and after neoadjuvant chemoradiotherapy. MRI results before and after neoadjuvant chemoradiotherapy were compared to evaluate regression of tumor length and regression of tumor infiltration of mesorectal fascia. Gender distribution of 51 patients with rectal carcinoma subjected to neoadjuvant therapy was equal, and their average age was 51 (32-81) years. MRI results showed tumor regression from mesorectal fascia following chemoradiotherapy in 36 (70.5%) cases, and Wilcoxon test showed significant differences between pretherapeutic and post-treatment MRI findings (Z=-3.162, p=0.002) in the sense of regression of tumor infiltration of mesorectal fascia. In 41 (80.3%) cases there was a reduction of tumor length, where Wilcoxon test showed differences between pretherapeutic and post-treatment MRI findings (Z= 2.754, p=0.006) in the sense of tumor length reduction. The mean pretherapeutic tumor length was 5.4 (2.3-15) cm. The mean reduction of tumor length following chemoradiotherapy was 3.56 (0.3-4.1) cm. In all 36 patients that had tumor-free mesorectal fascia following surgical treatment, the post-treatment MRI results were confirmed by histopathology. In conclusion, MRI is important for evaluation of tumor infiltration of mesorectal fascia, and is useful on patient selection for appropriate treatment for rectal carcinoma. MRI reliably evaluates the effects of neoadjuvant therapy, which contributes to better outcome of treatment for this disease. PMID- 26666100 TI - QUALITY OF LIFE AND PERCEPTION OF DISEASE IN PATIENTS WITH CHRONIC LEG ULCER. AB - Chronic wounds on lower extremities most commonly result from chronic venous insufficiency. Chronic leg ulcer impacts the quality of life in a number of ways such as reduced mobility, pain, unpleasant odor, sleep disturbances, social isolation, etc. This study included 100 patients with chronic wounds/lower leg ulcer (59% of women and 41% of men, aged 31 to 89) treated locally with special wound dressings for moist wound healing. Study results showed no age and sex correlation with the quality of life, and all participants evaluated their quality of life and health satisfaction as neither good nor bad, but it was found that the disease mostly affected social relationships and to a lesser extent patient satisfaction with their physical and mental health, and the environment. Results on the disease perception showed that the participants considered their disease to have a significant effect on their life and would last for a relatively long time, but they also believed they had good control of their disease. Also, they considered the disease to have many symptoms affecting them; they were worried about their disease which they understood relatively well; they were aware that treatment could be very helpful; and that the disease had moderate effect on their emotional health. According to sex, the disease was found to have greater effect on women (especially on their emotional condition) and women had more faith in successful treatment, while correlation with age was nonsignificant. This study confirmed the importance of the patient psychological condition and the need of due care of their psychological reactions to and facing with the disease. PMID- 26666101 TI - FINE-NEEDLE ASPIRATION CYTOLOGY OF HEAD AND NECK LYMPH NODES IN A TEN-YEAR PERIOD - SINGLE CENTER EXPERIENCE. AB - A wide spectrum of diseases including reactive processes, infections, lymphomas and metastatic tumors can cause enlargement of lymph nodes. The present study on 4062 patients with lymphadenopathy was conducted in the Department of Cytology, Sestre milosrdnice University Hospital Center, Zagreb, during a 10-year period. Of 4062 patients with lymphadenopathy, 1624 were males and 2438 were females, age range from several months to 85 years. Of 4062 fine needle aspiration procedures, 232/4062 (5.7%) samples were nondiagnostic. Lymph node aspirates were benign in 2640/3830 (69%) and malignant in 1190/3830 (31%) cases. Hematologic disease (Hodgkin lymphoma and non-Hodgkin lymphoma) was diagnosed in 482/1190 (40.5%) and metastases in 708/1190 (59.5%) cases. Of 482 patients with hematologic disease, 48/482 (10%) had Hodgkin lymphomas and 434/482 (90%) non-Hodgkin lymphomas. In the group of malignant lymphadenopathy, there were 212/708 (30%) metastatic squamous cell carcinomas, 177/708 (25%) metastatic adenocarcinomas, 149/708 (21%) metastases of other carcinomas, and 170/708 (24%) metastases of other malignant tumors. The present study confirmed the fine needle aspiration cytology of enlarged head and neck lymph nodes to be an excellent first-line method to investigate the nature of the lesions. PMID- 26666102 TI - TREATMENT OF MEDIAL MENISCUS INJURY WITH PARTIAL MENISCECTOMY. AB - Partial meniscectomy involves partial removal of the meniscus. This can vary from minor trimming of the damaged part of the meniscus to the removal of the rip from the meniscocapsular junction. Meniscus tears are the most common knee injury. They may occur in acute knee injuries in younger patients, or as part of a degenerative process in older individuals. The aim of the study was to demonstrate the method of choice for treatment of medial meniscus injuries that, in well selected cases, resulted in a small rate of complications and fast rehabilitation. The study analyzed the results of arthroscopic partial medial meniscectomy in 99 patients, in the period from 2005 to 2013, with follow up of 12-14 months. In our series of arthroscopically treated medial meniscus, tears were found in 29 patients with vertical complete bucket handle lesions, 14 with vertical incomplete lesions, 9 with longitudinal tears, 13 with oblique tears, 11 with complex, flap and degenerative lesions, 10 with radial lesions and 13 with horizontal lesions. The mean preoperative International Knee Documentation Committee score was 52.52%, then 81.81% at one month and 92.92% at six months of arthroscopic partial medial meniscectomy. Arthroscopic partial medial meniscectomy is a minimally invasive diagnostic and therapeutic procedure. This procedure is an acceptable and effective long-term treatment, particularly in patients without significant articular cartilage damage, and is associated with minimal morbidity. PMID- 26666103 TI - USEFUL TECHNIQUE FOR ALLOGRAFT BONE HARVEST. AB - Although regarded as a gold standard, harvesting of autologous bone graft is associated with donor site morbidity and a number of complications. An alternative is allograft with limited availability as the main shortcoming. Femoral heads as allografts are now routinely obtained during total hip arthroplasty. A small but valuable amount of pure cancellous bone graft of high quality can be obtained in addition. An additional harvest site is the proximal metaphyseal region of femur. We present a simple, useful and inexpensive technique for one harvest that can be performed utilizing ordinary instruments. PMID- 26666104 TI - EPIDURAL ANALGESIA IN LABOR - CONTROVERSIES. AB - Labor pain is one of the most severe pains. Labor is a complex and individual process with varying maternal requesting analgesia. Labor analgesia must be safe and accompanied by minimal amount of unwanted consequences for both the mother and the child, as well as for the delivery procedure. Epidural analgesia is the treatment that best meets these demands. According to the American Congress of Obstetrics and Gynecology and American Society of Anesthesiologists, mother's demand is a reason enough for the introduction of epidural analgesia in labor, providing that no contraindications exist. The application of analgesics should not cease at the end of the second stage of labor, but it is recommended that lower concentration analgesics be then applied. Based on the latest studies, it can be claimed that epidural analgesia can be applied during the major part of the first and second stage of labor. According to previous investigations, there is no definitive conclusion about the incidence of instrumental delivery, duration of second stage of labor, time of epidural analgesia initiation, and long term outcomes for the newborn. Cooperation of obstetric and anesthesiology personnel, as well as appropriate technical equipment significantly decrease the need of instrumental completion of a delivery, as well as other complications encountered in the application of epidural analgesia. Our hospital offers 24/7 epidural analgesia service. The majority of pregnant women in our hospital were aware of the advantages of epidural analgesia for labor, however, only a small proportion of them used it, mainly because of inadequate level of information. PMID- 26666105 TI - LOW RISK PROSTATE CANCER: ACTIVE TREATMENT OR ACTIVE SURVEILLANCE? AB - The widely used screening for prostate cancer with prostate specific antigen has resulted in identification of potentially lethal prostate cancers at a much more curable stage and has been associated with significant falls in prostate cancer mortality. In spite of the fact that prostate cancer is one of the deadliest malignancies in men, the advent of sensitive diagnostic testing has also resulted in detection of low risk cancers due to the high incidence of latent prostate cancer in aging men and prolonged natural history of the disease. This, in turn, has entailed the problem of cancer overdiagnosis and subsequent overtreatment. Approximately 6 times as many men will be diagnosed with the disease as will die from it. Active surveillance appeared as a response to the clearly documented risks of overdiagnosis and overtreatment of low risk prostate cancer for localized prostate cancer. It entails initial expectant management rather than immediate therapy, with 'curative-intent' treatment deferred until there is evidence that the patient is at an increased risk of disease progression. This approach attempts to balance the risks and side effects of overtreatment against the possibility of disease progression and lost opportunity for cure. A systematic literature review brings current knowledge on the subject. PMID- 26666106 TI - RESULTS OF CLAVICLE FRACTURE TREATMENT IN CHILDREN. AB - Treatment of clavicle fracture is principally outpatient. Operative treatment is accompanied by the need for more x-rays and possible complications. Fractures with absolute indications for operative treatment occur only sporadically and these indications are relatively clear, but children often undergo surgery because of relative indications (shortening, fragment displacement, multifragmentary fractures), which are open to debate. In a retrospective study on 256 children, of 44 (17%) patients that received operative treatment only one 17-year-old boy had an absolute indication for surgical intervention. Other indications were fragment distraction (22 mm on average), age, associated injuries, and multifragmentary fracture. The placement of K-wire of appropriate thickness is often difficult, since the wire tends to bend and break, and patients have to undergo two additional operations of plate and screw fixation and later removal. In this retrospective study, we considered the advantages of using titanium or an elastic steel pin. All patients had favorable outcome, although some experienced numbness around the operation scar (4.5%), skin infections around the wire (15%), and/or the implanted K-wire damage (7%). PMID- 26666107 TI - SEVEN-YEAR TRENDS IN THE CROATIAN PRIMARY PERCUTANEOUS CORONARY INTERVENTION NETWORK. AB - The authors investigated trends in the Croatian primary Percutaneous Coronary Intervention (pPCI) Network results among three consecutive time intervals (2005 2007, first phase; 2008-2009, second phase; and 2010-2011, third phase). Data on 5650 patients with acute myocardial infarction with ST-elevation (STEMI) transferred or directly admitted and treated with pPCI in 11 Croatian PCI centers during the study period were collected and analyzed. The number of patients with acute STEMI treated with pPCI per year rose continuously during the study period (581 vs. 1272 vs. 1949 patients/year). The patient risk profile worsened during the study period: age (60 vs. 61 vs. 63 years; p<0.01), anterior myocardial wall involvement (43% vs. 44% vs. 51%; p<0.01), shock rate (7% vs. 9% vs. 11%; p<0.05), and percentage of transferred patients (42% vs. 36% vs. 46%; p<0.01). While the door-to-balloon time shortened (108 vs. 98 vs. 75 min; p<0.01), the symptom onset-to-door time increased (130 vs. 175 vs. 195 min; p<0.01), but without statistically significant influence on the total ischemic time. Multivariate log-linear analysis eliminated influence of a higher risk profile on the results of treatment and yielded no statistically significant changes in final TIMI 3 flow (Thrombolysis In Myocardial Infarction 3), in-hospital mortality, and six-month mortality rate, but revealed a significant increase in the rate of angina pectoris (12 vs. 22 vs. 36%; p<0.01) and other major adverse cardiovascular events (MACE; 6 vs. 23 vs. 14%; p<0.01) during follow up. In conclusion, the Croatian pPCI Network continuously ensures very good results of STEMI treatment in this economically less developed European country despite worsening of the risk profile in treated patients and opening of new, less experienced PCI centers. The higher percentage of MACE over time could be explained by changes in the pPCI strategy introduced over time (the culprit lesion only) and higher availability of PCI centers for additional PCI after acute STEMI. However, there is room for improvement, especially in reducing prehospital delay. PMID- 26666108 TI - A CASE OF PROBABLE NEUROSARCOIDOSIS PRESENTING AS UNILATERAL OPHTHALMOPLEGIA. AB - Sarcoidosis is a multisystem disease of unknown etiology, characterized by the presence of noncaseating epithelioid granulomas and accumulation of T lymphocytes and mononuclear phagocytes, which damages the normal structure of tissues. Isolated form of neurosarcoidosis is very rare and difficult to diagnose and requires histologic confirmation of noncaseating granulomas in the nervous tissue. We report a case of a 55-year-old female who had probable isolated neurosarcoidosis based on magnetic resonance imaging findings of relapsing pachymeningitis with an inflammatory process in the apex of the right orbit and pseudotumor inflammation of the superior and lateral recti of the right eye. Diagnosis was further verified by positive response to dual corticosteroid and immunosuppressive therapy. Our case demonstrates the importance of considering isolated neurosarcoidosis as a potential underlying etiology of painful ophthalmoplegia, even without systemic manifestation of the disease. PMID- 26666109 TI - A RARE CASE OF SQUAMOUS CELL CARCINOMA IN URINARY BLADDER DIVERTICULUM SUCCESSFULLY TREATED BY BLADDER-SPARING SURGERY. AB - The aim is to report a rare case of squamous cell carcinoma arising in a urinary bladder diverticulum and present recent literature overview of treatment options. A 56-year-old man presented with intermittent hematuria. Ultrasound examination indicated primary carcinoma in the urinary bladder diverticulum. Diagnosis was confirmed with cystoscopy and computed tomography. Transvesical diverticulectomy with regional lymphadenectomy was undertaken. Two years after initial treatment, the patient was well without evidence of tumor relapse. This report implicates that although aggressive surgical approach is recommended in the majority of bladder diverticulum tumors, simple diverticulectomy may be indicated in selected, confined cases. PMID- 26666110 TI - SPONTANEOUS HETEROTOPIC, ECTOPIC CERVICAL AND ECTOPIC TUBAL PREGNANCY - EVER PRESENT DIAGNOSTIC DIFFICULTY: THREE CASE REPORTS. AB - The incidence of heterotopic/ectopic pregnancy in recent times has increased partly due to the increase in assisted reproductive technologies, whereas such medical cases and cervical pregnancy in particular are extremely rare with spontaneous conception. We report on three patients referred to our department in one week: one patient each with spontaneous heterotopic pregnancy, cervical pregnancy and tubal pregnancy. All of them had conceived spontaneously and were properly diagnosed and treated, however, additional care is needed in diagnosing and managing the potentially fatal consequences of ectopic pregnancy if not recognized early and managed properly, despite its low incidence. PMID- 26666111 TI - UNUSUAL CLINICAL CASES THAT MIMIC ACUTE DISSEMINATED ENCEPHALOMYELITIS. AB - Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically. PMID- 26666112 TI - OROFACIAL GRANULOMATOSIS: CASE REPORT. AB - An 18-year-old girl was referred to the Department of Oral Medicine with upper lip swelling. She was in good general health and laboratory tests were within the normal range. Histopathologic diagnosis did not reveal the presence of granulomas. This is consistent with the finding that 30% of patients with orofacial granulomatosis do not have granulomas on their biopsies. The patient was treated with intralesional steroids once a week for three weeks. The lesion subsided, but not completely, and recurred partially after ketchup intake. This case report highlights the fact that in every patient with non-odontogenic facial or oral swelling, systemic diseases such as sarcoidosis, Crohn's disease, tuberculosis, etc. must be excluded. Furthermore, it is not unusual that in patients with orofacial granulomatosis, noncaseating granulomas are absent in the histopathologic finding. PMID- 26666113 TI - USE OF RECOMBINANT ACTIVATED FACTOR VIIa IN A-SIX-MONTH-OLD CHILD DUE TO MASSIVE HEMORRHAGE DURING ELECTIVE SURGERY FOR CHOROID PLEXUS CARCINOMA: CASE REPORT. AB - We present the use of recombinant activated factor VIIa (rFVIIa) in a 6-month-old infant that suffered massive bleeding and subsequent coagulation disturbances during elective surgery for choroid plexus carcinoma in the lateral ventricle. The administration of rFVIIa resulted in good hemostasis. No intra- or postoperative thromboembolic complications were observed. PMID- 26666114 TI - Sixty-Seventh Anniversary of the Clinical Department of Traumatology, Sestre milosrdnice University Hospital Center, Zagreb, Croatia. PMID- 26666115 TI - [Do biological assemblages and ensembles really exist?]. AB - In recent years the terms assemblage and ensemble have become more frequent in the ecological literature. After analyzing the definitions of the words in the French original, as well as their use in English and Spanish and opinions on how they can be defined, I conclude that the words assemblage and ensemble rarely improve scientific communication and can be eliminated from most ecological articles. The few justified exceptions are articles in which the emphasis is on how taxonomically close species interact trophically. PMID- 26666116 TI - Is forest cover conserved and restored by protected areas?: The case of two wild protected areas inthe Central Pacific of Costa Rica. AB - Changes in land use are mainly a consequence of anthropogenic actions. The current agricultural and urban transformations in Costa Rica have raised questions about the effectiveness of conservation and restoration within protected areas. Herein we analyzed the patterns of land use change between three periods: 1997, 2005 and 2010 in terms of magnitude, direction, and pace through categorical maps generated by the photointerpretation for La Cangreja National Park (LCNP), Rancho Mastatal Wildlife Refuge (RMWR), and their surrounding areas (SA), this last compound of one kilometer radius outside the protected areas' boundaries. The matrix which describes the landscape within the protected areas is natural coverage, composed mainly by forest cover and thickets. We found that the most abundant natural cover for both protected areas was forest cover for all years tested. The stability and large areas of forest cover in LCNP and RMWR for 2005 and 2010, reflected that policies, management actions and vigilance, have a positive impact on the conservation and restoration of natural habitats in these Costa Rican Central Pacific areas. However, the high landscape complexity of the SA in 1997, 2005 and 2010 was an evidence of the anthropogenic pressure on these protected areas, and suggested the ineffectiveness of local governments to monitor and abate land use changes, that could hinder the management, conservation and restoration of species in the protected areas. PMID- 26666117 TI - [Sedimentological Implications of the change in the coverage of mangrove forest in Boca Zacate, Terraba-Sierpa National Wetlands, Costa Rica]. AB - In the last sixty years many geomorphological changes have occurred in Costa Rica's Terraba-Sierpe National Wetlands. Changes in coastal geomorphology are generally associated with erosion or accretion of sediment, which has led to the removal of sections of mangrove forests or sediment banks colonized by mangroves. The aim of this study was to analyze sedimentation as a leading process in the dynamics of coastal morphology and its implications for mangrove forest cover in the Boca Zacate area of Terraba-Sierpe wetlands. The study was conducted in the sectors of Bocon, Brujo and Coco Island in Boca Zacate, from 2008 to 2013. The research was based on a multi-temporal analysis of coastal morphology using aerial photographs from the years 1948, 1960, 1974, 1978, 1984, 1992 and 2011. The following measurements were also performed: monthly sedimentation rate (g/cm2/day), and granulometric composition and content of chemical elements in the sediments of the study area. These last two measurements were performed once each in the dry and rainy seasons during the years of study. The results indicated that over the past 60 years, Boca Zacate has witnessed a process of sustained erosion; from 1948 through 2001, losing 10.6 % of its land and approximately 8.9 % of its forest cover. It has also experienced accretion in the area of Coco Island. The Brujo sector showed the highest sedimentation rate and the Camibar estuary, the lowest. The dominant type of sediment in all study sites was sand, followed by clay and silt. The most widespread chemical elements (mg/L) included magnesium, calcium and potassium; others, such as manganese, iron, aluminum, phosphorus, zinc and copper, were measured in smaller amounts. Transport, composition and quantity of sediment in Boca Zacate are crucial to the changes that have occurred on the coastal area of La Boca, where the presence of dead trees was evident. This geomorphological analysis holds great importance for future guidelines and actions for the conservation and integrated management of the mangrove in Terraba-Sierpe National Wetlands. PMID- 26666118 TI - [Diversity, structure and regeneration of the seasonally dry tropical forest of Yucatan Peninsula, Mexico]. AB - Seasonally dry tropical forests are considered as the most endangered ecosystem in lowland tropics. The aim of this study was to characterize the floristic composition, richness, diversity, structure and regeneration of a seasonally dry tropical forest landscape constituted by mature forest, secondary forest and seasonally inundated forest located in the Northeastern part of the Yucatan Peninsula, Mexico. We used the Gentry's standard inventory plot methodology (0.1 ha per forest type in 2007) for facilitating comparison with other Mesoamerican seasonally dry tropical forests. A total of 77 species belonging to 32 families were observed in the study area. Fabaceae and Euphorbiaceae were the families with the largest taxonomic richness in the three forest types. Low levels of beta diversity were observed among forest types (0.19-0.40), suggesting a high turnover of species at landscape level. The non-regenerative species were dominant (50-51 %), followed by regenerative species (30- 28 %), and colonizer species (14-21 %) in the three forest types. Zoochory was the most common dispersal type in the study area. The 88 % of the observed species in the study area were distributed in Central America. Some floristic attributes of the seasonally dry tropical forest of the Yucatan Peninsula, fall into the values reported for Mesoamerican seasonally dry tropical forests. Natural disturbances contributed to explain the high number of individuals, the low number of liana species, as well as the low values of basal area observed in this study. Our results suggested that the seasonally dry tropical forest of Yucatan Peninsula seems to be resilient to natural disturbances (hurricane) in terms of the observed number of species and families, when compared with the reported values in Mesoamerican seasonally dry tropical forests. Nonetheless, the recovery and regeneration of vegetation in long-term depends on animal-dispersed species. This study highlights the importance of establishing multiple protected areas throughout the Mesoamerican seasonally dry tropical forest in order to conserve both alpha- and beta- diversity. PMID- 26666119 TI - Inter-cohort growth for three tropical resources: tilapia, octopus and lobster. AB - Growth parameters are an important component for the stock assessment of exploited aquatic species. However, it is often difficult to apply direct methods to estimate growth and to analyse the differences between males and females, particularly in tropical areas. The objective of this study was to analyse the inter-cohort growth of three tropical resources and discuss the possible fisheries management implications. A simple method was used to compare individual growth curves obtained from length frequency distribution analysis, illustrated by case studies of three tropical species from different aquatic environments: tilapia (Oreochromis aureus), red octopus (Octopus maya) and the Caribbean spiny lobster (Panulirus argus). The analysis undertaken compared the size distribution of males and females of a given cohort through modal progression analysis. The technique used proved to be useful for highlighting the differences in growth between females and males of a specific cohort. The potential effect of extrinsic and intrinsic factors on the organism's development as reflected in the size distribution of the cohorts is discussed. PMID- 26666120 TI - Abundance, diversity and community characterization of aquatic Coleoptera in a rice field of Northeastern Argentina. AB - Rice fields occupy large areas in Northeastern Argentina, and in Corrientes this widespead activity has become a feature in the landscape, as it is one of the main producing provinces. The aquatic Coleoptera is part of the fauna inhabiting these artificial environments but little is known about this group in irrigated rice fields. The aims of this study were to determine the diversity and species richness of coleopterans in a typical rice field, and to characterize the community of water beetles through different abundance models. For this, samples were collected from an active rice field located in "El Sombrero" town, in Corrientes Province, between November 2011 and April 2012. An entomological net of 30 cm diameter was used, and species richness, diversity and equitability were calculated monthly; besides, the community composition was characterized by means of rank-abundance models. A total of 74 species of aquatic coleopterans were identified. January and February resulted the months with the highest diversity. The aquatic Coleoptera species found in most of the sampled months were adjusted to the logarithmic rank-abundance model. The data suggests that, if it is properly managed, rice cropping in Northeastern Argentina can support a diverse aquatic coleopteran fauna. PMID- 26666121 TI - Growth and production of Donax striatus (Bivalvia: Donacidae) from Las Balsas beach, Gibara, Cuba. AB - Clams of the genus Donax are worldwide the dominating group of the invertebrate community on sandy beaches. They are primary consumers that provide a significant abundance and biomass to the ecosystem. In the Caribbean, Donax striatus has an important role for nature and human, nonetheless studies on the population dynamics of this beach clam are scarce and no information exists on secondary production of this species. Growth parameters and secondary production of D. striatus were estimated from February 2008 to November 2009 at Las Balsas beach, Northeastern Cuba, in order to provide basic information for management purposes. In each month 45 samples were taken by means of a PVC corer of 0.025 m2 area and sieved with a 1 mm mesh. Animals were measured and weighted with and without shell. A total of 5 471 specimens were collected during the sampling period. Shell length ranged from 2.7-33.3 mm. Growth parameters estimated from length frequency data were Linfinity = 36.1 mm, K= 0.8/yr and t0= 0.2/yr. The growth performance resulted in values of Phi'= 3.02. Life span was 2.4 yrs and mortality rate was 3.07 /yr. In 2008, mean abundance of D. striatus ranged between 17.1 - 770.7 ind./m2. In 2009 the lowest mean abundance was 34.4 and the highest was 892.5 ind./m2. During 2009 biomass and production was more than twice higher in comparison with 2008. Individual production showed highest values in the 24 mm shell size (3.74 g/m2.yr) and 25 mm (0.71 g/m2.yr), considering mass with shell and without shell, respectively. During 2009 abundance of individuals with 15 mm shell length or more increased resulting in higher biomass and production, compared to 2008. Using the conversion factor of wet mass to ash free dry mass (AFDM), annual production ranged between 2.87-6.11 g AFDM/m2.yr, resulting in a turnover rate (P/B) between 5.11 and 3.47 in 2008 and 2009, respectively. The rapid growth and high turnover rate of D. striatus suggest a rapid recovery of the population. These results support the idea that this beach clam is an important resource at Las Balsas beach. Thus its exploitation must continue with caution, and only at the level of a recreational fishery. PMID- 26666122 TI - Interaction networks and the use of floral resources by male orchid bees (Hymenoptera: Apidae: Euglossini) in a primary rain forests of the Choco Region (Colombia). AB - Orchid bees are important keystone pollinators from the Neotropics. With the aim to study the relationships between orchid bees and their nectar and aromatic host species, we made systematic samplings of males across two conservation areas in the biogeographic Choc6 Region of Colombia. We used chemical baits to collect 352 male bees during five months. The pollen attached to their bodies was extracted for palynological identification and to estimate interaction networks. The euglossine community consisted of at least 22 species including Eg. maculilabris, Eg. orellana, Eg. championi and Eg. ignita. The male bees were associated with 84 plants but depended on a small group of them (Peperomia spp. and Anthurium spp, as well as species of Solanaceae, Ericaceae and Malpighiaceae) which were widely distributed across the altitudinal gradient, and were available through the year. The resulting interaction networks revealed a typical nested pattern usually found in plant-pollinator interactions, with several rare bee and plant species interaction with a small group of generalist bees and plant species. Albeit, we found variation within networks related to species composition. Such variation may be a consequence of specific differences in plant flowering phenology. PMID- 26666123 TI - [Mites associated with two species of the genus Odontotaenius (Coleoptera: Passalidae) in Mexico]. AB - Mites can establish association with different arthropods as coleopterans tamites scaraoaeicae ana Passalidae. Passalids are distributed in tropical and templates zones, and until now, more than 200 species of mites have been associated to them. One of the relationships between passalids and mites is the phoresy where one small animal (the phoretic) seeks out and attaches to another animal (the host) for transportation. Herein, we studied the mites associated to O. zodiacus and O. striatopunctatus; for this, 80 Odontotaenius with mites were reviewed; passalids were collected in and under decaying logs from six states of Mexico, and were individually kept in vials with 80% ethanol. The specimens were carried to the laboratory and mites removed with fine-pointed forceps under stereo microscope. The mites were stored with 80 % alcohol until some were cleared with lacto-phenol and mounted in Hoyer's solution. We found 1,945 mites belonging to 13 families (Acaridae, Ascidae, Diarthrophallidae, Digamasellidae, Diplogyniidae, Euzerconidae, Heterocheylidae, Histiostomatidae, Klinckowstroemiidae, Laelapidae, Megisthanidae, Trematuridae, and Uropodidae) and 42 species, being the most abundant species Anoelus sp. For O. striatopunctatus (16 specimens) we found 562 mites (95 female female, 34 male male, 197 hypopus, 234 deutonymph, 2 tritonymph) of 11 families and 22 species; the most abundant were Uropodidae (42 %) and Histiostomatidae (26 %). While for 0. zodiacus (64 specimens) were found 1,383 mites (300 female female, 204 male male, 608 hypopus, 139 deutonymphs, 133 tritonymphs) of 10 families and 30 species; the most abundant were: Diartrophallidae, Acaridae, and Histiostomatidae (23 % for the two first and 21 % for third). The high abundance and richness was in O. zodiacus, likewise Margalef (S') and Shanon-Winner (H') indexes were higher in this species (O. zodiacus S' = 4.05, H' = 2.2; O. striatopunctatus S' = 3.34, H' = 1.94), while Equity (EH) was similar to both hosts (0. zodiacus EH = 0.64; O. siriatopunctalus EH = 0.63). The mites were found principally in the protected zone of the passalid's body, as under elytron, membranous wings, and in the clefts of the ventral region of the passalid, and, in minor proportion, on the head and coxal regions. From our findings, 12 species were new records for the Mexican passalids: Abrotarsala cuneiformis, A. obesa, A. pyriformis, Brachytremella sp., Diarthrophallus cartwrighti, D. crinatus, Lombardiniella sp., Trichodiplogynium carlosi, T sahlbergi, T hirsutum and Trichodiplogynium sp., and additional studies may help describe and understand these mites-passalids associations. PMID- 26666124 TI - Fluctuating asymmetry in Apis mellifera (Hymenoptera: Apidae) as bioindicator of anthropogenic environments. AB - The successful distribution of A. mellifera is due to their ability to adjust to seasonal variations, considerable control over their internal physical environment and exploration of different resources. However, their populations have experienced different forms and levels of environmental pressure. This research aimed to verify the phenotypic plasticity in both size and shape of wings in A. mellifera using fluctuating asymmetry, based on geometric morphometrics from apiaries located in sites with high and low levels of anthropization. We sampled 16 locations throughout all five geographic regions of Brazil. At each site, samples were collected from 20 beehives installed in apiaries: 10 installed near high anthropogenic environments (Cassilandia - MS, Fortaleza - CE, Maringa - PR, Aquidauana - MS, Rolim de Moura - RO, Riachuelo - SE, Ubirata - PR and Piracicaba - SP), and 10 in sites with low levels of human disturbance (Cassilandia - MS, Itapiuna CE, Uniao da Vitoria - PR, Aquidauana - MS, Rolim de Moura - RO, Pacatuba - SE, Erval Seco - RS, Rio Claro - SP). A sample of 10 individuals was taken in each hive, totaling 200 per location, for a total of 1,600 individuals. We used fluctuating asymmetry (FA) in size and shape of the forewing through geometric morphometrics. The FA analysis was conducted in order to check bilateral differences. The indexes of size and shape were submitted to analysis of variance (ANOVA), where the characters evaluated were used as factors to verify the size and shape differences. The results indicated an asymmetry on the shape of the wing (P < 0.001) but no asymmetry was observed on wing size. Considering FA as an environmental response and high and low impacted areas as a fixed factor, we observed significant differences (P < 0.05). The results for the wing shape in A. mellifera demonstrated that this feature undergoes more variation during ontogeny compared to the variation in size. We concluded that bee samples collected from colonies with higher levels of human disturbance had higher wing-shape asymmetry; the variation of fluctuating asymmetry in the wing shape of honeybees can be used as an indicator of the degree of environmental anthropization. PMID- 26666125 TI - Water pollution and distribution of the black fly (Diptera: Simuliidae) in the Atlantic Forest, Brazil. AB - Black flies have medical importance because some species are vectors of the unenocerciasis and Mansonelosis, nevertheless, their ecology and potential use as bioindicators is still poorly studied in the Neotropical Region. In Brazil, bioindicators use is strongly focused in a multimetrical ecological index approach; this way, we investigated the black fly spatial distribution, in relation to abiotic factors correlated to water quality, to provide baseline information for their utilization as standalone indicators of lotic systems integrity. We have tested the hypothesis that environmental changes related to urbanization, lead to decreased abundance and loss in the number of species of the black fly fauna. The sampling was conducted in 10 urban and 10 preserved streams during the dry season (August-September) of 2012, in the mountainous region of Teres6polis, State of Rio de Janeiro, Brazil. The streams were characterized for their environmental integrity conditions and physico-chemical properties of water. In each stream, five different rapid points were sampled in a section of 50 meters, 10 meters apart from each other. The black flies were sampled with a kick-net sampler on rocky substrates. The material was separated and the larvae were sorted in morphotypes, and later, the final instar specimens were dissected and identified with the help of taxonomical literature at species level. A total abundance of 488 larvae from nine species were collected, 5 (1.02 %) in extremely impacted streams, 470 (96.31 %) in intermediate streams and 13 (2.66 %) in preserved streams. The visual evaluation (HII) differed in relation to the water physico-chemical evaluation, in which more variation in the characterization of the sampling sites was observed. In Canonical Correspondence Analysis Simulium subpallidum, S. inscrustatum and S. pertinax were significantly associated with intermediate values of most of the variables, and then to intermediate impacted sites. On the other hand, Lutzsimulium hirticosta, S. subnigrzm and Simulium sp. A were associated to low values of chemical variables, and then to more preserved sites. Most studies on the bioindicator potential of Simuliidae have suggested an approach to agricultural impacts, while our results, on the other hand, showed that Simuliidae species were present in streams with intermediate urban pollution impacts, but absent in heavily impacted sites. Thus, our data suggested that some species are associated to more pristine breeding sites, such as L. hirticosta and Simulium sp. A, while others may be good bioindicators of moderately impacted streams, such as S. nertinax. S. subnigrum and S. subpallidum. PMID- 26666126 TI - Larval structure of Passalus gravelyi and sexual dimorphism in Passalid larvae. AB - The adults and larvae of Passalidae are subsocial insects commonly found in tropical forests, living in decaying wood gallery systems constructed by adults. Currently, few repots on the larvae of Neotropical Passalidae have been published and information is scarce. In this study, the Passalus (Pertinax) gravelyi Moreira, 1922 larvae is described for the first time, based on ten larval specimens 1 (1 degrees instar), 4 (2 degrees instar), and 5 (3 degrees instar) associated with three adults collected from a single colony at the Parque Nacional do Itatiaia (Itatiaia, Rio de Janeiro, Brazil). The description was carried out based on electronic and digital photographs of diagnostic structures, with some details on the systematic of the species. The larvae of Passalus gravelyi has the general setal 'Pertinax' pattern and differed from others by 16 to 18 setae on the anal ring, the other larvae data from Brazilian species show the anal ring with 10 to 12 setae. A discussion on the presence of sexual dimorphism in 62 species of two and three instars of Passalidae larvae is provided for the first time. Besides, a description of the terminal ampulla present as a cuticular structure found in the medial-ventral area of the 9th abdominal sternite in males is also given. The terminal ampulla was only observed in the Passalidae male larvae and was not visible in female larvae. The terminal ampulla are acknowledged now in males of 64 passalid species, that are taxonomically distributed in world tropical forests, at the Oriental and Australian subfamily Aulacocyclinae (Aulacocyclini & Ceracupini) and the cosmotropical subfamily Passalinae (Solenocyclini, Macrolinini, Passalini, & Proculini). PMID- 26666127 TI - Assessment of the dolphinfish Coryphaena hippurus (Perciformes: Coryphaenidae) fishery in Pacific Panama. AB - The dolphinfish (Coryphaena hippunis) is a highly migratory pelagic species commercially exploited by industrial, artisanal and recreational fisheries in tropical and subtropical areas of the world's oceans. Herein, we evaluated the dolphinfish industrial fishery in Pacific Panama for the first time generating a growth model and examining fluctuations in annual total catch and in catch per unit effort (CPUE) over a four-year period (2006-2009). Annual and monthly catch values and biological parameters of 14913 individuals were obtained onboard industrial vessels, landing sites and records from processing plants. Size frequency for industrial vessels showed a normal distribution between 353 and 1,715 mm (average, 1010.85 mm; n = 10,459). Fish weight averaged 4.94 kg (SD). Sex ratio was slightly biased toward females. More than 90% of the analyzed fish were sexually mature. The length-weight relationship was positive and significant, reflecting allometric growth. Growth parameters using the von Bertalanffy equation revealed a growth efficiency of theta = 4.61, which is within the reported range for Coryphaena hippurus (3.95-4.70). The largest fish were between age classes 2 and 3 (700 - 1400 mm). Total catch per year and catch per unit effort (CPUE) per year fluctuated, with the highest values recorded between 2008 and 2009. Catch values reported herein are preliminary and appear to be below those recorded elsewhere in the region and cautiously may represent an indicator of sustainable use of this marine resource even considering the absence of management actions in Panama. PMID- 26666128 TI - [Variations of the infracommuity during the ontogeny of Chromis cyanea (Perciformes: Pomcentride) in the North coast of Havana, Cuba]. AB - The infracommunty or parasites or unromis cyanea (Pisces: Pomacentridae) was studied along the ontogenetic development in the North coast of Havana, Cuba. The objectives were: a- to prove that the core species appears before the strange and stochastic species and they are responsible for the structure in the infracommunity, b- to determine if there is a relationship among the ecological describers of the parasitic infracommunity with the total length. A total of 278 specimens of C. cyanea were captured during the dry season (April) of 2010. The body size range was from 1.5 to 11.5 cm including juvenile and adults. We collected 2 861 parasite specimens belonging to 20 taxa: Crustacea (5), Nematoda (5), Trematoda (4), Cestoda (2), Monogenea (2), Turbellaria (1) and Ciliophora (1). The taxa Tetraphyllidea and Anilocra chromis constituted the core of the parasitic infracommunity. The sequence of appearance and persistence of these taxa during the ontogenetic development, supported the hypothesis of the core species. The changes in the infracommunity, from 6 cm body size, could be the result of an accumulative effect combined with changes of the diet that caused the ingestion of new parasite infective stages. We concluded that the ontogenetic development of C. cyanea constitutes an important variable in the formation of the parasitic infracommunity. PMID- 26666129 TI - Population structure and reproductive period of two introduced fish species in a Brazilian semiarid region reservoir. AB - The Amazonian fish species Plagioscion squamosissimus (Sciaenidae) and Cichla monoculus Cichlidae), have been widely introduced into different reservoirs in Brazil, and have caused many negative mpacts on local fish fauna. The aim of this study was to evaluate the population structure (abundance, length structure, length-weight relationship, sex ratio, and length at first maturity) and the reprodutive period of these wo species in the Santa Cruz Reservoir (built in 2002), located in the Brazilian semiarid region, for their adequate management and local species conservation policies. Specimens were collected quarterly in eight sites from February 2010 to November 2013 using gillnets (12 to 70 mm mesh between adjacent knots). The specimens captured were counted and the following biometric and biological data were analysed: standard length, total weight, and reproductive data, such as, sex, weight and gonadal maturity stage. The species abundances were estimated by CPUE and expressed as the number of individuals per gill net area x gill net exposition time (m2 x h); length frequency histograms were built with intervals of 5 cm. The length-weight parameters were estimated with a linear regression after a logarithmic transformation of the data. With the reproductive data we estimated sex ratio, reproduction period and length at first maturity (L50). We captured a total of 1,071 specimens of P. squamosissimus and 156 specimens of C. monoculus. Both species showed higher abundances in 2010, 0.004306 m2 x h and 0.00022 m2 x h, respectively, but this parameter decreased from 2010 to 2013. Standard length ranged between 6.4 and 46.2 cm for P. squamosissimus (20.025.0 cm was the most frequent class), and 7.0 and 38.7 cm for C. monocidus (10.0-15.0 cm was the most frequent class). The length-weight relationships were described by the following equations: log10Wt = 1.8349+3.0899log10Lp and R2= 0.9795 for P. squamosissimus, and log10 Wt = 1.7944+3.0885log10Lp and Wt = 0.0160 and R2 = 0.9929 for C. monoculus; both species exhibited positive allometric growth. The sex ratio for both species differed from 1:1, with a predominance of females for P. squamosissimus and males for C. monoculus. The Lp50 was estimated to be 15.90 cm for P. squamosissimus and 15.65 cm for C. monoculus, and the reproductive data indicated that both species reproduced throughout the year. We concluded that although the population of both species reduced their abundance over the study period, P. squamosissimus and C. monoculus are established and structured populations in the Santa Cruz Reservoir with individuals growing satisfactorily and reproducing in all seasons, without a well-defined reproductive peak. We suggest that the managers may allow the artisanal and/or sport fisheries of these species. PMID- 26666130 TI - [Determination of stress in fish community obtained from shrimp trawl fishing in Northern Gulf of California]. AB - Bottom trawling has been considered a fishing activity that affects and modifies habitats, because of its impacts in species composition and abundance, and the alteration in the structure and function of the eco-system, that generates biodiversity loss. The Northern part of the Gulf of California has been considered a mega diverse zone with high endemism, and it is of growing interest by the international scientific community. In order to assess its potential changes in the fish community components of shrimp by-catch (FAC) in this area, a total of 119 trawls from 13 fishing boats were analyzed in Puerto Penasco, based on 14 commercial fishing trips made within 9-90 m depth from 2010-2011. A random sample of 20 kg was obtained from each trawl, and was analyzed in the laboratory for species composition. In addition to the Index of Biological Value (IVB), Shannon diversity (H'), and Pielou evenness (J'), comparative abundance-biomass curves (ABC) were also estimated. Eucinostomus dowii showed the highest IVB = 480.25; Porichthys analis showed greater relative abundance; and Pomadasys panamensis showed greater frequency of occurrence. The mean monthly values in diversity H' = 3.05 (2.72 > H' < 3.25) and J' = 0.71 (0.66 < J' >0.81) showed a tendency to decrease as the fishing season progressed. The comparative abundance biomass curves (ABC), and the value of statistical W showed moderate stress levels in March (W= -0.022) and September (W= -0.02) 2010, and January 2011 (W= 0.042). In conclusion, the Northern Gulf of California showed a well-structured community with a degree of moderate fishing stress. PMID- 26666131 TI - Stock assessment of fishery target species in Lake Koka, Ethiopia. AB - Effective management is essential for small-scale fisheries to continue providing food and livelihoods for households, particularly in developing countries where other options are often limited. Studies on the population dynamics and stock assessment on fishery target species are thus imperative to sustain their fisheries and the benefits for the society. In Lake Koka (Ethiopia), very little is known about the vital population parameters and exploitation status of the fishery target species: tilapia Oreochromis niloticus, common carp Cyprinus carpio and catfish Clarias gariepinus. Our study, therefore, aimed at determining the vital population parameters and assessing the status of these target species in Lake Koka using length frequency data collected quarterly from commercial catches from 2007-2012. A total of 20,097 fish specimens (distributed as 7,933 tilapia, 6,025 catfish and 6,139 common carp) were measured for the analysis. Von Bertalarffy growth parameters and their confidence intervals were determined from modal progression analysis using ELEFAN I and applying the jackknife technique. Mortality parameters were determined from length-converted catch curves and empirical models. The exploitation status of these target species were then assessed by computing exploitation rates (E) from mortality parameters as well as from size indicators i.e., assessing the size distribution of fish catches relative to the size at maturity (Lm), the size that provides maximum cohort biomass (Lopt) and the abundance of mega-spawners. The mean value of growth parameters Linfinity, K and the growth performance index o' were 44.5 cm, 0.41/year and 2.90 for O. niloticus, 74.1 cm, 0.28/year and 3.19 for C. carpio and 121.9 cm, 0.16/year and 3.36 for C. gariepinus, respectively. The 95 % confidence intervals of the estimates were also computed. Total mortality (Z) estimates were 1.47, 0.83 and 0.72/year for O. niloticus, C. carpio and C. gariepinus, respectively. Our study suggest that O. niloticus is in a healthy state, while C. gariepinus show signs of growth overfishing (when both exploitation rate (E) and size indicators were considered). In case of C. carpio, the low exploitation rate encountered would point to underfishing, while the size indicators of the catches would suggest that too small fish are harvested leading to growth overfishing. We concluded that fisheries production in Lake Koka could be enhanced by increasing E toward optimum level of exploitation (Eopt) for the underexploited C. carpio and by increasing the size at first capture (Lc) toward the Lopt, range for all target species. PMID- 26666132 TI - [Home range of Aspidoscelis cozumela (Squamata: Teiidae): a parthenogenetic lizard microendemic to Cozumel Island, Mexico]. AB - Home range is defined as the area within which an individual moves to acquire resources necessary to increase their fitness and may vary inter and intra specifically with biotic and abiotic factors. This study details the home range of the parthenogenic lizard, Aspidoscelis cozumela, an active forager microendemic to Cozumel Island, Mexico, with high preference for open sand beaches. The home range of A. cozumela was compared with other species of Aspidoscelis (gonochoric and parthenogenetic) and other lizards that occupy coastal habitats. Furthermore, the biotic and abiotic factors that may influence home range were analyzed. This study was conducted in the beach located on the East side of the island (area of 4,000 M2) that is composed primarily of halophyte vegetation with high levels of sunlight. From 1999 to 2001, nine samples were taken which included the dry, rainy, "nortes", and breeding seasons. During each sampling, capture-mark-recapture techniques were conducted and the date, time of day, and snout-vent length (SVL) were recorded to the nearest millimeter. Individuals were located in the study area using a bi-coordinate reference using 10 x 10 m subdivisions of the habitat. Home range and home range overlap were calculated using the convex polygon method in McPaal and home range/SVL correlation was tested using Pearson's correlation. To calculate females home range, three or more recaptures were considered. A total of 20 home ranges that averaged 45.1 +/- 14.0 m2 were obtained and no correlation between SVL and home range size was detected (p = 0.9229, n = 20). However, removing individuals with outlier home ranges (females with home ranges > 100 m2, n = 2) resulted in a positive correlation with SVL (r = 0.61, p = 0.0072, n = 18). A 22.9 +/- 5.7% overlap in home range was also detected. The small home range of A. cozumela represents the smallest home range within the Aspidoscelis genus recorded to date (including both parthenogenetic and gonochoric species) and contrasts the theoretical predictions of broad home ranges for widely foraging species. Thermoregulatory benefits and a high population density may explain the small home range of A. cozumela. Although this species is highly adapted to the environmental conditions present on the open sand beaches, anthropogenic effects on these habitats by the development of tourism infrastructure may jeopardize their existence on Cozumel Island. PMID- 26666133 TI - [Distribution patterns of wild felids (Carnivora: Felidae) in the dry tropics of Central-Western Mexico]. AB - The Michoacan state is characterized by the existence of important environmental heterogeneity in terms of climate, topography and types of vegetation, which includes the worldwide endangered tropical dry forest. Some reports indicating the presence of the six species of felids occurring in Mexico in this region have been made; however, evidence to support these reports is scant, and filling this lack of information is particularly critical in the case of threatened species or habitats. The aim of this study was to systematize and analyze data distribution patterns of felids in the state of Michoacan, in the Central-Western Mexico. We conducted a review of literature and databases to compile species presence records in the study region. Moreover, we analyzed data obtained from ten years of field work conducted in the region, in which complementary methods (detection of direct and indirect evidence of species occurrence along transects, camera trapping and interviews to local people) were applied to detect the presence of felid species. We compiled a total of 29 presence records of felids in the region from our review. Additionally, field work, which accumulated 1,107.5 km of walked transects, and 8 699 camera-trap days, produced 672 records of species presence. Lynx rufus was the species with the lowest number of records and the most restricted distribution. In contrast, the species with the greatest number of records was Leoparduspardalis (n = 343). In general, 89% of felids records occurred below 1,000 masl. Overall mean annual temperature of presence records was 24 degrees C and mean annual precipitation was 1,040 mm. The species whose presence records showed the most distinctive pattern, in terms of temperature and precipitation associated, was L. rufus (15.8 +/- 1.3 degrees C and 941 +/- 171 mm). Results of a cluster analysis showed that areas supporting different combinations of eco-regions and types of vegetation could be grouped in five clusters having different assemblages of felid species and camera-trapping records. This study results useful to garner a more comprehensive view of the distribution patterns of felids in a region with important environmental contrasts and subjected to an increased human pressure. Moreover, this study provides insights that further our understanding of the relationship between environmental variables and felid distribution patterns which may have an impact for conservation and management strategies at the local and regional levels. PMID- 26666134 TI - [Population estimates and conservation of felids (Carnivora: Felidae) in Northern Quintana Roo, Mexico]. AB - Wildlife density estimates provide an idea of the current state of populations, and in some cases, reflect the conservation status of ecosystems, essential aspects for effective management actions. In Mexico, several regions have been identified as high priority areas for the conservation of species that have some level of risk, like the Yucatan Peninsula (YP), where the country has the largest population of jaguars. However, little is known about the current status of threatened and endangered felids, which coexist in the Northeastern portion of the Peninsula. Our objective was to estimate the wild cats' density population over time at El Eden Ecological Reserve (EEER) and its surrounding areas. Camera trap surveys over four years (2008, 2010, 2011 and 2012) were conducted, and data were obtained with the use of capture-recapture models for closed populations (CAPTURE + MMDM or 1/2 MMDM), and the spatially explicit capture-recapture model (SPACECAP). The species studied were jaguar (Panthera onca), puma (Puma concolor), ocelot (Leopardus pardalis), jaguarundi (Puma yaguaroundi) and margay (Leopardus wiedii). Capture frequency was obtained for all five species and the density for three (individuals/100km2). The density estimated with The Mean Maximum Distance Moved (MMDM), CAPTURE, ranged from 1.2 to 2.6 for jaguars, from 1.7 to 4.3 for pumas and from 1.4 to 13.8 for ocelots. The density estimates in SPACECAP ranged from 0.7 to 3.6 for jaguars, from 1.8 to 5.2 for pumas and 2.1 to 5.1 for ocelots. Spatially explicit capture recapture (SECR) methods in SPACECAP were less likely to overestimate densities, making it a useful tool in the planning and decision making process for the conservation of these species. The Northeastern portion of the Yucatan Peninsula maintains high populations of cats, the EEER and its surrounding areas are valuable sites for the conservation of this group of predators. Rev. Biol. PMID- 26666135 TI - Impact of jaguar Panthera onca (Carnivora: Felidae) predation on marine turtle populations in Tortuguero, Caribbean coast of Costa Rica. AB - Little is known about the effects of jaguars on the population of marine turtles nesting in Tortuguero National Park, Costa Rica. This study assessed jaguar predation impact on three species of marine turtles (Chelonia mydas, Dermochelys coriacea and Eretmochelys imbricata) that nest in Tortuguero beach. Jaguar predation data was obtained by using two methodologies, literature review (historical records prior the year 2005) and weekly surveys along the 29 km stretch of beach during the period 2005-2013. Our results indicated that jaguar predation has increased from one marine turtle in 1981 to 198 in 2013. Jaguars consumed annually an average of 120 (SD = 45) and 2 (SD = 3) green turtles and leatherbacks in Tortuguero beach, respectively. Based on our results we concluded that jaguars do not represent a threat to the population of green turtles that nest in Tortuguero beach, and it is not the main cause for population decline for leatherbacks and hawksbills. Future research should focus on continuing to monitor this predator-prey relationship as well as the factors that influence it so the proper management decisions can be taken. PMID- 26666136 TI - Floristic similarity and dispersal syndromes in a rocky outcrop in semi-arid Northeastern Brazil. AB - Floristic studies provide valuable information on species richness in a region, and are particularly important if these areas belong to less studied environments, such as rocky outcrops, that may increase our knowledge. An important aspect for species colonization includes the mechanisms of diaspores dispersal in each community; these are essential to understand its structure, dynamics, and the regeneration process, and constitute an important tool for conservation. We developed a floristic survey on a granite-gneiss outcrop with the objective to increase the knowledge on plant diversity, through a floristic similarity analysis and detection of dispersal syndromes of sampled species, in a semi-arid region of Brazil. The fieldwork included collection and observation of the botanical material in loco during a period of 12 months. A total of 161 species belonging to 127 genera and 50 families of angiosperms were recorded. Fabaceae, Asteraceae and Convolvulaceae were the most representative families in number of species. Allophylus quercifolius (Mart.) Radlk. (Capparaceae) and Lafoensia pacari A. St.-Hil. (Lythraceae) represented new records for the State of Paraiba. The autochoric syndrome was the most representative, with 51.5 % of the recorded species; the anemochory was the second most representative syndrome with 26.7 % of the species; and finally the zoochory, representing 22.3 % of the species. The floristic similarity dendrogram showed the formation of three well defined groups, whose area with the highest value (J = 33.2) is located in a Caatinga region called Cariri Paraibano, while the lowest value observed (J = 5.2), occurred in a settled area in two geomorphological units, a crystalline complex and a plateau region. These results may be due to the varying topographic conditions and edaphic heterogeneity arising from the specific geological formation of the region. These results yet demonstrate that, in rocky outcrops, abiotic syndromes represent an effective dispersion of its diaspores, favoring plant specie's colonization dynamics. PMID- 26666137 TI - [Loss of pubescence and their physiological effects on endangered rosette Espeletia paipana (Asteraceae), Boyaca-Colombia]. AB - Espeletia paipana is an endangered giant caulescent rosette endemic to (Asteraceae), Boyacdi-Colombia. Espelelia paipana is an endangered giant caulescent rosette endemic to Boyaca department. In order to establish whether a plant disease, characterized by the loss of leaf pubescence (PPF) and attributed to the pathogenic action of endophytic microorganisms, is the cause of the increasing mortality of population, the physiological performance of the species was evaluated with and without PPF. The incidence (% leaves affected in each of the 27 individuals in the current population) and severity (% leaf area affected on 135 leaves) of the PPF were monitored over a period of nine months, in three topographic zones of different heights. During four consecutive days in both dry and wet season, physiological parameters as chlorophyll content index (ICC), stomatal conductance (Gs) and leaf temperature (Tfol) were measured in healthy and affected leaves. The study was complemented with isolations and pathogenicity tests to identify the causal agent of the PPF. Overall, although the disease incidence in E. paipana was constant over time, the severity progressed surpassing 60 % of the leaf area. The increasing of severity in the upper side of leaves was attributed to the photo-oxidative effect of high radiation between 11:00 h and 14:00 h of the day. The reduction of functional leaf area because of the PPF, led to low Gs with serious implications for carbon fixation and thus limiting growth and biomass renewal. The effect of season in Tfol varied according to the topographic zone, while the ICC did not present a defined pattern with respect to the PPF; its low values could be associated with the production of other pigments. Finally, although it is not possible to ensure that Botrytis sp. is the causative of the loss of leaf pubescence, it is postulated as the most probably causal agent due to its high representativeness in the isolates and its infectious potential during the pathogenicity tests. In general, the reduction of healthy leaf biomass and decrease of physiological performance suggest that PPF affect negatively the survival of E. paipana, which means that the use of biological controllers could be a strategy to mitigate its effect on the population. PMID- 26666138 TI - Morphotype-based characterization of arbuscular mycorrhizal fungal communities in a restored tropical dry forest, Margarita island-Venezuela. AB - The mycorrhizal component of revegetated areas after ecological restoration or rehabilitation in arid and semiarid tropical areas has been scarcely assessed, particularly those made after mining disturbance. We evaluated and compared the presence of arbuscular mycorrhizal fungi of a small area of restored tropical dry forest destroyed by sand extraction, with a non-restored area of similar age, at the peninsula of Macanao, Margarita Island (Venezuela). Our study was undertaken in 2009, four years after planting, and the mycorrhizal status was evaluated in four restored plots (8 x 12.5 m) (two were previously treated with hydrogel (R2 and R2'), and two were left untreated (R1 and R1'), and four non-restored plots of similar size (NR1 and NR1' with graminoid physiognomy with some scattered shrubs; and NR2 and NR2', with a more species rich plant community). Apparently the restoration management promoted higher arbuscular mycorrhizal fungi (AMF) species richness and diversity, particularly in restored soils where the hydrogel was added (R2 treatment). Soil of the NRI treatment (with a higher herbaceous component) showed the highest spore density, compared to samples of soils under the other treatments. Considering species composition, Claroideoglomus etunicatum and Rhizophagus intraradices were found in all treatments; besides, Diversispora spurca and Funnefformis geosporum were only found in non-restored plots, while members of the Gigasporaceae (a family associated with little disturbed sites) were commonly observed in the plots with restored soils. Mycorrhizal colonization was similar in the restored and non-restored areas, being a less sensitive indicator of the ecosystem recovery. The trend of higher richness and diversity of AMF in the restored plot with hydrogel suggests that this management strategy contributes to accelerate the natural regeneration in those ecosystems where water plays an essential role. PMID- 26666139 TI - [Morphologic and molecular characterization of Phomopsis longicolla(teleomorph unknown: Diaporthales) from tempered and subtropical regions of Argentina]. AB - Diaporthe (teleomorpho)-Phomopsis - (anamorph) (DP) is a fungal group of great genetic diversity with over 900 species associated to a wide host range that includes cultivated and uncultivated species, forest, fruit trees and weeds. DP isolates are hemibiotrophs and have different sources of primary inoculum as stubble and seeds to restart cycles of parasitism - saprophytism. They colonize host tissues from early plant stages and establish different nutritional relationships, acting as endophytic and necrotrophic fungi. The plasticity of the Phomopsis genus has favored its expansion to different agro-ecosystems and various hosts constituting an epidemiological risk. The objective was to validate the identity and evaluate the biological relationships among 12 isolates of P longicolla and D. phaseolorum var. sojae (anamorph P phaseoli var. sojae) obtained in different tempered and subtropical agro-environments of Argentina, in order to analyze the variability and strategies for preserving fungal biodiversity. Macromorphological attributes (such as texture and color of colonies, stroma shape and distribution, pycnidia and perythecia shape and distribution) and micro-morphological characteristics (such as size and shape of conidia, asci and ascospores) allowed identifying three new isolates as P longicolla. A complementary molecular analysis was also made to overcome the limitations derived from the morphological analysis, thus the AFP.8413 isolate was finally identified as P longicolla. The molecular characterization was useful to identify the evaluated isolates and to group them in four taxa of the Diaporthe-Phomopsis complex: ten isolates were included in P. longicolla, one isolate was included in D. phaseolorum var. sojae (anamorph P. phaseoli var. sojae), one isolate was identified as D. phaseolorum var. caulivora and two isolates were included in D. phaseolorum var. meridionalis. The use of phenotipic and molecular tools have contributed to an accurate identification of P longicolla, and comprehension about the biological relationships (homo or heterothallic hibridizations) among D. phaseolorum varieties (P phaseoli) and species of Diaporthe-Phomopsis. This allowed also a better understanding of the mechanisms of fungic plasticity, to colonize and expand their host range and genetic variability, promoting thus their biodiversity conservation. Rev. Biol. Trop. 63 (3): 871-884. Epub 2015 September 01. PMID- 26666140 TI - [The mechanism of action of antidiabetic drugs]. PMID- 26666141 TI - [Clinical and pathophysiological features of Japanese patients with type 2 diabetes mellitus and their risk factors for diabetic complication]. AB - The pathophysiological backgrounds as well as clinical phenotypes of Japanese or East Asian patients with type 2 diabetes are quite different from those in Western countries. According to results of East Asian large-scale studies such as the Japan Diabetes Complications Study (JDCS), which is a representative cohort of Japanese patients with type 2 diabetes, Japanese patients had a much lower body mass index and lower incidence of coronary heart disease compared with Caucasian diabetic patients. Other differences between Japanese and Caucasian patients with type 2 diabetes could be found in risk factors such as fruit intake on retinopathy and significance of triglycerides, or the effects of moderate alcohol drinking on cardiovascular disease. These results demonstrated a necessity of ethnic group-specific risk evaluations and care of type 2 diabetes and its complications. PMID- 26666142 TI - [Significance of the regulation of hyperglucagonemia in type 2 diabetes mellitus]. AB - Abstract Generally, pancreatic beta-cell dysfunction and hypoinsulinemia have been known as the cause of development of hyperglycemia in diabetes mellitus. Pancreatic alpha-cell dysfunction, particularly hyperglucagonemia is also serious problem to increase hepatic glucose production in type 2 diabetes mellitus (T2DM). beta-cell mass decrement and alpha-cell mass increment in T2DM have been reported in many reports inclusive of our study. Those might be the background to the pancreatic cells dysfunction in T2DM. Glucagon secretion from alpha-cells could not be suppressed by insufficient insulin, and hyperglucagonemia has been worsening in T2DM. Incretin, particularly glucagon like peptide-1 (GLP-1) could control both alpha- and beta-cell dysfunction, via the decrease of glucagon and the increase of insulin respectively. We believe that incretin therapy(GLP-1 receptor agonists and DPP-4 inhibitors) is the best strategy to control hyperglucagonemia caused by alpha-cell dysfunction in T2DM. PMID- 26666143 TI - [Type 1 diabetes]. AB - Most type 1 diabetes is a chronic disease characterized by the body's inability to produce insulin due to an autoimmune destruction of pancreatic beta cells. Type 1 diabetes can be classified into 3 types according to the onset pattern of hyperglycemia; i.e., acute onset, slowly progressive and fulminant type 1 diabetes, and the diagnostic criterion for each type of diabetes has been recently established. Intensive insulin therapy by multiple daily injections or continuous subcutaneous insulin infusion is best for keeping blood sugar in tight control and recommended for most people with type 1 diabetes. In addition, carbohydrate counting is a recommended dietary strategy for achieving glycemic control in patients with type 1 diabetes. PMID- 26666144 TI - [Pathophysiology of type 2 diabetes mellitus]. AB - The development of type 2 diabetes is usually associated with a combination of pancreatic beta-cell dysfunction and insulin resistance in various insulin target tissues such as the liver, muscle and adipocytes. Normal beta-cells can compensate for insulin resistance by increasing insulin secretion or beta-cell mass, but insufficient compensation leads to the onset of glucose intolerance. Once hyperglycemia becomes apparent, beta-cell function gradually deteriorates and insulin resistance aggravates. This process is called "glucose toxicity". PMID- 26666145 TI - [Secondary diabetes]. AB - Secondary diabetes is diabetes that results as a consequence of another medication, endocrine disease or hereditary disease. Secondary diabetes is very broad and diverted category among diabetes. Clinically, pancreatic diabetes is one of the most popular secondary diabetes, which provides insulin deficiency following pancreatic diseases, such as pancreatitis and pancreatic cancer. Among endocrine diseases, Cushing's syndrome and acromegaly are typical endocrine disorders causing secondary diabetes. They mainly induce insulin resistance in early stage, however, insulin deficiency is also observed in advanced stage. Steroid is the most popular drug-induced secondary diabetes. Importantly, not only oral administered steroid but also cutaneous and inhalation steroid could induce hyperglycemia. Major hereditary diabetes are MODY and mitochondrial diabetes. Concerning secondary diabetes, careful medical examination is required. PMID- 26666146 TI - [Gestational diabetes mellitus]. AB - Five years have passed since the criteria of gestational diabetes mellitus (GDM) were revised. Under these new criteria, prevalence of GDM has increased from 2-3% to 8-10%. This increase raises many arguments especially about cost effectiveness of managing newly diagnosed mild GDM showing only one abnormal value in 75 gOGTT. No evidence is yet to be found. But in our everyday experience, we find out few poor perinatal outcome with mild GDM mothers who are treated only with diet regimen to control their body weight. Considering later development to type 2 diabetes with these mild GDM mothers, they show no obvious difference from non GDM mothers in the retrospective study. PMID- 26666147 TI - [Childhood and adolescent diabetes in Japan]. AB - The glycemic control in Japanese children and adolescents with type 1 diabetes has been improved with emphasis on increase in target level of HbA1c<7.5% and decrease in risk level >= 9%. It may be due to increase the basal-bolus insulin therapy in almost all patients across ages, especially pubertal ages, following the use of rapid acting insulin analogues and long-acting analogues. Regarding to type 2 diabetes, little improvement has been observed because of the lack of enough skill to guide. The interruption of therapy or visiting medical resources may be a big burden. Monogenic diabetes has been more frequently found from previously diagnosed type 1B diabetes and type 2 diabetes. MODY genes can be noticed in children from urine-screening program, with the history of low-birth weight, even not having family history of diabetes and so on. PMID- 26666148 TI - [Diabetes in older adults]. AB - In the therapeutic approach to elderly diabetic patients, it is necessary to consider that diabetes is one aspect of geriatric syndrome, and individualizing targets of treatments are needed based on the presence of frail, dementia, and activity of daily living. Because of decreased physiological functions along with aging, older patients are prone to cause hypoglycemia by drug therapy. Thus, proper using of drugs for older patients are important. In several countries, some clinical practice guidelines for older diabetes have been made. In this year, The Japan Geriatrics Society and The Japan Diabetes Society collaborate and start to prepare clinical practice guideline for individualizing targets of older diabetes' treatments. Overmedication for older diabetes without authority has to be avoided, because it leads to negative influence on quality of older patients' lives. PMID- 26666149 TI - [Diabetic retinopathy]. AB - Diabetic retinopathy is a major cause of vision loss in Japan. Recent progress in the treatments of diabetic retinopathy includes the use of pattern scan laser photocoagulation, subthreshold micropulse laser photocoagulation, and micro incision vitreous surgery with chandelier illumination and wide-angle viewing system. The use of triamcinolone, indocyanine green or brilliant blue G, which are used to visualize the vitreous and the internal limiting membrane, respectively, has greatly facilitated vitreous surgery. As for intraocular drug therapy, antivascular endothelial growth factor agents are now available for diabetic retinopathy, useful not only for treating diabetic macular edema, but also for controlling bleeding during vitreous surgery and for temporarily suppressing the symptoms of proliferative diabetic retinopathy. PMID- 26666150 TI - [Diagnosis and management of diabetic nephropathy]. AB - Diabetic nephropathy(DN) is the most common cause of chronic kidney disease, leading to end-stage renal disease (ESRD) and cardiovascular disease (CVD). The overall number of patients with DN will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. The detection of albuminuria is most important for diagnosis of early stage of DN, and also estimated glomerular filtration rate (eGFR) should be assessed, because both albuminuria and reduction of GFR are recognized as the independent risk factor for progression of ESRD and initiation of CVD, respectively. Based on landmark clinical trials, both DN and CVD have become preventable by controlling conventional factors, including hyperglycemia targeting HbA1c<7.0%, hypertenstion using renin angiotensin system inhibitors, dyslipidemia using statins or fibrates, and multifactorial treatment. PMID- 26666151 TI - [Diabetic neuropathy]. AB - Diagnostic criteria of diabetic neuropathy that can be easily used at bedsides and have international consensus have not been established. The most important therapeutic strategy is to maintain strict glycemic control. In addition, treatment with an aldose reductase inhibitor that is innovated from the viewpoint of the pathogenesis of diabetic neuropathy would be useful for preventing the progression of diabetic neuropathy. For painful diabetic neuropathy, pregabalin and duloxetine effectively relieve the pain, and contribute to the improvement of the quality of life. PMID- 26666152 TI - [Cardiovascular complications of diabetes]. AB - Several lines of epidemical evidence have shown that type 2 diabetes is the most important risk factor for cardiovascular diseases (CVD). It has been shown that the risk of primary prevention of CVD in patients with diabetes is equal to that of the secondary prevention in general population. In this manuscript, recent reports on the cardiac tests to detect the cardiovascular lesions will be reviewed. The data suggest that MDCT is a promising test even in the patients with diabetes. Furthermore, recent evidence of the treatment of diabetes with insulin or the drugs available recently such as DPP-4 inhibitors and SGLT-2 inhibitors will be reviewed. PMID- 26666153 TI - [Management of stroke in patients with diabetes mellitus]. AB - Diabetes mellitus is an independent risk factor for ischemic stroke. Medical interview, physical, neurological, and radiological examination are performed for diagnosis of stroke. CT, MRI, MRA, CT angiography, and carotid ultrasonography are used for classification of type of ischemic stroke. Immediate treatment using such as rt-PA or endovascular therapy improves the prognosis. Antiplatelet therapy is recommended for purposes of risk reduction of recurrent stroke, but blood sugar control is uncertain. PMID- 26666154 TI - [Obesity disease with diabetes mellitus]. AB - Obesity has been increasing not only in Japan but also in both developed and developing countries. Mean body mass index of Japanese patients with type 2 diabetes has been increasing, and it reached 25.0 in 2013. If body weight decreases more than 3% of initial body weight in patients with metabolic syndrome, not only glucose metabolism but also dyslipidemia and hypertension improve. To reduce the excess body weight, behavior therapy, calorie restriction, and exercise are necessary. The next strategies are drugs including mazindol, glucose-like peptide-1 receptor agonist and sodium-dependent glucose cotransporter 2 inhibitor, and bariatric surgery. Because it is often difficult to reduce body weight using only present non-invasive therapies, clarification of appetite mechanisms and development of novel anti-obesity drugs with few side effects are needed. PMID- 26666155 TI - [Hypertensive management of the diabetic patients]. AB - Cardiovascular disease risk of hypertensive patients with diabetes mellitus is high. Therefore, more stringent blood pressure control has been needed for antihypertensive treatment by blockades of renin angiotensin system. However, many patients with diabetes and hypertension already have vascular lesions. When starting the antihypertensive medication in these patients, it is necessary to consider the existence of cerebrovascular disorder, coronary artery disease, and renal artery stenosis. PMID- 26666156 TI - [Dyslipidemia in diabetes mellitus: diagnosis and treatment]. AB - Dyslipidemia in diabetes mellitus is a secondary change in hyperglycemia. Even if hyperlipidemia was not present, dyslipidemia will be present, especially as the increase of remnant. Usually this dyslipidemia is improved by a good control of hyperglycemia. In the pathogenesis the various factors relate to the lipid/lipoprotein metabolism, by insulin action (hyperinsulinemia or insulinopenia), adipokines, or hyperglycemia itself. The every changes of lipoprotein metabolism could be occurred in diabetes mellitus, and those are related to the increase of atherogenic lipoproteins. We should recognize the mechanism of lipids/lipoprotein metabolism in diabetes mellitus and approach to prevent the atherosclerotic diseases in diabetes. PMID- 26666157 TI - [Infection complicated with diabetes mellitus]. AB - Patients with diabetes mellitus are believed to be suspected to be immunocompromized hosts. Many reports have pointed out that diabetic patients are susceptible to certain infections such as surgical site infections, malignant otitis externa, mucormycosis, and necrotizing fasciitis. But their etiology seems to be non-uniform, heterogenous and individualized. Above all, obesity-related infections are also increasing accompanied with the recent rising incidence of obesity. Further studies should be addressed about the relationships between infections and diabetes which include the factors of body mass index, life style, degree of diabetes complications, and poor glycemic control duration. They could live a normal life the same as healthy subjects if good glycemic control is achieved without hypoglycemia. PMID- 26666158 TI - [SGLT2 inhibitor]. AB - SGLT2 is a glucose transporter which plays an important role for reabsorption of urinary glucose depending on the sodium concentration gradient. SGLT2 is mainly present in apical site of S1 segment of renal proximal tubule and accounts for approximately 90% of total urinary glucose reabsorption. SLC5a2, which codes SGLT2, is also known as the causative gene of familial renal glucosuria. SGLT2 inhibitors are attracting attention as newly developed oral anti-diabetic agents which improve glucose intolerance and also have an anti-obese effect by promoting urinary glucose excretion (UGE), which is a different pharmacological effect from other conventional anti-diabetic agents. In this review, we will discuss the effect of SGLT2 inhibitor on the regulation of glucose and lipid metabolism in type 2 diabetes. PMID- 26666159 TI - [Once-weekly DPP-4 inhibitor]. AB - Trelagliptin is the first once-weekly dipeptidyl peptidase-4(DPP-4) inhibitor in the world. Trelagliptin inhibits DPP-4 activity with lower drug concentration compared with other once- (or twice-) daily DPP-4 inhibitors in in vitro study. More than 70 % of DPP-4 activity is inhibited even 1 week after administration of trelagliptin administration in human study. 24-week trelagliptin monotherapy improved HbA1c(-0.33%) and fasting plasma glucose levels in Japanese patients with type 2 diabetes. Trelagliptin did not affect body weight and frequency of hypoglycemic events in this study. 52-week monotherapy and add-on therapy of trelagliptin also improved HbA1c levels without body weight gain and severe hypoglycemia. Therefore, trelagliptin has high efficacy and safety on glucose control in Japanese patients with type 2 diabetes. PMID- 26666160 TI - [Future of ultra long-acting insulin analogues]. AB - Optimal insulin therapy should mimic endogenous insulin secretion in healthy subjects and maintain normal glycemic control. Short- or rapid-acting insulin is used to mimic the response of insulin secretion after meal. Basal insulin restrains hepatic glucose production in fasting state, and should be mimicked by neutral protamine Hagedorn (NPH) or long-acting insulin. Long-acting basal insulin analogues offer some advantage over the NPH insulin in terms of less glycemic variability when used once daily. Various scientific associations recommend once-daily basal insulin when starting insulin therapy; therefore, long acting basal insulin analogues play important part of continual and optimal insulin therapy. In this article, we review long-acting basal insulin analogues currently available in Japan and new basal insulin in research and development phase. PMID- 26666161 TI - [The trend of new drug development for the treatment of diabetes mellitus]. AB - The trend of new drug development in the field of diabetes mellitus is overviewed. The hypoglycemic drugs such as glucagon receptor antagonists, glucokinase activators, and GPR agonists and oral medication of GLP-1 receptor agonist are under phase 2 trial in Japan. As for therapeutic medicines for diabetic nephropathy, atrasentan as an endothelin A receptor antagonist is in phase 3 trial, and bardoxolone methyl as Nrf2 activator in phase 2 in Japan. Canagliflozin, a SGLT2 inhibitor, is in phase 3 study to obtain new indication of diabetic nephropathy. An environment surrounding development of therapeutic medicines for diabetes has been tough since FDA guidance in 2008. PMID- 26666162 TI - [Pancreatic islet transplantation]. AB - Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes with severe hypoglycemic unawareness. A major benefit of islet transplantation is that it does not require major surgery. Islet transplants, though significantly improving, are still mostly done on an experimental basis. In Japan, phase II clinical trial to confirm the safety and efficacy of islet transplantation has been in progress. The induction of the regenerative medicine approach is also expected to accelerate the growth of islet transplantation. In this review, we give an outline about a summary of islet transplantation in Japan and the future prospects based on the latest findings. PMID- 26666163 TI - [The present status and perspective of pancreas transplantation in Japan]. AB - Two hundred and ten cases of pancreas transplantation from deceased and non-heart beating donors have been performed in 17 institutions in Japan until the end of 2014 since April, 2000. The following donor- and recipient-related factors were analyzed; i.e., age and gender of donor and recipient, cause of death, histories of diabetes and dialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and survival rates of patient and graft. The patient survivals were 96.5%, 95.8%, and 95.8% while the pancreas graft survivals were 84.7%, 77.0%, and 70.4% at 1 year, 3 years and 5 years posttransplantation, respectively. In spite of donor poor conditions which were mostly marginal (67.1%) in Japan, the outcome of pancreas transplants was considered to be comparable to that of the US and Europe. PMID- 26666164 TI - [Generation of three-dimensional pancreatic tissue from human induced pluripotent stem cells]. AB - The functional cells or tissues derived from human induced pluripotent stem cells (iPSCs) make it possible to overcome with the insufficiency of cell sources for regenerative medicine, to investigate the precise mechanism of human organogenesis and disease, and to develop the new drugs. Especially for type 1 diabetes, making mature pancreatic beta cells from human iPSCs might have a good opportunity of regenerative medicine. However, so far in vitro, producing the fully maturated pancreatic beta cells is not achieved. Here we review the previous reports and discuss the possibility and validity of our strategy for making mature pancreatic beta cell with three-dimensional culture of pancreatic organoid derived from human iPSCs. PMID- 26666165 TI - [Recent trends on clinical development of oral insulin delivery systems]. AB - Great effort for developing effective needle-free insulin delivery technology, especially oral delivery, has been continued in worldwide, indeed, from the era of insulin discovered. Oral administration of insulin would offer not only the potential for improved patient compliance but also improved safety/efficacy in certain instances. Much effort for developing noninvasive delivery systems of insulin has been done, and recently, several promising insulin oral formulations are entered into clinical trials. Delivering insulin in orally was major challenge, but its realization is surely approaching. This review provides an update on recent approaches that have shown promise in insulin oral delivery systems. In addition, the progress of basic research in noninvasive delivery system research for biopharmaceuticals is discussed. PMID- 26666166 TI - [Empowerment approach to the management of comorbid diabetes and cancer]. AB - Diabetes mellitus is a frequent comorbidity of cancer patients. Recent data show that diabetes may negatively impact both cancer risks and outcomes of treatment. It is important to identify patients at risk for complications that arise from cancer treatment in the setting of pre-existing diabetes. Additionally, underlying hyperglycemia or hidden diabetes in a patient undergoing cancer treatment such as chemotherapy including steroid administration and total parenteral nutrition should be identified and managed. Strategies for monitoring and managing hyperglycemia during the course of cancer treatment will be reviewed. The role of interdisciplinary care and empowerment approach is crucial to supporting patients and their families as they manage through the challenges of facing two life-threatening diseases. PMID- 26666167 TI - [Camurati-Engelmann disease]. AB - Camurati-Engelmann disease (CAEND, OMIM 131300) is a rare autosomal dominant, progressive diaphyseal dysplasia, which is characterized by hyperosteosis and sclerosis of the diaphyses of long bones. Estimated number of patients with CAEND in Japan is approximately 50-60 by our epidemiological survey. We have reported that domain-specific mutations in transforming growth factor-beta1 gene(TGFB1) cause CAEND. Mutations in latency associated peptide(LAP) domain of TGF-beta1 destabilize the complex and may hyperactivate TGF signal pathway. We tried to establish CAEND model mice by gene-targeting, but could not because of spermatogenesis defects in chimera mice. We also failed using CRISPR/Cas9 system. Alternatively, we established CAEND patient-derived iPS cells, and are advancing research with them to develop novel therapeutic agents for CAEND. PMID- 26666168 TI - Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections. AB - BACKGROUND: Identification of coagulase-negative staphylococci (CoNS) as nosocomial pathogens or contaminants is significant for microbiologists and clinicians. This study aimed to determine the frequency of isolation and antimicrobial resistance patterns of CoNS isolates from nosocomial bloodstream infections (BSIs) and to identify risk factors associated with true bacteremia caused by these emerging pathogens in a Saudi tertiary care hospital. METHODS: All CoNS-positive cultures from inpatients were identified using the standard methods during a 10-month period. Antimicrobial susceptibility testing was done using the reference broth microdilution method. RESULTS: A total of 208 isolates were identified; of these 75 (32.2%) were considered infection associated, and 133 (67.8%) were considered contamination. S. epidermidis accounted for 34.7% of bacteremia cases, followed by S. hominis (21.3%), S. haemolyticus (16%), and S. saprophyticus (12%). Central venous catheters (p <= 0.0001), prior antibiotic therapy (p <= 0.0001), the occurrence of more than one positive blood culture (p <= 0.0001), and intensive care unit (ICU) admission (p = 0.007) were all independently associated with CoNS bacteremia. Overall, all isolates were highly resistant to penicillin (94.7%), oxacillin (90.7%), and erythromycin (85.3%). The rates of susceptibility to vancomycin, daptomycin, and teicoplanin were 98.7%, 98.7%, and 93.3%, respectively. CONCLUSIONS: Our results further highlight that accurate identification and susceptibility testing of CoNS isolates from nosocomial BSIs are crucial to minimize excessive antibiotic use and unnecessary catheter removal. In addition, daptomycin may be an efficient alternative therapeutic option for CoNS resistant to oxacillin and other commonly used antibiotics. PMID- 26666169 TI - Rare-Earth-Free High-Efficiency Narrow-Band Red-Emitting Mg3Ga2GeO8:Mn4+ Phosphor Excited by Near-UV Light for White-Light-Emitting Diodes. AB - A series of novel red emission Mg3Ga2GeO8 (MGG):Mn(4+) phosphors under near-UV (NUV) excitation are synthesized successfully by traditional high-temperature solid-state reaction. The structure of Mg3Ga2GeO8 is investigated by high resolution transmission electron microscopy, scanning electron microscopy, and powder X-ray diffraction (XRD) Rietveld refinement. It has one octahedral site and one tetrahedral site in the crystal structure. According to XRD and photoluminescence (PL) property analysis, Mn(4+) can occupy an octahedral (Mg(2+)/Ga(3+)) site. The PL properties are investigated by diffuse-reflectance, emission, excitation, and temperature-dependent spectroscopy and decay curves. It can emit red light peaking at 659 nm under NUV excitation. The critical quenching concentration of Mn(4+) was about 0.5 mol %. The concentration quenching mechanism could be a d-d interaction for the Mn(4+) center. The CIE chromaticity coordinates and full-width at half-maximum are (0.295, 0.677) and 24 nm, respectively. It demonstrated that MGG:Mn(4+) has high color purity. The PL intensity of MGG:0.5% Mn(4+) drops to 72% when the temperature is raised up to 150 degrees C. Furthermore, MGG:0.5% Mn(4+) exhibits outstanding quantum efficiency (64.7%). By tuning of the weight ratio of blue, green, and red phosphors, the fabricated white-light-emitting diodes using a 405 nm GaN NUV chip combined with a blend of blue phosphor BAM:Eu(2+), green phosphor Sr2SiO4:Eu(2+), and red-emitting phosphor MGG:Mn(4+) driven by 40 mA current can get white light with chromaticity coordinates (0.316, 0.375) and CCT = 3340 K. This demonstrates that MGG:Mn(4+) is a potential red phosphor matching NUV LED chips to get white light. PMID- 26666170 TI - Asthma insights from Jordan: cross-sectional observational study. AB - OBJECTIVE: The burden of uncontrolled asthma on patients in Jordan is largely unknown. This study assessed different aspects of asthma clinical features: the level of asthma control, its correlation with quality of life, and possible predictors of asthma control. METHODS: Face-to-face interviews with asthmatic patients (>=16 years old) in north Jordan from 2013 to 2014 were conducted. Outcomes measures were assessed using the asthma control test (ACT), the mini asthma quality of life questionnaire (mini-AQLQ), and the Generic health-related quality of life (EQ-5D). The relationship between asthma control and quality of life was examined using Spearman's correlation coefficient. Predictors of asthma control were determined using multivariable logistic regression adjusted for confounders. RESULTS: A total of 255 patients were recruited (mean age 45.16 years, 74.5% female). Approximately one-third of subjects (30.6%; n = 78) had controlled asthma (ACT >= 20). A strong correlation between asthma control and both mini-AQLQ and EQ-5D scores was identified (p < 0.001). Subjects who required to step-up treatment (OR = 0.12, 95% CI: 0.02-0.63, p = 0.01) and with acute asthma exacerbation (OR = 0.32, 95% CI: 0.18-0.58, p < 0.001) were independently associated with poor asthma control. CONCLUSIONS: Most of the recruited patients have not achieved optimal asthma control and was associated with low quality of life. The study highlights that even in low-income countries, a simple assessment tool such as the ACT can be utilized to screen and categorize asthma control. This approach would facilitate a better treatment plan and eventually improve asthma control and quality of life in asthma patients. PMID- 26666171 TI - Selective cytotoxic eremophilane-type sesquiterpenes from Penicillium citreonigrum. AB - One new eremophilane-type sesquiterpene (1, citreopenin) was isolated from Penicillium citreonigrum (HQ738282), and the structure was elucidated by a combination of spectroscopic data interpretation and single-crystal X-ray diffraction analysis using Cu Kalpha radiation (CCDC 1030588). Compound 1 showed weak activity against KB-VIN (IC50 = 11.0 +/- 0.156 MUM), while the known compound 3 exhibited selective cytotoxicity against MDA-MB-231 triple-negative breast cancer (TNBC) (IC50 = 5.42 +/- 0.167 MUM). PMID- 26666172 TI - Correction: Analysis of computational models for an accurate study of electronic excitations in GFP. AB - Correction for 'Analysis of computational models for an accurate study of electronic excitations in GFP' by Tobias Schwabe et al., Phys. Chem. Chem. Phys., 2015, 17, 2582-2588. PMID- 26666174 TI - The contribution of visual processing to academic achievement in adolescents born extremely preterm or extremely low birth weight. AB - Children born extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) have more academic deficiencies than their term-born peers, which may be due to problems with visual processing. The aim of this study is to determine (1) if visual processing is related to poor academic outcomes in EP/ELBW adolescents, and (2) how much of the variance in academic achievement in EP/ELBW adolescents is explained by visual processing ability after controlling for perinatal risk factors and other known contributors to academic performance, particularly attention and working memory. A geographically determined cohort of 228 surviving EP/ELBW adolescents (mean age 17 years) was studied. The relationships between measures of visual processing (visual acuity, binocular stereopsis, eye convergence, and visual perception) and academic achievement were explored within the EP/ELBW group. Analyses were repeated controlling for perinatal and social risk, and measures of attention and working memory. It was found that visual acuity, convergence and visual perception are related to scores for academic achievement on univariable regression analyses. After controlling for potential confounds (perinatal and social risk, working memory and attention), visual acuity, convergence and visual perception remained associated with reading and math computation, but only convergence and visual perception are related to spelling. The additional variance explained by visual processing is up to 6.6% for reading, 2.7% for spelling, and 2.2% for math computation. None of the visual processing variables or visual motor integration are associated with handwriting on multivariable analysis. Working memory is generally a stronger predictor of reading, spelling, and math computation than visual processing. It was concluded that visual processing difficulties are significantly related to academic outcomes in EP/ELBW adolescents; therefore, specific attention should be paid to academic remediation strategies incorporating the management of working memory and visual processing in EP/ELBW children. PMID- 26666173 TI - MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy. AB - BACKGROUND: Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER(+)) breast cancers. However, the development of endocrine resistance is the impediment for successful treatment. We aimed to explore the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. METHODS: Experiments were performed in ER(+) and estrogen/TAM-sensitive MCF7 cells and antiestrogen resistant MCF7/LCC9 cells. The expression of miR-214 and uncoupling protein 2 (UCP2) was determined by RT-qPCR and Western blot in breast cancer cells and human breast cancer tissue specimens. Cell autophagy was examined by fluorescent probe monodansyl cadaverine (MDC) and GFP-LC3-II-positive punctate identified by confocal microscopy. Apoptotic cells were determined by Annexin V-FITC/PI staining. The potential regulatory target of miR-214 was determined by prediction tool, target protein expression and luciferase reporter assay. RESULTS: 4-OHT/FUL treatment resulted in induction of apoptosis as well as autophagy in breast cancer cells. Autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. MiR-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL induced apoptosis through inhibition of autophagy. Importantly, a negative correlation was established between miR-214 and UCP2 in human breast cancer tissue specimens assayed by RT-qPCR. UCP2 was identified to be a direct target of miR-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3K-Akt-mTOR pathway, thereby inducing autophagy by overexpression of UCP2. CONCLUSION: MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through inhibition of autophagy by targeting UCP2. MiR-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER(+) breast cancers. PMID- 26666175 TI - Population genetic analysis reveals cryptic sex in the phytopathogenic fungus Alternaria alternata. AB - Reproductive mode can impact population genetic dynamics and evolutionary landscape of plant pathogens as well as on disease epidemiology and management. In this study, we monitored the spatial dynamics and mating type idiomorphs in ~700 Alternaria alternata isolates sampled from the main potato production areas in China to infer the mating system of potato early blight. Consistent with the expectation of asexual species, identical genotypes were recovered from different locations separated by hundreds of kilometers of geographic distance and spanned across many years. However, high genotype diversity, equal MAT1-1 and MAT1-2 frequencies within and among populations, no genetic differentiation and phylogenetic association between two mating types, combined with random association amongst neutral markers in some field populations, suggested that sexual reproduction may also play an important role in the epidemics and evolution of the pathogen in at least half of the populations assayed despite the fact that no teleomorphs have been observed yet naturally or artificially. Our results indicated that A. alternata may adopt an epidemic mode of reproduction by combining many cycles of asexual propagation with fewer cycles of sexual reproduction, facilitating its adaptation to changing environments and making the disease management on potato fields even more difficult. PMID- 26666176 TI - Differential diagnosis of Brucella abortus by real-time PCR based on a single nucleotide polymorphisms. AB - To diagnose brucellosis effectively, many genus- and species-specific detection methods based on PCR have been developed. With conventional PCR assays, real-time PCR techniques have been developed as rapid diagnostic tools. Among them, real time PCR using hybridization probe (hybprobe) has been recommended for bacteria with high DNA homology among species, with which it is possible to make an accurate diagnosis by means of an amplification curve and melting peak analysis. A hybprobe for B. abortus was designed from a specific single-nucleotide polymorphism (SNP) on the fbaA gene. This probe only showed specific amplification of B. abortus from approximately the 14th cycle, given a melting peak at 69 degrees C. The sensitivity of real-time PCR was revealed to be 20 fg/ul by 10-fold DNA dilution, and the detection limit was 4 CFU in clinical samples. This real-time PCR showed greater sensitivity than that of conventional PCR and previous real-time PCR based on Taqman probe. Therefore, this new real time PCR assay could be helpful for differentiating B. abortus infection with rapidity and accuracy. PMID- 26666177 TI - The association of culling and death rate within 30 days after calving with productivity or reproductive performance in dairy herds in Fukuoka, Southern Japan. AB - The incidence of peripartum disorders in dairy herds negatively influences productivity and reproductive performance. Concrete data from local areas are helpful for explaining the importance of peripartum management to dairy farmers. This study was conducted to clarify the association of culling and death rate within 30 days after calving with productivity or reproductive performance in 179 dairy herds in Fukuoka, Southern Japan. A database was compiled from the records of the Livestock Improvement Association of Japan, the Dairy Cooperative Association and the Federation of Agricultural Mutual Relief Association. In this study, we created a comprehensive database of dairy farm production data for epidemiological analysis and used a general linear mixed model to analyze the association of culling and death rate within 30 days after calving with milk production or reproductive performance. The database can be used to describe, analyze and predict the risk of production. A cross-sectional analysis with contrasts was applied to investigate the association of cows served by AI/all cows, pregnant cows/cows served by AI, days open, milk yield and somatic cell counts with culling and death rate within 30 days after calving. The days open value significantly increased with increasing rate of culling and death within 30 days after calving (P for trend <0.001). No significant differences were found for the other comparisons. Our data suggest that proper feeding and management in the dry period may lead to improved postpartum reproductive performance in this dairy cow cohort. PMID- 26666179 TI - LRP5 associates with specific subsets of macrophages: Molecular and functional effects. AB - Innate and acquired immunity is involved in the progression of atherosclerosis. The molecular mechanisms ruling monocyte to macrophage (Mo) differentiation are not yet fully understood. Different subtypes of plaque macrophages that have differentiated from monocytes recruited from circulating blood, have been characterized based on surface epitopes. We have recently shown that LRP5, a member of the LDL receptor superfamily supporting Wnt signalling, has an important role in monocyte to macrophage differentiation. The aim of this study was to investigate whether the CD16- and CD16+ macrophage subsets found in human atherosclerotic plaques have a differential LRP5 expression/function and Wnt signalling potential. We show for the first time that LRP5 expression is significantly higher in human CD16+Mo derived from CD14(+)CD16(+) monocytes than in CD16-Mo macrophages derived from CD14(+)CD16(-) monocytes. LRP5 is not found in human healthy vessel or arterial intimal thickening but is found in advanced human atherosclerotic lesions co-localizing only with the CD16+Mo macrophage subset. LRP5 expressing macrophages infiltrate the deep layers of atherosclerotic plaques towards the intima-media boundaries showing increased migratory activity and higher phagocytic activity. The equivalent for human patrolling CD14(+)CD16(+) monocytes in mice, CD115(+)GR1(low) monocytes, also show an increased expression of LRP5. In summary, classical CD14(+)CD16(-)monocytes that differentiate into CD16-Mo do not express LRP5. Instead, human monocytes expressing LRP5 differentiate into CD16+Mo antiinflammatory macrophages. These antiinflammatory macrophages are found in advanced atherosclerotic human plaques. Thus LRP5 is a signature of the anti-inflammatory defensive phenotype of macrophages. PMID- 26666180 TI - Relative age effect and performance in the U16, U18 and U20 European Basketball Championships. AB - This study sought to determine the association of relative age and performance of young elite basketball players. The distribution of the birth dates, heights, positions, classification and performance of the male and female participants (n = 2395) of the U16, U18 and U20 European Basketball Championships were analysed. We found an over-representation of players born during the initial months of the year in all groups, with the relative age effect being more evident in players of the U16 and U18 groups, than of the U20 teams, particularly in male squads. Nevertheless, in the U20 championships, those teams that had the oldest players performed the best. In all championships, the oldest participants played more minutes. In addition, relatively older male players scored better in total points and in performance index rating when results were normalised to played time. This effect was not found for female players. Regarding playing position, different distributions of birth dates were observed due to each position's physical requirements. Thus, basketball coaches and managers should keep these results in mind when they select players because if not, they might subject players who are born towards the end of the year to a negative selection bias. PMID- 26666178 TI - Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development. AB - Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents (N = 90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co expression profile in prenatal frontal cortex (Bonferroni corrected p < 9.1 * 10( 3)), and in prenatal temporal and parietal regions (Bonferroni corrected p < 0.03). Also, four prenatal anatomical subregions (VCF, MFC, OFC and ITC) have shown significant enrichment of connectedness in co-expression networks. Moreover, four genes (LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. PMID- 26666181 TI - Bluetongue: Indian perspective. AB - Bluetongue (BT) is an insect borne (Culicoides) viral disease of small ruminants in India. While seroprevalence for BT is observed mostly in domestic and wild ruminant animals, the clinical form of disease and severe mortality is observed in sheep. Since the first report of BT in 1960s the country became endemic for the disease and most of the BT virus (BTV) serotypes (22 out of 27 worldwide) have been reported. The genome sequence analyses of these viruses revealed that both the eastern and western topotypes as well as their reassortant strains are present in India. It further revealed that some of these viruses are very close to live vaccines used in other countries. The severe economic concern justifies the need to develop sensitive and reliable diagnostic tests for BT. The virus isolation followed by identification by electron microscopy is gold standard test, but it is time consuming and not easily available in all the laboratories. Therefore, nucleic acid-based rapid diagnostic tests such as PCR, real-time PCR etc. are used nowadays. The BT control program in India includes vector control as well as effective vaccination. The vector population is controlled by vector traps, synthetic pesticides and some of the herbal compounds. For effective vaccination, the serotypes prevalent in a particular geographical area must be known, which can be achieved by continuous monitoring and sero-surveillance of disease. The multivalent inactivated vaccines are more suitable for India in comparison to modified live vaccines as the latter may turn to virulent and may lead to severe outbreak of the disease. PMID- 26666182 TI - Transolfactory neuroinvasion by viruses threatens the human brain. AB - Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and influenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. This article briefly summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses--HSV-1 and influenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis. PMID- 26666183 TI - Immune response of mice to non-adapted avian influenza A virus. AB - Human infections with avian influenza A viruses (IAVs) without or with clinical symptoms of disease were recently reported from several continents, mainly in high risk groups of people, who came into the contact with infected domestic birds or poultry. It was shown that avian IAVs are able to infect humans directly without previous adaptation, however, their ability to replicate and to cause a disease in this new host can differ. No spread of these avian IAVs among humans has been documented until now, except for one case described in Netherlands in the February of 2003 in people directly involved in handling IAV (H7N7)-infected poultry. The aim of our work was to examine whether a low pathogenic avian IAV can induce a virus-specific immune response of biological relevancy, in spite of its restricted replication in mammals. As a model we used a low pathogenic virus A/Duck/Czechoslovakia/1956 (H4N6) (A/Duck), which replicated well in MDCK cells and produced plaques on cell monolayers, but was unable to replicate productively in mouse lungs. We examined how the immune system of mice responds to the intranasal application of this non-adapted avian virus. Though we did not prove the infectious virus in lungs of mice following A/Duck application even after its multiple passaging in mice, we detected virus-specific vRNA till day 8 post infection. Moreover, we detected virus-specific mRNA and de novo synthesized viral nucleoprotein (NP) and membrane protein (M1) in lungs of mice on day 2 and 4 after exposure to A/Duck. Virus-specific antibodies in sera of these mice were detectable by ELISA already after a single intranasal dose of A/Duck virus. Not only antibodies specific to the surface glycoprotein hemagglutinin (HA) were induced, but also antibodies specific to the NP and M1 of IAV were detected by Western blot and their titers increased after the second exposure of mice to this virus. Importantly, antibodies neutralizing virus A/Duck were proved in mouse immune sera after the second dose of virus and a slight increase of mRNA expression of immune mediators tumor necrosis factor alpha (TNF-alpha) and IP10 has been observed in lungs of these mice 48 hr after the infection. These observations correspond to the limited replication ability of the virus in mice and provided an important information about its ability to induce virus-specific antibodies, including those neutralizing virus, even without the previous virus adaptation to the new mammalian host. Such antibodies could consequently influence the immune potential of exposed individuals and their defensive capability against the newly emerged, even more virulent IAV. PMID- 26666184 TI - Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties. AB - M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pancik et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1alpha). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines. PMID- 26666185 TI - Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense. AB - We have studied the impact of simultaneous infection of mice with murine gammaherpesvirus (MHV) and influenza A virus (IAV) on the immune response and pathogenesis of both infections. After a persistent MHV-68 herpesviral infection had been established, the same mice were super-infected with IAV. Individual parameters of MHV infection (viral DNA detection in organs and blood) and numbers of leukocytes in lungs and spleens were determined. With regard to the assumed reactivation of MHV-68 (mainly in lungs, spleen, thymus and peritoneal exudate cells) we focused our attention on the detection of transcripts, typical either for lytic infection (ORF50) and/or for latency (ORF73). Herpesviral DNA was detected in above mentioned organs in several intervals during the acute phase of IAV co-infection, but the expression of monitored transcripts was lower, i.e. it has decreased. Though the reason for such limited expression during acute influenza superinfection remains unclear, it is unambiguous that lower MHV-68 expression was detected in lungs and peritoneal exudate cells (PECs) from 3rd to 10th day after co-infection with IAV. Furthermore, our study showed that the ongoing gammaherpesvirus latency in co-infected mice affected the number of cytotoxic T-lymphocytes and neutrophils during the acute IAV infection and lowered their deviations from that of non-infected mice. Therefore, we suppose that co-infection with herpes and influenza viruses could be mutually beneficial for the host by promoting its defense against both viruses. PMID- 26666186 TI - Simultaneous detection of papaya ringspot virus, papaya leaf distortion mosaic virus, and papaya mosaic virus by multiplex real-time reverse transcription PCR. AB - Both the single infection of papaya ringspot virus (PRSV), papaya leaf distortion mosaic virus (PLDMV) or papaya mosaic virus (PapMV) and double infection of PRSV and PLDMV or PapMV which cause indistinguishable symptoms, threaten the papaya industry in Hainan Island, China. In this study, a multiplex real-time reverse transcription PCR (RT-PCR) was developed to detect simultaneously the three viruses based on their distinctive melting temperatures (Tms): 81.0+/-0.8 degrees C for PRSV, 84.7+/-0.6 degrees C for PLDMV, and 88.7+/-0.4 degrees C for PapMV. The multiplex real-time RT-PCR method was specific and sensitive in detecting the three viruses, with a detection limit of 1.0*10(1), 1.0*10(2), and 1.0*10(2) copies for PRSV, PLDMV, and PapMV, respectively. Indeed, the reaction was 100 times more sensitive than the multiplex RT-PCR for PRSV, and 10 times more sensitive than multiplex RT-PCR for PLDMV. Field application of the multiplex real-time RT-PCR demonstrated that some non-symptomatic samples were positive for PLDMV by multiplex real-time RT-PCR but negative by multiplex RT-PCR, whereas some samples were positive for both PRSV and PLDMV by multiplex real-time RT-PCR assay but only positive for PLDMV by multiplex RT-PCR. Therefore, this multiplex real-time RT-PCR assay provides a more rapid, sensitive and reliable method for simultaneous detection of PRSV, PLDMV, PapMV and their mixed infections in papaya. PMID- 26666187 TI - Differentially expressed genes in healthy and plum pox virus-infected Nicotiana benthamiana plants. AB - Viruses use both material and energy sources of their hosts and redirect the production of disposable compounds in order to make viral replication more efficient. Metabolism of infected organisms is modified by these enhanced requirements as well by their own defense response. Resulting complex story consists of many regulation events on various gene expression levels. Elucidating these processes may contribute to the knowledge on virus-host interactions and to evolving new antiviral strategies. In our work we applied a subtractive cloning technique to compare the transcriptomes of healthy and plum pox virus (PPV) infected Nicotiana benthamiana plants. Several genes were found to be induced or repressed by the PPV infection. The induced genes were mainly related to general stress response or photosynthesis, several repressed genes could be connected with growth defects evoked by the infection. Interestingly, some genes usually up regulated by fungal or bacterial infection were found repressed in PPV-infected plants. Potential involvement of particular differently expressed genes in the process of PPV infection is discussed. PMID- 26666188 TI - Sequence analysis and genetic diversity of five new Indian isolates of cucumber mosaic virus. AB - Cucumber mosaic virus (CMV) is an important virus since it causes severe losses to many economically important crops worldwide. Five new isolates of CMV were isolated from naturally infected Hippeastrum hybridum, Dahlia pinnata, Hemerocallis fulva, Acorus calamus and Typhonium trilobatum plants, all exhibiting severe leaf mosaic symptoms. For molecular identification and sequence analyses, the complete coat protein (CP) gene of these isolates was amplified by RT-PCR. The resulting amplicons were cloned and sequenced and isolates were designated as HH (KP698590), DP (JF682239), HF (KP698589), AC (KP698588) and TT (JX570732). For study of genetic diversity among these isolates, the sequence data were analysed by BLASTn, multiple alignment and generating phylogenetic trees along with the respective sequences of other CMV isolates available in GenBank Database were done. The isolates under study showed 82-99% sequence diversity among them at nucleotide and amino acid levels; however they showed close relationships with CMV isolates of subgroup IB. In alignment analysis of amino acid sequences of HH and AC isolates, we have found fifteen and twelve unique substitutions, compared to HF, DP and TT isolates, suggesting the cause of high genetic diversity. PMID- 26666189 TI - Epigenetic modification of Rta (ORF50) promoter is not responsible for distinct reactivation patterns of murine gammaherpesviruses. AB - Gammaherpesviruses-encoded replication and transcription activator (Rta) (ORF50) plays an essential role in the initiation of viral lytic gene expression and reactivation from latency. The Rta expression is influenced by many viral and cellular factors, including epigenetic modifications, mainly DNA methylation and histone modifications. Murine gammaherpesvirus 68 (MHV-68), belonging to the species Murid herpesvirus (MuHV-4), is widely used as a model to study human gammaherpesvirus infections in vitro as well as in vivo. Recent studies of the MHV-68 Rta promoter revealed the effect of DNA demethylation and histone acetylation, induced by the inhibitor of histone deacetylase trichostatin A (TSA), on the MHV-68 reactivation from latency. Two other strains of MuHV-4, MHV 72 and MHV-4556, possess several unique properties, which distinguish them from strain MHV-68. Recently discovered reduced capacity of MHV-72 and MHV-4556 to reactivate from latency may be related to different methylation/demethylation patterns of the promoter regulatory region of the Rta. Here, we investigated the epigenetic regulation of the Rta promoter of three murine gammaherpesvirus strains, MHV-68, MHV-72 and MHV-4556, during latency and reactivation in vivo. However, we did not find any differences between Rta of MHV-68, MHV-72 and MHV 4556 and its epigenetic regulation during lytic infection, latency and de novo infection after ex vivo and in vivo reactivation induced by TSA. We confirmed that the treatment with TSA successfully induced demethylation of the Rta promoter regions of all three studied strains. Moreover, we have shown that the primary sequence of Rta and its promoter is identical for all three strains. PMID- 26666190 TI - Protective efficacy of IFN-omega AND IFN-lambdas against influenza viruses in induced A549 cells. AB - The interferon system represents one of the components of the first line defence against influenza virus infection. Interferon omega (IFN-omega) is antigenetically different from IFN-alpha and IFN-beta and can affect patients who are resistant to these IFNs. To improve the biological characterization of IFN omega, we compared its activity with those of type I and type III IFNs in induced A549 cells. The antiviral effect on IFN-stimulated A549 cells was most apparent after infection with avian influenza virus. IFN-omega had statistically significant antiviral activity although less than IFN-beta1a, IFN-lambda1, or IFN lambda2. On the other hand, IFN-omega appeared more efficient than IFN-alpha2. Our results also indicate that IFN-lambdas were more suitable against human highly pathogenic virus. In this case, IFN-lambda1 and IFN-lambda2 were more potent than type I IFNs. PMID- 26666191 TI - Cells transformed by murine herpesvirus 68 (MHV-68) release compounds with transforming and transformed phenotype suppressing activity resembling growth factors. AB - In this study, we investigated the medium of three cell lines transformed with murine herpesvirus 68 (MHV-68) in vitro and in vivo, 68/HDF, 68/NIH3T3, and S11E, for the presence of compounds resembling growth factors of some herpesviruses which have displayed transforming and transformed phenotype suppressing activity in normal and tumor cells. When any of spent medium was added to cell culture we observed the onset of transformed phenotype in baby hamster kidney cells (BHK-21) cells and transformed phenotype suppressing activity in tumor human epithelial cells (HeLa). In media tested, we have identified the presence of putative growth factor related to MHV-68 (MHGF-68). Its bivalent properties have been blocked entirely by antisera against MHV-68 and two monoclonal antibodies against glycoprotein B (gB) of MHV-68 suggesting viral origin of MHGF-68. The results of initial efforts to separate MHGF-68 on FPLC Sephadex G15 column in the absence of salts revealed the loss of its transforming activity but transformed phenotype suppressing activity retained. On the other hand, the use of methanol-water mobile phase on RP-HPLC C18 column allowed separation of MHGF-68 to two compounds. Both separated fractions, had only the transforming activity to normal cells. Further experiments exploring the nature and the structure of hitherto unknown MHGF-68 are now in the progress to characterize its molecular and biological properties. PMID- 26666192 TI - Characterization of the nuclear localization signals of duck circovirus replication proteins. AB - Duck circovirus (DuCV) possess a circular, single-stranded DNA genome that requires the replication protein (Rep) for its replication. Based on the viral genotype, there are two categories of Rep proteins: Rep1 and Rep2. To characterize the nuclear localization signals (NLSs) conferring the nuclear localization of the Rep proteins, defined coding regions of the rep gene of two genotypes of DuCV were cloned and co-expressed with the red fluorescent protein DsRed2. The results showed that deleting the putative N-terminal NLS located at amino acid residues 10-37 of Rep1 and Rep2 abrogated nuclear translocation, while deleting the putative C-terminal NLS located at residues 244-274 of Rep1 did not significantly alter its subcellular localization, confirming that only the NLS located at residues 10-37 in the N-termini of the Rep proteins had nuclear targeting activity. PMID- 26666193 TI - PPV susceptibility of commonly used peach rootstock-scion combinations. AB - Sharka disease is one of the most devastating plant epidemics of Prunus species, caused by plum pox virus (PPV). The viral infection affects the fruits by weight loss and degradation of quality properties. Breeding of resistant rootstocks and cultivars is one of the most effective disease control methods. PPV determines the peach production all over the world. On the world's fruit production list peach is in the sixth, in the Mediterranean region in the fourth place. In this study new data were shown about PPV susceptibility of commonly used rootstock scion combinations from Hungary. Reverse transcription PCR (RT-PCR) analysis was conducted on the samples from a commercial orchard; the results were evaluated by chi-square test and binary logistic regression. Four rootstock ('GF677', 'PeMa', 'Cadaman' and almond seedlings) and three scion cultivars (Prunus persicae 'Michelini', 'Babygold 6' and 'Cresthaven') were included in this experiment. The rootstocks did not show any significant differences in regard to the resistance of the virus infection (40-50%), but in case of scions, strong significant relations were observed. In case of the combinations there were results in both directions; tolerant and susceptible combinations were observed as well. PMID- 26666194 TI - The prevalence of human papillomavirus in patients with oral lichen planus and normal oral mucosa. PMID- 26666195 TI - On the mineral core of ferritin-like proteins: structural and magnetic characterization. AB - It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction. PMID- 26666197 TI - Synergistic multi-doping effects on the Li7La3Zr2O12 solid electrolyte for fast lithium ion conduction. AB - Here, we investigate the doping effects on the lithium ion transport behavior in garnet Li7La3Zr2O12 (LLZO) from the combined experimental and theoretical approach. The concentration of Li ion vacancy generated by the inclusion of aliovalent dopants such as Al(3+) plays a key role in stabilizing the cubic LLZO. However, it is found that the site preference of Al in 24d position hinders the three dimensionally connected Li ion movement when heavily doped according to the structural refinement and the DFT calculations. In this report, we demonstrate that the multi-doping using additional Ta dopants into the Al-doped LLZO shifts the most energetically favorable sites of Al in the crystal structure from 24d to 96 h Li site, thereby providing more open space for Li ion transport. As a result of these synergistic effects, the multi-doped LLZO shows about three times higher ionic conductivity of 6.14 * 10(-4) S cm(-1) than that of the singly-doped LLZO with a much less efforts in stabilizing cubic phases in the synthetic condition. PMID- 26666198 TI - One-step detection of pathogens and cancer biomarkers by the naked eye based on aggregation of immunomagnetic beads. AB - This report shows that immunomagnetic beads (IMBs) can act as the optical readout for assays, in addition to serving as the carrier for purification/separation. Under the influence of an external magnet, IMBs are attracted to coat one side of a test tube. IMBs specifically bound to targets can form a narrow brown stripe, whereas free IMBs will form a diffuse, yellow coating on the side of the test tube. Target analytes can aggregate initially dispersed IMBs in a sample concentration-dependent manner, yielding a color change from yellow to brown that can be seen with the naked eye. This assay combines the convenience of a lateral flow assay, allowing a one-step assay to finish within 15 min, with the sensitivity of an enzyme-linked immonosorbent assay. PMID- 26666199 TI - Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations: A Review. AB - Obesity is considered to be an epidemic disease, and it is associated with several metabolic disorders. Pharmacological treatments currently available are not effective for prolonged treatment duration. So, people are looking toward new therapeutic approach such as herbal ingredients. Since ancient periods, different herbs have been used for remedy purposes such as anti-obesity, antidiabetes, and antiinflammatory. Among the several herbal ingredients, Aloe vera (Aloe barbadensis Miller) is widely used to curb the metabolic complications. Till date, reports are not available for the side effects of A. vera. Several researchers are used to different solvents such as aqueous solution, alcohol, ethanol, and chloroform for the A. vera extract preparations and studied their hypoglycemic and hypolipidemic effects in animal and human studies. Furthermore, little information was recorded with the active compounds extracted from the A. vera and their anti-obesity and antidiabetic effects in clinical studies. In this review, we made an attempt to compile all the available literature by using different search engines (PubMed, Scopus, and Google Scholar) on the A. vera extract preparations and the possible mechanism of action involved in carbohydrate and lipid metabolism. PMID- 26666200 TI - Metabolic engineering of acid resistance elements to improve acid resistance and propionic acid production of Propionibacterium jensenii. AB - Propionic acid (PA) and its salts are widely used in the food, pharmaceutical, and chemical industries. Microbial production of PA by propionibacteria is a typical product-inhibited process, and acid resistance is crucial in the improvement of PA titers and productivity. We previously identified two key acid resistance elements-the arginine deaminase and glutamate decarboxylase systems that protect propionibacteria against PA stress by maintaining intracellular pH homeostasis. In this study, we attempted to improve the acid resistance and PA production of Propionibacterium jensenii ATCC 4868 by engineering these elements. Specifically, five genes (arcA, arcC, gadB, gdh, and ybaS) encoding components of the arginine deaminase and glutamate decarboxylase systems were overexpressed in P. jensenii. The activities of the five enzymes in the engineered strains were 26.7-489.0% higher than those in wild-type P. jensenii. The growth rates of the engineered strains decreased, whereas specific PA production increased significantly compared with those of the wild-type strain. Among the overexpressed genes, gadB (encoding glutamate decarboxylase) increased PA resistance and yield most effectively; the PA resistance of P. jensenii-gadB was more than 10-fold higher than that of the wild-type strain, and the production titer, yield, and conversion ratio of PA reached 10.81 g/L, 5.92 g/g cells, and 0.56 g/g glycerol, representing increases of 22.0%, 23.8%, and 21.7%, respectively. We also investigated the effects of introducing these acid resistance elements on the transcript levels of related enzymes. The results showed that the expression of genes in the engineered pathways affected the expression of the other genes. Additionally, the intracellular pools of amino acids were altered as different genes were overexpressed, which may further contribute to the enhanced PA production. This study provides an effective strategy for improving PA production in propionibacteria; this strategy may be useful for the production of other organic acids. Biotechnol. Bioeng. 2016;113: 1294-1304. (c) 2015 Wiley Periodicals, Inc. PMID- 26666201 TI - A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder. AB - Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant-associated with reduced SNX7 expression-to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1beta and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID- 26666202 TI - Cocaine attenuates blood flow but not neuronal responses to stimulation while preserving neurovascular coupling for resting brain activity. AB - Cocaine affects neuronal activity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced changes in cerebral blood flow (CBF) reflect neuronal activation or its vasoactive effects. Here we assessed the effects of acute cocaine on both resting-state and stimulation responses to investigate cocaine's effects on neurovascular coupling and to differentiate its effects on neuronal activity from its vasoactive actions. We concurrently measured cortical field potentials via thinned-skull electroencephalography recordings and CBF with laser Doppler flowmetry in the rat's somatosensory cortex for both resting state and forepaw stimulation before and following cocaine administration (1 mg kg(-1), intravenously). Results show both resting-state field potentials and CBF were depressed after cocaine administration (19.8+/-4.7% and 52.1+/-13.4%, respectively) and these changes were strongly correlated with each other (r=0.81, P<0.001), indicating that cocaine did not affect neurovascular coupling at rest and that the reduction in resting CBF reflected reduction in synchronized spontaneous neuronal activity rather than vasoconstriction. In contrast, the forepaw stimulation-evoked neuronal activity was not changed by cocaine (P=0.244), whereas the CBF to the stimulation was reduced 49.9+/-2.6% (P=0.028) gradually recovering ~20 min after cocaine injection, indicating that neurovascular coupling during stimulation was temporarily disrupted by cocaine. Neurovascular uncoupling by cocaine during stimulation but not during rest indicates that distinct processes might underlie neurovascular regulation for both stimulation and spontaneous activity. The greater reductions by cocaine to the stimulation-induced CBF increases than to the background CBF should be considered when interpreting functional MRI studies comparing activation responses between controls and cocaine abusers. Neurovascular uncoupling could contribute to cocaine's neurotoxicity, particularly for stimulation conditions when CBF might be insufficient to cover for the energetic demands of neuronal tissue. PMID- 26666203 TI - The volumes of subcortical regions in depressed and healthy individuals are strikingly similar: a reinterpretation of the results by Schmaal et al. PMID- 26666204 TI - Polygenic associations of neurodevelopmental genes in suicide attempt. AB - The risk for suicidal behavior (SB) is elevated in schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), but also occurs in subjects without psychiatric diagnoses. Genome-wide association studies (GWAS) on SB may help to understand this risk, but have been hampered by low power due to limited sample sizes, weakly ascertained SB or a reliance on single-nucleotide protein (SNP)-by-SNP analyses. Here, we tried to mitigate such issues with polygenic risk score (PRS) association tests combined with hypothesis-driven strategies using a family-based sample of 660 trios with a well-ascertained suicide attempt (SA) outcome in the offspring (Genetic Investigation of Suicide and SA, GISS). Two complementary sources of PRS information were used. First, a PRS that was discovered and validated in the GISS SA revealed the polygenic association of SNPs in 750 neurodevelopmental genes, which was driven by the SA phenotype, rather than the major psychiatric diagnoses. Second, a PRS based on three different genome-wide association studies (on SCZ, BPD or MDD) from the Psychiatric Genomics Consortium (PGC) showed an association of the PGC-SCZ PRS in the SA subjects with and without major psychiatric diagnoses. We characterized the PGC-SCZ overlap in the SA subjects without diagnoses. The extended major histocompatibility complex region did not contribute to the overlap, but we delineated the genic overlap to neurodevelopmental genes that partially overlapped with those identified by the GISS PRS. Among the 590 SA polygenes implicated here, there were several developmentally important functions (cell adhesion/migration, small GTPase and receptor tyrosine kinase signaling), and 16 of the SA polygenes have previously been studied in SB (BDNF, CDH10, CDH12, CDH13, CDH9, CREB1, DLK1, DLK2, EFEMP1, FOXN3, IL2, LSAMP, NCAM1, nerve growth factor (NGF), NTRK2 and TBC1D1). These novel genome-wide insights, supported by two lines of evidence, suggested the importance of a polygenic neurodevelopmental etiology in SB, even in the absence of major psychiatric diagnoses. PMID- 26666205 TI - Structure and function of neonatal social communication in a genetic mouse model of autism. AB - A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup-mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor. PMID- 26666207 TI - Engineering Polymer Hydrogel Nanoparticles for Lymph Node-Targeted Delivery. AB - The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds. PMID- 26666206 TI - Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings. AB - Patients diagnosed with psychotic disorders (for example, schizophrenia and bipolar disorder) have elevated risks of committing violent acts, particularly if they are comorbid with substance misuse. Despite recent insights from quantitative and molecular genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotypes, there is currently a lack of large-scale studies that have specifically examined the aetiological links between psychotic disorders and violence. Using a sample of all Swedish individuals born between 1958 and 1989 (n=3 332 101), we identified a total of 923 259 twin-sibling pairs. Patients were identified using the National Patient Register using validated algorithms based on International Classification of Diseases (ICD) 8-10. Univariate quantitative genetic models revealed that all phenotypes (schizophrenia, bipolar disorder, substance misuse, and violent crime) were highly heritable (h(2)=53-71%). Multivariate models further revealed that schizophrenia was a stronger predictor of violence (r=0.32; 95% confidence interval: 0.30-0.33) than bipolar disorder (r=0.23; 0.21-0.25), and large proportions (51-67%) of these phenotypic correlations were explained by genetic factors shared between each disorder, substance misuse, and violence. Importantly, we found that genetic influences that were unrelated to substance misuse explained approximately a fifth (21%; 20-22%) of the correlation with violent criminality in bipolar disorder but none of the same correlation in schizophrenia (Pbipolar disorder<0.001; Pschizophrenia=0.55). These findings highlight the problems of not disentangling common and unique sources of covariance across genetically similar phenotypes as the latter sources may include aetiologically important clues. Clinically, these findings underline the importance of assessing risk of different phenotypes together and integrating interventions for psychiatric disorders, substance misuse, and violence. PMID- 26666208 TI - The c.64_80del SMIM1 allele is segregating in the Hutterite population. AB - BACKGROUND: The high-incidence red blood cell (RBC) antigen Vel is coded by SMIM1 (small-membrane molecule 1 gene), where a homozygous 17 base pair deletion underlies the majority of Vel- phenotypes. Because anti-Vel has been reported to cause severe hemolytic transfusion reactions and periodically hemolytic disease of the newborn and fetus, identification of individuals negative for Vel is clinically important. STUDY DESIGN AND METHODS: RBCs from the members of a large three-generation Hutterite family were serologically determined to be Vel+(w) . Genomic DNA from these family members was polymerase chain reaction amplified and analyzed for SMIM1 polymorphisms by either Sanger sequencing or restriction fragment length polymorphisms. SMIM1 genotyping was also conducted on DNA from an additional 104 Hutterites. RESULTS: All family members whose RBCs weakly expressed the Vel antigen were found to be heterozygous for the c.64_80del mutation in SMIM1. Of the 104 additional Hutterite samples, four were found to be heterozygous for the same SMIM1 mutation. CONCLUSION: After emigrating to the United States and Canada, the Hutterite population has expanded dramatically. Alleles that initially entered the population have been maintained within the population. The c.64_80del null allele of SMIM1 is one such allele, thus having implications for transfusion medicine and child or maternal health. PMID- 26666210 TI - A Step into an eco-Compatible Future: Iron- and Cobalt-catalyzed Borrowing Hydrogen Transformation. AB - Living on borrowed hydrogen: Recent developments in iron- and cobalt-catalyzed borrowing hydrogen have shown that economically reliable catalysts can be used in this type of waste-free reactions. By using well-defined inexpensive catalysts, known reactions can now be run efficiently without the necessary use of noble metals; however, in addition new types of reactivity can also be discovered. PMID- 26666211 TI - Amplified binding-induced homogeneous assay through catalytic cycling of analyte for ultrasensitive protein detection. AB - By using the principle of binding-induced DNA assembly, we have developed a novel homogeneous assay that is able to convert an affinity protein binding event into a predesigned DNA assembly. The assembled DNA sequence can be ligated into an intact DNA strand and hundreds of DNA hairpins can be cleaved by a nicking endonuclease. Each cleavage releases a single-stranded DNA (ssDNA) probe that is initially caged in the DNA hairpin. This released ssDNA probe can then turn on the fluorescence signal by desorbing a fluorescently-labelled complementary DNA probe from graphene oxide through hybridization. We demonstrate that this homogeneous, isothermal, and amplifiable assay can be tailored to detect a number of proteins, including a cancer biomarker, human prostate specific antigen, at picomolar levels in both buffer and human serum samples. PMID- 26666212 TI - Theoretical study of excited states of DNA base dimers and tetramers using optimally tuned range-separated density functional theory. AB - Excited states of various DNA base dimers and tetramers including Watson-Crick H bonding and stacking interactions have been investigated by time-dependent density functional theory using nonempirically tuned range-separated exchange (RSE) functionals. Significant improvements are found in the prediction of excitation energies and oscillator strengths, with results comparable to those of high-level coupled-cluster (CC) models (RI-CC2 and EOM-CCSD(T)). The optimally tuned RSE functional significantly outperforms its non-tuned (default) version and widely-used B3LYP functional. Compared to those high-level CC benchmarks, the large mean absolute deviations of conventional functionals can be attributed to their inappropriate amount of exact exchange and large delocalization errors which can be greatly eliminated by tuning approach. Furthermore, the impacts of H bonding and pi-stacking interactions in various DNA dimers and tetramers are analyzed through peak shift of simulated absorption spectra as well as corresponding change of absorption intensity. The result indicates the stacking interaction in DNA tetramers mainly contributes to the hypochromicity effect. The present work provides an efficient theoretical tool for accurate prediction of optical properties and excited states of nucleobase and other biological systems. (c) 2015 Wiley Periodicals, Inc. PMID- 26666209 TI - Unique features of long non-coding RNA biogenesis and function. AB - Long non-coding RNAs (lncRNAs) are a diverse class of RNAs that engage in numerous biological processes across every branch of life. Although initially discovered as mRNA-like transcripts that do not encode proteins, recent studies have revealed features of lncRNAs that further distinguish them from mRNAs. In this Review, we describe special events in the lifetimes of lncRNAs - before, during and after transcription - and discuss how these events ultimately shape the unique characteristics and functional roles of lncRNAs. PMID- 26666213 TI - Experience in optimizing fertility outcomes in men with congenital adrenal hyperplasia due to 21 hydroxylase deficiency. AB - OBJECTIVE: Men with congenital adrenal hyperplasia (CAH) have impaired fertility. We aimed to assess fertility outcomes and the importance of hypogonadotropic hypogonadism, testicular failure and the presence of testicular adrenal rest tumours (TART). DESIGN: Retrospective analysis of men attending an adult CAH clinic in a tertiary centre. PATIENTS: Fifty men with CAH due to 21 hydroxylase deficiency were identified of whom 35 were salt wasting and 15 were non-salt wasting. MEASUREMENTS: Review of fertility history and parameters including luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, 17 hydroxyprogesterone (17-OHP), semen analysis and the presence of testicular adrenal rest tissue (TART) on ultrasound. RESULTS: TART were detected by ultrasound in 21 (47%), and their presence was associated with an elevated FSH (P = 0.01). Severe oligospermia was present in 11 of 23 (48%), and this was associated with an elevated FSH (P = 0.02), suppressed LH (P < 0.01) and TART (P = 0.03) when compared to those with a sperm count >5 * 10(6) per ml. Of those that desired fertility, 10 of 17 (59%) required treatment intensification and four underwent in vitro fertilization. Intensification resulted in a rise in median LH (0.6-4.3 IU/l; P = 0.01). Live birth rate was 15 of 17 (88%) with a median (range) time to conception of 8 (0-38) months. CONCLUSIONS: Suppressed LH is a marker for subfertility and is often reversible. Testicular failure is closely associated with TART formation. If TART are detected, sperm cryopreservation should be offered given the risk of progression to irreversible testicular failure. Male fertility in CAH can be improved by intensified treatment and assisted reproductive technology. PMID- 26666214 TI - The Value of Serum Prolidase Activity in Progression of Microalbuminuria in Patients With Type 2 Diabetes Mellitus. AB - BACKGROUND: Prolidase is a cytosolic exopeptidase that plays a pivotal role in collagen turnover. Diabetic nephropathy (DN) is associated with structural changes in glomerular basement membrane accompanied with increased amounts of collagen. Prolidase is known to be abundant in kidney and collagen accumulation is increased in DN, so we aimed to determine the value of serum prolidase activity (SPA) in predicting the progression of nephropathy in type 2 diabetes mellitus (DM). METHODS: Thirty type 2 DM patients having microalbuminuria (microalbuminuric group), 30 type 2 DM patients without albuminuria (normoalbuminuric group), and 28 healthy controls (control group) were enrolled. Study groups had similar age, sex distribution, and body mass index (BMI). RESULTS: Metabolic parameters, SPA and urinary microalbumin were determined. SPA was significantly higher in microalbuminuric group when compared with normoalbuminuric and control groups (P = 0.05 and P < 0.001, respectively). Triglyceride levels were significantly higher and high density lipoprotein cholesterol (HDL-C) levels were significantly lower in microalbuminuric group compared to control group (Both P < 0.05). SPA showed a negative correlation with HDL-C level and a positive correlation with urinary albumin excretion (r = 0.219, P < 0.05 and r = 0.39, P < 0.001 respectively). In regression analysis, albumin excretion was the sole parameter influencing SPA. CONCLUSION: SPA appears to be higher in type 2 DM patients having microalbuminuria compared to patients without microalbuminuria and healthy controls. The pathophysiological role and the significance of SPA in predicting DN need to be further evaluated. PMID- 26666215 TI - Detection of asymptomatic enthesitis in psoriasis patients: An onset of psoriatic arthritis? AB - Presence of asymptomatic joint involvement is recognized in patients with psoriasis. However, it remains elusive whether such patients develop psoriatic arthritis (PsA). The aim of the present study was to examine the incidence of asymptomatic joint lesions, in particular, enthesitis in patients with psoriasis vulgaris (PsV) and to further assess the clinical features. Eighteen PsV and 28 PsA patients were enrolled for examination by positron emission tomography/computed tomography (PET/CT) using (18) F-fluorodeoxyglucose (FDG). Any nail, scalp and intergluteal involvements were reported. Levels of serum C reactive protein (CRP), white blood cell (WBC) counts and erythrocyte sedimentation rate (ESR) were examined. All of the PsA patients showed FDG accumulation in the affected joints. Notably, asymptomatic enthesitis was detected in six out of 18 PsV patients (33%), and they were diagnosed as having subclinical PsA. Incidences of scalp, intergluteal and nail psoriasis in subclinical PsA patients were 100%, 83% and 64%, respectively, which were higher than those in PsV patients (67%, 25% and 40%, respectively). CRP, WBC counts and ESR were invariable between PsV and subclinical PsA groups. PET/CT imaging could discover asymptomatic enthesitis. Our data suggested that the subpopulation of subclinical PsA was much higher than expected. Higher prevalence of nail, scalp and intergluteal psoriasis confirmed the risk of PsA as previously described. PMID- 26666216 TI - Presence of a Physician Safety Champion Is Associated with a Reduction in Urinary Catheter Utilization in the Pediatric Intensive Care Unit. AB - BACKGROUND: Safety champions are effective in a variety of safety initiatives; however, there are no reports of their role in hospital-acquired infections prevention. OBJECTIVE: We aimed to describe the association of the presence of a physician safety champion with our urinary catheter device utilization ratios (DUR) in the Pediatric Intensive Care Unit (PICU). METHODS: Our PICU has incidence rates of catheter-associated urinary tract infections (CAUTI) and urinary catheter DUR above the 90th percentile. Using a quasi-experimental design, we compared our DUR when the PICU team was exposed and unexposed (champion's maternity leaves) to a physician safety champion. Hospital acquired infection (HAI) surveillance of all PICU admissions between April 1st 2009 and June 29th 2013 was done prospectively. To ensure stable acuity of the patient population over time, we used the central venous catheter (CVC) DUR as a control. RESULTS: The urinary catheter DUR was 0.44 (95% confidence interval [CI] 0.42 0.45) during the unexposed period versus 0.39 (95%CI 0.38-0.40) during the exposed period, for an absolute difference of 0.05 (95%CI 0.03-0.06; p<0.0001). The overall CVC DUR increased from 0.57 (95%CI 0.55-0.58) during the unexposed period to 0.63 (95%CI 0.61-0.64) during the exposed period, an absolute increase of 0.06 (95%CI 0.04-0.08; p<0.0001). Comparing the exposed and unexposed periods, adjusting for time trend, we observed a 17% decrease in the urinary catheter DUR when the safety champion was present (odds ratio [OR] 0.83; 95%CI 0.77-0.90). The rate of catheter-associated urinary tract infections did not change. CONCLUSIONS: The presence of a unit-based safety champion can have a positive impact on urinary catheter DUR in a PICU. PMID- 26666217 TI - Global spread of hypoxia in freshwater ecosystems during the last three centuries is caused by rising local human pressure. AB - The spread of hypoxia is a threat to aquatic ecosystem functions and services as well as to biodiversity. However, sparse long-term monitoring of lake ecosystems has prevented reconstruction of global hypoxia dynamics while inhibiting investigations into its causes and assessing the resilience capacity of these systems. This study compiles the onset and duration of hypoxia recorded in sediments of 365 lakes worldwide since AD 1700, showing that lacustrine hypoxia started spreading before AD 1900, 70 years prior to hypoxia in coastal zones. This study also shows that the increase of human activities and nutrient release is leading to hypoxia onset. No correlations were found with changes in precipitation or temperature. There is no evidence for a post-1980s return to well-oxygenated lacustrine conditions in industrialized countries despite the implementation of restoration programs. The apparent establishment of stable hypoxic conditions prior to AD 1900 highlights the challenges of a growing nutrient demand, accompanied by increasing global nutrient emissions of our industrialized societies, and climate change. PMID- 26666218 TI - Rebuttal by Lars Nybo and Carsten Lundby. PMID- 26666219 TI - Accessible heavier s-block dihydropyridines: structural elucidation and reactivity of isolable molecular hydride sources. AB - The straightforward metathesis of 1-lithio-2-tbutyl-1,2-dihydropyridine using metal tert-butoxide (Na/K) has resulted in the first preparation and isolation of a series of heavier alkali metal dihydropyridines. By employing donors, TMEDA, PMDETA and THF, five new metallodihydropyridine compounds were isolated and fully characterised. Three distinct structural motifs have been observed; a dimer, a dimer of dimers and a novel polymeric dihydropyridylpotassium compound, and the influence of cation pi-interactions therein has been discussed. Thermal volatility analysis has shown that these complexes have the potential to be used as simple isolable sodium or potassium hydride surrogates, which is confirmed in test reactions with benzophenone. PMID- 26666220 TI - Loss of Intra-Epithelial Endocervical Gamma Delta (GD) 1 T Cells in HIV-Infected Women. AB - PROBLEM: Human gamma delta (GD) T cells play a well-documented role in epithelial barrier surveillance and protection. Two subsets of GD T cells, defined by the use of either the Vdelta2 (GD2) or Vdelta1 (GD1) TCR, predominate. We hypothesized that endocervical GD T cells play important role in lower genital tract anti-HIV immune responses. METHOD OF STUDY: HIV-infected (n = 18) and HIV uninfected (n = 19) pre-menopausal women participating in the WIHS cohort were recruited. Frequency and phenotype of GD T cells were determined in endocervical cytobrush samples and peripheral blood by multicolor flow cytometry. RESULTS: We found depletion of GD2 cells in the blood of HIV-infected women as well as significant decrease in the frequency of endocervical GD1 cells compared to uninfected women. CONCLUSION: We report for the first time, the GD1 cells are a predominant endocervical T-cell subset that is significantly decreased in HIV infected women. PMID- 26666221 TI - The probability of readmission within 30 days of hospital discharge is positively associated with inpatient bed occupancy at discharge--a retrospective cohort study. AB - BACKGROUND: Previous work has suggested that given a hospital's need to admit more patients from the emergency department (ED), high inpatient bed occupancy may encourage premature hospital discharges that favor the hospital's need for beds over patients' medical interests. We argue that the effects of such action would be measurable as a greater proportion of unplanned hospital readmissions among patients discharged when the hospital was full than when not. In response, the present study tested this hypothesis by investigating the association between inpatient bed occupancy at the time of hospital discharge and the 30-day readmission rate. METHODS: The sample included all inpatient admissions from the ED at a 420-bed emergency hospital in southern Sweden during 2011-2012 that resulted in discharge before 1 December 2012. The share of unplanned readmissions within 30 days was computed for levels of inpatient bed occupancy of <95%, 95 100%, 100-105% and >105% at the hour of discharge. A binary logistic regression model was constructed to adjust for age, time of discharge, and other factors that could affect the outcome. RESULTS: In all, 32,811 visits were included in the study, 9.9% of which resulted in an unplanned readmission within 30 days of discharge. The proportion of readmissions was 9.0% for occupancy levels of <95% at the patient's discharge, 10.2% for 95-100% occupancy, 10.8% for 100-105% occupancy, and 10.5% for >105% occupancy (p = 0.0001). Results from the multivariate models show that the OR (95% CI) of readmission was 1.11 (1.01-1.22) for patients discharged at 95-100% occupancy, 1.17 (1.06-1.29) at 100-105% occupancy, and 1.15 (0.99-1.34) at >105% occupancy. CONCLUSIONS: Results indicate that patients discharged from inpatient wards at times of high inpatient bed occupancy experience an increased risk of unplanned readmission within 30 days of discharge. PMID- 26666222 TI - Mariner transposons are sailing in the genome of the blood-sucking bug Rhodnius prolixus. AB - BACKGROUND: The Triatomine bug Rhodnius prolixus is a vector of Trypanosoma cruzi, which causes the Chagas disease in Latin America. R. prolixus can also transfer transposable elements horizontally across a wide range of species. We have taken advantage of the availability of the 700 Mbp complete genome sequence of R. prolixus to study the dynamics of invasion and persistence of transposable elements in this species. RESULTS: Using both library-based and de novo methods of transposon detection, we found less than 6 % of transposable elements in the R. prolixus genome, a relatively low percentage compared to other insect genomes with a similar genome size. DNA transposons are surprisingly abundant and elements belonging to the mariner family are by far the most preponderant components of the mobile part of this genome with 11,015 mariner transposons that could be clustered in 89 groups (75 % of the mobilome). Our analysis allowed the detection of a new mariner clade in the R. prolixus genome, that we called nosferatis. We demonstrated that a large diversity of mariner elements invaded the genome and expanded successfully over time via three main processes. (i) several families experienced recent and massive expansion, for example an explosive burst of a single mariner family led to the generation of more than 8000 copies. These recent expansion events explain the unusual prevalence of mariner transposons in the R. prolixus genome. Other families expanded via older bursts of transposition demonstrating the long lasting permissibility of mariner transposons in the R. prolixus genome. (ii) Many non-autonomous families generated by internal deletions were also identified. Interestingly, two non autonomous families were generated by atypical recombinations (5' part replacement with 3' part). (iii) at least 10 cases of horizontal transfers were found, supporting the idea that host/vector relationships played a pivotal role in the transmission and subsequent persistence of transposable elements in this genome. CONCLUSION: These data provide a new insight into the evolution of transposons in the genomes of hematophagous insects and bring additional evidences that lateral exchanges of mobile genetics elements occur frequently in the R. prolixus genome. PMID- 26666223 TI - Improvement of hemispatial neglect by a see-through head-mounted display: a preliminary study. AB - BACKGROUND: Patients with right hemisphere damage are often unaware of, inattentive to and fail to interact with stimuli on their left side. This disorder, called hemispatial neglect, is a major source of disability. Inducing leftward ocular pursuit by optokinetic stimulation (OKS) relieves some of the signs of unilateral neglect. However, it is difficult to provide patients with a continuously moving background that is required for OKS. We studied whether OKS projected onto a see-through head-mounted display (HMD) would help treat neglect. METHODS: 14 patients with neglect after cerebral infarction performed line bisections on a computer screen, both with and without OKS that was either delivered by the HMD or on the same screen that was displaying the lines that were to be bisected. RESULTS: The line bisection performances were significantly different in the four conditions (P < 0.001). The post hoc analyses indicated that the rightward deviation observed in the control conditions on the line bisection tasks without OKS, improved significantly with the use OKS in both the HMD and screen conditions (alpha < 0.05). The results between the screen and HMD conditions were also different (alpha < 0.05). The OKS in the HMD condition corrected patients' rightward deviation more toward the actual midline than did the OKS provided during the screen condition. CONCLUSIONS: OKS projected onto the see-through HMD improved hemispatial neglect. The development of a portable device may aid in the treatment of neglect. PMID- 26666224 TI - Quantitative proteomics signature profiling based on network contextualization. AB - BACKGROUND: We present a network-based method, namely quantitative proteomic signature profiling (qPSP) that improves the biological content of proteomic data by converting protein expressions into hit-rates in protein complexes. RESULTS: We demonstrate, using two clinical proteomics datasets, that qPSP produces robust discrimination between phenotype classes (e.g. normal vs. disease) and uncovers phenotype-relevant protein complexes. Regardless of acquisition paradigm, comparisons of qPSP against conventional methods (e.g. t-test or hypergeometric test) demonstrate that it produces more stable and consistent predictions, even at small sample size. We show that qPSP is theoretically robust to noise, and that this robustness to noise is also observable in practice. Comparative analysis of hit-rates and protein expressions in significant complexes reveals that hit-rates are a useful means of summarizing differential behavior in a complex-specific manner. CONCLUSIONS: Given qPSP's ability to discriminate phenotype classes even at small sample sizes, high robustness to noise, and better summary statistics, it can be deployed towards analysis of highly heterogeneous clinical proteomics data. PMID- 26666225 TI - Sedentary time among spouses: a cross-sectional study exploring associations in sedentary time and behaviour in parents of 5 and 6 year old children. AB - BACKGROUND: Sedentary time is associated with obesity and is a risk factor for other adverse health outcomes. We examined how sedentary time and screen viewing (SV) behaviours in parents of young children are associated and whether associations differed for weekdays versus weekend days. METHODS: Data were from a cross sectional study (B-ProAct1v) based in Bristol, UK investigating associations between physical activity and SV in children and parents. Parents were eligible for analysis if they and their partner had both provided valid accelerometer data (290 dyads) or had both provided valid screen-viewing data (325 dyads). Multivariable regression models were used to examine associations of (a) sedentary behaviours and (b) self-reported time spent on weekdays and weekend days watching TV, using a PC, and using a phone in the dyads. Models were adjusted for the number of media items in the house, mothers' age and body mass index, and household index of multiple deprivation. RESULTS: Sedentary behaviour was lower at weekends than on weekdays for fathers and mothers. In contrast, the proportion of parents watching at least 2 h TV was higher on weekend days than on weekdays. Adjusted multivariable linear regression models suggested that 3 min of sedentary time on weekend days in fathers were associated with an additional minute of mothers' sedentary time (B 0.38; 95 % CI 0.26 to 0.49). Logistic regression indicated that mothers' screen use was positively predicted by fathers' use (e.g., the odds of a mother watching more than 2 h TV on a weekend day were increased fivefold if the father also watched this amount OR 5.09, 95 % CI 3.30 to 7.86), except for PC use at weekends where the association was reversed and the odds of mothers using a PC for more than 30 min per weekend day was halved if the father used a PC for this amount of time (OR 0.45, 95 % CI 0.22 to 0.94). CONCLUSIONS: Programmes that encourage at least one adult in the household to decrease sedentary behaviour and become more active, particularly at weekends, should be developed. PMID- 26666226 TI - Synthetic Calcite as a Scaffold for Osteoinductive Bone Substitutes. AB - Although a wide variety of biomaterials have been already proposed for use in bone tissue engineering, there is still need for man-made materials, which would combine support for osteogenesis with simplicity desirable for upscaling and costs reduction. In this study we have shown that synthetic calcite may serve as a scaffold for human osteoblasts transplantation. A simple dynamic system allows uniform and effective cell distribution. Cell viability and osteogenic phenotype were confirmed by XTT assay, alkaline phosphatase activity and selected osteoblast-specific genes expression. Extracellular matrix deposited by cells improved elasticity and made the whole system similar to the flexible composite material rather than to the brittle ceramic implants. It was revealed in the compression tests and also by the improved samples handling. Subcutaneous implantation of the cell-seeded calcite scaffolds to immunodeficient mice resulted in mineralized bone formation, which was confirmed histologically and by EPR analysis. The latter we propose as a method supplementary to histological analysis, for bone regeneration investigations. It specifically confirms the presence of bone mineral with a unique sensitivity and using bulk samples, which eliminates the risk of missing the material in the preparation. Our study resulted in development of a new osteogenic tissue engineered product based on man-made calcite. PMID- 26666227 TI - Multi-Joint Compensatory Effects of Unilateral Total Knee Arthroplasty During High-Demand Tasks. AB - Patients with total knee arthroplasty (TKA) demonstrate quadriceps weakness and functional limitations 1 year after surgery during daily tasks such as walking and stair climbing. Most biomechanical analyses of patients after TKA focus on quadriceps function and rarely investigate other lower-extremity muscles or high demand ambulatory activities of daily living. The purpose of this investigation was to quantify lower-extremity muscle forces in patients with unilateral TKA during high-demand tasks of pivoting and descending stairs. Five patients with unilateral TKA and five age and sex-matched controls performed three bilateral high-demand tasks: (1) step down from an 8-inch platform, (2) inside pivot: 90 degrees direction change toward planted limb, and (3) outside pivot: 90 degrees direction change away from planted limb. Subject-specific musculoskeletal simulations were created in OpenSim to determine joint angles, moments, and lower extremity muscle forces. The results indicate that patients with TKA adopt compensatory strategies at both the hip and knee. Patients with TKA demonstrated increased hip external rotation, decreased knee flexion, decreased quadriceps force, and decreased hip abductor force in all three tasks. These strategies are likely a result of quadriceps avoidance, which may stem from instability after TKA or a habitual strategy developed during the late stages of osteoarthritis. PMID- 26666228 TI - Soft Tissue Phantoms for Realistic Needle Insertion: A Comparative Study. AB - Phantoms are common substitutes for soft tissues in biomechanical research and are usually tuned to match tissue properties using standard testing protocols at small strains. However, the response due to complex tool-tissue interactions can differ depending on the phantom and no comprehensive comparative study has been published to date, which could aid researchers to select suitable materials. In this work, gelatin, a common phantom in literature, and a composite hydrogel developed at Imperial College, were matched for mechanical stiffness to porcine brain, and the interactions during needle insertions within them were analyzed. Specifically, we examined insertion forces for brain and the phantoms; we also measured displacements and strains within the phantoms via a laser-based image correlation technique in combination with fluorescent beads. It is shown that the insertion forces for gelatin and brain agree closely, but that the composite hydrogel better mimics the viscous nature of soft tissue. Both materials match different characteristics of brain, but neither of them is a perfect substitute. Thus, when selecting a phantom material, both the soft tissue properties and the complex tool-tissue interactions arising during tissue manipulation should be taken into consideration. These conclusions are presented in tabular form to aid future selection. PMID- 26666229 TI - Homicide in Chile: Trends 2000-2012. AB - BACKGROUND: Homicide, an external cause of morbidity and mortality, caused 473,000 deaths worldwide in 2012, a rate of 6.2 per 100,000 inhabitants. The aim of this study was to describe homicide mortality trends in Chile between 2000 and 2012 by year, gender, age group, geographic distribution (by zone and by region) and type of homicide. METHODS: This was a population-based study. Data for homicide mortality in Chile between 2000 and 2012 were used and they were provided by the Chilean Ministry of Health's Department of Statistics and Health Information (DEIS) and PAHO/WHO. The homicide mortality rates were calculated per 100,000 inhabitants. The study variables were year, geographic distribution, gender, age group and type of homicide. The annual percentage change (APC) of the rates was analyzed, and a logarithm of the rates by year and region was fitted by applying linear regression models. In addition, relative risks (RR) were calculated. 95% confidence intervals were considered in all the analyses. RESULTS: The average yearly rate of homicide (HMR) in Chile (2000-2012) was 4.9. The rates were higher in men (8.7) than in women (1.1), with a RR of 8.2. The rates were higher in the country's central zone (5.0), increasing in recent years in the southern zone, with a significant positive APC of 1.1%. The Aisen Region had the highest rate (7.6), although Antofagasta was the region with the most significant APC (3.1%). The highest rate (9.2) was verified in the 25 to 39 age group. The highest rate (5.5) was recorded in 2005. The most frequent type of homicide was assault with an object (44.8%). CONCLUSIONS: Although the homicide rates are higher in the southern zone of the country, the northern zone is showing a tendency to increase, becoming an even more serious problem, which not only affects those directly involved, but society as a whole. PMID- 26666231 TI - A modified scleral dissection technique with suprachoroidal drainage for canaloplasty. AB - PURPOSE: A modified canaloplasty technique is described that may facilitate the surgical procedure and potentially maximizes the intraocular pressure (IOP) lowering effect by altering both the trabecular and uveoscleral aqueous outflow. METHODS: The second deeper layer in the modified technique (about 3.5 * 4 mm, Fig. 1a, b) is not prepared in a lamellar fashion, but is cut down full-thickness to the choroid, hence opening the suprachoroidal space. Furthermore, this second deep scleral flap creates an additional aqueous outflow and drainage into the suprachoroidal space, thus possibly lowering the postoperative IOP by improving the natural uveoscleral outflow facility. RESULTS: Seventy-eight eyes operated with this modified technique in the last 12 months were retrospectively analysed. Mean IOP before surgery was 19.10 mmHg and patients applied 3.0 topical medications. Twelve months after surgery, the IOP was 13.5 mmHg and patients applied 1.0 topical medication; 52.6 % of patients did not use any topical therapy. DISCUSSION: The modified dissection canaloplasty technique potentially improves the IOP-lowering effect due to the creation of additional suprachoroidal drainage and simplifies the most complicated step of the surgery, as the scleral spur and the Schlemm's canal can be located using suprachoroidal access. PMID- 26666230 TI - Novel GLP-1 (Glucagon-Like Peptide-1) Analogues and Insulin in the Treatment for Alzheimer's Disease and Other Neurodegenerative Diseases. AB - The link between diabetes mellitus and Alzheimer's disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson's disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb. Several studies have shown the importance of both insulin and GLP-1 signalling on cognitive function, and many preclinical studies have been performed to evaluate the potential protective role of GLP-1 on the brain. Here we review the underlying mechanism of insulin and GLP-1 signalling in the CNS, as well as the preclinical data for the use of GLP-1 analogues such as liraglutide, exenatide and lixisenatide in neurodegenerative diseases. PMID- 26666232 TI - Evaluation of mechanical closure resistance of sutureless vitrectomy sclerotomies after conjunctival cauterization with bipolar diathermy forceps. AB - BACKGROUND: Suturing is the most widely used technique to close leaking sclerotomies after transconjunctival sutureless vitrectomy (TSV). However, with the aim of avoiding the disadvantages caused by conjunctival stitches, there have been described other closure techniques, such as the cauterization of the conjunctiva placed over the incisions. To continue advancing knowledge of the incisional occlusion effect achieved by conjunctival diathermy, it would be also interesting to study the wound closure resistance obtained under intraocular pressure (IOP) changes, given that in the early postoperative period eyes are subjected to pressure stress. In our study, we compare the mechanical resistance observed in sclerotomies treated with bipolar diathermy after TSV compared to that found in incisions in which cauterization was not performed. METHODS: This was an experimental, randomized, and observer-masked study in which 23-gauge TSV was performed in 80 cadaveric pig eyes. Once each vitrectomy was finished, cauterization was performed with bipolar diathermy forceps on the conjunctiva placed over one of the superior sclerotomy sites; no maneuver was performed over the other superior incision. IOP was gradually increased by means of the vitrectomy system (Accurus; Alcon Laboratories, TX) until one of the superior sclerotomies opened, allowing internal ocular solution to escape. RESULTS: In 35 % of cases (28 of 80 eyes), sclerotomies subjected to diathermy allowed intraocular fluid escape first (p = 0.01). When comparing opening pressure values, cauterized incisions leaked at significantly higher pressure levels than those in which diathermy was not applied (p < 0.001). CONCLUSIONS: Bipolar diathermy on sutureless sclerotomies has demonstrated to be, in our experimental model, an effective method for increasing the sclerotomy closure resistance. Although its use in vitrectomized eyes has previously been described, our study is the first to analyze the response of cauterized sclerotomies to IOP increases. PMID- 26666233 TI - Estimation of the Disc Damage Likelihood Scale in primary open-angle glaucoma: the Glaucoma Stereo Analysis Study. AB - PURPOSE: The Glaucoma Stereo Analysis Study (GSAS), a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We examined the associations between the Disc Damage Likelihood Scale (DDLS), a grading system for estimating glaucomatous ONH damage, and each parameter. METHODS: The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. ONH morphological parameters including the DDLS stage were calculated with prototype analysis software. Three independent graders classified each optic disc appearance into four different types: focal ischemic, myopic glaucomatous, senile sclerotic, and generalized enlargement. The correlations between the DDLS and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. RESULTS: The DDLS was correlated positively with baseline intraocular pressure and visual field pattern standard deviation, and negatively with visual field mean deviation. The DDLS was strongly correlated with vertical cup-to-disc ratio and horizontal cup-to-disc ratio positively, and with minimum rim-disc ratio negatively. The mean DDLS stage in the myopic glaucomatous type tended to be higher than the scores in other types. CONCLUSION: The DDLS obtained through three-dimensional ONH analysis correlates well with the severity of glaucomatous ONH and visual field damage. PMID- 26666234 TI - Prophylactic removal and microbiological evaluation of calcified plaques after pterygium surgery. AB - PURPOSE: The aim of this study was to investigate microbiological characteristics of prophylactically removed calcified plaques developed after pterygium excision, and to evaluate risk factors for the growth of microorganisms. METHODS: Only exposed calcified plaques developed at the same site of previous pterygium excision were prospectively removed in 15 eyes of 14 patients. Plaques were completely removed, divided into small pieces and evaluated for microbiological identification. Underlying scleral defects were reconstructed using a conjunctival autograft, amniotic membranes and scleral patch grafts according to the size and depth of the defects. Based on the results of microbiologic cultures, eyes were divided into two groups and risk factors for microbial growth were analyzed. RESULTS: At surgery, the mean age of the patients was 71.2 +/- 5.8 years and 71.4 % were females. The mean time interval between pterygium excision and calcified plaque removal was 19.3 +/- 13.8 years. Six of 15 (40 %) removed plaques showed bacterial growth, and Stenotrophomonas maltophilia was the most frequently isolated microorganism. The size of calcified plaques was the only risk factor for culture-positive results (p = 0.045). Underlying scleral defects were successfully repaired without any serious complication. CONCLUSIONS: Microorganisms can be isolated from calcified plaques developed at the site of previous pterygium excision, and the size of plaques is the only risk factor for culture-positive results. To remove potential source of infection, prophylactic removal of calcified plaques and scleral surface reconstruction should be considered, especially when the plaques are exposed and large. PMID- 26666235 TI - Reply to the letter of Zattoni et al. PMID- 26666237 TI - Comments on Kristensen et al.: Clinical value of FDG-PET/CT in suspected paraneoplastic syndromes: a retrospective analysis of 137 patients. PMID- 26666236 TI - Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial. AB - PURPOSE: Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. METHODS: Patients with acute MI and ejection fraction (EF) <= 45 % were randomized to cell therapy or to control and underwent thallium single photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. RESULTS: At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p < 0.001), without significant increase in LV mechanical dyssynchrony. During follow-up, there was a progressive increase in LV SD (p = 0.01). Baseline independent predictors of LV remodelling were perfusion SPECT defect size (p = 0.001), LVEF (p = 0.01) and a history of hypertension (p = 0.043). Bone marrow cell therapy did not affect the time-course of LV remodelling and dyssynchrony. CONCLUSIONS: LV remodelling 1 year after reperfused MI is associated with progressive LV dyssynchrony and is related to baseline infarct size and ejection fraction, without impact of cell therapy on this process. PMID- 26666238 TI - Symptomatic versus asymptomatic knees after bilateral total knee arthroplasty: what is the difference in SPECT/CT? AB - PURPOSE: The primary purpose of this retrospective study was to evaluate the differences of bone tracer uptake (BTU) in symptomatic and asymptomatic knees after bilateral total knee arthroplasty (TKA) and identify typical BTU patterns with regards to TKA component position and alignment. METHODS: A consecutive number of 37 patients after bilateral TKA were retrospectively included. The knees were grouped into symptomatic (group A) and asymptomatic (group B) knees. All patients underwent 99m-Tc-HDP-SPECT/CT. Coronal, rotational, and sagittal TKA component position was analysed in 3D reconstructed CT. BTU was anatomically localised and quantified using a validated standardized localization scheme. Maximum BTU values for each area were recorded and normalized values calculated. Signed log-rank test, chi-square test, paired t-tests, and Pearson correlations were used (p <0.05). RESULTS: Symptomatic TKAs were significantly more flexed and had a tendency to be more internally rotated when compared to asymptomatic ones (p < 0.05). In all regions, the mean BTU in asymptomatic knees was lower than in symptomatic knees. In both groups the highest mean BTU was found around the tibial stem (symptomatic 7.30; asymptomatic 6.30, p = 0.061) and at the tip of the tibial stem (symptomatic 5.49; asymptomatic 4.74, p = 0.062). Superior patellar regions showed higher BTU than inferior regions. The highest patellar BTU was found in the superior medial patella (symptomatic 4.99; asymptomatic 3.98, p = 0.048). The lowest BTU was found in the posterior femoral regions (flatsp, flatip, fmedsp, fmedip) (Table 3). Tibial and patellar areas showed twice as high mean BTUs than femoral areas (Fig. 3). A significant correlation of TKA component position and BTU was demonstrated. CONCLUSIONS: Distribution and intensity of BTU in SPECT/CT depends on TKA component position and alignment. In addition, typical BTU patterns in symptomatic and asymptomatic knees were identified. A profound knowledge of BTU pattern, TKA component position, and alignment helps to identify pathologies in patients after TKA. CLINICAL EVIDENCE: Diagnostic study, level II. PMID- 26666240 TI - Freewheelin' scientists: citing Bob Dylan in the biomedical literature. PMID- 26666239 TI - Early static (18)F-FET-PET scans have a higher accuracy for glioma grading than the standard 20-40 min scans. AB - PURPOSE: Current guidelines for glioma imaging by positron emission tomography (PET) using the amino acid analogue O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F FET) recommend image acquisition from 20-40 min post injection (p.i.). The maximal tumour-to-background evaluation (TBRmax) obtained in these summation images does not enable reliable differentiation between low and high grade glioma (LGG and HGG), which, however, can be achieved by dynamic (18)F-FET-PET. We investigated the accuracy of tumour grading using TBRmax values at different earlier time points after tracer injection. METHODS: Three hundred and fourteen patients with histologically proven primary diagnosis of glioma (131 LGG, 183 HGG) who had undergone 40-min dynamic (18)F-FET-PET scans were retrospectively evaluated. TBRmax was assessed in the standard 20-40 min summation images, as well as in summation images from 0-10 min, 5-15 min, 5-20 min, and 15-30 min p.i., and kinetic analysis was performed. TBRmax values and kinetic analysis were correlated with histological classification. ROC analyses were performed for each time frame and sensitivity, specificity, and accuracy were assessed. RESULTS: TBRmax values in the earlier summation images were significantly better for tumour grading (P < 0.001) when compared to standard 20-40 min scans, with best results for the early 5-15 min scan. This was due to higher TBRmax in the HGG (3.9 vs. 3.3; p < 0.001), while TBRmax remained nearly stable in the LGG (2.2 vs. 2.1). Overall, accuracy increased from 70 % in the 20-40 min analysis to 77 % in the 5-15 min images, but did not reach the accuracy of dynamic analysis (80 %). CONCLUSIONS: Early TBRmax assessment (5-15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20-40 min p.i.) mainly caused by the characteristic high (18)F-FET uptake of HGG in the initial phase. Therefore, when dynamic (18)F-FET-PET cannot be performed, early TBRmax assessment can be considered as an alternative for tumour grading. PMID- 26666241 TI - The infections of Saint-Louis: possible involvement of malaria. PMID- 26666242 TI - Utilization of cervical cancer screening services and its associated factors among primary school teachers in Ilala Municipality, Dar es Salaam, Tanzania. AB - BACKGROUND: Worldwide cervical cancer is one of the more common forms of carcinoma among women, causing high morbidity and high mortality. Despite being a major health problem in Tanzania, screening services for cervical cancer are very limited, and uptake of those services is low. We therefore conducted a study to investigate utilization of cancer screening services, and its associated factors among female primary school teachers in Ilala Municipality, Dar es Salaam. METHOD: We conducted a cross-sectional study between May - August 2011 which involved 110 primary schools in Ilala Municipality in Dar es Salaam. Five hundred and twelve female primary school teachers were sampled using a two-stage cluster sampling procedure. Data on utilization of cervical cancer and risk factors were collected using a self-administered questionnaire. Proportional utilization of cervical cancer screening services was identified through a self report. Risk factors for services utilization were assessed using logistic regression analyses. RESULTS: Out of 512 female primary school teachers, only 108 (21 %) reported to ever been screened for cervical cancer. Utilization of cervical cancer screening services was 28 % among those aged 20-29, 22 % among married and 24 % among those with higher level of education. Women were more likely to utilize the cancer-screening service if they were multiparous (age-adjusted OR = 3.05, 95 % CI 1.15-8.06, P value 0.025), or reported more than one lifetime sexual partner (age-adjusted OR 2.17, 95 % CI 1.04-4.54, P value 0.038), or did not involve their spouse in making health decisions (adjusted OR 3.56, 95 % CI 2.05-6.18, P value <0.001). CONCLUSION: The study has demonstrated low level of utilization of cervical cancer screening service among female primary school teachers in Ilala munipality. Female primary school teachers with more than one previous pregnancy and those with more than one life-time sex partners were more likely to report utilization of the service. Spouse or partners support was an important factor in the utilization of cervical cancer screening service amongst the study population. PMID- 26666243 TI - Next-generation sequencing using a pre-designed gene panel for the molecular diagnosis of congenital disorders in pediatric patients. AB - BACKGROUND: Next-generation sequencing (NGS) has revolutionized genetic research and offers enormous potential for clinical application. Sequencing the exome has the advantage of casting the net wide for all known coding regions while targeted gene panel sequencing provides enhanced sequencing depths and can be designed to avoid incidental findings in adult-onset conditions. A HaloPlex panel consisting of 180 genes within commonly altered chromosomal regions is available for use on both the Ion Personal Genome Machine (PGM) and MiSeq platforms to screen for causative mutations in these genes. METHODS: We used this Haloplex ICCG panel for targeted sequencing of 15 patients with clinical presentations indicative of an abnormality in one of the 180 genes. Sequencing runs were done using the Ion 318 Chips on the Ion Torrent PGM. Variants were filtered for known polymorphisms and analysis was done to identify possible disease-causing variants before validation by Sanger sequencing. When possible, segregation of variants with phenotype in family members was performed to ascertain the pathogenicity of the variant. RESULTS: More than 97% of the target bases were covered at >20*. There was an average of 9.6 novel variants per patient. Pathogenic mutations were identified in five genes for six patients, with two novel variants. There were another five likely pathogenic variants, some of which were unreported novel variants. CONCLUSIONS: In a cohort of 15 patients, we were able to identify a likely genetic etiology in six patients (40%). Another five patients had candidate variants for which further evaluation and segregation analysis are ongoing. Our results indicate that the HaloPlex ICCG panel is useful as a rapid, high throughput and cost-effective screening tool for 170 of the 180 genes. There is low coverage for some regions in several genes which might have to be supplemented by Sanger sequencing. However, comparing the cost, ease of analysis, and shorter turnaround time, it is a good alternative to exome sequencing for patients whose features are suggestive of a genetic etiology involving one of the genes in the panel. PMID- 26666244 TI - A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer. AB - BACKGROUND: KRAS mutations are clinically important predictors of resistance to EGFR-directed therapies in colorectal cancer (CRC). Oncogenic activation of the RAS/RAF/MEK/ERK signaling cascade mediates proliferation independent of growth factor signaling. We hypothesized that targeting MEK with selumetinib could overcome resistance to cetuximab in KRAS mutant CRC. METHODS: A phase I study (NCT01287130) was undertaken to determine the tolerability, and pharmacokinetic profiles of the combination of selumetinib and cetuximab, with an expanded cohort in KRAS-mutant CRC. RESULTS: 15 patients were treated in the dose escalation cohort and 18 patients were treated in the expansion cohort. Two dose-limiting toxicities were observed. One grade 3 acneiform rash and one grade 4 hypomagnesemia occurred. The most common grade 1 and 2 adverse events included rash, nausea/vomiting, diarrhea, and fatigue. The maximum tolerated dose was established at selumetinib 75 mg p.o. BID and cetuximab 250 mg/m(2) weekly following a 400 mg/m(2) load. Best clinical response in the dose escalation group included 1 unconfirmed partial response in a patient with CRC and stable disease (SD) in 5 patients (1 squamous cell carcinoma of the tonsil, 1 non-small cell lung cancer, and 3 CRC), and in the KRAS-mutant CRC dose expansion cohort, of the 14 patients who were evaluable for response, 5 patients had SD and 9 patients had progressive disease. CONCLUSIONS: The combination of selumetinib and cetuximab is safe and well tolerated. Minimal anti-tumor activity was observed in KRAS-mutant refractory metastatic CRC. Further investigations might be warranted in other cancer subtypes. PMID- 26666245 TI - Up-Regulation of Voltage Gated K+ Channels Kv1.3 and Kv1.5 by Protein Kinase PKB/Akt. AB - BACKGROUND: The voltage gated K+ channels Kv1.3 and Kv1.5 contribute to the orchestration of cell proliferation. Kinases participating in the regulation of cell proliferation include protein kinase B (PKB/Akt). The present study thus explored whether PKB/Akt modifies the abundance and function of Kv1.3 and Kv1.5. METHODS: Kv1.3 or Kv1.5 was expressed in Xenopus laevis oocytes with or without wild-type PKB/Akt, constitutively active T308D/S473DPKB/Akt or inactive T308A/S473APKB/Akt. The channel activity was quantified utilizing dual electrode voltage clamp. Moreover, HA-tagged Kv1.5 protein was determined utilizing chemiluminescence. RESULTS: Voltage gated K+ currents were observed in Kv1.3 or Kv1.5 expressing oocytes but not in water-injected oocytes or in oocytes expressing PKB/Akt alone. Co-expression of PKB/Akt or T308D/S473DPKB/Akt, but not co-expression of T308A/S473APKB/Akt significantly increased the voltage gated current in both Kv1.3 and Kv1.5 expressing oocytes. As shown for Kv1.5, co expression of PKB/Akt enhanced the channel protein abundance in the cell membrane. In Kv1.5 expressing oocytes voltage gated current decreased following inhibition of carrier insertion by brefeldin A (5 uM) to similarly low values in the absence and presence of PKB/Akt, suggesting that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane. CONCLUSION: PKB/Akt up-regulates both, Kv1.3 and Kv1.5 K+ channels. PMID- 26666246 TI - Impaired PLP-dependent metabolism in brain samples from Huntington disease patients and transgenic R6/1 mice. AB - Oxidative stress has been described as important to Huntington disease (HD) progression. In a previous HD study, we identified several carbonylated proteins, including pyridoxal kinase and antiquitin, both of which are involved in the metabolism of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6. In the present study, pyridoxal kinase levels were quantified and showed to be decreased both in HD patients and a R6/1 mouse model, compared to control samples. A metabolomic analysis was used to analyze metabolites in brain samples of HD patients and R6/1 mice, compared to control samples using mass spectrometry. This technique allowed detection of increased concentrations of pyridoxal, the substrate of pyridoxal kinase. In addition, PLP, the product of the reaction, was decreased in striatum from R6/1 mice. Furthermore, glutamate and cystathionine, both substrates of PLP-dependent enzymes were increased in HD. This reinforces the hypothesis that PLP synthesis is impaired, and could explain some alterations observed in the disease. Together, these results identify PLP as a potential therapeutic agent. PMID- 26666247 TI - UGT1A1*28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study. AB - BACKGROUND: Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. OBJECTIVES: To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. METHODS: This is a cohort study of 1,354 very preterm infants (gestational age <32 weeks) born in Jutland, Denmark in 1997 2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD). RESULTS: Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76 0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p < 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results. CONCLUSIONS: Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns. PMID- 26666248 TI - Breaking Out of Surveillance Silos: Integrative Geospatial Data Collection for Child Injury Risk and Active School Transport. AB - The preponderance of active school transport (AST) and child injury research has occurred independently, yet they are inherently related. This is particularly true in urban areas where the environmental context of AST may pose risks to safety. However, it can be difficult to make these connections due to the often segregated nature in which these veins of research operate. Spatial video presents a geospatial approach for simultaneous data collection related to both issues. This article reports on a multi-sector pilot project among researchers, a children's hospital, and a police department, using spatial video to map child AST behaviors; a geographic information system (GIS) is used to analyze these data in the environmental context of child pedestrian injury and community violence. PMID- 26666249 TI - Socio-Urban Spatial Patterns Associated with Dyslipidemia among Schoolchildren in the City of San Luis Potosi, Mexico. AB - The places where a child lives and attends to school are both major environmental and social determinants of its present and future health status. Noncommunicable diseases (NCDs) and some of their risk factors among child and adolescent populations are obesity and dyslipidemia, so finding the patterns of distribution of these risk factors by gender, type of school, area, and margination level is important to do health intervention focusing in their necessities to prevent diseases at younger ages. Because of that, a cross-sectional study was performed among elementary and junior high school students from public and private schools in six of the seven areas of the metropolitan zone of San Luis Potosi, Mexico. Biochemical dyslipidemia indicators (triglycerides, total cholesterol, and high density lipoprotein) and anthropometric data (weight and height) were obtained. Seventeen public schools and five private schools with a total of 383 students were included. More than half of the studied population (53.0%) had elevated triglyceride levels. A total of 330 students (86.2%) had normal levels of total cholesterol with a mean value of 141.7 mg/dl, and 202 schoolchildren (52.8%) had lower than acceptable levels of high-density lipoprotein (HDL) with a mean value of 43.9 mg/dl. There were differences in the levels of high-density protein between the areas and the type of school where they had been studied. Finally, a total of 150 students (39.4%) had at least one altered lipid value and 103 participants (26.9%) had two altered values. Several students, despite their young age, showed a high prevalence of risk factors, so it is important to design programs according to their necessities. PMID- 26666251 TI - Beacon of Hope? Lessons Learned from Efforts to Reduce Civilian Deaths from Police Shootings in an Australian State. AB - In the 1990s, the police service in Victoria, Australia, faced a crisis of community confidence due to a spate of civilian deaths from police shootings. In that decade, twice as many civilians died at the hands of the police in Victoria than in every other Australian state combined. Most of those killed were mentally ill and affected by drugs and alcohol, and were rarely a serious threat except to themselves. The problem was also almost entirely an urban phenomenon. Shootings in rural communities, where mentally ill people were more likely to be personally known to local police, were (and remain) almost unknown. The large number of fatalities was recognised as a serious threat to public confidence, and Victoria Police introduced a ground-breaking training programme, Operation Beacon. Operating procedures and weapons training were fundamentally changed, to focus on de-escalation of conflict and avoiding or minimising police use of force. In the short term, Operation Beacon was successful. Shooting incidents were dramatically reduced. However, during the first decade of the new century, the number of civilians being killed again increased. This article examines Operation Beacon, both as a successful model for reducing civilian deaths at the hand of police and as a cautionary tale for police reform. We argue that the lessons of Operation Beacon have been gradually forgotten and that old habits and attitudes resurfaced. Fatal shootings of mentally ill civilians can be prevented, but if success is to be other than temporary, the Beacon philosophy must be continually reemphasised by police management. PMID- 26666250 TI - Persisting Barriers to Employment for Recently Housed Adults with Mental Illness Who Were Homeless. AB - Adults with mental illness who are homeless experience multiple barriers to employment, contributing to difficulties securing and maintaining housing. Housing First programs provide quick, low-barrier access to housing and support services for this population, but their success in improving employment outcomes has been limited. Supported employment interventions may augment Housing First programs and address barriers to employment for homeless adults with mental illness. The present paper presents data from qualitative interviews to shed light on the persisting barriers to employment among people formerly homeless. Once housed, barriers to employment persisted, including the following: (1) worries about disclosing sensitive information, (2) fluctuating motivation, (3) continued substance use, and (4) fears about re-experiencing homelessness-related trauma. Nevertheless, participants reported that their experiences of homelessness helped them develop interpersonal strength and resilience. Discussing barriers with an employment specialist helps participants develop strategies to overcome them, but employment specialists must be sensitive to specific homelessness-related experiences that may not be immediately evident. Supported housing was insufficient to help people return to employment. Supported employment may help people return to work by addressing persisting barriers. PMID- 26666252 TI - Mitochondria: old and new target in brain research. PMID- 26666253 TI - Regional homogeneity alterations differentiate between tremor dominant and postural instability gait difficulty subtypes of Parkinson's disease. AB - Parkinson's disease (PD) can be classified into the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype, which present with different clinical courses and prognoses. However, the symptom-specific intrinsic neural mechanisms underlying the subtypes of PD still remain elusive. In the current study, we utilized resting-state fMRI (rs-fMRI) combined with the regional homogeneity (ReHo) method to investigate the modulations of neural activity in 13 patients with predominantly PIGD (p-PIGD) and 15 patients with predominantly TD (p-TD) in the resting state. Compared with healthy controls, the p-PIGD and the p-TD groups both displayed ReHo changes in the default mode network (DMN). By contrast, the p-TD group exhibited more ReHo alterations in the cerebellum involved in the cerebello-thalamo-cortical (CTC) loops, whilst the p PIGD group in extensive cortical and sub-cortical areas, including the frontal, parietal, occipital, temporal, limbic lobes, basal ganglia and thalamus, which are involved in the striatal-thalamo-cortical (STC) loops. Direct comparison between the two groups showed significant ReHo alterations in the primary visual cortex. Our findings underscore the differential involvement of the STC and CTC circuits underlying the two subtypes of PD. Moreover, relatively widespread neural activity abnormality, especially in the motor-related regions as well as the visual network, is apparently a characteristic feature of PIGD symptoms. This study could shed light on the underlying pathophysiology and clinical heterogeneity of PD presentation. PMID- 26666254 TI - Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1alpha hydroxycholecalciferol. AB - While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1alpha-hydroxycholecalciferol (1alpha-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1alpha-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1alpha-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1alpha-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1alpha-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1alpha (OH) D3 fed chicks. PMID- 26666255 TI - Clinic research on the treatment for humeral shaft fracture with minimal invasive plate osteosynthesis: a retrospective study of 128 cases. AB - INTRODUCTION: Minimal invasive plate osteosynthesis (MIPO) is one of the most important techniques in the treatment for humeral shaft fractures. This study was performed to evaluate the efficacy of MIPO technique for the treatment for humeral shaft fractures. MATERIALS AND METHODS: We retrospectively evaluated 128 cases with humeral shaft fractures that were treated with MIPO technique from March 2005 to August 2008. All the patients were followed up by routine radiological imaging and clinical examinations. Constant-Murley score and HSS elbow joint score were used to evaluate the treatment outcome. RESULTS: The average duration of the surgery was 60 min (range 40-95 min) without blood transfusion. All fractures healed without infection. All cases recovered carrying angle except four cases with 10 degrees -15 degrees cubitus varus. After the average follow-up of 23 (13-38) months, satisfactory function was achieved according to Constant-Murley score and HSS elbow joint score. Constant-Murley score was 80 on average (range 68-91). According to HSS elbow joint score, there were 123 cases of excellent clinical outcome and five cases of effective outcome. CONCLUSION: It seems to be a safe and effective method for managing humeral shaft fractures with MIPO technique. PMID- 26666257 TI - Acid attack victims should have same rights as disabled people, Indian Supreme Court rules. PMID- 26666256 TI - 5th International ACC Symposium: An Outlook to Current and Future Research on the Biology of Adrenocortical Carcinoma: Diagnostic and Therapeutic Applications. AB - Groundbreaking progress has been recently made in elucidating the signaling pathways that are altered in adrenocortical carcinoma (ACC), an endocrine malignancy that still has an unfavorable prognosis, and in understanding its genomic structure. These advances need now to be translated to create cellular and animal models more relevant to human disease in order to develop new and more effective diagnostic procedures and targeted therapies against this deadly malignancy. PMID- 26666258 TI - Placebo-controlled study in neuromyelitis optica-Ethical and design considerations. AB - BACKGROUND: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. OBJECTIVE: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity. METHODS: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. RESULTS: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. CONCLUSION: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path. PMID- 26666260 TI - Lipids and lipoproteins and inflammatory markers in patients with chronic apical periodontitis. AB - BACKGROUND: Since chronic apical periodontitis (CAP) appears to be a risk factor for coronary heart disease, the aim of the study was to determine the relationship between the size of CAP lesion and inflammatory markers (hsCRP, IL 6, TNF-alpha), as well as lipids and lipoproteins (LpPLA2, apoAI, apoB level) in blood serum of patients with CAP. METHODS: The patients studied (n = 43) were divided into groups: patients under 50 and over 50 years of age, and a separate subgroup of the oldest age with the largest size of CAP lesions. Apolipoprotein AI (apoAI) above 150 mg/dL and below 150 mg/dL was used as an important criterion for the division of patients into groups. The CAP lesion size was measured using the Kodak digital imaging system software. The control group consisted of clinically healthy volunteers (n = 20) without CAP. Lipids were measured on a Siemens analyzer (Germany), apoAI, apoB, hsCRP levels were determined by immunonephelometric method, using the Health Care Diagnostic Product (Siemens GmbH, Germany), and IL-6, TNF-alpha and LpPLAG7 assay kits (ELISA, R&D Systems) were used. RESULTS: The findings suggested that in patients with CAP and their age increase, the CAP lesion size, the concentration of inflammatory markers and LpPLA2 mass increased. Correlations between the CAP lesion size and LpPLA2 mass and between the CAP lesion size and TG level in patients with apoAI 150 <= mg/dL showed increase TG in atherogenic apoB-containing triglyceride-rich lipoprotein and TC in cholesterol-rich lipoprotein. The patients with a low apoAI and high LpPLA2 level can have a higher risk of odontogenic disease and progression of atherosclerosis and coronary heart disease. CONCLUSION: We have found a positive correlation between apoAI level and the CAP lesion size and a negative correlation between LpPLA2 level and the CAP lesion size. The results suggest that apoAI and LpPLA2 in HDL particles have antiinflammatory action and together can limit the CAP lesion size in patient with a higher apoAI level. The literature data on the distribution of lipoprotein particles in subjects are still insufficient, so this problem requires further studies. PMID- 26666263 TI - A concept analysis of children's agency within the health literature. AB - The capacity of children to act as agents is being increasingly recognized and has important implications for health research and practice. However, there are various discrepancies in how children's agency is defined in the literature. The aim of this analysis was to examine the concept of children's agency within the health-related literature, using Rodgers evolutionary method. The following questions were addressed: How did the concept of agency become associated with children in the health-related literature? What are the sociocultural and legal contexts that surround the concept of children's agency? What is the meaning of children's agency? Forty-five articles were included in the analysis. An inductive approach was used to identify the attributes of children's agency as well as the temporal, disciplinary, and paradigmatic trends in its conceptualization. The concept of children's agency first appeared in the health literature in the 1980s and was defined as an ability children could gradually develop. Later on, children's agency was used to refer to the capacity of all children to influence their own and others' health-care needs and is now increasingly used to refer to children as active agents who reflect on and construct their social worlds. PMID- 26666259 TI - US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. AB - Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition. PMID- 26666262 TI - Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles. AB - t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO-driven mouse models of leukemia with the mutational profiles of human AML patients. We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo. This integrative genetic profiling approach allowed us to accurately predict cooperating events in t(8;21)(+) AML in a robust and unbiased manner, while also revealing functional convergence in mouse and human AML. PMID- 26666264 TI - When Developmental Delay and Failure to Thrive Are Not Psychosocial. PMID- 26666261 TI - A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. AB - Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igkappa exons promote exon-skipping and synthesis of V domain-less kappa light chains (DeltaV-kappaLCs). Unexpectedly, such DeltaV-kappaLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding DeltaV-kappaLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of DeltaV-kappaLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing DeltaV-kappaLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. DeltaV-kappaLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing DeltaV-kappaLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igkappa alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with DeltaV-kappaLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. PMID- 26666265 TI - Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension. AB - OBJECTIVE: This study had 2 goals: (1) to identify clinical and demographic characteristics associated with sildenafil exposure for infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH); and (2) to characterize hospital-specific treatment frequency, age at first administration, and length of sildenafil treatment. METHODS: This retrospective cohort study used data from the Pediatric Health Information System to determine variables associated with sildenafil exposure and between-hospital variations in sildenafil utilization patterns. The study included infants with BPD-PH who were discharged between January 1, 2006, and December 31, 2013. RESULTS: Within 36 US pediatric hospitals, 3720 infants were diagnosed with BPD, of whom 598 (16%) also had a diagnosis of PH (BPD-PH). Among infants with BPD-PH, 104 infants (17%) received sildenafil. The odds for sildenafil treatment among infants born between 25 and 26 weeks' gestational age (GA) and <24 weeks' GA, respectively, were 2.26 (95% confidence interval [CI]: 1.20-4.24) and 3.21 (95% CI: 1.66-6.21) times those of infants born at 27 to 28 weeks' GA. Severity of BPD correlated with sildenafil exposure, with adjusted odds ratios (ORs) for moderate BPD (OR: 3.03 [95% CI: 1.03-8.93]) and severe BPD (OR: 7.56 [95% CI: 2.50-22.88]), compared with mild BPD. Greater rates of sildenafil exposure were observed among small for GA neonates (OR: 2.32 [95% CI: 1.21-4.46]). The proportion of infants with BPD-PH exposed to sildenafil varied according to hospital (median: 15%; 25th-75th percentile: 0%-25%), as did the median duration of therapy (52 days; 25th-75th percentile: 28-109 days). CONCLUSIONS: The odds of sildenafil treatment were greatest among the most premature infants with severe forms of BPD. The frequency and duration of sildenafil exposure varied markedly according to institution. Patient-centered trials for infants with BPD-PH are needed to develop evidence based practices. PMID- 26666266 TI - Commentary: Harnessing the Fragility of Pain Memories to Help Children Forget: A New Avenue for Pediatric Psychology Interventions? PMID- 26666267 TI - Children's Forgetting of Pain-Related Memories. AB - OBJECTIVE: Given that forgetting negative experiences can help children cope with these experiences, we examined their ability to forget negative aspects of painful events. METHODS: 86 children aged 7-15 years participated in a retrieval induced forgetting task whereby they repeatedly retrieved positive details of a physically painful experience, and an experimental pain task (cold-pressor task). RESULTS: Repeatedly retrieving positive details of a prior pain experience produced forgetting of the negative aspects of that experience. Pain-related self efficacy predicted retrieval-induced forgetting; children with a poorer belief in their ability to cope with pain experienced less forgetting. Children who had a more difficult time forgetting prior negative experiences were more anxious about the pain task and reported higher pain thresholds. CONCLUSIONS: Understanding children's memory for painful experiences may help improve their pain management and coping ability. PMID- 26666268 TI - CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. AB - CHCHD10-related diseases include mitochondrial DNA instability disorder, frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) clinical spectrum, late-onset spinal motor neuropathy (SMAJ), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we show that CHCHD10 resides with mitofilin, CHCHD3 and CHCHD6 within the "mitochondrial contact site and cristae organizing system" (MICOS) complex. CHCHD10 mutations lead to MICOS complex disassembly and loss of mitochondrial cristae with a decrease in nucleoid number and nucleoid disorganization. Repair of the mitochondrial genome after oxidative stress is impaired in CHCHD10 mutant fibroblasts and this likely explains the accumulation of deleted mtDNA molecules in patient muscle. CHCHD10 mutant fibroblasts are not defective in the delivery of mitochondria to lysosomes suggesting that impaired mitophagy does not contribute to mtDNA instability. Interestingly, the expression of CHCHD10 mutant alleles inhibits apoptosis by preventing cytochrome c release. PMID- 26666270 TI - Practical considerations in the management of proton-pump inhibitors. AB - Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy. PMID- 26666271 TI - Choline Chloride Catalyzed Amidation of Fatty Acid Ester to Monoethanolamide: A Green Approach. AB - Choline chloride catalyzed efficient method for amidation of fatty acid methyl ester to monoethanolamide respectively. This is a solvent free, ecofriendly, 100% chemo selective and economically viable path for alkanolamide synthesis. The Kinetics of amidation of methyl ester were studied and found to be first order with respect to the concentration of ethanolamine. The activation energy (Ea) for the amidation of lauric acid methyl ester catalyzed by choline chloride was found to be 50.20 KJ mol(-1). The 98% conversion of lauric acid monoethanolamide was obtained at 110 degrees C in 1 h with 6% weight of catalyst and 1:1.5 molar ratio of methyl ester to ethanolamine under nitrogen atmosphere. PMID- 26666269 TI - Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment naive and bevacizumab-resistant glioblastoma. AB - Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti-angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin-2 (Ang-2) as a potential target in both naive and bevacizumab-treated glioblastoma. Ang-2 expression was absent in normal human brain endothelium, while the highest Ang-2 levels were observed in bevacizumab-treated GBM. In a murine GBM model, VEGF blockade resulted in endothelial upregulation of Ang-2, whereas the combined inhibition of VEGF and Ang-2 leads to extended survival, decreased vascular permeability, depletion of tumor-associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. CD206(+) (M2-like) macrophages were identified as potential novel targets following anti-angiogenic therapy. Our findings imply a novel role for endothelial cells in therapy resistance and identify endothelial cell/myeloid cell crosstalk mediated by Ang-2 as a potential resistance mechanism. Therefore, combining VEGF blockade with inhibition of Ang-2 may potentially overcome resistance to bevacizumab therapy. PMID- 26666272 TI - Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids. AB - The present study describes the synthesis, characterization and evaluation of antiproliferative activity of novel diisopropylphenyl esters of alpha-linolenic acid (ALA), valproic acid (VA), butyric acid (BA) and 2-ethylhexanoic acid (2 EHA). These esters were chemically synthesized by the esterification of fatty acids with 2,6-diisopropylphenol and 2,4-diisopropylphenol (propofol). The structure of new conjugates viz. propofol-(alpha-linolenic acid) (2,6P-ALA and 2,4P-ALA), propofol-valproic acid (2,6P-VA and 2,4P-VA), propofol-butyric acid (2,6P-BA and 2,4P-BA) and propofol-(2-ethylhexanoic acid) (2,6P2-EHA and 2,4P-2 EHA) were characterized by FT-IR, NMR ((1)H, (13)C) and mass spectral data. The synthesized conjugates having more lipophilic character were tested for antiproliferative in vitro studies on A549, MDA-MB-231, HeLa, Mia-Pa-Ca and HePG2 cancer cell lines. All the conjugates showed specific growth inhibition on studied cancer cell lines. Among the synthesized esters, the conjugates synthesized from BA, VA and 2-EHA exhibited prominent growth inhibition against A549, HeLa, Mia-Pa-Ca and HePG2 cancer cell lines. The preliminary results suggest that the entire novel conjugates possess antiproliferative properties that reduce the proliferation of cancer cells in vitro. PMID- 26666273 TI - Chemical Composition and Characteristic Odor Compounds in Essential Oil from Alismatis Rhizoma (Tubers of Alisma orientale). AB - Chemical composition and potent odorants that contribute to the characteristic odor of essential oil from Alismatis Rhizoma (tubers of Alisma orientale) were investigated by gas chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC O), aroma extract dilution analysis (AEDA) and relative flavor activity (RFA) methods. Fifty components, representing 94.5% of the total oil, were identified. In this study, we newly identified thirty-nine compounds in the oil from tubers of A. orientale. The major constituents of the essential oil were khusinol (36.2%), delta-elemene (12.4%), germacron (4.1%), alismol (3.8%), beta-elemene (3.1%), and alpha-bisabolol (1.9%). Through sensory analysis, sixteen aroma active compounds were detected and the key contributing aroma-active compounds were delta-elemene (woody, flavor dilution (FD)-factor = 4, RFA = 0.3) beta elemene (spicy, FD = 5, RFA = 0.7), spathulenol (green, FD = 5, RFA = 1.0), gamma eudesmol (woody, FD = 6, RFA = 1.5), and gamma-cadinol (woody, FD = 5, RFA = 1.0). These compounds are thought to contribute to the odor from tubers of A. orientale. These results imply that the essential oil from the tubers of A. orientale deserve further investigations in the phytochemical and medicinal fields. PMID- 26666274 TI - Preparation of Nonionic Vesicles Using the Supercritical Carbon Dioxide Reverse Phase Evaporation Method and Analysis of Their Solution Properties. AB - We have previously reported a new preparation method for liposomes using supercritical carbon dioxide (scCO2) as a solvent, referred to as the supercritical carbon dioxide reverse phase evaporation (scRPE) method. In our previous work, addition of ethanol to scCO2 as a co-solvent was needed, because lipid molecules had to be dissolved in scCO2 to form liposomes. In this new study, niosomes (nonionic surfactant vesicles) were prepared from various nonionic surfactants using the scRPE method. Among the nonionic surfactants tested were polyoxyethylene (6) stearylether (C18EO6), polyoxyethylene (5) phytosterolether (BPS-5), polyoxyethylene (6) sorbitan stearylester (TS-106V), and polyoxyethylene (4) sorbitan stearylester (Tween 61). All these surfactants have hydrophilic-lipophilic balance values (HLBs) around 9.5 to 9.9, and they can all form niosomes using the scRPE method even in the absence of ethanol. The high solubility of these surfactants in scCO2 was shown to be an important factor in yielding niosomes without ethanol addition. The niosomes prepared with the scRPE method had higher trapping efficiencies than those prepared using the conventional Bangham method, since the scRPE method gives a large number of unilamellar vesicles while the Bangham method gives multilamellar vesicles. Polyoxyethylene-type nonionic surfactants with HLB values from 9.5 to 9.9 were shown to be optimal for the preparation of niosomes with the scRPE method. PMID- 26666275 TI - Effects of Added Salts on Surface Tension and Aggregation of Crown Ether Surfactants. AB - Two crown ether surfactants, dodecanoyloxymethyl- (C11Phi6) and octanoyloxymethyl 18-crown-6 (C7Phi6), were synthesized and the surface tension dependence on surfactant concentration of their aqueous solutions was measured both in the absence and presence of alkali chlorides to confirm the critical micelle concentration (CMC) is highest for the added cation that have an ionic diameter comparable to the hole size of the crown ether ring and that several break points on the surface tension vs. concentration curves occur for these crown ether surfactants. For C11Phi6 and C7Phi6, in the absence of salt, the surface tension vs. concentration curves had two break points. Using the solubilization of a water-insoluble dye as an indicator, we found that the break point at the higher concentration (m0) for C7Phi6 was due to micelle formation. Two break points were also observed for the aqueous solution of C11Phi6 in the presence of NaCl, KCl, RbCl, and CsCl salts at concentrations of 0.22 mol kg(-1) and for C7Phi6 with 0.22 mol kg(-1) KCl added. The CMC (m0) was found to be the highest for solutions containing K(+) salts because K(+) has an ionic diameter comparable to the hole size of 18-crown-6 ring. Furthermore, the CMC decreased as the ionic diameters of the added cations deviated from the hole size. The molecular areas at two break points, estimated by the Gibbs adsorption isotherm, except for that at the break point at mI of C7Phi6, were very small for an adsorbed monolayer. Further investigation is required to elucidate the reason for the break point at mI. PMID- 26666276 TI - Interactions between Carbon Nanomaterials and Biomolecules. AB - Interactions between carbon nanomaterials, including carbon dots, fullerene, carbon nanotube, graphene, and graphene oxide, and biomolecules play an important role in the field of nanobiotechnology. Due to the unique properties of carbon nanomaterials and the magnificent features of their colloids, it shows high potential in fibrillation inhibition, high sensitivity sensor fabrication, bioimaging, drug delivery, and other areas. Hereby, we will go over different families of carbon nanomaterials regarding to the interaction between carbon nanomaterials and biomolecules at the interface, and their applications will be reviewed as well. PMID- 26666277 TI - [Not Available]. PMID- 26666278 TI - [Cost-effective medical therapy of hepatitis C employing novel compensation models - pay for cure]. AB - Direct acting antivirals (DAAs) have increased cure rates for chronic hepatitis C infection up to nearly 100 %. At the same time treatment costs have risen significantly. Treating all HCV infected patients in Germany with DAAs would generate medication costs ranging between 19 and 37 billion EUR depending on the drug regimen used. Expenses in patients who fail to respond to treatment would amount to approximately 0.9 to 2.15 billion EUR. In difficult to treat patient populations that are characterized by prior failure to treatment or advanced liver disease, lost drug expenses are particularly high due to lower cure rates and longer treatment duration. Outcome-based reimbursement schemes are used to improve the quality of care and to reduce costs in the health care system. In Germany, disease management programs have been implemented for defined chronic diseases. However, drug reimbursement is still based on packages sold (pay for pill). In this context, it would be appealing to link reimbursement and treatment success (pay for cure) in order to reward successful treatment, limit lost drug spending and develop a shared risk environment that would involve all concerned parties. Under the assumption that 20,000 patients with HCV are treated each year in Germany and that cure rates are 95.4 %, the saved treatment costs would amount up to 45 and 107 million EUR per year. By this approach, economic incentives to withhold therapy from difficult to treat patients could be avoided. PMID- 26666279 TI - [Resection of small colorectal polyps using a dedicated cold resection snare]. AB - BACKGROUND: According to actual German guidelines the resection of small colorectal polyps can be performed using a biopsy forceps. The guidelines recommend surveillance colonoscopy within 2 - 6 months if complete resection cannot be prooven. Cold snare resection of polyps allows easy and complete resection of small and diminutive polyps. AIM OF THE STUDY: To develop and evaluate a snare for cold resections of colorectal polyps. METHODS: We conducted a monocentric observational trial in our university hospital to test the performance of the cold snare resection for colorectal polyps < 10 mm. Consecutive patients were enrolled in the study. No submucosal injection was performed. Polyps were grasped with the snare and after accurate positioning of the snare polyps were resected. Primary endpoint was the rate of complete resection as defined by histology. Complications such as bleeding, perforation or abdominal pain were recorded. RESULTS: In total 99 polyps were resected in 58 patients (15 female, 43 male, age 62.8 years (31 - 85 years). The mean polyp size was 5.3 mm (2 - 10 mm). Of the 99 polyps 88 were adenoma (74 tubular adenomas, 4 tubulo-villous adenoma and 2 serrated adenoma), 18/99 polys were hyperplastic polyps and one polyp revealed as a leiomyoma. In total 74 adenoma (92.5 %) were completely resected en bloc. In polyps of 1 - 4 mm of size the R0 resection rate was 90 % (27/30). In polyps of 5 - 10 mm of size the R0 resection rate was 94 % (47/50). No complications occurred. DISCUSSION: This study demonstrated a high R0 Resection rate for small colorectal polyps using a dedicated cold resection snare. Cold snare resection of small polyps helps to reduce the rate of piece meal resections in small colorectal polyps. PMID- 26666280 TI - Beyond fibrosis: stellate cells as liver stem cells. AB - The high regenerative potential of the liver is driven by parenchymal and non parenchymal cells, which restore the original liver mass after injury by cell proliferation. The contribution of stem- and progenitor cells to liver regeneration is mainly observed when hepatocyte proliferation is impaired. However, the origin of stem/progenitor cells and their effectivity to restore injured liver is currently discussed controversially. Hepatic stellate cells, which are mainly known for their contribution to fibrosis in chronic liver diseases, were recently identified as mesenchymal stem cells (MSC) of the liver. Stellate cells are also involved in liver regeneration and fulfill a dual function by supporting neighboring cells and developing into liver epithelial cells. This demonstrates that stellate cells not only exhibit the same expression profile and differentiation potential but also functional similarities to MSC of other organs, which are at present intensively studied by many groups for their therapeutic use in liver diseases. PMID- 26666281 TI - Balancing viral replication in spleen and liver determines the outcome of systemic virus infection. AB - The innate immune system limits virus replication during systemic infection by producing type I interferons (IFN-I) but still has to allow viral replication to achieve maximal innate and adaptive immune activation. Some spleen and lymph node resident antigen presenting cells (APCs) show limited response to IFN-I due to expression of the endogenous inhibitor of IFN-I signaling, Usp18. Therefore, virus in this spleen niche replicates despite high levels of IFN-I. This enforced viral replication leads to an exorbitant propagation of viral antigens and viral RNA. Viral antigen leads to massive activation of the adaptive immune system, while viral RNA to activated innate immunity. In contrast to these APCs, liver resident Kupffer cells, take up most of the systemic virus and suppress its replication in response to IFN-I. In addition, virus specific CD8 + T cells which are primed in the spleen migrate to the liver and kill virus infected cells. In this review we discuss the different mechanisms, which influence immune activation in spleen and antiviral mechanisms in the liver and how they determine the outcome of virus infection. PMID- 26666282 TI - Genetic variants in adult liver diseases. AB - In the last decades, understanding of genetic variants contributing to liver disease development has considerably improved through novel genotyping techniques. Genetic variants of single genes are known to be decisive for the development of monogenetic liver diseases of varying severity. Identification of genetic variants is an important part of the diagnostic process, e. g. the majority of patients with high iron [Fe] (HFE)-associated hemochromatosis carry the homozygous mutation p.C282Y. Detection of mutations in genes encoding hepatobiliary transport proteins like familial intrahepatic cholestasis 1 (FIC1), bile salt export pump (BSEP), or multidrug resistance protein 3 (MDR3) is the basis to differentiate various forms of intrahepatic cholestasis. Moreover, genetic variants in a variety of genes are known to act as disease modifiers and represent risk factors for disease progression and the development of cirrhosis or even hepatocellular carcinoma. Success of drug treatment or appearance of severe side effects can also be influenced by specific genetic variants. All these aspects underscore the increasing importance of genetic variants, which in the future may help to identify patients at risk for disease progression or help to guide treatment decisions. In the present overview, specific frequent genetic variants are summarized that play roles in monogenetic liver diseases, forms of intrahepatic cholestasis, gallstone development, fatty liver disease, drug induced liver injury, and liver disease progression as well as hepatocellular carcinoma development. PMID- 26666284 TI - [S2k guideline: quality requirements for gastrointestinal endoscopy, AWMF registry no. 021-022]. PMID- 26666283 TI - English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis. AB - Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy. PMID- 26666286 TI - MID Max: LC-MS/MS Method for Measuring the Precursor and Product Mass Isotopomer Distributions of Metabolic Intermediates and Cofactors for Metabolic Flux Analysis Applications. AB - The analytical challenges to acquire accurate isotopic data of intracellular metabolic intermediates for stationary, nonstationary, and dynamic metabolic flux analysis (MFA) are numerous. This work presents MID Max, a novel LC-MS/MS workflow, acquisition, and isotopomer deconvolution method for MFA that takes advantage of additional scan types that maximizes the number of mass isotopomer distributions (MIDs) that can be acquired in a given experiment. The analytical method was found to measure the MIDs of 97 metabolites, corresponding to 74 unique metabolite-fragment pairs (32 precursor spectra and 42 product spectra) with accuracy and precision. The compounds measured included metabolic intermediates in central carbohydrate metabolism and cofactors of peripheral metabolism (e.g., ATP). Using only a subset of the acquired MIDs, the method was found to improve the precision of flux estimations and number of resolved exchange fluxes for wild-type E. coli compared to traditional methods and previously published data sets. PMID- 26666287 TI - Hydrophilic Magnetofluorescent Nanobowls: Rapid Magnetic Response and Efficient Photoluminescence. AB - Multifunctional integration based on a single nanostructure is emerging as a promising paradigm to future functional materials. In this paper, novel magnetofluorescence nanobowls built with ferroferric mandrel and quantum dots exoderm is reported. Magnetic mandrels are stacked into nanobowls though hydrophobic primary Fe3O4 nanocrystals dragged into anion polyelectrolyte aqueous solution via forced solvent evaporation. Bright luminescence core/shell/shell CdSe/CdS/ZnS quantum dots (QDs) are modified with cationic hyperbranched polyethylenimine (PEI). Through electrostatic interactions, positively charged PEI-coated QDs are anchored on the surface of magnetic mandrel. Under this method, the luminescence of QDs is not quenched by magnetic partners in the resultant magnetoflurescence nanobowls. Such magnetoflurescence nanobowls exhibit high saturation magnetization, superparamagnetic characteristics at room temperature, superior water dispersibility, and excellent photoluminescence properties. The newly developed magnetoflurescence nanobowls open a new dimension in efforts toward multimodal imaging probes combining strong magnetization and efficient fluorescence in tandem for biosensors and clinical diagnostic imaging. PMID- 26666285 TI - Perceived determinants of cardiovascular risk management in primary care: disconnections between patient behaviours, practice organisation and healthcare system. AB - BACKGROUND: Although conditions for high quality cardiovascular risk management in primary care in the Netherlands are favourable, there still remains a gap between practice guideline recommendations and practice. The aim of the current study was to identify determinants of cardiovascular primary care in the Netherlands. METHODS: We performed a qualitative study, using semi-structured interviews with healthcare professionals and patients with established cardiovascular diseases or at high cardiovascular risk. A framework analysis was used to cluster the determinants into seven domains: 1) guideline factors, 2) individual healthcare professional factors, 3) patient factors, 4) professional interaction, 5) incentives and recourses, 6) mandate, authority and accountability, and 7) social, political and legal factors. RESULTS: Twelve healthcare professionals and 16 patients were interviewed. Healthcare professionals and patients mentioned a variety of factors concerning all seven domains. Determinants of practice according to the health care professionals were related to communication between healthcare professionals, patients' lack of knowledge and self-management, time management, market mechanisms in the Dutch healthcare system and motivational interviewing skills of healthcare professionals. Patients mentioned determinants related to their knowledge of risk factors for cardiovascular diseases, medication adherence and self-management as key determinants. A key finding is the mismatch between healthcare professionals' and patients' views on patient's knowledge and self-management. CONCLUSIONS: Perceived determinants of cardiovascular risk management were mainly related to patient behaviors and (but only for health professionals) to the healthcare system. Though health care professionals and patients agree upon the importance of patients' knowledge and self-management, their judgment of the current state of knowledge and self-management is entirely different. PMID- 26666288 TI - Underuse of anticoagulation in patients with atrial fibrillation. AB - Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Guidelines recommend anticoagulation for patients with intermediate and high stroke risk (CHA2DS2-VASc score >= 2). Underuse of anticoagulants among eligible patients remains a persistent problem. Evidence demonstrates that the psychology of the fear of causing harm (omission bias) results in physicians' hesitancy to initiate anticoagulation and an inaccurate estimation of stroke risk. The American Heart Association (AHA) initiated the Get With The Guidelines-AFIB (GWTG-AFIB) module in June 2013 to enhance guideline adherence for treatment and management of AF. Better quality of care for AF patients can be provided by increasing adherence to anticoagulation guidelines and improving patient compliance with anticoagulation therapy through education and established protocols. Nonvitamin K antagonist oral anticoagulants may facilitate better patient adherence due to ease of administration and reduced monitoring burden. In this review, we discuss the reasons for underuse, omission bias contributing to underuse, and different strategies to address this issue. PMID- 26666290 TI - New regimens for intravenous acetylcysteine, where are we now? AB - Acetylcysteine has been used as a treatment for paracetamol overdose as a 20.25- or 21-h infusion for nearly 40 years. These regimens give 50% of the dose in the first 15 min or 1 h, and are associated with high rates of adverse reactions. A randomised controlled trial has demonstrated that a shorter (12 h) and simpler (two infusions) acetylcysteine regimen using a slower initial infusion rate produces lower rates of adverse events than the original 20.25-h regimen. However, this study was not sufficiently large to show therapeutic equivalence as a hepatoprotective therapy in paracetamol overdose. Two further studies are now reported, which also suggest lower rates of adverse reactions with lower initial rates of acetylcysteine administration. These modified regimens can now be accepted as better tolerated, but it is unlikely that a randomised study of sufficient size to demonstrate non-inferiority of any novel regimen would ever be funded. Against this background we suggest what can be done to establish the efficacy of these less toxic and potentially shorter alternative acetylcysteine regimens and to establish them into routine clinical use. PMID- 26666289 TI - Leveraging global gene expression patterns to predict expression of unmeasured genes. AB - BACKGROUND: Large collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes. RESULTS: We developed a greedy gene set selection (GGS) algorithm which returns a DM set of user specified size based on a specific correlation threshold (|rP|) and minimum number of DM genes that must be correlated to an unmeasured gene in order to infer the value of the unmeasured gene (redundancy). We evaluated GGS in the Cancer Genome Atlas (TCGA) HGSC data across 144 combinations of DM size, redundancy (1-3), and |rP| (0.60, 0.65, 0.70). Across the parameter sweep, GGS allows on average 9 times more gene expression information to be captured compared to the DM set alone. GGS successfully augments prognostic HGSC gene sets; the addition of 20 GGS selected genes more than doubles the number of genes whose expression is predictable. Moreover, the expression prediction is highly accurate. After training regression models for the predictable gene set using 2/3 of the TCGA data, the average accuracy (ranked correlation of true and predicted values) in the 1/3 testing partition and four independent populations is above 0.65 and approaches 0.8 for conservative parameter sets. We observe similar accuracies in the TCGA HGSC RNA sequencing data. Specifically, the prediction accuracy increases with increasing redundancy and increasing |rP|. CONCLUSIONS: GGS-selected genes, which maximize expression information about unmeasured genes, can be combined with candidate gene sets as a cost effective way to increase the amount of gene expression information obtained in large studies. This method can be applied to any organism, model system, disease, or tissue type for which whole genome gene expression data exists. PMID- 26666291 TI - Quantitative proteomics identifies 38 proteins that are differentially expressed in cucumber in response to cucumber green mottle mosaic virus infection. AB - BACKGROUND: Since it was first reported in 1935, Cucumber green mottle mosaic virus (CGMMV) has become a serious pathogen in a range of cucurbit crops. The virus is generally transmitted by propagation materials, and to date no effective chemical or cultural methods of control have been developed to combat its spread. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in an infected cucumber host, with the objective of elucidating the infection process and potential strategies to reduce both the economic and yield losses associated with CGMMV. METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC-MS/MS) were used to identify the differentially expressed proteins in cucumber plants infected with CGMMV compared with mock-inoculated plants. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions during CGMMV infection, while their in vivo expression was further verified by qPCR. RESULTS: Infection by CGMMV altered both the expression level and absolute quantity of 38 proteins (fold change >0.6) in cucumber hosts. Of these, 23 were found to be up regulated, while 15 were down-regulated. Gene ontology (GO) analysis revealed that 22 of the proteins had a combined function and were associated with molecular function (MF), biological process (BP) and cellular component (CC). Several other proteins had a dual function with 1, 7, and 2 proteins being associated with BP/CC, BP/MF, CC/MF, respectively. The remaining 3 proteins were only involved in MF. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 18 proteins that were involved in 13 separate metabolic pathways. These pathways were subsequently merged to generate three network diagrams illustrating the interactions between the different pathways, while qPCR was used to track the changes in expression levels of the proteins identified at 3 time points during CGMMV infection. Taken together these results greatly expand our understanding of the relationships between CGMMV and cucumber hosts. CONCLUSIONS: The results of the study indicate that CGMMV infection significantly changes the physiology of cucumbers, affecting the expression levels of individual proteins as well as entire metabolic pathways. The bioinformatic analysis also identified several pathogenesis-related (PR) proteins that could be useful in the development of disease-resistant plants. PMID- 26666292 TI - Sexual risk behaviors among HIV-patients receiving antiretroviral therapy in Southern Thailand: roles of antiretroviral adherence and serostatus disclosure. AB - The objective of this study was to examine the extent of unprotected sex among patients already established in HIV-medical care and their associated factors. Sexually active patients who were receiving antiretroviral therapy (ART) from five public hospitals in Trang province, Southern Thailand, were interviewed. Of 279 studied patients, 37.3% had unprotected sex in the prior 3 months and 27.2% did not disclose their serostatus to sexual partners. The median duration interquartile range (IQR) of using ART was 47 (27-60) months and 26.7% were non adherent to ART (i.e., taking less than 95% of the prescribed doses). More than one-third had the perception that ART use would protect against HIV transmission even with unprotected sex. About 36.6% reported that they were unaware of their current CD4 counts and nearly one-third did not receive any safe sex counseling at each medical follow-up. After adjustment for potential confounders, non adherence to ART and HIV-nondisclosure were strongly associated with an increase in the risk of unprotected sex with the adjusted odds ratio (aOR) of 5.03 (95% CI 2.68-9.44) and 3.89 (95% CI 1.57-9.61), respectively. In contrast, the risk for engaging in unprotected sex was less likely among patients having a negative serostatus partner (aOR = 0.30; 95% CI 0.12-0.75), a longer duration of the use of ART (aOR = 0.98; 95%CI 0.97-0.99) and an unawareness of their current CD4 levels (aOR = 0.54; 95% CI 0.30-0.99). To maximize the benefits from ART, there should be a bigger emphasis on the "positive prevention" program and more efforts are needed to target the population at risk for unprotected sex. Strategies to encourage adherence to ART and for disclosure of serostatus are also required. PMID- 26666293 TI - Structural insights into the mechanism defining substrate affinity in Arabidopsis thaliana dUTPase: the role of tryptophan 93 in ligand orientation. AB - BACKGROUND: Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) hydrolyzes dUTP to dUMP and pyrophosphate to maintain the cellular thymine-uracil ratio. dUTPase is also a target for cancer chemotherapy. However, the mechanism defining its substrate affinity remains unclear. Sequence comparisons of various dUTPases revealed that Arabidopsis thaliana dUTPase has a unique tryptophan at position 93, which potentially contributes to its degree of substrate affinity. To better understand the roles of tryptophan 93, A. thaliana dUTPase was studied. RESULTS: Enzyme assays showed that A. thaliana dUTPase belongs to a high-affinity group of isozymes, which also includes the enzymes from Escherichia coli and Mycobacterium tuberculosis. Enzymes from Homo sapiens and Saccharomyces cerevisiae are grouped as low-affinity dUTPases. The structure of the homo-trimeric A. thaliana dUTPase showed three active sites, each with a different set of ligand interactions between the amino acids and water molecules. On an alpha-helix, tryptophan 93 appears to keep serine 89 in place via a water molecule and to specifically direct the ligand. Upon being oriented in the active site, the C-terminal residues close the active site to promote the reaction. CONCLUSIONS: In the high affinity group, the prefixed direction of the serine residues was oriented by a positively charged residue located four amino acids away, while low-affinity enzymes possess small hydrophobic residues at the corresponding sites. PMID- 26666294 TI - Burden of mental illness on hospital and patient outcomes among asthma hospitalizations. AB - OBJECTIVE: Empirical evidence demonstrates the comorbidity of asthma and mental illness, though limited studies have evaluated the patient and hospital outcomes associated with such conditions. As such, this study evaluated the burden of this comorbidity on health resource utilization and patient disposition among asthma hospitalizations. METHODS: A secondary analysis of the Nationwide Inpatient Sample (2009-2011) was conducted, with study population of asthma hospitalizations limited to those 18 years of age and older. International Classification of Disease, 9th Revision, Clinical Modification codes were utilized to identify asthma and mental illness discharges. Length of stay was defined as number of days stayed in the hospital, total charges were inflation adjusted, and patient disposition was defined as routine versus not routine. All analyses were survey-weighted and adjusted for patient and hospital characteristics. RESULTS: Approximately 29% of the asthma hospitalizations reported mental illness. Any mental illness was associated with increased length of stay in the hospital (10% increase), total costs (11% increase), and lower odds of routine disposition (21% decrease). Substance-related disorder also increased length of stay in the hospital (4% increase), costs (9% increase), and lower odds of routine disposition (29% decrease). Age-stratified analyses further demonstrated similar trends among most age groups. CONCLUSION: The results of this study complement the extant literature by demonstrating the burden of the asthma-mental health nexus on health resource utilization and patient outcomes. The increased length of stay, cost, and decreased likelihood of routine disposition associated with mental illness highlight the need for integrated care to address mental illness as part of routine care. PMID- 26666295 TI - Shared Decision Making in mental health care using Routine Outcome Monitoring as a source of information: a cluster randomised controlled trial. AB - BACKGROUND: Shared Decision Making (SDM) is a way to empower patients when decisions are made about treatment. In order to be effective agents in this process, patients need access to information of good quality. Routine Outcome Monitoring (ROM) may provide such information and therefore may be a key element in SDM. This trial tests the effectiveness of SDM using ROM, primarily aiming to diminish decisional conflict of the patient while making decisions about treatment. The degree of decisional conflict, the primary outcome of this study, encompasses personal certainty about choosing an appropriate treatment, information about options, clarification of patient values, support from others and patients experience of an effective decision making process. Secondary outcomes of the study focus on the working alliance between patient and clinician, adherence to treatment, and clinical outcome and quality of life. METHODS/DESIGN: This article presents the study protocol of a multi-centre two arm cluster randomised controlled trial (RCT). The research is conducted in Dutch specialised mental health care teams participating in the ROM Quality Improvement Collaborative (QIC), which aims to implement ROM in daily clinical practice. In the intervention teams, ROM is used as a source of information during the SDM process between the patient and clinician. Control teams receive no specific SDM or ROM instructions and apply decision making as usual. Randomisation is conducted at the level of the participating teams within the mental health organisations. A total of 12 teams from 4 organisations and 364 patients participate in the study. Prior to data collection, the intervention teams are trained to use ROM during the SDM process. Data collection will be at baseline, and at 3 and 6 months after inclusion of the patient. Control teams will implement the SDM and ROM model after completion of the study. DISCUSSION: This study will provide useful information about the effectiveness of ROM within a SDM framework. Furthermore, with practical guidelines this study may contribute to the implementation of SDM using ROM in mental health care. Reporting of the results is expected from December 2016 onwards. TRIAL REGISTRATION: Dutch trial register: TC5262. Trial registration date: 24th of June 2015. PMID- 26666297 TI - Periocular Tissue Concentrations of Propranolol after Ocular Instillation of a Gel-Forming Solution. AB - BACKGROUND: The aim of this study was to determine the concentrations of propranolol in periocular tissues and plasma after ocular instillation of 0.5% propranolol gel-forming solution (GFS) as compared to 0.5% propranolol non gelforming solution (non-GFS) for potential use in the treatment of periocular capillary hemangiomas. METHODS: A GFS prepared in 1% sodium alginate or a non-GFS in phosphatebuffered saline was instilled into the eyes of rabbits. At predetermined time intervals after dosing, blood was withdrawn, rabbits were euthanized, and periocular tissues were dissected. RESULTS: Ocular instillation of the GFS resulted in higher concentrations of propranolol in the outer layers of both the upper and lower eyelids (in the range of 9.9-36.9 MUg/g) and maintained higher levels of propranolol in these tissues for 24 h after dosing, as compared to the ocular instillation of the non-GFS (in the range of 3.4-15.1 MUg/g). While the concentrations of propranolol in the other periocular tissues were generally similar for GFS and non-GFS at 1 h after dosing, the concentrations of propranolol in the extraocular muscles and periocular fat were higher for GFS than those for non-GFS between 4-24 h after dosing. Lower level of propranolol in plasma was observed at 1 h with GFS as compared with non-GFS. CONCLUSION: The use of the propranolol gel-forming solution can prolong drug retention on the ocular surface and increase its distribution to the outer layers of the eyelids while decreasing systemic exposure to the drug. PMID- 26666296 TI - A novel RING finger in the C-terminal domain of the coatomer protein alpha-COP. AB - The C-terminal domain of alpha-COP, an essential subunit of the COPI coatomer complex, is composed of an all alpha-helical region and a small beta-sheet domain. We show that this beta-sheet domain is a Really Interesting New Gene (RING)-like treble clef zinc finger. The zinc-binding residues are substituted by other aminoacids in many homologs including the structurally-characterized proteins from Saccharomyces cerevisiae and Bos taurus. This RING-like domain is possibly related to those of other vesicle membrane-associated complexes, such as CORVET, HOPS and SEA, and likely mediates interactions with Dsl1p and assist in coat oligomerization. PMID- 26666298 TI - Quinones and coumarins from Ajania salicifolia and their radical scavenging and cytotoxic activity. AB - 1,4-Naphthoquinone (1) and a new coumarin (3) were isolated from Ajania salicifolia, together with two known compounds (2, 4). The structures and stereochemistry of new compounds were elucidated using spectroscopic methods. Two compounds exhibited potent ABTS cation radical scavenging activities with IC50 values ranging 7.97-8.44 MUM. Two quinones (1, 2) exhibited moderate cytotoxic activity against the human cancer cell lines (Hela, HepG2, and K562) with IC50 values of 11.24-35.15 MUM in vitro. This is the first report of naphthoquinone in the genus Ajania. PMID- 26666299 TI - Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma. AB - Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break through, but levels differences in chemotherapy. Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential. PMID- 26666300 TI - A convenient "inconvenience": The eponymous legacy of Sir William Richard Gowers (1845-1915). AB - A century since his passing, the legacy of the great Victorian clinical neurologist, Sir William Richard Gowers (1845-1915), remains traceable to students and practitioners of medicine worldwide through eponymous medical terms named in his honor. Popular designations like "Gowers' sign" continue to lead curious minds to learn more about the pioneering neurologist's lifework and influence, and yet Gowers himself was not fond of medical eponyms. Memorably remarking that eponyms were an educational "inconvenience" in medicine, Gowers was apt to disfavor the system in the very same lecture in which he reportedly first referred to the spinal cord fasciculus that later took his name. This article will examine Gowers' own use of eponyms alongside the eponymous medical terms named for him, and, in the process, will show how Gowers' "inconvenience" may be of great service to the historically inclined modern clinician today. PMID- 26666302 TI - Framework of behavioral indicators evaluating TB health promotion outcomes: a modified Delphi study of TB policymakers and health workers. AB - BACKGROUND: Although TB health promotion directed at policy makers and healthcare workers (HCWs) is considered important to tuberculosis (TB) control, no indicators currently assess the impact of such promotional activities. This article is the second in a series of papers that seek to establish a framework of behavioral indicators for outcome evaluation of TB health promotion, using the Delphi method. In the first article, we sought to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. The objective of this second article is to present an indicator framework that can be used to assess behavioral outcomes of TB health promotion directed at policy makers and HCWs. METHODS: A two-round, modified Delphi method was used to establish the indicators. Sixteen experts who were knowledgeable and experienced in the field of TB control were consulted in Delphi surveys. A questionnaire was developed following 4 steps, and involved ranking indicators on a five-point Likert scale. The consensus level was 70 %. Median, mode, and Coefficient of variation (CV) were used to describe expert responses. An authority coefficient (Cr) was used to assess the degree of each expert's authority. RESULTS: Consensus was achieved following the two survey rounds and several iterations among the experts. For TB health-promotion activities directed at policymakers, the experts reached consensus on 2 domains ("Resource inputs" and "Policymaking and monitoring behaviors"), 4 subdomains ("Human resources" among others), and 13 indicators ("Human resources per 100,000 person" among others). For TB health-promotion activities directed at HCWs, the experts reached consensus on 5 domains ("Self-protective behaviors" among others), 6 sub-domains ("Preventing infection" among others), and 15 indicators ("Average hours of daily workplace disinfection by ultraviolet radiation" among others). CONCLUSIONS: This study identified a conceptual framework of core behavioral indicators to evaluate TB health-promotion activities directed at policymakers and HCWs involved in TB control. Validation in other parts of the world could lead to global consensus on behavioral indicators to evaluate TB health promotion targeted at policymakers and HCWs. PMID- 26666301 TI - The systematic early integration of palliative care into multidisciplinary oncology care in the hospital setting (IPAC), a randomized controlled trial: the study protocol. AB - BACKGROUND: Previous studies in the US and Canada, have shown the positive impact of early palliative care programs for advanced cancer patients on quality of life (QoL) and even survival time. There has been a lack of similar research in Europe. In order to generalize the findings from the US and Canada research on a larger scale, similar studies are needed in different countries with different care settings. The aim of this paper is to describe the research protocol of a randomized controlled trial, situated in Flanders, Belgium, evaluating the effect of systematic early integration of palliative care in standard oncology care. METHODS/DESIGN: A randomized controlled trial will be conducted as follows: 182 patients with advanced cancer will be recruited from the departments of Medical Oncology, Digestive Oncology and Thoracic Oncology of the Ghent University Hospital. The trial will randomize patients to either systematic early integration of palliative care in standard oncology care or standard oncology care alone. Patients and informal caregivers will be asked to fill out questionnaires on QoL, mood, illness understanding and satisfaction with care at baseline, 12 weeks and every six weeks thereafter. Other outcome measures are end of-life care decisions and overall survival time. DISCUSSION: This trial will be the first randomized controlled trial in the Belgian health care setting to evaluate the effect of systematic early integration of palliative care for advanced cancer patients. The results will enable us to evaluate whether systematic early integration of palliative care has positive effects on QoL, mood and patient illness-understanding and which components of the intervention contribute to these effects. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01865396 , registered 24(th) of May, 2013. PMID- 26666303 TI - Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study. AB - BACKGROUND: Lipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime(r)) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis. METHODS: The study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18-36 (mean age 23 +/- 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation. RESULTS: Plasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, gamma-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged. CONCLUSION: Krill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found. PMID- 26666304 TI - Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals. AB - Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID- 26666306 TI - Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor. AB - This study focuses on the structure and function of the primary sensory neurons that innervate vibrissal follicles in the rat. Both the peripheral and central terminations, as well as their firing properties were identified using intracellular labelling and recording in trigeminal ganglia in vivo. Fifty-one labelled neurons terminating peripherally, as club-like, Merkel, lanceolate, reticular or spiny endings were identified by their morphology. All neurons responded robustly to air puff stimulation applied to the vibrissal skin. Neurons with club-like endings responded with the highest firing rates; their peripheral processes rarely branched between the cell body and their terminal tips. The central branches of these neurons displayed abundant collaterals terminating within all trigeminal nuclei. Analyses of three-dimensional reconstructions reveal a palisade arrangement of club-like endings bound to the ringwulst by collagen fibers. Our morphological findings suggest that neurons with club-like endings sense mechanical aspects related to the movement of the ringwulst and convey this information to all trigeminal nuclei in the brainstem. PMID- 26666307 TI - Capturing Plant Metabolome with Direct-Immersion in Vivo Solid Phase Microextraction of Plant Tissues. AB - For the first time, an in vivo sampling mode of direct immersion-solid phase microextraction (DI-SPME) was employed to capture the metabolome of living plant specimens, using apple (Malus * domestica Borkh.) as a model system. Metabolites were extracted from apple tissues and introduced by thermal desorption into a comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry instrument. The feasibility of this sampling approach, based on exploitation of microextraction principles, including negligible depletion of free analyte concentrations, solventless sampling and sample preparation, and on-site compatibility, was determined in global metabolite analysis. Rather than adopting an approach of traditional sample preparation, requiring metabolism quenching and laborious sample preparation, the objective of the study was to capture the metabolome in vivo, evaluate the feasibility of the approach to provide unbiased extraction coverage, and compare analytical precision when different SPME sampling modes are employed. The potential of in vivo DI-SPME in quantitative plant metabolomics was assessed by evaluating changes in metabolic fingerprints in response to fruit maturation. The in vivo SPME sampling approach has been demonstrated as capable of sampling living systems with high reproducibility, considering that nearly 50% of hundreds of evaluated compounds included in the determination of analytical performance met the 15% RSD FDA criterion. Esters were extracted with high repeatability (% RSD for hexyl butanoate and butyl butanoate of 16.5 and 5.9, respectively, from 9 determinations in 3 apples) and found to be upregulated in response to apple fruit maturation. PMID- 26666305 TI - Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes. AB - Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85-1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these. PMID- 26666308 TI - Relationship between the expression of versican and EGFR, HER-2, HER-3 and CD44 in matrix-producing tumours in the canine mammary gland. AB - Versican is an extracellular matrix proteoglycan that has been identified as a modulator of adhesion loss, cell motility, and tumour progression. This motility results from the interaction between versican and cell surface receptors. Studies have also demonstrated the relationship between this molecule and invasion in canine mammary tumours. Given the evidence for the participation of proteoglycans in tumour progression, this study aimed to assess versican expression and its association with cell surface receptors; human epidermal growth factor receptors 1, 2, and 3 (EGFR, HER-2, and HER-3) and CD44 through an immunohistochemical analysis of benign mixed tumours (BMTs), carcinomas in mixed tumours (CMTs), and carcinosarcomas (CSs) of the canine mammary gland. Malignant tumours were divided into low and high groups with respect to versican stromal expression. The results indicated that the BMTs showed weak stromal versican expression and correlations between the expression of stromal versican and EGFR in the epithelial membrane in benign areas (p=0.013, r=0.571). A higher stromal versican expression was observed adjacent to invasive epithelial areas compared with in situ areas in CMTs and CSs, suggesting a direct relationship between versican expression and invasiveness. Furthermore, the CSs exhibited a higher expression of HER-2, cytoplasmic HER-3, and CD44 in epithelial invasive cells in cases of higher stromal versican expression. Therefore, the cell surface receptors (HER-2, HER-3, and CD44) are more evident in CSs that overexpress versican in stroma adjacent to the invasive areas. These findings suggest that the association between these molecules may be directly related to the biological behaviour and invasiveness of these canine mammary tumours. PMID- 26666310 TI - Acceptance of interventions to promote primary care: What do physicians prioritize? AB - BACKGROUND: Switzerland is facing a shortage of primary care physicians (PCPs); government organizations therefore suggested a broad variety of interventions to promote primary care. The aim of the study was to prioritize these interventions according to the acceptance and perceived barriers of most relevant groups of physicians in this context (hospital physicians and PCPs). METHODS: The study was conducted during summer 2014. An online-based questionnaire assessed demographic data, working conditions and future plans. Participants were asked to rank the usefulness of 22 interventions to promote primary care. Interventions to promote primary care that received ratings of 4 or 5 on the Likert scale (corresponding to "useful" or "very useful") by at least 80 % of the participants were categorized as interventions with very high acceptance. We analyzed whether the groups (PCPs, hospital physicians) ranked the interventions differently using the Mann-Whitney U test. We assumed a two tailed p < 0.05 after Bonferroni correction for multiple testing as statistically significant. RESULTS: Two hundred thirty physicians (response rate 58.4 %) completed the survey. Among those 69 PCPs and 66 hospital physicians were included in the analysis. Among those 14 PCPs were planning to leave clinical practice due to retirement, whereas only 8 hospital physicians planned a career as PCPs. Among PCPs the intervention with the highest acceptance was the increase of reimbursement, whereas family friendly measures achieved highest acceptance among hospital physicians. Financial support for primary care traineeships was considered to be very useful by both groups. CONCLUSIONS: Interventions on PCPs close to retirement or on PCPs considering an early retirement will not adequately prevent shortage of primary care providers. Governmental interventions should therefore also aim at encouraging hospital physicians to start a career in primary care by governmental support for traineeships in primary care and investments in family friendly measures. PMID- 26666311 TI - Ultradry Carbon Dioxide-in-Water Foams with Viscoelastic Aqueous Phases. AB - For foams with ultra low water contents, the capillary pressure is very large and induces rapid drainage that destabilizes the aqueous lamellae between the gas bubbles. However, we show that high-pressure CO2-in-water foams can be stabilized with a viscoelastic aqueous phase composed of entangled wormlike micelles, even for extremely high CO2 volume fractions phi of 0.95 to 0.98; the viscosity of these ultradry foams increased by up to 3-4-fold, reaching more than 100 cP relative to foams formed with conventional low viscosity aqueous phases. The foam morphology consisted of fine ~20 MUm polyhedral-shaped CO2 bubbles that were stable for hours. The wormlike micelles were formed by mixing anionic sodium lauryl ether sulfate (SLES) with salt and a protonated cationic surfactant, as shown by cryogenic transmission electron microscopy (cryo-TEM) and large values of the zero-shear viscosity and the dynamic storage and loss moduli. With the highly viscous continuous aqueous phases, the foam lamella drainage rates were low, as corroborated by confocal microscopy. The preservation of viscous thick lamellae resulted in lower rates of Ostwald ripening relative to conventional foams as shown by high-pressure optical microscopy. The ability to stabilize viscous ultra high internal phase foams is expected to find utility in various practical applications, including nearly "waterless" fracturing fluids for recovery of oil and gas in shale, offering the possibility of a massive reduction in the amount of wastewater. PMID- 26666314 TI - Template-free synthesis of porous graphitic carbon nitride/carbon composite spheres for electrocatalytic oxygen reduction reaction. AB - Porous graphitic carbon nitride/carbon composite spheres were synthesized using melamine and cyanuric acid, and glucose as the carbon nitride and carbon precursor, respectively. The 3D hierarchical composites efficiently catalyzed the oxygen reduction reaction with an onset potential of 0.90 V and a kinetic current density of 23.92 mA cm(-2). These merit their promising applications in fuel cells and metal-air batteries. PMID- 26666313 TI - The role of BMI change on smoking abstinence in a sample of HIV-infected smokers. AB - The prevalence of cigarette smoking among persons living with HIV/AIDS (PLWHA) is approximately 40%, significantly higher than that of the general population. Identifying predictors of successful smoking cessation for PLWHA is necessary to alleviate the morbidity and mortality associated with smoking in this population. Weight gain has been associated with smoking relapse in the general population, but has not been studied among PLWHA. Data from 474 PLWHA enrolled in a smoking cessation randomized clinical trial were analyzed to examine the effect of BMI change, from baseline to 3-month follow-up, on smoking outcomes using multiple logistic regression. The odds of 7-day smoking abstinence at 3-month follow-up were 4.22 (95% CI = 1.65, 10.82) times higher for participants classified as BMI decrease and 4.22 (95% CI = 1.62, 11.01) times higher for participants classified as BMI increase as compared to participants with a minimal increase or decrease in BMI. In this sample, both weight gain and loss following smoking cessation were significantly associated with abstinence at 3-month follow-up among HIV infected smokers. Further research and a better understanding of predictors of abstinence will encourage more tailored interventions, with the potential to reduce morbidity and mortality. PMID- 26666315 TI - Synthesis of 1,4-dihydrophosphinoline 1-oxides by acid-promoted cyclization of 1 (diphenylphosphoryl)allenes. AB - 1-(Diphenylphosphoryl)alka-1,2-dienes (phosphonoallenes) in Bronsted (super)acids (TfOH, FSO3H, H2SO4) gave the corresponding 1,2-oxaphosphol-3-enium ions, that were studied by means of NMR and DFT calculations. Upon hydrolysis of reaction solution, these cations afforded 3-hydroxyalk-2-en-1-yl-diphenylphosphine oxides (phosphonoallyl alcohols). But in (super)acids the cations were slowly transformed into O-protonated forms of 1-phenyl-1,4-dihydrophosphinoline 1 oxides, which were monitored by NMR. The latter phosphaheterocycles can be directly obtained from phosphonoallenes under the action of Lewis acid AlCl3. PMID- 26666316 TI - Bimetallic nickel complexes for selective CO2 carbon capture and sequestration. AB - Herein we report a dinickel azacryptand complex that enables fast, selective, and tight CO2 binding from air. Exploiting the affinity of the cavitand towards azides, CO2 release was observed. Despite the stability of the azido complex, UV irradiation under atmospheric conditions proved to be a suitable pathway for N3( ) replacement by CO2. PMID- 26666317 TI - De novo transcriptome sequence and identification of major bast-related genes involved in cellulose biosynthesis in jute (Corchorus capsularis L.). AB - BACKGROUND: Jute fiber, extracted from stem bast, is called golden fiber. It is essential for fiber improvement to discover the genes associated with jute development at the vegetative growth stage. However, only 858 EST sequences of jute were deposited in the GenBank database. Obviously, the public available data is far from sufficient to understand the molecular mechanism of the fiber biosynthesis. It is imperative to conduct transcriptomic sequence for jute, which can be used for the discovery of a number of new genes, especially genes involved in cellulose biosynthesis. RESULTS: A total of 79,754,600 clean reads (7.98 Gb) were generated using Illumina paired-end sequencing. De novo assembly yielded 48,914 unigenes with an average length of 903 bp. By sequence similarity searching for known proteins, 27,962 (57.16 %) unigenes were annotated for their function. Out of these annotated unigenes, 21,856 and 11,190 unigenes were assigned to gene ontology (GO) and euKaryotic Ortholog Groups (KOG), respectively. Searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) indicated that 14,216 unigenes were mapped to 268 KEGG pathways. Moreover, 5 Susy, 3 UGPase, 9 CesA, 18 CSL, 2 Kor (Korrigan), and 12 Cobra unigenes involving in cellulose biosynthesis were identified. Among these unigenes, the unigenes of comp11264_c0 (SuSy), comp24568_c0 (UGPase), comp11363_c0 (CesA), comp11363_c1 (CesA), comp24217_c0 (CesA), and comp23531_c0 (CesA), displayed relatively high expression level in stem bast using FPKM and RT qPCR, indicating that they may have potential value of dissecting mechanism on cellulose biosynthesis in jute. In addition, a total of 12,518 putative gene associate SNPs were called from these assembled uingenes. CONCLUSION: We characterized the transcriptome of jute, discovered a broad survey of unigenes associated with vegetative growth and development, developed large-scale SNPs, and analyzed the expression patterns of genes involved in cellulose biosynthesis for bast fiber. All these provides a valuable genomics resource, which will accelerate the understanding of the mechanism of fiber development in jute. PMID- 26666319 TI - The safety and efficacy of prednisolone in preventing reaccumulation of ascites among endomyocardial fibrosis patients in Uganda: a randomized clinical trial. AB - BACKGROUND: Endomyocardial fibrosis (EMF), the commonest restrictive cardiomyopathy worldwide, is characterized by inflammation and fibrosis of the endocardium. Inflammation in other parts of the body such as the peritoneum has been described and may explain the accumulation of ascites, a painful and disabling feature of this disease. We determined the efficacy and safety of prednisolone to prevent re-accumulation of ascites among EMF patients attending Mulago hospital cardiology service. METHODS: This was a pilot randomised placebo controlled trial with a 1:1 parallel design. Over a period of 10 months, participants were recruited and randomized to receive 1 mg/kg per day of prednisolone or placebo and were followed for a maximum of 8 weeks. The primary outcome was re-accumulation of ascites from baseline (grade 2) to grade 3. Safety was assessed by self-reported side effects, physical exam, and laboratory assessment. RESULTS: Sixteen study participants were randomised to prednisolone, while nineteen were randomised to placebo. Six were lost to follow up (1 prednisolone arm, 5-placebo). Baseline characteristics were similar between groups. Prednisolone was safely administered in this setting. There was no statistically significant difference in the overall risk of developing grade 3 ascites over 8 weeks. RR (95 % confidence interval) 0.70 (0.43-1.11), P value 0.12. The rate of the primary outcome per 1000 person days of follow-up was also similar in both arms P value 0.63. CONCLUSION: Short term prednisolone use was generally safe and did not prevent reaccumulation of ascites in this study population. TRIAL REGISTRATION NUMBER: ISRCTN63999319, 28/03/2013. PMID- 26666320 TI - Smoking and body weight: evidence from China health and nutrition survey. AB - BACKGROUND: The effects of cigarette smoking on body weight remain inconclusive. This study evaluated this relationship using the latest data from China, the largest consumer market of tobacco in the world, which is also experiencing a steady increase in patients with obesity. METHODS: Using data obtained from China Health and Nutrition Survey (CHNS) 1991-2011, Logit Model and Two-Stage Residual Inclusion (2SRI) estimation were applied. Local tobacco yield was considered as instrument variable for smoking behavior and corrected for endogeneity. RESULTS: Smoking increased the likelihood of being underweight by 0.9 % and healthy weight by 5.3 %, while the likelihood of overweight and obesity decreased by 6.5 %, of which obesity reduced by 5.1 %. After correcting for endogeneity, the results were consistent and stronger. Cigarette smoking increased the likelihood of being underweight by 2.7 % and healthy weight by 12.7 %, while it decreased the likelihood of overweight and obesity by 13 %, of which obesity reduced by 10 %. CONCLUSION: Smoking induced heterogeneous effects on body weight. Smoking had a positive effect on underweight and healthy weight, while a negative effect on overweight and obesity. Tobacco control interventions may lead to weight loss among healthy subjects, while the effects on obese subjects were not obvious as expected. PMID- 26666318 TI - The role of HCV proteins on treatment outcomes. AB - For many years, the standard of treatment for hepatitis C virus (HCV) infection was a combination of pegylated interferon alpha (Peg-IFN-alpha) and ribavirin for 24-48 weeks. This treatment regimen results in a sustained virologic response (SVR) rate in about 50% of cases. The failure of IFN-alpha-based therapy to eliminate HCV is a result of multiple factors including a suboptimal treatment regimen, severity of HCV-related diseases, host factors and viral factors. In recent years, advances in HCV cell culture have contributed to a better understanding of the viral life cycle, which has led to the development of a number of direct-acting antiviral agents (DAAs) that target specific key components of viral replication, such as HCV NS3/4A, HCV NS5A, and HCV NS5B proteins. To date, several new drugs have been approved for the treatment of HCV infection. Application of DAAs with IFN-based or IFN-free regimens has increased the SVR rate up to >90% and has allowed treatment duration to be shortened to 12 24 weeks. The impact of HCV proteins in response to IFN-based and IFN-free therapies has been described in many reports. This review summarizes and updates knowledge on molecular mechanisms of HCV proteins involved in anti-IFN activity as well as examining amino acid variations and mutations in several regions of HCV proteins associated with the response to IFN-based therapy and pattern of resistance associated amino acid variants (RAV) to antiviral agents. PMID- 26666322 TI - Novel Oral Anticoagulation--A Milestone in Anticoagulation History. PMID- 26666323 TI - Rationale for Development of New Oral Anticoagulants. AB - The development of new or direct oral anticoagulants was triggered by the disadvantages of classic oral anticoagulation, which was isolated in Link's laboratory in 1940. Some of these limitations are the individual variation in response to these drugs, drug interaction and the need for regular laboratory monitoring. With increasing comorbidity and life expectancy in populations these limitations led to interruption of treatment or even underuse of treatment in light of potential side effects. With the introduction of novel oral anticoagulants some of these drawbacks are targeted whereas even these drugs also have some limitations and should be given with cautions and not to all patients having an indication for anticoagulation. PMID- 26666321 TI - The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial. AB - BACKGROUND: Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. METHODS/DESIGN: The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. DISCUSSION: The LIPPSMAck POP trial is a multi centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013. PMID- 26666324 TI - Use of New Oral Anticoagulants in the Treatment of Venous Thromboembolism and Thrombotic Prophylaxis. AB - Thrombo-embolism of the venous system consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE) is common and associated with high morbidity and mortality. Symptomatic venous thromboembolism (VTE) manifests in about 1/3 of cases as PE and 2/3 as DVT. There is a strongly compound between early mortality after venous VTE and PE, age, malignancies and cardiovascular diseases. Anticoagulation therapy is the main therapeutic approach for the treatment of acute VTE and to prevent recurrent VTE events. For decade's classic anticoagulants like heparin, low-molecular-weight heparins (LMWHs), fondaparinux, and vitamin K antagonists have been the gold standards in therapy and are widely used. Novel oral anticoagulants (NOAC) like the direct thrombin inhibitor (dabigatran etexilate) and the direct factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) have been introduced to overcome the drawbacks of vitamin K antagonists. The efficacy and safety of these NOAC have been investigated in several randomized trials. Here we want to give an overview about the NOACS in the treatment of acute and chronic VTE and their use for primary prevention of acute VTE. PMID- 26666325 TI - The Use of Novel Oral Anticoagulants in Atrial Fibrillation. AB - Atrial fibrillation is known to be associated with an increased risk of ischaemic stroke and systemic embolism. After stratification using various risk calculation scores, patients were traditionally prescribed anticoagulants in the form of Aspirin or the traditional Vitamin K Antagonists. The use of Warfarin has proven to reduce incidents of ischaemic stroke; however its use has several limitations. The necessity for strict anticoagulation monitoring so as to maintain the narrow therapeutic range as measured by the international normalized ratio (INR) between 2 and 3 is one of these. In clinical practice, patients are within the therapeutic range lesser than two-thirds of the time and furthermore, its use is associated with a significant risk of major bleeding. The advent of Novel oral Anticoagulants marks a new era in anticoagulant therapy. The use of direct thrombin inhibitors and Factor Xa inhibitors has documented a favorable bleeding profile while being similarly or more efficacious when compared to VKA. Early studies indicate a significant reduction in the composite of stroke or systemic embolism and lowering of all-cause mortality. In this review we discuss the evidence for the clinical benefit and safety of the novel anticoagulants versus warfarin among patients with atrial fibrillation and probationary guidelines towards their use. PMID- 26666326 TI - New Oral Anticoagulants in Coronary Artery Disease. AB - The implementation of therapeutic anticoagulation influences the severity and outcome of patients with coronary artery disease (CAD). This review aims to summarize the current guideline-based recommendations about the use of new oral anticoagulants (NOACs) in patients with stable CAD (SCAD), acute coronary syndromes (ACS), percutaneous coronary interventions (PCI) and in patients with concomitant atrial fibrillation (AF). The implications of the use of specific NOACs, such as the direct factor Xa inhibitors apixaban and rivaroxaban as well as the direct thrombin inhibitor dabigatran are outlined and compared to the benefits of vitamin k antagonists and antiplatelet agents such as thienopyridines in these settings. PMID- 26666327 TI - New Oral Anticoagulation after Heart Valve Replacement. AB - Antithrombotic treatment after heart valve surgery is of utmost importance depending on the type of used valve. Since in the early 1960s, oral anticoagulation with vitamin K antagonist are the gold-standard for prevention of thromboembolism at replaced heart valves. The introduction of new oral anticoagulation has dramatically changed treatment strategy in patients with atrial fibrillation and in patients with venous thromboembolism like deep vein thrombosis and pulmonary embolism. However, to date, the use of these newer drugs is contraindicated after implantation of mechanical heart valves for prevention of thromboembolism. Large trial revealed significantly higher rates of thromboembolism and bleeding events as compared to oral anticoagulation. Further studies are required to evaluate the several newer oral anticoagulations in patients with mechanical heart valve. PMID- 26666328 TI - Novel Oral Anticoagulation During Pulmonary Vein Isolation and Cardioversion. AB - Atrial fibrillation is an age-dependent disease with symptomatic and prognostic implications. Treatment options include rhythm as well as rate control. However, there is a need for anticoagulation depending on calculated individual annual risk. Treatment options include antiplatelet therapy, oral anticoagulation and the use of novel oral anticoagulation (NOACs). To date, the safety and efficacy of NOACs in atrial fibrillation is established in large mega-trials. However, there is still concern on the use of NOACs in invasive procedures such as coronary angiography, electrophysiological procedures, and general surgical procedures. This review will give an overview about current data of NAOCs in procedures for rhythm control (pulmonary vein isolation and current cardioversion). PMID- 26666329 TI - Novel Oral Anticoagulation Laboratory Monitoring, Interaction and Treatment of Complications. AB - The use of novel oral anticoagulation (NOACs) has emerged as an alternative for oral anticoagulation with vitamin-K antagonists in different clinical settings. However, despite the several advantages of these new drugs, there are also several limitations and cautious is recommended in different clinical settings in patients with a high comorbidity index. This review article will describe the current evidence of treatment monitoring, possible drug interaction, and will give an overview about treatment options in case of complications. PMID- 26666330 TI - Novel Oral Anticoagulants: Recommendations for Patient Evaluation, Treatment Initiation, Follow-up and Perioperative Management. AB - New oral anticoagulants (NOACs) are becoming available as alternatives to vitamin K antagonists (VKAs) to prevent systemic embolism in patients with non-valvular atrial fibrillation for the prevention and treatment of venous thromboembolism and pulmonary embolism. A comprehensive understanding of the basic concepts of hemostaseology, the underlying pharmacology, drug interactions and management of potential complications is essential for the selection of suitable patients to receive NOACs, for correct prescription and for optimal patient treatment. Furthermore, the use of NOACs in a perioperative setting is crucial, as it requires knowledge of time and dose of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Although no antidote exists to reverse the effects of these novel drugs, selective substitution of coagulation factors and dialysis may be necessary. Therefore, choosing the most beneficial alternative to VKAs on an individual basis can be challenging for physicians. In conclusion, the recent introduction of NOACs represents an opportunity for anticoagulative treatment regimes, while the benefits, risks and limitations should be reflected carefully. The purpose of this systematic review is to highlight features and to provide practical guidance of NOACs in comparison with VKAs that should be considered in a multifaceted decision making process to improve efficacy and safety. PMID- 26666332 TI - Pyridinium-phosphonium dications: highly electrophilic phosphorus-based Lewis acid catalysts. AB - Using commercially available 2-pyridyldiphenylphosphine (o-NC5H4)PPh2, a family of electrophilic phosphonium cations [(o-NC5H4)PFPh2](+) (2) and dications [(o MeNC5H4)PRPh2](2+) (R = F (4); Me (5)) were prepared. The Lewis acidity of these pyridinium-phosphonium dications was probed in Friedel-Crafts dimerization, hydrodefluorination, hydrosilylation, dehydrocoupling and hydrodeoxygenation reactions. The influence of the counterion on the catalytic activity of the electrophilic phosphonium cations is also discussed. PMID- 26666331 TI - Use of peers, community lay persons and Village Health Team (VHT) members improves six-week postnatal clinic (PNC) follow-up and Early Infant HIV Diagnosis (EID) in urban and rural health units in Uganda: A one-year implementation study. AB - BACKGROUND: Effective Prevention of Mother to child Transmission of HIV (PMTCT) relies heavily on follow-up of HIV-infected women and infants from antenatal, through postnatal, to the end of the breastfeeding period. In Uganda, postnatal (PNC) follow-up remains below 50 % creating a missed opportunity for linkage to comprehensive HIV care and early infant diagnosis (EID). We evaluated the use of HIV infected peer mothers (peers), community lay persons and Village health team (VHT) members to improve PNC follow up and EID in urban and rural health units. METHODS: Study participants were HIV-infected women recruited from antenatal clinics at three urban clinics (Mulago, Rubaga and Mengo hospitals) and one rural health centre (Mpigi Health centre IV) between January and September 2010. The women were followed through delivery and the mother-infant pairs for the 6-week postnatal visit and up to 14 weeks for EID. Peers, community lay persons and VHT members were identified and trained in basic PMTCT and reproductive health (RH). They were then assigned to study clinic to support and follow study participants, their partners and infants through provision of health education, counseling, home visits, and phone call reminders. Six week PNC attendance was measured as a proportion of mother-infant pairs that returned for the 6-week postnatal follow up visit (5-8 weeks) while EID was measured as the proportion of HIV-exposed live birth that had an HIV test done by 14 weeks of age. Data at baseline (one year before the intervention) was compared with that during the one year study period among study participants and HIV infected women and their HIV-exposed infants in the whole clinic population. RESULTS: A total of 558 HIV-infected pregnant women were recruited for the study, 47 mother-infant pairs were censured before 6 weeks due to stillbirth (14), infant death < 6 weeks (23), death of participant (04) and loss to follow up before delivery (6). 401/511 (78.5 %) of mother-infant pairs returned to the study clinics at six-week, while 441/511 (86.3 %) infants were tested for HIV infection by 14 weeks of age. The baseline six-week PNC follow up was 37.7 % and increased during the study period to 78.5 % and 39.1 % among study participants and whole clinic population respectively, an incremental difference of 39.4 % (P < 0.001). EID increased from a baseline of 53.6 % to 86.3 % and 65.8 % among study and whole clinic population respectively during the study period, an incremental difference of 20.5 % (P < 0.001). CONCLUSIONS: Use of peers, community lay persons and VHT members led to a significant increase in six-week postnatal follow up of HIV infected women and EID among HIV exposed infants in the four study clinics. Our study supports the use of peers to improve early postnatal follow up and EID and should be implemented in other health units to support the PMTCT cascade. PMID- 26666333 TI - Effects of poor asthma control, insomnia, anxiety and depression on quality of life in young asthmatics. AB - OBJECTIVE: Asthma-related quality of life has previously been shown to be associated with asthma control. The aims of the present study were to further analyze this correlation, identify other variables with impact on asthma-related quality of life and investigate the covariance among these variables. METHODS: Information was retrieved from a cohort of 369 patients, aged 12-35, with physician-diagnosed asthma requiring anti-inflammatory treatment for at least 3 months per year. Questionnaire data [including the mini-Asthma Quality of Life Questionnaire (mAQLQ), asthma control test (ACT) and Hospital Anxiety and Depression Scale (HADS)], quality of sleep, lung function data and blood samples were analyzed. Linear regression models with the mAQLQ score as the dependent scalar variable were calculated. RESULTS: ACT was the single variable that had the highest explanatory value for the mAQLQ score (51.5%). High explanatory power was also observed for anxiety and depression (17.0%) and insomnia (14.1%). The population was divided into groups depending on the presence of anxiety and depression, uncontrolled asthma and insomnia. The group that reported none of these conditions had the highest mean mAQLQ score (6.3 units), whereas the group reporting all of these conditions had the lowest mAQLQ score (3.8 units). CONCLUSIONS: The ACT score was the single most important variable in predicting asthma-related quality of life. Combining the ACT score with the data on insomnia, anxiety and depression showed considerable additive effects of the conditions. Hence, we recommend the routine use of the ACT and careful attention to symptoms of insomnia, anxiety or depression in the clinical evaluation of asthma-related quality of life. PMID- 26666334 TI - The moderating role of personality traits in the relationship between work and salivary cortisol: a cross-sectional study of 401 employees in 34 Canadian companies. AB - BACKGROUND: The objective of this study was to evaluate the contribution of personality traits in explaining the relationship between workplace stressors and variations in salivary cortisol concentrations. METHOD: Multilevel regression analyses were performed on a sample of 401 employees from 34 Quebec firms. Saliva samples were collected five times a day (on awakening, 30 min after awakening, and at 2 p.m., 4 p.m., and bedtime). Sample collection was repeated on three days (1 rest day, 2 working days). Work-related variables comprised skill utilization, decision authority, psychological demands, physical demands, job insecurity, irregular schedule, number of working hours, and social support from coworkers and supervisors. Personality traits comprised self-esteem, locus of control, and the Big Five. RESULTS: Cortisol levels at awakening and 30 min later were significantly higher for work days than for days off. Psychological demands and job insecurity were associated with lower cortisol levels at bedtime. Also, self esteem moderated the relationship between physical demands and cortisol levels at awakening and 4 p.m. Agreeableness was associated with lower cortisol levels at awakening and at 2 p.m. and further moderated the relationship between number of hours worked and cortisol at 2 p.m. Neuroticism moderated the relationship between coworker support and cortisol at bedtime. CONCLUSION: Specific working conditions and certain personality traits are associated with variations in salivary cortisol concentrations. In addition, certain personality traits moderate the relationship between stressors and salivary cortisol concentrations. In conclusion, salivary cortisol concentrations at work seem to be modulated in part by personality traits. PMID- 26666337 TI - Immmunodeficiencies and autoimmune diseases: common variable immunodeficiency and Crohn-like. AB - Common variable immunodeficiency (CVI) gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60 % present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%). We present the case of a patient with CVI with digestive symptoms being diagnosed of Crohn-like disease with extent ileal affectation. The main treatment of these patients is the same as classical Crohn disease although in the most severe cases, as this one, the use of immunosupresors is necessary. At this time the patient remains on clinical remmision with infliximab. She presented a previous adverse reaction with adalimumab. The few case series in this pathology makes the treatment with immunomodulators in this immunodeficiency a real diagnostic and therapeutic challenge. PMID- 26666335 TI - Causes of changes in carotid intima-media thickness: a literature review. AB - Atherosclerosis causes significant morbidity and mortality. Carotid intima-media thickness (CIMT) predicts future cardiovascular and ischaemic stroke incidence. CIMT, a measure of atherosclerotic disease, can be reliably determined in vivo by carotid ultrasound. In this review, we determined that CIMT is associated with traditional cardiovascular risk factors such as age, sex, race, smoking, alcohol consumption, habitual endurance exercise, blood pressure, dyslipidemia, dietary patterns, risk-lowering drug therapy, glycemia, hyperuricemia, obesity-related anthropometric parameters, obesity and obesity-related diseases. We also found that CIMT is associated with novel risk factors, including heredity, certain genotypic indices, anthropometric cardiovascular parameters, rheumatoid arthritis, immunological diseases, inflammatory cytokines, lipid peroxidation, anthropometric hemocyte parameters, infectious diseases, vitamin D, matrix metalloproteinases, and other novel factors and diseases. However, the conclusions are inconsonant; the underlying causes of these associations remain to be further explored. PMID- 26666336 TI - Risk of de novo post-transplant type 2 diabetes in patients undergoing liver transplant for non-alcoholic steatohepatitis. AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is often seen together with components of metabolic syndrome. The aim of this study was to assess the risk of de novo post-transplant type 2 diabetes (DM) in liver transplant recipients with NASH. METHODS: All adult patients from the Scientific Registry of Transplant Recipients (2003-2012) transplanted for NASH or cryptogenic cirrhosis (the NASH cohort) without pre-transplant DM were included in this retrospective cross sectional study. RESULTS: Total 2,916 NASH subjects and 14,268 controls with non HCV related cirrhosis or hepatocellular carcinoma were included. Patients with NASH were, on average, 6 years older, more likely female and overweight/obese. By 5 years post-transplant, 39.8% NASH vs. 27.0% controls developed at least one onset of de novo DM; this was observed starting 6 months post-transplant: 22.9% vs. 16.7% (relative risk 1.38). Later in follow-up, the relative risk of de novo DM was also higher in NASH: 1.46 by 3 years, 1.47 by 5 years (all p < 0.0001). After exclusion of DM that resolved after the first year, long-term DM remained higher in the NASH cohort: 7.6% vs. 4.3%, p < 0.0001. In multivariate analysis, after adjustment for confounders including the use of immunosuppressants, having NASH was independently associated with development of de novo post-transplant DM: adjusted hazard ratio (95% CI) = 1.29 (1.18-1.42), p < 0.0001. CONCLUSIONS: Liver transplant recipients with NASH have a higher risk of de novo post-transplant DM. This suggests the presence of an underlying metabolic disorder beyond fatty liver that may be causative for both NASH and type 2 diabetes. PMID- 26666338 TI - Lucidimine A-D, four new alkaloids from the fruiting bodies of Ganoderma lucidum. AB - Four new polycylic alkaloids, lucidimine A-D, were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established based on 1D and 2D NMR data as well as HREIMS/HRESIMS analyses. PMID- 26666339 TI - Incidence and outcomes for adults diagnosed with acute myeloid leukemia in the north of England: a real world study. AB - We conducted a retrospective population-based study of patients diagnosed with acute myeloid leukemia (AML) in northern England (population 3.1 million) in order to assess the impact of age and genetics on outcome. Four hundred and sixteen patients were diagnosed with AML, between 2007 and 2011. In those aged <=60 years (n = 20) with acute promyelocytic leukemia (APL) overall survival (OS) was 100%. For non-APL patients aged <=60 years, OS for those with favorable, intermediate and adverse cytogenetics was not reached, 17 and 9.8 months, respectively (p = 0.0001). Of particular note, intensively treated patients aged >60 years with intermediate cytogenetics and FLT3-/NPM1+ status had a five-year survival of 60% versus median OS of 11 months for other subsets (p = 0.04). Population-based studies reduce selection bias and have utility in studying rarer diseases, particularly in populations that recruit poorly to trials. The highly favorable outcome in our subgroup of intensively-treated FLT3-/NPM1+ older patients merits further study. PMID- 26666340 TI - How do national cultures influence lay people's preferences toward doctors' style of communication? A comparison of 35 focus groups from an European cross national research. AB - BACKGROUND: The evidence that inspires and fosters communication skills, teaching programmes and clinical recommendations are often based on national studies which assume, implicitly, that patients' preferences towards doctors' communication style are not significantly affected by their cultural background. The cross cultural validity of national results has been recognized as a potential limitation on how generally applicable they are in a wider context. Using 35 country-specific focus group discussions from four European countries, the aim of the present study is to test whether or not national cultures influence lay people's preferences towards doctors' style of communication. METHODS: Lay people preferences on doctor's communication style have been collected in Belgium, the Netherlands, the United Kingdom and Italy. Each centre organized between eight and nine focus groups, where participants (n = 259) were asked to comment on a video of a simulated medical interview. The discussions were audiotaped, transcribed and coded using a common framework (Guliver Coding System) that allowed for the identification of different themes. RESULTS: The frequency distribution of the topics discussed highlights lay people's generally positive views towards most part of doctors interventions. The regression model applied to the Guliver categories highlighted slight national differences and the existence of a cross-cultural appreciation, in particular, of five types of intervention: Doctors attitudes (both Task-Oriented and Affective/Emotional), Summarizing, Structuring and Providing solution. CONCLUSION: Lay panels valued doctors' communication style in a similar manner in the countries selected. This highlights the existence of a common background, which in the process of internationalization of heath care, might foster the implementation of cross national teaching programmes and clinical guidelines. PMID- 26666341 TI - Intestinal helminth infections among inmates in Bedele prison with emphasis on soil-transmitted helminths. AB - BACKGROUND: Intestinal helminths infect more than two billion people worldwide. They are common in developing countries where sanitary facilities are inadequate. There is scarcity of documented data on the magnitude of intestinal helminths among inmates in Ethiopia. The aim of this study was to determine prevalence of intestinal helminth infections among inmates in Bedele prison, south-western Ethiopia. METHODS: A cross-sectional study involving 234 inmates in Bedele prison was conducted in April 2012. Socio-demographic data was collected from each study participant using semi-structured questionnaire. Fresh stool specimens were collected and processed using modified McMaster technique. RESULTS: At least one species of intestinal helminth was identified in 111 (47.4 %) of the inmates. Ascaris lumbricoides was the most predominant parasite isolated, followed by the hookworms. Most of the cases of soil-transmitted helminths (STHs) were light infections. Untrimmed hand fingernails was significantly associated with A. lumbricoides infection (AOR 0.383, 95 % CI 0.200-0.731). CONCLUSION: Intestinal helminths are common among the inmates in Bedele prison. Health information should be given to the inmates on proper personal hygiene practices with emphasis on trimming of hand fingernails. Monitoring helminth infections in the inmate population is required. PMID- 26666342 TI - Procalcitonin-based indication of bacterial infection identifies high risk acute heart failure patients. AB - BACKGROUND: Bacterial infections in patients hospitalized with acute heart failure are related to worse prognosis, but they can be difficult to diagnose. In this study we evaluated the prevalence, clinical correlates and association with outcomes of significantly elevated procalcitonin levels in patients hospitalized for acute heart failure without clear signs of bacterial infection. METHODS: 1781 patients from the PROTECT trial were included. Patients with a body temperature >38 degrees C, sepsis or active infection requiring IV antibiotics were excluded. Significant elevation of procalcitonin was considered present when levels exceeded 0.20 ng/mL. In-hospital and post-discharge outcomes were compared between groups of patients with and without elevated procalcitonin levels. RESULTS: Procalcitonin >= 0.20 ng/mL was seen in 6.0% of patients (N=104). This group of patients had lower serum albumin, lower hemoglobin, higher leukocyte count, higher C-reactive protein, higher blood urea nitrogen, higher heart rate and more pulmonary rales. Interestingly, no significant differences were observed between the two groups in terms of severity of heart failure evidenced by left ventricular ejection fraction (LVEF) or B-type natriuretic peptide (BNP) levels. Patients with significantly elevated procalcitonin levels were more often classified as treatment failure or unchanged status, and had an increased risk of 30-day all-cause mortality even after adjustment for established prognosticators; HR=2.3 (95% CI, 1.3-4.2), (P=0.005). CONCLUSION: Patients with acute heart failure and significantly elevated procalcitonin levels, indicating probable undiagnosed/untreated bacterial infection, had poorer in-hospital and post discharge outcomes, despite similar severity of heart failure. PMID- 26666343 TI - CD-144 positive endothelial microparticles are increased in patients with systemic inflammatory response syndrome after TAVI. PMID- 26666344 TI - Who is the culprit for the patient with acute myocardial infarction, plaque rupture or essential thrombocytosis? PMID- 26666345 TI - A heartbreaking pleasure. PMID- 26666346 TI - Longitudinal stent foreshortening of Stentys Xposition S self-apposing stents and its impact on overlapping stenting strategy. PMID- 26666347 TI - Interpreting IgE sensitization tests in food allergy. AB - Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy. PMID- 26666349 TI - Assessment of the "July Effect": outcomes after early resident transition in adult neurosurgery. AB - OBJECT Each July, 4th-year medical students become 1st-year resident physicians and have much greater responsibility in making management decisions. In addition, incumbent residents and fellows advance to their next postgraduate year and face greater challenges. It has been suggested that among patients who have resident physicians as members of their neurosurgical team, this transition may be associated with increased rates of morbidity and mortality, a phenomenon known as the "July Effect." In this study, the authors compared morbidity and mortality rates between the initial and later months of the academic year to determine whether there is truly a July Effect that has an impact on this patient population. METHODS The authors compared 30-day postoperative outcomes of neurosurgery performed by surgical teams that included resident physicians in training during the first academic quarter (Q1, July through September) with outcomes of neurosurgery performed with resident participation during the final academic quarter (Q4, April through June), using 2006-2012 data from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Regression analyses were performed on outcome data that included mortality, surgical complications, and medical complications, which were graded as mild or severe. To determine whether a July Effect was present in subgroups, secondary analyses were performed to analyze the association of outcomes with each major neurosurgical subspecialty, the postgraduate year of the operating resident, and the academic quarter during which the surgery was performed. To control for possible seasonal trends in certain diseases, the authors compared patient outcomes at academic medical centers to those at community-based hospitals, where procedures were not performed by residents. In addition, the efficiency of academic centers was compared to that of community centers in terms of operative duration and total length of hospital stay. RESULTS Overall, there were no statistically significant differences in mortality, morbidity, or efficiency between the earlier and later quarters of the academic year, a finding that also held true among neurosurgical subspecialties and among postgraduate levels of training. There was, however, a slight increase in intraoperative transfusions associated with the transitional period in July (6.41% of procedures in Q4 compared to 7.99% in Q1 of the prior calendar year; p = 0.0005), which primarily occurred in cases involving junior (2nd- to 4th-year) residents. In addition, there was an increased rate of reoperation (1.73% in Q4 to 2.19% in Q1; p < 0.0001) observed mainly among senior (5th- to 7th-year) residents in the early academic months and not paralleled in our community cohort. CONCLUSIONS There is minimal evidence for a significant July Effect in adult neurosurgery. Our results suggest that, overall, the current resident training system provides enough guidance and support during this challenging transition period. PMID- 26666348 TI - Transcriptome and proteome dynamics in larvae of the barnacle Balanus Amphitrite from the Red Sea. AB - BACKGROUND: The barnacle Balanus amphitrite is widely distributed in marine shallow and tidal waters, and has significant economic and ecological importance. Nauplii, the first larval stage of most crustaceans, are extremely abundant in the marine zooplankton. However, a lack of genome information has hindered elucidation of the molecular mechanisms of development, settlement and survival strategies in extreme marine environments. We sequenced and constructed the genome dataset for nauplii to obtain comprehensive larval genetic information. We also investigated iTRAQ-based protein expression patterns to reveal the molecular basis of nauplii development, and to gain information on larval survival strategies in the Red Sea marine environment. RESULTS: A nauplii larval transcript dataset, containing 92,117 predicted open reading frames (ORFs), was constructed and used as a reference for the proteome analysis. Genes related to translation, oxidative phosphorylation and cytoskeletal development were highly abundant. We observed remarkable plasticity in the proteome of Red Sea larvae. The proteins associated with development, stress responses and osmoregulation showed the most significant differences between the two larval populations studied. The synergistic overexpression of heat shock and osmoregulatory proteins may facilitate larval survival in intertidal habitats or in extreme environments. CONCLUSIONS: We presented, for the first time, comprehensive transcriptome and proteome datasets for Red Sea nauplii. The datasets provide a foundation for future investigations focused on the survival mechanisms of other crustaceans in extreme marine environments. PMID- 26666350 TI - Quasi-planktonic behavior of foraging top marine predators. AB - Monitoring marine top predators is fundamental for assessing the health and functioning of open ocean ecosystems. Although recently tracking observations have substantially increased, factors determining the horizontal exploration of the ocean by marine predators are still largely unknown, especially at the scale of behavioral switches (1-100 km, days-weeks). It is commonly assumed that the influence of water movement can be neglected for animals capable of swimming faster than the current. Here, we challenge this assumption by combining the use of biologging (GPS and accelerometry), satellite altimetry and in-situ oceanographic data (ADCP and drifting buoys) to investigate the effect of the mesoscale ocean dynamics on a marine predator, the southern elephant seal. A Lagrangian approach reveals that trajectories of elephant seals are characterized by quasi-planktonic bouts where the animals are horizontally drifting. These bouts correspond to periods of increased foraging effort, indicating that in the quasi-planktonic conditions energy is allocated to diving and chasing, rather than in horizontal search of favourable grounds. These results suggest that mesoscale features like eddies and fronts may act as a focal points for trophic interactions not only by bottom-up modulation of nutrient injection, but also by directly entraining horizontal displacements of the upper trophic levels. PMID- 26666352 TI - Correction: Multivalent presentation of carbohydrates by 3(14)-helical peptide templates: synthesis, conformational analysis using CD spectroscopy and saccharide recognition. AB - Correction for 'Multivalent presentation of carbohydrates by 314-helical peptide templates: synthesis, conformational analysis using CD spectroscopy and saccharide recognition' by Nitin J. Pawar et al., Org. Biomol. Chem., 2015, 13, 11278-11285. PMID- 26666351 TI - The ideal healthcare: priorities of people with chronic conditions and their carers. AB - BACKGROUND: It is well established that health consumer opinions should be considered in the design, delivery, and evaluation of health services. However, the opinions of people with chronic conditions and their carers and what they actually consider as ideal healthcare is limited. The aim of this study is to investigate the healthcare priorities of consumers with chronic conditions and their carers, if there are differences between these two groups, and if priorities differ depending on geographical location. METHODS: The nominal group technique was used as a method to identify what is currently important to, or valued by, participants. This method was also particularly suited to learning about healthcare problems and generating important solutions, thereby helping to bridge the gap between research and policy. Recruitment was carried out via purposive sampling, with the assistance of community pharmacies, general practices, various health agencies, government and non-government organisations. A total of 11 nominal groups were conducted; five groups consisted predominantly of consumers (n = 33 participants), two groups consisted predominantly of carers (n = 12 participants) and four were mixed groups, i.e. consumers, carers, and both (n = 26 participants). RESULTS: The findings suggested that to create a model of ideal healthcare for people with chronic conditions and their carers, appropriate and timely healthcare access was of paramount importance. Continuity and coordinated care, patient-centred care and affordability were equally the second most important healthcare priorities for all groups. When compared with other groups, access was discussed more frequently among participants residing in the rural area of Mount Isa. Compared to consumers, carers also discussed priorities that were more reminiscent with their caring roles, such as increased access and continuity and coordinated care. CONCLUSIONS: Access to healthcare is the most important priority for people with chronic conditions and their carers. In the event of inappropriate access for certain groups, all other efforts to increase the quality of healthcare delivery, e.g. patient-centred care, may be pointless. However, health professionals alone may be limited in their ability to address the concerns related to healthcare access; structural changes by health policy makers may be needed. PMID- 26666353 TI - ACL Reconstruction Decision Support. Personalized Simulation of the Lachman Test and Custom Activities. AB - INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". OBJECTIVES: The objective of the proposed approach is to develop a clinical decision support system (DSS) that will help clinicians optimally plan the ACL reconstruction procedure in a patient specific manner. METHODS: A full body model is developed in this study with 23 degrees of freedom and 93 muscles. The knee ligaments are modeled as non-linear spring-damper systems and a tibiofemoral contact model was utilized. The parameters of the ligaments were calibrated based on an optimization criterion. Forward dynamics were utilized during simulation for predicting the model's response to a given set of external forces, posture configuration and physiological parameters. RESULTS: The proposed model is quantified using MRI scans and measurements of the well-known Lachman test, on several patients with a torn ACL. The clinical potential of the proposed framework is demonstrated in the context of flexion-extension, gait and jump actions. The clinician is able to modify and fine tune several parameters such as the number of bundles, insertion position on the tibia or femur and the resting length that correspond to the choices of the surgical procedure and study their effect on the biomechanical behavior of the knee. CONCLUSION: Computational knee models can be used to predict the effect of surgical decisions and to give insight on how different parameters can affect the stability of the knee. Special focus has to be given in proper calibration and experimental validation. PMID- 26666355 TI - Modified box dimension and average weighted receiving time on the weighted fractal networks. AB - In this paper a family of weighted fractal networks, in which the weights of edges have been assigned to different values with certain scale, are studied. For the case of the weighted fractal networks the definition of modified box dimension is introduced, and a rigorous proof for its existence is given. Then, the modified box dimension depending on the weighted factor and the number of copies is deduced. Assuming that the walker, at each step, starting from its current node, moves uniformly to any of its nearest neighbors. The weighted time for two adjacency nodes is the weight connecting the two nodes. Then the average weighted receiving time (AWRT) is a corresponding definition. The obtained remarkable result displays that in the large network, when the weight factor is larger than the number of copies, the AWRT grows as a power law function of the network order with the exponent, being the reciprocal of modified box dimension. This result shows that the efficiency of the trapping process depends on the modified box dimension: the larger the value of modified box dimension, the more efficient the trapping process is. PMID- 26666354 TI - Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice. AB - Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose dependently fetal death during GD12.5-16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis. PMID- 26666356 TI - A rapid evidence review on the effectiveness of institutional health partnerships. AB - BACKGROUND: Institutional Health Partnerships are long-term, institution to institution partnerships between high income and low and middle income countries which seek to build capacity and strengthen health institutions in order to improve health service delivery and outcomes. Funding for Institutional Health Partnerships has increased in recent years. This paper outlines a rapid evidence review on the effectiveness of this modality. METHODS: A rapid evidence review of published and grey literature was conducted. Content relating to the effectiveness of working in partnership and methods and frameworks used were extracted and analysed. The results of this analysis were used to structure a discussion regarding the next steps to strengthen the evidence base for the effectiveness of institutional health partnerships. RESULTS: The evidence review, including citation mapping, returned 27 published papers and 17 grey literature documents that met all of the inclusion criteria. Most of the literature did not meet the high standards of formal academic rigour and there was no original research amongst this literature that specifically addressed the effectiveness of institutional health partnerships. This was not surprising given institutional health partnerships do not lend themselves easily to case control studies and randomised control trials due to their high level of diversity and operation in complex social systems. There was, however, a body of practice based knowledge and experience. CONCLUSIONS: Evidence for the effectiveness of Institutional Health Partnerships is thin both in terms of quantity and academic rigour. There is a need to better define and differentiate Institutional Health Partnerships in order to measure and compare effectiveness across such a diverse group. Effectiveness needs to be measured at the level of individual partnerships, the bodies that facilitate partnership programmes and the level of health service delivery. There is a need to develop indicators and frameworks that specifically address the benefits and values of partnership working and how these relate to effectiveness. These indicators need to be content neutral of specific interventions which are already measured through routine project monitoring and evaluation. This will allow the development of methodological pathways to assess the effectiveness of institutional health partnerships. Until more primary research is conducted or published there is little benefit in further systematic reviews. PMID- 26666357 TI - Fasting serum blood measures of bone and lipid metabolism in children with myelomeningocele for early detection of cardiovascular and bone fragility risk factors. AB - OBJECTIVE: This study examined serum levels in children with myelomeningocele to identify the prevalence of pre-clinical signs of disease. DESIGN: A prospective, cross-sectional study. SETTING: Patients were actively recruited from multidisciplinary care clinics at tertiary children's hospitals from 2010-2012. The control comparison group was recruited by word-of-mouth. PATIENTS: Twenty eight children with myelomeningocele (93% Hispanic; 17 males; 10.0 +/- 2.1 years) and 58 controls (84% Hispanic; 30 males; 10.4 +/- 2.4 years) provided >= 8-hour fasting blood samples with concomitant dual-energy x-ray absorptiometry measurements of body fat. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The serum analysis included a lipid panel (cholesterol, triglycerides, high density lipoprotein, low-density lipoprotein), insulin, glucose, leptin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, albumin, creatinine, calcium, phosphatase, parathyroid hormone, and vitamin D. RESULTS: Children with myelomeningocele had higher body fat (35.2% versus 29.9%, p=0.01) and altered lipid profiles (lower high-density lipoprotein levels, 43.9 mg/dL versus 51.6 mg/dL, P = 0.03) suggesting elevated risk of metabolic syndrome. They also had a higher prevalence of vitamin D deficiency (43% versus 17%, p=0.02) and significantly lower levels of calcium (9.4 mg/dL versus 9.7 mg/dL, P = 0.003) and alkaline phosphatase (187.0 U/L versus 237.0 U/L, P = 0.003). Unexpectedly children with myelomeningocele had lower parathyroid hormone levels (14.5 pg/mL versus 18.4 pg/mL, P = 0.02) than controls despite lower calcium, vitamin D and alkaline phosphatase levels. This suggests an alteration in the sensing mechanism or response of the parathyroid gland to normal physiological stimuli in patients with myelomeningocele. CONCLUSIONS: Children with myelomeningocele have abnormal biochemical markers for cardiovascular disease, insulin resistance and bone and mineral metabolism. Early recognition and monitoring of these risk factors in patients with myelomeningocele may help prevent later complications. PMID- 26666358 TI - Workforce development to provide person-centered care. AB - OBJECTIVES: Describe the development of a competent workforce committed to providing patient-centered care to persons with dementia and/or depression and their caregivers; to report on qualitative analyses of our workforce's case reports about their experiences; and to present lessons learned about developing and implementing a collaborative care community-based model using our new workforce that we call care coordinator assistants (CCAs). METHOD: Sixteen CCAs were recruited and trained in person-centered care, use of mobile office, electronic medical record system, community resources, and team member support. CCAs wrote case reports quarterly that were analyzed for patient-centered care themes. RESULTS: Qualitative analysis of 73 cases using NVivo software identified six patient-centered care themes: (1) patient familiarity/understanding; (2) patient interest/engagement encouraged; (3) flexibility and continuity of care; (4) caregiver support/engagement; (5) effective utilization/integration of training; and (6) teamwork. Most frequently reported themes were patient familiarity - 91.8% of case reports included reference to patient familiarity, 67.1% included references to teamwork and 61.6% of case reports included the theme flexibility/continuity of care. CCAs made a mean number of 15.7 (SD = 15.6) visits, with most visits for coordination of care services, followed by home visits and phone visits to over 1200 patients in 12 months. DISCUSSION: Person centered care can be effectively implemented by well-trained CCAs in the community. PMID- 26666359 TI - Estrone sulfate and dehydroepiandrosterone sulfate: Transactivation of the estrogen and androgen receptor. AB - Dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E1S) are two of the most abundant steroids in the human circulation. The enzyme steroid sulfatase (STS) cleaves the sulfate group of DHEAS and E1S leading to biosynthesis of endogenous hormones such as testosterone and estrone. In the current study we aimed at determining the effect of E1S and DHEAS on estrogen receptor (ER) and androgen receptor (AR) transactivation. Using luciferase reporter gene assays, the ER and AR transactivities of E1S and DHEAS were determined by direct cell exposure; as well as upon extraction from human serum using a method to extract perfluorinated alkyl acids (PFAAs). By direct cell exposure, both E1S and DHEAS transactivated the ER and the AR in dose-dependent manners. The DHEAS-induced AR transactivity could be abolished by the STS inhibitor STX64. Immunoassay analysis confirmed the presence of E1S and DHEAS in the serum PFAA extracts with mean recoveries below 2.5%. For the PFAA extracts of human male and female serum, only the AR was significantly transactivated. The AR transactivity of the sulfated steroids in the extracts was abolished by STX64 to obtain the net PFAA induced xenohormone transactivity, but further cleanup might be needed at high concentrations of E1S. PMID- 26666360 TI - Microbial transformation of danazol with Cunninghamella blakesleeana and anti cancer activity of danazol and its transformed products. AB - Biotransformation of danazol (1) (17beta-hydroxy-17alpha-pregna-2,4-dien-20-yno [2,3-d]-isoxazole) with Cunninghamella blakesleeana yielded three new metabolites 2-4 and a known metabolite 5. These metabolites were identified as 14beta,17beta dihydroxy-2-(hydroxymethyl)-17alpha-pregn-4-en-20-yn-3-one (2), 1alpha,17beta dihydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (3), 6beta,17beta dihydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (4), and 17beta hydroxy-2-(hydroxymethyl)-17alpha-pregn-1,4-dien-20-yn-3-one (5). Danazol (1) and its derivatives were evaluated against cervical cancer cell line (HeLa). Compound 1 showed a potent cytotoxicity with IC50=0.283+/-0.013 MUM, as compared to doxorubicin (IC50=0.506+/-0.015 MUM), where compound 3 was also found to be significantly active with IC50=13.427+/-0.819 MUM. PMID- 26666361 TI - Pharmacology: On the mode of action of mirabegron. PMID- 26666362 TI - Testicular cancer: PD-L1: a promising target for TGCTs. PMID- 26666364 TI - The challenging landscape of medical device approval in localized prostate cancer. AB - Findings of research using modern multiparametric MRI have provided clinicians with reliable targets for guiding prostate biopsy sampling and directing targeted therapy, often termed focal therapy, to specific areas of the prostate. This emerging shift in treatment strategy from a whole-gland approach to a lesion specific or region-specific approach requires novel medical devices. The rules regulating the approval and clinical use of such new devices often differ between the USA and Europe, and these differences can affect the treatments that patients receive. Current regulatory pathways for approval of various image-guided biopsy and focal therapy devices intended to be used in patients with prostate cancer are discussed in detail. Finally, we offer some perspective on the current status of research in the field, and propose a potential roadmap towards the establishment of timely, safe and standardized criteria for optimal evaluation of novel image-guided devices for treatment of patients with localized prostate cancer. PMID- 26666366 TI - 1,2,4-Diazaphospholide complexes of yttrium(iii), dysprosium(iii), erbium(iii), and europium(ii,iii): synthesis, X-ray structural characterization, and EPR analysis. AB - Several structurally characterized heteroleptic, charge-separated heterobimetallic, and polymeric alkali metal ate complexes of 1,2,4 diazaphospholide Y(iii), Dy(iii), Er(iii), Eu(iii), and Eu(ii) were prepared via the reaction of MCl3 and K[3,5-R2dp] in varied ratios at 200-220 degrees C (M = Y, Dy, Er, Eu; R = tBu, Ph). PMID- 26666365 TI - Prostate cancer: Cardiac mortality associated with ADT plus radiotherapy. PMID- 26666367 TI - Bridging the "green gap" of LEDs: giant light output enhancement and directional control of LEDs via embedded nano-void photonic crystals. AB - Green LEDs do not show the same level of performance as their blue and red cousins, greatly hindering the solid-state lighting development, which is the so called "green gap". In this work, nano-void photonic crystals (NVPCs) were fabricated to embed within the GaN/InGaN green LEDs by using epitaxial lateral overgrowth (ELO) and nano-sphere lithography techniques. The NVPCs act as an efficient scattering back-reflector to outcouple the guided and downward photons, which not only boost the light extraction efficiency of LEDs with an enhancement of 78% but also collimate the view angle of LEDs from 131.5 degrees to 114.0 degrees . This could be because of the highly scattering nature of NVPCs which reduce the interference giving rise to Fabry-Perot resonance. Moreover, due to the threading dislocation suppression and strain relief by the NVPCs, the internal quantum efficiency was increased by 25% and droop behavior was reduced from 37.4% to 25.9%. The enhancement of light output power can be achieved as high as 151% at a driving current of 350 mA. Giant light output enhancement and directional control via NVPCs point the way towards a promising avenue of solid state lighting. PMID- 26666363 TI - The interplay of extracellular matrix and microbiome in urothelial bladder cancer. AB - Many pathological changes in solid tumours are caused by the accumulation of genetic mutations and epigenetic molecular alterations. In addition, tumour progression is profoundly influenced by the environment surrounding the transformed cells. The interplay between tumour cells and their microenvironment has been recognized as one of the key determinants of cancer development and is being extensively investigated. Data suggest that both the extracellular matrix and the microbiota represent microenvironments that contribute to the onset and progression of tumours. Through the introduction of omics technologies and pyrosequencing analyses, a detailed investigation of these two microenvironments is now possible. In urological research, assessment of their dysregulation has become increasingly important to provide diagnostic, prognostic and predictive biomarkers for urothelial bladder cancer. Understanding the roles of the extracellular matrix and microbiota, two key components of the urothelial mucosa, in the sequelae of pathogenic events that occur in the development and progression of urothelial carcinomas will be important to overcome the shortcomings in current bladder cancer treatment strategies. PMID- 26666368 TI - Concealing Emotions at Work Is Associated with Allergic Rhinitis in Korea. AB - Concealing emotions at work can cause considerable psychological stress. While there is extensive research on the adverse health effects of concealing emotions and the association between allergic diseases and stress, research has not yet investigated whether concealing emotions at work is associated with allergic rhinitis. Allergic rhinitis is a common disease in many industrialized countries, and its prevalence is increasing. Thus, our aim was to determine the strength of this association using data from three years (2007-2009) of the 4th Korean National Health and Nutrition Examination Survey. Participants (aged 20-64) were 8,345 individuals who were economically active and who had completed the questionnaire items on concealing emotions at work. Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for allergic rhinitis using logistic regression models. Among all participants, 3,140 subjects (37.6%) reported concealing their emotions at work: 1,661 men and 1,479 women. The OR (95% CIs) for allergic rhinitis among those who concealed emotions at work versus those who did not was 1.318 (1.148-1.512). Stratified by sex, the OR (95% CIs) was 1.307 (1.078-1.585) among men and 1.346 (1.105-1.639) among women. Thus, individuals who concealed their emotions at work were significantly more likely to have a diagnosis of AR in comparison to those who did not. Because concealing emotions at work has adverse health effects, labor policies that aim to reduce this practice are needed. PMID- 26666369 TI - Sleep-related crash characteristics: Implications for applying a fatigue definition to crash reports. AB - Sleep-related (SR) crashes are an endemic problem the world over. However, police officers report difficulties in identifying sleepiness as a crash contributing factor. One approach to improving the sensitivity of SR crash identification is by applying a proxy definition post hoc to crash reports. To identify the prominent characteristics of SR crashes and highlight the influence of proxy definitions, ten years of Queensland (Australia) police reports of crashes occurring in >=100km/h speed zones were analysed. In Queensland, two approaches are routinely taken to identifying SR crashes. First, attending police officers identify crash causal factors; one possible option is 'fatigue/fell asleep'. Second, a proxy definition is applied to all crash reports. Those meeting the definition are considered SR and added to the police-reported SR crashes. Of the 65,204 vehicle operators involved in crashes 3449 were police-reported as SR. Analyses of these data found that male drivers aged 16-24 years within the first two years of unsupervised driving were most likely to have a SR crash. Collision with a stationary object was more likely in SR than in not-SR crashes. Using the proxy definition 9739 (14.9%) crashes were classified as SR. Using the proxy definition removes the findings that SR crashes are more likely to involve males and be of high severity. Additionally, proxy defined SR crashes are no less likely at intersections than not-SR crashes. When interpreting crash data it is important to understand the implications of SR identification because strategies aimed at reducing the road toll are informed by such data. Without the correct interpretation, funding could be misdirected. Improving sleepiness identification should be a priority in terms of both improvement to police and proxy reporting. PMID- 26666370 TI - Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines. AB - S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn's disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO2). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman's method, and the amount of NO abducted on the polymer was calculated using the Griess-Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 +/- 21 MUmol/g for SNA F1 and 468 +/- 23 MUmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 MUM. PMID- 26666371 TI - Optimization of radotinib doses for the treatment of Asian patients with chronic myelogenous leukemia based on dose-response relationship analyses. AB - A fixed dose regimen for tyrosine kinase inhibitors (TKIs) is postulated to be responsible for variable safety outcomes in the treatment of chronic myelogenous leukemia (CML). The objective of this study was to explore an optimal dosing regimen for a TKI, radotinib, to improve its safety profile. Clinical data were obtained from a Phase 2 study of fixed-dose radotinib in 77 Asian patients with CML. The magnitude of radotinib dose adjusted for patient's body weight (Dose/BW) and the probability of dose-limiting toxicity (DLT) demonstrated a positive association (Logit[P] = 0.86*[Dose/BW]-4.45, p = 0.001). There was a significant difference in the Kaplan-Meier curves for time to first DLT between the patient subgroups of Dose/BW <6 and >=6 mg/kg (259 versus 83 days). Consequently, a two tier weight-based dosing regimen may improve the safety of radotinib: 300 mg or 400 mg twice daily for patients weighing <=65 or >65 kg, respectively. PMID- 26666372 TI - Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan. AB - OBJECTIVE: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. METHOD: A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q - 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. RESULTS: Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q - 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype "AAGTCG" in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). CONCLUSION: These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan. PMID- 26666373 TI - Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5 transfected cells. AB - BACKGROUND: Previously, we have demonstrated that human ABCB5 is a full-sized ATP binding cassette transporter that shares strong homology with ABCB1/P glycoprotein. ABCB5-transfected cells showed resistance to taxanes and anthracyclines. Herein, we further screened ABCB5 substrates, and explored the mechanism of resistance. METHODS: Sensitivity of the cells to test compounds was evaluated using cell growth inhibition assay. Cellular levels of buthionine sulfoximine (BSO), glutathione and amino acids were measured using HPLC and an enzyme-based assay. Cellular and vesicular transport of glutathione was evaluated by a radiolabeled substrate. Expression levels of glutathione-metabolizing enzymes were assessed by RT-PCR. RESULTS: Human ABCB5-transfected 293/B5-11 cells and murine Abcb5-transfected 293/mb5-8 cells showed 6.5- and 14-fold higher resistance to BSO than the mock-transfected 293/mock cells, respectively. BSO is an inhibitor of gamma-glutamylcysteine ligase (GCL), which is a key enzyme of glutathione synthesis. 293/B5-11 and 293/mb5-8 cells also showed resistance to methionine sulfoximine, another GCL inhibitor. A cellular uptake experiment revealed that BSO accumulation in 293/B5-11 and 293/mb5-8 cells was similar to that in 293/mock cells, suggesting that BSO is not an ABCB5 substrate. The cellular glutathione content in 293/B5-11 and 293/mb5-8 cells was significantly higher than that in 293/mock cells. Evaluation of the BSO effect on the cellular glutathione content showed that compared with 293/mock cells the BSO concentration required for a 50 % reduction in glutathione content in 293/B5-11 and 293/mb5-8 cells was approximately 2- to 3-fold higher. This result suggests that the BSO resistance of the ABCB5- and Abcb5-transfected cells can be attributed to the reduced effect of BSO on the transfectants. Cellular and vesicular transport assays showed that the transport of radiolabeled glutathione in 293/B5-11 cells was similar to that in 293/mock cells. The mRNA expression of genes encoding glutathione-metabolizing enzymes in 293/B5-11 cells was similar to that in 293/mock cells. The cellular content of Glu, a precursor of glutathione, in 293/B5-11 and 293/mb5-8 cells was higher than that in 293/mock cells. CONCLUSIONS: ABCB5/Abcb5-transfected cells showed resistance to BSO, which is not a substrate of ABCB5. Our results suggest that ABCB5/Abcb5 upregulates cellular glutathione levels to protect cells from various poisons. PMID- 26666375 TI - Organomineral Interactions and Herbicide Sorption in Brazilian Tropical and Subtropical Oxisols under No-Tillage. AB - We evaluated the effects of the soil organic matter (SOM) composition, distribution between soil aggregates size, and their interactions with the mineral phase on herbicide sorption (alachlor, bentazon, and imazethapyr) in tropical and subtropical Oxisols under no-till systems (NT). Using soil physical fractionation approach, sorption experiments were performed on whole soils and their aggregates. SOM chemistry was assessed by CP/MAS (13)C NMR. The lower sorption observed in tropical soils was attributed to the greater blockage of SOM sorption sites than in subtropical soils. When these sites were exposed upon physical fractionation, sorption of the three herbicides in tropical soils increased, especially for imazethapyr. High amounts of poorly crystallized sesquioxides in these soils may have contributed to masking of sorption sites, indicating that organomineral interactions may lead to blockage of sorption sites on SOM in tropical soils. PMID- 26666374 TI - Evaluation of acute effect of light-emitting diode (LED) phototherapy on muscle deoxygenation and pulmonary oxygen uptake kinetics in patients with diabetes mellitus: study protocol for a randomized controlled trial. AB - BACKGROUND: Type 2 diabetes mellitus (DM) is responsible for a significant reduction in the quality of life due to its negative impact on functional capacity. Cardiopulmonary fitness impairment in DM patients has been associated with limited tissue oxygenation. Phototherapy is widely utilized to treat several disorders due to expected light-tissue interaction. This type of therapy may help to improve muscular oxygenation, thereby increasing aerobic fitness and functional capacity. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled crossover trial approved by the Ethics Committee of the Federal University of Sao Carlos and registered at ClinicalTrials.gov. Four separate tests will be performed to evaluate the acute effect of phototherapy. All participants will receive both interventions in random order: light-emitting diode therapy (LEDT) and placebo, with a minimum 14-day interval between sessions (washout period). Immediately after the intervention, participants will perform moderate constant workload cycling exercise corresponding to 80 % of the pulmonary oxygen uptake [Formula: see text] during the gas exchange threshold (GET). LEDT will be administered with a multidiode cluster probe (50 GaAIA LEDs, 850 etam, 75 mW each diode, and 3 J per point) before each exercise session. Pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure will be measured using a computerized metabolic cart, a near-infrared spectrometer, an electrocardiogram, and a photoplethysmography system, respectively. DISCUSSION: The main objective of this study is to evaluate the acute effects of muscular pre-conditioning using LED phototherapy on pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure dynamics during dynamic moderate exercise. We hypothesize that phototherapy may be beneficial to optimize aerobic fitness in the DM population. Data will be published after the study is completed. TRIAL REGISTRATION: Registered at ClinicalTrials.gov under trial number NCT01889784 (date of registration 5 June 2013). PMID- 26666376 TI - A qualitative study of older adults seeking appropriate treatment to self-manage their chronic pain in rural North-East Thailand. AB - BACKGROUND: Many older adults suffer from chronic pain which decreases their functional capacity and reduces quality of life. Health behaviours and self-care during chronic illness and chronic pain can exert an important influence on health outcomes. The aims of this study were to (a) understand how older adult Thai individuals seek appropriate treatment to self-manage their chronic pain, and (b) to identify factors that contribute to effective pain self-management. METHODS: Qualitative interviews were conducted with 32 older adults living in villages in north-east Thailand. Observations were also conducted with consenting individuals. Most interviews were audio-recorded and transcripts were coded and analysed using a grounded theory approach. RESULTS: Six contextual determinants affected the way participants choose to self-manage their chronic pain, including: priority accorded to pain management; information and resource seeking skills; critical appraisal skills; access to pain-related information; access to treatment; and satisfaction and preferences for practitioners. Participants used several strategies to inform and develop their self-management plans: accessing and responding to information, sourcing resources, trial and error, evaluating treatment and evaluating practitioners. CONCLUSIONS: Attempts to increase accessibility, affordability and acceptability of pain treatment can promote pain self-management in older Thais. These findings have important implications for health professionals and government organisations seeking to enhance the self management of pain and quality of life in this population. PMID- 26666377 TI - Phenolic compounds from the twigs and leaves of Tara (Caesalpinia spinosa). AB - Two new homoisoflavans, 4'-hydroxy-7-methoxy-3-benzyl-2H-chromene (1) and 3,4-cis di-O-3-hydroxy-7-methoxy-3-(4-hydroxybenzyl)-4-ethoxychroman (2), one new coumarin, 7-methoxy-3-(4-hydroxybenzyl)coumarin (4), together with seven known phenolic compounds, bonducellin (3), anemarcoumarin A (5), (+)-syringaresinol (6), curuilignan D (7), scopoletin (8), and p-hydroxybenzaldehyde (9), were isolated from Tara (Caesalpinia spinosa Kuntze). The structures of the new compounds were characterized from their 1D and 2D NMR spectral data. All the compounds were isolated from this plant for the first time. PMID- 26666378 TI - Effect of silver nanoparticles on Candida albicans biofilms: an ultrastructural study. AB - BACKGROUND: Candida albicans is the most common pathogenic fungus isolated in bloodstream infections in hospitalized patients, and candidiasis represents the fourth most common infection in United States hospitals, mostly due to the increasing numbers of immune- and medically-compromised patients. C. albicans has the ability to form biofilms and morphogenetic conversions between yeast and hyphal morphologies contribute to biofilm development and represent an essential virulence factor. Moreover, these attached communities of cells are surrounded by a protective exopolymeric matrix that effectively shelters Candida against the action of antifungals. Because of dismal outcomes, novel antifungal strategies, and in particular those targeting biofilms are urgently required. As fungi are eukaryotic, research and development of new antifungal agents has been difficult due to the limited number of selective targets, also leading to toxicity. RESULTS: By microwave-assisted techniques we obtained pure 1 nm spherical silver nanoparticles ideal for their potential biological applications without adding contaminants. A phenotypic assay of C. albicans demonstrated a potent dose dependent inhibitory effect of silver nanoparticles on biofilm formation, with an IC50 of 0.089 ppm. Also silver nanoparticles demonstrated efficacy when tested against pre-formed C. albicans biofilms resulting in an IC50 of 0.48 ppm. The cytotoxicity assay resulted in a CC50 of 7.03 ppm. The ultrastructural differences visualized under SEM with silver nanoparticles treatment were changes in the surface appearance of the yeast from smooth to rough thus indicating outer cell wall damage. On the fungal pre-formed biofilm true hyphae was mostly absent, as filamentation was inhibited. TEM measurement of the cell-wall width of C. albicans after treatment resulted in significant enlargement (206 +/- 11 nm) demonstrating membrane permeabilization. CONCLUSIONS: Our results demonstrate that silver nanoparticles are potent inhibitors of C. albicans biofilm formation. SEM observations are consistent with an overall loss of structure of biofilms mostly due to disruption of the outer cell membrane/wall and inhibition of filamentation.TEM indicates the permeabilization of the cell wall and subsequent disruption of the structural layers of the outer fungal cell wall. The anti biofilm effects are via cell wall disruption. PMID- 26666379 TI - Causes of treatment failure for hepatitis C in the era of direct-acting antiviral therapy. AB - Hepatitis C therapy in the era of the newer direct-acting antiviral agents has radically changed our treatment schemes by achieving very high rates of sustained virological response. However, treatment with direct antiviral agents fails in a subgroup of patients. This group of so-called difficult-to-treat individuals is the subject of this paper, which reviews the causes of virological failure, their clinical implications, and some final recommendations. PMID- 26666380 TI - Predicting Risk Versus Predicting Potential Survival Benefit Using 123I-mIBG Imaging in Patients With Systolic Dysfunction Eligible for Implantable Cardiac Defibrillator Implantation: Analysis of Data From the Prospective ADMIRE-HF Study. AB - BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine ((123)I-mIBG) imaging improves prognostication in patients with left ventricular (LV) dysfunction. Whether (123)I-mIBG can identify optimal candidates for implantable cardiac defibrillator (ICD) placement is unclear. We examined whether (123)I-mIBG enhances risk assessment and identifies patients with enhanced survival with ICD in a patient cohort with reduced LV function who were candidates for ICD implantation. METHODS AND RESULTS: We identified 777 patients (66 sites, 12 countries) without ICD at the time of enrollment in Adreview Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) and index (123)I-mIBG study. Patients completed prescribed study protocol and follow-up. Heart-to-mediastinum (H/M) ratio was determined from (123)I-mIBG results. Survival modeling used a Cox proportional hazards mixed-effects model, including a propensity score, to adjust for nonrandomized ICD implantation after (123)I-mIBG. All-cause death occurred in 75 patients (9.6%), and 196 (25%) patients had ICD implantation on follow-up. After adjusting for multiple factors, although the H/M ratio added incremental prognostic value and enhanced reclassification, neither H/M results, BNP levels, nor left ventricular ejection fraction interacted with ICD use in the survival model, indicating that these variables did not identify patients with enhanced survival with ICD implantation. Nonetheless, H/M results did identify the number of lives saved by ICD use per 100 treated. CONCLUSIONS: We found that although (123)I-mIBG imaging enhances the risk stratification of patients with left ventricular dysfunction who are ICD candidates, it does not identify which patients may have improved survival with ICD placement. However, (123)I-mIBG identifies the absolute benefit gained with ICD use, thus may play a role in optimizing the cost-effectiveness of this intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00126425 and NCT00126438. PMID- 26666381 TI - Exercise-Induced Left Ventricular Remodeling Among Competitive Athletes: A Phasic Phenomenon. AB - BACKGROUND: Contemporary understanding of exercise-induced cardiac remodeling is based on cross-sectional data and relatively short duration longitudinal studies. Temporal progression of exercise-induced cardiac remodeling remains incompletely understood. METHODS AND RESULTS: A longitudinal repeated-measures study design using 2-dimensional and speckle-tracking echocardiography was used to examine acute augmentation phase (AAP; 90 days) and more extended chronic maintenance phase (39 months) left ventricular (LV) structural and functional adaptations to endurance exercise training among competitive male rowers (n=12; age 18.6+/-0.5 years). LV mass was within normal limits at baseline (93+/-9 g/m(2)), increased after AAP (105+/-7 g/m(2); P=0.001), and further increased after chronic maintenance phase (113+/-10 g/m(2); P<0.001 for comparison to post-AAP). AAP LV hypertrophy was driven by LV dilation (DeltaLV end-diastolic volume, 9+/-3 mL/m(2); P=0.004) with stable LV wall thickness (DeltaLV wall thickness, 0.3+/ 0.1 mm; P=0.63). In contrast, chronic maintenance phase LV hypertrophy was attributable to LV wall thickening (Delta LV wall thickness, 1.1+/-0.4 mm; P=0.004) with stable LV chamber volumes (DeltaLV end-diastolic volume, 1+/-1 mL/m(2); P=0.48). Early diastolic peak tissue velocity increased during AAP ( 11.7+/-1.9 versus -13.6+/-1.3 cm/s; P<0.001) and remained similarly increased after chronic maintenance phase. CONCLUSIONS: In a small sample of competitive endurance athletes, exercise-induced cardiac remodeling follows a phasic response with increases in LV chamber size, early diastolic function, and systolic twist in an acute augmentation phase of exercise training. This is followed by a chronic phase of adaptation characterized by increasing wall thickness and regression in LV twist. Training duration is a determinant of exercise-induced cardiac remodeling and has implications for the assessment of myocardial structure and function in athletes. PMID- 26666382 TI - Decision Making for Implantable Cardioverter Defibrillator Implantation: Is There a Role for Neurohumoral Imaging? PMID- 26666383 TI - Exercise-Induced Cardiac Remodeling: Not a Case of One Size Fits All. PMID- 26666384 TI - Effect of interactions of polymorphisms in the Melanocortin-4 receptor gene with dietary factors on the risk of obesity and Type 2 diabetes: a systematic review. AB - AIM: To perform a systematic review of the effect of interaction between Melanocortin-4 receptor (MC4R) single nucleotide polymorphisms and diet on the development of obesity and Type 2 diabetes. BACKGROUND: Environmental factors, such as nutrient intakes or feeding behaviours, can modulate the association of polymorphism in the MC4R gene with obesity and Type 2 diabetes mellitus. METHODS: A systematic literature search was conducted in the PubMed, Scopus and Google Scholar databases, with a combination of the following keywords: Diet*, nutr*, melanocortin receptor, melanocortin 4 receptor and MC4R. To assess the quality of observational studies, we used a 12-item quality checklist, derived from the STREGA statement. RESULTS: A total of 14 articles were selected based on the inclusion and exclusion criteria. Consumption of highly salty foods and adherence to a Mediterranean dietary pattern can modulate the association between MC4R polymorphisms and the risk of obesity or Type 2 diabetes. Despite the highly contradictory results of intervention studies, after short-term lifestyle interventions, children with variant alleles of MC4R single nucleotide polymorphisms can lose more body weight, compared with non-carriers, although they may have difficulty in maintaining this weight loss in the long-term. To interpret the results of studies on adults, we need further studies. CONCLUSIONS: The interaction between MC4R genes with dietary factors plays a significant role in the development of obesity or Type 2 diabetes phenotypes. Early detection of MC4R risk alleles in individuals and modification of their diet based on these results could be an efficient strategy to prevent obesity or diabetes in these subgroups. PMID- 26666386 TI - Stress. PMID- 26666385 TI - Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach. AB - BACKGROUND: Idiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF's most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome. METHODS: We studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression. RESULTS: Twenty-four out of 85 admissions (28%) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50% survived; 3 out of 12 (25%) in the group previously treated with immunosuppression whereas nine out of 12 (75%) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3% survived; 3 out of 6 (50%) in the never treated group whereas three out of 11 (27.3%) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83% 1-year survival. CONCLUSIONS: By applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event. PMID- 26666387 TI - beta-Bisabolene, a Sesquiterpene from the Essential Oil Extract of Opoponax (Commiphora guidottii), Exhibits Cytotoxicity in Breast Cancer Cell Lines. AB - The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography-mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; beta-bisabolene and an alcoholic analogue, alpha-bisabolol, were tested for their ability to selectively kill breast cancer cells. Only beta-bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 ug/ml, MG1361: 65.49 ug/ml, 4T1: 48.99 ug/ml) and human breast cancer cells (IC50 in normal MCF-10A: 114.3 ug/ml, MCF-7: 66.91 ug/ml, MDA-MB 231: 98.39 ug/ml, SKBR3: 70.62 ug/ml and BT474: 74.3 ug/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V propidium iodide and caspase-3/7 activity assay. beta-bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of beta-bisabolene in the treatment of breast cancers. PMID- 26666388 TI - Correlation between lignin physicochemical properties and inhibition to enzymatic hydrolysis of cellulose. AB - Using isolated organosolv lignins from hardwood poplar and softwood lodgepole pine with varied physicochemical properties (molecular weight, aliphatic hydroxyl, phenolic hydroxyl, and hydrophobicity), the inhibitory effect of the lignins on enzymatic hydrolysis of cellulose was investigated and the relationship between lignin properties and the inhibitory effect was elucidated. The results indicated that the lignin inhibition to enzymatic hydrolysis of cellulose was closely related to the hydrophobicity and the phenolic hydroxyl groups of the lignin. The overall hydrophobicity of the lignin quantified by contact angle could serve as a predictor of the inhibitory effect of lignin. Hydrophilic modification of the lignin by carboxylation and sulfonation reduced the hydrophobicity by 22-30% and thereby removed the lignin inhibition by 76-96%. Phenolic hydroxyl group was a crucial factor affecting the inhibitory effect of lignin. Blocking free phenolic hydroxyl group by chemical reaction such as hydroxypropylation significantly (65-91%) reduced the inhibitory effect of lignin. Biotechnol. Bioeng. 2016;113: 1213-1224. (c) 2015 Wiley Periodicals, Inc. PMID- 26666389 TI - Effect of Storage Time on Bond Strength and Nanoleakage Expression of Universal Adhesives Bonded to Dentin and Etched Enamel. AB - PURPOSE: To investigate bond strength and nanoleakage expression of universal adhesives (UA) bonded to dentin and etched enamel. METHODS: Extracted human third molars were sectioned and ground to obtain flat surfaces of dentin (n = 36) and enamel (n = 48). Dentin and etched enamel surfaces were bonded with one of two UAs, All-Bond Universal (ABU) or Scotchbond Universal (SBU); or a two-step self etching adhesive, Clearfil SE Bond (CSEB). A hydrophobic bonding resin, Adper Scotchbond Multi-Purpose Bond (ASMP Bond) was applied only on etched enamel. Following each bonding procedure, resin composite blocks were built up incrementally. The specimens were sectioned and subjected to microtensile bond strength (MTBS) testing after 24 hours or one year water storage, or immersed into ammoniacal silver nitrate solution after aging with 10,000 thermocycles and observed using scanning electron microscopy. The percentage distribution of silver particles at the adhesive/tooth interface was calculated using digital image-analysis software. RESULTS: The MTBS (CSEB = SBU > ABU, for dentin; and CSEB > ABU = SBU = ASMP Bond, for etched enamel) differed significantly between the adhesives after 24 hours. After one year, MTBS values were reduced significantly within the same adhesive for both substrates (analysis of variance, Bonferroni post hoc, p<0.05), and no significant differences were found among the adhesives for etched enamel. Silver particles could be detected within the adhesive/dentin interface of all specimens tested. Kruskal-Wallis mean ranks for nanoleakage in ABU, SBU, and CSEB were 16.9, 18.5 and 11, respectively (p>0.05). CONCLUSIONS: In the short term, MTBS values were material and dental-substrate dependent. After aging, a decrease in bonding effectiveness was observed in all materials, with nanoleakage at the adhesive/dentin interface. The bonding of the UAs was equal or inferior to that of the conventional restorative systems when applied to either substrate and after either storage period. PMID- 26666390 TI - Effect of Polishing Systems on Surface Roughness and Topography of Monolithic Zirconia. AB - This study evaluated the effect of different chairside polishing systems on the surface roughness and topography of monolithic zirconia. Thirty-five monolithic zirconia specimens (Lava PLUS, 3M ESPE) were fabricated and divided into five groups of seven and polished with the following: Group 1 (WZ)-Dura white stone followed by Shofu zirconia polishing kit; Group 2 (SZ)-Shofu zirconia polishing kit; Group 3 (CE)-Ceramiste porcelain polishers; Group 4 (CM)-Ceramaster porcelain polishers; and Group 5 (KZ)-Komet ZR zirconia polishers. All specimens were ground with a fine-grit diamond bur prior to polishing procedures to simulate clinical finishing. Baseline and post-polishing profilometric readings were recorded and delta Ra values (difference in mean surface roughness before and after polishing) were computed and analyzed using one-way analysis of variance and Scheffe post hoc test (p<0.05). Representative scanning electron microscopy (SEM) images of the ground but unpolished and polished specimens were acquired. Delta Ra values ranged from 0.146 for CE to 0.400 for KZ. Delta Ra values for KZ, WZ, and SZ were significantly greater than for CE. Significant differences in delta Ra values were also observed between KZ and CM. The SEM images obtained were consistent with the profilometric findings. Diamond impregnated polishing systems were more effective than silica carbide-impregnated ones in reducing the surface roughness of ground monolithic zirconia. PMID- 26666391 TI - Chemo- and Regioselective Hydrogenolysis of Diaryl Ether C-O Bonds by a Robust Heterogeneous Ni/C Catalyst: Applications to the Cleavage of Complex Lignin Related Fragments. AB - We report the chemo- and regioselective hydrogenolysis of the C-O bonds in di ortho-substituted diaryl ethers under the catalysis of a supported nickel catalyst. The catalyst comprises heterogeneous nickel particles supported on activated carbon and furnishes arenes and phenols in high yields without hydrogenation. The high thermal stability of the embedded metal particles allows C-O bond cleavage to occur in highly substituted diaryl ether units akin to those in lignin. Preliminary mechanistic experiments show that this catalyst undergoes sintering less readily than previously reported catalyst particles that form from a solution of [Ni(cod)2]. PMID- 26666392 TI - A combined system of microbial fuel cell and intermittently aerated biological filter for energy self-sufficient wastewater treatment. AB - Energy self-sufficiency is a highly desirable goal of sustainable wastewater treatment. Herein, a combined system of a microbial fuel cell and an intermittently aerated biological filter (MFC-IABF) was designed and operated in an energy self-sufficient manner. The system was fed with synthetic wastewater (COD = 1000 mg L(-1)) in continuous mode for more than 3 months at room temperature (~25 degrees C). Voltage output was increased to 5 +/- 0.4 V using a capacitor-based circuit. The MFC produced electricity to power the pumping and aeration systems in IABF, concomitantly removing COD. The IABF operating under an intermittent aeration mode (aeration rate 1000 +/- 80 mL h(-1)) removed the residual nutrients and improved the water quality at HRT = 7.2 h. This two-stage combined system obtained 93.9% SCOD removal and 91.7% TCOD removal (effluent SCOD = 61 mg L(-1), TCOD = 82.8 mg L(-1)). Energy analysis indicated that the MFC unit produced sufficient energy (0.27 kWh m(-3)) to support the pumping system (0.014 kWh m(-3)) and aeration system (0.22 kWh m(-3)). These results demonstrated that the combined MFC-IABF system could be operated in an energy self-sufficient manner, resulting to high-quality effluent. PMID- 26666393 TI - Dissociating sensory from decision processes in human perceptual decision making. AB - A key question within systems neuroscience is how the brain translates physical stimulation into a behavioral response: perceptual decision making. To answer this question, it is important to dissociate the neural activity underlying the encoding of sensory information from the activity underlying the subsequent temporal integration into a decision variable. Here, we adopted a decoding approach to empirically assess this dissociation in human magnetoencephalography recordings. We used a functional localizer to identify the neural signature that reflects sensory-specific processes, and subsequently traced this signature while subjects were engaged in a perceptual decision making task. Our results revealed a temporal dissociation in which sensory processing was limited to an early time window and consistent with occipital areas, whereas decision-related processing became increasingly pronounced over time, and involved parietal and frontal areas. We found that the sensory processing accurately reflected the physical stimulus, irrespective of the eventual decision. Moreover, the sensory representation was stable and maintained over time when it was required for a subsequent decision, but unstable and variable over time when it was task irrelevant. In contrast, decision-related activity displayed long-lasting sustained components. Together, our approach dissects neuro-anatomically and functionally distinct contributions to perceptual decisions. PMID- 26666394 TI - Class I and II HLA antibodies in pediatric patients with thalassemia major. AB - BACKGROUND: HLA alloimmunization is a potential complication of red blood cell (RBC) transfusion with detrimental consequences for future organ or hematopoietic stem cell transplantation. STUDY DESIGN AND METHODS: The study aimed to determine the prevalence and specificity of HLA antibodies among pediatric patients with thalassemia major (TM) and antibody changes over time while on leukoreduced chronic transfusion therapy. HLA antibodies were measured at two or more time points in children and young adults ages 3 to 21 years with TM. HLA Class I and II antibodies were measured by FlowPRA screening. Positive screening assays were confirmed with LabScreen single-antigen bead assays for antibody specificity. RESULTS: HLA antibodies were detected in 10 of 19 (53%) subjects: seven of 19 (37%) with HLA Class I and II antibodies, two of 19 (11%) with only HLA Class I antibodies, and one of 19 (5%) with only HLA Class II antibodies. Subjects with HLA antibodies were older (14.6 years vs. 7.1 years, p = 0.05), predominantly male (80%), and more likely to have a remote history of nonleukoreduced transfusions (p = 0.057). Median time between testing was 3.7 years. De novo HLA antibodies were detected in two of 11 patients who initially had negative panel reactive antibody screens, while one subject lost detection of Class II antibody. Two of seven patients with HLA antibodies had antibodies to self-HLA. CONCLUSION: HLA antibodies have a high prevalence in TM patients and may be associated with nonleukoreduced transfusions and older age. For such patients, antibody identification will be useful if subsequent organ or stem cell transplantation is needed. PMID- 26666396 TI - Degassing during quiescence as a trigger of magma ascent and volcanic eruptions. AB - Understanding the mechanisms that control the start-up of volcanic unrest is crucial to improve the forecasting of eruptions at active volcanoes. Among the most active volcanoes in the world are the so-called persistently degassing ones (e.g., Etna, Italy; Merapi, Indonesia), which emit massive amounts of gas during quiescence (several kilotonnes per day) and erupt every few months or years. The hyperactivity of these volcanoes results from frequent pressurizations of the shallow magma plumbing system, which in most cases are thought to occur by the ascent of magma from deep to shallow reservoirs. However, the driving force that causes magma ascent from depth remains unknown. Here we demonstrate that magma ascent can be triggered by the passive release of gas during quiescence, which induces the opening of pathways connecting deep and shallow magma reservoirs. This top-down mechanism for volcanic eruptions contrasts with the more common bottom-up mechanisms in which magma ascent is only driven by processes occurring at depth. A cause-effect relationship between passive degassing and magma ascent can explain the fact that repose times are typically much longer than unrest times preceding eruptions, and may account for the so frequent unrest episodes of persistently degassing volcanoes. PMID- 26666395 TI - Multiple tobacco product use among young adult bar patrons in New Mexico. AB - INTRODUCTION: Use of non-cigarette tobacco products is common, and e-cigarette use is increasing among young adults. We aimed to identify use of other tobacco products among young adult bar patrons in the context of a bar-based intervention to decrease cigarette smoking. METHODS: 2291 cross-sectional surveys were collected from young adults in bars in Albuquerque, New Mexico using time location sampling between 2011 and 2013 (N=1142 in 2011, N=1149 in 2012-2013), 2 and 3years into an intervention to reduce cigarette use, and analyzed in 2014 2015. Participants reported current (i.e. past 30-day) use of cigarettes, snus, dip, cigarillos, hookah, and e-cigarettes, demographics, and tobacco-related attitudes. Multiple imputation was used to account for planned missing data. Logistic regression determined correlates of multiple tobacco product use. RESULTS: Cigarette smoking in the population decreased during the intervention from 43% to 37%. Over 60% of current cigarette smokers reported poly-use, most frequently with e-cigarettes (46%) and hookah (44%), followed by cigarillos (24%), dip (15%), and snus (14%) in 2012-2013. Among cigarette smokers, current e cigarette use increased, while use of other products decreased during the intervention. Odds of poly-use (versus smoking cigarettes only) were greater among males and those reporting past 30-day binge drinking, and lower in those who strongly believed secondhand smoke exposure is harmful. CONCLUSIONS: Among young adult bar patrons in Albuquerque, New Mexico, most cigarette smokers reported currently using at least one other tobacco product. Public health interventions should address use of all tobacco products, use of which may rise despite decreased cigarette use. PMID- 26666398 TI - Recent Advances in Topical Ocular Drug Delivery. AB - Topical ocular drug delivery has been considered to be an ideal route of administration for treatment of ocular diseases related to the anterior segment of the eye. However, topical ocular delivery is a challenging task because of barriers such as nasolacrimal drainage, corneal epithelium, blood-ocular barriers, and metabolism in the eye. Approaches to improve ocular bioavailability include physical approaches such as formulations of drugs as solutions (Zymaxid(TM)), suspensions (Zigran((r))), gels (Akten((r))) and chemical approaches such as prodrugs (Xalatan(TM)), chemical delivery systems, and soft drugs. The purpose of this review article is to summarize recent advances in topical drug delivery to the anterior segment of the eye. Functional transporters in the corneal epithelium were also discussed as they provide prospects in topical ocular delivery. In addition to conventional delivery systems, novel delivery systems involving nanocarriers were also investigated for topical ocular delivery. Furthermore, due to increased interest, gene therapy applications of topical ocular delivery of genes to the anterior segment of the eye were also discussed. Research in topical ocular delivery is active for more than 50 years and proven to be advantageous for the treatment of many ocular diseases. However, there is scope for innovation in topical drug delivery to develop delivery systems with a high patient safety profile and compliance for effective clinical usefulness. PMID- 26666399 TI - Real-Space Mapping of the Chiral Near-Field Distributions in Spiral Antennas and Planar Metasurfaces. AB - Chiral antennas and metasurfaces can be designed to react differently to left- and right-handed circularly polarized light, which enables novel optical properties such as giant optical activity and negative refraction. Here, we demonstrate that the underlying chiral near-field distributions can be directly mapped with scattering-type scanning near-field optical microscopy employing circularly polarized illumination. We apply our technique to visualize, for the first time, the circular-polarization selective nanofocusing of infrared light in Archimedean spiral antennas, and explain this chiral optical effect by directional launching of traveling waves in analogy to antenna theory. Moreover, we near-field image single-layer rosette and asymmetric dipole-monopole metasurfaces and find negligible and strong chiral optical near-field contrast, respectively. Our technique paves the way for near-field characterization of optical chirality in metal nanostructures, which will be essential for the future development of chiral antennas and metasurfaces and their applications. PMID- 26666397 TI - Urinary heavy metals in Hispanics 40-85 years old in Dona Ana County, New Mexico. AB - Exposure to As, Cd, Pb, and U among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults aged 40-85 years. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (p < .05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private-well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population. PMID- 26666400 TI - Assessment of Effectiveness of Control Strategies Against Simulated Outbreaks of Highly Pathogenic Avian Influenza in Ontario, Canada. AB - The North American Animal Disease Spread Model (NAADSM) is a stochastic model framework developed to simulate the spread of highly contagious diseases of livestock and poultry, such as foot-and-mouth disease and highly pathogenic avian influenza (HPAI). The objective of this study was to make recommendations on the most effective HPAI control policy for Canada, specifically, on the effect of different speeds of detection, effectiveness of movement restrictions and stamping-out and ring-culling strategies on the magnitude of an HPAI outbreak. In addition, the effect of introduction of infection in a range of multiple farms simultaneously was also evaluated. A total of 21 060 scenarios, defined as different combinations of parameters for various epidemiological conditions and control measures, were created to simulate the number of poultry flocks that would become infected as a result of an incursion of HPAI. Each scenario was parameterized in NAADSM and replicated 1000 times, generating the median number of flocks infected at the end of the simulated outbreak for each scenario. Negative binomial regression analysis was used to model significant explanatory variables of the median number of flocks infected at the end of each simulated outbreak for each of the 21 060 scenarios. The final model included the following explanatory variables: number and type initially infected flock(s), density of flocks within the county where the initially infected flock(s) was located, probability of transmission through indirect contact, subclinical spread of the infection, speed of detection and a two-way interaction between intensity of bird destruction strategy and movement restriction effectiveness to reduce transmission through direct and indirect contacts. The modelling results suggested that stamping out of the detected infected flocks, without ring culling, in combination with effective movement restrictions on direct and indirect contacts, would be the most appropriate policy for Ontario. PMID- 26666401 TI - Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome. AB - We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1alpha, IL-6, IL-10, chemokine (C C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy. PMID- 26666402 TI - Mechanisms of HIV-1 Nucleocapsid Protein Inhibition by Lysyl-Peptidyl Anthraquinone Conjugates. AB - The Nucleocapsid protein NCp7 (NC) is a nucleic acid chaperone responsible for essential steps of the HIV-1 life cycle and an attractive candidate for drug development. NC destabilizes nucleic acid structures and promotes the formation of annealed substrates for HIV-1 reverse transcription elongation. Short helical nucleic acid segments bordered by bulges and loops, such as the Trans-Activation Response element (TAR) of HIV-1 and its complementary sequence (cTAR), are nucleation elements for helix destabilization by NC and also preferred recognition sites for threading intercalators. Inspired by these observations, we have recently demonstrated that 2,6-disubstituted peptidyl-anthraquinone conjugates inhibit the chaperone activities of recombinant NC in vitro, and that inhibition correlates with the stabilization of TAR and cTAR stem-loop structures. We describe here enhanced NC inhibitory activity by novel conjugates that exhibit longer peptidyl chains ending with a conserved N-terminal lysine. Their efficient inhibition of TAR/cTAR annealing mediated by NC originates from the combination of at least three different mechanisms, namely, their stabilizing effects on nucleic acids dynamics by threading intercalation, their ability to target TAR RNA substrate leading to a direct competition with the protein for the same binding sites on TAR, and, finally, their effective binding to the NC protein. Our results suggest that these molecules may represent the stepping stone for the future development of NC-inhibitors capable of targeting the protein itself and its recognition site in RNA. PMID- 26666403 TI - Diabetes-dependent quality of life (ADDQOL) and affecting factors in patients with diabetes mellitus type 2 in Greece. AB - BACKGROUND: Diabetes mellitus type 2 (T2D) is a chronic metabolic disease with a great impact on health status and quality of life (QoL) in terms of physical, social, and psychological well-being. The aim of the present study was to measure diabetes-dependent QoL and affecting factors in patients with T2D. METHODS: Study population was consisted by 258 subjects with T2D attending diabetic outpatient clinics of General Hospitals of Piraeus "Tzaneio" and Nikaia "Ag.Panteleimon" during September-December 2014. The Audit of Diabetes-Dependent Quality of Life questionnaire was carried out in all study participants. RESULTS: Diabetes mellitus type 2 had a negative impact to QoL in 37.3 % of the study participants while 32.9 % believed that their life would have been better without the presence of T2D. Diabetes had negative impact on working life (-1.3 +/- 0.6), health status (-1.3 +/- 0.2), family (-1.3 +/- 0.6) and sexual life (-1.3 +/- 0.3), future perspectives (-1.3 +/- 0.4) and dietary habits (-1.7 +/- 0.2). The results of logistic regression analysis showed that QoL was related with age [odds ratio (OR) 0.94, 95 % confidence intervals (CIs) 0.91-1.98, P = 0.008] and marital status (OR 0.43, 95 %CIs 0.21-0.90, P = 0.03). CONCLUSIONS: The results of the present study showed that T2D per se has a negative impact to patient's QoL most of all affecting working life, health status, family and sexual life, future perspectives and dietary habits. Age and marital status were the only determinants of QoL. PMID- 26666404 TI - Cervical stenosis in spinal cord injury and disorders. AB - CONTEXT/OBJECTIVE: The purpose of this study was to characterize etiologies of spinal cord injury and disorders (SCI/D) in persons with and without cervical stenosis/spondylosis (CSS) and to describe clinical characteristics and underlying comorbidities in these populations. DESIGN AND SETTING: We reviewed administrative data for 1954 Veterans who had onset of traumatic or non-traumatic tetraplegia during FY 1999-2007. This included 1037 with a diagnosis of CSS at or in the two years prior to SCI onset of SCI/D and 917 without a diagnosis of CSS. OUTCOME MEASURES: Demographics, etiologies of SCI/D and comorbidities by CSS status. RESULTS: Veterans with SCI/D and CSS were older, more likely to have incomplete injuries and more likely to be Black than those with SCI/D and no CSS. Of patients with traumatic etiologies for SCI, 35.1% had a diagnosis of CSS at the time of or in the 2 years prior to SCI onset. Of those with tetraplegia due to falls, 40.0% had CSS, whereas for other known traumatic etiologies the percentages with CSS were lower: vehicular (25.0%); sports (16.1%); and acts of violence (10.2%). Total comorbidity scores measured by the Charlson co morbidity index and CMS Hierarchical Condition Category (CMS-HCC) were higher in those with CSS and SCI/D compared to those with SCI/D without CSS (P < 0.0001 respectively). CONCLUSIONS: CSS is commonly present in patients with new traumatic tetraplegia. Falls are a particularly important potentially modifiable risk for SCI in patients with CSS. PMID- 26666405 TI - Exploring the impact of music concerts in promoting well-being in dementia care. AB - OBJECTIVES: This study explores the specific effects of live music concerts on the clients with dementia, their families and nursing staff/caregivers. METHODS: Researchers attended 22 concerts in care facilities in England and Japan. Interviews were carried out with clients with dementia, nursing staff and family members. Observations were also carried out before, during and after the concerts. All observations were recorded in field notes. RESULTS: The effect of the concerts in both countries was seen to be beneficial to all clients and nursing staff, whether or not they attended the concert. Interviews with clients with mild to mid-stage dementia noted increased levels of cooperation, interaction and conversation. Those with more advanced forms of dementia exhibited decreased levels of agitation and anti-social behaviour. Staff members reported increased levels of care, cooperation and opportunities for assessment. Family members noted an increase in the levels of well-being in their partner/parent as well as in themselves. The study also suggested that the knowledge of musical components, an awareness of the rules of music and specific musical preferences appear to remain well beyond the time when other cognitive skills and abilities have disappeared. CONCLUSIONS: This initial study provided some further indication in terms of the uses of music as a non-pharmacological intervention for those living with all stages of dementia. These included opportunities for assessment of physical abilities as well as facilitating an increasing level of care. PMID- 26666406 TI - Fucoxanthin Induced Suicidal Death of Human Erythrocytes. AB - BACKGROUND/AIMS: Fucoxanthin, a carotenoid isolated from brown seaweeds, induces suicidal death or apoptosis of tumor cells and is thus considered for the treatment or prevention of malignancy. In analogy to apoptosis of nucleated cell, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and activation of p38 kinase or protein kinase C. The present study explored, whether and how fucoxanthin induces eryptosis. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence and lipid peroxidation using BODIPY fluoresence. RESULTS: A 48 hours exposure of human erythrocytes to fucoxanthin significantly increased the percentage of annexin-V binding cells (>= 50 uM), significantly decreased average forward scatter (>= 25 uM), significantly increased hemolysis (>= 25 uM), significantly increased Fluo3 fluorescence (>= 50 uM), significantly increased lipid peroxidation, but did not significantly modify DCFDA fluorescence. The effect of fucoxanthin on annexin-V binding was significantly blunted, but not abolished by removal of extracellular Ca2+, and was insensitive to p38 kinase inhibitor skepinone (2 uM) and to protein kinase C inhibitor calphostin (100 nM). CONCLUSION: Fucoxanthin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry. PMID- 26666407 TI - How the substituents in corannulene and sumanene derivatives alter their molecular assemblings and charge transport properties?--A theoretical study with a dimer model. AB - The substituent effects on the structures, intermolecular interactions and charge transport properties of a series of corannulene and sumanene derivatives were investigated by DFT method. The intermolecular interaction energy and the potential energy surface of the dimers were also calculated and analyzed in detail, which showed several local energy minima and demonstrated the possible dimer structures in experiment. In addition, the reorganization energy, transfer integral, and carrier mobility were explored to measure the charge transport properties of these substituted corannulenes and sumanenes at different configurations for investigating the substituent effects. Our study is closely related to the experiment and previous theoretical investigation and provides a better understanding of the structure-property relationships for these substituted corannulenes and sumanenes. PMID- 26666408 TI - Preparation, characterization, and efficacy of thermosensitive liposomes containing paclitaxel. AB - To increase the anti-tumor activity of paclitaxel (PTX), novel temperature sensitive liposomes loading paclitaxel (PTX-TSL) were developed. In vitro, characteristics of PTX-TSL were evaluated. The mean particle diameter was about 100 nm, and the entrapment efficiency was larger than 95%. The phase-transition temperature of PTX-TSL determined by differential scanning calorimetry was about 42 degrees C. The result of in vitro drug release from PTX-TSL illustrated that release rate at 37 degrees C was obviously lower than that at 42 degrees C. Stability data indicated that the liposome was physically and chemically stable for at least 3 months at -20 degrees C. In vivo study, after three injections with hyperthermia in the xenograft lung tumor model, PTX-TSL showed distinguished tumor growth suppression, compared with non-temperature-sensitive liposome and free drug. The results of intratumoral drug concentration indicated that PTX-TSL combined with hyperthermia delivered more paxlitaxel into the tumor location than the other two paxlitaxel formulations. In summary, PTX-TSL combined with hyperthermia significantly inhibited tumor growth, due to the increased targeting efficiency of PTX to tumor tissues. Such approach may enhance the delivery efficiency of chemotherapeutics into solid tumors. PMID- 26666409 TI - Prostatectomy at high-volume centers improves outcomes and lowers the costs of care for prostate cancer. AB - BACKGROUND: High-volume surgeons with ?250 radical prostatectomies provide superior oncological outcomes as evidenced by a lower rate of PSA recurrence (PSAR). The financial benefits of performing prostatectomies at high-volume centers (HVC) are unexplored. METHODS: A base case--referent scenario--where the share of prostatectomies at high- and low-volume centers were evenly divided at 50% was defined. Additional scenarios with increasing shares of prostatectomies at HVC with 10% increments were also modeled. Using a lower probability of PSAR as the only advantage of more experienced surgeons, the savings that would result from fewer recurrences, avoidance of salvage radiation therapy (SRT) and management of fewer men with metastatic cancer were calculated. RESULTS: The savings associated with performing 80% of radical prostatectomy at HVC were $177, $357 and $559 per prostatectomy at 5, 10 and 20 years, respectively. These savings would offset referral costs of up to $1833 per prostatectomy referral at no additional total societal costs. Given the longer average biochemical failure free survival with prostatectomies at HVC, referral costs of more than $1833 may be cost effective. CONCLUSIONS: Under the conservative assumption of accounting for lower rates of PSAR as the only benefit of surgery in an HVC, performing prostatectomies at an HVC was associated with savings that may offset part of the initial referral costs. PMID- 26666411 TI - On gunboats and grand pianos: medical education exports and the long shadow of colonialism. PMID- 26666410 TI - Association of diet and lifestyle with chronic prostatitis/chronic pelvic pain syndrome and pain severity: a case-control study. AB - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common problem with unclear etiology. Some diet and lifestyle factors were thought to correlate with CP/CPPS, but studies comprehensively investigate this correlation are rarely available. The current study was conducted to determine the potential lifestyle-related risk factors of CP/CPPS and its pain severity in Chinese population. METHODS: Participants were recruited from seven hospitals in Shanghai from July 2012 to August 2013. Demographics, medical history, diet and lifestyle information, and CP/CPPS symptoms were obtained from each participant using a questionnaire. Univariate and multivariate logistic regression analyses were used to identify potential lifestyle-related risk factors for CP/CPPS and its pain severity. RESULTS: A total of 784 men with CP/CPPS and 785 controls were enrolled in this study. Multivariate regression model indicated that age, nightshift work, stress, smoking status, alcohol consumption, less water intake, imbalanced diet, frequent sexual activity, delaying ejaculation and holding urine were identified as potential risk factors for CP/CPPS, whereas sedentary lifestyle, caffeinated drinks and less water intake were associated with severe pain in CP/CPPS patients. CONCLUSIONS: Several diet and lifestyle factors associated with CP/CPPS and pain severity were determined in this study. These modifiable conditions are potential targets for treatment of CP/CPPS. However, further studies are necessary to determine their role in the pathogenesis of CP/CPPS. PMID- 26666412 TI - Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies. AB - OBJECTIVE: Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. METHODS: A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. RESULTS: Ten eligible studies were included to investigate the association between Epstein-Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53-13.00, P<0.001). The association between human cytomegalovirus (HCMV) and chronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41-9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95-8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21-4.86). CONCLUSION: The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV and HCMV, are significantly associated with chronic periodontitis. There is insufficient evidence to support associations between HSV, HHV-7 and chronic periodontitis. PMID- 26666413 TI - Feasibility of using self-reported patient data in a national diabetes register. AB - BACKGROUND: In order to improve recruitment of patients to the Norwegian diabetes register for adults, a questionnaire was designed to collect data directly from patients. The main aim of this study was to assess the agreement of questionnaire data with data reported to the Register from health care personnel during routine consultations. METHODS: Patient data were obtained by sending a questionnaire with 27 of the 41 Register variables to 3714 members of the Norwegian Diabetes Association. Questionnaire data were compared with data already in the Register. Paired t-tests, percentages of total agreement, percentages of "positive" answers and kappa coefficients (k) were used for comparing data. RESULTS: Of the 1645 replies (44.3 %), the Register already had data on 324 patients for comparison. Response rate for most variables was better from patients (ranging from 76-100 %) compared with health care professionals (33-100 %). For 17 of 25 assessable variables including diabetes duration, height, weight, HbA1c, drug treatment and several diabetes complications, agreement was substantial or better with kappa >0.60. Data on family history of premature heart disease (k-0.59), foot examination (k = 0.26), foot ulcer (k = 0.32) and arterial surgery (k = 0.24) seemed to be difficult to answer by patients, whereas data on physical activity and self-monitoring of glucose seemed to be better when reported by patients. CONCLUSIONS: Patient response rate was acceptable, and data had good concordance with data from health care professionals for most variables. However, registers using patient questionnaires should compare questionnaire data with data from professionals at regular intervals. PMID- 26666414 TI - Genomic and transcriptomic analyses of the Chinese Maotai-flavored liquor yeast MT1 revealed its unique multi-carbon co-utilization. AB - BACKGROUND: Revealing genetic mechanisms behind specific physiological characteristics of Saccharomyces cerevisiae from specific environments is important for industrial applications and requires precise understanding. RESULTS: Maotai strain MT1 was isolated from the complicated Chinese Maotai flavored liquor-making environment with extremely high temperatures, and acidic and ethanol stresses. Compared with the type strain S288c, MT1 can tolerate high acidity (pH 2.0), high ethanol levels (16 %) and high temperatures (44 degrees C). In addition, MT1 can simultaneously utilize various sugars, including glucose, sucrose, galactose, maltose, melibiose, trehalose, raffinose and turanose. Genomic comparisons identified a distinct MT1 genome, 0.5 Mb smaller than that of S288c. There are 145 MT1-specific genes that are not in S288c, including MEL1, MAL63, KHR1, BIO1 and BIO6. A transcriptional comparison indicated that HXT5 and HXT13, which are theoretically repressed by glucose, were no longer inhibited in MT1 and were highly expressed even in a medium containing 70 g/L glucose. Thus, other sugars may be co-utilized with glucose by MT1 without diauxic growth. CONCLUSIONS: Based on a functional genomics analysis, we revealed the genetic basis and evolutionary mechanisms underlying the traits of the Chinese Maotai-flavored yeast MT1. This work provides new insights for the genetic breeding of yeast and also enriches the genetic resources of yeast. PMID- 26666415 TI - Thyroid function testing in women who had a stillbirth. AB - CONTEXT: Thyroid dysfunction is thought to be associated with stillbirth. Therefore, thyroid function is often recommended in the diagnostic investigations for stillbirth. OBJECTIVE: We aimed to evaluate the added value of thyroid function testing in the diagnostic investigations for stillbirth. DESIGN AND PATIENTS: A nationwide multicentre prospective cohort study in 1025 women who suffered stillbirth >20 weeks of gestation performed between 2002 and 2008. In each woman, an extensive diagnostic work-up was performed, including placental examination and autopsy. TSH and FT4 values below the 2.5th percentile or above the 97.5th percentile according local laboratory reference values were regarded as abnormal. Women with a history of thyroid disease were evaluated separately. MAIN OUTCOME MEASURES: Thyroid function abnormalities in women with stillbirth. RESULTS: Of 1025 included women, 21 had a history of thyroid disease (2%). In the 875 with TSH and FT4 results and no history of thyroid disease, 10% had hypothyroxinemia, 4.6% subclinical hypothyroidism, 1.6% overt hypothyroidism and 1.5% subclinical hyperthyroidism. Women with a subclinical hyperthyroidism more often had a foetal death caused by foetal hydrops: 23% vs 2.9% (adjusted OR 10.3, 95% CI 2.5-42). CONCLUSIONS: Women with a stillbirth had a slightly higher prevalence of overt hypothyroidism, subclinical hypothyroidism and hypothyroxinaemia compared to previous studies on thyroid dysfunction in pregnant women. Given the absence of a strong associations with the cause of stillbirth, and no demonstrated beneficial effects of treating thyroid dysfunction in these women, routine screening after stillbirth is not justified. PMID- 26666416 TI - British GPs keep going for longer: is the 12 second interruption history? PMID- 26666417 TI - Lusutrombopag: First Global Approval. AB - Lusutrombopag (Mulpleta(r)) is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist being developed by Shionogi for chronic liver disease (CLD) patients with thrombocytopenia prior to elective invasive surgery. Lusutrombopag acts selectively on the human TPO receptor and activates signal transduction pathways that promote the proliferation and differentiation of bone marrow cells into megakaryocytes, thereby increasing platelet levels. In September 2015, lusutrombopag received its first global approval in Japan for the improvement of CLD-associated thrombocytopenia in patients scheduled to undergo elective invasive procedures. This article summarizes the milestones in the development of lusutrombopag leading to this first approval. PMID- 26666418 TI - Capsaicin 8 % Patch: A Review in Peripheral Neuropathic Pain. AB - The capsaicin 8 % patch (QUTENZA(r)) is an adhesive patch containing a high concentration (8 % w/w) of synthetic capsaicin, a selective agonist of transient receptor potential vanilloid 1 channel. It is approved for treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain in the EU; it is only approved to treat postherpetic neuralgia (PHN) in the USA. In patients with painful diabetic peripheral neuropathy (PDPN), a single 30-min application of the capsaicin 8 % patch significantly improved pain relief and sleep quality compared with placebo in a 12-week double-blind trial. In a 52-week, randomized trial, up to seven consecutive 30-min treatments with the capsaicin 8 % patch (<=7 treatments each at least 8 weeks apart) plus standard of care therapy was associated with sustained pain relief and no negative neurological safety consequences compared with standard of care. In two randomized trials, a single 60-min application of the capsaicin 8 % patch reduced pain scores significantly more than a low concentration (0.04 %) capsaicin control patch in patients with PHN. Capsaicin 8 % patch treatment was noninferior to pregabalin (optimized dosage) in a randomized trial in patients with nondiabetic peripheral neuropathic pain. Results in two trials in patients with HIV-AN were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8 % patch was associated with expected, transient, capsaicin-related application-site adverse events such as erythema and pain. PMID- 26666419 TI - The personal value of being part of a Tropical Health Education Trust (THET) links programme to develop a palliative care degree programme in Sub Saharan Africa: a descriptive study of the views of volunteer UK health care professionals. AB - BACKGROUND: There is a global need to expand palliative care services to reach the increasing number requiring end of life care. In developing countries where the incidences of cancer are rising there is an urgent need to develop the palliative care workforce. This paper reports on a UK Department for international development (DFID) initiative funded through the Tropical Health Education Trust (THET) where palliative care staff, both clinical and academic, volunteered to help to develop, support and deliver a degree in palliative care in sub-Saharan Africa. The objective of the study was to explore the personal impact on the health care professionals of being part of this initiative. METHODS: An evaluation approach using a confidential electronic survey containing quantitative and qualitative questions was distributed to all 17 volunteers on the programme, three months after completion of the first cohort. Data were analysed using descriptive statistics and content thematic analysis. Ethical review deemed the study to be service evaluation. RESULTS: 82 % (14) responded and several themes emerged from the data including the positive impact on teaching and educational skills; clinical practice and finally personal development. Using a score of 1-10 (1-no impact, 10 maximum impact) 'Lifestyle choices - life work balance' (rating 7.83) had the most impact. CONCLUSIONS: This approach to supporting the development of palliative care in Sub-Saharan Africa through skill sharing in supporting the delivery of a degree programme in palliative care was successful in terms of delivery of the degree programme, material development and mentorship of local staff. Additionally, this study shows it provided a range of positive impacts on the volunteer health care professionals from the UK. Professional impacts including increased management skills, and being better prepared to undertake a senior role. However it is the personal impact including lifestyle choices which the volunteers reported as the highest impact. Interestingly, several of the faculty have joined other volunteer programmes to continue to support the international development of palliative care. PMID- 26666420 TI - Is the Glass Half Full or Half Empty? PMID- 26666421 TI - Spatio-temporal genetic heterogeneity of CTNNB1 mutations in sporadic desmoid type fibromatosis lesions. AB - Desmoid type fibromatosis (DT) is a rare lesion of unclear pathogenesis that most often presents a mutation of the (beta-catenin) gene. The natural history and clinical evolution are highly variable between patients and to date there is no consensus on optimal therapy. We report two cases of a patient with multiple DT lesions. Molecular investigations performed in both patients on multiple tumors at different anatomical sites revealed non-identical CTNNB1 mutations. The first patient was a 39-year-old man with a history of recurrent DT. In two of the DT lesions, three different mutations were found in codons 41 and 45, respectively. The lesions showed marked inflammatory features, characterized by IgG4 positive lymphoplasmacytic infiltrates and a foreign body reaction, which increased in intensity over time. The patient was eventually treated with a COX-2 inhibitor and the remaining mass was stabilized. In the two DT lesions of the second patient, CTNNB1 mutations S45P and T41A were found. The presence of different mutations in multiple focally recurrent sporadic DT lesions indicates that they do not have a clonal relationship. Our data suggest that a CTNNB1 mutation is a necessary event probably by providing a selective growth advantage. An IgG4 host antigen response is discussed as a potential predisposing factor for one of the patients. PMID- 26666422 TI - Absence of Benefit of Transcatheter Arterial Chemoembolization (TACE) in Patients with Resectable Solitary Hepatocellular Carcinoma. AB - BACKGROUND: This study aimed to assess the prognostic impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival outcomes in patients undergoing resection of small solitary hepatocellular carcinoma (HCC). METHODS: Enrolled patients had undergone macroscopic curative resection of solitary 2-5 cm HCC with (n = 105) or without (n = 830; control group) preoperative TACE. RESULTS: TACE group was divided into subgroups A (n = 68, 1-2 TACEs within 12 months), B (n = 23, >= 3 TACEs within 12 months), and C (n = 14, TACE prior to 12 months). The number of TACE sessions was 1.8 +/- 1.6. In TACE A C subgroups, pathological response of tumor necrosis >50 % at median post-TACE period after final TACE was observed in 41 (60.3 %) at 1.9 months, 10 (43.5 %) at 2.1 months, and 2 (14.3 %) at 18.9 months, respectively. The 5-year tumor recurrence and patient survival rates were 62.8 and 70.4 % in TACE group and 51.4 and 83.4 % in control group, respectively (p <= 0.003). Median periods of postoperative tumor recurrence in TACE A-C subgroups and control group were 35, 13, 14, and 55 months, respectively (p < 0.001); and postoperative survival periods at 75 % survival rate were 51, 38, 51, and 98 months, respectively (p = 0.003). TACE-induced extensive tumor necrosis did not improve postoperative prognosis in TACE A subgroup (p >= 0.053). Postoperative prognosis after preoperative sequential TACE and portal vein embolization was comparable to that of the control group (p >= 0.052). CONCLUSIONS: Preoperative TACE for small solitary HCCs may adversely affect post-resection prognosis, irrespective of pathological responses. Preoperative TACE should be avoided for patients with resectable small HCCs. PMID- 26666424 TI - Rejection of rejection: a novel approach to overcoming barriers to publication. PMID- 26666423 TI - Implementation of Enhanced Recovery (ERAS) in Colorectal Surgery Has a Positive Impact on Non-ERAS Liver Surgery Patients. AB - BACKGROUND: Enhanced recovery after surgery (ERAS) reduces complications and hospital stay in colorectal surgery. Thereafter, ERAS principles were extended to liver surgery. Previous implementation of an ERAS program in colorectal surgery may influence patients undergoing liver surgery in a non-ERAS setting, on the same ward. This study aimed to test this hypothesis. METHODS: Retrospective analysis based on prospective data of the adherence to the institutional ERAS liver protocol (compliance) in three cohorts of consecutive patients undergoing elective liver surgery, between June 2010 and July 2014: before any ERAS implementation (pre-ERAS n = 50), after implementation of ERAS in colorectal (intermediate n = 50), and after implementation of ERAS in liver surgery (ERAS liver n = 74). Outcomes were functional recovery, postoperative complications, hospital stay, and readmissions. RESULTS: The three groups were comparable for demographics; laparoscopy was more frequent in ERAS-liver (p = 0.009). Compliance with the enhanced recovery protocol increased along the three periods (pre-ERAS, intermediate, and ERAS-liver), regardless of the perioperative phase (pre-, intra , or postoperative). ERAS-liver group displayed the highest overall compliance rate with 73.8 %, compared to 39.9 and 57.4 % for pre-ERAS and intermediate groups (p = 0.072/0.056). Overall complications were unchanged (p = 0.185), whereas intermediate and ERAS-liver groups showed decreased major complications (p = 0.034). Consistently, hospital stay was reduced by 2 days (p = 0.005) without increased readmissions (p = 0.158). CONCLUSIONS: The previous implementation of an ERAS protocol in colorectal surgery may induce a positive impact on patients undergoing non-ERAS-liver surgery on the same ward. These results suggest that ERAS is safely applicable in liver surgery and associated with benefits. PMID- 26666425 TI - The Marikana Massacre: Why Heads Must Roll. AB - The massacre of thirty-four striking platinum miners on the 16 August 2012 near the village of Marikana in South Africa revealed the collusion of the state, mining capital, and sections of the labor movement. Analysis of the buildup to the killings highlight the way the mining industry systematically ignored evidence of the potential for social conflict as a result of its labor policies over many years. Further, the way in which the killings unfolded and were covered up are evidence that justice was denied to workers and their families. It should provide a sobering reminder of the power of elite alliances and the elite capture of seemingly democratic institutions within the labor movement, even in a post apartheid South Africa. PMID- 26666426 TI - Case of generalized eosinophilic pustular folliculitis induced by allopurinol. PMID- 26666427 TI - Efficacy of an Enrichment Media for Increasing Threshold for Carbapenem-Resistant Enterobacteriaceae Screening. AB - BACKGROUND: Identification of carbapenem-resistant Enterobacteriaceae (CRE) is complex and a major laboratory challenge; clinical cultures may diagnose only some of the CRE carriers among patients, thus it is crucial to perform asymptomatic carriage screening. MATERIALS AND METHODS: We compare the efficacy of a rectal sample culture prior to enrichment with BHI (Brain Heart Infusion) Broth and following 18-24 h. All rectal samples were applied on CHROMagar KPC selective growth media and then seeded on MacConkey agar selective growth media with an applied disk of Imipenem antibiotic on top of the media, then inserted into enrichment BHI Broth. After 18-24 h incubation with enrichment media, all samples were applied again on this media. RESULTS: From the 2,245 rectal samples, CRE colonies were found in 96 (4.3%). Following enrichment with BHI Broth, CRE colonies were found in 111 (4.9%) CHROMagar KPC plates and 106 (4.7%) MacConkey agar. CONCLUSION: We were able to demonstrate that the number of CRE-positive results increased due to use of additional enrichment with BHI Broth. Therefore, we recommend applying this method of addition of liquid enrichment media as part of a culture protocol routine for CRE screening. PMID- 26666428 TI - Associations between lifetime tobacco exposure with infertility and age at natural menopause: the Women's Health Initiative Observational Study. AB - BACKGROUND: Several studies have investigated the association of tobacco use with infertility and age at natural menopause, yet few have explored secondhand smoke (SHS) exposure with these outcomes. This study offers a comprehensive, quantified secondary data analysis of these issues using the Women's Health Initiative Observational Study (WHI OS). PURPOSE: This study examines associations between lifetime tobacco exposure-active smoking and SHS-and infertility and natural menopause (before age 50). METHODS: Information on smoking, lifetime fertility status, and age at natural menopause was collected and available from 93 676 postmenopausal women aged 50-79 enrolled in the WHI OS from 1993 to 1998 at 40 centres in the USA. Multivariate-adjusted regression models were used to estimate ORs and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. RESULTS: Overall, 15.4% of the 88 732 women included in the analysis on infertility met criteria for the condition. 45% of the 79 690 women included in the analysis on natural menopause (before age 50) met criteria for the condition. Active-ever smokers had overall OR's of 1.14 (95% CI 1.03 to 1.26) for infertility, and 1.26 (95% CI 1.16 to 1.35) for earlier menopause than never-smoking women. Never-smoking women with the highest levels of lifetime SHS exposure had adjusted OR's of 1.18 (95% CI 1.02 to 1.35) for infertility, and 1.18 (95% CI 1.06 to 1.31) for earlier menopause. Active-ever smokers reached menopause 21.7 months earlier than the mean of 49.4 years for never-smokers not exposed to SHS, and women exposed to the highest level of SHS reached menopause 13.0 months earlier. CONCLUSIONS: Active smoking and SHS exposure are associated with increased risk of infertility and natural menopause occurring before the age of 50 years. PMID- 26666429 TI - Purification and characterization of a novel chitinase from Trichosanthes dioica seed with antifungal activity. AB - Chitinases are a group of enzymes that show differences in their molecular structure, substrate specificity, and catalytic mechanism and widely found in organisms like bacteria, yeasts, fungi, arthropods actinomycetes, plants and humans. A novel chitinase enzyme (designated as TDSC) was purified from Trichosanthes dioica seed with a molecular mass of 39+/-1 kDa in the presence and absence of beta-mercaptoethanol. The enzyme was a glycoprotein in nature containing 8% neutral sugar. The N-terminal sequence was determined to be EINGGGA which did not match with other proteins. Amino acid analysis performed by LC-MS revealed that the protein was rich in leucine. The enzyme was stable at a wide range of pH (5.0-11.0) and temperature (30-90 degrees C). Chitinase activity was little bit inhibited in the presence of chelating agent EDTA (ethylenediaminetetraaceticacid), urea and Ca(2+). A strong fluorescence quenching effect was found when dithiothreitol and sodium dodecyl sulfate were added to the enzyme. TDSC showed antifungal activity against Aspergillus niger and Trichoderma sp. as tested by MTT assay and disc diffusion method. PMID- 26666430 TI - Heparin based polyurethanes: A state-of-the-art review. AB - Polyurethanes (PUs) are considered currently as one of the established bio compatible and blood compatible biomaterials offering tremendous structure property relationship. But few limitations such as low resistance to micro-emboli and thrombi are still associated with these biomaterials that restricted their applications and hence need to be modified. Heparin, a highly sulfonated and negatively charged member of glycosaminoglycan family is well established for their anti-thrombin, anticoagulant and many biological activities that make it a highly attractive candidate capable of modifying or tailoring polymer properties. Incorporation of heparin for the improvement of biocompatibility of PUs is an interesting approach and enabling emerging technology. This review focuses on the methods used for modification of PUs via heparin with their pros and cons. The major PU-heparin systems with the recent developments and their possible biomedical applications are discussed. PMID- 26666431 TI - Impact of three phthalate esters on the sexual reproduction of the Monogonont rotifer, Brachionus calyciflorus. AB - Phthalate esters are widespread contaminants that can cause endocrine disruption in vertebrates. Studies showed that molecules with hormonal activities in vertebrates and invertebrates can affect asexual and sexual reproduction in rotifers. We investigated the impact of di-hexylethyl phthalate (DEHP), di-butyl phthalate (DBP) and butylbenzyl phthalate (BBP), on the asexual and sexual reproduction of the freshwater monogonont rotifer Brachionus calyciflorus in order to determine a potential environmental risk for sexual reproduction. We observed that DEHP has no significant impact on both asexual and sexual reproduction up to 2 mg/L. DBP has a positive effect on asexual reproduction at concentrations from 0.05 to 1 mg/L, but depresses it at 2 mg/L. Sexual reproduction is only affected at 2 mg/L and the impact observed is negative. BBP displayed a negative impact on both asexual and sexual reproduction at 1 and 2 mg/L. However we showed that the impacts of BBP on mixis and fertilization rates observed are due to the decrease in population growth rates at these concentrations and not to a direct impact of BBP on the mixis and the fertilization processes. Our results show that sexual reproduction in B. calyciflorus is not more sensitive than asexual reproduction to any of the substances tested which indicates the mode of action of these molecules is related to general toxicity and not to an interference with potential endocrine regulation of sexual reproduction. Comparison of effect concentrations and surface water contamination by phthalate esters suggests these compounds do not constitute a risk for primary consumers in these environments. PMID- 26666432 TI - House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes. AB - House dust mite (HDM) is an essential allergen in allergic diseases such as allergic rhinitis and asthma. The pathogenic mechanism of allergy is associated with cytokine release of lymphocytes and constitutive apoptosis of neutrophils. In this study, we examined whether HDM induces cytokine release of lymphocytes and whether the secretion of cytokines is involved in modulation of neutrophil apoptosis. In normal and allergic subjects, extract of Dermatophagoides pteronyssinus (DP) increased IL-6, IL-8, MCP-1, and GM-CSF secretion in a time dependent manner. This secretion was suppressed by PAR2i, an inhibitor of PAR2, in a dose-dependent manner, as well as by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of ERK, and BAY-11-7085, and an inhibitor of NF-kappaB. DP induced ERK and NF-kappaB activation in a time dependent manner. ERK activation was suppressed by PAR2i, LY294002, and AKTi, and NF-kappaB activation was blocked by PAR2i, LY294002, AKTi, and PD98059. Supernatants collected from normal and allergic neutrophils after DP treatment inhibited the apoptosis of normal and allergic neutrophils through suppression of caspase 9 and caspase 3 cleavage. DP inhibited neutrophil apoptosis in coculture of normal neutrophils with normal lymphocytes, similar to the anti-apoptotic effects of DP on neutrophils alone. DP more strongly inhibited apoptosis of allergic neutrophils cocultured with allergic lymphocytes than allergic neutrophils without lymphocytes. In summary, DP induces the release of cytokines through the PAR2/PI3K/Akt/ERK/NF-kappaB pathway, which has anti-apoptotic effects on neutrophils of normal and allergic subjects. These results will facilitate elucidation of the pathogenic mechanism of allergic diseases. PMID- 26666434 TI - Impacts of forestry planting on primary production in upland lakes from north west Ireland. AB - Planted forests are increasing in many upland regions worldwide, but knowledge about their potential effects on algal communities of catchment lakes is relatively unknown. Here, the effects of afforestation were investigated using palaeolimnology at six upland lake sites in the north-west of Ireland subject to different extents of forest plantation cover (4-64% of catchment area). (210)Pb dated sediment cores were analysed for carotenoid pigments from algae, stable isotopes of bulk carbon (delta(13)C) and nitrogen (delta(15)N), and C/N ratios. In lakes with >50% of their catchment area covered by plantations, there were two to sixfold increases in pigments from cryptophytes (alloxanthin) and significant but lower increases (39-116%) in those from colonial cyanobacteria (canthaxanthin), but no response from biomarkers of total algal abundance (beta carotene). In contrast, lakes in catchments with <20% afforestation exhibited no consistent response to forestry practices, although all lakes exhibited fluctuations in pigments and geochemical variables due to peat cutting and upland grazing prior to forest plantation. Taken together, patterns suggest that increases in cyanobacteria and cryptophyte abundance reflect a combination of mineral and nutrient enrichment associated with forest fertilization and organic matter influx which may have facilitated growth of mixotrophic taxa. This study demonstrates that planted forests can alter the abundance and community structure of algae in upland humic lakes of Ireland and Northern Ireland, despite long histories of prior catchment disturbance. PMID- 26666435 TI - Fgf3-Fgf4-cis: A new mouse line for studying Fgf functions during mouse development. AB - The fibroblast growth factor (FGF) family consists of 22 ligands in mice and humans. FGF signaling is vital for embryogenesis and, when dysregulated, can cause disease. Loss-of-function genetic analysis in the mouse has been crucial for understanding FGF function. Such analysis has revealed that multiple Fgfs sometimes function redundantly. Exploring such redundancy between Fgf3 and Fgf4 is currently impossible because both genes are located on chromosome 7, about 18.5 kb apart, making the frequency of interallelic cross-over between existing mutant alleles too infrequent to be practicable. Therefore, we retargeted Fgf3 and Fgf4 in cis, generating an Fgf3 null allele and a conditional Fgf4 allele, subject to Cre inactivation. To increase the frequency of cis targeting, we used an F1 embryonic stem cell line that contained 129/SvJae (129) and C57BL/6J (B6) chromosomes and targeting constructs isogenic to the 129 chromosome. We confirmed cis targeting by assaying for B6/129 allele-specific single-nucleotide polymorphisms. We demonstrated the utility of the Fgf3(Delta)-Fgf4(flox)-cis mouse line by showing that the caudal axis extension defects found in the Fgf3 mutants worsen when Fgf4 is also inactivated. This Fgf3(Delta)-Fgf4(flox)-cis line will be useful to study redundancy of these genes in a variety of tissues and stages in development. PMID- 26666433 TI - Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study. AB - Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R-B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12-71 months). Toxicity was moderate, mainly grades 1 and 2. R-B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs. PMID- 26666436 TI - Complementary and Alternative Medicines: Usage and Its Determinant Factors Among Outpatients in Southeast of Iran. AB - Prevalence of complementary and alternative medicines is increasing specially in patients with chronic diseases. Therefore, based on the high prevalence of chronic disorders, the present study aimed to determine complementary and alternative medicine usage frequency and its determinant factors. This was a cross-sectional study. Five hundred clients participated in the study by using convenience sampling. A 2-part questionnaire (including demographic form and researcher-created questionnaire) was used for studying the prevalence of using complementary and alternative medicine methods, and users' satisfaction. Findings showed that 75.4% of people used at least one complementary and alternative medicine method. Most of users consumed medicinal plants (69.4%). The most common reason of using a complementary and alternative medicine method was common cold (32.9%). The highest satisfaction belonged to massage (2.94 +/- 0.74). The usage of complementary and alternative medicine was 3.22 times higher in people with academic educations when compared with illiterate people. Concerning the high usage of complementary and alternative medicine, it is necessary to train specialists in this field in order to offer such treatments in a safe manner. Also, outcomes of application of complementary and alternative medicine methods should be studied. PMID- 26666437 TI - Palliative radiotherapy for Japanese patients with malignant melanoma: a single institution experience. AB - PURPOSE: This study aimed to clarify the significance of palliative radiotherapy for Japanese patients with malignant melanoma based on the experience of our institution. MATERIALS AND METHODS: Twenty-nine patients with malignant melanoma who underwent palliative radiotherapy at our facility were included in the investigation. Median radiation dose was 30 Gy (4-30). RESULTS: Median follow-up time was 4.2 months (range 2.7-40.5 months). Twenty-two patient (75.9%) died during the follow-up. The response rate of overall symptoms to radiotherapy was 63.0%. The rate of completely resolved hemorrhage was relatively high (81.8%). The median time of freedom from progression in completely resolved symptoms was 3.1 months (range 0.2-27.8 months). Radiation dose <30 Gy and poor performance status tended to be associated with poor symptomatic relief in treatment site (p = .080 and p = .068, respectively). There were very few severe toxic events. CONCLUSION: Two thirds of symptoms were safely alleviated by palliative radiotherapy for Japanese patients with malignant melanoma. The therapeutic effect was retained for a substantial duration. Further domestic studies are warranted. PMID- 26666438 TI - Innovation in medicine: Ignaz the reviled and Egas the regaled. AB - In our current climate of rapid technological progress, it seems counterintuitive to think that modern science can learn anything of ethical value from the dark recesses of the nineteenth century or earlier. However, this happens to be quite true, with plenty of knowledge and wisdom to be gleaned by studying our scientific predecessors. Presently, our journals are flooded with original concepts and potential breakthroughs, a continuous stream of ideas pushing the frontiers of knowledge ever forward. Some ideas flourish while others flounder; but what sets the two apart? The distinguishing feature between success and failure within this context is the ability to discern the appropriate time to accept an innovation with open arms, versus when to take a more cautious approach. And the primary arbiters for whether an idea will catch on or not are the professional audience. I illustrate this concept by comparing the initial reception of two innovative ideas from Medicine's past: sterile technique, and prefrontal lobotomy. Sterile technique was first introduced by Dr. Ignaz Semmelweis and was initially ridiculed and rejected, with Semmelweis eventually dying in exile. Conversely, lobotomy was accepted and lauded and its inventor, Dr. Egas Moniz, won the Nobel Prize for his "discovery". This begs the question: why was a technique with the potential to save millions of lives initially rejected, whereas paradoxically, one that compromised and sometimes destroyed lives, accepted? Here I explore and analyze the potential reasons why, suggest how we can learn from these mistakes of the past and apply new insight to some current ethical dilemmas. PMID- 26666439 TI - High-yield production of canine parvovirus virus-like particles in a baculovirus expression system. AB - An optimized VP2 gene from the current prevalent CPV strain (new CPV-2a) in China was expressed in a baculovirus expression system. It was found that the VP2 proteins assembled into virus-like particles (VLPs) with antigenic properties similar to those of natural CPV and with an especially high hemagglutination (HA) titer (1:2(20)). Dogs intramuscularly or orally immunized with VLPs produced antibodies against CPV with >1:80 hemagglutination inhibition (HI) units for at least 3 months. The CPV VLPs could be considered for use as a vaccine against CPV or as a platform for research on chimeric VLP vaccines against other diseases. PMID- 26666440 TI - Grapevine Pinot gris virus seems to have recently been introduced to vineyards in Veneto, Italy. AB - Grapevine Pinot gris virus (GPGV), a member of the genus Trichovirus in the family Betaflexiviridae, was recently discovered in Italy and subsequently in other European countries and in Korea. In this study, we assessed the occurrence of GPGV in 441 samples from Western and Eastern Europe collected over the period 2002-2014. The results suggest that the virus had recently appeared in the Veneto region (Northeast Italy) and had been present in some Eastern European countries for at least 10 years. The molecular characterization of the 5'-terminal genomic region of several GPGV isolates from Italy and other European countries showed low polymorphism, with a maximum nucleotide sequence divergence of 3.2%. PMID- 26666441 TI - Complete genomic sequence of barley (Hordeum vulgare) endornavirus (HvEV) determined by next-generation sequencing. AB - Endornaviruses are unusual plant-, fungus- and oomycete-infecting viruses with a large, ca 14- to 17-kb linear double-stranded RNA (dsRNA) genome and a persistent lifestyle. The complete genome sequence of an endornavirus from the barley (Hordeum vulgare) Nerz variety was determined from paired Illumina MySeq reads derived from purified dsRNAs. The genome is 14,243 nt long, with 5' and 3' non coding regions of 207 and 47 nt, respectively. It encodes a single large protein of 4663 amino acids that carries conserved motifs for a methyltransferase, a helicase and an RNA-dependent RNA polymerase. The sequence of Hordeum vulgare endornavirus (HvEV) carries all the hallmarks of a typical member of the genus Endornavirus, with the exception of an UDP-glycosyltransferase motif observed in many, but not all, endornaviral genomes. PMID- 26666442 TI - Giant viruses of the Kutch Desert. AB - The Kutch Desert (Great Rann of Kutch, Gujarat, India) is a unique ecosystem: in the larger part of the year it is a hot, salty desert that is flooded regularly in the Indian monsoon season. In the dry season, the crystallized salt deposits form the "white desert" in large regions. The first metagenomic analysis of the soil samples of Kutch was published in 2013, and the data were deposited in the NCBI Sequence Read Archive. At the same time, the sequences were analyzed phylogenetically for prokaryotes, especially for bacteria. In the present work, we identified DNA sequences of recently discovered giant viruses in the soil samples from the Kutch Desert. Since most giant viruses have been discovered in biofilms in industrial cooling towers, ocean water, and freshwater ponds, we were surprised to find their DNA sequences in soil samples from a seasonally very hot and arid, salty environment. PMID- 26666443 TI - [Optimal timing of parathyroidectomy after renal transplantation]. PMID- 26666444 TI - Selective inhibition of PTEN preserves ischaemic post-conditioning cardioprotection in STZ-induced Type 1 diabetic rats: role of the PI3K/Akt and JAK2/STAT3 pathways. AB - Patients with diabetes are vulnerable to MI/R (myocardial ischaemia/reperfusion) injury, but are not responsive to IPostC (ischaemic post-conditioning) which activates PI3K (phosphoinositide 3-kinase)/Akt (also known as PKB or protein kinase B) and JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathways to confer cardioprotection. We hypothesized that increased cardiac PTEN (phosphatase and tensin homologue deleted on chromosome 10), a major negative regulator of PI3K/Akt, is responsible for the loss of diabetic heart sensitivity to IPostC cardioprotecton. In STZ (streptozotocin) induced Type 1 diabetic rats subjected to MI/R (30 min coronary occlusion and 120 min reperfusion), the post-ischaemic myocardial infarct size, CK-MB (creatine kinase-MB) and 15-F2t-isoprostane release, as well as cardiac PTEN expression were significantly higher than those in non-diabetic controls, concomitant with more severe cardiac dysfunction and lower cardiac Akt, STAT3 and GSK-3beta (glycogen synthase kinase 3beta) phosphorylation. IPostC significantly attenuated post-ischaemic infarct size, decreased PTEN expression and further increased Akt, STAT3 and GSK-3beta phosphorylation in non-diabetic, but not in diabetic rats. Application of the PTEN inhibitor BpV (bisperoxovanadium) (1.0 mg/kg) restored IPostC cardioprotection in diabetic rats. HPostC (hypoxic post-conditioning) in combination with PTEN gene knockdown, but not HPostC alone, significantly reduced H/R (hypoxia/reoxygenation) injury in cardiac H9c2 cells exposed to high glucose as was evident from reduced apoptotic cell death and JC-1 monomer in cells, accompanied by increased phosphorylation of Akt, STAT3 and GSK-3beta. PTEN inhibition/gene knockdown mediated restoration of IPostC/HPostC cardioprotection was completely reversed by the PI3K inhibitor wortmannin, and partially reversed by the JAK2 inhibitor AG490. Increased cardiac PTEN, by impairing PI3K/Akt and JAK2/STAT3 pathways, is a major mechanism that rendered diabetic hearts not responsive to post-conditioning cardioprotection. PMID- 26666445 TI - Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study. AB - Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (beta=19.9 MUm/kg, 95%CI 11.1, 28.6; P<0.001) and birth skinfold thickness (beta=6.9 MUm/mm, 95%CI 3.3, 10.5; P<0.001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (beta=11.3 MUm/kg increase, 95%CI 2.2, 20.3; P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk. PMID- 26666447 TI - Biometrics' new identity--measuring more physical and biological traits: Research into the characteristics that are unique to an individual is addressing the need to correctly identify people in a variety of medical, social and security contexts. PMID- 26666448 TI - Improving pediatric asthma care: A partnership between pediatric primary care clinics and a free-standing Children's Hospital. AB - BACKGROUND: Asthma is a common chronic disease of childhood. Providers' adherence to asthma guidelines is still less than optimal. OBJECTIVES: To determine if an Asthma Education Program aimed at primary care practices can improve asthma care within practices and if the results vary by duration of the program. METHODS: Ten practices were randomly assigned to an Early Asthma Education Intervention (EI) group or a Delayed Asthma Education Intervention (DI) group. The EI group received the intervention for 12 months and was monitored for 6 additional months. The DI group was observed without intervention for 12 months, then received the intervention for 6 months, and was monitored for 6 additional months. The program included training of asthma educators in each practice and then monitoring for improvement in medical record documentation of National Asthma Education and Prevention Program (NAEPP) asthma quality indicators by blinded random review of patient charts. RESULTS: In the EI group, 6-, 12-, and 18-month data revealed significant improvement in documentation of asthma severity, education, action plan, night time symptoms, and symptoms with exercise compared to baseline and compared to DI group at baseline and at the 12-month interval. In the DI group, significant improvement in documentation in all of the above endpoints and also in documentation of NAEPP treatment guidelines was noted at 18 and 24 months. In both groups, documentation levels remained relatively stable at 6 months after the intervention, with no significant differences between groups. While improved, guideline adherence was <80% for half of the indicators. CONCLUSION: In-office training of non-physician asthma providers improves the quality of asthma care. PMID- 26666449 TI - Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction. AB - Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. Patients with acute middle cerebral artery infarction who had National Institute of Health Stroke Scale (NIHSS) score of at least 15 were included. Baseline characteristics and amount of fluid intake during the first few days were compared in patients with and without malignant brain edema. One hundred ninety-three patients were studied. Mean NIHSS score was 20. Malignant brain edema occurred in 69 patients (36%). Higher amount of fluid intake (>1650 ml or >28 ml/kg/day or >93% of daily maintenance fluid) showed a significant association with malignant brain edema (OR = 13.86, 95% CI 5.11-37.60, p value <0.001). Decompressive surgery was performed in 35 patients (18%). With mean follow-up of 12 months, 49 patients (49/184, 27%) had favorable outcomes (modified Rankin scale (mRS) 0-2) at final follow-up. Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema. PMID- 26666450 TI - Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response. AB - A major limiting factor retarding the clinical success of dendritic cell (DC) based genetic immunizations (DNA vaccination) is the scarcity of biologically safe and effective carrier systems for targeting the antigen-encoded DNA vaccines to DCs under in vivo settings. Herein, we report on a potent, mannose receptor selective in vivo DC-targeting liposomes of a novel cationic amphiphile with mannose-mimicking shikimoyl head-group. Flow cytometric experiments with cells isolated from draining lymph nodes of mice s.c. immunized with lipoplexes of pGFP plasmid (model DNA vaccine) using anti-CD11c antibody-labeled magnetic beads revealed in vivo DC-targeting properties of the presently described liposomal DNA vaccine carrier. Importantly, s.c. immunizations of mice with electrostatic complex of the in vivo DC-targeting liposome and melanoma antigen-encoded DNA vaccine (p-CMV-MART1) induced long-lasting antimelanoma immune response (100 days post melanoma tumor challenge) with remarkable memory response (more than 6 months after the second tumor challenge). The presently described direct in vivo DC-targeting liposomal DNA vaccine carrier is expected to find future exploitations toward designing effective vaccines for various infectious diseases and cancers. PMID- 26666451 TI - In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa. AB - Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (Rho(S334)) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-specific disruption of Rho(S334), which prevented retinal degeneration and improved visual function. PMID- 26666452 TI - Core Standards of the EUBIROD Project. Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery. AB - BACKGROUND: A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes. METHODS: Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality. RESULTS: While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus. CONCLUSIONS: The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe. PMID- 26666453 TI - A high performance hybrid battery based on aluminum anode and LiFePO4 cathode. AB - A novel hybrid battery utilizing an aluminum anode, a LiFePO4 cathode and an acidic ionic liquid electrolyte based on 1-ethyl-3-methylimidazolium chloride (EMImCl) and aluminum trichloride (AlCl3) (EMImCl-AlCl3, 1-1.1 in molar ratio) with or without LiAlCl4 is proposed. The hybrid ion battery delivers an initial high capacity of 160 mA h g(-1) at a current rate of C/5. It also shows good rate capability and cycling performance. PMID- 26666454 TI - Type I Diacylglycerol Acyltransferase (MtDGAT1) from Macadamia tetraphylla: Cloning, Characterization, and Impact of Its Heterologous Expression on Triacylglycerol Composition in Yeast. AB - Acyltransferase enzymes have been reported as useful biotechnological tools in order to increase oil yield and modify fatty acid composition. Macadamia species are able to accumulate unusually high levels of palmitoleic acid that besides oleic acid amounts to over 80% of monounsaturated fatty acids in the seed oil. In this work, a gene encoding a type 1 acyl-CoA:diacylglycerol acyltransferase (DGAT1) was cloned from M. tetraphylla. DGAT activity of the protein encoded by MtDGAT1 was confirmed by heterologous expression in a yeast mutant. Fatty acid composition of triacylglycerols synthesized by MtDGAT1 was compared to that of DGAT1 enzymes from Arabidopsis and Echium, with the results suggesting a substrate preference for monounsaturated over polyunsaturated fatty acids. Characteristics of MtDGAT1 may contribute to biochemical mechanisms determining the particular fatty acid composition of Macadamia oil and also indicate the possibility of using this enzyme in biotechnological approaches where a reduction of polyunsaturated fatty acids in the oil is desired. PMID- 26666455 TI - A high quality liquid-type quantum dot white light-emitting diode. AB - This study demonstrates a novel package design to store colloidal quantum dots in liquid format and integrate them with a standard LED. The high efficiency and high quality color performance at a neutral white correlated color temperature is demonstrated. The experimental results indicate that the liquid-type quantum dot white light-emitting diode (LQD WLED) is highly efficient and reliable. The luminous efficiency and color rendering index (CRI) of the LQD WLED can reach 271 lm Wop(-1) and 95, respectively. Moreover, a glass box is employed to prevent humidity and oxygen erosion. With this encapsulation design, our quantum dot box can survive over 1000 hours of storage time. PMID- 26666456 TI - Ototoxicity of acetic acid on the guinea pig cochlea. AB - BACKGROUND: To evaluate the ototoxicity of acetic acid solutions. METHODS: Compound action potentials (CAPs) of the eighth nerve were measured in guinea pigs before and after the application of acetic acid in the middle ear cavity. The pH values of the acetic acid solutions were pH 3.0, 4.0, and 5.0, and the application times were 30 min, 24 h, and 1 week. RESULTS: Acetic acid solution (pH 3.0, N = 3) for 30 min caused no significant elevation in CAP threshold at 4 kHz, but a significant elevation in the threshold was noted for 8 kHz and clicks. Acetic acid solutions (pH 4.0 N = 6, 5.0 N = 5) for 30 min caused no significant elevation in CAP. Acetic acid solution (pH 4.0) for 24 h (N = 5) caused significant elevations of the CAP threshold for 8 kHz, 4 kHz, and for clicks. Acetic acid (pH 5.0) for 24 h (N = 3) caused a significant elevation of the CAP threshold for 4 kHz, but not for 8 kHz or clicks. Acetic acid (pH 5.0) for 1 week (N = 3) caused a small but significant elevation CAP the threshold for 8 kHz and 4 kHz tone bursts, but no significant change was noted for clicks. CONCLUSIONS: We found a significant toxic effect of acetic acid in guinea pigs on eighth-nerve compound action potentials when the pH was 5.0 or lower. Clearly, the stronger the acidity, and longer the exposure time, the more the CAP threshold was elevated. PMID- 26666458 TI - New eudesmane-type sesquiterpenoids from the root bark of Pseudolarix kaempferi. AB - The phytochemical investigation of the root bark of Pseudolarix kaempferi yielded eight eudesmane-type sesquiterpenoids, including three new ones, 1alpha-hydroxyl 4(14)-en-beta-dihydroagarafuran (1), 1alpha, 2alpha-diacetoxy-8beta isobutanoyloxy-9alpha-benzoyl oxy-15-beta-(beta-furancarbonyloxy)-4beta, 6beta dihydroxy-beta-dihydroagarofuran (7), and 1alpha-acetoxy-2 alpha-furancarbonyloxy 8beta-isobutanoyloxy-9alpha-benzoyloxy-15beta-(beta-acetoxy)-4beta, 6beta dihydroxy-beta-dihydroagarofuran (8). Herein the new compounds 7 and 8 were reported as a mixture. The molecular structures of the isolated compounds were elucidated on the basis of extensive spectroscopic analysis, including UV, IR, NMR, and MS, and comparison with the literature data. PMID- 26666457 TI - Effects of postural specific sensorimotor training in patients with chronic low back pain: study protocol for randomised controlled trial. AB - BACKGROUND: Sensorimotor training (SMT) is popularly applied as a preventive or rehabilitative exercise method in various sports and rehabilitation settings. Yet, there is only low-quality evidence on its effect on pain and function. This randomised controlled trial will investigate the effects of a theory-based SMT in rehabilitation of chronic (>3 months) non-specific low back pain (CNLBP) patients. METHODS/DESIGN: A pilot study with a parallel, single-blinded, randomised controlled design. Twenty adult patients referred to the clinic for CNLBP treatment will be included, randomised, and allocated to one of two groups. Each group will receive 9 x 30 minutes of standard physiotherapy (PT) treatment. The experimental group will receive an added 15 minutes of SMT. For SMT, proprioceptive postural exercises are performed on a labile platform with adjustable oscillation to provoke training effects on different entry levels. The active comparator group will perform 15 minutes of added sub-effective low intensity endurance training. Outcomes are assessed on 4 time-points by a treatment blinded tester: eligibility assessment at baseline (BL) 2-4 days prior to intervention, pre-intervention assessment (T0), post-intervention assessment (T1), and at 4 weeks follow-up (FU). At BL, an additional healthy control group (n = 20) will be assessed to allow cross-sectional comparison with symptom-free participants. The main outcomes are self-reported pain (Visual Analogue Scale) and functional status (Oswestry Disability Index). For secondary analysis, postural control variables after an externally perturbed stance on a labile platform are analysed using a video-based marker tracking system and a pressure plate (sagittal joint-angle variability and centre of pressure confidence ellipse). Proprioception is measured as relative cervical joint repositioning error during a head-rotation task. Effect sizes and mixed-model MANOVA (2 groups * 4 measurements for 5 dependent variables) will be calculated. DISCUSSION: This is the first attempt to systematically investigate effects of a theory-based sensorimotor training in patients with CNLBP. It will provide analysis of several postural segments during a dynamic task for quantitative analysis of quality and change of the task performance in relation to changes in pain and functional status. TRIAL REGISTRATION: Trial registry number on cliniclatrials.gov is NCT02304120 , first registered on 17 November 2014. PMID- 26666459 TI - Management and outcomes in patients with Staphylococcus aureus bacteremia after implementation of mandatory infectious diseases consult: a before/after study. AB - BACKGROUND: Infectious disease (ID) consultations have been shown to increase adherence to guidelines and decrease mortality for patients with Staphylococcus aureus bacteremia (SAB). Here, we assessed the impact of a mandatory ID consultation policy for SAB. METHODS: We retrospectively reviewed all consecutive adult patients with SAB at two tertiary care teaching hospitals in Hamilton, ON, Canada. Mandatory ID consults for SAB were implemented on January 1(st) 2012. We compared SAB cases in 2011 (control group) with those in 2012 (intervention group). Outcomes included adherence to the Infectious Diseases Society of America guidelines and patient outcomes. RESULTS: We reviewed 128 SAB cases in 2011 and 124 in 2012. The majority of S. aureus were methicillin-susceptible (97/128, 75.8 % in 2011 and 100/124, 80.6 % in 2012). ID involvement increased significantly from 93/128 (72.7 %) in 2011, to 103/124 (83.1 %) in 2012 (odds ratio [OR] 1.9, 95 % confidence interval [CI] 1.1-3.3, p = 0.047). There was also a significant decrease in the median time to ID involvement from 2 days to 1 (p = 0.001). In patients who survived the minimum treatment course (greater than 13 days), there was a significant improvement in adherence to IDSA guidelines in 2012 (65/102, 63.7 % vs. 77/96, 80.2 %; OR 2.3, 95 % CI 1.2-4.4, p = 0.01). Mortality and SAB relapse rates were similar in both groups. CONCLUSIONS: Creating an automated ID consultation for SAB led to an increase in involvement of ID, a significant decrease in time to ID involvement, and better adherence to IDSA guidelines. The study was not sufficiently powered to detect significant changes in mortality and SAB relapse rates. PMID- 26666461 TI - Simultaneous selection and counter-selection for the directed evolution of proteases in E. coli using a cytoplasmic anchoring strategy. AB - With the goal of generating new enzymes that can cleave custom sequences, this article describes a selection strategy for evolving proteases with desirable characteristics. Positive selection and counter-selection are combined to select for and against specified cleavage sequences simultaneously. Cleavage of the positive selection sequence permits E. coli growth, and cleavage of the counter selection sequence slows growth. Growth occurs when cleavage of the positive selection sequence releases beta-lactamase into the periplasm where it can confer antibiotic resistance. The counter-selection traps beta-lactamase in the cytoplasm, preventing antibiotic resistance and growth. Thus, proteases with a preference for the positive selection sequence relative to the counter-selection sequence grow more rapidly. This system was used to select a tobacco etch virus (TEV) protease mutant with new substrate compatibility. Biotechnol. Bioeng. 2016;113: 1187-1193. (c) 2015 Wiley Periodicals, Inc. PMID- 26666460 TI - Vascular hepoxilin and trioxilins mediate vasorelaxation through TP receptor inhibition in mouse arteries. AB - AIM: 12/15-lipoxygenase (12/15-LO) metabolizes arachidonic acid (AA) into several vasoactive eicosanoids. In mouse arteries, we previously characterized the enzyme's 15-LO metabolites 12(S)-hydroxyeicosatetraenoic acid (HETE), 15-HETE, hydroxyepoxyeicosatrienoic acids (HEETAs) and 11,12,15-trihydroxyeicosatrienoic acids (11,12,15-THETAs) as endothelium-derived relaxing factors. However, the observed 12-LO metabolites remained uncharacterized. The purpose of this study was to determine the structure and biological functions of eicosanoids generated by the enzyme's 12-LO activity. METHODS: Metabolites extracted from aortas of C57BL/6 male mice were separated using a series of reverse and normal phase chromatographic steps and identified as hepoxilin A3 , trioxilin A3 and trioxilin C3 by mass spectrometry. Activities of these natural compounds were tested on isometric tension and intracellular calcium release. The role of thromboxane (TP) receptor was determined in HEK293 cells overexpressing TPalpha receptor (TPalpha HEK). RESULTS: All identified vascular 12-LO metabolites were biologically active. In mouse mesenteric arteries, trioxilin A3 , C3 and hepoxilin A3 (3 MUm) relaxed arteries constricted with the thromboxane mimetic, U46619-constricted arteries (maximum relaxations of 78.9 +/- 3.2, 29.7 +/- 4.6, 82.2 +/- 5.0 and 88.0 +/- 2.4% respectively), but not phenylephrine-constricted arteries. In TPalpha-HEK cells, trioxilin A3 , C3 and hepoxilin A3 (10 MUm) inhibited U46619 (10 nM)-induced increases in intracellular calcium by 53.0 +/- 7.2%, 32.8 +/- 5.0% and 37.9 +/- 13.5% respectively. In contrast, trioxilin B3 and hepoxilin B3 were not synthesized in arteries and exhibited little biological activity. CONCLUSION: Trioxilin A3 and C3 and hepoxilin A3 are endogenous vascular relaxing factors. They are not endothelium-derived hyperpolarizing factors but mediate vascular relaxation by inhibiting TP agonist-induced increases in intracellular calcium. Thus, they regulate vascular homeostasis by acting as endogenous TP antagonists. PMID- 26666462 TI - Antifungal Saponins from the Maya Medicinal Plant Cestrum schlechtendahlii G. Don (Solanaceae). AB - Bioassay-guided fractionation of the crude extract (80% EtOH) of the leaves of Cestrum schlechtendahlii, a plant used by Q'eqchi' Maya healers for treatment of athlete's foot, resulted in the isolation and identification of two spirostanol saponins (1 and 2). Structure elucidation by MS, 1D-NMR, and 2D-NMR spectroscopic methods identified them to be the known saponin (25R)-1beta,2alpha-dihydroxy 5alpha-spirostan-3-beta-yl-O-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D galactopyranoside (1) and new saponin (25R)-1beta,2alpha-dihydroxy-5alpha spirostan-3-beta-yl-O-beta-D-galactopyranoside (2). While 2 showed little or no antifungal activity at the highest concentration tested, 1 inhibited growth of Saccharomyces cerevisiae (minimum inhibitory concentration (MIC) of 15-25 MUM), Candida albicans, Cryptococcus neoformans, and Fusarium graminearum (MIC of 132 198 MUM). PMID- 26666463 TI - The use of statistical methodology to determine the accuracy of grading within a diabetic retinopathy screening programme. AB - AIMS: We aimed to use longitudinal data from an established screening programme with good quality assurance and quality control procedures and a stable well trained workforce to determine the accuracy of grading in diabetic retinopathy screening. METHODS: We used a continuous time-hidden Markov model with five states to estimate the probability of true progression or regression of retinopathy and the conditional probability of an observed grade given the true grade (misclassification). The true stage of retinopathy was modelled as a function of the duration of diabetes and HbA1c . RESULTS: The modelling dataset consisted of 65 839 grades from 14 187 people. The median number [interquartile range (IQR)] of examinations was 5 (3, 6) and the median (IQR) interval between examinations was 1.04 (0.99, 1.17) years. In total, 14 227 grades (21.6%) were estimated as being misclassified, 10 592 (16.1%) represented over-grading and 3635 (5.5%) represented under-grading. There were 1935 (2.9%) misclassified referrals, 1305 were false-positive results (2.2%) and 630 were false-negative results (11.0%). Misclassification of background diabetic retinopathy as no detectable retinopathy was common (3.4% of all grades) but rarely preceded referable maculopathy or retinopathy. CONCLUSION: Misclassification between lower grades of retinopathy is not uncommon but is unlikely to lead to significant delays in referring people for sight-threatening retinopathy. PMID- 26666465 TI - Assessment of Subclinical Atherosclerosis Using Computed Tomography Calcium Scores in Patients with Familial and Nonfamilial Hypercholesterolemia. AB - AIM: The aim of this study was to compare coronary calcium scores and aortic calcium scores between patients with severe hypercholesterolemia having a DNA based diagnosis of FH (FH group) versus patients with severe hypercholesterolemia without the FH gene mutation (NFH group). METHOD: A total of 89 FH and 50 NFH patients underwent CT with coronary and thoracic aorta calcium scoring. Their CCS and TCS in ascending aorta (TCSasc) and descending aorta (TCSdesc) were determined and compared between the two patient groups. RESULTS: TCSasc was significantly higher in the FH group when compared to the NFH group (30.6+/- 59 vs 4.7+/-13.4, p<0.001. After adjusting for age, sex, smoking, blood pressure, history of diabetes mellitus and LDL cholesterol levels, FH gene mutation was an independent risk factor of having non-zero TCSasc 3.6 (95% CI, 1.4-9.5, p<0.01), high TCSasc 9.6 (95% CI, 2.4-38.2, p<0.01) and high CCS of 4.1 (95% CI, 1.2-13.2. p<0.05). CONCLUSION: We found that when computed tomography calcium scores were used as an assessment, patients with familial hypercholesterolemia displayed an increased burden of ascending aorta atherosclerosis when compared to patients with nonfamilial severe hypercholesterolemia. This phenomenon appears to be more dependent on the presence of FH genotype than hypercholesterolemia itself. PMID- 26666464 TI - Characteristic Distribution Pattern of Lysophosphatidylcholine in Fibromuscular Dysplasia-Associated Visceral Artery Aneurysms Compared with Atherosclerotic Visceral Artery Aneurysms. AB - AIM: Asymptomatic visceral artery aneurysms (VAAs) have increasingly been found, with most being either atherosclerotic VAAs or fibromuscular dysplasia (FMD) associated VAAs. However, little is known about the pathogenesis of both diseases. We aimed to identify the differences in the distribution pattern of lipid molecules between atherosclerotic VAAs and FMD-associated VAAs. METHODS: We conducted a histological study of VAAs using imaging mass spectrometry (IMS) to assess the accumulation of lipid molecules in both the aneurysmal sac and the adjacent arteries without aneurysmal changes in 17 VAA samples, which were resected during the surgery. RESULTS: IMS revealed characteristic distributions of cholesterol ester in intima and media in the atherosclerotic VAAs, which was hardly detected in FMD-associated VAAs. However, lysophosphatidylcholine (lysoPC), a proinflammatory and proapoptotic lipid mediator, was accumulated in the medial ridge of the adventitia of FMD-associated in the aneurysmal sac, and it was also diffusely accumulated in the adjacent arteries. In contrast, lysoPC was accumulated in the area of intimal hyperplasia in atherosclerotic VAAs and the adjacent arteries. CONCLUSION: The distribution patterns of lipid molecules were different between the FMD-associated and atherosclerotic VAAs. The diffuse accumulation of lysoPCs in the visceral arteries may be a predisposition for the formation of FMD-associated VAAs. PMID- 26666466 TI - Vertically-Aligned Single-Crystal Nanocone Arrays: Controlled Fabrication and Enhanced Field Emission. AB - Metal nanostructures with conical shape, vertical alignment, large ratio of cone height and curvature radius at the apex, controlled cone angle, and single crystal structure are ideal candidates for enhancing field electron-emission efficiency with additional merits, such as good mechanical and thermal stability. However, fabrication of such nanostructures possessing all these features is challenging. Here, we report on the controlled fabrication of large scale, vertically aligned, and mechanically self-supported single-crystal Cu nanocones with controlled cone angle and enhanced field emission. The Cu nanocones were fabricated by ion-track templates in combination with electrochemical deposition. Their cone angle is controlled in the range from 0.3 degrees to 6.2 degrees by asymmetrically selective etching of the ion tracks and the minimum tip curvature diameter reaches down to 6 nm. The field emission measurements show that the turn on electric field of the Cu nanocone field emitters can be as low as 1.9 V/MUm at current density of 10 MUA/cm(2) (a record low value for Cu nanostructures, to the best of our knowledge). The maximum field enhancement factor we measured was as large as 6068, indicating that the Cu nanocones are promising candidates for field emission applications. PMID- 26666467 TI - Artificial neural network-based pharmacogenomic algorithm for warfarin dose optimization. AB - AIM: To develop more precise pharmacogenomic algorithm for prediction of safe and effective dose of warfarin. MATERIALS & METHODS: An artificial neural network (ANN) algorithm was developed by using age, gender, BMI, plasma vitamin K levels, thyroid status and ten genetic variables as the inputs and therapeutic warfarin dose as the output. Hyperbolic tangent function was used to build an ANN architecture. RESULTS: This model explained 93.5% variability in warfarin dosing and predicted warfarin dose accurately in 74.5% patients whose international normalized ratio (INR) was less than 2.0 and in 83.3% patients whose INR was more than 3.5. This algorithm reduced the out-of-range INRs (odds ratio [OR]: 0.49; 95% CI: 0.30-0.79; p = 0.003), the rate of adverse drug reactions (OR: 0.00; 95% CI: 0.00-1.21; p = 0.06) and time to reach first therapeutic INR (OR: 6.73; 95% CI: 2.17-22.31; p < 0.0001). This algorithm was found to be applicable in both euthyroid and hypothyroid status. S-warfarin/7-hydroxywarfarin ratio was found to increase in subjects with CYP2C9*2 and CYP2C9*3 justifying the warfarin sensitivity attributed to these variants. CONCLUSION: An application of ANN for warfarin dosing improves predictability and provides safe and effective dosing. PMID- 26666468 TI - Synthesis of Branched Alkylboronates by Copper-Catalyzed Allylic Substitution Reactions of Allylic Chlorides with 1,1-Diborylalkanes. AB - Reported herein is a copper-catalyzed S(N)2'-selective allylic substitution reaction using readily accessible allylic chlorides and 1,1-diborylalkanes, a reaction which proceeds with chemoselective C-B bond activation of the 1,1 diborylalkanes. In the presence of a catalytic amount of [Cu(IMes)Cl] [IMes=1,3 bis(2,4,6-trimethylphenyl)imidazole-2-ylidene] and LiOtBu as a base, a range of primary and secondary allylic chlorides undergo the S(N)2'-selective allylic substitution reaction to produce branched alkylboronates. The synthetic utilities of the obtained alkylboronates are also presented. PMID- 26666469 TI - Responses of photosynthetic parameters to drought in subtropical forest ecosystem of China. AB - The mechanism underlying the effect of drought on the photosynthetic traits of leaves in forest ecosystems in subtropical regions is unclear. In this study, three limiting processes (stomatal, mesophyll and biochemical limitations) that control the photosynthetic capacity and three resource use efficiencies (intrinsic water use efficiency (iWUE), nitrogen use efficiency (NUE) and light use efficiency (LUE)), which were characterized as the interactions between photosynthesis and environmental resources, were estimated in two species (Schima superba and Pinus massoniana) under drought conditions. A quantitative limitation analysis demonstrated that the drought-induced limitation of photosynthesis in Schima superba was primarily due to stomatal limitation, whereas for Pinus massoniana, both stomatal and non-stomatal limitations generally exhibited similar magnitudes. Although the mesophyll limitation represented only 1% of the total limitation in Schima superba, it accounted for 24% of the total limitations for Pinus massoniana. Furthermore, a positive relationship between the LUE and NUE and a marginally negative relationship or trade-off between the NUE and iWUE were observed in the control plots. However, drought disrupted the relationships between the resource use efficiencies. Our findings may have important implications for reducing the uncertainties in model simulations and advancing the understanding of the interactions between ecosystem functions and climate change. PMID- 26666470 TI - Vocal cord dysfunction diagnosis may be improved by a screening check list. AB - BACKGROUND: Many patients with vocal cord dysfunction (VCD), with or without asthma, receive inappropriate treatment because they are misdiagnosed as having difficult-to-control asthma alone. We developed a clinical screening check list designed to aid the diagnosis of VCD. METHODS: A prospective observational study involving 80 patients aged >=18 years, diagnosed with severe asthma. After anamnesis and physical examination, physicians completed a check list with 6 questions to identify VCD, for which the answer "yes" counted one point. Then patients underwent spirometry and laryngoscopy. On the basis of the laryngoscopic findings, we created three patient groups: VCD (vocal cord adduction during inspiration, n = 14); unconfirmed VCD (inconclusive findings, n = 29); and control (normal findings, n = 37). We attempted to determine whether any of those groups were associated with the responses to individual questions or sets of questions on the check list. RESULTS: The proportion of affirmative answers to the question "Does pulmonary auscultation reveal wheezing, predominantly in the cervical region, and/or stridor?" was significantly higher for the VCD group than for the other two groups (P = 0.006), notably in elderly patients. The variable "4 or more affirmative answers" was more common in VCD and unconfirmed VCD groups in comparison to controls (P = 0.022). CONCLUSIONS: A finding of wheezing or stridor on auscultation of the cervical region is suggestive of vocal cord dysfunction, especially in elderly patients, and such dysfunction can be confirmed through laryngoscopy. Our VCD screening check list proved to be useful in the screening of VCD among patients with severe asthma. PMID- 26666471 TI - Epidemiology of pediatric allergic diseases in the Ogasawara Islands. AB - BACKGROUND: The Ogasawara Islands, away from mainland Japan, belong to a subtropical area. Although the daily eating habits and food are relatively similar to that on the mainland, the living environment is quite different. The prevalence of allergic diseases in the Ogasawara Islands is unknown. This study aimed to identify the prevalence of allergic diseases in the Ogasawara Islands. METHODS: A survey was conducted among all children belonging to preschool, elementary school, and junior high school in the Ogasawara Islands. A questionnaire was prepared in accordance with the International Study of Asthma and Allergies in Childhood (ISAAC) core written questionnaire in bronchial asthma (BA) and the West Japan Study of Asthma and Allergies in Childhood core written questionnaire for atopic dermatitis (AD), allergic rhinitis (AR), and food allergy (FA). At the same time, height, weight, duration of dwelling on the island, home environment, lifestyle, and exercise habits were also asked. RESULTS: The target population comprised 352 children, of whom 284 (80.6%) completed the questionnaires. The current prevalence was 9.3% for BA, 4.3% for AD, 17.8% for AR, and 3.0% for FA. Significantly lower rates of current BA and AD were observed compared to previous reports from Japan. The percentage of children belonging to sports clubs, and exercising more than 3 times per week at the Ogasawara Islands is higher compared with the national average. CONCLUSIONS: The lower prevalence of BA and AD in the Ogasawara Islands implies the influence of differences in the living environment and exercise habits. PMID- 26666472 TI - Occupational allergic asthma induced by Liposcelis decolor. PMID- 26666473 TI - Natural history of immediate-type hen's egg allergy in Japanese children. AB - BACKGROUND: Hen's egg (HE) allergy develops during infancy. We investigated tolerance acquisition in Japanese children allergic to HE aging <6 years. METHODS: In this retrospective study, 226 children born in 2005 with a history of immediate-type HE allergy underwent an oral food challenge (OFC). Tolerance was defined as no reaction to an OFC with half of whole heated HE or accidental HE consumption at home. Participants were divided into three groups based on age at tolerance acquisition: group I (<3 years) (n = 66), group II (3-6 years) (n = 98), and group III (prolonged allergic groups) (n = 62). RESULTS: Tolerance acquisition occurred in 30% (66/226) by 3 years of age, 59% (133/226) by 5 years of age, and 73% (164/226) at 6 years of age. At 3 years, incidences of allergy related complications (bronchial asthma, p = 0.02; atopic dermatitis, p = 0.04) were higher in the group III than in the group I. Anaphylaxis to any food occurred more frequently in the group III than in the group I (p = 0.03); anaphylaxis to HE was more common in the group III (p = 0.04). Egg white (EW)- and ovomucoid (OM)-specific immunoglobulin E (IgE) levels were higher in the group III than in the group I (p < 0.05). CONCLUSIONS: The group III experienced HE-related anaphylaxis and complications more frequently and exhibited sustained, high EW- and OM-specific IgE levels. PMID- 26666474 TI - IL-33 promotes ICAM-1 expression via NF-kB in murine mast cells. AB - BACKGROUND: IL-33, a member of the IL-1 cytokine family, binds to heterodimeric receptors ST2 and IL-1 receptor accessory protein, and activates Th2-type immune responses. The signals from the ST2 receptor are mediated by the two major pathways, including AP-1 and NF-kappaB molecules. The present study examined whether IL-33 induced ICAM-1 expression in bone marrow-derived mast cells (BMMCs). METHODS: BMMCs from C57BL/6J mice, cultured in media containing IL-3 (20 ng/ml), were treated with IL-33 (50 ng/ml) for up to 72 h. ICAM-1 expression with mRNA and protein, degranulation of siRNA ICAM-1 transfected BMMCs, and cell adhesion were analyzed. In the in vivo part of the experiment rIL-33 (500 ng) was injected intradermally into the ear pinnae of mice and any resulting pathological changes were assessed. RESULTS: ICAM-1 mRNA expression was increased one hour after IL-33 stimulation while ICAM-1 protein attained maximum expression levels 24 h after IL-33 stimulation. Moreover, IL-33-treated BMMCs showed increased cell adhesion to the LFA-1-coated plate. However, siRNA ICAM-1 transfected BMMCs did not affect Ag/IgE-mediated degranulation level compared to the wild control siRNA. Pre-treatment with a NF-kappaB inhibitor dramatically reduced ICAM-1 expression in IL-33-treated BMMCs, suggesting the involvement of NF-kappaB in the process. In vivo study, at 6 h after IL-33 treatment, MCs histologically showed up-regulated ICAM-1 expression though the number of tryptase-positive cells did not change. CONCLUSIONS: These data suggest that MCs increase ICAM-1 expression and activate LFA-1 positive cells in the early phase of skin inflammation in response to IL-33. PMID- 26666475 TI - A case of refractory Kimura disease with a buccal bulky mass successfully treated with low-dose cyclosporine A: report and review of the literature. PMID- 26666476 TI - Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice. AB - BACKGROUND: The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite induced intractable AD using an NC/Nga mouse model. METHODS: Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). RESULTS: Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. CONCLUSIONS: FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function. PMID- 26666478 TI - Increased circulating Th17 cell in a patient with tinea capitis caused by Microsporum canis. PMID- 26666477 TI - Delayed anaphylaxis to alpha-gal, an oligosaccharide in mammalian meat. AB - IgE-mediated hypersensitivity refers to immune reactions that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. To that end, identification of the associated allergen is important for facilitating both education and allergen avoidance that are essential to long-term risk reduction. As the number of known exposures associated with anaphylaxis is limited, discovery of novel causative agents is crucial to evaluation and management of patients with idiopathic anaphylaxis. Within the last 10 years several apparently separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins. Interestingly, the exposure differed from airborne allergens but was nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose ("alpha-gal"). This review will present the historical summary of the identification of cetuximab hypersensitivity due to alpha-gal IgE and discuss the non-primate mammalian meat food allergy as well as current goals and directions of our research programs. PMID- 26666479 TI - Effect of Asian dust on pulmonary function in adult asthma patients in western Japan: A panel study. AB - BACKGROUND: Asian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 MUm (PM10) and 2.5 MUm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data. METHODS: Subjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR. RESULTS: Increases in the interquartile range of AD particles (0.018 km(-1)) led to changes in PEF of -0.42 L/min (95% confidence interval [CI], -0.85 to 0.01). An increase of 11.8 MUg/m(3) in suspended particulate matter and 6.9 MUg/m(3) in PM2.5 led to decreases of -0.17 L/min (-0.53 to 0.21) and 0.03 L/min (-0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km(-1), which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was -0.97 L/min (-1.90 to -0.04). CONCLUSIONS: Heavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients. PMID- 26666480 TI - High incidence of ANCA-positive Interstitial Pneumonia after the 2011 Fukushima disaster. PMID- 26666481 TI - Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations. AB - BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Few studies have used noninvasive techniques to measure epidermis function in asymptomatic neonates. METHODS: Data of 116 infants from our previous randomized controlled study were analyzed. Skin barrier function was measured through transepidermal water loss (TEWL), stratum corneum hydration (SCH), and pH. The association between skin barrier function and time to AD development was evaluated. Patients were classified with high or low TEWL, and SCH and pH were assessed. The survival function of the time to AD development and hazard ratios were estimated. Allergic sensitization to egg white and ovomucoid at 32 weeks was assessed. RESULTS: Regardless of a filaggrin mutation, TEWL (optimal cutoff, 6.5 g/m(2)/h) of the forehead within the first week of life showed a lower p-value than TEWL of the leg, and the SCH and pH measurements. Baseline TEWL of the forehead was not different between groups, except for the mean gestational age, and it was not affected by humidity. We found a significant difference in the cumulative AD incidence between the high and low TEWL groups for the forehead only (p < 0.05). The probability without AD was lower in the high TEWL group than in the low TEWL group. For only the high TEWL group, AD development decreased significantly with daily emollient use. The high TEWL group exhibited a higher rate of sensitization to ovomucoid (p = 0.07). CONCLUSIONS: TEWL of the forehead during the first week of life is associated with AD development. PMID- 26666482 TI - Mast cells and IgE in defense against venoms: Possible "good side" of allergy? AB - Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcERI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances. PMID- 26666483 TI - Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients--Treatment and outcome. AB - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. METHODS: To present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000-2013. RESULTS: Fifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000-2006 and 2007-2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN. CONCLUSIONS: Treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN. PMID- 26666484 TI - Angiotensin-converting enzyme genotype is a risk factor for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat protein. PMID- 26666485 TI - Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-gamma production in chronic rhinosinusitis with nasal polyps. AB - BACKGROUND: Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs). METHODS: DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-gamma in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined. RESULTS: Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-gamma by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL 13 and IL-17A, but not IFN-gamma production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs. CONCLUSIONS: These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production. PMID- 26666486 TI - Fragmented gelsolins are increased in rheumatoid arthritis-associated interstitial lung disease with usual interstitial pneumonia pattern. AB - BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) occurs in 10%-30% of patients with RA, and interstitial lung disease (ILD) is associated with increased mortality in up to 10% of patients with RA. The pathogenesis of RA-ILD is virtually unknown. The aim of this study is to investigate the proteins related to UIP pattern by comparing to OP pattern in RA ILD using proteome analysis of bronchoalveolar lavage fluid (BALF). METHODS: Proteomic differences in BALF were compared between the UIP pattern and OP pattern by examining BALF from 5 patients with the UIP pattern and 7 patients with the OP pattern by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: In individual comparisons of BALF samples, the levels of the protein gelsolin and Ig kappa chain C region were significantly higher in the UIP pattern than in the OP pattern. In contrast, the levels of alpha-1 antitrypsin, CRP, haptoglobin beta, and surfactant protein A (isoform number 5) were all significantly higher in the OP pattern than in the UIP pattern. Gelsolin was cleaved into two fragments, a C-terminal half and N-terminal half, and the levels of both were significantly higher in the UIP pattern than in the OP pattern. CONCLUSIONS: Fragmented gelsolins may be associated with the pathogenesis of fibrosis in RA-ILD. PMID- 26666487 TI - Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation. AB - Allergic disorders commonly involve both chronic tissue inflammation and remodeling caused by immunological reactions to various antigens on tissue surfaces. Due to their anatomical location, vascular endothelial cells are the final responders to interact with various exogenous factors that come into contact with the epithelial surface, such as pathogen-associated molecular patterns (PAMPs) and antigens. Recent studies have shed light on the important roles of endothelial cells in the development and exacerbation of allergic disorders. For instance, endothelial cells have the greatest potential to produce several key molecules that are deeply involved in allergic inflammation, such as periostin and thymus and activation-regulated chemokine (TARC/CCL17). Additionally, endothelial cells were recently shown to be important functional targets for IL-33--an essential regulator of allergic inflammation. Notably, almost all endothelial cell responses and functions involved in allergic inflammation are not suppressed by corticosteroids. These corticosteroid refractory endothelial cell responses and functions include TNF-alpha-associated angiogenesis, leukocyte adhesion, IL-33-mediated responses and periostin and TARC production. Therefore, these unique responses and functions of endothelial cells may be critically involved in the pathogenesis of various allergic disorders, especially their refractory processes. Here, we review recent studies, including ours, which have elucidated previously unknown pathophysiological roles of vascular endothelial cells in allergic inflammation and discuss the possibility of endothelium-targeted therapy for allergic disorders. PMID- 26666488 TI - Prevalence of childhood asthma in Ulaanbaatar, Mongolia in 2009. AB - BACKGROUND: Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia-Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. METHODS: The asthma prevalence and patient background information in Mongolian children aged 6-7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. CONCLUSIONS: The asthma prevalence in Mongolian children was higher than that in the world and Asia-Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma. PMID- 26666489 TI - Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents. AB - BACKGROUND: Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. METHODS: Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. RESULTS: We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). CONCLUSIONS: Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. PMID- 26666490 TI - Better management of wheat allergy using a very low-dose food challenge: A retrospective study. AB - BACKGROUND: Low-dose reactive wheat-allergic children are at a high risk of a positive oral food challenge (OFC). The present study aimed to evaluate whether the results of a very low-dose (VL) OFC would contribute to better wheat allergy management in this population. METHODS: We retrospectively reviewed wheat allergic subjects who underwent a VL OFC with 2 g of udon noodles (equivalent to 53 mg of wheat protein) and had a previous allergic reaction to <15 g of udon noodles (equivalent to 400 mg of wheat protein) within 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant; those who failed were considered VL reactive. In VL tolerant subjects, the dose was increased to 15 g of udon noodles either during an OFC in our hospital or gradually at home. RESULTS: Of the 57 included subjects (median age, 2.9 years; range, 1.0-11.8 years), 32 (56%) were VL tolerant and 25 (44%) were VL reactive. Most reactions during the OFC could be treated with an antihistamine and/or a nebulized beta2 agonist. VL tolerant subjects consumed 2 g of udon noodles or a seasoning containing wheat. Within a year after the OFC, 18 VL tolerant subjects (56%), but no VL reactive subjects, were able to consume 15 g of udon noodles (p < 0.001). CONCLUSIONS: A VL OFC can shift the management of some low-dose reactive wheat allergic children from complete avoidance to partial wheat intake. PMID- 26666491 TI - Remission rate of patients with wheat allergy sensitized to hydrolyzed wheat protein in facial soap. PMID- 26666492 TI - The severity of peripheral blood eosinophilia indicates an eosinophilia associated disease corresponding to its level. PMID- 26666493 TI - Anti-Ascaris immunoglobulin E associated with bronchial hyper-reactivity in 9 year-old rural Bangladeshi children. AB - BACKGROUND: Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper responsiveness (BHR) in children living in rural Bangladesh. METHODS: Serum anti Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. RESULTS: Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. CONCLUSIONS: Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children. PMID- 26666494 TI - Association between pulmonary function and daily levels of sand dust particles assessed by light detection and ranging in schoolchildren in western Japan: A panel study. AB - BACKGROUND: An important aspect of sand dust emissions in association with respiratory disorders is the quantity of particulate matter. This is usually expressed as particulate matter less than 10 MUm (PM10) and 2.5 MUm (PM2.5). However, the composition of PM10 and PM2.5 varies. Light detection and ranging is used to monitor sand dust particles originating in East Asian deserts and distinguish them from air pollution aerosols. The objective of this study was to investigate the association between the daily levels of sand dust particles and pulmonary function in schoolchildren in western Japan. METHODS: In this panel study, the peak expiratory flow (PEF) of 399 schoolchildren was measured daily from April to May 2012. A linear mixed model was used to estimate the association of PEF with the daily levels of sand dust particles, suspended particulate matter (SPM), and PM2.5. RESULTS: There was no association between the daily level of sand dust particles and air pollution aerosols, while both sand dust particles and air pollution aerosols had a significant association with SPM and PM2.5. An increment of 0.018 km(-1) in sand dust particles was significantly associated with a decrease in PEF (-3.62 L/min; 95% confidence interval, -4.66 to -2.59). An increase of 14.0 MUg/m(3) in SPM and 10.7 MUg/m(3) in PM2.5 led to a significant decrease of -2.16 L/min (-2.88 to -1.43) and -2.58 L/min (-3.59 to -1.57), respectively, in PEF. CONCLUSIONS: These results suggest that exposure to sand dust emission may relate to pulmonary dysfunction in children in East Asia. PMID- 26666495 TI - Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice. AB - BACKGROUND: Patients with house dust mite (HDM) allergy or Ascariasis produce serum IgE specific to the antigens of HDM or nematode Ascaris, respectively. Although human IgE cross-reactivity has been reported between HDM and Ascaris antigens, it remains unclear whether it contributes to the pathogenesis of allergic diseases. We herein investigated the induction of cross-reactive antibodies and T cells in mice and effects of airway exposure to HDM antigens after preimmunization with Ascaris antigens. METHODS: Mice were intraperitoneally immunized with HDM or Ascaris antigens with Alum, followed by the intranasal administration of HDM antigens. Serum antigen-specific IgE and IgG were measured by ELISA. Cytokine release in splenocytes from Ascaris-immunized mice upon in vitro restimulation with HDM antigens were measured by ELISA. RESULTS: Immunization with Ascaris or HDM antigens induced cross-reactive IgG1. Splenocytes from Ascaris-immunized mice released IL-5 and IL-13 in response to the restimulation with HDM antigens. Subsequent airway exposure to HDM antigens promoted the induction of HDM-specific IgE and upregulation of HDM-specific IgG1 in Ascaris-immunized mice, whereas these responses were not detected or smaller without the Ascaris presensitization. CONCLUSIONS: We demonstrated that the immunization of naive mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris. PMID- 26666496 TI - Allergies are still on the rise? A 6-year nationwide population-based study in Korea. AB - BACKGROUND: Some western countries recently have shown a slowdown in the incidence of allergic diseases after worldwide increasing trends, but there are few data from Asian populations concerning changing trend of allergic diseases. We evaluated the recent trends in the prevalence of asthma and other allergic diseases in Korea. METHODS: From the database of Korean National Health Insurance, a nationwide diagnostic data from 2009 to 2014 were extracted and the national prevalence was analyzed. RESULTS: The prevalence per 1000 people of atopic dermatitis, allergic rhinitis, and asthma in 2014 was 19.0, 133.1, and 36.3, respectively. The prevalence of three diseases was highest in the age group under 10 as, 95.0, 384.1, and 132.1 per 1000 people, while the prevalence in the over-10-year-group was only 11.6, 109.5, and 27.3, respectively. The prevalence of atopic dermatitis and allergic rhinitis gradually decreased with older age, but the prevalence of asthma showed a re-increasing pattern from the age group 30 39 and reached another peak for the age group 70-79. During the study period, the prevalence of asthma and atopic dermatitis showed decreasing tendency. In contrast, the prevalence of allergic rhinitis steadily increased until 2013, especially in the age group under 10. CONCLUSIONS: The national prevalence of atopic dermatitis, and asthma did not show noticeable increase any more in Korea. However, the prevalence of allergic rhinitis still on the rise until recently, especially in the age group under 10. This is the first report in Asia suggesting a slowdown of the incidence of allergic diseases. PMID- 26666499 TI - Different impact of hemodialysis vintage on cause-specific mortality in long-term hemodialysis patients. AB - BACKGROUND: Although dialysis vintage is associated with increased mortality risk in patients receiving hemodialysis (HD), the association of dialysis vintage with cause-specific mortality is unclear. METHODS: We conducted a nationwide registry based retrospective cohort study of 216 246 patients receiving maintenance HD for > 1 year at the end of 2009. The associations of dialysis vintage categories (1 < 2, 2 -< 5, 5 -< 10, 10 -< 15, 15 -< 20, 20 -< 25, 25 -< 30 and >= 30 years) with 1-year all-cause and cause-specific mortality, including cardiovascular diseases (CVDs) and infection-related mortality, were examined using logistic regression models. RESULTS: During the 1-year study period, 18 614 deaths occurred from all causes, including 7263 and 3504 deaths from CVD and infection related causes. From multivariate analysis, the dialysis vintage was incrementally associated with a higher risk for all-cause mortality, with worse outcome observed in the >= 30 years category {odds ratio [OR] = 2.43 (95% confidence interval (CI) 2.13-2.77}. A similar association was apparent between the dialysis vintage and infection-related mortality, with a higher risk than that of all-cause mortality in each vintage category [>= 30 years, OR = 3.55 (95% CI 2.72-4.66)], while the dialysis vintage was associated with only a modest increase in risk of CVD mortality [>= 30 years, OR = 1.64 (95% CI 1.30-2.08)]. CONCLUSIONS: Dialysis vintage has a different impact on cause-specific mortality, with a higher risk for infection-related mortality than CVD mortality. This impact is most pronounced in long-term HD survivors, to whom much attention should be devoted to prevent infectious complications. PMID- 26666498 TI - Elevation of circulating but not myocardial FGF23 in human acute decompensated heart failure. AB - BACKGROUND: Elevated plasma fibroblast growth factor 23 (FGF23) is a prognostic marker in chronic kidney disease. Recently, FGF23 was reported to also be a predictive factor in chronic congestive heart failure (HF). To date however, plasma levels in acute decompensated HF (ADHF) have not been reported and myocardial production and distribution of FGF23 in HF is poorly defined. We aimed to determine plasma levels and myocardial production of FGF23 in ADHF. METHODS: Plasma FGF23, N-terminal pro B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) were assessed in 21 ADHF patients and 19 controls. Myocardial gene expression and distribution of FGF23 was determined on left ventricular samples from HF patients and normal controls. RESULTS: Plasma FGF23 was markedly higher in ADHF patients compared with controls (1498 +/- 1238 versus 66 +/- 27 RU/mL, P < 0.0001). There were no correlations between FGF23 and eGFR, NT-proBNP, ejection fraction or age. ADHF subjects with eGFR >60 mL/min/1.73 m(2) had FGF23 levels of 1526 +/- 1601 RU/mL versus 55 +/- 20 RU/mL in controls (P = 0.007). Quantified myocardial FGF23 gene expression was similar between HF patients and controls. Myocardial FGF23 immunostaining was similar between HF patients and controls, with equal distribution throughout cardiomyocytes. CONCLUSION: Patients with ADHF had markedly elevated plasma FGF23 levels. Myocardial FGF23 gene expression was present in HF at a similar level as normal controls, and immunohistochemistry showed similar cellular distribution of FGF23 in HF and controls, suggesting that the myocardium does not contribute to the elevated circulating FGF23 in HF. PMID- 26666500 TI - Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. AB - OBJECTIVE: To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1). METHODS: Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (>=16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score >=30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study. Symptoms of myoclonus were assessed by Unified Myoclonus Rating Scale (UMRS). Primary efficacy end point was percent reduction from baseline in action myoclonus score (UMRS section 4) at last treatment visit. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: N01187: 50 patients randomized, 47 completed; N01236: 56 patients randomized, 54 completed. Median (min-max) percent reduction from baseline in action myoclonus score is the following-N01187: placebo 5.6 (-81.3 to 53.8), pooled BRV group (primary efficacy analysis) 21.4 (-50.0 to 73.6), BRV 50 mg/day 26.3 (-35.8 to 69.2), BRV 150 mg/day 16.9 (-50.0 to 73.6); N01236: placebo 17.5 (-170 to 61.5), BRV 5 mg/day -4.6 (-430 to 81.8), BRV 150 mg/day (primary efficacy analysis) 12.3 (-58.3 to 96.9). Estimated differences versus placebo were not statistically significant. TEAEs were reported by 72-75% placebo-treated and 56-83% BRV-treated patients. SIGNIFICANCE: Effect of BRV on action myoclonus was not statistically significant. However, action myoclonus score showed wide intrapatient variability and may not have been the optimal tool to measure severity of myoclonus in EPM1. Both studies had very high completion rates (95.3% overall), and a high percentage of patients (88.7% overall) entered long-term follow-up; both likely to be influenced by good tolerability. These studies demonstrate the feasibility of rigorous trials in progressive myoclonic epilepsy. PMID- 26666501 TI - Sedimentary archaeal amoA gene abundance reflects historic nutrient level and salinity fluctuations in Qinghai Lake, Tibetan Plateau. AB - Integration of DNA derived from ancient phototrophs with their characteristic lipid biomarkers has been successfully employed to reconstruct paleoenvironmental conditions. However, it is poorly known that whether the DNA and lipids of microbial functional aerobes (such as ammonia-oxidizing archaea: AOA) can be used for reconstructing past environmental conditions. Here we identify and quantify the AOA amoA genes (encoding the alpha subunit of ammonia monooxygenases) preserved in a 5.8-m sediment core (spanning the last 18,500 years) from Qinghai Lake. Parallel analyses revealed that low amoA gene abundance corresponded to high total organic carbon (TOC) and salinity, while high amoA gene abundance corresponded to low TOC and salinity. In the Qinghai Lake region, TOC can serve as an indicator of paleo-productivity and paleo-precipitation, which is related to historic nutrient input and salinity. So our data suggest that temporal variation of AOA amoA gene abundance preserved in Qinghai Lake sediment may reflect the variations of nutrient level and salinity throughout the late Pleistocene and Holocene in the Qinghai Lake region. PMID- 26666502 TI - Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder. AB - The amygdala is a complex structure with distinct subregions and dissociable functional networks. The laterobasal subregion of the amygdala is hypothesized to mediate the presentation and severity of autism symptoms, although very little data are available regarding amygdala dysfunction at the subregional level. In this study, we investigated the relationship between abnormal amygdalar intrinsic connectivity, autism symptom severity, and anxiety and depressive symptoms. We collected resting state fMRI data on 31 high functioning adolescents and adults with autism spectrum disorder and 38 typically developing (TD) controls aged 14 45. Twenty-five participants with ASD and 28 TD participants were included in the final analyses. ASD participants were administered the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule. Adult participants were administered the Beck Depression Inventory II and the Beck Anxiety Inventory. Functional connectivity analyses were conducted from three amygdalar subregions: centromedial (CM), laterobasal (LB) and superficial (SF). In addition, correlations with the behavioral measures were tested in the adult participants. In general, the ASD group showed significantly decreased connectivity from the LB subregion and increased connectivity from the CM and SF subregions compared to the TD group. We found evidence that social symptoms are primarily associated with under-connectivity from the LB subregion whereas over connectivity and under-connectivity from the CM, SF and LB subregions are related to co-morbid depression and anxiety in ASD, in brain regions that were distinct from those associated with social dysfunction, and in different patterns than were observed in mildly symptomatic TD participants. Our findings provide new evidence for functional subregional differences in amygdala pathophysiology in ASD. Autism Res 2016, 9: 760-772. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26666503 TI - Heavy-heartedness biases your weight perception. AB - Heavy-heartedness (light-heartedness), among more than two hundred metaphors related to the heart, indicates negative (positive) affects. Although these metaphors are generally understood rhetorically, this study explores whether there is any literal connection between either of these two states and one's perception of weight. Participants who recalled a heavy-heartening (vs. light heartening) past event estimated more weight of an object (Study 1). While watching weightlifting and pole-vaulting competition clips, people in heavy hearted (vs. light-hearted) states predicted that players' success is less likely (Study 2). However, this result was not observed while people in both states watched non-weight-related games, such as golf-putting and pool. The findings are congruous with embodied cognition theory and the role of metaphors in our life. PMID- 26666504 TI - Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients. AB - BACKGROUND: Liver transplantation is an established treatment option for end stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. OBJECTIVES: To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Social Sciences Citation Index, The Transplant Library, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) until September 2014. SELECTION CRITERIA: Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver-transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding the perioperative period and excluding the occurrence of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. DATA COLLECTION AND ANALYSIS: We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed effect model and reported both results where a discrepancy existed. We assessed the risk of systematic errors using risk of bias domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table. MAIN RESULTS: We included 16 completed randomised clinical trials with a total of 1347 participants. We found 10 trials that assessed complete postoperative glucocorticosteroid avoidance (excluding intra-operative use and treatment of rejection) versus short-term glucocorticosteroids (782 participants) and six trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids (565 participants). We found one ongoing trial assessing complete postoperative glucocorticosteroid avoidance versus short-term glucocorticosteroids, which is expected to enrol 300 participants. All trials were at high risk of bias. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low-quality evidence), graft loss including death (RR 1.16, 95% CI 0.91 to 1.48; low-quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; low-quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression. Acute rejection and glucocorticosteroid-resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; moderate-quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low-quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low-quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low-quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta analyses. AUTHORS' CONCLUSIONS: Many of the benefits and harms of glucocorticosteroid avoidance or withdrawal remain uncertain because of the limited number of published randomised clinical trials, limited numbers of participants and outcomes, and high risk of bias in the trials. Glucocorticosteroid avoidance or withdrawal appears to reduce diabetes mellitus and hypertension whilst increasing acute rejection, glucocorticosteroid-resistant rejection, and renal impairment. We could identify no other benefits or harms of glucocorticosteroid avoidance or withdrawal. Glucocorticosteroid avoidance or withdrawal may be of benefit in selected patients, especially those at low risk of rejection and high risk of hypertension or diabetes mellitus. The optimal duration of glucocorticosteroid administration remains unclear. More randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal are needed. These should be large, high-quality trials that minimise the risk of random and systematic error. PMID- 26666505 TI - Postpartum uterine artery blood flow impedance following cesarean section or vaginal delivery. AB - PURPOSE: To compare uterine arteries (UtA) blood flow after cesarean section (CS) or vaginal delivery (VD). METHODS: We performed a prospective case-control study comparing UtA blood flow impedance in patients who delivered by CS or VD. The UtA pulsatility index (PI) was measured with Doppler ultrasound during post partum using a transabdominal convex probe. Maternal and gestational age, parity, gravidity, and delay between delivery and Doppler measurement were noted. RESULTS: We examined 106 postnatal patients, of whom 35 had CS delivery and 71 had VD. The median delay from delivery to Doppler measurement was 35 hours for the CS group and 32 hours for the VD group. The mean PI following CS and VD was 1.62 +/- 0.45 and 1.42 +/- 0.47, respectively. Using a linear model, the regression coefficients for mean, right, and left PI were not significantly different depending on the mode of delivery. There was no difference between emergency and elective CS. CONCLUSIONS: Early postpartum UtA blood flow impedance is not significantly different after CS or VD. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:278-283, 2016. PMID- 26666507 TI - Corrigendum. PMID- 26666506 TI - Comparative study of diversity based on heat tolerant-related morpho physiological traits and molecular markers in tall fescue accessions. AB - Heat stress is a critical challenge to tall fescue (Festuca arundinacea Schreb.) in many areas of the globe and variations in genetic structure and functional traits is for the efficient breeding programs on developing heat tolerant cultivars. Tolerant-related morpho-physiological traits and simple sequence repeat (SSR) markers were employed to survey genetic diversity in greenhouse and growth chamber trials. 100 tall fescue accessions, including 8 commercial cultivars and 92 natural genotypes, showed a high variation in phenotypic performance under heat stress. Based on standardized heat tolerant-related morpho physiological data, all tall fescue accessions were clustered into five groups. The accessions with similar heat tolerance were likely to be clustered in the same group. The highest genetic diversity was obtained for accessions from Africa judged by Nei's gene diversity (0.2640) and PIC (0.2112). All grass accessions could be divided into three major groups based on SSR markers, which was partially congruous to the geographical regions and history of introduction. A low correlation was found between morpho-physiological traits and SSR markers by Mantel test. The patterns in morpho-physiological trait variations and genetic diversity associated with heat tolerance were useful to design breeding programs for developing heat stress resistance in tall fescue. PMID- 26666508 TI - Effects of aerobic exercise training on fitness and walking-related outcomes in ambulatory individuals with chronic incomplete spinal cord injury. AB - STUDY DESIGN: Single group, pretest-post-test study. OBJECTIVES: To determine the effects of a non-task-specific, voluntary, progressive aerobic exercise training (AET) intervention on fitness and walking-related outcomes in ambulatory adults with chronic motor-incomplete SCI. SETTING: Rehabilitation research center. METHODS: Ten ambulatory individuals (50% female; 57.94+/-9.33 years old; 11.11+/ 9.66 years postinjury) completed voluntary, progressive moderate-to-vigorous intensity AET on a recumbent stepper 3 days per week for 6 weeks. The primary outcome measures were aerobic capacity (VO2peak (volume of oxygen that the body can use during physical exertion)) and self-selected overground walking speed (OGWS). Secondary outcome measures included walking economy, 6-minute walk test (6MWT), daily step counts, Walking Index for Spinal Cord Injury (WISCI-II), Dynamic Gait Index (DGI) and Berg Balance Scale (BBS). RESULTS: Nine participants completed all testing and training. Significant improvements in aerobic capacity (P=0.011), OGWS (P=0.023), the percentage of VO2peak used while walking at self selected speed (P=0.03) and daily step counts (P=0.025) resulted following training. CONCLUSIONS: The results indicate that total-body, voluntary, progressive AET is safe, feasible, and effective for improving aerobic capacity, walking speed, and select walking-related outcomes in an exclusively ambulatory SCI sample. This study suggests the potential for non-task-specific aerobic exercise to improve walking following incomplete SCI and builds a foundation for further investigation aimed at the development of exercise based rehabilitation strategies to target functionally limiting impairments in ambulatory individuals with chronic SCI. PMID- 26666509 TI - Parents with a spinal cord injury. AB - STUDY DESIGN: This is a cross-sectional questionnaire. OBJECTIVES: The objective of this study was to describe the impact of parenting young children with a spinal cord injury (SCI) on various life situations (for example, personal, vocational and social). SETTING: Community; Denmark. METHODS: A postal survey was designed to collect data in persons with SCI regarding the following: (1) socio demographics, injury characteristics and parental status; (2) employment status; (3) environmental adjustments to support parenting roles; (4) childcare institution use and experiences; (5) network support for parenting; and (6) parenting advice for others. RESULTS: A total of 62 persons (58% men) responded to the survey, with 56% having paraplegia and 44% having tetraplegia. The majority of men (83%) and women (62%) were employed during the first 10 years of their child's lives. Half of the sample (50%) did not find the accessibility of their childcare institutions optimal to accommodate their SCI. Only 22% felt that they got answers about being a parent with an SCI. The main advice provided by the sample to those considering of becoming a parent was encouragement, whereas the advice for municipalities was to provide more funding support for personal assistance and aids. CONCLUSION: The present study provides insights into the challenges and satisfaction of being a parent post SCI across various life domains. Overall, the sample was very satisfied with their parenting role. The major issue noted for parents with SCI was the lack of support from local municipalities. PMID- 26666510 TI - Need and use of assistive devices for personal mobility by individuals with spinal cord injury. AB - OBJECTIVE: To investigate the provision, use, and unmet need of assistive devices for personal mobility in the Swiss population with spinal cord injury (SCI). DESIGN: Community survey 2012 of the Swiss Spinal Cord Injury Cohort Study. PARTICIPANTS: Individuals aged 16 or older with traumatic or non-traumatic SCI residing in Switzerland. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Provision, frequency of use, and unmet need (i.e. perceiving the need of a device but it not being provided) of 11 mobility devices were assessed by self-report and analyzed descriptively. Provision of devices was further analyzed by sex, age, SCI etiology, SCI severity, and time since SCI. RESULTS: Devices reported highest for provision (N = 492; mean age 55.3 +/- 15.1 years; 28.9% female) were adapted cars (78.2%) and manual wheelchairs (69.9%). Provision of various devices markedly varied with age and SCI severity (e.g. 34.6% of those aged 76+ had a walking frame compared to 3.1% of those aged 31-45; 50.0% of participants with complete tetraplegia had a power wheelchair compared to 7.6% of those with complete paraplegia). Many devices were mostly used daily (e.g. manual wheelchair) while others were mostly used less frequently (e.g. handbikes). Unmet need was highest for arm braces (53.2% of those in need) and power assisted wheelchairs (47.3%), and lowest for crutches (11.4%) and manual wheelchairs (4.8%). CONCLUSION: The devices individuals have or use is largely dependent on their age and SCI severity. While most participants have access to basic mobility devices, there is still a considerable degree of unmet need for certain devices. PMID- 26666511 TI - Expression and significance of CD44 and p-AKT in pancreatic head cancer. AB - BACKGROUND: CD44 and phosphorylated AKT (p-AKT) is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 and p-AKT has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 and p-AKT in pancreatic head cancer and their correlation with the prognosis of pancreatic head cancer patients. METHODS: Forty-eight pancreatic head cancer samples were collected dating from Jan. 2010 to Dec. 2012. Immunohistochemistry was applied to test the expression of CD44 and p-AKT in pancreatic head cancer. The clinical data of the patients were collected including their gender, age, the histology and location, lymph node metastasis, and so on. The correlation between the CD44 expression and the clinicopathological factors of patients with pancreatic head cancer was analyzed by the software SPSS 13.0. RESULTS: The positive rates of CD44 and p-AKT expression in the samples were 64.6 and 29.2 %, respectively. There was a significant difference between the CD44 expression and the pancreatic cancer' T staging, tumor node metastasis (TNM) staging, lymph node metastasis (P < 0.05). The Cox proportional hazard model showed that CD44 and lymph node metastasis were independent prognostic factors. CONCLUSIONS: CD44 was related to the distant metastasis and aggressive malignant behaviors of pancreatic head cancer. PMID- 26666512 TI - 4f fine-structure levels as the dominant error in the electronic structures of binary lanthanide oxides. AB - The ground-state 4f fine-structure levels in the intrinsic optical transition gaps between the 2p and 5d orbitals of lanthanide sesquioxides (Ln2 O3 , Ln = La...Lu) were calculated by a two-way crossover search for the U parameters for DFT + U calculations. The original 4f-shell potential perturbation in the linear response method were reformulated within the constraint volume of the given solids. The band structures were also calculated. This method yields nearly constant optical transition gaps between Ln-5d and O-2p orbitals, with magnitudes of 5.3 to 5.5 eV. This result verifies that the error in the band structure calculations for Ln2 O3 is dominated by the inaccuracies in the predicted 4f levels in the 2p-5d transition gaps, which strongly and non-linearly depend on the on-site Hubbard U. The relationship between the 4f occupancies and Hubbard U is non-monotonic and is entirely different from that for materials with 3d or 4d orbitals, such as transition metal oxides. This new linear response DFT + U method can provide a simpler understanding of the electronic structure of Ln2 O3 and enables a quick examination of the electronic structures of lanthanide solids before hybrid functional or GW calculations. PMID- 26666513 TI - Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure. AB - BACKGROUND: Proteoglycan 4 (PRG4) and hyaluronan (HA) are key synovial fluid constituents that contribute synergistically to cartilage boundary lubrication; however, the effects of their concentrations as well as their structure, both of which can be altered in osteoarthritis, on this functional synergism are unknown. The objectives of this study were to evaluate cartilage boundary lubricating ability of 1) PRG4 + HA in solution at constant HA concentration in a range of PRG4 concentrations, 2) constant PRG4 concentration in a range of HA concentrations, 3) HA + reduced/alkylated (R/A) PRG4, and 4) hylan G-F 20 + PRG4. METHODS: Static and kinetic friction coefficients (MU(static,Neq), ) were measured using a previously characterized cartilage cartilage boundary mode friction test for the following concentrations of purified PRG4 and HA: Test 1: HA (1.5 MDa, 3.3 mg/mL) + PRG4 from 4.5 - 1500 MUg/mL; Test 2: PRG4 (450, 150, 45 MUg/mL) + HA (1.5 MDa) from 0.3 - 3.3 mg/mL. Test 3: hylan G-F 20 (3. 3 mg/mL) + PRG4 (450 MUg/mL). Test 4: HA (3.3 mg/mL) + R/A PRG4 (450 MUg/mL). ANOVA was used to compare lubricants within (comparing 6 lubricants of interest) and between (comparing 3 lubricants of interest) test sequences, with Tukey and Fishers post-hoc testing respectively. RESULTS: This study demonstrates that both PRG4 and HA concentration, as well as PRG4 disulfide bonded structure, can alter the cartilage boundary lubricating ability of PRG4 + HA solutions. The boundary lubricating ability of high MW HA + PRG4 solutions was limited by very low concentrations of PRG4. Decreased concentrations of high MW HA also limited the cartilage boundary lubricating ability of HA + PRG4 solutions, with the effect exacerbated by low PRG4 concentrations. The reduction of friction by addition of PRG4 to a cross-linked HA viscosupplement product, but not with addition of R/A PRG4 to HA, is consistent with a non-covalent mechanism of interaction where tertiary and quaternary PRG4 structure are important. CONCLUSIONS: Collectively, these results demonstrate that deficiency of either or both PRG4 and HA, or alterations in PRG4 structure, may be detrimental to SF cartilage boundary lubricating function. This study provides further insight into the nature of cartilage boundary lubrication and advancement towards potential formulation of new intra-articular biotherapeutic treatments for osteoarthritis using PRG4 +/- HA. PMID- 26666514 TI - 2015 ACC/AHA Focused Update of Secondary Prevention Lipid Performance Measures: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. PMID- 26666515 TI - Organizational factors related to the confidence of workers in working with residents with dementia or depression in aged care facilities. AB - OBJECTIVES: There has been limited research examining how organizational factors are associated with the level of confidence of residential aged care staff in managing both residents' depression and the behavioural and psychological symptoms of residents with dementia (BPSD). This study investigated this issue. METHOD: A cross-sectional study design was employed. In total, 255 aged care staff (131 senior staff, 124 junior staff) from 21 residential care facilities participated in the study. All staff completed measures of self-efficacy in managing BPSD as well as confidence in working with older people with depression. They also completed measures of organizational climate (autonomy, cohesion, trust, pressure, support, recognition, fairness and encouragement of innovation) and measures of workplace experience (job role, number of years working in aged care facilities), job stress and satisfaction, and knowledge of depression. RESULTS: The results demonstrated that autonomy, trust, support, and job stress were associated with confidence in managing BPSD, while the factors related to confidence in managing depression were autonomy, support, job stress, job satisfaction, and knowledge of depression. CONCLUSION: These findings highlight that organizational climate factors need to be addressed in order to increase staff confidence in managing BPSD and depression. In particular, the findings demonstrate the importance of fostering organizational environments in which autonomy is promoted and there is support and cooperation among aged care staff. Attention to these factors is likely to increase the confidence of staff as they carry out their carer role. PMID- 26666516 TI - Modified in situ antimicrobial susceptibility testing method based on cyanobacteria chlorophyll a fluorescence. AB - The chlorophyll a fluorescence based antimicrobial susceptibility testing (AST) method presented in a previous work was based on the measurement of Chl a fluorescence of the gram(-) cyanobacterium Synechococcus sp. PCC 7942. Synechococcus sp. PCC 7942 as a gram(-) bacterium is affected by antibacterial agents via mechanisms affecting all gram(-) bacteria, however, as an exclusively phototrophic organism it would also be affected by photosynthesis inhibitory action of an agent that otherwise has no antibacterial properties. In this report, the method is modified by replacing the exclusively phototrophic Synechococcus sp. PCC 7942 with the Synechocystis sp. PCC 6714, capable of both phototrophic and heterotrophic growth in order to add versatility and better reflect the antibacterial effects of surfaces under study towards nonphotosynthetic bacteria. PMID- 26666518 TI - Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3. AB - BACKGROUND/AIMS: Janus kinase 3 (JAK3), a kinase mainly expressed in hematopoietic cells, has been shown to down-regulate the Na+/K+ ATPase and participate in the regulation of several ion channels and carriers. Channels expressed in thymus and regulating the abundance of T lymphocytes include the voltage gated K+ channel KCNE1/KCNQ1. The present study explored whether JAK3 contributes to the regulation of KCNE1/KCNQ1. METHODS: cRNA encoding KCNE1/KCNQ1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive K851AJAK3. Voltage gated K+ channel activity was measured utilizing two electrode voltage clamp. RESULTS: KCNE1/KCNQ1 activity was significantly increased by wild-type JAK3 and A568VJAK3, but not by K851AJAK3. The difference between oocytes expressing KCNE1/KCNQ1 alone and oocytes expressing KCNE1/KCNQ1 with A568VJAK3 was virtually abrogated by JAK3 inhibitor WHI-P154 (22 uM) but not by inhibition of transcription with actinomycin D (50 nM). Inhibition of KCNE1/KCNQ1 protein insertion into the cell membrane by brefeldin A (5 uM) resulted in a decline of the voltage gated current, which was similar in the absence and presence of A568VJAK3, suggesting that A568VJAK3 did not accelerate KCNE1/KCNQ1 protein retrieval from the cell membrane. CONCLUSION: JAK3 contributes to the regulation of membrane KCNE1/KCNQ1 activity, an effect sensitive to JAK3 inhibitor WHI-P154. PMID- 26666517 TI - Whole-transcriptome gene expression profiling in an epidermolysis bullosa simplex Dowling-Meara model keratinocyte cell line uncovered novel, potential therapeutic targets and affected pathways. AB - BACKGROUND: To be able to develop effective therapeutics for epidermolysis bullosa simplex (EBS), it is necessary to elucidate the molecular pathomechanisms that give rise to the disease's characteristic severe skin-blistering phenotype. RESULTS: Starting with a whole-transcriptome microarray analysis of an EBS Dowling-Meara model cell line (KEB7), we identified 207 genes showing differential expression relative to control keratinocytes. A complementary qRT PCR study of 156 candidates confirmed 76.58 % of the selected genes to be significantly up-regulated or down-regulated (p-value <0.05) within biological replicates. Our hit list contains previously identified genes involved in epithelial cell proliferation, cell-substrate adhesion, and responses to diverse biological stimuli. In addition, we identified novel candidate genes and potential affected pathways not previously considered as relevant to EBS pathology. CONCLUSIONS: Our results broaden our understanding of the molecular processes dysregulated in EBS. PMID- 26666519 TI - Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo controlled trial. AB - OBJECTIVE: Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. RESULTS: At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2.7 +/- 1.5 vs +0.1 +/- 1.8 kg, P < 0.001), BMI (-1.1 +/- 0.6 vs +0.1 +/- 0.7 kg/m(2) , P < 0.001), waist circumference (WC) (-2.0 +/- 1.3 vs -0.3 +/- 2.0 cm, P < 0.001) and hip circumference (HC) (-2.5 +/- 1.5 vs -0.3 +/- 1.8 cm, P < 0.001) compared with placebo. In addition, compared with placebo, carnitine administration in women with PCOS led to a significant reduction in fasting plasma glucose (-0.38 +/- 0.36 vs +0.11 +/- 0.97 mmol/l, P = 0.01), serum insulin levels (-14.39 +/- 25.80 vs +3.01 +/- 37.25 pmol/l, P = 0.04), homoeostasis model of assessment-insulin resistance (-0.61 +/- 1.03 vs +0.11 +/- 1.43, P = 0.04) and dehydroepiandrosterone sulphate (-3.64 +/- 7.00 vs -0.59 +/- 3.20 MUmol/l, P = 0.03). CONCLUSIONS: Overall, 12 weeks of carnitine administration in PCOS women resulted in reductions in weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone. PMID- 26666520 TI - In vitro evaluation of thio-poly acrylic acid for intraoral delivery. AB - CONTEXT: Intraoral drug delivery as mucosal delivery pathway provides a huge platform in the pharmaceutical field. OBJECTIVE: Combining mucoadhesiveness and controlled release of thio-poly acrylic acid as advanced excipient for buccal drug delivery. MATERIALS AND METHODS: Mediated by carbodiimide, cysteine was covalently attached to poly acrylic acid. This thiomer was assessed with regard to cytotoxicity, stability, mucoadhesion, and rheology as well as release behavior of Lidocaine. RESULTS: Stability assays of thio-poly acrylic acid were complying with United States Pharmacopeia requirements. Mucoadhesion assay such as tensile (total work of adhesion), bioadhesion, rotating cylinder revealed as this thiomer was superior in comparison to non-thiolated poly acrylic acid with 7.61-fold, 2.8-fold, 5.61-fold improvement, respectively without any toxic effect. The cell viability exhibited over 90% after incubation time of 3 h and 24 h respectively. Lidocaine release showed 1.98-fold more controlled release over 3 h in comparison to unmodified poly acrylic acid. CONCLUSION: Taken the findings in consideration, thio-poly acrylic acid provides excellent stability, controlled release, and superior mucoadhesive features. The prolonged residence time of thio poly acrylic acid represents a pillar in the buccal drug delivery. PMID- 26666521 TI - "We Always Think You're Here Permanently": The Paradox of "Permanent" Housing and Other Barriers to Recovery-Oriented Practice in Supportive Housing Services. AB - This qualitative study examines the views and practices of frontline providers working in supportive housing for adults with serious mental illness and how frontline workers understand their work as it relates to consumer mental health recovery. Utilizing 84 interviews with providers (N = 35) and 106 hours of observation of provider practice, a grounded theory of frontline practice in supportive housing is provided. Analyses revealed distinct differences between providers working within transitional versus permanent housing programs in their orientation to recovery. Implications for the design of the supportive housing continuum of care are discussed. PMID- 26666522 TI - Effect of Adipocyte Secretome in Melanoma Progression and Vasculogenic Mimicry. AB - Obesity, favored by the modern lifestyle, acquired epidemic proportions nowadays. Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades. Obesity involvement in melanoma aetiology has been recognized, but the implicated mechanisms remain unclear. In the present study, we address this relationship and investigate the influence of adipocytes secretome on B16-F10 and MeWo melanoma cell lines. Using the 3T3-L1 adipocyte cell line, as well as ex vivo subcutaneous (SAT) and visceral (VAT) adipose tissue conditioned medium, we were able to show that adipocyte-released factors play a dual role in increasing melanoma cell overall survival, both by enhancing proliferation and decreasing apoptosis. B16-F10 cell migration and cell-cell and cell-matrix adhesion capacity were predominantly enhanced in the presence of SAT and VAT released factors. Melanocytes morphology and melanin content were also altered by exposure to adipocyte conditioned medium disclosing a more dedifferentiated phenotype of melanocytes. In addition, exposure to adipocyte-secreted molecules induced melanocytes to rearrange, on 3D cultures, into vessel-like structures, and generate characteristic vasculogenic mimicry patterns. These findings are corroborated by the released factors profile of 3T3-L1, SAT, and VAT assessed by microarrays, and led us to highlight the mechanisms by which adipose secretome from sub-cutaneous or visceral depots promote melanoma progression. J. Cell. Biochem. 117: 1697-1706, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26666523 TI - Work of Breathing into Snow in the Presence versus Absence of an Artificial Air Pocket Affects Hypoxia and Hypercapnia of a Victim Covered with Avalanche Snow: A Randomized Double Blind Crossover Study. AB - Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase "AP"--breathing into the snow with a one liter air pocket, and phase "NP"--breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO2 and EtCO2) and peripheral oxygen saturation (SpO2) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for FIO2) or never (for FICO2). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing. PMID- 26666525 TI - Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3. AB - BACKGROUND: The creatine transporter CreaT (SLC6A8), a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. METHODS: CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568V JAK3 and inactive K851A JAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. RESULTS: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851A JAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 uM). CONCLUSION: JAK3 is a powerful negative regulator of the creatine transporter CreaT. PMID- 26666524 TI - OnabotulinumtoxinA Treatment for Overactive Bladder in the Elderly: Practical Points and Future Prospects. AB - Overactive bladder (OAB) increases with age. OAB in the elderly may be associated with increased risks of falls, fractures and mortality. Degeneration of the central nervous system in the elderly is proposed as one of the pathogenic factors for OAB. Recently, onabotulinumtoxinA (BoNT-A) 100 U has been demonstrated to be well tolerated, and it significantly improves all OAB symptoms and health-related quality of life in patients who are inadequately managed with anticholinergics. However, an increased risk of a large post-void residual volume and a lower long-term success rate were noted in frail elderly patients. Careful patient selection for BoNT-A injection treatment is important in elderly OAB patients. Patients who are frail, are elderly, have comorbidity or have a post void residual volume >100 mL should be monitored carefully after BoNT-A injection treatment to prevent urinary retention and subsequent urinary tract infection. Use of liposomes to carry BoNT-A across the urothelial barrier decreases urgency frequency episodes without compromising detrusor contractility and might avoid urinary tract infection. This treatment might prevent undesired detrusor underactivity after BoNT-A injection treatment, especially in elderly patients who have low detrusor contractility. For treatment of OAB in the elderly, clinicians should be aware of the balance between therapeutic efficacy and safety. PMID- 26666527 TI - Hunt promises to investigate claims of mental health trust's failure over unexpected deaths. PMID- 26666526 TI - Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data. AB - BACKGROUND: The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse. METHODS: We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up. RESULTS: Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause specific mortality, compared to low D-ROM levels (<= 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15 1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22 2.24). CONCLUSIONS: In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality. PMID- 26666528 TI - Evaluation of an Automated Chemiluminescent Immunoassay in Typing Detection of IgG Antibodies Against Herpes Simplex Virus. AB - BACKGROUD: Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common infectious agents worldwide and the primary infection of HSV remains a major problem in the pregnant women in China nowadays. At present, typing detection of HSV is mainly based on ELISA in China. METHODS: In this study, we evaluated the performance of a newly introduced chemiluminescent immunoassay assay (CLIA) for the determination of serum HSV-1 and HSV-2 immunoglobulin G (IgG) antibodies. RESULTS: The functional sensitivity of detecting HSV-1 and HSV-2 IgG were 0.7 Index and 0.6 Index, respectively. The repeatability and the total imprecision coefficient of variations were both below 10%, and the recoveries of these assays ranged from 90% to 110%. High concentration of hemoglobin, lipids, and bilirubin in samples did not affect the results. The infective rates of HSV-1 and HSV-2 were 919 (87.5%) and 169 (16.1%), respectively. HSV-1 seroprevalence was significantly higher than that of HSV-2 (P < 0.001). CONCLUSION: CLIA is an excellent method for HSV-1 and HSV-2 IgG measurement and can be used as a routine screening test. The infective rate of HSV was pretty high among women before pregnancy or in the period of pregnancy in Beijing. PMID- 26666529 TI - Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant-like effects. AB - Galanin (GAL) and the NPYY1 agonist play a role in mood regulation and both neuropeptides interact in several central functions. The present study examined the interaction between Galanin receptor 2 (GALR2) and Neuropeptide Y Y1 receptor (NPYY1R) in the dentate gyrus (DG) of the Hippocampus in relation to depression like behavior. Using receptor autoradiography, in situ hybridization and in situ proximity ligation assay an interaction between GALR and NPYY1R was demonstrated in the DG probably involving the formation of GALR2-NPYY1R heteroreceptor complexes. These complexes were specifically observed in the polymorphic and subgranular subregions of the DG, where both receptors were found to colocalize. Moreover, this GALR2/NPYY1R interaction was linked to an enhancement of the antidepressive-like behavior mediated by NPYY1R in the forced swimming test. Specific cells populations within DG subregions may be involved in this behavioral effect since the coactivation of GALR2 and NPYY1R enhances the NPYY1R mediated reduction in the number of c-Fos immunoreactive nuclei in the polymorphic region. These results indicate that GALR2/NPYY1R interactions can provide a novel integrative mechanism in DG in depression-related behavior and may give the basis for the development of drugs targeting GALR2/NPYY1R heteroreceptor complexes in the DG of the hippocampus for the treatment of depression. PMID- 26666530 TI - Genetic sex and the volumes of the caudate-putamen, nucleus accumbens core and shell: original data and a review. AB - Sex differences are widespread across vertebrate nervous systems. Such differences are sometimes reflected in the neural substrate via neuroanatomical differences in brain region volume. One brain region that displays sex differences in its associated functions and pathologies is the striatum, including the caudate-putamen (dorsal striatum), nucleus accumbens core and shell (ventral striatum). The extent to which these differences can be attributed to alterations in volume is unclear. We thus tested whether the volumes of the caudate-putamen, nucleus accumbens core, and nucleus accumbens shell differed by region, sex, and hemisphere in adult Sprague-Dawley rats. As a positive control for detecting sex differences in brain region volume, we measured the sexually dimorphic nucleus of the medial preoptic area (SDN-POA). As expected, SDN-POA volume was larger in males than in females. No sex differences were detected in the volumes of the caudate-putamen, nucleus accumbens core or shell. Nucleus accumbens core volume was larger in the right than left hemisphere across males and females. These findings complement previous reports of lateralized nucleus accumbens volume in humans, and suggest that this may possibly be driven via hemispheric differences in nucleus accumbens core volume. In contrast, striatal sex differences seem to be mediated by factors other than striatal region volume. This conclusion is presented within the context of a detailed review of studies addressing sex differences and similarities in striatal neuroanatomy. PMID- 26666531 TI - Callosotopy: leg motor connections illustrated by fiber dissection. AB - Precise anatomical knowledge of the structure of the corpus callosum is important in split-brain research and during neurosurgical procedures sectioning the callosum. According to the classic literature, commissural fibers connecting the motor cortex are situated in the anterior part of the corpus callosum. On the other hand, more recent imaging studies using diffusion tensor imaging indicate a more posterior topography of callosal fibers connecting motor areas. Topographical knowledge is especially critical when performing disconnective callosotomies in epilepsy patients who experience sudden loss of leg motor control, so-called epileptic drop attacks. In the current study, we aim to precisely delineate the topography of the leg motor connections of the corpus callosum. Of 20 hemispheres obtained at autopsy, 16 were dissected according to Klingler's fiber dissection technique to study the course and topography of callosal fibers connecting the most medial part of the precentral gyrus. Fibers originating from the anterior bank of the central sulcus were invariably found to be located in the isthmus of the corpus callosum, and no leg motor fibers were found in the anterior part of the callosum. The current results suggest that the disconnection of the pre-splenial fibers, located in the posterior one-third of the corpus callosum, is paramount in obtaining a good outcome after callosotomy. PMID- 26666533 TI - Ecological change predicts population dynamics and genetic diversity over 120 000 years. AB - While ecological effects on short-term population dynamics are well understood, their effects over millennia are difficult to demonstrate and convincing evidence is scant. Using coalescent methods, we analysed past population dynamics of three lizard species (Psammodromus hispanicus, P. edwardsianus, P. occidentalis) and linked the results with climate change data covering the same temporal horizon (120 000 years). An increase in population size over time was observed in two species, and in P. occidentalis, no change was observed. Temporal changes in temperature seasonality and the maximum temperature of the warmest month were congruent with changes in population dynamics observed for the three species and both variables affected population density, either directly or indirectly (via a life-history trait). These results constitute the first solid link between ecological change and long-term population dynamics. The results moreover suggest that ecological change leaves genetic signatures that can be retrospectively traced, providing evidence that ecological change is a crucial driver of genetic diversity and speciation. PMID- 26666534 TI - A T cell lymphoblastic lymphoma with mucormycosis as unusual etiology of acute cerebral ischemia. PMID- 26666532 TI - IRES-dependent translated genes in fungi: computational prediction, phylogenetic conservation and functional association. AB - BACKGROUND: The initiation of translation via cellular internal ribosome entry sites plays an important role in the stress response and certain physiological conditions in which canonical cap-dependent translation initiation is compromised. Currently, only a limited number of these regulatory elements have been experimentally identified. Notably, cellular internal ribosome entry sites lack conservation of both the primary sequence and mRNA secondary structure, rendering their identification difficult. Despite their biological importance, the currently available computational strategies to predict them have had limited success. We developed a bioinformatic method based on a support vector machine for the prediction of internal ribosome entry sites in fungi using the 5'-UTR sequences of 20 non-redundant fungal organisms. Additionally, we performed a comparative analysis and characterization of the functional relationships among the gene products predicted to be translated by this cap-independent mechanism. RESULTS: Using our method, we predicted 6,532 internal ribosome entry sites in 20 non-redundant fungal organisms. Some orthologous groups were enriched with our positive predictions. This is the case of the HSP70 chaperone family, which remarkably has two verified internal ribosome entry sites, one in humans and the other in flies. A second example is the orthologous group of the eIF4G repression protein Sbp1p, which has two homologous genes known to be translated by this cap independent mechanism, one in mice and the other in yeast. These examples emphasize the wide conservation of these regulatory elements as a result of selective pressure. In addition, we performed a protein-protein interaction network characterization of the gene products of our positive predictions using Saccharomyces cerevisiae as a model, which revealed a highly connected and modular topology, suggesting a functional association. A remarkable example of this functional association is our prediction of internal ribosome entry sites elements in three components of the RNA polymerase II mediator complex. CONCLUSIONS: We developed a method for the prediction of cellular internal ribosome entry sites that may guide experimental and bioinformatic analyses to increase our understanding of protein translation regulation. Our analysis suggests that fungi show evolutionary conservation and functional association of proteins translated by this cap-independent mechanism. PMID- 26666535 TI - Dysregulation of ferroportin gene expression in beta(0)-thalassemia/Hb E disease. AB - During erythropoiesis, iron levels need to be carefully regulated to ensure there is sufficient iron available for hemoglobin synthesis, but that there is no excess to cause damage to the developing erythroblast. Iron influx to the developing erythroblast is controlled by the expression of the transferrin receptor, while iron efflux is regulated by ferroportin (FPN), the sole iron exporting protein. FPN is encoded through multiple messenger RNAs (mRNAs) some of which contain an iron-responsive element (variant I mRNAs) and some of which do not (variant II mRNAs). This study sought to investigate the expression of the FPN mRNAs in developing erythroblasts from normal controls and beta(0) thalassemia/Hb E patients. While levels of FPN protein were relatively constant, marked reductions of the variant I message were seen in erythroblasts from beta(0)-thalassemia/Hb E patients as compared to normal control cells, particularly in late erythropoiesis. Variant II mRNAs were generally increased during erythroid differentiation. No difference was seen in levels of either transferrin or ferritin heavy chain expression. While no difference was observed in labile iron pools under normal culture conditions, erythroblasts from beta(0) thalassemia/Hb E patients showed a significantly reduced expression of total FPN message under high iron conditions as compared to normal control erythroblasts. These results are consisted with dysregulation of iron efflux from the maturing erythroblast in beta(0)-thalassemia/Hb E patients, and this dysregulation possibly contributes to ineffective erythropoiesis seen in these patients. PMID- 26666536 TI - Refractory acute lymphoblastic leukemia in Chinese children: bridging to stem cell transplantation with clofarabine, cyclophosphamide and etoposide. AB - Refractory or relapsed acute lymphoblastic leukemia (r/r ALL) represents the leading cause of cancer mortality in children. Clofarabine is effective in inducing remission thus enabling bridging to hematopoietic stem cell transplantation (HSCT). We report the results in treating Hong Kong Chinese pediatric patients with r/rALL by clofarabine/cyclophosphamide/etoposide (CLO 218) combination therapy. A retrospective review of patients treated between January 2009 and December 2014 in the two tertiary referral pediatric oncology units in Hong Kong. Thirteen patients were identified. All were Chinese and seven were male. Median age at clofarabine treatment was 8 years and the median duration of follow-up was 10 months. Nine patients had B-ALL and four had T-ALL. All were refractory to the preceding regimen(s). The median number of prior treatment regimens was 2; two patients had previous HSCT. Complete remission (CR) was achieved in five patients, Complete remission with incomplete counts (CRi) in two, PR in two, and non-remission (NR) in two. All four patients with T-ALL responded with three patients achieving CR. Eight out of nine patients who responded could be bridged to HSCT. Among those who were transplanted, four remained alive and in remission, three relapsed post-HSCT, and one died from transplant-related mortality. Treatment toxicities were common including febrile neutropenia in all subjects and culture-proven bacteremia in five patients. Hepatotoxicity was mild and reversible with no case of veno-occlusive disease. The clofarabine-based regimen is a promising strategy to induce disease remission in r/rALL and bridge to HSCT. Septic complications are, however, frequent necessitating prompt management with adequate supportive care in specialized centers. PMID- 26666537 TI - Management of chronic refractory cough. AB - Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise. PMID- 26666540 TI - Population mixing and childhood leukaemia. PMID- 26666538 TI - Registering prostate external beam radiotherapy with a boost from high-dose-rate brachytherapy: a comparative evaluation of deformable registration algorithms. AB - BACKGROUND: Registering CTs for patients receiving external beam radiotherapy (EBRT) with a boost dose from high-dose-rate brachytherapy (HDR) can be challenging due to considerable image discrepancies (e.g. rectal fillings, HDR needles, HDR artefacts and HDR rectal packing materials). This study is the first to comparatively evaluate image processing and registration methods used to register the rectums in EBRT and HDR CTs of prostate cancer patients. The focus is on the rectum due to planned future analysis of rectal dose-volume response. METHODS: For 64 patients, the EBRT CT was retrospectively registered to the HDR CT with rigid registration and non-rigid registration methods in VelocityAI. Image processing was undertaken on the HDR CT and the rigidly-registered EBRT CT to reduce the impact of discriminating features on alternative non-rigid registration methods applied in the software suite for Deformable Image Registration and Adaptive Radiotherapy Research (DIRART) using the Horn-Schunck optical flow and Demons algorithms. The propagated EBRT-rectum structures were compared with the HDR structure using the Dice similarity coefficient (DSC), Hausdorff distance (HD) and average surface distance (ASD). The image similarity was compared using mutual information (MI) and root mean squared error (MSE). The displacement vector field was assessed via the Jacobian determinant (JAC). The post-registration alignments of rectums for 21 patients were visually assessed. RESULTS: The greatest improvement in the median DSC relative to the rigid registration result was 35 % for the Horn-Schunck algorithm with image processing. This algorithm also provided the best ASD results. The VelocityAI algorithms provided superior HD, MI, MSE and JAC results. The visual assessment indicated that the rigid plus deformable multi-pass method within VelocityAI resulted in the best rectum alignment. CONCLUSIONS: The DSC, ASD and HD improved significantly relative to the rigid registration result if image processing was applied prior to DIRART non-rigid registrations, whereas VelocityAI without image processing provided significant improvements. Reliance on a single rectum structure-correspondence metric would have been misleading as the metrics were inconsistent with one another and visual assessments. It was important to calculate metrics for a restricted region covering the organ of interest. Overall, VelocityAI generated the best registrations for the rectum according to the visual assessment, HD, MI, MSE and JAC results. PMID- 26666543 TI - Carbon monoxide exposure may underlie the increased leukaemia risk in children living next to motor highways. PMID- 26666542 TI - The authors' reply: Population mixing and childhood leukaemia. PMID- 26666541 TI - Body mass index, gestational weight gain and fatty acid concentrations during pregnancy: the Generation R Study. AB - Obesity during pregnancy may be correlated with an adverse nutritional status affecting pregnancy and offspring outcomes. We examined the associations of prepregnancy body mass index and gestational weight gain with plasma fatty acid concentrations in mid-pregnancy. This study was embedded in a population-based prospective cohort study among 5636 women. We obtained prepregnancy body mass index and maximum weight gain during pregnancy by questionnaires. We measured concentrations of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 polyunsaturated fatty acid (n-3 PUFA) and n-6 polyunsaturated fatty acid (n-6 PUFA) at a median gestational age of 20.5 (95% range 17.1-24.9) weeks. We used multivariate linear regression models. As compared to normal weight women, obese women had higher total SFA concentrations [difference: 0.10 standard deviation (SD) (95% Confidence Interval (CI) 0, 0.19)] and lower total n-3 PUFA concentrations [difference: - 0.11 SD (95% CI - 0.20, - 0.02)]. As compared to women with sufficient gestational weight gain, those with excessive gestational weight gain had higher SFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.25)], MUFA concentrations [difference: 0.16 SD (95% CI 0.08, 0.24)] and n-6 PUFA concentrations [difference: 0.12 SD (95% CI 0.04, 0.21)]. These results were not materially affected by adjustment for maternal characteristics. Our results suggest that obesity and excessive weight gain during pregnancy are associated with an adverse fatty acids profile. Further studies are needed to assess causality and direction of the observed associations. PMID- 26666544 TI - Devastating Delayed Leukoencephalopathy Associated with Bath Salt Inhalation. AB - BACKGROUND: "Bath salts" or synthetic cathinone toxicity remains a potentially deadly clinical condition. We report a delayed leukoencephalopathy with persistent minimally conscious state. METHODS: Case report. RESULTS: A 36-year old man presents with delayed encephalopathy, dysautonomia, fulminant hepatic failure, and renal failure from severe rhabdomyolysis after consuming bath salts. MRI showed diffusion restriction in the splenium of the corpus callosum and subcortical white matter. CONCLUSIONS: The combination of acute leukoencephalopathy, rhabdomyolysis and fulminant hepatic failure may point to bath salt inhalation and should be known to neurointensivists. PMID- 26666545 TI - Thromboelastography After Murine TBI and Implications of Beta-Adrenergic Receptor Knockout. AB - BACKGROUND: The source of coagulopathy in traumatic brain injury (TBI) is multifactorial and may include adrenergic stimulation. The aim of this study was to assess coagulopathy after TBI using thromboelastography (TEG), and to investigate the implications of beta-adrenergic receptor knockout. METHODS: Adult male wild type c57/bl6 (WT) and beta1/beta2-adrenergic receptor knockout (BKO) mice were assigned to either TBI (WT-TBI, BKO-TBI) or sham injury (WT-sham, BKO sham). Mice assigned to TBI were subject to controlled cortical impact (CCI). At 24 h post-injury, whole blood samples were obtained and taken immediately for TEG. RESULTS: At 24 h after injury, a trend toward increased fibrinolysis was seen in WT-TBI compared to WT-sham although this did not reach significance (EPL 8.1 vs. 0 %, p = 0.18). No differences were noted in fibrinolysis in BKO-TBI compared to BKO-sham (LY30 2.6 vs. 2.5 %, p = 0.61; EPL 3.4 vs. 2.9 %, p = 0.61). In addition BKO-TBI demonstrated increased clot strength compared to BKO-sham (MA 76.6 vs. 68.6, p = 0.03; G 18.2 vs. 11.3, p = 0.03). CONCLUSIONS: In a mouse TBI model, WT mice sustaining TBI demonstrated a trend toward increased fibrinolysis at 24 h after injury while BKO mice did not. These findings suggest beta-blockade may attenuate the coagulopathy of TBI and minimize progression of intracranial hemorrhage by reducing fibrinolysis and increasing clot strength. PMID- 26666546 TI - Usability of Cryopreserved Aortic Allografts for Middle Hepatic Vein Reconstruction During Living-Donor Liver Transplantation. AB - Iliac vein allografts are suitable for middle hepatic vein (MHV) reconstruction during living-donor liver transplantation (LDLT), but their supply is often limited. Polytetrafluoroethylene (PTFE) grafts are easily available but have drawbacks of accidental gastric penetration and non-degradable foreign body. To replace the use of PTFE grafts, we started using cryopreserved aorta allografts (CAAs). This study presents the technical details and patency outcomes of using CAAs in MHV reconstruction. We reviewed the surgical techniques of CAA interposition and analyzed the patency rates in 74 patients who underwent LDLT during the 6-year study period. The two control groups received either cryopreserved iliac veins (n = 122) or PTFE grafts (n = 84). The surgical techniques for MHV reconstruction used to implant the CAA and PTFE grafts are very similar because the techniques developed for PTFE grafts were also applied to CAAs. We inserted an arterial patch at the liver cut surface because the CAA wall is too thick to perform direct anastomosis. Two patients (2.7 %) underwent MHV stenting during the first month. The 1-year patency rate was 69.7 % in the CAA group vs. 39.2 % in iliac vein group vs. 57.2 % in PTFE group (p = 0.000). The overall graft and patient survival rates did not differ depending on the MHV interposition vessel materials (p > 0.1). CAAs combined with small-artery patches demonstrated high patency rates that surpass other vessel grafts, and thus, we suggest that CAA can be reliably used for MHV reconstruction when CAA is available. PMID- 26666547 TI - Diagnosis and Treatment of Abdominal Arterial Bleeding After Radical Gastrectomy: a Retrospective Analysis of 1875 Consecutive Resections for Gastric Cancer. AB - BACKGROUND: Massive abdominal arterial bleeding is an uncommon yet life threatening complication of radical gastrectomy. The exact incidence and standardized management of this lethal morbidity are not known. METHODS: Between January 2003 and December 2013, data from 1875 patients undergoing radical gastrectomy with D2 or D2 plus lymphadenectomy were recorded in a prospectively designed database from a single institute. The clinical data and management of both early (within 24 h) and late (beyond 24 h) postoperative abdominal arterial hemorrhages were explored. For late bleeding patients, transcatheter arterial embolization (TAE) and re-laparotomy were compared to determine the better initial treatment option. RESULTS: The overall prevalence of postoperative abdominal arterial bleeding was 1.92 % (n = 36), and related mortality was 33.3 % (n = 12). Early and late postoperative bleedings were found in 6 and 30 patients, respectively. The onset of massive arterial bleeding occurred on average postoperative day 19. The common hepatic artery and its branches were the most common bleeding source (13/36; 36.1 %). All the early bleeding patients were treated with immediate re-laparotomy. For late bleeding, patients from the TAE group had a significantly lower mortality rate than that of the patients from the surgery group (7.69 vs. 56.25 %, respectively, P = 0.008) as well as a shorter procedure time for bleeding control (2.3 +/- 1.1 vs. 4.8 +/- 1.7 h, respectively, P < 0.001). Four rescue reoperations were performed for TAE failures; the salvage rate was 50 % (2/4). Ten patients developed massive re-bleeding after initial successful hemostasis by either TAE (5/13) or open surgery (5/16). Three out of the 10 re-bleeding patients died of disseminated intravascular coagulation (DIC), while the other 7 recovered eventually by repeated TAE and/or surgery. CONCLUSION: Abdominal arterial bleeding following radical gastrectomy tends to occur during the later phase after surgery, with further complications such as abdominal infection and fistula(s). For late bleeding, TAE can be considered as the first-line treatment when possible. PMID- 26666548 TI - Durable Flap-Valve Mitigation of Duodenogastric Reflux, Remnant Gastritis and Dumping Syndrome Following Billroth I Reconstruction. AB - BACKGROUND: We have reported the short-term results of pylorus reconstruction gastrectomy (PRG) that prevents duodenogastric reflux (DGR) and remnant gastritis after distal gastrectomy. We herein report the long-term results of the PRG. PATIENTS AND METHODS: PRG was performed in 37 patients (age 31 to 86 [mean 67.8 +/- 12.3] years, male:female = 22:15) with gastric cancer from June 2006 through December 2013. We examined the long-term outcome in 28 patients (age 41 to 86 [mean 67.0 +/- 10.7] years, male:female = 18:10) that passed over 3 years after surgery (LTR 44.1 +/- 11.7 months), and compared with their short-term result after the operation (STR 13.1 +/- 6.9 months). The adverse events of gastric surgery evaluated in this study consisted of the degree of remnant gastritis, the presence of dumping syndrome, and degree of weight loss (%). RESULTS: There was no difference in the degree of DGR and remnant gastritis by gastroscopic finding between LTR and STR after PRG (P = 0.21). Statistically, there was no difference in the bile acid concentration of remnant gastric juice between LTR and STR (108.4 +/- 254.1 vs. 94.0 +/- 208.6 MUmol/L, P = 0.33), and weight loss of LTR was the same as that of STR (5.67 +/- 7.08 vs. 4.59 +/- 5.63%, P = 0.34). There were few morphological changes in the reconstructed pylorus by the long-term course, but 2 patients showed mild atrophy. CONCLUSION: The form of reconstructed pylorus and the effect that reduces side effects of Billroth I seem to last for a long time. PMID- 26666550 TI - Case reports - When bronchial obstruction in the young adult is not asthma and inhalers do not help. AB - INTRODUCTION: Localised bronchial obstruction is a rare differential diagnosis to asthma. CASE STUDY: We describe two younger patients treated unsuccessfully for asthma and eventually diagnosed with localised bronchoconstriction. RESULTS: Bronchoscopy revealed bronchoconstriction: Tracheobronchomalacia in case 1 and fixed obstruction in case 2. CONCLUSION: A systematic approach to the asthma patient with absent response to therapy facilitates rational use of therapeutic and diagnostic resources. PMID- 26666549 TI - Coinfection of Pulmonary Hydatid Cyst and Aspergilloma: Case Report and Systematic Review. AB - Aspergilloma infection consists of a mass of fungal hyphae, inflammatory cells, fibrin, mucus, and tissue debris and can colonize lung cavities due to underlying diseases such as tuberculosis, sarcoidosis, bronchiectasis, cavitary lung cancer, neoplasms, ankylosing spondylitis, bronchial cysts, and pulmonary infarction. Here we report coinfection of pulmonary hydatid cyst and aspergilloma in a 34 year-old female who had had history of minor thalassemia and suffered from chest pain, dyspnea, non-productive cough for at least five months, and hemoptysis for 20 days. Radiographic sign showed a large cavitary lesion (5 * 6 * 6 cm) involving left lower lobe (LLL). Dichotomous septate hyphae were observed in bronchoalveolar lavage and biopsy specimens from LLL. The patient subsequently improved after combined anti-helminth therapies with albendazole (400 mg/bd) and lobectomy. According to morphological and molecular characterization, Aspergillus niger was confirmed. In vitro antifungal susceptibility tests revealed that the MIC values for the antifungals used in this case in increasing order were posaconazole (0.125 ug/ml), itraconazole and voriconazole (0.5 ug/ml), and amphotericin B (1 ug/ml). The minimum effective concentration for caspofungin was 0.125 ug/ml. Subsequently, we systematically reviewed 22 confirmed cases of pulmonary hydatid cyst and aspergilloma during a period of 19 years (1995-2014) and discussed the epidemiology, clinical features, and treatment of this disease. PMID- 26666551 TI - Ectopic expression of PgRab7 in rice plants (Oryza sativa L.) results in differential tolerance at the vegetative and seed setting stage during salinity and drought stress. AB - In this work, we have overexpressed a vesicle trafficking protein, Rab7, from a stress-tolerant plant, Pennisetum glaucum, in a high-yielding but stress sensitive rice variety Pusa Basmati-1 (PB-1). The transgenic rice plants were tested for tolerance against salinity and drought stress. The transgenic plants showed considerable tolerance at the vegetative stage against both salinity (200 mM NaCl) and drought stress (up to 12 days after withdrawing water). The protection against salt and drought stress may be by regulating Na+ ion homeostasis, as the transgenic plants showed altered expression of multiple transporter genes, including OsNHX1, OsNHX2, OsSOS1, OsVHA, and OsGLRs. In addition, decreased generation and maintenance of lesser reactive oxygen species (ROS), with maintenance of chloroplast grana and photosynthetic machinery was observed. When evaluated for reproductive growth, 89-96 % of seed setting was maintained in transgenic plants during drought stress; however, under salt stress, a 33-53 % decrease in seed setting was observed. These results indicate that PgRab7 overexpression in rice confers differential tolerance at the seed setting stage during salinity and drought stress and could be a favored target for raising drought-tolerant crops. PMID- 26666552 TI - Biochemistry and cell ultrastructure changes during senescence of Beta vulgaris L. leaf. AB - The comparative study of biochemical and ultrastructure features in senescing sugar beet (Beta vulgaris L.) leaves was carried out. One group of plants was grown under normal conditions in washed river sand and poured in turn with nitrate-containing mineral solution or water (N plants). Another group of plants, after 1 month of normal growth, was further grown with nitrate omitted in the nutritive solution (defN plants). The starting point of normal leaf senescence in N plants was identified by the maximal content of soluble protein. Soluble carbohydrate pools were statistically constant in senescing N plants, whereas glucose pools varied noticeably. A decrease in the contents of soluble protein and chlorophyll (a + b) in the course of senescing was typical for N plant leaves. The cell membrane in N plant leaves remained mostly intact; the central vacuoles in the leaf cells were large, and their membranes remained intact. The chloroplasts and mitochondria in senescing N plant leaves became swollen. The vesicles that were present in the cytoplasm of N plant leaves were especially large in the oldest leaves. It was concluded that senescing of sugar beet leaves at sufficient nitrate nutrition occurs according to a "vacuolar" scenario. In the case of nitrate deficiency, the content of soluble carbohydrates in defN leaves first reached maximum and then decreased in older leaves; the protein and chlorophyll (a + b) contents were totally lower than those in normal leaves and continuously decreased during the experiments. Chloroplasts in mesophyll cells of defN plant leaves became more rounded; starch grains in chloroplasts degraded and the number and size of lipid globules increased. The multitude of membrane impairments and lots of large vesicles-"crystals" appeared during the experiment. The results showed the controlling action of nitrogen nutrition in the senescing of sugar beet leaves. PMID- 26666554 TI - [Optical diagnostic methods for improving early tumor diagnosis in the upper aerodigestive tract]. PMID- 26666555 TI - [Recent developments in the diagnosis and treatment of obstructive sleep apnea]. AB - Over the past years, the diagnostic tools and therapeutic approaches for obstructive sleep apnea (OSA) have further evolved. Based on a review of current literature and the personal experiences of the authors, the most relevant developments are summarized in this article and discussed with regard to their impact on the clinical management of this disease. In the third edition of the "International Classification of Sleep Disorders", the classification of sleep disordered breathing was modified. Notably, additional clinical criteria for the diagnosis of OSA were established and out-of-center sleep testing was introduced as an alternative to polysomnography. Recent technical advancement of new diagnostic tools (e.g., peripheral arterial tonometry and pulse wave analysis) has further expanded the diagnostic possibilities. Drug-induced sleep endoscopy enables reliable assessment of the level and degree of upper airway obstruction. Whether this gain in diagnostic information leads to an improvement in surgical outcome is, however, still under discussion. The relevance of positional OSA has received increasing attention-the proportion of patients in whom sleeping position significantly impacts disease is reported to be above 50%. For these patients, the introduction of the sleep position trainer has made a new therapeutic option available. Furthermore, hypoglossal nerve stimulation (upper airway stimulation) has substantially expanded the surgical spectrum of OSA treatment. For the established surgical treatment options, randomized trials with superior methodology have been published, particularly for bimaxillary advancement and tonsillectomy with uvulopalatopharyngoplasty. These developments are of particular interest for the otolaryngologist and will influence daily practice. PMID- 26666556 TI - [Noninvasive imaging using autofluorescence endoscopy: Value for the early detection of laryngeal cancer]. AB - BACKGROUND: Autofluorescence endoscopy is able to delineate malignancy from normal tissue by color change. The objective of the present study was to assess the value of this noninvasive imaging method for the early detection of laryngeal cancer and its precursor lesions. PATIENTS AND METHODS: In a prospective study, 152 patients with a laryngeal lesion who were undergoing microlaryngoscopy were investigated. Autofluorescence endoscopy was performed after conventional white light endoscopy, just before excisional biopsy was carried out for histologic verification. RESULTS: In the early detection of laryngeal cancer and its precursor lesions, autofluorescence endoscopy showed a significantly higher sensitivity (98 vs. 88%) and accuracy (97 vs. 90%) than white light endoscopy alone, whereas the specificity (97 vs. 93%) was essentially equal in both methods. CONCLUSION: Autofluorescence endoscopy qualifies as a simple screening procedure for rapid detection of suspicious lesions and assessment of their horizontal extension. This allows for guided biopsy or tumor resection, and can also be used in oncological follow-up. PMID- 26666557 TI - [Optical coherence tomography for early diagnosis of epithelial dysplasia and microinvasive carcinoma of the upper aerodigestive tract]. AB - BACKGROUND: Gold standard in the evaluation of upper aerodigestive tract (UADT) lesions is white light endoscopy followed by invasive tissue biopsy. This procedure is time consuming and expensive. Optical coherence tomography (OCT) is a noninvasive method, which provides high resolution, cross-sectional images of superficial tissue layers in real time. OBJECTIVE: This article aims to present a contemporary and comprehensive review on the role of OCT in differentiating between epithelial dysplasias and early invasive carcinomas of the UADT. MATERIALS AND METHODS: PubMed was searched using "optical coherence tomography/larynx" and other appropriate search strings in August 2015. RESULTS: OCT enables differentiation between benign, premalignant, and early malignant lesions of the UADT with high sensitivity and specificity. In addition, OCT holds promise as a clinical tool for guidance of surgical biopsies, follow-up of recurrent lesions, and for demarcation of tumor margins. Inadequate evidence and technical limitations hamper implementation of OCT into clinical routine. CONCLUSION: If the aforementioned problems are successfully solved, OCT seems to have the potential to substantially improve both diagnosis and management of precancerous and early cancerous lesions of the UADT. PMID- 26666558 TI - [Optical diagnostic methods for early tumour diagnosis in the upper aerodigestive tract: Quo vadis?]. AB - BACKGROUND: Optical diagnostic methods may simplify and improve the early diagnosis of tumours of the upper aerodigestive tract; however, these have not yet found their way into clinical routine. OBJECTIVE: This article aims to define the problems that have prevented routine use of optical diagnostic methods so far, as well as listing and also explaining potential trendsetting approaches to overcome these difficulties. MATERIALS AND METHODS: The study is based on a combined analysis of publically accessible databases (PubMed MEDLINE, Thompson Reuters Web of Science, SPIE. Digital Library; full time period available; search strings: "oral cavity", "pharynx", "larnyx", "optical diagnosis", "optical biopsy", "optical coherence tomography", "confocal endomicroscopy", "fluorescence endoscopy", "narrow band imaging", "non-linear imaging", "fluorescence lifetime imaging"), as well as personal experiences. RESULTS: Both conceptual and methodical problems were determined, and possible solutions based on current developments are discussed. CONCLUSION: Optical diagnostic methods have the potential to revolutionise early diagnosis of upper aerodigestive tract malignancies, providing the different hurdles listed in this review can be overcome. PMID- 26666559 TI - A Comparison of Postelimination Measles Epidemiology in the United States, 2009 2014 Versus 2001-2008. AB - Background: Measles, a vaccine-preventable disease that can cause severe complications, was declared eliminated from the United States in 2000. The last published summary of US measles epidemiology was during 2001-2008. We summarized US measles epidemiology during 2009-2014. Methods: We compared demographic, vaccination, and virologic data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2009-December 31, 2014 and January 1, 2001-December 31, 2008. Results: During 2009-2014, 1264 confirmed measles cases were reported in the United States, including 275 importations from 58 countries and 66 outbreaks. The annual median number of cases and outbreaks during this period was 130 (range, 55-667 cases) and 10 (range, 4-23 outbreaks), respectively, compared with an annual median of 56 cases (P = .08) and 4 outbreaks during 2001-2008 (P = .04). Among US-resident case patients during 2009-2014, children aged 12-15 months had the highest measles incidence (65 cases; 8.3 cases/million person-years), and infants aged 6-11 months had the second highest incidence (86 cases; 7.3 cases/million person years). During 2009-2014, 865 (74%) of 1173 US-resident case-patients were unvaccinated and 188 (16%) had unknown vaccination status; of 917 vaccine eligible US-resident case-patients, 600 (65%) were reported as having philosophical or religious objections to vaccination. Conclusions: Although the United States has maintained measles elimination since 2000, measles outbreaks continue to occur globally, resulting in imported cases and potential spread. The annual median number of cases and outbreaks more than doubled during 2009-2014 compared with the earlier postelimination years. To maintain elimination, it will be necessary to maintain high 2-dose vaccination coverage, continue case-based surveillance, and monitor the patterns and rates of vaccine exemption. PMID- 26666560 TI - Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer. AB - PURPOSE: To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). MATERIALS AND METHODS: We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. RESULTS: After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. CONCLUSION: Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. PMID- 26666561 TI - How does depth of invasion influence the decision to do a neck dissection in clinically N0 oral cavity cancer? PMID- 26666563 TI - Application of a Regenstrief RELMA V.6.6 to Map Russian Laboratory Terms to LOINC. AB - BACKGROUND: Manual mapping of laboratory data to Logical Observation Identifiers Names and Codes (LOINC) requires a major effort. Application of the LOINC mapping assistant RELMA V.6.6 can reduce the effort required for mapping. The goal of the paper is to perform a semi-automated mapping of Russian laboratory terms to LOINC. METHODS: A semi-automated mapping of the 2563 terms from two clinics in Russia was performed. The first step was automatic mapping using RELMA V.6.6 and LOINC V.2.48 Russian translation by Yaroslavl state medical academy. The second step was a manual expert mapping. To evaluate the correctness of mapping all the mapped terms were reviewed by two experts. RESULTS: The paper presents the results of semi-automatic mapping of Russian laboratory terms to LOINC. Two clinics (A and B) and a laboratory service participated in the project. The following results were achieved: mapping of 86% terms from Clinic A and 87% from Clinic B. It has to be mentioned that 99% of terms used in 2014 were mapped. In total 2398 out of 2563 were mapped. DISCUSSION: The required effort was reasonable and the price of mapping and maintenance was considered as relatively low in comparison to manual methods. CONCLUSION: RELMA V.6.6 and LOINC V.2.48 offer the opportunity of a low effort LOINC mapping even for non-English languages. The study proved that the mapping effort is acceptable and mapping results are on the same level as the manual mapping. PMID- 26666564 TI - A nanocluster beacon based on the template transformation of DNA-templated silver nanoclusters. AB - In this work, we developed a novel light-up nanocluster beacon (NCB) based on shuttling dark silver nanoclusters (NCs) to a bright scaffold through hybridization. The fluorescence enhancement was as high as 70-fold when the two templates were on the opposite sides of the duplexes, enabling sensitive and selective detection of DNA. PMID- 26666562 TI - Cyclosporin promotes neurorestoration and cell replacement therapy in pre clinical models of Parkinson's disease. AB - BACKGROUND: The early clinical trials using fetal ventral mesencephalic (VM) allografts in Parkinson's disease (PD) patients have shown efficacy (albeit not in all cases) and have paved the way for further development of cell replacement therapy strategies in PD. The preclinical work that led to these clinical trials used allografts of fetal VM tissue placed into 6-OHDA lesioned rats, while the patients received similar allografts under cover of immunosuppression in an alpha synuclein disease state. Thus developing models that more faithfully replicate the clinical scenario would be a useful tool for the translation of such cell based therapies to the clinic. RESULTS: Here, we show that while providing functional recovery, transplantation of fetal dopamine neurons into the AAV-alpha synuclein rat model of PD resulted in smaller-sized grafts as compared to similar grafts placed into the 6-OHDA-lesioned striatum. Additionally, we found that cyclosporin treatment was able to promote the survival of the transplanted cells in this allografted state and surprisingly also provided therapeutic benefit in sham-operated animals. We demonstrated that delayed cyclosporin treatment afforded neurorestoration in three complementary models of PD including the Thy1 alpha-synuclein transgenic mouse, a novel AAV-alpha-synuclein mouse model, and the MPTP mouse model. We then explored the mechanisms for this benefit of cyclosporin and found it was mediated by both cell-autonomous mechanisms and non cell autonomous mechanisms. CONCLUSION: This study provides compelling evidence in favor for the use of immunosuppression in all grafted PD patients receiving cell replacement therapy, regardless of the immunological mismatch between donor and host cells, and also suggests that cyclosporine treatment itself may act as a disease-modifying therapy in all PD patients. PMID- 26666567 TI - Orofacial dysfunction, open bite, and myofunctional therapy. AB - SummaryMany orthodontists see open bites as their most demanding assignments; aesthetic issues must be taken into account, the treatment is difficult and the long-term stability unpredictable. Myofunctional treatment may not always be the right choice for this category of malocclusions, but it should be given a serious consideration. We need all the help we can get to treat open bites. PMID- 26666568 TI - Regional facial asymmetries and attractiveness of the face. AB - OBJECTIVE: Facial attractiveness is an important factor in our social interactions. It is still not entirely clear which factors influence the attractiveness of a face and facial asymmetry appears to play a certain role. The aim of the present study was to assess the association between facial attractiveness and regional facial asymmetries evaluated on three-dimensional (3D) images. METHODS: 3D facial images of 59 (23 male, 36 female) young adult patients (age 16-25 years) before orthodontic treatment were evaluated for asymmetry. The same 3D images were presented to 12 lay judges who rated the attractiveness of each subject on a 100mm visual analogue scale. Reliability of the method was assessed with Bland-Altman plots and Cronbach's alpha coefficient. RESULTS: All subjects showed a certain amount of asymmetry in all regions of the face; most asymmetry was found in the chin and cheek areas and less in the lip, nose and forehead areas. No statistically significant differences in regional facial asymmetries were found between male and female subjects (P > 0.05). Regression analyses demonstrated that the judgement of facial attractiveness was not influenced by absolute regional facial asymmetries when gender, facial width to-height ratio and type of malocclusion were controlled (P > 0.05). LIMITATIONS: A potential limitation of the study could be that other biologic and cultural factors influencing the perception of facial attractiveness were not controlled for. CONCLUSIONS: A small amount of asymmetry was present in all subjects assessed in this study, and asymmetry of this magnitude may not influence the assessment of facial attractiveness. PMID- 26666565 TI - Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons. AB - BACKGROUND: In the auditory brainstem, ventral cochlear nucleus (VCN) axons project to the contralateral, but not ipsilateral, medial nucleus of trapezoid body (MNTB), terminating in the calyx of Held. Dorsal VCN neurons, representing high frequencies, synapse with medial MNTB neurons, while low frequency-coding ventral VCN neurons synapse with lateral MNTB neurons, reflecting tonotopic organization. The mechanisms that ensure strictly contralateral targeting and topographic ordering are incompletely understood. Here we examined the roles of ephrin-A signaling in both types of targeting. RESULTS: Ephrin-A2 and ephrin-A5 are expressed in VCN cells during late embryonic and early postnatal development. At these ages ephrin-A2 is expressed in axons surrounding MNTB and ephrin-A5 is expressed in MNTB principal neurons. Ephrin-A2/A5 double knockout mice displayed axon targeting errors in which VCN axons project to MNTB on both sides of the brainstem, where they terminate in calyceal endings. Ephrin-A2 and ephrin-A5 single knockout mice showed a similar phenotype. In contrast to effects on contralateral targeting, ephrin-A2/A5 double knockout mice showed no defects in formation of tonotopically ordered projections from VCN to MNTB. CONCLUSIONS: These findings demonstrate that distinct mechanisms regulate targeting of VCN axons to the contralateral MNTB and targeting to appropriate tonotopic locations. Ephrin-A signaling plays a similar role to ephrin-B signaling in the VCN-MNTB pathway, where both classes normally prevent formation of calyceal projections to ipsilateral MNTB. These classes may rely in part on common signaling pathways. PMID- 26666570 TI - Does p-type ohmic contact exist in WSe2-metal interfaces? AB - Formation of low-resistance metal contacts is the biggest challenge that masks the intrinsic exceptional electronic properties of two dimensional WSe2 devices. We present the first comparative study of the interfacial properties between monolayer/bilayer (ML/BL) WSe2 and Sc, Al, Ag, Au, Pd, and Pt contacts by using ab initio energy band calculations with inclusion of the spin-orbital coupling (SOC) effects and quantum transport simulations. The interlayer coupling tends to reduce both the electron and hole Schottky barrier heights (SBHs) and alters the polarity for the WSe2-Au contact, while the SOC chiefly reduces the hole SBH. In the absence of the SOC, the Pd contact has the smallest hole SBH. Dramatically, the Pt contact surpasses the Pd contact and becomes the p-type ohmic or quasi ohmic contact with inclusion of the SOC. Therefore, p-type ohmic or quasi-ohmic contact exists in WSe2-metal interfaces. Our study provides a theoretical foundation for the selection of favorable metal electrodes in ML/BL WSe2 devices. PMID- 26666569 TI - Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B. AB - Bacterial pathogens stimulate periodontitis, the most common osteolytic disease in humans and the most common cause of tooth loss in adults. Previous studies identified leukocytes and their products as key factors in this process. We demonstrate for the first time that osteoblast lineage cells play a critical role in periodontal disease. Oral infection stimulated nuclear localization of NF kappaB in osteoblasts and osteocytes in the periodontium of wild type but not transgenic mice that expressed a lineage specific dominant negative mutant of IKK (IKK-DN) in osteoblast lineage cells. Wild-type mice were also susceptible to bacteria induced periodontal bone loss but transgenic mice were not. The lack of bone loss in the experimental group was linked to reduced RANKL expression by osteoblast lineage cells that led to diminished osteoclast mediated bone resorption and greater coupled new bone formation. The results demonstrate that osteoblast lineage cells are key contributors to periodontal bone loss through an NF-kappaB mediated mechanism. PMID- 26666571 TI - Growing a healthier heart. PMID- 26666573 TI - Catalytic asymmetric conjugate addition of isocyanoacetate to (Z)-3-substituted-2 (4-pyridyl)-acrylonitrile, a reactive class of Michael acceptor. AB - (Z)-3-Substituted-2-(4-pyridyl)-acrylonitriles, a reactive class of Michael acceptors obtained exclusively as a single (Z) isomer, reacted with un substituted isocyanoacetate esters mediated by phase-transfer catalysis to give, after base promoted cyclisation, functionalized imines in up to 94% ee and as a single diastereoisomer. PMID- 26666574 TI - E-TiO, a Novel Stable Polymorph of Titanium Monoxide. AB - For the Ti/O system, three titanium monoxide (TiO) phases (alpha, beta, and gamma) with defective NaCl-type structures and a high-temperature hexagonal phase (H) have been known for decades. In this work, single crystals of a novel polymorph, E-TiO, were synthesized by using a bismuth flux. X-ray diffraction (XRD) revealed a hexagonal crystal structure (a=4.9936(3) A, c=2.8773(2) A, P6? 2m) that is isotypic with E-TaN. While the Ti atoms are surrounded by trigonal prismatic (sixfold coordination) and trigonal planar (threefold coordination) arrangements of O atoms, the O atoms are found in a pseudo-square-pyramidal arrangement of Ti atoms. First-principles calculations of the formation enthalpy and the electron and phonon density of states and crystal orbital Hamilton population (COHP) analysis revealed that E-TiO is more stable than alpha-TiO, which had previously been regarded as the most stable phase at low temperatures. PMID- 26666572 TI - Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. AB - Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity. PMID- 26666575 TI - Caregiver perception of apathy in persons with mild cognitive impairment or Alzheimer's disease: a longitudinal study. AB - OBJECTIVE: Discrepancy between self- and caregiver apathy ratings was examined longitudinally for persons with mild cognitive impairment or Alzheimer's disease. Particular focus was on the distinction between the positive and negative caregiver bias and its predictive value for a clinical diagnosis of apathy. METHOD: Apathy rating discrepancy was based on the apathy evaluation scale. Dyads were categorized depending on whether the caregiver reported fewer deficits (positive caregiver bias) or more deficits (negative caregiver bias) than the cognitively impaired person did. RESULTS: Caregiver ratings and rating discrepancy showed a significant increase from baseline to follow-up. By contrast, self- and clinician ratings showed no change across the two time points. Ratings with a negative caregiver bias remained stable, while those with a positive caregiver bias showed a significant increase in the caregiver ratings but also a significant decrease in the self-ratings. A negative caregiver bias at baseline was significantly related to greater likelihood of having clinical apathy at follow-up, adjusted for an array of control variables. CONCLUSION: Positive and negative caregiver bias should be distinguished, as they seem to reflect distinct dyadic processes and are relevant for clinical outcome. Furthermore, negative rating discrepancies can be considered a risk factor for developing apathy. PMID- 26666577 TI - Bah humbug: Unexpected Christmas cards and the reciprocity norm. AB - The reciprocity norm refers to the expectation that people will help those who helped them. A well-known study revealed that the norm is strong with Christmas cards, with 20% of people reciprocating a Christmas card received from a stranger. I attempted to conceptually replicate and extend this effect. In Study 1, 755 participants received a Christmas card supposedly from a more- versus less similar stranger. The reciprocation rate was unexpectedly low (2%), which did not allow for a test of a similarity effect. Two potential reasons for this low rate were examined in Study 2 in which 494 participants reported their likelihood of reciprocating a Christmas card from a stranger as well as their felt suspicions/threat about the card and their frequency of e-mail use. Reciprocation likelihood was negatively correlated with perceived threat/suspicion and e-mail use. It appears that reciprocating a gift from a stranger in offline settings may be less likely than expected. PMID- 26666578 TI - A case of myeloid neoplasm with FIP1L1-PDGFRA rearrangement without marked peripheral blood eosinophilia. AB - We report a 29-year-old man with double hip pain and lower limb weakness for 6 months with myeloid neoplasm with FIP1L1-PDGFRA rearrangement without marked peripheral blood eosinophilia. Nested reverse transcription polymerase chain reaction demonstrated that bone marrow was positive for FIP1L1-PDGFRA rearrangement. The patient consequently received imatinib treatment at a dosage of 100 mg daily. Two weeks later, white blood cell counts were normalized. The double hip pain disappeared gradually. FIP1L1-PDGFRA fusion by reverse transcription polymerase chain reaction was still positive at 3 months. His 9 month post-treatment complete blood cell count, peripheral blood and bone marrow biopsy were all normal. FIP1L1 was unrearranged. The patient continues to be treated with imatinib 100 mg daily for more than 2 years with no recurrence. The presence of PDGFRA rearrangement in this case conferred a high sensitivity to imatinib treatment and a favorable clinical outcome. PMID- 26666576 TI - The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer. AB - Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs, and has been associated with poor clinical outcome. The aim of this study is to investigate the significance of tumor G-CSF expression in the chemosensitivity of uterine cervical cancer. The clinical data of recurrent or advanced cervical cancer patients who were treated with platinum based chemotherapy were analyzed. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for the development of chemoresistance in G-CSF-producing cervical cancer, focusing on myeloid-derived suppressor cells (MDSC). As a result, the tumor G-CSF expression was significantly associated with increased MDSC frequencies and compromised survival. In vitro and in vivo experiments demonstrated that the increased MDSC induced by tumor-derived G-CSF is involved in the development of chemoresistance. The depletion of MDSC via splenectomy or the administration of anti-Gr-1 antibody sensitized G-CSF-producing cervical cancer to cisplatin. In conclusion, tumor G-CSF expression is an indicator of an extremely poor prognosis in cervical cancer patients that are treated with chemotherapy. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy as a treatment for G-CSF-producing cervical cancer. PMID- 26666579 TI - Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-AARP diet and health cohort. AB - Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH-AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow-up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self-reported diabetes and energy-adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR = 1.20, 95% CI 1.02-1.42, p-trend = 0.03), red meat (HR = 1.22, 95% CI 1.01-1.48, p-trend = 0.02), high-temperature cooked meat (HR = 1.21, 95% CI 1.00-1.45, p-trend = 0.02), grilled/barbequed meat (HR = 1.24, 95% CI 1.03-1.50, p-trend = 0.007), well/very well done meat (HR = 1.32, 95% CI 1.10-1.58, p-trend = 0.005) and heme iron from red meat (Q4 vs. Q1: HR = 1.21, 95% CI 1.01-1.45, p-trend = 0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02-1.74, p-trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk. PMID- 26666580 TI - Extracorporeal photopheresis versus standard treatment for acute graft-versus host disease after haematopoietic stem cell transplantation in paediatric patients. AB - BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT) occurring in 8% to 59% of the recipients. Currently, the therapeutic mainstay for aGvHD is corticosteroids. However, there is no established standard treatment for steroid refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and re-infusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014. OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL) (Issue 9, 2015), MEDLINE (PubMed) and EMBASE (Ovid) databases from their inception to 23 September 2015. We searched the reference lists of potentially relevant studies without any language restrictions. We searched eight trial registers and four conference proceedings on 29 September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in paediatric patients with aGvHD after HSCT. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author. MAIN RESULTS: We identified no additional studies in the 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the treatment of aGvHD in paediatric patients after HSCT is unknown and its use should be restricted within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2015 review update brought about no additions to these conclusions. PMID- 26666581 TI - Extracorporeal photopheresis versus alternative treatment for chronic graft versus-host disease after haematopoietic stem cell transplantation in paediatric patients. AB - BACKGROUND: Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic GvHD are corticosteroids that are frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory chronic GvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8 methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014. OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of chronic GvHD in children and adolescents after haematopoietic stem cell transplantation. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL) (Issue 9, 2015), MEDLINE and EMBASE databases from their inception to 23 September 2015. We searched the reference lists of potentially relevant studies without any language restriction. We searched eight trial registers and five conference proceedings on 29 September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in paediatric patients with chronic GvHD after haematopoietic stem cell transplantation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author. MAIN RESULTS: No additional studies were identified in this 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs cannot be evaluated since the original version of this review and the first review update found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, patients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP. PMID- 26666583 TI - Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom. AB - AIMS: The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes-associated complications can explain the apparent relationship between diabetic foot ulcers and death. METHODS: We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death. RESULTS: Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated. CONCLUSIONS: Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up. PMID- 26666582 TI - Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors. AB - Thermodynamic integration (TI) can provide accurate binding free energy insights in a lead optimization program, but its high computational expense has limited its usage. In the effort of developing an efficient and accurate TI protocol for FabI inhibitors lead optimization program, we carefully compared TI with different Amber molecular dynamics (MD) engines (sander and pmemd), MD simulation lengths, the number of intermediate states and transformation steps, and the Lennard-Jones and Coulomb Softcore potentials parameters in the one-step TI, using eleven benzimidazole inhibitors in complex with Francisella tularensis enoyl acyl reductase (FtFabI). To our knowledge, this is the first study to extensively test the new AMBER MD engine, pmemd, on TI and compare the parameters of the Softcore potentials in the one-step TI in a protein-ligand binding system. The best performing model, the one-step pmemd TI, using 6 intermediate states and 1 ns MD simulations, provides better agreement with experimental results (RMSD = 0.52 kcal/mol) than the best performing implicit solvent method, QM/MM-GBSA from our previous study (RMSD = 3.00 kcal/mol), while maintaining similar efficiency. Briefly, we show the optimized TI protocol to be highly accurate and affordable for the FtFabI system. This approach can be implemented in a larger scale benzimidazole scaffold lead optimization against FtFabI. Lastly, the TI results here also provide structure-activity relationship insights, and suggest the parahalogen in benzimidazole compounds might form a weak halogen bond with FabI, which is a well-known halogen bond favoring enzyme. PMID- 26666584 TI - Sequential Closure of Loop Structures Forms the Folding Nucleus during the Refolding Transition of the Escherichia coli Adenylate Kinase Molecule. AB - The ensemble of conformers of globular protein molecules immediately following transfer from unfolding to folding conditions is assumed to be collapsed though still disordered, as the first steps of the folding pathway are initiated. In order to test the hypothesis that long loop closure transitions are part of the initiation of the folding pathway, our groups are studying the initiation of the folding transition of a model protein by time-resolved excitation energy transfer (trFRET) detected fast kinetics experiments. Site-specific double labeling is used to study the timing of conformational transitions of individual loop forming chain segments at the microsecond time regime. Previously, it was shown that at least three long loops in the Escherichia coli adenylate kinase (AK) molecule close within the first 5 ms of folding of AK, while the main global folding transition occurs in a time regime of seconds. In order to enhance the time resolution of the kinetics experiments to the microsecond time regime and determine the rate of closure of the two N terminal loops (loop I residues 1-26 and loop II residues 29-72), we applied a continuous flow based double kinetics experiment. These measurements enabled us to obtain a microsecond series of transient time dependent distributions of distances between the ends of the labeled loops. Analysis of the trFRET experiments show that the N terminal loop (loop I) is closed within less than 60 MUs after the initiation of refolding. Loop II is also mostly closed within that time step but shows an additional small reduction of the mean end-to-end distance in a second phase at a rate of 0.005 MUs(-1). This second phase can either reflect tightening of a loosely closed loop in the ensemble of conformers or may reflect two subpopulations in the ensemble, which differ in the rate of closure of loop II, but not in the rate of closure of loop I. This study shows the very fast closure of long loops in the otherwise disordered backbone and fine details of the very early hidden pretransition state steps that are essential for the fast and efficient folding of the protein molecule. PMID- 26666585 TI - High-throughput investigation of endothelial-to-mesenchymal transformation (EndMT) with combinatorial cellular microarrays. AB - In the developing heart, a specific subset of endocardium undergoes an endothelial-to-mesenchymal transformation (EndMT) thus forming nascent valve leaflets. Extracellular matrix (ECM) proteins and growth factors (GFs) play important roles in regulating EndMT but the combinatorial effect of GFs with ECM proteins is less well understood. Here we use microscale engineering techniques to create single, binary, and tertiary component microenvironments to investigate the combinatorial effects of ECM proteins and GFs on the attachment and transformation of adult ovine mitral valve endothelial cells to a mesenchymal phenotype. With the combinatorial microenvironment microarrays, we utilized 60 different combinations of ECM proteins (Fibronectin, Collagen I, II, IV, Laminin) and GFs (TGF-beta1, bFGF, VEGF) and were able to identify new microenvironmental conditions capable of modulating EndMT in MVECs. Experimental results indicated that TGF-beta1 significantly upregulated the EndMT while either bFGF or VEGF downregulated EndMT process markedly. Also, ECM proteins could influence both the attachment of MVECs and the response of MVECs to GFs. In terms of attachment, fibronectin is significantly better for the adhesion of MVECs among the five tested proteins. Overall collagen IV and fibronectin appeared to play important roles in promoting EndMT process. Great consistency between macroscale and microarrayed experiments and present studies demonstrates that high-throughput cellular microarrays are a promising approach to study the regulation of EndMT in valvular endothelium. Biotechnol. Bioeng. 2016;113: 1403-1412. (c) 2015 Wiley Periodicals, Inc. PMID- 26666586 TI - Physical activity in adulthood: genes and mortality. AB - Observational studies report a strong inverse relationship between leisure-time physical activity and all-cause mortality. Despite suggestive evidence from population-based associations, scientists have not been able to show a beneficial effect of physical activity on the risk of death in controlled intervention studies among individuals who have been healthy at baseline. On the other hand, high cardiorespiratory fitness is known to be a strong predictor of reduced mortality, even more robust than physical activity level itself. Here, in both animals and/or human twins, we show that the same genetic factors influence physical activity levels, cardiorespiratory fitness, and risk of death. Previous observational follow-up studies in humans suggest that increasing fitness through physical activity levels could prolong life; however, our controlled interventional study with laboratory rats bred for low and high intrinsic fitness contrast with these findings. Also, we find no evidence for the suggested association using pairwise analysis among monozygotic twin pairs who are discordant in their physical activity levels. Based on both our animal and human findings, we propose that genetic pleiotropy might partly explain the frequently observed associations between high baseline physical activity and later reduced mortality in humans. PMID- 26666588 TI - Mean platelet volume in young children with urinary tract infection. AB - Mean platelet volume (MPV) has not yet been well-established in urinary tract infection (UTI). The purpose of this study was to evaluate the role of MPV as an acute phase reactant in children with UTI. Data from 118 young children (<2 years) with UTI between 2012 and 2013 were grouped as acute pyelonephritis (APN) and lower UTI according to the dimercaptosuccinic acid (DMSA) scan abnormalities. MPV, platelet distribution width (PDW) platelet count, and other infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were measured. WBC (P = 0.001), ESR (P = 0.005), CRP (P < 0.001) and MPV levels (P = 0.011) were significantly higher in the APN group than those in the lower UTI group. MPV positively correlated with PDW, CRP and negatively with platelet count. Multiple logistic regression analyses showed that CRP and MPV were independent predictive factors for APN patients. However, the area under the Receiver Operating Characteristic (ROC) curve analysis for MPV was lower than CRP. Our results suggest that MPV can be an inflammatory marker in UTI, but the predictive value of MPV was not superior to CRP in the diagnosis of APN. PMID- 26666589 TI - The role of anti-VEGF agents in myopic choroidal neovascularization: Current standards and future outlook. AB - INTRODUCTION: The global prevalence of pathologic myopia is 0.9-3.1%, and visual impairment is found in 0.1-0.5% of European and 0.2-1.4% of Asian studies. Myopic choroidal neovascularization (mCNV) affects 5.2-11.3% of pathologic myopia patients and is a leading cause of vision impairment in the working-age population. Characteristic morphological changes and visual-acuity decrease are diagnostic features. Vascular-Endothelial-Growth-Factor (VEGF) has been identified as a trigger for pathologic neovascularization in these highly myopic patients. AREAS COVERED: We cover the epidemiology, pathology and diagnostic aspects of mCNV. The history of therapeutic interventions is described, followed by an overview of current standard-of-care (SOC)-blocking VEGF using bevacizumab (off-label), ranibizumab or aflibercept and improving vision up to 13.5-14.4 letters. Despite good efficacy, an unmet medical need remains. We summarize ongoing and future developments of new drugs to treat or potentially cure mCNV. EXPERT OPINION: mCNV is a major global health concern. Early detection and treatment is key for a satisfying outcome. The current SOC, VEGF inhibitors, affords good therapeutic efficacy and reasonable disease stabilization with few intravitreal treatments per year. However, the long-term prognosis is still unsatisfactory, and side-effects like chorioretinal atrophy development are of concern. Therefore, efforts should be intensified to develop more effective therapies. PMID- 26666590 TI - Maternal and infant characteristics influencing the anogenital distance and penile length in newborns. AB - Recent studies have suggested that maternal characteristics can affect reproductive health of offspring, possibly through pre-natal hormonal influence. Anogenital distance (AGD) is an anthropometric measure which is a sensitive reproductive endpoint of masculinisation. It provides a read-out of pre-natal androgen exposure and has been associated with several reproductive health outcomes in humans. We studied AGD and stretched penile length (SPL) in a large, racially homogenous sample of consecutive newborns to understand their association with maternal and infant characteristics. A prospective cross sectional study involving measurement of AGD and SPL at birth was performed by a single trained observer. A total of 1077 newborns (553 males and 524 females) were included in final anthropometric analysis. The mean AGD of males was 2.56 +/ 0.31 cm, and the mean AGD of females was 1.54 +/- 0.17 cm. The mean SPL of males was 3.31 +/- 0.38 cm. On multiple regression analysis, for both males and females, birthweight (beta = 0.229, P < 0.001 and beta = 0.135, P < 0.001, respectively) was modest but significant predictor for AGD. For SPL, only gestational age (beta = 0.054, P < 0.001) was found to be statistically significant predictor. There was no significant association observed for gravidity, parity and maternal age with both AGD and SPL. Thus, no maternal characteristics (age, gravidity, parity) influence AGD or SPL in human infants. PMID- 26666587 TI - Prevalence of 7 sexually transmitted organisms by multiplex real-time PCR in Fallopian tube specimens collected from Saudi women with and without ectopic pregnancy. AB - BACKGROUND: Ectopic pregnancy (EP) is associated with maternal morbidity and occasionally mortality during the first trimester. A history of sexually transmitted infection (STI) and pelvic inflammatory disease have been implicated as major risk factors for EP. Our aim was to measure the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae, Mycoplasma genitalium (MG), Ureaplasma parvum/urealyticum, Gardnerella vaginalis, Trichomonas vaginalis and herpes simplex virus (HSV)-1&2 in Fallopian tubes collected from EP and the results were compared with those obtained from total abdominal hysterectomy (TAH) and tubal ligation. METHODS: This was a prospective case-control study and tubal samples were collected from 135 Saudi women recruited from 3 centres in the Western region as follow: 84 EPs, 20 TAH and 31 tubal ligations. Multiplex TaqMan PCR was performed using an IVD CE kit for the simultaneous detection of candidate pathogens following DNA extraction. RESULTS: Infections were detected in 31.8 % of the 135 participants either as single (11.1 %) or co-infections (20.7 %) and the frequencies were significantly higher in EP (42.85 %) compared with control (13.72 %). The rates of CT (27.4 %; P = 0.001); MG (20.2 %; P = 0.009) and HSV 1/2 (21.4 %; P = 0.01) were significantly higher in EP. No significant difference between the study groups was observed for the other pathogens (P > 0.05). Binary logistic regression also showed that infection with >= 2 pathogens (OR 4.9; 95 % CI: 2.2 - 11.6; P = 0.006), CT (OR 3.07; 95 % CI: 1.3 - 12.3; P = 0.002), MG (OR 2.3; 95 % CI: 1.1 - 8.6; P = 0.03) and HSV-1/2 (OR 1.7; 95 % CI: 0.75 - 5.7; P = 0.004) were associated with a significantly higher risk of developing EP. CONCLUSIONS: STIs are frequent in the upper genital tract of Saudi women during the reproductive age and, CT, MG and HSV-1/2 were more prevalent in EP. The observed high rates of co-infection advocate the necessity of establishing national guidelines and/or screening program utilising multiplex PCR approach for the detection of common STIs among high risk groups in the kingdom. Further studies are needed to measure the adverse reproductive outcomes associated with STIs in Saudi Arabia. PMID- 26666591 TI - Foxc1 Expression in Early Osteogenic Differentiation Is Regulated by BMP4-SMAD Activity. AB - FOXC1 is an important regulator of the initial steps in intramembranous and endochondral ossification processes. As BMP signalling is a key initiator of these processes, we sought to determine whether Foxc1 expression is regulated by such signalling factors. BMP4 treatment of C2C12 cells resulted in an induction in Foxc1 mRNA levels. Chromatin immunoprecipitation assays demonstrated that SMAD proteins interacted with the mouse Foxc1 promoter approximately 300 bp upstream of the transcription start site. This ChIP positive region was cloned into a luciferase reporter and demonstrated to be responsive to BMP4 stimulation. Reduction of Foxc1 levels in C2C12 cells though siRNA impaired BMP4 osteogenic differentiation. In contrast, BMP4 treatment repressed Foxc1 expression in 10T1/2 or D1-ORL mesenchymal cells and MC3T3 preosteoblasts. Finally, siRNA knock-down of Foxc1 in MC3T3 cells resulted in an induction of markers of osteoblast differentiation and an accelerated mineralization. These data indicate that Foxc1 expression is regulated by BMP4 and FOXC1 functions in the commitment of progenitor cells to the osteoblast fate and its expression is reduced when differentiation proceeds. J. Cell. Biochem. 117: 1707-1717, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26666592 TI - Novel CE-MS technique for detection of high explosives using perfluorooctanoic acid as a MEKC and mass spectrometric complexation reagent. AB - To address the need for the forensic analysis of high explosives, a novel capillary electrophoresis mass spectrometry (CE-MS) technique has been developed for high resolution, sensitivity, and mass accuracy detection of these compounds. The technique uses perfluorooctanoic acid (PFOA) as both a micellar electrokinetic chromatography (MEKC) reagent for separation of neutral explosives and as the complexation reagent for mass spectrometric detection of PFOA explosive complexes in the negative ion mode. High explosives that formed complexes with PFOA included RDX, HMX, tetryl, and PETN. Some nitroaromatics were detected as molecular ions. Detection limits in the high parts per billion range and linear calibration responses over two orders of magnitude were obtained. For proof of concept, the technique was applied to the quantitative analysis of high explosives in sand samples. PMID- 26666593 TI - Prenatal Discussion of Contraceptive Options in Teenage Pregnancies. AB - OBJECTIVE: To determine if contraceptive options are discussed during prenatal care among pregnant teenagers. MATERIALS AND METHOD: Hospital and outpatient clinical records were reviewed for teenagers between the ages 12 and 19, inclusive, who delivered at the University of Texas Medical Branch in Galveston (UTMB) John Sealy Hospital and received prenatal care at one of the UTMB affiliated ambulatory clinics. RESULTS: A total of 244 postpartum teenagers were included in this study. The mean age was 17.6 +/- 1.2 years. The majority of teenagers were Hispanic (57%), followed by white (34%) and black (9%). Of the patients, 41% had less than 10 prenatal visits. Only 14% of the patients had a discussion about contraception during these prenatal visits, most of which occurred after 29 weeks of gestation. CONCLUSIONS: Pregnant teenagers are not frequently counseled about postpartum contraceptives. When counseling does occur, it happens in the third trimester, which may not provide enough time for a teenager to thoroughly consider contraceptive options. Guidelines on when providers should discuss postpartum contraception are necessary. PMID- 26666594 TI - The Symptoms of Gastroesophageal Reflux Disease Correlate with High Body Mass Index, the Aspartate Aminotransferase/Alanine Aminotransferase Ratio and Insulin Resistance in Japanese Patients with Non-alcoholic Fatty Liver Disease. AB - OBJECTIVE: This study was designed to compare the association between the body mass index (BMI) and symptoms of gastroesophageal reflux disease (GERD) in allegedly normal subjects undergoing regular medical checkups and subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). Additionally, the correlation between the BMI and GERD symptoms was evaluated in subjects with NAFLD. METHODS: This study included 50 patients with NAFLD and 228 normal subjects evaluated during regular medical checkups. The height, weight, BMI, frequency scale for the symptoms of GERD (FSSG), and serum concentrations of triglycerides and gamma-GTP were compared between the two groups. In the NAFLD group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations were measured and insulin resistance was calculated using the quantitative insulin sensitivity check index (QUICKI). RESULTS: The total FSSG score moderately correlated with the BMI in the NAFLD group (r=0.342, p=0.015), but correlated negatively in the control group (r=-0.014, p=0.831). The FSSG score in the NAFLD group also negatively correlated with the AST/ALT ratio (r= 0.319) and insulin resistance calculated using the QUICKI score (r=-0.288). The BMI in the NAFLD group moderately correlated with the acid-reflux related score on the FSSG (r=0.389), and both the AST/ALT ratio (r=-0.344) and QUICKI score (r= 0.330) negatively correlated with the dyspepsia score on the FSSG. CONCLUSION: Obesity evaluated by the BMI was a significant risk factor for the exacerbation of GERD symptoms in subjects with NAFLD. PMID- 26666595 TI - Prevalence and Predictive Factors of Irritable Bowel Syndrome in a Community dwelling Population in Japan. AB - OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by chronic, relapsing abdominal pain or discomfort and is associated with disturbed defecation. The pathogenesis of IBS is multifactorial. The aim of this study was to investigate the prevalence of IBS using the Rome III criteria and to assess the effects of mental and lifestyle factors on IBS in a community-dwelling population in Japan. METHODS: The diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. The questionnaire was administered to 993 volunteers who participated in the Iwaki Health Promotion Project 2013. Diet was assessed with a validated brief-type self administered diet history questionnaire. Dietary patterns based on 52 predefined food groups [energy-adjusted food (g/d)] were extracted using a principal component analysis. The Center for Epidemiologic Studies Depression Scale with a cut-off point of 16 was used to assess the prevalence of depression. RESULTS: A total of 61 subjects (6.1%) were classified as having IBS. Three dietary patterns were identified: "Healthy", "Western" and "Alcohol and accompanying" dietary patterns. After adjusting for potential confounders, the "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS. CONCLUSION: We found that an "Alcohol and accompanying" dietary pattern and depression were related to the risk of IBS in a Japanese community population. However, we could not rule out the possibility of some selection bias. Further studies with longitudinal observations are therefore warranted. PMID- 26666596 TI - Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial. AB - OBJECTIVE: Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. METHODS: The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by >=5% before starting treatment with PEG-IFN plus RBV. RESULTS: Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of >=5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a >=5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. CONCLUSION: Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate. PMID- 26666597 TI - Body Mass Index Is Associated with Hypertension in Japanese Young Elderly Individuals: Findings of the New Integrated Suburban Seniority Investigation. AB - OBJECTIVE: This study aimed to investigate the association between BMI at 65 years of age and the development of hypertension during the subsequent five years. METHODS: A total of 1,003 participants (65 years of age) who had no history of myocardial infarction and/or hypertension at baseline health check-ups (1996-2005) and participated in a secondary health check-up when the subjects reached 70 years of age were analyzed. RESULTS: Using fully adjusted models, men with a BMI of <18.5 [odds ratio (OR), 4.08; 95% confidence interval (CI), 1.32 1.83], BMI of 23.0-24.9 (OR, 2.00; 95% CI, 1.18-3.40) and BMI of >=25.0 (OR, 1.98; 95% CI, 1.10-3.56) were found to be at higher risk of developing hypertension than did those with a BMI of 18.5-22.9. CONCLUSION: Leanness or being overweight/obese at age 65 increases the risk of subsequent hypertension. PMID- 26666598 TI - Effect of Pregnancy and Delivery on the Renal Function and the Prognosis of Patients with Chronic Kidney Disease Stage 3 Caused by Immunoglobulin A Nephropathy. AB - OBJECTIVE: Immunoglobulin A nephropathy (IgAN) exhibits a peak onset that coincides with the reproductive age. Therefore, many young women with IgAN may become pregnant. However, the outcome of pregnancy in women with renal diseases remains controversial, and the characteristics and outcome of pregnancy in IgAN patients must be further evaluated. METHODS: A prospective follow-up study of 64 pregnant women with IgAN was performed by analyzing the laboratory data and prognosis. To clarify the influence of renal insufficiency, we compared these patients according to the chronic kidney disease (CKD) stage with special attention to CKD stage 3 [N=16 in total, N=9 for estimated glomerular filtration rate (eGFR) >=45 mL/min, N=7 for <45 mL/min]. RESULTS: We found that pregnancy and delivery did not produce any significant changes in the renal function for patients with CKD stage 3 (>=45 mL/min) at five years after delivery, although proteinuria was elevated at 30 weeks of pregnancy and at three months after delivery. However, only for patients with CKD stage 3 (<45 mL/min) was there a significant deterioration in the eGFR at five years after delivery. Additionally, the data of pregnant women with CKD stage 3 were compared with those of 22 nonpregnant women with similar clinical and demographic characteristics. CONCLUSION: Pregnant patients with IgAN (CKD stage 3, eGFR >=45 mL/min) did not exhibit any significant reduction in the renal function at five years after delivery as compared with the baseline, which was similar to the findings in nonpregnant patients. Thus, while pregnancy with CKD stage 3 (eGFR >=45 mL/min) was not a risk factor, patients with CKD stage 3 (eGFR <45 mL/min) showed a worsened renal function five years after delivery. PMID- 26666599 TI - Eicosapentaenoic Acid (EPA) Decreases the All-Cause Mortality in Hemodialysis Patients. AB - OBJECTIVE: Atherosclerosis, which causes cardiovascular disease, is a major cause of death in hemodialysis (HD) patients. Eicosapentaenoic acid (EPA), an anti hyperlipidemic agent, is known to have antioxidative or anti-inflammatory effects, resulting in improvements in atherosclerosis. In the present study, we examined whether EPA improves the all-cause mortality in patients receiving regular HD therapy. METHODS: We enrolled 176 patients treated with maintenance HD therapy and performed a longitudinal observational cohort study for three years. We divided the patients into two groups based on whether or not the received EPA treatment [EPA(+) and EPA(-), respectively]. The primary end-point was all-cause death. We also matched the two groups using propensity score matching and examined the effect of EPA. RESULTS: Before matching, the all-cause mortality rates were 24.0% in the EPA(+) and 11.8% in the EPA(-) groups, which were significantly different (p=0.044). After propensity score matching, the EPA(+) group still showed a significantly better prognosis than the EPA(-) group (p=0.038). A multivariate analysis showed that EPA treatment significantly reduced the risk of all-cause mortality both before and after propensity score matching. CONCLUSION: EPA treatment is independently associated with lower mortality in HD patients. PMID- 26666600 TI - Correlation between the Occlusion Site and Clinical Outcome after Acute Ischemic Stroke. AB - OBJECTIVE: The significance of early mild clinical improvement after intravenous tissue plasminogen activator (IVtPA) treatment is unclear. Therefore, we examined whether the timing of clinical improvement after IVtPA predicted the clinical outcome at 3 months. METHODS: Consecutive patients with acute cerebral infarction in the anterior circulation who received IVtPA treatment within 3 hours of the onset of symptoms were enrolled in the study. Patients were classified according to the timing of clinical improvement [early responder (ER), National Institutes of Health Stroke Scale (NIHSS) score improved >=4 points or who had a score of 0 within 2 hours after IVtPA; late responder (LR), a similar improvement between 2 and 24 hours; and non-responder (NR)] and according to the arterial occlusion site (P group, internal carotid artery and proximal middle cerebral artery M1 region; and D group, distal M1 and M2). RESULTS: Ninety-three patients [median age, 74 (67-79) years; 54 men (58%); median NIHSS score, 11 (7-16)] were enrolled in the study. The P group consisted of 48 (52%) patients and the D group consisted of 45 (48%) patients. Thirty-eight patients (41%) were classified as ERs, 20 (22%) as LRs, and 35 (38%) as NRs. On a multivariate regression analysis, the P group [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.08-10.45; p=0.036] and NR (OR, 4.04; 95% CI, 1.29-14.27; p=0.016) were independent predictors of a poor outcome. ER (47%, p=0.01) and LR (45%, p=0.01) patients showed fewer poor outcomes than NR (77%) patients, but the rate did not differ significantly between the ER and LR patients. CONCLUSION: Early mild clinical recovery did not predict a good outcome. The occlusion site was a stronger predictor of clinical improvement after IVtPA administration. PMID- 26666601 TI - Two Cases of Intravascular Lymphoma Diagnosed by Gastrointestinal Endoscopic Biopsy. AB - Two cases of intravascular lymphoma (IVL) were diagnosed by endoscopic biopsy. Both patients were admitted to our hospital with a fever of an unknown origin. An elevated serum level of soluble interleukin-2 receptor antibody suggested IVL. An upper gastrointestinal endoscopy was performed. A biopsy of both the reddened and normal gastroduodenal mucosa (Case 1) and a biopsy of a gastric antral ulcer, multiple polyploid lesions resembling submucosal tumors in the duodenum, and the patient's normal mucosa (Case 2) revealed vascular infiltration by CD20-positive atypical lymphocytes, confirming the diagnosis of IVL. The performance of a gastrointestinal biopsy for suspected IVL is important, even if there are no visible endoscopic abnormalities. PMID- 26666602 TI - A Duodenal Ulcer Caused by Pancreatic Ductal Hypertension with Chronic Pancreatitis. AB - We herein describe the case of a 67-year-old woman with a duodenal ulcer thought to be caused by elevated pancreatic ductal pressure. The patient complained of continuous upper abdominal pain. Her medical history included idiopathic chronic pancreatitis. Endoscopy revealed a huge duodenal ulcer located on the inferior duodenal angle, which had not been seen on endoscopic retrograde pancreatography two months previously. A combination study using endoscopy and contrast imaging confirmed the relationship between the duodenal ulcer and the pancreatic branch duct. To our knowledge, this is the first case of duodenal ulcer thought to be caused by elevated pancreatic ductal pressure. PMID- 26666603 TI - Atrial Fibrillation Arising from the Left Atrial Appendage. AB - A 63-year-old patient presented for curative treatment of drug-resistant paroxysmal atrial fibrillation (AF). After pulmonary vein antrum isolation was achieved, AF could be still induced and persisted, while rapid activation at the left atrial appendage was conducted to the left atrium in a decremental conduction manner. A step-wise incremental discrete radiofrequency energy application at the ostium of left atrial appendage completely eliminated the AF. Neither AF nor atrial tachyarrhythmias reappeared, even under isoproterenol infusion and vigorous rapid atrial stimulations. The patient has experienced no symptoms or exhibited ECG evidence of AF during a 6-month follow-up. PMID- 26666604 TI - Cardiac Papillary Fibroelastoma Originating from the Mitral Valve Chordae. AB - Cardiac papillary fibroelastoma (CPF) is a rare benign primary cardiac neoplasm. In particular, CPF originating from the mitral valve chordae is extremely rare. A 74-year-old man was hospitalized for the evaluation of a cardiac mass in the left ventricle. Echocardiography revealed a mobile, spherical, pedunculated 2.1*2.1 cm mass at the mitral valve chordae with no mitral regurgitation. The patient underwent excision of the mass without repairing the mitral valve. A histological examination confirmed the mass to be a papillary fibroelastoma. PMID- 26666605 TI - Non-Islet Cell Tumor Hypoglycemia Is Caused by Big IGF-II in a Patient with a Carcinosarcoma of the Uterus. AB - We report a 72-year-old Japanese woman with severe hypoglycemia. The laboratory data, which revealed the suppression of serum insulin, suggested the existence of non-islet cell tumor hypoglycemia (NICTH). Abdominal computed tomography demonstrated the presence of a huge uterine tumor. The patient was treated with a continuous infusion of glucose, but died of sepsis on day 46. An autopsy revealed the pathological diagnosis to be a carcinosarcoma of the uterus. Interestingly, an immunohistochemical study discovered the expression of insulin-like growth factor (IGF)-II in both the carcinoma and sarcoma cells. In addition, an immunoblot analysis of blood samples revealed the presence of circulating big IGF II. Therefore, this is a novel case of NICTH that was caused by a uterine carcinosarcoma. PMID- 26666606 TI - Hydroxyurea-induced Pneumonitis in a Patient with Chronic Myelomonocytic Leukemia: An Autopsy Case. AB - We describe the case of an 85-year-old man diagnosed with chronic myelomonocytic leukemia whose disease was treated with hydroxyurea for 3 months. He developed respiratory symptoms that were extensively investigated. Despite the intensive treatment, he died of respiratory failure eleven days later. An autopsy revealed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. A drug lymphocyte stimulation test was positive for hydroxyurea. Taken together these findings demonstrated that severe interstitial pneumonitis was induced by this drug. Physicians using hydroxyurea must be aware of its potentially life-threatening pulmonary toxicity. PMID- 26666607 TI - Autoimmune Pulmonary Alveolar Proteinosis Following Pulmonary Aspergillosis. AB - A 59-year-old man, ex-smoker, was diagnosed with pulmonary aspergillosis according to chest radiography findings of a fungus ball and Aspergillus fumigatus detection in the bronchial lavage fluid. Two years after anti-fungal therapy, he was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP) according to a crazy paving pattern in computed tomography scans of the chest, milky bronchoalveolar lavage effluent, and positive anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody in the serum. The patient ultimately died of respiratory failure caused by APAP four months after GM-CSF therapy commenced. Aspergillus infection may thus be associated with the onset and progression of APAP and tolerance to GM-CSF therapy. PMID- 26666608 TI - Ehlers-Danlos Syndrome Type IV with Bilateral Pneumothorax. AB - A 17-year-old teen was hospitalized with bilateral pneumothorax. After the bilateral lungs were expanded using catheter tubes, he fully recovered and he was discharged from our hospital. He had a history of colon perforation. Ehlers Danlos syndrome (EDS) was suspected due to the combination of colon perforation and pneumothorax, and EDS type IV was confirmed after a genetic study identified a c.1511g>a mutation in the COL3A1 gene. This is the first report of bilateral pneumothorax caused by EDS type IV. Clinicians should consider EDS type IV in the differential diagnosis for bilateral pneumothorax in conjunction with distinct previous histories and radiological findings. PMID- 26666609 TI - Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma. AB - A 44-year-old woman who was diagnosed with anaplastic lymphoma kinase-positive lung adenocarcinoma developed brain metastases, multiple spinal metastases and meningeal dissemination. Crizotinib was administered after the failure of first line chemotherapy. Esophagitis and liver damage were induced by the twice-daily administration of crizotinib at 250 mg and 200 mg, respectively. The alternate day administration of crizotinib (250 mg, twice daily) was able to control disease progression without any adverse effects for several months. We evaluated the relationship between the serum concentration of crizotinib and the development of esophagitis and liver damage. The alternate-day administration of crizotinib is one of the strategies for managing the severe toxicity of crizotinib. PMID- 26666610 TI - Thoracic Empyema Caused by Percutaneous Transhepatic Gallbladder Drainage. AB - Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative to emergency laparoscopic cholecystectomy in high-risk patients with acute cholecystitis. Severe complications of this procedure are rare, except for drainage tube-related complications. A case of thoracic empyema, which is a rare complication of PTGBD, is reported; penetration of the pleural cavity seemed to be the cause of the thoracic empyema. PMID- 26666611 TI - Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu Vaccination in the Elderly. AB - Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season. PMID- 26666612 TI - Successful Allogeneic Stem Cell Transplantation for Severe Aplastic Anemia after Treatment of Lymphoproliferative Disorder Caused by Rabbit Antithymocyte Globulin. AB - Immunosuppressive therapy (IST) with a combination of antithymocyte globulin (ATG) and cyclosporine (CsA) is an effective therapeutic modality for patients with aplastic anemia (AA) who are not eligible for allogeneic stem cell transplantation (Allo-SCT) from a human leukocyte antigen-identical sibling donor. However, there have been reports of some patients developing lymphoproliferative disorder (LPD) after IST for AA. We herein report a case of a 26-year-old man with severe AA (SAA) complicated by LPD after a single course of IST, who was successfully treated with Allo-SCT from an unrelated donor. Two months after starting IST for SAA, he developed LPD in the stomach. CsA was reduced, however, his neutrophil counts decreased, and CsA could not be discontinued. The patient was treated with rituximab monotherapy, and LPD resulted in complete remission. However, he failed IST for SAA and underwent Allo SCT with reduced-intensity conditioning to recover his hematopoiesis. The patient has achieved complete hematopoietic recovery without the recurrence of LPD for five years after transplantation. This is the first report of successful Allo-SCT for SAA after the treatment of LPD caused by the use of rabbit ATG. This case provides useful information for the management of SAA with the development of LPD after IST. PMID- 26666613 TI - Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma. AB - Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late onset anticonvulsant hypersensitivity syndrome. PMID- 26666614 TI - Rituximab-containing Chemotherapy (R-CHOP)-induced Kaposi's Sarcoma in an HIV negative Patient with Diffuse Large B Cell Lymphoma. AB - Rituximab treatment may cause or exacerbate Kaposi's sarcoma (KS) in patients with human immunodeficiency virus (HIV)-associated multicentric Castleman's disease. Despite the widespread use of rituximab, rituximab-induced KS has not yet been reported in HIV-negative patients with diffuse large B cell lymphoma (DLBCL). We herein report a case of KS that developed after undergoing rituximab containing chemotherapy in an HIV-negative patient with DLBCL. An 84-year-old man who received rituximab-containing chemotherapy for the treatment of DLBCL developed severe infection, and subsequently KS. Our observations indicate that serious infections under rituximab treatment may trigger KS. KS should therefore be considered when skin tumors appear in lymphoma patients receiving rituximab containing chemotherapy. PMID- 26666615 TI - Clinical and Electron Microscopic Findings in Two Patients with Mitochondrial Myopathy Associated with Episodic Hyper-creatine Kinase-emia. AB - Mitochondrial myopathy with episodic hyper-creatine kinase (CK)-emia (MIMECK) is a new disease entity characterized by episodic or persistent muscle weakness and elevated CK levels. We herein report two cases of MIMECK with the findings of histopathological studies. Histopathological examinations revealed strongly succinate dehydrogenase-reactive vessels. Electron microscopy showed abnormal mitochondria in the vessels and proliferating and vacuolated mitochondria under the sarcolemma. Both patients exhibited recurrent severe myalgia, weakness and increased CK levels. L-arginine treatment significantly ameliorated their muscle symptoms. These findings indicate that mitochondrial angiopathy plays an important role in the pathophysiology of MIMECK. L-arginine may be a potential therapeutic agent for this disorder. PMID- 26666616 TI - Tocilizumab for AA Amyloidosis after Treatment of Multicentric Castleman Disease with Steroids, Chemotherapy and Rituximab for Over 20 Years. AB - We herein report the long-term outcome (30 years) of a human immunodeticiency virus- and human herpesvirus 8-negative Japanese man who was diagnosed to have multicentric Castleman disease (MCD) of the plasmacytic type after investigation of generalized lymphadenopathy at 34 of age in 1983. He received chemotherapy based on lymphoma regimens (combinations of prednisolone, vincristine, vindesine, cyclophosphamide, etoposide, melphalan, and ranimustine, etc.) for over 20 years. Although the systemic lymphadenopathy resolved, AA amyloidosis-related nephropathy occurred, with a serum creatinine (Cre) level of 0.9 mg/dL and urinary protein excretion (UP) of 7.5 g daily. Rituximab was started, but Cre increased to 2.6 mg/dL in 2010 and UP was unchanged. Therefore, treatment with tocilizmab was started. As a result, his hypergammaglobulinemia was well controlled, C-reactive protein became normal, UP decreased to 3.5 g daily, and Cre remained at 2.5 mg/dL in 2013. When AA amyloid nephropathy occurred after long-term chemotherapy, lituximab could not control it, but tocilizmab stopped the progression of nephropathy. This case suggests that MCD and AA amyloidosis may both have a close relationship to the overproduction of interleukin-6. PMID- 26666617 TI - Helicobacter cinaedi-associated Vertebral Osteomyelitis in an Immunocompetent Patient. AB - A 56-year-old previously healthy man was hospitalized due to a 10-day history of neck pain and an elevated C-reactive protein level. Gram-negative spiral bacilli were isolated from his blood, and Helicobacter cinaedi was confirmed using 16S rRNA sequencing. The infectious focus was not identified by initial cervical magnetic resonance imaging (MRI); however, repeated MRI demonstrated prominent high signal intensity in the entire region of the C6-C7 vertebrae and C6/C7 disc space. Furthermore, fluorodeoxyglucose-positron emission tomography/computed tomography showed no significant uptake, other than in the C6-C7 region. The patient was successfully treated with ceftriaxone for six weeks without sequelae. PMID- 26666618 TI - Pasteurella multocida Infective Endocarditis: A Possible Link with Primary Upper Respiratory Tract Infection. AB - A 50-year-old Japanese man presented with fever and upper respiratory tract symptoms that required urgent inpatient admission. A physical examination revealed conjunctival hemorrhages and peripheral embolic phenomena. Blood cultures grew Pasteurella multocida, and an echocardiography revealed a mitral valve vegetation suggestive of infective endocarditis (IE), which was confirmed using the Modified Duke Criteria. After several antibiotic regimens proved ineffective, valve replacement was performed, with a good eventual outcome. P. multocida IE is rare and may sometimes have no preceding risk factors. P. multocida infections of the upper respiratory tract are unusual but may be an inciting event for IE. It is essential to check blood cultures and to repeat the performance of physical examinations to appreciate the developing features of IE. PMID- 26666619 TI - A Nephrostomy-associated Urinary Tract Infection Caused by Elizabethkingia meningoseptica. AB - We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity. PMID- 26666620 TI - Escherichia coli Vertebral Osteomyelitis Diagnosed According to Broad-range 16S rRNA Gene Polymerase Chain Reaction (PCR). AB - Identifying the causative agent of pyogenic osteomyelitis is often challenging, especially when antibiotics are administered before a biopsy. We herein present a case of osteomyelitis in the cervical vertebrae presenting with progressive paralytic symptoms, in which we successfully identified Escherichia coli from a biopsy specimen using broad-range 16S rRNA gene polymerase chain reaction (PCR) even though sensitive antibiotics had been used for more than 50 days before the biopsy. Broad-range 16S rRNA gene PCR is a useful diagnostic method, especially when prebiopsy antibiotics are unavoidably used for a clinically unstable state. PMID- 26666621 TI - Intrapelvic Bulky Tumor as an Unusual Presentation of Erdheim-Chester Disease. AB - Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, which is known to affect various organs; however, there have been no reports of its intrapelvic involvement. We herein describe the case of 69-year old man who died of a rapidly-growing intrapelvic tumor, which was finally diagnosed as ECD at autopsy. Immunohistochemically, the tumor cells were positive for CD68 and BRAF V600E, and negative for CD1a. Since BRAF V600E has recently been reported to be specific to ECD, it can be a useful biomarker for diagnosis, especially in atypical cases. PMID- 26666622 TI - Angiotensin-converting-enzyme Inhibitor-induced Intestinal Angioedema. PMID- 26666623 TI - Different Vascular Reactions after "Hybrid Stenting". PMID- 26666624 TI - Giant Retroperitoneal Abscess Following Extracorporeal Shock Wave Lithotripsy. PMID- 26666625 TI - Optimal fall indicators for slip induced falls on a cross-slope. AB - Slip-induced falls are among the most common cause of major occupational injuries in the UK as well as being a major public health concern in the elderly population. This study aimed to determine the optimal fall indicators for fall detection models which could be used to reduce the detrimental consequences of falls. A total of 264 kinematic variables covering three-dimensional full body model translation and rotational measures were analysed during normal walking, successful recovery from slips and falls on a cross-slope. Large effect sizes were found for three kinematic variables which were able to distinguish falls from normal walking and successful recovery. Further work should consider other types of daily living activities as results show that the optimal kinematic fall indicators can vary considerably between movement types. Practitioner Summary: Fall detection models are used to minimise the adverse consequences of slip induced falls, a major public health concern. Optimal fall indicators were derived from a comprehensive set of kinematic variables for slips on a cross slope. Results suggest robust detection of falls is possible on a cross-slope but may be more difficult than level walking. PMID- 26666626 TI - Toward the Limits of Uniformity of Mixed Metallicity SWCNT TFT Arrays with Spark Synthesized and Surface-Density-Controlled Nanotube Networks. AB - We report the fabrication of thin film transistors (TFTs) from networks of nonbundled single-walled carbon nanotubes with controlled surface densities. Individual nanotubes were synthesized by using a spark generator-based floating catalyst CVD process. High uniformity and the control of SWCNT surface density were realized by mixing of the SWCNT aerosol in a turbulent flow mixer and monitoring the online number concentration with a condensation particle counter at the reactor outlet in real time. The networks consist of predominantly nonbundled SWCNTs with diameters of 1.0-1.3 nm, mean length of 3.97 MUm, and metallic to semiconducting tube ratio of 1:2. The ON/OFF ratio and charge carrier mobility of SWCNT TFTs were simultaneously optimized through fabrication of devices with SWCNT surface densities ranging from 0.36 to 1.8 MUm(-2) and channel lengths and widths from 5 to 100 MUm and from 100 to 500 MUm, respectively. The density optimized TFTs exhibited excellent performance figures with charge carrier mobilities up to 100 cm(2) V(-1) s(-1) and ON/OFF current ratios exceeding 1 * 10(6), combined with high uniformity and more than 99% of devices working as theoretically expected. PMID- 26666627 TI - Nucleobindin 1 (NUCB1) is a Golgi-resident marker of neurons. AB - Nucleobindin 1 (NUCB1; also known as CALNUC or NUC) is a putative DNA- and calcium-binding protein and exhibits significant structural homology with the protein nucleobindin 2 (NUCB2; also known as nesfatin). While NUCB2 has been mapped in detail in the brain and implicated in the hypothalamic control of energy metabolism, no study has to date addressed the presence of NUCB1 in the central nervous system. Here we have explored the expression and distribution of NUCB1 in the rat brain and spinal cord, using RT-PCR, immunofluorescence and in situ hybridization. NUCB1 mRNA and protein was found to be present in all brain regions, extending to the spinal cord and dorsal root ganglia. Double-staining for NUCB1 and NeuN, glial fibrillary acidic protein and myelin basic protein revealed that NUCB1 is exclusively found in neurons, and not in glial or ependymal cells. Notably, NUCB1-immunoreactivity was observed in all neurons examined, making no distinction between previously identified glutamatergic and GABAergic populations, including those that are known not to stain for NeuN. This included the markedly more restricted population of NUCB2-expressing neurons in the brain. The protein was detected in cell somata and proximal dendrites, but not in axons or terminal structures. Further examination of the subcellular distribution of NUCB1 using organelle-specific markers revealed its consistent presence in the Golgi apparatus. These findings identify NUCB1 as a novel pan neuronal marker. Along with the recent demonstration of broad expression of the protein in endocrine cells, the present results suggest that NUCB1 may play a role in spatiotemporal calcium handling in signaling cells. PMID- 26666629 TI - The prevalence of new psychoactive substances in biological material - a three year review of casework in Poland. AB - New psychoactive substances (NPS) pose a challenge for forensic and clinical toxicologists, as well as for legislators. We present our findings from cases where NPS have been detected in biological material. During the three-year period 2012-2014 we found NPS in 112 cases (out of 1058 analyzed), with 75 cases in 2014 alone. The prevalence of all NPS (15.1-17.6%) was similar to amphetamine alone that was detected in 15.1-16.5% of cases. The new drugs found belonged to the following classes: cathinones (88%), synthetic cannabinoids (5%), phenethylamines (3%), piperazines and piperidines (3%), arylalkylamines (1%) and other (1%). The drugs detected were (in the order of decreased frequency): 3-MMC (50), alpha pyrrolidinopentiophenone (alpha-PVP) (23), pentedrone (16), 3',4'-methylenedioxy alpha-pyrrolidinobutyrophenone (MDPBP) (12), synthetic cannabinoid UR-144 (7), ethcathinone (5), mephedrone (5), methylenedioxypyrovalerone (MDPV) (4), 4 methylethcathinone (4-MEC) (3), buphedrone (3), desoxypipradrol (2-DPMP) (3), methylone (2) and 2C-B (2). In single cases, 2-methylmethcathinone (2-MMC), 2C-P, eutylone, 25I-NBOMe, meta-chlorophenylpiperazine (mCPP), ephedrone, methiopropamine (MPA), and 5-(2-aminopropyl)benzofuran (5-APB) were found. One NPS was the sole agent in 35% of all cases, and two or more NPS were present in 19% of cases. NPS (one or more) with other conventional drugs (like amphetamines, cannabinoids, cocaine, and benzodiazepines) were detected in most (65%) of the cases. NPS were very often detected in the blood of drivers which was a challenge for toxicologists due to a lack of data on their influence on psychomotor performance. A review of concentrations showed a wide range of values in different types of cases, especially driving under the influence of drugs (DUID) and intoxication. PMID- 26666630 TI - Detection of Human Epididymis Protein 4 (HE4) in Human Serum Samples Using a Specific Monoclonal Antibody-Based Sandwich Enzyme-Linked Immunosorbent Assay (ELISA). AB - BACKGROUND: The human epididymis protein 4 (HE4) may have high specificity in the detection of malignant diseases, making the development of an immunoassay for HE4 essential. METHODS: In our study, a fusion gene was constructed encoded with the HE4 protein. This protein was then produced in the bacterial cells (Escherichia coli) and used to immunize mice in order to eventually generate hybridomas specific to HE4. The hybridoma supernatants were then screened, and four positive anti-HE4 cell lines were selected. These cell lines produce monoclonal antibodies against HE4 epitopes, as demonstrated in the Western blot as well as by direct enzyme-linked immunosorbent assay (ELISA). Using the developed antibodies, we successfully identified several good antibody pairs from the hybridomas, which allowed for the development of a sandwich ELISA to measure HE4 levels. By using the HE4 ELISA, we measured HE4 levels of 60 clinical human serum samples. RESULTS: Compared with the Food and Drug Administration (FDA) approved kit (Roche), our results showed a strong positive correlation to those of the FDA approved kit. CONCLUSIONS: In summary, highly sensitive antibody pairs were screened against HE4, and a sandwich ELISA was developed as an accurate analytical tool for the detection of HE4 in human serum, which could be especially valuable for diagnosing ovarian carcinomas. PMID- 26666631 TI - Sparing ultrasound in emergency department patients with suspected deep vein thrombosis by using clinical scores and D-dimer testing. AB - PURPOSE: To evaluate compliance with a management strategy for use in emergency department (ED) patients with suspected deep vein thrombosis (DVT) based on Wells score (WS), D-dimer concentrations, and sonographic (US) examinations. METHODS: Retrospective and prospective data on risk factors, physical examination findings, D-dimer concentrations, and US results were collected and reviewed. The prevalence of DVT for each WS category and D-dimer level was calculated. RESULTS: In the retrospective part of the study, 475 consecutive patients were included. Patients' risk for DVT was scored as high (n = 129 [27.2%]), moderate (n = 95 [20%]), or low (n = 251 [52.8%]). D-Dimer test results were available for 34 (7.2%) of the patients. DVT was diagnosed in 105 (22.1%) patients: 99 (76.7%) at high, 4 (4.2%) at moderate, and 2 (0.8%) at low risk. The mean D-dimer concentration was 3,071.7 ng/ml in patients with DVT. In the prospective part of the study, 50 patients were enrolled. Their risk levels for DVT were scored as high (n = 23 [46%]), moderate (n = 7 [14%]), and low (n = 20 [40%]). D-Dimer testing was performed in all patients. The mean D-dimer concentration was 2,966.9 ng/ml in patients with DVT. DVT was diagnosed in 13 (26%) of these 50 patients: 12 (52.2%) at high and 1 (14.3%) at moderate risk for DVT. No patients in the low risk group and with normal D-dimer concentrations had DVT. CONCLUSIONS: We identified significant correlation between WS, D-dimer concentration, and diagnosis of DVT on US examination. DVT can be excluded with certainty in patients admitted to the ED with a low-risk score for DVT and a negative D-dimer concentration, thus avoiding the need for performing US examinations. A low level of compliance with this management strategy was found in our ED. PMID- 26666634 TI - Versatile Oxidation Methods for Organic and Inorganic Substrates Catalyzed by Platinum-Group Metals on Carbons. AB - Platinum-group metals on activated carbon catalysts, represented by Pd/C, Ru/C, Rh/C, etc., are widely utilized to accomplish green and sustainable organic reactions due to their favorable features, such as easy handling, recoverability, and reusability. The efficient oxidation methods of various organic compounds using heterogeneous platinum-group metals on carbons with or without added oxidants are summarized in this Personal Account. The oxidation of internal alkynes into diketones was effectively catalyzed by Pd/C in the presence of dimethyl sulfoxide and molecular oxygen or pyridine N-oxide. The Pd/C-catalyzed mild combustion of gaseous hydrogen with molecular oxygen provided hydrogen peroxide, which could be directly utilized for the oxidation of sulfide derivatives into sulfoxides. Furthermore, the Ru/C-catalyzed aerobic oxidation of primary and secondary alcohols gave the corresponding aldehydes and ketones, respectively. On the other hand, the dehydrogenative oxidation of secondary alcohols into ketones was achieved using Rh/C in water, and primary alcohols were effectively dehydrogenated by Pd/C in water under mildly reduced pressure to produce carboxylic acids. PMID- 26666632 TI - Different subtype strains of Akkermansia muciniphila abundantly colonize in southern China. AB - AIM: This study investigates the colonization rate of Akkermansia muciniphila in the gastrointestinal tracts of people living in southern China and applies a modified method for the isolation and subtyping of A. muciniphila strains from faecal samples. METHODS AND RESULTS: Fresh faecal samples were collected and bacterial DNA was extracted from these samples for real-time PCR analysis. Strains were separated using a culture-dependent sPCR-directed method and classified using an enterobacterial repetitive intergenic consensus (ERIC-PCR) DNA fingerprinting method. The colonization rate for the sample population from southern China was 51.74%. We isolated 22 strains from human faeces. The results revealed that all strains were identifiable as A. muciniphila with 99-100% identity to the type-strain ATCC BAA-835. ERIC-PCR resulted in grouping of the DNA fingerprints showed that 12 distinct clusters were distinguished with a delineation level of 100%. CONCLUSIONS: Southern China has a high rate of A. muciniphila colonization and over 12 different subtype strains reside in faecal samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Akkermansia muciniphila has a beneficial role in human gastrointestinal tract. These studies provide a better understanding of A. muciniphila and details of its colonization in the human gastrointestinal tract. PMID- 26666633 TI - Risk factors associated with abscess formation among patient with leg erysipelas (cellulitis) in sub-Saharan Africa: a multicenter study. AB - BACKGROUND: Abscess formation is a frequent local complication of leg erysipelas. In this study we aimed at identifying factors associated with abscess formation of leg erysipelas in patients in sub-Saharan African countries. METHOD: This is a multicenter prospective study conducted in dermatology units in eight sub-Saharan African countries from October 2013 to September 2014. We performed univariate and multivariate analysis to compare characteristics among the group of patients with leg erysipelas complicated with abscess against those without this complication. RESULTS: In this study, 562 cases of leg erysipelas were recruited in the eight sub-Saharan African countries. The mean age of patients was 43.67 years (SD =16.8) (Range: 15 to 88 years) with a sex-ratio (M/F) of 5/1. Out of the 562 cases, 63 patients (11.2%) had abscess formation as a complication. In multivariate analysis showed that the main associated factors with this complication were: nicotine addiction (aOR = 3.7; 95 % CI = [1.3 - 10.7]) and delayed antibiotic treatment initiation (delay of 10 days or more) (aOR = 4.6; 95 % CI = [1.8 - 11.8]). CONCLUSION: Delayed antibiotics treatment and nicotine addiction are the main risk factors associated with abscess formation of leg erysipelas in these countries. However, chronic alcohol intake, which is currently found in Europe as a potential risk factor, was less frequent in our study. PMID- 26666635 TI - Permanent interstitial 125I seed implantation as a salvage therapy for pediatric recurrent or metastatic soft tissue sarcoma after multidisciplinary treatment. AB - BACKGROUND: The management of pediatric recurrent or metastatic soft tissue sarcoma after multimodal treatment remains challenging. We investigated the feasibility, efficacy, and morbidity of permanent interstitial (125)I seed implantation under image guidance as a salvage treatment for pediatric patients with recurrent or metastatic soft tissue sarcoma. METHODS: This was a retrospective study of 10 patients who underwent percutaneous ultrasound or computed tomography (CT) guided permanent (125)I seed implantation. Postoperative dosimetry was performed for all patients. Actuarial D90 was 121-187.1 Gy (median, 170.3 Gy). The number of (125)I seeds implanted was 6-158 (median, 34.5), with a median specific activity of 0.7 mCi per seed (range, 0.62-0.8 mCi); total activity was 4.2-113.76 mCi. Follow-up time was 6-107 months (median, 27.5 months); no patients were lost to follow-up. RESULTS: The overall response rate (complete response + partial response) was 8/10 (80 %), including two patients with complete response (CR) (20 %) and five patients with partial response (PR) (60 %). Local control rates after 1 and 2 years were 70.1 and 62.3 %, respectively, with a mean local control time of 70.6 months (95 % confidence interval (CI) 45.1-96.0). Survival rates after 1 and 2 years were 68.6 and 57.1 %, respectively, with a mean survival time of 65.3 months (95 % CI 34.1-96.5). Three patients died from distant metastasis; one died from local recurrence 12 months after seed implantation. Three patients suffered a grade I skin reaction and one developed ulceration. No severe adverse neurologic sequelae or blood vessel damage occurred. CONCLUSIONS: Image guided permanent interstitial (125)I seed implantation as a salvage treatment appears to have a satisfactory outcome in children with recurrent or metastatic soft tissue sarcoma. PMID- 26666637 TI - Erratum. PMID- 26666636 TI - Clinical manifestations and endoscopic findings of amebic colitis in a United States-Mexico border city: a case series. AB - BACKGROUND: Invasive amebiasis is not frequently seen in the United States. It is associated with considerable morbidity in patients residing in or traveling to endemic areas. We report a case series of patients with amebic colitis in a United States-Mexico border city to alert physicians to the varied clinical manifestations. CASE PRESENTATION: Nine patients were diagnosed with amebic colitis. Mean age was 56 (38-83), 6 were males, and all were Hispanic. Common symptoms were diarrhea (56 %), hematochezia (33 %) and abdominal bloating (11 %). The diagnosis of amebic colitis was established in the following ways: 8 patients by colonoscopy with biopsy, 1 by surgery for colonic obstruction. The diagnosis of amebic colitis was confirmed in 8 patients (89 %) by amebic trophozoites present in histopathologic sections. One patient was diagnosed with amebic colitis based upon clinical symptoms, colitis on colonoscopy and visualization of amebic trophozoites on stool examination. In the 8 patients in whom colonoscopy was done, 6 (75 %) had inflammation with rectosigmoid involvement and 5 (62.5 %) had ulcerations. Infection resolved after treatment with metronidazole in most patients; however, one patient developed a liver abscess and another had a colonic perforation and later developed a liver abscess. CONCLUSION: The occurrence of amebic colitis in this United States-Mexico border city hospital population was low, but in some cases potentially life-threatening. Physicians should be alert to the less common presentations of amebic colitis, such as overt gastrointestinal bleeding, exacerbation of inflammatory bowel disease, and the incidental finding of association with colon cancer, or a surgical abdomen. Rectosigmoid involvement was typically found on colonoscopy. PMID- 26666638 TI - Carotid Endarterectomy and Carotid Artery Stenting Lead to Improved Cognitive Performance in Patients with Severe Carotid Artery Stenosis. AB - In patients with severe carotid artery stenosis, the effects of carotid artery reopening, achieved either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), on cognitive functions remain elusive. Herein, we conducted a prospective study to determine whether and to what extent CEA and CAS affected cognitive performance. Patients admitted to the Department of Neurology or Vascular Surgery in Nanjing First Hospital from December 2012 to March 2015 with a diagnosis of severe carotid artery stenosis (>70%) were included in the study. Among them, 77 patients underwent CEA, 81 patients underwent CAS, and 77 patients who refused to receive aforementioned interventions were enrolled in control group. Of note, all patients in this study received basic pharmacological treatment according to the American Heart Association/American Stroke Association guidelines. Cognitive functions were evaluated by a broad spectrum of neuropsychological tests including the Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and event related potential P300 on the day prior to and at 3 months after indicated intervention. When compared with basic pharmacological treatment, both CEA and CAS significantly increased the scores of MMSE and MoCA at 3 months following procedures. Meanwhile, a significant reduction of P300 score was also observed in patients underwent CEA or CAS. In addition, the changes in MMSE, MoCA and P300 scores over time between CEA and CAS groups were not statistically significant. Taken together, our findings suggest an improvement of cognitive functions following carotid artery reopening. Meanwhile, the beneficial effects of CEA and CAS on cognitive performance seem to be equivalent. PMID- 26666639 TI - Cost-Effectiveness Modelling of Sofosbuvir-Containing Regimens for Chronic Genotype 5 Hepatitis C Virus Infection in South Africa. AB - BACKGROUND: The recently launched nucleotide polymerase inhibitor sofosbuvir represents a significant turn in the treatment paradigm of chronic hepatitis C. While effective, sofosbuvir is also associated with a considerable cost. OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of sofosbuvir-containing regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 5 (HCV-G5) mono-infection in South Africa (SA). DESIGN: We constructed a lifetime horizon decision-analytic Markov model of the natural history of HCV infection to evaluate the cost effectiveness of sofosbuvir ledipasvir (SOF/LDV) monotherapy against sofosbuvir triple therapy (SOF-TT) (sofosbuvir + pegylated interferon and ribavirin [peg-INF/RBV]) and the current standard of care (SOC) (peg-INF/RBV) for patients with chronic HCV-G5 in the South African context. The model was populated with data from published literature, expert opinion and South African private sector cost data. The price modelled for sofosbuvir was the predicted South African private sector price of 82,129.32 South African rand (R) (US$7000) for 12 weeks. The analysis was conducted from a third-party payer perspective. OUTCOME MEASURES: The outcome measures were discounted and undiscounted costs (in 2015 South African rand and US dollars) and quality-adjusted life-years (QALYs), and incremental cost effectiveness ratios (ICERs). RESULTS: Outcomes from the cost-effectiveness model show that SOF/LDV yields the most favourable future health economic outcomes compared with SOF-TT and the current SOC in SA. Findings relating to the lifetime incremental cost per QALY gained for patients infected with HCV-G5 indicate that SOF/LDV dominated both SOF-TT and SOC, i.e. SOF/LDV is less costly and more effective. CONCLUSION: Outcomes from this analysis suggest that at a price of R123,190 ($US10,500) for 12 weeks of SOF/LDV might be cost effective for South African patients infected with HCV-G5. PMID- 26666640 TI - The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3 Ubiquitin Ligase IDOL. AB - RATIONALE: The low-density lipoprotein (LDL) receptor (LDLR) is a central determinant of circulating LDL-cholesterol and as such subject to tight regulation. Recent studies and genetic evidence implicate the inducible degrader of the LDLR (IDOL) as a regulator of LDLR abundance and of circulating levels of LDL-cholesterol in humans. Acting as an E3-ubiquitin ligase, IDOL promotes ubiquitylation and subsequent lysosomal degradation of the LDLR. Consequently, inhibition of IDOL-mediated degradation of the LDLR represents a potential strategy to increase hepatic LDL-cholesterol clearance. OBJECTIVE: To establish whether deubiquitylases counteract IDOL-mediated ubiquitylation and degradation of the LDLR. METHODS AND RESULTS: Using a genetic screening approach, we identify the ubiquitin-specific protease 2 (USP2) as a post-transcriptional regulator of IDOL-mediated LDLR degradation. We demonstrate that both USP2 isoforms, USP2-69 and USP2-45, interact with IDOL and promote its deubiquitylation. IDOL deubiquitylation requires USP2 enzymatic activity and leads to a marked stabilization of IDOL protein. Paradoxically, this also markedly attenuates IDOL mediated degradation of the LDLR and the ability of IDOL to limit LDL uptake into cells. Conversely, loss of USP2 reduces LDLR protein in an IDOL-dependent manner and limits LDL uptake. We identify a tri-partite complex encompassing IDOL, USP2, and LDLR and demonstrate that in this context USP2 promotes deubiquitylation of the LDLR and prevents its degradation. CONCLUSIONS: Our findings identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. PMID- 26666641 TI - Risk Factors and Age-Related Macular Degeneration in a Mediterranean-Basin Population: The PAMDI (Prevalence of Age-Related Macular Degeneration in Italy) Study--Report 2. AB - AIM: To investigate the association of diet and other modifiable risk factors with the prevalence of age-related macular degeneration (ARMD) in rural and urban communities of a Mediterranean population in the northeast of Italy. METHODS: A cross-sectional population-based study was conducted among subjects aged over 60 years. A food frequency questionnaire (FFQ) was used to assess the consumption of different food categories, i.e., protective (P), risky (R), lutein-rich (L) and neutral (N). Smoking habit and alcohol intake were also examined. Macular pigment was measured by Raman spectroscopy. RESULTS: P food intake reduced the risk of large drusen (ARM2; OR 0.93; 95% CI 0.89-0.96) within the rural community. In this sub-group, R foods resulted in a slight association with large drusen, though the R/P food ratio was highly correlated with ARM2 (OR 1.21; 95% CI 1.12 1.31). Raman measures showed an age-dependent decrease but did not correlate with lutein intake. Smoking habit showed a positive association with ARM2 among women (OR 2.40; 95% CI 1.54-3.75), whereas alcohol consumption resulted in protective odds (OR 0.72; 95% CI 0.60-0.86). CONCLUSION: FFQ analysis confirmed the role of P and R foods and the benefit of a Mediterranean diet in ARMD. Moderate alcohol consumption showed a beneficial effect, whereas the deleterious role of a smoking habit was more evident in females. PMID- 26666642 TI - A simple method for identifying parameter correlations in partially observed linear dynamic models. AB - BACKGROUND: Parameter estimation represents one of the most significant challenges in systems biology. This is because biological models commonly contain a large number of parameters among which there may be functional interrelationships, thus leading to the problem of non-identifiability. Although identifiability analysis has been extensively studied by analytical as well as numerical approaches, systematic methods for remedying practically non identifiable models have rarely been investigated. RESULTS: We propose a simple method for identifying pairwise correlations and higher order interrelationships of parameters in partially observed linear dynamic models. This is made by derivation of the output sensitivity matrix and analysis of the linear dependencies of its columns. Consequently, analytical relations between the identifiability of the model parameters and the initial conditions as well as the input functions can be achieved. In the case of structural non-identifiability, identifiable combinations can be obtained by solving the resulting homogenous linear equations. In the case of practical non-identifiability, experiment conditions (i.e. initial condition and constant control signals) can be provided which are necessary for remedying the non-identifiability and unique parameter estimation. It is noted that the approach does not consider noisy data. In this way, the practical non-identifiability issue, which is popular for linear biological models, can be remedied. Several linear compartment models including an insulin receptor dynamics model are taken to illustrate the application of the proposed approach. CONCLUSIONS: Both structural and practical identifiability of partially observed linear dynamic models can be clarified by the proposed method. The result of this method provides important information for experimental design to remedy the practical non-identifiability if applicable. The derivation of the method is straightforward and thus the algorithm can be easily implemented into a software packet. PMID- 26666644 TI - Parliamentary privilege--mortality in members of the Houses of Parliament compared with the UK general population: retrospective cohort analysis, 1945 2011. AB - OBJECTIVE: To examine mortality in members of the two UK Houses of Parliament compared with the general population, 1945-2011. DESIGN: Retrospective cohort analysis of death rates and predictors of mortality in Members of Parliament (MPs) and members of the House of Lords (Lords). SETTING: UK. PARTICIPANTS: 4950 MPs and Lords first joining the UK parliament in 1945-2011. MAIN OUTCOME MEASURE: Standardised mortality ratios, comparing all cause death rates of MPs and Lords from first election or appointment with those in the age, sex, and calendar year matched general population. RESULTS: Between 1945 and 2011, mortality was lower in MPs (standardised mortality ratio 0.72, 95% confidence interval 0.67 to 0.76) and Lords (0.63, 0.60 to 0.67) than in the general population. Over the same period, death rates among MPs also improved more quickly than in the general population. For every 100 expected deaths, 22 fewer deaths occurred among MPs first elected in 1990-99 compared with MPs first elected in 1945-49. Labour party MPs had 19% higher death rates compared with the general population than did Conservative MPs (relative mortality ratio 1.19, 95% confidence interval 1.01 to 1.40). The effect of political party on mortality disappeared when controlling for education level. CONCLUSIONS: From 1945 to 2011, MPs and Lords experienced lower mortality than the UK general population, and, at least until 1999, the mortality gap between newly elected MPs and the general population widened. Even among MPs, educational background was an important predictor of mortality, and education possibly explains much of the mortality difference between Labour and Conservative MPs. Social inequalities are alive and well in UK parliamentarians, and at least in terms of mortality, MPs are likely to have never had it so good. PMID- 26666643 TI - Multicentric performance analysis of HCV quantification assays and its potential relevance for HCV treatment. AB - An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3* RealTime, 3* CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1-47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1-21.0 % and CTM v2: 15.0-32.3 %; CVs at 25 IU/ml: RealTime 17.6 34.9 % and CTM v2 28.2-54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR. PMID- 26666645 TI - A new animal model of intestinal mucositis induced by the combination of irinotecan and 5-fluorouracil in mice. AB - PURPOSE: Intestinal mucositis (IM) is a common side effect of anticancer agents. Despite polychemotherapy use in clinical practice, the pathogenesis of IM has been investigated in single drug injection animal models. However, the progression of IM could vary according to drug regimens. Thus, we aimed to develop a new experimental mucositis model induced by combining irinotecan and 5 fluorouracil (5-FU) treatments. METHODS: IM was induced in male C57BL/6 mice by the intraperitoneal administration of either 0.9 % saline (5 mL/kg), irinotecan (IRI, 30 or 45 mg/kg), 5-FU (25, 37.5, or 50 mg/kg), or the combination of these doses (IRI + 5-FU) for 4 days. Animal survival, body mass variation, and diarrhea scores were evaluated daily. On the 7th day, the mice were euthanized, and intestinal samples were collected for histopathology and morphometric analysis, as well as for the determination of myeloperoxidase activity and cytokine dosage (TNF-alpha and IL-6). RESULTS: The optimal dose combination that induced IM and presented no substantial mortality on the 7th day was IRI (45 mg/kg) + 5-FU (37.5 mg/kg), which was used for subsequent studies. IRI and 5-FU in combination induced significant diarrhea, body weight loss, intestinal damage, inflammatory cell infiltration, and increased levels of cytokines when compared with other groups (P < 0.05). Neither IRI nor 5-FU alone induced IM. CONCLUSIONS: We developed a new experimental model of IM induced by combining irinotecan and 5-FU treatments, which will allow us to gain a better knowledge concerning the pathogenesis of this disease through the pharmacological modulation of key inflammatory mediators. PMID- 26666646 TI - Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma. AB - PURPOSE: No standard salvage chemotherapy has been identified for metastatic pancreatic adenocarcinoma (mPA), and there is an urgent need for active agents against this disease. This phase II trial explored the activity of trabectedin in mPA progressing after gemcitabine-based first-line chemotherapy. METHODS: Patients with gemcitabine-resistant disease received trabectedin 1.3 mg/m(2) as a 3-h intravenous continuous infusion every 3 weeks until disease progression or unacceptable toxicity or for a maximum of 6 months. The primary endpoint was progression-free survival rate at 6 months (PFS-6). Since trabectedin modulates the production of selected inflammatory mediators, this study also aimed to identify inflammatory biomarkers predictive for response to trabectedin. RESULTS: Between February 2011 and February 2012, 25 patients received trabectedin. PFS-6 was 4%, median PFS 1.9 months (range 0.8-7.4), and median overall survival 5.2 months (range 1.1-24.3). Grade >2 toxicity consisted of neutropenia in 44% of patients, febrile neutropenia and thrombocytopenia both in 12%, anemia in 8%, fatigue in 12%, and AST and ALT increase in 8 and 4%, respectively. Trabectedin was shown to modulate the production of inflammatory mediators, and at disease progression, levels of a subgroup of cytokines/chemokines were modified. Furthermore, tissue analysis identified 30 genes associated with better prognosis. CONCLUSIONS: Although it has shown some ability to modulate inflammatory process, single-agent trabectedin had no activity as salvage therapy for mPA. PMID- 26666647 TI - Unique features of trabectedin mechanism of action. AB - Trabectedin (Yondelis(r), ET-743) is a marine-derived natural product that was initially isolated from the marine ascidian Ecteinascidia turbinata and is currently prepared synthetically. Trabectedin is used as a single agent for the treatment of patients with soft tissue sarcoma after failure of doxorubicin or ifosfamide or who are unsuited to receive these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin. Trabectedin presents a complex mechanism of action affecting key cell biology processes in tumor cells as well as in the tumor microenvironment. The inhibition of trans-activated transcription and the interaction with DNA repair proteins appear as a hallmark of the antiproliferative activity of trabectedin. Inhibition of active transcription is achieved by an initial direct mechanism that involves interaction with RNA polymerase II, thereby inducing its ubiquitination and degradation by the proteasome. This subsequently modulates the production of cytokines and chemokines by tumor and tumor-associated macrophages. Another interesting effect on activated transcription is mediated by the displacement of oncogenic transcription factors from their target promoters, thereby affecting oncogenic signaling addiction. In addition, it is well established that DNA repair systems including transcription-coupled nucleotide excision repair and homologous recombination play a role in the antitumor activity of trabectedin. Ongoing studies are currently addressing how to exploit these unique mechanistic features of trabectedin to combine this agent either with immunological or microenvironmental modulators or with classical chemotherapeutic agents in a more rational manner. PMID- 26666648 TI - In vitro characterization of transport and metabolism of the alkaloids: vincamine, vinpocetine and eburnamonine. AB - PURPOSE: Vincamine, vinpocetine and eburnamonine are alkaloids known for their neuroprotective attributes, enhancement of cerebrovascular blood flow and antitumor effect of their derivatives. However, the relative metabolic stability of these alkaloids and their extrusion by the drug efflux transporters expressed at the blood-brain barrier (BBB) are not clear. In this study, we developed rapid and sensitive methods for the detection of these alkaloids and investigated their relative metabolic stability and their interaction with drug efflux transporters. METHODS: UPLC methods were developed to analyze metabolic in vitro samples. Intrinsic clearance was determined using rat liver microsomal enzymes. Drug stimulated transporter activity was estimated by measuring inorganic phosphate released from ATP spectrophotometrically. RESULTS: The UPLC methods quantification level ranged from 0.02 to 0.025 ug/mL, indicating high sensitivity. The intrinsic clearance of eburnamonine was significantly less than both vincamine and vinpocetine. Different concentrations of the three drugs (4, 20 and 100 uM) induced minimal stimulation of the ATPase activity of the Bcrp and Pgp membrane transporters. CONCLUSIONS: The developed simple, sensitive and reliable UPLC analysis methods can be utilized in future in vitro and in vivo studies. The three alkaloids demonstrated minimal interaction with the drug efflux transporters Pgp and Bcrp, concordant with the ability of these alkaloids to cross the BBB. The relative metabolic stability of eburnamonine compared to the other alkaloids suggests the use of eburnamonine or its derivatives as lead compounds for the development of antitumor and nootropic agents that need to cross the BBB and produce their pharmacological effects in the CNS. PMID- 26666649 TI - International randomized phase 2 study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents. AB - PURPOSE: Nasopharyngeal carcinoma (NPC) is a rare but aggressive malignancy in children and adolescents. An international, randomized phase 2 trial was conducted to compare induction chemotherapy with docetaxel plus cisplatin and 5 fluorouracil (TPF) with cisplatin and 5-fluorouracil (PF) in NPC patients under the age of 21. METHODS: Patients with stage IIB-IV NPC were randomly assigned, in a 2:1 ratio, to receive TPF or PF 3-weekly for three cycles, followed by chemoradiotherapy. The primary endpoint was the complete response rate achieved with TPF or PF. Docetaxel pharmacokinetics was also evaluated. RESULTS: Seventy five patients (median 16 years old) were randomized, with 50 assigned to the TPF group and 25 to the PF group. Overall response was assessed after induction treatment: one patient in the TPF group and none in the PF group had a complete response. Partial response was achieved in 76.0 and 80.0 % in the TPF and PF groups, respectively. The overall safety profile was consistent with findings in adults. The estimated 3-year overall survival rate was 78.0 % for the PF group and 85.7 % for the TPF group (median follow-up 3.3 years). Mean docetaxel area under the curve was 3.41 ug h/mL, compared with 3.51 ug h/mL seen in adult patients. CONCLUSION: This study demonstrated the feasibility of prospective randomized protocols, even for such rare tumors as pediatric NPC. Overall, there were no differences between the two treatment arms in terms of efficacy and toxicity. The pharmacokinetics of docetaxel in pediatric patients at 75 mg/m(2) was similar to those observed in adults. PMID- 26666650 TI - Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes. AB - Brain tumor lacks effective delivery system for treatment. Focused ultrasound (FUS) can reversibly open BBB without impacts on normal tissues. As a potential drug carrier, cationic liposomes (CLs) have the ability to passively accumulate in tumor tissues for their positive charge. In this study, FUS introduced doxorubicin-loaded cationic liposomes (DOX-CLs) were applied to improve the efficiency of glioma-targeted delivery. Doxorubicin-loaded CLs (DOX-CLs) and quantum dot-loaded cationic liposomes (QD-CLs) were prepared using extrusion technology, and their characterizations were evaluated. With the advantage of QDs in tracing images, the glioma-targeted accumulation of FUS + CLs was evaluated by fluorescence imaging and flow cytometer. Cell survival rate, tumor volume, animal survival time, and brain histology in C6 glioma model were investigated to evaluate the glioma-targeted delivery of FUS + DOX-CLs. DOX-CLs and QD-CLs had suitable nanoscale sizes and high entrapment efficiency. The combined strategy of FUS introduced CLs significantly increased the glioma-targeted accumulation for load drugs. FUS + DOX-CLs showed the strongest inhibition on glioma based on glioma cell in vitro and glioma model in vivo experiments. From MRI and histological analysis, FUS + DOX-CLs group strongly suppressed the glioma progression and extended the animal survival time to 81.2 days. Among all the DOX treatment groups, FUS + DOX-CLs group showed the best cell viability and highest level of tumor apoptosis and necrosis. Combining the advantages of BBB reversible opening by FUS and glioma-targeted binding by CLs, ultrasound introduced cationic liposomes could achieve glioma-targeted delivery, which might be developed as a potential strategy for future brain tumor therapy. PMID- 26666651 TI - T Cell Fate at the Single-Cell Level. AB - T cell responses display two key characteristics. First, a small population of epitope-specific naive T cells expands by several orders of magnitude. Second, the T cells within this proliferating population take on diverse functional and phenotypic properties that determine their ability to exert effector functions and contribute to T cell memory. Recent technological advances in lineage tracing allow us for the first time to study these processes in vivo at single-cell resolution. Here, we summarize resulting data demonstrating that although epitope specific T cell responses are reproducibly similar at the population level, expansion potential and diversification patterns of the offspring derived from individual T cells are highly variable during both primary and recall immune responses. In spite of this stochastic response variation, individual memory T cells can serve as adult stem cells that provide robust regeneration of an epitope-specific tissue through population averaging. We discuss the relevance of these findings for T cell memory formation and clinical immunotherapy. PMID- 26666652 TI - ChromContact: A web tool for analyzing spatial contact of chromosomes from Hi-C data. AB - BACKGROUND: Hi-C analysis has revealed the three-dimensional architecture of chromosomes in the nucleus. Although Hi-C data contains valuable information on long-range interactions of chromosomes, the data is not yet widely utilized by molecular biologists because of the quantity of data. RESULTS: We developed a web tool, ChromContact, to utilize the information obtained by Hi-C. The web tool is designed to be simple and easy to use. By specifying a locus of interest, ChromContact calculates contact profiles and generates links to the UCSC Genome Browser, enabling users to visually examine the contact information with various annotations. CONCLUSION: ChromContact provides wide-range of molecular biologists with a user-friendly means to access high-resolution Hi-C data. One of the possible applications of ChromContact is investigating novel long-range promoter enhancer interactions. This facilitates the functional interpretation of statistically significant markers identified by GWAS or ChIP-seq peaks that are located far from any annotated genes. ChromContact is freely accessible at http://bioinfo.sls.kyushu-u.ac.jp/chromcontact/ . PMID- 26666656 TI - Snowballing citations. PMID- 26666655 TI - Trends in allergy prevalence among children aged 0-17 years by asthma status, United States, 2001-2013. AB - OBJECTIVES: Children with asthma and allergies--particularly food and/or multiple allergies-are at risk for adverse asthma outcomes. This analysis describes allergy prevalence trends among US children by asthma status. METHODS: We analyzed 2001-2013 National Health Interview Survey data for children aged 0-17 years. We estimated trends for reported respiratory, food, and skin allergy and the percentage of children with one, two, or all three allergy types by asthma status. We estimated unadjusted trends, and among children with asthma, adjusted associations between demographic characteristics and allergy. RESULTS: Prevalence of any allergy increased by 0.3 percentage points annually among children without asthma but not among children with asthma. However, underlying patterns changed among children with asthma: food and skin allergy prevalence increased as did the percentage with all three allergy types. Among children with asthma, risk was higher among younger and non-Hispanic black children for reported skin allergy, among non-Hispanic white children for reported respiratory allergy, and among non poor children for food and respiratory allergies. Prevalence of having one allergy type decreased by 0.50 percentage points annually, while the percent with all three types increased 0.2 percentage points annually. Non-poor and non Hispanic white children with asthma were more likely to have multiple allergy types. CONCLUSIONS: While overall allergy prevalence among children with asthma remained stable, patterns in reported allergy type and number suggested a greater proportion may be at risk of adverse asthma outcomes associated with allergy: food allergy increased as did the percentage with all three allergy types. PMID- 26666653 TI - Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness. AB - BACKGROUND: Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4 loading test, predictions of responsiveness according to the literature and types and locations of mutations. METHODS: A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. RESULTS: Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4 responsiveness and any other type of mutation predicts a negative response. CONCLUSIONS: This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients. PMID- 26666657 TI - Synthetic and reactivity studies of hetero-tri-anionic sodium zincates. AB - The synthesis and characterisation of several sodium zincate complexes are reported. The all-alkyl monomeric sodium zincate, (PMEDTA).Na(MU CH2SiMe3)Zn(t)Bu22, is prepared by combining equimolar quantities of (t)Bu2Zn, (n)BuNa and PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine)]. A similar approach was used to prepare and isolate the unusual dimeric zincate [(PMEDTA).Na(MU-(n)Bu)Zn(t)Bu2]23. When an equimolar mixture of (n)BuNa, (t)Bu2Zn and TMP(H) (2,2,6,6-tetramethylpiperidine) is combined in hexane, the hetero-tri leptic TMP(H)-solvated zincate (TMPH)Na(MU-TMP)(MU-(n)Bu)Zn(t)Bu 4 results. Complex 4 can also be prepared using a rational approach [i.e., utilising two molar equivalents of TMP(H)]. When TMEDA is reacted with an equimolar mixture of (n)BuNa, (t)Bu2Zn and TMP(H), the monomeric sodium zincate (TMEDA)Na(MU-TMP)(MU (n)Bu)Zn(t)Bu 5 was obtained - this complex is structurally similar to the synthetically useful relation (TMEDA).Na(MU-TMP)(MU-(t)Bu)Zn((t)Bu) 1. By changing the sodium reagent used in the synthesis of 5, it was possible to prepare (TMEDA)Na(MU-TMP)(MU-Me3SiCH2)Zn(t)Bu 6. By reacting 5 with cis-DMP(H) (cis-2,6-dimethylpiperidine), the zincate could thermodynamically function as an amide base, to give the transamination product (TMEDA)Na(MU-cis-DMP)(MU (n)Bu)Zn(t)Bu 7, although no crystals could be grown. However, when HMDS(H) (1,1,1,3,3,3-hexamethyldisilazane) or PEA(H) [(+)-bis[(R)-1-phenylethyl]amine] is reacted with 5, crystalline (TMEDA)Na(MU-HMDS)(MU-(n)Bu)Zn(t)Bu 8 or (TMEDA)Na(MU PEA)(MU-(n)Bu)Zn(t)Bu 9 is isolated respectively. With PNA(H) (N-phenylnaphthalen 1-amine) the reaction took a different course and resulted in the formation of the dimeric sodium amide complex [(TMEDA)Na(PNA)]210. When reacted with benzene, it appears that a TMEDA-free variant of 5 functions thermodynamically as an (n)Bu base to yield the previously reported (TMEDA)Na(MU-TMP)((t)Bu)Zn(MU C6H4)Zn((t)Bu)(MU-TMP)Na(TMEDA) 11. Finally when reacted with TEMPO (2,2,6,6 tetramethylpiperidinyloxy), 5 undergoes a single electron transfer reaction to form (TMEDA)Na(MU-TMP)(MU-TEMPO)Zn(n)Bu 12. PMID- 26666658 TI - Fast and simple procedure for fractionation of zinc in soil using an ultrasound probe and FAAS detection. Validation of the analytical method and evaluation of the uncertainty budget. AB - A new fast method for determination of mobile zinc fractions in soil is proposed in this work. The three-stage modified BCR procedure used for fractionation of zinc in soil was accelerated by using ultrasounds. The working parameters of an ultrasound probe, a power and a time of sonication, were optimized in order to acquire the content of analyte in soil extracts obtained by ultrasound-assisted sequential extraction (USE) consistent with that obtained by conventional modified Community Bureau of Reference (BCR) procedure. The content of zinc in extracts was determined by flame atomic absorption spectrometry. The developed USE procedure allowed for shortening the total extraction time from 48 h to 27 min in comparison to conventional modified BCR procedure. The method was fully validated, and the uncertainty budget was evaluated. The trueness and reproducibility of the developed method was confirmed by analysis of certified reference material of lake sediment BCR-701. The applicability of the procedure for fast, low costs and reliable determination of mobile zinc fraction in soil, which may be useful for assessing of anthropogenic impacts on natural resources and environmental monitoring purposes, was proved by analysis of different types of soil collected from Podlaskie Province (Poland). PMID- 26666659 TI - Evaluation of spatio-temporal variability in Land Surface Temperature: A case study of Zonguldak, Turkey. AB - The aim of this study is to analyze spatio-temporal variability in Land Surface Temperature (LST) in and around the city of Zonguldak as a result of the growing urbanization and industrialization during the last decade. Three Landsat 5 data and one Landsat 8 data acquired on different dates were exploited in acquiring LST maps utilizing mono-window algorithm. The outcomes obtained from this study indicate that there exists a significant temperature rise in the region for the time period between 1986 and 2015. Some cross sections were selected in order to examine the relationship between the land use and LST changes in more detail. The mean LST difference between 1986 and 2015 in ERDEMIR iron and steel plant (6.8 degrees C), forestland (3 degrees C), city and town centers (4.2 degrees C), municipal rubbish tip (-3.9 degrees C), coal dump site (12.2 degrees C), and power plants' region (7 degrees C) were presented. In addition, the results indicated that the mean LST difference between forestland and city centers was approximately 5 degrees C, and the difference between forestland and industrial enterprises was almost 8 degrees C for all years. Spatio-temporal variability in LST in Zonguldak was examined in that study and due to the increase in LST, policy makers and urban planners should consider LST and urban heat island parameters for sustainable development. PMID- 26666660 TI - Diabetes and Prior Coronary Heart Disease are Not Necessarily Risk Equivalent for Future Coronary Heart Disease Events. AB - BACKGROUND: For more than a decade, the presence of diabetes has been considered a coronary heart disease (CHD) "risk equivalent". OBJECTIVE: The objective of this study was to revisit the concept of risk equivalence by comparing the risk of subsequent CHD events among individuals with or without history of diabetes or CHD in a large contemporary real-world cohort over a period of 10 years (2002 to 2011). DESIGN: Population-based prospective cohort analysis. PARTICIPANTS: We studied a cohort of 1,586,061 adult members (ages 30-90 years) of Kaiser Permanente Northern California, an integrated health care delivery system. MAIN MEASUREMENTS: We calculated hazard ratios (HRs) from Cox proportional hazard models for CHD among four fixed cohorts, defined by prevalent (baseline) risk group: no history of diabetes or CHD (None), prior CHD alone (CHD), diabetes alone (DM), and diabetes and prior CHD (DM + CHD). KEY RESULTS: We observed 80,012 new CHD events over the follow-up period (~10,980,800 person-years). After multivariable adjustment, the HRs (reference: None) for new CHD events were as follows: CHD alone, 2.8 (95% CI, 2.7-2.85); DM alone 1.7 (95% CI, 1.66-1.74); DM + CHD, 3.9 (95% CI, 3.8-4.0). Individuals with diabetes alone had significantly lower risk of CHD across all age and sex strata compared to those with CHD alone (12.2 versus 22.5 per 1000 person-years). The risk of future CHD for patients with a history of either DM or CHD was similar only among those with diabetes of long duration (>=10 years). CONCLUSIONS: Not all individuals with diabetes should be unconditionally assumed to be a risk equivalent of those with prior CHD. PMID- 26666661 TI - Capsule Commentary on Peltz-Sinvani et al., Low ALT Levels Independently Associated with 22-Year All-Cause Mortality among Coronary Heart Disease Patients. PMID- 26666662 TI - Posterior Reversible Encephalopathy Syndrome After Transplantation: a Review. AB - Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease. Recently, an increase in the number of transplantations has led to more cases being associated with PRES than what was previously reported. Calcineurin inhibitors (CNIs) are major risk factors for PRES in posttransplantation patients. The mechanisms of the development of PRES remain to be unclear. The typical clinical symptoms of PRES include seizures, acute encephalopathy syndrome, and visual symptoms. The hyperintense signal on fluid-attenuated inversion recovery image is the characteristic of the imaging appearance in these patients. In addition, other abnormal signals distributed in multiple locations are also reported in some atypical cases. Unfortunately, PRES is often not recognized or diagnosed too late due to complicated differential diagnoses, such as ischemic stroke, progressive multifocal leukoencephalopathy, and neurodegenerative diseases. Thus, this review emphasizes the importance of considering the possibility of PRES when neurological disturbances appear after solid organ transplantation or hematopoietic cell transplantation. Moreover, this review demonstrates the molecular mechanisms of PRES associated with CNIs after transplantation, which aims to help clinicians further understand PRES in the transplantation era. PMID- 26666663 TI - Disruption of TCA Cycle and Glutamate Metabolism Identified by Metabolomics in an In Vitro Model of Amyotrophic Lateral Sclerosis. AB - This study aims to develop a cellular metabolomics model that reproduces the pathophysiological conditions found in amyotrophic lateral sclerosis in order to improve knowledge of disease physiology. We used a co-culture model combining the motor neuron-like cell line NSC-34 and the astrocyte clone C8-D1A, with each over expressing wild-type or G93C mutant human SOD1, to examine amyotrophic lateral sclerosis (ALS) physiology. We focused on the effects of mutant human SOD1 as well as oxidative stress induced by menadione on intracellular metabolism using a metabolomics approach through gas chromatography coupled with mass spectrometry (GC-MS) analysis. Preliminary non-supervised analysis by Principal Component Analysis (PCA) revealed that cell type, genetic environment, and time of culture influenced the metabolomics profiles. Supervised analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) on data from intracellular metabolomics profiles of SOD1G93C co-cultures produced metabolites involved in glutamate metabolism and the tricarboxylic acid cycle (TCA) cycle. This study revealed the feasibility of using a metabolomics approach in a cellular model of ALS. We identified potential disruption of the TCA cycle and glutamate metabolism under oxidative stress, which is consistent with prior research in the disease. Analysis of metabolic alterations in an in vitro model is a novel approach to investigation of disease physiology. PMID- 26666664 TI - The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain. AB - Isoprenylation is a posttranslational modification that transfers farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) to cysteine residues of a particular set of proteins, causing their localization to the plasma membrane and other cellular compartments and so rendering them biologically active. Such a modification process, catalyzed by protein prenyltransferase including farnesyltransferase (FT), geranylgeranyltransferase I (GGTI), and geranylgeranyltransferase II (GGTII), is required for the transforming activity of many oncogenic proteins, including some RAS family members. In the past three decades, prenyltransferase has been extensively studied as a promising cancer therapeutic target in vitro, in animal models, and in the clinic. Recently, a growing number of studies suggest that prenyltransferases and the substrates FPP and GGPP also play fundamental roles in nervous system development and brain disorders. However, a systemic review about the advances of prenyltransferases in the field of neuroscience is lacking so far. Herein, we give a brief introduction for the structure and distribution of GGTI and comprehensively updated the recent advances of GGTI in neuronal dendritogenesis/synaptogenesis and in learning/memory-related behavioral performance. More importantly, we discussed the involvement of GGTI and its substrate GGPP in neurodegenerative disorders, such as aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C. The role of FT-FPP and GGTII is mentioned as well to compare with GGTI in these physiological and pathological processes. We hope that this systematical review about what we know about GGTI research in the brain can stimulate further studies on the underlying mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders. PMID- 26666665 TI - Stem Cells in Neurotoxicology/Developmental Neurotoxicology: Current Scenario and Future Prospects. AB - Stem cell biology has played a pivotal role in the field of disease modeling, regenerative medicine, and tissue engineering. The scope of stem cell research has been further extended to address the issues associated with toxicity and biosafety. However, its role in the field of neurotoxicity (NT) and the emerging field of developmental neurotoxicity (DNT) is somewhat underrepresented and needs thorough investigation. Several challenges have hindered the progress of NT and DNT studies, and there is a dire need for human-specific high-throughput in vitro system(s) as a tool with better predictivity, reliability, and reproducibility. The unique proliferation and pluripotency of stem cells makes them a tremendous resource for human material, allowing the prediction of drug toxicity and metabolic effects of chemicals. Recognizing the growing importance of NT and DNT and the application of stem cell biology, in this review article, we provide the diversified approaches of stem cell research which can be effectively applied to the NT and DNT studies and provide an update of the recent progress made so far. We further provide a futuristic approach towards novel stem cell-based strategies for NT and DNT testing. We have further discussed the current technologies, role of induced pluripotent stem cells, the application of three-dimensional (3D) cultures and role of stem cell-derived organs in the NT and DNT studies. PMID- 26666666 TI - Angiotensin Receptor Blockade Modulates NFkappaB and STAT3 Signaling and Inhibits Glial Activation and Neuroinflammation Better than Angiotensin-Converting Enzyme Inhibition. AB - Neuroinflammation, sustained by astroglial and microglial activation, is the preceding event in neurodegeneration. Various clinical reports showed better neuroprotection by AT1 receptor blockade (ARB) than angiotensin-converting enzyme inhibition (ACEi), but experimental evidences and associated mechanism for this observation are lacking. Therefore, we investigated the effect of ARB, using Candesartan, and ACEi, using Perindopril, in equimolar concentrations in astroglial (C6) and microglial (BV2) cells employing lipopolysaccharide (LPS) to induce neuroinflammation. Further, Candesartan (0.1 mg/kg) and Perindopril (0.1 mg/kg) were orally administered in male SD rats for five consecutive days, and on the fifth day, rats were challenged with LPS (i.p.; 250 MUg/kg) and sacrificed after 24 h. LPS-induced neuroinflammation (increased astroglial and microglial activation, IkappaBalpha degradation, NFkB nuclear translocation, STAT3 activation, and TNF-alpha release) was more efficiently prevented by Candesartan (even at lower concentration of 1 nM) than by Perindopril (1 MUM) in both the cell types and in rat model of neuroinflammation. In addition, increased AT1 receptor (AT1R) and decreased AT2 receptor (AT2R) expression was observed in LPS induced neuroinflammation in both in vitro and in vivo studies. Candesartan, as compared to Perindopril, increased the expression of AT2R in both the experimental conditions. Interestingly, concomitant blockade of AT2R by PD123319 significantly reversed the beneficial effects of Candesartan in both the cell types and in rat model of neuroinflammation. Finally, our data emphasize that superiority of Candesartan as compared to Perindopril is due to better activation of AT2R which results in PP2A activation, IkappaBalpha stabilization, and suppression of NFkB and STAT3 inflammatory signaling. PMID- 26666669 TI - The role of anticoagulation in the management of pediatric temporal bone septic thrombophlebitis. PMID- 26666667 TI - Ibuprofen Induces Mitochondrial-Mediated Apoptosis Through Proteasomal Dysfunction. AB - In routine course of life, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed antipyretic, analgesic, and anti-inflammatory drugs. It is a well-proposed notion that treatment of NSAIDs may induce anti-proliferative effects in numerous cancer cells. Ibuprofen from isobutylphenylpropanoic acid is NSAID and used to relieve fever, pain, and inflammation. It is also used for juvenile idiopathic arthritis, rheumatoid arthritis, patent ductus arteriosus, and for pericarditis. Despite few emerging studies have expanded the fundamental concept that the treatment of NSAIDs influences apoptosis in cancer cells, however the NSAID-mediated precise mechanisms that determine apoptosis induction without producing adverse consequences in variety of cancer cells are largely unknown. In our present study, we have observed that ibuprofen reduces proteasome activity, enhances the aggregation of ubiquitylated abnormal proteins, and also elevates the accumulation of crucial proteasome substrates. Ibuprofen treatment causes mitochondrial abnormalities and releases cytochrome c into cytosol. Perhaps, the more detailed study is needed in the future to elucidate the molecular mechanisms of NSAIDs that can induce apoptosis without adverse effects and produce effective anti-tumor effects and consequently help in neurodegeneration and ageing. PMID- 26666670 TI - Optimized 4D time-of-flight MR angiography using saturation pulse. AB - PURPOSE: To assess arterial visibility on 4D time-of-flight (4D-TOF) by temporal magnetization transfer contrast pulse (t-MTC) and temporal tilted optimized nonsaturating excitation (t-TONE). 3D-TOF magnetic resonance angiography (MRA) is used for the noninvasive assessment of the intracranial arteries. However, it does not provide temporal information for diagnosing hemodynamics. To noninvasively obtain more detailed hemodynamics-related information, we developed a novel time-resolved MRA without the arterial spin labeling technique, termed 4D TOF MRA using saturation pulse. MATERIALS AND METHODS: On a 3.0T MRI, three techniques were compared to optimize the visibility of the arteries above the circle of Willis; 1) simple 4D-TOF, 2) 4D-TOF with t-MTC, and 3) 4D-TOF with t MTC and t-TONE. Eight healthy volunteers were scanned with these three sequences. The contrast changes between the background tissue and the arteries in temporal phases were assessed and compared quantitatively and qualitatively. RESULTS: The contrast between the background and the arteries for 4D-TOF with t-MTC and t-TONE was significantly higher than those for the other methods in delayed phases (P < 0.001).The qualitative assessment showed that 4D-TOF with t-MTC and with t-MTC and t-TONE provided better visualization of the intracranial artery than simple 4D-TOF (P < 0.001). CONCLUSION: 4D-TOF with t-TONE and t-MTC enabled observation of the intracranial hemodynamics. Optimized 4D-TOF provides high-quality images without image subtraction, and good visibility of the intracranial arteries even in the prolonged observation time. J. Magn. Reson. Imaging 2016;43:1320-1326. PMID- 26666668 TI - Corilagin Attenuates Radiation-Induced Brain Injury in Mice. AB - Cranial irradiation-induced inflammation plays a critical role in the initiation and progression of radiation-induced brain injury (RIBI). Anti-inflammation treatment may provide therapeutic benefits. Corilagin (beta-1-O-galloyl-3, 6-(R) hexahydroxydiphenoyl-D-glucose, C27H22O18) was a novel member of the tannin family with anti-inflammatory properties and is isolated from some medicinal plants, such as Phyllanthus amarus and Caesalpinia coriaria. In this study, the effect of Corilagin on RIBI was investigated and the underlying mechanisms were explored. Spatial learning and memory ability of mice were investigated by the Morris water maze test. Evans blue leakage and electron microscopy were used to assess the integrity of blood-brain barrier (BBB). The mRNA and protein expressions of inflammatory cytokines, TNF-alpha and IL-1beta, were measured by using real-time PCR and Western blotting. The activation of microglial cells and expression of TNF-alpha were examined by immunofluorescence staining. Phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and IkappaBalpha, and the translocation of p65 from cytoplasm to nucleus were detected by using Western blotting. Morris water maze test showed that Corilagin ameliorated the neurocognitive deficits in RIBI mice. Evans blue leakage and electron microscopy exhibited that Corilagin partially protected the BBB integrity from cranial irradiation-caused damage; immunofluorescence staining showed that Corilagin could inhibit microglial activation and TNF-alpha expression. Real-time PCR and Western blotting revealed that Corilagin downregulated the expression of TNF-alpha and IL-1beta and inhibited the irradiation-induced activation of NF-kappaB pathways by upregulating p-STAT3 expression. In conclusion, Corilagin could attenuate RIBI through inhibiting microglial activation and the expressions of inflammatory cytokines. Corilagin might inhibit the activation of NF-kappaB pathway in a STAT3-associated manner, thereby downregulating the inflammatory cytokine expressions. PMID- 26666671 TI - [Non-infectious unilateral wing lameness of pigeons, so called "Schieffliegersyndrom". First clinical and pathological results]. AB - OBJECTIVE: After medium- and long-distance flights and following the first training units of the year, a unilateral injuring of the shoulder joint is observed in racing pigeons. The objective of the study was to discuss the pathogenesis and aetiology of the damage. MATERIAL AND METHODS: In 35 pigeons suffering from unilateral wing lameness, the affected shoulder joints were examined microbiologically and histopathologically. Additionally, both shoulder joints of 12 affected pigeons were examined pathologically and histopathologically. RESULTS: Joint capsule, articular cartilage, tendons and bone structures displayed pathological changes. CONCLUSION: The non-infectious unilateral wing lameness of pigeons appears to be a stress-induced mechanical damage of the shoulder joint. The different structures of the joint are over extended by the physical/mechanical influences during longer flights. PMID- 26666673 TI - Dodecanuclear 3d/4f-metal clusters with a 'Star of David' topology: single molecule magnetism and magnetocaloric properties. AB - A family of interwoven molecular inorganic knots, shaped like the 'Star of David', was prepared by the employment of naphthalene-2,3-diol in 3d/4f-metal cluster chemistry; the isoskeletal dodecanuclear compounds exhibit slow relaxation of the magnetization and magnetocaloric properties, depending on the metal ion. PMID- 26666674 TI - The D-isoAsp-25 variant of histone H2B is highly enriched in active chromatin: potential role in the regulation of gene expression? AB - Approximately 12 % of histone H2B in mammalian brain contains an unusual D aspartate residue in its N-terminal tail. Most of this D-aspartate is linked to the C-flanking glycine via an isopeptide bond. To explore the possible significance of these modifications, we generated an antibody to the D isoaspartyl form of H2B, and used it to assess its levels in H2B associated with "active" vs. "silent" chromatin. We found that the D-isoaspartyl form of H2B appears to be highly enriched in the former. This irreversible modification could serve a novel regulatory function in gene expression. PMID- 26666676 TI - Intramedullary Fixation for Fractures of the Distal Fibula. PMID- 26666675 TI - Muscle and Joint Factors Associated With Forefoot Deformity in the Diabetic Neuropathic Foot. AB - BACKGROUND: Diabetic forefoot joint deformities are a known risk factor for skin breakdown and amputation, but the causes of deformity are not well understood. The purposes of this study were to determine the effects of intrinsic foot muscle deterioration and limited ankle joint mobility on the severity of metatarsophalangeal joint (MTPJ) deformity, and determine the relationships between these potential contributing factors and indicators of diabetic complications (peripheral neuropathy and advanced glycation end products). METHODS: A total of 34 participants with diabetic neuropathy (average age, 59 years; range 41-73) were studied. MTPJ angle and intrinsic foot muscle deterioration were measured with computed tomography and magnetic resonance imaging, respectively. Maximum ankle dorsiflexion was measured using kinematics. Skin intrinsic fluorescence served as a proxy measure for advanced glycation end product accumulation. RESULTS: Total forefoot lean muscle volume (r = -0.52, P < .01) and maximum ankle dorsiflexion (r = -0.42, P < .05) were correlated with severity of MTPJ deformity. Together they explained 35% of the variance of MTPJ angle. Neuropathy was correlated with forefoot muscle deterioration (rho = 0.53, P < .01). Skin intrinsic fluorescence was correlated to severity of neuropathy (r = 0.50, P < .01) but not maximum ankle dorsiflexion, or forefoot deterioration when controlling for neuropathy. CONCLUSION: These results suggest that the interplay of intrinsic foot muscle deterioration and limited ankle mobility may be the primary contributor to the development of MTPJ deformity. Identifying these muscle and ankle motion impairments as risk factors for MTPJ deformity supports the need for targeted interventions early in the disease process to slow, or possibly stop the progression of deformity over time and reduce the risk of amputation. LEVEL OF EVIDENCE: Level IV, case series. PMID- 26666677 TI - Radiographic Correction Following Reconstruction of Adult Acquired Flat Foot Deformity Using the Cotton Medial Cuneiform Osteotomy. AB - BACKGROUND: The Cotton osteotomy has been used to correct residual forefoot supination in flexible flatfoot deformity reconstruction. The purpose of this study was to delineate the radiographic effects of the Cotton osteotomy by controlling for concomitant procedures used for deformity correction. METHODS: We retrospectively analyzed 67 patients who underwent a Cotton osteotomy as part of a flatfoot reconstructive procedure. We evaluated 12 radiographic parameters including the articular surface angles of the foot, Meary angle, and a newly defined medial arch sag angle (MASA). Twenty-eight of these patients were matched to a cohort that did not undergo a Cotton osteotomy. RESULTS: In all patients who underwent a Cotton osteotomy, there were statistically significant changes in the articular surface angles and medial arch height (P < .05). No radiographic secondary sag of the medial column was seen at final follow-up. Compared to 28 matched controls, the Cotton osteotomy did not improve Meary angle but provided an additional 6.5 degrees correction of the MASA (P = .002). After reliability testing, the intraclass correlation coefficient was found to be substantial for the MASA compared to Meary angle. DISCUSSION: The data suggest that the MASA was a useful radiographic tool for assessing midfoot collapse in the setting of pes planovalgus. The current study demonstrated the corrective capacity of the Cotton osteotomy on the MASA; at final follow-up, there was no evidence of radiographic instability. This is suggestive that a naviculocuneiform arthrodesis may not be warranted for medial column stabilization in the setting of flatfoot reconstruction. LEVEL OF EVIDENCE: Level III, case control study. PMID- 26666678 TI - Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus. AB - BACKGROUND: Autologous osteochondral transplantation (AOT) is used to treat osteochondral lesions (OCLs) of the talus, typically reserved for lesions greater than 150 mm(2). Few studies exist examining the functional and magnetic resonance imaging (MRI) outcomes following this procedure. The purpose of this study was to investigate functional and MRI outcomes, including quantitative T2 mapping following AOT. METHODS: Eighty-five consecutive patients who underwent AOT were identified. Functional outcomes were assessed pre- and postoperatively using the Foot and Ankle Outcome Score (FAOS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was used to assess cartilage incorporation. Quantitative T2 MRI relaxation time of graft tissue and adjacent normal cartilage values were recorded in a subset of 61 patients. The mean clinical follow-up was 47.2 months, with mean MRI follow-up of 24.8 months. RESULTS: Mean FAOS improved pre- to postoperatively from 50 to 81 (P < .001). The mean MOCART score was 85.8. Lesion size was negatively correlated with MOCART score (r = -0.36, P = .004). Superficial T2 values in graft tissue were higher than control tissue (42.0 vs 35.8, P < .001). Deep T2 values in graft tissue were similar to the control values (30.9 vs 30.0, P = .305). Functional outcomes were similar in patients irrespective of whether they had previous microfracture or concomitant procedures. CONCLUSION: AOT was an effective treatment for large OCLs of the talus in the current study. MOCART scoring indicated good structural integrity of the graft. Quantitative T2 mapping suggests that graft tissue may not always mirror native hyaline cartilage. The long-term implications of this are not yet known. LEVEL OF EVIDENCE: Level IV, case series. PMID- 26666679 TI - Two new benzolactones from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities. AB - Two new benzolactones, 5-methyl-6-prenyl-isobenzofuran-1(3H)-one (1), 5 hydroxymethyl-6-prenyl-isobenzofuran-1(3H)-one (2), together with four known phenolic compounds (3-6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 1-6 exhibited high anti-TMV activities with inhibition rates in the range of 16.9-26.2%, respectively. PMID- 26666680 TI - Co-Creating a Culturally Responsive Distance Education Cancer Course with, and for, Alaska's Community Health Workers: Motivations from a Survey of Key Stakeholders. AB - To gain input on a proposed culturally responsive, distance-delivered cancer education course informed by empowerment theory and adult-learning principles, Alaska's Community Health Aides/Practitioners (CHA/Ps) and CHA/P leadership were invited to take an online survey in February 2015. The proposed course will be developed as part of the "Distance Education to Engage Alaskan Community Health Aides in Cancer Control" project. The results of the survey demonstrate that respondents are both interested in taking the proposed class and engaging in course development. The results also indicate that respondents have the technological comfort and capacity to be engaged in online learning and have primarily positive experiences and perceptions of distance education. This survey is the beginning of the interactive development of the online cancer education course and part of a continuing endeavor to promote wellness with, and for, Alaska's people by empowering Alaska's CHA/Ps and inspiring positive behavioral change to both prevent cancer and support those who feel its burdens. PMID- 26666682 TI - Well-constructed silicon-based materials as high-performance lithium-ion battery anodes. AB - Silicon has been considered as one of the most promising anode material alternates for next-generation lithium-ion batteries, because of its high theoretical capacity, environmental friendliness, high safety, low cost, etc. Nevertheless, silicon-based anode materials (especially bulk silicon) suffer from severe capacity fading resulting from their low intrinsic electrical conductivity and great volume variation during lithiation/delithiation processes. To address this challenge, a few special constructions from nanostructures to anchored, flexible, sandwich, core-shell, porous and even integrated structures, have been well designed and fabricated to effectively improve the cycling performance of silicon-based anodes. In view of the fast development of silicon-based anode materials, we summarize their recent progress in structural design principles, preparation methods, morphological characteristics and electrochemical performance by highlighting the material structure. We also point out the associated problems and challenges faced by these anodes and introduce some feasible strategies to further boost their electrochemical performance. Furthermore, we give a few suggestions relating to the developing trends to better mature their practical applications in next-generation lithium-ion batteries. PMID- 26666681 TI - Distinct promoter activation mechanisms modulate noise-driven HIV gene expression. AB - Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a 'molecular switch' controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance. PMID- 26666683 TI - Evaluation of CDC light traps for mosquito surveillance in a malaria endemic area on the Thai-Myanmar border. AB - BACKGROUND: Centers for Disease Control and Prevention miniature light traps (CDC LT) baited with CO2 are a routine tool for adult mosquito sampling used in entomological surveys, and for monitoring and surveillance of disease vectors. The present study was aimed at evaluating the performance of baited and unbaited CDC-LT for indoor and outdoor trapping of endemic mosquito species in northwestern Thailand. METHODS: CDC-LT (n = 112) with and without dry ice baits were set both indoors and outdoors in 88 selected houses for stretches of 5 consecutive nights per month in 7 villages in Tha Song Yang district, Tak province between January 2011 and March 2013. Individual traps were repeatedly placed in the same location for a median of 6 (range 1-10) times. Mosquitoes were identified by morphological characteristics and classified into blood-fed, empty, male/female and gravid. Absolute mosquito numbers were converted to capture rates (i.e., mosquitoes per trap and year). Capture rates were compared using multilevel negative binomial regression to account for multiple trap placements and adjust for regional and seasonal differences. RESULTS: A total of 6,668 mosquitoes from 9 genera were collected from 576 individual CDC-LT placements. Culex was the predominant captured genus (46%), followed by anopheline mosquitoes (45%). Overall, CO2 baited traps captured significantly more Culex (especially Culex vishnui Theobald) and Anopheles mosquitoes per unit time (adjusted capture rate ratio (aCRR) 1.64 and 1.38, respectively). Armigeres spp. mosquitoes were trapped in outdoor traps with significantly higher frequency (aCRR: 1.50), whereas Aedes albopictus (Skuse) had a tendency to be trapped more frequently indoors (aCRR: 1.89, p = 0.07). Furthermore, capture rate ratios between CO2 baited and non-baited CDC-LT were significantly influenced by seasonality and indoor vs. outdoor trap placement. CONCLUSION: The present study shows that CDC LT with CO2 baiting capture significantly more Culex and Anopheles mosquitoes, some of which (e.g., Cx. vishnui, Cx. quinquefasciatus Say, An. minimus s.l. Theobald, An. maculatus s.l. Theobald) represent important disease vectors in Thailand. This study also shows significant differences in the capture efficiency of CDC-LT when placed indoors or outdoors and in different seasons. Our study thus provides important guidelines for more targeted future vector trapping studies on the Thai-Myanmar border, which is an important cross-border malaria transmission region in Thailand. PMID- 26666684 TI - An epidemiological study to investigate the relationship between Meniere's disease and migraine. AB - OBJECTIVES: A relationship between Meniere's disease and migraine has been postulated previously. This study investigates this relationship further and determines the most influential factors for developing Meniere's disease. DESIGN: Epidemiological study. SETTING: Two tertiary referral Neuro-Otological centres in Sheffield and Sydney. PARTICIPANTS: Adult patients referred to the Neuro-Otology clinic between 2003 and 2010. MAIN OUTCOME MEASURES: Past history and family history of Meniere's disease and migraine. Logistic regression analysis to determine the most influential factors for Meniere's disease. RESULTS: One hundred and eighty-one patients were included in the study, 102 with Meniere's disease and 79 with other balance disorders. Three significant findings were demonstrated. Firstly, a family history of Meniere's disease (33.3% versus 6.3%) or migraine (21.6% versus 9%) is more common in the Meniere's disease group than in the other balance disorders group. Secondly, a history of migrainous headaches is more common in the Meniere's disease group than in the other balance disorders group (45.1% versus 9%). Thirdly, patients with a past history or a family history of Meniere's disease or migraine have a higher likelihood of suffering from Meniere's disease. CONCLUSIONS: There is an overall relationship between Meniere's disease and migraine. A family history of Meniere's disease or migraine is more common in Meniere's disease. A history of migrainous headache is more common in Meniere's disease. Patients with a past history or family history of Meniere's disease or migraine have a higher likelihood of suffering from Meniere's disease. PMID- 26666685 TI - Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes. AB - The natural cytotoxicity receptors NKp46/NCR1, NKp44/NCR2 and NKp30/NCR3 are critical for natural killer (NK) cell functions. Their genes are transcribed into several splice variants whose physiological relevance is not yet fully understood. Here we report that decidua basalis NK (dNK) cells of the pregnant uterine mucosa and peripheral blood NK (pNK) cells, two functionally distinct subsets of the physiological NK cell pool, display differential expression of NKp30/NCR3 and NKp44/NCR2 splice variants. The presence of cytokines that are enriched within the decidual microenvironment is sufficient to convert the splice variant profile of pNK cells into one similar to that of dNK cells. This switch is associated with decreased cytotoxic function and major adaptations to the secretome, hallmarks of the decidual phenotype. Thus, NKp30/NCR3 and NKp44/NCR2 splice variants delineate functionally distinct NK cell subsets. To our knowledge, this is the first conclusive evidence underlining the physiological importance of NCR splice variants. PMID- 26666686 TI - Allosteric stabilization of the amyloid-beta peptide hairpin by the fluctuating N terminal. AB - Immobilized ions modulate nearby hydrophobic interactions and influence molecular recognition and self-assembly. We simulated disulfide bond-locked double mutants (L17C/L34C) and observed allosteric modulation of the peptide's intra-molecular interactions by the N-terminal tail. We revealed that the non-contacting charged N-terminal residues help the transfer of entropy to the surrounding solvation shell and stabilizing beta-hairpin. PMID- 26666687 TI - Making sense of self in Alzheimer's disease: reflective function and memory. AB - OBJECTIVE: The current investigation examined the relationship between cognitive impairment and sense of self in Alzheimer's disease (AD). METHOD: Forty-nine participants with dementia associated with AD were recruited through memory clinics in Victoria, Australia. The 26 participants of the healthy control sample were recruited from a retirement village. Self was measured via the Reflective Self-Function Scale - a theory of mind indicator that provides personal and social self-reflection scores. Cognitive assessment included measures of new learning, executive function, and speed of information processing. RESULTS: A reduction in sense of self in mild AD was demonstrated in both personal and social domains, as compared to healthy adults of a similar age. With a focus on specific cognitive impairment relationships, new learning was found to predict personal self-reflection, whereas speed of information processing predicted social self-reflection capacity. CONCLUSION: Findings suggest that deficits in new learning ability contribute to a reduced ability of people with early AD to understand their mental world and interpret thoughts, feelings, and beliefs about themselves. This impaired capacity to self-reflect will be intrusive in daily activities that require monitoring of current self-performance. Furthermore, with reduced speed of information processing found to impact on ability to reflect on social relations, individuals with AD are placed at risk of reduced ability to understand their social world, including communicating and interacting with others. Notwithstanding the overall group findings, individual variability was evident which reinforces the need for person-centred care in dementia. PMID- 26666688 TI - Efficacy of a self-help manual in increasing resilience in carers of adults with depression in Thailand. AB - Caring for a person with a mental illness can have adverse effects on caregivers; however, little is known about how best to help such caregivers. The aim of the present study was to examine the efficacy of a cognitive behaviour therapy-guided self-help manual in increasing resilience in caregivers of individuals with depression, in comparison to caregivers who receive routine support only. A randomized, controlled trial was conducted, following CONSORT guidelines, with 54 caregivers allocated to parallel intervention (self-help manual) (n = 27) or control (standard support) (n = 27) groups. Resilience was assessed at baseline, post-test (week 8), and follow up (week 12). Intention-to-treat analyses were undertaken. Repeated-measures ANOVA indicated a significant difference in resilience scores between the three time points, showing a large effect. Pairwise comparisons between intervention and control groups indicated resilience to be significantly different between baseline and post-test, and between baseline and follow up, but not between post-test and follow up. Overall, the intervention group showed a slightly greater increase in resilience over time than the control group; however, the time-group interaction was not significant. Guided self-help is helpful in improving caregivers' resilience and could be used as an adjunct to the limited support provided to carers by mental health nurses and other clinicians. PMID- 26666689 TI - Influences of radiation on carp from farm ponds in Fukushima. AB - A massive release of artificial radionuclides from the Fukushima Dai-ichi Nuclear Power Plant caused radioactive contamination of farms as well as of aquatic products. Carp in small ponds in the highly radiocontaminated area of Iitate Village, Fukushima Prefecture, have been confined to the ponds since the accident, and it is thought that the carp may have suffered health issues as a result. Therefore, I investigated the health condition of the carp in order to elucidate the effects of radiation.Blood neutrophil, monocyte and lymphocyte counts in the carp from three ponds in Fukushima were lower than those in carp from a non-polluted pond in Tochigi Prefecture. Histological observations indicated abnormal hyperplasia of macrophages in the spleen, kidney, liver and pancreas of carp in Fukushima. Although there are likely to have been deleterious effects on carp health due to the radiation in Fukushima, this has not yet been confirmed because only one control pond was available for comparison, and I was not able to find any symptoms in the carp that correlated with internal cesium concentration. Further research is now being conducted to investigate the effects of radiation on carp. PMID- 26666690 TI - In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage. AB - XRCC4 is a protein associated with DNA Ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non homologous end joining. In response to treatment with ionizing radiation or DNA damaging agents, XRCC4 undergoes DNA-PK-dependent phosphorylation. Furthermore, Ser260 and Ser320 (or Ser318 in alternatively spliced form) of XRCC4 were identified as the major phosphorylation sites by purified DNA-PK in vitro through mass spectrometry. However, it has not been clear whether these sites are phosphorylated in vivo in response to DNA damage. In the present study, we generated an antibody that reacts with XRCC4 phosphorylated at Ser320 and examined in cellulo phosphorylation status of XRCC4 Ser320. The phosphorylation of XRCC4 Ser320 was induced by gamma-ray irradiation and treatment with Zeocin. The phosphorylation of XRCC4 Ser320 was detected even after 1 Gy irradiation and increased in a manner dependent on radiation dose. The phosphorylation was observed immediately after irradiation and remained mostly unchanged for up to 4 h. The phosphorylation was inhibited by DNA-PK inhibitor NU7441 and was undetectable in DNA-PKcs-deficient cells, indicating that the phosphorylation was mainly mediated by DNA-PK. These results suggested potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells. PMID- 26666691 TI - The extremely broad odorant response profile of mouse olfactory sensory neurons expressing the odorant receptor MOR256-17 includes trace amine-associated receptor ligands. AB - The mouse olfactory system employs ~1100 G-protein-coupled odorant receptors (ORs). Each mature olfactory sensory neuron (OSN) is thought to express just one OR gene, and the expressed OR determines the odorant response properties of the OSN. The broadest odorant response profile thus far demonstrated in native mouse OSNs is for OSNs that express the OR gene SR1 (also known as Olfr124 and MOR256 3). Here we showed that the odorant responsiveness of native mouse OSNs expressing the OR gene MOR256-17 (also known as Olfr15 and OR3) is even broader than that of OSNs expressing SR1. We investigated the electrophysiological properties of green fluorescent protein (GFP)+ OSNs in a MOR256-17-IRES-tauGFP gene-targeted mouse strain, in parallel with GFP+ OSNs in the SR1-IRES-tauGFP gene-targeted mouse strain that we previously reported. Of 35 single chemical compounds belonging to distinct structural classes, MOR256-17+ OSNs responded to 31 chemicals, compared with 10 for SR1+ OSNs. The 10 compounds that activated SR1+ OSNs also activated MOR256-17+ OSNs. Interestingly, MOR256-17+ OSNs were activated by three amines (cyclohexylamine, isopenthylamine, and phenylethylamine) that are typically viewed as ligands for chemosensory neurons in the main olfactory epithelium that express trace amine-associated receptor genes, a family of 15 genes encoding G-protein-coupled receptors unrelated in sequence to ORs. We did not observe differences in membrane properties, indicating that the differences in odorant response profiles between the two OSN populations were due to the expressed OR. MOR256-17+ OSNs appear to be at one extreme of odorant responsiveness among populations of OSNs expressing distinct OR genes in the mouse. PMID- 26666692 TI - Graphene flakes under controlled biaxial deformation. AB - Thin membranes, such as monolayer graphene of monoatomic thickness, are bound to exhibit lateral buckling under uniaxial tensile loading that impairs its mechanical behaviour. In this work, we have developed an experimental device to subject 2D materials to controlled equibiaxial strain on supported beams that can be flexed up or down to subject the material to either compression or tension, respectively. Using strain gauges in tandem with Raman spectroscopy measurements, we monitor the G and 2D phonon properties of graphene under biaxial strain and thus extract important information about the uptake of stress under these conditions. The experimental shift over strain for the G and 2D Raman peaks were found to be in the range of 62.3 +/- 5 cm(-1)/%, and 148.2 +/- 6 cm(-1)/%, respectively, for monolayer but also bilayer graphenes. The corresponding Gruneisen parameters for the G and 2D peaks were found to be between 1.97 +/- 0.15 and 2.86 +/- 0.12, respectively. These values agree reasonably well with those obtained from small-strain bubble-type experiments. The results presented are also backed up by classical and ab initio molecular dynamics simulations and excellent agreement of Gamma-E2g shifts with strains and the Gruneisen parameter was observed. PMID- 26666693 TI - Risk evaluation for needle-nerve contact related to electrical nerve stimulation in a porcine model. AB - BACKGROUND: For performing peripheral nerve blocks, the risk for needle-nerve contact (NNC) as an adverse event for low and high current thresholds has not yet been clearly defined when nerve stimulator guided techniques were applied. This experimental study aimed to investigate the risk of NNCs when applying stimulation currents between 0.1 and 2 mA (in increments of 0.1 mA). METHODS: Brachial plexus nerves were exposed surgically in five anesthetized pigs. An insulated needle connected to a nerve stimulator was placed at 10 mm distance to the targeted nerves. Current intensity was adjusted according to randomization (0.1-2.0 mA, increments of 0.1 mA). The needle tip was advanced toward the nerve until a motor response was elicited. The frequencies of NNCs for each of the adjusted current intensities were noted. Risks of NNCs were calculated according to the analysis of 95% confidence intervals (95% CI). RESULTS: We executed 2000 needle placements with stimulation currents ranging from 0.1 to 2.0 mA. The risks for NNC at low current intensities were 0.85 (95% CI, 0.77-0.91) for 0.3 mA and 0.5 (95% CI, 0.4-0.6) for 0.5 mA, respectively. For high current intensities, risks of 0.13 (95% CI, 0.07-0.21) for 0.9 mA and 0.01 (95% CI, 0-0.05) for 1.1 mA were calculated. CONCLUSIONS: In this experimental animal study, a relevant reduction in the risk of NNCs could be observed when high current intensities (0.9-1.1 mA) were applied compared to low current intensities (0.3-0.5 mA). PMID- 26666694 TI - Sense of community coherence and inter-religious relations. AB - The current article attempts to broaden the individual-based concept of sense of coherence to the community level. We examine sense of community coherence and its connection with perceptions of collective narratives and acculturation tendencies in the social context of Palestinian Muslims and Christians living in Israel. Questionnaires that were developed and adapted for the unique population in this study were distributed to a representative sample of 1034 Muslims (455 males) and 720 Christians (354 males), all Israeli citizens aged 18 and up. As expected, sense of community coherence was negatively related to the level of acceptance of the out-group collective narratives and positively related to the level of acceptance of the in-group collective narratives. In the same vein, it was also positively related to the tendency for separation and negatively related to the tendency for integration and assimilation. The discussion focuses on the contribution of the research findings to the deepening of our understanding of the concepts of sense of coherence and sense of community coherence. PMID- 26666695 TI - Preliminary evidence for association of genome-wide significant DRD2 schizophrenia risk variant with clozapine response. AB - AIM: The recent Psychiatric Genomics Consortium genome-wide association study identified an SNP, rs2514218, located 47kb upstream of the DRD2 gene to be associated with risk for schizophrenia (p = 2.75e-11). Since all antipsychotics bind to dopamine D2 receptors, we examined rs2514218 in relation to response to antipsychotic treatment. PATIENTS & METHODS: We investigated the SNP in relation to treatment response in a prospective study consisting of 208 patients (151 Caucasians, 42 African-Americans and 15 others) treated with clozapine for 6 months. RESULTS: rs2514218 was associated with total score change in the brief psychiatric rating scale under an additive model (pcorr= 0.033). CONCLUSION: Our finding provides evidence for rs2514218 association with antipsychotic response, but further replication is required before firm conclusions can be drawn. PMID- 26666696 TI - 'He's got his father's bias': Parental influence on weight bias in young children. AB - Our aim was to explore the role of parents in the transmission of stereotypical body size attitudes and awareness of weight loss strategies to preschool children. Participants were 279 3-year-old children and their parents, who provided data at baseline and 1 year later. Parents completed self-report body size attitude and dieting measures. Child weight bias and awareness of weight loss strategies were assessed through interview. Over time, negative associations with large bodies and awareness of weight loss strategies increased. Fathers' attitudes prospectively predicted boys' weight bias and awareness of weight loss strategies. Among girls, parental attitudes were less predictive. Findings confirm the importance of fathers in the development of boys' body attitudes and inform prevention programmes. PMID- 26666697 TI - Defect-Free Self-Catalyzed GaAs/GaAsP Nanowire Quantum Dots Grown on Silicon Substrate. AB - The III-V nanowire quantum dots (NWQDs) monolithically grown on silicon substrates, combining the advantages of both one- and zero-dimensional materials, represent one of the most promising technologies for integrating advanced III-V photonic technologies on a silicon microelectronics platform. However, there are great challenges in the fabrication of high-quality III-V NWQDs by a bottom-up approach, that is, growth by the vapor-liquid-solid method, because of the potential contamination caused by external metal catalysts and the various types of interfacial defects introduced by self-catalyzed growth. Here, we report the defect-free self-catalyzed III-V NWQDs, GaAs quantum dots in GaAsP nanowires, on a silicon substrate with pure zinc blende structure for the first time. Well resolved excitonic emission is observed with a narrow line width. These results pave the way toward on-chip III-V quantum information and photonic devices on silicon platform. PMID- 26666698 TI - Determinants of Anemia Among Human Immunodeficiency Virus-Positive Adults at Care and Treatment Clinics in Dar es Salaam, Tanzania. AB - Anemia is often a comorbidity of human immunodeficiency virus (HIV) infection. Many cross-sectional studies have been conducted on anemia and HIV, but few, if any, have addressed incidence of anemia prospectively. A longitudinal analysis was conducted in 48,068 nonpregnant HIV-infected adults in Dar es Salaam, Tanzania, seen at Management and Development for Health-U.S. President's Emergency Plan for AIDS Relief HIV care and treatment programs between 2004 and 2011. Almost 56% (N = 27,184) of study participants had anemia (hemoglobin < 11 g/dL) at the time of enrollment at the clinic. Female gender, low body mass index (BMI), low CD4 T-cell count, high levels of liver enzyme alanine aminotransferase, antiretroviral treatment (ART) regimens, and concurrent tuberculosis treatment were all independently significantly associated with an increased risk of anemia. Low BMI and low CD4 T-cell count were independently significantly associated with an increased risk for iron deficiency anemia (IDA). Higher BMI status and ART use were associated with recovery from anemia. Anemia, including IDA, is a comorbidity that is associated with other adverse consequences (e.g., low BMI and CD4 T-cell count) among individuals with HIV infection, including those on ART. Interventions to prevent anemia and its complications need to be examined in the context of future studies. PMID- 26666699 TI - Viremia in North American Mammals and Birds After Experimental Infection with Chikungunya Viruses. AB - Chikungunya virus (CHIKV) is an arthropod-borne virus, which is known to cause severe disease only in humans. To investigate its potential zoonotic host range and evaluate reservoir competence among these hosts, experimental infections were performed on individuals from nine avian and 12 mammalian species representing both domestic and wild animals common to North America. Hamsters and inbred mice have previously been shown to develop viremia after inoculation with CHIKV and were used as positive controls for infection. Aside from big brown bats (Eptesicus fuscus), none of the mammals or birds developed detectable viremia or overt clinical disease. However, most mammals and a smaller proportion of birds developed neutralizing antibody responses to CHIKV. On the basis of these results, it seems unlikely that CHIKV poses a significant health threat to most domestic animals or wildlife and that the species examined do not likely contribute to natural transmission cycles. Additional studies should further evaluate bats and wild rodents as potential reservoir hosts for CHIKV transmission during human epidemics. PMID- 26666700 TI - Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia. AB - The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. PMID- 26666702 TI - A novel strategy for selective gene delivery by using the inhibitory effect of blue light on jetPRIME-mediated transfection. AB - Photodynamic control of gene delivery is a new technology with growing applications in gene therapy and basic cell research. Main approaches of light selective gene delivery rely on the light-dependent enhancement of transfection efficiency. Studies focused on light-stimulated inhibitory regulation of transfection have rarely been reported. Here, we tried to establish a novel procedure of light-dependent inhibition of transfection. Our experiments, conducted with several types of commercial transfection reagents, revealed that jetPRIME-mediated transfection was strongly inhibited by blue light. Although the uptake of reagent-DNA complex was drastically reduced, preliminary exposure of cells or reagent-DNA complex to blue light had no inhibitory effect on the transfection efficiency. The inhibitory effect was wavelength-dependent and mediated by reactive oxygen species. Partial exposure of a culture vessel to blue light resulted in selective gene delivery into cells grown on the unexposed area of the vessel. By using this approach, different types of plasmid DNA were delivered into different areas in the culture vessel. This novel approach to the inhibitory control of transfection provides practical options for research and therapeutics. Biotechnol. Bioeng. 2016;113: 1560-1567. (c) 2015 Wiley Periodicals, Inc. PMID- 26666701 TI - Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis. AB - Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD. PMID- 26666703 TI - Clinical features of functional somatic symptoms in children and referral patterns to child and adolescent mental health services. AB - AIM: Functional somatic symptoms (FSS) are common in paediatric patients who are referred to Child and Adolescent Mental Health Service (CAMHS), but little is known about current referral practices. The aim of this study was to systematically investigate clinical features of paediatric inpatients with FSS referred to CAMHS and to describe why paediatricians referred them. METHODS: The study population comprised 60 children with FSS admitted to a large Danish paediatric department during 2012. We compared medical record data on the clinical characteristics and paediatric management of 16 children who had been referred and 44 children who had not. RESULTS: Most paediatric records lacked information on psychosocial factors and symptoms. Referred children were significantly more multisymptomatic of FSS (p < 0.01) than the controls, had longer symptom duration, underwent more clinical investigations, had longer paediatric admissions of at least two weeks and received more treatment elements before referral. The most frequently stated referral reason was inadequate treatment response. CONCLUSION: Paediatric inpatients with more severe FSS were more likely to be referred to CAMHS, but referral reasons were generally vague and psychosocial information was frequently missing. Clinical guidelines are needed to improve and systematise mental health referrals for children with FSS. PMID- 26666704 TI - Dynamic and Static Water Molecules Complement the TN16 Conformational Heterogeneity inside the Tubulin Cavity. AB - TN16 is one of the most promising inhibitors of alpha, beta dimer of tubulin that occupies the cavity in the beta-subunit located at the dimeric interface, known as the colchicine binding site. The experimentally determined structure of the complex (Protein Data Bank entry 3HKD) presents the conformation and position of the ligand based on the "best fit", keeping the controversy of other significant binding modes open for further investigation. Computation has already revealed that TN16 experiences fluctuations within the binding pocket, but the insight from that previous report was limited by the shorter windows of sampling and by the approximations on the surrounding environment by implicit solvation. This article reports that in most of the cases straightforward MMGBSA calculations of binding energy revealed a gradual loss of stabilization that was inconsistent with the structural observations, and thus, it indicated the lack of consideration of stabilizing factors with appropriate weightage. Consideration of the structurally packed water molecules in the space between the ligand and receptor successfully eliminated such discrepancies between the structure and stability, serving as the "litmus test" of the importance of explicit consideration of such structurally packed water in the calculations. Such consideration has further evidenced a quasi-degenerate character of the different binding modes of TN16 that has rationalized the observed intrinsic fluctuations of TN16 within the pocket, which is likely to be the most critical insight into its entropy-dominated binding. Quantum mechanical calculations have revealed a relay of electron density from TN16 to the protein via a water molecule in a concerted manner. PMID- 26666705 TI - Predictive factors of response to mTOR inhibitors in neuroendocrine tumours. AB - Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs. PMID- 26666706 TI - Effect of handedness on brain activity patterns and effective connectivity network during the semantic task of Chinese characters. AB - Increasing efforts have been denoted to elucidating the effective connectivity (EC) among brain regions recruited by certain language task; however, it remains unclear the impact of handedness on the EC network underlying language processing. In particularly, this has not been investigated in Chinese language, which shows several differences from alphabetic language. This study thereby explored the functional activity patterns and the EC network during a Chinese semantic task based on functional MRI data of healthy left handers (LH) and right handers (RH). We found that RH presented a left lateralized activity pattern in cerebral cortex and a right lateralized pattern in cerebellum; while LH were less lateralized than RH in both cerebral and cerebellar areas. The conditional Granger causality method in deconvolved BOLD level further demonstrated more interhemispheric directional connections in LH than RH group, suggesting better bihemispheric coordination and increased interhemispheric communication in LH. Furthermore, we found significantly increased EC from right middle occipital gyrus to bilateral insula (INS) while decreased EC from left INS to left precentral gyrus in LH group comparing to RH group, implying that handedness may differentiate the causal relationship of information processing in integration of visual-spatial analysis and semantic word retrieval of Chinese characters. PMID- 26666707 TI - Ixekizumab: a new anti-IL-17A monoclonal antibody therapy for moderate-to severe plaque psoriasis. AB - INTRODUCTION: Psoriasis is a common, systemic, inflammatory disease with prominent skin and joint manifestations. Interleukin 17A (IL-17A) has been identified as a key effector cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab, a humanized monoclonal antibody that targets IL-17A, has been found in clinical trials to dramatically reduce signs and symptoms of moderate-to-severe plaque psoriasis. AREAS COVERED: The following areas are discussed: the basic structure and function of IL-17A, its role in the pathogenesis of psoriasis, the safety and efficacy of ixekizumab in clinical trials reported to date, and the possible impact of ixekizumab on the future therapeutic market for psoriasis. EXPERT OPINION: A large proportion of patients with psoriasis achieve clear or near clear skin during treatment with ixekizumab in a rapid and sustained manner. This supports the idea that IL-17A plays a central role in psoriasis immunopathogenesis. While ixekizumab has been shown to be safe in trials up to 60 weeks, long-term safety data are not yet available. Because its efficacy is higher than all previously approved drugs for psoriasis thus far, approval and use of ixekizumab may lead to a treatment paradigm change for psoriasis, where clear or near clear skin becomes an acceptable and achievable treatment goal. PMID- 26666708 TI - Intraoral pH and temperature during sleep with and without mouth breathing. AB - To measure and compare the intraoral pH and temperature of individuals during sleep with and without mouth breathing. Ten healthy participants [mean age = 25.8 (+/- 4.3)] wore a custom-made appliance fitted with a pH probe and thermocouple for two sets of 48 h. Continuous pH and temperature measurements were taken from the palatal aspect of the upper central incisors. To simulate mouth breathing during sleep, participants wore a nose clip for two nights of the four, with the first group (n = 5) wearing the nose clip during the first night and the rest (n = 5) wearing the nose clip during the second night of sleep to balance any potential bias from the wearing sequence. Both qualitative and quantitative analyses were conducted. The mean intraoral pH during daytime was 7.3 (+/- 0.4) and during sleep was 7.0 (+/- 0.5). The mean intraoral pH during sleep with mouth breathing was 6.6 (+/- 0.5), which was statistically significant compared with the normal sleep condition (P < 0.01). The intraoral pH decreased slowly over the hours of sleep in all participants. When sleeping with forced mouth breathing, intraoral pH showed a greater fall over a longer period of time. The mean intraoral temperature was 33.1 degrees C (+/- 5.2) during daytime and 33.3 degrees C (+/- 6.1) during sleep, with no statistical significance between sleep with and without mouth breathing (P > 0.05). The results suggest that mouth breathing during sleep is related to a decrease in intraoral pH compared with normal breathing during sleep, and this has been proposed as a causal factor for dental erosion and caries. PMID- 26666709 TI - Accumulation of 2,4-dinitroanisole in the earthworm Eisenia fetida from chemically spiked and aged natural soils. AB - An initiative within the US military is targeting the replacement of traditional munitions constituents with insensitive munitions to reduce the risk of accidental detonation. The bioavailability and bioaccumulative potential of the insensitive munitions compound 2,4-dinitroanisole (DNAN) to Eisenia fetida was assessed in soils with different geochemical characteristics. Prior to exposure, soils were chemically spiked with DNAN and aged for 1 wk or 29 wk. Transformation products 2- and 4-amino-nitroanisole (2A-4NAN and 4A-2NAN) occurred in aged soils and their porewater but never at concentrations higher than the residual DNAN. The sum of DNAN, 2A-4NAN, and 4A-2NAN (sumDNAN) in soil decreased with aging, likely by irreversible binding. Both clay and organic matter contents of the soil appeared to affect the bioavailability of DNAN. The sumDNAN body residues of earthworms approached apparent steady state after 1 d and remained relatively constant through to day 7. Higher concentrations of 2A-4NAN and 4A-2NAN measured in worm tissues relative to those in soil suggest reductive transformation of DNAN in the tissues. Mean bioaccumulation factors (ratio of tissue to soil concentrations) varied from 1.2 to 4.3, whereas mean bioconcentration factors (ratio of tissue to porewater concentrations) ranged from 1.4 to 3.2. Porewater seems to play a significant role in the accumulation of DNAN in earthworms, consistent with equilibrium partitioning theory. The concentration of DNAN in soil porewater could serve as an indicator of bioavailability as well as a predictor of the concentration of that compound in earthworms. Environ Toxicol Chem 2016;35:1835-1842. Publlished 2015 SETAC. This article is a US Government work, and as such, is in the public domain in the United States of America. PMID- 26666711 TI - Prescription Birth Control Access Among U.S. Women at Risk of Unintended Pregnancy. AB - BACKGROUND: Access to contraception is a vital component of preventing unintended pregnancies. This study was conducted to assess the prevalence of and factors associated with U.S. women's difficulty accessing prescription contraception (pill, patch, or ring). MATERIALS AND METHODS: We performed a nationally representative survey of adult women at risk of unintended pregnancy (aged 18-44, not pregnant or seeking pregnancy, sexually active, not sterilized) using a probability-based web panel. In November to December 2011, 2046 women completed the survey. Weighted proportions were calculated and logistic regression was used to identify covariates associated with difficulty obtaining or refilling prescription contraception. RESULTS: A total of 1385 (68%) women had ever tried to get a prescription for hormonal contraception. Among this population, 29% reported ever having problems obtaining a prescription or refills. In multivariable regression, uninsured (vs. privately insured) and Spanish-speaking (vs. English-speaking) women were significantly more likely to report difficulties; women with a high school degree and those with some college (vs. a college degree or higher) were significantly less likely to report difficulty. Difficulties included cost barriers or lack of insurance (14%), challenges obtaining an appointment or getting to a clinic (13%), the clinician requiring a clinic visit, exam, or Pap smear (13%), not having a regular doctor/clinic (10%), difficulty accessing a pharmacy (4%), and other reasons (4%). CONCLUSIONS: One third of adult U.S. women who have ever tried to obtain prescription contraception reported access barriers. While the Affordable Care Act may resolve some of these issues, these data indicate that additional factors may still need to be addressed. PMID- 26666710 TI - Effects of pyrrolidine dithiocarbamate on proliferation and nuclear factor-kappaB activity in autosomal dominant polycystic kidney disease cells. AB - BACKGROUND: Pyrrolidine dithiocarbamate (PDTC) reduces renal cyst growth in a rodent model of polycystic kidney disease (PKD) but the mechanism of action is not clear. Here, we investigated the hypothesis that PDTC reduces the proliferation of cystic epithelial cells in vitro in a nuclear factor (NF)-kappaB dependent manner. METHODS: Immortalized autosomal dominant PKD (ADPKD) cells that are heterozygous (WT9-7) and homozygous (WT-9-12) for a truncating Pkd1 mutation, and immortalized normal human tubular cells (HK-2), were exposed to NF-kappaB inducing agents with or without PDTC. Cell proliferation and apoptosis were assessed by bromodeoxyuridine assay and Annexin V flow cytometry, respectively. NF-kappaB activity was assessed by luciferase reporter assay and western blotting for nuclear p65, p50, and RelB subunits and cytoplasmic phosphorylated IkappaBalpha. RESULTS: Serum-induced proliferation was similar in all cell lines over 72 h. PDTC demonstrated anti-proliferative effects that were delayed in ADPKD cells compared to HK-2. Basal NF-kappaB-dependent luciferase reporter activity was lower in ADPKD cells compared to normal cells. Classical NF-kappaB stimulants, lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha, increased NF-kappaB luciferase activity in HK-2, whereas in PKD cell lines, NF kappaB activity was only induced by TNF-alpha. However, neither stimulant altered proliferation in any cell line. PDTC reduced TNF-alpha-stimulated NF-kappaB activity in HK-2 only. CONCLUSIONS: PDTC reduced proliferation in ADPKD cells but did not consistently alter NF-kappaB activation, suggesting that other signalling pathways are likely to be involved in its ability to attenuate renal cyst growth in vivo. PMID- 26666712 TI - Constructing Ionic Liquid-Filled Proton Transfer Channels within Nanocomposite Membrane by Using Functionalized Graphene Oxide. AB - Herein, nanocomposite membranes are fabricated based on functionalized graphene oxides (FGOs) and sulfonated poly(ether ether ketone) (SPEEK), followed by being impregnated with imidazole-type ionic liquid (IL). The functional groups (acidic group or basic group) on FGOs generate strong interfacial interactions with SPEEK chains and then adjust their motion and stacking. As a result, the nanocomposite membranes possess tunable interfacial domains as determined by its free volume characteristic, which provides regulated location for IL storage. The stored ILs act as hopping sites for water-free proton conduction along the FGO-constructed interfacial channels. The microstructure at SPEEK-FGO interface governs the IL uptake and distribution in nanocomposite membrane. Different from GO and vinyl imidazole functionalized GO (VGO), the presence of acidic (-SO3H) groups confers the p-styrenesulfonic acid functionalized GO (SGO) incorporated nanocomposite membrane loose interface and strong electrostatic attraction with imidazole-type IL, imparting an enhanced IL uptake and anhydrous proton conductivity. Nanocomposite membrane containing 7.5% SGO attains the maximum IL uptake of 73.7% and hence the anhydrous conductivity of 21.9 mS cm(-1) at 150 degrees C, more than 30 times that of SPEEK control membrane (0.69 mS cm(-1)). In addition, SGOs generate electrostatic attractions to the ILs confined within SGO-SPEEK interface, affording the nanocomposite membrane enhanced IL retention ability. PMID- 26666714 TI - [Mutations of epigenetic regulator genes and myeloid malignancies]. AB - Recent genome studies have identified recurrent somatic mutations in various myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndrome and myeloproliferative neoplasm. These mutations frequently occur in epigenetic regulator genes, and functions of the proteins encoded by these genes in hematopoietic cells have been extensively analyzed, as reported recently. It is noteworthy that several epigenetic regulator genes, such as DNMT3A, TET2 and ASXL1, have also been identified in pre-leukemic stem cells. As targeting pre leukemic stem cells would be a promising therapeutic approach, further investigations of epigenetic abnormalities in hematopoietic cells are anticipated to lead to the development of novel epigenetic therapies. In this review, we discuss recent genetic and functional data regarding epigenetic regulator genes and the future landscape of this new research field. PMID- 26666716 TI - [Microscopic study and microanalysis of platelets in vivo]. AB - Under physiological and pathological conditions, complex cellular interplays take place in living animals. However, the conventional microscope using two dimensional analysis is not sufficient for analyzing cell dynamics and functions in vivo. Thus, we improved the in vivo imaging technique based on multi-photon microscopy, and we then identified single platelet behaviors in the developing thrombus. We utilized XYZT high-speed imaging, which visualized platelet fate in vivo. This novel technique is anticipated to provide new insights into physiological and pathological conditions involving platelets. PMID- 26666715 TI - [Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma]. AB - PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL). EXPERIMENTAL DESIGN: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients. RESULTS: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL. CONCLUSIONS: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO. PMID- 26666717 TI - [The clinical significance of decrease in CD138 positive cell ratio in multiple myeloma]. AB - CD138 has been considered to be strongly expressed in multiple myeloma cells. However, CD138+ cells were decreased in some patients during the course of treatment. To clarify the clinical significance of this finding, we evaluated the correlations of CD138 levels with laboratory data employing flow cytometry. We found that CD138+ cells were decreased in 12 patients during treatment and were retained in the remaining 105 patients throughout their clinical courses. For nine (75%) patients in the CD138+ cells reduced group, median survival time was 25 months after the reduction in CD138+ cells was detected, and all nine died of myeloma. Furthermore, extramedullary lesions and specific cytogenetic abnormalities [del(17p), t(4;14), amplification of c-MYC] were observed in some patients when the number of CD138+ cells started to decrease. Interestingly, 2 of 3 patients who survived until the end of observation period showed re-increase in their CD138+ levels. Taking these observations together, it is unclear whether reduction of the number of CD138+ cells is associated with a poor prognosis and resistance to drugs. However, if treatment does not produce a reincrease in CD138+ levels, long term survival might be difficult to achieve. PMID- 26666718 TI - [Successful treatment with rituximab of a patient with coincident acquired hemophilia A and thrombotic thrombocytopenic purpura]. AB - A 66-year-old man was admitted for oral hemorrhage, purpura, and APTT prolongation. Factor VIII (FVIII) activity was decreased, due to the presence of FVIII inhibitor. He was diagnosed with acquired hemophilia A (AHA) and treated with prednisolone. Eight months later, the FVIII inhibitor titer again increased. Upon readmission, thrombocytopenia and autoimmune hemolytic anemia were found. We suspected Evans syndrome accompanied by AHA, and we treated the patient with IVIG. However, his platelet count did not increase. Speech disturbance and delirium were observed from the 12th day of hospitalization. He was subsequently diagnosed with thrombotic thrombocytopenic purpura (TTP) because ADAMTS13 inhibitor was detected, causing a decrease in ADAMTS13 activity. We initiated plasma exchange (PE) and steroid-pulse therapy. After PE for 3 days, laboratory test results and psychiatric symptoms showed dramatic improvement. However, after a 2-day period without PE, the patient's platelet count decreased markedly. Therefore, we administered rituximab to eliminate these inhibitors. His platelet count recovered rapidly, and we were able to gradually wean the patient from PE. After two additional administrations of rituximab, neither inhibitor was detected. To date, the patient has remained in complete remission for approximately 3 years. PMID- 26666719 TI - [Pure red cell aplasia and hypogammaglobulinemia after administration of Dioscorea rhizome and Poria cocos]. AB - A 56-year-old woman was referred to our department for detailed examination of anemia. She was diagnosed with pure red cell aplasia (PRCA) associated with severe reticulocytopenia based on blood testing and severe erythroblastopenia based on bone marrow aspiration. Blood tests revealed severe hypogammaglobulinemia, but monoclonal protein was not detected in either serum or urine by immunoelectrophoresis. Plasma cells were not increased in bone marrow aspirates or the biopsy specimen. Neither osteolytic lesions nor plasmacytoma was detected by computed tomography. We thus ruled out multiple myeloma. She had been treated with various Chinese herbal medicines prescribed at the referring hospital. We suspected PRCA induced by one of the Chinese herbal medicines and completely discontinued all of these herbal preparations. Hematologic testing revealed that the reticulocyte count and hemoglobin concentration began to recover on day 7 and the hemoglobin concentration and IgG levels had reached reference ranges on day 73 after discontinuation of the Chinese herbal medicines. We suspected Sanyaku (Dioscorea rhizome) or Bukuryou (Poria cocos) to have induced PRCA and hypogammaglobulinemia in this patient. To the best of our knowledge, this is the first report of PRCA and hypogammaglobulinemia induced by a Chinese herbal medicine. Clinicians must consider the possibility of drug induced PRCA and hypogammaglobulinemia in patients taking Chinese herbal preparations. PMID- 26666720 TI - [RS3PE syndrome associated with senile Epstein-Barr virus-positive diffuse large B cell lymphoma of a patient with colon cancer]. AB - A 75-year-old woman consulted her doctor in January 2014 because of pain in the dorsum of the hands, elbows, shoulders, and knees, bilaterally, and was diagnosed as having remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Although the joint pain improved with low-dose prednisolone administration, she was referred to our department in April of 2014 because she had become aware of swelling of the right cervical lymph node. Biopsy of the lymph node demonstrated that she had Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly, and colonoscopy revealed early colon cancer. Also, both the lymphoma and colon cancer stained positive for vascular endothelial growth factor (VEGF). Complete remission was achieved after two courses of R-CHOP, and RS3PE syndrome did not relapse. This case suggested the involvement of VEGF produced by EBV-positive DLBCL in the pathogenesis of RS3PE syndrome. PMID- 26666721 TI - [Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura]. AB - We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 * 104/MUl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 * 104/MUl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 * 104/MUl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock. PMID- 26666722 TI - [Autoimmune hemolytic anemia with normal serum lactate dehydrogenase level]. AB - We herein report two cases of AIHA (autoimmune hemolytic anemia), a 25-year-old woman and a 77-year-old man, who presented with normal serum LDH values. Though in these two cases, low hemoglobin and haptoglobin, high total bilirubin and positive direct Coombs' test results led to the diagnosis of AIHA, both patients had normal LDH levels (218 and 187 IU/l). Both cases were successfully treated with prednisone. In the diagnosis of AIHA, elevated LDH is usually used as a marker of hemolysis. However, medical records of 24 AIHA patients collected in our institute from January 2001 to August 2012 revealed LDH levels to have been normal in 25% of these cases. This report indicates the importance of obtaining complete information about the blood testing of patients and taking these data into account when considering the diagnosis of AIHA. PMID- 26666723 TI - [Autoimmune hemolytic anemia in a patient with TAFRO syndrome]. AB - TAFRO syndrome is a systemic inflammatory disorder characterized by low platelet counts, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. Patients with TAFRO syndrome occasionally have courses complicated by immunological diseases. Herein, we describe a case of TAFRO syndrome associated with autoimmune hemolytic anemia (AIHA). The patient was admitted because of menorrhagia. She had thrombocytopenia, pleural effusion and ascites, hepatomegaly, and multiple lymphadenopathies. Her symptoms worsened, especially fever, pleural effusion and ascites, and she developed AIHA. Steroid pulse therapy followed by 45 mg of prednisolone (PSL) improved not only the symptoms of TAFRO syndrome but also those of AIHA. There have been no reports, to our knowledge, of AIHA associated with TAFRO syndrome, and detailed studies on this syndrome are needed. PMID- 26666724 TI - [Diffuse large B-cell lymphoma occurring in a Waldenstrom macroglobulinemia patient with central nervous system infiltration]. AB - The rare central nervous system (CNS) infiltration of Waldenstrom macroglobulinemia (WM) is known as Bing-Neel syndrome (BNS). Furthermore, the transformation of WM into diffuse large B-cell lymphoma (DLBCL) is also unusual. Herein, we report a 69-year-old male with DLBCL transformed from BNS. In November 2008, the patient visited a prior hospital because of anemia and was diagnosed with WM. After receiving chemotherapy (R-CHOP), his serum immunoglobulin M (IgM) level decreased and then remained at approximately 2000 mg/dl for 3 years. In November 2011, he complained of visual impairment and photophobia in his left eye. Magnetic resonance imaging showed enlargement of the left optic nerve and cerebrospinal fluid examination indicated CNS infiltration of WM cells. Consequently, he was diagnosed with BNS. He thus received CNS targeted chemotherapy (R-MPV) and achieved a partial response. In May 2014, IgM was elevated and swelling of systemic lymph nodes was detected. Inguinal lymph node biopsy yielded a pathological diagnosis of DLBCL and the clonality of tumor cells between WM and DLBCL was confirmed by the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). PMID- 26666729 TI - Furan quantification in bread crust: development of a simple and sensitive method using headspace-trap GC-MS. AB - To study reactivity in bread crust during the baking process in the pan, we followed furan mainly resulting from Maillard and caramelisation reactions in cereal products. Furan quantification is commonly performed with automatic HS static GC-MS. However, we showed that the automatic HS-trap GC-MS method can improve the sensitivity of the furan quantification. Indeed, this method allowed the LOD to be decreased from 0.3 ng g(-1) with HS-static mode to 0.03 ng g(-1) with HS-trap mode under these conditions. After validation of this method for furan quantification in bread crust, a difference between the crust extracted from the bottom and from the sides of the bread was evident. The quantity of furan in the bottom crust was five times lower than in the side crust, revealing less reactivity on the bottom than on the sides of the bread during the baking process in the pan. Differences in water content may explain these variations in reactivity. PMID- 26666730 TI - Editorial. PMID- 26666731 TI - The hepatoprotective effect of the combination use of Fructus Schisandrae with statin--A preclinical evaluation. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Schisandrae is traditionally used as a liver-toning Chinese herb. Recent studies suggested Fructus Schisandrae could prevent high-fat diet-induced hepatic steatosis as well as improving anti oxidative status within the liver, which is a proposed mechanism against statin induced liver toxicity. AIM: The aim of the present study was to determine if the combination use of Atorvastatin (AS) and Fructus Schisandrae aqueous extract (FSE) could (a) exert potent therapeutic effects not only on high-fat diet induced hyperlipidemia, but also on hepatomegaly (enlarge of liver size) and hepatic steatosis (fatty liver); and (b) reduce side effects caused by intake of statin alone including increased incidence of elevated liver enzymes and liver toxicity in Sprague Dawley rats. MATERIALS AND METHODS: We studied 5 groups of Sprague Dawley rats that were given the following treatment for 8 weeks: (i) Normal-chow diet; (ii) High-fat diet (contains 21% fat and 0.15% cholesterol); (iii) High-fat diet (contains 21% fat and 0.15% cholesterol)+0.3% Atorvastatin; (iv) High-fat diet (contains 21% fat and 0.15% cholesterol)+0.45% FSE; (v) High fat diet (contains 21% fat and 0.15% cholesterol)+0.3% Atorvastatin+0.45% FSE. After 8 weeks of treatment, body weight, adipose tissue and liver mass were measured, and liver and plasma lipid levels were determined to evaluate to effect of FSE with or without AS treatment on diet-induced obesity, hyperlipidemia and hepatic steatosis. Liver enzyme activities, anti-oxidative status and membrane permeability transition were also assessed to determine if FSE could reduce the side effects induced by AS. RESULTS: From the results, FSE treatment alone resulted in significant inhibitory effect on diet-induced increase in: (a) body weight; (b) fat pad mass (epididymal, perirenal and inguinal fat); (c) liver weight; (d) total liver lipid; (e) liver triglyceride and cholesterol levels; and (f) plasma lipid levels, suggesting FSE has a potential preventive beneficial effect on weight control and lipid metabolism in Sprague Dawley rats with diet induced obesity. However, FSE supplementation exerted no further beneficial effect on diet-induced metabolic syndrome when it is combined with AS treatment, compared with rats given AS-treatment alone. At the dose of 0.45%, dietary FSE supplementation resulted in: (a) reduced liver enzymes (ALT and AST) levels; (b) reduced macrophage infiltration (CD68); (c) improved liver glutathione levels (anti-oxidative status); (d) reduced liver reactive oxidative species; (e) a trend to reduce calcium-induced membrane permeability transition within the liver. Most importantly, these improvements induced by FSE treatment were not only observed in the livers of rats given high-fat-diet, but also in high-fat-fed rats with atorvastatin-induced hepatotoxicity. CONCLUSIONS: Taken together, these data suggested FSE has a potential beneficial effect on weight control and lipid metabolism in Sprague Dawley rats with diet-induced obesity, and the combination use of FSE with AS could significantly prevent liver toxicity and anti-oxidative status induced by AS alone. PMID- 26666732 TI - A traditional herbal medication, Maekmoondong-tang, for cough: A systematic review and meta-analysis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Maekmoondong-tang (MMDT) is a traditional herbal medication widely used to improve cough in Korea, Japan, and China. It is composed of six herbs (Ophiopogonis Tuber, Pinelliae Tuber, Glycyrrhizae Radix, Zizyphi Fructus, Ginseng Radix, and Oryzae Semen). AIM OF THE STUDY: This study is aimed to systematically review the relevant randomised controlled trials (RCTs) to determine the effectiveness and safety of MMDT for cough. MATERIALS AND METHODS: Electronic and hand-searching of 7 databases (Cochrane Library, MEDLINE, EMBASE, OASIS, RISS, CNKI and CiNii) was systematically conducted up to February 2015 for RCTs testing MMDT in patients with cough. The primary outcome was cough symptom improvement using cough diary, visual analog scale, or response rate. Risk of bias of the included trials was evaluated with the Cochrane risk of bias assessment tool. The dichotomous data were pooled to obtain a risk ratio (RR) of cough persisting after treatment, with 95% confidence intervals (CI). RESULTS: Nine RCTs involving 2453 participants were included. The methodological quality was largely poor for a majority of the studies. MMDT reduced the severity of cough by 74% compared with the conventional antitussive medications in various conditions (n=1145; RR of cough persisting after treatment=0.26; 95% CI, 0.19 0.34, I(2)=0%). The addition of MMDT to conventional medication in patients with postinfectious cough significantly alleviated symptoms up to day 5 but the effect was not maintained one week afterwards. For other diseases/conditions including chronic obstructive pulmonary disease, lung cancer surgery, and asthma, the evidence is inconsistent for MMDT/mMMDT for cough. Adverse events appear to be rare but the reporting was poor. CONCLUSIONS: The current evidence from our systematic review and meta-analysis on MMDT for cough is inconclusive and we propose that rigorously designed, placebo-controlled trials of MMDT should be conducted to establish its place in management of cough. PMID- 26666734 TI - Patient-specific fracture risk assessment of vertebrae: A multiscale approach coupling X-ray physics and continuum micromechanics. AB - While in clinical settings, bone mineral density measured by computed tomography (CT) remains the key indicator for bone fracture risk, there is an ongoing quest for more engineering mechanics-based approaches for safety analyses of the skeleton. This calls for determination of suitable material properties from respective CT data, where the traditional approach consists of regression analyses between attenuation-related grey values and mechanical properties. We here present a physics-oriented approach, considering that elasticity and strength of bone tissue originate from the material microstructure and the mechanical properties of its elementary components. Firstly, we reconstruct the linear relation between the clinically accessible grey values making up a CT, and the X-ray attenuation coefficients quantifying the intensity losses from which the image is actually reconstructed. Therefore, we combine X-ray attenuation averaging at different length scales and over different tissues, with recently identified 'universal' composition characteristics of the latter. This gives access to both the normally non-disclosed X-ray energy employed in the CT-device and to in vivo patient-specific and location-specific bone composition variables, such as voxel-specific mass density, as well as collagen and mineral contents. The latter feed an experimentally validated multiscale elastoplastic model based on the hierarchical organization of bone. Corresponding elasticity maps across the organ enter a finite element simulation of a typical load case, and the resulting stress states are increased in a proportional fashion, so as to check the safety against ultimate material failure. In the young patient investigated, even normal physiological loading is probable to already imply plastic events associated with the hydrated mineral crystals in the bone ultrastructure, while the safety factor against failure is still as high as five. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26666736 TI - Ultrasound measures of supraspinatus tendon thickness and acromiohumeral distance in rotator cuff tendinopathy are reliable. AB - PURPOSE: Rotator cuff (RC) tendinopathy has been widely ascribed to impingement of the supraspinatus tendon (SsT) in the subacromial space, measured as the acromiohumeral distance (AHD). Ultrasound (US) is suitable for measuring AHD and SsT thickness, but few reliability studies have been carried out in symptomatic populations, and interrater reliability is unconfirmed. This study aimed to examine the intrarater and interrater reliability of US measurements of AHD and SsT thickness in asymptomatic control subjects and patients with RC tendinopathy. METHODS: Seventy participants were recruited and grouped as healthy controls (n = 25) and RC tendinopathy (n = 45). Repeated US measurements of AHD and SsT thickness were obtained by one rater in both groups and by two raters in the RC tendinopathy group. RESULTS: Intrarater and interrater reliability coefficients were excellent for both measurements (intraclass correlation > 0.92), but the intrarater reliability was superior. The minimal detectable change values in the symptomatic group were 0.7 mm for AHD and 0.6 mm for SsT thickness for a single experienced examiner; the values rose to 1.2 mm and 1.3 mm, respectively, for the pair of examiners. CONCLUSIONS: The results support the reliability of US for the measurement of AHD and SsT thickness in patients with symptomatic RC tendinopathy and provide minimal detectable change values for use in future research studies. PMID- 26666737 TI - The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis. AB - BACKGROUND: Elevated neutrophil count is associated with poor prognosis and increased mortality in many conditions. Neutrophil to lymphocyte ratio (NLR) has emerged as a marker of inflammation in neoplastic and cardiovascular disorders. Herein, we investigated utility of this simple tool in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study consisted of 136 RA and 140 AS patients, along with 117 healthy control subjects. RA and AS activities were determined with Disease Activity Score (DAS) and Bath Ankylosing Spondylitis Disease Activity indices (BASDAI), respectively. The association between NLR and disease activity was analyzed. RESULTS: Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and neutrophil counts were significantly higher in RA and AS patients compared to healthy controls. Similarly, NLR was higher compared to control subjects, both in RA (2.53 +/- 1.4 vs. 2.16 +/- 1.0, P = 0.019) and AS (2.43 +/- 1.4 vs. 2.16 +/- 1.0, P = 0.077). NLR correlated well with ESR and CRP, both in RA and AS. Moreover, NLR increased across worsening DAS28 activity groups (2.1 +/- 1.0 in patients with remission, 2.5 +/- 1.0 in low-moderate, 3.8 +/- 2.5 in high disease activity). However, no association was found between NLR and BASDAI. CONCLUSION: NLR is a cheap and readily available marker for the assessment of disease activity in RA. PMID- 26666733 TI - Animal Models of Maternal Immune Activation in Depression Research. AB - BACKGROUND: Depression and schizophrenia are debilitating mental illnesses with significant socio-economic impact. The high degree of comorbidity between the two disorders, and shared symptoms and risk factors, suggest partly common pathogenic mechanisms. Supported by human and animal studies, maternal immune activation (MIA) has been intimately associated with the development of schizophrenia. However, the link between MIA and depression has remained less clear, in part due to the lack of appropriate animal models. OBJECTIVE: Here we aim to summarize findings obtained from studies using MIA animal models and discuss their relevance for preclinical depression research. METHODS: Results on molecular, cellular and behavioral phenotypes in MIA animal models were collected by literature search (PubMed) and evaluated for their significance for depression. RESULTS: Several reports on offspring depression-related behavioral alterations indicate an involvement of MIA in the development of depression later in life. Depression-related behavioral phenotypes were frequently paralleled by neurogenic and neurotrophic deficits and modulated by several genetic and environmental factors. CONCLUSION: Literature evidence analyzed in this review supports a relevance of MIA as animal model for a specific early life adversity, which may prime an individual for the development of distinct psychopathologies later life. MIA animal models may present a unique tool for the identification of additional exogenous and endogenous factors, which are required for the manifestation of a specific neuropsychiatric disorder, such as depression, later in life. Hereby, novel insights into the molecular mechanisms involved in the pathophysiology of depression may be obtained, supporting the identification of alternative therapeutic strategies. PMID- 26666738 TI - Intraoperative infusion of branched-chain amino acids in patients undergoing gastrointestinal tumor surgery. AB - BACKGROUND: The purpose of this study is to investigate the effects of intraoperative infusion of branched-chain amino acids (BCAA) in patients undergoing gastrointestinal tumor surgery. METHODS: Sixty-one patients with gastrointestinal tumors undergoing gastrointestinal surgery were enrolled and randomly assigned to receive an intraoperative infusion of 3-compound BCAA solution (N = 20), amino acids (AA) solution (N = 21), or normal saline (NS) (N = 20). Nasopharyngeal temperature, blood glucose (BG), plasma insulin, and blood free fatty acids (FFA) concentrations were measured at 30 min before and 10 min after induction (T 0,T 1), 30 min and 2 h after skin incision (T 2,T 3), and 1 h after tracheal extubation (T 4). Intensity of shivering and pain was accessed at 1 h after extubation. RESULTS: The temperature in the BCAA and AA group was significantly higher than that in the NS group at T 4 (P = 0.014 and 0.033). The incidence of shivering in the BCAA and AA group was significantly lower than in the NS group (P = 0.027 and 0.012). BG increased in AA group at T 3 and T 4 (P = 0.001 and 0.045). The plasma insulin concentration increased in the BCAA and AA group from T 1 to T 3. The plasma FFA concentrations in the BCAA group were lower than in the AA and NS group from T 2 to T 4. CONCLUSIONS: Intraoperative BCAA and AA infusion alleviated postoperative hypothermia and shivering. BCAA infusion also inhibited fat mobilization, without adversely affecting blood glucose. TRIAL REGISTRATION: ChiCTR-TRC-14004668. PMID- 26666740 TI - Evaluation of autochthonous micrococcus strains as starter cultures for the production of Kedong sufu. AB - AIMS: The technological properties of 22 micrococcus strains from traditional fermented Kedong sufu were evaluated in order to develop autochthonous starter cultures. METHODS AND RESULTS: The proteolytic, autolytic and lipolytic activity, salt tolerance, production and degradation of the biogenic amines of six Micrococcus luteus, nine Kocuria kristinae and seven Kocuria rosea were evaluated. The results indicated that these micrococcus strains exhibited a certain technological diversity, and the results also indicated the best properties to be used in mixed starter cultures. Based on the above findings, two sets of autochthonous starters were formulated. Considering the physicochemical properties and sensory characteristics of sufu, the maturation period of sufu was shortened by 30 days. The profiles of free amino acids and peptides partly revealed the mechanism of sensory quality and shorter ripening time of sufu manufactured using autochthonous mixed starters. Compared to back-slopping fermentation, sufu manufactured with selected autochthonous starter cultures exhibited lower levels of total biogenic amines. CONCLUSIONS: The selected strains could be used as starter to avoid the accumulation of high concentrations of biogenic amines while also maintaining typical sensory characteristics and preserving the autochthonous strains of the traditional Kedong sufu. The maturation times of Kedong sufu were shortened by 30 days with application of the autochthonous starter. SIGNIFICANCE AND IMPACT OF THE STUDY: Autochthonous mixed starters can reduce the generation of biogenic amines, speed up the sufu maturation process and preserve typical sensory quality. Furthermore, the rotation of two sets of mixed starter cultures can effectively resist phage attack during the production of sufu. PMID- 26666739 TI - Development and characterization of a eukaryotic expression system for human type II procollagen. AB - BACKGROUND: Triple helical collagens are the most abundant structural protein in vertebrates and are widely used as biomaterials for a variety of applications including drug delivery and cellular and tissue engineering. In these applications, the mechanics of this hierarchically structured protein play a key role, as does its chemical composition. To facilitate investigation into how gene mutations of collagen lead to disease as well as the rational development of tunable mechanical and chemical properties of this full-length protein, production of recombinant expressed protein is required. RESULTS: Here, we present a human type II procollagen expression system that produces full-length procollagen utilizing a previously characterized human fibrosarcoma cell line for production. The system exploits a non-covalently linked fluorescence readout for gene expression to facilitate screening of cell lines. Biochemical and biophysical characterization of the secreted, purified protein are used to demonstrate the proper formation and function of the protein. Assays to demonstrate fidelity include proteolytic digestion, mass spectrometric sequence and posttranslational composition analysis, circular dichroism spectroscopy, single-molecule stretching with optical tweezers, atomic-force microscopy imaging of fibril assembly, and transmission electron microscopy imaging of self assembled fibrils. CONCLUSIONS: Using a mammalian expression system, we produced full-length recombinant human type II procollagen. The integrity of the collagen preparation was verified by various structural and degradation assays. This system provides a platform from which to explore new directions in collagen manipulation. PMID- 26666741 TI - Carcinoid Heart Disease without Severe Tricuspid Valve Involvement. AB - Carcinoid syndrome causes a rare form of acquired valvular heart disease which typically occurs in the setting of liver metastases. In carcinoid-induced valvular heart disease, the tricuspid valve is almost universally affected; left sided valve disease occurs infrequently in affected patients. Herein, we report 2 cases of carcinoid-induced valvular heart disease; one case had no evidence of tricuspid valve involvement despite severe involvement of all other valves, while the other case was without severe tricuspid valve involvement. PMID- 26666742 TI - Can Exercise Positively Influence the Intervertebral Disc? AB - To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research. PMID- 26666744 TI - Effect of Training Leading to Repetition Failure on Muscular Strength: A Systematic Review and Meta-Analysis. AB - BACKGROUND: It remains unclear whether repetitions leading to failure (failure training) or not leading to failure (non-failure training) lead to superior muscular strength gains during resistance exercise. Failure training may provide the stimulus needed to enhance muscular strength development. However, it is argued that non-failure training leads to similar increases in muscular strength without the need for high levels of discomfort and physical effort, which are associated with failure training. OBJECTIVE: We conducted a systematic review and meta-analysis to examine the effect of failure versus non-failure training on muscular strength. METHODS: Five electronic databases were searched using terms related to failure and non-failure training. Studies were deemed eligible for inclusion if they met the following criteria: (1) randomised and non-randomised studies; (2) resistance training intervention where repetitions were performed to failure; (3) a non-failure comparison group; (4) resistance training interventions with a total of >=3 exercise sessions; and (5) muscular strength assessment pre- and post-training. Random-effects meta-analyses were performed to pool the results of the included studies and generate a weighted mean effect size (ES). RESULTS: Eight studies were included in the meta-analysis (combined studies). Training volume was controlled in four studies (volume controlled), while the remaining four studies did not control for training volume (volume uncontrolled). Non-failure training resulted in a 0.6-1.3% greater strength increase than failure training. A small pooled effect favouring non-failure training was found (ES = 0.34; p = 0.02). Significant small pooled effects on muscular strength were also found for non-failure versus failure training with compound exercises (ES = 0.37-0.38; p = 0.03) and trained participants (ES = 0.37; p = 0.049). A slightly larger pooled effect favouring non-failure training was observed when volume-uncontrolled studies were included (ES = 0.41; p = 0.047). No significant effect was found for the volume-controlled studies, although there was a trend favouring non-failure training. The methodological quality of the included studies in the review was found to be moderate. Exercise compliance was high for the studies where this was reported (n = 5), although limited information on adverse events was provided. CONCLUSION: Overall, the results suggest that despite statistically significant effects on muscular strength being found for non-failure compared with failure training, the small percentage of improvement shown for non-failure training is unlikely to be meaningful. Therefore, it appears that similar increases in muscular strength can be achieved with failure and non-failure training. Furthermore, it seems unnecessary to perform failure training to maximise muscular strength; however, if incorporated into a programme, training to failure should be performed sparingly to limit the risks of injuries and overtraining. PMID- 26666743 TI - Intramuscular Anabolic Signaling and Endocrine Response Following Resistance Exercise: Implications for Muscle Hypertrophy. AB - Maintaining skeletal muscle mass and function is critical for disease prevention, mobility and quality of life, and whole-body metabolism. Resistance exercise is known to be a major regulator for promoting muscle protein synthesis and muscle mass accretion. Manipulation of exercise intensity, volume, and rest elicit specific muscular adaptations that can maximize the magnitude of muscle growth. The stimulus of muscle contraction that occurs during differing intensities of resistance exercise results in varying biochemical responses regulating the rate of protein synthesis, known as mechanotransduction. At the cellular level, skeletal muscle adaptation appears to be the result of the cumulative effects of transient changes in gene expression following acute bouts of exercise. Thus, maximizing the resistance exercise-induced anabolic response produces the greatest potential for hypertrophic adaptation with training. The mechanisms involved in converting mechanical signals into the molecular events that control muscle growth are not completely understood; however, skeletal muscle protein synthesis appears to be regulated by the multi-protein phosphorylation cascade, mTORC1 (mammalian/mechanistic target of rapamycin complex 1). The purpose of this review is to examine the physiological response to resistance exercise, with particular emphasis on the endocrine response and intramuscular anabolic signaling through mTORC1. It appears that resistance exercise protocols that maximize muscle fiber recruitment, time-under-tension, and metabolic stress will contribute to maximizing intramuscular anabolic signaling; however, the resistance exercise parameters for maximizing the anabolic response remain unclear. PMID- 26666746 TI - Potential therapeutic targets in plasma cell disorders: A flow cytometry study. AB - The discovery of new targets for tailored therapy is a major improvement in oncology, and tools for the rapid and reliable detection of these targets are essential. Clinical trials demonstrated the benefit of recently developed antibodies against antigens on malignant B-cells. The aim of this study was to assess patients with plasma cell (PC) disorders for expression of antigens on malignant PCs that have exhibited promise in targeted cancer therapy. We retrospectively analyzed the expression of CD20, CD22, CD27, CD30, CD38, CD52, CD81, CD138, and SLAMF7 on PCs by flow cytometry in 103 patients with PC disorders. Furthermore, we studied cytogenetic data to correlate immunophenotyping and genetic parameters. The expression frequency of CD22, CD30, and CD52 was similar to other studies (12-35%, 0-19%, and 0-8%, respectively). Unexpectedly, we observed a high CD20 expression frequency in 37% of all AL amyloidosis cases. The presence of t(11;14) correlated positively with CD20 expression on PCs in AL-amyloidosis (p = 0.018). Furthermore, the expression level of SLAMF7 was decreased in advanced PC disorders (p = 0.025) and a diminished expression of SLAMF7 is associated with low expression of CD27 and CD81 on malignant PCs in newly diagnosed multiple myeloma. This study provides a contribution to targeted therapy options in PC disorders. Particularly, the results put an emphasis on CD20 as therapeutic target in AL-amyloidosis. Regarding the therapeutic options of the SLAMF7 antibody elotuzumab, these data advise that analysis of SLAMF7 expression before application of elotuzumab might help to estimate the efficacy of elotuzumab in clinical trials. (c) 2015 International Clinical Cytometry Society. PMID- 26666745 TI - Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease. AB - Sickle cell disease is a class of hemoglobinopathy in humans, which is the most common inherited disease in the world. Although complications of sickle cell disease start from polymerization of red blood cells during its deoxygenating phase, the oxidative stress resulting from the biological processes associated with this disease (ischaemic and hypoxic injuries, hemolysis and inflammation) has been shown to contribute to its pathophysiology. It is widely known that chronic exercise reduces oxidative stress in healthy people, mainly via improvement of antioxidant enzyme efficiency. In addition, recent studies in other diseases, as well as in sickle cell trait carriers and in a mouse model of sickle cell disease, have shown that regular physical activity could decrease oxidative stress. The purpose of this review is to summarize the role of oxidative stress in sickle cell disease and the effects of acute and chronic exercise on the pro-oxidant/antioxidant balance in sickle cell trait and sickle cell disease. PMID- 26666748 TI - Effect of 24 Cytochrome P450 2D6 Variants Found in the Chinese Population on Atomoxetine Metabolism in vitro. AB - OBJECTIVE: The aim of this article was to assess the catalytic activities of 24 cytochrome P450 2D6 (CYP2D6) variants found in the Chinese population toward atomoxetine in vitro as well as CYP2D6.1. METHODS: In this study, the co expression enzyme of human recombinant CYPOR, CYPb5, and CYP2D6.1 or other CYP2D6 variants with the baculovirus-mediated insect cells (Sf21) was used to study the catalytic activities of 24 CYP2D6 variants toward atomoxetine metabolism. The metabolite of atomoxetine (4-hydroxyatomoxetine) was detected by ultra-high performance liquid chromatography-mass spectrometry method. RESULTS: The intrinsic clearance (Vmax/Km) values of most variants were significantly altered when compared with CYP2D6.1. CYP2D6.94, CYP2D6.D336N, CYP2D6.R440C exhibited marked increased values 172, 126, 121% respectively. CYP2D6.89 and CYP2D6.98 exhibited similar catalytic activity as the wild type, whereas 17 variants exhibited significantly decreased values (from 5 to 87%) due to increase Km and/or decrease Vmax values. However, CYP2D6.92 and CYP2D6.96 showed no or few activity because of producing nothing. CONCLUSIONS: Our results suggest that most of these newly found variants exhibit significantly changed catalytic activities compared with the wild type. And these findings provide valuable information for the growth and development of personalized medicine in China. PMID- 26666747 TI - In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-beta load in aged APPPS1-21 mice. AB - INTRODUCTION: Radioligand imaging is a powerful in vivo method to assess the molecular basis of Alzheimer's Disease. We therefore aimed to visualize the pathological deposition of fibrillar amyloid-beta and neuronal dysfunction in aged double transgenic mice. METHODS: Using non-invasive positron emission tomography (PET) we assessed brain glucose utilization with [(18)F]FDG and fibrillar amyloidosis with [(11)C]PiB and [(18)F]AV45 in 12 month old APPPS1-21 (n = 10) mice and their age-matched wild-type controls (n = 15). PET scans were analyzed with statistical parametric mapping (SPM) to detect significant differences in tracer uptake between genotypes. After imaging, mice were sacrificed and ex vivo measures of amyloid-beta burden with immunohistochemistry as well as glucose utilization with [(14)C]-2DG autoradiography were obtained as gold standards. RESULTS: Voxel-wise SPM analysis revealed significantly decreased [(18)F]FDG uptake in aged APPPS1-21 mice in comparison to WT with the thalamus (96.96 %, maxT = 3.35) and striatum (61.21 %, maxT = 3.29) demonstrating the most widespread reductions at the threshold of p < 0.01. [(11)C]PiB binding was significantly increased in APPPS1-21 mice, most notably in the hippocampus (87.84 %, maxT = 7.15) and cortex (69.08 %, maxT = 7.95), as detected by SPM voxel-wise analysis at the threshold of p < 0.01. Using the same threshold [(18)F]AV45 uptake was comparably lower with less significant differences. Compared to their respective ex vivo equivalents [(18)F]FDG demonstrated significant positive correlation to [(14)C]2-DG autoradiography (r = 0.67, p <0.0001) while [(11)C]PiB and [(18)F]AV45 binding did not correlate to ex vivo immunohistochemistry for amyloid-beta (r = 0.25, p = 0.07 and r = 0.17, p = 0.26 respectively). Lastly no correlation was observed between regions of high amyloid burden and those with decreased glucose utilization (r = 0.001, p = 0.99). CONCLUSIONS: Our findings support that fibrillar amyloid-beta deposition and reduced glucose utilization can be visualized and quantified with in vivo MUPET imaging in aged APPPS1-21 mice. Therefore, the combined use of [(18)F]FDG and amyloid MUPET imaging can shed light on the underlying relationship between fibrillar amyloid-beta pathology and neuronal dysfunction. PMID- 26666749 TI - Dihydropyridines' metabolites-induced early apoptosis after myocardial infarction in rats; new outlook on preclinical study with M-2 and M-3. AB - Our previous studies established cardio-protective effects of furnidipine and its active metabolites called M-2 and M-3. The aim of current research was to compare the effects of single oral pretreatment with 20 mg kg(-1) of M-2 and M-3 on mortality, different forms of arrhythmias, blood pressures parameters and ST segment changes during occlusion (for 90 min) and reperfusion in the model of myocardial infarction in rats evoked by left anterior descending coronary artery occlusion. Additionally, the development of programmed cell death and biochemical parameters in blood serum were studied at 4th day after infarction. Furnidipines' metabolites effectively reduced mortality index while did not markedly influence on blood pressures parameters, arrhythmias, ST-segment changes as well as biochemical parameters. Intriguingly, programmed cell death study (TUNEL) showed distinct increase in the amount of apoptotic nuclei in post-infarcted myocardium, granulation tissue and what is more in arteriolar walls after M-2 and M-3 application. Moreover, M-2 turned out to be more powerful in stimulation of apoptosis in granulation tissue surrounding infarcted area whereas M-3 presented balanced profile in this matter. Taking into account that programmed cell death plays positive role in post-infarcted heart healing, M-2 presents itself as more attractive agent for oral pretreatment in early stages of ischemia by non-stable individuals due to its more specific action in stimulation repairing processes in granulation tissue as well as in arteriolar walls. While M-2 and M-3 are common metabolites present in degradation pathways of many widely used dihydropyridines in clinic, this key fact put the new outlook on understanding additional mechanism and effects of not only furnidipines' metabolites but also other dihydropyridines. PMID- 26666751 TI - IRAK4 inhibition to shut down TLR signaling in autoimmunity and MyD88-dependent lymphomas. PMID- 26666750 TI - Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway. AB - Protein N-terminal acetylation is an abundant post-translational modification in eukaryotes implicated in various fundamental cellular and biochemical processes. This modification is catalysed by evolutionarily conserved N-terminal acetyltransferases (NATs) whose deregulation has been linked to cancer development and thus, are emerging as useful diagnostic and therapeutic targets. Naa40 is a highly selective NAT that acetylates the amino-termini of histones H4 and H2A and acts as a sensor of cell growth in yeast. In the present study, we examine the role of Naa40 in cancer cell survival. We demonstrate that depletion of Naa40 in HCT116 and HT-29 colorectal cancer cells decreases cell survival by enhancing apoptosis, whereas Naa40 reduction in non-cancerous mouse embryonic fibroblasts has no effect on cell viability. Specifically, Naa40 knockdown in colon cancer cells activates the mitochondrial caspase-9-mediated apoptotic cascade. Consistent with this, we show that caspase-9 activation is required for the induced apoptosis because treatment of cells with an irreversible caspase-9 inhibitor impedes apoptosis when Naa40 is depleted. Furthermore, the effect of Naa40-depletion on cell-death is mediated through a p53-independent mechanism since p53-null HCT116 cells still undergo apoptosis upon reduction of the acetyltransferase. Altogether, these findings reveal an anti-apoptotic role for Naa40 and exhibit its potential as a therapeutic target in colorectal cancers. PMID- 26666752 TI - Colon contradictions: NF-kappaB signaling in intestinal tumorigenesis. PMID- 26666753 TI - An autoimmune "attack" on melanocytes triggers psoriasis and cellular hyperplasia. PMID- 26666754 TI - Hypoxia factors suffocate leukemic stem cell initiation. PMID- 26666756 TI - Determining phylogenetic networks from inter-taxa distances. AB - We consider the problem of determining the topological structure of a phylogenetic network given only information about the path-length distances between taxa. In particular, one of the main results of the paper shows that binary tree-child networks are essentially determined by such information. PMID- 26666755 TI - The significance of pre-therapeutic F-18-FDG PET-CT in lymphoma-associated hemophagocytic lymphohistiocytosis when pathological evidence is unavailable. AB - PURPOSE: The significance of positron emission tomography/computed tomography (PET-CT) in identifying patients with lymphoma-associated hemophagocytic lymphohistiocytosis (LAHLH) when pathological evidence is unavailable remains uncertain. METHODS: In this retrospective study, 44 HLH patients who underwent PET-CT before clinical treatment were enrolled, and 18 of them were highly suspected as LAHLH by PET-CT. We compared the PET-CT parameters between confirmed LAHLH and non-LAHLH patients. The efficacy of initial therapies for highly suspected LAHLH patients was analyzed as well. RESULTS: We found that the SUVSp, SUVBM, SUVLN, SUVmax, SUVLN/Li, and SUVmax/Li in LAHLH group were significantly higher than those in non-LAHLH group (p = 0.003, p = 0.034, p = 0.003, p < 0.001, p = 0.039, and p = 0.035, respectively). HLH patients with an SUVmax value >5.5, an SUVLN value >3.3, and an SUVSp value >4.8 were more likely to be LAHLH (p < 0.001, p = 0.003, and p = 0.003, respectively). And the incidence of multiple lymphadenopathy with increased FDG uptake or the incidence of multiple bone lesions in LAHLH patients was significantly higher than those in non-LAHLH group (92.9 vs. 35.7 %, p = 0.004; 42.9 vs. 0 %, p = 0.016, respectively). Furthermore, by comparing the efficacy of initial therapies for highly suspected LAHLH patients (n = 18), we indicated that the CR rate was significantly higher in lymphoma-chemotherapy group than in immunosuppressive therapy group (90 and 25 %, respectively; p = 0.013). OS analysis revealed that highly suspected LAHLH patients treated with lymphoma-chemotherapy had better prognosis (264 days) than those treated with immunosuppressive therapy (15 days) (p < 0.0001). CONCLUSIONS: When pathological evidence is absent, PET-CT may play an important role in identifying HLH patients underlying lymphoma. Once highly suspected as LAHLH by PET-CT, lymphoma-chemotherapies that directly treat the underling lymphoma may have a relatively favorable effect and better clinical outcomes than immunosuppressive therapy. PMID- 26666757 TI - FlexFlux: combining metabolic flux and regulatory network analyses. AB - BACKGROUND: Expression of cell phenotypes highly depends on metabolism that supplies matter and energy. To achieve proper utilisation of the different metabolic pathways, metabolism is tightly regulated by a complex regulatory network composed of diverse biological entities (genes, transcripts, proteins, signalling molecules...). The integrated analysis of both regulatory and metabolic networks appears very insightful but is not straightforward because of the distinct characteristics of both networks. The classical method used for metabolic flux analysis is Flux Balance Analysis (FBA), which is constraint-based and relies on the assumption of steady-state metabolite concentrations throughout the network. Regarding regulatory networks, a broad spectrum of methods are dedicated to their analysis although logical modelling remains the major method to take charge of large-scale networks. RESULTS: We present FlexFlux, an application implementing a new way to combine the analysis of both metabolic and regulatory networks, based on simulations that do not require kinetic parameters and can be applied to genome-scale networks. FlexFlux is based on seeking regulatory network steady-states by performing synchronous updates of multi-state qualitative initial values. FlexFlux is then able to use the calculated steady state values as constraints for metabolic flux analyses using FBA. As input, FlexFlux uses the standards Systems Biology Markup Language (SBML) and SBML Qualitative Models Package ("qual") extension (SBML-qual) file formats and provides a set of FBA based functions. CONCLUSIONS: FlexFlux is an open-source java software with executables and full documentation available online at http://lipm-bioinfo.toulouse.inra.fr/flexflux/. It can be defined as a research tool that enables a better understanding of both regulatory and metabolic networks based on steady-state simulations. FlexFlux integrates well in the flux analysis ecosystem thanks to the support of standard file formats and can thus be used as a complementary tool to existing software featuring other types of analyses. PMID- 26666758 TI - "Gunslinger's gait": a new cause of unilaterally reduced arm swing. AB - OBJECTIVE: To postulate a new possible cause of a unilaterally reduced arm swing in addition to the known medical conditions such as shoulder pathology, Erb's palsy, stroke, and Parkinson's disease. METHODS: Analysis of YouTube videos depicting the gait of highly ranked Russian officials. RESULTS: We found a similar walking pattern in President Vladimir Putin, Prime Minister Dmitry Medvedev and three other highly ranked Russian officials, all presenting with a consistently reduced right arm swing in the absence of other overt neurological abnormalities. CONCLUSIONS: We propose that this new gait pattern, which we term "gunslinger's gait," may result from a behavioural adaptation, possibly triggered by KGB or other forms of weapons training where trainees are taught to keep their right hand close to the chest while walking, allowing them to quickly draw a gun when faced with a foe. This should be included in the differential diagnosis of a unilaterally reduced arm swing. PMID- 26666759 TI - Spatial and seasonal variations in the composition of dissolved organic matter in a tropical catchment: the Lower Kinabatangan River, Sabah, Malaysia. AB - Dissolved organic matter (DOM) was characterised in water samples sampled in the Lower Kinabatangan River Catchment, Sabah, Malaysia between October 2009 and May 2010. This study aims at: (i) distinguishing between the quality of DOM in waters draining palm oil plantations (OP), secondary forests (SF) and coastal swamps (CS) and, (ii) identifying the seasonal variability of DOM quantity and quality. Surface waters were sampled during fieldwork campaigns that spanned the wet and dry seasons. DOM was characterised optically by using the fluorescence Excitation Emission Matrix (EEM), the absorption coefficient at 340 nm and the spectral slope coefficient (S). Parallel Factor Analysis (PARAFAC) was undertaken to assess the DOM composition from EEM spectra and five terrestrial derived components were identified: (C1, C2, C3, C4 and C5). Components C1 and C4 contributed the most to DOM fluorescence in all study areas during both the wet and dry seasons. The results suggest that component C4 could be a significant (and common) PARAFAC signal found in similar catchments. Peak M (C2 and C3) was dominant in all samples collected during wet and dry seasons, which could be anthropogenic in origin given the active land use change in the study area. In conclusion, there were significant seasonal and spatial variations in DOM which demonstrated the effects of land use cover and precipitation amounts in the Kinabatangan catchment. PMID- 26666760 TI - Siddharta Mukherjee's three laws of medicine. PMID- 26666761 TI - Effect of Compound Zhebei Granule () combined with chemotherapy on surface markers of leukemia stem cell in patients with acute myeloid leukemia. AB - OBJECTIVE: To observe the effects of Compound Zhebei Granule (, CZBG) combined with chemotherapy on surface markers of leukemia stem cell (LSC) in the bone marrow of patients with acute myeloid leukemia (AML). METHODS: Seventy-eight patients with AML received bone marrow aspiration and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were tested using flow cytometry method. A total of 24 refractory or relapsed AML patients were enrolled and treated with one cycle of standard chemotherapy combined with CZBG. Bone marrow samples were obtained before and after treatment, and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were examined by flflow cytometry. RESULTS: Compared with refractory or relapsed AML patients, patients achieved remission had a significant lower percentage of CD34(+) CD123(+) cells(P<0.01) and CD33(+) CD123(+) cells (P<0.01), indicating that controlling the LSC percentage may be important for patients with AML to achieve sustainable remission. Compared with those before treatment, the expression levels of CD34(+) CD123(+) were significantly decreased after CZBG combined with chemotherapy treatment (P<0.01). The percentages of CD34(+) CD123(+) cells and CD33(+) CD123(+) in patients achieving complete remission after CZBG combined with chemotherapy treatment were both significantly lower than those in patients with nonremission (P<0.01). CONCLUSION: CZBG combining chemotherapy could reduce the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) LSC, which might improve the clinical efficacy of refractory or relapsed AML. PMID- 26666762 TI - Wenxia Changfu Formula () induces apoptosis of lung adenocarcinoma in a transplanted tumor model of drug-resistance nude mice. AB - OBJECTIVE: To explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo. METHODS: Thirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase activated DNase (CAD), respectively. RESULTS: Compared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05). CONCLUSION: WCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis. PMID- 26666763 TI - Screening of the BRCA1 gene in Brazilian patients with breast and/or ovarian cancer via high-resolution melting reaction analysis. AB - The aim of this study was to evaluate the profile of BRCA1 mutations among cancer affected Brazilian women from the Midwest region of Minas Gerais state with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. In this Brazilian region, the first Center for Hereditary Cancer Control began operation in 2011, and 90% of patients receive assistance from the public health service. Eighteen patients at high risk for HBOC were subjected to molecular analysis. Primers were designed for 22 coding exons of the gene; DNA was extracted; and real-time PCR followed by high-resolution melting reaction was performed. The amplicons were sequenced to confirm the identified profiles. Only exon 11 was directly sequenced due its length. Multiplex ligation-dependent probe amplification (MLPA) was performed for those patients in whom no pathogenic mutations were found. Among the 14 alterations identified in this study, the c.5263_5264insC pathogenic mutation was present in two patients (11.1%). Four alterations showed no clinical relevance; one exhibited inconclusive clinical relevance according to the examined databases; and eight alterations presented a divergent classification between the databases. No deletions or duplications were found using the MLPA technique. The HRM methodology was highly sensitive in identifying variants in the BRCA1 gene and can dramatically reduce the amount of sequencing required to identify germline mutations in BRCA genes, enabling cheaper tests and increasing their availability to Brazilian women assisted by the public health service. PMID- 26666764 TI - Associations between allergic conditions and pediatric brain tumors in Neurofibromatosis type 1. AB - Individuals with Neurofibromatosis type 1 (NF1) are at increased risk for pediatric brain tumors (PBTs), especially optic gliomas; however, factors influencing their development are largely unknown. Extensive research suggests that allergic conditions protect against brain tumors, particularly gliomas in individuals without NF1. In this large cross-sectional study, we employed two different data sources to evaluate evidence for the hypothesis that allergic conditions (allergies, asthma, and eczema) may protect against PBT development in individuals with NF1. We used self- and parent/legal guardian reported questionnaire data from participants in the NF1 Patient Registry Initiative (NPRI, n = 1660) born from 1933 to 2014 to ascertain allergic condition and PBT diagnosis histories. Medical records (MRs) of 629 NF1 patients at a large medical center born from 1930 to 2012 were also reviewed for PBT and allergic condition diagnoses to evaluate additional evidence for our hypothesis. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between allergic condition diagnoses and PBTs. Both data sources provided limited to no support for a protective effect of allergies or eczema on PBT development. Non-significant inverse associations between asthma and PBTs were observed (NPRI: OR = 0.80, 95% CI 0.55-1.17; MR: OR = 0.71, 95% CI 0.40 1.28) with stronger associations for optic gliomas specifically. Additionally, a significant inverse association was observed in an NPRI subgroup analysis where the reported asthma diagnosis age was younger than the reported PBT diagnosis age (OR = 0.57; 95% CI 0.36-0.89). Our study supports the hypothesis that asthma protects against PBT development in NF1. PMID- 26666765 TI - Mismatch repair deficiency concordance between primary colorectal cancer and corresponding metastasis. AB - Universal screening for mismatch repair deficiency (dMMR) in cancer is increasingly being implemented to detect Lynch syndrome and aid in treatment decisions. The mismatch repair (MMR) immunohistochemistry (IHC) concordance rate between primary colorectal cancer (CRC) and metastasis is unknown. At times, only metastatic tumor is available for screening (lymph node, liver, lung etc.) rather than the primary tumor. Therefore, it is important to confirm that tissue from metastases can be used for screening for dMMR. We tested dMMR primary and metastatic tumor to assess concordance between the two. We identified dMMR CRC resected at Ohio State University from 1999 to 2013 and stained a corresponding metastasis for all four MMR proteins (MLH1, MSH2, MSH6, PMS2) with IHC. A total of 50 primary CRC with dMMR and available regional lymph nodes (LN; 26 cases) or other metastatic tissue (24 cases) were identified. Thirteen cases were explained by MLH1 hypermethylation and 10 cases had Lynch syndrome. Two cases had somatic MMR mutations and the etiology for dMMR was unknown in 25 cases. All cases showed concordance in IHC staining between the primary tumor and corresponding metastatic tissue. In 36 cases, metastatic LN/other site was resected at the same time as the primary tumor. In 14 cases, time lapsed [median 16.5 months; quartile (Q)1 8.0; Q3 25; range 3-69] from the primary resection until metastatic resection. Metastatic tissue can be used to screen for Lynch syndrome and dMMR. PMID- 26666766 TI - High prevalence of cardiovascular comorbidities in patients with rheumatoid arthritis from a population-based cross-sectional study of a Japanese health insurance database. AB - OBJECTIVE: To reveal any association between rheumatoid arthritis (RA) and cardiovascular comorbidities using a Japanese health insurance database. METHOD: This population-based cross-sectional study was conducted using health insurance data provided by the Japan Medical Data Center Co., Ltd. We identified 2762 RA subjects having RA diagnostic codes (ICD10 codes; M05, M060, M062-63, M068-069) with at least two physician visits more than two months apart between June 2011 and May 2012 (RA group, n = 2762). We selected age- (+/-5 years), sex-, and study period-matched non-RA subjects (non-RA group, n = 27,620). We compared the prevalence of cardiovascular and related comorbidities (ischemic heart diseases [IHD], cerebral infarction, hypertension [HT], dyslipidemia [DL], and diabetes mellitus [DM]) between these groups and investigated the association between RA and cardiovascular comorbidities using a conditional logistic regression analysis. RESULTS: The prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group. Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 2.0 [1.5-2.5] and 3.1 [2.2-4.2] respectively, after adjusting for HT, DL, and DM. CONCLUSIONS: This study revealed for the first time in the Japanese population that RA was significantly associated with cardiovascular comorbidities. PMID- 26666767 TI - [About the "lemon cure" and the limits of S3 guidelines]. PMID- 26666768 TI - [Psychotherapy and pharmacotherapy for harmful tobacco use and tobacco dependency]. AB - Tobacco consumption is one of the major preventable health risk factors. In Germany approximately 110,000 people prematurely die from tobacco-related diseases and approximately 50% of regular smokers are considered to be tobacco dependent. Nevertheless, motivation to quit smoking is low and the long-term abstinence rates after attempts to stop smoking without professional support are far below 10%. As part of the S3 treatment guidelines 78 recommendations for motivation and early interventions for smokers unwilling to quit as well as psychotherapeutic and pharmacological support for smokers willing to quit were formulated after an systematic search of the current literature. More than 50 professional associations adopted the recommendations and background information in a complex certification process. In this article the scientific evidence base regarding the psychotherapeutic and pharmacological treatment options as well as recommendations and further information about indications and treatment implementation are presented. By following these guidelines for treatment of heavy smokers who are willing to quit combined with individual and group therapies on the basis of behavioral treatment strategies and pharmacological support, long-term success rates of almost 30% can be achieved. PMID- 26666769 TI - Patterns and management of distant failure in locally advanced rectal cancer: a cohort study. AB - PURPOSE: To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed. METHODS: Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines +/- oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan. RESULTS: The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Kohne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p < 0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p < 0.001). CONCLUSIONS: Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate. PMID- 26666771 TI - Encouraging Health Insurance for the Informal Sector: A Cluster Randomized Experiment in Vietnam. AB - Subsidized voluntary enrollment in government-run health insurance schemes is often proposed as a way of increasing coverage among informal sector workers and their families. We report the results of a cluster randomized experiment, in which 3000 households in 20 communes in Vietnam were randomly assigned at baseline to a control group or one of three treatments: an information leaflet about Vietnam's government-run scheme and the benefits of health insurance, a voucher entitling eligible household members to 25% off their annual premium, and both. At baseline, the four groups had similar enrollment rates (4%) and were balanced on plausible enrollment determinants. The interventions all had small and insignificant effects (around 1 percentage point or ppt). Among those reporting sickness in the 12 months prior to the baseline survey the subsidy-only intervention raised enrollment by 3.5 ppts (p = 0.08) while the combined intervention raised enrollment by 4.5 ppts (p = 0.02); however, the differences in the effect sizes between the sick and non-sick were just shy of being significant. Our results suggest that information campaigns and subsidies may have limited effects on voluntary health insurance enrollment in Vietnam and that such interventions might exacerbate adverse selection. Copyright (c) The World Bank Health Economics (c) 2015 John Wiley & Sons, Ltd. PMID- 26666772 TI - Incentives for Starting Small Companies Focused on Rare and Neglected Diseases. AB - Starting biotech or pharmaceutical companies is traditionally thought to be based around a scientist, their technology platform or a clinical candidate spun out from another company. Between us we have taken a different approach and formed two small early stage companies after initially leveraging the perspective of a parent with a child with a life-threatening rare disease. Phoenix Nest ( http://www.phoenixnestbiotech.com/ ) was co-founded to work on treatments for Sanfilippo syndrome a devastating neurodegenerative lysosomal storage disorder. In the space of just over 3 years we have built up collaborations with leading scientists in academia and industry and been awarded multiple NIH small business grants. The second company, Collaborations Pharmaceuticals Inc. ( http://www.collaborationspharma.com/ ) was founded to address some of the other 7000 or so rare diseases as well as neglected infectious diseases. The Rare Pediatric Disease Priority Review Voucher is likely the most important incentive for companies working on rare diseases with very small populations. This may also be partially responsible for the recent acquisitions of rare disease companies with late stage candidates. Lessons learned in the process of starting our companies are that rare disease parents or patients can readily partner with a scientist and fund research through NIH grants rather than venture capital or angel investors initially. This process may be slow so patience and perseverance is key. We would encourage other pharmaceutical scientists to meet rare disease parents, patients or advocates and work with them to further the science on their diseases and create a source of future drugs. PMID- 26666774 TI - A pilot randomized trial of nebulized amphotericin in patients with allergic bronchopulmonary aspergillosis. AB - BACKGROUND AND AIM: Nebulized amphotericin B (NAB) has been used in the management of acute stage and exacerbations of allergic bronchopulmonary aspergillosis (ABPA). Whether NAB can prevent exacerbations of ABPA is not known. Herein, we evaluate the efficacy and safety of NAB in subjects with ABPA complicating asthma. METHODS: Consecutive subjects of ABPA with recurrent exacerbations were randomized to receive either NAB plus nebulized budesonide (NEB) or NEB alone. The primary outcome was the time-to-first exacerbation of ABPA. The secondary outcomes were the number of subjects with ABPA exacerbations, ACQ7 scores, lung function, IgE levels, and adverse effects of treatment. RESULTS: Twenty-one subjects (14 men; mean age, 32.3 years) were randomized to either the NAB (n = 12) or the NEB (n = 9) arm. The baseline characteristics were similar in the two groups. The time-to-first exacerbation was similar in the two groups. At one year, the numbers of patients experiencing exacerbation was significantly lower in the NAB arm (1/12 [8.3%] vs. 6/9 [66.7%]; p = 0.016). The other secondary end points were not different between the two groups. There were no major adverse events leading to discontinuation of any of the study drugs. Three patients experienced bronchospasm after first dose of NAB; however, the subsequent doses were well tolerated. CONCLUSIONS: NAB seems to be beneficial in decreasing the frequency of exacerbations in patients with ABPA complicating asthma. Larger trials are required to confirm our study results. PMID- 26666773 TI - Multi-functional Liposomes Enhancing Target and Antibacterial Immunity for Antimicrobial and Anti-Biofilm Against Methicillin-Resistant Staphylococcus aureus. AB - PURPOSE: The aim of this study was to prepare wheat germ agglutinin (WGA) modified liposomes encapsulating clarithromycin and to evaluate their in vitro and in vivo efficacy against Methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Physicochemical parameters, minimum inhibitory concentrations, in vitro killing kinetic, cellular uptake, biofilm formation inhibition and pre-formed biofilm destruction, biodistribution, in vivo antibacterial efficacy against MRSA, and phagocytosis into macrophages for liposomes loading clarithromycin were determined. RESULTS: The minimum inhibitory concentration and the time-kill curve for WGA-modified liposomal clarithromycin were better than those of free and nonmodified liposomal clarithromycin. Flow cytometry analysis displayed that liposomes could deliver more Coumarin 6, a fluorescent probe, into bacteria because of the conjugation of WGA. Besides, WGA-modified liposomal clarithromycin inhibited formation of S. aureus (ATCC 29213) and MRSA biofiom, and prompted the biofilm disassembly at lower concentrations below MIC. Effective accumulation of liposomes was displayed in the enterocoelia of the mice because of WGA. The number of MRSA colony-forming units in the kidney and spleen in mice treated with WGA-modified liposomal clarithromycin was significantly lower than that treated with free and nonmodified clarithromycin (p < 0.05). Intracellular localization of MRSA occurred in a significantly higher proportion of macrophage exposed to WGA-modified liposomes compared to those exposed to nonmodified liposomes. CONCLUSIONS: Liposome modified by WGA is a promising formulation for bacteria targeted delivery and immunity defensive system through macrophage improving uptake of bacteria, biodistribution, in vitro and in vivo antibacterial efficacy against MRSA. PMID- 26666775 TI - Benign paroxysmal positional vertigo commonly occurs following repair of superior canal dehiscence. AB - OBJECTIVES/HYPOTHESIS: Repair of superior canal dehiscence (SCD) often results in the resolution of preoperative auditory and vestibular symptoms; however, many patients experience dizziness in the postoperative period. Postoperative dizziness may be the result of new-onset benign paroxysmal positional vertigo (BPPV). This study aims to investigate the prevalence of BPPV before and following SCD repair. STUDY DESIGN: Retrospective chart review at a tertiary care center. METHODS: Electronic medical records were reviewed for patients with a diagnosis of SCD syndrome (SCDS) between January 2002 and May 2015. Collected information included demographic data, incidence of BPPV diagnosed by Dix Hallpike maneuver before and following surgery, operative technique, repair material, and the duration of time to BPPV onset. RESULTS: A total of 180 patients with a diagnosis of SCDS were identified: 84 patients underwent surgery (operated subjects) and 96 were observed (nonoperated, control group). In operated subjects, 20 of 84 (23.8%) developed BPPV following SCD repair versus 6.2% of nonoperated (P < 0.005). Benign paroxysmal positional vertigo lateralized to the operated side in all but one subject whose laterality was unknown (P < 0.0001). There were no associations of BPPV with surgical approach (P = 0.50) or repair material (P = 0.33). The majority of subjects (58%) were diagnosed with BPPV within 3 months of surgery. CONCLUSION: New-onset BPPV occurs commonly after SCD repair and may be the result of mobilized otoliths from inner ear pressure changes. Although the exact etiology of post-SCD repair BPPV remains unknown, postoperative dizziness is important to discuss with patients during preoperative counseling. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2092-2097, 2016. PMID- 26666776 TI - Stabilization of a two-coordinate, acyclic diaminosilylene (ADASi): completion of the series of isolable diaminotetrylenes, :E(NR(2))(2) (E = group 14 element). AB - An extremely bulky boryl-amide ligand, [N(SiMe3){B(DAB)}](-) (TBoN; DAB = (DipNCH)2, Dip = C6H3Pr(i)2-2,6), has been utilised in the preparation of the first isolable, two-coordinate acyclic diaminosilylene (ADASi), viz. :Si(TBoN)2. This is shown to have a frontier orbital energy separation, and presumed level of reactivity, intermediate between those of the two classes of previously reported isolable two-coordinate, acyclic silylenes. PMID- 26666777 TI - Structural and spectroscopic characterisation of a heme peroxidase from sorghum. AB - A cationic class III peroxidase from Sorghum bicolor was purified to homogeneity. The enzyme contains a high-spin heme, as evidenced by UV-visible spectroscopy and EPR. Steady state oxidation of guaiacol was demonstrated and the enzyme was shown to have higher activity in the presence of calcium ions. A Fe(III)/Fe(II) reduction potential of -266 mV vs NHE was determined. Stopped-flow experiments with H2O2 showed formation of a typical peroxidase Compound I species, which converts to Compound II in the presence of calcium. A crystal structure of the enzyme is reported, the first for a sorghum peroxidase. The structure reveals an active site that is analogous to those for other class I heme peroxidase, and a substrate binding site (assigned as arising from binding of indole-3-acetic acid) at the gamma-heme edge. Metal binding sites are observed in the structure on the distal (assigned as a Na(+) ion) and proximal (assigned as a Ca(2+)) sides of the heme, which is consistent with the Ca(2+)-dependence of the steady state and pre steady state kinetics. It is probably the case that the structural integrity (and, thus, the catalytic activity) of the sorghum enzyme is dependent on metal ion incorporation at these positions. PMID- 26666778 TI - Promising bifunctional chelators for copper 64-PET imaging: practical (64)Cu radiolabeling and high in vitro and in vivo complex stability. AB - Positron emission tomography (PET) using copper-64 is a sensitive and non invasive imaging technique for diagnosis and staging of cancer. A bifunctional chelator that can present rapid radiolabeling kinetics and high complex stability with (64)Cu is a critical component for targeted PET imaging. Bifunctional chelates 3p-C-NE3TA, 3p-C-NOTA, and 3p-C-DE4TA were evaluated for complexation kinetics and stability with (64)Cu in vitro and in vivo. Hexadentate 3p-C-NOTA and heptadentate 3p-C-NE3TA possess a smaller TACN-based macrocyclic backbone, while nonadentate 3p-C-DE4TA is constructed on a larger CYCLEN-based ring. The frequently explored chelates of (64)Cu, octadentate C-DOTA and hexadentate C-NOTA were also comparatively evaluated. Radiolabeling kinetics of bifunctional chelators with (64)Cu was assessed under mild conditions. All bifunctional chelates instantly bound to (64)Cu in excellent radiolabeling efficiency at room temperature. C-DOTA was less efficient in binding (64)Cu than all other chelates. All (64)Cu-radiolabeled bifunctional chelates remained stable in human serum without any loss of (64)Cu for 2 days. When challenged by an excess amount of EDTA, (64)Cu complexes of C-NOTA, 3p-C-NE3TA and 3p-C-NOTA were shown to be more stable than (64)Cu-C-DOTA and (64)Cu-3p-C-DE4TA. (64)Cu complexes of the new chelates 3p-C-NE3TA and 3p-C-NOTA displayed comparable in vitro and in vivo complex stability to (64)Cu-C-NOTA. In vivo biodistribution result indicates that the (64)Cu-radiolabeled complexes of 3p-C-NOTA and 3p-C-NE3TA possess excellent in vivo complex stability, while (64)Cu-3p-C-DE4TA was dissociated as evidenced by high renal and liver retention in mice. The results of in vitro and in vivo studies suggest that the bifunctional chelates 3p-C-NE3TA and 3p-C-NOTA offer excellent chelation chemistry with (64)Cu for potential PET imaging applications. PMID- 26666779 TI - A new sesquiterpenoid from Polyalthia petelotii. AB - A new sesquiterpenoid (-)-ethyl dihydrophaseate (1) was isolated from the stems and leaves of Polyalthia petelotii, together with two clerodane diterpenoids, 16alpha-hydroxycleroda-3,13(14)Z-dien-15,16-olide (2), 15-hydroxy-cis-ent-cleroda 3,13(E)-diene (3), a eudesmane sesquiterpenoid, eudesm-4(15)-ene-7alpha,11-diol (4), an aromatic aldehyde, vanillin (5), a bisisoquinolines alkaloid, spinosine (6) and an aporphine alkaloid, (-)-oliveroline-beta-N-oxide (7). Their structures were established by extensive spectroscopic analysis, including 2D-NMR techniques. Compounds 3, 4 and 6 were isolated from the genus Polyalthia for the first time and the others obtained originally from P. petelotii. The isolates were assessed for their cytotoxicity against five human tumour lines (HL-60, SMMC 7721, A-549, MCF-7 and SW-480), and the result showed that only 2 displayed weak inhibitory activity. PMID- 26666780 TI - Correction to Multiconfiguration Pair-Density Functional Theory: A Fully Translated Gradient Approximation and Its Performance for Transition Metal Dimers and the Spectroscopy of Re2Cl8(2-). PMID- 26666781 TI - The Moral Agency of Physician Organizations: Meeting Obligations to Advocate for Patients and the Public. AB - The close of the American College of Physician's (ACP) centennial year is an opportune time to reflect on the organization's important role in professional development and advocating for sound health policy. Organized medicine provides a professional home where members can participate in scholarly activities and access guidance that will help them to be better doctors. Professional organizations also serve patients by improving physicians' knowledge and skill, being a public repository of health-related information, and advocating for improvement of public health. High-functioning medical professional organizations, such as ACP, also function intentionally as moral agents through well-designed efforts to advocate for patients and the public. PMID- 26666782 TI - Preexposure Prophylaxis for HIV Prevention: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. AB - The U.S. Public Health Service recently issued guidelines about the daily use of medication as preexposure prophylaxis (PrEP) to prevent HIV infection. The guidelines, based on randomized trials showing substantial reduction in HIV transmission among those receiving a daily combination of tenofovir and emtricitabine, suggest physicians offer PrEP to patients at high risk, including nonmonogamous men who have sex with men, serodiscordant couples (in both male male and male-female relationships), heterosexual men and women in other risk groups (such as sex workers or those with recent sexually transmitted infection), and injection drug users. Here, 2 prominent HIV experts debate the use of PrEP in a 45-year-old man whose husband has HIV infection with an undetectable viral load on treatment. They discuss the patient's risk for HIV transmission from his husband and from other partners, the magnitude of the risk reduction he would gain with PrEP, and nonpharmacologic alternatives to reduce his likelihood of contracting HIV infection. PMID- 26666783 TI - Celebrating the ACP Centennial: From the Annals Archive-HIV Research and Therapies. PMID- 26666784 TI - The Smile. PMID- 26666785 TI - Applying Strategies From Pediatrics to the Treatment of Hospitalized Adults. PMID- 26666787 TI - Gastroesophageal Reflux Disease. PMID- 26666786 TI - Applying Strategies From Pediatrics to the Treatment of Hospitalized Adults. In response. PMID- 26666788 TI - Gastroesophageal Reflux Disease. In response. PMID- 26666789 TI - Sexual Orientation Identity Disparities in Awareness and Initiation of the Human Papillomavirus Vaccine. PMID- 26666790 TI - Sexual Orientation Identity Disparities in Awareness and Initiation of the Human Papillomavirus Vaccine. In response. PMID- 26666791 TI - Lesbian, Gay, Bisexual, and Transgender Health Disparities. PMID- 26666792 TI - Lesbian, Gay, Bisexual, and Transgender Health Disparities. PMID- 26666793 TI - Lesbian, Gay, Bisexual, and Transgender Health Disparities. In response. PMID- 26666794 TI - Borrelia miyamotoi. PMID- 26666795 TI - Borrelia miyamotoi. In response. PMID- 26666796 TI - Correction: Unusal Infection Related to an Implantable Cardioverter-Defibrillator in a Dog Breeder. PMID- 26666797 TI - Correction: A Nutritional Formula Enriched With Arginine, Zinc, and Antioxidants for the Healing of Pressure Uclers. PMID- 26666799 TI - Web Exclusives. The Consult Guys - Excluding the Diagnosis of Pulmonary Embolism: Is There a Magic Ball? PMID- 26666800 TI - Review: Combination umeclidinium/vilanterol improved health status more than umeclidinium in COPD. PMID- 26666801 TI - Review: Digoxin does not affect all-cause mortality but reduces hospital admissions. PMID- 26666802 TI - Risk for septic arthritis was increased in adults with incident diagnosis of gout. PMID- 26666803 TI - Use of olmesartan for >= 1 year was associated with hospitalization for intestinal malabsorption. PMID- 26666804 TI - Review: Corticosteroids reduce mechanical ventilation and ARDS in inpatients with community-acquired pneumonia. PMID- 26666805 TI - Annual mammography in women 40 to 48 y of age reduced breast cancer mortality at 10 y but not at a median 17.7 y. PMID- 26666806 TI - In early HIV infection, immediate vs deferred antiretroviral therapy reduced serious illnesses at 3 years. PMID- 26666807 TI - In HIV-1, immediate vs deferred antiretroviral therapy and isoniazid vs no isoniazid reduced severe illness at 30 mo. PMID- 26666808 TI - Pericoital application of tenofovir gel reduced risk for herpes simplex virus type 2 in HIV-negative women. PMID- 26666809 TI - In high-risk pregnant women, an individualized lifestyle intervention reduced gestational diabetes mellitus. PMID- 26666810 TI - A modified Valsalva maneuver was more effective than standard Valsalva for treating supraventricular tachycardia. PMID- 26666811 TI - In veterans with PTSD, mindfulness-based group therapy reduced symptom severity. PMID- 26666812 TI - Optical identification of layered MoS2 via the characteristic matrix method. AB - It is demonstrated that the characteristic matrix method is effective and reliable for the optical identification of two-dimensional layered nanomaterials on different substrates. By using this method, the authors calculate the reflectivity and optical contrast of layered MoS2 crystallites prepared on quartz by chemical vapor deposition. It is found that the measured pixel intensity of an MoS2 optical image under continuous spectrum light is proportional to the calculated reflectivity, and that the theoretical optical contrast agrees well with the experimental results. This work provides a new way for the calculation of the optical contrast of the 2D nanomaterials and layered heterostructures on various substrates. PMID- 26666813 TI - Enhanced thermoelectric performance of beta-Zn4Sb3 based nanocomposites through combined effects of density of states resonance and carrier energy filtering. AB - It is a major challenge to elevate the thermoelectric figure of merit ZT of materials through enhancing their power factor (PF) and reducing the thermal conductivity at the same time. Experience has shown that engineering of the electronic density of states (eDOS) and the energy filtering mechanism (EFM) are two different effective approaches to improve the PF. However, the successful combination of these two methods is elusive. Here we show that the PF of beta Zn4Sb3 can greatly benefit from both effects. Simultaneous resonant distortion in eDOS via Pb-doping and energy filtering via introduction of interface potentials result in a ~40% increase of PF and an approximately twofold reduction of the lattice thermal conductivity due to interface scattering. Accordingly, the ZT of beta-Pb0.02Zn3.98Sb3 with 3 vol.% of Cu3SbSe4 nanoinclusions reaches a value of 1.4 at 648 K. The combination of eDOS engineering and EFM would potentially facilitate the development of high-performance thermoelectric materials. PMID- 26666814 TI - Qualities of Inpatient Hospital Rooms: Patients' Perspectives. AB - OBJECTIVES: The aim of this qualitative study was to investigate what design features of hospital rooms are valued by inpatients. BACKGROUND: Little research has explored how patients evaluate the physical environment of their hospital rooms. Most responses are captured by the Hospital Consumer Assessment of Healthcare Providers and Systems survey, which includes only two questions about the physical environment. METHOD: Two hundred thirty-six orthopedic patients (78 in the United States and 158 in Portugal) listed three features of their hospital room that influenced their level of satisfaction with their hospital stay, indicating whether the feature was positive or negative. RESULTS: The comments were more positive (71.4%) than negative (28.6%). Using the framework of supportive design from Ulrich, over half the comments (64.31%) could be categorized in one of the three dimensions: 33.2% (positive distraction), 22.4% (perceived control), and 6.0% (social support). This total includes Internet (2.7%), which could be categorized as either social support or positive distraction. Comments called "other aspects" focused on overall environmental appraisals, cleanliness, and functionality and maintenance. CONCLUSIONS: The majority of comments could be accommodated by Ulrich's theory, but it is noteworthy that other aspects emerge from patients' comments and affect their experience. Cross-cultural differences pointed to the greater role of light and sun for Portuguese patients and health status whiteboard for U.S. PATIENTS: Qualitative research can add significantly to our understanding of the healthcare experience and may inform design decisions. PMID- 26666815 TI - Effect of HPV on tumor expression levels of the most commonly used markers in HNSCC. AB - Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall 5-year survival rate is not higher than 50 %. There is much evidence that human papillomavirus (HPV) infection may influence the expression of commonly studied HNSCC markers. Our study was focused on the possible HPV specificity of molecular markers that could be key players in important steps of cancerogenesis (MKI67, EGF, EGFR, BCL-2, BAX, FOS, JUN, TP53, MT1A, MT2A, VEGFA, FLT1, MMP2, MMP9, and POU5F). qRT-PCR analysis of these selected genes was performed on 74 biopsy samples of tumors from patients with histologically verified HNSCC (22 HPV-, 52 HPV+). Kaplan-Meier analysis was done to determine the relevance of these selected markers for HNSCC prognosis. In conclusion, our study confirms the impact of HPV infection on commonly studied HNSCC markers MT2A, MMP9, FLT1, VEGFA, and POU5F that were more highly expressed in HPV negative HNSCC patients and also shows the relevance of studied markers in HPV positive and HPV-negative HNSCC patients. PMID- 26666816 TI - Overexpression of hSNF2H in glioma promotes cell proliferation, invasion, and chemoresistance through its interaction with Rsf-1. AB - hSNF2H partners with Rsf-1 to compose the Rsf complex to regulate gene expression. Recent studies indicated that hSNF2H was overexpressed in several human cancers. However, its expression pattern and biological mechanism in glioma remain unexplored. In this study, we found that hSNF2H was overexpressed in 32 % of glioma specimens. hSNF2H overexpression correlated with advanced tumor grade (p = 0.0338) and Rsf-1 positivity in glioma tissues (p = 0.016). Small interfering RNA (siRNA) knockdown was performed in A172 and U87 cell lines. MTT, colony formation assay, and cell cycle analysis showed that knockdown of hSNF2H inhibited cell proliferation, colony formation ability, and cell cycle transition. Matrigel invasion assay showed that hSNF2H depletion inhibited invasive ability of glioma cells. In addition, we demonstrated that hSNF2H depletion decreased temozolomide resistance of A172 and U87 cell lines and increased temozolomide induced apoptosis. Furthermore, hSNF2H depletion decreased cyclin D1, cyclin E, p-Rb, MMP2, cIAP1, Bcl-2 expression, and phosphorylation of IkappaBalpha and p65, suggesting hSNF2H regulates apoptosis through NF-kappaB pathway. Immunoprecipitation showed that hSNF2H could interact with Rsf-1 in both cell lines. To validate the involvement of Rsf-1, we checked the change of its downstream targets in Rsf-1 depleted cells. In Rsf-1 depleted cells, changes of cyclin E, Bcl-2, and p-IkappaBalpha were not significant using hSNF2H siRNA treatment. In conclusion, our study demonstrated that hSNF2H was overexpressed in human gliomas and contributed to glioma proliferation, invasion, and chemoresistance through regulation of cyclin E and NF-kappaB pathway, which is dependent on its interaction with Rsf-1. PMID- 26666817 TI - Silencing stem cell factor attenuates stemness and inhibits migration of cancer stem cells derived from Lewis lung carcinoma cells. AB - Stem cell factor (SCF) plays an important role in tumor growth and metastasis. However, the function of SCF in regulating stemness and migration of cancer stem cells (CSCs) remains largely undefined. Here, we report that non-adhesive culture system can enrich and expand CSCs derived from Lewis lung carcinoma (LLC) cells and that the expression level of SCF in CSCs was higher than those in LLC cells. Silencing SCF via short hairpin (sh) RNA lentivirus transduction attenuated sphere formation and inhibited expressions of stemness genes, ALDH1, Sox2, and Oct4 of CSCs in vitro and in vivo. Moreover, SCF-silenced CSCs inhibited the migration and epithelial-mesenchymal transition, with decreased expression of N cadherin, Vimentin, and increased expression of E-cadherin in vitro and in vivo. Finally, SCF-short hairpin RNA (shRNA) lentivirus transduction suppressed tumorigenicity of CSCs. Taken together, our findings unraveled an important role of SCF in CSCs derived from LLC cells. SCF might serve as a novel target for lung cancer therapy. PMID- 26666818 TI - Breast cancer risk in relation to TP53 codon 72 and CDH1 gene polymorphisms in the Bangladeshi women. AB - Pharmacogenomic studies play a significant role in understanding the risk of breast cancer where genetic abnormalities are implicated as the etiology of cancer. Various polymorphisms of tumor suppressor gene TP53 and E-cadherin (CDH1) have been found to be associated with increased breast cancer risk worldwide. This study aimed to analyze the contribution of TP53 and CDH1 gene anomalies in breast cancer risk in the Bangladeshi breast cancer patients. For risk determination, 310 patients with breast cancer and 250 controls from Bangladeshi women were recruited who are matched up with age and use of contraceptives with patients. Genetic polymorphisms were detected by using polymerase chain reaction restriction fragment length polymorphism. A significant association was found between TP53Arg72Pro (rs1042522) and CDH1 -160 C/A (rs16260) polymorphisms and breast cancer risk. In case of P53rs1042522 polymorphism, Arg/Pro (P = 0.0053, odds ratio (OR) = 1.69) and Pro/Pro (P = 0.018, OR = 1.83) genotypes were associated with increased risk of breast cancer in comparison to the Arg/Arg genotype. Arg/Pro + Pro/Pro genotype and Pro allele also increased the risk of breast cancer (P = 0.002, OR = 1.73; P = 0.004, OR = 1.43, respectively). In case of CDH1rs16260 polymorphism, C/A heterozygote and combined C/A + A/A genotypes were found to be strongly associated (P = 0.005, OR = 1.67; P = 0.0037, OR = 1.68) with increased risk of breast cancer. The variant A allele also increased the breast cancer risk (P = 0.0058, OR = 1.52). The present study demonstrates that P53Arg72Pro and CDH1rs16260 polymorphisms are associated with elevated breast cancer risk in the Bangladeshi population. PMID- 26666819 TI - Association of HER2 codon 655 polymorphism with ovarian cancer. AB - The role of the human epidermal growth factor receptor 2 (HER2) codon 655 (Ile655Val) polymorphism in ovarian cancer is not fully understood. Two studies indicated a possible association between the Val allele and elevated risk or reduced prognosis of ovarian cancer. We investigated the HER2 codon 655 (rs1136201) polymorphism in 242 Austrian women-142 ovarian cancer patients and 100 healthy controls-by polymerase chain reaction and pyrosequencing. Associations between Ile655Val polymorphism and clinicopathological variables (e.g., age, FIGO stage, grading, serous vs. non-serous histology) were evaluated. The genotype distributions in ovarian cancer patients and controls were: AA; 66.2 %, AG; 25.35 %, GG; 8.45 %, and AA; 63 %, AG; 34 %, GG; 3.7 %, respectively (OR 1.15, CI 95 % 0.67-1.96). We observed a non-significant trend toward elevated cancer risk in Val/Val genotype (OR 2.98, CI 95 % 0.82-10.87, p = 0.10). Of note, 11 out of 12 Val/Val homozygotes were postmenopausal. The link between the Val/Val homozygosity and age over 50 years at diagnosis (OR 0.15, CI 95 % 0.02 1.2) was barely significant (p = 0.056). Summarizing, our data indicated a non significant trend toward increased ovarian cancer risk in the Val/Val homozygosity, especially in women aged above 50 years. Further large-cohort studies focusing on the role of the HER2 codon 655 Val allele are needed. PMID- 26666820 TI - MiRNA-21 induces epithelial to mesenchymal transition and gemcitabine resistance via the PTEN/AKT pathway in breast cancer. AB - Acquisition of gemcitabine resistance in breast cancer has not been fully clarified. Prior studies suggest that miRNAs are important to chemoresistance in solid tumors and we confirmed that miR-21 is involved in the development of gemcitabine resistance. Epithelial-to-mesenchymal transition (EMT) and AKT pathway activation were noted to be important to this resistance as well. PTEN, a direct target gene of miR-21, was significantly downregulated in gemcitabine resistant breast cancer cells and restoration of PTEN expression blocked miR-21 induced EMT and gemcitabine resistance. Our data offer novel insight into gemcitabine resistance in breast cancer and suggest that miR-21 may be used to predict optimal breast cancer therapy and may be a potential therapeutic target for reversing gemcitabine resistance. PMID- 26666821 TI - The effect of Vasohibin-1 expression and tumor-associated macrophages on the angiogenesis in vitro and in vivo. AB - Vasohibin-1 is an intrinsic inhibitor of angiogenesis induced by VEGF-A. However, there little is known about the relationship between Vasohibin-1 expression, angiogenesis, and tumor-associated macrophages (TAMs). Vasohibin-1 expression, VEGF-A expression, microvessel density (MVD) marked with CD34, and density of cells marked with CD68 were measured in 111 paraffin-embedded tissues of gastric cancer by immunohistochemistry. The length of tube forming structures of endothelial cells and mobility rate of gastric cancer cells in Matrigel were tested by three-dimensional live cell imaging system. The effect of TAMs on the tumor growth, MVD, and Vasohibin-1 expression was measured by nude mice tumor genesis assay in vivo. We found that high Vasohibin-1 protein expression correlated significantly with worse TNM stage (P = 0.002), metastatic lymph node (P = 0.014), distant metastasis (P = 0.022), overall survival (P < 0.001), and progression-free survival (P < 0.001) compared to those with low Vasohibin-1 expression. Vasohibin-1 protein expression had statistical correlation with the MVD (r = 0.860, P < 0.001), density of CD68(+) cells (r = 0.882, P < 0.001), and VEGF-A expression (r = 0.719, P < 0.001) in the gastric cancer tissues. Decreasing Vasohibin-1 expression with siRNA increased the length of tube forming structures of endothelial cells in co-culture with endothelial cells (EA-hy923), macrophages, and gastric cancers (Hs746T). Tumor volume (P = 0.001), Vasohibin-1 (P < 0.001), and VEGF-A (P < 0.001) expression in mice inoculated with AGS and THP (10:1) was significantly higher than that with AGS alone (P = 0.001). Vasohibin-1 protein expression had statistical correlation with VEGF expression (r = 0.786, P < 0.001) and MVD (r = 0.496, P = 0.014) in gastric xenografted tumor. Therefore, Vasohibin-1 might be a potential marker of worse prognosis and therapeutic target in gastric cancer. Vasohibin-1 might play an important role in the process of angiogenesis regulated by TAMs. PMID- 26666822 TI - Clinicopathological significance of p38beta, p38gamma, and p38delta and its biological roles in esophageal squamous cell carcinoma. AB - P38beta, p38gamma, and p38delta have been sporadically and scarcely reported to be involved in the carcinogenesis of cancers, compared with p38alpha isoform. However, little has been known regarding their clinicopathological significance and biological roles in esophageal squamous cell carcinoma (ESCC). Expression status of p38beta, p38gamma, and p38delta was assayed using immunohistochemistry with ESCC tissue microarray; ensuing clinicopathological significance was statistically analyzed. To define its biological roles on proliferation, migration and invasion of ESCC cell line Eca109 in vitro, MTT, wound healing, and Transwell assays were employed, respectively. As confirmation, athymic nude mice were taken to verify the effect over proliferation in vivo. It was found that both p38beta and p38delta expression, other than p38gamma, were significantly higher in ESCC tissues compared with paired normal controls. In terms of prognosis, only p38beta expression was observed to be significantly associated with overall prognosis. Clinicopathologically, there was significant association between p38gamma expression and clinical stage, lymph nodes metastases, and tumor volume. No significant association was found for p38beta and p38delta between its expression and other clinicopathological parameters other than significant difference of expression between ESCC versus normal control. In Eca109, it was observed that p38beta, p38gamma, and p38delta can promote the cell growth and motility. As verification, over-expression of p38delta can promote, whereas knockdown of p38gamma can prevent, the tumorigenesis in nude mice model xenografted with Eca109 cells whose basal level of p38delta was stably over expressed and p38gamma was stably knocked down. Together, our results demonstrate that p38beta, p38gamma, and p38delta played oncogenic roles in ESCC. PMID- 26666823 TI - LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation. AB - Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The multikinase inhibitor sorafenib is the only clinically proved systematic treatment for HCC. However, few patients respond to sorafenib. Hypoxic microenvironments contribute to sorafenib resistance. LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor was previously found to be a chemosensitizer in HCC. Here, we tested whether LB-100 could sensitize HCC to the effects of sorafenib. Intriguingly, LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells. We further proved that PP2A mediated LB-100-induced p Smad3 overexpression. In addition, p38 mitogen-activated protein kinase pathway was activated in hypoxic conditions, and enhanced p-Smad3-dependent Bcl-2 inhibition and consequent apoptosis. In conclusion, LB-100 sensitized HCC cells to sorafenib in hypoxic environments. This effect was mediated by inactivation of PP2A, resulting in enhanced level of p-Smad3. Increased p-Smad3 downregulated Bcl 2, causing increased apoptosis of HCC cells. PMID- 26666824 TI - Up-regulation of SRPK1 in non-small cell lung cancer promotes the growth and migration of cancer cells. AB - Dys-regulation of serine-arginine protein kinase 1 (SRPK1) has been reported in non-small cell lung cancer (NSCLC). However, its functions in the progression of NSCLC remain poorly understood. In this study, the expression of SRPK1 in NSCLC tissues was determined using real-time PCR, and the roles of SRPK1 in the progression of NSCLC were investigated. It was found that both the mRNA level and the protein level of SRPK1 were up-regulated in NSCLC tissues. Forced expression of SRPK1 promoted the growth and migration of NSCLC cells, while knocking down the expression of SRPK1 inhibited the growth, migration, and tumorigenicity of NSCLC cells. Mechanism studies showed that SRPK1 activated the transcriptional activity of beta-catenin/T-cell factor (TCF) complex, and knocking down the expression of SRPK1 attenuated the expression of target genes of beta-catenin/T cell factor (TCF) complex. In addition, silencing the expression of SRPK1 down regulated the phosphorylation of GSK3beta. Taken together, SRPK1 might play an oncogenic role in NSCLC, and SRPK1 might be a therapeutic target for NSCLC. PMID- 26666825 TI - A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients. AB - Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness. PMID- 26666826 TI - A novel therapeutic approach against B-cell non-Hodgkin's lymphoma through co inhibition of Hedgehog signaling pathway and autophagy. AB - B-cell non-Hodgkin's lymphoma (B-NHL) is one of the most common types of cancer in the world, with half of the patients dying due to the resistance or tolerance against the treatment. Thus, a novel therapeutic approach for B-NHL treatment was urgently needed. In this study, we investigated the potential of co-inhibition of Hedgehog signaling pathway (Hh) and autophagy in B-NHL therapy. We reported that vismodegib, an inhibitor of Hedgehog signaling pathway, could block the Hh pathway and induce cytotoxicity and apoptosis in B-NHL Raji cells. During this process, autophagy was activated as a response to Hh inhibition. Importantly, inhibition of autophagy potentiated the cytotoxicity and caspase 3-dependent apoptosis induced by vismodegib in B-NHL cells. Furthermore, clearance of ROS generation caused a decreased activity of autophagy and attenuated cytotoxicity in vismodegib-treated cells, while inhibition of autophagy accelerated the formation of ROS, indicating that ROS was required for vismodegib-induced autophagy and cytotoxicity in B-NHL cells. Our results demonstrated that co inhibition of Hh pathway and autophagy could potently kill B-NHL cells and highlighted a novel approach for B-NHL therapy by co-inhibition of Hh pathway and cytoprotective autophagy. PMID- 26666828 TI - A zeolite CAN-type aluminoborate with gigantic 24-ring channels. AB - A cancrinite type aluminoborate with gigantic 24-ring channels has been made under solvothermal conditions using Al(i-PrO)3 as the Al source and amines as the structure directing agents. Its framework is alternately constructed from B5O10 clusters and AlO4 units, no Al-O-Al linkages exist in the structure. Notably, the wall of the 24-ring channels has odd 11-ring windows, resulting in an unprecedented 3D intersecting channel system. PMID- 26666827 TI - Tick-borne zoonotic pathogens in birds in Guangxi, Southwest China. AB - BACKGROUND: Wildlife is an important natural reservoir of many tick-borne pathogens. These agents have an impact on the health of humans and other animals throughout the world. This study was conducted to determine whether and what species of tick-borne agents had infected wild birds collected from Guangxi, in southwest China. FINDINGS: Liver samples obtained from wild birds were tested for the presence of tick-borne pathogens by PCR assays and sequencing of the flagellin and 16S rRNA genes. Borrelia garinii was detected in Eurasian collared doves (2/57, 3.5%) from among the 95 wild birds. Anaplasma phagocytophilum was detected in Eurasian collared doves (2/57, 3.5%) and Eurasian eagle owls (2/13, 15.4%). Ehrlichia chaffeensis and a potential novel Anaplasma sp. were identified in Common pheasant (1/12, 8.3%). These results suggest the involvement of birds in the cycle of tick-borne diseases. To our knowledge, this is the first study to document infection of birds with B. garinii, A. phagocytophilum, E. chaffeensis and the novel Anaplasma sp. in China. CONCLUSIONS: Tick-borne zoonotic bacteria B. garinii, A. phagocytophilum and E. chaffeensis, and a potential novel Anaplasma sp., were identified in wild birds in southwest China. The presence of these agents in birds increases the potential spread over long distances and the risk of transmission of infection from birds to new hosts, including humans. PMID- 26666830 TI - Organoids derived from digestive tract, liver, and pancreas. AB - Lgr5 marks stem cells in digestive epithelial tissues by lineage tracing, and in vitro ever-expansion of Lgr5 stem cells form organoids, which can be directed to differentiate into functional somatic cells. Organoids derived from gastrointestinal epithelium even recapitulate the morphologic features of their in vivo counterpart. Culture conditions are also modified to establish cancer organoids from individual patients. With great genetic stability during derivation and expansion, organoids retain either single mutation in patients with inherited disease or multiple mutations of cancer tissues. Together with efficient gene-editing protocol, organoids are emerging as powerful in vitro disease models. PMID- 26666829 TI - SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients. AB - BACKGROUND: Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship. METHODS: The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. RESULTS: Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01-1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00-1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00-1.21). CONCLUSION: SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies. PMID- 26666831 TI - Heat shock proteins 27 and 70 contribute to the protection of Schisandrin B against d-galactosamine-induced liver injury in mice. AB - Schisandrin B is a hepatoprotective component isolated from a traditional Chinese herb, Schisandra chinensis (Turcz.) Baill. This study determined the effect of Schisandrin B on d-galactosamine -induced liver injury and the role of heat shock proteins 27 and 70 against liver injury in mice. Acute liver injury was induced by intraperitoneal injection of d-galactosamine to mice, and Schisandrin B was given orally. The protein and gene expression of heat shock proteins 27 and 70 were detected by western blot and real-time quantitative polymerase chain reaction, respectively. Liver tissues were subjected to histological evaluation, and the activities of alanine aminotransferase and aspartate aminotransferase in the serum were measured. Pretreatment of Schisandrin B significantly attenuated d galactosamine-induced liver injury in mice. This result was evidenced by improved alteration of histopathological hepatic necrosis and reduced alanine aminotransferase and aspartate aminotransferase activities in the serum. The hepatoprotective effect was accompanied with overexpression of heat shock proteins 27 and 70 both at the protein and mRNA levels. However, the aforementioned actions of Schisandrin B were all markedly suppressed by the heat shock protein inhibitor quercetin. Heat shock proteins 27 and 70 were involved in the protective effect of Schisandrin B against d-galactosamine-induced liver injury in mice. PMID- 26666833 TI - Familiarity modulates motor activation while other species' actions are observed: a magnetic stimulation study. AB - Observing other people's actions facilitates the observer's motor system as compared with observing the same individuals at rest. This motor activation is thought to result from mirror-like activity in fronto-parietal areas, which enhances the excitability of the primary motor cortex via cortico-cortical pathways. Although covert motor activation in response to observed actions has been widely investigated between conspecifics, how humans cope with other species' actions has received less attention. For example, it remains unclear whether the human motor system is activated by observing other species' actions, and whether prior familiarity with the non-conspecific agent modulates this activation. Here, we combined single-pulse transcranial magnetic stimulation and motor-evoked potential recording to explore the impact of familiarity on motor activation during the observation of non-conspecific actions. Videos displaying actions performed either by a conspecific (human) or by a non-conspecific (dog) were shown to individuals who had prior familiarity or no familiarity at all with the non-conspecific agent. We found that, whereas individuals with long-lasting familiarity showed similar levels of motor activation for human and canine actions, individuals who had no familiarity showed higher motor activation for human than for canine actions. These findings suggest that the human motor system is flexible enough to resonate with other species, and that familiarity plays a key role in tuning this ability. PMID- 26666834 TI - Intraoperative identification of the human communicating nerve during thyroidectomy. AB - The human communicating nerve (HCN) is a connection between the superior and recurrent laryngeal nerves that has been described in cadaveric studies. We report a case of an extralaryngeal variant of the HCN that was identified and stimulated intraoperatively during thyroidectomy. This appears to be the first case of intraoperative identification of this anatomic variant, of which the functional significance remains unclear. PMID- 26666832 TI - SCF(beta-TRCP) promotes cell growth by targeting PR-Set7/Set8 for degradation. AB - The Set8/PR-Set7/KMT5a methyltransferase plays critical roles in governing transcriptional regulation, cell cycle progression and tumorigenesis. Although CRL4(Cdt2) was reported to regulate Set8 stability, deleting the PIP motif only led to partial resistance to ultraviolet-induced degradation of Set8, indicating the existence of additional E3 ligase(s) controlling Set8 stability. Furthermore, it remains largely undefined how DNA damage-induced kinase cascades trigger the timely destruction of Set8 to govern tumorigenesis. Here, we report that SCF(beta TRCP) earmarks Set8 for ubiquitination and degradation in a casein kinase I dependent manner, which is activated by DNA-damaging agents. Biologically, both CRL4(Cdt2) and SCF(beta-TRCP)-mediated pathways contribute to ultraviolet-induced Set8 degradation to control cell cycle progression, governing the onset of DNA damage-induced checkpoints. Therefore, like many critical cell cycle regulators including p21 and Cdt1, we uncover a tight regulatory network to accurately control Set8 abundance. Our studies further suggest that aberrancies in this delicate degradation pathway might contribute to aberrant elevation of Set8 in human tumours. PMID- 26666835 TI - Detection of Virulence Genes and Growth Potential in Listeria monocytogenes Strains Isolated from Ricotta Salata Cheese. AB - Ricotta Salata is a traditional ripened and salted whey cheese made in Sardinia (Italy) from sheep's milk. This product is catalogued as ready-to-eat food (RTE) since it is not submitted to any further treatment before consumption. Thus, foodborne pathogens, such as Listeria monocytogenes, can represent a health risk for consumers. In September 2012, the FDA ordered the recall of several batches of Ricotta Salata imported from Italy linked to 22 cases of Listeriosis in the United States. This study was aimed at evaluating the presence and virulence properties of L. monocytogenes in 87 samples of Ricotta Salata produced in Sardinia. The ability of this product to support its growth under foreseen packing and storing conditions was also evaluated in 252 samples. Of the 87 samples 17.2% were positive for the presence of L. monocytogenes with an average concentration of 2.2 log10 cfu/g. All virulence-associated genes (prfA, rrn, hlyA, actA, inlA, inlB, iap, plcA, and plcB) were detected in only one isolated strain. The Ricotta Salata samples were artificially inoculated and growth potential (delta) was assessed over a period of 3 mo. The value of the growth potential was always >0.5 log10 cfu/g under foreseen packing and storing conditions. This study indicates that Ricotta Salata supports the L. monocytogenes growth to levels that may present a serious risk to public health, even while stored at refrigeration temperatures. PMID- 26666836 TI - Promising reciprocity: When proposing a favor for a request increases compliance even if the favor is not accepted. AB - Research has reported that reciprocity is an important social norm in relationships. In previous studies on reciprocity, participants' behavior was examined after receiving a favor from someone. In a series of field studies, we examined the effect of a statement that proved that a solicitor was someone who respected this principle. Confederates solicited participants for money or a cigarette in exchange for stamps or money, respectively. It was found that the participants complied more readily with the request in the promised favor condition, but most of them refused to take the promised favor. We conclude that individuals were led to help those who respected the putative norm of reciprocity in their social interaction. PMID- 26666838 TI - Review: Spreading the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein. AB - Synucleinopathies are characterized by abnormal proteinaceous aggregates, mainly composed of fibrillar alpha-synuclein (alpha-syn). It is now believed that alpha syn can form small aggregates in a restricted number of cells, that propagate to neighbouring cells and seed aggregation of endogenous alpha-syn, in a 'prion-like manner'. This process could underlie the stereotypical progression of Lewy bodies described by Braak and colleagues across different stages of Parkinson's disease (PD). This prion-like behaviour of alpha-syn has been recently investigated in animal models of PD or multiple system atrophy (MSA). These models investigate the cell-to-cell transfer of alpha-syn seeds, or the induction and spreading of alpha-syn pathology in transgenic or wild-type rodent brain. In this review, we first outline the involvement of alpha-syn in Lewy body diseases and MSA, and discuss how 'prion-like' mechanisms can contribute to disease. Thereon, we debate the relevance of animal models used to study prion-like propagation. Finally, we review current main histological methods used to assess alpha-syn pathology both in animal models and in human samples and their relevance to the disease. Specifically, we discuss using alpha-syn phosphorylated at serine 129 as a marker of pathology, and the novel methods available that allow for more sensitive detection of early pathology, which has relevance for modelling synucleinopathies. PMID- 26666837 TI - The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis. AB - Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95% CI:1.11-1.58) and co-dominant models (OR = 1.24, 95% CI:1.02-1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95% CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke. PMID- 26666839 TI - Expanding the computational toolbox for interrogating cancer kinomes. PMID- 26666840 TI - Intracranial pressure, its components and cerebrospinal fluid pressure-volume compensation. AB - Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant-rate infusion study. Due to the dynamic nature of ICP, a 'snapshot' manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure-volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction. PMID- 26666841 TI - The influence of type of inhalation device on adherence of COPD patients to inhaled medication. AB - OBJECTIVE: To study the influence of type of inhalation device on medication adherence of COPD patients. METHODS: Adherence to inhalation medication of 795 patients was recorded from pharmacy records over 3 years. It was expressed as percentage and deemed good at >= 75-<= 125%, sub-optimal >= 50-<75%, and poor <50% (underuse) or >125% (overuse). Since most patients used more than one device, 1379 medication periods were analyzed. RESULTS: Patients using a Metered Dose Inhaler (MDI) or Diskus had a 2.3-fold and 2.2-fold increased risk, respectively, of suboptimal adherence versus good adherence, compared to Handihaler and a 2.1-fold and 2.2-fold increased risk, respectively, of underuse versus good adherence compared to Handihaler. Turbuhaler, MDI, Respimat had a 7.9 fold, 3.5-fold, and 2.0-fold increased risk, of overuse versus good adherence compared to Handihaler. CONCLUSIONS: In COPD, adherence to inhalation medication is device-related. Overuse was most pronounced for devices without a dose counter, devices with the ability to load a dosage without actual inhalation, or devices lacking feedback of correct inhalation. The design of the device seems to be related to underuse and overuse of inhaled medication. Future research might investigate whether prescribing a different device with similar medication improves therapy adherence. PMID- 26666842 TI - Surface Plasmon Polariton Graphene Photodetectors. AB - The combination of plasmonic nanoparticles and graphene enhances the responsivity and spectral selectivity of graphene-based photodetectors. However, the small area of the metal-graphene junction, where the induced electron-hole pairs separate, limits the photoactive region to submicron length scales. Here, we couple graphene with a plasmonic grating and exploit the resulting surface plasmon polaritons to deliver the collected photons to the junction region of a metal-graphene-metal photodetector. This gives a 400% enhancement of responsivity and a 1000% increase in photoactive length, combined with tunable spectral selectivity. The interference between surface plasmon polaritons and the incident wave introduces new functionalities, such as light flux attraction or repulsion from the contact edges, enabling the tailored design of the photodetector's spectral response. This architecture can also be used for surface plasmon biosensing with direct-electric-redout, eliminating the need of bulky optics. PMID- 26666843 TI - Low-Temperature Selective Growth of Tungsten Oxide Nanowires by Controlled Nanoscale Stress Induction. AB - We report a unique approach for the patterned growth of single-crystalline tungsten oxide (WOx) nanowires based on localized stress-induction. Ions implanted into the desired growth area of WOx thin films lead to a local increase in the compressive stress, leading to the growth of nanowire at lower temperatures (600 degrees C vs. 750-900 degrees C) than for equivalent non implanted samples. Nanowires were successfully grown on the microscale patterns using wafer-level ion implantation and on the nanometer scale patterns using a focused ion beam (FIB). Experimental results show that nanowire growth is influenced by a number of factors including the dose of the implanted ions and their atomic radius. The implanted-ion-assisted, stress-induced method proposed here for the patterned growth of WOx nanowires is simpler than alternative approaches and enhances the compatibility of the process by reducing the growth temperature. PMID- 26666844 TI - Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP. AB - We use quantum mechanical and molecular mechanical (QM/MM) simulations to study ATP hydrolysis catalyzed by the maltose transporter. This protein is a prototypical member of a large family that consists of ATP-binding cassette (ABC) transporters. The ABC proteins catalyze ATP hydrolysis to perform a variety of biological functions. Despite extensive research efforts, the precise molecular mechanism of ATP hydrolysis catalyzed by the ABC enzymes remains elusive. In this work, the reaction pathway for ATP hydrolysis in the maltose transporter is evaluated using a QM/MM implementation of the nudged elastic band method without presuming reaction coordinates. The potential of mean force along the reaction pathway is obtained with an activation free energy of 19.2 kcal/mol in agreement with experiments. The results demonstrate that the reaction proceeds via a dissociative-like pathway with a trigonal bipyramidal transition state in which the cleavage of the gamma-phosphate P-O bond occurs and the O-H bond of the lytic water molecule is not yet broken. Our calculations clearly show that the Walker B glutamate as well as the switch histidine stabilizes the transition state via electrostatic interactions rather than serving as a catalytic base. The results are consistent with biochemical and structural experiments, providing novel insight into the molecular mechanism of ATP hydrolysis in the ABC proteins. PMID- 26666845 TI - Cow's milk protein allergy and common gastrointestinal symptoms in infants. PMID- 26666846 TI - Organoids and the genetically encoded self-assembly of embryonic stem cells. AB - Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to self organization, as often suggested, but rather to a process of genetically encoded self-assembly where genetic programs encode and control the emergence of biological structures. PMID- 26666847 TI - Pharmaceuticals in the environment--Global occurrences and perspectives. AB - Pharmaceuticals are known to occur widely in the environment of industrialized countries. In developing countries, more monitoring results have recently become available, but a concise picture of measured environmental concentrations (MECs) is still elusive. Through a comprehensive literature review of 1016 original publications and 150 review articles, the authors collected MECs for human and veterinary pharmaceutical substances reported worldwide in surface water, groundwater, tap/drinking water, manure, soil, and other environmental matrices in a comprehensive database. Due to the heterogeneity of the data sources, a simplified data quality assessment was conducted. The database reveals that pharmaceuticals or their transformation products have been detected in the environment of 71 countries covering all continents. These countries were then grouped into the 5 regions recognized by the United Nations (UN). In total, 631 different pharmaceutical substances were found at MECs above the detection limit of the respective analytical methods employed, revealing distinct regional patterns. Sixteen substances were detected in each of the 5 UN regions. For example, the anti-inflammatory drug diclofenac has been detected in environmental matrices in 50 countries, and concentrations found in several locations exceeded predicted no-effect concentrations. Urban wastewater seems to be the dominant emission pathway for pharmaceuticals globally, although emissions from industrial production, hospitals, agriculture, and aquaculture are important locally. The authors conclude that pharmaceuticals are a global challenge calling for multistakeholder approaches to prevent, reduce, and manage their entry into and presence in the environment, such as those being discussed under the Strategic Approach to International Chemicals Management, a UN Environment Program. PMID- 26666848 TI - Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database. AB - BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral lipid storage disorder characterised by progressive, disabling neurological symptoms and premature death in most patients. During the last decade, national cohort studies have accrued a great deal of data on the symptomatology and natural history of NP-C. METHODS: In an observational cohort study, we present a substantial update based on the clinical presentation and follow-up of all known UK-based patients with a confirmed diagnosis of NP-C who have been tracked on an electronic database at the Department of Genetic Medicine, University of Manchester, UK. Patients were stratified according to accepted age-at neurological-onset categories. Data on patients' clinical signs and symptoms, medical history and genetic studies are summarised using descriptive methods. RESULTS: A total of 146 patients with NP-C were included, representing the full known UK NP-C cohort, as observed from database information between 1999 and the end of 2011: 72 patients (49 %) were alive at the end of the observation period. Among a total of 116 patients (79 %) who possessed at least one identified, disease-causing NP-C gene mutation, 114 (98 %) had NPC1 and two (2 %) had NPC2 mutations. Overall, 53/194 (27 %) identified mutations were novel. Six patients (4 %) had an early, non-neurological neonatal onset form of NP-C. The numbers (%) of patients with accepted age-at-neurological onset forms were: 8 (5 %) early infantile onset, 51 (35 %) late-infantile onset, 42 (29 %) juvenile onset, and 25 (17 %) adolescent/adult onset. Fourteen patients diagnosed based on visceral symptoms and/or sibling history, confirmed in most cases by genetic analysis, did not have any neurological manifestations at last follow up (11 patients with mean [SD] age at last follow up 2.5 [1.8] years: 3 with mean [SD] age at death 20.8 [15.9] years). A total of 51 patients (35 %) received miglustat therapy. The mean (SD) overall treatment duration up to the end of the observation period was 2.6 (2.3) years. CONCLUSIONS: This UK cohort is the largest national NP-C cohort reported to date, and confirms the wide phenotypic variability of the disease, as reported in other countries. Further analyses are required to assess the impact of miglustat therapy on neurological disease progression. PMID- 26666850 TI - The use of lasers for direct pulp capping. AB - Direct pulp capping helps extend the life of a diseased tooth by maintaining tooth vitality. Nowadays, lasers are more frequently used during direct pulp capping in the clinic, but their use has not been previously reviewed. This review presents the basic properties of currently available lasers, scientific evidence on the effects of laser application on direct pulp capping, and future directions for this technology. An extensive literature search was conducted in various databases for articles published up to January 2015. Original in vitro, in vivo, and clinical studies, reviews, and book chapters published in English were included. Various laser systems have been increasingly and successfully applied in direct pulp capping. Lasers offer excellent characteristics in terms of hemostasis and decontamination for field preparation during direct pulp capping treatment; however, the sealing of exposed pulp with one of the dental materials, such as calcium hydroxide, mineral trioxide aggregates, and bonded composite resins, is still required after laser treatment. Clinicians should consider the characteristics of each wavelength, the emission mode, irradiation exposure time, power, type of laser tip, and the distance between the laser tip and the surface being irradiated. PMID- 26666849 TI - Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-alpha-induced hepatic insulin resistance. AB - Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorly understood. The objective of this study was to estimate the role of PP4 in tumor necrosis factor (TNF)-alpha-induced hepatic insulin resistance. db/db mice and TNF-alpha treated C57BL/6J mice were used as hepatic insulin resistance animal models. In vitro models were established in both HepG2 cells and primary hepatocytes by TNF alpha treatment. We found that increased expression and activity of PP4 occurred in the livers of db/db mice and TNF-alpha-induced hepatic insulin resistance both in vitro and in vivo. Actually, PP4 silencing and suppression of PP4 activity ameliorated TNF-alpha-induced hepatic insulin resistance, whereas over-expression of PP4 caused insulin resistance. We then further investigated the prodiabetic mechanism of PP4 in TNF-alpha-induced insulin resistance. We found that PP4 formed a complex with IRS-1 to promote phosphorylation of IRS-1 on serine 307 via JNK activation and reduce the expression of IRS-1. Thus, PP4 is an important regulator in inflammatory related insulin resistance. PMID- 26666851 TI - Comparative study of cytokeratin and langerin expression in keratinized cystic lesions of the oral and maxillofacial regions. AB - Dermoid cysts (DMCs) and epidermoid cysts (EDMCs) usually arise in soft tissues, whereas orthokeratinized odontogenic cysts (OOCs) and keratocystic odontogenic tumors (KCOTs) develop in the jaw. In this study, we performed immunohistochemical analysis of cytokeratins (CKs) to examine differences in the lining epithelium of DMCs, EDMCs, OOCs, and KCOTs. In addition, we carried out immunohistochemical examination of langerin to clarify the biological characteristics of the orthokeratinized lining epithelium of DMCs, EDMCs, and OOCs. Seven DMCs, 30 EDMCs, 11 OOCs, and 28 KCOTs were examined immunohistochemically using antibodies against CK10, 13, 14, 16, 17, 19, and langerin. Immunoreactivities for CKs and langerin in oral DMCs and EDMCs were similar to those of lesions affecting the skin. Positive reactivity for CK13 and 17 was evident in OOCs, but not in DMCs/EDMCs. CK10 was significantly positive in all layers except for the basal layer in OOCs, but was negative in KCOTs. CK17 was positive in all layers in KCOTs, and in all layers except for the basal layer in both OOCs and dentigerous cysts. CK19 was negative in OOCs. Langerhans cells were found mainly in OOCs, but were hardly evident in KCOTs. These results suggest that DMCs/EDMCs, OOCs and KCOTs are independent diseases. PMID- 26666852 TI - Telomerase activity in the occurrence and progression of oral squamous cell carcinoma. AB - Chronic inflammation is considered to be one of the risk factors for carcinogenesis. It was recently reported that telomerase plays an important role in inducing such chronic inflammation. Although high telomerase activity is detected in cancer tissues, the activator of telomerase is still unknown. In this study, we used an immunohistochemical method to examine the expression of human telomerase reverse transcriptase (hTERT) in the dysplasia-carcinoma sequence in the oral cavity. Furthermore, the effects of inflammatory cytokines on the telomerase activity and migration of oral cancer cell lines (Ca9-22, HSC-3, and HSC-4) were examined. Immunoreactivity for hTERT was observed in squamous intraepithelial neoplasia 3 and squamous cell carcinoma. Telomerase activity in Ca9-22 cells was increased by treatment with TNF-alpha and INF-gamma, while its activity in HSC-4 cells was decreased by IL-1beta. Although inflammatory cytokines did not affect the proliferative activity of any of the oral cancer cell lines, cytokines and hTERT siRNA promoted the migration of HSC-3 cells. These results suggest that the presence of long-term chronic inflammation may increase telomerase activity and therefore contribute to malignant transformation of the oral mucosal epithelium. Furthermore, inhibition of telomerase activity by inflammatory stimuli increases the invasion of certain types of oral squamous cell carcinomas. PMID- 26666853 TI - Effect of ionomycin on interaction of calnexin with vesicular stomatitis virus glycoprotein is cell type-specific. AB - Ionomycin is a calcium ionophore that induces release of calcium ions (Ca(2+)) from cellular storage to cytoplasm and Ca(2+) influx from the outside of the cell. We investigated the effect of ionomycin on endoplasmic reticulum (ER)-Golgi transport in the vesicular stomatitis virus glycoprotein (VSV-G) system. Ionomycin inhibited transport of VSV-G in a concentration-dependent manner in baby hamster kidney (BHK) cells and HeLa cells. Half-maximum inhibition was observed at 5 MUM. The inhibitory effect of ionomycin was not dependent on the cytoplasmic portion. Chelation of Ca(2+) in culture medium did not affect transport efficiency, but co-incubation with ionomycin completely shut off transport. These findings highlight the importance of Ca(2+) release from cellular storage. Because the inhibitory effect of ionomycin was expected to be dependent on mutual interaction of VSV-G and the ER chaperone calnexin, we further investigated interaction kinetics. In HeLa cells but not BHK cells the interaction of VSV-G and calnexin was prolonged in the presence of ionomycin. Taken together, the present results indicate that, by releasing Ca(2+) from cellular storage, ionomycin inhibits ER-Golgi transport by interfering with the release of VSV-G from calnexin in HeLa cells. A mechanism of cell type-dependent ER-Golgi transport regulation was revealed. PMID- 26666854 TI - Temporal expression in rats of receptor tyrosine kinase Tie2 during early wound healing after tooth extraction. AB - We examined the role of Tie2 in regulating wound healing after tooth extraction. Wistar rats underwent maxillary incisor tooth extraction, and immunodetection techniques were used to determine Tie2 expression in the healing wound. The wound was initially filled with blood coagulum containing densely aggregated erythrocytes, leukocytes, fibrin, and endothelial progenitor cells, indicating that blood vessel formation started in the socket. Tie2 was detected on monocytic cell membranes. On day 3, fibroblastic cells proliferated in the coagulum, small vessels appeared by day 5, and new bone formed in the vessel-rich area. Robust woven bone trabeculae were present around vessels by day 7, and woven bone and osteoclast-like giant cells were present on day 10. Woven bone surrounded sinusoidal capillary-like vessels. Full-length (140-160 kDa) Tie2 was not detected at any time, although Tie2 fragments were present in the healing wound. N-terminus- and C-terminus-specific Tie2 antibodies detected 40-kDa and 60-kDa fragments or 70-kDa and 50-kDa fragments, respectively. The levels of these fragments decreased during the first 3 days and started to increase by day 5-10. The Tie2 extracellular domain initially inhibited angiogenesis, and its degradation relieved inhibition of new vessel formation. The onset of vessel formation in the wound may be induced by scattered endothelial progenitor cells. PMID- 26666855 TI - RUNX2 expression during early healing of tooth-extraction wounds in rats. AB - Determining the molecular mechanisms involved in the healing of wounds created by tooth extraction will likely increase understanding of jawbone healing after dental surgery. Runt-related transcription factor 2 (RUNX2) is required for mesenchymal stem cells to differentiate to osteoprogenitor cells. Therefore, we used a rat model to analyze RUNX2 expression during wound-socket healing after tooth extraction. Immunohistochemical analyses of wound tissue immediately after tooth extraction revealed RUNX2 expression in monocytic cells in the coagulum and, to a lesser extent, in remnants of the periodontal ligament. Shortly thereafter, fibroblastic cells proliferated in the coagulum and large polymorphic cells were enclosed within the newly formed bone matrix. Western blot analysis showed that RUNX2 expression peaked from 12 h to 1 day after extraction and then rapidly declined. These findings indicate that the osteogenic commitment of cells derived from hematopoietic tissue in the extraction wound was greater than that of cells in remnants of the periodontal ligament. Thus, cells derived mainly from hematopoietic tissue and RUNX2 expression are essential in the differentiation of mesenchymal stem cells to osteoprogenitor cells immediately after tooth extraction. PMID- 26666856 TI - Ten-year analysis of oral cancer focusing on young people in northern Thailand. AB - The objective of the present study was to assess the current situation of oral squamous cell carcinoma (OSCC) in northern Thailand, with an emphasis on patients <40 years of age. Medical records of patients histologically diagnosed with OSCC were collected from the Cancer Registry of Maharaj Nakorn Chiang Mai Hospital, Thailand between 2001 and 2010. The clinico-demographic data of patients aged <40 years (young group) and those aged >=40 years (old group) were compared. A total of 874 patients were included in this study, of which 4.1% were <40 years of age. The tongue was the most common cancer site in both age groups. Most patients in both age groups were diagnosed with oral cancer at stage IV. Tobacco smoking (62.3%) and alcohol consumption (52.3%) were the most common risk factors in both age groups. However, the rates of betel quid chewing (17.5%) had decreased from those found in our study in the previous decade (50.2%); these rates were not found in the young group. The 5-year survival rate was 27.4% for the old group and 56.2% for the young group. OSCC remains a serious oral health problem in northern Thailand, and it has not been resolved among young adults. PMID- 26666857 TI - Association of periodontal status with liver abnormalities and metabolic syndrome. AB - Although an association between periodontal status and liver abnormalities has been reported, it has not been described in relation to metabolic syndrome (MetS), which often coexists with non-alcoholic fatty liver disease. We examined the association of a combination of liver abnormality and MetS with periodontal condition in Japanese adults, based on the level of alcohol consumption. In 2008, 4,207 males aged 45.4 +/- 8.9 years and 1,270 females aged 45.9 +/- 9.7 years had annual workplace health check-ups at a company in Japan. Periodontal status was represented as periodontal pocket depth at the mesio-buccal and mid-buccal sites for all teeth. Alanine aminotransferase (ALT), and metabolic components were examined. Multiple linear regression analysis showed a significant association between deep pocket depth and the coexistence of elevated ALT and MetS in males with low alcohol consumption. Females showed no such relationship. In conclusion, the association between periodontal condition and the combination of elevated ALT and MetS was confirmed in males. That is, a clear association between liver abnormalities and periodontal condition was seen in male subjects with no or low alcohol consumption and MetS, providing new insights into the connection between liver function and periodontal health. PMID- 26666858 TI - Use of the Strength of Recommendation Taxonomy (SORT) to assess full-mouth treatments of chronic periodontitis. AB - Previous studies have not resolved whether scaling and root planing with a full mouth (with or without antiseptics) or quadrant approach is better for treatment of chronic periodontitis. We identified relevant studies and used Strength of Recommendation Taxonomy (SORT) criteria to critically interpret the results of all relevant studies. A literature search was performed using the PubMed, EMBASE, and Cochrane databases up to July 2015. Selected studies were stratified according to their quality, quantity, and consistency. In total, 377 studies were identified, and 36 articles selected for retrieval were stratified according SORT criteria, as follows: no level 1 studies, 15 level 2 studies, and 21 level 3 studies (which were excluded from subsequent analysis). Among the selected level 2 studies, including seven randomized clinical trials and three systematic reviews, 67% showed no significant difference between scaling and root planing with a full-mouth or quadrant approach. In conclusion, on the basis of the best available data, the strength of evidence is grade B (consistent, low-quality evidence) for full-mouth (with or without antiseptics) and quadrant scaling and root planing for treatment of chronic periodontitis. PMID- 26666859 TI - Characteristics of middle-aged and older patients with temporomandibular disorders and burning mouth syndrome. AB - The aim of this study was to evaluate the relationship between pain intensities and psychosocial characteristics in middle-aged and older patients with temporomandibular disorders (TMDs) and burning mouth syndrome (BMS). Subjects were selected according to the Research Diagnostic Criteria for TMD (n = 705) and International Association for the Study of Pain criteria for BMS (n = 175). Patients were then divided into two age groups: 45-64 years (middle-aged, Group A) and 65-84 years (older, Group B). Pain intensity and depression and somatization scores were evaluated in both groups. In BMS patients, present and worst pain intensities were significantly higher in Group B than in Group A {4.6 [95% confidence interval (CI) = 4.0-5.2] vs. 3.5 [95% CI = 3.1-3.9] and 5.9 [95% CI = 5.2-6.4] vs. 5.0 [95% CI = 4.5-5.6], respectively; P < 0.05}, with no difference observed in TMD patients. The depression and somatization scores were significantly higher in Group A than in Group B among BMS patients [0.57 (95% CI = 0.45-0.69) vs. 0.46 (95% CI = 0.34-0.59) and 0.537 (95% CI = 0.45-0.63) vs. 0.45 (95% CI = 0.34-0.55); P < 0.05], with no difference observed in TMD patients. The results of the present study indicate that pain intensities and psychosocial characteristics in BMS appear to differ between middle-aged and older patients. PMID- 26666860 TI - Micro-CT assessment of the sealing ability of three root canal filling techniques. AB - This study used micro-CT to compare three obturation techniques with respect to void occurrence in canals filled with bioceramic sealer. Thirty extracted first mandibular premolars were prepared with a ProTaper Universal system and randomly allocated to three groups. Canals were obturated with gutta-percha and bioceramic root canal sealer, using either single-cone, lateral compaction, or Thermafil filling technique. Each tooth was then scanned with micro-CT. Voids in 2D cross sectional images and void volumes in 3D images of all root thirds were assessed in relation to obturation technique. There was no significant difference between obturation techniques in the proportion of sections with voids (P > 0.05). However, the results of the obturation techniques significantly differed in relation to root region (P < 0.05). In conclusion, no root filling technique resulted in void-free specimens. Void volumes were highest for the single-cone technique and lowest for Thermafil, in all regions (P < 0.05). PMID- 26666861 TI - Effects of different antibacterial agents on enamel in a biofilm caries model. AB - Using a mature biofilm model, the aim of this study was to evaluate the effectiveness of different antibacterial agents in comparison with silver diamine fluoride (SDF). Forty-eight saliva-coated enamel slabs were inoculated with Streptococcus mutans monospecies biofilm. The biofilms were then exposed to 10% sucrose in tryptone yeast-extract culture medium, 8 times per day for 7 days. After the biofilm growth period, the enamel slabs were treated with one of the following substances: 1) distilled water; 2) SDF; 3) acidulated phosphate fluoride (APF); 4) ammonium hexafluorosilicate (AHF); 5) ammonium hexafluorosilicate + cetylpyridinium chloride (AHF+CPC); or 6) 0.2% chlorhexidine (CHX). After these treatment procedures, the samples were incubated at 37oC for 2 days, and the numbers of viable microorganisms in the biofilms were counted. The number of viable bacteria was significantly reduced by all of the antibacterial agents (P < 0.05). However, SDF showed the highest antibacterial activity (P < 0.05), and the effectiveness of the other agents was lower (P < 0.05). SDF has a highly effective antibacterial action against cariogenic Streptococcus mutans biofilm; none of the other fluoride agents used in this study, or 0.2 CHX agent, showed an antibacterial effect comparable to that of SDF. PMID- 26666862 TI - Comparative analysis of the gonial angle on lateral cephalometric radiographs and panoramic radiographs. AB - We measured the gonial angle (GA) on panoramic radiography (PR) and analyzed the correlation between the GA on PR and lateral cephalometric radiography (LCR). In total, 49 PR films and LCR films from dentate young adults were evaluated. Orthodontists plotted four points (articulare, menton, posterior gonion, and lower gonion) on the PR and carefully traced them. Using a protractor, two radiologists measured the GA on LCR images. A simultaneous experimental study of two dry skulls was performed to compare the GA on LCR and PR. The GA was slightly smaller on the PR of the dry mandible than on the LCR and tended to decrease continuously with magnitude toward the Frankfort horizontal plane. The mean GA was 115.1 +/- 5.2 degrees on PR and 122.2 +/- 6.4 degrees on the LCR. The values were highly correlated (Pearson product-moment correlation coefficient, 0.801). The GA on PR was nonsignificantly smaller than that measured on LCR. The difference may be due to head position, the inclination angle of the mandibular body, and/or the direction of the incident X-ray beam. PMID- 26666863 TI - Effect of brushing with two different abrasives on fluoride release by high viscosity glass ionomer cement. AB - The effect of brushing with two abrasive levels on the fluoride release of high viscosity glass ionomers (GIs) was investigated. Forty-eight GI discs were fabricated and randomly assigned to one of the four groups. Treatments, performed for 30 days, included exposure to a carboxymethylcellulose (CMC) solution without fluoride (CMC-F), CMC with 275 ppm fluoride (CMC+F), CMC with fluoride plus brushing with a low abrasive slurry (relative enamel abrasivity = 4; L-ab), and CMC with fluoride plus brushing with a high abrasive slurry (relative enamel abrasivity = 7; H-ab). Fluoride release was measured after 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 days. Surface analysis was performed using optical profilometry in addition to scanning electron microscopy. Data were compared using one-way analysis of variance (alpha = 0.05). Fluoride release was significantly different among groups, with group H-ab showing the highest rates. Cumulative fluoride release was 10% and 30% greater in groups L-ab and H-ab than in group CMC+F. High surface roughness values were associated with H-ab as well as greater exposure of silica fillers, as observed by scanning electron microscopy. Fluoride release from conventional GIs is enhanced by brushing with high abrasive slurries. PMID- 26666864 TI - Eleven-year clinical performance of a mandibular natural tooth pontic bonded with modified tri-n-butylborane initiated adhesive resin. AB - This clinical report describes the bonding procedure and clinical course of a natural tooth pontic in a 65-year-old male patient. A mandibular lateral incisor was extracted due to severe marginal periodontitis. The root of the tooth was amputated and a pontic structure was formed by filling acrylic resin into the coronal pulp chamber space. The enamel surface of the pontic and the adjacent abutment teeth were etched with phosphoric acid gel. The pontic was bonded with a modified tri-n-butylborane initiated adhesive resin (Super-Bond Quick). The connecters fractured 11 years after bonding when the patient accidentally bit a metallic chopstick. Recurrence of the fracture, however, did not occur, and the re-seated pontic has been functioning for more than 1 year. Although proper maintenance of both the periodontal tissue and splinted dentition is required, this minimally invasive technique can be applied in selected patients suffering from periodontal diseases. PMID- 26666865 TI - Osteochondroma of the coronoid process of the mandible. AB - We describe a rare case of osteochondroma of the coronoid process of mandible accompanied by severe trismus in a 14-year-old Japanese boy. The patient had initially been diagnosed as having internal derangement of the temporomandibular joint (TMJ), and conservative treatment had failed to improve the symptoms. Despite extremely limited TMJ movement, panoramic radiography revealed no abnormality, but magnetic resonance imaging suggested internal derangement of the left TMJ. Five months later, the trismus worsened and computed tomography revealed a bone-like mass confluent with the coronoid process, which was finally diagnosed as osteochondroma. The patient then underwent intra-oral coronoidectomy. PMID- 26666866 TI - Light-Up Probes Based on Fluorogens with Aggregation-Induced Emission Characteristics for Monoamine Oxidase-A Activity Study in Solution and in Living Cells. AB - Fluorogens with aggregation-induced emission (AIEgens) have emerged as a powerful and versatile platform for the development of novel biosensors. In this study, a series of water-soluble fluorescent probes based on tetraphenylethylene (TPE) were designed and synthesized for the detection of monoamine oxidases (MAOs) based on specific interactions between the probes and the proteins. Among the six probes developed, t-TPEM displays a significant fluorescence increase upon introduction of MAOs. Of particular significance is that the fluorescence of t TPEM in the presence of MAO-A is 21-fold higher than other proteins including MAO B. Lineweaver-Burk plots reveal that t-TPEM acts as an uncompetitive inhibitor of MAO-A with Ki = 17.1 MUM, which confirms its good binding affinity toward MAO-A. Furthermore, a cell imaging experiment reveals that t-TPEM is able to selectively monitor the activity of MAO-A which is localized in mitochondria of MCF-7 cells. PMID- 26666867 TI - Simultaneous determination of five quinoxaline-1,4-dioxides in animal feeds using an immunochromatographic strip. AB - An immunochromatographic (ICG) strip was developed for the simultaneous quantitative determination of five quinoxaline-1,4-dioxides in animal feed. For this purpose, polyclonal antibodies (PcAb) with group-specific quinoxaline-1,4 dioxides were conjugated to colloidal gold particles as the detection reagent for ICG strips to test for quinoxaline-1,4-dioxides. This method achieved semi quantitative detection of quinoxaline-1,4-dioxides within 5-10 min. The visual lower detection limits of the strip for quinocetone, cyadox, carbadox, mequindox and olaquindox were 10, 15, 15, 20 and 20 ng ml(-1), respectively. Using an ICG strip reader, the 50% inhibitions (IC50 values) were calculated to be 9.1, 13.5, 16.6, 20.2 and 21.3 ng ml(-1) for quinocetone, cyadox, carbadox, mequindox and olaquindox, respectively. When used to analyse samples of animal feed, acceptable recovery rates of 77.5-99.5% and coefficients of variation (CVs) of 4.3-10.7% were obtained. Levels measured with the ICG strip for 10 spiked samples were confirmed by HPLC with a high correlation coefficient of 0.9965 (n = 10). In conclusion, the method was rapid and accurate for simultaneous determination of five quinoxaline-1,4-dioxides antibiotics in animal feed. PMID- 26666868 TI - Wellbeing at work among kitchen workers during organic food conversion in Danish public kitchens: a longitudinal survey. AB - BACKGROUND: In 2011, the Danish Ministry of Food, Agriculture and Fisheries launched the Danish Organic Action Plan 2020 intending to double the organic agricultural area in Denmark. This study aims to measure experienced physical and psychological wellbeing at work along with beliefs and attitudes among kitchen workers before and after participating in educational training programmes in organic food conversion. METHOD: This longitudinal study applied an online self administered questionnaire among kitchen workers before and after the implementation of an organic food conversion programme with 1-year follow-up. The study targeted all staff members in the participating public kitchens taking part in the organic food conversion process funded by the Danish Organic Action Plan 2020. RESULTS: Of the 448 eligible kitchen workers, 235 completed the questionnaire at baseline (52%) and 149 at follow-up (63% of those surveyed at baseline). No substantive differences between baseline and follow-up measurements of organic food conversion were detected on physical or psychological wellbeing at work. Kitchen workers reported a significant improvement in the perceived food quality, motivation to work and application of nutritional guidelines. Reported organic food percentages for the kitchens also increased significantly (P< 0.001) and a shift from using ready-made food products to producing more food from base was indicated. CONCLUSION: Within 1 year, a significant increase in motivation to work among kitchen staff was observed with no substantive changes in physical or psychological wellbeing at work identified. The results support the Danish Organic Action Plan 2020 and initiatives of similar kind. PMID- 26666869 TI - Mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults (The ELSA and Bambui cohort ageing studies). AB - BACKGROUND: The main aim of this study was to quantify and compare 6-year mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults. This study represents a rare opportunity to approach the subject in two different social and economic contexts. METHODS: Data from the data from the English Longitudinal Study of Ageing (ELSA) and the Bambui Cohort Study of Ageing (Brazil) were used. Deaths in both cohorts were identified through mortality registers. Risk factors considered in this study were baseline smoking, hypertension and diabetes mellitus. Both age-sex adjusted hazard ratios and population attributable risks (PAR) of all-cause mortality and their 95% confidence intervals for the association between risk factors and mortality were estimated using Cox proportional hazards models. RESULTS: Participants were 3205 English and 1382 Brazilians aged 60 years and over. First, Brazilians showed much higher absolute risk of mortality than English and this finding was consistent in all age, independently of sex. Second, as a rule, hazard ratios for mortality to smoking, hypertension and diabetes showed more similarities than differences between these two populations. Third, there was strong difference among English and Brazilians on attributable deaths to hypertension. CONCLUSIONS: The findings indicate that, despite of being in more recent transitions, the attributable deaths to one or more risk factors was twofold among Brazilians relative to the English. These findings call attention for the challenge imposed to health systems to prevent and treat non-communicable diseases, particularly in populations with low socioeconomic level. PMID- 26666870 TI - Evaluation of WO2014207069 A1: Multitarget Hedgehog pathway inhibitors and uses thereof. AB - In recent years, the involvement of the Hedgehog (Hh) signaling pathway in various human diseases and dysfunctions has been clearly demonstrated. Smoothened (Smo), one of the upstream signal transducers, has been the most druggable target of the Hh pathway. However, the emergence of resistance to Smo inhibitors and the identification of Smo-independent activation of the Hh pathway led to the need to find new chemical entities able to interfere with downstream components, such as Gli. For this purpose, two different computational approaches have been applied to a small-sized library of natural compounds. As a result, an isoflavone derivative that showed ability to inhibit both Smo and Gli1 has been identified; namely, Glabrescione B. A new synthetic approach has been planned for this compound and its derivatives. Biological evaluation demonstrated the mechanism of action and showed a promising preclinical profile. PMID- 26666871 TI - Comparison of fecal pooling methods and DNA extraction kits for the detection of Mycobacterium avium subspecies paratuberculosis. AB - The aim of the study was to develop a sensitive method using quantitative real time polymerase chain reaction (qPCR) with pooled fecal samples for the screening of Johne's disease (JD). Manufacturer-specified and our new pooling method in combination with five commercial kits for DNA extraction and purification were compared. Different volumes of pooled fecal suspensions were tested, and the results were compared for individual samples and three pool sizes (5, 10, and 50 samples); each of the fecal suspensions, which were prepared from healthy dairy and beef cattle was spiked with 0, 10, 100, or 1000 cultured Mycobacterium avium subspecies paratuberculosis (MAP) organisms or was mixed with fecal suspensions from experimentally infected cattle. The MAP DNA detection proportion with our pooling method in combination with Johne-Spin kit (Fasmac, Japan) was 100% for all models and all pool sizes, except for the low shedder model with a pool size of 50. There was no loss of sensitivity in pools of 10 subjects or less by using the new method. These results suggest that new method is a sensitive, practical, and cost-effective screening test for the detection of MAP-infected cattle and the monitoring of JD-free herds. PMID- 26666872 TI - Unusual prenatal sonographic findings without an elevated maternal serum alpha fetoprotein level in a fetus with epidermolysis bullosa. AB - A 31-year-old pregnant woman was referred to us at 34.6 weeks' menstrual age for sonographic evaluation of a fetal left lower limb abnormality. Sonographic findings revealed shortening of the left tibia and dorsal hyperflexion of the left foot. There was no family history of genetic disease, and the maternal serum alpha-fetoprotein concentration was normal. A male infant was born with extensive skin peeling, mainly on his left leg, associated with muscular dystrophy. Epidermolysis bullosa was confirmed on a skin biopsy; the neonate died 53 days after birth as a result of severe sepsis. Although cutaneous epidermolysis bullosa is difficult to diagnose prenatally, shortening and deformity of extremities may provide a clue to the diagnosis, even when the maternal alpha fetoprotein concentration is normal. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:319-321, 2016. PMID- 26666873 TI - General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons. AB - Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies. PMID- 26666875 TI - Parallel assessment of Th17 cell frequencies by surface marker co-expression versus ex vivo IL-17 production in HIV-1 infection. AB - INTRODUCTION: Th17 cells can either be identified by co-staining of surface markers or by intracellular cytokine staining (ICS) for IL-17 production. Discrepancies regarding the published frequencies of Th17 cells in peripheral blood mononuclear cells (PBMC) of HIV patients may partly be due to the different methodologies used. METHODS: Cryopreserved PBMC from healthy controls and HIV infected subjects, including treated (cART) and viremic patients, were split and analyzed side-by-side by flow cytometry for expression of surface markers CCR6, CXCR3, CCR4, and CD161, or for intracellular expression of IL-17A and IFNgamma after stimulation. RESULTS: The characterization of Th17 cells as CXCR3 - CCR6 + CCR4 + CD161+ yielded considerably higher frequencies than the corresponding frequencies obtained by characterization via cytokines (IL-17 + IFNgamma-), regardless of the HIV status. However, the overall frequencies delivered by the two methods significantly correlated. The relative frequency of Th17 cells within the CD4+ T cell compartment was preserved in HIV infection but there was a significant decrease in the absolute Th17 number, which was restored after initiation of cART, paralleling CD4+ T cell recovery. Absolute Th17 numbers inversely correlated with HIV viral load. CONCLUSION: The definition of Th17 cells by surface markers might overestimate their frequency in comparison to functional assessment of IL-17 production by ICS, regardless of the HIV infection status. However, both methods yield proportionate results with reduced absolute numbers of Th17 cells in untreated HIV disease, reflecting the depletion of total CD4+ T cells in viremic HIV patients, and restoration with cART. (c) 2016 International Clinical Cytometry Society. PMID- 26666876 TI - Atorvastatin May Correct Dyslipidemia in Adult Patients at Risk for Alzheimer's Disease Through an Anti-Inflammatory Pathway. AB - BACKGROUND: Dyslipidemia is a risk factor for the pathogenesis of Alzheimer's disease. Although, atorvastatin is a well-accepted lipid-lowering agent, the benefits of atorvastatin treatment through an anti-inflammatory mechanism are still unclear. OBJECTIVE: The present study was designed to examine changes in inflammatory markers following administration of atorvastatin in dyslipidemic patients with a parental history of Alzheimer's disease. METHODS: Dyslipidemic adults with a parental history of Alzheimer's disease were administered either 40 mg of atorvastatin or placebo for 18 months. Before and after the study, lpid levels, blood pressure, body weight and body mass index, and the inflammatory markers hs-Creactive protein, serum monocyte chemoattractant protien-1, interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were tested. RESULTS: Baseline levels of lipids, body mass index, hs-Creactive protein, monocyte chemoattractant protien-1, interleukin- 1beta, interleukin-6 and tumor necrosis factor-alpha did not show any difference between the two groups. However, after 18 months of atorvastatin treatment, all inflammatory markers significantly decreased in association with a reduction of lipid profiles, body mass index, bodyweight, and blood pressure, compared with those patients treated with placebo. CONCLUSION: Administration of atorvastatin corrected dyslipidemia in association with a reduction in inflammatory markers. Our results suggest that the therapeutic benefits of atorvastatin possibly involve an anti-inflammatory pathway. PMID- 26666877 TI - Building an Australasian paramedicine research agenda: a narrative review. AB - The need for paramedicine research has been recognised internationally through efforts to develop out-of-hospital research agendas in several developed countries. Australasia has a substantial paramedicine research capacity compared to the discipline internationally and is well positioned as a potential leader in the drive towards evidence-based policy and practice in paramedicine. Our objective was to draw on international experiences to identify and recommend the best methodological approach that should be employed to develop an Australasian paramedicine research agenda. A search and critical appraisal process was employed to produce an overview of the literature related to the development of paramedicine research agendas throughout the world. Based on these international experiences, and our own analysis of the Australasian context, we recommend that a mixed methods approach be used to develop an inclusive Australasian Paramedicine Research Agenda. This approach will capture the views and interests of a wide range of expert stakeholders through multiple data collection strategies, including interviews, roundtable discussions and an online Delphi consensus survey. Paramedic researchers and industry leaders have the opportunity to use this multidisciplinary process of inquiry to develop a paramedicine research agenda that will provide a framework for the development of a culture of open evaluation, innovation and improvement. This research agenda would assess the progress of paramedicine research in Australia and New Zealand, map the research capacity of the paramedicine discipline, paramedic services, universities and professional organisations, identify current strengths and opportunities, make recommendations to capitalize on opportunities, and identify research priorities. Success will depend on ensuring the participation of a representative sample of expert stakeholders, fostering an open and collaborative roundtable discussion, and adhering to a predefined approach to measure consensus on each topic. PMID- 26666879 TI - Leucocyte Telomere Length and Risk of Cardiovascular Disease in a Cohort of 1,397 Danish Men and Women. AB - OBJECTIVES: Short leucocyte telomere length (LTL) might be a risk factor for cardiovascular diseases (CVD). The present study examines the relation between LTL and incident fatal or non-fatal CVD, ischaemic heart disease (IHD) and stroke in a Danish cohort followed for 29 years. METHODS: In total, 1,397 men and women who participated in health examinations with blood sampling in 1981-1984 were followed for CVD outcomes until the end of 2012 by linkage to national registers. Cox proportional hazard regression models were used to analyse the relation between LTL and CVD adjusting for potential confounding CVD risk factors. RESULTS: During the follow-up, 603 participants experienced an incident fatal or non-fatal CVD. The survival analysis showed that baseline LTL was not associated with CVD outcomes. In the subanalysis with IHD as outcome, those with middle and short LTL had an increased hazard rate ratio of 1.97 (95% CI 1.31-2.93) and 1.55 (95% CI 1.02-2.35), respectively, which was attenuated when confounding factors were adjusted for. For stroke, the pattern of associations was similar but less precisely estimated. CONCLUSIONS: In this study short, LTL was not associated with an increased risk of CVD, but modestly associated with an increased risk of IHD. PMID- 26666878 TI - Optic glioma and precocious puberty in a girl with neurofibromatosis type 1 carrying an R681X mutation of NF1: case report and review of the literature. AB - BACKGROUND: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with an extremely variable phenotype. In childhood NF1 can be associated with optic glioma and central precocious puberty; the latter is more common when the optic chiasm is affected. The mutational spectrum of the NF1 gene is wide and complex; R681X is a rare severe mutation of the NF1 gene known to cause truncation of neurofibromin, with only ten reported cases in the literature so far. CASE PRESENTATION: We describe a girl with NF1 associated with early central precocious puberty appearing at 2.5 years of age and optic glioma affecting the optic chiasm as seen on magnetic resonance imaging (MRI). Genetic analysis confirmed the presence of R681X. Therapy with a gonadotropin-releasing hormone agonist was instituted with good response to therapy. The lesions on MRI were stable and no significant vision impairment was present during the 6 years of follow-up. CONCLUSION: Of the ten reported cases of NF1 due to R681X, one has presented with optic glioma and none with precocious puberty. Thus, to our knowledge, this is the first reported case of this mutation presenting with precocious puberty. We believe that this is a contribution to the few reports on the phenotype of this mutation and to the future elucidation of genotype phenotype correlations of this disease. PMID- 26666880 TI - Prognostic prediction of male recipients selected for liver transplantation: With special attention to neutrophil to lymphocyte ratio. AB - AIM: Neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker that has a close relationship with tumor progression and metastasis. In this study, we aimed to investigate the role of NLR in the prognosis of male candidates with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). METHODS: We analyzed the clinical data of 248 male HCC candidates who underwent LT in our Liver Transplantation Center between 2002 and 2012. All risk factors were analyzed by univariate and multivariate Cox analysis and survival rates were calculated by Kaplan-Meier log-rank test. RESULTS: NLR was proved to be an independent risk factor affecting overall survival (OS) (P < 0.001) and tumor free survival (TFS) (P = 0.003) of male candidates with HCC following LT. Additionally, our study showed that elevated NLR (>4) was associated with early tumor recurrence by Kaplan-Meier analysis. Furthermore, we established Model_OS and Model_TFS to predict prognosis based on multivariate Cox analysis. Our study showed that male candidates with HCC who exceeded the Milan criteria but within Model_OS could achieve similar OS as those within the Milan criteria (P = 0.220). Similarly, male patients who exceeded the Milan criteria but within Model_TFS could achieve similar TFS as those within the Milan criteria (P = 0.197). CONCLUSION: Proper inflammatory response may effectively reduce tumor recurrence after LT. Elevated NLR (>4) within a certain range is associated with early tumor recurrence. NLR-based models are efficient and safe for prognostic prediction among male candidates with HCC for LT. PMID- 26666881 TI - Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? AB - Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF).Novel compounds have to be identified and tailored in combination to specific CFTR mutations, to different tissues, or even to the individual patient. Immortalized cell lines overexpressing mutant CFTR are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of CFTR maturation and turnover requires the use of cellular models that closely recapitulate the specific properties of the clinically most affected organs. Importantly, current screening efforts based on primary airway cells or intestinal organoids cannot specifically target single rare CFTR mutations or mimic multiple cell types.In the near future, genetically engineered induced pluripotent stem cells will provide an excellent basis for personalized organotypic models of CF disease and biological screens for identification of CFTR potentiators and correctors. PMID- 26666882 TI - Coronary artery bypass grafting in Takayasu's disease--importance of the proximal anastomosis: a case report. AB - INTRODUCTION: Treatment of coronary artery involvement in Takayasu's arteritis is challenging. Coronary artery bypass grafting may be required. The use of saphenous vein grafts is recommended because of possible inflammatory involvement of the internal thoracic arteries. However, inserting the proximal anastomosis on inflamed aortic tissue may give rise to stenosis. Only a few cases of inserting a proximal anastomosis in patients with Takayasu's arteritis have been reported in the literature. To date, no consensus has been reached on the best way to perform this procedure in patients with Takayasu's arteritis. CASE PRESENTATION: We report a case of a 25-year-old white woman with Takayasu's arteritis who had recurrent angina after two previous treatments had failed, due to left main stem stenosis. She was successfully treated by coronary artery bypass grafting using a Dacron patch to insert the proximal anastomosis. CONCLUSIONS: We are the first to report an uncomplicated case in which a Dacron (Vascutek(r), Renfrewshire) prosthetic patch was used to insert the proximal anastomosis on an inflamed aorta in a patient with Takayasu's arteritis. The patch prevents contact between inflamed tissue and the graft, which we believe reduces the risk of graft failure. This case might inspire other thoracic surgeons in the challenging task of performing revascularization techniques in patients with an inflamed and fragile aorta. PMID- 26666883 TI - An Exploratory Study of a New Kink Activity: "Pup Play". AB - This study presents the narratives and experiences of 30 gay and bisexual men who participate in a behavior known as "pup play." Never empirically studied before, we use in-depth interviews and a modified form of grounded theory to describe the dynamics of pup play and develop a conceptual framework with which to understand it. We discuss the dynamics of pup play, demonstrating that it primarily consists of mimicking the behaviors and adopting the role of a dog. We show that the majority of participants use pup play for sexual satisfaction. It is also a form of relaxation, demonstrated primarily through the existence of a "headspace." We classify pup play as a kink, and find no evidence for the framing of it as a form of zoophilia. We call for further research on pup play as a sexual kink and leisure activity from both qualitative and quantitative perspectives. PMID- 26666885 TI - Effect of plasma nitriding treatment on structural, tribological and electrochemical properties of commercially pure titanium. AB - In this study, plasma nitriding treatment was applied to commercially pure titanium (Grade 2). Structural properties, electrochemical and tribological behaviours of the nitrided pure titanium specimens were comparatively investigated. Microstructure and morphology of the plasma nitrided specimens were analysed by X-ray diffraction and scanning electron microscopy. Furthermore, corrosion tests were conducted in Ringer's solution, which represents a human body environment, to determine electrochemical properties. Then, tribological and frictional properties were investigated using pin-on-disc tribometer, and a micro hardness tester was used to measure the hardness of the coatings. The results showed that plasma nitrided specimens exhibited higher surface hardness than the untreated specimens did. In addition, the plasma nitrided specimens at 700 degrees C presented significantly better performance than the other plasma nitrided specimens (at 500 degrees C and 600 degrees C) under dry wear conditions. Moreover, corrosion test results showed that corrosion behaviours of untreated and nitrided samples had similar characteristic. PMID- 26666884 TI - Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers. AB - Tubulointerstitial nephritis (TIN) is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4 positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4 positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjogren syndrome, or anti-neutrophil cytoplasmic antibody associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described. PMID- 26666886 TI - The complete mitochondrial genome of the dwarf tapeworm Hymenolepis nana--a neglected zoonotic helminth. AB - Hymenolepis nana, commonly known as the dwarf tapeworm, is one of the most common tapeworms of humans and rodents and can cause hymenolepiasis. Although this zoonotic tapeworm is of socio-economic significance in many countries of the world, its genetics, systematics, epidemiology, and biology are poorly understood. In the present study, we sequenced and characterized the complete mitochondrial (mt) genome of H. nana. The mt genome is 13,764 bp in size and encodes 36 genes, including 12 protein-coding genes, 2 ribosomal RNA, and 22 transfer RNA genes. All genes are transcribed in the same direction. The gene order and genome content are completely identical with their congener Hymenolepis diminuta. Phylogenetic analyses based on concatenated amino acid sequences of 12 protein-coding genes by Bayesian inference, Maximum likelihood, and Maximum parsimony showed the division of class Cestoda into two orders, supported the monophylies of both the orders Cyclophyllidea and Pseudophyllidea. Analyses of mt genome sequences also support the monophylies of the three families Taeniidae, Hymenolepididae, and Diphyllobothriidae. This novel mt genome provides a useful genetic marker for studying the molecular epidemiology, systematics, and population genetics of the dwarf tapeworm and should have implications for the diagnosis, prevention, and control of hymenolepiasis in humans. PMID- 26666887 TI - Ecological factors responsible for the geographic distribution of Rhabdias joaquinensis: where do lungworms infect anurans in nature? AB - The lungworm Rhabdias joaquinensis (Nematoda: Rhabdiasidae) is a common parasite of anurans in eastern Nebraska, yet absent from the same hosts in western Nebraska. This study investigated the ecology of the lungworm's free-living stages that reside in host feces and surrounding soils to establish the worm's free-living niche in eastern Nebraska. Using a comparative method, this study also investigated the absence of lungworms in western Nebraska's Sandhills. Soil composition, moisture, and temperature were experimentally varied in the laboratory to assess their effects on juvenile development and survival. Field mesocosm and host defecation experiments were used to determine where in nature lungworms survive and eventually infect frogs and toads and to discover if vegetation facilitates lungworm transmission to hosts. The results found loam soils were amenable to lungworm development, whereas soils with high clay or sand content produced few infective lungworms. Soil moisture <50 % did not support lungworm development. Infective juveniles successfully developed between 5 and 35 degrees C, albeit at different rates, whereas only a limited number of non infective worms developed at 40 degrees C. Field studies found that shoreline environments supported lungworm development, and the majority of lungworm infections appear to occur within a zone of infection adjacent to shorelines in eastern Nebraska. The prevalence in vegetation mesocosms was 100 %, and a significantly higher mean abundance was found in toads from containers with vegetation than without. Overall, these experiments suggest that the spatial distribution of R. joaquinensis in Nebraska is constrained by the worm's ability to survive and reproduce in a soil matrix. PMID- 26666888 TI - [Memantine for optic nerve atrophy in Friedreich's Ataxia]. AB - A 24-year-old patient with Friedreich's ataxia presented with advanced visual loss due to optic nerve atrophy. After interdisciplinary consultation and after obtaining informed consent, an off-label therapy with the N-methyl-D-aspartate (NMDA) antagonist memantine was initiated. In a 1-year follow-up no further loss of the nerve fiber layer could be detected by optical coherence tomography (OCT) and visual acuity remained stable. Despite the limitations of this single and time limited case observational study, memantine should be discussed as an option for treatment of acute optic nerve atrophy in Friedreich's ataxia. PMID- 26666890 TI - Acrylamide mitigation strategies: critical appraisal of the FoodDrinkEurope toolbox. AB - FoodDrinkEurope Federation recently released the latest version of the Acrylamide Toolbox to support manufacturers in acrylamide reduction activities giving indication about the possible mitigation strategies. The Toolbox is intended for small and medium size enterprises with limited R&D resources, however no comments about the pro and cons of the different measures were provided to advise the potential users. Experts of the field are aware that not all the strategies proposed have equal value in terms of efficacy and cost/benefit ratio. This consideration prompted us to provide a qualitative science-based ranking of the mitigation strategies proposed in the acrylamide Toolbox, focusing on bakery and fried potato products. Five authors from different geographical areas having a publication record on acrylamide mitigation strategies worked independently ranking the efficacy of the acrylamide mitigation strategies taking into account three key parameters: (i) reduction rate; (ii) side effects; and (iii) applicability and economic impact. On the basis of their own experience and considering selected literature of the last ten years, the authors scored for each key parameter the acrylamide mitigation strategies proposed in the Toolbox. As expected, all strategies selected in the Toolbox turned out to be useful, however, not at the same level. The use of enzyme asparaginase and the selection of low sugar varieties were considered the best mitigation strategies in bakery and in potato products, respectively. According to authors' opinion most of the other mitigation strategies, although effective, either have relevant side effects on the sensory profile of the products, or they are not easy to implement in industrial production. The final outcome was a science based commented ranking which can enrich the acrylamide Toolbox supporting individual manufacturer in taking the best actions to reduce the acrylamide content in their specific production context. PMID- 26666889 TI - Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates. AB - BACKGROUND: Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. RESULTS: An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. CONCLUSION: These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting. PMID- 26666891 TI - Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy. AB - Individuals affected by restrictive cardiomyopathy (RCM) often develop heart failure at young ages resulting in early heart transplantation. Familial forms are mainly caused by mutations in sarcomere proteins and demonstrate a common genetic etiology with other inherited cardiomyopathies. Using next-generation sequencing, we identified two novel missense variants (p.S1624L; p.I2160F) in filamin-C (FLNC), an actin-cross-linking protein mainly expressed in heart and skeletal muscle, segregating in two families with autosomal-dominant RCM. Affected individuals presented with heart failure due to severe diastolic dysfunction requiring heart transplantation in some cases. Histopathology of heart tissue from patients of both families showed cytoplasmic inclusions suggesting protein aggregates, which were filamin-C specific for the p.S1624L by immunohistochemistry. Cytoplasmic aggregates were also observed in transfected myoblast cell lines expressing this mutant filamin-C indicating further evidence for its pathogenicity. Thus, FLNC is a disease gene for autosomal-dominant RCM and broadens the phenotype spectrum of filaminopathies. PMID- 26666892 TI - Phenotypic classification of variability of non-syndromic congenital cleft lip and jaw in Vorderwald * Montbeliarde cattle. AB - BACKGROUND: Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in several cattle breeds, but a detailed classification system does not exist for cattle. The objective of the present study was to describe the phenotypic variability of this orofacial malformation in Vorderwald * Montbeliarde cattle. For this purpose, a classification system of CLJ was developed on examination of five orofacial structures: (1) lips, (2) the processus (proc.) nasalis of the os incisivum, (3) the dental plate with adjacent segments of the hard palate, (4) the facial bones (os incisivum, os maxillare, os nasale and os palatinum) and (5) the mandibles. Each structure was given a score reflecting the degree of the lesion from absent (score 0) to severe. RESULTS: Nine cases were included in the study and they shared absence of the abaxial rostral part of the processus (proc.) nasalis of the os incisivum, partial loss of the rugae palatinae and the dental plate. A sigmoid curvature of the rostral lower jaw as well as a lateral deviation of the face and rostral lower jaw was highly variable in their expression. These deformations were present in eight of nine cases. In addition to the complete CLJ, three animals had an incomplete CLJ on the contralateral site with variable defects of the rostral part of the proc. nasalis of the os incisivum. CONCLUSIONS: A complete CLJ is obviously accompanied by a loss of parts of the proc. nasalis of the os incisivum. Extent and localization of the missing parts of the proc. nasalis were similar in all cases. A precise classification of the various CLJ forms is necessary. PMID- 26666894 TI - Do heads of government age more quickly? Observational study comparing mortality between elected leaders and runners-up in national elections of 17 countries. AB - OBJECTIVES: To determine whether being elected to head of government is associated with accelerated mortality by studying survival differences between people elected to office and unelected runner-up candidates who never served. DESIGN: Observational study. SETTING: Historical survival data on elected and runner-up candidates in parliamentary or presidential elections in Australia, Austria, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Italy, New Zealand, Norway, Poland, Spain, Sweden, United Kingdom, and United States, from 1722 to 2015. PARTICIPANTS: Elected and runner-up political candidates. MAIN OUTCOME MEASURE: Observed number of years alive after each candidate's last election, relative to what would be expected for an average person of the same age and sex as the candidate during the year of the election, based on historical French and British life tables. Observed post-election life years were compared between elected candidates and runners-up, adjusting for life expectancy at time of election. A Cox proportional hazards model (adjusted for candidate's life expectancy at the time of election) considered years until death (or years until end of study period for those not yet deceased by 9 September 2015) for elected candidates versus runners-up. RESULTS: The sample included 540 candidates: 279 winners and 261 runners-up who never served. A total of 380 candidates were deceased by 9 September 2015. Candidates who served as a head of government lived 4.4 (95% confidence interval 2.1 to 6.6) fewer years after their last election than did candidates who never served (17.8 v 13.4 years after last election; adjusted difference 2.7 (0.6 to 4.8) years). In Cox proportional hazards analysis, which considered all candidates (alive or deceased), the mortality hazard for elected candidates relative to runners-up was 1.23 (1.00 to 1.52). CONCLUSIONS: Election to head of government is associated with a substantial increase in mortality risk compared with candidates in national elections who never served. PMID- 26666895 TI - Association of Socioeconomic Status with Eye Health Among Women With and Without Diabetes. AB - OBJECTIVE: To investigate the association between socioeconomic position (SEP) and poor eye health among women. MATERIALS AND METHODS: We included the 7,708 women aged >= 40 years who participated in the 2008 National Health Interview Survey. We defined poor eye health as self-reported age-related eye diseases (AREDs; cataract, glaucoma, macular degeneration, or diabetic retinopathy) or visual impairment (VI). We identified diagnosed diabetes by self-report. We measured SEP by education attained and annual household income. We conducted logistic regression analyses while controlling for demographic, clinical, behavioral, and healthcare access variables. RESULTS: The age-standardized prevalence of VI and ARED was significantly higher among women with diagnosed diabetes than among those without diagnosed diabetes, 29.8% versus 14.4% and 34.1% versus 20.8%, respectively (p < 0.05 for both). The prevalence of VI and ARED increased with decreasing SEP, but the trends were only significant among women without diabetes. After multivariable adjustment, education and income were significantly associated with VI but not with ARED. We found no interaction with diagnosed diabetes. CONCLUSIONS: SEP was inversely associated with VI but not with ARED. We found no interaction with diagnosed diabetes. PMID- 26666897 TI - Visual motion transforms visual space representations similarly throughout the human visual hierarchy. AB - Several studies demonstrate that visual stimulus motion affects neural receptive fields and fMRI response amplitudes. Here we unite results of these two approaches and extend them by examining the effects of visual motion on neural position preferences throughout the hierarchy of human visual field maps. We measured population receptive field (pRF) properties using high-field fMRI (7T), characterizing position preferences simultaneously over large regions of the visual cortex. We measured pRFs properties using sine wave gratings in stationary apertures, moving at various speeds in either the direction of pRF measurement or the orthogonal direction. We find direction- and speed-dependent changes in pRF preferred position and size in all visual field maps examined, including V1, V3A, and the MT+ map TO1. These effects on pRF properties increase up the hierarchy of visual field maps. However, both within and between visual field maps the extent of pRF changes was approximately proportional to pRF size. This suggests that visual motion transforms the representation of visual space similarly throughout the visual hierarchy. Visual motion can also produce an illusory displacement of perceived stimulus position. We demonstrate perceptual displacements using the same stimulus configuration. In contrast to effects on pRF properties, perceptual displacements show only weak effects of motion speed, with far larger speed independent effects. We describe a model where low-level mechanisms could underlie the observed effects on neural position preferences. We conclude that visual motion induces similar transformations of visuo-spatial representations throughout the visual hierarchy, which may arise through low-level mechanisms. PMID- 26666898 TI - Magnetic vestibular stimulation modulates default mode network fluctuations. AB - Strong magnetic fields (>1 Tesla) can cause dizziness and it was recently shown that healthy subjects (resting in total darkness) developed a persistent nystagmus even when remaining completely motionless within a MR tomograph. Consequently, it was speculated that this magnetic vestibular stimulation (MVS) might influence fMRI results, as nystagmus is indicative of an imbalance in the vestibular system, potentially influencing other systems via multisensory vestibular interactions. The objective of our study was to investigate whether MVS does indeed modulate BOLD signal fluctuations. We recorded eye movements, as well as, resting-state fMRI of 30 volunteers in darkness at 1.5 T and 3.0 T to answer the question whether MVS modulated parts of the default mode resting-state network (DMN) in accordance with the Lorentz-force model for MVS, while distinguishing this from the known signal increase due to field strength related imaging effects. Our results showed that modulation of the default mode network occurred mainly in areas associated with vestibular and ocular motor function, and was in accordance with the Lorentz-force model, i.e., double than the expected signal scaling due to field strength alone. We discuss the implications of our findings for the interpretation of studies using resting-state fMRI, especially those concerning vestibular research. We conclude that MVS needs to be considered in vestibular research to avoid biased results, but it might also offer the possibility of manipulating network dynamics and may thus help in studying the brain as a dynamical system. PMID- 26666896 TI - Syntactic processing is distributed across the language system. AB - Language comprehension recruits an extended set of regions in the human brain. Is syntactic processing localized to a particular region or regions within this system, or is it distributed across the entire ensemble of brain regions that support high-level linguistic processing? Evidence from aphasic patients is more consistent with the latter possibility: damage to many different language regions and to white-matter tracts connecting them has been shown to lead to similar syntactic comprehension deficits. However, brain imaging investigations of syntactic processing continue to focus on particular regions within the language system, often parts of Broca's area and regions in the posterior temporal cortex. We hypothesized that, whereas the entire language system is in fact sensitive to syntactic complexity, the effects in some regions may be difficult to detect because of the overall lower response to language stimuli. Using an individual subjects approach to localizing the language system, shown in prior work to be more sensitive than traditional group analyses, we indeed find responses to syntactic complexity throughout this system, consistent with the findings from the neuropsychological patient literature. We speculate that such distributed nature of syntactic processing could perhaps imply that syntax is inseparable from other aspects of language comprehension (e.g., lexico-semantic processing), in line with current linguistic and psycholinguistic theories and evidence. Neuroimaging investigations of syntactic processing thus need to expand their scope to include the entire system of high-level language processing regions in order to fully understand how syntax is instantiated in the human brain. PMID- 26666899 TI - Contingent negative variation (CNV) associated with sensorimotor timing error correction. AB - INTRODUCTION: Detection and subsequent correction of sensorimotor timing errors are fundamental to adaptive behavior. Using scalp-recorded event-related potentials (ERPs), we sought to find ERP components that are predictive of error correction performance during rhythmic movements. METHOD: Healthy right-handed participants were asked to synchronize their finger taps to a regular tone sequence (every 600 ms), while EEG data were continuously recorded. Data from 15 participants were analyzed. Occasional irregularities were built into stimulus presentation timing: 90 ms before (advances: negative shift) or after (delays: positive shift) the expected time point. A tapping condition alternated with a listening condition in which identical stimulus sequence was presented but participants did not tap. RESULTS: Behavioral error correction was observed immediately following a shift, with a degree of over-correction with positive shifts. Our stimulus-locked ERP data analysis revealed, 1) increased auditory N1 amplitude for the positive shift condition and decreased auditory N1 modulation for the negative shift condition; and 2) a second enhanced negativity (N2) in the tapping positive condition, compared with the tapping negative condition. In response-locked epochs, we observed a CNV (contingent negative variation)-like negativity with earlier latency in the tapping negative condition compared with the tapping positive condition. This CNV-like negativity peaked at around the onset of subsequent tapping, with the earlier the peak, the better the error correction performance with the negative shifts while the later the peak, the better the error correction performance with the positive shifts. DISCUSSION: This study showed that the CNV-like negativity was associated with the error correction performance during our sensorimotor synchronization study. Auditory N1 and N2 were differentially involved in negative vs. positive error correction. However, we did not find evidence for their involvement in behavioral error correction. Overall, our study provides the basis from which further research on the role of the CNV in perceptual and motor timing can be developed. PMID- 26666900 TI - Radial bias is not necessary for orientation decoding. AB - Multivariate pattern analysis can be used to decode the orientation of a viewed grating from fMRI signals in early visual areas. Although some studies have reported identifying multiple sources of the orientation information that make decoding possible, a recent study argued that orientation decoding is only possible because of a single source: a coarse-scale retinotopically organized preference for radial orientations. Here we aim to resolve these discrepant findings. We show that there were subtle, but critical, experimental design choices that led to the erroneous conclusion that a radial bias is the only source of orientation information in fMRI signals. In particular, we show that the reliance on a fast temporal-encoding paradigm for spatial mapping can be problematic, as effects of space and time become conflated and lead to distorted estimates of a voxel's orientation or retinotopic preference. When we implement minor changes to the temporal paradigm or to the visual stimulus itself, by slowing the periodic rotation of the stimulus or by smoothing its contrast-energy profile, we find significant evidence of orientation information that does not originate from radial bias. In an additional block-paradigm experiment where space and time were not conflated, we apply a formal model comparison approach and find that many voxels exhibit more complex tuning properties than predicted by radial bias alone or in combination with other known coarse-scale biases. Our findings support the conclusion that radial bias is not necessary for orientation decoding. In addition, our study highlights potential limitations of using temporal phase-encoded fMRI designs for characterizing voxel tuning properties. PMID- 26666901 TI - One-pot preparation of labelled mannan-peptide conjugate, model for immune cell processing. AB - An efficient method for preparation of fluorescently labelled mannan-peptide glycoconjugates has been developed. After selective Dess-Martin periodinane oxidation of mannan, it was conjugated to the fluorescent label alone and a peptide with the label via reductive amination. Prepared glycoconjugates were characterised by HPSEC, FTIR-ATR and UV-VIS spectroscopy. Finally, the fluorescently labelled mannan and mannan-peptide conjugate were used for microscopic visualization of their accumulation in intracellular organelles of RAW 264.7 cells. PMID- 26666902 TI - Arterial Compliance Measurement in Overweight and Hypertensive Children. AB - OBJECTIVES: To investigate the pulse wave velocity (PWV) and augmentation index (Alx), measures of arterial stiffness, in relation to hypertension and obesity, the main risk factors for cardiovascular diseases. METHODS: Two groups of pediatric patients, 31 children and adolescents with hypertension and 85 with overweight, were analysed and compared to the control group (50 healthy individuals). Subjects were sampled by opportunity sampling at the Department of Pediatrics, Maribor. In each patient, blood pressure, anthropometrical parameters and PWV measurements using the applanation tonometry technique were performed. RESULTS: There was a significant correlation between PWV and age (r = 0.461, p = 0.001) in the control group, whereas no correlation was obtained between PWV and body mass index (BMI) or central mean arterial pressure (CMAP). In the hypertensive group, PWV only correlated with CMAP (r = 0.496, p = 0.005). A significant correlation was found in the overweight group between PWV and both age and BMI (r = 0.484, p < 0.001 and r = 0.347, p = 0.001, respectively). Alx results were not taken into consideration. CONCLUSIONS: The results of this pilot study show that overweight and hypertensive children and adolescents are associated with less compliant arteries than their healthy peers, which could be used for screening of patients with expected early cardiovascular risk. PMID- 26666903 TI - Wide-field Digital Ophthalmic Imaging in Infants using Nasal Endoscopic System. AB - OBJECTIVE: To report the utility of nasal endoscopic system in viewing the iridocorneal angle and fundus using various nasal endoscopes and light sources and to determine which type suits best to image a given location in the eye. METHODS: This is a prospective observational study of 20 eyes of 10 consecutive infants, who were scheduled for irrigation and probing for congenital nasolacrimal duct obstruction under general anesthesia. The pupils were dilated, viscoelastic gel was applied on the cornea and imaging was performed using nasal endoscopes. The endoscopes used were of 2.7 mm and 4 mm diameter, each with various angulations of 0(0), 30(0) and 70(0). Two different cold light illuminators (Xenon and Halogen) were used uniformly in all cases. Images were analyzed for their quality, clarity and extent of the fields captured. RESULTS: In all the 20 eyes, nasal endoscope provided a clear circular view of the iridocorneal angle and wide-field fundus view in a single glimpse. The 4 mm endoscope offered a wider view while in-air disc analysis was better with the 2.7 mm endoscope. Angulated endoscopes were more useful in imaging the iridocorneal angle, peripheral retina up to the ora serrata and ciliary body. The image quality with the xenon and halogen light sources were found to be comparable. The time taken for a single eye examination did not exceed 5 min. CONCLUSIONS: With good techniques and appropriate selection of nasal endoscopes, viewing of the iridocorneal angle and fundus is easy, possibly less expensive and very useful in infants. PMID- 26666904 TI - Early House Dust Mite Sensitivity in Mumbai Children. AB - OBJECTIVE: To identify house dust mite (HDM) sensitivity by skin prick test in children with allergic rhinitis, allergic wheezing and eczema. METHODS: In this prospective study, children with persistent or recurrent allergic symptoms of rhinitis, wheezing and eczema were enrolled to undergo skin prick testing. Sensitivity was checked for three mites: Dermatophagoide farinae, Dermatophagoide pteronyssinus, and Blomia tropicalis. RESULTS: Total 92 children underwent skin prick test; 49 (53.2 %) showed significant positivity to one or more dust mite. In the HDM sensitized group, a positive family history of allergic disorders was present in 32 children (65.3 %). In the HDM sensitized group, 18 (36.7 %) children had allergic rhinitis. The youngest child in this group was 12-mo-old. Ten (55.55 %) children were less than 24 mo of age. Significant sensitization to mites was detected in 7 (14.28 %) children with eczema. All children were below 24 mo of age. In children with a tendency to wheeze frequently without any evidence of infections or other systemic disease, 24 (48.9 %) had sensitization to HDM. The youngest child was 15 mo of age. Ten (41.6 %) children were below 24 mo of age. Sensitivity to Blomia tropicalis was detected in 6 (12.24 %) children. Significantly more number of children were sensitive to D. pteronyssinus as compared to D. farinae (65.31 % vs. 46.94 %; p = 0.034). CONCLUSIONS: Children in Mumbai show early sensitization to HDM. D. pteronyssinus is the commonest offending allergen in the index study. PMID- 26666905 TI - Discrimination in Seeking Medical Care for Female Child from Birth to Adolescence -A Retrospective Study. AB - OBJECTIVE: To study the bias in seeking medical care for female child in various age groups from birth to adolescence. METHODS: It is a retrospective analysis of the hospital records for the period January 2010 through December 2012. The sex ratio was calculated for different age groups including newborns delivered, patients attending OPD (0-12 y), children attending immunization centre (0-5 y), patients admitted in pediatric wards segregated in different age groups i.e., < 1 y, 1-4 y, 5-9 y and 10-14 y. Chi square test was used to find out if there was any variation in the sex ratio of patients attending the hospital against the sex ratio in the community. RESULTS: The mean sex ratio of patients (0-12 y) attending the pediatric OPD was 726 which is significantly lower than the sex ratio in the community (p < 0.00001). The sex ratio of patients (0-5 y) visiting immunization centre (846) was also significantly lower than sex ratio in the community (p = 0.0343). Among children delivered in the hospital mean sex ratio at birth was 934 against a sex ratio of 920 at birth in the reference population. The sex ratio of admitted patients was significantly lower in age groups <1 y (617, p value < 0.00001), 1-4 y (665, p value <0.00001), 5-9 y (665, p value <0.05). But the sex ratio improved for inpatients in the age group 10-14 y (794, p = 0.08). CONCLUSIONS: There is a strong bias against females for seeking medical attention both for outpatient and inpatient care. The bias is more for females in younger age groups as compared to adolescents. PMID- 26666906 TI - Iron Stores in Term and Late Preterm Small for Gestational Age and Appropriate for Gestational Age Neonates at Birth and in Early Infancy. AB - OBJECTIVE: To compare body iron stores in late preterm and term small for gestational age (SGA) infants with gestation matched appropriate-for-gestational age (AGA) infants at birth and at 2 mo of age. METHODS: In this prospective observational study, live births of 34-42 wk gestation and SGA (<10th centile for GA) were enrolled along with gestation matched AGA (10th-90th centile for GA) infants. Infants' blood samples were taken within 2 h of delivery, and repeated at 60 +/- 7 d of life. Primary outcome was serum ferritin at birth and 60 d of age. Secondary outcomes were hematocrit at birth and 60 d and need for transfusion until 60 d of life. RESULTS: A total of 37 SGA (gestation 37.2 +/- 1.9 wk, birth weight 1861 +/- 401 g) and 30 AGA infants (gestation 37.3 +/- 1.9 wk, birth weight 2607 +/- 405 g) were enrolled in the study. There was no difference in the serum ferritin between AGA and SGA infants at birth {median [IQR]: 254.0 [214.3-293.8] vs. 259.7 [217.8-301.5] MUg/L; p = 0.85} or 60 d of life {147.2 [101.4-193.0] vs. 155.0 [106.6-203.6] MUg/L; p = 0.81}. Mean hematocrit was 55.5 +/- 9.6 vs. 52.4 +/- 5.0 at birth (p = 0.10) and 32.1 +/- 4.9 vs. 31.6 +/- 3.8 at 60 d (p = 0.77) in SGA and AGA infants respectively. No infant required blood transfusion during the study period. CONCLUSIONS: Iron stores of late preterm and term SGA infants are comparable to term AGA infants at birth and 2 mo of age. Recommendations on iron supplementation to these infants need to be formulated through appropriately designed randomized trials. PMID- 26666907 TI - Acute Respiratory Distress Syndrome: A Rare Complication in Pediatric Diabetic Ketoacidosis. AB - Cerebral edema (CE) and non cardiogenic pulmonary edema (acute respiratory distress syndrome, ARDS) are life-threatening complications of diabetic ketoacidosis (DKA). In contrast to CE complicating DKA, which is primarily reported in pediatric patients, ARDS is rarely described in this age group. Here, the authors present a child with DKA who developed both cerebral edema and ARDS during the course of her management. It is feasible that severe acidosis, hypotension, azotemia, hypoalbuminemia and the superimposed aggressive intravenous fluid administration were important risk factors for the development of cerebral edema and ARDS in the index patient. The report highlights the importance of early diagnosis and aggressive therapy in the management of ARDS, and summarizes the published literature on this rarely reported complication of pediatric DKA. PMID- 26666908 TI - Assessing the relationship between pharmacists' job satisfaction and over-the counter counselling at community pharmacies. AB - BACKGROUND: Community pharmacies have an increasing role in self-medication and community health is dependent on the quality of counselling services provided to patients. Some studies show that pharmacists' job satisfaction affects their work quality; other studies found that higher involvement in clinical services increases pharmacists' job satisfaction. OBJECTIVE: To test the relationship between job satisfaction and over-the-counter counselling practice at community pharmacies. SETTING: Community pharmacies in Lithuania. METHOD: A convenience sample (n = 305) of community pharmacists participated in the cross-sectional survey where they expressed satisfaction with job and reported on their over-the counter counselling behaviour on self-report scales. The Partial Least Squares Structural Equation Modelling approach was employed for data analysis. MAIN OUTCOME MEASURE: The strength of the relationship between job satisfaction and over-the-counter counselling service. RESULTS: A bidirectional relationship between job satisfaction and over-the-counter counselling service was found. In addition, job satisfaction and over-the-counter counselling quality depended on pharmacists' age. CONCLUSION: Organizations were recommended to create a counselling friendly environment that would increase pharmacists' job satisfaction and, in return, counselling quality. Also, additional motivation of the retired pharmacists, as well as development of counselling skills of the younger pharmacy workforce, were seen as a means to improve both organizational climate and counselling quality over the counter. PMID- 26666909 TI - Ensuring rigour and trustworthiness of qualitative research in clinical pharmacy. AB - The use of qualitative research methodology is well established for data generation within healthcare research generally and clinical pharmacy research specifically. In the past, qualitative research methodology has been criticized for lacking rigour, transparency, justification of data collection and analysis methods being used, and hence the integrity of findings. Demonstrating rigour in qualitative studies is essential so that the research findings have the "integrity" to make an impact on practice, policy or both. Unlike other healthcare disciplines, the issue of "quality" of qualitative research has not been discussed much in the clinical pharmacy discipline. The aim of this paper is to highlight the importance of rigour in qualitative research, present different philosophical standpoints on the issue of quality in qualitative research and to discuss briefly strategies to ensure rigour in qualitative research. Finally, a mini review of recent research is presented to illustrate the strategies reported by clinical pharmacy researchers to ensure rigour in their qualitative research studies. PMID- 26666910 TI - [Non-interventional study for the treatment of neutropenia: Use of pegfilgrastim for chemotherapy-induced neutropenia]. PMID- 26666911 TI - Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy. AB - The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease. PMID- 26666912 TI - High Current Emission from Patterned Aligned Carbon Nanotubes Fabricated by Plasma-Enhanced Chemical Vapor Deposition. AB - Vertically, carbon nanotube (CNT) arrays were successfully fabricated on hexagon patterned Si substrates through radio frequency plasma-enhanced chemical vapor deposition using gas mixtures of acetylene (C2H2) and hydrogen (H2) with Fe/Al2O3 catalysts. The CNTs were found to be graphitized with multi-walled structures. Different H2/C2H2 gas flow rate ratio was used to investigate the effect on CNT growth, and the field emission properties were optimized. The CNT emitters exhibited excellent field emission performance (the turn-on and threshold fields were 2.1 and 2.4 V/MUm, respectively). The largest emission current could reach 70 mA/cm(2). The emission current was stable, and no obvious deterioration was observed during the long-term stability test of 50 h. The results were relevant for practical applications based on CNTs. PMID- 26666913 TI - R4496C RyR2 mutation impairs atrial and ventricular contractility. AB - Ryanodine receptor (RyR2) is the major Ca(2+) channel of the cardiac sarcoplasmic reticulum (SR) and plays a crucial role in the generation of myocardial force. Changes in RyR2 gating properties and resulting increases in its open probability (Po) are associated with Ca(2+) leakage from the SR and arrhythmias; however, the effects of RyR2 dysfunction on myocardial contractility are unknown. Here, we investigated the possibility that a RyR2 mutation associated with catecholaminergic polymorphic ventricular tachycardia, R4496C, affects the contractile function of atrial and ventricular myocardium. We measured isometric twitch tension in left ventricular and atrial trabeculae from wild-type mice and heterozygous transgenic mice carrying the R4496C RyR2 mutation and found that twitch force was comparable under baseline conditions (30 degrees C, 2 mM [Ca(2+)]o, 1 Hz). However, the positive inotropic responses to high stimulation frequency, 0.1 uM isoproterenol, and 5 mM [Ca(2+)]o were decreased in R4496C trabeculae, as was post-rest potentiation. We investigated the mechanisms underlying inotropic insufficiency in R4496C muscles in single ventricular myocytes. Under baseline conditions, the amplitude of the Ca(2+) transient was normal, despite the reduced SR Ca(2+) content. Under inotropic challenge, however, R4496C myocytes were unable to boost the amplitude of Ca(2+) transients because they are incapable of properly increasing the amount of Ca(2+) stored in the SR because of a larger SR Ca(2+) leakage. Recovery of force in response to premature stimuli was faster in R4496C myocardium, despite the unchanged rates of recovery of L-type Ca(2+) channel current (ICa-L) and SR Ca(2+) content in single myocytes. A faster recovery from inactivation of the mutant R4496C channels could explain this behavior. In conclusion, changes in RyR2 channel gating associated with the R4496C mutation could be directly responsible for the alterations in both ventricular and atrial contractility. The increased RyR2 Po and fractional Ca(2+) release from the SR induced by the R4496C mutation preserves baseline contractility despite a slight decrease in SR Ca(2+) content, but cannot compensate for the inability to increase SR Ca(2+) content during inotropic challenge. PMID- 26666914 TI - Gating the glutamate gate of CLC-2 chloride channel by pore occupancy. AB - CLC-2 channels are dimeric double-barreled chloride channels that open in response to hyperpolarization. Hyperpolarization activates protopore gates that independently regulate the permeability of the pore in each subunit and the common gate that affects the permeability through both pores. CLC-2 channels lack classic transmembrane voltage-sensing domains; instead, their protopore gates (residing within the pore and each formed by the side chain of a glutamate residue) open under repulsion by permeant intracellular anions or protonation by extracellular H(+). Here, we show that voltage-dependent gating of CLC-2: (a) is facilitated when permeant anions (Cl(-), Br(-), SCN(-), and I(-)) are present in the cytosolic side; (b) happens with poorly permeant anions fluoride, glutamate, gluconate, and methanesulfonate present in the cytosolic side; (c) depends on pore occupancy by permeant and poorly permeant anions; (d) is strongly facilitated by multi-ion occupancy; (e) is absent under likely protonation conditions (pHe = 5.5 or 6.5) in cells dialyzed with acetate (an impermeant anion); and (f) was the same at intracellular pH 7.3 and 4.2; and (g) is observed in both whole-cell and inside-out patches exposed to increasing [Cl(-)]i under unlikely protonation conditions (pHe = 10). Thus, based on our results we propose that hyperpolarization activates CLC-2 mainly by driving intracellular anions into the channel pores, and that protonation by extracellular H(+) plays a minor role in dislodging the glutamate gate. PMID- 26666915 TI - Identification and Characterization of FTY720 for the Treatment of Human African Trypanosomiasis. AB - The screening of a focused library identified FTY720 (Fingolimod; Gilenya) as a potent selective antitrypanosomal compound active against Trypanosoma brucei gambiense and T. brucei rhodesiense, the causative agents of human African trypanosomiasis (HAT). This is the first report of trypanocidal activity for FTY720, an oral drug registered for the treatment of relapsing multiple sclerosis, and the characterization of sphingolipids as a potential new class of compounds for HAT. PMID- 26666916 TI - Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. AB - Pyramax is a pyronaridine (PYR)-artesunate (PA) combination for the treatment of uncomplicated malaria in adult and pediatric patients. A granule formulation of this combination is being developed for treatment of uncomplicated P. falciparum and P. vivax malaria in pediatric patients. The aims of this study were to describe the pharmacokinetics of PYR using a total of 1,085 blood PYR concentrations available from 349 malaria patients younger than 16 years of age with mild to moderate uncomplicated malaria and to confirm the dosing regimen for the pediatric granule formulation. Nonlinear mixed-effects modeling using NONMEM software was used to obtain the pharmacokinetic and inter- and intraindividual variability parameter estimates. The population pharmacokinetics of PYR were described by a two-compartment model with first-order absorption and elimination. Allometric scaling was implemented to address the effect of body weight on clearance and volume parameters. The final parameter estimates of PYR apparent clearance (CL/F), central volume of distribution (V2/F), peripheral volume of distribution (V3/F), intercompartmental clearance (Q/F), and absorption rate constant (Ka) were 377 liters/day, 2,230 liters, 3,230 liters, 804 liters/day and 17.9 day(-1), respectively. Covariate model building conducted using forward addition (P < 0.05) followed by backward elimination (P < 0.001) yielded two significant covariate-parameter relationships, i.e., age on V2/F and formulation on Ka. Evaluation of bootstrapping, visual predictive check, and condition number indicated that the final model displayed satisfactory robustness, predictive power, and stability. Simulations of PYR concentration-time profiles generated from the final model show similar exposures across pediatric weight ranges, supporting the proposed labeling for weight-based dosing of Pyramax granules. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00331136 [phase II study] and NCT00541385, NCT00403260, NCT00422084, and NCT00440999 [phase III studies]. The most recent phase III study was registered at pactr.org under registration no. PACTR201105000286876.). PMID- 26666917 TI - The Toxicity of a Novel Antifungal Compound Is Modulated by Endoplasmic Reticulum Associated Protein Degradation Components. AB - In a search for new antifungal compounds, we screened a library of 4,454 chemicals for toxicity against the human fungal pathogen Aspergillus fumigatus. We identified sr7575, a molecule that inhibits growth of the evolutionary distant fungi A. fumigatus, Cryptococcus neoformans, Candida albicans, and Saccharomyces cerevisiae but lacks acute toxicity for mammalian cells. To gain insight into the mode of inhibition, sr7575 was screened against 4,885 S. cerevisiae mutants from the systematic collection of haploid deletion strains and 977 barcoded haploid DAmP (decreased abundance by mRNA perturbation) strains in which the function of essential genes was perturbed by the introduction of a drug resistance cassette downstream of the coding sequence region. Comparisons with previously published chemogenomic screens revealed that the set of mutants conferring sensitivity to sr7575 was strikingly narrow, affecting components of the endoplasmic reticulum associated protein degradation (ERAD) stress response and the ER membrane protein complex (EMC). ERAD-deficient mutants were hypersensitive to sr7575 in both S. cerevisiae and A. fumigatus, indicating a conserved mechanism of growth inhibition between yeast and filamentous fungi. Although the unfolded protein response (UPR) is linked to ERAD regulation, sr7575 did not trigger the UPR in A. fumigatus and UPR mutants showed no enhanced sensitivity to the compound. The data from this chemogenomic analysis demonstrate that sr7575 exerts its antifungal activity by disrupting ER protein quality control in a manner that requires ERAD intervention but bypasses the need for the canonical UPR. ER protein quality control is thus a specific vulnerability of fungal organisms that might be exploited for antifungal drug development. PMID- 26666918 TI - Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone. AB - We examined the pharmacokinetic properties of vancomycin conjugated to a bone targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome. PMID- 26666919 TI - Comparison of Verona Integron-Borne Metallo-beta-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles. AB - Metallo-beta-lactamases (MBLs) are of increasing clinical significance; the development of clinically useful MBL inhibitors is challenged by the rapid evolution of variant MBLs. The Verona integron-borne metallo-beta-lactamase (VIM) enzymes are among the most widely distributed MBLs, with >40 VIM variants having been reported. We report on the crystallographic analysis of VIM-5 and comparison of biochemical and biophysical properties of VIM-1, VIM-2, VIM-4, VIM-5, and VIM 38. Recombinant VIM variants were produced and purified, and their secondary structure and thermal stabilities were investigated by circular dichroism analyses. Steady-state kinetic analyses with a representative panel of beta lactam substrates were carried out to compare the catalytic efficiencies of the VIM variants. Furthermore, a set of metalloenzyme inhibitors were screened to compare their effects on the different VIM variants. The results reveal only small variations in the kinetic parameters of the VIM variants but substantial differences in their thermal stabilities and inhibition profiles. Overall, these results support the proposal that protein stability may be a factor in MBL evolution and highlight the importance of screening MBL variants during inhibitor development programs. PMID- 26666920 TI - Correlation of beta-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program. AB - The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-beta-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of Enterobacteriaceae (excluding Proteeae and Serratia spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum beta-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC90, 2 to 4 MUg/ml) and aztreonam-avibactam (MIC90, 0.5 to 1 MUg/ml) consistently tested with low MIC values against colistin-resistant, ESBL positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were Klebsiella pneumoniae. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of Enterobacteriaceae demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning. PMID- 26666921 TI - Colistin-Resistant Acinetobacter baumannii Clinical Strains with Deficient Biofilm Formation. AB - In two pairs of clinical colistin-susceptible/colistin-resistant (Cst(s)/Cst(r)) Acinetobacter baumannii strains, the Cst(r) strains showed significantly decreased biofilm formation in static and dynamic assays (P < 0.001) and lower relative fitness (P < 0.05) compared with those of the Cst(s) counterparts. The whole-genome sequencing comparison of strain pairs identified a mutation converting a stop codon to lysine (*241K) in LpsB (involved in lipopolysaccharide [LPS] synthesis) in one Cst(r) strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other. PMID- 26666922 TI - GS-5806 Inhibits a Broad Range of Respiratory Syncytial Virus Clinical Isolates by Blocking the Virus-Cell Fusion Process. AB - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children. In addition, RSV causes significant morbidity and mortality in hospitalized elderly and immunocompromised patients. Currently, only palivizumab, a monoclonal antibody against the RSV fusion (F) protein, and inhaled ribavirin are approved for the prophylactic and therapeutic treatment of RSV, respectively. Therefore, there is a clinical need for safe and effective therapeutic agents for RSV infections. GS-5806, discovered via chemical optimization of a hit from a high-throughput antiviral-screening campaign, selectively inhibits a diverse set of 75 RSV subtype A and B clinical isolates (mean 50% effective concentration [EC50] = 0.43 nM). The compound maintained potency in primary human airway epithelial cells and exhibited low cytotoxicity in human cell lines and primary cell cultures (selectivity > 23,000-fold). Time of-addition and temperature shift studies demonstrated that GS-5806 does not block RSV attachment to cells but interferes with virus entry. Follow-up experiments showed potent inhibition of RSV F-mediated cell-to-cell fusion. RSV A and B variants resistant to GS-5806, due to mutations in F protein (RSV A, L138F or F140L/N517I, and RSV B, F488L or F488S), were isolated and showed cross resistance to other RSV fusion inhibitors, such as VP-14637, but remained fully sensitive to palivizumab and ribavirin. In summary, GS-5806 is a potent and selective RSV fusion inhibitor with antiviral activity against a diverse set of RSV clinical isolates. The compound is currently under clinical investigation for the treatment of RSV infection in pediatric, immunocompromised, and elderly patients. PMID- 26666923 TI - In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes. AB - Streptococcus suis serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as S. suis. This study evaluated the in vitro and in vivo antimicrobial activities of CEQ against four strains of S. suis serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (10(6) to 10(8) CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (Emax) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%fT>MIC) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (R(2) = 91% and R(2) = 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (P = 0.006) and a 2-fold exposure time (P = 0.01) were required for a 1-log kill using large inocula of 10(8) CFU/thigh. PMID- 26666924 TI - Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis. AB - This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis. PMID- 26666925 TI - Activity of Eravacycline against Escherichia coli Clinical Isolates Collected from U.S. Veterans in 2011 in Relation to Coresistance Phenotype and Sequence Type 131 Genotype. AB - Eravacycline is a novel broad-spectrum fluorocycline with potent Gram-negative activity, including for multidrug-resistant strains. Among 472 Escherichia coli clinical isolates from 24 Veterans Affairs medical centers (in 2011), divided equally as susceptible versus resistant to fluoroquinolones, broth microdilution eravacycline MICs were distributed unimodally, ranging from 0.03 to 1.0 MUg/ml (MIC50 of 0.125 MUg/ml, MIC90 of 0.25 MUg/ml). Eravacycline MICs were ~ 2-fold higher among fluoroquinolone-resistant, gentamicin-resistant, multidrug resistant, and sequence type 131 (ST131) isolates (P < 0.01 for each comparison). PMID- 26666926 TI - Antimicrobial Susceptibilities of Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans. AB - Nutritionally variant streptococci (NVS) are fastidious Gram-positive cocci comprised of the species Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans. NVS are an important cause of bacteremia and infective endocarditis (IE) associated with significant morbidity and mortality. Antimicrobial susceptibility testing (AST) was performed for 14 antimicrobials using the broth microdilution MIC method described in the Clinical and Laboratory Standards Institute (CLSI) M45 guideline. A total of 132 clinical NVS blood isolates collected from 2008 to 2014 were tested. Species level identification of NVS isolates was achieved by 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Ninety isolates were identified as G. adiacens, 37 as A. defectiva, and 5 as G. elegans. All isolates were susceptible to vancomycin (MIC90 = 1 MUg/ml), and none displayed high-level resistance to aminoglycosides. G. adiacens was considerably more susceptible to penicillin than A. defectiva (38.9% versus 10.8% of isolates susceptible) but was less susceptible to cephalosporins than was A. defectiva (43.3% versus 100% of isolates susceptible to ceftriaxone). Several isolates were resistant to levofloxacin (6%), erythromycin (51%), and clindamycin (10%). The MIC90 for daptomycin was >= 4 MUg/ml for G. adiacens and A. defectiva. G. elegans isolates were 100% susceptible to all antimicrobials tested, with the exception of erythromycin, to which only 20% were susceptible. This study provides antimicrobial susceptibility data for a recent collection of NVS and demonstrates important NVS species-related differences with respect to susceptibility to penicillin, cephalosporins, carbapenems, and daptomycin. Species-level identification of NVS organisms when susceptibility testing is not readily available may aid in treatment decisions. PMID- 26666927 TI - Virulence Genes in Expanded-Spectrum-Cephalosporin-Resistant and -Susceptible Escherichia coli Isolates from Treated and Untreated Chickens. AB - This study investigated antimicrobial resistance, screened for the presence of virulence genes involved in intestinal infections, and determined phylogenetic groups of Escherichia coli isolates from untreated poultry and poultry treated with ceftiofur, an expanded-spectrum cephalosporin. Results show that none of the 76 isolates appeared to be Shiga toxin-producing E. coli or enteropathogenic E. coli. All isolates were negative for the major virulence factors/toxins tested (ehxA, cdt, heat-stable enterotoxin [ST], and heat-labile enterotoxin [LT]). The few virulence genes harbored in isolates generally did not correlate with isolate antimicrobial resistance or treatment status. However, some of the virulence genes were significantly associated with certain phylogenetic groups. PMID- 26666928 TI - Effects of Stress, Reactive Oxygen Species, and the SOS Response on De Novo Acquisition of Antibiotic Resistance in Escherichia coli. AB - Strategies to prevent the development of antibiotic resistance in bacteria are needed to reduce the threat of infectious diseases to human health. The de novo acquisition of resistance due to mutations and/or phenotypic adaptation occurs rapidly as a result of interactions of gene expression and mutations (N. Handel, J. M. Schuurmans, Y. Feng, S. Brul, and B. H. Ter Kuile, Antimicrob Agents Chemother 58:4371-4379, 2014, http://dx.doi.org/10.1128/AAC.02892-14). In this study, the contribution of several individual genes to the de novo acquisition of antibiotic resistance in Escherichia coli was investigated using mutants with deletions of genes known to be involved in antibiotic resistance. The results indicate that recA, vital for the SOS response, plays a crucial role in the development of antibiotic resistance. Likewise, deletion of global transcriptional regulators, such as gadE or soxS, involved in pH homeostasis and superoxide removal, respectively, can slow the acquisition of resistance to a degree depending on the antibiotic. Deletion of the transcriptional regulator soxS, involved in superoxide removal, slowed the acquisition of resistance to enrofloxacin. Acquisition of resistance occurred at a lower rate in the presence of a second stress factor, such as a lowered pH or increased salt concentration, than in the presence of optimal growth conditions. The overall outcome suggests that a central cellular mechanism is crucial for the development of resistance and that genes involved in the regulation of transcription play an essential role. The actual cellular response, however, depends on the class of antibiotic in combination with environmental conditions. PMID- 26666929 TI - Defining Clinical Exposures of Cefepime for Gram-Negative Bloodstream Infections That Are Associated with Improved Survival. AB - The percentage of time that free drug concentrations remain above the MIC (fT>MIC) that is necessary to prevent mortality among cefepime-treated patients with Gram-negative bloodstream infections (GNBSI) is poorly defined. We conducted a retrospective study of adult patients with GNBSI. Eligible cases were frequency matched to ensure categorical representation from all MICs. Organism, MIC, infection source, gender, age, serum creatinine, weight, antibiotic history, and modified APACHE II score were collected from hospital records. Two population pharmacokinetic models (models 1 and 2) were used to impute exposures over the first 24 h in each patient from mean model parameters, covariates, and dosing history. From the imputed exposures, survival thresholds for fT>MIC were identified using classification and regression tree (CART) analysis and analyzed as nominal variables for univariate and multivariate regressions. A total of 180 patients were included in the analysis, of whom 13.9% died and 86.1% survived. Many patients (46.7% [n = 84/180]) received combination therapy with cefepime. Survivors had higher mean (standard deviation [SD]) fT>MIC than those who died (model 1, 74.2% [29.6%] versus 52.1% [33.8%], P < 0.001; model 2, 85.9% [24.0%] versus 64.4% [31.4%], P < 0.001). CART identified fT>MIC threshold values for greater survival according to models 1 and 2 at >68% and >74%, respectively. Survival was improved for those with fT>MIC of >68% (model 1 adjusted odds ratio [aOR], 7.12; 95% confidence interval [CI], 1.90 to 26.7; P = 0.004) and >74% (model 2 aOR, 6.48; 95% CI, 1.90 to 22.1) after controlling for clinical covariates. Similarly, each 1% increase in cefepime fT>MIC resulted in a 2% improvement in multivariate survival probability (P = 0.015). Achieving a cefepime fT>MIC of 68 to 74% was associated with a higher odds of survival for patients with GNBSI. Regimens targeting this exposure should be aggressively pursued. PMID- 26666930 TI - Emergence of OXA-162 Carbapenemase- and DHA-1 AmpC Cephalosporinase-Producing Sequence Type 11 Klebsiella pneumoniae Causing Community-Onset Infection in Greece. AB - OXA-48-like carbapenemases have only recently emerged in Europe. OXA-162 is a rare OXA-48 variant usually coexpressed with extended-spectrum beta-lactamases. Here, we report the identification of the first OXA-162 carbapenemase-producing Klebsiella pneumoniae isolates, which coexpressed an AmpC cephalosporinase (DHA 1), retrieved from a patient in Greece. They belonged to a single sequence type (ST11) and caused the first documented community-onset urinary tract infections attributable to an OXA-48-like-producing Enterobacteriaceae strain. PMID- 26666931 TI - Discovery of Dual-Stage Malaria Inhibitors with New Targets. AB - Malaria remains a major global health problem, with more than half of the world population at risk of contracting the disease and nearly a million deaths each year. Here, we report the discovery of inhibitors that target multiple stages of malaria parasite growth. To identify these inhibitors, we took advantage of the Tres Cantos Antimalarial Compound Set (TCAMS) small-molecule library, which is comprised of diverse and potent chemical scaffolds with activities against the blood stage of the malaria parasite, and investigated their effects against the elusive liver stage of the malaria parasite using a forward chemical screen. From a screen of nearly 14,000 compounds, we identified and confirmed 103 compounds as dual-stage malaria inhibitors. Interestingly, these compounds show preferential inhibition of parasite growth in liver- versus blood-stage malaria parasite assays, highlighting the drug susceptibility of this parasite form. Mode-of action studies were completed using genetically modified and drug-resistant Plasmodium parasite strains. While we identified some compound targets as classical antimalarial pathways, such as the mitochondrial electron transport chain through cytochrome bc1 complex inhibition or the folate biosynthesis pathway, most compounds induced parasite death through as yet unknown mechanisms of action. Importantly, the identification of new chemotypes with different modes of action in killing Plasmodium parasites represents a promising opportunity for probing essential and novel molecular processes that remain to be discovered. The chemical scaffolds identified with activity against drug-resistant Plasmodium parasites represent starting points for dual-stage antimalarial development to surmount the threat of malaria parasite drug resistance. PMID- 26666932 TI - Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae. AB - Antibiotic-resistant strains of Klebsiella pneumoniae often exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL) positive Klebsiella pneumoniae with different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host. PMID- 26666933 TI - Role of the Outer Membrane and Porins in Susceptibility of beta-Lactamase Producing Enterobacteriaceae to Ceftazidime-Avibactam. AB - This study examined the activity of the novel antimicrobial combination ceftazidime-avibactam against Enterobacteriaceae exhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates of Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine beta-naphthylamide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes of E. coli and K. pneumoniae. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane of E. aerogenes, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazidime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species of Enterobacteriaceae studied were <= 8 mg/liter, regardless of outer membrane permeability changes resulting from an absence of defined porin proteins or upregulation of efflux. PMID- 26666934 TI - Evolution of AbGRI2-0, the Progenitor of the AbGRI2 Resistance Island in Global Clone 2 of Acinetobacter baumannii. AB - A320, isolated in the Netherlands in 1982 and also known as RUH134, is the earliest available multiply antibiotic-resistant (MAR) Acinetobacter baumannii isolate belonging to global clone 2 (GC2) and is the reference strain for this clone. The draft genome sequence of A320 was used to investigate the original location and configuration of the IS26-bounded AbGRI2 resistance island found in current GC2 isolates. PCR mapping and sequencing were used to order contigs composing the resistance islands. A320 contains two IS26-bounded resistance islands, AbGRI2-0a and AbGRI2-0b, of 7.8 kb and 25.4 kb, respectively. Together they contain blaTEM, aacC1, aadA1, sul1, catA1, and aphA1b genes, which confer resistance to antibiotics used clinically in the 1970s, as well as an incomplete mercury resistance module. Tracking the continuity of the chromosome and the target site duplications revealed that the two resistance islands were originally together as AbGRI2-0, an island of 32.4 kb, and were subsequently separated via an IS26-mediated intramolecular inversion that reversed the orientation of 1.54 Mb of the chromosome and duplicated an IS26. A320 contains an ancestral form of AbGRI2, and the original insertion site of the AbGRI2 island was identified. Many of the AbGRI2 versions present in the completed GC2 genomes can be derived from it via the variant AbGRI2-1. IS26-mediated inversions have also played a part in forming AbGRI2-0, and, upon reversal, large regions of AbGRI2-0 are identical to parts of AbaR0, the ancestral version of the AbaR islands present in GC1 isolates. This indicates a common source. PMID- 26666935 TI - Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques. AB - We evaluated the in vivo pharmacokinetics and used a complementary ex vivo coculture assay to determine the pharmacodynamics of IQB3002 gel containing 1% IQP-0528, a nonnucleoside reverse transcriptase inhibitor (NNRTI), in rhesus macaques (RM). The gel (1.5 ml) was applied vaginally to 6 simian-human immunodeficiency (SHIV)-positive female RM. Blood, vaginal fluids, and rectal fluids were collected at 0, 1, 2, and 4 h. RM were euthanized at 4 h, and vaginal, cervical, rectal, and regional lymph node tissues were harvested. Anti human immunodeficiency virus (HIV) activity was evaluated ex vivo by coculturing fresh or frozen vaginal tissues with activated human peripheral blood mononuclear cells (PBMCs) and measuring the p24 levels for 10 days after an HIV-1Ba-L challenge. The median levels of IQP-0528, determined using liquid chromatography tandem mass spectroscopy (LC-MS/MS) methods, were between 10(4) and 10(5) ng/g in vaginal and cervical tissue, between 10(3) and 10(4) ng/g in rectal tissues, and between 10(5) and 10(7) ng/ml in vaginal fluids over the 4-h period. The vaginal tissues protected the cocultured PBMCs from HIV-1 infection ex vivo, with a viral inhibition range of 81 to 100% in fresh and frozen tissues that were proximal, medial, and distal relative to the cervix. No viral inhibition was detected in untreated baseline tissues. Collectively, the median drug levels observed were 5 to 7 logs higher than the in vitro 50% effective concentration (EC50) range (0.21 ng/ml to 1.29 ng/ml), suggesting that 1.5 ml of the gel delivers IQP-0528 throughout the RM vaginal compartment at levels that are highly inhibitory to HIV 1. Importantly, antiviral activity was observed in both fresh and frozen vaginal tissues, broadening the scope of the ex vivo coculture model for future NNRTI efficacy studies. PMID- 26666936 TI - beta-Lactamase Characterization of Gram-Negative Pathogens Recovered from Patients Enrolled in the Phase 2 Trials for Ceftazidime-Avibactam: Clinical Efficacies Analyzed against Subsets of Molecularly Characterized Isolates. AB - The correlation of the clinical efficacies of ceftazidime-avibactam and comparators (carbapenems) was evaluated against baseline Gram-negative isolates having characterized beta-lactam resistance mechanisms from complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) phase 2 trials. Enterobacteriaceae displaying ceftriaxone and/or ceftazidime MICs of >= 2 MUg/ml (69 isolates) and nonfermentative Gram-negative bacilli (NF-GNB [three isolates]) with ceftazidime MICs of >= 16 MUg/ml were characterized for their narrow- and extended-spectrum beta-lactamase (ESBL) content. Enterobacteriaceae (one isolate) and NF-GNB (three isolates) with imipenem/meropenem MICs of >= 2 and >= 16 MUg/ml, respectively, were tested for carbapenemases. All cUTI E. coli had the lineage background investigated (ST131-like versus non-ST131-like). The primary efficacy endpoint was microbiological response (eradication) at test of cure (TOC) for cUTI and clinical response (inferred microbiological eradication) at TOC for cIAI. A total of 34.1% of baseline cUTI (36.4%) and cIAI (33.1%) pathogens met the MIC-based screening criteria (screen positive). All screen positive cUTI pathogens were CTX-M-producing E. coli, except for one E. cloacae isolate with AmpC overexpression. The majority (66.7%) of screen-positive cIAI isolates produced CTX-M-type coupled with a diverse array of other beta lactamases. Similar favorable responses were observed with ceftazidime-avibactam (93.3%) and carbapenems (90.9%), when a non-ESBL Enterobacteriaceae isolate was recovered at the baseline visit. When an ESBL Enterobacteriaceae isolate was present, the favorable responses were 85.7% and 80.0% with ceftazidime-avibactam and carbapenems, respectively. Higher favorable responses were observed with ceftazidime-avibactam (75.0%) than with carbapenems (66.7%) when an ST131-like E. coli isolate was recovered at baseline, as when a non-ST131-like isolate was present (93.8% versus 86.7%, respectively). The efficacy of ceftazidime-avibactam was similar to that of carbapenems for treatment of cUTI and cIAI caused by ESBL organisms. PMID- 26666937 TI - Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria. AB - The global emergence of drug resistance in malaria is impeding the therapeutic efficacy of existing antimalarial drugs. Therefore, there is a critical need to develop an efficient drug delivery system to circumvent drug resistance. The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000). These formulations were found to be more effective than a comparable dose of free monensin in Plasmodium falciparum (3D7) cultures and established mice models of Plasmodium berghei strains NK65 and ANKA. Parasite killing was determined by a radiolabeled [(3)H]hypoxanthine incorporation assay (in vitro) and microscopic counting of Giemsa-stained infected erythrocytes (in vivo). The enhancement of antimalarial activity was dependent on the liposomal lipid composition and preferential uptake by infected red blood cells (RBCs). The antiplasmodial activity of monensin in SA liposome (50% inhibitory concentration [IC50], 0.74 nM) and SPC:Chol-liposome with 5 mol% DSPE-mPEG 2000 (IC50, 0.39 nM) was superior to that of free monensin (IC50, 3.17 nM), without causing hemolysis of erythrocytes. Liposomes exhibited a spherical shape, with sizes ranging from 90 to 120 nm, as measured by dynamic light scattering and high-resolution electron microscopy. Monensin in long-circulating liposomes of stearylamine with 5 mol% DSPE-mPEG 2000 in combination with free artemisinin resulted in enhanced killing of parasites, prevented parasite recrudescence, and improved survival. This is the first report to demonstrate that monensin in PEGylated stearylamine (SA) liposome has therapeutic potential against malaria infections. PMID- 26666938 TI - Risk Factors and Outcomes for Intestinal Carriage of AmpC-Hyperproducing Enterobacteriaceae in Intensive Care Unit Patients. AB - In a cohort of 1,209 intensive care unit (ICU) patients, the prevalence of intestinal colonization with high-level expressed AmpC cephalosporinase-producing Enterobacteriaceae (HLAC-PE) rose steadily from 2% at admission to 30% in patients with lengths of stay (LOS) exceeding 4 weeks. In multivariate analysis, LOS was the main predictor of carriage acquisition after adjustment on antimicrobial exposure. HLAC-PE infection occurred in 15% of carriers. Carriage and infection were associated with a marked increase in carbapenem consumption. PMID- 26666939 TI - Complete Sequence of a Novel IncR-F33:A-:B- Plasmid, pKP1034, Harboring fosA3, blaKPC-2, blaCTX-M-65, blaSHV-12, and rmtB from an Epidemic Klebsiella pneumoniae Sequence Type 11 Strain in China. AB - A high fosfomycin resistance rate was observed in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) in our previous study, but little is known about its mechanisms. In this study, we explored the prevalence of plasmid-mediated fosfomycin resistance determinants among fosfomycin-resistant KPC-KP strains from a Chinese university hospital and determined the complete sequence of a novel fosA3-carrying plasmid isolated from an epidemic K. pneumoniae sequence type (ST) 11 strain. A total of 97 KPC-KP strains were studied, of which 57 (58.8%) were resistant to fosfomycin, including 44 (45.4%) harboring fosA3 and 1 harboring fosA. All fosA3-positive strains belonged to the dominant ST11-pulse type (PT) A clone according to multilocus sequence typing and pulsed-field gel electrophoresis, suggesting clonal dissemination. The fosA positive isolate belonged to ST11-PTE. The fosA3-carrying plasmid pKP1034 is 136,848 bp in length and is not self-transmissible. It is a multireplicon plasmid belonging to IncR-F33:A-: B-. Besides fosA3, a variety of other resistance determinants, including blaKPC-2, rmtB, blaCTX-M-65, and blaSHV-12, are identified in pKP1034, which would allow for coselection of fosA3 by most beta lactams and/or aminoglycosides and facilitate its dissemination despite limited use of fosfomycin in China. Detailed comparisons with related plasmids revealed that pKP1034 is highly mosaic and might have evolved from alarming recombination of the blaKPC-2-carrying plasmid pKPC-LK30 from Taiwan and the epidemic fosA3 carrying plasmid pHN7A8 from mainland China. PMID- 26666940 TI - Emergence of cfr-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis. AB - Resistance to linezolid (LZD) in methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with cystic fibrosis (CF) is due mainly to ribosomal mutations. We report on four CF patients with LZD-resistant MRSA bronchopulmonary infections by strains carrying the cfr gene. Strains from one patient also harbored the G2576U mutation (23S rRNA) and the G139R substitution (L3 protein). All strains belonged to the epidemic clone ST125 MRSA IVc. Our results support the monitoring of LZD resistance emergence in CF and non-CF MRSA isolates. PMID- 26666941 TI - Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia. AB - The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4(+) cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b(low) CD11c(high) alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP. PMID- 26666942 TI - Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria. AB - Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.). PMID- 26666943 TI - Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate. AB - Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success. PMID- 26666944 TI - Evolution of Resistance to Continuously Increasing Streptomycin Concentrations in Populations of Escherichia coli. AB - The evolution of antibiotic resistance in bacteria has become one of the defining problems in modern biology. Bacterial resistance to antimicrobial therapy threatens to eliminate one of the pillars of the practice of modern medicine. Yet, in spite of the importance of this problem, only recently have the dynamics of the shift from antibiotic sensitivity to resistance in a bacterial population been studied. In this study, a novel chemostat method was used to observe the evolution of resistance to streptomycin in a sensitive population of Escherichia coli, which grew while the concentration of antibiotic was constantly increasing. The results indicate that resistant mutants remain at a low frequency for longer than expected and do not begin to rise to a high frequency until the antibiotic concentrations are above the measured MIC, creating a "lull period" in which there were few bacterial cells growing in the chemostats. Overall, mutants resistant to streptomycin were found in >60% of the experimental trial replicates. All of the mutants detected were found to have MICs far above the maximum levels of streptomycin to which they were exposed and reached a high frequency within 96 h. PMID- 26666945 TI - Evaluation of the 2-Aminomethylphenol JPC-2997 in Aotus Monkeys Infected with Plasmodium falciparum. PMID- 26666946 TI - Does Critical Illness Change Levofloxacin Pharmacokinetics? AB - Levofloxacin is commonly used in critically ill patients for which existing data suggest nonstandard dosing regimens should be used. The objective of this study was to compare the population pharmacokinetics of levofloxacin in critically ill and in non-critically ill patients. Adult patients with a clinical indication for levofloxacin were eligible for participation in this prospective pharmacokinetic study. Patients were given 500 mg or 750 mg daily by intravenous administration with up to 11 blood samples taken on day 1 or 2 of therapy. Plasma samples were analyzed and population pharmacokinetic analysis was undertaken using Pmetrics. Thirty-five patients (18 critically ill) were included. The mean (standard deviation [SD]) age, weight, and Cockcroft-Gault creatinine clearance for the critically ill and for the non-critically ill patients were 60.3 (16.4) and 72.0 (11.6) years, 78.5 (14.8) and 70.9 (15.8) kg, and 71.9 (65.8) and 68.2 (30.1) ml/min, respectively. A two-compartment linear model best described the data. Increasing creatinine clearance was the only covariate associated with increasing drug clearance. The presence of critical illness did not significantly affect any pharmacokinetic parameter. The mean (SD) parameter estimates were as follows: clearance, 8.66 (3.85) liters/h; volume of the central compartment (Vc), 41.5 (24.5) liters; intercompartmental clearance constants from central to peripheral, 2.58 (3.51) liters/h; and peripheral to central compartments, 0.90 (0.58) liters/h. Monte Carlo dosing simulations demonstrated that achievement of therapeutic exposures was dependent on renal function, pathogen, and MIC. Critical illness appears to have no independent effect on levofloxacin pharmacokinetics that cannot be explained by altered renal function. PMID- 26666947 TI - Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital. AB - One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Children's Hospital. Nosocomial S. aureus isolates (those causing infection at >=72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of >=2 MUg/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic tolerant S. aureus strains are common in our children's hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future. PMID- 26666948 TI - Biochemical Characterization of CPS-1, a Subclass B3 Metallo-beta-Lactamase from a Chryseobacterium piscium Soil Isolate. AB - CPS-1 is a subclass B3 metallo-beta-lactamase from a Chryseobacterium piscium isolate collected from soil, showing 68% amino acid identity to the GOB-1 enzyme. CPS-1 was overproduced in Escherichia coli Rosetta (DE3), purified by chromatography, and biochemically characterized. This enzyme exhibits a broad spectrum substrate profile, including penicillins, cephalosporins, and carbapenems, which overall resembles those of L1, GOB-1, and acquired subclass B3 enzymes AIM-1 and SMB-1. PMID- 26666949 TI - Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine. AB - Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 MUM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth assays. In contrast, chlorhexidine alone, at a similar concentration, showed limited effects. Notably, neomycin alone or conjugated with nanoparticles did not show amoebicidal or amoebistatic effects. Pretreatment of A. castellanii with gold-conjugated chlorhexidine nanoparticles reduced amoeba-mediated host cell cytotoxicity from 90% to 40% at 5 MUM. In contrast, chlorhexidine alone, at similar concentrations, had no protective effects for the host cells. Similarly, amoebae treated with neomycin alone or neomycin-conjugated nanoparticles showed no protective effects. Overall, these findings suggest that gold-conjugated chlorhexidine nanoparticles hold promise in the improved treatment of A. castellanii keratitis. PMID- 26666950 TI - In Vitro Activity of Retapamulin and Antimicrobial Susceptibility Patterns in a Longitudinal Collection of Methicillin-Resistant Staphylococcus aureus Isolates from a Veterans Affairs Medical Center. AB - Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial agents, including mupirocin, for 403 MRSA isolates collected longitudinally from a naive population at the Veterans Affairs Puget Sound Health Care System. The MICs for retapamulin had a unimodal distribution, ranging from 0.008 to 0.5 MUg/ml. One isolate had an MIC of >16 MUg/ml, was also resistant to clindamycin and erythromycin, and was recovered from the nares of a patient undergoing hemodialysis. Twenty-four isolates (6%) and 11 isolates (3%) demonstrated low-level resistance (MICs of 8 to 64 MUg/ml) and high-level resistance (MICs of >= 512 MUg/ml), respectively, to mupirocin. Isolates were recovered from 10 patients both before and after mupirocin therapy. Of those, isolates from 2 patients demonstrated MIC changes postmupirocin therapy; in both cases, however, strain typing demonstrated that the pre- and postmupirocin strains were different. A total of 386 isolates (96%) had vancomycin MICs of <= 1.0 MUg/ml; 340 isolates (84%) were resistant to levofloxacin, 18 isolates (4.5%) were resistant to trimethoprim-sulfamethoxazole, and 135 isolates (33%) had elevated MICs of 4 MUg/ml for linezolid. The baseline levels of resistance were low for mupirocin (9%) and even lower for retapamulin (0.25%) Although the use of mupirocin is currently the standard therapy for decolonization practices, the activity of retapamulin warrants its consideration as an alternative therapy in MRSA decolonization regimens. PMID- 26666951 TI - Erratum to: A novel thermostable protein-tag: optimization of the Sulfolobus solfataricus DNA-alkyl-transferase by protein engineering. PMID- 26666952 TI - Modulating the rate of charge transport in a metal-organic framework thin film using host:guest chemistry. AB - Herein we demonstrate the use of host-guest chemistry to modulate rates of charge transport in metal-organic framework (MOF) films. The kinetics of site-to-site of charge hopping and, in turn, the overall redox conductivity, of a ferrocene modified MOF can be altered by up to 30-fold by coupling electron exchange to the oxidation-state-dependent formation of inclusion complexes between cyclodextrin and channel-tethered metallocenes. PMID- 26666953 TI - NPM1 Mutation Detection in Acute Myeloid Leukemia: A Method Comparison Study. AB - BACKGROUND: Mutations in the nucleophosmin (NPM1) gene have been used as molecular biomarkers for prognostication of patients with adult acute myeloid leukemia (AML). METHODS: We designed a rapid and sensitive method using the allele-specific-refractory mutation system-polymerase chain reaction (ARMS-PCR) to detect the most common mutations of NPM1 gene, which are mostly four base pair insertions and compared its efficacy with direct sequencing and capillary electrophoresis which served as the gold standards. RESULTS: The incidence of mutation was 22% (33% of patients with normal karyotypes had mutation compared with 16% of patients with abnormal karyotypes) based on the results obtained with capillary electrophoresis analysis and direct sequencing. All of the specimens determined to be mutation-positive by the gold standard tests were also positive by the ARMS-PCR method. Significantly, the ARMS-PCR test also helped determine the mutation status of an extra set of patients who had low call rates on capillary electrophoresis and appeared normal on direct sequencing. DISCUSSION: The low mutation rate in some patients hindered its detection in the gold standard assays because of the interference of the mutation signal by high background noise. The low sensitivity of the gold standard assays for detecting low copy number mutations rates thus increase their risk of producing false negative results that adversely affects prognostication and therapy. Our results suggest that the mutation detection rate of the ARMS-PCR assay is better than existing tests. This is most probably because of the fact that in an ARMS-PCR based method, the mutated variant is specifically amplified, based on a mutation specific primer. CONCLUSIONS: We conclude that the high sensitivity of the ARMS based method together with its rapidity and low expense should make it a suitable choice for clinical laboratories. PMID- 26666954 TI - Erratum to: Nature apps: Waiting for the revolution. PMID- 26666955 TI - Rapid re-oxygenation of Baltic Sea sediments following a large inflow event. PMID- 26666956 TI - Philippine protected areas are not meeting the biodiversity coverage and management effectiveness requirements of Aichi Target 11. AB - Aichi Target 11 of the Convention on Biological Diversity urges, inter alia, that nations protect at least 17 % of their land, and that protection is effective and targets areas of importance for biodiversity. Five years before reporting on Aichi targets is due, we assessed the Philippines' current protected area system for biodiversity coverage, appropriateness of management regimes and capacity to deliver protection. Although protected estate already covers 11 % of the Philippines' land area, 64 % of its key biodiversity areas (KBAs) remain unprotected. Few protected areas have appropriate management and governance infrastructures, funding streams, management plans and capacity, and a serious mismatch exists between protected area land zonation regimes and conservation needs of key species. For the Philippines to meet the biodiversity coverage and management effectiveness elements of Aichi Target 11, protected area and KBA boundaries should be aligned, management systems reformed to pursue biodiversity led targets and effective management capacity created. PMID- 26666958 TI - Multicompartment metabolism in papillary thyroid cancer. AB - OBJECTIVES/HYPOTHESIS: In many cancers, varying regions within the tumor are often phenotypically heterogeneous, including their metabolic phenotype. Further, tumor regions can be metabolically compartmentalized, with metabolites transferred between compartments. When present, this metabolic coupling can promote aggressive behavior. Tumor metabolism in papillary thyroid cancer (PTC) is poorly characterized. STUDY DESIGN: Immunohistochemical staining of tissue samples. METHODS: Papillary thyroid cancer specimens from 46 patients with (n = 19) and without advanced disease (n = 27) were compared to noncancerous thyroid tissue (NCT) and benign thyroid specimens (n = 6 follicular adenoma [FA] and n = 5 nodular goiter [NG]). Advanced disease was defined as the presence of lateral neck lymphadenopathy. Immunohistochemistry was performed for translocase of outer mitochondrial membrane 20 (TOMM20), a marker of oxidative phosphorylation, and monocarboxylate transporter 4 (MCT4), a marker of glycolysis. RESULTS: Papillary thyroid cancer and FA thyrocytes had high staining for TOMM20 compared to NCT and nodular goiter (NG) (P < 0.01). High MCT4 staining in fibroblasts was more common in PTC with advanced disease than in any other tissue type studied (P < 0.01). High MCT4 staining was found in all 19 cases of PTC with advanced disease, in 11 of 19 samples with low-stage disease, in one of five samples of FA, in one of 34 NCT, and in 0 of six NG samples. Low fibroblast MCT4 staining in PTC correlated with the absence of clinical adenopathy (P = 0.028); the absence of extrathyroidal extension (P = 0.004); low American Thyroid Association risk (P = 0.001); low AGES (age, grade, extent, size) score (P = 0.004); and low age, metastasis, extent of disease, size risk (P = 0.002). CONCLUSION: This study suggests that multiple metabolic compartments exist in PTC, and low fibroblast MCT4 may be a biomarker of indolent disease. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:2410-2418, 2016. PMID- 26666959 TI - Sporogony and sporozoite rates of avian malaria parasites in wild Culex pipiens pallens and C. inatomii in Japan. AB - BACKGROUND: Malaria infection in mosquitoes is traditionally detected by microscopic examination for Plasmodium oocysts and sporozoites. Although PCR is now widely used, the presence of parasite DNA in a mosquito does not prove that sporogony is achieved. Thus, detection of sporozoites by microscopy is still required to definitively identify vector mosquitoes. The aim of this study was to confirm sporogony of avian Plasmodium spp. in Culex pipiens pallens and C. inatomii caught from the wild. FINDINGS: Mosquitoes collected at two sites in Japan were dissected and examined by microscopy for Plasmodium oocysts and sporozoites. DNA was extracted from the midgut and salivary gland of infected mosquitoes, and the infecting Plasmodium species was identified by sequencing 478 bp of cytochrome b. Oocysts, or both oocysts and sporozoites, were found in 3.94 and 0.46% of C. p. pallens and C. inatomii, respectively. Four (CXPIP09, GRW4, GRW11 and SGS1) and three cytochrome b lineages (CXINA01, CXINA02 and CXQUI01) were confirmed to achieve sporogony in C. p. pallens and C. inatomii, respectively. One mosquito each of C. p. pallens and C. inatomii was co-infected with two different Plasmodium lineages. CONCLUSIONS: These findings demonstrate that C. p. pallens and C. inatomii are natural vectors of four and three lineages of avian Plasmodium spp., respectively. The data indicate that a systematic procedure combining microscopy and PCR is a feasible and reliable approach to identify natural vectors of wildlife malaria. PMID- 26666960 TI - An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding. AB - Previous research has focused on feeding circuits residing in the hindbrain and midbrain that govern homeostatic or hedonic control of food intake. However, the feeding circuits controlling emotional or cognitive aspects of food intake are largely unknown. Here we use chemical genetics and optogenetic techniques to dissect appetite control circuits originating from ventral hippocampus (vHPC), a brain region implicated in emotion and cognition. We find that the vHPC projects functional glutamatergic synaptic inputs to the lateral septum (LS) and optogenetic activation of vHPC projections in LS reduces food intake. Consistently, food intake is suppressed by chemogenetic activation of glutamatergic neurons in the vHPC that project to the LS and inactivation of LS neurons blunts vHPC-induced suppression of feeding. Collectively, our results identify an anorexigenic neural circuit originating from vHPC to LS in the brain, revealing a potential therapeutic target for the treatment of anorexia or other appetite disorders. PMID- 26666961 TI - Interventional therapy in sarcoidosis-associated pulmonary arterial stenosis and pulmonary hypertension. AB - BACKGROUNDS: Pulmonary sarcoidosis is often complicated by pulmonary hypertension, a complication that is associated with increased disability and mortality. To this point, however, little progress has been made in the treatment of sarcoidosis associated with pulmonary hypertension (SAPH). METHODS: A prospective study was performed on 72 consecutive Chinese sarcoidosis patients followed at an outpatient clinic. The patients were evaluated by Doppler echocardiography and computed tomography pulmonary angiography. SAPH was confirmed by right heart catheterisation. The clinical parameters were compared before and 2 months after treatment with oral glucocorticoids. Eight stage III and IV patients with moderate to severe proximal pulmonary arterial stenosis (PAS) and SAPH underwent interventional therapy (IT) after prednisone treatment and were followed up at 3-month intervals. RESULTS: After 2 months of prednisone treatment, 32 stage III and IV patients continued to display varying degrees of PAS and SAPH. Eight patients underwent IT without severe complications and made improvements in pulmonary arterial pressure, pulmonary vascular resistance, arterial oxygen saturation and WHO functional classification, with the improvements lasting more than 3 months. CONCLUSIONS: PAS caused by external compression in sarcoidosis is a significant reason for SAPH. IT is effective and safe in the treatment of PAS and SAPH. PMID- 26666962 TI - Two domain-disrupted hda6 alleles have opposite epigenetic effects on transgenes and some endogenous targets. AB - HDA6 is a RPD3-like histone deacetylase. In Arabidopsis, it mediates transgene and some endogenous target transcriptional gene silencing (TGS) via histone deacetylation and DNA methylation. Here, we characterized two hda6 mutant alleles that were recovered as second-site suppressors of the DNA demethylation mutant ros1-1. Although both alleles derepressed 35S::NPTII and RD29A::LUC in the ros1-1 background, they had distinct effects on the expression of these two transgenes. In accordance to expression profiles of two transgenes, the alleles have distinct opposite methylation profiles on two reporter gene promoters. Furthermore, both alleles could interact in vitro and in vivo with the DNA methyltransferase1 with differential interactive strength and patterns. Although these alleles accumulated different levels of repressive/active histone marks, DNA methylation but not histone modifications in the two transgene promoters was found to correlate with the level of derepression of the reporter genes between the two had6 alleles. Our study reveals that mutations in different domains of HDA6 convey different epigenetic status that in turn controls the expression of the transgenes as well as some endogenous loci. PMID- 26666963 TI - IL-31-induced pruritus in dogs: a novel experimental model to evaluate anti pruritic effects of canine therapeutics. AB - BACKGROUND: Pruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL-31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs. HYPOTHESIS/OBJECTIVES: The objectives were to characterize an IL-31-induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti pruritic effects of oclacitinib against those of prednisolone and dexamethasone. ANIMALS: Purpose-bred beagle dogs were used in all studies. METHODS: Randomized, blinded, placebo-controlled studies were designed to evaluate and compare the anti-pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL-31. Video surveillance was used to monitor and score pruritic behaviours in study animals. RESULTS: Prednisolone [0.5 mg/kg, per os (p.o.)] reduced IL-31-induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL-31-induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti-pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed. CONCLUSION AND CLINICAL IMPORTANCE: The efficacy of prednisolone, dexamethasone and oclacitinib in the IL-31-induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations. PMID- 26666964 TI - A comparison of stroke rehabilitation; data from two national cohorts. AB - OBJECTIVES: Inpatient rehabilitation is a commonly used complex intervention to improve a person's independence after stroke. Evaluation and comparison of the effects of routine clinical practice could provide a contribution towards optimization of stroke care. The aim of this study is to describe results of inpatient rehabilitation as a complex intervention for persons after stroke and explore possible differences between two countries. METHODS: Data from 1055 Latvian and 1748 Swedish adult patients after stroke receiving inpatient rehabilitation, during 2011-2013, were used for this retrospective cohort study. Qualitative description of systems, as well as information on basic medical and sociodemographic information, and organizational aspects were reported. Change in the Functional Independence Measure during rehabilitation was investigated. In six domains of the instrument, the shifts for three levels of dependence were analysed using ordinal regression analysis. RESULTS: The components of stroke care seem to be similar in Latvia and Sweden. However, the median time since stroke onset until the start of rehabilitation was 13 weeks in Latvia and 2 weeks in Sweden. The median length of rehabilitation was 12 and 49 days, respectively. The level of dependency at start, time since stroke onset and length of the period had an impact on the results of the rehabilitation. CONCLUSIONS: Although components of the rehabilitation are reported as being the same, characteristics and the outcome of the inpatient rehabilitation are different. Therefore, comparison of stroke rehabilitation between countries requires caution. PMID- 26666965 TI - Inhibition of macrophage-derived foam cell formation by ezetimibe via the caveolin-1/MAPK pathway. AB - Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, effectively reduces plasma cholesterol, but its effect on atherosclerosis is unclear. Foam cell formation has been implicated as a key mediator during the development of atherosclerosis. The purpose of this study was to investigate the effects of ezetimibe on foam cell formation and explore the underlying mechanism. The results presented here show that ezetimibe reduces atherosclerotic lesions in apolipoprotein E deficient (apoE-/-) mice by lowering cholesterol levels. Treatment of macrophages with Chol:MbetaCD resulted in foam cell formation, which was concentration-dependently inhibited by the presence of ezetimibe. Mechanically, ezetimibe treatment downregulated the expression of CD36 and scavenger receptor class B1 (SR-B1), but upregulated the expression of apoE and caveolin-1 in macrophage-derived foam cells, which kept consistent with our microarray results. Moreover, treatment with ezetimibe abrogated the increase of phospho-extracellular signal regulated kinase (ERK) 1/2 and their nuclear accumulation in foam cells. Inhibition of the MAPK pathway by the MEK inhibitor PD98059 attenuated the inhibitory effect of ezetimibe on the expression of p ERK1/2 and caveolin-1. Taken together, these results showed that ezetimibe suppressed foam cell formation via the caveolin-1/MAPK signalling pathway, suggesting that inhibition of foam cell formation might be a novel mechanism underlying the anti-atherosclerotic effect of ezetimibe. PMID- 26666966 TI - Risk Assessment in Criminal Sentencing. AB - The past several years have seen a surge of interest in using risk assessment in criminal sentencing, both to reduce recidivism by incapacitating or treating high risk offenders and to reduce prison populations by diverting low-risk offenders from prison. We begin by sketching jurisprudential theories of sentencing, distinguishing those that rely on risk assessment from those that preclude it. We then characterize and illustrate the varying roles that risk assessment may play in the sentencing process. We clarify questions regarding the various meanings of "risk" in sentencing and the appropriate time to assess the risk of convicted offenders. We conclude by addressing four principal problems confronting risk assessment in sentencing: conflating risk and blame, barring individual inferences based on group data, failing adequately to distinguish risk assessment from risk reduction, and ignoring whether, and if so, how, the use of risk assessment in sentencing affects racial and economic disparities in imprisonment. PMID- 26666967 TI - The Importance of Considering Clinical Utility in the Construction of a Diagnostic Manual. AB - The development of major diagnostic manuals primarily has been guided by construct validity rather than clinical utility. The purpose of this article is to summarize recent research and theory examining the importance of clinical utility when constructing and evaluating a diagnostic manual. We suggest that construct validity is a necessary but not sufficient criterion for diagnostic constructs. This article discusses components of clinical utility and how these have applied to the current and forthcoming diagnostic manuals. Implications and suggestions for future research are provided. PMID- 26666968 TI - The Neurobiology of Intervention and Prevention in Early Adversity. AB - Early adverse experiences are well understood to affect development and well being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy. PMID- 26666969 TI - The Relevance of the Affordable Care Act for Improving Mental Health Care. AB - Provisions of the Affordable Care Act provide unprecedented opportunities for expanded access to behavioral health care and for redesigning the provision of services. Key to these reforms is establishing mental and substance abuse care as essential coverage, extending Medicaid eligibility and insurance parity, and protecting insurance coverage for persons with preexisting conditions and disabilities. Many provisions, including Accountable Care Organizations, health homes, and other structures, provide incentives for integrating primary care and behavioral health services and coordinating the range of services often required by persons with severe and persistent mental health conditions. Careful research and experience are required to establish the services most appropriate for primary care and effective linkage to specialty mental health services. Research providing guidance on present evidence and uncertainties is reviewed. Success in redesign will follow progress building on collaborative care and other evidence based practices, reshaping professional incentives and practices, and reinvigorating the behavioral health workforce. PMID- 26666970 TI - MycoCAP - Mycobacterium Comparative Analysis Platform. AB - Mycobacterium spp. are renowned for being the causative agent of diseases like leprosy, Buruli ulcer and tuberculosis in human beings. With more and more mycobacterial genomes being sequenced, any knowledge generated from comparative genomic analysis would provide better insights into the biology, evolution, phylogeny and pathogenicity of this genus, thus helping in better management of diseases caused by Mycobacterium spp.With this motivation, we constructed MycoCAP, a new comparative analysis platform dedicated to the important genus Mycobacterium. This platform currently provides information of 2108 genome sequences of at least 55 Mycobacterium spp. A number of intuitive web-based tools have been integrated in MycoCAP particularly for comparative analysis including the PGC tool for comparison between two genomes, PathoProT for comparing the virulence genes among the Mycobacterium strains and the SuperClassification tool for the phylogenic classification of the Mycobacterium strains and a specialized classification system for strains of Mycobacterium abscessus. We hope the broad range of functions and easy-to-use tools provided in MycoCAP makes it an invaluable analysis platform to speed up the research discovery on mycobacteria for researchers. Database URL: http://mycobacterium.um.edu.my. PMID- 26666971 TI - pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area. AB - A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM(-1) s(-1). To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4 loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues. PMID- 26666972 TI - Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi. AB - Fruit pathogens can contribute to the acidification or alkalinization of the host environment. This capability has been used to divide fungal pathogens into acidifying and/or alkalinizing classes. Here, we show that diverse classes of fungal pathogens-Colletotrichum gloeosporioides, Penicillium expansum, Aspergillus nidulans and Fusarium oxysporum-secrete small pH-affecting molecules. These molecules modify the environmental pH, which dictates acidic or alkaline colonizing strategies, and induce the expression of PACC-dependent genes. We show that, in many organisms, acidification is induced under carbon excess, i.e. 175 mm sucrose (the most abundant sugar in fruits). In contrast, alkalinization occurs under conditions of carbon deprivation, i.e. less than 15 mm sucrose. The carbon source is metabolized by glucose oxidase (gox2) to gluconic acid, contributing to medium acidification, whereas catalysed deamination of non preferred carbon sources, such as the amino acid glutamate, by glutamate dehydrogenase 2 (gdh2), results in the secretion of ammonia. Functional analyses of Deltagdh2 mutants showed reduced alkalinization and pathogenicity during growth under carbon deprivation, but not in high-carbon medium or on fruit rich in sugar, whereas analysis of Deltagox2 mutants showed reduced acidification and pathogencity under conditions of excess carbon. The induction pattern of gdh2 was negatively correlated with the expression of the zinc finger global carbon catabolite repressor creA. The present results indicate that differential pH modulation by fruit fungal pathogens is a host-dependent mechanism, affected by host sugar content, that modulates environmental pH to enhance fruit colonization. PMID- 26666973 TI - True Density Prediction of Garlic Slices Dehydrated by Convection. AB - Physiochemical parameters with constant values are employed for the mass-heat transfer modeling of the air drying process. However, structural properties are not constant under drying conditions. Empirical, semi-theoretical, and theoretical models have been proposed to describe true density (rhop). These models only consider the ideal behavior and assume a linear relationship between rhop and moisture content (X); nevertheless, some materials exhibit a nonlinear behavior of rhop as a function of X with a tendency toward being concave-down. This comportment, which can be observed in garlic and carrots, has been difficult to model mathematically. This work proposes a semi-theoretical model for predicting rhop values, taking into account the concave-down comportment that occurs at the end of the drying process. The model includes the rhos dependency on external conditions (air drying temperature (Ta)), the inside temperature of the garlic slices (Ti ), and the moisture content (X) obtained from experimental data on the drying process. Calculations show that the dry solid density (rhos ) is not a linear function of Ta, X, and Ti . An empirical correlation for rhos is proposed as a function of Ti and X. The adjustment equation for Ti is proposed as a function of Ta and X. The proposed model for rhop was validated using experimental data on the sliced garlic and was compared with theoretical and empirical models that are available in the scientific literature. Deviation between the experimental and predicted data was determined. An explanation of the nonlinear behavior of rhos and rhop in the function of X, taking into account second-order phase changes, are then presented. PMID- 26666974 TI - van der Waals Heterojunction Devices Based on Organohalide Perovskites and Two Dimensional Materials. AB - The recently emerged organohalide perovskites (e.g., CH3NH3PbI3) have drawn intense attention for high efficiency solar cells. However, with a considerable solubility in many solvents, these perovskites are not typically compatible with conventional lithography processes for more complicated device fabrications that are important for both fundamental studies and technological applications. Here, we report the creation of novel heterojunction devices based on perovskites and two-dimensional (2D) crystals by taking advantage of the layered characteristic of lead iodide (PbI2) and vapor-phase intercalation. We show that a graphene/perovskite/graphene vertical stack can deliver a highest photoresponsivity of ~950 A/W and photoconductive gain of ~2200, and a graphene/WSe2/perovskite/graphene heterojunction can display a high on/off ratio (~10(6)) transistor behavior with distinct gate-tunable diode characteristics and open-circuit voltages. Such unique perovskite-2D heterostructures have significant potential for future optoelectronic research and can enable broad possibilities with compositional tunability of organohalide perovskites and the versatility offered by diverse 2D materials. PMID- 26666976 TI - Physician, Monitor Thyself. PMID- 26666975 TI - DeFiNe: an optimisation-based method for robust disentangling of filamentous networks. AB - Thread-like structures are pervasive across scales, from polymeric proteins to root systems to galaxy filaments, and their characteristics can be readily investigated in the network formalism. Yet, network links usually represent only parts of filaments, which, when neglected, may lead to erroneous conclusions from network-based analyses. The existing alternatives to detect filaments in network representations require tuning of parameters over a large range of values and treat all filaments equally, thus, precluding automated analysis of diverse filamentous systems. Here, we propose a fully automated and robust optimisation based approach to detect filaments of consistent intensities and angles in a given network. We test and demonstrate the accuracy of our solution with contrived, biological, and cosmic filamentous structures. In particular, we show that the proposed approach provides powerful automated means to study properties of individual actin filaments in their network context. Our solution is made publicly available as an open-source tool, "DeFiNe", facilitating decomposition of any given network into individual filaments. PMID- 26666977 TI - Achilles Tendon Vascularization of Proximal, Medial, and Distal Portion Before and After Partial Lesion in Rats Treated with Phototherapy. AB - BACKGROUND: The Achilles tendon is one of the tendons most commonly injured by microtraumas and overuse during sports practice. This tendon is especially fragile because of the low blood supply in its central part. Nevertheless, the literature does not offer enough scientific support to explain the composition and vascular dynamic of animal tendons, despite the relevance of being able to observe if the animal tendon undergoes the same processes of vascularization in different regions, as occurs in humans. METHODS: We used 28 rats weighing 280 +/- 20 g, which were divided into four groups with seven animals each (control, sham, 830 nm, 660 nm). The laser parameters were: power output 60 mW for both lasers, 40 J/cm(2) of energy density, total energy 1.1 J, power density 2.14 W/cm(2), and application time 18.6 sec. This study evaluated the vascular constitution of healthy and injured calcaneous tendons. The tendons of each animal were processed to be embedded in Paraplast and, after that, they were divided into three parts: proximal, medial, and distal. Afterwards, they were cut in slices of 6 MUm were made, then they were stained with hematoxylin and eosin. Using an ocular lens reticulated with magnification * 400, we analyzed the number and the area density of the blood vessels using morphometric methods. Data were analyzed with the Shapiro-Wilk test, followed by Tukey, considering p as <0.05. RESULTS: The area density and the number of blood vessels in the proximal part were 36% and 42%, respectively, of the values found in the medial part. The distal part had 64% more vessels and 52.8% more area density (p < 0.05) than the medial part. CONCLUSIONS: Low-level laser therapy (LLLT) had no effect on the studied parameters. The vascularization of rat tendon is similar to that of humans, which contributes to the studies of therapies that have been applied in humans. PMID- 26666978 TI - Pressure ulcers: treatment. AB - INTRODUCTION: Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers in up to one third of people in hospitals or community care, and one fifth of nursing home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments in people with pressure ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 307 studies. After deduplication and removal of conference abstracts, 203 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 163 studies and the further review of 40 full publications. Of the 40 full articles evaluated, seven systematic reviews and two RCTs were added at this update. We performed a GRADE evaluation for 15 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 15 interventions based on information about the effectiveness and safety of air-fluidised supports, alternating-pressure surfaces (including mattresses), debridement, dressings, electrotherapy, hyperbaric oxygen, low-air-loss beds, low-level laser therapy, low-tech constant-low-pressure supports, nutritional supplements, seat cushions, surgery, therapeutic ultrasound, topical negative pressure, and topical phenytoin. PMID- 26666979 TI - Albumin and pre-albumin levels do not reflect the nutritional status of female adolescents with restrictive eating disorders. AB - AIM: Albumin and pre-albumin are frequently used as nutritional markers in clinical practice. We examined whether serum albumin and pre-albumin were predicted by body mass index (BMI), hydration and/or inflammation in female adolescents with a recently diagnosed restrictive eating disorder (RED). METHODS: This was a retrospective study of female adolescents with RED from 2002 to 2011. Low albumin and pre-albumin levels were defined as <3.5 g/dL and <20 mg/dL, respectively. We assessed inflammation using the erythrocyte sedimentation rate (ESR) and dehydration using the haematocrit levels. RESULTS: We included 75 females with a mean age of 15.2 years and 64% had a BMI Z score of <-2. The mean albumin and pre-albumin levels were 4.8 g/dL and 22.2 mg/dL, respectively, with 24% of the children having low pre-albumin and none having low albumin levels. The stepwise multiple regression for albumin identified ESR and haematocrit as significant predictors, which explained 14.8% of the variance. Age was the only significant predictor for pre-albumin, which explained 15.3% of the variance. CONCLUSION: Albumin, but not pre-albumin, levels were primarily predicted by low grade inflammation and hydration, but not by BMI. These markers should not be used to assess nutritional status in adolescents with RED. PMID- 26666980 TI - A Microperfusion and In-Bore Oxygenator System Designed for Magnetic Resonance Microscopy Studies on Living Tissue Explants. AB - Spectrometers now offer the field strengths necessary to visualize mammalian cells but were not designed to accommodate imaging of live tissues. As such, spectrometers pose significant challenges--the most evident of which are spatial limitations--to conducting experiments in living tissue. This limitation becomes problematic upon trying to employ commercial perfusion equipment which is bulky and--being designed almost exclusively for light microscopy or electrophysiology studies--seldom includes MR-compatibility as a design criterion. To overcome problems exclusive to ultra-high magnetic field environments with limited spatial access, we have designed microperfusion and in-bore oxygenation systems capable of interfacing with Bruker's series of micro surface-coils. These devices are designed for supporting cellular resolution imaging in MR studies of excised, living tissue. The combined system allows for precise control of both dissolved gas and pH levels in the perfusate thus demonstrating applicability for a wide range of tissue types. Its compactness, linear architecture, and MR-compatible material content are key design features intended to provide a versatile hardware interface compatible with any NMR spectrometer. Such attributes will ensure the microperfusion rig's continued utility as it may be used with a multitude of contemporary NMR systems in addition to those which are currently in development. PMID- 26666982 TI - Successful treatment of early-stage lower extremity lymphedema with side-to-end lymphovenous anastomosis with indocyanine green lymphography assisted. AB - PURPOSE: This study was to investigate intraoperative assessment of side-to-end lymphovenous anastomosis (LVA) with indocyanine green (ICG) and the correlation between its patency and surgical outcome. METHODS: LVA was applied to five patients with early-stage lower extremity lymphedema. Side-to-end anastomosis and then end-to-end anastomosis were created as a second alternative. Immediately after the anastomosis, ICG was used to confirm its patency. RESULTS: The mean number of anastomoses was 2.0 +/- 0.7, and the types of anastomoses were primarily side-to-end and secondarily end-to-end. The mean reduction rate was 63.8 +/- 20.2% after LVA at 10 +/- 6.4 months of follow-up. In all cases, the affected extremities became soft immediately after surgery, and no cellulitis episodes were observed. CONCLUSION: Side-to-end LVA can be an effective treatment for early-stage lower extremity lymphedema. ICG lymphodynamic assessment is useful not only in the preoperative identification of functional lymphatics but also in the intraoperative visualization of new drainage routes in LVA surgery. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:310-315, 2016. PMID- 26666983 TI - Laterality effects in the spinning dancer illusion: The viewing-from-above bias is only part of the story. AB - The 'silhouette illusion', representing the silhouette of a female dancer pirouetting about her vertical axis, is a bistable stimulus created by Japanese web designer Nobuyuki Kayahara. Although the dancer can be perceived as spinning either clockwise or counterclockwise, the clockwise rotation is usually preferred. Troje and McAdam (i-Perception, 2010, 1, 143) showed that this clockwise bias can be attributed to the tendency to assume a viewpoint from above rather than from below, given that the dancer is portrayed from a vantage point that is not perpendicular to the axis of rotation. Here, we tested whether another possible factor contributing to the observers' interpretation of this bistable stimulus might be the tendency to perceive movements of the right rather than the left foot. We confirmed both the viewing-from-above bias and our hypothesis. The bias to perceive movements of the right leg might be a generalization to lower limbs of a perceptual frequency effect already observed for upper limbs. Such a perceptual and attentional bias towards the right hand/foot could account for the greater ability to predict the outcome of sport actions when observing right- rather than left-limbed movements, and thus the left-handers' and left-footers' advantage observed in a variety of interactive sports. PMID- 26666981 TI - Clinical impact of the disposable ventouse iCup(r) versus a metallic vacuum cup: a multicenter randomized controlled trial. AB - BACKGROUND: Assisted vaginal delivery by vacuum extraction is frequent. Metallic resterilizible metallic vacuum cups have been routinely used in France. In the last few years a new disposable semi-soft vacuum extraction cup, the iCup, has been introduced. Our objective was to compare maternal and new-born outcomes between this disposable cup and the commonly used Drapier-Faure metallic cup. METHODS: This was a multicenter prospective randomized controlled open clinical trial performed in the maternity units of five university hospitals and one community hospital in France from October 2009 to February 2013. We included consecutive eligible women with a singleton gestation of at least 37 weeks who required vacuum assisted delivery. Women were randomized to vacuum extraction using the iCup or usual Drapier-Faure metallic cup. The primary outcome was a composite criterion including both the risk of cup dysfunction and the most frequent maternal and neonatal harms: the use of other instruments after attempted vacuum extraction, caesarean section after attempted vacuum extraction, three detachments of the cup, caput succedaneum, cephalohaematoma, episiotomy and perineal tears. RESULTS: 335 women were randomized to the disposable cup and 333 to extraction using the metallic cup. There was no significant difference between the two groups for the primary outcome. However, failed instrumental delivery was more frequent in the disposable cup group, mainly due to detachment: 35.6 % vs 7.1 %, p < 0.0001. Conversely, perineal tears were more frequent in the metallic cup group, especially third or fourth grade perineal tears: 1.7 % versus 5.0 %, p = 0.003. There were no significant differences between the two groups concerning post-partum haemorrhage, transfer to a neonatal intensive care unit (NICU) or serious adverse events. CONCLUSIONS: While the disposable cup had more detachments and extraction failures than the standard metallic cup, this innovative disposable device had the advantage of fewer perineal injuries. TRIAL REGISTRATION: www.clinicaltrials.gov : NCT01058200 on Jan. 27 2010. PMID- 26666984 TI - With or without rafts? Alternative views on cell membranes. AB - The fundamental mechanisms of protein and lipid organization at the plasma membrane have continued to engage researchers for decades. Among proposed models, one idea has been particularly successful which assumes that sterol-dependent nanoscopic phases of different lipid chain order compartmentalize proteins, thereby modulating protein functionality. This model of membrane rafts has sustainably sparked the fields of membrane biophysics and biology, and shifted membrane lipids into the spotlight of research; by now, rafts have become an integral part of our terminology to describe a variety of cell biological processes. But is the evidence clear enough to continue supporting a theoretical concept which has resisted direct proof by observation for nearly twenty years? In this essay, we revisit findings that gave rise to and substantiated the raft hypothesis, discuss its impact on recent studies, and present alternative mechanisms to account for plasma membrane heterogeneity. PMID- 26666985 TI - Construction of Metal-Ion-Free G-quadruplex-Hemin DNAzyme and Its Application in S1 Nuclease Detection. AB - In this work, a new kind of peroxidase-mimicking DNAzyme (G-quadruplex-hemin DNAzyme, G4-hemin) was constructed by using hemin-modified G-rich DNA (hemin-G DNA). Experimental results demonstrated that the G-rich DNA can form a G quadruplex structure by the inducement of terminally modified hemin, rendering the assembly of hemin and G-quadruplex structure spontaneously and efficiently. As a result, G-hemin revealed higher peroxidase activity than traditional G quadruplex/hemin DNAzyme (G4/hemin). Besides, different from G4/hemin, G4-hemin was constructed in one step without the participation of metal ions and adscititious hemin. Accordingly, the construction procedure was significantly simplified and the background signal from dissociative hemin was remarkably reduced. In a proof-of-concept trial, according to the colorimetric signals of G4 hemin, a novel biosensor for the detection of S1 nuclease activity was established, which provides a novel perspective for designing peroxidase mimicking DNAzyme-based biosensors. PMID- 26666986 TI - Diffusion behaviour of the acetaldehyde scavenger 2-aminobenzamide in polyethylene terephthalate for beverage bottles. AB - Polyethylene terephthalate (PET) bottles are widely used as packaging material for natural mineral water. However, trace levels of acetaldehyde can migrate into natural mineral water during the shelf life and might influence the taste of the PET bottled water. 2-Aminobenzamide is widely used during PET bottle production as a scavenging agent for acetaldehyde. The aim of this study was the determination of the migration kinetics of 2-aminobenzamide into natural mineral water as well as into 20% ethanol. From the migration kinetics, the diffusion coefficients of 2-aminobenzamide in PET at 23 and 40 degrees C were determined to be 4.2 * 10(-)(16) and 4.2 * 10(-)(15) cm(2) s(-1), respectively. The diffusion coefficient for 20% ethanol at 40 degrees C was determined to be 7.7 * 10(-)(15) cm(2) s(-1), which indicates that 20% ethanol is causing swelling of the PET polymer. From a comparison of migration values between 23 and 40 degrees C, acceleration factors of 9.7 when using water as contact medium and 18.1 for 20% ethanol as simulant can be derived for definition of appropriate accelerated test conditions at 40 degrees C. The European Union regulatory acceleration test based on 80 kJ mol(-1) as conservative activation energy overestimates the experimentally determined acceleration rates by a factor of 1.6 and 3.1, respectively. PMID- 26666987 TI - Evaluation of the mutagenic and genotoxic effects of the ALC67 thiazolidine compound in Salmonella strains and human lymphocytes in vitro. AB - ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4 carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities. PMID- 26666988 TI - Iron and carbon monoxide prevent degradation of plasmatic coagulation by thrombin like activity in rattlesnake venom. AB - Thousands suffer poisonous snake bite, often from defibrinogenating species annually. Three rattlesnake species in particular, the timber rattlesnake, Eastern diamondback rattlesnake, and Southern Pacific rattlesnake, cause clinically relevant hypofibrinogenemia via thrombin-like activity in their venom. It has been demonstrated that iron (Fe) and carbon monoxide (CO) change the ultrastructure of plasma thrombi and improve coagulation kinetics. Thus, the present investigation sought to determine if pretreatment of plasma with Fe and CO could attenuate venom-mediated catalysis of fibrinogen via thrombin-like activity. Human plasma was pretreated with ferric chloride (0-10 MUM) and CO releasing molecule-2 (0-100 MUM) prior to exposure to 2.5-10 MUg/ml of venom obtained from the aforementioned three species of rattlesnake. Coagulation kinetics were determined with thrombelastography. All three snake venoms degraded plasmatic coagulation kinetics to a significant extent, especially diminishing the speed of clot growth and strength. Pretreatment of plasma with Fe and CO completely abrogated the effects of all three venoms on coagulation kinetics. Further in vitro investigation of other pit viper venoms that possess thrombin like activity is indicated to see if there is significant conservation of venom enzymatic target recognition of specific amino acid sequences such that Fe and CO can reliably attenuate venom-mediated catalysis of fibrinogen. These data also serve as a rationale for future preclinical investigation. PMID- 26666989 TI - Glycogen phosphorylase inhibitors: a patent review (2013 - 2015). AB - INTRODUCTION: Control of glycemia is crucial in the treatment of type 2 diabetes complications. Glycogen phosphorylase (GP) releases glucose from the liver into the blood stream. Design of potent GP inhibitors is a therapeutic strategy in the context of type 2 diabetes. AREAS COVERED: Glucose-based inhibitors have found potential applications since they now reach low nanomolar Ki values. Another set of patents disclose cholic acid/7-aza-indole conjugates for targeted drug delivery to the liver. A series of benzazepinones have also been reported as potent GP inhibitors. In vitro data are reported for GP inhibition but the in vivo biological data at the cellular or animal levels are often missing, even though the literature reported for these molecules is also discussed. EXPERT OPINION: A structural analogy between glucose-based GP inhibitors and C glucosides targeting sodium glucose co-transporter 2 (SGLT2) is intriguing. Cholic acid/7-aza-indole conjugates are promising in vivo drug delivery systems to the liver. Benzazepinones were very recently described and no associated literature is available, making it very difficult to comment at present. While industry has slowed down on GP inhibitors design, academic groups are pursuing investigations and have provided potential drug candidates which will resuscitate the interest for GP, including its potential for targeting cancer. PMID- 26666991 TI - Influence of hydroxyapatite granule size, porosity, and crystallinity on tissue reaction in vivo. Part A: synthesis, characterization of the materials, and SEM analysis. AB - OBJECTIVE: The aim of this study was the synthesis and analysis of the tissue reaction to three different Hydroxyapatite (HA)-based bone substitute materials differing only in granule size, porosity, and crystallinity through an animal experimental model at 60 days. MATERIALS AND METHODS: Three different HA-based biomaterials were synthesized and characterized by X-ray diffraction, SEM, and EDS analysis, the resultant product was ground in three particle sizes: Group I (2000-4000 MUm), Group II (1000-2000 MUm), and Group III (600-1000 MUm). Critical size defects were created in both tibias of 15 rabbits. Four defects per rabbit for a total of 60 defects were grafted with the synthesized materials as follows: Group I (15 defects), Group II (15 defects), Group III (15 defects), and empty (15 defects control). After animals sacrifice at 60 days samples were obtained and processed for SEM and EDS evaluation of Ca/P ratios, elemental mapping was performed to determine the chemical degradation process and changes to medullary composition in all the four study groups. RESULTS: The tendency for the density was to increase with the increasing annealing temperature; in this way it was possible to observe that the sample that shows highest crystallinity and crystal size corresponding to that of group I. The SEM morphological examination showed that group III implant showed numerous resorption regions, group II implant presented an average resorption rate of all the implants. The group I displayed smoother surface features, in comparison with the other two implants. CONCLUSION: The data from this study show that changing the size, porosity, and crystallinity of one HA-based bone substitute material can influence the integration of the biomaterials within the implantation site and the new bone formation. PMID- 26666990 TI - Systematic analysis of the kalimantacin assembly line NRPS module using an adapted targeted mutagenesis approach. AB - Kalimantacin is an antimicrobial compound with strong antistaphylococcal activity that is produced by a hybrid trans-acyltransferase polyketide synthase/nonribosomal peptide synthetase system in Pseudomonas fluorescens BCCM_ID9359. We here present a systematic analysis of the substrate specificity of the glycine-incorporating adenylation domain from the kalimantacin biosynthetic assembly line by a targeted mutagenesis approach. The specificity conferring code was adapted for use in Pseudomonas and mutated adenylation domain active site sequences were introduced in the kalimantacin gene cluster, using a newly adapted ligation independent cloning method. Antimicrobial activity screens and LC-MS analyses revealed that the production of the kalimantacin analogues in the mutated strains was abolished. These results support the idea that further insight in the specificity of downstream domains in nonribosomal peptide synthetases and polyketide synthases is required to efficiently engineer these strains in vivo. PMID- 26666992 TI - Reduction of viable Enterococcus faecalis in human radicular dentin treated with 1% cetrimide and conventional intracanal medicaments. AB - AIM: The purpose of this study was to evaluate the viability of E. faecalis after a 14-day exposure to 1% cetrimide (CET), triantibiotic paste (i.e., metronidazole, minocycline, and ciprofloxacin), 2% chlorhexidine (CHX) gel, and calcium hydroxide (Ca[OH]2 ) in an infected dentine model. MATERIALS AND METHODS: A total of 75 roots of extracted uniradicular human teeth were chemomechanically prepared, sterilized, and infected for 21 days with E. faecalis. Samples were divided into five groups (n = 15) to apply intracanal medicaments, namely saline solution (negative control), 1% CET, triantibiotic paste (TRIA), 2% CHX gel, and Ca(OH)2 during 14 days. Dentine samples were collected and stained with the SYTO 9/propidium iodide technique (Live/Dead, Bacligth, Invitrogen, Eugene, OR, USA) for fluorescence microscopy to obtain the percentage of viable cells. Statistical analysis was performed using one-way analysis of variance followed by Tukey's multiple comparison test (P < 0.05). RESULTS: All experimental agents significantly reduced the percentage of viable E. faecalis when compared with the control group. In addition, the least cytotoxic medicament was Ca(OH)2 followed by CHX. There was no significant difference between 1% CET and TRIA (P = 0.98). CONCLUSION: Both 1% CET and TRIA significantly reduced the viability of E. faecalis in dentine of extracted teeth in comparison with 2% CHX gel and calcium hydroxide paste. Further laboratory and clinical investigations should be carried out to validate findings of the beneficial use of 1% CET as an intracanal medicament against E. faecalis. PMID- 26666993 TI - Cor a 14 is the superior serological marker for hazelnut allergy in children, independent of concomitant peanut allergy. AB - BACKGROUND: Hazelnut is the most frequent cause of tree nut allergy, but up to half of all children with hazelnut allergy additionally suffer from peanut allergy. Our aim was to identify diagnostic values of the most promising serological markers (Cor a 9 and Cor a 14) and to address the influence of concomitant peanut allergy and PR10 sensitization. METHOD: We included 155 children suspected of hazelnut allergy and challenged according to the guidelines. Concomitant allergy to peanuts was verified or ruled out by challenge. Skin prick test, s-IgE and CRD to hazelnut, peanut, PR10 and LPT protein families were measured using ImmunoCAP. RESULTS: Sixty-five children had a positive hazelnut challenge, and 60% of these also had a concomitant peanut allergy. Children allergic to hazelnut were sensitized to Cor a 9 and Cor a 14; peanut-allergic children were sensitized to Ara h 2. Sensitization to PR10 protein components was seen in 45% of all included children, irrelevant to allergy to peanut or hazelnut. A cut-off >0.72 kU/L of IgE towards Cor a 14 diagnosed 87% correctly, making Cor a 14 the superior serology marker. However, nine hazelnut-allergic children were primarily sensitized to Cor a 9. CONCLUSION: Concomitant peanut allergy is common in hazelnut-allergic children, but decision points as well as diagnostic values for Cor a 14 are not affected. We found three independent and well-characterized serotypes; hazelnut-allergic children were sensitized to Cor a 14, peanut-allergic children were sensitized to Ara h 2, and independently of this were children sensitized to birch pollen (Bet v 1). PMID- 26666995 TI - Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway. AB - AIM: Overwhelming oxidative stress is implicated as crucial in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Liraglutide, a well-established antidiabetes drug, was recently reported to ameliorate NAFLD with an elusive mechanism. We used a mouse model to examine whether liraglutide could ameliorate NAFLD and explored the possible mechanisms. METHODS: Twenty C57BL/6J mice were randomly treated with a normal-fat diet or high-fat diet for 16 weeks, then further distributed into four groups and subjected to s.c. injection of liraglutide or saline for 4 weeks. The growth/metabolism, oxidative stress, mitochondrial architecture and autophagy were assessed prospectively at the 20th week. RESULTS: High-fat diet inducement resulted in severe NAFLD while liraglutide treatment significantly reversed the trend, marked by reduced bodyweight, improved glucose tolerance and liver triglyceride composition. Reduced hepatic malondialdehyde level, increased mRNA and protein levels of CATALASE and MNSOD indicated liraglutide affected both the oxidative and antioxidative process to ameliorate oxidative stress. After liraglutide administration, the upregulated mRNA and protein levels of mitochondrial fission and fusion-related DRP1, OPA1 and respiratory chain-related COMPLEX1, UCP2 demonstrated the enhancement of mitochondrial architecture which may attenuate the generation of reactive oxygen species (ROS), while the diminished mRNA and protein level of P62 and increased levels of Beclin1 and LC3II/I ratio indicated the promoting autophagy, which probably contribute to the ROS elimination. Further, restored protein levels of Sirtuin1/Sirtuin3 and the downstream p-FOXO3a reveal the probable pathways of liraglutide acting on autophagy. CONCLUSION: Liraglutide diminishes oxidative stress by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a-LC3 pathway to ameliorate diet-induced NAFLD. PMID- 26666997 TI - Endoscopic Treatment of Early Biliary Complications in Liver Transplant Recipients. AB - BACKGROUND: The most common complications following liver transplantation (LTx) concern the biliary ducts. Potential early complications are biliary leaks and anastomotic strictures of the bile duct. The aim of this study was to evaluate the efficacy of endoscopic treatment of early biliary complications in liver transplant recipients after end-to-end biliary anastomosis. MATERIAL AND METHODS: From January 2011 to December 2013, 475 patients underwent LTx at our Department. There were 101 endoscopic procedures performed in total during this period, out of which 67 were related to biliary complications in 44 patients, while the remaining procedures were carried out due to gastrointestinal bleeding. We established a timeframe of up to 3 months postoperatively as the early biliary complication period. With the selected criteria we retrospectively analyzed medical records of 24 liver recipients who underwent endoscopic treatment due to early biliary complications. The outcome of endoscopic treatment was statistically analyzed and categorized as a technical and clinical success. RESULTS: During this period there were 38 endoscopic procedures in the analyzed group of patients treated due to early biliary complications. The results were: successful balloon dilation alone was performed in 2 patients with no further need of treatment, implantation of plastic stents was performed initially in 13 patients, but 7 patients required further stenting with larger caliber plastic stents (PS). Self-expandable metal stents (SEMS) were initially placed in 7 patients during this period overall. One patient was treated due to hemobilia. In 1 case endoscopic retrograde cholangiopancreatography (ERCP) was unfeasible and the patient required surgical intervention. In 1 case a PS was exchanged for an SEMS. Six patients with satisfactory cholangiography images had the stent removed during the second ERCP. CONCLUSIONS: In consideration of the stabilized rate of biliary complications following LTx, an advanced transplant center cannot function without an experienced endoscopist. For early biliary leaks and anastomotic strictures, ERCP is the primary treatment. PMID- 26666996 TI - Longitudinal association between preschool fussy eating and body composition at 6 years of age: The Generation R Study. AB - BACKGROUND: Children's fussy eating behavior has been related to both underweight and overweight in cross-sectional studies, but the direction of these associations and the relation with more detailed measures of body composition remains unclear. We aimed to examine whether fussy eating at age 4 years is longitudinally related to body mass index (BMI), fat mass index (FMI) and fat free mass index (FFMI) at 6 years of age. METHODS: This study was embedded in Generation R, a population-based, prospective cohort. Data were available for 4191 children. The Children's Eating Behaviour Questionnaire (CEBQ), administered at age 4 years, was used to derive a fussy eating profile. This profile is characterized by high scores on food avoidant scales and low scores on food approach scales. At age 6 years, height and weight were measured at our research center. Body fat and fat-free mass were measured using Dual-energy-X-ray absorptiometry. We used age- and sex-specific standard deviation scores (SDS) for all outcomes. RESULTS: After adjustment for confounders, the fussy eating profile was related to lower BMI-SDS (B = -0.37, 95% CI: -0.47;-0.26), lower FMI-SDS (B = -0.22, 95 % CI: -0.33;-0.12) and lower FFMI-SDS (B = -0.41, 95% CI: -0.54;-0.29). When adjusting for baseline BMI at 4 years, the fussy eating profile predicted a 0.11 lower BMI-SDS at age 6 (95% CI: -0.19;-0.04). This change in BMI was mainly due to a decrease in FFMI (B = -0.19, 95% CI: -0.29;-0.09). Fussy eaters also had a higher risk of becoming underweight than non-fussy eaters (OR = 2.28, 95% CI: 1.34;3.87). CONCLUSIONS: Our findings suggest that young fussy eaters are at risk of having a lower fat free mass and of becoming underweight over a 2-year period. This implies that fussy eaters may benefit from careful monitoring to prevent an adverse growth development. PMID- 26666998 TI - Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study. AB - BACKGROUND: Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-beta ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan. METHODS: Here, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group. RESULTS: The bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group. CONCLUSIONS: Our results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre treated group. TRIAL REGISTRATION: Current Controlled Trials NCT02156960. Registered 31 May 2014. PMID- 26666999 TI - Nanofibre Based Smart Pharmaceutical Scaffolds for Wound Repair and Regenerations. AB - Chronic wounds and ulcers are posing a devastating manifestation on the socioeconomic status across the globe along with the patient compliance. It reinforces a need for the development of successful alternative treatments for the chronic wound care and ulcer management practices. This review explores the progressive developments being made in the fabrication of electrospun nanofibrous scaffolds towards elimination of microbial infection from chronic wounds to accelerate the wound healing process. Functional three dimensional nanofibrous scaffolds produced by electrospinning have great potential in a wide spectrum of biomedical practices, such as tissue engineering, drug/gene delivery and wound dressing. Moreover, this review also highlights the materials and post modification methods, such as the functionaliation of electrospun nanofibrous scaffolds using growth factors, so that such smart and bioactive nanofibrous scaffolds could be made suitable for wound healing applications. PMID- 26667000 TI - The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders. AB - Many, if not all, chronic medical, neurodegenerative and neuroprogressive illnesses are characterised by chronic immune activation, oxidative and nitrosative stress (O&NS) and systemic inflammation. These factors, notably elevated pro-inflammatory cytokines, activate indoleamine 2,3-dioxygenase (IDO) leading to an upregulated tryptophan catabolite (TRYCAT) pathway of tryptophan degradation in the periphery and in the brain. In such conditions the TRYCAT pathway becomes the predominant system for tryptophan degradation in all body compartments. In this paper we review the pathways whereby TRYCATs may play a role in neuro-inflammatory and neuroprogressive disease. Thus chronic activation of the TRYCAT pathway leads to the production of a range of neuroactive, neuroprotective and neurotoxic TRYCATs. Some TRYCATs such as quinolinic acid act as potent neurotoxins which inhibit ATP production by mitochondria, provoke increases in O&NS, disrupt neuron glial communication and blood brain barrier integrity, induce apoptosis of glial cells, directly damage neurons and function as a N-methyl D-aspartate (NMDA) receptor agonist. Other TRYCATs such as kynurenic acid function as antagonists of NMDA, alpha- amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid and kainate receptors and act to regulate levels of glutamate and dopamine. The neuroprotective functions of this TRYCAT are likely exercised via engagement with alpha7 nicotinic acetylcholine and aryl hydrocarbon receptors but the neuroprotective effects stemming from elevated kynurenic acid levels come at the price of severely compromised neurocognitive function and emotional processing. Other TRYCATS also possess neurotoxic or neuroprotective properties via pro-oxidant and antioxidant effects. Here we discuss the involvement of the abovementioned TRYCAT pathways in schizophrenia, Alzheimer's disease and chronic fatigue syndrome. PMID- 26667001 TI - Tryptophan Metabolites and Their Impact on Multiple Sclerosis Progression. AB - Accumulating evidence demonstrates involvement of tryptophan metabolites and in particular activation of the kynurenine pathway (KP) in neurocognitive disorders under CNS inflammatory conditions. The KP is involved in several brain-associated disorders including Parkinson's disease, AIDS dementia, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, schizophrenia, and brain tumors. Our review is an attempt to address any relevant association between dysregulation of KP and multiple sclerosis (MS), an inflammatory CNS disorder that ultimately leads to demyelinated brain areas and severe neurological deficits. Modulation of KP is a new topic for the field of MS and warrants further research. The availability of potential KP modulators approved for MS may shed some light into the therapeutic potential of KP antagonists for the treatment of MS patients. PMID- 26667002 TI - Platypnea-Orthodeoxia in Patients on Hemodialysis: A New Approach to Its Pathophysiology and Implications for Treatment. AB - Platypnea-orthodeoxia is a poorly understood clinical syndrome resulting in dyspnea and hypoxemia in the upright position, which diminishes with recumbency. Recognition of the disease is limited by its low prevalence and decreased awareness among clinicians. However, understanding the disease, its pathophysiology, its clinical presentation, and the possible therapeutic options is vital in the management of these patients. Here, we present 2 cases of platypnea- orthodeoxia where oxygen saturations worsened with hemodialysis. After highlighting the common features in the clinical pattern of each patient, we present a pressure-mediated pathophysiologic mechanism (in contrast to a previously reported morphologically based hypothesis) to explain the characteristic effects of hemodialysis on hypoxia in platypnea-orthodeoxia. We present a novel diagnostic approach using balloon occlusion testing when the diagnosis is unclear and illustrate how treatments can be tailored to the comorbidities of a specific patient. PMID- 26667003 TI - Erythema nodosum as a result of estrogen patch therapy for prostate cancer: a case report. AB - INTRODUCTION: Erythema nodosum is often associated with a distressing symptomatology, including painful subcutaneous nodules, polyarthropathy, and significant fatigue. Whilst it is a well-documented side-effect of estrogen therapy in females, we describe what we believe to be the first report in the literature of erythema nodosum as a result of estrogen therapy in a male. CASE PRESENTATION: A 64-year-old Afro-Caribbean man with locally advanced carcinoma of the prostate agreed to participate in a randomized controlled trial comparing estrogen patches with luteinizing hormone-releasing hormone analogs to achieve androgen deprivation, and was allocated to the group receiving estrogen patches. One month later he presented with tender lesions on his shins and painful swelling of his ankles, wrists, and left shoulder. This was followed by progressive severe fatigue that required hospital admission, where he was diagnosed with erythema nodosum by a rheumatologist. Two months after discontinuing the estrogen patches the erythema nodosum, and associated symptoms, had fully resolved, and to date he remains well with no further recurrence. CONCLUSION: Trial results may establish transdermal estrogen as an alternative to luteinizing hormone-releasing hormone analogs in the management of prostate cancer, and has already been established as a therapy for male to female transsexuals. It is essential to record the toxicity profile of transdermal estrogen in men to ensure accurate safety information. This case report highlights a previously undocumented toxicity of estrogen therapy in men, of which oncologists, urologists, and endocrinologists need to be aware. Rheumatologists and dermatologists should add estrogen therapy to their differential diagnosis of men presenting with erythema nodosum. PMID- 26667004 TI - Is Performance-Based Progress Testing in Psychiatry Feasible? AB - OBJECTIVE: The aim of this study was to explore if competency-based progress tests for postgraduate psychiatry are reliable, if they are able to discriminate trainees at different levels of training, and if they are able to demonstrate improvement of trainees' skills from 3 years of data. METHODS: Psychiatry trainees in the North Western Deanery, UK, were invited to participate in the annual progress test. The progress test simulated the Clinical Assessment of Skills and Competencies (CASC) exam, the final postgraduate examination for psychiatry trainees. The sum of global scores from all stations for each candidate was used for statistical analysis. Cronbach's alpha was used to calculate the interstation reliability. Analysis of variance (ANOVA) was used to explore if the progress test could discriminate between the three levels of trainees each year. Student's t test was used to explore if there was improvement and development of skills as a cohort progressed; ANOVA was used for the cohort with 3 years of data. RESULTS: The progress test is more likely to be reliable (alpha >= 0.8) when 12 stations are used. ANOVA revealed significantly improved scores with increasing level of seniority in 2012, with a mean total score increasing from 23.1 to 31.3 (p = 0.008) and 36.9 to 46.6 in 2013 (p = 0.004). In 2014, this effect was not observed, with a mean decreasing from 42.4 to 41.3. Over time, two cohorts demonstrated improving mean scores with Student's t tests from 26.4 to 32.4 (p = 0.01) and 26.9 to 42.6 (p = 0.01). The third cohort did not demonstrate a difference over time, with mean scores 23.1, 27.6, and 25.9 over 3 years. CONCLUSIONS: It is not conclusive if the progress test can accurately distinguish between trainee seniority or assess progress over time; possible explanations for non-significant results and further avenues of enquiry are discussed. PMID- 26667005 TI - Reformulating Suicide Risk Formulation: From Prediction to Prevention. AB - Psychiatrists-in-training typically learn that assessments of suicide risk should culminate in a probability judgment expressed as "low," "moderate," or "high." This way of formulating risk has predominated in psychiatric education and practice, despite little evidence for its validity, reliability, or utility. We present a model for teaching and communicating suicide risk assessments without categorical predictions. Instead, we propose risk formulations which synthesize data into four distinct judgments to directly inform intervention plans: (1) risk status (the patient's risk relative to a specified subpopulation), (2) risk state (the patient's risk compared to baseline or other specified time points), (3) available resources from which the patient can draw in crisis, and (4) foreseeable changes that may exacerbate risk. An example case illustrates the conceptual shift from a predictive to a preventive formulation, and we outline steps taken to implement the model in an academic psychiatry setting. Our goal is to inform educational leaders, as well as individual educators, who can together cast a prevention-oriented vision in their academic programs. PMID- 26667006 TI - JAMA and Jammies: The Work-Life Balance of an Intern. PMID- 26667007 TI - Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus. AB - This study examined whether xanthohumol, a hop-derived prenylated flavonoid present in beer, affects glutamate release in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), xanthohumol inhibited the release of 4-aminopyridine (4-AP)-evoked glutamate and the elevation of cytosolic Ca(2+) concentration, whereas it had no effect on 4-AP-mediated depolarization. The inhibitory effect of xanthohumol on the evoked glutamate release was prevented by removing extracellular Ca(2+), using the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker omega-CgTX MVIIC, the calmodulin antagonists W7 and calmidazolium, and the protein kinase A inhibitor H89; however, no such effect was observed when the G-protein inhibitor N-ethylmaleimide was used. In addition, immunocytochemical data demonstrated that GABAA receptors are present in the hippocampal synaptosomes and that the xanthohumol effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Furthermore, in slice preparations, xanthohumol reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude. We conclude that xanthohumol acts at GABAA receptors present in the hippocampal nerve terminals to decrease the Ca(2+) influx through N- and P/Q-type Ca(2+) channels, which subsequently suppresses the Ca(2+)-calmodulin/PKA cascade to decrease the evoked glutamate release. PMID- 26667008 TI - Profilometry: A new statistical framework for the characterization of white matter pathways, with application to multiple sclerosis. AB - AIMS: describe a new "profilometry" framework for the multimetric analysis of white matter tracts, and demonstrate its application to multiple sclerosis (MS) with radial diffusivity (RD) and myelin water fraction (MWF). METHODS: A cohort of 15 normal controls (NC) and 141 MS patients were imaged with T1, T2 FLAIR, T2 relaxometry and diffusion MRI (dMRI) sequences. T1 and T2 FLAIR allowed for the identification of patients having lesion(s) on the tracts studied, with a special focus on the forceps minor. T2 relaxometry provided MWF maps, while dMRI data yielded RD maps and the tractography required to compute MWF and RD tract profiles. The statistical framework combined a multivariate analysis of covariance (MANCOVA) and a linear discriminant analysis (LDA) both accounting for age and gender, with multiple comparison corrections. RESULTS: In the single-case case study the profilometry visualization showed a clear departure of MWF and RD from the NC normative data at the lesion location(s). Group comparison from MANCOVA demonstrated significant differences at lesion locations, and a significant age effect in several tracts. The follow-up LDA analysis suggested MWF better discriminates groups than RD. DISCUSSION AND CONCLUSION: While progress has been made in both tract-profiling and metrics for white matter characterization, no single framework for a joint analysis of multimodality tract profiles accounting for age and gender is known to exist. The profilometry analysis and visualization appears to be a promising method to compare groups using a single score from MANCOVA while assessing the contribution of each metric with LDA. PMID- 26667009 TI - Age-dependent motor unit remodelling in human limb muscles. AB - Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements. PMID- 26667011 TI - Influence of religious organisations' statements on compliance with a smoke-free law in Bogor, Indonesia: a qualitative study. AB - OBJECTIVE: To explore the Bogor public's perspective on Muslim organisations' pronouncements against smoking and the effect of these pronouncements on compliance with a new smoke-free law in the context of a prosmoking social norm. DESIGN: Semistructured focus group discussions were conducted, transcribed, coded using ATLAS.ti software, and analysed using thematic content analysis. Photo elicitation was also used during the focus groups. SETTING: Bogor, Indonesia. PARTICIPANTS: 11 focus groups (n=89), stratified by age, gender and smoking status, with members of the public (46 male, 43 female, ages 18-50). RESULTS: There was limited knowledge of and compliance with both the smoke-free law and the religious pronouncements. In most of the focus groups, smoking was described as a discouraged, but not forbidden, behaviour for Muslims. Participants described the decision of whether to follow the religious pronouncements in the context of individual choice. Some participants felt religious organisations lacked credibility to speak against smoking because many religious leaders themselves smoke. However, some non-smokers said their religion reinforced their non-smoking behaviour and some participants stated it would be useful for religious leaders to speak more about the smoke-free law. CONCLUSIONS: Religious organisations' pronouncements appear to have had a small effect, primarily in supporting the position of non-smokers not to smoke. Participants, including smokers, said their religious leaders should be involved in supporting the smoke free law. These findings suggest there is potential for the tobacco control community to partner with sympathetic local Muslim leaders to promote common goals of reducing smoking and public smoke exposure. Muslim leaders' views on smoking would be perceived as more credible if they themselves followed the smoke free law. Additionally, public health messaging that includes religious themes could be piloted and tested for effectiveness. These findings may also inform similar efforts in other Muslim cities implementing smoke-free laws. PMID- 26667010 TI - The impact of obesity on skeletal muscle strength and structure through adolescence to old age. AB - Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance limitations. The consensus is that obese individuals, regardless of age, have a greater absolute maximum muscle strength compared to non-obese persons, suggesting that increased adiposity acts as a chronic overload stimulus on the antigravity muscles (e.g., quadriceps and calf), thus increasing muscle size and strength. However, when maximum muscular strength is normalised to body mass, obese individuals appear weaker. This relative weakness may be caused by reduced mobility, neural adaptations and changes in muscle morphology. Discrepancies in the literature remain for maximal strength normalised to muscle mass (muscle quality) and can potentially be explained through accounting for the measurement protocol contributing to muscle strength capacity that need to be explored in more depth such as antagonist muscle co activation, muscle architecture, a criterion valid measurement of muscle size and an accurate measurement of physical activity levels. Current evidence demonstrating the effect of obesity on muscle quality is limited. These factors not being recorded in some of the existing literature suggest a potential underestimation of muscle force either in terms of absolute force production or relative to muscle mass; thus the true effect of obesity upon skeletal muscle size, structure and function, including any interactions with ageing effects, remains to be elucidated. PMID- 26667012 TI - Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. AB - OBJECTIVES: To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. DESIGN: Retrospective cohort study using an anonymised electronic health record case register. SETTING: South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. PARTICIPANTS: 21,012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. EXPOSURE: Prior antidepressant therapy recorded in electronic health records. MAIN OUTCOME MEASURE: Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. METHODS: Multivariable Cox regression analysis with age and gender as covariates. RESULTS: The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). CONCLUSIONS: In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression. PMID- 26667013 TI - Prevalence and risk factors of retinopathy in patients with or without metabolic syndrome: a population-based study in Shenyang. AB - OBJECTIVE: To investigate the relationship between metabolic syndrome (MS) and the prevalence of retinopathy. DESIGN: A cross-sectional study was carried out from August 2013 to September 2014 in Fengyutan Sub-District. PRIMARY AND SECONDARY OUTCOME MEASURES: A total of 1163 eligible participants attended. All the participants were subjected to stereo fundus photography to detect retinopathy. The discrepancy of prevalence of retinopathy in different participants was described. RESULTS: The prevalence of retinopathy was 9.64% in patients with MS and 3.91% in patients without MS. A higher prevalence of retinopathy with proliferative diabetic retinopathy was found in patients with MS. In multiple logistic regression analysis, independent risk factors for any retinopathy in patients with MS were longer diabetes duration (OR 1.07; 95% CI 1.04 to 1.10, per year increase), higher systolic blood pressure (SBP) (OR 1.16; 95% CI 1.09 to 1.29, per 10 mm Hg increase), higher diastolic blood pressure (DBP) (OR 1.24; 95% CI 1.12 to 1.35, per 10 mm Hg increase), higher fasting plasma glucose (OR 1.07; 95% CI 1.02 to 1.11, per 10 mg/dL increase), higher 2 h postprandial plasma glucose (OR 1.17; 95% CI 1.12 to 1.21, per 10 mg/dL increase), and higher haemoglobin A1c (HbA1c) (OR 1.23; 95% CI 1.13 to 1.34, per % increase). Similar independent risk factors, except for DBP, were found for any retinopathy in patients without MS. CONCLUSIONS: The presence of MS components, hyperglycaemia (fasting glucose and HbA1c) and hypertension (SBP and DBP), are significantly associated with the prevalence of retinopathy. PMID- 26667014 TI - Associations between stress disorders and cardiovascular disease events in the Danish population. AB - OBJECTIVES: Post-traumatic stress disorder (PTSD) is a well-documented risk factor for cardiovascular disease (CVD). However, it is unknown whether another common stress disorder-adjustment disorder--is also associated with an increased risk of CVD and whether gender modifies these associations. The aim of this study was to examine the overall and gender-stratified associations between PTSD and adjustment disorder and 4 CVD events. DESIGN: Prospective cohort study utilising Danish national registry data. SETTING: The general population of Denmark. PARTICIPANTS: PTSD (n=4724) and adjustment disorder (n=64,855) cohorts compared with the general population of Denmark from 1995 to 2011. PRIMARY OUTCOME MEASURES: CVD events including myocardial infarction (MI), stroke, ischaemic stroke and venous thromboembolism (VTE). Standardised incidence rates and 95% CIs were calculated. RESULTS: Associations were found between PTSD and all 4 CVD events ranging from 1.5 (95% CI 1.1 to 1.9) for MI to 2.1 (95% CI 1.7 to 2.7) for VTE. Associations that were similar in magnitude were also found for adjustment disorder and all 4 CVD events: 1.5 (95% CI 1.4 to 1.6) for MI to 1.9 (95% CI 1.8 to 2.0) for VTE. No gender differences were noted. CONCLUSIONS: By expanding beyond PTSD and examining a second stress disorder-adjustment disorder-this study provides evidence that stress-related psychopathology is associated with CVD events. Further, limited evidence of gender differences in associations for either of the stress disorders and CVD was found. PMID- 26667015 TI - Cancer treatment decision-making processes for older patients with complex needs: a qualitative study. AB - OBJECTIVES: Although older people can experience complex health and social care needs alongside a primary cancer diagnosis, little is understood about how cancer treatment decisions are made for this population. This study aimed to investigate how cancer treatment decisions are formulated for older people with complex health and social care needs and the factors that shape these processes. DESIGN: Qualitative study involving semistructured interviews and non-participant observations. Framework approach used for data analysis. SETTING: Breast and colorectal cancer services in five English NHS hospital trusts. PARTICIPANTS: Interviews: purposive sample of 22 clinicians directly involved in a face-to-face clinical role with patients regarding cancer treatment and care, maximising variation across clinical roles, tumour types and trusts. OBSERVATIONS: purposive sample of five cancer multidisciplinary meetings, maximising variation across location, team size and tumour type. RESULTS: The initial stages of cancer treatment decision-making are team-based, medically dominated and focused on the cancer. For patients with complex health and social care needs that extend beyond cancer pathology, later and less visible stages in the decision-making process are more haphazard and may result in less effective and workable treatment plans, as individual clinicians struggle to devise and deliver these plans without breaching time-based targets. CONCLUSIONS: Service targets that focus resources solely on the presenting disease can disadvantage older patients with complex health and social care needs that extend beyond this primary diagnosis. Care should be taken to ensure time-based targets do not disincentivise thorough and timely assessment that can lead to the formulation of treatment plans tailored to individual needs and circumstances. PMID- 26667016 TI - Evaluation of chemotherapeutic sequelae and quality of life in survivors of malignant sacrococcygeal teratoma. AB - PURPOSE: The impact of chemotherapeutic sequelae on long-term quality of life (QoL) for survivors of malignant sacrococcygeal teratoma (SCT) is unknown. The incidence of chemotherapeutic toxicity in patients treated for malignant SCT and possible effects on the QoL were analyzed. METHODS: Retrospective chart review of patients >=18 years treated for SCT in the Netherlands was performed. Present QoL was evaluated using the SF-36 questionnaire. The results of survivors of malignant SCT were compared to those of patients treated for benign SCT. RESULTS: Fifty-one of 76 traceable patients consented to participate. The results of 47 (92.2 %), 9 men and 38 women (median age 25.4 years, range 18.3-41.2), were analyzed. Eleven had been treated for malignancy; 63.6 % suffered from at least one chemotherapeutic sequel with hearing loss as the most common one. Results for both groups were similar on all but one SF-36 subcategory; those treated for malignant tumor scored significantly lower on the subcategory physical functioning (p = 0.02). CONCLUSION: Despite the high incidence of chemotherapeutic sequelae among survivors of malignant SCT, their QoL does not differ from that of those treated for benign SCT. Even though their physical functioning is restricted, daily activities and psychosocial functioning of survivors of malignant SCT are not restricted. PMID- 26667017 TI - Chimeric transcripts resulting from complex duplications in chromosome Xq28. AB - Gene fusions have been observed in somatic alterations in cancer and in schizophrenia. However, the underlying mechanism(s) for their formation are poorly understood. We experimentally demonstrated the expression of splicing variants of in silico predicted chimeric genes F8/CSAG1 and BCAP31/TEX28 in two individuals with de novo complex genomic rearrangements of Xq28; F8/CSAG1 includes exonization of an ERVL-MaLR intronic repetitive element. We provide evidence that replicative repair may contribute to exon shuffling processes and diversify the repertoire of expressed transcripts. PMID- 26667018 TI - SKAP, an outer kinetochore protein, is required for mouse germ cell development. AB - In sexually reproducing organisms, accurate gametogenesis is crucial for the transmission of genetic material from one generation to the next. This requires the faithful segregation of chromosomes during mitotic and meiotic divisions. One of the main players in this process is the kinetochore, a large multi-protein complex that forms at the interface of centromeres and microtubules. Here, we analyzed the expression profile and function of small kinetochore-associated protein (SKAP) in the mouse. We found that two distinct SKAP isoforms are specifically expressed in the germline: a smaller isoform, which is detected in spermatogonia and spermatocytes and localized in the outer mitotic and meiotic kinetochores from metaphase to telophase, and a larger isoform, which is expressed in the cytoplasm of elongating spermatids. We generated SKAP-deficient mice and found that testis size and sperm production were severely reduced in mutant males. This phenotype was partially caused by defects during spermatogonia proliferation before entry into meiosis. We conclude that mouse SKAP, while being dispensable for somatic cell divisions, has an important role in the successful outcome of male gametogenesis. In germ cells, analogous to what has been suggested in studies using immortalized cells, SKAP most likely stabilizes the interaction between kinetochores and microtubules, where it might be needed as an extra safeguard to ensure the correct segregation of mitotic and meiotic chromosomes. PMID- 26667019 TI - Intracellular chloride concentration of the mouse vomeronasal neuron. AB - BACKGROUND: The vomeronasal organ (VNO) is specialized in detecting pheromone and heterospecific cues in the environment. Recent studies demonstrate the involvement of multiple ion channels in VNO signal transduction, including the calcium-activated chloride channels (CACCs). Opening of CACCs appears to result in activation of VNO neuron through outflow of Cl(-) ions. However, the intracellular Cl(-) concentration remains undetermined. RESULTS: We used the chloride ion quenching dye, MQAE, to measure the intracellular Cl(-) concentration of VNO neuron in live VNO slices. The resting Cl(-) concentration in the VNO neurons is measured at 84.73 mM. Urine activation of the VNO neurons causes a drop in Cl(-) concentration, consistent with the notion of an efflux of Cl(-) to depolarize the cells. Similar observation is made for VNO neurons from mice with deletion of the transient receptor potential canonical channel 2 (TRPC2), which have a resting Cl(-) concentrations at 81 mM. CONCLUSIONS: The VNO neurons rest at high intracellular Cl(-) concentration, which can lead to depolarization of the cell when chloride channels open. These results also provide additional support of TRPC2-independent pathway of VNO activation. PMID- 26667020 TI - Two-hierarchical nonnegative matrix factorization distinguishing the fluorescent targets from autofluorescence for fluorescence imaging. AB - BACKGROUND: Nonnegative matrix factorization (NMF) has been used in blind fluorescence unmixing for multispectral in-vivo fluorescence imaging, which decomposes a mixed source data into a set of constituent fluorescence spectra and corresponding concentrations. However, most classical NMF algorithms have ill convergence problems and they always fail to unmix multiple fluorescent targets from background autofluorescence for the sparse acquisition of multispectral fluorescence imaging, which introduces incomplete measurements and severe discontinuities in multispectral fluorescence emissions across the multiple spectral bands. METHODS: Observing the spatial distinction between the diffusive autofluorescence and the sparse fluorescent targets, we propose to separate the mixed sparse multispectral data into equality constrained two-hierarchical updating within NMF framework by dividing the concentration matrix of entire endmembers into two hierarchies: the fluorescence targets and the background autofluorescence. Specifically, when updating concentrations of multiple fluorescent targets in the two-hierarchical NMF, we assume that the concentration of autofluorescence is fixed and known, and vice versa. Furthermore, a sparsity constraint is imposed on the concentration matrix components of fluorescence targets only. RESULTS: Synthetic data sets, in vivo fluorescence imaging data are employed to demonstrate and validate the performance of our approach. The proposed algorithm can achieve more satisfying results of spectral unmixing and autofluorescence removal compared to other state-of-the-art methods, especially for the sparse multispectral fluorescence imaging. CONCLUSIONS: The proposed algorithm can successfully tackle the sparse acquisition and ill-posed problems in the NMF-based fluorescence unmixing through equality constraint along with partial sparsity constraint during two-hierarchical NMF optimization, at which fixing sparsity constrained target fluorescence can make the update of autofluorescence as accurate as possible and vice versa. PMID- 26667023 TI - Physician spending and risk of malpractice claims: defensive medicine may not be as common as we think. PMID- 26667022 TI - Intertumor heterogeneity in vascularity and invasiveness of artificial melanoma brain metastases. AB - BACKGROUND: Patients diagnosed with melanoma brain metastases have few treatment options and poor prognosis, and improved treatment strategies for these patients require detailed understanding of the underlying pathobiology. In this investigation we studied the vascularity and invasiveness of artificial brain metastases established from four human melanoma cell lines. METHODS: A-07, D-12, R-18, and U-25 cells transfected with GFP were injected intracerebrally and intra arterially in nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or by histological examination. Expression and secretion of factors involved in angiogenesis and invasion were assessed by quantitative PCR, ELISA, and immunohistochemistry. RESULTS: The melanoma cells grew preferentially in the meninges and ventricles after intracerebral and intra arterial injection. Intertumor heterogeneity in the aggressiveness of meningeal tumors reflected differences in angiogenic activity and expression of vascular endothelial growth factor A (VEGF-A) and interleukin 8 (IL-8). In contrast, growth and invasion of the brain parenchyma relied primarily on vascular co option. The cell lines showed different patterns of invasion from meninges to the scull and from meninges to the brain parenchyma, and these differences were associated with differences in expression of the matrix metalloproteinases MMP-2 and MMP-9. Furthermore, the melanoma cells produced multiple brain lesions after intracerebral implantation by using the meningeal linings of the brain as transport routes. CONCLUSIONS: The melanoma cell lines showed different growth patterns in the brain, and these differences were associated with differences in expression of the angiogenic factors VEGF-A and IL-8 and the matrix metalloproteinases MMP-2 and MMP-9. PMID- 26667025 TI - Preliminary Examination of the Interpersonal Psychological Theory of Suicide in an Adolescent Clinical Sample. AB - This study offers a preliminary examination of the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner 2005) in an adolescent clinical sample. The IPTS offers a nuanced framework that has many conceptual and practical merits. Although this theory has a growing base of evidence among adults, it has yet to be tested in adolescents using direct measures of its central constructs. Participants were 147 adolescents (76.2 % girls) on an inpatient psychiatric unit, who completed measures of key IPTS constructs of thwarted belongingness, perceived burdensomeness, acquired capability for suicide, as well as depression severity, hopelessness, and severity of suicidal symptoms. Our findings were largely consistent with hypotheses derived from the IPTS: perceived burdensomeness, and at a marginal level, thwarted belongingness, were independently associated with current suicidal ideation. The thwarted belongingness by perceived burdensomeness interaction marginally distinguished between adolescents with passive and active suicidal ideation. Acquired capability for suicide was associated with recent suicidal intent. Examination of all three IPTS constructs simultaneously revealed main effects of each construct (with a marginal effect of thwarted belongingness), and interaction effects for thwarted belongingness by perceived burdensomeness, and thwarted belongingness by perceived burdensomeness by acquired capability for suicide in association with suicidal symptom severity. Sex, age, depression severity, and hopelessness were controlled in all analyses. This study offers strong, albeit preliminary, support of the IPTS in a clinical adolescent sample. Assessment of IPTS constructs may be useful in determining persistent risk for suicide attempt. Prospective tests of the theory, and extensions to intervention and prevention should be considered in future IPTS research. PMID- 26667026 TI - Permissive Parenting, Deviant Peer Affiliations, and Delinquent Behavior in Adolescence: the Moderating Role of Sympathetic Nervous System Reactivity. AB - The present study examined two measures of sympathetic nervous system (SNS) activity as moderators of the indirect path from permissive parenting to deviant peer affiliations to delinquency among a community sample of adolescents. Participants included 252 adolescents (M = 15.79 years; 53 % boys; 66 % European American, 34 % African American). A multi-method design was employed to address the research questions. Two indicators of SNS reactivity, skin conductance level reactivity (SCLR) and cardiac pre-ejection period reactivity (PEPR) were examined. SNS activity was measured during a baseline period and a problem solving task (star-tracing); reactivity was computed as the difference between the task and baseline periods. Adolescents reported on permissive parenting, deviant peer affiliations, externalizing behaviors, and substance use (alcohol, marijuana). Analyses revealed indirect effects between permissive parenting and delinquency via affiliation with deviant peers. Additionally, links between permissive parenting to affiliation with deviant peers and affiliation with deviant peers to delinquency was moderated by SNS reactivity. Less SNS reactivity (less PEPR and/or less SCLR) were risk factors for externalizing problems and alcohol use. Findings highlight the moderating role of SNS reactivity in parenting and peer pathways that may contribute to adolescent delinquency and point to possibilities of targeted interventions for vulnerable youth. PMID- 26667027 TI - Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort. AB - PURPOSE: Environmental phthalate exposure has been associated with attention deficit disorders in children. We hypothesized that in children treated in the pediatric intensive care unit (PICU), circulating phthalates leaching from indwelling medical devices contribute to their long-term attention deficit. METHODS: Circulating plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were quantified in 100 healthy children and 449 children who had been treated in PICU and were neurocognitively tested 4 years later. In a development patient cohort (N = 228), a multivariable bootstrap study identified stable thresholds of exposure to circulating DEHP metabolites above which there was an independent association with worse neurocognitive outcome. Subsequently, in a second patient cohort (N = 221), the observed independent associations were validated. RESULTS: Plasma concentrations of DEHP metabolites, which were virtually undetectable [0.029 (0.027-0.031) umol/l] in healthy children, were 4.41 (3.76-5.06) umol/l in critically ill children upon PICU admission (P < 0.001). Plasma DEHP metabolite concentrations decreased rapidly but remained 18 times higher until PICU discharge (P < 0.001). After adjusting for baseline risk factors and duration of PICU stay, and further for PICU complications and treatments, exceeding the potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with the attention deficit (all P <= 0.008) and impaired motor coordination (all P <= 0.02). The association with the attention deficit was confirmed in the validation cohort (all P <= 0.01). This phthalate exposure effect explained half of the attention deficit in post-PICU patients. CONCLUSIONS: Iatrogenic exposure to DEHP metabolites during intensive care was independently and robustly associated with the important attention deficit observed in children 4 years after critical illness. Clinicaltrials.gov identifier: NCT00214916. PMID- 26667028 TI - What do we treat when we treat ARDS? PMID- 26667029 TI - Algorithm development and the clinical and economic burden of Cushing's disease in a large US health plan database. AB - PURPOSE: This study aimed to develop an algorithm to identify patients with CD, and quantify the clinical and economic burden that patients with CD face compared to CD-free controls. METHODS: A retrospective cohort study of CD patients was conducted in a large US commercial health plan database between 1/1/2007 and 12/31/2011. A control group with no evidence of CD during the same time was matched 1:3 based on demographics. Comorbidity rates were compared using Poisson and health care costs were compared using robust variance estimation. RESULTS: A case-finding algorithm identified 877 CD patients, who were matched to 2631 CD free controls. The age and sex distribution of the selected population matched the known epidemiology of CD. CD patients were found to have comorbidity rates that were two to five times higher and health care costs that were four to seven times higher than CD-free controls. CONCLUSION: An algorithm based on eight pituitary conditions and procedures appeared to identify CD patients in a claims database without a unique diagnosis code. Young CD patients had high rates of comorbidities that are more commonly observed in an older population (e.g., diabetes, hypertension, and cardiovascular disease). Observed health care costs were also high for CD patients compared to CD-free controls, but may have been even higher if the sample had included healthier controls with no health care use as well. Earlier diagnosis, improved surgery success rates, and better treatments may all help to reduce the chronic comorbidity and high health care costs associated with CD. PMID- 26667030 TI - Do Working Hours and Type of Work Affect Obesity in South Korean Female Workers? Analysis of the Korean Community Health Survey. AB - BACKGROUND: The prevalence of obesity and the female labor participation rate have been rapidly increasing in South Korea. To examine the relationship between these factors, we investigated the association between timing and type of work and obesity in the Korean female working population. METHODS: Data collected by the 2008 Community Health Survey (CHS) were analyzed using a complex, stratified, multistage, probability cluster sampling method. Descriptive analysis of relevant variables was performed using the chi-square test, and work-related variables by work type were identified using multivariate logistic regression. The relationship between long working hours, night/shift work, and body-mass index in female workers and explanatory, stratifying, and dependent variables and covariates was analyzed using multiple logistic regression models. RESULTS: A total of 42,234 CHS participants were eligible for study inclusion. Among both manual and nonmanual workers, working less than 40 (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI] 1.07-1.31 and aOR 1.29; 95% CI 1.09-0.52, respectively) or more than 60 (aOR 1.18, 95% CI 1.06-1.30 and aOR 1.28, 95% CI 1.04-1.57, respectively) hours per week was significantly associated with obesity after controlling for covariates. However, working type (day or night/shift) was significantly associated with obesity only in nonmanual workers (aOR 1.20, 95% CI 1.01-1.42). When we controlled working type in the model, manual workers who work more than 60 hours show higher likelihood of being obese (OR 1.10, 95% CI 1.02 1.18). CONCLUSION: Working fewer (<40) or more than (>60) hours per week is significantly associated with obesity in the Korean female working population, regardless of the type of work. The type of work (day vs. night/shift work) was significantly associated with obesity only in only nonmanual workers. PMID- 26667031 TI - Origins and recent radiation of Brazilian Eupatorieae (Asteraceae) in the eastern Cerrado and Atlantic Forest. AB - The remarkable diversity of Eupatorieae in the Brazilian flora has received little study, despite the tribe's very high levels of endemism and importance in the threatened Cerrado and the Atlantic Forest biodiversity hotspots. Eupatorieae are one of the largest tribes in Asteraceae with 14 of 19 recognized subtribes occurring in Brazil. We constructed the largest phylogeny of Brazilian Eupatorieae to date that sampled the nrITS and ETS, chloroplast ndhI and ndhF genes, and the ndhI-ndhG intergenic spacer for 183 species representing 77 of the 85 Brazilian genera of the tribe. Maximum likelihood and Bayesian phylogenetic analyses showed that these species are not collectively monophyletic, so their distribution reflects multiple introductions into Brazil. A novel clade was found that includes 75% of the genera endemic to Brazil (Cerrado-Atlantic Forest Eupatorieae, "CAFE" clade). This radiation of at least 247 species concentrated in the Cerrado and Atlantic Forest biomes of central eastern Brazil is <7 my old and exhibits several ecologically diverse life forms. Eight subtribes of Brazilian Eupatorieae (Ageratinae, Alomiinae, Ayapaninae, Critoniinae, Disynaphiinae, Eupatoriinae, Gyptidinae and Hebecliniinae) and 16 genera (Ageratum, Agrianthus, Austroeupatorium, Bejaranoa, Chromolaena, Critonia, Disynaphia, Grazielia, Hatschbachiella, Heterocondylus, Koanophyllon, Lasiolaena, Neocabreria, Praxelis, Stylotrichium, and Symphyopappus) were found to be polyphyletic. We attribute incongruities between the molecular phylogenetic results and the current classification of the tribe mostly to convergent evolution of morphological characters traditionally used in the classification of the tribe. We used these phylogenetic results to suggest changes to the classification of some subtribes and genera of Eupatorieae that occur in Brazil. PMID- 26667032 TI - Erratum. PMID- 26667033 TI - Post-concussive complaints after mild traumatic brain injury associated with altered brain networks during working memory performance. AB - The aim was to investigate brain network function during working memory (WM) task performance in patients with uncomplicated mild traumatic brain injury (mTBI) in the sub-acute phase post-injury. We were particularly interested in differences between patients with (PCC-present) and without post-concussive complaints (PCC absent). Fifty-two patients and twenty healthy controls (HCs) (matched for age, sex, education and handedness) were included. Two patient groups were created based on reported post-concussive complaints at two weeks post-injury: PCC present (n = 32) and PCC-absent (n = 20). Functional MRI scans were made at approximately four weeks post-injury. Participants performed an n-back task consisting of three conditions (0-, 1- and 2-back) with increasing difficulty. General linear model analysis was performed to investigate activation patterns. Independent component analysis was used to identify brain networks. The frontal executive network (FEN), frontoparietal network (FPN) and default mode network (DMN) were selected for further analyses based on their highest task-relatedness. Task accuracy and reaction times were similar for patients with mTBI and HCs. During high WM load (2-vs.0-back contrast), mTBI patients exhibited lower activation within the medial prefrontal cortex compared to HCs. No differences were found between PCC-present and PCC-absent patients. Regarding network function, PCC-absent patients showed stronger deactivation of the DMN compared to PCC-present patients and HCs, especially during difficult task conditions. Furthermore, functional connectivity between the DMN and FEN was lower in PCC absent patients compared to PCC-present patients. Interestingly, network function did not differ between PCC-present patients and HCs, suggesting that non-injury related factors may underlie post-concussive complaints after mTBI. PMID- 26667034 TI - Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes. AB - The dopamine beta-hydroxylase (DbetaH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 MUg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes. PMID- 26667035 TI - Multiple Functions of the Eya Phosphotyrosine Phosphatase. AB - Eyes absent (Eya), a protein conserved from plants to humans and best characterized as a transcriptional coactivator, is also the prototype for a novel class of eukaryotic aspartyl protein tyrosine phosphatases. This minireview discusses recent breakthroughs in elucidating the substrates and cellular events regulated by Eya's tyrosine phosphatase function and highlights some of the complexities, new questions, and surprises that have emerged from efforts to understand how Eya's unusual multifunctionality influences developmental regulation and signaling. PMID- 26667036 TI - C/EBPgamma Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4. AB - The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPgamma:ATF4 heterodimers, but not C/EBPbeta:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPgamma and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPbeta and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg(-/-) mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPgamma-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg(-/-) mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPgamma as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID- 26667037 TI - Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product. AB - In the yeast Saccharomyces cerevisiae, the switch from respiratory metabolism to fermentation causes rapid decay of transcripts encoding proteins uniquely required for aerobic metabolism. Snf1, the yeast ortholog of AMP-activated protein kinase, has been implicated in this process because inhibiting Snf1 mimics the addition of glucose. In this study, we show that the SNF1-dependent ADH2 promoter, or just the major transcription factor binding site, is sufficient to confer glucose-induced mRNA decay upon heterologous transcripts. SNF1 independent expression from the ADH2 promoter prevented glucose-induced mRNA decay without altering the start site of transcription. SNF1-dependent transcripts are enriched for the binding motif of the RNA binding protein Vts1, an important mediator of mRNA decay and mRNA repression whose expression is correlated with decreased abundance of SNF1-dependent transcripts during the yeast metabolic cycle. However, deletion of VTS1 did not slow the rate of glucose induced mRNA decay. ADH2 mRNA rapidly dissociated from polysomes after glucose repletion, and sequences bound by RNA binding proteins were enriched in the transcripts from repressed cells. Inhibiting the protein kinase A pathway did not affect glucose-induced decay of ADH2 mRNA. Our results suggest that Snf1 may influence mRNA stability by altering the recruitment activity of the transcription factor Adr1. PMID- 26667038 TI - A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility. AB - Transmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16A and -16B serve as Ca(2+)-dependent Cl(-) channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca(2+)-dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35 amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca(2+)-dependent scrambling. We next established TMEM16E deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E(-/-) sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility. PMID- 26667039 TI - SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3beta. AB - Tissue fibrosis is a major cause of organ dysfunction during chronic diseases and aging. A critical step in this process is transforming growth factor beta1 (TGF beta1)-mediated transformation of fibroblasts into myofibroblasts, cells capable of synthesizing extracellular matrix. Here, we show that SIRT3 controls transformation of fibroblasts into myofibroblasts via suppressing the profibrotic TGF-beta1 signaling. We found that Sirt3 knockout (KO) mice with age develop tissue fibrosis of multiple organs, including heart, liver, kidney, and lungs but not whole-body SIRT3-overexpressing mice. SIRT3 deficiency caused induction of TGF-beta1 expression and hyperacetylation of glycogen synthase kinase 3beta (GSK3beta) at residue K15, which negatively regulated GSK3beta activity to phosphorylate the substrates Smad3 and beta-catenin. Reduced phosphorylation led to stabilization and activation of these transcription factors regulating expression of the profibrotic genes. SIRT3 deacetylated and activated GSK3beta and thereby blocked TGF-beta1 signaling and tissue fibrosis. These data reveal a new role of SIRT3 to negatively regulate aging-associated tissue fibrosis and discloses a novel phosphorylation-independent mechanism controlling the catalytic activity of GSK3beta. PMID- 26667041 TI - Sirtuins-mediators of maternal obesity-induced complications in offspring? AB - Obesity is a complex metabolic disease, attributed to diverse and interactive genetic and environmental factors. The associated health consequences of obesity are pleiotropic, with individuals being more susceptible to chronic diseases such as type 2 diabetes mellitus, hypertension, and lipotoxicity-related chronic diseases. The contribution of maternal obesity to the offspring's predisposition to both obesity and its complications is increasingly recognized. Understanding the mechanisms underlying these "transmissible" effects is critical to develop therapeutic interventions to reduce the risk for "programmed" obesity. Sirtuins (SIRTs), particularly SIRT1 and SIRT3, are NAD(+)-dependent deacetylases that regulate metabolic balance and stress responses in both central and peripheral tissues, of which dysregulation is a well-established mediator for the development and effects of obesity. Nevertheless, their implication in the transmissible effects of maternal obesity across generations remains largely elusive. In this review, we examine multiple pathways and systems that are likely to mediate such effects, with particular emphasis on the role of SIRTs.-Nguyen, L. T., Chen, H., Pollock, C. A., Saad, S. Sirtuins-mediators of maternal obesity induced complications in offspring? PMID- 26667040 TI - WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. AB - Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation ofWnt5a(but notWnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH responsive genesin vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signalingviathe WNT/Ca(2+)or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both beta-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decreaseviaa glycogen synthase kinase-3beta-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.-Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. PMID- 26667043 TI - Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis. AB - Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of the experimental conditions and testing techniques are provided.-Szarek, D., Marycz, K., Lis, A., Zawada, Z., Tabakow, P., Laska, J., Jarmundowicz, W. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis. PMID- 26667042 TI - Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation. AB - Embryo implantation requires that the uterus differentiate into the receptive state. Failure to attain uterine receptivity will impede blastocyst attachment and result in a compromised pregnancy. The molecular mechanism by which the uterus transitions from the prereceptive to the receptive stage is complex, involving an intricate interplay of various molecules. We recently found that mice with uterine deletion ofMsxgenes (Msx1(d/d)/Msx2(d/d)) are infertile because of implantation failure associated with heightened apicobasal polarity of luminal epithelial cells during the receptive period. However, information on Msx's roles in regulating epithelial polarity remains limited. To gain further insight, we analyzed cell-type-specific gene expression by RNA sequencing of separated luminal epithelial and stromal cells by laser capture microdissection fromMsx1(d/d)/Msx2(d/d)and floxed mouse uteri on d 4 of pseudopregnancy. We found that claudin-1, a tight junction protein, and small proline-rich (Sprr2) protein, a major component of cornified envelopes in keratinized epidermis, were substantially up-regulated inMsx1(d/d)/Msx2(d/d)uterine epithelia. These factors also exhibited unique epithelial expression patterns at the implantation chamber (crypt) inMsx1(f/f)/Msx2(f/f)females; the patterns were lost inMsx1(d/d)/Msx2(d/d)epithelia on d 5, suggesting important roles during implantation. The results suggest thatMsxgenes play important roles during uterine receptivity including modulation of epithelial junctional activity.-Sun, X., Park, C. B., Deng, W., Potter, S. S., Dey, S. K. Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation. PMID- 26667044 TI - Cell Wall-Anchored Surface Proteins of Staphylococcus aureus: Many Proteins, Multiple Functions. AB - Staphylococcus aureus persistently colonizes about 20 % of the population and is intermittently associated with the remainder. The organism can cause superficial skin infections and life-threatening invasive diseases. The surface of the bacterial cell displays a variety of proteins that are covalently anchored to peptidoglycan. They perform many functions including adhesion to host cells and tissues, invasion of non-phagocytic cells, and evasion of innate immune responses. The proteins have been categorized into distinct classes based on structural and functional analysis. Many surface proteins are multifunctional. Cell wall-anchored proteins perform essential functions supporting survival and proliferation during the commensal state and during invasive infections. The ability of cell wall-anchored proteins to bind to desquamated epithelial cells is important during colonization, and the binding to fibrinogen is of particular significance in pathogenesis. PMID- 26667045 TI - The Innate Immune Response Against Staphylococcus aureus. AB - The innate immune system harbors a multitude of different receptor systems and cells that are constantly prepared to sense and eliminate invading microbial pathogens. Staphylococcus aureus enters the body on its exposed epithelial surfaces, e.g., on skin and mucosa. The initial interaction with epithelial cells is governed by Toll-like receptor (TLR)-2-mediated local production of soluble mediators, including cytokines, chemokines, and antimicrobial peptides. The overall goal is to achieve a steady state of immune mediators and colonizing bacteria. Following cell and tissue invasion clearance of bacteria depends on intracellular microbial sensors and subsequent activation of the inflammasomes. Tissue-resident mast cells and macrophages recruit neutrophils, macrophages, and NK cells. This inflammatory response supports the generation of IL-17 producing NKT, gammadelta T cells, and T helper cells. Local dendritic cells migrate to the lymph nodes and fine-tune the adaptive immune response. The scope of this chapter is to provide an overview on the major cell types and receptors involved in innate immune defense against S. aureus. By segregating the different stages of infection from epithelial barrier to intracellular and systemic infection, this chapter highlights the different qualities of the innate immune response to S. aureus at different stages of invasiveness. PMID- 26667046 TI - Connecting Refugees to Substance Use Treatment: A Qualitative Study. AB - An emerging body of literature identifies substance use as a growing concern among refugees resettling in the United States. Like immigrants, refugees may face cultural, linguistic, or systems barriers to connecting with mainstream substance use treatment programs, which may be compounded by refugees' unique experiences with exposure to trauma, displacement in refugee camps, and resettlement. This qualitative study explores factors that support and prevent refugees from connecting with chemical health treatment. Fifteen participants who identified as social service or public health professionals who work with refugees responded to an online, semistructured survey about their experiences referring refugees to substance use treatment. Resulting data was analyzed using thematic analysis. Themes emerged identifying a lack of culturally informed treatment models, policy issues, and client characteristics such as motivation and past trauma as barriers to engaging with treatment. Ongoing case management and coordination were identified as important to successful linkage. Findings from this study contribute to a better understanding of how to support refugees seeking substance use treatment and suggest that developing trauma informed, culturally relevant models of treatment that are integrated with primary health care and geographically accessible may enhance treatment linkage. PMID- 26667047 TI - Atypical cartilaginous tumor/chondrosarcoma, grade 1, of the mastoid in three family members: A new entity. AB - We present a case series of a family with three members having cartilaginous tumors of the mastoid. All patients presented between the ages of 9 to 12 years with acute onset facial nerve paralysis. Histologic analysis of all tumors showed similar features, consistent with atypical cartilaginous tumors/chondrosarcoma, low-grade. Conventional cytogenetic analysis performed on one of the sons' tumor showed no evidence of chromosomal abnormality. High-resolution array comparative genomic hybridization performed on the same patient's blood also showed no unbalanced chromosomal abnormality. This is the first report of family members with this unusual combination of clinical, radiologic, and histologic finding. Laryngoscope, 126:E310-E313, 2016. PMID- 26667049 TI - Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma-COPD overlap syndrome and bronchial asthma. AB - BACKGROUND: Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma-COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls. METHODS: Ascorbic acid (AA), carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, alpha-carotene, beta carotene and lycopene), retinol and alpha-tocopherol levels in plasma were determined by using a high performance liquid chromatography. Reduced glutathione (GSH), oxidised glutathione (GSSG) in whole blood and urinary 8-OHdG were also determined. RESULTS: Plasma AA level of COPD subjects was significantly lower than that of healthy elderly people. Conversely, ACOS and BA subjects showed no significant difference from healthy elderly people. Moreover, plasma lycopene and total carotenoid levels and GSH content in blood were significantly lower in COPD subjects than these in healthy elderly people. However, other redox markers such as GSSG, GSH/GSSG ratio and urinary 8-OHdG found no significant differences between COPD, ACOS and BA compared to healthy elderly people. CONCLUSIONS: These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA. PMID- 26667050 TI - 6-Amidopyrene as a label-assisted laser desorption/ionization (LA-LDI) enhancing tag: development of photoaffinity pyrene derivative. AB - Pyrene-conjugated compounds are detected by label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS) without matrixes. We found that 6-amidopyrene derivatives were highly detectable by the LDI MS instrument equipped with a 355 nm laser. In a certain case of a 6-amidopyrene derivative, a molecular ion peak [M](+*) and a characteristic fragment ion peak [M-42](+*) were detected in an amount of only 10 fmol. The latter peak, corresponding to the 6 aminopyrene fragment, might be generated in situ by the removal of ketene (CH2=C=O) from the parent molecule. A photoaffinity amidopyrene derivative of an antitumor macrolide aplyronine A (ApA-PaP) was synthesized, which showed potent cytotoxicity and actin-depolymerizing activity. In an LDI MS analysis of the MeOH and water-adducts of ApA-PaP, oxime N-O bonds as well as amidopyrene N-acetyl moieties were preferentially cleaved, and their internal structures were confirmed by MS/MS analysis. Amidopyrene moiety might enhance fragmentation and stabilize the cleaved fragments by intramolecular or intermolecular weak interactions including hydrogen bonding. Our chemical probe methods might contribute to a detailed analysis of binding modes between various ligands and target biomacromolecules that include multiple and weak interactions. PMID- 26667051 TI - Mode of drinking fluoridated milk: effect on intraoral fluoride concentrations. AB - OBJECTIVE: To determine the effect of the mode of drinking fluoridated milk on salivary and plaque fluoride concentrations. METHODS: Fluoridated milk was ingested by 32 children in three ways: (a) directly from the container (1.0 and 5.0 mg F/litre), (b) through a straw with the tip between the lips (5.0 mg F/litre), and (c) with the tip deep in the oral cavity (5.0 mg F/litre). Saliva was collected at baseline and 2, 15, and 40 min and plaque at baseline and 20 min after drinking. Fluoride concentrations were determined using the electrode after HMDS-facilitated diffusion. RESULTS: The mode of drinking did not affect fluoride concentrations in saliva or plaque. The average 2-min salivary concentrations were 65 ng F/mL for the 1.0 mg F/litre group and 276 ng F/mL for the three 5.0 mg F/litre groups (P < 0.01). The average of the 15- and 40-min salivary concentrations was 22 ng F/mL for the 1.0 mg F/litre group and 41 ng F/mL for the 5.0 mg F/litre groups (P < 0.01). Plaque concentrations showed the same patterns as in saliva, that is, they were higher in the three 5.0 mg F/litre groups than in the 1.0 mg F/litre group and the differences among the 5.0 mg F/litre groups were not statistically significant. CONCLUSION: Salivary and plaque fluoride concentrations were independent of the mode of drinking but directly related to milk fluoride concentrations. PMID- 26667048 TI - Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts. AB - DNA hypomethylation in certain genes is associated with tobacco exposure but it is unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of DNA from pre-diagnostic blood samples from 132 case-control pairs in the NOWAC cohort, we observe that the most significant associations with lung cancer risk are for cg05575921 in AHRR (OR for 1 s.d.=0.37, 95% CI: 0.31-0.54, P-value=3.3 * 10(-11)) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31-0.56, P-value=3.9 * 10(-10)), previously shown to be strongly hypomethylated in smokers. These associations remain significant after adjustment for smoking and are confirmed in additional 664 case-control pairs tightly matched for smoking from the MCCS, NSHDS and EPIC HD cohorts. The replication and mediation analyses suggest that residual confounding is unlikely to explain the observed associations and that hypomethylation of these CpG sites may mediate the effect of tobacco on lung cancer risk. PMID- 26667052 TI - The prevalence of unique SNPs in the renin-angiotensin system highlights the need for pharmacogenetics in Indigenous Australians. AB - Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms (SNPs) in genes of the renin-angiotensin system (RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations (P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines. PMID- 26667054 TI - Sustainable energy supply and consumption by 2050 and outlook towards the end of the century: Possible scientific breakthroughs. PMID- 26667055 TI - Closing the carbon cycle through rational use of carbon-based fuels. AB - In this paper, a brief overview is presented of natural gas as a fuel resource with subsequent carbon capture and re-use as a means to facilitate reduction and eventual elimination of man-made carbon emissions. A particular focus is shale gas and, to a lesser extent, methane hydrates, with the former believed to provide the most reasonable alternative as a transitional fuel toward a low carbon future. An emphasis is placed on the gradual elimination of fossil resource usage as a fuel over the coming 35 to 85 years and its eventual replacement with renewable resources and nuclear power. Furthermore, it is proposed that synthesis of chemical feedstocks from recycled carbon dioxide and hydrogen-rich materials should be undertaken for specific applications in the transport sector which require access to high energy density fuels. To achieve the latter, carbon dioxide capture is imperative and possible synthetic routes for chemical feedstock production are briefly reviewed. PMID- 26667053 TI - Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy. AB - BACKGROUND: Plasmodium falciparum malaria is a significant public health problem in Comoros, and artemisinin combination therapy (ACT) remains the first choice for treating acute uncomplicated P. falciparum. The emergence and spread of artemisinin-resistant P. falciparum in Southeast Asia, associated with mutations in K13-propeller gene, poses a potential threat to ACT efficacy. Detection of mutations in the P. falciparum K13-propeller gene may provide the first-hand information on changes in parasite susceptibility to artemisinin. The objective of this study is to determinate the prevalence of mutant K13-propeller gene among the P. falciparum isolates collected from Grande Comore Island, Union of Comoros, where ACT has been in use since 2004. METHODS: A total of 207 P. falciparum clinical isolates were collected from the island during March 2006 and October 2007 (n = 118) and March 2013 and December 2014 (n = 89). All isolates were analysed for single nucleotide polymorphisms (SNPs) and haplotypes in the K13 propeller gene using nested PCR and DNA sequencing. RESULTS: Only three 2006-2007 samples carried SNPs in the K13-propeller gene, one having a synonymous (G538G) and the other having two non-synonymous (S477Y and D584E) substitutions leading to two mutated haplotypes (2.2%, 2/95). Three synonymous mutations (R471R, Y500Y, and G538G) (5.9%, 5/85) and 7 non-synonymous substitutions (21.2%, 18/85) with nine mutated haplotypes (18.8%, 16/85) were found in isolates from 2013 to 2014. However, none of the polymorphisms associated with artemisinin-resistance in Southeast Asia was detected from any of the parasites examined. CONCLUSION: This study showed increased K13-propeller gene diversity among P. falciparum populations on the Island over the course of 8 years (2006-2014). Nevertheless, none of the polymorphisms known to be associated with artemisinin resistance in Asia was detected in the parasite populations examined. Our data suggest that P. falciparum populations in Grande Comore are still effectively susceptible to artemisinin. Our results provide insights into P. falciparum populations regarding mutations in the gene associated with artemisinin resistance and will be useful for developing and updating anti-malarial guidance in Comoros. PMID- 26667056 TI - Solar energy for electricity and fuels. AB - Solar energy conversion into electricity by photovoltaic modules is now a mature technology. We discuss the need for materials and device developments using conventional silicon and other materials, pointing to the need to use scalable materials and to reduce the energy payback time. Storage of solar energy can be achieved using the energy of light to produce a fuel. We discuss how this can be achieved in a direct process mimicking the photosynthetic processes, using synthetic organic, inorganic, or hybrid materials for light collection and catalysis. We also briefly discuss challenges and needs for large-scale implementation of direct solar fuel technologies. PMID- 26667057 TI - From first generation biofuels to advanced solar biofuels. AB - Roadmaps towards sustainable bioeconomy, including the production of biofuels, in many EU countries mostly rely on biomass use. However, although biomass is renewable, the efficiency of biomass production is too low to be able to fully replace the fossil fuels. The use of land for fuel production also introduces ethical problems in increasing the food price. Harvesting solar energy by the photosynthetic machinery of plants and autotrophic microorganisms is the basis for all biomass production. This paper describes current challenges and possibilities to sustainably increase the biomass production and highlights future technologies to further enhance biofuel production directly from sunlight. The biggest scientific breakthroughs are expected to rely on a new technology called "synthetic biology", which makes engineering of biological systems possible. It will enable direct conversion of solar energy to a fuel from inexhaustible raw materials: sun light, water and CO2. In the future, such solar biofuels are expected to be produced in engineered photosynthetic microorganisms or in completely synthetic living factories. PMID- 26667058 TI - Fuel cells are a commercially viable alternative for the production of "clean" energy. AB - Fuel cells present a highly efficient and environmentally friendly alternative technology for decentralized energy production. The scope of the present study is to provide an overview of the technological and commercialization readiness level of fuel cells. Specifically, there is a brief description of their general advantages and weaknesses in correlation with various technological actions and political strategies, which are adopted towards their proper positioning in the global market. Some of the most important key performance indicators are also discussed, alongside with a few examples of broad commercialization. It is concluded that the increasing number of companies which utilize and invest on this technology, in combination with the supply chain improvements and the concomitant technological maturity and recognition, reinforce the fuel cell industry so as to become well-aligned for global success. PMID- 26667059 TI - Nuclear power in the 21st century: Challenges and possibilities. AB - The current situation and possible future developments for nuclear power- including fission and fusion processes--is presented. The fission nuclear power continues to be an essential part of the low-carbon electricity generation in the world for decades to come. There are breakthrough possibilities in the development of new generation nuclear reactors where the life-time of the nuclear waste can be reduced to some hundreds of years instead of the present time-scales of hundred thousand of years. Research on the fourth generation reactors is needed for the realisation of this development. For the fast nuclear reactors, a substantial research and development effort is required in many fields--from material sciences to safety demonstration--to attain the envisaged goals. Fusion provides a long-term vision for an efficient energy production. The fusion option for a nuclear reactor for efficient production of electricity has been set out in a focussed European programme including the international project of ITER after which a fusion electricity DEMO reactor is envisaged. PMID- 26667060 TI - Challenges and opportunities of power systems from smart homes to super-grids. AB - The world's power systems are facing a structural change including liberalization of markets and integration of renewable energy sources. This paper describes the challenges that lie ahead in this process and points out avenues for overcoming different problems at different scopes, ranging from individual homes to international super-grids. We apply energy system models at those different scopes and find a trade-off between technical and social complexity. Small-scale systems would require technological breakthroughs, especially for storage, but individual agents can and do already start to build and operate such systems. In contrast, large-scale systems could potentially be more efficient from a techno economic point of view. However, new political frameworks are required that enable long-term cooperation among sovereign entities through mutual trust. Which scope first achieves its breakthrough is not clear yet. PMID- 26667061 TI - Energy efficiency of engines and appliances for transport on land, water, and in air. AB - The transport sector is fundamental for the economy but also for personal life. With a growing population and the globalization process, it is not surprising that the demand of transport is set to grow in the near future and certainly until 2050. This paper focuses on the huge potential of progress in the sector of technology for transport. As the principal sector for transport will remain on roads, the paper emphasizes the progress in the automotive sector. Since car manufacturers are investing massively into research and technology development to offer ever more efficient cars--not only energy efficient but also efficient in terms of safety and comfort--the car of tomorrow will be very different from the present one. The increasing role of electronics in cars will synergistically cooperate with that of so-called smart cities. The potential development of methane in the transport sector, mainly used for heavy transportation is discussed. PMID- 26667062 TI - Selective hydrogenation of nitriles to primary amines catalyzed by a novel iron complex. AB - Hydrogenation of nitriles to primary amines constitutes an atom-efficient and environmentally benign synthetic reaction. Herein we present a novel complex based on earth-abundant iron, and its application in the catalytic homogeneous hydrogenation of (hetero)aromatic, benzylic, and aliphatic nitriles to selectively form primary amines. PMID- 26667063 TI - Thermal curing of a self-assembled monolayer at the nanoscale. AB - On fabrication by contact printing, a nanostructured self-assembled monolayer (SAM) of alkanethiol contains a substantial fraction of unbound molecules that are either inverted among other upright molecules or piled on top of the SAM. The molecular dynamics simulation in the present study demonstrates that thermal annealing cures these defects for a SAM island of octadecanethiol. The SAM island melted partially as a result of heating, so the unbound molecules that had piled on top of the SAM island penetrated down to make contact with the surface, and the inverted molecules flipped to achieve adsorption. With subsequent cooling, the packing of sulfur atoms and alignment of alkyl chains of the SAM island were recovered. The molecular pathways for the adsorption of the unbound molecules were unraveled. The transition state and activation energy, calculated for each pathway in the absence of annealing, showed that these defects are incurable without the help of annealing. PMID- 26667064 TI - Single particle optical extinction and scattering allows real time quantitative characterization of drug payload and degradation of polymeric nanoparticles. AB - The behavior of nanoparticles in biological systems is determined by their dimensions, size distribution, shape, surface chemistry, density, drug loading and stability; the characterization of these parameters in realistic conditions and the possibility to follow their evolution in vitro and in vivo are, in most of the cases, far from the capabilities of the standard characterization technologies. Optical techniques such as dynamic light scattering (DLS) are, in principle, well suited for in line characterization of nanoparticle, however their fail in characterizing the evolution of nanoparticle in solution where change in particle dimension and density is present. Here we present an in-line optical technique based on single particle extinction and scattering (SPES) overcoming the limitations typical of DLS and allowing for the efficient characterization of nanoparticle polydispersity, index of refraction and degradation dynamics in solution. Using SPES, we characterized the evolution of PLGA nanoparticles with different structures and drug payloads in solution and we compared the results with DLS. Our results suggest that SPES could be used as a process analytical technology for pharmaceutical nanoparticle production. PMID- 26667065 TI - From neutrophils to macrophages: differences in regional adipose tissue depots. AB - Currently, we do not fully understand the underlying mechanisms of how regional adiposity promotes metabolic dysregulation. As adipose tissue expands, there is an increase in chronic systemic low-grade inflammation due to greater infiltration of immune cells and production of cytokines. This chronic inflammation is thought to play a major role in the development of metabolic complications and disease such as insulin resistance and diabetes. We know that different adipose tissue depots contribute differently to the risk of metabolic disease. People who have an upper body fat distribution around the abdomen are at greater risk of disease than those who tend to store fat in their lower body around the hips and thighs. Thus, it is conceivable that adipose tissue depots contribute differently to the inflammatory milieu as a result of varied infiltration of immune cell types. In this review, we describe the role and function of major resident immune cells in the development of adipose tissue inflammation and discuss their regional differences in the context of metabolic disease risk. We find that although initial studies have found regional differences, a more comprehensive understanding of how immune cells interrupt adipose tissue homeostasis is needed. PMID- 26667066 TI - Discrimination of two-qubit unitaries via local operations and classical communication. AB - Distinguishability is a fundamental and operational measure generally connected to information applications. In quantum information theory, from the postulates of quantum mechanics it often has an intrinsic limitation, which then dictates and also characterises capabilities of related information tasks. In this work, we consider discrimination between bipartite two-qubit unitary transformations by local operations and classical communication (LOCC) and its relations to entangling capabilities of given unitaries. We show that a pair of entangling unitaries which do not contain local parts, if they are perfectly distinguishable by global operations, can also be perfectly distinguishable by LOCC. There also exist non-entangling unitaries, e.g. local unitaries, that are perfectly discriminated by global operations but not by LOCC. The results show that capabilities of LOCC are strictly restricted than global operations in distinguishing bipartite unitaries for a finite number of repetitions, contrast to discrimination of a pair of bipartite states and also to asymptotic discrimination of unitaries. PMID- 26667067 TI - Smoking and gingivitis: focus on inducible nitric oxide synthase, nitric oxide and basic fibroblast growth factor. AB - BACKGROUND: Periodontal disease pathogenesis has been associated with smoking. Gingivitis is a mild and reversible form of periodontal disease and it tends to progress to periodontitis only in susceptible individuals. In the present study, we aimed to examine the impact of smoking on host responses in gingivitis and to evaluate and compare the inducible nitric oxide synthase (iNOS) activity in gingival tissue and NO and basic fibroblast growth factor (bFGF) levels in the gingival crevicular fluid of patients with gingivitis and healthy individuals. MATERIAL AND METHODS: Forty-one participants were assigned to the gingivitis smoker (n = 13), gingivitis (n = 13), healthy-smoker (n = 7) and healthy groups (n = 8). Clinical indices were recorded; gingival biopsy and gingival crevicular fluid samples were obtained from papillary regions. iNOS expression was evaluated by immunohistochemical staining. The immunoreactive cells were semiquantitatively assessed. For the quantitative determination of nitrite and nitrate in gingival crevicular fluid, the NO assay kit was used. The amount of bFGF in gingival crevicular fluid was determined by enzyme-linked immunosorbent assay. RESULTS: The gingivitis-smoker group demonstrated a stronger iNOS expression than the non smoker gingivitis group. iNOS expression intensity was lower in the non-smoker healthy group compared to that in healthy-smokers. No significant gingival crevicular fluid NO and bFGF level changes were observed between groups. Among patients with gingivitis, a positive correlation was detected between gingival crevicular fluid NO and bFGF levels (r = 0.806, p = 0.001). CONCLUSIONS: Our data suggest that smoking has significant effects on iNOS expression but not on gingival crevicular fluid NO or bFGF levels in healthy and patients with gingivitis. However, our results suggest that bFGF might be involved in the regulation of NO production via iNOS. PMID- 26667068 TI - Asymmetric Organocatalytic Reductive Coupling Reactions between Benzylidene Pyruvates and Aldehydes. AB - An organocatalytic three-component reductive coupling reaction between dimethyl phosphite, benzylidene pyruvates, and aldehydes is reported. A chiral triaryliminophosphorane catalyst promotes Pudovik addition, which is followed by phospha-Brook rearrangement to transiently generate enolates that are trapped stereoselectively by aldehydes. This reductive coupling provides vicinal polyfunctionalized stereocenters from readily available prochiral starting materials with excellent diastereoselectivity, enantioselectivity, and yield. PMID- 26667069 TI - Safety of mTOR inhibitors in adult solid organ transplantation. AB - INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). By inhibiting the ubiquitous mTOR pathway, they present a peculiar safety profile. The increased incidence of serious adverse events in early studies halted the enthusiasm as a kidney sparing alternative to calcineurin inhibitors (CNI). AREAS COVERED: Herein we review mTOR inhibitors safety profile for adult organ transplantation, ranging from acute side effects, such as lymphoceles, delayed wound healing, or cytopenias, to long-term ones which increase morbidity and mortality, such as cancer risk and metabolic profile. Infection, proteinuria, and cutaneous safety profiles are also addressed. EXPERT OPINION: In the authors' opinion, mTOR inhibitors are a safe alternative to standard immunosuppression therapy with CNI and mycophenolate/azathioprine. Mild adverse events can be easily managed with an increased awareness and close monitoring of trough levels. Most serious side effects are dose- and organ-dependent. In kidney and heart transplantation mTOR inhibitors may be safely used as either low-dose de novo or through early conversion. In the liver, conversion 4 weeks post-transplantation may reduce long term chronic kidney disease secondary to calcineurin nephrotoxicity, without increasing hepatic artery/portal vein thrombosis. PMID- 26667070 TI - Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment. PMID- 26667072 TI - Cortico-Basal Ganglia Circuit Function in Psychiatric Disease. AB - Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders. PMID- 26667073 TI - Ceramide Signaling and Metabolism in Pathophysiological States of the Lung. AB - Following the discovery of ceramide as the central signaling and metabolic relay among sphingolipids, studies of its involvement in lung health and pathophysiology have exponentially increased. In this review, we highlight key studies in the context of recent progress in metabolomics and translational research methodologies. Evidence points toward an important role for the ceramide/sphingosine-1-phosphate rheostat in maintaining lung cell survival, vascular barrier function, and proper host response to airway microbial infections. Sphingosine kinase 1 has emerged as an important determinant of sphingosine-1-phosphate lung levels, which, when aberrantly high, contribute to lung fibrosis, maladaptive vascular remodeling, and allergic asthma. New sphingolipid metabolites have been discovered as potential biomarkers of several lung diseases. Although multiple acute and chronic lung pathological conditions involve perturbations in sphingolipid signaling and metabolism, there are specific patterns, unique sphingolipid species, enzymes, metabolites, and receptors, which have emerged that deepen our understanding of lung pathophysiology and inform the development of new therapies for lung diseases. PMID- 26667071 TI - Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology. AB - Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Here we summarize what is known about exosome biogenesis, content, and transmission, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the questions currently under active investigation regarding these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications. PMID- 26667074 TI - Glucocorticoid Signaling: An Update from a Genomic Perspective. AB - Glucocorticoid hormones (GC) regulate essential physiological functions including energy homeostasis, embryonic and postembryonic development, and the stress response. From the biomedical perspective, GC have garnered a tremendous amount of attention as highly potent anti-inflammatory and immunosuppressive medications indispensable in the clinic. GC signal through the GC receptor (GR), a ligand dependent transcription factor whose structure, DNA binding, and the molecular partners that it employs to regulate transcription have been under intense investigation for decades. In particular, next-generation sequencing-based approaches have revolutionized the field by introducing a unified platform for a simultaneous genome-wide analysis of cellular activities at the level of RNA production, binding of transcription factors to DNA and RNA, and chromatin landscape and topology. Here we describe fundamental concepts of GC/GR function as established through traditional molecular and in vivo approaches and focus on the novel insights of GC biology that have emerged over the last 10 years from the rapidly expanding arsenal of system-wide genomic methodologies. PMID- 26667075 TI - Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function. AB - Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. In this review, we delineate the architecture of mitochondria and define the mechanisms by which they modify their shape. Key players in these mechanisms are discussed, along with their role in manipulating mitochondrial morphology during cellular action and development. Throughout, we highlight the evolutionary context in which mitochondrial dynamics emerged and consider unanswered questions whose dissection might lead to mitochondrial morphology based therapies. PMID- 26667076 TI - Role of Intestinal HIF-2alpha in Health and Disease. AB - The intestine is supported by a complex vascular system that undergoes dynamic and transient daily shifts in blood perfusion, depending on the metabolic state. Moreover, the intestinal villi have a steep oxygen gradient from the hypoxic epithelium adjacent to the anoxic lumen to the relative higher tissue oxygenation at the base of villi. Due to the daily changes in tissue oxygen levels in the intestine, the hypoxic transcription factors hypoxia-inducible factor (HIF) 1alpha and HIF-2alpha are essential in maintaining intestinal homeostasis. HIF 2alpha is essential in maintaining proper micronutrient balance, the inflammatory response, and the regenerative and proliferative capacity of the intestine following an acute injury. However, chronic activation of HIF-2alpha leads to enhanced proinflammatory response, intestinal injury, and colorectal cancer. In this review, we detail the major mechanisms by which HIF-2alpha contributes to health and disease of the intestine and the therapeutic implications of targeting HIF-2alpha in intestinal diseases. PMID- 26667079 TI - Structural Description of the Interface of Pickering Emulsions Stabilized by Cellulose Nanocrystals. AB - The cotton cellulose nanocrystals (CNCs) used in this study are rod-like particles with dimensions in the nanoscale (195 nm long, 23 nm width and 6 nm thick) able to stabilize Pickering emulsions. The adsorption of CNCs at an oil water interface has been investigated by small angle neutron scattering (SANS) with and without surface charge, and varying CNC concentration from 2 to 5 g/L. Average thicknesses of the interfacial CNC layer around the emulsion droplets of 7 and 18 nm were determined for charged and uncharged CNC, respectively, regardless of their concentration in suspension. This suggests that CNC particles lie as a monolayer varying in surface density. Using several phase contrast variations, the neutron wave vector (Q) dependence with the intensity showed that CNCs are in contact with the oil phase only via the surface of the CNC and not immersed in oil since the Porod behavior is observed over the whole Q-range revealing no deformation of the oil surface at a nanometer scale. This result promotes the postulate that the (2 0 0) crystalline plane of the CNC directly interacts with the interface. PMID- 26667077 TI - Regulation of Vascular and Renal Function by Metabolite Receptors. AB - To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and PMID- 26667080 TI - Genetic diversity of the Mycobacterium tuberculosis Beijing family based on multiple genotyping profiles. AB - Among the most prevalent Mycobacterium tuberculosis (Mtb) strains worldwide is the Beijing genotype, which has caused large outbreaks of tuberculosis (TB). Characteristics facilitating the dissemination of Beijing family strains remain unknown, but they are presumed to have been acquired through evolution of the lineage. To explore the genetic diversity of the Beijing family Mtb and explore the discriminatory ability of mycobacterial interspersed repetitive units variable number of tandem repeats (MIRU-VNTR) loci in several regions of East Asia, a cross-sectional study was conducted with a total of 163 Beijing strains collected from registered TB patients between 1 June 2009 and 31 November 2010 in Funing County, China. The isolated strains were analysed by 15-MIRU-VNTR loci typing and compared with published MIRU-VNTR profiles of Beijing strains. Synonymous single nucleotide polymorphisms at 10 chromosomal positions were also analysed. The combination of SNP and MIRU-VNTR typing may be used to assess Mtb genotypes in areas dominated by Beijing strains. The modern subfamily in Shanghai overlapped with strains from other countries, whereas the ancient subfamily was genetically differentiated across several countries. Modern subfamilies, especially ST10, were prevalent. Qub11b and four other loci (MIRU 26, Mtub21, Qub26, Mtub04) could be used to discriminate Beijing strains. PMID- 26667078 TI - ADAM Proteases and Gastrointestinal Function. AB - A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor alpha (TNFalpha) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis. PMID- 26667081 TI - Ruptured Pseudoaneurysm after Gamma Knife Surgery for Vestibular Schwannoma. AB - Ruptured aneurysms of anterior inferior cerebellar artery (AICA) after radiotherapy for vestibular schwannoma (VS) are rare, and no definite treatment has been established for distal AICA pseudoaneurysms. We describe a 61-year-old man who underwent Gamma Knife surgery (GKS) for left VS. Follow-up magnetic resonance imaging (MRI) revealed partial regression of the tumor. Twelve years after GKS, he suffered from subarachnoid hemorrhage. Initial angiogram showed no vascular lesions; second left vertebral angiogram, 10 days after admission, demonstrated a pseudoaneurysm in the lateral pontine segment of the left AICA. The proximal portion of the AICA was occluded by a coil. Postoperative MRI revealed an infarction on the left side of the pons and brachium pontis. Although the patient suffered from mild postoperative cerebellar ataxia and facial and abducens nerve palsy, he was discharged 1 month postoperatively requiring no assistance with activities of daily living. Twelve months later, he recovered satisfactorily with a modified Rankin Scale grade of 1, and no recanalization of the aneurysm was found on MR angiography. Endovascular parent artery occlusion for ruptured aneurysms at distal AICA carries the risk of brain stem infarction, but should be considered when no other option is available such as after radiotherapy for VS. PMID- 26667082 TI - Stent-assisted Coiling for Ruptured Basilar Artery Dissecting Aneurysms: An Initial Experience of Four Cases. AB - No treatment strategy has been established for subarachnoid hemorrhages due to basilar artery (BA) trunk dissecting aneurysms. Our aim was to report our initial experience performing stent-assisted coiling (SAC) for ruptured BA dissecting aneurysms to validate the effectiveness of this treatment. We experienced four consecutive cases of ruptured dissecting BA trunk aneurysm treated with SAC between 2008 and 2014 at three institutions. Aneurysm rebleeding was prevented without causing severe brainstem ischemia in all cases. In our opinion, both the blockage of the inflow to aneurysms and the preservation of the antegrade flow of the BA can be achieved by SAC, although controversies regarding long-term stability and appropriate antiplatelet therapy remain. PMID- 26667083 TI - Self-assembly of Carbon Vacancies in Sub-stoichiometric ZrC(1-x). AB - Sub-stoichiometric interstitial compounds, including binary transition metal carbides (MC(1-x)), maintain structural stability even if they accommodate abundant anion vacancies. This unique character endows them with variable composition, diverse-configuration and controllable-performance through composition and structure design. Herein, the evolution of carbon vacancy (VC) configuration in sub-stoichiometric ZrC(1-x) is investigated by combining the cluster expansion method and first-principles calculations. We report the interesting self-assembly of VCs and the fingerprint VC configuration (VC triplet constructed by 3(rd) nearest neighboring vacancies) in all the low energy structures of ZrC(1-x). When VC concentration is higher than the critical value of 0.5 (x > 0.5), the 2(nd) nearest neighboring VC configurations with strongly repulsive interaction inevitably appear, and meanwhile, the system energy (or formation enthalpy) of ZrC(1-x) increases sharply which suggests the material may lose phase stability. The present results clarify why ZrC(1-x) bears a huge amount of VCs, tends towards VC ordering, and retains stability up to a stoichiometry of x = 0.5. PMID- 26667084 TI - Reconstruction of ulnar defect with vascularized rib graft: A case report. AB - This case report describes the reconstruction of a segmental ulnar defect using a vascularized rib graft. A 27-year-old man was injured during military service by an improvised explosive device, resulting in bilateral through-the-knee amputations, left hand deformity, and a segmental left ulnar defect. After unsuccessful ulnar reconstruction with nonvascularized autologous bone and allograft bone substitutes, he presented to our institution. We removed the residual allograft fragments from the ulnar defect, harvested a vascularized left sixth rib with the intercostal artery and vein, secured the construct with internal hardware, and performed microanastomoses of the intercostal artery and vein to the posterior interosseous artery and vein. Postoperatively, he had a hematoma at the vascularized graft recipient site caused by anticoagulation therapy for his chronic deep vein thrombosis. Despite this, the rib graft successfully incorporated on the basis of radiographic and clinical examinations at 27 months. He had no pain and good function of the arm. The results of this case suggest that a vascularized rib graft for forearm reconstruction may be a viable option with minimal donor site morbidity. (c) 2015 Wiley Periodicals, Inc. Microsurgery 37:160-164, 2017. PMID- 26667085 TI - Neuropsychological Status and Structural Brain Imaging in Adolescents With Single Ventricle Who Underwent the Fontan Procedure. AB - BACKGROUND: Few studies have described the neuropsychological outcomes and frequency of structural brain or genetic abnormalities in adolescents with single ventricle who underwent the Fontan procedure. METHODS AND RESULTS: In a cross sectional, single-center study, we enrolled 156 subjects with single ventricle, mean age 14.5+/-2.9 years, who had undergone the Fontan procedure. Scores in the entire cohort on a standard battery of neuropsychological tests were compared with those of normative populations or to those of a group of 111 locally recruited healthy adolescents. They also underwent brain magnetic resonance imaging and were evaluated by a clinical geneticist. Genetic abnormalities were definite in 16 subjects (10%) and possible in 49 subjects (31%). Mean Full-Scale IQ was 91.6+/-16.8, mean Reading Composite score was 91.9+/-17.2, and mean Mathematics Composite score was 92.0+/-22.9, each significantly lower than the population means of 100+/-15. Mean scores on other neuropsychological tests were similarly lower than population norms. In multivariable models, risk factors for worse neuropsychological outcomes were longer total support and circulatory arrest duration at first operation, presence of a genetic abnormality, more operations and operative complications, more catheterization complications, and seizure history. The frequency of any abnormality on magnetic resonance imaging was 11 times higher among Fontan adolescents than referents (66% versus 6%); 19 (13%) patients had evidence of a stroke, previously undiagnosed in 7 patients (40%). CONCLUSIONS: The neuropsychological deficits and high frequencies of structural brain abnormalities in adolescents who underwent the Fontan procedure highlight the need for research on interventions to improve the long-term outcomes in this high-risk group. PMID- 26667086 TI - Simplified Predictive Instrument to Rule Out Acute Coronary Syndromes in a High Risk Population. AB - BACKGROUND: It is unclear whether diagnostic protocols based on cardiac markers to identify low-risk chest pain patients suitable for early release from the emergency department can be applied to patients older than 65 years or with traditional cardiac risk factors. METHODS AND RESULTS: In a single-center retrospective study of 231 consecutive patients with high-risk factor burden in which a first cardiac troponin (cTn) level was measured in the emergency department and a second cTn sample was drawn 4 to 14 hours later, we compared the performance of a modified 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Using Contemporary Troponins as the Only Biomarker (ADAPT) rule to a new risk classification scheme that identifies patients as low risk if they have no known coronary artery disease, a nonischemic electrocardiogram, and 2 cTn levels below the assay's limit of detection. Demographic and outcome data were abstracted through chart review. The median age of our population was 64 years, and 75% had Thrombosis In Myocardial Infarction risk score >=2. Using our risk classification rule, 53 (23%) patients were low risk with a negative predictive value for 30-day cardiac events of 98%. Applying a modified ADAPT rule to our cohort, 18 (8%) patients were identified as low risk with a negative predictive value of 100%. In a sensitivity analysis, the negative predictive value of our risk algorithm did not change when we relied only on undetectable baseline cTn and eliminated the second cTn assessment. CONCLUSIONS: If confirmed in prospective studies, this less-restrictive risk classification strategy could be used to safely identify chest pain patients with more traditional cardiac risk factors for early emergency department release. PMID- 26667087 TI - Comparison of Approaches to Revascularization in Patients With Multivessel Coronary Artery Disease Presenting With ST-Segment Elevation Myocardial Infarction: Meta-analyses of Randomized Control Trials. AB - BACKGROUND: Significant controversy exists regarding the best approach for nonculprit vessel revascularization in patients with multivessel coronary artery disease presenting with ST-segment elevation myocardial infarction. We conducted a systematic investigation to pool data from current randomized controlled trials (RCTs) to assess optimal treatment strategies in this patient population. METHODS AND RESULTS: A comprehensive search of SCOPUS from inception through May 2015 was performed using predefined criteria. We compared efficacy and safety outcomes of different approaches by categorizing the studies into 3 groups: (1) complete revascularization (CR) versus culprit lesion revascularization (CL) at index hospitalization, (2) CR at index hospitalization versus staged revascularization (SR) of nonculprit vessels at a separate hospitalization, and (3) comparison of SR versus CL. Eight eligible RCTs met the inclusion criteria: (1) CR versus CL (6 RCTs, n=1727) (2) CR versus SR (3 RCTs, n=311), and (3) SR versus CL (1 RCT, n=149). We observed significantly lower rates of major adverse cardiovascular events, revascularization, and repeat percutaneous coronary interventions among patients treated with CR and SR compared with a CL approach (P<0.05). The rates of all-cause mortality, cause-specific mortality, major bleeding, reinfarction, stroke, and contrast-induced nephropathy did not differ in the CR arm compared with the CL arm. The rates of these outcomes were similar in the CR and SR arms. CONCLUSION: Results suggest that CR and SR compared with CL reduce major adverse cardiovascular event and revascularization rates primarily by lowering repeated percutaneous coronary intervention rates. We did not observe any increase in the rate of adverse events while using a CR or SR strategy compared with a CL approach. Current guidelines discouraging CR need to be reevaluated, and clinical judgment should prevail in treating multivessel coronary artery disease patients with ST-segment elevation myocardial infarction as data from larger RCTs accumulate. PMID- 26667088 TI - Advanced age is a risk factor for proximal adenoma recurrence following colonoscopy and polypectomy. AB - BACKGROUND: Knowledge of risk factors for recurrence of colorectal adenomas may identify patients who could benefit from individual surveillance strategies. The aim of this study was to identify risk factors for recurrence of colorectal adenomas in a high-risk population. METHODS: Data were used from a randomized clinical trial that showed no effect of aspirin-calcitriol-calcium treatment on colorectal adenoma recurrence. Patients at high risk of colorectal cancer who had one or more sporadic colorectal adenomas removed during colonoscopy were followed up for 3 years. Independent risk factors associated with recurrence and characteristics of recurrent adenomas were investigated in a generalized linear model. RESULTS: After 3 years, the recurrence rate was 25.8 per cent in 427 patients. For younger subjects (aged 50 years or less), the recurrence rate was 19 per cent; 18 of 20 recurrent adenomas were located in the distal part of the colon. For older subjects (aged over 70 years), the recurrence rate was 35 per cent, and 16 of 25 recurrent adenomas were in the proximal colon. Age (odds ratio (OR) 1.04, 95 per cent c.i. 1.01 to 1.07) and number of adenomas (OR 1.27, 1.11 to 1.46) at the time of inclusion in the study were independent risk factors for recurrence. CONCLUSION: In contrast to current guidelines, advanced age is not a reason to discontinue adenoma surveillance in patients with an anticipated live expectancy in which recurrence can arise. PMID- 26667089 TI - Urinary protein-to-creatinine ratio in pregnant women after dipstick testing: prospective observational study. AB - BACKGROUND: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. METHODS: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. RESULTS: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and >= 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 + . CONCLUSIONS: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with >= 1+ as well as normotensive women with >= 2+ on dipstick test should be advised to undergo the P/Cr test. PMID- 26667090 TI - Simultaneous determination of antimony and boron in beverage and dairy products by flame atomic absorption spectrometry after separation and pre-concentration by cloud-point extraction. AB - A new cloud-point extraction (CPE) method was developed for the pre-concentration and simultaneous determination of Sb(III) and B(III) by flame atomic absorption spectrometry (FAAS). The method was based on complexation of Sb(III) and B(III) with azomethine-H in the presence of cetylpyridinium chloride (CPC) as a signal enhancing agent, and then extraction into the micellar phase of Triton X-114. Under optimised conditions, linear calibration was obtained for Sb(III) and B(III) in the concentration ranges of 0.5-180 and 2.5-600 MUg l(-1) with LODs of 0.15 and 0.75 MUg l(-1), respectively. Relative standard deviations (RSDs) (25 and 100 MUg l(-1) of Sb(III) and B(III), n = 6) were in a range of 2.1-3.8% and 1.9-2.3%, respectively. Recoveries of spiked samples of Sb(III) and B(III) were in the range of 98-103% and 99-102%, respectively. Measured values for Sb and B in three standard reference materials were within the 95% confidence limit of the certified values. Also, the method was used for the speciation of inorganic antimony. Sb(III), Sb(V) and total Sb were measured in the presence of excess boron before and after pre-reduction with an acidic mixture of KI-ascorbic acid. The method was successfully applied to the simultaneous determination of total Sb and B in selected beverage and dairy products. PMID- 26667091 TI - Genome-wide association study reveals regions associated with gestation length in two pig populations. AB - Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE. PMID- 26667092 TI - Highly sensitive electrochemical immunosensor for IgG detection based on optimized rigid biocomposites. AB - In this work we present the construction of immunosensors based on graphite-epoxy which incorporate RIgG to the composite matrix. In order to improve the electrochemical properties of the immunocomposite electrodes, characterization and optimization was carried out in terms of electrochemical impedance spectroscopy and cyclic voltammetry. Consequently, taking into the account the properties required by a sensitive electrode such as high electron-transfer rate, high signal-to-noise ratio and suitable sensitivity; the optimal proportion of the transducer material (graphite-epoxy ratio) was chosen using constant amount of RIgG. The optimum composition range values, which provide these requirements, were from 16% to 17% of graphite loading. Then, the analytical properties of these immunosensors were evaluated measuring RIgG by using a competitive assay and using alkaline phosphatase-labeled antibody. Amperometric measurements were performed using hydrogen peroxide as substrate. Moreover, it has been the first time that it has been performed an optimization of the antigen-antibody ratio used in the assay, being this reduced significantly. PMID- 26667093 TI - Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding. AB - Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5mm in diameter, 25.5mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding. PMID- 26667094 TI - The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies. AB - INTRODUCTION: The urokinase plasminogen activator (uPA) system, comprising the serine protease uPA, its cognate receptor, uPAR, and two endogenous inhibitors, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2), is a key player in the break-down of extracellular matrix (ECM) and basement membrane. Elevated expression of uPA and uPAR is observed in numerous cancer types and associated with poor prognosis. AREAS COVERED: In addition to the aberrant expression during tumor development, the components of uPA system are functionally involved in various processes that are prerequisite for cancer progression. These processes include, but not limited to, ECM degradation, angiogenesis, cell proliferation, adhesion, migration and epithelial-mesenchymal transition. All of these findings implicate uPA system as a target for cancer treatment. Thus, therapeutic agents and approaches to targeting the constituents of uPA system, mainly at their expression level and biological activities, have been extensively used in antineoplastic investigations. EXPERT OPINION: Because of promising results obtained from previous preclinical studies, several clinical trials aimed at inhibiting the expression or function of uPA/uPAR have been completed or are ongoing. In these trials, favorable outcomes in reducing metastatic spread and extending the lifespan of cancer patients have been reported, and no severe adverse events were observed. PMID- 26667095 TI - Religion, coping and outcome in out-patients with depression or diabetes mellitus. AB - OBJECTIVE: The study assesses the association between religiosity and coping style with the outcome of depression and diabetes. METHOD: Using a simple random sampling, we recruited 112 participants with diabetes and an equal number with depression consecutively, matching for gender. Religiosity was determined using Religious Orientation Scale (revised) (ROS-R), coping styles with Brief Religious Coping (Brief RCOPE) scale and Mental Adjustment to Cancer (MAC) scale (adapted). Primary and secondary outcomes were evaluated using Sheehan's Disability Scale (SDS) and Becks Depression Inventory-II (BDI-II) respectively. RESULTS: Among participants with diabetes, BDI-II total scores correlated negatively with ROS-R Extrinsic Social (r = -0.2, P < 0.05) and Fighting Spirit (r = -0.3, P < 0.05) but correlated positively with Helplessness/Hopelessness (r = 0.3, P < 0.05) and Brief RCOPE Negative (r = 0.4, P < 0.05). SDS global scores correlated positively with Helplessness/Hopelessness (r = 0.3, P < 0.05) and Brief RCOPE Negative (r = 0.4, P < 0.05). Among participants with depression, BDI-II total scores correlated negatively with Intrinsic religiosity (r = -0.2, P < 0.05) and Fighting Spirit (r = -0.4, P < 0.05) but correlated positively with Helplessness/Hopelessness (r = 0.6, P < 0.05) and Brief RCOPE Negative (r = 0.7, P < 0.05). SDS global scores correlated negatively with Intrinsic religiosity (r = -0.2, P < 0.05) and Fighting Spirit (r = -0.3, P < 0.05) but correlated positively with Helplessness/Hopelessness (r = 0.5, P < 0.05) and Brief RCOPE Negative (r = 0.4, P < 0.05). CONCLUSION: High intrinsic and extrinsic religiosities are likely to be associated with positive coping skills and better treatment outcome in patients with depression or diabetes. PMID- 26667096 TI - Sexuality Assessment Knowledge, Attitude, and Skill of Nursing Students: An Experimental Study with Control Group. AB - PURPOSE: The purpose of this study was to determine sexuality assessment knowledge, attitude, and skill of student nurses before and after sexuality training. METHODS: This study was conducted experimentally in a model with a pretest to posttest control group. FINDINGS: In the measurements made after training, it was observed that mean scores of Sexuality Assessment Information Test, Sexual Attitude and Beliefs Scale, and Sexuality Assessment Skills Check List in the experimental group were significantly higher than mean scores of students in the control group (p < .05). CONCLUSION: It was determined that sexuality assessment skills training has a positive effect on the knowledge, attitude, and behavior of nursing students. PRACTICE IMPLICATIONS: Sexuality assessment skills training can provide nurses with a guide for discussing the topic of sexual health with their patients. PMID- 26667097 TI - Immediate dental implant placement into infected vs. non-infected sockets: a meta analysis. AB - OBJECTIVE: This meta-analysis was aimed at assessing whether immediate dental implant placement into infected vs. non-infected sites produced different effects on implant failure risk and marginal bone loss. MATERIAL AND METHODS: Relevant studies were identified by searching articles in PubMed, Web of Knowledge, and the Cochrane Library through February 2015 and by reviewing the reference lists of the retrieved articles. When an intervention led to dichotomous outcomes, the outcomes were expressed as risk ratios, whereas continuous outcomes were expressed as mean differences in millimeters; each had a 95% confidence interval. Study-specific estimates were combined using fixed-effects models. RESULTS: A total of 1743 articles were identified following the search process. Seven studies were finally included in the meta-analysis, which comprised a total of 1586 implants and 25 failures. Compared to the immediate insertion of a dental implant into a non-infected site, the insertion of an implant into an infected site showed 116% increase in the risk of implant failure, which had borderline statistical significance (risk ratio = 2.16, 95% confidence interval: 0.97, 4.80, P = 0.058; heterogeneity: I2 = 0.0%, Pheterogeneity = 0.997). With regard to marginal bone loss, we observed no statistically significant difference between insertions into infected vs. non-infected sites (mean difference = -0.04, 95% confidence interval: -0.09, 0.02, P = 0.173, heterogeneity: I2 = 0.0%, Pheterogeneity = 0.765). CONCLUSION: This meta-analysis suggests that immediately placing a dental implant into an infected site may increase the risk of implant failure. Given the presence of uncontrolled confounders in the studies that were assessed, the results should be interpreted with caution. PMID- 26667098 TI - Cardiovascular Implications of Hypoglycemia in Diabetes Mellitus. PMID- 26667100 TI - A Case of Penetrating Atherosclerotic Ulcer Treated With Thoracic Endovascular Aortic Repair. PMID- 26667101 TI - Three Recurrent Episodes of Apical-Ballooning Takotsubo Cardiomyopathy in a Man. PMID- 26667102 TI - Letter by Ayoub Regarding Article, "Prospective Randomized Trial of Moderately Strenuous Aerobic Exercise After an Implantable Cardioverter Defibrillator". PMID- 26667103 TI - Response to Letter Regarding Article, "Prospective Randomized Trial of Moderately Strenuous Aerobic Exercise After an Implantable Cardioverter Defibrillator". PMID- 26667104 TI - Letter by Ortega-Paz et al Regarding Article, "East Asian Variant of Aldehyde Dehydrogenase 2 Is Associated With Coronary Spastic Angina: Possible Roles of Reactive Aldehydes and Implications of Alcohol Flushing Syndrome". PMID- 26667106 TI - Correction. PMID- 26667105 TI - Response to Letter Regarding Article, "East Asian Variant of Aldehyde Dehydrogenase 2 Is Associated With Coronary Spastic Angina: Possible Roles of Reactive Aldehydes and Implications of Alcohol Flushing Syndrome". PMID- 26667107 TI - A randomized trial comparing two approaches to weight loss. AB - Weight loss programs evidence considerable variability in treatment outcomes, and weight regain is common, signaling the need for the refinement of effective treatments. This study compared the recently developed Transforming Your Life program to the Diabetes Prevention Program, considered the "Gold Standard" in behavioral weight loss treatment. A total of 98 participants (Transforming Your Life = 51; Diabetes Prevention Program = 47) were randomized to the two weight loss interventions. The Transforming Your Life program and Diabetes Prevention Program produced comparable weight loss and maintenance outcomes. Individuals may benefit from engagement in the Transforming Your Life program, if they are searching for a somewhat novel approach to losing weight other than that offered by the Diabetes Prevention Program. PMID- 26667108 TI - A preclinical dental trauma teaching module. AB - A dental trauma exercise using the anterior segment of a sheep mandible as a model has been incorporated into the undergraduate dental programme at the University of Adelaide since 2011. Students are required to replant a simulated tooth avulsion, reposition a laterally luxated tooth injury and then apply a flexible splint consisting of 40 lb fishing nylon attached with a resin-modified glass ionomer cement, GC Fuji Ortho LC. The exercise concludes with the simple removal of the splint with a spoon excavator. The acrylic mounted formalin-fixed sheep mandible is reusable, which has obvious economic and practical advantages. PMID- 26667109 TI - Relationship between immune function recovery and infectious complications in patients following living donor liver transplantation. AB - AIM: The ImmuKnow (IK) assay enables the evaluation of peripheral blood CD4(+) adenosine triphosphate activity to facilitate an objective assessment of the cellular immune function in immunosuppressed patients. However, it is unclear whether the IK assay is utilized during the acute postoperative periods following living donor liver transplantation (LDLT). METHODS: The IK values of 43 LDLT recipients were measured during the month following LDLT to evaluate the relationship between the measured IK values and infectious events. RESULTS: The IK values after LDLT were significantly increased compared with the IK values before LDLT ( P < 0.01). During the month following transplantation, the rate of bacterial infection in the recipients with IK values of more than 225 ng/mL was significantly lower than that in the recipients with IK values of 225 ng/mL or less ( 42.1% vs 91.7%, respectively; P < 0.01). The rate of severe infections among the recipients who maintained IK values of more than 150 ng/mL was significantly lower than that among the recipients with IK values of 150 ng/mL or less during the month following transplantation ( 3.7% vs 56.3%, respectively; P < 0.01). CONCLUSION: The immune system of LDLT recipients dramatically improved following transplantation. The IK values of LDLT recipients were associated with the incidence of infectious events during the perioperative period after LDLT. Monitoring IK values was useful during both the acute and long-term postoperative periods. PMID- 26667111 TI - [In Process Citation]. AB - Approximately 70.000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy on one hand. From socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Available since 2003 in Hungary, pegylated interferon + ribavirin dual therapy can clear the virus in 40-45% of previously not treated (naive), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained virologic response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and or fibrosis in the liver. Non-invasive methods (eleastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations tharpy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost effective combinations based on the cost per sustained virologic response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 2), 3-24. PMID- 26667110 TI - Promoting healthful family meals to prevent obesity: HOME Plus, a randomized controlled trial. AB - BACKGROUND: Family meal frequency has been shown to be strongly associated with better dietary intake; however, associations with weight status have been mixed. Family meals-focused randomized controlled trials with weight outcomes have not been previously conducted. Therefore, this study purpose was to describe weight related outcomes of the HOME Plus study, the first family meals-focused randomized controlled trial to prevent excess weight gain among youth. METHODS: Families (n = 160 8-12-year-old children and their parents/guardians) were randomized to intervention (n = 81) or control (n = 79) groups. Data were collected at baseline (2011-2012), post-intervention (12-months post-baseline) and follow-up (21-months post-baseline). The intervention included ten monthly group sessions (nutrition education; hands-on meal and snack planning, preparation, and skill development; screen time reductions) and five motivational, goal-setting phone calls. The main outcome was child body mass index (BMI) z-score. RESULTS: General linear models, adjusted for baseline values and demographics, showed no significant treatment group differences in BMI z scores at post-intervention or follow-up; however, a promising reduction in excess weight gain was observed. Post-hoc stratification by pubertal onset indicated prepubescent children in the intervention group had significantly lower BMI z-scores than their control group counterparts. CONCLUSIONS: The study used a strong theoretical framework, rigorous design, quality measurement and a program with high fidelity to test a family meals-focused obesity prevention intervention. It showed a modest decrease in excess weight gain. The significant intervention effect among prepubescent children suggests the intervention may be more efficacious among relatively young children, although more research with appropriately powered samples are needed to replicate this finding. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01538615. Registered 01/17/2012. PMID- 26667112 TI - [In Process Citation]. AB - Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2016 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous ente- cavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2015, 156(Suppl. 2) 25-36. PMID- 26667113 TI - Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis. AB - Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 MUg/mL and 4.9 MUg/mL.h, respectively; and for symptomatic animals 3.2 MUg/mL and 17.3 MUg/mL.h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 MUg/mL and the AUC0-8 h was 25.8 MUg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 MUg/mL; mean AUC0-8 h : 18.1 MUg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 MUg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly. PMID- 26667115 TI - Recognizing and reporting domestic violence: attitudes, experiences and behavior of Dutch dentists. AB - BACKGROUND: On July 1(st) 2013 the Mandatory Reporting Code Act came into force in the Netherlands, making it compulsory for health professionals to adhere to a reporting code when they suspect patients to be victims of domestic violence (DV) or child abuse (CA). The Royal Dutch Dental Association (KNMT) developed a reporting code for dental professionals (RCD). Moreover, an e-learning module about DV has been developed. A web-survey was conducted to investigate how general dental practitioners (GDPs) deal with the RCD and what their experiences are with (signs of) DV and CA. METHODS: In April 2014 1038 GDPs were invited by e mail to participate in a web-survey consisting of 24 items, through the KNMT Data Stations Project. The data was analyzed using SPSS (RELIABILITY, CHISQ and ANOVA). RESULTS: Of all GDPs invited to participate 264 (25 %) responded. 82 % of these GDPs are aware of their obligation to use the reporting code. 54 % of the GDPs are in favor of this obligation. 76 % of the GDPs have taken notice of the KNMT's RCD and 51 % of the GDPs have implemented the reporting code in one form or another in their practice. 24 % of the GDPs stated having suspected DV during the last twelve months in the case of 2.4 patients on average. 81 % took note of this in the patient's record and 58 % also took action in different ways. 54 % wants to complete the e-learning module. CONCLUSIONS: Most GDPs are aware of the new legislation and have taken cognizance of the RCD. Even though the majority of GDPs are not opposed to using a reporting code, over half of them have not yet implemented the code in practice. An important factor in this regard seems to be that a substantial minority of the GDPs says they are not sufficiently informed about aspects of reporting a case and about the steps they have to take. PMID- 26667116 TI - Studies on Chloride Channels and their Modulators. AB - The prime roles of mutations in the genes, encoding chloride ion channels, in various human diseases of muscle, kidney, bone and brain, such as congenital myotonia, myotonic dystrophy, cystic fibrosis, osteopetrosis, epilepsy, glioma, etc., have been well established. Chloride ion channels are also responsible for glioma progression in brain and malaria parasite in red blood cells. The present article thus emphasises on the various diseases associated with chloride channel regulation and their modulators. Studies on various chloride channels and their modulators have been discussed in detail. PMID- 26667117 TI - HCN Channel as Therapeutic Targets for Heart Failure and Pain. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles both in the control of heart rate and neuronal excitability. HCN channels open on hyperpolarization voltage, permeate to potassium and sodium, and generate an inward current, which is modulated by intracellular cAMP. HCN channels have been reported to involve in various human diseases, including heart failure, pain and epilepsy with datas from mutagenesis, transgenic mice and pharmacological studies. As a result, HCN channels may offer excellent drug development opportunities for novel analgestic, bradycardic and anticonvulsant drugs. Ivabradine is the first HCN channel inhibitor being clinically approved in 2005 for the treatment of chronic stable angina pectoris and heart failure. This review will summarize the structure and function of HCN channels. Further, we will discuss recent advances concerning the identification and action mechanism of reported HCN channel inhibitors. PMID- 26667118 TI - Restorative Outcomes of a Minimally Invasive Restorative Approach Based on Atraumatic Restorative Treatment to Manage Early Childhood Caries: A Randomised Controlled Trial. AB - A pragmatic randomised controlled trial comparing a minimally invasive approach based on atraumatic restorative treatment (ART) procedures (test) was tested against the standard-care approach (control) to treat early childhood caries (ECC) in a primary-care setting in Perth, W.A., Australia. Parent/child dyads with ECC were allocated to the test or control group using stratified block randomisation. Children were examined at baseline and follow-up by two calibrated examiners blinded to group allocation status. Dental therapists trained in ART provided treatment to the test group and dentists treated the control group. Restoration quality was evaluated at follow-up using the ART criteria. Data were analysed on an intention-to-treat basis; test of proportions, Wilcoxon rank test and logistic regression, controlling for clustering of teeth, were used. Two hundred and fifty-four children were randomised (test = 127 and control = 127). There was no statistically significant difference in age, sex and baseline caries experience between the test and control groups. At follow-up (mean interval 11.4 months, SD 3.1), 220 children were examined (test = 115 and control = 105) and 597 teeth (test = 417 and control = 180) were evaluated for restoration quality, of which 16.8% (test) and 6.7% (control) were judged to have failed (required replacement; p < 0.01). Intention-to-treat, multiple logistic regression found multisurface restorations (OR = 10.4) had significantly higher odds of failure, while referral for specialist paediatric care had significantly lower odds of restoration failure (OR = 0.2). The ART-based approach enabled more children and teeth to be treated, and multisurface restoration and treatment in a primary-care setting had higher odds of restoration failure. PMID- 26667114 TI - Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges. AB - Huntington's disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD. PMID- 26667120 TI - Food structure is critical for optimal health. AB - Much nutrition policy is nutrient-based, supported by extensive nutrient science and food nutrient composition tables and recommendations for dietary evaluation. There are no comparable instruments for food structure. This constitutes a policy and practice gap since food is valued for its textural properties and not simply its chemistry. The structurally-important 'dietary fibre' at first proved of greater interest for its chemistry than its physico-chemistry even to health scientists and workers. As food chemistry became evidently complex, especially for phytonutrients, food-based dietary guidelines became an imperative and were launched by FAO and WHO in Cyprus in 1995. Food-health relationships, after weaning, are best articulated in terms of the achievement of dietary diversity, predicated partly on how intact foods are or in what way they are prepared. Cooking itself has health-promoting characteristics. Even with identical chemistry, food structure makes a major difference to biological and health outcomes. With evidence that food structure contributes to the matrix that food provides for nutrient delivery, and also to gut microbiomic profile and integrity, concern has grown about overly-processed food and health outcomes. The definition and categorisation of 'ultra-processed foods' is now a work-in progress. Future public health nutritional and clinical nutrition developments will take account of food structure. To these ends, food composition tables will need to provide information like particle size and viscosity. Dietary recommendations will need to take account of food structure, as is the case for Brazil whose first step is "Make natural or minimally processed foods the basis of your diet". PMID- 26667119 TI - Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring. AB - The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes. PMID- 26667121 TI - Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels. AB - BACKGROUND: Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. MATERIALS AND METHODS: A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin like growth factor-1 levels. RESULTS: H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 +/- 2.26 vs 9.53 +/- 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori seropositive children (-0.33 +/- 1.08 vs 0.04 +/- 1.26, p = .044 and 0.13 +/- 0.92 vs 0.23 +/- 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 +/- 753.0 vs 2808.3 +/- 911.4 pg/mL, p = .06; 470 +/- 176 vs 521 +/- 179 ng/mL, p = .32, respectively). CONCLUSIONS: Children infected with H. pylori are prone to short stature. This effect seems to be independent of neuroendocrine hormones. PMID- 26667123 TI - [Frailty in Germany: status and perspectives : Results from a workshop of the German Society for Epidemiology]. AB - BACKGROUND: A standardized, valid and comparable operationalization and assessment of frailty in population-based studies is essential in order to describe the prevalence and determinants of frailty in the population. AIM: After an introduction to the subject the main goal of a workshop at the 9th annual meeting of the German Society for Epidemiology (DGEpi) was to present approaches and results from four different studies in Germany. MATERIAL AND METHODS: The following four population-based studies were used to describe frailty in Germany: the German health interview and examination survey for adults (DEGS1), the epidemiological study on the chances of prevention, early recognition and optimized treatment of chronic diseases in the older population (ESTHER), the cooperative health research in the region Augsburg (KORA Age) study and the longitudinal urban cohort ageing study (LUCAS) in Hamburg. RESULTS: The four studies consistently showed that frailty is widespread in older and oldest-old persons in Germany. It is obvious that frailty represents a relevant concept in Germany even if there is currently no uniform basis for operationalization. CONCLUSION: Concepts and instruments for the collation of frailty should be included in future population-based studies in order to make a better assessment of older people's health situation and to describe the unused potential for prevention in an aging society. PMID- 26667125 TI - [Potential of cooperative learning in project development : Relevance of cooperative participation procedure for the further development of generation appropriate accomodation in structurally weak rural areas]. AB - BACKGROUND: A joint initiative of existing senior care organizations, the municipality of Meyenburg and the state of Brandenburg was further developed by affiliation of an institute of the Brandenburg University of Technology Cottbus Senftenberg (ABV) in cooperation with members of the architecture and social work departments in 2014. MATERIAL AND METHODS: A cooperative process between different players was central to create an appropriate structure of services for this region. RESULTS: Cooperative projects are necessary to establish new forms of generation-appropriate living and care concepts in rural areas. CONCLUSION: Cooperative learning methods are needed to develop new forms of generation appropriate living and care concepts in rural areas, which take the diversity of elderly people, the rural context, intergenerational residential arrangements and affordable accommodation that meets the requirements of the social security system into account. Furthermore, the project had to reflect the recent developments of the German care insurance. The article describes the participatory methods, the coordination process and the resulting concept. PMID- 26667126 TI - [Users and utilization of support groups among caregivers of dementia patients : Results of a naturalistic observational study]. AB - BACKGROUND: Caring for patients with Alzheimer's disease (AD) is frequently associated with an increased burden for the caregiving relatives (CG). While therapeutic options and low threshold assistance offers for a reduction of the burden have become well established, data on the utilization of support groups (SG) are still lacking. MATERIAL AND METHODS: In the outpatient neurological and psychiatric routine treatment, AD patients were enrolled with their accompanying CG in a 2-stage study. Firstly, each patient was clinically documented by the treating physician and each CG was asked to fill out a questionnaire on the current care situation at the patient's home. In stage two, each CG was additionally assessed with a standardized interview and screened for depression with the depression screening questionnaire (DSQ). Each CG also rated the current CG burden, life satisfaction and health condition on a visual analogue scale (VAS). RESULTS: Overall, 14.8 % of CGs attended an SG. The CGs who visited an SG showed a tendency to report a severe CG burden more often than CGs who did not (71.9 % vs. 56.3 %, p = 0.060) and more frequently a lower satisfaction with life (33.3 vs. 17.2 %, p < 0.01). They also reported higher rates of verbal and physical aggression by the patients (51.5 % vs. 34.0 %, p < 0.05 and 39.4 % vs. 12.7 %, p < 0.01, respectively) and appraised their health condition to be lower (VAS score 66.0 % vs. 54.0, p < 0.01). Depressive disorders occurred in both groups at similar rates (54.1 % and 42.1 %, p = 0.317). CONCLUSION: The data suggest that the decision to join an SG is influenced more by behavioral and non cognitive symptoms of the AD rather than its duration or severity. PMID- 26667127 TI - The increase in the number of spines on the gonadotropin-releasing hormone neuron across pubertal development in rats. AB - The onset of puberty is initiated by an increase in the release of the gonadotropin-releasing hormone (GnRH) from GnRH neurons in the hypothalamus. However, the precise mechanism that leads to the activation of GnRH neurons at puberty remains controversial. Spines are small protrusions on the surface of dendrites that normally receive excitatory inputs. In this study, we analyzed the number and morphology of spines on GnRH neurons to investigate changes in synaptic inputs across puberty in rats. For morphological estimation, we measured the diameter of the head (DH) of each spine and classified them into small-type (DH < 0.65 MUm), large-type (DH > 0.65 MUm) and giant-type (DH > 0.9 MUm). The greatest number of spines was observed at the proximal dendrite within 50 MUm of the soma. At the soma and proximal dendrite, the number of spines was greater in adults than in juveniles in both male and female individuals. Classification of spines revealed that the increase in spine number was due to increases in large- and giant-type spines. To further explore the relationship between spines on GnRH neurons and pubertal development, we next analyzed adult rats neonatally exposed to estradiol benzoate, in which puberty onset and reproductive functions are disrupted. We found a decrease in the number of all types of spines. These results suggest that GnRH neurons become to receive more and greater excitatory inputs on the soma and proximal dendrites as a result of the changes that occur at puberty and that alteration to spines plays a pivotal role in normal pubertal development. PMID- 26667128 TI - Presynaptic protein Synaptotagmin1 regulates the neuronal polarity and axon differentiation in cultured hippocampal neurons. AB - BACKGROUND: Hippocampal neurons in the brain polarize to form multiple dendrites and one long axon. The formation of central synapses remains poorly understood. Although several of the intracellular proteins involved in the clustering of central neurotransmitter receptors and ion channels have been identified, the signals involved in pre- and postsynaptic differentiation remain elusive. Synaptotagmin1 is an abundant and important presynaptic vesicle protein that binds Ca(2+) (J Biol Chem 277:7629-7632, 2002) in regulation of synaptic vesicle exocytosis at the synapse. Synapse consists of the formation of synaptic connections and requires precise coordination of Synaptotagmin1. It was reported Synaptotagmin1 plays an important roles in the formation of axonal filopodia and branches in chicken forebrain neurons (Dev Neurobiol 73:27-44, 2013). To determine if Synaptotagmin1 could have a role in formation of axon in hippocampal neurons, we investigated the effects of Synaptotagmin1 overexpression and knockdown using the shRNA on the growth and branching of the axons of primary hippocampal neurons. We showed that overexpression of Synaptotagmin1 leads to abnormal multiple axon formation in cultured rat hippocampal neurons. RESULTS: We first examined the effects of Synaptotagmin1 on the numbers of axon and dendrites. We found that the overexpression of Synaptotagmin1 led to the formation of multiple axons and induced an increase in the number of endogenous postsynaptic protein Homer1c clusters in cultured hippocampal neurons. Endogenous initial segment of axon was detected with anti-sodium channel (anti-NaCh) antibody and with anti-Tau1 (J Neurosci 24: 4605-4613, 2004). The endogenous initial segment of axon was stained with anti-NaCh antibodies and with anti-Tau1 antibodies. Then the numbers of prominence dyed positive were counted as axon. We attempted to specifically knockdown the endogenous Synaptotagmin1 with small hairpin RNAs (shRNAs). To further dissect the functions of endogenous Synaptotagmin1 in neuronal polarity, we used the shRNA of Synaptotagmin1 that specifically blocks the existence of endogenous Synaptotagmin1. When the shRNA of Synaptotagmin1 was introduced to the cells, the number of axons and dendrites did not change. CONCLUSIONS: These results indicate that the accumulation of Synaptotagmin1 may play an important role in axon/dendrite differentiation. PMID- 26667129 TI - It Is Time to View Pregnancy as a Stress Test. PMID- 26667130 TI - Microarray: gateway to unravel the mystery of abiotic stresses in plants. AB - Environmental factors, such as drought, salinity, extreme temperature, ozone poisoning, metal toxicity etc., significantly affect crops. To study these factors and to design a possible remedy, biological experimental data concerning these crops requires the quantification of gene expression and comparative analyses at high throughput level. Development of microarrays is the platform to study the differential expression profiling of the targeted genes. This technology can be applied to gene expression studies, ranging from individual genes to whole genome level. It is now possible to perform the quantification of the differential expression of genes on a glass slide in a single experiment. This review documents recently published reports on the use of microarrays for the identification of genes in different plant species playing their role in different cellular networks under abiotic stresses. The regulation pattern of differentially-expressed genes, individually or in group form, may help us to study different pathways and functions at the cellular and molecular level. These studies can provide us with a lot of useful information to unravel the mystery of abiotic stresses in important crop plants. PMID- 26667131 TI - Synthesis of rosmarinic acid analogues in Escherichia coli. AB - OBJECTIVES: To produce rosmarinic acid analogues in the recombinant Escherichia coli BLRA1, harboring a 4-coumarate: CoA ligase from Arabidopsis thaliana (At4CL) and a rosmarinic acid synthase from Coleus blumei (CbRAS). RESULTS: Incubation of the recombinant E. coli strain BLRA1 with exogenously supplied phenyllactic acid (PL) and analogues as acceptor substrates, and coumaric acid and analogues as donor substrates led to production of 18 compounds, including 13 unnatural RA analogues. CONCLUSION: This work demonstrates the viability of synthesizing a broad range of rosmarinic acid analogues in E. coli, and sheds new light on the substrate specificity of CbRAS. PMID- 26667132 TI - The use of chitooligosaccharide in beer brewing for protection against beer spoilage bacteria and its influence on beer performance. AB - OBJECTIVES: To identify a biological preservative that can protect beer from microbial contamination, which often results in the production of turbidity and off-flavor. RESULTS: The antimicrobial activity of a chitooligosaccharide against beer-spoilage bacteria and its effect on the fermentation performance of brewer's yeast was studied. Chitooligosaccharide with an average 2 kDa molecular weight was the best at inhibiting all tested beer-spoilage bacteria. The application of chitooligosaccharide in the brewing process did not influence the fermentation of brewer's yeast. The change in beer performance induced by the contamination of Lactobacillus brevis could be effectively controlled by application of chitooligosaccharide in the beer brewing process. CONCLUSION: The experimental data suggested that chitooligosaccharide should be an excellent preservative to inhibit beer-spoilage bacteria in the brewing process and in the end product. PMID- 26667133 TI - Genome-wide identification of conserved microRNA and their response to drought stress in Dongxiang wild rice (Oryza rufipogon Griff.). AB - OBJECTIVES: To identify drought stress-responsive conserved microRNA (miRNA) from Dongxiang wild rice (Oryza rufipogon Griff., DXWR) on a genome-wide scale, high throughput sequencing technology was used to sequence libraries of DXWR samples, treated with and without drought stress. RESULTS: 505 conserved miRNAs corresponding to 215 families were identified. 17 were significantly down regulated and 16 were up-regulated under drought stress. Stem-loop qRT-PCR revealed the same expression patterns as high-throughput sequencing, suggesting the accuracy of the sequencing result was high. Potential target genes of the drought-responsive miRNA were predicted to be involved in diverse biological processes. Furthermore, 16 miRNA families were first identified to be involved in drought stress response from plants. CONCLUSION: These results present a comprehensive view of the conserved miRNA and their expression patterns under drought stress for DXWR, which will provide valuable information and sequence resources for future basis studies. PMID- 26667134 TI - Oesophageal spasm, vomiting and hyoscine hydrobromide patch. AB - We report the case of a 60-year-old woman with metastatic breast cancer whose intractable nausea and vomiting were effectively managed with a hyoscine hydrobromide (scopolamine) patch. Contrast swallow revealed oesophageal spasm to be the underlying cause. Symptom relief may be attributed to the antimuscarinic properties of the patch, allowing lower oesophageal sphincter relaxation. Following patch use she was able to enjoy small meals and fluids without symptoms. This is the first time this mechanism of action of scopolamine for alleviating nausea and vomiting has been described in the literature. PMID- 26667138 TI - Point/Counterpoint: Is stereotactic radiosurgery needed following resection of brain metastasis? PMID- 26667139 TI - Insulin-like growth factor 1 receptor signaling via Akt: a general therapeutic target in neurocutaneous melanocytosis? PMID- 26667140 TI - Response to "Insulin-like growth factor 1 receptor signaling via Akt: a general therapeutic target in neurocutaneous melanocytosis?". PMID- 26667142 TI - Molecular characterization and functional analysis of the GATA4 in tongue sole (Cynoglossus semilaevis). AB - The GATA family of transcription factors is characterized by two zinc finger domains and is involved in different cellular processes. GATA4 is a highly conserved transcription factor that regulates embryonic morphogenesis and cellular differentiation. GATA4 in vertebrates regulates its target genes to influence genital ridge differentiation. In this study, the GATA4 from tongue sole (Cynoglossus semilaevis) was characterized to understand the function of this transcription factor in sex differentiation. The full-length cDNA of C. semilaevis GATA4 comprised 2031bp, encoding a predicted polypeptide consisting of 402 amino acids with two conserved zinc finger domains. Phylogenetic, gene structure, and synteny analyses showed that C. semilaevis GATA4 was homologous to tetrapod GATA4. The mRNA transcript of C. semilaevis GATA4 exhibited high expression in the heart, liver, and gonad. GATA4 expression is dimorphic in the male and female gonads. Embryonic development expression profiles revealed the possible involvement of C. semilaevis GATA4 in morphogenesis. In situ hybridization results showed strong GATA4 signals in the spermatogonia and spermatocytes of the testis and in the oogonia, primary oocytes, and secondary oocytes of the ovary. The expression of C. semilaevis GATA4 in the male, pseudomale, and female gonads showed significantly different methylation levels of the two CpG sites (-2738 and -2647) among the three genders. Basing on these results, we speculated that GATA4 plays a potential role in sex differentiation. This study lays the groundwork for further sex control breeding techniques in C. semilaevis. PMID- 26667143 TI - CCL21-CCR7 promotes the lymph node metastasis of esophageal squamous cell carcinoma by up-regulating MUC1. AB - BACKGROUND: CCR7 and MUC1 are correlated with lymph node metastasis in ESCC, but the role of MUC1 in the CCR7-induced lymphatic metastasis and the underlying molecular mechanism is still unclear. METHODS: The expression of CCR7 and MUC1 was detected in the ESCC samples by IHC, and the clinical significance of CCR7 and MUC1 in ESCC was analyzed. The expression of CCR7 and MUC1 in ESCC cell lines was detected by qRT-PCR and western blot. The effect of CCL21 on the migration and invasion of ESCC cells was determined by transwell assay. The activity of MUC1 promoter was determined by luciferase reporter assay. The activation of Erk, Akt and Sp1 was detected by western blot and the binding of Sp1 to the MUC1 promoter was determined by ChIP. RESULTS: The co-expression of CCR7 and MUC1 was detected in 153 ESCC samples by IHC, and both were correlated with lymph node metastasis, regional lymphatic recurrence and poor prognosis. Correspondingly, increasing levels of MUC1 mRNA and protein were detected in the ESCC cell lines KYSE410 and Eca9706 after treatment with CCL21 in a time- and dose-dependent manner. Furthermore, silencing MUC1 could remarkably suppress the invasion and migration of ESCC cells induced by CCL21. Moreover, heterologous CCR7 promoted the invasion and migration of KYSE150 and up-regulated MUC1 expression. Increasing levels of activated ERK1/2 and Akt were detected in KYSE410 after treating the cells with CCL21, and inhibiting the activation of ERK1/2 but not Akt caused the increased transcription of MUC1. Finally, the phosphorylation of Sp1 induced by ERK1/2 and subsequent increases in the binding of Sp1 to the muc1 promoter at -99/-90 were confirmed to cause the up-regulation of MUC1 induced by CCL21-CCR7. CONCLUSIONS: Our findings suggested that MUC1 plays an important role in CCL21-CCR7-induced lymphatic metastasis and may serve as a therapeutic target in ESCC. PMID- 26667144 TI - A comparison of walk-in counselling and the wait list model for delivering counselling services. AB - BACKGROUND: Walk-in counselling has been used to reduce wait times but there are few controlled studies to compare outcomes between walk-in and the traditional model of service delivery. AIMS: To compare change in psychological distress by clients receiving services from two models of service delivery, a walk-in counselling model and a traditional counselling model involving a wait list. METHOD: Mixed-methods sequential explanatory design including quantitative comparison of groups with one pre-test and two follow-ups, and qualitative analysis of interviews with a sub-sample. Five-hundred and twenty-four participants >=16 years were recruited from two Family Counselling Agencies; the General Health Questionnaire-12 assessed change in psychological distress. RESULTS: Hierarchical linear modelling revealed clients of the walk-in model improved faster and were less distressed at the four-week follow-up compared to the traditional service delivery model. Ten weeks later, both groups had improved and were similar. Participants receiving instrumental services prior to baseline improved more slowly. The qualitative data confirmed participants highly valued the accessibility of the walk-in model, and were frustrated by the lengthy waits associated with the traditional model. CONCLUSIONS: This study improves methodologically on previous studies of walk-in counselling, an approach to service delivery not conducive to randomized controlled trials. PMID- 26667145 TI - The fundamentals of epidemiology and ethics in science. PMID- 26667146 TI - Use of (77)Se and (125)Te NMR Spectroscopy to Probe Covalency of the Actinide Chalcogen Bonding in [Th(En){N(SiMe3)2}3](-) (E = Se, Te; n = 1, 2) and Their Oxo Uranium(VI) Congeners. AB - Reaction of [Th(I)(NR2)3] (R = SiMe3) (1) with 1 equiv of either [K(18-crown 6)]2[Se4] or [K(18-crown-6)]2[Te2] affords the thorium dichalcogenides, [K(18 crown-6)][Th(eta(2)-E2)(NR2)3] (E = Se, 2; E = Te, 3), respectively. Removal of one chalcogen atom via reaction with Et3P, or Et3P and Hg, affords the monoselenide and monotelluride complexes of thorium, [K(18-crown-6)][Th(E)(NR2)3] (E = Se, 4; E = Te, 5), respectively. Both 4 and 5 were characterized by X-ray crystallography and were found to feature the shortest known Th-Se and Th-Te bond distances. The electronic structure and nature of the actinide-chalcogen bonds were investigated with (77)Se and (125)Te NMR spectroscopy accompanied by detailed quantum-chemical analysis. We also recorded the (77)Se NMR shift for a U(VI) oxo-selenido complex, [U(O)(Se)(NR2)3](-) (delta((77)Se) = 4905 ppm), which features the highest frequency (77)Se NMR shift yet reported, and expands the known (77)Se chemical shift range for diamagnetic substances from ~3300 ppm to almost 6000 ppm. Both (77)Se and (125)Te NMR chemical shifts of given chalcogenide ligands were identified as quantitative measures of the An-E bond covalency within an isoelectronic series and supported significant 5f-orbital participation in actinide-ligand bonding for uranium(VI) complexes in contrast to those involving thorium(IV). Moreover, X-ray diffraction studies together with NMR spectroscopic data and density functional theory (DFT) calculations provide convincing evidence for the actinide-chalcogen multiple bonding in the title complexes. Larger An-E covalency is observed in the [U(O)(E)(NR2)3](-) series, which decreases as the chalcogen atom becomes heavier. PMID- 26667148 TI - Are Children with Autism Spectrum Disorder Initially Attuned to Object Function Rather Than Shape for Word Learning? AB - We investigate the function bias--generalising words to objects with the same function--in typically developing (TD) children, children with autism spectrum disorder (ASD) and children with other developmental disorders. Across four trials, a novel object was named and its function was described and demonstrated. Children then selected the other referent from a shape match (same shape, different function) and function match (same function, different shape) object. TD children and children with ASD were 'function biased', although further investigation established that having a higher VMA facilitated function bias understanding in TD children, but having a lower VMA facilitated function bias understanding in children with ASD. This suggests that children with ASD are initially attuned to object function, not shape. PMID- 26667147 TI - Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum. AB - In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding. PMID- 26667149 TI - The Importance of Interviewing Adults on the Autism Spectrum About Their Depression and Suicidal Ideation Experiences. AB - This letter will summarise the current body of literature on adults with Asperger syndrome and their depression and suicidal ideation experiences. The purpose of this summary is to highlight the lack of published research on adults with Asperger syndrome or autism describing these experiences. PMID- 26667150 TI - Using study data to determine whether being sued for medical malpractice correlates with greater subsequent expenditure. PMID- 26667151 TI - Effects of aerobic interval training on measures of anxiety, depression and quality of life in patients with ischaemic heart failure and an implantable cardioverter defibrillator: A prospective non-randomized trial. AB - OBJECTIVE: To evaluate the short- and long-term effects of aerobic interval training on quality of life and on symptoms of anxiety and depression among patients with ischaemic heart failure and an implantable cardioverter defibrillator. DESIGN: Prospective, non-randomized controlled study. SUBJECTS: Patients with ischaemic heart failure and an implantable cardioverter defibrillator, willing to undergo an aerobic interval training programme. A total of 31 patients were enrolled (19 were assigned to the aerobic interval training group and 12 to the control group). METHODS: The aerobic interval training group performed a 12-week exercise training programme. All patients were evaluated with the Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS) and the International Physical Activity Questionnaire at baseline, after 12 weeks and at 2 years. RESULTS: The aerobic interval training group showed significant improvements in several SF-36 subscores at 12 weeks. There was an unadjusted significant reduction in the HADS depression (HADS-D) score. At follow-up, results in the aero-bic interval training group moved towards baseline or remained stable, whereas in the control group HADS-D scores and some SF-36 subscores deteriorated. CONCLUSION: Participation in a 12-week aerobic interval training programme resulted in significant improvements in several measures of quality of life and the unadjusted HADS-D score in patients with ischaemic heart failure with an implantable cardioverter defibrillator. At follow-up there was significantly less sedentary activity in the aerobic interval training group, while psychometric measures were no longer significantly different from baseline. PMID- 26667152 TI - Does meniscal pathology alter gait knee biomechanics and strength post-ACL reconstruction? AB - PURPOSE: Individuals following anterior cruciate ligament reconstruction (ACLR) with concomitant meniscal pathology have a higher risk of developing knee osteoarthritis (OA) compared to those with isolated ACLR. Knee extensor weakness and altered dynamic knee joint biomechanics have been suggested to play a role in the development of knee OA following ACLR. This study investigated whether these factors differ in people following ACLR who have concomitant meniscal pathology compared to patients with isolated ACLR. METHODS: Thirty-three patients with isolated ACLR and 34 patients with ACLR and meniscal pathology underwent strength and gait assessment 12-24 months post-operatively. Primary measures were peak isometric knee extensor torque and knee adduction moment (peak and impulse). Secondary measures included peak knee flexion moment and knee kinematics (sagittal and transverse). RESULTS: There were no between-group differences in knee extensor strength [mean difference (95 % CI) 0.09 (-0.23 to 0.42) Nm/kg, n.s.], peak knee adduction moment [-0.02 (-0.54 to 0.49) Nm/(BW * HT) %, n.s.] or knee adduction moment impulse [0.01 (-0.15 to 0.17) Nm/(BW * HT) %, p = n.s.]. No between-group differences were found for any secondary measures. CONCLUSIONS: No evidence was found to suggest that the higher prevalence of OA in patients with ACLR and meniscal pathology compared to patients with isolated ACLR is attributed to reduced knee muscle strength or altered knee joint biomechanics assessed 1-2 years post-surgery. Given that there is a higher incidence of knee OA in patients with concomitant meniscal pathology and ACLR, further investigation is needed so that population-specific rehabilitation protocols can be developed. LEVEL OF EVIDENCE: III. PMID- 26667154 TI - Evaluating the clinical significances of serum HE4 with CA125 in peritoneal tuberculosis and epithelial ovarian cancer. AB - This study aimed to evaluate the clinical significances of human epididymis protein 4 (HE4) with cancer antigen 125 (CA125) in differential diagnosis between epithelial ovarian cancer (EOC) and peritoneal tuberculosis (PTB). We retrospectively reviewed data of 31 patients suspected preoperatively as having EOC but whose pathological results revealed PTB. The concentrations of serum HE4 and CA125 in PTB were significantly lower than that in EOC. The optimal cutoffs to differentiate EOC from PTB were HE4 > 151.4 pmol/l and CA125 > 563.5 U/ml, which means EOC may be considered if HE4 or CA125 was greater than the cutoff, otherwise, PTB should not be neglected. Furthermore, the specificity and accuracy for differentiating PTB form EOC could be improved when combination HE4 and CA125. Conclusively, the combination of HE4 and CA125 may be recommended as potential biomarkers in the preliminary differential diagnosis of PTB from EOC before the "golden standard" of pathologic diagnosis finally obtained. PMID- 26667153 TI - ABA-HYPERSENSITIVE BTB/POZ PROTEIN 1 functions as a negative regulator in ABA mediated inhibition of germination in Arabidopsis. AB - To elucidate the contribution of CRL3-ABA-mediated responses, we attempted to find CRL3 substrate receptors involved in ABA signaling. One gene named ABA HYPERSENSITIVE BTB/POZ PROTEIN 1 (AHT1) was upregulated more than 2.5 times by ABA, and its coding region possessed a BTB/POZ domain, which is the common feature of CRL3 substrate receptors. Loss of AHT1 led to retardation of the germination process, not inhibition of root growth. AHT1 transcripts also increased in response to mannitol, NaCl and drought treatments at the seedling stage and in dry seeds. High expression of AHT1 in dry seeds was inhibited by the defect of ABA signaling components such as ABI1, ABI3 and SRKs indicating that the expression of AHT1 is dependent on ABA signaling. Among bZIP transcription factors participating in ABA signaling, the losses of ABI5/DPBF1, AREB1/ABF2, EEL/DPBF4 and DPBF2/bZIP67 resulted in reduced AHT1 expression, showing that these transcription factors play a positive role in ABA-induced AHT1 expression. While loss of AHT1 did not affect the expression pattern of NCED3, ABI2, SRKs and AREB/ABF genes, it led to hyperinduction of ABI5/DPBF genes such as ABI5/DPBF1, EEL/DPBF4 and AREB3/DPBF3, which are mainly involved in seed development and germination, as well as ABA-inducible genes transactivated by ABI5. Overall, these findings indicate that AHT1 negatively regulates ABA-mediated inhibition of germination, possibly by repressing the expression of a subset of ABI5/DPBF subfamily genes, and that AHT1 may be regulated by a negative feedback process through its linkage with a part of ABI5/DPBF proteins. PMID- 26667155 TI - Breaking of the site-bond percolation universality in networks. AB - The stochastic addition of either vertices or connections in a network leads to the observation of the percolation transition, a structural change with the appearance of a connected component encompassing a finite fraction of the system. Percolation has always been regarded as a substrate-dependent but model independent process, in the sense that the critical exponents of the transition are determined by the geometry of the system, but they are identical for the bond and site percolation models. Here, we report a violation of such assumption. We provide analytical and numerical evidence of a difference in the values of the critical exponents between the bond and site percolation models in networks with null percolation thresholds, such as scale-free graphs with diverging second moment of the degree distribution. We discuss possible implications of our results in real networks, and provide additional insights on the anomalous nature of the percolation transition with null threshold. PMID- 26667156 TI - Prospective study of vocal fold function after loss of the neuromonitoring signal in thyroid surgery: The International Neural Monitoring Study Group's POLT study. AB - OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring identifies recurrent laryngeal nerve (RLN) injury and gives prognostic information regarding postoperative glottic function. Loss of the neuromonitoring signal (LOS) signifies segmental type 1 or global type 2 RLN injury. This study aimed at identifying risk factors for RLN injury and determining vocal fold (VF) function initially and 6 months after definitive LOS. STUDY DESIGN: Prospective study encompassing 21 hospitals from 13 countries. METHODS: Included in this study were patients with persistent intraoperative LOS. RESULTS: At first postoperative laryngoscopy, early VF palsy was present in 94 of all 115 patients with LOS (81.7%): in 53 of 56 patients (94.6%) with type 1 injury and 41 of 59 patients (69.5%) with type 2 injury. In LOS type 1, women outnumbered men >5-fold. Traction produced LOS type 1 in 38 of 56 patients (67.9%) and LOS type 2 in 54 of 59 patients (91.5%). Course of the RLN posterior and/or anterior to the inferior thyroid artery, extralaryngeal branching, or tuberculum of Zuckerkandl did not increase VF palsy rates. Permanent VF palsy rates were also lower (P = .661) after LOS type 2 than after LOS type 1: 6.8% (four of 59 patients) versus 10.7% (six of 56 patients). Intraoperative administration of steroids did not diminish postoperative VF palsy rates. CONCLUSIONS: LOS type 1 entails more severe nerve damage than LOS type 2, affecting women disproportionately. Both LOS types, being primarily associated with traction injury, are unaffected by variant neck anatomy in expert hands and unresponsive to steroids. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1260-1266, 2016. PMID- 26667157 TI - Potential Roles of Humanin on Apoptosis in the Heart. AB - The process of programmed cell death, or apoptosis, is known as a key player in the development and progression of cardiovascular disease. The proposed mechanism for apoptosis is the activation of two main apoptotic signaling pathways (the extrinsic and intrinsic pathways), which lead to cell death. As the rate and amount of cardiomyocyte loss is the most important determinant of patient morbidity and mortality, novel treatment strategies targeting apoptosis are crucial. Recently, Humanin has been shown to exert protective effects against cellular apoptosis in both experimental and clinical studies. The potential cardioprotective mechanisms of Humanin have been shown to involve both the extracellular and intracellular signaling pathways. In this review, the current knowledge and the mechanisms inhibiting cellular apoptosis by Humanin during cardiac injury are comprehensively summarized. In addition, both research and clinical findings regarding the effects of Humanin on the heart and vasculature are also presented and discussed. Currently available information suggests that Humanin may exert cardioprotective benefits and could potentially be used as a novel pharmacological intervention against cellular apoptosis during myocardial injury. PMID- 26667158 TI - Strain, Psychological Conflicts, Aspirations-Attainment Gap, and Depressive Tendencies among Youth of Mexican Immigrants. AB - Using Children of Immigrants Longitudinal Study (CILS), this study examined the links between strain, psychological conflicts, aspiration-attainment gap, and depressive tendencies of 755 youth of Mexican origin. Two research questions were raised: (a) What types of strain and psychological conflict induced depressive tendencies? (b) What types of aspirations were relevant to these depressive symptoms? Overall, this study showed that factors implicated by collision of values, perceived discrepancies between aspiration and attainment, and negative appraisal of self could induce depressive mood, feelings, and behaviors, an important finding revealing that this underserved population can benefit from better public health services. PMID- 26667159 TI - A simple coculture system shows mutualism between anaerobic faecalibacteria and epithelial Caco-2 cells. AB - Most gut bacteria are obligate anaerobes and are important for human health. However, little mechanistic insight is available on the health benefits of specific anaerobic gut bacteria. A main obstacle in generating such knowledge is the lack of simple and robust coculturing methods for anaerobic bacteria and oxygen-requiring human cells. Here, we describe the development of a coculture system for intestinal Caco-2 cells and an anaerobic symbiont, Faecalibacterium prausnitzii, making use of 50 mL culture tubes. F. prausnitzii was grown in 40 mL YCFAG-agar with glass-adhered Caco-2 cells placed on top in 10 mL DMEM medium. Grown for 18-36 h in a humidified incubator at 37 degrees C and 5% CO2, coverslip-attached Caco-2 cells promoted growth and metabolism of F. prausnitzii, while F. prausnitzii suppressed inflammation and oxidative stress in Caco-2 cells. F. prausnitzii did not compromise Caco-2 cell viability. Exogenously added porcine mucin also promoted growth of F. prausnitzii, suggesting that it may be part of the mechanism of Caco-2-stimulated growth of F. prausnitzii. This 'Human oxygen-Bacteria anaerobic' (HoxBan) coculturing system uniquely establishes host microbe mutualism of a beneficial anaerobic gut microbe in vitro and principally allows the analysis of host-microbe interactions of pure and mixed cultures of bacteria and human cells. PMID- 26667160 TI - The addicted brain: cognitive biases in problematic drinkers with mild to borderline intellectual disability. AB - BACKGROUND: Substance use disorders (SUD) are associated with several neurobiological disruptions, including biases in attention and approach/avoidance behaviour. The aims of this study were to compare the strength of cognitive biases between light and problematic drinkers, to explore the role of IQ on the cognitive biases and to study the psychometric qualities of the measures. METHOD: Participants (N = 130) were divided into four groups based on IQ and severity of alcohol use-related problems: light (n = 28) and problematic drinkers (n = 25) with (sub)average IQ and light (n = 33) and problematic drinkers (n = 44) with mild to borderline intellectual disability (MBID). All participants performed the visual dot probe task and the approach avoidance task to measure the strength of cognitive biases. RESULTS: In contrast with the hypothesis, no cognitive biases were found in problematic drinkers. Full scale IQ nor level of craving influenced the strength of the cognitive biases in light and problematic drinkers, although IQ did influence task performance (i.e. large intra-individual, trial-to-trial variation in reaction time). The internal consistency of the visual dot probe task was good, whereas the internal consistency of the approach avoidance task was poor. CONCLUSION: Cognitive biases seem to vary within the group of problematic drinkers as a whole. The psychometric qualities of the measures are problematic, especially in relation to the intra-individual variability in reaction time found in participants with MBID. Until the implications of this variability on the validity of implicit measures and establishing bias scores are more clear, the use of these measures in individuals with MBID calls for scrutiny. PMID- 26667161 TI - Gastric Bypass Surgery but not Caloric Restriction Improves Reproductive Function in Obese Mice. AB - In women, obesity is associated with decrements in reproductive health that are improved with weight loss. Due to the difficulty of maintaining weight loss through lifestyle interventions, surgical interventions have become popular treatments for obesity. We examined how weight loss induced by Roux-en Y gastric bypass surgery (RYGB) or calorie restriction impacted expression of hypothalamic genes related to energy intake and reproduction. RYGB and calorie restriction induced equivalent weight loss; however, expression of the anorexigenic melanocortin pathway decreased only in calorie restricted mice. Serum estradiol concentrations were lower in calorie restricted mice relative to RYGB during proestrous, suggesting that RYGB maintained normal estrous cycling. Thus, the effects of RYGB for female mice, and possibly humans, extend beyond weight loss to include enhanced reproductive health. PMID- 26667162 TI - Validation of Obesity Surgery Data in the Swedish National Patient Registry and Scandinavian Obesity Registry (SOReg). AB - BACKGROUND AND AIM: Swedish health registries are common sources of data for studies on the effects of obesity surgery, and there is a need to assess the quality of data in these registries. The aim of this study was to validate the registration of obesity surgery in the National Patient Registry (NPR) and the Scandinavian Obesity Surgery Registry (SOReg). METHOD: We randomly selected 962 out of 8501 registrations of obesity surgery in 2011 from the NPR and SOReg. Registered surgical procedures in the NPR and SOReg were compared to the medical records, and concordance was analyzed by calculating positive predictive value (PPV) with 95 % confidence interval (CI). RESULTS: We received 938 (98 %) medical records for manual review. The overall PPV for obesity surgery was high in the NPR (PPV 97.0; 95 % CI 95.6-98.4) and even higher in SOReg (PPV 99.7; 95 % CI 99.3-100). Accuracy was higher for gastric bypass surgery than for other types of obesity surgery. Registrations that were misclassified as obesity surgery (n = 44) included reoperations due to complications or reconstruction to normal anatomy after previous obesity surgery (n = 11) and endoscopic procedures (n = 10). CONCLUSION: Obesity surgery registrations in the NPR and SOReg have high accuracy and are reliable sources of data to identify patients having undergone obesity surgery. When it is of importance to distinguish between specific surgical procedures, non-gastric bypass surgeries in the NPR should ideally be supplemented with data from other sources. PMID- 26667163 TI - Lower Esophageal Magnetic Sphincter Augmentation for Persistent Reflux After Roux en-Y Gastric Bypass. AB - Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a good option for the treatment of gastroesophageal reflux disease (GERD) in the obese population. However, some patients have significant reflux despite this procedure, and their treatment might be challenging. Laparoscopic lower esophageal magnetic sphincter augmentation (MSA) has been introduced into clinical practice with encouraging results. Currently, MSA is only approved for patients with hiatal hernias that are less than 3 cm and without history of antireflux procedures. We present two cases of MSA for the treatment of persistent GERD after LRYGB. Since this is an off-label use of this procedure, both patients underwent extensive evaluation before proceeding with surgery. Excellent results were obtained with a significant improvement in symptoms as well as their GERD Health-Related Quality of Life scores. PMID- 26667164 TI - Roux-en-Y Gastric Bypass in the Elderly: a Systematic Review. AB - The prevalence of severe obesity in the elderly is increasing. This systematic review reviews the literature in reference to the efficacy and safety of bariatric surgery on the elderly patient >= 65 years. A comprehensive search of electronic databases was completed. The data was limited to include only Roux-en Y gastric bypass patients >= 65 years. Eight primary studies (1835 patients) were included, all case series. Mean age was 67.6 years. Mean excess weight loss at study endpoint was 66.2 %. Mean 30-day mortality was 0.14 %. The mean total post operative complication rate was 21.1 %, with wound infections being the most common (7.58 %) followed by cardiorespiratory complications (2.96 %). Bariatric surgery is effective in producing marked weight loss in patients >= 65 years with an acceptable safety profile. PMID- 26667165 TI - Is Gastric Banding Appropriate in Indigenous Or Remote-Dwelling Persons? AB - BACKGROUND: Gastric banding has been promoted as less suitable for indigenous persons or persons who live remotely as it requires in person follow-up for band adjustment and may have higher rates of reoperation. This study assessed being an indigenous Australian or living remotely (but not both) on outcomes following gastric banding. METHODS: Data was prospectively recorded on all 559 patients who underwent gastric banding by one surgeon at one private hospital in Darwin, between February 1998 and August 2014. RESULTS: Forty persons (7 %) were indigenous and 93 (17 %) were remotely living (only 7 were both). At the last assessment (follow-up 37 (SD 31) months), overall percentage of excess weight loss (EWL) was 53 % (30 %), the percentage of total weight loss (TWL) was 23 (13), and 389 (70 %) achieved >50 % EWL. Seventy-two percent (43/60) ceased all diabetic medications. Ninety-two (17 %) came to reoperation. There was little difference between the indigenous and non-indigenous metropolitan-living groups, or between the remote and metropolitan non-indigenous groups in %EWL, %TWL, the proportion who achieved more than 50 % EWL, the time to achieve the goal weight, or cessation of diabetes medication. Similarly, there was little difference in the time to band removal or replacement. No person was directly compromised at band removal/replacement by delay due to dwelling remotely. CONCLUSIONS: In these select persons who underwent gastric banding in the private sector only, outcomes of weight loss and revisional surgery were acceptable and comparable between indigenous and non-indigenous metropolitan-dwelling persons as well as between remote and metropolitan-dwelling non-indigenous persons. PMID- 26667166 TI - Letter to the Editor. PMID- 26667167 TI - The Costimulatory Molecule ICOS Regulates Host Th1 and Follicular Th Cell Differentiation in Response to Plasmodium chabaudi chabaudi AS Infection. AB - Blood-stage Plasmodium chabaudi chabaudi AS infection requires cell- and Ab mediated immunity to control acute and persistent infection, respectively. ICOS regulates CD4(+) T cell activation and promotes the induction of follicular Th (TFH) cells, CD4(+) T cells that support B cell affinity maturation within germinal centers (GCs), resulting in the production of high-affinity Abs. In this article, we demonstrate that, in response to P. c. chabaudi AS infection, the absence of ICOS resulted in an enhanced Th1 immune response that reduced peak parasitemia. Despite the absence of ICOS, CD4(+) T cells were capable of expressing PD-1, B cell lymphoma 6, and CXCR5 during early infection, indicating TFH development was not impaired. However, by day 21 postinfection, Icos(-/-) mice accumulated fewer splenic TFHs compared with Icos(+/+) mice, leading to substantially fewer GC B cells and a decrease in affinity, but not production, of parasite-specific isotype-switched Abs. Moreover, treatment of mice with anti ICOS ligand Abs to modulate ICOS-ICOS ligand signaling revealed a requirement for ICOS in TFH differentiation only after day 6 postinfection. Ultimately, the quality and quantity of isotype-switched Abs produced in Icos(-/-) mice declined over time, resulting in impaired control of persistent parasitemia. Collectively, these data suggest ICOS is not required for TFH induction during P. c. chabaudi AS infection or production of isotype-switched Abs, but it is necessary for maintenance of a sustained high-affinity, protective Ab response. PMID- 26667168 TI - Protein Inhibitor of Activated STAT3 Regulates Migration, Invasion, and Activation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis. AB - The aggressive phenotype displayed by fibroblast-like synoviocytes (FLSs) is a critical factor of cartilage destruction in rheumatoid arthritis (RA). Increased FLSs migration and subsequent degradation of the extracellular matrix are essential to the pathology of RA. Protein inhibitor of activated STAT (PIAS), whose family members include PIAS1, PIAS2 (PIASx), PIAS3, and PIAS4 (PIASy), play important roles in regulating various cellular events, such as cell survival, migration, and signal transduction in many cell types. However, whether PIAS proteins have a role in the pathogenesis of RA is unclear. In this study, we evaluated the role of PIAS proteins in FLSs migration, invasion, and matrix metalloproteinases (MMPs) expression in RA. We observed increased expression of PIAS3, but not PIAS1, PIAS2, or PIAS4, in FLSs and synovial tissues from patients with RA. We found that PIAS3 knockdown by short hairpin RNA reduced migration, invasion, and MMP-3, MMP-9, and MMP-13 expression in FLSs. In addition, we demonstrated that PIAS3 regulated lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of PIAS3 knockdown on Rac1/PAK1 and JNK activation. Our results indicated that PIAS3 mediated SUMOylation of Rac1 controlled its activation and modulated the Rac1 downstream activity of PAK1 and JNK. Furthermore, inhibition of Rac1, PAK1, or JNK decreased migration and invasion of RA FLSs. Thus, our observations suggest that PIAS3 suppression may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, and activation. PMID- 26667169 TI - SATB1 Plays a Critical Role in Establishment of Immune Tolerance. AB - Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4(+)CD8(+) double positive stage during T cell development in the thymus. We also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 cKO mice, the numbers of Foxp3(+) regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATB1 cKO mice were still less than those in wild-type littermates at adulthood. Suppressive functions of Treg cells, which play a major role in establishment of peripheral tolerance, were also affected in the absence of SATB1. In addition, negative selection during T cell development in the thymus was severely impaired in SATB1 deficient mice. These results suggest that SATB1 plays an essential role in establishment of immune tolerance. PMID- 26667171 TI - Categorical Analysis of Human T Cell Heterogeneity with One-Dimensional Soli Expression by Nonlinear Stochastic Embedding. AB - Rapid progress in single-cell analysis methods allow for exploration of cellular diversity at unprecedented depth and throughput. Visualizing and understanding these large, high-dimensional datasets poses a major analytical challenge. Mass cytometry allows for simultaneous measurement of >40 different proteins, permitting in-depth analysis of multiple aspects of cellular diversity. In this article, we present one-dimensional soli-expression by nonlinear stochastic embedding (One-SENSE), a dimensionality reduction method based on the t distributed stochastic neighbor embedding (t-SNE) algorithm, for categorical analysis of mass cytometry data. With One-SENSE, measured parameters are grouped into predefined categories, and cells are projected onto a space composed of one dimension for each category. In contrast with higher-dimensional t-SNE, each dimension (plot axis) in One-SENSE has biological meaning that can be easily annotated with binned heat plots. We applied One-SENSE to probe relationships between categories of human T cell phenotypes and observed previously unappreciated cellular populations within an orchestrated view of immune cell diversity. The presentation of high-dimensional cytometric data using One-SENSE showed a significant improvement in distinguished T cell diversity compared with the original t-SNE algorithm and could be useful for any high-dimensional dataset. PMID- 26667170 TI - Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces CD4+ T Cell Anergy via GRAIL. AB - Mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit CD4(+) T cell activation by downregulating the phosphorylation of key proximal TCR signaling molecules: Lck, CD3zeta, ZAP70, and LAT. Inhibition of proximal TCR signaling can result in T cell anergy, in which T cells are inactivated following an Ag encounter, yet remain viable and hyporesponsive. We tested whether mannose capped lipoarabinomannan (LAM)-induced inhibition of CD4(+) T cell activation resulted in CD4(+) T cell anergy. The presence of LAM during primary stimulation of P25 TCR-transgenic murine CD4(+) T cells with M. tuberculosis Ag85B peptide resulted in decreased proliferation and IL-2 production. P25 TCR-transgenic CD4(+) T cells primed in the presence of LAM also exhibited decreased response upon restimulation with Ag85B. The T cell anergic state persisted after the removal of LAM. Hyporesponsiveness to restimulation was not due to apoptosis, generation of Foxp3-positive regulatory T cells, or inhibitory cytokines. Acquisition of the anergic phenotype correlated with upregulation of gene related to anergy in lymphocytes (GRAIL) protein in CD4(+) T cells. Inhibition of human CD4(+) T cell activation by LAM also was associated with increased GRAIL expression. Small interfering RNA-mediated knockdown of GRAIL before LAM treatment abrogated LAM-induced hyporesponsiveness. In addition, exogenous IL-2 reversed defective proliferation by downregulating GRAIL expression. These results demonstrate that LAM upregulates GRAIL to induce anergy in Ag-reactive CD4(+) T cells. Induction of CD4(+) T cell anergy by LAM may represent one mechanism by which M. tuberculosis evades T cell recognition. PMID- 26667172 TI - Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection. AB - Many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. Intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS inducible protein in macrophages, affects both lysosomal biogenesis and activity. AGS3 binds the Gi family of G proteins via its G-protein regulatory (GoLoco) motif, stabilizing the Galpha subunit in its GDP-bound conformation. Elevated AGS3 levels in macrophages limited the activity of the mammalian target of rapamycin pathway, a sensor of cellular nutritional status. This triggered the nuclear translocation of transcription factor EB, a known activator of lysosomal gene transcription. In contrast, AGS3-deficient macrophages had increased mammalian target of rapamycin activity, reduced transcription factor EB activity, and a lower lysosomal mass. High levels of AGS3 in macrophages enhanced their resistance to infection by Burkholderia cenocepacia J2315, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus, whereas AGS3 deficient macrophages were more susceptible. We conclude that LPS priming increases AGS3 levels, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens. PMID- 26667173 TI - Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses. AB - Marginal zone (MZ) and B1 B cells have the capacity to respond to foreign Ags more rapidly than conventional B cells, providing early immune responses to blood borne pathogens. Ly9 (CD229, SLAMF3), a member of the signaling lymphocytic activation molecule family receptors, has been implicated in the development and function of innate T lymphocytes. In this article, we provide evidence that in Ly9-deficient mice splenic transitional 1, MZ, and B1a B cells are markedly expanded, whereas development of B lymphocytes in bone marrow is unaltered. Consistent with an increased number of these B cell subsets, we detected elevated levels of IgG3 natural Abs and a striking increase of T-independent type II Abs after immunization with 2,4,6-trinitrophenyl-Ficoll in the serum of Ly9-deficient mice. The notion that Ly9 could be a negative regulator of innate-like B cell responses was supported by the observation that administering an mAb directed against Ly9 to wild-type mice selectively eliminated splenic MZ B cells and significantly reduced the numbers of B1 and transitional 1 B cells. In addition, Ly9 mAb dramatically diminished in vivo humoral responses and caused a selective downregulation of the CD19/CD21/CD81 complex on B cells and concomitantly an impaired B cell survival and activation in an Fc-independent manner. We conclude that altered signaling caused by the absence of Ly9 or induced by anti-Ly9 may negatively regulate development and function of innate-like B cells by modulating B cell activation thresholds. The results suggest that Ly9 could serve as a novel target for the treatment of B cell-related diseases. PMID- 26667174 TI - Epithelioid/rhabdoid glioblastoma: a highly aggressive subtype of glioblastoma. AB - Epithelioid glioblastoma (GBM) and rhabdoid GBM are rare variants that are morphologically similar, but there is no consensus on the characteristics of each disease. These tumors have aggressive features of early recurrence and leptomeningeal dissemination and tend to develop in younger patients compared to typical GBM. The prognosis is normally worse than typical GBM, even with intensive chemoradiotherapy after surgical resection. Thus, accurate diagnosis and effective therapy for epithelioid/rhabdoid GBM are required. Four consecutive patients aged 16-48 years were diagnosed with epithelioid/rhabdoid GBM by pathological and immunohistochemical analysis at Yamaguchi University Hospital from 2006 to 2012. Two of these patients had relatively long-term survival (19 and 23 months after diagnosis). Two cases had a BRAF V600E mutation, whereas no ATRX mutation was present in any cases. All patients suffered leptomeningeal and/or spinal dissemination that worsened their prognosis. These results illustrate the need for a new therapeutic approach, such as molecular targeted drug therapy like BRAF inhibition, in addition to standard chemoradiotherapy for typical GBM. PMID- 26667176 TI - Rhetoric and reality - matching palliative care services to meet the needs of patients of all ages, with any diagnosis. PMID- 26667175 TI - Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone. AB - Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy. PMID- 26667177 TI - Microsatellite loci cross-species transferability in Aedes fluviatilis (Diptera:Culicidae): a cost-effective approach for population genetics studies. AB - BACKGROUND: Aedes fluviatilis is a neotropical mosquito species thought to be a potential vector of Yellow Fever viruses and can be infected with Plasmodium gallinaceum in laboratory. A better understanding of its genetic structure is very important to understand its epidemiologic potential and how it is responding to urbanization. The objective of this study was to survey the transferability of microsatellites loci developed for other Aedes to Ae. fluviatilis. FINDINGS: We tested in Ae. fluviatilis 40 pairs of primers known to flank microsatellite regions in Aedes aegypti, Aedes albopictus and Aedes caspius, and found eight loci that amplified consistently. The number of alleles per locus ranged from 2 to 15, and the expected heterozygosity ranged from 0.09 to 0.85. CONCLUSIONS: We found that several microsatellite primers successfully transferred to Ae. fluviatilis. This finding opens avenues for cost-effective optimization of high resolution population genetic tools. PMID- 26667178 TI - Ambient Molecular Analysis of Biological Tissue Using Low-Energy, Femtosecond Laser Vaporization and Nanospray Postionization Mass Spectrometry. AB - Direct analysis of plant and animal tissue samples by laser electrospray mass spectrometry (LEMS) was investigated using low-energy, femtosecond duration laser vaporization at wavelengths of 800 and 1042 nm followed by nanospray postionization. Low-energy (<50 MUJ), fiber-based 1042 nm LEMS (F-LEMS) allowed interrogation of the molecular species in fresh flower petal and leaf samples using 435 fs, 10 Hz bursts of 20 pulses from a Ytterbium-doped fiber laser and revealed comparable results to high energy (75-1120 MUJ), 45 fs, 800 nm Ti:Sapphire-based LEMS (Ti:Sapphire-LEMS) measurements. Anthocyanins, sugars, and other metabolites were successfully detected and revealed the anticipated metabolite profile for the petal and leaf samples. Phospholipids, especially phosphatidylcholine, were identified from a fresh mouse brain section sample using Ti:Sapphire-LEMS without the application of matrix. These lipid features were suppressed in both the fiber-based and Ti:Sapphire-based LEMS measurements when the brain sample was prepared using the optimal cutting temperature compounds that are commonly used in animal tissue cryosections. PMID- 26667179 TI - Influence of Sulfolane on ESI-MS Measurements of Protein-Ligand Affinities. AB - The results of an investigation into the influence of sulfolane, a commonly used supercharging agent, on electrospray ionization mass spectrometry (ESI-MS) measurements of protein-ligand affinities are described. Binding measurements carried out on four protein-carbohydrate complexes, lysozyme with beta-D-GlcNAc (1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc-(1->4)-D-GlcNAc, a single chain variable fragment and alpha-D-Gal-(1->2)-[alpha-D-Abe-(1->3)]-alpha-D-Man-OCH3, cholera toxin B subunit homopentamer with beta-D-Gal-(1->3)-beta-D-GalNAc-(1 >4)[alpha-D-Neu5Ac-(2->3)]-beta-D-Gal-(1->4)-beta-D-Glc, and a fragment of galectin 3 and alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-beta-D-GlcNAc-(1->3)-beta-D Gal-(1->4)-beta-D-Glc, revealed that sulfolane generally reduces the apparent (as measured by ESI-MS) protein-ligand affinities. To establish the origin of this effect, a detailed study was undertaken using the lysozyme-tetrasaccharide interaction as a model system. Measurements carried out using isothermal titration calorimetry (ITC), circular dichroism, and nuclear magnetic resonance spectroscopies reveal that sulfolane reduces the binding affinity in solution but does not cause any significant change in the higher order structure of lysozyme or to the intermolecular interactions. These observations confirm that changes to the structure of lysozyme in bulk solution are not responsible for the supercharging effect induced by sulfolane. Moreover, the agreement between the ESI-MS and ITC-derived affinities indicates that there is no dissociation of the complex during ESI or in the gas phase (i.e., in-source dissociation). This finding suggests that supercharging of lysozyme by sulfolane is not related to protein unfolding during the ESI process. Binding measurements performed using liquid sample desorption ESI-MS revealed that protein supercharging with sulfolane can be achieved without a reduction in affinity. PMID- 26667180 TI - Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm. AB - Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-gamma, TNF-alpha, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-gamma and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1beta and TNF alpha expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop. PMID- 26667182 TI - Heteroaggregation assisted wet synthesis of core-shell silver-silica-cadmium selenide nanowires. AB - A method has been developed for the wet solution synthesis of core shell heterogeneous nanowires. An ultrathin silica layer was first grown around plain silver nanowires to act as a suitable insulator. An outer nanoparticle layer was then attached through heteroaggregation by dispersing the un-functionalized nanowires in toluene solutions containing nanoparticles of CdSe or Au. Total coverage of nanoparticles on nanowires was found to increase with the nanoparticle size, which is attributed to the increase in the van der Waals interaction between the nanoparticles and the nanowire with the increasing size of nanoparticles. Using this method, we achieved over 79.5% coverage of CdSe nanoparticles (24 nm * 11 nm) on the nanowire surface. Although following the same trend, Au nanoparticles show an overall lower coverage than CdSe, with only 24.2% coverage at their largest particle size of 19 nm in diameter. This result is attributed to the increase in steric repulsion during attachment due to the increasing length of capping ligands. Investigation of the core-shell nanowire's optical properties yielded CdSe Raman peak enhancement by a factor of 2-3 due to the excitation of surface plasmon propagation. Our method can be applied to the attachment of a wide range of nanoparticles to nanowire materials in non-polar solution and the core-shell nanowires show great potential for incorporation into various microscopic and drug delivery applications. PMID- 26667181 TI - A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation. AB - A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both gamma-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by gamma irradiation, including HP1beta-, gammaH2AX- and Rad51-foci formation. DNMT3B RNAi impaired damage-dependent H2AX accumulation and showed a reduced level of gammaH2AX induction after gamma-irradiation. DNMT3B interacted with HP1beta in non-irradiated conditions, whereas irradiation abrogated the DNMT3B/HP1beta complex but induced interaction between DNMT3B and H2AX. Consistent with radiosensitization, TP63, BAX, PUMA and NOXA expression was induced after gamma irradiation in DNMT3B knockdown cells. Together with the observation that H2AX overexpression canceled radiosensitization by DNMT3B RNAi, these results suggest that DNMT3B RNAi induced radiosensitization through impairment of damage dependent HP1beta foci formation and efficient gammaH2AX-induction mechanisms including H2AX accumulation. Enhanced radiosensitivity by DNMT3B RNAi was also observed in a tumor xenograft model. Taken together, the current study implies that comprehensive screening accompanied by a cluster analysis enabled the identification of radiosensitization targets. Downregulation of DNMT3B, one of the targets identified using this method, radiosensitizes cancer cells by disturbing multiple DNA damage responses. PMID- 26667183 TI - The effects of tumour necrosis factor-alpha on bone cells involved in periodontal alveolar bone loss; osteoclasts, osteoblasts and osteocytes. AB - Periodontitis is the most common bone loss pathology in adults and if left untreated is responsible for premature tooth loss. Cytokines, such as tumour necrosis factor-alpha (TNFalpha), involved in the chronic inflammatory response within the periodontal gingiva, significantly influence the normal bone remodelling processes. In this review, the effects of TNFalpha on bone metabolism in periodontitis are evaluated in relation to its direct and indirect actions on bone cells including osteoclasts, osteoblasts and osteocytes. Evidence published to date suggests a potent catabolic role for TNFalpha through the stimulation of osteoclastic bone resorption as well as the suppression of osteoblastic bone formation and osteocytic survival. However, the extent and timing of TNFalpha exposure in vitro and in vivo greatly influences its effect on skeletal cells, with contradictory anabolic activity observed with TNFalpha in a number of studies. None the less, it is evident that managing the chronic inflammatory response in addition to the deregulated bone metabolism is required to improve periodontal and inflammatory bone loss treatments???????????????????????????????????????. PMID- 26667184 TI - There is no Melba but Melba. PMID- 26667185 TI - Rapid loss of antipredatory behaviour in captive-bred birds is linked to current avian invasions. AB - Despite the importance of behaviour in conservation biology, there have been few studies that address behaviour in areas such as invasion ecology. There is an urgent need to identify specific traits that facilitate the establishment and spread of alien species to prevent biological invasions and their impact on biodiversity. Changes in antipredatory behaviour in captivity have been proposed to explain the higher invasiveness of wild-caught exotic species. We experimentally tested this hypothesis by assessing the response of wild-caught and captive-bred cage birds facing an approaching predator and their ability to escape from human capture, using species available in the Spanish pet market. Results showed the loss of antipredatory responses and escape abilities in captive-bred birds compared with wild-caught ones. An intraspecific comparison between wild-caught and the first generation of captive-bred birds pointed to a rapid behavioural loss in captivity (individual lifetime) rather than to differences among species (evolutionary exposure). In the context of current avian invasions, the proportion of individuals showing antipredatory responses within a species was positively related to the likelihood of the species being found escaped and breeding in the wild. These results offer a link between behaviour, fitness, and the invasion syndrome in birds. PMID- 26667187 TI - Genome Sequence Analysis of New Isolates of the Winona Strain of Plum pox virus and the First Definitive Evidence of Intrastrain Recombination Events. AB - Plum pox virus (PPV) is genetically diverse with nine different strains identified. Mutations, indel events, and interstrain recombination events are known to contribute to the genetic diversity of PPV. This is the first report of intrastrain recombination events that contribute to PPV's genetic diversity. Fourteen isolates of the PPV strain Winona (W) were analyzed including nine new strain W isolates sequenced completely in this study. Isolates of other strains of PPV with more than one isolate with the complete genome sequence available in GenBank were included also in this study for comparison and analysis. Five intrastrain recombination events were detected among the PPV W isolates, one among PPV C strain isolates, and one among PPV M strain isolates. Four (29%) of the PPV W isolates analyzed are recombinants; one of which (P2-1) is a mosaic, with three recombination events identified. A new interstrain recombinant event was identified between a strain M isolate and a strain Rec isolate, a known recombinant. In silico recombination studies and pairwise distance analyses of PPV strain D isolates indicate that a threshold of genetic diversity exists for the detectability of recombination events, in the range of approximately 0.78*10( 2) to 1.33*10(-2) mean pairwise distance. RDP4 analyses indicate that in the case of PPV Rec isolates there may be a recombinant breakpoint distinct from the obvious transition point of strain sequences. Evidence was obtained that indicates that the frequency of PPV recombination is underestimated, which may be true for other RNA viruses where low genetic diversity exists. PMID- 26667186 TI - Evolution of Compatibility Range in the Rice-Magnaporthe oryzae System: An Uneven Distribution of R Genes Between Rice Subspecies. AB - Efficient strategies for limiting the impact of pathogens on crops require a good understanding of the factors underlying the evolution of compatibility range for the pathogens and host plants, i.e., the set of host genotypes that a particular pathogen genotype can infect and the set of pathogen genotypes that can infect a particular host genotype. Until now, little is known about the evolutionary and ecological factors driving compatibility ranges in systems implicating crop plants. We studied the evolution of host and pathogen compatibility ranges for rice blast disease, which is caused by the ascomycete Magnaporthe oryzae. We challenged 61 rice varieties from three rice subspecies with 31 strains of M. oryzae collected worldwide from all major known genetic groups. We determined the compatibility range of each plant variety and pathogen genotype and the severity of each plant-pathogen interaction. Compatibility ranges differed between rice subspecies, with the most resistant subspecies selecting for pathogens with broader compatibility ranges and the least resistant subspecies selecting for pathogens with narrower compatibility ranges. These results are consistent with a nested distribution of R genes between rice subspecies. PMID- 26667188 TI - Pepino mosaic virus RNA-Dependent RNA Polymerase POL Domain Is a Hypersensitive Response-Like Elicitor Shared by Necrotic and Mild Isolates. AB - Pepino mosaic virus (PepMV) is an emerging pathogen that represents a serious threat to tomato production worldwide. PepMV-induced diseases manifest with a wide range of symptoms, including systemic necrosis. Our results showed that PepMV accumulation depends on the virus isolate, tomato cultivar, and environmental conditions, and associates with the development of necrosis. Substitution of lysine for glutamic acid at position 67 in the triple gene block 3 (TGB3) protein, previously described as a necrosis determinant, led to increased virus accumulation and was necessary but not sufficient to induce systemic necrosis. Systemic necrosis both in tomato and Nicotiana benthamiana shared hypersensitive response (HR) features, allowing the assessment of the role of different genomic regions on necrosis induction. Overexpression of both TGB3 and the polymerase domain (POL) of the RNA-dependent RNA polymerase (RdRp) resulted in necrosis, although only local expression of POL triggered HR-like symptoms. Our results also indicated that the necrosis-eliciting activity of POL resides in its highly conserved "palm" domain, and that necrosis was jasmonic acid-dependent but not salicylic acid-dependent. Altogether, our data suggest that the RdRp-POL domain plays an important role in PepMV necrosis induction, with necrosis development depending on the virus accumulation level, which can be modulated by the nature of TGB3, host genotype and environmental conditions. PMID- 26667189 TI - Grass Hosts Harbor More Diverse Isolates of Puccinia striiformis Than Cereal Crops. AB - Puccinia striiformis causes stripe rust on cereal crops and many grass species. However, it is not clear whether the stripe rust populations on grasses are able to infect cereal crops and how closely they are related to each other. In this study, 103 isolates collected from wheat, barley, triticale, rye, and grasses in the United States were characterized by virulence tests and simple sequence repeat (SSR) markers. Of 69 pathotypes identified, 41 were virulent on some differentials of wheat only, 10 were virulent on some differentials of barley only, and 18 were virulent on some differentials of both wheat and barley. These pathotypes were clustered into three groups: group one containing isolates from wheat, triticale, rye, and grasses; group two isolates were from barley and grasses; and group three isolates were from grasses and wheat. SSR markers identified 44 multilocus genotypes (MLGs) and clustered them into three major molecular groups (MG) with MLGs in MG3 further classified into three subgroups. Isolates from cereal crops were present in one or more of the major or subgroups, but not all, whereas grass isolates were present in all of the major and subgroups. The results indicate that grasses harbor more diverse isolates of P. striiformis than the cereals. PMID- 26667190 TI - Dendritic Elastin-like Peptides: The Effect of Branching on Thermoresponsiveness. AB - Elastin-like peptides (ELPs) have been used widely to confer thermoresponsive characteristics onto various materials, but to this point mostly linear ELPs have been studied. A class of linear and dendritic (branched) ELPs based on the GLPGL pentamer repeat unit was synthesized using an on-resin divergent strategy. The effect of peptide topology on the transition temperature (Tt) was examined using circular dichroism to study the peptide secondary structure transition and turbidity to measure the macroscopic phase transition (coacervation). Secondary structure transitions showed no dependence on topology, but a higher Tt was observed for dendritic peptides than for linear peptides with the same number of GLPGL repeats. The data support a phase transition model that consists of two neighboring processes: a secondary structure transition, related to intramolecular interactions, followed by coacervation, associated with intermolecular interactions. PMID- 26667191 TI - Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. AB - BACKGROUND AND AIM: The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography. METHODS: Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta analysis. RESULTS: Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5 years (range: 3-14.7 years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80-2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43-1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71-2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76-1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5 years (range: 3-11 years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72-1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89-2.07) for GGT, and 3.22 (95% CI, 3.05-3.41) for ultrasonography, respectively. CONCLUSIONS: Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up. PMID- 26667192 TI - Chronic Psychological Stress as a Risk Factor of Osteoporosis. AB - Osteoporosis, the most common metabolic skeletal disease, is characterized by decreased bone mass and deteriorated bone quality, leading to increased fracture risk. With the aging of the population, osteoporotic fracture is an important public health issue. Organisms are constantly exposed to various stressful stimuli that affect physiological processes. Recent studies showed that chronic psychological stress is a risk factor for osteoporosis by various signaling pathways. The purpose of this article is to review the recent progress of the association between chronic psychological stress and osteoporosis. Increasing evidence confirms the physiological importance of the central nervous system, especially the hypothalamus, in the regulation of bone metabolism. Both animal and human studies indicate that chronic psychological stress induces a decrease of bone mass and deterioration of bone quality by influencing the hypothalamic pituitary-adrenocortical (HPA) axis, sympathetic nervous system, and other endocrine, immune factors. Active mastication, proven to be an effective stress coping behavior, can attenuate stress-induced neuroendocrine responses and ameliorate stress-induced bone loss. Therefore, active mastication may represent a useful approach in preventing and/or treating chronic stress-associated osteoporosis. We also discuss several potential mechanisms involved in the interaction between chronic stress, mastication and osteoporosis. Chronic stress activates the HPA axis and sympathetic nervous system, suppresses the secretion of gonadal hormone and growth hormone, and increases inflammatory cytokines, eventually leading to bone loss by inhibiting bone formation and stimulating bone resorption. PMID- 26667193 TI - Prenatal Exposure to 1-Bromopropane Suppresses Kainate-Induced Wet Dog Shakes in Immature Rats. AB - 1-Bromopropane (1-BP) is used in degreasing solvents and spray adhesives. The adverse effects of 1-BP have been reported in human cases and adult animal models, and its developmental toxicity has also been reported, but its effects on developmental neurotoxicity have not been investigated in detail. We evaluated the effects in rat pups of prenatal exposure to 1-BP on behaviors such as scratching and wet dog shakes (WDS), which were induced by injection of kainate (KA). Pregnant Wistar rats were exposed to vaporized 1-BP with 700 ppm from gestation day 1 to day 20 (6 h/day). KA at doses of 0.1, 0.5, and 2.0 mg/kg were intraperitoneally injected into a control group and a 1-BP-exposed group of pups on postnatal day 14. There was no significant difference in scratching between the control and the prenatally 1-BP-exposed groups, while suppression of the occurrence ratio of WDS was observed at the low dose of 0.1 mg/kg of KA in the prenatally 1-BP-exposed pups. Our results suggest that prenatal exposure to 1-BP affects neurobehavioral responses in the juvenile period. PMID- 26667194 TI - [Development of a Crisis Management Manual for Occupational Health Experts]. AB - When crises such as natural disasters or industrial accidents occur in workplaces, not only the workers who are injured, but also those who engage in emergency or recovery work may be exposed to various health hazards. We developed a manual to enable occupational health (OH) experts to prevent health hazards. The manual includes detailed explanations of the characteristics and necessary actions for each need in the list of "OH Needs During Crisis Management" developed after an analysis of eight cases in our previous research. We changed the endings of explanatory sentences so that users could learn how often each need occurred in these eight cases. We evaluated the validity of the manual using two processes: 1) Providing the manual to OH physicians during an industrial accident; 2) Asking crisis management experts to review the manual. We made improvements based on their feedback and completed the manual. The manual includes explanations about 99 OH needs, and users can learn how and what to do for each need during various crisis cases. Because additional OH needs may occur in other crises, it is necessary to collect information about new cases and to improve the comprehensiveness of the manual continuously. It is critical that this crisis management manual be available when a crisis occurs. We need to inform potential users of the manual through various media, as well as by posting it on our website. PMID- 26667195 TI - [Medical Humanities--the Historical Significance and Mission in Medical Education]. AB - In this paper we consider the significance and mission of medical humanities in medical education from the following six viewpoints: (1) misunderstanding of the medical humanities; (2) its historical development; (3) the criteria for the ideal physician; (4) the contents of current Medical Humanities education; (5) the basic philosophy; and (6) its relation to medical professionalism. Medical humanities consists of the three academic components of bioethics, clinical ethics and medical anthropology, and it is a philosophy and an art which penetrate to the fundamental essence of medicine. The purpose of medical humanities is to develop one's own humanity and spirituality through medical practice and contemplation by empathizing with patients' illness narratives through spiritual self-awakening and by understanding the mutual healing powers of human relations by way of the realization of primordial life. The basic philosophy is "the coincidence of contraries". The ultimate mission of medical humanities is to cultivate physicians to educate themselves and have a life-long philosophy of devotion to understanding, through experience, the coincidence of contraries. PMID- 26667196 TI - [Three Cases of Bacteremia due to Helicobacter cinaedi Infection and the Usefulness of Gene Analysis of Isolated Bacteria]. AB - Helicobacter cinaedi is typically isolated from immunocompromised patients. Some reports of infection caused by H.cinaedi have been found in recent years. We experienced three cases of H.cinaedi bacteremia in one year and ten months in our hospital, although the detection of H.cinaedi in blood cultures is extremely rare. In case 1, a 77-year-old female had been treated with a steroid and immunosuppressive agent for interstitial pneumonia. In cases 2 and 3, two 71-year old men had been treated with chemotherapy for lung cancer. Although the identification of the bacteria could not be performed by the culture method in the three cases, H.cinaedi bacteremia was diagnosed by a 16S rRNA gene sequencing analysis in case 1, and by nested PCR in cases 2 and 3. H.cinaedi bacteremia often tends to recur and also requires prolonged antimicrobial therapy. We believe that gene analysis is useful in the identification of H.cinaedi. PMID- 26667197 TI - [Effect of Intravitreal Bevacizumab Injection on Iris and Iridocorneal Angle Neovascularization in Neovascular Glaucoma]. AB - Neovascular glaucoma is a serious complication associated with retinal ischemic changes, which increase the production of vascular endothelial growth factor. Vascular endothelial growth factor has been implicated as a key molecule in the development of newly formed vessels and neovascular glaucoma. Intravitreal injection of bevacizumab, a full-length humanized anti-vascular endothelial growth factor monoclonal antibody, leads to a dramatic regression of the new iris and iridocorneal angle vessels on slitlamp examination. However, anterior segment angiography reveals that bevacizumab does not cause a regression of the neovascular vessels themselves but reduces vascular permeability while newly formed vessels are still present in the iris and iridocorneal angle. This review focuses on the pathology and diagnosis of neovascula glaucoma and the effect of intravitreal bevacizumab on the iris and iridocorneal angle neovascularization. PMID- 26667198 TI - [Implementation of Objective Structured Clinical Examination I of the Department of Nursing--Introduction of Simulation-Based Education]. AB - The Department of Nursing of the university revised its curriculum for students admitted in 2012 or later, including the introduction of integrated subjects. With the aim of improving the practical clinical skills of students and integrating knowledge, skills, and techniques, the following integrated subjects: Objective Structured Clinical Examination (OSCE) I held in the first term of the third-year (15 hours as one credit), and OSCE II held in the second term of the fourth year (30 hours as one credit), were adopted, and simulation-based education was introduced. In this report, we summarized our experience of a simulation education system for nursing students in the year 2014 aiming to improve students' skill of wheelchair transfer of a patient with left hemiplegia and patient's living environment. Many positive responses, such as usefulness in future nursing training, were obtained upon the introduction of the simulation education system. Issues to be addressed in the future, including lack of sufficient time to practice and availability of rooms, were also noticed. PMID- 26667199 TI - [Examination of the Prevention of Severe Hand Trauma Injury Cases due to Occupational Accidents--An Expert Opinion Gathering Meeting]. AB - We gathered seven specialists from various fields who are interested in worker injury prevention programs, based on cases of patients who had suffered refractory injuries requiring hand surgery because of industrial accidents. The patients were asked to write their thoughts and ideas on the theme, "Measures that must be implemented to prevent arm injuries." The content obtained was classified into different categories, using the KJ method, and was scripted to sort out the items. As a result, the following eleven points were identified as measures to prevent serious hand surgery-related injuries: 1. Purchase safe machinery, 2. Create a list of machines that require caution, 3. Enclose a machine's various rotating parts, 4. Carry out periodic maintenance work on the machines, 5. Indicate dangerous areas by putting up signs that attract attention, 6. Illuminate the rotating parts more brightly and avoid placing objects around them, 7. Systematically carry out safety education that creates a strong impact, 8. Encourage workers to look after their own health, 9. Announce policies on health and safety, 10. Re-examine the operational procedures, and 11. Be prepared in case an accident occurs. A perspective based on the results of this research is deemed important in creating a workplace improvement manual in the future. PMID- 26667202 TI - Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination. AB - DNA vaccines have advantages over traditional vaccine modalities; however the relatively low immunogenicity restrains its translation into clinical use. Further optimizations are needed to get the immunogenicity of DNA vaccine closer to the level required for human use. Here we show that intramuscularly inoculating into a different limb each time significantly improves the immunogenicities of both DNA and recombinant vaccinia vaccines during multiple vaccinations, compared to repeated vaccination on the same limb. We term this strategy successive site translocating inoculation (SSTI). SSTI could work in synergy with genetic adjuvant and DNA prime-recombinant vaccinia boost regimen. By comparing in vivo antigen expression, we found that SSTI avoided the specific inhibition of in vivo antigen expression, which was observed in the limbs being repeatedly inoculated. Employing in vivo T cell depletion and passive IgG transfer, we delineated that the inhibition was not mediated by CD8(+) T cells but by specific antibodies. Finally, by using C3(-/-) mouse model and in vivo NK cells depletion, we identified that specific antibodies negatively regulated the in vivo antigen expression primarily in a complement depended way. PMID- 26667203 TI - Latissimus dorsi intercostal artery perforator musculocutaneous flap in chest wall reconstruction. PMID- 26667204 TI - Adhesive small bowel obstruction after laparotomy during infancy. AB - BACKGROUND: Intra-abdominal adhesions can cause adhesive small bowel obstruction, chronic abdominal pain and female infertility. Reports on long-term outcomes following laparotomy during infancy are scarce. The aims of this study were to investigate the incidence of and risk factors for long-term adhesive small bowel obstruction and associated morbidity after laparotomy during infancy. METHODS: Infants who underwent laparotomy between 1976 and 2011 were identified. Data were extracted from medical records and a questionnaire was sent to the patients. RESULTS: Some 898 of 1185 eligible patients were included, with a median follow up time of 14.7 (range 0.0-36.0) years. Median age at first laparotomy was 6 (range 1.0-365.0) days. There were 113 patients (12.6 per cent) with adhesive small bowel obstruction who underwent relaparotomy, 79 (69.9 per cent) occurring during the first 2 years after the initial laparotomy. The highest incidence of small bowel obstruction was found in patients with Hirschsprung's disease (19 of 65, 29 per cent), malrotation (13 of 45, 29 per cent), intestinal atresia (11 of 40, 28 per cent) and necrotizing enterocolitis (16 of 64, 25 per cent). Lengthy duration of surgery (hazard ratio (HR) 1.25, 95 per cent c.i. 1.07 to 1.45), stoma formation (HR 1.72, 1.15 to 2.56) and postoperative complications (HR 1.81, 1.12 to 2.92) were independent risk factors. Chronic abdominal pain was reported in 180 (24.0 per cent) of 750 patients, and 17 (13.8 per cent) of 123 women reported infertility. CONCLUSION: The incidence of adhesive small bowel obstruction after laparotomy in infants is high. PMID- 26667205 TI - New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis. AB - WHAT IS KNOWN AND OBJECTIVE: Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. COMMENT: In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. WHAT IS NEW AND CONCLUSION: This 2 month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment. PMID- 26667206 TI - Rates of glaucomatous visual field change before and after transscleral cyclophotocoagulation: a retrospective case series. AB - BACKGROUND: The primary goal of glaucoma treatment is to lower and control intraocular pressure (IOP) and thereby prevent functional deterioration. For glaucomas that are refractory to medical and incisional surgical therapies, transscleral diode cyclophotocoagulation (TCP) is a well-established procedure to effectively decrease IOP. This study investigated rates of visual field (VF) change in patients with glaucoma before and after TCP. METHODS: This retrospective case series investigated rates of VF changes in glaucoma patients before and after they underwent TCP. At least four VF examinations were required, two before and two after surgery. VF examinations were performed using standard automated perimetry and rates of change were calculated by linear regression analysis of mean deviation (MD) values measured over time. RESULTS: A total of 46 eyes of 43 patients were included and followed on average 3.6 years before and 2.1 years after TCP. 67 % of the eyes showed further progression of glaucoma following surgery. Mean preoperative MD change was -0.21 dB/year (SE = 0.08, 95 % CI [-0.06, -0.37]). Postoperatively the mean change was -0.26 dB/year (SE = 0.22 95 % CI [0.38, -0.48]) which results in a difference between pre- and postoperative MD rate of 0.05 dB/year (p = 0.824). The mean MD value was worse after surgery and dropped by 1.73 dB (SE = 0.58, 95 % CI [-0.59, -2.87], p = 0.003). Intraocular pressure (IOP) decreased from 23.2 mmHg (SD = 4.67) before TCP to 14.3 mmHg (SD = 3.17) after TCP (p < 0.001). For each 1 mmHg of IOP reduction after surgery, postoperative rate of VF loss decreased by 0.15 dB/year. CONCLUSION: Rates of glaucomatous visual field loss did not significantly change after TCP and the majority of the eyes showed further progression of glaucoma after surgery. Mean MD value was considerably lower after TCP. PMID- 26667207 TI - Photic stimulation during electroencephalography: Efficacy and safety in an unselected cohort of patients referred to UK neurophysiology departments. AB - PURPOSE: To determine efficacy and safety of photic stimulation (PS) during electroencephalography (EEG) in a large group of adult and paediatric patients. METHODS: A prospective multicentre National Service Evaluation was performed organised by the joint audit committee of the two UK professional organisations (Association of Neurophysiological Scientists and British Society for Clinical Neurophysiology). Questionnaires about every EEG performed in the two-month study period were completed contemporaneously by physiologists at the time of the recording-reporting. The occurrence during PS of photoparoxysmal responses (PPRs), seizures and psychogenic non-epileptic attacks was noted from the EEG trace and contemporary clinical observation backed up by the video that was synchronised with the EEG. 5383 patients investigated with EEG and PS, mostly for possible epilepsy, were included in the study. RESULTS: Seventy nine patients (1.5%) had a generalised PPR elicited by PS having had no generalised epileptiform discharges previously in the EEG. Thirty nine patients (0.7%) had seizures provoked by PS including two (0.04%) who had a generalised tonic clonic seizure (GTCS). Forty nine patients (0.9%) had non-epileptic attacks provoked by PS. Thus PS yielded potentially useful information (PPRs, seizures or non epileptic attacks) in 167/5383 (3.1%) of patients. In a subset of 122/5383 (2.3%), PS provided the only useful information captured within the EEG. CONCLUSION: PS contributes to the diagnosis of epilepsy and non-epileptic attack disorder in 3.1% of patients. It is a safe technique which produces GTCSs in only 0.04% patients. We conclude that PS is a moderately useful activation technique in diagnostic EEG, where the potential benefits out-weigh the risks; this information may assist the informed consent process. PMID- 26667208 TI - Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery. AB - Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion. PMID- 26667209 TI - Epigenetic targets in cancer and aging: dietary and therapeutic interventions. AB - INTRODUCTION: Epigenetic regulation plays a critical role in normal growth and embryonic development by controlling the transcriptional activities of several genes. A growing number of epigenetic changes have been reported in the regulation of key genes involved in cancer and aging. Drugs with epigenetic modulatory activities, mainly histone deacetylase and DNA methyltransferase inhibitors, have received wider attention in aging and cancer research. AREAS COVERED: In this review, we summarize the major epigenetic alterations in cancer and aging, with special emphasis on possible therapeutic targets and interventions by dietary as well as bioactive phytochemicals. EXPERT OPINION: Some epigenetic-targeting drugs have received FDA approval and many others are undergoing different phases of clinical trials for cancer therapy. In addition to the synthetic compounds, several bioactive phytochemicals and dietary interventions, such as caloric restriction, have been shown to possess epigenetic modulatory activities in multiple cancers. These epigenetic modulators have been shown to delay aging and minimize the risk of cancer both in preclinical as well as clinical models. Therefore, knowledge of bioactive phytochemicals along with dietary interventions can be utilized for cancer prevention and therapy both alone and with existing drugs to achieve optimum efficacy. PMID- 26667210 TI - Control of overweight and obesity in childhood through education in meal time habits. The 'good manners for a healthy future' programme. AB - OBJECTIVE: Our aim is to determine the effect of paced eating, exposure to an educational programme that promotes healthy eating habits and allowing the satiety reflex to limit food intake in controlling weight gain in healthy adolescents. METHODS: Fifty-four healthy individuals consisting of 18 adolescent girls and 36 boys aged 12 +/- 2 years were given recommendations for reducing eating rate without changing diet or meal size according to the educational programme 'good manners for a healthy future'. Each participant was provided with a 30-s portable hourglass to pace time between bites. Individuals using and not using the hourglass were placed either into an 'adhering' or a 'non-adhering' group, respectively. Control data were obtained from a similar population. RESULTS: Initially, the adhering group had higher weight compared with the non adhering group (64.1 +/- 13.2 vs. 56.2 +/- 11.7 kg). Control group weight was no different from the study group at baseline (56.3 +/- 10.3 kg). Weight in the adhering group decreased after the first semester of participation by 2.0 +/- 5.7% and after a year by 3.4 +/- 4.8%, while the non-adhering group gained weight by 5.8 +/- 4.5% and 12.6 +/- 8.3%. The control group increased weight after a year by 8.2 +/- 6.5%. In total, 18 non-adhering and 14 adhering adolescents completed the study. CONCLUSIONS: This 1-year study shows a statistically significant association between rate of food intake and weight control in adherence to an educational programme directed at developing healthy eating habits. The proposed behavioural training may serve as an option for weight control in adolescents. PMID- 26667211 TI - Bone-formers and bone-losers in an archaeological population. AB - OBJECTIVES: Recent biomedical research suggests that, in modern human populations, individuals may vary in their inherent tendency toward bone formation at skeletal and extra-skeletal locations. However, the nature of this phenomenon is incompletely understood, and the extent to which it might apply to past populations is unclear. It is hypothesized that if there is inter-individual variation in some overall tendency toward bone formation in skeletal and extra skeletal sites then there should be a positive relationship between ligamentous ossification and thickness of cortical bone. This work is a test of this hypothesis in an archaeological population. MATERIALS AND METHODS: The study material comprises adult skeletons (N = 137 individuals) of documented age at death from 18th to 19th century London. It examines the relationship between bone deposition in the anterior longitudinal ligament (ALL) in the thoracic spine and cortical index (CI) at the metacarpal measured by radiogrammetry. RESULTS: Controlling for the potential confounders age, sex, skeletal completeness, occupation (males) and parity (females), there was a positive association between ossification into the ALL and CI. This reflects lesser medullary cavity width in those showing ALL ossification. DISCUSSION: Ligamentous ossification in the axial skeleton and peripheral cortical bone status are linked, individuals with ALL ossification showing lesser resorption of cortical bone at the endosteal surface. This is consistent with the idea of inter-individual variation in some general bone-forming/bone-losing tendency in this 200 year old study population, but there was no evidence of a link between ALL ossification and increased skeletal subperiosteal bone deposition. PMID- 26667212 TI - Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database. AB - OBJECTIVE: To evaluate performance of pelvic lymph node dissection during radical prostatectomy within an equal access care setting over a period of time, and stratified by prostate cancer risk group and surgical technique. METHODS: We identified men in the Shared Equal Access Regional Cancer Hospital database who had open or robotic-assisted radical prostatectomy from 2006 to 2013. Univariable logistic regression was used to test the association between age, race, body mass index, total biopsy cores, number of positive biopsy cores, risk group, year, center, surgical volume and surgical technique on pelvic lymph node dissection use. Multivariable logistic analysis was used to examine surgical technique and pelvic lymph node dissection performance. Spearman's correlation examined temporal changes in pelvic lymph node dissection utilization stratified by risk group and surgical technique. RESULTS: A total of 1425 men met inclusion criteria; 67% of them underwent pelvic lymph node dissection. On multivariable analysis, robotic-assisted radical prostatectomy was associated with an 92% decreased use of pelvic lymph node dissection in low-risk, 84% decreased in intermediate-risk and 91% decreased in high-risk men (all P < 0.001). In robotic assisted radical prostatectomy, there was a trend for increased pelvic lymph node dissection utilization over time in high-risk men (Spearman; P = 0.077) reaching ~85% in 2012-2013, which was accompanied by increased use in low-risk men (P = 0.016). For open radical prostatectomy, fewer pelvic lymph node dissections were carried out in low-risk men over time, decreasing to ~35% (P = 0.047) in 2012 2013, whereas rates remained high for high-risk men throughout (~95%; P = 0.621). CONCLUSION: Regardless of risk group, pelvic lymph node dissection is carried out significantly less during robotic-assisted radical prostatectomy. For robotic assisted radical prostatectomy, pelvic lymph node dissection utilization increased over time for high-risk men, but rates also increased for low-risk men. Further attention to the discrepancy between provided and guideline recommended pelvic lymph node dissection performance is required to improve prostate cancer care. PMID- 26667213 TI - Wnts talking with the TGF-beta superfamily: WISPers about modulation of osteoarthritis. AB - The Wnt signalling pathway is gaining increasing attention in the field of joint pathologies, attributable to its role in the development and homeostasis of the tissues found in the joint, including bone and cartilage. Imbalance in this pathway has been implicated in the development and progression of OA, and interference with the pathway might therefore depict an effective treatment strategy. Though offering multiple opportunities, it is yet to be decided which starting point will bring forth the most promising results. The complexity of the pathway and its interaction with other pathways (such as the TGF-beta signalling pathway, which also has a central role in the maintenance of joint homeostasis) means that acting directly on proteins in this signalling cascade entails a high risk of undesired side effects. Therefore, interference with Wnt-induced proteins, such as WISP1, might be an overall more effective and safer therapeutic approach to inhibit the pathological events that take place during OA. PMID- 26667214 TI - Real-life effectiveness of canakinumab in cryopyrin-associated periodic syndrome. AB - OBJECTIVE: Cryopyrin-associated periodic syndrome (CAPS) is a heterogeneous group of diseases characterized by excessive IL-1beta release resulting in severe systemic and organ inflammation. Canakinumab targets IL-1beta and is approved at standard dose for children and adults with all CAPS phenotypes. Limited data are available for the real-life effectiveness of canakinumab in patients living with CAPS. Therefore the aim of the study was to evaluate the real-life dosing and effectiveness of canakinumab in CAPS. METHODS: A multi-centre study of consecutive children and adults with CAPS treated with canakinumab was performed. Demographics, CAPS phenotype and disease activity, inflammatory markers and canakinumab treatment strategy were recorded. Treatment response was assessed using CAPS disease activity scores, CRP and/or serum amyloid A levels. Comparisons between age groups, CAPS phenotypes and centres were conducted. RESULTS: A total of 68 CAPS patients at nine centres were included. All CAPS phenotypes were represented. Thirty-seven (54%) patients were females, the median age was 25 years and 27 (40%) were children, and the median follow-up was 28 months. Overall, complete response (CR) was seen in 72% of CAPS patients, significantly less often in severe (14%) than in mild CAPS phenotypes (79%). Only 53% attained CR on standard dose canakinumab. Dose increase was more commonly required in children (56%) than in adults (22%). Centres with a treat-to-target approach had significantly higher CR rates (94 vs 50%). CONCLUSION: Real-life effectiveness of canakinumab in CAPS was significantly lower than in controlled trials. Treat-to-target strategies may improve the outcome of children and adults living with CAPS. PMID- 26667215 TI - Mannose binding lectin deficiency and susceptibility to infections in patients with rheumatoid arthritis. PMID- 26667217 TI - Abatacept efficacy in rheumatoid arthritis is dependent upon baseline blood B cell levels. PMID- 26667216 TI - Is salivary gland ultrasonography a useful tool in Sjogren's syndrome? A systematic review. AB - OBJECTIVE: Ultrasonography (US) is a sensitive tool in the diagnosis of major salivary gland abnormalities in primary Sjogren's syndrome (pSS). The aim of this systematic review was to assess the metric properties of this technique. METHODS: PUBMED and EMBASE databases were searched. All publications between January 1988 and January 2013 were considered. Data were extracted from the articles meeting the inclusion criteria according to US definition of salivary gland scoring system and metric properties studied. The type and number of glands tested, study design and metric properties according to OMERACT filter (truth, discrimination, feasibility) were assessed. RESULTS: Of 167 publications identified initially with PUBMED and EMBASE, 31 met the inclusion criteria. The number of pSS patients varied among the studies from 16 to 140. The diagnosis of pSS was in line in most of the cases with the American-European Consensus Group (AECG) classification criteria for Sjogren's syndrome. The US examination was performed in suspected pSS only in studies in which the sensitivity ranged from 45.8 to 91.6% and specificity from 73 to 98.1%. There was heterogeneity in regard to the definition of US in B-mode and few studies used US in colour Doppler. Few studies reported reliability of US and sensitivity to change in pSS. CONCLUSION: US is a valuable tool for detecting salivary gland abnormalities in pSS. Its reliability has been poorly investigated and there is considerable variation in the definition of US abnormalities. Further studies are required to validate and standardize the US definition of salivary gland in pSS. PMID- 26667218 TI - In vitro functional characterization of the Na+/H+ antiporters in Corynebacterium glutamicum. AB - Corynebacterium glutamicum, typically used as industrial workhorse for amino acid production, is a moderately salt-alkali-tolerant microorganism with optimal growth at pH 7-9. However, little is known about the mechanisms of salt-alkali tolerance in C. glutamicum. Here, the catalytic capacity of three putative Na(+)/H(+) antiporters from C. glutamicum (designated as Cg-Mrp1, Cg-Mrp2 and Cg NhaP) were characterized in an antiporter-deficient Escherichia coli KNabc strain. Only Cg-Mrp1 was able to effectively complement the Na(+)-sensitive of E. coli KNabc. Cg-Mrp1 exhibited obvious Na(+)(Li(+))/H(+) antiport activities with low apparent Km values of 1.08 mM and 1.41 mM for Na(+) and Li(+), respectively. The Na(+)/H(+) antiport activity of Cg-Mrp1 was optimal in the alkaline pH range. All three antiporters showed detectable K(+)/H(+) antiport activitiy. Cg-NhaP also exhibited Na(+)(Li(+),Rb(+))/H(+) antiport activities but at lower levels of activity. Interestingly, overexpression of Cg-Mrp2 exhibited clear Na(+)(K(+))/H(+) antiport activities. These results suggest that C. glutamicum Na(+)(K(+))/H(+) antiporters may have overlapping roles in coping with salt alkali and perhaps high-osmolarity stress. PMID- 26667219 TI - Aspergillus oerlinghausenensis, a new mould species closely related to A. fumigatus. AB - Two isolates belonging to Aspergillus section Fumigati were recovered from German soil on itraconazole containing agar media. Phylogenetic analysis and phenotypic characterization of both isolates show that they represent a novel species named Aspergillus oerlinghausenensis (holotype CBS H-22119(HT), ex-type CBS 139183(T) = IBT 33878 = DTO 316-A3). The species is phylogenetically related to A. fischeri and A. fumigatus. Aspergillus oerlinghausenensis can be differentiated from A. fischeri by its higher growth rate at 50 degrees C. Furthermore, A. oerlinghausenensis is protoheterothallic as only the MAT1-1 idiomorph was detected, while A. fischeri is homothallic. The species differs from A. fumigatus by a weak sporulation on malt extract agar at 25 degrees C, a floccose colony texture on Czapek yeast extract agar and malt extract agar and subglobose instead of subclavate vesicles. The cyp51A promoter region of A. oerlinghausenensis deviates from the previously reported cyp51A promoter regions in A. fumigatus and potentially presents a novel azole resistance conferring modification. Due to the close relationship of A. oerlinghausenensis with A. fischeri and A. fumigatus, this species is placed in a good position for comparative studies involving these species. PMID- 26667220 TI - Horizontal gene transfer of chromosomal Type II toxin-antitoxin systems of Escherichia coli. AB - Type II toxin-antitoxin systems (TAs) are small autoregulated bicistronic operons that encode a toxin protein with the potential to inhibit metabolic processes and an antitoxin protein to neutralize the toxin. Most of the bacterial genomes encode multiple TAs. However, the diversity and accumulation of TAs on bacterial genomes and its physiological implications are highly debated. Here we provide evidence that Escherichia coli chromosomal TAs (encoding RNase toxins) are 'acquired' DNA likely originated from heterologous DNA and are the smallest known autoregulated operons with the potential for horizontal propagation. Sequence analyses revealed that integration of TAs into the bacterial genome is unique and contributes to variations in the coding and/or regulatory regions of flanking host genome sequences. Plasmids and genomes encoding identical TAs of natural isolates are mutually exclusive. Chromosomal TAs might play significant roles in the evolution and ecology of bacteria by contributing to host genome variation and by moderation of plasmid maintenance. PMID- 26667221 TI - Mushroom tumor: a new disease on Flammulina velutipes caused by Ochrobactrum pseudogrignonense. AB - Mushroom tumor on Flammulina velutipes has become the main disease during the off season cultivation of F. velutipes while the causal organism has remained unknown. The present study was aimed at identifying the pathogen confirming its pathogenisity following Koch's Postulates, characterizing it using morphological, physiological, biochemical and molecular features, and studying its current distribution. We determined that mushroom tumor is a new bacterial infection disease caused by Ochrobactrum pseudogrignonense. It produces tumor-like structures on the surface of the substrate, and inhibits the formation of primordia and fruiting of F. velutipes. The molecular studies showed that this new pathogen is closely related to Ochrobactrum based on 16S rRNA sequences. This is the first time that Ochrobactrum has been shown to be a pathogen of a mushroom. PMID- 26667222 TI - Computer-aided planning and surgical guiding system fabrication in premolar autotransplantation: a 12-month follow up. AB - This case report describes the autotransplantation of maxillary right second premolar into the contralateral position in a 14-year-old female using computerized tomographic data and a customized guiding system produced by computer-aided design/computer-assisted manufacture technology. Using innovative surgical guides and keys with navigation features, modification of the recipient socket and handling of the transplant were facilitated without harming the periodontal membrane. Postoperative clinical and radiographic examination showed periodontal and pulp healing earlier than 6 months after surgery. PMID- 26667223 TI - Energy expenditure and growth failure after intestinal transplantation: A case report. AB - We present a 12-yr-old boy who received a combined liver-pancreas small bowel transplantation at the age of two. The post-operative period was complicated by wound closure problems resulting in a large asymptomatic abdominal wall defect. Further follow-up was uneventful, with the exception of new onset growth failure not explained by extensive routine investigations. An indirect calorimetry was performed. The resting energy expenditure (REE) was significantly increased (126% of predicted), demanding a daily caloric intake of 123 kcal/kg body weight (normal for age: 80 kcal/kg). In the absence of classic reasons for increased REE, a thermal camera revealed increased dermal heat loss at the abdominal wall defect (estimated surplus in energy loss of at least 29 kcal/day: 10.4% of the elevated REE). In addition, we found lower total lung capacity due to impaired abdominal breathing. In the exploration of growth failure in children after (ITx), increased REE must be taken into account. Indirect calorimetry can serve as a valuable diagnostic tool for evaluating individual energy requirements and nutritional support. In this child, exaggerated heat loss through an aberrant abdominal wall could be a potential important contributor to the patient's increased energy requirements. PMID- 26667225 TI - Correction. PMID- 26667224 TI - Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats, cats with chronic kidney disease, and cats with liver disease. AB - Ondansetron, a 5-HT3 receptor antagonist, is an effective anti-emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg (mean 0.49 mg/kg, range 0.27-1.05 mg/kg) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL.h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age-matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats. PMID- 26667226 TI - Nerve detection with optical spectroscopy for regional anesthesia procedures. AB - BACKGROUND: Regional anesthesia has several advantages over general anesthesia but requires accurate needle placement to be effective. To achieve accurate placement, a needle equipped with optical fibers that allows tissue discrimination at the needle tip based on optical spectroscopy is proposed. This study investigates the sensitivity and specificity with which this optical needle can discriminate nerves from the surrounding tissues making use of different classification methods. METHODS: Diffuse reflectance spectra were acquired from 1563 different locations from 19 human cadavers in the wavelength range of 400 1710 nm; measured tissue types included fascicular tissue of the nerve, muscle, sliding fat and subcutaneous fat. Physiological parameters of the tissues were derived from the measured spectra and part of the data was directly compared to histology. Various classification methods were then applied to the derived parameter dataset to determine the accuracy with which fascicular tissue of the nerve can be discriminated from the surrounding tissues. RESULTS: From the parameters determined from the measured spectra of the various tissues surrounding the nerve, fat content, blood content, beta-carotene content and scattering were most distinctive when comparing fascicular and non-fascicular tissue. Support Vector Machine classification with a combination of feature selections performed best in discriminating fascicular nerve tissue from the surrounding tissues with a sensitivity and specificity around 90 %. CONCLUSIONS: This study showed that spectral tissue sensing, based on diffuse reflectance spectroscopy at the needle tip, is a promising technique to discriminate fascicular tissue of the nerve from the surrounding tissues. The technique may therefore improve accurate needle placement near the nerve which is necessary for effective nerve blocks in regional anesthesia. PMID- 26667227 TI - Labeling quality and molecular characterization studies of products containing Lactobacillus spp. strains. AB - The objective of the study was to characterize at species level by phenotypic and different molecular methods the strains of Lactobacillus spp. used as constituents of five oral and four vaginal products. Susceptibilities to representative antibiotics were evaluated. In addition, total viable counts at mid and 3 months to deadline of shelf life, in the different formulations and the presence of eventual contaminant microorganisms were investigated.In all oral products the molecular characterization at species level of the strains of Lactobacillus spp. confirmed the strains stated on the label, except for one strain cited on the label as Lactobacillus casei, that our study characterized as Lactobacillus paracasei. In oral products total viable cell content complied with content claimed on the label. In three out four vaginal products (one product claimed "bacillo di Doderlein"), molecular characterization complied with the bacterial name stated on the label. Two vaginal products reported viable counts on the label that were confirmed by our study. The other vaginal products, which did not report bacterial counts on the label, showed a similar decrease of viable counts at different dates to deadline compared to the others. From all the tested products, contaminant microorganisms and acquired resistance to representative antibiotics by the probiotic strains were not detected. PMID- 26667228 TI - Cytological evaluation of breast lesions in symptomatic patients presenting to Kenyatta National Hospital, Kenya: a retrospective study. AB - BACKGROUND: Palpable breast lump, breast pain, and nipple discharge are common symptoms of breast disease. Breast cytology (fine-needle aspiration, nipple discharge smear, and touch preparation) accurately identifies benign, atypical, and malignant pathological changes in breast specimens. This study aims to determine the types of breast lesions diagnosed by breast cytology and assess the clinical adequacy of narrative reporting of breast cytology results. METHODS: Medical records of 390 patients presenting to breast or general surgery clinics in Kenyatta National Hospital, Nairobi, Kenya, between January 2010 and March 2014 were evaluated retrospectively. RESULTS: Of the 390 diagnosed breast lesions, 89.7% (n = 350) occurred in females, while 10.3% (n = 40) occurred in males, giving rise to a female-to-male ratio of 8.8:1. Neoplastic breast lesions (n = 296) comprised 75.9%, while non-neoplastic breast lesions (n = 94) comprised 24.1% of all diagnosed breast lesions. The neoplastic lesions were classified as 72.3% (n = 214) benign and 27.7% (n = 82) malignant, resulting in a benign-to malignant ratio of 2.6:1. Fibroadenoma (n = 136) and gynecomastia (n = 33) were the most frequently diagnosed breast lesions for women and men, respectively. CONCLUSIONS: Breast cytology effectively diagnosed neoplastic and non-neoplastic breast lesions. Neoplastic breast lesions occurred more frequently in women whereas non-neoplastic lesions occurred more frequently in men. To address the limitations associated with narrative reporting of breast cytology results, a synoptic reporting format incorporating the United Kingdom's National Health Service Breast Screening Programme's diagnostic categories (C1 to C5) is recommended for adoption by this hospital. PMID- 26667230 TI - Mass Effect Alone May Not Explain Pulmonary Vascular Pathology in Severe Congenital Diaphragmatic Hernia. AB - Congenital diaphragmatic hernia (CDH) and congenital pulmonary airway malformation (CPAM) are diseases in which chest-occupying lesions can result in severe pulmonary hypoplasia. However, significant postnatal mortality due to pulmonary hypertension (PH) is more often seen in patients with CDH. We analyzed prenatal echocardiographic parameters of pulmonary vascular pathology in these groups to understand whether PH in patients with CDH is secondary to a mass effect or to underlying disease. We analyzed pre- and postnatal characteristics of 26 patients with severe CDH and 23 patients with severe CPAM from 2009 to 2012. Severe mediastinal compression, indicated by a low cardiothoracic ratio, was evident in both groups. However, fetuses with severe CDH had smaller pulmonary arteries bilaterally and higher pulsatility indices in the ipsilateral lung than those with severe CPAM. Prenatal modified McGoon indices were significantly lower in patients with CDH versus CPAM. Consistent with these prenatal measurements, postnatal PH was seen more frequently in patients with CDH compared to CPAM. Patients with severe CDH have prenatal evidence of pulmonary vascular remodeling compared to patients with severe CPAM. These results suggest a multifactorial origin for PH in CDH and support the idea of using prenatal medical therapies to promote vascular remodeling in these patients. PMID- 26667229 TI - Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions. AB - Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses. PMID- 26667231 TI - Discovery and Optimization of 1-(4-chloro-3-(trifluoromethyl)- phenyl)-3-(2 (amino)pyridin-3-yl)ureas as Novel KDR Kinase Inhibitors. AB - Kinase insert Domain-containing Receptor (KDR) is one of the currently validated targets for anticancer drug discovery and development. Herein, a series of o amino-arylurea derivatives have been synthesized and evaluated for their kinase inhibitory activity. The optimization on the basis of biological screening and molecular modeling resulted in obvious increase in KDR kinase inhibitory activity compared with the hit compound. Eventually, we identified a potent inhibitor 5a of 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-((quinolin-4-ylmethyl) amino)pyridin-3-yl)urea scaffold against KDR (IC50 = 0.0689 uM), which can serve as good starting point for further KDR inhibitor optimization and development. PMID- 26667232 TI - Rupture of sinus of Valsalva aneurysm into the left ventricle after dissecting through the interventricular septum mimicking aortic regurgitation. PMID- 26667233 TI - Exogenous gibberellin altered morphology, anatomic and transcriptional regulatory networks of hormones in carrot root and shoot. AB - BACKGROUND: Gibberellins stimulate cell elongation and expansion during plant growth and development. Carrot is a root plant with great value and undergoes obvious alteration in organ size over the period of plant growth. However, the roles of gibberellins in carrot remain unclear. RESULTS: To investigate the effects of gibberelliins on the growth of carrot, we treated carrot plants with gibberellic acid 3 (GA3) or paclobutrazol (a gibberellin inhibitor). The results found that GA3 dramatically reduced the root growth but stimulated the shoot growth of carrot. It also significantly promoted xylem development in the tuberous root of carrot. In addition, transcript levels of genes related to gibberellins, auxin, cytokinins, abscisic acid and brassinolides were altered in response to increased or reduced gibberellins. CONCLUSIONS: The inhibited tuberous root growth but enhanced shoot growth in plants treated with GA3 can be principally attributed to the changes in the xylem development of carrot roots. Negative feedback regulation mechanism of gibberellin biosynthesis also occurred in response to altered gibberellin accumulation. Gibberellins may interact with other hormones to regulate carrot plant growth through crosstalk mechanisms. This study provided novel insights into the functions of gibberellins in the growth and development of carrot. PMID- 26667234 TI - Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients. AB - Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient's clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen's Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher's exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018-1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy. PMID- 26667235 TI - Mechanical mixtures of metal oxides and phosphorus pentoxide as novel precursors for the synthesis of transition-metal phosphides. AB - This study presents a new type of precursor, mechanical mixtures of metal oxides (MOs) and phosphorus pentoxide (P2O5) are used to synthesize Ni2P, Co2P and MoP phosphides by the H2 reduction method. In addition, this is first report of common solid-state P2O5 being used as a P source for the synthesis of metal phosphides. The traditional precursors are usually prepared via a complicated preparation procedure involving dissolution, drying and calcination steps. However, these novel MOs/P2O5 precursors can be obtained only by simple mechanical mixing of the starting materials. Furthermore, unlike the direct transformation from amorphous phases to phosphides, various specific intermediates were involved in the transformation from MOs/P2O5 to phosphides. It is worthy to note that the dispersions of Ni2P, Co2P and MoP obtained from MOs/P2O5 precursors were superior to those of the corresponding phosphides prepared from the abovementioned traditional precursors. It is suggested that the morphology of the as-prepared metal phosphides might be inherited from the corresponding MOs. Based on the results of XRD, XPS, SEM and TEM, the formation pathway of phosphides can be defined as MOs/P2O5 precursors -> complex intermediates (metals, metal phosphates and metal oxide-phosphates) -> metal phosphides. PMID- 26667236 TI - Prognostic factors and biomarkers of congenital obstructive nephropathy. AB - Congenital obstructive nephropathy (CON) is the leading cause of chronic kidney disease (CKD) in children. Anomalies of the urinary tract are often associated with abnormal nephrogenesis, which is compounded by obstructive injury and by maternal risk factors associated with low birth weight. Currently available fetal and postnatal imaging and analytes of amniotic fluid, urine, or blood lack predictive value. For ureteropelvic junction obstruction, biomarkers are needed for optimal timing of pyeloplasty; for posterior urethral valves, biomarkers of long-term prognosis and CKD are needed. The initial nephron number may be a major determinant of progression of CKD, and most patients with CON who progress to renal failure reach this point in adulthood, presumably compounded by episodes of acute kidney injury. Biomarkers of tubular injury may be of particular value in predicting the need for surgical intervention or in tracking progression of CKD, and must be adjusted for patient age. Discovery of new biomarkers may depend on "unbiased" proteomics, whereby patterns of urinary peptide fragments from patients with CON are analyzed in comparison to controls. Most promising are the analysis of urinary exosomes (restricting biomarkers to relevant tubular cells) and quantitative magnetic resonance imaging techniques allowing precise determination of nephron number and tubular mass. The greatest need is for large prospective multicenter studies with centralized biomarker sample repositories to follow patients with CON from fetal life through adulthood. PMID- 26667237 TI - Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. AB - BACKGROUND: Anemia is a major complication for patients on chronic dialysis. Erythropoietin is effective if iron is available, however unnecessary iron supplementation results in iron overload. Reticulocyte hemoglobin equivalent (Ret He) may be useful for assessing iron status. METHODS: A national retrospective cohort study including all children on chronic dialysis in New Zealand between 2007 and 2013, pairing Ret-He with demographic information, anemia indices, and markers of iron status. RESULTS: In 606 observations, we found a modest relationship between Ret-He and transferrin saturation (TSAT) (r = 0.34, p < 0.001) and a poor correlation between Ret-He and ferritin (r = 0.09, p = 0.04). There was a negative correlation between ferritin and hemoglobin (r = -0.14, p = 0.002), a weak positive correlation between TSAT and hemoglobin (r = 0.12, p = 0.007), and a modest positive correlation between Ret-He and hemoglobin (r = 0.22, p < 0.001). The diagnostic performance of Ret-He to detect absolute iron deficiency (cut-off value 28.9 pg, sensitivity 90 %, specificity 75 %, AUC 0.87) was good. CONCLUSIONS: Ret-He is a more relevant marker of iron status than ferritin and TSAT. This supports prospectively testing Ret-He to distinguish between iron deficiency and suboptimal erythropoietin dosing as competing causes for anemia. Ferritin is an unhelpful biomarker of iron deficiency in this setting. PMID- 26667238 TI - Vitamin K antagonists in children with central venous catheter on chronic haemodialysis: a pilot study. AB - BACKGROUND: To date, no study has investigated the use of vitamin K antagonists (VKA) in children undergoing chronic haemodialysis (HD) with a central venous catheter (CVC). METHODS: Consecutive patients aged <18 years with a newly placed tunnelled CVC for chronic HD were enrolled over a 3-year period. Children with active nephrotic syndrome or a history of venous thrombosis received warfarin (VKA group) with therapeutic target international normalised ratios of between 2.0 and 3.0. Patients at standard risk of CVC malfunction were not treated with VKA (standard group). The primary end-point was overall CVC survival. RESULTS: The VKA group consisted of nine patients (median age 10.6 years; range 1.2-15.3 years) with 11 CVC, and the standard group comprised eight patients (11.8 years; 6.1-17.3 years) with ten CVC. The 6- and 12-month CVC survival was significantly longer in the VKA group than in the standard group (100 vs. 60 % and 83.3 vs. 16.7 %, respectively; p < 0.05), with a median survival of 369 and 195 days, respectively (p < 0.05). None of the CVC in the VKA group required removal due to malfunction, as compared to four in the standard group. No major bleeding episodes occurred in either group. CONCLUSIONS: Therapy with VKA would appear to be safe in children on chronic HD and may improve CVC survival in patients at increased risk of CVC thrombosis. PMID- 26667239 TI - Theoretical studies on the reaction of mono- and ditriflate derivatives of 1,4:3,6-dianhydro-D-mannitol with trimethylamine--Can a quaternary ammonium salt be a source of the methyl group? AB - DFT studies on the mechanism of the formation of "gemini" quaternary ammonium salts in the reaction of 1,4:3,6-dianhydro-D-mannitol ditriflate derivative with trimethylamine and its subsequent conversion to tertiary amine through the methyl transfer reaction are discussed. Two alternative reaction pathways are presented in the gas phase and in ethanol. Additionally, the transformation of the monotriflate derivative of 1,4:3,6-dianhydro-D-mannitol into the single quaternary ammonium salt is presented. Two functionals (B3LYP, M062X) and two basis sets (6-31+G** and 6-311++G**) were used for the calculations. The effect of the substituent attached to the five-membered rings at the C2 (and/or C5) carbon atom on the activation barrier is described. The trimethylammonium group bond to the five-membered ring greatly reduces the activation barrier height. The preferred reaction pathway for the conversions was established. Including the London dispersion in the calculations increases the stabilization of all the points on the potential energy surface in relation to individual reactants. PMID- 26667240 TI - Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H(+),K(+)-ATPase at different pH. AB - The interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives (compound 1 (N, N-Dipropyl-1-(2-phenyl-4,5,6,7-tetrahydrobenzofuran-4 yl)-1H-1,2,3-triazole-4-methanamine) and 2 (1-(2-Phenyl-4,5,6,7 tetrahydrobenzofuran-4-yl)-4-(morpholin-4-ylmethyl)-1H-1,2,3-triazole)) with H(+),K(+)-ATPase at different pH were studied by induced-fit docking, QM/MM optimization and MM/GBSA binding free energy calculations of two forms (neutral and protonated form) of compounds. The inhibition activity of compound 1 is measured and almost unchanged at different pH, while the activity of compound 2 increases significantly with pH value decreased. This phenomenon could be explained by their protonated form percentages and the calculated binding free energies of protonated and neutral mixture of compounds at different pH. The binding free energy of protonated form is higher than that of neutral form of compound, and the protonated form could be a powerful inhibitor of H(+),K(+) ATPase. By the decomposed energy comparisons of residues in binding sites, Asp137 should be the key binding site to protonated form of compound because of the hydrogen bond and electrostatic interactions. These calculation results could help for further rational design of novel H(+),K(+)-ATPase inhibitors. PMID- 26667242 TI - Factors affecting communication in emergency departments: doctors and nurses' perceptions of communication in a trilingual ED in Hong Kong. AB - BACKGROUND: This study investigates clinicians' views of clinician-patient and clinician-clinician communication, including key factors that prevent clinicians from achieving successful communication in a large, high-pressured trilingual Emergency Department (ED) in Hong Kong. METHODS: Researchers interviewed 28 doctors and nurses in the ED. The research employed a qualitative ethnographic approach. The interviews were audio-recorded, transcribed, translated into English and coded using the Nvivo software. The researchers examined issues in both clinician-patient and clinician-clinician communication. Through thematic analyses, they identified the factors that impede communication most significantly, as well as the relationship between these factors. This research highlights the significant communication issues and patterns in Hong Kong EDs. RESULTS: The clinician interviews revealed that communication in EDs is complex, nuanced and fragile. The data revealed three types of communication issues: (1) the experiential parameter (i.e. processes and procedures), (2) the interpersonal parameter (i.e. clinicians' engagements with patients and other clinicians) and (3) contextual factors (i.e. time pressures, etc.). Within each of these areas, the specific problems were the following: compromises in knowledge transfer at key points of transition (e.g. triage, handover), inconsistencies in medical record keeping, serious pressures on clinicians (e.g. poor clinician-patient ratio and long working hours for clinicians) and a lack of focus on interpersonal skills. CONCLUSIONS: These communication problems (experiential, interpersonal and contextual) are intertwined, creating a complex yet weak communication structure that compromises patient safety, as well as patient and clinician satisfaction. The researchers argue that hospitals should develop and implement best-practice policies and educational programmes for clinicians that focus on the following: (1) understanding the primary causes of communication problems in EDs, (2) accepting the tenets and practices of patient-centred care, (3) establishing clear and consistent knowledge transfer procedures and (4) lowering the patient-to-clinician ratio in order to create the conditions that foster successful communication. The research provides a model for future research on the relationship between communication and the quality and safety of the patient safety. PMID- 26667241 TI - Quantitative Detection and Genotyping of Helicobacter pylori from Stool using Droplet Digital PCR Reveals Variation in Bacterial Loads that Correlates with cagA Virulence Gene Carriage. AB - BACKGROUND: Epidemiologic studies of the carcinogenic stomach bacterium Helicobacter pylori have been limited by the lack of noninvasive detection and genotyping methods. We developed a new stool-based method for detection, quantification, and partial genotyping of H. pylori using droplet digital PCR (ddPCR), which allows for increased sensitivity and absolute quantification by PCR partitioning. MATERIALS AND METHODS: Stool-based ddPCR assays for H. pylori 16S gene detection and cagA virulence gene typing were tested using a collection of 50 matched stool and serum samples from Costa Rican volunteers and 29 H. pylori stool antigen-tested stool samples collected at a US hospital. RESULTS: The stool-based H. pylori 16S ddPCR assay had a sensitivity of 84% and 100% and a specificity of 100% and 71% compared to serology and stool antigen tests, respectively. The stool-based cagA genotyping assay detected cagA in 22 (88%) of 25 stools from CagA antibody-positive individuals and four (16%) of 25 stools from CagA antibody-negative individuals from Costa Rica. All 26 of these samples had a Western-type cagA allele. Presence of serum CagA antibodies was correlated with a significantly higher load of H. pylori in the stool. CONCLUSIONS: The stool-based ddPCR assays are a sensitive, noninvasive method for detection, quantification, and partial genotyping of H. pylori. The quantitative nature of ddPCR-based H. pylori detection revealed significant variation in bacterial load among individuals that correlates with presence of the cagA virulence gene. These stool-based ddPCR assays will facilitate future population-based epidemiologic studies of this important human pathogen. PMID- 26667244 TI - Biomass-to-biocrude on a chip via hydrothermal liquefaction of algae. AB - Hydrothermal liquefaction uses high temperatures and pressures to break organic compounds into smaller fractions, and is considered the most promising method to convert wet microalgae feedstock to biofuel. Although, hydrothermal liquefaction of microalgae has received much attention, the specific roles of temperature, pressure, heating rate and reaction time remain unclear. We present a microfluidic screening platform to precisely control and observe reaction conditions at high temperature and pressure. In situ observation using fluorescence enables direct, real-time monitoring of this process. A strong shift in the fluorescence signature from the algal slurry at 675 nm (chlorophyll peak) to a post-HTL stream at 510 nm is observed for reaction temperatures at 260 degrees C, 280 degrees C, 300 degrees C and 320 degrees C (P = 12 MPa), and occurs over a timescale on the order of 10 min. Biocrude formation and separation from the aqueous phase into immiscible droplets is directly observed and occurs over the same timescale. The higher heating values for the sample are observed to increase over shorter timescales on the order of minutes. After only 1 minute at 300 degrees C, the higher heating value increases from an initial value of 21.97 MJ kg(-1) to 33.63 MJ kg(-1). The microfluidic platform provides unprecedented control and insight into this otherwise opaque process, with resolution that will guide the design of large scale reactors and processes. PMID- 26667243 TI - Age, anti-mullerian hormone, antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide. AB - BACKGROUND: A cohort study was performed to identify ovarian reserve markers (ORM) that predicts amenorrhea or oligomenorrhea 6 months after cyclophosphamide CTX in women with breast cancer. METHODS: 52 eumenorrheic patients with breast cancer were enrolled. FSH, anti-Mullerian hormone (AMH), antral follicles count (AFC) were measured before and 6 months after CTX. A logistic regression for independent samples and determination of the ROC curve were performed. RESULTS: The age of 32 years presented 96 % of sensitivity and 39 % of specificity to predict amenorrhea or oligomenorrhea with ROC area under the curve (AUC) of 0.77. ovarian reserve marker (ORM) with power to predict amenorrhea or oligomenorrhea in women after CTX were AMH <3.32 ng/mL (sensitivity of 85 %, specificity of 75 % and AUC 0.87), AFC <13 follicles (sensitivity 81 %, specificity 62 %, AUC 0.81). AMH cutoff to predict amenorrhea was 1.87 ng/mL (sensitivity 82 %, specificity 83 %, AUC 0.84) and AFC cutoff was 9 follicles (sensitivity 71 %, specificity 78 %, AUC 0.73). CONCLUSIONS: >=32-years-old women, AMH <3.32 ng/mL and AFC <13 follicles determined significantly higher risk of amenorrhea or oligomenorrhea after CTX with cyclophosphamide. The ORM age (>=32 years) analyzed together with AMH or AFC increases sensitivity and specificity in predicting amenorrhea or oligomenorrhea. PMID- 26667246 TI - Bisphosphonate drug holidays: we reap what we sow. PMID- 26667245 TI - Associations between adiposity, hormones, and gains in height, whole-body height adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children. AB - We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. INTRODUCTION: Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. METHODS: Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6 months from OPUS School Meal Study. RESULTS: In both sexes: gain in BAheight was positively associated with baseline FM (>=2.05 cm(2)/kg, both p <= 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (>=0.02 cm/ng/ml, p = 0.001) and osteocalcin (>=0.13 cm/ng/ml, p <= 0.009); and gain in BAheight was positively associated with baseline osteocalcin (>=0.35 cm(2)/ng/ml, p <= 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF 1 (0.06 cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/MUg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). CONCLUSIONS: This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize. PMID- 26667247 TI - Authors' reply to Upton. PMID- 26667248 TI - Psychiatrists' Comfort Using Computers and Other Electronic Devices in Clinical Practice. AB - This report highlights findings from the Study of Psychiatrists' Use of Informational Resources in Clinical Practice, a cross-sectional Web- and paper based survey that examined psychiatrists' comfort using computers and other electronic devices in clinical practice. One-thousand psychiatrists were randomly selected from the American Medical Association Physician Masterfile and asked to complete the survey between May and August, 2012. A total of 152 eligible psychiatrists completed the questionnaire (response rate 22.2 %). The majority of psychiatrists reported comfort using computers for educational and personal purposes. However, 26 % of psychiatrists reported not using or not being comfortable using computers for clinical functions. Psychiatrists under age 50 were more likely to report comfort using computers for all purposes than their older counterparts. Clinical tasks for which computers were reportedly used comfortably, specifically by psychiatrists younger than 50, included documenting clinical encounters, prescribing, ordering laboratory tests, accessing read-only patient information (e.g., test results), conducting internet searches for general clinical information, accessing online patient educational materials, and communicating with patients or other clinicians. Psychiatrists generally reported comfort using computers for personal and educational purposes. However, use of computers in clinical care was less common, particularly among psychiatrists 50 and older. Information and educational resources need to be available in a variety of accessible, user-friendly, computer and non-computer-based formats, to support use across all ages. Moreover, ongoing training and technical assistance with use of electronic and mobile device technologies in clinical practice is needed. Research on barriers to clinical use of computers is warranted. PMID- 26667249 TI - Separating the wheat from the chaff: region of interest combined with metal artifact reduction for completion angiography following cerebral aneurysm treatment. AB - INTRODUCTION: Following complicated endovascular or microsurgical treatments, assessment of radiographic outcome can be challenging due to device resolution and metallic artifact. Two-dimensional and three-dimensional angiography can reveal information about flow and aneurysm obliteration, but may be limited by beam hardening, overlapping vessels, and image degradation in the region of metallic implants. In this study, we investigated the combination of a collimated volumetric imaging (volume of interest, VOI) protocol followed by metal artifact reduction (MAR) post-processing to evaluate the correct positioning of stents, flow diverters, coils, and clips while limiting the radiation dose to the patient. METHODS: 9 patients undergoing 10 procedures were included in our study. All patients underwent endovascular or surgical treatment of a cerebral aneurysm involving stents, flow diverting stents, coils, and/or clips followed by either immediate or early postoperative evaluation of our protocol. RESULTS: Image datasets corrected for metallic artifacts (VOI-MAR) were judged to be better-a statistically significant finding-than image datasets only corrected for field of view truncation (VOI alone). Qualitatively, images were more interpretable and informative with regards to device position and apposition to the vessel wall for those cases involving a pipeline, and with regards to encroachment on the parent artery and possible residual aneurysm, in all cases. CONCLUSIONS: VOI acquisition combined with MAR post-processing provides for accurate and informative evaluation of cerebral aneurysm treatment while limiting the radiation dose to patients. PMID- 26667250 TI - Comparison of clinical outcomes in patients with acute ischemic strokes treated with mechanical thrombectomy using either Solumbra or ADAPT techniques. AB - PURPOSE: To compare rates of symptomatic intracranial hemorrhage (SICH) and good clinical outcome at 90 days in patients with ischemic strokes from anterior circulation emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy using either Solumbra or A Direct Aspiration first-Pass Thrombectomy (ADAPT) techniques. METHODS: We compared clinical characteristics, procedural variables, and clinical outcomes in patients with anterior circulation ELVOs treated with mechanical thrombectomy using either a Solumbra or ADAPT technique at our institution over a 38-month period. SICH was defined using the SITS-MOST criteria. A good clinical outcome was defined as a modified Rankin Scale score of 0-2 at 90 days. RESULTS: One hundred patients were included, 55 in the Solumbra group and 45 in the ADAPT group. Patients in the ADAPT group had higher National Institutes of Health Stroke Scale (NIHSS) (19.2 vs 16.8, p=0.02) and a higher proportion of internal carotid artery terminus thrombi (42.2% vs 20%, p=0.03) than patients in the Solumbra group. Patients in the ADAPT group had a trend toward a lower rate of SICH than patients in the Solumbra group (2.2% vs 12.7%, p=0.07). Patients in the ADAPT group had a significantly higher rate of good clinical outcome at 90 days than patients in the Solumbra group (55.6% vs 30.9%, p=0.015). Use of the ADAPT technique (OR 6 (95% CI 1.0 to 31.2), p=0.049) was an independent predictor of a good clinical outcome at 90 days in our cohort. CONCLUSIONS: In our cohort, the ADAPT technique was associated with significantly higher good clinical outcomes at 90 days in patients with acute ischemic stroke due to anterior circulation ELVOs treated with mechanical thrombectomy. PMID- 26667252 TI - Invited Commentary: Troubling Trends in Birth Weight. AB - Birth weight is a strong predictor of the health of newborns. Consequently, the report by Catov et al. in this issue of the Journal (Am J Epidemiol. 2016;183(1):15-23), in which they showed downward trends in birth weights in a Pittsburgh, Pennsylvania, hospital from 1997 to 2011, raises concerns. The widening gap reported between birth weights of babies born to white and African American women could correspond to a widening gap in actual health outcomes. However, if the relation between birth weight and health outcomes is not causal, these trends may be epiphenomena of limited concern. PMID- 26667251 TI - Race Disparities and Decreasing Birth Weight: Are All Babies Getting Smaller? AB - The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37-41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%-9.9%), whereas the number born large for their gestational ages decreased (8.9%-7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P < 0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (-3.78 vs. -1.88 per year; P for interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth. PMID- 26667253 TI - Catov et al. Respond to "Troubling Trends in Birth Weight". PMID- 26667254 TI - Seroepidemiology of Human Polyomaviruses in a US Population. AB - Polyomaviruses (PyV) are potentially tumorigenic in humans. However, limited data exist on the population seroprevalence of PyVs and individual characteristics that relate to seropositivity. Using multiplex serology, we determined the seroprevalence of 10 human PyVs (BK, JC, KI, WU, MCV, HPyV6, HPyV7, TSV, HPyV9, and HPyV10) among controls from a population-based skin cancer case-control study (n = 460) conducted in New Hampshire between 1993 and 1995. On a subset of participants (n = 194), methylation at CpG dinucleotides across the genome was measured in peripheral blood using the Illumina Infinium HumanMethylation27 BeadChip array (Illumina Inc., San Diego, California), from which lymphocyte subtype proportions were inferred. All participants were seropositive for at least 1 PyV, with seroprevalences ranging from 17.6% (HPyV9) to 99.1% (HPyV10). Seropositivity to JC, MCV, and HPyV7 increased with age. JC and TSV seropositivity were more common among men than among women. Smokers were more likely to be HPyV9-seropositive but MCV-seronegative, and HPyV7 seropositivity was associated with prolonged glucocorticoid use. Based on DNA methylation profiles, differences were observed in CD8-positive T- and B-cell proportions by BK, JC, and HPyV9 seropositivity. Our findings suggest that PyV seropositivity is common in the United States and varies by sociodemographic and biological characteristics, including those related to immune function. PMID- 26667256 TI - The problem resident behavior guide: strategies for remediation. AB - In 2012, the ACGME supplemented the core competencies with outcomes-based milestones for resident performance within the six competency domains. These milestones address the knowledge, skills, abilities, attitudes, and experiences that a resident is expected to progress through during the course of training. Even prior to the initiation of the milestones, there was a paucity of EM literature addressing the remediation of problem resident behaviors and there remain few readily accessible tools to aid in the implementation of a remediation plan. The goal of the "Problem Resident Behavior Guide" is to provide specific strategies for resident remediation based on deficiencies identified within the framework of the EM milestones. The "Problem Resident Behavior Guide" is a written instructional manual that provides concrete examples of remediation strategies to address specific milestone deficiencies. The more than 200 strategies stem from the experiences of the authors who have professional experience at three different academic hospitals and emergency medicine residency programs, supplemented by recommendations from educational leaders as well as utilization of valuable education adjuncts, such as focused simulation exercises, lecture preparation, and themed ED shifts. Most recommendations require active participation by the resident with guidance by faculty to achieve the remediation expectations. The ACGME outcomes-based milestones aid in the identification of deficiencies with regards to resident performance without providing recommendations on remediation. The Problem Resident Behavior Guide can therefore have a significant impact by filling in this gap. PMID- 26667255 TI - The Development of Extremely Preterm Infants Born to Women Who Had Genitourinary Infections During Pregnancy. AB - Gestational genitourinary infections, which have been associated with neurodevelopmental impairments among infants born near term, have not been studied among very preterm infants. The mothers of 989 infants born before 28 weeks of gestation were interviewed about urine, bladder, or kidney infections (UTIs) and cervical or vaginal infections (CVIs) during pregnancy, as well as other exposures and characteristics, and their charts were reviewed for the Extremely Low Gestational Age Newborns (ELGAN) Study (2002-2004). At 2 years of age, these infants underwent a neurodevelopmental assessment. Generalized estimating equation logistic regression models of developmental adversities were used to adjust for potential confounders. Infants born to women who reported a UTI were less likely than were others to have a very low Mental Development Index (adjusted odds ratio = 0.5; 95% confidence interval: 0.3, 0.8), whereas infants born to women who reported a CVI were more likely than others to have a low Psychomotor Development Index (adjusted odds ratio = 1.7; 95% confidence interval: 1.04, 2.7). In this high-risk sample, maternal gestational CVI, but not UTI, was associated with a higher risk of impaired motor development at 2 years of age. The apparent protective effect of UTI might be spurious, reflect confounding due to untreated asymptomatic bacteriuria among women who were not given a diagnosis of UTI, or reflect preconditioning. PMID- 26667257 TI - Hip fracture-triggered Takotsubo syndrome: what is its real prevalence? PMID- 26667258 TI - The Associations Between Body Mass Index, Smoking, and Alcohol Intake with Ovarian Volume in Midlife Women. AB - BACKGROUND: Despite the fact that ovarian volume is a marker of reproductive aging, there is little understanding of factors related to ovarian volume among aging women. The objective of this analysis was to examine the associations between body mass index (BMI), cigarette smoking, and alcohol intake with ovarian volume among midlife women. MATERIALS AND METHODS: Data were analyzed from 771 women (45-54 years of age at baseline) enrolled in the Midlife Women's Health Study, a cohort study that was initiated in 2006. At annual clinic visits, height and weight were measured, a transvaginal ultrasound was performed to measure ovarian volume, blood was drawn to measure hormone concentrations, and a comprehensive questionnaire was administered. Generalized linear models and repeated measures mixed models were conducted to examine the associations between BMI, cigarette smoking, and alcohol intake with ovarian volume, adjusting for age and race. RESULTS: Age was significantly and negatively associated with ovarian volume. However, BMI, smoking, and alcohol use were not associated with ovarian volume either when stratified by menopausal status or when adjusting for age and race. Estradiol, but not progesterone or testosterone, was significantly and positively associated with ovarian volume overall and among both white and black participants (p < 0.05). CONCLUSIONS: This study provides insight into the associations between BMI, smoking, and alcohol use with ovarian volume among midlife women. The findings are somewhat consistent with the published literature and, thus, indicate that these factors may not be clinically important in terms of ovarian volume during the menopausal transition. PMID- 26667259 TI - Guillain-Barre syndrome following oral polio vaccination. PMID- 26667260 TI - Emergency repair of inguinal hernia in the premature infant is associated with high direct medical costs. AB - PURPOSE: Inguinal hernia repair is frequently performed in premature infants. Evidence on optimal management and timing of repair, as well as related medical costs is still lacking. The objective of this study was to determine the direct medical costs of inguinal hernia, distinguishing between premature infants who had to undergo an emergency procedure and those who underwent elective inguinal hernia repair. METHODS: This cohort study based on medical records concerned premature infants with inguinal hernia who underwent surgical repair within 3 months after birth in a tertiary academic children's hospital between January 2010 and December 2013. Two groups were distinguished: patients with incarcerated inguinal hernia requiring emergency repair and patients who underwent elective repair. Real medical costs were calculated by multiplying the volumes of healthcare use with corresponding unit prices. Nonparametric bootstrap techniques were used to derive a 95 % confidence interval (CI) for the difference in mean costs. RESULTS: A total of 132 premature infants were included in the analysis. Emergency surgery was performed in 29 %. Costs of hospitalization comprised 65 % of all costs. The total direct medical costs amounted to ?7418 per premature infant in the emergency repair group versus ?4693 in the elective repair group. Multivariate analysis showed a difference in costs of ?1183 (95 % CI -1196; 3044) in favor of elective repair after correction for potential risk factors. CONCLUSION: Emergency repair of inguinal hernia in premature infants is more expensive than elective repair, even after correction for multiple confounders. This deserves to be taken into account in the debate on timing of inguinal hernia repair in premature infants. PMID- 26667261 TI - Investigating CD11c expression as a potential genomic biomarker of response to TNF inhibitor biologics in whole blood rheumatoid arthritis samples. AB - INTRODUCTION: Gene expression profiling is rapidly becoming a useful and informative tool in a much needed area of research. Identifying patients as to whether they will respond or not to a given treatment before prescription is not only essential to optimise treatment outcome but also to lessen the economic burden that such drugs can have on healthcare resources. In rheumatoid arthritis (RA), there is of yet no genetic/genomic biomarker which can accurately predict response to TNF inhibitor biologics prior to treatment, despite much interest in this area. Multiple studies have reported findings on potential candidate genes; however, due to relatively small sample sizes or lack of sufficient validation, results have been disappointingly inconsistent. The aim of this research was to further explore the predictive value of a previously reported association between CD11c expression and response to the TNF inhibitor biologics, adalimumab and etanercept. METHODS: Real-time qPCR was performed using whole blood RNA samples obtained from seventy-five rheumatoid arthritis patients about to commence treatment with a TNF inhibitor biologic drug, whose response status was determined at 3-month follow-up using the EULAR classification criteria. Relative quantification of CD11c using the comparative CT method outputted differential expression between good-responders and non-responders as a fold-change. RESULTS: Relative expression of CD11c in patients receiving TNF inhibitor biologics yielded a decrease of 1.025 fold in good-responders as compared to non-responders (p-value = 0.36). Upon stratification of patients dependent upon the specific drug administered, adalimumab or etanercept, similar findings to the full cohort were observed, decreases of 1.015 (p-value = 0.33) and 1.032 fold (p-value = 0.13) in good-responders compared to non-responders, respectively. CONCLUSION: The results from this study reveal that CD11c expression does not correlate with response to TNF inhibitor biologics when tested for within pre-treatment whole blood samples of rheumatoid arthritis patients. PMID- 26667262 TI - Combination of Aflibercept and Bromfenac Therapy in Age-Related Macular Degeneration: A Pilot Study Aflibercept and Bromfenac in AMD. AB - BACKGROUND Among many protocols for treatment of exudative AMD, combined therapy of anti-VEGF agents and non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an ideal alternative to monotherapy based on ranibizumab or bevacizumab. The aim of this study was to evaluate the effectiveness of aflibercept and bromfenac in the treatment of exudative AMD. MATERIAL AND METHODS The study was conducted on a group of 27 patients with exudative AMD who were administered intravitreal aflibercept and topical bromfenac (study group) once a month. Additional injections were administered up to 3 months after the third administration, depending on response to treatment. The control group consisted of subjects treated with aflibercept only. Visual acuity and anatomical outcomes in optical coherence tomography (OCT) were assessed at baseline visit, 4 months after the first dose, and 6 months after the start of the treatment. RESULTS Visual acuity improved over time in the study group and the differences between the groups were statistically significant. No statistically significant differences were found in OCT parameters. CONCLUSIONS Combined therapy of aflibercept and bromfenac in the treatment of wet AMD is more effective than single aflibercept therapy. PMID- 26667263 TI - Identifying Paracoccidioides phylogenetic species by PCR-RFLP of the alpha tubulin gene. AB - Paracoccidioidomycosis is an important systemic fungal infection that occurs throughout Latin America. The etiological agents comprise a species complex that includes two major groups: P. brasiliensis (including subgroups S1, PS2, and PS3) and P. lutzii. A great number of phenotypes may overlap, especially among closely related groups, discouraging the use of morphology alone for species recognition. To overcome this problem, here we propose identifying cryptic Paracoccidioides spp. using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the alpha-tubulin (TUB1) gene. In silico analysis of 90 TUB1 sequences led to the identification of two restriction enzymes with the potential to identify Paracoccidioides: Bcl I and Msp I. A portion of the TUB1 gene was amplified and double digested in vitro with the Bcl I and Msp I endonucleases, which generated four different electrophoretic patterns corresponding to the four main genetic groups: S1, PS2, and PS3 of P. brasiliensis and P. lutzii. The major P. brasiliensis group recognized was S1 (n = 17; 42.5%), followed by PS2 (n = 9; 22.5%) and PS3 (n = 6; 15%). A total of eight (20%) P. lutzii isolates were identified, mainly from midwestern Brazil. Our data revealed that TUB1-RFLP is an efficient, fast, and inexpensive tool for identifying Paracoccidioides spp., which may be directly applied to the molecular epidemiological studies of paracoccidioidomycosis. PMID- 26667264 TI - Discharge home after acute stroke: Differences between older and younger patients. AB - OBJECTIVE: To identify determinants for discharge destination of older (>= 70 years) and younger (< 70 years) acute stroke patients. DESIGN: Multicentre prospective cohort. PATIENTS: A total of 395 patients, within 7 days of clinically evaluated stroke, were included from 6 hospital stroke units. METHODS: The main outcome measure was discharge destination (home vs clinical rehabilitation). Independent variables were: demographic factors, stroke characteristics, functional impairments and disabilities, cognition, comorbidity, and premorbid social participation. Multivariate logistic regression analysis established the independent strength of the contribution of possible determinants to discharge destination. RESULTS: Seventy-six percent of younger patients were discharged home, compared with 63% of older patients. Most of the younger patients discharged to clinical rehabilitation (71%) had a spouse, whereas only 40% of the older age group discharged to clinical rehabilitation had a spouse. Multivariate analysis showed that, besides National Institutes of Health Stroke Scale and Barthel Index scores, having a spouse was an important determinant for discharge home in the older age group (adjusted odds ratio 4.77, 95% confidence interval 2.01-11.31), but not in the younger age group. CONCLUSION: The presence of a spouse is an additional important factor determining discharge home in older stroke patients. It is important to monitor and support informal caregivers in order to provide appropriate care for older community-dwelling stroke patients. PMID- 26667266 TI - Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer associated fibroblasts. AB - Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone acetyltransferase acetylates STAT3, which, in turn, upregulates and activates the DNMT3b DNA methyltransferase. DNMT3b methylates CpG sites of the SHP-1 phosphatase promoter, which abrogates SHP-1 expression, and results in constitutive phosphorylation of JAK1. Sustained JAK1/STAT3 signalling is maintained by DNA methyltransferase DNMT1. Consistently, in human lung and head and neck carcinomas, STAT3 acetylation and phosphorylation are inversely correlated with SHP-1 expression. Combined inhibition of DNMT activities and JAK signalling, in vitro and in vivo, results in long-term reversion of CAF associated proinvasive activity and restoration of the wild-type fibroblast phenotype. PMID- 26667268 TI - Integrating nurse researchers in clinical practice - a challenging, but necessary task for nurse leaders. AB - AIM: To create awareness among nurse leaders, of what they may need to consider, when integrating nurse researchers as advanced nurse practitioners (ANP) at PhD level among their staff. BACKGROUND: In a time of transition nurse leaders may be challenged by the change towards evidence-based clinical nursing, including integrating nurse researchers in ANP positions. METHODS: A collective case study including three ANPs took place at a large regional hospital in Denmark. The cases were first analysed by focusing on the generic features, functions and skills of ANPs, and second by focusing on the approaches to evidence-based practice seen in the cases. RESULTS: Regardless of same position, formal level of research expertise and overall responsibility, different approaches related to each ANPs professional profile, interest, academic ambitions and personality were seen. CONCLUSION: Nurse leaders must ensure a process where the content and expectations of the particular role are mutually clarified and adjusted to the individual ANP and to the specific context, in order to create a harmonious match. IMPLICATIONS FOR NURSING MANAGEMENT: In order to clarify expectations regarding the inclusion of nurse researchers as ANPs at PhD level, the paper provides firm recommendations that may guide the process. PMID- 26667267 TI - Heterogeneity in the spread and control of infectious disease: consequences for the elimination of canine rabies. AB - Understanding the factors influencing vaccination campaign effectiveness is vital in designing efficient disease elimination programmes. We investigated the importance of spatial heterogeneity in vaccination coverage and human-mediated dog movements for the elimination of endemic canine rabies by mass dog vaccination in Region VI of the Philippines (Western Visayas). Household survey data was used to parameterise a spatially-explicit rabies transmission model with realistic dog movement and vaccination coverage scenarios, assuming a basic reproduction number for rabies drawn from the literature. This showed that heterogeneous vaccination reduces elimination prospects relative to homogeneous vaccination at the same overall level. Had the three vaccination campaigns completed in Region VI in 2010-2012 been homogeneous, they would have eliminated rabies with high probability. However, given the observed heterogeneity, three further campaigns may be required to achieve elimination with probability 0.95. We recommend that heterogeneity be reduced in future campaigns through targeted efforts in low coverage areas, even at the expense of reduced coverage in previously high coverage areas. Reported human-mediated dog movements did not reduce elimination probability, so expending limited resources on restricting dog movements is unnecessary in this endemic setting. Enhanced surveillance will be necessary post-elimination, however, given the reintroduction risk from long distance dog movements. PMID- 26667269 TI - A comparative physicochemical, morphological and magnetic study of silane functionalized superparamagnetic iron oxide nanoparticles prepared by alkaline coprecipitation. AB - The characterization of synthetic superparamagnetic iron oxide nanoparticle (SPION) surfaces prior to functionalization is an essential step in the prediction of their successful functionalization, and in uncovering issues that may influence their selection as magnetically targeted drug delivery vehicles (prodrugs). Here, three differently functionalized magnetite (Fe3O4) SPIONs are considered. All were identically prepared by the alkaline coprecipitation of Fe(2+) and Fe(3+) salts. We use X-ray photoelectron spectroscopy, electron microscopy, time-of-flight SIMS, FTIR spectroscopy and magnetic measurements to characterize their chemical, morphological and magnetic properties, in order to aid in determining how their surfaces differ from those prepared by Fe(CO)5 decomposition, which we have already studied, and in assessing their potential use as drug delivery carriers. PMID- 26667270 TI - Macrophages play an essential role in the long effects of low-dose photodynamic therapy on vessel permeability. AB - Low-dose photodynamic therapy (L-PDT) has been used to transiently increase the permeability of tumor vessels to improve the delivery of chemotherapeutic drugs to lung tumors. However, the effects of L-PDT in a long-term on delivery of chemotherapeutic drugs are unknown. In this study, we studied this question as well as the underlying mechanisms. We found that the effects of L-PDT on tumor vessel permeability appeared to be prolonged. Moreover, L-PDT significantly increased the number of tumor associated macrophages, and appeared to induce macrophage polarization to a M1 phenotype. Further analyses showed that L-PDT upregulated stromal cell-derived factor 1 (SDF-1) in tumor to recruit macrophages through a SDF-1/Chemokine (C-X-C Motif) Receptor 4 (CXCR4) axis, which accounted for the prolonged effects of L-PDT on vessel permeability. Application of a specific CXCR4 inhibitor significantly suppressed the L-PDT-induced macrophage recruitment, resulting in abolishment of the prolonged effects of L-PDT on vessel permeability. Furthermore, the inhibitory effects of LiporubicinTM on the growth of the implanted tumor in L-PDT-treated mice were significantly attenuated by CXCR4 inhibition. Thus, our data demonstrate a previously unappreciated long lasting effect of L-PDT on vessel permeability, and suggest that this long lasting effects of L-PDT treatment on vessel permeability may result from modulation of macrophage recruitment and polarization. Hence, L-PDT may be a promising method to assist chemotherapeutic approaches. PMID- 26667272 TI - Biology, Ecology, and Management of the Diamondback Moth in China. AB - The diamondback moth (DBM), Plutella xylostella (L.), costs the Chinese economy US$0.77 billion annually, and considerable research has focused on its biology, ecology, and management. Much of this research has been published locally and is inaccessible outside China. Since 1990 Brassica vegetable production has increased 20-fold and production practices have intensified, but losses continue to increase. Insecticide use is widespread and many DBM populations, particularly in southern provinces, are resistant to multiple compounds. The molecular bases of several insecticide resistance mechanisms are well understood, and genetic studies suggest that insecticide-resistant populations migrate northward in spring and that back migrations may occur in southern provinces. Fundamental studies have improved our understanding of the effects of temperature on DBM population dynamics and distributions and of interactions between DBM and its well-established parasitoid fauna. Nationally coordinated research is developing regional management strategies that integrate locally appropriate biological, physical, cultural, and insecticidal control, but sustaining their adoption will prove an enormous challenge. PMID- 26667273 TI - Hearing in Insects. AB - Insect hearing has independently evolved multiple times in the context of intraspecific communication and predator detection by transforming proprioceptive organs into ears. Research over the past decade, ranging from the biophysics of sound reception to molecular aspects of auditory transduction to the neuronal mechanisms of auditory signal processing, has greatly advanced our understanding of how insects hear. Apart from evolutionary innovations that seem unique to insect hearing, parallels between insect and vertebrate auditory systems have been uncovered, and the auditory sensory cells of insects and vertebrates turned out to be evolutionarily related. This review summarizes our current understanding of insect hearing. It also discusses recent advances in insect auditory research, which have put forward insect auditory systems for studying biological aspects that extend beyond hearing, such as cilium function, neuronal signal computation, and sensory system evolution. PMID- 26667274 TI - Major Hurdles for the Evolution of Sociality. AB - Why do most animals live solitarily, while complex social life is restricted to a few cooperatively breeding vertebrates and social insects? Here, we synthesize concepts and theories in social evolution and discuss its underlying ecological causes. Social evolution can be partitioned into (a) formation of stable social groups, (b) evolution of helping, and (c) transition to a new evolutionary level. Stable social groups rarely evolve due to competition over food and/or reproduction. Food competition is overcome in social insects with central-place foraging or bonanza-type food resources, whereas competition over reproduction commonly occurs because staying individuals are rarely sterile. Hence, the evolution of helping is shaped by direct and indirect fitness options and helping is only altruism if it reduces the helper's direct fitness. The helper's capability to gain direct fitness also creates within-colony conflict. This prevents transition to a new evolutionary level. PMID- 26667271 TI - Reproduction-Immunity Trade-Offs in Insects. AB - Immune defense and reproduction are physiologically and energetically demanding processes and have been observed to trade off in a diversity of female insects. Increased reproductive effort results in reduced immunity, and reciprocally, infection and activation of the immune system reduce reproductive output. This trade-off can manifest at the physiological level (within an individual) and at the evolutionary level (genetic distinction among individuals in a population). The resource allocation model posits that the trade-off arises because of competition for one or more limiting resources, and we hypothesize that pleiotropic signaling mechanisms regulate allocation of that resource between reproductive and immune processes. We examine the role of juvenile hormone, 20 hydroxyecdysone, and insulin/insulin-like growth factor-like signaling in regulating both oogenesis and immune system activity, and propose a signaling network that may mechanistically regulate the trade-off. Finally, we discuss implications of the trade-off in an ecological and evolutionary context. PMID- 26667275 TI - Traumatic Myiasis: A Neglected Disease in a Changing World. AB - Traumatic myiasis, the parasitic infestation by fly larvae in traumatic lesions of the tissues of living vertebrates, is a serious medical condition in humans and a welfare and economic issue in domestic animals. New molecular studies are providing insights into its evolution and epidemiology. Nevertheless, its incidence in humans is generally underreported, particularly in tropical and subtropical regions. Myiasis in domestic animals has been studied more extensively, but continuous management is difficult and expensive. A key concern is the inadvertent introduction and global spread of agents of myiasis into nonendemic areas, facilitated by climate change and global transport. The incursion of the New World screwworm fly (Cochliomyia hominivorax) into Libya is the most notable of many such range shifts and demonstrates the potential risks of these parasites and the costs of removing them once established in a geographic area. Nevertheless, the insect agents of myiasis can be of societal benefit to forensic science and in medicine as an aid to wound treatment (larval therapy). PMID- 26667276 TI - Particulates vs. fibers: dimension featured magnetic and visible light driven photocatalytic properties of Sc modified multiferroic bismuth ferrite nanostructures. AB - We report the magnetic and visible light driven photocatalytic properties of scandium (Sc) substituted bismuth ferrite (BSFO) particulate and fiber nanostructures. An increasing concentration of Sc was found to reduce the crystallite size, particle size and band gap energy of the BSFO nanostructures, which was evident from X-ray diffraction, field emission scanning electron microscopy and UV-Visible diffuse reflectance spectroscopy analysis respectively. The temperature dependent magnetic studies carried out using a SQUID magnetometer suggested that the origin of the magnetic properties in the pure BFO system could be the emergence of an antiferromagnetic-core/ferromagnetic-shell like structure, in contrast to the modified spin canted structures in the case of the BSFO nanostructures. The observed photocatalytic efficiency was attributed to the enhanced band bending process and recombination resistance in the BSFO nanostructures. For a comparative study, the photocatalytic activities of some selected compositions were also investigated under simulated solar light along with natural solar light. PMID- 26667277 TI - Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia. AB - Many neuropsychiatric disorders are marked by abnormal behaviour and decision making, but prevailing diagnostic criteria for such behaviours are typically qualitative and often ambiguous. Behavioural variant frontotemporal dementia and semantic variant primary progressive aphasia (also called semantic dementia) are two clinical variants of frontotemporal dementia with overlapping but distinct anatomical substrates known to cause profound changes in decision-making. We investigated whether abnormal decision-making in these syndromes could be more precisely characterized in terms of dissociable abnormalities in patients' subjective evaluations of valence (positive versus negative outcome) and of time (present versus future outcome). We presented 28 patients with behavioural variant frontotemporal dementia, 14 patients with semantic variant primary progressive aphasia, 25 patients with Alzheimer's disease (as disease controls), and 61 healthy older control subjects with experimental tasks assaying loss aversion and delay discounting. In general linear models controlling for age, gender, education and Mini-Mental State Examination score, patients with behavioural variant frontotemporal dementia were less averse to losses than control subjects (P < 0.001), while patients with semantic variant primary progressive aphasia discounted delayed rewards more steeply than controls (P = 0.019). There was no relationship between loss aversion and delay discounting across the sample, nor in any of the subgroups. These findings suggest that abnormal behaviours in neurodegenerative disease may result from the disruption of either of two dissociable neural processes for evaluating the outcomes of action. More broadly, these findings suggest a role for computational methods to supplement traditional qualitative characterizations in the differential diagnosis of neuropsychiatric disorders. PMID- 26667278 TI - Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis. AB - Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed single cortical projection neurons in autopsies from eight patients with long-standing relapsing-remitting or secondary progressive multiple sclerosis and eight control patients without neurological disease. Analysis of several hundred individual neurons located in the insular, frontotemporal and occipital lobe revealed a widespread and pronounced loss of dendritic spines in multiple sclerosis cortex that occurs independent of cortical demyelination and axon loss. The presence of a primary synaptic pathology in the normal-appearing cortex of multiple sclerosis patients challenges current disease concepts and has important implications for our understanding of disease progression. PMID- 26667281 TI - Axial myopathy: an overlooked feature of muscle diseases. AB - Classically, myopathies are categorized according to limb or cranial nerve muscle affection, but with the growing use of magnetic resonance imaging it has become evident that many well-known myopathies have significant involvement of the axial musculature. New disease entities with selective axial muscle involvement have also been described recently, but overall the axial myopathy is unexplored. We performed a PubMed search using the search terms 'myopathy', 'paraspinal', 'axial' and 'erector'. Axial myopathy was defined as involvement of paraspinal musculature. We found evidence of axial musculature involvement in the majority of myopathies in which paraspinal musculature was examined. Even in diseases named after a certain pattern of non-axial muscle affection, such as facioscapulohumeral and limb girdle muscular dystrophies, affection of the axial musculature was often severe and early, compared to other muscle groups. Very sparse literature evaluating the validity of clinical assessment methods, electromyography, muscle biopsy and magnetic resonance imaging was identified and reference material is generally missing. This article provides an overview of the present knowledge on axial myopathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. PMID- 26667279 TI - Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease. AB - Alzheimer's disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer's disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-beta oligomers, by mouse brain Alzheimer's disease transgenes or by human Alzheimer's disease pathology. Amyloid-beta oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp-Grm5 genetic interaction, being absent in transheterozygous loss-of function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer's disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer's disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID- 26667283 TI - Yoga Therapy Research: A Whole-Systems Perspective on Comparative Effectiveness and Patient-Centered Outcomes. AB - For the yoga research community to capitalize on its current momentum, it is critical to consider certain developments in research theory and innovative methodologies. The concept of model validity must be incorporated in yoga therapy research so that explanatory constructs employed and outcome measures chosen reflect the principles of traditional yogic science. Focusing on effectiveness research will ensure maximum generalizability of study results and reflect real world therapy delivery settings, thereby increasing the relevance of outcomes. Whole systems of healing require research methodologies that address complex relationships between multi-target therapies with multiple potential treatment results. Complex, dynamic systems theory provides the theoretical and methodological innovations necessary to design studies, choose outcomes, and analyze data in a way that can account for charting complex, cyclical, therapeutic trajectories across time. Emphasizing patient-centered outcomes is aligned with the patent-oriented and tailored natured of yoga therapy delivery. Increasing the quality and quantity of comparative effectiveness research to analyze the harms and benefits of contrasting therapies can provide an infrastructure for designing studies that can have significant practical impact. The creation of practice-based research networks within the yoga research community will incentivize links between mainstream clinical researchers and yoga therapy delivery settings, ultimately developing collaborative networks. Yoga therapy centers can facilitate patient recruitment for studies and inform standards for yoga researchers. Collaborative efforts between the yoga and ayurvedic research communities will streamline efforts, solidify expertise, cross pollinate theoretical and methodological innovation, and consolidate efforts to secure research funding and increase publication and dissemination of study findings. PMID- 26667284 TI - Yoga Therapy: Building a Holding Environment for Somatic and Psyche Change. AB - Drawing on ideas from D.W. Winnicott and the work of Quaker theologian Parker Palmer, this article discusses the concept of a holding environment, its refined understanding in the literature over the years, and how it can be optimally used in yoga therapy. The evidence shows that effectively establishing a holding environment can facilitate both somatic and deep structural change in a client, facilitating healing from primal wounding as well as the potential reconnection to the true self. PMID- 26667280 TI - Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. AB - White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia. PMID- 26667285 TI - Why Ayurvedic Yoga Therapists and Why Now? AB - IAYT has paved the way for yoga therapy as a healing profession to grow and develop its mission to deliver optimal therapeutics via individual sessions and tailored group classes. For the past five years, the National Ayurvedic Medical Association (NAMA) has been working behind the scenes to consider the value and definition of an ayurvedic yoga therapist (AYT) professional designation within the yoga therapy discipline. The AYT designation would complement the current standards for yoga therapists that have been published by IAYT. The purpose of this paper is to discuss (1) why the AYT designation is important; (2) how it supports and expands on IAYT's mission; and (3) why now is the appropriate time to develop competencies, standards, and a scope of practice for ayurvedic yoga therapy. PMID- 26667286 TI - Yoga Research and Spirituality: A Case Study Discussion. AB - There is growing evidence that yoga can be beneficial as an aspect of self-care for people with arthritis. However, yoga may be less acceptable to those from different cultures, socioeconomic backgrounds, and racial/ethnic identities. While implementing a feasibility/acceptability pilot study of yoga as self-care in minority communities, the subject of spirituality surfaced. This commentary shares the experience of the researchers and yoga teachers collaborating on the study and the larger conversation that ensued following the withdrawal of one of the study participants. It is an attempt to start a relevant and needed dialogue around yoga research as an integrative health modality, and why the underlying body-mind-spirit approach to yoga may sometimes serve as a barrier to participation for diverse populations suffering from arthritis. PMID- 26667287 TI - The Path from Yoga Therapy in a Medical School to a School of Yoga Therapy in an Integrative Medicine Department. AB - We describe how yoga therapy was established within a medical school. Additionally, this paper outlines the development of a yoga therapy position as well as the implementation of a school of yoga therapy in a university-based teaching hospital. PMID- 26667288 TI - Incorporating Yoga Therapy into Primary Care: The Casey Health Institute. AB - Individuals seek complementary and alternative medicine (CAM) for a variety of health conditions, and yoga is a popular CAM modality. Over the past few decades, yoga has become incorporated into hundreds of healthcare facilities, most commonly in large university medical centers. While research has shown yoga to be effective in reducing symptoms and improving outcomes in chronic health conditions, most patients seek yoga therapy on their own, as few primary care practitioners have incorporated yoga therapy into their practices. The purpose of this article is to describe the efforts of the Casey Health Institute to incorporate yoga therapy into their primary care integrative medicine center. At Casey Health, a full-time Clinical Yoga Specialist works alongside the physicians, nurses, and CAM providers in delivering care to a wide variety of patients. The majority of referrals to yoga therapy have been for pain-related musculoskeletal conditions, as well as hypertension, headaches, anxiety, depression, and sleep disturbances. Most patients attend weekly 60-minute individual sessions, and the Clinical Yoga Specialist stays in touch with the patient between appointments via telephone and email. T h e Clinical Yoga Specialist has become an integral part of Casey Health, participating in collaborative medical appointments in which two CAM practitioners provide simultaneous treatments to a patient. She also participates in the clinic's ongoing weight loss program. The Clinical Yoga Specialist spends one morning each week "floating" in the clinic, when she is on-call to the practitioners to assist in treatment and/or to introduce a yoga therapy experience to the patients. These brief interventions introduce the patients to the therapeutic benefits of yoga, while simultaneously demonstrating yoga's effectiveness to the healthcare providers. Casey Health has developed a unique teacher training program whose faculty includes senior Iyengar yoga teachers as well as physicians and CAM practitioners. Casey Health is incorporating clinical outcomes into their electronic medical record that can be used internally to assess comparable effectiveness and cost effectiveness of the different treatment modalities such as yoga therapy, providing evidence that eventually may lead to yoga therapy becoming an accepted treatment that is eligible for insurance reimbursement. PMID- 26667289 TI - The Essential Properties of Yoga Questionnaire: Development and Methods. AB - Yoga interventions have considerable heterogeneity, are multi-dimensional, and may impact health in different ways. However, most research reports regarding the effects of yoga on health and wellbeing do not adequately describe the components of the yoga interventions being used. Thus, drawing comparisons across studies or understanding the relative effects of specific aspects of a yoga intervention are rarely possible. To address this problem, we created the Essential Properties of Yoga Questionnaire (EPYQ) Project, an NCCAM-funded set of studies to develop a translational tool for yoga researchers. Here we describe the methods and developmental processes used in the EPYQ Project in detail. The project consists of four main phases. Phase I was designed to gain a comprehensive understanding of the relevant aspects of yoga by conducting a comprehensive systematic literature review and conducting focus groups with stakeholders including a wide variety of yoga teachers and students. In Phase II, a pool of potential questionnaire items was developed for the prototypic questionnaire using information from Phase I. Cognitive interviews were conducted with the preliminary EPYQ items to assess the perceived clarity, meaning, and importance of each item. In Phase III, the prototypic questionnaire was administered to two large samples of yoga students and instructors. Military personnel and veterans who practiced or taught yoga (n = 329) were recruited to participate. Factor analysis and item response theory were used to identify factors and select the final questionnaire items. Phase IV is ongoing and will collect reliability and validity data on the final instrument. Results are expected to be available in 2016. The EPYQ will provide an objective tool for describing the amount of various components of yoga interventions, eventually allowing researchers to link specific yoga components to health benefits, and facilitating the design of yoga interventions for specific health conditions. PMID- 26667290 TI - A Yoga Stress Reduction Intervention for University Faculty, Staff, and Graduate Students. AB - Yoga can be an effective intervention for physical and psychological symptoms and decreased ability to cope with physical, emotional, vocational, or academic stress. One group of individuals challenged regarding adequate self-care in the face of stress are personnel in university training programs for helping professions (e.g., psychology, nursing, nutrition). This feasibility study explored engagement in and effectiveness of a systematic 10-week yoga program aimed at university faculty, staff, and students. The intervention consisted of 10 weekly 90-minute sessions that were structured to include conceptual grounding, breathing, postures, and meditation. Weekly class outlines were made available to students for home practice. Participants signed informed consents, liability waivers, and health screenings. Self-reports of home practice, barriers to practice, perceived stress, and stress symptoms were used to evaluate whether the intervention was successful in engaging participants and reducing stress related symptoms. Engagement was demonstrated by study adherence in the first 10 week series (88%; 44 of 50 enrolled), as well as re-enrollment for at least one additional 10-week series (64%; 28 of 44). Intervention success was demonstrated through repeated measure s ANOVAs of 44 participants' data, which showed significant improvement after a single 10-week series in perceived stress, as well as self-reported psychological, behavioral, and physical symptoms of stress. The study demonstrates feasibility of a yoga intervention in an academic setting and provides preliminary evidence for efficacy in stress reduction. It also supplies 10 detailed session protocols for intervention replication. PMID- 26667291 TI - The Effects of Mindfulness-Based Movement on Parameters of Stress. AB - The Mindfulness-Based Stress Reduction program (MBSR) of Kabat-Zinn includes a combination of sitting meditation, yoga, and walking; thus, movement is not emphasized primarily to induce a state of awareness. The purpose of this study was to investigate the effects of a Mindfulness-Based Movement Program (MBM) in women on parameters of stress and coping; that is, in contrast to MBSR, MBM primarily emphasized yoga to cultivate awareness. This study investigated: (a) an objective measure of stress (the cortisol response to a laboratory stressor) following an 8-week MBM in year 1 participants only (n = 17; MBM group = 9; Control group = 8); (b) subjective measures of stress following an 8-week MBM in years 1 and 2 (n = 32; MBM = 16; C = 16); and (c) changes in coping style following an 8- week MBM in years 1 and 2 (n = 32; MBM = 16; C = 16). A mixed plot 2 (Group: TC or MBM) by 5 (Trial: Baseline, Stressor, Recovery 1, Recovery 2, and Recovery 3) repeated measures ANOVA was run for cortisol. Preliminary results indicated a strong trend towards a lowered cortisol response for the MBM group compared to the control group. A mixed plot 2 (Group: TC or MBM) by 2 (Time: Pretest, Post-test) repeated measures ANOVA was run for Spielberg's State Anxiety, the Perceived Stress Scale, and the Problem Focused Style of Coping Scale for the Suppressive, Reflective, and the Reactive Coping Style. There were significant main effects for time, group, and an interaction of time and group for Spielberg's State Anxiety and the Perceived Stress Scale. Significant differences were also found for time and the interaction of time and group for the Problem Focused Style of Coping for the Reflective Coping Style (p < 0.05). In conclusion, results indicate positive effects of the MBM program on perceived measures of stress and coping style in women. PMID- 26667292 TI - Efficacy of a Satyananda Yoga Intervention for Reintegrating Adults Diagnosed with Posttraumatic Stress Disorder. AB - The prevalence of posttraumatic stress disorder (PTSD) in ex-combatants from illegal armed groups in Colombia has been estimated at 37.4%. This high prevalence indicates a need to explore alternative and adjunctive therapies in the treatment of PTSD. A randomized controlled trial was undertaken to evaluate the efficacy and safety of a protocol based on Satyananda Yoga(r) in PTSD diagnosed reintegrating adults in Colombia. One hundred reintegrating adults (n = 50 for each of the yoga and control arms) from Bogota and Medellin participated in this study. Yoga participants engaged in a Satyananda Yoga intervention for 16 weeks while the control group continued the regular demobilization program. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) was used to evaluate the effects of the applied therapy. Outcomes were assessed before entry and after the treatment. T-tests revealed a treatment effect of d = 1.15 for the yoga group and a between-groups effect size of d = .73. The difference in improvement in PCL-C scores between both groups was 18.91% (p < 0.05). The highest percentage of improvement was observed in the re-experiencing symptom cluster (23.71%; p < 0.05), with a treatment effect of d = 1.40 for the yoga group and a between-groups effect size of d = 1.15. The data suggest that Satyananda Yoga methodology is an effective therapy for reintegrating adults diagnosed with PTSD. Further research is needed in order to evaluate prolonged effects of this alternative therapy. PMID- 26667293 TI - Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease. AB - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic illness characterized by gross inflammation in the gastrointestinal tract that can result in symptoms such as abdominal pain, cramping, diarrhea, and bloody stools. IBD is believed to be influenced by psychological factors such as stress and anxiety. Therefore, a yoga intervention that reduces stress and anxiety may be an effective complementary treatment for these disorders. MATERIAL AND METHODS: A total of 100 IBD patients [ulcerative colitis (UC) n = 60 and Crohn's disease (CD) n = 40] during the clinical remission phase of disease were included in the study. These patients were allocated randomly to either the yoga group that underwent an 8 week yoga intervention (physical postures, pranayama, and meditation) 1- hour/day in addition to standard medical therapy (UC, n = 30; CD, n = 20) or the control group (UC, n = 30; CD n = 20), which continued with standard medical therapy alone. The main outcome measures were cardiovascular autonomic functions, serum eosinophilic cationic protein, interleukin- 2 soluble receptors, Speilberger's State Trait Anxiety Inventory (STAI) scores, and clinical symptoms. RESULTS: Before the intervention, all the outcome measures were comparable in the two groups. After the 8-week yoga intervention, fewer UC patients reported arthralgia. The number of patients reporting intestinal colic pain in the control group was higher. State and trait anxiety levels were significantly reduced in patients with UC. However, no significant changes were observed in cardiovascular autonomic functions, eosinophilic cationic proteins, or interleukin-2 soluble receptors. CONCLUSIONS: A simplified yoga-based regimen is a safe and effective complementary clinical treatment modality for patients with inflammatory bowel disease during the clinical remission phase. PMID- 26667294 TI - The Africa Yoga Project: A Participant-Driven Concept Map of Kenyan Teachers' Reported Experiences. AB - OBJECTIVE: The Africa Yoga Project (AYP) trains and funds Kenyans to teach community yoga classes. Preliminary research with a small sample of AYP teachers suggested the program had a positive impact. This study used concept mapping to explore the experiences of a larger sample. METHODS: Participants brainstormed statements about how practicing and/or teaching yoga changed them. They sorted statements into self-defined piles and rated them in terms of perceived importance. Multidimensional scaling (MDS) of sort data calculated statement coordinates wherein each statement is placed in proximity to other statements as a function of how frequently statements are sorted together by participants. These results are then and mapped in a two-dimensional space. Hierarchical cluster analysis (HCA) of these data identified clusters (i.e., concepts) among statements. Cluster average importance ratings gave the concept map depth and indicated concept importance. Bridging analysis and researchers' conceptual understanding of yoga literature facilitated HCA interpretive decisions. RESULTS: Of 72 AYP teachers, 52 and 48 teachers participated in brainstorming and sorting/rating activities, respectively. Teachers brainstormed 93 statements about how they had changed. The resultant MDS statement map had adequate validity (stress value = .29). HCA created a 12-cluster solution with the following concepts of perceived change: Identity as a Yoga Teacher; Prosocial Development; Existential Possibility; Genuine Positive Regard; Value and Respect for Others (highest importance); Presence, Acceptance, and Competence; Service and Trust; Non-judgment and Emotion Regulation (lowest importance); Engagement and Connection; Interpersonal Effectiveness; Psychosocial Functioning; and Physical Competence and Security. CONCLUSIONS: Teachers perceived the AYP as facilitating change across physical, mental, and spiritual domains. Additional research is needed to quantify and compare this change to other health promotion program outcomes. PMID- 26667295 TI - An Individualized Yoga Programme for Multiple Sclerosis: A Case Study. AB - PURPOSE: Despite the evidence that yoga is beneficial for people with multiple sclerosis (MS), substantial in-depth qualitative studies of yoga and MS-and individualized yoga programmes (IYP), in particular-are lacking. The aims of this paper are (a) to conduct a case study on an IYP for one participant with MS in terms of her experience of yoga and how yoga affected her particular symptoms of MS, and (b) to better understand the unique and changing needs of someone with MS in the context of an IYP. DESIGN AND METHOD: Data collected for this study were sourced from a qualitative case study design with data collected via a participant diary completed over the 24-week duration of an IYP; an exit interview after the final IYP session; and weekly records completed by the yoga teacher. Data were analysed using thematic analysis. FINDINGS: Over the course of the IYP, the female participant experienced an increased awareness of negative thoughts and feelings about MS and how it affected her and her body. As the programme progressed, she began to work through these feelings and, by the end of the programme, reported experiencing improvements in muscle tone, strength, balance, psychological wellbeing, and confidence. CONCLUSION: Our findings highlight the importance of a programme individualized to meet the complex health and psychological needs of individuals with MS. PMID- 26667296 TI - Feasibility of Establishing a Comprehensive Yoga Program and its Dose-Effect Relationship on Cardiovascular Risk Factors and Wellness Parameters: A Pilot Study. AB - BACKGROUND: We sought to study the feasibility of establishing a comprehensive, mostly self-directed yoga program in a hospital and its dose-effect relationship on cardiovascular risk factors and quality of life (QoL) measures over six months. METHODS: Yoga-based techniques (Advanced Yoga Practices; AYP; advancedyogapractices.com) were taught in 12 biweekly group sessions and self directed practice at home was emphasized. Cardiovascular risk factors were elucidated by interview and review of medical history. Quality of life (QoL) outcomes included the SF-36, the Cohen Perceived Stress Scale (CPSS), and the Hospital Anxiety and Depression Scale (HADS). Risk factors and QoL measures were compared in participants at baseline and six months, as well as between those practicing >= 7 times versus < 7 times per week. RESULTS: A total of 22 individuals (19 women, mean age 59 +/- 8.7 years) completed the study. At six months, changes were noted in the Mental Component Scale (MCS) of the SF-36 (p=0.0004) and the CPSS (p = 0.022). A greater improvement in CPSS was noted in those practicing >= 7 times versus < 7 times a week (p=0.045). No changes were noted in cardiovascular risk factors. CONCLUSIONS: The prescription of a self directed yoga program was feasible in a hospital setting and resulted in improvement in QoL measures at six months. Practicing more than seven times per week correlated with greater improvement in the perception of stress. Thus, at least a once-daily dose of AYP techniques for a significant improvement in perceived stress is an appropriate dose to employ and study in hospital settings. PMID- 26667297 TI - Yoga Influences Recovery During Inpatient Rehabilitation: A Pilot Study. AB - PURPOSE: The purpose of this study was to add yoga therapy to inpatient rehabilitation and assess whether patients chose to engage in yoga therapy in addition to other daily therapies, to describe patients' perceptions of how yoga therapy influenced recovery, and to assess and describe patient satisfaction with the program. METHODS: This was a single-arm pilot study, adding yoga therapy to ongoing inpatient rehabilitation. Yoga therapy was offered as group yoga or individual yoga twice a week. Semi-structured interview questions were completed via telephone post-discharge. RESULTS: A total of 55 of the 77 (71%) people contacted about the study engaged in yoga therapy in the inpatient rehabilitation setting for this study and 31 (56%) of these completed the semi-structured interview questions. Qualitative data support that participants perceived that yoga therapy improved breathing, relaxation, and psychological wellbeing. Overall, participants were satisfied with the program, although they often indicated they would like increased flexibility or frequency of yoga. Almost all participants (97%) said they would recommend the yoga therapy program to others in inpatient rehabilitation. CONCLUSION: We were able to add yoga therapy to ongoing inpatient rehabilitation and participants perceived benefits of having the yoga therapy in their rehabilitation stay. PMID- 26667298 TI - Circulating resistin is a significant predictor of mortality independently from cardiovascular comorbidities in elderly, non-diabetic subjects with chronic kidney disease. AB - CONTEXT: Resistin is associated with inflammation, atherosclerosis and cardiovascular (CV) disease. OBJECTIVE: To associate circulating resistin with all-cause and CV mortality in chronic kidney disease (CKD) patients. METHODS: Serum resistin was determined in a cohort of 80 elderly, non-diabetic patients with stable CKD at different stages in a follow-up period of 5 years. RESULTS: Circulating resistin was significantly elevated in deceased compared to alive patients. Resistin emerged as an independent biomarker of all-cause and CV mortality after a 5-year follow-up period. CONCLUSION: Elevated circulating resistin was a significant independent predictor of CV and all-cause mortality in elderly, non-diabetic CKD patients. PMID- 26667299 TI - The Disappearance of a Renaissance Man: Paolo Bianco. PMID- 26667300 TI - Unprecedented Borane, Diborane(3), Diborene, and Borylene Ligands via Pt-Mediated Borane Dehydrogenation. AB - Reactions of an aryldihydroborane with a Pt(0) complex lead to a range of novel products, including complexes with bridging diborene and diborane(3) ligands and a complex with both borylene and borane (M -> B) ligands. The products imply varying degrees of dehydrogenation of the boron centers with concomitant formation of boron-boron bonds, which in one case is later broken. These reactions show that although the dehydrocoupling of dihydroboranes is not a straightforward process in this case, the reactions are capable of connecting boron atoms in unusual ways, leading to unprecedented bonding motifs. PMID- 26667301 TI - Should we fear tubing adsorption of antibacterial drugs in extracorporeal membrane oxygenation? An answer for cephalosporins and carbapenems. PMID- 26667303 TI - Nonlinear Behavior of Gelatin Networks Reveals a Hierarchical Structure. AB - We investigate the strain hardening behavior of various gelatin networks-namely physical gelatin gel, chemically cross-linked gelatin gel, and a hybrid gel made of a combination of the former two-under large shear deformations using the pre stress, strain ramp, and large amplitude oscillations shear protocols. Further, the internal structures of physical gelatin gels and chemically cross-linked gelatin gels were characterized by small angle neutron scattering (SANS) to enable their internal structures to be correlated with their nonlinear rheology. The Kratky plots of SANS data demonstrate the presence of small cross-linked aggregates within the chemically cross-linked network whereas, in the physical gelatin gels, a relatively homogeneous structure is observed. Through model fitting to the scattering data, we were able to obtain structural parameters, such as the correlation length (xi), the cross-sectional polymer chain radius (R(c)) and the fractal dimension (d(f)) of the gel networks. The fractal dimension d(f) obtained from the SANS data of the physical and chemically cross linked gels is 1.31 and 1.53, respectively. These values are in excellent agreement with the ones obtained from a generalized nonlinear elastic theory that has been used to fit the stress-strain curves. The chemical cross-linking that generates coils and aggregates hinders the free stretching of the triple helix bundles in the physical gels. PMID- 26667302 TI - Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells. AB - The AXL receptor tyrosine kinase is frequently overexpressed in cancers and is important in cancer invasion/metastasis and chemoresistance. Here, we demonstrate a regulatory feedback loop between AXL and microRNA (miRNA) at the post transcriptional level. Both the GAS6-binding domain and the kinase domain of AXL, particularly the Y779 tyrosine phosphorylation site, are shown to be crucial for this autoregulation. To clarify the role of miRNAs in this regulation loop, approaches using bioinformatics and molecular techniques were applied, revealing that miR-34a may target the 3' UTR of AXL mRNA to inhibit AXL expression. Interestingly and importantly, AXL overexpression may induce miR-34a expression by activating the transcription factor ELK1 via the JNK signaling pathway. In addition, ectopic overexpression of ELK1 promotes apoptosis through, in part, down-regulation of AXL. Therefore, we propose that AXL is autoregulated by miR 34a in a feedback loop; this may provide a novel opportunity for developing AXL targeted anticancer therapies. PMID- 26667304 TI - No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis. AB - BACKGROUND: IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population. METHODS: In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR. RESULTS: There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4%) and in rheumatoid factor negative polyarthritis (30.5%) and a lower pro1.1 genotype in persistent oligoarthritis (20.7%) and in enthesitis-related arthritis (17%). Likelihood of the occurrence of genotype IL12 p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95% 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95% 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant. CONCLUSION: A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL 12p40 in the different subtypes of JIA. PMID- 26667306 TI - The Role of the Hostile-World Scenario in Predicting Physical and Mental Health Outcomes in Older Adults. AB - OBJECTIVE: The hostile-world scenario (HWS) denotes a personal belief system regarding threats to one's physical and mental integrity. We examined whether the HWS predicted health among older adults. METHOD: The Israeli branch of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) provided data on 1,286 participants, aged 50+, interviewed in two waves 4 years apart. A special measure assembled items pertinent to the HWS throughout the SHARE survey. Nine outcomes indicated physical health (e.g., activities of daily living, medical conditions) and mental health (e.g., depressive symptoms, satisfaction with life). RESULTS: The HWS at Wave 1 predicted all physical and mental outcomes at Wave 2, except cognitive functioning, beyond effects of sociodemographics and the respective outcome's baseline at Wave 1. This predictive effect was stronger among older participants. DISCUSSION: The results support the conception of the HWS as a psychological monitor that senses approaching functional declines in later life. PMID- 26667305 TI - Ashwagandha attenuates TNF-alpha- and LPS-induced NF-kappaB activation and CCL2 and CCL5 gene expression in NRK-52E cells. AB - BACKGROUND: The aging kidney is marked by a chronic inflammation, which may exacerbate the progression of renal dysfunction, as well as increase the susceptibility to acute injury. The identification of strategies to alleviate inflammation may have translational impact to attenuate kidney disease. METHODS: We tested the potential of ashwaganda, sutherlandia and elderberry on tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) induced chemokine (CCL2 and CCL5) expression in vitro. RESULTS: Elderberry water-soluble extract (WSE) was pro-inflammatory, while sutherlandia WSE only partially attenuated the TNF-alpha-induced changes in CCL5. However, ashwaganda WSE completely prevented TNF-alpha-induced increases in CCL5, while attenuating the increase in CCL2 expression and NF-kappaB activation. The same pattern of ashwagandha protection was seen using LPS as the pro-inflammatory stimuli. CONCLUSIONS: Taken together, these results demonstrate the ashwaganda WSE as a valid candidate for evaluation of therapeutic potential for the treatment of chronic renal dysfunction. PMID- 26667307 TI - Novel Compound Heterozygous CBS Mutations Cause Homocystinuria in a Han Chinese Family. AB - The cystathionine beta-synthase (CBS) gene has been shown to be related to homocystinuria. This study was aimed to detect the mutations in CBS in a Han Chinese family with homocystinuria. A four-generation family from Shandong Province of China was recruited in this study. All available members of the family underwent comprehensive medical examinations. Genomic DNA was collected from peripheral blood of all the participants. The coding sequence of CBS was amplified by polymerase chain reaction (PCR), followed by direct DNA sequencing. Among all the family members, three affected individuals showed typical clinical features of homocystinuria. Two novel compound heterozygous mutations in the CBS gene, c.407T > C (p. L136P) and c.473C > T (p.A158V), were identified by sequencing analysis in this family. Both of the two missense mutations were detected in the three patients. Other available normal individuals, including the patients' parents, grand parents, her younger sister and brother in this family either carried one of the two mutations, or none. In addition, the two mutations were not found in 600 ethnically matched normal controls. This study provides a mutation spectrum of CBS resulting in homocystinuriain a Chinese population, which may shed light on the molecular pathogenesis and clinical diagnosis of CBS associated homocystinuria. PMID- 26667308 TI - Prevalence and Characteristics of Pre-Operative Delirium in Hip Fracture Patients. AB - BACKGROUND: Delirium is a common complication of hip fracture and is associated with negative outcomes. Previous studies document risk factors for post-operative delirium but have frequently excluded patients with pre-operative delirium. OBJECTIVE: This study endeavours to document prevalence and risk factors for pre operative delirium in hip fracture patients and compares risk factor profiles and outcomes between pre- and post-operative delirium. METHODS: 283 hip fracture patients were assessed pre-operatively with the Delirium Elderly At Risk (DEAR) instrument, Mini-Mental State Examination (MMSE), and Confusion Assessment Method (CAM). They were followed on post-operative days 1, 3, and 5 for the presence of delirium. Doses of opioids were recorded. Wait time to surgery, length of stay, and discharge site were noted. RESULTS: Delirium was present in 57.6% patients pre-operatively and 41.7% post-surgery. Not all patients (62%) with pre-operative delirium also had post-operative delirium. There was a considerable overlap in risk factors, with some differences. Wait time to surgery, number of comorbidities, and total pre-operative opioid and lorazepam doses were associated with pre- but not post-operative delirium. Negative outcomes were more closely associated with post-operative delirium. CONCLUSION: Delirium is common in pre hip fracture surgery patients, and not all patients with pre-operative delirium go on to have post-operative delirium. Risk factor profiles are not identical, raising the possibility of identifying and intervening in patients at high risk of delirium pre-operatively. PMID- 26667309 TI - Recent advances in vaccine delivery. AB - The field of vaccination is moving from the use of attenuated or inactivated pathogens to safer but less immunogenic protein and peptide antigens, which require stronger adjuvant compositions. Antigen delivery carriers appear to play an important role in vaccine development, providing not only antigen protection and controlled release but also an intrinsic adjuvant potential. Among them, carriers based on polymers and lipids are the most representative ones. Patent applications in this area have disclosed, either the design and preparation methods for new biocompatible antigen delivery systems or the application of the previously developed systems for the delivery of novel antigens. Some of them have also reported the use of these technologies for modern therapeutic vaccination approaches. PMID- 26667310 TI - Interventions that support the creation of dementia friendly environments in health care: protocol for a realist review. AB - BACKGROUND: Improving health-care outcomes for people living with dementia when they are admitted to hospital is a policy priority. Dementia friendly interventions in health care promote inclusion of patients and carers in decision making and adapt practices and environments to be appropriate to the needs of people with cognitive impairment. While there has been a wealth of activity, the number of studies evaluating interventions is limited, and the majority focuses on reporting staff and organisational outcomes. By focusing on patient and carer outcomes, this review will aim to develop an explanatory account of how and in what circumstances dementia friendly environments in health care work for people living with dementia and with what outcomes. METHOD/DESIGN: Realist review is a theory-driven method which seeks to produce explanatory accounts of why interventions work and specifically, what combination of components are most effective in producing particular outcomes. Stakeholder interviews, a review of the literature, and an expert steering group workshop will be used to explore the assumptions behind interventions that are designed to enhance health care for people living with dementia to understand the underlying programme theories. The review will focus on studies that report patient and carer outcomes, including involvement in decision-making, length of stay and referral to long-term care, adverse incidents (e.g. patient distress, delirium falls, nutrition and hydration and infection), antipsychotic medication prescribing, evidence of patient-centred care and patient and carer satisfaction. DISCUSSION: The review will provide an explanatory model about how dementia friendly interventions in hospital settings improve outcomes for people living with dementia and their family carers and in what circumstances for future testing and evaluation of future dementia friendly initiatives. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017562. PMID- 26667311 TI - Correlation between personality type and vocal pathology: A nonrandomized case control study. AB - OBJECTIVES/HYPOTHESIS: In this study we have made an attempt to find out if there is any correlation with type of personality (type A or B) and incidence of vocal pathology, subsequent to a tendency of vocal abuse. We also noted the loudness of speech and rate of speech for both personality types and compared these parameters for each personality type. STUDY DESIGN: A total of 100 subjects (50 with vocal pathologies and 50 with normal vocal folds) underwent voice and personality assessment, and the above-mentioned factors were compared with statistical methods. RESULTS: It was found that subjects with type A personality had a statistically significant increased incidence of vocal pathology, as compared to those with type B personality (P = .04). The other two parameters (i.e., loudness of speech and rate of speech) were both found to be higher in subjects with type A personality than those with type B, but did not attain statistical significance. CONCLUSIONS: This study shows that there is a very close relationship between personality type and voice quality, and the incidence of vocal abuse and subsequent vocal pathologies are heavily governed by the person's personality traits. LEVEL OF EVIDENCE: 3b Laryngoscope, 126:2063-2066, 2016. PMID- 26667312 TI - Cortisol response to an induction of negative affect among adolescents with and without loss of control eating. AB - BACKGROUND: Adults with binge eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge eating disorder. METHODS: We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at -80, 0, 30 and 50 min relative to film administration, and state mood ratings were reported before and after the film. RESULTS: Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps > 0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps > 0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps > 0.05). CONCLUSIONS: A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations. PMID- 26667313 TI - Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women. AB - OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3 35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD. PMID- 26667314 TI - Systemic sclerosis and calcinosis cutis: response to rituximab. AB - WHAT IS KNOWN AND OBJECTIVE: Calcinosis cutis (or cutaneous calcification) is a type of calcinosis wherein calcium deposits form in the skin and frequently encountered in limited cutaneous subtype of disease. So far, no treatment has shown an explicit beneficial effect. Medical therapy for calcinosis cutis with rituximab is limited and of variable benefit. CASE SUMMARY: Our patient was 54 year-old lady, a case of limited cutaneous scleroderma with widespread progressive calcinosis cutis unresponsive to current therapy. She went under treatment with rituximab with no successful outcome. WHAT IS NEW AND CONCLUSION: Results of therapy with rituximab on regression/improvement of systemic sclerosis related calcinosis are limited and non-conclusive. PMID- 26667315 TI - Frequent Malaria Drives Progressive Vdelta2 T-Cell Loss, Dysfunction, and CD16 Up regulation During Early Childhood. AB - gammadelta T cells expressing Vdelta2 may be instrumental in the control of malaria, because they inhibit the replication of blood-stage parasites in vitro and expand during acute malaria infection. However, Vdelta2 T-cell frequencies and function are lower among children with heavy prior malaria exposure. It remains unclear whether malaria itself is driving this loss. Here we measure Vdelta2 T-cell frequency, cytokine production, and degranulation longitudinally in Ugandan children enrolled in a malaria chemoprevention trial from 6 to 36 months of age. We observed a progressive attenuation of the Vdelta2 response only among children incurring high rates of malaria. Unresponsive Vdelta2 T cells were marked by expression of CD16, which was elevated in the setting of high malaria transmission. Moreover, chemoprevention during early childhood prevented the development of dysfunctional Vdelta2 T cells. These observations provide insight into the role of Vdelta2 T cells in the immune response to chronic malaria. PMID- 26667316 TI - Microscopic Plasmodium falciparum Gametocytemia and Infectivity to Mosquitoes in Cambodia. AB - Although gametocytes are essential for malaria transmission, in Africa many falciparum-infected persons without smear-detectable gametocytes still infect mosquitoes. To see whether the same is true in Southeast Asia, we determined the infectiousness of 119 falciparum-infected Cambodian adults to Anopheles dirus mosquitoes by membrane feeding. Just 5.9% of subjects infected mosquitoes. The 8.4% of patients with smear-detectable gametocytes were >20 times more likely to infect mosquitoes than those without and were the source of 96% of all mosquito infections. In low-transmission settings, targeting transmission-blocking interventions to those with microscopic gametocytemia may have an outsized effect on malaria control and elimination. PMID- 26667318 TI - Shared decision-making for the elderly patient with a surgical condition. PMID- 26667319 TI - Anthropometric factors, adult weight gain, and mammographic features. AB - PURPOSE: To evaluate the association between anthropometric factors, weight gain during adulthood, and mammographic features among 1,435 women recruited at screening mammography. METHODS: Spearman's partial coefficients were used to evaluate the correlation of anthropometric factors with mammographic features (percent density, absolute dense area, and non-dense area). Multivariate generalized linear models were used to evaluate the associations between weight change categories and mammographic features. RESULTS: Body mass index was inversely correlated with percent density (r = -0.49, p < 0.0001) or absolute dense area (r = -0.21, p < 0.0001) and positively correlated with absolute non dense area (r = 0.69, p < 0.0001). However, body mass index was positively correlated with absolute dense area when adjusting for absolute non-dense area (r = 0.16, p < 0.0001). Similar results were observed for weight, waist circumference, and waist-to-hip ratio with mammographic features. Within increasing categories of weight change, percent density (p trend < 0.0001) and absolute dense area (p trend = 0.025) increased, while absolute non-dense area decreased (p trend < 0.0001). After stratification by the median of non-dense area, the positive association between weight gain and absolute dense area remained only among women with higher non-dense area. CONCLUSIONS: Adiposity seems positively associated with both dense and non-dense areas following adjustment for each other. Our findings suggest a higher breast dense area among women who gained weight and that a minimum of breast fat may be needed to promote the proliferation of this fibroglandular tissue. PMID- 26667321 TI - Localized one-dimensional single voxel magnetic resonance spectroscopy without J coupling modulations. AB - PURPOSE: To acquire single voxel localized one-dimensional 1 H magnetic resonance spectroscopy (MRS) without J coupling modulations, free from amplitude and phase distortions. METHODS: A pulse sequence, named PRESSIR, is developed for volume localized MRS without J modulations at arbitrary echo time (TE). The J coupling evolution is suppressed by the J-refocused module that uses a 90 degrees pulse at the midpoint of a double spin echo. RESULTS: The localization performance of the PRESSIR sequence was tested with a two-compartment phantom. The proposed sequence shows similar voxel localization accuracy as PRESS. Both PRESSIR and PRESS sequences were performed on MRS brain phantom and pig brain tissue. PRESS spectra suffer from amplitude and phase distortions due to J modulations, especially under moderate and long TEs, while PRESSIR spectra are almost free from distortions. CONCLUSION: The PRESSIR sequence proposed herein enables the acquisition of single voxel in-phase MRS within a single scan. It allows an enhanced signal intensity of J coupling metabolites and reducing undesired broad resonances with short T2s while suppressing J modulations. Moreover, it provides an approach for direct measurement of nonoverlapping J coupling peaks and of transverse relaxation times T2s. Magn Reson Med 76:1661-1667, 2016. (c) 2015 International Society for Magnetic Resonance in Medicine. PMID- 26667322 TI - Aliphatic amidase of Rhodococcus rhodochrous PA-34: Purification, characterization and application in synthesis of acrylic acid. AB - An intracellular aliphatic amide degrading inducible amidase produced by Rhodococcus rhodochrous PA-34 was characterized and acrylic acid synthesis from acrylamide was carried out using whole cell amidase. A bioprocess was developed at 50 ml fed batch reaction using 400 mM acrylamide feeding at an interval of 30 min resulted in the production of 4 g acrylic acid with volumetric and catalytic productivity of 80 g/l and 19 g/g/h respectively. The amidase of this organism had molecular weight of 40 kDa and was purified to 8.5 fold with 8% yield. This enzyme was active within the temperature range of 30 to 60 degrees C, with optimum temperature 45 degrees C and pH 7.5. The Vmax, Km, and kcat of purified amidase were calculated as 250 U/mg protein, 4.5 mM, and 166 sec-1 for acrylamide. The enzyme showed tolerance to metal chelating agent (EDTA) and was strongly inhibited by heavy metal ions Hg2+, Ag2+, Cu2+ and Co2+. R. rhodochrous PA-34 amidase preferentially hydrolyzed small aliphatic toxic amide such as acrylamide. Thus, the amidase of R. rhodochrous PA-34 is promising biocatalyst for the synthesis of industrially important acids and biodegradation of toxic amides. PMID- 26667320 TI - Use of exogenous hormones and the risk of breast cancer: results from self reported survey data with validity assessment. AB - PURPOSE: Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data. METHODS: The survey 'Women's Health and Use of Hormones' was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys. RESULTS: We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10-1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (>=2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12-1.68) for premenopausal and 1.11 (95 % CI 1.03-1.20) for postmenopausal women, when compared to never-users of other HC. CONCLUSIONS: Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant. PMID- 26667317 TI - Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside. AB - Recent advances in basic cardiovascular research as well as their translation into the clinical situation were the focus at the last "New Frontiers in Cardiovascular Research meeting". Major topics included the characterization of new targets and procedures in cardioprotection, deciphering new players and inflammatory mechanisms in ischemic heart disease as well as uncovering microRNAs and other biomarkers as versatile and possibly causal factors in cardiovascular pathogenesis. Although a number of pathological situations such as ischemia reperfusion injury or atherosclerosis can be simulated and manipulated in diverse animal models, also to challenge new drugs for intervention, patient studies are the ultimate litmus test to obtain unequivocal information about the validity of biomedical concepts and their application in the clinics. Thus, the open and bidirectional exchange between bench and bedside is crucial to advance the field of ischemic heart disease with a particular emphasis of understanding long lasting approaches in cardioprotection. PMID- 26667323 TI - Formation Dynamics of CH3NH3PbI3 Perovskite Following Two-Step Layer Deposition. AB - Hybrid metal-halide perovskites have emerged as a leading class of semiconductors for optoelectronic devices because of their desirable material properties and versatile fabrication methods. However, little is known about the chemical transformations that occur in the initial stages of perovskite crystal formation. Here we follow the real-time formation dynamics of MAPbI3 from a bilayer of lead iodide (PbI2) and methylammonium iodide (MAI) deposited through a two-step thermal evaporation process. By lowering the substrate temperature during deposition, we are able to initially inhibit intermixing of the two layers. We subsequently use infrared and visible light transmission, X-ray diffraction, and photoluminescence lifetime measurements to reveal the room-temperature transformations that occur in vacuum and ambient air, as MAI diffuses into the PbI2 lattice to form MAPbI3. In vacuum, the transformation to MAPbI3 is incomplete as unreacted MAI is retained in the film. However, exposure to moist air allows for conversion of the unreacted MAI to MAPbI3, demonstrating that moisture is essential in making MAI more mobile and thus aiding perovskite crystallization. These dynamic processes are reflected in the observed charge carrier lifetimes, which strongly fluctuate during periods of large ion migration but steadily increase with improving crystallinity. PMID- 26667324 TI - Correlation between miR-21 expression and laryngeal carcinoma risks: a meta analysis. AB - OBJECTIVE: To evaluate the expression and clinical significance of miR-21 in the tissues of laryngeal carcinoma using meta-analysis. METHODS: Literature databases including PubMed, EMbase, The Cochrane Library, Web of Science, Google Scholar, and the British Library. Two reviewers independently identified the literature according to inclusion and exclusion criteria, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using Stata 12.0 and RevMan 5.0 software. RESULTS: A total of four studies involving 160 cases were included. No significant heterogeneity was found between studies. The results of meta-analysis showed high miR-21 expression was found in Laryngeal cancer than non-neoplasm tissue (odds ratio = 4.47, 95%CI 2.59 to 7.73, P = 0.02). Only one study reported the expression of miR-21 between TMN (tumor, metastasis, node) I to II and TMN III to IV. CONCLUSION: miR-21expression is notably correlated to laryngeal carcinoma and its clinically pathologic features. It suggests that higher miR-21 expression may be a risk factor of laryngeal carcinoma and a potential molecular biomarker. For the quantity and quality limitation of the included studies, the conclusion still needs to be further proved by performing more high-quality studies. PMID- 26667325 TI - Alcohol- and water-soluble bis(tpy)quaterthiophenes with phosphonium side groups: new conjugated units for metallo-supramolecular polymers. AB - Bis(tpy)quaterthiophenes with symmetrically distributed two and four 6-bromohexyl side groups were prepared and modified by the reaction with triethylphosphine to give the corresponding ionic species. Both ionic and non-ionic bis(tpy)quaterthiophenes (unimers) were assembled with Zn(2+) and Fe(2+) ions to conjugated metallo-supramolecular polymers (MSPs), of which the ionic ones are soluble in alcohols and those derived from tetrasubstituted unimers are soluble even in water. The differences in assembly are specified between systems with (i) ionic and non-ionic unimers, (ii) Zn(2+) and Fe(2+) ion couplers, and (iii) methanol and water solvents. A substantial decrease in the stability of Fe-MSPs and a surprisingly high red shift of the luminescence band of Zn-MSPs were observed on going from methanol to aqueous solutions. PMID- 26667326 TI - Preface. PMID- 26667327 TI - Rat models of cardiometabolic diseases: baseline clinical chemistries, and rationale for their use in examining air pollution health effects. AB - Individuals with cardiovascular and metabolic diseases (CVD) are shown to be more susceptible to adverse health effects of pollutants. Rodent models of CVD are used for examining susceptibility variations. CVD models developed by selective inbreeding are shown to represent the etiology of human disease and metabolic dysfunction. The goal of this article was to review the origin and the pathobiological features of rat models of varying CVD with or without metabolic syndrome and healthy laboratory rat strains to allow better interpretation of the data regarding their susceptibility to air pollutant exposures. Age-matched healthy Sprague-Dawley (SD), Wistar (WIS) and Wistar Kyoto (WKY), and CVD-prone spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF) and insulin-resistant JCR:LA-cp obese (JCR) rat models were considered for this study. The genetics and the underlying pathologies differ between these models. Normalized heart weights correlated with underlying cardiac disease while wide differences exist in the number of white blood cells and platelets within healthy strains and those with CVD. High plasma fibrinogen and low angiotensin converting enzyme activity in FHH might relate to kidney disease and associated hypertension. However, other obese strains with known kidney lesions do not exhibit decreases in ACE activity. The increased activated partial thromboplastin time only in SHSP correlates with their hemorrhagic stroke susceptibility. Increases plasma lipid peroxidation in JCR might reflect their susceptibility to acquire atherosclerosis. These underlying pathologies involving CVD and metabolic dysfunction are critical in interpretation of findings related to susceptibility variations of air pollution health effects. PMID- 26667328 TI - Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease. AB - To elucidate key factors of host susceptibility to air pollution, healthy and cardiovascular (CV)-compromised rats were exposed to air or ozone (O3) at 0.25, 0.5, or 1.0 ppm for 4 h. We hypothesized that rat strains with the least cardiac reserve would be most prone to develop significant health effects. Using flow whole body plethysmography (FWBP), ventilatory responses in healthy 3-month-old male rats [i.e. Wistar-Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) strains] were compared with hypertensive [i.e. spontaneously hypertensive (SH), fawn-hooded-hypertensive (FHH), and SH-stroke-prone (SHSP)] strains and obese [i.e. SH-heart failure-prone (SHHF) and JCR:LA-cp, atherosclerosis-prone (JCR)] strains. SH were slower to acclimate to the FWBP chambers. At 0-h post-air exposure, SHSP and SHHF exhibited hyperpnea, indicative of cardiopulmonary insufficiency. At 0-h-post-O3, all but one strain showed significant concentration-dependent decreases in minute volume [MV = tidal volume (TV) * breathing frequency]. Comparing air with 1.0 ppm responses, MV declined 20-27% in healthy, 21-42% in hypertensive, and 33% in JCR rats, but was unchanged in SHHF rats. Penh increased significantly in all strains, with disproportionate increases in "responder" WKY and FHH strains. By 20 h, most changes had resolved, although Penh remained elevated in WKY, SH, and SHSP. Based on the effective dose estimates (O3 ppm * h * MV), the most CV-compromised (SHSP and SHHF) strains received significantly greater O3 lung deposition (25% and 40%, respectively). Data support epidemiologic associations that individuals with cardiopulmonary insufficiency are at greater risk for urban pollutant exposure due, in part, to enhanced lung deposition and exacerbation of hypoxia and pathophysiologic processes of heart failure. PMID- 26667329 TI - Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure. AB - Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. However, cross-model organ pathologies and clinical manifestations are often not compared. We hypothesized that genetic CVD rat models will exhibit baseline pathologies and will thus express varied lung response to acute ozone exposure. Male 12-14-week old healthy Wistar Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) rats and CVD-compromised spontaneously hypertensive (SH), fawn-hooded hypertensive (FHH), stroke-prone SH (SHSP), obese SH heart-failure (SHHF), obese diabetic JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h and clinical biomarkers, and lung, heart and kidney pathologies were compared immediately following (0-h) or 20-h later. Strain differences were observed between air exposed CVD-prone and WKY rats in clinical biomarkers and in kidney and heart pathology. Serum cholesterol was higher in air-exposed obese SHHF and JCR compared to other air-exposed strains. Ozone did not produce lesions in the heart or kidney. CVD-prone and SD rats demonstrated glomerulopathy and kidney inflammation (WKY = WIS = SH < SD = SHSP < SHHF < JCR = FHH) regardless of ozone. Cardiac myofiber degeneration was evident in SH, SHHF, and JCR, while only JCR tends to have inflammation in coronaries. Lung pathology in air-exposed rats was minimal in all strains except JCR. Ozone induced variable alveolar histiocytosis and bronchiolar inflammation; JCR and SHHF were less affected. This study provides a comparative account of the clinical manifestations of disease and early-life organ pathologies in several rat models of CVD and their differential susceptibility to lung injury from air pollutant exposure. PMID- 26667330 TI - Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models. AB - The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure dependent on the type and severity of disease. Healthy male 12-14-week-old Wistar Kyoto (WKY), Wistar (WS) and Sprague Dawley (SD); and CVD-compromised spontaneously hypertensive (SH), Fawn Hooded hypertensive (FHH), stroke-prone spontaneously hypertensive (SHSP), obese spontaneously hypertensive heart failure (SHHF) and obese JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h; pulmonary injury and inflammation were analyzed immediately following (0-h) or 20-h later. Baseline bronchoalveolar lavage fluid (BALF) protein was higher in CVD strains except for FHH when compared to healthy. Ozone-induced increases in protein and inflammation were concentration-dependent within each strain but the degree of response varied from strain to strain and with time. Among healthy rats, SD were least affected. Among CVD strains, lean rats were more susceptible to protein leakage from ozone than obese rats. Ozone caused least neutrophilic inflammation in SH and SHHF while SHSP and FHH were most affected. BALF neutrophils and protein were poorly correlated when considering the entire dataset (r = 0.55). The baseline and ozone induced increases in cytokine mRNA varied markedly between strains and did not correlate with inflammation. These data illustrate that the degree of ozone induced lung injury/inflammation response is likely influenced by both genetic and physiological factors that govern the nature of cardiovascular compromise in CVD models. PMID- 26667331 TI - Strain differences in antioxidants in rat models of cardiovascular disease exposed to ozone. AB - We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to O3 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF), insulin-resistant JCR:LA-cp obese (JCR) and Fawn-Hooded hypertensive (FHH)] were compared with normal strains [Wistar, Sprague-Dawley (SD) and Wistar Kyoto (WKY)]. Total glutathione (GSH + GSSG or GSx), reduced ascorbate (AH2), uric acid (UA) and antioxidant enzymes were determined in lung, heart and BALF immediately (0 h) or 20-h post 4-h nose-only exposure to 0.0, 0.25, 0.5 and 1.0 ppm O3. Basal- and O3-induced antioxidant substances in tissues varied widely among strains. Wistar rats had a robust O3-induced increase in GSx and AH2 in the lung. Two CVD strains (JCR and SHHF) had high basal levels of AH2 and GSx in BALF as well as high basal lung UA. Across all strains, high BALF GSx was only observed when high BALF AH2 was present. CVD rats tended to respond less to O3 than normal. High-basal BALF AH2 levels were associated with decreased O3 toxicity. In summary, large differences were observed between both normal and CVD rat strains in low-molecular weight antioxidant concentrations in lung, BALF and heart tissue. Wistar (normal) and JCR and SHHF (CVD) rats appeared to stand out as peculiar in terms of basal- or O3-induced changes. Results elucidate interactions among antioxidants and air pollutants that could enhance understanding of cardiopulmonary disease. PMID- 26667332 TI - Left ventricular gene expression profile of healthy and cardiovascular compromised rat models used in air pollution studies. AB - The link between pollutant exposure and cardiovascular disease (CVD) has prompted mechanistic research with animal models of CVD. We hypothesized that the cardiac gene expression patterns of healthy and genetically compromised, CVD-prone rat models, with or without metabolic impairment, will reveal underlying disease processes that facilitate understanding of the mechanisms of air pollution susceptibility differences. Left ventricular gene expression was examined using Affymetrix rat 230A-gene arrays in male, age-matched (12-14 weeks old) healthy Wistar Kyoto (WKY) and CV-compromised spontaneously hypertensive (SH), stroke prone SH (SHSP), obese SH heart failure (SHHF) and obese insulin-resistant (JCR) rats. Principle component analysis separated strains in three clusters: (1) WKY, (2) JCR and )3) SH, SHSP and SHHF. Gene expression pattern in JCR differed from all other CVD strains. Both SHHF and JCR strains presented the most differentially expressed genes from WKY, but generally with opposing directional pattern suggesting that the CVD in these strains arise through different mechanisms. Hierarchical clustering of nuclear factor-kappaB target genes indicated varying degrees of, but similar directional changes, in SH, SHSP and SHHF relative to WKY rats, which may relate to the severity of their CVD. The JCR strain had less pronounced expressions of these genes suggesting milder cardiac disease. No unique expression pattern could be identified for genes implicated in stroke and heart failure in SHSP and SHHF rats, respectively. The data show that the CVD pathophysiological mechanisms differ in models with different genetic backgrounds, and therefore, the mechanisms by which air pollutants affect the cardiopulmonary system are likely to vary. PMID- 26667333 TI - Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats. AB - Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive analysis of these changes will allow us to better understand the mechanism of pulmonary injury and inflammation. Male Wistar Kyoto rats (10-12 week) were exposed to air, or ozone (0.25, 0.5 or 1.0 ppm) for 4 h and pulmonary injury and inflammation were assessed at 0-h or 20 h (n = 8/group). Lung gene expression profiling was assessed at 0-h (air and 1.0 ppm ozone, n = 3-4/group). At 20-h bronchoalveolar lavage, fluid protein and neutrophils increased at 1 ppm ozone. Numerous genes involved in acute inflammatory response were up-regulated along with changes in genes involved in cell adhesion and migration, steroid metabolism, apoptosis, cell cycle control and cell growth. A number of NRF2 target genes were also induced after ozone exposure. Based on expression changes, Rela, SP1 and TP3-mediated signaling were identified to be mediating downstream changes. Remarkable changes in the processes of endocytosis provide the insight that ozone-induced lung injury and inflammation are likely initiated by changes in cell membrane components and receptors likely from oxidatively modified lung lining lipids and proteins. In conclusion, ozone-induced injury and inflammation are preceded by changes in gene targets for cell adhesion/migration, apoptosis, cell cycle control and growth regulated by Rela, SP1 and TP53, likely mediated by the process of endocytosis and altered steroid receptor signaling. PMID- 26667334 TI - Pulmonary transcriptional response to ozone in healthy and cardiovascular compromised rat models. AB - The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD prone rat models will provide mechanistic insights into susceptibility differences to ozone. The lung expression profiles of healthy Wistar Kyoto (WKY) and CVD-compromised spontaneously hypertensive (SH), stroke-prone SH (SHSP), obese SH heart failure (SHHF) and obese, atherosclerosis-prone JCR rats were analyzed using Affymetrix platform immediately after 4-h air or 1 ppm ozone exposure. At baseline, the JCR exhibited the largest difference in the number of genes among all strains when compared with WKY. Interestingly, the number of genes affected by ozone was inversely correlated with genes different at baseline relative to WKY. A cluster of NFkB target genes involved in cell-adhesion, antioxidant response, inflammation and apoptosis was induced in all strains, albeit at different levels (JCR < WKY < SHHF < SH < SHSP). The lung metabolic syndrome gene cluster indicated expressions in opposite directions for SHHF and JCR suggesting different mechanisms for common disease phenotype and perhaps obesity-independent contribution to exacerbated lung disease. The differences in expression of adrenergic receptors and ion-channel genes suggested distinct mechanisms by which ozone might induce protein leakage in CVD models, especially SHHF and JCR. Thus, the pulmonary response to ozone in CVD strains was likely linked to the defining gene expression profiles. Differential transcriptional patterns between healthy and CVD rat strains at baseline, and after ozone suggests that lung inflammation and injury might be influenced by multiple biological pathways affecting inflammation gene signatures. PMID- 26667335 TI - Executive Summary: variation in susceptibility to ozone-induced health effects in rodent models of cardiometabolic disease. AB - Seven million premature deaths occur annually due to air pollution worldwide, of which ~80% are attributed to exacerbation of cardiovascular disease (CVD), necessitating greater attention to understanding the causes of susceptibility to air pollution in this sector of population. We used rat models of CVD with or without obesity and compared them to healthy strains to examine the risk factors of ozone-induced lung injury and inflammation. We examined functional, biochemical and molecular changes in several organs to evaluate how physiological factors as well as compensatory antioxidant reserves modulate processes by which ozone injury is influenced by underlying disease. In this study, we highlight key findings of this series of reports. We show that underlying cardiopulmonary insufficiency in genetically predisposed rats appears to increase the effective ozone dose; thus dosimetry is one factor contributing to exacerbated ozone effects. We further show that antioxidant reserve in airway lining fluid modulates ozone-induced damage such that strains with the least antioxidant reserve incur the greatest injury. And finally, we show that the inflammatory response to ozone is governed by a cluster of genes involved in regulating cytokine release, trafficking of inflammatory cells and processes related to cellular apoptosis and growth. All such processes are influenced not only by ozone dosimetry and the lung antioxidant milieu but also by the strain-specific genetic factors. In using a comprehensive systems biology research approach, our data reveal key risk factors for--and strategies to reduce risk of--air pollution mortality among those with CVD. PMID- 26667336 TI - Lung Cancer Statistics. AB - Lung cancer is the leading cause of cancer death among both men and women in the United States. It is also the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide. Lung cancer rates and trends vary substantially by sex, age, race/ethnicity, socioeconomic status, and geography because of differences in historical smoking patterns. Lung cancer mortality rates in the United States are highest among males, blacks, people of lower socioeconomic status, and in the mid-South (e.g., Kentucky, Mississippi, Arkansas, and Tennessee). Globally, rates are highest in countries where smoking uptake began earliest, such as those in North America and Europe. Although rates are now decreasing in most of these countries (e.g., United States, United Kingdom, Australia), especially in men, they are increasing in countries where smoking uptake occurred later. Low- and middle-income countries now account for more than 50% of lung cancer deaths each year. This chapter reviews lung cancer incidence and mortality patterns in the United States and globally. PMID- 26667337 TI - Epidemiology of Lung Cancer. AB - Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines. PMID- 26667338 TI - Lung Cancer in Never Smokers. AB - Lung cancer is predominantly associated with cigarette smoking; however, a substantial minority of patients with the disease have never smoked. In the US it is estimated there are 17,000-26,000 annual deaths from lung cancer in never smokers, which as a separate entity would be the seventh leading cause of cancer mortality. Controversy surrounds the question of whether or not the incidence of lung cancer in never-smokers is increasing, with more data to support this observation in Asia. There are several factors associated with an increased risk of developing lung cancer in never smokers including second hand smoke, indoor air pollution, occupational exposures, and genetic susceptibility among others. Adenocarcinoma is the most common histology of lung cancer in never smokers and in comparison to lung cancer in smokers appears less complex with a higher likelihood to have targetable driver mutations. PMID- 26667339 TI - Immune Therapy. AB - Lung cancer has long been considered an unsuitable target for immunotherapy due to its proposed immunoresistant properties. However, recent evidence has shown that anti-tumor immune responses can occur in lung cancer patients, paving the way for lung cancer as a novel target for immunotherapy. In order to take full advantage of the potential of immunotherapy, research is focusing on the presence and function of various immunological cell types in the tumor microenvironment. Immune cells which facilitate or inhibit antitumor responses have been identified and their prognostic value in lung cancer has been established. Knowledge regarding these pro- and anti-tumor immune cells and their mechanisms of action has facilitated the identification of numerous potential immunotherapeutic strategies and opportunities for intervention. A plethora of immunotherapeutic approaches is currently being developed and studied in lung cancer patients and phase 3 clinical trials are ongoing. Many different immunotherapies have shown promising clinical effects in patients with limited and advanced stage lung cancer, however, future years will have to tell whether immunotherapy will earn its place in the standard treatment of lung cancer. PMID- 26667340 TI - Anti-angiogenesis in Personalized Therapy of Lung Cancer. AB - Upregulation of angiogenesis is a frequent occurrence in lung cancer and is reported to represent a negative prognostic factor. This provides a rationale for the development and evaluation of anti-angiogenic agents. To date bevacizumab, a monoclonal antibody directed against serum VEGF, is the only anti-angiogenic agent that has demonstrated improved overall survival for patients with lung cancer. Meta-analysis of trials of bevacizumab in combination with platinum-based chemotherapy for NSCLC, show a 10% reduction in the risk of death (HR 0.90, 95% CI 0.81-0.99). However, therapy with bevacizumab is limited to NSCLC patients with non-squamous histology, good performance status, no brain metastases and the absence of bleeding or thrombotic disorders. More recently, similar survival was observed in a non bevacizumab containing regimen of carboplatin, pemetrexed and maintenance pemetrexed. Multiple oral anti-angiogenic compounds have been evaluated in NSCLC, both in first-line therapy, or upon disease progression. The majority of agents have shown some evidence of activity, but none have clearly demonstrated improvements in overall survival. Increased toxicities have been observed, including an increased risk of death for some agents, limiting their development. Promising data exist for sunitinib in patients with heavily pre treated NSCLC, and nintedanib in combination with docetaxel, as second-line therapy for NSCLC. However, these findings require validation. Currently, there is no established role for anti-angiogenic therapy in SCLC, although there is some promise for sunitinib as maintenance therapy following platinum and etoposide chemotherapy. The challenge for anti-angiogenic therapy is to understand whether treatment effects in a subpopulation, are lost among a larger unselected population of patients. There is a need for additional translational research to identify predictive biomarkers for anti-angiogenic therapy. PMID- 26667341 TI - Target Therapy in Lung Cancer. AB - Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way. PMID- 26667342 TI - Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors and Therapeutic Approaches: An Update. AB - Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non small cell lung cancer (NSCLC) is mediated by two major mechanisms namely secondary mutation T790M in EGFR and cMET amplification. Other molecular mediators which contribute towards TKI resistance include the activation of compensatory growth signaling, epithelial mesenchymal transition and microRNAs regulating EGFR and cMET levels. In this chapter, we have included the major mechanisms which contribute towards EGFR TKI resistance in NSCLC. Several therapeutic approaches to overcome TKI resistance are also presented which include second and third generation EGFR TKI inhibitors and cMET inhibitors. Further, the rationale to utilize the combination therapies to simultaneously target EGFR and other major oncogene addictive pathway such as ERBB2 and AXL kinase is outlined. Another promising approach to overcome TKI resistance is to potentiate EGFR protein for degradation. These studies will best be utilized when we can identify the oncogene addictions in an individual patient and tailor the therapy/therapies accordingly for the maximum benefits. PMID- 26667343 TI - KRAS-Mutant Lung Cancers in the Era of Targeted Therapy. AB - KRAS-mutant lung cancers account for approximately 25% of non-small cell lung carcinomas, thus representing an enormous burden of cancer worldwide. KRAS mutations are clear drivers of tumor growth and are characterized by a complex biology involving the interaction between mutant KRAS, various growth factor pathways, and tumor suppressor genes. While KRAS mutations are classically associated with a significant smoking history, they are also identified in a substantial proportion of never-smokers. These mutations are found largely in lung adenocarcinomas with solid growth patterns and tumor-infiltrating lymphocytes. A variety of tools are available for diagnosis including Sanger sequencing, multiplex mutational hotspot profiling, and next-generation sequencing. The prognostic and predictive roles of KRAS status remain controversial. It has become increasingly clear, however, that KRAS mutations drive primary resistance to EGFR tyrosine kinase inhibition. Until recently, mutant KRAS was not thought of as a clinically-targetable driver in lung cancers. With the expansion of our knowledge regarding the biology of KRAS-mutant lung cancers and the role of MEK and PI3K/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change. PMID- 26667344 TI - Anaplastic Lymphoma Kinase (ALK) Signaling in Lung Cancer. AB - Chromosomal rearrangement in the anaplastic lymphoma kinase (ALK) gene was identified as an oncogenic driver in non-small cell lung cancer (NSCLC) in 2007. A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al. Oncologist 17:1351-1375, 2012). Knowledge gained from treating ALK-rearranged NSCLC patients including the presenting clinicopathologic characteristics, methods of detecting ALK-rearranged NSCLC, pattern of relapse and acquired resistance mechanisms while on crizotinib, and the clinical activities of more potent ALK inhibitors has led us to a detailed and ever expanding knowledge of the ALK signaling pathway in lung cancer but also raising many more questions that remained to be answered in the future. This book chapter will provide a concise summary of the importance of ALK signaling pathway in lung cancer. Understanding the ALK signaling pathway in lung cancer will likely provide the roadmap to the management of major epithelial malignancies driven by receptor tyrosine kinase rearrangement. PMID- 26667345 TI - Chemotherapy Resistance in Lung Cancer. AB - Despite a growing interest in development of non-cytotoxic targeted agents, systemic chemotherapy is still the mainstay of treatment for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, chemotherapy resistance limits our ability to effectively treat advanced lung cancer. Some lung tumors are intrinsically resistant to chemotherapy, and in virtually all cases, even the initial responders rapidly develop acquired resistance. While targeting histology could result in enhanced tumor sensitivity to a particular chemotherapeutic agent, better understanding of molecular determinants of chemotherapy sensitivity/resistance would be critically important. Development of predictive biomarkers to personalize chemotherapeutic agents and combining novel agents targeting specific resistance pathways with standard chemotherapy could be some promising strategies to overcome chemotherapy resistance in lung cancer. In this chapter, we will discuss some key mechanisms of resistance for commonly used chemotherapeutic agents in lung cancer. PMID- 26667346 TI - Current State of Metal-Based Drugs for the Efficient Therapy of Lung Cancers and Lung Metastases. AB - Lung cancer is the second most common cancer in both men and women and thus a leading cause of cancer-related deaths worldwide. New efficient treatments especially for its advanced stages and metastases are desperately needed, particularly with regard to overcoming the resistance which thwarts the efficacy of most clinically established drugs such as the platinum complexes. Glimpses of hope are new metal-based drugs that have emerged over the past decade which displayed efficacy in patients with platinum-resistant tumors and metastases. This chapter provides an overview of the latest developments of such metal-based drugs against lung cancer. PMID- 26667347 TI - Is obesity associated with healing after non-surgical periodontal therapy? A local vs. systemic evaluation. AB - BACKGROUND: We aimed to detect the role of obesity on the healing response to periodontal therapy in terms of serum lipids, C-reactive protein (CRP) and both serum and gingival crevicular fluid adipocytokines. MATERIAL AND METHODS: Thirty patients with periodontitis with (CPO) (n = 15) and without (n = 15) obesity and 15 healthy controls were included. Serum high-density lipoprotein, low-density lipoprotein, triglyceride, CRP levels and levels of adiponectin, interleukin (IL) 6, tumor necrosis factor (TNF)-alpha and IL-10 were evaluated before and 3 mo after initial periodontal therapy. Clinical periodontal measurements were also recorded at baseline and 3 mo. RESULTS: Periodontal parameters improved significantly in both periodontitis groups with or without obesity (p < 0.05) with no significant difference in terms of gain clinical attachment level (p > 0.05) and change in numbers of sites with probing depth >= 4 mm. High-density lipoprotein significantly increased in both groups (p > 0.05). CRP decreased significantly solely in the normal weight group. IL-6, IL-10 and TNF-alpha levels in gingival crevicular fluid improved significantly based on therapy in both groups (p < 0.05). Only TNF-alpha decreased significantly in the CPO, while adiponectin and IL-10 in addition to TNF-alpha improved significantly in the group of patients with periodontitis without obesity. CONCLUSION: Patients with CPO respond to periodontal therapy as well as the non-obese controls. This similar response is accompanied with consistent adipokine levels in gingival crevicular fluid. However, obesity affects the CRP and serum adipocytokine levels in response to therapy. PMID- 26667348 TI - Understanding hydrothermal transformation from Mn2O3 particles to Na0.55Mn2O4.1.5H2O nanosheets, nanobelts, and single crystalline ultra-long Na4Mn9O18 nanowires. AB - Manganese oxides are one of the most valuable materials for batteries, fuel cells and catalysis. Herein, we report the change in morphology and phase of as synthesized Mn2O3 by inserting Na(+) ions. In particular, Mn2O3 nanoparticles were first transformed to 2 nm thin Na0.55Mn2O4.1.5H2O nanosheets and nanobelts via hydrothermal exfoliation and Na cation intercalation, and finally to sub-mm ultra-long single crystalline Na4Mn9O18 nanowires. This paper reports the morphology and phase-dependent magnetic and catalytic (CO oxidation) properties of the as-synthesized nanostructured Na intercalated Mn-based materials. PMID- 26667349 TI - Presepsin and sepsis-induced acute kidney injury treated with continuous renal replacement therapy: will another promising biomarker bite the dust? PMID- 26667350 TI - Toward Effective Utilization of the Pediatric Emergency Department: The Case of ADHD. AB - This project's purpose was to characterize attention-deficit/hyperactivity disorder (ADHD)-related emergency department (ED) visits compared with other psychiatric visits made by children with Medicaid and to determine whether any visits were avoidable. Medicaid claims of children who visited the ED for mental health services were analyzed. Logistic regression was used to examine whether demographic, ED-, and system-level variables increased the odds of an ED visit for children with Medicaid, comparing those with ADHD to other psychiatric diagnoses. Children who were African American, arrived during the daytime, and lived in counties with mental health professional shortages had greater odds of an ED visit for ADHD compared to other psychiatric visits. Approximately 24% of all ED visits were for ADHD and about 30% of these visits may have been avoidable. ADHD-related ED visits comprise a sizeable proportion of all ED visits. Some visits appeared to be emergent but possibly treatable in primary care. PMID- 26667351 TI - Dynamics of low and high pathogenic avian influenza in wild and domestic bird populations. AB - This paper introduces a time-since-recovery structured, multi-strain, multi population model of avian influenza. Influenza A viruses infect many species of wild and domestic birds and are classified into two groups based on their ability to cause disease: low pathogenic avian influenza (LPAI) and high pathogenic avian influenza (HPAI). Prior infection with LPAI provides partial immunity towards HPAI. The model introduced in this paper structures LPAI-recovered birds (wild and domestic) with time-since-recovery and includes cross-immunity towards HPAI that can fade with time. The model has a unique disease-free equilibrium (DFE), unique LPAI-only and HPAI-only equilibria and at least one coexistence equilibrium. We compute the reproduction numbers of LPAI ([Formula: see text]) and HPAI ([Formula: see text]) and show that the DFE is locally asymptotically stable when [Formula: see text] and [Formula: see text]. A unique LPAI-only (HPAI only) equilibrium exists when [Formula: see text] ([Formula: see text]) and it is locally asymptotically stable if HPAI (LPAI) cannot invade the equilibrium, that is, if the invasion number [Formula: see text] ([Formula: see text]). We show using numerical simulations that the ODE version of the model, which is obtained by discarding the time-since-recovery structures (making cross-immunity constant), can exhibit oscillations, and also that the pathogens LPAI and HPAI can coexist with sustained oscillations in both populations. Through simulations, we show that even if both populations (wild and domestic) are sinks when alone, LPAI and HPAI can persist in both populations combined. Thus, reducing the reproduction numbers of LPAI and HPAI in each population to below unity is not enough to eradicate the disease. The pathogens can continue to coexist in both populations unless transmission between the populations is reduced. PMID- 26667352 TI - Neurobiologically Inspired Robotics: Enhanced Autonomy through Neuromorphic Cognition. PMID- 26667353 TI - Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information. AB - We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain's attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO's predictions and also lessons for neurobiologically inspired robotics emerging from this work. PMID- 26667354 TI - Texas Nurse Staffing Trends Before and After Mandated Nurse Staffing Committees. AB - This article describes the evolution of mandated nurse staffing committees in Texas from 2002 to 2009 and presents a study that analyzed nurse staffing trends in Texas using a secondary analysis of hospital staffing data (N = 313 hospitals) from 2000 to 2012 obtained from the American Hospital Association Annual Survey. Nurse staffing patterns based on three staffing variables for registered nurses (RNs), licensed vocational nurses (LVNs), and total licensed nurses were identified: full-time equivalents per 1,000 adjusted patient days, productive hours per adjusted patient day, and RN skill mix. Similar to national trends between 2000 and 2012, most Texas hospitals experienced an increase in RN and total nurse staffing, decrease in LVN staffing, and an increase in RN skill mix. The magnitude of total nurse staffing changes in Texas (5% increase) was smaller than national trends (13.6% increase). Texas's small, rural, government hospitals and those with the highest preregulation staffing levels experienced the least change in staffing between 2000 and 2012: median change of 0 to .13 full-time equivalents per 1,000 adjusted patient days and median change in productive hours per patient day of 0 to .23. The varying effects of staffing committees in different organizational contexts should be considered in future staffing legislative proposals and other policy initiatives. PMID- 26667355 TI - Parapheromones for Thynnine Wasps. AB - Sexually deceptive orchids produce floral volatiles that attract male insect pollinators. This interaction between flower and pollinator normally is highly specific. In the few cases where the chemical composition of the volatiles is known, the compounds have been found to be identical to those that comprise the sex pheromone of the female wasp. In this study, we investigated whether there is potential for flexibility in the molecular structure of the chemical cues used to mediate these specific interactions. Specifically, we asked whether strong sexual attraction can be maintained with structural modifications of sex pheromone components. Our study focused on the orchid, Drakaea glyptodon, which is pollinated by males of the thynnine wasp, Zaspilothynnus trilobatus. Three alkylpyrazines and a unique hydroxymethylpyrazine are components of the female produced sex pheromone of Z. trilobatus, and also the semiochemicals produced by the orchid that lures the males as pollinators. A blend of 2-butyl-3,5 dimethylpyrazine and 2-hydroxymethyl-3,5-diethyl-6-methylpyrazine (3:1) is as attractive as the full blend of four compounds. Therefore, in this study we substituted 2-hydroxymethyl-3,5-diethyl-6-methylpyrazine with one of five structurally related parapheromones in a blend with 2-butyl-3,5-dimethylpyrazine. All blends tested stimulated approaches by male wasps, with some also eliciting landing and attempted copulation. High-level calculations (G4(MP2)) showed the energy differences between the structural isomers were small, although the degree of sexual attraction varied, indicating the importance of structural factors for activity. One of the parapheromones, 2-hydroxymethyl-3,5-dimethyl-6 ethylpyrazine, elicited similar proportions of approaches, landings, and attempted copulations as the sex pheromone at the ratio and dose tested. The findings suggest that there is potential for chemical flexibility in the evolution of sexual deception. PMID- 26667356 TI - Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions. AB - In vitro-in vivo correlations (IVIVCs) play an important role in formulation development and drug approval. At the heart of IVIVC is deconvolution, the method of deriving an in vivo "dissolution profile" for comparison with in vitro dissolution data. IVIVCs are generally believed to be possible for highly permeable and highly soluble compounds with release/dissolution as the rate limiting step. In this manuscript, we apply the traditional deconvolution methods, Wagner-Nelson and numerical deconvolution, to profiles simulated using a simplified small intestine absorption and transit model. Small intestinal transit, dissolution, and absorption rate constants are varied across a range of values approximately covering those observed in the literature. IVIVC plots and their corresponding correlation coefficients are analyzed for each combination of parameters to determine the applicability of the deconvolution methods under a range of rate-limiting conditions. For highly absorbed formulations, the correlation coefficients obtained during IVIVC are comparable for both methods and steadily decline with decreasing dissolution rate and increasing transit rate. The applicability of numerical deconvolution to IVIVC is not greatly affected by absorption rate, whereas the applicability of Wagner-Nelson falls when dissolution rate overcomes absorption rate and absorption becomes the rate limiting step. The discrepancy between the expected and deconvolved input arises from the violation of a key assumption of deconvolution that the unknown input and unit impulse enter the system in the same location. PMID- 26667357 TI - Inhibition of the cardiac Na+ channel alpha-subunit Nav1.5 by propofol and dexmedetomidine. AB - Propofol and dexmedetomidine are very commonly used sedative agents. However, several case reports demonstrated cardiovascular adverse effects of these two sedatives. Both substances were previously demonstrated to quite potently inhibit neuronal voltage-gated Na(+) channels. Thus, a possible molecular mechanism for some of their cardiac side effects is an inhibition of cardiac voltage gated Na(+) channels. In this study, we therefore explored the effects of propofol and dexmedetomidine on the cardiac predominant Na(+) channel alpha-subunit Nav1.5. Effects of propofol and dexmedetomidine were investigated on constructs of the human alpha-subunit Nav1.5 stably expressed in HEK-293 cells by means of whole cell patch clamp recordings. Both agents induced a concentration-dependent tonic inhibition of Nav1.5. The calculated IC50 value for propofol was 228 +/- 10 MUM, and for dexmedetomidine 170 +/- 20 MUM. Tonic block only marginally increased on inactivated channels, and a weak use-dependent block at 10 Hz was observed for dexmedetomidine (16 +/- 2 % by 100 MUM). The voltage dependencies of fast and slow inactivation as well as the time course of recovery from inactivation were shifted by both propofol and dexmedetomidine. Propofol (IC50 126 +/- 47 MUM) and dexmedetomidine (IC50 182 +/- 27 MUM) blocked the persistent sodium current induced by veratradine. Finally, the local-anesthetic (LA)-insensitive mutant Nav1.5-F1760A exhibited reduced tonic and use-dependent block by both substances. Dexmedetomidine was generally more potent as compared to propofol. Propofol and dexmedetomidine seem to interact with the LA-binding site to inhibit the cardiac Na(+) channel Nav1.5 in a state-dependent manner. These data suggest that Nav1.5 is a hitherto unrecognized molecular component of some cardiovascular side effects of these sedative agents. PMID- 26667359 TI - Problems with study on secondhand smoke and children's tooth enamel. PMID- 26667360 TI - Realizing Broadband and Invertible Linear-to-circular Polarization Converter with Ultrathin Single-layer Metasurface. AB - The arbitrary control of the polarization states of light has attracted the interest of the scientific community because of the wide range of modern optical applications that such control can afford. However, conventional polarization control setups are bulky and very often operate only within a narrow wavelength range, thereby resisting optical system miniaturization and integration. Here, we present the basic theory, simulated demonstration, and in-depth analysis of a high-performance broadband and invertible linear-to-circular (LTC) polarization converter composed of a single-layer gold nanorod array with a total thickness of ~lambda/70 for the near-infrared regime. This setup can transform a circularly polarized wave into a linearly polarized one or a linearly polarized wave with a wavelength-dependent electric field polarization angle into a circularly polarized one in the transmission mode. The broadband and invertible LTC polarization conversion can be attributed to the tailoring of the light interference at the subwavelength scale via the induction of the anisotropic optical resonance mode. This ultrathin single-layer metasurface relaxes the high precision requirements of the structure parameters in general metasurfaces while retaining the polarization conversion performance. Our findings open up intriguing possibilities towards the realization of novel integrated metasurface based photonics devices for polarization manipulation, modulation, and phase retardation. PMID- 26667358 TI - The sexual health of female rectal and anal cancer survivors: results of a pilot randomized psycho-educational intervention trial. AB - BACKGROUND: Sexual dysfunction is a frequently reported consequence of rectal/anal cancer treatment for female patients. PURPOSE: The purpose of this study was to conduct a small randomized controlled trial to assess the efficacy of a telephone-based, four-session Cancer Survivorship Intervention-Sexual Health (CSI-SH). METHODS: Participants (N = 70) were stratified by chemotherapy, stoma, and menopause statuses before randomization to CSI-SH or assessment only (AO). Participants were assessed at baseline, 4 months (follow-up 1), and 8 months (follow-up 2). RESULTS: The intervention had medium effect sizes from baseline to follow-up 1, which decreased by follow-up 2. Effect sizes were larger among the 41 sexually active women. Unadjusted means at the follow-ups were not significantly different between the treatment arms. Adjusting for baseline scores, demographics, and medical variables, the intervention arm had significantly better emotional functioning at follow-ups 1 and 2 and less cancer specific stress at follow-up 1 compared to the AO arm. CONCLUSION: The data supported the hypothesized effects on improved sexual and psychological functioning and quality of life in CSI-SH female rectal/anal cancer survivors compared to the AO condition. This pilot study (N = 70) of CSI-SH supported the impact of this intervention on sexual and psychological functioning and quality of life on rectal and anal cancer survivors compared with an AO condition. However, intervention effects were stronger at follow-up 1 as compared to follow up 2 and were stronger for sexually active women. IMPLICATIONS FOR CANCER SURVIVORS: Women may benefit from a brief, four-session, sexual health intervention after treatment from rectal and anal cancer. PMID- 26667361 TI - The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension. AB - Thrombosis and inflammation are two major factors underlying chronic thromboembolic pulmonary hypertension (CTEPH). Tissue factor (TF), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1) may play critical roles in the process of CTEPH thrombosis and pulmonary vascular remodeling. Ten patients with a confirmed diagnosis of CTEPH, 20 patients with acute pulmonary thromboembolism and 15 patients with other types of pulmonary hypertension were enrolled in this study, along with 20 healthy subjects as the control group. The immunoturbidimetric method was used to determine the plasma content of CRP. The plasma levels of TNF alpha, MCP-1, and TF antigen were measured by an enzyme-linked immunosorbent assay, and TF activity was measured by the chromogenic substrate method. Percoll density gradient centrifugation was used to separate peripheral blood mononuclear cells from plasma. The level of monocyte TF mRNA was examined by reverse transcriptase-polymerase chain reaction. The correlations between all indices described above were analyzed. In CTEPH patients, the expression of CRP, TNF alpha, and MCP-1 was significantly higher than that in controls (P < 0.05). The levels of TF activity, TF antigen, and TF mRNA in monocyte cells were increased in CTEPH patients when compared with control subjects, but only the TF antigen and TF mRNA levels were significantly different (P < 0.05). In CTEPH patients, levels of CRP, MCP-1, and TNF-alpha significantly correlated with the level of TF antigen in plasma. TF gene expression was increased in patients with CTEPH, suggesting that blood-borne TF mainly comes from mononuclear cells. TF expression significantly correlated with levels of CRP, TNF-alpha and MCP-1. These factors may play an important role in the development of CTEPH via the inflammation coagulation-thrombosis cycle. PMID- 26667362 TI - The Role of Direct-Fed Microbials in Conventional Livestock Production. AB - Supplementation of direct-fed microbials (DFM) as a means to improve the health and performance of livestock has generated significant interest over the past 15+ years. A driving force for this increased interest in DFM is to reduce or eliminate the use of low-dose antibiotics in livestock production. This increased attention toward DFM supplementation has generated an extensive body of research. This effort has resulted in conflicting reports. Although there has been considerable variation in the design of these studies, one of the main causes for this lack of consistency may be attributed to the variation in the experimental immune challenge incorporated to evaluate DFM supplementation. Taking into account the experimental immune challenge, there is strong evidence to suggest that DFM supplementation may have an impact on the immune response, overall health, and performance of livestock. PMID- 26667363 TI - Effect of dietary fibres on small intestine histomorphology and lipid metabolism in young broiler chickens. AB - Two experiments were conducted to determine the influence of dietary fibres on small intestine histomorphology and lipid metabolism in broilers from 1 to 21 day of age. In experiment 1, diets containing insoluble [cellulose (CEL); 2% and 4%] or soluble [carboxymethyl cellulose (CMC); 2% and 4%] fibre were fed to broilers from day 1 to 21 post-hatch and ileal tissue was collected at day 21 of age for histological evaluation. In experiment 2, broilers diet was supplemented with 0%, 1% or 2% insoluble fibre (Arbocel) during day 7 to 21 post-hatch and plasma and liver lipid metabolism were evaluated at day 21. In experiment 1, inclusion of CMC reduced body weight gain (BWG) and feed intake (FI) and increased feed conversion ratio (FCR) compared with others. Intestinal histomorphology was unaffected by CEL, but CMC led to an increase in crypt depth (CD) and serosa thickness and a decrease in villus height (VH), villus width (VW), VH:CD ratio and villus surface area (VSA), rather than control and CEL groups. Treatment did not affect goblet cell type. Moreover, the CMC-fed birds had greater total goblet cell count (GCC) as compared with others. In experiment 2, fibre inclusion was associated with increases in BWG from 7 to 14 day of age and an improvement in FCR, whereas FI was not influenced by treatments. Inclusion of fibre in the diet decreased the weight of the abdominal fat and cholesterol concentrations of liver and plasma. No significant effects on fatty acid composition of liver lipid were observed by fibre supplementation. These findings suggest dietary fibre affects performance, intestinal histomorphology and lipid metabolism in young chicks, which may directly affect poultry feeding strategies. PMID- 26667364 TI - Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult. AB - BACKGROUND: During osteoarthritis and following surgical procedures, the environment of the knee is rich in proinflammatory cytokines such as IL-1. Introduction of tissue-engineered cartilage constructs to a chemically harsh milieu may limit the functionality of the implanted tissue over long periods. A chemical preconditioning scheme (application of low doses of IL-1) was tested as a method to prepare developing engineered tissue to withstand exposure to a higher concentration of the cytokine, known to elicit proteolysis as well as rapid degeneration of cartilage. METHODS: Using an established juvenile bovine model system, engineered cartilage was preconditioned with low doses of IL-1alpha (0.1 ng/mL, 0.5 ng/mL, and 1.0 ng/mL) for 7 days before exposure to an insult dose (10 ng/mL). The time frame over which this protection is afforded was investigated by altering the amount of time between preconditioning and insult as well as the time following insult. To explore a potential mechanism for this protection, one set of constructs was preconditioned with CoCl2, a chemical inducer of hypoxia, before exposure to the IL-1alpha insult. Finally, we examined the translation of this preconditioning method to extend to clinically relevant adult, passaged chondrocytes from a preclinical canine model. RESULTS: Low doses of IL-1alpha (0.1 ng/mL and 0.5 ng/mL) protected against subsequent catabolic degradation by cytokine insult, preserving mechanical stiffness and biochemical composition. Regardless of amount of time between preconditioning scheme and insult, protection was afforded. In a similar manner, preconditioning with CoCl2 similarly allowed for mediation of catabolic damage by IL-1alpha. The effects of preconditioning on clinically relevant adult, passaged chondrocytes from a preclinical canine model followed the same trends with low-dose IL-1beta offering variable protection against insult. CONCLUSIONS: Chemical preconditioning schemes have the ability to protect engineered cartilage constructs from IL-1-induced catabolic degradation, offering potential modalities for therapeutic treatments. PMID- 26667365 TI - Missed losses loom larger than missed gains: Electrodermal reactivity to decision choices and outcomes in a gambling task. AB - Loss aversion is a defining characteristic of prospect theory, whereby responses are stronger to losses than to equivalently sized gains (Kahneman & Tversky Econometrica, 47, 263-291, 1979). By monitoring electrodermal activity (EDA) during a gambling task, in this study we examined physiological activity during risky decisions, as well as to both obtained (e.g., gains and losses) and counterfactual (e.g., narrowly missed gains and losses) outcomes. During the bet selection phase, EDA increased linearly with bet size, highlighting the role of somatic signals in decision-making under uncertainty in a task without any learning requirement. Outcome-related EDA scaled with the magnitudes of monetary wins and losses, and losses had a stronger impact on EDA than did equivalently sized wins. Narrowly missed wins (i.e., near-wins) and narrowly missed losses (i.e., near-losses) also evoked EDA responses, and the change of EDA as a function of the size of the missed outcome was modestly greater for near-losses than for near-wins, suggesting that near-losses have more impact on subjective value than do near-wins. Across individuals, the slope for choice-related EDA (as a function of bet size) correlated with the slope for outcome-related EDA as a function of both the obtained and counterfactual outcome magnitudes, and these correlations were stronger for loss and near-loss conditions than for win and near-win conditions. Taken together, these asymmetrical EDA patterns to objective wins and losses, as well as to near-wins and near-losses, provide a psychophysiological instantiation of the value function curve in prospect theory, which is steeper in the negative than in the positive domain. PMID- 26667366 TI - More emotional facial expressions during episodic than during semantic autobiographical retrieval. AB - There is a substantial body of research on the relationship between emotion and autobiographical memory. Using facial analysis software, our study addressed this relationship by investigating basic emotional facial expressions that may be detected during autobiographical recall. Participants were asked to retrieve 3 autobiographical memories, each of which was triggered by one of the following cue words: happy, sad, and city. The autobiographical recall was analyzed by a software for facial analysis that detects and classifies basic emotional expressions. Analyses showed that emotional cues triggered the corresponding basic facial expressions (i.e., happy facial expression for memories cued by happy). Furthermore, we dissociated episodic and semantic retrieval, observing more emotional facial expressions during episodic than during semantic retrieval, regardless of the emotional valence of cues. Our study provides insight into facial expressions that are associated with emotional autobiographical memory. It also highlights an ecological tool to reveal physiological changes that are associated with emotion and memory. PMID- 26667367 TI - Effects of the Addition of Eicosapentaenoic Acid to Strong Statin Therapy on Inflammatory Cytokines and Coronary Plaque Components Assessed by Integrated Backscatter Intravascular Ultrasound. AB - BACKGROUND: The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known. METHODS AND RESULTS: A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5 +/- 1.3 to 15.0 +/- 1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9 +/- 0.8 to 25.6 +/- 1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3 +/ 2.1 to 2.6 +/- 1.2 ng/ml, 120.4 +/- 26.2 to 110.2 +/- 26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group. CONCLUSIONS: The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines. PMID- 26667368 TI - Is New-Onset Atrial Fibrillation Bad News for Patients With Heart Failure? PMID- 26667369 TI - Report of the American Heart Association (AHA) Scientific Sessions 2015, Orlando. AB - The American Heart Association Scientific Sessions were held in Orlando on November 7-15, 2015. The meeting attracted more than 18,000 participants, including physicians, research scientists, students, and paramedical personnel, from more than 100 countries. Sessions over the 5 days included a comprehensive and unparalleled education delivered via more than 5,000 presentations, with 1,000 invited faculty members and 4,000 abstract presentations from the world leaders in cardiovascular disease. It also displayed the newest cardiovascular technology and resources by more than 200 exhibitors. There were 19 trials scheduled in 6 late-breaking clinical trial sessions. The Systolic Blood Pressure Intervention Trial (SPRINT) aimed to determine the most appropriate targets for the systolic blood pressure among persons without diabetes. A total of 9,361 persons with systolic blood pressure of >=130 mmHg and an increased cardiovascular risk, but without diabetes, were randomly assigned to a target systolic blood pressure of <120 mmHg (intensive treatment) or a target of <140 mmHg (standard treatment). A significantly lower rate of the primary composite outcome and all-cause mortality in the intensive-treatment group than in the standard-treatment group was observed. Summaries and overviews of the late breaking trials, clinical science special report sessions, and sessions to which members of the Japanese Circulation Society contributed are presented. PMID- 26667370 TI - Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association. AB - Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course. PMID- 26667371 TI - Anterior Cruciate Ligament Injuries in Professional Hockey Players. AB - BACKGROUND: Performance outcomes and return-to-play data have been reported after anterior cruciate ligament (ACL) injuries in professional football and basketball, but they have rarely been reported in professional hockey. HYPOTHESIS: The hypothesis was that performance after ACL reconstruction would be comparable to prior levels of play in a series of National Hockey League (NHL) players. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The NHL Injury Surveillance System (ISS) was utilized to identify all players with an ACL injury between 2006 and 2010. Medical staff members for all NHL teams were surveyed regarding these injuries. The medical staff completed a questionnaire for each injury, and statistics were analyzed using multiple analyses of variance to compare outcomes, performance, and the complication rate. A control group was identified and matched based on performance, career length before injury, age, height, and weight. RESULTS: There were 47 players identified by the NHL ISS. There were 3 goalies, 8 defensemen, and 36 wings or centers. The average age of these players was 27.69 years. The average length of time played after the injury was 2.8 years, which was less than that of the control group (4.4 years) (P = .004). The presence of a meniscal injury was associated with a decreased length of career compared with the control group (P = .012) and with patients with an isolated ACL injury (P = .002). For wings and centers, the number of games played decreased from 71.2 to 58.2 in the first full season after the injury (P = .05) and to 59.29 in the second season (P = .03). In the first season after the injury, for forwards and wings, assists and total points decreased from 20.3 and 35.2 to 13.8 (P = .005) and 25.9 (P = .018), respectively. In the second season after the injury, assists and goals decreased to 10.0 (P = .002) and 10.0 (P = .013), respectively. Compared with controls, the per-season averages of goals (P = .001), assists (P = .010), and total points (P = .004) decreased. Four players (8.5%) had subsequent failure of reconstruction, and there was a total reoperation rate of 20%. Five players (10.6%) did not return to play, and 4 (8.5%) were unable to return to play for a full season. CONCLUSION: Most players are able to return to play in the NHL after an ACL injury. However, career length and performance may be significantly decreased compared with controls. This may represent a more severe initial injury, and more focused return-to-play pathways may identify barriers to return to play. PMID- 26667372 TI - Variability of innate immune system genes in Native American populations relationship with history and epidemiology. AB - OBJECTIVES: The immune system of a host, defending him/her against invading pathogens, has two main subsystems: innate immunity and acquired immunity. There are several evidences showing that Native American populations are immunologically different from non-Native populations. Our aim was to describe the variability of innate immune system genes in Native American populations. MATERIALS AND METHODS: We investigated heterozygozities and patterns of population differentiation (FST ) of 14 polymorphisms related to the innate immune response in five Native American populations (Ache, Guarani-Kaiowa, Guarani-Nandeva, Kaingang, and Xavante) and the results were compared with the three major world population data (YRI, CEU, and CHB) available at the 1,000 genomes database. RESULTS: Mean heterozygosities ranged between 0.241 +/- 0.057 (Ache) and 0.343 +/- 0.033 (Kaingang), but no significant differences were observed (Friedman test, P = 0.197). Mean heterozygosities were also not significantly different when Amerindians were pooled and compared with the 1000 genomes populations (Friedman test, P = 0.506). When the Native American populations were grouped as Amerindians, a significantly higher FST value (0.194) was observed between the Amerindian and African populations. The Ewens-Watterson neutrality test showed that these markers are not under strong selective pressure. DISCUSSION: Native American populations present similar levels of heterozygosity as those of other continents, but are different from Africans in the frequency of polymorphisms of innate immune genes. This higher differentiation is probably due to demographic processes that occurred during the out-of-Africa event. PMID- 26667373 TI - Bortezomib for antibody-mediated rejection in a young lung transplant recipient. PMID- 26667375 TI - Epidemiological investigation of suspected autism in children and implications for healthcare system: a mainstream kindergarten-based population study in Longhua District, Shenzhen. AB - BACKGROUND: Individuals with autism put a heavy demand on medical services, and prevalence estimates are needed for the planning of such services. Screening for autism in children has important implications for individuals and policy makers. This study aimed to estimate prevalence of suspected autism in children in Longhua District, Shenzhen, and to investigate risk factors for autism. METHODS: A cross-sectional study was conducted in Longhua District, Shenzhen in October 2014. A total of 141 kindergartens were approached and consented to participate in the current study. All children who met the inclusion criteria were screened for autism by using the Autism Behavior Checklist (ABC). RESULTS: 15,200 children in total completed the survey and were included in the final analysis. 2.6 % (95 % CI 2.3-2.9) respondents had a high probability of autism, while 4.0 % (95 % CI 3.7-4.3) respondents had questionable autism. Male children were more likely to develop autism when compared with their female counterparts (P < 0.001). Children of mothers with a lower education level and younger age tended to develop autism (P < 0.001). CONCLUSIONS: Our study shows a high prevalence rate of suspected autism in children which suggests an urgent need of early detection of autism with ABC across the Shenzhen city, or even around China. Further studies with diagnostic procedure are warranted. Maternal age and education level, and gender of children are possible factors related to autism. PMID- 26667376 TI - Antibodies to microtubule-associated protein-2 in the cerebrospinal fluid are a useful diagnostic biomarker for neuropsychiatric systemic lupus erythematosus. AB - OBJECTIVE: Previous reports indicate that serum anti-microtubule-associated protein 2 (MAP-2) antibodies are common in sera from patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Differential diagnosis of NPSLE is occasionally difficult because of differential diagnosis which can mimic NPSLE. Therefore, specific biomarkers for NPSLE are needed. We conducted this study to clarify whether cerebrospinal fluid (CSF) anti-MAP-2 antibodies are a useful diagnostic biomarker for NPSLE. METHODS: Enzyme-linked immunosorbent assay was conducted to measure CSF concentrations of anti-MAP-2 and anti-ribosomal P antibodies and of IL-6 in NPSLE patients (n = 24) and non-NPSLE controls (n = 17). The non-NPSLE controls consisted of systemic lupus erythematosus patients with neuropsychiatric symptoms caused by non-NPSLE conditions (n = 10) and patients with other connective tissue diseases (n = 7). RESULTS: Significantly higher anti-MAP-2 antibody titers were found in the CSF of patients with NPSLE versus non-NPSLE controls. The prevalence of anti-MAP-2 antibodies was 33.3% (8/24) in NPSLE patients when a positive cutoff value was 3 standard deviations above the mean optical density of non-NPSLE controls. None of the controls had anti-MAP-2 antibodies in their CSF. Both anti-ribosomal P antibody titers and concentration of IL-6 in the CSF were significantly higher in patients with NPSLE having anti-MAP-2 antibodies than in patients with non-NPSLE controls. CONCLUSION: Anti-MAP-2 antibodies could be detected in the CSF of 33.3% of patients with NPSLE, and its presence was highly specific for NPSLE. We propose that CSF anti-MAP-2 antibodies are a novel and useful diagnostic biomarker for NPSLE. PMID- 26667374 TI - Modeling neurodevelopmental cognitive deficits in tasks with cross-species translational validity. AB - Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to 'develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures' in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross-species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains. PMID- 26667377 TI - Eradication of Invading Insect Populations: From Concepts to Applications. AB - Eradication is the deliberate elimination of a species from an area. Given that international quarantine measures can never be 100% effective, surveillance for newly arrived populations of nonnative species coupled with their eradication represents an important strategy for excluding potentially damaging insect species. Historically, eradication efforts have not always been successful and have sometimes been met with public opposition. But new developments in our understanding of the dynamics of low-density populations, the availability of highly effective treatment tactics, and bioeconomic analyses of eradication strategies offer new opportunities for developing more effective surveillance and eradication programs. A key component that connects these new developments is the harnessing of Allee effects, which naturally promote localized species extinction. Here we review these developments and suggest how research might enhance eradication strategies. PMID- 26667378 TI - Ecology of Varroa destructor, the Major Ectoparasite of the Western Honey Bee, Apis mellifera. AB - Varroa destructor is the most important ectoparasite of Apis mellifera. This review addresses the interactions between the varroa mite, its environment, and the honey bee host, mediated by an impressive number of cues and signals, including semiochemicals regulating crucial steps of the mite's life cycle. Although mechanical stimuli, temperature, and humidity play an important role, chemical communication is the most important channel. Kairomones are used at all stages of the mite's life cycle, and the exploitation of bees' brood pheromones is particularly significant given these compounds function as primer and releaser signals that regulate the social organization of the honey bee colony. V. destructor is a major problem for apiculture, and the search for novel control methods is an essential task for researchers. A detailed study of the ecological interactions of V. destructor is a prerequisite for creating strategies to sustainably manage the parasite. PMID- 26667379 TI - What Can Plasticity Contribute to Insect Responses to Climate Change? AB - Plastic responses figure prominently in discussions on insect adaptation to climate change. Here we review the different types of plastic responses and whether they contribute much to adaptation. Under climate change, plastic responses involving diapause are often critical for population persistence, but key diapause responses under dry and hot conditions remain poorly understood. Climate variability can impose large fitness costs on insects showing diapause and other life cycle responses, threatening population persistence. In response to stressful climatic conditions, insects also undergo ontogenetic changes including hardening and acclimation. Environmental conditions experienced across developmental stages or by prior generations can influence hardening and acclimation, although evidence for the latter remains weak. Costs and constraints influence patterns of plasticity across insect clades, but they are poorly understood within field contexts. Plastic responses and their evolution should be considered when predicting vulnerability to climate change-but meaningful empirical data lag behind theory. PMID- 26667380 TI - Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment. AB - AIM: Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. METHODS: Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. RESULTS: Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted. CONCLUSION: Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages. PMID- 26667381 TI - Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana. AB - Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function. PMID- 26667383 TI - Similar But Different: A Comparison of Adnexal Torsion in Pediatric, Adolescent, and Pregnant and Reproductive-Age Women. AB - BACKGROUND: We sought to investigate and compare the clinical presentation, ultrasound findings, surgical characteristics, and causes of adnexal torsion among three groups: pediatric and adolescent population, reproductive-age women, and pregnant women. MATERIAL AND METHODS: Two hundred twenty-seven surgically confirmed episodes of adnexal torsion in 199 patients treated in our department from January 2008 to December 2014 were retrospectively analyzed. RESULTS: Abdominal pain duration of >24 hours before emergency room presentation was more common in pediatric and adolescent patients compared with reproductive-age and pregnant women (42.3% vs. 28.4% and 15.5%, respectively, p = 0.04). However, there was no difference between the groups in the time interval from their emergency room admission to surgery. Torsion of "normal adnexa" occurred in 11/44 (25.0%) of pediatric and adolescent patients, 30/99 (30.3%) of reproductive-age patients, and 12/56 (21.4%) of pregnant patients, while torsion involving multicystic ovaries occurred in 0%, 4%, and 32.1%, respectively, torsion involving paraovarian cysts occurred in 20.5%, 14.1%, and 1.8%, respectively, and torsion involving benign dermoid cysts occurred in 4.5%, 15.2%, and 5.4%, respectively (p < 0.001). Torsion involving supposedly functional ovarian cysts occurred in 45.5%, 34.3%, and 69.6%, respectively (p < 0.001). The torsion recurrence rates were 18.2% in the pediatric subjects, 19.2% in reproductive-age women, and 10.7% in pregnant women (p = 0.3). CONCLUSIONS: The presentation of adnexal torsion is similar in pediatric and reproductive-age and pregnant women, although the underlying adnexal pathology may be different. Functional ovarian cysts cause the majority of torsion cases in pregnant women. Recurrence of torsion may occur in any age group. PMID- 26667382 TI - A clinical trial to examine disparities in quitting between African-American and White adult smokers: Design, accrual, and baseline characteristics. AB - BACKGROUND: African-Americans smoke fewer cigarettes per day than Whites but experience greater smoking attributable morbidity and mortality. African-American White differences may also exist in cessation but rigorously designed studies have not been conducted to empirically answer this question. METHODS/DESIGN: Quit2Live is, to our knowledge, the first head-to-head trial designed with the primary aim of examining African-American-White disparities in quitting smoking. Secondary aims are to identify mechanisms that mediate and/or moderate the relationship between race and quitting. The study is ongoing. Study aims are accomplished through a 5-year prospective cohort intervention study designed to recruit equal numbers of African-Americans (n=224) and Whites (n=224) stratified on age (<40, >=40) and gender, key factors known to impact cessation, and all within a restricted income range (<=400% federal poverty level). All participants will receive 12 weeks of varenicline in combination with smoking cessation counseling. The primary outcome is cotinine-verified 7-day point prevalence abstinence from smoking at week 26. Secondary outcomes are cotinine-verified 7 day point prevalence abstinence from smoking at weeks 4 and 12. DISCUSSION: Findings from Quit2Live will not only address if African-American-White disparities in quitting smoking exist but, more importantly, will examine mechanisms underlying the difference. Attention to proximal, modifiable mechanisms (e.g., adherence, response to treatment, depression, stress) maximizes Quit2Live's potential to inform practice. Findings will provide an empirically derived approach that will guide researchers and clinicians in identifying specific factors to address to improve cessation outcomes and reduce tobacco related morbidity and mortality in African-American and White smokers. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01836276. PMID- 26667386 TI - Postural Assessment Scale for Stroke Patients Scores as a predictor of stroke patient ambulation at discharge from the rehabilitation ward. AB - OBJECTIVE: The Postural Assessment Scale for Stroke Patients (PASS) is used to assess static and dynamic balance of stroke patients. PASS has demonstrated good measurement properties for reliability and validity, but its predictive effect for ambulation in stroke patients has not been investigated. The aim of this study was to investigate the predictive value of PASS for ambulation in patients with stroke after inpatient rehabilitation. METHODS: In this retrospective study, a total of 341 stroke patients were recruited from a rehabilitation ward of a medical university hospital. Patients were assessed at baseline using PASS and observation of rolling ability, and divided into 2 groups at discharge: independently ambulatory (n = 246) and non-ambulatory (n = 95). Receiver operating characteristic curve and adjusted bivariate logistic regression was applied to analyse the predictive value of baseline PASS scores, variables of demographic data, and rolling ability at admission to inpatient rehabilitation. RESULTS: For all stroke patients, mean admission to the rehabilitation ward was 34.40 days after stroke and mean length of hospitalization 18.12 days. The receiver operating characteristic curve was obtained with a cut-off score of 3.5 points for static PASS, 8.5 points for dynamic PASS, and 12.5 points for total PASS, demonstrating the highest percentage of accurately predicted ability of independently walking at discharge. Adjusted bivariate logistic regression found rolling ability, static PASS and dynamic PASS to be predictors for ambulation of stroke patients at discharge. CONCLUSION: Initial static PASS score, dynamic PASS score and rolling can be predictors for independent ambulation of stroke patients after a course of inpatient rehabilitation. PMID- 26667385 TI - Out of southern East Asia: the natural history of domestic dogs across the world. AB - The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth. PMID- 26667387 TI - Enantioselective Hydrosilylation of Imines Catalyzed by Chiral Zinc Acetate Complexes. AB - A series of zinc acetate complexes with optically pure diphenylethanediamine (DPEDA)-derived ligands have been employed as enantioselective catalyst for the hydrosilylation of various imines. High control of stereoselectivity (up to 97% ee) and excellent yields (up to 96%) were gained for a broad range of N phosphinoylimines by using (R,R)-N,N'-dibenzyl-1,2-diphenylethane-1,2-diamine. This is the first successful application of an air-stable and environmentally friendly chiral Zn(OAc)2 complex instead of the previously used harmful diethylzinc in the asymmetric reduction of the C?N double bond. PMID- 26667388 TI - Erratum: The genomics of ecological vicariance in threespine stickleback fish. PMID- 26667389 TI - The implications of high-quality staff break areas for nurses' health, performance, job satisfaction and retention. AB - AIM: The main study objective was to explore policy and design factors contributing to nurses' perception of how well-designed staff break areas can play an important beneficial role in relation to their overall job satisfaction, retention, performance and job-related health concerns. BACKGROUND: Nurses are extremely valuable to the healthcare industry; however, today's nursing profession is challenged by nurses' fatigue and its negative consequences on nurses' health and the quality of patient care they provide. METHODS: Preliminary interviews were conducted with 10 nurses who worked as consultants in the healthcare design and construction industry. Based on findings, an online survey was developed and distributed to over 10 000 members of the Academy of Medical Surgical Nurses in the United States. RESULTS: The majority of nurses viewed high quality break spaces as 'fairly' or 'very' important in terms of their potential to positively influence staff, patient and facility outcomes. Stress, rest breaks and the quality of break areas were some of the significant factors contributing to their perception. CONCLUSION/IMPLICATIONS FOR NURSING MANAGEMENT: The results of this empirical study support the conclusion that improvements in healthcare facility policies regarding staff breaks, as well as the creation of better designed break areas, can be of significant benefit for nurses and the patients that they serve. PMID- 26667392 TI - Vascular Complications Arising from Hemostasis with Manual Compression Following Extracorporeal Membrane Oxygenation Decannulation. AB - BACKGROUND: We evaluated the vascular complications and success rate of manual compression in achieving hemostasis and access site closure after transfemoral arterial extracorporeal membrane oxygenation (ECMO) decannulation. METHODS: Between February 2010 and July 2014, 63 patients who underwent veno-arterial ECMO were retrospectively studied. Patients who developed postprocedural vascular complications after manual compression were identified, and the hemostasis success rate was evaluated. RESULTS: The overall manual compression success rate was 95.2%. Eleven patients (17.5%) developed vascular complications: hematoma (more than 5 cm) occurred in six patients (9.5%) who were treated with repeat manual compression. Retroperitoneal bleeding occurred in one patient, requiring abdominal hematoma evacuation surgery. One patient (1.6%) developed access site bleeding, requiring suturing. One patient (1.6%) developed an arteriovenous fistula (AVF). Two patients (3.2%) had a pseudoaneurysm, of whom one was treated with sclerotherapy in the femoral artery; the other patient and the AVF patient were treated with repeat manual compression. The hematoma rate was significantly higher in patients with an activated partial thromboplastin time (aPTT) >56, and in whom dual antiplatelet drugs were used (OR: 11.55, 95% CI: 1.32-100.92, p = 0.027; OR: 8.17, CI: 1.61-41.46, p = 0.011, respectively). CONCLUSION: The use of dual antiplatelet drugs and a higher aPTT can lead to an increased risk of post procedural vascular complications. Therefore, manual compression should be applied cautiously after the correction of coagulopathy factors such as activated clotting time (ACT), aPTT, and platelets. PMID- 26667390 TI - CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system. AB - BACKGROUND: Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. METHODS: We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni's post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means +/- SEM. Differences were considered significant if P <= 0.05. RESULTS: As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5(-/-) mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5(-/-) mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5(-/-) mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5(-/-) mice, however, were associated with decreased numbers of infiltrating mononuclear cells and increased permeability of the blood brain barrier. CONCLUSIONS: These data indicate that regional differences in chemokine expression occur in response to WNV infection of the CNS, and that cortical neurons require CCR5 activity to limit viral burden in this brain region. PMID- 26667391 TI - The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development. AB - TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of the pre-erythrocytic stage is still largely unknown. Here, we found that sporozoite and its lysate could significantly activate the TLR2, and induce macrophages to release proinflammatory cytokines, including IL-6, MCP-1 and TNF-alpha, in a TLR2 dependent manner. Further studies showed that sporozoite and its lysate could be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers, implicating the complexity of TLR2 agonist in sporozoite. Interestingly, the TLR2 signaling can significantly suppress the development of the pre-erythrocytic stage of Plasmodium yoelii, as both liver parasite load and subsequent parasitemia were significantly elevated in both TLR2- and MyD88-deficient mice. Additionally, the observed higher level of parasite burden in TLR2(-/-) mice was found to be closely associated with a reduction in proinflammatory cytokines in the liver. Therefore, we provide the first evidence that sporozoites can activate the TLR2 signaling, which in turn significantly inhibits the intrahepatic parasites. This may provide us with novel clues to design preventive anti-malaria therapies. PMID- 26667393 TI - Circulating multimarker profile of patients with symptomatic heart failure supports enhanced fibrotic degradation and decreased angiogenesis. AB - BACKGROUND: Heart failure (HF) involves myocardial fibrosis and dysregulated angiogenesis. OBJECTIVE: We explored whether biomarkers of fibrosis and angiogenesis correlate with HF severity. METHODS: Biomarkers of fibrosis [procollagen types I and III (PIP and P3NP), carboxyterminal-telopeptide of type I collagen (ICTP), matrix metalloproteases (MMP2 and MMP9), tissue inhibitor of MMP1 (TIMP1)]; and angiogenesis [placental growth factor (PGF), vascular endothelial growth factor (VEGF), soluble Fms-like tyrosine kinase-1 (sFlt1)] were measured in 52 HF patients and 19 controls. RESULTS: P3NP, ICTP, MMP2, TIMP1, PGF, and sFlt1 levels were elevated in HF, while PIP/ICTP, PGF/sFlt1, and VEGF/sFlt1 ratios were reduced. PIP/ICTP, MMP-9/TIMP1, and VEGF/sFlt1 ratios were lowest among patients with severe HF. CONCLUSIONS: Severe HF is associated with collagen breakdown and reduced angiogenesis. A multimarker approach may guide therapeutic targeting of fibrosis and angiogenesis in HF. PMID- 26667394 TI - Eight years' experience with a Medical Education Journal Club in Mexico: a quasi experimental one-group study. AB - BACKGROUND: A time-honored strategy for keeping up to date in medicine and improving critical appraisal skills is the Journal Club (JC). There are several reports of its use in medicine and allied health sciences but almost no reports of JC focused on medical education. The purpose of the study is to describe and evaluate an eight years' experience with a medical education Journal Club (MEJC). METHODS: We started a monthly medical education JC in 2006 at UNAM Faculty of Medicine in Mexico City. Its goal is to provide faculty with continuing professional development in medical education. A discussion guide and a published paper were sent 2 weeks before sessions. We reviewed the themes and publication types of the papers used in the sessions, and in June-July 2014 administered a retrospective post-then-pre evaluation questionnaire to current participants that had been regular attendees to the JC for more than 2 years. The retrospective post-then-pre comparisons were analyzed with Wilcoxon signed-rank test. Effect sizes were calculated for the pre-post comparisons with Cohen's r. RESULTS: There have been 94 MEJC sessions until July 2014. Average attendance is 20 persons, a mix of clinicians, educators, psychologists and a sociologist. The articles were published in 32 different journals, and covered several medical education themes (curriculum, faculty development, educational research methodology, learning methods, assessment, residency education). 22 Attendees answered the evaluation instrument. The MEJC had a positive evaluation from good to excellent, and there was an improvement in self-reported competencies in medical education literature critical appraisal and behaviors related to the use of evidence in educational practice, with a median effect size higher than 0.5. The evaluation instrument had a Cronbach's alpha of 0.96. CONCLUSIONS: A periodic Medical Education Journal Club can improve critical appraisal of the literature, and be maintained long term using evidence-based strategies. This activity is a useful adjunct to the scholarship of teaching. PMID- 26667395 TI - Reduced serum levels of syndecan-1 in patients with tongue squamous cell carcinoma. AB - OBJECTIVES/HYPOTHESIS: To investigate soluble syndecan-1 (Sdc-1) in the sera of patients with tongue squamous cell carcinoma (SCC) and its correlation with the histopathological criteria of tumors. STUDY DESIGN: In a case-control study using a convenient method of sampling, 18 female and 25 male patients with confirmed diagnosis of tongue SCC, and 19 healthy females and 27 males were studied. METHODS: Soluble Sdc-1 was measured in the sera of 43 patients with tongue SCC and was compared with that of healthy age-/sex-matched controls using a commercial enzyme-linked immunosorbent assay. Clinical and pathological data, along with the demographic characteristics of the patients, were recorded at the time of sampling. RESULTS: The levels of soluble Sdc-1 were decreased in the sera of patients compared to controls (91.17 +/- 88.60 vs. 158.17 +/- 103.47 ng/mL, P = .002). Although patients who smoke tended to have higher grades (P = .043), there was no significant difference in the level of syndecan-1 between smokers and non-smokers. A significant difference between syndecan-1 in the sera of patients with tumors of different stages was observed (Kruskal-Wallis test P=0.039); however, scarcity of patients in stages I and III decreased the power of the comparison. CONCLUSIONS: Sdc-1 levels in the sera of patients do not correlate with the tumor progression in the tongue SCC. This is in contrast with the reported inverse correlation between the expression level of membranous Sdc-1 and the histological grade and size of head and neck tumors. Therefore, Sdc-1 shedding may not be a major mechanism in the progressive loss of its expression regarding tongue tumor. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E191-E195, 2016. PMID- 26667396 TI - Treatment of chronic kidney disease using a traditional Chinese medicine, Flos Abelmoschus manihot (Linnaeus) Medicus (Malvaceae). AB - The flowers of Abelmoschus manihot (Linnaeus) Medicus (Malvaceae; Flos A. manihot) have been used in China for many centuries as a traditional Chinese medicine for the treatment of chronic kidney disease. The Huangkui capsule is a single-plant drug extracted from the dry corolla of Flos A. manihot that has been approved by China's State Food and Drug Administration for the treatment of chronic glomerulonephritis. The purpose of this paper is to review briefly some of the past experiences in rapid filtration and to present more fully a few facts brought out in recent studies. The primary chemical constituents of Flos A. manihot are flavonoids. In vivo, the flavonoids can be transformed into glucuronide-sulphate conjugates, which are the major metabolites of Flos A. manihot and could contribute to the renoprotective effects in vivo. Flos A. manihot can ameliorate proteinuria, podocyte apoptosis, glomerulosclerosis and mesangial proliferation. The renoprotective effects of Flos A. manihot are related to inhibition of caspase-3 and caspase-8 overexpression, reduction of the infiltration of ED1(+) and ED3(+) macrophages, downregulation of oxidative stress, inhibition of the p38 mitogen-activated protein kinase and serine/threonine kinase pathways and suppression of transforming growth factor beta1 and tumour necrosis factor-alpha expression. Recently, a multicentre randomized controlled trial demonstrated that Flos A. manihot was more effective than the angiotensin-receptor blocker losartan in reducing proteinuria in patients with primary glomerular disease. Because Flos A. manihot is generally preferred by Chinese patients and clinicians, high-quality trials to test the efficacy and safety of Flos A. manihot are urgently needed. PMID- 26667397 TI - The association of obesity and obesity-related conditions with carotid extra medial thickness in children and adolescents. AB - BACKGROUND: Carotid extra-medial thickness (EMT) and carotid intima-media thickness (cIMT) provide information concerning vascular changes. OBJECTIVES: In this study, we aimed to evaluate the association between carotid EMT and obesity and its metabolic complications in children. METHODS: The study included 38 obese subjects and 30 age-matched and sex-matched healthy controls aged between 7 and 17 years. For all subjects, complete blood count, fasting blood glucose, serum insulin, aspartate aminotransferase, alanine aminotransferase, HDL cholesterol, total cholesterol and triglyceride levels were measured. The carotid EMT and cIMT were measured by an expert radiologist in all patients. RESULTS: Body mass index (BMI) (28.8 +/- 3 vs. 18.1 +/- 2.2, p < 0.001), total cholesterol (167.9 +/- 34.8 mg dL-1 vs. 150.5 +/- 28.1 mg dL-1 , p = 0.029), homeostatic model assessment of insulin resistance (HOMA-IR) (4.3 vs. 1.7, p < 0.001), cIMT (0.51 +/- 0.08 mm vs. 0.45 +/- 0.06 mm, p < 0.001) and carotid EMT (0.74 +/- 0.11 mm vs. 0.64 +/- 0.1 mm, p < 0.001) were significantly higher in obese subjects than in controls, while HDL cholesterol (41.6 +/- 6.5 mg dL-1 vs. 49.5 +/- 7.5 mg dL-1 , p < 0.001) was lower in obesity group. Among the obese subjects, the HOMA-IR values (4.7 vs. 3.6, p = 0.027), cIMT (0.54 +/- 0.07 mm vs. 0.49 +/- 0.07 mm, p = 0.039) and carotid EMT (0.79 +/- 0.1 mm vs. 0.7 +/- 0.1 mm, p = 0.013) were significantly higher in post-pubertal children compared with prepubertal children. BMI, cut-off values of HOMA-IR and cIMT were significantly associated with increased carotid EMT (p < 0.001, p = 0.023 and p < 0.001, respectively). The only independent risk factor affecting carotid EMT was BMI (p < 0.001). CONCLUSION: We have found that carotid EMT is associated with cIMT, obesity and insulin resistance and the assessment of carotid EMT may provide additional information concerning early vascular disease. PMID- 26667398 TI - Peginterferon alpha-2a for the treatment of HIV infection. AB - INTRODUCTION: Novel approaches are urgently needed to achieve the next level of control of HIV infection beyond antiretroviral medications that will lead to the ultimate goal of curing HIV infection. Exploiting the innate immune system control of HIV is one possible component of that strategy with pegylated interferon alpha representing a well-characterized agent that is being applied to this effort. AREAS COVERED: In this review, the authors summarize the history of interferon alpha treatment in the setting of HIV infection with a focus on clinical trials that examined the downstream effects on innate immune responses. More recently, clinical trials that administered pegylated interferon alpha-2a have demonstrated which interferon-stimulated genes are associated with its antiviral effects and which of these host-restriction factors may play a role in limiting the magnitude of the HIV reservoir. EXPERT OPINION: The potential to exploit interferon alpha as part of a cure strategy is provocative. Whether key interferon-induced antiviral factors can be upregulated sufficiently to affect the reservoir is unknown. Additional research employing pegylated interferon alpha-2a is needed to identify which innate immune pathways are candidate targets for novel biological therapies for the potential cure of HIV infection. PMID- 26667399 TI - Benzoindolium-triarylborane conjugates: a ratiometric fluorescent chemodosimeter for the detection of cyanide ions in aqueous medium. AB - Based on benzo[e]indolium and dimesitylborylbenzaldehyde a new ratiometric fluorescent chemodosimeter, C41H43BIN (3) has been synthesized and characterized by (1)H, (13)C NMR spectroscopy, mass spectrometry and single crystal X-ray crystallography. Probe 3 was found to be highly selective and sensitive toward cyanide (CN(-)) ions in aqueous medium even in the presence of other competing anions like F(-), Cl(-), Br(-), I(-), H2PO4(-), HCO3(-) and AcO(-). The detection limit was calculated to be 7.1 * 10(-9) M, which is much lower than the maximum permissable concentration in drinking water (1.9 MUM) set by the World Health Organization (WHO). In addition, the response time of the probe for CN(-) is less than 5 seconds. The mechanism is based on a nucleophilic addition reaction of cyanide ions at the polarized [>C[double bond, length as m-dash]N<](+) bond of the benzoindolium group thereby blocking the pi-conjugation between the benzoindolium and triarylborane moiety. This was further confirmed by (1)H NMR titration, ESI-MS studies and DFT calculations. PMID- 26667401 TI - Aging under Caribbean Skies. PMID- 26667400 TI - A metagenomic approach from aphid's hemolymph sheds light on the potential roles of co-existing endosymbionts. AB - BACKGROUND: Aphids are known to live in symbiosis with specific bacteria, called endosymbionts which can be classified as obligate or accessory. Buchnera aphidicola is generally the only obligatory symbiont present in aphids, supplying essential nutrients that are missing in the plants phloem to its host. Pentalonia nigronervosa is the main vector of the banana bunchy top virus, one of the most damageable viruses in banana. This aphid is carrying two symbionts: B. aphidicola (BPn) and Wolbachia sp. (wPn). The high occurrence of Wolbachia in the banana aphid raises questions about the role it plays in this insect. The goal of this study was to go further in the understanding of the role played by the two symbionts in P. nigronervosa. To do so, microinjection tests were made to see the effect of wPn elimination on the host, and then, high-throughput sequencing of the haemolymph was used to analyze the gene content of the symbionts. RESULTS: We observed that the elimination of wPn systematically led to the death of aphids, suggesting that the bacterium could play a mutualistic role. In addition, we identify and annotate 587 and 250 genes for wPn and BPn, respectively, through high-throughput sequencing. Analysis of these genes suggests that the two bacteria are working together for the production of several essential nutrients. The most striking cases are for lysin and riboflavin which are usually provided by B. aphidicola alone to the host. In the banana aphid, the genes involved in the production pathways of these metabolites are shared between the two bacteria making them both essential for the survival of the aphid host. CONCLUSIONS: Our results suggest that a co-obligatory symbiosis between B. aphidicola and Wolbachia occurs in the banana aphid, the two bacteria acting together to supply essential nutrients to the host. This is, to our knowledge, the first time Wolbachia is reported to play an essential role in aphids. PMID- 26667402 TI - Black Phosphorus Transistors with Near Band Edge Contact Schottky Barrier. AB - Black phosphorus (BP) is a new class of 2D material which holds promise for next generation transistor applications owing to its intrinsically superior carrier mobility properties. Among other issues, achieving good ohmic contacts with low source-drain parasitic resistance in BP field-effect transistors (FET) remains a challenge. For the first time, we report a new contact technology that employs the use of high work function nickel (Ni) and thermal anneal to produce a metal alloy that effectively reduces the contact Schottky barrier height (PhiB) in a BP FET. When annealed at 300 degrees C, the Ni electrode was found to react with the underlying BP crystal and resulted in the formation of nickel-phosphide (Ni2P) alloy. This serves to de-pin the metal Fermi level close to the valence band edge and realizes a record low hole PhiB of merely ~12 meV. The PhiB at the valence band has also been shown to be thickness-dependent, wherein increasing BP multi-layers results in a smaller PhiB due to bandgap energy shrinkage. The integration of hafnium-dioxide high-k gate dielectric additionally enables a significantly improved subthreshold swing (SS ~ 200 mV/dec), surpassing previously reported BP FETs with conventional SiO2 gate dielectric (SS > 1 V/dec). PMID- 26667403 TI - The effects of single-dose dexamethasone on inflammatory response and pain after uterine artery embolisation for symptomatic fibroids or adenomyosis: a randomised controlled study. AB - OBJECTIVE: To investigate the effects of single-dose intravenous dexamethasone on inflammatory responses, pain, nausea, and vomiting after uterine artery embolisation (UAE). DESIGN: Prospective, randomised, double-blind, and placebo controlled study. SETTING: Tertiary-care University centre in Korea. POPULATION: Patients undergoing UAE for the treatment of symptomatic fibroids or adenomyosis. METHODS: Patients were randomised to receive either intravenous dexamethasone (10 mg; dexamethasone group) or normal saline (control group) 1 hour before UAE. Both groups received fentanyl-based intravenous patient-controlled analgesia (PCA) during the 24 hours after UAE. MAIN OUTCOME MEASURES: The primary outcomes were the inflammatory and stress responses measured by white blood cell count, neutrophil percentage, C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol. Secondary outcomes were severity of pain and incidence of nausea and vomiting. RESULTS: Sixty-four patients were enrolled and 59 patients completed the study. CRP, IL-6, and cortisol were significantly lower in the dexamethasone group compared with the control group during the 24 hours after UAE. Although the cumulative dose of fentanyl and additional analgesics administered during the 24 hours after UAE were similar between the two groups, pain scores were significantly lower in the dexamethasone group from 12 hours after UAE, and the incidence of severe nausea and vomiting was lower in the dexamethasone group. CONCLUSIONS: The administration of single-dose intravenous dexamethasone as an adjunct to fentanyl-based intravenous PCA is effective in reducing inflammation and pain during the first 24 hours after UAE. TWEETABLE ABSTRACT: Dexamethasone is effective in reducing inflammation and pain after uterine artery embolisation. PMID- 26667405 TI - SYTAR 2015 Accepted Common Interest Community Proposals. PMID- 26667406 TI - Liver capsule: Cholangiocarcinoma (CCA). PMID- 26667408 TI - New developments at the biointerface. PMID- 26667407 TI - Biosynthesis and Reactivity of Cysteine Persulfides in Signaling. AB - Hydrogen sulfide (H2S) elicits pleiotropic physiological effects ranging from modulation of cardiovascular to CNS functions. A dominant method for transmission of sulfide-based signals is via posttranslational modification of reactive cysteine thiols to persulfides. However, the source of the persulfide donor and whether its relationship to H2S is as a product or precursor is controversial. The transsulfuration pathway enzymes can synthesize cysteine persulfide (Cys-SSH) from cystine and H2S from cysteine and/or homocysteine. Recently, Cys-SSH was proposed as the primary product of the transsulfuration pathway with H2S representing a decomposition product of Cys-SSH. Our detailed kinetic analyses demonstrate a robust capacity for Cys-SSH production by the human transsulfuration pathway enzymes, cystathionine beta-synthase and gamma cystathionase (CSE) and for homocysteine persulfide synthesis from homocystine by CSE only. However, in the reducing cytoplasmic milieu where the concentration of reduced thiols is significantly higher than of disulfides, substrate level regulation favors the synthesis of H2S over persulfides. Mathematical modeling at physiologically relevant hepatic substrate concentrations predicts that H2S rather than Cys-SSH is the primary product of the transsulfuration enzymes with CSE being the dominant producer. The half-life of the metastable Cys-SSH product is short and decomposition leads to a mixture of polysulfides (Cys-S-(S)n-S-Cys). These in vitro data, together with the intrinsic reactivity of Cys-SSH for cysteinyl versus sulfur transfer, are consistent with the absence of an observable increase in protein persulfidation in cells in response to exogenous cystine and evidence for the formation of polysulfides under these conditions. PMID- 26667404 TI - Face repetition detection and social interest: An ERP study in adults with and without Williams syndrome. AB - The present study examined possible neural mechanisms underlying increased social interest in persons with Williams syndrome (WS). Visual event-related potentials (ERPs) during passive viewing were used to compare incidental memory traces for repeated vs. single presentations of previously unfamiliar social (faces) and nonsocial (houses) images in 26 adults with WS and 26 typical adults. Results indicated that participants with WS developed familiarity with the repeated faces and houses (frontal N400 response), but only typical adults evidenced the parietal old/new effect (previously associated with stimulus recollection) for the repeated faces. There was also no evidence of exceptional salience of social information in WS, as ERP markers of memory for repeated faces vs. houses were not significantly different. Thus, while persons with WS exhibit behavioral evidence of increased social interest, their processing of social information in the absence of specific instructions may be relatively superficial. The ERP evidence of face repetition detection in WS was independent of IQ and the earlier perceptual differentiation of social vs. nonsocial stimuli. Large individual differences in ERPs of participants with WS may provide valuable information for understanding the WS phenotype and have relevance for educational and treatment purposes. PMID- 26667409 TI - Retrospective evaluation of the effect of carotid artery stenosis on cerebral oxygen saturation during off-pump coronary artery bypasses grafting in adult patients. AB - BACKGROUND: It is unknown whether cerebral oxygenation in patients with carotid artery stenosis (CAS) undergoing off-pump coronary artery bypass grafting (CABG) differs from that in patients without CAS. Thus, the effect of the presence of CAS >= 50 % on cerebral oxygenation during off-pump CABG in adult patients was evaluated retrospectively. METHODS: Eleven patients with CAS >= 50% and 14 patients without CAS >= 50% were enrolled. Regional cerebral tissue oxygen saturation (rSO2) was quantified using near-infrared spectroscopy. Mean arterial pressure, cardiac index, central venous pressure (CVP), and rSO2 at specific points were collected, and significant changes in each parameter were detected using repeated analysis of variance. Mean rSO2 and minimum rSO2 during anastomosis were analyzed by one-way analysis of variance. Multiple logistic regression analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for cerebral desaturation (a decrease in rSO2 >= 10% from preoperative value). RESULTS: Two patients with CAS >= 50% who received complete carotid artery stenting preoperatively were excluded from the analyses. In both patients with and without CAS, a decrease in rSO2 and cardiac index and an increase in CVP were observed during anastomosis. Mean (SD) maximum decrease in rSO2 from preoperative value was 9.2 (12.7) % on the left side and 8.1 (11.7) % on the right side in patients with CAS >= 50%, and 13.5 (11.3) % on the left side and 16.1 (9.8) % on the right side in patients without CAS >= 50% (p = 0.316). Neurological complications were not identified in both patients with and without CAS >= 50%. In multiple logistic regression analysis, CAS >= 50% was not associated with an increased risk of cerebral desaturation (OR 0.160, 95% CI 0.036-0.707, p = 0.016), and rSO2 decreased with decreasing cardiac index < 2.0 l/min/m(2) (OR 3.287, 95 % CI 2.218-5.076, p < 0.001). CONCLUSIONS: CAS >= 50% was not an independent risk factor of cerebral desaturation during off-pump CABG. Our results suggest that maintaining cardiac output can prevent a decrease in cerebral oxygenation in both patients with and without CAS >= 50%. PMID- 26667410 TI - Passive radiofrequency shimming in the thighs at 3 Tesla using high permittivity materials and body coil receive uniformity correction. AB - PURPOSE: To explore the effects of high permittivity dielectric pads on the transmit and receive characteristics of a 3 Tesla body coil centered at the thighs, and their implications on image uniformity in receive array applications. THEORY AND METHODS: Transmit and receive profiles of the body coil with and without dielectric pads were simulated and measured in healthy volunteers. Parallel imaging was performed using sensitivity encoding (SENSE) with and without pads. An intensity correction filter was constructed from the measured receive profile of the body coil. RESULTS: Measured and simulated data show that the dielectric pads improve the transmit homogeneity of the body coil in the thighs, but decrease its receive homogeneity, which propagates into reconstruction algorithms in which the body coil is used as a reference. However, by correcting for the body coil reception profile this effect can be mitigated. CONCLUSION: Combining high permittivity dielectric pads with an appropriate body coil receive sensitivity filter improves the image uniformity substantially compared with the situation without pads. Magn Reson Med 76:1951-1956, 2016. (c) 2015 International Society for Magnetic Resonance in Medicine. PMID- 26667411 TI - Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development. AB - Dilated cardiomyopathy is a major cause of heart failure (HF) that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and HF in experimental dilated cardiomyopathy. Yet, patients with significant HF unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels, and the stages of HF. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D HF. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B HF and remained low through Stages C and D (P<0.001). Cardiac corin levels were positively correlated with systolic function (r=0.96, P=0.003) and inversely with lung water (r=-0.92, P=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stages C and D) and plasma levels rose only with terminal HF (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate levels (r=0.82, P=0.01 and r=0.8, P=0.02, respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of HF, whereas significant increases in plasma ANP, BNP, and cyclic guanosine monophosphate levels were found only in later stage (C and D) HF. This dyssynchrony in expression of corin versus ANP/BNP may impair cleavage activation of pro natriuretic peptides, and thereby promote the transition from earlier to later stage HF. PMID- 26667412 TI - Human GRK4gamma142V Variant Promotes Angiotensin II Type I Receptor-Mediated Hypertension via Renal Histone Deacetylase Type 1 Inhibition. AB - The influence of a single gene on the pathogenesis of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G-protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4gamma(142V) in mice results in hypertension because of impaired dopamine D1 receptor. Signaling through dopamine D1 receptor and angiotensin II type I receptor (AT1R) reciprocally modulates renal sodium excretion and blood pressure. Here, we demonstrate the ability of the hGRK4gamma(142V) to increase the expression and activity of the AT1R. We show that hGRK4gamma(142V) phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. AT1R blockade and the deletion of the Agtr1a gene normalize the hypertension in hGRK4gamma(142V) mice. These findings illustrate the unique role of GRK4 by targeting receptors with opposite physiological activity for the same goal of maintaining blood pressure homeostasis, and thus making the GRK4 a relevant therapeutic target to control blood pressure. PMID- 26667413 TI - Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake. AB - Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (<100 mEq/d, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic BP (SBP: 8.7+/-1.7 versus -3.0+/-1.5; P=0.013) and diastolic BP (DBP: -5.1+/-0.98 versus 1.4+/-0.94 mm Hg; P<0.05), and the slope of the long-term pressure-natriuresis relationship affected significantly the presence of the lanosterol synthase rs2254524 A variant (AA: 0.71+/-0.22, AC 0.09+/-0.13, and CC 0.04+/-0.11 mEq/mm Hg/24 h; P=0.028). In addition, BP rose in ~25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives. PMID- 26667414 TI - Prediction of Cardiovascular Disease Risk by Cardiac Biomarkers in 2 United Kingdom Cohort Studies: Does Utility Depend on Risk Thresholds For Treatment? AB - We tested the predictive ability of cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, and midregional pro adrenomedullin for cardiovascular disease (CVD) events using the British Regional Heart Study (BRHS) of men aged 60 to 79 years, and the MIDSPAN Family Study (MFS) of men and women aged 30 to 59 years. They included 3757 and 2226 participants, respectively, and during median 13.0 and 17.3 years follow-up the primary CVD event rates were 16.6 and 5.3 per 1000 patient-years, respectively. In Cox models adjusted for basic classical risk factors, 1 SD increases in log-transformed NT proBNP, high-sensitivity troponin T, and midregional pro adrenomedullin were generally associated with increased primary CVD risk in both the studies (P<0.006) except midregional pro adrenomedullin in MFS (P=0.10). In BRHS, QRISK2 risk factors yielded a C-index of 0.657, which was improved by 0.017 (P=0.005) by NT-proBNP, but not by other biomarkers. Using 28% 14-year risk as a proxy for 20% 10-year risk, NT-proBNP improved risk classification for primary CVD cases (case net reclassification index, 5.9%; 95% confidence interval, 2.8%-9.2%), but only improved classification of noncases at a 14% 14-year risk threshold (4.6%; 2.9% 6.3%). In MFS, ASSIGN risk factors yielded a C-index of 0.752 for primary CVD; none of the cardiac biomarkers improved the C-index. Improvements in risk classification were only seen using NT-proBNP and high-sensitivity troponin T among cases using the 28% 14-year risk threshold (4.7%; 1.0%-9.2% and 2.6%; 0.0% 5.8%, respectively). In conclusion, the improvement in treatment allocation gained by adding cardiac biomarkers to risk scores seems to depend on the risk threshold chosen for commencing preventative treatments. PMID- 26667415 TI - Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1-Mediated Protein Kinase A/Uncoupling Protein 2 Pathway. AB - Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE(-/-), ApoE(-/-)/TRPV1(-/-), and ApoE(-/-)/UCP2(-/-) mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE(-/-) mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE(-/-) mice. These effects were not observed in ApoE(-/-) mice lacking the TRPV1 or UCP2 gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease. PMID- 26667416 TI - Genetic Variation in Renal Expression of Folate Receptor 1 (Folr1) Gene Predisposes Spontaneously Hypertensive Rats to Metabolic Syndrome. AB - Metabolism of homocysteine and other sulfur amino acids is closely associated with metabolism of folates. In this study, we analyzed the possible role of folates and sulfur amino acids in the development of features of the metabolic syndrome in the BXH/HXB recombinant inbred strains derived from the spontaneously hypertensive rat (SHR) and Brown Norway progenitors. We mapped a quantitative trait locus for cysteine concentrations to a region of chromosome 1 that contains a cis-acting expression quantitative trait locus regulating mRNA levels of folate receptor 1 (Folr1) in the kidney. Sequence analysis revealed a deletion variant in the Folr1 promoter region of the SHR. Transfection studies demonstrated that the SHR-promoter region of Folr1 is less effective in driving luciferase reporter gene expression than the Brown Norway promoter region of Folr1. Results in the SHR.BN-chr.1 congenic strain confirmed that the SHR variant in Folr1 cosegregates with markedly reduced renal expression of Folr1 and renal folate reabsorption, decreased serum levels of folate, increased serum levels of cysteine and homocysteine, increased adiposity, ectopic fat accumulation in liver and muscle, reduced muscle insulin sensitivity, and increased blood pressure. Transgenic rescue experiments performed by expressing a Folr1 transgene in the SHR ameliorated most of the metabolic disturbances. These findings are consistent with the hypothesis that inherited variation in the expression of Folr1 in the kidney influences the development of the metabolic syndrome and constitutes a previously unrecognized genetic mechanism that may contribute to increased risk for diabetes mellitus and cardiovascular disease. PMID- 26667417 TI - Pregnancy and Long-Term Maternal Cardiovascular Health: Progress Through Harmonization of Research Cohorts and Biobanks. PMID- 26667419 TI - RUMA agrees to restrict the use of colistin. PMID- 26667420 TI - Compulsory testing for BVD to be introduced in Northern Ireland. PMID- 26667421 TI - BCG vaccine shortage: human health agenda must take priority, says BVA. PMID- 26667418 TI - The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. AB - Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies. PMID- 26667422 TI - Defra publishes its first aquatic animal health strategy. PMID- 26667423 TI - Advice on controlled drugs legislation. PMID- 26667424 TI - Veterinary nurse removed from Register for welfare and medicines failings. PMID- 26667425 TI - Canine health screening - making a difference to dogs. PMID- 26667426 TI - New regions of France affected by bluetongue. PMID- 26667427 TI - Way to recognise a successful career. PMID- 26667428 TI - RSPCA calls for tighter controls on the sale of puppies. PMID- 26667429 TI - Making a global impact. AB - How can vets, individually and collectively, make an impact on the global stage? Addressing this question at the BVA Congress at the London Vet Show, Rene Carlson, president of the World Veterinary Association, encouraged the profession to play its part locally, nationally and internationally, in tackling current challenges. Kristy Ebanks reports. PMID- 26667430 TI - Perceptions of professionals and the changing structure of practice. AB - How professionals, such as veterinarians, are perceived by the public, and how they perceive themselves, were among subjects discussed at the recent general assemblies of the Union of European Veterinary Practitioners and the Federation of Veterinarians of Europe. Other matters discussed included antimicrobial resistance and the growth of corporate practice. Karin de Lange reports. PMID- 26667431 TI - Developing a systematic approach to ranking residues of veterinary medicines. AB - This is the last in an occasional series of articles produced for Veterinary Record by the Veterinary Residues Committee(*). It describes a matrix ranking system developed by the committee to provide a systematic approach to ranking residues of veterinary medicines, and some prohibited substances, based on the risk they pose to consumers. PMID- 26667432 TI - Small animal disease surveillance. AB - This is the first UK small animal disease surveillance report from SAVSNET. Future reports will expand to other syndromes and diseases. As data are collected for longer, the estimates of changes in disease burden will become more refined, allowing more targeted local and perhaps national interventions. Anonymised data can be accessed for research purposes by contacting the authors. SAVSNET welcomes feedback on this report. PMID- 26667433 TI - Vaccination against canine parvoviral enteritis in healthy dogs. PMID- 26667434 TI - Correction. PMID- 26667436 TI - Correction. PMID- 26667435 TI - Mycoplasma bovis mastitis in dry dairy cows. PMID- 26667437 TI - Role of Aeromonas hydrophila in CRGV in dogs. PMID- 26667438 TI - Treating hypertension in cats. PMID- 26667439 TI - Anatomical tool available to practices. PMID- 26667440 TI - Centrifuge and hand-held haematocrit meter. PMID- 26667441 TI - New referral facility in London. PMID- 26667442 TI - Answers on canine epilepsy. PMID- 26667443 TI - Environmental treatment for poultry red mite. PMID- 26667444 TI - Soundness in mind and body. AB - Brian McErlean is a vet in Western Australia who lost colleagues to suicide and got involved in a suicide prevention programme. Here he discusses the stresses of the job and the things that make people happy - they may not be what you expect. He also discusses suicide prevention and veterinary support systems being adopted in Australia. PMID- 26667445 TI - CT-based myocardial ischemia evaluation: quantitative angiography, transluminal attenuation gradient, myocardial perfusion, and CT-derived fractional flow reserve. AB - The detection of hemodynamically significant stenosis is important because ischemia-guided revascularization improves overall patient outcomes. Fractional flow reserve (FFR), which is measured during invasive coronary angiography, is regarded as the gold standard for determining hemodynamically significant coronary stenosis. Although coronary computed tomography angiography (CCTA) has been widely used to exclude significant coronary artery disease in patients with low to intermediate pretest probability, anatomic assessment by CCTA using diameter stenosis >=50 % does not correlate well with the functional assessment of FFR. To overcome the weaknesses of conventional CCTA, such as its low specificity and positive predictive value, especially in patients with a small diameter artery, poor image quality, or high calcium score, more sophisticated CCTA analysis methods have been developed to detect hemodynamically significant coronary stenosis. Studies that use the quantification of coronary plaque, transluminal attenuation gradient (TAG), CT myocardial perfusion (CTP), and CT derived FFR have been conducted to validate their diagnostic performances, though each method has its pros and cons. This review provides details on the quantification of coronary plaque, TAG, CTP, and CT-derived FFR, including a definition of each, how to gather and interpret data, and the strengths and limitations of each. Further, we provide an overview of recent clinical studies. PMID- 26667446 TI - Enhanced characterization of calcified areas in intravascular ultrasound virtual histology images by quantification of the acoustic shadow: validation against computed tomography coronary angiography. AB - We enhance intravascular ultrasound virtual histology (VH) tissue characterization by fully automatic quantification of the acoustic shadow behind calcified plaque. VH is unable to characterize atherosclerosis located behind calcifications. In this study, the quantified acoustic shadows are considered calcified to approximate the real dense calcium (DC) plaque volume. In total, 57 patients with 108 coronary lesions were included. A novel post-processing step is applied on the VH images to quantify the acoustic shadow and enhance the VH results. The VH and enhanced VH results are compared to quantitative computed tomography angiography (QTA) plaque characterization as reference standard. The correlation of the plaque types between enhanced VH and QTA differs significantly from the correlation with unenhanced VH. For DC, the correlation improved from 0.733 to 0.818. Instead of an underestimation of DC in VH with a bias of 8.5 mm(3), there was a smaller overestimation of 1.1 mm(3) in the enhanced VH. Although tissue characterization within the acoustic shadow in VH is difficult, the novel algorithm improved the DC tissue characterization. This algorithm contributes to accurate assessment of calcium on VH and could be applied in clinical studies. PMID- 26667447 TI - Cardiac remodelling identified by cardiovascular magnetic resonance in patients with hepatitis C infection and liver disease. AB - Chronic cardiac dysfunction in patients with chronic liver disease (CLD) in the absence of alcohol consumption or other cardiac disease is well described. Whilst functional and morphological features of this condition remain unclear, diastolic dysfunction has been implicated by echocardiography. We aimed to evaluate myocardial structure, function and tissue composition with cardiac magnetic resonance (CMR) imaging in patients with hepatitis C and histological evidence of liver disease on biopsy. Contrast-enhanced CMR imaging for morphological, functional and tissue characterization was performed on 16 patients with CLD and 21 healthy controls. Cardiac structure and function was assessed with standard cine imaging, with Late Gadolinium Enhancement (LGE) and myocardial T1 mapping (pre- and post-contrast) performed to evaluate regional and diffuse myocardial fibrosis respectively. Compared to controls, patients with CLD demonstrated lower left ventricular end-diastolic volume (LVEDV) (138 +/- 36 vs. 167 +/- 44 mL, p < 0.05), reduced stroke volume (88 +/- 20 vs. 109 +/- 29 mL, p = 0.016), lower post contrast myocardial T1 time and higher Partition Coefficient consistent with diffuse myocardial fibrosis (466 +/- 78 vs. 545 +/- 134 ms and 0.247 +/- 0.110 vs. 0.123 +/- 0.057 %, p < 0.05 for both). There were no differences in other cardiac parameters including left ventricular mass and ejection fraction (p = NS for all comparisons). No patients in either group had evidence of LGE. Compared to controls, patients with hepatitis C and histological evidence liver involvement have lower LVEDV, SV and increased diffuse myocardial fibrosis, all of which are associated with diastolic dysfunction. LVEF and LV mass were preserved. This may explain in part previous functional observations made by echocardiography. PMID- 26667448 TI - An analysis of indirect genetic effects on adult body weight of the Pacific white shrimp Litopenaeus vannamei at low rearing density. AB - BACKGROUND: Our aim was to estimate the genetic parameters for the direct genetic effect (DGE) and indirect genetic effects (IGE) on adult body weight in the Pacific white shrimp. IGE is the heritable effect of an individual on the trait values of its group mates. METHODS: To examine IGE on body weight, 4725 shrimp from 105 tagged families were tested in multiple small test groups (MSTG). Each family was separated into three groups (15 shrimp per group) that were randomly assigned to 105 concrete tanks with shrimp from two other families. To estimate breeding values, one large test group (OLTG) in a 300 m(2) circular concrete tank was used for the communal rearing of 8398 individuals from 105 families. Body weight was measured after a growth-test period of more than 200 days. Variance components for body weight in the MSTG programs were estimated using an animal model excluding or including IGE whereas variance components in the OLTG programs were estimated using a conventional animal model that included only DGE. The correlation of DGE between MSTG and OLTG programs was estimated by a two-trait animal model that included or excluded IGE. RESULTS: Heritability estimates for body weight from the conventional animal model in MSTG and OLTG programs were 0.26 +/- 0.13 and 0.40 +/- 0.06, respectively. The log likelihood ratio test revealed significant IGE on body weight. Total heritable variance was the sum of direct genetic variance (43.5%), direct-indirect genetic covariance (2.1%), and indirect genetic variance (54.4%). It represented 73% of the phenotypic variance and was more than two-fold greater than that (32%) obtained by using a classical heritability model for body weight. Correlations of DGE on body weight between MSTG and OLTG programs were intermediate regardless of whether IGE were included or not in the model. CONCLUSIONS: Our results suggest that social interactions contributed to a large part of the heritable variation in body weight. Small and non-significant direct-indirect genetic correlations implied that neutral or slightly cooperative heritable interactions, rather than competition, were dominant in this population but this may be due to the low rearing density. PMID- 26667449 TI - Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. AB - Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability. PMID- 26667450 TI - Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway. AB - Pancreatic cancer is an aggressive malignancy, which generally respond poorly to chemotherapy. Hence, novel agents that are safe and effective are highly needed. The aim of this study was to investigate whether piperlongumine, a natural product isolated from the fruit of the pepper Piper longum, has any efficacy against human pancreatic cancer when used either alone or in combination with gemcitabine in vitro and in a xenograft mouse model. In vitro, piperlongumine inhibited the proliferation of pancreatic cancer cell lines, potentiated the apoptotic effects of gemcitabine, inhibited the constitutive and inducible activation of NF-kappaB, and suppressed the NF-kappaB-regulated expression of c Myc, cyclin D1, Bcl-2, Bcl-xL, Survivin, XIAP, VEGF, and matrix metalloproteinase 9 (MMP-9). Furthermore, in an in vivo xenograft model, we found piperlongumine alone significantly suppressed tumor growth and enhanced the antitumor properties of gemcitabine. These results were consistent with the downregulation of NF kappaB activity and its target genes, decreased proliferation (PCNA and Ki-67), decreased microvessel density (CD31), and increased apoptosis (TUNEL) in tumor remnants. Collectively, our results suggest that piperlongumine alone exhibits significant antitumor effects against human pancreatic cancer and it further enhances the therapeutic effects of gemcitabine, possibly through the modulation of NF-kappaB- and NF-kappaB-regulated gene products. PMID- 26667452 TI - Factors Affecting the Use of Human Tissues in Biomedical Research: Implications in the Design and Operation of a Biorepository. AB - The availability of high-quality human tissues is necessary to advance medical research. Although there are inherent and induced limitations on the use of human tissues in research, biorepositories play critical roles in minimizing the effects of such limitations. Specifically, the optimal utilization of tissues in research requires tissues to be diagnosed accurately, and the actual specimens provided to investigators must be carefully described (i.e., there must be quality control of each aliquot of the tissue provided for research, including a description of any damage to tissues). Tissues also should be collected, processed, stored, and distributed (i.e., handled) uniformly under a rigorous quality management system (QMS). Frequently, tissues are distributed to investigators by tissue banks which have collected, processed, and stored them by standard operating procedures (SOPs). Alternatively, tissues for research may be handled via SOPs that are modified to the specific requirements of investigators (i.e., using a prospective biorepository model). The primary goal of any type of biorepository should be to ensure its specimens are of high quality and are utilized appropriately in research; however, approaches may vary based on the tissues available and requested. For example, extraction of specific molecules (e.g., microRNA) to study molecular characteristics of a tissue may require less clinical annotation than tissues that are utilized to identify how the molecular expression might be used to clarify a clinical outcome of a disease or the response to a specific therapy. This review focuses on the limitations of the use of tissues in research and how the design and operations of a tissue biorepository can minimize some of these limitations. PMID- 26667451 TI - DNA Alkylating Agent Protects Against Spontaneous Hepatocellular Carcinoma Regardless of O6-Methylguanine-DNA Methyltransferase Status. AB - Hepatocellular carcinoma is increasingly important in the United States as the incidence rate rose over the last 30 years. C3HeB/FeJ mice serve as a unique model to study hepatocellular carcinoma tumorigenesis because they mimic human hepatocellular carcinoma with delayed onset, male gender bias, approximately 50% incidence, and susceptibility to tumorigenesis is mediated through multiple genetic loci. Because a human O(6)-methylguanine-DNA methyltransferase (hMGMT) transgene reduces spontaneous tumorigenesis in this model, we hypothesized that hMGMT would also protect from methylation-induced hepatocarcinogenesis. To test this hypothesis, wild-type and hMGMT transgenic C3HeB/FeJ male mice were treated with two monofunctional alkylating agents: diethylnitrosamine (DEN; 0.025 MUmol/g body weight) on day 12 of life with evaluation for glucose-6-phosphatase deficient (G6PD) foci at 16, 24, and 32 weeks or N-methyl-N-nitrosurea (MNU; 25 mg MNU/kg body weight) once monthly for 7 months starting at 3 months of age with evaluation for liver tumors at 12 to 15 months of age. No difference in abundance or size of G6PD foci was measured with DEN treatment. In contrast, it was unexpectedly found that MNU reduces liver tumor prevalence in wild-type and hMGMT transgenic mice despite increased tumor prevalence in other tissues. hMGMT and MNU protections were additive, suggesting that MNU protects through a different mechanism, perhaps through the cytotoxic N7-alkylguanine and N3-alkyladenine lesions which have low mutagenic potential compared with O(6)-alkylguanine lesions. Together, these results suggest that targeting the repair of cytotoxic lesions may be a good preventative for patients at high risk of developing hepatocellular carcinoma. PMID- 26667453 TI - Tissue Microdissection. AB - The new opportunities of modern assays of molecular biology can only be exploited fully if the results can be accurately correlated to the tissue phenotype under investigation. This is a general problem of non-in situ techniques, whereas results from in situ techniques are often difficult to quantify. The use of bulk tissue, which is not precisely characterized in terms of histology, has long been the basis for molecular analysis. It has, however, become apparent, that this simple approach is not sufficient for a detailed analysis of molecular alterations, which might be restricted to a specific tissue phenotype (e.g., tumor or normal tissue, stromal or epithelial cells). Microdissection is a method to provide minute amounts of histologically characterized tissues for molecular analysis with non-in situ techniques and has become an indispensable research tool. If tissue diversity is moderate and negligible, manual microdissection can be an easy and cost-efficient method of choice. In contrast, the advantage of laser microdissection is a very exact selection down to the level of a single cell, but often with a considerable time exposure to get enough material for the following analyses. The latter issue and the method of tissue preparation needed for laser microdissection are the main problems to solve if RNA, highly sensitive to degradation, shall be analyzed. This chapter focuses on optimized procedures for manual microdissection and laser microdissection to analyze RNA of malignant and nonmalignant prostate tissue. PMID- 26667454 TI - Tissue Microarrays. AB - Modern next-generation sequencing and microarray technologies allow for the simultaneous analysis of all human genes on the DNA, RNA, miRNA, and methylation RNA level. Studies using such techniques have lead to the identification of hundreds of genes with a potential role in cancer or other diseases. The validation of all of these candidate genes requires in situ analysis of high numbers of clinical tissues samples. The tissue microarray technology greatly facilitates such analysis. In this method minute tissue samples (typically 0.6 mm in diameter) from up to 1000 different tissues can be analyzed on one microscope glass slide. All in situ methods suitable for histological studies can be applied to TMAs without major changes of protocols, including immunohistochemistry, fluorescence in situ hybridization, or RNA in situ hybridization. Because all tissues are analyzed simultaneously with the same batch of reagents, TMA studies provide an unprecedented degree of standardization, speed, and cost efficiency. PMID- 26667455 TI - Gene Expression Analysis in the Age of Mass Sequencing: An Introduction. AB - During the last years the technology used for gene expression analysis has changed dramatically. The old mainstay, DNA microarray, has served its due course and will soon be replaced by next-generation sequencing (NGS), the Swiss army knife of modern high-throughput nucleic acid-based analysis. Therefore preparation technologies have to adapt to suit the emerging NGS technology platform. Moreover, interpretation of the results is still time consuming and employs the use of high-end computers usually not found in molecular biology laboratories. Alternatively, cloud computing might solve this problem. Nevertheless, these new challenges have to be embraced for gene expression analysis in general. PMID- 26667456 TI - Quantitative DNA Methylation Profiling in Cancer. AB - Epigenetic mechanisms including DNA methylation are fundamental for the regulation of gene expression. Epigenetic alterations can lead to the development and the evolution of malignant tumors as well as the emergence of phenotypically different cancer cells or metastasis from one single tumor cell. Here we describe bisulfite pyrosequencing, a technology to perform quantitative DNA methylation analyses, to detect aberrant DNA methylation in malignant tumors. PMID- 26667457 TI - Single-Nucleotide Polymorphism to Associate Cancer Risk. AB - Genetic heterogeneity explains variation in predisposition for cancer. Whole genome analysis allows risk to be quantified, giving better targeted screening and quantification of the personalized risk posed by environmental factors. Array based approaches to whole-genome analysis are rapidly being overtaken by next generation sequencing (NGS). In this review the different platforms currently available for NGS are compared and the opportunities and risks of this approach are discussed: including the informatics packages required and the ethical issues. Methods applicable to the personal genome machine (PGM) are given as an example of workflows. PMID- 26667458 TI - Exosomes in Cancer Disease. AB - Cancer diagnosis and therapy is steadily improving. Still, diagnosis is frequently late and diagnosis and follow-up procedures mostly are time-consuming and expensive. Searching for tumor-derived exosomes (TEX) in body fluids may provide an alternative, minimally invasive, yet highly reliable diagnostic tool. Beyond this, there is strong evidence that TEX could become a potent therapeutics. Exosomes, small vesicles delivered by many cells of the organism, are found in all body fluids. Exosomes are characterized by lipid composition, common and donor cell specific proteins, mRNA, small non-coding RNA including miRNA and DNA. Particularly the protein and miRNA markers received much attention as they may allow for highly specific diagnosis and can provide hints toward tumor aggressiveness and progression, where exosome-based diagnosis and follow-up is greatly facilitated by the recovery of exosomes in body fluids, particularly the peripheral blood. Beyond this, exosomes are the most important intercellular communicators that modulate, instruct, and reprogram their surrounding as well as distant organs. In concern about TEX this includes message transfer from tumor cells toward the tumor stroma, the premetastatic niche, the hematopoietic system and, last but not least, the instruction of non-cancer stem cells by cancer initiating cells (CIC). Taking this into account, it becomes obvious that "tailored" exosomes offer themselves as potent therapeutic delivery system. In brief, during the last 4-5 years there is an ever-increasing, overwhelming interest in exosome research. This boom appears fully justified provided the content of the exosomes becomes most thoroughly analyzed and their mode of intercellular interaction can be unraveled in detail as this knowledge will open new doors toward cancer diagnosis and therapy including immunotherapy and CIC reprogramming. PMID- 26667459 TI - MicroRNA (miRNA) Profiling. AB - MicroRNAs (miRNAs) are small, highly conserved noncoding RNA molecules involved in the regulation of gene expression. Since each miRNA regulates the expression of hundreds of target mRNAs, miRNAs could function as master coordinators, efficiently regulating fundamental cellular processes, including proliferation, apoptosis, and development. Furthermore, miRNAs may provide useful diagnostic and therapeutic targets in a variety of diseases. However, miRNA expression profiling is essential for the investigation of the biological functions and clinical applications of miRNAs. Therefore, in this chapter, we review and discuss commonly used techniques for miRNAs profiling, as well as their advantages and restrictions. PMID- 26667460 TI - Cancer Gene Profiling for Response Prediction. AB - The revolution of genomic technologies, including gene expression profiling, high resolution mapping of genomic imbalances, and next-generation sequencing, allows us to establish molecular portraits of cancer cells with unprecedented accuracy. This generates hope and justifies anticipation that disease diagnosis, prognosis, and the choice of treatment will be adapted to the individual needs of patients based on molecular evidence. Preoperative treatment strategies are now recommended for a variety of human cancers. Unfortunately, the response of individual tumors to a preoperative treatment is not uniform, and ranges from complete regression to resistance. This poses a considerable clinical dilemma, as patients with a priori resistant tumors could either be spared exposure to radiation or DNA-damaging drugs, i.e., could be referred to primary surgery, or dose-intensified protocols could be pursued. Because the response of an individual tumor as well as therapy-induced side effects represent the major limiting factors of current treatment strategies, identifying molecular markers of response or for treatment toxicity has become exceedingly important. However, complex phenotypes such as tumor responsiveness to multimodal treatments probably do not depend on the expression levels of just one or a few genes and proteins. Therefore, methods that allow comprehensive interrogation of genetic pathways and networks hold great promise in delivering such tumor-specific signatures, since expression levels of thousands of genes can be monitored simultaneously. Over the past few years, microarray technology has emerged as a central tool in addressing pertinent clinical questions, the answers to which are critical for the realization of a personalized genomic medicine, in which patients will be treated based on the biology of their tumor and their genetic profile (Quackenbush, N Engl J Med 354:2463-72, 2006; Jensen et al., Curr Opin Oncol 18:374-380, 2006; Bol and Ebner, Pharmacogenomics 7:227-235, 2006; Nevins and Potti, Nat Rev Genet 8:601-609, 2007). PMID- 26667461 TI - Target Gene Discovery for Novel Therapeutic Agents in Cancer Treatment. AB - Target identification of novel therapeutic drugs is pivotal for the establishment of (1) new anticancer regiments, (2) to control side effects of the drugs, and (3) to identify appropriate combinations with established drugs. Here, we describe several in vitro assays applicable to characterize different characteristics of tumor cells. Furthermore, we present a protocol for establishing a reporter gene system for in vivo imaging, allowing for the study of drug effects in small animal models. PMID- 26667462 TI - Application of Proteomics in Cancer Biomarker Discovery: GeLC-MS/MS. AB - Proteomic approaches are being increasingly applied to study multiple facets of healthy and diseased processes. In particular, the application of global proteome profiling in the field of oncology is already starting to shape the diagnostic, prognostic, monitoring, and therapeutic approaches. At the heart of such approaches lies a quest for clinically relevant biomarkers, particularly arising from global analyses of body fluids, as, in major part, they represent easily accessible and noninvasive matrices. A detailed protocol of one of the popular approaches for global proteome profiling, SDS-PAGE-liquid chromatography-tandem mass spectrometry or GeLC-MS/MS, and its application for biomarker discovery in urine is provided here. PMID- 26667463 TI - Meta-analysis of Cancer Gene Profiling Data. AB - The simultaneous measurement of thousands of genes gives the opportunity to personalize and improve cancer therapy. In addition, the integration of meta-data such as protein-protein interaction (PPI) information into the analyses helps in the identification and prioritization of genes from these screens. Here, we describe a computational approach that identifies genes prognostic for outcome by combining gene profiling data from any source with a network of known relationships between genes. PMID- 26667464 TI - Reproducible, Scalable Fusion Gene Detection from RNA-Seq. AB - Chromosomal rearrangements resulting in the creation of novel gene products, termed fusion genes, have been identified as driving events in the development of multiple types of cancer. As these gene products typically do not exist in normal cells, they represent valuable prognostic and therapeutic targets. Advances in next-generation sequencing and computational approaches have greatly improved our ability to detect and identify fusion genes. Nevertheless, these approaches require significant computational resources. Here we describe an approach which leverages cloud computing technologies to perform fusion gene detection from RNA sequencing data at any scale. We additionally highlight methods to enhance reproducibility of bioinformatics analyses which may be applied to any next generation sequencing experiment. PMID- 26667465 TI - Transcriptome Sequencing for the Detection of Chimeric Transcripts. AB - The occurrence of chimeric transcripts has been reported in many cancer cells and seen as potential biomarkers and therapeutic targets. Modern high-throughput sequencing technologies offer a way to investigate individual chimeric transcripts and the systematic information of associated gene expressions about underlying genome structural variations and genomic interactions. The detection methods of finding chimeric transcripts from massive amount of short read sequence data are discussed here. Both assembly-based and alignment-based methods are used for the investigation of chimeric transcripts. PMID- 26667466 TI - Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats. AB - In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl4)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl4-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl4-induced increases in inflammatory mediators, including tumor necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-kappaB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone showed antioxidative and anti-inflammatory effects in CCl4 intoxicated rats by inhibiting oxidative stress and NF-kappaB activation via blockade of the activation of upstream MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis. PMID- 26667467 TI - The institutional response to mental disorder in Ireland: censuses of Irish asylums, psychiatric hospitals and units 1844-2014. AB - Before the eighteenth century, there was limited response to the problem of psychiatric illness in Ireland as in many other countries. The asylums of the 1820s and 1830s were no sooner opened than they were overcrowded. A second wave of asylum building commenced in the second half of the nineteenth century continuing up to the early twentieth century. In 1966, the Report of the Commission on Mental Illness noted that the rate of psychiatric beds in Ireland per 1,000 was one of the highest in the world. The report called for a change in the policy of caring for the mentally ill in psychiatric hospitals to more community-based settings and in psychiatric units located in general hospital settings, along with a call for more research into mental illness. The result of the latter was the establishment of the first census of psychiatric patients resident in psychiatric hospitals. Thus began fifty years of census reporting and the subsequent establishment of the National Psychiatric Inpatient Reporting System (NPIRS). PMID- 26667468 TI - Non-invasive measuring of the acceleration of contraction of the left ventricle with the Doppler echocardiography. AB - BACKGROUND: Echocardiographically measured ejection fraction (EF) of the left ventricle (LV) is the most useful standard of the LV systolic function. Its limitations are poor delineation of the LV endocardium, pronounced regional disorders of contractility, dyssynchrony of the LV and in particular significant mitral regurgitation. The aim of this research is to evaluate the advantage of Doppler indices of left ventricular function such as index of acceleration of contraction of the LV (AccLV) over EF in patients with heart failure. METHODS: We performed a prospective observational study. We included 45 patients with known chronic heart failure and 76 healthy subjects. We performed standard echocardiographic measurements. AccLV was calculated by the following formula: AccLV = Vmax LVOT/dt * EDV [cm/s(2) ml]. Vmax LVOT represents the maximum velocity during ejection in the left ventricular outflow tract (LVOT), dt stands for the interval from the beginning of the LV contraction to the achieved Vmax LVOT, EDV represents end-diastolic volume of the LV. RESULTS: Between patients and healthy subjects we observed statistically significant differences in mean EF values (65.4 +/- 6.7 % vs. 38.6 +/- 18.0 %; p < 0.001) and of AccLV (12.1 +/- 2.88 cm/s(2)ml vs. 4.4 +/- 2.1 cm/s(2)ml; p < 0.001). Receiver operating characteristic (ROC) curve showed higher area under the curve values for AccLV in comparison to EF (0.996 vs. 0.897). In the patient group we observed more important correlation between AccLV index and the New York Heart Association (NYHA) functional classes (r = - 0.657; p < 0.001), than between EF and the NYHA classes (r = - 0.539; p < 0.001). CONCLUSIONS: We could distinguish with higher accuracy between healthy subjects and patients with heart failure LV by calculated AccLV in comparison to EF. AccLV values correlated with NYHA functional classes in patients with heart failure better than EF values. PMID- 26667469 TI - Authors' reply to Yamana and colleagues. PMID- 26667470 TI - Competition dependence of retrieval-induced forgetting in motor memory. AB - In two experiments, we examined the competition dependence of retrieval-induced forgetting (RIF) in motor memory. Participants learned sequential finger movements as responses to letter stimuli. The learning phase comprised two parts. In both parts, half of the motor sequences were to be executed at one of two locations (the left or right side of a keyboard) by pressing the corresponding response keys. Retrieval practice of half of the motor sequences at one location induced forgetting of the nonpracticed motor sequences at that location. However, RIF was prevented in Experiment 1 when retrieval practice took place before the nonpracticed items had even been encoded. In Experiment 2, RIF was prevented by intentionally forgetting the nonpracticed motor sequences prior to retrieval practice. These results suggest that precluding competition by related items during retrieval practice precluded them from being affected by RIF. The present findings support an inhibitory account and speak against the alternative assumptions that associative blocking or a mental context change causes RIF. PMID- 26667471 TI - Can physicochemical properties of antimicrobials be used to predict their pharmacokinetics during extracorporeal membrane oxygenation? Illustrative data from ovine models. AB - INTRODUCTION: Ex vivo experiments in extracorporeal membrane oxygenation (ECMO) circuits have identified octanol-water partition coefficient (logP, a marker of lipophilicity) and protein binding (PB) as key drug factors affecting pharmacokinetics (PK) during ECMO. Using ovine models, in this study we investigated whether these drug properties can be used to predict PK alterations of antimicrobial drugs during ECMO. METHODS: Single-dose PK sampling was performed in healthy sheep (HS, n = 7), healthy sheep on ECMO (E24H, n = 7) and sheep with smoke inhalation acute lung injury on ECMO (SE24H, n = 6). The sheep received eight study antimicrobials (ceftriaxone, gentamicin, meropenem, vancomycin, doripenem, ciprofloxacin, fluconazole, caspofungin) that exhibit varying degrees of logP and PB. Plasma drug concentrations were determined using validated chromatographic techniques. PK data obtained from a non-compartmental analysis were used in a linear regression model to predict PK parameters based on logP and PB. RESULTS: We found statistically significant differences in pH, haemodynamics, fluid balance and plasma proteins between the E24H and SE24H groups (p < 0.001). logP had a strong positive linear relationship with steady state volume of distribution (Vss) in both the E24H and SE24H groups (p < 0.001) but not in the HS group (p = 0.9) and no relationship with clearance (CL) in all study groups. Although we observed an increase in CL for highly PB drugs in ECMO sheep, PB exhibited a weaker negative linear relationship with both CL (HS, p = 0.01; E24H, p < 0.001; SE24H, p < 0.001) and Vss (HS, p = 0.01; E24H, p = 0.004; SE24H, p = 0.05) in the final model. CONCLUSIONS: Lipophilic antimicrobials are likely to have an increased Vss and decreased CL during ECMO. Protein-bound antimicrobial agents are likely to have reductions both in CL and Vss during ECMO. The strong relationship between lipophilicity and Vss seen in both the E24H and SE24H groups indicates circuit sequestration of lipophilic drugs. These findings highlight the importance of drug factors in predicting antimicrobial drug PK during ECMO and should be a consideration when performing and interpreting population PK studies. PMID- 26667472 TI - Risk assessment of gene flow from genetically engineered virus resistant cassava to wild relatives in Africa: an expert panel report. AB - The probability and consequences of gene flow to wild relatives is typically considered in the environmental risk assessment of genetically engineered crops. This is a report from a discussion by a group of experts who used a problem formulation approach to consider existing information for risk assessment of gene flow from cassava (Manihot esculenta) genetically engineered for virus resistance to the 'wild' (naturalized) relative M. glaziovii in East Africa. Two environmental harms were considered in this case: (1) loss of genetic diversity in the germplasm pool, and (2) loss of valued species, ecosystem resources, or crop yield and quality due to weediness or invasiveness of wild relatives. Based on existing information, it was concluded that gene flow will occur, but it is not likely that this will reduce the genetic diversity in the germplasm pool. There is little existing information about the impact of the virus in natural populations that could be used to inform a prediction about whether virus resistance would lead to an increase in reproduction or survival, hence abundance of M. glaziovii. However, an increase in the abundance of M. glaziovii should be manageable, and would not necessarily lead to the identified environmental harms. PMID- 26667474 TI - Reg3g overexpression promotes beta cell regeneration and induces immune tolerance in nonobese-diabetic mouse model. AB - The regenerating islet-derived gene was first isolated in regenerated pancreas tissues, greatly contributing to beta cell regeneration. It is an anti inflammatory in response to cellular stress. This encouraged us to investigate the exact role of a novel member of Reg family, regenerating islet-derived gene gamma, in type 1 diabetes of nonobese-diabetic mice. For this, Reg3g gene was overexpressed in pancreatic islets, and conferred beneficial effects on beta cell regeneration through activating the Janus kinase 2/signal transducer and activator of transcription 3/nuclear factor kappaB signaling pathway. Lentiviral vector-encoding regenerating islet-derived gene gamma treatment also decreased lymphocyte infiltrates of the intra-islet and peri-islet by inducing both differentiation of regulatory T cell and immature dendritic cells of tolerogenic properties, which attenuated autoimmunity. This treatment further contributed to rebalanced levels of type 1/2 helper T cell cytokines and elevated alpha1 antitrypsin levels in the serum. These results were not observed in phosphate buffered saline-treated mice or in lentivirus-control mice. We have shown, for the first time, to our knowledge, that regenerating islet-derived gene gamma promotes beta cell regeneration and preserves beta cells from autoimmunity damage by increasing regulatory T cell differentiation and inducing tolerated dendritic cells. This regenerating islet-derived gene gamma infusion could probably be developed into an optimal gene therapy for the prevention and reversal of type 1 diabetes. PMID- 26667473 TI - Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region. AB - Monocytes and monocyte-derived macrophages express relatively low levels of CD4. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission; however, the mechanism or mechanisms of virus infection are poorly understood. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Human immunodeficiency virus type 1 infection of monocyte-derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin like lectin-1. The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor-derived monocyte-derived macrophages was significantly greater than on granulocyte macrophage colony stimulating factor-derived monocyte-derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor-derived monocyte-derived macrophages. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1 interaction with sialic acid-binding immunoglobulin like lectin and entry into macrophage colony-stimulating factor-derived monocyte derived macrophages. Removal of sialic acid residues or glycans from scaffolded V1V2 protein decreased human immunodeficiency virus type 1 infectivity. These results highlight the importance of sialic acids on the V1V2 region in binding to sialic acid-binding immunoglobulin-like lectin and suggest that the unusually long surface-exposed sialic acid-binding immunoglobulin-like lectin might aid in the capture and entry of human immunodeficiency virus type 1 into monocyte derived macrophages. PMID- 26667475 TI - Building-related health impacts in European and Chinese cities: a scalable assessment method. AB - BACKGROUND: Public health is often affected by societal decisions that are not primarily about health. Climate change mitigation requires intensive actions to minimise greenhouse gas emissions in the future. Many of these actions take place in cities due to their traffic, buildings, and energy consumption. Active climate mitigation policies will also, aside of their long term global impacts, have short term local impacts, both positive and negative, on public health. Our main objective was to develop a generic open impact model to estimate health impacts of emissions due to heat and power consumption of buildings. In addition, the model should be usable for policy comparisons by non-health experts on city level with city-specific data, it should give guidance on the particular climate mitigation questions but at the same time increase understanding on the related health impacts and the model should follow the building stock in time, make comparisons between scenarios, propagate uncertainties, and scale to different levels of detail. We tested The functionalities of the model in two case cities, namely Kuopio and Basel. We estimated the health and climate impacts of two actual policies planned or implemented in the cities. The assessed policies were replacement of peat with wood chips in co-generation of district heat and power, and improved energy efficiency of buildings achieved by renovations. RESULTS: Health impacts were not large in the two cities, but also clear differences in implementation and predictability between the two tested policies were seen. Renovation policies can improve the energy efficiency of buildings and reduce greenhouse gas emissions significantly, but this requires systematic policy sustained for decades. In contrast, fuel changes in large district heating facilities may have rapid and large impacts on emissions. However, the life cycle impacts of different fuels is somewhat an open question. CONCLUSIONS: In conclusion, we were able to develop a practical model for city-level assessments promoting evidence-based policy in general and health aspects in particular. Although all data and code is freely available, implementation of the current model version in a new city requires some modelling skills. PMID- 26667476 TI - Fluorescence-Enhanced Sensing of Hypochlorous Acid Based on 2-Pyridylthiazole Unit. AB - Hypochlorous acid, being one of reactive oxygen species (ROS), is essential to protect the body against invasion of pathogens. Excess of hypochlorous acid (HOCl) is believed to be in tight connection with various inflammation-related diseases. It remains a challenge to detect the ROS in physiological conditions (aqueous buffer and neutral pH) with selectivity. In the presented paper, we have synthesized a ferrocence-modified pyridylthiazole derivatives, 1,4-di{5-[(4' ferrocenyl-2'-(4"-pyridyl)]thiazinyl}benzene (DFPT). Only HOCl could turn-on the fluorescence of DFPT with enhanced emission at 465 nm. Compared to the other reported HOCl sensors, DFPT could selectively detect HOCl with rapid response (< 60 s) in the aqueous buffer (pH = 7.0). The detection limit at pH = 7.0 was 0.7 MUM according to the titration experiment. PMID- 26667477 TI - Reducing Prejudice With Labels: Shared Group Memberships Attenuate Implicit Bias and Expand Implicit Group Boundaries. AB - In three experiments, we used a novel Implicit Association Test procedure to investigate the impact of group memberships on implicit bias and implicit group boundaries. Results from Experiment 1 indicated that categorizing targets using a shared category reduced implicit bias by increasing the extent to which positivity was associated with Blacks. Results from Experiment 2 revealed that shared group membership, but not mere positivity of a group membership, was necessary to reduce implicit bias. Quadruple process model analyses indicated that changes in implicit bias caused by shared group membership are due to changes in the way that targets are evaluated, not to changes in the regulation of evaluative bias. Results from Experiment 3 showed that categorizing Black targets into shared group memberships expanded implicit group boundaries. PMID- 26667478 TI - The effects of cognitive reappraisal following retrieval-procedures designed to destabilize alcohol memories in high-risk drinkers. AB - RATIONALE: Addiction is a disorder of motivational learning and memory. Maladaptive motivational memories linking drug-associated stimuli to drug seeking are formed over hundreds of reinforcement trials and accompanied by aberrant neuroadaptation in the mesocorticolimbic reward system. Such memories are resistant to extinction. However, the discovery of retrieval-dependent memory plasticity has opened up the possibility of permanent modification of established (long-term) memories during 'reconsolidation'. OBJECTIVES: Here, we investigate whether reappraisal of maladaptive alcohol cognitions performed after procedures designed to destabilize alcohol memory networks affected subsequent alcohol memory, craving, drinking and attentional bias. METHODS: Forty-seven at-risk drinkers attended two sessions. On the first lab session, participants underwent one of two prediction error-generating procedures in which outcome expectancies were violated while retrieving alcohol memories (omission and value prediction error groups). Participants in a control group retrieved non-alcohol memories. Participants then reappraised personally relevant maladaptive alcohol memories and completed measures of reappraisal recall, alcohol verbal fluency and craving. Seven days later, they repeated these measures along with attentional bias assessment. RESULTS: Omission prediction error (being unexpectedly prevented from drinking beer), but not a value prediction error (drinking unexpectedly bitter tasting beer) or control procedure (drinking unexpectedly bitter orange juice), was associated with significant reductions in verbal fluency for positive alcohol related words. No other statistically robust outcomes were detected. CONCLUSIONS: This study provides partial preliminary support for the idea that a common psychotherapeutic strategy used in the context of putative memory retrieval destabilization can alter accessibility of alcohol semantic networks. Further research delineating the necessary and sufficient requirements for producing alterations in alcohol memory performance based on memory destabilization is still required. PMID- 26667480 TI - The effectiveness of low-level laser therapy for nonspecific chronic low back pain: a systematic review and meta-analysis. AB - BACKGROUND: In recent decades, low-level laser therapy (LLLT) has been widely used to relieve pain caused by different musculoskeletal disorders. Though widely used, its reported therapeutic outcomes are varied and conflicting. Results similarly conflict regarding its usage in patients with nonspecific chronic low back pain (NSCLBP). This study investigated the efficacy of low-level laser therapy (LLLT) for the treatment of NSCLBP by a systematic literature search with meta-analyses on selected studies. METHOD: MEDLINE, EMBASE, ISI Web of Science and Cochrane Library were systematically searched from January 2000 to November 2014. Included studies were randomized controlled trials (RCTs) written in English that compared LLLT with placebo treatment in NSCLBP patients. The efficacy effect size was estimated by the weighted mean difference (WMD). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)). RESULTS: Of 221 studies, seven RCTs (one triple blind, four double-blind, one single-blind, one not mentioning blinding, totaling 394 patients) met the criteria for inclusion. Based on five studies, the WMD in visual analog scale (VAS) pain outcome score after treatment was significantly lower in the LLLT group compared with placebo (WMD = -13.57 [95 % CI = -17.42, 9.72], I(2) = 0 %). No significant treatment effect was identified for disability scores or spinal range of motion outcomes. CONCLUSIONS: Our findings indicate that LLLT is an effective method for relieving pain in NSCLBP patients. However, there is still a lack of evidence supporting its effect on function. PMID- 26667481 TI - Perspectives of Japanese oncologists on the health economics of innovative cancer treatments. AB - BACKGROUND: Few reports have thus far discussed the influence of economic factors on treatment decision-making by patients. The objective of the present study was to clarify the awareness among oncologists of health economics in cancer treatment. METHODS: The present study was based on the questionnaire regarding health economics in cancer treatment carried out by the Japan Society of Clinical Oncology (JSCO) in July 2013. The subjects were trustees registered with JSCO. The survey investigated the influence of medical expenses on patient access to and selection of medical treatment in order to clarify the primary attributes of the respondents and their awareness of economics. The study also investigated the maximum allowable public medical expenses to prolong the life expectancy of a cancer patient by 1 year and the factors that can influence treatment selection. RESULTS: The 172 respondents had completed a mean of 30.3 +/- 6.2 postgraduate years, and the mean number of patients they treated annually was 1323 +/- 1963. The degree of treatment accessibility among patients was perceived positively by 112 (71.3 %) and negatively by 49 (28.7 %) of the respondents, irrespective of medical expenses. Of the 172 respondents, 66 (41.0 %) believed that the maximum allowable medical expenses for cancer treatment should be <=4 million yen/LY, with 62 (39.8 %) reporting a value of 4.01-8 million yen/LY. CONCLUSION: The findings of this study suggest that a certain range of medical expenses has come to be regarded as the standard range of medical expenses for cancer treatment among oncologists, with answers based on the premise that patients should have access to effective medical treatment. PMID- 26667479 TI - Autoantibodies to central nervous system neuronal surface antigens: psychiatric symptoms and psychopharmacological implications. AB - RATIONALE: Autoantibodies to central nervous system (CNS) neuronal surface antigens have been described in association with autoimmune encephalopathies which prominently feature psychiatric symptoms in addition to neurological symptoms. The potential role of these autoantibodies in primary psychiatric diseases such as schizophrenia or bipolar affective disorder is of increasing interest. OBJECTIVES: We aimed to review the nature of psychiatric symptoms associated with neuronal surface autoantibodies, in the context of autoimmune encephalopathies as well as primary psychiatric disorders, and to review the mechanisms of action of these autoantibodies from a psychopharmacological perspective. RESULTS: The functional effects of the autoantibodies on their target antigens are described; their clinical expression is at least in part mediated by their effects on neuronal receptor function, primarily at the synapse, usually resulting in receptor hypofunction. The psychiatric effects of the antibodies are related to known functions of the receptor target or its complexed proteins, with reference to supportive genetic and pharmacological evidence where relevant. Evidence for a causal role of these autoantibodies in primary psychiatric disease is increasing but remains controversial; relevant methodological controversies are outlined. Non-receptor-based mechanisms of autoantibody action, including neuroinflammatory mechanisms, and therapeutic implications are discussed. CONCLUSIONS: An analysis of the autoantibodies from a psychopharmacological perspective, as endogenous, bioactive, highly specific, receptor-targeting molecules, provides a valuable opportunity to understand the neurobiological basis of associated psychiatric symptoms. Potentially, new treatment strategies will emerge from the improving understanding of antibody antigen interaction within the CNS. PMID- 26667482 TI - Exposure to BTEX and Ethers in Petrol Station Attendants and Proposal of Biological Exposure Equivalents for Urinary Benzene and MTBE. AB - OBJECTIVE: To assess exposure to benzene (BEN) and other aromatic compounds (toluene, ethylbenzene, m+p-xylene, o-xylene) (BTEX), methyl tert-butyl ether (MTBE), and ethyl tert-butyl ether (ETBE) in petrol station workers using air sampling and biological monitoring and to propose biological equivalents to occupational limit values. METHODS: Eighty-nine petrol station workers and 90 control subjects were investigated. Personal exposure to airborne BTEX and ethers was assessed during a mid-week shift; urine samples were collected at the beginning of the work week, prior to and at the end of air sampling. RESULTS: Petrol station workers had median airborne exposures to benzene and MTBE of 59 and 408 ug m(-3), respectively, with urinary benzene (BEN-U) and MTBE (MTBE-U) of 339 and 780 ng l(-1), respectively. Concentrations in petrol station workers were higher than in control subjects. There were significant positive correlations between airborne exposure and the corresponding biological marker, with Pearson's correlation coefficient (r) values of 0.437 and 0.865 for benzene and MTBE, respectively. There was also a strong correlation between airborne benzene and urinary MTBE (r = 0.835). Multiple linear regression analysis showed that the urinary levels of benzene were influenced by personal airborne exposure, urinary creatinine, and tobacco smoking [determination coefficient (R(2)) 0.572], while MTBE-U was influenced only by personal exposure (R(2) = 0.741). CONCLUSIONS: BEN U and MTBE-U are sensitive and specific biomarkers of low occupational exposures. We propose using BEN-U as biomarker of exposure to benzene in nonsmokers and suggest 1457 ng l(-1) in end shift urine samples as biological exposure equivalent to the EU occupational limit value of 1 p.p.m.; for both smokers and nonsmokers, MTBE-U may be proposed as a surrogate biomarker of benzene exposure, with a biological exposure equivalent of 22 ug l(-1) in end shift samples. For MTBE exposure, we suggest the use of MTBE-U with a biological exposure equivalent of 22 ug l(-1) corresponding to the occupational limit value of 50 p.p.m. PMID- 26667484 TI - Problem-based learning in resource-poor settings: lessons from a medical school in Ghana. AB - Problem-based learning (PBL) is arguably one of the most important innovations in medical education in the last century. The evident benefits of PBL and the changing face of medicine and medical education have led many institutions including those in resource-poor settings to consider the adoption of PBL curricula. However, experts are uncertain about how successful PBL will be in such settings, as literature on the implementation of PBL in resource-poor settings appears to be inadequate. The University of Cape Coast is located in a resource-poor setting, however, its medical school has used PBL curriculum since 2007. In a descriptive prose, this article discusses the PBL implementation processes, the challenges faced, the mitigation strategies employed, and the lessons learned at University of Cape Coast School of Medical Sciences (UCCSMS). The arguments fall under the broad themes of curricular structure, resource constraints, faculty development, and assessment. The peculiar socioeconomic situation of Ghana, challenges in funding of tertiary education, and the resource implications of PBL provided the context for the arguments. It emerged out of the discussion that PBL has to be implemented as whole curriculum to be effective. Regular faculty development activities on PBL and the alignment of assessment methods with PBL also emerged as important issues in the discussion. The article argues that in spite of its cost implication, a PBL curriculum can be successfully implemented in resource-constrained settings. PMID- 26667485 TI - A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non-Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib. AB - PURPOSE: In this phase Ib/II study, we aimed to assess the safety and efficacy of afatinib plus nimotuzumab (N) in advanced non-small cell lung cancer (NSCLC) patients with acquired resistance to gefitinib or erlotinib. EXPERIMENTAL DESIGN: In phase Ib stage, patients received afatinib (40 mg or 30 mg once daily) plus nimotuzumab (100 mg or 200 mg once weekly) for 28-day cycles to determine the recommended phase II dose (RPIID). The safety and efficacy of RPIID dose was evaluated in phase II stage. RESULTS: In total, 50 patients were enrolled (13 to phase Ib and 37 to phase II). In the first dose-finding cohort (afatinib 40 mg plus nimotuzumab 100 mg), one patient experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and in the subsequent cohort (afatinib 40 mg plus nimotuzumab 200 mg), two DLTs (grade 3 diarrhea and grade 3 neutropenia) occurred in 2 of 6 patients. Accordingly, RPIID was determined as afatinib 40 mg plus nimotuzumab 100 mg. In 44 patients treated with RPIID, 7 (16%) patients had grade 3 toxicities; skin rash (7%), diarrhea (5%), acne (2%), and fatigue (2%). The overall response rate was 23% and the median duration of response was 4.3 months (range, 0.7-16.2 months). The median progression-free survival and overall survival were 4.0 months [95% confidence interval (CI), 2.3-5.7 months] and 11.7 months (95% CI, 9.4-14.0 months), respectively. CONCLUSIONS: Combination treatment of afatinib and nimotuzumab demonstrated an acceptable safety profile and encouraging antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib. Larger phase III trial is warranted to confirm its efficacy and safety. Clin Cancer Res; 22(9); 2139-45. (c)2015 AACR. PMID- 26667483 TI - Phosphorylation of murine SAMHD1 regulates its antiretroviral activity. AB - BACKGROUND: Human SAMHD1 is a triphosphohydrolase that restricts the replication of retroviruses, retroelements and DNA viruses in noncycling cells. While modes of action have been extensively described for human SAMHD1, only little is known about the regulation of SAMHD1 in the mouse. Here, we characterize the antiviral activity of murine SAMHD1 with the help of knockout mice to shed light on the regulation and the mechanism of the SAMHD1 restriction and to validate the SAMHD1 knockout mouse model for the use in future infectivity studies. RESULTS: We found that endogenous mouse SAMHD1 restricts not only HIV-1 but also MLV reporter virus infection at the level of reverse transcription in primary myeloid cells. Similar to the human protein, the antiviral activity of murine SAMHD1 is regulated through phosphorylation at threonine 603 and is limited to nondividing cells. Comparing the susceptibility to infection with intracellular dNTP levels and SAMHD1 phosphorylation in different cell types shows that both functions are important determinants of the antiviral activity of murine SAMHD1. In contrast, we found the proposed RNase activity of SAMHD1 to be less important and could not detect any effect of mouse or human SAMHD1 on the level of incoming viral RNA. CONCLUSION: Our findings show that SAMHD1 in the mouse blocks retroviral infection at the level of reverse transcription and is regulated through cell cycle-dependent phosphorylation. We show that the antiviral restriction mediated by murine SAMHD1 is mechanistically similar to what is known for the human protein, making the SAMHD1 knockout mouse model a valuable tool to characterize the influence of SAMHD1 on the replication of different viruses in vivo. PMID- 26667486 TI - ICAM-1-Related Noncoding RNA in Cancer Stem Cells Maintains ICAM-1 Expression in Hepatocellular Carcinoma. AB - PURPOSE: Portal vein tumor thrombus (PVTT) is a major complication of hepatocellular carcinoma (HCC) and is associated with poor survival. Long noncoding RNAs (lncRNA) contribute to HCC metastasis, but whether and how lncRNAs affect PVTT development remains unclear. In the present study, a novel highly expressed lncRNA (ICAM-1-related, ICR) was identified in ICAM-1(+)cancer stem cells (CSC) in HCC. This lncRNA regulated CSC properties and contributed to PVTT development. EXPERIMENTAL DESIGN: We used microarray and bioinformatics analyses to identify differentially expressed lncRNAs. Real-time PCR and Western blotting were used to assess gene expression in cell lines and tumors. Sphere formation assays were performed to investigate stem cell properties of tumor cellsin vitro Retrospective and prospective studies were used to investigate the relationship between ICR expression and clinical outcomes. RESULTS: Compared with the corresponding primary tumors, PVTT expressed different lncRNAs and mRNAs, including the upregulated lncRNA ICR and ICAM-1. ICR regulated ICAM-1 expression by increasing the stability of its mRNA through RNA duplex formation, which modulated the CSC properties of ICAM-1(+)HCC cells. ICR transcription in ICAM 1(+)HCC cells was regulated by Nanog, and inhibition of ICRin situsignificantly reduced ICAM-1 expression and ICAM-1(+)HCC cells in tumorsin vivo Moreover, elevated ICR and ICAM-1 expression in tumors was correlated with PVTT development and poor clinical outcomes. CONCLUSIONS: Our study demonstrates that ICR specifically regulates CSC properties of ICAM-1(+)HCC cells and that ICR contributes to PVTT development. Therefore, ICR may be a promising target for HCC therapy. PMID- 26667488 TI - Enumeration and Molecular Characterization of Tumor Cells in Lung Cancer Patients Using a Novel In Vivo Device for Capturing Circulating Tumor Cells. AB - PURPOSE: The use of circulating tumor cells (CTC) as "liquid biopsy" is limited by the very low yield of CTCs available for subsequent analyses. Most in vitro approaches rely on small sample volumes (5-10 mL). EXPERIMENTAL DESIGN: Here, we used a novel approach, the GILUPI CellCollector, which enables an in vivo isolation of CTCs from peripheral blood. In total, 50 lung cancer patients were screened in two subsequent device applications before and after therapy (n = 185 applications). RESULTS: By in vivo isolation, 58% (108/185) of the patients were positive for >=1 CTC (median, 5 CTCs; range, 1-56 cells) as compared with 27% (23/84; range, 1-300 cells) using the FDA-cleared CellSearch system. Furthermore, we could show that treatment response during therapy was associated with significant decreases in CTC counts (P = 0.001). By dPCR, mutations in the KRAS and EGFR genes relevant for treatment decisions could be detected in CTCs captured by in vivo isolation and confirmed in the primary tumors of the same patients. CONCLUSIONS: In vivo isolation of CTCs overcomes blood volume limitations of other approaches, which might help to implement CTC-based "liquid biopsies" into clinical decision making. Clin Cancer Res; 22(9); 2197-206. (c)2015 AACR. PMID- 26667489 TI - Expression and Function of Phosphodiesterase Type 5 in Human Breast Cancer Cell Lines and Tissues: Implications for Targeted Therapy. AB - PURPOSE: By catalyzing cGMP hydrolysis, phosphodiesterase (PDE) 5 is a critical regulator of its concentration and effects in different (patho)physiologic processes, including cancers. As PDE5 is a known druggable target, we investigated the clinical significance of its expression in breast cancer and the underlying mechanisms by which it may contribute to tumor progression. EXPERIMENTAL DESIGN: PDE5 expression was evaluated in seven breast cancer cell lines by RT-PCR and immunoblotting. To examine the impact of PDE5 on cancer phenotype, MCF-7 cells expressing lower levels of the enzyme were engineered to stably overexpress PDE5. Proliferation was evaluated by MTT assays, motility and invasion by wound-healing/transmigration/invasion assays, transcriptome-profiling by RNA-sequencing, and Rho GTPase signaling activation by GST-pulldown assays and immunoblotting. Clinical relevance was investigated by IHC on tissues and retrospective studies from METABRIC cohort. RESULTS: PDE5 is differentially expressed in each molecular subtype of both breast cancer cell lines and tissues, with higher levels representing a startling feature of HER2-positive and triple negative breast cancers. A positive correlation was established between elevated PDE5 levels and cancers of high histologic grade. Higher PDE5 expression correlated with shorter patient survival in retrospective analyses. On molecular level, stable PDE5 overexpression in Luminal-A-like MCF-7 cells resulted in enhanced motility and invasion through Rho GTPase signaling activation. Treatment of PDE5-stable clones with selective ROCK or PDE5 inhibitors completely restored the less motile and weak invasive behavior of control vector cells. CONCLUSIONS: PDE5 expression enhances breast cancer cell invasive potential, highlighting this enzyme as a novel prognostic candidate and an attractive target for future therapy in breast cancers. Clin Cancer Res; 22(9); 2271-82. (c)2015 AACR. PMID- 26667487 TI - Nicotine Reduces Survival via Augmentation of Paracrine HGF-MET Signaling in the Pancreatic Cancer Microenvironment. AB - PURPOSE: The relationship between smoking and pancreatic cancer biology, particularly in the context of the heterogeneous microenvironment, remains incompletely defined. We hypothesized that nicotine exposure would lead to the augmentation of paracrine growth factor signaling between tumor-associated stroma (TAS) and pancreatic cancer cells, ultimately resulting in accelerated tumor growth and metastasis. EXPERIMENTAL DESIGN: The effect of tobacco use on overall survival was analyzed using a prospectively maintained database of surgically resected patients with pancreatic cancer. Nicotine exposure was evaluated in vitro using primary patient-derived TAS and pancreatic cancer cells independently and in coculture. Nicotine administration was then assessed in vivo using a patient-derived pancreatic cancer xenograft model. RESULTS: Continued smoking was associated with reduced overall survival after surgical resection. In culture, nicotine-stimulated hepatocyte growth factor (HGF) secretion in primary patient derived TAS and nicotine stimulation was required for persistent pancreatic cancer cell c-Met activation in a coculture model. c-Met activation in this manner led to the induction of inhibitor of differentiation-1 (Id1) in pancreatic cancer cells, previously established as a mediator of growth, invasion and chemoresistance. HGF-induced Id1 expression was abrogated by both epigenetic and pharmacologic c-Met inhibition. In patient-derived pancreatic cancer xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression by qRT-PCR and phospho Met levels by ELISA. Similarly, elevated levels of phospho-Met in surgically resected pancreatic cancer specimens correlated with reduced overall survival. CONCLUSIONS: Taken together, these data demonstrate a novel, microenvironment dependent paracrine signaling mechanism by which nicotine exposure promotes the growth and metastasis of pancreatic cancer. PMID- 26667490 TI - Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer. AB - PURPOSE: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. EXPERIMENTAL DESIGN: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. RESULTS: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (kappa = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (kappa = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (kappa = 0.73). CONCLUSIONS: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis. Clin Cancer Res; 22(9); 2177-82. (c)2015 AACR. PMID- 26667492 TI - Impact of pay for performance on behavior of primary care physicians and patient outcomes. AB - BACKGROUND AND OBJECTIVES: Pay-for-performance is a financial incentive which links physicians' income to the quality of their services. Although pay-for performance is suggested to be an effective payment method in many pilot countries (ie the UK) and enjoys a wide application in primary health care, researches on it are yet to reach an agreement. Thus, a systematic review was conducted on the evidence of impact of pay-for-performance on behavior of primary care physicians and patient outcomes aiming to provide a comprehensive and objective evaluation of pay-for-performance for decision-makers. METHODS: Studies were identified by searching PubMed, EMbase, and The Cochrane Library. Electronic search was conducted in the fourth week of January 2013. As the included studies had significant clinical heterogeneity, a descriptive analysis was conducted. Quality Index was adopted for quality assessment of evidences. RESULTS: Database searches yielded 651 candidate articles, of which 44 studies fulfilled the inclusion criteria. An overall positive effect was found on the management of disease, which varied in accordance with the baseline medical quality and the practice size. Meanwhile, it could bring about new problems regarding the inequity, patients' dissatisfaction and increasing medical cost. CONCLUSIONS: Decision-makers should consider the baseline conditions of medical quality and the practice size before new medical policies are enacted. Furthermore, most studies are retrospective and observational with high level of heterogeneity though, the descriptive analysis is still of significance. PMID- 26667491 TI - Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation. AB - PURPOSE: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS. EXPERIMENTAL DESIGN: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. RESULTS: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. CONCLUSIONS: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734-43. (c)2015 AACRSee related commentary by Liu, p. 2602. PMID- 26667493 TI - Fabrication of a biofuel cell improved by the pi-conjugated electron pathway effect induced from a new enzyme catalyst employing terephthalaldehyde. AB - A model explaining the pi-conjugated electron pathway effect induced by a novel cross-linker adopted enzyme catalyst is suggested and the performance and stability of an enzymatic biofuel cell (EBC) adopting the new catalyst are evaluated. For this purpose, new terephthalaldehyde (TPA) and conventional glutaraldehyde (GA) cross-linkers are adopted on a glucose oxidase (GOx), polyethyleneimine (PEI) and carbon nanotube (CNT)(GOx/PEI/CNT) structure. GOx/PEI/CNT cross-linked by TPA (TPA/[GOx/PEI/CNT]) results in a superior EBC performance and stability to other catalysts. It is attributed to the pi bonds conjugated between the aldehyde of TPA and amine of the GOx/PEI molecules. By pi conjugation, electrons bonded with carbon and nitrogen are delocalized, promoting the electron transfer and catalytic activity with an excellent EBC performance. The maximum power density (MPD) of an EBC adopting TPA/[GOx/PEI/CNT] (0.66 mW cm( 2)) is far better than that of the other EBCs (the MPD of EBC adopting GOx/PEI/CNT is 0.40 mW cm(-2)). Regarding stability, the covalent bonding formed between TPA and GOx/PEI plays a critical role in preventing the denaturation of GOx molecules, leading to an excellent stability. By repeated measurements of the catalytic activity, TPA/[GOx/PEI/CNT] maintains its activity to 92% of its initial value even after five weeks. PMID- 26667494 TI - Age-associated differences in response to sevoflurane postconditioning in rats. AB - BACKGROUND: Experimental evidence suggests that anesthetic preconditioning and postconditioning could effectively attenuate myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed at investigating whether there are age associated differences in response to sevoflurane postconditioning during myocardial I/R injury in young and old rats, and explore the underlying molecular mechanisms. METHODS: Young and old rats were subjected to 30 min myocardial ischemia, followed by 2 h of reperfusion, with or without sevoflurane postconditioning. RESULTS: Both 1 and 2 minimal aveolar concentration (MAC) sevoflurane postconditioning reduced infarct size (IS) (34 +/- 3% and 32 +/- 2% vs. 58 +/- 5%, p < 0.05) and apoptotic index (8 +/- 1% and 7 +/- 1% vs. 15 +/- 2%, p < 0.05) in young rats, compared to young control group. In contrast, they could not reduce IS (45 +/- 3% and 43 +/- 3% vs. 47 +/- 3%, p > 0.05) and apoptotic index (28 +/- 3% and 25 +/- 2%, vs. 26 +/- 2%, p > 0.05) in old rats, compared to old control group. Mechanistically, we found that the phosphorylation of both Akt and ERK1/2 but not STAT3 was substantially enhanced after sevoflurane postconditioning in young rats, compared to young control group, but not in old rats, relative to old control group. CONCLUSION: There are age-related differences after exposure to sevoflurane postconditioning that protects young, but not old rat hearts against I/R injury, which may be at least associated with the inability to activate Akt and ERK1/2. PMID- 26667496 TI - Role of mitogen-activated protein kinase pathways in migration of gingival epithelial cells in response to stimulation by cigarette smoke condensate and infection by Porphyromonas gingivalis. AB - BACKGROUND AND OBJECTIVE: Previous studies have shown that cigarette smoke (CS) and periodontal pathogens could alter wound healing responses of gingival epithelial cells. To elucidate molecular mechanisms leading to these epithelial changes, we studied the signaling pathway involved in the modulation of cell migration by CS condensate (CSC) and the infection by a prominent periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC or vehicle control for 24 h. Activation of mitogen-activated protein kinases (MAPK) in cells with or without infection by P. gingivalis was assessed by polymerase chain reaction array and immunoblotting using phospho-specific antibodies. Cell migration was assessed using in vitro wound closure model, and specific pharmacologic inhibitors of MAPK pathways were used to characterize further the extent of involvement of the MAPK pathways. RESULTS: Polymerase chain reaction array showed that gene expression of several members of the MAPK, particularly p38 and JNK, was upregulated more than twofold in Ca9-22 cells stimulated with 10 MUg/mL CSC. Coincubation with P. gingivalis induced a different pattern of gene expression for MAPK pathways, but it did not suppress the MAPK-related genes upregulated by CSC. A significant phosphorylation of ERK1/2 and p38 was observed in cells stimulated with 10 MUg/mL CSC (p < 0.05), whereas coincubation with a higher concentration of CSC (250 MUg/mL) evoked no such activation. P. gingivalis infection resulted in a tendency to reduce the phosphorylation of ERK1/2 and p38, which had been enhanced by stimulation with 10 MUg/mL CSC. Incubation with ERK1/2 and p38 inhibitors significantly reduced the wound closure of CSC-stimulated cells, by approximately 43% and 46%, respectively (p < 0.05). CONCLUSION: CSC exerts effects on the migration of human gingival epithelial cells through the activation of the MAPK ERK1/2 and p38 signaling pathways. P. gingivalis infection attenuates the CSC induced migration at least partly by suppressing the phosphorylation of ERK1/2 and p38, but other pathways are likely to be involved in this modulatory process. PMID- 26667498 TI - Secondary growth of the Arabidopsis hypocotyl-vascular development in dimensions. AB - The secondary thickening of plant organs in extant dicotyledons is a massive growth process that constitutes the major carbon sink in perennial, woody plants. Yet, our understanding of its molecular genetic control has been mostly obtained by its analysis in an herbaceous annual model, Arabidopsis. Recent years have seen increased interest in this somewhat under-researched topic, and various (non )cell autonomous factors that guide the extent and vascular patterning of secondary growth have been identified. Concomitantly, a more detailed understanding of vascular differentiation processes has been obtained through analyses of primary growth, mostly in the root meristem. A future challenge will be the integration of these patterning and differentiation modules together with cambial activity into the 4-dimensional frame of secondary thickening. PMID- 26667495 TI - A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions. AB - The molecular origins of fibrosis affecting multiple tissue beds remain incompletely defined. Previously, we delineated the critical role of the control of extracellular matrix (ECM) stiffening by the mechanosensitive microRNA-130/301 family, as activated by the YAP/TAZ co-transcription factors, in promoting pulmonary hypertension (PH). We hypothesized that similar mechanisms may dictate fibrosis in other tissue beds beyond the pulmonary vasculature. Employing an in silico combination of microRNA target prediction, transcriptomic analysis of 137 human diseases and physiologic states, and advanced gene network modeling, we predicted the microRNA-130/301 family as a master regulator of fibrotic pathways across a cohort of seemingly disparate diseases and conditions. In two such diseases (pulmonary fibrosis and liver fibrosis), inhibition of microRNA-130/301 prevented the induction of ECM modification, YAP/TAZ, and downstream tissue fibrosis. Thus, mechanical forces act through a central feedback circuit between microRNA-130/301 and YAP/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states. Such re conceptualization of interconnections based on shared systems of disease and non disease gene networks may have broad implications for future convergent diagnostic and therapeutic strategies. PMID- 26667499 TI - Identification of signature volatiles to discriminate Candida albicans, glabrata, krusei and tropicalis using gas chromatography and mass spectrometry. AB - Oral candidiasis is the most frequent fungal infection of the oral cavity. Clinical diagnoses require mycological confirmation, which is time-consuming in case of culture testing. The aim of the study was to identify signature volatiles to develop a chairside breath test to diagnose oral candidiasis. Headspaces above Candida albicans, glabrata, tropicalis, krusei cultures, and growth media as control were analysed after eight and 24 h using offline gas chromatography and mass spectrometry. The identification of signature volatiles was assisted using various microbial databases. Retrieved volatile patterns enabled Candida species discrimination in vitro. For C. albicans 3-methyl-2-butanone and styrene and for C. krusei a combination of p-xylene, 2-octanone, 2-heptanone and n-butyl acetate were found to be specific. 1-hexanol was found in C. tropicalis, but is emitted by a variety of other microorganisms. C. glabrata was characterised through the absence of these volatiles. The development of a breath test is a promising approach in confirming suspicions of oral candidiasis. To confirm the retrieved results in vivo, breath tests in affected and healthy subjects have to be performed. PMID- 26667497 TI - The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles. AB - BACKGROUND: Viral infections such as influenza have been shown to predispose hosts to increased colonization of the respiratory tract by pathogenic bacteria and secondary bacterial pneumonia. To examine how viral infections and host antiviral immune responses alter the upper respiratory microbiota, we analyzed nasal bacterial composition by 16S ribosomal RNA (rRNA) gene sequencing in healthy adults at baseline and at 1 to 2 weeks and 4 to 6 weeks following instillation of live attenuated influenza vaccine or intranasal sterile saline. A subset of these samples was submitted for microarray host gene expression profiling. RESULTS: We found that live attenuated influenza vaccination led to significant changes in microbial community structure, diversity, and core taxonomic membership as well as increases in the relative abundances of Staphylococcus and Bacteroides genera (both p < 0.05). Hypergeometric testing for the enrichment of gene ontology terms in the vaccinated group reflected a robust up-regulation of type I and type II interferon-stimulated genes in the vaccinated group relative to controls. Translational murine studies showed that poly I:C administration did in fact permit greater nasal Staphylococcus aureus persistence, a response absent in interferon alpha/beta receptor deficient mice. CONCLUSIONS: Collectively, our findings demonstrate that although the human nasal bacterial community is heterogeneous and typically individually robust, activation of a type I interferon (IFN)-mediated antiviral response may foster the disproportionate emergence of potentially pathogenic species such as S. aureus. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov on 11/3/15, NCT02597647 . PMID- 26667500 TI - Plantar Pressure and Gait Symmetry in Individuals with Fractures versus Tendon Injuries to the Hindfoot. AB - BACKGROUND: The intent of this study was to determine whether differences in function, walking characteristics, and plantar pressures exist in individuals after operative fixation of an intra-articular calcaneal fracture (HFX) compared with individuals with operative repair of an Achilles tendon rupture (ATR). METHODS: Twenty patients (ten with HFXs and ten with ATRs) were recruited approximately 3.5 months after operative intervention. All of the participants completed the Lower Extremity Functional Scale and had their foot posture assessed using the Foot Posture Index. Walking velocity was assessed using a pressure mat system, and plantar pressures were measured using an in-shoe sensor. In addition to between-group comparisons, the involved foot was compared with the uninvolved foot for each participant. RESULTS: There were no differences in age, height, weight, or number of days since surgery between the two groups. The HFX group had lower Lower Extremity Functional Scale scores, slower walking velocities, and different forefoot loading patterns compared with the ATR group. The involved limb of both groups was less pronated. CONCLUSIONS: The results indicate that individuals with an HFX spend more time on their involved limb and walk slower than those with an ATR. Plantar pressures in the HFX group were higher in the lateral forefoot and lower in the medial forefoot and in the ATR group were symmetrically lower in the forefoot. PMID- 26667501 TI - Radiographic Investigation of the Absolute and Relative First Metatarsal Lengths in the Asymptomatic Foot. AB - BACKGROUND: We investigated distortion of measured lengths of the first and second metatarsals between two radiographic views and ultrasound-guided measurements. METHODS: In a case series performed between June 29, 2012, and February 6, 2013, two standard anteroposterior and lateral radiographs of each foot were obtained from 27 asymptomatic participants. Three raters performed blinded radiographic measurements of the first and second metatarsal lengths on each view and compared results. Actual first and second metatarsal lengths were measured using diagnostic ultrasound and were compared with the radiographic measurements. The relative distances between the first and second metatarsals were obtained on the anteroposterior and lateral views and were compared. RESULTS: Absolute first metatarsal length measurements were significantly affected by view (mean difference, 5.3 mm; 95% confidence interval [CI], 4.88 5.78 mm; P < .001), with no significant difference between raters (P = .039). Absolute second metatarsal length measurements were significantly affected by view (mean difference, 2.84 mm; 95% CI, 2.8-3.6 mm) and by rater (P = .024). First and second metatarsal anteroposterior values were 13.9% and 15.3% longer, respectively, than the actual length as measured by ultrasound (P < .001). Relative first metatarsal length was significantly shorter on lateral views (mean difference, 3.85 mm; 95% CI, 2.7-5 mm; P < .001). First metatarsal length was best approximated by the lateral view. CONCLUSIONS: This study demonstrates the effect of radiographic distortion on the measurement of metatarsal length. The lateral view is more accurate than the anteroposterior view for measuring the first metatarsal. Owing to variance of relative metatarsal length on the two views, conclusions regarding a relatively short or long first metatarsal compared with the second metatarsal cannot be drawn. PMID- 26667502 TI - Effect of Obesity Level on the Longitudinal Arch in 7- to 12-Year-Old Rural and Urban Children. AB - BACKGROUND: We sought to evaluate the influence of obesity level on the medial longitudinal arch (MLA) of the foot in 7- to 12-year-old children. METHODS: The study group consisted of 925 children (450 girls and 475 boys). All of the children were subjected to podoscopic foot examination and measurement of weight, height, three skinfolds, fat weight, and fat-free body weight. RESULTS: The most common type of MLA was high-arched foot, which was observed in the left foot of 523 children (56.5%) and in the right foot in 592 children (64%). In almost all of the age groups, high-arched foot was the most common disorder. High-arched foot was more common in girls than in boys, and boys displayed a higher percentage of flatfoot. Also, sex-related differences were more prominent in urban children. There was a strongly positive correlation between obesity level and MLA in the examined group. CONCLUSIONS: These results suggest that the type of foot arch is influenced by parameters such as age, sex, and obesity level. High-arched foot seemed to be the most frequent pathologic abnormality in the examined group, and flatfoot, which was predominant in boys and obese children, diminished with age. High-arched foot was a more common MLA type than flatfoot regardless of obesity level assessed on the basis of body mass index and sum of three skinfolds. PMID- 26667503 TI - Reduction of Dorsal Displacement of the Proximal and Middle Phalanges Using a Neutral or Angled Implant for Joint Arthrodesis to Treat Hammertoe Deformity A Finite Element Study. AB - BACKGROUND: We used finite element analysis to study the mechanical displacements at three planes of the second through fourth hammertoes during the push-off phase of gait using a new neutral or 10 degrees angled memory alloy intramedullary implant (FDA K070598) used for proximal interphalangeal joint arthrodesis. METHODS: After geometric reconstruction of the foot skeleton from computed tomographic images of a 36-year-old man, an intramedullary implant was positioned in the virtual model at the neutral and 10 degrees angled positions at the proximal interphalangeal joints of the second through fourth hammertoes during the push-off phase of gait. The obtained displacement results in three planes were compared with those derived from the nonsurgical foot model using finite element analysis. RESULTS: These results support the successful use of either a neutral or angled implant for proximal interphalangeal joint arthrodesis, with the neutral implant yielding slightly better results. CONCLUSIONS: The neutral implant reduced vertical displacement to a greater extent than did the angled implant. We also highlight the potential risk of iatrogenic curly toe when performing a proximal interphalangeal joint arthrodesis using an angled implant specifically at the fourth toe. PMID- 26667504 TI - A Retrospective Review of Diagnostic Testing for Onychomycosis of the Foot. AB - BACKGROUND: Onychomycosis is a fungal infection of the nail that can be caused by dermatophytes, yeasts, or nondermatophyte molds. To diagnose onychomycosis, a clinician must use the patient's history, physical findings, and diagnostic testing, which can include calcofluor white/potassium hydroxide (KOH) mount, fungal culture (FC), and periodic acid-Schiff (PAS) stain. Some insurance companies require authorization for antifungal medication and request laboratory results to confirm infection. We sought to compare the reliability of KOH, PAS, and FC diagnostic results for confirmation of fungal disease, to determine the sensitivity and specificity of each test, and to investigate the cost of each test. In addition, we statistically observed the relationship between the test results and demographic variables. METHODS: Toenail clippings were obtained from 108 patients clinically diagnosed as having onychomycosis. Diagnostic tests were then performed on each sample; the results were obtained from medical records. RESULTS: For PAS, KOH, and FC, 60.2%, 43.5%, and 39.8% of results, respectively, were positive. Agreement for each pair of tests was slightly higher for FC and KOH. Sensitivities for KOH and PAS were 0.64 and 0.79, respectively. Specificity was 0.79 for KOH and 0.54 for PAS. Both PAS and KOH had a higher percentage of positive test results for men than for women. CONCLUSIONS: Of the three tests evaluated, PAS gives the most consistent positive results and has the highest sensitivity. Therefore, PAS should be considered as the best test to verify clinically significant onychomycosis. PMID- 26667505 TI - Antibiotic Tissue Penetration in Diabetic Foot Infections A Review of the Microdialysis Literature and Needs for Future Research. AB - Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with diabetic foot infections. PMID- 26667506 TI - Risk Factors and Protective Factors for Lower-Extremity Running Injuries A Systematic Review. AB - A review of the scientific literature was performed 1) to identify studies describing the most common running injuries and their relation to the risk factors that produce them and 2) to search for potential and specific protective factors. Spanish and English biomedical search engines and databases (MEDLINE/PubMed, Database Enfermeria Fisioterapia Podologia [ENFISPO], Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature) were queried (February 1 to November 30, 2013). A critical reading and assessment was then performed by the Critical Appraisal Skills Programme Spanish tool. In total, 276 abstracts that contained the selected key words were found. Of those, 25 identified and analyzed articles were included in the results. Injuries result from inadequate interaction between the runner's biomechanics and external factors. This leads to an excessive accumulation of impact peak forces in certain structures that tends to cause overuse injuries. The main reasons are inadequate muscle stabilization and pronation. These vary depending on the runner's foot strike pattern, foot arch morphology, and sex. Specific measures of modification and control through running footwear are proposed. PMID- 26667507 TI - Nonhealing Venous Ulcers and Chronic Venous Outflow Obstruction A Case Report. AB - The etiology of chronic venous insufficiency is typically neglected or misunderstood when treating lower-extremity edema and venous ulcerations. Despite the high prevalence of venous compression syndromes, it is rarely considered when treating venous ulcers and unresolved venous disease. We report a case of bilateral iliac vein outflow obstruction that prohibited venous ulcer healing until properly treated. This case highlights the importance of properly identifying and treating venous compression syndromes to enhance ulcer healing and decrease the risk of venous ulcer recurrence. PMID- 26667508 TI - A Rare Presentation of Transformed, CD30(+) High-Grade Cutaneous T-Cell Lymphoma of the Hallux A Case Report. AB - Cutaneous T-cell lymphoma is a type of non-Hodgkin's lymphoma, which is a neoplasm affecting the lymphatic system. Mycosis fungoides is the most common subset of cutaneous T-cell lymphoma and is often treated conservatively. This neoplasm is most common in adults older than 60 years and does not regularly manifest in the toes. A case is reported of a 70-year-old man seen for a nonhealing hallux ulceration leading to amputation. Histopathologic examination revealed a rare transformed CD30(+) high-grade cutaneous T-cell lymphoma. The morbidity of lymphomas is highly dependent on type and grade. Pharmaceutical precision therapies exist that target specific molecular defects or abnormally expressed genes, such as high expression of CD30. This article focuses on treatment protocol and emphasizes the importance of early diagnosis, determination of cell type, and proper referral of atypical dermatologic lesions. PMID- 26667509 TI - Extrapleural Solitary Fibrous Tumor of the Foot A Case Report. AB - Solitary fibrous tumors are uncommon mesenchymal neoplasms that were initially described as pleural tumors, but in recent years, numerous extrapleural sites have been reported. A solitary fibrous tumor is characterized as a circumscribed, painless mass with a patternless growth pattern, positive CD34 spindle-shaped cells, bcl-2, and dense keloidal collagen with areas of hypercellularity and hypocellularity. This case report describes a 55-year-old male veteran who presented with a rare manifestation of an extrapleural solitary fibrous tumor of the medial right hallux. Microscopic and immunohistochemical findings were consistent with the previously documented characteristics of solitary fibrous tumors. Complete surgical excision of the tumor is the treatment of choice. PMID- 26667512 TI - A Plan for the Future. PMID- 26667510 TI - Acinetobacter baumannii Hallux Infection Secondary to Partial Amputation in a US Soldier A Case Report. PMID- 26667520 TI - Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder. AB - OBJECTIVES: To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder. METHODS: Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non responders for the different active tDCS conditions on both tasks. RESULTS: For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders. CONCLUSIONS: A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder. PMID- 26667521 TI - INCIDENCE DENSITY, PROPORTIONATE MORTALITY, AND RISK FACTORS OF ASPERGILLOSIS IN MAGELLANIC PENGUINS IN A REHABILITATION CENTER FROM BRAZIL. AB - Aspergillosis, an opportunistic mycosis caused by the Aspergillus genus, affects mainly the respiratory system and is considered one of the most significant causes of mortality in captive penguins. This study aimed to examine a 6-yr period of cases of aspergillosis in penguins at the Centro de Recuperacao de Animais Marinhos (CRAM-FURG), Rio Grande, Brazil. A retrospective cohort study was conducted using the institution's records of penguins received from January 2004 to December 2009. Animals were categorized according to the outcome "aspergillosis," and analyzed by age group, sex, oil fouling, origin, prophylactic administration of itraconazole, period in captivity, body mass, hematocrit, and total plasma proteins. A total of 327 Magellanic penguins (Spheniscus magellanicus) was studied, 66 of which died of aspergillosis. Proportionate mortality by aspergillosis was 48.5%, and incidence density was 7.3 lethal aspergillosis cases per 100 penguins/mo. Approximately 75% of the aspergillosis cases occurred in penguins that had been transferred from other rehabilitation centers, and this was considered a significant risk factor for the disease. Significant differences were also observed between the groups in regard to the period of time spent in captivity until death, hematocrit and total plasma proteins upon admission to the center, and body mass gain during the period in captivity. The findings demonstrate the negative impacts of aspergillosis on the rehabilitation of Magellanic penguins, with a high incidence density and substantial mortality. PMID- 26667522 TI - EVALUATION OF THYROID HORMONES AND AS INFLUENCED BY TREATMENT WITH DESLORELIN IN PALLAS' CATS (OTOCOLOBUS (FELIS) MANUL). AB - Thyroid hormones regulate a variety of physiologic functions including metabolism, growth, and reproductive cycling, and these other hormones can impact the thyroid function via the hypothalamic-pituitary axis. For instance, the gonadotropin-releasing hormone agonist, deslorelin, used in nondomestic carnivores for contraception and behavioral control, down-regulates reproductive hormones through this mechanism and so may impact thyroid function. Due to clinical concerns of hypothyroidism in a bachelor group of adult male Pallas' cats (Otocolobus (Felis) manul) which also had deslorelin implants, serum samples from treated captive (n = 8) individuals, untreated captive (n = 25), and free ranging (n = 9) individuals were analyzed for thyroid hormone concentrations. Total and free thyroxine (TT4 and FT4), total and free tri-iodothyronine (TT3 and FT3), and thyroid stimulating hormone (TSH) were measured although, due to sample volume limitations, not every hormone could be analyzed for every sample. Of these hormones, only FT4 was found statistically different between the deslorelin treated and untreated groups. As samples were unevenly distributed across season, true comparison between seasons could not be made. The values reported for the untreated captive and free-ranging group, while representing a small sample size, can serve as a baseline assessment when evaluating the thyroid status of captive Pallas' cats. PMID- 26667523 TI - THE INFLUENCE OF ULTRAVIOLET-B RADIATION ON THE GROWTH OF MARABOU STORK (LEPTOPTILOS CRUMENIFERUS) NESTLINGS IN RELATION TO PLASMA CALCIUM, PHOSPHORUS, AND VITAMIN D3 CONCENTRATIONS. AB - In order to prevent metabolic bone disease in growing captive-bred marabou storks (Leptoptilos crumeniferus), three hatchlings were exposed twice a day for 30 min each time to ultraviolet-B (UVB) radiation. During their first 35 days of life, body weights were monitored weekly, and blood was collected to determine total calcium, phosphorus, 25(OH) cholecalciferol, and 1.25(OH)2cholecalciferol plasma levels. Data were compared with those obtained from two marabou stork nestlings that were raised before, without being exposed to UVB. These two birds developed metabolic bone disease, while the UVB-exposed birds developed into healthy adult animals. Plasma chemistry data obtained in this study demonstrate that nestling marabou storks produce vitamin D3under the influence of UVB radiation. The absence of clinical metabolic bone disease in the nestlings that received UVB compared to the nestlings that were raised with the same diet without UVB radiation and that developed MBD demonstrates the importance of UVB radiation for normal development in this species. PMID- 26667524 TI - SINGLE- VERSUS DOUBLE-DOSE RABIES VACCINATION IN CAPTIVE AFRICAN WILD DOGS (LYCAON PICTUS). AB - The immune responses of 35 captive African wild dogs (Lycaon pictus) to an inactivated rabies virus vaccine were evaluated. Seventeen animals received one 1 ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. Sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. Rabies neutralizing serum antibody titers were measured by rapid fluorescent focus inhibition testing. Within 3 mo postvaccination, all 28 animals that were tested within that time period had seroconverted. Overall, titers were significantly higher among animals given two doses of vaccine than among those given a single dose, although this difference was no longer significant by 15 mo postvaccination. Regardless of initial dose, a single administration of inactivated rabies virus vaccine resulted in long-term elevation of titers in the African wild dogs in this study. In the two individuals followed for greater than 36 mo, both (one from each group) maintained detectable titers. PMID- 26667525 TI - A RARE CASE OF HEPATOCELLULAR CARCINOMA IN THE ARABIAN SAND CAT (FELIS MARGARITA HARRISONI). AB - Primary liver cancer is uncommon and is generally classified as hepatocellular carcinoma (HCC), bile duct carcinoma, neuroendocrine (or carcinoid) tumor, and mesenchymal tumor (sarcoma). Here we describe the gross and histopathology characteristics of a rare HCC in a captive Arabian sand cat (Felis margarita harrisoni) held at Al Ain Zoo, United Arab Emirates. The description of this case in the Arabian sand cat adds to the current knowledge of hepatocellular carcinoma in captive nondomestic felids. PMID- 26667526 TI - HEALTH-SCREENING PROTOCOLS FOR VINACEOUS AMAZONS (AMAZONA VINACEA) IN A REINTRODUCTION PROJECT. AB - Reintroduction is a growing field in the conservation of endangered species. The vinaceous Amazon parrot (Amazona vinacea) is extinct in several areas, and a project to release confiscated individuals to their former range is currently underway. The objective of this study was to evaluate and improve the selection and treatment of individual release candidates by detecting possible pathogen carriers using samples taken before and during release. As part of prerelease health protocols, samples were obtained from 29 parrots on three different occasions while in captivity and once after their release. Samples were screened for paramyxovirus type 1, avian influenza, poxvirus, coronavirus, psittacine herpesvirus 1, Chlamydia psittaci , enteropathogenic Escherichia coli (EPEC), Salmonella spp., and endoparasites. The majority of samples returned negative results, with the exception of two individuals that tested positive for C. psittaci in the first sampling and for Ascaridia spp. in the second pooled sampling. Treatments for C. psittaci and endoparasites were administered prior to release, and negative results were obtained in subsequent exams. The number of positive results for E. coli (non-EPEC) decreased during the rehabilitation period. Adequate quarantine procedures and health examinations greatly minimize disease risks. The protocols employed in this study resulted in acceptable health status in accordance with current environmental legislation in Brazil. Additionally, protocols allowed informed decisions to release candidates, minimized risks, and favored the selection of healthy individuals, thereby contributing to the recovery of this species. It is important to determine appropriate minimum health-screening protocols when advanced diagnostics may not be available or high costs make the tests prohibitive in countries where confiscations occur. We hypothesize that a minimum panel of tests of pooled samples can serve as an alternative approach that minimizes costs and overall workload and supports projects intended to restore and promote flagship species and hamper their illegal trade. PMID- 26667527 TI - SKELETAL MORPHOLOGY OF THE FORELIMB OF MYRMECOPHAGA TRIDACTYLA. AB - Anteater forelimbs are morphologically adapted to obtain food and to provide defense and locomotion. Four species are known, but there are few anatomical studies presenting the morphologic features of each species. The aim of this study was to describe the skeletal morphology of the giant anteater (Myrmecophaga tridactyla) forelimb. Pictures and schematic drawings of six cadavers were created to show the bone morphology. In addition, radiographs and computed tomographs were obtained. The skeletal structure of the forelimb had several notable anatomical features. The scapula had two spines, with apparent differences between infant and adult animals. The humerus had a pectoral ridge, a pectoral tubercle, and a pronounced medial epicondyle that represent the origins of muscles important for fossorial activity. The radius had cranial, lateral, and caudal ridges that became more prominent in older animals, and the distal condyle joint provided enhanced support of the dorsal articulation for the manus. Knowledge of the bone morphology of the forelimb generates a better understanding of giant anteater habits and helps in the diagnosis of skeletal abnormalities and in the routine medical assessment of this species. PMID- 26667528 TI - MULTIDRUG RESISTANCE IN WILD BIRD POPULATIONS: IMPORTANCE OF THE FOOD CHAIN. AB - The presence of multidrug-resistant (MDR) Escherichia coli has recently been reported in wild birds (gulls and birds of prey) that had no apparent exposure to antimicrobials. Little work has been done to assess the role of the food chain in the emergence and spread of MDR E. coli . In this study, we evaluated the presence of MDR E. coli in 29 fecal samples collected from wild birds living in a rehabilitation center (the center receives injured animals found in their natural habitat) and in eight feed samples. In total, 166 E. coli isolates were obtained: 129 from cloacal swabs and 37 from raw feed samples. The antimicrobial resistance profile of these isolates was determined, and we found that 75 isolates showed resistance to five or more drugs, resulting in a total of 38 different antimicrobial resistance patterns. Subsequently, the molecular characterization of 36 isolates, performed by pulsed-field gel electrophoresis, revealed a great similarity between isolates collected from various species of birds and also between these last ones and the ones found in their feed samples. PMID- 26667529 TI - EXPERIMENTAL CHALLENGE STUDY OF FV3-LIKE RANAVIRUS INFECTION IN PREVIOUSLY FV3 LIKE RANAVIRUS INFECTED EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) TO ASSESS INFECTION AND SURVIVAL. AB - The Maryland Zoo in Baltimore experienced an outbreak of Frog virus-3 (FV3)-like ranavirus during the summer of 2011, during which 14 of 27 (52%) of its captive eastern box turtles (Terrapene carolina carolina) survived. To assess survival, immunity, and viral shedding, an experimental challenge study was performed in which the surviving, previously infected turtles were reinfected with the outbreak strain of FV3-like ranavirus. Seven turtles were inoculated with virus intramuscularly and four control turtles received saline intramuscularly. The turtles were monitored for 8 wk with blood and oral swabs collected for quantitative polymerase chain reaction (qPCR). During that time, one of seven (14%) inoculated turtles and none of the controls (0%) died; there was no significant difference in survival. Clinical signs of the inoculated turtles, except for the turtle that died, were mild compared to the original outbreak. Quantitative PCR for FV3-like ranavirus on blood and oral swabs was positive for all inoculated turtles and negative for all controls. The turtle that died had intracytoplasmic inclusion bodies in multiple organs. Three inoculated and two control turtles were euthanized at the end of the study. No inclusion bodies were present in any of the organs. Quantitative PCR detected FV3-like ranavirus in the spleen of a control turtle, which suggested persistence of the virus. The surviving five turtles were qPCR-negative for FV3-like ranavirus from blood and oral swabs after brumation. Quantitative PCR for Terrapene herpesvirus 1 found no association between ranavirus infection and herpesvirus loads. In conclusion, previously infected eastern box turtles can be reinfected with the same strain of FV3-like ranavirus and show mild to no clinical signs but can shed the virus from the oral cavity. PMID- 26667530 TI - HEMATOLOGY AND BIOCHEMISTRY IN CAPTIVE WHITE-NAPED CRANES (GRUS VIPIO). AB - In this retrospective study, 36 hematologic and biochemistry samples from white naped crane (Grus vipio) were analyzed. All birds were housed at a single institution, and samples were obtained between 1990 and 2013. All cranes were healthy at the time of sample collection, and ages ranged from 1 mo to 33 yr old. Cranes below 18 mo old were considered juveniles. Comparisons were made between means for juveniles and adults and for males and females. Significant increases in adults (P < 0.05) were found in the following variables (differences shown in parentheses): packed cell volume (8.3%), mean cell volume (28 fl), monocyte percentage (3.2%), absolute monocyte count (200 * 103/ml), total solids (1.0 g/dl), albumin (0.5 g/dl), and sodium (3 mM/L). Significant decreases in adults (P < 0.05) were found in phosphorus (1.7 mg/dl), creatine phosphokinase (1,146 U/L), alkaline phosphatase (451 U/L), lactate dehydrogenase (149 U/L), and glucose (25 mg/dl). Results from adult male and female cranes were also compared; calcium levels were higher in females (4.68 mg/dl, P < 0.05). Plasma electrophoresis and radioimmunoassay for bile acids were performed on 25 banked serum or plasma samples; results from juvenile and adult samples were also compared. Significant increases in adult birds were found in total protein (1.2 g/dl, P < 0.05) and in all absolute values for all protein types; however, no difference was found when protein fractions were compared. Bile acids were found to decrease in adults (19.9 MUM/L, P < 0.05). PMID- 26667532 TI - PLASMA ELECTROPHORETIC PROFILES IN THE EASTERN MASSASAUGA (SISTRURUS CATENATUS) AND INFLUENCES OF AGE, SEX, YEAR, LOCATION, AND SNAKE FUNGAL DISEASE. AB - The purpose of this study was to establish reference intervals of the protein electrophoretic fractions and the acute-phase proteins hemoglobin binding protein (as determined by the haptoglobin assay) and C-reactive protein (CRP) and assess any possible correlations between varying age class, sex, location (Illinois or Michigan), year, or presence of snake fungal disease (SFD). Banked plasma samples were assayed from 130 eastern massasaugas from 2009 to 2014 in Illinois and Michigan. Snakes from Michigan had higher total protein (mean: 5.50 g/dl), albumin/globulin ratio (0.42), albumin (1.59 g/dl), and gamma globulins (0.55 g/dl) than from snakes in Illinois (4.72 g/dl, 0.29, 1.03 g/dl, 0.38 g/dl, respectively). Snakes in Illinois (22.19 g/ml) had higher CRP than snakes in Michigan (10.89 mg/ml). Adults had higher gamma globulins (0.47 g/dl) than juveniles (0.28 g/dl). Males had higher alpha-2 globulins (0.98 g/dl) and CRP (21.4 mg/ml) than females (0.85, 11.6, respectively). There were no significant differences in absolute plasma proteins in SFD-positive snakes, but the percentage of gamma globulins was significantly higher in positive snakes. Future research in this area can now build on this data to determine changes in population health over time or due to specific environmental or disease threats. PMID- 26667531 TI - ETORPHINE-KETAMINE-MEDETOMIDINE TOTAL INTRAVENOUS ANESTHESIA IN WILD IMPALA (AEPYCEROS MELAMPUS) OF 120-MINUTE DURATION. AB - There is a growing necessity to perform long-term anesthesia in wildlife, especially antelope. The costs and logistics of transporting wildlife to veterinary practices make surgical intervention a high-stakes operation. Thus there is a need for a field-ready total intravenous anesthesia (TIVA) infusion to maintain anesthesia in antelope. This study explored the feasibility of an etorphine-ketamine-medetomidine TIVA for field anesthesia. Ten wild-caught, adult impala ( Aepyceros melampus ) were enrolled in the study. Impala were immobilized with a standardized combination of etorphine (2 mg) and medetomidine (2.2 mg), which equated to a median (interquartile range [IQR]) etorphine and medetomidine dose of 50.1 (46.2-50.3) and 55.1 (50.8-55.4) MUg/kg, respectively. Recumbency was attained in a median (IQR) time of 13.9 (12.0-16.5) min. Respiratory gas tensions, spirometry, and arterial blood gas were analyzed over a 120-min infusion. Once instrumented, the TIVA was infused as follows: etorphine at a variable rate initiated at 40 MUg/kg per hour (adjusted according to intermittent deep-pain testing); ketamine and medetomidine at a fixed rate of 1.5 mg/kg per hour and 5 MUg/kg per hour, respectively. The etorphine had an erratic titration to clinical effect in four impala. Arterial blood pressure and respiratory and heart rates were all within normal physiological ranges. However, arterial blood gas analysis revealed severe hypoxemia, hypercapnia, and acidosis. Oxygenation and ventilation indices were calculated and highlighted possible co-etiologies to the suspected etorphine-induced respiratory depression as the cause of the blood gas derangements. Impala recovered in the boma post atipamezole (13 mg) and naltrexone (42 mg) antagonism of medetomidine and etorphine, respectively. The etorphine-ketamine-medetomidine TIVA protocol for impala may be sufficient for field procedures of up to 120-min duration. However, hypoxemia and hypercapnia are of paramount concern and thus oxygen supplementation should be considered mandatory. Other TIVA combinations may be superior and warrant further investigation. PMID- 26667533 TI - SEROPREVALENCE OF NINE LEPTOSPIRA INTERROGANS SEROVARS IN WILD CARNIVORES, UNGULATES, AND PRIMATES FROM A ZOO POPULATION IN A METROPOLITAN REGION OF CHILE. AB - Serum samples from 130 individuals representing 42 species of carnivores, ungulates, and primates from a population of captive mammals in Metropolitan Region in Chile were tested for antibodies against nine serovars of Leptospira interrogans using the microscopic agglutination test. Ten percent of the animals were seropositive to one or more serovars. Seroprevalence was significantly higher in ungulates (20.4%) compared to carnivores (3.8%) and primates (3.4%). There were no significant differences in seroprevalence among sex and age ranges. The most frequent serovar detected was Autumnalis, present in 53.4% of antibody positive animals. Most positive animals had titers of <=1 : 200, except for a maned wolf ( Chrysocyon brachyurus ) with titers of 1 : 400 against serovar Hardjo. To the authors' knowledge, this is the first report of Leptospira exposure detected in native endangered pudu ( Pudu puda ) and the first confirmation of exposure to L. interrogans in captive wild mammals in Chile. Leptospirosis should be considered as a differential diagnosis in future disease presentation for hepatitis or abortions in captive mammals in Chile. PMID- 26667534 TI - RETROSPECTIVE ANALYSIS OF MORTALITY IN THE NORTH AMERICAN CAPTIVE RED PANDA (AILURUS FULGENS) POPULATION, 1992-2012. AB - Red pandas ( Ailurus fulgens ) are managed as captive populations in both North America and Europe. Regular review of pathology reports is a useful tool for developing veterinary care and husbandry strategies for such populations. Though thorough pathology reviews have been conducted for the European studbook, the North American population has not been reviewed similarly until now. Complete gross and histopathology reports were requested from institutions holding red pandas that died during 1992 through 2012 (n = 530), and reports were received for 95.8% of the individuals, including full necropsy records for 366 red pandas. These reports were classified by subspecies, gender, and age, then reviewed for primary cause of death and secondary pathological findings. A substantial portion of the deaths (40.2%) were neonates (<30 days of age). In both neonatal and juvenile (age = 31-365 days) animals, pneumonia was the most common cause of death. In adult (age = 366 days-10 yr) and geriatric red pandas (age >10 yr), cardiovascular disease was the most common cause of death. Renal disease and gastrointestinal disease also were common pathologic findings in adult and geriatric animals. These findings suggest that stress associated with captivity and husbandry practices, including those associated with social, environmental, and nutritional conditions, may contribute to immune and cardiovascular pathologies, and other common necropsy findings. PMID- 26667535 TI - COMPARISON OF TWO 4.7-MILLIGRAM TO ONE 9.4-MILLIGRAM DESLORELIN ACETATE IMPLANTS ON EGG PRODUCTION AND PLASMA PROGESTERONE CONCENTRATIONS IN JAPANESE QUAIL (COTURNIX COTURNIX JAPONICA). AB - Reproductive disease in captive avian species is common, and medical management is often chosen over surgical removal of the reproductive tract. In a previous study with Japanese quail, a single 4.7-mg deslorelin acetate implant reversibly decreased egg production in 6 out 10 birds for 70 days. The objective of the current study was to evaluate the effects of two 4.7-mg deslorelin acetate implants versus one 9.4-mg implant on egg production and plasma progesterone concentrations in Japanese quail ( Coturnix coturnix japonica). Following a 10 day period of consistent egg laying, 30 adult female Japanese quail were anesthetized and received two 4.7-mg deslorelin implants (n = 10), one 9.4-mg deslorelin implant (n = 10), or a single, identical placebo implant (n = 10) s.c. between the scapulae. Egg production was monitored daily, and plasma progesterone concentrations were measured on days 0, 14, 29, 120, 148, and 182 via enzyme linked immunoassay. All birds were weighed periodically and euthanized at day 182, after which their reproductive tracts were evaluated at gross necropsy. Seven out of 10 birds treated with two 4.7-mg implants ceased egg laying 1 wk after implantation and remained nonovulatory for approximately 100 days. Cessation of egg laying for the 9.4-mg treatment group occurred in 7 out of 10 birds; onset was variable (weeks 5-12) and continued for the remainder of the study period. Plasma progesterone concentrations for deslorelin treatment groups were not significantly different compared to the placebo group at any time point. In conclusion, the two 4.7-mg and the one 9.4-mg implant treatments ceased egg laying in a similar number of birds, but the 9.4-mg implant had a slower onset of action and the effects on egg laying were inconsistent throughout the study period. Further studies evaluating use of deslorelin acetate in other avian species are needed. PMID- 26667536 TI - A RETROSPECTIVE STUDY OF PATHOLOGIC FINDINGS IN CAPTIVE ROCK HYRAX (PROCAVIA CAPENSIS) IN THE UNITED STATES. AB - A retrospective examination of gross and histologic reports was performed to find common lesions in young and adult captive rock hyrax ( Procavia capensis ) from multiple zoo populations. One hundred and thirty-seven reports were analyzed from specimens that were submitted to Northwest ZooPath from 1997 to 2013. Histologic findings from necropsy and biopsy reports and causes of mortality only from necropsy reports were compiled to determine the most common findings. Within the study population, 41 (30%) were male, 62 (45%) were female, and the remainder (34, 25%) were of undetermined sex. Of the 111 necropsies, 87 (78%) died naturally, and 24 (22%) were euthanatized. There were 26 (19%) biopsies with no known status of the animal. The most frequent causes of death or reason for euthanasia were bacterial septicemia (n = 29, 21%) and degenerative cardiomyopathy (n = 29, 21%). The other most prevalent lesions were hemosiderosis (n = 55, 40%), pancreatic islet and interstitial fibrosis (n = 36, 26%), pneumonia of undetermined cause (n = 26, 19%), enteritis/colitis (n = 24, 18%), and renal tubular necrosis (n = 20, 15%). In many animals of this study population (n = 115, 84%), multiple lesions affecting multiple organs were found. PMID- 26667537 TI - DIAGNOSING LYMPHOPROLIFERATIVE DISEASE VIRUS IN LIVE WILD TURKEYS (MELEAGRIS GALLOPAVO) USING WHOLE BLOOD. AB - Lymphoproliferative disease virus (LPDV) is a retrovirus that infects wild and domestic turkeys ( Meleagris gallopavo ). The first cases of LPDV in the United States were diagnosed in 2009, and subsequent surveillance has revealed the virus to be widespread in wild turkey populations throughout the eastern half of the country. More research is needed to determine whether LPDV is having a negative effect on turkey populations, but progress has been impeded by the lack of a simple method for diagnosing the virus in living birds. Infected animals may appear asymptomatic, and diagnostics currently rely on tissue or bone marrow, which can be difficult to obtain. This study investigated the reliability of polymerase chain reaction (PCR) to detect LPDV in whole blood, compared with previous methods using buffy coat (concentrated white blood cells) and bone marrow. Paired samples of whole blood and buffy coat were collected from 137 live turkeys and paired samples of whole blood and bone marrow were collected from 32 turkeys postmortem. Compared with buffy coat, whole blood had 97% sensitivity and 100% specificity. When compared with bone marrow, whole blood had 100% sensitivity and 89% specificity. Both comparisons had a high degree of agreement using Cohen's kappa statistic. Based on these results, PCR of whole blood provides detection of LPDV in living birds that is on par with both buffy coat and bone marrow. PMID- 26667538 TI - COMPARISON OF CHEMICAL AND SURGICAL VASECTOMY ON TESTICULAR ACTIVITY IN FREE ROAMING HORSES (EQUUS CABALLUS). AB - Free-roaming horse (Equus caballus) management is a complex issue incorporating social, economic, emotional, political, and environmental factors. Currently, few proven field techniques exist for managing free-roaming horse population growth, which can reach 20-25% annually. Although there are several strategies available for sterilizing mares when managing free-roaming horse populations, surgical vasectomy is the only method used in the field for stallions. Some managers believe that surgically vasectomizing dominant stallions would have significant effects on reducing horse populations. However, sterilizing only dominant harem stallions results in a relatively modest reduction in population growth as substantial reproduction may occur even when 100% of the dominant harem stallions are sterilized if other males perform as little as 10% of the breeding. The overall goal of the current project was to evaluate the efficacy of a novel nonsurgical method for sterilizing free-roaming horses (chemical vasectomy). In September of 2013, stallions that had been previously surgically vasectomized (SURG, n = 25), previously chemically vasectomized (CHEM, n = 16), or untreated (CONT, n = 32) were captured and surgically castrated in preparation for adoption. When comparing both sterilization methods to CONT, serum testosterone and estrone sulfate concentrations did not differ (P > 0.05), suggesting that these methods for sterilizing free-roaming stallions would not disrupt herd social hierarchy. However, similar to the CONT, all CHEM stallions had sperm present within the vas deferens seminal fluid samples. CHEM stallions had more morphologically abnormal sperm than did CONT stallions but it is not known if this affected the actual fertility. Additional research is needed using alternative sclerosing agents for chemical vasectomy in free-roaming horse populations. PMID- 26667539 TI - PULMONARY ARTERIAL DISEASE ASSOCIATED WITH RIGHT-SIDED CARDIAC HYPERTROPHY AND CONGESTIVE HEART FAILURE IN ZOO MAMMALS HOUSED AT 2,100 M ABOVE SEA LEVEL. AB - Subacute and chronic mountain sickness of humans and the related brisket disease of cattle are characterized by right-sided congestive heart failure in individuals living at high altitudes as a result of sustained hypoxic pulmonary hypertension. Adaptations to high altitude and disease resistance vary among species, breeds, and individuals. The authors conducted a retrospective survey of right-sided cardiac hypertrophy associated with pulmonary arterial hypertrophy or arteriosclerosis in zoo mammals housed at Africam Safari (Puebla, Mexico), which is located at 2,100 m above sea level. Seventeen animals with detailed pathology records matched the study criterion. Included were 10 maras (Dolichotis patagonum), 2 cotton-top tamarins (Saguinus oedipus oedipus), 2 capybaras (Hydrochaeris hydrochaeris), and 1 case each of Bennet's wallaby (Macropus rufogriseus), nilgai antelope (Boselaphus tragocamelus), and scimitar-horned oryx (Oryx dammah). All had right-sided cardiac hypertrophy and a variety of arterial lesions restricted to the pulmonary circulation and causing arterial thickening with narrowing of the arterial lumen. Arterial lesions most often consisted of medial hypertrophy or hyperplasia of small and medium-sized pulmonary arteries. All maras also had single or multiple elevated plaques in the pulmonary arterial trunk consisting of fibrosis, accompanied by chondroid metaplasia in some cases. Both antelopes were juvenile and died with right-sided congestive heart failure associated with severe pulmonary arterial lesions. To the authors' knowledge, this is the first description of cardiac and pulmonary arterial disease in zoo mammals housed at high altitudes. PMID- 26667540 TI - EVALUATION OF DIAGNOSTIC ACCURACY OF THE COMPARATIVE TUBERCULIN SKIN TEST IN REHABILITANT BORNEAN ORANGUTANS (PONGO PYGMAEUS). AB - The tuberculin skin test (TST) has been the mainstay of tuberculosis (TB) testing in primates for decades, but its interpretation in orangutans (Pongo spp.) is challenging, because many animals react strongly, without evidence of infection with Mycobacterium tuberculosis complex. One explanation is cross-reactivity with environmental nontuberculous mycobacteria (NTM). The use of a comparative TST (CTST), comparing reactivity to avian (representing NTM) and bovine (representing tuberculous mycobacteria) tuberculins aids in distinguishing cross-reactivity due to sensitization by NTM from shared antigens. The specificity of the TST can be increased with the use of CTST. We considered three interpretations of the TST in rehabilitant Bornean orangutans ( Pongo pygmaeus ) using avian purified protein derivative (APPD; 25,000 IU/ml) and two concentrations of bovine purified protein derivative (BPPD; 100,000 and 32,500 IU/ml). The tests were evaluated for their ability to identify accurately seven orangutans previously diagnosed with and treated for TB from a group of presumed negative individuals (n = 288 and n = 161 for the two respective BPPD concentrations). BPPD at 32,500 IU/ml had poor diagnostic capacity, whereas BPPD at 100,000 IU/ml performed better. The BPPD only interpretation had moderate sensitivity (57%) and poor specificity (40%) and accuracy (41%). The comparative interpretation at 72 hr had similar sensitivity (57%) but improved specificity (95%) and accuracy (94%). However, best results were obtained by a comparative interpretation incorporating the 48- and 72-hr scores, which had good sensitivity (86%), specificity (95%) and accuracy (95%). These data reinforce recommendations that a CTST be used in orangutans and support the use of APPD at 25,000 IU/ml and BPPD at 100,000 IU/ml. The highest score at each site from the 48- and 72-hr checks should be considered the result for that tuberculin. If the bovine result is greater than the avian result, the animal should be considered a TB suspect. PMID- 26667541 TI - SEROLOGIC SURVEY AND RESULTS OF URINARY PCR TESTING FOR LEPTOSPIROSIS IN CAPTIVE BLACK-TAILED PRAIRIE DOGS (CYNOMYS LUDOVICIANUS). AB - Leptospirosis is an important zoonotic disease occurring clinically and subclinically in humans and a wide variety of mammal species worldwide. Often, rodents and wild animals are identified as important reservoirs for the disease. Twenty-two captive black-tailed prairie dogs (Cynomys ludovicianus) housed within a zoo were examined as part of a routine census and preventive medicine program. During examinations, blood and urine were collected to screen for exposure to, or infection with, leptospirosis. All animals were apparently healthy at the time of examination. Leptospira microscopic agglutination test identified 12 of 22 (54.5%) prairie dogs with antibody titers >=1 : 100 against Leptospira interrogans serovar bratislava on initial serologic examination. All prairie dogs within this collection were serologically negative for L. interrogans serovars canicola, hardjo, icterohaemorrhagiae, and pomona and Leptospira kirschneri serovar grippotyphosa. Leptospira polymerase chain reaction (PCR) testing of urine was negative in all animals tested. This report describes evidence that captive prairie dogs may be exposed to leptospirosis, most likely from wild rodent reservoirs; however, serum titers are low, and lack of leptospiral DNA detected by PCR indicates that these captive animals are unlikely to be important reservoirs for the disease. PMID- 26667542 TI - VALUES OF TRACE ELEMENTS SELENIUM, COPPER, ZINC, AND IODINE AND OF VITAMIN E IN CAPTIVE LESSER KUDUS (TRAGELAPHUS IMBERBIS). AB - Lesser kudus (Tragelaphus imberbis) have been kept in Zoo Basel since 1956. Juvenile mortality used to be high, and a recent study to reveal pathologic findings identified white muscle disease as a major contributor to this problem. Therefore, a retrospective study was initiated using 16 stored serum samples from lesser kudus from 2000 to 2013 to determine the concentration of selected trace elements, including selenium, copper, zinc, and iodine. Additionally, three serum samples were used to measure serum vitamin E values. Serum analysis revealed that copper, zinc, and iodine values were within reference ranges for domestic ruminants, and the supplementation status of these trace elements was assumed to be adequate. In contrast, vitamin E levels were low and selenium levels were scarce in several animals, indicating a deficiency of these essential micronutrients. The results of the analyses are compared with literature references. PMID- 26667543 TI - RETROSPECTIVE INVESTIGATION OF CATARACT MANAGEMENT IN AVIAN SPECIES IN A ZOOLOGIC COLLECTION. AB - A review of avian cataracts at the Wildlife Conservation Society's Bronx Zoo between 1992 and 2011 was conducted. Ninety cataracts in 54 birds from 42 species were identified. Cataracts were found primarily during examination for ocular abnormalities (29/54, 53.7%) or opportunistically (13/54, 24.1%) and were most commonly diagnosed as mature (22/90, 24.4%). Systemic medical conditions diagnosed in these birds included West Nile virus (4/54, 7.4%), head trauma (3/54, 5.6%), plumbism and Salmonella Pullorum (1/54, 1.9%), Marek's disease (1/54, 1.9%), leukocytosis (1/54, 1.9%), and hyperglycemia (1/54, 1.9%). Cataracts were progressive in seven birds of four species. Unilateral enucleation was performed in 2/54 (3.7%) birds, and 12/54 (22.2%) underwent cataract removal (phacoemulsification in 16 eyes and standard extracapsular cataract extraction in 2 eyes). Concurrent ocular abnormalities, such as corneal scarring and lens induced uveitis, were seen in 2/18 (11.1%) eyes preoperatively in the group undergoing cataract removal, 2/2 (100%) eyes preoperatively in the group undergoing enucleation, and 33/70 (47.1%) of eyes that did not undergo surgery. For birds undergoing cataract removal, complications included successfully treated cardiorespiratory arrest intraoperatively (1/12, 8.3%) as well as postanesthetic complications of acute respiratory distress and tracheal stricture (2/12, 16.7%). The most common postoperative ocular abnormalities included posterior capsular opacity (4/18 eyes, 22.2%) and corneal scarring (2/18 eyes, 11.1%). Lens cortical regrowth and marked posterior lens capsular opacity occurred in one eye of one bird after phacoemulsification, necessitating a second ocular surgery. A successful outcome, as determined by improved postoperative visual acuity, was seen in 10/12 (83.3%) birds undergoing cataract removal, and 5/12 (41.7%) of these birds were alive >3 yr after surgery. The results of this review will aid clinicians in identifying common stages of cataracts, determining eligibility for cataract surgery, and managing postoperative complications in avian patients. PMID- 26667544 TI - COMPARISON OF ETORPHINE-ACEPROMAZINE AND MEDETOMIDINE-KETAMINE ANESTHESIA IN CAPTIVE IMPALA (AEPYCEROS MELAMPUS). AB - Impala (Aepyceros melampus) are a notoriously difficult species to manage in captivity, and anesthesia is associated with a high risk of complications including mortality. The aim of this study was to compare an opioid-based protocol with an alpha-2 agonist-based protocol. Nine female impala were studied in a random cross-over design. Subjects received either an etorphine-acepromazine (EA) protocol: 15 MUg/kg etorphine and 0.15 mg/kg acepromazine, or a medetomidine ketamine (MK) protocol: 109 MUg/kg medetomidine and 4.4 mg/kg ketamine on day 1. Anaesthesia was repeated 3 days later with the alternative protocol. Subjective assessments of the quality of induction, muscle relaxation, and recovery were made by a blinded observer. Objective monitoring included blood pressure, end tidal CO2, regional tissue oxygenation, and blood gas analysis. EA provided a significantly quicker (mean EA, 7.17 mins; MK, 17.6 mins) and more-reliable (score range EA, 3-5; MK, 1-5) induction. Respiratory rates were lower for EA with higher end-tidal CO2, but no apnoea was observed. As expected, blood pressures with EA were lower, with higher heart rates; however, arterial oxygenation and tissue oxygenation were equal or higher than with the MK protocol. In conclusion, at these doses, EA provided superior induction and equivalent muscle relaxation and recovery with apparent improved oxygen tissue delivery when compared to MK. PMID- 26667545 TI - VORICONAZOLE TOXICITY IN MULTIPLE PENGUIN SPECIES. AB - Aspergillosis is a common respiratory fungal disease in penguins managed under human care. Triazole antifungal drugs, including itraconazole, are most commonly used for treatment; however, itraconazole treatment failures from drug resistance are becoming more common, requiring newer treatment options. Voriconazole, a newer triazole, is being used more often. Until recently, no voriconazole pharmacokinetic studies had been performed in penguins, leading to empiric dosing based on other avian studies. This has led to increased anecdotal reporting of apparent voriconazole toxicity in penguins. This report describes 18 probable and 6 suspected cases of voriconazole toxicity in six penguin species from nine institutions: 12 African penguins (Spheniscus demersus), 5 Humboldt penguins (Spheniscus humboldti), 3 Magellanic penguins (Spheniscus magellanicus), 2 gentoo penguins (Pygoscelis papua papua), 1 macaroni penguin (Eudyptes chrysolophus), and 1 emperor penguin (Aptenodytes forsteri). Observed clinical signs of toxicity included anorexia, lethargy, weakness, ataxia, paresis, apparent vision changes, seizure-like activity, and generalized seizures. Similar signs of toxicity have also been reported in humans, in whom voriconazole therapeutic plasma concentration for Aspergillus spp. infections is 2-6 MUg/ml. Plasma voriconazole concentrations were measured in 18 samples from penguins showing clinical signs suggestive of voriconazole toxicity. The concentrations ranged from 8.12 to 64.17 MUg/ml, with penguins having plasma concentrations above 30 MUg/ml exhibiting moderate to severe neurologic signs, including ataxia, paresis, and seizures. These concentrations were well above those known to result in central nervous system toxicity, including encephalopathy, in humans. This case series highlights the importance of species-specific dosing of voriconazole in penguins and plasma therapeutic drug monitoring. Further investigation, including pharmacokinetic studies, is warranted. The authors recommend caution in determining voriconazole dosages for use in penguin species. PMID- 26667546 TI - FOLLICULAR CELL CARCINOMA OF THE THYROID GLAND IN THREE CAPTIVE AGED RACCOON DOGS (NYCTEREUTES PROCYONOIDES). AB - The clinical and histologic features of thyroid carcinoma in raccoon dogs have not been previously reported. Three of four raccoon dogs (Nyctereutes procyonoides) over 8 yr of age at the Nogeyama Zoological Gardens developed thyroid follicular cell carcinomas that were detected at necropsy. The affected raccoon dogs were rescued from the wild and were housed at the Nogeyama Zoological Gardens for 8 yr 8 mo, 8 yr 10 mo, and 10 yr 3 mo, respectively. Although all of them appeared lethargic and developed partial alopecia or desquamation of their skin, they did not display any other specific clinical signs associated with a thyroid lesion. Serum thyroid hormone values were examined in two of the affected raccoon dogs and the average and standard deviation values (free-thyroxin [FT4]: 0.078 +/- 0.077 pM/L and 0.062 +/- 0.0039 pM/L; free-triiodothyronine [FT3]: 3.261 +/- 0.765 pM/L and 3.407 +/- 0.919 pM/L) were lower than the reference range (FT4: 0.141 +/- 0.117 pM/L; FT3: 5.139 +/- 2.412 pM/L) derived from a clinically normal raccoon dog. On necropsy, the thyroid lobes were markedly enlarged bilaterally. Histopathologically, the neoplastic cells in the thyroid gland appeared round or oval and columnar or cuboidal with minimal heteromorphism. Moreover, mostly small (but occasionally large) follicles were identified, and the neoplastic cells had infiltrated into the surrounding capsule and blood vessels. The histopathologic features of the thyroid tumors in the raccoon dogs revealed that the tumors were derived from follicular cells. PMID- 26667548 TI - ANTEMORTEM DIAGNOSIS OF CYSTIC ENDOMETRIAL HYPERPLASIA AND SUCCESSFUL OVARIOHYSTERECTOMY IN AN AFRICAN WARTHOG (PHACOCHOERUS AFRICANUS). AB - During a routine geriatric examination on a 9-yr-old, nulliparous female African warthog (Phacochoerus africanus), a severely enlarged, mixed echogenicity uterus was discovered during transabdominal ultrasound. Ovariohysterectomy (OVH) was elected and performed due to concern for a potential neoplastic condition. Postoperatively, the warthog was treated prophylactically with metoclopramide and ranitidine to promote gastrointestinal motility and prevent postoperative ileus. The gross appearance and histopathology confirmed the presence of extensive widely disseminated cystic changes consistent with cystic endometrial hyperplasia (CEH) and multiple para-ovarian cysts. Uterine pathology, including CEH, is a common condition in domestic potbellied pigs (Sus scrofa), and as a result, it is recommended to perform an OVH at an early age. The advanced uterine changes may have accounted for this animal's history of infertility. This case provides evidence that nulliparity may be associated with the development of uterine pathology in warthogs. Increased knowledge of reproductive pathology will aid in improved management strategies for breeding nondomestic suids. PMID- 26667547 TI - REPRODUCTIVE NEOPLASMS IN WILD AND LONG-TERM CAPTIVE FEMALE FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS). AB - Few reports of neoplastic diseases in manatees exist in the veterinary literature. This case series presents reproductive neoplasia noted in eight wild and long-term captive female Florida manatees (Trichechus manatus latirostris) obtained through carcass recovery and animal rehabilitation programs between April 2009 and May 2014. All cases were evaluated histologically, and diagnoses of uterine carcinoma (n = 1), granulosa cell tumor (n = 2), ovarian adnexal tumor (n = 1), and leiomyoma (n = 5) were made. The underlying cause of tumor development and effects on reproductive success is currently unknown, but possible asymmetric reproductive aging and/or a correlation between obesity and reproductive disorder in long-term nonreproductive female manatees are of interest and warrant further investigation. PMID- 26667549 TI - MANAGEMENT OF A PATENT URACHUS AND YOLK COELOMITIS IN A PREHENSILE-TAILED SKINK (CORUCIA ZEBRATA). AB - An 11-day-old, captive-born, male prehensile-tailed skink (Corucia zebrata) was evaluated for a chronically swollen umbilicus. On presentation, the skink appeared dehydrated and weak. The umbilical stump was sensitive, edematous, and erythematous. Yellow fluid was readily expressed during palpation of the surrounding area, suggestive of urine. Following several days of supportive care, a positive contrast cloacagram supported the diagnosis of a patent urachus. An exploratory celiotomy was performed, confirming yolk coelomitis and a patent urachus. Both were corrected surgically, and the skink improved steadily thereafter. This report confirms the presence of a urinary bladder in C. zebrata and is the first report of a patent urachus in a reptile. Surgical intervention and medical management of concurrent infectious coelomitis were curative in this case. PMID- 26667550 TI - MEDICAL MANAGEMENT OF LEIOMYOMATA AND SUSPECTED ENDOMETRIOSIS IN AN ALLEN'S SWAMP MONKEY (ALLENOPITHECUS NIGROVIRIDUS). AB - A 13-yr-old female nulliparous Allen's swamp monkey (Allenopitchecus nigroviridis) presented with intermittent excessive vaginal bleeding, cyclical lethargy, and a history of irregular menstrual cycles. Abdominal ultrasonography revealed a subjectively thickened, irregular endometrium, multiple leiomyomata (uterine fibroids), and bilateral anechoic foci on the ovaries. Treatment was initiated with leuprolide acetate i.m. monthly for 6 mo. Recheck ultrasound at 3 mo showed a decrease in leiomyoma diameter and no evidence of active follicles on the ovaries. Eleven months following completion of treatment, clinical signs recurred and the animal was treated with a deslorelin implant. Since implant placement, no vaginal bleeding has been noted. PMID- 26667551 TI - RADIATION THERAPY OF A PRESUMPTIVE URETHRAL TRANSITIONAL CELL CARCINOMA IN AN EASTERN GRAY SQUIRREL (SCIURUS CAROLINENSIS). AB - An adult female Eastern gray squirrel (Sciurus carolinensis), with a previous history of primary renal transitional cell carcinoma treated by nephrectomy, was diagnosed with a metastatic urethral transitional cell carcinoma (TCC) utilizing the veterinary bladder tumor antigen test in combination with other noninvasive diagnostic tests. The squirrel was treated with piroxicam and external beam radiation therapy given in 18 treatments over 30 days to achieve a total of 54 gray. Mild to moderate side effects from the pelvic irradiation were self limiting and easily managed. Resolution of clinical signs was achieved for approximately 6 mo until recurrence of metastasis. This report represents the first published account of both TCC and external beam radiation therapy in an Eastern gray squirrel. PMID- 26667552 TI - FOCUSED ASSESSMENT WITH SONOGRAPHY AS AN AID FOR THE DIAGNOSIS OF GASTROINTESTINAL PERFORATION IN A BOBCAT ( FELIS RUFUS ). AB - A 10-yr-old female spayed bobcat (Felis rufus) presented with a 3-day history of lethargy, anorexia, and two episodes of vomiting. An emergency field visit was scheduled to perform abdominal radiography and ultrasonography. The bobcat was assessed to be approximately 5-10% dehydrated, on the basis of decreased skin turgor and tacky mucous membranes. Free peritoneal gas, reduced abdominal serosal detail, and an abnormal-appearing right-sided intestinal segment were identified in the abdominal radiographs. However, the emergency field clinicians were not knowledgeable of these abnormalities, because the radiographs could not be processed in the field. During an initial complete abdominal ultrasound evaluation, a nondependent hyperechoic interface with reverberation artifact suggestive of intestinal or free gas and focal intestinal changes indicative of marked enteritis or peritonitis were identified. Free peritoneal fluid was not present on initial examination. In a focused abdominal sonography for trauma (FAST) scan, made after subcutaneous fluid administration, a small volume of anechoic free fluid was present in the peritoneal space. With ultrasound guidance, the fluid was aspirated and appeared grossly turbid. This fluid was subsequently confirmed as septic suppurative effusion, secondary to a foreign body-associated intestinal perforation. The use of a FAST scan is well described in human medicine, and to a limited degree in veterinary literature. This case represents a novel application of FAST scanning in an emergency field setting in a nontraumatized patient. This case report illustrates the utility of the FAST scan in yielding critical clinical information after fluid resuscitation in a zoological setting. PMID- 26667553 TI - SUCCESSFUL SURGICAL TREATMENT OF OBSTRUCTIVE LIVER DISEASE CAUSED BY A BILIARY CALCULUS IN A CAPTIVE CHIMPANZEE (PAN TROGLODYTES). AB - A 40-yr-old female chimpanzee (Pan troglodytes) presented with intermittent, short-duration episodes of nonspecific clinical signs that included lethargy and reduced responsiveness to external stimuli. Clinical examination and diagnostics suggested obstructive hepatic disease, which was confirmed by subsequent ultrasonographic examination. During routine laparotomy, a biliary calculus was removed from the distal common bile duct and the gallbladder was removed, which resulted in complete clinical recovery. The biliary calculus was analyzed as a mixed composition of predominantly cholesterol, bilirubin, and calcium. PMID- 26667554 TI - ACUTE PHASE PROTEIN AND ELECTROPHORESIS PROTEIN FRACTION VALUES FOR CAPTIVE AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER). AB - Protein electrophoresis has recognized applications in determining the health status of various species. While reference intervals for electrophoresis have been determined for psittacine and raptor species, there are none reported for Phoenicopteriformes species. Reference intervals for haptoglobin and protein fractions obtained by electrophoresis were determined for the American flamingo (Phoenicopterus ruber) based on plasma samples from 39 captive birds. The reference intervals were as follows: haptoglobin, 0.17-0.8 mg/ml; total protein, 3.65-6.38 g/dl; prealbumin, 0.26-1.9 g/dl; albumin, 1.51-3.12 g/dl; alpha-1 globulin, 0.06-0.38 g/dl; alpha-2 globulin, 0.17-0.67 g/dl; beta globulin, 0.38 1.33 g/dl; gamma globulin, 0.26-0.68 g/dl; albumin : globulin ratio, 0.93-2.17. As captive flamingos often suffer from pododermatitis, feet of all flamingos were scored to determine if pododermatitis would be reflected in the acute phase proteins. Spearman rank correlation was performed on each of the protein fractions and pododermatitis scores, and only albumin had a significant correlation. This indicates that albumin, as a negative acute phase protein, may be a marker for this disease process. PMID- 26667555 TI - RENAL AND CLOACAL CRYPTOSPORIDIOSIS (CRYPTOSPORIDIUM AVIAN GENOTYPE V) IN A MAJOR MITCHELL'S COCKATOO (LOPHOCHROA LEADBEATERI). AB - A 7-yr-old male Major Mitchell's cockatoo (Lophochroa leadbeateri) presented with a recent history of lethargy and anorexia. Physical examination revealed poor body condition and cloacal prolapse. Abnormalities on serum chemistry included severe hyperuricemia and hyperphosphatemia with a low calcium-to-phosphorus ratio. Symptomatic treatment was initiated including intravenous fluids and antibiotics. The bird continued to decline and died within a few days. Visceral gout and renal and cloacal pathology were observed on gross necropsy. Histopathology revealed chronic inflammation within the kidney, ureter, and cloaca in association with protozoal organisms and an invasive cloacal adenocarcinoma tumor. The location and morphology was consistent with Cryptosporidium sp., confirmed by immunohistochemistry and molecular testing. Direct sequencing identified Cryptosporidium avian genotype V. To the author's knowledge, this is the first reported infection of Cryptosporidium avian genotype V associated with clinical disease in birds and the first renal Cryptosporidium infection in a psittacine. PMID- 26667556 TI - MANAGEMENT OF OMPHALOPHLEBITIS AND UMBILICAL HERNIA IN THREE NEONATAL GIRAFFE (GIRAFFA CAMELOPARDALIS). AB - Umbilical disorders, including omphalophlebitis, omphaloarteritis, external umbilical abscesses, urachal abscesses, patent urachus, and umbilical hernias, represent a significant challenge to the health and well-being of a neonate. The three neonatal giraffe (Giraffa camelopardalis) in this report were evaluated for umbilical swellings. Two developed omphalophlebitis, and one had an uncomplicated umbilical hernia. Omphalophlebitis is an inflammation and/or infection of the umbilical vein. Giraffe calves with a failure of passive transfer may be predisposed and should be thoroughly evaluated for the condition. Umbilical hernias result from a failure of the umbilical ring to close after parturition or from malformation of the umbilical ring during embryogenesis. These problems were surgically corrected for all three individuals, although one died due to postsurgical complications. The risks involved include anesthetic complications, surgical dehiscence, and maternal rejection. Early detection and surgical intervention are recommended for the correction of omphalophlebitis and umbilical hernias in neonatal giraffe. PMID- 26667557 TI - NUPTIAL PAD AMPUTATION IN AN AMERICAN BULLFROG (LITHOBATES CATESBEIANUS) WITH SQUAMOUS CELL CARCINOMA. AB - A 7-yr-old male captive American bullfrog (Lithobates catesbeianus) presented with a 2-wk history of an enlarged, ulcerated nuptial pad on the mediopalmar surface of the first digit of the left carpus. A 3-mm wedge biopsy of the mass was not diagnostic and differentials included an epidermal inclusion cyst or squamous cell carcinoma. No fungal or acid-fast organisms were cultured or noted on impression smear. Wide surgical resection of the mass and associated first digit were performed. Histopathology confirmed squamous cell carcinoma associated with the dermal nuptial gland with neoplastic cells extending close to deep surgical margins. Two months after surgery, no recurrence was noted. Although experimental tumor studies in amphibians are well documented, clinical reports of cutaneous neoplasia management in captive amphibians are scarce. Squamous cell carcinoma should be considered as a differential diagnosis when male anurans present with nuptial gland enlargement. PMID- 26667558 TI - LAPAROSCOPIC SALPINGECTOMY IN TWO CAPTIVE LEOPARDS (PANTHERA PARDUS) USING A SINGLE PORTAL ACCESS SYSTEM. AB - Laparoscopic salpingectomy was performed in two adult leopards (Panthera pardus) using a single portal access system, with a multicannulated single-incision laparoscopic surgery port, without any complications. The poorly developed ovarian bursa provided easy access to the uterine tube for salpingectomy. Laparoscopic salpingectomy can be safely performed in the leopard using a single portal access system. PMID- 26667559 TI - MANAGEMENT OF TOXIC MASTITIS IN A BABIRUSA (BABYROUSA CELEBENSIS). AB - A 1 yr 8 mo-old, previously healthy, primiparous female babirusa (Babyrousa celebensis) presented acutely recumbent and minimally responsive approximately 36 hr after giving birth to a single piglet. Toxic mastitis was diagnosed based on physical examination and laboratory results. The mammary tissue was firm, discolored, and produced negligible amounts of milk. All of the teats were eventually affected, resulting in the inability to provide adequate nutrition to the piglet. Although toxic mastitis has a poor prognosis in domestic sows, this babirusa recovered completely with aggressive management, including antibiotics and supportive care. PMID- 26667560 TI - CLINICOPATHOLOGIC CORRELATES OF FASCIOLIASIS IN TWO EASTERN GREY KANGAROOS (MACROPUS GIGANTEUS). AB - Infection with the introduced trematode Fasciola hepatica was associated with anemia, mild to moderate azotemia, hypoalbuminemia, and elevated liver enzymes and creatine kinase values in two free-ranging eastern grey kangaroos (Macropus giganteus). Both kangaroos were euthanized because of the severity of clinical signs associated with infection. Histopathologic changes included severe cholangiohepatitis, biliary hyperplasia, and fibrosis. Hepatic, splenic, and intestinal amyloidosis was present in one kangaroo and hepatic abscessation in the other; neither histologic change has been reported in macropodids with fascioliasis previously. PMID- 26667561 TI - CIRCULAR EXTERNAL FIXATOR PLACEMENT FOR REPAIR OF AN OPEN DISTAL TARSOMETATARSAL FRACTURE IN AN AFRICAN SACRED IBIS (THRESKIORNIS AETHIOPICUS). AB - An adult male African sacred ibis (Threskiornis aethiopicus) was diagnosed with an open right distal tarsometatarsal fracture on physical examination and radiographs. External coaptation in the form of an L splint failed to stabilize the fracture appropriately and additional fixation options were explored. The location of the fracture near the articulation between the tarsometatarsus and the hallux, the short distal fracture segment, and decreased viability of the foot precluded the use of previously described fixation methods for tarsometatarsal fracture repair. A three-ring external fixator system with modification to the distal-most ring allowed for postoperative weight-bearing with minimal nursing care. The fixator was removed after 41 days, and the bird remained fully weight-bearing. The use of a circular external fixator for distal tarsometatarsal repair in long-legged birds may be a viable option when full return to function with minimal postoperative care is desired. PMID- 26667562 TI - MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS). AB - A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah. PMID- 26667563 TI - CONTROLLING ANTLER GROWTH IN A CASTRATED INDOCHINESE SIKA DEER CERVUS NIPPON PSEUDAXIS USING A COMMERCIALLY AVAILABLE TRENBOLONE ACETATE AND ESTRADIOL IMPLANT. AB - A captive Indochinese sika deer (Cervus nippon pseudaxis) was castrated at the age of 5 yr. The resultant abnormal antler growth over the next few years became difficult to manage from both the veterinary and husbandry standpoints. Using a commercially available trenbolone acetate and estradiol implant marketed for domestic cattle heifers, normal mineralization of the abnormal antlers was achieved along with the expected normal casting. The deer was then maintained for 6 yr using an annual implant regimen. PMID- 26667565 TI - CLINICAL CHALLENGE: DIAGNOSIS OF CONGENITAL KYPHOSIS VIA COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING IN AN ORANGUTAN (PONGO PYGMAEUS). PMID- 26667564 TI - MYCOBACTERIUM GENAVENSE IN AN AFRICAN PENGUIN (SPHENISCUS DEMERSUS). AB - A 19-yr-old female African penguin (Spheniscus demersus) presented with labored breathing and anorexia. Radiographs revealed soft-tissue density lesions in the left lung fields and fluid in the right. The penguin died during the night. Postmortem examination demonstrated multiple granulomas in the lungs and air sacs. The right coelom was filled with opaque fluid. Histopathology of the lung, liver, kidney, and spleen identified Mycobacterium as a primary disease etiology. Large numbers of acid fast-positive, rod-shaped bacteria were recognized on tissue staining. Mycobacterium genavense was detected by polymerase chain reaction (PCR) using primers specific for the species. Further confirmation of M. genavense was accomplished using PCR with universal Mycobacterium spp. primers followed by sequencing of the amplicon obtained. To our knowledge, this is the first reported case of mycobacteriosis-and specifically M. genavense -in an African penguin. This case also demonstrates the similarities of presentation between the more commonly suspected and encountered aspergillosis and mycobacteriosis. PMID- 26667572 TI - Cell Association in Rous Sarcoma Virus (RSV) Rescue and Cell Infection. AB - In my article I tried to present the results of early experiments suggesting a significant role for cell association in Rous sarcoma virus transformation of non permissive cells and revealing that infectious virus can be efficiently rescued from such cells by their fusion with permissive chicken fibroblasts. PMID- 26667573 TI - Prorenin Receptor Homologue VHA-20 is Critical for Intestinal pH Regulation, Ion and Water Management and Larval Development in C. elegans. AB - The prorenin receptor (ATP6AP2) is a multifunctional transmembrane protein; it is a constituent of proton-translocating V-ATPase, a non-proteolytic activator of renin and an adaptor in the Wnt/beta-catenin pathway. Here, we studied vha-20, one of the two prorenin receptor homologues that are identified by sequence similarity in the C. elegans genome. We show that vha-20 (R03E1.2) is prominently expressed in the intestine, in the excretory cell and in amphid neurons, tissues critical for regulation of ion and water management. The expression of vha-20 in the intestine is dependent on NHR-31, a nuclear receptor related to HNF4. VHA-20 is indispensable for normal larval development, acidification of the intestine, and is required for nutrient uptake. Inhibition of vha-20 by RNAi leads to complex deterioration of water and pH gradients at the level of the whole organism including distention of pseudocoelome cavity. This suggests new roles of prorenin receptor in the regulation of body ion and water management and in acidification of intestinal lumen in nematodes. PMID- 26667574 TI - Real-Time PCR Identification of Unique Bacillus anthracis Sequences. AB - Bacillus anthracis is a spore-forming, Gram-positive microorganism. It is a causative agent of anthrax, a highly infectious disease. It belongs to the "Bacillus cereus group", which contains other closely related species, including Bacillus cereus, Bacillus thuringiensis, Bacillus mycoides, Bacillus weihenstephanensis, and Bacillus pseudomycoides. B. anthracis naturally occurs in soil environments. The BA5345 genetic marker was used for highly specific detection of B. anthracis with TaqMan probes. The detection limit of a real-time PCR assay was estimated at the level of 16.9 copies (CI95% - 37.4 to 37.86, SD = 0.2; SE = 0.118). Oligonucleotides designed for the targeted sequences (within the tested locus) revealed 100 % homology to B. anthracis strain reference sequences deposited in the database (NCBI) and high specificity to all tested B. anthracis strains. Additional in silico analysis of plasmid markers pag and cap genes with B. anthracis strains included in the database was carried out. Our study clearly indicates that the BA5345 marker can be used with success as a chromosomal marker in routine identification of B. anthracis; moreover, detection of plasmid markers indicates virulence of the examined strains. PMID- 26667575 TI - Characterization of Porcine Granulosa Cell Line AVG-16. AB - Commercially available, but not yet characterized, the AVG-16 granulosa cell line was established from granulosa cells of medium porcine follicles. To examine the suitability of the AVG-16 cell line for studying the molecular mechanism of action of various environmental oestrogens, we investigated: 1/ cell morphology (by standard haematoxylin and eosin (HE) staining); 2/ basal and follicle stimulating hormone (FSH) or luteinizing hormone (LH)-stimulated steroid hormone (progesterone; P4 and 17beta-oestradiol; E2) secretion (by radioimmunoassay) and 3/ expression of receptors involved in the regulation of granulosa cell function: FSH receptor (FSHR), LH receptor (LHR), oestrogen receptor alpha (ERalpha), oestrogen receptor beta (ERbeta) and aryl hydrocarbon receptor (AhR). mRNA and protein expression was determined by RT-PCR and fluorescence immunocytochemistry, respectively. The secretion of P4 and E2 by AVG-16 cells was in the range of steroid hormone secretion by porcine cultured primary granulosa cells. Neither FSH (100 ng/ml) nor LH (100 ng/ml) affected P4 and E2 secretion by AVG-16 cells. The presence of FSHR and LHR at both mRNA and protein level was not demonstrated in the cells. However, AVG-16 cells were found to express mRNA and protein of ERalpha, ERbeta and AhR. The results of our study showed that AVG-16 cells possess the capability of steroid hormone production, and both oestrogen receptors and AhR are present in these cells. Therefore, AVG-16 cells may serve as an unlimited source of homogenous porcine granulosa cells useful for studying the effects of environmental oestrogens on ovarian physiology. PMID- 26667576 TI - Triptolide Induces Apoptosis and Synergizes with Cisplatin in Cisplatin-Resistant HNE1/DDP Nasopharyngeal Cancer Cells. AB - The purpose of the study was to evaluate the anti-tumour effects of triptolide (TPL) and of the combination of TPL and cisplatin (DDP) in DDPresistant HNE1/DDP nasopharyngeal cancer (NPC) cells and to reveal the possible mechanisms. HNE1/ DDP cells were treated with TPL and/or DDP. Cell proliferation was examined by 3 (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay and colony-forming assay; the combination index of the synergism between TPL and DDP was calculated. Cell morphological changes were observed under a microscope. Reactive oxygen species (ROS) and apoptosis rate were determined by flow cytometry. 5,5',6,6'-tetrachloro-1,1',3,3'-tetrethyl benzimidalyl carbocyanine iodide (JC-1) staining was used to determine mitochondrial membrane potential (MMP). Protein expression was analysed by Western blot, including Bax, caspase-9, Bcl-2, Mcl-1. TPL had an obvious anti-tumour effect and exhibited synergistic cytotoxicity with DDP on DDP-resistant HNE1/DDP cells. TPL induced HNE1/DDP cell apoptosis via inducing ROS generation. This effect was abolished by the inhibitor of ROS, N-acetyl-L-cysteine (NAC). TPL alone or combined with DDP could lower MMP significantly. Western blot showed that TPL alone or in combination with DDP increased expression of Bax and caspase-9, but reduced expression of Bcl-2 and Mcl-1. We conclude that TPL could induce cell apoptosis and synergize with DDP by regulating ROS generation and mitochondrial pathways in HNE1/DDP cells. This indicates that TPL may be effective in DDP-resistant NPC, either alone or combined with DDP. PMID- 26667577 TI - Release of nanomaterials from solid nanocomposites and consumer exposure assessment - a forward-looking review. AB - The European chemical legislation requires manufacturers and importers of chemicals to do consumer exposure assessment when the chemical has certain hazards associated to it (e.g. explosive, carcinogenicity, and hazardous to the aquatic environment), but the question is how this obligation can be met in light of the scientific uncertainty and technical challenges related to exposure assessment of nanomaterials. In this paper, we investigate to what extent the information and data in the literature can be used to perform consumer exposure assessment according to the REACH requirements and we identify and discuss the key data needs and provide recommendations for consumer exposure assessment of nanomaterials. In total, we identified 76 studies of relevance. Most studies have analyzed the release of Ag and TiO2 from textiles and paints, and CNT and SiO2 from nanocomposites. Less than half of the studies report their findings in a format that can be used for exposure assessment under REACH, and most do not include characterization of the released particles. Although inhalation, dermal, and oral exposures can be derived using the guidelines on how to complete consumer exposure assessments under REACH, it is clear that the equations are not developed to take the unique properties of nanomaterials into consideration. Future research is therefore needed on developing more generalized methods for representing nanomaterial release from different product groups at relevant environmental conditions. This includes improving the analytical methods for determining nanomaterial alteration and transformation, as well as quantification, which could subsequently lead to more nano-specific consumer exposure assessment models. PMID- 26667578 TI - Virtual reconstruction of the Early Pleistocene mandible ATD6-96 from Gran Dolina TD6-2 (Sierra De Atapuerca, Spain). AB - OBJECTIVES: In this report, we present a further study of the late Early Pleistocene ATD6-96 human mandible, recovered from the TD6-2 level of the Gran Dolina cave site (Sierra de Atapuerca, northern Spain) and attributed to Homo antecessor. METHODS: ATD6-96 consists of a left half of a gracile mandible of an adult individual with the premolars and molars in place that is broken at the level of the lateral incisor-canine septum. The present analysis is based on a virtual reconstruction of the whole mandible by means of computed tomography (CT). We have reconstructed the symphysis using information from a modern human sample, as well as from a wide sample composed of several Homo specimens. RESULTS: This research has allowed us to record new variables with taxonomic and phylogenetic interest. We have estimated the length/width index of the alveolar arcade, as well as the percentage of the arcade length with regard to the total length. The latter confirms that ATD6-96 shares with all African and Asian Homo species a primitive structural pattern, as it was established in previous studies. In constrast, the length/width index of the alveolar arcade in the H. antecessor specimen is close to the mean values of Neandertals and the Atapuerca Sima de los Huesos hominins. CONCLUSIONS: H. antecessor is derived regarding the shape of the mandibular alveolar arcade within the genus Homo and points to an early divergence from contemporaneous African populations. Our results also ratify the affinities of H. antecessor with Neanderthals, although the precise relationship with this lineage needs further research. PMID- 26667579 TI - Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-kappaB and mitogen-activated protein kinase pathways in mouse macrophages. AB - To elucidate the anti-inflammatory mechanisms involved, we investigated the effects of atractylenolide III (ATL-III) on cytokine expression, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (p38), C-Jun-N-terminal protein kinase1/2 (JNK1/2) and nuclear factor-kappaB (NF kappaB) pathways in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages. Macrophages were incubated with various concentrations (0, 25, 50, 100 MUM) of ATL-III and/or LPS (1 MUg/mL) for 24 h. The production of nitric oxide (NO) was determined by the Greiss reagent. The production of tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and interleukin 6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, macrophages were treated with ATL-III (0, 25, 100 MUM) for 1 h and then stimulated by LPS. NF-kappaB, p38, JNK1/2 and ERK1/2 were determined by western blotting. We found ATL-III showed no inhibitory effect on cell proliferation at concentrations ranging from 1 MUM to 100 MUM. In addition, ATL-III decreased the release of NO, TNF-alpha, PGE2 and IL 6 in a dose-dependent manner and showed statistically significant at concentrations of 50 MUM and 100 MUM as well as cyclooxygenase-2 (COX-2) expression. Furthermore, ATL-III suppressed the transcriptional activity of NF kappaB. ATL-III also inhibited the activation of ERK1/2, p38 and JNK1/2 in LPS treated macrophages and showed statistically significant at concentrations of 25 MUM and 100 MUM. These data suggest that ATL-III shows an anti-inflammatory effect by suppressing the release of NO, PGE2, TNF-alpha and IL-6 related to the NF-kappaB- and MAPK-signaling pathways. PMID- 26667580 TI - Manipulation of Dirac Cones in Mechanical Graphene. AB - Recently, quantum Hall state analogs in classical mechanics attract much attention from topological points of view. Topology is not only for mathematicians but also quite useful in a quantum world. Further it even governs the Newton's law of motion. One of the advantages of classical systems over solid state materials is its clear controllability. Here we investigate mechanical graphene, which is a spring-mass model with the honeycomb structure as a typical mechanical model with nontrivial topological phenomena. The vibration spectrum of mechanical graphene is characterized by Dirac cones serving as sources of topological nontriviality. We find that the spectrum has dramatic dependence on the spring tension at equilibrium as a natural control parameter, i.e., creation and annihilation of the Dirac particles are realized as the tension increases. Just by rotating the system, the manipulated Dirac particles lead to topological transition, i.e., a jump of the "Chern number" occurs associated with flipping of propagating direction of chiral edge modes. This is a bulk-edge correspondence governed by the Newton's law. A simple observation that in-gap edge modes exist only at the fixed boundary, but not at the free one, is attributed to the symmetry protection of topological phases. PMID- 26667581 TI - Benzodi(pyridothiophene): a novel acceptor unit for application in A1-A-A1 type photovoltaic small molecules. AB - A series of novel A1-A-A1 type small molecules (SMs) of BDPT-2BT, BDPT-2FBT and BDPT-2DPP were designed and synthesized, in which benzodi(pyridothiophene) (BDPT) was used as a novel weak central acceptor (A) unit, and benzothiadiazole (BT), fluorinated benzothiadiazole (FBT) and diketopyrrolopyrrole (DPP) were used as terminal acceptor (A1) units, respectively. The pentacyclic BDPT aromatic unit can form big conjugated and planar SMs with the A1 unit, resulting in enhanced pi pi stacking and crystallinity. The effect of the A1 unit on the optical, electrochemical and photovoltaic properties of three SMs was observed. The broader absorption spectrum, lower HOMO energy level, higher photo-response efficiency and better photovoltaic properties were exhibited for BDPT-2DPP. A maximum PCE of 3.97% with a Voc of 0.84 V, a Jsc of 9.0 mA cm(-2) and a FF of 52.37% was obtained in the BDPT-2DPP/PC71BM-based solar cells, which is 1.8 and 1.5 times the values of the BDPT-2BT and BDPT-2FBT-based cells, respectively. PMID- 26667583 TI - Tracking molecular resonance forms of donor-acceptor push-pull molecules by single-molecule conductance experiments. AB - The ability of molecules to change colour on account of changes in solvent polarity is known as solvatochromism and used spectroscopically to characterize charge-transfer transitions in donor-acceptor molecules. Here we report that donor-acceptor-substituted molecular wires also exhibit distinct properties in single-molecule electronics under the influence of a bias voltage, but in absence of solvent. Two oligo(phenyleneethynylene) wires with donor-acceptor substitution on the central ring (cruciform-like) exhibit remarkably broad conductance peaks measured by the mechanically controlled break-junction technique with gold contacts, in contrast to the sharp peak of simpler molecules. From a theoretical analysis, we explain this by different degrees of charge delocalization and hence cross-conjugation at the central ring. Thus, small variations in the local environment promote the quinoid resonance form (off), the linearly conjugated (on) or any form in between. This shows how the conductance of donor-acceptor cruciforms is tuned by small changes in the environment. PMID- 26667584 TI - Frequency and temporal profile of recanalization after cerebral vein and sinus thrombosis. AB - BACKGROUND AND PURPOSE: The temporal course of recanalization and its association with clinical outcome were analysed in our patients with cerebral sinus and/or venous thrombosis (CSVT) and follow-up magnetic resonance imaging (MRI). METHODS: Between January 1998 and September 2014 all patients from our institutions with CSVT were systematically analysed. Baseline data, treatment characteristics and follow-up MRI were retrospectively recorded. The status of recanalization was assessed as complete (CRec), partial (PRec) or failed recanalization. Clinical follow-up was measured with the modified Rankin Scale. Excellent outcome was defined as modified Rankin Scale 0-1. RESULTS: Ninety-nine patients were identified; 97% of these patients were treated with oral anticoagulation (OAC) and the median (min-max) time of OAC was 7 months (1-84). CRec was achieved in 57.6% (57/99), PRec in 29.3% (29/99) and only 13 (13.1%) patients did not recanalize. The median (min-max) time to PRec was 4 months (0.25-14) and to CRec 6 months (2-34). Median time to last clinical follow-up was 8 months (1-88); 91.8% (89/99) had an excellent outcome at last clinical follow-up and only 2.1% (2/99) died. Only thrombosis of the superior sagittal sinus was independently associated with successful recanalization (odds ratio 16, 95% confidence interval 2-138). No severe haemorrhagic complications and no recurrence of CSVT occurred within clinical follow-up. No association of outcome and recanalization status was found. CONCLUSIONS: The recanalization rate of CSVT under OAC was high and the median time to CRec was 6 months. Thrombosis of the superior sagittal sinus is a positive predictor of recanalization. Outcome in this cohort was excellent but no significant association of outcome and recanalization status was found. PMID- 26667586 TI - Effects of Toxic Leachate from Commercial Plastics on Larval Survival and Settlement of the Barnacle Amphibalanus amphitrite. AB - Plastic pollution represents a major and growing global problem. It is well-known that plastics are a source of chemical contaminants to the aquatic environment and provide novel habitats for marine organisms. The present study quantified the impacts of plastic leachates from the seven categories of recyclable plastics on larval survival and settlement of barnacle Amphibalanus (=Balanus) amphitrite. Leachates from plastics significantly increased barnacle nauplii mortality at the highest tested concentrations (0.10 and 0.50 m(2)/L). Hydrophobicity (measured as surface energy) was positively correlated with mortality indicating that plastic surface chemistry may be an important factor in the effects of plastics on sessile organisms. Plastic leachates significantly inhibited barnacle cyprids settlement on glass at all tested concentrations. Settlement on plastic surfaces was significantly inhibited after 24 and 48 h, but settlement was not significantly inhibited compared to the controls for some plastics after 72-96 h. In 24 h exposure to seawater, we found larval toxicity and inhibition of settlement with all seven categories of recyclable commercial plastics. Chemical analysis revealed a complex mixture of substances released in plastic leachates. Leaching of toxic compounds from all plastics should be considered when assessing the risks of plastic pollution. PMID- 26667587 TI - Near-Threshold Photodetachment Cross Section of (SF6)(n)(-) Cluster Anions: The Ion Core Structure. AB - Photodetachment cross sections as a function of photon energy are measured for cold (SF6)n(-) cluster anions stored in an electrostatic ion beam trap. Absolute photodetachment cross sections near the adiabatic limit are reported. The strong dependence of the SF6(-) absolute photodetachment cross section on the anion equilibrium bond length leads to the conclusion that the excess charge is localized on a SF6(-) ion core that is only subtly perturbed by the neighboring cluster units. PMID- 26667589 TI - Harnessing Hierarchical Nano- and Micro-Fabrication Technologies for Musculoskeletal Tissue Engineering. AB - Cells within a tissue are able to perceive, interpret and respond to the biophysical, biomechanical, and biochemical properties of the 3D extracellular matrix environment in which they reside. Such stimuli regulate cell adhesion, metabolic state, proliferation, migration, fate and lineage commitment, and ultimately, tissue morphogenesis and function. Current scaffold fabrication strategies in musculoskeletal tissue engineering seek to mimic the sophistication and comprehensiveness of nature to develop hierarchically assembled 3D implantable devices of different geometric dimensions (nano- to macrometric scales) that will offer control over cellular functions and ultimately achieve functional regeneration. Herein, advances and shortfalls of bottom-up (self assembly, freeze-drying, rapid prototype, electrospinning) and top-down (imprinting) scaffold fabrication approaches, specific to musculoskeletal tissue engineering, are discussed and critically assessed. PMID- 26667588 TI - A single amino acid substitution in the R3 domain of GLABRA1 leads to inhibition of trichome formation in Arabidopsis without affecting its interaction with GLABRA3. AB - GLABRA1 (GL1) is an R2R3 MYB transcription factor that regulates trichome formation in Arabidopsis by interacting with the bHLH transcription factor GLABRA3 (GL3) or ENHANCER OF GL3 (EGL3). The conserved [D/E]L*2 [R/K]*3L*6L*3R amino acid signature in the R3 domain of MYB proteins has been shown to be required for the interaction of MYBs with R/B-like bHLH transcription factors. By using genetic and molecular analyses, we show that the glabrous phenotype in the nph4-1 mutant is caused by a single nucleotide mutation in the GL1 gene, generating a Ser to Phe substitution (S92F) in the conserved [D/E]L*2[R/K]*3L*6L*3R amino acid signature of GL1. Activation of the integrated GL2p:GUS reporter gene in protoplasts by cotransfection of GL1 and GL3 or EGL3 was abolished by this GL1-S92F substitution. However, GL1-S92F interacted successfully with GL3 or EGL3 in protoplast transfection assays. Unlike VPGL1GL3, the fusion protein VPGL1-S92FGL3 failed to activate the integrated GL2p:GUS reporter gene in transfected protoplasts. These results suggested that the S92 in the conserved [D/E]L*2 [R/K]*3L*6L*3R amino acid signature of GL1 is not essential for the interaction of GL1 and GL3, but may play a role in the binding of GL1 to the promoters of its target genes. PMID- 26667590 TI - Intravascular Ultrasound Guidance vs. Angiographic Guidance in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction - Long-Term Clinical Outcomes From the CREDO-Kyoto AMI Registry. AB - BACKGROUND: In the setting of elective percutaneous coronary intervention (PCI), intravascular ultrasound (IVUS)-guided PCI is associated with a reduction in the incidence of target vessel revascularization (TVR), but the impact of IVUS on long-term clinical outcome in the setting of emergency PCI for ST-segment elevation acute myocardial infarction (STEMI) is still unclear. METHODS AND RESULTS: The subjects consisted of 3,028 STEMI patients who underwent primary PCI within 24 h of symptom onset in the CREDO-Kyoto acute myocardial infarction registry. Of these, 932 patients (31%) underwent IVUS-guided PCI. Compared with the angiography-guided PCI without IVUS, IVUS-guided PCI was associated with significantly lower incidences of TVR (primary outcome measure; 22% vs. 27%, log rank P<0.001) and definite stent thrombosis (ST; 1.2% vs. 3.1%, log-rank P=0.003). The cumulative incidence of all-cause death was not significantly different between the 2 groups. After adjusting for confounders, however, there were no significant differences between the 2 groups in risk for TVR (adjusted HR, 1.14; 95% CI: 0.86-1.51, P=0.38) and definite ST (adjusted HR, 0.58; 95% CI: 0.19-1.72, P=0.33). CONCLUSIONS: IVUS-guided PCI was not associated with a lower risk for TVR or ST in STEMI patients undergoing primary PCI. PMID- 26667591 TI - Predictors of Worsening Renal Function in Patients With Acute Decompensated Heart Failure Treated by Low-Dose Carperitide. AB - BACKGROUND: Predictors of worsening renal function (WRF: increase in serum creatinine >= 0.3 mg/dl from the value on admission) in patients with acute decompensated heart failure (ADHF) treated by low-dose carperitide (0.01-0.05 MUg/kg/min) are unclear. METHODS AND RESULTS: We retrospectively investigated predictors of WRF within the first 24 h of low-dose carperitide therapy in 205 patients (mean age, 75.6 +/- 12.1 years) hospitalized for ADHF and treated with low-dose carperitide between January 2006 and April 2014. WRF occurred in 14 patients (7%). A multivariate adjustment analysis showed that independent predictors of WRF within 24 h were hypotension (systolic blood pressure <90 mmHg) within 12 h (odds ratio, 8.7; 95% confidence interval, 2.38-35.88; P=0.0012) and serum creatinine on admission (odds ratio, 3.64; 95% confidence interval, 1.84 7.67; P=0.0003). In patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), the rate of WRF occurrence was higher in those complicated by hypotension than in those without hypotension (22.6% [7/31 patients] vs. 4.4% [5/113 patients], P=0.0041). In contrast, in patients with eGFR >= 60 ml/min/1.73 m(2), hypotension did not influence the occurrence of WRF (0% [0/9 patients] vs. 3.9% [2/51 patients], P=NS). CONCLUSIONS: Hypotension within 12 h and renal dysfunction on admission are independent predictors of WRF within 24 h in patients with ADHF treated by low-dose carperitide. Hypotension may not cause WRF in patients with eGFR >= 60 ml/min/1.73 m(2). PMID- 26667592 TI - Lewy Bodies and the Mechanisms of Neuronal Cell Death in Parkinson's Disease and Dementia with Lewy Bodies. AB - Neuronal loss in specific brain regions and neurons with intracellular inclusions termed Lewy bodies are the pathologic hallmark in both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Lewy bodies comprise of aggregated intracellular vesicles and proteins and alpha-synuclein is reported to be a major protein component. Using human brain tissue from control, PD and DLB and light and confocal immunohistochemistry with antibodies to superoxide dismutase 2 as a marker for mitochondria, alpha-synuclein for Lewy bodies and betaIII Tubulin for microtubules we have examined the relationship between Lewy bodies and mitochondrial loss. We have shown microtubule regression and mitochondrial and nuclear degradation in neurons with developing Lewy bodies. In PD, multiple Lewy bodies were often observed with alpha-synuclein interacting with DNA to cause marked nuclear degradation. In DLB, the mitochondria are drawn into the Lewy body and the mitochondrial integrity is lost. This work suggests that Lewy bodies are cytotoxic. In DLB, we suggest that microtubule regression and mitochondrial loss results in decreased cellular energy and axonal transport that leads to cell death. In PD, alpha-synuclein aggregations are associated with intact mitochondria but interacts with and causes nuclear degradation which may be the major cause of cell death. PMID- 26667593 TI - Rapid extraction and determination of 25 bioactive constituents in Alpinia oxyphylla using microwave extraction with ultra high performance liquid chromatography with tandem mass spectrometry. AB - A novel and rapid microwave extraction and ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of 25 bioactive constituents (including two new constituents) in Fructus Alpinia oxyphylla. The optimized conditions of the microwave extraction was a microwave power of 300 W, extraction temperature of 80 degrees C, solvent-to-solid ratio of 30 mL/g and extraction time of 8 min. Separation was achieved on a Waters ACQUITY UPLC((r)) HSS C18 column (2.1 mm* 50 mm, 1.8 MUm) using gradient elution with a mobile phase consisting of acetonitrile and 1 mM ammonium acetate at a flow rate of 0.2 mL/min. This is the first report of the simultaneous determination of 25 bioactive constituents in Fructus Alpinia oxyphylla by ultra high performance liquid chromatography with tandem mass spectrometry. The method was validated with good linearity, acceptable precision and accuracy. The validated method was successfully applied to determine the contents of 25 bioactive constituents in Fructus Alpinia oxyphylla from different sources and the analysis results were classified by hierarchical cluster analysis, which indicated the effect of different cultivation regions on the contents of constituents. This study provides powerful and practical guidance in the quality control of Alpinia oxyphylla and lays the foundation for further research of Alpinia oxyphylla. PMID- 26667594 TI - Exercise and the immune system: implications for elite athletes and the general population. PMID- 26667595 TI - Safety and efficiency of ultrasound-guided intermediate cervical plexus block for carotid surgery. AB - OBJECTIVE: Since stroke and myocardial ischaemia are major causes of perioperative morbidity and mortality associated with carotid endarterectomy, monitoring the brain and ensuring the best haemodynamic stability are important goals of the management. As regional anaesthesia was reported to improve haemodynamic stability during carotid endarterectomy (CEA), we conducted a prospective observational study on the efficacy and safety of ultrasound-guided intermediate cervical plexus blocks (CPB), with early (immediate postoperative) and mid-term (day 30) outcomes in awake patients undergoing CEA. METHODS: After the ethics committee approval, 50 patients undergoing a carotid endarterectomy with CPB from April 2011 to May 2013 were included. Anaesthesia and surgical dissection parameters, early complications and haemodynamic stability were recorded, as well as neurologic and cardiac outcomes initially and one month later. RESULTS: Cervical space was easy to locate by ultrasound in 90% of the patients. The quality of anaesthesia and surgical dissection was good in 86 and 88% of patients, respectively. No conversion to GA was required, secondary to a lack of analgesia. Two patients (4%) had severe hypotension (<100mmHg). Three patients required a shunt after carotid clamping for loss of consciousness with a favourable neurological outcome. We observed one elevation of cTnI (0.95ng.ml( 1)) without ECG change and 1 death occurred after a postoperative haemorrhagic stroke. CONCLUSIONS: The present work reports our first 50 cases of intermediate CPB using ultrasound guidance. The results underline that this technique is easy to perform, safe and reliable, provided good surgical conditions with continuous intraoperative neurologic monitoring and stable haemodynamics are respected. PMID- 26667596 TI - Cross-talk phenomenon during femoral transpulmonary thermodilution in a critically ill patient. PMID- 26667598 TI - The RpfB-Dependent Quorum Sensing Signal Turnover System Is Required for Adaptation and Virulence in Rice Bacterial Blight Pathogen Xanthomonas oryzae pv. oryzae. AB - Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, produces diffusible signal factor (DSF) family quorum sensing signals to regulate virulence. The biosynthesis and perception of DSF family signals require components of the rpf (regulation of pathogenicity factors) cluster. In this study, we report that RpfB plays an essential role in DSF family signal turnover in X. oryzae pv. oryzae PXO99A. The production of DSF family signals was boosted by deletion of the rpfB gene and was abolished by its overexpression. The RpfC/RpfG-mediated DSF signaling system negatively regulates rpfB expression via the global transcription regulator Clp, whose activity is reversible in the presence of cyclic diguanylate monophosphate. These findings indicate that the DSF family signal turnover system in PXO99A is generally consistent with that in Xanthomonas campestris pv. campestris. Moreover, this study has revealed several specific roles of RpfB in PXO99A. First, the rpfB deletion mutant produced high levels of DSF family signals but reduced extracellular polysaccharide production, extracellular amylase activity, and attenuated pathogenicity. Second, the rpfB/rpfC double-deletion mutant was partially deficient in xanthomonadin production. Taken together, the RpfB-dependent DSF family signal turnover system is a conserved and naturally presenting signal turnover system in Xanthomonas spp., which plays unique roles in X. oryzae pv. oryzae adaptation and pathogenesis. PMID- 26667597 TI - Baclofen intoxication cases in an intensive care unit. PMID- 26667599 TI - Paradoxical exacerbation of chronic plaque psoriasis by sorafenib. AB - Vascular endothelial growth factor (VEGF) antagonists have been investigated as a potential treatment for psoriasis, but there have been reports of VEGF antagonists triggering and/or exacerbating pre-existing psoriasis. We present the case of a 61-year old-man with exacerbation of pre-existing psoriasis after treatment with sorafenib, a small molecule inhibitor of the tyrosine kinase domain of the VEGF receptor, and we review the literature for other published cases of sorafenib-induced or sorafenib-exacerbated psoriasis. Clinicians, including both dermatologists and oncologists, should be aware of this potential side-effect of sorafenib in addition to the other cutaneous side effects reported for this drug. PMID- 26667601 TI - The FDA's sentinel initiative--A comprehensive approach to medical product surveillance. AB - In May 2008, the Department of Health and Human Services announced the launch of the Sentinel Initiative by the US Food and Drug Administration (FDA) to create the Sentinel System, a national electronic system for medical product safety surveillance. This system complements existing FDA surveillance capabilities that track adverse events reported after the use of FDA regulated products by allowing the FDA to proactively assess the safety of these products. PMID- 26667600 TI - Phase-cycled simultaneous multislice balanced SSFP imaging with CAIPIRINHA for efficient banding reduction. AB - PURPOSE: To present a time-efficient technique for banding reduction in balanced steady-state free precession (bSSFP) imaging using phase-cycled simultaneous multislice (SMS) acquisition with CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration). THEORY: The proposed technique exploits the inherent phase modulation of SMS imaging with CAIPIRINHA to acquire multiple phase-cycled images, which can be combined for efficient banding reduction within the same scan time of a single-band bSSFP scan. METHODS: Bloch equation simulation, phantom and in vivo brain, abdominal and cardiac imaging experiments were performed on healthy volunteers at 3T using multi-channel head and body array coils with SMS acceleration factors of two to four. The performance of banding reduction was quantitatively evaluated based on the percent ripple of signal distribution and signal-to-noise ratio (SNR) efficiency in both phantom and human studies. RESULTS: The banding artifact was successfully removed or suppressed using phase-cycled SMS bSSFP imaging across SMS factors of two to four. The performance of banding reduction improved with higher SMS factors along with increased SNR efficiency. CONCLUSION: Phase-cycled SMS bSSFP with CAIPIRINHA is a promising technique for efficient band reduction in bSSFP without prolonged scan time. Further evaluation of this technique in clinical applications is warranted. Magn Reson Med 76:1764-1774, 2016. (c) 2015 International Society for Magnetic Resonance in Medicine. PMID- 26667602 TI - Comprehensive study of liposome-assisted synthesis of membrane proteins using a reconstituted cell-free translation system. AB - Membrane proteins play pivotal roles in cellular processes and are key targets for drug discovery. However, the reliable synthesis and folding of membrane proteins are significant problems that need to be addressed owing to their extremely high hydrophobic properties, which promote irreversible aggregation in hydrophilic conditions. Previous reports have suggested that protein aggregation could be prevented by including exogenous liposomes in cell-free translation processes. Systematic studies that identify which membrane proteins can be rescued from irreversible aggregation during translation by liposomes would be valuable in terms of understanding the effects of liposomes and developing applications for membrane protein engineering in the context of pharmaceutical science and nanodevice development. Therefore, we performed a comprehensive study to evaluate the effects of liposomes on 85 aggregation-prone membrane proteins from Escherichia coli by using a reconstituted, chemically defined cell-free translation system. Statistical analyses revealed that the presence of liposomes increased the solubility of >90% of the studied membrane proteins, and ultimately improved the yields of the synthesized proteins. Bioinformatics analyses revealed significant correlations between the liposome effect and the physicochemical properties of the membrane proteins. PMID- 26667603 TI - Comparison of Elecsys Anti-HCV II Assay With Other HCV Screening Assays. AB - OBJECTIVE: Early detection of hepatitis C virus (HCV) is an important step in preventing progression to cirrhosis and hepatocellular carcinoma. Serologic assays for anti-HCV antibody are valuable first-line tests in the screening and diagnosis of HCV infection. This study's aim was to evaluate the sensitivity and specificity of Elecsys Anti-HCV II assay for HCV screening. DESIGN AND METHODS: A total of 1,044 routine sera, 20 known HCV-positive samples, plus 54 preselected weakly positive samples were tested for anti-HCV with Elecsys Anti-HCV II assay, Elecsys Anti-HCV assays, InTec HCV enzymoimmunoassay (EIA), and Livzon Anti-HCV EIA. Interference test was assessed with additional 423 specimens without clinical evidence of HCV infection: preselected HCV weak reactive samples; dialysis samples; anti-HBc (antibody to HBV core antigen) (+), anti-Treponema pallidum (+), and anti-HIV (+) sera; and samples form autoimmune/alcoholic hepatitis or systemic Lupus erythematosus (SLE). Discrepant results were evaluated with recombinant immunoblot assay. The seroconversion panels were evaluated to assess how early each assay could detect HCV infection. RESULTS: The specificity (99.81%) of the Elecsys Anti-HCV II assay was less than that with the two EIA comparison methods. However, false-negative results were easily seen in the EIA assays. When serial bleeds of HCV panels were compared with the above mentioned methods, the assay detected acute HCV infection only 3.5 days after a positive HCV-RNA nucleic acid test and earlier than the comparator assays. CONCLUSION: Sensitivities and specificities of the anti-HCV assays were sufficiently high for use in this study. The Elecsys Anti-HCV II assay is suitable for screening and reliable early detection of HCV infection. PMID- 26667604 TI - Tracheobronchopathia osteochondroplastica. AB - Tracheobronchopathia osteochondroplastica (TBOC) is a rare disease of the trachea and bronchi characterized by submucosal nodules of osseous and cartilaginous tissue. In this series, we present three cases highlighting the varied clinical presentations of this rare disease process, which ranged from a rough voice to a chronic cough to lobar pneumonia. The disorder may mimic other lesions. We review the clinical presentations, pathophysiology, lab tests, imaging, diagnosis, and management of TBOC patients. Laryngoscope, 126:2006-2009, 2016. PMID- 26667605 TI - Using Electronic Health Records for Population Health Research: A Review of Methods and Applications. AB - The use and functionality of electronic health records (EHRs) have increased rapidly in the past decade. Although the primary purpose of EHRs is clinical, researchers have used them to conduct epidemiologic investigations, ranging from cross-sectional studies within a given hospital to longitudinal studies on geographically distributed patients. Herein, we describe EHRs, examine their use in population health research, and compare them with traditional epidemiologic methods. We describe diverse research applications that benefit from the large sample sizes and generalizable patient populations afforded by EHRs. These have included reevaluation of prior findings, a range of diseases and subgroups, environmental and social epidemiology, stigmatized conditions, predictive modeling, and evaluation of natural experiments. Although studies using primary data collection methods may have more reliable data and better population retention, EHR-based studies are less expensive and require less time to complete. Future EHR epidemiology with enhanced collection of social/behavior measures, linkage with vital records, and integration of emerging technologies such as personal sensing could improve clinical care and population health. PMID- 26667606 TI - A Transdisciplinary Approach to Public Health Law: The Emerging Practice of Legal Epidemiology. AB - Public health law has roots in both law and science. For more than a century, lawyers have helped develop and implement health laws; over the past 50 years, scientific evaluation of the health effects of laws and legal practices has achieved high levels of rigor and influence. We describe an emerging model of public health law that unites these two traditions. This transdisciplinary model adds scientific practices to the lawyerly functions of normative and doctrinal research, counseling, and representation. These practices include policy surveillance and empirical public health law research on the efficacy of legal interventions and the impact of laws and legal practices on health and health system operation. A transdisciplinary model of public health law, melding its legal and scientific facets, can help break down enduring cultural, disciplinary, and resource barriers that have prevented the full recognition and optimal role of law in public health. PMID- 26667607 TI - Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt(-/-) Mouse Model of Preeclampsia/Fetal Growth Restriction. AB - Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT(-/-)) and endothelial nitric oxide synthase (Nos3(-/-)) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT(-/-) mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3(-/-), COMT(-/-) and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3(-/-) and C57BL/6J mice (p < 0.05) and in 18 metabolites between C57BL/6J and COMT(-/-) mice (p < 0.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p < 0.05) remained in COMT(-/-) mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT(-/-) mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action. PMID- 26667609 TI - Will emerging pharmacotherapies improve the management of polycystic ovarian syndrome? PMID- 26667608 TI - Pregnancy outcomes in women with sickle-cell disease in low and high income countries: a systematic review and meta-analysis. AB - BACKGROUND: Pregnancy in women with sickle-cell disease (SCD) is associated with increased adverse outcomes. Findings on the association between SCD and adverse pregnancy outcomes are conflicting, and the results do not address whether these associations are similar in both low- and high-income countries. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate pregnancy outcomes associated with SCD. SEARCH STRATEGY: The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles on pregnancy outcomes in women with SCD. SELECTION CRITERIA: We used full research articles published in English that compared women with SCD with women who did not have SCD, as controls. DATA COLLECTION AND ANALYSIS: Data were abstracted and analysed using comprehensive Meta-analysis 2.2. The primary outcomes were intrauterine growth restriction and perinatal mortality. Secondary outcomes were rates of caesarean sections, pre-eclampsia, eclampsia, postpartum haemorrhage, maternal mortality, prematurity, and low birthweight. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN RESULTS: Sixteen studies met all of the selection criteria and were included in the analysis. SCD was associated with intrauterine growth restriction (pooled OR 2.79, 95% CI 1.85-4.21), perinatal mortality (pooled OR 3.76, 95% CI 2.34-6.06), and low birthweight (pooled OR 2.00, 95% CI 1.42-2.83). SCD was also associated with an increased risk of pre-eclampsia (pooled OR 2.05, 95% CI 1.47-2.85), maternal mortality (pooled OR 10.91, 95% CI 1.83-65.11, P = 0.009), and eclampsia (pooled OR 3.02, 95% CI 1.20-7.58). CONCLUSION: Pregnancy in women with SCD is associated with increased risks of adverse perinatal and maternal outcomes in both low- and high-income countries. TWEETABLE ABSTRACT: This meta-analysis showed worse pregnancy outcomes in women with sickle-cell disease compared with controls. PMID- 26667610 TI - Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands. AB - After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p=0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p=0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease. PMID- 26667611 TI - The confounded effects of age and exposure history in response to influenza vaccination. AB - Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence-the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly. PMID- 26667612 TI - National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance. AB - OBJECTIVES: To assess the quality of national Hospital Episode Statistics (HES) data for intussusception, and evaluate this routinely collected database for rotavirus vaccine safety surveillance by estimating pre-vaccination trends in intussusception hospitalisation. METHODS: Data linkage was performed between HES and prospective intussusception data from the British Paediatric Surveillance Unit (BPSU), followed by capture-recapture analysis to verify HES data quality. Inclusion criteria were infants aged less than 12 months and admitted for intussusception to National Health Service (NHS) hospitals in England from March 2008 to March 2009. To estimate pre-vaccination incidence rates of intussusception, we performed a retrospective analysis of HES data. Infants aged less than 12 months and admitted for intussusception to NHS hospitals in England between 1995 and 2009 were included. RESULTS: Data linkage between 254 cases of intussusception identified in HES data and 190 cases reported via the BPSU resulted in 163 cases common to both data sources. Of remaining 91 cases in HES, 37 had confirmed intussusception. HES data accuracy was 78.7% (200 confirmed/254 cases) and completeness for intussusception was 86% (163 matched/190 BPSU cases) compared to 81.5% (163 matched/200 HES cases) for BPSU. A total of 233 (95% CI: 227.4 to 238.8) intussusception cases were estimated for the infant population (2008 to 2009). For retrospective analysis, of 6462 intussusception admissions in HES data (1995 to 2009), 1594 (24.7%) were duplicate admissions. A declining trend in intussusception incidence was observed in the infant population, from 86/100,000 in 1997 to 34/100,000 in 2009 (60% reduction, P<0.001). Cosinor modelling showed an excess of cases among infants in winter and spring (P<0.001, n=4957, 1995 to 2009). CONCLUSION: National hospital data capture the majority of admissions for intussusception and should be considered for the post implementation surveillance of rotavirus vaccine safety in England. PMID- 26667614 TI - The Number of Trials Required to Obtain a Representative Movement Pattern During a Hurdle Hop Exercise. AB - When reporting a subject's mean movement pattern, it is important to ensure that reported values are representative of the subject's typical movement. While previous studies have used the mean of 3 trials, scientific justification of this number is lacking. One approach is to determine statistically how many trials are required to achieve a representative mean. This study compared 4 methods of calculating the number of trials required in a hopping movement to achieve a representative mean. Fifteen males completed 15 trials of a lateral hurdle hop. Range of motion at the trunk, pelvis, hip, knee, and ankle, in addition to peak moments for the latter 3 joints were examined. The number of trials required was computed using a peak intraclass correlation coefficient method, sequential analysis with a bandwidth of acceptable variance in the mean, and a novel method based on the standard error of measurement (SEMind). The number of trials required across all variables ranged from 2 to 12 depending on method, joint, and anatomical plane. The authors advocate the SEMind method as it demonstrated fewer limitations than the other methods. Using the SEMind, the required number of trials for a representative mean during the lateral hurdle hop is 6. PMID- 26667613 TI - Optimization of physiological properties of hydroxyapatite as a vaccine adjuvant. AB - Various particles such as Alum or silica are known to act as an adjuvant if co administered with vaccine antigens. Several reports have demonstrated that the adjuvanticity is strongly affected by the physicochemical properties of particles such as the size, shape and surface charge, although the required properties and its relationship to the adjuvanticity are still controversial. Hydroxyapatite particle (HAp) composed of calcium phosphate has been shown to work as adjuvant in mice. However, the properties of HAp required for the adjuvanticity have not been fully characterized yet. In this study, we examined the role of size or shape of HAps in the antibody responses after immunization with antigen. HAps whose diameter ranging between 100 and 400 nm provided significantly higher antibody responses than smaller or larger ones. By comparison between sphere and rod shaped HAps, rod shaped HAps induced stronger inflammasome-dependent IL-1beta production than the sphere shaped ones in vitro. However, sphere- and rod-shaped HAp elicited comparable antibody response in WT mice. Vice versa, Nlrp3(-/-), Asc(-/-) or Caspase1(-/-) mice provided comparable level of antibody responses to HAp adjuvanted vaccination. Collectively, our results demonstrated that the size rather than shape is a more critical property, and IL-1beta production via NLRP3 inflammasome is dispensable for the adjuvanticity of HAps in mice. PMID- 26667615 TI - [Approach to patients with liver diseases]. AB - In recent years the most frequent cause of chronic liver diseases in western countries has become Non-alcoholic hepatic steatosis/steatohepatitis (NAFLD/NASH). It is part or immediate manifestation of metabolic syndrome. A crucial task for the future is to diagnose this hepatic injury to a greater extent and cooperate with other internal medicine physicians in the care of patients with NAFLD. It has been clearly proven that it is not a benign disease, as assumed in the past. Non-alcoholic steatohepatitis can have serious consequences for the patient and it needs to be actively searched for. The still prevalent notion that normal liver tests in patients with hepatic steatosis eliminate a more serious liver injury has also been disproved. On the contrary, this condition is common in patients with NAFLD. Also the patients with normal liver test results can have advanced fibrosis/cirrhosis. It is needed to target identification of a liver injury in a patient with the detected metabolic syndrome with the same intensity as the other diabetes complications are searched for today. All patients with type 2 diabetes mellitus (DM2T) should undergo ultrasound examination of the liver and it is further recommended to check the liver tests in annual intervals at least. The cause of liver lesions should be found in all diabetics who had higher liver test values established even once. The liver injury needs to be further regularly followed in these patients. Regarding the patients without the metabolic syndrome anamnesis with the NAFLD signs, it is needed to actively search for the components of the metabolic syndrome (hypertension, dyslipidemia, impaired glucose tolerance, diabetes). PMID- 26667616 TI - [Cirrhosis of the liver and HCV]. AB - Cirrhosis of the liver is the final morphological stage of most liver diseases with subsequent risk of decompensation and complications (portal hypertension, HCC). At present it is apparent, however, that a dynamic two-way process is involved with a possibility of further progression, but also regression of fibrosis/cirrhosis provided that causal treatment of the basic hepatologic disease is possible. Determining the stage and level of fibrosis progression is absolutely key to further care of the patient, establishment of the prognosis and possibly the treatment indication. At present non-invasive methods of liver fibrosis are the preferred option already, (serum, elastography), which for this indication gradually replace a liver biopsy. These methods allow for an exact estimate of the patients prognosis and first of all long-term non-invasive following of the liver disease development. Chronic hepatitis C is one of the most frequent causes of liver cirrhosis. The healing of hepatitis C is essential for the improvement of patients prognosis and reduction of the risk of complications development. In the field of treatment of this disease a pharmacological revolution has taken place in recent years, unprecedented in the other fields of internal medicine. Due to the exact description and understanding of the cycle of virus replication, a number of direct-acting antiviral drugs have been introduced to the clinical practice, which made it possible to remove interferon preparations (numerous adverse effects) from the treatment after 20 years, but first of all they increased the effect of HCV treatment, reaching approx. 95-100 % healed patients after 12 weeks of the combined therapy. These preparations are essentially free from adverse effects and the treatment lasts 12 24 weeks (with an option of its shortening to 8 weeks). Their main disadvantage is their extremely high cost at the present time. PMID- 26667618 TI - Accepted Abstracts. PMID- 26667617 TI - [Possibilities of IFN-free therapy of hepatitis C]. AB - Chronic hepatitis C therapy using Directly Acting Antivirals (DAA) has high efficacy (till 100 %), minimum contra-indications and extraordinarily favorable safety profile. Primarily, it is necessary to pay attention to drug-drug interactions. However they are well documented and successfully resolvable already in general clinical practice. Current possibilities of interferon-free therapy represent combinations of sofosbuvir with other DAA or with ribavirin and combination of paritaprevir boosted by ritonavir+ombitasvir+/-dasabuvir (3D combination). PMID- 26667619 TI - Codifying healthcare--big data and the issue of misclassification. AB - The rise of electronic medical records has led to a proliferation of large observational studies that examine the perioperative period. In contrast to randomized controlled trials, these studies have the ability to provide quick, cheap and easily obtainable information on a variety of patients and are reflective of everyday clinical practice. However, it is important to note that the data used in these studies are often generated for billing or documentation purposes such as insurance claims or the electronic anesthetic record. The reliance on codes to define diagnoses in these studies may lead to false inferences or conclusions. Researchers should specify the code assignment process and be aware of potential error sources when undertaking studies using secondary data sources. While misclassification may be a short-coming of using large databases, it does not prevent their use in conducting meaningful effectiveness research that has direct consequences on medical decision making. PMID- 26667620 TI - Irreducible plantar dislocation of the interphalangeal joint of the great toe due to an accessory sesamoid bone: a case report. AB - INTRODUCTION: Great toe dislocation frequently occurs at the metatarsophalangeal joint. However, an irreducible dislocation of the great toe interphalangeal (IP) joint due to an accessory sesamoid bone is relatively unusual. CASE REPORT: A 23 year-old woman suffered a dislocated IP joint of the left great toe. The distal phalanx was plantar subluxated, and the articular surface was misaligned. Ultrasound, magnetic resonance imaging, and computed tomography images did not indicate any factors inhibiting reduction. In addition, the sesamoid bone at the IP joint was found to be rotated in the long-axis direction. The sesamoid bone of the IP joint was hooked from the distal direction and occupied the intercondylar area. IP joint of the left great toe was flexed and the distal phalanx was pushed toward the proximal phalanx during reduction locking with fluoroscopic guidance under local anesthesia, and the dislocation was successfully reduced. DISCUSSION: The sesamoid bone at the IP joint is anatomically located dorsal to the flexor hallucis longus tendon and volar plate. The sesamoid bone fitted exactly in the distal intercondylar area. The sesamoid bone in our patient could be rotated by forcible plantar flexion of the IP joint displaced proximally and hooked into the intercondylar area from the proximal aspect. Then, the distal phalanx was pulled proximally through the volar plate. This is the first report on a plantar dislocation of the IP joint. PMID- 26667622 TI - Meniscal degeneration in human knee osteoarthritis: in situ hybridization and immunohistochemistry study. AB - OBJECTIVE: Meniscus injury is one of the causes of secondary osteoarthritis (OA). However, the role of meniscus is still unclear. Human meniscal distribution of cells and cartilage oligomeric matrix protein (COMP) and their changes in advanced OA were analyzed. PATIENTS AND METHODS: Thirty-one medial menisci from patients with knee OA that underwent a total knee arthroplasty were studied. Normal meniscal tissue was obtained from partial arthroscopic meniscectomy. Meniscal samples were processed for histology, immunohistochemistry and in situ hybridization, for cell assessment including density, active divisions, apoptosis, COMP distribution and proteoglycan content. RESULTS: Osteoarthritic menisci demonstrated areas of cell depletion and significant decrease in COMP immunostaining. Actively dividing cells were only found in the meniscectomy group, but not in the osteoarthritic group. Proteoglycan staining was less prominent in menisci from the osteoarthritis group. CONCLUSIONS: Our results show a decreased cell population, with low COMP and altered matrix organization in osteoarthritis menisci that suggest an altered meniscal scaffold and potential impairment of meniscal function. These meniscal changes may be associated with the development of knee osteoarthritis. PMID- 26667621 TI - S3-Guideline non-traumatic adult femoral head necrosis. AB - INTRODUCTION: The treatment of adult non-traumatic avascular necrosis of the femoral head (AVN; N-ANFH) within an estimated incidence of 5000-7000 cases per annum in Germany remains a challenge. Risk factors include steroids, alcohol abuse, chemotherapy and immunosuppressive medication, but a genetic predisposition has been suggested. Early diagnosis of this often bilateral disease process is essential for successful conservative or joint preserving surgical management. In this review, we present the update German consensus S3 guideline "diagnosis and management for N-ANFH" as a concise summary. MATERIALS AND METHODS: This systematic review is based on the published literature from January 1, 1970 to April 31, 2013 (German and English language). Inclusion criteria were systematic reviews, meta-analyses and relevant peer review publications. We identified a total of 3715 related publications, of which 422 were suitable according to the SIGN criteria, but only 159 fulfilled our inclusion criteria. RESULTS AND CONCLUSIONS: Clinical suspicion of N-ANFH mandates radiographic evaluation. If radiographs are normal MRI scans are recommended, which should be evaluated according to the ARCO-classification. Differential diagnoses include transient osteoporosis, bone bruise, insufficiency fracture and destructive arthropathy. Untreated, subchondral fractures commonly occur within 2 years, during which the risk for contralateral involvement is high thereafter unlikely. Conservative management with Ilomedin and Alendronat can be tried, but other pharmacological or physical treatments are inappropriate. No specific joint preserving procedure can be recommended, but core decompression should be considered in early stages if necrosis is <30 %. In ARCO stages IIIc or IV total hip arthroplasty (THA) should be contemplated, which offers similar outcome compared to osteoarthritis. Young age is the main risk factor for higher revision rates after THA for N-ANFH. PMID- 26667623 TI - Membrane-associated collagens with interrupted triple-helices (MACITs): evolution from a bilaterian common ancestor and functional conservation in C. elegans. AB - BACKGROUND: Collagens provide structural support and guidance cues within the extracellular matrix of metazoans. Mammalian collagens XIII, XXIII and XXV form a unique subgroup of type II transmembrane proteins, each comprising a short N terminal cytosolic domain, a transmembrane domain and a largely collagenous ectodomain. We name these collagens as MACITs (Membrane-Associated Collagens with Interrupted Triple-helices), and here investigate their evolution and conserved properties. To date, these collagens have been studied only in mammals. Knowledge of the representation of MACITs in other extant metazoans is lacking. This question is of interest for understanding structural/functional relationships in the MACIT family and also for insight into the evolution of MACITs in relation to the secreted, fibrillar collagens that are present throughout the metazoa. RESULTS: MACITs are restricted to bilaterians and are represented in the Ecdysozoa, Hemichordata, Urochordata and Vertebrata (Gnathostomata). They were not identified in available early-diverging metazoans, Lophotrochozoa, Echinodermata, Cephalochordata or Vertebrata (Cyclostomata). Whereas invertebrates encode a single MACIT, collagens XIII/XXIII/XXV of jawed vertebrates are paralogues that originated from the two rounds of en-bloc genome duplication occurring early in vertebrate evolution. MACITs have conserved domain architecture in which a juxta-membrane furin-cleavage site and the C-terminal 34 residues are especially highly conserved, whereas the cytoplasmic domains are weakly conserved. To study protein expression and function in a metazoan with a single MACIT gene, we focused on Caenorhabditis elegans and its col-99 gene. A col-99 cDNA was cloned and expressed as protein in mammalian CHO cells, two antibodies against COL-99 protein were generated, and a col-99-bearing fosmid gene construct col-99::egfp::flag was used to generate transgenic C. elegans lines. The encoded COL-99 polypeptide is 85 kDa in size and forms a trimeric protein. COL-99 is plasma membrane-associated and undergoes furin-dependent ectodomain cleavage and shedding. COL-99 is detected in mouth, pharynx, body wall and the tail, mostly in motor neurons and muscle systems and is enriched at neuromuscular junctions. CONCLUSIONS: Through identification of MACITs in multiple metazoan phyla we developed a model for the evolution of MACITs. The experimental data demonstrate conservation of MACIT molecular and cellular properties and tissue localisations in the invertebrate, C. elegans. PMID- 26667624 TI - RbAp48 is essential for viability of vertebrate cells and plays a role in chromosome stability. AB - RbAp46/48, histone chaperone, is a family of evolutionarily conserved WD40 repeat containing proteins, which are involved in various chromatin-metabolizing processes, but their in vivo functional relevance is yet unclear. In order to examine the biological role of pRbAp48 in chicken DT40 cells, we generated a tetracycline-inducible system for conditional RbAp48-knockout cells. Depletion of RbAp48 led to delayed S phase progression associated with slow DNA synthesis and nascent nucleosome formation, followed by accumulation in G2/M phase, finally leading to cell death. Prior to cell death, these cells exhibited aberrant mitosis such as highly condensed and abnormal chromosome alignment on the metaphase plate, leading to chromosome missegregation. Depletion of RbAp48 also caused dissociation of heterochromatin protein 1 (HP1) from pericentromeric heterochromatin. Furthermore, depletion of RbAp48 from cells led to elevated levels of acetylation and slightly decreased levels of methylation, specifically at Lys-9 residue of histone H3. These results suggest that RbAp48 plays an important role in chromosome stability for proper organization of heterochromatin structure through the regulation of epigenetic mark. PMID- 26667625 TI - How evolution of the nailing system improves results and reduces orthopedic complications: more than 2000 cases of trochanteric fractures treated with the Gamma Nail System. AB - PURPOSE: The incidence of trochanteric fractures has increased significantly during the last few decades, especially in elderly patients with osteoporosis. The dynamic/sliding hip screw and the cephalomedullary nail are the most commonly used fixation methods to treat trochanteric fractures. The improvements in the Gamma Nail System (GNS) associated with a correct surgical technique reduced the postoperative orthopedic complications. The purpose of this study was to compare the results of the different Gamma Nails. METHODS: The present study is a retrospective analysis of 2144 patients treated with GNS between January 1997 and December 2011 for trochanteric fractures, classified according to AO classification method. The patients were divided into three groups according to the nailing system: 525 were treated with Standard Gamma Nail (SGN), 422 with Trochanteric Gamma Nail (TGN) and 1197 with Gamma3 Nail. RESULTS: The overall incidence of intra-operative complications was 1.21 %; the incidence of intra operative complications for each group was 1.71 % for SGN group, 0.47 % for TGN group and 1.25 % for Gamma3 Nail group. The overall incidence of postoperative complications was 5.48 %, and the incidence for each group was 10.73 % for SGN group, 9.92 % for TGN group and 2.92 % for Gamma3 Nail group. CONCLUSION: The GNS is a safe device with a low rate of intra-operative complications. The evolution of this nail system reduces postoperative complications, thus improving the results at follow-up and confirming that the Gamma3 Nail is a safe and predictable device to fix trochanteric fracture. PMID- 26667626 TI - Primary care physicians and oncologists are partners in cancer announcement. AB - PURPOSE: The primary care physician (PCP) is central to cancer patients' management. Announcement of the diagnosis is a critical time for patients, even if they wish to be fully informed. The French National Cancer Plan, developed 10 years ago, includes a diagnosis disclosure procedure (DDP) to be used by oncologists, which makes specific provision for a time of communication with PCPs. So, we asked PCPs about their role in cancer announcement since the launching of the DDP. METHODS: A cross-sectional prospective study by postal questionnaire was sent to 500 PCPs in the largest region of France. It addressed (1) the characteristics of cancer disclosure, (2) PCPs' source of information of the diagnosis, (3) time of disclosure, (4) information exchange, and (5) the physicians' knowledge of the DDP. RESULTS: The response rate was 48 %. In 20 % of cases, oncologists delegated the announcement to PCPs. In 19 % of cases, it was the patient or their family who informed the PCP of the diagnosis. We identified three announcement phases of cancer diagnosis in the physicians' clinical practice: pre-disclosure, disclosure, and repeat disclosure. In 57 % of cases, PCPs lacked information on prognosis and in 60 % on treatment. Regarding the DDP, nearly half of PCPs did not know the procedure itself or its content. CONCLUSION: PCPs announce the cancer diagnosis, even if they have not received the necessary information to do so. The DDP needs to be adapted for use in primary care practice. PMID- 26667627 TI - Your Best Life: Coping With Emotional Pain in a Demanding Work Environment. PMID- 26667628 TI - How feedback improves children's numerical estimation. AB - Developmental change in children's number-line estimation has been thought to reveal a categorical logarithmic-to-linear shift in mental representations of number. Some have claimed that the broad and rapid change in estimation patterns that occurs with corrective feedback provides strong evidence for this shift. However, quantitative models of proportion judgment may provide a better account of children's estimation patterns while also predicting broad and rapid change following feedback. Here we test the hypothesis that local corrective feedback provides children with additional reference points, rather than catalyzing a shift to a different mental representation of number. We tested 117 children from several second-grade classrooms in a number-line feedback study. Data indicate that the proportion-judgment framework accounts for individual differences in estimation patterns, and that the effects of feedback are consistent with the unique quantitative predictions of the framework. They do not provide evidence supporting the representational shift hypothesis or, more broadly, for the proposal that cognitive change can occur rapidly at the level of entire mental representations. PMID- 26667629 TI - Ear Reconstruction-An Update. PMID- 26667630 TI - Milestones in the History of Ear Reconstruction. AB - The reconstruction of ear deformities has been challenging plastic surgeons since centuries. However, it is only in the 19th century that reports on partial and total ear reconstruction start increasing. In the quest for an aesthetically pleasing and natural-looking result, surgeons worked on the perfect framework and skin coverage. Different materials and flap techniques have evolved. Some were abandoned out of frustration, while others kept evolving over the years. In this article, we discuss the milestones in ear reconstruction-from ancient times to early attempts in Western civilization to the key chapters of ear reconstruction in the 20th century leading to the current techniques. PMID- 26667631 TI - Congenital Auricular Malformations: Description of Anomalies and Syndromes. AB - Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (~2 or 3:1), is predominantly unilateral (~70-90%), and more often involves the right ear (~60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. PMID- 26667632 TI - Surgical and Technical Modalities for Hearing Restoration in Ear Malformations. AB - Malformations of the external and middle ear often go along with an aesthetic and functional handicap. Independent of additional aesthetic procedures, a successful functional hearing restoration leads to a tremendous gain in quality of life for affected patients. The introduction of implantable hearing systems (bone conduction and middle ear devices) offers new therapeutic options in this field. We focus on functional rehabilitation of patients with malformations, either by surgical reconstruction or the use of different implantable hearing devices, depending on the disease itself and the severity of malformation as well as hearing impairment. Patients with an open ear canal and minor malformations are good candidates for surgical hearing restoration of middle ear structures with passive titanium or autologous implants. In cases with complete fibrous or bony atresia of the ear canal, the most promising functional outcome and gain in quality of life can be expected with an active middle ear implant or a bone conduction device combined with a surgical aesthetic rehabilitation in a single or multi-step procedure. Although the surgical procedure for bone conduction devices is straightforward and safe, more sophisticated operations for active middle ear implants (e.g., Vibrant Soundbridge, MED-EL, Innsbruck, Austria) provide an improved speech discrimination in noise and the ability of sound localization compared with bone conduction devices where the stimulation reaches both cochleae. PMID- 26667633 TI - The Rib Cartilage Concept in Microtia. AB - There is a long history of rib cartilage use in reconstruction for microtia. This article aims to describe the modern techniques of autologous auricular reconstruction in detail, to elucidate the modifications for certain anatomical or disease-related conditions, and to contrast the different strategies used by other surgeons. The two mainstays of successful reconstruction with excellent results are the fabrication of the framework and soft tissue management. A three dimensional framework mimics the curves, indentations, and peaks of a normal ear with maximal stability. Recently, the creation of a conchal bowl and an additional tragal strut has become a standard procedure. Soft tissue management is highly specific to each patient and equally contributes to the final result of the procedure. The correct position of the incision line and the trimming of the local flaps require thorough planning. Most of the individual modifications must be made in soft tissue management, particularly in patients with a low hairline and facial asymmetry. Autologous auricular reconstruction is a standard procedure that needs to be individualized to each patient. However, it is challenging and requires intensive training. In experienced hands, patients experience excellent results. PMID- 26667634 TI - Ear Reconstruction in Young Children. AB - The use of a porous high-density polyethylene ear implant, rather than a costal cartilage framework, allows ear reconstruction in young children before they enter school. The fact that the growth of the normal ear matures early allows for good symmetry. If the implant is covered completely with a large, well vascularized superficial parietal fascia flap and appropriately color-matched skin, an ear with excellent projection and definition can be obtained with minimal complications and long-term viability. Ear reconstruction in young children is preferred by the author because the necessary fascial flap coverage is thinner, easier to harvest than in older patients, and can be done in a single outpatient procedure with minimal discomfort or psychological trauma. PMID- 26667635 TI - Single-Stage Ear Reconstruction and Hearing Restoration Using Polyethylene Implant and Implantable Hearing Devices. AB - The use of porous polyethylene in reconstructive surgery of the auricle is becoming increasingly accepted. This is a single-stage procedure providing pleasing cosmetic rehabilitation. Further advantages are the possibility of early implantation and the lack of complications caused by harvesting costal cartilage. Additional hearing restoration using middle ear implants allows functional rehabilitation at an early stage. PMID- 26667636 TI - Porous Polyethylene Implant and Rib Cartilage in Ear Reconstruction: A Comparison. AB - Auricular reconstruction, known as the "surgical art," is one of the most difficult and complex surgeries in medicine. There are two different techniques that involve either the use of artificial material like porous polyethylene (PE) or the patient's own rib cartilage graft. The patient's indication, age, conditions requiring previous failed surgeries, and the surgeon's skill in creating the frame are the most important factors in the choice of technique. Both methods are performed in our clinic in Vienna. We experienced more complications in the early cases using PE due to surgical inexperience. The advantages of PE, such as the fact that it is a single-stage surgery, favorable aesthetic appearance (definition and projection), and the possibility of combining the reconstruction with bone conduction devices or active middle ear implants and performing in older patients, can be compared with its disadvantages, such as greater complications. Both techniques require the acquisition of considerable skill and tricks, and for this reason it is important that a skilled surgeon who has mastered these auricular reconstruction skills is available to teach the next generation. PMID- 26667637 TI - Complications after Total Porous Implant Ear Reconstruction and Their Management. AB - Microtia reconstruction using porous polyethylene implants has become an established alternative to autologous costal cartilage techniques. Few surgeons are trained in porous implant ear reconstruction (PIER), leading to a relative lack of understanding of the nuances of this type of surgery. The risks of exposure, infection, and fracture of the implant have further discouraged surgeons from performing PIERs. Meticulous technique and proper management of complications are critical to the success of surgeries involving porous implants (Medpor, Su-Por). There are a limited number of articles in the literature that report the management of complications of porous implant auricular reconstruction. The purpose of this work is to present a comprehensive review of the management of complications with PIER based on over 10 years of experience with this surgical technique. PMID- 26667638 TI - The Role of Auricular Prostheses (Epitheses) in Ear Reconstruction. AB - The artwork of making the epithesis by the dedicated anaplastologist is the prerequisite of acceptance by the patient and the key for success of this approach. However, computer science is helping with virtual planning and rapid prototyping, and it is likely to revolutionize this process in the near future. One of the advantages of the auricular prostheses is that it can be manufactured as a mirrored replica of the opposite side (if normal or near normal). Furthermore, the results are predictable, and may be shown to the patient before surgery. The developments of various implant systems allow secure retention even in unfavorable anatomic situations as in the ideally pneumatized mastoid process. The advantage of the plate systems is that they spread the loading forces to multiple smaller bone screws, rendering it thereby resistant to torque with abutment insertion or magnet change. Auricular prostheses fulfill three roles: (1) temporary measure, (2) rescue procedure in failed auricular (re)construction, and (3) definitive treatment option. Conventional retention by medical adhesives, sometimes helped by making use of the remnant, keeps its place in the use as a temporary measure or if the patient declines surgery. Today, implant-retained auricular prostheses made of silicone are state of the art for prosthetic rehabilitation of patients with auricular defects. PMID- 26667639 TI - Aesthetic Refinements in Patients with Prominent Eyes. AB - The treatment of prominent eyes is still a challenging task. As well as the surgery, proper preoperative diagnosis differentiating between patients with and without Graves ophthalmopathy plays an important role. In functionally asymptomatic patients with Graves disease suffering from the aesthetic impairment of prominent eyes, the transpalpebral decompression by intraorbital fat removal technique has been proved to be reliable, effective, safe, and easily performed by a trained and experienced oculoplastic surgeon. This technique provides long lasting results, leading to improvement not only in visual function but also in personal well-being and in the patient's social life, with a high benefit-to-risk ratio. The most powerful tool to treat the lower lid deformity and malar bags in patients without Graves disease is the subperiosteal midface lift. It shortens the lid-cheek junction and blends the retaining periorbital ligaments. Furthermore, it adds volume to the lower lid and gives a stable support. By the nature of the procedure, it also turns a negative into a positive vector. In experienced hands, Olivari's orbital decompression and Hester's midface lift are ideal options for the treatment of prominent eyes. PMID- 26667640 TI - Injury Patterns and Reconstruction in Acquired Ear Deformities. AB - Reconstruction following ear trauma presents a heterogeneous group of abnormalities with significantly more variation in presentation. The aim of the study was to analyze our experience and expound some broad principles of auricular reconstruction in acquired ear deformities. A total of 117 patients with human, animal bites and revision otoplasty presented to our clinic. Demographic data were extracted from medical records and photographs. Management options included no reconstruction, external silicone prosthesis, or autologous reconstruction. Fifty percent of patients with human bite injuries and 62% with animal bite injuries opted for autologous ear reconstruction. A flap with either a costal cartilage framework (37/39; 95%) or conchal cartilage (2/39; 5%) was used. In revision otoplasty group, 12% required autologous reconstruction either with conchal or costal cartilage. We discuss our indications, techniques, complications, and predictable pattern of injuries in human bites. Autologous auricular reconstruction of traumatic injuries is a safe procedure associated with aesthetically pleasing outcome and improved quality of life despite physical and psychosocial comorbidities. Elderly patients are more likely to opt for prosthetic camouflage. PMID- 26667642 TI - Environmental issues facing chemical, biological, radiological, and nuclear risks. PMID- 26667644 TI - Sorption of his-tagged Protein G and Protein G onto chitosan/divalent metal ion sorbent used for detection of microcystin-LR. AB - A highly sensitive, specific, simple, and rapid chemiluminescence enzyme immunoassay (CLEIA) was developed for the determination of microcystin-LR (MC-LR) by using strategies for oriented immobilization of functionally intact polyclonal antibodies on chitosan surface. Several physicochemical parameters such as metal ion adsorption, hexahistidine-tagged Protein G sorption, the dilution ratio polyclonal antibody concentration, and peroxidase-labeled MC-LR concentration were studied and optimized. The sorption in batch system of G-histidine and G proteins was studied on a novel sorbent consisting of chitosan/divalent metal ions. Transition metals as Ni++ and Zn++ were immobilized through interaction with -NH2 groups of chitosan in order to supply a material capable to efficiently remove the proteins from aqueous solutions. The maximum uptake of divalent metals onto the chitosan material was found to be 230 mg g-1 for Zn++ and 62 mg g-1 for Ni++. Experimental data were evaluated using the Langmuir and Freundlich models; the results were well fitted with the Langmuir model; chitosan/Ni++ foam was found to be the best sorbent for G-protein, maximum sorption capacity obtained was 17 mg g-1, and chitosan/Zn++ was found to be the best for G-histidine with a maximum sorption capacity of 44 mg g-1. Kinetic data was evaluated with pseudo first- and pseudo-second-order models; the sorption kinetics were in all cases better represented by a pseudo-second-order model. Under optimum conditions, the calibration curve obtained for MC-LR gave detection limits of 0.5 +/- 0.06 MUg L 1, the 50 % inhibition concentration (IC50) was 2.75 +/- 0.03 MUg L-1, and the quantitative detection range was 0.5-25 MUg L-1. The limit of detection (LOD) attained from the calibration curves and the results obtained demonstrate the potential use of CLEIA with chitosan support as a screening tool for the analysis of pollutants in environmental samples. PMID- 26667646 TI - A new approach for remediation of As-contaminated soil: ball mill-based technique. AB - In this study, a physical ball mill process instead of chemical extraction using toxic chemical agents was applied to remove arsenic (As) from contaminated soil. A statistical analysis was carried out to establish the optimal conditions for ball mill processing. As a result of the statistical analysis, approximately 70% of As was removed from the soil at the following conditions: 5 min, 1.0 cm, 10 rpm, and 5% of operating time, media size, rotational velocity, and soil loading conditions, respectively. A significant amount of As remained in the grinded fine soil after ball mill processing while more than 90% of soil has the original properties to be reused or recycled. As a result, the ball mill process could remove the metals bound strongly to the surface of soil by the surface grinding, which could be applied as a pretreatment before application of chemical extraction to reduce the load. PMID- 26667645 TI - Biochemical responses and DNA damage in earthworms (Eisenia fetida) induced by ionic liquid [omim]PF6. AB - Ionic liquids that are not that "green" to many organisms have recently been identified. This study examined the subchronic toxicity of the ionic liquid 1 octyl-3-methylimidazolium hexafluorophosphate ([omim]PF6) to earthworms (Eisenia fetida). Earthworms were exposed for a 28-day period (sampled on days 7, 14, 21, and 28) at concentrations of 0, 5, 10, 20, and 40 mg/kg. The levels of reactive oxygen species (ROS), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD)), detoxifying enzyme (glutathione S-transferase (GST)), lipid peroxidation, and DNA damage were measured. ROS significantly accumulated in all the treatment groups; the maximum ROS content was 51.9% higher than the control at 40 mg/kg [omim]PF6 on day 28. Increased SOD activities attenuated over the time of exposure, while the CAT activities of the treatment groups were similar to the controls, except on day 14. Furthermore, the activities of POD and GST were stimulated. Lipid peroxidation in earthworms was not apparent at 5 and 10 mg/kg [omim]PF6 but was quite obvious at 40 mg/kg [omim]PF6. In addition, DNA damage was dose- and time-dependent. In conclusion, [omim]PF6 caused oxidative stress and genotoxicity in earthworms. PMID- 26667647 TI - Source appointment of fine particle number and volume concentration during severe haze pollution in Beijing in January 2013. AB - Extreme haze episodes repeatedly shrouded Beijing during the winter of 2012-2013, causing major environmental and health problems. To better understand these extreme events, particle number size distribution (PNSD) and particle chemical composition (PCC) data collected in an intensive winter campaign in an urban site of Beijing were used to investigate the sources of ambient fine particles. Positive matrix factorization (PMF) analysis resolved a total of eight factors: two traffic factors, combustion factors, secondary aerosol, two accumulation mode aerosol factors, road dust, and long-range transported (LRT) dust. Traffic emissions (54%) and combustion aerosol (27%) were found to be the most important sources for particle number concentration, whereas combustion aerosol (33%) and accumulation mode aerosol (37%) dominated particle volume concentrations. Chemical compositions and sources of fine particles changed dynamically in the haze episodes. An enhanced role of secondary inorganic species was observed in the formation of haze pollution. Regional transport played an important role for high particles, contribution of which was on average up to 24-49% during the haze episodes. Secondary aerosols from urban background presented the largest contributions (45%) for the rapid increase of fine particles in the severest haze episode. In addition, the invasion of LRT dust aerosols further elevated the fine particles during the extreme haze episode. Our results showed a clear impact of regional transport on the local air pollution, suggesting the importance of regional-scale emission control measures in the local air quality management of Beijing. PMID- 26667649 TI - Physician spending and risk of malpractice claims: what about the effects of socioeconomic status? PMID- 26667648 TI - Metagenome-assembled genomes uncover a global brackish microbiome. AB - BACKGROUND: Microbes are main drivers of biogeochemical cycles in oceans and lakes. Although the genome is a foundation for understanding the metabolism, ecology and evolution of an organism, few bacterioplankton genomes have been sequenced, partly due to difficulties in cultivating them. RESULTS: We use automatic binning to reconstruct a large number of bacterioplankton genomes from a metagenomic time-series from the Baltic Sea, one of world's largest brackish water bodies. These genomes represent novel species within typical freshwater and marine clades, including clades not previously sequenced. The genomes' seasonal dynamics follow phylogenetic patterns, but with fine-grained lineage-specific variations, reflected in gene-content. Signs of streamlining are evident in most genomes, and estimated genome sizes correlate with abundance variation across filter size fractions. Comparing the genomes with globally distributed metagenomes reveals significant fragment recruitment at high sequence identity from brackish waters in North America, but little from lakes or oceans. This suggests the existence of a global brackish metacommunity whose populations diverged from freshwater and marine relatives over 100,000 years ago, long before the Baltic Sea was formed (8000 years ago). This markedly contrasts to most Baltic Sea multicellular organisms, which are locally adapted populations of freshwater or marine counterparts. CONCLUSIONS: We describe the gene content, temporal dynamics and biogeography of a large set of new bacterioplankton genomes assembled from metagenomes. We propose that brackish environments exert such strong selection that lineages adapted to them flourish globally with limited influence from surrounding aquatic communities. PMID- 26667650 TI - Impaired Health-Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia. AB - An understanding of health related quality of life (HRQoL) in children and families affected by methylmalonic acidemia (MMA) is important in planning counseling and therapeutic intervention. Liver transplantation (LT) is used as a treatment for MMA; however, its risks and benefits continue to be investigated. The purpose of this study was twofold: (1) to measure HRQoL in children and families affected by MMA using the Pediatric Quality of Life Inventory (PedsQLTM) parent version, and (2) to assess the impact of LT on HRQoL by comparing LT and non-LT patient scores and free responses. Parents/caregivers reported lower scores on the majority of the PedsQLTM scales as compared to samples of healthy children, children with solid organ transplants for indications other than MMA, and families affected by chronic conditions. Scores for children with MMA were lowest in school and social functioning and scores for families were lowest in worry and activity impairment. There were no significant differences in LT and non-LT patient scores on the PedsQLTM scales. Our results document the negative impact of MMA on HRQoL. PMID- 26667651 TI - Antimicrobial susceptibility trends among gram-positive and -negative clinical isolates collected between 2005 and 2012 in Mexico: results from the Tigecycline Evaluation and Surveillance Trial. AB - BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (T.E.S.T) is a global antimicrobial surveillance study of both gram-positive and gram-negative organisms. This report presents data on antimicrobial susceptibility among organisms collected in Mexico between 2005 and 2012 as part of T.E.S.T., and compares rates between 2005-2007 and 2008-2012. METHOD: Each center in Mexico submitted at least 200 isolates per collection year; including 65 gram-positive isolates and 135 gram-negative isolates. Minimum inhibitory concentrations (MICs) were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution methodology and antimicrobial susceptibility was established using the 2013 CLSI-approved breakpoints. For tigecycline US Food and Drug Administration (FDA) breakpoints were applied. Isolates of E. coli and K. pneumoniae with a MIC for ceftriaxone of >1 mg/L were screened for ESBL production using the phenotypic confirmatory disk test according to CLSI guidelines. RESULTS: The rates of some key resistant phenotypes changed during this study: vancomycin resistance among Enterococcus faecium decreased from 28.6 % in 2005-2007 to 19.1 % in 2008-2012, while beta-lactamase production among Haemophilus influenzae decreased from 37.6 to 18.9 %. Conversely, methicillin resistant Staphylococcus aureus increased from 38.1 to 47.9 %, meropenem resistant Acinetobacter spp. increased from 17.7 to 33.0 % and multidrug resistant Acinetobacter spp. increased from 25.6 to 49.7 %. The prevalence of other resistant pathogens was stable over the study period, including extended spectrum beta-lactamase-positive Escherichia coli (39.0 %) and Klebsiella pneumoniae (25.0 %). The activity of tigecycline was maintained across the study years with MIC90s of <=2 mg/L against Enterococcus spp., S. aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Enterobacter spp., E. coli, K. pneumoniae, Klebsiella oxytoca, Serratia marcescens, H. influenzae, and Acinetobacter spp. All gram-positive organisms were susceptible to tigecycline and susceptibility among gram-negatives ranged from 95.0 % for K. pneumoniae to 99.7 % for E. coli. CONCLUSION: Antimicrobial resistance continues to be high in Mexico. Tigecycline was active against gram-positive and gram-negative organisms, including resistant phenotypes, collected during the study. PMID- 26667652 TI - No evidence for viral sequences in five lepidic adenocarcinomas (former "BAC") by a high-throughput sequencing approach. AB - BACKGROUND: The hypothesis of an infectious etiology of the formerly named bronchiolo-alveolar carcinoma (BAC) has raised controversy. We investigated tumor lung tissues from five patients with former BAC histology using high-throughput sequencing technologies to discover potential viruses present in this type of lung cancer. Around 180 million single reads of 100 bases were generated for each BAC sample. RESULTS: None of the reads showed a significant similarity for Jaagsiekte sheep retrovirus (JSRV) and no other viruses were found except for endogenous retroviruses. CONCLUSIONS: In conclusion, we have demonstrated the absence of JSRV and other known human viruses in five samples of well characterized lepidic adenocarcinoma. PMID- 26667654 TI - Erratum to: Identification of trace levels of selenomethionine and related organic selenium species in high-ionic-strength waters. PMID- 26667653 TI - Physiological and Molecular Alterations Promoted by Schizotetranychus oryzae Mite Infestation in Rice Leaves. AB - Infestation of phytophagous mite Schizotetranychus oryzae in rice causes critical yield losses. To better understand this interaction, we employed Multidimensional Protein Identification Technology (MudPIT) approach to identify differentially expressed proteins. We detected 18 and 872 unique proteins in control and infested leaves, respectively, along with 32 proteins more abundant in control leaves. S. oryzae infestation caused decreased abundance of proteins related to photosynthesis (mostly photosystem II-related), carbon assimilation and energy production, chloroplast detoxification, defense, and fatty acid and gibberellin synthesis. On the contrary, infestation caused increased abundance of proteins involved in protein modification and degradation, gene expression at the translation level, protein partitioning to different organelles, lipid metabolism, actin cytoskeleton remodeling, and synthesis of jasmonate, amino acid, and molecular chaperones. Our results also suggest that S. oryzae infestation promotes cell-wall remodeling and interferes with ethylene biosynthesis in rice leaves. Proteomic data were positively correlated with enzymatic assays and RT-qPCR analysis. Our findings describe the protein expression patterns of infested rice leaves and suggest that the acceptor side of PSII is probably the major damaged target in the photosynthetic apparatus. These data will be useful in future biotechnological approaches aiming to induce phytophagous mite resistance in rice. PMID- 26667655 TI - Quantifying oxygen in paper-based cell cultures with luminescent thin film sensors. AB - Paper-based scaffolds are an attractive material for generating 3D tissue-like cultures because paper is readily available and does not require specialized equipment to pattern, cut, or use. By controlling the exchange of fresh culture medium with the paper-based scaffolds, we can engineer diffusion-dominated environments similar to those found in spheroids or solid tumors. Oxygen tension directly regulates cellular phenotype and invasiveness through hypoxia-inducible transcription factors and also has chemotactic properties. To date, gradients of oxygen generated in the paper-based cultures have relied on cellular response based readouts. In this work, we prepared a luminescent thin film capable of quantifying oxygen tensions in apposed cell-containing paper-based scaffolds. The oxygen sensors, which are polystyrene films containing a Pd(II) tetrakis(pentafluorophenyl)porphyrin dye, are photostable, stable in culture conditions, and not cytotoxic. They have a linear response for oxygen tensions ranging from 0 to 160 mmHg O2, and a Stern-Volmer constant (K sv) of 0.239 +/- 0.003 mmHg O2 (-1). We used these oxygen-sensing films to measure the spatial and temporal changes in oxygen tension for paper-based cultures containing a breast cancer line that was engineered to constitutively express a fluorescent protein. By acquiring images of the oxygen-sensing film and the fluorescently labeled cells, we were able to approximate the oxygen consumption rates of the cells in our cultures. PMID- 26667657 TI - Review of Dicompass DICOM Camera App for Android. PMID- 26667656 TI - lncRNAs regulate the innate immune response to viral infection. AB - Long noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as RNA regulators in various cellular processes. Increasing data reveal that they function in innate antiviral immunity through complex mechanisms. Thousands of lncRNAs are regulated by RNA virus or DNA virus infection. The significant differential expression of lncRNAs is induced by virus or host antiviral signaling mediated by interferons (IFNs) and tumor necrosis factor-alpha. In turn, these lncRNAs modulate the host immune response including the pathogen recognition receptor (PRR)-related signaling, the translocation and activation of transcription factors, the production of IFNs and cytokines, the IFN-activated JAK-STAT signaling and the transcription of antiviral IFN stimulated genes (ISGs). Using gain- or loss-of-function analysis, the effect of lncRNAs on viral replication has been investigated to elucidate the essential role of lncRNA in the host-virus interaction. lncRNAs have shown specifically elevated or decreased levels in patients with viral diseases, suggesting the possibility of clinical application as biomarkers. Here we review the current advances of viral infection-associated host lncRNAs, their functional significance in different aspects of antiviral immune response, the specific mechanisms and unsolved issues. We also summarize the regulation of lncRNAs by viruses, PRR agonists and cytokines. In addition, virus-encoded lncRNAs and their functional involvement in host-virus interaction are addressed. WIREs RNA 2016, 7:129-143. doi: 10.1002/wrna.1321 For further resources related to this article, please visit the WIREs website. PMID- 26667658 TI - Utilization of Workflow Process Maps to Analyze Gaps in Critical Event Notification at a Large, Urban Hospital. AB - Stroke care is a time-sensitive workflow involving multiple specialties acting in unison, often relying on one-way paging systems to alert care providers. The goal of this study was to map and quantitatively evaluate such a system and address communication gaps with system improvements. A workflow process map of the stroke notification system at a large, urban hospital was created via observation and interviews with hospital staff. We recorded pager communication regarding 45 patients in the emergency department (ED), neuroradiology reading room (NRR), and a clinician residence (CR), categorizing transmissions as successful or unsuccessful (dropped or unintelligible). Data analysis and consultation with information technology staff and the vendor informed a quality intervention replacing one paging antenna and adding another. Data from a 1-month post intervention period was collected. Error rates before and after were compared using a chi-squared test. Seventy-five pages regarding 45 patients were recorded pre-intervention; 88 pages regarding 86 patients were recorded post-intervention. Initial transmission error rates in the ED, NRR, and CR were 40.0, 22.7, and 12.0 %. Post-intervention, error rates were 5.1, 18.8, and 1.1 %, a statistically significant improvement in the ED (p < 0.0001) and CR (p = 0.004) but not NRR (p = 0.208). This intervention resulted in measureable improvement in pager communication to the ED and CR. While results in the NRR were not significant, this intervention bolsters the utility of workflow process maps. The workflow process map effectively defined communication failure parameters, allowing for systematic testing and intervention to improve communication in essential clinical locations. PMID- 26667659 TI - Establishing the Attention-Distractibility Trait. AB - Failures to focus attention will affect any task engagement (e.g., at work, in the classroom, when driving). At the clinical end, distractibility is a diagnostic criterion of attention-deficit/hyperactivity disorder (ADHD). In this study, we examined whether the inability to maintain attentional focus varies in the overall population in the form of an attention-distractibility trait. To test this idea, we administered an ADHD diagnostic tool to a sample of healthy participants and assessed the relationship between ADHD symptoms and task distraction. ADHD symptom summary scores were significantly positively associated with distractor interference in letter-search and name-classification tasks (as measured by reaction time), as long as the distractors were irrelevant (cartoon images) rather than relevant (i.e., compatible or incompatible with target names). Higher perceptual load during a task eliminated distraction irrespective of ADHD score. These findings suggest the existence of an attention distractibility trait that confers vulnerability to irrelevant distraction, which can be remedied by increasing the level of perceptual load during the task. PMID- 26667660 TI - Changes in Cognitive Status in COPD Patients Across Clinical Stages. AB - Chronic obstructive pulmonary disease (COPD) is a progressive disease, its prevalence increases with age. COPD is frequently associated with co-morbidities such as cognitive impairment, and their clinical relevance has risen in the recent past. Cognitive function may fluctuate with the variable components of COPD like hypoxaemia, hypercapnia, lung function, exacerbations or severity of the disease. The objectives of this study were to examine whether the cognitive status of COPD patients is different across clinical stages (exacerbation, at discharge and stable COPD) and also if there are cognitive areas that have more potential to change than others. Prospective observational clinical study: 62 patients admitted to hospital due to acute exacerbation of COPD were evaluated at hospital admission; 61 at discharge; and finally, 48 patients with stable COPD completed the study and were included in the analysis. Cognitive status was assessed with the Montreal Cognitive Assessment (MoCA). Our results show that all clinical variables improved from exacerbation to discharge COPD. MoCA total score, visuoconstructional, attention, language, abstraction, delayed recall and orientation subscores improved significantly from exacerbation to discharge COPD (p < 0.05). MoCA total score, visuoconstructional and naming subscores worsened significantly from discharge to stable COPD (p < 0.05). Finally, from exacerbation to stable COPD all the clinical variables improved; MoCA total score and naming, attention, language, abstraction and delayed recall subscores have shown significant differences (p < 0.05). Cognitive status of COPD patients is different across clinical stages, and there are cognitive areas with more potential to change than others. PMID- 26667661 TI - CO2-switchable fluorescence of a dendritic polymer and its applications. AB - The synthesis and properties of CO2 responsive and fluorescent dendritic polymers, poly(amido amine)/Pluronic F127 (PAMAM/F127), are reported in this paper. The morphologies and sizes of PAMAM/F127 dendritic polymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). PAMAM/F127 dendritic polymers showed unimolecular micelle morphologies at low concentrations, and changed to multimolecular micelles at higher concentrations. Additionally, fluorescence spectra and confocal laser scanning microscopy images showed that PAMAM/F127 dendritic polymers exhibited a fluorescent enhancement response to the presence of CO2. Apart from that, the release behavior of PAMAM/F127 gels under simulated body fluids was investigated by choosing curcumin as the hydrophobic drug. The results indicated that PAMAM/F127 dendritic polymers can be used to improve the solubility of curcumin, and the drug released faster in the presence of CO2. Such CO2 responsive fluorescent dendritic polymers are potentially applicable in cellular imaging or drug controlled release. PMID- 26667662 TI - Ovarian stimulation with human and recombinant gonadotropin - comparison of in vitro fertilization efficiency with use of time-lapse monitoring. AB - BACKGROUND: Achieving pregnancy by in vitro fertilization (IVF) treatment depends on many factors, including the ovaries' capacity and the efficiency of ovarian stimulation. The aim of this study was to assess the influence of ovarian stimulation with human and recombinant gonadotropin, as well as specific hormonal parameters, on the effectiveness of IVF and the dynamics of embryonic development. METHODS: The study involved 221 women aged 25-35 years in whom intracytoplasmic sperm injection was performed. The ovarian stimulation was carried out according to the short protocol: injections of gonadotropin-releasing hormone analogue were followed by human (hFSH) and recombinant (rFSH) follicle stimulating hormone administration. The growth of embryos was monitored with a time-lapse system. Levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH) were measured before ovarian stimulation, and levels of estradiol were assessed on the day of administration of recombinant chorionic gonadotropin. RESULTS: Pregnancy was achieved in 77 women (group A) - 42 (54.55 %) of them were stimulated with hFSH and 35 (45.45 %) were stimulated with rFSH. Among the 144 women in whom pregnancy was not achieved (group B), hFSH was administered to 73 (50.69 %) women and rFSH to 71 (49.31 %) women. In both groups subsequent embryo development stages were usually noted earlier after hFSH stimulation than after rFSH stimulation. The average values of AMH, estradiol, and estradiol per >17 mm follicle were higher in group A; in turn, FSH and LH mean levels were higher in group B. ROC curve analysis showed no statistically significant differences between accuracy of using FSH and AMH levels to predict pregnancy after IVF. CONCLUSIONS: The kind of gonadotropin applied to stimulate ovaries impacts the dynamics of embryo development - in women stimulated with hFSH, subsequent development stages were usually observed earlier than in women treated with rFSH; however, there was no statistically significant difference in pregnancy rates between women who were hFSH stimulated and those who were rFSH stimulated. The mean estradiol level was higher in women who achieved pregnancy than in women in whom pregnancy was not achieved AMH and FSH have the greater impact on achieving pregnancy than other hormones, and the value of AMH and FSH in predicting pregnancy is similar. PMID- 26667663 TI - A clinical decision support tool to screen health records for contraindications to stroke thrombolysis-a pilot study. AB - BACKGROUND: The use of intravenous thrombolysis for stroke is limited by contraindications that may be difficult to identify promptly and accurately. Evidence supports the use of information technology-based clinical decision support (CDS) tools to achieve improvements in care delivery. The objective of this pilot study was to investigate the efficacy of a CDS tool to screen health records for contraindications to intravenous stroke thrombolysis. METHODS: A CDS tool was developed to rapidly screen health information in seven affiliated hospitals for contraindications to stroke thrombolysis. A fixed-sequence, 2 period crossover study was conducted to test the efficacy of the CDS tool. Four mock patient records derived from the stroke registry that contained a total of nine contraindication items in two or more of the hospitals were used for testing purposes. The test patients were preset and balanced between groups with and without the CDS tool appearing six times in each group before recruiting the participating physicians. Physicians who were responsible for thrombolytic therapy and willing to sign informed consent were recruited. The participating physicians were asked to check a list of contraindications for two of the patients by using a shared electronic medical record system among the seven hospitals with and without the CDS tool. The test time and missed contraindications were recorded and analyzed statistically. RESULTS: A total of 14 physicians who were responsible for stroke thrombolysis were approached, and 12 signed informed consent and took the test. By using the CDS tool, the test time was reduced significantly from 14.6 +/- 7.4 to 7.3 +/- 5.2 min (P = 0.010). In a total of 54 contraindications, the number of missed contraindications was reduced significantly from 23 (42.6 %) to seven (13.0 %) (P = 0.001). The difference of missed contraindication number between the two groups was statistically significant either per physician or per contraindication item. CONCLUSIONS: By screening health records for relevant contraindications, the use of a CDS tool may reduce the time needed to review medical records and reduce the number of missed contraindications for stroke thrombolysis. PMID- 26667664 TI - Double aortic arch with right positioned descending thoracic aorta and coexistent aortic kinking. PMID- 26667665 TI - Trousseau's syndrome in a patient with gastric cancer. PMID- 26667666 TI - NGS-based Molecular diagnosis of 105 eyeGENE((r)) probands with Retinitis Pigmentosa. AB - The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE((r))) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE((r))'s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE((r)). PMID- 26667667 TI - Ligature-induced periodontitis in mice induces elevated levels of circulating interleukin-6 but shows only weak effects on adipose and liver tissues. AB - BACKGROUND AND OBJECTIVES: Our previous study demonstrated using an oral gavage model that Porphyromonas gingivalis could induce various inflammatory changes linked to periodontitis-associated systemic diseases by altering gut microbiota. A ligature-induced periodontitis model is similar to human periodontitis in various aspects: in both cases, alveolar bone resorption depends on oral bacterial load, and gingival tissue becomes infiltrated with inflammatory cells. Therefore, this model may be suitable for the analysis of bacterial burden and gingival tissue inflammation with changes related to systemic diseases. MATERIAL AND METHODS: Periodontal tissue destruction was induced by a 2 wk ligature placement around the bilateral maxillary second molar. We analyzed the expression profile of various genes in several tissues, levels of systemic inflammatory markers and induction of insulin resistance. In addition, we studied changes in gut microbiota composition and bacterial load in the oral cavity. RESULTS: Two weeks after ligature placement gingival inflammation was significantly induced with a disrupted gingival epithelial barrier and alveolar bone resorption accompanied by increased bacterial burden in the oral cavity. Gene expression analysis of the gingival tissue of ligated mice demonstrated that interleukin (Il)1b was significantly elevated and Il6 and Il17a tended to be higher in ligated mice than in untreated mice. Although serum IL-6 was significantly elevated and serum amyloid A tended to be higher in ligated compared to untreated mice, endotoxin levels did not differ between the two groups. Among the genes whose expressions are closely related to glucose and lipid metabolisms, only phosphoenolpyruvate carboxykinase 1 (Pck1) and acetyl-coenzyme A carboxylase alpha (Acaca) showed significant changes following ligature placement in the liver, with the former upregulated and the latter downregulated. However, insulin sensitivity did not change following ligature placement. Furthermore, ligature placement weakly affected the composition of gut microbiota and gene expression in the intestines. CONCLUSION: The results suggest that increased oral commensals and gingival inflammation have limited roles in the pathological changes to adipose and liver tissues, which are important organs whose dysfunctions contribute to the development of periodontitis-related systemic diseases. PMID- 26667668 TI - Crystal structure of a lipoxygenase from Cyanothece sp. may reveal novel features for substrate acquisition. AB - In eukaryotes, oxidized PUFAs, so-called oxylipins, are vital signaling molecules. The first step in their biosynthesis may be catalyzed by a lipoxygenase (LOX), which forms hydroperoxides by introducing dioxygen into PUFAs. Here we characterized CspLOX1, a phylogenetically distant LOX family member from Cyanothece sp. PCC 8801 and determined its crystal structure. In addition to the classical two domains found in plant, animal, and coral LOXs, we identified an N-terminal helical extension, reminiscent of the long alpha-helical insertion in Pseudomonas aeruginosa LOX. In liposome flotation studies, this helical extension, rather than the beta-barrel domain, was crucial for a membrane binding function. Additionally, CspLOX1 could oxygenate 1,2-diarachidonyl-sn glycero-3-phosphocholine, suggesting that the enzyme may act directly on membranes and that fatty acids bind to the active site in a tail-first orientation. This binding mode is further supported by the fact that CspLOX1 catalyzed oxygenation at the n-10 position of both linoleic and arachidonic acid, resulting in 9R- and 11R-hydroperoxides, respectively. Together these results reveal unifying structural features of LOXs and their function. While the core of the active site is important for lipoxygenation and thus highly conserved, peripheral domains functioning in membrane and substrate binding are more variable. PMID- 26667669 TI - Highly efficient preparation of sphingoid bases from glucosylceramides by chemoenzymatic method. AB - Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond beta-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield. PMID- 26667670 TI - Reversible Photomodulation of Electronic Communication in a pi-Conjugated Photoswitch-Fluorophore Molecular Dyad. AB - The extent of electronic coupling between a boron dipyrromethene (BODIPY) fluorophore and a diarylethene (DAE) photoswitch has been modulated in a covalently linked molecular dyad by irradiation with either UV or visible light. In the open isomer, both moieties can be regarded as individual chromophores, while in the closed form the lowest electronic (S0 ->S1 ) transition of the dyad is slightly shifted, enabling photomodulation of its fluorescence. Transient spectroscopy confirms that the dyad behaves dramatically different in the two switching states: while in the open isomer it resembles an undisturbed BODIPY fluorophore, in the closed isomer no fluorescence occurs and instead a red shifted DAE behavior prevails. PMID- 26667672 TI - Retene causes multifunctional transcriptomic changes in the heart of rainbow trout (Oncorhynchus mykiss) embryos. AB - Fish are particularly sensitive to aryl hydrocarbon receptor (AhR)-mediated developmental toxicity. The molecular mechanisms behind these adverse effects have remained largely unresolved in salmonids, and for AhR-agonistic polycyclic aromatic hydrocarbons (PAHs). This study explored the cardiac transcriptome of rainbow trout (Oncorhynchus mykiss) eleuteroembryos exposed to retene, an AhR agonistic PAH. The embryos were exposed to retene (nominal concentration 32 MUg/L) and control, their hearts were collected before, at and after the onset of the visible signs of developmental toxicity, and transcriptomic changes were studied by microarray analysis. Retene up- or down-regulated 122 genes. The largest Gene Ontology groups were signal transduction, transcription, apoptosis, cell growth, cytoskeleton, cell adhesion/mobility, cardiovascular development, xenobiotic metabolism, protein metabolism, lipid metabolism and transport, and amino acid metabolism. Together these findings suggest that retene affects multiple signaling cascades in the heart of rainbow trout embryos, and potentially disturbs processes related to cardiovascular development and function. PMID- 26667671 TI - Waterborne psychoactive drugs impair the initial development of Zebrafish. AB - The contamination of rivers and other natural water bodies, including underground waters, is a current reality. Human occupation and some economic activities generate a wide range of contaminated effluents that reach these water resources, including psychotropic drug residues. Here we show that fluoxetine, diazepam and risperidone affected the initial development of zebrafish. All drugs increased mortality rate and heart frequency and decreased larvae length. In addition, risperidone and fluoxetine decreased egg hatching. The overall results points to a strong potential of these drugs to cause a negative impact on zebrafish initial development and, since the larvae viability was reduced, promote adverse effects at the population level. We hypothesized that eggs and larvae absorbed the drugs that exert its effects in the central nervous system. These effects on early development may have significant environmental implications. PMID- 26667673 TI - Metabolite Damage and Metabolite Damage Control in Plants. AB - It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms. PMID- 26667674 TI - Some Important Milestones in the Field of Blood Clotting. AB - Several different kinds of 'milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen 'new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures. PMID- 26667675 TI - [Dreaming of other worlds]. PMID- 26667676 TI - [Pulmonary rehabilitation in chronic obstructive pulmonary disease (Review)]. PMID- 26667677 TI - Blessings in disguise: a review of phytochemical composition and antimicrobial activity of plants belonging to the genus Eryngium. AB - Medicinal and edible plants play a crucial role in the prevention and/or mitigation of different human diseases from ancient times to today. In folk medicine, there are different plants used for infectious disease treatment. During the past two decades, much attention has been paid to plants as novel alternative therapeutic agents for the treatment of infectious diseases due to their bioactive natural compounds such as phenol, flavonoids, tannins, etc. The genus Eryngium (Apiaceae) contains more than 250 flowering plant species, which are commonly used as edible and medicinal plants in different countries. In fact, some genus Eryngium species are used as spices and are cultivated throughout the world and others species are used for the treatment of hypertension, gastrointestinal problems, asthma, burns, fevers, diarrhea, malaria, etc. Phytochemical analysis has shown that genus Eryngium species are a rich source of flavonoids, tannins, saponins, and triterpenoids. Moreover, eryngial, one the most important and major compounds of genus Eryngium plant essential oil, possesses a significant antibacterial effect. Thus, the objective of this review is to critically review the scientific literature on the phytochemical composition and antibacterial effects of the genus Eryngium plants. In addition, we provide some information about traditional uses, cultivation, as well as phytochemistry. PMID- 26667678 TI - Antibiograms in resource limited settings: Are stratified antibiograms better? AB - Background Antibiograms often act as a reference guide for empirical selection of antibiotics. Hospital-wide antibiograms constructed on the basis of cumulative antimicrobial susceptibility data from diverse patient groups can often be misleading. In order to show the significance of age- and location-stratified antibiograms, this study compared hospital-wide antibiograms with stratified antibiograms for the clinical isolates of Pseudomonas aeruginosa. Methods Stratified antibiograms were created on the basis of patient age (<18 years, 18 50 years, >50 years) and location (inpatient or outpatient) using all 2011, 2012 and 2013 clinical isolates of P. aeruginosa isolates. Susceptibility rates were compared among cumulative and stratified antibiograms using non-parametric inferential statistics. Results The hospital-wide antibiogram under-estimated susceptibility rates in adult patients isolates (age group = 18-50 years) and over-estimated susceptibility rates in isolates from the paediatric patients and elderly. Paediatric isolates were found to be less susceptible to amikacin and imipenem, whereas isolates from elderly patients >50 years were less susceptible to ciprofloxacin. Statistically significant difference was seen in the susceptibility rates of OPD and IPD isolates of P. aeruginosa in the case of the paediatric age group. Susceptibility rates for all drugs were lower for isolates from inpatients than from outpatients. Conclusion Age and location associated differences in susceptibility rates have the potential to influence empirical antibiotic selection, which was shown in stratified antibiograms of P. aeruginosa that is obscured by hospital-wide antibiograms. PMID- 26667679 TI - [A WORKING LIFE DEDICATED TO THE JOURNAL NUTRICION HOSPITALARIA]. PMID- 26667680 TI - [THE TEN MOST CITED ARTICLES OF THE JOURNAL "NUTRICION HOSPITALARIA"]. AB - After 36 years of continued publication of the journal Nutricion Hospitalaria, a list with the ten most cited articles published in it is elaborated. The top ten most cited articles in the world literature and stratification according to language, English or Spanish, subject, or period of time published are also analyzed. Nutr Hosp is the most important Ibero latin American nutrition journal. Nutr Hosp published 369 items in 2014 gaining the fourth position among all the world's journals devoted to nutrition. Article publication in English, or simultaneously in Spanish and English and Open Access policy probably benefit the number of citations. PMID- 26667681 TI - [SOME CONSIDERATIONS ABOUT THE INTRINSIC VALUE OF THE IMPACT FACTOR OF SCIENTIFIC JOURNALS]. AB - The reason of higher number of citations of some articles is discussed. Some considerations about the journals' impact factor, its merits and its pitfalls are also made. Scientific journals' impact factor, popularized by the Institute for Scientific Information, has become an objective parameter for authors' evaluation and also for institutions and other related circumstances. There is no reason for the impact factor's gap between some English journals and those written in other languages. English journals probably benefit of the "Mathew's effect", according to which eminent scientists are more rewarded by similar contributions than others less known. It is paradoxical that most of the major achievements of our age do not appear among the 100 most cited articles. There is no homogeneity among all the articles appearing in each scientific journal: half of the articles are cited ten times more than the other half. However, those articles cited 0 times are credited like the better ones. Each article should be evaluated by its own citations, which would be its impact factor; the authors should be evaluated by their H index. PMID- 26667682 TI - [SIXTH JESUS CULEBRAS' LECTURE: GLUTAMINE AND THE CRITICAL PATIENT: THE END OF AN AGE?]. AB - In the last few years, glutamine has changed its status from a "non-essential" amino acid to "almost essential or indispensable" in the critical patient. This has occurred thanks to a series of studies and meta-analysis highlighting the beneficial effects on nosocomial infection, stay in ICU and hospital stay and mortality. After two multicentre studies (REDOXS and MetaPlus) which reviewed the effects of glutamine on critically ill patients, comments changed to: "we do strongly recommend that glutamine is not used in critically ill patients in shock or multiple organ failure" and: "there is an important questioning about the safety of this approach (combination of high- dose enteral and parenteral glutamine) which should not be ignored" and, therefore: "the committee decides to decrease the degree of recommendation for endovenous glutamine"; it currently states that glutamine "should be considered". According to another multicentre study with severe trauma patients our group (a group which in theory was much benefitted from glutamine actions), and 143 patients, did not experience any observable benefit at the usual parenteral doses. We do agree with previous studies on the prognostic value of low levels of glutamine at admittance, which was confirmed if those levels were not back to normal after its administration, although there are no readily available analytic trials for this. This divergence about the usefulness of glutamine grows up as more and more multicentre studies in critical patients show there should be a change of attitude, and probably the clinical guidelines that welcomed its use should now be amended. PMID- 26667684 TI - [ASSOCIATION OF OLFACTORY SENSITIVITY WITH ENERGY INTAKE: ROLE IN DEVELOPMENT OF OBESITY]. AB - Obesity results from an imbalance between energy consumed and energy expenditure generated. Among the factors that regulate the non-homeostatic energy intake is the olfaction, which is an important external signal that induces food intake, humans used to assess the palatability of foods and to select foods in general. MATERIALS AND METHODS: an electronic search in the databases PubMed and Scielo, where the key words used were: "smell", "energy intake" and "obesity", additionally the following limits are added to restrict the exploration, "animals", "human", "clinical trial" and "meta- analysis". RESULTS: the individual hunger state modulates olfactory sensitivity, which shows that the sensitivity of smell detection increases compared to fasting state. There are two hormones that allow us to relate olfactory sensitivity to energy intake: orexin, which increased olfactory sensitivity and energy intake and leptin that decreased olfactory sensitivity and energy intake. Obese people with BMI> 45 have low olfactory sensitivity; a situation does not change after bariatric surgery. CONCLUSIONS: to determine the association between olfactory, energy intake and obesity is fields scarcely studied and deliver new insights for the treatment of diseases where there are eating disorders involved such as obesity. In the future the conduct of clinical trials to determine causality between these two variables and molecular studies to better understand the olfactory signals relating to energy intake are necessary. PMID- 26667683 TI - [HOME AND AMBULATORY ARTIFICIAL NUTRITION (NADYA) GROUP REPORT, HOME PARENTERAL NUTRITION IN SPAIN, 2014]. AB - AIM: to communicate the results of the Spanish Home Parenteral Nutrition (HEN) registry of the NADYASENPE group for the year 2014. MATERIAL AND METHODS: data was recorded online by NADYA group collaborators that were responsible of the HPN follow-up from 1st January to 31st December 2014. RESULTS: a total of 220 patients and 229 episodes of HPN were registered from 37 hospitals that represents a rate of 4.7 patients/million habitants/year 2014. The most frequent disease in adults was other diseases (23.3%), neoplasm (20.4%) followed by radical active neoplasm (11.8%) and mesenteric ischemia (10.9%). The most frequent diagnosis for children were the congenital intestinal disorders (33.3%) followed by traumatic short bowel and other diagnosis. CONCLUSIONS: the number of participating centers and registered patients increased progressively respect to preceding years. We consider that the HPN should be regulated by the Sanitary Administration within the framework of the National Health Service Interregional Council. And its inclusion in the portfolio of health services of the different Autonomous Comunities would be beneficial for patients and professionals. PMID- 26667685 TI - KIDMED TEST; PREVALENCE OF LOW ADHERENCE TO THE MEDITERRANEAN DIET IN CHILDREN AND YOUNG; A SYSTEMATIC REVIEW. AB - INTRODUCTION: during the last decades, a quick and important modification of the dietary habits has been observed in the Mediterranean countries, especially among young people. Several authors have evaluated the pattern of adherence to the Mediterranean Diet in this group of population, by using the KIDMED test. OBJECTIVES: the purpose of this study was to evaluate the adherence to the Mediterranean Diet among children and adolescents by using the KIDMED test through a systematic review and meta-analysis. METHODS: PubMed database was accessed until January 2014. Only cross-sectional studies evaluating children and young people were included. A random effects model was considered. RESULTS: eighteen cross-sectional studies were included. The population age ranged from 2 to 25 years. The total sample included 24 067 people. The overall percentage of high adherence to the Mediterranean Diet was 10% (95% CI 0.07-0.13), while the low adhesion was 21% (IC 95% 0.14 to 0.27). In the low adherence group, further analyses were performed by defined subgroups, finding differences for the age of the population and the geographical area. CONCLUSION: the results obtained showed important differences between high and low adherence to the Mediterranean Diet levels, although successive subgroup analyzes were performed. There is a clear trend towards the abandonment of the Mediterranean lifestyle. PMID- 26667686 TI - THE EFFECT OF GARCINIA CAMBOGIA AS COADJUVANT IN THE WEIGHT LOSS PROCESS. AB - INTRODUCTION: due to the significant increase in the obesity rate in recent years, public health has been facing in many countries of the world, one of the major problems caused by this disease. Because of this, natural products arise, herbal, to assist in the treatment of obesity due to their safer effects. Among these, stands out the extract obtained from dried fruits of Garcinia Cambogia (GC), which has been studied and used as a natural supplement for weight loss. OBJECTIVE: to investigate the GC administration as a coadjuvant factor in the treatment of obesity regarding to its effectiveness, way of action, recommended daily amount, side effects and contraindications, as a way of food and nutritional security for the population. METHODOLOGY: literature review. There were consulted the database of LILACS-BIREME data, SciELO and MEDLINE and there were selected scientific articles published in English, Portuguese and Spanish, between the period of 2007 and 2014 that conducted studies involving the administration of the GC as a way of treatment for obesity. The descriptors used for research articles in the databases were the following: Garcinia Cambogia in Portuguese, and in English the terms used were "Garcinia Cambogia", "weight loss and obesity", and "Hydroxycitric Acid (HCA)"; this last one is not a descriptor indexed in Decs, but given the importance of this term for the search, it was adopted as a keyword. Thirty-four articles were identified, but only 21 were related to the objectives of this study. The first analysis of the articles was conducted by the title and then by the summary. In addition, 17 references were included because of their relevance to the study. RESULTS: in some analyzed works, there was observed that the GC showed positive effects on weight loss process, appetite reduction, body fat percentage, triglycerides, cholesterol and glucose levels, lipogenesis process, while others had no effect. CONCLUSION: studies suggest positive results about the effectiveness of the GC on the weight loss process. However, the ideal dosage has not been well established yet. There is little evidence of adverse effects and signs of protective effect against hepatotoxicity induced by ethanol. Therefore, it becomes necessary to carry out further studies to confirm the efficacy of this phytotherapy in the weight loss process. PMID- 26667687 TI - ENDURANCE TRAINING IN FASTING CONDITIONS: BIOLOGICAL ADAPTATIONS AND BODY WEIGHT MANAGEMENT. AB - INTRODUCTION: in the majority of sports the athlete is required to achieve optimal conditions both at a muscular and metabolic level as well as in body composition, increasing the lean body mass and maintaining a low body fat mass. In this context, different training protocols have been proposed in order to reduce body fat content, by maximizing fat use instead of glycogen. OBJECTIVE: to verify if the training while fasting favours the use of fatty acids due to the low glycogen levels, allowing an improvement in the performance ant the control of body weight. RESULTS: protocols have been published, differing in time periods and exercise intensity. In addition, several markers ranging from gene expression analysis to determination of circulating parameters have been assessed in order to interpret the results. Discusion: at low intensities of endurance-based exercises, adipose tissue lipolysis and muscle fat oxidation rate seem to be higher in fasting than in fed state. On the other hand, glucose metabolism is adapted in order to save glycogen stores, possibly through gluconeogenesis activation. Finally, it has been observed that protein degradation is mainly downregulated. Only one study analyses changes in body composition after fasting during long periods, thus further work is necessary to demonstrate that this is the best method to control body fat. PMID- 26667688 TI - [A GENETIC VIEW OF FAMILIAL HYPERCHOLESTEROLEMIA]. AB - OBJECTIVE: to show reviewed information of published studies relating to Familial Hypercholesterolemia (FH), nutrition, and genes involved in the development of this pathology. RESULTS: an analysis showing familial hypercholesterolemia as a disorder occuring due to mutations in gene encoding of the LDL receptor, which can be transmitted as an autosomal dominant or autosomal recessive. It's diagnosis is important for those with a greater likelihood of premature coronary disease, and can significantly reduce life expectancy. CONCLUSIONS: there are no specific clinical criteria with absolute predictive value for the diagnosis of HF, Genetic diagnosis can prove functional defects in the LDL receptor gene, constituting definitive confirmation of the diagnosis, thus the importance of presenting a genetic vision of development of this disease, which can be treated adequately through diet therapy affecting future generations in the family concerned. PMID- 26667689 TI - NUTRITIONAL SUPPORT FOR FULMINANT HEPATITIS. AB - INTRODUCTION: fulminant hepatitis (FH) is associated with exacerbated hypercatabolism, hypoglycemia and hyperammonemia that are accompanied by the release of proinflammatory cytokines and catabolic hormones into the systemic circulation worsening patient's clinical condition. Nutritional support is a crucial element for the recovery of these patients. OBJECTIVES: the aim of this review is to update Nutritional Support for Fulminant Hepatitis. METHODS: the review was performed using electronic search on Medline-PubMed using Mesh-terms. RESULTS AND DISCUSSION: there are not many data available on nutritional support to fulminant hepatitis or acute liver failure. Strategies for initial nutritional intervention are focused on the control of the previously described FH metabolic derangements, and should be individualized according to the severity of patient's clinical condition. Energy and protein can be provided in amounts of 25-40 kcal/kg/day and 0.8-1.2 g/kg/day, respectively. Enteral nutrition therapy is indicated for patients with advancing encephalopathy or for those who cannot be properly fed orally. Euglycemia must be achieved and protein intake can be based on BCAA formulae. Lipids can be administered as energy supplementation with caution. Adequate nutrition therapy can potentially reduce morbidity and mortality of FH patients. PMID- 26667690 TI - [THE ROLE OF MATERNAL DIET IN METABOLIC AND BEHAVIOURAL PROGRAMMING: REVIEW OF BIOLOGIC MECHANISMS INVOLVED]. AB - Over the last few years, a considerable amount of studies have focused on the effect of undernutrition and overnutrition during critical periods of offspring development and their risk of developing metabolic diseases later in life. Additionally, inadequate maternal diets have been involved in the malprogramming of brain functions and some behaviours. Several mechanisms have been associated with the process of malprogramming such as epigenetics modifications, excessive oxidative stress or hypothalamic alterations. This evidence supports the idea that nutritional prevention strategies must be considered for offspring during early development stages that include the preconceptional period. Additionally, studying involved mechanisms could be particularly useful in the search of efficient therapies against malprogramming. PMID- 26667691 TI - [NUTRIENTS AND RADIOTHERAPY; REVIEW OF THE LITERATURE]. AB - INTRODUCTION: nutrition is an important influence on treatments and quality of life of cancer patients. The relationship between different nutritional components and radiotherapy is today a topic of growing interest. OBJECTIVE: to evaluate the influence of macro and micronutrients on tolerance and effectiveness of radiotherapy and their role in modulating chronic toxicity. MATERIALS AND METHODS: we performed a research of the published literature by consulting the MEDLINE database and Cochrane Library online between 1995 and 2015, relevant publications based on impact factor were selected. Data from the analyzed studies were exposed in sections by type of nutrient. RESULTS: most of the studies showed common features: small sample sizes, high heterogeneity, underpowered results and few prospective randomized studies. In the section of fiber, its use in prophylaxis and treatment of radiation enteritis has been successfully evaluated in some studies, although evidence of its recommendation is still weak. Omega 3 and omega 6 fatty acids have a high metabolic potential, however the evidence regarding this benefit is limited to observational studies in certain tumors. Among the amino acids, glutamine is the most studied, and controversial results of its effect on mucositis, esophagitis and radiation enteritis were found. Vitamins and minerals are a heterogeneous group of substances that showed potential benefit due to their antioxidant activity and their supposed protector effect against toxicity secondary to radiotherapy. Ketogenic diets are beginning to be clinically studied after promising preclinical results. CONCLUSIONS: the analyzed studies show controversial or inconclusive results regarding the influence of nutrients in the radiotherapy. It has been not found Sorong evidence about their role in patients receiving ionizing radiation. Well-designed, prospective and randomized studies are needed to establish recommendations. PMID- 26667692 TI - [HIGH-INTENSITY INTERVAL EXERCISE THERAPY TO REDUCE CARDIOVASCULAR RISK FACTORS IN PEOPLE WITH THE METABOLIC SYNDROME; SYSTEMATIC REVIEW WITH META-ANALYSIS]. AB - Metabolic syndrome is a cluster of cardiovascular risk factors including central obesity, high blood pressure, insulin resistance and dyslipidemia. To determine the effect of high intensity interval exercise on cardiovascular risk factors in people with metabolic syndrome. METHODS: we searched the basis of WOS, Medline, Lilacs, PEDro data and the Epistemonikos and metasearch Trip Database. A manual search was conducted, monitoring relevant references are made, protocols of RCTs were searched and contacted experts in the area. RESULTS: the pre-remove search yielded a total of 239 potentially eligible articles, according to the eligibility criteria only include three systematic reviews. CONCLUSION: there are no major differences in relation to body mass index, waist circumference, fasting glucose, high density lipoprotein and triglycerides. Regarding blood pressure was higher than continuous moderate-intensity exercise. Comparing the high-intensity interval exercise versus control, the first was superior in all analyzed results. PMID- 26667693 TI - [EFFICACY OF SELF-MONITORING IN WEIGHT LOSS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED STUDIES]. AB - INTRODUCTION: different studies have shown a strong relationship between self monitoring and weight loss. The objective of this review was to analyze randomized clinical trials using self-monitoring as a strategy for weight loss. METHODS: a search was conducted in PubMed database of randomized controlled trials using self-monitoring for weight loss in adults, published in English and Spanish, from January 1st, 2009 to April 30th, 2015. The sample size, age, weight loss, BMI, intervention strategy, duration, and retention rate, were recorded. RESULTS: six studies met the selection criteria. The intervention and the follow up ranged from 3 to 12 months. The study population ranged from 18-74 years of age and included subjects from 50-329. Weight loss ranged from 1.14 to 2.1 kg in the control group and -1.27 to -6.1 kg in the intervention group. The six studies determined a greater weight loss in the self-monitoring group with moderate to high evaluation evidence. CONCLUSION: greater weight loss was consistently found in the self-monitoring group. These results suggest the need to use self monitoring as a strategy for weight loss. PMID- 26667694 TI - [ASSESSMENT OF THE GENETIC MODIFICATION INDUCING DIET THROUGH BLOOD MONONUCLEAR CELLS]. AB - The term nutrigenomics was created to describe how nutrition affects genes and the functions of the protein, at the transcriptional level, proteomic, and metabolic. Using changes in gene expression in blood mononuclear cells could be a model to assess the dietary intervention studies in order to understand the underlying mechanisms and impact of diet and nutrients in atherosclerosis, resistance insulin, obesity and diabetes mellitus. There are studies that have changed the dietary intake of cholesterol, polyunsaturated fat, monounsaturated, antioxidants and decreased caloric intake showing a variety of effects on the expression of mRNA in blood mononuclear cells related to inflammation, immunity, lipid metabolism genes, etc. These molecular findings entrench awareness of our body's response to diet and open up the possibility of rapid analysis of new diagnostic pathways in this area of knowledge and even new therapeutic tools. PMID- 26667696 TI - [NON PHARMACOLOGICAL METHODS TO REDUCE PAIN IN NEWBORNS; SYSTEMATIC REVIEW]. AB - BACKGROUND: newborns require diagnostic and preventive procedures since the early days of life, such as the heel prick screening for metabolic disorders, intramuscular injection of vaccines and, in some cases, channeling venous route. Which are often associated with a painful sensation. The evaluation of the intensity of painful stimuli in newborns has been studied in recent years. Various scales that collect physiological and behavioral parameters have been used. This somewhat has allowed us to get closer to the intensity of pain perceived by the child, and to decide if analgesia is necessary. In regards of methods of pain relief, the most important ones are the nonpharmacological approaches due to their safety, effectiveness and low cost. Therefore, we analyze the studies that evaluate the effectiveness of nonpharmacological interventions for painful procedures (IFN) in reducing pain in neonates. METHODS: a systematic search would be performed and 21 specific articles on the subject would be selected, following the PRISMA guidelines. RESULTS: numerous studies have proven the effectiveness of nonpharmacological interventions in relieving pain in term and preterm infants. It highlights a methodological choice, especially in the measuring of painful stimulus. It requires greater involvement on the part of health workers due to the negative consequences that entails the feeling of pain at an early age, including sleep disturbances. CONCLUSIONS: we conclude that some of the nonpharmacological interventions are most commonly used oral administration of sweet solutions, breastfeeding and kangaroo, which have proven effective, as it involves numerous benefits for the baby. However, further studies are required in this regard, and the implementation of a universal evaluation method for the subsequent evaluation of results in the medium and long term. PMID- 26667695 TI - [MATERNAL DIABETES MELLITUS AND ITS IMPACT ON CHILD NEURODEVELOPMENT; SYSTEMATIC REVIEW]. AB - BACKGROUND: at present, diabetes has become a global health problem. The consequences that entails, both short and long term, do more studies and knowledge necessary for detection, control and treatment. Moreover, its prevalence is increasing in both the general population and pregnant women. Numerous effects and complications have been reported in infants of diabetic mothers, such as fetal macrosomia, hypoglycemia and increased risk of developing obesity. This condition could have negative effects on the neurological development of the child and could affect his intellectual capacity and increase cognitive impairment. AIMS: to analyze the studies which have investigated in the relationship between diabetes mellitus during pregnancy and its impact on child neurodevelopment short and long-term. METHODS: we performed a systematic search and 20 specific articles on the subject selected would be selected following the PRISMA guidelines. RESULTS: in the studies consulted include a large methodological variety in both instruments and cognitive assessment scales, as in the age at which the sample is studied. However, most researchers conclude that maternal diabetes can have consequences for the child, both short and long-term. A higher rate of obesity, impaired glucose tolerance, cardiovascular and metabolic disorders and neurodevelopmental impairment is also described, which increase the neurobehavioral disorders and intellectual disability. CONCLUSIONS: most of the studies are agree in describing neurodevelopmental disorders in children of diabetic mothers, both in cognition and in the specific areas related to expressive language, social relations, graphical skills and psychomotor development. Other research has linked maternal diabetes with an increased incidence of autism spectrum disorders such as hyperactivity, attention deficits and schizophrenia. PMID- 26667697 TI - [REBOUND EFFECT OF INTERVENTION PROGRAMS TO REDUCE OVERWEIGHT AND OBESITY IN CHILDREN AND ADOLESCENTS; SYSTEMATIC REVIEW]. AB - BACKGROUND: studies show that overweight and obesity are the result of a complex interaction between genetic and environmental factors that begins prenatally. In evidence of this relationship the potential impact of prenatal nutrition experience in the development of the endocrine and neuroendocrine systems that regulate energy balance, with special emphasis on leptin, an adipocytederived hormone. Different authors relate the risk of obesity with rapid weight gain in the first years of life. Breastfeeding children have a lower degree of abdominal adiposity and, therefore, lower waist circumference. Similarly, it has been associated with exclusively breastfeeding with a slower weight gain rate of about 20 %. In the study of obesity, a rebound effect is considered when the child recovers its initial weight a year after finishing the procedure. This problem is common, therefore family intervention is essential in order to achieve the child's motivation to lead a healthy life. For this review we have selected studies to evaluate interventions of medium and long term in childhood obesity, ensuring adherence to treatment and the rebound effect, once the intervention ended. AIM: to review studies examining the rebound effect and adherence to weight loss treatments for children and adolescents with overweight and obesity. METHOD: the systematic review was prepared following the PRISMA guidelines. Are selected 19 studies related to the proposed issue. RESULTS: several authors have established the beneficial short and long term effects of interventions that combine diet and physical activity among obese children. These results show the importance of multidisciplinary treatment programs for childhood obesity, emphasizing its encouraging longterm effects. CONCLUSIONS: there are studies were the rebound effect in short duration programs is evident. During interventions it is significantly reduced BMI, but then increased quickly to reach even higher levels initial weight. The most effective type of actions tend to be those including the family and schools, they are multidisciplinary and they have a duration longer than 1 year. PMID- 26667698 TI - MEDITERRANEAN DIET IS ASSOCIATED WITH LIVER HISTOLOGY IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE. AB - BACKGROUND: clinical data on impact of the Mediterranean diet on the the stage of non alcoholic fatty liver disease are limited and these studies have heterogeneous designs. AIM: we decide to explore any potential associations between adherence to the Mediterranean diet and histological characteristics of patients with NAFLD. METHODS: a sample of 82 patients was analyzed in a cross sectional study. To evaluate the level of adherence to the Mediterranean dietary pattern the 14-Item Mediterranean Diet Assessment Tool was used. RESULTS: thirty five patients (42.7%) had a low grade of steatosis (grade 1 of classification) and 47 patients (57.3%) had a high grade of steatosis (grade 2 and 3). Fifty-six patients (68.3%) had liver steatohepatitis and forty-two patients (51.2%) had liver fibrosis. In the logistic regresion analysis, one unit of the 14-Item Mediterranean Diet Assessment Tool was associated with a lower likehood of having steatohepatitis odds ratio 0.43 (CI:95%: 0.29-0.64) and steatosis 0.42 (CI:95%: 0.26- 0.70). Secondly, one unit of HOMA-IR was associated with higher likehood of having steatosis odds ratio 2.01 (CI:95%: 1.08-3.71) and liver fibrosis 1.38 (CI:95%: 1.10-1.80) . CONCLUSIONS: greater adherence to the Mediterranean diet was associated with lower likelihood of high grade of steatosis and presence of steatohepatitis. PMID- 26667700 TI - ANTHROPOMETRY TO IDENTIFY HIGH VISCERAL FAT AREA IN POSTMENOPAUSAL WOMEN. AB - INTRODUCTION: the evaluation of the body fat distribution by anthropometry can serve to identify excess visceral fat. This diagnosis will enable implementation of specific measures to both prevent and treat excess visceral fat in postmenopausal women. OBJECTIVE: the aim of this study was to analyze different anthropometric indicators and identify the best cutoff points to discriminate subjects with high visceral fat area (HVFA) in postmenopausal women. METHODS: cross-sectional study with a sample of 255 postmenopausal women. Different Receiver Operating Characteristic (ROC) curves were constructed and the areas under them compared in terms of the conicity index (C-index), body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), weight-to-height ratio (WHtR) and HVFA. Sensitivity and specificity identified the best cutoff points between the different anthropometric indicators in order to discriminate subjects with HVFA. The confidence interval was set at 95%. RESULTS: statistically significant areas under the ROC curve were found for all anthropometric indicators analyzed. The following cutoff points, with their respective sensitivities and specificities to discriminate subjects with HVFA, were suggested: C-index (1.19; 75.00%- 74.77%); BMI (27.3 kg/m2; 81.08%-80.37%); WHR (0.98; 90.54%-83.18%); WC (85 cm; 85.14%-81.31%); and WHtR (0.55; 80.41%-80.37%). CONCLUSION: these results demonstrate that anthropometric indicators identify HVFA well in postmenopausal women and can be used instead of more sophisticated exams to detect high levels of visceral fat. PMID- 26667699 TI - BODY COMPOSITION CHANGES DURING A MULTIDISCIPLINARY TREATMENT PROGRAMME IN OVERWEIGHT ADOLESCENTS: EVASYON STUDY. AB - INTRODUCTION: the main objectives of weight-loss interventions are to decrease fat mass while maintaining fatfree mass. OBJECTIVE: our aim was to address effectiveness body composition changes in overweight adolescents assessed by different body composition methods following an obesity intervention programme. MATERIAL AND METHODS: the life-style intervention was multi-disciplinary, with 13 months follow-up. Participants were 13-to-16 year-old overweight, or obese, Spanish adolescents. The adolescents (n = 156; 54.8% females) had body composition measured with anthropometry, dual-energy X-ray absorptiometry and air displacement plethysmography. All measurements were made at baseline, and after 2 and 13-months. Repeated measures analysis of covariance to compare mean anthropometric changes over time and the Bonferroni correction were applied. Imputation of anthropometric measures was performed. RESULTS: a high significant decrease in fat mass index was achieved in males after 2-and 13-months of intervention as measured by anthropometry (1.16 and 1.56 kg / m2, respectively), X-ray absorptiometry (1.51 and 1.91 kg / m2) and plethysmography (2.13 and 2.44 kg/m2). Moreover, a short and long-term maintenance of fat-and fat-free mass index was observed by X-ray absorptiometry in females (0.94 and 0.68 kg/m2). CONCLUSION: our multidisciplinary approach to lifestyle intervention has a favourable impact on body fat mass and fat-free mass index as well as waist-to height ratio, over 13 months intervention in overweight and obese adolescents. PMID- 26667701 TI - ANTHROPOMETRIC INDICATORS OF GENERAL AND CENTRAL OBESITY IN THE PREDICTION OF ASTHMA IN ADOLESCENTS; CENTRAL OBESITY IN ASTHMA. AB - OBJECTIVE: to determine the prevalence of asthma risk associated with anthropometric indicators of excess weight and body fat distribution. METHODOLOGY: cross-sectional study including adolescents between 10 and 19 years of age. The anthropometric indicator used to classify excess weight was the body mass index (BMI-Z); those used for abdominal adiposity were waist circumference (WC), waist-to-height ratio (WHtR) and the conicity index (CI). Asthma characteristics were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The significance level was 5%, and the analyses were performed using Statistical Package for the Social Sciences (SPSS) Version 18.0. RESULTS: adolescent students (n = 1362; 788 [57.9%] female) with a mean age of 15.65 +/- 1.24 years were evaluated. A high prevalence of asthma, excess weight (BMI-Z) and excess abdominal adiposity (WC and WHtR) was observed in the females. Only CI values for excess abdominal adiposity were higher for males than for females. Adolescents with excess abdominal adiposity, as shown by the WHtR, had a 1.24 times higher risk of having asthma compared with non-obese adolescents. Boys with excess abdominal adiposity, as classified by CI, presented a 1.8 times greater risk of asthma. The risk of severe asthma was 3 times higher among adolescents who were classified as severely obese via the BMI Z. CONCLUSION: this study showed that excess body weight and abdominal obesity are associated with an increased risk of asthma and asthma severity in adolescents. Thus, additional BMI measurements are suggested for asthmatics. PMID- 26667702 TI - [ANTHROPOMETRIC INDICES AND ITS RELATIONSHIP WITH BIOCHEMICAL MARKERS IN WOMEN]. AB - OBJECTIVE: to analyze the relationship between anthropometric indices of adiposity and some blood markers of risk for development of metabolic disease in healthy women with different body weight. METHOD: participated 23 women of 21.0 +/- 2.9 years old. Their body mass index (BMI), waist hip ratio (WHR) and proportional sum of six skinfolds (SP6P) were obtained by anthropometry. Blood glucose and triglycerides were determined by colorimetric enzymatic technique and insulin by enzymatic immune assay. Descriptive statistics and multiple linear regression (backward) were performed. RESULTS: BMI alone proved to be a predictive factor for blood glucose (p=0.000) and triglycerides concentrations (p = 0.000), while ICC could be a better predictor of insulin (p=0.000). CONCLUSIONS: excess of body weight seems to explain the increased concentrations of glucose and triglycerides while the raised central adiposity may influence insulin levels. PMID- 26667703 TI - [TRENDS TO INCREASED BODY FAT AND BLOOD PRESSURE OF UNIVERSITY STUDENTS IN TWO COHORTS (2009-2014)]. AB - OBJECTIVE: a) describe changes in body adiposity, b) quantify the increase in blood pressure and c) verify if blood pressure increases according to the categories of body fatness in two cohorts (2009-2014) in university students. METHODS: two transverse measurements made in 2009 and 2014. The 2009 sample consisted of 309 university students (138 men and 171 women) and 2014 by 319 young people (136 men and 183 women) were compared. Weight, height, body mass index, waist circumference and systolic and diastolic blood pressure were evaluated. RESULTS: males were significantly increased body adiposity (BMI = 1.9 kg/m2 and CC = 6.4 cm), (p < 0.001), while women increased blood pressure (DBP = 5.7 mmHg and SBP = 6.6 mmHg) as a function of body fat in a range of 5 years (p < 0.001). CONCLUSION: males increased their body fat, while women increased blood pressure. The results suggest the adoption of healthy lifestyles to combat excess weight and the presence of hypertension in young students. PMID- 26667704 TI - INFLUENCE OF SOCIO-ECONOMIC AND DEMOGRAPHIC FACTORS, FEEDING AND PHYSICAL ACTIVITY ON NUTRITIONAL STATUS OF 8-15-YEAR-OLD BULGARIAN CHILDREN AND ADOLESCENTS: PRELIMINARY RESULTS. AB - OBJECTIVE: to study of impact of some socio-economic and demographic factors, feeding and physical activity on the prevalence of overweight, obesity and underweight among Bulgarian children and adolescents. MATERIAL AND METHODS: the sample of this research included 881 children and adolescents from both sexes, aged from 8 to 15 years, that were measured transversally in the period 2012- 2014 in eight government school in Smolyan region, Bulgaria. Of each child the height and weight were measured and body mass index (BMI) were calculated. The evaluation of nutritional status was made using the IOTF cut-off points of BMI for children and adolescents. By the questionnaire the information about educational level of parents, number of children in the family, place of residence, nutrition and feeding habits and physical activity of children and adolescents were collected. The data were analyzed by software Statistica 10.0. RESULTS: there is a significant positive relation between the factor ''overeating" and the BMI values for both sexes and a negative relation between the factor ''meals frequency" and BMI for boys (p. PMID- 26667705 TI - [EFFECTIVENESS OF COMPREHENSIVE TREATMENT ON THE PREOPERATIVE CONDITIONS OF OBESE WOMEN CANDIDATES FOR BARIATRIC SURGERY]. AB - INTRODUCTION: in Chile, a high prevalence of women presents morbid obesity, this condition generates serious medical complications and high costs for public health. OBJECTIVE: to determine the effects of a total treatment program consisting of physical exercise, psychological therapy and nutrition education on the preoperative conditions of obese women candidates for bariatric surgery. MATERIAL AND METHODS: nineteen women between the ages of 30 and 55 applicants to bariatric surgery, with morbid obesity (n=6) or obesity and comorbidities (n=13), underwent a program of comprehensive treatment of sixteen weeks duration (3 session/week). Before and 72 hours after the last intervention session was evaluated on fasting (>=12 hours): body weight, body mass index (BMI), percentage of body fat (% BF), contour waist (CW) and basal blood glucose. Cardiorespiratory fitness was also estimated. RESULTS: the average age was 40.32 years, post sixteen weeks of comprehensive treatment study variables improved significantly (p. PMID- 26667706 TI - [MALNUTRITION BY EXCESS IN CHILDREN-ADOLESCENT AND ITS IMPACT ON THE DEVELOPMENT OF RISK CARDIOMETABOLIC AND LOW LEVELS OF PHYSICAL PERFORMANCE]. AB - BACKGROUND: in Chile, the increase of childhood obesity has become a pandemic, and it has become a major public health problem. OBJECTIVE: the purpose of this study was to determine the prevalence of malnutrition in children-adolescents and to analyze its association with cardiometabolic risk and physical performance. MATERIAL AND METHODS: 342 students participated in this investigation (191 men and 151 women), who were between 11 and 16 years old, was evaluated index of corporal mass (IMC), body mass percentage (BMP), waist contour (WC), waist-to height ratio (WHtR) and physical yield across multiple test. RESULTS: the 3.2 % of the children-adolescent had low weight, the 48.5 % normal weight, 30.9 % overweight and 17.3 % were obese. The categories were analyzed as the presence or not of overweight and obesity. It was reported an inverse relationship between nutritional status and physical performance. School children with obesity, in comparison with those without, showed a significant increase in anthropometric measures, as well as a decrease in the physical performance (p. PMID- 26667707 TI - THAO-CHILD HEALTH PROGRAMME: COMMUNITY BASED INTERVENTION FOR HEALTHY LIFESTYLES PROMOTION TO CHILDREN AND FAMILIES: RESULTS OF A COHORT STUDY. AB - INTRODUCTION: childhood obesity is one of the main public health concerns. The multifactorial and multilevel causes require complex interventions such the community based interventions (CBI). Thao-Child Health Programme is a CBI implemented in Spain since 2007. GOAL: show the Thao methodology and the latest cross-sectional and longitudinal results. METHODS: longitudinal cohort study (4 years of follow- up) and cross sectional study. RESULTS: the longitudinal study found an increase of 1% in the overweight prevalence after a follow-up of 4 years of Thao-Programme implementation in 10 municipalities with 6 697 children involved. The cross-sectional study carried out with 20 636 children from 22 municipalities found a childhood overweight prevalence of 26.6%. DISCUSSION: currently a brake in the increase of childhood overweight prevalence is considered a success due to the high prevalence worldwide. More studies well methodologically performed are needed to know the efficacy of the CBI's in this field. PMID- 26667708 TI - [OVERWEIGHT AND OBESITY IN CHILDREN AND ADOLESCENTS IN FULL TIME SCHOOLS MORELOS, MEXICO]. AB - INTRODUCTION: in Mexico, although there are low intakes of some nutrients; there are higher total energy, fat and sodium and common inadequate physical activity in schools, which originates the presence of overweight and obesity. Objetive: the aim of this study was to identify the prevalence of overweight and obesity in school children full- time state of Morelos (Mexico). SUBJECTS AND METHODS: a cross sectional study in 30 966 students 3-15 years attending 186 schools. The nutritional status was obtained through the Body Mass Index, considering the age and sex; weight was measured with SECA 813 scales and height with stadiometer SECA 213; international benchmarks were used. RESULTS: 36 482 boys and girls censused, it's measured at 30 966 (84.9%) attended the day of visit. The overall prevalence of underweight was close to 8%, and the combined prevalence of overweight and obesity exceeded 25%. Were higher prevalences of underweight and obesity in men. CONCLUSIONS: one in 12 children are underweight; one in four, overweight and one in nine obese. The male population is more vulnerable to suffer consequences for nutritional deficiencies and excesses. Specific studies are needed to differentiate and address obesity primary type and associated risks to define future actions. PMID- 26667709 TI - THE INFLUENCE OF HLA-DQ2 HETERODIMERS ON THE CLINICAL FEATURES AND LABORATORY OF PATIENTS WITH CELIAC DISEASE. AB - BACKGROUND AND AIM: the essential genetic marker related with celiac disease (CD) is the HLA-DQ2 molecule encoded by the DQA1*0501 and DQB1*0201 genes. The aim of this study is to evaluate effect of these alleles on the clinical, serological and histological features of Turkish children with celiac disease. MATERIAL AND METHODS: we divided 36 celiac patients to 4 groups according to their HLA-DQ2 genotype based on the presence or absence of DQA1*0501 and DQB1*0201 alleles. Group 1: 4 patients had no HLA-DQ2A1*0501 and DQ2B1*0201 alleles, Group 2: 12 patients had at least one of these alleles with heterozygous status, Group 3: 12 patients had both alleles with heterozygous status, Group 4: 8 patients had both alleles with homozygous status. We compared groups according to the clinical, serological, histological, and biochemical features. RESULTS: there was no statistical significance among the groups for age, body mass index (BMI), weight for height, and onset of symptoms. However, both in groups 3 and 4 compared with groups 1 and 2, minor differences were observed for BMI and anti-gliadin antibody (AGA) without statistical significance. According to the anti-endomysial antibody (EMA), Marsh scores, clinical presentations, hematological and biochemical values, there was no statistical significance among groups without constipation that observed higher rate in the 4th group without statistically significance. Hypothyroidism was detected in one patient (25%) in the lowest genetic load group (Group 1) with statistically significance (p < 0.046). CONCLUSION: in this study, small differences found among groups were not elucidated the impact of HLADQ2 A1*0501 and DQ2B1*0201 alleles on the clinical, serological and laboratory manifestations of celiac patients. Further studies are needed to assess the effect of reported HLA alleles and other genetic polymorphisms on CD outcomes in children. PMID- 26667710 TI - [BREAST FEEDING AS PREVENTIVE FACTOR FOR OSTEOPOROSIS IN ADULT WOMEN]. AB - INTRODUCTION: breastfeeding is considered protective of osteoporosis, by endocrine changes, such as the rise of intestinal absorption of calcium and the renal conservation of the same, however, other studies demonstrate that with more one child they present a loss of bone mineral density (BMD) (2-9%). OBJECTIVE: to determine if breastfeeding is a protective factor or a risk in osteoporosis in Queretaro's women. SUBJECTS AND METHODS: retrospective study of cases y controls. 114 women from 35 to 60 years divided in control group (without breastfeeding) and women those that breastfeed. Diagnostic of BMD by bone densitometry of two regions: Hip (femur) and lumbar. Clinical history applies. Criteria of inclusion: age 35-60 years. Criteria of exclusion: consumption: calcium, hormonal replacement therapy, treatment for osteoporosis: breastfeeding or pregnant. It will provide evidence of a central trend, T couplet, correlations, Chi2 y profitable reasons. RESULTS: breastfeeding was found to have a protection factor con 0.903 OR (0.768-1.006). Inverse correlation of BMI/BMD in hip and lumbar regions, in women that did not breast contrary to those that did breastfeed. In both groups in was determined a greater age of pregnancy with greater BMD in the hips and greater size of the child, only in women that breastfeed. Being the obesity factor of the women that breastfeed. However, a inverse correlation was found among Age/BMD in three regions from women that breasted, contrary to those that did not breastfeed specifically in the BMD lumbar. CONCLUSION: breastfeeding is beneficial for the mother as it is a protective factor against osteoporosis, as long as it holds the first 6 months and for newborn optimal linear growth. PMID- 26667711 TI - OBJECTIVELY MEASURED PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOUR PATTERNS IN CHILEAN PRE-SCHOOL CHILDREN. AB - INTRODUCTION: the negative effects of physical inactivity and sedentary behaviour (SB) on children's health have been widely supported by evidence. However, evidence on how these behaviours are manifested in pre-school children is limited. The study aim was to evaluate objectively measured physical activity (PA) and SB patterns in Chilean pre-school children. METHODS: twenty-five children (4.8 ?} 0.50 years, 48% male) completed ambulatory monitoring with an ActivPALTM micro accelerometer and inclinometer. Time spent while walking, standing and sitting/lying, as well as daily steps were measured and compared by day of the week (weekday/weekend) and time of day. RESULTS: mean walking time was 147.2 ?} 52.23 minutes/ day. Mean time spent in SB was 468.3 ?} 92.22 min/day, with statistical differences between week and weekend days (484.8 minutes/day vs. 426.8 minutes/day, p = 0.03). 50% of total steps were accrued in accumulations of less than 100 steps/minute, while 50% of time spent in SB was accumulated in bouts of 35 seconds or less. DISCUSSION: pre-school children have intermittent PA and SB patterns. On weekdays children spent sitting longer than at weekends, therefore an opportunity exists for changing this behaviour during class time. This report on PA and SB patterns presents valuable information for designing and implementing strategies to enhance PA levels and decrease time spent in SB among pre-school children. PMID- 26667712 TI - [COMPARISON OF FREE CARNITINE LEVELS WITH NUTRITIONAL STATUS IN INFANTILE NEPHROPATHYC CISTINOSIS PATIENTS]. AB - INTRODUCTION: infantile nephropathic cystinosis (INC) is an autosomal recessive disorder that causes defects in cystine transport with subsequent accumulation in almost all body tissues, especially kidneys. There are few studies regarding the nutritional status assessment of patients with INC. It has been reported that patients with INC showed increased urinary losses of carnitine, resulting in plasma and muscle carnitine deficiency also increased metabolic requirements of carnitine in this patients have also been proposed, but to date carnitine supplementation is controversial. OBJECTIVE: the aim of this study was to compare carnitine blood concentrations with nutritional status assessed by three anthropometric parameters: body mass index, mid-upper arm circumference and tricipital skin fold in patients with INC. MATERIAL AND METHODS: anthropometric assessment of 10 patients with INC which included measurement of weight, height, mid-upper arm circumference and tricipital skin fold thickness. Free carnitine (C0) was measured by tandem mass spectrometry in fasting blood samples. RESULTS: a total of 10 patients with INC were analyzed, 5 with and 5 without renal graft. According to the body mass index, 3/10 presented malnutrition. Muscular mass was found low in 8/10 patients (3 without renal graft and all the transplanted) the mid-upper arm circumference showed correlation with C0 blood concentrations (r2 = 0.353); non transplanted patients had C0 levels significantly lower than the transplanted ones (Chi2 = 0.0027). CONCLUSION: in this study we found that 70% of patients had low C0 blood levels that had a correlation with depleted lean body mass. It is recommendable to evaluate the nutritional status of these patients as part of their routine medical evaluation. PMID- 26667713 TI - [FACTORS AFFECTING THE ABANDONMENT OF BREASTFEEDING IN A SUPPORT PROGRAM FOR THE SAME IN THE HOSPITAL FOR WOMEN, MORELIA MICHOACAN IN THE PERIOD FROM SEPTEMBER TO NOVEMBER 2014]. AB - INTRODUCTION: there are certain factors that influence the early cessation of breastfeeding among which are the demographic, cultural, biological and psychological. OBJECTIVE: to analyze sociodemographic factors influencing the abandonment of breastfeeding in a support group to it. METHODOLOGY: descriptive, prospective, observational, cross-sectional study at the Hospital for Women in Morelia Michoacan, from September to November 2014, a total of 86 women in the postpartum period gynecology floor. RESULTS: the reasons why the LME is abandoned are: age under 25 years (19.1%), urban locality (16.9%), and marital cohabitation (15.7%), and work (9%). CONCLUSIONS: most of the women had that age, education level and location are the main factors that influence as to abandon breastfeeding before the recommended time. PMID- 26667714 TI - ENERGY CONSUMPTION, THE DISTRIBUTION OF MACRONUTRIENTS AND BMI IN MOTHERS AND THEIR MEXICAN SCHOOLCHILDREN. AB - OBJECTIVE: to identify the association between the percentage of adequacy of energy and protein and the distribution of macronutrients and sugar in the diets of mothers and schoolchildren with their respective BMI. METHODS: in a cross sectional study, 174 5-12-year-old schoolchildren and their mothers were randomly selected. BMI was measured, and 24-hour dietary surveys were administered on weekdays and weekends. The associations between the dietetic indicators in the mothers and their children and the BMI of the mothers and their children were assessed. The chi-square test, linear regression and odds ratio were used for analysis. RESULTS: excessive energy consumption in the mothers increased the risk of excessive energy consumption in their daughters by 11-fold (p=0.04). Maternal lipid intake was associated with the consumption of lipids in their sons and daughters (p. PMID- 26667715 TI - ANDROGEN RECEPTOR CAG AND GGN REPEAT POLYMORPHISMS AND BONE MASS IN BOYS AND GIRLS. AB - INTRODUCTION: the human androgen receptor (AR) gene possesses two trinucleotide polymorphic repeats, (CAG and GGN) that affect the amount of AR protein translated. In this study, we genotyped these polymorphic tracts in a representative sample of Caucasian children (Tanner <= 5), 152 boys (11.5 ?} 2.6 yrs) and 116 girls (10.1 ?} 3.2 yrs) from Spain and investigated their association with bone mass. METHODS: the length of CAG and GGN repeats was determined by PCR and fragment analysis. Body composition was assessed by dual energy x-ray absorptiometry (DXA). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of <= 21 and CAG long (CAGL) if CAG > 21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of <= 23 and GGN long (GGNL) if GGN > 23. RESULTS: in boys, significant differences in height, body mass, whole body bone mineral density (BMD) and content (BMC), upper extremities BMC, lower extremities BMC, femoral neck BMD, Ward's triangle BMC and BMD and lumbar spine BMD were observed between CAGS and CAGL groups (P < 0.05). Thus, upper extremities BMD differed between GGNS and GGNL groups. After adjusting for confounding variables, only upper extremities BMD between GGNS and GGNL groups remained significant (P < 0.05). No differences were observed in girls in any measured site in relation to either CAG or GGN polymorphisms length. CONCLUSIONS: our results support the hypothesis that longer alleles of the AR CAG and GGN polymorphisms are associated with increased bone mass in prepubertal boys. PMID- 26667716 TI - EFFECTS OF AN INTERVENTION PROGRAM (HHP) ON THE PROMOTION OF HEALTHY HABITS IN EARLY ADOLESCENCE. AB - BACKGROUND: it is vital to monitor and promote healthy lifestyle habits in early adolescence, as it is a time of changes when future lifestyle habits are formed. METHODS: a study was conducted to find out the effects of a Healthy Habits Program (HHP) in children between the ages of 10 and 12 years (N = 158). The study included an intervention group (IG) (n = 90), which participated in the HHP for 8 months, and a control group (CG) (n = 100). In order to assess healthy habits in these children we used the Inventory of Healthy Habits (IHH), the reliability of which was previously evaluated (N = 134). RESULTS: the IHH obtained good reliability, Interclass Correlation Coefficient (range .506 - 884; p < .001) and Spearman Correlation Coefficient (range r = 529 - 884; p < .001). As regards the HHP, there were no differences in eating habits initially (p = .564), but by the end of the study (p = .001) the IG showed better habits. As for the other healthy habits indicators, the CG had better habits initially (p = .047), but the score of the IG improved and there were no differences between the groups at the end of the study. CONCLUSIONS: it was shown that the IHH is a suitable and reliable questionnaire for studying habits in adolescents. The HHP brought about changes in the IG, which achieved better scores for eating habits and sum of health habits. PMID- 26667717 TI - [INTESTINAL FAILURE IN PEDIATRIC PATIENTS: EXPERIENCE AND MANAGEMENT BY A MULTIDISCIPLINARY GROUP]. AB - BACKGROUND: institutions with multidisciplinary teams have shown improvements in patient outcomes with intestinal failure. Multidisciplinary approach allows an integral management and effective communication between families and care teams. OBJECTIVE: describe the multidisciplinary management and outcome in pediatric patients with intestinal failure. METHODS: retrospective study in patients 18 years old or less, with intestinal failure and Total Parenteral Nutrition (TPN) required. Simple frequencies and percentages were used for qualitative variables, and central tendency and dispersion measures were used for quantitative variables. RESULTS: 33 patients with a median follow up of 281 days were evaluated. The median duration of the TPN was 68 days and the mean of catheter related infections was 2.26 per patient. In 31 patients oral or enteral nutrition was provided, starting in 61.3% of cases through tube and continuous infusion. As concomitant treatment 72.7% of children received ursodeoxycholic acid, 67.7%, cholestyramine 57.6% loperamide, 48.5% antibiotics and 36.4% probiotic. The families of 24 patients were evaluated by social work professionals. Intestinal autonomy was achieved in 69.7% of cases, 72.7% of them showed an improvement in the score z of weight and showed an end albumin significantly higher than the initial (p value: 0.012). CONCLUSIONS: the management of patients with intestinal failure is a challenge for health institutions and require care based on a standardized protocol and a multidisciplinary group. PMID- 26667718 TI - PERINATAL OUTCOMES OF PREMATURITY AND BIRTH WEIGHT ACCORDING TO MATERNAL CAFFEINE CONSUMPTION. AB - Objetive: identify whether there is an increased risk of adverse perinatal outcomes, like prematurity or decreased weight in newborns, associated with caffeine consumption during the first half of pregnancy in pregnant women of our population. METHODS: transversal study carried out in 1 175 patients from Virgen de las Nieves University Hospital of Granada (Spain). Information about caffeine consumption during first half of gestation and perinatal outcomes was obtained by personal interview, medical records and telephone call after delivery. The average caffeine intake was calculated from meals and drinks included in a validated questionnaire. RESULTS: there was no difference in caffeine consumption in pregnant women with birth weight >=2 500 g and. PMID- 26667719 TI - [NORMATIVE VALUES OF SF-6D QUESTIONNAIRE FOR CHILEAN DIABETES PATIENTS]. AB - INTRODUCTION: diabetes mellitus is a chronic disease with a great prevalence and economic impact worldwide. Diabetes has an impact on health-related quality of life. The SF-6D is a well-known preference-based questionnaire that allows assessing health-related quality of life. It is one of the most used worldwide because it allows knowing the social preferences derived from different states of health. However, to our knowledge, normative values of this questionnaire in Chilean diabetic population are not available. OBJECTIVE: to report normative data of the SF-6D in Chilean diabetic population. METHODS: data were taken from the National Health Survey (ENS 2009-2010) of Chile. In this study, 424 people who have diabetes (143 men and 281 women) were included. The data have been presented stratified by sex and age group, and by region, marital status, smoking, income and education. RESULTS: the global utility index was 0.70 (+/- 0.15) in men and 0.65 (+/- 0.15) in women. Only 5% of population declared having a utility "1". The utility index of the SF-6D in patients with diabetes decreases with age, in situations of low-income, low education levels. CONCLUSIONS: this study reports the normative values of the SF-6D utility index in Chilean diabetic population. PMID- 26667720 TI - APOLIPOPROTEINS AND THEIR ASSOCIATION WITH CARDIOMETABOLIC RISK BIOMARKERS IN ADOLESCENTS. AB - INTRODUCTION: the apoB/apo A-I ratio has been reported as an important predictor of cardiovascular risk, being superior to lipids, lipoproteins and conventional lipid ratios. OBJECTIVE: to investigate the association between apolipoproteins A I and B, and the apolipoprotein B/apolipoprotein A-I ratio and cardiometabolic risk variables in adolescents. METHODS: this was a cross-sectional study including 104 adolescents of public schools in Recife during the months of March/April, 2013. Sociodemographic, anthropometric, clinical and biochemical variables were analysed. The apolipoproteins were analysed via Immunoturbidimetry. RESULTS: body mass index, waist circumference, waist circumference/height, triglycerides, cholesterol/HDL, and apolipoprotein B/apolipoprotein A-I declined with the progress of the percentile distribution of apolipoprotein A-I concentrations, while the HDL and apolipoprotein B increased between the first and last quartiles of the apolipoprotein A-I concentrations. Systolic blood pressure, body mass index, waist circumference, waist circumference/height, cholesterol, LDL, triglycerides, cholesterol/HDL, and LDL/HDL increased progressively in the quartile distribution of the concentrations of apolipoprotein B and apolipoprotein B/apolipoprotein A-I. Alfa 1-acid glycoprotein serum levels increased hand-inhand with the percentile progression of apolipoprotein B. CONCLUSIONS: the findings underline an important association of apolipoproteins A-I and B, and the apolipoprotein B/apolipoprotein A-I ratio and their clinical, biochemical and anthropometric cardiometabolic risk. However, prospective studies are important to evaluate the pertinence of implementing these markers in the clinical practice. PMID- 26667721 TI - [PREVALENCE OF METABOLIC SYNDROME AMONG THE STAFF OF UNIVERSIDAD INTERNACIONAL DEL ECUADOR, HEADQUARTERS, PERIOD 2014-2015]. AB - INTRODUCTION: metabolic syndrome is a group of metabolic abnormalities that increase the risk of developing type 2 diabetes and cardiovascular disease. There are several criteria for diagnosis; the most used are the International Diabetes Federation (IDF) and the Adult Treatment Panel III (ATP III). An early treatment may prevent its associated complications and improve the quality and life expectancy of the person; it must be focused on changes in lifestyle such as healthy eating and regular physical activity. OBJECTIVE: to determine the prevalence of metabolic syndrome according to the diagnostic criteria of the International Diabetes Federation (IDF) and the Adult Treatment Panel III (ATP III) Methodology: it was a cross-sectional study in which participate 128 people (55 women and 73 men) aged between 18 and 75 years, who were given a nutritional history, anthropometric measures and biochemical tests. RESULTS: the prevalence of overweight was 63% (48% overweight and 15% obese). The prevalence of metabolic syndrome according to IDF was 15.6% and 14.8% according ATPIII. CONCLUSIONS: among the employees is clear the high prevalence of overweight and metabolic syndrome. So it is a priority to work on the implementation of preventive measures to stop this trend and cardiometabolic disorders. PMID- 26667722 TI - ASSOCIATION BETWEEN DAILY SITTING TIME AND PREVALENT METABOLIC SYNDROME IN AN ADULT WORKING POPULATION: THE AWHS COHORT. AB - OBJECTIVE: the aim of this analysis was to measure the association between daily sitting time and prevalent metabolic syndrome, independently of the physical activity performed. SUBJECTS AND METHODS: the Aragon Workers' Health Study cohort consists of 5 865 participants from which a sample of 1 415 male participants (40 55 years old) with completed data at baseline was selected. Sitting time and physical activity were assessed by validated questionnaires, and the socio demographic, clinical and biochemical covariates needed to diagnose metabolic syndrome were collected as part of the study protocols. Metabolic syndrome was defined according to the modified National Cholesterol Education Program - Adult Treatment Panel III. Multiple linear and logistic regression models were carried out to quantify this association using sitting time categorized into tertiles. RESULTS: mean sitting time was 5.78 +/- 1.72 h/day, and the prevalence of metabolic syndrome was 19.2%. Comparing participants in the highest (> 6.57 h/day) versus lowest (1.85-4.57 h/day) tertile of sitting time, a positive association was observed for metabolic syndrome (OR 1.77, 95%CI: 1.25-2.49) and triglyceride (OR 1.70, 95%CI: 1.30-2.24), HDL-cholesterol (OR 1.65, 95%CI: 1.06 2.58), waist circumference (OR 1.57, 95%CI: 1.17-2.11) and fasting blood glucose (OR 1.35, 95%CI: 1.03-1.77) criteria, adjusting the level of physical activity. CONCLUSIONS: higher sitting time is associated with an increased prevalence of metabolic syndrome independently of physical activity performed. These results could be useful to carry out effective strategies for cardiovascular health promotion especially in workplaces. PMID- 26667723 TI - SUITABILITY OF VISCERAL ADIPOSITY INDEX AS A MARKER FOR CARDIOMETABOLIC RISKS IN JORDANIAN ADULTS. AB - INTRODUCTION: visceral adiposity index (VAI) has recently been proposed as a predictor of cardiometabolic risk, but its usefulness has not been confirmed. OBJECTIVES: to evaluate the association between VAI and conventional adiposity and cardiometabolic risk indices and examine VAI risk predictive ability and compare it with other adiposity indices. METHODS: a total of 1 622 Jordanian adults, 686 men and 936 women, aged 20-80 years were included this study. VAI, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist height ratio (WHtR) were examined and high-density lipoprotein cholesterol (HDL C), triglycerides (TG), fasting serum glucose (FSG), systolic (SBP), and diastolic (DBP) blood pressure were determined. Associations and age-and gender specific distribution and differences were evaluated. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used for risk predictive ability comparison. RESULTS: VAI of women (6.82+/-6.43) was higher than of men (4.15+/-4.62). VAI severity increased with age in a dose-response trend (p<0.001) in both genders. Women had higher prevalence than men of high risks of VAI and all adiposity and cardiometabolic indices. VAI markedly associated with TG, HDL-C, FSG, SBP and DBP or WHR, WC, WHtR and BMI in respective order of correlation potency for cardiometabolic or adiposity risk indices. In men and women respectively, the largest AUC was for VAI (0.79 vs. 0.77), followed by WHR (0.73 vs. 0.75), WC (0.69 vs. 0.74), WHtR (0.65 vs. 0.71) and BMI (0.53 vs. 0.51). CONCLUSIONS: the findings suggest that VAI potentially associates with cardiometabolic risks and proves to be superior to other adiposity indices in predicting such risk. PMID- 26667724 TI - [EFFECT OF A BEVERAGE MADE FROM CACTUS PEAR (NOPALEA COCHENILLIFERA (L) SALM DYCK) IN A RURAL POPULATION OF HIDALGO, MEXICO; A PILOT CLINICAL TRIAL]. AB - INTRODUCTION: cactus pear has been used in Mexican traditional medicine. However, clinical studies are limited to demonstrate the effectiveness as anti-diabetic. OBJECTIVE: to evaluate the effect of a fresh beverage made from Nopalea cochenillifera (l.) Salm-dyck on glucose levels, glycosylated hemoglobin, weight, waist circumference and blood pressure. METHODS: the beverage (50 g/250 mL) was daily administered in twenty patients for 30 days. RESULTS AND DISCUSSION: differences statistically significant were found in some time of the supplementation for all measured variables excepting for glucose levels, this suggests that values might be significant to a longer administration or bigger doses. CONCLUSIONS: although preliminary data, the results demonstrated that cactus pear used in this study may be an alternative for the management of patients with diabetes type 2. Nevertheless, further trials must be conducted with a bigger sample size and more control groups so that the effectiveness can be fully evaluated. PMID- 26667725 TI - [METABOLIC SYNDROME AND CARDIOVASCULAR RISK IN PATIENTS WITH SCHIZOPHRENIA, BIPOLAR DISORDER AND SCHIZOAFFECTIVE DISORDER]. AB - INTRODUCTION: patients with severe mental ilness such as schizophrenia, schizoaffective disorder and bipolar disorder die at least 20 years earlier than general population. Despite preventive strategies, cardiovascular disease is the first cause of death. OBJECTIVES: analyse the percentage of patients with a high body mass index, metabolic syndrome and their cardiovascular risk at 10 years in patients with a diagnosis, based in DSM-IV criteria for schizophrenia, schizoaffective disorder or bipolar disorder. These patients were hospitalized because and acute condition of their mental ilness in the Brief Hospitalization Unit of Hospital Universitario de Mostoles between November of 2014 and June of 2015. MATERIAL AND METHODS: in 53 patients, 34 with a diagnosis of schizophrenia, 16 with a diagnosis of bipolar disorder and 3 with a schizoaffective disorder, weight, size abdominal perimeter measures and blood pressure were collected. The body mass index was assesed. Blood tests were taken and we use sugar, triglycerides, total cholesterol and HDL cholesterol levels as paramethers for the ATP III and Framingham criteria. We also review the clinical history of the patients and lifestyle and use of toxic substances were registered. RESULTS: 51% of the patients were men and 49% were women. The average age was 40. 38% of the patients were overweighed, 22% obese and 4% had morbid obesity. 26% of the patients had metabolic syndrome, the clinical evolution of the majority of these patients was of more tan 10 years and they also have been treated with different antypsychotics and antidepressants. Using the Framingham criteria, 11% of the patients had a cardiovascular risk higher than 10 % in the next 10 years. CONCLUSIONS: overweight and its consequences in patients with a severe mental ilness are intimately related with their lifestyle, disparities in the access to health resources, the clinical evolution of the disease and pharmacotherapy. Strategies to promote physical health in these patients in the spanish health sistme are insufficient. PMID- 26667726 TI - GLUCOMANNAN AND GLUCOMANNAN PLUS SPIRULINA-ENRICHED SQUID-SURIMI ADDED TO HIGH SATURATED DIET AFFECT GLYCEMIA, PLASMA AND ADIPOSE LEPTIN AND ADIPONECTIN LEVELS IN GROWING FA/FA RATS. AB - Type 2 diabetes is a very prevalent chronic disease. Among dietary factors for its prevention and treatment, interest has grown in satiating fibre (konjac glucomannan) and spirulina. Our previous studies suggest that glucomannan itself and/or in conjunction to spirulina displayed hypolipemic and antioxidant effects when incorporated to squid surimi as functional ingredients. The present study aims to determine whether glucomannan- enriched or glucomannan plus spirulina enriched squid-surimi improve plasma glucose and insulin levels in Zucker fa/fa rats fed a high saturated fat diet. Twenty four growing rats, divided into three groups, were given modified AIN-93M diets for seven weeks: 30% squid-surimi control diet (C), 30% glucomannan-enriched squid-surimi diet (G) and 30% glucomannan plus spirulina-enriched squid-surimi diet (GS). All rats became hyperglycemics and hyperinsulinemics, but G and GS diets induced significantly lower glucose levels (20%; p < 0.05) but did not modify insulinemia with respect to C diet. GS animals showed higher HOMA-D (p < 0.05) than C ones suggesting increased insulin availability. Plasma leptin and adiponectin decreased in G and GS vs. C group (p < 0.05). Adipose adiponectin increased significantly in G and GS vs. C rats (16-20 times, p < 0.01). Leptin in adipose tissue was higher in GS vs. G group (p < 0.05). In conclusion, both glucomannan-diets were able to reduce hyperglycemia and increase adipose tissue adiponectin levels in fa/fa rats, suggesting an anti-hypertrophic and insulin-sensitizing adipokine effect in this tissue. Spirulina inclusion increased insulin availability. Although results are promising, the utility of consuming glucomannan surimis as part of usual diets demands future studies. PMID- 26667727 TI - SELENIUM IN DYSPHAGIC PATIENTS WHO UNDERWENT ENDOSCOPIC GASTROSTOMY FOR LONG TERM ENTERAL FEEDING. AB - BACKGROUND AND AIMS: endoscopic gastrostomy (PEG) patients usually present protein-energy malnutrition, but little is known about selenium deficiency. We aimed to assess serum selenium evolution when patients underwent PEG, after 4 and 12 weeks. We also evaluated the evolution of albumin, transferrin and Body Mass Index and the influence of the nature of the underlying disease. METHODS: a blood sample was obtained before PEG (T0), after 4 (T1) and 12 (T3) weeks. Selenium was assayed using GFAAS (Furnace Atomic Absorption Spectroscopy). The PEG patients were fed through homemade meals. Patients were studied as a whole and divided into two groups: head and neck cancer (HNC) and neurological dysphagia (ND). RESULTS: we assessed 146 patients (89 males), between 21-95 years old: HNC-56; ND 90. Normal values of selenium in 79% (n=115); low albumin in 77, low transferrin in 94, low values for both serum proteins in 66. Low BMI in 78. Selenium has slow evolution, with most patients still displaying normal Selenium at T3 (82%). Serum protein levels increase from T0 to T3, most patients reaching normal values. The nature of the underlying disease is associated with serum proteins but not with selenium. CONCLUSIONS: low serum selenium is uncommon when PEG is performed, after 4 and 12 weeks of enteral feeding and cannot be related with serum proteins levels or dysphagia cause. Enteral nutrition using customized homemade kitchen meals is satisfactory to prevent or correct Selenium deficiency in the majority of PEG patients. PMID- 26667728 TI - [STRATEGIES TO IMPROVE THE NUTRITIONAL AND HEALTH CHARACTERISTICS OF MEAT PIE OF MURCIA]. AB - OBJECTIVES: improvement of the nutritive quality and healthy properties of the meat pie of Murcia (MMP), maintaining its appreciated organoleptic quality and the design of a functional MMP through the addition of a natural ingredient rich in fructooligosaccharides. METHODS: different formulations of the MMP (healthy MMP and functional MMP) have been elaborated by changing the type and amount of some of its ingredients. The nutritional composition, the caloric value, the fatty acid profile and the fat quality have been determined. Different sensory attributes have been evaluated together with the global acceptance using a descriptive scale and an hedonic scale respectively. RESULTS AND DISCUSSION: the healthy MMP presents a lower energy content (15.4%), total fat (39%), saturated fat (48%) and salt (45%), and a decrease of the potential atherogenic (27%), trombogenic (30%) and hipercholesterolemic (30%) indexes than the traditional product. Among the four amounts assayed (2.5, 5, 10 y 15%), only the substitution with 2.5 and 5% of the functional ingredient, did not diminish the global acceptance of the functional MMP when compared to the traditional one. CONCLUSIONS: the changes in the formulation have improved the nutritive composition and the healthy characteristics of the traditional MMP, keeping its organoleptic quality. The functional MMP elaborated with the functional ingredient at 5% represents an improvement in the functional characteristics of the studied food. These strategies contribute to the maintenance of this type of traditional foods, avoiding the lose of culture, identity and gastronomic heritage of Spain and in particular in the Region of Murcia. PMID- 26667729 TI - [MEDICAGO SATIVA L: IMPROVEMENT AND NEW APPROACHES OF ITS NUTRITIONAL AND FUNCTIONAL VALUE BY BACTERIAL CO-INOCULATION]. AB - OBJECTIVE: to study the effect of co-inoculation with Ensifer meliloti and Halomonas maura of the leguminous Medicago sativa L., on growth, nutritional and functional value, grown under salinity conditions. METHODS: plants of M. sativa were grown in a solution with a mixture of salts (CaSO4, MgCl, NaCl and NaHCO 3) and were co-inoculated with its specific rhizobium and the halophilic moderated bacterium H. maura. Different physiologic parameters were determined, as well as, nitrogen and minerals content. Furthermore, an assay of in vitro digestibility was carried out. RESULTS: salinity had a negative effect on the plants; however, co-inoculation increased yield, nitrogen content, total minerals, Ca and Mg. Moreover, physiologic parameters as water potential and leghemoglobin content in fresh nodules were higher compared to those of plants inoculated only with E. meliloti. Both, salinity and bacterial treatment with E. meliloti and H. maura increased the antioxidant capacity of the legume, in dialyzates and retentates collected after an in vitro digestibility assay. CONCLUSION: co-inoculation of plants with E. meliloti and H. maura could improve the alfalfa yield under specific salinity conditions, increasing the nutritional and functional value of the plants. M. sativa could be considered in the formulations of nutritional supplements for the human diet. PMID- 26667730 TI - [ADHERENCE TO THE MEDITERRANEAN DIET AND HYDRATION IN SPANISH AND MOROCCAN POPULATIONS]. AB - INTRODUCTION: southern European, Middle Eastern, and North African countries bordering the Mediterranean share dietary habits characterized by moderation and a variety of foods, notably fruit and vegetables. These customs are becoming modified due to social and economic changes. An adequate intake of water and other drinks is essential for a healthy diet. OBJECTIVE: to study adherence to the Mediterranean Diet (MD) and bottled water/beverage consumption in two Mediterranean populations. METHODS: adults from North-Western Morocco and Southern Spain (n = 400) completed a semi-quantitative food frequency questionnaire. The bottled waters they reported were then purchased locally (17 brands in Morocco, 30 in Southern Spain) for ionic-exchange chromatography study. RESULTS: cation values (mg/L) ranged from 140.16 to 439 for C, 53.15 to 87.5 for Mg, 1169.78 to 257.2 for Na, and 50.26 to 26.5 mg/L for K, i.e. waters with medium mineralization levels. No cation supplied > 7% of the recommended dietary allowance (RDA) in either population. MD adherence was higher in the Spanish (6.28 +/- 1.38) versus Moroccan (4.42 +/- 1.52) population. There is a substantial intake of water through the MD due to its elevated fruit/vegetable content. Consumption of bottled water, infusions, and juices was higher in the Moroccan population; consumption of beer and other alcoholic drinks was higher in the Spanish population. The total liquid consumption was higher in the Moroccan population. The drinks intake profile permits classification of the populations, with odds ratios ranging from 1.6 to 11.01 for a higher intake of juices, soft drinks, tea, bottled water, and total liquids in the Moroccan versus Spanish population. PMID- 26667731 TI - AGREEMENT BETWEEN DIFFERENT EQUATIONS TO ESTIMATE OSMOLARITY OF PARENTERAL NUTRITION SOLUTIONS. AB - BACKGROUND: our aim was to measure the osmolality of several PN formulas at different component concentrations to determine if equations described in literature to calculate osmolarity accurately predict osmolalality in other experimental conditions different than these used to develop them. METHODS: osmolality of 12 different types of PN solutions, 9 for central and 3 for peripheral perfusion were measured by using freezing point depression in cross sectional study. We evaluated the agreement (Pearson correlation test) and differential bias between measured osmolality and calculated osmolarity for three different equations described in the literature: Pereira Da Silva, ASPEN Practice Manual and ASPEN guidelines. RESULTS: mean +/- SD osmolality of PN solutions was 1789 +/- 256 (range 1 540 - 2 372) and 751 +/- 64 mOsm/kg (range 689 - 817) for central and peripheral infusion, respectively. The osmolality of PN formulations was mainly due to glucose (r = 0.975) and amino acids (r = 0.948). All studied equations had a good correlation in the bivariate analysis (p = 0.000). All equations had a trend to underestimate the osmolality compared with the measured value. However, ASPEN guidelines equation overestimated the osmolality for peripheral PN. CONCLUSIONS: measurement of osmolality of peripheral PN solutions is important to reduce the risk of phlebitis. The different equations described previously show a good correlation between them although in general underestimate the osmolality. PMID- 26667732 TI - EPITOPE-BASED VACCINE FOR THE TREATMENT OF DER F 3 ALLERGY. AB - INTRODUCTION: mites allergic asthma is caused by exposure to home dust mite (HDM). Der f 3 is believed to be one of the major allergens in mites allergic asthma. The work was to identify the immune characteristics of Der f 3 epitope based vaccine containing T cell and B cell epitopes. METHODS: T cell lines were generated from peripheral blood mononuclear cells of Der f 3 allergic patients. Three T cell epitopes and five B cell epitopes of Der f 3, which we identified previously, were selected to design a polypeptide (named Der f3-peptides). DNA constructions encoding these Der f 3-peptides were expressed in Escherichia coli. The T cell lines were stimulated with the peptides and tested for proliferative capacity and cytokine production. RESULTS: plasmid pET28a (+)-Der f 3-peptides was constructed and expressed in E. coli BL21, and the Der f3-peptides protein was purified and confirmed by Western blotting. The Der f 3-peptides were recognized by the T cell clones from allergic patients. SI value of Der f 3 group and Der f 3-peptides group were both higher than that of PBS group (P<0.05). The Der f 3 and Der f 3 peptides induced secretions of IL-4 and IL-5 were decreased compared with that of PBS group (P<0.05). The capacity of IgE-binding to Der f 3 peptides (41.25+/-5.67) MUg/ml was decreased dramatically compared with that of Der f 3 (83.60 +/- 10.92) MUg/ml (P < 0.05). CONCLUSIONS: our results demonstrate that several major T cell epitopes and B cell epitopes of Der f 3 can be valuable for designing the peptide-based immunotherapeutics for the mites allergic asthma. PMID- 26667733 TI - PROKARYOTIC EXPRESSION AND BIOACTIVITY EVALUATION OF THE CHIMERIC GENE DERIVED FROM THE GROUP 1 ALLERGENS OF DUST MITES. AB - BACKGROUND: we successfully reconstituted the gene from group 1 allergens of dust mites, and obtained a body of shuffled genes. In order to verify the prediction on the chimeric gene, we tentatively cloned R8 into the vector that was prokaryoticly expressed, purified and assessed for its bio-activities. METHODS: the expressed product was detected by SDSPAGE and the target protein was purified. The purified protein R8 was detected by ELISA. 75 BALB/c mice were divided into 5 groups, namely PBS, rDer f1, rDer p1, R8 and asthma group. The mice were treated with dust mite allergens at 0, 7, 14 day by intraperitoneal injection and inhaled challenge as aerosol on day 21 for 7 days. Specific allergen immunotherapy was performed using rDer f1, rDer p1 and R8 allergens respectively. The level of IFN and IL- 4 in BALF was detected by ELISA. RESULTS: the chimeric gene R8 was expressed with a band of approximately Mr 35000. Compared with groups of rDer f 1 and rDer p 1 [(80.44+/-15.50) and (90.79+/ 10.38) MUg/ml respectively], IgE binding capacity of the protein R8 (37.03+/ 12.46) MUg/ml was statistically lower (P<0.001). The level of IFN in sera of R8 group [(343.43+/-38.79) pg/ml] was higher than that of the PBS and asthma groups [(393.93+/-50.68) and (208.44+/-46.11) pg/ml respectively] (P<0.01), but no statistical difference to that of the rDer f 1 and rDer p 1 groups (P>0.05). IL-4 level in R8 group was lower markedly than the others (P<0.05 or P<0.01). CONCLUSIONS: chimeric protein R8 derived from the group 1 allergens of dust mites has been expressed with low allergenicity and high immunogenicity. PMID- 26667734 TI - [VITAMIN D AND ITS RELATION WITH THE ANATOMICAL LOCATION OF HIP FRACTURE IN CHILEAN OLDER ADULTS HOSPITALIZED]. AB - INTRODUCTION: in older adults, deficit of Vitamin D and hip fractures are common. There exists relationships between both conditions, and it have been shown that supplementation of Vitamin D improve prognosis of hip fractures. In the case of Chile, information about relationship between Vitamin D and hip fractures is scarce. OBJECTIVE: quantify plasma levels of vitamin D and relate them to the anatomical location of hip fracture. METHODS: cross-sectional study. 222 Chilean adults >=60 years, hospitalized for hip fracture between June, 2014 and June, 2015. We use data of medical records about gender, age, seasonality and anatomical location of hip fracture (intra and extracapsular). We measure plasmatic levels of Vitamin D (PLVD) and glomerular filtration rate (GFR) (MDRD 6). Kolmogorov-Smirnov test and non-parametric test were used. For determine relations between PLVD and anatomical location we use linear regression. RESULTS: there was a predominance of women (80.6%). The average age was 80.7 years (SD=7.8). Intracapsular hip fractures were 43.2%. 80% of the sample presents Vitamin D in deficitary levels (n = 180). PLVD average was 13.3 ng/cc (SD=6.7), in subjects with intracapsular fractures were significantly lower (p<0.001). CONCLUSIONS: PLVD in subjects with hip fracture should be monitored, as there are differences according to anatomical location of the fracture. This precedent could favor the treatment and recovery of subjects presenting for the first time hip fracture. PMID- 26667735 TI - [NUTRITIONAL AND SOCIODEMOGRAPHIC FACTORS IN PARKINSON'S DISEASE: RURAL VIEW]. AB - Parkinson's disease (PD), its prevalent in population to 65 years of age, nevertheless can occur earlier. Patients with PD exhibit motor and no motor symptoms these may relate with changes in nutritional habits during disease progression. The prevalence of PD and nutritional factor could be different in rural areas compared to urban regions and can be associated with sociocultural and demographic features. It has been suggested a possible association between excessive intake of saturated fats and low consumption of vitamins such as B6 with EP, however, the results are still not conclusive. Some of significant factors could affect nutritional habits and status in PD in rural areas, are: health status, economic availability, environmental and geographical factors, among others. This review presents some eating habits and sociodemographic factors in PD principally in rural areas. PMID- 26667736 TI - [EFFECT OF OVERWEIGHT AND OBESITY ON THE EQUILIBRIUM TIME, BUT NO IN THE TOTAL BODY WATER AND BODY COMPOSITION COMPARTMENTS IN WOMEN SUBJECTS OVER 60 YEARS OF AGE]. AB - INTRODUCTION: aging and obesity cause changes in water exchange rate, which could affect the equilibrium time of deuterium oxide (2H2O). OBJECTIVE: to assess the effect of overweight and obesity on the equilibrium time of the stable isotope deuterium in saliva samples of older adults. METHODS: a sample of 18 women over 63 years with a body mass index (BMI) of 20.8 to 40.5 kg/m2 were included. A basal saliva sample was took and immediately a dose of 30 g of 2H2O was administered orally. Saliva samples at 2, 2.5, 3, 3.5 and 4 hours post-dose were taken. Deuterium in saliva samples were analyzed by Fourier Transform Infrared spectroscopy technique. RESULTS: the average in equilibrium time (plateau) in women of normal BMI (18.5-24.9 kg/m2) was 3.6 +/- 0.2 hours, which was statistically different to those obtained in the group with overweight (25-29.9 kg/m2) and obese (>30 kg/m2) of 2.9 +/- 0.4 hours and 2.8 +/- 0.4 hours, respectively (p0.05). CONCLUSION: obesity had an effect on the equilibrium times; however, did not affect the calculation of total body water and body composition in this older women adult group. PMID- 26667737 TI - [RELEVANCE OF A PROGRAM BALANCE IN HEALTH-RELATED QUALITY OF LIFE OF OBESE ELDERLY WOMEN]. AB - OBJECTIVE: the objective of this study was to analyze the effects of a specific intervention program of strength and balance in the quality of life in obese women elderly. MATERIAL AND METHODS: a total of 56 obese women elderly (average 67.2 +/- 2.1 age) were randomized into control group (28) and experimental (28). The experimental group carried out an exercise program based on balance and lower body strength, for 24 weeks. Balance and strength was measured before and after the intervention. Similarly, the perception health-related quality of life (HRQOL) was determined using SF-36 . RESULTS: the experimental group showed a significant improvement in all tests. In the test of the chair was observed an increase of 28.3% after the program (P <0.05). The test countermovement jump (CMJ) reflected an improvement of 20.8% (P <0.001). Equally positive changes were detected in the test of balance with closed eyes (P <0.001). However, the significance level with open eyes was lower than with closed eyes (P <0.05). Also, was observed a significant improvement in the experimental group on monitoring in all dimensions of SF-36. CONCLUSION: a specific program of balance produces positive changes in the stability of a sample of obese women elderly, significantly improving HRQOL in all dimensions, emphasizing physical health and social function and mental health mental components. Are opened new avenues for greater welfare of obese women elderly. PMID- 26667738 TI - VALIDATION AND COMPARISON OF EQ-5D-3L AND SF-6D INSTRUMENTS IN A SPANISH PARKINSON'S DISEASE POPULATION SAMPLE. AB - INTRODUCTION: generic, preference-based Health- Related Quality of Life instruments are receiving growing attention in health-care decision-making process. In spite of this, to our knowledge, EQ-5D and SF-6D have never been compared in a Parkinson's disease population sample. OBJECTIVE: the aim of this paper was to assess the psychometric properties of both instruments in a Spanish PD population sample. METHODS: a total sample of 133 patients were interviewed using EQ-5D-3L and SF-6D. The validity, level of agreement and sensitivity of both instruments were computed and then compared. The Spanish tariff has been used in both instruments. RESULTS: utilities of EQ-5D-3L and SF-6D have shown a strong correlation (r >0.50 and p<0.001) with the summary score of the PDQ-8 and the EQ-VAS score. Significant differences were observed in the stages III-IV of the Hoehn & Yahr stage. SF-6D had 51% higher efficiency than EQ-5D at detecting differences in symptoms severity. DISCUSSION: both EQ-5D-3L and SF-6D seem to be adequate generic Health-Related Quality of Life measures in terms of validity and sensitivity. CONCLUSION: EQ-5D-3L presents greater ceiling and floor effects than the SF-6D instrument in this sample. Besides, the instrument SF-6D was better at detecting changes in symptoms severity compared with EQ-5D-3L. PMID- 26667739 TI - [COCONUT OIL: NON-ALTERNATIVE DRUG TREATMENT AGAINST ALZHEIMER'S DISEASE]. AB - BACKGROUND: Alzheimer's dementia is the most prevalent nowadays. As for treatment, there is no definitive cure drug, thus new therapies are needed. In this regard the medium chain triglycerides are a direct source of cellular energy and can be a nonpharmacological alternative to the neuronal death for lack of it, that occurs in Alzheimer patients. OBJECTIVE: to evaluate the impact of coconut oil in the development of Alzheimer's dementia, in any degree of dementia. Also determine whether this improvement influences within variables such as sex and suffering or not Type II Diabetes Mellitus. MATERIAL AND METHODS: a prospective study was conducted in patients with Alzheimer's dementia, with a control and an intervention group which was administered 40 ml/day of extra virgin coconut oil. The parameters evaluated were the mini test scores Lobo cognitive test, pre and post intervention in both groups. RESULTS: it was observed in subjects taking the product, a statistically significant increase in test score MECWOLF and therefore an improvement in cognitive status, improving especially women's, those without diabetes mellitus type II, and severe patients. CONCLUSION: this study, although preliminary, demonstrated the positive influence of coconut oil at the cognitive level of patients with Alzheimer's, this improvement being dependent on sex, presence or absence of diabetes and degree of dementia. PMID- 26667740 TI - [NUTRITIONAL STATUS BY ANTHROPOMETRIC AND BIOCHEMICAL PARAMETERS OF COLLEGE BASKETBALL PLAYERS]. AB - INTRODUCTION: in relation to the student population, their class schedules, hours of study, budget shortages, among others, do not allow them to have good eating habits and sedentary ago. Within this context are the sports teams, which must deal with the above. OBJECTIVE: knowing the nutritional status of a group of college basketball players (BU) by anthropometric and biochemical parameters. METHODS: the research provides a non-experimental, descriptive, transversal, with a quantitative approach The sample was selected on a non-probabilistic approach. which included 12 players design. Anthropometric parameters for body mass index (BMI), somatotype and body composition was assessed. For biochemical glucose, triglycerides and cholesterol. RESULTS: have a BMI of 24.6 (kg/m2), are classified as endomesomorfas (5,5-4,3-1,2) have a fat mass 39.9% and 37.8% of muscle mass, glucose values are 68.7 (mg/dl), triglycerides 128 (mg/dl) and 189 cholesterol (mg/dl). CONCLUSION: the BU have normal values for BMI and biochemical parameters, but dig deeper greater amount of adipose tissue is found as reported by body composition and somatotype, a situation that could be related to poor eating habits, however is required further study to reach a categorical conclusion. PMID- 26667741 TI - [SLEEP QUALITY, EXCESSIVE DAYTIME SLEEPINESS AND INSOMNIA IN CHILEAN PARALYMPIC ATHLETES]. AB - INTRODUCTION: the sleep takes part in diverse biological and physiological functions, associating his restriction, with minor performance in the sport, nevertheless the quantity and quality of sleep is not known in paralympic athletes. OBJECTIVE: to determine the sleep quality, insomnia and excessive daytime sleepiness in Chilean paralympic athletes. METHODS: descriptive transverse Study, the sample included 33 paralympic athletes (24.2% women), those who were practicing swimming, tennis of table, football 5, powerlifting and tennis chair. The studied variables measured up across two surveys of dream: the Questionnaire of Insomnia and the Pittsburgh Sleep Quality Index. RESULTS: the paralympic athletes sleep were 6.9 ?} 1.4 hours, 27.7% presents daytime sleepiness, 69.6 % insomnia (Survey of insomnia =7), whereas 78.7 % exhibits a bad sleep quality. The age showed a positive correlation with latency to the sleep (r=0.417 *), the insomnia with latency to the sleep (r=0.462 **), the Pittsburg score was correlated negatively by the sleep duration (r =-0.323) and latency to the sleep is correlated positively by the Pittsburgh score (r=0.603 **). CONCLUSION: the chilean paralympic athletes, present a low sleep quality, insomnia and excessive daytime sleepiness, situation that might influence negatively the sports performance. PMID- 26667742 TI - [LIFESTYLES AND FACTORS ASSOCIATED TO NUTRITION AND PHYSICAL ACTIVITY AMONG ADOLESCENTS]. AB - INTRODUCTION AND OBJECTIVES: the objective of this work was to know the lifestyles of adolescent of the South of Spain related to nutrition and physical activity and the risk and protection factors associated. METHODS: a cross sectional correlational study was carried out with 204 adolescents enrolled at high schools. Descriptive, bivariate and multivariate analysis using regression models were performed (?=0.05). RESULTS: 63.7% had breakfast every day during the week (i.e. from Monday to Friday). They consumed more than six times a week: milk or dairy (56.3%), cereals (44.1%), fruits (40.7%), vegetables (28.5%), and soft drinks (24.5%). They did physical activity, at least 60 minutes, an average of 4.34 days a week, the body mass index stood at normal weight (19.85). By means of linear multivariate models we tested the influences of age, gender, and socio economic status on body max index, fruit and vegetable consumption and physical activity frequency of adolescents. CONCLUSIONS: knowing the inequalities in nutrition and physical activity area of adolescents, as well as the risk factors or health determinants can help to stablish specific different strategies and public health policies, targeted to these determinants of health, which can be developed at normative level and by means of interventions of nutritional health and physical activity promotion. PMID- 26667743 TI - IMBALANCES IN PROTEIN METABOLISM IN CRITICAL CARE PATIENT WITH SYSTEMIC INFLAMMATORY RESPONSE SYNDROME AT ADMISSION IN INTENSIVE CARE UNIT. AB - BACKGROUND: trauma and severe infections cause remarkable metabolic changes in patient with SIRS from an adaptive response aimed to control the underlying disease, repairing damaged tissue, and to synthesize substrates. If the attack is intense and sustained and the patient has a compromised nutritional status, can evolve into multiple organ failure and death. OBJECTIVE: assessment of nutritional proteic status and the involvement of proteins and inflammatory factors in critically ill patients. METHOD: multicenter observational analytical study in critical ill patients at the admission in ICU. RESULTS AND DISCUSSION: patients showed disturbances in clinical nutritional parameters which confirm their hypercatabolic situation, showing malnutrition state at admission, where 42.9% had plasma levels below the reference prealbumin. Amino acid profile was situated below the reference values and 99% of patients had low plasma transferrin. Significant differences were observed in total protein, ferritin and transferrin parameters adjusted by CRP levels, being higher when patients presented high inflammation in the case of ferritin and the opposite for the rest of parameters. Adjusting APACHE and SOFA scores according to low, medium and high severity, results showed significant differences in creatinine, urea, and transferrin, being lower at high severity grade for the last one. CONCLUSION: critical illness is characterized by a high degree of stress and accelerated degradation of proteins that cause malnutrition, systemic inflammation and organ dysfunction, with a significant association between albumin, ferritin and transferrin. PMID- 26667744 TI - [MODEL FOR ESTIMATING STANDING HEIGHT IN MEXICAN ADULTS FOR 20-59 YEARS, BASED ON KNEE LENGTH]. AB - Currently, bone distances are used to predict standing height in adults that might not be able to achieve a correct standing position. Knee length based algorithms for estimating standing height have been proposed and designed for specific populations. However, equations for other populations may not necessarily reflect environmental and genetic factors for the group of interest. The aim of this study was to develop and validate predictive models for standing height in Mexican adults. For this purpose, 240 male and female adults aged 20 to 59 years, with no apparent spine problems were measured. We measured weight, height and knee length, using an anthropometer of our own design and a glass fiber metric measuring tape. A predictive model for each measuring instrument was developed. Model selection and development of equations were carried out by "all possible regressions and multiple regression" procedures. The predictive models for standing height by the anthropometer and by the measuring tape did not show significant differences between measured and estimated height. The R2 for the two models were 0.93 and 0.92, with a standard error of the estimator (EE) of 2.30 and 2.40 cm, for the anthropometer and the measuring tape, respectively. Both methods were acceptable in terms of concordance, accuracy and precision; however, at very high and low predicted height values, both models showed significant bias, which should be considered when applying these algorithms in different populations. PMID- 26667745 TI - SUBSCAPULAR AND TRICEPS SKINFOLDS REFERENCE VALUES OF HISPANIC AMERICAN CHILDREN AND ADOLESCENTS AND THEIR COMPARISON WITH THE REFERENCE OF CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC). AB - INTRODUCTION: the assessment of the skinfold thickness is an objective measure of adiposity. Therefore, it is a useful tool for nutritional diagnosis and prevention of metabolic risk associated with excess fat in chilhood and adolescence. OBJECTIVE: to provide percentiles of subscapular and triceps skinfolds for Hispanic American schoolchildren and compare them with those published by the Centers for Disease Control and Prevention (CDC) from United States, that it have been commonly used as a reference in most of these countries. METHODS: subscapular and triceps skinfolds were measured in 9.973 schoolchildren 4-19 aged from Spain, Argentina, Cuba, Venezuela and Mexico with Holtain caliper with 0.2 mm accuracy. Percentiles were obtained with the LMS statistical method and were presented in tables divided in stages of 6 months and in curves graphics. The difference between Hispanic American and CDC mean values were provided for P3, P50 and P97 in mm and also were graphically represented. RESULTS: skinfolds measurements obviously increased with age in both sexes but, in boys, this increase is much more marked in highest percentiles between 8 and 13 years; this maximum is reached earlier than what occurs in CDC reference. In both sexes, all percentiles analized in Hispanic American schoolchildren were higher than the CDC reference except P97 up to 10 or 13 years that was notably smaller. CONCLUSIONS: the skinfolds percentiles of Hispanic American children and adolescents differ from CDC that are usually used as reference. The values of subscapular and triceps skinfolds provided in this study, could be applied to populations of a similar ethnic background, especially in comparative studies of body composition. PMID- 26667746 TI - HIGH BODY MASS INDEX AMONG PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION: RESULTS OF A CROSS-SECTIONAL EVALUATION OF NUTRITIONAL STATUS IN A PRIVATE HOSPITAL. AB - BACKGROUND: nutritional status before hematopoietic stem cell transplantation (HSCT) affects prognosis: better nourished patients have shorter time to engraftment, while malnutrition is associated with increase of mortality rates, complications, medical costs, poor quality of life and hospitalization stay. Furthermore, underweight patients have increased risk of death in the early post- HSCT period, and non-relapse mortality is greater for those who are extremely underweight, overweight and obese. Obesity is associated with treatment-related toxicity, higher incidence of grade II-IV acute graft-versus- host disease (GVHD), infections and mortality. The objective of this study was to investigate the nutritional status of patients undergoing HSCT between 2007-2013 in a private hospital, by calculating the body mass index (BMI), to verify the prevalence of any nutritional imbalances, especially obesity. METHODS: in this retrospective study, based on medical records, we analyzed data from all patients with malignant and nonmalignant diseases who underwent HSCT from January 2007 to February 2014 in the Hematology- Oncology and Bone Marrow Transplantation Center at a large, tertiary referral center in Brazil. RESULTS: a total of 257 cases were treated in the period and analyzed, of which 79% were aged up to 65 years old. Among these, 56% were overweight or obese. We observed a higher prevalence of obesity in elderly patients (P < 0.001). The mean BMI of the total sample was 26.4 kg/m2. BMI was significantly different between genders, with higher prevalence of overweight among men (P < 0.001). CONCLUSION: differently from other studies, our investigation has shown low rates of underweight and more overweight and obesity rates in men and elderly patients undergoing HSCT. PMID- 26667747 TI - [CAFFEINE AND QUININE IN SOFT DRINKS; CONTRIBUTION TO THE DIETARY INTAKE]. AB - INTRODUCTION: soft drinks are becoming increasingly consumed by society. They are composed by a great variety of components, some of which can produce adverse effects if they are frequently consumed in high levels. OBJECTIVES: determine caffeine and quinine concentration to prove that those concentration levels are lower than the legal limits allowed and calculate the contribution to dietary intake to obtain the Estimated Daily Intake. METHODS: levels of caffeine and quinine of the main brands of soft drinks were analyzed using High-Performance Liquid Chromatography technique. RESULTS: concentrations were obtained for all brands, and the medium level was estimated. CONCLUSIONS: it has been observed that in any case the maximum concentration limits are exceeded and the contribution to dietary intake doesn't mean adverse reaction. PMID- 26667748 TI - [ASSOCIATION OF SERUM ALBUMIN AND SUBJECTIVE GLOBAL ASSESSMENT ON INCIDENT PERITONEAL DIALYSIS PATIENTS]. AB - INTRODUCTION: serum albumin the biomarker most frequently used as one of three biochemical criteria for diagnosis of protein energy wasting (PEW). However, as a nutritional parameter it's unreliable in chronic kidney disease (CKD). The subjective global assessment (SGA) has been recommended for nutritional evaluation and the PEW in CKD. OBJECTIVE: determine association between the levels of serum albumin and SGA in patients with end stage renal disease (ESRD) who started peritoneal dialysis (PD). METHODS: a cross-sectional study in patients with ESRD were evaluated prior to starting PD. Levels of serum albumin were determined and nutritional assessment was performed by SGA. RESULTS: 69 patients, 46 (67%) men and 23 (33%) women, average age 39.97 +/- 18.30 years old, serum albumin 2.75 +/- 0.65 g/dl, creatinine 18.91 +/- 10.98 mg/dl, urea 314.80 +/- 152.74 mg/dl and BMI 23.37 +/- 3.79 kg/m2, median of GFR 3 (1-12) mL/min/1.73m2. The SGA showed that 34.8% was well nourished, 40.6% had risk of moderate PEW and the 24.6% had severe PEW. There was no association (p = ns) between the levels of serum albumin and SGA. CONCLUSION: the present study shows hypoalbuminemia and PEW are very frequent. The identification of levels of serum albumin and SGA at the beginning of PD in our population could be predictors of mortality. Serum albumin is not a useful tool for nutritional assessment in patients with ERSD who initiate PD. PMID- 26667749 TI - [CONCORDANCE IN THE RESULTS OF CONTROL INTAKE PERFORMANCE OF 72 H BY DIFFERENT HEALTH PROFESSIONALS IN A TERTIARY HOSPITAL]. AB - INTRODUCTION: the nutritional screening CIPA is positive when it fulfills one of the following parameters: Control food Intake (CI) 72 h < 50%; albumin < 3 g/dl; Body Mass Index (BMI) < 18,5 kg/m2 or Mid-Upper Arm Circumference (MUAC) <= 22,5 cm (if BMI cannot be determined). The only parameter no totally objective is the CI so that this study seeks to reinforce its validity. OBJECTIVES: analyze the existing concordance among different health professionals when assessing a CI of 72 h. MATERIALS AND METHOD: retrospective study of patients admitted in hospitalization wards (February-October 2014). Variables considered: age, sex, health service, CI of 72 h and type of diet. The aim of CI is to assess the amount of food consumed, differing between superior or inferior intakes to 50%. It is analyzed the concordance of the results CI determined by a doctor, a nurse and a nutritionist (gold-standard) by the coefficient Kappa (K). Subsequently the sensitivity (S) and specificity (Sp) of positive CI were computed. RESULTS: 176 control of food intake were analyzed. Age 63.70 ?} 14.46 years; 42% women. Units: Digestive (22.2%), Pneumology (42%), Internal Medicine (21.6%), Nephrology (9.1%), others (5.1%). Type of diet: basal (23%), therapeutic (67%), consistency (4%), progressive (3.4%), others (2.3%). It was compared the nursing CI vs. nutritionist (K = 0.798; p < 0.001), and the doctor vs. nutritionist (K = 0.823; p < 0.001). The S and Sp of nursing vs. nutritionist was 84% and 97% while between the doctor and the nutritionist was 84% and 98% respectively. CONCLUSIONS: the concordance of the results of a CI of 72 hours (intakes < or > to 50%) performed in patients hospitalized by a doctor, nurse, and nutritionist is high, minimizing subjectivity to this parameter. The CI is helpful for its use within the routine clinical practice, and particularly within the nutritional screenings, such as CIPA. PMID- 26667750 TI - [VALIDATION OF PREDICTIVE EQUATIONS FOR WEIGHT AND HEIGHT USING BODY CIRCUMFERENCES IN MEXICAN ELDERLYS]. AB - INTRODUCTION: weight and height measurements are important data for the nutritional assessment of elderly people and the implementation of the nutritional care process. Malnutrition is common in this population, who has high rates of disability that difficult to measurement this variables. OBJECTIVE: evaluate the validity of predictive equations for weight and height that include body circumferences created for brazilian population, in mexican elderly people. METHODS: this is a comparative, observational, prospective and cross-sectional study, 61 elderly were evaluated. Body weight, height, half span, calf, arm and abdominal circumferences were determinated. Weight and height were estimated with de predictive equations published by Rabito et al. Bland-Altman analysis and Intraclass Correlation Coefficient were used to assess the levels of agreement between the estimated and the measured values. The level of statistical significance was p < 0.05. RESULTS: the age mean was 78.7 +/- 8.7 and 55.7% were females. The weight mean was 61.9 +/- 14.1 kg, height mean was 155.4 +/- 9.5 cm and Body Mass Index (BMI) mean corresponded to 25.5 +/- 5.1 kg/m. The Bland Altman plots indicated that the 95% confidence interval (95% IC) limits for the difference between real and estimated weight ranged from -14.3 kg to 8.1 kg, the mean of the difference or systematic error (SE) was -3.1 kg, we observed an statistically significant coefficient of 0.12 (p < 0.03). The 95% IC limits for the difference between real and estimated height ranged from -11.1 to 15.9 cm, the diffe rence mean or SE of 2.4 cm, we observed a coefficient of -0.04 (p = 0.67) . Intraclass Correlation Coefficient of 0.72 (p < 0.00) and 0.88 (p < 0.00) were obtained for weight and height, respectively. CONCLUSION: the equations developed by Rabito showed a good agreement when compared with the actual weight and height of elderly people. We observed variations in the estimated weight in obesity elderlys. PMID- 26667751 TI - [SOMATOTYPE JOINT MOBILITY AND RANGES OF HIP AND KNEE OF COLLEGE STUDENTS]. AB - INTRODUCTION: several studies indicate a consistency between the physical inactivity and low levels of mobility in hip and knee joint. OBJECTIVE: to determine the differences in the motion range of the hip and knee joint between the different classifications of somatotype in students of Pedagogy in Physical Education of the Universidad Autonoma de Chile, campus Temuco. METHODS: the sample included 102 physical education students (31.3% female), somatotype was obtained through the protocol of the International Society for the Advancement of Kinanthropometry (ISAK) and the motion range of the hip and knee joint (ROM) using a universal goniometer. RESULTS: the mean somatotype was endo-mesomorphic (4.8 - 3.4 - 2) for the women and meso-endomorphic (3.5 - 5.7 - 2) for the males, while the ROM evaluation indicated that the 50% of the students presented mobility values of joint lower than the normal ones. Furthermore, the endo mesomorphic women showed lower ROM values of medial rotation of the right hip (45.5 degrees +/- 10.2 degrees ; P = 0.0125, t = 2.732) and left hip side rotation (41.7 degrees +/- 10.3 degrees ; P = 0.0256; p = 2.402) than the women meso-endomorphic. CONCLUSION: the results shows a relationship between the somatotype and hip ROM in the women, showing that in the women the most favorable results of joint mobility are related with a greater muscle mass. In contrasts, no significant differences were observed in men. It is important to encourage the development of joint mobility exercises according to the specific needs of each sex. PMID- 26667752 TI - CHANGES IN SOMATOTYPE CHARACTERISTICS IN THE MIDDLE-AGED BULGARIAN MEN. AB - OBJECTIVE: the objective of this cross-sectional research was to outline the different somatotypes and the trends in the changes of the three basic components (endomorphy, mesomorphy and ectomorphy) among the middle-aged Bulgarian men. MATERIAL AND METHODS: the Heath-Carter method was used to identify the anthropometric somatotypes of 860 adult men, aged 30-50 years old, from the city of Plovdiv, located in Central Bulgaria. The men were divided into 4 age groups, in five-year intervals. In each case body height, weight and a series of skinfolds, circumferences and diameters were measured to calculate the somatotype. The SPSS package was used for the statistical analysis. RESULTS: the results show a prominent endo-mesomorphic model in the study sample of male population. We found age-related increase of the values of the musclebone component, retention of the level of the fatty component and a decline in the ectomorphy. Regardless the quantitative changes of the three components, the correlation between them remains constant and the mean somatotype is preserved. A greater variety of morphotypes is found in the group of men aged 30-35. The most homogeneous group is that of the 45-50 year old men. This group is entirely dominated by the mesomorphic component (strength), and the endomorphic component (obesity) is greater than the ectomorphic one (linearity). CONCLUSION: the study finds that in the years between 30 and 50 the men tend to build muscle rather than fat. The 50 year-old men are more mesomorphic than the men at the age of 30, but they are shorter and with less elongated body segments. PMID- 26667754 TI - [COMPARISON OF THE RISKS IN EATING DISORDERS AND BODY IMAGE AMONG MAPUCHES AND NOT MAPUCHES STUDENTS]. AB - INTRODUCTION: there is little evidence about the risks of eating behavior (EBD) and body image disorders (BID) in teen and young ethnic Mapuches population. OBJECTIVE: the purpose of the study was to establish whether there are differences in the risk of EBD and BID in Mapuches and not Mapuches students and associate these variables with the nutritional status. MATERIAL AND METHODS: the sample was composed of 130 adolescents between 14 and 21 years; 95 Mapuches and 35 not Mapuches. In both groups was measured; body mass index (BMI), risks of disorder in the feeding behavior and body image. RESULTS: there were no differences in risks of EBD and ICT to compare by Mapuches ethnic group and not Mapuches (p>0.05). In the comparison by gender women showed higher values (p>0.05) at risk of eating disorders and BID. Students with malnutrition by excess obtained higher scores in the conduct of risk of BID (p=0.000). The risk of BID presented positive association with risk behaviors of EBD (p=0.000 and r=0.536). CONCLUSION: the non-presence of significant differences in the risk of EBD and BID, according to ethnicity, is explained in function of the processes of social and cultural change, where modernization has led to a normalization of cultural patterns associated with eating behavior and body aesthetics between urban, rural and indigenous populations. PMID- 26667753 TI - [NUTRITIONAL STATUS AND BIOCHEMICAL MARKERS OF DEFICIENCY OR EXCESS OF MICRONUTRIENTS IN 4 TO 14 YEAR-OLD CHILEAN CHILDREN: A CRITICAL REVIEW]. AB - The prevalence of obesity in Chilean children has been increasing steadily for the last two decades. The first study to determine nutritional status and food intake in a representative sample of this population was carried out in 1960. Recently the National Food Consumption Survey (ENCA) carried out in 2012 was released by the Ministry of Health. However, this study did not include biochemical determinations of micronutrients which would allow a better diagnosis of nutritional status in children. OBJECTIVE: to review the literature available from 2004 to 2014 in food intake and nutritional status in Chilean children aged 4 to 14 years. METHOD: a total of 362 references published between 2004 and 2014 were obtained through searches in the databases PubMed, Lilacs, Embase and Scielo. From these, 40 articles were selected for a thorough review. RESULTS: food intake by children is characterized by a high-energy intake, a low consumption of fruits and vegetables and a high consumption of bread. The ENCA showed that 95% of the Chilean population has a deficient diet. A high prevalence of obesity is observed from very early in life. There is a dearth of data available on plasma indicators of vitamin and mineral status since 1960, which would provide more reliable information on nutritional assessment. CONCLUSION: It is imperative to implement a representative nutrition survey of children in Chile that includes biochemical indicators to get reliable information in order to develop strategies aimed to correct micronutrient malnutrition from excess or deficiency. PMID- 26667755 TI - ISOLATION AND IDENTIFICATION OF AN ENDOPHYTIC FUNGUS PRODUCING PACLITAXEL FROM TAXUS WALLICHIANA VAR MAIREI. AB - The objective of this study was to isolate endophytic fungi producing paclitaxel from yew for the purpose of paclitaxel manufacture. Surface sterilized bark of Taxus wallichiana var. mairei was used as source material and potato dextrose agar culture medium was used in isolation of endophytic fungi. Fungal cultures were extracted with a mixture of chloroform / methanol (1:1, v/v) and the paclitaxel in the extracts was determined and authenticated with LC-MS. An endophytic fungus that produced paclitaxel was identified by ITS rDNA and 26S D1/D2 rDNA sequencing. The results showed that a total of 435 endophytic fungal strains were isolated from T. wallichiana var. mairei and purified. Only one of these strains produced paclitaxel and it belongs to Fusarium. The paclitaxel productivity in whole PDB culture and that in spent culture medium from this strain is 0.0153 mg/L and 0.0119 mg/L respectively. The paclitaxel content in dry mycelium is 0.27 mg/kg. This isolated endophytic fungus produced paclitaxel at a considerable level and shows potentiality as a producing strain for paclitaxel manufacture after strain improvement. PMID- 26667756 TI - COST-EFFECTIVENESS OF EARLY NUTRITIONAL THERAPY IN MALNOURISHED ADULT PATIENTS IN A HIGH COMPLEXITY HOSPITAL. AB - INTRODUCTION: hospital malnutrition is a frequent worldwide problem and its potential issues related include increased complications, length of stay, mortality, and healthcare costs. OBJECTIVES: the aim of this study was to establish the cost-effectiveness of early nutritional therapy for malnourished patients in a high complexity hospital. MATERIALS AND METHODS: this analytical study with economic assessment included 227 adult hospitalised and malnourished according to the Subjective Global Assessment. The cohort prospective received Early Nutrition Therapy (ENT), whereas the cohort retrospective received Delayed Nutrition Therapy (DNT). The measures of cost-effectiveness included costs by: length of stay, complications and discharge condition. RESULTS: the cohorts were similar in demographic and clinical characteristics, except that the median age, for the ENT was 61 years (interquartile range [IQR]: 48-71) and for the DNT was 55 years (IQR: 44-67) (p = 0.024). The median length of stay was lower in the ENT (11 days, IQR: 7-17) than in the DNT (18 days, IQR: 10-28) (p < 0.001). The cost per patient discharged alive was US $ 10,261.55 in the ENT and US $ 15,553.11 in the DNT (p=0.043); the cost per patient with complications was US $ 13,663.90 in the ENT and US $ 17,860.32 in the DNT (p= 0.058). ENT increased the likelihood of being discharged alive, RR adjusted=0.31; 95% confidence interval (CI): 0.1; 0.6; (p<0.001) and decreased the likelihood of complications RR crude=0.8; 95% CI: 0.6; 0.9; (p=0.006). CONCLUSION: early nutritional therapy for malnourished adult patients appears to be cost-effective because it can reduce the length of stay, complications, mortality and associated costs. PMID- 26667757 TI - [DIETARY HABITS AND FEEDING BELIEFS OF PEOPLE WITH CROHN'S DISEASE]. AB - INTRODUCTION: Crohn's disease (CD) is a chronic illness of unknown etiology. The consequences that CD causes nutritionally depend on several factors. However, little is known about the nutritional practices that CD affected people adopt once diagnosed. OBJECTIVE: to explore the experience of those affected in relation to food intake, with the future goal of understanding those experiences and design effective and appropriate interventions. SUBJECTS AND METHODS: a qualitative design based on ethnographic approach was used. 19 semi-structured interviews were conducted in Alicante, until data saturation was reached and later the analysis of categories and subcategories was developed. RESULTS: 5 categories with their subcategories were identified from the data collected on the experience of feeding: 1) Beliefs about nutrition and CD, 2) Changing eating habits, 3) Finding information about food and CD, 4) The role of professionals, 5) Self-management. CONCLUSIONS: knowledge of the dietary habits of the person with CD, may provide professional workforce with the appropriate information for management and support in terms of prevention, health promotion and health education, useful for the organization of health institutions, where those things are not usually taken into account since the CD approach is purely based on clinical and pathological aspects. Consequently, it appears a need of a new CD perspective based on health, focused on promoting healthy habits and from a multidisciplinary approach. PMID- 26667758 TI - FAT PHOBIA IN MEXICAN NUTRITION STUDENTS. AB - Nutritionists play a major role in the prevention and treatment of obesity. Currently, fat phobia among nutrition students and health workers is resulting in health and social consequences. The aim of this study was to assess the fat phobia among nutrition college students of two schools from different regions in Mexico. Six hundred and thirty 18 to 25 yo nutrition students participated in the study. Fat phobia was assessed using the F-scale, containing 14 pairs of adjectives that described people with obesity. Participants achieved a mean F scale score of 3.45, which could be considered a moderate amount of fat phobia. Only twelve per cent showed neutral or positive attitudes towards obesity (<= 2.5), while negative attitude (>= 2.5) was observed among 88% of all students showing a high prevalence of fat phobia towards obesity. PMID- 26667759 TI - [SHORT BOWEL SYNDROME AND NUTRITIONAL ENTERAL]. AB - The particularity of this case is the nutritional management that has managed to avoid the use of prolonged parenteral nutrition and possible complications by placing jejunal tube at the distal end in patients with short bowel. It is a 34 year-old colecistectomizado complicated with postoperative peritonitis and dehiscence; two years he studied with small bowel obstruction, he was made de volvulus and was complicated with two leak at different times after the second escape took place jejunostomy side double barreled shotgun level dehiscence, presented high debits by afferent loop of the terminal jejunostomy; during admission, polyurethane probe enteral feeding was inserted by the efferent loop jejunostomy. He received jejunal tube feeding laundry in the efferent loop terminal with decreased weight gain and subsequent reconstruction of intestinal transit debit proximal jejunostomy. PMID- 26667760 TI - [EVIDENCE 1 A WITH RECOMMENDATION A?, OR 1 ++ WITH RECOMMENDATION B? WHAT REALLY UNDERSTAND ABOUT THE LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION? PART II]. PMID- 26667761 TI - [EVIDENCE 1 A WITH RECOMMENDATION A?, OR 1 ++ WITH RECOMMENDATION B? WHAT REALLY UNDERSTAND ABOUT THE LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION? PART III]. PMID- 26667762 TI - [SOPORTE NUTRICIONAL ESPECIALIZADO]. PMID- 26667763 TI - [AGRESION, SISTEMA INMUNE Y FARMACONUTRICION]. PMID- 26667764 TI - [MANUAL DE PATOLOGIA NUTRICIONAL DEL ADULTO PARA DIETISTAS-NUTRICIONISTAS]. PMID- 26667766 TI - Endonuclease G depletion may improve efficiency of first generation adenovirus vector DNA replication in HeLa cells. AB - First generation adenovirus (Ad5 DeltaE1,E3) vectors are able to replicate their DNA in many tumour cells and can be used for oncotherapy. Highest rates of viral DNA replication occur in the G2/M transition of the cell cycle. In this study, we tried to increase the efficiency of Ad5 DeltaE1,E3 DNA replication in the cervical carcinoma HeLa cells by using RNA interference (RNAi) to target endonuclease G (EndoG) whose depletion leads to an accumulation of cells in the G2/M transition. Targeting of EndoG by an shRNA encoded on an Ad5 DeltaE1,E3 vector resulted in an early proliferation defect of cervical carcinoma HeLa cells. This effect coincided with enhanced DNA replication and encoded transgene expression of an Ad5 DeltaE1,E3 vector. Applied in high concentrations, the EndoG targeting Ad5 DeltaE1,E3 vector showed enhanced HeLa cell killing ability relative to control Ad5 DeltaE1,E3 vectors. These effects are most likely the result of EndoG depletion, which causes cells to accumulate in the G2/M transition of the cell cycle and extends favourable cellular conditions for Ad5 DeltaE1,E3 DNA replication. Targeting of EndoG by RNAi may be a viable strategy for improving both the levels of transgene expression and the oncolytic properties of first generation adenovirus vectors. PMID- 26667767 TI - Trans-resveratrol induces a potential anti-lipogenic effect in lipopolysaccharide stimulated enterocytes. AB - A DNA microarray analysis was conducted in Caco-2 cells to analyse the protective effects of trans-resveratrol on enterocyte physiology and metabolism in pro inflammatory conditions. Cells were pre-treated with 50 MUMU of trans-resveratrol and, subsequently, lipopolysaccharide (LPS) was added for 48 h. The microarray analysis revealed 121 genes differentially expressed between resveratrol-treated and non-treated cells (B> 0, is the odd thatthe gene is differentially expressed). Inhibitor of DNA binding 1 (ID1), histidine-rich glycoprotein (HRG), NADPH oxidase (NOX1) and sprouty homolog 1 (SPRY), were upregulated by LPS treatment, but significantly blocked by trans-resveratrol pre-treatment (padj< 0.05, after adjusting for Benjamini-Hocheberg procedure). Moreover, genes implicated in synthesis of lipids (z-score= -1.195) and concentration of cholesterol (z-score= -0.109), were markedly downregulated by trans-resveratrol. Other genes involved in fat turnover, but also in cell death and survival function, such as transcription factors Kruppel-like factor 5 (KLF5) and amphiregulin (AREG), were also significantly inhibited by trans-resveratrol pre treatment. RT-qPCR-data confirmed the microarray results. Special mention deserves acyl-CoA synthetase long-chain family member 3 (ACSL3) and endothelial lipase (LIPG), which were downregulated by this stilbene and have been previously associated with fatty acid synthesis and obesity in other tissues. This study envisages that trans-resveratrol might exert an important anti-lipogenic effect at intestinal level under pro-inflammatory conditions, which has not been previously described. PMID- 26667768 TI - CD45RO+ memory T-cells produce IL-17 in patients with atherosclerosis. AB - Several CD4+ T helper (Th) cell subsets are shown to play a role in atherosclerotic lesion formation and progression. We investigated the frequencies of IL-17 and IFN-gamma producing CD4+ T-cell subsets in the peripheral blood mononuclear cells (PBMCs) of 10 patients with atherosclerosis and 6 individuals with normal/insignificant coronary artery disease. Th1 and Th17 memory and effector T-cells were enumerated by flowcytometry and correlated with the clinical data and lipid profiles of the subjects. We found the ex-vivo (P=0.0001) and in-vitro production of IL-17 (P=0.001) but not IFN-gamma by CD4+ memory T cells of patients. CD45RO+ memory cells were the major producers of IL-17 and the CD4+CD45RO+PD-1- T-cells of the patients produced higher levels of IFN-gamma than controls (P=0.02). Positive correlations between the frequency of CD4+CD45RO+IL 17+IFN-gamma- T-cells and serum LDL-C (P=0.007), triglyceride (P=0.02), and systolic (P=0.001) and diastolic (P=0.009) blood pressures (BP) were found. The frequency of CD4+CD45RO+IL-17-IFN-gamma- T-cells, which was higher in controls than patients, showed negative correlations with the serum LDL-C (P=0.01) and triglyceride (P=0.02) levels and systolic (P=0.003) and diastolic (P=0.01) BPs. The ex-vivo Th17 deviation of memory T-cells in atherosclerosis and high PD-1 expression are associated with the correlates of atherogenesis such as LDL, TG, and BP. PMID- 26667769 TI - Association between a Functional HLA-G 14-bp Insertion/deletion Polymorphism and Susceptibility to Autoimmune Diseases: A Meta-analysis. AB - The aim of this study was to determine whether a functional human leukocyte antigen-G (HLA-G) 14-bp insertion (I)/deletion (D) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted to assess the association between an HLA-G 14-bp I/D polymorphism and autoimmune diseases using 1) allele contrast, as well as 2) recessive, 3) dominant, and 4) codominant models. Sixteen articles that included 20 comparative studies with 3,555 patients and 5,225 controls were included in the meta-analysis. These studies were performed on nine Caucasian, six South American, three Asian, one Arab, and one African population samples. Our meta-analysis revealed no association between autoimmune diseases and the HLA-G 14-bp I/D polymorphism [odds ratio (OR) for allele I = 1.055; 95% confidence interval (CI) = 0.963 1.156; p = 0.251)]. However, meta-analysis according to autoimmune disease type revealed an association between systemic lupus erythematosus (SLE) and the II+ID genotype of the HLA-G 14-bp I/D polymorphism (OR = 1.205; 95% CI = 1.036-1.403; p = 0.016). Furthermore, analysis using a codominant model revealed an association between this polymorphism and SLE (OR for ID vs. DD = 1.203; 95% CI = 1.024 1.413; p = 0.024). In contrast, our meta-analysis revealed no association between rheumatoid arthritis (RA), multiple sclerosis (MS), or Crohn's disease (CD) and the HLA-G 14-bp I/D polymorphism. This meta-analysis showed that the HLA-G 14-bp I/D polymorphism is associated with susceptibility to a subgroup of autoimmune diseases such as SLE, but not RA, MS, or CD. These results support the existence of an association between the HLA-G gene and a subgroup of autoimmune diseases. PMID- 26667770 TI - Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway. AB - Genotoxic stress activates checkpoint signaling pathways that activate the checkpoint kinases ATM and ATR, halt cell cycle progression, and promote DNA repair. A number of proteins act in concert with ATR to phosphorylate Chk1, including RAD17, the RAD9-RAD1-HUS1 complex, ATR/ATRIP and TopBp1. However, how these proteins involved act in concert with one another to propagate and maintain the checkpoint response is not well understood. Here, we reported that upregulation of RAD9 protein increased the quantity of ATRIP, suggesting that RAD9 activation will induce more efficient accumulation of ATRIP in vivo. Furthermore, the DNA damage-induced ATRIP foci formation was faster in the mRad9 /- ES cells. Also, ATRIP interacts specifically with RAD9, but not HUS1 and RAD1. Taken together, we suggested that RAD9 could affect both the ATRIP protein levels and DNA damage-induced ATRIP foci formation. Thus, we propose a role of RAD9 in the ATR-Chk1 pathway that is necessary for successful formation of the damage sensing complex and DNA damage checkpoint signaling. PMID- 26667771 TI - Role of Berberine on molecular markers involved in migration of esophageal cancer cells. AB - Berberine is an isoquinoline alkaloid found in several plant species like famous chinese herb, Rhizoma coptidis which has been used locally as a strong gastrointestinal remedy for thousands of years. The inhibitory effects of berberine on tumor progression properties have been reported before. In this study, we investigated the effect of berberine on an esophageal cancer cell line, KYSE-30 with emphasis on its effects on the expression of certain chemokine receptors. The cytotoxic effect of berberine on KYSE-30 cells was analyzed by MTT assay. In vitro cell migration assay was also applied to the treated cells and the expression levels of the selected chemokine receptors (CXCR4 and CCR7) was measured at mRNA level. A retarded growth, associated with increasing concentrations of berberine, was obvious. On the other hand, the migration rate of the cells was decreased when they were treated with different concentrations of berberine and the expression levels of the two chemokine receptors, involved in the migration and metastasis of esophageal cancer cells, were decreased following the same treatments. With these results, we tend to conclude that berberine might be a proper candidate for further investigations, by targeting the chemokine receptors, and possible applications as anti-metastatic agent in cancer studies. PMID- 26667772 TI - Inferring chronological age from DNA methylation patterns of human teeth. AB - OBJECTIVE: Current methods to determine chronological age from modern and ancient remains rely on both morphological and molecular approaches. However, low accuracy and the lack of standardized protocols make the development of alternative methods for the estimation of individual's age even more urgent for several research fields, such as biological anthropology, biodemography, forensics, evolutionary genetics, and ancient DNA studies. Therefore, the aim of this study is to identify genomic regions whose DNA methylation level correlates with age in modern teeth. METHODS: We used MALDI-TOF mass spectrometry to analyze DNA methylation levels of specific CpGs located in the ELOVL2, FHL2, and PENK genes. We considered methylation data from cementum, dentin and pulp of 21 modern teeth (from 17 to 77 years old) to construct a mathematical model able to exploit DNA methylation values to predict age of the individuals. RESULTS: The median difference between the real age and that estimated using DNA methylation values is 1.20 years (SD = 1.9) if DNA is recovered from both cementum and pulp of the same modern teeth, 2.25 years (SD = 2.5) if DNA is recovered from dental pulp, 2.45 years (SD = 3.3) if DNA is extracted from cementum and 7.07 years (SD = 7.0) when DNA is recovered from dentin only. DISCUSSION: We propose for the first time the evaluation of DNA methylation at ELOVL2, FHL2, and PENK genes as a powerful tool to predict age in modern teeth for anthropological applications. Future studies are needed to apply this method also to historical and relatively ancient human teeth. PMID- 26667773 TI - Comparison of antiproliferative and apoptotic effects of a novel proteasome inhibitor MLN2238 with bortezomib on K562 chronic myeloid leukemia cells. AB - Inhibition of the proteasome has emerged as a clinically effective anticancer therapeutic approach in recent years. Bortezomib (Velcade(r)) showed extremely high potency against a wide range of cancer cell lines. Ixazomib (MLN9708 MLN2238), the second-generation proteasome inhibitor, selectivity and potency were similar to that of bortezomib, is currently being investigated in phase I studies. It shows superior antitumor activity in hematologic malignancy, especially multiple myelomas. In this study, for the first time, we evaluated and compared the antiproliferative and apoptotic effects of the novel proteasome inhibitor MLN2238 (the active form of MLN9708) with bortezomib using in vitro chronic myeloid leukemia. Cytotoxic and apoptotic effects of MLN2238 and bortezomib were determined by trypan blue dye exclusion assays, WST-1 cell proliferation assay, increased AnnexinV-PI binding capacity, changes in caspase-3 activity and loss of mitochondrial membrane potential (JC-1). Associated with proteasome pathway NFkappaB1 and c-myc mRNA expression levels were examined by the qRT-PCR method. We observed that cytotoxic and apoptotic effects on K562 cells were started at 5 MUm of MLN2238 and 1 MUm of bortezomib after 24 and 48 h. Also, MLN2238 and bortezomib downregulated NFkappaB1 and c-myc mRNA expression at 24 h. Our result revealed that MLN22238 and bortezomib had significant cytotoxic and apoptotic effects on K562 cells. Here, we first demonstrate in vitro data that support the development of MLN2238, by direct comparison with bortezomib on K562 cells. PMID- 26667775 TI - Two new indole alkaloids from Hunteria zeylanica. AB - Two new indole alkaloids, 14beta-hydroperoxy-eburnamine (1) and 18alpha-hydroxy eburnamine (2), together with three known indole alkaloids, (-)-eburnamonine (3), (-)-eburnamenine (4), and eburnamine (5) were isolated from Hunteria zeylanica collected in Hainan Province of China. Their structures were determined by spectroscopic analysis. The relative configuration of 2 was deduced by NOE experiment and evidenced by the calculations for energy minimization with the molecular modeling program Chem3D Ultra 10.0. PMID- 26667774 TI - Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children. AB - Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and beta-Crosslaps (beta CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and beta-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in beta-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the beta-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and beta-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker beta-CTx was observed. PMID- 26667776 TI - Preparation of uniform Si nanoparticles for high-performance Li-ion battery anodes. AB - Nanostructured silicon has attracted a great deal of attention as an excellent anode material for Li ion batteries (LIBs). However, the use of Si nanomaterials in LIBs is severely hindered by their preparative methods owing to the high cost, low yield, and harsh synthetic conditions. Herein, we report a new method for the synthesis of uniform Si nanocrystals based on the magnesiothermic reduction of natural attapulgite clay. The obtained Si nanocrystals with a uniform size of ca. 10 nm are coated with polypyrrole (denoted ppy@Si) and show excellent electrochemical performance as anode materials for LIBs. After charging discharging for 200 cycles at a current density of 0.6 A g(-1), the specific capacity value of the ppy@Si anode is ~954 mA h g(-1). Because of the abundance of attapulgite, the obtained silicon nanoparticles can be exploited as a practical anode material for high-performance Li-ion batteries. PMID- 26667777 TI - Multianalyte Conventional Reference Material (MacRM): A Useful Tool for Nationwide Standardization of Laboratory Measurements for Medical Care-A Model Study in Japan. AB - BACKGROUND: The Japanese Committee for Clinical Laboratory Standards (JCCLS) has developed a multianalyte conventional reference material (MacRM) for nationwide standardization of laboratory measurements. METHODS: To prepare the MacRM, pooled sera were obtained from healthy Japanese individuals. Target values of the pooled sera for 30 analytes were assigned on the basis of the measurement results of 45 certified clinical laboratories whose calibration was verified by measuring certified reference materials (CRMs) provided by the National Institute of Standards and Technology, the Institute for Reference Materials and Measurements, and JCCLS. Commutability of MacRM was assessed by comparison with results for 150 individual inpatients at Fukuoka University Chikushi Hospital. Survey samples were prepared by essentially the same method for MacRM but without target values. The survey samples were used to assess agreement among 165 laboratories that used various assay kits and platforms calibrated with the MacRM. RESULTS: The commutability of MacRM was confirmed for 30 analytes with sera from 150 individual patients. The imprecision (CV) of measurements of survey samples (high and low concentrations) among the 165 laboratories was 0.4%-10.0%. Twenty-six of 30 analytes were within the goals for interinstitutional allowable bias. An aliquot of MacRM stored frozen at -80 degrees C remained stable for >=4 years. CONCLUSIONS: The MacRM was successfully applied as a calibrator to achieve nationwide standardization for 30 analytes measured by 165 laboratories that used various methods from different manufacturers. PMID- 26667780 TI - Global patterns and predictors of stem CO2 efflux in forest ecosystems. AB - Stem CO2 efflux (ES) plays an important role in the carbon balance of forest ecosystems. However, its primary controls at the global scale are poorly understood and observation-based global estimates are lacking. We synthesized data from 121 published studies across global forest ecosystems and examined the relationships between annual ES and biotic and abiotic factors at individual, biome, and global scales, and developed a global gridded estimate of annual ES . We tested the following hypotheses: (1) Leaf area index (LAI) will be highly correlated with annual ES at biome and global scales; (2) there will be parallel patterns in stem and root CO2 effluxes (RA) in all forests; (3) annual ES will decline with forest age; and (4) LAI coupled with mean annual temperature (MAT) and mean annual precipitation (MAP) will be sufficient to predict annual ES across forests in different regions. Positive linear relationships were found between ES and LAI, as well as gross primary production (GPP), net primary production (NPP), wood NPP, soil CO2 efflux (RS), and RA . Annual ES was correlated with RA in temperate forests after controlling for GPP and MAT, suggesting other additional factors contributed to the relationship. Annual ES tended to decrease with stand age. Leaf area index, MAT and MAP, predicted 74% of variation in ES at global scales. Our statistical model estimated a global annual ES of 6.7 +/- 1.1 Pg C yr(-1) over the period of 2000-2012 with little interannual variability. Modeled mean annual ES was 71 +/- 43, 270 +/- 103, and 420 +/- 134 g C m(2) yr(-1) for boreal, temperate, and tropical forests, respectively. We recommend that future studies report ES at a standardized constant temperature, incorporate more manipulative treatments, such as fertilization and drought, and whenever possible, simultaneously measure both aboveground and belowground CO2 fluxes. PMID- 26667778 TI - Basal body multipotency and axonemal remodelling are two pathways to a 9+0 flagellum. AB - Eukaryotic cilia/flagella exhibit two characteristic ultrastructures reflecting two main functions; a 9+2 axoneme for motility and a 9+0 axoneme for sensation and signalling. Whether, and if so how, they interconvert is unclear. Here we analyse flagellum length, structure and molecular composition changes in the unicellular eukaryotic parasite Leishmania during the transformation of a life cycle stage with a 9+2 axoneme (the promastigote) to one with a 9+0 axoneme (the amastigote). We show 9+0 axonemes can be generated by two pathways: by de novo formation and by restructuring of existing 9+2 axonemes associated with decreased intraflagellar transport. Furthermore, pro-basal bodies formed under conditions conducive for 9+2 axoneme formation can form a 9+0 axoneme de novo. We conclude that pro-centrioles/pro-basal bodies are multipotent and not committed to form either a 9+2 or 9+0 axoneme. In an alternative pathway structures can also be removed from existing 9+2 axonemes to convert them to 9+0. PMID- 26667781 TI - Immunopathology in Taenia solium neurocysticercosis. AB - Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented. PMID- 26667782 TI - Letter to the editor regarding: Management of invasive well-differentiated thyroid cancer: An American Head and Neck Society Consensus Statement. PMID- 26667784 TI - Induction of memory cytotoxic T cells to influenza A virus and subsequent viral clearance is not modulated by PB1-F2-dependent inflammasome activation. AB - Expression of the viral virulence protein PB1-F2 during infection has been linked to NLRP3 inflammasome complex activation in macrophages and induction of early inflammatory events enhancing immunopathology during influenza disease. We sought to determine whether PB1-F2-specific NLRP3 inflammasome activation influenced the magnitude and/or robustness of the CD8(+) T-cell responses specific for conserved viral antigens and subsequent virus elimination. Using murine heterosubtypic viral infection models, we showed that mice infected with virus unable to produce PB1-F2 protein showed no deficit in the overall magnitude and functional memory responses of CD8(+) T cells established during the effector phase compared with those infected with wild-type PB1-F2-expressing virus and were equally capable of mounting robust recall responses. These data indicate that while expression of PB1-F2 protein can induce inflammatory events, the capacity to generate memory CD8(+) T cells specific for immunodominant viral epitopes remains uncompromised. PMID- 26667785 TI - Surgical treatment of scapulohumeral subluxation in an alpaca (Vicugna pacos) using osteotomy of the acromion, open reduction and extracapsular tension sutures. AB - CASE HISTORY AND CLINICAL FINDINGS: A 3.3-year-old male alpaca, weighing 60 kg was referred for investigation of a severe left forelimb lameness of 4 weeks duration. A scapulohumeral subluxation had been diagnosed radiographically by the referring veterinarian. CLINICAL FINDINGS AND DIAGNOSIS: Based on clinical, ultrasonographic and radiographic findings the diagnosis of cranio-lateral subluxation of the left humeral head was confirmed. In addition, a full thickness lesion (approximately 1*1 cm) of the articular cartilage on the caudomedial aspect of the humeral head was diagnosed by arthroscopy. TREATMENT AND OUTCOME: Treatment included open reduction with internal fixation. Severe muscle contraction and local tissue fibrosis around the scapulohumeral joint (SHJ) required osteotomy of the acromion 3 cm proximal to the distal acromial edge, to allow adequate access. Internal stabilisation was achieved by placing tension band sutures between one cortical screw in the scapular neck and two cortical screws, with washers, craniolaterally on the greater tubercle of the humerus. Post-surgery, a carpal flexion sling was applied with the carpus maintained in 70 degrees flexion for 4 weeks to avoid postoperative weight-bearing. An exercise programme was started 8 days after surgery and continued for 12 weeks. The alpaca had an uneventful postsurgical recovery and showed no lameness after 8 weeks. The long-term outcome was excellent; 21 months after surgery the alpaca was sound and the range of movement of the left SHJ was equal to the right SHJ. CLINICAL RELEVANCE: Even in this chronic case of subluxation of the SHJ of 4 weeks duration, surgical treatment using osteotomy of the acromion, open reduction and internal fixation with extracapsular scapulohumeral tension sutures resulted in an excellent long-term outcome in this alpaca, despite the presence of a cartilage lesion. PMID- 26667783 TI - Common errors in mass spectrometry-based analysis of post-translational modifications. AB - Mass spectrometry (MS) is a powerful tool to analyze complex mixtures of proteins in a high-throughput fashion. Proteome analysis has already become a routine task in biomedical research with the emergence of proteomics core facilities in most research institutions. Post-translational modifications (PTMs) represent a mechanism by which complex biological processes are orchestrated dynamically at the systems level. MS is rapidly becoming popular to discover new modifications and novel sites of known PTMs, revolutionizing the current understanding of diverse signaling pathways and biological processes. However, MS-based analysis of PTMs has its own caveats and pitfalls that can lead to erroneous conclusions. Here, we review the most common errors in MS-based PTM analyses with the goal of adopting strategies that maximize correct interpretation in the context of biological questions that are being addressed. Finally, we provide suggestions that should help mass spectrometrists, bioinformaticians and biologists to perform and interpret MS-based PTM analyses more accurately. PMID- 26667786 TI - The effects of thematic relations on picture naming abilities across the lifespan. AB - A picture-word interference paradigm tracked patterns of activation during picture naming in 87 individuals (age range 17-80 years old). Distractor words were presented at stimulus onset asynchronies (SOAs) of -200, -100, and 0 ms bearing a has a-, location, or no relationship to the picture. Analyses of group naming reaction times revealed significant facilitation effects for both semantic relation types for all age groups. Analyses of temporal patterns of activation revealed significant effects primarily at SOAs of -200 and -100 ms. These findings provide evidence that both thematic relations are particularly salient in how semantic knowledge is organized, and that the patterns of effects from these semantic relations remain the same as one ages. PMID- 26667787 TI - Validation of two independent photogrammetric techniques for determining body measurements of gorillas. AB - The ability to accurately measure morphological characteristics of wild primates in the field is challenging, yet critical for understanding fundamental aspects of their biology and behavior. Recent studies have shown that digital photogrammetry can be used to non-invasively measure morphological traits of wild primates, as it allows for the determination of geometric properties of objects remotely from photographic images. We report here on a rare opportunity to test this methodology by comparing measurements obtained directly from living great apes to those obtained from photographs. We test the accuracy and precision of two independent photogrammetric techniques, employing the use of parallel lasers and a distance meter, respectively, for obtaining measurements of static objects and captive western lowland gorillas (Gorilla gorilla gorilla) (n = 4) at Zoo Atlanta. For static objects, the mean percent error between corresponding measurements collected by the same observer directly versus using photogrammetry was 0.49-0.74% for the parallel laser method and 0.62-0.76% for the distance meter method. For gorillas, mean percent error between corresponding direct and remote measurements was 2.72-5.20% for the parallel laser method and 2.20-7.51% for the distance meter method. Correlations between direct measurements and corresponding parallel laser and distance meter measurements of gorillas were highly significant with R2 values and slopes approaching 1.0 (parallel lasers: R2 = 0.9989, P < 0.0001; distance-meter: R2 = 0.9990, P < 0.0001). Further, variation between measurements of the same targets collected repeatedly by the same observer, and between different observers, was uniformly low across methods (CV, range = 0.003-0.013). While errors are slightly higher for the distance meter technique, both methods show great promise for addressing a wide range of questions requiring the non-invasive collection of morphological data from wild primates. Am. J. Primatol. 78:418-431, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26667788 TI - FGFR1 and KAT6A rearrangements in patients with hematological malignancies and chromosome 8p11 abnormalities: biological and clinical features. PMID- 26667790 TI - Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus. AB - Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID- 26667791 TI - Integrating electronic health record genotype and phenotype datasets to transform patient care. AB - The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 mandates the development and implementation of electronic health record (EHR) systems across the country. While a primary goal is to improve the care of individual patients, EHRs are also key enabling resources for a vision of individualized (or personalized or precision) medicine: the aggregation of multiple EHRs within or across healthcare systems should allow discovery of patient subsets that have unusual and definable clinical trajectories that deviate importantly from the expected response in a "typical" patient. The spectrum of such personalized care can then extend from prevention to choice of medication to intensity or nature of follow-up. PMID- 26667792 TI - Hyaluronic Acid Assays: Turbidimetric or Enzyme-Based Immune Assay? A Method Comparison Study. AB - BACKGROUD: Hyaluronic acid (HA) is proposed as a marker of functional liver capacity. The aim of the present study was to compare a new turbidimetric assay for measuring HA with the current standard method. METHODS: HA was measured by a particle-enhanced turbidimetric immunoassay (PETIA) and enzyme-linked immunosorbent assay (ELISA) in a 40-sample dilution series and 39 intensive care unit (ICU) patients. Agreement was assessed with Bland-Altman's method. RESULTS: In the ICU patients, the median HA concentration was 159.0 ng/ml (interquartile range (IQR) 117.5-362.5 ng/ml) with ELISA and 157.5 ng/ml (IQR 92.5-359.6 ng/ml) with PETIA. The mean difference was 12.88 ng/ml (95% CI, -4.3 to 30.1 ng/ml, P = 0.14) and the 95% limits of agreement were -91.17 to 116.9 ng/ml. In the dilution series, the mean difference was -59.26 ng/ml (95% CI, -74.68 to 43.84 ng/ml, P < 0.0001) and the 95% limits of agreement were 35.23 to -153.8 ng/ml. CONCLUSION: We found random variation between the PETIA and ELISA test that could affect performance in a clinical context, but only to a lesser extent in a research context. The new clinical biochemistry assay for HA determination will allow for large studies of the clinical utility of HA. PMID- 26667793 TI - HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma. AB - The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed. PMID- 26667795 TI - Acid-sensing ion channel (ASIC) 4 predominantly localizes to an early endosome related organelle upon heterologous expression. AB - Acid-sensing ion channels (ASICs) are voltage-independent proton-gated amiloride sensitive sodium channels, belonging to the DEG/ENaC gene family. Six different ASICs have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4) that are activated by a drop in extracellular pH, either as homo- or heteromers. An exception is ASIC4, which is not activated by protons as a homomer and which does not contribute to functional heteromeric ASICs. Insensitivity of ASIC4 to protons and its comparatively low sequence identity to other ASICs (45%) raises the question whether ASIC4 may have different functions than other ASICs. In this study, we therefore investigated the subcellular localization of ASIC4 in heterologous cell lines, which revealed a surprising accumulation of the channel in early endosome-related vacuoles. Moreover, we identified an unique amino terminal motif as important for forward-trafficking from the ER/Golgi to the early endosome-related compartment. Collectively, our results show that heterologously expressed ASIC4 predominantly resides in an intracellular endosomal compartment. PMID- 26667794 TI - Evaluation of depression and anxiety in empty nose syndrome after surgical treatment. AB - OBJECTIVES/HYPOTHESIS: Empty nose syndrome (ENS) is often associated with psychological symptoms. With the absence of psychiatric instruments utilized in the current literature, the assessment of psychological disorder is limited, and the effectiveness of surgical intervention in improving such disorders in ENS are not well understood. The aim of this study was to evaluate the change in depression and anxiety before and after surgical treatment for ENS STUDY DESIGN: Prospective cohort study in a tertiary medical center. METHODS: ENS patients indicated for surgical treatment were enrolled. The Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI) questionnaires were completed by these patients before and after surgery to assess the level of depression and anxiety. RESULTS: A total of 20 patients completed the BDI-II and BAI before and after surgical treatment. A majority of patients developed depression and anxiety prior to surgical treatment. The severity of depression and anxiety were significantly decreased following the surgery; the mean scores of both the BDI-II and BAI improved from moderate severity to normal (both P < .001). The preoperative total score was found to be a powerful predictor for the postoperative improvement in both BDI-II and BAI (P < .001). Female patients had significantly worse preoperative scores (P = .005) and greater postoperative improvement (P = .012) in the BDI-II. CONCLUSIONS: Depression and anxiety are psychological disorders prevalent among ENS patients. Surgical treatment for ENS is effective in improving depression and anxiety. Patients with worse preoperative BDI-II and BAI scores as well as female patients may be better candidates for surgical intervention. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1284-1289, 2016. PMID- 26667796 TI - Upper arm venous compliance and fitness in stable coronary artery disease patients and healthy controls. AB - OBJECTIVES: Arteries have been examined extensively in coronary artery disease (CAD), while less attention has been paid to veins. AIMS: (1) To determine whether venous compliance or venous outflow in the upper arm is reduced in CAD patients compared to healthy age- and fitness-matched controls; and (2) to examine the association between upper arm venous compliance and total blood volume. DESIGN: Fifteen patients with stable CAD (age 62.1 +/- 5.7 years, body mass index 26.5 +/- 3.2 kg.m2 , fat-free mass 59.3 +/- 7.6 kg, mean arterial pressure 98.9 +/- 8.0 mmHg, VO2peak : 2.92 +/- 0.53 l min-1 ) were compared to twelve healthy age- and fitness-matched controls (age 62.2 +/- 3.7 years, body mass index 26.2 +/- 2.3 kg m2 , fat-free mass 61.0 +/- 9.2 kg, mean arterial pressure 96.5 +/- 9.1 mmHg, VO2peak : 3.24 +/- 0.48 l min-1 ). Venous compliance was examined using high-resolution ultrasound and Doppler in the basilic vein. Blood volumes were measured by the optimized CO rebreathing method. RESULTS: Equal upper arm venous compliance normalized to blood volume (patients: 0.28 +/- 0.26 mm3 mmHg-1 l-1 , healthy controls: 0.16 +/- 0.11 mm3 mmHg-1 l-1 ) and peak venous outflow normalized to blood volume (patients: 10.4 +/- 3.9 cm s-1 l 1 , healthy controls: 8.3 +/- 0.8 cm s-1 l-1 ) were found in patients with CAD and healthy age- and fitness-matched controls. Additionally, no difference was found in blood volume (patients: 6.06 +/- 0.79 l, healthy controls: 6.68 +/- 1.27 l) or VO2peak . CONCLUSION: Comparable upper arm venous compliance and venous outflow in CAD patients and healthy age- and fitness-matched controls might indicate that high VO2peak and blood volume could prevent possible disease induced reductions in venous compliance in CAD. PMID- 26667798 TI - Harmonization in laboratory medicine: Requests, samples, measurements and reports. AB - In laboratory medicine, the terms "standardization" and "harmonization" are frequently used interchangeably as the final goal is the same: the equivalence of measurement results among different routine measurement procedures over time and space according to defined analytical and clinical quality specifications. However, the terms define two distinct, albeit closely linked, concepts based on traceability principles. The word "standardization" is used when results for a measurement are equivalent and traceable to the International System of Units (SI) through a high-order primary reference material and/or a reference measurement procedure (RMP). "Harmonization" is generally used when results are equivalent, but neither a high-order primary reference material nor a reference measurement procedure is available. Harmonization is a fundamental aspect of quality in laboratory medicine as its ultimate goal is to improve patient outcomes through the provision of accurate and actionable laboratory information. Patients, clinicians and other healthcare professionals assume that clinical laboratory tests performed by different laboratories at different times on the same sample and specimen can be compared, and that results can be reliably and consistently interpreted. Unfortunately, this is not necessarily the case, because many laboratory test results are still highly variable and poorly standardized and harmonized. Although the initial focus was mainly on harmonizing and standardizing analytical processes and methods, the scope of harmonization now also includes all other aspects of the total testing process (TTP), such as terminology and units, report formats, reference intervals and decision limits as well as tests and test profiles, requests and criteria for interpretation. Several projects and initiatives aiming to improve standardization and harmonization in the testing process are now underway. Laboratory professionals should therefore step up their efforts to provide interchangeable and comparable laboratory information in order to ultimately assure better diagnosis and treatment in patient care. PMID- 26667799 TI - Progress in Primary Aldosteronism: Translation on the Move. AB - Hypertension is a major cardiovascular risk factor that affects between 10-40% of the general population in an age dependent manner. The renin-angiotensin aldosterone system (RAAS) regulates blood pressure, fluid volume, and the vascular response to injury and inflammation 1. Chronic RAAS activation in the presence of sufficient sodium consumption leads to persistent hypertension, setting off a cascade of inflammatory, thrombotic, and atherogenic effects eventually leading to end-organ damage 2 3. Accordingly, numerous studies have demonstrated that elevated renin and/or aldosterone levels are predictors of adverse outcome in hypertension 4, heart failure 5 6, myocardial infarction 7, and renal insufficiency 8 and influence insulin resistance 9. Primary aldosteronism (PA) is the most common secondary form of hypertension with an estimated prevalence between 4 and 12% of hypertensives 10 11 12 and 11-20% in patients that are resistant to combined antihypertensive medication 13 14. Given the severe cardiovascular adverse effects of aldosterone excess that are independent of high blood pressure levels 15 16 17 18 detection and treatment of PA has important impact on clinical outcome and survival. PMID- 26667800 TI - Steroid Hormone Production in Patients with Aldosterone Producing Adenomas. AB - Primary aldosteronism encompasses 2 major underlying causes: (1) aldosterone producing adenoma and (2) bilateral adrenal hyperplasia. In addition to the aldosterone excess, increased production of other compounds of the steroidogenic pathways may be involved. Until recently, most studies examined the production of steroids other than aldosterone in tumor tissue, urine, or peripheral plasma samples, but several new studies have also addressed steroid levels in adrenal venous blood samples using liquid chromatography tandem mass spectrometry. Plasma and tissue levels of several precursors of aldosterone with mineralocorticoid activity are higher in patients with aldosterone producing adenomas than in those with bilateral hyperplasia. These include corticosterone, deoxycorticosterone, and their 18-hydroxylated metabolites. Similarly, urinary, peripheral, and adrenal venous concentrations of the hybrid steroids 18-oxocortisol and 18 hydroxycortisol are higher in patients with aldosterone producing adenomas than in bilateral hyperplasia. Differences in the pathophysiology and in clinical and biochemical phenotypes caused by aldosterone producing adenomas and bilateral adrenal hyperplasia may be related to the differential expression of steroidogenic enzymes, and associated to specific underlying somatic mutations. Correct appreciation of differences in steroid profiling between aldosterone producing adenomas and bilateral adrenal hyperplasia may not only contribute to a better understanding of the pathogenesis of primary aldosteronism but may also be helpful for future subtyping of primary aldosteronism. PMID- 26667801 TI - Glucose Metabolism in Primary Aldosteronism. AB - In recent years, an increasing number of studies have revealed deleterious effects of aldosterone via the mineralocorticoid receptor (MR). Especially in patients with primary aldosteronism (PA) a significant higher estimated risk of developing cardiovascular comorbidities and comortalities compared to essential hypertensives was reported. As diabetes mellitus and the metabolic syndrome are one of the major contributors to cardiovascular morbidity and mortality their connection to aldosterone excess became a focus of research in PA patients. Several studies assessed the effect of PA on glucose metabolism, the prevalence of diabetes mellitus, and the effect of PA treatment on both revealing different results. Therefore, we performed an extensive literature research. This review focuses on the current knowledge of the connection between aldosterone excess, glucose homeostasis, and diabetes mellitus in patients with PA. We have highlighted this topic from a pro and contra perspective followed by a summarizing concluding remark. Additionally, we have briefly reviewed the data on possible underlying mechanisms and indicated future considerations on the possible impact of cortisol co-secretion in PA. PMID- 26667802 TI - Parathyroid Gland Function in Primary Aldosteronism. AB - Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. Beyond its effects on intravascular volume and blood pressure, PA causes metabolic alterations and a higher cardiovascular morbidity, which is reduced by PA-directed therapy. Experimental studies demonstrated that mineralocorticoid excess may also influence mineral homeostasis. A role in cardiovascular disease has also been attributed to parathyroid hormone (PTH). Increasing evidence supports a bidirectional interaction between aldosterone and PTH.Primary hyperparathyroidism is associated with arterial hypertension and an increased cardiovascular morbidity and mortality, which might be associated to higher aldosterone values; parathyreoidectomy results in lowered aldosterone and blood pressure levels. PA leads to secondary hyperparathyroidism, which is reversible by PA-directed therapy. A lower bone mineral density and a higher fracture rate were also shown to be reversible by PA-directed therapy. There is a suspicion of a bidirectional interaction between aldosterone and PTH, which might lead to a higher cardiovascular risk. There are more and more reports about coincident PA and primary hyperparathyroidism. From a pathophysiologic point of view this constellation is best characterized as tertiary hyperparathyroidism. Future aspects should further clarify the extent of these endocrine interactions and analyze the influence of this interplay on cardiovascular morbidity and mortality and bone health. PMID- 26667803 TI - Mineralocorticoid Receptor Antagonists and Clinical Outcomes in Primary Aldosteronism: As Good as Surgery? AB - Primary aldosteronism (PA) is detected with increasing frequency in hypertensive patients and is associated with excess cardiovascular, renal, and metabolic complications. For these reasons, appropriate choices for treatment of this endocrine condition are mandatory. Adrenalectomy is safely performed in PA patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone secretion. AVS, however, is a complex procedure and even among worldwide referral centers there are substantial discrepancies for interpretation of results. Also, in the majority of PA patients with lateralized aldosterone secretion, hypertension may persist after adrenalectomy requiring use of additional antihypertensive agents. Treatment with mineralocorticoid receptor antagonists (MRAs) is currently recommended for PA patients with bilateral adrenal disease, but these agents effectively decrease blood pressure also in patients with unilateral disease, although concern remains for possible sex-related side effects. Prospective studies indicate that MRAs have therapeutic values comparable to surgery in the long-term, inasmuch as they effectively correct metabolic abnormalities and subclinical organ damage and reduce the risk of cardiovascular events and renal disease progression. This article overviews the clinical outcomes obtained in patients with PA with use of MRAs. PMID- 26667805 TI - Comparison of vocal outcome following two different procedures for immediate RLN reconstruction. AB - The objective of this study was to compare time-dependent improvements in phonatory function and stroboscopic findings following two different procedures for immediate reconstruction of the recurrent laryngeal nerve (RLN) during neck tumor extirpation. Seventeen patients with neck tumors, consisting of advanced thyroid cancer (n = 15), metastatic neck lymph nodes from other malignant lesions (n = 2), underwent resection of the primary lesion and involved RLN. Immediate RLN reconstruction by either: (1) ansa cervicalis nerve (ACN) to RLN anastomosis (n = 8); or (2) placement of the great auricular nerve (GAN) between the cut ends of the RLN (n = 9) was performed from 2000 to 2011. Phonatory function [maximum phonation time, mean airflow rate (MFR), jitter, and shimmer) and stroboscopic findings (regularity, amplitude, and glottal gap) were examined at 1, 6, and 12 months postoperatively. Stroboscopic findings were assessed by two otolaryngologists and one speech pathologist. There were no significant differences in any parameter for either phonatory function or stroboscopic findings between ACN and GAN with the exception of jitter and shimmer, in which ACN was superior to GAN at 1 month postoperatively. All parameters improved significantly between 1 and 12 months postoperatively for both phonatory function and stroboscopic findings (P < 0.05). Either method of immediate RLN reconstruction at the time of neck tumor extirpation (i.e., ACN or GAN) provided both excellent long-term postoperative phonatory function and stroboscopic findings, and there was little difference in vocal outcome between the two procedures. PMID- 26667804 TI - Atorvastatin treatment improves effects of implanted mesenchymal stem cells: meta analysis of animal models with acute myocardial infarction. AB - BACKGROUND: Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies. METHODS: Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI. RESULTS: In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P < 0.01) with heterogeneity (P = 0.28; P >0.05) and inconsistency (I(2): 22 %). CONCLUSIONS: Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies. PMID- 26667806 TI - A chemosynthetic weed: the tubeworm Sclerolinum contortum is a bipolar, cosmopolitan species. AB - BACKGROUND: Sclerolinum (Annelida: Siboglinidae) is a genus of small, wiry deep sea tubeworms that depend on an endosymbiosis with chemosynthetic bacteria for their nutrition, notable for their ability to colonise a multitude of reducing environments. Since the early 2000s, a Sclerolinum population has been known to inhabit sediment-hosted hydrothermal vents within the Bransfield Strait, Southern Ocean, and whilst remaining undescribed, it has been suggested to play an important ecological role in this ecosystem. Here, we show that the Southern Ocean Sclerolinum population is not a new species, but more remarkably in fact belongs to the species S. contortum, first described from an Arctic mud volcano located nearly 16,000 km away. RESULTS: Our new data coupled with existing genetic studies extend the range of this species across both polar oceans and the Gulf of Mexico. Our analyses show that the populations of this species are structured on a regional scale, with greater genetic differentiation occurring between rather than within populations. Further details of the external morphology and tube structure of S. contortum are revealed through confocal and SEM imaging, and the ecology of this worm is discussed. CONCLUSIONS: These results shed further insight into the plasticity and adaptability of this siboglinid group to a range of reducing conditions, and into the levels of gene flow that occur between populations of the same species over a global extent. PMID- 26667807 TI - Reliability and Validity of the Spence Children's Anxiety Scale for Parents in Mainland Chinese Children and Adolescents. AB - This study examined the psychometric properties of the Spence Children's Anxiety Scale for Parents (SCAS-P) in 1943 father-mother dyads and 1785 students. Results of confirmatory factor analyses for SCAS-P were in favour of the original model with six correlated factors. The internal consistency of SCAS-P was acceptable (alpha = .63-.91), and the test-retest reliability was acceptable (r = .46-.72). The convergent and divergent validity of SCAS-P was supported by significant correlations with an internalizing subscale to a greater extent than with an externalizing subscale. Congruent validity was supported by significant correlations between father and mother reports (r = .60-.71) and child and parent reports (r = .25-.42). Significant differences between community and clinical samples supported the discriminant validity. Adolescents showed higher anxiety levels than children, and girls showed higher anxiety levels than boys. Our findings suggest that the SCAS-P is a suitable parent instrument to measure child anxiety symptoms in Mainland Chinese children and adolescents. PMID- 26667809 TI - A new award: the European Spine Journal Max Aebi Award for Clinical Sciences. PMID- 26667810 TI - Multiple cervical hemivertebra resection and staged thoracic pedicle subtraction osteotomy in the treatment of complicated congenital scoliosis. AB - PURPOSE: To present our experience of staged correction with multiple cervical hemivertebra resection and thoracic pedicle subtraction osteotomy (PSO) treating a rare and complicated congenital scoliosis. METHODS: A 14-year-old male presented with progressive torticollis and spine deformity. The malformation developed since birth, and back pain after long-time sitting or exercise arose since 6 months before, which was unsuccessfully treated by physiotherapy. X-ray showed a right cervical curve of 60 degrees and a left compensatory thoracic curve of 90 degrees . Three-dimensional computed tomography (3-D CT) scan revealed three semi-segmented hemivertebrae (C4, C5 and C6) on the right side. Based on our staged strategy, the three consecutive cervical hemivertebrae, as the major pathology causing the deformity, were firstly resected by the combined posterior and anterior approach. Six months later, T6 PSO osteotomy was used to correct the structural compensatory thoracic curve. RESULTS: The cervical curve was reduced to 23 degrees while the thoracic curve to 60 degrees after the first-stage surgery, and the thoracic curve was further reduced to 30 degrees after the second-stage surgery. The radiograph at 5-year follow-up showed that both the coronal and sagittal balance were well restored and stabilized, with the occipital tilt reduced from 12 degrees to 0 degrees . CONCLUSIONS: Our strategy may provide an option for similar cases with multiple consecutive cervical hemivertebrae and a large structural compensatory thoracic curve, which proved to achieve excellent correction in both the coronal and sagittal planes with acceptable neurologic risk. PMID- 26667811 TI - Erratum to: Clinically orientated classification incorporating shoulder balance for the surgical treatment of adolescent idiopathic scoliosis. PMID- 26667812 TI - Surgical management of intractable spasticity. AB - BACKGROUND: Spasticity is motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex, as one component of the upper motor neuron syndrome. PURPOSE: This study aimed at comparing between spinally based (dorsal rhizotomy) versus peripherally based (selective neurotomy) surgical procedures in management of hypertonia in the lower limbs of pediatrics. METHODS: Over a 3-year period, 50 children with intractable, lower limb spasticity were prospectively treated by selective neurotomy (group A, 35 patients) and dorsal rhizotomy (group B, 15 patients) with 6 months' follow-up period. RESULTS: The operative duration was longer with dorsal rhizotomy with mean of 292.2 min versus 76.8 min with neurotomy (P = 0.001) and the hospital stay of dorsal rhizotomy was longer with mean of 6.2 days versus 1.7 days with neurotomy (P = 0.001). Muscles power exhibited significant improvement in 53.3% of the total rhizotomies (P = 0.001). Following neurotomies; muscle tone showed marked improvement in 69.3% muscles which had normal tone and 31.9% of muscles had mild spasticity (P = 0.001). The H/M ratio following dorsal rhizotomies showed marked reduction of the ratio, and the mean was 0.11 versus 0.58 preoperatively. CONCLUSION: Both neurotomies and dorsal rhizotomies were safe surgical procedures and were provided with good improvement in respect of: muscle power, severity of spasticity, patient's ambulation, gait, range of joint movement, associated pain, functional disability, and nerve excitability with no significant difference between both procedures. PMID- 26667813 TI - Upregulated myocardial CXCR4-expression after myocardial infarction assessed by simultaneous GA-68 pentixafor PET/MRI. PMID- 26667815 TI - Caffeine does not significantly reduce the sensitivity of vasodilator stress myocardial perfusion imaging. PMID- 26667816 TI - Virtual-Experimental 2DE Approach in Chromosome-Centric Human Proteome Project. AB - To obtain more information about human proteome, especially about proteoforms (protein species) coded by 18th chromosome, we separated proteins from human cancer cell line (HepG2) by two-dimensional gel electrophoresis (2DE). Initially, proteins in major spots were identified by MALDI-MS peptide mass fingerprinting. According to parameters (pI/Mw) of identified proteins the gel was calibrated. Using this calibrated gel, a virtual 2D map of proteoforms coded by Chromosome 18 was constructed. Next, the produced gel was divided into 96 sections with determined coordinates. Each section was cut, shredded, and treated by trypsin according to mass-spectrometry protocol. After protein identification by shotgun mass spectrometry using ESI LC-MS/MS, a list of 20 462 proteoforms (product of 3774 genes) was generated. Among them, 165 proteoforms are representing 39 genes of 18th chromosome. The 3D graphs showing the distribution of different proteoforms from the same gene in 2D map were generated. This is a first step in creation of 2DE-based knowledge database of proteins coded by 18th chromosome. PMID- 26667814 TI - Principles and techniques of imaging in identifying the substrate of ventricular arrhythmia. AB - Life-threatening ventricular arrhythmias (VA) are a major cause of death in patients with cardiomyopathy. To date, impaired left ventricular ejection fraction remains the primary criterion for implantable cardioverter-defibrillator therapy to prevent sudden cardiac death. In recent years, however, advanced imaging techniques such as nuclear imaging, cardiac magnetic resonance imaging, and computed tomography have allowed for a more detailed evaluation of the underlying substrate of VA. These imaging modalities have emerged as a promising approach to assess the risk of sudden cardiac death. In addition, non-invasive identification of the critical sites of arrhythmias may guide ablation therapy. Typical anatomical substrates that can be evaluated by multiple advanced imaging techniques include perfusion abnormalities, scar and its border zone, and sympathetic denervation. Understanding the principles and techniques of different imaging modalities is essential to gain more insight in their role in identifying the arrhythmic substrate. The current review describes the principles of currently available imaging techniques to identify the substrate of VA. PMID- 26667817 TI - Redirection of Metabolic Flux into Novel Gamma-Aminobutyric Acid Production Pathway by Introduction of Synthetic Scaffolds Strategy in Escherichia Coli. AB - In general, gamma-aminobutyric acid (GABA) pathway involves the decarboxylation of glutamate, which is produced from sugar by Corynebacterium fermentation. GABA can be used for the production of pharmaceuticals and functional foods. Due to the increasing demand of GABA, it is essential to create an effective alternative pathway for the GABA production. In this study, Escherichia coli were engineered to produce GABA from glucose via GABA shunt, which consists of succinate dehydrogenase, succinate-semialdehyde dehydrogenase, and GABA aminotransferase. The three enzymes were physically attached to each other through a synthetic scaffold, and the Krebs cycle flux was redirected to the GABA pathway. By introduction of synthetic scaffold, 0.75 g/l of GABA was produced from 10 g/l of glucose at 30 degrees C and pH 6.5. The inactivation of competing metabolic pathways provided 15.4 % increase in the final GABA concentration. PMID- 26667819 TI - Screening of patients with augmented renal clearance in ICU: taking into account the CKD-EPI equation, the age, and the cause of admission. AB - BACKGROUND: In ICU patients with normal serum creatinine (SCr), a state of increased renal drug excretion has been described (creatinine clearance >=130 ml/min/1.73 m(2)), and named augmented renal clearance (ARC). In ICU patients, the accuracy of GFR estimates is insufficient. However, in clinical practice, the physician has not at one's disposal patient measured creatinine clearance (CrCl) when prescribing. The primary objective of this study was to assess the accuracy of 4 formulas to estimate GFR (Cockcroft-Gault (CG), Robert, sMDRD, and CKD-EPI formulas) with other covariates to detect ARC in ICU patients. METHODS: We enroled 360 consecutive ICU patients with normal SCr in this prospective observational study conducted in a primary teaching hospital. Comparisons between CrCl values and 4 estimated GFR (eGFR) formulas were estimated. RESULTS: In these 360 patients, ARC was observed in 33 % of patients most of them trauma. Individual predictive values of equations were poor and the phenomenon increased in ARC subgroup. CG and CKD-EPI were more accurate to detect an ARC. Multivariable analysis showed that the best-fitting model included 3 factors independently correlated to ARC: trauma patients, cut-off values of age <=58 years, and CKD-EPI more than 108 ml/min/1.73 m(2). CONCLUSIONS: In ICU patients with normal SCr, eGFR formulas are imprecise in assessing CrCl. If measured CrCl must be ideally used to detect modifications of the renal function, in clinical practice, age, reason for admission, and CKD-EPI could be used as screening tool to identify ARC. PMID- 26667820 TI - The Smart Health Initiative in China: The Case of Wuhan, Hubei Province. AB - To introduce smart health in Wuhan, and provide some references for other cities. As the largest mega-city in central China, Wuhan is investing large amounts of resources to push forward the development of Smart Wuhan and Health Wuhan, and it has unique features. It is one of the centerpieces of China's New Healthcare Reform, and great hope is put on it to help solve the conflict between limited healthcare resources and the large population of patients. How to plan and design smart health is important. The construction of Wuhan Smart Health includes some aspects as follows, like requirement analysis, the establishment of objectives and blueprint, the architecture design of regional health information platform, evaluation and implementation, problems and solutions, and so on. Wuhan Smart Health has obtained some achievements in health network, information systems, resident's health records, information standard, and the first phase of municipal health information platform. The focus of this article is the whole construction process of smart health in Wuhan. Although there are some difficulties during this period, some smart health services and management have been reflected. Compared with other cities or countries, Wuhan Smart Health has its own advantages and disadvantages. This study aims to provide a reference for other cities. Because smart health of Wuhan is characteristic in construction mode. Though still in the initial stage, it has great potentials in the future. PMID- 26667818 TI - Transcriptome-wide high-throughput deep m(6)A-seq reveals unique differential m(6)A methylation patterns between three organs in Arabidopsis thaliana. AB - BACKGROUND: m(6)A is a ubiquitous RNA modification in eukaryotes. Transcriptome wide m(6)A patterns in Arabidopsis have been assayed recently. However, differential m(6)A patterns between organs have not been well characterized. RESULTS: Over two-third of the transcripts in Arabidopsis are modified by m(6)A. In contrast to a recent observation of m(6)A enrichment in 5' mRNA, we find that m(6)A is distributed predominantly near stop codons. Interestingly, 85 % of the modified transcripts show high m(6)A methylation extent compared to their transcript level. The 290 highly methylated transcripts are mainly associated with transporters, stress responses, redox, regulation factors, and some non coding RNAs. On average, the proportion of transcripts showing differential methylation between two plant organs is higher than that showing differential transcript levels. The transcripts with extensively higher m(6)A methylation in an organ are associated with the unique biological processes of this organ, suggesting that m(6)A may be another important contributor to organ differentiation in Arabidopsis. Highly expressed genes are relatively less methylated and vice versa, and different RNAs have distinct m(6)A patterns, which hint at mRNA fate. Intriguingly, most of the transposable element transcripts maintained a fragmented form with a relatively low transcript level and high m(6)A methylation in the cells. CONCLUSIONS: This is the first study to comprehensively analyze m(6)A patterns in a variety of RNAs, the relationship between transcript level and m(6)A methylation extent, and differential m(6)A patterns across organs in Arabidopsis. PMID- 26667822 TI - Trends, correlates, and disease patterns of antipsychotic use among elderly persons in Taiwan. AB - INTRODUCTION: We used the population-based database to investigate the trends, correlates, and disease patterns of antipsychotic use among elderly people in Taiwan. METHODS: The National Health Research Institutes provided a database of 1,000,000 random subjects for health service studies. We analyzed a sample of subjects over the age of 65 years from 1997 to 2005. The trends in and factors associated with antipsychotic use were detected. We also examined the proportions of antipsychotics used for psychiatric and medical disorders. RESULTS: The 1-year prevalence of antipsychotic use in elderly persons increased from 9.8% in 1997 to 12.8% in 2005. The prevalence of first-generation antipsychotic (FGA) use increased from 9.8% to 11.6%, and the prevalence of second-generation antipsychotic (SGA) use increased greatly from 0.01% to 2.02%. Higher prevalence of both FGAs and SGAs were associated with age and higher Charlson Comorbidity Index scores. Psychiatric disorders were commonly found in SGA users (80.8%), whereas only 19.3% of the FGA users had psychiatric disorders. Among the major psychiatric disorders, greater proportions of antipsychotic use were for senile and presenile organic psychotic conditions, other organic psychotic conditions, and affective psychoses. FGAs were much more commonly prescribed for nonpsychiatric disorders, including diseases of symptoms, signs, and ill-defined conditions, the digestive system, and the respiratory system. DISCUSSION: The prevalence of antipsychotic use, particularly the use of SGAs, increased greatly from 1997 to 2005 among elderly persons in Taiwan. SGAs were most used by subjects with psychiatric disorders, and FGAs were most used by those with nonpsychiatric disorders. PMID- 26667821 TI - Cytoplasmic levels of cFLIP determine a broad susceptibility of breast cancer stem/progenitor-like cells to TRAIL. AB - BACKGROUND: The clinical application of TRAIL receptor agonists as a novel cancer therapy has been tempered by heterogeneity in tumour responses. This is illustrated in breast cancer, where TRAIL is cytotoxic in cell lines of mesenchymal origin but refractory in lines with an epithelial-like phenotype. However, it is now evident that intra-tumour heterogeneity includes a minority subpopulation of tumour-initiating stem/progenitor-like cells (CSCs) that possess mesenchymal characteristics. We hypothesised therefore that TRAIL may target these phenotypically distinct CSC-like cells that are common to most - if not all - breast cancers, thus impacting on the source of malignancy in a much broader range of breast tumour subtypes than previously envisaged. METHODS: We used colony formation, tumoursphere, flow cytometry and xenograft tumour initiation assays to observe the TRAIL sensitivity of CSC-like cells in a panel of two mesenchymal-like (TRAIL-sensitive) and four epithelial-like (TRAIL-resistant) breast cancer cell lines. Subcellular levels of the endogenous TRAIL inhibitor, cFLIP, were determined by western blot and immunofluorescence microscopy. The effect of the subcellular redistribution of cFLIP on TRAIL sensitivity and Wnt signalling was determined using cFLIP localisation mutants and the TOPFlash reporter assay respectively. RESULTS: TRAIL universally suppressed the clonal expansion of stem/progenitors in all six of the breast cancer cell lines tested, irrespective of their phenotype or overall sensitivity to TRAIL. A concomitant reduction in tumour initiation was confirmed in the TRAIL-resistant epithelial cell line, MCF-7, following serial dilution xenotransplantation. Furthermore TRAIL sensitivity of breast CSCs was inversely proportional to the relative cytoplasmic levels of cFLIP while overexpression of cFLIP in the cytosol using subcellular localization mutants of cFLIP protected these cells from cytotoxicity. The accumulation of nuclear cFLIP on the other hand did not influence TRAIL cytotoxicity but instead promoted Wnt-dependent signalling. CONCLUSION: These data propose a novel role for TRAIL as a selective CSC agent with a broad specificity for both epithelial and mesenchymal breast tumour subtypes. Furthermore we identify a dual role for cFLIP in the maintenance of breast CSC viability, dependent upon its subcellular distribution. PMID- 26667823 TI - New Italian immunisation plan is built on scientific evidence: Carlo Signorelli and colleagues reply to news article by Michael Day. PMID- 26667824 TI - Barriers encountered during the implementation of a policy guideline on the vaccination of health care workers during the 2013-2014 measles outbreak in the Netherlands: a qualitative study. AB - BACKGROUND: In 2013 the Netherlands faced a measles epidemic, during which more than 2600 individuals were infected, including 19 health care workers (HCW). Vaccinating health care workers can lead to benefits on both the individual and public health level, underscoring the need for HCW vaccination. In June of 2013 the Dutch National Institute for Public Health and the Environment (RIVM) developed a measles guideline (MG) that advised Dutch hospitals to strengthen their policies concerning measles vaccination of HCWs. A key problem with guidelines, however, is adherence, which can be due to several barriers. The objective of this research was to identify the barriers that Dutch hospital professionals encountered during the implementation of this policy guideline, in order to improve the implementation of similar policies in the future. METHODS: In-depth interviews (n = 9) were conducted with 12 hospital health care professionals involved with prevention and control of communicable diseases. These participants represented ten different Dutch hospitals located in eight of the twelve different provinces. Participants were asked about their experiences during the 2013-2014 measles epidemic regarding infection prevention measures, including vaccination of HCWs, with a specific focus on barriers to the implementation of the RIVM guideline. RESULTS: The implementation of the MG was impeded by several (types of) barriers. First, barriers were found related to knowledge and attitude, and included lack of agreement, barriers associated with leadership and issues related to evidence-based decision making. Second, barriers related to characteristics of the guideline, mostly related to unclear or missing guideline content. Finally, contextual and social factors such as human and financial resources, belief systems, physical facilities and technical support, and national views on vaccination policies also play an important role in policy implementation. CONCLUSIONS: This study has provided valuable insights into the barriers infection prevention specialists encounter during the implementation of new policies concerning vaccination of HCWs in times of a major outbreak. Moreover, this study exposed the complexity and breadth of barriers that are of importance when implementing vaccination policies in the hospital setting. In order to improve the implementation of similar policies in the future, guideline developers and health care providers and administrators alike should aim to eliminate or minimise these identified barriers by taking into account the suggestions made by the authors. PMID- 26667826 TI - The preventive treatment of recurrent stone-formation: how can we improve compliance in the treatment of patients with recurrent stone disease? AB - Whether prevention of Urolithiasis is worthwhile is the outcome of the balance between efficacy of prevention and costs and efforts related of respectively prevention and treatment of a new stone. Well controlled trials demonstrate that effective prevention of new stone formation is possible using medical treatment and lifestyle interventions. In long-term general practice the results obtained with preventive interventions is disappointing. Low and diminishing long-term compliance to the intervention is a major cause for this. Both the long-term aspect and the natural resistance to lifestyle changes contribute to this low compliance. From an analysis of the existing data on trials of preventive interventions and from experiences obtained in other patient groups where lifestyle changes are applied I will make the case that self-empowerment of the patient using m-health lifestyle coaching (a smart phone application) can considerably enhance the level of prevention that is obtained in general practice. In conclusion, I will describe what features will improve usage and efficacy of such an app. PMID- 26667827 TI - Predictors of Change in Dyspnea Level in Acute Exacerbations of COPD. AB - The aim of this study was to identify factors related to changes in dyspnoea level in the acute and short-term periods after acute exacerbation of chronic obstructive pulmonary disease. This was a prospective cohort study of patients with symptoms of acute chronic obstructive pulmonary disease exacerbation who attended one of 17 hospitals in Spain between June 2008 and September 2010. Clinical data and patient reported measures (dyspnoea level, health-related quality of life, anxiety and depression levels, capacity to perform physical activity) were collected from arrival to the emergency department up to a week after the visit in discharged patients and to discharge in admitted patients (short term). Main outcomes were time course of dyspnoea over the acute (first 24 hours) and short-term periods, mortality and readmission within 2 months of the index episode. Changes in dyspnoea in both periods were related capacity to perform physical activity as well as clinical variables. Short-term changes in dyspnoea were also related to dyspnoea at 24 hours after the ED visit, and anxiety and depression levels. Dyspnoea worsening or failing to improve over the studied periods was associated with poor clinical outcomes. Patient-reported measures are predictive of changes in dyspnoea level. PMID- 26667828 TI - Are vacuum-filtrated reduced graphene oxide membranes symmetric? AB - Graphene or reduced graphene oxide (rGO) membrane-based materials are promising for many advanced applications due to their exceptional properties. One of the most widely used synthesis methods for rGO membranes is vacuum filtration of graphene oxide (GO) on a filter membrane, followed by reduction, which shows great advantages such as operational convenience and good controllability. Despite vacuum-filtrated rGO membranes being widely used in many applications, a fundamental question is overlooked: are the top and bottom surfaces of the membranes formed at the interfaces with air and with the filter membrane respectively symmetric or asymmetric? This work, for the first time, reports the asymmetry of the vacuum-filtrated rGO membranes and discloses the filter membranes' physical imprint on the bottom surface of the rGO membrane, which takes place when the filter membrane surface pores have similar dimension to GO sheets. This result points out that the asymmetric surface properties should be cautiously taken into consideration while designing the surface-related applications for GO and rGO membranes. PMID- 26667829 TI - Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation. AB - Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1 null genotypes alone and in combination may predict the acquisition of hepatotoxicity. PMID- 26667831 TI - Biobutanol production from C5/C6 carbohydrates integrated with pervaporation: experimental results and conceptual plant design. AB - In this study, a simulated lignocellulosic hydrolyzate was used in a continuous two-stage fermentor setup for production of acetone, butanol and ethanol. An organophilic pervaporation unit was coupled to the second fermentor. The dilution rate in the first fermentor was kept constant at 0.109 h(-1), while the dilution rate in the second fermentor was gradually decreased from 0.056 to 0.020 h(-1). Glucose was completely consumed, while 61% of the xylose was consumed at the lowest dilution rate, leading to an overall solvent productivity of 0.65 g L(-1) h(-1) and a high concentration of 185 g kg(-1) solvents in the permeate in the last fermentation zone during 192 h. Based on the experimental results, a process integrated with organophilic pervaporation was conceptually designed and compared with a base-case. Chemcad simulations indicate an energy reduction of ~50% when organophilic pervaporation is used. This study also demonstrates significant reductions in process flows and energy consumption by the use of organophilic pervaporation as in situ product recovery technology. PMID- 26667832 TI - Inside the Diabetic Brain: Role of Different Players Involved in Cognitive Decline. AB - Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication. PMID- 26667833 TI - Antidiarrhoeal, antimicrobial and antioxidant effects of myrtle berries (Myrtus communis L.) seeds extract. AB - OBJECTIVES: The present study was carried out to determine the antidiarrheal effects of myrtle (Myrtus communis L.) berries seeds aqueous extract (MBSAE) from Tunisia as well as the involvement of its antimicrobial and antioxidant properties in such protection. METHODS: Adult male wistar rats were used and divided into six groups of ten each: control, Castor oil, Castor oil + Loperamide and Castor oil + various doses of MBSAE. Animals were per orally (p.o.) pre treated with MBSAE for one hour and intoxicated by castor oil acute oral administration. KEY FINDINGS: Our results demonstrated that the MBSAE is rich in total and condensed tannins and exhibited a broad spectrum of antibacterial activity. In vivo, we found that MBSAE administration induced a significant dose dependent protection against diarrhoea and intestinal fluid accumulation. Castor oil-induced intestinal hypersecretion was accompanied by an oxidative stress status in the intestine. More importantly, we showed that acute diarrhoea was accompanied by an increase in intestinal mucosa hydrogen peroxide (H2 O2 ), calcium and free iron levels while MBSAE pre-treatment reversed all castor oil induced intracellular mediators disturbances. CONCLUSIONS: We suggest that MBSAE had a potent protective effects against castor oil-induced acute diarrhoea due in part to its antioxidant and antimicrobial properties. PMID- 26667830 TI - Genotype-guided tacrolimus dosing in African-American kidney transplant recipients. AB - Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5*3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5*6 and CYP3A5*7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5*1, *3, *6 and *7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy. PMID- 26667834 TI - The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor beta1 in Hepatic Stellate Cells. AB - The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway. PMID- 26667835 TI - The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations. AB - Cerebral malaria (CM) is a neurological complication of infection with Plasmodium falciparum that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in IL17A, IL17F, and IL17RA (which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that IL17F reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (P = 0.004; odds ratio [OR] = 3.12), IL17F rs4715291 (P = 0.004; OR = 2.82), IL17RA rs12159217 (P = 0.01; OR = 2.27), and IL17RA rs41396547 (P = 0.026; OR = 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs, IL17F rs6913472 (P = 0.03; OR = 1.39), IL17RA rs12159217 (P = 0.01; OR = 1.52), and IL17RA rs41396547 (P = 0.04; OR = 3.50). We also found that one additional SNP, IL17RA rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (P = 0.002; OR = 4.12 in the combined sample). We excluded the possibility that SNPs outside IL17F and IL17RA, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of IL17F rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that IL17F and IL17RA polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM. PMID- 26667836 TI - The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis. AB - C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRgamma as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen Blastomyces dermatitidis. MCL(-/-) mice showed impaired vaccine resistance against B. dermatitidis infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes in vitro. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with B. dermatitidis. PMID- 26667837 TI - Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium. AB - Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNgammars2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNgammars2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNgammars2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNgammars2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNgammars2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNgamma) mRNA (P = 0.049) and IFNgamma and tumor necrosis factor alpha (TNF alpha) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 . 10(-4) and P50.000 permutation test = 9.34 . 10( 5)). These findings suggest that the IFNgammars2069705 SNP influences the risk of IA and that predictive models built with IFNgamma, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies. PMID- 26667838 TI - A Coming of Age Story: Chlamydia in the Post-Genetic Era. AB - Chlamydia spp. are ubiquitous, obligate, intracellular Gram-negative bacterial pathogens that undergo a unique biphasic developmental cycle transitioning between the infectious, extracellular elementary body and the replicative, intracellular reticulate body. The primary Chlamydia species associated with human disease are C. trachomatis, which is the leading cause of both reportable bacterial sexually transmitted infections and preventable blindness, and C. pneumoniae, which infects the respiratory tract and is associated with cardiovascular disease. Collectively, these pathogens are a significant source of morbidity and pose a substantial financial burden on the global economy. Past efforts to elucidate virulence mechanisms of these unique and important pathogens were largely hindered by an absence of genetic methods. Watershed studies in 2011 and 2012 demonstrated that forward and reverse genetic approaches were feasible with Chlamydia and that shuttle vectors could be selected and maintained within the bacterium. While these breakthroughs have led to a steady expansion of the chlamydial genetic tool kit, there are still roads left to be traveled. This minireview provides a synopsis of the currently available genetic methods for Chlamydia along with a comparison to the methods used in other obligate intracellular bacteria. Limitations and advantages of these techniques will be discussed with an eye toward the methods still needed, and how the current state of the art for genetics in obligate intracellular bacteria could direct future technological advances for Chlamydia. PMID- 26667839 TI - Maresin 1 Biosynthesis and Proresolving Anti-infective Functions with Human Localized Aggressive Periodontitis Leukocytes. AB - Localized aggressive periodontitis (LAP) is a distinct form of early-onset periodontitis linked to periodontal infection with uncontrolled inflammation and leukocyte-mediated tissue destruction. The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPMs). Since the level of the Maresin pathway marker 14-hydroxy-docosahexaenoic acid (14 HDHA) was lower in activated peripheral blood from LAP patients, we investigated the Maresin 1 (MaR1) biosynthetic pathway in these subjects and its role in regulating phagocyte functions. Macrophages from LAP patients had a lower level of expression of 12-lipoxygenase (~30%) and reduced MaR1 (LAP versus healthy controls [HC], 87.8 +/- 50 pg/10(6) cells versus 239.1 +/- 32 pg/10(6) cells). Phagocytosis by LAP macrophages was reduced ~40% compared to that of HC, and killing of periodontal pathogens, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were similarly reduced. LAP neutrophils also displayed slower kinetics (~30%) and decreased maximal phagocytosis (~20% lower) with these pathogens than those of HC. The administration of MaR1 at 1 nM enhanced phagocytosis (31 to 65% increase), intracellular antimicrobial reactive oxygen species production (26 to 71% increase), bacterial killing of these periodontal pathogens (22 to 38% reduction of bacterial titers), and restored impairment of LAP phagocytes. Together, these results suggest that therapeutics targeting the Maresin pathway have clinical utility in treating LAP and other oral diseases associated with infection, inflammation, and altered phagocyte functions. PMID- 26667842 TI - InspIRED by Nature: NADPH-Dependent Imine Reductases (IREDs) as Catalysts for the Preparation of Chiral Amines. AB - Imine reductases (IREDs) are NADPH-dependent oxidoreductases that catalyse the asymmetric reduction of cyclic prochiral imines to amines, with excellent stereoselectivity. Since their discovery, stereocomplementary IREDs have been applied to the production of both (S) and (R) cyclic secondary amines, and the expansion in gene sequences recently identified has hinted at new substrate ranges that extend into acyclic imines and even suggest the possibility of asymmetric reductive amination from suitable ketone and amine precursors. Structural studies of various IREDs are beginning to reveal the complexities inherent in determining substrate range, stereoselectivity and mechanism in these enzymes, which represent a valuable emerging addition to the toolbox of available biocatalysts for chiral amine production. PMID- 26667840 TI - Tailoring a Combination Preerythrocytic Malaria Vaccine. AB - The leading malaria vaccine candidate, RTS,S, based on the Plasmodium falciparum circumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, the Plasmodium berghei homologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria. PMID- 26667843 TI - Stability and properties of the Ru-H system at high pressure. AB - We report on a first-principles study of the phase diagram, structures and properties of the Ru-H system in the H-rich regime over a wide range of pressures. The results show that RuH is thermodynamically stable and can coexist with RuH3 and RuH6 under pressure. RuH and RuH3 stoichiometries exhibit metallic character as a result of notable band structures, while RuH6 is a semiconductor. Strikingly, some hydrogen atoms pairwise couple into H2 units in the RuH6 compound. An estimation of superconducting transition temperature Tc is carried out by applying the Allen-Dynes modified McMillan equation for Fm3[combining macron]m (RuH), Pm3[combining macron]m (RuH3), and Pm3[combining macron]n (RuH3) structures and the resulting Tc reaches 0.41, 3.57 and 1.25 K at different pressures, respectively. PMID- 26667841 TI - Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen. AB - In different bacteria, primarily cytosolic and metabolic proteins are characterized as surface localized and interacting with different host factors. These moonlighting proteins include glycolytic enzymes, and it has been hypothesized that they influence the virulence of pathogenic species. The presence of surface-displayed glycolytic enzymes and their interaction with human plasminogen as an important host factor were investigated in the genome-reduced and cell wall-less microorganism Mycoplasma pneumoniae, a common agent of respiratory tract infections of humans. After successful expression of 19 glycolytic enzymes and production of polyclonal antisera, the localization of proteins in the mycoplasma cell was characterized using fractionation of total proteins, colony blot, mild proteolysis and immunofluorescence of M. pneumoniae cells. Eight glycolytic enzymes, pyruvate dehydrogenases A to C (PdhA-C), glyceraldehyde-3-phosphate dehydrogenase (GapA), lactate dehydrogenase (Ldh), phosphoglycerate mutase (Pgm), pyruvate kinase (Pyk), and transketolase (Tkt), were confirmed as surface expressed and all are able to interact with plasminogen. Plasminogen bound to recombinant proteins PdhB, GapA, and Pyk was converted to plasmin in the presence of urokinase plasminogen activator and plasmin-specific substrate d-valyl-leucyl-lysine-p-nitroanilide dihydrochloride. Furthermore, human fibrinogen was degraded by the complex of plasminogen and recombinant protein PdhB or Pgm. In addition, surface-displayed proteins (except PdhC) bind to human lung epithelial cells, and the interaction was reduced significantly by preincubation of cells with antiplasminogen. Our results suggest that plasminogen binding and activation by different surface-localized glycolytic enzymes of M. pneumoniae may play a role in successful and long-term colonization of the human respiratory tract. PMID- 26667844 TI - Alterations in neural Theory of Mind processing in euthymic patients with bipolar disorder and unaffected relatives. AB - OBJECTIVES: Behavioral deficits in the Theory of Mind (ToM) have been robustly demonstrated in bipolar disorder. These deficits may represent an intermediate phenotype of the disease. The aim of this study was: (i) to investigate alterations in neural ToM processing in euthymic patients with bipolar disorder, and (ii) to examine whether similar effects are present in unaffected relatives of patients with bipolar disorder suggesting that ToM functional activation may be, in part, due to genetic risk for the disease. METHODS: A total of 24 euthymic patients with bipolar disorder, 21 unaffected first-degree relatives, and 81 healthy controls completed a ToM task while undergoing functional magnetic resonance imaging. RESULTS: We observed reduced bilateral activation of the temporoparietal junction (TPJ) and diminished functional fronto-temporoparietal connectivity in patients compared to controls. Relatives tended towards intermediate temporoparietal activity and functional coupling with medial prefrontal areas. There was also evidence for a potentially compensatory enhanced recruitment of the right middle temporal gyrus and stronger connectivity between this region and the medial prefrontal cortex in relatives. CONCLUSIONS: These findings provide further evidence of altered neural ToM processing in euthymic patients with bipolar disorder. Further, our findings in relatives lend support to the idea that altered ToM processing may act as an intermediate phenotype of the disorder. PMID- 26667845 TI - Adequacy of initiating TNF antagonists within 3 weeks of starting latent tuberculosis infection treatment in patients with immune-mediated inflammatory diseases. AB - Background This study investigated whether tumour necrosis factor (TNF) antagonists should be initiated within 3 weeks of latent tuberculosis infection (LTBI) treatment in patients with immune-mediated inflammatory disease (IMID). Methods Between June 2004 and October 2013, a total of 1521 IMID patients were screened for LTBI before initiating anti-TNF therapy at a tertiary referral centre in South Korea. Their medical records were retrospectively reviewed. Results A total of 411 patients received LTBI treatment before receiving TNF antagonists between June 2004 and October 2013. The mean age of the 411 study subjects was 44.5 years and 261 (63.5%) were male. Anti-TNF agent was initiated in 61 patients (14.8%) within 3 weeks after chemoprophylaxis for LTBI, but 3 weeks later in the remaining 350 patients (85.2%). These two groups were comparable in terms of baseline characteristics, but differed significantly in the mean duration of LTBI treatment before commencing anti-TNF therapy (8 vs 30 days, p < 0.001). A total of six patients developed TB during the follow-up period and received anti-TNF agents 3 weeks after initiation of LTBI treatment. None of the patients who commenced TNF antagonist therapy within 3 weeks of LTBI treatment developed TB. Conclusions TNF antagonists may be initiated within 3 weeks of commencing LTBI treatment in IMID patients. PMID- 26667846 TI - A Large-scale Survey of CRF55_01B from Men-Who-Have-Sex-with-Men in China: implying the Evolutionary History and Public Health Impact. AB - The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China, involving the co-circulation of several different lineages of HIV-1 strains, including subtype B and CRF01_AE. This expansion has created conditions that facilitate the generation of new recombinant strains. A molecular epidemiologic survey among MSM in 11 provinces/cities around China was conducted from 2008 to 2013. Based on pol nucleotide sequences, a total of 19 strains (1.95%) belonged to the CRF55_01B were identified from 975 MSM in 7 provinces, with the prevalence range from 1.5% to 12.5%. Near full length genome (NFLG) sequences from six epidemiologically-unlinked MSM were amplified for analyzing evolutionary history, an identical genome structure composed of CRF01_AE and subtype B with four unique recombination breakpoints in the pol region were identified. Bayesian molecular clock analyses for both CRF01_AE and B segments indicated that the estimated time of the most recent common ancestors of CRF55_01B was around the year 2000. Our study found CRF55_01B has spread throughout the most provinces with high HIV-1 prevalence and highlights the importance of continual surveillance of dynamic changes in HIV-1 strains, the emergence of new recombinants, and the need for implementing effective prevention measures specifically targeting the MSM population in China. PMID- 26667848 TI - Neuropsychological profile in new-onset benign epilepsy with centrotemporal spikes (BECTS): Focusing on executive functions. AB - PURPOSE: Increased evidence of subnormal neuropsychological functioning in new onset childhood epilepsy has been obtained, although results are still rare and controversial. With a prospective study, we aimed to define the very early neuropsychological profile of children with benign epilepsy with centrotemporal spikes (BECTS), including executive functions (EF) because of their key role in learning. Additionally, we enrolled drug-naive children, with a NREM sleep frequency of discharges <85% and with a Performance Intelligence Quotient equal or superior to 85, in order to exclude additional effects on the neuropsychological functioning. METHODS: Fifteen school-aged children with BECTS (mean age: 8.8years, standard deviation [SD]: 2.4years) and fifteen healthy children (mean age: 9.2years, [SD]: 2.5years) were enrolled and assessed with a comprehensive neuropsychological battery. The assessment included domain-specific standardized tests of language, EF, academic skills, visuomotor and visuospatial skills, and short-term memory. A p-value<0.05 was considered significant. RESULTS: Significant differences between patients and controls emerged with respect to 3 domains. Language was affected in color naming (p=.026), spoonerism (p=.003), and phonemic synthesis (p=.009). Executive functions appeared inadequate in the five point test with respect to the number of correct figures (p=.003) and errors (p=.008). In the domain of academic skills, significant differences between groups emerged regarding the number of mistakes in nonword writing (p=.001), nonword reading speed (p=.027), nonword reading number of mistakes (p=.019), and word reading errors (p=.023). DISCUSSION: Results showed that children with new-onset BECTS may demonstrate a range of neuropsychological dysfunctions, particularly affecting executive attention, despite a normal IQ, a low frequency of NREM sleep discharges, and the absence of drugs. These difficulties indicate a frontal dysfunction with cascading effects on language and academic skills. The inclusion of EF in the assessment battery and in the intervention since the very onset is warranted in order to avoid further and persistent academic difficulties. PMID- 26667850 TI - Tumour immunology: Intestinal bacteria are in command. PMID- 26667849 TI - DNA repair, genome stability and cancer: a historical perspective. AB - The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy. PMID- 26667851 TI - Leukaemia: Breaking tradition with PARP inhibition. PMID- 26667852 TI - Oncogenes: One of these things is not like the others. PMID- 26667853 TI - Predicting future emergency department visits and hospitalizations for asthma using the Pediatric Asthma Control and Communication Instrument - Emergency Department version (PACCI-ED). AB - OBJECTIVE: Emergency departments (EDs) are potential settings for interventions to improve asthma outcomes. Screening tools can identify children at risk of future morbidity. Our objective was to determine the predictive validity of the Pediatric Asthma Control and Communication Instrument - Emergency Department version (PACCI-ED) for future asthma-related ED visits and hospitalizations. METHODS: This was a retrospective cohort study of 108 children 1-17 years old who visited an ED for asthma and completed the PACCI-ED. The PACCI-ED queries parents about prior 12-month ED visits, hospitalizations, steroid use, perceived asthma morbidity and burden, and asthma control (over prior 1-2 weeks). The primary outcome was subsequent ED visits and hospitalizations within 1 year of enrollment. Poisson regression was used to model PACCI-ED questions for future ED visits controlling for age and socioeconomic status. RESULTS: Reported ED visits predicted future ED visits (adjusted incidence rate ratio (aIRR) 3.1, 95% confidence interval (CI): 1.3-7.2) but not future hospitalizations. Reported hospitalizations predicted future ED visits (aIRR 3.3; 95% CI 1.7-6.3) and hospitalizations (aIRR 6.4; 95% CI 2.3-17.6). The remaining PACCI-ED questions did not predict future ED visits or hospitalizations. CONCLUSIONS: The PACCI-ED risk domain was the only domain that predicted future asthma ED visits and hospitalizations. Questions about previous ED visits and hospitalizations are the most effective questions when screening children with asthma in EDs for the risk of future health-care use. PMID- 26667854 TI - Professional Medical Writing: A Tool for High Quality Publications. PMID- 26667855 TI - [Electronic Cigarette: Position of the Portuguese Society of Pneumology]. PMID- 26667856 TI - [Analysis of the Cochrane Review: Interventions for Improving Upper Limb Function after Stroke. Cochrane Database Syst Rev. 2014,11:CD010820]. AB - Impairment of the upper limbs is quite frequent after stroke, making rehabilitation an essential step towards clinical recovery and patient empowerment. This review aimed to synthetize existing evidence regarding interventions for upper limb function improvement after Stroke and to assess which would bring some benefit. The Cochrane Database of Systematic Reviews, the Database of Reviews of Effects and PROSPERO databases were searched until June 2013 and 40 reviews have been included, covering 503 studies, 18 078 participants and 18 interventions, as well as different doses and settings of interventions. The main results were: 1- Information currently available is insufficient to assess effectiveness of each intervention and to enable comparison of interventions; 2- Transcranial direct current stimulation brings no benefit for outcomes of activities of daily living; 3- Moderate-quality evidence showed a beneficial effect of constraint-induced movement therapy, mental practice, mirror therapy, interventions for sensory impairment, virtual reality and repetitive task practice; 4- Unilateral arm training may be more effective than bilateral arm training; 5- Moderate-quality evidence showed a beneficial effect of robotics on measures of impairment and ADLs; 6- There is no evidence of benefit or harm for technics such as repetitive transcranial magnetic stimulation, music therapy, pharmacological interventions, electrical stimulation and other therapies. Currently available evidence is insufficient and of low quality, not supporting clear clinical decisions. High-quality studies are still needed. PMID- 26667857 TI - Prediction of Success in External Cephalic Version under Tocolysis: Still a Challenge. AB - INTRODUCTION: External cephalic version is a procedure of fetal rotation to a cephalic presentation through manoeuvres applied to the maternal abdomen. There are several prognostic factors described in literature for external cephalic version success and prediction scores have been proposed, but their true implication in clinical practice is controversial. We aim to identify possible factors that could contribute to the success of an external cephalic version attempt in our population. MATERIAL AND METHODS: We retrospectively examined 207 consecutive external cephalic version attempts under tocolysis conducted between January 1997 and July 2012. We consulted the department's database for the following variables: race, age, parity, maternal body mass index, gestational age, estimated fetal weight, breech category, placental location and amniotic fluid index. We performed descriptive and analytical statistics for each variable and binary logistic regression. RESULTS: External cephalic version was successful in 46.9% of cases (97/207). None of the included variables was associated with the outcome of external cephalic version attempts after adjustment for confounding factors. DISCUSSION: We present a success rate similar to what has been previously described in literature. However, in contrast to previous authors, we could not associate any of the analysed variables with success of the external cephalic version attempt. We believe this discrepancy is partly related to the type of statistical analysis performed. CONCLUSIONS: Even though there are numerous prognostic factors identified for the success in external cephalic version, care must be taken when counselling and selecting patients for this procedure. The data obtained suggests that external cephalic version should continue being offered to all eligible patients regardless of prognostic factors for success. PMID- 26667859 TI - Quality of Recovery after Anesthesia: Validation of the Portuguese Version of the 'Quality of Recovery 15' Questionnaire. AB - BACKGROUND: The "Quality of Recovery 15" questionnaire is used for the study of quality recovery after anesthesia. The aim of this study was to validate the Portuguese version of "Quality of Recovery 15" questionnaire. MATERIAL AND METHODS: After study approval by the institutional ethics committee, an observational and cohort prospective study was conducted on patients scheduled for elective surgery from June to August 2013. The "Quality of Recovery 15" questionnaire was translated in accordance with available guidelines. The "Quality of Recovery 15" Portuguese version was used before surgery (T0) and 24h postoperatively (T1) on 170 patients. Patients who were unable to give informed consent or had cognitive impairment were excluded. Poor quality of recovery was defined for "Quality of Recovery 15" score at T1 lower than the mean "Quality of Recovery 15" score minus 1 standard deviation. Reliability and observer disagreement was assessed using interclass correlation. Non-parametric tests were used for comparisons. RESULTS: There was a negative correlation between "Quality of Recovery 15" score and time spent in the postanesthesia care(p = -0.264, p = 0.004) and length of hospital stay (p = -0.274, p = 0.004). Thirty-two patients (19%) had poor quality of recovery. Patients with poor quality of recovery had more frequently diabetes mellitus and hypertension and they were taking antidepressants drugs more frequently. Patients with poor quality of recovery were more frequently submitted to combined anesthesia and less frequently to general anesthesia and locoregional anesthesia (p = 0.008). The questionnaire had a good internal consistency and test-retest reliability was good. DISCUSSION: The Portuguese version of the "Quality of Recovery 15" showed a good correlation with the original. CONCLUSION: This questionnaire appears to be an accurate and reliable assessment for quality of recovery. PMID- 26667858 TI - [The Importance of Early Referral in Pediatric Acute Liver Failure]. AB - INTRODUCTION: Acute liver failure is a rare disorder associated to high morbidity and mortality despite survival improvement through liver transplantation. The importance of a multidisciplinary approach and early referral to a pediatric liver transplantation center were important conclusions of a national meeting in 2008, from which resulted an actuation consensus. OBJECTIVES: To characterize acute liver failure admissions in a Pediatric Intensive Care Unit of the portuguese pediatric livertransplantation center. To compare results before (A) and after (B) 2008. MATERIAL AND METHODS: Observational, retrospective study during a 20 year period (1994-2014). INCLUSION CRITERIA: age < 18 years old and acute liver failure (INR >= 2 without vitamin K response and hepatocellular necrosis). Children with previous liver disease were excluded. RESULTS: Fifty children were included, with median age of 24.5 months. The most common etiology under 2 years old was metabolic (34.6%) and above that age was infectious (29.2%). Forty six percent were submitted to liver transplantation and 78% of them survived. Overall mortality was 34%. Median referral time was 7 days in period A (n = 35) and 2 days in period B (n = 15; p = 0.006). Pediatric risk of mortality's median was 14.7 in period A and 6.5 in B (p = 0.019). Mortality was 37% vs 26% in periods A and B, respectively (p = 0.474). DISCUSSION AND CONCLUSIONS: Overall mortality was similar to the observed in other European centers. Liver transplantation is in fact the most effective therapeutic option. After 2008, there was a reduction in referral time and cases severity on admission; however, mortality has not reduced so far. PMID- 26667860 TI - Translation, Cultural Adaptation and Validation of the Power of Food Scale for Use by Adult Populations in Portugal. AB - INTRODUCTION: The Power of Food Scale measures appetite for, rather than consumption of, palatable foods - a construct frequently designated as hedonic hunger. The purpose of this study was to examine the psychometric properties of a Portuguese version of the Power of Food Scale, namely reliability and construct validity. MATERIAL AND METHODS: Data was obtained from 1266 adult participants sampled from three different populations in Portugal: two nonclinical samples and one multi-center sample of severely obese candidates for weight-loss surgery. RESULTS: We found that the factor structure of the Portuguese version of the Power of Food Scale is similar to that of the original scale and that the Portuguese version of the Power of Food Scale has good internal structure, test retest reliability and construct validity. In addition, we provide the first contribution towards defining population norms for Power of Food Scale scores. DISCUSSION: The Portuguese version of the Power of Food Scale proved to have good psychometric properties: it is a valid and reliable tool for measuring hedonic hunger, supporting its use both in clinical and non-clinical samples, as well as in prospective studies. CONCLUSION: Our results show that the Portuguese version of the Power of Food Scale is a useful measure for researchers and clinicians who are interested in exploring the construct of hedonic hunger in Portuguese speaking populations, including those suffering from obesity. PMID- 26667861 TI - [Streptococcus pneumoniae Vaccination in Children and Adolescents at High Risk of Invasive Pneumococcal Disease]. AB - BACKGROUND: In Portugal, pneumococcal vaccination is free of charge and recommended by the Directorate-General of Health for the pediatric population at high risk of invasive pneumococcal disease. Our main aim was to describe the vaccination uptake in a pediatric population attending a hospital outpatient clinic. MATERIAL AND METHODS: Cross-sectional observational survey of a pediatric population attending a referral hospital outpatient clinic, from July to December 2014. Data was collected from clinical records, Individual Health Bulletin or the registry from Plataforma de Dados da Saude(r). RESULTS: Of the 122 participants, 95.9% had, at least, one shot of pneumococcal vaccine, but only 64.8% of these completed the age recommended vaccination scheme. Uptake was higher in children < 5 years old. The proportion of complete vaccination schemes was 100% in hemoglobinopathies and human immunodeficiency virus infection groups, 66.7% in prematures, 62.5% in splenectomized and 54.7% in Down syndrome. Children had better complete vaccination schemes when they attended the Pediatric Infectious Disease (100%) and Pulmonology Clinics (88.2%). Children > 5 years old had a higher uptake of 23-valent polysaccharide vaccine than the 2 to 5-years old ones (74.5% vs 40.5%; p < 0.001). DISCUSSION: Most of our pediatric population at high risk of IPD was vaccinated; nevertheless, only two-thirds had completed the scheme for their age. The main failure was on the 23-valent polysaccharide vaccine administration. CONCLUSIONS: Although these results are better than those reported in other European countries with similar recommendations, it is essential to explore the causes for the observed flaws in order to optimize vaccination rates. PMID- 26667862 TI - [Characterization and Evolution of Avoidable Admissions in Portugal: The Impact of Two Methodologic Approaches]. AB - INTRODUCTION: The aim of this study is to evaluate the health systems performance through the avoidable hospital admissions, once these have gained international relevance. We used two different methods to identify the admissions for Ambulatory Care Sensitive Conditions, describing the Portuguese reality and evolution. MATERIAL AND METHODS: Over 12 million hospitalizations were analyzed between 2000 and 2012 using the national hospital discharge databases. We used two different methodologies to identify the hospitalizations for Ambulatory Care Sensitive Conditions, determining their concordance. We also estimated potential improvement scenarios. RESULTS: In 2012, 4.4% and 32.4% of the hospitalizations for medical causes were avoidable according to the Canadian and Spanish methodologies respectively. The hospitalizations are more frequent in children and the elderly. The most frequent causes vary according to the age group and methodology. During the analyzed period the rate of admissions has dropped 20% according to the Canadian methodology and increased 16% according to the Spanish methodology. There are regional clusters of performance under and above the national average. The concordance between methodologies is low. The improvement scenarios estimated possible reductions between 20.3% and 53.5% of the hospitalizations. DISCUSSION: The avoidable admissions assume a relevant volume in Portugal. Although in theory they are avoidable their complete elimination is a practical impossibility. Their study, however, allows the evaluation and results motorization enabling to establish intervention priorities. CONCLUSION: To have a precise characterization of the avoidable admissions in Portugal it is necessary to achieve consensus on the identification methodology. PMID- 26667863 TI - [Neonatal Morbidity in Term Newborns Born by Elective Cesarean Section]. AB - INTRODUCTION: International guidelines suggest that non-urgent planned deliveries be scheduled at or after 39 weeks. Despite this recommendation elective cesarean often occurs before 39 weeks. Some research has demonstrated that elective cesarean before 39 weeks poses a greater risk to the infants than at or after 39 weeks. OBJECTIVE: To evaluate neonatal morbidity in term newborns born by elective cesarean section. MATERIAL AND METHODS: Retrospective study of all term elective cesarean sections (scheduled and without labor) performed in level III maternity, in the last 11 years (2003 - 2013). High risk pregnancies were excluded: twins, premature rupture of membranes, preeclampsia, poorly controlled diabetes mellitus, Rh isoimmunization and congenital malformations. Two groups of newborns with gestational age less than 39 weeks and equal or greater than 39 weeks gestational age were compared. RESULTS: In our sample, 45% of elective caesarean sections were performed before 39 weeks. Infants born before 39 weeks were more frequently admitted in neonatal intensive care, odds ratio 2.4 [1.4 - 4.1] p = 0.001, had more respiratory morbidity, odds ratio 2.4 [1.6 - 3.8] p < 0.001, more hyperbilirubinaemia odds ratio 2.3 [1.5 - 3.7] p < 0.001, more hypoglycaemia and/or feeding difficulties odds ratio 1.6 [1.2 - 2.4] p = 0.006, and longer admissions (more than five days), odds ratio 2.0 [1.4 - 3] p < 0.001. DISCUSSION: As in other studies 'early term' had higher respiratory and metabolic morbidity and consequently had a longer hospital stay. CONCLUSION: These findings support recommendations to delay elective cesarean delay until 39 weeks of gestation. PMID- 26667864 TI - [Suicidal Behavior among Portuguese Psychiatry Trainees: Comparison with the European Situation]. AB - INTRODUCTION: The aim of this paper was to assess the prevalence of suicide ideation and attempts in Portuguese psychiatry trainees (adult and child and adolescence), and compare the data with the general population and other European countries. MATERIAL AND METHODS: A structured and anonymous questionnaire was sent by email to 159 portuguese trainees of adult psychiatry and child and adolescence psychiatry with questions about personal history of suicidal ideation and suicide attempts, as well as family history of suicide attempts and completed suicides. This is part of the BoSS Study (Burnout Syndrome Study) performed in 21 countries worldwide. Data was analysed in SPSS v.19. RESULTS: From the inquired population, 62 trainees (40,3%) partially responded, and 46 (29%) were complete responders - these entered the final analysis. There was a ratio of 2:1 (female:male) and a mean age of 29 years. The suicidal ideation was present in passive form in 44% and in active form in 33%; also, 4.3% of respondents had previous suicide attempts. In first degree relatives, 22% had attempted suicide and 13% completed suicide. DISCUSSION: The results are worriying and may be associated with some factors to which this population is exposed. CONCLUSION: It is necessary further research to better understand this phenomenon, its causes and potential modifiers. PMID- 26667865 TI - Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study. AB - INTRODUCTION: It is still unclear whether the etiology of ischemic stroke differs between cancer and non-cancer patients. Stroke and cancer share common modifiable risk factors but evidence suggests that cancer patients have specific conditions that increase the risk of stroke. Our goal was to compare the etiology of ischemic stroke in cancer and non-cancer patients. MATERIAL AND METHODS: Case control study conducted in patients admitted to a stroke unit between January 2007 and December 2012. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls of only stroke. Age, gender, vascular risk factors and etiology were compared between groups. RESULTS: Fifty-six cases were identified; 64.3% were men with a mean age of 71 years; 21 patients had evidence of active cancer. Gastrointestinal cancer (25.9%) was the most common; 151 controls were included matched for gender and age. Common modifiable vascular risk factors, between groups (cases versus controls) were not significantly different, except for diabetes mellitus, more frequent in the control group (16.1% vs 33.8%, p = 0.02). Previous thrombotic events were more frequent in the cancer cohort (8.9% vs 0.7%, p = 0.007). Other determined etiology subtype (TOAST classification) was more frequent in cancer patients when compared to controls (13.0% vs 0.8%, p < 0.01), and a hypercoagulable state was significantly more prevalent in active cancer patients. DISCUSSION: In our case-control study two subsets of cancer patients were delineated. In a subgroup, cancer and stroke co-exist, sharing traditional vascular risk factors. In another subset of patients, stroke appears to be directly related to the presence of a malignancy, where hypercoagulopathy turns out to be a decisive mechanism. CONCLUSION: In clinical grounds, hypercoagulopathy as stroke etiology should prompt the physician to screen the patient for occult cancer. PMID- 26667866 TI - Hyperbaric Oxygen Therapy for the Treatment of Fournier's Gangrene: A Review of 34 Cases. AB - INTRODUCTION: Fournier's gangrene is a serious necrotizing infection that can be fatal if not promptly attended. Treatment for this condition consists of a combination of surgical debridement, antibiotherapy and supportive care. Hyperbaric oxygen therapy is used as an adjuvant for the optimization of infected tissue oxygenation and for its bactericidal and bacteriostatic effects. MATERIAL AND METHODS: The data presented in this study encompass a period of 25 years of clinical records of patients with Fournier's gangrene that had been treated at our center with hyperbaric oxygen therapy. RESULTS: A total of 34 patients were treated. The vast majority of patients were males (94.1%) with a mean age of 53.7 years. Urinary tract was the most frequent source of infection and diabetes was most common comorbidity seen in patients. Mortality rate was 20.8%. DISCUSSION: The most common observed comorbidity was diabetes, suggesting diabetes as one predisposing factor. The majority of deceased patients had diabetes, although no significant correlation between diabetes and death was found. The area of residence of patients may affect patients' referral to these facilities. CONCLUSIONS: Although Fournier's gangrene is a rare condition, it is nevertheless a fatal illness, namely in patients with comorbidities like diabetes. Hyperbaric oxygen therapy is recommended as an adjuvant to conventional therapy and should be considered whenever available. To further assess the role of hyperbaric oxygen therapy, in the treatment of this condition, additional studies should be carried out. PMID- 26667867 TI - [Mediterranean Spotted Fever: Retrospective Review of Hospitalized Cases and Predictive Factors of Severe Disease]. AB - INTRODUCTION: Mediterranean spotted fever, an ancient zoonotic disease raising current issues. This study aims to reevaluate the disease clinical picture and to identify prognostic factors related to severe disease. MATERIAL AND METHODS: We evaluate cases admitted to a central hospital during 12-year period. The risk factors were determined by uni and multivariate analysis, comparing patients admitted in general infirmary versus intermediate/intensive care units or in case of death. RESULTS: We reviewed 71 cases of Mediterranean spotted fever. The mean age was 63.3 +/- 16.7 years and 52.1% were male. The eschar was observed in 62.0%. Fever and rash were the most common clinical findings. Forty five percent of patients developed complications and 22.5% were admitted to intermediate and/or intensive care units. Apyrexia, dyspnea, renal failure and elevated lactic dehydrogenase levels at admission were predictors of severe disease development (p < 0.034). Alcoholism was related with prolonged hospitalization (p = 0.020). Absence of fever (p = 0.019) and elevated serum creatinine levels (p = 0.028) were identified as independent factors associated with severe outcome. The mortality rate was 2.8%. DISCUSSION: Although Mediterranean spotted fever is usually assumed to be benign, severe cases are emerging. CONCLUSION: Early identification of the infection and continuous patient surveillance are crucial, particularly in those with greater risk of developing severe or fatal disease. PMID- 26667868 TI - Current Clinical Indications for Small Bowel Capsule Endoscopy. AB - INTRODUCTION: Small bowel capsule endoscopy is currently the first line diagnostic examination for many diseases affecting the small bowel. This article aims to review and critically address the current indications of small bowel capsule endoscopy in clinical practice. MATERIAL AND METHODS: Bibliographic review of relevant and recent papers indexed in PubMed. RESULTS AND DISCUSSION: Small bowel capsule endoscopy enables a non-invasive full-assessment of the small bowel mucosa, with high diagnostic yield even for subtle lesions. In patients with obscure gastrointestinal bleeding, diagnostic yield is higher when performed early after the onset of bleeding. Endoscopic treatment of angioectasias using balloon-assisted enteroscopy may contribute to reduce rebleeding, while the risk of rebleeding in patients with 'negative' small bowel capsule endoscopy is debatable. Cross-sectional imaging may be more accurate than small bowel capsule endoscopy for the diagnosis of large small bowel tumors. The Smooth Protruding Index on Capsule Endoscopy (SPICE score) may help to differentiate submucosal tumors from innocent bulges. Small bowel capsule endoscopy is also a key diagnostic instrument in patients with suspected Crohn's disease and non diagnostic ileocolonoscopy; it may also influence prognosis and therapeutic management, by determining disease extent and activity in patients with known Crohn's disease. The role of small bowel capsule endoscopy to investigate possible complications in patients with non-responsive coeliac disease is evolving. CONCLUSIONS: Small bowel capsule endoscopy is a valuable diagnostic instrument for patients with obscure gastrointestinal bleeding and/or suspected small bowel tumors; it may also be a key examination in patients with suspected Crohn's disease, or patients with known Crohn's disease to fully assess disease extension and activity; finally, it may contribute for the diagnosis of complications of non-responsive coeliac disease. PMID- 26667869 TI - Monoclonal Antibodies for Multiple Sclerosis Treatment. AB - Since their introduction in medical therapy, in the last quarter of the 20th century, monoclonal antibodies have gained an increasing importance in the treatment of various diseases. Neurology has been one of the medical specialties benefiting of the therapeutic potential of these monoclonal antibodies and certain neurological conditions may now contain such drugs in their therapeutic algorithms. Multiple sclerosis is one of these diseases and, in addition to the monoclonal antibodies already licensed for clinical use, several others are in development for future utilization in this specific area. The future will certainly pass through this kind of drugs and, in this article, a review of the most relevant data related to monoclonal antibodies already in use and also in clinical development for multiple sclerosis treatment will be performed. PMID- 26667870 TI - [Periarticular Corticosteroid Injection in the Therapeutic Approach of Musculoskeletal Disease in General Practice: A systematic Review]. AB - INTRODUCTION: Periarticular corticosteroid injection utilization by General Practitioners treating musculoskeletal disease in primary health care system is internationally acknowledged. This article aims at analyzing this evidence and contributing to the discussion of a potential development of the technique in Portugal. MATERIAL AND METHODS: Qualitative analysis of randomized control trials, cost-effectiveness studies, cross-sectional studies, retrospective cohort studies and observational studies, using PRISMA model. DATA SOURCES: PubMed, Cochrane Library and Essential Evidence Plus. ELIGIBILITY CRITERIA: corticosteroid injection mention in the treatment of musculoskeletal disease and an element that indicates primary health care context. RESULTS: Nine randomized control trials, three cost-effectiveness studies, three cross-sectional studies, three descriptive studies and one retrospective cohort study were reviewed. Most success parameters of corticosteroid injections performed by general practitioners showed short term efficacy; at long term they did not outstand other therapeutic options. The balance between the economic burden ascribed to this technique utilization in primary health care context and gain in subject's quality of life is favorable. The eleven studies assessing security registered only minor side effects and no serious ones. DISCUSSION: The periarticular corticosteroid injection technique performance places it as a therapeutic option treating musculoskeletal disease in Portuguese primary health care. Nevertheless further evidence is required to support its efficacy and safety parameters, namely at national level. CONCLUSION: Corticosteroid injection utilization in primary health care constitutes an effective and safe option, with the potential to improve primary health care service rendering in an economically sustainable way. PMID- 26667871 TI - [Hypothyroidism Associated to TSH Hormone-Receptor Autoantibodies with Blocking Activity Assessed In Vitro]. AB - Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient's serum; it was estimated a 'moderate' blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis. PMID- 26667873 TI - [Takotsubo Cardiomyopathy: Cause of a Cardiogenic Shock]. AB - Takotsubo cardiomyopathy, of unknown etiology, is characterized by sudden and transient systolic dysfunction of the mid-apical segments of the left ventricle without significant coronary disease, and full normalization of segmental changes. More common in middle-aged women, it is cause of differential diagnosis with acute coronary syndrome. We present the case of a 59 year old woman admitted to the emergency room with sudden chest pain and dyspnea. At presentation: acute hypotensive pulmonary edema requiring aminergic support and invasive ventilation. Blood tests showed elevated necrosis myocardial enzymes. Serial electrocardiograms: sinus rhythm with progressive inversion of the T wave through the precordial leads (v2 - v6). Control echocardiograms: overall decreased systolic function with apical akinesia, and full reversal of the changes in 2 weeks. Cardiogenic shock of unknown etiology was admitted and a coronary computed tomography angiography was performed excluding coronary heart disease, supporting the diagnosis of Takotsubo cardiomyopathy. PMID- 26667872 TI - [Auto-Immune Pancreatitis: The Diagnostic Role of Imaging Studies]. AB - Auto-immune pancreatitis is an uncommon and underdiagnosed pathology. Its clinical picture is not specific and the diagnosis is therefore difficult. Imaging studies have a crucial role in the diagnostic process and also in the follow-up of treatment. With the objective of emphasizing the importance of imaging in the correct diagnosis of this pathology, the authors report the case of a patient with longterm unspecific abdominal complaints that was diagnosed as auto-immune pancreatitis after laboratorial and imaging investigation. Assuming this diagnosis it was instituted treatment with oral methylprednisolone, which succeeded, with progressive resolution of the clinical, laboratorial and imaging findings. PMID- 26667874 TI - Pantothenate Kinase Associated Neurodegeneration in Two Brothers. PMID- 26667875 TI - Haemorrhagic Gingival Hypertrophy: A Striking Presentation of Acute Myelomonocytic Leukaemia. PMID- 26667876 TI - Alcohol and Youth in Portugal: An Intervention Through the Triangle Project. PMID- 26667877 TI - [Thirdhand Smoke: A Concept to Remember!]. PMID- 26667878 TI - Habitat availability and gene flow influence diverging local population trajectories under scenarios of climate change: a place-based approach. AB - Ecological niche theory holds that species distributions are shaped by a large and complex suite of interacting factors. Species distribution models (SDMs) are increasingly used to describe species' niches and predict the effects of future environmental change, including climate change. Currently, SDMs often fail to capture the complexity of species' niches, resulting in predictions that are generally limited to climate-occupancy interactions. Here, we explore the potential impact of climate change on the American pika using a replicated place based approach that incorporates climate, gene flow, habitat configuration, and microhabitat complexity into SDMs. Using contemporary presence-absence data from occupancy surveys, genetic data to infer connectivity between habitat patches, and 21 environmental niche variables, we built separate SDMs for pika populations inhabiting eight US National Park Service units representing the habitat and climatic breadth of the species across the western United States. We then predicted occurrence probability under current (1981-2010) and three future time periods (out to 2100). Occurrence probabilities and the relative importance of predictor variables varied widely among study areas, revealing important local scale differences in the realized niche of the American pika. This variation resulted in diverse and - in some cases - highly divergent future potential occupancy patterns for pikas, ranging from complete extirpation in some study areas to stable occupancy patterns in others. Habitat composition and connectivity, which are rarely incorporated in SDM projections, were influential in predicting pika occupancy in all study areas and frequently outranked climate variables. Our findings illustrate the importance of a place-based approach to species distribution modeling that includes fine-scale factors when assessing current and future climate impacts on species' distributions, especially when predictions are intended to manage and conserve species of concern within individual protected areas. PMID- 26667879 TI - Powdered coconut water as a storage medium to preserve the viability of periodontal ligament cells: a laboratory study. AB - AIM: To investigate the ability of newly developed powdered coconut water formulas (ACP) with different osmolarities to maintain the viability of periodontal ligament (PDL) cells over time compared with other solutions. METHODOLOGY: Dogs teeth were extracted and stored for two periods, 3 h or 24 h, in the following media: long-shelf life CW (CW), pH-adjusted long-shelf life CW (pH-CW) and powdered CW that was pH and osmolality adjusted (ACP-404-I, 250 mOsm kg-1 H2 O; pH 7.0; ACP-404-II, 372 mOsm kg-1 H2 O; pH 7.0; ACP-404-III, 300 mOsm kg-1 H2 O; pH 7.4). The positive control group (Pc) corresponded to immediate measurement after tooth extraction, and two negative controls (Nc) corresponded to 3 h and 24 h of dry time. PDL cells were extracted, and cell viability analysed by Trypan blue exclusion. Data were analysed statistically using two-way anova followed by the Tukey test and one-way anova followed by the Dunnett test (P < 0.05). RESULTS: At 3 h and 24 h, ACP-404-I had a performance similar to those of ACP-404-II and pH-CW, with significantly higher (P = 0.004) percentages of viable cells than ACP-404-III and CW. The positive control group had a significantly higher (P = 0.002) percentage of viable cells than the negative control groups, CW and ACP-404-III, irrespective of the period evaluated. CONCLUSION: Powdered coconut water formulas, ACP-404-I and ACP-404-II, preserved viability for up to 24 h. PMID- 26667880 TI - Living With a Contested, Stigmatized Illness: Experiences of Managing Relationships Among Women With Fibromyalgia. AB - This study focuses on the negotiation of relationships among women living with the chronic illness fibromyalgia. Twenty in-depth, semistructured interviews were conducted with women diagnosed with fibromyalgia. Drawing from interactional and constructionist perspectives, the analysis focuses on participants' approaches to communicating with others about their illness, the reactions of others to their experiences, and participants' strategies to manage stigma. Participants attempted to describe their illness experience to others through direct and educational approaches. Often, in the management of their relationships with close family and friends, there was an unspoken awareness of illness effects, and social support was offered. However, disbelief and a lack of understanding often led participants to avoid social interactions in the attempt to hide from the stigma associated with an invisible and contested illness. PMID- 26667881 TI - Meta-Study as Diagnostic: Toward Content Over Form in Qualitative Synthesis. AB - Having previously conducted qualitative syntheses of the diabetes literature, we wanted to explore the changes in theoretical approaches, methodological practices, and the construction of substantive knowledge which have recently been presented in the qualitative diabetes literature. The aim of this research was to explore the feasibility of synthesizing existing qualitative syntheses of patient perspectives of diabetes using meta-study methodology. A systematic review of qualitative literature, published between 2000 and 2013, was conducted. Six articles were identified as qualitative syntheses. The meta-study methodology was used to compare the theoretical, methodological, analytic, and synthetic processes across the six studies, exploring the potential for an overarching synthesis. We identified that while research questions have increasingly concentrated on specific aspects of diabetes, the focus on systematic review processes has led to the neglect of qualitative theory and methods. This can inhibit the production of compelling results with meaningful clinical applications. Although unable to produce a synthesis of syntheses, we recommend that researchers who conduct qualitative syntheses pay equal attention to qualitative traditions and systematic review processes, to produce research products that are both credible and applicable. PMID- 26667882 TI - Through Their Eyes: Lessons Learned Using Participatory Methods in Health Care Quality Improvement Projects. AB - In this methodological article, we examine participatory methods in depth to demonstrate how these methods can be adopted for quality improvement (QI) projects in health care. We draw on existing literature and our QI initiatives in the Department of Veterans Affairs to discuss the application of photovoice and guided tours in QI efforts. We highlight lessons learned and several benefits of using participatory methods in this area. Using participatory methods, evaluators can engage patients, providers, and other stakeholders as partners to enhance care. Participant involvement helps yield actionable data that can be translated into improved care practices. Use of these methods also helps generate key insights to inform improvements that truly resonate with stakeholders. Using participatory methods is a valuable strategy to harness participant engagement and drive improvements that address individual needs. In applying these innovative methodologies, evaluators can transcend traditional approaches to uniquely support evaluations and improvements in health care. PMID- 26667883 TI - Cell-free Epstein-Barr virus-DNA in patients with nasopharyngeal carcinoma: Plasma versus urine. AB - BACKGROUND: The purpose of this study was to explore urinary Epstein-Barr virus (EBV)-DNA as a potential biomarker in patients with nasopharyngeal carcinoma (NPC). METHODS: EBV-DNA copies were estimated in plasma/urine of patients with NPC (n = 76) by real-time polymerase chain reaction (PCR) at baseline, during therapy, and at follow-up. Their correlation with EBV-RNA expression in tissues (n = 53) was used to assess sensitivity and specificity of plasma/urine EBV-DNA. Correlation of urine and plasma EBV-DNA with each other and with radiological response was evaluated. RESULTS: This study demonstrated that urine EBV-DNA has high sensitivity (96%) at diagnosis and it correlates well with plasma EBV-DNA at baseline and after neoadjuvant chemotherapy. The EBV-DNA copies reduced significantly with therapy (plasma: p < .001; urine: p = .011). Patients with low EBV-DNA copies demonstrated improved survival (plasma: p = .023; urine: p = .083). CONCLUSION: Plasma EBV-DNA is a good prognostic marker, whereas further study on a larger cohort may help in developing urine EBV-DNA as a surrogate prognostic marker for patients with NPC. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1666-E1673, 2016. PMID- 26667884 TI - Fine-tuning by strigolactones of root response to low phosphate. AB - Strigolactones are plant hormones that regulate the development of different plant parts. In the shoot, they regulate axillary bud outgrowth and in the root, root architecture and root-hair length and density. Strigolactones are also involved with communication in the rhizosphere, including enhancement of hyphal branching of arbuscular mycorrhizal fungi. Here we present the role and activity of strigolactones under conditions of phosphate deprivation. Under these conditions, their levels of biosynthesis and exudation increase, leading to changes in shoot and root development. At least for the latter, these changes are likely to be associated with alterations in auxin transport and sensitivity. On the other hand, strigolactones may positively affect plant-mycorrhiza interactions and thereby promote phosphate acquisition by the plant. Strigolactones may be a way for plants to fine-tune their growth pattern under phosphate deprivation. PMID- 26667885 TI - The Evolving Scale and Profile of Cancer Worldwide: Much Ado About Everything. AB - Today, cancer is responsible for one in three premature deaths from noncommunicable diseases worldwide, and the number of annual cancer diagnoses will rise to well over 20 million by the year 2030. That cancer is of profound importance to future global health reflects both recent gains in human development as well as mortality transitions that are centuries old. Still, cancer is complex, and the extensive geographical and temporal heterogeneity alerts us to the need for targeted, local approaches to cancer control. The study of trends in specific cancer types remains essential in monitoring and evaluating such strategies and as a descriptive tool for hypothesizing possible contributory factors. Of greatest necessity is an expansion of the availability of high quality data. To improve the limited cancer incidence data available in low- and middle-income countries (LMIC), the Global Initiative for Cancer Registry Development (http://gicr.iarc.fr) is an international partnership supporting countries to redraw the surveillance map. PMID- 26667886 TI - Global Cancer Incidence and Mortality Rates and Trends--An Update. AB - There are limited published data on recent cancer incidence and mortality trends worldwide. We used the International Agency for Research on Cancer's CANCERMondial clearinghouse to present age-standardized cancer incidence and death rates for 2003-2007. We also present trends in incidence through 2007 and mortality through 2012 for select countries from five continents. High-income countries (HIC) continue to have the highest incidence rates for all sites, as well as for lung, colorectal, breast, and prostate cancer, although some low- and middle-income countries (LMIC) now count among those with the highest rates. Mortality rates from these cancers are declining in many HICs while they are increasing in LMICs. LMICs have the highest rates of stomach, liver, esophageal, and cervical cancer. Although rates remain high in HICs, they are plateauing or decreasing for the most common cancers due to decreases in known risk factors, screening and early detection, and improved treatment (mortality only). In contrast, rates in several LMICs are increasing for these cancers due to increases in smoking, excess body weight, and physical inactivity. LMICs also have a disproportionate burden of infection-related cancers. Applied cancer control measures are needed to reduce rates in HICs and arrest the growing burden in LMICs. PMID- 26667887 TI - Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol Binding Protein 4 Gene. AB - BACKGROUND/AIMS: Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. METHODS: This was a cross sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their RBP4 variant. RESULTS: Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the RBP4 variant. The T allele promoted adiposity-reducing effects of vitamin A in VF and adiposity-enhancing effects in SF, while the C allele had adiposity-reducing effects in both VF and SF. CONCLUSIONS: Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity. PMID- 26667890 TI - Animal medical genetics: a perspective on the epidemiology and control of inherited disorders. AB - This perspective considers genetic disorders of domestic animal populations, in particular their epidemiology and control. Inherited disorders of animals share the same basic molecular biology as those of human beings, but they differ in their epidemiology due largely to the breed structure of the various species, human control of breeding and a greater influence of the founder effect, particularly due to extensive use of a limited number of sires, and inbreeding. Control of genetic disorders in animals is also more practical through extensive screening for disease, or heterozygous animals within defined breed populations, followed by exclusion of affected or carrier animals from breeding. This is assisted by the fact that, within a breed, many inherited monogenic disorders are associated with a single mutation. However some of the more important disorders may be inherited in a non-Mendelian manner, being influenced by multiple genes as well as environmental factors. These aspects are discussed and contrasted with similar aspects in human medical genetics. PMID- 26667889 TI - The interactive effects of age, education, and BMI on cognitive functioning. AB - We examined the moderating effects of age and cognitive reserve on the relationship between body mass index (BMI) and processing speed, executive function, and working memory based on the literature suggesting that obese individuals perform more poorly on measures of these abilities. Fifty-six healthy, dementia-free community-dwelling older (mean age 65.72 +/- 7.40) and younger (mean age 21.10 +/- 2.33) adults completed a neuropsychological battery and reported height and weight. Mixed effects models were used to evaluate the interactive effects of age, education (a proxy for cognitive reserve), and BMI on cognitive scores. Higher education was protective for executive deficits in younger, but not older adults. Age differences in executive functions were reduced at higher education levels but increased in individuals with higher BMI. Results suggest the inter-relationships between cognitive reserve - as measured by education - and BMI differ across age, and that obesity may accelerate the cognitive aging process. PMID- 26667888 TI - Perspectives on the Tertiary Prevention Strategy for Alzheimer's Disease. AB - Amyloid-beta (Abeta) plays a pivotal role in Alzheimer's disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Abeta-targeting clinical trials, however, has prompted questions on whether Abeta is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Abeta, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Abeta alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Abeta and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD. PMID- 26667891 TI - Status of Vitamin B12 and Folate among the Urban Adult Population in South India. AB - BACKGROUND: Deficiency of vitamin B12 (B12) and folate (FA) leads to a wide spectrum of disorders that affect all age groups. However, reports on B12 and FA status in healthy adults in India are limited. Hence, we determined the plasma levels and dietary intake of B12 and FA in the adult population. METHODS: We conducted a community-based cross-sectional study in an urban setup among 630 apparently healthy adults distributed into 3 age groups: 21-40, 41-60 and >60 years. Plasma concentrations of B12 and FA were analyzed by radio immunoassay and dietary intake by 24-hour recall method. RESULTS: The overall prevalence of FA deficiency was 12%, but there was no significant difference in plasma FA concentrations among the groups. While the overall prevalence of B12 deficiency was 35%, it was significantly higher in the 21-40 (44%) and 41-60 age groups (40%) when compared with the >60 group (30%). B12 deficiency was higher in vegetarians (54%) compared to those consuming mixed diet (31%), and the reverse was the case with FA. However, the dietary intakes of FA and B12 were not significantly different among the groups. CONCLUSIONS: These results indicate a higher prevalence of B12 deficiency in apparently healthy adults in an urban setup. PMID- 26667892 TI - Importance of Relationship between Ductus and Isthmus in Fetal Diagnosis of Coarctation of Aorta. AB - BACKGROUND: The prenatal diagnosis of coarctation of aorta (CoA) can prove problematic, with relatively high false-positive and false-negative rates. This significantly impacts both prenatal counseling and postnatal management. We sought to evaluate a variety of prenatal echo indices to determine which would best predict neonatal CoA. METHODS: Fetal echocardiograms of those with prenatal diagnosis of COA were analyzed for the following: diameter of cardiac valves, ascending aorta, distal transverse arch, aortic isthmus, and ductus; right (RV) and left ventricular (LV) length and end-diastolic area and isthmus-ductal angle (IDA). Ratios of RV: LV area, aortic: pulmonary valve diameter, mitral: tricuspid valve ratio (MV:TV ratio), and isthmus: ductal diameter (IDD) were calculated. These measures were compared between those with CoA after birth (CoA group) and those without (no CoA group). RESULTS: Of the 62 subjects, 27 were in CoA and 35 in no CoA group. CoA group had a significantly smaller mitral valve, MV:TV ratio, IDD, and IDA compared to no CoA group. The ROC curves for each of these significant measures showed that mitral valve, IDD, and IDA had an AUC of 0.72, 0.80, and 0.83, respectively. Multiple variable model using at least two of these measures had 85% sensitivity and 60% specificity. CONCLUSIONS: A smaller mitral valve, MV:TV ratio, IDD, and IDA are associated with development of neonatal coarctation. In cases with suspected prenatal diagnosis of CoA, careful evaluation of the relation between the isthmus and the ductus arteriosus using IDD and IDA may enhance the diagnostic accuracy of fetal echocardiograms. PMID- 26667893 TI - Coherent controlization using superconducting qubits. AB - Coherent controlization, i.e., coherent conditioning of arbitrary single- or multi-qubit operations on the state of one or more control qubits, is an important ingredient for the flexible implementation of many algorithms in quantum computation. This is of particular significance when certain subroutines are changing over time or when they are frequently modified, such as in decision making algorithms for learning agents. We propose a scheme to realize coherent controlization for any number of superconducting qubits coupled to a microwave resonator. For two and three qubits, we present an explicit construction that is of high relevance for quantum learning agents. We demonstrate the feasibility of our proposal, taking into account loss, dephasing, and the cavity self-Kerr effect. PMID- 26667894 TI - Transcriptional regulation of insect steroid hormone biosynthesis and its role in controlling timing of molting and metamorphosis. AB - The developmental transition from juvenile to adult is often accompanied by many systemic changes in morphology, metabolism, and reproduction. Curiously, both mammalian puberty and insect metamorphosis are triggered by a pulse of steroid hormones, which can harmonize gene expression profiles in the body and thus orchestrate drastic biological changes. However, understanding of how the timing of steroid hormone biosynthesis is regulated at the molecular level is poor. The principal insect steroid hormone, ecdysteroid, is biosynthesized from dietary cholesterol in the specialized endocrine organ called the prothoracic gland. The periodic pulses of ecdysteroid titers determine the timing of molting and metamorphosis. To date, at least nine families of ecdysteroidogenic enzyme genes have been identified. Expression levels of these genes correlate well with ecdysteroid titers, indicating that the transcriptional regulatory network plays a critical role in regulating the ecdysteroid biosynthesis pathway. In this article, we summarize the transcriptional regulation of ecdysteroid biosynthesis. We first describe the development of prothoracic gland cells during Drosophila embryogenesis, and then provide an overview of the transcription factors that act in ecdysteroid biosynthesis and signaling. We also discuss the external signaling pathways that target these transcriptional regulators. Furthermore, we describe conserved and/or diverse aspects of steroid hormone biosynthesis in insect species as well as vertebrates. PMID- 26667895 TI - Magnetic Nanoparticles PCR Enzyme-Linked Gene Assay for Quantitative Detection of BCR/ABL Fusion Gene in Chronic Myelogenous Leukemia. AB - BACKGROUND: Magnetic nanoparticles (MNPs) have been widely used in medical diagnostic research. In this work, two technologies, MNPs and polymerase chain reaction (PCR), were combined to increase detection sensitivity and specificity. A novel technique based on the MNPs-PCR enzyme-linked gene assay (MELGA) was developed for detection of the BCR/ABL abnormal gene in chronic myelogenous leukemia (CML) patients. METHODS: An MNPs-labeled BCR forward primer and a biotin labeled ABL reverse primer were used to specifically amplify the target gene. After magnetic separation, the PCR product bound to MNPs labeled with streptavidin-conjugated horseradish peroxidase was incubated with the peroxidase substrate and hydrogen peroxide to generate the colorimetric signal. RESULTS: When compared with real-time quantitative-PCR (RQ-PCR), the MELGA technique exhibited an increased sensitivity of <1 fg with high specificity for the BCR/ABL fusion gene in CML patients. In addition, MELGA colorimetric results correlated well with the number of copies obtained from RQ-PCR. CONCLUSION: This simple and cost-effective technique is suitable for monitoring CML patients during targeted therapy (tyrosine kinase inhibitors) especially in rural hospitals. PMID- 26667896 TI - Space occupation near the basket shapes collective behaviours in youth basketball. AB - This study aimed to analyse how youth basketball players explored numerical overloads during shot attempts by measuring their space occupation across specific court areas. Four process-tracing variables measured how the number of attackers (NA), number of defenders (ND), interpersonal distance between attacker and the closest defender (ID) and distance between attacker and the basket (DBkt) impacted on the performance outcome (converted shot; missed shot; ball possession lost). Ten competitive games involving 13 U14 teams were video recorded and players' displacements were digitised. The associations between performance outcomes and the process-tracing measures were assessed using standardised mean differences and a cross-correlation function. A multinomial logistic regression was used to calculate the odds ratio (OR) for each of the three possible outcomes. Results revealed that when shot attempts occurred at larger ID and at smaller DBkt, the possibilities to obtain a converted shot increased. The numerical overload of defenders near the scoring target was predominantly associated with offensive success. Also, the possibility of attackers to lead the spatial relation of movements with the defenders, near the scoring target, appeared as a prominent strategy to succeed. In sum, basketball teams that exhibit potential to adapt their collective behaviours to local changes in the environment might be closer to achieving successful outcomes. PMID- 26667897 TI - What are the indications for the use of computed tomography before septoplasty? PMID- 26667900 TI - Acute anorexigenic action of leptin in rainbow trout is mediated by the hypothalamic Pi3k pathway. AB - Leptin (Lep) is an anorexigenic hormone and regulates appetite-related neuropeptides in mammals. A number of neuropeptides have also been linked to appetite regulation in teleost fish, but Lep signaling activation and effects on appetite-regulating neurons are poorly elucidated in early vertebrates. This study uses cellular, tissue and organismal approaches to elucidate the acute, central Lep action in rainbow trout. The results demonstrate that Lep activates phosphorylation of protein kinase B (Akt) and signal transducer and activator of transcription 3 in rainbow trout hypothalamus-derived cells, and that the phosphatidylinositol-3-kinase (Pi3k) inhibitor LY294002 can suppress the Lep induced Akt phosphorylation. Intracerebroventricular (ICV) Lep administration strongly suppresses food intake at the doses of 0.05 and 0.5 ug Lep fish(-1) At low dose, Lep stimulates hypothalamic transcription of anorexigenic cocaine- and amphetamine-regulated transcript (Cart) and orexigenic neuropeptide Y. At high dose, Lep stimulates hypothalamic transcription of anorexigenic proopiomelanocortin (Pomc) A1, A2, and B, while coinjection with LY294002 reverses this upregulation. The data suggest that the anorexigenic action of Lep in rainbow trout is mediated through stimulation of the anorexigenic neuropeptides Pomc and Cart. Furthermore, ICV Lep treatment increases phosphor Akt-immunoreactive cells in the nucleus lateralis tuberis, periventricular zone along infundibulum, and lateral recess surrounded by nucleus anterior tuberis, while LY294002 inhibits this effect. Lep receptor-immunoreactive cells are also predominant in these regions. These results demonstrate that Lep activates the Pi3k-Akt pathway in the lateral tuberal hypothalamus of rainbow trout for acute appetite regulation, indicating the conservation of anorexigenic Lep action in the mediobasal hypothalamus. PMID- 26667898 TI - Annexin A1 Deficiency does not Affect Myofiber Repair but Delays Regeneration of Injured Muscles. AB - Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1-/-). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1-/- myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma. PMID- 26667899 TI - 60 YEARS OF POMC: From POMC and alpha-MSH to PAM, molecular oxygen, copper, and vitamin C. AB - A critical role for peptide C-terminal amidation was apparent when the first bioactive peptides were identified. The conversion of POMC into adrenocorticotropic hormone and then into alpha-melanocyte-stimulating hormone, an amidated peptide, provided a model system for identifying the amidating enzyme. Peptidylglycine alpha-amidating monooxygenase (PAM), the only enzyme that catalyzes this modification, is essential; mice lacking PAM survive only until mid-gestation. Purification and cloning led to the discovery that the amidation of peptidylglycine substrates proceeds in two steps: peptidylglycine alpha hydroxylating monooxygenase catalyzes the copper- and ascorbate-dependent alpha hydroxylation of the peptidylglycine substrate; peptidyl-alpha-hydroxyglycine alpha-amidating lyase cleaves the N-C bond, producing amidated product and glyoxylate. Both enzymes are contained in the luminal domain of PAM, a type 1 integral membrane protein. The structures of both catalytic cores have been determined, revealing how they interact with metals, molecular oxygen, and substrate to catalyze both reactions. Although not essential for activity, the intrinsically disordered cytosolic domain is essential for PAM trafficking. A phylogenetic survey led to the identification of bifunctional membrane PAM in Chlamydomonas, a unicellular eukaryote. Accumulating evidence points to a role for PAM in copper homeostasis and in retrograde signaling from the lumen of the secretory pathway to the nucleus. The discovery of PAM in cilia, cellular antennae that sense and respond to environmental stimuli, suggests that much remains to be learned about this ancient protein. PMID- 26667901 TI - Validity of near-infrared interactance (FUTREX 6100/XL) for estimating body fat percentage in elite rowers. AB - This investigation aimed to compare hydrostatic weighing (HW) with near-infrared interactance (NIR) and skinfold measurements (SKF) in estimating body fat percentage (FAT%) in rowing athletes. FAT% was estimated in 20 elite male rowers (mean +/- SD: age = 24.8 +/- 2.2 years, height = 191.0 +/- 6.8 cm, weight = 86.8 +/- 11.3 kg, HW FAT% = 11.50 +/- 3.16%) using HW with residual volume, 3-site SKF and NIR on the biceps brachii. Predicted FAT% values for NIR and SKF were validated against the criterion method of HW. Constant error was not significant for NIR (-0.06, P = 0.955) or SKF (-0.20, P = 0.813). Neither NIR (r = 0.045) nor SKF (r = 0.229) demonstrated significant validity coefficients when compared to HW. The standard error of the estimate values for NIR and SKF were both less than 3.5%, while total error was 4.34% and 3.60%, respectively. When compared to HW, SKF and NIR provide similar mean values when compared to HW, but the lack of apparent relationships between individual values and borderline unacceptable total error may limit their application in this population. PMID- 26667904 TI - A decade of progress in observing and modelling Antarctic subglacial water systems. AB - In the decade since the discovery of active Antarctic subglacial water systems by detection of subtle surface displacements, much progress has been made in our understanding of these dynamic systems. Here, we present some of the key results of observations derived from ICESat laser altimetry, CryoSat-2 radar altimetry, Operation IceBridge airborne laser altimetry, satellite image differencing and ground-based continuous Global Positioning System (GPS) experiments deployed in hydrologically active regions. These observations provide us with an increased understanding of various lake systems in Antarctica: Whillans/Mercer Ice Streams, Crane Glacier, Recovery Ice Stream, Byrd Glacier and eastern Wilkes Land. In several cases, subglacial water systems are shown to control ice flux through the glacier system. For some lake systems, we have been able to construct more than a decade of continuous lake activity, revealing internal variability on time scales ranging from days to years. This variability indicates that continuous, accurate time series of altimetry data are critical to understanding these systems. On Whillans Ice Stream, our results from a 5-year continuous GPS record demonstrate that subglacial lake flood events significantly change the regional ice dynamics. We also show how models for subglacial water flow have evolved since the availability of observations of lake volume change, from regional-scale models of water routeing to process models of channels carved into the subglacial sediment instead of the overlying ice. We show that progress in understanding the processes governing lake drainage now allows us to create simulated lake volume time series that reproduce time series from satellite observations. This transformational decade in Antarctic subglacial water research has moved us significantly closer to understanding the processes of water transfer sufficiently for inclusion in continental-scale ice-sheet models. PMID- 26667905 TI - Microbiology of the subglacial Lake Vostok: first results of borehole-frozen lake water analysis and prospects for searching for lake inhabitants. AB - This article examines the question of the possible existence of microbial life inhabiting the subglacial Lake Vostok buried beneath a 4 km thick Antarctic ice sheet. It represents the results of analysis of the only available frozen lake water samples obtained upon the first lake entry and subsequent re-coring the water frozen within the borehole. For comparison, results obtained by earlier molecular microbiological studies of accretion ice are included in this study, with the focus on thermophiles and an unknown bacterial phylotype. A description of two Lake Vostok penetrations is presented for the first time from the point of view of possible clean water sampling. Finally, the results of current studies of Lake Vostok frozen water samples are presented, with the focus on the discovery of another unknown bacterial phylotype w123-10 distantly related to the above mentioned unknown phylotype AF532061 detected in Vostok accretion ice, both successfully passing all possible controls for contamination. The use of clean room facilities and the establishment of a contaminant library are considered to be prerequisites for research on microorganisms from Lake Vostok. It seems that not yet recorded microbial life could exist within the Lake Vostok water body. In conclusion, the prospects for searching for lake inhabitants are expressed with the intention to sample the lake water as cleanly as possible in order to make sure that further results will be robust. PMID- 26667906 TI - Microbiology: lessons from a first attempt at Lake Ellsworth. AB - During the attempt to directly access, measure and sample Subglacial Lake Ellsworth in 2012-2013, we conducted microbiological analyses of the drilling equipment, scientific instrumentation, field camp and natural surroundings. From these studies, a number of lessons can be learned about the cleanliness of deep Antarctic subglacial lake access leading to, in particular, knowledge of the limitations of some of the most basic relevant microbiological principles. Here, we focus on five of the core challenges faced and describe how cleanliness and sterilization were implemented in the field. In the light of our field experiences, we consider how effective these actions were, and what can be learnt for future subglacial exploration missions. The five areas covered are: (i) field camp environment and activities, (ii) the engineering processes surrounding the hot water drilling, (iii) sample handling, including recovery, stability and preservation, (iv) clean access methodologies and removal of sample material, and (v) the biodiversity and distribution of bacteria around the Antarctic. Comparisons are made between the microbiology of the Lake Ellsworth field site and other Antarctic systems, including the lakes on Signy Island, and on the Antarctic Peninsula at Lake Hodgson. Ongoing research to better define and characterize the behaviour of natural and introduced microbial populations in response to deep-ice drilling is also discussed. We recommend that future access programmes: (i) assess each specific local environment in enhanced detail due to the potential for local contamination, (ii) consider the sterility of the access in more detail, specifically focusing on single cell colonization and the introduction of new species through contamination of pre-existing microbial communities, (iii) consider experimental bias in methodological approaches, (iv) undertake in situ biodiversity detection to mitigate risk of non-sample return and post-sample contamination, and (v) address the critical question of how important these microbes are in the functioning of Antarctic ecosystems. PMID- 26667907 TI - Physical and chemical controls on habitats for life in the deep subsurface beneath continents and ice. AB - The distribution of life in the continental subsurface is likely controlled by a range of physical and chemical factors. The fundamental requirements are for space to live, carbon for biomass and energy for metabolic activity. These are inter-related, such that adequate permeability is required to maintain a supply of nutrients, and facies interfaces invite colonization by juxtaposing porous habitats with nutrient-rich mudrocks. Viable communities extend to several kilometres depth, diminishing downwards with decreasing porosity. Carbon is contributed by recycling of organic matter originally fixed by photosynthesis, and chemoautotrophy using crustal carbon dioxide and methane. In the shallow crust, the recycled component predominates, as processed kerogen or hydrocarbons, but abiotic carbon sources may be significant in deeper, metamorphosed crust. Hydrogen to fuel chemosynthesis is available from radiolysis, mechanical deformation and mineral alteration. Activity in the subcontinental deep biosphere can be traced through the geological record back to the Precambrian. Before the colonization of the Earth's surface by land plants, a geologically recent event, subsurface life probably dominated the planet's biomass. In regions of thick ice sheets the base of the ice sheet, where liquid water is stable and a sediment layer is created by glacial erosion, can be regarded as a deep biosphere habitat. This environment may be rich in dissolved organic carbon and nutrients accumulated from dissolving ice, and from weathering of the bedrock and the sediment layer. PMID- 26667909 TI - Advances in modelling subglacial lakes and their interaction with the Antarctic ice sheet. AB - Subglacial lakes have long been considered hydraulically isolated water bodies underneath ice sheets. This view changed radically with the advent of repeat-pass satellite altimetry and the discovery of multiple lake discharges and water infill, associated with water transfer over distances of more than 200 km. The presence of subglacial lakes also influences ice dynamics, leading to glacier acceleration. Furthermore, subglacial melting under the Antarctic ice sheet is more widespread than previously thought, and subglacial melt rates may explain the availability for water storage in subglacial lakes and water transport. Modelling of subglacial water discharge in subglacial lakes essentially follows hydraulics of subglacial channels on a hard bed, where ice sheet surface slope is a major control on triggering subglacial lake discharge. Recent evidence also points to the development of channels in deformable sediment in West Antarctica, with significant water exchanges between till and ice. Most active lakes drain over short time scales and respond rapidly to upstream variations. Several Antarctic subglacial lakes exhibit complex interactions with the ice sheet due to water circulation. Subglacial lakes can therefore-from a modelling point of view be seen as confined small oceans underneath an imbedded ice shelf. PMID- 26667910 TI - The distribution of basal water between Antarctic subglacial lakes from radar sounding. AB - Antarctica's subglacial lakes have two end member geophysical expressions: as hydraulically flat, radar reflective regions highlighted in ice surface topography and radar sounding profiles ('definite lakes'), and as localized sites of elevation change identified from repeat elevation observations ('active lakes') that are often found in fast flowing ice streams or enhanced ice flow tributaries. While 'definite lakes' can be identified readily by high bed reflectivity in radar sounding, the identification and characterization of less distinct subglacial lakes and water systems with radar sounding are complicated by variable radio-wave attenuation in the overlying ice. When relying on repeat elevation observations, the relatively short times series and biased distribution of elevation observations, along with the episodic nature of 'active lake' outflow and replenishment, limit our understanding of how water flows under the ice sheet. Using recently developed methods for quantifying the radar scattering behaviour of the basal interface of the ice, we can avoid the problem of attenuation, and observe the plumbing of the subglacial landscape. In West Antarctica's Ross Sea Embayment, we confirm that extensive distributed water systems underlie these ice streams. Distributed water sheets are upstream in the onset regions of fast flow, while canal systems underly downstream regions of fast flow. In East Antarctica, we use specularity analysis to recover substantial hydraulic connectivity extending beyond previous knowledge, connecting the lakes already delineated by traditional radar sounding or surface elevation transients. PMID- 26667908 TI - Subglacial Lake Whillans microbial biogeochemistry: a synthesis of current knowledge. AB - Liquid water occurs below glaciers and ice sheets globally, enabling the existence of an array of aquatic microbial ecosystems. In Antarctica, large subglacial lakes are present beneath hundreds to thousands of metres of ice, and scientific interest in exploring these environments has escalated over the past decade. After years of planning, the first team of scientists and engineers cleanly accessed and retrieved pristine samples from a West Antarctic subglacial lake ecosystem in January 2013. This paper reviews the findings to date on Subglacial Lake Whillans and presents new supporting data on the carbon and energy metabolism of resident microbes. The analysis of water and sediments from the lake revealed a diverse microbial community composed of bacteria and archaea that are close relatives of species known to use reduced N, S or Fe and CH4 as energy sources. The water chemistry of Subglacial Lake Whillans was dominated by weathering products from silicate minerals with a minor influence from seawater. Contributions to water chemistry from microbial sulfide oxidation and carbonation reactions were supported by genomic data. Collectively, these results provide unequivocal evidence that subglacial environments in this region of West Antarctica host active microbial ecosystems that participate in subglacial biogeochemical cycling. PMID- 26667903 TI - Molecular specification of germ layers in vertebrate embryos. AB - In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this process of cellular diversification is the formation of the three germ layers: ectoderm, endoderm and mesoderm. The ectoderm gives rise to the nervous system, epidermis and various neural crest-derived tissues, the endoderm goes on to form the gastrointestinal, respiratory and urinary systems as well as many endocrine glands, and the mesoderm will form the notochord, axial skeleton, cartilage, connective tissue, trunk muscles, kidneys and blood. Classic experiments in amphibian embryos revealed the tissue interactions involved in germ layer formation and provided the groundwork for the identification of secreted and intracellular factors involved in this process. We will begin this review by summarising the key findings of those studies. We will then evaluate them in the light of more recent genetic studies that helped clarify which of the previously identified factors are required for germ layer formation in vivo, and to what extent the mechanisms identified in amphibians are conserved across other vertebrate species. Collectively, these studies have started to reveal the gene regulatory network (GRN) underlying vertebrate germ layer specification and we will conclude our review by providing examples how our understanding of this GRN can be employed to differentiate stem cells in a targeted fashion for therapeutic purposes. PMID- 26667911 TI - Antarctic Cenozoic climate history from sedimentary records: ANDRILL and beyond. AB - Mounting evidence from models and geological data implies that the Antarctic Ice Sheet may behave in an unstable manner and retreat rapidly in response to a warming climate, which is a key factor motivating efforts to improve estimates of Antarctic ice volume contributions to future sea-level rise. Here, we review Antarctic cooling history since peak temperatures of the Middle Eocene Climatic Optimum (approx. 50 Ma) to provide a framework for future initiatives to recover sediment cores from subglacial lakes and sedimentary basins in Antarctica's continental interior. While the existing inventory of cores has yielded important insights into the biotic and climatic evolution of Antarctica, strata have numerous and often lengthy time breaks, providing a framework of 'snapshots' through time. Further cores, and more work on existing cores, are needed to reconcile Antarctic records with the more continuous 'far-field' records documenting the evolution of global ice volume and deep-sea temperature. To achieve this, we argue for an integrated portfolio of drilling and coring missions that encompasses existing methodologies using ship- and sea-ice-/ice shelf-based drilling platforms as well as recently developed seafloor-based drilling and subglacial access systems. We conclude by reviewing key technological issues that will need to be overcome. PMID- 26667912 TI - Characterization of subglacial Lake Vostok as seen from physical and isotope properties of accreted ice. AB - Deep drilling at the Vostok Station has reached the surface of subglacial Lake Vostok (LV) twice-in February 2012 and January 2015. As a result, three replicate cores from boreholes 5G-1, 5G-2 and 5G-3 became available for detailed and revalidation analyses of the 230 m thickness of the accreted ice, down to its contact with water at 3769 m below the surface. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of LV, has been discerned in the three different properties of the accreted ice: the ice texture, the isotopic and the gas content of the ice. These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. The latter implies that the surface water may be not representative enough to study LV's behaviour, and that direct sampling of the lake at different depths is needed in order to move ahead with our understanding of the lake's hydrological regime. PMID- 26667913 TI - Clean subglacial access: prospects for future deep hot-water drilling. AB - Accessing and sampling subglacial environments deep beneath the Antarctic Ice Sheet presents several challenges to existing drilling technologies. With over half of the ice sheet believed to be resting on a wet bed, drilling down to this environment must conform to international agreements on environmental stewardship and protection, making clean hot-water drilling the most viable option. Such a drill, and its water recovery system, must be capable of accessing significantly greater ice depths than previous hot-water drills, and remain fully operational after connecting with the basal hydrological system. The Subglacial Lake Ellsworth (SLE) project developed a comprehensive plan for deep (greater than 3000 m) subglacial lake research, involving the design and development of a clean deep-ice hot-water drill. However, during fieldwork in December 2012 drilling was halted after a succession of equipment issues culminated in a failure to link with a subsurface cavity and abandonment of the access holes. The lessons learned from this experience are presented here. Combining knowledge gained from these lessons with experience from other hot-water drilling programmes, and recent field testing, we describe the most viable technical options and operational procedures for future clean entry into SLE and other deep subglacial access targets. PMID- 26667914 TI - Recent advances in understanding Antarctic subglacial lakes and hydrology. AB - It is now well documented that over 400 subglacial lakes exist across the bed of the Antarctic Ice Sheet. They comprise a variety of sizes and volumes (from the approx. 250 km long Lake Vostok to bodies of water less than 1 km in length), relate to a number of discrete topographic settings (from those contained within valleys to lakes that reside in broad flat terrain) and exhibit a range of dynamic behaviours (from 'active' lakes that periodically outburst some or all of their water to those isolated hydrologically for millions of years). Here we critique recent advances in our understanding of subglacial lakes, in particular since the last inventory in 2012. We show that within 3 years our knowledge of the hydrological processes at the ice-sheet base has advanced considerably. We describe evidence for further 'active' subglacial lakes, based on satellite observation of ice-surface changes, and discuss why detection of many 'active' lakes is not resolved in traditional radio-echo sounding methods. We go on to review evidence for large-scale subglacial water flow in Antarctica, including the discovery of ancient channels developed by former hydrological processes. We end by predicting areas where future discoveries may be possible, including the detection, measurement and significance of groundwater (i.e. water held beneath the ice-bed interface). PMID- 26667915 TI - Enabling clean access into Subglacial Lake Whillans: development and use of the WISSARD hot water drill system. AB - Clean hot water drill systems (CHWDSs) are used with clean access protocols for the exploration of subglacial lakes and other subglacial aquatic environments (e.g. ice-shelf cavities) in Antarctica. A CHWDS developed for the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project by the Science Management Office at the University of Nebraska-Lincoln (UNL-SMO), USA, was specifically designed for use in West Antarctica, where the US Antarctic Program's South Pole Traverse could assist with logistical support. The initial goal was to provide clean access holes through ice up to 1000 m thick following environmental stewardship guidelines; however, the existing design allows this CHWDS to be used for ice thicknesses up to 2000 m following modifications to accommodate longer hose lengths. In January 2013, the WISSARD CHWDS successfully provided for the first time a clean access borehole through 800 m of ice into Subglacial Lake Whillans beneath the West Antarctic Ice Sheet for the deployment of scientific instruments and sampling tools. The development and initial use of the WISSARD CHWDS required the project team to address a number of constraints while providing contingencies to meet the defined project scope, schedule and budget. PMID- 26667916 TI - Geology and environments of subglacial Lake Vostok. AB - The reconstruction of the geological (tectonic) structure and environments of subglacial Lake Vostok is based on geophysical surveys and the study of mineral particles found in cores of accreted ice and frozen lake water (sampled after the lake was unsealed). Seismic reflection and refraction investigations conducted in the southern part of Lake Vostok show very thin (200-300 m) sedimentary cover overlying a crystalline basement. Most of this thin veneer is thought to have been deposited during temperate-glacial conditions in Oligocene to Middle Miocene time (ca 34-14 Ma). The composition of the lake-bottom sediments can be deduced from mineral inclusions found in cores of accreted ice. Inclusions are represented by soft aggregates consisting mainly of clay-mica minerals and micrometre-sized quartz grains. Some of these inclusions contain subangular to semi-rounded rock clasts (siltstones and sandstones) ranging from 0.3 to 8 mm in size. In total, 31 zircon grains have been identified in two rock clasts and dated using SHRIMP-II. The ages of the studied zircons range from 0.6 to 2.0 Ga with two distinct clusters between 0.8 and 1.15 Ga and between 1.6 and 1.8 Ga. Rock clasts obviously came from the western lake shore, which is thus composed of terrigenous strata with an age of not older than 600 Ma. The sedimentary nature of the western lake shore is also confirmed by seismic refraction data showing seismic velocities there of 5.4-5.5 km s(-1) at the bedrock surface. After Lake Vostok was unsealed, its water (frozen and sampled next season) was also studied with scanning electron microscopy and X-ray microprobe analysis. This study showed the existence of calcium carbonate and silica microparticles (10-20 MUm across) in frozen water. PMID- 26667917 TI - Antarctic subglacial lake exploration: first results and future plans. AB - After more than a decade of planning, three attempts were made in 2012-2013 to access, measure in situ properties and directly sample subglacial Antarctic lake environments. First, Russian scientists drilled into the top of Lake Vostok, allowing lake water to infiltrate, and freeze within, the lower part of the ice core borehole, from which further coring would recover a frozen sample of surface lake water. Second, UK engineers tried unsuccessfully to deploy a clean-access hot-water drill, to sample the water column and sediments of subglacial Lake Ellsworth. Third, a US mission successfully drilled cleanly into subglacial Lake Whillans, a shallow hydraulically active lake at the coastal margin of West Antarctica, obtaining samples that would later be used to prove the existence of microbial life and active biogeochemical cycling beneath the ice sheet. This article summarizes the results of these programmes in terms of the scientific results obtained, the operational knowledge gained and the engineering challenges revealed, to collate what is known about Antarctic subglacial environments and how to explore them in future. While results from Lake Whillans testify to subglacial lakes as being viable biological habitats, the engineering challenges to explore deeper more isolated lakes where unique microorganisms and climate records may be found, as exemplified in the Lake Ellsworth and Vostok missions, are considerable. Through international cooperation, and by using equipment and knowledge of the existing subglacial lake exploration programmes, it is possible that such environments could be explored thoroughly, and at numerous sites, in the near future. PMID- 26667918 TI - Technologies for retrieving sediment cores in Antarctic subglacial settings. AB - Accumulations of sediment beneath the Antarctic Ice Sheet contain a range of physical and chemical proxies with the potential to document changes in ice sheet history and to identify and characterize life in subglacial settings. Retrieving subglacial sediments and sediment cores presents several unique challenges to existing technologies. This paper briefly reviews the history of sediment sampling in subglacial environments. It then outlines some of the technological challenges and constraints in developing the corers being used in sub-ice shelf settings (e.g. George VI Ice Shelf and Larsen Ice Shelf), under ice streams (e.g. Rutford Ice Stream), at or close to the grounding line (e.g. Whillans Ice Stream) and in subglacial lakes deep under the ice sheet (e.g. Lake Ellsworth). The key features of the corers designed to operate in each of these subglacial settings are described and illustrated together with comments on their deployment procedures. PMID- 26667919 TI - Preface. PMID- 26667920 TI - Probe technologies for clean sampling and measurement of subglacial lakes. AB - It is 4 years since the subglacial lake community published its plans for accessing, sampling, measuring and studying the pristine, and hitherto enigmatic and very different, Antarctic subglacial lakes, Vostok, Whillans and Ellsworth. This paper summarizes the contrasting probe technologies designed for each of these subglacial environments and briefly updates how these designs changed or were used differently when compared to previously published plans. A detailed update on the final engineering design and technical aspects of the probe for Subglacial Lake Ellsworth is presented. This probe is designed for clean access, is negatively buoyant (350 kg), 5.2 m long, 200 mm in diameter, approximately cylindrical and consists of five major units: (i) an upper power and communications unit attached to an optical and electrical conducting tether, (ii) (iv) three water and particle samplers, and (v) a sensors, imaging and instrumentation pack tipped with a miniature sediment corer. To date, only in Subglacial Lake Whillans have instruments been successfully deployed. Probe technologies for Subglacial Lake Vostok (2014/15) and Lake Ellsworth (2012/13) were not deployed for technical reasons, in the case of Lake Ellsworth because hot-water drilling was unable to access the lake during the field season window. Lessons learned and opportunities for probe technologies in future subglacial access missions are discussed. PMID- 26667921 TI - Effects of Simultaneous or Sequential Weight Loss Diet and Aerobic Interval Training on Metabolic Syndrome. AB - Our purpose in this study was to investigate efficient and sustainable combinations of exercise and diet-induced weight loss (DIET), in order to combat obesity in metabolic syndrome (MetS) patients. We examined the impact of aerobic interval training (AIT), followed by or concurrent to a DIET on MetS components. 36 MetS patients (54+/-9 years old; 33+/-4 BMI; 27 males and 9 females) underwent 16 weeks of AIT followed by another 16 weeks without exercise from the fall of 2013 to the spring of 2014. Participants were randomized to AIT without DIET (E CON, n=12), AIT followed by DIET (E-then-D, n=12) or AIT concurrent with DIET (E+D, n=12) groups. Body weight decreased below E CON similarly in the E-then-D and E+D groups (~5%). Training improved blood pressure and cardiorespiratory fitness (VO2peak) in all groups with no additional effect of concurrent weight loss. However, E+D improved insulin sensitivity (HOMA) and lowered plasma triglycerides and blood cholesterol below E CON and E-then-D (all P<0.05). Weight loss in E-then-D in the 16 weeks without exercise lowered HOMA to the E+D levels and maintained blood pressure at trained levels. Our data suggest that a new lifestyle combination consisting of aerobic interval training followed by weight loss diet is similar, or even more effective on improving metabolic syndrome factors than concurrent exercise plus diet. PMID- 26667922 TI - Post-activation Potentiation in Propulsive Force after Specific Swimming Strength Training. AB - We investigated whether a conditioning activity (8*12.5 m with 2.5 min-interval using both hand paddles and parachute) induced post-activation potentiation in swimming propulsive force and whether a swimmer's force level affected a post activation potentiation response. 8 competitive swimmers (5 males and 3 females, age: 18.4+/-1.3 years; IPS=796+/-56) performed a 10 s maximum tethered swimming test 8 and 4 min before (the highest value was considered as PRE), and 2.5 and 6.5 min after (POST1 and POST2, respectively) the conditioning activity. Rate of force development was not affected, but peak force in POST1 (p=0.02) and impulse in both POST1 (p=0.007) and POST2 (p=0.004) were reduced. Possibly the conditioning activity induced greater fatigue than post-activation potentiation benefits. For instance, the number of repetitions might have been excessive, and rest intervals between the conditioning activity and POST1 and POST2 were possibly too short. There were positive correlations between PRE peak force and changes in peak force and rate of force development. Although conditioning activity was detrimental, positive correlations suggest that weaker swimmers experience a deterioration of performance more than the stronger ones. This conditioning activity is not recommended for swimmers with the current competitive level before a competitive event. PMID- 26667923 TI - Short-term Recovery Following Resistance Exercise Leading or not to Failure. AB - This study analyzed the time course of recovery following 2 resistance exercise protocols differing in level of effort: maximum (to failure) vs. half-maximum number of repetitions per set. 9 males performed 3 sets of 4 vs. 8 repetitions with their 80% 1RM load, 3*4(8) vs. 3*8(8), in the bench press and squat. Several time-points from 24 h pre- to 48 h post-exercise were established to assess the mechanical (countermovement jump height, CMJ; velocity against the 1 m.s(-1) load, V1-load), biochemical (testosterone, cortisol, GH, prolactin, IGF-1, CK) and heart rate variability (HRV) and complexity (HRC) response to exercise. 3*8(8) resulted in greater neuromuscular fatigue (higher reductions in repetition velocity and velocity against V1-load) than 3*4(8). CMJ remained reduced up to 48 h post-exercise following 3*8(8), whereas it was recovered after 6 h for 3*4(8). Significantly greater prolactin and IGF-1 levels were found for 3*8(8) vs. 3*4(8). Significant reductions in HRV and HRC were observed for 3*8(8) vs. 3*4(8) in the immediate recovery. Performing a half-maximum number of repetitions per set resulted in: 1) a stimulus of faster mean repetition velocities; 2) lower impairment of neuromuscular performance and faster recovery; 3) reduced hormonal response and muscle damage; and 4) lower reduction in HRV and HRC following exercise. PMID- 26667924 TI - Immediate Effects of Different Trunk Exercise Programs on Jump Performance. AB - The aim of this study was to investigate the immediate effects of trunk stabilization exercise (SE) and conventional trunk exercise (CE) programs on jump performance. 13 adolescent male soccer players performed 2 kinds of jump testing before and immediate after 3 experimental conditions: SE, CE, and non-exercise (NE). The SE program consisted of the elbow-toe, hand-knee, and back bridge, and the CE program consisted of the sit-up, sit-up with trunk rotation and back extension. Testing of a countermovement jump (CMJ) and rebound jump (RJ) were performed to assess jump performance. Jump height of the CMJ and RJ-index, contact time, and jump height of the RJ were analyzed. The RJ index was improved significantly only after SE (p=0.017). However, contact time and jump height did not improve significantly in the SE condition. Moreover, no significant interaction or main effects of time or group were observed in the CMJ. Consequently, this study showed the different immediate effect on the RJ between the SE and CE, and suggested the possibility that the SE used in this study is useful as a warm-up program to improve the explosive movements. PMID- 26667925 TI - Jump Squat is More Related to Sprinting and Jumping Abilities than Olympic Push Press. AB - The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise. PMID- 26667926 TI - The Influence of Optimal Handheld Load on the Technical Ability to Apply Ground Reaction Forces during Horizontal Jumping in Female Netball Players. AB - Handheld load has been reported to enhance horizontal jump performance, however little is known about its influence on ground reaction forces (GRF), especially in female athletes. This study investigated the effects of individualized optimal handheld loading on the technical and physical ability to apply GRF during horizontal jumping in female netball players. Maximal effort, single standing, horizontal jumps were performed by 13 female netballers. Participants performed the jumps under 2 conditions: 1) unloaded, and 2) loaded. Eccentric mean horizontal GRF significantly increased with loading (p<0.05; Effect Size [ES]= 0.74). The ratio of horizontal-to-total GRF significantly increased (p<0.05; ES=0.57), however resultant GRF did not, suggesting that the technical ability to apply force in the direction of intended movement may be of greater importance than the magnitude of force applied. Jump distance also increased from 188.2+/ 16.1 cm to 196.4+/-13.6 cm (p<0.01; ES=0.55) with handheld load. In conclusion, individualized optimal handheld loading improved single horizontal jump performance in this population of athletes; most likely through various mechanisms that allowed for increased eccentric horizontal GRFs and the technical ability of force application. Findings could have practical implications for the strength and conditioning coach, trainer and athlete. PMID- 26667927 TI - AquaTrainer(r) Snorkel does not Increase Hydrodynamic Drag but Influences Turning Time. AB - Our purpose was to verify if the use of the new AquaTrainer((r)) respiratory snorkel lead to an increase of front crawl hydrodynamic drag and whether the constraint of using an adapted turning technique influences its corresponding turning time. 12 swimmers performed 2 (without and with snorkel) 12*25 front crawl repetitions from low to maximal velocity on the measuring active drag system. Complementarily, 3 swimming turns were compared: open turn with snorkel, tumble turn and open turn without snorkel. Drag values were similar without vs. with snorkel at 0.9, 1.1, 1.3, 1.5 and 1.7 m.s(-1) velocities: 15.84 +/-5.32 vs. 16.18+/-4.81, 25.60+/-6.69 vs. 26.03+/-6.17, 38.37+/-8.04 vs. 38.88+/-7.56, 54.64+/-10.06 vs. 55.08+/-9.55, 74.77+/-14.09 vs. 74.92+/-13.14 N, (respectively, p>=0.05), and high agreement between conditions was observed (p<0.01). Front crawl swimming with snorkel using the open turn implied an increase in turning time of 14.2 and 5.1% than the tumble turn and open turn without the apparatus (p<0.01). AquaTrainer((r)) snorkel does not lead to an increase in active drag during front crawl performed at a large range of velocities and, consequently, the metabolic energy necessary to overcome total drag will not be affected. However, turning with it requires an additional time that should be taken into account in scientific research and training conditions. PMID- 26667928 TI - Low-load Slow Movement Squat Training Increases Muscle Size and Strength but Not Power. AB - We tested a hypothesis that low-load squat training with slow movement and tonic force generation (LST) would increase muscle size and strength but not necessarily power. Healthy young men were assigned to LST [50% one-repetition maximum (1-RM) load, 3 s for lowering/lifting without pause: n=9] or low-load normal speed (LN: 50% 1-RM load, 1 s for lowering/lifting with 1-s pause; n=7) groups. Both groups underwent an 8-week squat training program (10 repetitions/set, 3 sets/day, and 3 days/week) using the assigned methods. Before and after the intervention, quadriceps femoris muscle thickness, maximal torque during isometric hip extension and knee extension, 1-RM squat, lifting power from squatting position and rate of electromyography rise (RER) in knee extensors during the task, leg extension power and vertical jump height were measured. After the intervention, the LN group showed no changes in all the variables. The LST group significantly (P<0.05) increased muscle thickness (6-10%), isometric hip extension torque (18%) and 1-RM squat (10%), but not isometric knee extension torque, lifting power and RER, leg extension power and vertical jump height. These results suggest that LST can increase muscle size and task-related strength, but has little effect on power production during dynamic explosive movements. PMID- 26667929 TI - Effects of Stable and Unstable Resistance Training in an Altered-G Environment on Muscle Power. AB - The study evaluated the effect of 4 weeks of combined resistance-balance training and resistance training alone in a 90 degrees tilted environment on muscle power. Two groups of healthy young subjects performed leg extensions while in a supine position, either on a firm surface along a linear track or on an unstable surface requiring mediolateral balancing movements. Power and force during squats were measured at isokinetic velocities of 10 and 35 deg/s. Results showed significantly greater gains in peak force (44.1%; F(1,21)=8.876, p=0.026), mean force (58.6%; F(1,21)=16.136, p=0.013), peak power (58.7%; F(1,21)=18.754, p=0.009), and mean power (59.2%; F(1,21)=23.114, p=0.007) at the velocity of 35 deg/s after stable than unstable resistance training. However, there were no significant between-groups differences in pre-post training gains in peak force (10.4%; F(1,21)=1.965, p=0.74), mean force (10.3%; F(1,21)=1.889, p=0.80), peak power (12.9%; F(1,21)=2.980, p=0.49), and mean power (19.1%; F(1,21)=3.454, p=0.36) during squats at the velocity of 10 deg/s. Resistance exercises under stable conditions performed in a 90 degrees tilted environment are more effective in the improvement of high velocity muscle power than their use in combination with balance exercises. Such training may be applicable in pre- and in-flight exercise regimens for astronauts and in functional rehabilitation of bed-ridden patients. PMID- 26667930 TI - The 14/15 association as a paradigmatic example of tracing karyotype evolution in New World monkeys. AB - Fluorescence in situ hybridization (FISH), especially chromosome painting, has been extensively exploited in the phylogenetic reconstruction of primate evolution. Although chromosome painting is a key method to map translocations, it is not effective in detecting chromosome inversions, which may be up to four times more frequent than other chromosomal rearrangements. BAC-FISH instead can economically delineate marker order and reveal intrachromosomal rearrangements. However, up to now, BAC-FISH was rarely used to study the chromosomes of New World monkeys partly due to technical difficulties. In this paper, we used BAC FISH to disentangle the complex evolutionary history of the ancestral 14/15 association in NWMs, beginning from the squirrel monkey (Saimiri boliviensis). To improve the hybridization efficiency of BAC-FISH in NWMs, we "translated" the human BACs into Callithrix jacchus (CJA) BACs, which yielded much higher hybridization efficiencies on other NWM species than human BACs. Our results disclosed 14 synteny blocks in squirrel monkeys, 7 more than with chromosome painting. We then applied a subset of CJA BACs on six other NWM species. The comparison of the hybridization pattern of these species contained phylogenetic information to discriminate evolutionary relationships. Notably Aotus was found to share an inversion with Callithrix, thus definitely assigning the genus Aotus to Cebidae. The present study can be seen as a paradigmatic approach to investigate the phylogenetics of NWMs by molecular cytogenetics. PMID- 26667931 TI - Mapping centromeres of microchromosomes in the zebra finch (Taeniopygia guttata) using half-tetrad analysis. AB - Centromeres usually consist of hundreds of kilobases of repetitive sequence which renders them difficult to assemble. As a consequence, centromeres are often missing from assembled genomes and their locations on physical chromosome maps have to be inferred from flanking sequences via fluorescence in situ hybridization (FISH). Alternatively, centromere positions can be mapped using linkage analyses in accidentally triploid individuals formed by half-tetrads (resulting from the inheritance of two chromatids from a single meiosis). The current genome assembly of the zebra finch (Taeniopygia guttata) comprises 32 chromosomes, but only for the ten largest chromosomes centromere positions have been mapped using FISH. We here map the positions of most of the remaining centromeres using half-tetrad analyses. For this purpose, we genotyped 37 zebra finches that were triploid or tetraploid due to inheritance errors (and mostly died as embryos) together with their parents at 64 microsatellite markers (at least two per chromosome). Using the information on centromere positions on the ten largest chromosomes, we were able to identify 12 cases of non-disjunction in maternal meiosis I and 10 cases of non-disjunction in maternal meiosis II. These 22 informative cases allowed us to infer centromere positions on additional 19 microchromosomes in reference to the current genome assembly. This knowledge will be valuable for studies of chromosome evolution, meiotic drive and species divergence in the avian lineage. PMID- 26667933 TI - Palliative embolization for metastases of the spine. AB - BACKGROUND: To present palliative selective and superselective arterial embolization with N-butyl-cyanoacrylate for cancer patients with spinal metastases. MATERIALS AND METHODS: We studied the files of 164 cancer patients (94 men and 70 women; mean age 57.6 years; range 35-81 years) treated from March 2003 to March 2013 with 178 selective arterial embolization procedures for metastases of the spine from variable primary cancers. We evaluated the technical success of the embolization procedure with post-procedural angiography, the clinical effect in pain relief, need for analgesics and tumor size reduction, and the embolization-related complications. RESULTS: Post-embolization angiography showed complete occlusion of the pathological feeding vessels in all procedures. Pain score and need for analgesics reduced by 50 % in 159 patients (97 %); no response was achieved in five patients with metastases of the sacrum. The mean duration of pain relief was 9.2 months (range 1-12 months). Metastatic tumor size reduced from a mean of 5.5 cm (range 3.5-7.5 cm) pre-embolization to a mean of 4.5 cm (range 3-5 cm) at the 6-month follow-up; the difference was not statistically significant. Ninety-three patients (56.7 %) experienced embolization-related complications the most common being post-embolization syndrome (80 patients, 48.8 %) followed by leg paresthesias (ten patients, 6 %), and rupture of a lumbar artery (one patient, 0.6 %). CONCLUSION: Selective arterial embolization with N-butyl-cyanoacrylate should be considered for pain palliation of patients with metastases of the spine. However, pain relief is temporary, and complications, although minor may occur. PMID- 26667932 TI - Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases. AB - TGFbeta is a known driver of epithelial-mesenchymal transition (EMT) which is associated with tumor aggressiveness and metastasis. However, EMT has not been fully explored in clinical specimens of castration-resistant prostate cancer (CRPC) metastases. To assess EMT in CRPC, gene expression analysis was performed on 149 visceral and bone metastases from 62 CRPC patients and immunohistochemical analysis was performed on 185 CRPC bone and visceral metastases from 42 CRPC patients. In addition, to assess the potential of metastases to seed further metastases the mitochondrial genome was sequenced at different metastatic sites in one patient. TGFbeta was increased in bone versus visceral metastases. While primarily cytoplasmic; nuclear and cytoplasmic Twist were significantly higher in bone than in visceral metastases. Slug and Zeb1 were unchanged, with the exception of nuclear Zeb1 being significantly higher in visceral metastases. Importantly, nuclear Twist, Slug, and Zeb1 were only present in a subset of epithelial cells that had an EMT-like phenotype. Underscoring the relevance of EMT-like cells, mitochondrial sequencing revealed that metastases could seed additional metastases in the same patient. In conclusion, while TGFbeta expression and EMT-associated protein expression is present in a considerable number of CRPC visceral and bone metastases, nuclear Twist, Slug, and Zeb1 localization and an EMT-like phenotype (elongated nuclei and cytoplasmic compartment) was only present in a small subset of CRPC bone metastases. Mitochondrial sequencing from different metastases in a CRPC patient provided evidence for the seeding of metastases from previously established metastases, highlighting the biological relevance of EMT-like behavior in CRPC metastases. PMID- 26667934 TI - Body Esteem Among Women with Multiple Sclerosis and its Relationship with Demographic, Clinical and Socio-Psychological Factors. AB - PURPOSE: The principal aim of this study was to verify if specific socio demographic, clinical, and socio-psychological factors are correlates of body esteem in women with multiple sclerosis (MS). METHODS: The study included 185 women with MS who completed the Body Esteem Scale (BES), Rosenberg Self-Esteem Scale (RSES), Multiple Sclerosis Impact Scale (MSIS-29), Brief Illness Perception Questionnaire (B-IPQ), Actually Received Support Scale (a part of the Berlin Social Support Scale), and Expanded Disability Status Scale (EDSS). The patients were recruited as a result of cooperation with the Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. The demographic characteristics of the participants and their illness-related problems were determined with a self-report survey. RESULTS: A hierarchical multiple regression revealed that four factors, psychological condition (R (2) = 0.23, p <= 0.001), received support (R (2) = 0.28, p <= 0.001), personal control (R (2) = 0.30, p <= 0.001), and physical condition (R (2) = 0.31, p <= 0.001), were significant correlates of the general body esteem in our study group of women with MS. The model explained 31 % of variance in body esteem. CONCLUSION: Positive body esteem, an important component of self-esteem in women with MS, is associated with better social support, overcoming negative illness-related appraisals and improvement of psychological well-being. Subjective perception of a negative impact of MS on one's physical condition may be helpful in the identification of women with MS being at increased risk of decreased body esteem. PMID- 26667935 TI - Serum Trace Element Profiles, Prolactin, and Cortisol in Transient Ischemic Attack Patients. AB - The primary aim of the present study was to assess the association between trace element status, brain damage biomarkers, cortisol, and prolactin levels in transient ischemic attack (TIA) patients. Ten male and 10 female TIA patients were involved in this study. Age, gender, and BMI-matched volunteers served as the respective control group. Serum samples were examined for complement components C4 and C3a, vascular endothelial growth factor (VEGF), S100B, NR2 antibodies (NR2Ab), total antioxidant status (TAS), cortisol, and prolactin. Trace element concentration in serum samples was assessed using inductively coupled plasma mass spectrometry at NexION 300D. The obtained data indicate that both male and female TIA patients were characterized by the increased C4 and prolactin concentrations. At the same time, serum VEGF levels were elevated in only men, whereas TAS values were decreased in women with TIA. Serum cortisol concentrations were significantly increased only in female TIA patients. Men and women with TIA were characterized by a 32 and 44 % decrease in serum Fe content. A two- and threefold increase in serum V content was observed in TIA females and males, respectively. Women with TIA had 60 % higher values of serum B, whereas male patients were characterized by a sevonfold increase in boron content in comparison to the control values. TIA also resulted in decreased serum Cu content in women and elevation of I, Li, Mn, Se, Zn, As, Pb, Ni, and Sr levels in men. Correlation analysis revealed a significant association between trace elements concentration and the studied parameters. PMID- 26667936 TI - A Strategy to Employ Clitoria ternatea as a Prospective Brain Drug Confronting Monoamine Oxidase (MAO) Against Neurodegenerative Diseases and Depression. AB - Ayurveda is a renowned traditional medicine practiced in India from ancient times and Clitoria ternatea is one such prospective medicinal herb incorporated as an essential constituent in a brain tonic called as medhya rasayan for treating neurological disorders. This work emphasises the significance of the plant as a brain drug there by upholding Indian medicine. The phytochemicals from the root extract were extricated using gas chromatography-mass spectrometry assay and molecular docking against the protein Monoamine oxidase was performed with four potential compounds along with four reference compounds of the plant. This persuades the prospect of C. ternatea as a remedy for neurodegenerative diseases and depression. The in silico assay enumerates that a major compound (Z)-9,17 octadecadienal obtained from the chromatogram with a elevated retention time of 32.99 furnished a minimum binding affinity energy value of -6.5 kcal/mol against monoamine oxidase (MAO-A). The interactions with the amino acid residues ALA 68, TYR 60 and TYR 69 were analogous to the reference compound kaempferol-3 monoglucoside with a least score of -13.90/-12.95 kcal/mol against the isoforms (MAO) A and B. This study fortifies the phytocompounds of C. ternatea as MAO inhibitors and to acquire a pharmaceutical approach in rejuvenating Ayurvedic medicine. PMID- 26667937 TI - Diterpenoids from the Roots of Salvia yunnanensis. AB - Two new diterpenoids, salyunnanins I and J (1 and 2), together with ten analogues, were isolated from the roots of Salvia yunnanensis. The structures of the new isolates, possessing different neo-clerodane and seco-abietane diterpenoid skeletons respectively, were elucidated on the basis of comprehensive spectroscopic data. All of the compounds were tested for the inhibitory activities against six human tumor lines in vitro, and several ones showed moderate cytotoxic activities. PMID- 26667938 TI - Correction to: Incorporating unnatural amino acids to engineer biocatalysts for industrial bioprocess applications. PMID- 26667941 TI - The development of two dimensional group IV chalcogenides, blocks for van der Waals heterostructures. AB - In this work, we introduce a series of two dimensional (2D) group IV chalcogenides (AX)2 with the building block X-A-A-X (A = Si, Ge, Sn, and Pb, and X = Se and Te) on the basis of ab initio calculations. The analysis of energy evaluation, lattice vibration as well as the chemical bonding demonstrate the good stability of these 2D materials. Furthermore, the pictures for the chemical bonding and electronic features of the 2D (AX)2 are drawn. Their narrow gapped semiconducting nature is unraveled. Especially, strong interactions between the electrons and phonons as well as the topological insulating nature in (SiTe)2 are observed. The present results indicate that such remarkable artificial 2D (AX)2 are building blocks for van der Waals heterostructure engineering, which shows potential applications in nanoscaled electronics and optoelectronics. PMID- 26667940 TI - Do frailty and cognitive impairment affect dual-task cost during walking in the oldest old institutionalized patients? AB - The objective of this study was to investigate dual-task costs in several elderly populations, including robust oldest old, frail oldest old with MCI, frail oldest old without MCI, and frail elderly with dementia. Sixty-four elderly men and women categorized into frail without MCI (age 93.4 +/- 3.2 years, n = 20), frail with MCI (age 92.4 +/- 4.2 years, n = 13), robust (age 88.2 +/- 4.1 years, n = 10), and patients with dementia (age 88.1 +/- 5.1 years, n = 21). Five-meter gait ability and timed-up-and-go (TUG) tests with single and dual-task performance were assessed in the groups. Dual-task cost in both 5-m habitual gait velocity test and TUG test was calculated by the time differences between single and dual task performance. The robust group exhibited better 5-m gait and TUG test performances in the single and dual-task conditions compared with the other three groups (P < 0.001), and the frail and frail + MCI groups exhibited better performances than the dementia group (P < 0.001). No significant differences were observed between the frail and frail + MCI groups. However, all groups exhibited lower gait velocities in the verbal and arithmetic task conditions, but the dual task cost of the groups were similar. Robust individuals exhibited superior single and dual-task walking performances than the other three groups, and the frail and frail + MCI individuals exhibited performances that were superior to those of the patients with dementia. However, the dual-task costs, i.e., the changes in gait performance when elderly participants switch from a single to a dual task, were similar among all four of the investigated groups. Therefore, these results demonstrated that the magnitude of the impairment in gait pattern is independent of frailty and cognitive impairment status. PMID- 26667942 TI - [The IMPROVE-IT trial]. PMID- 26667943 TI - [ESC guidelines for the diagnosis and management of pericardial disease: what should change in our clinical approach?]. PMID- 26667939 TI - Clinical Decision Support Tools for Selecting Interventions for Patients with Disabling Musculoskeletal Disorders: A Scoping Review. AB - Purpose We aimed to identify and inventory clinical decision support (CDS) tools for helping front-line staff select interventions for patients with musculoskeletal (MSK) disorders. Methods We used Arksey and O'Malley's scoping review framework which progresses through five stages: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies for analysis; (4) charting the data; and (5) collating, summarizing and reporting results. We considered computer-based, and other available tools, such as algorithms, care pathways, rules and models. Since this research crosses multiple disciplines, we searched health care, computing science and business databases. Results Our search resulted in 4605 manuscripts. Titles and abstracts were screened for relevance. The reliability of the screening process was high with an average percentage of agreement of 92.3 %. Of the located articles, 123 were considered relevant. Within this literature, there were 43 CDS tools located. These were classified into 3 main areas: computer-based tools/questionnaires (n = 8, 19 %), treatment algorithms/models (n = 14, 33 %), and clinical prediction rules/classification systems (n = 21, 49 %). Each of these areas and the associated evidence are described. The state of evidentiary support for CDS tools is still preliminary and lacks external validation, head-to-head comparisons, or evidence of generalizability across different populations and settings. Conclusions CDS tools, especially those employing rapidly advancing computer technologies, are under development and of potential interest to health care providers, case management organizations and funders of care. Based on the results of this scoping review, we conclude that these tools, models and systems should be subjected to further validation before they can be recommended for large-scale implementation for managing patients with MSK disorders. PMID- 26667944 TI - [Diuretics in heart failure and Karl Popper's turkey]. AB - Heart failure and renal failure often coexist in the same patient. This condition is commonly referred to as cardiorenal syndrome. When this occurs, patient survival worsens significantly with increasing degree of renal dysfunction. Management of this complex patient poses treatment challenges because of unstable hemodynamics (the problem is to reduce congestion without affecting organ perfusion) and very high mid-term in-hospital mortality. Congestion is a typical feature of this syndrome, and use of diuretics is mandatory. Loop diuretics should be administered first. However, poor attention to pharmacodynamic and pharmacokinetic properties of loop diuretics may contribute to the development of diuretic resistance leading to iatrogenic hyponatremia. Accordingly, emphasis is given to the importance of sequential nephron blockade to reduce the number of non-responder patients to diuretics and to recognize a possible role for acquaretics. PMID- 26667945 TI - [Ankle-brachial index: which clinical use?]. AB - The ankle-brachial index (ABI) obtained by the ankle/brachial blood pressure ratio is the gold standard for the diagnosis of peripheral arterial disease (PAD): <=0.9 is the cut-off value for PAD diagnosis and <=0.4 for the diagnosis of acute or chronic critical limb ischemia. Recently, the ABI has been proposed as an independent marker of cardiovascular (CV) risk, but its role remains debated. According to some authors, ABI improves CV risk scoring when added to traditional scores, such as the Framingham risk score, in both primary and secondary prevention: an ABI of <=0.9 or >=1.4 can allow for the selection of a subset of patients at high CV risk even if asymptomatic. On the contrary, others reported that ABI does not always improve CV risk scoring and, most importantly, optimization of therapy does not result in reduced rates of CV events. Side effects due to aggressive therapy were found to be more clinically relevant than the advantages deriving from a better control of CV risk. This review was aimed at defining the role of ABI as the gold standard for PAD screening and diagnosis, and as an independent early marker of CV risk, namely of coronary risk, taking into account the pros and cons reported in the literature. PMID- 26667946 TI - [Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. AB - BACKGROUND: Medical therapy with angiotensin II receptor blockers/angiotensin converting enzyme inhibitors and/or beta-blockers was reported to reduce aortic root dilatation rates in pediatric patients with Marfan syndrome. No data are available in the literature on losartan effects after 3 years of therapy. The aim of our study was to establish whether losartan reduces aortic root dilatation rates in pediatric patients with Marfan syndrome in the mid and long term. METHODS: This is a retrospective analysis of 38 pediatric patients with Marfan syndrome followed at the Marfan Clinic of S. Orsola-Malpighi Hospital of the University of Bologna (Italy). Aortic diameters were measured at sinuses of Valsalva and proximal ascending aorta with transthoracic echocardiography. RESULTS: After a mean follow-up of 4.5 +/- 2.5 years (range 2-9 years), aortic root z score at sinuses of Valsalva and proximal ascending aorta remained stable. The average annual rate of change in aortic root z score was -0.1 +/- 0.4 and 0 +/- 0.3 at sinuses of Valsalva and proximal ascending aorta, respectively. The mean dose of losartan was 0.7 +/- 0.3 mg/kg/day. Three patients were non responders, probably because of late beginning or low dose of therapy. Eight patients underwent cardiac surgery (aortic root surgery in 5 and mitral valve repair in 3), all of them started losartan later in life. CONCLUSIONS: Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term. Late beginning or low doses of losartan can turn off the effects of therapy. PMID- 26667947 TI - [Use of carbon dioxide as contrast agent to perform balloon angioplasty of the superficial femoral artery in a patient with severe renal impairment]. AB - Endovascular treatment of symptomatic atherosclerotic peripheral artery disease has gained widespread acceptance and is now recommended as the primary revascularization strategy in many clinical and interventional settings. Nevertheless, endovascular strategy finds a relative contraindication in patients affected by severe chronic kidney disease, because of nephrotoxicity of iodinated contrast medium. Carbon dioxide (CO2) angiography permits to obtain vascular angiography without the use of a iodinated contrast medium, therefore it is ideal in chronic kidney disease patients because it is not nephrotoxic and does not have appreciable medical contraindications. In this report we describe a case of percutaneous transluminal angioplasty of an occluded left superficial femoral artery using CO2as contrast medium, because of severe chronic kidney disease (glomerular filtration rate 28 ml/min/1.73 m2). This complex procedure required double vascular access with retrograde popliteal access associated with femoral access, which was performed successfully despite a very low use of iodinated contrast medium. This case report is also the starting point for a review of literature data regarding CO2 use for peripheral intervention. PMID- 26667948 TI - [A very rare coronary artery anomaly in a patient with corrected transposition of the great arteries]. AB - An 84-year-old male affected by correct transposition of the great arteries was admitted for an acute coronary syndrome, complicated by pulmonary edema. Coronary angiography showed a unique coronary anomaly: a common trunk, situated in the right sinus of Valsalva, gave rise to the left anterior descending coronary artery (LAD), the right coronary artery and an atrial branch; the circumflex coronary artery originated separately but close to the common trunk. A tight stenosis in the proximal LAD was successfully treated by percutaneous coronary intervention. PMID- 26667949 TI - [2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)]. PMID- 26667950 TI - [The IMPROVE-IT trial showed no favorable effects on well-defined and clinically relevant endpoints]. PMID- 26667951 TI - [In memoriam of Antonio Montinaro]. PMID- 26667952 TI - [Letter]. PMID- 26667953 TI - Metalation of tetraphenylporphyrin with nickel on a TiO2(110)-1 * 2 surface. AB - The in situ metalation of tetraphenylporphyrin (2HTPP) with Ni on the reconstructed TiO2(110)-1 * 2 surface, resulting in the formation of adsorbed nickel(II)-tetraphenylporphyrin (NiTPP), has been investigated by synchrotron radiation photoemission spectroscopy (SRPES), scanning tunnelling microscopy (STM) and ab initio Density Functional Theory (DFT) calculations. The metalation can be realized at room temperature irrespective of the deposition order of Ni and 2HTPP, which however leads to different metalation degrees. Increasing the substrate temperature or Ni : 2HTPP ratio results in higher metalation degree, which ultimately reaches its limit at ~85% (Ni : 2HTPP = 3 : 1) and ~49% (Ni : 2HTPP = 1 : 1) for post- and pre-deposition of Ni, respectively. The reaction from 2HTPP to NiTPP is accompanied by changes of the molecular adsorption conformation and the adsorption site from a tilted two-lobed feature on added Ti2O3 rows to a four-lobed feature on top of troughs or cross-links of the TiO2(110)-1 * 2 surface. This interpretation of the STM data is supported by DFT based STM simulations. PMID- 26667954 TI - Relevance of GP density to variations in prescribing safety assessed using the CPRD. PMID- 26667955 TI - CrossTalk opposing view: Heat acclimatization does not improve exercise performance in a cool condition. PMID- 26667956 TI - Early Ventricular Dysfunction After Anthracycline Chemotherapy in Children. AB - The aim of this study was to determine the effect of induction dose of anthracycline chemotherapy on the biventricular function among children with acute hematological malignancies (AHM) using tissue Doppler imaging (TDI) and 2D speckle tracking echocardiography (2D-STE). Thirty pediatric patients with AHM and a mean age of 9.24 +/- 4.14 years performed conventional echocardiography, TDI and 2D-STE. After induction chemotherapy, the RV showed mainly a diastolic alteration in its function manifested in significant reduction in the tricuspid TDI-derived E' and E'/A' ratio compared with the baseline (20.40 +/- 3.81 vs. 17.47 +/- 3.87 cm/s, p = 0.001, 1.29 +/- 0.27 vs. 1.03 +/- 0.37, p < 0.01, respectively), while the TDI-derived RV MPI and isovolumetric relaxation time of RV were significantly increased (0.32 +/- 0.06 vs. 0.36 +/- 0.08, p < 0.01, 24.73 +/- 8.62 vs. 28.47 +/- 11.51 ms, p < 0.05, respectively). The LV showed post chemotherapy mainly an alteration in its longitudinal systolic function in the form of a reduction in MAPSE (13.61 +/- 2.00 vs. 11.95 +/- 1.75 mm; p < 0.001), TDI-derived systolic velocity of lateral mitral annulus (10.98 +/- 2.34 vs. 10.03 +/- 1.83 cm/s, p < 0.05), 2D-STE-derived global longitudinal strain (-21.58 +/- 2.54 vs. -19.18 +/- 3.59 %, p = 0.001) and 2D-STE-derived global longitudinal strain rate (-1.76 +/- 0.22 vs. 1.55 +/- 0.29 1/s, p < 0.05), with preservation of LV diastolic function when compared to baseline. TDI and 2D-STE could be used for early detection of anthracycline-induced cardiotoxicity in the pediatric age group. Early after induction chemotherapy, the RV develops mainly diastolic dysfunction, while the LV showed a relative longitudinal systolic impairment. PMID- 26667957 TI - Three-Dimensional Rotational Angiography in the Pediatric Cath Lab: Optimizing Aortic Interventions. AB - The aim of this study was to evaluate usability and accuracy of three-dimensional rotational angiography (3DRA) during interventions of the aorta in congenital heart disease (CHD). 3DRA is an accurate, encompassing and fast imaging technique in the cath lab. However, there is only few published data about its use during interventions in CHD. Between January 2010 and January 2014, 3DRA was performed in 77 patients with aortic issues: in 65 % cases, an intervention was performed, of which 72 % had aortic isthmus stenosis. Data were obtained retrospectively. The accuracy of 3DRA was evaluated on the basis of comparative measurements (n = 60) of the aortic diameter between 3DRA and conventional biplane angiography. Measurements presented a high accuracy with an average deviation of 3.89 % [+/-3 %] and a significant correlation of r = 0.99 after Pearson (p < 0.0001). Clinical benefit was assessed using a five-point Likert scale and could be shown in 98 %. Comparison with a control group showed a reduced fluoroscopy time from 10.2 to 8.30 min (median, p < 0.01) and decreased radiation dose of 0.18 compared to 0.56 Gy cm(2)/kg (median, p < 0.02). The use of 3DRA in patients with aortic anomalies has advantages in comparison with conventional angiography. It improves diagnostic accuracy, and 3D guidance enables a faster and simplified intervention with enhanced patients' safety and the potential to reduce radiation dose. PMID- 26667958 TI - Right Ventricular Apical Flattening as an Echocardiographic Screening Tool for Right Ventricular Enlargement. AB - Right ventricular dilation is a common complication after tetralogy of Fallot (TOF) repair. Traditional echocardiographic assessments are imprecise due to the RV's location and complex geometry. We propose a novel echocardiographic measurement: RV apical flattening (RVAF) as a screening tool to help identify subjects with severe RV dilation. Patients with repaired TOF who had both echocardiograms and CMR's within 6-month interval at our institution were included in the study. The RVAF was measured in the four-chamber echocardiographic view as the minor length of RV cavity at the level of RV apical endocardium. Subjects were divided into two groups (group I: RVEDVi >= 150 ml/m(2) and group II; RVEDVi < 150 ml/m(2)). Echocardiogram and CMR data were compared between groups. A total of 75 subjects were included in the study. Mean age was 12.8 +/- 3.6 years. Group I had 36 subjects, and group II had 39 subjects. The mean RVAF was significantly higher in group I (2.7 +/- 0.5 cm) compared with group II (1.7 +/- 0.4 cm; p < 0.001). There was significant correlation between RVAF and RVEDVi (r = 0.81; p < 0.001). By ROC analysis, an RVAF cutoff value of 2.0 cm had 94 % sensitivity and 77 % specificity in identifying severe RV dilation (area under the curve 0.95). RVAF is a simple and effective echocardiographic screening tool to help identify severe RV dilation. In conjunction with other 2D echocardiographic parameters, this technique would help further refine echocardiography-guided patient selection for timing of CMR and pulmonary valve replacement. PMID- 26667959 TI - Intrapericardial NUT Midline Carcinoma: Unusual Presentation of a Rare Tumor and Literature Review with Management Considerations. AB - Rearrangements in the nuclear protein in testis (NUT) gene cause carcinomas that represent a rare but aggressive tumor type that often present at advanced stages in midline structures. Survival rarely exceeds 12 months from the time of diagnosis. There have been no reports of a primary cardiac presentation, and few studies have reported on the numerous treatment strategies. Given their aggressive and invasive nature, NUT midline carcinomas present a therapeutic dilemma. Treatment may include surgical resection, chemotherapy, or radiotherapy, but no consistently successful treatment has been established. Surgical resection is indicated to reduce symptomatic mass effect whenever present. Novel therapies with bromodomain extra-terminal inhibitors may be associated with potential survival benefit. Here, we describe an unusual presentation of this tumor. Literature review with management considerations is underlying. PMID- 26667960 TI - Changes in Ventricular Geometry Predict Severity of Right Ventricular Hypertension. AB - Changes in ventricular geometry are often seen in patients with right ventricular hypertension secondary to pulmonary hypertension (PH). Progressive systolic bowing of the inter-ventricular septum occurs with increasing right ventricular pressure (RVp) and can be quantified with the left ventricular end-systolic eccentricity index (LVEI). Only limited data exist in children to evaluate the relationship between the LVEI and invasive RVp. We sought to assess the correlation between the LVEI and an invasively measured peak systolic RVp to aortic pressure (pAo) ratio. Medical records of patients undergoing echocardiography within 30 days of right and left heart catheterization for evaluation of PH between February 2009 and March 2014 were retrospectively reviewed. Forty-six studies in 29 subjects (median age 3.8 years, 46 % female), with a median time from echocardiogram to catheterization of -1.0 days, were included for analysis. The mean LVEI was 1.6 +/- 0.5, and mean RVp/pAo ratio was 0.68 +/- 0.26. There was a significant positive correlation (r = 0.76, p < 0.001) between LVEI and RVp/pAo ratio. ROC analysis demonstrated an area under the curve = 0.91 for prediction of RVp/pAo >0.50 by the LVEI. An LVEI >1.48 had a sensitivity of 76 % and specificity of 100 % in predicting RVp/pAo >0.50, while an LVEI >1.24 had a sensitivity of 88 % and specificity of 83 %. Echocardiographically derived LVEI is strongly correlated with invasively determined RVp/pAo ratio. In combination with other noninvasive measures of RVp, LVEI may help minimize the need for invasive patient evaluation. PMID- 26667963 TI - Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions. AB - Stereocontrolled formation of carbon-carbon and carbon-heteroatom bonds through asymmetric organocatalysis is a formidable challenge for modern synthetic chemistry. Among the most significant contributions to this field are the transformations involving the use of acetaldehyde or alpha-heteroatom-substituted acetaldehydes for constructing valuable synthons (e.g., amino acid derivatives and hydroxycarbonyl). In this Minireview, versatile (enantioselective) organocatalytic transformations are discussed. PMID- 26667962 TI - Arrhythmias Following Comprehensive Stage II Surgical Palliation in Single Ventricle Patients. AB - Post-operative arrhythmias are common in pediatric patients following cardiac surgery. Following hybrid palliation in single ventricle patients, a comprehensive stage II palliation is performed. The incidence of arrhythmias in patients following comprehensive stage II palliation is unknown. The purpose of this study is to determine the incidence of arrhythmias following comprehensive stage II palliation. A single-center retrospective chart review was performed on all single ventricle patients undergoing a comprehensive stage II palliation from January 2010 to May 2014. Pre-operative, operative, and post-operative data were collected. A clinically significant arrhythmia was defined as an arrhythmia which led to cardiopulmonary resuscitation or required treatment with either pacing or antiarrhythmic medication. Statistical analysis was performed with Wilcoxon rank sum test and Fisher's exact test with p < 0.05 significant. Forty-eight single ventricle patients were reviewed (32 hypoplastic left heart syndrome, 16 other single ventricle variants). Age at surgery was 185 +/- 56 days. Cardiopulmonary bypass time was 259 +/- 45 min. Average vasoactive-inotropic score was 5.97 +/- 7.58. Six patients (12.5 %) had clinically significant arrhythmias: four sinus bradycardia, one 2:1 atrioventricular block, and one slow junctional rhythm. No tachyarrhythmias were documented for this patient population. Presence of arrhythmia was associated with elevated lactate (p = 0.04) and cardiac arrest (p = 0.002). Following comprehensive stage II palliation, single ventricle patients are at low risk for development of tachyarrhythmias. The most frequent arrhythmia seen in these patients was sinus bradycardia associated with respiratory compromise. PMID- 26667961 TI - Echocardiographic Assessment of Right Atrial Pressure in a Pediatric and Young Adult Population. AB - Right atrial pressure (RAP) reflects right-sided cardiac hemodynamics and is useful in management of patients with cardiac and systemic disease. Studies in older adults demonstrated that inferior vena cava (IVC) diameter, IVC collapsibility index, hepatic vein systolic filling fraction (SFF), and right atrial volume (RAV) correlated with mean RAP at catheterization. This study aimed to assess the utility of echocardiographic parameters for assessment of RAP in children and young adults. Patients with pulmonary hypertension or heart transplantation undergoing right heart catheterization were recruited for this prospective observational pilot study. Transthoracic echocardiographic assessment of RAP was performed simultaneously with catheterization. For each parameter, three consecutive cardiac cycles were recorded. Long- and short-axis images of the IVC were obtained. RAV was assessed by area-length and biplane methods. IVC diameters and RAV were indexed to body surface area (BSA)(0.5) and (BSA)(1.4), respectively. Relationships between echocardiographic parameters and mean RAP were correlated using "Pearson's r." Fifty subjects aged 0.3-23 years (median 13, mean 12.3 +/- 7 years) were enrolled. Mean RAP correlated modestly with RAV (r = 0.51, p < 0.001). Long-axis IVCmax (r = 0.30, p < 0.05) and tricuspid E wave velocity (r = 0.36, p < 0.01) also correlated with mean RAP. RV free wall tissue Doppler velocities, IVC collapsibility index, and hepatic vein SFF had no relation to mean RAP. In a pediatric and young adult population with pulmonary hypertension or heart transplantation, echocardiographic assessment of RAV and long-axis IVCmax provided a reasonable estimate of mean RAP. IVC collapsibility index and hepatic vein SFF demonstrated no association with mean RAP. PMID- 26667964 TI - Observation and modeling of conformational molecular structures driving the self assembly of tri-adamantyl benzene on Ag(111). AB - The self-organization of tri-adamantyl (TAB) benzene molecules has been investigated using low temperature scanning tunneling microscopy (LT-STM). The molecular structures have also been studied using molecular modeling. In particular, these calculations have been performed on large areas (1000 nm(2)) from the atomic structure of the molecular building block, combining molecular dynamics (MD) and Monte-Carlo (MC) approaches. These investigations show that the structure of the molecule and its flexibility allow for the formation of different networks as a function of surface coverage. The calculations demonstrate that the stability of the largest structures is obtained through the increase of the interfacial energy induced by the rotation of the adamantyl groups, a behavior whose consequences explain the subtle contrasts observed in the experimental STM images. PMID- 26667965 TI - Potential influence of Gadolinium contrast on image segmentation in MR-based attenuation correction with Dixon sequences in whole-body 18F-FDG PET/MR. AB - OBJECTIVE: To evaluate the influence of Gadolinium contrast agent on image segmentation in magnetic resonance (MR)-based attenuation correction (AC) with four-segment dual-echo time Dixon-sequences in whole-body [18F] fluorodeoxyglucose positron emission tomography (PET)/MR imaging, and to analyze the consecutive effect on standardized uptake value (SUV). MATERIALS AND METHODS: Hybrid imaging with an integrated PET/MR system was performed in 30 oncological patients. AC was based on MR imaging with a Dixon sequence with subsequent automated image segmentation. AC maps (umaps) were acquired and reconstructed prior to (umap-gd) and after (umap+gd) Gd-contrast agent application. For quantification purposes, the SUV of organs and tumors based on both umaps were compared. RESULTS: Tissue classification based on umap-gd was correct in 29/30 patients; based on umap+gd, the brain was falsely classified as fat in 12/30 patients with significant underestimation of SUV. In all cancerous lesions, tissue segmentation was correct. All concordant umaps-gd/+gd resulted in no significant difference in SUV. CONCLUSION: In PET/MR, Gd-contrast agent potentially influences fat/water separation in Dixon-sequences of the head with above-average false tissue segmentation and an associated underestimation of SUV. Thus, MR-based AC should be acquired prior to Gd-contrast agent application. Additionally, integrating the MR-based AC maps into the reading-routine in PET/MR is recommended to avoid interpretation errors in cases where tissue segmentation fails. PMID- 26667967 TI - Rapid and Efficient Separation of Oil from Oil-in-Water Emulsions Using a Janus Cotton Fabric. AB - A novel bi-functional Janus cotton fabric is used to separate oil from oil-in water emulsions. This fabric is superhydrophobic on one surface and polyamine bearing on the other. When used as a filter, the polyamine-bearing side causes the micrometer-sized oil droplets to coalesce. The coalesced oil then fills fabric pores on the superhydrophobic side and selectively permeates it. Oil separation using this method is rapid and the separated oil is pure. Furthermore, the content of the model oil hexadecane (HD) in water after a separation can be reduced to less than 0.03+/-0.03 vol%. These features demonstrate the practical potential of this technology. PMID- 26667966 TI - Performance evaluation of matrix gradient coils. AB - OBJECTIVE: In this paper, we present a new performance measure of a matrix coil (also known as multi-coil) from the perspective of efficient, local, non-linear encoding without explicitly considering target encoding fields. MATERIALS AND METHODS: An optimization problem based on a joint optimization for the non-linear encoding fields is formulated. Based on the derived objective function, a figure of merit of a matrix coil is defined, which is a generalization of a previously known resistive figure of merit for traditional gradient coils. RESULTS: A cylindrical matrix coil design with a high number of elements is used to illustrate the proposed performance measure. The results are analyzed to reveal novel features of matrix coil designs, which allowed us to optimize coil parameters, such as number of coil elements. A comparison to a scaled, existing multi-coil is also provided to demonstrate the use of the proposed performance parameter. CONCLUSIONS: The assessment of a matrix gradient coil profits from using a single performance parameter that takes the local encoding performance of the coil into account in relation to the dissipated power. PMID- 26667968 TI - Interfacial valence electron localization and the corrosion resistance of Al-SiC nanocomposite. AB - Microstructural inhomogeneity generally deteriorates the corrosion resistance of materials due to the galvanic effect and interfacial issues. However, the situation may change for nanostructured materials. This article reports our studies on the corrosion behavior of SiC nanoparticle-reinforced Al6061 matrix composite. It was observed that the corrosion resistance of Al6061 increased when SiC nanoparticles were added. Overall electron work function (EWF) of the Al-SiC nanocomposite increased, along with an increase in the corrosion potential. The electron localization function of the Al-SiC nanocomposite was calculated and the results revealed that valence electrons were localized in the region of SiC-Al interface, resulting in an increase in the overall work function and thus building a higher barrier to hinder electrons in the nano-composite to participate in corrosion reactions. PMID- 26667969 TI - To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt. AB - Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing. PMID- 26667971 TI - Drug therapy: Preclinical oncology - reporting transparency needed. PMID- 26667972 TI - Genetics: Intratumour heterogeneity - a game of snakes and ladders. PMID- 26667973 TI - Colorectal and gastric cancer in 2015: The development of new agents and molecular classifications. PMID- 26667974 TI - Chemotherapy: NAPOLI-1: winning scoop for metastatic pancreatic cancer. PMID- 26667976 TI - Liver cancer: Treatment choice - size matters. PMID- 26667975 TI - Clinical relevance of host immunity in breast cancer: from TILs to the clinic. AB - The clinical relevance of the host immune system in breast cancer has long been unexplored. Studies developed over the past decade have highlighted the biological heterogeneity of breast cancer, prompting researchers to investigate whether the role of the immune system in this malignancy is similar across different molecular subtypes of the disease. The presence of high levels of lymphocytic infiltration has been consistently associated with a more-favourable prognosis in patients with early stage triple-negative and HER2-positive breast cancer. These infiltrates seem to reflect favourable host antitumour immune responses, suggesting that immune activation is important for improving survival outcomes. In this Review, we discuss the composition of the immune infiltrates observed in breast cancers, as well as data supporting the clinical relevance of host antitumour immunity, as represented by lymphocytic infiltration, and how this biomarker could be used in the clinical setting. We also discuss the rationale for enhancing immunity in breast cancer, including early data on the efficacy of T-cell checkpoint inhibition in this setting. PMID- 26667977 TI - Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy. AB - Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcERI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcERI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities. PMID- 26667978 TI - Long-term efficacy and safety of bronchial thermoplasty in patients with moderate to severe persistent asthma: reproducing the same mistake. PMID- 26667979 TI - Immunotherapy in Tumors. AB - BACKGROUND: A number of new drugs for tumor immunotherapy have been approved in the past few years. They work by activating T cells to combat tumors. METHODS: This review is based on publications on recently approved T-cell-activating drugs that were retrieved by a selective search in PubMed. RESULTS: Randomized, controlled trials of "checkpoint" inhibitors, i.e., inhibitory antibodies for use against tumors, have shown that the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab can prolong the survival of patients with advanced melanoma by 2 to 4 months. No data on median overall survival are yet available for the two programmed-death-1 (PD-1) inhibitors pembrolizumab und nivolumab; the endpoint "tumor response" was achieved in 24% and 32% of patients receiving these drugs, respectively. Grade 3 or 4 adverse effects occurred in 50% of patients receiving ipilimumab and in 12 to 13% of those taking either of the two PD-1 inhibitors. Nivolumab prolonged the median survival of patients with metastatic non-small-cell lung cancer from 6 to 9 months. In refractory or recurrent Philadelphia-chromosome-negative pre-B acute lymphoblastic leukemia (pre-B-ALL), treatment with the bispecific antibody construct blinatumomab led to complete remission in 43% of the patients, while grade 3, 4 or 5 toxicities occurred in 83%. CONCLUSION: T-cell-directed strategies have been established as a new pillar of treatment in medical oncology. As these drugs have frequent and severe adverse effects, therapeutic decision-making will have to take account not only of the predicted prolongation of survival, but also of the potential for an impaired quality of life while the patient is under treatment. PMID- 26667980 TI - Fenestrated and Branched Aortic Grafts. AB - BACKGROUND: Abdominal and thoracic aortic aneurysms are diagnosed in 40 and 10 to 15 out of 100 000 persons per year, respectively. Fenestrated (fEVAR) and branched (bEVAR) stent grafts have been developed for abdominal juxtarenal and thoracoabdominal aneurysms. We discuss the patency and complication rates of fEVAR and bEVAR procedures and compare them with the outcome of open surgery. METHODS: This review is based on pertinent publications from 2011 to 2014 that were retrieved by a selective literature search. The clinical outcomes of case series involving a total of more than 1500 patients are presented. The discussion takes account of recommendations contained in the literature and the authors' own experience. RESULTS: Open surgery and aortic stent grafting have not been compared in any randomized trial to date. We identified 7 clinical series that included a total of 1270 fEVAR patients and 5 with a total of 408 bEVAR patients. The perioperative mortality after fEVAR procedures was 0-4%. Spinal cord ischemia arose in 1% of cases. The stent patency rate in visceral vessels ranged from 93 to 98%. bEVAR procedures were associated with both higher mortality (4-7%) and more common spinal cord ischemia (4-13%). 5-8% of all patients needed dialysis perioperatively, and the stent patency rate in visceral vessels was 94-97%. Preoperative renal insufficiency was a risk factor for peri-interventional death. Impaired renal function after fEVAR/bEVAR procedures was mainly associated with intermittent lower limb ischemia. CONCLUSION: The results of fEVAR/bEVAR procedures in the last 5 years are similar to those of open surgery. The high postoperative rate of spinal cord ischemia remains a serious problem in the endovascular treatment of thoracoabdominal aortic aneurysms. The decision to implant a stent graft by an endovascular approach or to treat surgically should be made on a case-to-case basis in an interdisciplinary vascular conference. PMID- 26667981 TI - Quantifying heterogeneous responses of fish community size structure using novel combined statistical techniques. AB - To understand changes in ecosystems, the appropriate scale at which to study them must be determined. Large marine ecosystems (LMEs) cover thousands of square kilometres and are a useful classification scheme for ecosystem monitoring and assessment. However, averaging across LMEs may obscure intricate dynamics within. The purpose of this study is to mathematically determine local and regional patterns of ecological change within an LME using empirical orthogonal functions (EOFs). After using EOFs to define regions with distinct patterns of change, a statistical model originating from control theory is applied (Nonlinear AutoRegressive Moving Average with eXogenous input - NARMAX) to assess potential drivers of change within these regions. We have selected spatial data sets (0.5 degrees latitude * 1 degrees longitude) of fish abundance from North Sea fisheries research surveys (spanning 1980-2008) as well as of temperature, oxygen, net primary production and a fishing pressure proxy, to which we apply the EOF and NARMAX methods. Two regions showed significant changes since 1980: the central North Sea displayed a decrease in community size structure which the NARMAX model suggested was linked to changes in fishing; and the Norwegian trench region displayed an increase in community size structure which, as indicated by NARMAX results, was primarily linked to changes in sea-bottom temperature. These regions were compared to an area of no change along the eastern Scottish coast where the model determined the community size structure was most strongly associated to net primary production. This study highlights the multifaceted effects of environmental change and fishing pressures in different regions of the North Sea. Furthermore, by highlighting this spatial heterogeneity in community size structure change, important local spatial dynamics are often overlooked when the North Sea is considered as a broad-scale, homogeneous ecosystem (as normally is the case within the political Marine Strategy Framework Directive). PMID- 26667982 TI - Macrophage Phenotype Is Associated With the Regenerative Response in Experimental Replacement of the Porcine Esophagus. AB - A porcine model for bridging circumferential defects in the intrathoracic esophagus has been developed in order to improve the treatment of children born with long-gap esophageal atresia. The aim of this study was to identify factors beneficial for tissue regeneration in the bridging area in this model and to describe the histological progression 20 days after replacement with a silicone stented Biodesign mesh. Resection of 3 cm of intrathoracic esophagus and replacement with a bridging graft was performed in six newly weaned piglets. They were fed through a gastrostomy for 10 days, and then had probe formula orally for another 10 days prior to sacrifice. Two out of six piglets had stent loss prior to sacrifice. In the four piglets with the stent in place, a tissue tube, with visible muscle in the wall, was seen at sacrifice. Histology showed that the wall of the healing area was well organized with layers of inflammatory cells, in growing vessels, and smooth muscle cells. CD163+ macrophages was seen toward the esophageal lumen. In the animals where the stent was lost, the bridging area was narrow, and histology showed a less organized structure in the bridging area without the presence of CD163+ macrophages. This study indicates that regenerative healing was seen in the porcine esophagus 20 days after replacement of a part of the intrathoracic esophagus with a silicone-stented Biodesign mesh, if the bridging graft is retained. If the graft is lost, the inflammatory pattern changes with invasion of proinflammatory, M1 macrophages in the entire wall, which seems to redirect the healing process toward scar formation. PMID- 26667983 TI - gammaH2AX expression in cytological specimens as a biomarker of response to radiotherapy in solid malignancies. AB - Many anticancer treatments, including radiotherapy, act by damaging DNA and hindering cell function and proliferation. H2AX is a histone protein directly associated with DNA that is phosphorylated to produce gammaH2AX that accumulates in foci in an early response to DNA double-strand breaks, the most deleterious lesion caused by anticancer therapy. This study reports a gammaH2AX detection assay that has the potential to be used as a biomarker of response to guide cancer treatment. gammaH2AX immunostaining was applied to tumour cell specimens obtained using fine needle aspiration (FNA). Liquid-based cytology and direct smear cytology methods were evaluated and immunostaining protocols established using FNA samples from five cancer patients. The assay was then applied to three patients before and after radiotherapy. Results demonstrate induction of gammaH2AX foci following treatment, persisting for as long as one week after therapy. Immunostaining for gammaH2AX has been successfully applied to FNA samples, providing an opportunity to evaluate gammaH2AX as a treatment response marker in cancer. PMID- 26667984 TI - Vascular cognitive impairment: Biomarkers in diagnosis and molecular targets in therapy. PMID- 26667985 TI - Risk factors for locoregional relapse after transoral robotic surgery for human papillomavirus-related oropharyngeal squamous cell carcinoma. AB - BACKGROUND: Factors predicting locoregional relapse after surgery for oropharyngeal squamous cell carcinoma (SCC) were identified in the pre-human papillomavirus (HPV) era. We examined whether traditional indications for adjuvant radiotherapy (RT) or adjuvant chemoradiotherapy (CRT) still correlate with locoregional relapse in HPV-positive patients after transoral robotic surgery (TORS). METHODS: Retrospective review of oropharyngeal SCC cases identified patients with HPV-positive tumors who did not receive adjuvant therapy after TORS despite intermediate or high-risk features. RESULTS: Median follow-up was 26.7 months (range, 4.9-73.1 months). Five of 25 eligible patients (20%) relapsed at a median 4.8 months (range, 3.2-7.8 months). Two of 18 (11%) intermediate and 3 of 7 (43%) high-risk patients relapsed. Kaplan-Meier 2-year locoregional relapse-free survival estimates for intermediate and high-risk patients were 88% and 57% (p = .078), respectively. CONCLUSION: Traditional indications for adjuvant RT or CRT were associated with high risk of locoregional relapse in HPV-positive patients treated with TORS alone. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1674-E1679, 2016. PMID- 26667986 TI - TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas. AB - CONTEXT: TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). OBJECTIVE: We investigated the association between TERT promoter mutations and survival from PTC. DESIGN: Retrospective observational cohort study. PATIENTS: Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. MEASUREMENTS: TERT promoter was genotyped in DNA from 80 archival PTCs by Sanger sequencing. Median follow-up was 106 months (range 1-270). Outcomes analysis was stratified according to disease and overall survival status. For each parameter, relative risk (RR) adjusted for age at first surgery and gender was estimated. Both univariate and multivariate analyses were performed using logistic regression, Kaplan-Meier survival analysis and Cox regression models. RESULTS: PTCs from 11 patients (14%) contained either C228T or C250T TERT promoter mutation. TERT mutations were significantly associated with adverse prognostic features such as older age (P = 0.002), male gender (P = 0.01) and Stage IV disease (P = 0.03). Four patients died from PTC during follow-up: 3 patients with TERT mutations (27%) and one without (1.5%). Disease-related mortality rate with or without TERT mutations was 33.7 vs 1.6 per 1000 patient-years respectively, that is 10 (95% CI = 1.0-104.1, P = 0.05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF(V) (600E) significantly increased disease-related death risk (P = 0.002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF(V) (600E) . CONCLUSIONS: TERT promoter mutations are a major indicator of death due to PTCs. Conversely, absence of TERT mutations portends better survival. PMID- 26667987 TI - Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE. AB - We examined the influence of neighborhood socioeconomic position (SEP), racial/ethnic composition, and living in a major city on cognitive trajectories and intervention outcomes. Data came from the Advanced Cognitive Training for Independent and Vital Elderly study ( N = 2,438). Mixed effects analyses examined the associations between neighborhood variables and memory, reasoning, speed of processing, and everyday cognition, estimating differences in initial gains (potentially related to practice) and long-term rate of change over 10 years. The effect of reasoning training on initial gain was weaker for individuals in a major city. For everyday cognition, there was a stronger initial gain for memory trained and control participants in areas with more racial/ethnic minorities and for speed-trained and control individuals in higher SEP areas. The racial/ethnic minority effect was no longer significant after adjustment for multiple comparisons. Neighborhood factors may be more important in practice-related improvement than in long-term change. PMID- 26667989 TI - Ba(1-x)Sr(x)Zn2Si2O7--A new family of materials with negative and very high thermal expansion. AB - The compound BaZn2Si2O7 shows a high coefficient of thermal expansion up to a temperature of 280 degrees C, then a transition to a high temperature phase is observed. This high temperature phase exhibits negative thermal expansion. If Ba(2+) is successively replaced by Sr(2+), a new phase with a structure, similar to that of the high temperature phase of BaZn2Si2O7, forms. At the composition Ba0.8Sr0.2Zn2Si2O7, this new phase is completely stabilized. The crystal structure was determined with single crystal X-ray diffraction using the composition Ba0.6Sr0.4Zn2Si2O7, which crystallizes in the orthorhombic space group Cmcm. The negative thermal expansion is a result of motions and distortions inside the crystal lattice, especially inside the chains of ZnO4 tetrahedra. Dilatometry and high temperature X-ray powder diffraction were used to verify the negative thermal expansion. Coefficients of thermal expansion partially smaller than -10.10(-6) K(-1) were measured. PMID- 26667988 TI - Aspergillus Vertebral Osteomyelitis Complicating Pulmonary Granuloma in an Immunocompetent Adult. AB - OBJECTIVE: The aim of this report is to describe a case with Aspergillus vertebral osteomyelitis complicating pulmonary granuloma in an immunocompetent adult. CLINICAL PRESENTATION AND INTERVENTION: A 53-year-old male patient was found to have lesions on lumbar vertebra 5 months after thoracoscopic resection of pulmonary granuloma that lacked a definite etiology. Three operations on the lumbar lesions were performed successively; however, an Aspergillus infection was not confirmed until hyphae were clearly detected at the last surgery. The patient was treated with voriconazole and recovered well. CONCLUSION: This case shows that simultaneous occurrence of granulomatous nodules in the lung and vertebral lesions should raise suspicion of aspergillosis, even in immunocompetent patients. PMID- 26667990 TI - Circumflex Origin from Right Coronary Artery--The Anomaly That Should Not Be Omitted during Echocardiography--"Crossed Aorta" and "Bleb Sign" Presentation after Stents Implantation. PMID- 26667991 TI - Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression. AB - Cell cycle progression is strictly coordinated to ensure proper tissue growth, development, and regeneration of multicellular organisms. Spatiotemporal visualization of cell cycle phases directly helps us to obtain a deeper understanding of controlled, multicellular, cell cycle progression. The fluorescent ubiquitination-based cell cycle indicator (Fucci) system allows us to monitor, in living cells, the G1 and the S/G2/M phases of the cell cycle in red and green fluorescent colors, respectively. Since the discovery of Fucci technology, it has found numerous applications in the characterization of the timing of cell cycle phase transitions under diverse conditions and various biological processes. However, due to the complexity of cell cycle dynamics, understanding of specific patterns of cell cycle progression is still far from complete. In order to tackle this issue, quantitative approaches combined with mathematical modeling seem to be essential. Here, we review several studies that attempted to integrate Fucci technology and mathematical models to obtain quantitative information regarding cell cycle regulatory patterns. Focusing on the technological development of utilizing mathematics to retrieve meaningful information from the Fucci producing data, we discuss how the combined methods advance a quantitative understanding of cell cycle regulation. PMID- 26667992 TI - Direct Identification of Aerobic Bacteria by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Is Accurate and Robust. AB - BACKGROUND: Bacterial identification in the clinical laboratory can be laborious and expensive. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid and cost-effective diagnostic tool for the identification of organisms routinely found in the microbiology laboratory. The objective of this study was to demonstrate that identification of aerobic Gram positive and Gram-negative organisms could be performed accurately and efficiently by MALDI-TOF MS and the Bruker Biotyper system without the use of time-consuming extraction methodologies. METHODS: Isolates previously recovered by routine culture and workup from clinical specimens were cultured to appropriate media, identified directly by MALDI-TOF MS, and compared to results from various biochemical identification methods. RESULTS: Using the direct-smear method, 99.5% and 98.0% of aerobic Gram-negative and Gram-positive bacteria, respectively, were identified to the genus level. At a score of >=1.9, 97.6% Gram negative organisms and 94.6% Gram-positive organisms were correctly identified to the species level by direct-smear method. Only 1.1% of isolates required further reflex to direct-plate extraction. The direct-smear method proved to be robust, as various growth temperatures, media, culture age, and different operators had no notable impact on the bacterial identification rate. CONCLUSION: The direct smear method is an accurate and time-saving method for routine species-level bacterial identification. PMID- 26667993 TI - Hear me, see me, feel me. PMID- 26667994 TI - Arabinogalactan proteins have deep roots in eukaryotes: identification of genes and epitopes in brown algae and their role in Fucus serratus embryo development. AB - Arabinogalactan proteins (AGPs) are highly glycosylated, hydroxyproline-rich proteins found at the cell surface of plants, where they play key roles in developmental processes. Brown algae are marine, multicellular, photosynthetic eukaryotes. They belong to the phylum Stramenopiles, which is unrelated to land plants and green algae (Chloroplastida). Brown algae share common evolutionary features with other multicellular organisms, including a carbohydrate-rich cell wall. They differ markedly from plants in their cell wall composition, and AGPs have not been reported in brown algae. Here we investigated the presence of chimeric AGP-like core proteins in this lineage. We report that the genome sequence of the brown algal model Ectocarpus siliculosus encodes AGP protein backbone motifs, in a gene context that differs considerably from what is known in land plants. We showed the occurrence of AGP glycan epitopes in a range of brown algal cell wall extracts. We demonstrated that these chimeric AGP-like core proteins are developmentally regulated in embryos of the order Fucales and showed that AGP loss of function seriously impairs the course of early embryogenesis. Our findings shine a new light on the role of AGPs in cell wall sensing and raise questions about the origin and evolution of AGPs in eukaryotes. PMID- 26667995 TI - Neutral Fe(IV) alkylidenes, including some that bind dinitrogen. AB - Neutral, formally Fe(IV) alkylidene species are sought as plausible olefin metathesis catalysts, and the synthesis of several is described herein. The complexes are prepared via nucleophilic attack (Nu = MeLi, PhCH2K, 2 picolyllithium, Me2PCH2Li, MePhPCH2Li, Ph2PCH2Li) at the imine of cationic [mer {kappa-C,N,C-(C6H4-yl)-2-CH=N(2-C6H4-C(iPr)=)}Fe(PMe3)3][B(3,5-CF3-C6H3)4]. In contrast, MeMgCl and mesityllithium displaced and deprotonated bound PMe3, respectively. Structural details are provided for mer-{kappa-C,N,C-(C6H4-yl)-2 CH(Bn)N(2-C6H4-C(iPr))}Fe{trans-(PMe3)2}N2 and {kappa-C,N,C,P-(C6H4-yl)-2 CH(CH2PMe2)N(2-C6H4-C(iPr)=)}Fe(PMe3)2. PMID- 26667996 TI - Reading direction causes spatial biases in mental model construction in language understanding. AB - Correlational evidence suggests that the experience of reading and writing in a certain direction is able to induce spatial biases at both low-level perceptuo motor skills and high-level conceptual representations. However, in order to support a causal relationship, experimental evidence is required. In this study, we asked whether the direction of the script is a sufficiente cause of spatial biases in the mental models that understanders build when listening to language. In order to establish causality, we manipulated the experience of reading a script with different directionalities. Spanish monolinguals read either normal (left-to-right), mirror reversed (right-to-left), rotated downward (up-down), or rotated upward (down-up) texts, and then drew the contents of auditory descriptions such as "the square is between the cross and the triangle". The directionality of the drawings showed that a brief reading experience is enough to cause congruent and very specific spatial biases in mental model construction. However, there were also clear limits to this flexibility: there was a strong overall preference to arrange the models along the horizontal dimension. Spatial preferences when building mental models from language are the results of both short-term and long-term biases. PMID- 26667997 TI - Heart rate variability in elite sprinters: effects of gender and body position. AB - To describe the heart rate variability (HRV) of high-level sprinters in both the supine and standing positions, the HRV of 7 male (24 +/- 6 years; 80 +/- 8 kg and 182 +/- 7 cm) and 11 female (27 +/- 5 years; 61 +/- 4 kg; 167 +/- 5 cm) high level Brazilian sprinters was measured in the standing and supine body positions in both the time and frequency domains. The heart rate (HR) and the time (SDNN, RMSSD) and frequency (LF; HF and LF:HF) domains of the HRV were assessed. Natural log-transformations (ln) of all HRV indices were log-transformed prior to analysis to reduce bias arising from non-uniformity of error. The Cohen's effect size and magnitude-based inference (MBI) were obtained for comparisons. The results suggest higher cardiac autonomic stress in the standing position than in the supine for both genders. With the exception of the lnSDNN that showed possibly MBI in female athletes, all other HRV indices presented a likely or almost certainly MBI. Male athletes demonstrated a higher lnSDNN in the supine body position (very likely MBI) and a higher HR in the standing position (very likely MBI) than females. In conclusion, elite sprinters (independent of the gender) present lower HRV in the standing position than in the supine position, but males present a more notable change in cardiac autonomic stress than female athletes. PMID- 26667999 TI - Antioxidant effect of 1,3,4-thiadiazolium mesoionic derivatives on isolated mitochondria. AB - Mesoionic compounds have shown antitumor and citotoxic activity against different tumor cells lines, which has been attributed to their physical and chemical characteristics. Among these compounds, the 1,3,4-thiadiazolium-2-phenylamine derivatives have been highlighted due to their important anti-melanoma activity. In this work, the effects of three derivatives that belong this class, MI-J, MI 4F and MI-2,4diF, on the oxidative stress parameters were evaluated using rat liver mitochondria. All the derivatives prevented natural and calcium induced oxidation of pyridine nucleotides at lower concentrations (6.5 and 32.5nmol/mg protein). The calcium uptake was inhibited by all the derivatives at higher concentrations (65 and 130nmol/mg protein), whereas the cation efflux was inhibited only by the MI-J (52%) and MI-4F (50%), possibly by inhibiting the formation of the permeability transition pore (PTP) by 100% and 50%, respectively, as observed in the same experimental conditions. MI-2,4diF did not inhibit the mitochondrial permeability transition or calcium efflux. The enzymatic activity of glutathione reductase, glutathione peroxidase and catalase was not affected by any derivative, but superoxide dismutase was inhibited by all the derivatives. MI-J inhibited enzyme activity significantly (85%) at the highest concentration (130nmol/mg protein); on the other hand, their activity was less affected by fluorine derivatives (MI-4F-20% and MI-2,4diF-32%). These results suggest that these derivatives exert antioxidant effects on isolated mitochondria. PMID- 26668000 TI - Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. AB - Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1beta, TNF-alpha, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1beta and TNF-alpha production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1beta and TNF-alpha expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. PMID- 26668001 TI - Modern Separation Techniques for the Isolation of Natural Products. PMID- 26668002 TI - destiny: diffusion maps for large-scale single-cell data in R. AB - : Diffusion maps are a spectral method for non-linear dimension reduction and have recently been adapted for the visualization of single-cell expression data. Here we present destiny, an efficient R implementation of the diffusion map algorithm. Our package includes a single-cell specific noise model allowing for missing and censored values. In contrast to previous implementations, we further present an efficient nearest-neighbour approximation that allows for the processing of hundreds of thousands of cells and a functionality for projecting new data on existing diffusion maps. We exemplarily apply destiny to a recent time-resolved mass cytometry dataset of cellular reprogramming. AVAILABILITY AND IMPLEMENTATION: destiny is an open-source R/Bioconductor package "bioconductor.org/packages/destiny" also available at www.helmholtz muenchen.de/icb/destiny A detailed vignette describing functions and workflows is provided with the package. CONTACT: carsten.marr@helmholtz-muenchen.de or f.buettner@helmholtz-muenchen.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26668003 TI - Fuse: multiple network alignment via data fusion. AB - MOTIVATION: Discovering patterns in networks of protein-protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. However, the complexity of the multiple network alignment problem grows exponentially with the number of networks being aligned and designing a multiple network aligner that is both scalable and that produces biologically relevant alignments is a challenging task that has not been fully addressed. The objective of multiple network alignment is to create clusters of nodes that are evolutionarily and functionally conserved across all networks. Unfortunately, the alignment methods proposed thus far do not meet this objective as they are guided by pairwise scores that do not utilize the entire functional and evolutionary information across all networks. RESULTS: To overcome this weakness, we propose Fuse, a new multiple network alignment algorithm that works in two steps. First, it computes our novel protein functional similarity scores by fusing information from wiring patterns of all aligned PPI networks and sequence similarities between their proteins. This is in contrast with the previous tools that are all based on protein similarities in pairs of networks being aligned. Our comprehensive new protein similarity scores are computed by Non-negative Matrix Tri-Factorization (NMTF) method that predicts associations between proteins whose homology (from sequences) and functioning similarity (from wiring patterns) are supported by all networks. Using the five largest and most complete PPI networks from BioGRID, we show that NMTF predicts a large number protein pairs that are biologically consistent. Second, to identify clusters of aligned proteins over all networks, Fuse uses our novel maximum weight k-partite matching approximation algorithm. We compare Fuse with the state of the art multiple network aligners and show that (i) by using only sequence alignment scores, Fuse already outperforms other aligners and produces a larger number of biologically consistent clusters that cover all aligned PPI networks and (ii) using both sequence alignments and topological NMTF-predicted scores leads to the best multiple network alignments thus far. AVAILABILITY AND IMPLEMENTATION: Our dataset and software are freely available from the web site: http://bio nets.doc.ic.ac.uk/Fuse/ CONTACT: natasha@imperial.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26668004 TI - Positive and negative forms of replicability in gene network analysis. AB - MOTIVATION: Gene networks have become a central tool in the analysis of genomic data but are widely regarded as hard to interpret. This has motivated a great deal of comparative evaluation and research into best practices. We explore the possibility that this may lead to overfitting in the field as a whole. RESULTS: We construct a model of 'research communities' sampling from real gene network data and machine learning methods to characterize performance trends. Our analysis reveals an important principle limiting the value of replication, namely that targeting it directly causes 'easy' or uninformative replication to dominate analyses. We find that when sampling across network data and algorithms with similar variability, the relationship between replicability and accuracy is positive (Spearman's correlation, rs ~0.33) but where no such constraint is imposed, the relationship becomes negative for a given gene function (rs ~ 0.13). We predict factors driving replicability in some prior analyses of gene networks and show that they are unconnected with the correctness of the original result, instead reflecting replicable biases. Without these biases, the original results also vanish replicably. We show these effects can occur quite far upstream in network data and that there is a strong tendency within protein protein interaction data for highly replicable interactions to be associated with poor quality control. AVAILABILITY AND IMPLEMENTATION: Algorithms, network data and a guide to the code available at: https://github.com/wimverleyen/AggregateGeneFunctionPrediction CONTACT: jgillis@cshl.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26668005 TI - DNAshapeR: an R/Bioconductor package for DNA shape prediction and feature encoding. AB - DNAshapeR predicts DNA shape features in an ultra-fast, high-throughput manner from genomic sequencing data. The package takes either nucleotide sequence or genomic coordinates as input and generates various graphical representations for visualization and further analysis. DNAshapeR further encodes DNA sequence and shape features as user-defined combinations of k-mer and DNA shape features. The resulting feature matrices can be readily used as input of various machine learning software packages for further modeling studies. AVAILABILITY AND IMPLEMENTATION: The DNAshapeR software package was implemented in the statistical programming language R and is freely available through the Bioconductor project at https://www.bioconductor.org/packages/devel/bioc/html/DNAshapeR.html and at the GitHub developer site, http://tsupeichiu.github.io/DNAshapeR/ CONTACT: rohs@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26668006 TI - Trimetazidine improves exercise tolerance in patients with ischemic heart disease : A meta-analysis. AB - AIM: This study aimed to evaluate the effect of trimetazidine (TMZ) in addition to standard treatment on exercise tolerance in patients with ischemic heart disease (IHD). METHODS: Studies were identified via a systematic search of PubMed, Embase, Cochrane Library, and the Chinese CNKI databases from January 1978 to January 2015. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Random or fixed effects models were used to estimate pooled mean differences in total exercise duration (TED), peak oxygen uptake (pVO2), metabolic equivalent system (METS), and 6-minute walking test (6-MWT). RESULTS: In all, 16 randomized controlled trials (RCTs) consisting of 2,004 participants were included. Pooled results showed that TMZ treatment significantly improved TED (WMD: 37.35, 95 % CI: 25.58-49.13, p < 0.00001), pVO2 (WMD: 2.41, 95 % CI: 1.76-3.06, p < 0.00001), METS (WMD: 1.33, 95 % CI: 0.38 2.28, p = 0.006), and 6-WMT (WMD: 62.46, 95 % CI: 35.86-89.05, p < 0.001) in all patients with IHD. Subgroup analysis showed that TMZ significantly increased TED in nondiabetic participants (WMD 34.77, 95 % CI: 22.28-47.25, p < 0.001), but not in diabetic participants (WMD: 40.36, 95 % CI: - 18.76-99.48, p = 0.18). And, subgroup analysis of TED by intervention duration suggested that there is no statistically difference between the 3-month and 6-month periods (WMD: 35.47, 95 %CI: 18.35-52.60, p < 0.0001 and WMD: 49.94, 95 %CI: 44.69-55.19, p < 0.00001). In addition, TMZ improved TED (WMD: 50.01, 95 % CI: 44.77-55.25 and WMD: 24.20, 95 % CI: 12.72-35.68) in IHD patients with or without heart failure (HF), respectively. CONCLUSION: Addition of TMZ to standard treatment significantly improved exercise tolerance in patients with IHD, and IHD patients with HF may experience even more benefits. However, there is insufficient evidence to show that TMZ has beneficial effects in participants with diabetes. PMID- 26668007 TI - Analysis of 24 Y-STR haplotype data in a Chinese Han population from Guangdong Province. AB - In this study, we investigated the genetic polymorphisms of 24 Y-chromosomal short tandem repeat (Y-STR) loci in 885 unrelated Chinese Han male individuals from Guangdong Province, using a domestic AGCU Y24 STR kit. A total of 878 different haplotypes were observed at the 24 Y-STR loci; among them, 871 haplotypes were unique and 7 haplotypes occurred twice. The overall haplotype diversity was 0.99998 and the discrimination capacity was 99.2%. The gene diversity values ranged from 0.4354 at DYS438 to 0.9606 at DYS385a/b. Population relationships between the Guangdong Han population and seven other published Chinese populations were evaluated by Rst values and visualized in a two multi dimensional scaling plot. The results showed the 24 Y-STR loci are highly polymorphic in Guangdong Han population and of great value in forensic application. PMID- 26668008 TI - Stigma Related Avoidance in People Living with Severe Mental Illness (SMI): Findings of an Integrative Review. AB - The purpose of this integrative review is to synthesize primary evidence of the impact of internalized stigma on avoidance in adult community treatment patients living with SMI. A keyword database search of articles published through 2015 yielded 21 papers and a total of 4256 patients. Our analyses found that stigmatizing beliefs associated with avoidance are related to significant loss of self-esteem. Factors generally thought to reduce stigma internalized as self stigmatizing beliefs, such as improved insight, increased self-awareness, and psycho-education to improve stigma coping skills, do not appear to improve self esteem. PMID- 26668009 TI - Mining candidate genes associated with powdery mildew resistance in cucumber via super-BSA by specific length amplified fragment (SLAF) sequencing. AB - BACKGROUND: Powdery mildew (PM) is the most common fungal disease of cucumber and other cucurbit crops, while breeding the PM-resistant materials is the effective way to defense this disease, and the recent development of modern genetics and genomics make us aware of that studying the resistance genes is the essential way to breed the PM high-resistance plant. With the ever increasing throughput of next-generation sequencing (NGS), the development of specific length amplified fragment sequencing (SLAF-seq) as a high-resolution strategy for large-scale de novo SNP discovery is gradually applied for functional gene mining. Here we combined the bulked segregant analysis (BSA) with SLAF-seq to identify candidate genes associated with PM resistance in cucumber. METHODS: A segregating population comprising 251 F2 individuals was developed using H136 (female parent) as susceptible parent and BK2 (male parent) as resistance donor. After PMR test, total genomic DNA was prepared from each plant. Systemic genomic analysis of the GC content, repeat sequence, etc. was carried out by prediction software SLAF_Predict to establish condition to ensure the uniformity and density of the molecular markers. After samples were gel purified, SLAFs were generated at Biomarker Technologies Corporation in Beijing. Based on SLAF tags and the PMR test result, the hot region were annotated. RESULTS: A total of 73,100 high quality SLAF tags with an average depth of 99.11* were sequenced. Among these, 5,355 polymorphic tags were identified with a polymorphism rate of 7.34 %, including 7.09 % SNPs and other polymorphism types. Finally, 140 associated SLAFs were identified, and two main Hot Regions were detected on chromosome 1 and 6, which contained five genes invovled in defense response, toxin metabolism, cell stress response, and injury response in cucumber. CONCLUSIONS: Associated markers identified by super-BSA in this study, could not only speed up the study of the PMR genes, but also provide a feasible solution for breeding the marker-assisted PMR cucumber. Moreover, this study could also be extended to any other species with reference genome. PMID- 26668010 TI - Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress. AB - Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID- 26668011 TI - Serotonin release in the central nucleus of the amygdala in response to noxious and innocuous cutaneous stimulation in anesthetized rats. AB - We investigated the effect of noxious (pinching) and innocuous (stroking) stimulation of skin on serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. 5-HT in the CeA was collected by microdialysis methods. Dialysate output from consecutive 10-min periods was injected into a high-performance liquid chromatograph and 5-HT was measured with an electrochemical detector. Bilateral pinching of the back for 10 min increased 5-HT release significantly; 5-HT release was also increased with stimulation of the forelimb or hindlimb. In contrast, stroking of these areas decreased 5-HT release significantly. Furthermore, simultaneous stroking and pinching produced no change in the 5-HT release. In conclusion, the present study demonstrates that 5-HT release in the CeA is regulated by somatic afferent stimulation in a modality-dependent manner, and that innocuous stimulation can dampen the change in 5-HT release that occurs in response to noxious stimulation. PMID- 26668012 TI - Coordination Polymers of Palladium Bridged by Carboxylate and Dimethylaminoalkylselenolate Ligands. AB - Coordination polymers of palladium stabilized by dimethylaminoalkylselenolate and carboxylate ligands are reported. The reaction of [PdCl(SeCH2 CH2 NMe2 )]3 with AgOTf followed by treatment with sodium acetate afforded [Pd(0) Pd(II) 4 (SeCH2 CH2 NMe2 )3 (OAc)3 ](OTf)2 (1) in which one of the Pd atoms is in the zero oxidation state. In the absence of NaOAc, a tetranuclear complex, [Pd(II) 4 (SeCH2 CH2 NMe2 )4 (OTf)](OTf)3 (2), is isolated from the same reaction. Subsequent treatment with NaO2 CR afforded [Pd4 (SeCH2 CH2 NMe2 )4 (O2 CR)4 ] (R=tBu (3) and Ph (4)). The reaction of [PdCl(SeCH2 CH2 CH2 NMe2 )]2 with AgOTf and NaOAc yielded an ionic binuclear complex, [Pd(II) 2 (SeCH2 CH2 CH2 NMe2 )2 (OAc)](OTf) (5). These complexes have been characterized by NMR spectroscopy, crystal structures, and in some cases by X-ray photoelectron spectroscopy, cyclic voltammetry and mass spectrometry. Complexes 1 and 5 are associated through secondary interactions and coordinate bonds, respectively, to generate polymeric structures in the solid state. PMID- 26668013 TI - Smoking and progression of diabetic nephropathy in patients with type 1 diabetes. AB - AIMS: To evaluate the effect of cumulative smoking on the development of diabetic nephropathy. METHODS: Study included 3613 patients with type 1 diabetes, participating in the Finnish Diabetic Nephropathy Study. The 12-year cumulative risk of microalbuminuria, macroalbuminuria and end-stage renal disease (ESRD) was estimated for current, ex- and nonsmokers. Cox regression analyses, with multivariable adjustments for other risk factors for diabetic nephropathy, were used to evaluate the risk at different stages of diabetic nephropathy based on the cumulative amount of smoking in pack-years. RESULTS: The 12-year cumulative risk of microalbuminuria was 18.9 % (95 % CI 14.6-23.0, P < 0.0001) for current smokers and 15.1 % (10.3-19.6, P = 0.087) for ex-smokers, compared with 10.0 % (7.8-12.1) for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % (95 % CI 10.8-17.9, P < 0.0001), 6.1 % (3.5-8.6, P = 0.082) and 4.7 % (3.0 6.4), respectively. The 12-year cumulative risk of ESRD was 10.3 % (95 % CI 8.4 12.4, P < 0.0001) for current smokers and 10.0 % (7.9-12.3, P < 0.0001) for ex smokers, compared with 5.6 % (4.6-6.7) for nonsmokers. In the current smokers, one pack-year increased the risk of macroalbuminuria with a HR of 1.025 (1.010 1.041) and the risk of ESRD with a HR of 1.014 (1.001-1.026) compared with nonsmokers, in the fully adjusted model. In the ex-smokers, the risk of macroalbuminuria and ESRD was no different from the risk in nonsmokers after multivariable adjustment. CONCLUSIONS: Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers. PMID- 26668015 TI - The investigation into the cutaneous silent period in patients with essential tremor pre-treatment and post-treatment. AB - Although essential tremor (ET) is the most common movement disorder, little is known regarding its pathophysiology. Cutaneous silent period (CSP) is a spinal inhibitory reflex that causes suppression of the voluntary muscle contraction that is induced by strong electrical stimulation of the cutaneous nerves. Clinical interest in the CSP stems from its potential usefulness for evaluating segment and components of sensory nerves that are not well assessed by standard electrodiagnostic methods. The aim of this study was to investigate CSP in patients with ET before and after treatment. A total of 30 patients (12 females + 18 males), having ET diagnosis and propranolol treatment initiated, were studied with technique of CSP. Patient group's pre-treatment latency average is found 84.45 +/- 18.63, average CSP duration 42.37 +/- 11.82, and CSP final latency average 127.10 +/- 19.13. According to post-treatment CSP analysis, it is seen that patients' average latency values are found 83.14 +/- 20.92 and it is determined that there is no significant statistical difference compared to pre treatment latency values (p > 0.05). Post-treatment average CSP duration is found 36.64 +/- 13.38, and it is seen that there is a significant statistical shortening compared to pre-treatment durations (p < 0.05). Patients' post treatment CSP final latency averages are found 123.17 +/- 13.67, and it is determined that there is no significant statistical difference compared to pre treatment latency values (p > 0.05). The main finding of this study is that in ET the CSP is prolonged and that treatment with propranolol shortens the CSP and brings it closer to normal values. A small dose of propranolol has the effect of shortening pathologically prolonged CSP in a subset of ET patients (women and without family history), making further investigations with this method interesting. From this point of view in our study, patients with ET treatment give an idea of the effectiveness of propranolol. In recent years, a technique of CSP is interested in the field of electrophysiology and shows the effect of ET that given other pharmacological treatment and also it can be considered a quantitative measure to compare them. The usefulness of CSP should be supported by further studies with more patients. PMID- 26668014 TI - Extracellular Matrix and Regenerative Therapies from the Cardiac Perspective. AB - Cardiovascular diseases are the leading cause of death and a major cause of financial burden. Regenerative therapies for heart diseases bring the promise of alternative treatment modalities for myocardial infarction, ischemic heart disease, and congestive heart failure. Although, clinical trials attest to the safety of stem cell injection therapies, researchers need to overcome the underlying mechanisms that are limiting the success of future regenerative options. This article aims to review the basic scientific concepts in the field of mechanobiology and the effects of extracellular functions on stem cell fate. PMID- 26668016 TI - Isolated facial sensory loss due to thalamic lacunar infarction. PMID- 26668017 TI - Evaluation of a Multimedia Intervention for Children and Families Facing Multiple Military Deployments. AB - Repeated military deployments have been a common experience for many military families in the past 15 years. While there has been an increase in research and intervention focused on the effects on families of military deployments, much of this work has not focused specifically on the particular needs of young children. Talk, Listen, Connect: Multiple Deployments (TLC-II MD), a multimedia kit designed for home use, is among the first interventions directed toward young children. Created by Sesame Workshop and using popular Sesame Street characters, TLC-II MD was designed to support and equip families with young children with skills to address challenges associated with multiple deployments. This study utilized a randomized experimental design to evaluate the impact of TLC-II MD relative to a control condition using a Sesame Workshop multimedia kit not tailored to military families. Parents in both groups reported that children enjoyed the video overall and watched it repeatedly. Also in both groups, caregivers' depressive symptoms and children's aggressive behaviors declined significantly over time. Caregivers in the test group reported significantly larger increases in comfort discussing the deployment with their child and stronger perceptions that the DVD helped children to cope. Thus, the resilience oriented materials were helpful to both groups, but those tailored to military families were significantly more likely to be perceived as helpful. Findings offer evidence regarding the ability of multimedia self-administered interventions to assist military families. PMID- 26668018 TI - The 2015 Albert Lasker Basic Medical Research Award: An exhilarating journey to the DNA damage checkpoint. PMID- 26668019 TI - The discovery of Qinghaosu (artemisinin) as an effective anti-malaria drug: A unique China story. PMID- 26668020 TI - Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD. AB - BACKGROUND AND OBJECTIVES: eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromso Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR. RESULTS: sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to 0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to 0.1 per SD increase in log CRP). CONCLUSIONS: eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies. PMID- 26668021 TI - Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension. AB - BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) and abnormal left ventricular (LV) geometry predict adverse outcomes in the general and hypertensive populations, but findings in CKD are still inconclusive. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled 445 patients with hypertension and CKD stages 2-5 in two academic nephrology clinics in 1999-2003 who underwent both echocardiography and ambulatory BP monitoring. LVH (LV mass >100 g/m(2) [women] and >131 g/m(2) [men]) and relative wall thickness (RWT) were used to define LV geometry: no LVH and RWT<=0.45 (normal), no LVH and RWT>0.45 (remodeling), LVH and RWT<=0.45 (eccentric), and LVH and RWT>0.45 (concentric). We evaluated the prognostic role of LVH and LV geometry on cardiovascular (CV; composite of fatal and nonfatal events) and renal outcomes (composite of ESRD and all-cause death). RESULTS: Age was 64.1+/-13.8 years old; 19% had diabetes, and 22% had CV disease. eGFR was 39.9+/-20.2 ml/min per 1.73 m(2). LVH was detected in 249 patients (56.0%); of these, 125 had concentric LVH, and 124 had eccentric pattern, whereas 71 patients had concentric remodeling. Age, women, anemia, and nocturnal hypertension were independently associated with both concentric and eccentric LVH, whereas diabetes and history of CV disease associated with eccentric LVH only, and CKD stages 4 and 5 associated with concentric LVH only. During follow-up (median, 5.9 years; range, 0.04-15.3), 188 renal deaths (112 ESRD) and 103 CV events (61 fatal) occurred. Using multivariable Cox analysis, concentric and eccentric LVH was associated with higher risk of CV outcomes (hazard ratio [HR], 2.59; 95% confidence interval [95% CI], 1.39 to 4.84 and HR, 2.79; 95% CI, 1.47 to 5.26, respectively). Similarly, greater risk of renal end point was detected in concentric (HR, 2.33; 95% CI, 1.44 to 3.80) and eccentric (HR, 2.30; 95% CI, 1.42 to 3.74) LVH. Sensitivity analysis using LVH and RWT separately showed that LVH but not RWT was associated with higher cardiorenal risk. CONCLUSIONS: In patients with CKD, LVH is a strong predictor of the risk of poor CV and renal outcomes independent from LV geometry. PMID- 26668023 TI - CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia. AB - BACKGROUND AND OBJECTIVES: Despite the many studies showing an association between CKD and a high risk of ischemic events and mortality, the association of CKD with peripheral arterial disease (PAD) still has not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This large cohort study assessed the association of CKD, even in the earlier stages, with morbidity, short- and long-term outcome, and costs among patients with PAD. RESULTS: We identified 41,882 patients with PAD who had an index hospitalization between January 1, 2009, and December 31, 2011. Of these, 8470 (20.2%) also had CKD (CKD stage 2: n=2158 [26%]; stage 3: n=3941 [47%]; stage 4: n=935 [11%]; stage 5: n=1436 [17%]). The ratio of women to men was 1:1.2. Compared with patients without known CKD, those with CKD had higher frequencies of coronary artery disease (1.8-fold higher; P<0.001), chronic heart failure (3.3-fold higher; P<0.001), and Rutherford PAD categories 5 and 6 (1.8-fold higher; P<0.001); underwent significantly fewer revascularizations (0.9-fold fewer; P<0.001); had a nearly two-fold higher amputation rate (P<0.001); had higher frequencies of in-hospital infections (2.1-fold higher; P<0.001), acute renal failure (2.8-fold higher; P<0.001), and sepsis (1.9-fold higher; P<0.001); had a 2.5-fold higher frequency of myocardial infarction (P<0.001); and had a nearly three-fold higher in hospital mortality rate (P<0.001). In an adjusted multivariable Cox regression model, CKD remained a significant predictor of long-term outcome of patients with PAD during follow-up for up to 4 years (until December 31, 2012; median, 775 days; 25th-75th percentiles, 469-1120 days); the hazard ratio was 2.59 (95% confidence interval, 2.21 to 2.78; P<0.001). The projected mortality rates after 4 years were 27% in patients without known CKD and 46%, 52%, 72%, and 78% in those with CKD stages 2, 3, 4, and 5, respectively. Lengths of hospital stay and reimbursement costs were on average nearly 1.4-fold higher (P<0.001) in patients who also had CKD. CONCLUSIONS: This analysis illustrates the significant and important association of CKD with in-hospital and long-term mortality, morbidity, amputation rates, duration and costs of hospitalization, in-hospital treatment, and complications in patients with PAD. PMID- 26668022 TI - Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKD. AB - BACKGROUND AND OBJECTIVES: Ultrasonographic detection of subclinical atheromatosis is a noninvasive method predicting cardiovascular events. Risk factors predicting atheromatosis progression in CKD are unknown. Predictors of atheromatosis progression were evaluated in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our multicenter, prospective, observational study included 1553 patients with CKD (2009-2011). Carotid and femoral ultrasounds were performed at baseline and after 24 months. A subgroup of 476 patients with CKD was also randomized to undergo ultrasound examination at 12 months. Progression of atheromatosis was defined as an increase in the number of plaque territories analyzed by multivariate logistic regression. RESULTS: Prevalence of atheromatosis was 68.7% and progressed in 59.8% of patients after 24 months. CKD progression was associated with atheromatosis progression, suggesting a close association between pathologies. Variables significantly predicting atheromatosis progression, independent from CKD stages, were diabetes and two interactions of age with ferritin and plaque at baseline. Given that multiple interactions were found between CKD stage and age, phosphate, smoking, dyslipidemia, body mass index, systolic BP (SBP), carotid intima-media thickness, plaque at baseline, uric acid, cholesterol, 25-hydroxy vitamin D (25OH vitamin D), and antiplatelet and phosphate binders use, the analysis was stratified by CKD stages. In stage 3, two interactions (age with phosphate and plaque at baseline) were found, and smoking, diabetes, SBP, low levels of 25OH vitamin D, and no treatment with phosphate binders were positively associated with atheromatosis progression. In stages 4 and 5, three interactions (age with ferritin and plaque and plaque with smoking) were found, and SBP was positively associated with atheromatosis progression. In dialysis, an interaction between body mass index and 25OH vitamin D was found, and age, dyslipidemia, carotid intima-media thickness, low cholesterol, ferritin, and uric acid were positively associated with atheromatosis progression. CONCLUSIONS: Atheromatosis progression affects more than one half of patients with CKD, and predictive factors differ depending on CKD stage. PMID- 26668024 TI - Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND AND OBJECTIVES: People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines. RESULTS: We included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], -20.2 mg/dl; 95% CI, -25.9 to -14.5 mg/dl), LDL-cholesterol (MD, -21.6 mg/dl; 95% CI, -27.9 to -15.4 mg/dl), and calcium (MD, -0.4 mg/dl; 95% CI, -0.6 to -0.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences. CONCLUSIONS: Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis. PMID- 26668025 TI - Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy. AB - BACKGROUND AND OBJECTIVES: Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation. RESULTS: The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology. CONCLUSIONS: APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease. PMID- 26668028 TI - Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death. AB - BACKGROUND AND OBJECTIVES: The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. RESULTS: There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). CONCLUSIONS: Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys. PMID- 26668026 TI - Validating Early Post-Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants. AB - BACKGROUND AND OBJECTIVES: Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post transplant outcome measures is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS. RESULTS: Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92). CONCLUSIONS: OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome. PMID- 26668029 TI - Evolutionary formation of gene clusters by reorganization: the meleagrin/roquefortine paradigm in different fungi. AB - The biosynthesis of secondary metabolites in fungi is catalyzed by enzymes encoded by genes linked in clusters that are frequently co-regulated at the transcriptional level. Formation of gene clusters may take place by de novo assembly of genes recruited from other cellular functions, but also novel gene clusters are formed by reorganization of progenitor clusters and are distributed by horizontal gene transfer. This article reviews (i) the published information on the roquefortine/meleagrin/neoxaline gene clusters of Penicillium chrysogenum (Penicillium rubens) and the short roquefortine cluster of Penicillium roqueforti, and (ii) the correlation of the genes present in those clusters with the enzymes and metabolites derived from these pathways. The P. chrysogenum roq/mel cluster consists of seven genes and includes a gene (roqT) encoding a 12 TMS transporter protein of the MFS family. Interestingly, the orthologous P. roquefortine gene cluster has only four genes and the roqT gene is present as a residual pseudogene that encodes only small peptides. Two of the genes present in the central region of the P. chrysogenum roq/mel cluster have been lost during the evolutionary formation of the short cluster and the order of the structural genes in the cluster has been rearranged. The two lost genes encode a N1 atom hydroxylase (nox) and a roquefortine scaffold-reorganizing oxygenase (sro). As a consequence P. roqueforti has lost the ability to convert the roquefortine-type carbon skeleton to the glandicoline/meleagrin-type scaffold and is unable to produce glandicoline B, meleagrin and neoxaline. The loss of this genetic information is not recent and occurred probably millions of years ago when a progenitor Penicillium strain got adapted to life in a few rich habitats such as cheese, fermented cereal grains or silage. P. roqueforti may be considered as a "domesticated" variant of a progenitor common to contemporary P. chrysogenum and related Penicillia. PMID- 26668027 TI - Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome. AB - BACKGROUND AND OBJECTIVES: Treatment of congenital nephrotic syndrome (CNS) and steroid-resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high-throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50-178). Genotyping was performed systematically in all patients. RESULTS: The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA-induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy. CONCLUSIONS: The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients. PMID- 26668030 TI - Soluble expression and stability enhancement of transcription factors using 30Kc19 cell-penetrating protein. AB - Transcription factors have been studied as an important drug candidate. Ever since the successful generation of induced pluripotent stem cells (iPSCs), there has been tremendous interest in reprogramming transcription factors. Because of the safety risks involved in a virus-based approach, many researchers have been trying to deliver transcription factors using nonintegrating materials. Thus, delivery of transcription factors produced as recombinant proteins in E. coli was proposed as an alternative method. However, the low level of soluble expression and instability of such recombinant proteins are potential barriers. We engineered a Bombyx mori 30Kc19 protein as a fusion partner for transcription factors to overcome those problems. We have previously reported that 30Kc19 protein can be produced as a soluble form in E. coli and has a cell-penetrating property and a protein-stabilizing effect. Transcription factors fused with 30Kc19 (Oct4-30Kc19, Sox2-30Kc19, c-Myc-30Kc19, L-Myc-30Kc19, and Klf4-30Kc19) were produced as recombinant proteins. Interestingly, Oct4 and L-Myc were expressed as a soluble form by conjugating with 30Kc19 protein, whereas Oct4 alone and L-Myc alone aggregated. The 30Kc19 protein also enhanced the stability of transcription factors both in vitro and in cells. In addition, 30Kc19 conjugated transcription factors showed rapid delivery into cells and transcriptional activity significantly increased. Overall, 30Kc19 protein conjugation simultaneously enhanced soluble expression, stability, and transcriptional activity of transcription factors. We propose that the conjugation with 30Kc19 protein is a novel approach to solve the technical bottleneck of gene regulation using transcription factors. PMID- 26668031 TI - Danse Macabre. PMID- 26668033 TI - Authors' reply to Barbieri and Kovarik, Mariani, and Waxman and Kanzaria. PMID- 26668032 TI - Increased Morbidity and Mortality in Domestic Animals Eating Dropped and Bitten Fruit in Bangladeshi Villages: Implications for Zoonotic Disease Transmission. AB - We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02-1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16-1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13-2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption. PMID- 26668036 TI - [A position paper on end of life shared between those who believe and those who don't believe: a dialogue is possible]. AB - In the modern medicine a sound evidence is available today supporting the four fundamental principles representing the best scientific and ethical approach to end of life issues: shared decision making process in a doctor-patient relationship centered care; rejection of dying process marked by the suffering and disproportionate treatments; withholding/withdrawing these treatments and palliative sedation as main contributions to suppress the patients' suffering and pain at the end of life; clear-cut difference between these clinical and ethical options and euthanasia. In some European countries, such as Germany, France, UK, and Spain, these principles are included in a well set legislation regarding the end of life issue, but this is not the case of our country. Despite this failure, in Italy, doctors, patients, and their families, need a law aimed to deal with the complex issues of end of life care as a whole. Therefore, the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI) together with Italian Society of Palliative Care (SICP), shared with the Foundation "Courtyard of the Gentiles" - Department of the Pontifical Council for the Culture - the project to appoint a panel of religious and non-religious experts (physicians, philosophers, legal experts, and politicians) in order to draw up and offer to the political consideration a shared position paper, containing all the ethical and legal principles aimed to outline a more complete regulation of end of life in our country. The "Courtyard of the Gentiles" - whose aim is to promote the dialogue in regard to the issues of contemporary society between those who believe and those who don't believe, with a view to connect political and cultural institutions - appointed the panel in April 2014 and the shared position paper was formally presented on 17 September 2015, in a public conference in the Senate. The physicians who have been part of the panel, affirmed that all the problems related to the legal approach to the decision making process at the end of life may be solved only through a regulation of the doctor-patient relationship centered care. The aim of this regulation will be to set goals, rules, and limits of therapies, patients and doctors rights, procedures able to support and safeguard the good clinical practice, giving to patients and doctors an ethic reference point in the context of a law's guarantee. The fundamental principles of the regulation of the doctor-patient relationship centered care will rest on the contents of code of medical ethics, the safeguard of dignity, autonomy, and health of human beings. In conclusion, we hope to have supplied a useful contribution to draw up in the next future a law able to guarantee the autonomy of doctor-patient relationship, respecting different cultures and religious or non-religious approaches to life and death, as well as the different biography and biology of everyone. Our first goal was to comprehensively address the issue of end of life, understanding the concerns of patients and their families in a very problematic stage of their life, and offering to the doctors a valuable tool for dealing with the increasing complex connection between disease, death and modern medical practice on one hand, and related human fortunes on the other hand. PMID- 26668037 TI - "Commercial stem cells" damage medicine: medicine is aware. AB - A recent Editorial in the NEJM on the flourishing of stem cell clinics providing unproven treatments ona commercial basis and the widespread use of fake cell therapies in the US resonates with worldwide concerns on unproven therapies and in Italy, with the recent and luckily finished "Stamina case". The article brings into focus a resurgence of concern, awareness and willingness to stand up of the broad medical community, in a scenario in which fundamental values of science and medicine are at stake. PMID- 26668038 TI - [Sustainable diet: history lessons]. AB - Global dietary patterns changed dramatically in the past 50 years, presenting both a boom and a threat to the health and well-being of populations everywhere. We need sustainable diets, with low-input, local and seasonal agro-ecological food productions as well as short distance production-consumption nets for fair trade. The development of a global food system able to guarantee everyone a balanced food intake requires health professionals an awareness and a commitment to increasingly complex education. Dietary changes such as the adherence of to the Mediterranean Dietary Pattern can reduce the environmental footprint and thus the use of natural resources. Increased focus on improving the utilization of freshwater fishes and the correct use of the waters of rivers and lakes should also be encouraged. Cultural heritage, food quality and culinary skills are other key aspects determining sustainable dietary patterns and food security. The Mediterranean street food (Mediterraneita), for intrinsic characteristics, can represent valid model to address the main issues concerning the sustainable food system. The issues of sustainability offer a great opportunity to nutritional science and scientists to play a more central role in the political analysis of future food systems. We are confident that preserve the past helps us understand the present and build for the future, the Mediterranean lifestyle is much more than the Mediterranean diet and, finally, the rivers and the lakes may be our future. PMID- 26668039 TI - [Consumption of alcoholic beverages: cultural revolution is necessary]. AB - Significant investment in advertising has been made to promote the consumption of alcoholic beverages, but only 0.5% of the GDP is allocated for preventing alcohol use. Although available evidence clearly demonstrates a causal relationship between ethanol and cancer, the perception of risk in the general population remains extremely low. This is partly due to the fact that alcohol consumption is considered as a "normal" habit in our society, mostly as a consequence of the lack of appropriate information. It should also be emphasized the lack of a common language within the healthcare community, in that too often alcohol is identified as a food or a preservative. The fourth edition of the RDA represents a true cultural revolution as it identifies alcohol consumption as a risk, regardless of the amount consumed. Recommended dosages are defined as low-risk dosages. It would be appropriate to correctly apply the Law 125/2001, which provides for inclusion of alcoholism in university education programs. PMID- 26668040 TI - [Preliminary proposals regarding of an italian law on end-of-life decision making]. AB - In contrast to other European countries (e.g., Germany, France, Spain, the UK), Italy's attempts to regulate end-of-life care have ended in 2009 in a clash of opinion involving lay and religious philosophers, legal experts, and politicians. Rooted in strife and widely criticized from the scientific, moral, and juridical points of view, a bill dealing solely with the issue of advance directives has been lying dormant in the Senate since 2009. The absence of legislation dealing effectively with the complexities of end-of-life care continues to create difficulties in Italian ICUs, for physicians, nurses, patients, and their families. To address this need, the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI) and Italian Society of Palliative Care, (SICP), together with the Department of the Pontifical Council for Culture's Courtyard of the Gentiles Foundation - established in 2009 to promote dialogue between "believers" and "nonbelievers" on issues that impact modern society - have now drafted a shared position paper highlighting the ethical and legal principles, that should inform future attempts to provide Italy with comprehensive laws for regulating end-of-life care in Italy. We report the shared position paper, which was presented in the Italian Senate on 17 September 2015. PMID- 26668041 TI - [The key role of patient in the antipsychotic therapy: shared decision making, adherence and research]. AB - A large number of currently available antipsychotic drugs are included into two main classes: traditional (or first-generation), and atypical (or second generation) antipsychotics. This wide availability of medicinal products allows, at least in part, to address the need to identify the most appropriate treatment for the individual patient. A precondition for the effectiveness of antipsychotic treatment is the adherence, a multi-determined phenomenon that depends on factors related to the pharmacological properties of each agent and on factors independent from the therapy: among them, therapeutic alliance between patients and medical team, patient's belief in benefits and risks of medicines, and patient's relationship with the family and social environment are the most clearly recognized. The collection of data from patient helps the management of the individual clinical case, but this information could also become a source of data for research. In both cases, data must be collected in a ordered and well coded way, therefore numerous instruments (like questionnaires and registers) are developing. This approach permits to make a recognition of patient's perception of his health condition, as well as the positive and negative outcomes of his pharmacological treatment. These tools are known in the literature by the name of PROMs (patient-reported outcome measures). From the clinical point of view, the PROMs can reduce the gap between patient and clinician in different therapeutic areas. They also enables the physician to identify the most suitable treatment to the individual patient, to meet his needs and preferences, and to adapt the therapy over time to the changes of his medical condition. About the research, the effects reported by the patient, in terms of both benefits and adverse reactions, represent important information useful to conduct observational studies that better define the benefit-risk profile of drug therapies, especially in psychiatry. PMID- 26668042 TI - [Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point]. AB - In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohn's disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed. PMID- 26668043 TI - [The early management of the sepsis: use of a guidelines document in hospital. Experience at "Carlo Poma" Hospital in Mantova]. AB - Today the sepsis represents a very important clinical entity. The Surviving Sepsis Campaign assessed an incidence of sepsis equal to 3 cases/1,000 inhabitants. In UK more than 30,000 cases of severe sepsis are calculated; furthermore the patients with sepsis are increasing worldwide (near 18 millions of cases per year). Because of its high mortality, the sepsis represents one of the main causes of death in the world, also in the developing countries where it causes near sixty percent of the total deaths yearly. The early diagnosis and therapy are very important elements for the outcome of the patients. The Authors present the results of the adoption in their hospital of a guidelines document for the management of the septic patient, that show a decrease of their mortality due to the early diagnosis and specific treatments. PMID- 26668044 TI - [Delay in diagnosis of common variable immunodeficiency: a paradigmatic case report]. AB - This case report highlights the frequent delay in diagnosis of common variable immunodeficiency. The patient, 84 years old, had over 30 years of recurrent infections. At the first visit serum IgG were less than 134 mg/dl. From the review of previous examinations strong hypogammaglobulinemia was present for over 14 years. PMID- 26668047 TI - Learning from anomalies: the case of cholesterol and ischaemic heart disease. PMID- 26668048 TI - Intraventricular Extension of Supratentorial Intracerebral Hemorrhage: The Modified Graeb Scale Improves Outcome Prediction in Lund Stroke Register. AB - BACKGROUND/AIMS: The modified Graeb Scale (mGS) is a semi-quantitative method to assess the extension of intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH). The mGS has been shown to prognosticate outcome after ICH in cohorts derived from convenience samples. We evaluated the external validity of mGS in supratentorial ICH-patients from an unselected cohort. METHODS: ICH-patients were included prospectively and consecutively in Lund Stroke Register. Follow-up survival status was obtained from the National Census Office; functional outcome was obtained from the Swedish Stroke Register or medical records. Using multivariate analyses, we examined if mGS was related to 30-day survival or poor functional outcome (modified Rankin Scale >=4) at 90 days. RESULTS: Of 198 supratentorial ICH-patients, 86 (43%) had IVH (median mGS 12, range 1-28). In multivariate regression analyses, the mGS independently predicted 30-day mortality (per point; OR 1.16; 95% CI 1.06-1.27; p = 0.002) and poor functional outcome (OR 1.11; 95% CI 1.02-1.20; p = 0.011) after ICH. In receiver-operator characteristic analysis, the addition of mGS tended to be associated with a higher prognostic accuracy for survival (area under curve 0.886 vs. not including mGS 0.812; p = 0.053). CONCLUSIONS: The mGS improves outcome prediction after supratentorial ICH beyond other previously established factors in an unselected population. PMID- 26668050 TI - A narrative review of undergraduate peer-based healthcare ethics teaching. AB - OBJECTIVE: This study explores the literature in establishing the value of undergraduate peer-based healthcare ethics teaching as an educational methodology. METHODS: A narrative review of the literature concerning peer-based ethics teaching was conducted. MEDLINE, EMBASE, CINAHL, SCOPUS databases, and the Cochrane Library, were systematically searched for studies of peer-based ethics or professionalism teaching. Selected studies related peer-based teaching to ethics education outcomes. RESULTS: Ten publications were identified. Selected studies were varied in their chosen intervention methodology and analysis. Collectively, the identified studies suggest peer-based ethics education is an effective and valued educational methodology in training healthcare professionals. One paper suggests peer-based ethics teaching has advantages over traditional didactic methods. Peer-based ethics teaching also receives positive feedback from student participants. However, the limited literature base demonstrates a clear need for more evaluation of this pedagogy. CONCLUSIONS: The current literature base suggests that undergraduate peer based healthcare ethics teaching is valuable in terms of efficacy and student satisfaction. We conclude that the medical community should invest in further study in order to capitalise upon the potential of peer-based ethics teaching in undergraduate healthcare education. PMID- 26668049 TI - Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media. AB - OBJECTIVE: Validate single versus sequential culture media for murine embryo development. DESIGN: Prospective laboratory experiment. SETTING: Assisted Reproduction Laboratory. ANIMALS: Murine embryos. INTERVENTIONS: Thawed murine zygotes cultured for 3 or 5 days (d3 or d5) in single or sequential embryo culture media developed for human in vitro fertilization. MAIN OUTCOME MEASURES: On d3, zygotes developing to the 8 cell (8C) stage or greater were quantified using 4',6-diamidino-2-phenylindole (DAPI), and quality was assessed by morphological analysis. On d5, the number of embryos reaching the blastocyst stage was counted. DAPI was used to quantify total nuclei and inner cell mass nuclei. Localization of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C terminal hydrolase L3 (UCHL3) was reference points for evaluating cell quality. RESULTS: Comparing outcomes in single versus to sequential media, the odds of embryos developing to the 8C stage on d3 were 2.34 time greater (P = .06). On d5, more embryos reached the blastocyst stage (P = <.0001), hatched, and had significantly more trophoblast cells (P = .005) contributing to the increased total cell number. Also at d5, localization of distinct cytoplasmic UCHL1 and nuclear UCHL3 was found in high-quality hatching blastocysts. Localization of UCHL1 and UCHL3 was diffuse and inappropriately dispersed throughout the cytoplasm in low-quality nonhatching blastocysts. CONCLUSIONS: Single medium yields greater cell numbers, an increased growth rate, and more hatching of murine embryos. Cytoplasmic UCHL1 and nuclear UHCL3 localization patterns were indicative of embryo quality. Our conclusions are limited to murine embryos but one might speculate that single medium may also be more beneficial for human embryo culture. Human embryo studies are needed. PMID- 26668051 TI - Should pregnant women with unknown HIV status be offered rapid HIV testing in labour? PMID- 26668054 TI - Childhood Basal Ganglia Stroke and its Association with Trivial Head Trauma. AB - This study explored the clinical profile, risk factors, neuroimaging and outcome of childhood basal ganglia stroke. Children (6 months-12 years) with basal ganglia stroke registered between 2007-2011 were retrospectively enrolled, while newly diagnosed cases over the 2-year study period were enrolled prospectively. Children with recent trivial head trauma were compared with those without it. Of the 35 children enrolled, trivial head trauma was seen in 74%. The non-trivial head trauma group (n = 9) comprised unidentified etiology (4), Moyamoya syndrome (2), varicella infection (1), homocysteinemia (1), and probable mitochondrial cytopathy (1). Median duration to complete recovery was significantly less in the trivial head trauma group (median = 12, range = 1-72 weeks vs median = 38, range = 20-48 weeks,P= .001). Moreover, these children had increased chances of complete recovery (85% [22/26] vs 44.5% [4/9],P= .029). Basal ganglia stroke can follow trivial head trauma and may have a more favorable outcome. PMID- 26668053 TI - Recording of Neonatal Seizures in Birth Certificates, Maternal Interviews, and Hospital Discharge Abstracts in a Cerebral Palsy Case-Control Study in Michigan. AB - We evaluated the recording of neonatal seizures in birth certificates, hospital discharge abstracts, and maternal interviews in 372 children, 198 of them with cerebral palsy, born in Michigan hospitals from 1993 to 2010. In birth certificates, we examined checkbox items "seizures" or "seizure or serious neurologic dysfunction"; in hospital discharge abstracts ICD-9-CM codes 779.0, 345.X, and 780.3; and in maternal interviews a history of seizures or convulsions on day 1 of life recalled 2-16 years later. In 27 neonates, 38 neonatal seizures were recorded in 1 or more sources, 17 in discharge abstracts, 20 in maternal interviews, but just 1 on a birth certificate. The kappa coefficient (kappa) between interviews and discharge abstracts was moderate (kappa = 0.55), and substantial (kappa = 0.63) if mothers noted use of antiepileptics. Agreement was higher (kappa = 0.71 vs kappa = 0.29) in term births than in preterm births. Birth certificates significantly underreported neonatal seizures. PMID- 26668055 TI - [Management of delirium in the intensive care unit : Non-pharmacological therapy options]. AB - BACKGROUND: Non-pharmacological intervention strategies are used in the prevention and therapy of delirium. OBJECTIVES: Investigation of the effectiveness of non-pharmacological therapy options. METHODS: Analysis of review articles and studies in order to make recommendations for the clinical practice. RESULTS: Reorientation, promotion of mental activities, adequate communication, early physiotherapy and avoidance of both polypharmacy and sleep deprivation have a high impact on the prevention and therapy of delirium. CONCLUSION: Non pharmacological intervention strategies are very important in the prevention and therapy of delirium. PMID- 26668056 TI - Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation. AB - BACKGROUND: Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood. AIM: The developmental stage-specific embryonic induction of tumor cell differentiation was investigated. METHODS: Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4alpha RNA interference was used to verify the role of HNF 4alpha. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice. RESULTS: The 9-11-days chick liver extracts and 13.5-14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4alpha, HNF-1alpha, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4alpha RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4alpha, confirming this embryonic induction effect in vivo. CONCLUSIONS: This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis. PMID- 26668057 TI - Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Hepatoma Management: A Prospective Study. AB - BACKGROUND: For patients with hepatocellular carcinoma (HCC), gadoxetic acid enhanced magnetic resonance imaging (EOB-MRI) improved the diagnosis, migrated Barcelona Clinic Liver Cancer (BCLC) stage, and changed therapeutic decision in retrospective analysis. AIM: This prospective study was to evaluate the clinical impact of EOB-MRI on HCC management. METHODS: From September 2012 to February 2014, consecutive patients with suspicion of HCC in BCLC early stage by multidetector computed tomography or dynamic MRI with non-specific gadolinium, well liver function reserve, and admitted for resection evaluation were enrolled prospectively. Additional EOB-MRI was performed. The HCC diagnosis, BCLC staging, and treatment decision were obtained in a liver cancer conference. EOB-MRI impact on HCC management was analyzed. RESULTS: One hundred and three patients including 68 with typical and 35 with atypical HCC nodules in dynamic imaging studies were enrolled. EOB-MRI characterized 3 (4.4 %) benign and 33 (94.3 %) HCC for patients with typical and atypical HCC nodules, respectively. For 90 HCC patients, additional EOB-MRI changed BCLC stage in 25 (27.8 %) and treatment decision in 17 (18.9 %) patients. There were 66 patients with 78 resected nodules including 65 HCCs, 4 intrahepatic cholangiocarcinomas, and 9 benign nodules. Dynamic study and EOB-MRI detected and characterized 69 and 77 nodules, respectively. The sensitivity and accuracy in HCC diagnosis were 98.5 and 85.7 % for EOB-MRI, which were better than those of dynamic study (p < 0.001). CONCLUSIONS: Additional EOB MRI improved HCC diagnosis in sensitivity, accuracy but not specificity. It changed BCLC staging and treatment decision in 27.8 and 18.9 % of early-stage HCC patients. PMID- 26668059 TI - Hirsutism region and the likelihood of metabolic syndrome: is there a link? PMID- 26668058 TI - Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains. AB - In this study we aimed to provide an in-depth proteomic analysis of differentially expressed proteins in the hearts of transgenic mouse models of pathological and physiological cardiac hypertrophy using tandem mass tag labeling and liquid chromatography tandem mass spectrometry. The Delta43 mouse model, expressing the 43-amino-acid N-terminally truncated myosin essential light chain (ELC) served as a tool to study the mechanisms of physiological cardiac remodeling, while the pathological hypertrophy was investigated in A57G (Alanine 57 -> Glycine) ELC mice. The results showed that 30 proteins were differentially expressed in Delta43 versus A57G hearts as determined by multiple pair comparisons of the mutant versus wild-type (WT) samples with P < 0.05. The A57G hearts showed differential expression of nine mitochondrial proteins involved in metabolic processes compared to four proteins for ?43 hearts when both mutants were compared to WT hearts. Comparisons between ?43 and A57G hearts showed an upregulation of three metabolically important mitochondrial proteins but downregulation of nine proteins in ?43 hearts. The physiological model of cardiac hypertrophy (?43) showed no changes in the levels of Ca(2+)-binding proteins relative to WT, while the pathologic model (A57G) showed the upregulation of three Ca(2+)-binding proteins, including sarcalumenin. Unique differences in chaperone and fatty acid metabolism proteins were also observed in Delta43 versus A57G hearts. The proteomics data support the results from functional studies performed previously on both animal models of cardiac hypertrophy and suggest that the A57G- and not ?43- mediated alterations in fatty acid metabolism and Ca(2+) homeostasis may contribute to pathological cardiac remodeling in A57G hearts. PMID- 26668060 TI - Papillary thyroid carcinomas with biochemical incomplete or indeterminate responses to initial treatment: repeat stimulated thyroglobulin assay to identify disease-free patients. AB - Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg >=1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels <=1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (<10 ng/mL). In unselected PTC cohorts with incomplete/indeterminate biochemical responses to thyroidectomy and RRA, periodic remeasurement of stimulated Tg allows most patients to be classified as disease free. PMID- 26668061 TI - A shared mechanism of muscle wasting in cancer and Huntington's disease. AB - Skeletal muscle loss and dysfunction in aging and chronic diseases is one of the major causes of mortality in patients, and is relevant for a wide variety of diseases such as neurodegeneration and cancer. Muscle loss is accompanied by changes in gene expression and metabolism that lead to contractile impairment and likely affect whole-body metabolism and function. The changes may be caused by inactivity, inflammation, age-related factors or unbalanced nutrition. Although links with skeletal muscle loss have been found in diseases with disparate aetiologies, for example both in Huntington's disease (HD) and cancer cachexia, the outcome is a similar impairment and mortality. This short commentary aims to summarize recent achievements in the identification of common mechanisms leading to the skeletal muscle wasting syndrome seen in diseases as different as cancer and HD. The latter is the most common hereditary neurodegenerative disorder and muscle wasting is an important component of its pathology. In addition, possible therapeutic strategies for anti-cachectic treatment will be also discussed in the light of their translation into possible therapeutic approaches for HD. PMID- 26668062 TI - KRAS mutant lung cancer: progress thus far on an elusive therapeutic target. AB - The KRAS mutation remains the most common driver mutation in patients with non small cell lung cancer (NSCLC) and confers a poor prognosis. Thus far, efforts to target this mutation over the last two decades have been unsuccessful. Over the past 5 years, many efforts to develop drugs that target the RAS-RAF-MEK-ERK (MAPK) pathway have resulted in enhanced understanding of the KRAS mutant NSCLC and have provided optimism that this disease can be targeted. PMID- 26668063 TI - Benchmarks for ethically credible partnerships between industry and academic health centers: beyond disclosure of financial conflicts of interest. AB - Relationships between industry and university-based researchers have been commonplace for decades and have received notable attention concerning the conflicts of interest these relationships may harbor. While new efforts are being made to update conflict of interest policies and make industry relationships with academia more transparent, the development of broader institutional partnerships between industry and academic health centers challenges the efficacy of current policy to effectively manage these innovative partnerships. In this paper, we argue that existing strategies to reduce conflicts of interest are not sufficient to address the emerging models of industry-academic partnerships because they focus too narrowly on financial matters and are not comprehensive enough to mitigate all ethical risk. Moreover, conflict-of-interest strategies are not designed to promote best practices nor the scientific and social benefits of academic-industry collaboration. We propose a framework of principles and benchmarks for "ethically credible partnerships" between industry and academic health centers and describe how this framework may provide a practical and comprehensive approach for designing and evaluating such partnerships. PMID- 26668065 TI - Afatinib, an Irreversible EGFR Family Inhibitor, Shows Activity Toward Pancreatic Cancer Cells, Alone and in Combination with Radiotherapy, Independent of KRAS Status. AB - BACKGROUND: Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients. OBJECTIVE: Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells. METHODS: The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis. RESULTS: Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS (wt)) and Capan-2 (KRAS (mut)) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS (mut)) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization. LIMITATIONS: These results must be confirmed in vivo. CONCLUSIONS: Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status. PMID- 26668064 TI - Pediatric asthma and autism-genomic perspectives. AB - High-throughput technologies, ranging from microarrays to NexGen sequencing of RNA and genomic DNA, have opened new avenues for exploration of the pathobiology of human disease. Comparisons of the architecture of the genome, identification of mutated or modified sequences, and pre-and post- transcriptional regulation of gene expression as disease specific biomarkers are revolutionizing our understanding of the causes of disease and are guiding the development of new therapies. There is enormous heterogeneity in types of genomic variation that occur in human disease. Some are inherited, while others are the result of new somatic or germline mutations or errors in chromosomal replication. In this review, we provide examples of changes that occur in the human genome in two of the most common chronic pediatric disorders, autism and asthma. The incidence and economic burden of both of these disorders are increasing worldwide. Genomic variations have the potential to serve as biomarkers for personalization of therapy and prediction of outcomes. PMID- 26668066 TI - Complete tear of the distal hamstring tendons in a professional football player: a case report and review of the literature. AB - Semimembranosus tendon ruptures are rare and are often associated with involvement of the cruciate ligaments. We present a 24-year-old American football player who sustained a complete rupture of the semimembranosus tendon near its insertion associated with an avulsion fracture of the conjoint attachment of the lateral collateral ligament (LCL) and biceps femoris with intact cruciate ligaments and menisci during practice. At the scene he was immobilized and was taken to the hospital immediately. The diagnosis was reached after radiographs and an MRI of the affected knee were obtained. The semimembranosus tendon and the avulsion of the biceps femoris insertion were repaired surgically. We also review the literature for previously reported cases of distal hamstring injuries. PMID- 26668068 TI - Algal toxin impairs sea lion memory and hippocampal connectivity, with implications for strandings. AB - Domoic acid (DA) is a naturally occurring neurotoxin known to harm marine animals. DA-producing algal blooms are increasing in size and frequency. Although chronic exposure is known to produce brain lesions, the influence of DA toxicosis on behavior in wild animals is unknown. We showed, in a large sample of wild sea lions, that spatial memory deficits are predicted by the extent of right dorsal hippocampal lesions related to natural exposure to DA and that exposure also disrupts hippocampal-thalamic brain networks. Because sea lions are dynamic foragers that rely on flexible navigation, impaired spatial memory may affect survival in the wild. PMID- 26668070 TI - Zombie infections: epidemiology, treatment, and prevention. PMID- 26668069 TI - Semiparametric regression for the weighted composite endpoint of recurrent and terminal events. AB - Recurrent event data are commonly encountered in clinical and epidemiological studies. A major complication arises when recurrent events are terminated by death. To assess the overall effects of covariates on the two types of events, we define a weighted composite endpoint as the cumulative number of recurrent and terminal events properly weighted by the relative severity of each event. We propose a semiparametric proportional rates model which specifies that the (possibly time-varying) covariates have multiplicative effects on the rate function of the weighted composite endpoint while leaving the form of the rate function and the dependence among recurrent and terminal events completely unspecified. We construct appropriate estimators for the regression parameters and the cumulative frequency function. We show that the estimators are consistent and asymptotically normal with variances that can be consistently estimated. We also develop graphical and numerical procedures for checking the adequacy of the model. We then demonstrate the usefulness of the proposed methods in simulation studies. Finally, we provide an application to a major cardiovascular clinical trial. PMID- 26668071 TI - Management recommendations for osteoporosis in clinical guidelines. AB - OBJECTIVE: Numerous guidelines advise about management of osteoporosis, but little research has been conducted on their recommendations. We analysed recommendations on management of bone health in clinical guidelines. DESIGN: We surveyed recommendations on assessment, treatment and monitoring of bone health in 78 clinical guidelines (22 primary focus osteoporosis, 56 primary focus not osteoporosis) lodged at the Agency for Health Research and Quality National Guidelines Clearinghouse between 1/1/2009 and 12/31/2014. MEASUREMENTS: Governance of guidelines; discussion of fracture risk in the target population; recommendations for assessment, treatment and monitoring of bone health. RESULTS: Only 14% of guidelines discussed fracture risk in the target population. When guidelines discussed assessment, 98% recommended bone mineral density (BMD) measurement but only 27% recommended estimation of fracture risk. When guidelines discussed treatment, 63-71% recommended calcium and/or vitamin D, while <12% recommended avoiding low body weight or smoking cessation. When guidelines discussed intervention, 53% did so on the basis of BMD measurement, and only 27% on the basis of estimated fracture risk. When guidelines discussed monitoring, >90% recommended BMD measurements, and only 3% recommended estimation of fracture risk. About 65% of guidelines that suggested a BMD monitoring interval recommended one of <=3 years. Compared to guidelines with a primary focus on osteoporosis, guidelines whose primary focus was not osteoporosis were less likely to discuss fracture risk in the target population (2% vs 45%), recommend estimation of fracture risk (11% vs 55%) and recommend intervention on the basis of estimated fracture risk (10% vs 67%) (all P < 0.005). CONCLUSIONS: Our findings highlight a strong focus in clinical guidelines on BMD, a surrogate measure, rather than fracture risk, the clinically important outcome, particularly when bone health is not the primary focus. Addressing this issue might facilitate more rational use of resources and improve patient care. PMID- 26668072 TI - CrossTalk proposal: Heat acclimatization does improve performance in a cool condition. AB - We believe available data support the thesis that HA can improve performance in cool conditions, and perhaps with less expense and fewer side-effects than hypoxia (Dempsey & Morgan, 2015), but its utility is unresolved and may be modest or absent in some settings and individuals. A few key issues are becoming clear, however. First, HA must be of sufficient stimulus and duration, with key evidence indicating longer is better. Second, individual variability in response to HA as an ergogenic aid needs to be considered. Third, key training aspects such as speed and intensity may need to be maintained, and ideally performed in a cooler environment to maximize gains and minimize fatigue (including the effects of matched absolute versus relative work rates on adaptations). Alternatively, passive heating should be considered (e.g. immediately after training). Fourth, there is no evidence that HA impairs cool weather performance, and thus HA is a useful strategy when the competitive environmental conditions are potentially hot or unknown. Fifth, much remains unknown about ideal timing for competition following HA and its decay. Lastly, an ergogenic effect of HA has yet to be studied in truly elite athletes. PMID- 26668073 TI - Accelerating Oxygen-Reduction Catalysts through Preventing Poisoning with Non Reactive Species by Using Hydrophobic Ionic Liquids. AB - Developing cost-effective electrocatalysts for the oxygen reduction reaction (ORR) is a prerequisite for broad market penetration of low-temperature fuel cells. A major barrier stems from the poisoning of surface sites by nonreactive oxygenated species and the sluggish ORR kinetics on the Pt catalysts. Herein we report a facile approach to accelerating ORR kinetics by using a hydrophobic ionic liquid (IL), which protects Pt sites from surface oxidation, making the IL modified Pt intrinsically more active than its unmodified counterpart. The mass activity of the catalyst is increased by three times to 1.01 A mg(-1) Pt @0.9 V, representing a new record for pure Pt catalysts. The enhanced performance of the IL-modified catalyst can be stabilized after 30 000 cycles. We anticipate these results will form the basis for an unprecedented perspective in the development of high-performing electrocatalysts for fuel-cell applications. PMID- 26668075 TI - Left Ventricular Myocardial Deformation Parameters Are Affected by Coronary Slow Flow Phenomenon: A Study of Speckle Tracking Echocardiography. AB - BACKGROUND: The coronary slow flow phenomenon (CSFP) is defined as a delayed distal vessel contrast opacification in the absence of obstructive epicardial coronary artery disease during coronary angiography. There is conflicting data in medical literature regarding the effects of CSFP on the left ventricular functions assessed by conventional echocardiography or tissue Doppler imaging. Therefore, we aimed to evaluate whether there is any abnormality in the myocardial deformation parameters (strain, strain rate (SR), rotation, twist) of the left ventricle obtained by speckle tracking echocardiography (STE) in patients with CSFP. METHODS: Twenty patients with CSFP were included prospectively in the study. Another 20 patients with similar demographics and cardiovascular risk factors as well as normal coronary angiography were used as the control group. Two-dimensional echocardiographic images of the left ventricle from the apical long-axis, two-chamber, four-chamber, and parasternal short-axis views were used for STE analysis. RESULTS: The analysis of left ventricular circumferential deformation parameters showed that the averaged peak systolic strain, systolic SR, and early diastolic SR values were significantly lower in patients with CSFP (P = 0.009, P = 0.02, and P = 0.02, respectively). Among the left ventricular rotation and twist values, apical rotation was significantly lower in patients with CSFP (P = 0.02). Further, the mean thrombolysis in myocardial infarction frame count value was found to be negatively correlated with the averaged peak circumferential early diastolic SR (r = -0.35, P = 0.03). It was positively correlated with the averaged peak circumferential systolic strain (r = 0.47, P = 0.003) and circumferential systolic SR (r = 0.46, P = 0.005). CONCLUSION: Coronary slow flow phenomenon leads to significant alterations in the myocardial deformation parameters of the left ventricle as assessed by STE. Specifically, circumferential deformation parameters are affected in CSFP patients. PMID- 26668074 TI - Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China. AB - The role of FEN1 genetic variants on gallstone and gallbladder cancer susceptibility is unknown. FEN1 SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method in blood samples from 341 gallbladder cancer patients and 339 healthy controls. The distribution of FEN1-69G > A genotypes among controls (AA, 20.6%; GA, 47.2% and GG 32.2%) was significantly different from that among gallbladder cancer cases (AA, 11.1%; GA, 48.1% and GG, 40.8%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-69G > A GA (OR = 1.73, 95% CI = 1.01 2.63) and the FEN1-69G > A GG (OR = 2.29, 95% CI = 1.31-3.9). The distribution of FEN1 -4150T genotypes among controls (TT, 21.8%;GT, 49.3% and GG 28.9%) was significantly different from that among gallbladder cancer cases (TT, 12.9%; GT, 48.4% and GG 38.7%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-4150T GT(OR = 1.93, 95% CI = 1.04 2.91) and the FEN1-4150T GG(OR = 2.56, 95% CI = 1.37-5.39). A significant trend towards increased association with gallbladder cancer was observed with potentially higher-risk FEN1-69G > A genotypes (P < 0.001, chi2 trend test) and FEN14150G > T (P < 0.001, chi2 trend test) in gallstone presence but not in gallstone absence (P = 0.81, P = 0.89, respectively). In conclusion, this study revealed firstly that FEN1 polymorphisms and haplotypes are associated with gallbladder cancer risk. PMID- 26668076 TI - Ultrasensitive analysis of glucose in serum by capillary electrophoresis with LIF detection in combination with signal amplification strategies and on-column enzymatic assay. AB - A highly specific and sensitive method for glucose quantification in human serum samples based on on-column enzymatic assay is described. In this method, the head of the capillary was used as a nanoliter-microreactor, the diluted samples spiked with a novel fluorogenic reagent named 2-[6-(4'-amino) phenoxy-3H-xanthen-3-on-9 yl] benzoic acid (APF), and the mixed enzyme solutions of glucose oxidase (GOx) and horseradish peroxidase (HRP), were individually injected into the capillary. Hydrogen peroxide (H2 O2 ) generated in situ by catalytic reaction between GOx and glucose, activates APF in the presence of HRP to form a highly fluorescent product, which was electrophoretically separated from the unreacted APF and detected by the LIF detector. The proposed method allowed the determination of glucose down to 10 nM in real samples, with RSD values lower than 3.5%, which also has the potential for measurements of multicomponents in many other systems including measurement of alpha-glucosidase activity and screening for its inhibitors. PMID- 26668077 TI - Isolated new onset 'atypical' optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up. AB - Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab(neg) patients. 37 AQP4-Ab positive (AQP4 Ab(pos)) and 32 AQP4-Ab negative (AQP4-Ab(neg)) patients (8 with MOG-Ab) were identified. The AQP4-Ab(neg) group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab(neg) patients, AQP4-Ab(pos) patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Ab(neg) patients with RION also had poor visual outcome. Up to 35% of AQP4-Ab(neg) patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab(neg) patients (25%) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0-6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab(neg) RION also had a poor visual outcome. Of those without AQP4-Ab, 25% had MOG-Ab and another 25% developed MS; thus, MOG-Ab is associated with AQP4-Ab(neg) non-MS ON. PMID- 26668078 TI - Erratum to: Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS). PMID- 26668079 TI - Valved or valveless ventriculoperitoneal shunting in the treatment of post haemorrhagic hydrocephalus: a population-based consecutive cohort study. AB - BACKGROUND: Implant infection and obstruction are major complications for ventriculoperitoneal shunts in patients with post-haemorrhagic hydrocephalus. In an effort to (1) reduce the incidence of these complications, (2) reduce the rate of shunt failure and (3) shorten the duration of neurosurgical hospitalisation, we have implemented valveless ventriculoperitoneal shunts at our department for adult patients with post-haemorrhagic hydrocephalus and haemorrhagic cerebrospinal fluid at the time of shunt insertion. METHODS: All adult patients (>18 years old) treated for post-haemorrhagic hydrocephalus with ventriculoperitoneal shunting at our institution from 1 January 2008 to 31 December 2014 were included in this retrospective population-based consecutive cohort study. Data were collected by retrospectively reviewing medical records. We compared two different shunt modalities (valveless vs valve-regulated), analysing frequencies of complications, shunt survival and duration of neurosurgical hospitalisation. RESULTS: A total of 214 patients aged 22-86 (mean age, 60.5 +/- 11.5 years) were included, comprising 137 valveless and 77 valve regulated shunts. We found no difference in the rate of surgical shunt revision (p = 0.65) or differences in time interval from insertion to first surgical revision (p = 0.31) between the two shunt modalities. The duration of neurosurgical hospitalisation was shorter for patients receiving a valveless shunt (p = 0.004). Patients with valveless shunts had a lower rate of shunt infection (5.1 % vs 14.3 %, p = 0.02), but a higher rate of overdrainage (10.3 % vs 2.6 %, p = 0.04). CONCLUSION: The use of a valveless shunting for patients with post-haemorrhagic hydrocephalus results in shorter duration of neurosurgical hospitalisation and lower rate of shunt infection, although these advantages should be held up against the risk of overdrainage. We propose valveless shunting to be used as first-line shunting strategy in this patient category, with careful follow-up ensuring that these are substituted by a valve-bearing system if necessary. PMID- 26668080 TI - Intradiploic leptomeningeal cyst in an adult: role of percutaneous contrast injection in dural defect demonstration. AB - Leptomeningeal cysts are commonly seen in children usually following trauma and associated with bulging leptomeninges at the site of fracture. Intradiploic leptomeningeal cyst is an important differential for an expansile lytic lesion in the bony calvarium especially in a patient with a previous history of trauma. Here we present a case of intradiploic leptomeningeal cyst and describe the usefulness of retrograde cisternogram by CT-guided direct percutaneous cyst puncture where a CT cisternogram after intrathecal contrast injection could not demonstrate the dural defect and communication of the subarachnoid space with the intradiploic leptomeningeal cyst. PMID- 26668081 TI - Calibration of the neuromuscular monitor: Is it necessary? PMID- 26668082 TI - In reply: Calibration of the neuromuscular monitor: Is it necessary? PMID- 26668084 TI - Clinical Impact of Abdominal Fat Distribution on Prognosis After Esophagectomy for Esophageal Squamous Cell Carcinoma. AB - BACKGROUND: Excessive visceral fat may promote cancer development and progression because of metabolic derangements. The purpose of this study was to clarify the impact of abdominal fat distribution on patient prognosis after esophagectomy for esophageal squamous cell carcinoma (ESCC). METHODS: Computed tomography volumetry was performed in 150 patients who underwent curative esophagectomy for ESCC between 2012 and 2013. Visceral fat area (VFA) and subcutaneous fat area (SFA) at umbilicus level were measured, and the VFA/SFA ratio was calculated in each patient. Prognoses of the patients were compared between groups classified according to VFA/SFA ratio. RESULTS: Both relapse-free survival and overall survival of the low VFA/SFA group were significantly better than those of the high VFA/SFA group (log-rank test p = 0.005, p = 0.01). Univariate analysis also found that low VFA/SFA ratio significantly predicted an increase in relapse-free and overall survival. In multivariate analysis, low VFA/SFA ratio was an independent factor for relapse-free survival [p = 0.042, hazard ratio (HR) 0.12, 95 % confidence interval (CI) 0.01-0.93]. In addition, low VFA/SFA ratio tended to be a significant variable that predicted better overall survival (p = 0.057, HR 0.14, 95 % CI 0.01-1.05). CONCLUSIONS: Low VFA/SFA ratio was significantly associated with better prognosis in patients who undergo curative esophagectomy for ESCC. Abdominal fat distribution may influence the biological features of ESCC. PMID- 26668083 TI - Predictors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer. AB - BACKGROUND: Some patients with rectal cancer who receive neoadjuvant chemoradiotherapy (nCRT) achieve a pathologic complete response (pCR) and may be eligible for less radical surgery or non-operative management. The aim of this study was to identify variables that predict pCR after nCRT for rectal cancer and to examine the impact of pCR on postoperative complications. METHODS: A retrospective review was performed of the NCDB from 2006 to 2011. Patients with rectal cancer who received nCRT followed by radical resection were included in this study. Multivariable analysis of the association between clinicopathologic characteristics and pCR was performed, and propensity-adjusted analysis was used to identify differences in postoperative morbidity between pCR and non-pCR patients. RESULTS: A total of 23,747 patients were included in the study. Factors associated with pCR included lower tumor grade, lower clinical T and N stage, higher radiation dose, and delaying surgery by more than 6-8 weeks after the end of radiation, while lack of health insurance was linked with a lower likelihood of pCR. Complete response was not associated with an increased risk of major postoperative complications. CONCLUSIONS: Several clinical, pathologic, and treatment variables can help to predict which patients are most likely to have pCR after nCRT for rectal cancer. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options. PMID- 26668085 TI - Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study. AB - BACKGROUND: Sarcopenia is characterized by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was performed to determine the association of sarcopenia with short-term postoperative outcomes after gastrectomy for gastric cancer. METHODS: We conducted a prospective study of 255 consecutive patients with gastric cancer who underwent curative gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. RESULTS: Sarcopenia was present in 32 of 255 patients (12.5 %), and was significantly correlated with advance age, lower body mass index, higher nutritional risk screening (NRS) 2002 score, and lower preoperative serum albumin and hemoglobin. Compared with non-sarcopenic patients, sarcopenic patients had a higher risk of postoperative complications, longer postoperative hospital stay, and more hospital costs. In univariate analysis, sarcopenia (p < 0.001), nutritional risk (NRS 2002 score >=3; p = 0.003), advanced age (>=75 years; p = 0.014), anemia (p = 0.012), hypoalbuminemia (p = 0.029), and diabetes (p = 0.014) were associated with postoperative complications. Multivariable analysis revealed that sarcopenia (p < 0.001) and diabetes (p = 0.006) were independent predictors of postoperative complications. CONCLUSIONS: Sarcopenia is an independent predictor of postoperative complications in patients with gastric cancer after gastrectomy. PMID- 26668086 TI - Stenting as a Bridge to Surgery for Obstructive Colon Cancer: Does It Have Surgical Merit or Oncologic Demerit? AB - PURPOSE: To evaluate the surgical and oncologic outcomes of patients undergoing self-expandable metallic stent (SEMS) placement with elective curative surgery. METHODS: Data from patients admitted with obstructing colon cancer between 2000 and 2012 were analyzed retrospectively. Patients underwent either SEMS placement as a bridge to surgery (stent group, n = 67) or emergency surgery (surgery group, n = 35). Surgical and oncologic outcomes of the groups were compared. RESULTS: Placement of SEMS was technically successful in 98.5% and clinically successful in 89.6% of cases. There were eight (11.9%) stent-related complications, including three migrations (4.5%), four occlusions (6.0%), and one perforation (1.5%). The stent group had a higher laparoscopic resection rate (67.2 vs. 31.4%, p = 0.001) with a lower conversion rate (4.3 vs. 35.3%, p = 0.003). The wound infection rate was significantly higher in the surgery group (37.1 vs. 11.9%, p = 0.003) with no differences in the rate of other complications. The rates of local recurrence and distant metastasis, recurrence-free, and overall survival were not significantly different between the two groups. CONCLUSIONS: Stenting and elective surgery was associated with a higher laparoscopy rate, a lower conversion rate, and a lower wound infection rate compared to emergency surgery but did not affect recurrence or survival. PMID- 26668087 TI - Assessing the influence of historic net and gross land changes on the carbon fluxes of Europe. AB - Legacy effects of land cover/use on carbon fluxes require considering both present and past land cover/use change dynamics. To assess past land use dynamics, model-based reconstructions of historic land cover/use are needed. Most historic reconstructions consider only the net area difference between two time steps (net changes) instead of accounting for all area gains and losses (gross changes). Studies about the impact of gross and net land change accounting methods on the carbon balance are still lacking. In this study, we assessed historic changes in carbon in soils for five land cover/use types and of carbon in above-ground biomass of forests. The assessment focused on Europe for the period 1950 to 2010 with decadal time steps at 1-km spatial resolution using a bookkeeping approach. To assess the implications of gross land change data, we also used net land changes for comparison. Main contributors to carbon sequestration between 1950 and 2010 were afforestation and cropland abandonment leading to 14.6 PgC sequestered carbon (of which 7.6 PgC was in forest biomass). Sequestration was highest for old-growth forest areas. A sequestration dip was reached during the 1970s due to changes in forest management practices. Main contributors to carbon emissions were deforestation (1.7 PgC) and stable cropland areas on peaty soils (0.8 PgC). In total, net fluxes summed up to 203 TgC yr(-1) (98 TgC yr(-1) in forest biomass and 105 TgC yr(-1) in soils). For areas that were subject to land changes in both reconstructions (35% of total area), the differences in carbon fluxes were about 68%. Overall for Europe the difference between accounting for either gross or net land changes led to 7% difference (up to 11% per decade) in carbon fluxes with systematically higher fluxes for gross land change data. PMID- 26668088 TI - Routinely collected electronic health data and STI research: RECORD extension to the STROBE guidelines. PMID- 26668089 TI - Intra-abdominal fluid aspirate from a dog. AB - A 12-year-old, neutered female, Siberian husky, was presented with a 6-months history of progressive abdominal distension, anorexia, and weight loss. The dog appeared normal on physical examination except for marked abdominal distension. A fluid wave was balloted strongly suggesting an abdominal effusion. Ultrasound examination confirmed this clinical finding. Results of the CBC included mild nonregenerative anemia, with an RBC count of 4.9 * 10(6)/uL (reference interval 5.5-8.5 * 10(6)/uL), hemoglobin concentration of 12 g/dL (reference interval 12 18 g/dL), HCT of 36% (reference interval 37-55%), and reticulocytes <60,000/uL. No abnormalities in serum chemistry were detected. PMID- 26668090 TI - Performance of informative priors skeptical of large treatment effects in clinical trials: A simulation study. AB - One of the main advantages of Bayesian analyses of clinical trials is their ability to formally incorporate skepticism about large treatment effects through the use of informative priors. We conducted a simulation study to assess the performance of informative normal, Student- t, and beta distributions in estimating relative risk (RR) or odds ratio (OR) for binary outcomes. Simulation scenarios varied the prior standard deviation (SD; level of skepticism of large treatment effects), outcome rate in the control group, true treatment effect, and sample size. We compared the priors with regards to bias, mean squared error (MSE), and coverage of 95% credible intervals. Simulation results show that the prior SD influenced the posterior to a greater degree than the particular distributional form of the prior. For RR, priors with a 95% interval of 0.50-2.0 performed well in terms of bias, MSE, and coverage under most scenarios. For OR, priors with a wider 95% interval of 0.23-4.35 had good performance. We recommend the use of informative priors that exclude implausibly large treatment effects in analyses of clinical trials, particularly for major outcomes such as mortality. PMID- 26668091 TI - Extending multivariate- t linear mixed models for multiple longitudinal data with censored responses and heavy tails. AB - The analysis of complex longitudinal data is challenging due to several inherent features: (i) more than one series of responses are repeatedly collected on each subject at irregularly occasions over a period of time; (ii) censorship due to limits of quantification of responses arises left- and/or right- censoring effects; (iii) outliers or heavy-tailed noises are possibly embodied within multiple response variables. This article formulates the multivariate- t linear mixed model with censored responses (MtLMMC), which allows the analysts to model such data in the presence of the above described features simultaneously. An efficient expectation conditional maximization either (ECME) algorithm is developed to carry out maximum likelihood estimation of model parameters. The implementation of the E-step relies on the mean and covariance matrix of truncated multivariate- t distributions. To enhance the computational efficiency, two auxiliary permutation matrices are incorporated into the procedure to determine the observed and censored parts of each subject. The proposed methodology is demonstrated via a simulation study and a real application on HIV/AIDS data. PMID- 26668092 TI - [How to do Research? Development and Evaluation of a Research Training for Patients with Mental Disorders]. AB - Objective Participation of mental health services users in research is increasingly acknowledged in Germany. Principles for successful involvement include research training for service users. The aims of the project were (1) to develop and (2) to evaluate a research training. Methods The research training was developed in five participatory meetings and piloted with 28 participants. They answered questions on the research training and about their interest in research, research-related empowerment and research participation. Results Interest in research did not change. But there is a difference between research related empowerment before (t1) and after (t2) the research training (z = - 2.237; p = 0.025). The number of participants registered in scientific studies increased from 4 (t1) to 8 three months later (t3) whereas the number of participants reporting own research ideas decreased from 7 (t1) to 5 (t3). Conclusion Although interest has not been affected, the evaluation shows significant effects on research-related empowerment in participants. Results concerning transfer are divergent. However, feedback was positive. We are planning to disseminate and refine the training. PMID- 26668093 TI - [Please do Something - no Matter what! A Nationwide Online Survey of Mental Health Service Users About the Use of Alternatives to Coercive Measures]. AB - Aim In recent years the legal basis in Germany for the use of coercive measures in psychiatry has changed. Now, coercive measures are permitted only as last resort after milder measures failed. However, there is no regulation of the type or amount of milder measures. In this study, we investigated which and how many milder measures were experienced by service users before coercion was used and which measures they value as potentially helpful to avoid it. Methods A sample of 83 service users was recruited. In an online survey the experience with 21 milder measures and their evaluation as helpful were assessed by self-report. Results On average, participants reported 5.4 experienced milder measures. The most frequent reason provided for why measures failed were structural factors, followed by staff behavior, and reasons caused by the participants themselves. The only milder measure rated by less than 50 % as potentially helpful in avoiding coercive measures was being persuaded to take medication.Conclusion Although many milder measures are perceived as potentially helpful, only few seem to be made use of in routine clinical practice. In order to prevent coercion staff members should apply a wider range of milder measures. PMID- 26668094 TI - [The Portrait of Psychiatry in Novels - Proposal for a Semi-Standardised Compilation]. AB - OBJECTIVE: Psychiatry is portrayed in many novels, yet a (semi-)standardised compilation of this topic is lacking. In this paper we propose such a system. METHODS: With a system that combines quantitative and narrative/hermeneutic research methods, eight novels from four continents and a publication range of over 50 years were analysed. RESULTS: Two matrices allow an overview of the main topics of the novels, especially pertaining to psychiatry (e. g. misuse of power, monetary aspects of psychiatry, stigmatization, psychiatry as a "system", patient therapist relationship, suicides, lobotomy and electroconvulsive therapy), as well as the novels' impact on the public and on the medical community. An unlimited number of novels can be added to these matrices with the long-term goal of constructing a growing database with novels dealing with psychiatry originating from different cultures and eras. CONCLUSION: Novels can be a mirror image of society, and the approach shown in this paper can be used to further insight in the fields of medical history, transcultural psychiatry, and stigma research. PMID- 26668095 TI - Practice pattern of ileal pouch surveillance in academic medical centers in the United States. AB - OBJECTIVE: There is no consensus on whether, when and how to surveil an ileal pouch. The aims of this study were to evaluate experts' opinions and practice patterns on pouch surveillance and to determine if they were associated with detection of neoplasia. METHODS: Eligible physicians were identified by searching the literature in MEDLINE and the physician list of the Crohn's and Colitis Foundation of America and surveying by questionnaire. RESULTS: Fifty-two eligible participants from 32 tertiary institutions were identified. Forty-one physicians (79%) felt that surveillance pouchoscopy was necessary, and 36 (69%) believed that pouchoscopy with biopsy was effective for the detection of neoplasia. Great variation exists with regard to the frequency of surveillance pouchoscopy. Eighteen physicians (35%) reported the detection of a total of 4 pouch dysplasias and 15 pouch cancers within the previous 5 years. The follow-up number of ileal pouches per year was significantly higher in the neoplasia detection group (50 vs 25, P = 0.041). Those who reported detecting neoplasia took even fewer biopsies from the ileal pouch body during the pouchoscopy examination (>3 biopsies per location, 44% vs 82%, P = 0.005). Multivariable analysis showed that the number of patients with ileal pouches followed up per year was the only independent factor associated with the detection of pouch neoplasia (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1-2.1; P = 0.005). CONCLUSION: Most experts agree with performing pouchoscopy and biopsy for surveillance of ileal pouch neoplasia, although the optimal interval varies greatly. The detection of pouch neoplasia appears to be related to patient volume and physician experience. PMID- 26668096 TI - Severe cholestatic hepatitis due to large vessel vasculitis: report of two cases. AB - Giant cell arteritis (GCA) is a vasculitis of medium and large sized vessels that occurs most often in people >50 years of age with associated symptoms of fever, weight loss, headache and jaw claudication. Polymyalgia rheumatica (PMR), which is characterized by aching and stiffness in the shoulders, hip girdle, neck and torso, is intimately associated with GCA, and evidence suggests that GCA and PMR are two phases of the same disease. The occurrence of liver enzyme abnormalities in either of these conditions is rare. Furthermore, as these conditions occur most commonly in the elderly population who may be subject to polypharmacy, patients with elevated aminotransferases due to underlying GCA/PMR may mistakenly have their abnormal liver function tests attributed to drug-induced liver injury. Given the potential complications of these diseases if left untreated, including ischemic stroke and blindness, early recognition and treatment are critical. We report two patients who developed severe cholestatic liver enzyme elevation, which had been initially attributed to drug toxicity, but was ultimately caused by large vessel vasculitis, specifically GCA and PMR. PMID- 26668097 TI - Single cross-sectional area of pectoralis muscle by computed tomography - correlation with bioelectrical impedance based skeletal muscle mass in healthy subjects. AB - PURPOSE: Skeletal muscle depletion is an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD); a recent study demonstrated significant correlations between pectoralis muscle area on an axial CT image and COPD-related traits. The purpose of this study was to evaluate the relation between pectoralis muscle areas on CT scans and total body skeletal muscle mass (SMM) in healthy subjects. METHODS: For 434 subjects that underwent a low-dose chest CT and bioelectrical impedance analysis (BIA) during health screening from January to June of 2014, cross-sectional area of pectoralis muscles were measured in CT scans. Pearson's correlation and multiple linear regression analysis were used to assess the relationship between cross-sectional CT areas of pectoralis muscles and BIA-assessed SMMs. RESULTS: Mean age was 50 +/- 10 years (78.8% were male). The mean cross-sectional area of pectoralis muscles was 24.1 cm2 +/- 6.8. A moderate correlation was observed between pectoralis muscle area and BIA-based SMM (r = 0.665, P<0.001). Multivariable analysis showed CT determined pectoralis muscle area was significantly associated with BIA-assessed SMM after adjusting for gender, weight, height and age (beta = 0.14 +/- 0.02, P<0.001). CONCLUSION: Cross-sectional area of the pectoralis muscles on single axial CT images shows moderate correlation with total body SMM determined by BIA in healthy subjects. PMID- 26668099 TI - Hunter Cancer Research Alliance Annual Symposium 2015. PMID- 26668098 TI - Serum Visfatin Levels in Ulcerative Colitis. AB - BACKGROUND: Previous studies have suggested that adipokines play a role in inflammatory bowel disease by inducing proinflammatory cytokines, but it is uncertain whether visfatin is causally involved in ulcerative colitis (UC). We evaluated visfatin levels in patients who presented with UC flares before and after treatment. METHODS: In this cohort study, we assessed 31 patients with UC in the activation period and remission in the same patients after treatment, and a healthy control group, consisting of 29 persons, at a single academic medical centre between 2010 and 2013. Disease severity was evaluated clinically using Trulove and Witt's criteria. RESULTS: Serum visfatin levels did not vary according to the extent of disease and were significantly higher in patients in the activation period (7.77 +/- 2.41 ng/ml) than in remission (6.18 +/- 2.04 ng/ml) and the healthy controls (6.54 +/- 2.20 ng/ml; P < 0.01 and < 0.05, respectively). In a comparison of patients in the inactive period with the control group, there was no statistically significant difference (P > 0.05). To assess activation of the disease, a visfatin cut-off point for active UC was determined as 6.40, with sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of 72%, 52%, 66.7% (43.0-85.4) and 50.0% (29.1-70.9), respectively. CONCLUSIONS: The visfatin level was higher in the active group than in post-treatment remission and the healthy control group. Sensitivity and specificity were similar to other inflammatory markers for assessing clinical activity, which did not improve clinical outcomes in patients with acute respiratory distress syndrome (ARDS). These findings did not provide a rationale for assessment of UC activation. PMID- 26668102 TI - Embryo Development and Morphology of the Rocky Mountain Wood Tick (Acari: Ixodidae). AB - Dermacentor andersoni Stiles embryogenesis was observed using fluorescent and scanning electron microscopy for eggs held under laboratory conditions (25 degrees C and at 93% relative humidity). Early embryonic cell divisions appeared to be synchronous and holoblastic, giving rise to a uniform blastoderm surrounding the yolk. The cells of the blastoderm became concentrated on one side of the embryo, forming the segmented germ band. Distinct opisthosomal and prosomal segment morphologies, which are characteristic of chelicerate embryos, were observed during germ band elongation. Mouth and leg appendages grew from the prosomal segments. As development progressed, the segments were fused into the idiosoma and capitulum of the free-living larval form. An embryo staging system was established based on embryo developmental morphology and the timing of morphogenetic events. The staging system will serve as a basis for future studies directed at understanding morphogenetic mechanisms or for observing the impact of abiotic factors, such as temperature or humidity, on tick development. PMID- 26668101 TI - Overall Photoelectrochemical Water Splitting using Tandem Cell under Simulated Sunlight. AB - A stand-alone photoelectrochemical (PEC) water-splitting system driven only by sunlight was demonstrated with a tandem-scheme of Pt/CdS/CuGa3 Se5 /(Ag,Cu)GaSe2 photocathode and NiOOH/FeOOH/Mo:BiVO4 photoanode in a neutral phosphate buffer solution as an electrolyte. The as-prepared semi-transparent Mo:BiVO4 layer allows sunlight to pass through the top photoanode and reach the bottom photocathode. Consequently, the tandem cell showed stoichiometric hydrogen and oxygen evolution with a solar-to-hydrogen (STH) conversion efficiency of 0.67 % over 2 h without degradation. The stability and STH efficiency are the highest among similar configuration of PEC tandem cells. PMID- 26668103 TI - OFF! Clip-on Repellent Device With Metofluthrin Tested on Aedes aegypti (Diptera: Culicidae) for Mortality at Different Time Intervals and Distances. AB - The OFF! Clip-on mosquito-repellent device was tested outdoors against Aedes aegypti (L.). A single treatment device was used against batches of caged adult, nonblood fed Ae. aegypti at multiple locations 0.3m from treatment center. Another set of cages was stationed 0.6m from treatment. A final set of cages was placed 0.9m away. Trials ran for durations of 5, 15, 30, and 60 min. Initial knockdown and mortality after 24 h was recorded. The devices had effective knockdown and mortality. This was not sustained at distances greater than 0.3m from the device. PMID- 26668100 TI - Iron deficiency (ID) at both birth and 9 months predicts right frontal EEG asymmetry in infancy. AB - This study considered effects of timing and duration of iron deficiency (ID) on frontal EEG asymmetry in infancy. In healthy term Chinese infants, EEG was recorded at 9 months in three experimental conditions: baseline, peek-a-boo, and stranger approach. Eighty infants provided data for all conditions. Prenatal ID was defined as low cord ferritin or high ZPP/H. Postnatal ID was defined as >= two abnormal iron measures at 9 months. Study groups were pre- and postnatal ID, prenatal ID only, postnatal ID only, and not ID. GLM repeated measure analysis showed a main effect for iron group. The pre- and postnatal ID group had negative asymmetry scores, reflecting right frontal EEG asymmetry (mean +/- SE: -.18 +/- .07) versus prenatal ID only (.00 +/- .04), postnatal ID only (.03 +/- .04), and not ID (.02 +/- .04). Thus, ID at both birth and 9 months was associated with right frontal EEG asymmetry, a neural correlate of behavioral withdrawal and negative emotions. PMID- 26668104 TI - ICU physicians are unable to accurately predict length of stay at admission: a prospective study. AB - OBJECTIVE: To evaluate the accuracy of prediction of intensive care unit length of stay made by physicians at patient admission. DESIGN: Prospective cohort study. SETTING: Three medical-surgical intensive care units in an oncology hospital. PATIENTS: All patients admitted between January and December 2014. INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Intensive care unit (ICU) length of stay was estimated by the physicians responsible for patient admission and categorized as <48 h, 2-5 days or more than 5 days. Agreement between predicted and actual intensive care unit length of stay was calculated. RESULTS: A total of 2955 patients were admitted during the study period. Physicians accurately predicted ICU length of stay in 1557 (52.7%) admissions. ICU length of stay was underestimated in 864 (29.2%) and overestimated in 534 (18.1%) cases. Agreement between predicted and actual intensive care unit length of stay was poor (Kappa = 0.22) and not associated with physician characteristics. Predictions of an intensive care unit length of stay of >5 days were significantly less accurate than those of <48 h and of 2-5 days (31.1, 59.8 and 53.1%, respectively, P < 0.001). CONCLUSIONS: The intensive care unit length of stay prediction in these oncological intensive care units is inaccurate and, ideally, should not be made at admission. PMID- 26668105 TI - Patients' and families' perspectives of patient safety at the end of life: a video-reflexive ethnography study. AB - OBJECTIVE: The aim of this study was to investigate patients' and families' perspectives of safety and quality in the setting of a life-limiting illness. DESIGN: Data reported here were generated from a qualitative study using video reflexive ethnographic methodology. Data were collected over 18 months and generated through participant observation, shadowing of clinicians, field interviews and semi-structured interviews with patients and families. SETTING: The study was conducted at two hospital sites in Sydney, Australia and in patients' homes. PARTICIPANTS: Patients with an advanced life-limiting illness (n = 29) ranging in age between 27 and 89 years and family members (n = 5) participated in the study. RESULTS: Patient safety remains important to dying patients and families. For dying people, iatrogenic harm is not regarded as 'one off' incidents. Rather, harm is experienced as a result of an unfolding series of negative events. Critically, iatrogenic harm is emotional, social and spiritual and not solely technical-clinical misadventure and is inextricably linked with feeling unsafe. Thus, patient safety extends beyond narrowly defined technical clinical parameters to include interpersonal safety. CONCLUSIONS: Current approaches to patient safety do not address fully the needs of dying patients and their families. Patients and their families regard poor communication with and by health professionals to be harmful in and of itself. PMID- 26668106 TI - Quality evaluation of medical care for breast cancer in Japan. AB - OBJECTIVE: The purpose of this study is to measure adherence rate to the quality indicators (QI) in clinical practice to evaluate the quality of care for breast cancer patients in Japan. DESIGN: A retrospective record review. SETTING: Two hundred twenty-four designated breast cancer care hospitals throughout Japan. PARTICIPANTS: A total of 15 227 patients diagnosed with breast cancer in 2005. MAIN OUTCOME MEASURES: The adherence rate of seven items that correspond to QIs of medical care, which were developed using an adaptation of RAND/UCLA (University of California, Los Angeles) appropriateness method. RESULTS: The lowest quality score was the drug therapy adherence to the St. Gallen consensus recommendations, for which the overall quality score 52.8%. The highest quality score was the adherence rate of hormone receptor testing, for which overall quality score was 97.8%. The greatest variations across facilities were for HER-2 testing and for radiation therapy after breast-conserving surgery. The least variation was for hormone receptor testing. CONCLUSIONS: There was a range of measurements for the adherence rate to each QI, suggesting that the desired standards of care had not necessarily pervaded all facilities. It is necessary to strive for widespread implementation of QIs and realization of the significance of measuring the medical care quality among physicians treating breast cancer. PMID- 26668107 TI - Gene coevolution and regulation lock cyclic plant defence peptides to their targets. AB - Plants have evolved many strategies to protect themselves from attack, including peptide toxins that are ribosomally synthesized and thus adaptable directly by genetic polymorphisms. Certain toxins in Clitoria ternatea (butterfly pea) are cyclic cystine-knot peptides of c. 30 residues, called cyclotides, which have co opted the plant's albumin-1 gene family for their production. How butterfly pea albumin-1 genes were commandeered and how these cyclotides are utilized in defence remain unclear. The role of cyclotides in host plant ecology and biotechnological applications requires exploration. We characterized the sequence diversity and expression dynamics of precursor and processing proteins implicated in butterfly pea cyclotide biosynthesis by expression profiling through RNA sequencing (RNA-seq). Peptide-enriched extracts from various organs were tested for activity against insect-like membranes and the model nematode Caenorhabditis elegans. We found that the evolution and deployment of cyclotides involved their diversification to exhibit different chemical properties and expression between organs facing different defensive challenges. Cyclotide-enriched fractions from soil-contacting organs were effective at killing nematodes, whereas similar enriched fractions from aerial organs contained cyclotides that exhibited stronger interactions with insect-like membrane lipids. Cyclotides are employed as versatile and combinatorial mediators of defence in C. ternatea and have specialized to affect different classes of attacking organisms. PMID- 26668108 TI - Analysis of a trial assessing the long-term effectiveness of salicylic acid plasters compared with scalpel debridement in facilitating corn resolution in patients with multiple corns. AB - This study assesses the effect of salicylic acid plasters on the time to resolution of 324 corns experienced by 201 participants taking part in a randomized controlled trial. While the rate of corn resolution was substantively higher in the treatment group than in the control group, treatment was found to be not significantly related to time to corn recurrence when analyzed over the full 12-month follow-up period. Parametric survival analysis modeling of interval censored data and incorporating patient-specific frailty terms was utilized, to model correlation of corns within patients (hazard ratio [HR], 1.189; 95% confidence interval [CI], 0.780-1.813; P = 0.422). Median resolution times were 10.0 months for corns in the treatment group and 13.4 months for corns in the control group. Controlling for treatment, corn type was found to be related to resolution time, with dorsal/interdigital (ID) corns showing better resolution than plantar corns (HR, 1.670; 95% CI, 1.061-2.630; P = 0.027). Median resolution times were 5.9 months for dorsal/ID corns and 14.9 months for plantar corns. Secondary measures relating to quality of life (QoL) and foot-related disability, using the EQ-5D questionnaire and the Manchester Foot Pain and Disability Index (MFPDI), were also assessed at the patient level in multivariate models. Treatment was not significantly related to any of these measures over the whole period of analysis. However, a trend analysis revealed a quadratic trend in QoL and MFPDI scores, arising from a substantive initial improvement between baseline and 3 months, followed by a gradual decrease between 3 and 12 months. PMID- 26668109 TI - Antiferromagnetic Stabilization in the Ti8O12 Cluster. AB - Using the evolutionary algorithm USPEX and DFT+U calculations, we predicted a high-symmetry geometric structure of the bare Ti8 O12 cluster composed of 8 Ti atoms forming a cube, in which O atoms are at midpoints of all of its edges, in excellent agreement with experimental results. Using natural bond orbital analysis, adaptive natural density partitioning algorithm, electron localization function, and partial charge plots, we find the origin of the particular stability of bare Ti8 O12 cluster: unique chemical bonding where eight electrons of Ti atoms interacting with each other in antiferromagnetic fashion to lower the total energy of the system. The bare Ti8 O12 is thus an unusual molecule stabilized by d-orbital antiferromagnetic coupling. PMID- 26668110 TI - Evolving ideas about genetics underlying insect virulence to plant resistance in rice-brown planthopper interactions. AB - Many plant-parasite interactions that include major plant resistance genes have subsequently been shown to exhibit features of gene-for-gene interactions between plant Resistance genes and parasite Avirulence genes. The brown planthopper (BPH) Nilaparvata lugens is an important pest of rice (Oryza sativa). Historically, major Resistance genes have played an important role in agriculture. As is common in gene-for-gene interactions, evolution of BPH virulence compromises the effectiveness of singly-deployed resistance genes. It is therefore surprising that laboratory studies of BPH have supported the conclusion that virulence is conferred by changes in many genes rather than a change in a single gene, as is proposed by the gene-for-gene model. Here we review the behaviour, physiology and genetics of the BPH in the context of host plant resistance. A problem for genetic understanding has been the use of various insect populations that differ in frequencies of virulent genotypes. We show that the previously proposed polygenic inheritance of BPH virulence can be explained by the heterogeneity of parental populations. Genetic mapping of Avirulence genes indicates that virulence is a monogenic trait. These evolving concepts, which have brought the gene-for-gene model back into the picture, are accelerating our understanding of rice-BPH interactions at the molecular level. PMID- 26668112 TI - Sex under the moon. PMID- 26668113 TI - Signaling cascades and the importance of moonlight in coral broadcast mass spawning. AB - Many reef-building corals participate in a mass-spawning event that occurs yearly on the Great Barrier Reef. This coral reproductive event is one of earth's most prominent examples of synchronised behavior, and coral reproductive success is vital to the persistence of coral reef ecosystems. Although several environmental cues have been implicated in the timing of mass spawning, the specific sensory cues that function together with endogenous clock mechanisms to ensure accurate timing of gamete release are largely unknown. Here, we show that moonlight is an important external stimulus for mass spawning synchrony and describe the potential mechanisms underlying the ability of corals to detect environmental triggers for the signaling cascades that ultimately result in gamete release. Our study increases the understanding of reproductive chronobiology in corals and strongly supports the hypothesis that coral gamete release is achieved by a complex array of potential neurohormones and light-sensing molecules. PMID- 26668111 TI - DNA repair and aging: the impact of the p53 family. AB - Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR. PMID- 26668114 TI - Polymicrobial Amniotic Fluid Infection with Mycoplasma/Ureaplasma and Other Bacteria Induces Severe Intra-Amniotic Inflammation Associated with Poor Perinatal Prognosis in Preterm Labor. AB - PROBLEM: To study the relationship between perinatal prognosis in cases of preterm labor (PTL) and polymicrobial infection in amniotic fluid (AF) and intra amniotic (IA) inflammation using a highly sensitive and reliable PCR-based method. METHOD OF STUDY: To detect prokaryotes using a nested PCR-based method, eukaryote-made thermostable DNA polymerase without bacterial DNA contamination was used in combination with bacterial universal primers. We collected AF aseptically from 118 PTL cases and 50 term subjects. RESULTS: The prevalence of microorganisms was 33% (39/118) by PCR and only 7.6% (9/118) by culture. PTL caused by a combination of positive Mycoplasma/Ureaplasma and other bacteria had significantly higher AF IL-8 levels and a significantly shorter amniocentesis-to delivery interval. CONCLUSIONS: Our newly established PCR method is useful for detecting IA microorganisms. Polymicrobial infection with Mycoplasma/Ureaplasma and other bacteria induces severe IA inflammation associated with poor perinatal prognosis in PTL. PMID- 26668115 TI - Rebuttal by Christopher T. Minson and James D. Cotter. PMID- 26668116 TI - Construction of Ultradense Linkage Maps with Lep-MAP2: Stickleback F2 Recombinant Crosses as an Example. AB - High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium, and chromosomal rearrangements across chromosomes, sexes, and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identify errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultradense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (~6 markers/cM) linkage maps containing 18,691 and 20,054 single nucleotide polymorphisms. The two maps showed a high degree of synteny, but female maps were 1.5-2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (<5%) of interchromosomal rearrangements. However, a fairly large (ca. 10 Mb) translocation from autosome to sex chromosome was detected in both maps. These results illustrate the utility and novel features of Lep-MAP2 in assembling high density linkage maps, and their usefulness in revealing evolutionarily interesting properties of genomes, such as strong genome-wide sex bias in recombination rates. PMID- 26668117 TI - Unchanged carbon balance driven by equivalent responses of production and respiration to climate change in a mixed-grass prairie. AB - Responses of grassland carbon (C) cycling to climate change and land use remain a major uncertainty in model prediction of future climate. To explore the impacts of global change on ecosystem C fluxes and the consequent changes in C storage, we have conducted a field experiment with warming (+3 degrees C), altered precipitation (doubled and halved), and annual clipping at the end of growing seasons in a mixed-grass prairie in Oklahoma, USA, from 2009 to 2013. Results showed that although ecosystem respiration (ER) and gross primary production (GPP) negatively responded to warming, net ecosystem exchange of CO2 (NEE) did not significantly change under warming. Doubled precipitation stimulated and halved precipitation suppressed ER and GPP equivalently, with the net outcome being unchanged in NEE. These results indicate that warming and altered precipitation do not necessarily have profound impacts on ecosystem C storage. In addition, we found that clipping enhanced NEE due to a stronger positive response of GPP compared to ER, indicating that clipping could potentially be an effective land practice that could increase C storage. No significant interactions between warming, altered precipitation, and clipping were observed. Meanwhile, we found that belowground net primary production (BNPP) in general was sensitive to climate change and land use though no significant changes were found in NPP across treatments. Moreover, negative correlations of the ER/GPP ratio with soil temperature and moisture did not differ across treatments, highlighting the roles of abiotic factors in mediating ecosystem C fluxes in this grassland. Importantly, our results suggest that belowground C cycling (e.g., BNPP) could respond to climate change with no alterations in ecosystem C storage in the same period. PMID- 26668120 TI - Thyroid cancer in 2015: Molecular landscape of thyroid cancer continues to be deciphered. PMID- 26668118 TI - Nongenomic actions of thyroid hormone. AB - The nongenomic actions of thyroid hormone begin at receptors in the plasma membrane, mitochondria or cytoplasm. These receptors can share structural homologies with nuclear thyroid hormone receptors (TRs) that mediate transcriptional actions of T3, or have no homologies with TR, such as the plasma membrane receptor on integrin alphavbeta3. Nongenomic actions initiated at the plasma membrane by T4 via integrin alphavbeta3 can induce gene expression that affects angiogenesis and cell proliferation, therefore, both nongenomic and genomic effects can overlap in the nucleus. In the cytoplasm, a truncated TRalpha isoform mediates T4-dependent regulation of intracellular microfilament organization, contributing to cell and tissue structure. p30 TRalpha1 is another shortened TR isoform found at the plasma membrane that binds T3 and mediates nongenomic hormonal effects in bone cells. T3 and 3,5-diiodo-L-thyronine are important to the complex nongenomic regulation of cellular respiration in mitochondria. Thus, nongenomic actions expand the repertoire of cellular events controlled by thyroid hormone and can modulate TR-dependent nuclear events. Here, we review the experimental approaches required to define nongenomic actions of the hormone, enumerate the known nongenomic effects of the hormone and their molecular basis, and discuss the possible physiological or pathophysiological consequences of these actions. PMID- 26668119 TI - The diabetogenic action of statins - mechanisms and clinical implications. AB - Treatment with statins has transformed primary and secondary prevention of cardiovascular disease (CVD), including thrombotic stroke. Evidence-based data demonstrate the benefits and safety of statin therapy and help to guide clinicians in the management of populations at high risk of CVD. Nevertheless, clinical trials, meta-analyses and observational studies highlight a 10-12% increase in new-onset diabetes mellitus (NODM) among patients receiving statins. The risk further increases with intensive therapy and among individuals with known risk factors for NODM. Mechanisms underpinning this effect are not yet fully understood; however, Mendelian randomization studies suggest that they are related to lowered activity of HMG-CoA reductase, the target of statin therapy. In vitro research indicates that statins potentially impair beta-cell function and decrease insulin sensitivity but how these findings relate to patients is unknown. In the clinic, statins should be prescribed on the basis of CVD risk and individual patient characteristics. In addition, diet and lifestyle interventions should be emphasized to help mitigate the risk of NODM. Individuals who develop NODM while taking statins do not exhibit increased microvascular disease, which is reassuring. In diabetes mellitus of long duration, the effect of statins on glycaemic control is small and unlikely to be clinically important. PMID- 26668121 TI - Thyroid: No fasting required for liquid levothyroxine. PMID- 26668122 TI - Gut microbiota: Antidiabetic drug treatment confounds gut dysbiosis associated with type 2 diabetes mellitus. PMID- 26668123 TI - Polyphenolic Secondary Metabolites Synergize the Activity of Commercial Antibiotics against Clinical Isolates of beta-Lactamase-producing Klebsiella pneumoniae. AB - Emergence of worldwide antimicrobial resistance prompted us to study the resistance modifying potential of plant-derived dietary polyphenols, mainly caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin. These compounds were studied in logical combination with clinically significant antibiotics (ciprofloxacin/gentamicin/tetracycline) against Klebsiella pneumoniae, after conducting phenotypic screening of a large number of clinical isolates and selecting the relevant strains possessing extended-spectrum beta lactamase (ESBL) and K. pneumoniae carbapenemase (KPC)-type carbapenemase enzymes only. The study demonstrated that EGCG and caffeic acid could synergize the activity of tested antibiotics within a major population of beta-lactamase producing K. pneumoniae. In spectrofluorimetric assay, ~17-fold greater ciprofloxacin accumulation was observed within K. pneumoniae cells pre-treated with EGCG in comparison with the untreated control, indicating its ability to synergize ciprofloxacin to restrain active drug-efflux. Further, electron micrograph of ESBL-producing K. pneumoniae clearly demonstrated the prospective efficacy of EGCG towards biofilm degradation. PMID- 26668124 TI - A new algorithm for construction of coarse-grained sites of large biomolecules. AB - The development of coarse-grained (CG) models for large biomolecules remains a challenge in multiscale simulations, including a rigorous definition of CG representations for them. In this work, we proposed a new stepwise optimization imposed with the boundary-constraint (SOBC) algorithm to construct the CG sites of large biomolecules, based on the s cheme of essential dynamics CG. By means of SOBC, we can rigorously derive the CG representations of biomolecules with less computational cost. The SOBC is particularly efficient for the CG definition of large systems with thousands of residues. The resulted CG sites can be parameterized as a CG model using the normal mode analysis based fluctuation matching method. Through normal mode analysis, the obtained modes of CG model can accurately reflect the functionally related slow motions of biomolecules. The SOBC algorithm can be used for the construction of CG sites of large biomolecules such as F-actin and for the study of mechanical properties of biomaterials. PMID- 26668125 TI - Serum protein profiles of patients with lung cancer of different histological types. AB - AIMS: To compare serum protein expression profiles between lung cancer patients and healthy individuals, and to examine whether there are differences in serum protein expression profiles among patients with lung cancers of different histological types and whether the characteristic expression of serum proteins may assist in differential diagnosis of various subtypes of lung cancers. METHODS: Blood samples were collected from 123 lung cancer patients before commencement of treatment who attended Shanxi Cancer Hospital, China, between 2008 and 2013. Blood samples from 60 healthy individuals were also collected in the same period. Serum protein expression profiles were analyzed using surface enhanced laser desorption/ionization time-of-flight mass spectrometry. The differences in the serum protein spectrums of lung cancer patients with different histological subtypes were analyzed by one-way Analysis of Variance and receiver operating characteristic curves. RESULTS: A cluster of 48 protein mass-to-change ratio (M/Z) peaks was differentially expressed between sera of lung cancer patients and healthy individuals. The M/Z 1205, 4673, 1429 and 4279 peaks were differentially expressed among patients with lung squamous cell carcinomas, adenocarcinomas and small-cell lung carcinomas. CONCLUSION: These results reinforce the notion that profiling of serum proteins may be of diagnostic value in lung cancer, and suggest that the differences in serum protein profiles may be useful in differential diagnosis of lung cancers of varying histological subtypes. PMID- 26668127 TI - Protoporphyrin IX-Functionalized AgSiO2 Core-Shell Nanoparticles: Plasmonic Enhancement of Fluorescence and Singlet Oxygen Production. AB - Metal-enhanced processes arising from the coupling of a dye with metallic nanoparticles (NPs) have been widely reported. However, few studies have simultaneously investigated these mechanisms from the viewpoint of dye fluorescence and photoactivity. Herein, protoporphyrin IX (PpIX) is grafted onto the surface of silver core silica shell NPs in order to investigate the effect of silver (Ag) localized surface plasmon resonance (LSPR) on PpIX fluorescence and PpIX singlet oxygen (1 O2 ) production. Using two Ag core sizes, we report a systematic study of these photophysical processes as a function of silica (SiO2 ) spacer thickness, LSPR band position and excitation wavelength. The excitation of Ag NP LSPR, which overlaps the PpIX absorption band, leads to the concomitant enhancement of PpIX fluorescence and 1 O2 production independently of the Ag core size, but in a more pronounced way for larger Ag cores. These enhancements result from the increase in the PpIX excitation rate through the LSPR excitation and decrease when the distance between PpIX and Ag NPs increases. A maximum fluorescence enhancement of up to 14-fold, together with an increase in photogenerated 1 O2 production of up to five times are obtained using 100 nm Ag cores coated with a 5 nm thick silica coating. PMID- 26668126 TI - Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5). PMID- 26668128 TI - EndoAnchors to Resolve Persistent Type Ia Endoleak Secondary to Proximal Cuff With Parallel Graft Placement. AB - PURPOSE: To describe 2 patients with a distally migrated endograft causing a type Ia endoleak and treatment with a proximal cuff and chimney grafts that required EndoAnchors to finally seal the leak. CASE REPORT: Two men, ages 86 and 72 years, presented with stent-graft migration and type Ia endoleak at 5 and 15 years after endovascular repair, respectively. Both were treated with a proximal cuff in combination with a chimney graft to the left renal artery. In both cases, the type Ia endoleak persisted, likely due to gutter formation. Both patients were treated in the same setting with EndoAnchors that instantly resolved the endoleak. At 1-year follow-up, there was no recurrent endoleak or migration, with patent chimney grafts and renal arteries and stable renal function. CONCLUSION: EndoAnchors may effectively resolve a persistent type Ia endoleak arising from gutter formation after placement of a proximal cuff and chimney grafts. PMID- 26668129 TI - New Advances in Endovascular Therapy: Endovascular Repair of a Chronic DeBakey Type II Aortic Dissection With a Scalloped Stent-Graft Designed for the Ascending Aorta. AB - PURPOSE: To describe the deployment into the ascending aorta of a fenestrated stent-graft with a scallop for the innominate artery. TECHNIQUE: A 72-year-old multimorbid patient presented with a chronic DeBakey type II aortic dissection of the ventral ascending aorta with close proximity (16 mm) to the innominate artery. A 1-piece, 46-mm-diameter Zenith Ascend Thoracic Endovascular Graft with circumferential diameter-reducing sutures (ProForm) was custom made with a 15*30 mm scallop for the innominate artery. The stent-graft was loaded on a Z-Trak Plus Introducer System with a 20-F hydrophilic-coated sheath and successfully implanted under inflow occlusion in a procedure that lasted 35 minutes. CONCLUSION: The use of fenestrated stent-grafts in the ascending aorta is feasible, and a scallop in the distal stent-graft can extend coverage of the ascending aorta in pathologies close to the innominate artery. This technique broadens the range of endovascular options for patients not suitable for open surgery. PMID- 26668130 TI - Two-Dimensional Perfusion Angiography of the Foot: Technical Considerations and Initial Analysis. AB - PURPOSE: To report the feasibility, technical considerations, and initial results of 2-dimensional (2D) perfusion angiography of the foot before and after endovascular interventions. METHODS: A retrospective single-center study involved 21 patients (mean age 73.4+/-10.5 years; 14 men) with severe peripheral vascular disease [Fontaine stage III (n=10) or IV (n=14)] who underwent lower limb digital subtraction angiography (DSA) prior to and following endovascular treatment of above- and/or below-knee lesions. A standardized contrast administration protocol (15 mL iodixanol 320 mg I/mL at 3 mL/s via a 5/6-F antegrade sheath) was applied during DSA using a 2D perfusion-enabled image intensifier. Representative hindfoot and forefoot regions of interest were analyzed, and representative numeric density values [time to peak (TTP), peak density value (PDV), and area under the (time-density) curve (AUC)] were calculated using 2D perfusion-enabled angiographic software to assess foot perfusion. Values were compared before and after angioplasty and by level of treatment (above or below knee). The parameters were correlated with disease severity (stenosis vs occlusion) and symptom level (Fontaine stage). RESULTS: A clinically significant improvement (29.4%) in the AUC was noted following angioplasty, reaching statistical significance within the hindfoot (p=0.03). No significant change in TTP or PDV was detected following angioplasty. Foot movement remained problematic when measuring time-density values. No statistical difference in perfusion values was appreciable between above- and below-knee angioplasty. CONCLUSION: Two-dimensional perfusion angiography of the foot allows quantitative evaluation using various density values with potential benefit for treatment planning and technical outcome analysis. Methodical restrictions currently remain, mainly regarding patient movement. PMID- 26668131 TI - Disruption of Golgi morphology and altered protein glycosylation in PLA2G6 associated neurodegeneration. AB - BACKGROUND: Mutations in PLA2G6, which encodes the calcium-independent phospholipase A2 group VI, cause neurodegeneration and diffuse cortical Lewy body formation by a yet undefined mechanism. We assessed whether altered protein glycosylation due to abnormal Golgi morphology might be a factor in the pathology of this disease. METHODS: Three patients presented with PLA2G6-associated neurodegeneration (PLAN); two had infantile neuroaxonal dystrophy (INAD) and one had adult-onset dystonia-parkinsonism. We analysed protein N-linked and O-linked glycosylation in cerebrospinal fluid, plasma, urine, and cultured skin fibroblasts using high performance liquid chromatography (HPLC) and matrix assisted laser desorption ionization--time of flight/mass spectrometry (MALDI TOF/MS). We also assessed sialylation and Golgi morphology in cultured fibroblasts by immunofluorescence and performed rescue experiments using a lentiviral vector. RESULTS: The patients with INAD had PLA2G6 mutations NM_003560.2: c.[950G>T];[426-1077dup] and c.[1799G>A];[2221C>T] and the patient with dystonia-parkinsonism had PLA2G6 mutations NM_003560.2: c.[609G>A];[2222G>A]. All three patients had altered Golgi morphology and abnormalities of protein O-linked glycosylation and sialylation in cultured fibroblasts that were rescued by lentiviral overexpression of wild type PLA2G6. CONCLUSIONS: Our findings add altered Golgi morphology, O-linked glycosylation and sialylation defects to the phenotypical spectrum of PLAN; these pathways are essential for correct processing and distribution of proteins. Lewy body and Tau pathology, two neuropathological features of PLAN, could emerge from these defects. Therefore, Golgi morphology, O-linked glycosylation and sialylation may play a role in the pathogenesis of PLAN and perhaps other neurodegenerative disorders. PMID- 26668132 TI - The immunogenicity of platelet-derived FVIII in hemophilia A mice with or without preexisting anti-FVIII immunity. AB - Evidence shows that factor VIII (FVIII) ectopically expressed in platelets (2bF8) is therapeutic in FVIII(null) mice even with anti-FVIII inhibitory antibodies (inhibitors). If current efforts to generate platelets in vitro succeed, genetically manipulated platelets containing FVIII may be used therapeutically in hemophilia A patients with inhibitors. One important concern is the immunogenicity of platelet-derived FVIII. To address this concern, we infused 2bF8 transgenic (2bF8(Tg)) platelets into naive FVIII(null) mice weekly for 8 weeks. No anti-FVIII antibodies were detected in the infused animals during the study course. We then explored whether platelet-derived FVIII is immunogenic in FVIII(null) mice with inhibitors. The 2bF8(Tg) platelets were transfused into rhF8-primed FVIII(null) mice, resulting in no augmentation of anti-FVIII antibodies. To investigate whether preconditioning affects the immune response, animals were sublethally irradiated and subsequently transfused with 2bF8(Tg) platelets. No anti-FVIII antibodies were detected in the recipients after platelet infusions. Following further challenge with rhF8, the inhibitor titer in this group was significantly lower than in naive FVIII(null) mice utilizing the same immunization protocol. Thus, our data demonstrate that infusion of platelets containing FVIII triggers neither primary nor memory anti-FVIII immune response in FVIII(null) mice and that sublethal irradiation plus 2bF8(Tg) platelet infusion suppresses anti-FVIII immune response in FVIII(null) mice. PMID- 26668133 TI - Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. AB - Mutations in the calreticulin gene (CALR) represented by deletions and insertions in exon 9 inducing a -1/+2 frameshift are associated with a significant fraction of myeloproliferative neoplasms (MPNs). The mechanisms by which CALR mutants induce MPN are unknown. Here, we show by transcriptional, proliferation, biochemical, and primary cell assays that the pathogenic CALR mutants specifically activate the thrombopoietin receptor (TpoR/MPL). No activation is detected with a battery of type I and II cytokine receptors, except granulocyte colony-stimulating factor receptor, which supported only transient and weak activation. CALR mutants induce ligand-independent activation of JAK2/STAT/phosphatydylinositol-3'-kinase (PI3-K) and mitogen-activated protein (MAP) kinase pathways via TpoR, and autonomous growth in Ba/F3 cells. In these transformed cells, no synergy is observed between JAK2 and PI3-K inhibitors in inhibiting cytokine-independent proliferation, thus showing a major difference from JAK2V617F cells where such synergy is strong. TpoR activation was dependent on its extracellular domain and its N-glycosylation, especially at N117. The glycan binding site and the novel C-terminal tail of the mutant CALR proteins were required for TpoR activation. A soluble form of TpoR was able to prevent activation of full-length TpoR provided that it was N-glycosylated. By confocal microscopy and subcellular fractionation, CALR mutants exhibit different intracellular localization from that of wild-type CALR. Finally, knocking down either MPL/TpoR or JAK2 in megakaryocytic progenitors from patients carrying CALR mutations inhibited cytokine-independent megakaryocytic colony formation. Taken together, our study provides a novel signaling paradigm, whereby a mutated chaperone constitutively activates cytokine receptor signaling. PMID- 26668135 TI - How many species of whipworms do we share? Whipworms from man and other primates form two phylogenetic lineages. PMID- 26668134 TI - Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis. AB - There is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor gammadelta, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High risk SMM patients showed at baseline decreased expression of activation (CD25/CD28/CD54), type 1 T helper-(CD195/interferon-gamma/tumor necrosis factor alpha/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma. The QUIREDEX trial was registered to www.clinicaltrials.gov as #NCT00480363. PMID- 26668136 TI - Is there a role for e-cigarettes in smoking cessation? AB - The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. PMID- 26668138 TI - Epidemiological Status of Chronic Diabetic Complications in China. PMID- 26668137 TI - The combination of fluticasone furoate and vilanterol trifenatate in the management of asthma: clinical trial evidence and experience. AB - The treatment of persistent asthma has been aided by the recent approval of new medications. The combined inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) powder inhaler fluticasone furoate (FF)/vilanterol trifenatate (VI) is one of these new agents, which was recently approved as a maintenance therapy for persistent asthma. This once-daily ICS/LABA inhaler has previously been approved and used in chronic obstructive pulmonary disease as a maintenance therapy. Both FF and VI individually have been shown to have efficacy in the treatment of persistent asthma; the combination of FF/VI at the dose of 100/25 MUg daily improves trough peak expiratory flows and forced expiratory volume in 1 s. It also reduces the frequency of asthma exacerbations in patients with persistent asthma. The once-daily dosing is well tolerated, with limited clinically significant adverse events; the once-daily inhaled dosing regimen should also improve medication adherence. The data supporting the use of the FF/VI inhaler in persistent asthma are reviewed. The dry powder inhaler of FF/VI (100/25 MUg) is an effective and well tolerated once-daily maintenance treatment for patients with persistent asthma. PMID- 26668139 TI - Performance of Fasting Plasma Glucose and Postprandial Urine Glucose in Screening for Diabetes in Chinese High-risk Population. AB - BACKGROUND: The conventional approaches to diabetes screening are potentially limited by poor compliance and laboratory demand. This study aimed to evaluate the performance of fasting plasma glucose (FPG) and postprandial urine glucose (PUG) in screening for diabetes in Chinese high-risk population. METHODS: Nine hundred and nine subjects with high-risk factors of diabetes underwent oral glucose tolerance test after an overnight fast. FPG, hemoglobin A1c, 2-h plasma glucose (2 h-PG), and 2 h-PUG were evaluated. Diabetes and prediabetes were defined by the American Diabetes Association criteria. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of 2 h-PUG, and the optimal cut-off determined to provide the largest Youden index. Spearman correlation was used for relationship analysis. RESULTS: Among 909 subjects, 33.4% (304/909) of subjects had prediabetes, and 17.2% (156/909) had diabetes. The 2 h-PUG was positively related to FPG and 2 h-PG (r = 0.428 and 0.551, respectively, both P < 0.001). For estimation of 2 h-PG >= 7.8 mmol/L and 2 h-PG >= 11.1 mmol/L using 2 h-PUG, the area under the ROC curve were 0.772 (95% confidence interval [CI ]: 0.738-0.806) and 0.885 (95% CI: 0.850 0.921), respectively. The corresponding optimal cut-offs for 2 h-PUG were 5.6 mmol/L and 7.5 mmol/L, respectively. Compared with FPG alone, FPG combined with 2 h-PUG had a higher sensitivity for detecting glucose abnormalities (84.1% vs. 73.7%, P < 0.001) and diabetes (82.7% vs. 48.1%, P < 0.001). CONCLUSION: FPG combined with 2 h-PUG substantially improves the sensitivity in detecting prediabetes and diabetes relative to FPG alone, and may represent an efficient layperson-oriented diabetes screening method. PMID- 26668140 TI - Relationship Between Serum Zinc Level and Microvascular Complications in Patients with Type 2 Diabetes. AB - BACKGROUND: Previous studies suggested that zinc level was related to a certain diabetic microvascular complication. However, the relationship between zinc level and all the microvascular complications in type 2 diabetic patients remains unknown. The purpose of this study was to analyze the relationship between zinc level and each diabetic microvascular complication and identify the features related to low serum zinc level. METHODS: We included the hospitalized patients with type 2 diabetes (T2D) at our department from May 30, 2013 to March 31, 2014. We initially compared the serum zinc levels between patients with specific microvascular complications and those without. We then analyzed the association between zinc level and each microvascular complication. Furthermore, we identified the unique features of patients with high and low serum zinc levels and analyzed the risk factors related to low zinc level. RESULTS: The 412 patients included 271 with microvascular complications and 141 without any microvascular complications. Serum zinc level was significantly lower in patients with diabetic retinopathy (P < 0.001), diabetic nephropathy (DN, P < 0.001), or diabetic peripheral neuropathy (P = 0.002) compared with patients without that specific complication. Lower zinc level was an independent risk factor for DN (odds ratio = 0.869, 95% confidence interval = 0.765-0.987, P < 0.05). The subjects with lower serum zinc level had manifested a longer duration of diabetes, higher level of hemoglobin A1c, higher prevalence of hypertension and microvascular complications, and lower fasting and 2-h C-peptide levels. CONCLUSIONS: Lower serum zinc level in T2D patients was related to higher prevalence of diabetic microvascular complications, and represented as an independent risk factor for DN. Patients with lower zinc level were more likely to have a longer duration of diabetes, poorer glucose control, and worse beta cell function. PMID- 26668141 TI - Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study. AB - BACKGROUND: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. METHODS: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. RESULTS: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (beta = 0.364, P = 0.001) and maximum pressure (beta = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (beta = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (beta = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (beta = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (beta = 0.244, P = 0.014), and calluses over the course of the study. CONCLUSIONS: We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses. PMID- 26668142 TI - Effects of Sleep Disorders on Hemoglobin A1c Levels in Type 2 Diabetic Patients. AB - BACKGROUND: Studies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels). METHODS: We used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels. RESULTS: The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders. CONCLUSIONS: Sleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control. PMID- 26668143 TI - A Population-based Study of Invasive Cervical Cancer Patients in Beijing: 1993 2008. AB - BACKGROUND: In recent years, the incidence of cervical cancer has been rising, particularly in young adults, as the second most common gynecological cancer in China. The aim of this study was to explore the incidence change and the epidemiological characteristics of cervical cancer in Beijing over the past 16 years. METHODS: All the cases of the study were limited to Beijing residents diagnosed with cervical cancer and registered in Beijing from January 1, 1993, to December 31, 2008. A total of 4100 patients with cervical cancer were obtained from the Statistics Database of Beijing Cancer Registry (BJCaR). According to the registered data, we retrospectively reviewed all original cases which we can acquired in reported hospital. Cervical situ cancer, cervical metastatic cancer, non-Beijing residents and repeatedly registered cases were excluded. Totally, 3641 registered cases were verified correctly. Meanwhile, we also collected the following data: Age, occupation, detected methods, histological type, and staging. The trends of incidence and mortality were analyzed by Joinpoint Regression Program 4.1.1.1 produced by National Cancer Institute (NCI, USA). The annual percent change (APC) was calculated using the Joinpoint regression model. RESULTS: The crude rates of incidence and mortality were 10.4 and 1.0 per 100,000 women, respectively during 1993 to 2008. The average WHO age-standardized incidence rates were 11.5 per 100,000 women. There was a decrease in incidence annually by 8.0% (P = 0.3) during 1993-1996 and a rapid increase annually by 18.9% after 1999 (P < 0.01). The median age was 67 years in 1993, but the median age decreased to 45 years in 2008. The peak of the age-specific incidence curve was at 40 years in the most recent period (2005-2008), which was 25-30 years earlier than that in previous periods (1993-1996). In the 2224 cases, the numbers of patients with stage I, II, III and IV were 910 (40.9%), 601 (27%), 542 (24.4%), 171 (7.7%), respectively. The percentage of patients with stage I was 7.6% (13/171) in 1993-1996, but the percentage increased to 51.6% (643/1247) in 2005-2008 (P < 0.01). Otherwise the percentage of advanced stage (stage III-IV) during the same period was dropped down significantly from 52.0% (89/171) to 22.5% (280/1247) (P < 0.01). Unemployed and housewife ranked first accounting for 27.3% of the total (607/2224). Urban low-income people such as worker ranked the second accounting for 17.0% (377/2224), the third place was farmer accounting for 14.0% (312/2224). Only 381 (17.1%, 381/2224) women in 2224 were first detected cervical cancer by routine screenings. Company staff (36.5%, 139/381), professional and technical personnel (22.6%, 86/381), national official (22.0%, 84/381) occupied the top three (total 81.1%) in the 381 patients detected cervical cancer by screening. CONCLUSIONS: The cervical cancer incidence has showed a continuous rise in Beijing since 1999. Government-led mass screening should target the low socioeconomic population primarily. Meanwhile the government should enhance public health education of cancer screening to increase the rate of screening. PMID- 26668144 TI - Single-nucleotide Polymorphism rs2275294 in ZNF512B is not Associated with Susceptibility to Amyotrophic Lateral Sclerosis in a Large Chinese Cohort. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort. METHODS: To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing. RESULTS: The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15). CONCLUSIONS: The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future. PMID- 26668145 TI - Randomized Trial of Immediate Postoperative Pain Following Single-incision Versus Traditional Laparoscopic Cholecystectomy. AB - BACKGROUND: We undertook a randomized controlled trial to ascertain if single incision laparoscopic cholecystectomy (SILC) was more beneficial for reducing postoperative pain than traditional laparoscopic cholecystectomy (TLC). Moreover, the influencing factors of SILC were analyzed. METHODS: A total of 552 patients with symptomatic gallstones or polyps were allocated randomly to undergo SILC (n = 138) or TLC (n = 414). Data on postoperative pain score, operative time, complications, procedure conversion, and hospital costs were collected. After a 6 month follow-up, all data were analyzed using the intention-to-treat principle. RESULTS: Among SILC group, 4 (2.9%) cases required conversion to TLC. Mean operative time of SILC was significantly longer than that of TLC (58.97 +/- 21.56 vs. 43.38 +/- 19.02 min, P < 0.001). The two groups showed no significant differences in analgesic dose, duration of hospital stay, or cost. Median pain scores were similar between the two groups 7 days after surgery, but SILC-treated patients had a significantly lower median pain score 6 h after surgery (10-point scale: 3 [2, 4] vs. 4 [3, 5], P = 0.009). Importantly, subgroup analyses of operative time for SILC showed that a longer operative time was associated with greater prevalence of pain score >5 (>=100 min: 5/7 patients vs. <40 min, 3/16 patients, P = 0.015). CONCLUSIONS: The primary benefit of SILC appears to be slightly less pain immediately after surgery. Surgeon training seems to be important because the shorter operative time for SILC may elicit less pain immediately after surgery. PMID- 26668146 TI - Mid- to Long-term Clinical Outcomes of Hancock II Bioprosthesis in Chinese Population. AB - BACKGROUND: Compared to the Western countries, Chinese patients present a special primary disease spectrum, diverse valvular pathogenesis, and different postoperational anticoagulation strategy. This research aimed to evaluate the mid to long-term clinical performance of Hancock II bioprosthesis in the Chinese population. METHODS: This study retrospectively reviewed all patients who received surgical treatments with at least one Hancock II bioprosthesis implantation from January 2004 to December 2013 at a single center in China. Totally 647 patients were included in the clinical evaluation, and 629 patients were successfully discharge, among whom 605 patients were completely followed-up. The follow-up rate was 96.2%. The mean and median follow-up time was 62.0 +/- 59.0 and 56.0 months, respectively. Postoperative outcomes of survival rates, reoperations and valve related morbidities were assessed. Continuous and categorical variables were compared using the t -test and Chi-square test, respectively. Survival and freedom from adverse events were calculated by using a Kaplan-Meier method. RESULTS: The overall in-hospital mortality was 2.8% (18/647) while there were 34 deaths (5.6%, 34/605) in the follow-up stage after discharge. The overall survival rate was 94.6% and 82.7% at 5 years and 10 years, respectively. The cumulative survival rate of 10 years was 82.8% in AVR group, 84.4% in MVR group, and 78.4% in DVR group. The overall rate of freedom from reoperations was 95.5% at 5 years and 86.8% at 10 years. The freedom from reoperation at 10 years was 87.0%, 88.1%, and 84.0% in AVR, MVR, and DVR group, respectively. The freedom from morbidities at 10 years was: 90.3% for thromboembolism, 95.2% for hemorrhage, 97.5% for prosthesis endocarditis, 95.9% for paravalvular leak, and 94.6% for structural valve deterioration, respectively. CONCLUSIONS: Hancock II bioprosthesis exhibited a satisfactory mid- to long-term durability and promising clinical performance in the Chinese population. The occurrence rates of death and other adverse events in this single center study were overall coincident and quite acceptable when compared with existing data. PMID- 26668147 TI - Chinese Internet Searches Provide Inaccurate and Misleading Information to Epilepsy Patients. AB - BACKGROUND: Most patients with epilepsy want to learn as much as possible about the disease, and many have turned to the internet for information. Patients are likely to use information obtained from the internet to control their epilepsy, but little is known about the accuracy of this information. In this survey, we have assessed the feasibility and usability of internet-based interventions for the treatment of epilepsy. METHODS: Data were collected from an internet search. Different search terms were used to obtain general information on epilepsy together with information about medication, types of epilepsy, treatment, women's health, and other information. The accuracy of the information was evaluated by a group of experts. RESULTS: A total of 1320 web pages were assessed. The majority were websites related to health. A large number (80.2%) of web pages contained content related to the search term. A significant number of web pages 450/1058 (42.5%) claimed to provide information from a credible source; however, only 206/1058 (19.5%) of the information was accurate and complete; 326/1058 (30.8%) was accurate but incomplete; 328/1058 (31.0%) was correct but nonstandard, and 198/1058 (18.8%) was inaccurate. The authenticity of the information was not significantly different between the two search engines (chi2 = 0.009, P = 0.924). No significant difference was observed in the information obtained from a specialist or nonspecialist source (chi2 = 7.538, P = 0.057). There was also no correlation between the quality of the information and the priority (chi2 = 6.880, P = 0.076). CONCLUSIONS: Searching for information about epilepsy on the internet is convenient, but the information provided is not reliable. Too much information is inaccurate or for advertisement purposes, and it is difficult for patients to find the useful information. Turning to the internet for medical knowledge may be harmful. Physicians should be aware that their patients may search for information on the internet and guide them to safe, reputable websites. PMID- 26668148 TI - Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction. AB - BACKGROUND: Work in voiding (WIV) of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO). METHODS: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (PdetQmax) of >=40 cmH2O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t) and WIV per liter of urine voided (WIV/v) were also calculated. In men, the relationships between these work capacity parameters and PdetQmax and Abrams-Griffiths (AG) number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman's association test. RESULTS: The mean WIV was 1.15 +/ 0.78 J and 1.30 +/- 0.88 J, mean WIV/t was 22.95 +/- 14.45 mW and 23.78 +/- 17.02 mW, and mean WIV/v was 5.59 +/- 2.32 J/L and 2.83 +/- 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with PdetQmax (r = 0.845, P = 0.000), AG number (r = 0.814, P = 0.000), and Schafer class (r = 0.726, P = 0.000). Conversely, WIV and WIV/t showed no associations with PdetQmax or AG number. In patients with BOO (Schafer class > II), WIV/v correlated positively with increasing BOO grade. CONCLUSIONS: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t. PMID- 26668149 TI - Impact and Clinical Predictors of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors. AB - BACKGROUND: The optimal surgical management of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is still controversial. Here, we evaluated the impact of lymph node status on postoperative recurrence in patients with NF-PNET and the potential of preoperative variables for predicting lymph node metastasis (LNM). METHODS: In this mono-institutional retrospective cohort study conducted in 100 consecutive patients who underwent NF-PNET resection between January 2004 and December 2014, we evaluated risk factors for survival using the Kaplan-Meier method and the Cox regression model. Predictors of LNM were evaluated using the logistic regression model, and the power of predictive models was evaluated using receiver operating characteristic curve analysis. RESULTS: Five-year disease-free survival of resected NF-PNET was 64.1%. LNM was independently associated with postoperative recurrence (hazard ratio = 3.995, P = 0.003). Multivariate analysis revealed tumor grade as an independent factor associated with LNM (G2 vs. G1: odds ratio [OR] =6.287, P = 0.008; G3 vs. G1: OR = 12.407, P = 0.001). When tumor grade was excluded, radiological tumor diameter >2.5 cm (OR = 5.430, P = 0.013) and presence of symptoms (OR = 3.366, P = 0.039) were significantly associated with LNM. Compared to neoplasms with radiological diameter >2.5 cm (32.1%), tumors <=2.5 cm had an obviously lower risk of LNM (7.7%), indicating the reliability of this parameter in predicting LNM (area under the curve, 0.693). Incidentally discovered NF-PNETs <=2.5 cm were associated with a low-risk of LNM and excellent survival. CONCLUSIONS: LNM is significantly associated with postoperative recurrence. Radiological tumor diameter is a reliable predictor of LNM in NF-PNETs. Our results indicate that lymphadenectomy in small (<=2.5 cm) NF PNETs is not routinely necessary. PMID- 26668150 TI - Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment. AB - BACKGROUND: There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI. METHODS: To decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years. RESULTS: We identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient. CONCLUSIONS: We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases. PMID- 26668151 TI - Femoral Condyles Tangential Views: An Effective Method to Detect the Screw Penetration of Femoral Condyles After Retrograde Nailing. AB - BACKGROUND: Postoperative knee soft tissue irritation is a common complication after retrograde nail fixation of femoral fractures. Distal locking screw prominence is one of the causes for soft tissue irritation. This study aimed to determine whether the use of the femoral condyles tangential views improve the diagnostic accuracy compared with anteroposterior (A-P) view in detecting distal locking screw penetrations during retrograde femoral nailing. METHODS: The angle between the sagittal plane and lateral aspect of the condyle and the angle between the sagittal plane and medial aspect of condyle were measured on computed tomography (CT) images. After the angles were measured and recorded, cadaveric femurs were used in a simulated surgical procedure. The retrograde femoral nail was inserted into the femur and placed distal locking screws, which were left 2, 4, and 6 mm proud of the medial and lateral condyles for each femur. A-P view, lateral condyle tangential view and medial condyle tangential view were obtained. All fluoroscopic images were recorded and sent to three observers blinded to the experimental procedure to determine whether screws penetrated the condyle cortex or not. RESULTS: According to the results of CT scan, the lateral condyle view was 20.88 +/- 0.98 degrees and the medial condyle view was 40.46 +/- 3.14 degrees . In the A-P view, we detected 0% at 2 mm penetration, 16.7% (lateral condyle screw) and 25.0% (medial condyle screw) at 4 mm, and 41.7% (lateral condyle screw) and 58.3% (medial condyle screw) at 6 mm. In the lateral tangential view, we detected 91.7% at 2 mm penetration of the lateral condyle and 100% at 4 mm and 6 mm. In the medial tangential view, we detected 66.7% at 2 mm penetration of the medial condyle and 100% at 4 mm and 6 mm. The femoral condyle tangential views provided significant improvement in detecting screw penetrations at all lengths (2, 4, and 6 mm) compared with the A-P view (P < 0.05). CONCLUSIONS: The femoral condyles tangential views increased the accuracy of detecting screw penetrations on the medial and lateral condyles. Routine clinical use of the femoral condyles tangential views has the potential to increase accuracy in detecting distal locking screw penetration during retrograde femoral nailing. PMID- 26668152 TI - A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia. AB - BACKGROUND: Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells (EPCs) derived from human early fetal aortas in rat injured arteries. METHODS: The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas (<14 weeks) were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. RESULTS: Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control (P < 0.05) and the residual lumen area was larger (P < 0.05). After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human von Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. CONCLUSION: EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury. PMID- 26668153 TI - Research Progress of MicroRNA in Early Detection of Ovarian Cancer. AB - OBJECTIVE: This review aimed to update the progress of microRNA (miRNA) in early detection of ovarian cancer. We discussed the current clinical diagnosis methods and biomarkers of ovarian cancer, especially the methods of miRNA in early detection of ovarian cancer. DATA SOURCES: We collected all relevant studies about miRNA and ovarian cancer in PubMed and CNKI from 1995 to 2015. STUDY SELECTION: We included all relevant studies concerning miRNA in early detection of ovarian cancer, and excluded the duplicated articles. RESULTS: miRNAs play a key role in various biological processes of ovarian cancer, such as development, proliferation, differentiation, apoptosis and metastasis, and these phenomena appear in the early-stage. Therefore, miRNA can be used as a new biomarker for early diagnosis of ovarian cancer, intervention on miRNA expression of known target genes, and potential target genes can achieve the effect of early prevention. With the development of nanoscience and technology, analysis methods of miRNA are also quickly developed, which may provide better characterization of early detection of ovarian cancer. CONCLUSIONS: In the near future, miRNA therapy could be a powerful tool for ovarian cancer prevention and treatment, and combining with the new analysis technology and new nanomaterials, point-of-care tests for miRNA with high throughput, high sensitivity, and strong specificity are developed to achieve the application of diagnostic kits in screening of early ovarian cancer. PMID- 26668155 TI - Charcot Elbow Joint as the Initial Symptom in Chiari Malformation with Syringomyelia. PMID- 26668154 TI - Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease. AB - OBJECTIVE: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). DATA SOURCES: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. STUDY SELECTION: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. RESULTS: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. CONCLUSIONS: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients. PMID- 26668156 TI - Acute Cerebral Thrombosis Following Ovarian Hyperstimulation Syndrome: A Case Report. PMID- 26668157 TI - Does Anemia Cause QT Prolongation in Patients with Hematologic Disorders? PMID- 26668158 TI - May Hips with Inflammatory Synovial Tissue Bands Worsen the Symptoms of Femoroacetabular Impingement Patients? A Two-case Report. PMID- 26668160 TI - Corrigendum: Obstructive Sleep Apnea Syndrome is Associated with Metabolic Syndrome Among Adolescents and Youth in Beijing: Data from Beijing Child and Adolescent Metabolic Syndrome Study. PMID- 26668159 TI - Ectopic Thyroid Masquerading as Pituitary Adenoma. PMID- 26668161 TI - Online "living will" tool is launched to help ensure that people's care wishes are respected. PMID- 26668162 TI - The Use of Cerebral Oximetry in Acute Carbon Monoxide Intoxication: A Preliminary Study. AB - The purpose of this study was to assess the clinical usefulness of near-infrared spectroscopy (cerebral oximetry) in patients presenting to the emergency department (ED) with carbon monoxide (CO) intoxication. Eighteen patients with a diagnosis of CO intoxication who presented to our ED during 2013 were included in this prospective study. All patients were treated and monitored according to the standard recommendations for CO intoxication. In addition, cerebral oxygen saturation (ScO2) was measured using near-infrared spectroscopy, also known as cerebral oximetry. Minimum and maximum ScO2 values from the right and left frontal region were recorded using cerebral oximetry from immediately after presentation to the ED until discharge. Patient blood carboxyhemoglobin (COHb) levels before and after oxygen treatment were compared with the cerebral oximetry measurements. At the time of admission, mean blood (COHb) values were 29.3% +/- 6.7%, and ScO2 values were 59.0 +/- 4.0 in the right frontal region and 60.9 +/- 5.1 in the left. When blood COHb levels had returned to normal following oxygen therapy, ScO2 values were 75.9 +/- 6.1 (65.5-90.5) in the right frontal region and 74.9 +/- 7.8 (62.0-90.0) in the left. The differences in ScO2 values before and after oxygen therapy were statistically significant (P <= 0.005). Assessment of patients exposed to CO gas using cerebral oximetry can provide information about cerebral oxygen saturation. Blood COHb level measurement is still the best method for diagnosing CO intoxication; however, cerebral oximetry, a non-invasive technique, may be an effective method for assessing cerebral oxygen saturation. PMID- 26668164 TI - Histological and immunohistochemical studies on primary intracranial canine histiocytic sarcomas. AB - Histiocytic sarcoma is a progressive and fatal malignant neoplasm that mainly occurs in middle- to old-aged dogs. This study describes clinicopathological, histological and immunohistochemical characteristics of intracranial histiocytic sarcomas in 23 dogs. Magnetic resonance imaging and/or computed tomography of the brains revealed that the tumors mainly located in the cerebrum, particularly the frontal lobe. Seizure was a predominant clinical sign in most of the cases. Histologically, the tumor cells were morphologically classified into round/polygonal- and spindle-shaped cell types. There was a significant association between tumor cell types and hemophagocytic activity (P<0.05). However, there was no significant difference in other clinicopathological parameters and mitotic index between the 2 types. Immunohistochemically, tumor cells were strongly positive for HLA-DR, Iba-1 and CD204 in all the 23 cases, for iNOS in 20, for CD163 in 17, for CD208 (DC-LAMP) in 9, for lysozyme in 8 and for S100 in 5 cases. In addition, the Ki67-proliferative index showed range of 0.50 64.33% (Average 26.60 +/- 3.81%). These observations suggest that canine primary intracranial histiocytic sarcomas tend to exhibit both dendritic cell and macrophage phenotypes of histiocytic differentiation. PMID- 26668165 TI - First isolation of Actinobacillus genomospecies 2 in Japan. AB - We describe here the first isolation of Actinobacillus genomospecies 2 in Japan. The isolate was found in a septicemic foal and characterized by phenotypic and genetic analyses, with the latter consisting of 16S rDNA nucleotide sequence analysis plus multilocus sequence analysis using three housekeeping genes, recN, rpoA and thdF, that have been proposed for use as a genomic tool in place of DNA DNA hybridization. PMID- 26668163 TI - Genome-wide identification and characterization of transcription start sites and promoters in the tunicate Ciona intestinalis. AB - The tunicate Ciona intestinalis, an invertebrate chordate, has recently emerged as a powerful model organism for gene regulation analysis. However, few studies have been conducted to identify and characterize its transcription start sites (TSSs) and promoters at the genome-wide level. Here, using TSS-seq, we identified TSSs at the genome-wide scale and characterized promoters in C. intestinalis. Specifically, we identified TSS clusters (TSCs), high-density regions of TSS-seq tags, each of which appears to originate from an identical promoter. TSCs were found not only at known TSSs but also in other regions, suggesting the existence of many unknown transcription units in the genome. We also identified candidate promoters of 79 ribosomal protein (RP) genes, each of which had the major TSS in a polypyrimidine tract and showed a sharp TSS distribution like human RP gene promoters. Ciona RP gene promoters, however, did not appear to have typical TATA boxes, unlike human RP gene promoters. In Ciona non-RP promoters, two pyrimidine purine dinucleotides, CA and TA, were frequently used as TSSs. Despite the absence of CpG islands, Ciona TATA-less promoters showed low expression specificity like CpG-associated human TATA-less promoters. By using TSS-seq, we also predicted trans-spliced gene TSSs and found that their downstream regions had higher G+T content than those of non-trans-spliced gene TSSs. Furthermore, we identified many putative alternative promoters, some of which were regulated in a tissue-specific manner. Our results provide valuable information about TSSs and promoter characteristics in C. intestinalis and will be helpful in future analysis of transcriptional regulation in chordates. PMID- 26668166 TI - Emphysematous pyonephrosis associated with extrahepatic portosystemic shunt in a dog. AB - A 16-month-old intact female Maltese dog was referred for examination of depression and vomiting. Ultrasonography revealed dilated right renal pelvis containing echogenic fluid with free gas. A hyperechoic material suspected of urolith was identified in the right ureter. Computed tomography revealed emphysematous change of the right kidney associated with ureteral obstruction and extrahepatic portosystemic shunt (EHPSS). Ureteronephrectomy and surgical correction were performed for the EHPSS. Escherichia coli was isolated from pus from the right kidney. Quantitative analysis revealed that the urolith was an ammonium urate stone. After 5 months follow-up, no complication was observed. This is the first report of emphysematous pyonephrosis associated with EHPSS in a dog. PMID- 26668167 TI - Addiction, Autonomy, and Informed Consent: On and Off the Garden Path. AB - Several ethicists have argued that research trials and treatment programs that involve the provision of drugs to addicts are prima facie unethical, because addicts can't refuse the offer of drugs and therefore can't give informed consent to participation. In response, several people have pointed out that addiction does not cause a compulsion to use drugs. However, since we know that addiction impairs autonomy, this response is inadequate. In this paper, I advance a stronger defense of the capacity of addicts to participate in the programs envisaged. I argue that it is only in certain circumstances that addicts find themselves choosing in ways that conflict with their genuine preferences. Research and treatment programs have none of the features that characterize choices in these autonomy-undermining circumstances, and there is therefore no reason to think that addicts lack the capacity to give informed consent to these programs. PMID- 26668168 TI - Autonomy, Trust, and Respect. AB - This article seeks to explore and analyze the relationship between autonomy and trust, and to show how these findings could be relevant to medical ethics. First, I will argue that the way in which so-called "relational autonomy theories" tie the notions of autonomy and trust together is not entirely satisfying Then, I will introduce the so-called Encapsulated Interest Account as developed by Russell Hardin. This will bring out the importance of the reasons for trust. What good reasons do we have for trusting someone? I will criticize Hardin's business model as insufficiently robust, especially in the context of health care, and then turn to another source of trust, namely, love. It may seem that trust through-love is much better suited for the vulnerability that is often involved in health care, but I will also show that it has its own deficiencies. Good health care should therefore pay attention to both models of trust, and I will offer some tentative remarks on how to do this. PMID- 26668169 TI - 2015 ASCB Annual Meeting abstracts. PMID- 26668171 TI - Evolutionary cell biology: functional insight from "endless forms most beautiful". AB - In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. PMID- 26668172 TI - What cell biologists should know about the National Institutes of Health BRAIN Initiative. AB - The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role. PMID- 26668173 TI - Debunking the curse of the rainbow jersey: historical cohort study. AB - OBJECTIVE: To understand the underlying mechanism of the "curse of the rainbow jersey," the lack of wins that purportedly affects the current cycling world champion. DESIGN: Historical cohort study. SETTING: On the road. PARTICIPANTS: Professional cyclists who won the World Championship Road Race or the Tour of Lombardy, 1965-2013. MAIN OUTCOME MEASURES: Number of professional wins per season in the year when the target race was won (year 0) and in the two following years (years 1 and 2; the world champion wears the rainbow jersey in year 1). The following hypotheses were tested: the "spotlight effect" (that is, people notice when a champion loses), the "marked man hypothesis" (the champion, who must wear a visible jersey, is marked closely by competitors), and "regression to the mean" (a successful season will be generally followed by a less successful one). RESULTS: On average, world champions registered 5.04 wins in year 0, 3.96 in year 1, and 3.47 in year 2; meanwhile, winners of the Tour of Lombardy registered 5.08, 4.22, and 3.83 wins. In a regression model that accounted for the propensity to win of each rider, the baseline year accrued more wins than did the other years (win ratio 1.49, 95% confidence interval 1.24 to 1.80), but the year in the rainbow jersey did not differ significantly from other cycling seasons. CONCLUSIONS: The cycling world champion is significantly less successful during the year when he wears the rainbow jersey than in the previous year, but this is best explained by regression to the mean, not by a curse. PMID- 26668170 TI - The cell biology of aging. AB - One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal--a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part genetically regulated. Many mutations have been discovered to extend lifespan in organisms of all complexities, from yeast to mammals. The study of metazoan model organisms, such as Caenorhabditis elegans, has been instrumental in understanding the role of genetics in the cell biology of aging. Longevity mutants across the spectrum of model organisms demonstrate that rates of aging are regulated through genetic control of cellular processes. The regulation and subsequent breakdown of cellular processes represent a programmatic decision by the cell to either continue or abandon maintenance procedures with age. Our understanding of cell biological processes involved in regulating aging have been particularly informed by longevity mutants and treatments, such as reduced insulin/IGF-1 signaling and dietary restriction, which are critical in determining the distinction between causes of and responses to aging and have revealed a set of downstream targets that participate in a range of cell biological activities. Here we briefly review some of these important cellular processes. PMID- 26668174 TI - Intrapulmonary concentration of enrofloxacin in healthy calves. AB - To determine the intrapulmonary concentration of enrofloxacin (ERFX) in calves, plasma, bronchoalveolar lavage fluid (BALF) and alveolar cells samples were obtained from clinically healthy calves. Four clinically healthy calves were administered a single dose of ERFX (5 mg/kg) by subcutaneous injection. Samples of plasma were obtained for each subjects at 0 (before administration), 1 and 2 hr after administration of ERFX. Samples of BALF were obtained from each subject at 0, 1 and 2 hr after administration of ERFX. This examination was conducted two times, one week apart. The mean EFRX concentrations in plasma at 1 and 2 hr after administration were l.23 and 1.29 ug/ml, respectively. The mean EFRX concentrations in pulmonary epithelial lining fluid (ELF) at 1 and 2 hr after administration 8.53 ug/ml and 9.42 ug/ml, respectively. The mean ERFX concentrations of alveolar cells in BALF at 1 and 2 hr after administration were 4.04 ug/ml and 5.19 ug/ml, respectively. These results suggest that the ERFX concentrations in ELF and alveolar cells concentrations in BALF at 1 and 2 hr after administration were higher than the plasma concentrations. PMID- 26668175 TI - A recombinant nucleocapsid protein-based indirect enzyme-linked immunosorbent assay to detect antibodies against porcine deltacoronavirus. AB - Recently, porcine deltacoronavirus (PDCoV) has been proven to be associated with enteric disease in piglets. Diagnostic tools for serological surveys of PDCoV remain in the developmental stage when compared with those for other porcine coronaviruses. In our study, an indirect enzyme-linked immunosorbent assay (ELISA) (rPDCoV-N-ELISA) was developed to detect antibodies against PDCoV using a histidine-tagged recombinant nucleocapsid (N) protein as an antigen. The rPDCoV-N ELISA did not cross-react with antisera against porcine epidemic diarrhea virus, swine transmissible gastroenteritis virus, porcine group A rotavirus, classical swine fever virus, porcine circovirus-2, porcine pseudorabies virus, and porcine reproductive and respiratory syndrome virus; the receiver operating characteristic (ROC) curve analysis revealed 100% sensitivity and 90.4% specificity of the rPDCoV-N-ELISA based on samples of known status (n=62). Analyses of field samples (n=319) using the rPDCoV-N-ELISA indicated that 11.59% of samples were positive for antibodies against PDCoV. These data demonstrated that the rPDCoV-N-ELISA can be used for epidemiological investigations of PDCoV and that PDCoV had a low serum prevalence in pig population in Heilongjiang province, northeast China. PMID- 26668178 TI - Examining the Impact of Maternal Health, Race, and Socioeconomic Status on Daughter's Self-Rated Health Over Three Decades. AB - This study examines the role of mother's health and socioeconomic status on daughter's self-rated health using data spanning three decades from the National Longitudinal Surveys of Mature Women and Young Women (N = 1,848 matched mother daughter pairs; 1,201 White and 647 African American). Using nested growth curve models, we investigated whether mother's self-rated health affected the daughter's self-rated health and whether socioeconomic status mediated this relationship. Mother's health significantly influenced daughters' self-rated health, but the findings were mediated by mother's socioeconomic status. African American daughters reported lower self-rated health and experienced more decline over time compared with White daughters, accounting for mother's and daughter's covariates. Our findings reveal maternal health and resources as a significant predictor of daughters' self-rated health and confirm the role of socioeconomic status and racial disparities over time. PMID- 26668179 TI - The Productivity of Wh- Prompts in Child Forensic Interviews. AB - Child witnesses are often asked wh- prompts (what, how, why, who, when, where) in forensic interviews. However, little research has examined the ways in which children respond to different wh- prompts, and no previous research has investigated productivity differences among wh- prompts in investigative interviews. This study examined the use and productivity of wh- prompts in 95 transcripts of 4- to 13-year-olds alleging sexual abuse in child investigative interviews. What-how questions about actions elicited the most productive responses during both the rapport building and substantive phases. Future research and practitioner training should consider distinguishing among different wh- prompts. PMID- 26668177 TI - Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial. AB - BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. PMID- 26668180 TI - Incidence and Outcomes of Dating Violence Victimization Among High School Youth: The Role of Gender and Sexual Orientation. AB - The purpose of this study was to examine rates of dating violence (DV) victimization and DV victimization outcomes as a function of sex and sexual orientation. Participants were 25,122 high school students who participated in the 2013 New Hampshire Youth Risk Behavior Survey study. Heterosexual youth, especially heterosexual male youth, were less likely to report experiencing physical and sexual DV victimization than lesbian, gay, bisexual, and questioning (LGBQ) girls and boys. Among LGBQ girls and boys, there was little variability in rates of DV victimization with the exception of questioning boys being significantly more likely to experience physical and sexual DV victimization than several other LGBQ sub-groups. Furthermore, LGBQ DV victims reported worse outcomes than heterosexual DV victims on measures of depression, binge drinking, and poor academic performance. At the sub-group level, bisexual and questioning female victims were most at risk for depression; bisexual and questioning male victims were most at risk for binge drinking; bisexual male victims were most at risk for poor academic performance. The findings underscore the importance of better understanding variability in DV incidence and outcomes within the LGBQ population and using this information to inform clinical intervention and prevention efforts. PMID- 26668181 TI - When childhood ends: estimating the age of young people. PMID- 26668182 TI - Mutual Influence and Older Married Adults' Anxiety Symptoms: Results From The Irish Longitudinal Study on Ageing. AB - Purpose of the Study: This study analyzed dyadic data to examine the direct and indirect associations between husbands' and wives' reports of marital strain and generalized anxiety symptoms in later life. Design and Methods: Data were from 1,114 married couples with at least one spouse aged 60 or older, drawn from the initial 2009-2011 wave of The Irish Longitudinal Study on Ageing. Structural equation modeling was used to analyze dyadic data according to individual influence and mutual influence frameworks. Results: Mutual influence exhibited better model fit than individual influence. Findings revealed that perceptions of marital strain were related with husbands' and wives' own generalized anxiety symptoms. Further, husbands' anxiety symptoms were significantly related with wives' anxiety symptoms, and vice versa, illustrating bidirectional feedback. Finally, husbands' and wives' perceptions of marital strain were significantly indirectly related with their partners' anxiety symptoms, with these associations being mediated by spouses' own anxiety symptoms. Implications: Anxiety is a relational experience and may even be provoked by one's marriage. Mutual influence modeling indicated that husbands' and wives' perceptions of the marriage and reports of anxiety were influential for both spouses' anxiety symptoms. These results suggest that emotional contagion may be the pathway for partner effects of marital strain on spouses' well-being. Findings also suggest that efforts to reduce anxiety symptoms may be most effective when taking marital context and quality into account. PMID- 26668183 TI - Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance. AB - The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naive hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance. PMID- 26668185 TI - Toward Automated Interpretation of LC-MS Data for Quality Assurance of a Screening Collection. AB - The AstraZeneca Compound Management group uses high-performance liquid chromatography-mass spectrometry for structure elucidation and purity determination of the AstraZeneca compound collection. These activities are conducted in a high-throughput environment where the rate-limiting step is the review and interpretation of analytical results, which is time-consuming and experience dependent. Despite the development of a semiautomated review system, manual interpretation of results remains a bottleneck. Data-mining techniques were applied to archived data to further automate the review process. Various classification models were evaluated using WEKA and Pipeline Pilot (Pipeline Pilot version 8.5.0.200, BIOVIA, San Diego, CA). Results were assessed using criteria including precision, recall, and receiver operating characteristic area. Each model was evaluated as a cost-insensitive classifier and again using MetaCost to apply cost sensitivity. Pruning and variable importance were also investigated. A 10-tree random forest generated with Pipeline Pilot reduced the number of analyses requiring manual review to 36.4% using a threshold of 90% confidence in predictions. This represents a 45% reduction in manual reviews compared with the previous system, delivering an annual savings of $45,000 or an increase in capacity from 25,000 analyses per month up to 45,000 with the same resource levels. PMID- 26668186 TI - Up to half of people shot dead by US police may have untreated mental illness, report estimates. PMID- 26668184 TI - TERT Promoter Mutations and Risk of Recurrence in Meningioma. AB - The World Health Organization (WHO) classification and grading system attempts to predict the clinical course of meningiomas based on morphological parameters. However, because of high interobserver variation of some criteria, more reliable prognostic markers are required. Here, we assessed the TERT promoter for mutations in the hotspot regions C228T and C250T in meningioma samples from 252 patients. Mutations were detected in 16 samples (6.4% across the cohort, 1.7%, 5.7%, and 20.0% of WHO grade I, II, and III cases, respectively). Data were analyzed by t test, Fisher's exact test, log-rank test, and Cox proportional hazard model. All statistical tests were two-sided. Within a mean follow-up time in surviving patients of 68.1 months, TERT promoter mutations were statistically significantly associated with shorter time to progression (P < .001). Median time to progression among mutant cases was 10.1 months compared with 179.0 months among wild-type cases. Our results indicate that the inclusion of molecular data (ie, analysis of TERT promoter status) into a histologically and genetically integrated classification and grading system for meningiomas increases prognostic power. Consequently, we propose to incorporate the assessment of TERT promoter status in upcoming grading schemes for meningioma. PMID- 26668187 TI - Gender Disparity in the Safety and Efficacy of Radial and Femoral Access for Coronary Intervention: A Systematic Review and Meta-Analysis. AB - Our aim was to investigate the gender disparity in the safety and efficacy of transradial percutaneous coronary intervention (PCI; TRI) and transfemoral PCI (TFI) by a meta-analysis. MEDLINE, Embase, and CENTRAL were searched to identify studies on vascular access with sex-specific events available or studies on sex difference with the events reported by vascular access. Fifteen studies involving 3 921 848 participants were included. Transradial PCI significantly reduced the risk of bleeding complications in both sexes (TRI-versus-TFI odds ratio [OR]: 0.37 in females vs 0.47 in males) and major adverse cardiac events (MACE) in females (OR: 0.70, P < .001) but not in males (OR: 0.83, P = .15) compared to TFI. Transradial PCI diminished the sex difference in the incidence of bleeding complications (female-versus-male OR: 1.82 with TRI vs 2.39 with TFI; interaction P = .01) and MACE (female-versus-male OR: 1.21 with TRI vs 1.41 with TFI; interaction P = .003) compared to TFI. Females were associated with higher crossover rate in the TRI subgroup but not in the TFI subgroup (interaction P = .05). In conclusion, TRI may improve the safety and efficacy of outcomes in both sexes and be an effective means to cut down the gender difference in prognosis. PMID- 26668188 TI - Safe Exclusion of Deep Vein Thrombosis by a Rapid Sensitive ELISA D-dimer and Compression Ultrasonography in 1330 Outpatients With Suspected DVT. AB - Of 1330 outpatients with suspected deep vein thrombosis (DVT), a normal enzyme linked immunosorbent assay (ELISA) d-dimer (VIDAS) of <500 ng/mL was true negative in 382 of 384 and false negative in compression ultrasonography (CUS) in 2, indicating a sensitivity of 99.52% and a negative predictive value (NPV) of 99.48%, with a specificity of 36% irrespective of clinical score. In 1059 outpatients with no DVT, the CUS was positive for the alternative diagnoses (AD): Bakers cyst, muscle hematoma, or old DVT in 62 (5.8%); superficial vein thrombosis without DVT in 78 (7.4%), and leg edema or varices in 17%. A second CUS in 641 patients was positive in 26 (4.0%), indicating an NPV of 96% after a first negative CUS. The NPV of the combination of a negative first CUS and a ELISA d-dimer test <1000 ng/mL was 99.1% at a specificity of 66.9%. As this strategy is cost effective by reduction in the need to repeat CUS by 67%, we designed a novel algorithm for the safe exclusion and diagnosis of DVT and AD for subsequent evaluation in a large prospective study. PMID- 26668190 TI - Preparing for the arrival of "pink Viagra": strengthening Canadian direct-to consumer information regulations. PMID- 26668191 TI - Medical certificates of death: First principles and established practices provide answers to new questions. PMID- 26668192 TI - What's next for the Liberals on health? PMID- 26668189 TI - A Novel Inhibitor of Topoisomerase I Is Selectively Toxic for a Subset of Non Small Cell Lung Cancer Cell Lines. AB - SW044248, identified through a screen for chemicals that are selectively toxic for non-small cell lung cancer (NSCLC) cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive, cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was nontoxic to immortalized human bronchial cell lines. The acute transcriptional response to SW044248 in sensitive HCC4017 cells correlated significantly with inhibitors of topoisomerases and SW044248 inhibited topoisomerase 1 (Top1) but not topoisomerase 2. SW044248 inhibited Top1 differently from camptothecin and camptothecin did not show the same selective toxicity as SW044248. Elimination of Top1 by siRNA partially protected cells from SW044248, although removing Top1 was itself eventually toxic. Cells resistant to SW044248 responded to the compound by upregulating CDKN1A and siRNA to CDKN1A sensitized those cells to SW044248. Thus, at least part of the differential sensitivity of NSCLC cells to SW044248 is the ability to upregulate CDKN1A. PMID- 26668193 TI - The other side. PMID- 26668195 TI - Provinces optimistic for health accord talks. PMID- 26668194 TI - Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. PMID- 26668196 TI - Endovascular thrombectomy in acute ischemic stroke. PMID- 26668197 TI - Dark forecast for mental health in Alberta. PMID- 26668198 TI - Harm reduction over morals to reduce smoking deaths. PMID- 26668199 TI - Constipation in a 40-year-old woman. PMID- 26668201 TI - Hominid spongyform encephalophagy: cooking time 1-11/2 hours, difficulty ***. PMID- 26668200 TI - Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial. AB - BACKGROUND: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient important outcomes were assessed up to 6 months after randomization. RESULTS: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01071265. PMID- 26668202 TI - Recovery from an acute relapse is associated with changes in motor resting-state connectivity in multiple sclerosis. PMID- 26668203 TI - Non-invasive brain stimulation for stroke recovery: ready for the big time? PMID- 26668204 TI - Clinical and Economic Impact of Formulary Conversion From Inhaled Flolan to Inhaled Veletri for Refractory Hypoxemia in Critically Ill Patients. AB - BACKGROUND: Flolan (iFLO) and Veletri (iVEL) are 2 inhaled epoprostenol formulations. There is no published literature comparing these formulations in critically ill patients with refractory hypoxemia. OBJECTIVE: To compare efficacy, safety, and cost outcomes in patients who received either iFLO or iVEL for hypoxic respiratory failure. METHODS: This was a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iFLO or iVEL for improvement in oxygenation. The primary end point was the change in the PaO2/FiO2 ratio after 1 hour of pulmonary vasodilator therapy. Secondary end points assessed were intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of study therapy, duration of mechanical ventilation, mortality, incidence of adverse events, and cost. RESULTS: A total of 104 patients were included (iFLO = 52; iVEL = 52). More iFLO patients had acute respiratory distress syndrome compared with the iVEL group (61.5 vs 34.6%; P = 0.01). There was no difference in the change in the PaO2/FiO2 ratio after 1 hour of therapy (33.04 +/- 36.9 vs 31.47 +/- 19.92; P = 0.54) in the iFLO and iVEL groups, respectively. Patients who received iVEL had a shorter duration of mechanical ventilation (P < 0.001) and ICU LOS (P < 0.001) but not hospital LOS (P = 0.86) and duration of therapy (P = 0.36). No adverse events were attributed to pulmonary vasodilator therapy, and there was no difference in cost. CONCLUSIONS: We found no difference between iFLO and iVEL when comparing the change in the PaO2/FiO2 ratio, safety, and cost in hypoxic, critically ill patients. There were differences in secondary outcomes, likely a result of differences in underlying indication for inhaled epoprostenol. PMID- 26668205 TI - Empathy and Theory of Mind in Deaf and Hearing Children. AB - Empathy (or sharing another's emotion) and theory of mind (ToM: the understanding that behavior is guided by true and false beliefs) are cornerstones of human social life and relationships. In contrast to ToM, there has been little study of empathy's development, especially in deaf children. Two studies of a total of 117 children (52 hearing; 65 deaf children of hearing parents) aged 4-13 years were therefore designed to (a) compare levels of empathy in deaf and hearing children, and (b) explore correlations of ToM with empathy in deaf and hearing groups. Results showed that (a) deaf children scored lower in empathy than their hearing peers and (b) empathy and ToM were significantly correlated for deaf children but not for the hearing. Possible reasons for these divergent developmental patterns were considered, along with implications for future research. PMID- 26668206 TI - Use of positive and negative words in scientific PubMed abstracts between 1974 and 2014: retrospective analysis. AB - OBJECTIVE: To investigate whether language used in science abstracts can skew towards the use of strikingly positive and negative words over time. DESIGN: Retrospective analysis of all scientific abstracts in PubMed between 1974 and 2014. METHODS: The yearly frequencies of positive, negative, and neutral words (25 preselected words in each category), plus 100 randomly selected words were normalised for the total number of abstracts. Subanalyses included pattern quantification of individual words, specificity for selected high impact journals, and comparison between author affiliations within or outside countries with English as the official majority language. Frequency patterns were compared with 4% of all books ever printed and digitised by use of Google Books Ngram Viewer. MAIN OUTCOME MEASURES: Frequencies of positive and negative words in abstracts compared with frequencies of words with a neutral and random connotation, expressed as relative change since 1980. RESULTS: The absolute frequency of positive words increased from 2.0% (1974-80) to 17.5% (2014), a relative increase of 880% over four decades. All 25 individual positive words contributed to the increase, particularly the words "robust," "novel," "innovative," and "unprecedented," which increased in relative frequency up to 15,000%. Comparable but less pronounced results were obtained when restricting the analysis to selected journals with high impact factors. Authors affiliated to an institute in a non-English speaking country used significantly more positive words. Negative word frequencies increased from 1.3% (1974-80) to 3.2% (2014), a relative increase of 257%. Over the same time period, no apparent increase was found in neutral or random word use, or in the frequency of positive word use in published books. CONCLUSIONS: Our lexicographic analysis indicates that scientific abstracts are currently written with more positive and negative words, and provides an insight into the evolution of scientific writing. Apparently scientists look on the bright side of research results. But whether this perception fits reality should be questioned. PMID- 26668207 TI - Social media-based civic engagement solutions for dengue prevention in Sri Lanka: results of receptivity assessment. AB - This article focuses on a novel social media-based system that addresses dengue prevention through an integration of three components: predictive surveillance, civic engagement and health education. The aim was to conduct a potential receptivity assessment of this system among smartphone users in the city of Colombo, the epicenter of the dengue epidemic in the island country of Sri Lanka. Grounded in Protection Motivation Theory (PMT) and using a convenience sampling approach, the cross-sectional survey assessed perceived severity (PSe), perceived susceptibility (PSu), perceived response efficacy (PRE), perceived self-efficacy (PSE) and intention-to-use (IU) among 513 individuals. The overall receptivity to the system was high with a score of >4.00 on a five-point scale. Participants belonging to younger, better educated and higher income groups reported significantly better perceptions of the efficaciousness of the system, were confident in their ability to use the system, and planned to use it in the future. PMT variables contributed significantly to regression models predicting IU. We concluded that a social media-based system for dengue prevention will be positively received among Colombo residents and a targeted, strategic health communication effort to raise dengue-related threat perceptions will be needed to encourage greater adoption and use of the system. PMID- 26668209 TI - Evaluation of Ketoconazole and Its Alternative Clinical CYP3A4/5 Inhibitors as Inhibitors of Drug Transporters: The In Vitro Effects of Ketoconazole, Ritonavir, Clarithromycin, and Itraconazole on 13 Clinically-Relevant Drug Transporters. AB - Ketoconazole is a potent CYP3A4/5 inhibitor and, until recently, recommended by the Food and Drug Administration (FDA) and the European Medicines Agency as a strong CYP3A4/5 inhibitor in clinical drug-drug interaction (DDI) studies. Ketoconazole sporadically causes liver injury or adrenal insufficiency. Because of this, the FDA and European Medicines Agency recommended suspension of ketoconazole use in DDI studies in 2013. The FDA specifically recommended use of clarithromycin or itraconazole as alternative strong CYP3A4/5 inhibitors in clinical DDI studies, but many investigators have also used ritonavir as an alternative. Although the effects of these clinical CYP3A4/5 inhibitors on other CYPs are largely established, reports on the effects on the broad range of drug transporter activities are sparse. In this study, the inhibitory effects of ketoconazole, clarithromycin, ritonavir, and itraconazole (and its CYP3A4 inhibitory metabolites, hydroxy-, keto-, and N-desalkyl itraconazole) toward 13 drug transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, P gp, BCRP, MRP2, MRP3, and BSEP) were systematically assessed in transporter expressing HEK-293 cell lines or membrane vesicles. In vitro findings were translated into clinical context with the basic static model approaches outlined by the FDA in its 2012 draft guidance on DDIs. The results indicate that, like ketoconazole, the alternative clinical CYP3A4/5 inhibitors ritonavir, clarithromycin, and itraconazole each have unique transporter inhibition profiles. None of the alternatives to ketoconazole provided a clean inhibition profile toward the 13 drug transporters evaluated. The results provide guidance for the selection of clinical CYP3A4/5 inhibitors when transporters are potentially involved in a victim drug's pharmacokinetics. PMID- 26668208 TI - Minimal impact of age and housing temperature on the metabolic phenotype of Acc2 /- mice. AB - An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12-16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 degrees C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42-54 weeks of age, male WT and Acc2(-/-) mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2(-/-) mice, aged Acc2(-/-) mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95+/-0.02 and 0.92+/-0.02 for WT and Acc2(-/-) mice respectively, P<0.05) and skeletal muscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic-euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2(-/-) mice at 29 degrees C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action. PMID- 26668210 TI - Three weeks among the Korowai people. PMID- 26668212 TI - Building Bridges From Hospital to Home: Understanding the Transition Experience for the Newly Diagnosed Pediatric Oncology Patient. AB - Caregivers of pediatric oncology patients are expected to understand and adhere to a complex medical plan of care while at home; yet little is known about how to assess and evaluate the caregivers' abilities to adequately meet these demands. The purpose of this study was to describe the issues and daily challenges faced by caregivers as they transition from hospital to home after their child's cancer diagnosis. Patients and caregivers received a home visit by an expert pediatric oncology nurse within 72 hours postdischarge after initial diagnosis. The nursing narrative notes from these visits were analyzed using content analysis. Four explanatory themes emerged: (1) "We're doing okay," (2) "This isn't going so well," (3) "I could use a little help with this," and (4) "An RN in the house makes you feel safe and know what is correct." These analyses revealed many caregivers achieved mastery of caring for the child at home; however, an overwhelming majority of caregivers expressed questions or concerns to the nurse during the home visit, even those achieving mastery of care. A home visit by an expert pediatric oncology nurse assisted the caregiver in transitioning to caring for the child at home. Such programs should be considered when planning transition programs from hospital to home. PMID- 26668211 TI - Impact of Caregiving for a Child With Cancer on Parental Health Behaviors, Relationship Quality, and Spiritual Faith: Do Lone Parents Fare Worse? AB - Caregiving stress has been associated with changes in the psychological and physical health of parents of children with cancer, including both partnered and single parents. While parents who indicate "single" on a demographic checklist are typically designated as single parents, a parent can be legally single and still have considerable support caring for an ill child. Correspondingly, an individual can be married/partnered and feel alone when caring for a child with serious illness. In the current study, we report the results from our exploratory analyses of parent self-reports of behavior changes during their child's treatment. Parents (N = 263) of children diagnosed with cancer were enrolled at 10 cancer centers. Parents reported significant worsening of all their own health behaviors surveyed, including poorer diet and nutrition, decreased physical activity, and less time spent engaged in enjoyable activities 6 to 18 months following their child's diagnosis. More partnered parents found support from friends increased or stayed the same since their child's diagnosis, whereas a higher proportion of lone parents reported relationships with friends getting worse. More lone parents reported that the quality of their relationship with the ill child's siblings had gotten worse since their child's diagnosis. Spiritual faith increased for all parents. PMID- 26668213 TI - Caregiver Sexual and HPV Communication Among Female Survivors of Childhood Cancer. AB - Human papillomavirus (HPV) vaccination is recommended for all female survivors of childhood cancer; yet, it is underused. Parent-child sexual communication and health care provider recommendation for HPV vaccination influence familial vaccination decisions. However, caregivers may be less likely to discuss sexual health issues with survivors as compared to healthy peers. Therefore, this study compared mothers of daughters with/without history of childhood cancer on measures of sexual communication, HPV-specific communication, and health care provider recommendation for HPV vaccination, and examined the effects of sociodemographic and medical factors on these measures. There were no differences between mothers of survivors/noncancer survivors on the outcomes (Ps > .05). Among all mothers, daughter's age was associated with sexual communication (Ps < .05). Household income and daughter's age were associated with health care provider recommendation for vaccination (Ps < .05). Among mothers of survivors, daughter's age at diagnosis was associated with sexual communication, HPV specific communication, and health care provider recommendation for vaccination (Ps < .05). Findings have implications for the role of health care providers as advocates for mother-daughter sexual communication and HPV vaccination, especially among survivors of childhood cancer. PMID- 26668214 TI - Best Practices for Chemotherapy Administration in Pediatric Oncology: Quality and Safety Process Improvements (2015). AB - The administration of chemotherapy to children with cancer is a high-risk process that must be performed in a safe and consistent manner with high reliability. Clinical trials play a major role in the treatment of children with cancer; conformance to chemotherapy protocol requirements and accurate documentation in the medical record are critical. Inconsistencies in the administration and documentation of chemotherapy were identified as opportunities for errors to occur. A major process improvement was initiated to establish best practices for nurses who administer chemotherapy to children. An interdisciplinary team was formed to evaluate the current process and to develop best practices based on current evidence, protocol requirements, available resources, and safety requirements. The process improvement focused on the establishment of standardized and safe administration techniques, exact administration times, and consistent electronic documentation that could easily be retrieved in medical record audits. Quality improvement tools including SBAR (Situation, Background, Assessment, Recommendation), process mapping, PDSA (Plan, Do. Study, Act) cycles, and quality metrics were used with this process improvement. The team established best practices in chemotherapy administration to children that have proven to be safe and reliable. Follow-up data have demonstrated that the project was highly successful and improved accuracy, patient and nurse safety, and effectiveness of chemotherapy administration. PMID- 26668216 TI - Controversies Among the Hypertension Guidelines. AB - Hypertension affects 80 million people in the United States. It remains poorly controlled, with only 54% of diagnosed patients treated to blood pressure targets. Hypertension management is complex in part due to the volume of antihypertensive agents, variable patient needs and responses, and inconsistent design and outcomes from clinical trials. Therefore, trustworthy clinical practice guidelines have a key role in hypertension management. The United States experienced a 10-year gap in publication of hypertension guidelines, followed by multiple guideline publications in 2013. These guidelines led to more controversy than clarity, as there was discordance among them. This review summarizes the guidelines and clinical statements influencing the current debate in order to facilitate appropriate application. PMID- 26668217 TI - American Psychiatry Should Join the Call to Abolish Solitary Confinement. PMID- 26668215 TI - A Gene Expression Signature Associated with Overall Survival in Patients with Hepatocellular Carcinoma Suggests a New Treatment Strategy. AB - Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist. PMID- 26668218 TI - Cleburne and the Pursuit of Equal Protection for Individuals With Mental Disorders. PMID- 26668219 TI - Application and Utility of Psychodynamic Principles in Forensic Assessment. AB - Effective practice of forensic psychiatry is dependent on a clinical recognition and understanding of core psychodynamic principles and theory. Practice guidelines, rooted in the ethics-based imperative to strive for honesty and objectivity, demand that practitioners remain vigilant to the development of bias and appreciate interpersonal dynamics that may be re-enacted in the forensic setting. Although it is not feasible to maintain complete impartiality, especially when confronted with the nature of certain offenses, knowledge of both conscious and unconscious responses can bolster the intellectual integrity of the clinical assessment. The identification of defense mechanisms within both the evaluator and evaluee and attention to transference and countertransference are essential for an accurate conceptualization of an offender's psychological functioning, vulnerabilities, and risk of reoffense. In this article, we review psychodynamic concepts and their potential impact in the forensic setting and underscore interventions that may aid in the elucidation and management of these processes. PMID- 26668220 TI - Commentary: Coming Full Circle--Psychoanalysis, Psychodynamics, and Forensic Psychiatry. AB - Drs. Simopoulos and Cohen argue that knowledge of one's unconscious processes improves the forensic psychiatrist's capacity to manage complex forensic situations and to generate forensic formulations and opinions that are demonstrably more valid and reliable, much like competence in cultural assessment and formulation. In practice, the challenges posed by the application of these principles in forensic settings are far outweighed by the potential benefit. Forensic practice is informed by many specialties. Forensic psychiatrists do not have to complete full training in these disciplines to make use of the knowledge and perspectives they offer. The same may not be true of psychodynamic assessment and formulation. Although much can be learned from supervision, case seminars, conferences, and reading, such knowledge does little to foster awareness of one's unconscious processes that by definition operate outside awareness and thus contribute to the vitiating effect of bias. To date, the only method whereby psychiatrists can effectively come to appreciate their own unconscious processes in action is arguably through their own analysis conducted in the course of training in analysis or psychodynamic psychotherapy. PMID- 26668221 TI - Outpatient Psychiatrists' Practices for Requesting Prior Treatment Records. AB - Patients' treatment records often contain information critical to risk assessment. We sought to determine whether psychiatrists treating outpatients agree about the standard of care (SOC) for requesting records from a patient's past clinicians. This web-based survey invited psychiatrists to review a hypothetical outpatient clinical vignette and to indicate whether they would request a release of information (ROI) from the patient for treatment records from past clinicians. Respondents also described the community SOC for similar scenarios and what they would do if a patient refused the ROI. Data were collected from June 15 through June 19, 2012. Most psychiatrists would try to obtain treatment records from any therapist, psychiatrist, or primary care physician seen by the patient within the past year. Some would require the patient's consent to ROI as a prerequisite to treatment. Few respondents felt that obtaining records from several years ago would be necessary in a typical, moderate-risk outpatient case. In an average outpatient scenario, the SOC would be to request treatment records from the past year. Psychiatrists rely heavily on clinical judgment when determining whether to obtain medical records from other providers. PMID- 26668222 TI - Commentary: Bringing Order to Chaos--How Psychiatrists Know the Standard of Care. AB - In this commentary, we explore the clinical and educational implications of the study by Recupero and Harms on the standard of care (SOC) as it pertains to obtaining psychiatric outpatient clinical records of prior treatment. We discuss differences between the legal and clinical SOCs and make recommendations to incorporate risk management training and education about the medicolegal aspects of SOC in psychiatry residency curricula. PMID- 26668223 TI - A Proposed Algorithm for the Pharmacotherapy of Impulsive Aggression. AB - A rational algorithm for effective pharmacotherapy for impulsive aggression takes into account five factors: sufficiently defined and characterized aggressive behavior; availability of agents studied by trials of sufficient quality; risks, side effects, and contraindications; severity of aggressive outbursts; and co occurring mental and medical conditions. Clinicians in forensic and correctional treatment centers, indeed in any treatment setting, should be able to optimize their effectiveness in treating impulsive aggression by using methods that consider these five factors. PMID- 26668224 TI - Transporting Forensic Psychiatric Patients. AB - Patients in a forensic psychiatric facility often require escorted transport to medical facilities for investigations or treatments of physical health ailments. Transporting these patients presents significant safety and custody challenges because of the nature of patients housed in forensic psychiatric facilities. A significant proportion of these patients may be transfers from the Department of Corrections (DOC) under legal mandates for psychiatric evaluation and treatment better provided in a hospital setting, and most of them will return to the DOC. Although departments of correction have protocols for escorting these potentially dangerous individuals, it is unclear whether receiving psychiatric hospitals have established procedures for maintaining the safety of others and custody of these individuals during transportation outside the hospital facility. The literature is sparse on precautions to be observed when transporting dangerous forensic psychiatric patients, including those with high escape risk. In this article, we describe one forensic inpatient facility's procedure for determining the appropriate level needed to transport these individuals outside of the forensic facility. We also describe the risk assessment procedure for determining level of transport. These are quality improvement measures resulting from a critical review of an incident of escape from the forensic facility several years ago. PMID- 26668225 TI - Treatment of Depression in Voluntary Versus Mandated Physicians. AB - Few if any publications discuss the effectiveness of voluntary versus mandated treatment for impaired physicians. This retrospective case-control study compared the recovery rates of physicians whose treatment was mandated or coerced by either licensure boards or employers (mandated physicians) with the rates for physicians admitted voluntarily (voluntary physicians) to the Menninger Clinic's Professionals in Crisis program from 2009 through 2012. Beck Depression Inventory (BDI)-II scores served as the primary outcome measure. At the time of admission, voluntary physicians were more depressed, but the improvement rates in the voluntary and mandated groups did not differ significantly. In addition, the two groups differed neither in rates of return to the healthy range of BDI-II scores, nor in whether BDI-II scores had decreased by at least two standard deviations by the time of discharge. These findings suggest that state physician health programs can continue to mandate physicians into treatment despite concerns that mandatory treatment may be less efficacious than voluntary treatment. PMID- 26668226 TI - Mental Illness and Mental Health Defenses: Perceptions of the Criminal Bar. AB - As the number of state mental hospital beds declines, persons with persistent mental illness are increasingly encountered by those working in the legal system. Attorneys may have little experience in working with this population. This research involved a 32-item written survey of the 492 members of the criminal bar in South Carolina. Demographic variables were surveyed, and attorneys were asked to define two common terms describing mental illnesses (delusion and psychosis) and the legal criteria for verdicts of not guilty by reason of insanity and guilty but mentally ill. They were also asked to identify the most severe mental illness (schizophrenia). Attitudes about these verdicts and about working with defendants who are mentally ill were also surveyed. Results indicate that attorneys are fairly knowledgeable about mental illness, but not verdicts involving mental illness, particularly the verdict of guilty but mentally ill. Most attorneys prefer to work with clients who do not have mental illness. However, as they become more experienced interacting with defendants who are affected by mental illness, they become more knowledgeable and are more willing to defend them. A large majority believe that their law school education about mental illness was inadequate. When comparing attorney occupations, public defenders were the most knowledgeable about mental illness and mental health defenses, followed by prosecutors and private defense attorneys. Judges were the least knowledgeable group. PMID- 26668227 TI - Hoarding, Housing, and DSM-5. AB - Hoarding of objects, trash, or animals has the potential to harm hoarders and others. Law enforcement and civil concerns arise, leading to situations ranging from health code violations to child abuse and potential eviction proceedings. DSM-5 included hoarding disorder among the obsessive-compulsive and related disorders. This change has created an opportunity for individuals who engage in severe hoarding to request reasonable accommodation from landlords, because their condition represents a disability under the Fair Housing and Americans with Disabilities Acts. We review the legal implications of hoarding disorder, tracking recent case law and arguments made in such disputes. PMID- 26668228 TI - Mild Traumatic Brain Injury Update: Forensic Neuropsychiatric Implications. AB - Traumatic brain injury (TBI) involves a wide range of potential neuropsychiatric outcomes, from death or profound impairment to full and fast recovery. This circumstance has contributed to an atmosphere with considerable potential for both clinical confusion and unjustified medicolegal outcomes. Given that mild (m)TBI accounts for most (~80%) TBI events and is generally associated with an excellent prognosis, the risk for erroneous clinical formulations and unmerited legal outcomes seems particularly high in cases involving mTBI. In this article, we summarize the recent results published by the International Collaboration on Mild Traumatic Brain Injury Prognosis (ICMTBIP) and the new approach of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, to TBI, and we explore the clinical and medicolegal implications. Symptoms that emerge after mTBI remain nonspecific, and potential etiologies are diverse. Clinicians and medicolegal experts should be familiar with the natural history of mTBI, able to recognize atypical outcomes, and willing to search for alternative explanations when confronted with persistent or severe impairment. PMID- 26668229 TI - Forensic Examinees Asking Probing Questions. PMID- 26668234 TI - Transcultural Nursing Scholars' Corner: Cultural Competence and Social Justice. PMID- 26668235 TI - 1,3-beta-D-Glucan contamination of common antimicrobials. AB - BACKGROUND: 1,3-beta-D-Glucan (BDG) is a fungal cell wall constituent used in the diagnosis of invasive fungal infections. BDG testing, although endorsed by the European Organization for Research and Treatment of Cancer, suffers from limited specificity. False-positive results have been linked to haemodialysis membranes, blood products, antineoplastic agents and antimicrobial use. OBJECTIVES: The aim of this study was to determine whether false-positive BDG results in the context of antimicrobial use are caused by BDG present in infusion solutions. METHODS: We obtained 35 antimicrobial drugs (30 antibiotics and 5 antifungals) and analysed their BDG content using two different assays. RESULTS: Twenty-five antimicrobials (20 antibiotics and all the tested antifungals) contained enough BDG to trigger a positive test. Depending on the substance, BDG varied between 9 and 2818 pg/mL. CONCLUSIONS: A majority of the available antimicrobial substances contained BDG, potentially limiting the utility of BDG testing in the context of prior exposure to these drugs. As the cumulative effects of repeated BDG exposure are unknown, efforts to reduce contamination should be considered. PMID- 26668237 TI - Has Psychiatric Medication Reduced Crime and Delinquency? AB - Several strands of research are consistent with the possibility that expansions in psychiatric medication usage have reduced crime and delinquency. Estimates suggest that medication usage has increased to as much as 9% of the youth population and up to 20% of the adult population in the United States and is high among populations associated with the criminal justice system. Studies show that four classes of commonly used psychiatric medication do reduce aggressive behavior, and crime rates are lower among diagnosed patients receiving such medications compared to those not. Prescriptions for medication increased fivefold for youth during the time that crime has declined in the United States and elsewhere, and two population-level analyses find some association between prescription rates and crime trends over time. However, true experimental studies are lacking, and one of the better trend studies does not show strong associations. This article proposes a research agenda for this issue. PMID- 26668231 TI - Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers. AB - Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers. In control toddlers, TBV variation significantly correlated with cell cycle and protein folding gene networks, potentially impacting neuron number and synapse development. In ASD toddlers, their correlations with brain size were lost as a result of considerable changes in network organization, while cell adhesion gene networks significantly correlated with TBV variation. Cell cycle networks detected in blood are highly preserved in the human brain and are upregulated during prenatal states of development. Overall, alterations were more pronounced in bigger brains. We identified 23 candidate genes for brain maldevelopment linked to 32 genes frequently mutated in ASD. The integrated network includes genes that are dysregulated in leukocyte and/or postmortem brain tissue of ASD subjects and belong to signaling pathways regulating cell cycle G1/S and G2/M phase transition. Finally, analyses of the CHD8 subnetwork and altered transcript levels from an independent study of CHD8 suppression further confirmed the central role of genes regulating neurogenesis and cell adhesion processes in ASD brain maldevelopment. PMID- 26668236 TI - Effects of fluconazole on the metabolomic profile of Candida albicans. AB - BACKGROUND: Little is known about the effects of fluconazole on the metabolism of Candida albicans. We performed LC/MS-based metabolomic profiling of the response of C. albicans cells to increasing doses of fluconazole. METHODS: C. albicans cells were cultured to mid-logarithmic growth phase in liquid medium and then inoculated in replicate on to nitrocellulose filters under vacuum filtration. Organisms were cultured to mid-logarithmic growth phase and treated with 0-4 mg/L fluconazole. Following metabolic quenching at mid-logarithmic growth phase, intracellular metabolites were extracted and analysed by LC/MS. Changes in pool sizes of individual metabolites were verified by Student's t-test, adjusted for multiple hypothesis testing by Benjamini-Hochberg correction. Distribution of metabolites was analysed by the Kyoto Encyclopedia of Genes and Genomes metabolic pathways database. RESULTS: We reproducibly detected 64 metabolites whose identities were confirmed by comparison against a pure standard and a library of accurate mass-retention time pairs. These 64 metabolites were broadly representative of eukaryotic central metabolic pathways. Among them 12 had their mean abundance significantly altered in response to increasing fluconazole concentrations. Pool sizes of four intermediates of central carbon metabolism (alpha-ketoglutarate, glucose-6-phosphate, phenylpyruvate and ribose-5-phosphate) and mevalonate were increased by 0.5-1.5-fold (P <= 0.05). Five amino acids (glycine, proline, tryptophan, aminoisobutanoate and asparagine) and guanine were decreased by 0.5-0.75-fold (P <= 0.05). CONCLUSIONS: Fluconazole treatment of C. albicans resulted in increased central carbon and decreased amino acid synthesis intermediates, suggesting a rerouting of metabolic pathways. The function of these metabolomic changes remains to be elucidated; however, they may represent previously unrecognized mechanisms of metabolic injury induced by fluconazole against C. albicans. PMID- 26668238 TI - A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory. AB - Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4 methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ~14%, ~34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey. PMID- 26668239 TI - Original footage of the Chilean miners with manganism published in Neurology in 1967. AB - Manganism has captured the imagination of neurologists for more than a century because of its similarities to Parkinson disease and its indirect but seminal role in the "l-dopa miracle." We present unpublished footage of the original case series reported in Neurology(r) in 1967 by Mena and Cotzias depicting the typical neurologic signs of manganism in 4 Chilean miners and their response to high doses of l-dopa. PMID- 26668240 TI - Complex periodic limb movements during sleep or partial epileptic seizures? PMID- 26668241 TI - Teaching NeuroImages: Neurocutaneous melanosis. PMID- 26668242 TI - Description and clinical application of the Pulfrich effect. PMID- 26668243 TI - Clinical Reasoning: A 50-year-old man with headache and cognitive decline. PMID- 26668244 TI - Journal Club: Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. PMID- 26668245 TI - Pearls & Oy-sters: Hemicrania epileptica: Unfolding the mystery of an unremitting migraine. PMID- 26668248 TI - Decision-making in job attendance within health care--a qualitative study. AB - BACKGROUND: Musculoskeletal complaints are considered a major cause of sickness absence, particularly in areas such as the health sector. However, little is known about the personal decision-making process for self-certified sickness absence. AIMS: To explore female health care workers' thoughts and experiences about work attendance when experiencing musculoskeletal symptoms. METHODS: A qualitative study using individual, semi-structured, in-depth interviews with eight female health care workers was performed. Questions were related to factors influencing the decision to attend work and decision-making when facing the dilemma of attending work when experiencing musculoskeletal symptoms. The data were analysed according to the systematic text condensation. RESULTS: Subjects reported a high threshold before calling in sick. Self-certified sickness absence was not a strategy for coping with musculoskeletal symptoms as participants chose to be physically active and work part-time rather than taking sickness absence. Making decisions about attending work fostered conflicting norms, as women faced a dilemma between feeling guilt towards colleagues and patients and taking care of their own health. CONCLUSIONS: The findings highlight the complexity of managing work when experiencing musculoskeletal symptoms, and the dilemmas faced by those affected. The importance of work environment factors and the fact that some women feel compelled to work part-time in order to prioritize their own health require further consideration. PMID- 26668247 TI - Patient-reported factors influencing return to work after joint replacement. AB - BACKGROUND: An increasing number of patients in the working population are undergoing total hip and knee replacement for osteoarthritis and the timing and success of return to work (RTW) is becoming increasingly important as a measure of success for these patients. There is limited understanding of the patient variables that determine the ability to RTW. AIMS: To explore the factors influencing RTW following hip and knee replacement from the patient's perspective. METHODS: A cross-sectional population-based postal survey carried out with patients of working age after hip and knee replacement surgery in a UK teaching hospital. Free text comments were collected regarding the experiences of patients returning to work following hip and knee replacement. Qualitative thematic analysis was undertaken to identify the factors influencing RTW from the patient's perspective. RESULTS: From the patients' perspective three key factors were identified that influenced RTW. Patients reported an improved physical and psychological performance at work after surgery in comparison to pre-operative functioning, although there was a lack of informed advice regarding RTW after surgery. Workplace support and adaptation of the job role enhanced the experience of RTW. CONCLUSIONS: Return to work is influenced by a combination of patient, clinician and occupational factors. The relationship between each of these needs to be explored in greater depth through further qualitative work to gain a wider understanding of the variables influencing patients' RTW following hip and knee replacement. PMID- 26668249 TI - Identifying British Army infantry recruit population characteristics using biographical data. AB - BACKGROUND: The infantry accounts for more than a quarter of the British Army but there is a lack of data about the social and educational background of its recruits. AIMS: To provide an insight into British Army infantry recruits' personal, social and educational background prior to enlistment. METHODS: The study sample consisted of infantry recruits who enlisted into the British Army School of Infantry. Each recruit completed a 95-item biographical questionnaire. Descriptive statistics were used to describe the sample in terms of demographic, physical, personal, social and educational attributes. RESULTS: The study sample consisted of 1000 male recruits. Over half of the recruits were consuming alcohol at a hazardous or harmful level prior to enlistment and 60% of recruits had used cannabis prior to joining the Army. Academic attainment was low, with the majority of recruits achieving GCSE grade C and below in most subjects, with 15% not taking any examinations. Over half the recruits had been in trouble with the police and either been suspended or expelled from school. CONCLUSIONS: Substance misuse and poor behaviour are highly prevalent among recruits prior to enlistment. Taken alongside existing evidence that some of these problems are commonplace among personnel in regular service, the assumption that the British Army infantry is, in itself, a cause of these behaviours should be questioned. PMID- 26668250 TI - Frequency and Risk Factors for Associated Lymphomas in Patients With Lymphomatoid Papulosis. AB - BACKGROUND: Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL). PATIENTS AND METHODS: Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan Meier method. RESULTS: We observed 52 cases of lymphomas (cutaneous, n = 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5-7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01-1.08; p = .011) and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18-26.18; p = .001). CONCLUSION: Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice. IMPLICATIONS FOR PRACTICE: The management of lymphomatoid papulosis (LyP) is that of an indolent cutaneous lymphoma, based on its excellent prognosis. However, this good prognosis is altered if LyP is associated with lymphoma. Furthermore, risk factors for and frequency of this association remain unclear in the literature. The results presented here demonstrate a high rate of association between LyP and other lymphomas (41%) as well as a long median delay of occurrence (5 years), which emphasizes the need for prolonged follow-up of patients with LyP. Moreover, two main risk factors (i.e., older age and presence of a T-cell clone in LyP lesions) are highlighted, which should help clinical practitioners to identify patients who require close management. PMID- 26668251 TI - A Phase III Study of Balugrastim Versus Pegfilgrastim in Breast Cancer Patients Receiving Chemotherapy With Doxorubicin and Docetaxel. AB - OBJECTIVES: This study aimed to evaluate the efficacy and safety of once-per cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy. METHODS: Breast cancer patients (n = 256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ~24 hours after chemotherapy (60 mg/m(2) doxorubicin and 75 mg/m(2) docetaxel, every 21 days for up to 4 cycles). The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2-4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1-4). Safety, pharmacokinetics, and immunogenicity were assessed. RESULTS: Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim, 1.3 with 50 mg of balugrastim, and 1.2 with pegfilgrastim (upper limit of 95% confidence intervals for between-group DSN differences was <1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50 mg of balugrastim, 2.1; pegfilgrastim, 2.6). Median terminal elimination half-life was ~37 hours for 40 mg of balugrastim, ~36 for 50 mg of balugrastim, and ~45 for pegfilgrastim. Antibody response to balugrastim was low and transient, with no neutralizing effect. CONCLUSION: Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles. IMPLICATIONS FOR PRACTICE: This paper provides efficacy and safety data for a new, once-per-cycle granulocyte colony stimulating factor, balugrastim, for the prevention of chemotherapy-induced neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. In this phase III trial, balugrastim was shown to be not inferior to pegfilgrastim in the duration of severe neutropenia in cycle 1 of doxorubicin/docetaxel chemotherapy, and the safety profiles of the two agents were similar. Once-per-cycle balugrastim is a safe and effective alternative to pegfilgrastim for hematopoietic support in patients with breast cancer receiving myelosuppressive chemotherapy associated with a greater than 20% risk of developing febrile neutropenia. PMID- 26668252 TI - The Effect of Introducing the Spinal Instability Neoplastic Score in Routine Clinical Practice for Patients With Spinal Metastases. AB - BACKGROUND: Stable spinal metastases are effectively treated with radiotherapy, whereas unstable spinal metastases often need surgical fixation followed by radiotherapy for local control. The Spinal Instability Neoplastic Score (SINS) was developed as a tool to assess spinal neoplastic related instability with the goal of helping to guide referrals among oncology specialists. We compare the average degree of spinal instability between patients with spinal metastases referred for surgery or for radiotherapy and evaluate whether this difference changed after introduction of the SINS in clinical practice. METHODS: All patients with spinal metastases treated with palliative surgery or radiotherapy in the period 2009-2013 were identified in two spine centers. For all patients, the SINS was scored on pretreatment imaging. The SINS before and after introduction of the SINS in 2011 were compared within the surgical and radiotherapy group. Furthermore, the overall SINS was compared between the two groups. RESULTS: The overall SINS was significantly higher in the surgical group, with a mean SINS of 10.7 (median 11) versus 7.2 (median 8) for the radiotherapy group. The mean SINS decreased significantly for both groups after introduction of the SINS in clinical practice from 11.2 to 10.3 in the surgical group and from 8.4 to 7.2 in the radiotherapy group. CONCLUSION: The SINS differed significantly between patients treated with surgery or radiotherapy. The introduction of SINS led to a decrease in SINS score for both groups, suggesting that using SINS in metastatic spinal disease increases awareness for instability and may subsequently result in earlier referrals for surgical intervention. IMPLICATIONS FOR PRACTICE: Spinal metastases can present with varying degrees of mechanical instability. Because unstable spinal metastases may respond insufficiently to palliative radiotherapy and can lead to loss of ambulation, timely detection and appropriate referral are important. The Spinal Instability Neoplastic Score (SINS) may help physicians caring for patients with metastasized disease to identify spinal instability before the onset of neurological deficits. In this study, it was shown that the introduction of SINS in routine practice led to a decrease in spinal instability in radiotherapy and surgical cohorts. The use of SINS may increase awareness of instability and subsequently result in earlier referrals. PMID- 26668253 TI - Breast Cancer Prevention: Can Women's Expectations Be Met? PMID- 26668255 TI - Annals of Pharmacotherapy Celebrating 50 Years: A Story That Keeps Getting Better! PMID- 26668256 TI - Corrigendum. PMID- 26668254 TI - Bringing Model-Based Prediction to Oncology Clinical Practice: A Review of Pharmacometrics Principles and Applications. AB - Despite much investment and progress, oncology is still an area with significant unmet medical needs, with new therapies and more effective use of current therapies needed. The emergent field of pharmacometrics combines principles from pharmacology (pharmacokinetics [PK] and pharmacodynamics [PD]), statistics, and computational modeling to support drug development and optimize the use of already marketed drugs. Although it has gained a role within drug development, its use in clinical practice remains scarce. The aim of the present study was to review the principal pharmacometric concepts and provide some examples of its use in oncology. Integrated population PK/PD/disease progression models as part of the pharmacometrics platform provide a powerful tool to predict outcomes so that the right dose can be given to the right patient to maximize drug efficacy and reduce drug toxicity. Population models often can be developed with routinely collected medical record data; therefore, we encourage the application of such models in the clinical setting by generating close collaborations between physicians and pharmacometricians. IMPLICATIONS FOR PRACTICE: The present review details how the emerging field of pharmacometrics can integrate medical record data with predictive pharmacological and statistical models of drug response to optimize and individualize therapies. In order to make this routine practice in the clinic, greater awareness of the potential benefits of the field is required among clinicians, together with closer collaboration between pharmacometricians and clinicians to ensure the requisite data are collected in a suitable format for pharmacometrics analysis. PMID- 26668258 TI - Deciding on coronary intervention: which lesion, which stent? PMID- 26668259 TI - European Commissioners petitioned for clean air and reduced noise pollution. PMID- 26668260 TI - Equine-Assisted Psychotherapy for adolescents experiencing depression and/or anxiety: A therapist's perspective. AB - Animal-Assisted Interventions (AAIs) are thought to overcome some of the limitations of traditional therapies as they do not rely exclusively on language as a medium for change. One such Animal-Assisted Therapy (AAT) approach involves horses as a therapeutic medium. Equine-Assisted Psychotherapy (EAP) comprises a collaborative effort between a licensed therapist and a horse professional working with clients to address treatment goals. The purpose of the present Australian-based qualitative study was to examine EAP facilitators' perspectives on the biospychosocial benefits and therapeutic outcomes of EAP for adolescents experiencing depression and/or anxiety. The findings suggest a range of improvements within adolescent clients, including increases in confidence, self esteem and assertiveness, as well as a decrease in undesirable behaviours. The effectiveness of the therapy was thought to be due to the experiential nature of involving horses in therapy. The lack of understanding in the wider community about EAP was seen as a barrier to recognition and acceptance of EAP as a valid therapeutic intervention. PMID- 26668261 TI - Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness. AB - Gram-negative bacteria express a number of sophisticated secretion systems to transport virulence factors across the cell envelope, including the type II secretion (T2S) system. Genes for the T2S components GspC through GspN and PilD are conserved among isolates of Acinetobacter baumannii, an increasingly common nosocomial pathogen that is developing multidrug resistance at an alarming rate. In contrast to most species, however, the T2S genes are dispersed throughout the genome rather than linked into one or two operons. Despite this unique genetic organization, we show here that the A. baumannii T2S system is functional. Deletion of gspD or gspE in A. baumannii ATCC 17978 results in loss of secretion of LipA, a lipase that breaks down long-chain fatty acids. Due to a lack of extracellular lipase, the gspD mutant, the gspE mutant, and a lipA deletion strain are incapable of growth on long-chain fatty acids as a sole source of carbon, while their growth characteristics are indistinguishable from those of the wild-type strain in nutrient-rich broth. Genetic inactivation of the T2S system and its substrate, LipA, also has a negative impact on in vivo fitness in a neutropenic murine model for bacteremia. Both the gspD and lipA mutants are outcompeted by the wild-type strain as judged by their reduced numbers in spleen and liver following intravenous coinoculation. Collectively, our findings suggest that the T2S system plays a hitherto-unrecognized role in in vivo survival of A. baumannii by transporting a lipase that may contribute to fatty acid metabolism. IMPORTANCE: Infections by multidrug-resistant Acinetobacter baumannii are a growing health concern worldwide, underscoring the need for a better understanding of the molecular mechanisms by which this pathogen causes disease. In this study, we demonstrated that A. baumannii expresses a functional type II secretion (T2S) system that is responsible for secretion of LipA, an extracellular lipase required for utilization of exogenously added lipids. The T2S system and the secreted lipase support in vivo colonization and thus contribute to the pathogenic potential of A. baumannii. PMID- 26668262 TI - Characterization of an Acinetobacter baumannii lptD Deletion Strain: Permeability Defects and Response to Inhibition of Lipopolysaccharide and Fatty Acid Biosynthesis. AB - Lipid A on the Gram-negative outer membrane (OM) is synthesized in the cytoplasm by the Lpx pathway and translocated to the OM by the Lpt pathway. Some Acinetobacter baumannii strains can tolerate the complete loss of lipopolysaccharide (LPS) resulting from the inactivation of early LPS pathway genes such as lpxC. Here, we characterized a mutant deleted for lptD, which encodes an OM protein that mediates the final translocation of fully synthesized LPS to the OM. Cells lacking lptD had a growth defect comparable to that of an lpxC deletion mutant under the growth conditions tested but were more sensitive to hydrophobic antibiotics, revealing a more significant impact on cell permeability from impaired LPS translocation than from the loss of LPS synthesis. Consistent with this, ATP leakage and N-phenyl-1-naphthylamine (NPN) fluorescence assays indicated a more severe impact of lptD deletion than of lpxC deletion on inner and outer membrane permeability, respectively. Targeted liquid chromatography-mass spectrometry (LCMS) analysis of LPS intermediates from UDP-3 O-R-3-hydroxylauroyl-N-acetyl-alpha-d-glucosamine through lipid IV(A) showed that the loss of LptD caused an accumulation of lipid IV(A). This suggested that pathway intermediate accumulation or mislocalization caused by the blockage of later LPS pathway steps impacts envelope integrity. Supporting this notion, chemical inhibition of lipid A precursor enzymes, including LpxC and FabB/F, in the lptD deletion strain partially rescued growth and permeability defects. IMPORTANCE: New antibiotics to treat Gram-negative bacterial infections are urgently needed. Inhibition of LPS biosynthesis is attractive because this would impact viability and cell permeability. Therefore, a better understanding of this pathway is important, especially in strains such as A. baumannii ATCC 19606, where LPS biosynthesis is not essential in vitro. We show that ATCC 19606 also survives the loss of the final translocation of LPS into the OM (lptD deletion). Intriguingly, this impaired cell envelope integrity more than the loss of LPS biosynthesis (lpxC deletion), presumably due to the accumulation of toxic intermediates. Supporting this, chemical inhibition of LPS biosynthesis partially reversed this permeability defect. This extends our understanding of the LPS machinery and provides insights into potential interrelationships of the target steps along this important pathway. PMID- 26668263 TI - Structural Similarities and Differences between Two Functionally Distinct SecA Proteins, Mycobacterium tuberculosis SecA1 and SecA2. AB - While SecA is the ATPase component of the major bacterial secretory (Sec) system, mycobacteria and some Gram-positive pathogens have a second paralog, SecA2. In bacteria with two SecA paralogs, each SecA is functionally distinct, and they cannot compensate for one another. Compared to SecA1, SecA2 exports a distinct and smaller set of substrates, some of which have roles in virulence. In the mycobacterial system, some SecA2-dependent substrates lack a signal peptide, while others contain a signal peptide but possess features in the mature protein that necessitate a role for SecA2 in their export. It is unclear how SecA2 functions in protein export, and one open question is whether SecA2 works with the canonical SecYEG channel to export proteins. In this study, we report the structure of Mycobacterium tuberculosis SecA2 (MtbSecA2), which is the first structure of any SecA2 protein. A high level of structural similarity is observed between SecA2 and SecA1. The major structural difference is the absence of the helical wing domain, which is likely to play a role in how MtbSecA2 recognizes its unique substrates. Importantly, structural features critical to the interaction between SecA1 and SecYEG are preserved in SecA2. Furthermore, suppressor mutations of a dominant-negative secA2 mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG or the translocating polypeptide substrate. These results support a model in which the mycobacterial SecA2 works with SecYEG. IMPORTANCE: SecA2 is a paralog of SecA1, which is the ATPase of the canonical bacterial Sec secretion system. SecA2 has a nonredundant function with SecA1, and SecA2 exports a distinct and smaller set of substrates than SecA1. This work reports the crystal structure of SecA2 of Mycobacterium tuberculosis (the first SecA2 structure reported for any organism). Many of the structural features of SecA1 are conserved in the SecA2 structure, including putative contacts with the SecYEG channel. Several structural differences are also identified that could relate to the unique function and selectivity of SecA2. Suppressor mutations of a secA2 mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG. PMID- 26668264 TI - Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations. AB - Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble alpha-glucan similar to amylopectin. Notably, this alternative form, termed "semi amylopectin," forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in Synechocystis sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of Synechocystis sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin producing strains. IMPORTANCE: This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates. PMID- 26668265 TI - Reexamining the Germination Phenotypes of Several Clostridium difficile Strains Suggests Another Role for the CspC Germinant Receptor. AB - Clostridium difficile spore germination is essential for colonization and disease. The signals that initiate C. difficile spore germination are a combination of taurocholic acid (a bile acid) and glycine. Interestingly, the chenodeoxycholic acid class (CDCA) bile acids competitively inhibit taurocholic acid-mediated germination, suggesting that compounds that inhibit spore germination could be developed into drugs that prophylactically prevent C. difficile infection or reduce recurring disease. However, a recent report called into question the utility of such a strategy to prevent infection by describing C. difficile strains that germinated in the apparent absence of bile acids or germinated in the presence of the CDCA inhibitor. Because the mechanisms of C. difficile spore germination are beginning to be elucidated, the mechanism of germination in these particular strains could yield important information on how C. difficile spores initiate germination. Therefore, we quantified the interaction of these strains with taurocholic acid and CDCA, the rates of spore germination, the release of DPA from the spore core, and the abundance of the germinant receptor complex (CspC, CspB, and SleC). We found that strains previously observed to germinate in the absence of taurocholic acid correspond to more potent 50% effective concentrations (EC50 values; the concentrations that achieve a half-maximum germination rate) of the germinant and are still inhibited by CDCA, possibly explaining the previous observations. By comparing the germination kinetics and the abundance of proteins in the germinant receptor complex, we revised our original model for CspC-mediated activation of spore germination and propose that CspC may activate spore germination and then inhibit downstream processes. IMPORTANCE: Clostridium difficile forms metabolically dormant spores that persist in the health care environment. In susceptible hosts, C. difficile spores germinate in response to certain bile acids and glycine. Blocking germination by C. difficile spores is an attractive strategy to prevent the initiation of disease or to block recurring infection. However, certain C. difficile strains have been identified whose spores germinate in the absence of bile acids or are not blocked by known inhibitors of C. difficile spore germination (calling into question the utility of such strategies). Here, we further investigate these strains and reestablish that bile acid activators and inhibitors of germination affect these strains and use these data to suggest another role for the C. difficile bile acid germinant receptor. PMID- 26668266 TI - Pathogenicity Island Cross Talk Mediated by Recombination Directionality Factors Facilitates Excision from the Chromosome. AB - Pathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase-mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. In this study, we examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential for Vibrio cholerae host colonization: Vibrio pathogenicity island 1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1 and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1- and VPI-2-encoded integrases. We demonstrated that the RDFs Vibrio excision factor A (VefA) and VefB bind at the attachment sites (overlapping the int promoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition, V. cholerae RDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs. IMPORTANCE: Deciphering the mechanisms of pathogenicity island excision is necessary for understanding the evolution and spread of these elements to their nonpathogenic counterparts. Such mechanistic insight would assist in predicting the mobility of uncharacterized genetic elements. This study identified extensive RDF-mediated cross talk between two nonhomologous VPIs and demonstrated the dual functionality of RDF proteins: (i) inducing PAI excision and (ii) acting as transcriptional regulators. Findings from this study may be implicated in determining the mobilome contribution of other bacteria with multiple MIGEs. PMID- 26668267 TI - Stability of the GraA Antitoxin Depends on Growth Phase, ATP Level, and Global Regulator MexT. AB - Bacterial type II toxin-antitoxin systems consist of a potentially poisonous toxin and an antitoxin that inactivates the toxic protein by binding to it. Most of the toxins regulate stress survival, but their activation depends on the stability of the antitoxin that has to be degraded in order for the toxin to be able to attack its cellular targets. The degradation of antitoxins is usually rapid and carried out by ATP-dependent protease Lon or Clp, which is activated under stress conditions. The graTA system of Pseudomonas putida encodes the toxin GraT, which can affect the growth rate and stress tolerance of bacteria but is under most conditions inactivated by the unusually stable antitoxin GraA. Here, we aimed to describe the stability features of the antitoxin GraA by analyzing its degradation rate in total cell lysates of P. putida. We show that the degradation rate of GraA depends on the growth phase of bacteria being fastest in the transition from exponential to stationary phase. In accordance with this, higher ATP levels were shown to stabilize GraA. Differently from other antitoxins, the main cellular proteases Lon and Clp are not involved in GraA stability. Instead, GraA seems to be degraded through a unique pathway involving an endoprotease that cleaves the antitoxin into two unequal parts. We also identified the global transcriptional regulator MexT as a factor for destabilization of GraA, which indicates that the degradation of GraA may be induced by conditions similar to those that activate MexT. IMPORTANCE: Toxin antitoxin (TA) modules are widespread in bacterial chromosomes and have important roles in stress tolerance. As activation of a type II toxin is triggered by proteolytic degradation of the antitoxin, knowledge about the regulation of the antitoxin stability is critical for understanding the activation of a particular TA module. Here, we report on the unusual degradation pathway of the antitoxin GraA of the recently characterized GraTA system. While GraA is uncommonly stable in the exponential and late-stationary phases, its degradation increases in the transition phase. The degradation pathway of GraA involves neither Lon nor Clp, which usually targets antitoxins, but rather an unknown endoprotease and the global regulator MexT, suggesting a new type of regulation of antitoxin stability. PMID- 26668269 TI - 2015 Jack Kenney Award for Outstanding Service. PMID- 26668268 TI - Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. AB - The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. Melanoma cells resistant to the BRAF inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ reduces the viability of resistant melanoma cells, whereas overexpression of constitutively active YAP induces resistance. Moreover, inhibition of actin polymerization and actomyosin tension in melanoma cells suppresses both YAP/TAZ activation and PLX4032 resistance. Our siRNA library screening identifies actin dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent resistance pathway. These results suggest that inhibition of actin remodeling is a potential strategy to suppress resistance in BRAF inhibitor therapies. PMID- 26668270 TI - Classic Spotlight: Before They Were Biofilms. PMID- 26668273 TI - Where is family medicine heading? PMID- 26668275 TI - The importance of being different: Inaugural Dr Ian McWhinney Lecture. PMID- 26668277 TI - Losing touch? Refining the role of physical examination in family medicine. PMID- 26668278 TI - [Physician-assisted suicide is not a failure of palliative care]. PMID- 26668279 TI - Right tool for the job. PMID- 26668280 TI - Response. PMID- 26668281 TI - An EMR-driven talk. PMID- 26668282 TI - Blind to patient's income. PMID- 26668283 TI - [Correction]. PMID- 26668284 TI - Femoroacetabular impingement and osteoarthritis of the hip. AB - OBJECTIVE: To outline the clinical presentation, physical examination findings, diagnostic criteria, and management options of femoroacetabular impingement (FAI). SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the pathogenesis, diagnosis, treatment, and prognosis of FAI. MAIN MESSAGE: In recent years, FAI has been increasingly recognized as a potential precursor and an important contributor to hip pain in the adult population and idiopathic hip osteoarthritis later in life. Femoroacetabular impingement is a collection of bony morphologic abnormalities of the hip joint that result in abnormal contact during motion. Cam-type FAI relates to a non-spherical osseous prominence of the proximal femoral neck or head-neck junction. Pincer-type FAI relates to excessive acetabular coverage over the femoral head, which can occur owing to several morphologic variants. Patients with FAI present with chronic, deep, or aching anterior groin pain most commonly in the sitting position, or during or after activity. Patients might also experience occasional sharp pains during activity. A thorough history should be taken that includes incidence of trauma and exercise frequency. A physical examination should be performed that includes a full hip, low back, and abdominal examination to assess for alternate causes of anterior groin pain. Diagnosis of FAI should be confirmed with radiography. Femoroacetabular impingement can be managed conservatively with rest, modification of activities, medications, and physiotherapy, or it can be treated surgically. CONCLUSION: Femoroacetabular impingement is an important cause of anterior groin pain. Early recognition and intervention by the primary care provider might be critical to alleviating morbidity and preventing FAI progression. PMID- 26668286 TI - Pneumothorax after acupuncture. PMID- 26668285 TI - Atrial fibrillation and physical activity: Should we exercise caution? AB - OBJECTIVE: To review the evidence on the effects of various levels of physical activity (PA) on the incidence of atrial fibrillation (AF) in both the general population and in endurance athletes. DATA SOURCES: A PubMed search was done initially using the MeSH headings or text words (with the search-field descriptor TIAB [title and abstract]) atrial fibrillation and exercise or physical activity or athlet* or sport*, without additional filters. Conclusions regarding quality and strength of evidence were based on the GRADE (grading of recommendations, assessment, development, and evaluation) system. STUDY SELECTION: No interventional studies were available. Observational studies were therefore considered acceptable, and, although larger long-term prospective cohort studies were preferred, case-control or cross-sectional trials were also included in this review. SYNTHESIS: Available evidence suggests a dose-response association linking increased exercise levels with reduced incident AF in women. The same is true in men at low and moderate levels of exertional activity. In men only, high levels of PA are associated with increased risk of AF in most, but not all, studies. This risk is moderate, with a hazard ratio of 1.29 in one of the better studies. The risk of AF for most people who exercise regularly is lower than that of a matched sedentary population. CONCLUSION: Atrial fibrillation is probably less common as PA increases, with a demonstrable dose-response relationship. Exercise at any level should be promoted for its effect on physical well-being and mortality reduction. In men exercising at high levels, beneficial effects on AF might be lost and risk might exceed that of the sedentary population; however, the evidence is neither robust nor consistent. These men should be made aware of this modest increase in risk should they choose to continue to engage in high levels of PA. PMID- 26668287 TI - Cyclobenzaprine for acute back pain. PMID- 26668288 TI - Therapeutic approach to noncompliance in HIV care. PMID- 26668292 TI - CFPC welcomes its 2015-2016 President, Dr Jennifer Hall. PMID- 26668289 TI - The Faces of Family Medicine 2011-2015. PMID- 26668294 TI - [Will disruption lead to renewal?]. PMID- 26668298 TI - Evaluation and Referral of Children With Signs of Early Puberty. AB - Concerns about possible early pubertal development are a common cause for referral to pediatric medical subspecialists. Several recent studies have suggested that onset of breast and/or pubic hair development may be occurring earlier than in the past. Although there is a chance of finding pathology in girls with signs of puberty before 8 years of age and in boys before 9 years of age, the vast majority of these children with signs of apparent puberty have variations of normal growth and physical development and do not require laboratory testing, bone age radiographs, or intervention. The most common of these signs of early puberty are premature adrenarche (early onset of pubic hair and/or body odor), premature thelarche (nonprogressive breast development, usually occurring before 2 years of age), and lipomastia, in which girls have apparent breast development which, on careful palpation, is determined to be adipose tissue. Indicators that the signs of sexual maturation may represent true, central precocious puberty include progressive breast development over a 4- to 6-month period of observation or progressive penis and testicular enlargement, especially if accompanied by rapid linear growth. Children exhibiting these true indicators of early puberty need prompt evaluation by the appropriate pediatric medical subspecialist. Therapy with a gonadotropin-releasing hormone agonist may be indicated, as discussed in this report. PMID- 26668299 TI - Nonmedical Use of Prescription Drugs and Sexual Risk Behaviors. AB - BACKGROUND: Substance use is associated with sexual risk behaviors among youth, but little is known about whether nonmedical prescription drug use, an increasingly common behavior, is associated with sexual risk behaviors. METHODS: Data from the 2011 and 2013 national Youth Risk Behavior Surveys, cross-sectional surveys conducted among nationally representative samples of students in grades 9 to 12 were combined (n = 29,008) to examine the association between ever taking prescription drugs without a doctor's prescription and sexual risk behaviors (ever having sexual intercourse, current sexual activity, lifetime number of sexual partners, condom use, and alcohol or drug use before last sexual intercourse). Using logistic regression models (adjusted for sex, race/ethnicity, grade, ever injection drug use, and use of alcohol, marijuana, heroin, cocaine, methamphetamines, ecstasy, and inhalants), we estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). RESULTS: Nonmedical use of prescription drugs (NMUPD) was associated with ever having sexual intercourse (aPR 1.16 [95% CI 1.11-1.22]), being currently sexually active (1.26 [1.20 1.33]), having >= 4 lifetime sexual partners (1.45 [1.34-1.57]), drinking alcohol or using drugs before last sexual intercourse (1.32 [1.17-1.48]), and not using a condom at last sexual intercourse (1.14 [1.05-1.23]). As the frequency of NMUPD increased, the association between NMUPD and each of the sexual risk behaviors increased in strength, suggesting a dose-response relationship. CONCLUSIONS: NMUPD is associated with sexual behaviors that put high school students at risk for sexually transmitted infections. These findings can be used to inform clinical and school-based interventions developed to reduce drug use and sexually transmitted infections. PMID- 26668300 TI - Clinical Interventions to Promote Breastfeeding by Latinas: A Meta-analysis. AB - CONTEXT: Breastfeeding duration and exclusivity among Latinas fall below recommended levels, indicating a need for targeted interventions. The effectiveness of clinical breastfeeding interventions for Latinas remains unclear. OBJECTIVE: To systematically review the documented effectiveness of clinical breastfeeding interventions on any and exclusive breastfeeding among Latinas. DATA SOURCES: English-language publications in Medline, CINAHL, and Embase were searched through May 28, 2015. STUDY SELECTION: Fourteen prospective, controlled studies describing 17 interventions met inclusion criteria. DATA EXTRACTION: Extracted study characteristics include study design, population characteristics, intervention components, timing and intensity of delivery, provider type, control procedures, and outcome measures. RESULTS: Random-effects meta-analyses estimated risk differences (RDs) between breastfeeding mothers in intervention and control arms of each study and 95% prediction intervals (PIs) within which 95% of intervals cover the true value estimated by a future study. Interventions increased any breastfeeding at 1 to 3 and 4 to 6 months (RD 0.04 [95% PI -0.15 to 0.23] and 0.08 [-0.08 to 0.25], respectively) and exclusive breastfeeding at 1 to 3 and 4 to 6 months (0.04 [-0.09 to 0.18] and 0.01 [-0.01 to 0.02]). Funnel plot asymmetry suggested publication bias for initiation and 1- to 3-month any breastfeeding. Estimates were slightly larger among interventions with prenatal and postpartum components, 3 to 6 patient contacts, and delivery by an International Board Certified Lactation Consultant or lay provider. LIMITATIONS: The published evidence for Latinas is limited, and studies have varying methodologic rigor. CONCLUSIONS: Breastfeeding interventions targeting Latinas increased any and exclusive breastfeeding compared with usual care. PMID- 26668301 TI - Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology. AB - The mineralocorticoid receptor (MR) and its ligand aldosterone are the principal modulators of hormone-regulated renal sodium reabsorption. In addition to the kidney, there are several other cells and organs expressing MR, in which its activation mediates pathologic changes, indicating potential therapeutic applications of pharmacological MR antagonism. Steroidal MR antagonists have been used for decades to fight hypertension and more recently heart failure. New therapeutic indications are now arising, and nonsteroidal MR antagonists are currently under development. This review is focused on nonclassic MR targets in cardiac, vascular, renal, metabolic, ocular, and cutaneous diseases. The MR, associated with other risk factors, is involved in organ fibrosis, inflammation, oxidative stress, and aging; for example, in the kidney and heart MR mediates hormonal tissue-specific ion channel regulation. Genetic and epigenetic modifications of MR expression/activity that have been documented in hypertension may also present significant risk factors in other diseases and be susceptible to MR antagonism. Excess mineralocorticoid signaling, mediated by aldosterone or glucocorticoids binding, now appears deleterious in the progression of pathologies that may lead to end-stage organ failure and could therefore benefit from the repositioning of pharmacological MR antagonists. PMID- 26668303 TI - Impact of UGT2B17 gene deletion on the steroid profile of an athlete. AB - The measurement of the testosterone to epitestosterone ratio (T/E ratio) in urine is often used as a marker for testosterone administration in the doping control field. This study examines the frequencies of the different expression forms of the UGT2B17 gene, and assesses their effects on this marker in volunteer subjects. The sample for this descriptive study was composed of male and female athletes aged between 16 and 55 years old who practiced different sports disciplines. All participants underwent a sports-medical physical examination, and subsequently provided 10 urine samples consecutively over a period of 48 h. The dependent variable examined was T/E and the main independent variable was the UGT2B17 gene polymorphism. During 1 year, 1410 urine samples were obtained from 141 athletes. The frequencies of the three genotypes were as follows: wt homozygotes (ins/ins) 48.2% (n = 68), mutant homozygotes (del/del) 12.1% (n = 17), and heterozygotes (ins/del) 39.7% (n = 56). Genotype distributions varied significantly (P < 0.001) according to ethnicity, 80% of Asian subjects being homozygous for the gene deletion (del/del) compared to 6.9% of Caucasian subjects. A multivariate analysis adjusted for genotype, age, sex, and sports discipline revealed that athletes with the del/del polymorphism showed a significantly lower mean T/E than heterozygotes (ins/del). In contrast, homozygous athletes for the gene insertion (ins/ins) showed higher mean T/E ratios than heterozygotes (ins/del). UGT2B17 gene deletion has a strong influence on the T/E ratio in urine, which is the most efficient indicator of testosterone prohormone misuse. Others factors studied seem not to have such an impact. The genotyping of UGT2B17 is an important source of information for understanding steroid profiling in the doping control field; therefore it is suggested that it be included in the Athletes Biological Passport. PMID- 26668302 TI - Retention Study of Flavonoids Under Different Chromatographic Modes. AB - The goal of this study was to investigate the chromatographic behavior of selected flavonoids from their different subgroups (flavonols, flavanones, flavones and isoflavones) in hydrophilic interaction liquid chromatography (HILIC). Chromatographic measurements were made on two different HILIC columns: cross-linked DIOL (Luna HILIC) and zwitterionic sulfoalkylbetaine (SeQuant ZIC HILIC). Separation parameters such as the content of acetonitrile and pH of an eluent were studied. On the ZIC column, the retention factors of flavonoids increased with decreasing water content in the mobile phase. The increase in pH of the aqueous component mainly affects the polarity of the analytes. DIOL stationary phase shows more or less apparent dual retention mechanism, HILIC at the acetonitrile (ACN) content >=75% and reversed phase (RP) with lower content of organic modifier. In the presence of ammonium acetate in the mobile phase, the retention of flavonoids onto the DIOL column increases without change in the selectivity of the separations. The similar effect, but considerably smaller was observed for aglycones on the ZIC column. The retention of studied glycosides (hesperidin, rutin) decreases in the presence of salt in the mobile phase. The significantly higher mass spectrometry sensitivity was observed under HILIC conditions in comparison with the most often used RP LC due to much higher content of ACN in the mobile phase. Finally, under optimal chromatographic conditions, the method was validated and applied for the determination of flavonoids in chamomile (Matricaria chamomilla L.) infusion. PMID- 26668304 TI - Redundant ERF-VII Transcription Factors Bind to an Evolutionarily Conserved cis Motif to Regulate Hypoxia-Responsive Gene Expression in Arabidopsis. AB - The response of Arabidopsis thaliana to low-oxygen stress (hypoxia), such as during shoot submergence or root waterlogging, includes increasing the levels of ~50 hypoxia-responsive gene transcripts, many of which encode enzymes associated with anaerobic metabolism. Upregulation of over half of these mRNAs involves stabilization of five group VII ethylene response factor (ERF-VII) transcription factors, which are routinely degraded via the N-end rule pathway of proteolysis in an oxygen- and nitric oxide-dependent manner. Despite their importance, neither the quantitative contribution of individual ERF-VIIs nor the cis regulatory elements they govern are well understood. Here, using single- and double-null mutants, the constitutively synthesized ERF-VIIs RELATED TO APETALA2.2 (RAP2.2) and RAP2.12 are shown to act redundantly as principle activators of hypoxia-responsive genes; constitutively expressed RAP2.3 contributes to this redundancy, whereas the hypoxia-induced HYPOXIA RESPONSIVE ERF1 (HRE1) and HRE2 play minor roles. An evolutionarily conserved 12-bp cis regulatory motif that binds to and is sufficient for activation by RAP2.2 and RAP2.12 is identified through a comparative phylogenetic motif search, promoter dissection, yeast one-hybrid assays, and chromatin immunopurification. This motif, designated the hypoxia-responsive promoter element, is enriched in promoters of hypoxia-responsive genes in multiple species. PMID- 26668306 TI - The Nucleotides That Bind: Finding the Motif behind the Hypoxia Response. PMID- 26668305 TI - Repeated Whole-Genome Duplication, Karyotype Reshuffling, and Biased Retention of Stress-Responding Genes in Buckler Mustard. AB - Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the beta- and alpha-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges. PMID- 26668307 TI - Correction. PMID- 26668308 TI - Gain-of-Function Mutation W493R in the Epithelial Sodium Channel Allosterically Reconfigures Intersubunit Coupling. AB - Sodium absorption in epithelial cells is rate-limited by the epithelial sodium channel (ENaC) activity in lung, kidney, and the distal colon. Pathophysiological conditions, such as cystic fibrosis and Liddle syndrome, result from water electrolyte imbalance partly due to malfunction of ENaC regulation. Because the quaternary structure of ENaC is yet undetermined, the bases of pathologically linked mutations in ENaC subunits alpha, beta, and gamma are largely unknown. Here, we present a structural model of heterotetrameric ENaC alpha1betaalpha2gamma that is consistent with previous cross-linking results and site-directed mutagenesis experiments. By using this model, we show that the disease-causing mutation alphaW493R rewires structural dynamics of the intersubunit interfaces alpha1beta and alpha2gamma. Changes in dynamics can allosterically propagate to the channel gate. We demonstrate that cleavage of the gamma-subunit, which is critical for full channel activation, does not mediate activation of ENaC by alphaW493R. Our molecular dynamics simulations led us to identify a channel-activating electrostatic interaction between alpha2Arg-493 and gammaGlu-348 at the alpha2gamma interface. By neutralizing a sodium-binding acidic patch at the alpha1beta interface, we reduced ENaC activation of alphaW493R by more than 2-fold. By combining homology modeling, molecular dynamics, cysteine cross-linking, and voltage clamp experiments, we propose a dynamics-driven model for the gain-of-function in ENaC by alphaW493R. Our integrated computational and experimental approach advances our understanding of structure, dynamics, and function of ENaC in its disease-causing state. PMID- 26668309 TI - A Novel Naphthalimide Compound Restores p53 Function in Non-small Cell Lung Cancer by Reorganizing the Bak.Bcl-xl Complex and Triggering Transcriptional Regulation. AB - p53 inactivation is a hallmark in non-small-cell lung cancer (NSCLC). It is therefore highly desirable to develop tumor-specific treatment for NSCLC therapy by restoring p53 function. Herein, a novel naphthalimide compound, NA-17, was identified as a promising drug candidate in view of both its anticancer activity and mechanism of action. NA-17 exhibited strong anticancer activity on a broad range of cancer cell lines but showed low toxicity to normal cell lines, such as HL-7702 and WI-38. Moreover, NA-17 showed p53-dependent inhibition selectivity in different NSCLC cell lines due to the activation state of endogenous p53 in the background level. Further studies revealed that NA-17 caused cell cycle arrest at the G1 phase, changed cell size, and induced apoptosis and cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that targeted accumulation of phospho-p53 in mitochondria and nuclei induced by NA-17 resulted in activation of Bak and direct binding of phospho-p53 to the target DNA sequences, thereby evoking cell apoptosis and cell cycle arrest and eventually leading to irreversible cancer cell inhibition. This work provided new insights into the molecular interactions and anticancer mechanisms of phospho-p53 dependent naphthalimide compounds. PMID- 26668310 TI - Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. AB - Extracellular matrix (ECM) remodeling regulates angiogenesis. However, the precise mechanisms by which structural changes in ECM proteins contribute to angiogenesis are not fully understood. Integrins are molecules with the ability to detect compositional and structural changes within the ECM and integrate this information into a network of signaling circuits that coordinate context dependent cell behavior. The role of integrin alphavbeta3 in angiogenesis is complex, as evidence exists for both positive and negative functions. The precise downstream signaling events initiated by alphavbeta3 may depend on the molecular characteristics of its ligands. Here, we identified an RGD-containing cryptic collagen epitope that is generated in vivo. Surprisingly, rather than inhibiting alphavbeta3 signaling, this collagen epitope promoted alphavbeta3 activation and stimulated angiogenesis and inflammation. An antibody directed to this RGDKGE epitope but not other RGD collagen epitopes inhibited angiogenesis and inflammation in vivo. The selective ability of this RGD epitope to promote angiogenesis and inflammation depends in part on its flanking KGE motif. Interestingly, a subset of macrophages may represent a physiologically relevant source of this collagen epitope. Here, we define an endothelial cell mechano signaling pathway in which a cryptic collagen epitope activates alphavbeta3 leading to an Src and p38 MAPK-dependent cascade that leads to nuclear accumulation of Yes-associated protein (YAP) and stimulation of endothelial cell growth. Collectively, our findings not only provide evidence for a novel mechano signaling pathway, but also define a possible therapeutic strategy to control alphavbeta3 signaling by targeting a pro-angiogenic and inflammatory ligand of alphavbeta3 rather than the receptor itself. PMID- 26668311 TI - Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cdelta. AB - Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCdelta, we aimed to understand the role of PKCdelta in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF alpha, IL-1beta, and IFN-gamma. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCdelta and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCdelta, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. PMID- 26668312 TI - Retinoid X Receptor-selective Signaling in the Regulation of Akt/Protein Kinase B Isoform-specific Expression. AB - The differentiation and fusion of myoblasts into mature myotubes are complex processes responding to multiple signaling pathways. The function of Akt/PKB is critical for myogenesis, but less is clear as to the regulation of its isoform specific expression. Bexarotene is a drug already used clinically to treat cancer, and it has the ability to enhance the commitment of embryonic stem cells into skeletal muscle lineage. Whereas bexarotene regulates fundamental biological processes through retinoid X receptor (RXR)-mediated gene expression, molecular pathways underlying its positive effects on myogenesis remain unclear. In this study, we have examined the signaling pathways that transmit bexarotene action in the context of myoblast differentiation. We show that bexarotene promotes myoblast differentiation and fusion through the activation of RXR and the regulation of Akt/PKB isoform-specific expression. Interestingly, bexarotene signaling appears to correlate with residue-specific histone acetylation and is able to counteract the detrimental effects of cachectic factors on myogenic differentiation. We also signify an isoform-specific role for Akt/PKB in RXR selective signaling to promote and to retain myoblast differentiation. Taken together, our findings establish the viability of applying bexarotene in the prevention and treatment of muscle-wasting disorders, particularly given the lack of drugs that promote myogenic differentiation available for potential clinical applications. Furthermore, the model of bexarotene-enhanced myogenic differentiation will provide an important avenue to identify additional genetic targets and specific molecular interactions that we can study and apply for the development of potential therapeutics in muscle regeneration and repair. PMID- 26668313 TI - Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase. AB - The intracellular infections of Mycobacterium tuberculosis, which is the causative agent of tuberculosis, are regulated by many cyclic dinucleotide signaling. Rv2837c from M. tuberculosis is a soluble, stand-alone DHH-DHHA1 domain phosphodiesterase that down-regulates c-di-AMP through catalytic degradation and plays an important role in M. tuberculosis infections. Here, we report the crystal structure of Rv2837c (2.0 A), and its complex with hydrolysis intermediate 5'-pApA (2.35 A). Our structures indicate that both DHH and DHHA1 domains are essential for c-di-AMP degradation. Further structural analysis shows that Rv2837c does not distinguish adenine from guanine, which explains why Rv2837c hydrolyzes all linear dinucleotides with almost the same efficiency. We observed that Rv2837c degraded other c-di-NMPs at a lower rate than it did on c di-AMP. Nevertheless, our data also showed that Rv2837c significantly decreases concentrations of both c-di-AMP and c-di-GMP in vivo. Our results suggest that beside its major role in c-di-AMP degradation Rv2837c could also regulate c-di GMP signaling pathways in bacterial cell. PMID- 26668314 TI - The Cellular Apoptosis Susceptibility Protein (CAS) Promotes Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis and Cell Proliferation. AB - A signature event during the cell intrinsic apoptotic pathway is mitochondrial outer membrane permeabilization, leading to formation of the apoptosome, a caspase activation complex. The cellular apoptosis susceptibility protein (CAS) can facilitate apoptosome assembly by stimulating nucleotide exchange on Apaf-1 following binding of cytochrome c. We report here that CAS expression itself is up-regulated during tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, and knockdown of CAS renders cells resistant to TRAIL. We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase 8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. We identified a novel signaling pathway whereby caspase-8 engages a feedforward cascade that leads to CAS up regulation and amplifies the apoptotic signal. Furthermore, in silico analysis revealed that expression of CAS is up-regulated at both the mRNA and DNA levels in human breast tumors, consistent with its role in promoting cell proliferation. Overexpression of various oncogenes led to CAS up-regulation in non-transformed cells. Intriguingly, oncogene-induced CAS up-regulation also resulted in greater susceptibility to TRAIL-induced cell death, consistent with its proapoptotic function. These findings suggest that CAS plays contrasting roles in proliferation and apoptosis and that overexpression of CAS in tumors could serve as a potential biomarker to guide therapeutic choices. PMID- 26668316 TI - Insulin Is Required to Maintain Albumin Expression by Inhibiting Forkhead Box O1 Protein. AB - Diabetes is accompanied by dysregulation of glucose, lipid, and protein metabolism. In recent years, much effort has been spent on understanding how insulin regulates glucose and lipid metabolism, whereas the effect of insulin on protein metabolism has received less attention. In diabetes, hepatic production of serum albumin decreases, and it has been long established that insulin positively controls albumin gene expression. In this study, we used a genetic approach in mice to identify the mechanism by which insulin regulates albumin gene transcription. Albumin expression was decreased significantly in livers with insulin signaling disrupted by ablation of the insulin receptor or Akt. Concomitant deletion of Forkhead Box O1 (Foxo1) in these livers rescued the decreased albumin secretion. Furthermore, activation of Foxo1 in the liver is sufficient to suppress albumin expression. These results suggest that Foxo1 acts as a repressor of albumin expression. PMID- 26668315 TI - Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5'-Terminal Cap and Hairpin. AB - The MAPK-interacting kinases 1 and 2 (MNK1 and MNK2) are activated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) or p38 in response to cellular stress and extracellular stimuli that include growth factors, cytokines, and hormones. Modulation of MNK activity affects translation of mRNAs involved in the cell cycle, cancer progression, and cell survival. However, the mechanism by which MNK selectively affects translation of these mRNAs is not understood. MNK binds eukaryotic translation initiation factor 4G (eIF4G) and phosphorylates the cap-binding protein eIF4E. Using a cell-free translation system from rabbit reticulocytes programmed with mRNAs containing different 5'-ends, we show that an MNK inhibitor, CGP57380, affects translation of only those mRNAs that contain both a cap and a hairpin in the 5'-UTR. Similarly, a C-terminal fragment of human eIF4G-1, eIF4G(1357-1600), which prevents binding of MNK to intact eIF4G, reduces eIF4E phosphorylation and inhibits translation of only capped and hairpin containing mRNAs. Analysis of proteins bound to m(7)GTP-Sepharose reveals that both CGP and eIF4G(1357-1600) decrease binding of eIF4E to eIF4G. These data suggest that MNK stimulates translation only of mRNAs containing both a cap and 5'-terminal RNA duplex via eIF4E phosphorylation, thereby enhancing the coupled cap-binding and RNA-unwinding activities of eIF4F. PMID- 26668317 TI - TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions: EVIDENCE FOR DISTINCT BINDING MECHANISMS FOR DIFFERENT TspanC8 PROTEINS. AB - A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane metalloprotease that cleaves the extracellular regions from its transmembrane substrates. ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins in mammals, of which the TspanC8 subgroup (Tspan5, 10, 14, 15, 17, and 33) promote ADAM10 intracellular trafficking and enzymatic maturation. However, the interaction between TspanC8s and ADAM10 has only been demonstrated in overexpression systems and the interaction mechanism remains undefined. To address these issues, an antibody was developed to Tspan14, which was used to show co-immunoprecipitation of Tspan14 with ADAM10 in primary human cells. Chimeric Tspan14 constructs demonstrated that the large extracellular loop of Tspan14 mediated its co-immunoprecipitation with ADAM10, and promoted ADAM10 maturation and trafficking to the cell surface. Chimeric ADAM10 constructs showed that membrane-proximal stalk, cysteine-rich, and disintegrin domains of ADAM10 mediated its co-immunoprecipitation with Tspan14 and other TspanC8s. This TspanC8-interacting region was required for ADAM10 exit from the endoplasmic reticulum. Truncated ADAM10 constructs revealed differential TspanC8 binding requirements for the stalk, cysteine-rich, and disintegrin domains. Moreover, Tspan15 was the only TspanC8 to promote cleavage of the ADAM10 substrate N-cadherin, whereas Tspan14 was unique in reducing cleavage of the platelet collagen receptor GPVI. These findings suggest that ADAM10 may adopt distinct conformations in complex with different TspanC8s, which could impact on substrate selectivity. Furthermore, this study identifies regions of TspanC8s and ADAM10 for potential interaction-disrupting therapeutic targeting. PMID- 26668318 TI - A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5) Forms Catalytically Active Oligomers. AB - The metalloproteinase ADAMTS-5 (A disintegrin and metalloproteinase with thrombospondin motifs) degrades aggrecan, a proteoglycan essential for cartilage structure and function. ADAMTS-5 is the major aggrecanase in mouse cartilage, and is also likely to be the major aggrecanase in humans. ADAMTS-5 is a multidomain enzyme, but the function of the C-terminal ancillary domains is poorly understood. We show that mutant ADAMTS-5 lacking the catalytic domain, but with a full suite of ancillary domains inhibits wild type ADAMTS activity, in vitro and in vivo, in a dominant-negative manner. The data suggest that mutant ADAMTS-5 binds to wild type ADAMTS-5; thus we tested the hypothesis that ADAMTS-5 associates to form oligomers. Co-elution, competition, and in situ PLA experiments using full-length and truncated recombinant ADAMTS-5 confirmed that ADAMTS-5 molecules interact, and showed that the catalytic and disintegrin-like domains support these intermolecular interactions. Cross-linking experiments revealed that recombinant ADAMTS-5 formed large, reduction-sensitive oligomers with a nominal molecular mass of ~ 400 kDa. The oligomers were unimolecular and proteolytically active. ADAMTS-5 truncates comprising the disintegrin and/or catalytic domains were able to competitively block full-length ADAMTS-5-mediated aggrecan cleavage, measured by production of the G1-EGE(373) neoepitope. These results show that ADAMTS-5 oligomerization is required for full aggrecanase activity, and they provide evidence that blocking oligomerization inhibits ADAMTS 5 activity. The data identify the surface provided by the catalytic and disintegrin-like domains of ADAMTS-5 as a legitimate target for the design of aggrecanase inhibitors. PMID- 26668320 TI - Perturbation of Critical Prolines in Gloeobacter violaceus Ligand-gated Ion Channel (GLIC) Supports Conserved Gating Motions among Cys-loop Receptors. AB - Gloeobacter violaceus ligand-gated ion channel (GLIC) has served as a valuable structural and functional model for the eukaryotic Cys-loop receptor superfamily. In Cys-loop and other receptors, we have previously demonstrated the crucial roles played by several conserved prolines. Here we explore the role of prolines in the gating transitions of GLIC. As conventional substitutions at some positions resulted in nonfunctional proteins, we used in vivo non-canonical amino acid mutagenesis to determine the specific structural requirements at these sites. Receptors were expressed heterologously in Xenopus laevis oocytes, and whole-cell electrophysiology was used to monitor channel activity. Pro-119 in the Cys-loop, Pro-198 and Pro-203 in the M1 helix, and Pro-299 in the M4 helix were sensitive to substitution, and distinct roles in receptor activity were revealed for each. In the context of the available structural data for GLIC, the behaviors of Pro-119, Pro-203, and Pro-299 mutants are consistent with earlier proline mutagenesis work. However, the Pro-198 site displays a unique phenotype that gives evidence of the importance of the region surrounding this residue for the correct functioning of GLIC. PMID- 26668319 TI - Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs. AB - Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1beta (control) treatment increased NGF, brain derived neurotrophic factor (BDNF), and IL-1beta gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1beta treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF kappaB, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-kappaB signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-kappaB inhibition may both attenuate chronic pain and slow the degenerative progress in vivo. PMID- 26668321 TI - Suppressor of Cytokine Signaling-3 (SOCS-3) Induces Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Expression in Hepatic HepG2 Cell Line. AB - The suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway activated by proinflammatory cytokines, including the tumor necrosis factor-alpha (TNF-alpha). SOCS3 is also implicated in hypertriglyceridemia associated to insulin resistance. Proprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively correlated to insulin resistance and plasma very low density lipoprotein (VLDL) triglycerides concentrations. The present study aimed to investigate the possible role of TNF-alpha and JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells. TNF-alpha induced both SOCS3 and PCSK9 in a concentration-dependent manner. This effect was inhibited by transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway. Retroviral overexpression of SOCS3 in HepG2 cells (HepG2(SOCS3)) strongly inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter activity and mRNA stability. Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observed with siRNA anti-STAT3. In addition, HepG2(SOCS3) express higher mRNA levels of key enzymes involved in the de novo lipogenesis, such as fatty-acid synthase, stearoyl-CoA desaturase (SCD)-1, and apoB. These responses were associated with a significant increase of SCD-1 protein, activation of sterol regulatory element-binding protein-1c (SREBP 1), accumulation of cellular triglycerides, and secretion of apoB. HepG2(SOCS3) show lower phosphorylation levels of insulin receptor substrate 1 (IRS-1) Tyr(896) and Akt Ser(473) in response to insulin. Finally, insulin stimulation produced an additive effect with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA. In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated by proinflammatory cytokine TNF-alpha in a SOCS3-dependent manner. PMID- 26668322 TI - Protein Phosphatase 1c Associated with the Cardiac Sodium Calcium Exchanger 1 Regulates Its Activity by Dephosphorylating Serine 68-phosphorylated Phospholemman. AB - The sodium (Na(+))-calcium (Ca(2+)) exchanger 1 (NCX1) is an important regulator of intracellular Ca(2+) homeostasis. Serine 68-phosphorylated phospholemman (pSer 68-PLM) inhibits NCX1 activity. In the context of Na(+)/K(+)-ATPase (NKA) regulation, pSer-68-PLM is dephosphorylated by protein phosphatase 1 (PP1). PP1 also associates with NCX1; however, the molecular basis of this association is unknown. In this study, we aimed to analyze the mechanisms of PP1 targeting to the NCX1-pSer-68-PLM complex and hypothesized that a direct and functional NCX1 PP1 interaction is a prerequisite for pSer-68-PLM dephosphorylation. Using a variety of molecular techniques, we show that PP1 catalytic subunit (PP1c) co localized, co-fractionated, and co-immunoprecipitated with NCX1 in rat cardiomyocytes, left ventricle lysates, and HEK293 cells. Bioinformatic analysis, immunoprecipitations, mutagenesis, pulldown experiments, and peptide arrays constrained PP1c anchoring to the K(I/V)FF motif in the first Ca(2+) binding domain (CBD) 1 in NCX1. This binding site is also partially in agreement with the extended PP1-binding motif K(V/I)FF-X5-8Phi1Phi2-X8-9-R. The cytosolic loop of NCX1, containing the K(I/V)FF motif, had no effect on PP1 activity in an in vitro assay. Dephosphorylation of pSer-68-PLM in HEK293 cells was not observed when NCX1 was absent, when the K(I/V)FF motif was mutated, or when the PLM- and PP1c binding sites were separated (mimicking calpain cleavage of NCX1). Co-expression of PLM and NCX1 inhibited NCX1 current (both modes). Moreover, co-expression of PLM with NCX1(F407P) (mutated K(I/V)FF motif) resulted in the current being completely abolished. In conclusion, NCX1 is a substrate-specifying PP1c regulator protein, indirectly regulating NCX1 activity through pSer-68-PLM dephosphorylation. PMID- 26668323 TI - Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells. AB - Gene delivery into hCD34+ hematopoietic stem/progenitor cells (HSPCs) using human immunodeficiency virus, type 1-derived lentiviral vectors (LVs) has several promising therapeutic applications. Numerous clinical trials are currently underway. However, the efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist, such as fibronectin fragments or cationic compounds. Recently, we discovered Vectofusin 1, a new transduction enhancer, also called LAH4-A4, a short histidine-rich amphipathic peptide derived from the LAH4 family of DNA transfection agents. Vectofusin-1 enhances the infectivity of lentiviral and gamma-retroviral vectors pseudotyped with various envelope glycoproteins. In this study, we compared a family of Vectofusin-1 isomers and showed that Vectofusin-1 remains the lead peptide for HSPC transduction enhancement with LVs pseudotyped with vesicular stomatitis virus glycoproteins and also with modified gibbon ape leukemia virus glycoproteins. By comparing the capacity of numerous Vectofusin-1 variants to promote the modified gibbon ape leukemia virus glycoprotein-pseudotyped lentiviral vector infectivity of HSPCs, the lysine residues on the N-terminal extremity of Vectofusin-1, a hydrophilic angle of 140 degrees formed by the histidine residues in the Schiffer-Edmundson helical wheel representation, hydrophobic residues consisting of leucine were all found to be essential and helped to define a minimal active sequence. The data also show that the critical determinants necessary for lentiviral transduction enhancement are partially different from those necessary for efficient antibiotic or DNA transfection activity of LAH4 derivatives. In conclusion, these results help to decipher the action mechanism of Vectofusin-1 in the context of hCD34+ cell-based gene therapy. PMID- 26668324 TI - Structural Insights into the HIV-1 Minus-strand Strong-stop DNA. AB - An essential step of human immunodeficiency virus type 1 (HIV-1) reverse transcription is the first strand transfer that requires base pairing of the R region at the 3'-end of the genomic RNA with the complementary r region at the 3' end of minus-strand strong-stop DNA (ssDNA). HIV-1 nucleocapsid protein (NC) facilitates this annealing process. Determination of the ssDNA structure is needed to understand the molecular basis of NC-mediated genomic RNA-ssDNA annealing. For this purpose, we investigated ssDNA using structural probes (nucleases and potassium permanganate). This study is the first to determine the secondary structure of the full-length HIV-1 ssDNA in the absence or presence of NC. The probing data and phylogenetic analysis support the folding of ssDNA into three stem-loop structures and the presence of four high-affinity binding sites for NC. Our results support a model for the NC-mediated annealing process in which the preferential binding of NC to four sites triggers unfolding of the three-dimensional structure of ssDNA, thus facilitating interaction of the r sequence of ssDNA with the R sequence of the genomic RNA. In addition, using gel retardation assays and ssDNA mutants, we show that the NC-mediated annealing process does not rely on a single pathway (zipper intermediate or kissing complex). PMID- 26668325 TI - The Evolutionarily Conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), Domain Catalytic (TLDc) Domain Is Neuroprotective against Oxidative Stress. AB - Oxidative stress is a pathological feature of many neurological disorders; therefore, utilizing proteins that are protective against such cellular insults is a potentially valuable therapeutic approach. Oxidation resistance 1 (OXR1) has been shown previously to be critical for oxidative stress resistance in neuronal cells; deletion of this gene causes neurodegeneration in mice, yet conversely, overexpression of OXR1 is protective in cellular and mouse models of amyotrophic lateral sclerosis. However, the molecular mechanisms involved are unclear. OXR1 contains the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) domain, a motif present in a family of proteins including TBC1 domain family member 24 (TBC1D24), a protein mutated in a range of disorders characterized by seizures, hearing loss, and neurodegeneration. The TLDc domain is highly conserved across species, although the structure-function relationship is unknown. To understand the role of this domain in the stress response, we carried out systematic analysis of all mammalian TLDc domain-containing proteins, investigating their expression and neuroprotective properties in parallel. In addition, we performed a detailed structural and functional study of this domain in which we identified key residues required for its activity. Finally, we present a new mouse insertional mutant of Oxr1, confirming that specific disruption of the TLDc domain in vivo is sufficient to cause neurodegeneration. Our data demonstrate that the integrity of the TLDc domain is essential for conferring neuroprotection, an important step in understanding the functional significance of all TLDc domain-containing proteins in the cellular stress response and disease. PMID- 26668326 TI - Role of the C-terminal Extension of Formin 2 in Its Activation by Spire Protein and Processive Assembly of Actin Filaments. AB - Formin 2 (Fmn2), a member of the FMN family of formins, plays an important role in early development. This formin cooperates with profilin and Spire, a WASP homology domain 2 (WH2) repeat protein, to stimulate assembly of a dynamic cytoplasmic actin meshwork that facilitates translocation of the meiotic spindle in asymmetric division of mouse oocytes. The kinase-like non-catalytic domain (KIND) of Spire directly interacts with the C-terminal extension of the formin homology domain 2 (FH2) domain of Fmn2, called FSI. This direct interaction is required for the synergy between the two proteins in actin assembly. We have recently demonstrated how Spire, which caps barbed ends via its WH2 domains, activates Fmn2. Fmn2 by itself associates very poorly to filament barbed ends but is rapidly recruited to Spire-capped barbed ends via the KIND domain, and it subsequently displaces Spire from the barbed end to elicit rapid processive assembly from profilin.actin. Here, we address the mechanism by which Spire and Fmn2 compete at barbed ends and the role of FSI in orchestrating this competition as well as in the processivity of Fmn2. We have combined microcalorimetric, fluorescence, and hydrodynamic binding assays, as well as bulk solution and single filament measurements of actin assembly, to show that removal of FSI converts Fmn2 into a Capping Protein. This activity is mimicked by association of KIND to Fmn2. In addition, FSI binds actin at filament barbed ends as a weak capper and plays a role in displacing the WH2 domains of Spire from actin, thus allowing the association of actin-binding regions of FH2 to the barbed end. PMID- 26668327 TI - The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling. AB - Vascular endothelial (VE)-cadherin transfers intracellular signals contributing to vascular hemostasis. Signaling through VE-cadherin requires association and activity of different intracellular partners. Yes-associated protein (YAP)/TAZ transcriptional cofactors are important regulators of cell growth and organ size. We show that EPS8, a signaling adapter regulating actin dynamics, is a novel partner of VE-cadherin and is able to modulate YAP activity. By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14-3-3-YAP associates with the VE-cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity. PMID- 26668328 TI - Thirty years of search and capture: The complex simplicity of mitotic spindle assembly. AB - Cell division is enacted by a microtubule-based, self-assembling macromolecular machine known as the mitotic spindle. In 1986, Kirschner and Mitchison proposed that by undergoing dynamic cycles of growth and disassembly, microtubules search for chromosomes. Capture of microtubules by the kinetochores progressively connects chromosomes to the bipolar spindle. 30 years later, "search and capture" remains the cornerstone of spindle assembly. However, a variety of facilitating mechanisms such as regulation of microtubule dynamics by diffusible gradients, spatially selective motor activities, and adaptive changes in chromosome architecture have been discovered. We discuss how these mechanisms ensure that the spindle assembles rapidly and with a minimal number of errors. PMID- 26668329 TI - The microtubule catastrophe promoter Sentin delays stable kinetochore-microtubule attachment in oocytes. AB - The critical step in meiosis is to attach homologous chromosomes to the opposite poles. In mouse oocytes, stable microtubule end-on attachments to kinetochores are not established until hours after spindle assembly, and phosphorylation of kinetochore proteins by Aurora B/C is responsible for the delay. Here we demonstrated that microtubule ends are actively prevented from stable attachment to kinetochores until well after spindle formation in Drosophila melanogaster oocytes. We identified the microtubule catastrophe-promoting complex Sentin-EB1 as a major factor responsible for this delay. Without this activity, microtubule ends precociously form robust attachments to kinetochores in oocytes, leading to a high proportion of homologous kinetochores stably attached to the same pole. Therefore, regulation of microtubule ends provides an alternative novel mechanism to delay stable kinetochore-microtubule attachment in oocytes. PMID- 26668330 TI - Whole-proteome genetic analysis of dependencies in assembly of a vertebrate kinetochore. AB - Kinetochores orchestrate mitotic chromosome segregation. Here, we use quantitative mass spectrometry of mitotic chromosomes isolated from a comprehensive set of chicken DT40 mutants to examine the dependencies of 93 confirmed and putative kinetochore proteins for stable association with chromosomes. Clustering and network analysis reveal both known and unexpected aspects of coordinated behavior for members of kinetochore protein complexes. Surprisingly, CENP-T depends on CENP-N for chromosome localization. The Ndc80 complex exhibits robust correlations with all other complexes in a "core" kinetochore network. Ndc80 associated with CENP-T interacts with a cohort of Rod, zw10, and zwilch (RZZ)-interacting proteins that includes Spindly, Mad1, and CENP E. This complex may coordinate microtubule binding with checkpoint signaling. Ndc80 associated with CENP-C forms the KMN (Knl1, Mis12, Ndc80) network and may be the microtubule-binding "workhorse" of the kinetochore. Our data also suggest that CENP-O and CENP-R may regulate the size of the inner kinetochore without influencing the assembly of the outer kinetochore. PMID- 26668331 TI - A Defect in DNA Ligase4 Enhances the Frequency of TALEN-Mediated Targeted Mutagenesis in Rice. AB - We have established methods for site-directed mutagenesis via transcription activator-like effector nucleases (TALENs) in the endogenous rice (Oryza sativa) waxy gene and demonstrated stable inheritance of TALEN-induced somatic mutations to the progeny. To analyze the role of classical nonhomologous end joining (cNHEJ) and alternative nonhomologous end joining (altNHEJ) pathways in TALEN induced mutagenesis in plant cells, we investigated whether a lack of DNA Ligase4 (Lig4) affects the kinetics of TALEN-induced double-strand break repair in rice cells. Deep-sequencing analysis revealed that the frequency of all types of mutations, namely deletion, insertion, combination of insertion with deletion, and substitution, in lig4 null mutant calli was higher than that in a lig4 heterozygous mutant or the wild type. In addition, the ratio of large deletions (greater than 10 bp) and deletions repaired by microhomology-mediated end joining (MMEJ) to total deletion mutations in lig4 null mutant calli was higher than that in the lig4 heterozygous mutant or wild type. Furthermore, almost all insertions (2 bp or greater) were shown to be processed via copy and paste of one or more regions around the TALENs cleavage site and rejoined via MMEJ regardless of genetic background. Taken together, our findings indicate that the dysfunction of cNHEJ leads to a shift in the repair pathway from cNHEJ to altNHEJ or synthesis dependent strand annealing. PMID- 26668332 TI - Type B Heterotrimeric G Protein gamma-Subunit Regulates Auxin and ABA Signaling in Tomato. AB - Heterotrimeric G proteins composed of alpha, beta, and gamma subunits are central signal transducers mediating the cellular response to multiple stimuli in most eukaryotes. Ggamma subunits provide proper cellular localization and functional specificity to the heterotrimer complex. Plant Ggamma subunits, divided into three structurally distinct types, are more diverse than their animal counterparts. Type B Ggamma subunits, lacking a carboxyl-terminal isoprenylation motif, are found only in flowering plants. We present the functional characterization of type B Ggamma subunit (SlGGB1) in tomato (Solanum lycopersicum). We show that SlGGB1 is the most abundant Ggamma subunit in tomato and strongly interacts with the Gbeta subunit. Importantly, the green fluorescent protein-SlGGB1 fusion protein as well as the carboxyl-terminal yellow fluorescent protein-SlGGB1/amino-terminal yellow fluorescent protein-Gbeta heterodimer were localized in the plasma membrane, nucleus, and cytoplasm. RNA interference mediated silencing of SlGGB1 resulted in smaller seeds, higher number of lateral roots, and pointy fruits. The silenced lines were hypersensitive to exogenous auxin, while levels of endogenous auxins were lower or similar to those of the wild type. SlGGB1-silenced plants also showed strong hyposensitivity to abscisic acid (ABA) during seed germination but not in other related assays. Transcriptome analysis of the transgenic seeds revealed abnormal expression of genes involved in ABA sensing, signaling, and response. We conclude that the type B Ggamma subunit SlGGB1 mediates auxin and ABA signaling in tomato. PMID- 26668333 TI - The Vacuolar Manganese Transporter MTP8 Determines Tolerance to Iron Deficiency Induced Chlorosis in Arabidopsis. AB - Iron (Fe) deficiency is a widespread nutritional disorder on calcareous soils. To identify genes involved in the Fe deficiency response, Arabidopsis (Arabidopsis thaliana) transfer DNA insertion lines were screened on a high-pH medium with low Fe availability. This approach identified METAL TOLERANCE PROTEIN8 (MTP8), a member of the Cation Diffusion Facilitator family, as a critical determinant for the tolerance to Fe deficiency-induced chlorosis, also on soil substrate. Subcellular localization to the tonoplast, complementation of a manganese (Mn) sensitive Saccharomyces cerevisiae yeast strain, and Mn sensitivity of mtp8 knockout mutants characterized the protein as a vacuolar Mn transporter suitable to prevent plant cells from Mn toxicity. MTP8 expression was strongly induced on low-Fe as well as high-Mn medium, which were both strictly dependent on the transcription factor FIT, indicating that high-Mn stress induces Fe deficiency. mtp8 mutants were only hypersensitive to Fe deficiency when Mn was present in the medium, which further suggested an Mn-specific role of MTP8 during Fe limitation. Under those conditions, mtp8 mutants not only translocated more Mn to the shoot than did wild-type plants but suffered in particular from critically low Fe concentrations and, hence, Fe chlorosis, although the transcriptional Fe deficiency response was up-regulated more strongly in mtp8. The diminished uptake of Fe from Mn-containing low-Fe medium by mtp8 mutants was caused by an impaired ability to boost the ferric chelate reductase activity, which is an essential process in Fe acquisition. These findings provide a mechanistic explanation for the long-known interference of Mn in Fe nutrition and define the molecular processes by which plants alleviate this antagonism. PMID- 26668334 TI - Biallelic Gene Targeting in Rice. AB - Sequence-specific nucleases (SSNs) have been used successfully in homology directed repair (HDR)-mediated gene targeting (GT) in many organisms. However, break-induced GT in plants remains challenging due to inefficient delivery of HDR templates and SSNs into plant nuclei. In many plants, including rice, Agrobacterium-mediated transformation is the most practical means of transformation because this biotic transformation system can deliver longer and more intact DNA payloads with less incorporation of fragmented DNA compared with physical transformation systems such as polyethylene glycol, electroporation, or biolistics. Following infection with Agrobacterium, transfer of transfer DNA (T DNA) to the nucleus and its integration into the plant genome occur consecutively during cocultivation, thus timing the induction of DNA double-strand breaks (DSBs) on the target gene to coincide with the delivery of the HDR template is crucial. To synchronize DSB induction and delivery of the HDR template, we transformed a Cas9 expression construct and GT vector harboring the HDR template with guide RNAs (gRNAs) targeting the rice acetolactate synthase (ALS) gene either separately or sequentially into rice calli. When gRNAs targeting ALS were transcribed transiently from double-stranded T-DNA containing the HDR template, DSBs were induced in the ALS locus by the assembled Cas9/gRNA complex and homologous recombination was stimulated. Contrary to our expectations, there was no great difference in GT efficiency between Cas9-expressing and nonexpressing cells. However, when gRNA targeting DNA ligase 4 was transformed with Cas9 prior to the GT experiment, GT efficiency increased dramatically and more than one line exhibiting biallelic GT at the ALS locus was obtained. PMID- 26668336 TI - Editorial Commentary: A Collaborative Model for Endpoint Development: Advancing the Science of Antibacterial Drug Clinical Trials. PMID- 26668335 TI - Ultrastructure of the Epidermal Cell Wall and Cuticle of Tomato Fruit (Solanum lycopersicum L.) during Development. AB - The epidermis plays a pivotal role in plant development and interaction with the environment. However, it is still poorly understood, especially its outer epidermal wall: a singular wall covered by a cuticle. Changes in the cuticle and cell wall structures are important to fully understand their functions. In this work, an ultrastructure and immunocytochemical approach was taken to identify changes in the cuticle and the main components of the epidermal cell wall during tomato fruit development. A thin and uniform procuticle was already present before fruit set. During cell division, the inner side of the procuticle showed a globular structure with vesicle-like particles in the cell wall close to the cuticle. Transition between cell division and elongation was accompanied by a dramatic increase in cuticle thickness, which represented more than half of the outer epidermal wall, and the lamellate arrangement of the non-cutinized cell wall. Changes in this non-cutinized outer wall during development showed specific features not shared with other cell walls. The coordinated nature of the changes observed in the cuticle and the epidermal cell wall indicate a deep interaction between these two supramolecular structures. Hence, the cuticle should be interpreted within the context of the outer epidermal wall. PMID- 26668337 TI - Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. AB - One important component in determining the benefits and harms of medical interventions is the use of well-defined and reliable outcome assessments as endpoints in clinical trials. Improving endpoints can better define patient benefits, allowing more accurate assessment of drug efficacy and more informed benefit-vs-risk decisions; another potential plus is facilitating efficient trial design. Since our first report in 2012, 2 Foundation for the National Institutes of Health Biomarkers Consortium Project Teams have continued to develop outcome assessments for potential uses as endpoints in registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. In addition, the teams have initiated similar work in the indications of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. This report provides an update on progress to date in these 4 diseases. PMID- 26668338 TI - Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature. AB - BACKGROUND: Powassan virus (POWV) is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits Lyme disease. The prevalence of POWV among animal hosts and vectors has been increasing. We present 8 cases of POWV encephalitis from Massachusetts and New Hampshire in 2013-2015. METHODS: We abstracted clinical and epidemiological information for patients with POWV encephalitis diagnosed at 2 hospitals in Massachusetts from 2013 to 2015. We compared their brain imaging with those in published findings from Powassan and other viral encephalitides. RESULTS: The patients ranged in age from 21 to 82 years, were, for the most part, previously healthy, and presented with syndromes of fever, headache, and altered consciousness. Infections occurred from May to September and were often associated with known tick exposures. In all patients, cerebrospinal fluid analyses showed pleocytosis with elevated protein. In 7 of 8 patients, brain magnetic resonance imaging demonstrated deep foci of increased T2/fluid-attenuation inversion recovery signal intensity. CONCLUSIONS: We describe 8 cases of POWV encephalitis in Massachusetts and New Hampshire in 2013 2015. Prior to this, there had been only 2 cases of POWV encephalitis identified in Massachusetts. These cases may represent emergence of this virus in a region where its vector, I. scapularis, is known to be prevalent or may represent the emerging diagnosis of an underappreciated pathogen. We recommend testing for POWV in patients who present with encephalitis in the spring to fall in New England. PMID- 26668339 TI - Hospital Outbreak of Pulmonary and Cutaneous Zygomycosis due to Contaminated Linen Items From Substandard Laundry. AB - BACKGROUND: Healthcare laundry-related infection is rare, and pulmonary zygomycosis due to contaminated hospital linens has never been reported. METHODS: We reported an outbreak investigation of zygomycosis in a university-affiliated teaching hospital. Air samplers, sponge swabs and Replicate Organism Detection and Counting (RODAC) contact plates were used for environmental sampling. The fungal isolates from clinical and environmental samples were identified by morphology, MALDI-TOF MS, and ITS1-5.8S-ITS2 rRNA gene cluster sequencing. RESULTS: From 2 June 2015 to 18 July 2015, 6 immunosuppressed patients developed pulmonary (n = 4) and/or cutaneous (n = 3) infection by a spore-forming mold, Rhizopus microsporus, through direct inhalation and skin contact of contaminated linen items supplied by a designated laundry. Seventy (27.8%) of 252 freshly laundered clothing and 15 (3.4%) of 443 nonclothing laundered linen items (pillow case, bed sheet, draw sheet) were contaminated by R. microsporus, which was significantly higher than those from other hospital laundries (0%, n = 451; P < .001) supplying linen to hospitals with no cases of zygomycosis reported during the same period. The fungal isolates from patients and linens were phylogenetically related. In sum, 61% of environmental samples and 100% of air samples at the designated laundry were also positive for zygomycetes, suggesting heavy environmental contamination. RODAC contact plates revealed mean total viable bacteria counts of freshly laundered items (1028 +/- 611 CFU/100 cm(2)) far exceeded the "hygienically clean" standard of 20 CFU/100 cm(2) set by the US healthcare textile certification requirement. CONCLUSIONS: Suboptimal conditions of washing, drying, and storage contributed to the massive linen contamination and the outbreak of zygomycosis. PMID- 26668340 TI - CD4 Cell Counts at Antiretroviral Therapy Initiation in Botswana Have Been Increasing. PMID- 26668341 TI - Enterovirus Contamination in Pediatric Hospitals: A Neglected Part of the Hand Foot-Mouth Disease Transmission Chain in China? PMID- 26668342 TI - Reply to Okatch et al. PMID- 26668343 TI - Decision Making in a Data-Poor Environment: Management of Brain Metastases From Testicular and Extragonadal Germ Cell Tumors. AB - The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 32-year-old man with a history of a mixed germ cell tumor of the testis presented with acute-onset, right-sided weakness and numbness. His previous treatment included orchiectomy, which revealed a 5-cm tumor that was 95% yolk sac tumor and 5% embryonal carcinoma, and retroperitoneal lymph node dissection for clinical stage I disease in January 2010, which revealed no nodal metastases. Starting in June 2010, he was treated with four cycles of etoposide and cisplatin for pulmonary and thoracic lymph node metastases and a rising serum alpha-fetoprotein (AFP) level. He subsequently received four cycles of paclitaxel, ifosfamide, and cisplatin for relapse in the lungs and mediastinal nodes with a rising AFP level starting in January 2011. He reported having a 2-week history of intermittent headaches in December 2011, when he presented with acute-onset, right-sided weakness and numbness. Computed tomographs of the head was obtained and demonstrated a left parietal intracranial hemorrhage without midline shift or hydrocephalus. Brain magnetic resonance imaging (MRI) showed a complex, 4.5-cm mass consistent with a hemorrhagic metastasis. His serum AFP level was elevated at 47 ng/mL. The patient became progressively obtunded and underwent emergency surgical decompression and resection of the tumor. Histopathologic evaluation of the resected tissue showed metastatic germ cell tumor predominantly consisting of a yolk sac element (Fig 1). His AFP level declined rapidly after resection, and computed tomography of the chest, abdomen, and pelvis showed no evidence of metastatic disease. However, 2 weeks later, his AFP level rose again, and repeat MRI of the brain showed a 3 cm mass in the left mesial parietal lobe adjacent to the resection site. He started treatment with filgrastim to facilitate collection of circulating hematopoietic stem cells. Several days later, after apheresis, he received his first of two cycles of high-dose carboplatin 700 mg/m(2) on days -5, -4, and -3 and etoposide 750 mg/m(2) on days -5, -4, and -3. The patient had a complete response to high-dose chemotherapy and no major acute complications. His cancer remains in complete remission 3 years later without additional treatment. His three lines of chemotherapy left him with chronic peripheral neuropathy. PMID- 26668344 TI - Pregnancy and the Risk of Relapse in Patients Diagnosed With Hodgkin Lymphoma. AB - PURPOSE: Many patients and clinicians are worried that pregnancy after the diagnosis of Hodgkin lymphoma (HL) may increase the risk of relapse despite a lack of empirical evidence to support such concerns. We investigated if an association exists between pregnancy and relapse in women with a diagnosis of HL. MATERIALS AND METHODS: Using Swedish healthcare registers combined with medical records, we included 449 women who received a diagnosis of HL between 1992 and 2009 and who were age 18 to 40 years at diagnosis. Follow-up started 6 months after diagnosis, when the patients' condition was assumed to be in remission. Pregnancy-associated relapse was defined as a relapse during pregnancy or within 5 years after delivery. Hazard ratios (HRs) with 95% CIs were estimated by using the Cox proportional hazards model. RESULTS: Among the 449 women, 144 (32%) became pregnant during follow-up. Overall, 47 relapses were recorded, of which one was a pregnancy-associated relapse. The adjusted HR for the comparison of the pregnancy-associated relapse rate to the non-pregnancy-associated relapse rate was 0.29 (95% CI, 0.04 to 2.18). The expected number of relapses in women with a recent pregnancy, given that they would experience the same relapse rate as that of women without a recent pregnancy, was 3.76; the observed-to-expected ratio was 0.27 (95% exact CI, 0.01 to 1.51). CONCLUSION: We found no evidence that a pregnancy after diagnosis increases the relapse rate among women whose HL is in remission. Survivors of HL need to consider a range of factors when deciding about future reproduction. However, given the results of this study, the risk of pregnancy-associated relapse does not need to be considered. PMID- 26668345 TI - The Value of Considering Cost, and the Cost of Not Considering Value. PMID- 26668347 TI - Using Minimal Residual Disease to Improve Treatment Response Definitions and Hematopoietic Cell Transplantation Strategy in Acute Leukemia. PMID- 26668346 TI - Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. AB - PURPOSE: To evaluate the efficacy and safety of high-dose, hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: In this single-arm, phase II, multi-institutional study, 92 patients with biopsy-confirmed HCC or ICC, determined to be unresectable by multidisciplinary review, with a Child-Turcotte Pugh score (CTP) of A or B, ECOG performance status of 0 to 2, no extrahepatic disease, and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent. Sample size was calculated to demonstrate > 80% local control (LC) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria at 2 years for HCC patients, with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC. RESULTS: Eighty-three patients were evaluable: 44 with HCC, 37 with ICC, and two with mixed HCC/ICC. The CTP score was A for 79.5% of patients and B for 15.7%; 4.8% of patients had no cirrhosis. Prior treatment had been given to 31.8% of HCC patients and 61.5% of ICC patients. The median maximum dimension was 5.0 cm (range, 1.9 to 12.0 cm) for HCC patients and 6.0 cm (range, 2.2 to 10.9 cm) for ICC patients. Multiple tumors were present in 27.3% of HCC patients and in 12.8% of ICC patients. Tumor vascular thrombosis was present in 29.5% of HCC patients and in 28.2% of ICC patients. The median dose delivered to both HCC and ICC patients was 58.0 Gy. With a median follow-up among survivors of 19.5 months, the LC rate at 2 years was 94.8% for HCC and 94.1% for ICC. The overall survival rate at 2 years was 63.2% for HCC and 46.5% ICC. CONCLUSION: High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely, supporting ongoing phase III trials of radiation in HCC and ICC. PMID- 26668348 TI - Association of SLCO2B1 Genotypes With Time to Progression and Overall Survival in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer. AB - PURPOSE: To validate the association of three previously demonstrated SLCO2B1 germline variants with time to progression (TTP) in patients receiving androgen deprivation therapy (ADT), and to evaluate if the SLCO2B1 genetic variants impacted overall survival (OS) for prostate cancer (PC). PATIENTS AND METHODS: Three single nucleotide polymorphisms (SNPs), exonic SNP rs12422149 and intronic SNPs rs1789693 and rs1077858, were genotyped in an independent validation cohort of 616 patients with PC who were treated with ADT at the Dana-Farber Cancer Institute from 1996 to 2013. Multivariable Cox proportional hazards regression adjusting for known prognostic factors estimated the association of these genetic variants with TTP and OS in patients receiving ADT. The expression of SLCO2B1 was examined in prostatectomy samples, and the impact of SLCO2B1 expression level on DHEAS (dehydroepiandrosterone sulfate) uptake was evaluated in cell lines. RESULTS: The association between exonic SNP rs12422149 and TTP in patients treated with ADT was confirmed in univariable (P = .019) and multivariable analyses (adjusted hazard ratio, 1.31; 95% CI, 1.00 to 1.72 for GG v AA/AG; P = .049). Because OS had not been previously evaluated, we examined the association in the combined initial and validation cohorts (N = 1,094). The intronic SNP rs1077858 was associated with OS in both univariable (P = .009; Bonferroni's method adjusted P = .027) and multivariable analyses (adjusted hazard ratio, 1.35; 95% CI, 1.07 to 1.71 for GG v AA/AG; P = .012). SLCO2B1 expression in normal prostate tissue and in 22RV1 cells carrying the major allele of SNP rs1077858 was significantly lower than in cells carrying the risk allele. We show in vitro that SLCO2B1 expression levels correlated with DHEAS uptake by PC cells. CONCLUSION: The association of SNP rs1077858 with OS may be a result of differential SLCO2B1 expression and the consequent increased uptake of DHEAS and subsequent resistance to ADT, which, in turn, may contribute to decreased OS. PMID- 26668349 TI - Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission? AB - PURPOSE: Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, >= 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution. PATIENTS AND METHODS: We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive. RESULTS: Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups. CONCLUSION: The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments. PMID- 26668350 TI - Analysis of Impact of Post-Treatment Biopsies in Phase I Clinical Trials. AB - PURPOSE: The use of biopsy-derived pharmacodynamic biomarkers is increasing in early-phase clinical trials. It remains unknown whether drug development is accelerated or enhanced by their use. We examined the impact of biopsy-derived pharmacodynamic biomarkers on subsequent drug development through a comprehensive analysis of phase I oncology studies from 2003 to 2010 and subsequent publications citing the original trials. METHODS: We conducted a search to identify and examine publications of phase I oncology studies including the use of biopsy-derived pharmacodynamic biomarkers between 2003 and 2010. Characteristics of those studies were extracted and analyzed, along with outcomes from the biomarker data. We then compiled and reviewed publications of subsequent phase II and III trials citing the original phase I biomarker studies to determine the impact on drug development. RESULTS: We identified 4,840 phase I oncology publications between 2003 and 2010. Seventy-two studies included a biopsy-derived pharmacodynamic biomarker. The proportion of biomarker studies including nondiagnostic biopsies increased over time (P = .002). A minimum of 1,873 tumor biopsies were documented in the 72 studies, 12 of which reported a statistically significant biomarker result. Thirty-three percent of studies (n = 24) were referenced by subsequent publications specifically with regard to the biomarkers. Only five positive biomarker studies were cited subsequently, and maximum tolerated dose was used for subsequent drug development in all cases. CONCLUSION: Despite their increased use, the impact of biopsy-derived pharmacodynamic biomarkers in phase I oncology studies on subsequent drug development remains uncertain. No impact on subsequent dose or schedule was demonstrated. This issue requires further evaluation, given the risk and cost of such studies. PMID- 26668351 TI - Population Susceptibility to Insecticides and the Development of Resistance in Bactrocera cucurbitae (Diptera: Tephritidae). AB - Excessive insecticide applications are commonly used to manage Bactrocera cucurbitae Coquillett in China. Resistance status, resistance development trends, and patterns of cross-resistance to insecticides in B. cucurbitae were investigated. Among 21 populations from Hainan Island, two populations expressed high resistance to beta-cypermethrin; seven, eight, and ten populations expressed intermediate resistance to spinosad, avermectin, and beta-cypermethrin, respectively; four, six, one, five, and four populations expressed low resistance to spinosad, avermectin, trichlorfon, beta-cypermethrin, and fipronil, respectively; and the remaining populations exhibited either minor resistance or remained susceptible. Analysis of the development of resistance showed that resistance levels to spinosad and avermectin were readily developed at 40.68- and 18.42-fold, respectively, and a spinosad-resistant strain also showed relative positive cross-resistance to beta-cypermethrin and avermectin, but relative negative cross-resistance to trichlorfon and fipronil. These data represent the most extensive survey of insecticide resistance conducted in B. cucurbitae to date, and the level of insecticide resistance in populations should be considered when designing control measures and pest management strategies. PMID- 26668352 TI - Photo Quiz. A 59-Year-Old Man With Multiple Liver Lesions, Rash, and Uveitis. PMID- 26668354 TI - Target selection by natural and redesigned PUF proteins. AB - Pumilio/fem-3 mRNA binding factor (PUF) proteins bind RNA with sequence specificity and modularity, and have become exemplary scaffolds in the reengineering of new RNA specificities. Here, we report the in vivo RNA binding sites of wild-type (WT) and reengineered forms of the PUF protein Saccharomyces cerevisiae Puf2p across the transcriptome. Puf2p defines an ancient protein family present throughout fungi, with divergent and distinctive PUF RNA binding domains, RNA-recognition motifs (RRMs), and prion regions. We identify sites in RNA bound to Puf2p in vivo by using two forms of UV cross-linking followed by immunopurification. The protein specifically binds more than 1,000 mRNAs, which contain multiple iterations of UAAU-binding elements. Regions outside the PUF domain, including the RRM, enhance discrimination among targets. Compensatory mutants reveal that one Puf2p molecule binds one UAAU sequence, and align the protein with the RNA site. Based on this architecture, we redesign Puf2p to bind UAAG and identify the targets of this reengineered PUF in vivo. The mutant protein finds its target site in 1,800 RNAs and yields a novel RNA network with a dramatic redistribution of binding elements. The mutant protein exhibits even greater RNA specificity than wild type. The redesigned protein decreases the abundance of RNAs in its redesigned network. These results suggest that reengineering using the PUF scaffold redirects and can even enhance specificity in vivo. PMID- 26668355 TI - Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia: Contribution to classical conditioning. AB - Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are critical regulators of neuronal excitability, but less is known about their possible roles in synaptic plasticity and memory circuits. Here, we characterized the HCN gene organization, channel properties, distribution, and involvement in associative and nonassociative forms of learning in Aplysia californica. Aplysia has only one HCN gene, which codes for a channel that has many similarities to the mammalian HCN channel. The cloned acHCN gene was expressed in Xenopus oocytes, which displayed a hyperpolarization-induced inward current that was enhanced by cGMP as well as cAMP. Similarly to its homologs in other animals, acHCN is permeable to K(+) and Na(+) ions, and is selectively blocked by Cs(+) and ZD7288. We found that acHCN is predominantly expressed in inter- and motor neurons, including LFS siphon motor neurons, and therefore tested whether HCN channels are involved in simple forms of learning of the siphon-withdrawal reflex in a semiintact preparation. ZD7288 (100 MUM) significantly reduced an associative form of learning (classical conditioning) but had no effect on two nonassociative forms of learning (intermediate-term sensitization and unpaired training) or baseline responses. The HCN current is enhanced by nitric oxide (NO), which may explain the postsynaptic role of NO during conditioning. HCN current in turn enhances the NMDA-like current in the motor neurons, suggesting that HCN channels contribute to conditioning through this pathway. PMID- 26668356 TI - Initiation factor 2 stabilizes the ribosome in a semirotated conformation. AB - Intersubunit rotation and movement of the L1 stalk, a mobile domain of the large ribosomal subunit, have been shown to accompany the elongation cycle of translation. The initiation phase of protein synthesis is crucial for translational control of gene expression; however, in contrast to elongation, little is known about the conformational rearrangements of the ribosome during initiation. Bacterial initiation factors (IFs) 1, 2, and 3 mediate the binding of initiator tRNA and mRNA to the small ribosomal subunit to form the initiation complex, which subsequently associates with the large subunit by a poorly understood mechanism. Here, we use single-molecule FRET to monitor intersubunit rotation and the inward/outward movement of the L1 stalk of the large ribosomal subunit during the subunit-joining step of translation initiation. We show that, on subunit association, the ribosome adopts a distinct conformation in which the ribosomal subunits are in a semirotated orientation and the L1 stalk is positioned in a half-closed state. The formation of the semirotated intermediate requires the presence of an aminoacylated initiator, fMet-tRNA(fMet), and IF2 in the GTP-bound state. GTP hydrolysis by IF2 induces opening of the L1 stalk and the transition to the nonrotated conformation of the ribosome. Our results suggest that positioning subunits in a semirotated orientation facilitates subunit association and support a model in which L1 stalk movement is coupled to intersubunit rotation and/or IF2 binding. PMID- 26668357 TI - Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-kappaB and JNK activation. AB - The aggressive activated B cell-like subtype of diffuse large B-cell lymphoma is characterized by aberrant B-cell receptor (BCR) signaling and constitutive nuclear factor kappa-B (NF-kappaB) activation, which is required for tumor cell survival. BCR-induced NF-kappaB activation requires caspase recruitment domain containing protein 11 (CARD11), and CARD11 gain-of-function mutations are recurrently detected in human diffuse large B-cell lymphoma (DLBCL). To investigate the consequences of dysregulated CARD11 signaling in vivo, we generated mice that conditionally express the human DLBCL-derived CARD11(L225LI) mutant. Surprisingly, CARD11(L225LI) was sufficient to trigger aggressive B-cell lymphoproliferation, leading to early postnatal lethality. CARD11(L225LI) constitutively associated with B-cell CLL/lymphoma 10 (BCL10) and mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) to simultaneously activate the NF-kappaB and c-Jun N-terminal kinase (JNK) signaling cascades. Genetic deficiencies of either BCL10 or MALT1 completely rescued the phenotype, and pharmacological inhibition of JNK was, similar to NF-kappaB blockage, toxic to autonomously proliferating CARD11(L225LI)-expressing B cells. Moreover, constitutive JNK activity was observed in primary human activated B cell-like (ABC)-DLBCL specimens, and human ABC-DLBCL cells were also sensitive to JNK inhibitors. Thus, our results demonstrate that enforced activation of CARD11/BCL10/MALT1 signaling is sufficient to drive transformed B-cell expansion in vivo and identify the JNK pathway as a therapeutic target for ABC-DLBCL. PMID- 26668359 TI - Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals. AB - The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander-Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ~9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals. PMID- 26668358 TI - Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition. AB - Diacylglycerol lipases (DAGLalpha and DAGLbeta) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLalpha is a short half life protein, and the inactivation of DAGLs disrupts cannabinoid receptor dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network. PMID- 26668360 TI - Evolution of habitat depth in the Jurassic-Cretaceous ammonoids. PMID- 26668361 TI - Deciphering the Denisovans. PMID- 26668362 TI - High-energy resolution X-ray absorption and emission spectroscopy reveals insight into unique selectivity of La-based nanoparticles for CO2. AB - The lanthanum-based materials, due to their layered structure and f-electron configuration, are relevant for electrochemical application. Particularly, La2O2CO3 shows a prominent chemoresistive response to CO2. However, surprisingly less is known about its atomic and electronic structure and electrochemically significant sites and therefore, its structure-functions relationships have yet to be established. Here we determine the position of the different constituents within the unit cell of monoclinic La2O2CO3 and use this information to interpret in situ high-energy resolution fluorescence-detected (HERFD) X-ray absorption near-edge structure (XANES) and valence-to-core X-ray emission spectroscopy (vtc XES). Compared with La(OH)3 or previously known hexagonal La2O2CO3 structures, La in the monoclinic unit cell has a much lower number of neighboring oxygen atoms, which is manifested in the whiteline broadening in XANES spectra. Such a superior sensitivity to subtle changes is given by HERFD method, which is essential for in situ studying of the interaction with CO2. Here, we study La2O2CO3-based sensors in real operando conditions at 250 degrees C in the presence of oxygen and water vapors. We identify that the distribution of unoccupied La d-states and occupied O p- and La d-states changes during CO2 chemoresistive sensing of La2O2CO3. The correlation between these spectroscopic findings with electrical resistance measurements leads to a more comprehensive understanding of the selective adsorption at La site and may enable the design of new materials for CO2 electrochemical applications. PMID- 26668363 TI - Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment. AB - The outer segments of vertebrate rod photoreceptors are renewed every 10 d. Outer segment components are transported from the site of synthesis in the inner segment through the connecting cilium, followed by assembly of the highly ordered discs. Two models of assembly of discrete discs involving either successive fusion events between intracellular rhodopsin-bearing vesicles or the evagination of the plasma membrane followed by fusion of adjacent evaginations have been proposed. Here we use immuno-electron microscopy and electron tomography to show that rhodopsin is transported from the inner to the outer segment via the ciliary plasma membrane, subsequently forming successive evaginations that "zipper" up proximally, but at their leading edges are free to make junctions containing the protocadherin, PCDH21, with the inner segment plasma membrane. Given the physical dimensions of the evaginations, coupled with likely instability of the membrane cortex at the distal end of the connecting cilium, we propose that the evagination occurs via a process akin to blebbing and is not driven by actin polymerization. Disassembly of these junctions is accompanied by fusion of the leading edges of successive evaginations to form discrete discs. This fusion is topologically different to that mediated by the membrane fusion proteins, SNAREs, as initial fusion is between exoplasmic leaflets, and is accompanied by gain of the tetraspanin rim protein, peripherin. PMID- 26668364 TI - Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly. AB - The endosomal sorting complexes required for transport (ESCRT) machinery functions in HIV-1 budding, cytokinesis, multivesicular body biogenesis, and other pathways, in the course of which it interacts with concave membrane necks and bud rims. To test the role of membrane shape in regulating ESCRT assembly, we nanofabricated templates for invaginated supported lipid bilayers. The assembly of the core ESCRT-III subunit CHMP4B/Snf7 is preferentially nucleated in the resulting 100-nm-deep membrane concavities. ESCRT-II and CHMP6 accelerate CHMP4B assembly by increasing the concentration of nucleation seeds. Superresolution imaging was used to visualize CHMP4B/Snf7 concentration in a negatively curved annulus at the rim of the invagination. Although Snf7 assemblies nucleate slowly on flat membranes, outward growth onto the flat membrane is efficiently nucleated at invaginations. The nucleation behavior provides a biophysical explanation for the timing of ESCRT-III recruitment and membrane scission in HIV-1 budding. PMID- 26668365 TI - Origin and diversification of wings: Insights from a neopteran insect. AB - Winged insects underwent an unparalleled evolutionary radiation, but mechanisms underlying the origin and diversification of wings in basal insects are sparsely known compared with more derived holometabolous insects. In the neopteran species Oncopeltus fasciatus, we manipulated wing specification genes and used RNA-seq to obtain both functional and genomic perspectives. Combined with previous studies, our results suggest the following key steps in wing origin and diversification. First, a set of dorsally derived outgrowths evolved along a number of body segments including the first thoracic segment (T1). Homeotic genes were subsequently co-opted to suppress growth of some dorsal flaps in the thorax and abdomen. In T1 this suppression was accomplished by Sex combs reduced, that when experimentally removed, results in an ectopic T1 flap similar to prothoracic winglets present in fossil hemipteroids and other early insects. Global gene expression differences in ectopic T1 vs. T2/T3 wings suggest that the transition from flaps to wings required ventrally originating cells, homologous with those in ancestral arthropod gill flaps/epipods, to migrate dorsally and fuse with the dorsal flap tissue thereby bringing new functional gene networks; these presumably enabled the T2/T3 wing's increased size and functionality. Third, "fused" wings became both the wing blade and surrounding regions of the dorsal thorax cuticle, providing tissue for subsequent modifications including wing folding and the fit of folded wings. Finally, Ultrabithorax was co-opted to uncouple the morphology of T2 and T3 wings and to act as a general modifier of hindwings, which in turn governed the subsequent diversification of lineage specific wing forms. PMID- 26668366 TI - Recombination patterns in maize reveal limits to crossover homeostasis. AB - During meiotic recombination, double-strand breaks (DSBs) are formed in chromosomal DNA and then repaired as either crossovers (COs) or non-crossovers (NCOs). In most taxa, the number of DSBs vastly exceeds the number of COs. COs are required for generating genetic diversity in the progeny, as well as proper chromosome segregation. Their formation is tightly controlled so that there is at least one CO per pair of homologous chromosomes whereas the maximum number of COs per chromosome pair is fairly limited. One of the main mechanisms controlling the number of recombination events per meiosis is CO homeostasis, which maintains a stable CO number even when the DSB number is dramatically altered. The existence of CO homeostasis has been reported in several species, including mouse, yeast, and Caenorhabditis elegans. However, it is not known whether homeostasis exists in the same form in all species. In addition, the studies of homeostasis have been conducted using mutants and/or transgenic lines exhibiting fairly severe meiotic phenotypes, and it is unclear how important homeostasis is under normal physiological conditions. We found that, in maize, CO control is robust only to ensure one CO per chromosome pair. However, once this limit is reached, the CO number is linearly related to the DSB number. We propose that CO control is a multifaceted process whose different aspects have a varying degree of importance in different species. PMID- 26668368 TI - Changing recruitment capacity in global fish stocks. AB - Marine fish and invertebrates are shifting their regional and global distributions in response to climate change, but it is unclear whether their productivity is being affected as well. Here we tested for time-varying trends in biological productivity parameters across 262 fish stocks of 127 species in 39 large marine ecosystems and high-seas areas (hereafter LMEs). This global meta analysis revealed widespread changes in the relationship between spawning stock size and the production of juvenile offspring (recruitment), suggesting fundamental biological change in fish stock productivity at early life stages. Across regions, we estimate that average recruitment capacity has declined at a rate approximately equal to 3% of the historical maximum per decade. However, we observed large variability among stocks and regions; for example, highly negative trends in the North Atlantic contrast with more neutral patterns in the North Pacific. The extent of biological change in each LME was significantly related to observed changes in phytoplankton chlorophyll concentration and the intensity of historical overfishing in that ecosystem. We conclude that both environmental changes and chronic overfishing have already affected the productive capacity of many stocks at the recruitment stage of the life cycle. These results provide a baseline for ecosystem-based fisheries management and may help adjust expectations for future food production from the oceans. PMID- 26668367 TI - Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. AB - Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target. PMID- 26668370 TI - Networks of military alliances, wars, and international trade. AB - We investigate the role of networks of alliances in preventing (multilateral) interstate wars. We first show that, in the absence of international trade, no network of alliances is peaceful and stable. We then show that international trade induces peaceful and stable networks: Trade increases the density of alliances so that countries are less vulnerable to attack and also reduces countries' incentives to attack an ally. We present historical data on wars and trade showing that the dramatic drop in interstate wars since 1950 is paralleled by a densification and stabilization of trading relationships and alliances. Based on the model we also examine some specific relationships, finding that countries with high levels of trade with their allies are less likely to be involved in wars with any other countries (including allies and nonallies), and that an increase in trade between two countries correlates with a lower chance that they will go to war with each other. PMID- 26668371 TI - Profile of Jean-Laurent Casanova. PMID- 26668369 TI - Unveiling the crucial intermediates in androgen production. AB - Ablation of androgen production through surgery is one strategy against prostate cancer, with the current focus placed on pharmaceutical intervention to restrict androgen synthesis selectively, an endeavor that could benefit from the enhanced understanding of enzymatic mechanisms that derives from characterization of key reaction intermediates. The multifunctional cytochrome P450 17A1 (CYP17A1) first catalyzes the typical hydroxylation of its primary substrate, pregnenolone (PREG) and then also orchestrates a remarkable C17-C20 bond cleavage (lyase) reaction, converting the 17-hydroxypregnenolone initial product to dehydroepiandrosterone, a process representing the first committed step in the biosynthesis of androgens. Now, we report the capture and structural characterization of intermediates produced during this lyase step: an initial peroxo-anion intermediate, poised for nucleophilic attack on the C20 position by a substrate-associated H-bond, and the crucial ferric peroxo-hemiacetal intermediate that precedes carbon-carbon (C-C) bond cleavage. These studies provide a rare glimpse at the actual structural determinants of a chemical transformation that carries profound physiological consequences. PMID- 26668373 TI - Q&As with Sharon Hammes-Schiffer. PMID- 26668372 TI - Specific induction of endogenous viral restriction factors using CRISPR/Cas derived transcriptional activators. AB - Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such "synergistic activation mediators" can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed. PMID- 26668374 TI - Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages. AB - Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement. PMID- 26668375 TI - Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation. AB - Phosphate (Pi) availability is a significant limiting factor for plant growth and productivity in both natural and agricultural systems. To cope with such limiting conditions, plants have evolved a myriad of developmental and biochemical strategies to enhance the efficiency of Pi acquisition and assimilation to avoid nutrient starvation. In the past decade, these responses have been studied in detail at the level of gene expression; however, the possible epigenetic components modulating plant Pi starvation responses have not been thoroughly investigated. Here, we report that an extensive remodeling of global DNA methylation occurs in Arabidopsis plants exposed to low Pi availability, and in many instances, this effect is related to changes in gene expression. Modifications in methylation patterns within genic regions were often associated with transcriptional activation or repression, revealing the important role of dynamic methylation changes in modulating the expression of genes in response to Pi starvation. Moreover, Arabidopsis mutants affected in DNA methylation showed that changes in DNA methylation patterns are required for the accurate regulation of a number of Pi-starvation-responsive genes and that DNA methylation is necessary to establish proper morphological and physiological phosphate starvation responses. PMID- 26668376 TI - Exogenous Hsp70 delays senescence and improves cognitive function in aging mice. AB - Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity. The potential of eHsp70 intranasal treatment to protect synaptic machinery in old animals offers a unique pharmacological approach for various neurodegenerative disorders associated with human aging. PMID- 26668378 TI - Reply to Douka et al.: Critical evaluation of the Ksar 'Akil chronologies. PMID- 26668379 TI - Statistical and archaeological errors invalidate the proposed chronology for the site of Ksar Akil. PMID- 26668377 TI - Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. AB - Changes of histone modification status at critical lineage-specifying gene loci in multipotent precursors can influence cell fate commitment. The contribution of these epigenetic mechanisms to natural killer (NK) cell lineage determination from common lymphoid precursors is not understood. Here we investigate the impact of histone methylation repressive marks (H3 Lys27 trimethylation; H3K27(me3)) on early NK cell differentiation. We demonstrate that selective loss of the histone lysine N-methyltransferase Ezh2 (enhancer of zeste homolog 2) or inhibition of its enzymatic activity with small molecules unexpectedly increased generation of the IL-15 receptor (IL-15R) CD122(+) NK precursors and mature NK progeny from both mouse and human hematopoietic stem and progenitor cells. Mechanistic studies revealed that enhanced NK cell expansion and cytotoxicity against tumor cells were associated with up-regulation of CD122 and the C-type lectin receptor NKG2D. Moreover, NKG2D deficiency diminished the positive effects of Ezh2 inhibitors on NK cell commitment. Identification of the contribution of Ezh2 to NK lineage specification and function reveals an epigenetic-based mechanism that regulates NK cell development and provides insight into the clinical application of Ezh2 inhibitors in NK-based cancer immunotherapies. PMID- 26668380 TI - Round-the-clock power supply and a sustainable economy via synergistic integration of solar thermal power and hydrogen processes. AB - We introduce a paradigm-"hydricity"-that involves the coproduction of hydrogen and electricity from solar thermal energy and their judicious use to enable a sustainable economy. We identify and implement synergistic integrations while improving each of the two individual processes. When the proposed integrated process is operated in a standalone, solely power production mode, the resulting solar water power cycle can generate electricity with unprecedented efficiencies of 40-46%. Similarly, in standalone hydrogen mode, pressurized hydrogen is produced at efficiencies approaching ~50%. In the coproduction mode, the coproduced hydrogen is stored for uninterrupted solar power production. When sunlight is unavailable, we envision that the stored hydrogen is used in a "turbine"-based hydrogen water power (H2WP) cycle with the calculated hydrogen-to electricity efficiency of 65-70%, which is comparable to the fuel cell efficiencies. The H2WP cycle uses much of the same equipment as the solar water power cycle, reducing capital outlays. The overall sun-to-electricity efficiency of the hydricity process, averaged over a 24-h cycle, is shown to approach ~35%, which is nearly the efficiency attained by using the best multijunction photovoltaic cells along with batteries. In comparison, our proposed process has the following advantages: (i) It stores energy thermochemically with a two- to threefold higher density, (ii) coproduced hydrogen has alternate uses in transportation/chemical/petrochemical industries, and (iii) unlike batteries, the stored energy does not discharge over time and the storage medium does not degrade with repeated uses. PMID- 26668382 TI - Dogs lap using acceleration-driven open pumping. AB - Dogs lap because they have incomplete cheeks and cannot suck. When lapping, a dog's tongue pulls a liquid column from the bath, suggesting that the hydrodynamics of column formation are critical to understanding how dogs drink. We measured lapping in 19 dogs and used the results to generate a physical model of the tongue's interaction with the air-fluid interface. These experiments help to explain how dogs exploit the fluid dynamics of the generated column. The results demonstrate that effects of acceleration govern lapping frequency, which suggests that dogs curl the tongue to create a larger liquid column. Comparing lapping in dogs and cats reveals that, despite similar morphology, these carnivores lap in different physical regimes: an unsteady inertial regime for dogs and steady inertial regime for cats. PMID- 26668383 TI - Correction for Zelezniak et al., Metabolic dependencies drive species co occurrence in diverse microbial communities. PMID- 26668381 TI - H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep wake regulatory neurons in mice. AB - An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption. PMID- 26668385 TI - Correction for Ishii et al., Nascent chain-monitored remodeling of the Sec machinery for salinity adaptation of marine bacteria. PMID- 26668384 TI - KCNE3 acts by promoting voltage sensor activation in KCNQ1. AB - KCNE beta-subunits assemble with and modulate the properties of voltage-gated K(+) channels. In the colon, stomach, and kidney, KCNE3 coassembles with the alpha-subunit KCNQ1 to form K(+) channels important for K(+) and Cl(-) secretion that appear to be voltage-independent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate. PMID- 26668386 TI - Polymer-supported CuPd nanoalloy as a synergistic catalyst for electrocatalytic reduction of carbon dioxide to methane. AB - Developing sustainable energy strategies based on CO2 reduction is an increasingly important issue given the world's continued reliance on hydrocarbon fuels and the rise in CO2 concentrations in the atmosphere. An important option is electrochemical or photoelectrochemical CO2 reduction to carbon fuels. We describe here an electrodeposition strategy for preparing highly dispersed, ultrafine metal nanoparticle catalysts on an electroactive polymeric film including nanoalloys of Cu and Pd. Compared with nanoCu catalysts, which are state-of-the-art catalysts for CO2 reduction to hydrocarbons, the bimetallic CuPd nanoalloy catalyst exhibits a greater than twofold enhancement in Faradaic efficiency for CO2 reduction to methane. The origin of the enhancement is suggested to arise from a synergistic reactivity interplay between Pd-H sites and Cu-CO sites during electrochemical CO2 reduction. The polymer substrate also appears to provide a basis for the local concentration of CO2 resulting in the enhancement of catalytic current densities by threefold. The procedure for preparation of the nanoalloy catalyst is straightforward and appears to be generally applicable to the preparation of catalytic electrodes for incorporation into electrolysis devices. PMID- 26668387 TI - Correction for Navarro et al., Airborne measurements of organic bromine compounds in the Pacific tropical tropopause layer. PMID- 26668388 TI - Correction to Supporting Information for Danielsson et al., Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model. PMID- 26668390 TI - The point of no return in vetoing self-initiated movements. AB - In humans, spontaneous movements are often preceded by early brain signals. One such signal is the readiness potential (RP) that gradually arises within the last second preceding a movement. An important question is whether people are able to cancel movements after the elicitation of such RPs, and if so until which point in time. Here, subjects played a game where they tried to press a button to earn points in a challenge with a brain-computer interface (BCI) that had been trained to detect their RPs in real time and to emit stop signals. Our data suggest that subjects can still veto a movement even after the onset of the RP. Cancellation of movements was possible if stop signals occurred earlier than 200 ms before movement onset, thus constituting a point of no return. PMID- 26668389 TI - Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. AB - A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1beta, and TNF-alpha) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. PMID- 26668391 TI - Human RNase L tunes gene expression by selectively destabilizing the microRNA regulated transcriptome. AB - Double-stranded RNA (dsRNA) activates the innate immune system of mammalian cells and triggers intracellular RNA decay by the pseudokinase and endoribonuclease RNase L. RNase L protects from pathogens and regulates cell growth and differentiation by destabilizing largely unknown mammalian RNA targets. We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and nontargets. We show that this RNase L-dependent decay selectively affects transcripts regulated by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these miRs and acts as a suppressor of proliferation and adhesion in mammalian cells. Our data suggest that RNase L-dependent decay serves to establish an antiproliferative state via destabilization of the miR-regulated transcriptome. PMID- 26668392 TI - Data contradict common perceptions about a controversial provision of the US Endangered Species Act. AB - Separating myth and reality is essential for evaluating the effectiveness of laws. Section 7 of the US Endangered Species Act (Act) directs federal agencies to help conserve threatened and endangered species, including by consulting with the US Fish and Wildlife Service (FWS) or National Marine Fisheries Service on actions the agencies authorize, fund, or carry out. Consultations ensure that actions do not violate the Act's prohibitions on "jeopardizing" listed species or "destroying or adversely modifying" these species' critical habitat. Because these prohibitions are broad, many people consider section 7 the primary tool for protecting species under the Act, whereas others believe section 7 severely impedes economic development. This decades-old controversy is driven primarily by the lack of data on implementation: past analyses are either over 25 y old or taxonomically restricted. We analyze data on all 88,290 consultations recorded by FWS from January 2008 through April 2015. In contrast to conventional wisdom about section 7 implementation, no project was stopped or extensively altered as a result of FWS finding jeopardy or adverse modification during this period. We also show that median consultation duration is far lower than the maximum allowed by the Act, and several factors drive variation in consultation duration. The results discredit many of the claims about the onerous nature of section 7 but also raise questions as to how federal agencies could apply this tool more effectively to conserve species. We build on the results to identify ways to improve the effectiveness of consultations for imperiled species conservation and increase the efficiency of consultations. PMID- 26668393 TI - Oscillatory phase shapes syllable perception. AB - The role of oscillatory phase for perceptual and cognitive processes is being increasingly acknowledged. To date, little is known about the direct role of phase in categorical perception. Here we show in two separate experiments that the identification of ambiguous syllables that can either be perceived as /da/ or /ga/ is biased by the underlying oscillatory phase as measured with EEG and sensory entrainment to rhythmic stimuli. The measured phase difference in which perception is biased toward /da/ or /ga/ exactly matched the different temporal onset delays in natural audiovisual speech between mouth movements and speech sounds, which last 80 ms longer for /ga/ than for /da/. These results indicate the functional relationship between prestimulus phase and syllable identification, and signify that the origin of this phase relationship could lie in exposure and subsequent learning of unique audiovisual temporal onset differences. PMID- 26668394 TI - Bovine NK-lysin: Copy number variation and functional diversification. AB - NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in ~30-35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer's patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants. PMID- 26668396 TI - Contact efflorescence as a pathway for crystallization of atmospherically relevant particles. AB - Inadequate knowledge of the phase state of atmospheric particles represents a source of uncertainty in global climate and air quality models. Hygroscopic aqueous inorganic particles are often assumed to remain liquid throughout their atmospheric lifetime or only (re)crystallize at low relative humidity (RH) due to the kinetic limitations of efflorescence (salt crystal nucleation and growth from an aqueous solution). Here we present experimental observations of a previously unexplored heterogeneous nucleation pathway that we have termed "contact efflorescence," which describes efflorescence initiated by an externally located solid particle coming into contact with the surface of a metastable aqueous microdroplet. This study demonstrates that upon a single collision, contact efflorescence is a pathway for crystallization of atmospherically relevant aqueous particles at high ambient RH (<=80%). Soluble inorganic crystalline particles were used as contact nuclei to induce efflorescence of aqueous ammonium sulfate [(NH4)2SO4], sodium chloride (NaCl), and ammonium nitrate (NH4NO3), with efflorescence being observed in several cases close to their deliquescence RH values (80%, 75%, and 62%, respectively). To our knowledge, these observations represent the highest reported efflorescence RH values for microdroplets of these salts. These results are particularly important for considering the phase state of NH4NO3, where the contact efflorescence RH (~20-60%) is in stark contrast to the observation that NH4NO3 microdroplets do not homogeneously effloresce, even when exposed to extremely arid conditions (<1% RH). Considering the occurrence of particle collisions in the atmosphere (i.e., coagulation), these observations of contact efflorescence challenge many assumptions made about the phase state of inorganic aerosol. PMID- 26668395 TI - Musclin is an activity-stimulated myokine that enhances physical endurance. AB - Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin-a peptide with high homology to natriuretic peptides (NP)-as an exercise-responsive myokine that acts to enhance exercise capacity in mice. We use human primary myoblast culture and in vivo murine models to establish that the activity-related production of musclin is driven by Ca(2+)-dependent activation of Akt1 and the release of musclin-encoding gene (Ostn) transcription from forkhead box O1 transcription factor inhibition. Disruption of Ostn and elimination of musclin secretion in mice results in reduced exercise tolerance that can be rescued by treatment with recombinant musclin. Reduced exercise capacity in mice with disrupted musclin signaling is associated with a trend toward lower levels of plasma atrial NP (ANP) and significantly smaller levels of cyclic guanosine monophosphate (cGMP) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in skeletal muscles after exposure to exercise. Furthermore, in agreement with the established musclin ability to interact with NP clearance receptors, but not with NP guanyl cyclase-coupled signaling receptors, we demonstrate that musclin enhances cGMP production in cultured myoblasts only when applied together with ANP. Elimination of the activity-related musclin-dependent boost of ANP/cGMP signaling results in significantly lower maximum aerobic capacity, mitochondrial protein content, respiratory complex protein expression, and succinate dehydrogenase activity in skeletal muscles. Together, these data indicate that musclin enhances physical endurance by promoting mitochondrial biogenesis. PMID- 26668397 TI - Frequency preference and attention effects across cortical depths in the human primary auditory cortex. AB - Columnar arrangements of neurons with similar preference have been suggested as the fundamental processing units of the cerebral cortex. Within these columnar arrangements, feed-forward information enters at middle cortical layers whereas feedback information arrives at superficial and deep layers. This interplay of feed-forward and feedback processing is at the core of perception and behavior. Here we provide in vivo evidence consistent with a columnar organization of the processing of sound frequency in the human auditory cortex. We measure submillimeter functional responses to sound frequency sweeps at high magnetic fields (7 tesla) and show that frequency preference is stable through cortical depth in primary auditory cortex. Furthermore, we demonstrate that-in this highly columnar cortex-task demands sharpen the frequency tuning in superficial cortical layers more than in middle or deep layers. These findings are pivotal to understanding mechanisms of neural information processing and flow during the active perception of sounds. PMID- 26668398 TI - Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer. AB - Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs ((ss)DFO-5B1, (ss)FL-5B1, and (ss)dual 5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9 positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The (ss)dual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation. PMID- 26668399 TI - Evolution of stickleback in 50 years on earthquake-uplifted islands. AB - How rapidly can animal populations in the wild evolve when faced with sudden environmental shifts? Uplift during the 1964 Great Alaska Earthquake abruptly created freshwater ponds on multiple islands in Prince William Sound and the Gulf of Alaska. In the short time since the earthquake, the phenotypes of resident freshwater threespine stickleback fish on at least three of these islands have changed dramatically from their oceanic ancestors. To test the hypothesis that these freshwater populations were derived from oceanic ancestors only 50 y ago, we generated over 130,000 single-nucleotide polymorphism genotypes from more than 1,000 individuals using restriction site-associated DNA sequencing (RAD-seq). Population genomic analyses of these data support the hypothesis of recent and repeated, independent colonization of freshwater habitats by oceanic ancestors. We find evidence of recurrent gene flow between oceanic and freshwater ecotypes where they co-occur. Our data implicate natural selection in phenotypic diversification and support the hypothesis that the metapopulation organization of this species helps maintain a large pool of genetic variation that can be redeployed rapidly when oceanic stickleback colonize freshwater environments. We find that the freshwater populations, despite population genetic analyses clearly supporting their young age, have diverged phenotypically from oceanic ancestors to nearly the same extent as populations that were likely founded thousands of years ago. Our results support the intriguing hypothesis that most stickleback evolution in fresh water occurs within the first few decades after invasion of a novel environment. PMID- 26668400 TI - Neural mechanisms of social decision-making in the primate amygdala. AB - Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions. PMID- 26668401 TI - Singular Value Decomposition of Optically-Mapped Cardiac Rotors and Fibrillatory Activity. AB - Our progress of understanding how cellular and structural factors contribute to the arrhythmia is hampered in part because of controversies whether a fibrillating heart is driven by a single, several, or multiple number of sources, and whether they are focal or reentrant, and how to localize them. Here we demonstrate how a novel usage of the neutral singular value decomposition (SVD) method enables the extraction of the governing spatial and temporal modes of excitation from a rotor and fibrillatory waves. Those modes highlight patterns and regions of organization in the midst of the otherwise seemingly-randomly propagating excitation waves. We apply the method to experimental models of cardiac fibrillation in rabbit hearts. We show that the SVD analysis is able to enhance the classification of the heart electrical patterns into regions harboring drivers in the form of fast reentrant activity and other regions of by standing activity. This enhancement is accomplished without any prior assumptions regarding the spatial, temporal or spectral properties of those drivers. The analysis corroborates that the dominant mode has the highest activation rate and further reveals a new feature: A transfer of modes from the driving to the passive regions resulting in a partial reaction of the passive region to the driving region. PMID- 26668402 TI - Current evidence for endolymphatic sac surgery in the treatment of Meniere's disease: a systematic review. AB - This paper aims to identify emerging evidence for endolymphatic sac surgery (ESS) in the treatment of Meniere's disease since the landmark study by Thomsen et al, published in 1998 (conducted from 1981 to 1989). Using the MEDLINE database (PubMed), a systematic review of the literature published from January 1990 to June 2014 was performed. We included all English-language, peer-reviewed randomised controlled trials (RCTs) and controlled studies. Single-arm cohort studies were included if the sample size was >= 90 with a response rate > 60%. Altogether, 11 studies fulfilled our inclusion criteria; one was an RCT, two were controlled trials and eight were single-arm cohort studies. There currently exists a low level of evidence for the use of ESS in the treatment of Meniere's disease. Further studies, in particular RCTs and/or controlled studies, are required to fully evaluate this modality. However, there are difficulties in designing a valid placebo and achieving adequate blinding of observers and investigators. PMID- 26668404 TI - Imaging in noncardiovascular thoracic emergencies: a pictorial review. AB - Cardiovascular and noncardiovascular conditions are commonly encountered in the emergency department. While the majority of patients have underlying cardiovascular aetiologies, such as acute myocardial infarction, congestive heart failure, aortic dissection and pulmonary embolism, a small subset of patients have underlying noncardiovascular conditions, although they present with similar symptoms of chest pain, dyspnoea, cough, haemoptysis and haematemesis. This article aims to describe the imaging findings in common noncardiovascular conditions of the chest that are frequently encountered in the emergency department, with a review of the existing literature. PMID- 26668403 TI - When babies turn yellow. AB - Neonatal jaundice is a common condition seen in the primary care setting. Most afflicted babies have physiological jaundice and their prognosis is good. However, others have pathological jaundice, which must be detected early. High levels of serum bilirubin can also result in bilirubin encephalopathy. This article describes consultation tasks in the primary care setting with the aim of providing a guide for the safe management of neonatal jaundice. They include clinical assessment of the baby's well-being; looking out for features that suggest pathological jaundice; assessment for the presence of high-risk features; utilising appropriate laboratory tests for monitoring; assessing the degree of jaundice to decide if the child can be safely followed up in primary care; and providing advice on primary prevention measures and allaying parental concerns. The importance of stool colour examination and its role in early detection of cholestatic jaundice is emphasised. PMID- 26668405 TI - Child maltreatment syndrome: demographics and developmental issues of inpatient cases. AB - INTRODUCTION: This study aimed to describe the demographic, social, developmental and behavioural profile of children hospitalised for alleged child maltreatment syndrome (CMS). METHODS: This study was a retrospective review of the consecutive inpatient records of children (0-16 years) admitted to the National University Hospital, Singapore, for alleged CMS over a three-year period. Descriptive data on the demographic characteristics, alleged maltreatment, medical and developmental histories, and family background of these children were collected and analysed. Chi-square statistics were used to test whether family factors were associated with the type of maltreatment and the presence of developmental disorders. RESULTS: A total of 89 children, who accounted for 90 admission cases, were studied. Physical abuse (70.0%) was the most common, followed by neglect (11.1%) and sexual abuse (7.8%). Child protection services had already been involved in 29.2% of the cases prior to the child's admission. Children who were victims of abuse were more likely to come from homes with a prior history of domestic violence (p = 0.028). Financial difficulty was found to be a risk factor for neglect (p = 0.005). Among the 89 children, 15.7% were found to have developmental disorders and 10.1% had mental health diagnoses. Children who had developmental disorders were more likely to have a parent with a mental health disorder (p = 0.002). CONCLUSION: A sizeable proportion of the children admitted for alleged CMS had developmental or behavioural disorders. Clinicians have a role in ensuring that these children have appropriate follow-up plans. Children from high-risk families should be screened for maltreatment. PMID- 26668406 TI - Pedestrian injuries in children: who is most at risk? AB - INTRODUCTION: This study evaluates the demographics of paediatric pedestrian injuries with the aim of identifying the group of children who is most vulnerable and the risk factors for major trauma (MT). METHODS: Data was extracted from the integrated trauma system of a regional paediatric referral hospital. All paediatric cases involving road traffic accidents from January 2011 to December 2013 were studied. Demographics, injury mechanism, treatment and outcome were evaluated. Patients were categorised as MT or non-MT (NMT) based on their Injury Severity Score, admission to the intensive care unit, type of surgery (e.g. life/limb-saving) and death. Data analysis was done using nonparametric tests and Fisher's exact test. RESULTS: A total of 261 children were admitted for pedestrian injuries during the study period. The median age was ten years (range 14 months-16 years) and the median weight was 42.4 (range 8.6-93.7) kg. Half (i.e. 50.2%) of the children were primary-schoolers. The majority of the accidents occurred on roads (i.e. 83.1%), between 12 pm and 6 pm (i.e. 52.8%). Among the 261 children, 177 (67.8%) were unaccompanied by an adult at the time of the accident; 17 (6.5%) children sustained MT, while 244 (93.5%) suffered NMT. MT patients were more likely to have lost consciousness (p < 0.001) and been flung (p = 0.001). CONCLUSION: Most paediatric pedestrian injuries involved primary schoolers walking home from school unaccompanied by adults. This information should inform future road safety campaigns. Being flung and loss of consciousness predicted MT in children who sustained pedestrian injuries. PMID- 26668407 TI - A review of oral food challenges in children presenting to a single tertiary centre with perceived or true food allergies. AB - INTRODUCTION: The prevalence of perceived food allergies exceeds that of true food allergies. Unnecessary food avoidance may increase parental and patient anxiety, reduce quality of life and increase the risk of nutritional deficiency. An oral food challenge (OFC) can provide an objective measure regarding the presence or absence of food allergies in a child. This study reviews the indications for and outcomes of OFCs performed on children. METHODS: A retrospective review was performed on all children who underwent OFCs at the Allergy Unit of the National University Hospital, Singapore, over a three-year period. RESULTS: A total of 197 OFCs were performed among 58 patients (34 male, 24 female). Most of the tests were for allergies to tree nuts (n = 107). Among the OFCs, 43.1% were for foods that were avoided and never eaten due to perceived food allergies, 25.9% were for foods that had previously resulted in positive skin prick tests (SPTs) and/or immunoassay results, 16.2% were for foods thought to worsen eczema and 14.7% were for foods thought to have caused a previous reaction. Of all the OFCs, 5% were positive, although adverse reactions were mostly cutaneous. Challenge-positive patients had either positive SPTs (wheal > 3 mm) or raised serum immunoglobulin E levels to specific foods that they reacted to during the challenges. No episodes of anaphylaxis were reported after the challenge. Most of the patients were able to safely introduce the avoided foods into their diets. CONCLUSION: OFCs provide an objective assessment for suspected food allergies. PMID- 26668408 TI - Predictors of major lower limb amputation among type II diabetic patients admitted for diabetic foot problems. AB - INTRODUCTION: Diabetes mellitus (DM) is the most common cause of amputations in Malaysia. This study aimed to identify the predictive factors for major lower limb amputation among patients with type 2 DM (T2DM) who were admitted to a hospital, in order to reduce its likelihood. METHODS: This cross-sectional study involved 218 patients with T2DM who were admitted to Hospital Tengku Ampuan Afzan, Kuantan, Malaysia, for diabetic foot problems from June 2011 to July 2012. A form was developed to document the patients' profiles, comorbidities, complications, investigations, treatment and clinical outcomes. The predictors for major lower limb amputations were determined using univariate and stepwise logistic regression analysis. RESULTS: A total of 31 patients underwent major lower limb amputations (25 transtibial, 6 transfemoral). The following factors were found to be associated with the incidence of major lower limb amputations: T2DM duration >= 10 years, diabetic neuropathy, diabetic nephropathy, presentation with gangrene, diabetic foot conditions of Wagner grade 4 or 5, and necrotising fasciitis. Patients who underwent major amputations had significantly lower haemoglobin and albumin levels, and higher total white blood cell counts, erythrocyte sedimentation rates, and C-reactive protein, urea and creatinine levels. However, only T2DM duration >= 10 years, positive bacterial culture and albumin levels were significant on stepwise logistic regression analysis. CONCLUSION: T2DM duration >= 10 years, positive bacterial culture and low albumin levels were found to be significant predictive factors for major lower limb amputation among patients with T2DM admitted for diabetic foot problems. PMID- 26668409 TI - Factors influencing the longevity and replacement frequency of Provox voice prostheses. AB - INTRODUCTION: This study aimed to assess the factors that influence the longevity and replacement frequency of Provox voice prostheses following their placement. METHODS: The medical records of 27 patients who received Provox voice prostheses after total laryngectomy and attended follow-up regularly between 1998 and 2012 were retrospectively reviewed. The success rate of the Provox voice prostheses (i.e. whether speech was achieved), quality of speech achieved, number and type of complications encountered, frequency of prostheses replacement and reasons for prostheses replacements were evaluated. RESULTS: All 27 patients were men and their mean age was 63.0 (range 43-78) years. The mean follow-up period was 60.3 (range 1-168) months. Fluent and understandable speech was achieved in 85.0% of the patients. The mean duration before prosthesis replacement had to be performed was 17.1 (range 1-36) months. The most frequent complication was fluid leakage through the prosthesis. There was a strong positive correlation of 77.1% between the longevity of prostheses and postoperative follow-up duration (r = 0.771; p < 0.01). CONCLUSION: The voice prosthesis is a tool that can be delivered in a practical fashion and replaced easily with no serious complications. It is a means by which speech can be restored, with a high success rate, after total laryngectomy. In the present study, we found that postoperative follow-up duration was the most important factor influencing the longevity of the Provox voice prosthesis. PMID- 26668410 TI - Penile cancer: a local case series and literature review. AB - INTRODUCTION: Penile cancer is an uncommon disease affecting only about one in 100,000 men worldwide in a year. The diagnosis of the condition is frequently delayed, and the disease and its treatment frequently result in significant morbidity in patients. METHODS: We herein describe seven cases of penile tumours: six cases of squamous cell carcinomas and one case of B-cell lymphoma that presented to our hospital's urology department between March 2011 and October 2012. We reviewed the literature to discuss the clinical presentation, natural history and current management of penile cancer. RESULTS: The patients were followed up for 1-24 months. They were managed according to their disease stage and lymph node status. Four out of seven patients showed disease progression during the follow-up period. CONCLUSION: The accurate staging of inguinal nodes in cases of low-risk disease is important to prescribe appropriate surgery for the inguinal nodes. Aggressive management of inguinal and pelvic lymph nodes remains the cornerstone in the treatment of high-risk disease cases. PMID- 26668411 TI - Chordoid glioma. PMID- 26668412 TI - A simple, flexible and readily applicable method of boundary construction to prevent leech migration. PMID- 26668413 TI - Counting on better health? PMID- 26668414 TI - A Journey to Kitovu. PMID- 26668415 TI - HbA1c for Diabetes Screening in Acute Coronary Syndrome: time for a reappraisal of the guidelines? AB - OBJECTIVE: Diabetes is highly prevalent in individuals with acute coronary syndrome (ACS). Current NICE guidelines recommend diabetes screening of hyperglycaemic patients using a fasting plasma glucose after 4 days from admission. In 2012 the World Health Organisation (WHO) approved the use of HbA1c in the diagnosis and targeted screening for type 2 diabetes. We introduced a service improvement project using HbA1c for diabetes screening in patients with no previous diagnosis of diabetes admitted with ACS regardless of glycaemic state. METHOD: An initial retrospective audit utilised 21 months of data from the MINAP database to identify patients meeting current NICE criteria for diabetes screening. A prospective service improvement project was undertaken over a 4 month period using HbA1c as a universal screening test to categorise ACS patients based on WHO criteria. RESULTS: The retrospective audit identified 93 of 420 (22%) patients with pre-existing diabetes and 8 of the remaining 327 (2.4%) were hyperglycaemic, thus meeting NICE criteria for diabetes screening. In the service improvement project 2/49 patients (4%) met NICE criteria for diabetes screening. Twenty six of these 49 patients had a HbA1c test on admission and 17/26 (65.4%) were classified as probable diabetes or high risk. CONCLUSION: A significant proportion of ACS patients have diabetes, which may be undetected by current NICE criteria. Universal HbA1c testing offers utility as a simple and effective screening test for diabetes in the ACS population. PMID- 26668416 TI - The male to female ratio at birth in the Republic of Ireland and Northern Ireland: influence of societal stress. AB - INTRODUCTION: Male live births occur slightly in excess of female births. The ratio of male divided by total births is referred to as M/F. Many factors reduce M/F including toxins, stress, and privation, with excess male foetal loss. "The Troubles" (1969-1998) of Northern Ireland (NI) and the economic downturn of Republic of Ireland (ROI) from 2007 posed stresses with corresponding controls. This study analysed M/F in NI and ROI. METHODS: Annual male and female live births in NI and the ROI were compared using chi tests. RESULTS: M/F was significantly higher in NI than in ROI. M/F in NI dropped after 1974. M/F rose in ROI up to 1994, then fell. DISCUSSION: Violence-related stress may have been the cause for the M/F drop in NI. Economic improvement followed by recession may have caused parallel M/F changes in ROI. These findings agree with the stress hypothesis of M/F. PMID- 26668417 TI - Intravesical chondroitin sulphate for interstitial cystitis/painful bladder syndrome. AB - INTRODUCTION: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the bladder. Bladder instillation is one avenue of treatment but evidence for its effectiveness is limited. Chondroitin sulphate solution 2.0% (Urocyst) is a glycosaminoglycan (GAG) replenishment therapy instilled for patients with IC/PBS. We assessed its effectiveness for treating IC/PBS in Northern Ireland. METHODS: Patients with IC/PBS were assessed with the O'Leary-Sant interstitial cystitis index score and global response assessment questionnaire prior to commencing treatment. Assessment with these questionnaires was performed after 6 treatments (10 weeks) and again after 10 treatments (24 weeks). Assessment end points were pain, urgency, symptom score and problem score. RESULTS: Data was collected on 10 patients, 9 female and 1 male. 6 patients had failed RIMSO-50 dimethyl sulphoxide (DMSO) 50% treatment prior. At baseline the mean pain score was 6.6, urgency score 7.00, symptom score 13.5 and problem score 12.5. After 24 weeks the mean pain score fell to 2.0, urgency score to 1.80, symptom score to 6.89 and problem score to 5.67. At 10 weeks the global response to treatment was 100%. Nocturia was the first symptom to improve with urgency and pain following. No side effects were noted during instillation and all patients tolerated the treatments. CONCLUSION: IC/PBS is a difficult disease to treat. It requires a multimodal approach. We found that intravesical chondroitin sulphate reduced pain, urgency and O'Leary-Sant symptom and problem scores in patients with IC/PBS. All patients tolerated the treatment and no side effects were reported. PMID- 26668418 TI - Assessing the need for low secure care in Northern Ireland. AB - AIMS AND METHOD: To assess the need for the provision of low secure care in Northern Ireland. A survey of the providers of healthcare in Northern Ireland was conducted using a study tool based on Royal College of Psychiatrists Low Secure Network Standards admission criteria. RESULTS: A total of 105 patients were assessed as needing low secure care including 93 patients currently admitted to hospital in the region and 12 patients admitted to hospital outside of the region. CLINICAL IMPLICATIONS: The results of this study are similar to previous estimates of need for the provision of low secure care in the UK. The results provide information likely to be of assistance in the commissioning of low secure services. DECLARATION OF INTEREST: None. PMID- 26668419 TI - Tenckhoff Peritoneal Dialysis Catheter Insertion in a Northern Ireland District General Hospital. AB - INTRODUCTION: Chronic kidney disease (CKD) affects approximately 5% of the population. Based on 2014 data, peritoneal dialysis (PD) is underutilised in Northern Ireland with a prevalence of only 11% in patients requiring renal replacement therapy (RRT). Recent National Institute of Clinical Excellence (NICE) guidelines aim to increase the rate of PD utilisation to 39% amongst patients requiring RRT. In order to implement these guidelines, nephrologists must have access to a reliable, effective PD catheter insertion service. The aim of this study was to assess the outcomes of PD catheter insertions and incident rates of PD use in a single centre in anticipation of a potential increased uptake. METHODS: A retrospective analysis was conducted of all patients who underwent PD catheter insertion between April 2003 and October 2011. Case notes were reviewed for demographic information, complications, need for re intervention, and primary catheter patency at 12 months. The UK Renal Registry annual reports were also reviewed for data on annual uptake of PD in our institution. RESULTS: Fifty-four patients underwent PD catheter insertion between 2005 and 2011; 61% were male with a median age of 58 (range 21-82) years. Early complications (<=30 days) included bowel perforation (n=1) and wound infection (n=2). During this study period 17 (31%) patients required manipulation or reinsertion for catheter obstruction/migration. The primary catheter patency at 12 months was 76%. The average uptake of PD as the first treatment modality (incident use) was 21.3% compared to a Northern Ireland (NI) average of 12.4%. CONCLUSION: Complication rates were comparable to the International Society of Peritoneal Dialysis (ISPD) guidelines in this case series and PD uptake was higher than the NI average. Therefore, local provision of an expert surgical PD catheter insertion service may potentially facilitate an increased uptake of this modality amongst RRT patients but further research is warranted. PMID- 26668420 TI - Salmonella Osteomyelitis. AB - Salmonella infection can cause four predominant clinical syndromes: enteric fever, acute gastroenteritis, bacteraemia with or without metastatic infection, and the asymptomatic carrier state. Salmonella as an aetiological agent in osteomyelitis is essentially rare and salmonella osteomyelitis in itself is predominantly seen in patients with haemoglobinopathies such as sickle cell disease or thalassemia. There are very few cases reported in the literature in which salmonella osteomyelitis is seen in otherwise healthy individuals. We describe here a case of salmonella osteomyelitis in a young gentleman with no significant comorbidities who presented with fever and severe back pain, having returned from recent foreign travel. It is therefore important to consider uncommon pathogens in the differential diagnosis of travellers with prolonged fever and insidious symptoms. PMID- 26668421 TI - Intersecting Virtual Patients and Microbiology: Fostering a culture of learning. AB - BACKGROUND: The use and integration of Technology Enhanced Learning (TEL) resources in medical education has attracted considerable commentary and support. "Virtual Patients" are one such resource. Whilst evidence exists supporting the benefits of these resources, there has not been specific consideration of their implications for teaching microbiology; nor attention paid to both the internal and external factors that influence learner engagement with virtual patients. The principle aims of this study are to identify factors that explicitly and implicitly influence the student's interaction with a microbiology virtual patient resource and how these interactions reflect upon the use of the resource. METHODS: A mixed method quantitative (online questionnaire; n=161) and qualitative (student focus groups; N=11) study was undertaken amongst third year medical students enrolled at Queen's University Belfast in the academic year 2012 2013. RESULTS: The results supported prior evidence that virtual patients are a useful learning tool (mean score of 5.09 out of 7) that helped them to integrate microbiology principles with clinical experiences. How students used the virtual patients and the depth of the subsequent benefits was dependent upon their perception of the importance of the resource. This was influenced by a number of factors including how the resources were presented and positioned within the curriculum, whether they were formally examined or timetabled and the importance attributed by peers who had already completed the examinations. CONCLUSION: Integration of virtual patients into the microbiology curriculum is widely endorsed and may even be considered superior to other methods of teaching. How students use these resources is dependent upon a positive perception of their importance. Educators should be aware of the factors that shape this perception when integrating TEL resources into curricula. PMID- 26668422 TI - Anthony Traill (1838-1914), the first Provost to confer degrees on Women Graduates. AB - Anthony Traill was born into a Scotch-Irish family at Ballylough House near Bushmills in county Antrim in November 1838. At the age of twenty he entered Trinity College Dublin to study engineering, but he was a professional student who passed through all the faculties and took legal and medical degrees in 1864 1870. He applied his knowledge of physics when advising his brother William who was building the Portrush-Bushmills electric railway. Though he took time off to indulge his athletic abilities, he steeped himself in College affairs and became Provost in March 1904, a post he held until his death in October 1914. His outstanding contribution whilst holding that post was to welcome women with university training into graduation. PMID- 26668423 TI - Battle of the Atlantic: Military and Medical Role of Northern Ireland (After Pearl Harbor). PMID- 26668425 TI - ERRATUM. PMID- 26668424 TI - TWIDDLER'S SYNDROME. PMID- 26668426 TI - Curiositas. PMID- 26668427 TI - Game Changers. PMID- 26668428 TI - So you want to be a Medical Volunteer. PMID- 26668430 TI - Learning from Ebola: readiness for outbreaks and emergencies. PMID- 26668431 TI - Climate change and health in Pacific island states. PMID- 26668432 TI - Europe gears up to attend to refugees' health. PMID- 26668433 TI - WHO steps up its role in health emergencies. PMID- 26668434 TI - Tuberculosis-associated mortality in Shanghai, China: a longitudinal study. AB - OBJECTIVE: To determine excess mortality in a cohort of people with tuberculosis in Shanghai. METHODS: Participants were local residents in 4 (of 19) districts in Shanghai, registered in one of four tuberculosis clinics between January 1, 2004 and December 31, 2008. Baseline data were collected at the most recent diagnosis of tuberculosis and mortality was assessed between March and May of 2014. We calculated standardized mortality ratios (SMR) and case-fatality rates for all participants and for subgroups. Univariate and multivariate Cox regression models were used to quantify associations between co-morbidities and mortality from all causes and from tuberculosis. FINDINGS: We registered 4569 subjects in the cohort. Overall, the cohort had an SMR for deaths from all causes of 5.2 (95% confidence interval, CI: 4.8-5.6). Males had a higher SMR than females (6.1 versus 3.0). After adjustment for age and sex, hazard ratios (HR) for deaths from all causes were significantly greater in previously treated people (HR: 1.26; 95% CI: 1.08-1.49) and sputum smear-test positive people (HR: 1.55; 95% CI: 1.35 1.78). The risk of death from tuberculosis was also significantly greater for previously treated people (HR: 1.88; 95% CI: 1.24-2.86) and smear positive people (HR: 3.16; 95% CI: 2.06-4.87). CONCLUSION: People with tuberculosis in Shanghai have an increased risk of mortality. Earlier diagnosis and more vigilant follow up may help to reduce mortality in this group. PMID- 26668435 TI - Improving outcomes for caregivers through treatment of young people affected by war: a randomized controlled trial in Sierra Leone. AB - OBJECTIVE: To measure the benefits to household caregivers of a psychotherapeutic intervention for adolescents and young adults living in a war-affected area. METHODS: Between July 2012 and July 2013, we carried out a randomized controlled trial of the Youth Readiness Intervention--a cognitive-behavioural intervention for war-affected young people who exhibit depressive and anxiety symptoms and conduct problems--in Freetown, Sierra Leone. Overall, 436 participants aged 15-24 years were randomized to receive the intervention (n = 222) or care as usual (n = 214). Household caregivers for the participants in the intervention arm (n = 101) or control arm (n = 103) were interviewed during a baseline survey and again, if available (n = 155), 12 weeks later in a follow-up survey. We used a burden assessment scale to evaluate the burden of care placed on caregivers in terms of emotional distress and functional impairment. The caregivers' mental health--i.e. internalizing, externalizing and prosocial behaviour--was evaluated using the Oxford Measure of Psychosocial Adjustment. Difference-in-differences multiple regression analyses were used, within an intention-to-treat framework, to estimate the treatment effects. FINDINGS: Compared with the caregivers of participants of the control group, the caregivers of participants of the intervention group reported greater reductions in emotional distress (scale difference: 0.252; 95% confidence interval, CI: 0.026-0.4782) and greater improvements in prosocial behaviour (scale difference: 0.249; 95% CI: 0.012 0.486) between the two surveys. CONCLUSION: A psychotherapeutic intervention for war-affected young people can improve the mental health of their caregivers. PMID- 26668436 TI - Effect of a mobile phone-based intervention on post-abortion contraception: a randomized controlled trial in Cambodia. AB - OBJECTIVE: To assess the effect of a mobile phone-based intervention (mHealth) on post-abortion contraception use by women in Cambodia. METHODS: The Mobile Technology for Improved Family Planning (MOTIF) study involved women who sought safe abortion services at four Marie Stopes International clinics in Cambodia. We randomly allocated 249 women to a mobile phone-based intervention, which comprised six automated, interactive voice messages with counsellor phone support, as required, whereas 251 women were allocated to a control group receiving standard care. The primary outcome was the self-reported use of an effective contraceptive method, 4 and 12 months after an abortion. FINDINGS: Data on effective contraceptive use were available for 431 (86%) participants at 4 months and 328 (66%) at 12 months. Significantly more women in the intervention than the control group reported effective contraception use at 4 months (64% versus 46%, respectively; relative risk, RR: 1.39; 95% confidence interval, CI: 1.17-1.66) but not at 12 months (50% versus 43%, respectively; RR: 1.16; 95% CI: 0.92-1.47). However, significantly more women in the intervention group reported using a long-acting contraceptive method at both follow-up times. There was no significant difference between the groups in repeat pregnancies or abortions at 4 or 12 months. CONCLUSION: Adding a mobile phone-based intervention to abortion care services in Cambodia had a short-term effect on the overall use of any effective contraception, while the use of long-acting contraceptive methods lasted throughout the study period. PMID- 26668438 TI - Rapid diagnostic tests for malaria. AB - Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID- 26668439 TI - Strategies for achieving global collective action on antimicrobial resistance. AB - Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials--ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework. PMID- 26668440 TI - The environmental and health impacts of tobacco agriculture, cigarette manufacture and consumption. AB - The health consequences of tobacco use are well known, but less recognized are the significant environmental impacts of tobacco production and use. The environmental impacts of tobacco include tobacco growing and curing; product manufacturing and distribution; product consumption; and post-consumption waste. The World Health Organization's Framework Convention on Tobacco Control addresses environmental concerns in Articles 17 and 18, which primarily apply to tobacco agriculture. Article 5.3 calls for protection from policy interference by the tobacco industry regarding the environmental harms of tobacco production and use. We detail the environmental impacts of the tobacco life-cycle and suggest policy responses. PMID- 26668437 TI - The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries. AB - OBJECTIVE: To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing. METHODS: Between 2009 and 2012, a kilometre long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders. FINDINGS: Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities. CONCLUSION: Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low income countries and urban communities. PMID- 26668441 TI - A telemedicine network for remote paediatric cardiology services in north-east Brazil. AB - PROBLEM: Providing health care for children with congenital heart diseases remains a major challenge in low- and middle-income countries. APPROACH: In October 2011, the Government of Paraiba, Brazil, established a paediatric cardiology network in partnership with the nongovernmental organization Circulo do Coracao. A cardiology team supervised all network activities, using the Internet to keep in contact with remote health facilities. The network developed protocols for screening heart defects. Echocardiograms were performed by physicians under direct online supervision of a cardiologist; alternatively, a video recording of the examination was subsequently reviewed by a cardiologist. Cardiovascular surgeons came to a paediatric hospital in the state capital once a week to perform heart surgeries. LOCAL SETTING: Until 2011, the State of Paraiba had no structured programme to care for children with heart disease. This often resulted in missed or late diagnosis, with adverse health consequences for the children. RELEVANT CHANGES: From 2012 to 2014, 73,751 babies were screened for heart defects and 857 abnormalities were identified. Detection of congenital heart diseases increased from 4.09 to 11.62 per 1000 live births (P < 0.001). Over 6000 consultations and echocardiograms were supervised via the Internet. Time to diagnosis, transfers and hospital stays were greatly reduced. A total of 330 operations were carried out with 6.7% (22/330) mortality. LESSONS LEARNT: Access to an echocardiography machine with remote supervision by a cardiologist improves the detection of congenital heart disease by neonatologists; virtual outpatient clinics facilitate clinical management; the use of Internet technology with simple screening techniques allows resources to be allocated more efficiently. PMID- 26668442 TI - Including migrant populations in health impact assessments. PMID- 26668443 TI - A practical implementation science heuristic for organizational readiness: R = MC2. AB - There are many challenges when an innovation (i.e., a program, process, or policy that is new to an organization) is actively introduced into an organization. One critical component for successful implementation is the organization's readiness for the innovation. In this article, we propose a practical implementation science heuristic, abbreviated as R= MC2 . We propose that organizational readiness involves: 1) the motivation to implement an innovation, 2) the general capacities of an organization, and 3) the innovation-specific capacities needed for a particular innovation. Each of these components can be assessed independently and be used formatively. The heuristic can be used by organizations to assess readiness to implement and by training and technical assistance providers to help build organizational readiness. We present an illustration of the heuristic by showing how behavioral health organizations differ in readiness to implement a peer specialist initiative. Implications for research and practice of organizational readiness are discussed. PMID- 26668444 TI - Beyond tobacco in head and neck squamous cell cancers... Emerging era of molecular targeted therapy and virtual biopsy. PMID- 26668445 TI - Technical complications of implant-causes and management: A comprehensive review. AB - Given the increasing popularity of dental implants, the number of failures due to late implant fracture is also expected to increase. Hence, the scope for prevention and management needs to be emphasized. The objective of this review article is to analyze the various causes of failure of dental implants due to implant fixture/abutment screw fractures and also to enumerate the management and the preventive options for these failures, thereby aiming to help the clinicians to properly plan the implant-supported prosthesis treatment by considering the important biomechanical aspects of this type of rehabilitation. The present review emphasizes the causes and management of technical complications and not the incidence of such complications. PMID- 26668446 TI - Molecular concept in human oral cancer. AB - The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor alpha [TGF-alpha], TGF-beta, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy. PMID- 26668447 TI - Temporomandibular joint dislocation. AB - Temporomandibular joint (TMJ) dislocation is an uncommon but debilitating condition of the facial skeleton. The condition may be acute or chronic. Acute TMJ dislocation is common in clinical practice and can be managed easily with manual reduction. Chronic recurrent TMJ dislocation is a challenging situation to manage. In this article, we discuss the comprehensive review of the different treatment modalities in managing TMJ dislocation. PMID- 26668448 TI - Clinical profile and epidemiological factors of oral cancer patients from North India. AB - INTRODUCTION: Tobacco chewing, smoking, and alcohol consumption are major contributing factors in the development of oral carcinoma. India has world's highest number of oral cancers (almost 20%) and approximately 1% of the Indian population has oral premalignant lesions. AIM: The purpose of the study was to evaluate the epidemiological factors and clinical profile of oral cancer cases in our hospital. SETTINGS: Department of Surgical Oncology, King George's Medical University, Lucknow, India. MATERIALS AND METHODS: A retrospective study was conducted from January 2010 to December 2012 on 479 cases with histopathologically confirmed oral carcinoma. Subjects' details of age, sex, occupation, tobacco consumption, site of carcinoma, and stage at presentation were recorded. RESULTS: Mean age in this study was 47.84 years with male to female ratio of 3.1:1.0. Buccal mucosa and alveolus were the most affected sites. The majority of cases were from socially and economically weaker section, with 93.72% cases being tobacco users. The majority of cases were advance stage (Stage III and IV) with Stage IV being the predominant stage at presentation followed by Stage III. CONCLUSION: The findings of the study reveal that tobacco consumption is one of the major contributors in the development of cancer of oral cavity with the majority of cases presenting in advance stages posing a big therapeutic challenge. PMID- 26668449 TI - A study of lip prints and its reliability as a forensic tool. AB - INTRODUCTION: Lip prints, like fingerprints, are unique to an individual and can be easily recorded. Therefore, we compared direct and indirect lip print patterns in males and females of different age groups, studied the inter- and intraobserver bias in recording the data, and observed any changes in the lip print patterns over a period of time, thereby, assessing the reliability of lip prints as a forensic tool. MATERIALS AND METHODS: Fifty females and 50 males in the age group of 15 to 35 years were selected for the study. Lips with any deformity or scars were not included. Lip prints were registered by direct and indirect methods and transferred to a preformed registration sheet. Direct method of lip print registration was repeated after a six-month interval. All the recorded data were analyzed statistically. RESULTS: The predominant patterns were vertical and branched. More females showed the branched pattern and males revealed an equal prevalence of vertical and reticular patterns. There was an interobserver agreement, which was 95%, and there was no change in the lip prints over time. Indirect registration of lip prints correlated with direct method prints. CONCLUSION: Lip prints can be used as a reliable forensic tool, considering the consistency of lip prints over time and the accurate correlation of indirect prints to direct prints. PMID- 26668450 TI - Retrospective study of mandibular angle fractures treated with three different fixation systems. AB - AIM: To evaluate the outcomes of mandibular angle fractures treated with metal 2.0 mm locking, metal 2.0 mm nonlocking, and 2.5 mm resorbable systems. STUDY DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Trauma records were screened for linear angle fractures treated with open-reduction and internal semi rigid fixation with single metal/bioresorbable plates, and baseline variables were tabulated. The outcome variable was the presence or absence of any complication. STATISTICAL ANALYSIS USED: The Fisher's exact test and analysis of covariance (ANCOVA) using STATA 11. RESULTS: A total of 60 case records of over four years were included. The mean age of the patients was 27.4 (SD 9.7) years. Fifty-five were male and five female. There were 20 nonlocking and 16 locking metal miniplates and 24 bioresorbable plates. In 55 (91.6%) cases there was a third molar in the fracture line. In 51/55 (92.7%) cases the third molar was retained. In seven patients postoperative complications were seen. There was no difference between the complication rates of the three treatment groups. Infection was the most common complication followed by delayed union and hardware failure. CONCLUSIONS: This retrospective study found no difference in the complication rate when fractures of the mandibular angle were treated with locking or nonlocking miniplates or bioresorbable plates. PMID- 26668451 TI - Pectoralis major myocutaneous flap in head and neck reconstruction: An experience in 100 consecutive cases. AB - BACKGROUND: The pectoralis major myocutaneous (PMMC) flap has been used as a versatile and reliable flap since its first description by Ariyan in 1979. In India head and neck cancer patients usually present in the advanced stage making PMMC flap a viable option for reconstruction. Although free flap using microvascular technique is the standard of care, its use is limited by the availability of expertise and resources in developing world. The aim of this study is to identify the outcomes associated with PMMC flap reconstruction. PATIENTS AND METHODS: After ethical approval we retrospectively analyzed 100 PMMC flap at a tertiary care hospital from 2006 to 2013. A total of 137 PMMC flap reconstructions were performed out of which follow-up data of 100 cases were available in our record. RESULTS: A total of 100 patients were reviewed of these 86% were of oral cavity and oropharyngeal lesions, 8% were of hypopharyngeal, 3% were of laryngeal malignancies and 3 cases were of salivary gland tumor. Most tumors (83%) were advanced (T3 or T4 lesion). 95 PMMC flap reconstruction were done as a primary procedure, and 5 were salvage procedure. PMMC flap was used to cover mucosal defect in 84 patients, skin defects in 10 patient and both in 6 patients. Overall flap related complications were 40% with a major complication in 10% and minor complications in 30%. No total flap loss occurred in any patient, major flap occurred in 6% and minor flap loss in 12%. In minor flap loss patients, necrotic changes were mostly limited to skin. Orocutaneous and pharyngocutaneous fistula developed in 12 patients. 10% patients required re surgery after developing various flap related complications Pleural empyema developed in 3 patients. Other minor complications such as neck skin dehiscence and intra-oral flap dehiscence developed in 26 patients. CONCLUSION: PMMC flap is a versatile flap with an excellent reach to face oral cavity and neck region. With limited expertise and resources, it is still a workhorse flap in head and neck reconstruction. PMID- 26668452 TI - Comparison of pharyngeal airway dimension, tongue and hyoid bone position based on ANB angle. AB - OBJECTIVE: This study was undertaken to cephalometrically evaluate the pharyngeal airway dimension, tongue and hyoid position in subjects with normal nasorespiratory functions having different dentofacial patterns (A-point-nasion-B point [ANB] >40 and ANB <40) and to find if a correlation existed. MATERIALS AND METHODS: Class I and Class II Division I patients were selected randomly. Lateral head cephalograms were taken in normal head position within a lead foil attached to the tongue tip and a barium coating on the dorsal surface of tongue. The lateral cephalograms obtained were traced using lead acetate paper and measurements were taken. Different analyses were done for the pharyngeal airways, hyoid bone, and tongue. RESULTS: The ANB angle is a significant predictor for Class I and Class II Division I malocclusion, and the mean ANB angle of Class II Division I was different and higher. The overall mean pharynx and hyoid parameters were different and lower in Class II Division I patients than in Class I patients. The mean tongue parameter almost remained the same except for the tongue position (TT-LOP), which was higher in Class II Division I. CONCLUSION: In general, there was no difference either in the pharyngeal airway anterioposterior dimension or in the position and relationship of the hyoid bone and tongue, between Class I and Class II Division I patients. These findings are consistent with the findings in studies. Anterioposterior dimension of the upper airway is usually maintained by adaptation of both the tongue and the hyoid bone. The result should be viewed in the light of the fact that only anterioposterior dimensions were taken into consideration; the vertical and transverse dimensions of these complex anatomical structures need to have newer three-dimensional (3-D) imaging technique to find if a correlation existed between them, making future studies more comprehensive. PMID- 26668453 TI - Comparison of the diagnostic yield of medical and dental referrals an oral and maxillofacial 2 weeks rule clinic. AB - BACKGROUND: The 2 weeks wait clinic initiative is used as a fast track referral process, to assess patients with suspected cancer. The United Kingdom's National Institute of Clinical Excellence has issued guidelines for which patients should be referred to this service for suspected oral, head and neck cancers. Both general medical practitioners (GMPs) and general dental practitioners (GDPs) can refer to this service. OBJECTIVE: To ascertain how many of the 2 weeks rule referrals resulted in positive oncology cases. Also, to compare the diagnostic yield of cancer diagnoses between referrals from GMPs and GDPs. METHODS: Collection and analysis of 2 weeks rule referrals and the clinical outcome for these patients, to an oral and maxillofacial surgery unit for a 6 months period. RESULTS: Overall, 65% of the patients seen in the clinic were referred by a GMP and 12.5% of these had a diagnosis of cancer. The remaining 35% were referred by a GDP and 10% of these had cancer. There was no statistically significant different diagnostic yield between the two groups. CONCLUSION: A significant number of patients with confirmed cancer are referred from medically qualified practitioners. Further awareness and education of oral, head and neck cancers is warranted in this group, including at an undergraduate level. PMID- 26668454 TI - Evaluation of ultrasonography as a diagnostic tool in the management of head and neck facial space infections: A clinical study. AB - INTRODUCTION: Superficial facial space infections represent a significant amount of the dental problems that present to hospital. Determining whether an odontogenic swelling is a cellulitis or abscess is difficult, but important as both may require different treatments. The use of an ultrasound may aid in differentiating cellulitis and abscess. This study was done to compare the accuracy of clinical examination alone versus ultrasonography (USG) in the diagnosis of cellulitis and abscess in symptomatic patients with a diagnosis of superficial facial space infection. MATERIALS AND METHODS: Twenty patients (1870 years) diagnosed as superficial facial space infections by clinical and radiographic examinations were included in the study and patients with significant medical conditions were excluded. The provisional clinical diagnosis was made after a thorough history was taken and clinical examination was performed to determine if the swelling was a cellulitis or abscess. Swelling was then evaluated using the ultrasonic transducer which was placed over the swelling to aid the diagnosis which was again recorded. An incision and drainage procedure was performed after the administration of local anesthesia. The success of the ultrasound intervention versus clinical examination was based on whether frank exudation was detected during incision and drainage of such swellings. RESULTS: The statistical analysis found that USG is a valuable diagnostic aid for detection of abscess or cellulitis in head and neck facial space infections. INTERPRETATION AND CONCLUSION: The findings of this prospective analysis indicate that there was statistical difference between clinical examination alone and USG in making the correct diagnosis. The sensitivity, specificity, positive predictive, negative predictive, and accuracy were not similar for all methods tested. From the results of this study, ultrasound is recommended as an adjunct to clinical examination in differentiating between cellulitis and abscess. PMID- 26668455 TI - Release of nickel and chromium ions in the saliva of patients with fixed orthodontic appliance: An in-vivo study. AB - INTRODUCTION: Various components of fixed orthodontic appliances are continuously interacting with saliva and other fluids in the mouth releasing various metal ions including nickel and chromium that can cause damaging effects if their concentration exceeds above the toxic dose. AIM: To determine and compare the level of nickel and chromium in the saliva of patients undergoing fixed orthodontic treatment at different time periods. MATERIALS AND METHODS: The sample of saliva of 13 patients was taken at different time periods that is: Group 1 (before appliance placement), Group II, III, and IV (after 1-week, 1 month, and 3 months of appliance placement respectively). The fixed appliance comprised of brackets, bands, buccal tubes, lingual sheath, transpalatal arch and wires composed of Ni-Ti and stainless steel. The level of ions was determined using graphite furnace atomic absorption spectro-photometry. The data thus obtained were statistically analyzed using SPSS Statistical Analysis Software (Version 15.0). RESULTS: Level of nickel and chromium in saliva was highest in Group II and lowest in Groups I for both the ions. On comparison among different Groups, it was statistically significant for all the groups (<0.001) except between Group III and Group IV. CONCLUSION: The release of nickel and chromium was maximum at 1-week and then the level gradually declined. These values were well below the toxic dose of these ions. The results should be viewed with caution in subjects with Ni hypersensitivity. PMID- 26668456 TI - Comparative evaluation of topical application of turmeric gel and 0.2% chlorhexidine gluconate gel in prevention of gingivitis. AB - INTRODUCTION: Turmeric commonly known as "Haldi" is a popular spice frequently used in Indian foods and curry. Turmeric holds a high place in Ayurvedic medicine as a "detoxifier of the body," and today, science has documented several diseased conditions that can be healed by the active ingredients of turmeric. Curcumin is the most active constituent of turmeric curcuminoids obtained from the rhizome of Curcuma longa. Curcumin has been found to have antioxidant, anti-tumor, anti inflammatory, antiviral, antibacterial, antifungal, analgesic, anti-allergic, antiseptic properties and thus has a potential against various diseases. Due to these properties it was felt that promotion of turmeric in dental practice may prove beneficial. MATERIALS AND METHODS: The study was conducted in the Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, India. A total of 40 subjects of both the sexes from age group 20-35 years. Simple random sampling was followed and the participants were assigned to two groups 'A' and 'B' of 20 participants each. Group A subjects were advised 0.2% chlorhexidine gluconate gel. Group B 30 subjects were advised experimental (turmeric) gel. STATISTICAL ANALYSIS: Data were summarized as mean +/- SD. Pre and post outcome measures of two groups were compared by repeated measures analysis of variance (RM ANOVA) using general linear models (GLM) and the significance of mean difference within and between the groups was done by Bonferroni post hoc test after adjusting for multiple contrasts (comparisons). CONCLUSIONS: Based on the observations of our study, it can be concluded that chlorhexidine gluconate as well as turmeric gel can be effectively used as an adjunct to mechanical plaque control in prevention of plaque and gingivitis. chlorhexidine gluconate gel has been found to be more effective when antiplaque and anti-inflammatory properties were considered. The effect of turmeric observed may be because of its anti-inflammatory action. The antiplaque action of chlorhexidine gluconate is due to its substantivity. Substantivity of tutmeric is required to be further studied. PMID- 26668457 TI - Forehead flap in maxillofacial surgery: Our experiences. AB - The forehead flap is a commonly used technique to reconstruct the deep and large nasal defects. It can be conveniently performed under local or general anesthesia and provides a very good color and texture matching to the nasal skin, which makes it a suitable graft harvesting site for nasal reconstruction. It has only single disadvantage disadvantagethat it is a two-stage procedure and "finishing" surgeries are needed occasionally for best surgical and cosmetic outcome. In this paper, we describe three different applications of forehead flaps. PMID- 26668458 TI - Solitary plasmacytoma of the mandible: A rare case report. AB - Plasmacytoma is a monoclonal, neoplastic proliferation of plasma cells that usually arises within bone marrow or soft tissue sites. It can involve either a single bone (solitary) or multiple bones. Solitary plasmacytoma has a predisposition for the red marrow-containing axial skeleton and is most frequently seen in the thoracic vertebrae, followed by the ribs, sternum, clavicle, or scapula. Its presence in the jaws is extremely rare. We present a case of a 54-year-old female with a well-defined radiolucency of the body region of the mandible later diagnosed as solitary plasmacytoma. PMID- 26668459 TI - Use of anterior maxillary distraction osteogenesis in two cleft lip and palate patients. AB - Distraction osteogenesis (DO) has become a mainstream surgical technique for patients with jaw deformities. The aim of this study was to report the effect of DO done by a hyrax screw incorporated in an acrylic plate in the treatment of two maxillary deficient cases with cleft lip and palate. Two patients, a 24-year-old female and a 29-year-old male who suffered from maxillary deficiency and cleft lip and palate, were treated by DO. After making vertical cuts between the premolars on both sides and horizontal cuts similar to Le Fort 1, a hyrax screw was mounted on an acrylic plate for the slow anteroposterior expansion of maxillary arch. The expansion was achieved by turning the hyrax screw 0.8 mm per day after the latency period. Treatment was discontinued after achieving satisfactory over jet and occlusion. This study showed that anterior maxillary distraction is a reliable technique for correction of midfacial deformity arising out of cleft lip and palate. Incidences of complications are negligible compared to total maxillary distraction. PMID- 26668460 TI - Use of carbon dioxide laser in oral soft tissue procedures. AB - Lasers have been introduced in dentistry as an alternative to conventional knife surgery. The advantage to the operator includes a clean dry field that enhances visibility and reduces the procedure time. The patient benefits by minimal postoperative pain and swelling. The paper discusses use of carbon dioxide laser in five conditions commonly encountered in oral cavity. PMID- 26668461 TI - Giant submandibular gland duct sialolith mimicking an impacted canine tooth. AB - Sialolithiasis is the most common disease affecting the salivary glands and accounts for 80% of salivary gland disorders. Chronic sialolithiasis promotes stone formation. Size of the salivary stones may range from 0.1 mm to 30 mm or be even bigger. Those salivary stones, the size of which exceeds 15 mm in any one dimension or 1 g in weight are classified as giant sialoliths. Giant sialoliths of the submandibular gland duct are rarely reported. Here, we report a case of a giant sialolith of the submandibular gland duct mimicking an impacted mandibular canine tooth on routine radiographic examination and its surgical management through an intraoral approach. PMID- 26668462 TI - Post-operative acute circulatory collapse following craniofacial surgery: Rare event and rarer cause. AB - We are presenting a case of a 13-year-old female patient diagnosed and operated for maxillary odontogenic myxoma extending to the anterior cranial base. The postoperative complication occurred in the form of acute circulatory collapse. The patient was bailed out with cardiopulmonary resuscitation and return of spontaneous circulation occurred. Investigations into the cause of the event led to the finding of an uncommon syndrome. Meigs syndrome is a triad of ovarian tumor mass, pleural effusion and ascites. It has been the topic of interest for the gynecologic fraternity since 1934, when the first case was reported by J. V. Meigs. According to the best of our knowledge, this is the first case report of an acute circulatory collapse due to Meigs syndrome in a maxillofacial patient. PMID- 26668463 TI - Spontaneous sublingual space hematoma secondary to hypertension: A case report and review of literature. AB - Sublingual hematoma is a rare complication of oral anticoagulant use. Spontaneous sublingual hematoma secondary to hypertension is even rarer and their management remains enigmatic. We present such a case that we successfully managed conservatively along with a review of relevant literatures. PMID- 26668464 TI - NHL - Extranodal T-cell lymphoma. AB - Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare lymphoid neoplasm that in the past has been grouped with a variety of granulomatous diseases. ENKL occurs in all age groups. However, it seems to occur more often in people in their 50s and affects more men than women. It is strongly linked to the Epstein Barr virus (EBV), especially in people of Asian countries. Because this type of lymphoma occurs in organs or tissues other than lymph nodes, it is called ENKL. This is a case report of a 25-year-old female patient who presented with a nonhealing ulcer at the right nasal ala involving the upper lip and cheek for the last 2 months, which had been treated with antitubercular treatment without success. After biopsy and immunohistochemical (IHC) analysis, the patient had been diagnosed a case of extranodal T-cell lymphoma. PMID- 26668465 TI - Oral malignant melanoma: Report of three cases with literature review. AB - Primary oral melanoma is known to be an extremely rare and aggressive neoplasm arising from the mucosal epithelium of the oral cavity especially upper jaw (palate or alveolar gingivae). Malignant melanoma that does not originate in the skin is a very rare disease and is considered one of the most deadly of all human neoplasms. Oral malignant melanoma (OMM) represents about 1% of all melanomas and approximately 0.5% of all oral malignancies. OMM has been reported in patients aged 20 to 80 years and has a male predilection. Because most mucosal melanotic lesions are painless in their early stages, so delayed recognition and subsequent treatment result in worst prognosis. Here, we report three cases with significant heterogeneity in morphological features and biologic behavior. PMID- 26668466 TI - Ortho-surgical management of skeletal Class III malocclusion. AB - Class III malocclusions are considered to be one of the most difficult problems to treat. Establishment of the treatment plan is based on the efficacy and thoughtful application by the clinician and easy acceptance by the patient. We are presenting a case report of an adult male patient with skeletal Class III malocclusion who was treated by orthosurgical approach in Department of Orthodontics in collaboration with Department of Oral and Maxillofacial Surgery. The treatment was complete with a positive overbite and acceptable occlusion and satisfactory facial esthetics using a combination approach. PMID- 26668467 TI - Malignant melanoma maxilla. AB - A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis. PMID- 26668468 TI - A rare case report of grade III gingival enlargement associated with chronic periodontitis: Comparison of two treatment techniques. AB - Idiopathic gingival enlargement (GE) is a rare entity characterized by massive enlargement of the gingiva. It may be associated with other diseases/conditions characterizing a syndrome, but rarely documented in literature occurring along with chronic periodontitis. This case report describes a rare case of long standing massive GE in a systemically healthy, nonsyndromic young female involving both the arches, thereby posing a diagnostic dilemma. Furthermore, in this case, we compared two surgical approaches, that is, scalpel and electrosurgery for the convenience as well as the postoperative comfort of the patient. Quadrants 1 and 3 were treated by ledge and wedge technique using scalpel and blade while quadrants 2 and 4 were treated by electrosurgery. The patient was followed postoperatively up to 1-year. The massive GE subsided without recurrence and patient was completely satisfied with the treatment, though better compliance was observed at the site treated by conventional scalpel and blade technique. PMID- 26668469 TI - Unusual mandibular condylar pathology: Aneurysmal bone cyst, a case report and review on reconstruction. AB - Aneurysmal bone cysts (ABCs) involving condyle are unusual clinical presentation affecting younger group of society with only 12 cases reported till today in English literature. In this case of ABC condyle following resection, reconstruction of temporomandibular joint was done by alloplastic condylar prosthesis as a primary choice. Monthly basis follow-up was done for 1-year with a successful result. Reviewing the reconstructive options used in ABC condyle cases we found that the condylar head add-on system has shown a satisfactory result in comparison to costochondral graft with no donor site morbidity. We recommend condylar head add-on system should be preferred as a primary reconstructive option, reserving the autograft for recurrence cases. PMID- 26668470 TI - Juxtacortical osteosarcoma of the mandible: Challenges in diagnosis and management. AB - Parosteal osteosarcoma (OS) of the jaw is a rare type of OS with peculiar clinical radiographic and microscopic features. The aim of this article was to report and discuss a case of high-grade parosteal OS in the mandible of a 35-year old woman. The patient reported sensing mild pain and swelling in the retro molar area on the left side of the mouth for a period of 4 years, despite continuous dental treatment. The radiographic evaluation showed a mixed radiopaque/radiolucent lesion in the body of the left side of the mandible. Destruction of the mandibular cortex in that area was also observed. After the initial histological study, the patient underwent partial hemi-mandibulectomy. Microscopic findings showed a tumor exhibiting spindle cells with nuclear hyperchromasia, moderate pleomorphism, and irregular osteoid formation, with chondroid differentiation noted with tumor-free margins. The immunohistochemical analysis showed the expression of negativity to p53, human epidermal growth factor receptor 2/neu, and positivity to S-100. The diagnosis was high-grade parosteal OS of the jaw. The 4 years clinical and imaging postoperative follow-up showed no evidence of recurrence. The literature on this unusual pathologic entity reviewed and diagnostic challenges described. PMID- 26668471 TI - How safe is therapeutic dose of lignocaine with epinephrine: An overview. PMID- 26668473 TI - Evaluation of Microleakage of Silorane and Methacrylate Based Composite Materials in Class I Restorations by Using Two Different Bonding Techniques. AB - BACKGROUND: To evaluate the microleakage of silorane-based composite material (Filtek P90) with that of two homologous methacrylate-based composites materials (Filtek Z250 and Filtek Z250 XT), by using two different bonding techniques. MATERIALS AND METHODS: Sixty extracted human maxillary first premolars prepared for standardized Class I cavities (4 mm * 2 mm * 2 mm) were randomly divided into three groups. Group A (n = 20) was filled with Filtek Z250 (Methacrylate) using single bond universal total etching technique, Group B (n = 20) was filled with Filtek Z250 XT (Methacrylate) using single bond universal self-etching technique and Group C (n = 20) restored with Filtek P90 (Silorane) with dedicated two-step self-etching prime and bond adhesive system (P90 system adhesive). Teeth were subjected to thermocycling regime (500*, 5-55 degrees C), and dye penetration by immersing in 2% methylene blue for 24 h. Tooth sectioning was performed, and extent of the dye penetration was scored based on dye penetration scale to evaluate the microleakage. Statistical analysis included descriptive statistics and inferential statistics of Kruskal-Wallis test to compare the mean ranks between groups. RESULTS: There was no significant difference observed for microleakage among the three composite materials tested in the present study. However, the cavities restored with silorane (Filtek P90) based composite displayed higher microleakage than the Filtek Z250, Z250 XT. CONCLUSION: All the restorative systems tested in this study exhibited microleakage, but the silorane technology showed more microleakage when compared to the methacrylate-based composite systems. PMID- 26668474 TI - Efficacy of Sex Determination from Human Dental Pulp Tissue and its Reliability as a Tool in Forensic Dentistry. AB - BACKGROUND: Sex determination is one of the primary steps in forensics. Barr body can be used as a histological method for identification of sex as it is found to be specific to female somatic cells and rare in male cells. To demarcate human dental pulp as an important identification tool of sex in forensic odontology (FO) and to evaluate the time period till which sex can be determined from pulp tissue using three stains H and E, Feulgen, and acridine - orange under fluorescence so as. MATERIALS AND METHODS: 90 pulp samples (45 males and 45 females) were subjected to Barr body analysis for determination of sex using light and fluorescent microscopy. RESULTS: Barr body was found to be positive for female samples and negative or rare in the male sample (<3%). CONCLUSION: Barr body from human dental pulp tissue can be used as a successful determinant of sex identification in FO. PMID- 26668472 TI - Proliferative Activity of Myoepithelial Cells in Irradiated Rabbit Parotid and Submandibular Salivary Glands. AB - BACKGROUND: The behavior of salivary myoepithelial cells (MEC) during chronic irradiation exposure is unknown. This study aimed to investigate the response of MEC to prolonged radiation exposure. MATERIALS AND METHODS: 16 rabbits and four controls were irradiated with either 10 Gy, 20 Gy, 30 Gy or 40 Gy (Gray units) of direct axial beam radiation. Parotid and submandibular glands were removed and examined using immunohistochemical double staining. Proliferating MEC were semi quantified using alpha smooth muscle actin antibodies and proliferating cell nuclear antigen (PCNA) antibodies. RESULTS: MEC proliferative activity increased after radiation in both submandibular (P = 0.037) and parotid groups (P = 0.006) compared to controls. Hyper-proliferation was seen only in parotid glands which was almost dose-dependent. Mean percentage MEC proliferation did not correlate with the clinical grading or recovery from oral mucositis (P = 0.47). CONCLUSIONS: Parotid glands are more sensitive to radiation compared to submandibular glands. Further research is needed to determine the role of MEC proliferative activity in response to radiation. PMID- 26668475 TI - Relationship between Severity of Periodontal Disease and Control of Diabetes (Glycated Hemoglobin) in Patients with Type 1 Diabetes Mellitus. AB - BACKGROUND: Both diabetes mellitus (DM) and periodontitis are chronic diseases affecting large number of the population worldwide. Changes in human behavior and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes in the world. This study was designed to evaluate the relationship between severity of periodontal disease and control of diabetes (glycated hemoglobin [HBA1c]) in patients with Type 1 DM in a hospital based study. MATERIALS AND METHODS: Fifty patients (n = 50) with Type 1 diabetes were enrolled in the study. They were divided into three groups based on the degree of glycemic control by measuring HbA1c levels as: "Good" (HBA1c <=7) Group A, fair (HBA1c = 7-8) Group B and poor (HBA1c >8) Group C. All enrolled patients underwent detailed history and dental checkup. Evaluation for periodontal disease was done by measuring dental plaque (plaque index), inflammation of gums (gingival index), probing pocket depth (PPD), and clinical attachment level. RESULTS: Type 1 diabetics with poor glycemic control had increased gingival inflammation (P < 0.05), more dental plaque (P < 0.05), increased PPDs (P < 0.05) and attachment loss (P < 0.05) as compared to those with fair and good glycemic control, respectively. CONCLUSION: Severity of periodontal disease increases with poor glycemic control in patients with Type 1 DM. PMID- 26668476 TI - Evaluation of Fracture Resistance of Endodontically Treated Teeth Filled with Gutta-Percha and Resilon Obturating Material: An In Vitro Study. AB - BACKGROUND: As per many studies endodontically treated teeth are widely considered to be more susceptible to fracture than vital teeth. Obturation strains and post placement have been a major cause of vertical root fracture. Present study was conducted to compare in vitro fracture resistance after filling with either Gutta-percha or Resilon by lateral condensation techniques in root canals. This study evaluated a new thermoplastic synthetic polymer based on polyester, which contains bioactive and radiopaque filler, Resilon performs every way as Gutta-percha except that it allows the bonding agent to attach to the resin core and the dentin wall thus forming a monoblock. MATERIALS AND METHODS: In the present study 90 freshly extracted single-rooted human mandibular premolar teeth endodontically treated, were cut at the cemento-enamel junction, and were randomly divided into three groups of 30 each as teeth of Group A (Control) received no obturation, Group B teeth were obturated using Gutta-percha/AH26, and Group C teeth were obturated using Resilon/Epiphany obturating kit. Each specimen were mounted in acrylic in a polyvinyl ring and then tested for fracture resistance with the help of an universal testing machine. A compressive force was applied until the root is fractured. The data were subjected to analysis of variance for comparing mean difference of fracture resistance among three groups. Multiple comparisons among these groups were carried out by non-parametric Kruskal-Wallis analysis. A p value of <0.0001 was considered a statistically significant difference. RESULTS: The results obtain after analysis showed no significant differences in the fracture resistance between the two tested groups of endodontic sealers. CONCLUSION: Within the limitation of the present in-vitro study, Resilon/Epiphany sealer performs better than Gutta-percha/AH 26 sealer with lateral condensation technique. PMID- 26668477 TI - The Effect of Two Soft Drinks on Bracket Bond Strength and on Intact and Sealed Enamel: An In Vitro Study. AB - BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the effect of two soft drinks, Coca-Cola and Mirinda orange on bracket bond strength, on adhesive remnant on teeth after debonding the bracket, and to observe by means of scanning electron microscope (SEM) the effect of these drinks on intact and sealed enamel. METHODS: 120 non-carious maxillary premolar teeth already extracted for Orthodontic purposes were taken and divided into three groups, i.e., Coca-Cola drink, Mirinda orange, and control (artificial saliva) group. Brackets were bonded using conventional methods. Teeth were kept in soft drinks for 15 days, for 15 min, 3 times a day, separated by intervals of 2 h. At other times, they were kept in artificial saliva. The samples, thus obtained were evaluated for shear bond strength using the universal testing machine and subsequently subjected for adhesive remnant index (ARI) scores. SEM study on all the three groups was done for evaluating enamel surface of the intact and sealed enamel. RESULTS: The lowest mean resistance to shearing forces was shown by Mirinda orange group (5.30 +/- 2.74 Mpa) followed by Coca-Cola group (6.24 +/- 1.59 Mpa) and highest resistance to shearing forces by control group (7.33 +/- 1.72 Mpa). The ARI scores revealed a cohesive failure in control samples and an adhesive failure in Mirinda and cola samples. SEM results showed areas of defect due to erosion caused by acidic soft drinks on intact and sealed enamel surface. CONCLUSION: Mirinda group showed the lowest resistance to shearing forces, followed by Coca-Cola group and with the highest resistance to shearing forces by the control group. There were significant differences between the control group and the study groups. Areas of defects, which were caused by erosion related to acidic soft drinks on the enamel surface around the adhesive, were seen. Areas of defects caused by Coca-Cola were more extensive when compared to Mirinda orange drink. PMID- 26668478 TI - Enamel Surface Evaluation after Removal of Orthodontic Composite Remnants by Intraoral Sandblasting Technique and Carbide Bur Technique: A Three-Dimensional Surface Profilometry and Scanning Electron Microscopic Study. AB - BACKGROUND: The purpose of this thesis is to present a practical and efficient clinical method of returning enamel to as near its original condition as possible following removal of bonded orthodontic attachments. The main objective of this study is to evaluate and compare the iatrogenic enamel damage caused by use of two different remnant removal techniques - sandblasting technique and carbide bur technique. MATERIALS AND METHODS: 40 extracted premolar teeth were selected as sample. Premolar brackets were bonded on these teeth with two different types of light cure adhesive composite resin. The remnants present on these samples after debonding the brackets were removed with two different types of remnant removal techniques namely - Carbide bur technique and sandblasting technique. Then these treated surfaces were studied under Scanning electron microscope and three dimensional profilometer for the damage caused to the enamel. Statistical analysis used Student's t-tests. RESULTS: The enamel surface structure after remnant removal with intraoral sandblasting is better than that after removal with a low-speed handpiece using tungsten carbide bur. CONCLUSION: Sandblasting can be an acceptable alternative to rotatory handpieces to restore the enamel surface to its near-original state and prevent permanent damage to the tooth. PMID- 26668479 TI - An Analysis of Correlation between Demand and Need for Orthodontic Treatment among Patients in Prince Sattam Bin Abdulaziz University Dental College Clinic, Kingdom of Saudi Arabia. AB - BACKGROUND: The objective of the study is to determine whether there is any correlation between demand and need for orthodontic treatment among patients in Sattam Bin Abdulaziz University (SAU) Dental College Clinic. This study also provides a baseline data on the demand and need for orthodontic treatment among a Saudi population, which is important for planning public orthodontic dental services in the Kingdom. MATERIALS AND METHODS: An epidemiological descriptive survey was conducted using two sets of questionnaire in the orthodontic clinic of Prince SAU, Al-Kharj among Saudi subjects with angle's Class I, Class II, and Class III malocclusions, between the ages of 10 and 30 years for a period of 6 months with purposive sampling method. RESULTS: Using Spearman's rank correlation coefficient a significant correlation (0.482) was observed in male and female patients respectively with orthodontic demand (2) and treatment need (1) at 0.05 level of significance. A significant correlation (0.326) was observed for the study subjects (both males and females) with orthodontic demand (4) and treatment need (1) at 0.05 level of significance. A significant correlation (0.325) was observed in male patients with orthodontic demand (4) and treatment need (5) at 0.05 level of significance. CONCLUSIONS: Patients with the higher orthodontic demand required high treatment needs and vice versa. PMID- 26668480 TI - Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex? AB - BACKGROUND: A pre-packaged mixture of areca nut, tobacco, slaked lime, catechu, and flavoring agents is popularly known as Gutkha. Aim of study is to analyze the addiction biology of Gutkha chewing and to assess efficacy of a cessation program based on nicotine replacement therapy (NRT). MATERIALS AND METHODS: Patterns of addiction of 400 Gutkha chewers were analyzed with a questionnaire-based survey. Urine cotinine levels of 60 subjects undergoing NRT were periodically estimated using gas chromatography. RESULTS: Mean urine cotinine levels of relapse and relapse-free cases were 5800.38 ug/g of creatine and 5622.16 ug/g of creatine. The difference was not found to be statistically significant. A 83.3% of the subjects associated their chewing habit with day to day activities. Overall relapse rate was found to be 79%. The most common reported reason for relapse was unacceptable taste and form of nicotine chewing gums. CONCLUSION: Repetitive coexistence in time of an indifferent act and the act of chewing Gutkha where, the act of chewing is almost always preceded by the indifferent act sets in a conditioned reflex. Gutkha addiction can be considered as a form of conditioned reflex, rather than actual craving for nicotine. PMID- 26668481 TI - Assessment of Systemic Inflammatory Markers in Patients with Aggressive Periodontitis. AB - BACKGROUND: "Aggressive periodontitis (AgP) is a destructive disease characterized by the following: The involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases.'' Chronic low-level bacteremia and systemic inflammatory response have been suggested as a pathogenic link between periodontal disease and systemic disease. The present study was aimed to assess the levels of systemic inflammatory markers in patients with AgP. METHODS: A sample of 50 systemically healthy patients comprised two groups, based on full mouth periodontal examination: Group I healthy individuals, includes 25 periodontally healthy subjects with fully functioning dentition. Group II includes 25 patients diagnosed clinically as AgP. Laboratory blood investigation included white blood cell (WBC) count, neutrophil count, lymphocyte count, and platelet count. Serum protein parameters included total protein (TP), albumin (ALB), and globulin (GLB). Periodontal clinical parameters including plaque index, gingival index, probing pocket depth, and clinical attachment level were recorded. RESULTS: Data analysis shows an increase in WBC, neutrophil, lymphocyte, and platelet count and a decrease in TP, ALB, and GLB in AgP patients when compared to healthy individuals. CONCLUSION: Results of the present study shows an increase in blood parameters and decrease in serum protein parameters in AgP. Hence, AgP could be considered as one of the risk factors associated with the cardiovascular diseases as assessed by changes in the level of systemic inflammatory markers observed. PMID- 26668482 TI - Knowledge, Attitudes and Practice about Research Ethics among Dental Faculty in the North India. AB - BACKGROUND: Research activities in dentistry are increased greatly in India during the recent decade, but there is limited of information about the knowledge and attitude of dental faculty for research ethics. To assess the knowledge and attitudes of dental faculty of North India regarding research ethics. MATERIALS AND METHODS: Through convenience sampling, a questionnaire was sent either via printed copies or E-mails to 1240 dental faculty, while protecting confidentiality and anonymity of all the participants. RESULTS: Our response rate was 76% (942). Majority (>90%) are aware of ethical committee but have poor knowledge (8-35%) about various ethical guidelines laid down at international level; however almost 20% believe that research ethics committees would delay research. A large number of researchers (78%) want some training in research ethics. There is fair knowledge about informed consent among researchers. CONCLUSIONS: We conclude that ethical norms should be strictly followed by giving due respect to confidentiality or privacy of research participants to achieve the goal of minimal risks and maximum benefits to patients and there is need of training to researchers and students to make them aware about various research principles. PMID- 26668483 TI - Palatal Rugae Patterns as a Bioindicator for Forensic Identification in Kodava and Tibetan Populations of India. AB - BACKGROUND: Palatal rugae are distinct to each individual and are highly specific to each individual as their fingerprints. Rugae pattern are specific to different racial groups making it convenient for population identification. Palatal rugae retain their shape throughout life and hence can be useful as an identification tool. The present study aimed at analyzing the differences in rugae pattern among Kodavas and Tibetan populations of Coorg, India and to examine if there was a difference in the rugae pattern between males and females within each group. MATERIALS AND METHODS: The study comprised of 30 participants between 18 and 30 years of age, equally distributed between genders from each group. Examination of maxillary cast after tracing the rugae patterns was carried out. Rugae pattern was classified as "straight," "wavy," "curved," "circular" and "unification." Statistical analysis was done using SPSS 16 software. Non-parametric Mann-Whitney test was used for pairwise comparison of two populations. Mann-Whitney two-tailed test was used to test the difference between males and females. RESULTS: Results showed that wavy pattern was highest for both the groups. Circular rugae were totally absent in both the groups. There was a significant difference between Kodavas (mean = 1.000) and Tibetans (mean = 0.13) for unification pattern (P = 0.001). CONCLUSION: Palatal rugae patterns can be used as a bioindicator for human identification. PMID- 26668484 TI - Partial Edentulism and its Association with Socio-Demographic Variables among Subjects Attending Dental Teaching Institutions, India. AB - BACKGROUND: Despite advances in preventive dentistry, edentulism is a major public health issues worldwide. Edentulism is an enervating and unrepairable condition and is described as the "final marker of disease burden for oral health." The objectives of the present study are to determine the relationship between socio-demographic variables and partial edentulism, and to evaluate the prevalence of various classes of partial edentulism by using Kennedy's classification. MATERIALS AND METHODS: Cross-sectional, descriptive study was conducted in an institution, on randomly selected individuals. The study group included adult patients who attended the outpatient Department of Prosthodontics during February-April 2015 formed the study participants. Data were collected by using a pre-formed pro-forma and Chi-square test was used to explore the relationship between two variables. RESULTS: A population comprised of 384 individuals between the age group of 18 and 35 years. Of these, 204 (53.12%) were males and 180 (46.88%) were females. Two hundred and eighty eight individuals were partially edentulous showing a prevalence rate of 75%. 51.04% of the study subjects were lost their teeth because of periodontol disease. 73.4% belonged to the upper middle class and 75.4% were in lower middle class in partially edentulous subjects. 45.8% had a fair oral hygiene status. Kennedy's class III was the most common type of partial edentulism in upper jaw and lower. CONCLUSION: The present study concluded that prevalence of partial edentulism among the study population was high. They need community-based oral health programs to increase the awareness and reduce the risk of tooth loss. PMID- 26668485 TI - Changes in Inflammatory Markers in Bacterial- and Nifedipine-Induced Gingival Inflammation. AB - BACKGROUND: Inflammatory gingival enlargement is a common observation in routine dental practice. Drugs like nifedipine, used for hypertension and Porphyromonas gingivalis infection-induced gingival enlargement is of a major concern. The current study aims to identify the inflammatory response of the gingival enlargement by measuring the major inflammatory markers fibrinogen and C-reactive protein (CRP). MATERIALS AND METHODS: Thirty-two patients with nifedipine-induced gingival enlargement, twelve with P. gingivalis infection, and seven with both drug and bacterial infection formed the test group and 16 age- and sex-matched healthy subjects formed the control. Gingival status was assessed, and the gingival index is noted. Fibrinogen and CRP were measured in venous blood. Results of the test and controls were compared using t-test and Pearson correlation. RESULTS: It was found that the changes in the inflammatory markers were statically significant in both fibrinogen levels and the CRP. The inflammation was more pronounced in subjects exposed to the drug and bacterial infection. The gingival index was found directly correlating with both the fibrinogen and the CRP levels. CONCLUSION: The quantitative estimation of both fibrinogen and CRP are good markers for the quantification of inflammation and hence evaluating the risk of coronary heart disease (CHD). Substituting the drug and reducing the bacterial load will help in improving the outcome of the treatment and thereby reducing the risk od CHD. PMID- 26668486 TI - Effect of Occlusal Scheme on the Pressure Distribution of Complete Denture Supporting Tissues: An In Vitro Study. AB - BACKGROUND: The complete denture teeth arrangement that gives maximum denture stability, comfort, esthetics, and function have been studied since several years. Many occlusal schemes have been advised in which the lingualized occlusion, balanced occlusion, and monoplane occlusion are advocated most popularly. The purpose of this study was to compare the pressure values on the supporting tissue using three diff erent posterior occlusal schemes: Balanced occlusion, lingualized occlusion, and monoplane occlusion in simulated dentures. MATERIALS AND METHODS: The simulators used in this study, composed of the maxillary, and mandibular clear heat cure acrylic resin edentulous models. Pressures on the supporting structure under the complete denture were measured using eight strain gauges placed on the model surface on the buccal and lingual slopes of the ridges on the molar and pre-molar region. Pressure on the supporting structure was measured and signals from the sensors were amplifi ed and recorded by the multi-channel electronic strain indicator. RESULTS: The mean pressure which was obtained at each measurement point was compared by one-way ANOVA test. CONCLUSION: Overall monoplane occlusion had lesser pressure values compared to completely balanced and lingualized occlusal scheme. Lingualized occlusal scheme was found to transfer stresses from working side to non-working side to stabilize the mandibular denture. PMID- 26668487 TI - Accidental Ingestion and Uneventful Retrieval of an Endodontic File in a 4 Year Old Child: A Case Report. AB - The majority of foreign body ingestions occur in the pediatric population, with a peak incidence between the ages of 6 months and 6 years. Safety during dental treatment of children cannot be overemphasized. Uncooperative, mentally and physically handicapped children are more prone to ingestion or aspiration of dental instruments than other populations. In any event, it is recommended that dental practitioners examine their instrument before use, as a safeguard against any slippage, breakage. Treatment with any endodontic device requires the use of proper isolation such as rubber dam. PMID- 26668488 TI - Prosthodontic Rehabilitation of Patients with Bell's Palsy: Our Experience. AB - Bell's palsy is an idiopathic unilateral lower motor neuron paresis or paralysis of the facial nerve of sudden onset. It involves loss of muscular control on the affected side of the face. This paper reports the prosthodontic management of patients with Bell's palsy and also describes a technique to stabilize the jaw movements in complete denture patients using interim dentures. A 65-year-old male edentulous patient and a 55-year-old female edentulous patient reported to the department of prosthodontics to get their missing teeth replaced. They both gave history of facial paralysis and were diagnosed for Bell's palsy. Interim training dentures with flat occlusal tables were fabricated first to correct and stabilize their mandibular movements. During initial 4 weeks, there was poor functioning of the interim dentures. Gradually by 8(th) week the patients started stabilizing the interim dentures and were functional. After observing the improvement when the patients had no pain and could stabilize and use the treatment dentures successfully, definitive complete dentures were fabricated. This case report presents a systematic approach to successively rehabilitate edentulous patients with Bell's palsy. PMID- 26668489 TI - Management of Class-II Furcation Complicated with Endodontic involvement using Two Different Regenerative Materials. AB - This paper presents a case series of furcation involved teeth complicated with endodontic involvement which were treated with periodontal, endodontic and restorative procedures using different bone regenerative materials like; (a) Calcium phosphosilicate bone substitute having bioactive glass 69% mixed with glycerin 19% and poly-ethylene 12% dispensed in a putty form; (b) hydroxyapatite 70% and beta-tricalcium phosphate 30% dispensed in granular form. All the cases were randomly selected having Grade II furcation defect with primary or secondary endodontic involvement. All cases were under observation for a period of 9 months. Measurements at 9 months post-surgery demonstrated that dental putty as bone graft substitute which was in combination of bioactive glass mixed with glycerine and polyethylene glycol showed better result as compared granular bone graft which was in combination of hydroxyapatite and beta-tricalcium phosphate. PMID- 26668490 TI - Exposed Dental Implant? Local Autograft A Saviour! AB - Implant exposure due to faulty placement, posses as the most common reason for implant failure. The implant placed too close to buccal or lingual cortex have lead to such failure on numerous occasions. Also, anatomic variations like the thin buccolingual width of alveolar ridge predispose exposure of the implant. 25 year-old female patient had undergone surgical placement of implants in mandibular anterior region 2 months back in the private dental clinic. The clinician noted Grade I mobility in one of the implants placed. The case was referred to the author. Thin overlying gingiva depicted an entire buccal aspect of the implant, which suggested more than 90 % loss of buccal cortex. According to literature and review of similar case reports, the only way suggested was to surgically remove the implant and wait for 12-24 months for the bone to heal for subsequent placement. Rather than the removal of implants as suggested, the author followed a naval approach of reinforcing buccal cortex using an autogenous cortical block from mandibular symphysis. The reinforcement surgery had certainly saved patients time, money and most importantly limits a crucial period of edentulism, which may be enforced on a patient in case the implant was removed. PMID- 26668491 TI - Gummy Smile Correction with Diode Laser: Two Case Reports. AB - Beautification of smiles is becoming an everyday requirement in dental practice. Apart from teeth, gingiva also plays an important role in smile esthetics. Excessive visualization of gingiva is a common complaint among patients seeking esthetic treatment. A wide variety of procedures are available for correction of excessive gum display based on the cause of the condition. Soft tissue diode laser contouring of gingiva is a common procedure that can be undertaken in a routine dental setting with excellent patient satisfaction and minimal post operative sequale. Two cases of esthetic crown lengthening with diode laser 810 nm are presented here. PMID- 26668492 TI - Recording Myocentric Relation in a Partially Edentulous Patient: A Case Report. AB - The masticatory system constitutes four closely interrelated components: Teeth, muscles, nerves, and temporomandibular joints (TMJ). The stable and physiologic rest position of the TMJ is based on the muscle guidance (mainly masticatory, and partially facial), neurally determined and controlled occlusion, integrated together with its peripheral proprioceptors and relax mechanism of the central nervous system. Oral rehabilitation procedures should emphasize on a holistic approach to establish a physiologic relationship of the lower jaw to the base of the cranium resulting in a neuromuscular rest position. This position then would support an occlusion for the stability of the TMJ, the masticatory muscles of the orofacial region and the teeth along with their supporting periodontium. Such a holistic approach becomes more important in cases where the patient not only requires oral rehabilitation but also presents with related TMJ problems. This is a case report where an attempt is made to rehabilitate a patient in a neuromuscular rest position by establishing a myocentric relation. PMID- 26668493 TI - Transposition/Fusion: A Clinician's Dilemma and Challenge - 12 Months Follow-up. AB - Fusion or syndontia is a sequele of the union of two normal and separated tooth buds. Transposition refers to the interchange in the position of two permanent teeth within the same quadrant in the oral cavity. The simultaneous incidence of both these entities is a rare concurrence and warrants endodontic and surgical soft tissue correction. The following manuscript describes a case report of this rare combination and its multidisciplinary management for functional and esthetic correction. PMID- 26668494 TI - Immediate Implant Placement in Anterior Aesthetic Region and Assessment using Cone-Beam Computed Tomography Scan Technology. AB - The esthetics and functional integrity of the periodontal tissues may be compromised by the dental loss. Dental implants have become an additional tool in the armamentarium of treatment options to offer the patient for the replacement of a missing tooth or teeth. Diagnosis and treatment planning is the key factors in achieving the successful outcome after placing and restoring implants placed immediately after tooth extraction. The introduction of cone-beam computed tomography (CBCT) for the maxillofacial region provides opportunities for dental practitioners to request multiplanar imaging. This case report demonstrates the use of CBCT scan technology in immediate implant placement in the maxillary anterior teeth region. PMID- 26668495 TI - Botox Therapy in Dentistry: A Review. AB - There are many medical and dental conditions which do not have complete treatment modalities in conventional ways. The botulinum toxin can be used as an alternative treatment modality working through chemo denervation method in many medical and dental conditions. An internet research was done for botulinum toxin used in dentistry and all articles and studies were selected, articles related to dentistry were extracted and summarized. This article explains the basic of botulinum toxin and some of its uses in dentistry. In next parts, the extensive details of its use in dentistry will be dealt with. PMID- 26668496 TI - Prosthodontic Management in Conjunction with Speech Therapy in Cleft Lip and Palate: A Review and Case Report. AB - Cleft lip and palate (CLP), a congenital disturbance needs a lot of attention with respect to its rehabilitation as a person suffering from this defect can lead a normal life given with the right type of treatment at the right time. However, if a patient cannot get surgical treatment at the appropriate time either due to availability or economic constraints, it is still possible to improve their social and psychological well-being with prosthodontic rehabilitation. The literature search was carried out through PubMed and Google scholar and manual search. The articles related to prosthodontic treatment in congestion with speech therapy and some articles on psychological assessment were considered The available prosthodontic treatment options for improvement of speech is discussed and highlighted the importance of prosthetic management of such patients along with a speech therapist. Also, a review of the available prosthetic treatment options is discussed in detail. Finally, a case report of a CLP patient treated prosthodontically with the assistance of speech pathologist is presented. PMID- 26668497 TI - Necroptosis: Changing Trends in Cell Biology and Cancer. PMID- 26668498 TI - Interval colorectal carcinoma: An unsolved debate. AB - Colorectal carcinoma (CRC), as the third most common new cancer diagnosis, poses a significant health risk to the population. Interval CRCs are those that appear after a negative screening test or examination. The development of interval CRCs has been shown to be multifactorial: location of exam-academic institution versus community hospital, experience of the endoscopist, quality of the procedure, age of the patient, flat versus polypoid neoplasia, genetics, hereditary gastrointestinal neoplasia, and most significantly missed or incompletely excised lesions. The rate of interval CRCs has decreased in the last decade, which has been ascribed to an increased understanding of interval disease and technological advances in the screening of high risk individuals. In this article, we aim to review the literature with regard to the multifactorial nature of interval CRCs and provide the most recent developments regarding this important gastrointestinal entity. PMID- 26668500 TI - Fluid management in living donor hepatectomy: Recent issues and perspectives. AB - The importance of the safety of healthy living liver donors is widely recognized during donor hepatectomy which is associated with blood loss, transfusion, and subsequent post-operative morbidity. Although the low central venous pressure (CVP) technique can still be effective, it may not be advantageous concerning the safety of healthy donors undergoing hepatectomy. Emerging evidence suggests that stroke volume variation (SVV), a simple and useful index for fluid responsiveness and preload status in various clinical situations, can be applied as a guide for fluid management to reduce blood loss during living donor hepatectomy. Synthetic colloid solutions are also associated with serious adverse events such as the use of renal replacement therapy and transfusion in critically ill or septic patients. However, it is uncertain whether the intra-operative use of colloid solution is associated with similarly adverse effects in patients undergoing living donor hepatectomy. In this review article we discuss the recent issues regarding the low CVP technique and the high SVV method, i.e., maintaining 10% 20% of SVV, for fluid management in order to reduce blood loss during living donor hepatectomy. In addition, we briefly discuss the effects of intra-operative colloid or crystalloid administration for surgical rather than septic or critically ill patients. PMID- 26668499 TI - Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. AB - The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context. PMID- 26668501 TI - Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice. AB - AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSS-induced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage. CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation. PMID- 26668502 TI - New drug delivery system for liver sinusoidal endothelial cells for ischemia reperfusion injury. AB - AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid (HA) and sphingosine 1 phophate. METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate (S1P), and HA-S1P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase (ALT), histological findings, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and transmission electron microscopy (TEM). We also investigated the expression of proteins associated with apoptosis, hepatoprotection, and S1P accumulation. RESULTS: S1P accumulated in the HA-S1P group livers more than S1P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1P group. TEM revealed that the liver sinusoidal endothelial cell (LSEC) lining was preserved in the HA-S1P group. Moreover, the HA-S1P group showed a greater increase in the HO-1 protein levels compared to the S1P group. CONCLUSION: Our results suggest that HA-S1P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1P is an effective agent for hepatic ischemia/reperfusion injury. PMID- 26668503 TI - Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease. AB - AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-delta agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. METHODS: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-delta agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW. RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1beta in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1beta. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-alpha. CONCLUSION: PPAR-delta agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-delta agonist may have therapeutic implication for NAFLD. PMID- 26668504 TI - Biliary tract external drainage protects against intestinal barrier injury in hemorrhagic shock rats. AB - AIM: To investigate the effects of biliary tract external drainage (BTED) on intestinal barrier injury in rats with hemorrhagic shock (HS). METHODS: BTED was performed via cannula insertion into the bile duct of rats. HS was induced by drawing blood from the femoral artery at a rate of 1 mL/min until a mean arterial pressure (MAP) of 40 +/- 5 mmHg was achieved. That MAP was maintained for 60 min. A total of 99 Sprague-Dawley rats were randomized into a sham group, an HS group and an HS + BTED group. Nine rats in the sham group were sacrificed 0.5 h after surgery. Nine rats in each of the HS and HS + BTED groups were sacrificed 0.5 h, 1 h, 2 h, 4 h and 6 h after resuscitation. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and lipopolysaccharide (LPS) levels were analyzed using enzyme-linked immunosorbent assay. Plasma D-lactate levels were analyzed using colorimetry. The expression levels of occludin and claudin-1 in the ileum were analyzed using Western blot and immunohistochemistry. Histology of the ileum was evaluated by hematoxylin and eosin staining. RESULTS: Plasma TNF alpha levels in the HS + BTED group decreased significantly compared with the HS group at 1 h and 6 h after resuscitation (P < 0.05). Plasma IL-6 levels in the HS + BTED group decreased significantly compared with the HS group at 0.5 h, 1 h and 2 h after resuscitation (P < 0.05). Plasma D-lactate and LPS levels in the HS + BTED group decreased significantly compared with the HS group at 6 h after resuscitation (P < 0.05). The expression levels of occludin in the HS + BTED group increased significantly compared with the HS group at 4 h and 6 h after resuscitation (P < 0.05). The expression levels of claudin-1 in the HS + BTED group increased significantly compared with the HS group at 6 h after resuscitation (P < 0.05). Phenomena of putrescence and desquamation of epithelial cells in the ileal mucosa were attenuated in the HS + BTED group. Ileal histopathologic scores in the HS + BTED group decreased significantly compared with the HS group at 2 h, 4 h and 6 h after resuscitation (P < 0.05). CONCLUSION: BTED protects against intestinal barrier injury in HS rats. PMID- 26668505 TI - Chemosensitization of HepG2 cells by suppression of NF-kappaB/p65 gene transcription with specific-siRNA. AB - AIM: To investigate small interfering RNA (siRNA)-mediated inhibition of nuclear factor-kappa B (NF-kappaB) activation and multidrug-resistant (MDR) phenotype formation in human HepG2 cells. METHODS: Total RNA was extracted from human HepG2 or LO2 cells. NF-kappaB/p65 mRNA was amplified by nested reverse transcription polymerase chain reaction and confirmed by sequencing. NF-kappaB/p65 was analyzed by immunohistochemistry. Specific-siRNA was transfected to HepG2 cells to knock down NF-kappaB/p65 expression. The effects on cell proliferation, survival, and apoptosis were assessed, and the level of NF-kappaB/p65 or P-glycoprotein (P-gp) was quantitatively analyzed by enzyme-linked immunosorbent assay. RESULTS: HepG2 cells express NF-kappaB/p65 and express relatively less phosphorylated p65 (P p65) and little P-gp. After treatment of HepG2 cells with different doses of doxorubicin, the expression of NF-kappaB/p65, P-p65, and especially P-gp were dose-dependently upregulated. After HepG2 cells were transfected with NF kappaB/p65 siRNA (100 nmol/L), the expression of NF-kappaB/p65, P-p65, and P-gp were downregulated significantly and dose-dependently. The viability of HepG2 cells was decreased to 23% in the combination NF-kappaB/p65 siRNA (100 nmol/L) and doxorubicin (0.5 MUmol/L) group and 47% in the doxorubicin (0.5 MUmol/L) group (t = 7.043, P < 0.001). CONCLUSION: Knockdown of NF-kappaB/p65 with siRNA is an effective strategy for inhibiting HepG2 cell growth by downregulating P-gp expression associated chemosensitization and apoptosis induction. PMID- 26668507 TI - Nutritional care in hospitalized patients with chronic liver disease. AB - AIM: To evaluate the practice of nutritional assessment and management of hospitalised patients with cirrhosis and the impact of malnutrition on their clinical outcome. METHODS: This was a retrospective cohort study on patients with liver cirrhosis consecutively admitted to the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital over 24 mo. Details were gathered related to the patients' demographics, disease severity, nutritional status and assessment, biochemistry and clinical outcomes. Nutritional status was assessed by a dietician and determined by subjective global assessment. Estimated energy and protein requirements were calculated by Simple Ratio Method. Intake was estimated from dietary history and/or food charts, and represented as a percentage of estimated daily requirements. Median duration of follow up was 14.9 (0-41.4) mo. RESULTS: Of the 231 cirrhotic patients (167 male, age: 56.3 +/- 0.9 years, 9% Child-Pugh A, 42% Child-Pugh B and 49% Child-Pugh C), 131 (57%) had formal nutritional assessment during their admission and 74 (56%) were judged to have malnutrition. In-hospital caloric (15.6 +/- 1.2 kcal/kg vs 23.7 +/- 2.3 kcal/kg, P = 0.0003) and protein intake (0.65 +/- 0.06 g/kg vs 1.01 +/- 0.07 g/kg, P = 0.0003) was significantly reduced in patients with malnutrition. Of the malnourished cohort, 12 (16%) received enteral nutrition during hospitalisation and only 6 (8%) received ongoing dietetic review and assessment following discharge from hospital. The overall mortality was 51%, and was higher in patients with malnutrition compared to those without (HR = 5.29, 95%CI: 2.31 12.1; P < 0.001). CONCLUSION: Malnutrition is common in hospitalised patients with cirrhosis and is associated with higher mortality. Formal nutritional assessment, however, is inadequate. This highlights the need for meticulous nutritional evaluation and management in these patients. PMID- 26668506 TI - Heat shock pretreatment improves stem cell repair following ischemia-reperfusion injury via autophagy. AB - AIM: To investigate whether heat shock pretreatment (HSP) improves mesenchymal stem cell (MSC) repair via autophagy following hepatic ischemia-reperfusion injury (HIRI). METHODS: Apoptosis of MSCs was induced by 250 mM hydrogen peroxide (H2O2) for 6 h. HSP was carried out using a 42 degrees C water bath for 1, 2 or 3 h. Apoptosis of MSCs was analyzed by flow cytometry, and Western blot was used to detect Bcl-2, Bax and cytochrome C expression. Autophagy of MSCs was analyzed by flow cytometry and transmission electron microscopy, and the expression of beclin I and LC3-II was detected by Western blot. MSCs were labeled in vivo with the fluorescent dye, CM-Dil, and subsequently transplanted into the portal veins of rats that had undergone HIRI. Liver levels of proliferating cell nuclear antigen (PCNA) were quantified by fluorescent microscopy. Serum aminotransferase activity and the extent of HIRI were also assessed at each time point. RESULTS: HSP for 2 h reduced apoptosis of MSCs induced by H2O2 as seen by a decrease in apoptotic rate, a decrease in Bax and cytochrome C expression and an increase in Bcl-2 expression (P < 0.001). In addition, HSP for 2 h induced autophagy of MSCs exposed to H2O2 as shown by an increase in acidic vesicular organelle-positive cells, beclin 1 and LC3-II expression, and autophagosome formation (P < 0.05). Treatment with 3-methyladenine attenuated HSP-induced autophagy and abolished the protective effects of HSP on the apoptosis of MSCs. Rapamycin failed to have additional effects on either autophagy or apoptosis compared with HSP alone. The phosphorylation of p38MAPK was significantly elevated and the phosphorylation of mTOR was downregulated in heat shock pretreated MSCs. Treatment with the p38MAPK inhibitor, SB203580, reduced HSP-induced autophagy in MSCs. In vivo studies showed that the transplantation of HSP-MSCs resulted in lower serum aminotransferase levels, lower Suzuki scores, improved histopathology and an increase in PCNA-positive cells (P < 0.05). CONCLUSION: HSP effectively induces autophagy following exposure to H2O2 via the p38MAPK/mTOR pathway, which leads to enhanced MSC survival and improved MSC repair following HIRI in rats. PMID- 26668508 TI - Laparoscopic vs open partial colectomy in elderly patients: Insights from the American College of Surgeons - National Surgical Quality Improvement Program database. AB - AIM: To compare the outcomes between the laparoscopic and open approaches for partial colectomy in elderly patients aged 65 years and over using the American College of Surgeons - National Surgical Quality Improvement Program (ACS NSQIP) database. METHODS: The ACS NSQIP database for the years 2005-2011 was queried for all patients 65 years and above who underwent partial colectomy. 1:1 propensity score matching using the nearest- neighbor method was performed to ensure both groups had similar pre-operative comorbidities. Outcomes including post-operative complications, length of stay and mortality were compared between the laparoscopic and open groups. chi(2) and Fisher's exact test were used for discrete variables and Student's t-test for continuous variables. P < 0.05 was considered significant and odds ratios with 95%CI were reported when applicable. RESULTS: The total number of patients in the ACS NSQIP database of the years 2005 2011 was 1777035. We identified 27604 elderly patients who underwent partial colectomy with complete data sets. 12009 (43%) of the cases were done laparoscopically and 15595 (57%) were done with open. After propensity score matching, there were 11008 patients each in the laparoscopic (LC) and open colectomy (OC) cohorts. The laparoscopic approach had lower post-operative complications (LC 15.2%, OC 23.8%, P < 0.001), shorter length of stay (LC 6.61 d, OC 9.62 d, P < 0.001) and lower mortality (LC 1.6%, OC 2.9%, P < 0.001). CONCLUSION: Even after propensity score matching, elderly patients in the ACS NSQIP database having a laparoscopic partial colectomy had better outcomes than those having open colectomies. In the absence of specific contraindications, elderly patients requiring a partial colectomy should be offered the laparoscopic approach. PMID- 26668509 TI - Clinicopathological characteristics of clinical early gastric cancer in the upper third stomach. AB - AIM: To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions. METHODS: A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach (U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography (CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower third stomach (ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth. RESULTS: Patients in the U group were older (P = 0.029), had a higher ratio of males to females (P = 0.015), and had more histologically differentiated tumors (P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients (8.3%), and was more frequent in the U group than in the ML group (16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group (P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors (P = 0.094) and in those larger than 4 cm (P = 0.024). The median follow-up period after surgery was 56 mo (range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group (P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study. CONCLUSION: Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors. PMID- 26668511 TI - Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma for hepatolithiasis. AB - AIM: To evaluate the long-term outcomes of Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS) and risk factors for recurrence in hepatolithiasis. METHODS: From March 1993 to December 2012, 202 consecutive patients with hepatolithiasis underwent OSPCHS at our department. The Oddi sphincter preserved procedure consisted of common hepatic duct exploration, stone extraction, hilar bile duct plasty, establishment of subcutaneous stoma to the bile duct. Patients with recurrent stones can undergo stone extraction and/or biliary drainage via the subcutaneous stoma which can be incised under local anesthesia. The long-term results were reviewed. Cox regression model was employed to analyze the risk factors for stone recurrence. RESULTS: Ninety-seven (48.0%) OSPCHS patients underwent hepatic resection concomitantly. The rate of surgical complications was 10.4%. There was no perioperative death. The immediate stone clearance rate was 72.8%. Postoperative cholangioscopic lithotomy raised the clearance rate to 97.0%. With a median follow-up period of 78.5 mo (range: 2 233 mo), 24.8% of patients had recurrent stones, 2.5% had late development of cholangiocarcinoma, and the mortality rate was 5.4%. Removal of recurrent stones and/or drainage of inflammatory bile via subcutaneous stoma were conducted in 44 (21.8%) patients. The clearance rate of recurrent stones was 84.0% after subsequent choledochoscopic lithotripsy via subcutaneous stoma. Cox regression analysis showed that residual stone was an independent prognostic factor for stone recurrence. CONCLUSION: In selected patients with hepatolithiasis, OSPCHS achieves excellent long-term outcomes, and residual stone is an independent prognostic factor for stone recurrence. PMID- 26668510 TI - Innovative technique of needlescopic grasper-assisted single-incision laparoscopic common bile duct exploration: A comparative study. AB - AIM: To investigate the safety and feasibility of needlescopic grasper-assisted single-incision laparoscopic common bile duct exploration (nSIL-CBDE) by comparing the surgical outcomes of this technique with those of conventional laparoscopic CBDE (CL-CBDE). METHODS: We retrospectively analyzed the clinical data of patients who underwent CL-CBDE or nSIL-CBDE for the treatment of common bile duct (CBD) stones between January 2000 and December 2014. For performing nSIL-CBDE, a needlescopic grasper was also inserted through a direct puncture below the right subcostal line after introducing a single-port through the umbilicus. The needlescopic grasper helped obtain the critical view of safety by retracting the gallbladder laterally and by preventing crossing or conflict between laparoscopic instruments. The gallbladder was then partially dissected from the liver bed and used for retraction. CBD stones were usually extracted through a longitudinal supraduodenal choledochotomy, mostly using flushing a copious amount of normal saline through a ureteral catheter. Afterward, for the certification of CBD clearance, CBDE was performed mostly using a flexible choledochoscope. The choledochotomy site was primarily closed without using a T tube, and simultaneous cholecystectomies were performed. RESULTS: During the study period, 40 patients underwent laparoscopic CBDE. Of these patients, 20 underwent CL-CBDE and 20 underwent nSIL-CBDE. The operative time for nSIL-CBDE was significantly longer than that for CL-CBDE (238 +/- 76 min vs 192 +/- 39 min, P = 0.007). The stone clearance rate was 100% (40/40) in both groups. Postoperatively, the nSIL-CBDE group required less intravenous analgesic (pethidine) (46.5 +/- 63.5 mg/kg vs 92.5 +/- 120.1 mg/kg, P = 0.010) and had a shorter hospital stay than the CL-CBDE group (3.8 +/- 2.0 d vs 5.1 +/- 1.7 d, P = 0.010). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSION: The results of this study suggest that nSIL-CBDE could be safe and feasible while improving cosmetic outcomes when performed by surgeons trained in conventional laparoscopic techniques. PMID- 26668512 TI - Updated experiences with minimally invasive McKeown esophagectomy for esophageal cancer. AB - AIM: To update our experiences with minimally invasive McKeown esophagectomy for esophageal cancer. METHODS: We retrospectively reviewed the medical records of 445 consecutive patients who underwent minimally invasive McKeown esophagectomy between January 2009 and July 2015 at the Cancer Hospital of Chinese Academy of Medical Sciences and used 103 patients who underwent open McKeown esophagectomy in the same period as controls. Among 375 patients who underwent total minimally invasive McKeown esophagectomy, 180 in the early period were chosen for the study of learning curve of total minimally invasive McKeown esophagectomy. These 180 minimally invasive McKeown esophagectomies performed by five surgeons were divided into three groups according to time sequence as group 1 (n = 60), group 2 (n = 60) and group 3 (n = 60). RESULTS: Patients who underwent total minimally invasive McKeown esophagectomy had significantly less intraoperative blood loss than patients who underwent hybrid minimally invasive McKeown esophagectomy or open McKeown esophagectomy (100 mL vs 300 mL vs 200 mL, P = 0.001). However, there were no significant differences in operation time, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between total minimally invasive McKeown esophagectomy, hybrid minimally invasive McKeown esophagectomy and open McKeown esophagectomy groups. There were no significant differences in 5-year survival between these three groups (60.5% vs 47.9% vs 35.6%, P = 0.735). Patients in group 1 had significantly longer duration of operation than those in groups 2 and 3. There were no significant differences in intraoperative blood loss, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between groups 1, 2 and 3. CONCLUSION: Total minimally invasive McKeown esophagectomy was associated with reduced intraoperative blood loss and comparable short term and long term survival compared with hybrid minimally invasive McKeown esophagectomy or open Mckeown esophagectomy. At least 12 cases are needed to master total minimally invasive McKeown esophagectomy in a high volume center. PMID- 26668513 TI - Comparison of Stretta procedure and toupet fundoplication for gastroesophageal reflux disease-related extra-esophageal symptoms. AB - AIM: To compare the outcomes between the Stretta procedure and laparoscopic toupet fundoplication (LTF) in patients with gastroesophageal reflux disease (GERD)-related extra-esophageal symptoms. METHODS: From January 2011 to February 2012, a total of 98 patients diagnosed with GERD-related extra-esophageal symptoms who met the inclusion criteria were enrolled in this study. All patients who either underwent the Stretta procedure or LTF treatment have now completed the 3-year follow-up. Primary outcome measures, including frequency and severity of extra-esophageal symptoms, proton pump inhibitor (PPI) use, satisfaction, and postoperative complications, were assessed. The results of the Stretta procedure and LTF therapy were analyzed and compared. RESULTS: There were 47 patients in the Stretta group and 51 patients in the LTF group. Ninety patients were available at the 3-year follow-up. The total of the frequency and severity scores for every symptom improved in both groups (P < 0.05). Improvement in symptom scores of cough, sputum, and wheezing did not achieve statistical significance between the two groups (P > 0.05). However, the score for globus hysterics was different between the Stretta group and the LTF group (4.9 +/- 2.24 vs 3.2 +/- 2.63, P < 0.05). After the Stretta procedure and LTF treatment, 29 and 33 patients in each group achieved PPI therapy independence (61.7% vs 64.7%, P = 0.835). The patients in the LTF group were more satisfied with their quality of life than those in the Stretta procedure group (P < 0.05). Most complications resolved without intervention within two weeks; however, two patients in the LTF group still suffered from severe dysphagia 2 wk after the operation, and it improved after bougie dilation treatment in both patients. CONCLUSION: The Stretta procedure and LTF were both safe and effective for the control of GERD related extra-esophageal symptoms and the reduction of PPI use. PMID- 26668514 TI - Effect of posture on (13)C-urea breath test in partial gastrectomy patients. AB - AIM: To investigate whether posture affects the accuracy of (13)C-urea breath test ((13)C-UBT) for Helicobacter pylori (H. pylori) detection in partial gastrectomy patients. METHODS: We studied 156 consecutive residual stomach patients, including 76 with H. pylori infection (infection group) and 80 without H. pylori infection (control group). H. pylori infection was confirmed if both the rapid urease test and histology were positive during gastroscopy. The two groups were divided into four subgroups according to patients' posture during the (13)C-UBT: subgroup A, sitting position; subgroup B, supine position; subgroup C, right lateral recumbent position; and subgroup D, left lateral recumbent position. Each subject underwent the following modified (13)C-UBT: 75 mg of (13)C urea (powder) in 100 mL of citric acid solution was administered, and a mouth wash was performed immediately; breath samples were then collected at baseline and at 5-min intervals up to 30 min while the position was maintained. Seven breath samples were collected for each subject. The cutoff value was 2.00/00. RESULTS: The mean delta over baseline (DOB) values in the subgroups of the infection group were similar at 5 min (P > 0.05) and significantly higher than those in the corresponding control subgroups at all time points (P < 0.01). In the infection group, the mean DOB values in subgroup A were higher than those in other subgroups within 10 min and peaked at the 10-min point (12.40/00 +/- 2.40/00). The values in subgroups B and C both reached their peaks at 15 min (B, 13.90/00 +/- 1.50/00; C, 12.20/00 +/- 1.70/00) and then decreased gradually until the 30-min point. In subgroup D, the value peaked at 20 min (14.70/00 +/- 1.70/00). Significant differences were found between the values in subgroups D and B at both 25 min (t = 2.093, P = 0.043) and 30 min (t = 2.141, P = 0.039). At 30 min, the value in subgroup D was also significantly different from those in subgroups A and C (D vs C: t = 6.325, P = 0.000; D vs A: t = 5.912, P = 0.000). The mean DOB values of subjects with Billroth I anastomosis were higher than those of subjects with Billroth II anastomosis irrespectively of the detection time and posture (P > 0.05). CONCLUSION: Utilization of the left lateral recumbent position during the procedure and when collecting the last breath sample may improve the diagnostic accuracy of the (13)C-UBT in partial gastrectomy patients. PMID- 26668516 TI - Hybrid therapy for Helicobacter pylori infection: A systemic review and meta analysis. AB - AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using meta-analysis. METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in PubMed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords (all fields and/or MeSH): ("Helicobacter pylori" or "H. pylori") and ("hybrid therapy" or "sequential-concomitant therapy"). Meta-analyses were performed with Cochrane Review Manager 5.1. The random effect model proposed by DerSimonian and Laird and the Mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies. RESULTS: Eight studies (2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat (ITT) and per protocol analyses were 88.5% (n = 1207; range: 80.0% to 97.4%) and 93.3% (n = 1109; range: 85.7% to 99.1%), respectively. Meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy (relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations (95%CI: 1.01-1.18) and was only less effective in one, Italian population (95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy (95%CI: 0.93-1.02). No head to-head comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy (95.5% vs 88.6% ITT; P = 0.011). CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance. PMID- 26668518 TI - Minimally invasive surgery for superior mesenteric artery syndrome: A case report. AB - Superior mesenteric artery (SMA) syndrome is defined as a compression of the third portion of the duodenum by the abdominal aorta and the overlying SMA. SMA syndrome associated with anorexia nervosa has been recognized, mainly among young female patients. The excessive weight loss owing to the eating disorder sometimes results in a reduced aorto-mesenteric angle and causes duodenal obstruction. Conservative treatment, including psychiatric and nutritional management, is recommended as initial therapy. If conservative treatment fails, surgery is often required. Currently, traditional open bypass surgery has been replaced by laparoscopic duodenojejunostomy as a curative surgical approach. However, single incision laparoscopic approach is rarely performed. A 20-year-old female patient with a diagnosis of anorexia nervosa and SMA syndrome was prepared for surgery after failed conservative management. As the patient had body image concerns, a single incision laparoscopic duodenojejunostomy was performed to achieve minimal scarring. As a result, good perioperative outcomes and cosmetic results were achieved. We show the first case of a young patient with SMA syndrome who was successfully treated by single incision laparoscopic duodenojejunostomy. This minimal invasive surgery would be beneficial for other patients with SMA syndrome associated with anorexia nervosa, in terms of both surgical and cosmetic outcomes. PMID- 26668517 TI - First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy. AB - We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN gamma. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. PMID- 26668519 TI - Endoscopic fibrin sealant closure of duodenal perforation after endoscopic retrograde cholangiopancreatography. AB - Traditionally, perivaterian duodenal perforation can be managed conservatively or surgically. If a large volume of leakage results in fluid collection in the retroperitoneum, surgery may be necessary. Our case met the surgical indication for perivaterian duodenal perforation after endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and endoscopic papillary balloon dilatation. The patient developed a retroperitoneal abscess after the procedures, and a perivaterian perforation was suggested on computed tomography (CT). CT-guided abscess drainage was performed immediately. We unsuccessfully attempted to close the perforation with hemoclips initially. Subsequently, we used fibrin sealant (Tisseel) injection to occlude the perforation. Fibrin sealant injections have been previously used during endoscopy for wound closure and fistula repair. Based on our report, fibrin sealant injection can be considered as an alternative method for the treatment of ERCP-related type II perforations. PMID- 26668520 TI - Coexistence of hepatoma with mantle cell lymphoma in a hepatitis B carrier. AB - The coexistence of hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma (NHL) in the liver is rare. Reports show that these patients have cirrhotic livers or hepatitis virus infections before they develop HCC and NHL. We present a patient with hepatitis B virus infection who was transferred to our hospital with a newly detected liver mass; abdominal computed tomography examination showed one hypodense mass of 7 cm in diameter and multiple mesenteric and mediastinal lymph nodes. A liver tumor biopsy showed a hepatoma, and the pathologic findings from an inguinal lymph node excision showed mantle cell lymphoma. An immunohistochemical stain confirmed that the atypical lymphoid cells within the HCC were positive for the CD20, CD5 and cyclin D1 antigens. Taking these findings into account, the hepatic tumor was determined to be a HCC infiltrated by mantle cell lymphoma. PMID- 26668521 TI - Percutaneous peritoneal drainage in isolated neonatal gastric perforation. AB - A comment on the article by He et al, "Idiopathic neonatal pneumoperitoneum with favorable outcome: A case report and review", published on World Journal of Gastroenterology that reported a case of idiopathic neonatal pneumoperitoneum, possibly due to gastric perforation, with a favorable outcome without surgical intervention. PMID- 26668522 TI - Bile duct ischemia developing after reconstruction of the hepatic artery during the Whipple operation. AB - A pancreaticoduodenectomy is a surgical procedure with a high morbidity and mortality rate. The injury of the hepatic artery may occasionally lead to intraoperative bleeding. Repair of the injured hepatic artery is of great importance in terms of maintaining the vascular supply of the liver. We report a case with an injury of the hepatic artery that was successfully reconstructed with the gastroduodenal artery and then developed a biliary leak due to bile duct ischemia at an early stage. A 33-year-old women complaining of right upper quadrant pain was found to have a solid pseudopapillary tumor of the pancreas. She underwent an immediate pancreaticoduodenectomy, and her hepatic artery was injured during the operation. The arterial ends were sutured with primary anastomosis, because they could be aligned without any tension. The biliary leak occurred on postoperative day 2. We detected bile duct ischemia and reanastomosed the artery. The patient was discharged on postoperative day 8. Surgeons should be prepared for anomalies of the peripancreatic vascular structures during pancreaticoduodenectomy. Computed tomography angiography should be considered to reveal these anomalies before the surgery. Insufficiency of the biliodigestive anastomosis due to bile duct ischemia in the postoperative period should be kept in mind, even in cases of successful repair. PMID- 26668515 TI - Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review. AB - AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin , prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association. PMID- 26668523 TI - Gallbladder paraganglioma. AB - Gallbladder paraganglioma is a very rare tumor, and only a few cases have been reported. Most of these cases were asymptomatic and found incidentally during operation. Our case involved a 57-year-old female patient complaining of intermittent right upper quadrant pain. Preoperative imaging demonstrated a mass in the neck of the gallbladder. Laparoscopic cholecystectomy was performed, and a frozen section of the gallbladder demonstrated a benign mass. The postoperative pathologic examination reported gallbladder paraganglioma and chronic cholecystitis. Immunohistochemically, the chief cells and sustentacular cells showed diffuse positivity with vimentin, synaptophysin, and S-100. PMID- 26668524 TI - Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis. AB - OBJECTIVE: To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein induced acute pancreatitis. MATERIAL AND METHODS: In 30 Wistar albino rats (male; 240-260 g), acute pancreatitis was induced by an intraperitoneal injection of cerulein (50 MUg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained. RESULTS: Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose-dependent manner (35% in Group 2, 75% in Group 3; p=0.048). CONCLUSION: Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied the specific inhibition of inflammatory response pathways. PMID- 26668526 TI - How to approach phyllodes tumors of the breast? AB - OBJECTIVE: Phyllodes tumor of the breast is a rare fibroepithelial breast tumor that comprise 0.3-0.9% of primary breast neoplasms. In this study, we aimed to present clinicopathologic symptoms of our patients along with their treatment modality. MATERIAL AND METHODS: Clinicopathologic properties and treatment modality of 20 phyllodes tumor patients who underwent surgery between January 2008 and January 2013 were retrospectively evaluated. RESULTS: Median patient age was 47 years (22-75). Fine-needle aspiration biopsy was applied to 19 patients. Biopsy results were reported as suspicious in four, malignant in three, benign in 11, and as non-diagnostic in one patient. Final histopathology reports revealed two benign, one malignant and one borderline tumor out of the four patients with suspicious findings on fine needle aspiration biopsy; all patients with malignant cytology had malignancy. There were two borderline and nine benign lesions within the benign biopsy group. Sixteen patients underwent segmental mastectomy, four patients underwent mastectomy with/without axillary dissection. The median tumor size was 6 (1-13) cm. Histopathologically, 11 (55%) tumors were benign, 5 (25%) were borderline, and 4 (20%) were malignant. Two of the four patients with malignancy underwent radiotherapy and chemotherapy, and one patient only received chemotherapy as adjuvant treatment. CONCLUSION: Phyllodes tumors are rare, mix type breast tumors. Due to high rates of local recurrence and potential for malignancy, preoperative diagnosis and accurate management are important. PMID- 26668525 TI - Serum Galectin-3: diagnostic value for papillary thyroid carcinoma. AB - OBJECTIVE: Thyroid cancer constitutes approximately 1% of all cancers, approximately 90% of the endocrine malignancies, and is responsible for 0.4% of cancer-related deaths. Additional markers are required for the accurate diagnosis of thyroid malignancies. There is no marker that can accurately facilitate pre operative benign-malignant differentiation of thyroid nodules. The present study aims to evaluate the diagnostic value of preoperative serum Galectin-3 levels in thyroid cancer and to avoid unnecessary aggressive interventions. MATERIAL AND METHODS: Sixty-four patients who were operated between May 2009 and April 2011 were included in this study prospectively. Patients with toxic nodules and those with malignancies detected in preoperative fine needle aspiration biopsies (FNAB) were excluded. Patients with thyroid nodules of >3 cm in ultrasonography or having suspicious cytological findings in their preoperative FNABs regardless of the nodule size were included. Patients were divided into 2 groups, "control"and "cancer," according to the postoperative pathology results. RESULTS: The control group included 50 and cancer group included 14 patients. The mean age of the control group was 44.84+/-13.17 (19-79), while it was 44.14+/-15.94 (25-72) in the cancer group. A statistically significant difference was found between Galectin-3 levels in the cancer and control groups (p<0.001). CONCLUSION: In the present study, serum Galectin-3 levels in patients with malignant nodules were statistically significant. PMID- 26668527 TI - The effect of laparoscopic sleeve gastrectomy on morbid obesity and obesity related comorbidities: A cohort study. AB - OBJECTIVE: Bariatric surgery with multidisciplinary management is a more effective method to treat morbid obesity and obesity-related comorbidities compared with nonsurgical treatments. Laparoscopic sleeve gastrectomy (LSG) was initially performed as the first stage of biliopancreatic diversion with duodenal switch in the super-obese population. In the past few years, however, LSG has been performed as a definitive procedure because of its promising early and midterm results. The aim of this study is to evaluate the efficacy of our initial LSG series of 73 patients on excess weight loss (EWL) and resolution of obesity related comorbidities in short-term follow-up. MATERIAL AND METHODS: From March 2013 to May 2014, 78 morbid obese patients with an average body mass index (BMI) of 46.3 kg/m(2) underwent LSG. There is a 9-month follow-up period on average. Five patients were excluded from the study, because they could not be contacted. Comorbidities, preintervention BMI, glucose, HbA1c, and lipid profiles were recorded at 1, 6, and 12 months postintervention. RESULTS: After the surgery, the percent EWL was 58%. The mean serum glucose level, HbA1c level, LDL-cholesterol level, triglyceride level, insulin, and insulin resistance decreased significantly and the mean HDL-cholesterol level increased. CONCLUSION: For the resolution of comorbidities, LSG may be used as an effective bariatric and metabolic surgery. PMID- 26668528 TI - HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. AB - OBJECTIVE: Human epidermal growth factor-2 (HER-2) overexpression has prognostic value in breast cancer. However, the significance of HER-2 positivity in gastric cancer is controversial. In this study, we investigated the frequency of overexpression of HER-2 and its relationship with clinicopathological findings and impact on survival in gastric cancer. MATERIAL AND METHODS: Gastric cancer patients, operated in Marmara University Faculty of Medicine, Pendik Training and Research Hospital, General Surgery Department, between January 2012-December 2013 were enrolled in this study. Medical records were retrospectively evaluated. Tissue samples were stained by immunohistochemistry (IHC) method, and were followed by fluorescence in situ hybridization (FISH) in those with positive results. HER-2 expression rates and its association with other histopathological features and survival have been analyzed. RESULTS: 135 patients were enrolled in the study, with 88 (65%) male and 47 (35%) female patients. The median age was 61 (29-84) years. Only 11 patients (8%) were positive for HER-2. HER-2 positive patients were similar to negative patients in terms of age, gender, tumor size, tumor location, tumor T stage, lymph node metastasis, histological type, differentiation, lymphovascular invasion, perinodal, perineural invasion and stage. No significant difference was detected on 1 and 2-year overall and disease free survival rates between receptor positive and negative groups. CONCLUSION: Consistent with the literature data, HER-2 positivity rate in this study was approximately 8%, but this positivity has not been found to be associated with either clinical and pathological parameters or overall and disease-free survival. PMID- 26668529 TI - Thyroid cancer incidence in simultaneous thyroidectomy with parathyroid surgery. AB - OBJECTIVE: Primary hyperparathyroidism (PHPT) is often seen in conjunction with an underlying thyroid disorder. Imaging methods that are used to localize the parathyroid adenoma also detect associated thyroid nodules and thyroid cancer. The aim of this study was to detect the rate of thyroid cancer identified while performing parathyroidectomy and thyroidectomy in patients with PHPT. MATERIAL AND METHODS: Files of all patients who were operated for PHPT and who underwent simultaneous thyroidectomy were analyzed. Data regarding parathyroid pathology, surgical procedures, indications of thyroid surgery, and pathology results were retrospectively recorded. The indications for thyroid surgery included presence of suspicious thyroid nodules in ultrasonography, increase in size of thyroid nodules in follow-up ultrasound, or presence of suspicious thyroid fine needle aspiration biopsy (FNAB) findings. Rates of thyroid cancer detection were investigated according to definite pathology reports. RESULTS: Eighty-three patients who underwent parathyroidectomy with a diagnosis of PHPT with concurrent thyroidectomy in Department of General Surgery, Istanbul University Istanbul Faculty of Medicine were included in the study. Eighteen patients were male (22%) and 65 were female (78%). The median age was 53 (18-70) years. The primary indication for parathyroidectomy was primary hyperparathyroidism in all patients. The thyroid procedures applied in addition to parathyroidectomy were lobectomy + isthmusectomy in 29 patients (35%), bilateral subtotal thyroidectomy in 20 patients (24%), bilateral total thyroidectomy in 23 patients (28%), and total thyroidectomy on one side and near total thyroidectomy to the other side in 11 patients (13%). The only indication for thyroidectomy was the presence of thyroid nodules until 2000 (20 patients, 24%). Indications in the remaining 63 patients included the presence of multiple nodules that cannot be followed up by ultrasonography in 25 patients (30%), presence of a suspicious nodule on ultrasonography in 33 patients (40%), growth in nodule size in 2 patients (2%), and detection of suspicious findings on FNAB in 3 patients (4%). Five patients (6%) were diagnosed with papillary thyroid cancer, four of whom were micropapillary cancer. CONCLUSION: Imaging methods performed to localize the pathological parathyroid gland for a diagnosis of PHPT are useful in estimating other accompanying pathologies. Presence of thyroid nodules should be evaluated before all parathyroid procedures, and if the nodule has an indication for surgery, thyroid surgery should be considered at the same operation with parathyroid surgery. PMID- 26668530 TI - Adjuvant versus neoadjuvant chemoradiotherapy in distal rectal cancer: Comparison of two decades in a single center. AB - OBJECTIVE: Standard surgery alone was not able to decrease local recurrence (LR) rate below 20% in rectal cancer treatment. Thus, many centers administered neoadjuvant radiotherapy (preopRTx) with or without concomitant chemotherapy for the prevention of LR. In this study, the results of 164 consecutive patients with mid- and distal rectal cancer who received surgery and adjuvant chemoradiotherapy (Group A) or neoadjuvant chemoradiotherapy (Group NA) followed by surgery are presented. MATERIAL AND METHODS: The staging system used in this study is that of the American Joint Committee on Cancer (AJCC), also known as the TNM system. Eligible patients were required to have radiologically assessed stage 1 (only T2N0M0) to stage 3C (T4bN1-2M0) tumor with pathologically confirmed R0 resection. The surgical method was total mesorectal excision (TME). Radiotherapy was applied with daily 180 cGy fractions for 28 consecutive days. Chemo-therapy comprised 5 fluorouracil (450 mg/m(2)/d) and leucovorin (20 mg/m(2)/d) bolus at days 1-5 and 29-33. RESULTS: Nine patients (13%) in Group NA achieved pathologic complete response (pCR). In Group NA and Group A, locoregional recurrence (LRR) rates were 6.7% and 30.8%, (p<0.001), the mean LR-free survival was 190.0+/-7.3 months and 148.0+/-11.7 months (p=0.002) and the mean overall survival (OS) was 119.2+/-15.3 months and 103.0+/-9.4 months (p=0.23), respectively. A significant difference with regard to LR has been obtained with a statistical power of 0.92. Secondary outcome measures (DFS and OS) have not been met. CONCLUSION: Neoadjuvant chemoradiotherapy with TME is an efficient treatment protocol, particularly for the treatment of magnetic resonance imaging-staged 2A to 3C patients with two or three distal rectal adenocarcinomas. Given that a considerable proportion of patients with cT2N0M0 would develop pCR, this method of treatment can be considered for further studies. PMID- 26668531 TI - Should appendectomy be performed laparoscopically? Clinical prospective randomized trial. AB - OBJECTIVE: Laparoscopic appendectomy (LA) has been described in 1983, and its superiority over open appendectomy (OA) is still being debated. Currently, there is no agreement on the advantages of LA. Postoperative pain is reported to be lower along with a faster return to normal activities in LA. However, some studies do not support these findings. In our study, we aimed to compare the outcomes and cost effectiveness of LA and OA. MATERIAL AND METHODS: Patients were prospectively randomized into LA (31 patients) and OA (32 patients) groups. Demographic data, pre- and postoperative C-reactive protein (CRP) levels, white blood cell (WBC) count, duration of surgery and hospitalization, complications, and pain scores (VAS) were recorded. Cost was calculated for both groups. Return to normal activities was evaluated by phone calls at the first and second week and 1 month after surgery. RESULTS: There was a significant postoperative decrease in WBC count in the LA group (p<0.01). There were no differences between LA and OA groups in terms of postoperative CRP levels (p>0.05). The rates of wound infection and abscess were similar (p>0.05), while post-operative pain and time to return to normal activities were higher in the OA group (p<0.01). There was a positive correlation between BMI and operative time in the LA group (p<0.01), while BMI and operative time did not show a correlation in the OA group (p>0,05). The average cost in the LA and OA groups were 1960.5+/-339.05 and 687.115+/-159.5 TL, respectively. CONCLUSION: LA is an effective method in the treatment of acute appendicitis due to less pain and faster recovery. LA can be the choice of treatment in acute appendicitis, with utilization of re-useable and cheaper vascular sealing devices. PMID- 26668532 TI - Methods for closure of appendix stump during laparoscopic appendectomy procedure. AB - The most frequent abdominal pathology requiring emergent surgery is acute appendicitis. Laparoscopic appendectomy has been performed for the treatment of acute appendicitis since 1983. Closure of the appendix stump is vital to prevent severe postoperative complications. Different methods are described for closure such as stapler, endoloop, titanium clips, non-absorbable polymer clips (hem-o lok clip), handmade loops, transsection by Ligasure or with bipolar cautery. The ideal method should be safe, applicable and cheap. The most appropriate method remains to be controversial. All methods are reported as safe, but some have higher costs, and some prolong the operation. In this article, we reviewed clinical and experimental studies on different methods of stump closure, and we tried to compare the benefit of these methods over others. PMID- 26668533 TI - Living donor liver transplantation in an adult patient with situs inversus totalis. AB - Situs inversus totalis (SIT) is a rare congenital anomaly, and liver transplantation (LT) in an adult SIT patient is extremely rare. Liver transplantation in a SIT patient is also technically challenging due to reversed anatomical structures. Here we present the case of an 18-year-old female with SIT in whom left lobe living donor LT was performed. The patient suffered from cirrhosis due to autoimmune hepatitis. The recipient and donor are doing well without complications 20 months after LT. Situs inversus totalis should not be considered a contraindication for LT. If possible, use of a living donor left lobe graft for LT is more feasible than a living donor right lobe graft. It is also technically easier than using deceased donor full-size liver graft in SIT patients who require liver transplantation. PMID- 26668534 TI - Co-existent breast and renal cancer. AB - The concomitant presence of breast cancer with one or more other types of cancer such as colon, vulva, lung, larynx, liver, uterus and kidneys has been presented in the literature. However, synchronous breast and renal cancer is very uncommon. Herein we present a woman with synchronous breast and renal cancer, and review the literature. A 77-year-old post-menopausal woman was admitted to our clinic complaining of left sided breast mass. On physical examination, there was a 3 cm palpable mass in the upper outer quadrant of the left breast along with a conglomerate of lymph nodes in the left axilla. Ultrasonography and mammography showed a 3 cm solid, hypoechoic mass in the upper outer quadrant and left axillary lymphadenopathy. The tru-cut biopsy of the lesion revealed invasive ductal carcinoma. The bone scintigraphy, thoracic and cranial computerized tomographies were normal. The abdominal computerized tomography identified a 3*3 cm solid renal mass with heterogeneous contrast enhancement in the posterior segment of the lower pole, which was suspicious for renal cell carcinoma. Breast conserving surgery and axillary lymph node dissection was performed, and the pathology specimen demonstrated invasive ductal carcinoma. The patient was discharged on postoperative day 5. Three weeks later partial nephrectomy was performed by urology department for the solid renal mass, and the pathology result showed clear cell-renal carcinoma with Fuhrman grade 3. The patient is being followed-up for renal carcinoma, and underwent radiotherapy for breast cancer. Hormonotherapy for breast cancer is still continuing. PMID- 26668535 TI - Idiopathic encapsulating sclerosing peritonitis. AB - Sclerosing encapsulating peritonitis (SEP)/abdominal cocoon syndrome is a rare condition that is generally identified in young females. The exact cause is still unknown. Timely and accurate imaging and diagnosis play a critical role for morbidity and mortality. It is usually diagnosed during surgery. The initial treatment should be conservative, and aggressive surgical approach should be avoided as much as possible. Herein, we aimed to review the clinical features of SEP based on a patient who underwent surgery in our clinic. PMID- 26668536 TI - Intrahepatic splenosis after splenectomy performed for idiopathic thrombocytopenic purpura. AB - The term splenosis describes autotransplantation or implantation of ectopic splenic tissue within the abdominal cavity or in any other unusual body compartment. In addition to the diagnostic dilemma it causes, splenosis may also lead to persistence or recurrence of hematologic dysfunctions by its preserved immune activity especially in cases of splenectomy due to hematologic indications. Herein, we present a 40-year-old female who had splenectomy for idiopatic thrombocytopenic purpura, and was identified to have splenic tissue within left lobe of the liver during further assessment of ongoing thrombocytopenia. PMID- 26668537 TI - Endometriosis within the sigmoid colon/extragenital endometriosis. AB - Endometriosis is the presence of endometrial glands and stroma outside the uterine cavity. Although it is common in women in the reproductive age, intestinal endometriosis is extremely rare and may lead to serious clinical problems. In this article, we present two rare cases of endometriosis localized in the sigmoid colon lumen. The first case is a 45 year-old female complaining of rectal bleeding for 6 months. A polypoid lesion with suspicion of malignancy, 3-4 cm in size was identified at colonoscopy. Laparoscopic anterior resection was performed since it was not suitable for colonoscopic polypectomy. The pathology examination revealed extragenital endometriosis. The second case is a 36 year-old female admitted for lower abdominal pain and rectal bleeding for the last 3 months. She was diagnosed with sigmoid diverticulitis. The patient's symptoms regressed with medical treatment, but due to early and multiple recurrent episodes it was decided to perform an elective laparoscopic anterior resection. The pathology report stated diverticulosis coli and intraluminal endometriosis. Intestinal endometriosis should be considered as part of the differential diagnosis in female patients of the reproductive age who present with constipation, gastrointestinal bleeding, nausea, vomiting, cramp-like abdominal pain, diarrhea and pelvic pain. In these patients, resection and anastomosis of the effected bowel segment is accepted as the choice of treatment. PMID- 26668538 TI - Is sentinel lymph node biopsy enough for axillary macrometastasis? PMID- 26668539 TI - New species of Cerambycidae (Coleoptera) from South and Central America. AB - Three new species are described: Tropidion birai (Cerambycinae, Neoibidionini) from Bolivia; Chrysoprasis birai (Cerambycinae, Heteropsini) from Panama; and Recchia nearnsi (Lamiinae, Aerenicini) from Bolivia. The new species are included in amended versions of previously published keys to species of each genus. PMID- 26668540 TI - Checklist of tapeworms (Platyhelminthes, Cestoda) of vertebrates in Finland. AB - A checklist of tapeworms (Cestoda) of vertebrates (fishes, birds and mammals) in Finland is presented, based on published observations, specimens deposited in the collections of the Finnish Museum of Natural History (Helsinki) and the Zoological Museum of the University of Turku, and additional specimens identified by the present author. The checklist includes 170 tapeworm species from 151 host species, comprising 447 parasite species/host species combinations. Thirty of the tapeworm species and 96 of the parasite/host species combinations have not been previously reported from Finland. The total number of tapeworm species in Finland (170 spp.) is significantly lower than the corresponding figure for the Iberian Peninsula (257 spp.), Slovakia (225 spp.) and Poland (279 spp.). The difference between Finland and the other three regions is particularly pronounced for anseriform, podicipediform, charadriiform and passeriform birds, reflecting inadequate and/or biased sampling of these birds in Finland. It is predicted that there are actually ca. 270 species of tapeworms in Finland, assuming that true number of bird tapeworms in Finland corresponds to that in other European countries with more comprehensive knowledge of the local tapeworm fauna. The other main pattern emerging from the present data is the seemingly unexplained absence in (northern) Fennoscandia of several mammalian tapeworms that otherwise have extensive distributions in the Holarctic region or in Eurasia, including the northern regions. Previously unknown type specimens, that is, the holotype of Bothrimonus nylandicus Schneider, 1902 (a junior synonym of Diplocotyle olrikii Krabbe, 1874) (MZH 127096) and the syntypes of Caryophyllaeides fennica (Schneider, 1902) (MZH 127097) were located in the collections of the Finnish Museum of Natural History. PMID- 26668541 TI - A catalogue of the scaleworm genus Lepidonotus (Polynoidae, Polychaeta) from South America, with two new records for Brazilian waters. AB - The genus Lepidonotus is the largest in number of species within the Polynoidae, with more than 70 described species and subspecies. A catalogue of 18 nominal species and subspecies of Lepidonotus from South America is provided, with valid names, synonyms and original citations. Redescriptions and illustrations of two species based on new specimens collected along the littoral of the State of Paraiba, northeastern Brazil are included. Lepidonotus carinulatus and Lepidonotus natalensis are reported for the first time for Brazilian waters. A comparative table of characters for all reported species and subspecies of Lepidonotus from South America is provided. PMID- 26668542 TI - Phytoseiid mites from tropical fruit trees in Bahia State, Brazil (Acari, Phytoseiidae). AB - The cultivation of tropical fruit trees has grown considerably in the state of Bahia, northeastern Brazil. Some of these have been severely attacked by phytophagous mites, which are usually controlled by the use of chemical pesticides. However, there is today a growing interest for the adoption of less aggressive measures of pest control, as for example the use of predatory mites. Most of the plant-inhabiting predatory mites belong to the family Phytoseiidae. The objective of this paper is to report the phytoseiid species found in an intensive survey conducted on cultivated tropical fruit trees in fifteen localities of the southern coast of Bahia. Measurements of relevant morphological characters are provided for each species, to complement the understanding of the morphological variation of these species. Twenty-nine species of sixteen genera were identified. A key was elaborated to assist in the separation of these species. Fifteen species are reported for the first time in the state, raising to sixty-six the number of species of this family now known from Bahia. Seventy-two percent of the species collected belong to Amblyseiinae, followed by Typhlodrominae (21%) and Phytoseiinae (7%). The most diverse genus was Amblyseius. Amblyseius operculatus De Leon was the most frequent and abundant species. Studies should be conducted to evaluate the possible role of the most common predators as control agents of the phytophagous mites co-occurring with them. PMID- 26668543 TI - A new Antaeotricha species from Florida sandhills and scrub (Lepidoptera, Depressariidae, Stenomatinae). AB - Antaeotricha floridella sp. n. is described and diagnosed from the closely similar Antaeotricha albulella (Walker). The species is distributed in xeric sandhill and scrub habitats in peninsular Florida, USA, and larvae feed on Quercus species. Keys are given for pale-winged Stenomatinae and similar Gelechioidea based on external characters and genitalia. PMID- 26668544 TI - Eriophyoid mites (Acari, Eriophyoidea) associated with tea plants, with descriptions of a new genus and two new species. AB - A new genus and two new species of mites in the family Eriophyidae, Theaphyes rapaneae gen. n. and sp. n. which is found on the type host Rapanea neriifolia (Sieb. et Zucc.) Mez (Myrsinaceae) and Paracaphyllisa theacea sp. n., are described and illustrated. They are vagrants on the tea plant Camellia sinensis (L.) Kuntze and no apparent symptoms were detected. A key to the eriophyoid mites including thirteen species associated with tea plants all over the world is provided. PMID- 26668545 TI - A new genus and species of cyclopoid (Crustacea, Copepoda, Cyclopinidae) from a coastal system in the Gulf of Mexico. AB - A new, monotypic genus of the interstitial marine cyclopoid copepod family Cyclopinidae G.O. Sars, 1913 is described from male and female specimens collected at Laguna de Terminos, a large coastal lagoon system in the southern Gulf of Mexico. Mexiclopina campechana gen. et sp. n. cannot be adequately placed in any extant genus within the family. It differs from other cyclopinid genera in having a unique combination of characters including: 1) absence of modified brush like seta on the mandibular exopod; 2) maxillule exopod with stout setal elements and brush-like setae absent; 3) basis of mandible with one seta; 4) presence of a modified seta on endopod of fourth leg; 5) fifth leg exopod unsegmented, armed with three elements in the female and five in the male; 6) intercoxal sclerite of first swimming leg with two medial spiniform processes on distal margin. The new genus is monotypic and appears to be most closely related to Cyclopina Claus, 1863 and Heptnerina Ivanenko & Defaye, 2004; the new species was compared with species of Cyclopina and it resembles Cyclopina americana Herbst, 1982 and Cyclopina caissara Lotufo, 1994. This is the second record of a species of Cyclopinidae in Mexico and the first in the Gulf of Mexico; the number of cyclopinid species recorded from the Americas is now 13. PMID- 26668546 TI - Catalog of the adelgids of the world (Hemiptera, Adelgidae). AB - A taxonomic and nomenclatural Catalogue of the adelgids (Hemiptera: Adelgidae) is presented. Six family-group names are listed, five being synonyms of Adelgidae. Twenty-two genus-group names, of which nine are subjectively valid and in use, are presented with their type species, etymology, and grammatical gender. One hundred and six species-group names are listed, of which 70 are considered subjectively valid. PMID- 26668547 TI - Paratullbergia Womersley in China: the description of a new species and a key to the genus (Collembola, Tullbergiidae). AB - The genus Paratullbergia Womersley, 1930 is recorded for the first time from China. Paratullbergia changfengensis sp. n. from Shanghai is described and illustrated. It is characterized by the presence of 1+1 pseudocelli on thoracic segment I, with two pairs of pseudocelli on each of thoracic segments II and III, presence of seta px on abdominal segment IV, seta a2 and p4 on abdominal segment V as microsetae, and less differentiated sensory seta p3 on abdominal segment V. Both sexes present. The new species can be easily distinguished from its congeners by the presence of pseudocelli on thoracic segment I. An updated key to the world species of the genus Paratullbergia is provided. PMID- 26668548 TI - The genus Gymnetron from China with description of pre-imaginal stages of G. miyoshii, G. auliense and G. vittipenne (Coleoptera,Curculionidae). AB - There are four species of Gymnetron in China recorded to date including Gymnetron miyoshii Miyoshi, 1922, Gymnetron villosipenne Roelofs, 1875, Gymnetron auliense Reitter, 1907 and Gymnetron vittipenne Marseul, 1876, of which the last two are new country records. The pre-imaginal stages including eggs, mature larvae and pupae of Gymnetron miyoshii, Gymnetron auliense and Gymnetron vittipenne are described and illustrated. In addition, their diagnostic characters (larvae and pupae) are discussed and differentiated, and notes on some of their biological parameters are provided. Potential ecological impacts between Gymnetron weevils and their host Veronica spp. also are provided. PMID- 26668549 TI - Review of the genus Hieromantis Meyrick from China, with descriptions of three new species (Lepidoptera, Stathmopodidae). AB - Six species of the genus Hieromantis occurring in China are reviewed. Hieromantis rectangula sp. n., Hieromantis arcuata sp. n. and Hieromantis puerensis sp. n. are described as new, and Hieromantis phaeodora Meyrick, 1929 is newly recorded in China. Photographs of adults and illustrations of genitalia are provided, along with an identification key and a distribution map. PMID- 26668550 TI - Description of a new genus and three new species of Otothyrinae (Siluriformes, Loricariidae). AB - The genus Hisonotus was resurrected as a member of the tribe Otothyrini (actually subfamily Otothyrinae). However, phylogenetic studies based on morphological and molecular data showed that Hisonotus is not monophyletic and independent lineages can be identified, such as the group composed of the species Hisonotus insperatus, Hisonotus luteofrenatus, Hisonotus oliveirai, Hisonotus paresi and Hisonotus piracanjuba, a lineage unrelated to that containing the type species of the genus Hisonotus (Hisonotus notatus). Herein, based in molecular and morphological data, a new genus is described to accommodate the lineage mentioned above, into which are also added three new species. This new genus can be distinguished from other genera of Otothyrinae by the following combination of characters: (1) a pair of rostral plates at the tip of the snout; (2) two large pre-nasal plates just posterior to the rostral plates; (3) a supra-opercular plate that receives the laterosensory canal from the compound pterotic before the preopercle; (4) a well developed membrane at anal opening in females; and (5) a V shaped spinelet. A key to species of Curculionichthys is provided. PMID- 26668551 TI - Genetic divergence analysis of the Common Barn Owl Tyto alba (Scopoli, 1769) and the Short-eared Owl Asio flammeus (Pontoppidan, 1763) from southern Chile using COI sequence. AB - In this paper new mitochondrial COI sequences of Common Barn Owl Tyto alba (Scopoli, 1769) and Short-eared Owl Asio flammeus (Pontoppidan, 1763) from southern Chile are reported and compared with sequences from other parts of the World. The intraspecific genetic divergence (mean p-distance) was 4.6 to 5.5% for the Common Barn Owl in comparison with specimens from northern Europe and Australasia and 3.1% for the Short-eared Owl with respect to samples from north America, northern Europe and northern Asia. Phylogenetic analyses revealed three distinctive groups for the Common Barn Owl: (i) South America (Chile and Argentina) plus Central and North America, (ii) northern Europe and (iii) Australasia, and two distinctive groups for the Short-eared Owl: (i) South America (Chile and Argentina) and (ii) north America plus northern Europe and northern Asia. The level of genetic divergence observed in both species exceeds the upper limit of intraspecific comparisons reported previously for Strigiformes. Therefore, this suggests that further research is needed to assess the taxonomic status, particularly for the Chilean populations that, to date, have been identified as belonging to these species through traditional taxonomy. PMID- 26668552 TI - Annotated check list of the Pyraloidea (Lepidoptera) of America North of Mexico. AB - An annotated check list of Pyraloidea of North America north of Mexico is presented, including 861 Crambidae and 681 Pyralidae with 1542 total species. It includes all new species described, tropical species with new records in the United States, and species introduced from Europe and Asia since 1983. The Notes section provides the seminal citations, data and/or commentary to all changes since 1983 for easy and future reference. In addition, this list proposes seven new generic combinations, the transfer of a phycitine species, Salebria nigricans (Hulst), to Epipaschiinae and its syn. n. with Pococera fuscolotella (Ragonot), and three new records for the United States. Purposefully, no new taxa are described here, but we found a gradual increase of 10% in the number of species described since 1983. Finally, we also include a list of thirteen species not included or removed from the MONA list. Many higher-level changes have occurred since 1983 and the classification is updated to reflect research over the last 30 years, including exclusion of Thyrididae and Hyblaeidae from the superfamily and recognition of Crambidae and Pyralidae as separate families. The list includes multiple changes to subfamilies based on morphology such as the synonymization of the Dichogamini with the Glaphyriinae, but also incorporating recent molecular phylogenetic results such as the synonymization of the Evergestinae with the Glaphyriinae. PMID- 26668554 TI - EBA - MBC. PMID- 26668553 TI - Editorial. PMID- 26668555 TI - Abdominal compartment syndrome (ACS) in a severely burned patient. AB - Abdominal compartment syndrome (ACS) occurs when increasing intra abdominal pressure (IAP) reduces blood flow to abdominal organs. This results in impairment of pulmonary, cardiovascular, renal, hepatic, central nervous system and gastro intestinal (gi) function, causing multiple organ dysfunction syndrome and death. The significant prognostic value of elevated intra-abdominal pressure has prompted many intensive care units to adopt measurement of this physiologic parameter as a routine vital sign in patients at risk. ACS generally occurs in patients who are critically ill due to any of a wide variety of medical and surgical conditions. it has been recently described as a rare complication of burn injury. it is fundamental to: 1) recognize IAP and ACS; 2) resuscitate effectively; and 3) prevent the development IAP-induced end-organ dysfunction and failure. We present our recent experience with one patient suffering from ACS secondary to burn injury and the physiologic results of abdominal wall escharotomy. PMID- 26668556 TI - The clinical efficacy of Diphoterine(r) in the management of cutaneous chemical burns: a 2-year evaluation study. AB - Diphoterine((r)) is an amphoteric irrigating agent for the treatment of chemical burns and rapidly neutralises both acids and alkalis faster than water alone. Diphoterine((r)) is widely used as a first aid agent in a wide range of industries globally. This is a retrospective review of the clinical use of Diphoterine((r)) on chemical burns in an adult tertiary referral burn centre, often with a delay of several hours after the injury. patients admitted with chemical burns within 24 hours of the incident with an abnormal wound pH or in pain, were treated with Diphoterine((r)) spray. Over a 32-month period, 1,875 burn referrals were admitted of which 131 (7%) were chemical burns. Diphoterine((r)) was used in 47 patients (36%). The male to female ratio for the 131 patients was 4:1. Alkaline burns were the commonest (55%). patients who received Diphoterine((r)) were significantly younger (38 vs 43 years; p=0.05) and presented earlier (0.5 vs 2.55 days; p=0.004). There was a significant change in the wound pH pre- and post-application of Diphoterine((r)), compared to patients who were treated with water irrigation only, with a pH change of 1.076 vs 0.4 (p <0.05). There was no significant difference in the time to healing, the length of hospital stay, or need for surgery. in conclusion, based on our retrospective cohort, Diphoterine((r)) could be a valuable tool for use in hospital settings to neutralise both alkaline and acid burns. PMID- 26668557 TI - [Not Available]. AB - The use of bacteriophages, natural predators of bacteria, is an effective technique in the fight against bacterial infections. Long since forgotten in the western world, it is still practised in parts of Eastern Europe as the primary weapon of choice against bacterial infections in public health policy. The global emergence of multidrug-resistant bacteria, or " superbugs ", and the associated risk of returning to the pre-antibiotic era have brought the benefits of phagotherapy back to the fore. The purpose of this paper is to highlight the biology and place of bacteriophages in their natural context and explain why and how phagotherapy can be an effective solution to treat bacterial infections. PMID- 26668559 TI - Optimal timing for burned hands in children. AB - Hand burns in children are frequent, severe, and require adequate treatment. A fundamental, though problematic aspect of this treatment is the assessment of the burn depth as this determines the surgical strategy. From a retrospective study of 369 hand burns admitted to our clinic, we were able to identify some patterns. A total of 14.91% required surgery, with varying etiology among these patients. Differences were also noticed in the number of days post-burn prior to surgical intervention. The patterns revealed by our results are reviewed in order to improve therapeutic strategy. PMID- 26668560 TI - [Not Available]. AB - Burn injuries to the hand are still common in low-income countries. Between December 1st 2010 and May 1st 2014, 32 patients, representing 38 hands, were admitted and treated at the University Clinics of Kinshasa in the Democratic Republic of Congo (DRC). We observed 22 patients (69%) in the juvenile age group (under 18 years old) and 10 patients (31%) in the adult age group (18-59 years). We did not observe any patients in the senior age group (60 years and over). In the juvenile age group, those aged from 1 to 5 years old were the most affected, comprising 13 patients (40%). Accidents occurred mainly at home (72%). The most common burn etiologies were thermal injuries caused by flame (51%) and scalds (34%). Contractures were the most frequently occurring lesions (84%). Overall dorsal retraction, known as "claw hand", was found in 40% of patients, and was associated with keloid and hypertrophic scars in 84% of cases. Excision and grafting were performed in 43.7%, local flaps in 43.7% and distant flaps in 12.5% of cases. On discharge from hospital, 84% "good" results were observed. Follow-up lasted 18 months. This study demonstrates the feasibility of reconstructive surgery in sequelae of hand burns, despite limited resources. However, the challenges in low income countries with limited resources are numerous: poor access to current techniques of plastic surgery, inadequate initial burns management, and poverty. PMID- 26668561 TI - Microsurgery in the burn population - a review of the literature. AB - The management of patients suffering from burn injury poses unique challenges for the reconstructive surgeon, both in the acute and delayed settings. Once resuscitative measures are optimized and hemodynamic stability is achieved, early burn debridement and coverage is performed. Traditionally, this consists of excision of devitalized tissue and subsequent coverage using split thickness skin grafts. However, in certain instances, and depending on the extent and nature of the burn injury, skin grafting (or even local tissue rearrangement) may not be a reasonable option. in these cases, free tissue transfer may provide a viable reconstructive alternative. While free flap reconstruction is rare in burn surgery, particularly in the acute setting, burn injuries that expose vital structures, such as tendon, nerve, bone, or deep vessels, require robust flap coverage. in the delayed setting, unsightly scar formation and contracture often occurs secondary to skin graft coverage. These significant patient morbidities are often amenable to free tissue transfer as well. This review article discusses the indications, applications, and problems with free flap surgery for burn injuries in both the acute and delayed setting, and summarizes the available literature on microsurgical free tissue transfer for burn management. PMID- 26668558 TI - [Not Available]. AB - Local or general fungal infection remain a very serious event in burns. Burns have numerous risk factors for such, infections associated with depressed immunity. Candida, Aspergillus and mucor fungi prevail in wound infections. The two latest are especially serious and impairing. Diagnosis is based on anatomo pathological and mycological examination of skin samples. Treatment is mainly surgical. Medical therapy depends on antifungal susceptibility. Most fungemias are candidemias. Diagnosis is difficult and often based on clinical suspicion. Treatment uses echinocandin and fluconazole. PMID- 26668562 TI - Management of complex pediatric burn scars in a humanitarian collaboration. AB - Burn scars still represent a challenge to the reconstructive surgeon. Their management requires a specific expertise and set up involving the possibility of long term rehabilitation and follow up. Cases encountered in humanitarian missions present additional issues. Often the local environment is not suitable for an appropriate treatment plan, requiring the case to be transferred to a foreign country for surgical care as part of an integrated international and multidisciplinary management. We present the case of a three year-old patient injured in a bomb explosion during the Arab Spring and suffering from severe scar contracture limiting thoracic and upper limb movement. After initial consultation at distance, transfer to our country was organized and an intensive surgical and rehabilitative program was carried out over three months. After five months, the patient returned to his home country where a supportive network had been set up for continued rehabilitation, ensuring follow up for over a year and ultimate success. PMID- 26668563 TI - [Not Available]. AB - Disaster situations involving mass burn casualties can occur at any time after a fire, a terrorist attack, an industrial explosion or a transport accident. The various burn societies in the world published recommendations on disaster burn care planning. French burn society (Societe Francaise d'Etude et de Traitement des Brulures-SFETB) proposes triage of burned victims according to Total Burn Surface Area (TBSA), inhalation injury and associated traumatic injuries. This plan seeks to classify victims and to refer each burned patient to a bed suited to its needs (burn centre, surgical or medical ICU, Emergency room, surgical ward and triage). Emergency Medical Services play a pivotal role in this organisation: first care, advanced medical post, medical coordination, triage and transportation, additional equipment supply in proximal hospital. Burn disaster plan should be adapted to local medical resources. PMID- 26668564 TI - [Not Available]. AB - The best treatment for victims of severe burns is provided in highly specialised burn centres. Due to the paucity of these centres, long distance aeromedical evacuation is often required. However, published data regarding such transfers are scarce. In this review, in order to help optimize patient management when air transportation is decided or even only considered, we propose simple principles derived from this limited literature and backed by the practical experience of the French military. We first describe how specific flight conditions may impact transportation of severe burn patients aboard aircraft. We then focus on the planning and organisation of these transfers discussing the risks associated with air transportation of such patients and their implications on indication, timing and modality of transport. Finally, provide an end-to-end view of the process from pre-flight equipment preparation, pre-boarding patient assessment and conditioning, to in-flight care. PMID- 26668565 TI - Saturday night burns: an increasing problem? AB - In Italy the economic crisis has caused changes in behavior in daily as well as leisure activities. For instance, night clubs have changed both their scenography and what they can offer. From simply providing a place to dance, they can now offer more complex scenography with spectacular fireworks and lit cocktails. While this can be amazing for all of us it can also be another cause of burn injuries. We conducted a retrospective study of all burns patients admitted to the Accident and Emergency Department at CTO Hospital in Turin from 2009 to 2013, after a night clubbing. A total of five patients were identified with an average age of 20 years old: four were burned by flaming cocktails and one was burned by a firework. Two received outpatient treatment, while orotracheal intubation and admission were needed for three, and two required surgical debridement and resurfacing with split skin graft. All patients had permanent sequelae caused by pathologic scarring and/or dyschromia. Our findings show that the risk of burn injuries is higher at weekends, mainly in summer, if all correct safety procedures are not followed. Meanwhile it is important to highlight that the promotion of inappropriate behavior at night clubs during firework displays and the passing of flaming cocktails should be avoided. PMID- 26668567 TI - MBC News. PMID- 26668566 TI - Major burn injuries associated with Christmas celebrations: a 41-year experience from Switzerland. AB - In Switzerland it is customary to light candles on Christmas trees and advent wreaths. This tradition leads to an increased risk of home fires. We reviewed the records of patients who sustained burn injuries from a lit Christmas tree or advent wreath during the Christmas holidays between January 1971 and January 2012. We treated 28 patients and observed 4 fatalities (mortality rate: 14%). 61% of the patients were male, 39% were female. The mean abbreviated burn severity index (ABSI) was 6.5 points in the group of the survivors and 10.8 points in the group of the non-survivors. The mean total body surface area burned (TBSA) for survivors was 18.9%, with 14.1% having full thickness burns; for the non survivors the mean TBSA was 45.2%, with 38% having full thickness burns. The Mann Whitney U-test showed a significant difference between the survivors and the fatalities concerning the mean total and full thickness burned body surface area (p value 0.009 and 0.012). More than sixty percent of the fires occurred in January and the most severe accidents were seen after January 4th. Despite Christmas decoration-associated fires being relatively uncommon, they tend to cause more serious injuries than regular household fires. We recommend that in countries where it is customary to set up flammable Christmas decorations, state issued information pamphlets with instructions on fire safety conduct should be distributed. PMID- 26668568 TI - Exacerbation of Dermatomyositis with Recurrence of Rectal Cancer: A Case Report. AB - Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by cutaneous and muscle manifestations. The association between DM and malignancy has been well recognized for many years. The clinical course of paraneoplastic DM may be affected by malignancies, although the cause and effect relationship between exacerbation of DM and cancer progression is uncertain. Herein, we report a 44-year-old woman who presented with progressive DM associated with rectal cancer. After curative resection of rectal cancer, DM symptoms resolved. Three months after surgery, blood test surveillance showed elevation of serum carcinoembryonic antigen levels, although the patient remained asymptomatic. One month later she had a DM flare-up, and multiple lung and liver metastases were found. She immediately underwent cancer chemotherapy with prednisolone therapy for DM. However, her condition deteriorated and she was unable to swallow. Percutaneous endoscopic gastrostomy was constructed, allowing alimentation and oral delivery, which made it possible to keep her on chemotherapy. She had remarkable response for unresectable metastases 8 weeks after the administration of chemotherapy. Seven months after onset of recurrence, her condition improved considerably and she had stable disease. Moreover, she can now eat food of soft consistency. Our case provides further support for the clinical importance of cancer chemotherapy for patients who have progressive DM and unresectable rectal cancer. PMID- 26668569 TI - Sustained Improvement in a Metastatic Colon Cancer Patient with FOLFIRI Aflibercept after FOLFOX Failure. AB - The present report illustrates a case of a 37-year-old Indian male patient diagnosed with adenocarcinoma of the sigmoid colon who underwent an anterior resection with total mesorectal excision surgery. He was administered adjuvant chemotherapy with 10 cycles of a FOLFOX-4 (folinic acid, fluorouracil and oxaliplatin) regimen but developed relapse. He was then put on a FOLFIRI (folinic acid, fluorouracil and irinotecan)-aflibercept (Zaltrap) regimen and received 12 cycles during the next 6 months. During the treatment period, a reduction in ascites along with a decline in serum carcinoembryonic antigen (CEA) level was observed, though the tumor size was unchanged. After completion of 12 cycles, the patient was asymptomatic but showed signs of progression in the form of increased CEA level. The FOLFIRI-aflibercept therapy was discontinued, and the patient was given supportive treatment, but he eventually died after another 6 months. The FOLFIRI-aflibercept treatment provided a progression-free survival of 6 months and an overall survival of 1 year to this patient, which corroborates the findings of the VELOUR trial. PMID- 26668570 TI - Alternative Therapeutic Approach in the Treatment of Oral Pyogenic Granuloma. AB - Pyogenic granulomas (PGs) in the oral cavity present as an inflammatory hyperplasia usually caused by trauma, hormonal imbalance, chronic irritation, or as the response to a wide variety of drugs. PGs with atypical presentation and behavior may clinically mimic malignant tumors. Thus, histological examination is required to rule out cancer development. Lesions in the oral cavity have been described to be either an isolated entity or present in multiple forms and with multiple recurrences. Conservative surgical excision is the standard choice of treatment in almost every scenario. However, the severity of the lesions and the affected sites often challenge surgical treatment. In this report, we describe the clinical scenario of a recurrent PG, where surgical excision of the lesion was questioned. As an alternative, we describe a noninvasive approach with lesional steroid injections. PMID- 26668571 TI - Is It Contralateral Axillary Metastasis or Occult Breast Cancer?: A Confusing Case Report. AB - We report the case of a 43-year-old woman with primary left breast cancer presenting metastatic lymphadenopathy in the contralateral axilla. This patient represents a diagnostic and therapeutic challenge because primary breast cancer, occult contralateral breast cancer, and extra-mammary primary lesion can all be the source of the contralateral axillary metastasis. Left breast-conserving surgery, left sentinel lymph node biopsy, right breast mass excision, and right axillary lymph node dissection were performed. Immunohistochemical analysis revealed that the left breast cancer specimen was positive for estrogen receptor (ER) and progesterone receptor (PR), but negative for human epidermal growth factor receptor 2 (HER2). In contrast, the right axillary lymphadenopathy specimen was negative for ER and PR, but positive for HER2. Further investigation revealed no evidence of occult primary cancers or extra-mammary tumors. After surgical intervention, the patient was treated with adjuvant chemotherapy, adjuvant radiation therapy, and targeted therapy with trastuzumab. Two years after diagnosis, she is free of disease and presently being treated with tamoxifen. PMID- 26668572 TI - Cetuximab Rechallenge and Monotherapy in Patients with Squamous Cell Carcinoma of the Head and Neck. AB - Smokers with squamous cell carcinoma of the head and neck (SCCHN) have a particularly poor prognosis when compared with human papillomavirus-positive SCCHN. Here, we present case reports of two smokers with SCCHN treated with cetuximab-based therapy, highlighting the potential benefit of cetuximab before definitive chemoradiotherapy in patients with poor performance status as well as cetuximab rechallenge after progression. We conclude that cetuximab demonstrated notable effectiveness in two patients at high risk for poor prognosis, yielding a durable response in one and retaining activity on rechallenge in the other. PMID- 26668573 TI - A Rare Case of an Osteoid Osteoma of the Rib Treated under Computed Tomography Guidance: A Case Report and Review of the Literature. AB - Osteoid osteoma (OO) usually occurs in the extremities of young adults. The tumor can arise in any part of the skeletal tissue; however, it is rarely found in the rib, with limited reports to date. In this report, we present a rare case of OO arising in the rib, which was successfully treated under computed tomography guidance with minimal invasiveness. At the final follow-up after 4 years, no local recurrence was observed. PMID- 26668574 TI - Lipid Cell and Micropapillary Variants of Urothelial Carcinoma of the Ureter. AB - We report on a case of urothelial carcinoma (UC) with lipid cell and micropapillary variants in the ureter. A 64-year-old man presented with gross hematuria. Urinary cytology revealed the presence of atypical urothelial cells. Computed tomography and drip infusion/retrograde pyelography identified a mass occupying lesion in the left mid-ureter, as well as left hydronephrosis. A clinical diagnosis of left ureteral cancer was given and the patient underwent left nephroureterectomy. Microscopically, the major component of the tumor was a conventional high-grade UC. In the invasive region, however, lipid cell and micropapillary variants of UC were also observed. Upon immunohistochemical analysis, all of the components were diffusely positive for cytokeratin 7 and p53. Intense membranous expression of human epidermal growth factor receptor 2 (HER2) was also observed in both the lipid cell and micropapillary variants of UC, whereas weak and incomplete staining was observed in most regions of the conventional UC. The pathological stage was pT3 N2. Multiple times, the patient experienced recurrence of the UC in the urinary bladder and urethra. Although the patient underwent total cystectomy and urethrectomy, 52 months following the initial surgery, signs of local recurrence developed, as well as multiple lymph node and bone metastases. The patient died 75 months following the initial surgery. To the best of our knowledge, this is the first reported case of a lipid cell variant of ureteral UC. The overexpression of HER2 may be associated with both the lipid cell and micropapillary variants of UC. PMID- 26668575 TI - Successful Treatment of Intracranial Germ Cell Tumor: Report of Two Unusual Cases and Literature Review. AB - Primary intracranial germ cell tumor (GCT) is a rare tumor that generally occurs due to developmental anomaly. Although intracranial GCT is sensitive to treatment, a high recurrence rate, treatment-related long-term complications and the heterogeneity of this tumor group make treatment complicated. Moreover, because of its location, hydrocephalus and visual field defect, functional disturbance of the pituitary gland can occur and require attention. Treatment primarily relies on chemotherapy and radiation therapy but the management of intracranial GCT remains unsettled, especially in the case of unusual circumstances such as multifocal tumor or nongerminomatous GCT. Here, we present two unusual cases of intracranial GCT: one case with a bifocal intracranial germinoma, and the other with an intracranial choriocarcinoma. Both cases were treated with neoadjuvant chemotherapy followed by reduced-field radiation therapy without significant treatment-related complication. Further, we performed a PubMed search to investigate the appropriate treatment strategy for this unusual subtype of intracranial GCT. PMID- 26668576 TI - Prostate Cancer: Cases of Rare Presentation and Rare Metastasis. AB - Prostate cancer is the second most common cancer in men. Diagnosis of early disease is based on prostate biopsy which is carried out because of symptoms of prostatism or asymptomatic rise in PSA. On the other side, advanced disease can locally invade and metastasise to lymph nodes, bones, lungs, etc. Initial presentation of prostate cancer in form of brain metastasis is extremely seldom. Similarly, prostate cancer, which metastasised to the breast, is very rare too. Here, we discuss two unique cases of prostate cancer, one of them had an initial presentation of brain metastasis from prostate adenocarcinoma and the other case had an established diagnosis of prostate cancer metastasised to the breast. In theory, cancer can cause metastatic spread to any part of the body; however diversity into such presentation or progression from prostate cancer has not been frequently noticed. PMID- 26668577 TI - A Case of Metastatic Urothelial Carcinoma Treated with Pemetrexed as Third-Line Chemotherapy with Discussion and Literature Review. AB - Pemetrexed is an antifolate agent that is regarded as an alternative second-line chemotherapy against advanced or metastatic urothelial carcinoma (UC). However, there is limited information on pemetrexed in a third-line setting. We report a case of metastatic UC treated with pemetrexed as third-line chemotherapy following gemcitabine and cisplatin (GC) and gemcitabine and docetaxel (GD) therapies. A 73-year-old man with a history of transurethral resection of bladder carcinoma presented with pollakiuria. CT revealed a mass in the left renal pelvis that had invaded into the parenchyma of the left kidney, as well as para-aortic and mediastinum lymph node enlargement. Urinary cytology of the lesion in the left renal pelvis revealed UC. Thus, the patient was diagnosed with left renal pelvic carcinoma (cT3N2M0). After having received 4 courses of GC therapy, another mediastinum lymph node was enlarged. He subsequently received 3 courses of GD therapy as second-line chemotherapy, which showed little efficacy against the metastatic lesions. The patient was administered 3 courses of pemetrexed as third-line chemotherapy; however, its effect on tumor reduction was not sufficient. Finally, metastasis to the liver was observed, and he died 21 months after initiation of chemotherapy. For pathological confirmation, needle biopsy of a metastatic lymph node performed after death revealed high-grade UC and a high positivity of programmed death ligand 1 (PD-L1) in the tumor, which suggested that he could have benefited from anti-PD-L1 antibody immunotherapy. This report describes the outcome of pemetrexed treatment and proposes another possible candidate as third-line chemotherapy against metastatic UC. PMID- 26668578 TI - Rare Association of Perivascular Granulomatous Lesions in a Patient with Acute Retinal Necrosis. AB - PURPOSE: The aim of this study was to examine sequential changes in perivascular granulomatous lesions with acute retinal necrosis (ARN). METHODS: A healthy 46 year-old Japanese woman, who developed floaters and pain in her left eye, underwent optical coherence tomography (OCT), fluorescein angiography, and routine ophthalmological examinations. Treatment-associated changes in perivascular granulomatous lesions were monitored using spectral-domain (SD)-OCT. RESULTS: The patient had no previous ophthalmic history, and her general condition was good. A slit-lamp examination revealed keratic precipitates and aqueous cells (2+) in the left eye. A fundus examination showed yellow-white patches of necrotizing retinal lesions in the temporal upper area, retinal arteritis, retinal hemorrhage, and vitreous opacities. The patient was diagnosed with ARN according to diagnostic criteria. SD-OCT images confirmed high-intensity and uniform granulomatous deposits in the perivascular area and fovea. Systemic corticosteroids and antiviral therapy were initiated, resulting in the gradual resolution of granulomatous lesions. The patient continues to be followed untreated without evidence of recurrence, retinal detachment, or active inflammation. CONCLUSIONS: This is the first report of perivascular granulomatous lesions in a patient with ARN. Our results showed that the formation of granulomas may be induced in the retina of ARN patients without fulminant inflammation. PMID- 26668579 TI - A Case of Mature Natural Killer-Cell Neoplasm Manifesting Multiple Choroidal Lesions: Primary Intraocular Natural Killer-Cell Lymphoma. AB - PURPOSE: Natural killer (NK) cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK cell neoplasm in which the eye was considered to be the primary organ. CASE: A 50 year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. CONCLUSIONS: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease. PMID- 26668580 TI - CC-chemokine receptor 7 and its ligand CCL19 promote mitral valve interstitial cell migration and repair. AB - The effect of CC-chemokine receptor 7 (CCR7) and CC-chemokine ligand 19 (CCL19) on rheumatic mitral stenosis is unknown. This study aimed to explore the roles of CCR7 and CCL19 in rheumatic mitral stenosis by measuring the expression of CCR7 and CCL19 in human mitral valves from rheumatic mitral stenosis patients. Additionally, we examined their effects on human mitral valve interstitial cells (hMVICs) proliferation, apoptosis and wound repair. CCR7 and CCL19 expression was measured in the mitral valves from rheumatic mitral stenosis patients (n = 10) and compared to normal mitral valves (n = 5). CCR7 was measured in cultured hMVICs from rheumatic mitral stenosis patients and normal donors by RT-PCR and immunofluorescence. The cells were also treated with exogenous CCL19, and the effects on wound healing, proliferation and apoptosis were assayed. In the rheumatic mitral valves, valve interstitial cells expressed CCR7, while mononuclear cells and the endothelium expressed CCL19. Healthy mitral valves did not stain positive for CCR7 or CCL19. CCR7 was also detected in cultured rheumatic hMVICs or in normal hMVICs treated with CCL19. In a wound healing experiment, wound closure rates of both rheumatic and normal hMVICs were significantly accelerated by CCL19. These effects were abrogated by a CCR7 neutralizing antibody. The CCR7/CCL19 axis did not influence the proliferation or apoptosis of hMVICs, indicating that wound healing was due to increased migration rates rather than increased proliferation. In conclusion, CCR7 and CCL19 were expressed in rheumatic mitral valves. The CCR7/CCL19 axis may regulate remodeling of rheumatic valve injury through promoting migratory ability of hMVICs. PMID- 26668581 TI - Effect of burden and origin sites of premature ventricular contractions on left ventricular function by 7-day Holter monitor. AB - Recent studies have shown that premature ventricular contractions (PVCs) could enlarge the heart, but its risk factors are incompletely understood as a single 24-hour recording cannot reflect the true PVC burden due to day-to-day variability. Our purpose was to investigate the effect of burden and origin sites on left ventricular (LV) function in patients with PVCs by 7-day Holter electrocardiography (ECG). From May 2012 to August 2013, 112 consecutive patients with PVCs were recruited from the authors' affiliated hospital. All patients received 2-dimensional transthoracic echocardiography, 12-lead routing ECG and 7 days Holter ECG. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured. A total of 102 participants with PVCs were included in the final analysis. Origin of PVCs from the tricuspid annulus had the highest burden and NT-proBNP level. LV papillary muscle had a higher LV ejection fraction (EF) level and a lower LV end-systolic dimension (ESD) than other PVC foci (P<0.05). The high burden group had a higher LV end-diastolic dimension (EDD) and LVESD but lower LVEF than the other two groups (P<0.05). Female, older age, physical work, and history of PVCs had a significantly positive correlation with symptoms. Male, older age, physical work, and high burden were positive predictors of enlarged LVEDD, LVESD and higher serum NT-proBNP level, but lower LVEF. Seven-day dynamic ECG Holter monitor showed the true PVC burden on patients with PVCs. PVCs with a lower burden or origin from the LV papillary muscle and the fascicle were relatively benign, while PVCs with a higher burden or origin from the tricuspid annulus may lead to cardiac dysfunction. PMID- 26668582 TI - Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients: a meta-analysis of randomized controlled trials. AB - We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies (11 articles) with a total of 42,892 patients (20,491 patients in the ACEI/ARBs group and 22,401 patients in the beta-blocker or the calcium antagonist group) met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation (AF) recurrence compared to calcium antagonists (RR = 0.48; 95%CI, 0.40-0.58; P<0.00001) or beta-blockers (RR = 0.39; 95%CI, 0.20-0.74; P = 0.005) in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of congestive heart failure (RR = 0.86; 95%CI, 0.77-0.96; P = 0.007). However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects. PMID- 26668583 TI - A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1. AB - Non-obstructive azoospermia (NOA) is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci (eQTL) of FAM160B1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM160B1 was reduced for the homozygous alternate genotype (GG) of rs7099208, but not for the homozygous reference or heterozygous genotypes. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round spermatids. From 17 patients with NOA and five with obstructive azoospermia (OA), immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1. PMID- 26668584 TI - Neuroanatomy and clinical analysis of the cervical sympathetic trunk and longus colli. AB - Anterior cervical surgery is commonly used for cervical vertebral body lesions. However, the structure of blood vessels and nerve tissues along the route of anterior cervical surgery is complex. We aimed to measure the data of the longus colli, the sympathetic trunk and the cervical sympathetic trunk (CST) ganglia in Chinese cadaver specimens. A total of 32 adult cadavers were studied. We delineated the surgical anatomy of the CST. The superior and inferior/cervicothoracic ganglia of the sympathetic trunk consistently appeared. The middle ganglion was observed in 28.1% of the specimens and there were 2 cases of unilateral double middle cervical ganglia. The inferior ganglion was observed in 25.0% of the specimens and the cervicothoracic ganglion was observed in the remaining specimens. The distance between the CST gradually decreased from the top to the bottom, and the distance between the medial edges of the longus colli gradually broadened from the top down. The average angle between the bilateral CST and the midline of the vertebra was 11.2 degrees +/-1.8 degrees on the left side and 10.3 degrees +/-1.4 degrees on the right side. The average angle between the medial margins of longus colli of both sides was 11.1 degrees +/-1.9 degrees . The CST is at high risk when LC muscle is cut transversely or is dragged heavily, especially at the levels of C6 and C7. Awareness of the regional anatomy of the CST could help surgeons to identify and preserve it during anterior cervical surgeries. PMID- 26668585 TI - An Aggravated Trajectory of Depression and Anxiety Co-morbid with Hepatitis C: A Within-groups Study of 61 Australian Outpatients. AB - BACKGROUND: This study aimed to explore the course of depression and anxiety in chronic hepatitis C patients. METHODS: Data were combined from two studies: (1) Hospital Anxiety and Depression Scale (HADS) scores in 395 consecutive Australian outpatients from 2006 to 2010 formed the baseline measurement; and (2) Depression Anxiety Stress Scales (DASS) scores in a survey of a sub-sample of these patients in 2011 formed the follow-up measurement. After converting DASS to HADS scores, changes in symptom scores and rates of case-ness (>=8), and predictors of follow up symptoms were assessed. RESULTS: Follow-up data were available for 61 patients (70.5% male) whose age ranged from 24.5 to 74.6 years (M=45.6). The time to follow-up ranged from 20.7 to 61.9 months (M=43.8). Baseline rates of depression (32.8%) and anxiety (44.3%) increased to 62.3% and 67.2%, respectively. These findings were confirmed, independent of the conversion, by comparing baseline HADS and follow-up DASS scores with British community norms. Baseline anxiety and younger age predicted depression, while baseline anxiety, high school non-completion, and single relationship status predicted anxiety. CONCLUSION: This study demonstrated a worsening trajectory of depression and anxiety. Further controlled and prospective research in a larger sample is required to confirm these findings. PMID- 26668587 TI - Corrigendum. AB - [This corrects the article DOI: 10.1177/1756285615585918.]. PMID- 26668586 TI - Biomechanical analysis of spasticity treatment in patients with multiple sclerosis. AB - OBJECTIVES: New metrics for clinical spasticity are needed to assess motor performance, since scales such as the Ashworth and Tardieu are unreliable. Here, we assessed outcomes of baclofen treatment in patients with multiple sclerosis (MS) using biomechanical analysis of voluntary movements. METHODS: Patients with MS and symptomatic limb spasticity were recruited for a pre-post baclofen titration study, along with age-matched healthy controls. Oral baclofen was titrated to optimize spasticity symptoms in all MS cases over 4 weeks. Clinical assessments included the Modified Ashworth Scale (MAS), Tardieu Scale (TS); elbow kinematics were measured via the Transient Acceleration Measurement Interface (TAMI); performance was measured as the score at 4 weeks minus the baseline score in all measures. Movement proficiency within TAMI was quantified through a scale free smoothness measure, according to the regional excursion deviation (RED) from a constant-velocity approximant. RESULTS: Twelve patients with MS [age: 47.8 +/- 9.8 years; women: 4; disease duration: 20 +/- 10 years; disease-modifying therapy use: 7; Expanded Disability Status Scale (EDSS): 6.8 +/- 1.4] and eight age matched healthy controls were evaluated concurrently (mean age: 49.5 +/- 13.1 years; women = 3). In MS cases, no significant improvement in arm spasticity was observed with main effects: MAS: -41.6 +/- 72.6 (p = 0.09); EDSS: -1.6 +/- 10.4% (p = 0.49); and TS: -8.3 +/- 2.1% (p = 0.32), -24.9 +/- 63.6% (p = 0.42), and 30.7 +/- 79.9% (p = 0.06), at slow, moderate, and fast speeds, respectively. However, voluntary motion smoothness, as measured by TAMI: RED, decreased significantly: 0.62 +/- 0.08 versus 0.54 +/- 0.09, p < 0.001, indicating significant increase in movement smoothness post treatment. CONCLUSION: A simple biomechanical analysis of voluntary movements revealed a significant reduction of spasticity after 30 days of baclofen therapy in patients with MS that was not detected by clinical assessments. PMID- 26668588 TI - Novel antiepileptic drug lacosamide exerts neuroprotective effects by decreasing glial activation in the hippocampus of a gerbil model of ischemic stroke. AB - Lacosamide, which is a novel antiepileptic drug, has been reported to exert various additional therapeutic effects. The present study investigated the neuroprotective effects of lacosamide against transient cerebral ischemia-induced neuronal cell damage in the hippocampal cornu ammonis (CA)-1 region of a gerbil model. Neuronal Nuclei immunohistochemistry demonstrated that pre- and post surgical treatment (5 min ischemia) with 25 mg/kg lacosamide protected CA1 pyramidal neurons in the lacosamide-treated-ischemia-operated group from ischemic injury 5 days post-ischemia, as compared with gerbils in the vehicle-treated ischemia-operated group. Furthermore, treatment with 25 mg/kg lacosamide markedly attenuated the activation of astrocytes and microglia in the ischemic CA1 region at 5 days post-ischemia. The results of the present study suggested that pre- and post-surgical treatment of the gerbils with lacosamide was able to protect against transient cerebral ischemic injury-induced CA1 pyramidal neuronal cell death in the hippocampus. In addition, the neuroprotective effects of lacosamide may be associated with decreased activation of glial cells in the ischemic CA1 region. PMID- 26668589 TI - Effects of acute exercise on liver function and blood redox status in heavy drinkers. AB - Excessive alcohol consumption can induce oxidative stress, resulting in the development of several diseases. Exercise has been reported to prevent and/or improve a number of health issues through several mechanisms, including an improvement in redox status. It has also been previously suggested that exercise can help individuals with alcohol use disorders reduce their alcohol intake; however, research in this field is limited. The aim of the present study was to investigage the effects of acute exercise of moderate intensity on the liver function and blood redox status in heavy drinkers. For this purpose, a total of 17 heavy drinkers [age, 31.6+/-3.2 years; body mass index (BMI), 27.4+/-0.8 kg/m2; experimental group (EG)] and 17 controls [age, 33.5+/-1.3 years; BMI, 26.1+/-1.4 kg/m2; control group (CG), who did not exceed moderate alcohol consumption], underwent one trial of acute exercise of moderate intensity (50-60% of the heart rate reserve) for 30 min on a cycle ergometer, following an overnight fast, and abstaining from smoking and alcohol consumption. Blood samples were obtained before and immediately after exercise for later determination of the indices of liver function and blood redox status. The subjects in the EG had significantly higher (p<0.05) baseline gamma-glutamyl transferase (gamma-GT) levels compared to the subjects in the CG. Exercise thus resulted in significantly higher gamma-GT levels (p<0.005) only in the EG. No significant differences in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) baseline levels were observed between the 2 groups. Following exercise, the AST levels increased significantly (p<0.001) in both groups, whereas the ALT levels increased significantly (p<0.01) only in the EG. The baseline glutathione (GSH) levels were significantly lower (p<0.05) and remained low following exercise in the EG. In addition, we observed a trend for higher (p=0.07) baseline levels of thiobarbituric acid-reactive substances (TBARS), which remained elevated post-exercise in the EG compared to the CG. Significantly increased post-exercise total antioxidant capacity (TAC; p<0.01) and uric acid (UA; p<0.05) levels were noted in the CG, whereas the TAC (p=0.06) and UA (p=0.08) levels increased and approached significance post-exercise in the EG. No significant differences in the baseline levels of total bilirubin and protein carbonyl were observed between the 2 groups, even post-exercise. Thus, the findings of the present study indicate that even though heavy drinkers may be prone to oxidative stress, their exercise-induced antioxidant response is similar to that of individuals who do not drink heavily. PMID- 26668590 TI - Surgical methods and efficacies for cervicothoracolumbar spinal schwannoma. AB - The aim of this study was to investigate the surgical methods and efficacies for cervicothoracolumbar spinal schwannoma (CSS). A total of 52 patients who had undergone treatment for schwannoma were retrospectively analyzed. Two methods were employed for the surgical resection of the thoracic and lumbar schwannomas: Type I (posterior midline approach semi-laminectomy with tumor resection and internal fixation with pedicle screws) was used in 24 cases, and type II (posterior midline approach laminectomy with tumor resection and internal fixation with pedicle screws) was used in 26 cases. Two cases of giant cervical schwannoma were treated via anterior-posterior combined surgery. Histopathological examination confirmed the diagnosis of schwannoma in all cases (n=52). The clinical status of the patients was evaluated pre- and postoperatively using the visual analog scale, Oswestry Disability Index and Japanese Orthopedic Association scale, and the scores associated with the two types of surgical method were compared. Within the follow-up period, which lasted between 6 months and 3 years, no recurrence was detected, and such preoperative symptoms as radicular pain and spinal dysfunction were improved significantly. The numbness and hyperesthesia were relieved to different extents. In conclusion, methods of exposing and surgically treating CSS should be selected according to the growth site of the schwannoma in order to reduce the blood loss and surgery duration and to improve the surgical safety. PMID- 26668591 TI - Effect of peritoneal lavage with ulinastatin on the expression of NF-kappaB and TNF-alpha in multiple organs of rats with severe acute pancreatitis. AB - The aim of the present study was to investigate the effect of peritoneal lavage with ulinastatin on the expression levels of nuclear factor kappaB (NF-kappaB) and tumor necrosis factor (TNF)-alpha in multiple organs of rats with severe acute pancreatitis (SAP). Male Wistar rats were randomly divided into the following groups: Sham-operated (C), SAP model (SAP), saline lavage (SL), intravenous ulinastatin (IU) and peritoneal lavage with ulinastatin (UL). The SAP model was induced by the retrograde infusion of 5% sodium taurocholate into the biliopancreatic ducts of the rats. Intraperitoneal lavage or injection was performed immediately following the establishment of the SAP model in groups SL, IU and UL. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. The survival time of half of the rats in each group was recorded over a 12-h period. At 3 h after the induction of SAP, inflammatory mediators and the expression levels of NF-kappaB and TNF-alpha in multiple organs of the rats in each group were also detected. The survival rates of the rats in group UL at 6 h and 9 h were increased compared with those in group SAP, and were also higher than that in groups SL and IU. The levels of serum inflammatory mediators were effectively reduced in groups SL, IU and UL, the greatest effects were observed in group UL. The expression levels of NF-kappaB and TNF-alpha in multiple organs were significantly lower in group UL compared with other groups. Intraperitoneal lavage with ulinastatin significantly ameliorated the inflammatory reaction and inhibited NF-kappaB and TNF-alpha expression in multiple organs of SAP model rats. PMID- 26668592 TI - Establishment of a rat model for osteoarthritis resulting from anterior cruciate ligament rupture and its significance. AB - The purpose of this study was to examine the establishment of a model concerned with osteoarthritis resulting from the anterior cruciate ligament rupture of rats and investigate the associated mechanism, as well as provide a theoretical basis for clinical treatment of the disease. Forty Sprague-Dawley male rats were randomly divided into two groups of 20 rats each and the anterior cruciate ligament transaction model and knee joint brake model were successfully established. Two rats in the anterior cruciate ligament transection group (10%) and 3 rats in the knee joint brake group (15.0%) died. The survival rate of the two groups was not statistically significant (chi2<0.001, P=1.000). Swelling of the knee joint and synovium of rats in the two experimental groups was aggravated. The Mankin score was significantly higher in the anterior cruciate ligament transection group than that in the experimental group and the difference was statistically significant (P<0.05). By contrast, no significant difference was observed for osteoarthritis severity for the two experimental groups (P>0.05). Analysis of the subgroups showed that the proportion of the anterior cruciate ligament in the experimental group was significantly higher than that of the knee joint brake group, and the difference was statistically significant (P<0.05). By contrast, the difference was not statistically significant in the comparison of the medium and early proportion (P>0.05). The content of protein polysaccharide and II collagen fiber in the experimental group of the anterior cruciate ligament transection was lower than that of the knee joint brake group, and this difference was statistically significant (P<0.05). Thus the mechanism of osteoarthritis may be associated with the decrease in the content of protein and II collagen fibers. PMID- 26668593 TI - Endogenous carbon monoxide downregulates hepatic cystathionine-gamma-lyase in rats with liver cirrhosis. AB - The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on the hydrogen sulfide/cystathionine-gamma-lyase (H2S/CSE) pathway in cirrhotic rat livers. The rats were allocated at random into four groups: Sham, cirrhosis, cobalt protoporphyrin (CoPP) and zinc protoporphyrin IX (ZnPP). The expression of hepatic CSE mRNA was evaluated using a quantitative polymerase chain reaction, while CSE protein expression was determined using immunohistochemical analysis. Hematoxylin and eosin staining was performed for the histological evaluation of liver fibrosis. The levels of H2S, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in the arterial blood were determined, in addition to the portal vein pressure. The mRNA and protein expression levels of hepatic CSE and the serum levels of H2S were significantly decreased in the cirrhosis group compared with those in the sham group (P<0.05). Compared with the cirrhosis group, rats in the ZnPP group had significantly lower levels of serum ALT, AST and TBIL, arterial COHb and hepatic fibrosis, while hepatic CSE expression and the production of H2S were significantly increased (P<0.05). The CoPP group exhibited decreased hepatic CSE expression and H2S production, but aggravated hepatic function and fibrosis (P<0.05). In conclusion, the H2S/CSE pathway is involved in the formation of liver cirrhosis and serves a crucial function in protecting liver cells against the progression of liver fibrosis. Endogenous CO downregulates hepatic CSE mRNA and protein expression and the production of H2S in rats with liver cirrhosis. PMID- 26668594 TI - Advantages of a dual-color fluorescence-tracing glioma orthotopic implantation model: Detecting tumor location, angiogenesis, cellular fusion and the tumor microenvironment. AB - Various organs of the body have distinct microenvironments with diverse biological characteristics that can influence the growth of tumors within them. However, the mechanisms underlying the interactions between tumor and host cells are currently not well understood. In the present study, a dual-color fluorescence-tracing glioma orthotopic implantation model was developed, in which C6 rat glioma cells labeled with the red fluorescent dye CM-Dil, and SU3 human glioma cells stably expressing red fluorescence protein, were inoculated into the right caudate nucleus of transgenic female C57BL/6 nude mice expressing enhanced green fluorescent protein. The dual-color tracing with whole-body in vivo fluorescence imaging of xenografts was performed using a live imaging system. Frozen sections of the transplanted tumor were prepared for histological analyses, in order to detect the presence of invading tumor cells, blood vessels and cellular fusion. Dual-color images were able to distinguish between red tumor cells and green host cells. The results of the present study suggested that a dual-color fluorescence-tracing glioma orthotopic implantation model may be convenient for detecting tumor location, angiogenesis, cellular fusion, and the tumor microenvironment. PMID- 26668595 TI - Hyperosmotic stress induces cisplatin sensitivity in ovarian cancer cells by stimulating aquaporin-5 expression. AB - Aquaporins (AQPs) are important mediators of water permeability and are closely associated with tumor cell proliferation, migration, angiogenesis and chemoresistance. Moreover, the chemosensitivity of tumor cells to cisplatin (CDDP) is potentially affected by osmotic pressure. The present study was undertaken to determine whether hyperosmosis regulates ovarian cancer cell sensitivity to CDDP in vitro and to explore whether this is associated with AQP expression. The hyperosmotic stress was induced by D-sorbitol. 3AO ovarian cancer cells were treated with different concentrations of hypertonic medium and/or CDDP for various times, followed by measuring the inhibition rate of cell proliferation using an MTT assay. In addition, AQP expression in response to osmotic pressure and/or CDDP was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation in response to hypertonic stress was also measured when AQP5 was knocked down by small interfering (si)RNA. 3AO cell proliferation was inhibited by hyperosmotic stress, while the expression of AQP5, but not that of AQP1, AQP3 or AQP9, was increased in a dose- and time-dependent manner in hypertonic sorbitol-containing medium. When AQP5 was silenced by siRNA, cells were susceptible to hypertonic stress. MTT analyses showed that the inhibition of cell proliferation by a low dose of CDDP increased significantly with exposure to a hyperosmotic stimulus, and this effect was reduced when a high dose of CDDP was used. AQP5 expression was induced by a low dose of CDDP, but was reduced by a high dose of CDDP. However, hyperosmosis enhanced AQP5 mRNA expression at every dose of CDDP tested, compared with isotonic medium. With prolonged treatment time, AQP5 expression was reduced by CDDP in hypertonic and isotonic culture medium. Thus, the effects of hyperosmosis on cell sensitivity to CDDP were associated with AQP5 expression. These results suggest that AQP5 expression in ovarian cancer cells is induced by hypertonic medium, and that the sensitivity of ovarian cancer cells to CDDP can be regulated by hyperosmosis associated with AQP5 expression. PMID- 26668596 TI - Neuroprotective effects of Rhizoma Dioscoreae polysaccharides against neuronal apoptosis induced by in vitro hypoxia. AB - Rhizoma Dioscoreae polysaccharides (RDPS) are the primary active ingredient of Rhizoma Dioscoreae, which is a traditional Chinese medicine. RDPS have previously been shown to scavenge reactive oxygen species, and protect against D-galactose induced mimetic aging. The present study aimed to investigate the neuroprotective effects of RDPS against hypoxia-induced neuronal cell apoptosis. Neuronal cells harvested from pregnant Sprague-Dawley rats were divided into groups, as follows: i) Normal control group; ii) hypoxia-induced apoptosis neuronal cell model; iii) 0.025 g/l RDPS-treated group; iv) 0.05 g/l RDPS-treated group; v) 0.1 g/l RDPS treated group; and vi) 0.25 g/l RDPS treated group. Neuronal cell viability was investigated using an MTT assay, and neuronal cell apoptosis was analyzed using Annexin V-fluorescein isothiocyanate/propidium iodide double-staining, Hoechst 33342 fluorescent staining, Rhodamine 123 staining, polymerase chain reaction and immunocytochemical staining. The RDPS-treated neuronal cells exhibited improved viability, and decreased hypoxia-induced mitochondrial injury and apoptosis. In addition, the mRNA and protein expression levels of caspase-3 and B-cell lymphoma (Bcl)-2-associated X protein (Bax) were significantly downregulated, whereas the mRNA and protein expression levels of Bcl-2 were significantly upregulated, in the RDPS-treated hypoxic neurons, as compared with the apoptosis model (P<0.05). Furthermore, the ratio of Bcl-2 expression:Bax expression significantly increased following RDPS treatment, as compared with the apoptosis model (P<0.05). The results of the present study suggested that RDPS may attenuate hypoxia-induced neuronal cell apoptosis by altering the expression levels of key apoptosis regulating proteins in hypoxic neurons. PMID- 26668597 TI - Isolation and characterization of side population cells from the human ovarian cancer cell line SK-OV-3. AB - Ovarian cancer (OC) is the most malignant type of gynecological tumor due to its high recurrence rate following initial treatment. Previous studies have indicated that cancer stem cells (CSCs) may be a potential cause underlying the high proportion of recurrence. Side population (SP) cells isolated from cancer cell lines have been shown to exhibit characteristics associated with CSCs, but studies on SP cells in human ovarian SK-OV-3 cell line are limited. In the present study, the SP cell fraction (4.83% of the total cell population) was isolated using flow cytometry, and analyzed by immunocytochemical analysis and reverse transcription-quantitative polymerase chain reaction. The results showed that SP cells exhibited a high mean fluorescence intensity for CD44, a CSC marker, in addition to elevated expression of the CSCs-associated genes, ATP binding cassette sub-family G member 2 and Nestin. These findings indicated the stem cell-like features of the SP cells. Furthermore, a colony formation test showed that the isolated SP cells possessed a marked capacity for self regeneration and proliferation. In addition, a cell cycle assay involving cisplatin indicated that the SP cells were strongly resistant to chemotherapy. In conclusion, the present results suggested that SP cells isolated from the SK-OV-3 cell line exhibited properties typically associated with CSCs. Therefore, the isolated SP cells may be used to provide novel insight into potential therapies against OC. PMID- 26668598 TI - Effect of 131I 'clear residual thyroid tissue' after surgery on the function of parathyroid gland in differentiated thyroid cancer. AB - Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) 'clear residual thyroid tissue' following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I 'clear residual thyroid tissue' treatment and underwent a whole body scan after 1 week to determine whether 'clear residual thyroid tissue' treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8+/-0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I 'clear residual thyroid tissue' treatment did not significantly impair the parathyroid function, thereby improving the treatment effect. PMID- 26668599 TI - Simultaneous integrated dose reduction intensity-modulated radiotherapy applied to an elective nodal area of limited-stage small-cell lung cancer. AB - The purpose of this study was to evaluate the clinical efficacy and toxicity of simultaneous integrated dose reduction intensity-modulated radiotherapy (SIR IMRT) applied to an elective nodal area of patients with limited-stage small-cell lung cancer (LS-SCLC). Between January 2010 and March 2013, 52 patients with LS SCLC that was treated with SIR-IMRT were retrospectively analyzed. A radiation dose of 54 Gy was administered in 30 fractions (1.8 Gy/fraction) to the planning target volume (PTV). Simultaneously, 60 Gy was administered in 30 fractions (2 Gy/fraction) to the planning gross tumor volume. Radiation-related toxicities were estimated according to the Common Terminology Criteria for Adverse Events (version 3.0). Overall survival (OS), locoregional recurrence-free survival and progression-free survival were estimated using the Kaplan-Meier method. By the last follow-up, the median follow-up time was 16.5 months, the median OS was 24.0 months, and 21 (40.4%) patients had experienced treatment failure. Of these patients, 5 (9.6%) patients developed in-field recurrence (within the 95% isodose curve of the PTV) and 1 (1.9%) patient developed an out-of-field recurrence (not a distant metastasis). Grade 3 or higher treatment-related pneumonia was observed in 4/52 (7.6%) patients, and grade 3 radiation-related esophagitis was experienced by 2/52 (3.8%) patients. The results of this preliminary study suggest that SIR-IMRT is safe and effective for patients with LS-SCLC and should be further evaluated in a large prospective clinical trial. PMID- 26668600 TI - E-cadherin expression in a rat model of acute pancreatitis. AB - A clinical requirement exists for early biomarkers that can predict the severity of acute pancreatitis (AP). In order to determine whether E-cadherin is associated with the severity of AP, a pancreatitic rat model was established and the expression levels of E-cadherin were detected. A study population of 24 Sprague Dawley rats was administered intraperitoneal injections of various concentrations of L-arginine in order to induce pancreatitis. Rats were assigned to the severe acute pancreatitis (SAP) or mild acute pancreatitis (MAP) group based on the results of histological evaluations and the serum levels of amylase. An additional 8 rats received intraperitoneal injections of NaCl solution, as a control group. For each group, the serum concentrations of soluble E-cadherin and the expression levels of E-cadherin protein in the pancreatic tissue were detected. The results indicated that the rat model of pancreatitis was successfully established. Rats in the high concentration L-arginine treatment group, which exhibited a higher pancreatitis pathology score and level of serum amylase, were assigned to the SAP group. Low concentration L-arginine group rats were assigned to the MAP group. The pathology scores and levels of serum amylase in the SAP and MAP group rats were higher compared with the control group rats. The levels of serum E-cadherin were the most elevated in the SAP group. Statistically significant differences were detected in the SAP and MAP groups compared with the control group, and in the SAP group compared with the MAP group (P<0.05). Furthermore, the levels of E-cadherin protein in the pancreatic tissue were elevated in the SAP group compared with the MAP and control groups. In conclusion, the present study demonstrated that E-cadherin was overexpressed in SAP rats, and the overexpression of E-cadherin may be associated with the severity of AP. PMID- 26668601 TI - Impact of collection, isolation and storage methodology of circulating microvesicles on flow cytometric analysis. AB - Microvesicles (MVs) in body fluids participate in a variety of physical and pathological processes, and are regarded as potential biomarkers for numerous diseases. Flow cytometry (FCM) is among the most frequently used techniques for MV detection. However, different handling methods unavoidably cause pre analytical variations in the counts and sizes of MVs determined by FCM. The aim of the present study was to investigate the effect of centrifugation, storage conditions and anticoagulant on MV measurements. Blood samples were obtained from 13 healthy donors, including 4 women and 9 men. Calcein-AM staining was used to label MVs and assess the impact of pre-analytical preparation, including centrifugation, and storage conditions on MV measurements obtained using FCM. The range of factors investigated for comparison included: Platelet-free plasma (PFP) stored at -80 degrees C for 1 or 4 weeks; MVs stored at 4 degrees C for 3-4 days or 1 week; MVs frozen at -80 degrees C for 1 or 4 weeks; and anticoagulants, either heparin or ethylenediaminetetraacetic acid (EDTA). No statistically significant differences in MV counts were detected between the two centrifugation speeds (16,000 and 20,500 * g) or among the three centrifugation times (15, 30 and 60 min) investigated. Similarly, no significant differences were noted in MV counts between the two anticoagulants tested (heparin and EDTA). However, the storage of PFP or MVs in heparin-anticoagulated plasma for different periods markedly affected the detected MV counts and size distribution. The counts and sizes of MVs from EDTA-anticoagulated plasma were only affected when the MVs were frozen at -80 degrees C for 4 weeks. In conclusion, calcein-AM is able to efficiently identify MVs from plasma and may be an alternative to Annexin V for MV staining. EDTA preserves the MV counts and size more accurately compared with heparin under calcein-AM staining. PFP centrifuged at 16,000 * g for 15 min is sufficient to isolate MVs, which enables the batch processing of samples. PFP, rather than MVs alone, appears to be the preferable mode of sample storage, as MVs stored in PFP were less affected by storage temperature and duration. The present study provides a methodology for MV collection, storage and isolation, to facilitate further investigation of MVs as biomarkers in disease. PMID- 26668602 TI - In vitro gene expression profile of bovine peripheral blood mononuclear cells in early Mycobacterium bovis infection. AB - The intracellular parasite Mycobacterium bovis (M. bovis) causes tuberculosis in cattle and humans. Understanding the interactions between M. bovis and host cells is essential in developing tools for the prevention, detection, and treatment of M. bovis infection. Gene expression profiles provide a large amount of information regarding the molecular mechanisms underlying these interactions. The present study analyzed changes in gene expression in bovine peripheral blood mononuclear cells (PBMCs) at 0, 4 and 24 h following exposure to M. bovis. Using bovine whole-genome microarrays, a total of 420 genes were identified that exhibited significant alterations in expression (>=2-fold). Significantly enriched genes were identified using the Kyoto Encyclopedia of Genes and Genomes database, of which the highest differentially expressed genes were associated with the immune system, signal transduction, endocytosis, cellular transport, inflammation, and apoptosis. Of the genes associated with the immune system, 84.85% displayed downregulation. These findings support the view that M. bovis inhibits signaling pathways of antimycobacterial host defense in bovine PBMCs. These in vitro data demonstrated that molecular alterations underlying the pathogenesis of tuberculosis begin early, during the initial 24 h following M. bovis infection. PMID- 26668603 TI - Enhanced expression of glucose-regulated protein 78 correlates with malondialdehyde levels during the formation of liver cirrhosis in rats. AB - The aim of the present study was to explore the role of glucose-regulated protein 78 (GRP78) in the development of liver cirrhosis promoted by intestinal endotoxemia in rats. Fifty-one male Wistar rats were randomly divided into the liver cirrhosis 4-week, 6-week and 8-week groups and the normal control group at each time point. Liver cirrhosis was induced by employing multiple pathogenic factors in the rats. Blood and liver tissues were collected. The levels of alanine aminotransferase (ALT), homocysteine, endotoxin and tumor necrosis factor alpha (TNF-alpha) in the plasma, and TNF-alpha, malondialdehyde (MDA) and procollagen type III peptide (PIIIP) in the liver tissues were determined. The mRNA and protein expression levels of GRP78 in the liver were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Morphological changes were observed through hematoxylin and eosin and van Gieson staining of the liver. Liver cirrhosis caused marked histopathological changes to the livers of the rats. Following significant increases in the levels of ALT, homocysteine, endotoxin and TNF-alpha in the plasma, and TNF-alpha, MDA and PIIIP in the liver tissues of all experimental groups with the progression of liver cirrhosis, the mRNA and protein expression levels of GRP78 also gradually increased. In addition, correlation analysis indicated that the enhanced expression of GRP78 correlated with the MDA levels of the rats during the formation of liver cirrhosis. PMID- 26668604 TI - The use of fluorine-18 fluorodeoxyglucose positron emission tomography for imaging human motor neuronal activation in the brain. AB - The present study aimed to visualize human motor neuronal activation in the brain using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), and to develop an FDG-PET procedure for imaging neuronal activation. A male volunteer underwent 20 min periods of rest and motor activation, whilst being assessed using FDG-PET on two consecutive days. The motor task, which involved repetitively grasping and releasing the right hand, was performed during the initial 5 min of the activation period. Subtraction of the rest period signal from the activation PET images was performed using the subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging method. The subtracted image detected activation of the contralateral (left) primary motor cortex, supplementary motor area, and ipsilateral (right) cerebellum. In the present study, FDG-PET detected significantly increased motor associated activation of the brain in a subject performing a motor task. PMID- 26668605 TI - Mesenchymal stem cells attenuate acute ischemia-reperfusion injury in a rat model. AB - Ischemia-reperfusion injury (IRI) following lung transplantation is associated with increased pulmonary inflammatory responses during reperfusion. Mesenchymal stem cells (MSCs) may be able to modulate inflammatory responses in IRI. The aim of the present study was to evaluate the beneficial effects of an intravenous infusion of bone marrow-derived MSCs (BMSCs) in a rat model of pulmonary IRI. IRI was induced in male Lewis rats by 1-h ischemia followed by 2-h reperfusion. The rats received phosphate-buffered saline (PBS) or BMSC infusion at the onset of reperfusion. Pulmonary injury was determined based on the mean blood oxygenation, lung edema and vascular permeability, and performing histopathological examination. Pulmonary inflammation was also evaluated through the examination of the levels of inflammatory cytokines. Compared with the PBS infusion, the BMSC infusion significantly preserved lung function, reduced lung edema and pulmonary microvascular permeability, and decreased the total injury score in rats with IRI. The mRNA levels of the pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6, were significantly reduced, while the expression of anti-inflammatory cytokine IL-10 was increased in the rats receiving BMSC infusion. The levels of cytokine-induced neutrophil chemoattractant-1, IL-1beta, and TNF-alpha in bronchoalveolar lavage fluid were also markedly reduced following BMCS infusion. In conclusion, the present results suggested that BMSC infusion exerts protective effects against pulmonary IRI by alleviating IRI-induced inflammation. These findings provide experimental evidence for the treatment of pulmonary IRI using BMSC cell therapy. PMID- 26668606 TI - Expression levels of vascular endothelial cell growth factor and microRNA-210 are increased in medulloblastoma and metastatic medulloblastoma. AB - The present study aimed to investigate the roles of the vascular endothelial cell growth factor (VEGF) and micro (mi)RNA-210 in the metastasis of primary medulloblastoma (MB) tumors. A total of 86 adult patients diagnosed with cerebellar MB were enrolled in the present study, of which 11 patients had metastatic MB in the subarachnoid space. The following samples were collected: MB primary tumor tissue, MB secondary tumor tissue, tumor adjacent tissues and cerebrospinal fluid (CSF). Immunohistochemical analyses of the tissue samples were conducted in order to detect patterns of VEGF expression. In addition, the expression levels of VEGF mRNA and miRNA-210 were analyzed using reverse transcription-quantititative polymerase chain reaction, and western blot analyses were used to investigate VEGF protein expression levels. The positive expression rate of VEGF was significantly higher in MB tumor tissue, as compared with adjacent tissues (P<0.01). In addition, VEGF mRNA and protein expression levels in MB primary and secondary tumor tissues, and in the CSF of patients with metastatic MB, were significantly upregulated, as compared with tumor adjacent tissues and the CSF of patients with non-metastatic MB, respectively (P<0.01). miRNA-210 expression levels were significantly upregulated in MB tumor tissues, the CSF of patients with metastatic MB and in tumor tissues of metastatic MB (P<0.01). In the present study, the expression levels of VEGF and miRNA-210 were upregulated in patients with MB and metastatic MB; thus suggesting that miRNA-210 may promote the metastasis of MB primary tumors by regulating the expression of VEGF. PMID- 26668607 TI - Glycated albumin is an optimal biomarker for gestational diabetes mellitus. AB - Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance, which is a common complication that occurs in some women for the first time during the gestation period. However, the relationship between onset of GDM and factors including advanced age and a family history of diabetes remains to be determined. The study aimed to examine the clinical significance of the detection of glycated albumin (GA) in pregnant women with GDM. A total of 893 cases of pregnant women with GDM were included, with 661 healthy pregnant women serving as the normal controls. A conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and 95% confidence interval (95% CI). As the gestational weeks increased, the fasting blood glucose (FGP) concentration and GA-L value of the pregnant women in the normal control group gradually decreased whereas those of pregnant women with GDM greatly increased. The univariate analysis revealed that the impact factors on the occurrence of early-onset neonatal sepsis included, mother's age >35 years, complication of pregnancy hypertension, family history of hypertension, family history of diabetes, cesarean delivery, height, BMI, GA-L, and FGP. The multivariate logistic regression analysis revealed that the complication of pregnancy hypertension (OR=3.302; 95% CI, 1.705-6.394), family history of hypertension (OR=2.970; 95% CI, 1.520-5.801), GA-L (OR=1.556; 95% CI, 0.940 2.012) and FGP (OR=5.431; 95% CI, 4.097-7.198) were the main factors for pregnant women with GDM. In conclusion, pregnant women with GDM may be affected by various factors. Additionally, GA may be applied to reflect the recent blood glucose control on pregnant women with GDM. PMID- 26668608 TI - Topographic analysis of the mandibular symphysis in a normal occlusion population using cone-beam computed tomography. AB - At present, the relationship between the morphological characteristics of the sympheseal region and occlusion has not been well documented. The aim of the present study was to investigate the following, using cone-beam computed tomography (CBCT): Interforaminal distance, the anterior loop, labial bone thickness at the tooth apex, cortical bone thickness, and the basal bone height from the apex of the tooth to the base of the mandible. Three-dimensional CBCT was performed on 20 normal occlusion subjects (9 males and 11 females; mean age=21.9+/-3.0 years); the mean interforaminal distance was 53.1+/-3.6 mm, with 85% of the participants demonstrating a mental foramen located below the second premolars on both sides. The mean anterior loop was 1.9+/-0.8 mm, the mean horizontal distance value was 4.5+/-1.3 mm, and the mean cortical bone thickness value was 2.3+/-0.5 mm. An increasing tendency for cortical bone thickness was seen from the central incisor to the second premolar. The mean vertical distance value was 20.3+/-3.1 mm. Decreasing tendency of vertical distance was seen from the central incisor to the second premolar. Furthermore, the width (mental foramina of both sides and their anterior loops), height (teeth apices and the inferior border of the mandible), depth (cortical bone thickness of the symphysis), and safety margins for vital anatomical structures (anterior loop, tooth apex, and inferior border of mandible) should be taken into account prior to symphyseal block-bone harvesting. The results of the present study suggested that a pre-operative evaluation with CBCT may be useful for diagnosis and treatment planning, and for minimizing complications during block-bone graft. PMID- 26668609 TI - Association between colon diverticula and hemoglobin, triglyceride and uric acid levels. AB - Colon diverticula cause bleeding and acute diverticulitis. The present study analyzed laboratory test variables, aiming to predict the presence of diverticula. Patient records from between April 2011 and March 2014 were analyzed retrospectively (1,520 patients) and a one-way analysis of variance was performed to analyze the association between the presence of diverticula and each variable. A chi2 test was then used to assess the correlation between the prevalence of diverticula and the percentage of patients with uric acid (UA) levels >=5.1 mg/dl. A receiver operating characteristic (ROC) analysis was performed to determine the threshold values required to predict the presence of diverticula. Hemoglobin (Hb) levels were lower in patients with diverticula than in those without diverticula (P=0.0027), and compared with patients without diverticula, UA and triglyceride (TG) levels were higher in patients with diverticula (P=0.0066 and P=0.0136, respectively). The patients were divided into two groups, as follows: Patients with UA levels >=5.1 mg/dl (the median value) and those with UA levels <5.1 mg/dl. The prevalence of diverticula was significantly higher in patients with UA levels >=5.1 mg/dl than in those with UA levels <5.1 mg/dl (P=0.0004). ROC analysis demonstrated that the threshold values of Hb, TG and UA were 12,400, 146 and 5.1 mg/dl, respectively. The sensitivity of the Hb and UA levels at the threshold values was 76.5 and 71.0%, respectively. The prevalence of diverticula was associated with low Hb levels, and high TG and UA levels. PMID- 26668610 TI - Mechanisms of human amniotic epithelial cell transplantation in treating stage III pressure ulcer in a rat model. AB - The aim of the present study was to determine the function of human amniotic epithelial cell transplantation (hAECT) in promoting the healing of rats with stage III pressure ulcer (PU) and to initially investigate its possible mechanisms. A total of 96 Sprague Dawley rats were allocated at random into the model, hAECT, conventional treatment or control groups (n=24 per group). In each group, 6 rats were observed to determine the wound-healing rate. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-alpha in the wound tissue and serum were detected using reverse transcription-quantitative polymerase chain reaction analysis and enzyme linked immunosorbent assay. The transplantation of hAECs significantly increased the healing rate of the stage III PUs and was accompanied by the significant upregulation of VEGF mRNA and protein expression levels and the significant downregulation of TNF-alpha mRNA and protein expression. Immunofluorescence staining showed that, on day 7 of transplantation, hAECs remained alive inside the skin tissues. Therefore, hAECT through subcutaneous injection appears to significantly improve the wound-healing rate of stage III PUs in rats, and this effect may be associated with the upregulation of the proangiogenic factor VEGF and the downregulation of the inflammatory cytokine TNF-alpha. PMID- 26668611 TI - Comparative study of HPV16 integration in cervical lesions between ethnicities with high and low rates of infection with high-risk HPV and the correlation between integration rate and cervical neoplasia. AB - The etiology of a high incidence of cervical cancer in populations with a low human papillomavirus (HPV) infection rate is unclear. The current study aimed to investigate the role of HPV16 DNA integration in cervical lesions in women of Han and Uygur ethnicity and to explore the association between viral integration and a high cervical cancer morbidity with a low HPV infection rate. DNA was extracted from the biopsy specimens of cervical lesions of 379 patients of Uygur ethnicity and 464 patients of Han ethnicity, and multiple quantitative polymerase chain reaction (qPCR) assays were performed to determine the copy numbers of the HPV16 E2 and E6 genes. The copy number of the HPV16 DNA was evaluated according to the E2/E6 ratio. Among these cases, 122 Uygur and 121 Han specimens were found to be HPV16 positive. In the two populations, the percentage of cases with HPV16 integration (the sum of integrated-type infection only or a mixture of free-and integrated-type infection) increased with the grade of the cervical lesions (P<0.001). Within groups with the same cervical lesion grade, no significant differences in HPV16 integration were found between women of Uygur and Han ethnicity (rank sum test, P>0.05). No significant differences in the distribution of the HPV16 integration rate according to lesion grade were found in either population (P>0.05). When the two subpopulations were considered as one sample population, the integration rate significantly increased with lesion grade (P=0.02). These results indicate that the integration rate of HPV16 E2 may serve as a molecular biological marker for the development of cervical lesions. PMID- 26668612 TI - Clinical value of plasma B-type natriuretic peptide assay in pediatric pneumonia accompanied by heart failure. AB - Previous studies have shown that B-type natriuretic peptide (BNP) is useful in differentiating cardiac from pulmonary causes of dyspnea in adults. To date, international guidelines have recommended measurements of circulating BNP as a biomarker for diagnostic and prognostic purposes, as well as therapeutic monitoring, in adults with cardiac diseases, particularly those suffering from acute and chronic heart failure (HF). The aim of the present study was to investigate the differential diagnostic and therapeutic analysis of BNP levels assayed in pediatric pneumonia accompanied by HF. The clinical data of 80 patients with pneumonia, aged 1-3 years, were analyzed. The patients were divided into two groups: Simple pneumonia (46 cases) and pneumonia accompanied by HF (34 cases). All patients underwent two plasma BNP assays: The first one upon admission to the hospital and the second one prior to discharge. The plasma BNP levels of 20 healthy children were used as the negative control. Plasma BNP levels were measured using the Triage(r) BNP automated immunoassay systems and reagents. Statistical analysis showed that the plasma BNP levels of the patients upon admission were higher in the pneumonia accompanied by HF group compared with those in the simple pneumonia group (750+/-120 vs. 135+/-50 pg/ml; P<0.05). In addition, in the pneumonia accompanied by HF group, the plasma BNP levels of the patients were higher upon admission to the hospital than they were prior to discharge (750+/-120 vs. 115+/-45 pg/ml; P<0.05); therefore, plasma BNP may comprise a sensitive diagnostic and therapeutic evaluative marker for pediatric patients with pneumonia accompanied by HF. This finding could prove invaluable in the clinical diagnosis and treatment of the disease. PMID- 26668613 TI - Comparative efficacy and cost effectiveness of splenectomy and thrombopoietin prior to peginterferon and ribavirin therapy with compensatory cirrhosis associated with hepatitis C and thrombocytopenia. AB - The aim of the present study was to evaluate and compare the treatment efficacy and cost of two therapies, splenectomy and thrombopoietin, in order to optimize the treatment plans for patients with HCV-associated cirrhosis. A prospective randomized controlled trial was conducted on 69 patients with a platelet count <60,000/mm3 that were enrolled between 2009 and 2013, including 38 cases as the research group and 31 cases as the observed group. The study included two stages: A 4-week initial treatment and a 48-week antiviral treatment, during which a number of parameters were evaluated, including platelet count, liver stiffness measure, albumin, total bilirubin, alanine aminotranferase and treatment cost effectiveness. Of the 38 patients, 21 underwent a splenectomy and their platelet counts increased to 60,000/mm3 after the 4-week initial treatment. The patients then started a 48-week P-R antiviral treatment, and 18 cases completed the treatment. In addition, 17/38 patients received thrombopoietin as a drug therapy. The platelet counts in 15 cases increased to >60,000/mm3 and the patients received antiviral treatment, among which 9 cases completed the second treatment stage. The expense of the splenectomy group treatment was higher compared with that received by the thrombopoietin group. The results of the present study indicated that splenectomy was more effective at increasing platelet count. More splenectomy patients completed the full course of antiviral treatment and presented a sustained virologic response, compared with the thrombopoietin group. Therefore, splenectomy may be more expensive compared with thrombopoietin; however, the improved efficacy suggests that on balance it is the preferable treatment option. PMID- 26668615 TI - Bladder exstrophy-epispadias complex with adenocarcinoma in an adult patient: A case report. AB - The present case report presents the case of exstrophy-epispadias complex (EEC) with the widest separation of the symphysis pubis to date. A 33-year-old male was referred to hospital with previously unreconstructed EEC malformation. The diagnosis established was of EEC with separation of the symphysis pubis and left inguinal hernia with adenocarcinoma of the bladder. The patient underwent radical cystectomy plus an ileal conduit and an expanded local lymphadenectomy. Osteotomy was not performed, and instead the defect of the pelvis and abdominal wall was repaired using meshes and a lower abdominal island skin flap. At 1 year after surgery the patient recovered well, with no indications of mesh distortion or major complications. PMID- 26668614 TI - Use of a correlation analysis model in the optimization of intensity-modulated radiotherapy of prostate cancer. AB - The aim of the present study was to develop a statistical model-based method for the optimization of intensity-modulated radiotherapy (IMRT). A prostate cancer IMRT plan was redesigned while retaining the same beam orientation and prescribed dose as the regular plan. A series of dosimetric parameters were generated, and a 4-step protocol was performed to analyze the data: i) The tumor control probability of the target was ensured by setting a number of strict constraint parameters so that much of the target was covered by the 95% isodose line; ii) the parameters for optimization [weight ratio, equivalent characteristic parameter a and maximum equivalent uniform dose of the organ at risk (OAR)] were adjusted; iii) the overall optimization space (OOS) was determined via analysis of the dose-parameter tables based on the correlation factor (CF) and optimization efficiency factor analysis; iv) the OOS in the Pinnacle V7.6 treatment planning system with IMRT function was transposed. A selected optimization phenomenon existed when different optimization methods were used to optimize dose distribution to the targets and OARs, which demonstrates a wide variation in the CFs between the percentage of planning target volume receiving 95% of the prescribed dose and the maximum dose of the bladder, rectum and femur. The OOS used to optimize the randomly selected plan exhibited relatively high efficiency, with benefits for the optimization of IMRT plans. For patients with prostate cancer who require complex IMRT plan optimization, the obtained OOS from the two core analysis techniques is likely to have relatively high efficiency in achieving an optimized plan. These results suggest that the correlation analysis model is a novel method for the optimization of IMRT for prostate cancer. PMID- 26668616 TI - Pharmacological preconditioning and postconditioning with nicorandil attenuates ischemia/reperfusion-induced myocardial necrosis and apoptosis in hypercholesterolemic rats. AB - Pharmacological preconditioning and postconditioning may reduce myocardial necrosis and apoptosis during ischemia/reperfusion (I/R), however, hypercholesterolemia interferes with the associated cardioprotective mechanisms. The present study investigated whether pharmacological preconditioning and postconditioning with nicorandil could attenuate myocardial necrosis and apoptosis induced by I/R in hypercholesterolemic rats, and explored the possible mechanisms involved. Male Wistar rats (n=160) were fed normal (normocholesterolemic group, n=10) or high-cholesterol (hypercholesterolemic group, n=150) diets for 8 weeks. Hearts harvested from the normal and hypercholesterolemic rats were subsequently placed on modified Langendorff perfusion apparatus and 30-min global ischemia was performed, followed by 120-min reperfusion. Nicorandil (1, 3, 10, 30, 100 umol/l), and mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channel blocker 5-hydroxydecanoic acid sodium salt (5-HD) (100 umol/l) or soluble guanylyl cyclase (sGC) blocker 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 umol/l) were perfused for 10 min, prior to ischemia or at the onset of reperfusion. The myocardial infarct size was determined by triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. In order to investigate the potential mechanisms, the expression levels of caspase-3, B-cell lymphoma-2 (Bcl-2) proteins and Bcl-2 associated X protein (Bax) were measured using western blot analysis. The present study demonstrated that, in hypercholesterolemic rats, pharmacological preconditioning and postconditioning with nicorandil decreased I/R-induced myocardial necrosis and apoptosis in a concentration-dependent manner. The optimal preconditioning and postconditioning concentration of nicorandil determined to have anti-infarct and anti-apoptosis effects was 30 umol/l, which significantly (P<0.05) reduced the infarct size to 14.88+/-3.25% and 15.96+/ 3.29%, and attenuated the percentage of cardiomyocyte apoptosis to 25.20+/-3.93% and 26.18+/-4.82%, respectively, compared with the I/R group. However, the cardioprotective effects of nicorandil were partially suppressed by cotreatment with 5-HD or ODQ. Western blot analysis demonstrated that pharmacological preconditioning and postconditioning with nicorandil significantly downregulated caspase-3 and Bax expression, and upregulated Bcl-2 expression compared with the I/R group (P<0.05). The results of the present study suggest that pharmacological preconditioning and postconditioning with nicorandil may protect hypercholesterolemic hearts against I/R-induced necrosis and apoptosis; and the cardioprotective effects of nicorandil may be due to the dual pharmacological mechanisms of opening the mitoKATP channels and a nitric oxide/sGC-dependent mechanism, and regulation of the expression of caspase-3, Bax and Bcl-2. PMID- 26668618 TI - A rare case of juvenile localised scleroderma with intra-oral and dental involvement. AB - Juvenile localised scleroderma is a rare childhood disorder of the immune system and connective tissue with unknown etiology. There are different types of localised scleroderma, including linear scleroderma (where the lesion appears as a line or streak) and plaque or circumscribed morphea (where the lesion appears as a roundish lesion). The present report describes the case of a 10-year-old girl, who presented with a history of linear scleroderma with nose, oral and dental involvement, and outlines the diagnosis of the case based on the clinical presentation, pathology, X-ray and cone beam computed tomography images. The treatment strategy that was selected for the patient is additionally discussed. PMID- 26668619 TI - Cell sheet-engineered bones used for the reconstruction of mandibular defects in an animal model. AB - The aim of the present study was to investigate the generation of cell sheet engineered bones used for the reconstruction of mandibular defects. Bone marrow stem cells (BMSCs) were cultured and induced to generate osteoblasts. Poly(lactic co-glycolic acid) (PLGA) scaffolds were wrapped with or without cell sheets and then implanted into dogs with mandibular defects in the right side (experimental group) or the left side (control group), respectively. Subsequently, X-ray analyses, and hematoxylin and eosin staining were performed at various time points (at 4, 8, 12 or 16 weeks post-implantation; n=4 at each time point). The osteogenesis in the experimental group was significantly improved compared with that in the control group. At 16 weeks after implantation, numerous Haversian systems and a few lamellar bones were observed at the periphery. In the control group, the engineered bone (without BMSC sheets) presented fewer Haversian systems and no lamellar bones. The optical density of the fresh bone in the experimental group was significantly higher compared with that in the control group (P<0.05). In conclusion, tissue-engineered bone with the structure of lamellar bones can be generated using BMSC sheets and implantation of these bones had an improved effects compared with the control group. Cell sheet transplantation was found to enhance bone formation at the reconstruction site of the mandibular defects. PMID- 26668617 TI - Naringenin attenuates pressure overload-induced cardiac hypertrophy. AB - Cardiac hypertrophy is characterized by abnormal enlargement of cardiomyocytes and disproportionate accumulation of extracellular interstitial fibrosis, which are major predictors of the development of coronary artery disease and heart failure. Naringenin is a bitter principle component of grapefruit that has numerous pharmacological effects, including anti-inflammatory, hypolipidemic, antithrombotic and antiatherogenic properties. In order to investigate whether naringenin is able to exert a protective effect against cardiac hypertrophy induced by pressure overload, aortic banding (AB) was performed to induce cardiac hypertrophy in mice, and naringenin was administered for 7 weeks. A total of 60 mice were allocated into four groups: Sham + vehicle, AB + vehicle, sham + naringenin and AB + naringenin. Naringenin treatment attenuated cardiac dysfunction, as indicated by the results of echocardiography and catheter-based measurements at 8 weeks post-surgery. The extent of cardiac hypertrophy was assessed by the heart weight/body weight, heart weight/tibial length and lung weight/body weight ratios, in addition to the cardiomyocyte cross-sectional area and the mRNA expression levels of hypertrophic maker, all of which were mitigated by naringenin administration. Naringenin also inhibited the expression of transforming growth factor-beta1, connective tissue growth factor, collagen Ialpha and collagen IIIalpha, and attenuated interstitial fibrosis. In addition, naringenin downregulated the activation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In conclusion, naringenin attenuated cardiac hypertrophy and interstitial fibrosis, in addition to improving left ventricular function in pressure-overloaded mice. The cardioprotective effect exerted by naringenin may be associated with the inhibition of PI3K/Akt, ERK and JNK signaling pathways. PMID- 26668620 TI - Adult cervicomedullary pilocytic astrocytoma: A case report. AB - Pilocytic astrocytoma (PA) is a rare glioma, which generally occurs in children and young adults. In adult patients, the majority of PA tumors are supratentorial. Due to the low morbidity rate of the disease in adults, PA is frequently misdiagnosed and mistreated. In the present study, this rare disease was successfully treated. The study reported the case of a 48-year-old patient with a cervicomedullary occupying lesion, who complained of numbness and pain of the right limbs that persisted for >10 years, with aggravation for 1 month. A magnetic resonance imaging scan showed a sharp cervicomedullary mass extending from the lower medulla to the cervical vertebra C3 level. Intraoperatively, the medulla and upper cervical cord were found to be well-stacked. Immediately after ingression into the spinal cord along the dorsal median sulcus, the tumor mass was detected and had a gray fish-like appearance, moderate blood supply and clear boundary. After intratumoral decompression, total excision was achieved. Postoperative pathological examination confirmed that the tumor was a PA. Following discharge, the patient did not suffer from any symptoms of the lower cranial nerves and was able to walk with limited assistance. PMID- 26668621 TI - Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation. AB - Chronic administration of immunosuppressants has been associated with long-term consequences, including a higher risk of neoplasm development. The processes regulating telomere function exert a major influence on human cancer biology. The present study aimed to assess the effect of immunosuppressive therapy on the expression of genes associated with telomere maintenance and protection in patients following renal transplantation. A total of 51 patients that had undergone kidney transplantation and 54 healthy controls were enrolled in the study. The 51 transplant patients received a three-drug immunosuppressive regimen consisting of cyclosporine A, prednisone and mycophenolate mofetil. In stage 1 of the study, the expression profiles of 123 transcripts, which represented 70 genes, were assessed in peripheral mononuclear blood cells using an oligonucleotide microarray technique in 8 transplant recipients and 4 healthy control subjects. Among the analyzed transcripts, the expression levels of 4 differed significantly between the studied groups; however, only the ACD (adrenocortical dysplasia homolog) gene, encoding the telomere-binding protein POT1-interacting protein 1 (TPP1), was sufficiently specific for telomere homeostasis. The expression of ACD was downregulated in transplant recipients (fold change, 2.11; P=0.006). In stage 2 of the study, reverse transcription quantitative polymerase chain reaction analysis of ACD, DKC1 and hTERT mRNA was conducted for all transplant patients and control subjects. The results confirmed the downregulation of the ACD gene in patients that had received immunosuppressive therapy (P=0.002). The results of the present study indicate that the downregulation of ACD gene transcription, and thus TPP1 protein expression, may enhance the capacity for cell immortalization, despite normal levels of other key telomere maintenance factors, in patients undergoing immunosuppressive therapy. Furthermore, the results indicate that TPP1 has potential for use as an early clinical marker and/or therapeutic target for cancer in patients following organ transplantation. PMID- 26668622 TI - Epigallocatechin-3-gallate-induced inhibition of interleukin-6 release and adjustment of the regulatory T/T helper 17 cell balance in the treatment of colitis in mice. AB - Epigallocatechin-3-gallate (EGCG) has a promising therapeutic effect for ulcerative colitis (UC), but the treatment mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism of EGCG in the treatment of UC. Experimental colitis mouse models were prepared. The mice were randomly divided into four groups: Normal control, model (MD), 50 mg/kg/day EGCG treatment and 100 mg/kg/day EGCG treatment. The daily disease activity index (DAI) of the mice was recorded, changes in the organizational structure of the colon were observed and the spleen index (SI) was measured. In addition, levels of interleukin (IL)-6, IL-10, IL-17 and transforming growth factor (TGF)-beta1 in the plasma and hypoxia-inducible factor (HIF)-1alpha and signal transducer and activator of transcription (STAT) 3 protein expression in colon tissues were evaluated. Compared with the MD group, the mice in the two EGCG treatment groups exhibited decreased DAIs and SIs and an attenuation in the colonic tissue erosion. EGCG could reduce the release of IL-6 and IL-17 and regulate the mouse splenic regulatory T-cell (Treg)/T helper 17 cell (Th17) ratio, while increasing the plasma levels of IL-10 and TGF-beta1 and decreasing the HIF-1alpha and STAT3 protein expression in the colon. The experiments confirmed that EGCG treated mice with experimental colitis by inhibiting the release of IL-6 and regulating the body Treg/Th17 balance. PMID- 26668623 TI - Solitaire AB stent-assisted coiling embolization for the treatment of ruptured very small intracranial aneurysms. AB - Recent advances in neuroradiological techniques have increasingly improved the diagnosis rate for very small aneurysms, particularly with the widespread use of three-dimensional cerebral angiography. However, the treatment of very small aneurysms remains a considerable challenge for neurosurgeons. Endovascular coiling has emerged as a potential treatment option for intracranial aneurysms. The aim of the present study was to evaluate the safety and efficacy of Solitaire AB stent-assisted coiling embolization for the treatment of ruptured very small intracranial aneurysms. This retrospective study included nine consecutive patients with ruptured very small intracranial aneurysms (<=3 mm) that underwent Solitaire AB stent-assisted coiling embolization. The aneurysms were located in the ophthalmic branch of the internal carotid artery (n=2), the posterior communicating branch of the internal carotid artery (n=4), the top of the basilar artery (n=1) and the middle cerebral artery (n=2). Solitaire AB stents were successfully implanted in all nine patients. Of the nice individuals, six patients exhibited complete occlusion at Raymond grade I and three patients exhibited occlusion at Raymond grade II. No aneurysm rupture was observed during the surgery. During the follow-up period of 8-13 months, no intracranial hemorrhage occurred. A total of seven patients underwent follow-up digital subtraction angiography at 5-10 months post-intervention. No recurrence of the aneurysms and no stenosis or occlusion of the parent arteries was observed. Therefore, Solitaire AB stent-assisted coil embolization was demonstrated to be a safe and effective treatment for ruptured very small intracranial aneurysms. The long-term efficacy of this technique may be improved by increasing the packing density around the aneurysmal neck and improving the hemodynamics. PMID- 26668624 TI - microRNA and gene networks in human laryngeal cancer. AB - Genes and microRNAs (miRNAs) are considered to be key biological factors in human carcinogenesis. To date, considerable data have been obtained regarding genes and miRNAs in cancer; however, the regulatory mechanisms associated with the genes and miRNAs in cancer have yet to be fully elucidated. The aim of the present study was to use the key genes and miRNAs associated with laryngeal cancer (LC) to construct three regulatory networks (differentially expressed, LC-related and global). A network topology of the development of LC, involving 10 differentially expressed miRNAs and 55 differentially expressed genes, was obtained. These genes exhibited multiple identities, including target genes of miRNA, transcription factors (TFs) and host genes. The key regulatory interactions were determined by comparing the similarities and differences among the three networks. The nodes and pathways in LC, as well as the association between each pair of factors within the networks, such as TFs and miRNA, miRNA and target genes and miRNA and its host gene, were discussed. The mechanisms of LC involved certain key pathways featuring self-adaptation regulation and nodes without direct predecessors or successors. The findings of the present study have further elucidated the pathogenesis of LC and are likely to be beneficial for future research into LC. PMID- 26668625 TI - Peritoneal dialysis treatment for severe lupus nephritis patients complicated with essential organ dysfunction. AB - The aim of the present study was to evaluate the clinical efficacy of peritoneal dialysis (PD) in patients with severe lupus nephritis (LN) complicated with organ dysfunction. In total, 13 severe LN patients complicated with multiple-organ dysfunction, who underwent PD treatment between November 2003 and September 2010, were enrolled in the study. Six patients received methylprednisolone pulse therapy due to lupus activity and progressive renal failure. These patients were complicated with severe edema, cardiac insufficiency and severe hypoalbuminemia. PD was applied to the patients, followed by the administration of immunosuppressants. Patients were followed-up to review the parameters of renal function, the immunological indexes and the systemic lupus erythematosus disease activity index. The results indicated that the general state of health was markedly improved following PD treatment, with edema abatement and improvement of heart function and physical strength. Serum creatinine levels significantly decreased from 6.3+/-1.6 to 2.6+/-1.0 mg/dl. A total of 10 cases ceased PD treatment during the follow-up, while three cases continued PD to the end of the follow-up period. The levels of albumin and hemoglobin exhibited a marked increase from 29.7+/-5.7 to 35.2+/-5.5 g/l and 8.7+/-1.8 to 9.8+/-1.8 g/l, respectively. There was one case of peritonitis, one case of peritoneal leakage and two cases of pneumonia. Therefore, PD may be a successful treatment method for severe LN patients complicated with essential organ dysfunction. PD not only improved the symptoms of edema and heart failure, but also played an important role in preserving residual renal function and improving the nutritional state of the patients. Thus, PD can be considered as a treatment option for patients with severe LN associated with acute kidney injury, however, selecting a suitable immunosuppressant during PD treatment is essential. PMID- 26668626 TI - Eriodictyol, a plant flavonoid, attenuates LPS-induced acute lung injury through its antioxidative and anti-inflammatory activity. AB - Acute lung injury (ALI) is characterized by excessive inflammatory responses and oxidative injury in the lung tissue. It has been suggested that anti-inflammatory or antioxidative agents could have therapeutic effects in ALI, and eriodictyol has been reported to exhibit antioxidative and anti-inflammatory activity in vitro. The aim of the present study was to investigate the effect of eriodictyol on lipopolysaccharide (LPS)-induced ALI in a mouse model. The mice were divided into four groups: Phosphate-buffered saline-treated healthy control, LPS-induced ALI, vehicle-treated ALI (LPS + vehicle) and eriodictyol-treated ALI (LPS + eriodictyol). Eriodictyol (30 mg/kg) was administered orally once, 2 days before the induction of ALI. The data showed that eriodictyol pretreatment attenuated LPS-induced ALI through its antioxidative and anti-inflammatory activity. Furthermore, the eriodictyol pretreatment activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the ALI mouse model, which attenuated the oxidative injury and inhibited the inflammatory cytokine expression in macrophages. In combination, the results of the present study demonstrated that eriodictyol could alleviate the LPS-induced lung injury in mice by regulating the Nrf2 pathway and inhibiting the expression of inflammatory cytokines in macrophages, suggesting that eriodictyol could be used as a potential drug for the treatment of LPS-induced lung injury. PMID- 26668627 TI - Caspase-8 polymorphisms and risk of oral squamous cell carcinoma. AB - Caspase-8 (CASP8) is a key controller of apoptosis, and its deregulation is crucially involved in carcinogenesis. The aim of the present study was to evaluate the function of CASP8 polymorphisms in oral squamous carcinoma (OSCC) by evaluating the risk associated with three single-nucleotide polymorphisms (SNPs) in a case-control study in a Han Chinese patient population. A total of 505 individuals with clinically diagnosed OSCC and 507 healthy controls were tested for the three SNPs rs3834129, rs13016963 and rs1045485, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. After adjusting for other confounders, the genotype frequencies of CASP8 -652 6N ins/del promoter polymorphism (rs3834129) were found to be lower in patients with OSCC compared with normal subjects. No significant difference was detected in the genotype frequencies of rs13016963 between the patients and control subjects. However, the AA genotype frequency of rs1306963 was associated with OSCC as a risk factor among non-smokers and non-drinkers. For CASP8, rs1045485 was not present in any of the patients with OSCC or control subjects. These results suggest that the del allele of rs3834129 may play a protective role in the tumorigenesis of OSCC and may be useful as a genetic susceptibility marker for OSCC in the population studied. PMID- 26668628 TI - Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. AB - Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to investigate whether hydrogen-rich saline treatment could attenuate ovarian damage induced by cisplatin. A total of 240 adult, virgin, female Sprague Dawley rats, weighing 180-220 g, were randomly divided into four groups (n=60 per group): Control (Con), control + hydrogen-rich saline (Con + H2), cisplatin-induced ovarian injury (OI) and cisplatin-induced ovarian injury + hydrogen-rich saline (OI + H2). Cisplatin was diluted in saline immediately before use. In the OI and OI + H2 groups, the rats were administered a dose of cisplatin on the 1st and 7th days. The rats in the Con + H2 and OI + H2 groups were intraperitoneally injected with hydrogen-rich saline (10ml/kg body weight) once a day over a 2-week period. On the 14th, 28th and 42nd days (T1, T2 and T3) after the cisplatin injection, femoral vein blood was collected. At the end of the experiment, ovarian homogenates were prepared, and the samples were used for estrogen (E2), follicle-stimulating hormone (FSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) examination. In addition, rats (n=10 per group) were sacrificed for bilateral ovary removal; one was fixed in formalin for follicle-counting analysis, while the other was used for nuclear factor erythroid 2-related factor 2 (Nrf2) detection by western blotting. Hydrogen-rich saline attenuated the FSH release, elevated the level of E2, improved the development of follicles, and reduced the damage to the ovarian cortex at T1, T2 and T3 in the OI + H2 rats. Cisplatin induced oxidative stress by increasing the levels of oxidation products and attenuating the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment. Furthermore, hydrogen-rich saline regulated the Nrf2 protein expression in rats with ovarian damage. In conclusion, hydrogen-rich saline exerts a protective effect against cisplatin induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2. PMID- 26668629 TI - Construction and identification of an RNA interference lentiviral vector targeting the mouse TNF-alpha gene. AB - The aim of this study was to construct RNA interference (RNAi) lentiviral vector particles targeting the mouse tumor necrosis factor-alpha (TNF-alpha) gene. Three types of small interfering RNA (siRNA) targeting the mouse TNF-alpha gene were designed, synthesized and transfected into RAW264.7 cells. Screening was performed to identify the siRNA sequence exhibiting the highest inhibition efficiency; based on this, recombinant lentiviral plasmids were constructed and co-transfected into 293T cells with packaging plasmids for the production of lentiviral particles. The screening results showed that the TNF-alpha mRNA expression levels of the three siRNA groups were significantly lower than those of the negative control group, with the highest inhibition rate in the siRNA2 group (83.09%). Similarly, the expression levels of TNF-alpha protein in the three siRNA groups were significantly lower than those of the negative control group, and the highest inhibition rate was found in the siRNA2 group (51.16%). The mRNA expression of interleukin (IL)-1beta and IL-6 showed no significant difference among the siRNA groups and the negative control. The recombinant lentiviral shuttle plasmid was constructed, and electrophoresis revealed the polymerase chain reaction product to be 343 bp, while that of the empty vector was 306 bp; DNA sequencing showed partial insertion. The virus titer was calculated to be 2*106 TU/ul. In conclusion, RNAi lentiviral vector particles targeting the mouse TNF-alpha gene were successfully obtained in the present study. This method may be used to produce lentiviral vector for the in vivo study of RNAi gene therapy targeting TNF-alpha. PMID- 26668630 TI - Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A. AB - CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40 degrees C or within a broad pH range (pH 5.0-7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics. PMID- 26668631 TI - Long-term remission induced by low-dose rituximab for relapsed and refractory thrombotic thrombocytopenic purpura: A report of two cases. AB - Thrombotic thrombocytopenic purpura (TTP) is acquired in the majority of cases. Traditional therapy consists of plasma exchange (PEX), as well as the administration of certain immunosuppressive agents including steroids. A standard dose of rituximab (RTX) at 375 mg/m2 weekly for 4 consecutive weeks was recently demonstrated to have significant activity in patients with acquired TTP. To date, clinicians have limited experience using low-dose RTX. In the present study, 2 patients were treated with low-dose RTX at 100 mg weekly for 4 consecutive weeks as a salvage therapy following failure to respond to PEX and other immunosuppressive agents. Prior to RTX therapy, the patients had severely deficient ADAMTS13 activity and detectable anti-ADAMTS13 inhibitors. The patients achieved complete remission and presented long-term stabilization during follow up. Repeated detection during follow-up demonstrated that the patients had 100% ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies. Although further investigation in a prospective clinical trial is required, the use of low-dose RTX seems to be as effective as a standard dose for patients with relapsing or refractory acquired TTP. PMID- 26668632 TI - Clinical and histological predictive risk factors of atrial fibrillation in patients undergoing open-heart surgery. AB - Postoperative atrial fibrillation (POAF) is a common complication subsequent to cardiac surgery. Various risk factors have been reported for the development of this complication; however, their precise role in POAF is unknown. In the present study, we attempted to identify clinical factors and histopathological changes in atrial tissue that may predict the development of POAF. Atrial tissue was sampled from 103 patients in sinus rhythm that had undergone open-heart surgery, including elective coronary artery bypass grafting (79.61%) and heart valve surgery (20.38%). Atrial surgical biopsies were obtained from the right atrial appendage at the site of cannulation, prior to cardiopulmonary bypass. Tissues were processed routinely for light microscopy, then stained with hematoxylin and eosin and sirius red. Microscopical exams were used to observe the atrial lesions and morphometry was conducted for quantification. In total, 37 patients (35.92%) developed POAF and atrial lesions were identified in the majority of patients in the normal postoperative sinus rhythm and POAF groups, but were most common in the POAF patients. The most common risk factors involved in developing POAF were found to be: Age of >60 years, male gender, ejection fraction of <50% and increased pulmonary hypertension. Furthermore, interstitial fibrosis and myocytolysis were the most common injuries identified. Abnormalities in atrial surgical biopsies may indicate the susceptibility of a patient to developing POAF. The present results suggest that the pre-existent alterations in the structure of the right atrium may be a major determinant in the development of POAF. PMID- 26668633 TI - Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers. AB - Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell killing effect of the nanoparticles may be attributable to their sustained drug release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers. PMID- 26668634 TI - Effect of changes in sympathovagal balance on the accuracy of heart rate variability obtained from photoplethysmography. AB - Heart rate variability (HRV) obtained using photoplethysmography (PPG), which is also known as pulse rate variability (PRV), has already been used in clinical practice. However, it is uncertain whether PRV reflects changes in autonomic nervous function accurately. The aim of the present study was to evaluate quantitatively the effect of alterations in the sympathovagal balance on the agreement between PRV and HRV from electrocardiographs (ECG). Healthy subjects (male, 26; female, 7; age, 22-25 years old) participated in the present study. Paced respiration with 15 breathes/min and breath holding (apnea) were performed to alter the autonomic nervous states of patients. The changes in the low-to-high frequency power ratio (LF/HF) of HRV indicated that there was a sympathovagal balance shift toward vagal predominance during paced respiration, but toward sympathetic predominance during apnea. The results demonstrated that, during paced respiration, all indices had an acceptable agreement [Bland-Altman ratio (BAr)<0.2] between PRV and HRV, with the exception of LF/HF that had an insufficient agreement (BAr=0.25). All indices had very strong correlations [Pearson's correlation coefficients (CC)>0.99] and PRV had a minor but highly significant (P<0.001) increase for the majority of the variability indices, when compared with HRV. During apnea, the discrepancy of the short-term variability indices between PRV and HRV became sizeable with a BAr>0.3 and a minimum CC of 0.96. In conclusion, a decrease of LF/HF caused a marginal inaccuracy of PRV in the indication of sympathovagal balance, while sympathetic activation increased differences in short-term variability between PRV and HRV. PMID- 26668635 TI - BET protein inhibition mitigates acute myocardial infarction damage in rats via the TLR4/TRAF6/NF-kappaB pathway. AB - Acute myocardial infarction (AMI) is among the most serious cardiovascular diseases and is a leading cause of mortality in developed countries. Previous studies have indicated the central role played by the bromodomain (BRD) proteins, which belong to the BRD and extra-terminal (BET) family, in gene control during heart failure pathogenesis. In addition, BET inhibition has been shown to suppress cardiomyocyte hypertrophy. However, the role of BET proteins in myocardial infarction remains unclear. The present study aimed to investigate whether BETs inhibition mitigates AMI, and explore the molecular mechanism underlying this effect. A rat model of acute myocardial infarction was established, and rats were divided into the sham, AMI and AMI + JQ1 groups. JQ1, a well-known selective BRD inhibitor, was used to suppress BET domain family activity. The mRNA and protein expression levels of BRD2, BRD3 and BRD4 were evaluated using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of markers of cardiac damage were determined using commercial kits. The results indicated that BRD2 and BRD4 mRNA and protein expression levels were significantly increased in the AMI group compared with those in the sham group. In addition, BET inhibition decreased AMI damage in vivo by reversing cardiac function injury, decreasing serum lactate dehydrogenase and creatine kinase-MB isozyme activity, in addition to decreasing the expression levels of high-sensitivity C-reactive protein and interleukin-6. Furthermore, the results suggested that Toll-like receptor 4 (TLR4) signaling was activated by the increased expression of TLR4, TNF receptor-associated factor 6 (TRAF6) and nuclear factor (NF)-kappaB during AMI. However, JQ1 treatment suppressed TLR4 signaling activation. In conclusion, the present results demonstrated that the inhibition of BET family proteins suppresses AMI, and that this effect was partially mediated by the inhibition of TLR4/TRAF6/NF-kappaB signaling. PMID- 26668637 TI - Low-molecular-weight heparin and intermittent pneumatic compression for thromboprophylaxis in critical patients. AB - The efficacy and safety of physiotherapeutic prophylaxis for venous thromboembolism in critically ill patients with heparin contraindication remains unclear. In the present study it was hypothesized that physiotherapy prophylaxis with intermittent pneumatic compression (IPC) would be safe and effective for patients unable to receive low-molecular-weight heparin (LMWH). In addition, this study investigated whether a combined therapy of IPC with LMWH would be more effective for the prophylaxis of deep vein thrombosis (DVT) in critical patients. A total of 500 patients were divided into four groups according to the prophylaxis of DVT. The IPC group consisted of 95 patients with heparin contraindication that received IPC treatment; the LMWH group consisted of 185 patients that received an LMWH injection; the LMWH + IPC group consisted of 75 patients that received IPC treatment and LMWH injection; and the control group consisted of 145 patients that received no IPC treatment or injection of LMWH. Each patient was evaluated clinically for development of DVT and the diagnosis was confirmed by Doppler study. Venous thromboembolism was a common complication among the trauma patients with severe injuries. Patients responded positively to the treatment used in the intervention groups. Patients exhibited an improved response to LMWH + ICP compared with IPC or LMWH alone, while no significant difference was detected between the IPC and LMWH groups. These results were applicable to patients that had a Wells score of >=3; however, no significant differences in DVT incidence were observed among the patients who had a Wells score of <3. In this observational study, LMWH + ICP appeared to be more effective than either treatment alone in treating critically ill trauma patients with severe injuries that are at high risk for VTE and bleeding simultaneously. PMID- 26668636 TI - Ultrastructural identification of telocytes in the muscularis of chicken ileum. AB - Telocytes (TCs) are a specialized type of interstitial cells, characterized by a small cell body and long, thin processes, that have recently been identified in various cavitary and non-cavitary organs of humans and laboratory mammals. Chickens present significant economical and scientific notability; however, ultrastructural identification of TCs remains unclear in birds. The aim of the present study was to describe electron microscopic evidence for the presence of TCs in the chicken gut. The ileum of healthy adult broiler chickens (n=10) was studied by transmission electron microscopy. TCs are characterized by several, long (tens to hundreds of um) prolongations called telopodes (Tps). Tps, which are below the resolving power of light microscopy, display podomeres (thin segments of <=0.2 um) and podoms (dilations accommodating caveolae, mitochondria and endoplasmic reticulum). TCs were observed in every field, but were predominantly located in the myenteric plexus and the lamina propria. Tps frequently establish close spatial relationships with immune cells, blood vessels and nerve endings. On the basis of their distribution and morphology, it was hypothesized that the different locations of TCs may be associated with different roles. PMID- 26668638 TI - Epidemiology and clinical features of segmental/lobar pattern Mycoplasma pneumoniae pneumonia: A ten-year retrospective clinical study. AB - Mycoplasma pneumoniae plays an important role in community-acquired pneumonia. However, epidemiological and clinical studies on the segmental/lobar pattern (S/L) radiographic-pathologic subtype of pediatric Mycoplasma pneumoniae pneumonia (MPP) are rare. The current study retrospectively analyzed the epidemiological and clinical characteristics of pediatric MPP patients. A total of 1,933 children with MPP received treatment at a single hospital between 2000 and 2009, of which 684 (35.4%) were diagnosed with S/L-MPP. The annual incidence of S/L-MPP in children with MPP increased throughout the duration of this study (from 6.4 to 59.6%, P<0.001), which was particularly evident after 2003. S/L-MPP was predominantly found in pre-school-aged children (4-6 years old; 56.6%). Compared with non-S/L-MPP, S/L-MPP was more closely associated with severe manifestations, including higher rates of fever (90.2 vs. 83.3%), pleural effusion (3.9 vs. 1.3%), extrapulmonary manifestations (26.2 vs. 21.2%), abnormal white blood cell counts (65.5 vs. 55.2%), abnormal C-reactive protein levels (30.9 vs. 23.7%) and bacterial co-infection (32.0 vs. 24.9%), as well as longer durations of fever (4.13+/-4.28 vs. 3.02+/-2.22 days) and hospitalization (12.70+/-4.54 vs. 9.22+/-5.12 days). Older S/L-MPP patients showed higher rates and longer durations of fever and cough; however, they also displayed a lower rate of extrapulmonary manifestations when compared with younger patients. In conclusion, the annual incidence of S/L-MPP has increased in recent years. Pre school-aged children (4-6 years) with MPP are more likely to display a segmental/lobar pattern, which is associated with more severe clinical manifestations than other MPP infection patterns. PMID- 26668639 TI - Effect of low-dose diuretics on the level of serum cystatin C and prognosis in patients with asymptomatic chronic heart failure. AB - The aim of the present study was to investigate the effect of low-dose diuretics on the serum cystatin C (CysC) and serum creatinine (Scr) levels, and on the prognosis in patients with asymptomatic chronic heart failure (HF). A total of 66 asymptomatic chronic HF patients were divided into the observation and control groups (n=33 in each group). Patients in the control group were treated with a routine treatment, while the patients in the observation group were treated with the diuretic hydrochlorothiazide along with the same routine treatment as the control group. The left ventricular ejection fraction (LVEF), serum CysC levels, Scr levels, heart function, prognosis, adverse reactions and complications of the patients in the two groups were compared prior to and following treatment. The LVEF increased in the two groups following treatment, while the levels of serum CysC and Scr decreased. The LVEF in the observation group increased following treatment for 1, 3 and 6 months compared with the LVEF values in the control group. In addition, the levels of serum CysC and Scr in the observation group were found to be lower compared with those in the control group (P<0.05). The incidence of adverse prognosis following treatment for 6 months in the observation group was lower compared with that in the control group (P<0.05). The proportion of HF patients with New York Heart Association (NYHA) class I and II increased following treatment for 6 months in the two groups (P<0.05). However, in the observation group, a higher number of patients exhibited class I and II disease after treatment for 6 months compared with the number in the control group (P<0.05). Furthermore, no statistically significant difference was observed between adverse reactions and complications in the two groups (P>0.05). In conclusion, low-dose diuretics may effectively improve the cardiac and renal functions and prognosis in asymptomatic chronic HF patients, without increasing the incidence of side effects. PMID- 26668640 TI - Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway. AB - In the present study, we demonstrate that the degeneration of intervertebral discs is caused by ageing and apoptosis of matrix cells. Apoptosis is as essential as the function of proteoglycan synthesis in assessing the possible degeneration of intervertebral discs; paeoniflorin (PF) induces cytoprotective effects on various types of cells. In this study, the function of PF in inhibiting Fas ligand (FasL)-induced apoptosis in annulus fibrosus cells was assessed, and the correlation between apoptosis and the Fas-FasL pathway was determined. Annulus fibrosus cells were derived from the intervertebral discs of 1-month-old Sprague Dawley rats; the cells were characterised by toluidine blue staining and subjected to apoptosis with FasL. PF was diluted to various concentrations and added to annulus fibrosus cells at various times. The impact of PF and FasL on cell apoptosis of annulus fibrosus cells was determined by flow cytometry. Western blot analysis was performed to determine the protein expression levels of Fas and caspase-3. The percentages of apoptotic annulus fibrosus cells as well as the expression levels of caspase-3 and Fas were significantly reduced following treatment with 208, 20.8 or 2.08 uM PF. PF inhibits the activation of the Fas-FasL signal pathway and decreases FasL-induced apoptosis of annulus fibrosus cells. PMID- 26668641 TI - Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. AB - Cadmium (Cd) is a testicular toxicant and an endocrine disruptor in humans and rodents. The aim of the present study was to investigate the effects of paternal Cd exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. A total of 12 male rats were randomized into a control and Cd treated group (n=6 per group), and 12 female rats were administered distilled water and randomly divided into two groups (n=6 per group). Subsequently, sperm motility, viability, malformation rate of male rats and the neuromotor maturation, antioxidant ability, Cd accumulation in different organs of their offspring were measured. Compared with the control rats, the sperm motility rate and vitality were significantly reduced (P<0.01) and the sperm malformation rate was significantly increased (P<0.01) in the male rats following Cd treatment. Regarding the nervous system development of the offspring, the cliff-avoidance reflex, surface-righting reflex and negative geotaxis results exhibited significant differences between the Cd exposure and control groups (P<0.05). The Cd content in the liver and heart of the offspring of the Cd exposure rats was higher than that in the control rats (P<0.05), and the liver content peaked on postnatal day 21. Furthermore, Cd exposure affected the antioxidant activity of the offspring, which was shown by glutathione, malondialdehyde and superoxide dismutase assays. Collectively, the results indicate that Cd exposure affects the sperm quality of male rats and the neurobehavioral system of their offspring. PMID- 26668642 TI - Analysis of mutations of MDR3 exons 9 and 23 in infants with parenteral nutrition associated cholestasis. AB - The aim of this study was to investigate mutations of multidrug resistance 3 (MDR3) exons 9 and 23 in infants with parenteral nutrition-associated cholestasis (PNAC). A total of 41 infants with PNAC were enrolled in the study. Genomic DNA was extracted from the peripheral venous blood leukocytes of each patient and MDR3 exons 9 and 23 were amplified by polymerase chain reaction. One patient was identified who carried a frameshift mutation in MDR3 exon 23 (C.2793) that was caused by the insertion of a single adenine residue, while mutations were not found in MDR3 exon 23 in the other 40 patients. The clinical features of the patient with the MDR3 exon 23 frameshift mutation included high serum gamma glutamyl transferase levels, the absence of biliary dilatation and deformity in magnetic resonance cholangiopancreatography, and abnormal electrical capacitance tomography imaging of the liver. No mutations in MDR3 exon 9 were identified in any of the patients. All 41 PNAC patients recovered following oral ursodeoxycholic acid treatment. The C.2793 frameshift mutation in MDR3 exon 23 is potentially associated with the development of PNAC in infants. PMID- 26668643 TI - Evaluation of extrahepatic collateral arteries in hepatocellular carcinoma in three independent groups in a single center. AB - To improve the efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), this study evaluated the prevalence and causes of extrahepatic arteries (EHAs) and identified feeding arteries in HCCs in three independent clinical groups in a single inverventional radiology center. Between November 2011 and September 2012, 942 cases of HCC were included in this retrospective study. The patients were treated in three independent groups of 285, 301 and 356 patients, respectively. Enhanced computed tomography, enhanced magnetic resonance imaging and digital subtraction angiography were reviewed retrospectively and correlations between the presence of tumor-feeding EHAs and tumor number, size and location in the liver, number of repeat TACE procedures and complications were assessed. There were 698 EHAs in the 942 cases of HCC, with 182, 233 and 283 EHAs in the three independent groups, respectively. Tumor size was associated with EHA formation; the percentages of patients with EHAs were 2.7+/-3.0, 5.5+/-0.5, 43.2+/-4.0, 61.8+/-5.2 and 93.4+/-1.8% with tumor sizes of 2-3, 3-5, 5-7, 7-9 and >9 cm, respectively. There were 159+/-19 EHAs in each group feeding tumors in peripheral locations in the liver, but only 48.7+/ 6.8 in the central zone. The most common EHA was the right inferior phrenic artery, with a mean of 101.0+/-14.1 per group. The number of EHAs increased proportionally with the number of TACE sessions. The number of EHAs was positively associated with tumor size, peripheral location of the tumor and number of TACE sessions. PMID- 26668644 TI - Long-term outcomes of rotational atherectomy in coronary bifurcation lesions. AB - The aim of the present study was to determine the long-term outcomes of bifurcation lesions following a rotational atherectomy (ROTA). In this retrospective study, patients that had undergone a ROTA of the bifurcation coronary lesions in Juntendo University Hospital (Tokyo, Japan) were enrolled between January 2007 and December 2009, and received follow-up for a median duration of 48 months (range, 12-84 months). A total of 337 patients were enrolled. Each patient was treated with an average of 1.2+/-0.4 ROTA burrs (mean size, 2.9+/-0.3 mm). Baseline lesion length, reference diameter, minimal lumen diameter (MLD) and percentage of diameter stenosis (%DS) prior to the procedure were comparable between the DM and non-DM patients. Furthermore, MLD, %DS and acute gain following the procedure were similar between the two groups. At follow up, DM patients exhibited a significantly decreased MLD (1.97+/-0.92 vs. 2.26+/ 0.73 mm; P=0.0038), increased %DS (27.9+/-21.3 vs. 20.2+/-13.3%; P=0.022) and late loss (0.70+/-0.45 vs. 0.42+/-0.36 mm; P=0.0047) compared with the non-DM patients. Follow-up examinations (mean duration, 52.2+/-19.4 months) revealed that the DM patients experienced significantly higher rates of target lesion revascularization (TLR) [28 (15.7%) vs. 8 (5.0%); P=0.0011], target lesion (TL) restenosis [46 (25.8%) vs. 20 (12.6%); P=0.0019] and major adverse cardiac events (MACE) [36 (20.2%) vs. 19 (12.0%), P=0.039] compared with the non-DM patients. Although the usage of ROTA and drug-eluting stent evidently improved long-term outcomes in patients with bifurcation lesions, DM remained an independent risk factor for TLR, TL restenosis and MACE. Therefore, the management of DM in bifurcation lesions treated with ROTA requires increased investigation in future clinical practice. PMID- 26668645 TI - Chronic nerve injury-induced Mas receptor expression in dorsal root ganglion neurons alleviates neuropathic pain. AB - Neuropathic pain, which is characterized by hyperalgesia, allodynia and spontaneous pain, is one of the most painful symptoms that can be experienced in the clinic. It often occurs as a result of injury to the peripheral nerves, dorsal root ganglion (DRG), spinal cord or brain. The renin-angiotensin system (RAS) plays an important role in nociception. As an essential component of the RAS, the angiotensin (Ang)-(1-7)/Mas axis may be involved in antinociception. The aim of the present study was to explore the expression pattern of Mas in DRG neurons following chronic nerve injury and examine the effects of Mas inhibition and activation on neuropathic pain in a chronic constriction injury (CCI) rat model. The results showed, that compared with the sham group, CCI caused a time dependent induction of Mas expression at both the mRNA and the protein levels in DRG neurons. Consistent with the results, isolated DRG neurons showed a time dependent increase in Ang-(1-7) binding on the cell membrane following the CCI surgery, but not the sham surgery. Compared with the sham control groups, CCI significantly decreased the paw withdrawal latency and threshold, and this was markedly improved and aggravated by intrathecal injection of the selective Mas agonist Ang-(1-7) and the selective Mas inhibitor D-Pro7-Ang-(1-7), respectively. In conclusion, this study has provided the first evidence, to the best of our knowledge, that the Mas expression in DRG neurons is time-dependently induced by chronic nerve injury and that the intrathecal activation and inhibition of Mas can improve and aggravate CCI-induced neuropathic pain, respectively. This study has provided novel insights into the pathophysiological process of neuropathic pain and suggests that the Ang-(1-7)/Mas axis could be an effective therapeutic target for neuropathic pain, warranting further study. PMID- 26668646 TI - Effects of thymosin beta4 on a rat model of severe acute pancreatitis. AB - The aim of the present study was to investigate the effects of thymosin beta4 on a rat model of severe acute pancreatitis (SAP) induced by sodium taurocholate (STC) and the underlying mechanism. SAP was induced by the retrograde infusion of 5% STC (1 ml/kg) into the bile-pancreatic duct. In certain rats, thymosin beta4 (30 mg/kg) was administered intraperitoneally 30 min prior to the infusion of STC. The severity of pancreatitis was evaluated by the measurement of serum amylase, lipase, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and myeloperoxidase (MPO) levels, and histological grading. Nuclear factor (NF) kappaB activation was evaluated by immunohistochemistry and western blot analysis. Intercellular adhesion molecule (ICAM)-1 protein expression in the pancreas was studied using western blot analysis. Prophylactic administration of thymosin beta4 was found to attenuate serum amylase and lipase activity and the serum concentrations of proinflammatory cytokines. In addition, it attenuated pathological pancreatic injury, pancreatic MPO activity, and the activation of NF kappaB and ICAM-1 in the pancreas. These results suggest that thymosin beta4 exerts a protective effect against STC-induced pancreatic injury. PMID- 26668647 TI - Correlation analysis of severe aplastic anemia immunosuppressive therapy and human leukocyte antigen alleles in pediatric patients. AB - The aim of the present study was to investigate the correlation between the efficacy of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) and human leukocyte antigen (HLA) alleles. The polymerase chain reaction-sequence based typing high-resolution genotyping method was used to profile the HLA alleles of 115 SAA cases that were treated with rabbit antithymocyte globulin (r-ATG) + cyclosporine (CsA) immunosuppressive therapy and 222 normal control subjects. The aim was to compare the frequency distribution of HLA alleles among the IST-effective group, the IST-ineffective group and the healthy control group. The results showed that the gene frequencies (GFs) of HLA B*15:02, B*40:02, B*48:01, DRB1*09:01, C*01:02, C*03:04, DQB1*03:03 and DQB1*06:02 in the IST-effective group were significantly higher compared with those in the healthy control group, with a statistically significant difference. The GFs of HLA-B*15:11, B*38:01, B*39:05, DRB1*15:01, C*01:02 and C*08:22 in the IST-ineffective group were significantly increased compared with those in the healthy control group, with a statistically significant difference. The gene frequency of HLA-A*29:01 in the IST-effective group was significantly reduced compared with that in the IST-ineffective group, and the difference was statistically significant. In summary, IST efficacy in children with SAA that express the HLA-B*15:02, B*40:02, B*48:01, DRB1*09:01, C*01:02, C*03:04, DQB1*03:03 and DQB1*06:02 alleles may be superior, while the efficacy may be mitigated in children with SAA who express HLA-A*29:01, B*15:11, B*38:01, B*39:05, DRB1*15:01, C*01:02, C*08:22 alleles. PMID- 26668648 TI - In vitro analysis of the role of the mitochondrial apoptosis pathway in CSBE therapy against human gastric cancer. AB - The caper plant (Capparis spinosa L.) was a common Uyghur folk medicine, and is a member of the Capparidaceae family. In a previous study, the n-butanol extract of C. spinosa L. (CSBE) was demonstrated to exert anti-tumor activity; however, the underlying mechanism is currently not understood. The present study aimed to elucidate the mechanism underlying the CSBE-induced mitochondrial apoptotic pathway, in order to investigate the anti-tumor effects of this plant extract. CSBE-induced apoptosis of the SGC-7901 human gastric cancer cell line was observed, and alterations in the expression levels and localization of initiators, markers, and executors of the mitochondrial apoptosis pathway were analyzed. Following treatment of SGC-7901 cells with CBSE, proliferation was inhibited and apoptosis was induced; and these effects were associated with mitochondrial membrane potential disruption, cytochrome c release into the cytoplasm, and caspase-9 and caspase-3 activation. CSBE may have induced SGC-7901 cell apoptosis by upregulating the expression of B-cell lymphoma-2 (BCL-2) associated X protein, and downregulating the expression of BCL-2. The results of the present study suggested that CSBE may induce SGC-7901 cell apoptosis via activation of the mitochondrial apoptosis pathway. PMID- 26668649 TI - Cardiac shockwave therapy improves myocardial function in patients with refractory coronary artery disease by promoting VEGF and IL-8 secretion to mediate the proliferation of endothelial progenitor cells. AB - Cardiac shockwave therapy (CSWT) is a potential and effective remedy to promote revascularization in the ischemic myocardium of patients with refractory coronary heart disease (CHD). The technique is both safe and non-invasive; however, the underlying molecular mechanism remains unclear. The aim of this study was to evaluate the efficacy of CSWT in treating CHD patients and investigate a potential mechanism. A total of 26 patients with CHD were enrolled in the study, and CSWT was performed over a 3-month period. The efficacy of CSWT was assessed using several clinical parameters. Peripheral blood (PB) was collected prior to and following treatment. The number of circulating endothelial progenitor cells (EPCs) in the PB was counted using a flow cytometer, and the levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), stromal cell-derived factor 1 and matrix metalloproteinase 9 in the PB were analyzed. Mononuclear cells were isolated from the PB and cultured in vitro. The EPCs and EPC-colony forming units (EPC-CFUs) in the PB mononuclear cell culture were counted using an inverted phase contrast microscope. Following CSWT, the tested clinical parameters were significantly improved. The levels of circulating EPCs, VEGF and IL-8 in the PB were significantly increased, as were the EPCs and EPC-CFUs from the PB mononuclear cell culture. We suggest that EPC proliferation, mediated by VEGF and IL-8 secretion, may be among the potential mechanisms associated with CSWT. PMID- 26668650 TI - Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease. AB - Treatment of neonatal animals with capsaicin has previously been associated with long-lasting hyperthermia and severe cutaneous lesions. The present study analyzed the effects of capsaicin-induced hyperthermia on the occurrence of infectious disease and pruritic dermatitis in a rat model. Pregnant Sprague Dawley (SD) rats were obtained 1 week prior to parturition. Pups from each litter were randomly assigned to the following experimental groups: Capsaicin-treated (cap-treated; n=10) or vehicle-treated (n=5). Capsaicin (50 mg/kg) or vehicle were systemically administered to the SD rat pups (age, 48 h), after which body temperature was measured using a biotelemetry system, and the effects of hyperthermia on the ability of the rat pups to resist bacterial infection were analyzed. Furthermore, pruritus-induced scratching behavior and dermatitis were assessed, and changes in interleukin (IL)-4- and IL-13-induced immunoglobulin E expression were measured. Treatment of neonatal rats with capsaicin resulted in chronic hyperthermia, which had negative effects on the host immune defense response. The expression levels of T-helper type 2 cell-associated cytokines were significantly increased (P<0.01) in the cap-treated rats following bacterial infection with Staphylococcus aureus or Streptococcus agalactiae. Furthermore, cap-treated rats exhibited pruritus-induced scratching behavior and dermatitis. The results of the present study suggested that treatment of neonatal rats with capsaicin induces chronic hyperthermia and decreases the effectiveness of the host defense system. Therefore, a cap-treated neonatal rat model may be considered useful when investigating the association between hyperthermia and infectious disease. PMID- 26668651 TI - Use of high-resolution 3.0-T magnetic resonance imaging to characterize atherosclerotic plaques in patients with cerebral infarction. AB - The present study aimed to evaluate the utility of high-resolution magnetic resonance imaging (MRI) in the characterization of atherosclerotic plaques in patients with acute and non-acute cerebral infarction. High-resolution MRI of unilateral stenotic middle cerebral arteries was performed to evaluate the degree of stenosis, the wall and plaque areas, plaque enhancement patterns and lumen remodeling features in 15 and 17 patients with acute and non-acute cerebral infarction, respectively. No significant difference was identified in the vascular stenosis rate between acute and non-acute patients. Overall, plaque eccentricity was observed in 29 patients, including 13 acute and 16 non-acute cases, with no significant difference identified between these groups. The wall area of stenotic arteries and the number of cases with plaque enhancement were significantly greater in the acute patients, but no significant difference in plaque or lumen area was identified between the 2 patient groups. Lumen remodeling patterns of stenotic arteries significantly differed between the acute and non-acute patients; the former predominantly demonstrated positive remodeling, and the latter group demonstrated evidence of negative remodeling. In conclusion, patients with acute and non-acute cerebral infarction exhibit specific characteristics in stenotic arteries and plaques, which can be effectively evaluated by high-resolution MRI. PMID- 26668652 TI - Airway loss during inhalation induction of anesthesia with sevoflurane in a pediatric patient with laryngeal papillomatosis: A case report. AB - The aim of the present study was to report a failed inhalation induction of anesthesia with sevofluran in a pediatric patient with grade III laryngeal obstruction caused by laryngeal papillomatosis. Inhalation induction is recommended for the induction of anesthesia in pediatric patients. In the present case, due to the respiratory depression properties of the anesthetics, the partial airway obstruction developed into complete airway obstruction, followed by cardiac arrest. The patient survived after the surgeon managed to reconvert the complete airway obstruction into partial airway obstruction through the removal of part of the laryngeal papillomas. In conclusion, the reaction of the patient in the present case to sevoflurane inhalation induction suggests that this technique is not recommended for patients with pre-existing severe airway obstruction. In such cases, special consideration and preparation is required. PMID- 26668653 TI - Novel keratin 5 mutation in a family with epidermolysis bullosa simplex. AB - The aim of the present study was to identify the causative gene defects associated with epidermolysis bullosa simplex (EBS) in a pedigree. The diagnosis of EBS was confirmed in two patients from that pedigree based on the clinical manifestations, histopathological examination of the skin and family history. Blood samples were collected from 6 family members and 100 heathy controls, and genomic DNA and RNA were extracted. Mutation analysis of the keratin 5 gene (KRT5) was conducted using polymerase chain reaction (PCR) direct sequencing and PCR-restriction fragment length polymorphism. In the pedigree, the results of PCR direct sequencing revealed a heterozygous missense mutation in codon 202 of exon 2 of KRT5 (c.605T>A), which led to an amino acid change (p.L202Q) in the patients with EBS but was absent from the unaffected family members and 100 population controls. In conclusion, a novel missense mutation in the KRT5 gene was identified that had a pathogenic role in EBS in the population studied, which enriches the germline mutation spectrum of the KRT5 gene. PMID- 26668654 TI - Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells. AB - Previous studies have demonstrated that the expression levels of cytokines are increased in degenerated intervertebral disc tissues, and several cytokines are associated with the pathogenesis of intervertebral disc degeneration. However, the role of interleukin (IL)-2 in the cellular functions of intervertebral disc tissues remains unreported. The present study aimed to determine the expression levels of IL-2 in the nucleus pulposus (NP) tissues of patients with a prolapsed lumbar intervertebral disc; and to observe the changes in cell proliferation, apoptosis, extracellular matrix (ECM) metabolism and p38 mitogen-activated protein kinase (MAPK) signaling in human NP cells (HNPCs) following treatment with IL-2. The present study demonstrated that IL-2 expression levels were upregulated in the NP tissues of patients with a prolapsed lumbar intervertebral disc; and a subsequent MTT assay demonstrated that IL-2 inhibits the proliferation of HNPCs in a dose-dependent manner. Furthermore, as demonstrated by the increased protein expression levels of Fas cell surface death receptor and the induction of caspase-8 and caspase-3 activity, the death receptor pathway was activated by IL-2 in the HNPCs in order to promote cell apoptosis. In addition, IL-2 promoted ECM degradation in the HNPCs, as demonstrated by an increase in the expression levels of type I collagen, a disintegrin and metalloproteinase with thrombospondin motifs and matrix metalloproteinases, and decreased aggrecan and type II collagen expression levels. Furthermore, phosphorylated-p38 was significantly increased in the HNPCs following IL-2 treatment. In conclusion, the present study demonstrated that IL-2 inhibits cell proliferation, and induces cell apoptosis and ECM degradation, accompanied by the activation of p38 MAPK signaling in HNPCs. Therefore, IL-2 may be a potential therapeutic agent for the treatment of degenerative disc disease. PMID- 26668655 TI - Pediatric sinonasal rhabdomyosarcoma: A case report. AB - Pediatric sinonasal rhabdomyosarcoma (PSR) is a rare condition, with a limited number of previously reported cases. It is an aggressive malignancy associated with poor outcomes, and no consensus has been reached on the optimal therapeutic strategy. The present study reported the case of embryonal PSR in a 2-year old girl, presenting with unilateral nasal obstruction and a polypoid mass protruding from the left nasal cavity. The pediatric patient was initially treated with surgical resection, followed by adjuvant chemotherapy containing vincristine (1.5 mg/m2, weekly) and actinomycin-D (1.5 mg/m2, three times weekly). On the 10th month of follow-up, tumor recurrence was detected and a salvage surgery was performed, while the same chemotherapy regimen was resumed. Following the first cycle of chemotherapy, the patient developed a fungal bronchopneumonia and succumbed due to disease progression, acute respiratory distress syndrome and septic shock 12 months after diagnosis. PMID- 26668656 TI - CORRIGENDUM. AB - [This corrects the article DOI: 10.3892/etm.2015.2659.]. PMID- 26668657 TI - Assessment of the Antimicrobial Activity of Few Saudi Arabian Snake Venoms. AB - BACKGROUND: Venoms of two cobras, four vipers, a standard antibiotic and an antimycotic, were evaluated comparatively, as antimicrobials. METHODS: Six venom concentrations and three of the standard antibiotic and the antimycotic were run in micro-dilution and diffusion plates against the microorganisms. RESULTS: Echis pyramidum, Echis coloratus and Cerastes cerastes gasperettii highest venom concentrations gave significant growth inhibition zones (GIZ) with respect to a negative control, except Bitis arietans, whose concentrations were significant. The cobra Walterinnesia aegyptia had significant venom concentrations more than Naja haje arabica. The Staphylococcus aureus Methicillin Resistant (MRSA) bacterium was the most susceptible, with a highly (P < 0.001) significant GIZ mean difference followed by the Gram positive Staphylococcus aureus, (P < 0.001), Escherichia coli (P < 0.001), Enterococcus faecalis (P < 0.001) and Pseudomonas aeruginosa which, had the least significance (P < 0.05). The fungus Candida albicans was resistant to both viper and cobra venoms (P > 0.05). The antibiotic Vancomycin was more effective than snake venoms though, they were more efficient in inhibiting growth of the resistant Pseudomonas aeruginosa. This antibiotic was also inactive against the fungus, whilst its specific antifungal Fungizone was highly efficient with no antibacterial activity. CONCLUSIONS: These findings showed that snake venoms had antibacterial activity comparable to antibiotics, with a directly proportional relationship of venom concentration and GIZ, though, they were more efficient in combatting resistant types of bacteria. Both venoms and the standard antibiotic, showed no antifungal benefits. PMID- 26668658 TI - Assessment of Microbial Load of Un-pasteurized Fruit Juices and in vitro Antibacterial Potential of Honey Against Bacterial Isolates. AB - The development of resistance in bacteria against commonly used antibiotics/drugs is of considerable medical significance. Aim of this study was to determine the microbial load of un-pasteurized packed fruit juices sold in Lahore city and to determine antibacterial activity of five different honey samples against isolated bacteria. Unpasteurized fruit juice samples (n=60) were collected from street vendors. All the samples were subjected to Total viable count (TVC), Staphylococcal count (SC) and Coliform count (CC). One hundred and ten strains of bacteria were isolated from various fruit juices and identified on the basis of cultural characters, morphology and biochemical characters. Mean TVCs, SCs and CCs of juices (6.80+/-1.91, 5.45+/-1.06 and 3.25+/-1.25 log10 CFU/ml respectively) were non-significant with standard permissible limits (p<0.05). Among all the fruit juices, 66.66% of samples had TVC more than 4 log10 CFU/ml, 51.66% of samples had SC more than 3 log10 CFU/ml and 46.66% of samples had CC more than 2 log10 CFU/ml. Among the bacillus isolates purified, were Bacillus alvei, Bacillus subtilis, Bacillus polymyxa, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli and Enterobecter. All five different types of honey samples used in this study showed antibacterial activity against B. alvei, B. polymyxa, B. subtilis and S. aureus and no activity against P. aeruginosa, K. pneumonia, Enterobecter and E. coli. It is concluded that microbial load in unpasteurized fruit juices is significantly higher than standard permissible limits which insinuates its possible role in spoilage and food borne illnesses. Periodic monitoring of packed fruit juices should be carried out to make them safe for consumption. Honey can be used as an alternative for treatment of various infections, especially those caused by antibiotic resistant bacteria. PMID- 26668659 TI - Challenges in the Laboratory Diagnosis and Management of Dengue Infections. AB - Dengue fever is considered the most important arthropod-borne viral diseases in terms of morbidity and mortality. An accurate and efficient diagnosis of dengue plays an important role in case confirmation. The virus may be isolated during the viremic phase (within day 5 of illness), from serum, plasma and peripheral blood mononuclear cells. Enzyme linked immunoassay (ELISA) has demonstrated the presence of high levels of dengue NS1 antigen and tests may be performed by enzyme-immunoassays (EIAs) or immune-chromatographic (ICT) methods. These assays are specific with respect to different flaviviruses. Conventional and real time RT PCR, nested PCR, multiplex PCR and Nucleic acid sequence based amplification (NASBA) have been described as sensitive and relatively rapid method of detecting the virus during the early viremic phase. Other tests used include assay of anti dengue specific IgM and IgG ELISA. Currently no curative treatment in terms of anti-viral drugs is available for dengue and patients are managed with rest and aggressive supportive therapy. Management may be done at home or in the hospital depending on the severity of the illness. Hospital management includes fluid therapy, blood component transfusion and other modalities of treatments like steroids, recombinant factor VII and management of complications. Various vaccines are in trial stages and may become available in the near future. PMID- 26668660 TI - Molecular Identification of Mycobacterium Species of Public Health Importance in Cattle in Zimbabwe by 16S rRNA Gene Sequencing. AB - Mycobacterium species are naturally found in the environment as well as in domestic animals such as cattle. So far, more than 150 species of Mycobacterium, some of which are pathogenic, have been identified. Laboratory isolation, detection and identification of Mycobacterium species are therefore critical if human and animal infections are to be controlled. The objective of this study was to identify Mycobacterium species isolated in cattle in Zimbabwe using 16S ribosomal RNA gene amplification and sequencing. A total of 134 cow dung samples were collected throughout Zimbabwe and mycobacteria were isolated by culture. Only 49 culture isolates that were found to be acid-fast bacilli positive by Ziehl-Neelsen staining. The 16S rRNA gene was successfully amplified by PCR in 41 (84%) of the samples. There was no amplification in 8 (16%) of the samples. Out of the 41 samples that showed amplification, 26 (63%) had strong PCR bands and were selected for DNA sequencing. Analysis of the DNA sequences showed that 7 (27%) belonged to Mycobacterium neoaurum, 6 (23%) belonged to Mycobacterium fortuitum, 3 (12%) to Mycobacterium goodii, 2 (1%) to Mycobacterium arupense, 2 (1%) to Mycobacterium peregrinum or M. septicum and 1 isolate (0.04%) to Mycobacterium elephantis. There were 5 (19%) isolates that were non-mycobacteria and identified as Gordonia terrae, a close relative of Mycobacterium. The study therefore provided a molecular basis for detection and identification of Mycobacterium species in animals and humans. PMID- 26668661 TI - Seroepidemiological Survey of Canine Leishmania Infections from Peripheral Areas in Natal, Northeast Brazil. AB - BACKGROUND AND OBJECTIVE: Human visceral leishmaniasis is endemic in Natal, northeast of Brazil, where the domestic dog is an important parasite reservoir in the infectious cycle of Leishmania spp. In this study, was evaluated the antileishmanial IgG antibody and epidemiological factors related to canine visceral leishmaniasis (CVL). METHODS: Sera samples obtained by venipuncture of 1,426 dogs living in areas of human visceral leishmaniasis occurrence were tested for detection of IgG anti-leishmania antibodies with Immunofluorescence Antibody Assay (IFA) and Enzyme Linked Immunosorbent Assay (ELISA). Chi-square (x(2)) and Odds Ratio (OR) were calculated. Differences were considered statistically significant at p<=0.05. RESULTS: The overall seroprevalence was 10.30% (147/1,426); prevalence increased when the samples were found to be positive at least for one technique ([417/1,426] 29.3%). The high percentage of seroprevalence was observed in Nova Republica (15.35%), Nova Natal I (12.7%) and Lagoa Azul (11.4%) neighborhoods. In the Planalto, Soledade and Brasil Novo, the infection rates ranged from 7.5 at 8.06%. (p=0.00051). There was neither statistically significant difference between leishmanial infection nor clinical signs of disease (p=0.84; OR=1.0 [0.41; 2.3]), sex (p=0.78, OR=0.94 [0.66; 1.28]); and breed (p=0.92; OR=1.0 [0.65; 1.54]) were observed. CONCLUSION: The RESULTS suggest that CVL is widely distributed in Natal, may be increasingly urbanizing and will spread through neighborhoods but not endemic, resulting in a serious public health problem, emphasizing the need for epidemiological studies to a greater understanding of the distribution of canine leishmaniasis in these specific areas and contribute proactively to the public health policies. PMID- 26668662 TI - Immobilization of Microbes for Bioremediation of Crude Oil Polluted Environments: A Mini Review. AB - Petroleum hydrocarbons are the most common environmental pollutants in the world and oil spills pose a great hazard to terrestrial and marine ecosystems. Oil pollution may arise either accidentally or operationally whenever oil is produced, transported, stored and processed or used at sea or on land. Oil spills are a major menace to the environment as they severely damage the surrounding ecosystems. To improve the survival and retention of the bioremediation agents in the contaminated sites, bacterial cells must be immobilized. Immobilized cells are widely tested for a variety of applications. There are many types of support and immobilization techniques that can be selected based on the sort of application. In this review article, we have discussed the potential of immobilized microbial cells to degrade petroleum hydrocarbons. In some studies, enhanced degradation with immobilized cells as compared to free living bacterial cells for the treatment of oil contaminated areas have been shown. It was demonstrated that immobilized cell to be effective and is better, faster, and can be occurred for a longer period. PMID- 26668663 TI - Model-based Characterization of the Parameters of Dissimilatory Sulfate Reduction Under the Effect of Different Initial Density of Desulfovibrio piger Vib-7 Bacterial Cells. AB - The objective of this study was to design a model of dissimilatory sulfate reduction process using the Verhulst function, with a particular focus on the kinetics of bacterial growth, sulfate and lactate consumption, and accumulation of hydrogen sulfide and acetate. The effect of the initial density (0.12+/-0.011, 0.25+/-0.024, 0.5+/-0.048 and 1.0+/-0.096 mg cells/ml of medium) of the sulfate reducing bacteria Desulfovibrio piger Vib-7 on the growth and dissimilatory sulfate reduction was studied. The exponential growth phase of the D. piger Vib-7 was observed for 72 hours of cultivation at the (0.12 and 0.25 mg/ml) initial concentration of bacterial cells. Sulfate and lactate were consumed incompletely during this time. The increase in the initial concentration of cells to 0.5 and 1 mg/ml led to a shortening of the exponential bacterial growth phase and a shift to the stationary phase of the growth. In the case of 0.5 mg/ml seeding, the stationary growth phase was observed in the 36(th) hour of cultivation. The increase in the initial concentration of cells to 1 mg/ml led to the beginning of the stationary growth phase in 24th hours of cultivation. Under these conditions, sulfate and lactate were consumed completely in the 48th hour of cultivation. The kinetic analysis of the curves of bacterial growth and the process of dissimilatory sulfate reduction by D. piger Vib-7 was carried out. PMID- 26668664 TI - Preparation of Specific Polyclonal Antibody Against the Recombinant Mutacin Produced by sfGFP Fusion Protein Technology. AB - Mutacin I, a bacteriocin produced by streptococcus mutans, displays an antimicrobial activity against many gram positive and some gram negative bacteria. Because of its medical importance, production of this short peptide in large scale for future applications is a significant challenge. This work described the improvement of a novel system to produce the recombinant mutacin using fusion protein technology. The short peptide was expressed directly as a fusion protein with a superfolder form of the green florescent protein (sfGFP), resulting in a high yield expression of soluble sfGFP-mutacin fusion protein (30 kDa) in the cytoplasm of E. coli. Mutacin was released from the fusion by enzymatic cleavage at the tobacco etch virus (TEV) protease recognition site and separated from the carrier sfGFP by nickel affinity and gel filtration chromatography. An additional advantage of this fusion system was tested in the generation of mutacin-specific polyclonal antibodies. Specific anti-mutacin IgGs were affinity purified, and were able to recognize the mutacin-sfGFP fusion protein or the cleaved forms of mutacin. Even though it was efficiently produced (25 mg/L) by this method, pure mutacin was devoid of antibiotic activity. Fourier transform infrared spectroscopy (FTIR) analysis revealed the absence of thioether bonds in the purified mutacin, which are critical for final structure and function of this antibiotic. Determining whether the activity of pure mutacin could be recovered by the reformation of such structures by chemical reaction needs more investigations. The development of this system will provide large quantities of mutacin for future studies and applications as broad spectrum antibacterial peptide. PMID- 26668665 TI - Listeriolysin O, but not Murine E-cadherin, is Involved in Invasion of Listeria monocytogenes into Murine Liver Parenchymal Cells. AB - Human E-cadherin and listeriolysin O (LLO) are involved in invasion of Listeria monocytogenes into human liver parenchymal cells (LPC). Yet, it remains to be determined whether murine E-cadherin and LLO participate in invasion of L. monocytogenes into murine LPC. In the present study, involvement of murine E cadherin and LLO in invasion of L. monocytogenes into murine LPC was investigated. Murine E-cadherin was expressed on murine LPC, but the expression became undetectable by insertion of transgene of Simian virus 40 large T antigen. Although invasion of L. monocytogenes into murine LPC was found regardless of murine E-cadherin expression, infection rate of L. monocytogenes being unable to secrete LLO was lower than that of L. monocytogenes being capable of secreting LLO. Our RESULTS verify that invasion of L. monocytogenes into murine LPC occurs independently of murine E-cadherin and indicate that LLO participates in invasion of L. monocytogenes into murine LPC. PMID- 26668666 TI - Drug-likeness of Phytic Acid and Its Analogues. AB - Inositol hexakisphosphate is known to be the phosphorous reserve in plants particularly in the seeds. Though it has been known for its antinutrient properties for many years, recent research shed light to reveal it as a novel anticancer agent. Hence the present study investigates the drug-likeness of phytic acid and its analogues through bioinformatics methods. Two potential cancer drug targets such as mitogen activated kinase and inositol 1,4,5 triphosphate receptor are included in the study. Out of 50 selected analogues of phytic acid, 42 structures interact well with the chosen drug targets. The best interacting structures are 1-diphosinositol pentakisphosphate and 2,3,4,5,6 pentaphosphonooxycyclohexyl dihydrogen phosphate. For both of these structures, the negative binding energy obtained was -49.5 KJ/mol; this affirms the stability of the complex. ADME properties are also predicted to assess the drug-like properties of the compounds. The structure activity relationship model is generated for 12 compounds with experimental IC50 values. PMID- 26668667 TI - High Diagnostic Accuracy of Nitrite Test Paired with Urine Sediment can Reduce Unnecessary Antibiotic Therapy. AB - BACKGROUND: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy. AIMS: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy. METHODS: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI. RESULTS: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was >=4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT >=4h and six patients at <=3h or overall. CONCLUSION: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance. TRIAL REGISTRATION: The Swedish Medical Product Agency 1995 03 01:151:01783/94. PMID- 26668668 TI - Molecular Analysis of the Cyanobacterial Community in Gastric Contents of Egrets with Symptoms of Steatitis. AB - Many deaths of wild birds that have drunk water contaminated with hepatotoxic microcystin-producing cyanobacteria have been reported. A mass death of egrets and herons with steatitis were found at the agricultural reservoir occurring cyanobacterial waterblooms. This study aimed to verify a hypothesis that the egrets and herons which died in the reservoir drink microcystin-producing cyanobacteria and microcystin involves in the cause of death as well as the symptoms of steatitis. The cyanobacterial community in gastric contents of egrets and herons that died from steatitis was assessed using cyanobacterial 16S rRNA based terminal-restriction fragment length polymorphism (T-RFLP) profiling and a cyanobacterial 16S rRNA-based clone library analysis. In addition, PCR amplification of the mcyB-C region and the mcyG gene, involved in microcystin biosynthesis, was examined. The cyanobacterial community in the gastric contents of two birds showed a simplistic composition. A comparison of cyanobacterial T RFLP profiling and cloned sequences suggested that the genus Microcystis predominated in both samples of egrets died. Although we confirmed that two egrets which died in the reservoir have taken in cyanobacterial waterblooms containing the genus Microcystis, no mcy gene was detected in both samples according to the mcy gene-based PCR analysis. This study is the first to show the profiling and traceability of a cyanobacterial community in the gastric contents of wild birds by molecular analysis. Additionally, we consider causing symptoms of steatitis in the dead egrets. PMID- 26668669 TI - The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment. AB - Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID- 26668670 TI - Intravenous Immune Globulin in Amyopathic Dermatomyositis - Report of Two Cases and Review of the Literature. AB - Amyopathic dermatomyositis (ADM) is a rare subtype of dermatomyositis which is often recalcitrant to immune suppressing treatments. Intravenous immunoglobulin (IVIG) has been used in the treatment of refractory dermatomyositis. We present two patients with severe ADM, who were treated with IVIG at 2 g/kg every four weeks. Both patients had a successful response and were able to taper the dosage of prednisone. We present both cases in describing IVIG as a rescue and maintenance steroid-sparing agent in the treatment of severe refractory ADM. We also review the treatment of refractory ADM with IVIg in the English literature. PMID- 26668672 TI - Analysis of aceclofenac and bovine serum albumin interaction using fluorescence quenching method for predictive, preventive, and personalized medicine. AB - BACKGROUND: The study of the interaction of a drug with plasma protein is very important because drug-protein binding plays an important role in determination of pharmacological and toxicological properties of drugs. Our study was designed to investigate the interaction between aceclofenac and bovine serum albumin (BSA) using fluorescence spectroscopy at different temperatures (298 and 308 K). METHODS: Fluorescence spectroscopy was used to carry out the study. Fluorescence quenching constant was determined from Stern-Volmer equation. Van't Hoff equation was used to determine the thermodynamic parameters such as free energy (DeltaG), enthalpy (DeltaH), and entropy (DeltaS). RESULTS: The experimental data showed that the quenching of BSA by aceclofenac was due to a formation of a BSA aceclofenac complex with probable involvement of both tryptophan and tyrosine residues of BSA. Dynamic quenching was shown for BSA by aceclofenac at the experimental conditions. The values of thermodynamic parameters indicated that the hydrophobic forces played major roles for BSA-aceclofenac complexation. The binding number (n) was found to be ~1 indicating that 1 mol of BSA bound with 1 mol of aceclofenac. The binding affinity of aceclofenac to BSA was calculated at different temperatures. It was shown that the binding constant decreased with increasing temperatures indicating that stability of the BSA-aceclofenac complex decreased with increasing temperatures. CONCLUSIONS: The interaction of aceclofenac with BSA was successfully explored using a fluorescence spectroscopic technique. PMID- 26668671 TI - Condom Use Determinants and Practices Among People Living with HIV in Kisii County, Kenya. AB - The male condom remains the single, most efficient and available technology to reduce sexual transmission of HIV as well as sexually transmitted infections. This study sought to establish condom use determinants and practices among people living with HIV (PLHIVs) in Kisii County, Kenya. We interviewed 340 PLHIVs and 6 health workers. Although most PLHIVs had correct knowledge and approved condoms as effective for HIV prevention, consistent use and condom use at last sex were notably low especially among PLHIVs aged 18 - 24, those who depended on remittances from kin as main source of income, as well as during sex with secondary and casual partners. This study notes that knowledge on various benefits of using condoms is associated with enhanced condom use practices. Non disclosure of HIV status to secondary and casual partners remains a key barrier to condom use among PLHIVs Our observations highlight the need to further promote condom use among specific PLHIVs socio-demographic groups who continue to exhibit low condom use rates. PMID- 26668673 TI - Avoiding Common Writing Mistakes That Make Your Editors and Reviewers Cringe. AB - Writing for scientific journals is not an inherently simple task for most people. It requires purposeful effort and multiple revisions of the initial manuscript draft. While each author and article has its own individuality, writing well to address the core elements of a scientific report is necessary. As editors of the IJTMB, we often see weaknesses in the core elements of the manuscripts we receive. This editorial summarizes common recurring issues, and provides suggestions on how to avoid these pitfalls in the submission of a research article or case report to the IJTMB. PMID- 26668674 TI - The Use of an Informational Video to Improve Patient Satisfaction, Preparedness, Mood, and Empowerment. AB - BACKGROUND: Massage therapy is commonly used in Canada for the treatment of a wide range of health concerns. Massage therapy is changing to meet the health care needs of Canadians. Rapid changes to the profession may create a gap between patient expectations of massage therapy treatment based on historic views of the profession and their experience in today's practice. This gap could lead to patient confusion, dissatisfaction, or other negative outcomes. PURPOSE: This study sought to understand whether patient satisfaction, preparedness, mood, and patient empowerment are improved when new patients who attend a student massage therapy clinic watch an informational video, compared to those who receive the standard paper information sheet. PARTICIPANTS: The study used a convenience sample of new patients who presented for their first massage therapy appointment to the Humber College Student Massage Therapy Clinic. Participants were randomized either to the intervention group (video and paper information) or the comparison group (paper information only). The outcomes of interest in this study were patient preparedness, satisfaction, mood, and empowerment. Data were collected using two questionnaires, one before treatment and one after. RESULTS: A total of 108 patients participated in the study (55 comparison group; 53 intervention group). Demographic and clinical characteristics were comparable between the two groups. A statistically significant difference was seen between the two groups when comparing their responses to the pre-appointment statement: "I know what will happen in my initial massage therapy appointment" (p < .001). There was no statistically significant difference seen when comparing the responses of the related post-appointment statement (p = .63). CONCLUSION: This study found that an informational video improved perceived knowledge as patients entered the massage therapy treatment, but did not have a significant effect on satisfaction, mood, or patient empowerment. Other student clinics should consider the addition of an informational video to their procedures to increase patient knowledge of what to expect. PMID- 26668675 TI - Erratum: Practice and Research in Australian Massage Therapy: a National Workforce Survey. PMID- 26668676 TI - Systematic Literature Review on ICF From 2001 to 2013 in the Nordic Countries Focusing on Clinical and Rehabilitation Context. AB - We present a systematic review on International Classification of Functioning, Disability and Health (ICF) used in the Nordic countries from 2001 through 2013, describing and quantifying the development in utilization of ICF, and describe the extent to which the different components of the ICF have been used. A search was conducted in EMBASE, MEDLINE and PsycInfo. Papers from Nordic countries were included if ICF was mentioned in title or abstract. Papers were assigned to one of eight categories covering the wide rehabilitation area; furthermore, area of focus was assigned. Use of ICF components and intervention were coded in papers categorized as "clinical and/or rehabilitation contexts" or "non-clinical contexts". One hundred seventy papers were included, of these 99 papers were from the categories "clinical and/or rehabilitation contexts" or "non-clinical contexts". Forty-two percent of the 170 included papers were published in the period 2011 - 2013. There was an increase in ICF-relevant papers from 2001 to 2013, especially in the categories "clinical and/or rehabilitation contexts" and "non-clinical contexts". The most represented focus areas were neurology, musculoskeletal, and work-related areas. All five or at least four ICF components were mentioned in the results or discussions in most papers, and activity was most frequently mentioned. PMID- 26668677 TI - Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering. AB - The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown. PMID- 26668678 TI - Repeatability and Diagnostic Value of Nasal Potential Difference in a Genetically Admixed Population. AB - BACKGROUND: The genetic diversity of the Brazilian population results from three ethnic groups admixture: Europeans, Africans and Amerindians, thus increasing the difficulty of performing cystic fibrosis (CF) diagnosis. The nasal potential difference (NPD) evaluates the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. Despite being a useful CF diagnostic test and a biomarker of CFTR-modulator drugs, it is also highly operator dependent. Therefore, it may be difficult to get accurate results and to interpret them. Wilschanski and Sermet scores were proposed to address these issues. This study aimed to evaluate repeatability and diagnostic value of NPD parameters and Wilschanski and Sermet scores in a CF center in Rio de Janeiro. METHODS: NPD was performed in 78 subjects. Maximal PD, amiloride response, total chloride response, and Wilschanski and Sermet scores were explored as means (confidence interval, CI). One-way ANOVA was used to compare mean differences and Scheffe test was used to pair-wise comparisons. Repeatability was evaluated by scatter and Bland-Altman plots. The Ethics Committee of the CF Center has approved the study protocol. Parents and adult participants signed an informed consent form. RESULTS: Forty-eight healthy volunteers, 19 non-CF and 11 CF patients were enrolled in this study. Significant differences were found when comparing CF patients' NPD parameters to the other two groups (P = 0.000). Moreover, no significant differences were found when parameters from non-CF patients were compared with those from healthy volunteers (P > 0.05). The means of NPD parameters and diagnostic scores of each group were in concordance with disease/non-disease conditions. The repeatability data - Wilschanski and Sermet and NPD - allow NPD to be performed in this Brazilian CF Center. CONCLUSIONS: The present study gathered consistent data for Bland-Altman plots. The results of Wilschanski and Sermet diagnostic scores suggest that they were concordant with CF/non-CF conditions. More NPD tests should be performed in the Rio de Janeiro CF dynamic cohort to contribute to international NPD validation studies and to provide NPD as a biomarker in Brazil. PMID- 26668679 TI - Leptospira Exposure and Gardeners: A Case-Control Seroprevalence Study. AB - BACKGROUND: Leptospira can be found in soil. However, it is unclear whether occupational exposure to soil may represent a risk for Leptospira infection in humans. Therefore, we sought to determine the association of Leptospira IgG seroprevalence with the occupation of gardener, and to determine the epidemiological characteristics of gardeners associated with Leptospira exposure. METHODS: We performed a case-control study in 168 gardeners and 168 age- and gender-matched control subjects without gardening occupation in Durango City, Mexico. The seroprevalence of anti-Leptospira IgG antibodies in cases and controls was determined using an enzyme immunoassay. Bivariate and multivariate analyses were used to assess the association of Leptospira exposure and the characteristics of the gardeners. RESULTS: Anti-Leptospira IgG antibodies were found in 10 (6%) of 168 gardeners and in 15 (8.9%) of 168 control subjects (odds ratio (OR): 0.64; 95% confidence interval (CI): 0.28 - 1.48; P = 0.40). Multivariate analysis showed that Leptospira seropositivity was positively associated with female gender (OR: 5.82; 95% CI: 1.11 - 30.46; P = 0.03), and negatively associated with eating while working (OR: 0.21; 95% CI: 0.05 - 0.87; P = 0.03). In addition, multivariate analysis showed that high anti-Leptospira levels were associated with consumption of boar meat (OR: 28.00; 95% CI: 1.20 - 648.80; P = 0.03). CONCLUSIONS: This is the first case-control study of Leptospira exposure in gardeners. Results do not support an association of Leptospira exposure with the occupation of gardener. However, further studies to confirm the lack of this association are needed. The potential role of consumption of boar meat in Leptospira infection deserves further investigation. PMID- 26668680 TI - The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis. AB - BACKGROUND: Limited data exist regarding impact of IDH mutations in Philadelphia negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). METHODS: High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. RESULTS: PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. CONCLUSIONS: We conclude that IDH mutations indicate a risk for leukemic transformation in PMF. PMID- 26668681 TI - Secular Trends in Utilization of Critical Care Services Among Candidemia Associated Hospitalizations: A Population-Based Cohort Study. AB - BACKGROUND: The incidence of candidemia continues to rise in recent years. Candidemic patients often require care in an intensive care unit (ICU) and can consume substantial resources. However, there are no contemporary longitudinal population-level data on the incidence patterns of ICU utilization among patients with candidemia in the United States. METHODS: The Texas Inpatient Public Use Data File was used to identify hospitalized patients aged >= 18 years for the years 2001 - 2010. Hospitalizations with candidemia were identified by presence of an International Classification of Diseases, Ninth Revision, Clinical Modification Code 112.5. The annual rates of ICU admission among candidemia hospitalizations were examined. The annual incidence of candidemia hospitalizations with admission to ICU (C-ICU) was evaluated using the United States Census data, and was also benchmarked against the number of all hospitalizations and hospitalizations with ICU admission, overall and for age specific strata. RESULTS: There were 11,544 hospitalizations with candidemia, including 7,552 (65.4%) with C-ICU. Between 2001 and 2010, the rate of C-ICU among hospitalizations with candidemia increased from 60.2% to 68.0%, and the incidence of C-ICU increased by 91%, rising from 2.73 to 5.21 per 100,000 population. When benchmarked against hospital admissions and ICU admissions, the following changes were noted between 2001 and 2010 in the incidence of C-ICU: 1.61 vs. 3.34 per 10,000 hospitalizations, and 8.33 vs. 13.77 per 10,000 hospitalizations with ICU admission. The incidence of C-ICU rose rapidly during the first half of the last decade, while plateauing during the remainder of study period. There has been marked difference in the rate of rise in the incidence of C-ICU among examined age strata, being highest among the 18 - 44 year group. CONCLUSIONS: ICU care occurred in the majority of candidemia hospitalizations. The incidence of C-ICU rose nearly two-fold during study period, but the rise plateaued during the second half of the last decade. Substantial heterogeneity was noted in the rate of rise in the incidence of C-ICU across examined age groups. Further study in other populations is required to corroborate our findings and examine the sources of the observed trends. PMID- 26668682 TI - Defibrillator-Induced Tricuspid Abscess Presenting as Diabetic Ketoacidosis and Wound Ulceration. AB - Right-sided endocarditis is predominantly seen in patients with a history of intravenous drug abuse. However, it is well shown in the literature to be associated with patients containing foreign bodies such as pacemakers, central venous lines, and in those with congenital heart disease. In patients with pacemaker leads and in those with automatic implantable cardioverter defibrillators (AICDs), it is important to suspect foreign body infection when there are signs and indications of bacteremia. When these leads become infected, they can spread the infection to the tricuspid valve resulting in vegetations. The proper management is removal of the infected lead and foreign body along with a prolonged course of antibiotics. However, it is unusual and a relatively rare entity to see foreign body infection resulting from a wound ulcer resulting in not only endocarditis but also abscess formation on the tricuspid valve. Here we report a case of a 60-year-old male with recent AICD placement presenting as diabetic ketoacidosis due to tricuspid abscess formation as a result of a foot ulcer. PMID- 26668683 TI - Cryoglobulinemic Glomerulonephritis as a Presentation of Atypical Post-Infectious Glomerulonephritis. AB - Post-infectious glomerulonephritis (PIGN) usually occurs within few days to weeks following an infection. Clinical presentation is variable, but in general, it is considered a benign entity with good prognosis. It rarely requires kidney biopsy to confirm the diagnosis. We present a case of a 55-year-old, previously healthy, male who presented for worsening shortness of breath, persistent cough, and right sided pleuritic chest pain. Initial workup revealed a right exudative effusion with empyema. Hospital course was complicated by acute kidney injury requiring renal replacement therapy with a peak creatinine of 10.2 mg/dL from a baseline of 1.18 mg/dL. On kidney biopsy, findings were compatible with a diagnosis of cryoglobulinemic glomerulonephritis or an atypical form of PIGN. While a wide variety of histopathological findings on renal biopsies have been described to complement the usual diffuse proliferative glomerulonephritis pattern, cryoglobulinemic features with negative cryoglobulin have never been reported. Our case is unique not only by having an atypical histological presentation but also by meeting the criteria of atypical PIGN with persistent hypertension and microscopic hematuria. PMID- 26668684 TI - Goodpasture's Disease: An Uncommon Disease With an Atypical Clinical Course. AB - Goodpasture's disease is an uncommon composite of features including renal failure with pulmonary hemorrhage secondary to an autoimmune response that specifically targets these organ systems. We present a case of particular interest in regards to atypical presentation, and the uncommon treatment that the patient underwent. A 65-year-old Afghani female arrived with complaints of nausea, vomiting, loss of appetite, malaise, decreased urine output, exertional dyspnea, and cough. The patient presented initially with renal failure and unexpectedly developed respiratory failure after hemodialysis. Initial CT of thorax revealed diffuse bilateral pulmonary edema. Subsequently, the patient received a bronchoscopy demonstrating alveolar hemorrhage, which highlights a clinician's need to maintain a differential and reassess patients. Anti-GBM antibody in the serum was detected and the renal biopsy revealed evidence of the antibody on immunofluorescence. In regards to management, the patient could only be treated with plasmapheresis as she had contraindication to initiation of immunosuppression, after which she showed significant clinical improvement. We would like to highlight the benefit of plasmapheresis without concomitant immunosuppression and recommend such an approach to be considered in similar clinical scenarios, where contraindication for immunosuppressant therapy exists. PMID- 26668685 TI - Newly Emerging Feeding Difficulties in a 33-Year-Old Adult With CHARGE Syndrome. AB - Feeding and swallowing difficulties are common among individuals with CHARGE syndrome. Many children require gastrostomy tube feeding in their early years and often undergo a delay in feeding and oral-motor skill development. There is little information available on adults with CHARGE syndrome, and the feeding difficulties they face. The present case describes newly emerging mouth over stuffing feeding behaviors and feeding difficulties in a 33-year-old adult with CHARGE syndrome who had not undergone feeding therapy since childhood. PMID- 26668686 TI - Cocaine-Induced Delayed Myocardial Infarction Complicated by Apical Thrombus. AB - It is well demonstrated in the literature that cocaine use has been well linked to the formation of various forms of acute and chronic cardiovascular problems including but not limited to acute coronary syndromes. However, cocaine has been commonly associated with coronary vasospasms and less commonly with myocardial infarction and the formation of atrial thrombus. Through this case presentation, we illustrate the findings of a 35-year-old gentleman with history of cocaine use presenting with acute coronary syndrome and complicated by thrombus formation. Furthermore, through this report, we illustrate in a patient with no other risk factors and at a young age, how chronic cocaine use or even a history of usage may result in complications even weeks after its consumption. PMID- 26668687 TI - Correction: Ioannis Dimitriou et al, Palmaris Longus Muscle's Prevalence in Different Nations and Interesting Anatomical Variations: Review of the Literature. AB - [This corrects the article DOI: 10.14740/jocmr2243w.]. PMID- 26668688 TI - Evaluation of the efficacy of bleach routinely used in health facilities against Mycobacterium tuberculosis isolates in Ethiopia. AB - INTRODUCTION: In Ethiopia, the most widely used disinfectant is 5% Hypochlorites. However, Ethiopian national health safety and infection prevention guideline recommendation on the use of bleach is not consistent and varying from 0.1%-4%. The purpose of this study was therefore to assess the effective time concentration relationship of sodium hypochlorite against Mycobacterium tuberculosis complex isolates in the absence of any organic load. METHODS: This experimental study was conducted in Bahir Dar Regional laboratory from February June 2013. Test suspensions of 1.5 X 10(8) CFU/ml prepared using normal saline containing 0.5% tween 80. From 5% stock, 0.1%, 0.5%, 1% and 2% bleach was prepared. A 1ml of test strain suspension and 1ml of bleach mixed and allowed to stand until the specified time achieved, neutralized by 48 ml phosphate buffer. 100ul from the diluted sediment were spread on two L-J mediums and incubated at 37 degrees C for 8 weeks. RESULTS: When 0. 1% bleach was used for 10 min, majority 11/20 of isolates showed 3 x 10(3) CFU/ml growth (ME = 4.4) which was inefficient. However, when the time increased, the log10 reduction was acceptable, ME >5 and it was effective. The bleach solution containing 0.5% and above was effective in all respective times. In this study, there is no difference observed in the tuberculocidal activity of bleach against resistant and sensitive strains. CONCLUSION: Our study showed that in the absence of any organic load, 0.1% bleaches over 15 min and 0.5% bleaches over 10 min was found to be tuberculocidal. PMID- 26668689 TI - [Moped accidents: injury mechanisms and clinicopathological aspects]. PMID- 26668690 TI - Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism. AB - Hepatocellular carcinoma (HCC) is the predominant subject of liver malignancies which arouse global concern. Advanced studies have found that long noncoding RNAs (lncRNAs) are differentially expressed in HCC and implicate they may play distinct roles in the pathogenesis and metastasis of HCC. However, the underlying mechanisms remain largely unclear. In this review, we summarized the functions and mechanisms of those known aberrantly expressed lncRNAs identified in human HCC tissues. We hope to enlighten more comprehensive researches on the detailed mechanisms of lncRNAs and their application in clinic, such as being used as diagnostic and prognostic biomarkers and the targets for potential therapy. Although studies on lncRNAs in HCC are still deficient, an improved understanding of the roles played by lncRNAs in HCC will lead to a much more effective utilization of those lncRNAs as novel candidates in early detection, diagnosis, prevention and treatment of HCC. PMID- 26668692 TI - Bile acid receptors and nonalcoholic fatty liver disease. AB - With the high prevalence of obesity, diabetes, and other features of the metabolic syndrome in United States, nonalcoholic fatty liver disease (NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis (NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor (TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH. PMID- 26668691 TI - Hepatitis C genotype 4: The past, present, and future. AB - Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother's HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in health-care centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the "most difficult (GT) to treat". Recently, the direct-acting antivirals (DAAs) with pan- genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients. PMID- 26668693 TI - Treating morbid obesity in cirrhosis: A quest of holy grail. AB - The problem of obesity is increasing worldwide in epidemic proportions; the situation is similarly becoming more common in patients with cirrhosis which negatively affect the prognosis of disease and also makes liver transplantation difficult especially in the living donor liver transplantation setting where low graft to recipient weight ratio negatively affects survival. Treatment of obesity is difficult in cirrhosis due to difficulty in implementation of lifestyle measures, limited data on safety of anti-obesity drugs and high risk of surgery. Currently approved anti-obesity drugs have limited data in patients with cirrhosis. Bariatric surgery remains an option in selected compensated cirrhotic patients. Endoscopic interventions for obesity are emerging and are quite promising in patients with cirrhosis as these are minimally invasive. In present review, we briefly discuss various modalities of weight reduction in obese patients and their applicability in patients with cirrhosis. PMID- 26668694 TI - Update on hepatitis C: Direct-acting antivirals. AB - Hepatitis C virus (HCV) was discovered 26 years ago. For decades, interferon based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals (DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon. PMID- 26668695 TI - Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis. AB - Transgenic mouse technology has enabled the investigation of the pathogenic effects, including those on development, immunological reactions and carcinogenesis, of viral genes directly in living organism in a real-time manner. Although viral hepatocarcinogenesis comprises multiple sequences of pathological events, that is, chronic necroinflammation and the subsequent regeneration of hepatocytes that induces the accumulation of genetic alterations and hepatocellular carcinoma (HCC), the direct action of viral proteins also play significant roles. The pathogenesis of hepatitis B virus X and hepatitis C virus (HCV) core genes has been extensively studied by virtue of their functions as a transactivator and a steatosis inducer, respectively. In particular, the mechanism of steatosis in HCV infection and its possible association with HCC has been well studied using HCV core gene transgenic mouse models. Although transgenic mouse models have remarkable advantages, they are intrinsically accompanied by some drawbacks when used to study human diseases. Therefore, the results obtained from transgenic mouse studies should be carefully interpreted in the context of whether or not they are well associated with human pathogenesis. PMID- 26668696 TI - Comparison of peg-interferon, ribavirin plus telaprevir vs simeprevir by propensity score matching. AB - AIM: To compare efficacy of telaprevir (TVR) and simeprevir (SMV) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV) while treating chronic hepatitis C (CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk (SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated. RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus (HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B (IL28B) genotype (rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds (n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28B genotype (rs8099917) as the only independent predictive factor of SVR12 in both groups. CONCLUSION: SVR12 rates were almost identical following propensity score matching. PMID- 26668698 TI - Medical Microbiology in Practice: past and current situations in Iran. PMID- 26668697 TI - Epidemiology of hepatitis C virus exposure in Egypt: Opportunities for prevention and evaluation. AB - AIM: To critically evaluate the current epidemiology data on exposures, rather than infection, to hepatitis C virus (HCV) transmission and recommend epidemiologic strategies to fill gaps. METHODS: Standard methods for identifying and evaluating relevant epidemiologic literature and available data were used. RESULTS: There is a large body of literature on the epidemiology of HCV transmission in Egypt that collectively identifies ongoing iatrogenic exposures as the major driver for HCV transmission due to short comings in infection control and standard procedures. Additional epidemiologic studies on HCV transmission that requires the participation of human subject is unwarranted. Alternatively, very little literature was found on the epidemiology of exposure to HCV, infection control, and safe injection practices. The information that is available on patterns of HCV exposure shows high frequencies of inadequate infection control, problems in sterilization in health care facilities, low rates of hand washing, untrained personnel, lack of stated policies in facilities, HCV contamination of instruments and very large injection frequencies with low but very significant syringe and needle reuse. There is an important need to increase the number, size, and diversity of epidemiologic studies on HCV exposures, patterns of risk factors for infection, infection control, and safe injection practices. In addition to health care facilities evaluation, relevant knowledge attitude and practice studies are recommended. CONCLUSION: Epidemiologic methods on HCV exposure can be used to characterize the magnitude of exposures to HCV infection, target interventions to reduce exposures, and provide the best method for evaluating interventions by demonstrating the reduction of exposure to HCV infection. PMID- 26668699 TI - Nosocomial Infections: Multicenter surveillance of antimicrobial resistance profile of Staphylococcus aureus and Gram negative rods isolated from blood and other sterile body fluids in Iran. AB - BACKGROUND AND OBJECTIVE: Antibiotic resistance is increasing, especially in healthcare-associated infections causing significant public health concerns worldwide. National information is required to make appropriate policies, update list of essential drugs for treatment, and evaluate the effects of intervention strategies. A nationwide surveillance of antimicrobial resistant bacteria in nosocomial infections was established in Iran in 2008, so that the data obtained through the surveillance would enable us to construct a database. MATERIALS AND METHODS: Seven major teaching hospitals in Shiraz, Tabriz, Sari, Mashhad, Sanandaj, Ahwaz and Isfahan participated in this study. A total of 858 strains isolated from blood and other sterile body fluids were tested. Identification at the species level was performed with conventional biochemical methods and the API system. Susceptibility tests were done using disk diffusion method. The methicillin-resistance in S. aureus (MRSA) was determined by the oxacillin agar screen plate and respective MIC values were assessed using the E-test strips. The confirmatory disk diffusion methods were applied for phenotypic identification of extended-spectrum beta- lactamase (ESBL) production for E. coli and K. pneumoniae, according to CLSI guidelines. RESULTS: Cultivation and re identification of the strains yielded 858 isolates, consisting of 224 S. aureus, 148 Klebsiella spp., 105 Serratia spp., 146 E. coli, 67 Acinetobacter spp., 38 Enterobacter spp., 95 Pseudomonas spp., 71 P.aeruginosa. 35 Stenotrophomonas sp., and 8 other organisms. MRSA was detected in 37.5% of the isolates. No vancomycin resistant or vancomycin-intermediate resistant S. aureus was detected. With the exception of Acinetobacter and Stenotrophomonas, 85% of the Gram-negative isolates were found to be susceptible in vitro to imipenem. Overall, about 61% of K. pneumoniae and 35% of E. coli isolates were ESBL producing. CONCLUSION: Multidrug resistant isolates of Gram-negative organisms and methicillin-resistant strains of S. aureus have been detected in many hospitals in this study. PMID- 26668700 TI - Genotyping of Haemophilus influenzae type b strains and their incidence in the clinical samples isolated from Iranian patients. AB - BACKGROUND AND OBJECTIVE: Haemophilus influenzae type b (Hib) is divided into two distinct genotypes, type I and type II, based on the structure of capsular polysaccharides. The capsulation locus of Haemophilus influenzae type b consists of three functionally distinct regions, designated regions 1 to 3. Region III contains hcsA and hcsB genes; however, notable sequence variation in this region can be used to recognize different Hib genotypes. The purpose of this study was to investigate the prevalence and genotype of the Hib strains isolated from patients with invasive disease in Iran. MATERIALS AND METHODS: In the present study, 8 pairs of primers were used for identification and serotyping of encapsulated Haemophilus influenzae strains, as well as confirmation of species identification. Additionally, in order to identify the capsular genotypes of Haemophilus influenzae type b (type I and II), two additional primer pairs were used to amplify the hcsA gene. RESULTS: Out of 50 isolates of H. influenzae, four were found to be type b. Interestingly, among these 4 Hib isolates, 2 strains belonged to the type-II category. CONCLUSION: Our study shows that the prevalence of both Hib types I and II seems to be high in Iran. PMID- 26668701 TI - Extended-spectrum beta-lactamase and carbapenemase production among burn and non burn clinical isolates of Klebsiella pneumoniae. AB - BACKGROUND AND OBJECTIVES: Klebsiella pneumoniae is an opportunistic pathogen responsible for up to 10% of nosocomial infections. The emergence and spread of multidrug resistant K. pneumoniae, mostly due to the production of extended spectrum beta-lactamases (ESBL) and carbapenemases, is often responsible for antibiotic treatment failure of these infections. We compared the antibiotic resistance profiles, ESBL and carbapenemase production as well as presence of KPC type genes in burn and non-burn clinical isolates of K. pneumoniae. MATERIALS AND METHODS: Fifty five clinical isolates were collected from Shahid Motahari (25 burn isolates) and Shariati (30 non-burn isolates) hospitals between August 2011 to January 2012. Antibiotic susceptibility was determined to 12 antibiotics using disc diffusion. The phenotypic confirmatory test (PCT) was used to screen for ESBL production. Carbapenemase activity was measured by the modified Hodge test (MHT) and KPC-type carbapenemases were further sought by PCR using specific primers. RESULTS: Both groups were highly resistant to cefotaxime and ceftazidime (>92%). Burn isolates were significantly more resistant to cefepime, amoxiclav, imipenem, meropenem, gentamicin and ciprofloxacin compared to the non-burn strains (p<0.05). No significant differences were observed in ESBL production between the two groups. Carbapenem resistance was only observed among the burn isolates (n=5, 9.1%). Five carbapenem-resistant isolates produced carbapenemases. However, none of the isolates harbored the KPC-type genes. CONCLUSION: Higher rates of drug resistance were observed in burn isolates of K. pneumoniae compared to the non-burn strains. Carbapenemase phenotype was only observed among the burn isolates but KPC-type gene was not detected. PMID- 26668702 TI - Synthesis, characterization and immunological properties of Escherichia coli 0157:H7 lipopolysaccharide- diphtheria toxoid conjugate vaccine. AB - BACKGROUND AND OBJECTIVE: Escherichia coli O157:H7, an emerging pathogen, causes severe enteritis and the extraintestinal complication of hemolytic-uremic syndrome. The goal of this study was to evaluate the conjugate of E. coli O157: H7 lipopolysaccharide (LPS) with diphtheria toxoid (DT) as a candidate vaccine in mice model. MATERIAL AND METHODS: LPS from E. coli O157:H7 was extracted by hot phenol method and then detoxified. Purified LPS was coupled to DT with adipic acid dihydrazide (ADH) as a spacer and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a linker. The coupling molar ratio of LPS to DT was 3:1. Clinical evaluation of E. coli O157:H7 LPS-DT conjugate was also performed. RESULTS: The conjugate was devoid of endotoxin activity and indicated 0.125 U/ml of D-LPS. Mice immunization with D-LPS DT conjugate elicited fourfold higher IgG antibody in comparison to D-LPS. Also, in vivo protection of mice with conjugate provided high protection against the LD50 of E. coli O157:H7, which indicated a good correlation with the IgG titer. CONCLUSION: Our results showed that the suggested vaccine composed of E. coli O157:H7 LPS and DT had a significant potential to protect against E. coli infections. PMID- 26668703 TI - Detection of lytA, pspC, and rrgA genes in Streptococcus pneumoniae isolated from healthy children. AB - BACKGROUND AND OBJECTIVES: Many surface proteins are implicated in nasopharyngeal colonization and pathogenesis of Streptococcus pneumoniae. Some of these factors are candidate antigens for protein based vaccines. New vaccine designs focus on the surface proteins (e. g., pspA and pspC) and also cytolysin, and pneumolysin. In this study, 3 key virulence genes, lytA, pspC, and rrgA, which encoded surface proteins, were detected among S. pneumoniae isolates. MATERIALS AND METHODS: A total of 260 nasopharyngeal swabs were collected from healthy children under 6 years old attending day care centers in Mashhad, Iran. Isolates of S. pneumoniae were confirmed by optochin susceptibility and colony appearance and also by PCR for cpsA gene. The presence of lytA, pspC, and rrgA genes were also detected by PCR. RESULTS: A total of 59 isolates were confirmed as S. pneumoniae. Among these isolates, 50 (84.74%), 19 (32.20%), and 2 (3.38%) were positive for lytA, rrgA, and pspC genes respectively. The presence of these genes among S.pneumoniae isolates were as follows: 1) rrgA, lytA, pspC (1 isolate), 2) rrgA, lytA(17isolates), 3) pspC (2 isolate), 4) lytA (50 isolates). CONCLUSION: cpsA gene was specific for detection of S. pneumoniae isolates which were colonized in nasopharynx. The lytA gene was the most frequent gene among the S. pneumoniae isolates, and combination of rrgA, lytA was the most observed pattern. Thus, it is important for future monitoring of vaccine formulation in our country. PMID- 26668705 TI - Genetic Characterization of Bacillus anthracis 17 JB strain. AB - BACKGROUND AND OBJECTIVES: Bacillus anthracis is one of the most homogenous bacteria ever described. Some level of diversity. Bacillus anthracis 17JB is a laboratory strain It is broadly used as a challenge strain in guinea pigs for potency test of anthrax vaccine. MATERIAL AND METHODS: This work describes genetic characterization of B. anthracis 17 JB strain using the SNPs and MLVA genotyping. RESULTS AND CONCLUSION: In SNPs typing, the originally French 17JB strain represented the A.Br. 008/009 subgroup. In Levy's genotyping method, 843, 451 and 864 bp long fragments were identified at AA03, AJ03 and AA07 loci, respectively. In the vaccine manufacturer perspective these findings are much valuable on their own account, but similar research is required to extend molecular knowledge of B. anthracis epidemiology in Persia. PMID- 26668704 TI - Detection of mecA and enterotoxin genes in Staphylococcus aureus isolates associated with bovine mastitis and characterization of Staphylococcal cassette chromosome mec (SCCmec) in MRSA strains. AB - BACKGROUND AND OBJECTIVES: Staphylococcus aureus is one of the main causatives of bovine mastitis. Resistance of some strains to methicillin, can complicate the treatment of its infections. On the other hand, enterotoxin production is also important. Therefore, the aim of our study was to investigate the methicillin resistance and enterotoxin production in S. aureus isolates caused bovine mastitis. MATERIALS AND METHODS: Four hundred and fifty milk samples were collected. After isolation of Staphylococcus aureus, MRSA strains were detected by cefoxitin disc diffusion and oxacillin agar screening methods. DNA was extracted by phenol - chloroform method and PCR was applied for mecA, sea and seb genes. SCCmec types of mecA gene were identified using multiplex-PCR. RESULTS: Fifty-four (12%) S. aureus were isolated. Out of these, 10 and 9 MRSA strains identified by cefoxitin disc diffusion and oxacillin agar screening methods, respectively. All 10 MRSA isolates identified by cefoxitin disc diffusion, were positive for mecA gene and all of them belonged to SCCmec type IV. The sea genes were detected in 19 isolates and only two isolates were positive for seb genes. One isolate possessed both sea and seb genes. CONCLUSION: Findings of this study indicated that results of cefoxitin disc diffusion test is in concordance with the PCR for mecA gene and has a higher sensitivity compared to oxacillin agar screening method. Finally, Our findings suggest that enterotoxin A is the dominant type. PMID- 26668706 TI - The antibacterial effect of sage extract (Salvia officinalis) mouthwash against Streptococcus mutans in dental plaque: a randomized clinical trial. AB - BACKGROUND AND OBJECTIVE: The aim of the study was to evaluate the clinical effects of a mouthwash containing Sage (Salvia officinalis) extracts on Streptococcus mutans (SM) causing dental plaque in school-aged children. MATERIAL AND METHODS: A double blind clinical trial study was conducted in a dormitory on 70 girls aged 11-14 years having the same socioeconomic and oral hygiene conditions. These students were randomly divided into 2 groups; the first group (N=35) using Sage mouthwash, and the second group (N=35) using placebo mouthwash without active any ingredients. At the baseline, plaque samples obtained from the buccal surfaces of teeth were sent to laboratory to achieve SM colony count. These tests were reevaluated after 21 days of using the mouthwashes. Statistical data analysis was performed using t-student tests with p<0.05 as the level of significance. RESULTS: Sage mouthwash significantly reduced the colony count (P=0.001). Average number of colonies in test group was 3900 per plaque sample at the baseline, and 300 after mouthwash application. In the control group, pre-test colony count was 4400 that was reduced to 4000; although this reduction wasn't significant. CONCLUSION: The Sage mouthwash effectively reduced the number of Streptococcus mutans in dental plaque. PMID- 26668707 TI - First time isolation of Photobacterium damselae subsp. damselae from Caranx sexfasciatus in Persian Gulf, Iran. AB - BACKGROUND AND OBJECTIVE: Photobacterium damselae subsp. damselae is a marine pathogenic bacterium which causes disease in marine animals and human. This bacterium mostly found in coastal shallow seawater. So, the aim of this study was isolation and characterization of Photobacterium damselae subsp. damselae from edible fish of Persian Gulf, Bandar Abbas. MATERIAL AND METHODS: Totally 100 fish from different species were evaluated and out of that 5 different types of fish with external symptoms including: Caranx sexfasciatus, Lethrinus olivaceus, Scomberoid tol, Auxis thazard and Liza macrolepis, were collected from Bandar Abbas local fish market in September 2013. The samples were cultured on Marin Agar 2216 and Thiosulfate Citrate Bile salts Sucrose Agar media and incubated at 25 degrees C for 48 hrs. Then the isolates were characterized using biochemical (API 20 NE system) and molecular techniques. In addition, antibiotic susceptibility, presence of poly beta hydroxy butyrate and hemolysis activity of isolates were evaluated. RESULTS AND CONCLUSION: Entirely, 30 Gram negative bacterial colonies were isolated from the selected fish. Among the isolates, two suspected colonies were identified as Photobacterium damselae from Caranx sexfasciatus with API 20NE biochemical test. This results confirmed by 16s rRNA sequencing method. Both isolates showed alpha hemolytic with existence of beta hydroxyl butyrate. Furthermore, the isolates were susceptible to ciprofloxacin, chloramphenicol and nalidixic acid. CONCLUSION: Overall, the study indicated first time isolation of this bacterium from one type of fish caught from Persian Gulf, which warns us to pay more attention to fishery in this geographical area. PMID- 26668708 TI - Characterizing Chain Processes in Visible Light Photoredox Catalysis. AB - The recognition that Ru(bpy)32+ andsimilar visible light absorbing transition metal complexes can be photocatalysts for a variety of synthetically useful organic reactions has resulted in a recent resurgence of interest in photoredox catalysis. However, many of the critical mechanistic aspects of this class of reactions remain poorly understood. In particular, the degree to which visible light photoredox reactions involve radical chain processes has been a point of some disagreement that has not been subjected to systematic analysis. We have now performed quantum yield measurements to demonstrate that threerepresentative, mechanistically distinct photoredox processes involve product-forming chain reactions. Moreover, we show that the combination of quantum yield and luminescence quenching experiments provides a rapid method to estimate the length of these chains. Together, these measurements constitute a robust, operationally facile strategy for characterizing chain processes in a wide range of visible light photoredox reactions. PMID- 26668709 TI - Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering. AB - Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. (14)C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering. PMID- 26668710 TI - Pulsed low-intensity ultrasound increases proliferation and extracelluar matrix production by human dermal fibroblasts in three-dimensional culture. AB - This study evaluated the effect of pulsed low-intensity ultrasound on cell proliferation, collagen production and glycosaminoglycan deposition by human dermal fibroblasts encapsulated in alginate. Hoechst 33258 assay for cell number, hydroxyproline assay for collagen content, dimethylmethylene blue assay for glycosaminoglycan content and scanning electron microscopy were performed on the encapsulated cells treated with pulsed low-intensity ultrasound and a control group that remained untreated. Pulsed low-intensity ultrasound showed a significant effect on cell proliferation and collagen deposition but no consistent pattern for glycosaminoglycan content. Alcian blue staining showed that glycosaminoglycans were deposited around the cells in both treated and control groups. These results suggest that pulsed low-intensity ultrasound alone shows a positive effect on cell proliferation and collagen deposition even without growth factor supplements. PMID- 26668711 TI - Titanium phosphate glass microcarriers induce enhanced osteogenic cell proliferation and human mesenchymal stem cell protein expression. AB - In this study, we have developed 50- to 100-um-sized titanium phosphate glass microcarriers (denoted as Ti5) that show enhanced proliferation of human mesenchymal stem cells and MG63 osteosarcoma cells, as well as enhanced human mesenchymal stem cell expression of bone differentiation markers, in comparison with commercially available glass microspheres at all time points. We also demonstrate that these microcarriers provide superior human mesenchymal stem cell proliferation with conventional Dulbecco's Modified Eagle medium than with a specially developed commercial stem cell medium. The microcarrier proliferative capacity is revealed by a 24-fold increase in MG63 cell numbers in spinner flask bioreactor studies performed over a 7-day period, versus only a 6-fold increase in control microspheres under the same conditions; the corresponding values of Ti5 and control microspheres under static culture are 8-fold and 7-fold, respectively. The capability of guided osteogenic differentiation is confirmed by ELISAs for bone morphogenetic protein-2 and osteopontin, which reveal significantly greater expression of these markers, especially osteopontin, by human mesenchymal stem cells on the Ti5 microspheres than on the control. Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces. Thus, the results demonstrate the suitability of the developed microspheres for use as microcarriers in bone tissue engineering applications. PMID- 26668712 TI - Safety and tolerability of 13-valent pneumococcal conjugate vaccine in healthy Chinese adults, children and infants. AB - OBJECTIVE: Pneumococcal disease is a global problem, including in China. The objective of this study was to provide safety data for single-dose 13-valent pneumococcal conjugate vaccine (PCV13) in Chinese subjects, needed to begin a phase III safety and immunogenicity study in Chinese infants. METHODS: Healthy Chinese adults (18-55 years), children (3-5 years), and infants (42-98 days) received a single dose of PCV13 in this open-label safety study. Local reactions and systemic events were collected for 7 days via an electronic diary; adverse events were recorded for 1 month after vaccination. RESULTS: All 72 (24 per group) screened subjects (58.3% males; mean +/- standard deviation [SD] age: 43.3 +/- 9.1 years [adults], 4.5 +/- 0.7 years [children], and 79.6 +/- 15.2 days [infants]) were enrolled, received vaccine, and completed the study. The most frequently reported local reactions per group were pain at the injection site (n = 23 adults [95.8%]), tenderness (n = 18 children [75%]), and swelling (n = 6 infants [25%]), none of which were severe. The mean duration of each local reaction was ?2.0 days in infants and ?2.4 days in children but in adults was 3.3 days for pain at the injection site and 9 days each for redness and swelling. Systemic events in adults were muscle pain (n = 5), fatigue (n = 3), and headache and joint pain (n = 1 each). One child and seven infants had disturbed sleep (increased or decreased). One adult and one child had mild fever (37.7-38.5 degrees C, as per China Food and Drug Administration guidelines). No subject used antipyretic medication. One adverse event (bronchopneumonia in an infant) was reported, which was serious, severe, and unrelated to vaccination. There were no deaths. CONCLUSIONS: A single dose of PCV13 was safe and well tolerated in healthy Chinese adults, children, and infants. This study provided the safety data to enable a phase III safety and immunogenicity registration trial in Chinese infants to proceed. PMID- 26668714 TI - Dexmedetomidine-associated fever in the intensive care unit. PMID- 26668715 TI - Pervasive satellite cell contribution to uninjured adult muscle fibers. AB - BACKGROUND: Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident muscle stem cells or satellite cells are required for muscle growth and repair, in uninjured muscle, these cells appear quiescent and metabolically inactive. To investigate the satellite cell contribution to myofibers in adult uninjured skeletal muscle, we labeled satellite cells by inducing a recombination of LSL-tdTomato in Pax7(CreER) mice and scoring tdTomato+ myofibers as an indicator of satellite cell fusion. RESULTS: Satellite cell fusion into myofibers plateaus postnatally between 8 and 12 weeks of age, reaching a steady state in hindlimb muscles, but in extra ocular or diaphragm muscles, satellite cell fusion is maintained at postnatal levels irrespective of the age assayed. Upon recombination and following a 2-week chase in 6-month-old mice, tdTomato-labeled satellite cells fused into myofibers as 20, 50, and 80 % of hindlimb, extra ocular, and diaphragm myofibers, respectively, were tdTomato+. Satellite cells contribute to uninjured myofibers either following a cell division or directly without an intervening cell division. CONCLUSIONS: The frequency of satellite cell fusion into the skeletal muscle fibers is greater than previously estimated, suggesting an important functional role for satellite cell fusion into adult myofibers and a requirement for active maintenance of satellite cell numbers in uninjured skeletal muscle. PMID- 26668713 TI - Routine deprescribing of chronic medications to combat polypharmacy. AB - The positive benefit-risk ratio of most drugs is decreasing in correlation to very old age, the extent of comorbidity, dementia, frailty and limited life expectancy (VOCODFLEX). First, we review the extent of inappropriate medication use and polypharmacy (IMUP) globally and highlight its negative medical, nursing, social and economic consequences. Second, we expose the main clinical/practical and perceptual obstacles that combine to create the negative vicious circle that eventually makes us feel frustrated and hopeless in treating VOCODFLEX in general, and in our 'war against IMUP' in particular. Third, we summarize the main international approaches/methods suggested and tried in different countries in an attempt to improve the ominous clinical and economic outcomes of IMUP; these include a variety of clinical, pharmacological, computer-assisted and educational programs. Lastly, we suggest a new comprehensive perception for providing good medical practice to VOCODFLEX in the 21st century. This includes new principles for research, education and clinical practice guidelines completely different from the 'single disease model' research and clinical rules we were raised upon and somehow 'fanatically' adopted in the 20th century. This new perception, based on palliative, geriatric and ethical principle, may provide fresh tools for treating VOCODFLEX in general and reducing IMUP in particular. PMID- 26668716 TI - Expression profiling and functional analysis of Toll-like receptors in primary healthy human nasal epithelial cells shows no correlation and a refractory LPS response. AB - BACKGROUND: Innate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses. Here we determine expression level variations and functionality of TLRs in nasal epithelial cells from healthy donors. METHODS: Expression levels of the different TLRs on primary nasal epithelial cells from healthy donors derived from inferior turbinates was determined by RT-PCR. Functionality of the TLRs was determined by stimulation with the respective ligand and evaluation of released mediators by Luminex ELISA. RESULTS: Primary nasal epithelial cells express different levels of TLR1-6 and TLR9. We were unable to detect mRNA of TLR7, TLR8 and TLR10. Stimulation with Poly(I:C) resulted in a significant increased secretion of IL-4, IL-6, RANTES, IP-10, MIP-1beta, VEGF, FGF, IL-1RA, IL-2R and G-CSF. Stimulation with PGN only resulted in significant increased production of IL-6, VEGF and IL-1RA. Although the expression of TLR4 and co stimulatory molecules could be confirmed, primary nasal epithelial cells appeared to be unresponsive to stimulation with LPS. Furthermore, we observed huge individual differences in TLR agonist-induced mediator release, which did not correlate with the respective expression of TLRs. CONCLUSION: Our data suggest that nasal epithelium seems to have developed a delicate system of discrimination and recognition of microbial patterns. Hypo-responsiveness to LPS could provide a mechanism to dampen the inflammatory response in the nasal mucosa in order to avoid a chronic inflammatory response. Individual, differential expression of TLRs on epithelial cells and functionality in terms of released mediators might be a crucial factor in explaining why some people develop allergies to common inhaled antigens, and others do not. PMID- 26668717 TI - Release from belowground enemies and shifts in root traits as interrelated drivers of alien plant invasion success: a hypothesis. AB - Our understanding of the interrelated mechanisms driving plant invasions, such as the interplay between enemy release and resource-acquisition traits, is biased by an aboveground perspective. To address this bias, I hypothesize that plant release from belowground enemies (especially fungal pathogens) will give invasive plant species a fitness advantage in the alien range, via shifts in root traits (e.g., increased specific root length and branching intensity) that increase resource uptake and competitive ability compared to native species in the alien range, and compared to plants of the invader in its native range. Such root-trait changes could be ecological or evolutionary in nature. I explain how shifts in root traits could occur as a consequence of enemy release and contribute to invasion success of alien plants, and how they could be interrelated with other potential belowground drivers of invasion success (allelopathy, mutualist enhancement). Finally, I outline the approaches that could be taken to test whether belowground enemy release results in increased competitive ability and nutrient uptake by invasive alien plants, via changes in root traits in the alien range. PMID- 26668718 TI - Symmetry and range limits in importance indices. AB - Recently, Mingo has analyzed the properties of I imp, an importance index, and demonstrated that its range is not symmetrical. While agreeing with this comment, we believe that more light needs to be shed on the issue of symmetry in relation to such indices. Importance indices are calculated using three values: performance of the organism in the absence and in the presence of neighbors and maximum performance of the organism in ideal conditions. Because of this structure, importance indices can hardly ever achieve symmetry along the whole range of potential performances. We discuss the limitation of the symmetry range for different symmetry types and for both additive and multiplicative indices. We conclude that importance indices, as other interactions indices, are practical tools for interpreting ecological outcomes, especially while comparing between studies. Nevertheless, the current structure of importance indices prevents symmetry along their whole range. While the lack of "perfect" symmetry may call for the development of more sophisticated importance metrics, the current indices are still helpful for the understanding of biological systems and should not be discarded before better alternatives are well established. To prevent potential confusion, we suggest that ecologists present the relevant index symmetry range in addition to their results, thus minimizing the probability of misinterpretation. PMID- 26668719 TI - Risk assessment based on indirect predation cues: revisiting fine-grained variation. AB - To adaptively express inducible defenses, prey must gauge risk based on indirect cues of predation. However, the information contained in indirect cues that enable prey to fine-tune their phenotypes to variation in risk is still unclear. In aquatic systems, research has focused on cue concentration as the key variable driving threat-sensitive responses to risk. However, while risk is measured as individuals killed per time, cue concentration may vary with either the number or biomass killed. Alternatively, fine-grained variation in cue, that is, frequency of cue pulses irrespective of concentration, may provide a more reliable signal of risk. Here, we present results from laboratory experiments that examine the relationship between red-eyed treefrog tadpole growth and total cue, cue per pulse, and cue pulse frequency. We also reanalyze an earlier study that examined the effect of fine-grained variation in predator cues on wood frog tadpole growth. Both studies show growth declines with increasing cue pulse frequency, even though individual pulses in high-frequency treatments contained very little cue. This result suggests that counter to earlier conclusions, tadpoles are using fine-grained variation in cue arising from the number of predation events to assess and respond to predation risk, as predicted by consumer-resource theory. PMID- 26668720 TI - Extensive mitochondrial heteroplasmy in hybrid water frog (Pelophylax spp.) populations from Southeast Europe. AB - Water frogs of the genus Pelophylax (previous Rana) species have been much studied in Europe for their outstanding reproductive mechanism in which sympatric hybridization between genetically distinct parental species produces diverse genetic forms of viable hybrid animals. The most common hybrid is P. esculentus that carries the genomes of both parental species, P. ridibundus and P. lessonae, but usually transfers the whole genome of only one parent to its offsprings (hybridogenesis). The evolutionary cost of transfer of the intact genome and hence the hemiclonal reproduction is the depletion of heterozygosity in the hybrid populations. Pelophylax esculentus presents an excellent example of the long-term sustained hybridization and hemiclonal reproduction in which the effects of the low genetic diversity are balanced through the novel mutations and periodic recombinations. In this study, we analyzed the mitochondrial (mt) and microsatellites DNA variations in hybrid Pelophylax populations from southern parts of the Pannonian Basin and a north-south transect of the Balkan Peninsula, which are home for a variety of Pelophylax genetic lineages. The mtDNA haplotypes found in this study corresponded to P. ridibundus and P. epeiroticus of the Balkan - Anatolian lineage (ridibundus-bedriagae) and to P. lessonae and a divergent lessonae haplotype of the lessonae lineage. The mtDNA genomes showed considerable intraspecific variation and geographic differentiation. The Balkan wide distributed P. ridibundus was found in all studied populations and its nuclear genome, along with either the lessonae or the endemic epeiroticus genome, in all hybrids. An unexpected finding was that the hybrid populations were invariably heteroplasmic, that is, they contained the mtDNA of both parental species. We discussed the possibility that such extensive heteroplasmy is a result of hybridization and it comes from regular leakage of the paternal mtDNA from a sperm of one species that fertilizes eggs of another. In this case, the mechanisms that protect the egg from heterospecific fertilization and further from the presence of sperm mtDNA could become compromised due to their differences and divergence at both, mitochondrial and nuclear DNA. The heteroplasmy once retained in the fertilized egg could be transmitted by hybrid backcrossing to the progeny and maintained in a population over generations. The role of interspecies and heteroplasmic hybrid animals due to their genomic diversity and better fitness compare to the parental species might be of the special importance in adaptations to miscellaneous and isolated environments at the Balkan Peninsula. PMID- 26668721 TI - Snow vole (Chionomys nivalis Martins) affects the redistribution of soil organic matter and hormone-like activity in the alpine ecosystem: ecological implications. AB - In alpine environments, colonies of snow vole (Chionomys nivalis Martins) cause strong pedoturbation, which may affect humification process and soil organic matter (SOM) cycling, with repercussions on the hormone-like activity of organics. We investigated the effect of snow vole pedoturbation on the chemical and spectroscopic features of soil organic fractions, and the potential hormone like activity of humic and fulvic acids (HA, FA). The study site was located on the high-mountain environment of the Majella massif (central Italy). Pedoturbated and regular soils were morphologically described and characterized for pH and content of total organic carbon, total extractable carbon, HA, and FA. Both HA and FA were extracted and investigated using attenuated total reflectance/Fourier transform infrared (ATR/FTIR), nuclear magnetic resonance with high-resolution magic angle spinning (HRMAS-NMR), and (1)H-(13)C heteronuclear single quantum coherence (HSQC). HA and FA were also tested for their auxin-like and gibberellin like activities. Results provide evidences that bioturbated and regular soils contain a poorly decomposed SOM, but HA and FA with a well-defined molecular structure. The HA and FA from both bioturbated and regular soils show a hormone like activity with a different allocation along the soil profile. In the regular soil, the highest auxin-like activity was shown by HA and FA from Oe1 horizon, while gibberellin-like activity was expressed by FA from Oe2 horizon. Burrowing activity determines a redistribution of organics throughout the profile with a relatively high auxin-like activity in the FA from straw tunnel wall (STW) and gibberellin-like activity in the HA from vole feces (VF). The relative high presence of carboxylic acids, amides, proteins, and amino acids in the FA from STW and the aromatic moieties in the HA from VF put evidences for their different behavior. The fact that snow vole activity has modified the chemical and biological properties of SOM in these soils otherwise considered governed only by low temperature has important ecological implications such as the preservation of soil fertility and vegetal biodiversity. PMID- 26668722 TI - A novel marine mesocosm facility to study global warming, water quality, and ocean acidification. AB - We describe a completely randomizable flow-through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6* water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open-source hardware board (Arduino) that was adapted to control heaters and an innovative CO 2 injection system. This system reduced seawater pH up to -0.9 units and increased temperature up to +6 degrees C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40-day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations. PMID- 26668723 TI - Maternal response to environmental unpredictability. AB - Mothers are expected to use environmental cues to modify maternal investment to optimize their fitness. However, when the environment varies unpredictably, cues may not be an accurate proxy of future conditions. Under such circumstances, selection favors a diversifying maternal investment strategy. While there is evidence that the environment is becoming more uncertain, the extent to which mothers are able to respond to this unpredictability is generally unknown. In this study, we test the hypothesis that Daphnia magna increase the variance in maternal investment in response to unpredictable variation in temperature consistent with global change predictions. We detected significant variability across temperature treatments in brood size, neonate size at birth, and time between broods. The estimated variability within-brood size was higher (albeit not statistically significant) in mothers reared in unpredictable temperature conditions. We also detected a cross-generational effect with the temperature history of mothers modulating the phenotypic response of F1's. Notably, our results diverged from the prediction that increased variability poses a greater risk to organisms than changes in mean temperature. Increased unpredictability in temperature had negligible effects on fitness-correlated traits. Mothers in the unpredictable treatment, survived as long, and produced as many F1's during lifetime as those produced in the most fecund treatment. Further, increased unpredictability in temperature did not affect the probability of survival of F1's. Collectively, we provide evidence that daphnia respond effectively to thermal unpredictability. But rather than increasing the variance in maternal investment, daphnia respond to uncertainty by being a jack of all temperatures, master of none. Importantly, our study highlights the essential need to examine changes in variances rather than merely on means, when investigating maternal responses. PMID- 26668724 TI - Comparison of dwarf bamboos (Indocalamus sp.) leaf parameters to determine relationship between spatial density of plants and total leaf area per plant. AB - The relationship between spatial density and size of plants is an important topic in plant ecology. The self-thinning rule suggests a -3/2 power between average biomass and density or a -1/2 power between stand yield and density. However, the self-thinning rule based on total leaf area per plant and density of plants has been neglected presumably because of the lack of a method that can accurately estimate the total leaf area per plant. We aimed to find the relationship between spatial density of plants and total leaf area per plant. We also attempted to provide a novel model for accurately describing the leaf shape of bamboos. We proposed a simplified Gielis equation with only two parameters to describe the leaf shape of bamboos one model parameter represented the overall ratio of leaf width to leaf length. Using this method, we compared some leaf parameters (leaf shape, number of leaves per plant, ratio of total leaf weight to aboveground weight per plant, and total leaf area per plant) of four bamboo species of genus Indocalamus Nakai (I. pedalis (Keng) P.C. Keng, I. pumilus Q.H. Dai and C.F. Keng, I. barbatus McClure, and I. victorialis P.C. Keng). We also explored the possible correlation between spatial density and total leaf area per plant using log-linear regression. We found that the simplified Gielis equation fit the leaf shape of four bamboo species very well. Although all these four species belonged to the same genus, there were still significant differences in leaf shape. Significant differences also existed in leaf area per plant, ratio of leaf weight to aboveground weight per plant, and leaf length. In addition, we found that the total leaf area per plant decreased with increased spatial density. Therefore, we directly demonstrated the self-thinning rule to improve light interception. PMID- 26668725 TI - Fish attraction to artificial reefs not always harmful: a simulation study. AB - The debate on whether artificial reefs produce new fish or simply attract existing fish biomass continues due to the difficulty in distinguishing these processes, and there remains considerable doubt as to whether artificial reefs are a harmful form of habitat modification. The harm typically associated with attraction is that fish will be easier to harvest due to the existing biomass aggregating at a newly deployed reef. This outcome of fish attraction has not progressed past an anecdotal form, however, and is always perceived as a harmful process. We present a numerical model that simulates the effect that a redistributed fish biomass, due to an artificial reef, has on fishing catch per unit effort (CPUE). This model can be used to identify the scenarios (in terms of reef, fish, and harvest characteristics) that pose the most risk of exploitation due to fish attraction. The properties of this model were compared to the long standing predictions by Bohnsack (1989) on the factors that increase the risk or the harm of attraction. Simulations revealed that attraction is not always harmful because it does not always increase maximum fish density. Rather, attraction sometimes disperses existing fish biomass making them harder to catch. Some attraction can be ideal, with CPUE lowest when attraction leads to an equal distribution of biomass between natural and artificial reefs. Simulations also showed that the outcomes from attraction depend on the characteristics of the target fish species, such that transient or pelagic species are often at more risk of harmful attraction than resident species. Our findings generally agree with Bohnsack's predictions, although we recommend distinguishing "mobility" and "fidelity" when identifying species most at risk from attraction, as these traits had great influence on patterns of harvest of attracted fish biomass. PMID- 26668726 TI - Body size but not warning signal luminance influences predation risk in recently metamorphosed poison frogs. AB - During early development, many aposematic species have bright and conspicuous warning appearance, but have yet to acquire chemical defenses, a phenotypic state which presumably makes them vulnerable to predation. Body size and signal luminance in particular are known to be sensitive to variation in early nutrition. However, the relative importance of these traits as determinants of predation risk in juveniles is not known. To address this question, we utilized computer-assisted design (CAD) and information on putative predator visual sensitivities to produce artificial models of postmetamorphic froglets that varied in terms of body size and signal luminance. We then deployed the artificial models in the field and measured rates of attack by birds and unknown predators. Our results indicate that body size was a significant predictor of artificial prey survival. Rates of attack by bird predators were significantly higher on smaller models. However, predation by birds did not differ between artificial models of varying signal luminance. This suggests that at the completion of metamorphosis, smaller froglets may be at a selective disadvantage, potentially because predators can discern they have relatively low levels of chemical defense compared to larger froglets. There is likely to be a premium on efficient foraging, giving rise to rapid growth and the acquisition of toxins from dietary sources in juvenile poison frogs. PMID- 26668727 TI - Effect of Yangtze River on population genetic structure of the relict plant Parrotia subaequalis in eastern China. AB - Parrotia subaequalis (Hamamelidaceae) is a Tertiary relic species endemic in eastern China. We used inter-simple sequence repeat (ISSR) markers to access genetic diversity and population genetic structure in natural five populations of P. subaequalis. The levels of genetic diversity were higher at species level (H = 0.2031) but lower at population level (H = 0.1096). The higher genetic diversity at species levels might be attributed to the accumulation of distinctive genotypes which adapted to the different habitats after Quaternary glaciations. Meanwhile, founder effects on the early stage, and subsequent bottleneck of population regeneration due to its biological characteristics, environmental features, and human activities, seemed to explain the low population levels of genetic diversity. The hierarchical AMOVA revealed high levels (42.60%) of among population genetic differentiation, which was in congruence with the high levels of Nei's genetic differentiation index (G ST = 0.4629) and limited gene flow (N m = 0.5801) among the studied populations. Mantel test showed a significant isolation-by-distance, indicating that geographic isolation has a significant effect on genetic structure in this species. Unweighted pair-group method with arithmetic average clustering, PCoA, and Bayesian analyses uniformly recovered groups that matched the geographical distribution of this species. In particular, our results suggest that Yangtze River has served as a natural barrier to gene flow between populations occurred on both riversides. Concerning the management of P. subaequalis, the high genetic differentiation among populations indicates that preserving all five natural populations in situ and collecting enough individuals from these populations for ex situ conservation are necessary. PMID- 26668728 TI - Evidence of niche shift and global invasion potential of the Tawny Crazy ant, Nylanderia fulva. AB - Analysis of an invasive species' niche shift between native and introduced ranges, along with potential distribution maps, can provide valuable information about its invasive potential. The tawny crazy ant, Nylanderia fulva, is a rapidly emerging and economically important invasive species in the southern United States. It is originally from east-central South America and has also invaded Colombia and the Caribbean Islands. Our objectives were to generate a global potential distribution map for N. fulva, identify important climatic drivers associated with its current distribution, and test whether N. fulva's realized climatic niche has shifted across its invasive range. We used MaxEnt niche model to map the potential distribution of N. fulva using its native and invaded range occurrences and climatic variables. We used principal component analysis methods for investigating potential shifts in the realized climatic niche of N. fulva during invasion. We found strong evidence for a shift in the realized climatic niche of N. fulva across its invasive range. Our models predicted potentially suitable habitat for N. fulva in the United States and other parts of the world. Our analyses suggest that the majority of observed occurrences of N. fulva in the United States represent stabilizing populations. Mean diurnal range in temperature, degree days at >=10 degrees C, and precipitation of driest quarter were the most important variables associated with N. fulva distribution. The climatic niche expansion demonstrated in our study may suggest significant plasticity in the ability of N. fulva to survive in areas with diverse temperature ranges shown by its tolerance for environmental conditions in the southern United States, Caribbean Islands, and Colombia. The risk maps produced in this study can be useful in preventing N. fulva's future spread, and in managing and monitoring currently infested areas. PMID- 26668729 TI - Interpreting behaviors from accelerometry: a method combining simplicity and objectivity. AB - Quantifying the behavior of motile, free-ranging animals is difficult. The accelerometry technique offers a method for recording behaviors but interpretation of the data is not straightforward. To date, analysis of such data has either involved subjective, study-specific assignments of behavior to acceleration data or the use of complex analyses based on machine learning. Here, we present a method for automatically classifying acceleration data to represent discrete, coarse-scale behaviors. The method centers on examining the shape of histograms of basic metrics readily derived from acceleration data to objectively determine threshold values by which to separate behaviors. Through application of this method to data collected on two distinct species with greatly differing behavioral repertoires, kittiwakes, and humans, the accuracy of this approach is demonstrated to be very high, comparable to that reported for other automated approaches already published. The method presented offers an alternative to existing methods as it uses biologically grounded arguments to distinguish behaviors, it is objective in determining values by which to separate these behaviors, and it is simple to implement, thus making it potentially widely applicable. The R script coding the method is provided. PMID- 26668730 TI - Fine root dynamics in lodgepole pine and white spruce stands along productivity gradients in reclaimed oil sands sites. AB - Open-pit mining activities in the oil sands region of Alberta, Canada, create disturbed lands that, by law, must be reclaimed to a land capability equivalent to that existed before the disturbance. Re-establishment of forest cover will be affected by the production and turnover rate of fine roots. However, the relationship between fine root dynamics and tree growth has not been studied in reclaimed oil sands sites. Fine root properties (root length density, mean surface area, total root biomass, and rates of root production, turnover, and decomposition) were assessed from May to October 2011 and 2012 using sequential coring and ingrowth core methods in lodgepole pine (Pinus contorta Dougl.) and white spruce (Picea glauca (Moench.) Voss) stands. The pine and spruce stands were planted on peat mineral soil mix placed over tailings sand and overburden substrates, respectively, in reclaimed oil sands sites in Alberta. We selected stands that form a productivity gradient (low, medium, and high productivities) of each tree species based on differences in tree height and diameter at breast height (DBH) increments. In lodgepole pine stands, fine root length density and fine root production, and turnover rates were in the order of high > medium > low productivity sites and were positively correlated with tree height and DBH and negatively correlated with soil salinity (P < 0.05). In white spruce stands, fine root surface area was the only parameter that increased along the productivity gradient and was negatively correlated with soil compaction. In conclusion, fine root dynamics along the stand productivity gradients were closely linked to stand productivity and were affected by limiting soil properties related to the specific substrate used for reconstructing the reclaimed soil. Understanding the impact of soil properties on fine root dynamics and overall stand productivity will help improve land reclamation outcomes. PMID- 26668731 TI - Modeling directional spatio-temporal processes in island biogeography. AB - A key challenge in island biogeography is to quantity the role of dispersal in shaping biodiversity patterns among the islands of a given archipelago. Here, we propose such a framework. Dispersal within oceanic archipelagos may be conceptualized as a spatio-temporal process dependent on: (1) the spatial distribution of islands, because the probability of successful dispersal is inversely related to the spatial distance between islands and (2) the chronological sequence of island formation that determines the directional asymmetry of dispersal (hypothesized to be predominantly from older to younger islands). From these premises, directional network models may be constructed, representing putative connections among islands. These models may be translated to eigenfunctions in order to be incorporated into statistical analysis. The framework was tested with 12 datasets from the Hawaii, Azores, and Canaries. The explanatory power of directional network models for explaining species composition patterns, assessed by the Jaccard dissimilarity index, was compared with simpler time-isolation models. The amount of variation explained by the network models ranged from 5.5% (for Coleoptera in Hawaii) to 60.2% (for Pteridophytes in Canary Islands). In relation to the four studied taxa, the variation explained by network models was higher for Pteridophytes in the three archipelagos. By the contrary, small fractions of explained variation were observed for Coleoptera (5.5%) and Araneae (8.6%) in Hawaii. Time-isolation models were, in general, not statistical significant and explained less variation than the equivalent directional network models for all the datasets. Directional network models provide a way for evaluating the spatio-temporal signature of species dispersal. The method allows building scenarios against which hypotheses about dispersal within archipelagos may be tested. The new framework may help to uncover the pathways via which species have colonized the islands of a given archipelago and to understand the origins of insular biodiversity. PMID- 26668732 TI - Niche divergence builds the case for ecological speciation in skinks of the Plestiodon skiltonianus species complex. AB - Adaptation to different thermal environments has the potential to cause evolutionary changes that are sufficient to drive ecological speciation. Here, we examine whether climate-based niche divergence in lizards of the Plestiodon skiltonianus species complex is consistent with the outcomes of such a process. Previous work on this group shows that a mechanical sexual barrier has evolved between species that differ mainly in body size and that the barrier may be a by product of selection for increased body size in lineages that have invaded xeric environments; however, baseline information on niche divergence among members of the group is lacking. We quantified the climatic niche using mechanistic physiological and correlative niche models and then estimated niche differences among species using ordination techniques and tests of niche overlap and equivalency. Our results show that the thermal niches of size-divergent, reproductively isolated morphospecies are significantly differentiated and that precipitation may have been as important as temperature in causing increased shifts in body size in xeric habitats. While these findings alone do not demonstrate thermal adaptation or identify the cause of speciation, their integration with earlier genetic and behavioral studies provides a useful test of phenotype-environment associations that further support the case for ecological speciation in these lizards. PMID- 26668733 TI - Bioacoustics for species management: two case studies with a Hawaiian forest bird. AB - The management of animal endangered species requires detailed information on their distribution and abundance, which is often hard to obtain. When animals communicate using sounds, one option is to use automatic sound recorders to gather information on the species for long periods of time with low effort. One drawback of this method is that processing all the information manually requires large amounts of time and effort. Our objective was to create a relatively "user friendly" (i.e., that does not require big programming skills) automatic detection algorithm to improve our ability to get basic data from sound-emitting animal species. We illustrate our algorithm by showing two possible applications with the Hawai'i 'Amakihi, Hemignathus virens virens, a forest bird from the island of Hawai'i. We first characterized the 'Amakihi song using recordings from areas where the species is present in high densities. We used this information to train a classification algorithm, the support vector machine (SVM), in order to identify 'Amakihi songs from a series of potential songs. We then used our algorithm to detect the species in areas where its presence had not been previously confirmed. We also used the algorithm to compare the relative abundance of the species in different areas where management actions may be applied. The SVM had an accuracy of 86.5% in identifying 'Amakihi. We confirmed the presence of the 'Amakihi at the study area using the algorithm. We also found that the relative abundance of 'Amakihi changes among study areas, and this information can be used to assess where management strategies for the species should be better implemented. Our automatic song detection algorithm is effective, "user-friendly" and can be very useful for optimizing the management and conservation of those endangered animal species that communicate acoustically. PMID- 26668734 TI - Vervet monkeys use paths consistent with context-specific spatial movement heuristics. AB - Animal foraging routes are analogous to the computationally demanding "traveling salesman problem" (TSP), where individuals must find the shortest path among several locations before returning to the start. Humans approximate solutions to TSPs using simple heuristics or "rules of thumb," but our knowledge of how other animals solve multidestination routing problems is incomplete. Most nonhuman primate species have shown limited ability to route plan. However, captive vervets were shown to solve a TSP for six sites. These results were consistent with either planning three steps ahead or a risk-avoidance strategy. I investigated how wild vervet monkeys (Chlorocebus pygerythrus) solved a path problem with six, equally rewarding food sites; where site arrangement allowed assessment of whether vervets found the shortest route and/or used paths consistent with one of three simple heuristics to navigate. Single vervets took the shortest possible path in fewer than half of the trials, usually in ways consistent with the most efficient heuristic (the convex hull). When in competition, vervets' paths were consistent with different, more efficient heuristics dependent on their dominance rank (a cluster strategy for dominants and the nearest neighbor rule for subordinates). These results suggest that, like humans, vervets may solve multidestination routing problems by applying simple, adaptive, context-specific "rules of thumb." The heuristics that were consistent with vervet paths in this study are the same as some of those asserted to be used by humans. These spatial movement strategies may have common evolutionary roots and be part of a universal mental navigational toolkit. Alternatively, they may have emerged through convergent evolution as the optimal way to solve multidestination routing problems. PMID- 26668736 TI - Corrigendum. AB - [This corrects the article DOI: 10.1002/ece3.333.]. PMID- 26668735 TI - Elevated carbon dioxide is predicted to promote coexistence among competing species in a trait-based model. AB - Differential species responses to atmospheric CO 2 concentration (Ca) could lead to quantitative changes in competition among species and community composition, with flow-on effects for ecosystem function. However, there has been little theoretical analysis of how elevated Ca (eC a) will affect plant competition, or how composition of plant communities might change. Such theoretical analysis is needed for developing testable hypotheses to frame experimental research. Here, we investigated theoretically how plant competition might change under eC a by implementing two alternative competition theories, resource use theory and resource capture theory, in a plant carbon and nitrogen cycling model. The model makes several novel predictions for the impact of eC a on plant community composition. Using resource use theory, the model predicts that eC a is unlikely to change species dominance in competition, but is likely to increase coexistence among species. Using resource capture theory, the model predicts that eC a may increase community evenness. Collectively, both theories suggest that eC a will favor coexistence and hence that species diversity should increase with eC a. Our theoretical analysis leads to a novel hypothesis for the impact of eC a on plant community composition. This hypothesis has potential to help guide the design and interpretation of eC a experiments. PMID- 26668738 TI - Longstanding insulin dependent diabetics may not require insulin after the introduction of GLP-1 analogues. AB - Glucagon like peptide (GLP-1) analogues are a relatively novel medication developed primarily for the treatment of type 2 diabetes since 2005. Although GLP 1 analogues have been shown to be more effective in the first few years of diagnosis in type 2 diabetes, we report a case of a patient with longstanding insulin-dependent diabetes started on a GLP-1 analogue, liraglutide, who now has controlled blood sugars without the need of insulin. PMID- 26668737 TI - Association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia: a retrospective cohort study. AB - BACKGROUND: Methicillin-resistant S. aureus (MRSA) pneumonia is associated with poor clinical outcomes. This study examined the association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia. FINDINGS: This retrospective cohort study included 75 patients with MRSA pneumonia who were admitted to two large tertiary care medical centers during 2003-2010. Multivariable models were created using Cox proportional hazards regression and ordinal logistic regression to identify predictors of mortality or increased length of stay (LOS). None of the microbial characteristics (PFGE type, agr dysfunction, SCCmec type, and detection of PVL, ACME, and TSST-1) were significantly associated with 30-day mortality or post infection hospital length of stay, after adjusting for gender, age, previous hospital admission within 12 months, previous MRSA infection or colonization, positive influenza test, Charlson Comorbidity Index score, and treatment (linezolid or vancomycin). CONCLUSION: Large prospective studies are needed to examine the impact of microbial characteristics on the risk of death and other adverse outcomes among patients with MRSA pneumonia. PMID- 26668739 TI - Microbubbles shunting via a patent foramen ovale impair endothelial function. AB - OBJECTIVES: Exposure to intravascular microbubbles after diving and during medical procedures alters endothelial function. The aim of this study was to investigate whether a patent foramen ovale altered forearm endothelial function by facilitating microbubbles transfer. DESIGN: Patients attended on two separate visits, at least seven days apart receiving agitated saline or no active intervention in random order. On both days, flow-mediated dilatation of the brachial artery was measured using vascular ultrasound. On the intervention visit, agitated saline was injected and the passage of microbubbles into the arterial circulation was confirmed by echocardiography. Serial flow-mediated dilatation measurements were made after agitated saline and at the same time points after no intervention. SETTING: St Thomas' Hospital in London. PARTICIPANTS: Patients with a patent foramen ovale (PFO+n = 14, 9 male, mean +/- SD age 42.2 +/- 10.5 years) and patients without a patent foramen ovale (PFO- n = 10, 7 male, mean +/- SD age 49.4 +/- 18.4 years) were recruited. MAIN OUTCOME MEASURES: Change in brachial artery flow-mediated dilatation. RESULTS: In patent foramen ovale + patients, flow-mediated dilatation did not change significantly on the control day but after agitated saline reduced by 2.3 +/- 0.3%, 20 minutes after bubble injection (P < 0.005 vs. corresponding change in flow-mediated dilatation during control study). There was no significant change in flow mediated dilatation for patent foramen ovale- patients at either visit. CONCLUSION: These results suggest that the presence of a patent foramen ovale facilitated impairment of endothelial function acutely by the transfer of microbubbles into the arterial circulation. As a patent foramen ovale is a common condition, this may be relevant to microbubbles exposure in medical procedures and in decompression illness. PMID- 26668740 TI - Public health impact and cost-effectiveness of dairy products supplemented with vitamin D in prevention of osteoporotic fractures. AB - BACKGROUND: Dietary sources of calcium and vitamin D are recommended as a first line strategy in prevention of osteoporosis-related fractures but their public health and economic impact has never been studied. METHODS: We designed a population-based model to forecast the potential health outcomes and medical effectiveness of the daily administration of dairy supplements containing 800 IU of vitamin D and 1 g of calcium in cohorts of subjects, from both genders, aged 50, 60, 70 and 80 years. Annual costs of dairy products were tested at ?150, ?250 and ?350. RESULTS: In total, the daily intake of vitamin-D rich dairy products reduces by 30,376 and 16,105 events the number of osteoporotic fractures in women and men respectively and permits to gain 6605 and 6144 life-years, in women and men respectively. This intervention is cost-effective from 70 years on in the general population and from 60 years on in patients at increased risk of osteoporotic fractures. CONCLUSION: The recommendation to use dairy products as the preferred source of calcium and vitamin D in aging males and females is supported by public health and health economic analyses. PMID- 26668741 TI - Budd-Chiari syndrome. AB - Budd-Chiari syndrome (BCS) is a rare and potentially life-threatening disorder characterized by obstruction of the hepatic outflow tract at any level between the junction of the inferior vena cava with the right atrium and the small hepatic veins. In the West, BCS is a rare hepatic manifestation of one or more underlying prothrombotic risk factors. The most common underlying prothrombotic risk factor is a myeloproliferative disorder, although it is now recognized that almost half of patients have multiple underlying prothrombotic risk factors. Clinical manifestations can be diverse, making BCS a possible differential diagnosis of many acute and chronic liver diseases. The index of suspicion should be very low if there is a known underlying prothrombotic risk factor and new onset of liver disease. Doppler ultrasound is sufficient for confirming the diagnosis, although tomographic imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) is often necessary for further treatment and discussion with a multidisciplinary team. Anticoagulation is the cornerstone of the treatment. Despite the use of anticoagulation, the majority of patients need additional (more invasive) treatment strategies. Algorithms consisting of local angioplasty, TIPS and liver transplantation have been proposed, with treatment choice dictated by a lack of response to a less-invasive treatment regimen. The application of these treatment strategies allows for a five-year survival rate of 90%. In the long term the disease course of BCS can sometimes be complicated by recurrence, progression of the underlying myeloproliferative disorder, or development of post-transplant lymphoma in transplant patients. PMID- 26668742 TI - Measurement of the tumor invasion depth into the submucosa in early adenocarcinoma of the esophagus (pT1b): Can microns be the new standard for the endoscopist? PMID- 26668743 TI - Submucosal invasion and risk of lymph node invasion in early Barrett's cancer: potential impact of different classification systems on patient management. AB - BACKGROUND: Due to the high mortality and morbidity rates of esophagectomy, endoscopic mucosal resection (EMR) is increasingly used for the curative treatment of early low risk Barrett's adenocarcinoma. OBJECTIVE: This retrospective cohort study aimed to assess the prevalence of lymph node metastases (LNM) in submucosal (T1b) esophageal adenocarcinomas (EAC) in relation to the absolute depth of submucosal tumor invasion and demonstrate the efficacy of EMR for low risk (well and moderately differentiated without lymphovascular invasion) EAC with sm1 invasion (submucosal invasion <=500 um) according to the Paris classification. METHODS: The pathology reports of patients undergoing endoscopic resection and surgery from January 1994 until December 2013 at one center were reviewed and 54 patients with submucosal invasion were included. LNM were evaluated in surgical specimens and by follow up examinations in case of EMR. RESULTS: No LNM were observed in 10 patients with sm1 adenocarcinomas that underwent endoscopic resection. Three of them underwent supplementary endoscopic eradication therapy with a median follow up of 27 months for patients with sm1 tumors. In the surgical series two patients (29%) with sm1 invasion according to the pragmatic classification (subdivision of the submucosa into three equal thirds), staged as sm2-3 in the Paris classification, had LNM. The rate of LNM for surgical patients with low risk sm1 tumors was 10% according to the pragmatic classification and 0% according to Paris classification. CONCLUSION: Different classifications of the tumor invasion depth lead to different LNM risks and treatment strategies for sm1 adenocarcinomas. Patients with low risk sm1 adenocarcinomas appear to be suitable candidates for EMR. PMID- 26668744 TI - Efficacy and safety of laparo-endoscopic resections of colorectal neoplasia: A systematic review. AB - OBJECTIVE: The purpose of this review is to assess the efficacy and safety of laparo-endoscopic local resections for colorectal lesions not suitable for endoscopic resection. SUMMARY BACKGROUND DATA: The combined laparo-endoscopic approach has been proposed for large colorectal lesions unsuitable for endoscopic resection, in order to reduce morbidity of common laparoscopic resection. However, data on the efficacy and safety of laparo-endoscopic local resections are still controversial. METHODS: An Embase search of papers published during the period 1985-2014 was performed. Published studies that evaluated laparo endoscopic resections for colorectal lesions were assessed using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) recommendations by two authors. Forest plots on primary (per-lesion rate of further surgery, including surgery for complications and surgery for oncologic radical treatment) and secondary outcomes were produced based on fixed and random effects models. Heterogeneity was assessed using the I (2) statistic. Risk for within-study bias was ascertained with QUADAS (Quality Assessment of Diagnostic Accuracy Studies) system. RESULTS: A total of 11 studies provided data on 707 lesions treated with a combined laparo-endoscopic approach. A variety of techniques were reported. The overall per-lesion rate of further surgery was 9.5%, while per-lesion rate of further surgery for oncologic treatment was 7.9%, per-lesion rate of further surgery for complications treatment was 3.5%, incidence of adenocarcinoma was 10.5%, incidence of overall complications was 7.9%, incidence of conversion to open surgery 4.3% and incidence of recurrence was 5.4%. CONCLUSIONS: Despite laparo-endoscopic approach ensures limited invasiveness, it is affected by a consistent rate of complications and oncologic inadequacy that often requires further surgical treatment. PMID- 26668745 TI - Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease. AB - BACKGROUND: Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. OBJECTIVES: Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. METHODS: We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. RESULTS: Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. CONCLUSIONS: In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease. PMID- 26668746 TI - Adrenal insufficiency predicts early mortality in patients with cirrhosis. AB - BACKGROUND: Adrenal insufficiency (AI), also known as hepato-adrenal syndrome, is a well-known entity in cirrhotic patients. However, factors associated with AI and its effect on survival are still not clear. We determined the prevalence of AI in patients with cirrhosis who had no hemodynamic instability or any acute deterioration, and studied its influence on short-term survival. PATIENTS AND METHODS: In consecutive cirrhotic patients, presence of AI was determined either by total serum cortisol <18 ug/dl, 60 minutes after 250 ug synacthen injection, or when the delta-fraction (post-synacthen serum cortisol minus basal serum cortisol) was <9 ug/dl. RESULTS: A total of 120 patients were included in the study (median age 50 years (range 27-73), males 87%). The median CTP and MELD scores were 10 (range 6-13) and 20 (range 6-40). The etiology of cirrhosis was alcohol (51%), cryptogenic (28%), viral (19%) and autoimmune (2%). Sixty-nine patients (58%) had AI and the remaining 51 (42%) had normal adrenal function. Serum bilirubin was significantly higher (p < 0.05) in the AI group, and total cholesterol, HDL, LDL and hemoglobin were significantly lower (p < 0.05) in the AI group. CTP score, MELD score, and basal cortisol levels were not different between those with and without AI (p = NS). By 120 days of follow-up, 41 patients had died. Thus, the 120-day survival was 66%, and this was higher in patients without AI than in patients with AI (78% vs 56%; p = 0.019). On multivariate analysis absence of AI, low WBC and low CTP score independently predicted 120-day survival. CONCLUSIONS: AI is present in more than half of cirrhotic patients but does not parallel the severity scores of cirrhosis. Its presence predicts early mortality in these patients, and this prediction is independent of CTP or MELD scores. PMID- 26668747 TI - The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis. AB - BACKGROUND: In humans there are epidemiological data suggesting a protective effect of Helicobacter pylori (H. pylori) infection against the development of autoimmune diseases and in addition, there are laboratory data illustrating H. pylori's ability to induce immune tolerance and limit inflammatory responses. Thus, numerous observational studies have examined the association between H. pylori infection and inflammatory bowel disease (IBD) with various results. OBJECTIVE: We performed a meta-analysis of available studies to better define the association of H. pylori infection and IBD. METHODS: Medical literature searches for human studies were performed through September 2014, using suitable keywords. In each study the risk ratio (RR) of H. pylori infection in IBD patients vs controls was calculated and pooled estimates were obtained using fixed- or random effects models as appropriate. Heterogeneity between studies was evaluated using Cochran Q test and I(2) statistics, whereas the likelihood of publication bias was assessed by constructing funnel plots. RESULTS: Thirty-three studies were eligible for meta-analysis, including 4400 IBD patients and 4763 controls. Overall 26.5% of IBD patients were positive for H. pylori infection, compared to 44.7% of individuals in the control group. There was significant heterogeneity in the included studies (Q = 137.2, df (Q) =32, I(2) ( )= 77%, p < 0.001) and therefore the random-effects model of meta-analysis was used. The obtained pool RR estimation was 0.62 (95% confidence interval (CI) 0.55-0.71, test for overall effect Z = -7.04, p < 0.001). There was no evidence of publication bias. CONCLUSION: The results of this meta-analysis showed a significant negative association between H. pylori infection and IBD that supports a possible protective benefit of H. pylori infection against the development of IBD. PMID- 26668749 TI - Reflecting on a memorable UEG Week 2015.... PMID- 26668750 TI - UEG Week Barcelona 2015 Award Winners. PMID- 26668748 TI - Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography: A single-center prospective study in 45 patients. AB - BACKGROUND: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC). AIMS: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year. RESULTS: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred. CONCLUSIONS: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer. PMID- 26668751 TI - Clinical development of Ebola vaccines. AB - The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID- 26668753 TI - Cholera toxin B induced activation of murine macrophages exposed to a fixed bacterial immunogen. AB - OBJECTIVES: Previous studies have demonstrated that intranasal administration of inactivated (fixed) Francisella tularensis (iFt) live vaccine strain (LVS) in conjunction with the mucosal adjuvant, cholera toxin B (CTB), provides full protection against subsequent lethal challenge with Ft LVS and partial protection against the more virulent Ft SchuS4 strain. Understanding the mechanisms of CTB induced immune stimulation that confer protection against Ft will be valuable to the development of an effective vaccine against this highly virulent fatal pathogen. In this study, an in vitro system was utilized to further elucidate the immunologic adjuvant effect of CTB when administered with the fixed bacterial immunogen iFt. METHODS: The murine macrophage cell line (RAW264.7) was treated with combinations of iFt and CTB. The treated RAW264.7 cells and their supernatants were collected and assessed for cell surface marker expression and cytokine secretion. In addition, the ability of RAW264.7 cells to present bacterial antigens (iFt or LVS) to an Ft-specific T-cell hybridoma cell line, following exposure to CTB, was analyzed. RESULTS: We found that RAW264.7 cells responded to treatment with iFt + CTB by an increased secretion of the proinflammatory cytokines interleukin 6 and tumor necrosis factor alpha and upregulation of the surface expression of toll-like receptor 4 and the costimulatory molecules CD80 and CD86. Furthermore, the experimental vaccine treatment iFt + CTB enhanced the ability of macrophages to present iFt antigens to an FT-specific T-cell hybridoma cell line, although they failed to do so with LVS. CONCLUSION: The adjuvant CTB administered in conjunction with iFt showed evidence of enhancing an antigen-specific proinflammatory response in vitro. These observations allow us to define, in part, the mechanisms of immune activation conferred by mucosal administration of iFt + CTB against lethal F. tularensis challenge. PMID- 26668752 TI - Plant-based vaccines for animals and humans: recent advances in technology and clinical trials. AB - It has been about 30 years since the first plant engineering technology was established. Although the concept of plant-based pharmaceuticals or vaccines motivates us to develop practicable commercial products using plant engineering, there are some difficulties in reaching the final goal: to manufacture an approved product. At present, the only plant-made vaccine approved by the United States Department of Agriculture is a Newcastle disease vaccine for poultry that is produced in suspension-cultured tobacco cells. The progress toward commercialization of plant-based vaccines takes much effort and time, but several candidate vaccines for use in humans and animals are in clinical trials. This review discusses plant engineering technologies and regulations relevant to the development of plant-based vaccines and provides an overview of human and animal vaccines currently under clinical trials. PMID- 26668754 TI - Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer. AB - BACKGROUND: Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. PURPOSE: To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. MATERIAL AND METHODS: Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. RESULTS: KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. CONCLUSION: The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites. PMID- 26668755 TI - Self-resolving focal non-ossifying myositis: a poorly known clinical and imaging entity diagnosed with MRI. AB - BACKGROUND: Focal myositis is a rare benign inflammatory pseudotumor, presenting as a painful nodular mass within a muscle, and characterized by spontaneous resolution within weeks. PURPOSE: To assess the clinical and imaging findings of focal nodular myositis simulating a neoplasm at clinical examination, with no history of trauma. MATERIAL AND METHODS: This study describes the locations and appearance at ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) of this condition in a series of five patients. RESULTS: MRI and US displayed a solid intramuscular "tumor" and suggested a continuum between the proximal and distal muscle fibers that appeared thickened within the nodular lesion, a sign that has been reported in myositis ossificans. MRI showed edema in adjacent muscles and soft tissues, as well as intense enhancement of the mass. Intense vascular flows were seen at Doppler analysis. CT did not reveal the appearance of peripheral ossifications, ruling out the diagnosis of myositis ossificans. In some patients, the diagnosis of sarcoma had been suggested as possible by the radiologist. Imaging follow-up with MRI showed complete resolution of the masses over several weeks, thus avoiding a biopsy; no recurrence was observed at long-term follow-up (more than 24 months). CONCLUSION: This paper highlights MRI and US findings in focal non-ossifying myositis, and emphasizes the role of MRI in suggesting this diagnosis, leading to the careful follow-up of the lesion until its resolution, and ruling out more aggressive lesions. PMID- 26668756 TI - Non-contrast-enhanced hepatic MR arteriography with balanced steady-state free precession and time spatial labeling inversion pulse: optimization of the inversion time at 3 Tesla. AB - BACKGROUND: A 3 Tesla (3 T) magnetic resonance (MR) scanner is a promising tool for upper abdominal angiography. However, no report has focused on the contrast behavior of non-contrast-enhanced hepatic MR arteriography at 3 T. PURPOSE: To establish the optimal inversion time (TI) for favorable selective visualization of the hepatic arteries on non-contrast-enhanced MR arteriography with time spatial labeling inversion pulse (Time-SLIP) at 3 T. MATERIAL AND METHODS: Twenty five healthy volunteers were examined using respiratory-triggered three dimensional balanced steady-state free-precession combined with Time-SLIP. According to the difference in the TI, five image groups (A, B, C, D, and E, from 1200 to 2000 ms, increasing at 200-ms intervals) were performed and compared to detect the optimal TI for hepatic artery visualization. The relative Cv-l (vessel to-liver contrast) was quantified. For qualitative evaluation, the vessel visualization quality and order of the depicted hepatic artery branches were evaluated. RESULTS: In group C (TI of 1600 ms), the Cv-l showed the highest probably due to a favorable balance between the hepatic vessel signal and signal recovery of the surrounding tissue. Regarding qualitative assessment, in group C, the mean image quality score of all hepatic arteries and mean maximal visible order of the hepatic artery branches were the highest. However, there was no significant difference between these results. CONCLUSION: Non-contrast-enhanced hepatic MR arteriography with Time-SLIP at 3 T enabled the selective visualization of hepatic arteries at a TI of 1600 ms with an optimal balance between Cv-l and peripheral hepatic artery visualization. PMID- 26668757 TI - Venous pattern of polymicrogyria detected by susceptibility weighted imaging (SWI). AB - We report a case of a 9-year-old boy presenting with spastic-dystonic movement disorder of the right arm. MRI showed vast unilateral left-sided polymicrogyria (PMG) with perisylvian, temporal, frontal, and parietal location. Corresponding to the distinctly reduced gyration, the focal pattern of cortical veins in susceptibility weighted imaging (SWI) was absent due to missing sulcal depth. In contrast, adjacent regions with sufficient sulcal depth revealed a pattern with numerically increased and finer cortical veins. Therefore, with its atypical venous pattern SWI indicates an abnormal parenchymal anatomy and might be an additional helpful tool for diagnosing PMG. PMID- 26668758 TI - Middle East respiratory syndrome in the Republic of Korea: transparency and communication are key. PMID- 26668759 TI - Investigation of chikungunya fever outbreak in Laguna, Philippines, 2012. AB - BACKGROUND: In July 2012, the Philippines National Epidemiology Center received a report of a suspected chikungunya fever outbreak in San Pablo City, Laguna Province, the first chikungunya cases reported from the city since surveillance started in 2007. We conducted an outbreak investigation to identify risk factors associated with chikungunya. METHODS: A case was defined as any resident of Concepcion Village in San Pablo City who had fever of at least two days duration and either joint pains or rash between 23 June and 6 August 2012. Cases were ascertained by conducting house-to-house canvassing and medical records review. An unmatched case-control study was conducted and analysed using a multivariate logistic regression. An environmental investigation was conducted by observing water and sanitation practices, and 100 households were surveyed to determine House and Breteau Indices. Human serum samples were collected for confirmation for chikungunya IgM through enzyme-linked immunosorbent assay. RESULTS: There were 98 cases identified. Multivariate analysis revealed that having a chikungunya case in the household (adjusted odds ratio [aOR]: 6.2; 95% confidence interval [CI]: 3.0-12.9) and disposing of garbage haphazardly (aOR: 2.7; 95% CI: 1.4-5.4) were associated with illness. House and Breteau Indices were 27% and 28%, respectively. Fifty-eight of 84 (69%) serum samples were positive for chikungunya IgM. CONCLUSION: It was not surprising that having a chikungunya case in a household was associated with illness in this outbreak. However, haphazard garbage disposal is not an established risk factor for the disease, although this could be linked to increased breeding sites for mosquitoes. PMID- 26668760 TI - Contact tracing the first Middle East respiratory syndrome case in the Philippines, February 2015. AB - BACKGROUND: Middle East respiratory syndrome (MERS) is an illness caused by a coronavirus in which infected persons develop severe acute respiratory illness. A person can be infected through close contacts. This is an outbreak investigation report of the first confirmed MERS case in the Philippines and the subsequent contact tracing activities. METHODS: Review of patient records and interviews with health-care personnel were done. Patient and close contacts were tested for MERS-coronavirus (CoV) by real time-polymerase chain reaction. Close contacts were identified and categorized. All traced contacts were monitored daily for appearance of illness for 14 days starting from the date of last known exposure to the confirmed case. A standard log sheet was used for symptom monitoring. RESULTS: The case was a 31-year-old female who was a health-care worker in Saudi Arabia. She had mild acute respiratory illness five days before travelling to the Philippines. On 1 February, she travelled with her husband to the Philippines while she had a fever. On 2 February, she attended a health facility in the Philippines. On 8 February, respiratory samples were tested for MERS-CoV and yielded positive results. A total of 449 close contacts were identified, and 297 (66%) were traced. Of those traced, 15 developed respiratory symptoms. All of them tested negative for MERS. DISCUSSION: In this outbreak investigation, the participation of health-care personnel in conducting vigorous contact tracing may have reduced the risk of transmission. However, being overly cautious to include more contacts for the outbreak response should be further reconsidered. PMID- 26668761 TI - Availability of safe drinking-water: the answer to cholera outbreak? Nabua, Camarines Sur, Philippines, 2012. AB - BACKGROUND: In May 2012, there were increasing diarrhoea cases and deaths reported from Nabua, Camarines Sur to the Philippines event-based surveillance system. An investigation was conducted to identify risk factors and determine transmission dynamics. METHODS: A suspected case was defined as a resident of Nabua with at least three episodes of watery diarrhoea per day from 16 March to 22 June 2012. A confirmed case was defined as a suspected case positive for Vibrio cholerae. An environmental investigation was conducted and rectal swabs and water samples sent to the national reference laboratory for bacterial isolation. A 1:2 case-control study matching for age and sex was conducted. Data were analysed using Epi Info. RESULTS: There were 309 suspected cases with two deaths, and the most affected age group was children under five years (45%). Eight cases were positive for Vibrio cholerae Ogawa El Tor and one for Non-01. Water samples were positive for faecal coliforms and Aeromonas caviae. The case control study showed that cases had a higher odds than controls of using unchlorinated water sources (odds ratio [OR] = 3.6; 95% confidence interval [CI]:1.6-8.5) and having toilets located within 20 m of a septic tank (OR = 2.7; 95% CI: 1.4-5.3). In multivariate analysis, the only significant factor was drinking from piped water (OR = 0.21; 95% CI: 0.09-0.49). DISCUSSION: In this cholera outbreak, drinking-water from unchlorinated wells was a significant risk factor. Future cholera control efforts should include not just improving water and sanitation systems but also intensified behaviour change campaigns. PMID- 26668762 TI - Measles outbreak investigation in a remote area of Solomon Islands, 2014. AB - OBJECTIVE: To describe a measles outbreak and health service response in a remote location in Malaita, Solomon Islands. METHODS: Epidemiological review of cases who presented to the Atoifi Adventist Hospital (AAH) during the outbreak period from July to December 2014. Rumour surveillance was used to gather information on unreported cases. RESULTS: A total of 117 cases were reported to AAH. The incidence rate was 123 per 10 000 individuals. Fifty-six per cent (66/117) of cases were hospitalized. Children under 5 years had the highest number of cases (n = 41) with 10 cases below 6 months old. The age-specific incidence rate of children under 5 years was 278.5 per 10 000 individuals. Eighty-two per cent of reported cases were 18 years old or younger. Rumour surveillance revealed about three quarters of children in one area of the East Kwaio Mountains had suspected measles not reported to AAH. There were three unreported deaths from measles outside AAH. During the outbreak, a total of 2453 measles-rubella vaccines were given in the AAH catchment area. CONCLUSION: A high incidence rate was observed in children and young people aged 18 years or younger, reflecting low childhood vaccination coverage. More than 50% of cases required hospitalization due to disease severity and challenges of accessing health services. The rumour surveillance discovered many unreported cases in the mountain areas and a few deaths possibly linked to the outbreak. Improvement of registration methods and follow-up systems and setting up satellite clinics are planned to improve measles surveillance and vaccination coverage. PMID- 26668763 TI - Event-based surveillance in north-western Ethiopia: experience and lessons learnt in the field. AB - This study piloted an event-based surveillance system at the health centre (HC) level in Ethiopia. The system collects rumours in the community and registers them in rumour logbooks to record events of disease outbreaks and public health emergencies. Descriptive analysis was conducted on the events captured at the 59 study HCs in the Amhara Region in north-western Ethiopia between October 2013 and November 2014. A total of 126 rumours were registered at two thirds of the HCs during the study period. The average event reporting time was 3.8 days; response time of the HCs was 0.6 days, resulting in a total response time of 4.4 days. The most commonly reported rumours were measles-related (n = 90, 71%). These rumours followed a similar pattern of measles cases reported in the routine surveillance system. The largest proportion of rumours were reported by community members (n = 38, 36%) followed by health post workers (n = 36, 29%) who were normally informed by the community members about the rumours. This surveillance system was established along with an existing indicator-based surveillance system and was simple to implement. The implementation cost was minimal, requiring only printing and distribution of rumour logbooks to the HCs and brief orientations to focal persons. In countries where routine surveillance is still weak, an event-based surveillance system similar to this should be considered as a supplementary tool for disease monitoring. PMID- 26668764 TI - Risk factors of neonatal tetanus in Wenzhou, China: a case-control study. AB - INTRODUCTION: Neonatal tetanus is a major cause of neonatal mortality in many developing countries and remains a major public health problem. This study aimed to determine risk factors associated with neonatal tetanus in Wenzhou, China. METHODOLOGY: Medical records of neonatal tetanus cases from 17 hospitals over a 13-year period (2000-2012) were reviewed for potential risk factors. Controls were selected from neonates with diseases other than tetanus who were admitted to the same facility during the same period. The potential risk factors of the neonatal tetanus group were compared with the control group using univariate analysis and an unconditional logistic regression model. RESULTS: A total of 246 neonates with tetanus and 257 controls were included in this study. Univariate analysis showed that having untrained birth attendants, home delivery, an unsterile method of delivery and being a migrant to Wenzhou were significantly different between the two groups (P < 0.001). Logistic regression analysis revealed that the odds of having an untrained birth attendant, home delivery and an unsterile method of delivery were significantly higher in the tetanus group than the control group (odds ratio: 1371.0; 95% confidence interval: 206.0, 9123.5). CONCLUSION: This study identified that the main risks of neonatal tetanus in cases from Wenzhou were having an untrained birth attendant, home delivery and an unsterile method of delivery. Preventive measures directed to these risk factors may reduce the occurrence of neonatal tetanus in the studied area. PMID- 26668765 TI - Global Handwashing Day 2012: a qualitative content analysis of Chinese social media reaction to a health promotion event. AB - BACKGROUND: Global Handwashing Day (GHD) is a handwashing promotion campaign organized by the Global Public-Private Partnership of Handwashing with Soap. In China, it has been promoted by the Chinese public health authorities, international organizations and multinational corporations through various channels including social media such as Sina Weibo, the leading Chinese microblogging site similar to Twitter. The objective of this study is to qualitatively assess Chinese social media users' reactions to a health promotion campaign using Global Handwashing Day (GHD) 2012 as an example. METHODS: We conducted a qualitative content analysis of 552 Weibo posts generated on GHD 2012 by Weibo users with 1000 or more followers with the Chinese keyword for "handwashing." We categorized the Weibo posts into groups by keywords that frequently appeared in the data set. These groups were either exact reposts of an original post, or they conveyed similar information. RESULTS: We observed the interconnections between traditional media and social media in handwashing promotion. Social media were found to serve as amplifiers of contents provided by traditional media. We observed the contextualization of global hygiene messages in a unique national social media market in China. DISCUSSION: Our study showed that social media and traditional media are two interconnected arms of the GHD campaign in China. Our analysis demonstrated that public health campaigns in China can be evaluated using social media data. The themes and topics identified in this study will help public health practitioners evaluate future social media handwashing promotion campaigns. PMID- 26668766 TI - An assessment of measles vaccine effectiveness, Australia, 2006-2012. AB - OBJECTIVE: Vaccine effectiveness analysis serves as a critical evaluation for immunization programmes and vaccination coverage. It also contributes to maintaining public confidence with the vaccine providers. This study estimated measles vaccine effectiveness at the population level using Australian national notifications data between 2006 and 2012. METHODS: Notification data were obtained from the National Notifiable Diseases Surveillance System. Vaccination status was classified according to whether a case had received zero, one or two doses of measles-containing vaccine. Cases aged less than 1 year and those with unknown vaccination status were excluded. All children with disease onset between 1 January 2006 and 31 December 2012 who were born after 1996 were included. Cases were matched to controls extracted from the Australian Childhood Immunization Register according to date of birth and jurisdiction of residence. Vaccine effectiveness was estimated by conditional logistic regression. Sensitivity analyses were conducted to test data robustness. RESULTS: Vaccine effectiveness was estimated at 96.7% (95% confidence interval [CI]: 94.5-98.0%) for one dose and 99.7% (95% CI: 99.2-99.9%) for two doses of measles vaccine. For at least one dose, effectiveness was estimated at 98.7% (95% CI: 97.9-99.2%). Sensitivity analyses did not significantly alter the base estimates. DISCUSSION: Vaccine effectiveness estimates suggested that the measles vaccine was protective at the population level between 2006 and 2012. However, vaccination coverage gaps may have contributed to recent measles outbreaks and may represent a serious barrier for Australia to maintain measles elimination status. PMID- 26668768 TI - The epidemiology of tuberculosis in the Pacific, 2000 to 2013. AB - OBJECTIVE: Tuberculosis (TB) poses a significant public health challenge in the 22 Pacific island countries and territories. Using TB surveillance data and World Health Organization (WHO) estimates from 2000 to 2013, we summarize the epidemiology of TB in the Pacific. METHODS: This was a descriptive study of incident TB cases reported annually by Pacific island national TB programmes to WHO. We counted cases and calculated proportions and case notification rates per 100,000 population. We calculated the proportion of TB patients who completed TB treatment and summed estimates of national incidence, prevalence and mortality, provided by WHO, to produce regional incidence, prevalence and mortality rates per 100,000 population. RESULTS: Estimated TB incidence in the Pacific has remained high but stable from 2000 to 2013; estimated prevalence and mortality have fallen by 20% and 47%, respectively. The TB case notification rate increased by 58%, from 146 to 231 per 100,000 population in the same time period. In 2013, 24,145 TB cases were notified, most (94% or 22,657) were from Papua New Guinea. Kiribati had the highest TB case notification rate at 398 cases per 100,000 population. TB case notification rates were also high in Papua New Guinea, the Marshall Islands and Tuvalu (309, 283 and 182, respectively). DISCUSSION: TB in the Pacific is improving in some areas; however, high rates affect many countries and the estimated regional incidence rate is stable. To further reduce the burden of TB, a combination of dedicated public health and system-wide approaches are required along with poverty reduction and social protection initiatives. PMID- 26668767 TI - Prevalence of soil-transmitted helminths in remote villages in East Kwaio, Solomon Islands. AB - OBJECTIVE: Although soil-transmitted helminths (STH) are endemic in Solomon Islands, there are few recent reports on their prevalence. This study aimed to determine the prevalence of STH in residents of remote communities in Solomon Islands. METHODS: A cross-sectional convenience-sampled survey of residents of four adjacent villages in Malaita, Solomon Islands was performed in Atoifi and Na'au in April 2011 and in Abitona and Sifilo in April 2012. All residents older than one year were invited to participate, which involved providing a single sample of faeces examined using a modified Kato-Katz technique and completing a questionnaire that asked demographic and STH-related behaviour questions. RESULTS: The overall participation rate was 52.8%, with 402 participants comprising 49.8% males. Hookworm was the predominant STH with only a single case of trichuriasis found in Atoifi. The total prevalence of hookworm was 22.6% (95% confidence interval: 18.6-27.1); the prevalence of hookworm in Abitona, Na'au and Sifilo was 20.0%, 29.9% and 27.4%, respectively, whereas in Atoifi it was 2.3% (P < 0.001). Intensity was low in all villages. Although health behaviours differed significantly between Atoifi and the other three villages, the type of toilet used was the only significant association with hookworm. DISCUSSION: Residents of Atoifi have a relative freedom from STH compared to the other three villages. Rather than a region-wide morbidity control approach, a "one village at a time" approach aiming to eliminate STH and dealing with each village as a separate autonomous unit empowered to manage its own challenges may be a preferred option. PMID- 26668771 TI - Assessing the Prevalence of Traumatic Head Injury amongst Recreational Surfers in the United States. AB - Surfing is a popular recreational sport that carries a substantial risk of injury. Although head injuries are frequently documented in the surfing population, an in depth assessment of the prevalence of surfing-related head injury has not been reported. A web-based survey was conducted in May of 2015. Participants were asked a series of questions regarding surfing-related injuries and demographic characteristics. A total of 50 responses were obtained, of which 35 (70%) reported sustaining a head injury. The most common injury was laceration of the head/face (n=27), followed by concussion (n=13). Other injuries, such as skull fracture and broken nose, were also reported. Only 2 of the 50 participants reported wearing a protective helmet. Neurosurgical intervention was required in 2 instances. Increased emphasis on preventative measures by the medical community may reduce the future incidence of such injuries. Medical professionals should be aware of the most common forms of injury sustained by the surfing population in order to better recognize and treat these conditions. PMID- 26668769 TI - Sex matters - a preliminary analysis of Middle East respiratory syndrome in the Republic of Korea, 2015. PMID- 26668770 TI - Disparities in Infant Mortality Due to Congenital Anomalies on Guam. AB - In the 1970's and 1980's, there were large inter-village disparities in infant mortality due to congenital anomalies on Guam. A village-level analysis was conducted to determine if these disparities can be explained by behavioral (ie, median age of village females, village fertility ratio), structural (ie, population density, persons per household, single mother households per village, married females per village), and environmental (ie, living in a village where Agent Orange (AO) spraying was conducted) factors. Village-level data for live births and infant mortality due to congenital anomalies (1970-1989) was collected from Guam's Office of Vital Statistics. Data on median age of village females, village fertility ratio, population density, persons per household, single mother households, and married females were obtained from the 1980 US Census. Estimates of village-level AO use were provided through personal communications, and villages were dichotomized into AO and non-AO spray areas. Village location was classified by usual residence of the mother. Linear regression was used to determine associations between infant mortality due to congenital anomalies and the behavioral, structural, and environmental factors. The association between AO spray area and infant mortality due to congenital anomalies was statistically significant under univariable (B [95%CI] = 1.88 [0.64,3.11], P = .005) and multivariable conditions (B [95%CI] = 2.02 [0.08,3.96], P = .042). These results suggest that infants born to mothers whose usual residence was in an AO spray area on Guam are at an increased risk of mortality due to congenital anomalies. Further studies using individual-level data are needed to validate these results. PMID- 26668772 TI - Sociocultural Factors that Affect Chewing Behaviors among Betel Nut Chewers and Ex-Chewers on Guam. AB - Areca nut (betel nut) is chewed by an estimated 10% of the world's population which is equivalent to about 600 million people. It is classified as a Group 1 carcinogen by the World Health Organization (WHO) and has been linked to various types of oral cancer. Chewing areca predominates in South and South East Asia, East Africa, and the Western Pacific and has important social and cultural implications. The purpose of the pilot study was twofold: (1) to examine sociocultural factors that affect why people on Guam chew betel nut, their chewing behaviors, perceptions of risks, probability of changing behaviors, and methods that could be used to reduce use or quit; and (2) to pilot two surveys (one for chewers and one for ex-chewers) to be used in a larger study in the future. A mixed methods design was employed that included surveys pertaining to their status (chewer or ex-chewer) and in-depth interviews. A total of 30 adults participated in this pilot study: adult betel nut chewers (n = 15) and ex-chewers (n = 15). Chewing betel nut is a learned behavior, embedded within the culture, and is viewed as an important cultural identifier. Socially, chewing is viewed as positive. Chewers stated that they were not as aware of health issues; however, ex-chewers stated health reasons for quitting. PMID- 26668773 TI - Medical School Hotline: Liaison Committee on Medical Education Accreditation, Part III: Educational Program Content, Curriculum Management, and Student Assessment. PMID- 26668774 TI - Insights in Public Health: Newborn Screening Saves Babies Using Public/Private Partnerships. PMID- 26668776 TI - The role of L-type amino acid transporter 1 in human tumors. AB - L-type amino acid transporter 1 (LAT1) is an L-type amino acid transporter and transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine. LAT1 was found to be highly expressed especially in human cancer tissues, and up-regulated LAT1 can lead to dysfunction in human tumor cells. These findings suggest that LAT1 plays an important role in human tumors. This review provides an overview of the current understanding of LAT1 expression and its clinical significance and function in tumors. PMID- 26668778 TI - Prediction of prognosis of ALS: Importance of active denervation findings of the cervical-upper limb area and trunk area. AB - Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by serious muscle atrophy and weakness. The purpose of this study was to find prognostic factors in patients with mild ALS using application forms for the Specified Disease Treatment Research Program in Japan. We classified ALS as mild, moderate and severe. The subjects consisted of 363 patients with mild ALS who underwent needle electromyography at registration and were followed for more than one year. Time to progression to severe ALS and time to deterioration of activities of daily living such as speech dysfunction, upper limb dysfunction, and walking disability were used as outcomes. Cox proportional hazards model analysis was performed to identify prognostic factors. Of the patients with initially mild ALS, 38.3% (139/363) had progressed severe ALS at the last follow up. In multivariate analysis of time to progression to severe ALS, bulbar onset (hazard ratio [95% confidence interval]: 1.68 [1.13-2.49], p = 0.010), tongue atrophy (1.69 [1.14-2.51], p = 0.009), dyspnea (1.57 [1.02-2.41], p = 0.042) and active denervation findings (ADFs) of the cervical-upper limb area (1.81 [1.25 2.63], p = 0.002) emerged as prognostic factors. Furthermore ADFs in the trunk area were prognostic factors for upper limb dysfunction and walking disability (1.72 [1.05-2.81], p = 0.031, and 1.97 [1.09-3.59], p = 0.026). In conclusion ADFs of the cervical-upper limb area and trunk area were prognostic factors in ALS patients. PMID- 26668779 TI - Multiplex cytokine analysis of Werner syndrome. AB - We reported a minor inflammation-driven ageing (inflammageing) assessed by highly sensitive CRP (hsCRP) in normal individuals and patients with Werner syndrome (WS), followed by an ageing associated Th2-biased cytokine change in normal ageing in the previous papers. To further study the association of hsCRP and 26 cytokines/chemokines in 35 WS patients, a multiple cytokine array system was used in the same serum samples as were examined for hsCRP. The serum levels of Th2 cytokines (IL-4, IL-6, IL-10, and GM-CSF), Th1 products (IL-2, TNFalpha, IL-12, and IFNgamma) and monocyte/macrophage products (MCP-1, basic FGF and G-CSF) in WS were significantly elevated compared with normal ageing. Elevated hsCRP level in WS was significantly correlated with IL-6, IL-12 and VEGF levels, if age and sex were taken into account. A pro-inflammatory cytokine/chemokine circuit-stimulated immunological shift to Th2 in WS was similar to normal ageing. These cytokine/chemokine changes may induce a systemic chronic inflammation monitored by hsCRP, though these immunological changes in WS were more complicated than normal ageing, possibly due to the WS-specific chronic inflammation such as skin ulcer, diabetes mellitus and central obesity with visceral fat deposition. Further study may warrant the pathophysiology of Th2 shift and Th2-biased inflammageing in normal ageing and WS. PMID- 26668777 TI - Sarcoidosis and the heart: A review of the literature. AB - Sarcoidosis is a chronic multisystem disorder without any defined etiology. Cardiac sarcoidosis (CS) is detected in 2-7% of patients with sarcoidosis and more than 20% of the cases of sarcoidosis are clinically silent. Cardiac involvement in systemic sarcoidosis (SS) and isolated cardiac sarcoidosis (iCS) are associated with arrhythmia and severe heart failure (HF) and have a poor prognosis. Early diagnosis of CS and prompt initiation of corticosteroid therapy with or without other immunosuppressants is crucial. Electrocardiography, Holter monitoring, and Doppler echocardiography with speckle tracking imaging can serve as the initial steps to diagnosis of CS. Cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET) are promising techniques for both diagnosis and follow-up of CS. This review discusses the main aspects of cardiac involvement in sarcoidosis. PMID- 26668780 TI - Identification of a male with fragile X syndrome through newborn screening. AB - A pilot newborn screening (NBS) study for fragile X syndrome was recently conducted at the University of California, Davis Medical Center. The screening study identified a case of a male with the full mutation completely methylated and no detectable expression of the fragile X mental retardation-1 (FMR1) gene. The patient was initially seen in clinic at the MIND Institute, for medical follow-up and a genetic counseling session at the chronological age of 3 months. Since then, he has been seen in clinic every six months for follow up, medical examination and developmental assessments. Longitudinally administered developmental testing of the infant has revealed persistent delays in development, consistent with fragile X syndrome. Cascade testing revealed that the patient's mother and two siblings also have the full mutation. The patient has been receiving speech and language therapy, combined with physical and occupational therapies on a weekly basis since the age of one year. He is currently being treated with 2.5 mg of sertraline, which has been demonstrated to be helpful for improving language in young children with the syndrome. PMID- 26668781 TI - An isolated single L-II type coronary artery anomaly: A rare coronary anomaly. AB - The incidence of congenital artery anomalies is 0.2-1.4%, and most are benign. Single coronary artery (SCA) anomalies are very rare. The right coronary artery (RCA) originating from the left coronary system is one such SCA anomaly, and the risk of sudden cardiac death (SCD) increases if it courses between the pulmonary artery and aorta and coexists with other congenital heart diseases. Additionally, coursing of the RCA between the great vessels increases the risk of atherosclerosis. We herein present the case of a 57 year-old man who was admitted to our cardiology outpatient clinic and diagnosed with an SCA anomaly in which the RCA arose from the left main coronary artery (LMCA) and coursed between the pulmonary artery and aorta. However a critical stenosis was not detected in imaging techniques, and myocardial perfusion scintigraphic evidence of ischaemia was found in a small area. Therefore, he was managed with conservative medical therapy. PMID- 26668782 TI - Azathioprine-induced atrial fibrillation. AB - Azathioprine, a purine analogue that competitively inhibits the biosynthesis of purine nucleotides, is used in a wide range of conditions. Although its side effects are well known, cardiac side effects like paroxysmal atrial fibrillation (AF) are based on only a few case reports. We describe here the case of a 55-year old woman with primary biliary cirrhosis who presented a first-detected, symptomatic AF 2 h after azathioprine therapy which resolved after discontinuation of the drug with no predisposing factors for supraventricular arrhythmias (systemic hypertension, diabetes or coronary artery disease). The temporal coincidence of atrial fibrillation and azathioprine intake and disappearance of the AF episode after discontinuation of therapy allows us to suggest an intrinsic pro-arrhythmic effect of azathioprine. Therefore, physicians should be aware of this problem when this drug is administered. PMID- 26668783 TI - Infantile systemic hyalinosis in identical twins. AB - Infantile systemic hyalinosis (ISH) is a rare disorder belonging to the heterogeneous group of genetic fibromatoses. It is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues caused by mutations in the anthrax toxin receptor 2 gene - ANTXR2. It presents hyperpigmented skin over bony prominences. Characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, spine and elbows, with progressive joint contractures, osteopenia, skin abnormalities and chronic severe pain. The present case reports the occurrence of infantile systemic hyalinosis in twin brothers five months of age who had come for early intervention for joint contractures representing characteristic brownish patches over bony prominences. ISH cases reported until this date have been less than 20 and the present case is unique in nature since this is the first time ISH is reported in twins globally and the symptoms have been identified at an early age. PMID- 26668784 TI - Nailfold capillaroscopic changes in Kindler syndrome. AB - Kindler syndrome (KS), the fourth major type of hereditary epidermolysis bullosa (HEB), is a rare, autosomal recessive disorder characterized by skin fragility and blistering at birth followed by development of marked photosensitivity and progressive poikilodermatous skin changes in later years. We reported here the case of a 54-year-old woman, who fulfills the diagnostic criteria of KS type of HEB, putting accent on the nailfold capillaroscopic changes. Using videocapillaroscopy we observed pronounced alterations in finger nail capillaries including reduction in capillary density, features of neoangiogenesis (architectural derangement, elongated loops, extremely tortuous, bushy or branching capillaries, thin, branching and interconnected capillaries), enlarged and giant capillaries. We consider the changes observed as an adaptive mechanism that compensate the loss of capillaries due to chronic periungual trauma. Further studies with larger number of patients are needed to confirm the significance of capillaroscopy findings for patients with HEB. PMID- 26668785 TI - China takes an active role in combating an Ebola outbreak: On-site observations and reflections from a Chinese healthcare provider. AB - As one of the active participants in the global fight against the 2014 outbreak of Ebola virus disease (EVD) in West Africa, China supplied many resources, including medical experts and scientists as well as medical supplies, to the affected countries. A member of the first contingent of Chinese public health experts who worked in Sierra Leone for 65 days, I am pleased to have this opportunity to review the major work done by our team to help deal with the Ebola epidemic in Sierra Leone. This is the first time that a Chinese public health training team has worked in West Africa. The team provides trainings for people from local communities in an effort to encourage local residents to get involved in the war against Ebola. However, the implementation of active measures against Ebola in West Africa was hampered somewhat by certain drawbacks in the area in terms of the health system, the shortage of medical resources, the high illiteracy rate, unhealthy lifestyles, and traditional funeral rites. All of these aspects need to be gradually improved in the aftermath of Ebola, and I believe that this is an area in which the Chinese public health system can play an important role. PMID- 26668786 TI - Unilateral gynaecomastia in a 16-month-old boy with neurofibromatosis type 1 - case report and brief review of the literature. AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that shows high penetrance with a wide variability in the phenotype. Prepubertal enlargement of the breast in male subjects affected by this condition is well known, but rarely reported. The present case report describes diagnosis and therapy of unilateral gynaecomastia in a toddler showing integumental stigmata of NF1. Furthermore, the report provides a brief review of the literature concerning this finding in NF1. According to this review, the present case appears to be one of the youngest NF1 affected males affected by gynaecomastia that has been reported. PMID- 26668788 TI - Can AIMS65 Save the Endoscopists from Midnight Calls? PMID- 26668787 TI - Racial and Ethnic Health Disparities and the Affordable Care Act: a Status Update. AB - Persistent racial and ethnic health disparities exist in the USA, despite decades of research and public health initiatives. Several factors contribute to health disparities, including (but not limited to) implicit provider bias, access to health care, social determinants, and biological factors. Disparities in health by race/ethnicity are unacceptable and correctable. The Patient Protection and Affordable Care Act is a comprehensive legislation that is focused on improving health care access, quality, and cost control. This health care reform includes specific provisions which focus on preventive care, the standardized collection of data on race, ethnicity, primary language and disability status, and health information technology. Although some provisions of the Patient Protection and Affordable Care Act have not been implemented, such as funding for the U.S. Public Health Sciences track, which would have addressed the shortage of medical professionals in the USA who are trained to use patient-centered, interdisciplinary, and care coordination approaches, this legislation is still poised to make great strides toward eliminating health disparities. The purpose of this manuscript is to highlight the unprecedented opportunities that exist for the Patient Protection and Affordable Care Act to reduce racial and ethnic disparities in health in the USA. PMID- 26668789 TI - Narrow Band Imaging as an Efficient and Economical Tool in Diagnosing Colorectal Polyps. PMID- 26668790 TI - Can Endoscopic Nasobiliary Drainage Involving Two Catheters Be Used to Treat Various Conditions? PMID- 26668791 TI - The Past, Present, and Future of Image-Enhanced Endoscopy. AB - Despite the remarkable progress recently made to enhance the resolution of white light endoscopy, detection, and diagnosis of premalignant lesions, such as adenomas and subtle early-stage cancers, remains a great challenge. As for example, although chromoendoscopy, such as endoscopy using indigo carmine, is useful for the early diagnosis of subtle lesions, the technique presents various disadvantages ranging from the time required for spray application of the dye and suctioning of excess dye to the increased difficulty in identifying lesions in the presence of severe inflammation and obstruction of visual field due to the pooling of solution in depressed-type lesions. To overcome these diagnostic problems associated with chromoendoscopy, research has focused on the development of endoscopes based on new optical technologies. Several types of image-enhanced endoscopy methods have recently been presented. In particular, image-enhanced endoscopy has emerged as a new paradigm for the diagnosis of gastrointestinal disorders. Image-enhanced endoscopes provide high-contrast images of lesions by means of optical or electronic technologies, including the contrast enhancement of the mucosal surface and of blood vessels. Chromoendoscopy, narrow-band imaging, i-SCAN, and flexible spectral imaging color enhancement are representative examples of image-enhanced endoscopy discussed in this paper. PMID- 26668792 TI - Narrow Band Imaging: Technology Basis and Research and Development History. AB - The first launch of narrow band imaging (NBI) was in 2005. Since then, in most countries where gastrointestinal endoscopies are performed, NBI is the most commonly used optical digital method of performing image-enhanced endoscopy. Thanks to the outstanding efforts of many endoscopists, many clinical studies have been performed and clinical evidence has been gathered. In Japan, since 2010, NBI has been reimbursed under the Japanese national health insurance system. This is owing to the establishment of clinical evidence by physicians. However, even though endoscope systems with NBI function have been widely used outside of Japan, dissemination of knowledge on how to use NBI is insufficient. In this review paper, the technology basis of NBI and its research and development history are described. I hope this information will be helpful for updating physicians' knowledge of NBI. PMID- 26668793 TI - Clinical Application of Magnifying Endoscopy with Narrow-Band Imaging in the Stomach. AB - Magnifying endoscopy with narrow-band imaging (M-NBI) can visualize superficial microanatomies in the stomach. The normal morphology of the microanatomy visualized by M-NBI differs according to the part of the stomach. The gastric fundic glandular mucosa appears as a regular honeycomb-like subepithelial capillary network (SECN) pattern with a regular collecting venule pattern and regular oval crypt opening with circular marginal crypt epithelium (MCE) pattern. The gastric pyloric glandular mucosa displays a regular coil-shaped SECN pattern and regular polygonal or curved MCE pattern. For a diagnosis of early gastric cancer using M-NBI, the vessel plus surface classification system was developed. This system is clinically useful for the differential diagnosis of focal gastritis and small depressed cancer and for determining the horizontal extent of early gastric cancer for successful endoscopic resection. Advantages of M-NBI over conventional endoscopic imaging techniques with white light include accurate diagnosis and cost effectiveness. This technique is a breakthrough in the endoscopic diagnostic field. PMID- 26668794 TI - Polyp Detection, Characterization, and Management Using Narrow-Band Imaging with/without Magnification. AB - Narrow-band imaging (NBI) is a new imaging technology that was developed in 2006 and has since spread worldwide. Because of its convenience, NBI has been replacing the role of chromoendoscopy. Here we review the efficacy of NBI with/without magnification for detection, characterization, and management of colorectal polyps, and future perspectives for the technology, including education. Recent studies have shown that the next-generation NBI system can detect significantly more colonic polyps than white light imaging, suggesting that NBI may become the modality of choice from the beginning of screening. The capillary pattern revealed by NBI, and the NBI International Colorectal Endoscopic classification are helpful for prediction of histology and for estimating the depth of invasion of colorectal cancer. However, NBI with magnifying colonoscopy is not superior to magnifying chromoendoscopy for estimation of invasion depth. Currently, therefore, chromoendoscopy should also be performed additionally if deep submucosal invasive cancer is suspected. If endoscopists become able to accurately estimate colorectal polyp pathology using NBI, this will allow adenomatous polyps to be resected and discarded; thus, reducing both the risk of polypectomy and costs. In order to achieve this goal, a suitable system for education and training in in vivo diagnostics will be necessary. PMID- 26668795 TI - Advanced Imaging Technology in Biliary Tract Diseases:Narrow-Band Imaging of the Bile Duct. AB - Newly introduced direct peroral cholangioscopy and the development of video choledochoscopes have enabled more defined observation of bile duct mucosal lesions with clearer images. Narrow-band imaging (NBI) is a unique endoscopic imaging technology that provides enhanced endoscopic images of surface mucosal structures and its superficial microvessels. Advanced cholangioscopy and NBI are expected to be useful for precise evaluation and correct diagnosis of biliary tract diseases. However, the diagnostic value of advanced bile duct imaging with cholangioscopy requires further evaluation. PMID- 26668796 TI - Advanced Imaging Technology Other than Narrow Band Imaging. AB - To improve the detection rate of gastrointestinal tumors, image-enhanced endoscopy has been widely used during screening and surveillance endoscopy in Korea. In addition to narrow band imaging (NBI) with/without magnification, various types of electronic chromoendoscopies have been used, including autofluorescence imaging, I-scan, and flexible spectral imaging color enhancement. These technologies enable the accurate characterization of tumors because they enable visualization of microvascular and microsurface patterns. The present review focuses on understanding the principle and clinical applications of advanced imaging technologies other than NBI. PMID- 26668797 TI - Usefulness and Future Prospects of Confocal Laser Endomicroscopy for Gastric Premalignant and Malignant Lesions. AB - Confocal laser endomicroscopy (CLE) is a new technology enabling endoscopists to visualize tissue at the cellular level. CLE has the fundamental potential to provide a histologic diagnosis, and may theoretically replace or reduce the need for performing biopsy for histology. The clinical benefits of CLE are more obvious in esophageal disease, including Barrett's esophagus. Currently, this technology has been adapted to the diagnosis and surveillance of Barrett's esophagus and related neoplasia. Standard white light endoscopy is the primary tool for gastric cancer screening. Currently, the only method available to precisely diagnose these lesions is upper endoscopy with an appropriate biopsy. A recent study showed that CLE could characterize dysplasia or cancer and identify the risk factors for gastric cancer, such as intestinal metaplasia and the presence of Helicobacter pylori in vivo, although fewer studies on CLE were performed on the stomach than on Barrett's esophagus and other esophageal diseases. However, the application of CLE to routine clinical endoscopy continues to be refined. This review focused on the usefulness and future prospects of CLE for gastric premalignant and malignant lesions. PMID- 26668798 TI - An Ultrathin Endoscope with a 2.4-mm Working Channel Shortens the Esophagogastroduodenoscopy Time by Shortening the Suction Time. AB - BACKGROUND/AIMS: Poor suction ability through a narrow working channel prolongs esophagogastroduodenoscopy (EGD). The aim of this study was to evaluate suction with a new ultrathin endoscope (EG-580NW2; Fujifilm Corp.) having a 2.4-mm working channel in clinical practice. METHODS: To evaluate in vitro suction, 200 mL water was suctioned and the suction time was measured. The clinical data of 117 patients who underwent EGD were retrospectively reviewed on the basis of recorded video, and the suction time was measured by using a stopwatch. RESULTS: In vitro, the suction time with the EG-580NW2 endoscope was significantly shorter than that with the use of an ultrathin endoscope with a 2.0-mm working channel (EG-580NW; mean +/- standard deviation, 22.7+/-1.1 seconds vs. 34.7+/-2.2 seconds; p<0.001). We analyzed the total time and the suction time for routine EGD in 117 patients (50 in the EG-580NW2 group and 67 in the EG-580NW group). In the EG-580NW2 group, the total time for EGD was significantly shorter than that in the EG-580NW group (275.3+/-42.0 seconds vs. 300.6+/-46.5 seconds, p=0.003). In the EG-580NW2 group, the suction time was significantly shorter than that in the EG-580NW group (19.2+/-7.6 seconds vs. 38.0+/-15.9 seconds, p<0.001). CONCLUSIONS: An ultrathin endoscope with a 2.4-mm working channel considerably shortens the routine EGD time by shortening the suction time, in comparison with an endoscope with a 2.0-mm working channel. PMID- 26668799 TI - The AIMS65 Score Is a Useful Predictor of Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding: Urgent Endoscopy in Patients with High AIMS65 Scores. AB - BACKGROUND/AIMS: To validate the AIMS65 score for predicting mortality of patients with nonvariceal upper gastrointestinal bleeding and to evaluate the effectiveness of urgent (<8 hours) endoscopic procedures in patients with high AIMS65 scores. METHODS: This was a 5-year single-center, retrospective study. Nonvariceal, upper gastrointestinal bleeding was assessed by using the AIM65 and Rockall scores. Scores for mortality were assessed by calculating the area under the receiver-operating characteristic curve (AUROC). Patients with high AIMS65 scores (>=2) were allocated to either the urgent or non-urgent endoscopic procedure group. In-hospital mortality, success of endoscopic procedure, recurrence of bleeding, admission period, and dose of transfusion were compared between groups. RESULTS: A total of 634 patients were analyzed. The AIMS65 score successfully predicted mortality (AUROC=0.943; 95% confidence interval [CI], 0.876 to 0.99) and was superior to the Rockall score (AUROC=0.856; 95% CI, 0.743 to 0.969) in predicting mortality. The group with high AIMS65 score included 200 patients. The urgent endoscopic procedure group had reduced hospitalization periods (p<0.05). CONCLUSIONS: AIMS65 score may be useful in predicting mortality in patients with nonvariceal upper gastrointestinal bleeding. Urgent endoscopic procedures in patients with high scores may be related to reduced hospitalization periods. PMID- 26668800 TI - A Randomized Controlled Clinical Study Comparing the Diagnostic Accuracy of the Histologic Prediction for Colorectal Polyps Depending on the Use of Either Magnified or Nonmagnified Narrow Band Imaging. AB - BACKGROUND/AIMS: The aim of this study was to compare the diagnostic capabilities of narrow band imaging (NBI) colonoscopy with and without optical magnification in differentiating neoplastic from nonneoplastic colorectal polyps. METHODS: Between April 2012 and March 2013, 122 patients with colorectal polyps detected by using diagnostic conventional colonoscopy were prospectively enrolled. A total of 236 polyps were evaluated with NBI, in vivo in real time during therapeutic colonoscopy, by one experienced endoscopist. Whether magnification was used or not was determined by randomization. After an in vivo real-time endoscopic prediction of histology, all lesions were endoscopically excised. Surgical pathologic reports were used as the criterion standards. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of identifying neoplastic polyps were calculated. RESULTS: A total of 236 lesions with an average size of 5.6 mm in 122 patients were assessed (159 neoplastic, 77 nonneoplastic). The Sn, Sp, PPV, and NPV in differentiating neoplastic from nonneoplastic lesions with the magnified NBI were 97.5%, 83.3%, 94.0%, and 92.6%, respectively, whereas those of the nonmagnified NBI group were 97.5%, 85.1%, 91.7%, and 95.2%, respectively. CONCLUSIONS: Nonmagnified NBI colonoscopy distinguishes neoplastic from nonneoplastic colorectal polyps as accurately as does magnified NBI colonoscopy. PMID- 26668801 TI - Endoluminal Closure of Colon Perforation with Endoscopic Band Ligation: Technical Feasibility and Safety in an In Vivo Canine Model. AB - BACKGROUND/AIMS: Endoscopic band ligation (EBL) is an accepted method in the management of variceal bleeding; however, there is little evidence on the safety and feasibility of EBL for the closure of bowel perforation. In this study, we aimed to evaluate the technical feasibility and efficacy of EBL in iatrogenic colon perforation by using a canine model. METHODS: We established an iatrogenic colon perforation model by using seven beagle dogs. Longitudinal 1.5- to 1.7-cm colon perforations were created with a needle knife and an insulated-tip knife, and the perforation was subsequently closed with EBL. During a 2-week follow-up period, the animals were carefully monitored and then euthanized for pathologic examination. RESULTS: The EBL of iatrogenic colon perforations was successful in all dogs. The mean procedure time for EBL closure with one to three bands was 191.7 seconds, and there were no immediate complications. One animal was euthanized after 3 days because of peritonitis. There were no clinical and laboratory features of sepsis or peritonitis in the remaining six animals. On necropsy, we did not find any fecal peritonitis, pericolonic abscess formation, or transmural dehiscence at the perforation site. Histopathology demonstrated inflamed granulation tissue and scar lesions replaced by fibrosis. CONCLUSIONS: EBL might be a feasible and safe method for the management of iatrogenic colon perforations in an in vivo model. PMID- 26668802 TI - The Clinical Usefulness of Simultaneous Placement of Double Endoscopic Nasobiliary Biliary Drainage. AB - BACKGROUND/AIMS: To evaluate the technical feasibility and clinical efficacy of double endoscopic nasobiliary drainage (ENBD) as a new method of draining multiple bile duct obstructions. METHODS: A total of 38 patients who underwent double ENBD between January 2004 and February 2010 at the Asan Medical Center were retrospectively analyzed. We evaluated indications, laboratory results, and the clinical course. RESULTS: Of the 38 patients who underwent double ENBD, 20 (52.6%) had Klatskin tumors, 12 (31.6%) had hepatocellular carcinoma, 3 (7.9%) had strictures at the anastomotic site following liver transplantation, and 3 (7.9%) had acute cholecystitis combined with cholangitis. Double ENBD was performed to relieve multiple biliary obstruction in 21 patients (55.1%), drain contrast agent filled during endoscopic retrograde cholangiopancreatography in 4 (10.5%), obtain cholangiography in 4 (10.5%), drain hemobilia in 3 (7.9%), relieve Mirizzi syndrome with cholangitis in 3 (7.9%), and relieve jaundice in 3 (7.9%). CONCLUSIONS: Double ENBD may be useful in patients with multiple biliary obstructions. PMID- 26668803 TI - Esophageal Lymphoepithelioma-Like Carcinoma with Unique Daisy-Like Appearance. AB - Due to differences in prognosis and management, it is important to subclassify esophageal carcinoma. Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare, with only a few cases reported to date. Review of the literature revealed case reports describing lesions with similar histology. We present a 69 year-old man with a giant pedunculated-polypoid lesion of the esophagus shrinking the lumen. Endoscopic excision of the tumor was performed and final histopathological diagnosis was confirmed to be LELC. In contrast to a previous case with a more aggressive course and a recurrent lesion, our patient died of his disease within 8 months of diagnosis. Here we discuss the endoscopic and radiologic findings of the case and a review of the literature. PMID- 26668805 TI - Eosinophilic Gastritis Presenting as Tissue Necrosis. AB - Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID- 26668804 TI - Endoscopic Submucosal Dissection for Recurrent or Residual Superficial Esophageal Cancer after Chemoradiotherapy: Two Cases. AB - We report two cases of endoscopic submucosal dissection (ESD) for recurrent or residual esophageal squamous cell carcinoma (ESCC) lesions after chemoradiotherapy for advanced esophageal cancer. Case 1 involved a 64-year-old man who had previously undergone chemoradiotherapy for advanced ESCC and achieved a complete response (CR) for 22 months, until metachronous recurrent superficial ESCC was detected on follow-up esophagogastroduodenoscopy (EGD). We performed ESD and found no evidence of recurrence for 24 months. Case 2 involved a 59-year-old man who had previously undergone chemoradiotherapy for advanced ESCC. He responded favorably to treatment, and most of the tumor had disappeared on follow up EGD 4 months later. However, there were two residual superficial esophageal lugol-voiding lesions. We performed ESD, and he had a CR for 32 months thereafter. ESD can be considered a viable treatment option for recurrent or residual superficial ESCC after chemoradiotherapy for advanced esophageal cancer. PMID- 26668806 TI - Utility of Over-the-Scope Clipping for Closure of a Persistent Post-Percutaneous Endoscopic Gastrostomy Fistula under Long-Term Steroid Therapy. AB - A 50-year-old woman had a percutaneous endoscopic gastrostomy (PEG) tube placed after surgery for pharyngeal cancer. After 21 months, the PEG tube was removed due to improvement of per-oral ingestion. She had taken prednisolone for 31 years for systemic lupus erythematosus. The post-PEG fistula did not close spontaneously. The cause of the fistula was slow wound healing and gastrostomy site inflammation due to long-term steroid therapy. We were able to close the fistula with an over-the-scope clipping (OTSC) system. This case suggests that OTSC is useful for closing persistent post-PEG fistulas in patients receiving long-term prednisolone therapy. PMID- 26668807 TI - Delayed Pneumoperitoneum and Acute Pulmonary Edema Secondary to Acute Gastric Dilatation. AB - Pneumoperitoneum caused by acute gastric dilatation (AGD) is a very rare complication. We report a case of pneumoperitoneum and acute pulmonary edema caused by AGD in a patient with Parkinson's disease. A 78-year-old woman presented with pneumonia and AGD. We inserted a nasogastric tube and administered empirical antibiotics. We performed an endoscopy, and perforation or necrosis of the stomach and pyloric stenosis were not observed. Thirty-six hours after admission, the patient suddenly developed dyspnea and shock, and eventually died. We suspected the cause of death was pneumoperitoneum and acute pulmonary edema caused by AGD during the conservative treatment period. Immunocompromised patients with chronic illness require close observation even if they do not show any symptoms suggestive of complications. Even if the initial endoscopic or abdominal radiologic findings do not show gastric necrosis or perforation, follow up with endoscopy is essential to recognize complications of AGD early. PMID- 26668808 TI - Unexpected Delayed Colon Perforation after the Endoscopic Submucosal Dissection with Snaring of a Laterally Spreading Tumor. AB - Colonic perforation may occur as a complication of diagnostic and therapeutic colonoscopy. The risk factors for perforation after colorectal endoscopic submucosal dissection (ESD) include an inexperienced endoscopist, a large tumor size, and submucosal fibrosis. The mechanisms of perforation include unintended endoscopic resection/dissection and severe thermal injury. Here, we report a case of colon perforation that occurred after ESD with snaring of a laterally spreading tumor. The perforation was completely unexpected because there were no colorectal ESD-associated risk factors for perforation, deep dissection, or severe coagulation injury in our patient. PMID- 26668809 TI - Successful Palliation of a Malignant Cologastric Fistula with a Covered Self Expanding Metal Stent. AB - When patients present with malignant cologastric fistulas, the tumor stage is often advanced and management is only palliative. We report the case of a 75-year old man with a symptomatic cologastric fistula arising from an advanced tumor in the transverse colon, previously stented owing to malignant obstruction. An 8-cm long covered self-expanding metal stent (COMVI enteral colonic stent; Taewoong Medical) was placed inside the primary stent, which sealed the fistula and completely alleviated the symptoms. Considering the successful outcome, we propose that insertion of a covered stent be considered in the palliative management of patients with malignant cologastric fistulas. PMID- 26668810 TI - Endoscopic Extraction of Biliary Fascioliasis Diagnosed Using Intraductal Ultrasonography in a Patient with Acute Cholangitis. AB - Fasciola hepatica infection may result in biliary obstruction with or without cholangitis in the chronic biliary phase. Because clinical symptoms and signs of F. hepatica are similar to other biliary diseases that cause bile duct obstruction, such as stones or bile duct malignancies, that are, in fact, more common, this condition may not be suspected and diagnosis may be overlooked and delayed. Patients undergoing endoscopic retrograde cholangiopancreatography or endoscopic ultrasonography for the evaluation of bile duct obstruction may be incidentally detected with the worm, and diagnosis can be confirmed by extraction of the leaf-like trematode from the bile duct. Intraductal ultrasonography (IDUS) can provide high-resolution cross-sectional images of the bile duct, and is useful in evaluating indeterminate biliary diseases. We present a case of biliary fascioliasis that was diagnosed using IDUS and managed endoscopically in a patient with acute cholangitis. PMID- 26668811 TI - A Case Report of Rash at Peritoneal Dialysis Exit Site. AB - The International Society for Peritoneal Dialysis recommends the regular application of topical antibiotic-containing preparations in addition to a routine exit site care to reduce the risk of exit site infection (ESI). Among these prophylactic antimicrobial preparations, topical gentamicin is one of the widely used and effective antibiotics for prevention of ESI and peritonitis in peritoneal dialysis (PD) patients. Overall, topical gentamicin is well tolerated; however, its use can be associated with the development of allergic contact dermatitis (ACD). We describe a first reported case of PD catheter exit site contact ACD due to topical gentamicin mimicking ESI. The patient in this report developed worsening violaceous in color and pruritic rash surrounding the PD catheter exit site that appeared 3 weeks after the initiation of gentamicin cream. The association between development of rash and initiation of topical gentamicin led to a suspicion of local reaction to gentamicin rather than ESI. Skin biopsy confirmed ACD. Discontinuation of the provoking agent and subsequent treatment with topical hydrocortisone application led to a resolution of the exit site rash. Any rash at a PD catheter exit site should be considered infectious until proven otherwise. However, it is important to be aware of noninfectious etiologies of exit site rashes as the treatment of these 2 conditions differs. PMID- 26668812 TI - Practically Saline. AB - Introduction. In December 2014, the Food and Drug Administration issued a recall of all Wallcur simulation products due to reports of their use in clinical practice. We present a case of septic shock and multiorgan failure after the accidental intravenous infusion of a nonsterile Wallcur simulation product. Case. The patient presented with symptoms of rigors and dyspnea occurring immediately after infusion of Wallcur Practi-0.9% saline. Initial laboratory evidence was consistent with severe septic shock and multiorgan dysfunction. His initial lactic acid level was 9 mmol/L (reference range = 0.5-2.2), and he had evidence of acute kidney injury and markers of disseminated intravascular coagulation. All 4 blood culture bottles isolated multidrug-resistant Empedobacter brevis. The patient recovered from his illness and was discharged with ciprofloxacin therapy per susceptibilities. Discussion. This patient represents the first described case of severe septic shock associated with the infusion of a Wallcur simulation product. Intravenous inoculation of a nonsterile fluid is rare and exposes the patient to unusual environmental organisms, toxins, or unsafe fluid characteristics such as tonicity. During course of treatment, we identified the possible culprit to be a multidrug-resistant isolate of Empedobacter brevis. We also discuss the systemic failures that led to this outbreak. PMID- 26668813 TI - Studying the mechanisms of language learning by varying the learning environment and the learner. AB - Language learning is a resilient process, and many linguistic properties can be developed under a wide range of learning environments and learners. The first goal of this review is to describe properties of language that can be developed without exposure to a language model - the resilient properties of language - and to explore conditions under which more fragile properties emerge. But even if a linguistic property is resilient, the developmental course that the property follows is likely to vary as a function of learning environment and learner, that is, there are likely to be individual differences in the learning trajectories children follow. The second goal is to consider how the resilient properties are brought to bear on language learning when a child is exposed to a language model. The review ends by considering the implications of both sets of findings for mechanisms, focusing on the role that the body and linguistic input play in language learning. PMID- 26668814 TI - Simultaneous Human Immunodeficiency Virus-Hepatitis B-Hepatitis C Point-of-Care Tests Improve Outcomes in Linkage-to-Care: Results of a Randomized Control Trial in Persons Without Healthcare Coverage. AB - Background. In Europe and the United States, more than two thirds of individuals infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and 15%-30% of human immunodeficiency virus (HIV)-positive individuals are unaware of their infection status. Simultaneous HIV-, HBV-, and HCV-rapid tests could help improve infection awareness and linkage-to-care in particularly vulnerable populations. Methods. The OptiScreen III study was a single-center, randomized, control trial conducted at a free clinic ("Medecins du Monde", Paris, France). Participants were randomized 1:1 to receive 1 of 2 interventions testing for HIV, HBV, and HCV: standard serology-based testing (S-arm) or point-of-care rapid testing (RT arm). The main study endpoints were the proportion of participants who became aware of their HIV, HBV, and HCV status and who were linked to care when testing positive. Results. A total of 324 individuals, representing mainly African immigrants, were included. In the S-arm, 115 of 162 (71.0%) participants performed a blood draw and 104 of 162 (64.2%) retrieved their test result. In comparison, 159 of 162 (98.2%) of participants randomized to the RT-arm obtained their results (P < .001). Of the 38 (11.7%) participants testing positive (HIV, n = 7; HBV, n = 23; HCV, n = 8), 15 of 18 (83.3%) in the S-arm and 18 of 20 (90.0%) in the RT-arm were linked-to-care (P = .7). In post hoc analysis assuming the same disease prevalence in those without obtaining test results, difference in linkage-to-care was more pronounced (S-arm = 60.0% vs RT-arm = 90.0%; P = .04). Conclusions. In a highly at-risk population for chronic viral infections, the simultaneous use of HIV, HBV, and HCV point-of-care tests clearly improves the "cascade of screening" and quite possibly linkage-to-care. PMID- 26668815 TI - A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease. AB - We developed a "virtual clinic" to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID- 26668817 TI - Toward real-time remote processing of laparoscopic video. AB - Laparoscopic surgery is a minimally invasive surgical technique where surgeons insert a small video camera into the patient's body to visualize internal organs and use small tools to perform surgical procedures. However, the benefit of small incisions has a drawback of limited visualization of subsurface tissues, which can lead to navigational challenges in the delivering of therapy. Image-guided surgery uses the images to map subsurface structures and can reduce the limitations of laparoscopic surgery. One particular laparoscopic camera system of interest is the vision system of the daVinci-Si robotic surgical system (Intuitive Surgical, Sunnyvale, California). The video streams generate approximately 360 MB of data per second, demonstrating a trend toward increased data sizes in medicine, primarily due to higher-resolution video cameras and imaging equipment. Processing this data on a bedside PC has become challenging and a high-performance computing (HPC) environment may not always be available at the point of care. To process this data on remote HPC clusters at the typical 30 frames per second (fps) rate, it is required that each 11.9 MB video frame be processed by a server and returned within 1/30th of a second. The ability to acquire, process, and visualize data in real time is essential for the performance of complex tasks as well as minimizing risk to the patient. As a result, utilizing high-speed networks to access computing clusters will lead to real-time medical image processing and improve surgical experiences by providing real-time augmented laparoscopic data. We have performed image processing algorithms on a high-definition head phantom video (1920 * 1080 pixels) and transferred the video using a message passing interface. The total transfer time is around 53 ms or 19 fps. We will optimize and parallelize these algorithms to reduce the total time to 30 ms. PMID- 26668816 TI - Optimized multimodal functional magnetic resonance imaging/near-infrared spectroscopy probe for ultrahigh-resolution mapping. AB - Functional near-infrared spectroscopy (fNIRS) is an increasingly important noninvasive method in neuroscience due to its high temporal resolution and ability to independently measure oxy- and deoxy-hemoglobin. However, the relatively low spatial resolution of fNIRS makes it difficult to relate this signal to underlying anatomy. Simultaneous functional magnetic resonance imaging (fMRI) can complement fNIRS with superior spatial resolution and the ability to image the entire brain, providing additional information to improve fNIRS localization. However, current simultaneous fMRI/fNIRS acquisition methods are not optimal, due to the poor physical compatibility of existing MR coils and fNIRS optodes. Here, we present a technique to manufacture a true multimodal fMRI/fNIRS probe in which both modalities can be used with maximal sensitivity. To achieve this, we designed custom MR coils with integral fNIRS optodes using three-dimensional printing. This multimodal probe can be used to optimize spatial ([Formula: see text]) and temporal resolution (2.5 Hz) of fMRI, and it provides maximal MRI sensitivity, while allowing for high flexibility in the location and density of fNIRS optodes within the area of interest. Phantom and human data are shown to confirm the improvement in sensitivity in both modalities. This probe shows promise for addressing fundamental questions of the relation of fNIRS to physiology. PMID- 26668818 TI - Myositis-specific autoantibodies are specific for myositis compared to genetic muscle disease. AB - OBJECTIVE: To determine the specificity of myositis-specific autoantibodies (MSAs) for autoimmune myopathy compared with inherited muscle diseases. METHODS: Serum samples from 47 patients with genetically confirmed inherited muscle diseases were screened for the most common MSAs, including those recognizing TIF1gamma, NXP2, Mi2, MDA5, Jo1, SRP, and HMGCR. We compared these results with the findings in a cohort of patients with dermatomyositis (DM) previously screened for anti-TIF1gamma, -NXP2, -Mi2, -MDA5, and -Jo1. RESULTS: Overall, the presence of anti-TIF1gamma, -NXP2, -Mi2, -MDA5, or -Jo1 was 96% specific and 67% sensitive for DM compared to patients with genetic muscle diseases. No patients with inherited muscle disease had anti-SRP or anti-HMGCR autoantibodies. Only 2 patients with genetic muscle disease had a MSA. One patient with anti-Mi2 autoantibodies had both genetically confirmed facioscapulohumeral dystrophy and dermatomyositis based on a typical skin rash and partial response to immunosuppressive medications. A second patient with anti-Jo-1 autoantibodies had both genetically defined limb-girdle muscular dystrophy type 2A (i.e., calpainopathy) and a systemic autoimmune process based on biopsy-confirmed lupus nephritis, sicca symptoms, and anti-Ro52 autoantibodies. CONCLUSIONS: The MSAs tested for in this study are highly specific for autoimmune muscle disease and are rarely, if ever, found in patients who only have genetic muscle disease. In patients with genetic muscle disease, the presence of a MSA should suggest the possibility of a coexisting autoimmune process. PMID- 26668819 TI - Spatiotemporal ablation of CXCR2 on oligodendrocyte lineage cells: Role in myelin repair. AB - BACKGROUND: Residual CXCR2 expression on CNS cells in Cxcr2 (+/-) ->Cxcr2 (-/-) chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizone-induced demyelination. METHODS: We generated Cxcr2 (fl/-) :PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2 (fl/-) :PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosphatidylcholine (LPC) treatment of cerebellar slice cultures. RESULTS: Cxcr2 (fl/-) :PLPCre-ER(T)(+) (termed Cxcr2-cKO) mice showed better myelin repair 4 days after LPC-induced demyelination of cerebellar slice cultures. Cxcr2-cKOs also displayed enhanced hippocampal remyelination after a 2 week recovery from 6-week cuprizone feeding. CONCLUSION: Using 2 independent demyelination/remyelination models, our data document enhanced myelin repair in Cxcr2-cKO mice, consistent with the data obtained from radiation chimerism studies of germline CXCR2. Further experiments are appropriate to explore how CXCR2 function in the oligodendrocyte lineage accelerates myelin repair. PMID- 26668820 TI - Autoimmunity: The good, the bad, and the ugly. PMID- 26668822 TI - Aggressive recurrence of primary hepatic epithelioid hemangioendothelioma after liver transplantation. PMID- 26668824 TI - Distribution of hepatitis C risk factors and hepatitis C treatment outcomes among central Canadian Aboriginals. PMID- 26668823 TI - Serum triglyceride level - a predictor of complications and outcomes in acute pancreatitis? PMID- 26668825 TI - Colonic interposition between the liver and right diaphragm: The 'Chilaiditi sign'. PMID- 26668821 TI - AMPA Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete Spinal Cord Injury. AB - Clinical spinal cord injury (SCI) is accompanied by comorbid peripheral injury in 47% of patients. Human and animal modeling data have shown that painful peripheral injuries undermine long-term recovery of locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity in dorsal horn sensory systems through AMPA receptor (AMPAR) phosphorylation and trafficking to synapses. Here we test whether ventral horn motor neurons in rats demonstrate similar experience-dependent maladaptive plasticity below a complete SCI in vivo. Quantitative biochemistry demonstrated that intermittent nociceptive stimulation (INS) rapidly and selectively increases AMPAR subunit GluA1 serine 831 phosphorylation and localization to synapses in the injured spinal cord, while reducing synaptic GluA2. These changes predict motor dysfunction in the absence of cell death signaling, suggesting an opportunity for therapeutic reversal. Automated confocal time-course analysis of lumbar ventral horn motor neurons confirmed a time-dependent increase in synaptic GluA1 with concurrent decrease in synaptic GluA2. Optical fractionation of neuronal plasma membranes revealed GluA2 removal from extrasynaptic sites on motor neurons early after INS followed by removal from synapses 2 h later. As GluA2-lacking AMPARs are canonical calcium-permeable AMPARs (CP-AMPARs), their stimulus- and time dependent insertion provides a therapeutic target for limiting calcium-dependent dynamic maladaptive plasticity after SCI. Confirming this, a selective CP-AMPAR antagonist protected against INS-induced maladaptive spinal plasticity, restoring adaptive motor responses on a sensorimotor spinal training task. These findings highlight the critical involvement of AMPARs in experience-dependent spinal cord plasticity after injury and provide a pharmacologically targetable synaptic mechanism by which early postinjury experience shapes motor plasticity. PMID- 26668826 TI - A retrospective study of the clinical burden of hospitalized all-cause and pneumococcal pneumonia in Canada. PMID- 26668827 TI - Quality improvement in critical care: Selection and development of quality indicators. PMID- 26668828 TI - Predictors of poor outcomes in critically ill patients with hematological malignancy. PMID- 26668829 TI - Serving primary health care. PMID- 26668830 TI - Ageing positively for New Zealanders. PMID- 26668831 TI - The association between living alone and frailty in a rural Japanese population: the Nagasaki Islands study. AB - INTRODUCTION: Demographic changes in Japan have resulted in an increased number of elderly living alone. AIM: The aim of this study was to identify if there is an association between frailty and living alone. METHODS: We conducted a cross sectional study of 1602 Japanese men and women living in isolated islands. Information obtained included height, body weight, handgrip strength, and family structure; antihypertensive, hypoglycaemic, and lipid-lowering medication use; history of stroke or ischaemic heart disease, smoking history, alcohol intake, joint pain or swelling. Relevant laboratory test results were obtained from recent health check-ups. The Frailty Index for Japanese elderly, a 15-item self report questionnaire was completed by participants and the Kessler Psychological Distress Scale (K6) was administered. RESULTS: After individuals aged below 60 years old or those with missing data were excluded, data from 1224 participants were analysed. Living alone (single household family structure) was significantly associated with frailty in men (odds ratio [OR] 3.85; 95% confidence interval [CI] 1.94-7.65), but not in women (OR 1.08; 95% CI 0.72-1.63). This association in men remained statistically significant after adjustment for known risk factors for frailty. DISCUSSION: In the elderly population in rural Nagasaki, men living alone have a high risk of frailty. Screening and intervention to prevent frailty in this population is urgently needed. PMID- 26668832 TI - Awareness, attitudes and practices of first aid among school teachers in Mangalore, south India. AB - INTRODUCTION: Circumstances requiring medical attention are common at schools. Teachers are often the first individuals to witness and handle situations requiring first aid and medical emergencies. AIM: To determine awareness, attitudes and practices of school teachers and the facilities available at schools with respect to administration of first aid. METHODS: Data were obtained from 146 teachers in nine schools in Mangalore, India, using a self-administered questionnaire. The schools were also inspected for first aid equipment and facilities. RESULTS: Only 69 (47%) teachers had received first aid training previously. Poor and moderate knowledge of first aid was observed among 19 (13%) and 127 (87%) teachers, respectively. Only eight teachers knew the correct procedure for cardiopulmonary resuscitation. Most teachers 96 (66%) were willing to administer first aid if provided with the required training. A total of 74 teachers reported having practised first aid in response to a situation arising at their school. Wounds (36%) and syncopal attack (23%) were among the commonly encountered situations requiring first aid management at schools. Teachers' confidence level in administering first aid was significantly associated with prior training in first aid (p=0.001). First aid kits were available in only five of the nine schools surveyed. DISCUSSION: The current competency level among teachers in Mangalore to administer first aid is inadequate. Measures need to be taken at schools to ensure initiation of first aid training followed by periodic training for teachers in first aid. PMID- 26668833 TI - Priorities and approaches to investigating Asian youth health: perspectives of young Asian New Zealanders. AB - INTRODUCTION: The proportion of young people in New Zealand identifying with Asian ethnicities has increased considerably. Despite some prevalent health concerns, Asian youth are less likely than non-Asian peers to seek help. As preparatory research towards a more nuanced approach to service delivery and public policy, this qualitative study aimed to identify young Asian New Zealanders' perspectives on best approaches to investigate health issues of priority concern to them. METHODS: Three semi-structured focus group discussions were conducted with 15 Asian youth leaders aged 18-24 years. Using an inductive approach for thematic analysis, key themes were identified and analysed. FINDINGS: Study participants considered ethno-cultural identity, racism and challenges in integration to play significant roles influencing the health of Asian youth (especially mental health) and their access to health services. While emphasising the importance of engaging young Asians in research and service development so that their needs and aspirations are met, participants also highlighted the need for approaches that are cognisant of the cultural, contextual and intergenerational dimensions of issues involved in promoting youth participation. CONCLUSION: Research that engages Asian youth as key agents using methods that are sensitive to their cultural and sociological contexts can inform more responsive health services and public policy. This is of particular relevance in primary health care where culturally competent services can mitigate risks of unmet health needs and social isolation. PMID- 26668834 TI - From 'pleasure to chemistry': the experience of carbohydrate counting with and without carbohydrate restriction for people with Type 1 diabetes. AB - INTRODUCTION: Matching carbohydrate intake with insulin dosage is recommended management for people with Type 1 diabetes. However, international interest in restricted carbohydrate diets is growing. General practitioners and practice nurses need to know how to advise people with Type 1 diabetes regarding low carbohydrate diets. This study aimed to explore the carbohydrate counting experiences of people with Type 1 diabetes in a trial with and without a diet restricted to 75 g of carbohydrate per day. METHODS: Eight participants were interviewed by focus group or interview 12 weeks after a carbohydrate counting course with individual dietary choice or the same course with information on restricted carbohydrate eating and a daily maximum intake of 75 g of carbohydrate. Data were analysed using a qualitative thematic analysis approach. FINDINGS: Themes included the need for insulin management skills, impact of the dietary experience, and need for dietary knowledge. The restricted-carbohydrate group encountered mealtime insulin resistance and difficulty managing insulin dosages when transitioning on and off the low-carbohydrate diet. The diet impacted on mood, feelings of satiety and it was reported that food changed from being 'a pleasure to chemistry'. Both groups described feeling empowered to manage their diabetes as a result of the carbohydrate counting course. CONCLUSION: Participants reported increased knowledge and challenging insulin management. The restricted-carbohydrate group reported mealtime insulin resistance and a strong dietary impact. Extra health professional support may be required, especially at dietary transition periods. More research is warranted into the reported mealtime insulin resistance. PMID- 26668835 TI - Proposals for registered nurse prescribing: perceptions and intentions of nurses working in primary health care settings. AB - INTRODUCTION: In 2013, the Nursing Council of New Zealand consulted on a proposal for introduction of registered nurse (RN) prescribing at two levels (specialist and community) within the designated class of prescriber. The proposal builds on the success of the diabetes nurse specialist prescribing project and the experience of other countries where RN prescribing is well established. AIM: To describe the views and intentions of nurses who work in primary health care (PHC) settings about the two levels of RN prescribing proposed. METHODS: The study involved a self-reported survey using a non-probability sample of RNs working in PHC settings (N=305). Quantitative and qualitative data were analysed descriptively. RESULTS: The respondents were experienced nurses. Overall, 82.3% expressed interest in becoming a community nurse prescriber, and 62.6% expressed interest in the specialist prescriber level. RN prescribing was expected to improve efficiency and access to medicines for high-needs populations, clarify accountability and improve nurses' autonomy. The education requirements for the specialist level were viewed as appropriate but too onerous for many. Requirements were viewed as inadequate for the community level. Concerns were raised about funding for education and support for RN prescribing roles. DISCUSSION: Nurses were positive about the proposals and see a potential to meet significant unmet health need. Nurses are already engaged in the provision of medicines to patients and prescribing authority would ensure they are suitably qualified to engage in these tasks. A clear policy platform will be needed if the proposed levels of RN prescribing are to be successfully implemented. PMID- 26668836 TI - Rural health care in New Zealand: the case of Coast to Coast Health Centre, Wellsford, an early Integrated Family Health Centre. AB - INTRODUCTION: Primary health care is critical, particularly in rural areas distant from secondary care services. AIM: To describe the development of Coast to Coast Health Centre (CTCHC) at Wellsford, north of Auckland, New Zealand and reflect on its achievements and ongoing challenges. METHODS: Interviews were conducted with staff and management of CTCHC and with other health service providers. Surveys of staff and a sample of enrolled patients were undertaken. Numerical data on service utilisation were obtained from the practice and from national datasets. RESULTS: The CTCHC provides a wide range of services, including after-hours care, maternity and radiology, across a network of electronically connected sites, as well as interdisciplinary training for a range of health students. General practitioner (GP) recruitment is problematic and nursing roles have been expanded. Staff report positively on the work environment. Consultation rates are higher than in comparable practices, especially consultations with nurses. Rates of hospital admission are relatively low. The development of the CTCHC was assisted by formation of a local primary health organisation (PHO) and by recognition by the local district health board (DHB). Issues with poor coordination of local services, and less service provision than is characteristic in urban areas, remain. Contracting processes with the DHB were complex and time-consuming. The merging of the local PHO into a larger PHO within the Waitemata DHB catchment inhibited progression towards more complete locality planning. DISCUSSION: A dedicated and locally controlled provider was able to generate a more than usually complete community health service for Wellsford and area. PMID- 26668838 TI - The contribution of dietitians to the primary health care workforce. AB - INTRODUCTION: Dietetic intervention is effective in the management of nutrition related conditions and their comorbidities. New Zealand has an increasing need for primary and preventive health care to reduce the burden of non-communicable disease. AIM: To review the recent evidence of effectiveness of dietetic intervention in primary health care on health and wider economic outcomes. Health benefits and cost benefits of employing dietitians to perform nutrition intervention in the primary health care setting are evaluated in the areas of obesity in conjunction with diabetes and cardiovascular disease, and malnutrition in older adults. METHODS: An electronic literature search of four scientific databases, websites of major dietetic associations and high-impact nutrition and dietetic journals was conducted. Randomised controlled trials and non-randomised studies conducted from 2000 to 2014 were included. RESULTS: Dietetic intervention demonstrates statistically and clinically significant impacts on health outcomes in the areas of obesity, cardiovascular disease, diabetes, and malnutrition in older adults, when compared to usual care. Dietitians working in primary health care can also have significant economic benefits, potentially saving the health care system NZ$5.50-$99 for every NZ$1 spent on dietetic intervention. DISCUSSION: New Zealand must look to new models of health care provision that are not only patient-centred but are also cost-effective. This review demonstrates that dietitians in primary health care can improve patients' health and quality of life. Increasing the number of dietitians working in primary health care has the potential to make quality nutrition care accessible and affordable for more New Zealanders. PMID- 26668837 TI - General practice registrars' views on maternity care in general practice in New Zealand. AB - INTRODUCTION: The number of general practitioners (GPs) providing maternity care in New Zealand has declined dramatically since legislative changes of the 1990s. The Ministry of Health wants GPs to provide maternity care again. AIM: To investigate New Zealand general practice registrars' perspectives on GPs' role in maternity care; specifically, whether maternity services should be provided by GPs, registrars' preparedness to provide such services, and training opportunities available or required to achieve this. METHODS: An anonymous online questionnaire was distributed to all registrars enrolled in The Royal New Zealand College of General Practitioners' (RNZCGP's) General Practice Education Programme (GPEP) in 2012, via their online learning platform OWL. RESULTS: 165 of the 643 general practice registrars responded (25.7% response rate). Most (95%) believe that GPs interested and trained in maternity care should consider providing antenatal, postnatal or shared care with midwives, and 95% believe women should be able to access maternity care from their general practice. When practising as a GP, 90% would consider providing antenatal and postnatal care, 47.3% shared care, and 4.3% full pregnancy care. Professional factors including training and adequate funding were most important when considering providing maternity care as a GP. DISCUSSION: Ninety-five percent of general practice registrars who responded to our survey believe that GPs should provide some maternity services, and about 90% would consider providing maternity care in their future practice. Addressing professional issues of training, support and funding are essential if more GPs are to participate in maternity care in New Zealand. PMID- 26668839 TI - A hidden jewel: social work in primary health care practice in Aotearoa New Zealand. AB - INTRODUCTION: The New Zealand (NZ) Ministry of Health's Primary Health Care Strategy (2001) has an overall vision of better health for all and the reduction of health inequalities between different population groups. This goal can be achieved by comprehensive, integrated primary health care (PHC) service delivery. One useful approach is to place social workers within PHC practices. This study aimed to explore the perceptions about, and the experiences gained by, such integrated social workers regarding their contributions towards the PHC vision. METHODS: This qualitative study focused on three participant groups, namely social workers, PHC professionals and key informants. Overall, 18 one-to-one, semi-structured interviews were undertaken in various locations in NZ. Key themes were identified via a general inductive approach. FINDINGS: Three key themes emerged from the data: wider factors, organisational factors and social work factors. The last theme encompassed the social workers' professional understanding, knowledge and approaches. The organisational factors (a community needs focus and provision of a supportive work environment) and the wider factors identified (funding and issues experienced by communities) had variable impact on these social work positions. CONCLUSION: Participants viewed social workers as facilitating appropriate access to and engagement by people with services; enhancing ongoing, coordinated, safe service provision; and contributing to staff development. The potential of the social work profession within PHC practices was well recognised by non-social worker participants. This study provides initial insights into the unique contributions made by social workers towards achieving NZ Ministry of Health's PHC vision. PMID- 26668840 TI - A regional programme to improve skin cancer management. AB - BACKGROUND AND CONTEXT: In 2008, public specialist and general practice services in Canterbury were unable to manage demand for skin cancer treatment. Local clinicians decided the solution was to develop a see-and-treat skin excision clinic staffed by plastic surgeons and general practitioners (GPs), and the introduction of subsidised excisions in general practice. This paper describes the collaboration between clinicians, managers and funders and the results and quality management measures of these initiatives. ASSESSMENT OF PROBLEM: There is an increasing incidence of skin cancer. GPs in Canterbury were unable to meet increasing demand for skin cancer treatment because some lacked confidence and competence in skin cancer management. There was no public funding for primary care management of skin cancer, driving patients to fully funded secondary care services. Secondary care services were at capacity, with no coordinated programme across primary and secondary care. RESULTS: The programme has resulted in a greater number of skin cancers being treated by the public health system, a reduction in waiting times for treatment, and fewer minor skin lesions being referred to secondary care. Quality measures have been achieved and are improving steadily. Development of the programme has improved working relationships between primary and secondary care clinicians. STRATEGIES FOR IMPROVEMENT: The strategy was to facilitate the working relationship between primary and secondary care and increase the capacity for skin lesion excisions in both sectors. LESSONS: Skin cancer management can be improved by a coordinated approach between primary and secondary care. PMID- 26668841 TI - Research with Pacific church communities: overdone or under-committed? PMID- 26668842 TI - PSA testing. PMID- 26668844 TI - [National and regional prevention plans: an opportunity that should not be wasted]. PMID- 26668843 TI - Simultaneous acquisition of infrared, fluorescence and light scattering spectra of proteins: direct evidence for pre-fibrillar species in amyloid fibril formation. AB - Different spectroscopic approaches are often used to probe specific aspects of amyloid fibril formation but are usually performed separately and under different conditions. This makes it problematic to relate different aspects of the aggregation process when these are monitored by different methods. We report on a multispectral approach for simultaneous acquisition of infrared, fluorescence and light scattering spectra of proteins undergoing aggregation. We have applied our approach to study beta-lactoglobulin, a milk protein known to form amyloid fibrils under well-established conditions. Our real-time multispectral measurements show that unfolding of this protein is followed by formation of early aggregates consisting of intermolecular beta-sheets with a typical infrared absorption at ~1619 cm(-1) in (2)H2O. These aggregates, which lead to an increase in the light scattering signal, do not bind the amyloid-specific fluorophore ThT and therefore consist of oligomers or protofibrils. Fibril growth is then observed as a sigmoidal increase in ThT fluorescence. After ~25 h, a plateau is observed in the intensities of ThT emission and of the band at 1619 cm(-1), indicating that no new fibrils are forming. However, a second phase in the light scattering signal taking place after ~25 h suggests that the fibrils are assembling into larger structures, known as mature fibrils. This is associated with an upshift of the main beta-sheet band in the infrared spectrum. TEM analyses confirmed the existence of thick fibrils comprising 3-5 filaments. PMID- 26668845 TI - Corrigendum to "Syndecan-4 ectocdomain evokes mobilization of podocyte TRPC6 channels and their associated pathways: An essential role for integrin signaling". PMID- 26668846 TI - The View of Religious Officials on Organ Donation and Transplantation in the Zeytinburnu District of Istanbul. AB - One of the obstacles to organ donation and transplantation in Turkey is that of religious beliefs and, at this point, religious officials constitute a key aspect of this problem. Positive or negative viewpoints held by religious officials regarding organ donation and transplantation are influential in guiding the public. This descriptive study was conducted for the purpose of describing religious officials' viewpoints on this subject. To determine the opinions of 40 religious officials from among the imams and muezzins working in Zeytinburnu District Mufti (Religious Officials Superior) Station who participated in a normal meeting in April and who fully completed the survey. A 27-question survey form was used that consisted of open-ended and closed questions, 5 of which were on socio-demographic characteristics, 13 on viewpoints on organ donation and transplantation, and 9 on the Islamic viewpoint regarding organ donation and transplantation. For the analysis of the results, Student's t test and one-way ANOVA tests were used. It was found that all of the religious officials believed in the importance of organ donation, 80 % considered donating their organs, and 5 % had made an organ donation. Of the religious officials who had not donated organs, 35 % gave an answer that there was no specific reason and 27.5 % stated that they had never considered the subject. While the number of those stating that they would donate the organs of a close associate who had died, 77.5 % of them who did not want to donate gave as their reason the idea that if it were him, he would perhaps not want to give his organs after death. Of the religious officials questioned, 92.5 % asserted that the religion of Islam looked positively on organ donation and transplantation, 55 % stated that the knowledge of religious officials in the country was inadequate regarding this subject, and 65 % said that for interest in organ donation to increase, religious officials should make speeches and raise the issue with the public in conversations, meetings, and sermons. Fully 85 % asserted that for interest in organ donation in Turkey to increase, religious officials have to lead on the subject. Of those questioned, 52.5 % considered their knowledge on organ donation and transplantation to be adequate and that they had obtained 52.5 % of such information from seminars/conferences, 50 % from television/radio, and 45 % from Directorate of Religious Affairs publications. However, 40 % expressed that they did not know where organ donations were made. One reason for inadequate organ donation in Turkey is that of incorrect religious beliefs. Thus, it is necessary that informative efforts are made by the Directorate of Religious Affairs through in-house training programs, and that healthcare, religious, and legal officials work jointly to inform the public about organ donation, organ transplantation, and brain death. Additionally, religious officials should donate organs by the way of example and, to increase their sensitivity, healthcare professionals should go more frequently to mosques and Mufti Stations. PMID- 26668847 TI - Empowerment, Leadership, and Sustainability in a Faith-Based Partnership to Improve Health. AB - Community-based participatory research is a noted approach for improving community health and reducing health disparities. Community partnerships can serve as a catalyst for change in public health efforts. This article will apply empowerment theory and sustainability principles to an existing faith-based partnership. BRANCH Out is a partnership among 13 African American churches, the City of Milwaukee Health Department - Community Nutrition, and the Medical College of Wisconsin. The partnership goal was to change inaccurate perceptions, knowledge and negative attitudes, and behaviors about chronic disease and promote healthy youth leadership. Faith-based empowerment can occur at the individual, organizational, and community level. BRANCH Out demonstrates how partnerships can be sustained in multiple ways. The partnership also highlights the unique contributions of churches to community health outcomes. PMID- 26668848 TI - Sexual function in women undergoing surgery for deep infiltrating endometriosis: a comparison with healthy women. AB - BACKGROUND: Endometriosis is a chronic and progressive condition of women of reproductive age. It is strongly associated with significant impairment of sexual function. AIM: To objectively evaluate the impact of laparoscopic excision of endometriosis on sexual function in patients with deep infiltrating endometriosis (DIE) compared to healthy women. SETTING AND DESIGN: Prospective study, including 250 patients with a diagnosis of DIE scheduled for laparoscopic surgery and 250 healthy women. METHODS: A sexual activity questionnaire, SHOW-Q (Sexual Health Outcomes in Women Questionnaire), was used to collect data pertaining to women's satisfaction, orgasm, desire and pelvic problem interference with sexual function. Women with DIE underwent complete excision of endometriotic lesions. All participants were asked to complete the SHOW-Q questionnaire before and after surgery. RESULTS: SHOW-Q scores in the endometriosis group before and 6 months after surgery were compared with the healthy group scores. A significant improvement was found between pre- and post-treatment in the scores of the satisfaction scale, desire scale and pelvic problem interference scale of SHOW-Q. The distribution of post-surgery SHOW-Q scores was comparable to healthy women's scores apart from the orgasm scale score, which was unchanged in the post-surgery group. CONCLUSIONS: The surgical approach to treatment has a positive impact not only on organ impairment but also on sexual function in women affected by DIE. PMID- 26668850 TI - Retracted: Effect of melatonin administration and long day-length on endocrine cycles in the hedgehog Erinaceus europaeus. PMID- 26668851 TI - The author replies:. PMID- 26668849 TI - Alcohol and Marijuana Use and Treatment Nonadherence Among Medically Vulnerable Youth. AB - BACKGROUND AND OBJECTIVE: Adolescents face peak risks for onset and intensification of alcohol and marijuana use. However, we know little about these behaviors and their associations with knowledge or treatment adherence among chronically ill youth, a medically vulnerable group. METHODS: Cross-sectional assessment of consented youth ages 9 to 18 years receiving care for asthma/cystic fibrosis, type 1 diabetes, arthritis, or inflammatory bowel disease (IBD) by using a self-administered online tool. Prevalence and correlates of risk behaviors and associations with knowledge and treatment adherence were estimated using descriptive statistics and logistic regression, controlling for demographics, mental health, and the multiclinic sampling frame. RESULTS: Of 403 consented youth (75.8% response), 51.6% were girls, 75.1% were white, and average age was 15.6 years. Of high school youth, 36.5% and 12.7% reported past-year alcohol use and binge drinking, respectively; 20% reported past-year marijuana use. Among high school youth, 53.1% and 37.2% answered correctly that alcohol can interfere with their medications and laboratory tests; youth answering incorrectly were 8.53 and 4.46 times more likely to drink and binge drink, respectively (P values , .001). Thirty-two percent and 8.3% of high school youth reported regularly forgetting or skipping their medications in the past 30 days; compared with past-year non drinking youth, drinkers were 1.79 and 1.61 times as likely to report regularly missing or skipping medications (P values , .05). CONCLUSIONS: Alcohol and marijuana use are common among youth with chronic medical conditions. Alcohol use is associated with treatment nonadherence. Education and preventive interventions are warranted to ameliorate risk. PMID- 26668852 TI - Retraction notice to "Benefits of different urea supplementation methods on the production performances of Merino sheep" [The Veterinary Journal 200 (2014) 398 403]. PMID- 26668853 TI - Response. PMID- 26668854 TI - Response. PMID- 26668855 TI - Response. PMID- 26668856 TI - Response. PMID- 26668857 TI - Authors' reply. PMID- 26668858 TI - Editorial comment. PMID- 26668859 TI - An unusual cause of ascites. PMID- 26668860 TI - Acute parvovirus B19 infection detected in bone marrow biopsy. PMID- 26668861 TI - Reply: To PMID 25495759. PMID- 26668863 TI - IRIDeS Fact Finding Mission to Nepal. PMID- 26668864 TI - Ebola Virus and Public Health (Part 2). Introduction. PMID- 26668862 TI - Giant gluteal lipoma presenting as a sciatic hernia. AB - BACKGROUND: Sciatic hernia is considered to be the rarest hernia of pelvic floor with less than one hundred reports published worldwide. Lipoma in the hernia sac is even more unique pathology with only few cases reported in the literature. We report a case of gluteal lipoma protruding into pelvis, displacing rectum with bladder and presenting as a sciatic hernia. CASE PRESENTATION: A 53-year-old male presented with an expanding, slightly reducible, right gluteal painful mass, back pain, dull pressure in lower abdomen and perianal region radiating to the right buttock, urgent urination and defecation. Lower back pain lasts for more than 7 years, other symptoms-6 months. No spinal pathology was found on X-ray. On examination patient seemed well nourished, BMI 29, abdomen was soft, without palpable masses or signs of peritonitis. Digital rectal examination showed no pathology. There was a reducible lump on the lateral side of right gluteus. Computer tomography (CT scan) demonstrated a large intra- and extra-pelvic fatty mass traversing the greater sciatic foramen. The tumor was surgically removed through lower middle laparotomy approach. Subsequent pathological examination revealed lipoma. The patient recovered uneventfully, was discharged 8 days later. MRI scan was advised following 1 year after the surgery. CONCLUSION: The presence of a gluteal mass should always suggest the possibility of a sciatic hernia. PMID- 26668865 TI - [One must let creative men grow]. PMID- 26668866 TI - [Doctors in the eternal ice]. PMID- 26668868 TI - ANMF pledges support to nurse practitioners. PMID- 26668867 TI - [Personalities in the history of medicine. Alfred Neisser]. PMID- 26668869 TI - ANMF leads fight to protect paid parental leave. PMID- 26668871 TI - The right to die. PMID- 26668870 TI - National health program for substance use. PMID- 26668872 TI - Chronic disease costs complex. PMID- 26668873 TI - Hasty decisions cause missed injuries. PMID- 26668874 TI - Concerns new emergency healthcare role sells out NPs. PMID- 26668875 TI - Queensland's push to strengthen forensic nursing workforce. PMID- 26668876 TI - Call for elder abuse units. PMID- 26668877 TI - Why location and context matter in forensic nursing--a Victorian perspective. PMID- 26668878 TI - Victorian forensic mental health bed crisis. PMID- 26668879 TI - Paying it forward from the bedside to the screen. PMID- 26668880 TI - School nurses essential in solving child health crisis. PMID- 26668881 TI - Research set to help prevent lifestyle-related diseases. PMID- 26668882 TI - Graduate nurses struggle to enter the sector. PMID- 26668883 TI - Winning the war against Ebola. PMID- 26668884 TI - Chlamydia screening can prevent harm to newborns. PMID- 26668885 TI - Aboriginal communities have world's highest dementia rate. PMID- 26668886 TI - Model Systems for Understanding Mechanisms of Nongenotoxic Carcinogenesis: Response. PMID- 26668887 TI - CMS Takes the Lead In Oncology Payment Reform. PMID- 26668888 TI - Maternity discrimination. PMID- 26668889 TI - Randomised controlled trial of self-hypnosis for intrapartum pain. PMID- 26668890 TI - The birth CONTINUUM. WHERE DOES NORMALITY SIT? PMID- 26668891 TI - Investing in services to members. PMID- 26668892 TI - Piloting revalidation. PMID- 26668893 TI - FEAR among midwives. PMID- 26668894 TI - Saturation point. PMID- 26668895 TI - A bug's life. PMID- 26668896 TI - The Diabetes-Depression Connection. PMID- 26668898 TI - Going low. This is your brain on hypoglycemia. PMID- 26668897 TI - betaSigmaTauLambda testing. PMID- 26668899 TI - Supermarket Smarts: Yogurt. PMID- 26668900 TI - Supermarket Smarts: Nutrition Bars. PMID- 26668902 TI - World War I Lemnos nurses memorial. PMID- 26668901 TI - Supermarket Smarts: Nondairy Milk. PMID- 26668903 TI - Nurse researcher in Australia's top 10. PMID- 26668904 TI - Penalty shootout looms as slashing of rates begins. PMID- 26668905 TI - Jobless rise worrying trend. PMID- 26668906 TI - HESTA first for Indigenous reconciliation. PMID- 26668907 TI - Flying start for two country students. PMID- 26668908 TI - Reducing the burden of non-communicable diseases. PMID- 26668909 TI - The missing links in patient care. PMID- 26668910 TI - ANMF Vic Branch land knockout High Court decision. PMID- 26668911 TI - Registered nurses essential in aged care, NSW inquiry told. PMID- 26668912 TI - Rally against China Free Trade Agreement. PMID- 26668913 TI - Inquiry into paid parental leave moves ahead. PMID- 26668914 TI - Lymphoplasmacytic lymphoma with prominent mast cell infiltrates. PMID- 26668915 TI - Adult T-cell leukemia/lymphoma. PMID- 26668916 TI - [Trends in occurrence, treatment, and outcomes of acute myocardial infarction in Tuscany Region (Central Italy), 1997-2010]. AB - OBJECTIVES: to describe trends in attack rate, treatment, and outcomes of acute myocardial infarction (AMI) in Tuscany Region (Central Italy). DESIGN: population based epidemiological study using the Tuscany Acute Myocardial Infarction Registry. SETTING AND PARTICIPANTS: cases have been identified by record linkage between the hospital discharge database and the mortality registry, and divided into hospitalised AMI (1997-2012) and out-of-hospital coronary deaths (1997 2010). Details on hospitalised cases based on the presence/absence of ST-segment elevation (STEMI / NSTEMI) can be detected for the period 2001-2012. MAIN OUTCOMEMEASURES: distribution by calendar time, gender, and type of event of absolute frequencies, age-standardised attack rates (per 100,000; standard Tuscany population, 2001) and percentages (standard: total hospitalised cases in 2011) of invasive cardiac procedures and 28-day case fatality in hospitalised cases. RESULTS: a reduction in both out-of-hospital coronary deaths and STEMI hospitalisations (attack rates, respectively, - 2.3% and -3.9% in males, -3.3% and -4.1% in females) and an increase in NSTEMI hospitalisations (+13.1% in males and +13.3% in females) were shown. The use of invasive cardiac procedures (PCI, coronary angiography) in hospitalised cases shows a considerable increase over time both in STEMI and in NSTEMI. The proportion, however, always remains lower in the whole period after the age of 70 and in women. The short term prognosis in hospitalised AMI cases shows an improvement over time, which, however, disappears when stratified by type of AMI. This trend is mainly related to the different weight that STEMI and NSTEMI have on incidence over time (increase in attack rates for NSTEMI and reduction for STEMI, with worst prognosis). CONCLUSIONS: results confirm the important changes in epidemiology, clinical presentation, and treatment of acute coronary disease in Tuscany, previously identified in the international literature. Differences in coronary reperfusion treatment of hospitalised cases still persist by age and gender. Additional efforts are needed to ensure equity in access to the best treatment for AMI. PMID- 26668917 TI - [Childhood cancer incidence in Apulia Region (Southern Italy), 2003-2008]. AB - OBJECTIVES: to investigate, for the first time, the incidence rates of malignant childhood cancers (children aged 0-14 years) in Apulia Region (Southern Italy) in the period 2003-2008. DESIGN: to compute incidence rates of childhood cancers from Apulia Region Cancer Registry database compared with the corresponding results published in 2012 by the Italian cancer registries network (AIRTUM),where data from the Apulia population were not included, because not available. SETTING AND PARTICIPANTS: we selected all incident cases of malignant tumours (behaviour: /3 of ICD-O-3 classification) in children aged 0-14 registered in the Apulia cancer registry. Local health unit (LHU) of Lecce (section of the Apulia cancer registry) collected data from 2003 to 2006; LHU of Taranto, BT, and Brindisi collected data from 2006 to 2008. MAIN OUTCOME MEASURES: we computed crude, age specific, and directly standardised rates (DSR), with 95% confidence intervals, of all malignant tumours, all categories and 5 subgroups of the ICCC-3 classification; standardised incidence ratios (SIR) for all childhood malignant tumours using the rates of the AIRTUM Pool 2003-2008 as reference . RESULTS: incident cases were 183. DSR (x106) of all childhood malignant tumours are: Apulia Region 169.7 (95%CI 145.9- 196.4); Brindisi 160.4 (95%CI 106.2-232.9); BT 177.7 (95%CI 122.7-248.7); Lecce 144.3 (95%CI 111.1-184.2); Taranto 216.2 (95%CI 163.0-281.4). SIR estimates are: Apulia Region 102.9 (95%CI 88.5-119.0); Brindisi 100.2 (95%CI 66.6-144.9); BT 105.4 (95%CI 73.0-147.2); Lecce 85.5 (95%CI 66.0 109.0); Taranto 134.6 (95%CI 101.7-174.8). Main incidence measures for all ICCC-3 categories and five subgroups of childhood cancers in Apulia are also reported. CONCLUSIONS: in Apulia Region, we estimated a DSR for all childhood malignant tumours very close to that of the AIRTUM Pool. DSRs for each ICCC-3 category look comparable with the data from the national survey too. When data of each LHU were analysed, the SIR estimate makes it evident an excess of all malignant childhood cancers in the LHU of Taranto. Other results of particular cancers and specific age groups also provide suggestions for further investigations. PMID- 26668918 TI - [Confirmation of an excess of cancer mortality in a cohort of workers of a chromium thin-layer plating]. AB - OBJECTIVES: to extend up to year 2013 the follow-up for mortality of a cohort of workers in a chromium and nickel plating plant, where an excess of lung cancers was already identified. DESIGN: 10 years after the first study about cancer mortality in a cohort of workers involved in the chromium thin-layer plating, published in 2006, we updated the evaluation of themortality of a cohort ofworkers employed in the same chromiumthin-layer plating factory with at least 6 months of work between 1968 and 1994.The mortality rates are compared with those of the Italian and Veneto Region (Northern Italy) populations.The dose-response relationship between work duration and lung cancer is assessed by adjusted Poisson regression. SETTING AND PARTICIPANTS: 127 unskilled or skilled workers involved in the production process. RESULTS: in the updated follow-up, 35 deaths occurred among the subjects under study: 19 for cancer (of which 11 for lung cancer and 3 for pancreatic cancer). A marked excess ofmortality due to lung cancer is observed. In addition, the newfollowup shows a significant excess of pancreatic cancer mortality. Lung cancer mortality is positively associated with work duration and the risk increases by 13%(95%CI 1-26) for each additional year of work. CONCLUSIONS: the extension of followup confirms that this cohort expresses an increased mortality from cancer deaths, due to a marked excess of lung and pancreatic cancers. The effect of smoking has only a secondary effect in the cancer onset expressed by this cohort. The risk of lung cancer increased with work duration and thus with occupational exposure to chromium and nickel. PMID- 26668919 TI - [Reducing non-communicable diseases and health care costs: building a prevention alliance]. AB - In Italy, as well as in most European Countries, the loss of almost 70% of the years of life is attributable to cerebro-cardiovascular diseases and cancers. Whereas the Italian population is expected to grow older, with a significant increase in the burden of chronic non-communicable diseases, the reduction in incidence of chronic diseases and the compression of morbidity are priorities. This is the reason why in Italy the implementation of the National Plan for Prevention and related regional plans becomes necessary, as it can promote the co operation of multidisciplinary skills in several areas: political, health, economic, legal, sociological. In Piedmont (Northern Italy), it seems useful the creation of a regional Laboratory of prevention,which provides support for the development and implementation of the regional prevention plan, through actions and programmes based on cost-effectiveness analyses. The use of resources in prevention should not be exclusively interpreted as a cost, but as an investment, which, in some cases, can become an avoided cost. Using prevention policies makes it possible to gain years of healthy life and to potentially reduce the cost of healthcare system. The creation of the Laboratory of prevention is a multidisciplinary context, so it is an opportunity to involve the stakeholders in order to achieve the regional health objectives. PMID- 26668920 TI - [Economic difficulties keep on influencing early diagnosis of colorectal cancer]. PMID- 26668921 TI - [Leonard Defrance and occupational health in 18th century art]. PMID- 26668922 TI - [Analysis of psychological distress between the paediatric population immigrant and resident in a Local Health Unit of Milan Province (Northern Italy)]. AB - OBJECTIVES: to figure out if there are differences in access to psychiatric services between Italian and immigrant paediatric populations. DESIGN: we analysed the data of the year 2012 from the Banca dati del disagio psichico, a database on psychological distress created by the Epidemiological Unit of the Local Health Unit Milan 1 (Lombardy, Northern Italy). The database is based on a data warehouse system that integrates health and social data, and gives the opportunity to calculate the prevalence rates of the main clusters of psychiatric diseases according to ICD-10 categories. SETTING AND PARTICIPANTS: the sample includes 162,197 residents younger than 18 years (minors), divided into 4 subgroups depending on the place of birth (Italy or abroad) and citizenship (Italian or foreign). MAIN OUTCOME MEASURES: we calculated the standardised treated prevalence of the 11 clusters of mental diseases in the 4 subgroups and evaluated the Standardised Prevalence Ratio (SPR) and their confidence intervals using as reference the Italian paediatric population with Italian citizenship. RESULTS: in 2012, 7.2%minors were diagnosed a mental illness or accessed mental health services or were prescribed psychotropic medicines. We found the lowest SPRs of psychiatric illnesses in immigrants (0.91 born in Italy; 0.74 born abroad) and the higher in Italians born in foreign Countries (1.34). In particular, migrant minors born in Italy have lower SPR of developmental disorders (0.84) and behaviour and emotional disorders (0.68), but higher SPR of mental retardation (1.52) and anxiety disorders (1.36). Migrant minors born abroad have lower SPR of developmental disorders (0.52), but higher rates of mental retardation (1.30). Italians born in foreign Countries show a SPR for personality disorders and mental retardation of 4.86 and 2.02, respectively. CONCLUSIONS: immigrant minors have a lower prevalence of psychiatric diseases than Italian minors; however, Italians born in foreign Countries show a higher prevalence of psychiatric disorders. PMID- 26668923 TI - [EDITORIAL]. PMID- 26668924 TI - [Klaus Conrad: incipient schizophrenia]. PMID- 26668925 TI - [Body excesses. Fictions of transmission and disease in Latin America]. PMID- 26668927 TI - Somebody's Watching Me. PMID- 26668928 TI - Researchers Successfully Create Synthetic Materials Rivaling Hardness of Teeth. PMID- 26668926 TI - SUPERMARKET SMARTS. Coffee Creamers. PMID- 26668930 TI - Dentist's Work Shows Promise in Helping Patients With Parkinson's. PMID- 26668929 TI - Alleviating Workday Pain. PMID- 26668931 TI - Sitting...Ugh! Researchers All Agree: Stand Up for Good Health! PMID- 26668932 TI - A Molecular Approach to Well-defined Metal Sites Supported on Oxides with Oxidation State and Nuclearity Control. AB - A molecular understanding of the catalytically active site is essential to rationally develop metal-containing heterogeneous catalysts. The controlled grafting of molecular precursors on pre-treated supports, often referred to as surface organometallic chemistry, is an approach to prepare well-defined heterogeneous catalysts with complex organic functionalities. However, many heterogeneous catalysts do not contain organic ligands coordinated to their active sites. To model such sites, the principles of surface organometallic chemistry therefore have to be adapted. Here, we describe a method, which provides access to molecularly-defined metal sites supported on oxides, which do not contain organic functionalities and are uniform in oxidation state and nuclearity. By consecutive grafting of suitable molecular precursors and controlled thermal treatment, we prepared and characterized well-defined dinuclear Cr(II) and Cr(III) species and mononuclear Cr(III) species supported on silica. We also investigated the polymerization activity of these materials in view of the well-known ethylene polymerization catalyst based on CrO(x)/SiO2, the so-called Phillips catalyst. This study led to new insights on the catalytically active sites in ethylene polymerization, which are based on Cr(III), not Cr(II). PMID- 26668933 TI - Instrumentino: An Open-Source Software for Scientific Instruments. AB - Scientists often need to build dedicated computer-controlled experimental systems. For this purpose, it is becoming common to employ open-source microcontroller platforms, such as the Arduino. These boards and associated integrated software development environments provide affordable yet powerful solutions for the implementation of hardware control of transducers and acquisition of signals from detectors and sensors. It is, however, a challenge to write programs that allow interactive use of such arrangements from a personal computer. This task is particularly complex if some of the included hardware components are connected directly to the computer and not via the microcontroller. A graphical user interface framework, Instrumentino, was therefore developed to allow the creation of control programs for complex systems with minimal programming effort. By writing a single code file, a powerful custom user interface is generated, which enables the automatic running of elaborate operation sequences and observation of acquired experimental data in real time. The framework, which is written in Python, allows extension by users, and is made available as an open source project. PMID- 26668934 TI - Lightening up Ruthenium Complexes to Fight Cancer? AB - In medicine, light is used in a medical treatment called photodynamic therapy (PDT) to treat some types of cancer and skin diseases. This technique generally allows for reduced side effects compared to traditional chemotherapy. However, PDT is not fully effective on hypoxic tumors (i.e. lacking oxygen). To overcome this important drawback, photoactivated chemotherapy (PACT) agents have been designed to obtain light-mediated cancer cell death via an oxygen-independent mechanism. Ruthenium complexes have already been and are currently deeply explored as traditional anticancer agents. However, as reported in this short review article, such compounds can also bring novel opportunities in the field of light-mediated cancer treatment. Herein, we report on our findings in the optimization of Ru(II) polypyridyl complexes as PDT and PACT agents for the potential treatment of cancer and, interestingly, also of bacterial infections. PMID- 26668935 TI - Enantioselective Rhodium-catalyzed C-C Bond Activation of Cyclobutanones. AB - The activation of carbon-carbon bonds has attracted much attention in the past decade. Despite important progress, the development of asymmetric reactions lags behind. For the first time, asymmetric rhodium(I)-catalyzed direct oxidative additions into enantiotopic C-C bonds of cyclobutanones could be realized. Subsequent carboacylation of tethered olefins and carbonyl groups of the generated rhoda(III)cyclopentanone give an efficient access to complex polycyclic scaffolds in high yields. Despite operating at high reaction temperatures, the processes are characterized by outstanding enantioselectivities of generally greater than 99.5:0.5 er. PMID- 26668936 TI - Functionalised Clathrochelate Complexes--New Building Blocks for Supramolecular Structures. AB - Tris(dioxime) iron(II) clathrochelate complexes functionalised with 3- and 4 pyridyl groups have been employed as building blocks in the preparation of supramolecular structures by coordination-driven self-assembly. These complexes possess a number of desirable characteristics, being straightforward to synthesise and offering ample opportunity for steric and functional modification. Clathrochelate-based 4,4'-bipyridyl metalloligands from 1.5 nm to 5.4 nm in length were prepared in up to two steps and their potential as building blocks for supramolecular architectures demonstrated through the preparation of a discrete molecular square and a three dimensional (3D) coordination polymer. Furthermore, the structure-directing capability of clathrochelate building blocks was illustrated through the synthesis of octahedral cage compounds, which are capable of encapsulating the large, hydrophobic BPh4- anion in aqueous solvent mixtures. PMID- 26668937 TI - Potassium Sensitive Optical Nanosensors Containing Voltage Sensitive Dyes. AB - lonophore-based ion-selective optical nanosensors have been explored for a number of years. Voltage sensitive dyes (VSDs) have been introduced into this type of sensors only very recently, forming a new class of analytical tools. Here, K(+) sensitive nanospheres incorporating a lipophilic VSD were successfully fabricated and characterized. The nanosensors were readily delivered into the social amoeba Dictyostelium discoideum in a non-invasive manner, forming a promising new platform for intracellular ion quantification and imaging. PMID- 26668938 TI - Integrated One-Pot Synthesis of 1,3-Oxazinan-2-ones from Isocyanoacetates and Phenyl Vinyl Selenones. AB - Bronsted base (Et3N or DBU) catalyzed Michael addition of alpha-substituted alpha isocyanoacetates to phenyl vinyl selenones followed by a Bronsted acid (PTSA) catalyzed domino oxidative cyclization afforded 1,3-oxazinan-2-ones in good to excellent yields. Enantio-enriched 1,3-oxazinan-2-ones were accessible using a Cinchona alkaloid-derived bifunctional catalyst for the first step. In this integrated one-pot process, the pheny selenonyl group acted consecutively as an activator, a leaving group and a latent oxidant. PMID- 26668939 TI - Thin Layer Samples Controlled by Dynamic Electrochemistry. AB - We summarize here recent advancements on thin layer samples controlled by dynamic electrochemistry techniques for determining different ions that include potassium, calcium, protamine, nitrate, nitrite and halides in diverse environmental and clinical samples. Generally, a thin layer liquid (less than 100 MUm in thickness) is confined between a working electrode and an ion-selective membrane. Once an external electrical perturbation (i.e. constant potential) is applied to the system, an exhaustive ion transfer process is imposed in the entire thin layer solution. As a result, the observed charge (integration of the current decay) is proportional to the depleted ion concentration. Other electrochemical protocols such as linear sweep voltammetry were also explored aiming at the discrimination of several ions presented in the thin layer. One of the most attractive examples involves the detection of a mixture of three halides (iodide, bromide and chloride), which can be well resolved at moderated scan rates (10 mV.s(-1)). Paper-based coulometric sensing on thin layers defined by cellulose papers are being developed in view of translating these new concepts into a reliable and low cost sensing platform. PMID- 26668940 TI - Mimicking the in vivo Environment--The Effect of Crowding on RNA and Biomacromolecular Folding and Activity. AB - In vitro studies on macromolecules, like proteins and nucleic acids, are mostly carried out in highly diluted systems where the molecules are studied under artificial conditions. These experimental conditions are optimized for both the system under investigation and the technique used. However, these conditions often do not reflect the in vivo situation and are therefore inappropriate for a reliable prediction of the native behavior of the molecules and their interactions under in vivo conditions. The intracellular environment is packed with cosolutes (macromolecules, metabolites, etc.) that create 'macromolecular crowding'. The addition of natural or synthetic macromolecules to the sample solution enables crowding to be mimicked. In this surrounding most of the studied biomolecules show a more compact structure, an increased activity, and a decrease of salt requirement for structure formation and function. Herein, we refer to a collection of examples for proteins and nucleic acids and their interactions in crowding environments and present in detail the effect of cosolutes on RNA folding and activity using a group II intron ribozyme as an example. PMID- 26668941 TI - Forbidden Vibrational Transitions in Cold Molecular Ions: Experimental Observation and Potential Applications. AB - A range of interesting fundamental scientific questions can be addressed by high precision molecular spectroscopy. A promising way towards this goal is the measurement of dipole-forbidden vibrational transitions in molecular ions. We have recently reported the first such observation in a molecular ion. Here, we give an overview of our method and our results as well as an outlook on potential future applications. PMID- 26668942 TI - Scalable Synthesis of Two-dimensional Polymer Crystals and Exfoliation into Nanometer-thin Sheets. AB - Two-dimensional materials have moved into the spotlight of researchers. The isolation of single graphene sheets has shown that restricted dimensionality can lead to interesting properties. Bottom-up synthesis of organic, covalently-bonded structures is, however, still challenging. In this publication we give a synopsis of a recently published monomer that is easily accessible and reversibly provides chiral two-dimensional polymer single crystals, which can be exfoliated into nanometer-thin sheets and show promise for applications in, for example, nonlinear optics and ultrathin membranes. PMID- 26668943 TI - WO3/CeO2/TiO2 Catalysts for Selective Catalytic Reduction of NO(x) by NH3: Effect of the Synthesis Method. AB - WO3/CeO2/TiO2, CeO2/TiO2 and WO3/TiO2 catalysts were prepared by wet impregnation. CeO2/TiO2 and WO3/TiO2 showed activity towards the selective catalytic reduction (SCR) of NO(x) by NH3, which was significantly improved by subsequent impregnation of CeO/TiO2 with WO3. Catalytic performance, NH3 oxidation and NH3 temperature programmed desorption of wet-impregnated WO3/CeO2/TiO2 were compared to those of a flame-made counterpart. The flame-made catalyst exhibits a peculiar arrangement of W-Ce-Ti-oxides that makes it very active for NH3-SCR. Catalysts prepared by wet impregnation with the aim to mimic the structure of the flame-made catalyst were not able to fully reproduce its activity. The differences in the catalytic performance between the investigated catalysts were related to their structural properties and the different interaction of the catalyst components. PMID- 26668944 TI - The Effect of the Electronic Nature of Spectator Ligands in the C-H Bond Activation of Ethylene by Cr(III) Silicates: An ab initio Study. AB - The Phillips catalyst, chromium oxides supported on silica, is one of the most widely used catalysts for the industrial production of polyethylene (PE). We recently synthesized a well-defined mononuclear Cr(III) silicate as active site model of the Phillips catalyst. The catalytic activity of this well-defined catalyst was similar to the industrial Phillips catalyst. We proposed that C-H bond activation of ethylene over a Cr-O bond initiates polymerization in this Cr(III) catalyst. Our results also showed that the presence of a second ethylene olefin in the coordination sphere of Cr decreases the intrinsic energy barrier of the C-H activation of ethylene. In order to understand the effect of this additional ligand in the C-H activation of ethylene by the Cr(III) catalyst, we evaluated the energetics of this step with different spectator ligands (C2H4, C2F4, N2 and CO) coordinated to the Cr center. The Charge Decomposition Analysis (CDA) of the bonding interactions between the Cr(III) catalyst and the ligands showed that the intrinsic energy barrier for the C-H activation of ethylene decreases with the increasing electron-donor properties of the spectator ligand. PMID- 26668982 TI - In Memoriam: Kanu Chatterjee, MD (1934-2015). PMID- 26668983 TI - This letter was sent to Dr. Hala Agha, who responds as follows. PMID- 26668984 TI - SMALL INTESTINAL TUMORS. AB - Small intestine is the longest part of the gastrointestinal tract. It represents 75% of its length and 90% of the mucosal surface. Benign tumors are observed at 3 6% and the malignant--1-3% of all cancers of all GI malignancies. PATIENTS AND RESULTS: 23 patients with small intestinal tumors between 2001 and 2014 were admitted in Second Department of surgery. They were comparable in age, location and tumor characteristics. The reasons for hospitalization of patients were following symptoms: bowel obstruction, abdominal pain, GI bleeding, anemia. The diagnosis was established on the clinical presentation, performance status and imaging procedures (CT and MRI). The histological types of the tumor were adenocarcinoma--56.5%, GIST--17.4%, sarcoma--9.3% NET--8.7%, and lymphoma--8.1%. Surgical treatment was performed in all patients and included tumor resection, followed by side-to-side or end-to-end anastomosis. CONCLUSION: Small intestinal tumors are characterized by a low frequency. Diagnosis is made in advanced stage of disease because of lack of symptoms and difficult determination of the clinical presentation. Surgery is the only method that allows radical treatment. Chemotherapy is recommended in patients with malignant small bowel tumors. PMID- 26668985 TI - CIRCULAR EXCISION AND "PURSE-STRING" TECHNIQUE IN SURGICAL TREATMENT OF HEMANGIOMAS. AB - Hemangiomas are the most common benign vascular lesions in childhood. Surgical removal of hemangiomas in childhood is usually delayed till intralesional blood flow spontaneously decreases, but the fibroadipose tissue and atrophic skin remain even after general involution. The aim of our study is to provide such a technique and method that can redistribute the tension around the defect after the excision and achieve complete and simple closure. METHODS AND MATERIALS: Six children with hemangiomas of different size and location on the face underwent circular excision of the defects and subsequent closure using the "purse-string" method. RESULTS: All skin defects were completely closed without subsequent complications requiring reoperations. No deformation occurred in the nearby tissues and the final aesthetic appearance of the scar was excellent. CONCLUSION: Circular excision combined with a "purse-string" technique is an effective method of achieving complete closure of the skin defect with excellent results. PMID- 26668986 TI - LAPAROSCOPIC TREATMENT OF RECTAL CANCER. AB - There is an established standard for the surgical treatment of rectal neoplasms. Every conventional operation can be performed by means of laparoscopy, if the complex approach to the disease and classical oncological principles are observed. Depending on the height of tumor, surgical operations, different in tactical and technical terms, are performed. The correct preoperative staging, planning, and securing of resources guarantee the favorable outcome of therapy. The main advantages are the less postoperative pain and briefer hospital stay. The better visualization of pelvic organs and routine use of high-energy sources reduce the blood loss and potential complications. With a view to ensure modern treatment of this major group of patients, the input of the required resources, for turning into one of the routine methods of rectal cancer treatment, is a necessity. ABBREVIATIONS USED: LAR (laparoscopic anterior resection), LLAR (low laparoscopic anterior resection), LIsRR (laparoscopic intersphincteric resection of the rectum), TME (total mesorectal excision), TATME (transanal total mesorectal excision), LER (laparoscopic extirpation of the rectum), IMA (inferior mesenteric artery), and IMV (inferior mesenteric vein). PMID- 26668987 TI - ENDOVASCULAR TREATMENT OF AN ANEURYSM OF THE SPLENIC ARTERY. AB - Aneurysms of the splenic artery account for about 60% of all aneurysms of visceral arteries. Most of them are asymptomatic until rupture and are discovered accidentally, usually after an imaging study. The treatment is surgical or endovascular depending on the type, location and size. We present a case of a patient with an asymptomatic, accidentally found aneurysm of the splenic artery which we successfully treated with a covered stent. The control CT-angiography on 6th month showed patent stent and totally occluded aneurysm. It is very important in cases of acute abdomen and hemorrhagic shock to think of a ruptured aneurysm. In these cases the treatment of choice is endovascular as it is mini-invasive and organ-saving. PMID- 26668988 TI - PRINCIPLES, METHODS AND ALGORITHM BEHAVIOR IN THE TREATMENT OF COMPLICATED LEFT SIDED COLORECTAL CANCER. AB - Colorectal cancer (CRC) is a widespread disease and represents an extremely important social--health problem caused by its increasing frequency in recent years, incl. our country. The current high level of development of medical science, oncology and surgery and achieved significant results in the treatment of colorectal cancer, there are still a number of unresolved problems--high morbidity and mortality, higher rates of complicated forms and frequent recurrences, as well as the absence of clear and accurate prognostic criteria defining an exact individual therapeutic and surgical conduct for each patient. PMID- 26668989 TI - [Current status and prospect of translational medicine in nanotechnology]. AB - Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge. PMID- 26668990 TI - [Pain of high-throughput screening--pan assay interference compounds]. AB - High-throughput screening is a regular approach available for identitying new lead compounds for the growing validated drug targets in drug screening. However, it has also introduced a large number of peculiar molecules which interfere drug screening. Pan assay interference compounds (PAINS) interfere with the progress of drug screening in various ways, such as interfering with a biochemical assay, modifying the protein, aggregate-based inhibitors and so on. So it is of vital significance to remove them. This paper has consulted the concept, category of PAINS and reviewed the way of PAINS interfering and the countermeasures to cope with them to direct the approach of high through screening and improve the hits percent. PMID- 26668991 TI - [Research progress of small peptidomimetics]. AB - The study of peptide drugs has been an important direction in research and development of new drugs. However, lots of natural macromolecular peptides are limited in clinical use by their metabolic instability and low bioavailability. In recent years, the active small peptidomimetics open up a new hotspot of peptide drug development with the characteristics of low molecular weight, high bioactivity and structural modification. Many peptidomimetics are on the market or on the clinical study. This paper elaborated the small peptidomimetics approved by American Food and Drug Administration (FDA) from 2005 to 2014, and reviewed their researching status with source, synthetic method, chemical structure, marketing time, indication, clinical efficacy and safety. Research prospects in this field were discussed. PMID- 26668992 TI - [The role of heat shock protein 70 in regulating neuroinflammation]. AB - Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease. PMID- 26668993 TI - [Advances in diabetic animal models and its application in the traditional Chinese medicine research]. AB - The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine. PMID- 26668994 TI - [Progress in the biomarker discovery for drug-induced liver injury]. AB - The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI. PMID- 26668995 TI - [Antiviral effects of the combination of glycyrrhizin and ribavirin against influenza A H1N1 virus infection in vivo]. AB - Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg . kg(-1) . d(-1) glycyrrhizin and 40 mg . kg(-1) . d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-alpha (P < 0.01) and IL-1beta (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents. PMID- 26668996 TI - [The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory]. AB - The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4 induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1beta (IL-1beta) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB 1, tumor necrosis factor-alpha (TNF-alpha) and IL-1beta (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-alpha and IL-1beta as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury. PMID- 26668997 TI - [Photothermal effects of metallic carbon nanotubes on human breast cancer cells]. AB - SWNTs are a mixture of 1/3 metallic SWNTs (m-SWNTs) and 2/3 semiconducting SWNTs (s-SWNTs). It is desirable to separate the metallic SWNTs from the semi conducting ones. In this study m-SWNTs was separated by using a poly[(m phenylenevinylene)-alt-(p-phenylenevinylene)] (PmPV) derivative and used as photo thermal media instead of SWNTs. The separation effects of m-SWNTs were evaluated by Raman spectra, molecular modeling and TEM images. The effects of m-SWNTs on MCF-7 cell proliferation and apoptosis were evaluated with MTT assay and flow cytometry, respectively. m-SWNTs were separated with high purity. A strong inhibition of MCF-7 cell growth was observed with the m-SWNTs under near-infrared (NIR) light irradiation. Our results will be helpful for the potential applications of m-SWNTs in clinical photothermal cancer therapy. PMID- 26668998 TI - [Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation]. AB - The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1beta, IL-6, IL-8 and TGF-beta1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKalpha phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP 1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1beta, IL-6, IL-8 and TGF-beta1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue. PMID- 26668999 TI - [The mechanisms of heparin-derived oligosaccharide on the inhibition of smooth muscle cells proliferation induced by platelet-derived growth factor]. AB - In this study, the effect of heparin-derived oligosaccharide (HDO) on platelet derived growth factor (PDGF) induced vascular smooth muscle cells (VSMCs) proliferation and the related signal transduction mechanisms were investigated. MTT assays were used to measure VSMCs proliferation. Cell cycle distribution was analyzed by flow cytometry. The level of key regulatory proteins in PKC, MAPK and Akt/PI3K pathways were determined by RT-PCR, Western blot and immunocytochemical methods. Meanwhile, mRNA expressions of some proto-oncogenes were assayed by RT PCR method. Our data showed that HDO (0.01, 0.1 and 1 MUmol . L(-1)) inhibited 30 ng . mL(-1) PDGF-induced VSMCs proliferation in a dose-dependent manner, blocked the G1/S transition and inhibited the level of key regulatory proteins and some proto-oncogenes (P < 0.05). The results showed that HDO may decrease the key regulatory proteins expression, hence suppress the transcription of proto oncogene and G1/S transition, finally inhibiting VSMCs proliferation. PMID- 26669000 TI - [Sodium nitrite reduces lipid accumulation in steatotic cells by enhancing autophagy]. AB - Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes and nitrite treatment reduces total triglyceride levels in the high-fat diet mice. Therefore, the present study aimed to determine the effects of nitrite on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L-02 cells were induced by incubating L-02 cells with 1.2 mmol . L(-1) oleic acid (OA) for 24 h. Secondly, steatotic L-02 cells were treated with 0.2 mmol . L(-1) sodium nitrite (SN) plus 3-methyladenine (3 MA), or chloroquine (CQ) for 24 h, and then lipid accumulation was measured with oil red O staining and triglyceride quantification. The notable steatosis could be observed in L-02 cells following exposure to 1.2 mmol . L(-1) OA for 24 h. Treatment with 0.2 mmol . L(-1) sodium nitrite reduced lipid accumulation in steatotic L-02 cells. 3-MA weakened the ability of sodium nitrite to ameliorate hepatic steatosis. Additionally, the sodium nitrite increased number of LC3-II immunostaining puncta and LC3-II protein expression was confirmed by immunofluorescence or Western blot analysis, and the effects were enhanced by CQ treatment. The number of increased cytoplasm vacuoles and lysosomes increased was confirmed by phase contrast and fluorescence microscope respectively. The increased autolysosome was detected by electron microscopy, this phenomenon could be reversed by CQ treatment. These data demonstrated that sodium nitrite enhanced the autophagic flux and decomposition of triglycerides in steatotic L-02 cells. PMID- 26669001 TI - [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives]. AB - To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine alpha, beta-unsaturated ketone) amine derivatives (5a 5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine alpha, beta-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID- 26669002 TI - [The synthesis of purine derivatives and its inhibitory activity on CD38 NADase]. AB - CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38. PMID- 26669003 TI - [Analysis of porphyrin photosensitizers using HPLC method]. AB - Photodynamic therapy (PDT), because of its good targeting, minimal invasion, and safety, is becoming a very active area in cancer prevention and treatment, in which the photosensitizers have proved to be the core element for PDT. We developed a new HPLC method for analyzing porphyrin photosensitizers using Shiseido Capcell PAK C18 (150 mm x 4.6 mm, 5 um) as the column at 30 degrees C, methanol-1% aqueous solution of acetic acid as the mobile phase in a flow rate of 1.0 mL . min(-1) in a gradient elution mode, and the detection wavelength at 380 nm. This method, showing good specificity, precision, accuracy and robusty via methodology validations, can be applied to the purity test and assay of porphyrin photosensitizers, and has played a key guide role in the R&D of the new porphyrin photosensitizer--sinoporphyrin sodium. PMID- 26669004 TI - [Identification of related substances in nicergoline by HPLC-MS]. AB - To study the related substances in nicergoline, electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of the related substances. Triple quadrupoles tandem MS/MS was employed for the determination of the fragmentations of the parent ions. 16 related substances were detected and identified to be eight synthetic by-products and eight degradation products, by using impurity references matching, product mass spectra fragmentations elucidation, and verified further according to synthetic processes and stress testing results. The results obtained are valuable for nicergoline manufacturing process control and quality assurance. PMID- 26669005 TI - [Discrimination of patients with Xiao-Chaihu Tang syndrome using 1H NMR metabonomics and partial least square analysis]. AB - 1H NMR metabonomics approach was used to reveal the chemical difference of urine between patients with Xiao-Chaihu Tang syndrome (XCHTS) and healthy participants (HP). The partial least square method was used to establish a model to distinguish the patients with Xiao-Chaihu-Tang syndrome from the healthy controls. Thirty-four endogenous metabolites were identified in the 1H NMR spectrum, and orthogonal partial least squares discriminant analysis showed the urine of patients with Xiao-Chaihu Tang syndrome and healthy participants could be separated clearly. It is indicated that the metabolic profiling of patients with Xiao-Chaihu Tang syndrome was changed obviously. Fifteen metabolites were found by S-pot of OPLS-DA and VIP value. The contents of leucine, formic acid, glycine, hippuric acid and uracil increased in the urine of patients, while threonine, 2-hydroxyisobutyrate, acetamide, 2-oxoglutarate, citric acid, dimethylamine, malonic acid, betaine, trimethylamine oxide, phenylacetyl glycine, and uridine decreased. These metabolites involve the intestinal microbial balance, energy metabolism and amino acid metabolism pathways, which is related with the major symptom of Xiao-Chaihu Tang syndrome. The patients with Xiao Chaihu Tang syndrome could be identified and predicted correctly using the established partial least squares model. This study could be served as the basis for the accurate diagnostic and reasonable administration of Xiao-Chaihu-Tang syndrome. PMID- 26669006 TI - [Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy]. AB - In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 +/- 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 +/- 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy. PMID- 26669007 TI - [Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles]. AB - The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg . mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved. PMID- 26669008 TI - Expression of ATP synthase CF1 alpha subunit gene (CTL-spn) as screened by the cDNA-SRAP approach is correlated with spininess in Carthamus tinctorius L. AB - The safflower floret is a traditional Chinese medicine used to promote blood circulation and remove obstruction in the channels. The spines on its bracts are considered a handicap when manual harvest is involved. In this study, cDNA-SRAP was used to systematically investigate which genes are associated with the spines. Sixty pairs of possible primer combinations were used on two cDNA pools representing spininess and spinelessness. Six transcript-derived fragments were identified, of which two with low recombination were sequenced successfully and named as GPY-1 and GPY-2. By using the RACE method, the full-length cDNA of GPY-2 is cloned and named as CTL-spn. The full-length cDNA of CTL-spn was 1 679 bp long with a 1 524 bp ORF encoding a 508 aminoacid protein. The deduced amino acid sequence of the CTL-spn gene shared a high homology (97%) with other known ATP synthase CF1 alpha subunits. Semiquantitative RT-PCR analysis revealed that the mRNA of GPY-1 and GPY-2 accumulated in only spiny lines. Considering the important role of ATP synthase CF1 alpha subunit in plants, it may directly take part in the formation process of spininess and enhancing resistance reaction of spiny safflower. Also, our results provide the important insights for breeding spineless cultivars of safflower. PMID- 26669010 TI - Preface. Diagnostic and Therapeutic Immunology. PMID- 26669009 TI - [Applylication of new type combined fragments: nrDNA ITS+ nad 1-intron 2 for identification of Dendrobium species of Fengdous]. AB - In this study, 17 kinds of Dendrobium species of Fengdous including 39 individuals were collected from 4 provinces. Mitochondrial gene sequences co I, nad 5, nad 1-intron 2 and chloroplast gene sequences rbcL, matK amd psbA-trnH were amplified from these materials, as well as nrDNA ITS. Furthermore, suitable sequences for identification of Dendrobium species of Fengdous were screened by K 2-P and P-distance. The results showed that during the mentioned 7 sequences, nrDNA ITS, nad 1-intron 2 and psbA-trnH which had a high degree of variability could be used to identify Dendrobium species of Fengdous. However, single fragment could not be used to distinguish D. moniliforme and D. huoshanense. Moreover, compared to other combined fragments, new type combined fragments nrDNA ITS+nad 1-intron 2 was more effective in identifying the original plants of Dendrobium species and could be used to identify D. huoshanense and D. moniliforme. Besides, according to the UPGMA tree constructed with nrDNA ITS+nad 1-intron 2, 3 inspected Dendrobium plants were identified as D. huoshanense, D. moniliforme and D. officinale, respectively. This study identified Dendrobium species of Fengdous by combined fragments nrDNA ITS+nad 1-intron 2 for the first time, which provided a more effective basis for identification of Dendrobium species. And this study will be helpful for regulating the market of Fengdous. PMID- 26669011 TI - Murine models of Aspergillosis: Role of collectins in host defense. AB - Aspergillus fumigatus, a ubiquitous fungus, causes a wide spectrum of clinical conditions ranging from allergic to invasive aspergillosis depending upon the hosts' immune status. Several animal models have been generated to mimic the human clinical conditions in allergic and invasive aspergillosis. The onset, duration and severity of the disease developed in models varied depending on the animal strain/fungal isolate, quantity and mode of administration of fungal antigens/spores, duration of the treatment, and type of immunosuppressive agent used. These models provide insight into host and pathogen factors and prove to be useful for evaluation of diagnostic markers and effective therapies. A series of studies established the protective role of collectins in murine models of Allergic Bronchopulmonary Aspergillosis and Invasive Pulmonary Aspergillosis. Collectins, namely surfactant protein A (SP-A), surfactant protein D (SP-D) and mannan binding lectin (MBL), are pattern recognition molecules regulating both innate and adaptive immune response against pathogens. In the present review, we discussed various murine models of allergic and invasive aspergillosis and the role of collectins in host defense against aspergillosis. PMID- 26669012 TI - Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE. AB - Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA. PMID- 26669013 TI - Association of estrogen receptor 1 (ESR1) haplotypes with risk for systemic lupus erythematosus among South Indians. AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving genetic, epigenetic and environmental factors and has higher incidence in women. In this study, we explored the association of estrogen receptor 1 (ESR1) rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms with susceptibility to SLE. PCR-RFLP and ELISA were used for genetic analysis and determination of specific autoantibodies, respectively. The univariate analysis showed no independent association of rs2234693 (OR: 1.14, 95% CI: 0.87 - 1.49, p = 0.36) and rs9340799 (OR: 0.87, 95% CI: 0.66-1.14, p = 0.34). The haplotype analysis using SHEsis platform revealed strong linkage disequilibrium between these two polymorphisms (D': 0.81, r2: 0.55). Among the four haplotype groups, the C-A haplotype (rs2234693-rs9340799) was strongly associated with the risk for SLE (OR: 2.10, 95% CI: 1.32 - 3.34, p = 0.001). The homozygous variant genotype of rs2234693 exhibited elevated TNF-alpha and depleted IFN-alpha, while the effects of rs9340799 were contradictory. The wild genotype of rs2234693 exhibited lower levels of IL-12 with number of rs9340799 variant alleles pronouncing this effect. From this study, it is concluded that the ESR1 haplotypes may influence the Th2 cytokine profile and susceptibility to SLE among the South Indians. PMID- 26669014 TI - Status of circulating immune complexes, IL8 titers and cryoglobulins in patients with dengue infection. AB - Dengue, a serious viral infection caused by the mosquito vector, Aedes aegyptii, affects about 390 million people annually from more than 125 countries across the globe. However, until now, there is no reliable clinical or laboratory indicator to accurately predict the development of dengue severity. Here, we explored critical pathophysiological determinants like IL8, circulating immune complex (CIC) and cryoglobulin in dengue-infected patients for identification of novel dengue severity biomarker(s). Totally, 100 clinically suspected dengue cases were tested by NS1 ELISA and MAC ELISA for dengue virus aetiology. For control, 49 healthy volunteers were included. Blood profiling (complete hemogram and liver function test) of patient population were done using automated cell counter and standard auto analyzer based biochemical analysis. Serum CIC was quantified by PEG precipitation. Serum cryoglobulins were estimated by Folin assay. Levels of serum IL-8 were assessed by standard sandwich ELISA kits. Patient CIC were further characterized by SDS Gel electrophoresis. Forty per cent of the cases tested positive, of which 11 patients had severe clinical manifestation. The mean +/-SEM of cryoglobulin concentration for DHF, DF, and HC were 1.30 +/- 0.31, 0.59 +/- 0.08 and 0.143 +/- 0.009 MUg/MUl, respectively. Thus, DHF and DF patients have shown 9- and 2.2-fold increase in cryoglobulin levels; and 18- and 5-fold increased CIC, respectively compared to HC patients. The mean +/-SEM of CIC-PEG index for DHF, DF and HC were 491 +/- 41.22, 146 +/- 14.19 and 27.98 +/- 2.56, respectively. Raised levels of IL8 titers were also found in all 11 DHF patients. Peak levels of CIC, cryoglobulin and IL8 titers were associated with thrombocytopenia. SDS PAGE analysis of CIC from DHF revealed the presence of at least six protein bands that were not observed in samples from DF and HC. Prediction efficacy of IL8, CIC and cryoglobulin for DHF was determined using the receiver operator characteristic curve (ROC). The area under the curve was 1.00 for IL8, 0.99 for CIC and 0.74 for cryoglobulins. Overall, the results suggest that CIC, IL-8 and cryoglobulins may serve as important laboratory parameters to monitor dengue infection progression. PMID- 26669015 TI - Molecular characterization and In silico analysis of Sorghum Panallergens: Profilin and Polcalin. AB - In India, 20-30% of the human population suffer from allergic rhinitis and 15% of them develop asthma. Plant pollens are one of the causative aeroallergens and are mixture of a number of molecules including major and minor allergens (Panallergens). Profilin and polcalcin are the known pollen specific panallergens. Allergenicity of the Sorghum plant in Andhra Pradesh was found to be 54.9%. But the allergens responsible have not been characterized well. This study highlights identification and molecular characterization of Sorghum bicolor profilin (Sorb PF) and S. bicolor polcalcin (Sorb PC) allergen genes based on homology. The coding sequences of the two genes were PCR amplified from the cDNA constructed from Sorghum pollen total RNA. The gene sequences were deposited in NCBI, KC427126 and KC427125. Recombinantly expressed histidine tag (His-tag) purified Sorghum polcalcin and profilin confirmed 9 and 14 kDa proteins, respectively. Based on multiple sequence alignment and phylogenetic analysis, Sorghum polcalcin and profilin were found to be closely related with Cynodon dactylon, Phleum pratense and Oryza sativa grass species. In silico Algpred based screening of SorbPF and SorbPC showed an allergenicity score of 1.149 and 0.879, respectively. The structure of two Ef-hand sequences (DTNGDGKISLSEL and DTDGDGFIDFNEF) of SorbPC showed an exact match with Phlp7. It is concluded that Sorghum recombinant profilin and polcalcin proteins can be of potential use in developing diagnostic kits for allergenicity to Sorghum pollen grains. PMID- 26669016 TI - Brugia malayi abundant larval transcript 2 protein treatment attenuates experimentally-induced colitis in mice. AB - Helminths are known to modulate host's immunity by suppressing host protective pro-inflammatory responses. Such immunomodulatory effects have been experimentally shown to have therapeutic implications in immune mediated disorders. In the present study, we have explored a filarial protein i.e. Brugia malayi recombinant abundant larval transcript 2 (rBmALT2) for its therapeutic effect in dextran sodium sulfate (DSS) induced colitis in mouse model. The immunomodulatory activity of rBmALT-2 was initially confirmed by demonstrating that it suppressed the lipopolysaccharide (LPS) induced nitric oxide synthesis and down-regulated the expression of pro-inflammatory cytokines in vitro by peritoneal exudate cells of mice. Treatment with rBmALT2 reduced severity of colitis associated with significant reduction in weight loss, disease activity, colon damage, mucosal edema and histopathological score including myeloperoxidase activity in colon tissues. rBmALT2 was comparatively more effective in attenuation of colitis when used in the preventive mode than when used for curative purpose. The therapeutic effect of rBmALT2 was found to be associated with downregulation of IFN-gamma, IL-6, IL-17 and upregulation of IL-10 cytokines. These results provide strong experimental evidence that BmALT2 could be a potential alternative therapeutic agent in colitis. PMID- 26669017 TI - Antiproteolytic and leishmanicidal activity of Coccinia grandis (L.) Voigt leaf extract against Leishmania donovani promastigotes. AB - In visceral leishmaniasis (VL), development of alternative safe therapeutic strategy is gaining paramount wherein natural components of plant origin have prominence. We explored Coccinia grandis (L.) Voigt, a medicinal plant known in traditional folk medicine, for its antileishmanial efficacy. SDS-PAGE analysis of the C. grandis leaf extract (Cg-Ex) showed few protein bands about 14-66 kDa among which three (64.8, 55.8 and 15.3 kDa) were identified as serine protease inhibitors by reverse zymography. Since the virulence of Leishmania is also attributed by serine proteases, objective of the present study was to evaluate in vitro antileishmanial activity of Cg-Ex, targeting Leishmania donovani serine protease(s). Inhibition study of Cg-Ex in gelatin-zymogram and spectrophotometric assay revealed its strong inhibitory activity against bovine trypsin rather than chymotrypsin, and also showed significant inhibition of L. donovani serine protease(s). Further, studies with Cg-Ex were extended to estimate its antileishmanial efficacy with half maximal inhibitory concentration (IC50) at 308.0 +/- 2.42 MUg/ml along with significant morphological alterations. The results have demonstrated the potential of the serine protease inhibitor rich fraction of the C. grandis leaf extract against visceral leishmaniasis. PMID- 26669018 TI - Bioactivity guided fractionation of Moringa oleifera Lam. flower targeting Leishmania donovani. AB - Leishmaniases is a group of diseases caused by the protozoan parasite belonging to the genus Leishmania. At least 20 species of Leishmania are known to infect humans transmitted by female sandflies, Phlebotomus spp. Leishmania donovani causes visceral leishmaniasis, considered most lethal among the common three forms of leishmaniasis. Lack of appropriate vaccines, emergence of drug resistance and side effects of currently used drugs stress the need for better alternative drugs, particularly from natural sources. Here, we conducted in vitro and in vivo experiments to study the efficacy of different parts of Moringa oleifera Lam. against Leishmania donovani promastigotes. The flower extract of M. oliefera (MoF) was found to be the most potent antileishmanial agent when compared to other parts of the plant like leaf, root, bark and stem. It imparted significant reduction in parasite number in infected macrophages. The bioactivity guided fractionation of MoF showed ethyl acetate fraction (MoE) as the most active and gave significant parasite reduction in the infected macrophages. Further, growth kinetics studies revealed loss of L. donovani promastigotes viability in the presence of MoE in both time and dose dependent manner. In vivo experiment in Balb/c mouse model of leishmaniasis supported the in vitro findings with a remarkable reduction of the parasite burden in both liver and spleen. PMID- 26669019 TI - Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte. AB - Ionizing radiation (IR) causes oxidative stress through overwhelming generation of reactive oxygen species (ROS) in the living cells leading the oxidative damage further to biomolecules. Grapevine (Vitis vinifera L.) posses several bioactive phytochemicals and is the richest source of antioxidants. In this study, we investigated V. vinifera for its phytochemical content, enzymes profile and, ROS- and oxidant-scavenging activities. We have also studied the fruit extract of four different grapevine viz., Thompson seedless, Flame seedless, Kishmish chorni and Red globe for their radioprotective actions in human lymphocytes. The activities of ascorbic acid oxidase and catalase significantly (P < 0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. Pretreatment with grape extracts attenuated the oxidative stress induced by 4 Gy gamma-radiation in human lymphocytes in vitro. Further, gamma-radiation-induced increase in caspase 3/7 activity was significantly attenuated by grape extracts. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars. PMID- 26669020 TI - Targeting folate metabolism for therapeutic option: A bioinformatics approach. AB - Lymphatic filariasis, commonly called elephantiasis, poses a burden of estimated level of 5.09 million disability adjusted life year. Limitations of its sole drug, diethylcarbamazine (DEC) drive exploration of effective filarial target. A few plant extracts having polyphenolic ingredients and some synthetic compounds possess potential dihydrofolate reductase (DHFR) inhibitory effect. Here, we postulated a plausible link between folates and polyphenolics based on their common precursor in shikimate metabolism. Considering its implication in structural resemblance based antagonism, we have attempted to validate parasitic DHFR protein as a target. The bioinformatics approach, in the absence of crystal structure of the proposed target, used to authenticate and for virtual docking with suitable tested compounds, showed remarkably lower thermodynamic parameters as opposed to the positive control. A comparative docking analysis between human and Brugia malayi DHFR also showed effective binding parameters with lower inhibition constants of these ligands with parasitic target, but not with human counterpart highlighting safety and efficacy. This study suggests that DHFR could be a valid drug target for lymphatic filariasis, and further reveal that bioinformatics may be an effective tool in reverse pharmacological approach for drug design. PMID- 26669021 TI - Life Is About Connections. PMID- 26669022 TI - Pennsylvania Coalition for Oral Health. MAKES STRIDES in Improving Oral Health Care for All. PMID- 26669023 TI - EPA Amalgam Separator Update. PMID- 26669024 TI - CLINICOPATHOLOGIC REVIEW: Periapical Radiolucencies & Routine Diagnostic Considerations. Normal anatomy. PMID- 26669025 TI - [Fedor Ivanovich Komarov (on the occasion of his 95th birthday anniversary)]. PMID- 26669027 TI - [ANTIOXIDANT THERAPY OF BRONCHIAL ASTHMA]. AB - This paper summarizes results of the investigations into the influence of antioxidants on the clinical picture of bronchial asthma. This disease is known to be accompanied by hyperactivation of lipid peroxidation. The use of antioxidants permits to correct free-radical oxidation (peroxidation) and enhances effectiveness of control over clinical symptoms. Moreover they more effectively improve external [Russian word: see text] than conventional therapy. PMID- 26669026 TI - [POSSIBILITIES FOR PHARMACOTHERAPY OF GASTROENTEROLOGICAL DISEASES DURING PREGNANCY]. AB - Modern views of the strategy for the treatment of the main gastroenterological diseases during pregnancy are considered. Peculiarities of the clinical course of digestive tract pathologies are discussed with reference to the influence of exacerbation of their chronic forms on fetus development. The most common gastroenterological pathologies include gastroesophageal reflux disease, gastric and duodenal disorders, acute and chronic pancreatitis, acalculous and calculous cholecystitis, hepatitis of autoimmune and other etiology, liver cirrhosis, intestinal inflammation. Possibilities of pharmacotherapy and its specific features in pregnant women are discussed including cases of exacerbation of chronic conditions. PMID- 26669028 TI - [EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS]. AB - The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%. PMID- 26669029 TI - [SCLEROSIS: LOCAL AND GENERAL PATTERNS OF DEVELOPMENT]. AB - Sclerosis is a final substrate and outcome of structural lesions of different organs and tissues in various pathological conditions, such as hypertensive disease, coronaty heart disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, rheumatoid arthritis, systemic scleroderma, etc. Not infrequently it as a determinant of severity and unfavourable outcome of the disease. Elucidation of general patterns of the development of sclerosis requires an integrated approach to the systemic analysis of clinical, genetic, biochemical, and morphological characteristics whereas a local analysis reveals peculiarities of formation of sclerosis in individual patients. Such combination permits to use methods of predictive-preventive personified medicine for planning the treatment of sclerosis. PMID- 26669030 TI - [THE COGNITIVE STATUS OF PATIENTS WITH TYPE 2 DIABETES MELLITUS AFTER CORONARY BYPASS SURGERY]. AB - The aim of the study was to evaluate the neuropsychological status of patients with type 2 diabetes mellitus (DM2) before and I year after coronary bypass surgery performed under conditions of artificial circulation. It included 114 patients (54 with and 60 without DM2). Prior to surgery, the patients with DM2 had positive characteristics of neurodynamics and attention. They deteriorated 1 year after coronary bypass surgery, but improved in the patients without DM2. PMID- 26669031 TI - [DIFFICULTIES OF DIFFERENTIAL DIAGNOSTICS OF SEVERE COMMUNITY-ACQUIRED PNEUMONIA]. AB - Severe community-acquired pneumonia implies the necessity of its early differential diagnostics from a wide range of nosological forms requiring not only therapeutic but also surgical treatment. The authors consider the causes of hypodiagnostics of community-acquired pneumonia and illustrate difficulties of differential diagnosis of this condition by concrete examples. PMID- 26669032 TI - [HOW APPROACHES TO PHARMACOTHERAPY OF ULCER DISEASE CHANGED FOR THE LAST 30 YEARS]. AB - Some 30-40 years ago, ulcer disease was treated with the use of a large amount of medications having different mechanisms of action. This approach is now substituted by a well-defined algorithm including courses of antisecretory therapy and eradication of Helicobacter pylori. Much attention is given to the optimization of the schemes of eradication therapy and prevention of erosive and ulcerative lesions of the stomach and duodenum associated with pharmacotherapy. PMID- 26669033 TI - [SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME]. AB - Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients. PMID- 26669034 TI - [ACUTE RESPIRATORY DISTRESS SYNDROME CAUSED BY BETA-LACTAM ANTIBIOTICS]. AB - We report a case of iatrogenic lesion of the lungs in a 61 year old patient following simultaneous subtotal resection and plastic surgery of esophagus using a gastric stem with the removed cardial portion along with subtotal mediastinal lympho-dissection for the treatment of 2 x 1 cm T2NoMO tumour in the middle third of esophagus. The patient's medical history contained no evidence of previous pulmonary pathology, preoperative chest X-ray study revealed neither focal nor infiltrative changes in the lungs. On day 5 after extensive surgical intervention with the use of a parenteral beta-lactam antibiotic, the patient developed acute respiratory distress the symptoms of which increased wavelike during the next 4.5 weeks in association with subfebrility, leukocytosis, enhanced ESR and large shaded areas in the lungs. These conditions were regarded as signs of pneumonia that required the application of increasingly more powerful beta-lactam antibiotics. All these symptoms became less apparent and completely disappeared within 2 days and 1 week respectively after withdrawal of the antibiotics and prescription of parenteral prednisolone. It confirmed the iatrogenic origin of lung lesions regarded by the authors as recurring acute respiratory distress syndrome caused by beta-lactam antibiotics. PMID- 26669035 TI - [CALCIFYING NANOPARTICLES IN PATHOMORPHOGENESIS OF STRUCTURAL LESIONS OF HEART VALVES]. AB - Over the last 10 years, calcifying nanoparticles (CNP) have attracted attention as structures detected. together with many other nanostructures in biopsies from patients operated for the correction of aortic valve malformations. The results of the present work performed with the use of high-resolution transmission and scanning electron microscopes agree on the whole with the data of other authors. Some new findings include CNP adhesion to collagen fibers and specifically shaped, shallow invaginations or craters at their surface. The possible pathophysiological mechanisms that promote involvement of CNP in the development of the disease are considered. PMID- 26669037 TI - [D.D. Pletnev--a great physician and scientist]. PMID- 26669036 TI - [ARTERIAL HYPERTENSION: A MODERN VIEW OF THE PROBLEM]. AB - This article deals with debatable problems of etiology, pathogenesis, and classification of hypertensive disease including essential kypertension, hypertonic crisis and methods of treatment of these conditions. PMID- 26669038 TI - [M.S. Vovsi--chief therapists of the Red Army]. PMID- 26669039 TI - [V.Kh. Vasilenko in the eyes of a pupil]. PMID- 26669040 TI - Mentoring for Collaborations and Team Science. PMID- 26669041 TI - Physiology--The Source of Nail-Biting Excitement in Kuala Lumpur! PMID- 26669042 TI - Great expectations. PMID- 26669043 TI - Courage: triumph over fear. PMID- 26669044 TI - NMC takes momentous decision to launch revalidation. PMID- 26669045 TI - Survey finds maternity services struggling to cope. PMID- 26669046 TI - No evidence for 'safe' drinking in pregnancy. PMID- 26669047 TI - Pelvic girdle pain: updating current practice. AB - Traditionally, pelvic girdle pain (PGP) was viewed as a hormonal problem, untreatable during pregnancy and exacerbated by the weight of the baby. Customary advice was for rest, support belts and to await recovery following the baby's birth. However, the outcome of this management resulted in many women experiencing short or long-term physical disability, as well as the psychological impact of pain and immobility. Recent research links an asymmetry of the pelvic joints to the incidence and severity of PGP and shows the cause is biomechanical and not due to pregnancy hormones. Evidence supports manual therapy as the effective way to resolve PGP quickly during pregnancy through a realignment and restoration of symmetry of movement in the pelvic joints, thereby avoiding the adverse long-term consequences of the condition. PMID- 26669048 TI - From pregnancy to palliative care: advancing professional midwifery practice? AB - Historically midwives may have not considered palliative care as a part of their professional role. Enhanced technologies and antenatal screening have broadened the boundaries of care. However do midwives truly embrace the philosophy of palliative care into their practice? This paper presents the discussion round a case study that demonstrates the evolving area of advanced practice: perinatal palliative care. What we highlight is that midwives in fact have an important collaborative role to play in ensuring that palliative care for the baby and family starts as soon as a life-limiting condition is recognised, thus ensuring best care and support are provided for those parents and families for whom pregnancy sadly leads to palliative care. Five key lessons for practice are outlined. PMID- 26669049 TI - Unexpected breech: what can midwives do? AB - Approximately 1:100-150 women at term experience diagnosis of breech presentation for the first time in labour (Walker 2013). Such an unanticipated discovery is stressful for both women and the healthcare professionals who care for them. Undiagnosed breech experiences can leave midwives and women elated, distressed or disempowered. This article suggests practical ways midwifery change leaders can improve care for undiagnosed breeches within organisations: plan or scan antenatally, and identify a multi-disciplinary breech leadership team for support, reflection and collaborative professional development. PMID- 26669050 TI - Sweet memories of a bitter experience: a parent's view. AB - Having an extremely preterm baby is the most difficult time for parents. It becomes even more stressful if the preterm birth was unexpected. This article reflects the personal experiences of a paediatric trainee on having his first baby as unexpectedly very preterm. He shares his feelings of joy and uncertainty, which a parent can experience during these difficult times. A paediatric trainee, on the one hand, and the new parent of a sick baby on the other, this was an eye opener and gave him real insight into parents' feelings in similar circumstances during his own clinical practice. This has motivated him to write this article to empathise with parents and share his learning points with other health professionals. PMID- 26669051 TI - Unexpected consequences of midwifery in the NHS. AB - This article presents information from the Caring for the carers conference held at George Eliot Hospital in July 2015. For many midwives, feelings of stress are an unexpected consequence of rising birth rates, low staffing levels and negative organisational cultures, so our aim was that delegates would take away skills for 'surviving' in maternity services. The conference was the catalyst to a project at George Eliot NHS Trust to improve the wellbeing of staff so that they can develop a positive outlook towards the care which they offer. As part of the project, a toolkit for survival was produced which helps to prompt maternity workers to remember their own wellbeing. This project is continuing to grow and the results will be available next year. PMID- 26669052 TI - On running for supervisor. AB - As reflection has become a firmly integrated element of good practice, and fundamental to the concept of learning from experience, individuals frequently utilise their own creativity and unique thought processes to make sense of their personal challenges. This paper uses the analogy of running a race to explore the personal challenge of undertaking preparation and study to become a supervisor of midwives (SoM), and to consider the unknown challenges ahead. This analogy gave rise to a unique and personal reflective cycle that incorporates traditional and familiar reflective models alongside acknowledgement of the physical and emotional advantages of physical exertion. PMID- 26669053 TI - Keeping the shining roads open: intuition in midwifery practice. AB - Within the midwifery profession, intuition has been discussed for many years and examined as both an obstructive and productive element of clinical practice. Intuitive ability is perceived by some to diminish the basis from which good clinical decisions are made, based upon the argument that intuitive knowledge is not evidence based. However, research has shown that midwives frequently rely on their 'gut' instincts or intuitive insights as the foundation of a judgement or action within the clinical practice setting. PMID- 26669054 TI - 2. Newly qualified midwives. AB - Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this second article of the series, Kerry Taylor, Stephanie Heys and Jessemy Evans look first hand at the positive and negative aspects of a preceptorship programme from the view of newly qualified midwives, and offer top tips. to help other newly qualified midwives embarking on their exciting new careers. PMID- 26669055 TI - Wavering enthusiasm. AB - This reflection focuses on an experience I had whilst on my community placement involving my first birth, a home birth. I attended as a student midwife. In order to maintain confidentiality I have used pseudonyms throughout. I have mulled over my feelings about the first birth I witnessed, and midwifery as my future career and, most importantly, the role of the midwife at a home birth. PMID- 26669056 TI - Pondering placentophagy. Part 2. AB - A recent systematic review, which looked at whether there are any benefits to placentophagy--the consumption of one's placenta after birth--has concluded that there is no evidence of benefit or risk and that these require further investigation. In the first part of this article, I reflected on this practice and noted some of the difficulties in evaluating such a practice. In this second article, I ask whether the claim that this is an age-old or natural practice is useful, consider why this might be important for women and explore some of the issues that we might want to consider in relation to this and other practices for which we have no evidence. PMID- 26669057 TI - Soranus (Part 1). PMID- 26669058 TI - EMS TODAY 2016. Making good on important promises. PMID- 26669060 TI - AUTHOR STEVE WIRTH, ESQ., EMT-P, RESPONDS. PMID- 26669059 TI - QUESTIONING COPS. PMID- 26669061 TI - PASS IT ON. Mentoring employees benefits everyone. PMID- 26669062 TI - CRASH & COMPRESSION. Dump truck pins patient in his car. PMID- 26669063 TI - TRIAGING GERIATRICS. 110 is the new 90 for systolic blood pressure in elderly patients. PMID- 26669064 TI - CRITICAL STRESS. Survey reveals alarming rates of EMS provider stress & thoughts of suicide. PMID- 26669065 TI - HEAD & SHOULDERS. Prehospital treatment of athletes wearing a helmet & shoulder pads. PMID- 26669066 TI - UNDER POLICE CONTROL. Understanding & treating trauma caused by law enforcement use of force. PMID- 26669067 TI - REPORTED SEXUAL ASSAUT. Emotional first aid & the facilitation of justice Reported sexual assault. PMID- 26669068 TI - SERIAL INEBRIATES. Albuquerque Fire & Police Departments team up on community EMS project Serial inebriates. PMID- 26669070 TI - STAYING INFORMED. Help clinicians take control of the self-directed learning process. PMID- 26669069 TI - The BVM Effect. An overview of studies assessing airway management in out-of hospital cardiac arrest. AB - Numerous studies addressing airway management in OHCA have shown a strong association between improved survival with treatment using BVM alone rather than with advanced airways. This BVM effect appears to persist despite variations in geographical region, patient population, and CPR quality. The underlying cause of this phenomenon remains to be determined. Of note, the survival benefit with BVM alone vs. advanced airways doesn't appear in the pediatric population in the papers reviewed by the authors. The authors recommend that a prospective randomized study be conducted in order to explore this finding and to attempt to determine its causation. PMID- 26669071 TI - MAGNETS. What kind of calls do you attract? PMID- 26669072 TI - [Hyperphosphatemia in Chronic Kidney Disease (CKD)]. AB - Phosphorus plays important roles in a variety of biological processes such as energy metabolism, cell signaling, nuclenic acid synthesis and membrane function. A major role of the kidney is to maintain phosphorus homeostasis. It is not surprising that when renal function begins to decline in CKD patients, the homeostasis is disrupted and serum concentration of phosphorus begins to increase. Hyperphosphatemia leads to a series of complications including secondary hyperparathyroidism, renal osteodystrophy, cardiovascular diseases and progression of CKD, which contributing to the excess mortality of CKD. In recent years, as an independent risk factor of health damage, hyperphosphatemia has attracted more and more concerns. The progression of researches about hyperphosphatemia has promoted the clinical therapies of CKD. PMID- 26669073 TI - [Research Progress of Klotho]. AB - Klotho, a newly identified anti-aging gene, can be regulated by many factors, such as calcitonin gene-related peptide, fibroblast growth factor 2 could up regulate Klotho expression; whereas renin-angiotensin system, urinary toxins, inflammation and oxidative stress could reduce expression of Klotho. There are two forms of Klotho protein: membrane-bound Klotho and secreted Klotho. Existing studies showed that Klotho was involved in the development of many diseases, including vascular calcification, atherosclerosis, hypertension, kidney damage, hyperparathyroidism, diabetes and tumors. In this paper, the regulation of Klotho expression and its role in diseases are reviewed briefly. PMID- 26669074 TI - [The Relationship Between GSK-3 and Mental Disorders]. AB - Glycogen synthase kinase 3 ( GSK-3) is a constitutive serine/threonine kinase, which plays a important role in many essential physiological activities, and regulates cellular processes including metabolism, development and apoptosis through a number of signaling pathways such as Wnt/beta-catenin. Numbers of studies claimed that abnormal regulation of GSK-3 may activate several differential cells, pathways and loops, and bring out the mental disorder, including bipolar disorder, depression, anxiety, schizophrenia and so on. Inhibiting GSK-3 plays an important role in therapy for mental diseases. This review summed up the mechanism of how GSK-3 does work in mental diseases at home and abroad recent years, and hoping to provide basis for clinical treatment. PMID- 26669075 TI - [Present Situation and Prospect of Urinary Biomarkers For Bladder Cancer]. AB - Bladder cancer is one of the most common cancers in the world. Early detection of bladder cancer is critical to improve the prognosis of the patient. The conventional method for the detection and monitoring of bladder cancer at present is cystoscopy with urinary cytology. Limitations of cystoscopy and urinary cytology have shown the need for better diagnostic method for bladder cancer. Ideally, such assays would be applicable to noninvasively obtained, and be designed not only for diagnosis, but also for monitoring disease recurrence and providing basis for therapy. Consequently, the development of a noninvasive urine based assay would bring the gospel to both patients and healthcare systems. This article reviews some of the more prominent urine-based biomarkers and related new technologies reported in the literature in recent years. PMID- 26669076 TI - [Tetrahydrobiopterin Synthesis and Biological Function]. AB - Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases and all three nitric oxide synthase (NOS) isoforms. It has protective effects as an antioxidant and scavenger of reactive nitrogen and oxygen species. It also serves as a cofactor in both normal physiologic and pathological states. In conditions of BH4 deficiency, endothelial nitric oxide synthase (eNOS) becomes 'uncoupled', which leads to endothelial dysfunction in diabetes, pulmonary hypertension and pathologic cardiac remodeling. In this review, we will discuss the pathophysiological role of BH4 in those diseases mentioned above. PMID- 26669078 TI - [Allostasis--stability through change]. PMID- 26669077 TI - [Research Progress in Mixed Lineage Kinase Domain-Like]. AB - Necroptosis is a novel programmed cell death mechanism which is caspase independent. It is mediated by specific signaling via a death receptor ligation. Necroptosis usuaUy arises when the apoptotic Pathway is inhibited, and is characterized by a necrotic morphology. Recently many reports have revealed that necroptosis is precisely regulated by a cellular signaling pathway, like apoptosis. Receptor interaction protein kinase 1 and receptor interaction protein kinase 3 kinases are the key regulators of this alternative cell death mechanism. MLKL plays an important role in TNF-induced programmed necrosis pathway. In this paper physiological function and molecular mechanism were reviewed. PMID- 26669079 TI - [Posttranslational modifications of SIRT1 and its function]. PMID- 26669080 TI - [Biological function of miR-122 and its relationship with liver diseases]. PMID- 26669081 TI - [The role of the retinoid-related orphan receptor alpha in the regulation of lipid metabolism]. PMID- 26669082 TI - [Function and expression of inwardly rectifying potassium channel Kir2.1]. PMID- 26669083 TI - [The expanding of canonical hypoxia-inducible factor pathway and the regulation of stem cell]. PMID- 26669084 TI - [Chronic insomnia disorder--the clinical and mechanism study of paradoxcial insomnia]. PMID- 26669085 TI - [A novel myokine: vascular endothelial growth factor B]. PMID- 26669086 TI - [Correlation of the FTO gene single nucleotide polymorphism and disease]. PMID- 26669087 TI - [Autophagy during cardiac stress: is the autophagy beneficial for detrimental]. PMID- 26669088 TI - [Autophagy and pulmonary fibrosis]. PMID- 26669089 TI - [The functions of dopamine transport and its relation with neuropsychiatric diseases]. PMID- 26669091 TI - Preface. PMID- 26669092 TI - Antimycobacterial Natural Products from Endophytes of the Medicinal Plant Aralia nudicaulis. AB - Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (isolate HL6-097-027B) isolated from the rhizomes of the Canadian medicinal plant Aralia nudicaulis were found to contain palitantin (1) and botrallin (2), craterellin C (3), mycosporulone (4), spiromassaritone (5), and massarigenin D (6) respectively. Bioassays against Mycobacterium tuberculosis H37Ra revealed that 1 - 4 possess moderate antimycobacterial activity. PMID- 26669093 TI - Microsporols A-C from the Plant Endophytic Fungus Pestalotiopsis microspore. AB - Three new ambuic acid derivatives, microsporols A-C (1-3) and the known compound ambuic acid (4), were isolated from the solid-substrate fermentation cultures of the plant endophytic fungus Pestalotiopsis microspora. Their structures were elucidated primarily by NMR experiments. The absolute configurations of the 6,7 diol moiety in 1 and 2 were assigned using the Snatzke's method, whereas that of 3 was deduced by circular dichroism (CD) exciton chirality method. Compounds 1, 3, and 4 showed moderate 5-lipoxygenase (5-LOX) inhibitory effects. PMID- 26669094 TI - Isolation of Phomopsolide A and 6(E)-Phomopsolide A as Antimycobacterial Natural Products from an Unidentified Endophyte of the Canadian Medicinal Plant Heracleum maximum. AB - An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhibited a unique metabolomic profile and significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation of the extract led to the isolation of phomopsolide A (1) and 6(E)-phomopsolide A (2). This is the first report of antimycobacterial activity for 1 and 2. PMID- 26669095 TI - Pyrrolocin A, a 3-Decalinoyltetramic Acid with Selective Biological Activity, Isolated from Amazonian Cultures of the Novel Endophyte Diaporthales sp. E6927E. AB - Natural products remain an important source of new therapeutics for emerging drug resistant pathogens like Candida albicans, which particularly affects immunocompromised patients. A bioactive 3-decalinoyltetramic acid, pyrrolocin A, was isolated from extracts of a novel Amazonian fungal endophyte, E6927E, of the Diaporthales family. The structure of the natural product was solved using NMR and CD spectroscopy and it is structurally related to the fungal setins, equisetin and phomasetin, which are well-characterized tetramic acid antibiotics specific for Gram-positive organisms. We show that the compound inhibits growth of Staphylococcus aureus and Enterococcus faecalis. It shows selective and potent bioactivity against fungal strains, with an MIC of 4 MUg/mL for C. albicans, 100 MUg/mL for Aspergillus sp. and greater than 100 MUg/mL for Saccharomyces cerevisiae. Further, the compound is less toxic to mammalian cells (IC50 = 150 MUg/mL), with an inhibitory concentration greater than forty times that for C. albicans. Pyrrolocin A retained potent activity against eight out of seventeen strains of clinical Candida sp. isolates tested. PMID- 26669096 TI - Cytotoxic Cytochalasins and Other Metabolites from Xylariaceae sp. FL0390, a Fungal Endophyte of Spanish Moss. AB - Two new metabolites, 6-oxo-12-norcytochalasin D (1) and 4,5-di-isobutyl-2(1H) pyrimidinone (2), together with seven known metabolites, cytochalasins D (3), Q (4), and N (5), 12-hydroxyzygosporin G (6), heptelidic acid chlorohydrin (7), (+) heptelidic acid (8), and trichoderonic acid A (9), were isolated from Xylariaceae sp. FL0390, a fungal endophyte inhabiting Spanish moss, Tillandsia usneoides. Metabolite 1 is the first example of a 12-norcytochalasin. All metabolites, except 2 and 9, showed cytotoxic activity in a panel of five human tumor cell lines with IC50S of 0.2-5.0 MUM. PMID- 26669097 TI - Endophytic Fungus Nigrospora oryzae from a Medicinal plant Coccinia grandis, a High Yielding New Source of Phenazine-1-carboxamide. AB - Nigrospora oryzae was isolated as an endophytic fungus from the leaves of Coccinia grandis, a popular medicinal plant used to control diabetes. Fermentation of the fungus in potato dextrose broth and chromatographic purification of the ethyl acetate extracts of the broth and mycelium yielded two phenazine secondary metabolites, which were identified as phenazine-1-carboxylic acid (1) and phenazine-1-carboxamide (2) by comparing their spectral data with those reported in the literature. Compound 2, isolated in high yield (1 g/4 L medium), showed strong antifungal activity against the plant pathogen Cladosporium cladosporioides. This is the first report of the isolation of N. oryzae as an endophytic fungus of C. grandis. These phenazines have never been isolated from any fungal source. Antifungal activity of 2 against C. cladosporioides is reported for the first time. PMID- 26669098 TI - Polyketides from an Endophytic Aspergillus fumigatus Isolate Inhibit the Growth of Mycobacterium tuberculosis and MRSA. AB - The crude extract of Aspergillusfumigatus isolate AF3-093A, an endophyte of the brown alga Fucus vesiculosus, showed significant antimicrobial activity in initial bioactivity screens. Bioassay-guided fractionation of the extract led to the isolation of flavipin, chaetoglobosin A and chaetoglobosin B, all of which inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium tuberculosis H37Ra. The antimycobacterial activity of these compounds has not been previously reported. PMID- 26669099 TI - A 3-Vinyl Cephem Derivative, a Useful Intermediate in the Synthesis of Cepham Antibiotics, from Aspergillus awamori Associated with Banana Fruit. AB - Aspergillus awamori was isolated from a diseased banana fruit, Musa acuminata cv. Ambul. The fungus was fermented in potato dextrose broth and on potato dextrose agar media and the fungal media were extracted with EtOAc. Chromatographic separation of the EtOAc extracts furnished 4-methoxybenzyl 7-phenylacetamido-3 vinyl-3-cephem-4-carboxylate (1), along with three naphtho-gamma-pyrones, flavasperone (2), foncesinone A (3) and aurasperone A (4), and three alkaloids, aspernigrin A (5), pestalamide C (6) and nigragillin (7). Compound 1, a known key intermediate in the chemical synthesis of cepham antibiotics, was isolated from a natural source for the first time. Compound 1 is the first 3-vinyl cephem derivative of microbial origin. PMID- 26669100 TI - Two New Cyclic Depsipeptides from the Endophytic Fungus Fusarium sp. AB - Two new cyclic depsipeptides, W493 C (1) and D (2), along with two known derivatives W493 A (3) and B (4) were obtained from the endophytic fungus Fusarium sp. isolated from the Mangrove plant Ceriops tagal. The structures of the new compounds were determined on the basis of one- and two dimensional NMR and high-resolution mass spectroscopic data. The absolute configurations of the amino acid residues of 1 and 2 were confirmed by application of Marfey's method. W493 A (3) and B (4) exhibited moderate activity against the fungus Cladosporium cladosporiodes and weak antitumor activity against the human ovarian cancer cell line A2780. PMID- 26669102 TI - Anti-diabetic Effect of Friedelan Triterpenoids in Streptozotocin Induced Diabetic Rat. AB - We herein report the anti-diabetic effect of the natural friedelan tritepenoid, 4 oxa-3, 4-secofriedelan (cerin), isolated from cork tissue of Quercus suber L. and its oxygenated derivative, 4-oxa-3, 4-secofriedelan-3-oic acid (cerin(ox)) in streptozotocin (STZ)-induced diabetic rat. Male Sprague Dawley rats were randomized into four groups: non-diabetic control (Group I), STZ-induced diabetic rats (Group II), STZ-induced diabetic rats treated with cerin (Group III), and STZ-induced diabetic rats treated with cerin(ox), (Group IV). Administration of cerin (3 mg/kg) and cerin(ox), (3 mg/kg) orally to STZ-diabetic rats for three weeks improved the body weight, reduced serum glucose level and activities of alkaline phosphatase, acid phosphatase, glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase, and restored liver antioxidant status. PMID- 26669101 TI - Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers. AB - This is a review of bioactive secondary metabolites isolated from conifer associated endophytic fungi from 1990-2014. This includes compounds with antimicrobial, anti-inflammatory, anti-proliferative and cytotoxic activity towards human cancer cell lines, and activity against either plant pathogens or plant insect pests. Compounds that were originally reported without associated activity were included if other studies ascribed activity to these compounds. Compounds were not included if they were exclusively phytotoxic or if they were isolated from active extracts but were not determined to be the active component of that extract. PMID- 26669104 TI - (+)-Chenabinol (Revised NMR Data) and Two New Alkaloids from Berberis vulgaris and their Biological Activity. AB - A known alkaloid (+)-chenabinol (1) and two new secobisbenzylisoquinoline alkaloids were isolated by standard chromatographic methods from the root bark of Berberis vulgaris L. The structures of the new alkaloids, named berkristine (2) and verfilline (3), were established by spectroscopic (including 2D NMR), and HRMS (ESI) methods. The alkaloids were tested for their inhibition activity of human cholinesterases and prolyl oligopeptidase. Compound 1 inhibited human butyrylcholinesterase with an IC50 value of 44.8 +/- 5.4 MUM. PMID- 26669103 TI - Colochirosides B1, B2, B3 and C, Novel Sulfated Triterpene Glycosides from the Sea Cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). AB - Four new triterpene glycosides, colochirosides B1 (1), B2 (2), B3 (3) and C (4) have been isolated from the sea cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). Six known earlier glycosides from representatives of two families of the order Dendrochirotida have also been found in C. robustus. Structures of the glycosides have been elucidated by 2D NMR spectroscopy and mass spectrometry. All the glycosides belong to the holostane series and contain tetrasaccharide linear carbohydrate chains with one or two sulfate groups. Cytotoxic activities of glycosides 1-4 against the ascite form of mouse Ehrlich carcinoma cells and hemolytic activities against mouse erythrocytes have been studied. Hemolytic activity of the glycosides was higher than cytotoxic. Glycosides 3 and 4 demonstrated strong effects, whereas compounds 1 and 2 containing the hydroxy-group in the side chains showed moderate hemolytic activity and were not cytotoxic. PMID- 26669105 TI - The Influence of Cultivars and Phenological Phases on the Accumulation of Nevadensin and Salvigenin in Basil (Ocimum basilicum). AB - According to the earlier literature the optimum harvest time for basil is at the full flowering stage if accumulation of essential oil is taken into account. In this research we have investigated our gene-bank stored basil accessions to determine whether the harvest timing is variety specific or not considering their flavonoid accumulation pattern. In our work we have determined by HPLC the content of two main flavonoid compounds, salvigenin and nevadensin, of eight different gene bank accessions from 2013 of Ocimum basilicum L. Data were analysed with the nonparametric Kruskal-Wallis test. Multiple pairwise comparisons were made using the Conover-Iman procedure where the significance level was 5%. We have observed that the optimum harvest time is at the full flowering stage in the case of accessions 'Genovese' and 'Piros', but this was not verified for the others. The result of our experiment has shown that the maximum salvigenin and nevadensin content was detected both at the full- and early flowering period. Almost in all phenological phases the accession 'M. Grunes' accumulated the highest level of nevadensin, while accession 'Lengyel' produced the lowest results in all phenological phases. Generally it could be observed that compared with nevadensin more salvigenin is accumulated, and it is independent of the phenological phases. In the case of salvigenin, 'M. Grunes' accession produced the largest quantity and accession 'Dark Opal' showed the lowest values. Our analyses demonstrated that harvest at different phenological phases may result in different amounts of active agents according to the cultivar. PMID- 26669106 TI - Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa. AB - Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5 LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 MUM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species. PMID- 26669107 TI - Secondary Metabolites of Alchemilla persica Growing in Iran (East Azarbaijan). AB - Phytochemical investigations of Alchemilla persica Rothm. growing in Iran were performed taking into account both the volatile and polar constituents. The hydrodistilled essential oil was analysed by GC-MS that revealed the presence of alkanes (27.8%), diterpenoids (19.6%) and sesquiterpene hydrocarbons (17.1%) as the major constituents, while tannins and flavonol glycosides were identified as the most abundant constituents of the methanol extract by HPLC-MS. A. persica can be a valuable source of ellagitannins and polyphenols. PMID- 26669108 TI - A Novel Ellagic Acid Derivative from Desbordesia glaucescens. AB - One novel ellagic acid derivative, desglauside (1), was isolated from the leaves of Desbordesia glaucescens together with three known compounds [3',4'-di-O methylellagic acid (2), oleanolic acid (3) and beta-sitosterol-3-O-beta-D glucopyranoside (4)]. Their structures were elucidated on the basis of NMR spectroscopic and MS analysis, and by comparison with related published data. The crude extract, fractions and isolated compounds showed no activity against four yeast strains [Candida albicans (ATCC 9002), C. parapsilopsis (ATCC22019), C. tropicalis (ATCC750), Cryptococcus neoformans (IP95026) and one isolate of Candida guilliermondii]. PMID- 26669109 TI - Proliferative Constituents from the Leaves of Micromelum integerrimum. AB - Two new compounds, 5-O-methyl-4-desmethyl-myricanol (1) and 6-formyl-5-isopropyl 3-hydroxymethyl-7-methyl-1H-indene (2), were isolated from the leaves of Micromelum integerrimum. Their structures were determined by spectroscopic methods. Additionally, compound 1 could stimulate the growth of NIH3T3 cells and promote cell migration. Compound 1 might exert its effects through increasing the protein expression of connective tissue growth factor. PMID- 26669110 TI - Xylactam B, A New Isobenzofuranone from an Endophytic Xylaria sp. AB - A new nitrogen containing compound named xylactam B (2), along with a further eight known compounds, ceramide 2a, cerebroside B, cyclo(prolyl,valyl), marmesin, 5-methoxycarbonylmellein, 5-methylmellein, polypropylene glycol and p hydroxybenzoic acid, were isolated from an endophytic Xylaria sp. The structure elucidation of the new compound and the other isolates was carried out with the help of spectroscopic analyses and databases. PMID- 26669111 TI - Separation of Aeruginosin-865 from Cultivated Soil Cyanobacterium (Nostoc sp.) by Centrifugal Partition Chromatography combined with Gel Permeation Chromatography. AB - Aeruginosin-865 was isolated from cultivated soil cyanobacteria using a combination of centrifugal partition chromatography (CPC) and gel permeation chromatography. The solubility of Aer-865 in different solvents was evaluated using the conductor-like screening model for real solvents (COSMO-RS). The CPC separation was performed in descending mode with a biphasic solvent system composed of water-n-BuOH-acetic acid (5:4:1, v/v/v). The upper phase was used as a stationary phase, whereas the lower phase was employed as a mobile phase at a flow rate of 10 mL/min. The revolution speed and temperature of the separation column were 1700 rpm and 25 degrees C, respectively. Preparative CPC separation followed by gel permeation chromatography was performed on 50 mg of crude extract yielding Aer-865 (3.5 mg), with a purity over 95% as determined by HPLC. The chemical identity of the isolated compound was confirmed by comparing its spectroscopic data (UV, HRESI-MS, HRESI-MS/MS) with those of an authentic standard and data available in the literature. PMID- 26669112 TI - Effect of Maturation Degree on Composition of Fatty Acids and Tocopherols of Fruit Oil from Pistacia atlantica Growing Wild in Algeria. AB - Pistacia atlantica fruit oil has been used for a long time by local populations for culinary and medicinal purposes. In this study, the fatty acid composition and tocopherol content were determined in twelve samples of P. atlantica fruit oil at three stages of maturation (immature, intermediate maturity and mature) collected in three different sites from the region of Laghouat. The results indicated a significant difference between the oil of mature fruits (green and black) and the immature ones (light red), which were distinguished by richness in unsaturated fatty acids and tocopherols. The oil from fruits of intermediate maturity (dark red) seems to combine these properties with those of the mature group, including oil yields. Such data emphasize the value of this oil, which needs further investigation. PMID- 26669113 TI - Chemoenzymatic Total Synthesis of (R)-4-Dodecanolide and (R)-4-Octanolide. AB - A simple and efficient chemoenzymatic total synthesis of the naturally occurring insect pheromones, (4R)-dodecanolide and (4R)-octanolide is described. PMID- 26669114 TI - Inspired by Nature: The Use of Plant-derived Substrate/Enzyme Combinations to Generate Antimicrobial Activity in situ. AB - The last decade has witnessed a renewed interest in antimicrobial agents. Plants have received particular attention and frequently rely on the spontaneous enzymatic conversion of an inactive precursor to an active agent. Such two component substrate/enzyme defence systems can be reconstituted ex vivo. Here, the alliin/alliinase system from garlic seems to be rather effective against Saccharomyces cerevisiae, whilst the glucosinolate/myrosinase system from mustard appears to be more active against certain bacteria. Studies with myrosinase also confirm that enzyme and substrate can be added sequentially. Ultimately, such binary systems hold considerable promise and may be employed in a medical or agricultural context. PMID- 26669115 TI - Effect of Supplementation with Wheat Bran Aqueous Extracts Obtained by Ultrasound Assisted Technologies on the Sensory Properties and the Antioxidant Activity of Dry Pasta. AB - Phenolic compounds have antioxidant properties and activate endogenous detoxification defense systems able to scavenge the reactive species of oxygen. The external layers of wheat caryopsis, largely constituting by-products of the milling industry such as bran and various middlings, contain relevant amounts of phenolic compounds. The aim of the research has been to evaluate the effect of supplementation with wheat bran aqueous extracts, obtained by ultrasound-assisted technologies, on the sensory properties and antioxidant activity of dry pasta. The HPLC-DAD characterization of the extract evidenced the presence of ferulic and p-coumaric acids. The supplemented pasta showed significantly higher antioxidant activity and phenolic content than the control, coupled to good overall sensory judgment. In addition, two different pasta drying diagrams were adopted, and the comparison of the corresponding end-products allowed it to be pointed out that the processing technology has to be carefully set up to prevent possible detrimental effects on the antioxidant activity. The proposed utilization of bran might add value to a milling by-product that, otherwise, is mostly employed in animal feeding. PMID- 26669116 TI - Development of SCAR Markers Based on Improved RAPD Amplification Fragments and Molecular Cloning for Authentication of Herbal Medicines Angelica sinensis, Angelica acutiloba and Levisticum officinale. AB - Molecular cloning from DNA fragments of improved RAPD amplification of Angelica sinensis, Angelica acutiloba and Levisticum officinale, provided novel sequence characterized amplified region (SCAR) markers A13, A23, A1-34 and A1-0 whose sequences were deposited in the GenBank database with the accession numbers KP641315, KP641316, KP641317 and KP641318, respectively. By optional PCR amplification, the SCAR markers A13 and A23 are Levisticum officinale-specific, whereas the SCAR marker A1-34 is Angelica acutiloba-specific, and the SCAR marker A1-0 is Angelica sinensis-specific. These diagnostic SCAR markers may be useful for genetic authentications, for ecological conservation of all three medicinal plants and as a helpful tool for the genetic authentication of adulterant samples. PMID- 26669117 TI - Chemical Composition of Blumea lacera Essential Oil from Nepal. Biological Activities of the Essential Oil and (Z)-Lachnophyllum Ester. AB - The essential oil from the aerial parts of Blumea lacera collected from Biratnagar, Nepal, has been obtained by hydrodistillation and analyzed by gas chromatography - mass spectrometry. The major component from the oil, (Z) lachnophyllum ester, was isolated by preparative silica gel chromatography. B. lacera oil was dominated by (Z)-lachnophyllum ester (25.5%), (Z)-lachnophyllic acid (17.0%), germacrene D (11.0%), (E)-beta-farnesene (10.1%), bicyclogermacrene (5.2%), (E)-caryophyllene (4.8%), and (E)-nerolidol (4.2%). Also detected in the oil were (E)-lachnophyllic acid (3.3%) and (E)-lachnophyllum ester (1.7%). (Z) Lachnophyllum ester exhibited cytotoxic activity against MDA-MD-231, MCF-7, and 5637 human tumor cells, as well as antibacterial and antifungal activity. PMID- 26669118 TI - Essential Oil Composition and Antibacterial Activity of Hyptis colombiana from the Venezuelan Andes. AB - Hyptis colombiana is an aromatic shrub native to the Colombian and Venezuelan Andes. Aerial parts were collected in Merida State at about 3100 m above sea level in February 2005, and May and October 2006. The essential oil was found to contain germacrene D and beta-caryophyllene as main constituents (about 50%). The February 2005 and October 2006 oils were found to have antibacterial activity against Staphylococcus aureus, but not the May 2006 oil, probably due to the lack of some minor constituent. PMID- 26669119 TI - Repellent and Anti-quorum Sensing Activity of Six Aromatic Plants Occurring in Colombia. AB - Essential oils (EOs) are widely used as biopesticides and to control bacterial infections. This study describes the ability of six EOs isolated from plants cultivated in Colombia to perform as repellents against Ulomoides dermestoides and as quorum sensing (QS) inhibitors. EOs from Aloysia triphylla, Cymbopogon nardus, Lippia origanoides, Hyptis suaveolens, Swinglea glutinosa and Eucalyptus globulus were repellents classified as Class IV, IV, IV, III, II, and II, respectively, whereas the commercial repellent IR3535 only reached Class II after 2 h exposure. All EOs presented small, but significant inhibitory properties against the QS system in Escherichia coli (pJBA132) at 25 MUg/mL after 4 h exposure. These data suggest evaluated EOs from Colombia are sustainable, promising new sources of natural repellents and could be important as anti-quorum sensing molecules. PMID- 26669120 TI - Chemical Composition and Larvicidal Activity of Greek Myrtle Essential Oils against Culex pipiens biotype molestus. AB - Fresh leaves of Myrtus communis collected from different localities in Greece, were subjected to hydrodistillation and the oils obtained were analyzed by GC-FID and GC-MS. The analyses showed mainly quantitative differences, with the monoterpenes myrtenyl acetate, alpha-pinene, 1,8-cineole, and linalool, along with limonene, dominating the majority of the analyzed Myrtle oils. The evaluation of the larvicidal activity of the samples against Culex pipiens biotype molestus mosquito showed that all tested samples exhibited moderate to weak toxicity, with cultivated M. communis subsp. communis oil being the most active. PMID- 26669121 TI - Chemical Composition Variability of the Herb Essential Oil in the Ontogenesis of Artemisia campestris subsp. campestris. AB - The essential oil from the herb of Artemisia campestris L. subsp. campestris harvested at five ontogenesis phases was analyzed by GC, GC/MS and 1H NMR spectroscopy. More than 130 compounds were identified. Terpene hydrocarbons dominated in the oil. Germacrene D (20.3-30.1%), beta-pinene (3.7-15.4%) and gamma-humulene (6.6-9.8%) were the main constituents. The contents of germacrene D and gamma-humulene decreased from the phase before bud formation to the beginning of flowering, then increased until the post-flowering phase. The content of beta-pinene at the same periods firstly increased, and then was reduced. PMID- 26669122 TI - Sesquiterpenes from Essential Oils and Anti-Inflammatory Activity. AB - This review is aimed at presenting relevant information on the therapeutic potential of essential oil sesquiterpenes with anti-inflammatory activity. The data reviewed provide a basis for seeking new anti-inflammatory drugs from natural products that do not exhibit the undesirable side effects often displayed by anti-inflammatory drugs. In this review the experimental models, possible mechanisms of action, and chemical structures of 12 sesquiterpenes are presented. PMID- 26669123 TI - The Interaction of Alpha-synuclein with Membranes and its Implication in Parkinson's Disease: A Literature Review. AB - Alpha-synuclein belongs to the class of intrinsically disordered proteins lacking a well-folded structure under physiological conditions. The conversion of alpha synuclein from a soluble monomer to an insoluble fibril may underlie the neurodegeneration associated with Parkinson's disease (PD). Although the exact mechanism of alpha-synuclein toxicity is still unknown, it has been proposed that alpha-synuclein disturbs membrane structure, leading to increased membrane permeability and eventual cell death. This review highlights the significant role played by fluorescence techniques in unraveling the nature of interactions between alpha-synuclein and membranes and its implications in PD. PMID- 26669124 TI - Herbal Supplements and Hepatotoxicity: A Short Review. AB - Herbal products have gained popularity over the past few decades. The reasons attributed to the rise in popularity are cheaper costs, easy availability, patient compliance and fewer side effects. However, liver toxicity following consumption of herbal remedies is on the increase. Thus, there is an urgent need to understand the mechanism of action of the herbal supplements on the liver. Occasionally, herbal supplements may also interact with conventional drugs. The present review focusses on a few herbs such as Aloe barbadensis, Atractylis gummifera, Centella asiatica, Mitragyna speciosa, Morinda citrifolia, Larea tridentata, Symphytum officinale, Teucrium chamaedrys and Xanthium strumarium, which are reported to cause hepatotoxicity in humans and animals. Prior knowledge on hepatotoxicity caused by herbs may be beneficial for clinicians and medical practitioners. PMID- 26669125 TI - Vibrational Circular Dichroism: Recent Advances for the Assignment of the Absolute Configuration of Natural Products. AB - Vibrational circular dichroism (VCD) emerged during the last decade as a reliable tool for the absolute configuration (AC) determination of organic compounds. The principles, instrumentation, and methodology applied prior to early 2013 were recently reviewed by us. Since VCD is a very dynamic field, the aim of this review is to update VCD advances for the AC assignment of terpenoids, aromatic compounds, alkaloids, and other natural products for the 2013-2014 period, when VCD was applied to the AC assignment of some 70 natural products. In addition, although discovered in 2012, a brief introduction to the VCD exciton coupling approach and its applications in natural products AC assignment is presented. PMID- 26669126 TI - [Expansion of the hospital communities on the eve of the Revolution in the current central region]. PMID- 26669127 TI - [Vendome and its hospital during the war of 14-18]. PMID- 26669128 TI - [Orleans hospitals. Their history, their heritage]. PMID- 26669129 TI - [Hospitals and pilgrims in the middle ages Issoudun, a Hotel-Dieu on the routes of Compostela? The story distorted by Compostela]. PMID- 26669130 TI - [Family-based therapeutic shelters for the care of patients with mental disorders in Dun-sur-Auron]. PMID- 26669131 TI - [The hospital as seen by writers]. PMID- 26669132 TI - [The beginnings of the Charity Hospital (Paris)]. PMID- 26669133 TI - [Saint-Robert, old asylum for the mentally ill. Reconstruction campaign in the specialized hospital center Alpes-Isere: revisiting the history of the creation of the Saint-Robert old asylum for the mentally ill]. PMID- 26669134 TI - [Recent Development of Atomic Spectrometry in China]. AB - As an important part of modern analytical techniques, atomic spectrometry occupies a decisive status in the whole analytical field. The development of atomic spectrometry also reflects the continuous reform and innovation of analytical techniques. In the past fifteen years, atomic spectrometry has experienced rapid development and been applied widely in many fields in China. This review has witnessed its development and remarkable achievements. It contains several directions of atomic spectrometry, including atomic emission spectrometry (AES), atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), X-ray fluorescence spectrometry (XRF), and atomic mass spectrometry (AMS). Emphasis is put on the innovation of the detection methods and their applications in related fields, including environmental samples, biological samples, food and beverage, and geological materials, etc. There is also a brief introduction to the hyphenated techniques utilized in atomic spectrometry. Finally, the prospects of atomic spectrometry in China have been forecasted. PMID- 26669135 TI - [Studies on Cancer Diagnosis by Using Spectroscopy Combined with Chemometrics]. AB - Studies on cancer diagnosis using various spectroscopic methods combined with chemometrics are briefly reviewed. Elemental contents in serum samples were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES), bidirectional associative memory (BAM) networks were used to establish diagnosis models for the relationships between elemental contents and lung cancer, liver cancer, and stomach cancer, respectively. Near infrared spectroscopy (NIRS) is a non-destructive detection technology. Near infrared spectra of endometrial carcinoma samples were determined and spectral features were extracted by chemoometric methods, a fuzzy rule-based expert system (FuRES) was used for establishing diagnosis model, satisfactory results were obtained. We also proposed a novel variable selection method based on particle swarm optimization (PSO) for near infrared spectra of endometrial carcinoma samples. Spectra with optimized variable were then modeled by support victor machine (SVM). Terahertz technology is an emerging technology for non-destructive detection, which has some unique characteristics. Terahertz time domain spectroscopy (THz-TDS) was used for cervical carcinoma measurement. Absorption coefficients were calculated from the measured time domain spectra and then processed with derivative, orthogonal signal correction (PC-OSC) to reduce interference components, and then fuzzy rule-based expert system (FuRES), fuzzy optimal associative memory (FOAM), support victor machine (SVM), and partial least squares discriminant analysis (PLS-DA) were used for diagnosis model establishment. The above results provide useful information for cancer occurring and development, and provide novel approaches for early stage diagnosis of various cancers. PMID- 26669136 TI - [Simultaneous Determination of Sn and S in Methyltin Mercaptide by Microwave Assisted Acid Digestion and ICP-OES]. AB - Methyltin mercaptide is widely used as one of the best heat stabilizer in the polyvinylchloride (PVC) thermal processing due to its excellent stability, good transparency, high compatibility and weather resistance. The content of sulfur and tin significantly affects its quality and performance, so it is of great significance to develop an analytical method for the simultaneous determination of sulfur and tin. Inductively coupled plasma atomic emission spectrometry (ICP OES) has been a powerful analytical tool for a myriad of complex samples owing to its advantages of the low detection limits, rapid and precise determinations over wide dynamic ranges, freedom from chemical inter-element interferences, the high sample throughput and above all, simultaneous multi-elements analysis. Microwave technique as a well-developed method for sample preparation can dramatically reduce the digestion time and the loss of volatile elements compared with the traditional open digestion. Hereby, a microwave-assisted acid digestion (MW-AAD) procedure followed by inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis was developed for the simultaneous determination of Sn and S in methyltin mercaptide. This method has the advantages of simplicity, rapidness, good accuracy, green and less use of samples. Parameters affecting the MW-AAD such as the digestion solution and digestion time were optimized by using a chemical analyzed reference sample (DX-181) to attain tin and sulfur quantitative recoveries. HNO3-HCl-HClO4 (v/v/v=9:3:1) and 10 min were the optimum digestion solution and digestion time, respectively. Under optimum conditions, the standard addition method and the standard calibration curve method were both been used to detect Sn and S in DX-181. There was no significant difference between two methods and the relative deviations to the chemical analysis values were both less than 2%. Additionally, the accuracy of the MW-AAD method was examined by analyzing three methyltin mercaptide samples (DX-181, DX-990, DX-960). The results were satisfactory with the relative deviations (<3%) and the recoveries of standard addition (99%~102%). PMID- 26669137 TI - [Novel Hyphenated Techniques of Atomic Spectrometry for Metal Species Interaction with Biomolecules]. AB - Trace metals may be adopted by biological systems to assist in the syntheses and metabolic functions of genes (DNA and RNA) and proteins in the environment. These metals may be beneficial or may pose a risk to humans and other life forms. Novel hybrid techniques are required for studies on the interaction between different metal species and biomolecules, which is significant for biology, biochemistry, nutrition, agriculture, medicine, pharmacy, and environmental science. In recent years, our group dwells on new hyphenated techniques based on capillary electrophoresis (CE), electrothermal atomic absorption spectrometry (ETAAS), and inductively coupled plasma mass spectroscopy (ICP-MS), and their application for different metal species interaction with biomolecules such as DNA, HSA, and GSH. The CE-ETAAS assay and CE-ICP-MS assay allow sensitively probing the level of biomolecules such as DNA damage by different metal species and extracting the kinetic and thermodynamic information on the interactions of different metal species with biomolecules, provides direct evidences for the formation of different metal species--biomolecule adducts. In addition, the consequent structural information were extracted from circular dichroism (CD) and X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The present works represent the most complete and extensive study to date on the interactions between different metal species with biomolecules, and also provide new evidences for and insights into the interactions of different metal species with biomolecules for further understanding of the toxicological effects of metal species. PMID- 26669138 TI - Simultaneous Determination of Se and Te in Ores by HG-AFS After Online Preconcentration with Nano-TiO2 Immobilized on Silica Gel. AB - A simple, sensitive and interference-free method was established for simultaneous determination of trace selenium and tellurium in ore samples by HG-AFS, by using nano-TiO2 immobilized on a silica gel packed microcolumn for online preconcentration. Selenium and tellurium were selectively adsorbed to the microcolumn in acidic condition and then completely eluted with 2% (m/v) NaOH solution. The experimental conditions for hydride generation, adsorption, elution and potential interference were investigated in detail. Under the optimum conditions, the detection limits of selenium and tellurium by the proposed method with 180 s sampling time were 4.0 and 3.6 ng . L(-1), with sensitivity enhancement of 20- and 13-fold compared to conventional hydride generation method, respectively. The relative standard deviation (RSD, n=5) of this method for 1 MUg . L(-1) Se(IV) and Te(IV) were 0.7% and 2.3%, respectively. This method was applied to determination of selenium and tellurium in several ore samples. PMID- 26669139 TI - [Determination of Trace Elements in Marine Cetaceans by ICP-MS and Health Risk Assessment]. AB - The liver, kidney and muscle samples from seven cetaceans were digested by microwave digestion, and trace elements amounts of V, Cd, Cu, Zn, As, Cr, Ni, Mn, Se, Hg and Pb were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the health risk assessment for Zn, Cu, Cd, Hg, Se in the liver was conducted. The results of international lobster hepatopancreas standard (TORT-2) showed acceptable agreement with the certified values, and the relative standard deviation (RSD) of eleven kinds of trace elements were less than 3.54%, showing that the method is suitable for the determination of trace elements in cetaceans. The experimental results indicated that different tissues and organs of the dolphins had different trace elements, presenting the tissue specificity. There is a certain inter-species difference among different dolphins about the bioaccumulation ability of the trace elements. The distribution of trace elements in whales presented a certain regularity: the contents of most elements in liver, kidney were much higher than the contents of muscle tissues, Cu, Mn, Hg, Se, and Zn exhibit the higher concentrations in liver, while Cd was mainly accumulated in kidney. And according to the health risk assessment in liver, the exceeding standardrate of selenium and copper in seven kinds of whales was 100%, suggesting that these whales were suffering the contamination of trace elements. The experimental results is instructive to the study of trace elements in cetaceans, while this is the first report for the concentrations in organs of Striped dolphin, Bottlenose dolphin, Fraser's Dolphin and Risso's dolphin in China, it may provide us valuable data for the conservation of cetaceans. PMID- 26669140 TI - [Microsecond Pulsed Hollow Cathode Lamp as Enhanced Excitation Source of Hydride Generation Atomic Fluorescence Spectrometry]. AB - The spectral, electrical and atomic fluorescence characteristics of As, Se, Sb and Pb hollow cathode lamps (HCLs) powered by a laboratory-built high current microsecond pulse (HCMP) power supply were studied, and the feasibility of using HCMP-HCLs as the excitation source of hydride generation atomic fluorescence spectrometry (HG-AFS) was evaluated. Under the HCMP power supply mode, the As, Se, Sb, Pb HCLs can maintain stable glow discharge at frequency of 100~1000 Hz, pulse width of 4.0~20 MUs and pulse current up to 4.0 A. Relationship between the intensity of characteristic emission lines and HCMP power supply parameters, such as pulse current, power supply voltage, pulse width and frequency, was studied in detail. Compared with the conventional pulsed (CP) HCLs used in commercial AFS instruments, HCMP-HCLs have a narrower pulse width and much stronger pulse current. Under the optimized HCMP power supply parameters, the intensity of atomic emission lines of As, Se, Sb HCLs had sharp enhancement and that indicated their capacity of being a novel HG-AFS excitation source. However, the attenuation of atomic lines and enhancement of ionic lines negated such feasibility of HCMP-Pb HCL. Then the HG-AFS analytical capability of using the HCMP-As/Se/Sb HCLs excitation source was established and results showed that the HCMP-HCL is a promising excitation source for HG-AFS. PMID- 26669141 TI - [Preconcentration of Trace Cu(II) in Water Samples with Nano-Sized ZnO and Determination by GFAAS]. AB - The content of copper in natural water is very low, and direct determination is difficult. Therefore, it is very meaningful for the combination of efficient separation-enrichment technology and highly sensitive detection. Based on the high adsorption capacity of Cu(II) onto nano-sized ZnO, a novel method by using nano-sized ZnO as adsorbent and graphite furnace atomic absorption spectrometry as determination means was in this work. The adsorption behaviors of Cu(II) on nano-sized ZnO was studied. Effects of acidity, adsorption equilibrium time, adsorbent dosage and coexisting ions on adsorption rates were investigated. The results showed that the adsorption efficiency was above 95% in a pH range from 3.0 to 7.0. Compared with other adsorbents for trace element enrichment such as activated carbon, nano-sized TiO2 powder, the most prominent advantage is nano sized ZnO precipitate with the concentrated element can directly dissolved in HCl solution without any filtration and desorption process can directly analyzed by graphite furnace atomic absorption spectrometry or inductively coupled plasma atomic emission spectrometry. Compared with colloid nano materials, nano-sized ZnO is the true solution after dissolving have small matrix effect and viscosity more suitable for graphite furnace atomic absorption spectrometry or inductively coupled plasma atomic emission spectrometry detection. The proposed method possesses low detection limit (0.13 MUg . L(-1)) and good precision (RSD=2.2%). The recoveries for the analysis of environmental samples were in a rang of 91.6%~92.6% and the analysis results of certified materials were compellent by using the proposed method. PMID- 26669142 TI - Absorption and Fluorescence Properties of Chromophoric Dissolved Organic Matter Produced by Algae. AB - Four kinds of diatom (Chaetoceros curvisetus, Phaeodactylum tricornutum, Nitzschia closterium f. minutissima and Navicula halophile) and two kinds of dinoflagellates (Prorocentrum donghaiense and Gymnodinium) were cultured under laboratory conditions. Variations of optical properties of chromophoric dissolved organic matter (CDOM) were studied with absorption and fluorescence excitation emission matrix spectroscopy(EEM) during growth of marine microalgae in incubation experiment. Absorption spectrum revealed absorption coefficient a(355) (CDOM absorption coefficients at 355 nm) of 6 kinds of marine microalgae above increased by 64.8%, 242.3%, 535.1%, 903.2%, 836% and 196.4%, respectively. Simultaneously, the absorption spectral slope (Sg), determined between 270 and 350 nm, representing the size of molecular weight of CDOM and humic-like composition, decreased by 8.7%, 34.6%, 39.4%, 53.1%, 46.7%, and 35.7%, respectively. Applying parallel factor analysis (PARAFAC) together with EEM got four components of CDOM: C1(Ex/Em=350(260) nm/450 nm), C2 (Ex/Em=260(430) nm/525 nm), C3 (Ex/Em=325 nm/400 nm) and C4(Ex/Em=275 nm/325 nm), which were relative to three humic-like and one protein-like fluorescent components of Nitzschia closterium f. minutissima and Navicula halophile. In incubation experiment, fluorescence intensity of these four components during growth of Nitzschia closterium f. minutissima increased by, respectively, 8.68, 24.9, 7.19 and 39.8 times, and those of Navicula halophile increased by 2.64, 0.07, 4.39 and 12.4 times, respectively. Significant relationships were found between the fluorescence intensity of four components of CDOM, a(355) and Sg. All results demonstrated that both content and molecular weight of CDOM produced by diatom and dinoflagellate studied in incubation experiment increased, but these two parameters changed more obviously of the diatom than those of dinoflagellate; the proportion of humic-like components in the composition of CDOM also increased clearly with the growth of marine microalgae, but protein-like fluorescent component had only a slow growth. Furthermore, the absorption spectrum of CDOM produced by different species of algae changed obviously and the relative composition fluorescence intensity of CDOM produced by different microalgae were found to vary among different composition from EEM, which suggested CDOM produced by different microalgae make quite different contributions to CDOM in natural seawater. PMID- 26669143 TI - Analysis of Aluminum Dust Cloud Combustion Using Flame Emission Spectroscopy. AB - In this study, aluminum flame analysis was researched in order to develop a measurement method for high-energy-density metal aluminum dust cloud combustion, and the flame temperature and UV-VIS-IR emission spectra were precisely measured using a spectrometer. Because the micron-sized aluminum flame temperature was higher than 2400 K, Flame temperature was measured by a non-contact optical technique, namely, a modified two-color method using 520 and 640 nm light, as well as by a polychromatic fitting method. These methods were applied experimentally after accurate calibration. The flame temperature was identified to be higher than 2400 K using both methods. By analyzing the emission spectra, we could identify AlO radicals, which occur dominantly in aluminum combustion. This study paves the way for realization of a measurement technique for aluminum dust cloud combustion flames, and it will be applied in the aluminum combustors that are in development for military purposes. PMID- 26669144 TI - [Synthesis of Magnetic Metal Organic Framework Fe3O4@NH2-MIL-53 (Al) Materials and Application to the Adsorption of Lead]. AB - Metal organic framework, a novel class of organic inorganic hybrid functional materials, has been widely used in the fields of gas adsorption, catalysis, separation, and biological medicine due to its large specific surface area, diverse structural, and adjustable channel. In this work, a new amine functionalized magnetic metal-organic framework material was synthesized. Nano Fe3O4 was prepared by a solvothermal method, after which polyvinyl pyrrolidone was employed to modify Fe3O4. Finally, amino groups were introduced to prepare Fe3O4@NH2-MIL-53(Al). The crystal structure and functional groups of the material were characterized by means of X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FT-IR). Combined with flame atomic absorption spectroscopy (FAAS), the adsorption of lead by the magnetic adsorbent was investigated. The magnetic adsorbent possesses high adsorption capacity because of the large specific surface area of Fe3O4@NH2-MIL-53(Al) and the coordination between amino group and lead. Experimental conditions affecting the adsorption percentage were discussed and the experimental operation parameters were optimized (pH value of 6.0 and adsorption time of 120 min). Kinetics and thermodynamics studies were conducted for the adsorption process. Langmuir/Freundlich and pseudo-first order/pseudo-second-order models were applied to analyze the experimental data. Thermodynamic functions, i. e., changes of Gibbs energy, entropy, and enthalpy, were calculated from temperature experiments. In addition, the regeneration of the adsorbent was considered with hydrochloric acid as the desorption solution. Several adsorption and desorption experiments were carried out, illustrating that the Fe3O4@NH2-MIL-53(Al) adsorbent can be used repeatedly. PMID- 26669145 TI - [Mass Spectrometric Methods for Colorative Mechanism Analysis of Yaozhou Porcelain Glaze]. AB - An in-house-built femtosecond laser ionization time-of-flight mass spectrometry (fs-LI-TOFMS) has been applied to the multi-elemental analysis of porcelain glaze from Yaozhou kiln. The samples are selected representing products of different dynasties, including Tang, Five, Song, Jin, and Ming Dynasty. For exploring the colorative mechanism of Yaozhou porcelain through the elemental analysis of the glaze, the effects of all potential coloring elements, especially transition elements, were considered. There was a speculation that the typical Co-Cr-Fe-Mn recipe was used in the fabrication of Yaozhou black glaze; the low content of Fe and high content of Ni resulted in the porcelain of white glaze; an increase content of P could lead the porcelain to be yellow-glazed. Undoubtedly, this research is an important supplement to the study of the colorative mechanism of the Yaozhou porcelain system. PMID- 26669146 TI - [The Progress on Cataluminescence-Based Analytical System]. AB - Cataluminescence (CTL) is a phenomenon of light radiation generated when analyte moleculars were oxidized by catalyst. In the past few decades, CTL has developed rapidly and become a promising detection technique, especially in gas sensing, and has attracted much attention of researchers for its potential versatile applications in emission control, public safety, and environmental protection. The analytical system based on CTL has low detection limit, high sensitivity and simple instrument which easy to operate, which shows huge advantages in the detection of inorganic gases and volatile organic compounds. The library of sensing materials has been greatly enriched to thousands kinds, which contains metals, metal/non-metal oxides, sulfide, metal salts, organic compounds, ceramic, glass and other types of materials; Composite materials have been developed; The decreasing of material dimensions to nanoscale provided new opportunities for its development; The morphology of material has also been explored. Some novel hyphenated techniques based on CTL coupled to other techniques including preconcentration/sepration, nebulization, plasma have been developed, as well as some new CTL technique including static CTL, cyclic CTL and ect. Thanks to development of sensing material and the appearance of these novel techniques, the selectivity and sensitivity of CTL system has been improved, and the range of CTL application has been extended. In this article, the progress made in the field of cataluminescence, especially in latest developments of analytical applications were reviewed. The catalysts used in CTL, the recent novel CTL techniques were sumerized. The future of the cataluminescence was also forecasted. PMID- 26669147 TI - [Study on the Effects of Different Ferron System, Ferron Solubility, Experimental Temperature and Other Factors for the Accurate Determination of Mononuclear Aluminum Concentration in Aqueous Solution]. AB - Ferron colorimetric method has been widely used in aluminum speciation analysis. However, some important factors that may affect the accurate determination of mononuclear Al concentration have not been studied yet. Using molar absorption coefficient epsilon as a key indicator, the critical issues in Al-Ferron coloring reaction system have been investigated experimentally in this paper, including different Ferron system, Ferron solubility, experimental temperature, ionic strength and the reference system. The results show that three vital factors (different Ferron colorimetric system, Ferron solubility and experimental temperature) would significantly affect the accurate measurement of mononuclear Al concentration; whereas, other two factors like ionic strength and the reference have litter influence. Base on our experimental results and statistic analysis of relevant important literatures, we suggest that optimizing colorimetric conditions and standardizing operational procedures should be paid much more attention in Ferron colorimetric assay in order to obtain the accurate measurement results. PMID- 26669148 TI - [High Precision Identification of Igneous Rock Lithology by Laser Induced Breakdown Spectroscopy]. AB - In the field of petroleum exploration, lithology identification of finely cuttings sample, especially high precision identification of igneous rock with similar property, has become one of the geological problems. In order to solve this problem, a new method is proposed based on element analysis of Laser-Induced Breakdown Spectroscopy (LIBS) and Total Alkali versus Silica (TAS) diagram. Using independent LIBS system, factors influencing spectral signal, such as pulse energy, acquisition time delay, spectrum acquisition method and pre-ablation are researched through contrast experiments systematically. The best analysis conditions of igneous rock are determined: pulse energy is 50 mJ, acquisition time delay is 2 MUs, the analysis result is integral average of 20 different points of sample's surface, and pre-ablation has been proved not suitable for igneous rock sample by experiment. The repeatability of spectral data is improved effectively. Characteristic lines of 7 elements (Na, Mg, Al, Si, K, Ca, Fe) commonly used for lithology identification of igneous rock are determined, and igneous rock samples of different lithology are analyzed and compared. Calibration curves of Na, K, Si are generated by using national standard series of rock samples, and all the linearly dependent coefficients are greater than 0.9. The accuracy of quantitative analysis is investigated by national standard samples. Element content of igneous rock is analyzed quantitatively by calibration curve, and its lithology is identified accurately by the method of TAS diagram, whose accuracy rate is 90.7%. The study indicates that LIBS can effectively achieve the high precision identification of the lithology of igneous rock. PMID- 26669149 TI - [A Terahertz Spectral Database Based on Browser/Server Technique]. AB - With the solution of key scientific and technical problems and development of instrumentation, the application of terahertz technology in various fields has been paid more and more attention. Owing to the unique characteristic advantages, terahertz technology has been showing a broad future in the fields of fast, non damaging detections, as well as many other fields. Terahertz technology combined with other complementary methods can be used to cope with many difficult practical problems which could not be solved before. One of the critical points for further development of practical terahertz detection methods depends on a good and reliable terahertz spectral database. We developed a BS (browser/server) -based terahertz spectral database recently. We designed the main structure and main functions to fulfill practical requirements. The terahertz spectral database now includes more than 240 items, and the spectral information was collected based on three sources: (1) collection and citation from some other abroad terahertz spectral databases; (2) collected from published literatures; and (3) spectral data measured in our laboratory. The present paper introduced the basic structure and fundament functions of the terahertz spectral database developed in our laboratory. One of the key functions of this THz database is calculation of optical parameters. Some optical parameters including absorption coefficient, refractive index, etc. can be calculated based on the input THz time domain spectra. The other main functions and searching methods of the browser/server based terahertz spectral database have been discussed. The database search system can provide users convenient functions including user registration, inquiry, displaying spectral figures and molecular structures, spectral matching, etc. The THz database system provides an on-line searching function for registered users. Registered users can compare the input THz spectrum with the spectra of database, according to the obtained correlation coefficient one can perform the searching task very fast and conveniently. Our terahertz spectral database can be accessed at http://www.teralibrary.com. The proposed terahertz spectral database is based on spectral information so far, and will be improved in the future. We hope this terahertz spectral database can provide users powerful, convenient, and high efficient functions, and could promote the broader applications of terahertz technology. PMID- 26669150 TI - [Glow Discharge Characteristics of Hollow Needle-Plate Electrode in Atmospheric Pressure Argon]. AB - Atmosphere pressure uniform plasma has the broad application prospect in the industrial field. Using hollow needle cathode-plate anode device excited by direct-current voltage, a uniform and stable glow discharge is generated at atmospheric pressure in ambient air with argon used as working gas. The influence of the experimental parameters (including gas flow rate and the gas gap width) on discharge has been investigated by optical method. It can be found that a glow discharge plasma column can bridge the two electrodes. The plasma column is uniform, and no filaments can be discerned. Near the plate electrode, the diameter of the plasma column is largest of all positions. The maximal diameter of the plasma column increases with increasing the discharge current or the gas flow rate. Through electrical method, the voltage-current characteristic has been investigated. It has been found that the discharge voltage decreases with increasing the current which is similar with the characteristic of glow discharge in low pressure. It increases with increasing the gas gap width or the gas flow rate. By analyzing the optical emission spectrum scanning from 330 to 450 nm emitted from the direct-current glow discharge, the molecular vibrational temperature and the intensity ratio of spectral lines I391.4/I337.1 have been investigated as functions of the gas flow rate and gas gap width. Results indicate that both the vibrational temperature and the intensity ratio of spectral lines I391.4/I337.1 decrease with increasing the gas flow rate or the gas gap width. In addition, the molecular vibrational temperature and the intensity ratio of spectral lines I391.4/I337.1 have been investigated in spatial resolution along the direction of gas flow (plasma column axial), and give a qualitative analysis as well. It is found that the vibrational temperature and the average electron energy increase with increasing the distance from the hollow needle cathode. These results are important to the industrial applications of glow discharge. PMID- 26669151 TI - [Study on Spectral Characteristics of Two Kinds of Home-Made Novel Yb-Doped Fluoride Laser Crystals]. AB - Yb-doped fluoride crystals are of important another Yb-doped laser materials besides Yb-doped oxide, which are becoming one of interests for developing tunable lasers and ultrafast lasers. In this paper, the systematic and contrastive experiments of the optical spectral characteristics are presented for two types of home-made novel Yb-doped fluoride laser crystals, namely, Yb-doped CaF2-SrF2 mixed crystal and co-doped Yb, Y:CaF2 single crystal. The fluorescent features of Yb-doped CaF2-SrF2 mixed crystal and co-doped Yb, Y:CaF2 single crystal are apparently different by the fluorescence experiment. The physical mechanism of these fluorescence spectra were analyzed and proposed. The influence of doping concentrations of active Yb(3+) ions or co-doping Y ions on the absorption of Yb-doped CaF2-SrF2 mixed crystal and co-doped Yb, Y:CaF2 single crystal was experimentally investigated, and the optimal values of doping concentrations of active Yb(3+) ions or co-doping Y ions in the two types of fluoride laser crystals were obtained. Continuous-wave laser operation for the two novel fluoride laser crystals has been achieved in three-mirror-folded resonator using a laser diode as the pump source. Therein, the laser operation for the co-doped Yb, Y:CaF2 crystal is demonstrated for the first time. For the two types of fluoride laser crystals (four samples), the input-output power relational curves, the optical slope efficiencies and the laser spectra were demonstrated by the laser experiments. By comparisons between the two types of fluoride laser crystals in the absorbability, fluorescence and laser spectra, laser threshold and slope efficiency of the continuous-wave laser operation, the results show that the best one of the four samples in spectral and laser characteristics is co-doped 3at%Yb, 6at% Y:CaF2 single crystal, which has an expected potential in the application. The research results provide available references for improving further laser performance of Yb-doped fluoride crystals. PMID- 26669152 TI - [Characterization of Nd Doped Films Prepared by Femtosecond Pulsed Laser Deposition]. AB - Thin films of Nd:YAG and Nd:Glass were prepared on Si(100) substrate by pulsed laser deposition technology. The morphology of film surface and cross section, composition, absorption spectrum and photoluminescence (PL) spectra of films were investigated by scanning electron microscope (SEM), energy disperse spectroscopy (EDS), Fourier transform infrared spectrometer (FTIR), optical parametric oscillator (OPO) and grating spectrometer. The results show that both Nd:YAG films and Nd:Glass films grown on the substrates at room temperature are amorphous. Nd:YAG films grown by PLD contain Nd element with 0.15 at. % stoichiometric proportion. The absorption spectrum of bulk Nd:YAG target rather than deposited films exhibit two absorption peaks at 750 and 808 nm. There are no evident peaks in the photoluminescence spectra curve of Nd:YAG films. However, the photoluminescence spectra of Nd:Glass films with two sharp peaks at the wavelength of 877 and 1064 nm are observed. It indicates that Nd is doped into glass host as optically active Nd(3+) ions when Nd:Glass films grow at room temperature. But for Nd:YAG films, Nd don't incorporate into YAG host as Nd(3+) ions. PMID- 26669153 TI - [Application of Three Dimensional Confocal Micro X-Ray Fluorescence Technology Based on Polycapillary X-Ray Lens in Analysis of Rock and Mineral Samples]. AB - Confocal three dimensional (3D) micro X-ray fluorescence (XRF) spectrometer based on a polycapillary focusing X-ray lens (PFXRL) in the excitation channel and a polycapillary parallel X-ray lens (PPXRL) in the detection channel was developed. The PFXRL and PPXRL were placed in a confocal configuration. This was helpful in improving the signal-to-noise ratio of the XRF spectra, and accordingly lowered the detection limitation of the XRF technology. The confocal configuration ensured that only the XRF signal from the confocal micro-volume overlapped by the output focal spot of the PFXRL and the input focal spot of the PPXRL could be detected by the detector. Therefore, the point-to-point information of XRF for samples could be obtained non-destructively by moving the sample located at the confocal position. The magnitude of the gain in power density of the PFXRL was 10(3). This let the low power conventional X-ray source be used in this confocal XRF, and, accordingly, decreased the requirement of high power X-ray source for the confocal XRF based on polycapillary X-ray optics. In this paper, we used the confocal 3D micro X-ray fluorescence spectrometer to non-destructively analyzed mineral samples and to carry out a 3D point-to-point elemental mapping scanning, which demonstrated the capabilities of confocal 3D micro XRF technology for non destructive analysis elements composition and distribution for mineral samples. For one mineral sample, the experimental results showed that the area with high density of element of iron had high density of copper. To some extent, this reflected the growth mechanisms of the mineral sample. The confocal 3D micro XRF technology has potential applications in such fields like the analysis identification of ore, jade, lithoid utensils, "gamble stone" and lithoid flooring. PMID- 26669154 TI - [The Non-Destructive Analysis of Some Ancient Jade Artifacts Unearthed from Henan Province by a Variety of Optical Techniques]. AB - A total of 14 pieces of ancient jade artifact unearthed from Henan Province were non-destructively analyzed by means of a portable X-ray fluorescence spectrometer (pXRF), laser Raman spectroscopy (portable and mobile) and optical coherence tomography (OCT) technology, comprehensively. The raw materials of ancient jade artifacts could be determined accurately through the combination of pXRF and portable Raman spectrometer in a short time. With the advantages of small size and easy-operation, these two instruments are suitable to in situ non-destructive analysis of ancient jade artifacts. The results of the pXRF shows that these ancient jade artifacts can be divided into 6 categories such as rich in Si Al K, rich in Ca, rich in Si Ca, rich in Si Mg, rich in Si, rich in Ca P. Their main phases have been successfully identified by the portable Raman spectrometer. In the lab, the mobile confocal laser Raman spectrometer, which help us find the Raman vibration peak of [OH] in the tremolite jade, is used to make up the disadvantages of the portable Raman spectrometer such as lower spectral resolution, lower accuracy and narrower measuring range. We can use the OCT to analyze the transparency, fiber fineness and inclusion etc. of the jade artifacts. The confocal laser Raman spectroscopy combined with OCT is used to analyze 2 containing inclusion of tremolite jade samples. OCT image can visually display the distribution characteristics of the inclusion in these 2 samples. Confocal laser Raman spectroscopy can accurately locate the sample surface of inclusion, then we can observe the micro morphology and analyze its phase. The results show that the black inclusion is graphite. This work is very significant to study the geographical origin of jade. Through the study we find, the use of pXRF, laser Raman spectroscopy (portable and mobile) and OCT can be achieved on the identification and analysis of cultural relic's phase composition and texture feature and meet the basic requirements of field archaeological work analysis. PMID- 26669155 TI - [Factors Analysis for CO2 Retrieval from the Ground-Based Hyperspectral Measurements in the Short Wave Infrared]. AB - Ground-based CO2 inversion accuracy determines the understanding of CO2 source and sink. However the study about factors affecting ground-based CO2 inversion. In order to improve CO2 inversion accuracy, the effects from aerosol, spectral shift, spectral band selection, spectrometer response function type, half width and truncation error have been analyzed by using radiative transfer model. The results show that: (1) the multiple scattering of aerosol can be ignored when instrument field of view is less than 1.5 degrees and aerosol optical depth is less than 0.5. (2) The inversion results are smaller when there are spectral offsets. The inversion errors increase nonlinear with spectral offsets. And the higher the spectral resolution, the larger the effect of spectral shift. (3) Different spectral bands have various average signal-to-noise ratio, selecting channels with appropriate signal-to-noise ratio and enhancing instrument signal to-noise ratio can reduce the effect of instrument noise. (4) The higher the instrument resolution, the more important the degree of accuracy of instrument line function for simulated spectrum. Therefore, for hyper-spectral observation, the constancy of environmental temperature is key of acquiring high precision inversion results. (5) For over-high spectral resolution, simulated spectrum is anamorphic due to crosstalk effect. Therefore the crosstalk effect must be considered when the spectrometer resolution is advanced. PMID- 26669156 TI - [Study on Extraction Methods of Characteristic Wavelength of Visible Near Infrared Spectroscopy Used for Sugar Content of Hetao Muskmelon]. AB - Hetao muskmelon is a unique fruit in the hetao area of northwest china, which has been loved by consumers. Sugar content is the important indicator of measuring the quality and mature of muskmelons. This research uses Maya 2000 pro portable spectrometer and PR-101alpha portable digital refractometer to get spectrum and sugar content values of "jinhongbao" muskmelon, researches the effect of different extraction methods of characteristic wavelength (stepwise multiple linear regression (SMLR), interval partial least squares(iPLS), backward interval partial least squares (biPLS) and synergy interval partial least squares (siPLS)) on model accuracy and prediction results. The results show: using biPLS method on extraction of characteristic wavelength will the full spectrum evenly divided into 20 subintervals, the PLS factors of 14, when removing 8 subintervals, and choosing the wavelength variable numbers of 218, getting the biPLS model is best, RMSE of corresponding calibration and prediction models is 0.9961 and 1.18. So using the biPLS method of extraction on spectrum wavelength could extract effectively the characteristic wavelengths of melon sugar content, increase the ability of model prediction, and achieve rapid detecting of sugar content about muskmelons. PMID- 26669157 TI - [A Study of the Relationship Among Genetic Distances, NIR Spectra Distances, and NIR-Based Identification Model Performance of the Seeds of Maize Iinbred Lines]. AB - This paper explored the relationship among genetic distances, NIR spectra distances and NIR-based identification model performance of the seeds of maize inbred lines. Using 3 groups (total 15 pairs) of maize inbred lines whose genetic distaches are different as experimental materials, we calculates the genetic distance between these seeds with SSR markers and uses Euclidean distance between distributed center points of maize NIR spectrum in the PCA space as the distances of NIR spectrum. BPR method is used to build identification model of inbred lines and the identification accuracy is used as a measure of model identification performance. The results showed that, the correlation of genetic distance and spectra distancesis 0.9868, and it has a correlation of 0.9110 with the identification accuracy, which is highly correlated. This means near-Infrared spectrum of seedscan reflect genetic relationship of maize inbred lines. The smaller the genetic distance, the smaller the distance of spectrum, the poorer ability of model to identify. In practical application, near infrared spectrum analysis technology has the potential to be used to analyze maize inbred genetic relations, contributing much to genetic breeding, identification of species, purity sorting and so on. What's more, when creating a NIR-based identification model, the impact of the maize inbred lines which have closer genetic relationship should be fully considered. PMID- 26669158 TI - [Quantitatively Determination of Available Phosphorus and Available Potassium in Soil by Near Infrared Spectroscopy Combining with Recursive Partial Least Squares]. AB - Soil available phosphorus (P) and available potassium (K) don't possess direct spectral response in the near infrared (NIR) region. They are predictable because of their correlation with spectrally active constituents (organic matter, carbonates, clays, water, etc.). Such correlation may of course differ between the soil sample sets. Therefore, the NIR calibration models with fixed structure are difficult to achieve good prediction performances for soil P and K. In this work, the method of recursive partial least squares (RPLS), which is able to update the model coefficients recursively during the prediction process, has been applied to improve the predictive abilities of calibration models. This work compared the performance of partial least squares regression (PLS), locally weighted PLS (LW-PLS), moving window LW-PLS (LW-PLS2) and RPLS for the measurement of soil P and K. The entire data set of 194 soil samples was split into calibration set and prediction set based on soil types. The calibration set was composed of 120 Anthrosols samples, while the prediction set included 29 Ferralsols samples, 23 Anthrosols samples and 22 Primarosols samples. The best prediction results were obtained by the RPLS model. The coefficient of determination (R2) and residual prediction deviation (RPD) were respectively 0.61, 0.76 and 1.60, 2.05 for soil P and K. The results indicate that RPLS is able to learn the information from the latest modeling sample by recursively updating the model coefficients. The proposed method RPLS has the advantages of wider applicability and better performance for NIR prediction of soil P and K compared with other methods in this work. PMID- 26669159 TI - [Near Infrared Spectroscopy of the Cretaceous Red Beds in Inner Mongolia Dongshengmiao]. AB - Take the cores and surface weathered soil from the Cretaceous red beds in the western of Dongshengmiao mine of Inner Mongolia and analysis with near-infrared spectroscopy. The result shows that near-infrared spectroscopy can identify mineral quickly through the characteristic absorption peaks of each group. The Cretaceous red beds in the western of Dongshengmiao mine is argillaceous cementation, it is mainly composed of quartz, feldspar, montmorillonite, illite, chlorite, muscovite etc, the mineral composition is mainly affected by the upstream source area. The clay mineral like montmorillonite water swelling and uneven drying shrinkage expands the original crack and creates new cracks, reduces its strength, which is the mainly reason of its disintegration. According to the composition of clay mineral, we speculate its weathering process is mainly physical weathering, the climate during the weathering is cold and dry. The results can not only improve the geological feature of the mining area, but also show that the near-infrared spectroscopy technology can analyze the mineral composition of soil and rock effectively on the basis of Mineral spectroscopy, which demonstrates the feasibility of the near-infrared spectroscopy can analyze minerals in soil and rock quickly, that shows the feasibility in geology study, provides new ideas for the future research of soil and rock. PMID- 26669160 TI - [Main Components of Xinjiang Lavender Essential Oil Determined by Partial Least Squares and Near Infrared Spectroscopy]. AB - This work was undertaken to establish a quantitative analysis model which can rapid determinate the content of linalool, linalyl acetate of Xinjiang lavender essential oil. Totally 165 lavender essential oil samples were measured by using near infrared absorption spectrum (NIR), after analyzing the near infrared spectral absorption peaks of all samples, lavender essential oil have abundant chemical information and the interference of random noise may be relatively low on the spectral intervals of 7100~4500 cm(-1). Thus, the PLS models was constructed by using this interval for further analysis. 8 abnormal samples were eliminated. Through the clustering method, 157 lavender essential oil samples were divided into 105 calibration set samples and 52 validation set samples. Gas chromatography mass spectrometry (GC-MS) was used as a tool to determine the content of linalool and linalyl acetate in lavender essential oil. Then the matrix was established with the GC-MS raw data of two compounds in combination with the original NIR data. In order to optimize the model, different pretreatment methods were used to preprocess the raw NIR spectral to contrast the spectral filtering effect, after analysizing the quantitative model results of linalool and linalyl acetate, the root mean square error prediction (RMSEP) of orthogonal signal transformation (OSC) was 0.226, 0.558, spectrally, it was the optimum pretreatment method. In addition, forward interval partial least squares (FiPLS) method was used to exclude the wavelength points which has nothing to do with determination composition or present nonlinear correlation, finally 8 spectral intervals totally 160 wavelength points were obtained as the dataset. Combining the data sets which have optimized by OSC-FiPLS with partial least squares (PLS) to establish a rapid quantitative analysis model for determining the content of linalool and linalyl acetate in Xinjiang lavender essential oil, numbers of hidden variables of two components were 8 in the model. The performance of the model was evaluated according to root mean square error of cross-validation (RMSECV), root mean square error of prediction (RMSEP). In the model, RESECV of linalool and linalyl acetate were 0.170 and 0.416, respectively; RM-SEP were 0.188 and 0.364. The results indicated that raw data was pretreated by OSC and FiPLS, the NIR-PLS quantitative analysis model with good robustness, high measurement precision; it could quickly determine the content of linalool and linalyl acetate in lavender essential oil. In addition, the model has a favorable prediction ability. The study also provide a new effective method which could rapid quantitative analysis the major components of Xinjiang lavender essential oil. PMID- 26669161 TI - [Feature Selection and Interpretation in Infrared Quantitative Models of Liquiritin and Glycyrrhizin in Radix Glycyrrhizae]. AB - Feature selection can improve the interpretation of the modeling variables to a certain extent by selecting variables from the complex spectra backgrounds. However, the improvement of models interpretation does not mean that the modeling variables have the exact physical or chemical significance. In this paper, We explore the relation between the chemical characteristics of target components and the spectrum variables selected with 3 kinds of variables selection methods which are moving window partial least squares regression (mwPLS), synergy interval partial least squares regression (siPLS) and competitive adaptive re weighted sampling (CARS), and compare the interpretation difference of the variables selected with the above variables selection methods. The results show that the variables selected with mwPLS accord with nu(phi)C=C of liquiritin and deltaCH3 or deltaCH2 of glycyrrhizin, which are the obvious spectra differences between the flavonoids and saponins in Radix Glycyrrhizae, and the variables selected with siPLS are the characteristic intervals combinations of the flavonoids or saponins in Radix Glycyrrhizae, which is the combination of nu(o)C=C, nu(o)C-O, nu(o)C-H of flavonoids or the combination of nuC-O vC-H, nuO H of saponins while the variables selected with CARS can better accord with most of the characteristic peaks from 1000 to 4000 cm(-1) of liquiritin or glycyrrhizin in Radix Glycyrrhizae, and the predict performance of the infrared quantitative model established on the spectroscopic variables selected with CARS can be improved. Therefore, most of the variables selected with CARS can be interpreted by the characteristic peaks in the infrared characteristic region of the target components, which is beneficial to improve the interpretation of the quantitative model. PMID- 26669162 TI - [Discrimination of Rice Syrup Adulterant of Acacia Honey Based Using Near Infrared Spectroscopy]. AB - At present, the rice syrup as a low price of the sweeteners was often adulterated into acacia honey and the adulterated honeys were sold in honey markets, while there is no suitable and fast method to identify honey adulterated with rice syrup. In this study, Near infrared spectroscopy (NIR) combined with chemometric methods were used to discriminate authenticity of honey. 20 unprocessed acacia honey samples from the different honey producing areas, mixed? with different proportion of rice syrup, were prepared of seven different concentration gradient? including 121 samples. The near infrared spectrum (NIR) instrument and spectrum processing software have been applied in the? spectrum? scanning and data conversion on adulterant samples, respectively. Then it was analyzed by Principal component analysis (PCA) and canonical discriminant analysis methods in order to discriminating adulterated honey. The results showed that after principal components analysis, the first two principal components accounted for 97.23% of total variation, but the regionalism of the score plot of the first two PCs was not obvious, so the canonical discriminant analysis was used to make the further discrimination, all samples had been discriminated correctly, the first two discriminant functions accounted for 91.6% among the six canonical discriminant functions, Then the different concentration of adulterant samples can be discriminated correctly, it illustrate that canonical discriminant analysis method combined with NIR spectroscopy is not only feasible but also practical for rapid and effective discriminate of the rice syrup adulterant of acacia honey. PMID- 26669163 TI - A Method to Obtain a Good Infrared Spectrum of the Wet Acetone Gas Sample without Any Drying Pretreatment. AB - Water vapor in the beam of a Fourier transform infrared (FTIR) spectrometer or/and in a gas cell is a major source of interference in the infrared measurement of a gas sample. In general, in order to eliminate the effect of water vapor, we have to completely remove these molecules before the measurement of any spectrum. Herein, we provide an approach to collect an IR spectrum of a gas (wet acetone) sample free from water vapor interference without any drying pretreatment. After dozens of scans, the air atmosphere in the sample compartment of the FTIR spectrometer will be slightly adjusted by small amounts of dry air or wet air (room air) depending on the property of water vapor lines (absorbance >0 or absorbance <0). Water vapor lines will then gradually disappear when the ensuing collection process is continued. The experiment results demonstrated that this method is a facile and very effective way to remove water vapor interference. Moreover, this method works still well for the measurement at 0.5 cm(-1) resolution, typically used in the gas infrared measurement. PMID- 26669164 TI - [Calibration Procedure of Laser Confocal Micro-Raman Spectrometer]. AB - As a common spectral characterization technique, Raman spectroscopy is widely used and has a specified calibration procedure. Based on laser confocal micro Raman spectrometer, in this paper, we briefly introduced the principle, configuration and main components of Raman spectrometer. In addition, the calibration procedures were also presented, with an emphasis on the calibration of spectrometer (spectrograph) and that of excitation laser wavelength. On the basis of conventional calibration method, a novel and more accurate method was proposed to obtain the actual excitation wavelength, that is, calibration at the point of Raman shift Deltanu=0. Using this novel calibration method of excitation wavelength, Raman frequency shift values of sulfur were measured, and compared with the standard values from American Society Testing and Materials (ASTM). As a result, the measured values after calibration were consistent with those ASTM values, which indicated that the calibration method is accurate. Thus, a more reasonable calibration procedure of the laser confocal micro-Raman spectrometer was provided. PMID- 26669165 TI - [Research on the Quantitative Analysis for In-Situ Detection of Acid Radical Ions Using Laser Raman Spectroscopy]. AB - Laser Raman spectroscopy as an in situ analytical technology can enable detailed investigation of the ocean environment. It is necessary to set up a quantitative analysis method based on laser Raman spectroscopy to understand the marine status in situ. In the laboratory investigations, varied concentration of HCO3(-), SO4(2 ) and coastal waters of Qingdao are taken as the samples, operating 532 nm of laser, using fiber optic probes to simulate detection mode in situ. Raman spectra are analyzed using the method of internal standard normalization, multiple linear regression (MLR), general Partial Least Squares (PLS) and PLS based on dominant factor respectively in data processing. It was found that correlation coefficients of calibration curves are not high in internal standard normalization method and predicted relative errors on the prepared samples are much high, so internal standard normalization method cannot be effectively used in the quantitative analysis of HCO3(-), SO4(2-) in the water. And with the multiple linear regression, the analysis accuracy was improved effectively. The calibration curve of PLS based on dominant factor showed that the SO4(2-) and HCO3(-) of pre-made solution with correlation coefficient R2 of 0.990 and 0.916 respectively. The 30 mmol . L(-1) of SO4(2-) and 20 mmol . L(-1) of HCO3(-) in two target samples were determined with the relative errors lower than 3.262% and 5.267% respectively. SO4(2-) in the coastal waters as the research object was analyzed by above-mentioned methods, comparing with 28.01 mmol . L(-1) by ion chromatography. It was demonstrated that PLS based on dominant factor method is superior to the rest of the three analysis methods, which can be used in situ calibration, with the mean relative error about 1.128%. All the results show that analysis accuracy would be improved by the PLS based on dominant factor method to predict concentration of acid radical ions. PMID- 26669166 TI - [Raman Spectra Study on Topochemistry in Miscanthus * giganteus Cell Walls During Dilute Acid Pretreatment]. AB - Confocal Raman microspectroscopy (CRM) represents a powerful technique that can provide insights into topochemistry in lignocellulosic biomass cell wall. In this work, CRM was used to explore the impact of dilute acid (DA) pretreatment on the topochemistry of lignin and hydroxycinnamic acid (HCA) in the-fiber cell walls of Miscanthus * giganteus internode. Raman spectra extracted from different morphological regions of untreated fiber cell walls indicated the heterogeneous concentration of lignin and HCA. There is a companied trend between them, that is, regions where there is the higher lignin concentration have the higher concentration of HCA. When treated with DA, it was found that the intensity of 1600 cm(-1) (lignin) and 1170 cm(-1) (HCA) were decreased, which could be contributed to the partially removal of lignin and HCA. The removal rate in different morphological areas followed the decreasing order: secondary cell wall (SW) > compound middle lamella (CML) > cell corner middle lamella (CCML). The increase of the Raman band intensity ratio (1170/1600) indicated the preferential removal of lignin in the SW and CML as a result of DA pretreatment, while the constant of the ratio meant there is no preference between lignin and HCA in the CCML. The research will provide the deep understanding of the topochemistry of lignin and HCA at sub-cellular level during DA pretreatment, meanwhile, it also expands the application of Raman spectra in the research area of plant cell wall. PMID- 26669167 TI - [Study on Mineralogical Characteristics of Quartz and Calcite from Feieling Skarn Type Pb-Zn Deposit in Southwest Margin of Yunkai Massif]. AB - The Feieling Pb-Zn deposit of skarn-type is located the in Southwest margin of Yunkai massif, China. This ore deposit can be divided into wall rock near ore, concealed rock mass, endoskarn, exoskarn and orebody. The Raman and FTIR spectrum are conducted to study the mineralogical characteristics of quartz and calcite from five types of rocks from Feieling skarn-type deposit. The analysis shows that the quartz included in the near ore wall rock, endoskarn and exoskarn, comparing with recrystallized quartz of concealed rock mass, has a tend to change into low symmetry quartz in varying degrees. The crystalinity and order degree of quartz from near ore wall rock to concealed rock mass and to endoskarn are becoming higher, but that of quartz from different exoskarn samples display no regular. The origin or the quartz microstructure changes may be related to the multi-stage evolution of skarn mineralization process. The quartz, included in near ore wall rock, endoskarn and exoskarn, become easier to recrystallize and adjust microstructure under the influence of the multi-stage hydrothermal and temperature effect. In anyone sample, the earlier crystalline calcite, showing subhedral-euhedral crystal, display higher crystalinity and order degree. On the contrary, the later crystalline calcite, showing xenomorphic crystal, display lower crystalinity and order degree. Calcite crystal of exoskarn rock contains some silica impurity, while endoskarn and orebody rock is pure. The purity of calcite crystal may relate to Multi-stage evolution of skarn mineralization process. At the early and late skarn stage, active silica-containing fluid is easier to join into calcite, which is under higher temperature environments. On the contrary, at the late quartz-surfide stage, the later crystalized calcite displays higher purity, which is under lower temperature environments. Therefore, spectral characteristics of quartz and calcite reflect multi-stage evolution of skarn mineralization process. PMID- 26669168 TI - [Research on Quantitative Analytical Model for Determination of Phosmet by Using Surface Enhanced Raman Spectroscopy]. AB - Raman spectroscopy combined with surface enhanced technology was adopted for analysis of phosmet pesticide. Continuous wavelet transforms (CWT) and successive projections algorithm (SPA) were used for Raman spectral preprocess and characteristic Raman shifts selection, respectively. Multi-linear regression (MLR) was used for spectral modeling. It is shown that enhanced chips can achieve enhanced Raman spectral signal for low concentration of pesticides. CWT can improve spectral resolution and smoothness, and remove translation error. Characteristic Raman shifts selection method of SPA can improve analytical precision, and simplify modeling variables of MLR. CWT-SPA-MLR model can improve correlation coefficient (r) of prediction from 0.823 to 0.903, and reduce root mean square error of prediction (RMSEP) from 1.640 to 1.122. CWT-SPA-MLR method can be used for constructing analytical models for Raman spectra and has good interpretability and repeatability. PMID- 26669169 TI - [Application of Raman Spectroscopy Technique to Agricultural Products Quality and Safety Determination]. AB - The quality and safety of agricultural products and people health are inseparable. Using the conventional chemical methods which have so many defects, such as sample pretreatment, complicated operation process and destroying the samples. Raman spectroscopy as a powerful tool of analysing and testing molecular structure, can implement samples quickly without damage, qualitative and quantitative detection analysis. With the continuous improvement and the scope of the application of Raman spectroscopy technology gradually widen, Raman spectroscopy technique plays an important role in agricultural products quality and safety determination, and has wide application prospects. There have been a lot of related research reports based on Raman spectroscopy detection on agricultural product quality safety at present. For the understanding of the principle of detection and the current development situation of Raman spectroscopy, as well as tracking the latest research progress both at home and abroad, the basic principles and the development of Raman spectroscopy as well as the detection device were introduced briefly. The latest research progress of quality and safety determination in fruits and vegetables, livestock and grain by Raman spectroscopy technique were reviewed deeply. Its technical problems for agricultural products quality and safety determination were pointed out. In addition, the text also briefly introduces some information of Raman spectrometer and the application for patent of the portable Raman spectrometer, prospects the future research and application. PMID- 26669170 TI - [Year Discrimination of Mild Aroma Chinese Liquors Using Three-Dimensional Fluorescence Spectroscopy Combined with Parallel Factor and Neural Network]. AB - Three-dimensional fluorescence spectroscopy coupled with parallel factor analysis and neural network was applied to the year discrimination of mild aroma Chinese liquors. The excitation-emission fluorescence matrices (EEMs) of 120 samples with various years were measured by FLS920 fluorescence spectrometer. The trilinear decomposition of the data array was performed and the loading scores of and the excitation-emission profiles of four components were also obtained. The scores were employed as the inputs of the BP neural networks and the PARAFAC-BP identification model was constructed. 10 samples were collected from 10, 20 and 30 years of liquors respectively, and 30 samples were selected as the test sets. The remaining 90 samples were used as the training sets to build the training model. The year prediction of unknown samples was also carried out, and the prediction accuracy was 90%, 100% and 100%, respectively. Meanwhile, the discrimination analysis method and the multi-way partial least squares discriminant analysis were compared, namely PARAFAC-BP and NPLS-DA. The results indicated that parallel factor combined with the neural network (PARAFAC-BP) has higher prediction accuracy. The proposed method can effectively extract the spectral characteristics, and also reduce the dimension of the input variables of neural network. A good year discrimination result was finally achieved. PMID- 26669171 TI - Study on the Non-Uniformity Calibration of Space-Born Differential Optical Absorption Spectrometer. AB - Space-borne differential optical absorption spectrometer is a nadir viewing wide field imaging spectrometer, which adopts two-dimensional CCD detector arrays. The pixel response non-uniformity exists in each column of spatial dimension, which will introduce high-frequency instrument-related spectral structures in the measurement data. However, the non-uniformity calibration of space-born imaging spectrometer is difficulty due to two factors: the spectral smile effect and the large field of view. For this reason, a method of non-uniformity calibration is discussed in detail. The result shows that the spectral smile effect and non uniformity of full FOV image are corrected effectively, and high-frequency instrument-related structures in the measurement data are removed. PMID- 26669172 TI - Study on the Relationship between the Depth of Spectral Absorption and the Content of the Mineral Composition of Biotite. AB - The mineral composition of rock is one of the main factors affecting the spectral reflectance characteristics, and it's an important reason for generating various rock characteristic spectra. This study choose the rock samples provided by Jet Propulsion Laboratory (JPL) (including all kinds of mineral percentage of rocks, and spectral reflectances range from 0.35 to 2.50 MUm wavelength measured by ASD spectrometer), and the various types of mineral spectral reflectances contained within the rocks are the essential data. Using the spectral linear mixture model of rocks and their minerals, firstly, a simulation study on the mixture of rock and mineral composition is achieved, the experimental results indicate that rock spectral curves using the model which based on the theory of the linear mixture are able to simulate better and preserve the absorption characteristics of various mineral components well. Then, 8 samples which contain biotite mineral are picked from the rock spectra of igneous, biotite contents and the absorption depth characteristics of spectral reflection at 2.332 MUm, furthermore, a variety of linear and nonlinear normal statistical models are used to fit the relationship between the depth of absorption spectra and the content of the mineral composition of biotite, finally, a new simulation model is build up with the Growth and the Exponential curve model, and a statistical response relationship between the spectral absorption depth and the rock mineral contents is simulated by using the new model, the fitting results show that the correlation coefficient reaches 0.9984 and the standard deviation is 0.572, although the standard deviation using Growth and Exponential model is less than the two model combined with the new model fitting the standard deviation, the correlation coefficient of the new model had significantly increased, which suggesting that the, new model fitting effect is closer to the measured values of samples, it proves that the simulation results of new model is closer to the measured value. PMID- 26669173 TI - [Review on Application of Optical Scattering Spectroscopy for Elastic Wave Velocity Study on Materials in Earth's Interior]. AB - In-situ experimental results on the elastic wave velocity of Earth materials at high pressure and high temperature in combination with data from seismic observation can help to inverse the chemical composition, state and migration of materials in Earth's interior, providing an important approach to explore information of deep earth. Applying the Brillouin scattering into the Diamond Anvil Cell (DAC) to obtain the in situ elastic wave velocities of minerals, is the important approach to investigate elastic properties of Earth's Interior. With the development of DAC technology, on the one hand, the high temperature and high pressure experimental environment to simulate different layers of the earth can be achieved; on the other hand, the optical properties of DAC made many kinds of optical analysis and test methods have been widely applied in this research field. In order to gain the elastic wave velocity under high temperature and high pressure, the accurate experimental pressure and heating temperature of the sample in the cavity should be measured and calibrated first, then the scattering signal needs to dealt with, using the Brillouin frequency shift to calculate the velocity in the sample. Combined with the lattice constants obtained from X ray technique, by a solid elastic theory, all the elastic parameters of minerals can be solved. In this paper, firstly, application of methods based on optical spectrum such as Brillouin and Raman scattering in elasticity study on materials in Earth's interior, and the basic principle and research progress of them in the velocity measurement, pressure and temperature calibration are described in detail. Secondly, principle and scope of application of two common methods of spectral pressure calibration (fluorescence and Raman spectral pressure standard) are analyzed, in addition with introduce of the application of two conventional means of temperature calibration (blackbody radiation and Raman temperature scale) in temperature determination. Lastly, geophysical applications of mineral elasticity are discussed on the basis of the recent research results derive from Brillouin scattering system of wave velocities for major minerals in Earth's lower mantle (perovskite, ferropericlase, etc.), and the future research work is inspected. PMID- 26669174 TI - [Estimation of Winter Wheat Biomass Using Visible Spectral and BP Based Artificial Neural Networks]. AB - The objective of this study was to evaluate the feasibility of using color digital image analysis and back propagation (BP) based artificial neural networks (ANN) method to estimate above ground biomass at the canopy level of winter wheat field. Digital color images of winter wheat canopies grown under six levels of nitrogen treatments were taken with a digital camera for four times during the elongation stage and at the same time wheat plants were sampled to measure above ground biomass. Canopy cover (CC) and 10 color indices were calculated from winter wheat canopy images by using image analysis program (developed in Microsoft Visual Basic). Correlation analysis was carried out to identify the relationship between CC, 10 color indices and winter wheat above ground biomass. Stepwise multiple linear regression and BP based ANN methods were used to establish the models to estimate winter wheat above ground biomass. The results showed that CC, and two color indices had a significant cor- relation with above ground biomass. CC revealed the highest correlation with winter wheat above ground biomass. Stepwise multiple linear regression model constituting CC and color indices of NDI and b, and BP based ANN model with four variables (CC, g, b and NDI) for input was constructed to estimate winter wheat above ground biomass. The validation results indicate that the model using BP based ANN method has a better performance with higher R2 (0.903) and lower RMSE (61.706) and RRMSE (18.876) in comparation with the stepwise regression model. PMID- 26669175 TI - Spectral Characteristics of Salinized Soils during Microbial Remediation Processes. AB - In this study, the spectral reflectance of saline soils, the associated soil salt content (SSC) and the concentrations of salt ions were measured and analysed by tracing the container microbial remediation experiments for saline soil (main salt is sodium chloride) of Dongying City, Shandong Province. The sensitive spectral reflectance bands of saline soils to SSC, Cl- and Na+ in the process of microbial remediation were analysed. The average-dimension reduction of these bands was conducted by using a combination of correlation coefficient and decision coefficient, and by gradually narrowing the sampling interval method. Results showed that the tendency and magnitude of the average spectral reflectance in all bands of saline soils during the total remediation processes were nearly consistent with SSC and with Cl- coocentration, respectively. The degree of salinity of the soil, including SSC and salt ion concentrations, had a significant positive correlation with the spectral reflectance of all bands, particularly in the near-infrared band. The optimal spectral bands of SSC were 1370 to 1445 nm and 1447 to 1608 nm, whereas the optimal spectral bands of Cl- and Na+ were 1336 to 1461 nm and 1471 to 1561 nm, respectively. The relationship model among SSC, soil salt ion concentrations (Cl- and Na+) and soil spectral reflectance of the corresponding optimal spectral band was established. The largest R2 of relationship model between SSC and the average reflectance of associated optimal band reached to 0.95, and RMSEC and RMSEP were 1.076 and 0.591, respectively. Significant statistical analysis of salt factors and soil reflectance for different microbial remediation processes indicated that the spectral response characteristics and sensitivity of SSC to soil reflectance, which implied the feasibility of high spectrum test on soil microbial remediation monitoring, also provided the basis for quick nondestructive monitoring soil bioremediation process by soil spectral reflectance. PMID- 26669176 TI - [Structure and Anti-Tumor Activity of Bovine alpha-Lactalbumin after Binding Linoleic Acid]. AB - The structure changes of alpha-lactalbumin after binding oleic acid and linoleic acid, including hydrophobic amino acids, hydrophobic regions, tertiary structure, secondary structure, was studied by intrinsic fluorescence, ANS-binding intrinsic fluorescence and circular dichroism spectrum, respectively. The anti-tumor activity of the lactalbumin-oleic acid complex and lactalbumin-linoleic acid complex was measured using the methylene blue method. It can be seen from the fluorescence spectra that a significant red-shift from 331.07 to 337.67 nm and 337.60 nm of alpha-lactalbumin occurred after binding of oleic acid and linoleic acid, respectively. Together with the ANS-binding spectra, which exhibited a blue shift (from 516.20 to 514.10 nm and 508.50 nm, respectively) with an increased fluorescence intensity, it can be indicated that binding of oleic acid and linoleic acid lead to the exposure of hydrophobic amino acids and hydrophobic regions. Results of circular dichroism spectra indicated the partial loss of the tertiary structure, and an decrease of beta-turn and random coil, which turn to the beta-sheet structure. Furthermore, the anti- tumor activity of the two complexes was verified on the three types of tumor cells. This study laid a theoretical basis for the development of anti-tumor drugs. PMID- 26669177 TI - [Biosorption and Biomineralization of Uranium(VI) from Aqueous Solutions by Landoltia Punctata]. AB - The biosorption and biomineralization characteristics of uranium by the duckweed Landoltia punctata was investigated in aqueous solutions enriched with 1 to 250 mg . L(-1) of U(VI) supplied as uranyl nitrate [UO2(NO3)2 . 6H2O]. The maximum uranium removal for the plant cultivar occurred at pH 4~5 of solution and their uranium removal efficiencies exceeded 90% after 24 h. In kinetics studies, the dried powder of duckweed can finished nearly 80% adsorption within 5 min, the batch adsorption equilibrium can be reached within 24 h for the living and dried powder of duckweed, Both for the living and dried powder of duckweed, the experimental data were well fitted by the pseudo-second-order rate model with the degree of fitting (r) higher than 0.99. The adsorption isotherms could be better described by the Freundlich model than the Langmuir model. In addition, Fourier transform infrared spectroscopy (FTIR) revealed that the surface of Landoltia punctata possess many active groups such as hydroxyl, carboxyl, phosphate and amide groups, the hydroxyl, amino groups involved in adsorption of U(VI) by living and dried powder of Landoltia punctata, and the phosphate groups also participated in the adsorption behavior of U(VI) by the living Landoltia punctata. The living Landoltia punctata reduction part of U(VI) to U(IV) was observed by XPS analysis. SEM and energy dispersive X-ray spectroscopy (EDS) of duckweed from 10~200 mg . L(-1) uranium treatments indeed showed root surface of living Landoltia punctata formed a significant portion of U precipitates with nanometer sized schistose structures that consisted primarily U and P, not containing C. Inorganic phosphate was released by the root cells of Landoltia punctata during the experiments providing ligands for formation of insoluble U(VI) and U(IV) phosphates. The distinct uranium peaks in the EDS spectra of the cluster on the root surface can be observed after biosorption and the uranium and phosphorus mass ratio of the cluster spot was measured to be 82.5% and 8.76% of the total component weight, respectively, and the atomic percentage of 30.89% and 25.19%, respectively. It is worth noting that the phosphorus mass ratio and the atomic rate of the control group is only 0.24% and 0.11%, respectively. But there was no similar crystals observed on the surface of dried powder of Landoltia punctata after biosorption. The present work suggests that living and dried powder of Landoltia punctata can remove more than 90% U(VI) from solution simultaneously precipitated together with phosphate by the living Landoltia punctata, and the dried powder of Landoltia punctata adsorption U(VI) is mainly through the effect of electrostatic attraction, ion exchange and complexation coordination, etc. Here, for the first time, the presence of U immobilization mechanisms within one aquatic plant is reported using Landoltia punctata. PMID- 26669178 TI - [Failure Prediction of Power-Shift Steering Transmission Based on Oil Spectral Analysis with Wiener Process]. AB - The most common methodology used in element concentration measurement and analyzing of wear particles is Atomic emission (AE) spectroscopy. As an indirect measuring method, the oil spectral data is introduced to indicate the performance degradation and the residual life prediction in the reliability evaluation of Power shift steering transmission (PSST). Stochastic methods especially the Wiener process is convenient in solving and analyzing the unitary degradation failure indicated by the oil spectral data. The oil data have been sampled in the real operating condition, and the data set has more than 50 samples taken from PSST. The mean values and time-dependent characteristics of three indicating elements are statistically obtained by the linear regression analysis. The model of the degradation and failure prediction has been proposed based on the Wiener process with the positive drift. For modeling and simulation the software R was used. Therefore, the trend curves of diffusion process with their First Hitting Time have been predicted. Through comparison, the time intervals of condition based maintenance have been extended as 27 Mh (15.9%). This will save the cost of maintenances by eliminate the preventive maintained cycles. The advantage and novelty of the outcomes presented in the article are that the stochastic process might be applied for predicting the degradation failure occurrence and also for optimizing the maintenance intervals and the cost-benefit. As might be expected, the method can be extended to other cases of wear prediction and evaluation in complex mechanical system. PMID- 26669179 TI - [The Hydrothermal Synthesis, Structure and Spectroscopy Study on (H2dap)6H[V12B16O54(OH)4] . 12H2O (dap = 1, 2-diaminopropane)]. AB - A polyoxovanadium borate (H2 dap)6H[V12B16O54(OH)4] . 12H2O (dap=1,2 diaminopropane) with novel structure was hydrothermally synthesized and characterized by the single crystal X-ray diffraction. It crystallizes in triclinic system with space group Piand unit cell parameters a=19.027(4), b=16.142(3) A, c=26.679(5) A, alpha=90 degrees , beta=101.06(3) degrees , gamma=90 degrees , V=8042(3) A3, Z=4, Dc=1.962 g . cm(-3), MU=1.456 mm(-1), F(000)=4776, the final R1=0.0626, wR2=0.1927, S=1.003,for 7635 observed reflections with I>2sigma(I). It is showed that the compound 1 is composed of V12B16 clusters unit and dap which is as a counter ion, and a two-dimensional layered structure is obtained by the effect of hydrogen bonding between the cluster units and dap, and between the layers via strong hydrogen bonds to form a three-dimensional supramolecular structure. The compound 1 were also characterized by IR, two-dimensional infrared (2D IR) correlation spectroscopy with magnetic and thermal perturbation, UV/Vis DRS spectra. The relationship between the structure and spectroscopy properties was discussed. The IR spectrum showed that the antisymmetric stretching vibration absorption peak nuas (V-OMU) and symmetric stretching vibration absorption peaks nus (V-OMU) appeared at 775 and 683 cm(-1) respectively, whereas the vibration absorption peak in nu(B-O) of BO3 and the vibration absorption peak in nu(B-O) of BO4 appeared at 1350 and 1050 cm(-1) respectively. The response of the stretching vibrations of B-O and V-O was detected in the 2D IR correlation spectra with magentic perturbation. In addition, the response of the stretching vibrations of B-OH, B-O and V-O-V was detected in the 2D IR correlation spectra with thermal perturbation. PMID- 26669180 TI - [Research on Modeling Method for Chlorophyll Content Fine Measurement Based on Neural Network]. AB - Aiming at SPAD values of living plant leaf chlorophyll content affected easily by the blade thickness, water content, etc, a fine retrieval method of chlorophyll content based on multiple parameters of neural network model is presented. The SPAD values and water index (WI) of leaves were obtained by the leaf transmittance under the irradiation of light central wavelength in 650 nm, 940 nm, 1450 nm respectively. Meanwhile, the corresponding blade thickness is got by micrometer and the chlorophyll content is measured by spectrophotometric method. To modeling samples, the single parameter model between SPAD values and chlorophyll content was built and the nonlinear model between WI, thickness, SPAD values and chlorophyll content was established based on BP neural network. The predicted value of chlorophyll content of test samples were calculated separately by two models, and the correlation and relative errors were analyzed between predicted values and actual values. 340 samples of three different plant leaves were tested by the method described above in experiment. The results showed that compared with single parameter model, the prediction accuracy of three different plant samples were improved in different degrees, the average absolute relative error of chlorophyll content of all pooled samples predicted by BP neural network model reduced from 7.55% to 5.22%. The fitting determination coefficient is increased from 0.83 to 0.93. The feasibility were verified in this paper that the prediction accuracy of living plant chlorophyll content can improved effectively using multiple parameter BP neural network model. PMID- 26669181 TI - [Study of Rapid Species Identification of Bacteria in Water]. AB - Multi-wavelength ultraviolet visible (UV-Vis) transmission spectra of bacteria combined the forward scattering and absorption properties of microbes, contains substantial information on size, shape, and the other chemical, physiological character of bacterial cells, has the bacterial species specificity, which can be applied to rapid species identification of bacterial microbes. Four different kinds of bacteria including Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Klebsiella pneumonia which were commonly existed in water were researched in this paper. Their multi-wavelength UV-Vis transmission spectra were measured and analyzed. The rapid identification method and model of bacteria were built which were based on support vector machine (SVM) and multi-wavelength UV Vis transmission spectra of the bacteria. Using the internal cross validation based on grid search method of the training set for obtaining the best penalty factor C and the kernel parameter g, which the model needed. Established the bacteria fast identification model according to the optimal parameters and one against-one classification method included in LibSVM. Using different experimental bacteria strains of transmission spectra as a test set of classification accuracy verification of the model, the analysis results showed that the bacterial rapid identification model built in this paper can identification the four kinds bacterial which chosen in this paper as the accuracy was 100%, and the model also can identified different subspecies of E. coli test set as the accuracy was 100%, proved the model had a good stability in identification bacterial species. In this paper, the research results of this study not only can provide a method for rapid identification and early warning of bacterial microbial in drinking water sources, but also can be used as the microbes identified in biomedical a simple, rapid and accurate means. PMID- 26669182 TI - [Identification of Pummelo Cultivars Based on Hyperspectral Imaging Technology]. AB - Existing methods for the identification of pummelo cultivars are usually time consuming and costly, and are therefore inconvenient to be used in cases that a rapid identification is needed. This research was aimed at identifying different pummelo cultivars by hyperspectral imaging technology which can achieve a rapid and highly sensitive measurement. A total of 240 leaf samples, 60 for each of the four cultivars were investigated. Samples were divided into two groups such as calibration set (48 samples of each cultivar) and validation set (12 samples of each cultivar) by a Kennard-Stone-based algorithm. Hyperspectral images of both adaxial and abaxial surfaces of each leaf were obtained, and were segmented into a region of interest (ROI) using a simple threshold. Spectra of leaf samples were extracted from ROI. To remove the absolute noises of the spectra, only the date of spectral range 400~1000 nm was used for analysis. Multiplicative scatter correction (MSC) and standard normal variable (SNV) were utilized for data preprocessing. Principal component analysis (PCA) was used to extract the best principal components, and successive projections algorithm (SPA) was used to extract the effective wavelengths. Least squares support vector machine (LS-SVM) was used to obtain the discrimination model of the four different pummelo cultivars. To find out the optimal values of sigma2 and gamma which were important parameters in LS-SVM modeling, Grid-search technique and Cross Validation were applied. The first 10 and 11 principal components were extracted by PCA for the hyperspectral data of adaxial surface and abaxial surface, respectively. There were 31 and 21 effective wavelengths selected by SPA based on the hyperspectral data of adaxial surface and abaxial surface, respectively. The best principal components and the effective wavelengths were used as inputs of LS SVM models, and then the PCA-LS-SVM model and the SPA-LS-SVM model were built. The results showed that 99.46% and 98.44% of identification accuracy was achieved in the calibration set for the PCA-LS-SVM model and the SPA-LS-SVM model, respectively, and a 95.83% of identification accuracy was achieved in the validation set for both the PCA-LS-SVM and the SPA- LS-SVM models, which were built based on the hyperspectral data of adaxial surface. Comparatively, the results of the PCA-LS-SVM and the SPA-LS-SVM models built based on the hyperspectral data of abaxial surface both achieved identification accuracies of 100% for both calibration set and validation set. The overall results demonstrated that use of hyperspectral data of adaxial and abaxial leaf surfaces coupled with the use of PCA-LS-SVM and the SPA-LS-SVM could achieve an accurate identification of pummelo cultivars. It was feasible to use hyperspectral imaging technology to identify different pummelo cultivars, and hyperspectral imaging technology provided an alternate way of rapid identification of pummelo cultivars. Moreover, the results in this paper demonstrated that the data from the abaxial surface of leaf was more sensitive in identifying pummelo cultivars. This study provided a new method for to the fast discrimination of pummelo cultivars. PMID- 26669183 TI - [Estimation of Fraction of Absorbed Photosynthetically Active Radiation for Winter Wheat Based on Hyperspectral Characteristic Parameters]. AB - Estimating fraction of absorbed photosynthetically active radiation (FPAR) precisely has great importance for detecting vegetation water content, energy and carbon cycle balance. Based on this, ASD FieldSpec 3 and SunScan canopy analyzer were applied to measure the canopy spectral reflectance and photosynthetically active radiation over whole growth stage of winter wheat. Canopy reflectance spectral data was used to build up 24 hyperspectral characteristic parameters and the correlation between FPAR and different spectral characteristic parameters were analyzed to establish the estimation model of FPAR for winter wheat. The results indicated that there were extremely significant correlations (p<0.01) between FPAR and hyperspectral characteristic parameters except the slope of blue edge (Db). The correlation coefficient between FPAR and the ratio of red edge area to blue edge area (VI4) was the highest, reaching at 0.836. Seven spectral parameters with higher correlation coefficient were selected to establish optimal linear and nonlinear estimation models of FPAR, and the best estimating models of FPAR were obtained by accuracy analysis. For the linear model, the inversin model between green edge and FPAR was the best, with R2, RMSE and RRMSE of predicted model reaching 0.679, 0.111 and 20.82% respectively. For the nonlinear model, the inversion model between VI2 (normalized ratio of green peak to red valley of reflectivity) and FPAR was the best, with R2, RMSE and RRMSE of predicted model reaching 0.724, 0.088 and 21.84% for. In order to further improve the precision of the model, the multiple linear regression and BP neural network methods were used to establish models with multiple high spectral parameters BP neural network model (R2=0.906, RMSE=0.08, RRMSE=16.57%) could significantly improve the inversion precision compared with the single variable model. The results show that using hyperspectral characteristic parameters to estimate FPAR of winter wheat is feasible. It provides a new method and theoretical basis for monitoring the dynamic change of FPAR in real time, effectively and accurately during the growth stage of winter wheat. PMID- 26669184 TI - [A Method to Estimate Metal Abundance from Stellar Spectra Using Ca Line Index]. AB - This paper presents a method to estimate stellar metallicity based on BP neural network and Ca line index. This method trains a BP ANN model from SDSS/SEGUE stellar spectra and parameters provided by SSPP. The values of Teff and the line index of Ca lines are the input of network while the [Fe/H] values are the oputput of the network. A set of samples are resampled from the set of all and then a network model is trained. The network can be used to predict the stellar metallicity from low-resolution spsectra. The experiment shows that the proposed method can accurately and effectively measure the [Fe/H] from the stellar spectra. PMID- 26669185 TI - [Hadamard Transform NIR Spectrometer for the Biological Processes]. AB - Monitoring the consumption of nutrients of biological process helps control the growth environment of the microbes. It ensures the microbes are always in the best growing conditions, so as to maximize the yield of the target product. To monitor the content of glycerol, methanol and glucose in yeast culture medium, a new NIR spectrometer was developed which is based on Hadamard Transform (HT)technique. It uses the Near IR probe, which was designed all by ourselves, to collect the spectral signals, and uses the Digital Micro-mirror Devices(DMD) to complete the coding and modulation of Hadamard template. With self-developed software, aiming at spectral acquisition and spectral processing, the spectrometer has realized the real-time monitoring. The designs of optical path, Near IR probe, hardware circuit and software modules are given. Through lots of experiments, it turns out that the value of stray light is 0.875% and the volatility is +/-4.28% in this spectrometer. The spectrometer shows high precision in a series of tests which means it totally meets the requirements of monitoring the biological processes. PMID- 26669186 TI - [A Surface Plasmon Micro-Ring Sensor Suitable for Humidity Sensing]. AB - Temperature is a very important parameter in scientific research, production and life. Almost all the properties of materials are related to temperature. The precise measurement of the temperature is a very important task, so the temperature sensor is widely used as a core part in the temperature measuring instrument. A novel surface plasmon micro-ring sensor suitable for humidity sensing is presented in this paper. The sensor uses a multi-layered surface plasmon waveguide structure and choosing Polyimide (Polyimide, PI) as the moisture material. We get the transfer function of surface plasmon micro-ring sensor by using transfer matrix method. Refractive indexes of Polyimide and the multilayer waveguide structure change as environment relative humidity changes, thus leading to an obvious peak drift of output spectrum. The paper mainly discusses the influence of the changes of the refractive index of humidity sensing parts on the output spectrum, and the transmission characteristics of multilayer waveguide structure. Through the finite element method and the theoretical simulation of Matlab, We can draw: When the length between the two coupling points of the U-shaped waveguide is an integer multiple of circumference of the micro-ring, an obvious drift in the horizontal direction appears, the free spectral range (FSR) doubled and the sensitivity is 0.0005 MUm/%RH; When the external environment relative humidity RH changes from 10% to 100% RH, scatter is change between including (including 0.005 m to 0.005 m, compared to other humidity sensor, the Sensitivity of sensor improves 10~50 times and the transmission is very stable. Results show that the design of surface plasma micro ring sensors has better sensitivity, stable performance and can be used in the humidity measurement, achieving a high sensitivity in the sense of humidity when the wide range of filter frequency selection is taken into account, and providing a theoretical basis for the preparation of micro-optics. PMID- 26669187 TI - [VMTBB-Based Spectral Radiometric Calibration of NIR Fiber Coupled Spectrometer]. AB - The medium temperature black body (MTBB) is conventional high precision equipment used as spectral radiometric scale in infrared spectral region. However, in near infrared (NIR) spectral region, there are few papers about spectral radiometric calibration by using MTBB, that is because NIR spectral region is the borderland of its effective spectral region. The main research of this paper is spectral radiometric calibration method by using MTBB in NIR spectral region. Accordingly, this paper is devoted mostly to a discussion of how the calibration precision could be affected by selecting different structural parameters of calibration model. The purpose of this paper is to present the results of research and provide technical reference for improving the traceability in NIR spectral radiometric calibration. In this paper, a NIR fiber coupled spectrometer, whose wavelength range covers from 950 to 1700 nm, has been calibrated by a MTBB with adjustable temperature range from 50 to 1050 degrees C. Concentrating on calibration process, two key points have been discussed. For one thing, the geometric factors of radiation transfer model of the calibration systems have been compared between traditional structure and fiber direct-coupled structure. Because the fiber direct-coupled model is simple and effective, it has been selected instead of traditional model based on the radiation transfer between two coaxial discs. So, it is an advantaged radiation transfer model for radiometric calibration of fiber coupled spectrometer. For another thing, the relation between calibration accuracy and structural parameters of calibration model has been analyzed intensively. The root cause is scale feature of attribute of calibration data itself, which is the nonlinear structure in scales of spectral data. So, the high precision calibration needs nonlinear calibration model, and the uniform sampling for scale feature is also very important. Selecting sample is an inevitable problem when the nonlinear model is explained by small sample dataset. As the analytic results, there are obviously influences for the calibration precision among different strategies of selecting model's structural parameters. The calibration precision, which is mathematical described by standard deviation of spectral data for calibration, could be from +/-0.1% to +/ 1%. PMID- 26669188 TI - [Effects of Electroacupunctrue Combined with Dietary Control on Peroxisome Proliferator-activa- ted Receptor-alpha, and Liver Fatty Acid-binding Protein Levels in Non-alcoholic Fatty Liver Disease Rats]. AB - OBJECTIVE: To observe the effect of electroacupunctrue (EA) intervention or EA combined with dietary control on peroxisome proliferator-activated receptor (PPAR)-alpha, and liver fatty acid-binding protein (L-FABP) levels in non alcoholic fatty liver disease (NAFLD) rats, so as to reveal its mechanism underlying improvement of NAFLD. METHODS: Sixty SD male rats were randomly divided into common diet (control) group (n = 10) and high-fat diet group (n = 45). The NAFLD model was established by feeding the animals with high-fat forage (HFF, including cholesterol, sodium cholate, propylthiouracil, sucrose, lard and common forage) for 5 weeks. Forty NAFLD rats were then randomized into model, EA + HFF, low-fat forage (LFF) and EA+ LFF groups (n = 10 rats in each group). EA (4 Hz/20 Hz, 3 mA) was applied to ipsilateral "Zusanli" (ST 36),"Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 20 min, once daily for 4 weeks. The pathologic changes of the hepatic tissue were detected by H. E. staining. Serum total cholesterol (TC) and triglyceride (TG) contents were determined by using enzymatic methods, serum free fat acids (FFA) content was detected by colorimetry. The expression levels of PPAR-alpha and L-FABP protein and gene of the liver tissue were determined by Western blot and RT-PCR, respectively. RESULTS: H. E. staining showed that the hepatocytes presented moderate or severe bullous adipose degeneration in rats of the model group, vesicular steatosis in the EA + HFF and LFF groups, turned to almost normal but with small amount of lipid droplets in the EA + LFF group. The contents of serum TC, TG and FFA were significantly higher in the model group than in the control group (P < 0.05), and were obviously decreased in the EA + HFF, LFF and EA + LFF groups in comparison with the model group (P < 0.05). Compared to the control group, hepatic PPAR-alpha protein and mRNA were markedly down-regulated in the model group, and hepatic L FABP protein and mRNA considerably up-regulated in the model group (P < 0.05). Following EA intervention and low fat diet feeding, PPAR-alpha protein and mRNA were markedly up-regulated while L-FABP protein and mRNA remarkably down regulated in the EA + HFF, LFF and EA + LFF groups (P < 0.05). CONCLUSION: EA intervention or EA combined with dietary control can relieve hepatic pathological changes in NAFLD rats, which may be related to its effects in down-regulating blood lipid level and hepatic L-FABP protein and mRNA expression and in up regulating PPAR-alpha protein and mRNA expression, and the effect of combined treatment was relatively better than simple EA or LFF treatment. PMID- 26669189 TI - [Effect of Acupotomy Lysis at Cervical Acupoints on Expression of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinase 1 and Changes of Pulpiform Nucleus Ultrastructure in Rats with Degenerated Cervical Intervertebral Discs]. AB - OBJECTIVE: To observe the effect of acupotomy lysis at acupoints around the neck on expression of matrix metalloproteinase 1 (MMP-1), MMP-2 and tissue inhibitor of metalloproteinase 1 (TIMP-1) genes and ultrastructure of pulpiform nucleus in cervical intervertebral disc degeneration (IVDD) rats, so as to explore its mechanism underlying easing IVDD. METHODS: SD rats were randomly allocated to control (n = 15), model (n = 14), Jiaji (EX-B 2, n = 13), cervico-acupoint (n = 14) and medication groups (n = 14). The cervical IVDD model was established by using static-dynamic imbalance method. For rats of the Jiaji (EX-B 2) and cervico acupoint groups, EX-B 2-points of the cervical 2-7 segments, and peri-cervical acupoints: bilateral "Naokong" (GB 19) , "Naohu" (GV 17), "Dazhui" (GV 14), bilateral "Quyuan" (SI 13) and bilateral "Tianzong" (SI 11) were separately punctured with a needle-knife, once every 5 days for 3 times, and for rats of the medication group, Brufen Capsules (15 mg . kg(-1) . d(-1)) and Jingfukang Granule (0.5 mg . kg(-1) . d(-1)) were given by intragastric administration, once daily for 10 days. The expression levels of MMP-1, MMP-3 and TIMP-1 genes in the pulpiform nucleus of cervical intervertebral discs were detected by RT-PCR and changes of the ultrastructure of the pulpiform nucleus observed under transmission electron microscope. RESULTS: Compared to the control group, the expression levels of MMP-1 mRNA and MMP-3 mRNA of the cervical intervertebral disc tissues were significantly up-regulated in the model group (P < 0.05), and that of TIMP-1 mRNA was obviously down-regulated in the model group (P < 0.05). After the treatment, the increased expression of MMP-1 mRNA and MMP-3 mRNA and the decreased expression of TIMP-1 mRNA were reversed by acupotomy lysis and medication (P < 0.05) except TIMP-1 mRNA in the medication group (P > 0.05). No significant differences were found between the Jiaji (EX-B 2) and cervico acupoint groups in down-regulating MMP-1 mRNA and MMP-3 mRNA expression and up regulating TIMP-1 mRNA expression (P > 0.05). Results of electron microscope examinations showed that the ultrastructural injury changes of cells of the pulpiform nucleus were relatively milder in the Jiaji (EX-B 2) and cervico acupoint groups, followed by the medication group in comparison with those of the model group. CONCLUSION: Acupotomy lysis at acupoints around the neck can improve the ultrastructural changes of cells of the pulpiform nucleus of cervical intervertebral discs in IVDD rats, which is possibly by regulating the expression of MMP-1, MMP-3 and TIMP-1 genes. PMID- 26669190 TI - [Effect of Electroacupuncture Intervention on CaMK II-CREB Pathway in Spinal Cord in Rats with Spared Nerve Injury]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Weizhong" (BL 40)-"Huantiao" (GB 30) on expression of phosphorylated calcium/calmodulin dependent protein kinase II (p-CaMK II) and cAMP response element binding protein (p-CREB) in the spinal cord in rats with spared nerve injury (SNI), so as to explore its mechanism underlying easing neuropathic pain. METHODS: Sixty SD rats were randomly divided into five groups: control (sham operation) , model, EA, AP-5 (a NMDA receptor antagonist) and L-NAME (a non selective nitric oxide synthase, NOS inhibitor) (n = 12 in each group). The neuropathic pain model was established by sectioning the right tibal nerve and common peroneal nerve. EA intervention (2 Hz, 1 mA, increasing 1 mA/10 min) was applied to "Weizhong" (BL 40) and "Huantiao" (GB 30) on the injured side for 30 min, once a day for 7 days. Rats of the AP-5 and L-NAME groups were treated by intragastric administration of AP-5 (0.7 mg . kg(-1) . d(-1)) and L-NAME (60 mg . kg(-1) . d(-1)) respectively from the 11 th day after operation, once daily for 7 days. The mechanical pain thresholds were measured before the SNI procedure (baseline) and at the 10th and 16th day after the procedure. The expression of p CaMK II protein and p-CREB protein and gene of the spinal cord (L4-L6 segments) was determined by Western blot and fluorescence quantitative-polymerase chain reaction (PCR), separately. RESULTS: In comparison to the control group, the mechanical pain threshold was significantly decreased in the model group (P < 0.01). After EA intervention, the mechanical pain thresholds of the EA, AP-5 and L-NAME groups were obviously increased (P < 0.01, P < 0.05) on day 16 post SNI procedure. The expression levels of p-CaMK II and p-CREB proteins and CREB mRNA in the spinal cord were significantly higher in the model group than in the control group (P < 0.05). Compared with the model group, the expression levels of spinal p-CaMK II and p-CREB proteins and CREB mRNA were obviously down-regulated in the EA group (P < 0.05), but not in the AP-5 group and the L-NAME group (P > 0.055. CONCLUSION: EA intervention of BL 40-GB 30 may alleviate pain in neuropathic pain rats, which may be related to its effects in down-regulating spinal CaMK II-CREB pathway function. PMID- 26669191 TI - [Effect of Electroacupuncture Intervention on Expression of Cx 43 and Concentration of Glutamate in the Striatum of Rats with Parkinson's Disease]. AB - OBJECTIVE: To observe the action of electroacupuncture (EA) intervention on the expression of gap junction protein connexin 43 (Cx 43) and content of glutamate (Glu) in the striatum in Parkinson's disease (PD) rats, so as to reveal its mechanism underlying improvement of PD. METHODS: Forty male SD rats were randomly divided into normal control, sham operation, model and EA groups (n = 10 in each group). The PD model was duplicated by microinjection of 6-hydroxyldopamine (6 OHDA, 15 ug/rat) into the right striatum of rats (AP: 1.0, 1.0; R: 3.0, 4.5; H: 4.5, 6.0), and for control, the same dose of normal saline was injected into the right striatum for rats in the sham operation group. EA (2 Hz, 1 mA) was applied to "Fengfu" (GV 16) "Taichong" (LR 3) for 30 min, once a day for 2 weeks. The PD rats' rotational behavior changes (the numbers of rotations in 30 min) were detected following subcutaneous injection of apomorphine (0.5 mg/kg). The Glu concentration and the expression of Cx 43 in the striatum were detected by using high performance liquid chromatography (HPLC) and Western blot, respectively. RESULTS: No significant differences were found between the model group and EA group in the number of rotations before the treatment, between the control and sham operation groups in the levels of Glu content and Cx 43 protein expression in the striatum (P > 0.05). Compared with the control group, the Glu content and Cx 43 protein expression level were significantly increased in the model group (P < 0.01), while in comparison with the model group, the number of rotations was significantly reduced in the EA group (P < 0.05). Following EA intervention, both Glu content and Cx 43 expression were considerably down-regulated in the EA group compared with the model group (P < 0.05, P < 0.01). CONCLUSION: EA can improve PD rats' rotation behavior, which may be associated with its effects in down regulating the level of Glu and Cx 43 protein expression in the striatum. PMID- 26669192 TI - [Effect of Acupuncture Intervention on Expression of NF-kappaB Signal Pathway in the Hippocampus of Chronic Stress-induced Depression Rats]. AB - OBJECTIVE: To observe the influence of acupuncture intervention on the expression of pivotal pro-inflammatory molecules nuclear factor-kappaB (NF-kappaB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) of NF-kappaB inflammatory signal pathway in the hippocampus of depression rats, so as to explore its mechanism underlying improvement of depression. METHODS: Thirty-six male Sprague Dawley rats were randomly divided into four groups: control, model, acupuncture, and medication (fluoxetine, Flu) (n = 9 rats in each group). The depression model was established by using chronic unpredictable stress stimuli combined with solitary feeding for 28 days. Acupuncture treatment was applied to "Baihui" (GV 20) and "Neiguan" (PC 6) once every other day for 28 days. Fluoxetine was given to rats of the medication group (10 mg/kg) by gavage (p. o.) everyday for 28 days before the stress stimulation. The expression of NF-kappaB protein in the hippocampus tissue was detected by Western blot, and the contents of COX-2 and PGE2 were detected by ELISA. RESULTS: Compared to the control group, the levels of NF-kappaB protein expression, COX-2 and PGE2 contents in the hippocampus were significantly increased in the model group (P < 0.01). Compared to the model group, the levels of NF-kappaB protein expression, COX-2 and PGE2 contents in the hippocampus were significantly down-regulated in both the acupuncture and medication groups (P < 0.05; P < 0.01). There was no significant differences between the acupuncture and medication groups in the NF-kappaB protein expression, and COX-2 and PGE2 contents (P > 0.05). CONCLUSION: Acupuncture intervention can effectively reduce hippocampal NF-kappaB expression, and COX-2 and PGE2 levels in depression rats, which may contribute to its anti-depressant effect by inhibiting pro-inflammatory pathway to protect the neurons of hippocampus. PMID- 26669193 TI - [Effect of Electroacupuncture Stimulation of Different Tissues at "Huantiao" (GB 30) Acupoint on Expression of Phosphorylated JNK and c-jun in Spinal Cord of Rats with Sciatic Nerve Injury]. AB - OBJECTIVE: To observe the effects of electroacupuncture (EA) stimulation of different tissues (nerve stem, muscular layer) at "Huantiao" (GB 30) acupoint on expression of hosphorylated c-jun N-terminal kinase (p-JNK) and c-jun (p-c-jun) proteins in the lumbar spinal cord in rats with sciatic nerve injury, so as to explore its mechanism underlying improvement of peripheral neuropathic damage. METHODS: Forty-eight SD rats were randomly divided into normal, model (the left sciatic nerve severed), GB 30 deep needling (the acupuncture needle tip was inserted to the sciatic nerve trunk to elicit an instantaneous jerk of the hind limb) and GB 30 shallow needling (the needle tip was inserted to the muscle layer to evoke a local muscular contraction) groups (n = 12 rats in each group). EA stimuli were delivered at 2 Hz/100 Hz, 1 mA, 20 min in duration per treatment for 10 consecutive days. Histopathological changes were observed by Hematoxylin-eosin (HE) staining and immunohistochemical assay was carried out to examine the pathological change of spinal segments (L4-L5) and the expression of p-JNK and p c-jun proteins, respectively. RESULTS: For rats with the sciatic nerve severed, the spinal neurons became swelling, degeneration or even apoptosis. Acupuncture intervention reduced the number of apoptosic neurons and improved the pathological change, which was relatively better in the.deep needling group than in the shallow needling group. Likewise, the elevated spinal p-JNK and p-c-jun expression levels of the model group were significantly reduced by EA intervention (deep needling vs shallow needling, P < 0.01. CONCLUSION: Acupuncture can improve the spinal pathological changes in rats with sciatic nerve injury, which is probably achieved by decreasing the p-JNK and p-c-jun expression and inhibiting the JNK signaling pathway, and thereby, reducing the apoptosis of the spinal neurons. Deep needling results in greater benefits than shallow needling. PMID- 26669194 TI - [Effects of Electroacupuncture Stimulation of "Neiguan" (PC 6) at Different Frequencies on Plasma Vasoactive Substance Levels in Myocardial Ischemic Reperfusion Rats]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6) at different frequencies on plasma vasoactive substance levels in myocardial ischemia-reperfusion (MIR) injury rats, so as to explore its mechanisms underlying improvement of acute myocardial ischemia. METHODS: A total of 40 Wistar rats were randomized into control, model, high frequency (HF, 120 Hz) and low frequency (LF, 20 Hz) groups (n = 10 in each group). The MIR model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 40 min. EA (3 V, 120 Hz or 20 Hz) was applied to bilateral "Neiguan" (PC 6) for 50 min immediately after occlusion of ADB. Subsequently, the contents of plasma endothelin (ET), atrial natriuretic peptide (ANP), thromboxane B 2 (TXB2) and 6-Keto-PGF1, were assayed by radioimmunoassay, and the content of serum nitric oxide (NO) was detected by nitrate reductase method. RESULTS: Compared with the control group, the contents of plasma ET, ANP and TXB2 in the model group were significantly increased (P < 0.05), and that of plasma 6-Keto-PGF1alpha in the model group was notably decreased (P < 0.05), but no significant change was found in serum NO level (P > 0.05). Compared with the model group, the contents of plasma ET, ANP and TXB2 were considerably decreased, and plasma 6-Keto-PGF1alpha and serum NO contents were obviously increased in both HF and LF groups (P < 0.05). No significant differences were found between the HF and LF groups in plasma ET , ANP, TXB2 and 6-Keto-PGF1alpha contents (P > 0.05), but the HF EA was markedly superior to the LF EA in up-regulating the content of serum NO (P < 0.05). CONCLUSION: EA stimulation of "Neiguan" (PC 6) can down-regulate the contents of plasma ET, ANP and TXB2 and up-regulate contents of plasma 6-Keto-PGF1alpha and serum NO in MIR rats, which may contribute to its effect in relieving acute ischemic myocardial injury. The effect of HF EA is better than LF EA in raising blood NO level. PMID- 26669195 TI - [Effect of Electroacupuncture Intervention at Different Time-points on Levels of HSP 70, MDA, SOD and GSH-PX of Liver in Rats with Simulated Weightlessness]. AB - OBJECTIVE: To observe the effect of acupuncture intervention at different time points on the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH PX), the content of malonaldehyde (MDA) and expression of heat shock protein 70 (HSP 70) of liver tissue in rats with simulated weightlessness, so as to explore its mechanism underlying improvement of liver injury in rats with simulated weightlessness. METHODS: Twenty male Wistar rats were randomly divided into control group, model group, pre-acupuncture group and EA group, 5 rats in each. The model of simulated weightlessness was established by tail suspension for 4 week. One week before the tail suspension, the rats in the pre-acupuncture group were treated with electroacupuncture (EA) at "Shenshu" (BL 23), "Pishu"(BL 20) and "Sanyinjiao" (SP 6) for 30 min before treatment, once a day for 7 days. The rats in the EA group received tail suspension and acupuncture intervention at the same time. EA was applied for 30 min per treatment, once every other day for 14 times. Immunohistochemical staining was used to assay the expression of HSP 70 in the liver tissue. The activities of SOD and GSH-PX and content of MDA in liver tissues were examined by means of colourimetric method. Results Compared with the control group,the expression of HSP 70 and the content of MDA in the liver tissue were increased significantly (P < 0.01), and the activity of SOD and GSH-PX was notably reduced (P < 0.05) in the model group. Compared with the model group, the content of HSP 70 was significantly reduced in the pre-acupuncture group (P < 0.01). There were no significant changes in the levels of SOD, GSH-PX, MDA and HSP 70 in the EA group (P > 0.05). In comparison with the pre-acupuncture group, the activity of GSH-PX was lower (P < 0.05) and the content of MDA was higher (P < 0.05) in the EA group. CONCLUSION: EA-pretreatment can suppress the increase of liver HSP 70 immunoactivity in rats with simulated weightlessness, being likely to improve the antioxidant ability of liver. PMID- 26669196 TI - [Effects of Suspending Moxibustion at "Dazhui" (GV 14) on Neurogenic Inflammation in Asthma Rats]. AB - OBJECTIVE: To observe the effect of suspending-moxibustion stimulation of "Dazhui" (GV 14) with different quantities on the levels of nerve growth factor(NGF) , substance P(SP) , calcitonin gene-related peptide (CGRP), neurokinin A (NKA) , neurokinin B (NKB) and phosphorylated extracellular signal regulated kinases (pERK) in the bronchoalveolar lavage fluid (BALF) of asthma rats, so as to analyze its mechanisms underlying improving asthma. METHODS: Sixty male SD rats were randomly divided into six groups: blank control, model, 15 min moxibustion (15 min-moxi), 30 min-moxi, 60 min-moxi and 90 min-moxi (n = 10 rats in each group). The asthma model was established by intraperitoneal injection of suspension of egg protein, magaldrate, and inactivated Bacillus pertussis (on day 1 and 8), and inhaling the atomized ovalbumin saline (from day 15 on for 14 days). Mild moxibustion was conducted at "Dazhui" (GV 14) for 15 min, 30 min, 60 min and 90 min, respectively, once daily for 7 days. The levels of NGF, SP, CGRP, NKA, NKB, and pERK in the BALF were detected by ELISA (enzyme-linked immuno sorbent assay). RESULTS: The contents of NGF, SP, CGRP, NKA, NKB and pERK in the BALF in the model group were obviously higher than those in the blank control group (P < 0.01), suggesting an apparent inflammatory reaction in rats after modeling. Following moxibustion, the levels of NGF, SP, CGRP, NKA, NKB and pERK of the four treatment groups were significantly down-regulated compared with the model group (P < 0.01). The effect of 30 min-moxi group was obviously superior to that of 15 min-moxi group (P < 0.01), and those of 60 min-moxi and 90 min-moxi groups were markedly superior to those of 15 min-moxi and 30 min-moxi groups (P < 0.01) in down-regulating NGF, SP, CGRP, NKA, NKB, and pERK levels in the BALF. No significant differences were found between the 60 min-moxi and 90 min-moxi groups in down-regulating NGF, SP, CGRP, NKA, NKB, and pERK levels (P > 0.05). CONCLUSION: Suspending-moxibustion stimulation of GV 14 can down-regulate the contents of NGF, SP, CGRP, NKA, NKB, and pERK levels in the BALF in asthma rats, suggesting a relief of neurogenic inflammation reaction after moxibustion. The effect of moxibustion presents a time-dependant manner and peaks at 60 min. PMID- 26669197 TI - [Effect of Preconditioning of Catgut Implantation at Acupoints on Changes of Behavior and EEG in Epileptic Rats]. AB - OBJECTIVE: To observe the effect of preconditioning of catgut implantation on changes of behavior and EEG of rats with epilepsy. METHODS: Forty male Wistar rats were randomly divided into control, model, catgut implantation, medication groups (10 rats/group). The catgut implantation was performed at "Yintang" (EX 2) to "Baihui" (GV 20) and "Changqiang" (GV 1) on day 1, 4 and 7. The epileptic model was made by intraperitoneal injection of penicillin sodium on the last day of the treatment. In the medication group, intragastric administration of valproic acid sodium was conducted once a day for consecutive 7 days. Behavior measurement and EEG recording were carried out shortly after the penicillin administration. RESULTS: Compared with the model group, the seizure latency was notably increased in the catgut implantation group and the medication group (P < 0.01), without significant difference between the last two groups (P > 0.05). The degree of the seizure attack was less severe in the catgut implantation group and the medication group (P < 0.01), without significant difference between the two groups (P > 0.05). Similar to valproic acid sodium, catgut implantation significantly reduced the amplitude and accelerated the frequency of EEG (P < 0.01). CONCLUSION: Catgut implantation can delay the seizure attack latency, alleviate the severity, regulate the amplitude and frequency of the epileptiform discharges, giving rise to evident antiepileptic effect. PMID- 26669198 TI - [Effect of Acupuncture and Moxibustion Intervention on Contents of Serum Interleukin-7 and In- terleukin-18 in Cyclophosphamide-induced Immune Suppression in Tumor-bearing Mice]. AB - OBJECTIVE: To observe the effect of acupuncture and moxibustion intervention on the contents of serum IL-7 and IL-18 and white blood cell counts in cyclophosphamide (CTX)-induced hypofunction of immunity in tumor-bearing mice, so as to explore its mechanism underlying improvement of immune suppression caused by chemotherapy. METHODS: Sixty-four male Kunming mice were implanted with S 180 sarcoma at the left armpit (for making tumor-bearing model) , and then, randomized into control group, model group, acupuncture group and moxibustion group( 16 mice in each group). The mice of the latter 3 groups were injected with CTX (i. p. , 150 mg . kg(-1) . d(-1)), and those of the control group were injected (i. p.) with normal saline. Filiform acupuncture needle or moxibustion was applied to "Dazhui" (GV 14) , unilateral "Geshu" (BL 17) , "Shenshu"(BL 23) and "Zusanli"(ST 36) once daily for 3 or 5 days. Contents of serum IL-7 and IL-18 were detected by ELISA. RESULTS: In comparison with the control group, the plasma leukocyte counts from day 2 to day 5, the spleen index and serum IL-18 contents on day 3 and 5 after administration of CTX were significantly decreased, and serum IL-7 contents on day 3 and 5 after CTX remarkably increased in the model group (P < 0.05). Following the treatment, the spleen index on day 3 and serum IL 18 content on day 5 in the moxibustion group, serum IL-7 and IL-18 contents on day 3 and 5 in the acupuncture group were significantly up-regulated (P < 0.05). The effect of acupuncture was markedly superior to that of moxibustion in up regulating serum IL-18 contents on day 3 and 5 after the treatment (P < 0.05). No significant differences were found between the acupuncture and moxibustion groups in the leukocyte counts and spleen index after the treatment, and in serum IL-7 contents on day 3 (P > 0.05). CONCLUSION: Acupuncture and moxibustion can up regulate the serum IL-7 and IL-18 and white blood cell levels in immuno suppression mice, wnicn may contribute to their effects in relieving immune hypofunction caused by alkylating agent CTX. PMID- 26669199 TI - [Effect of Electroacupuncture Stimulation of Acupoints at the Distal Limbs on Heart Function of Volunteers with Acute Hypoxia]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of different acupoints at the distal ends of the limbs on cardiac function in volunteers with acute hypoxia, so as to determine if its actions are realized by way of segmental innervations or meridians. METHODS: Twenty healthy volunteers were divided into control, Quze (PC 3), Shousanli (LI 10), Guangming (GB 37) and Zusanli (ST 36) groups (both PC 3 and LI 10 are innervated by spinal C3-C6, and both ST 36 and GB 37 innervated by L5-S1). Acute hyoxia (simulating the conditions of about 5,000 m height above the sea level) was induced by asking the volunteers to inhale low-oxygen gas mixture (10.8% O2 + 89.2% N2) for 30 min, when, the participants' cardiac output (CO), heart rate (HR), left cardiac work (LOW), left ventricular ejection time (LVET)were measured using a ICG Monitor and EA stimulation (10 Hz/20 Hz, 1-2 V) was also conducted for 20 min following inhaling low-oxygen for 10 min. RESULTS: Before low-oxygen inhale, the levels of CO, HR, LCW and LVET ratios (test value/basic value) of the control, PC 3, LI 10, ST 36 and GB 37 groups were comparable (P > 0.05). After inhaling low-oxygen gas mixture for 10 min, the levels of CO, HR, and LCW ratios were significantly increased, and the LVET ratios were notably decreased in the five groups (P < 0.05). Compared with the 10 min-low-oxygen inhale of the same one group, CO and HR ratios at both EA 10 min and 20 min in the PC 3 and ST 36 groups, LCW ratios at EA 10 min in both PC 3 and ST 36 groups were notably down-regulated (P < 0.05), while the LVET ratios of both PC 3 and ST 36 groups was significantly prolonged (P < 0.05). No significant changes of CO, HR, LCW and LVET ratios were found in the LI 10 and GB 37 groups after EA for 10 min and 20 min (P > 0.05). CONCLUSION: EA stimulation of Quze (PC 3) and Zusanli (ST 36), but not Shousanli (LI 10) and Guangming (GB 37) can lower CO, HR and LCW levels and increase LVET in volunteer subjects undergoing acute hypoxia, suggesting that the therapeutic effect of EA maybe not rely on the segmental innervations, but rather, depend on the meridians to which the acupoints belong. PMID- 26669201 TI - [Clinical Trial of Treatment of Cervicogenic Scapulohumeral Periarthritis by Red hot Needle Therapy Combined with Cupping]. AB - OBJECTIVE: To observe the therapeutic effect of red-hot needle therapy combined with cupping for cervicogenic periarthritis of shoulder. METHODS: Forty-two cases of cervicogenic periarthritis of shoulder were randomized into red-hot needle group and routine acupuncture group (n = 21). For patients of the routine acupuncture group, the filiform needles were applied to Tianzhu (BL 10), Jianjing (GB 21), Jianzhongshu (SI 15), Jianzhen (SI 9), Jianliao (TE 14), Jianyu (LI 15), Jianqian, Tianzong (SI 11) and Ashi-points on the affected side, followed by conducting cupping at the anterior and posterior regions of the affected shoulder, SI 11, GB 21 and SI 15. For patients of the red-hot needle group, the Ashi-points on the affected shoulder were punctured with cauterized filiform needles, following by performing cupping. The treatment was performed once daily and once every other day respectively for two weeks. The shoulder motor function was assessed according to the adjusted Constant-Murley test. RESULTS: After the treatment, the integrated scores of shoulder pain, shoulder-joint activities in daily living and shoulder-joint motion range were significantly increased in both groups compared with pre-treatment in the same one group (P < 0.05) and obviously higher in the red-hot needle group than in the routine acupuncture group (P < 0.05). Of the two 21 cases of shoulder periarthritis patients in the routine acupuncture and red-hot needle groups, 4 and 8 were cured, 14 and 12 experienced improvement, 3 and 1 was invalid, with the effective rates being 85.71% and 95.24%, respectively. The therapeutic effect of the red-hot needle therapy was significantly superior to that of the routine acupuncture (P < 0.05). CONCLUSION: The red-hot needle therapy combined with cupping is effective in relieving cervicogenic shoulder periarthritis and is remarkably superior to routine acupuncture combined with cupping in improving shoulder periarthritis patients' symptoms. PMID- 26669200 TI - [Randomized Controlled Clinical Trial for Analyzing Effect of "Spleen-Stomach Regulation Nee- dling" on Oxidative Stress Level in Patients with Diabetic Nephropathy]. AB - OBJECTIVE: To observe the effect of "spleen-stomach needling" on changes of plasma malondialdehyde. (MDA), protein carbonyl (PCO, an oxidative stress damage biomaker), 8-hydroxyguanine (8-OHdG, an indicator of oxidative DNA damage) and the activity of superoxide dismutase (SOD) levels in patients with diabetic nephropathy, so as to explore its mechanisms underlying improving diabetic nephropathy. METHODS: Diabetic nephropathy patients were randomized into routine acupuncture (control) group (n = 72) and spleen-stomach needling (observation) group (n = 70) according to a random digits table and by using multi-centers, randomized and blind methods in the present study. All the patients were received routine medication. In addition, patients of the control group were treated by acupuncture stimulation of Shenshu (BL 23), Taixi (KI 3), Sanyinjiao (SP 6), Yanglingquan (GB 34), Xuanzhong (GB 39), Guanyuan (CV 4), Shousanli (LI 10), Waiguan (TE 5), Yangxi (LI 5), Liangqiu (ST 34), Shangjuxu (ST 37), Neiting (ST.44), Huaroumen (ST 24), and Dachangshu (BL 25), and those of the observation group treated by acupuncture stimulation of Zhongwan (CV 12), Quchi (LI 11), HQgu (LI 4), Xuehai (SP 10), Zusanli (ST 36), Yinlingquan (SP 9), Fenglong (ST 40), Diji (SP 8), Sanyinjiao (SP 6),Taichong (LR 3), Gaohuang (BL 43), Shenshu (BL 23), Baihuanshu (BL 30) and Zhongji (CV 3) with spleen-stomach needling method. The treatment of both groups was conducted twice a day for six weeks except Sundays. Plasma MDA, PCO and 8-OHdG contents were detected by using ELISA, and SOD detected using xanthine oxidase method. RESULTS: After 3 weeks' treatment, plasma MDA, PCO and 8-OHdG contents were significantly increased in both control and observation groups, and plasma SOD was obviously reduced in both groups (P < 0.05). No significant differences were found between the two groups in the plasma MDA, PCO and 8-OHdG contents (P > 0.05). While after 6 weeks' treatment, plasma MDA, PO and 8-OHdG contents were significantly decreased (turning to the normal levels) and plasma SOD level in the observation group was significantly up regulated (P < 0.01). Following 3 weeks' treatment, of the 72 and 70 patients in the control and observation groups, 10 and 20 cases experienced marked improvement, 22 and 15 were improved, and 40 and 35 invalid, respectively. After 6 weeks' treatment, of the 72 and 70 patients in the control and observation groups, 12 and 39 experienced marked improvement, 28 and 20 cases were improved, 32 and 11 invalid, respectively. The therapeutic effect of the observation group was obviously superior to that of the control group (P < 0.01). CONCLUSION: Acupuncture treatment with spleen-stomach regulation needling can down-regulate plasma MDA, PCO, 8-OHdG contents and up-regulate SOD activity in diabetic nephropathy patients, which may contribute to its effect in improving the patients' symptoms probably by resisting the oxidative stress damage. PMID- 26669202 TI - ["Santong Needling" by Stages for Moderate and Severe Peripheral Facial Paralysis in the Acute Period]. AB - OBJECTIVE: To observe clinical effects of "Santong needling" by stages for patients with moderate and severe peripheral facial paralysis (PFP) in the acute period. METHODS: Sixty patients with moderate and severe PFP were equally and randomly divided into Santong needling group and control group. The patients of the Santong needling group were treated by shallow puncture of Yifeng (TE 17, on the affected side) and Hegu (LI 4, on the healthy side) without needle manipulation in the acute stage ("Qing-tong", mild dredging) , by oblique penetrative puncture of Dicang (ST 4) to Jiache (ST 6), etc. , and moderate manipulation of needles in the resting stage ("Qiang-tong", stronger dredging) , and by oblique-penetrative puncture of Dicang (ST 4) to Jiache (ST 6), etc., and reinforcing needling manipulation in the recovery stage("Bu-tong", tonifying dredging). The patients of the control group were treated by "Jingjin" (musculotendon) puncture of the same acupoints. The treatment was conducted once daily, 5 times per week for 6 weeks. The 0-3-grade scores of therapeutic effects were evaluated according to the severity of the patients' symptoms and signs (including forehead stripes, palpebral fissure, nasolabial groove, drooping of the mouth angle, bulging cheek-air leak, food residue, dysgeusis, hyperacusi, lacrimation, and orbicularis oculi reflex). The therapeutic effect index = (score of pre-treatment--score of post-treatment)/score of pre-treatment x100% . The patients' life quality scores were assessed by using the World Health Organization Quality of Life (WHOQOL)-BREF questionnaire. RESULTS: After the treatment, the scores of clinical symptoms and signs were significantly decreased in both control and Santong needling groups in comparison with pre-treatment in the same one group (P < 0.05), suggesting an improvement of facial nerve function after 6 weeks' treatment. Of the two 30 patients in the control group and Santong needling group, 11 (36.7%) and 15 (50.0%) were cured, 8 (26.7%) and 9 (30.0%) experienced marked improvement, 5 (16.6%) and 4 (13.3%) were effective, and 6 (20.0%) and 2 (6.7%) invalid, with the effective rates being 80.0% and 93.3%, respectively. The therapeutic effect of Santong needling group was evidently superior to that of the control group (P < 0.05). Three-months' follow up showed that the WHOQOL-BREF scores were comparable between pre- and post-treatment in the same one group and between the two groups (P > 0.05). CONCLUSION: Santong needling by stages is effective in improving clinical symptoms and signs of patients with moderate and severe peripheral facial paralysis. PMID- 26669203 TI - [Analysis on Current State of Acupuncture Clinical Trials with Sham Acupuncture Design in Western Countries]. AB - The design of "sham acupuncture" is necessary in clinical trials of acupuncture for confirming its effectiveness in the treatment of different disorders. The authors of the present paper made a comprehensive analysis on "sham acupuncture"or "placebo acupuncture" in clinical trials of acupuncture therapy in western countries from 1) the definition and background of sham acupuncture, 2) current state of acupuncture clinical trials with sham acupuncture design in different countries, 3) current situations of acupuncture clinical trials with sham acupuncture design in Germany, and 4) current state of large sample, randomized controlled clinical trials of acupuncture therapy with sham acupuncture design in other western countries. The authors of the present paper also make an analysis on the developing trends of acupuncture clinical trials with sham acupuncture design and put forward some problems existing in current acupuncture researches. PMID- 26669204 TI - [Development of Researches on the Underlying Mechanism of Acupuncture Stimulation of Baliao-points for Improving Outlet Obstruction Constipation]. AB - Outlet obstruction constipation (OOC) is a common clinical problem affecting many people's daily life quality nowadays. Acupuncture therapy is effective in easing OOC to reduce patients' sufferings by stimulation of Baliao-points i. e., bilateral Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34), which has been confirmed repeatedly in clinical practice. In the present paper, the authors reviewed development of studies on the underlying mechanisms of acupuncture stimulation of Baliao-points for OOC from: 1) lowering the sensitivity of intraganglionic laminar nerve endings (rIGLEs) to rectal mechanical distension during defecation, 2) raising the level of circulating cholecystokinin (CCK) to improve the sensory threshold of the rectum, 3) lowering the excitability of gamma-motor neurons in the spinal anterior horns controlling the slow contraction of the rectal sphincter muscle, 4) inhibiting the excitability of sympathetic output from the spinal lateral horns, 5) easing the tonic contraction of the pelvic muscles to reduce the release of 5-hydroxy tryptamine (5-HT), histamine, and other related chemical mediators due to local ischemia. Moreover, further study on the mechanism of acupuncture stimulation of Baliao-points underlying improving OOC may help up find more specific and effective therapeutic targets and provide more reliable experimental foundation and theoretical basis. PMID- 26669205 TI - Simultaneously Harvesting Thermal and Mechanical Energies based on Flexible Hybrid Nanogenerator for Self-Powered Cathodic Protection. AB - Metal corrosion occurs anytime and anywhere in nature and the corrosion prevention has a great significance everywhere in national economic development and daily life. Here, we demonstrate a flexible hybrid nanogenerator (NG) that is capable of simultaneously or individually harvesting ambient thermal and mechanical energies and used for a self-powered cathodic protection (CP) system without using an external power source. Because of its double peculiarities of both pyroelectric and piezoelectric properties, a polarized poly(vinylidene fluoride) (PVDF) film-based NG was constructed to scavenge both thermal and mechanical energies. As a supplementary, a triboelectric NG was constructed below the pyro/piezoelectric NG to grab ambient mechanical energy. The output power of the fabricated hybrid NG can be directly used to protect the metal surface from the chemical corrosion. Our results not only verify the feasibility of self powered CP-based NGs, but also expand potential self-powered applications. PMID- 26669206 TI - AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea. AB - RATIONALE: Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) alpha1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress. OBJECTIVES: We investigated whether AMPK-alpha1 and/or AMPK-alpha2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency. METHODS: We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK alpha1 and/or AMPK-alpha2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem. MEASUREMENTS AND MAIN RESULTS: AMPK-alpha1 and AMPK-alpha2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-alpha1 and AMPK-alpha2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-alpha1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei. CONCLUSIONS: AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal. PMID- 26669207 TI - Complete donor chimerism is a prerequisite for the effect of Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) on acute graft-versus-host disease. AB - Predicted indirectly recognizable HLA epitopes (PIRCHE) computationally predict donor T-cell recognition of mismatched-HLA derived peptides following allogeneic haematopoietic stem-cell transplantation (allo-HSCT), as is evidenced by the correlation between presence of HLA-DPB1-derived PIRCHE and the occurrence of graft-vs.-host disease (GVHD). Complete donor T-cell chimerism associates with an increased GVHD risk compared to mixed patient and donor chimerism. If the correlation between the presence of PIRCHE and GVHD occurrence is indeed mediated by donor T cells, the presence of donor T cells should be required to observe such a correlation. This study was initiated to investigate whether the effect of PIRCHE is different in patients with complete chimerism compared to those with mixed chimerism. Indeed, the correlation between PIRCHE and GVHD is present in patients with complete chimerism, whereas it is absent in those with mixed chimerism. The data presented here suggest that chimerism status is important for the detection of potential GVHD epitopes. PMID- 26669209 TI - Care of Adults With Intellectual and Developmental Disabilities: Foreword. PMID- 26669210 TI - Care of Adults With Intellectual and Developmental Disabilities: Developmental Disabilities. AB - Approximately 4.8% of individuals in the United States are affected by developmental disabilities (DDs). These individuals have a spectrum of abilities in terms of communication, mobility, and activities of daily living (ADLs). Because there typically is no specific treatment for the underlying disability, the focus of care should be on diagnosing and managing co-occurring medical and mental or behavioral health conditions and improving function and quality of life. Care of patients with DDs is similar to care of patients without DDs, although adjustments may be needed in the physician's interactive approach, engagement of caregivers, and sensitivity to symptoms. Health care can be enhanced by obtaining information about caregivers and guardians, living and work situations, support services received, and functional and instrumental ADL levels. In managing acute conditions, physicians should assess change from baseline and identify and manage maladaptive behaviors that interfere with care. An individualized preventive care plan should be created that may include additional or adapted screening. Needs for consent/medical decision-making support should be identified and addressed, and consent obtained as appropriate. Providing caregiver support and becoming familiar with community resources are other aspects of caring for this population. PMID- 26669211 TI - Care of Adults With Intellectual and Developmental Disabilities: Down Syndrome. AB - Down syndrome (DS) is a genetic disorder involving excess genetic material from chromosome 21. The incidence of DS is increasing, and the life expectancy for individuals with DS has increased to a median age of 55 years. Adults with DS are at increased risk of several conditions, including significant neurologic, cardiovascular, pulmonary, gastrointestinal, musculoskeletal, endocrine, psychiatric, hematologic, and social comorbidities, and additional screening or monitoring may be needed. Additional preventive measures for patients with DS include regular screening for thyroid dysfunction, hearing loss, eye disorders, heart disease, osteoporosis, and dementia, and one-time vaccination with the polyvalent pneumococcal polysaccharide vaccine (PPV23). Quality of life should be the main focus of treatment, with patients being involved in medical decisions as much as possible. PMID- 26669208 TI - Modulation of hepcidin to treat iron deregulation: potential clinical applications. AB - The secreted peptide hormone hepcidin regulates systemic and local iron homeostasis through degradation of the iron exporter ferroportin. Dysregulation of hepcidin leads to altered iron homeostasis and development of pathological disorders including hemochromatosis, and iron loading and iron restrictive anemias. Therapeutic modulation of hepcidin is a promising method to ameliorate these conditions. Several approaches have been taken to enhance or reduce the effects of hepcidin in vitro and in vivo. Based on these approaches, hepcidin modulating drugs have been developed and are undergoing clinical evaluation. In this article we review the rationale for development of these drugs, the data concerning their safety and efficacy, their therapeutic uses, and potential future prospects. PMID- 26669212 TI - Care of Adults With Intellectual and Developmental Disabilities: Cerebral Palsy. AB - Cerebral palsy (CP) is a group of disorders that primarily affect motor function. This developmental disability is becoming more common in adults as life expectancy increases for individuals with CP. Many physical, medical, mental, and behavioral health conditions are associated with CP, and assistance should be provided to patients with CP to optimize function, when available. These comorbidities include intellectual disabilities, seizures, muscle contractures, abnormal gait, osteoporosis, communication disorders, malnutrition, sleep disorders, and mental health disorders, such as depression and anxiety. The physician should be familiar with screening for and assisting patients with these issues. Optimizing quality of life requires individualized care plans that may include physical therapy, muscle relaxants, surgery, and nutritional support. Other issues to be addressed include methods to facilitate employment; sexual concerns; and support through local and national organizations for patients, families, and caregivers. PMID- 26669213 TI - Care of Adults With Intellectual and Developmental Disabilities: Traumatic Brain Injury. AB - Traumatic brain injuries (TBIs) manifest in various forms and severities, and patients with TBIs can have multiple physical and psychological comorbidities. The physician should be prepared to assess effects of the injury and associated comorbidities, and provide needed social support. Common comorbidities include cognitive changes; epilepsy; chronic pain; headache; sleep disorders; neuroendocrine disorders; dizziness and balance issues; substance abuse; depression and anxiety; dementia; and behavioral disturbances, such as aggression. Early severity and cognitive assessment after TBI is key. For patients with mild TBIs, short-term management focuses on cognitive rest, symptom management, and gradual return to regular activities. Short-term management of patients with moderate to severe TBI often requires intensive care unit admission, early psychological consultation, and use of mannitol and probiotics. Long-term care includes monitoring and managing of the physical, behavioral, emotional, and psychological comorbidities that commonly occur in patients with TBIs. Assisting patients in accessing community and government resources can be crucial for improving their independence and quality of life. PMID- 26669215 TI - Sex differentials in caries frequencies in Medieval London. AB - OBJECTIVE: Tooth decay is one of the most common oral infections observed in skeletal assemblages. Sex differentials in caries frequency are commonly examined, with most studies finding that females tend to have a higher frequency of carious lesions (caries) compared to males. Less research has examined differences in caries between males and females with respect to age in past populations. Findings from living populations indicate that caries frequencies are higher in females, at least in part, because of the effects of estrogen and pregnancy. We are interested in the interaction of age, sex, and caries in medieval London, during a period of repeated famines, which might have exacerbated underlying biological causes of caries sex differentials. DESIGN: We examined caries in adults from two medieval London cemeteries dating to c. 1120 1539 AD: St. Mary Spital (n=291) and St. Mary Graces (n=80) to test the hypothesis that males and females have different caries frequencies irrespective of age. The association between maxillary molar caries and sex was tested using hierarchical log-linear analysis to control for the effects of age on caries frequencies. RESULTS: The results indicate a higher frequency of maxillary molar caries in females (P<0.00), and that the age distribution of caries differs between the sexes (P=0.01), with a consistent increase in frequency with age for females until late adulthood, but not males. CONCLUSIONS: The difference in caries frequencies is not explained by differences in the age distributions of the sexes. Differences in the age patterns of caries for males and females could be the result of biological factors that present during reproductive age, differences in diet, or differential access to resources during famine. PMID- 26669216 TI - Investigation of dodecane in three-dimensional porous graphene sponge by Raman mapping. AB - Three-dimensional (3D) carbon nano-materials, e.g. a graphene sponge (GS) are promising candidates for the removal of pollutants and the separation of oil and water. A systematic study on how oils or organic solvents disperse in the porous structures of 3D carbon nano-materials, and the factors affecting their sorption process, would be beneficial for designing a superior sorbent with desirable porous structures. Here, confocal Raman spectroscopic imaging was utilized to explore the absorption and desorption processes of dodecane (a constituent in petroleum products) in 3D porous GS with different pore size. It was found that dodecane predominately locates within the interior pores composed of reduced graphene oxide (rGO) sheets, which provide storage spaces for the absorbed molecules. The larger pore GS has a higher absorption capacity and faster desorption rate compared to the smaller one, which is due to the higher pore volume and weaker interaction with the absorbed molecules. A possible mechanism was also proposed to explain the role of porous macrostructures on the absorption and desorption properties of GSs. PMID- 26669214 TI - The imbalance of masticatory muscle activity affects the asymmetric growth of condylar cartilage and subchondral bone in rats. AB - OBJECTIVE: To examine the effects of imbalance of masticatory muscle activity of the rat mandible on the condylar cartilage and subchondral bone during the growth period. DESIGN: Forty 5-week-old male Wistar rats were randomly divided into experimental (n=20) and control (n=20) groups. In the experimental group, the left masseter muscles were resected. The rats were sacrificed at 7 or 9 weeks of age in both groups. Microcomputed tomography was used to determine the three dimensional morphology and cancellous bone structure. For histological and histochemical examination, 5-MUm-thick serial frontal sections of the condyle were stained with toluidine blue and immunostained with asporin and TGF-beta1 to evaluate the promotion and inhibition of chondrogenesis. RESULTS: In the experimental group, microcomputed tomography analysis showed asymmetric growth; the resected side condyles showed degenerative changes. Histological analysis showed that the total cartilage in the central region of the resected side was significantly thinner than in the non-resected side in the experimental group, as well as in the control group. Compared with the control group, the expression of asporin was significantly higher in the resected side, and significantly lower in the non-resected side. In contrast, the expression of TGF-beta1-immunopositive cells in the non-resected side was significantly higher than in the resected side and the control group. CONCLUSIONS: These findings imply that lateral imbalance of masseter muscle activity lead to inhibition of chondrogenesis and induce asymmetric formation of the condyle during the growth period. PMID- 26669217 TI - Guest editorial for the Special Issue from the Eleventh Keele Meeting on Aluminium. PMID- 26669218 TI - Hydrogenation-Induced Structure and Property Changes in the Rare-Earth Metal Gallide NdGa: Evolution of a [GaH]2- Polyanion Containing Peierls-like Ga-H Chains. AB - The hydride NdGaH1+x (x ~ 0.66) and its deuterized analogue were obtained by sintering the Zintl phase NdGa with the CrB structure in a hydrogen atmosphere at pressures of 10-20 bar and temperatures near 300 degrees C. The system NdGa/NdGaH1+x exhibits reversible H storage capability. H uptake and release were investigated by kinetic absorption measurements and thermal desorption mass spectroscopy, which showed a maximum H concentration corresponding to "NdGaH2" (0.93 wt % H) and a two-step desorption process, respectively. The crystal structure of NdGaH1+x was characterized by neutron diffraction (P21/m, a = 4.1103(7), b = 4.1662(7), c = 6.464(1) A, beta = 108.61(1) degrees Z = 2). H incorporates in NdGa by occupying two distinct positions, H1 and H2. H1 is coordinated in a tetrahedral fashion by Nd atoms. The H2 position displays flexible occupancy, and H2 atoms attain a trigonal bipyramidal coordination by centering a triangle of Nd atoms and bridging two Ga atoms. The phase stability and electronic structure of NdGaH1+x were analyzed by first-principles DFT calculations. NdGaH1H2 (NdGaH2) may be expressed as Nd(3+)(H1(-))[GaH2](2-). The two-dimensional polyanion [GaH](2-) features linear -H-Ga-H-Ga- chains with alternating short (1.8 A) and long (2.4 A) Ga-H distances, which resembles a Peierls distortion. H2 deficiency (x < 1) results in the fragmentation of chains. For x = 0.66 arrangements with five-atom moieties, Ga-H-Ga-H-Ga are energetically most favorable. From magnetic measurements, the Curie-Weiss constant and effective magnetic moment of NdGaH1.66 were obtained. The former indicates antiferromagnetic interactions, and the latter attains a value of ~3.6 MUB, which is typical for compounds containing Nd(3+) ions. PMID- 26669219 TI - Post-Chemotherapy Robotic Retroperitoneal Lymph Node Dissection: Institutional Experience. AB - PURPOSE: There is little literature on robotic retroperitoneal lymph node dissection (RRPLND) in the difficult post-chemotherapy (PC) setting. We report on the outcome of RRPLND in patients with PC-residual masses. MATERIALS AND METHODS: Between 2011 and 2015, we performed 12 PC-RRPLND. Mean patient age was 37.8 years. Mean body mass index was 30.78. Nine (75%) patients had nonseminomatus germ cell tumor (NSGCT) and three (25%) patients had seminoma tumors. Cancer stage was III in six (50%), II-C in three (25%), II-B in two (16.7%), and II-A in one (8.03%). International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification in the NSGCT was good in six, intermediate in two, and poor in one, and was good in the three seminoma patients. RESULTS: The procedure was completed effectively in 11 (91.7%) patients. Mean operative time was 312 minutes. The mean estimated blood loss was 475 mL. Mean hospital stay was 3.2 days. Mean number of lymph node excised was 12. Six of the excised masses were >=5 cm (N3), largest was 7.5 cm. Pathology showed teratoma in five (45.5%), benign/necrosis in five (45.5%), and viable germ cells in one (9%). Major complication (Clavien >=3) occurred in one patient and minor (Clavien <=2) in two. Antegrade ejaculation was preserved in eight patients and in one could not be assessed. At a median follow-up of 31 months, no infield or outfield relapses occurred. CONCLUSIONS: Robotic PC-retroperitoneal lymph node dissection (RPLND) is technically feasible and with acceptable morbidity. It is associated with low blood loss and short hospital stay. More research is needed to assess the long term outcome and to compare standard open RPLND. PMID- 26669220 TI - [Surgical treatment of chronic non-insertional Achilles tendinopathy in runners using bipolar radiofrequency]. AB - OBJECTIVE: To present the surgical technique with release of peritendon and radiofrequency as an effective treatment for athletes with chronic tendinopathy of the Achilles tendon body. MATERIALS AND METHODS: This is a retrospective case series descriptive type study. The series consists of 17 Achilles tendon surgeries in 13 patients, who habitually run. The study included patients with non-insertional Achilles tendinopathy refractory to conservative treatments. After a minimum follow-up of 12 months, clinical improvement of the athletes was assessed using the Nirschl pain scale, as well as athletic performance. RESULTS: An improvement was obtained in 94% of symptoms and a return to the previous performance in of 70% of cases in the 12 months follow-up. DISCUSSION: Peritendon release combined with bipolar radiofrequency is presented as an effective solution in this condition, for which there is currently no consensus on the best treatment. In patients in whom, after an appropriate conservative treatment for a sufficient period (at least 6 months) the non-insertional Achilles tendinopathy persists, open adhesiolysis combined with bipolar radiofrequency is a safe and with a high success rate clinical and functional intervention. In high performance athletes this technique allows a return to previous activity in a high percentage of cases. PMID- 26669222 TI - What Does it Take to Achieve Recovery for Persons With Severe Mental Illness Co occurring With Substance Use Disorders? PMID- 26669221 TI - Outbreaks of Vancomycin-Resistant Enterococci in Hospital Settings: A Systematic Review and Calculation of the Basic Reproductive Number. AB - BACKGROUND: Vancomycin-resistant enterococci (VRE) have spread worldwide. OBJECTIVE: To systematically review VRE outbreaks and estimate the pooled basic reproductive rate (R0) of VRE. METHODS: Eligible studies criteria were (1) published within 10 years, (2) report outbreak details, (3) involve 1 center, (4) estimate epidemic duration, and (5) concern adults. Descriptive analysis included number of index cases, secondary cases, and screened patients; infection control measures; and definition of contact patients. R0 was estimated by the equation R 0=(ln2) D/t d+1, with D as the generation time and t d as the doubling time. RESULTS: Thirteen VRE outbreaks were retained from 180 articles and, among them, 10 were kept for R0 calculation. The mean (range) number of index cases was 2.3 (1-8) and the mean (range) number of secondary cases was 15 (3-56). The mean (range) number of screened patients was 174 (32-509), with pooled VRE prevalence of 5.4% (95% CI, 4.5%-6.3%). Contact precautions were reported in 12 studies (92%), wards were closed in 7 (54%), with cohorting in 6 (46%). Two major screening policies were implemented: (1) a surveillance program in the unit or hospital (7 studies [54%]) and (2) screening of selected contact patients (6 studies [46%]). The pooled R0 of VRE was 1.32 (interquartile range, 1.03-1.46). CONCLUSION: We discerned considerable heterogeneity in screening policies during VRE outbreaks. Pooled R 0 was higher than 1, confirming the epidemic nature of VRE. PMID- 26669223 TI - Substance Abuse Policy Among Nursing Students: A Scoping Review. AB - BACKGROUND: Nursing students practicing in healthcare settings may increase risks to consumers, if impaired by drugs and/or alcohol, and are incapable of practicing safely. Several agencies implemented educational/professional policies, designed to protect healthcare consumers from risks. Policies addressing impaired nursing students vary among these agencies, and no nationally implemented policy exists for the treatment of impaired nursing student practice in the United States. PURPOSE: This scoping study synthesizes substance abuse policy among nursing students, guided by the research question: What professional and state policies exist to address substance abuse among U.S. nursing students? The broader term, substance abuse, was used because alcohol-specific policies were not identified. METHODS: Evidence was drawn from several policy documents identified through electronic sources that include national nursing organizations (NNOs) and nurse practice acts (NPAs) and rules. A comparative analysis was conducted on the identified policies to determine similarities and differences at the national and state levels and between national and state levels. RESULTS: Four NNO policies, 50 U.S. states, District of Columbia, and two U.S. territories' NPAs were selected for review based on selection criteria. Six areas were identified in NNO policies, and four were identified in NPAs that addressed chemically impaired nursing students. CONCLUSIONS: This review of current policy provided evidence that identifies and describes areas of concern. Impaired nursing practice, which includes nursing students, remains a major issue, complicated by the inconsistencies noted particularly within the reviewed NPAs. Knowledge gained from this review will be used to guide future research and subsequent state policy development. PMID- 26669224 TI - Association Between Smoking and Suicidal Behaviors Among Adolescents in the Republic of Korea. AB - Smoking and suicidal behaviors are significant health problems in adolescence. To address these two important health problems in youth, it is critical to understand the associations between them. Thus, this study aimed to explore the relationships between smoking and suicidal behaviors in adolescence. This study analyzed secondary data obtained from a national survey of Korean adolescents (i.e., the 7th Korea Youth Risk Behavior Web-Based Survey). Respondents were divided into two samples (38,474 middle school students and 37,169 high school students). In each sample, sample characteristics, smoking behaviors, and suicidal behaviors were examined using descriptive statistics (means and frequencies). The associations between smoking and suicidal behaviors were investigated using multivariate logistic regression analyses. To obtain more accurate findings, the complex sampling design employed in the national survey was incorporated in the analyses. Lifetime smokers and daily smokers made up 20% and 13% of the middle school sample and 32% and 29% of the high school sample, respectively. In both samples, of the three suicidal behaviors, the proportion of suicidal ideation was the greatest (20%), followed by suicide plans (6%-8%) and suicide attempts (4%-5%). This study revealed statistically significant associations between smoking and suicidal behaviors. Furthermore, most analyses revealed noncausal dose-related associations between these behaviors. On the basis of the study findings, health professionals should implement concurrent strategies targeting both smoking and suicidal behaviors rather than focus on them separately to address related health problems. PMID- 26669225 TI - Outcomes of a One-Time Telephone Intervention for Smoking Cessation in Adults. AB - Tobacco use is the single greatest cause of disease and premature death in America today. To address this major public health concern, states are required to provide smoking cessation services. The purpose of this article is to examine the effectiveness of a one-time telephone adult smoking cessation program designed by a certified addictions registered nurse-advanced practice and conducted over an 11-month period by the State of Nevada. Specifically, the program included a telephone-based counseling session and distribution of a 2 week supply of nicotine replacement therapy patches. The sample population consisted of 1471 Nevada residents, men and women, aged 18 years and over who called the Quitline for smoking cessation help. All participants in the program provided consent for a follow-up call to report on their quit rates and satisfaction with the intervention at 7 months postintervention. Although everyone who participated in the interventions was called, only 373 (25.4%) were actually reached via telephone contact. Of this group, quit rates showed that 34.6% reported continuous abstinence at 7 months, whereas 35.1% were abstinent at the 7-day point prevalence and 31.9% were abstinent at the 30-day point prevalence. Patient satisfaction with the program revealed that 87.6% (n = 373) of the participants reported being very or mostly satisfied. This program evaluation study shows that short-duration telephone counseling plus nicotine replacement therapy was associated with helping at least one third of the participants to quit using tobacco for all of the prevalence points-7 and 30 days and at 7 months postintervention. PMID- 26669227 TI - Fighting Prescription Drug Abuse Through State Policy: The Role of Nursing in Successful Implementation. AB - Prescription drug abuse has become a top public health concern in the United States in recent years. Changes in prescribing practices and the way in which health providers manage pain resulted from national quality improvement efforts in the 1990s. Most efforts to reduce morbidity and mortality associated with the prescription drug abuse epidemic occur through policy initiatives at the state level. In 2011, Indiana ranked 17th in the United States and had only implemented a few intervention and prevention strategies. However, through a coordinated effort within the state, Indiana has expanded Good Samaritan laws and adopted rescue drug policies. Furthermore, the nursing workforce in Indiana has played a critical role in the successful implementation of these new policies. Nurses across the state have provided education and training to first responders and lay persons. They have also consulted with law enforcement agencies and other organizations looking to fully leverage the potential of these new state policies. Because of their versatility and clinical expertise, the nursing workforce has and will continue to play a critical role in the successful implementation of state policy initiatives aimed at fighting the prescription drug abuse epidemic. PMID- 26669226 TI - Different Subjective and Objective Responses to Alcohol Among Heavy and Light Drinkers of Han and Uyghur Nationalities in China. AB - OBJECTIVE: Given the observed differences in alcohol consumption characteristics between the Han and Uyghur nationalities in clinical reports and in daily life, the subjective and objective responses to alcohol in heavy drinkers (HDs) and light drinkers (LDs) in the Han and Uyghur nationalities in China were compared. METHODS: A within-subject, double-blind, placebo-controlled human laboratory paradigm was performed. Each subject completed three experimental sessions in random order. Biphasic Alcohol Effects Scale and Positive and Negative Affect Schedule scales were administered, and heart rate (HR), blood pressure, and salivary cortisol levels were measured at predrink baseline and 30, 60, 120, and 180 minutes after the initial alcohol beverage consumption. RESULTS: Compared with LDs, HDs exhibited higher stimulation, positive affect, and lower sedation in both ethnicities. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation than Uyghur drinkers after consumption of alcohol. Moreover, HDs exhibited more HR increase during the ascending limb of breath alcohol content (p < .05) and less cortisol level during the declining limb of breath alcohol content (p < .05). Both HDs and LDs exhibited decreased systolic and diastolic pressures for both high- and low-dose beverages (ps < .01). CONCLUSION: Compared with LDs, HDs exhibited more HR increase and lower salivary cortisol level after alcohol consumption. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation after consumption of alcohol as compared with Uyghur drinkers. This modality of subjective and physiological responses to alcohol in the Han and Uyghur ethnicities is similar. PMID- 26669228 TI - The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence. AB - The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits. PMID- 26669230 TI - EVZIO: A New Delivery System for Naloxone. PMID- 26669231 TI - Harm Reduction Among Youth in Australia: An Interview With Alison Hutton. PMID- 26669234 TI - Size-confined growth of atom-precise nanoclusters in metal-organic frameworks and their catalytic applications. AB - Using MOFs as size-selection templates, we have for the first time synthesized atom-precise Au11:PPh3 nanoclusters (NCs) and Au13Ag12:PPh3 NCs with high purity by a one-step, in situ reduction method. Specifically, we found that the product released from the frameworks of ZIF-8 is exclusively the Au11:PPh3 NCs rather than polydispersed NCs, and inside MIL-101(Cr) the Au13Ag12:PPh3 NCs constitute the exclusive product. The metal NC@MOF composites are also demonstrated for catalytic application. The high catalytic efficiency for the oxidation of benzyl alcohol indicates that atom-precise noble metal NCs@MOFs may act as a promising class of heterogeneous catalysts. The atom-precise NCs obtained in the MOF templated synthesis imply the future possibility of using MOFs of various pore sizes for the size-selective synthesis of atomically precise NCs. Meanwhile, metal NCs@MOFs will contribute to the understanding of the mechanism of nanocatalyst surface reactions and hence opens up enormous opportunities in heterogeneous catalysis. PMID- 26669242 TI - Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. AB - BACKGROUND: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. METHODS: A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. RESULTS: We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. CONCLUSIONS: This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis. PMID- 26669244 TI - Clinical findings and effect of sodium hydrogen carbonate in patients with glutathione synthetase deficiency. AB - BACKGROUND: Glutathione synthetase (GS) deficiency is a rare inborn error of glutathione (GSH) metabolism manifested by severe metabolic acidosis, hemolytic anemia, neurological problems and massive excretion of pyroglutamic acid (5 oxoproline) in the urine. The disorder has mild, moderate, and severe clinical variants. We aimed to report clinical and laboratory findings of four patients, effect of sodium hydrogen carbonate treatment and long-term follow up of three patients. METHODS: Urine organic acid analysis was performed with gas chromatography-mass spectrometry. Molecular genetic analysis was performed in three patients, mutation was found in two of them. Enzyme analysis was performed in one patient. Clinical and laboratory findings of four patients were evaluated. RESULTS: One patient died at 4 months old, one patient's growth and development are normal, two patients have developed intellectual disability and seizures in the long term follow up period. Three patients benefited from sodium hydrogen carbonate treatment. CONCLUSIONS: The clinical picture varies from patient to patient, so it is difficult to predict the prognosis and the effectiveness of treatment protocols. We reported long term follow up of four patients and demonstrated that sodium hydrogen carbonate is effective for treatment of chronic metabolic acidosis in GS deficieny. PMID- 26669243 TI - Evaluating health risk using a continuous metabolic syndrome score in obese children. AB - BACKGROUND: The metabolic syndrome (MS) in pediatrics is controversial. Rather than a dichotomous scale, a continuous metabolic syndrome score (cMets) has been proposed to evaluate MS. The aim of this study was to evaluate the utility of a cMets score among an ethnically diverse cohort of children with acanthosis nigricans (AN). METHODS: A retrospective chart review was used to extract clinical and laboratory information on a cohort of obese children. Criteria for MS components and the cMets score were established using published guidelines. Multiple linear regression evaluated the effect of AN status on MS and cMets. Fisher's exact test compared the race differential on the presence or absence of MS component disorders. RESULTS: MS diagnosis was non-significant when considering AN status (p=0.554) and ethnicity (p=0.431). Evaluation of the frequency of component disorders, revealed that Caucasians had significantly higher levels of abnormal triglycerides (TG) (35.1 vs. 10.3%; p<0.001), whereas African Americans had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) scores (51.3% vs. 22.3%; p<0.001). cMets was sensitive to identifying metabolic risk among Caucasians with AN, only (p=0.029). CONCLUSIONS: This study found differences in health risk among an obese, ethnically diverse sample of children. cMets is a more sensitive marker of metabolic change compared with MS, especially when AN status and race are considered. cMets may pose an opportunity for the clinician to evaluate the interaction of health risks on the health status of obese children. PMID- 26669245 TI - GPR55 - a putative "type 3" cannabinoid receptor in inflammation. AB - G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative "type 3" cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation. PMID- 26669246 TI - Protective effect of Scutellaria species on AAPH-induced oxidative damage in human erythrocyte. AB - BACKGROUND: Scutellaria baicalensis is a well-known plant in traditional Chinese medicine. Recently, several Scutellaria species with therapeutic potential have been recognized worldwide. Scutellaria colebrookiana and Scutellaria violacea, native to the Western Ghats of India, are reported to possess free radical scavenging efficacy. At present, the protective effect of these Scutellaria spp. against 2,2' azobis (2-amidinopropane) hydrochloride (AAPH)-induced oxidative damage in human erythrocytes has been analyzed. METHODS: Oxidative stress in erythrocyte was induced by AAPH. The inhibition of hemolysis, membrane lipid peroxidation, and protein damage by chloroform extracts of Scutellaria spp. was assessed biochemically. Phytochemicals of the extracts were analyzed by Fourier transform infrared spectrophotometer (FTIR). RESULTS: Approximately 95% of erythrocytes were lysed by AAPH over 3 h of incubation. Significant reduction in hemolysis was observed by the extracts, and the IC50 values were 18.3 and 23.5 MUg/mL for S. colebrookiana and S. violacea, respectively. Both the extracts were found to inhibit AAPH-induced lipid peroxidation in ghost membrane with IC50 92+/ 2.8 and 70+/-5.6 MUg/mL. In the analysis of the membrane proteins using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the AAPH-induced degradation of actin was found reduced by both the extracts. The FTIR spectrum revealed the presence of polyphenols, carboxylic acids, alkanes, and aromatic compounds in extracts. In quantitative analysis, the total polyphenolic content estimated was 380+/-0.23 and 203.7+/-1.4 mg of gallic acid equivalent per gram extract of S. colebrookiana and S. violacea. CONCLUSIONS: Results indicate that S. colebrookiana and S. violacea are capable of protecting erythrocytes from oxidative damage. This cytoprotective effect of the extract is possibly by its antioxidant property. PMID- 26669247 TI - Kinin B1 receptor mediates memory impairment in the rat hippocampus. AB - The bradykinin (BK) receptors B1R and B2R are involved in inflammatory responses and their activation can enhance tissue damage. The B2R is constitutively expressed and mediates the physiologic effects of BK, whereas B1R expression is induced after tissue damage. Recently, they have been involved with Alzheimer's disease, ischemic stroke and traumatic brain injury (TBI). In this study, we investigated the role of bradykinin in short and long-term memory consolidation (STM and LTM). It was observed that bilateral injection of BK (300 pmol/MUl) disrupted the STM consolidation but not LTM, both evaluated by inhibitory avoidance test. The STM disruption due to BK injection was blocked by the previous injection of the B1R antagonist des-Arg10-HOE140 but not by the B2R antagonist HOE140. Additionally, the injection of the B1 agonist desArg9-BK disrupted STM and LTM consolidation at doses close to physiological concentration of the peptide (2.3 and 37.5 pmol, respectively) which could be reached during tissue injury. The presence of B1R located on glial cells around the implanted guide cannula used for peptide injection was confirmed by immunofluorescence. These data imply in a possible participation of B1R in the STM impairment observed in TBI, neuroinflammation and neurodegeneration. PMID- 26669248 TI - Comparison of Retinal Sensitivity between Professional Soccer Players and Non athletes. AB - The purpose of the study was to compare the peripheral retinal sensitivity of the visual field between professional soccer players and age-gender matched non athlete subjects. All participants underwent a complete eye evaluation. The visual field was evaluated with the achromatic program 60-4 from the Humphrey automated perimetry. The binocular visual field was created with the best location model. It was divided into 4 quadrants (left superior, right superior, left inferior, and right inferior) and compared between groups. The study group comprised 29 professional male football players and the control group comprised 26 age-matched male non-athletes. Mean age was 25.8+/-4.7 years in the study group and 26.3+/-5.1 for controls. The average of retina sensitivity in the left inferior and right inferior quadrants was higher in the study group (27.2+/-1.2 dB and 27.0+/-1.4 dB) as compared to controls (26.1+/-1.9 dB and 25.5+/-2.1 dB). (Student's t test, P=0.011 and P=0.004, respectively). In this small cohort, professional soccer players presented higher retina sensitivity in the inferior quadrants when compared to non-athletes. PMID- 26669249 TI - A New Surgical Model of Skeletal Muscle Injuries in Rats Reproduces Human Sports Lesions. AB - Skeletal muscle injuries are the most common sports-related injuries in sports medicine. In this work, we have generated a new surgically-induced skeletal muscle injury in rats, by using a biopsy needle, which could be easily reproduced and highly mimics skeletal muscle lesions detected in human athletes. By means of histology, immunofluorescence and MRI imaging, we corroborated that our model reproduced the necrosis, inflammation and regeneration processes observed in dystrophic mdx-mice, a model of spontaneous muscle injury, and realistically mimicked the muscle lesions observed in professional athletes. Surgically-injured rat skeletal muscles demonstrated the longitudinal process of muscle regeneration and fibrogenesis as stated by Myosin Heavy Chain developmental (MHCd) and collagen-I protein expression. MRI imaging analysis demonstrated that our muscle injury model reproduces the grade I-II type lesions detected in professional soccer players, including edema around the central tendon and the typically high signal feather shape along muscle fibers. A significant reduction of 30% in maximum tetanus force was also registered after 2 weeks of muscle injury. This new model represents an excellent approach to the study of the mechanisms of muscle injury and repair, and could open new avenues for developing innovative therapeutic approaches to skeletal muscle regeneration in sports medicine. PMID- 26669250 TI - Reliability of Time to Exhaustion Treadmill Running as a Measure of Human Endurance Capacity. AB - Little if any research has examined the variability in time to exhaustion (TTE) during submaximal treadmill running. This study investigated the test-retest reliability of submaximal treadmill TTE as a measure of endurance capacity. 16 endurance-trained males (n=14) and females (n=2) completed a run to exhaustion at 70% VO2max (T1) and repeated the same run 3 weeks later (T2). At 30-min intervals during each run, expired gas, heart rate (HR) and ratings of perceived exertion (RPE) were collected. Mean +/- SD TTE was 96 +/- 20 min in T1 vs. 101 +/- 29 min in T2 (P=0.3). The mean +/- 95% confidence intervals (CI) of the coefficient of variance (CV) was 5.4% (1.4-9.6). The average intraclass correlation coefficient (+/- 95% CI) was 0.88 (0.67-0.96) between trials. The respiratory-exchange ratio was not different between trials, T1: 0.87 +/- 0.1 and T2: 0.89 +/- 0.1 (P>0.05) and neither was total whole-body carbohydrate oxidation (2.1 +/- 0.4 g.min(-1) and 2.3 +/- 0.6 g.min(-1)), fat oxidation (0.6 +/- 0.2 g.min(-1)), HR (178 +/- 8 and 175 +/- 7 beats.min(-1)) or RPE (17 +/- 3 and 16 +/- 3). These results suggest that use of prolonged treadmill-based TTE can be a reliable research tool to assess human endurance capacity in aerobically-trained men and women. PMID- 26669251 TI - A Correlational Analysis of Tethered Swimming, Swim Sprint Performance and Dry land Power Assessments. AB - Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and 0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers. PMID- 26669252 TI - A Negative Life Event Impairs Psychosocial Stress, Recovery and Running Economy of Runners. AB - The purpose was to investigate how a negative life event (NLE) affects perceived psychosocial stress, recovery and running economy (RE). Competitive runners were monitored in a prospective non-experimental cohort study over one full training season in which they experienced the same unplanned severe NLE. 16 runners recorded stress and recovery scores (RESTQ-Sport) every week. The average scores over 3 weeks before the NLE were used as a baseline and were compared to scores during the week of the NLE (week 0), week 1 and week 2. 7 runners completed a submaximal treadmill test before and after the NLE. Repeated measures ANOVAs revealed that most scores on general stress scales were increased in week 0 and 1. Of the general recovery scales, "general well-being" was decreased in week 0 and 1, "social" and "physical recovery" were decreased in week 0. No changes in the sport-specific stress scales were found. However, 2 of the sport-specific recovery scales were decreased in week 0. An impaired RE was shown 3 weeks after the NLE. Therefore, it is important to know what is going on in an athlete's life, because stressful life events alter RE after the stress and recovery already returned to normal levels. PMID- 26669253 TI - Frontline treatment of epithelial ovarian cancer. AB - This is a contemporaneous review of the frontline treatment of epithelial ovarian cancer (EOC), specifically on the importance of optimal surgical cytoreductive surgery, the pivotal role of platinum-based adjuvant chemotherapy (which encompasses intraperitoneal and dose-dense regimens) and the emergence of neo adjuvant chemotherapy. Additionally, the benefit of concurrent and maintenance bevacizumab in the suboptimally debullked stage III and stage IV EOC setting is also reviewed. The article also discusses the increasing importance of prognostic and predictive molecular biomarkers in the future management of EOC. PMID- 26669254 TI - Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease--systems and clinical approach. AB - The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2 year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory. PMID- 26669255 TI - Effects of Ayurvedic Oil-Dripping Treatment with Sesame Oil vs. with Warm Water on Sleep: A Randomized Single-Blinded Crossover Pilot Study. AB - OBJECTIVES: Ayurvedic oil-dripping treatment (Shirodhara) is often used for treating sleep problems. However, few properly designed studies have been conducted, and the quantitative effect of Shirodhara is unclear. This study sought to quantitatively evaluate the effect of sesame oil Shirodhara (SOS) against warm water Shirodhara (WWS) on improving sleep quality and quality of life (QOL) among persons reporting sleep problems. METHODS: This randomized, single-blinded, crossover study recruited 20 participants. Each participant received seven 30-minute sessions within 2 weeks with either liquid. The washout period was at least 2 months. The Shirodhara procedure was conducted by a robotic oil-drip system. The outcomes were assessed by the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Epworth Sleepiness Scale (ESS) for daytime sleepiness, World Health Organization Quality of Life 26 (WHO-QOL26) for QOL, and a sleep monitor instrument for objective sleep measures. Changes between baseline and follow-up periods were compared between the two types of Shirodhara. Analysis was performed with generalized estimating equations. RESULTS: Of 20 participants, 15 completed the study. SOS improved sleep quality, as measured by PSQI. The SOS score was 1.83 points lower (95% confidence interval [CI], -3.37 to -0.30) at 2 week follow-up and 1.73 points lower (95% CI, -3.84 to 0.38) than WWS at 6-week follow-up. Although marginally significant, SOS also improved QOL by 0.22 points at 2-week follow-up and 0.19 points at 6-week follow-up compared with WWS. After SOS, no beneficial effects were observed on daytime sleepiness or objective sleep measures. CONCLUSIONS: This pilot study demonstrated that SOS may be a safe potential treatment to improve sleep quality and QOL in persons with sleep problems. PMID- 26669256 TI - JNK pathway in osteosarcoma: pathogenesis and therapeutics. AB - CONTEXT: The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein 1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. OBJECTIVE: In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. RESULTS: Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. CONCLUSION: Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients. PMID- 26669257 TI - Effects of salinity and temperature on inactivation and repair potential of Enterococcus faecalis following medium- and low-pressure ultraviolet irradiation. AB - AIMS: To investigate the medium-pressure (MP) and low-pressure (LP) Ultraviolet (UV) susceptibility and the repair potential of Enterococcus faecalis (DSM 20478) after UV treatment. METHODS AND RESULTS: A range of UV doses from 4 to 19 mJ cm( 2) was selected in this study. Photoreactivation and dark repair performance were investigated under fluorescent light or in the dark respectively. The inactivation and repair performance of UV disinfection under a range of salinities (0, 1%, 3%) and temperature (4 and 25 degrees C) were compared. Results indicated that MP UV exposure resulted in higher inactivation efficiency against Ent. faecalis than LP UV exposure. For repair potential, LP UV resulted in a greater level of light repair than MP UV. Effect of salinity on the inactivation and repair of Ent. faecalis was correlated with UV sources, whereas low temperature generally adversely affected the inactivation efficiency and final repair levels after both MP and LP UV exposure. CONCLUSIONS: Both salinity and temperature demonstrated to play an important role in the inactivation and repair capability when UV light was used to treat ballast water. SIGNIFICANCE AND IMPACT OF THE STUDY: Considering that UV-treated ballast water is exposed or discharged to marine water environment in many countries with various temperature and salinity conditions, results of this study provide significant implications for the management of public health associated with ballast water treatment and discharge. PMID- 26669258 TI - Systems Approaches towards Molecular Profiling of Human Immunity. AB - Systems immunology integrates cutting-edge technologies with bioinformatics to comprehensively interrogate the immune response to infection at an organismal level. Here, we review studies that have leveraged transcriptomic, genomic, proteomic, and metabolomic approaches towards the identification of cells, molecules, and pathways implicated in host-pathogen interactions. We discuss the potential of single cell technologies for the study of human immune responses and, in this context, we advocate that systems immunology provides a conceptual and methodological framework to harness these approaches to address longstanding questions of fundamental and applied immunology. Recognizing that the field is still in its infancy, we also discuss current limitations of systems immunology, as well as the need for validation of key findings for the discipline to fulfill its promise. PMID- 26669260 TI - Droplets Can Rebound toward Both Directions on Textured Surfaces with a Wettability Gradient. AB - The impact of water droplets on superhydrophobic surfaces with a wettability gradient is studied using the lattice Boltzmann simulation. Droplets impacting such textured surfaces have been previously reported to rebound obliquely following the wettability gradient due to the unbalanced interfacial forces created by the heterogeneous architectures. Here we demonstrate that droplets can rebound toward both directions on textured surfaces with a wettability gradient. Our simulation results indicate that the rebound trajectory of droplets is determined by the competition between the lateral recoil of the liquid and the penetration and capillary emptying of the penetrated liquid from the textures in the vertical direction. When the time scale for the droplet penetration and capillary emptying process is smaller than the time for the lateral spreading, the droplet will rebound following the wettability gradient. By contrast, the droplet will display a bouncing against the wettability gradient direction because of the significant capillary penetration and emptying in the transverse direction. We believe that our study provides important insight for the design of micro/nanotextured surfaces for controlled droplet manipulation. PMID- 26669259 TI - Benzoate degradation by Rhodococcus opacus 1CP after dormancy: Characterization of dioxygenases involved in the process. AB - The process of benzoate degradation by strain Rhodococcus opacus 1CP after a five year dormancy was investigated and its peculiarities were revealed. The strain was shown to be capable of growth on benzoate at a concentration of up to 10 g L( 1). The substrate specificity of benzoate dioxygenase (BDO) during the culture growth on a medium with a low (200-250 mg L(-1)) and high (4 g L(-1)) concentration of benzoate was assessed. BDO of R. opacus 1CP was shown to be an extremely narrow specificity enzyme. Out of 31 substituted benzoates, only with one, 3-chlorobenzoate, its activity was higher than 9% of that of benzoate. Two dioxygenases, catechol 1,2-dioxygenase (Cat 1,2-DO) and protocatechuate 3,4 dioxygenase (PCA 3,4-DO), were identified in a cell-free extract, purified and characterized. The substrate specificity of Cat 1,2-DO isolated from cells of strain 1CP after the dormancy was found to differ significantly from that of Cat 1,2-DO isolated earlier from cells of this strain grown on benzoate. By its substrate specificity, the described Cat 1,2-DO was close to the Cat 1,2-DO from strain 1CP grown on 4-methylbenzoate. Neither activity nor inhibition by protocatechuate was observed during the reaction of Cat 1,2-DO with catechol, and catechol had no inhibitory effect on the reaction of PCA 3,4-DO with protocatechuate. PMID- 26669261 TI - Translesion Polymerases Drive Microhomology-Mediated Break-Induced Replication Leading to Complex Chromosomal Rearrangements. AB - Complex genomic rearrangements (CGRs) are a hallmark of many human diseases. Recently, CGRs were suggested to result from microhomology-mediated break-induced replication (MMBIR), a replicative mechanism involving template switching at positions of microhomology. Currently, the cause of MMBIR and the proteins mediating this process remain unknown. Here, we demonstrate in yeast that a collapse of homology-driven break-induced replication (BIR) caused by defective repair DNA synthesis in the absence of Pif1 helicase leads to template switches involving 0-6 nt of homology, followed by resolution of recombination intermediates into chromosomal rearrangements. Importantly, we show that these microhomology-mediated template switches, indicative of MMBIR, are driven by translesion synthesis (TLS) polymerases Polzeta and Rev1. Thus, an interruption of BIR involving fully homologous chromosomes in yeast triggers a switch to MMBIR catalyzed by TLS polymerases. Overall, our study provides important mechanistic insights into the initiation of MMBIR associated with genomic rearrangements, similar to those promoting diseases in humans. PMID- 26669262 TI - PIWI Slicing and EXD1 Drive Biogenesis of Nuclear piRNAs from Cytosolic Targets of the Mouse piRNA Pathway. AB - PIWI-interacting RNAs (piRNAs) guide PIWI proteins to suppress transposons in the cytoplasm and nucleus of animal germ cells, but how silencing in the two compartments is coordinated is not known. Here we demonstrate that endonucleolytic slicing of a transcript by the cytosolic mouse PIWI protein MILI acts as a trigger to initiate its further 5'->3' processing into non-overlapping fragments. These fragments accumulate as new piRNAs within both cytosolic MILI and the nuclear MIWI2. We also identify Exonuclease domain-containing 1 (EXD1) as a partner of the MIWI2 piRNA biogenesis factor TDRD12. EXD1 homodimers are inactive as a nuclease but function as an RNA adaptor within a PET (PIWI-EXD1 Tdrd12) complex. Loss of Exd1 reduces sequences generated by MILI slicing, impacts biogenesis of MIWI2 piRNAs, and de-represses LINE1 retrotransposons. Thus, piRNA biogenesis triggered by PIWI slicing, and promoted by EXD1, ensures that the same guides instruct PIWI proteins in the nucleus and cytoplasm. PMID- 26669263 TI - EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation. AB - Gene activation in metazoans is accompanied by the presence of histone variants H2AZ and H3.3 within promoters and enhancers. It is not known, however, what protein deposits H3.3 into chromatin or whether variant chromatin plays a direct role in gene activation. Here we show that chromatin containing acetylated H2AZ and H3.3 stimulates transcription in vitro. Analysis of the Pol II pre-initiation complex on immobilized chromatin templates revealed that the E1A binding protein p400 (EP400) was bound preferentially to and required for transcription stimulation by acetylated double-variant chromatin. EP400 also stimulated H2AZ/H3.3 deposition into promoters and enhancers and influenced transcription in vivo at a step downstream of the Mediator complex. EP400 efficiently exchanged recombinant histones H2A and H3.1 with H2AZ and H3.3, respectively, in a chromatin- and ATP-stimulated manner in vitro. Our data reveal that EP400 deposits H3.3 into chromatin alongside H2AZ and contributes to gene regulation after PIC assembly. PMID- 26669264 TI - Rat and human STINGs profile similarly towards anticancer/antiviral compounds. AB - Cyclic dinucleotides (CDNs) and antitumor/antiviral agents (DMXAA and CMA) trigger STING-dependent innate immunity activation. Accumulative evidences have showed that DMXAA and CMA selectively activate mouse, but not human STING signaling. The mechanism underlying this species selectivity remains poorly understood. In this report, we have shown that human and rat STINGs display more similar signaling profiles toward DMXAA and CMA than that of human and mouse STINGs, suggesting that rat is more suitable for preclinical testing of STING targeted drugs. We have also determined the crystal structures of both apo rat STING and its complex with cyclic GMP-AMP with 2'5' and 3'5' phosphodiester linkage (2'3'-cGAMP), a human endogenous CDN. Structure-guided biochemical analysis also revealed the functional importance of the connecting loop (A140 N152) between membrane and cytosolic domains in STING activation. Taken together, these findings reveal that rat STING is more closely related to human STING in terms of substrate preference, serving as a foundation for the development of STING-targeted drugs. PMID- 26669266 TI - Agreement between lower esophageal and nasopharyngeal temperatures in children ventilated with an endotracheal tube with leak. AB - BACKGROUND: A temperature probe placed in the lower third of the esophagus accurately reflects core temperature in anesthetized children. Temperature probes are commonly placed in the nasopharynx in children, but when utilizing an uncuffed endotracheal tube (ETT) with a softly audible leak, ventilated gases from the trachea can escape upwards toward the nasopharynx, thereby potentially causing a cooling effect in the nasopharynx. OBJECTIVES: We sought to establish if nasopharyngeal and lower esophageal temperatures are in agreement in children undergoing general anesthesia, both in scenarios of ventilation with a cuffed ETT that has minimal or no leak (cuff up), as well as an ETT with leak (cuff down). METHODS: A prospective, crossover agreement study was performed on anesthetized children. Children were intubated with a MicroCuff((r)) ETT and had temperature probes inserted into both the nasopharynx and lower esophagus. Under standardized ventilator and gas flow settings, temperatures were recorded with the ETT cuff inflated, and with the cuff deflated. Bland-Altman plots were utilized to assess agreement of temperatures. RESULTS: Fifty patients successfully completed this study. The mean difference between esophageal and nasopharyngeal temperature was found to be -0.03 degrees C in the presence of minimal or no leak around the ETT (cuff up), with 95% limits of agreement (LOA) of -0.22 to 0.15 degrees C. The mean difference between esophageal and nasopharyngeal temperature was found to be 0.1 degrees C when a larger leak existed around the ETT (cuff down), with LOA of 0.31 to 0.51 degrees C. CONCLUSIONS: Nasopharyngeal temperature accurately reflects lower esophageal temperature when there is minimal or no ETT leak. When a larger ETT leak is present, nasopharyngeal temperature is on average 0.1 degrees C cooler than lower esophageal temperature. As the nasopharyngeal temperature probe site confers the advantage of simplicity of accurate placement compared to its esophageal counterpart, our findings support the use of nasopharyngeal temperature probes in children ventilated with both cuffed and uncuffed ETTs. PMID- 26669265 TI - Ruthenium-Catalyzed Multicomponent Reactions: Access to alpha-Silyl-beta-Hydroxy Vinylsilanes, Stereodefined 1,3-Dienes, and Cyclohexenes. AB - The synthesis of densly functionized alpha-silyl-beta-hydroxyl vinylsilanes via ruthenium-catalyzed multicomponent reaction (MCR) is reported herein. Exceptionally high regio- and diastereoselectivity was achieved by employing an unprecedented hydrosilylation of bifunctional silyl-propargyl boronates. The simple protocol, mild reaction conditions, and unique tolerability of this method make it a valuable tool for the synthesis of highly elaborated building blocks. The one-pot synthesis of stereodefined olefins, the generation of a valuable cyclohexene building block through a four-component MCR, and further functionalization in an abundance of diastereoselective reactions is disclosed herein. PMID- 26669267 TI - A role for the androgen receptor in the treatment of male breast cancer. AB - Male breast cancer (BC) is relatively rare, making up less than 1% of all breast cancer cases in the United States. Treatment guidelines for male BC are derived from studies on the treatment of female BC, and are based molecular and clinical characteristics, such as hormone receptor positivity. For female estrogen receptor positive (ER+) breast cancers, the standard of care includes three classes of endocrine therapies: selective estrogen receptor modulators, aromatase inhibitors, and pure anti-estrogens. In contrast to female ER+ breast cancers, there is less known about the optimal treatment for male ER+ BC. Furthermore, in contrast to ER, less is known about the role of the androgen receptor (AR) in male and female BC. We report here the treatment of a 28-year-old man with metastatic AR+, ER+ breast cancer otherwise refractory to chemotherapy, who has had a durable clinical response to hormonal suppression with the combination of aromatase inhibition (Letrozole) in conjunction with a GnRH agonist (Leuprolide). PMID- 26669268 TI - Vibrational Spectra and Theoretical Calculations of cis- and trans-3-Fluoro-N methylaniline in the Neutral (S(0)) and Cationic (D(0)) Ground States. AB - The mass-analyzed threshold ionization spectra of jet-cooled cis- and trans-3 fluoro-N-methylaniline (3FNMA) were recorded by ionizing via the vibrationless 0(0) and various vibrational levels of the S1 state. The adiabatic ionization energies of cis- and trans-3FNMA are determined to be 61,742 +/- 5 and 61,602 +/- 5 cm(-1), respectively. In the 0-1800 cm(-1) region, most of the observed vibrations in the D0 state result from the in-plane ring deformation and substituent-sensitive modes. For the high-frequency vibration region, the infrared-ultraviolet double-resonance and autoionization-detected infrared spectroscopies were applied to investigate the N-H and C-H stretching vibrations of bare 3FNMA in the S0 and D0 states. The C-H stretching vibrational information, which we failed to obtain for the bare 3FNMA cation, is complemented by recording the infrared-photodissociation spectra of its Ar cluster cation. It is revealed that a red-shifted frequency and an enhanced intensity are observed for the N-H stretch, while blue-shifted frequencies and greatly decreased intensities are found for both aromatic and the methyl C-H stretches. The blue shift of the C-H stretches is first explained by the balance of two factors, namely, the hyperconjugative interaction and the rehybridization effect. Analysis of the vibrational frequencies reveals a correlation between the relative stability of two rotamers in different electronic states and the relative rigidity of aromatic ring, indicating a mechanism of the long-range interactions "through bond" between the substituents. The density functional theory calculations can well reproduce the vibrational spectra in both S0 and D0 states. With the experimental and theoretical data, the substitution and conformation effects on the properties of 3FNMA in the S0 and D0 states, including the molecular structures, the reactive sites of electrophilic attack, and the vibrational behaviors, were discussed in detail. PMID- 26669269 TI - An anatomy precourse enhances student learning in veterinary anatomy. AB - Veterinary anatomy is often a source of trepidation for many students. Currently professional veterinary programs, similar to medical curricula, within the United States have no admission requirements for anatomy as a prerequisite course. The purpose of the current study was to evaluate the impact of a week-long precourse in veterinary anatomy on both objective student performance and subjective student perceptions of the precourse educational methods. Incoming first year veterinary students in the Louisiana State University School of Veterinary Medicine professional curriculum were asked to participate in a free precourse before the start of the semester, covering the musculoskeletal structures of the canine thoracic limb. Students learned the material either via dissection only, instructor-led demonstrations only, or a combination of both techniques. Outcome measures included student performance on examinations throughout the first anatomy course of the professional curriculum as compared with those who did not participate in the precourse. This study found that those who participated in the precourse did significantly better on examinations within the professional anatomy course compared with those who did not participate. Notably, this significant improvement was also identified on the examination where both groups were exposed to the material for the first time together, indicating that exposure to a small portion of veterinary anatomy can impact learning of anatomical structures beyond the immediate scope of the material previously learned. Subjective data evaluation indicated that the precourse was well received and students preferred guided learning via demonstrations in addition to dissection as opposed to either method alone. Anat Sci Educ 9: 344-356. (c) 2015 American Association of Anatomists. PMID- 26669270 TI - Secondary Structure Transition and Critical Stress for a Model of Spider Silk Assembly. AB - Spiders spin their silk from an aqueous solution to a solid fiber in ambient conditions. However, to date, the assembly mechanism in the spider silk gland has not been satisfactorily explained. In this paper, we use molecular dynamics simulations to model Nephila clavipes MaSp1 dragline silk formation under shear flow and determine the secondary structure transitions leading to the experimentally observed fiber structures. While no experiments are performed on the silk fiber itself, insights from this polypeptide model can be transferred to the fiber scale. The novelty of this study lies in the calculation of the shear stress (300-700 MPa) required for fiber formation and identification of the amino acid residues involved in the transition. This is the first time that the shear stress has been quantified in connection with a secondary structure transition. By study of molecules containing varying numbers of contiguous MaSp1 repeats, we determine that the smallest molecule size giving rise to a "silk-like" structure contains six polyalanine repeats. Through a probability analysis of the secondary structure, we identify specific amino acids that transition from alpha-helix to beta-sheet. In addition to portions of the polyalanine section, these amino acids include glycine, leucine, and glutamine. The stability of beta-sheet structures appears to arise from a close proximity in space of helices in the initial spidroin state. Our results are in agreement with the forces exerted by spiders in the silking process and the experimentally determined global secondary structure of spidroin and pulled MaSp1 silk. Our study emphasizes the role of shear in the assembly process of silk and can guide the design of microfluidic devices that attempt to mimic the natural spinning process and predict molecular requirements for the next generation of silk-based functional materials. PMID- 26669271 TI - Strigolactone biology: genes, functional genomics, epigenetics and applications. AB - Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels. PMID- 26669272 TI - Morphology-Dependent Electrochemical Performance of Zinc Hexacyanoferrate Cathode for Zinc-Ion Battery. AB - Zinc hexacyanoferrate (ZnHCF) which is a dimorphic (cubic or rhombohedral) Prussian blue analogue and can be intercalated by both monovalent and divalent ions,is a promising cathode material for rechargeable aqueous metal-ion batteries.In this paper, a simple co-precipitation method is developed to tune the particle morphology of ZnHCF by adjusting the dropping speed at room temperature. Three polyhedral ZnHCF particles, with cubooctahedral, truncated octahedral or octahedral shapes, are obtained at room temperature. Structural transformation from cubic phase of as-prepared ZnHCF to rhombohedral phase is observed by further dehydration of the sample at 70 degrees C, whereas the dehydrated ZnHCF crystals still hold the identical polyhedral shape as that of the cubic phase particles. Then the influence of shape and facets on electrochemical performance is studied for polyhedral ZnHCF with rhombohedral structure (RZnHCF). RZnHCF sample with cubooctahedral shape possesses the best rate capability and cyclic stability comparing with RZnHCF particles having truncated octahedral or octahedral shapes. Furthermore, the structure of cuboctahedron RZnHCF particles during electrochemical cycling has been monitored with ex situ X-ray diffraction to demonstrate the reversible zinc-ion intercalation mechanism. PMID- 26669273 TI - Ovarian damage due to cyst removal: a comparison of endometriomas and dermoid cysts. AB - INTRODUCTION: Surgical treatment of endometriomas and potential damage to the ovary have been debated. Studies have described the inconsistent risk of unintended removal of ovarian tissue when a cystectomy of an endometrioma is performed. We evaluated the risk of inadvertently removed ovarian tissue during surgery by comparing specimens of endometriomas and dermoid cysts removed laparoscopically. MATERIAL AND METHODS: The material included 326 women in a retrospective cohort study at Rigshospitalet, University hospital in Copenhagen, Denmark from 2011 to 2013. Surgery was performed laparoscopically for 393 benign cysts with a diagnosis of either endometrioma (n = 294) or dermoid cyst (n = 99). The microscopic existence of ovarian tissue in the cystectomy specimens were compared and correlation between CA 125 and size of cysts was examined. RESULTS: In total, 80.3% endometrioma cystectomies disclosed ovarian stroma compared with 17.2% of the resected dermoid cysts (p < 0.001). The difference was found despite skilled laparoscopic surgeons performing the procedure in the endometriosis cohort. A significant positive correlation between the size of endometriomas and the value of CA 125 was found (p < 0.009). CONCLUSION: The risk of removal of ovarian tissue during laparoscopic surgery is significantly higher for endometriomas than for dermoid cysts. PMID- 26669275 TI - Scleral contact lenses in the management of pellucid marginal degeneration. AB - PURPOSE: To assess visual improvement with scleral lenses (PROSE, prosthetic replacement of the ocular surface ecosystem, Boston Foundation for Sightight, USA) in patients with Pellucid marginal degeneration (PMD). METHODS: This is a single-center, retrospective case-series involving patients with clinical PMD who underwent scleral lens-PROSE trial for improvement of visual acuity, from January 2009 to December 2012 at a tertiary center in India. Scleral lenses with different front surface eccentricities (FSE) were tried for improvement of visual acuity. Snellen visual acuity before and with PROSE wear was noted. Complications with PROSE wear to follow-up were noted. RESULTS: PROSE was dispensed to 12 patients (20 eyes) out of 19 patients having PMD. Location of PMD was inferior in fourteen and superior in two eyes. Four eyes had co-existing keratoconus. Nine were males and three were females. The indications for scleral lens were lens popping-out, failure of piggy-back contact lens and RGP failure. LogMAR Visual acuity improved significantly from 0.45+/-0.31 pre-PROSE to 0.05+/-0.08 post PROSE (p=0.0001). The FSE ordered was 0.6 in 17 eyes, 0.3 in one eye and 0.8 in two eyes. Three patients had hydrops over follow-up; two patients underwent keratoplasty and one was managed conservatively with steroids and hyperosmotic agents. Seven patients did not order PROSE: reasons were - no perceived improvement in visual acuity (n=2), wanted to decide (n=2), continued glasses (n=1) and continued RGP contact lens (n=1). One patient had difficulty with self lens insertion. CONCLUSION: PROSE improves visual acuity in PMD; three patients developed hydrops over follow-up. PMID- 26669274 TI - Mechanotransduction of Neural Cells Through Cell-Substrate Interactions. AB - Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell-substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell-material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell-substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo. PMID- 26669276 TI - Epigenetic targets for the treatment of neurodegenerative diseases. PMID- 26669277 TI - Role of levosimendan in the management of subarachnoid hemorrhage. AB - Aneurysmal subarachnoid hemorrhage (aSAH) is one of the leading causes of neurologic disability accounting for dismal long term survival rates. aSAH leads to a sudden increase in intracranial pressure and a massive sympathetic discharge. Excessive sympathetic stimulation leads to catecholamine mediated myocardial dysfunction and hemodynamic instability which may critically hamper brain perfusion and oxygenation. In the setting of acute aSAH, administration of vasoactive drugs aims at stabilizing impaired hemodynamics. However, studies have shown that conventional treatment with vasoactive drugs that lead to Ca(+2) overload and increase myocardial oxygen consumption, fail to restore hemodynamics and decrease cerebral blood flow. Levosimendan is a non-adrenergic inotropic Ca(+2) sensitizer with not only beneficial hemodynamic properties but also pleiotropic effects, contributing to its cardioprotective and neuroprotective role. Although there have been limited data available regarding the use of levosimendan in patients with aSAH, current evidence suggests that levosimendan may have a role in the setting of post-aSAH cardiomyopathy and decreased cerebral blood flow both in the emergency departments and in intensive care units. The purpose of this review is to provide an overview of studies of levosimendan therapy for aSAH, and describe current knowledge about the effects of levosimendan in the management of aSAH. PMID- 26669278 TI - Corrigendum: ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo. PMID- 26669279 TI - Cold-spray coating of hydroxyapatite on a three-dimensional polyetheretherketone implant and its biocompatibility evaluated by in vitro and in vivo minipig model. AB - PEEK is a bioinert material that does not chemically bind to native bone tissue and thus formation of natural bone-like hydroxyapatite (HA) coating layer on PEEK has been an important challenge to improve biocompatibility and to preserve mechanical property of PEEK. Among various coating techniques, cold-spray coating method is suitable to form stable HA coating layer on PEEK while maintaining their chemical properties, because it can be conducted in relatively low temperature range. Therefore, in this research, we used cold-spray coating method to form a thick layer of HA on the topographically complex PEEK substrates with periodic ridges on the surface and implanted in iliac bone defects of minipigs which is known to be similar with human body system. In addition, PEEK cage for clinical usage was coated with HA and inserted in the lumbar intervertebral disc space of minipig. We observed higher ALP activity, calcium production, and BSP production of human bone marrow mesenchymal stem cells on the HA-coated PEEK implants than the bare PEEK group in in vitro test. In addition, two-dimensional histological analysis and three-dimensional micro CT analysis demonstrated that implantation of complex shape of HA-PEEK hybrid implant in in vivo minipig model resulted sufficient biocompatibility and osseointegration for further clinical applications. Notably, due to the enhanced stability of PEEK cage induced from HA coating layer, osseointegration rate of the small HA blocks loaded inside the PEEK cage was also significantly improved which indicates overall increased fusion rate and adherence of the HA-coated PEEK cage. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 647-657, 2017. PMID- 26669281 TI - Sequence-based methods for detecting and evaluating the human gut mycobiome. AB - We surveyed the fungal microbiota in 16 faecal samples from healthy humans with a vegetarian diet. Fungi were identified using molecular cloning, 454 pyrosequencing and a Luminex analyte-specific reagent (ASR) assay, all targeting the ITS region of the rRNA genes. Fungi were detected in each faecal sample and at least 46 distinct fungal operational taxonomic units (OTUs) were detected, from two phyla - Ascomycota and Basidiomycota. Fusarium was the most abundant genus, followed by Malassezia, Penicillium, Aspergillus and Candida. Commonly detected fungi such as Aspergillus and Penicillium, as well as known dietary fungi Agaricus bisporus and Ophiocordyceps sinensis, are presumed to be transient, allochthonous members due to their abundance in the environment or dietary associations. No single method identified the full diversity of fungi in all samples; pyrosequencing detected more distinct OTUs than the other methods, but failed to detect OTUs in some samples that were detected by cloning and/or ASR assays. ASRs were limited by the commercially available assays, but the potential to design new, optimized assays, coupled with speed and cost, makes the ASR method worthy of further study. SIGNIFICANCE AND IMPACT OF THE STUDY: Fungi play a role in human gut ecology and health. The field lags immensely behind bacterial gut microbiota research, and studies continue to identify new fungi in faecal samples from healthy humans. However, many of these 'new' species are incapable of growth in the human GI tract, let alone making a meaningful contribution to the gut microbial community. Fungi actually inhabiting and impacting the gut likely constitute a small set of species, and an optimized, targeted, probe-based assay may prove to be the most sensible way of quantifying their abundances. PMID- 26669280 TI - Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had >=1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients. PMID- 26669282 TI - Persistence with mirabegron therapy for overactive bladder: A real life experience. AB - AIMS: To evaluate persistence rates of patients receiving mirabegron therapy for overactive bladder (OAB) within our institution over a 6 month period, identify determinants of early discontinuation of therapy, and assess overall patient satisfaction with treatment. METHODS: Hospital prescription data were analyzed in order to identify all patients who had been prescribed mirabegron in our institution. Case notes were retrospectively reviewed to obtain demographic data, previous treatments for OAB, reasons for discontinuation of previous treatments, and duration of treatment with mirabegron. Overall satisfaction with treatment was assessed using the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q). RESULTS: One hundred and ninety-seven patients were prescribed mirabegron. Of these, 81% previously discontinued anticholinergic therapy, 14% had previously received intravesical botulinum toxin A therapy, and 19% were prescribed mirabegron first-line. At 3 months 69% persisted with treatment which fell to 48% by 6 months. The commonest reason for discontinuation was lack of efficacy, followed by adverse effects. Overall 32% of patients preferred mirabegron over previous treatments and only 39% were satisfied with mirabegron therapy. CONCLUSION: Persistence rates with mirabegron in this group of patients for OAB are satisfactory. The commonest reasons for discontinuation are unmet treatment expectations and adverse effects. We had very few treatment-naive patients and so further studies are required to assess mirabegron persistence rates with longer term follow up, as first-line treatment and in different groups of OAB severity. Neurourol. Neurourol. Urodynam. 36:404-408, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26669284 TI - Interface Engineering in Two-Dimensional Heterostructures: Towards an Advanced Catalyst for Ullmann Couplings. AB - The design of advanced catalysts for organic reactions is of profound significance. During such processes, electrophilicity and nucleophilicity play vital roles in the activation of chemical bonds and ultimately speed up organic reactions. Herein, we demonstrate a new way to regulate the electro- and nucleophilicity of catalysts for organic transformations. Interface engineering in two-dimensional heteronanostructures triggered electron transfer across the interface. The catalyst was thus rendered more electropositive, which led to superior performance in Ullmann reactions. In the presence of the engineered 2D Cu2 S/MoS2 heteronanostructure, the coupling of iodobenzene and para-chlorophenol gave the desired product in 92 % yield under mild conditions (100 degrees C). Furthermore, the catalyst exhibited excellent stability as well as high recyclability with a yield of 89 % after five cycles. We propose that interface engineering could be widely employed for the development of new catalysts for organic reactions. PMID- 26669283 TI - Dietary carbohydrate intake, glycaemic load, glycaemic index and ovarian cancer risk in African-American women. AB - Epidemiological evidence regarding the association between carbohydrate intake, glycaemic load (GL) and glycaemic index (GI) and risk of ovarian cancer has been mixed. Little is known about their impact on ovarian cancer risk in African American women. Associations between carbohydrate quantity and quality and ovarian cancer risk were investigated among 406 cases and 609 controls using data from the African American Cancer Epidemiology Study (AACES). AACES is an ongoing population-based case-control study of ovarian cancer in African-Americans in the USA. Cases were identified through rapid case ascertainment and age- and site matched controls were identified by random-digit dialling. Dietary information over the year preceding diagnosis or the reference date was obtained using a FFQ. Multivariable logistic regression models were used to estimate odds ratios and 95% CI adjusted for covariates. The OR comparing the highest quartile of total carbohydrate intake and total sugar intake v. the lowest quartile were 1.57 (95% CI 1.08, 2.28; P trend=0.03) and 1.61 (95% CI 1.12, 2.30; P trend<0.01), respectively. A suggestion of an inverse association was found for fibre intake. Higher GL was positively associated with the risk of ovarian cancer (OR 1.18 for each 10 units/4184 kJ (1000 kcal); 95% CI 1.04, 1.33). No associations were observed for starch or GI. Our findings suggest that high intake of total sugars and GL are associated with greater risk of ovarian cancer in African-American women. PMID- 26669285 TI - Electrophysiological measurement of information flow during visual search. AB - The temporal relationship between different stages of cognitive processing is long debated. This debate is ongoing, primarily because it is often difficult to measure the time course of multiple cognitive processes simultaneously. We employed a manipulation that allowed us to isolate ERP components related to perceptual processing, working memory, and response preparation, and then examined the temporal relationship between these components while observers performed a visual search task. We found that, when response speed and accuracy were equally stressed, our index of perceptual processing ended before both the transfer of information into working memory and response preparation began. However, when we stressed speed over accuracy, response preparation began before the completion of perceptual processing or transfer of information into working memory on trials with the fastest reaction times. These findings show that individuals can control the flow of information transmission between stages, either waiting for perceptual processing to be completed before preparing a response or configuring these stages to overlap in time. PMID- 26669286 TI - Population differentiation and behavioural association of the two 'personality' genes DRD4 and SERT in dunnocks (Prunella modularis). AB - Quantifying the variation in behaviour-related genes within and between populations provides insight into how evolutionary processes shape consistent behavioural traits (i.e. personality). Deliberate introductions of non-native species offer opportunities to investigate how such genes differ between native and introduced populations and how polymorphisms in the genes are related to variation in behaviour. Here, we compared the genetic variation of the two 'personality' genes, DRD4 and SERT, between a native (United Kingdom, UK) and an introduced (New Zealand, NZ) population of dunnocks, Prunella modularis. The NZ population showed a significantly lower number of single nucleotide polymorphisms (SNPs) compared to the UK population. Standardized F'st estimates of the personality genes and neutral microsatellites indicate that selection (anthropogenic and natural) probably occurred during and post the introduction event. Notably, the largest genetic differentiation was found in the intronic regions of the genes. In the NZ population, we also examined the association between polymorphisms in DRD4 and SERT and two highly repeatable behavioural traits: flight-initiation distance and mating status (promiscuous females and cobreeding males). We found 38 significant associations (for different allele effect models) between the two behavioural traits and the studied genes. Further, 22 of the tested associations showed antagonistic allele effects for males and females. Our findings illustrate how introduction events and accompanying ecological changes could influence the genetic diversity of behaviour-related genes. PMID- 26669288 TI - Nodular Colloid Milium of the Conjunctiva and Anterior Orbit. AB - Colloid milium is a rare deposition disorder with accumulation of a characteristic amorphous substance in both protected and sun-exposed areas depending upon the disease subtype. The patient was a 59-year-old woman who was referred for evaluation of a gelatinous-appearing mass in the inferior fornix of the right eye, extending from the medial to the lateral canthal region, and extending up onto the bulbar conjunctival surface and anterior lacrimal gland. Hematoxylin and eosin stain of an incisional biopsy showed deposits of an amorphous brightly eosinophilic material within the conjunctiva with scattered plasma cells at the periphery. There was no evidence of monoclonality, and a Congo red stain was negative. Based on histopathologic findings, a diagnosis of nodular orbital colloid milium was made. To our knowledge, the adult and nodular forms of colloid milium have not been previously described as occurring in the conjunctiva or anterior orbit. PMID- 26669289 TI - Evaluation of the Microvascular Blood Flow, Oxygenation, and Survival of Tarsoconjunctival Flaps Following the Modified Hughes Procedure. AB - PURPOSE: For the modified Hughes procedure, a tarsoconjunctival flap from the upper eyelid is used to reconstruct large, full-thickness, lower eyelid defects. The conjunctival pedicle is divided once vascularization is deemed to be adequate. The importance of maintaining a flap pedicle to ensure adequate perfusion of the graft has been questioned. The purpose of the study was to investigate the microvascular blood flow, oxygenation, and survival of a tarsoconjunctival flap in an experimental porcine model of the modified Hughes procedure. METHODS: The modified Hughes procedure was performed in 9 pigs. Microvascular blood flow was measured by laser Doppler velocimetry. Tissue oxygenation was measured using a Licox system, and tissue survival was determined by analyzing histologic sections of biopsy specimens from the lower edge of the flap. RESULTS: Blood flow and the oxygenation of the tissue decreased gradually during dissection and advancement of the tarsoconjunctival flap. At the time when the flap was sutured into place, there was virtually no blood flow or oxygenation of the tissue. However, flap survival did not seem to be compromised, as shown by the absence of pyknotic cell nuclei necrosis in the biopsy specimens, 12 hours after the procedure. CONCLUSIONS: The pedicle of the tarsoconjunctival flap does not seem to contribute to the nourishment of the tarsoconjunctival flap. Nourishment may be supplied by the rich vascularization of the remaining eyelid and tear film. If this is the case, single-stage grafting of a free tarsal plate may be performed, thus avoiding the eyelid-sharing stage of the procedure, without compromising the survival of the graft. PMID- 26669290 TI - Successful Treatment of Extensive Squamous Cell Carcinoma of the Conjunctiva and Upper Eyelid Skin With Topical Therapy Alone. AB - This study reports a case of extensive periocular squamous cell carcinoma of the conjunctiva, extending into the superior fornix, over the upper eyelid margin, and involving the superficial layers of the eyelid skin up to the eyebrow, that was successfully treated solely with topical therapy. PMID- 26669291 TI - Hybrid Neurofibroma/Schwannoma of the Supraorbital Nerve: Clinicopathologic Correlation of a Rare Tumor. AB - Benign peripheral nerve sheath tumors such as schwannoma and neurofibroma have long been considered distinct entities. Recently, hybrid tumors demonstrating combined morphological features of neurofibroma and schwannoma have been described, primarily in dermal locations. Only 1 case of hybrid peripheral nerve sheath tumor of the orbit has been reported in the literature. Hybrid morphology is important to recognize because of its association with the neurofibromatoses, including schwannomatosis; however, the paucity of literature on orbital hybrid peripheral nerve sheath tumor poses a diagnostic challenge. This article describes a case of hybrid neruofibroma/schwannoma of the orbit arising from the supraorbital nerve with clinicopathologic correlation. PMID- 26669292 TI - Iodine-131 Therapy and Lacrimal Drainage System Toxicity: Nasal Localization Studies Using Whole Body Nuclear Scintigraphy and SPECT-CT. AB - PURPOSE: The objective of this study was to evaluate the influence of dose on nasal localization of radioactive iodine-131 (I-131) following therapy for differentiated thyroid carcinomas. METHODS: Retrospective evaluation of all patients who underwent post-therapy I-131 whole body scintigraphy and single photon emission computed tomography was performed. Patients were divided into 2 groups; group A were treated with 100 millicurie (mCi) and group B with >=150 mCi. Databases were reviewed for demographics, diagnosis, and administered dosage of I-131. Whole body scintigraphy images were retrieved and nasal uptake was analyzed and classified as nil to trace, low, moderate, and high uptake and corresponding single photon emission CTs were analyzed for radioactive nasal activity. RESULTS: A total of 100 patients were studied, 50 in each of the groups. The M:F ratio was 1.1:1 (27:23) in group A and 1.5:1 (30:20) in group B. The mean age was 43.12 years and 54.6 years in groups A and B, respectively. Papillary carcinoma of the thyroid was the most common type accounting for 82% (41/50) of patients in group A and 62% (31/50) in group B. Imaging studies revealed nil to trace nasal activity in 80% (40/50) in group A as compared with 56% (28/50) in group B. None of the patients in group A showed high nasal uptake, whereas 4% (2/50) in group B demonstrated such high activity. CONCLUSION: Intranasal localization of radioactive I-131 was significant in patients receiving a dose of >=150 mCi. Intranasal localization may partly explain toxicity to nasolacrimal duct and may be a risk factor for subsequent development of nasolacrimal duct obstructions. PMID- 26669293 TI - Nasoorbital Osteoma Presenting as Valsalva-Induced Orbital Emphysema. AB - An 18-year-old female athlete with a history of multiple traumatic concussions presented with complaints of recurrent bouts of right periorbital swelling that arose with Valsalva maneuvers such as nose-blowing or sneezing. The swelling resolved over hours to days. A CT scan of the sinuses revealed an osteoma originating from the right ethmoid roof involving the frontal recess and projecting into the orbit. She underwent excision of the osteoma via endoscopic transnasal and transcaruncular anterior orbitotomy approaches without complication. PMID- 26669294 TI - Pediatric Periocular Keratin Horns: A Case Series. AB - There are very few published cases of periocular keratin horns that have been reported in children. This study reports 2 pediatric cases of periocular keratin horns. The authors describe a 7-year-old male child who developed a keratin horn on the right lower eyelid and a 16-year-old female who developed a caruncular keratin horn. Both cases underwent excision biopsy, and subsequent histology confirmed that there was no evidence of malignancy. However, on the basis of the current evidence in adults and the difficulty in drawing firm conclusions from the small number of reported pediatric cases, the authors suggest that these lesions should be carefully managed due to the possibility of premalignant or malignant change at the base of the lesion. PMID- 26669295 TI - Canaliculitis With Isolation of Myroides Species. AB - Genera Myroides belongs to the family flavobacteriaceae and are a group of Gram negative bacilli which are nonmotile, nonfermentative, and oxidase positive. Myroides spp. are routinely found in the soil and water and rarely cause infections in the immunocompromised patients and are usually multidrug resistant. The authors describe the first case of chronic canaliculitis caused by Myroides spp. along with a brief review of literature. The patient responded to nonincisional canalicular curettage and topical moxifloxacin. PMID- 26669296 TI - Evolution of Disc Edema in Thyroid-Related Compressive Optic Neuropathy. PMID- 26669297 TI - Novel strategy for pedunculated colon polyps after unsuccessful conventional therapy. PMID- 26669298 TI - Hepatitis C and the sex trade. PMID- 26669301 TI - Ce(3+) /Tb(3+) non-/single-/co-doped K-Lu-F materials: synthesis, optical properties, and energy transfer. AB - Using a hydrothermal method, Ce(3+) /Tb(3+) non-/single-/co-doped K-Lu-F materials have been synthesized. The X-ray diffraction (XRD) results suggest that the Ce(3+) and/or Tb(3+) doping had great effects on the crystalline phases of the final samples. The field emission scanning electron microscopy (FE-SEM) images indicated that the samples were in hexagonal disk or polyhedron morphologies in addition to some nanoparticles, which also indicated that the doping also had great effects on the sizes and the morphologies of the samples. The energy-dispersive spectroscopy (EDS) patterns illustrated the constituents of different samples. The enhanced emissions of Tb(3+) were observed in the Ce(3+) /Tb(3+) co-doped K-Lu-F materials. The energy transfer (ET) efficiency etaT were calculated based on the fluorescence yield. The ET mechanism from Ce(3+) to Tb(3+) was confirmed to be the dipole-quadrupole interaction inferred from the theoretical analysis and the experimental data. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669300 TI - Serum endocan as a survival predictor for patients with liver cirrhosis. AB - BACKGROUND: The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood. OBJECTIVE: To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis. METHODS: A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. RESULTS: During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (>=2.0 ng/mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B/C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng/mL and 85.8% and 64.4% in patients with levels >=2.0 ng/mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002). CONCLUSION: These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis. PMID- 26669302 TI - Orthosis-Shaped Sandals Are as Efficacious as In-Shoe Orthoses and Better than Flat Sandals for Plantar Heel Pain: A Randomized Control Trial. AB - OBJECTIVE: To investigate efficacy of a contoured sandal being marketed for plantar heel pain with comparison to a flat flip-flop and contoured in-shoe insert/orthosis. METHOD: 150 volunteers aged 50 (SD: 12) years with plantar heel pain (>4 weeks) were enrolled after responding to advertisements and eligibility determined by telephone and at first visit. Participants were randomly allocated to receive commercially available contoured sandals (n = 49), flat flip-flops (n = 50) or over the counter, pre-fabricated full-length foot orthotics (n = 51). Primary outcomes were a 15-point Global Rating of Change scale (GROC: 1 = a very great deal worse, 15 = a very great deal better), 13 to 15 representing an improvement and the 20-item Lower Extremity Function Scale (LEFS) on which participants rate 20 common weight bearing activities and activities of daily living on a 5-point scale (0 = extreme difficulty, 4 = no difficulty). Secondary outcomes were worst level of heel pain in the preceding week, and the foot and ankle ability measure. Outcomes were collected blind to allocation. Analyses were done on an intention to treat basis with 12 weeks being the primary outcome time of interest. RESULTS: The contoured sandal was 68% more likely to report improvement in terms of GROC compared to flat flip-flop. On the LEFS the contoured sandal was 61% more likely than flat flip-flop to report improvement. The secondary outcomes in the main reflected the primary outcomes, and there were no differences between contoured sandal and shoe insert. CONCLUSIONS AND RELEVANCE: Physicians can have confidence in supporting a patient's decision to wear contoured sandals or in-shoe orthoses as one of the first and simple strategies to manage their heel pain. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry ACTRN12612000463875. PMID- 26669303 TI - Survival Outcomes in Renal Transplant Recipients With Renal Cell Carcinoma or Transitional Cell Carcinoma From the ANZDATA Database. AB - OBJECTIVES: Our objective was to determine the incidence and outcomes of renal cell carcinoma and transitional cell carcinoma in recipients of renal allografts. MATERIALS AND METHODS: We analyzed data from 2000 to 2012 in the Australia and New Zealand Dialysis and Transplant Registry, a binational population-based database, to identify the incidence and survival outcomes of renal transplant recipients with renal cell and transitional cell carcinoma. RESULTS: Of the 8850 renal transplants, there were 60 new diagnoses of renal cancers posttransplant, with an overall cumulative incidence of 56 per 100,000 per year. Nine tumors were detected in the allograft, and 51 tumors (85%) were detected in the native kidney of the recipient. The median time of diagnosis from transplant was 6.6 years (range, 0.1-8.9 y). There were no cancer-specific deaths from allograft tumors; however, 17 cancer-specific deaths (14 from renal cell carcinoma and 3 from transitional cell carcinoma) occurred in patients with cancer in the native kidney. The 5-year and 10-year cancer-specific survival rates for renal cell carcinoma were 71.2% (95% confidence interval (CI): 57.0-84.0) and 58.5% (95% CI: 40.5-77.9), with 5-year and 10-year rates for transitional cell carcinoma of 50% (95% CI: 15.5-94.2) and 0%. CONCLUSIONS: Renal cell carcinoma occurring in the native kidney comprised most of the tumors detected after renal transplant; however, transitional cell carcinoma occurred sooner after transplant and resulted in a lower cancer-specific survival rate. While it is important to screen those at risk of TCC prior and after renal transplant, the low incidence of TCC maybe too small to justify a benefit with routine screening, compared to RCCs. PMID- 26669304 TI - Correction: Ocular Hypotensive Effects of the ATP-Sensitive Potassium Channel Opener Cromakalim in Human and Murine Experimental Model Systems. PMID- 26669305 TI - Spatio-temporal patterns of an anthrax outbreak in white-tailed deer, Odocoileus virginanus, and associated genetic diversity of Bacillus anthracis. AB - BACKGROUND: Anthrax, a soil-borne zoonosis caused by the bacterium Bacillus anthracis, is enzootic in areas of North America with frequent outbreaks in west Texas. Despite a long history of study, pathogen transmission during natural outbreaks remains poorly understood. Here we combined case-level spatio-temporal analysis and high resolution genotyping to investigate anthrax transmission dynamics. Carcass locations from a single white-tailed deer, Odocoileus virginanus, outbreak were analyzed for spatial clustering using K-function analysis and directionality with trend surface analysis and the direction test. RESULTS: The directionalities were compared to results of high resolution genotyping. The results of the spatial clustering analyses, combined with deer movement data, suggest anthrax transmission events occur within limited spatial areas, with carcass locations occurring within the activity space of adjacent cases. The directionality of the outbreak paralleled adjacent dry river beds. Isolates from the outbreak were represented by a single genotype based on multiple locus variable number tandem repeat analysis (MLVA); four sub-genotypes were identified using single nucleotide repeat (SNR) analysis. CONCLUSIONS: Areas of high transmission agreed spatially with areas of higher SNR genetic diversity; however, SNRs did not provide clear evidence of linear transmission. Overlap of case home ranges provides spatial and temporal support for localized transmission, which may include the role of necrophagous or hematophagous flies in outbreaks in this region. These results emphasize the need for active surveillance and prompt cleanup of anthrax carcasses to control anthrax both during outbreaks and between seasons. PMID- 26669306 TI - Prevalence of pathogenic trypanosomes in anaemic cattle from trypanosomosis challenged areas of Itezhi-tezhi district in central Zambia. AB - BACKGROUND: The measure of anaemia status using packed cell volume (PCV) can be a reliable indicator of African trypanosomosis (AT) in the absence of other anaemia causing conditions. However, studies that have estimated prevalence of anaemia in cattle from AT endemic areas have rarely reported the prevalence of the disease in the anaemic cattle. Therefore we investigated the prevalence of AT in anaemic cattle at sites that had recently reported the disease in Itezhi tezhi district of central Zambia. METHODS: During a survey, blood samples were collected from 564 randomly selected cattle for anaemia determination from seven crush pens (Mutenda, Kapulwe, Banachoongo, Itumbi, Iyanda, New Ngoma and Shinampamba). At a PCV- value cut off of 26 %, all samples positive for anaemia were subjected to both parasitological examination on thick and thin blood smears and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of trypanosome DNA. Fisher's exact test and a mixed effect logistic regression analyses were used to determine and measures associations, respectively. RESULTS: Of 564 cattle screened, 58 (10.3 %; 95 % CI: 7.8-12.8 %) had anaemia. PCR-RFLP results showed that 17 (29.3 %; 95 % CI; 17.2-41.4 %) anaemic cattle were positive for pathogenic trypanosomes compared to 1 (1.7 %; 95 % CI: 0.0-5.2 %) on parasitological examination using thick smears. The infections were caused by Trypanosoma congolense and Trypanosoma vivax. Fisher's exact test showed a strong association between PCV and pathogenic trypanosome infection (P = 0.004). A mixed effect multivariate logistic regression showed that a one unit increase in PCV reduced the likelihood of detecting AT with PCR-RFLP by 24.7 % (95 % CI: 4.6-40.6 %; P = 0.019) in anaemic cattle, taking into account their age and sex, with random effects for crush pen. CONCLUSION: These results suggest that T. congolense and T. vivax could be important causes of anaemia in cattle reared in AT endemic areas of Itezhi tezhi in Central Zambia. This also suggests that even though pathogenic trypanosomal infection was strongly associated with PCV, it could only account for up to 41 % of the anaemia in cattle. Therefore further investigation to ascertain other factors responsible for anaemia in AT endemic areas of Itezhi tezhi in Central Zambia is needed. PMID- 26669307 TI - Reply to: "Comments on Kristensen et al.: Clinical value of FDG-PET/CT in suspected paraneoplastic syndromes: a retrospective analysis of 137 patients": By Betul Vatankulu, Sabire Yilmaz Aksoy, Sait Sager, Metin Halac. PMID- 26669308 TI - How to use cardiac IQ*SPECT routinely? An overview of tips and tricks from practical experience to the literature. PMID- 26669309 TI - Timing in audiovisual speech perception: A mini review and new psychophysical data. AB - Recent influential models of audiovisual speech perception suggest that visual speech aids perception by generating predictions about the identity of upcoming speech sounds. These models place stock in the assumption that visual speech leads auditory speech in time. However, it is unclear whether and to what extent temporally-leading visual speech information contributes to perception. Previous studies exploring audiovisual-speech timing have relied upon psychophysical procedures that require artificial manipulation of cross-modal alignment or stimulus duration. We introduce a classification procedure that tracks perceptually relevant visual speech information in time without requiring such manipulations. Participants were shown videos of a McGurk syllable (auditory /apa/ + visual /aka/ = perceptual /ata/) and asked to perform phoneme identification (/apa/ yes-no). The mouth region of the visual stimulus was overlaid with a dynamic transparency mask that obscured visual speech in some frames but not others randomly across trials. Variability in participants' responses (~35 % identification of /apa/ compared to ~5 % in the absence of the masker) served as the basis for classification analysis. The outcome was a high resolution spatiotemporal map of perceptually relevant visual features. We produced these maps for McGurk stimuli at different audiovisual temporal offsets (natural timing, 50-ms visual lead, and 100-ms visual lead). Briefly, temporally leading (~130 ms) visual information did influence auditory perception. Moreover, several visual features influenced perception of a single speech sound, with the relative influence of each feature depending on both its temporal relation to the auditory signal and its informational content. PMID- 26669311 TI - Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7. AB - Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype. PMID- 26669312 TI - SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer 2015. AB - Colorectal cancer (CRC) is the second leading cause of cancer dead in Spain. About half the patients will eventually develop distant metastases. However, as treatment options are expanding, prognosis has steadily improved over the last decades. Management of advanced CRC should be discussed within an experienced multidisciplinary team to select the most appropriate systemic treatment (chemotherapy and targeted agents) and to integrate surgical or ablative procedures when indicated. Disease site and extent, resectability, tumor biology and gene mutations, clinical presentation, patient preferences, and comorbidities are key factors to design a customized treatment plan. The aim of these guidelines is to provide synthetic recommendations for managing advanced CRC patients. PMID- 26669313 TI - SEOM clinical guidelines in Hereditary Breast and ovarian cancer. AB - Approximately, 7 % of all breast cancers (BC) and 11-15 % of ovarian cancers (OC) are associated with inherited predisposition, mainly related to germline mutations in high penetrance BRCA1/2 genes. Clinical criteria for genetic testing are based on personal and family history to estimate a minimum 10 % detection rate. Selection criteria are evolving according to new advances in this field and the clinical utility of genetic testing. Multiplex panel testing carries its own challenges and we recommend inclusion of genes with clinical utility. We recommend screening with annual mammography from age 30 and breast MRI from age 25 for BRCA1 and BRCA2 mutation carriers. Bilateral salpingo-oophorectomy should be offered to women with a BRCA1 or BRCA2 mutation, between 35 and 40 years and after completion of childbearing, or individualise based on the earliest age of ovarian cancer diagnosed in the family. Bilateral risk-reducing mastectomy is an option for healthy BRCA1 and BRCA2 mutation carriers, as well as contralateral mastectomy for young patients with a prior BC diagnosis. BRCA genetic testing in patients with BC and OC may influence their locoregional and systemic treatment. PMID- 26669310 TI - Mibefradil represents a new class of benzimidazole TRPM7 channel agonists. AB - Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a bi-functional protein comprising an ion channel moiety covalently linked to a protein kinase domain. Currently, the prevailing view is that a decrease in the cytosolic Mg(2+) concentration leads to activation of divalent cation-selective TRPM7 currents. TRPM7 plays a role in immune responses, hypotension, tissue fibrosis, and tumor progression and, therefore, represents a new promising therapeutic target. Because of the dearth of pharmacological tools, our mechanistic understanding of the role of TRPM7 in physiology and pathophysiology still lags behind. Therefore, we have recently carried out a high throughput screen for small-molecule activators of TRPM7. We have characterized the phenanthrene naltriben as a first stimulatory agonist of the TRPM7 channel. Surprisingly, the effect of naltriben on TRPM7 was found to be unaffected by the physiological levels of cytosolic Mg(2+). Here, we demonstrate that mibefradil and NNC 50-0396, two benzimidazole relatives of the TRPM7 inhibitor NS8593, are positive modulators of TRPM7. Using Ca(2+) imaging and the patch-clamp technique, we show that mibefradil activates TRPM7-mediated Ca(2+) entry and whole-cell currents. The response to mibefradil was fast, reversible, and reproducible. In contrast to naltriben, mibefradil efficiently activates TRPM7 currents only at physiological intracellular Mg(2+) concentrations, and its stimulatory effect was fully abrogated by high internal Mg(2+) levels. Consequently, a TRPM7 variant harboring a gain-of-function mutation was insensitive to further mibefradil activation. Finally, we observed that the effect of mibefradil was selective for TRPM7 when various TRP channels were tested. Taken together, mibefradil acts as a Mg(2+)-regulated agonist of the TRPM7 channel and, hence, uncovers a new class of TRPM7 agonists. PMID- 26669314 TI - SEOM guidelines for the management of Malignant Melanoma 2015. AB - All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams. PMID- 26669315 TI - Influence of Varying Assessment Parameters on the Diagnostic Accuracy of Magnetic Resonance Imaging in the Local Staging of Prostate Cancer. AB - INTRODUCTION: There is a broad variability in the accuracy levels of MRI with regard to the local staging of prostate cancer (PCa). METHODS: A prospective analysis was conducted in patients with localized PCa with MRI of the prostate before radical prostatectomy. MRI and pathology findings were independently reviewed and reported based on a standardized map of the prostate with 16 regions of interest (ROIs). Diagnostic accuracy analysis of the MRI was performed using varying prostate-subpart sizes and varying cutoffs for the radiological probability for PCa presence. RESULTS: Seventy four patients were included. Using varying cutoff probabilities and varying sizes of prostate-subparts resulted in a broad range of sensitivity (6-88%) and specificity (38-100%). Lower probabilities of PCa presence and larger prostate-subparts resulted in higher sensitivity but lower specificity and vice versa. Best diagnostic performance was achieved by using prostate sextants and at least moderate probabilities for PCa presence; mean sensitivity and specificity were 38% (95% CI 13-75) and 95% (95% CI 88-98). CONCLUSION: The use of varying assessment parameters strongly affects the diagnostic accuracy of MRI in the local staging of PCa. Hence, precise and standardized reporting regarding these parameters is important. In our study, using at least moderate probabilities for PCa presence on MRI and prostatic sextants as ROI size was associated with best diagnostic performance. PMID- 26669316 TI - [Treatment safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation]. AB - Non-vitamin K oral anticoagulants (NOAC) have now become established for stroke prevention in atrial fibrillation. The efficacy is at least as good if not better than that of vitamin K antagonists (VKA). The risk for major bleeding is less for NOAC than for VKA, with a particular superiority concerning the avoidance of intracerebral hemorrhage. The outcome after major bleeding is more favorable in patients receiving NOAC compared to those treated with VKA. Specific reversal agents for NOAC are currently being tested which neutralize the effects of NOAC within minutes and the clinical introduction of the first one for the thrombin inhibitor dabigatran is imminent. Such specific antidotes will further improve the safety profile of NAOC. PMID- 26669318 TI - Erratum to: Drought tolerance and proteomics studies of transgenic wheat containing the maize C4 phosphoenolpyruvate carboxylase (PEPC) gene. PMID- 26669317 TI - The association between social network factors and mental health at different life stages. AB - OBJECTIVES: Psychosocial factors are important determinants of an individual's health. This study examines the association between health scores and social network factors on mental health across different life stages. METHODS: Data were drawn from the Household Income and Labour Dynamics in Australia survey for adolescents (n = 1739), adults (n = 10,309) and seniors (n = 2287). Hierarchical regression modelling was applied to examine effects within and across age groups. All the variables were derived from the self-completion questionnaire. RESULTS: The social network factors were statistically significant predictors of mental health outcomes for all three life stages. For adolescents, the three social network factors were statistically significant with social isolation having the largest impact (beta = -.284, p < .001), followed by social connection (beta = .084, p < .001) and social trust having a similar effect (beta = .073, p < .001). For adults social isolation had the highest impact (beta = -.203, p < .001), followed by social connection (beta = .110, p < .001) and social trust (beta = .087, p < .001).The results for seniors were social isolation (beta = -.188, p < .001), social connection (beta = .147, p < .001) and social trust (beta = .032, p < .05). CONCLUSIONS: After adding the social network factors, the models improved significantly with social isolation playing the most significant role across all life stages, whereas the other social network factors played a differentiated role depending upon the life stage. These findings have practical implications in the design of mental health interventions across different life stages. PMID- 26669319 TI - Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress. AB - One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future. PMID- 26669320 TI - Symbiotic functioning, structural adaptation, and subcellular organization of root nodules from Psoralea pinnata (L.) plants grown naturally under wetland and upland conditions in the Cape Fynbos of South Africa. AB - In the Cape Fynbos of South Africa, Psoralea pinnata (L.) plants occur naturally in both wetland and well-drained soils and yet effectively fix N2 under the two contrasting conditions. In this study, nodule structure and functioning in P. pinnata plants from the two habitats were evaluated using light and transmission electron microscopy (TEM), as well as the 15N natural abundance technique. The results showed that, structurally, fully developed P. pinnata nodules were spherical in shape with six components (namely, lenticels, periderm, outer cortex, middle cortex, inner cortex, and a central bacteria-infected medulla region). Morphometric analysis revealed 44 and 84 % increase in cell area and volume of wetland nodules compared to those from upland. The percentage area of nodules occupied by the middle cortex in wetland nodules was twice that of upland nodules. As a result, the size of the medulla region in wetland nodules was significantly reduced compared to upland nodules. Additionally, the average area of medulla occupied by intercellular air spaces in wetland nodules was about five times that of upland nodules (about 431 % increase in wetland over upland nodules). TEM data also showed more bacteroids in symbiosomes of upland nodules when compared to wetland nodules. However, isotopic analysis of above-ground plant parts revealed no differences in symbiotic parameters such as N concentration, ?15N and %Ndfa between wetland and upland P. pinnata plants. These results suggest that, under limiting O2 conditions especially in wetlands, nodules make structural and functional adjustments to meet the O2 demands of N2 fixing bacteroids. PMID- 26669321 TI - Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort. AB - OBJECTIVES: Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women. STUDY DESIGN: We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13 55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables. RESULTS: Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54 0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03). CONCLUSION: Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group. PMID- 26669322 TI - The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data. AB - BACKGROUND: Lifestyle factors including cigarette smoking, alcohol consumption and nutritional habits impact on health, wellness, and the risk of chronic diseases. In the areas of in-vitro fertilization (IVF) and pregnancy, lifestyle factors influence oocyte production, fertilization rates, pregnancy and pregnancy loss, while chronic, low-grade oxidative stress may underlie poor outcomes for some IVF cases. METHODS: Here, we review the current literature and present some original, previously unpublished data, obtained from couples attending the PIVET Medical Centre in Western Australia. RESULTS: During the study, 80 % of females and 70 % of male partners completed a 1-week diary documenting their smoking, alcohol and fruit and vegetable intake. The subsequent clinical outcomes of their IVF treatment such as quantity of oocytes collected, fertilization rates, pregnancy and pregnancy loss were submitted to multiple regression analysis, in order to investigate the relationship between patients, treatment and the recorded lifestyle factors. Of significance, it was found that male smoking caused an increased risk of pregnancy loss (p = 0.029), while female smoking caused an adverse effect on ovarian reserve. Both alcohol consumption (beta = 0.074, p < 0.001) and fruit and vegetable consumption (beta = 0.034, p < 0.001) had positive effects on fertilization. CONCLUSION: Based on our results and the current literature, there is an important impact of lifestyle factors on IVF clinical outcomes. Currently, there are conflicting results regarding other lifestyle factors such as nutritional habits and alcohol consumption, but it is apparent that chronic oxidative stress induced by lifestyle factors and poor nutritional habits associate with a lower rate of IVF success. PMID- 26669324 TI - The effectiveness of buprenorphine for treating cancer pain: an abridged Cochrane review. AB - OBJECTIVES: To assess the effectiveness and tolerability of buprenorphine for cancer pain in adults and children. METHODS: We searched CENTRAL, MEDLINE, EMBASE, ISI Web of Science, ISI BIOSIS, ClinicalTrials.gov, metaRegister of Controlled Trials, WHO International Clinical Trials Registry Platform and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain to early 2015. RESULTS: We included 19 randomised controlled trials comparing buprenorphine with placebo, buprenorphine or another active drug for cancer pain. The trials included 1421 patients and examined 16 different intervention comparisons. Of the 11 studies that compared buprenorphine to another drug, 5, 3 and 3 studies, respectively, found that buprenorphine was superior, no different or inferior to the alternative treatment in side effects profile or patient preference/acceptability. Pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository, although intramuscular treatment was associated with more adverse events (1 study). One study found faster onset of pain relief after sublingual than subdermal buprenorphine, with similar analgesia duration and adverse event rates. 2 studies found transdermal buprenorphine superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine. No clear dose-response relationship was found for transdermal buprenorphine. The quality of this evidence base was limited by under-reporting, small sample sizes and attrition. CONCLUSIONS: Buprenorphine might be considered as a fourth-line option compared with the more standard therapies of morphine, oxycodone and fentanyl, and even then it would only be suitable for some patients. PMID- 26669325 TI - Correspondence regarding: Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome by Bhatt et al. PMID- 26669323 TI - Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury. AB - BACKGROUND: New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. METHODS: This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. RESULTS: Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. CONCLUSIONS: In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease. PMID- 26669326 TI - High-Efficiency Flexible Solar Cells Based on Organometal Halide Perovskites. AB - Flexible and light-weight solar cells are important because they not only supply power to wearable and portable devices, but also reduce the transportation and installation cost of solar panels. High-efficiency organometal halide perovskite solar cells can be fabricated by a low-temperature solution process, and hence are promising for flexible-solar-cell applications. Here, the development of perovskite solar cells is briefly discussed, followed by the merits of organometal halide perovskites as promising candidates as high-efficiency, flexible, and light-weight photovoltaic materials. Afterward, recent developments of flexible solar cells based on perovskites are reviewed. PMID- 26669327 TI - Transfer Charge and Energy of Ag@CdSe QDs-rGO Core-Shell Plasmonic Photocatalyst for Enhanced Visible Light Photocatalytic Activity. AB - Plasmonic heteronanostructures in semiconductor type display extraordinary photocatalytic efficiency induced by the plasmonic energy that operates in the Ag@CdSe-rGO hybrid ternary composites. The obtained plasmonic photocatalysts in nanoscale were fabricated by using a one-step hydrothermal method, during which the in situ nucleation of Ag@CdSe core-shell nanoparticles and the reduction of GO to rGO occurred simultaneously. Three different roles of Ag core and the junction of synergistic properties arising from the introduced rGO jointly enhanced the optical properties of CdSe. Localized plasmon resonance (LPR) effects of plasmonic Ag contribute to the separation of photogenerated e(-)/h(+) pairs via the electrons and resonant energy transfer. Electrochemical investigations have further confirmed the enhanced separation of the photogenerated e(-)/h(+) pairs. From comparative photocatalytic experiments of Ag@CdSe-rGO and Ag/CdSe-rGO, the plasmonic effect of the Ag core in the Ag@CdSe rGO nanostructure serves to prolong the charge separation under visible light beyond common attached trimers. PMID- 26669328 TI - Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper. AB - An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs. PMID- 26669330 TI - It's never too early to start! PMID- 26669329 TI - Human UDP-Glucuronosyltransferase (UGT) 2B10: Validation of Cotinine as a Selective Probe Substrate, Inhibition by UGT Enzyme-Selective Inhibitors and Antidepressant and Antipsychotic Drugs, and Structural Determinants of Enzyme Inhibition. AB - Although there is evidence for an important role of UGT2B10 in the N glucuronidation of drugs and other xenobiotics, the inhibitor selectivity of this enzyme is poorly understood. This study sought primarily to characterize the inhibition selectivity of UGT2B10 by UDP-glucuronosyltransferase (UGT) enzyme selective inhibitors used for reaction phenotyping, and 34 antidepressant and antipsychotic drugs that contain an amine functional group. Initial studies demonstrated that cotinine is a highly selective substrate of human liver microsomal UGT2B10. The kinetics of cotinine N-glucuronidation by recombinant UGT and human liver microsomes (+/- bovine serum albumin) were consistent with the involvement of a single enzyme. Of the UGT enzyme-selective inhibitors employed for reaction phenotyping, only the UGT2B4/7 inhibitor fluconazole reduced recombinant UGT2B10 activity to an appreciable extent. The majority of antidepressant and antipsychotic drugs screened for effects on UGT2B10 inhibited enzyme activity with IC50 values <100 uM. The most potent inhibition was observed with the tricyclic antidepressants amitriptyline and doxepin and the tetracyclic antidepressant mianserin, and the structurally related compounds desloratadine and loratadine. Molecular modeling using a ligand-based approach indicated that hydrophobic and charge interactions are involved in inhibitor binding, whereas spatial features influence the potency of UGT2B10 inhibition. Respective mean Ki,u (+/- S.D.) values for amitriptyline, doxepin, and mianserin inhibition of human liver microsomal UGT2B10 were 0.61 +/- 0.05, 0.95 +/- 0.18, and 0.43 +/- 0.01 uM. In vitro-in vivo extrapolation indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. PMID- 26669331 TI - A cross-sectional study to compare intraocular pressure measurement by sequential use of Goldman applanation tonometry, dynamic contour tonometry, ocular response analyzer, and Corvis ST. AB - OBJECTIVE: To study the correlation and effect of sequential measurement of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST. SETTING AND DESIGN: Observational cross-sectional series from the comprehensive clinic of a tertiary eye care center seen during December 2012. METHODS: One hundred and twenty-five study eyes of 125 patients with normal IOP and biomechanical properties underwent IOP measurement on GAT, DCT, ORA, and Corvis ST; in four different sequences. Patients with high refractive errors, recent surgeries, glaucoma, and corneal disorders were excluded so as to rule out patients with evident altered corneal biomechanics. STATISTICAL ANALYSIS: Linear regression and Bland-Altman using MedCalc software. RESULTS: Multivariate analysis of variance with repeated measures showed no influence of sequence of device use on IOP (P = 0.85). Linear regression r2 between GAT and Corvis ST, Corvis ST and Goldmann correlated IOP (IOPg), and DCT and Corvis ST were 0.37 (P = 0.675), 0.63 (P = 0.607), and 0.19 (P = 0.708), respectively. The Bland-Altman agreement of Corvis ST with GAT, corneal compensated IOP, and IOPg was 2 mmHg (-5.0 to + 10.3), -0.5 mmHg (-8.1 to 7.1), and 0.5 mmHg (-6.2 to 7.1), respectively. Intraclass correlation coefficient for repeatability ranged from 0.81 to 0.96. CONCLUSIONS: Correlation between Corvis ST and ORA was found to be good and not so with GAT. However, agreement between the devices was statistically insignificant, and no influence of sequence was observed. PMID- 26669332 TI - Learning curves for strabismus surgery in two ophthalmologists. AB - PURPOSE: To identify the average turning point by comparing the learning curves of two surgeons learning to perform strabismus surgery. MATERIALS AND METHODS: Patients who underwent procedures to correct exotropia between January 2010 and December 2014 followed for at least 3 months were retrospectively assessed. The first 70 patients on whom each of two ophthalmologists (A and B) performed surgery to treat strabismus were divided into 7 cohorts comprising 10 patients each based on the chronological order of the surgery. Factors, including patient age, preoperative angle of deviation, operative time, and success or failure of the operation, were compared between the two surgeons. Learning curves were calculated based on changes in operative time and operation success rate. Operation success was determined by measuring the angle of deviation at a distance of 5 m 3 months after the operation. RESULTS: A turning point was observed after 40 cases for Surgeon A and 50 cases for Surgeon B based on the operative time learning curve. No turning point was observed in the operation success rate learning curve based on the absence of a specific trend. Success rate by cohort was not significantly different between the two surgeons (P > 0.05). Surgeon B had a significantly longer mean operative time than Surgeon A (P = 0.045). CONCLUSIONS: Approximately 50 cases are required for an ophthalmologist to reach a turning point in strabismus surgery. This outcome can be used as a guideline when training surgeons to perform strabismus surgery. PMID- 26669333 TI - Epidemiology and clinical characteristics of patients with glaucoma: An analysis of hospital data between 2003 and 2012. AB - PURPOSE: To assess demographic and clinical characteristics of glaucoma patients in an Ophthalmologic Hospital of Jinan, China from 2003 to 2012. MATERIALS AND METHODS: Medical charts of patients with primary open-angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were reviewed. The main outcome measures of patients with glaucoma included basic demographic data (age at presentation, gender, and residence), clinical characteristics (admission date, intraocular pressure, and naked vision), and previous history (injury, cardiovascular disease, diabetes mellitus, hypertension, smoking, and alcohol consumption). RESULTS: Data from 1458 glaucoma patients were reviewed, of which PACG and SG patients accounted for 45.40% and 47.19%, respectively. The average age of all patients with glaucoma increased from 56.05 years in 2003 to 57.83 years in 2012, and the proportion of patients from rural areas rose from 46.43% to 59.13% during 10-year period. Female gender, cardiovascular disease, and hypertension were associated with PACG. POAG was related to smoking and alcohol consumption. There was positive correlation between SG and history of injury and diabetes mellitus. CONCLUSION: PACG and SG are the major types of glaucoma. Gender, injury, diabetes mellitus, cardiovascular disease, hypertension, smoking, and alcohol consumption were associated with different types of glaucoma. PMID- 26669335 TI - Diagnostic accuracy of posterior pole asymmetry analysis parameters of spectralis optical coherence tomography in detecting early unilateral glaucoma. AB - PURPOSE: To report the diagnostic ability of posterior pole asymmetry analysis (PPAA) parameters of spectralis optical coherence tomography (OCT) in detecting early unilateral glaucoma. METHODS: A prospective, cross-sectional study which included 80 eyes of 80 normal subjects and 76 eyes of 76 patients with unilateral early primary open-angle glaucoma by Hodapp-Anderson-Parrish classification. All subjects were of age more than 18 years, best-corrected visual acuity 20/40 or better, and a refractive error within +/- 5 diopter (D) sphere and +/- 3 D cylinder. Control subjects had a normal ocular examination, intraocular pressure (IOP) <22 mmHg, no past history of high IOP, no family history of glaucoma, normal optic disc morphology, and visual field in both eyes. One eye of the control subject was randomly included. All eyes underwent OCT for retinal nerve fiber layer (RNFL) analysis and PPAA. The number of continuous black squares was noted in the asymmetry analysis (right-left + hemisphere asymmetry). The area under curve (AUC) was calculated for all OCT parameters. RESULTS: The best value for AUC for RNFL analysis was 0.858 for the inferotemporal quadrant thickness. This was similar to the best value for AUC for PPAA which was 0.833 for the inferior macular thickness parameter (P = 0.5). The AUC for the right-left and the hemisphere asymmetry part of PPAA was 0.427 and 0.499, respectively. CONCLUSION: The macular thickness PPAA parameters were equally good as the RNFL parameters. However, the asymmetry analysis parameters performed poorly and need further refinement before its use in early unilateral glaucoma diagnosis. PMID- 26669336 TI - Spectrum of ocular firework injuries in children: A 5-year retrospective study during a festive season in Southern India. AB - PURPOSE: Ocular trauma is a major cause of acquired monocular blindness in children. Firework injuries account for 20% of ocular trauma. The purpose of our study was to document the profile of ocular firework injuries in children during the festive season of Diwali and to determine the prevalence of unilateral blindness in them. MATERIALS AND METHODS: A retrospective chart analysis of ocular firework injury in children during the festival of Diwali from 2009 to 2013, conducted in a tertiary care eye center in Tamil Nadu, Southern India. Children below 18 years of age with ocular firework injuries who presented to the emergency department for 3 consecutive days - the day of Diwali, 1 day before, and 1 day after Diwali - were included in this study. RESULTS: Eighty-four children presented with firework-related ocular injuries during the study period. Male to female ratio was 4:1 with mean age 9.48 +/- 4 years. Forty-four percentage required hospitalization. The prevalence of unilateral blindness in children due to fireworks was found to be 8% (95% confidence interval - 2-13%). CONCLUSION: Vision 2020 gives high priority to avoidable blindness, especially in children. In our study, for every 12 children who presented with firecracker injury, one resulted in unilateral blindness. This is an avoidable cause of blindness. Awareness needs to be created, and changes in policy regarding sales and handling of firecrackers including mandatory use of protective eyewear should be considered. PMID- 26669334 TI - Intravitreal aflibercept treatment in eyes with exudative age-related macular degeneration following prior treatment with intravitreal ranibizumab. AB - BACKGROUND: To investigate visual and anatomical outcomes in eyes with exudative age-related macular degeneration treated with intravitreal aflibercept following prior treatment with intravitreal ranibizumab. MATERIALS AND METHODS: Retrospective, single-center study of 192 eyes treated with 0.5 mg intravitreal ranibizumab every 4 weeks for three consecutive doses followed by a variable dose schedule. After more than 12 months of ranibizumab treatment, eyes that required ranibizumab injections at 4-week or 6-week intervals were switched to aflibercept therapy. RESULTS: After 12-69 months (42 months +/- 18 months, mean +/- standard deviation [SD]) of treatment with intravitreal ranibizumab, 80 eyes were changed to 2 mg intravitreal aflibercept treatment with follow-up after 12-18 months (16 months +/- 1 month, mean +/- SD). Thirty-nine eyes had persistent macular fluid after treatment with ranibizumab. Mean logMAR visual acuity (VA) in eyes treated with ranibizumab changed by - 0.089 +/- 0.310 (mean +/- SD; P = 0.0003), which correlates to an approximate gain of 4.5 letters. The number of eyes with macular fluid decreased from 39 to 23 after aflibercept treatment. Mean logMAR VA in eyes with intraretinal macular fluid treated with aflibercept changed by -0.079 +/- 0.134 (mean +/- SD; P = 0.006), which correlates to an approximate gain of 4 letters. Mean logMAR VA in eyes with submacular fluid was not significantly different after aflibercept treatment. CONCLUSION: Eyes with persistent intraretinal macular fluid had visual and anatomic response after changing from ranibizumab to aflibercept treatment. PMID- 26669337 TI - Minimally invasive surgery for thyroid eye disease. AB - Thyroid eye disease (TED) can affect the eye in myriad ways: proptosis, strabismus, eyelid retraction, optic neuropathy, soft tissue changes around the eye and an unstable ocular surface. TED consists of two phases: active, and inactive. The active phase of TED is limited to a period of 12-18 months and is mainly managed medically with immunosuppression. The residual structural changes due to the resultant fibrosis are usually addressed with surgery, the mainstay of which is orbital decompression. These surgeries are performed during the inactive phase. The surgical rehabilitation of TED has evolved over the years: not only the surgical techniques, but also the concepts, and the surgical tools available. The indications for decompression surgery have also expanded in the recent past. This article discusses the technological and conceptual advances of minimally invasive surgery for TED that decrease complications and speed up recovery. Current surgical techniques offer predictable, consistent results with better esthetics. PMID- 26669338 TI - A case of herpes simplex keratouveitis diagnosed by real time polymerase chain reaction. PMID- 26669339 TI - A benign presentation of primary ductal adenocarcinoma of lacrimal gland: A rare malignancy. AB - A 34-year-old patient with a swelling over the upper eyelid for nearly 1 year was seen in our clinic. The history, examination and investigations were suggestive of a benign lacrimal gland tumor. The tumor and lacrimal gland were resected. Subsequent histopathological examination revealed the tumor was a primary ductal adenocarcinoma of the lacrimal gland. This is a very rare tumor with less than half a dozen cases reported so far. This case report is being presented to highlight an unusual presentation of this rare malignancy. PMID- 26669340 TI - Nondecussating retinal-fugal fiber syndrome: Clinical and neuroimaging clues to diagnosis. AB - We report the clinical details and imaging findings for a case of nondecussating retinal-fugal fiber syndrome or isolated achiasma in a 4-year-old female child. Findings included the isolated absence of optic chiasm with unremarkable rest of the optic pathway and midline structures in a child presenting clinically with see-saw nystagmus. Clinically congenital see-saw nystagmus, "mirror reversal" of visual field representation and interocular ipsilateral asymmetry on monocular visual evoked potential point toward achiasma and warrant further evaluation with magnetic resonance imaging (MRI). Isolated achiasma is a rare condition that may remain undiagnosed unless MRI is done. PMID- 26669341 TI - Unilateral acquired Brown's syndrome in systemic scleroderma: An unusual cause for diplopia. AB - Brown's syndrome can be congenital or acquired with multiple causes. It has been described as a ocular complication in various rheumatic and nonrheumatic diseases. We describe a case of 27-year-old female patient with 5 years old history of systemic scleroderma who developed vertical diplopia, a left head tilt, and restriction of left eye on elevation in adduction. The patient responded to systemic steroids with resolution of diplopia. PMID- 26669342 TI - Mobilizing slit lamp to the field: A new affordable solution. AB - We are describing a simple and affordable design to pack and carry the slit lamp to the field. Orbis staff working on the Flying Eye Hospital (FEH) developed this design to facilitate mobilization of the slit lamp to the field during various FEH programs. The solution involves using a big toolbox, a central plywood apparatus, and foam. These supplies were cut to measure and used to support the slit lamp after being fitted snuggly in the box. This design allows easy and safe mobilization of the slit lamp to remote places. It was developed with the efficient use of space in mind and it can be easily reproduced in developing countries using same or similar supplies. Mobilizing slit lamp will be of great help for staff and institutes doing regular outreach clinical work. PMID- 26669343 TI - Temporary resolution of foveal schisis following vitrectomy with silicon oil tamponade in X-linked retinoschisis with retinal detachment. AB - X-linked retinoschisis (XLR) is an uncommon bilateral vitreoretinal dystrophy characterized by typical foveoschisis in all patients that may be associated with peripheral retinoschisis. A young male with XLR with retinal detachment in his right eye underwent 23 gauge pars plana vitrectomy with silicone oil tamponade. Postoperatively, best-corrected visual acuity (BCVA) improved to 20/120 with an attached retina. Spectral-domain optical coherence tomography showed macular thinning with the collapse of the schitic cavities with silicone oil in situ. Following silicone oil removal at 6 months follow-up, the retina remained attached with a BCVA of 20/80 however the foveal schitic cavities reappeared. This unusual course has not been described previously. PMID- 26669344 TI - Traumatic central serous chorioretinopathy. PMID- 26669345 TI - Authors' response. PMID- 26669346 TI - Comment on: Bilateral angle closure glaucoma: Differential diagnosis. PMID- 26669347 TI - Comment on: Traumatic central serous chorioretinopathy. PMID- 26669348 TI - A survey of the management of vitreoretinal pathology detected prior to laser assisted in situ keratomileusis. PMID- 26669349 TI - Response to: Comparison of clinical outcomes, patient, and surgeon satisfaction following topical versus peribulbar anesthesia for phacoemulsification: A randomized controlled trial. PMID- 26669350 TI - Erratum: Effects of dexmedetomidine for retrobulbar anesthesia in orbital ball implants after enucleation surgery. PMID- 26669352 TI - [MBA - The Physician of Tomorrow?] PMID- 26669353 TI - [Spectral Reflectance Retinal Imaging: Clinical Evaluation]. PMID- 26669354 TI - [Eyelid Malpositions]. PMID- 26669355 TI - Rapid Hydrogen Shift Scrambling in Hydroperoxy-Substituted Organic Peroxy Radicals. AB - Using quantum mechanical calculations, we have investigated hydrogen shift (H shift) reactions in peroxy radicals derived from the atmospheric oxidation of 1 pentene (CH2?CHCH2CH2CH3) and its monosubstituted derivatives. We investigate the peroxy radicals, HOCH2CH(OO)CR1HCH2CH3, HOCH2CH(OO)CH2CR1HCH3, and HOCH2CH(OO)CH2CH2CR1H2, where the substituent R1 is an alcoholic (OH), a hydroperoxy (OOH), or a methoxy (OCH3) group. For peroxy radicals with an OOH substituent, the H-shift reaction from the hydrogen atom on the OOH group to the OO group is extremely fast. We find that the rate constants of this type of H shift reactions are greater than 10(3) s(-1) for both the forward and the reverse reactions. It leads to the formation of two different radical isomers that react through different reaction mechanisms and yield different products. These very fast H-shift reactions are much faster than the reactions with NO and HO2 under most atmospheric conditions and must be included in the atmospheric modeling of volatile organic compounds where hydroperoxy peroxy radicals are formed. PMID- 26669356 TI - The distribution of macronutrients, anti-nutrients and essential elements in nettles, Laportea peduncularis susp. peduncularis (River nettle) and Urtica dioica (Stinging nettle). AB - Laportea peduncularis and Urtica dioica, which are popularly known as "Nettles" belong to the plant family Urticaceae and are consumed as green vegetables or used for their medicinal benefit in many countries in Africa, Asia, Europe and America. This study aimed at investigating the effect of cooking on the macronutrient, anti-nutrient and elemental composition of L. peduncularis and U. dioica leaves. The results showed a decrease in the crude fat, ash, carbohydrate and vitamin C content with cooking, but an increase in the vitamin E content. The anti-nutrient content (cyanides, phytates and saponins) increased slightly with cooking, while the oxalate content has decreased. The concentration of essential elements in cooked L. peduncularis leaves were found to be in decreasing order of Ca > Mg > Fe > Mn > Zn > Cu > Cr > Ni > Co. Both raw and cooked leaves of nettles were found to be rich sources of macronutrients and essential elements and may be used as alternatives to commercially available nutrient supplements. Statistical analyses (principal component analysis and correlations) indicated that certain elements taken up by these plants were from common sources. Both positive and negative relationships between nutrients, anti-nutrients and elements were observed in the plant leaves. PMID- 26669361 TI - Platinum-Mediated Activation of Coordinated Organonitriles by Telluroethers in Tetrahydrofuran: Isolation, Structural Characterization, and Density Functional Theory Analysis of Intermediate Complexes. AB - The reactions of [PtCl2(NCR)2] with telluroethers (ArAr'Te) in organic solvents have been investigated. The reactions in dichloromethane yield [PtCl2(TeArAr')2], while those in tetrahydrofuran (THF) give different products depending on the steric demands of the aryl groups on tellurium, the molarity of the reactants, and the reaction conditions. The reactions between [PtCl2(PhCN)2] and TeArAr' in 1:1 molar ratio at room temperature in THF yield several products, like [PtCl2(TeArAr')2] (Ar/Ar' = Ph/Ph, o-tol/Mes, Mes/Mes), [PtCl2(PhCN){NC(O)Ph[TeMes(o-tol)]}], and [PtCl2{NC(O)Ph(TeMes2)}2]. The reaction with TeMes2 in refluxing THF gave [PtCl2{NC(Ph)C4H7O}{NC(O)Ph(TeMes2)}] and [PtCl(TeMes2){Te(Mes)CH2C6H2Me2}], depending on the duration of heating. Reaction of [PtCl2(PhCN)2] with TeArMes afforded [PtCl2(TeArMes)2] (Ar = Ph, o-tol, and Mes), the formation of which decreased with increasing steric demand of the Ar group, together with [PtCl2{NC(O)Ph(TeArMes)}2]. The telluroether in the latter binds to nitrogen, and tellurium exists in the formal oxidation state of +4 (from XPS). The tellurium in these complexes exhibits secondary interactions with platinum (J((195)Pt-(125)Te) = 309-347 Hz) and with the carbonyl oxygen. These complexes slowly dissociate in solution to give [PtCl2(TeMesAr){NC(O)Ph(TeMesAr)}], finally leading to the formation of [PtCl2(TeMesAr)2]. Molecular structures of trans-[PtCl2(PhCN){NC(O)Ph[TeMes(o tol)]}], trans-[PtCl2{NC(O)Ph(TeMes2)}2], trans [PtCl2{NC(Ph)C4H7O}{NC(O)Ph(TeMes2)}], trans-[PtCl2{NC(O)Ph[TeMes(o-tol)]}2], trans-[PtCl2(TeMes2){NC(O)Ph(TeMes2)}], trans-[PtCl2{NC(O)Me(TeMes2)}2], and [PtCl(Te-o-tol){NC(O)Ph}2] have been unambiguously established by single-crystal X-ray diffraction analyses. Density functional theory calculations for some of the complexes were performed, and geometrical parameters are in good agreement with the values obtained from X-ray analyses. PMID- 26669358 TI - Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. AB - OBJECTIVES: Open nephroureterectomy (ONU) is the current standard for muscle invasive upper tract urothelial carcinoma (UTUC) in the European Association of Urology/Japanese Urological Association (JUA) guidelines. In this study, we compared the postsurgical survival of muscle-invasive UTUC patients treated with ONU or with laparoscopic nephroureterectomy (LNU), using the multi-institutional national database of the JUA. METHODS: The 1509 patients with UTUC who were diagnosed at 348 Japanese institutions in 2005 were registered. We collected the clinical data of the patients in 2011. The muscle-invasive UTUC patients who underwent ONU or LNU were identified, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Overall, 749 pT2>=cNxM0 patients underwent a nephroureterectomy (ONU, n = 527 and LNU, n = 222). The overall survival and cause-specific survival rates were not significantly different between the ONU and LNU groups (p = 0.1263 and p = 0.0893, respectively). In addition, 459 of the 749 (61.3%) patients experienced disease recurrence (bladder recurrence, local recurrence, or distant metastasis), with no significant difference between the ONU and LNU groups. Even when patients were stratified by pT3/pT4 and/or pN+, overall survival was not significantly different between the ONU and LNU groups (p = 0.2876). The results of a univariate analysis showed that lymphovascular invasion was an independent prognostic factor for overall survival, but the surgical approaches were not found to be associated with overall survival. CONCLUSIONS: Our data suggest that there is no evidence that the oncologic outcome of LNU is inferior to that of ONU in muscle-invasive UTUC, when the appropriate patients are selected. PMID- 26669357 TI - Desmoplakin Variants Are Associated with Idiopathic Pulmonary Fibrosis. AB - RATIONALE: Sequence variation, methylation differences, and transcriptional changes in desmoplakin (DSP) have been observed in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To identify novel variants in DSP associated with IPF and to characterize the relationship of these IPF sequence variants with DSP gene expression in human lung. METHODS: A chromosome 6 locus (7,370,061-7,606,946) was sequenced in 230 subjects with IPF and 228 control subjects. Validation genotyping of disease-associated variants was conducted in 936 subjects with IPF and 936 control subjects. DSP gene expression was measured in lung tissue from 334 subjects with IPF and 201 control subjects. MEASUREMENTS AND MAIN RESULTS: We identified 23 sequence variants in the chromosome 6 locus associated with IPF. Genotyping of selected variants in our validation cohort revealed that noncoding intron 1 variant rs2744371 (odds ratio = 0.77, 95% confidence interval [CI] = 0.66-0.91, P = 0.002) is protective for IPF, and a previously described IPF-associated intron 5 variant (rs2076295) is associated with increased risk of IPF (odds ratio = 1.36, 95% CI = 1.19-1.56, P < 0.001) after controlling for sex and age. DSP expression is 2.3-fold increased (95% CI = 1.91-2.71) in IPF lung tissue (P < 0.0001). Only the minor allele at rs2076295 is associated with decreased DSP expression (P = 0.001). Staining of fibrotic and normal human lung tissue localized DSP to airway epithelia. CONCLUSIONS: Sequence variants in DSP are associated with IPF, and rs2076295 genotype is associated with differential expression of DSP in the lung. DSP expression is increased in IPF lung and concentrated in the airway epithelia, suggesting a potential role for DSP in the pathogenesis of IPF. PMID- 26669362 TI - A resolution for 2016 that is easy to keep. PMID- 26669363 TI - Colleagues dress to impress for Christmas--and to raise money. PMID- 26669364 TI - New guidance on end of life care centres on individualised plans. PMID- 26669365 TI - Council budget cuts could threaten health visiting. PMID- 26669366 TI - Further pressure on government over bursary plans. PMID- 26669367 TI - Scottish survey exposes low staffing levels and fears about speaking out. PMID- 26669369 TI - Cumbrian nurses to receive QNI bailout. PMID- 26669368 TI - NHS investigations into avoidable deaths 'not consistent or reliable'. PMID- 26669371 TI - Good practice to help prevent language barriers. PMID- 26669372 TI - Staring eyes prompt people to wash hands. PMID- 26669373 TI - Eager Pebbles is all ears on busy pre-admission unit. PMID- 26669374 TI - Better training needed to spot declining maternal mental health. PMID- 26669375 TI - Pay restraint, bursaries and plans for a 7-day NHS make for a turbulent year. PMID- 26669382 TI - Improving cognitive function. PMID- 26669383 TI - Singing from the same song sheet. PMID- 26669384 TI - Reaping rewards of a standard approach. PMID- 26669385 TI - Rallying support for an unpaid army. PMID- 26669395 TI - Yellow Card app. PMID- 26669398 TI - You don't know what you've got till it's gone; health visiting is in peril. PMID- 26669399 TI - Questioning overseas nurses' language skills is not helpful. PMID- 26669400 TI - Endlessly stating the obvious is affecting my sense of humour. PMID- 26669401 TI - Prepare to admire the Mary Seacole statue in the new year. PMID- 26669402 TI - Tuition fees are a gamble with the future workforce. PMID- 26669405 TI - How to remove a non-tunnelled central venous catheter. PMID- 26669406 TI - Transferring young people with cystic fibrosis to adult care. AB - AIM: To explore activities, interactions and behaviours during the first appointment in adult care for young people with cystic fibrosis. METHOD: Observational data were collected at 12 first appointments. Framework analysis was applied to written field notes. FINDINGS: Interaction enablers and interaction barriers were identified in the data. Practitioners endeavoured to be holistic, addressing personal as well as physical factors. This involved broaching individuals' interests, self-disclosure and humour. Various activities were accomplished. The role of parents in the continued management of cystic fibrosis was not raised at first appointments. DISCUSSION: Practitioners require clear objectives for first appointments in adult care to ensure young people adapt to this new healthcare setting. Young people should be prepared for transfer so they can respond to and ask questions, and parents should be assisted to relinquish control of their child's condition. Conclusion A modest set of objectives for the first appointment should be set to enable young people to retain information, while introducing them to a new service. PMID- 26669407 TI - Pressure ulcer prevention in frail older people. AB - Pressure ulcers are painful and cause discomfort, have a negative effect on quality of life, and are costly to treat. The incidence and severity of preventable pressure ulcers is an important indicator of quality of care; it is essential that healthcare providers monitor prevalence and incidence rates to ensure that care strategies implemented are effective. Frail older people are at increased risk of developing pressure ulcers. This article discusses the complexities of preventing pressure ulcers in frail older people and emphasises the importance of structured educational programmes that incorporate effective clinical leadership and multidisciplinary teamwork. PMID- 26669409 TI - How to handle bullies. PMID- 26669408 TI - Nursing revalidation. PMID- 26669410 TI - A voice for patients and staff. PMID- 26669412 TI - Be clever on training shifts. PMID- 26669413 TI - Understanding Controls on Wetting at Fluorinated Polyhedral Oligomeric Silsesquioxane/Polymer Surfaces. AB - Fluorinated polyhedral oligomeric silsesquioxane (F-POSS) nanoparticles have been widely used to enhance the hydrophobicity or oleophobicity of polymer films via constructing the specific micro/nanoscale roughness. In this work, we study the oleophobicity of pure and F-POSS-decorated poly(vinylidene fluoride) (PVDF) and poly(methyl methacrylate) (PMMA) films using a dynamic density functional theory approach. The role of nanoparticle size and coverage and the chemical features of F-POSS and the polymer film in the wetting behavior of diiodomethane droplets has been integrated to the remaining ratio of surface potential to quantitatively characterize the corner effect. It is shown that, on the basis of universal force field parameters, the theoretically predicted contact angles are in general agreement with the available experimental data. PMID- 26669414 TI - Deciphering the Biosynthetic Origin of L-allo-Isoleucine. AB - The nonproteinogenic amino acid L-allo-isoleucine (L-allo-Ile) is featured in an assortment of life forms comprised of, but not limited to, bacteria, fungi, plants and mammalian systems including Homo sapiens. Despite its ubiquity and functional importance, the specific origins of this unique amino acid have eluded characterization. In this study, we describe the discovery and characterization of two enzyme pairs consisting of a pyridoxal 5'-phosphate (PLP)-linked aminotransferase and an unprecedented isomerase synergistically responsible for the biosynthesis of L-allo-Ile from L-isoleucine (L-Ile) in natural products. DsaD/DsaE from the desotamide biosynthetic pathway in Streptomyces scopuliridis SCSIO ZJ46, and MfnO/MfnH from the marformycin biosynthetic pathway in Streptomyces drozdowiczii SCSIO 10141 drive L-allo-Ile generation in each respective system. In vivo gene inactivations validated the importance of the DsaD/DsaE pair and MfnO/MfnH pair in L-allo-Ile unit biosynthesis. Inactivation of PLP-linked aminotransferases DsaD and MfnO led to significantly diminished desotamide and marformycin titers, respectively. Additionally, inactivation of the isomerase genes dsaE and mfnH completely abolished production of all L-allo Ile-containing metabolites in both biosynthetic pathways. Notably, in vitro biochemical assays revealed that DsaD/DsaE and MfnO/MfnH each catalyze a bidirectional reaction between L-allo-Ile and L-Ile. Site-directed mutagenesis experiments revealed that the enzymatic reaction involves a PLP-linked ketimine intermediate and uses an arginine residue from the C-terminus of each isomerase to epimerize the amino acid beta-position. Consequently, these data provide important new insight into the origins of L-allo-Ile in natural products with medicinal potential and illuminate new possibilities for biotool development. PMID- 26669415 TI - Plasmon-Enhanced Autofluorescence Imaging of Organelles in Label-Free Cells by Deep-Ultraviolet Excitation. AB - We demonstrate the observation of organelles in label-free cells on an aluminum thin film using deep-ultraviolet surface plasmon resonance (DUV-SPR). In particular, the Kretschmann configuration is used for the excitation of DUV-SPR. MC3T3-E1 cells are directly cultured on the aluminum thin film, and DUV-SPR leads to autofluorescence of in the label-free MC3T3-E1. We found that nucleic acid and mitochondria in these label-free MC3T3-E1 cells quite strongly emit the autofluorescence as a result of DUV-SPR. Yeast cells are also deposited on the aluminum thin film. Tryptophan and mitochondrial nicotinamide adenine dinucleotide (NADH) in the yeast cells are subsequently excited, and their autofluorescence is spectrally analyzed in the UV region. On the basis of these results, we conclude that DUV-SPR constitutes a promising technique for the acquisition of highly sensitive autofluorescence images of various organelles in the cells. PMID- 26669416 TI - Increasing HPV vaccination through policy for public health benefit. AB - Vaccines against specific types of human papillomavirus (HPV) linked to cancer and other diseases have been met with mixed acceptance globally and in the United States. Policy-level interventions have been shown to be effective in increasing public health benefit. Government policies and mandates may result in improved HPV vaccination coverage and reduced disease burden, and alternative policies that improve unhindered access to HPV vaccination may allow success as well. The purpose of this commentary is to summarize policy efforts to maximize the public health benefit of HPV vaccination. We examine selected examples of HPV vaccination policy in global contexts and in the United States. PMID- 26669417 TI - Effects of Music Therapy on the Cardiovascular and Autonomic Nervous System in Stress-Induced University Students: A Randomized Controlled Trial. AB - OBJECTIVE: Stress is caused when a particular relationship between the individual and the environment emerges. Specifically, stress occurs when an individual's abilities are challenged or when one's well-being is threatened by excessive environmental demands. The aim of this study was to measure the effects of music therapy on stress in university students. DESIGN: Randomized controlled trial. PARTICIPANTS: Sixty-four students were randomly assigned to the experimental group (n = 33) or the control group (n = 31). INTERVENTION: Music therapy. OUTCOME MEASURES: Initial measurement included cardiovascular indicators (blood pressure and pulse), autonomic nervous activity (standard deviation of the normal to-normal intervals [SDNN], normalized low frequency, normalized high frequency, low/high frequency), and subjective stress. After the first measurement, participants in both groups were exposed to a series of stressful tasks, and then a second measurement was conducted. The experimental group then listened to music for 20 minutes and the control group rested for 20 minutes. A third and final measurement was then taken. RESULTS: There were no significant differences between the two groups in the first or second measurement. However, after music therapy, the experimental group and the control group showed significant differences in all variables, including systolic blood pressure (p = .026), diastolic blood pressure (p = .037), pulse (p < .001), SDNN (p = .003), normalized low frequency (p < .001), normalized high frequency (p = .010), and subjective stress (p = .026). CONCLUSION: Classical music tends to relax the body and may stimulate the parasympathetic nervous system. These results suggest music therapy as an intervention for stress reduction. PMID- 26669418 TI - Supramolecular Architectures of Dendritic Amphiphiles in Water. AB - Dendritic molecules are an exciting research topic because of their highly branched architecture, multiple functional groups on the periphery, and very pertinent features for various applications. Self-assembling dendritic amphiphiles have produced different nanostructures with unique morphologies and properties. Since their self-assembly in water is greatly relevant for biomedical applications, researchers have been looking for a way to rationally design dendritic amphiphiles for the last few decades. We review here some recent developments from investigations on the self-assembly of dendritic amphiphiles into various nanostructures in water on the molecular level. The main content of the review is divided into sections according to the different nanostructure morphologies resulting from the dendritic amphiphiles' self-assembly. Finally, we conclude with some remarks that highlight the self-assembling features of these dendritic amphiphiles. PMID- 26669419 TI - Preoperative Factors Affecting Stereopsis after Surgical Alignment of Acquired Partially Accommodative Esotropia. AB - BACKGROUND/AIM: Despite successful ocular realignment, many strabismus patients never develop high levels of stereopsis. The purpose of this study was to determine preoperative factors that affect postoperative stereopsis in patients with acquired partially accommodative esotropia (APAET). METHODS: This was a retrospective chart review of patients who underwent successful surgery for APAET. We compared preoperative factors between patients achieving postoperative stereopsis of 100 seconds of arc or better versus those with worse than 100 seconds of arc. RESULTS: Fifty-seven patients met our inclusion criteria. Twenty four (42%) had a final stereopsis of 100 seconds of arc or better. The mean age of onset of esodeviation for patients attaining stereopsis of 100 seconds of arc or better was 31.8 +/- 12.9 months, versus 23.9 +/- 10.0 months (p = 0.012) for patients with worse than 100 seconds of arc. Duration of constant misalignment was not significantly different between the two groups (30.1 +/- 18.5 for patients attaining 100 seconds of arc versus 27.3 +/- 18.6 months; p = 0.57). A multivariate regression analysis found older age of onset to be the only predictive factor for achieving better postoperative stereopsis (odds ratio 1.065, 95% CI: 1.014-1.118). CONCLUSION: Age of onset appears to be the most important factor affecting postoperative stereopsis in patients with APAET. Patients with an age of onset after 36 months tended to have better outcomes regardless of the duration of misalignment. Duration of misalignment and age at surgery did not have a significant impact on postoperative stereopsis in our patient population. PMID- 26669420 TI - Minimally Invasive Strabismus Surgery (MISS) Compared with the Fornix Approach in Pediatric Horizontal Strabismus Surgery. AB - OBJECTIVE: To compare minimally invasive strabismus surgery (MISS) with the fornix approach in horizontal strabismus operations. PATIENTS AND METHODS: We performed a retrospective study of all patients aged <= 12 years who underwent symmetrical surgery of the medial or lateral recti over a 1-year period. MISS was performed in one eye, and fornix opening was performed in the contralateral. We compared pre- and postoperative visual acuity (VA), conjunctival hyperemia, swelling after surgery, and operating time. The techniques were performed by 2 surgeons after a 4-year training period. RESULTS: The sample comprised 16 patients, with a mean age of 6.75 +/- 3.02 years. The medial rectus was operated on in 9, the lateral rectus in 7 cases. Recession was performed in 14 muscles (mean dose, 5 mm) and plication in 2 (5.5 mm and 7 mm, respectively). MISS was performed in 12 right eyes and 4 left eyes. Preoperative VA was 0.77 in MISS and 0.80 in the control group. VA was 0.83 in MISS and 0.76 in the control group 1 day after surgery. No significant differences were found for conjunctival hyperemia between the MISS and fornix groups 1 day or 1 week after surgery. Nevertheless, moderate/severe conjunctival hyperemia was less frequent in the MISS group (31.3% versus 62.5%). No significant differences were found for operating time (14.43 minutes [MISS] vs 12.37 minutes [control]). CONCLUSION: The MISS technique was similar to the fornix approach in the early postoperative period with respect to VA, conjunctival inflammation, and operating time in pediatric horizontal strabismus surgery. PMID- 26669421 TI - Clinical Assessment of Stereoacuity and 3-D Stereoscopic Entertainment. AB - BACKGROUND/AIMS: The perception of compelling depth is often reported in individuals where no clinically measurable stereoacuity is apparent. We aim to investigate the potential cause of this finding by varying the amount of stereopsis available to the subject, and assessing their perception of depth viewing 3-D video clips and a Nintendo 3DS. METHODS: Monocular blur was used to vary interocular VA difference, consequently creating 4 levels of measurable binocular deficit from normal stereoacuity to suppression. Stereoacuity was assessed at each level using the TNO, Preschool Randot(r), Frisby, the FD2, and Distance Randot(r). Subjects also completed an object depth identification task using the Nintendo 3DS, a static 3DTV stereoacuity test, and a 3-D perception rating task of 6 video clips. RESULTS: As intraocular VA differences increased, stereoacuity of the 57 subjects (aged 16-62 years) decreased (eg, 110", 280", 340", and suppression). The ability to correctly identify depth on the Nintendo 3DS remained at 100% until suppression of one eye occurred. The perception of a compelling 3-D effect when viewing the video clips was rated high until suppression of one eye occurred, where the 3-D effect was still reported as fairly evident. CONCLUSION: If an individual has any level of measurable stereoacuity, the perception of 3-D when viewing stereoscopic entertainment is present. The presence of motion in stereoscopic video appears to provide cues to depth, where static cues are not sufficient. This suggests there is a need for a dynamic test of stereoacuity to be developed, to allow fully informed patient management decisions to be made. PMID- 26669422 TI - Progressive-Addition Lenses for Accommodative Esotropia with a High Accomodative Element. AB - PURPOSE: Accommodative esotropia with a high accommodative element has been typically treated with bifocal lenses. This study assessed the age-dependent efficacy of progressive-addition lenses (PAL) for a high accommodative element in improving motor and sensory performance. METHODS: We evaluated PAL as an initial treatment modality or after initiating treatment with bifocals at various ages. Thirty-two patients, who did not undergo eye muscle surgery, were included in this retrospective study. Subjects were divided into 2 subgroups: 7 subjects who received PAL treatment only (median age 4.5 years), and 25 children treated with bifocals (median age 4.5 years) and then switched to PAL at the mean age of 9 years. Measurement of the deviation was performed by the alternate prism cover test. The Stereo fly test and Randot stereo test were used to assess stereoacuity. The mean follow-up periods for the subgroups were 57 and 46 months, respectively. RESULTS: The deviation at near decreased in the PAL-only group from an average of 28 prism diopters (PD) without correction at diagnosis to zero PD with correction. Stereopsis in the PAL first group improved from an average of 113" to 54" and in the bifocals first group improved from 541" to 141". CONCLUSION: PAL treatment for accommodative esotropia with a high accommodative achieved good sensory and motor results. PAL and bifocals were equally beneficial as the initial treatment of young children with convergence excess esotropia. PMID- 26669423 TI - Surgery for Supranuclear Monocular Elevation Deficiency. AB - PURPOSE: We report a novel approach to surgery for monocular elevation deficiency (MED). METHODS: A retrospective review of 5 patients undergoing surgery for supranuclear MED between 2003 and 2014. All patients had intact Bell's phenomenon, hypotropia, limited elevation above the primary position, and negative forced duction testing of the paretic eye. Preoperatively all patients preferred chin-up head posture and three had pseudoptosis or ptosis. One of the 5 had prior vertical muscle surgery. Surgery correction for the MED consisted of near maximal superior rectus recession on the contralateral sound eye. RESULTS: Compensatory chin-up head position and alignment in primary position was improved in all patients. Average age at surgery was 5.3 years. Average superior rectus recession was 9.7 mm. Mean follow-up was 4.8 years (range 12 months to 11.5 years). The vertical deviation of the paretic eye in primary position postoperatively was orthotropic for 2, hypotropic for 2, and overcorrected for 1. CONCLUSIONS: In cases of supranuclear MED (double elevator palsy) contralateral superior rectus recession based on the innervational principle is a simple and reliable alternative surgical approach compared to published results of the Knapp transposition procedure. Additionally, it holds the possibility for decreased complications and less complicated future surgical treatment options. PMID- 26669424 TI - Early American Strabismus Surgery: 1840-1845. AB - The discovery of effective surgical therapy for strabismus was one of the outstanding triumphs of the first half of 19th-century ophthalmology, just prior to the invention of the ophthalmoscope in 1850. Although priority for the development of strabismus surgery belongs to Johann Friedrich Dieffenbach of Germany, who first reported his surgical results in 1839, 4 cases of tenotomy of the medial rectus muscle had been performed in the United States by William Gibson in 1818 but never published. By 1840, the reports of surgery in Europe had rapidly spread to America where surgeons immediately began using these procedures. The first American surgeon to perform eye muscle surgery and publish his results was John Dix of Boston, and other surgeons were soon reporting their cases as well. We discuss 8 American pioneers in this field during the time (1840 1845) of the first burst of enthusiasm for this surgery. Although these surgeons were active in performing a large number of cases and carefully reporting their experiences and results, they did not make any major advances in the field. PMID- 26669425 TI - Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice. AB - B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)-GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligand-receptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3-3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,beta-cyclohexyl-Ala8,D-Tic16,Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13psi(CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNP induced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRL-elicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch. PMID- 26669426 TI - The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice. AB - Administration of biologics to enhance T-cell function is part of a rapidly growing field of cancer immunotherapy demonstrated by the unprecedented clinical success of several immunoregulatory receptor targeting antibodies. While these biologic agents confer significant anti-tumor activity through targeted immune response modulation, they can also elicit broad immune responses potentially including the production of anti-drug antibodies (ADAs). DTA-1, an agonist monoclonal antibody against GITR, is a highly effective anti-tumor treatment in preclinical models. We demonstrate that repeated dosing with murinized DTA-1 (mDTA-1) generates ADAs with corresponding reductions in drug exposure and engagement of GITR on circulating CD3(+) CD4(+) T cells, due to rapid hepatic drug uptake and catabolism. Mice implanted with tumors after induction of preexisting mDTA-1 ADA show no anti-tumor efficacy when given 3 mg/kg mDTA-1, an efficacious dose in naive mice. Nonetheless, increasing mDTA-1 treatment to 30 mg/kg in ADA-positive mice restores mDTA-1 exposure and GITR engagement on circulating CD3(+) CD4(+) T cells, thereby partially restoring anti-tumor efficacy. Formation of anti-mDTA-1 antibodies and changes in drug exposure and disposition does not occur in GITR(-/-) mice, consistent with a role for GITR agonism in humoral immunity. Finally, the administration of muDX400, a murinized monoclonal antibody against the checkpoint inhibitor PD-1, dosed alone or combined with mDTA-1 did not result in reduced muDX400 exposure, nor did it change the nature of the anti-mDTA-1 response. This indicates that anti-GITR immunogenicity may not necessarily impact the pharmacology of coadministered monoclonal antibodies, supporting combination immunomodulatory strategies. PMID- 26669427 TI - Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling. AB - Citral, eucalyptol, and linalool are widely used as flavorings, fragrances, and cosmetics. Here, we examined their effects on electrophysiological and binding properties of human 5-HT3 receptors expressed in Xenopus oocytes and human embryonic kidney 293 cells, respectively. Data were analyzed using nonlinear mixed-effects modeling to account for random variance in the peak current response between oocytes. The oils caused an insurmountable inhibition of 5-HT evoked currents (citral IC50 = 120 uM; eucalyptol = 258 uM; linalool = 141 uM) and did not compete with fluorescently labeled granisetron, suggesting a noncompetitive mechanism of action. Inhibition was not use-dependent but required a 30-second preapplication. Compound washout caused a slow (~180 seconds) but complete recovery. Coapplication of the oils with bilobalide or diltiazem indicated they did not bind at the same locations as these channel blockers. Homology modeling and ligand docking predicted binding to a transmembrane cavity at the interface of adjacent subunits. Liquid chromatography coupled to mass spectrometry showed that an essential oil extracted from Lippia alba contained 75.9% citral. This inhibited expressed 5-HT3 receptors (IC50 = 45 ug ml(-1)) and smooth muscle contractions in rat trachea (IC50 = 200 ug ml(-1)) and guinea pig ileum (IC50 = 20 ug ml(-1)), providing a possible mechanistic explanation for why this oil has been used to treat gastrointestinal and respiratory ailments. These results demonstrate that citral, eucalyptol, and linalool inhibit 5-HT3 receptors, and their binding to a conserved cavity suggests a valuable target for novel allosteric modulators. PMID- 26669429 TI - Mass production of graphene nanoscrolls and their application in high rate performance supercapacitors. AB - The output of graphene nanoscrolls (GNSs) has been greatly enhanced to the gram level by using an improved spray-freeze-drying method without damaging the high transforming efficiency (>92%). The lowest bulk density of GNS foam reaches 0.10 mg cm(-3). Due to the unique morphology and high specific surface area (386.4 m(2) g(-1)), the specific capacitances of the GNSs (90-100 F g(-1) at 1 A g(-1)) are all superior to those of multiwalled carbon nanotubes meanwhile maintaining excellent rate capabilities (60-80% retention at 50 A g(-1)). For the first time, all-graphene-based films (AGFs) are fabricated via the intercalation of GNSs into graphene layers. The AGF exhibits a capacitance of 166.8 F g(-1) at 1 A g(-1) and rate capability (83.9% retention at 50 A g(-1)) better than those of pure reduced graphene oxide (RGO) films and carbon nanotubes/graphene hybrid films (CGFs). PMID- 26669428 TI - Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice. AB - Cocaine addiction is associated with devastating medical consequences, including cardiotoxicity and risk-conferring prolongation of the QT interval. Viral gene transfer of cocaine hydrolase engineered from butyrylcholinesterase offers therapeutic promise for treatment-seeking drug users. Although previous preclinical studies have demonstrated benefits of this strategy without signs of toxicity, the specific cardiac safety and efficacy of engineered butyrylcholinesterase viral delivery remains unknown. Here, telemetric recording of electrocardiograms from awake, unrestrained mice receiving a course of moderately large cocaine doses (30 mg/kg, twice daily for 3 weeks) revealed protection against a 2-fold prolongation of the QT interval conferred by pretreatment with cocaine hydrolase vector. By itself, this prophylactic treatment did not affect QT interval duration or cardiac structure, demonstrating that viral delivery of cocaine hydrolase has no intrinsic cardiac toxicity and, on the contrary, actively protects against cocaine-induced QT prolongation. PMID- 26669430 TI - Effects of supplementation with a calcium-rich marine-derived multi-mineral supplement and short-chain fructo-oligosaccharides on serum lipids in postmenopausal women. AB - Recent literature suggests that Ca supplements have adverse effects on cardiovascular health. The effects of a Ca-rich supplement administered alone or in combination with short-chain fructo-oligosaccharides (scFOS) on serum lipids in postmenopausal women were examined using secondary data from a 24-month double blind randomised controlled study. A total of 300 postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca (2.4 g Aquamin) (Ca), 800 mg of Ca with 3 g of scFOS (CaFOS) or control (maltodextrin) (MD). A full lipid profile, body composition, blood pressure and a range of cytokines were measured at baseline and after 24 months. Intention-to-treat ANCOVA assessed treatment effects between the groups. A significant time-by-treatment effect was observed for LDL and total cholesterol for the Ca and CaFOS groups, with both groups having lower LDL and total cholesterol concentrations compared with MD after 24 months. The control group had mean (5.2 mmol/l) total cholesterol concentrations above the normal range (<= 5 mmol/l) at 24 months, whereas values remained within the normal range in the treatment groups. There was no significant treatment effect on HDL-cholesterol, TAG, body composition, blood pressure or cytokine concentrations at 24 months, with the exception of IL-4, where there was a significant increase in the CaFOS group compared with the placebo. This study demonstrates a lipid-lowering effect of both the Ca-rich supplement alone and the supplement with scFOS. At the 4-year follow-up, there was no significant difference between the groups for reported diagnosed cardiovascular conditions. PMID- 26669432 TI - Pediatric Severe Sepsis/Septic Shock Associated with Healthcare-Associated Infections. PMID- 26669433 TI - Factors and outcomes associated with magnetic resonance cholangiopancreatography use before endoscopic retrograde cholangiopancreatography in patients at high risk for choledocholithiasis. PMID- 26669434 TI - Bayberry-like ZnO/MFI zeolite as high performance methanol-to-aromatics catalyst. AB - Unique bayberry-like MFI zeolites are synthesized through a quasi-solid-state crystallization approach. This hierarchical zeolite structure has a relatively thick shell, densely grown nanocrystals with an ordered packed channel, high mechanical stability, high surface area and a low Si/Al ratio. Its catalytic efficiency for methanol-to-aromatics is significantly higher than that of conventional MFI zeolites. PMID- 26669435 TI - Design, synthesis and optical properties of unsymmetrical subphthalocyanine trimer connected by phloroglucinol via axial positions. AB - An unsymmetrical subphthalocyanine trimer consisting of three different subphthalocyanine units was synthesized. Its optical and physical properties were investigated by UV/Vis, fluorescence spectrometry, cyclic voltammetry and computations. Energy transfer from the non-substituted subphthalocyanine unit to the perfluorinated subphthalocyanine unit via a trifluoroethoxy substituted unit is suggested. PMID- 26669436 TI - Orthotopic Liver Transplant for Budd-Chiari Syndrome: An Analysis of 14 Cases. AB - OBJECTIVES: Budd-Chiari syndrome is a low-prevalence, life-threatening disorder characterized by hepatic venous outflow obstruction at the hepatic venules, the large hepatic veins, the inferior vena cava, or the right atrium. Orthotopic liver transplant should be considered for patients with fulminant and chronic forms of the syndrome. MATERIALS AND METHODS: Fourteen patients received 15 orthotropic liver transplants at our center from September 2006 to March 2013. This study retrospectively reviewed the prospectively collected data from these 14 patients. RESULTS: The mean age of the patients was 33 years; only 1 patient was female. The severity of liver disease was Child-Pugh score A in 1 patient, B in 4 patients, and C in 9 patients. Mean calculated Model for End-Stage Liver Disease score was 18 (range, 6-30). The cause of Budd-Chiari syndrome was factor 5 Leiden mutation in 3 patients, polycythemia vera in 2 patients, factor 2 and 3 deficiency in 1 patient, fulminant essential thrombocytosis in 1 patient, and protein C deficiency in 2 patients. We performed 15 transplants in 14 patients. Five grafts were obtained from deceased donors, and 10 grafts were from living related donors. Mean graft-to-recipient weight ratio was 1,12 for patients receiving a living-donor liver transplant. Median follow-up was 29 months. Patient survival rates were 87%, 71%, and 71% at 1, 3, and 5 years. CONCLUSIONS: Liver transplant is an option for treating Budd-Chiari syndrome in cases of fulminant presentation and cirrhosis. Living-donor liver transplant is a viable choice in countries where procuring organ donations is still a problem. To manage the long-term medical therapy and follow-up for these patients, a careful evaluation is necessary to determine the cause of Budd-Chiari syndrome. Anticoagulant and antiaggregant therapy remains the mainstay of treatment for this syndrome. PMID- 26669437 TI - Effects of vibroacoustic stimulation in music therapy for palliative care patients: a feasibility study. AB - BACKGROUND: The present study aimed at examining whether methodological strategies from a previously implemented study design could be transferred to the evaluation of the psychological and physiological effects of a music therapy intervention working with vibroacoustic stimulation in palliative care. METHOD: Nine participants suffering from advanced cancer took part in single-sessions of music therapy, lasting for 30 min. The live music therapy intervention utilized singing chair sounds and vocal improvisation. Visual analogue scales (VAS) were used to assess self-ratings of pain, relaxation, and well-being before and after each session. During the intervention, we continuously recorded heart rate variability (HRV) as a measure of autonomic functioning. Data collection was complemented by a semi-structured interview to explore subjective experiences in more detail. Feasibility was defined as the ability to complete 80 % of the sessions in accordance with the study protocol. RESULTS: In 5 out of 9 sessions (55 %) it was possible to deliver the intervention and obtain all data as intended. VAS assessment was feasible, although graphical and statistical examination revealed only marginal mean changes between pre and post. HRV recordings were subject to artifacts. While HRV parameters differed between individuals, mean changes over time remained relatively constant. Interview data confirmed that the individual perception was very heterogeneous, ranging from "calming" to "overwhelming". CONCLUSION: The criterion of feasibility was not met in this study. Physiological data showed high attrition rates, most likely due to movement artifacts and reduced peripheral blood flow in some participants' extremities. Examination of individual-level trajectories revealed that vibroacoustic stimulation may have an impact on the autonomic response. However, the direction and mechanisms of effects needs to be further explored in future studies. TRIAL REGISTRATION: German Clinical Trials Register - DRKS00006137 (July 4(th), 2014). PMID- 26669438 TI - A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation. AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT. METHODS: We measured DNA methylation levels genome-wide at single-nucleotide resolution in peripheral blood of 85 HSCT donors, matched to recipients with various transplant outcomes, with Illumina Infinium HumanMethylation450 BeadChips. RESULTS: Using genome-wide DNA methylation profiling, we showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We discovered 31 DNA methylation marks in donors that associated with aGVHD severity status in recipients, and demonstrated strong predictive performance of these markers in internal cross-validation experiments (AUC = 0.98, 95% CI = 0.96 0.99). We replicated the top-ranked CpG classifier using an alternative, clinical DNA methylation assay (P = 0.039). In an independent cohort of 32 HSCT donors, we demonstrated the utility of the epigenetic classifier in the context of a T cell replete conditioning regimen (P = 0.050). CONCLUSIONS: Our findings suggest that epigenetic typing of HSCT donors in a clinical setting may be used in conjunction with HLA genotyping to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome. PMID- 26669439 TI - mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy. AB - Growth factors and nutrients enhance protein synthesis and suppress overall protein degradation by activating the protein kinase mammalian target of rapamycin (mTOR). Conversely, nutrient or serum deprivation inhibits mTOR and stimulates protein breakdown by inducing autophagy, which provides the starved cells with amino acids for protein synthesis and energy production. However, it is unclear whether proteolysis by the ubiquitin proteasome system (UPS), which catalyzes most protein degradation in mammalian cells, also increases when mTOR activity decreases. Here we show that inhibiting mTOR with rapamycin or Torin1 rapidly increases the degradation of long-lived cell proteins, but not short lived ones, by stimulating proteolysis by proteasomes, in addition to autophagy. This enhanced proteasomal degradation required protein ubiquitination, and within 30 min after mTOR inhibition, the cellular content of K48-linked ubiquitinated proteins increased without any change in proteasome content or activity. This rapid increase in UPS-mediated proteolysis continued for many hours and resulted primarily from inhibition of mTORC1 (not mTORC2), but did not require new protein synthesis or key mTOR targets: S6Ks, 4E-BPs, or Ulks. These findings do not support the recent report that mTORC1 inhibition reduces proteolysis by suppressing proteasome expression [Zhang Y, et al. (2014) Nature 513(7518):440 443]. Several growth-related proteins were identified that were ubiquitinated and degraded more rapidly after mTOR inhibition, including HMG-CoA synthase, whose enhanced degradation probably limits cholesterol biosynthesis upon insulin deficiency. Thus, mTOR inhibition coordinately activates the UPS and autophagy, which provide essential amino acids and, together with the enhanced ubiquitination of anabolic proteins, help slow growth. PMID- 26669440 TI - Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1. AB - MicroRNAs (miRNAs) play essential, conserved roles in diverse developmental processes through association with the miRNA-induced silencing complex (miRISC). Whereas fundamental insights into the mechanistic framework of miRNA biogenesis and target gene silencing have been established, posttranslational modifications that affect miRISC function are less well understood. Here we report that the conserved serine/threonine kinase, casein kinase II (CK2), promotes miRISC function in Caenorhabditis elegans. CK2 inactivation results in developmental defects that phenocopy loss of miRISC cofactors and enhances the loss of miRNA function in diverse cellular contexts. Whereas CK2 is dispensable for miRNA biogenesis and the stability of miRISC cofactors, it is required for efficient miRISC target mRNA binding and silencing. Importantly, we identify the conserved DEAD-box RNA helicase, CGH-1/DDX6, as a key CK2 substrate within miRISC and demonstrate phosphorylation of a conserved N-terminal serine is required for CGH 1 function in the miRNA pathway. PMID- 26669441 TI - The terminal phycobilisome emitter, LCM: A light-harvesting pigment with a phytochrome chromophore. AB - Photosynthesis relies on energy transfer from light-harvesting complexes to reaction centers. Phycobilisomes, the light-harvesting antennas in cyanobacteria and red algae, attach to the membrane via the multidomain core-membrane linker, L(CM). The chromophore domain of L(CM) forms a bottleneck for funneling the harvested energy either productively to reaction centers or, in case of light overload, to quenchers like orange carotenoid protein (OCP) that prevent photodamage. The crystal structure of the solubly modified chromophore domain from Nostoc sp. PCC7120 was resolved at 2.2 A. Although its protein fold is similar to the protein folds of phycobiliproteins, the phycocyanobilin (PCB) chromophore adopts ZZZssa geometry, which is unknown among phycobiliproteins but characteristic for sensory photoreceptors (phytochromes and cyanobacteriochromes). However, chromophore photoisomerization is inhibited in L(CM) by tight packing. The ZZZssa geometry of the chromophore and pi-pi stacking with a neighboring Trp account for the functionally relevant extreme spectral red shift of L(CM). Exciton coupling is excluded by the large distance between two PCBs in a homodimer and by preservation of the spectral features in monomers. The structure also indicates a distinct flexibility that could be involved in quenching. The conclusions from the crystal structure are supported by femtosecond transient absorption spectra in solution. PMID- 26669442 TI - Evolution of haploid selection in predominantly diploid organisms. AB - Diploid organisms manipulate the extent to which their haploid gametes experience selection. Animals typically produce sperm with a diploid complement of most proteins and RNA, limiting selection on the haploid genotype. Plants, however, exhibit extensive expression in pollen, with actively transcribed haploid genomes. Here we analyze models that track the evolution of genes that modify the strength of haploid selection to predict when evolution intensifies and when it dampens the "selective arena" within which male gametes compete for fertilization. Considering deleterious mutations, evolution leads diploid mothers to strengthen selection among haploid sperm/pollen, because this reduces the mutation load inherited by their diploid offspring. If, however, selection acts in opposite directions in haploids and diploids ("ploidally antagonistic selection"), mothers evolve to reduce haploid selection to avoid selectively amplifying alleles harmful to their offspring. Consequently, with maternal control, selection in the haploid phase either is maximized or reaches an intermediate state, depending on the deleterious mutation rate relative to the extent of ploidally antagonistic selection. By contrast, evolution generally leads diploid fathers to mask mutations in their gametes to the maximum extent possible, whenever masking (e.g., through transcript sharing) increases the average fitness of a father's gametes. We discuss the implications of this maternal-paternal conflict over the extent of haploid selection and describe empirical studies needed to refine our understanding of haploid selection among seemingly diploid organisms. PMID- 26669443 TI - Effects of DNA replication on mRNA noise. AB - There are several sources of fluctuations in gene expression. Here we study the effects of time-dependent DNA replication, itself a tightly controlled process, on noise in mRNA levels. Stochastic simulations of constitutive and regulated gene expression are used to analyze the time-averaged mean and variation in each case. The simulations demonstrate that to capture mRNA distributions correctly, chromosome replication must be realistically modeled. Slow relaxation of mRNA from the low copy number steady state before gene replication to the high steady state after replication is set by the transcript's half-life and contributes significantly to the shape of the mRNA distribution. Consequently both the intrinsic kinetics and the gene location play an important role in accounting for the mRNA average and variance. Exact analytic expressions for moments of the mRNA distributions that depend on the DNA copy number, gene location, cell doubling time, and the rates of transcription and degradation are derived for the case of constitutive expression and subsequently extended to provide approximate corrections for regulated expression and RNA polymerase variability. Comparisons of the simulated models and analytical expressions to experimentally measured mRNA distributions show that they better capture the physics of the system than previous theories. PMID- 26669444 TI - cAMP-induced phosphorylation of 26S proteasomes on Rpn6/PSMD11 enhances their activity and the degradation of misfolded proteins. AB - Although rates of protein degradation by the ubiquitin-proteasome pathway (UPS) are determined by their rates of ubiquitination, we show here that the proteasome's capacity to degrade ubiquitinated proteins is also tightly regulated. We studied the effects of cAMP-dependent protein kinase (PKA) on proteolysis by the UPS in several mammalian cell lines. Various agents that raise intracellular cAMP and activate PKA (activators of adenylate cyclase or inhibitors of phosphodiesterase 4) promoted degradation of short-lived (but not long-lived) cell proteins generally, model UPS substrates having different degrons, and aggregation-prone proteins associated with major neurodegenerative diseases, including mutant FUS (Fused in sarcoma), SOD1 (superoxide dismutase 1), TDP43 (TAR DNA-binding protein 43), and tau. 26S proteasomes purified from these treated cells or from control cells and treated with PKA degraded ubiquitinated proteins, small peptides, and ATP more rapidly than controls, but not when treated with protein phosphatase. Raising cAMP levels also increased amounts of doubly capped 26S proteasomes. Activated PKA phosphorylates the 19S subunit, Rpn6/PSMD11 (regulatory particle non-ATPase 6/proteasome subunit D11) at Ser14. Overexpression of a phosphomimetic Rpn6 mutant activated proteasomes similarly, whereas a nonphosphorylatable mutant decreased activity. Thus, proteasome function and protein degradation are regulated by cAMP through PKA and Rpn6, and activation of proteasomes by this mechanism may be useful in treating proteotoxic diseases. PMID- 26669445 TI - CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. AB - Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin alphaM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet-induced insulin resistance was significantly reduced in CD11b deficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity induced insulin resistance by limiting the proliferation and alternative activation of ATMs. PMID- 26669446 TI - "Stop eating lollies and do lots of sports": a prospective qualitative study of the development of children's awareness of dietary restraint and exercise to lose weight. AB - BACKGROUND: Beliefs surrounding the usefulness of dietary restriction and physical activity as means of body shape and size modification is already present in children as young as 5-years-old, and these beliefs may increase the risk of unhealthy weight control behaviours later in life. To date, however, little is known regarding the development of these beliefs in younger children. The aim of the present study was, therefore, to explore young (aged 3- to 5-years old) children's conceptualisations of dietary restriction and physical activity as means to change body size using a prospective approach. METHODS: A sample of 259 children (116 boys, 143 girls) participated in interviews at 3-, 4- and 5-years old. Participants were shown silhouette figures of a child of their gender and age. Their responses to questions regarding how the figure could return to a previous thinner shape were qualitatively coded using thematic analysis. RESULTS: Children's responses revealed that while, for a subsample, modifications of food, eating, and exercise patterns were the most salient ideas, a number of other mechanisms of body change were also suggested. Responses also evidenced adoption or awareness of stigmatising attitudes towards overweight individuals (over 15% by age 5). The proportion of children demonstrating an awareness of dietary restriction and physical exercise as methods for body size change increased significantly at each time point. While only 4.2% demonstrated dieting awareness at 3-years-old, this proportion had risen to almost 28% by 5-years-old (p < .001). Similarly, the proportion of children aware of exercise as a body change strategy rose from 2.3 to 16.3% (p < .001), with 22% of 5-year-olds mentioning general physical activity as a strategy. No gender differences were found. CONCLUSIONS: Awareness of dietary restriction and physical exercise as strategies for weight loss and body change emerges as young as 3-years-old, and significantly increases from 3- to 5-years-old. Interventions aiming to promote healthy means of weight control and obesity prevention should consider that certain attitudes may already be present in very young children. PMID- 26669447 TI - Production of Oxidation-Resistant Cu-Based Nanoparticles by Wire Explosion. AB - The low performance or high cost of commercially available conductive inks limits the advancement of printed electronics. This article studies the explosion of metal wires in aqueous solutions as a simple, low-cost, and environmentally friendly method to prepare metallic nanoparticles consisting of Cu and Cu alloys for use in affordable, highly conductive inks. Addition of 0.2 M ascorbic acid to an aqueous explosion medium prevented the formation of Cu2O shells around Cu nanoparticles, and allowed for the printing of conductive lines directly from these nanoparticles with no post-treatment. Cu alloy nanoparticles were generated from metal wires that were alloyed as purchased, or from two wires of different metals that were twisted together. Cu nanoparticles alloyed with 1% Sn, 5% Ag, 5% Ni and 30% Ni had electrical conductivities similar to Cu but unlike Cu, remained conductive after 24 hrs at 85 degrees C and 85% RH. PMID- 26669449 TI - PARP inhibitors in ovarian cancer. PMID- 26669448 TI - Nudix hydrolases degrade protein-conjugated ADP-ribose. AB - ADP-ribosylation refers to the transfer of the ADP-ribose group from NAD(+) to target proteins post-translationally, either attached singly as mono(ADP-ribose) (MAR) or in polymeric chains as poly(ADP-ribose) (PAR). Though ADP-ribosylation is therapeutically important, investigation of this protein modification has been limited by a lack of proteomic tools for site identification. Recent work has demonstrated the potential of a tag-based pipeline in which MAR/PAR is hydrolyzed down to phosphoribose, leaving a 212 Dalton tag at the modification site. While the pipeline has been proven effective by multiple groups, a barrier to application has become evident: the enzyme used to transform MAR/PAR into phosphoribose must be purified from the rattlesnake Crotalus adamanteus venom, which is contaminated with proteases detrimental for proteomic applications. Here, we outline the steps necessary to purify snake venom phosphodiesterase I (SVP) and describe two alternatives to SVP-the bacterial Nudix hydrolase EcRppH and human HsNudT16. Importantly, expression and purification schemes for these Nudix enzymes have already been proven, with high-quality yields easily attainable. We demonstrate their utility in identifying ADP-ribosylation sites on Poly(ADP-ribose) Polymerase 1 (PARP1) with mass spectrometry and discuss a structure-based rationale for this Nudix subclass in degrading protein-conjugated ADP-ribose, including both MAR and PAR. PMID- 26669450 TI - PARP inhibitors in ovarian cancer: Clinical evidence for informed treatment decisions. AB - Ovarian cancer is the fifth leading cause of female cancer deaths in the Western world. Significant progress has been made in the treatment of patients with ovarian cancer, however, the majority of patients experience disease recurrence and new therapies are being sought for such patients. Clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment has demonstrated promising activity in this disease. Here, we review the development of PARP inhibitors and their future role in the treatment of patients with ovarian cancer. Studies of olaparib, the first PARP inhibitor to be approved in Europe and the USA, in patients with recurrent ovarian cancer have demonstrated clinical efficacy with improvements in progression-free survival. In maintenance therapy of platinum-sensitive ovarian cancer there is supporting evidence of clinical benefit from exploratory endpoints that include time to first subsequent treatment and time to second subsequent treatment. Adverse events that should be monitored following treatment with PARP inhibitors include nausea, vomiting, fatigue and anaemia. Based on the evidence presented, patients who will receive the greatest benefit from PARP inhibition are those with platinum-sensitive relapsed ovarian cancer and a BRCA mutation. PMID- 26669451 TI - UK BRCA mutation testing in patients with ovarian cancer. AB - Despite the increasing clinical importance of germline BRCA mutation status in managing women with ovarian cancer, few patients are currently being tested. The traditional means of selecting patients for BRCA mutation testing using restrictive criteria will miss many women with a mutation. To expand access to testing and streamline the testing process, several centres in the UK have been developing new models for BRCA testing. Trials with these integrated models involving closer collaborations between genetics and oncology services are now under way. In addition to testing for BRCA mutations, there is also increasing interest in testing for other genes associated with a predisposition to ovarian cancer. Advances in next-generation sequencing technology have resulted in the development of comprehensive genetic testing panels for use in the research and diagnostic settings. Interest is also increasing in expanding testing for somatic mutations in ovarian cancer, particularly for genes such as BRCA1 and BRCA2, whereby mutations may allow more patients to benefit from targeted agents, including poly(ADP-ribose) polymerase inhibitors. In this review, the issues of who should be offered testing, how testing could be delivered, when testing should occur and the technology and costs associated with genetic testing are addressed. PMID- 26669453 TI - Consistency of T2WI-FS/ASL fusion images in delineating the volume of nasopharyngeal carcinoma. AB - Tumor extent assessment of nasopharyngeal carcinoma (NPC) is critical for delineating the radiotherapeutic target region. We aimed to investigate the use of the fusion images of fat suppressed T2WI (T2WI-FS) with arterial spin labeling (ASL) in measuring the volume of NPC. Two observers measured the volume of 21 untreated NPC using T2WI-FS, T2WI-FS/ASL (with PLD = 1.0, 1.5 and 2.0 s) fusion images and enhanced T1WI separately. Correlation and consistency were used to compare 1) measurements using T2WI-FS/ASL and T2WI-FS alone, taking enhanced T1WI images as a benchmark; 2) measurements between observers. Significant correlations existed between different series (r: 0.896~0.973). Measurements from the two observers using T2WI-FS/ASL had relatively higher intra-class correlation (ICC) (0.980~0.997) and lower within-subject coefficients of variation (wsCV) (14.76%~22.96%) when compared to using T2WI-FS alone (ICC: 0.978, 0.951, wsCV: 21.61%, 24.21%), while the T2WI-FS/ASL 1.0 s exhibited the best performance. Remarkably high ICC value (0.981~0.996) and relatively low wsCV (9.95%~17.91%) were obtained for the two observers using same series. Compared to those obtained using T2WI-FS alone, measurements made using T2WI-FS/ASL were more consistent with those made using enhanced T1WI. The T2WI-FS/ASL fusion images has the potential to be an alternative to enhanced T1WI, when contrast administration can not be performed. PMID- 26669452 TI - The development of PARP inhibitors in ovarian cancer: from bench to bedside. AB - The nuclear enzyme poly (ADP-ribose) polymerase (PARP) represents an important novel target in the treatment of ovarian cancer. This article charts over 50 years of research from the discovery of the first PARP enzyme in 1963, to the approval and licensing in 2015 of the first PARP inhibitor, olaparib (Lynparza), in the treatment of BRCA-mutated ovarian cancer. PMID- 26669456 TI - Transient IR Spectroscopic Observation of Singlet and Triplet States of 2 Nitrofluorene: Revisiting the Photophysics of Nitroaromatics. AB - The dynamics of 2-nitrofluorene (2-NF) in deuterated acetonitrile is studied using UV pump, IR probe femtosecond transient absorption spectroscopy. Upon excitation to the vibrationally excited S1 state, the excited-state population of 2-NF branches into two different relaxation pathways. One route leads to intersystem crossing (ISC) to the triplet manifold within a few hundred femtoseconds and the other to internal conversion (IC) to the ground state. The experiments indicate that after relaxation to the energetic minimum on S1, 2-NF undergoes internal conversion to the ground state in about 15 ps. IC within the triplet manifold is also observed as the initially populated triplet state relaxes to T1 in about 6 ps. Rotational anisotropy measurements corroborate the assignment of the transient IR frequencies and indicate a rotational diffusion time of 2-NF in the solvent of about 14 ps. The combined set of results provides a unified picture of the dynamics in photoexcited 2-NF. This to our knowledge is the first example using femtosecond vibrational spectroscopy for the study of the fundamental photoinduced processes in nitroaromatic compounds. PMID- 26669454 TI - Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. AB - Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of 'metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. PMID- 26669458 TI - [Anterograde dissection of the facial nerve during parotidectomy: identification of the main trunk of the facial nerve]. PMID- 26669459 TI - [Mucosal Melanoma of the Head and Neck]. AB - Primary mucosal malignant melanoma of the head and neck is a rare tumor entity with poor clinical outcome. Its growth pattern is characterized by an infiltrative and local destructive behavior. So far no risk factors could be identified. There are practically no early symptoms of the disease, as intermitting nose bleeding or nasal obstruction typically occur in advanced stage. The standard of care remains radical tumor resection with adjuvant radiation in cases of close margin resection. Other therapeutic options like the use of interferon, antibodies or conventional chemotherapeutics have not demonstrated significant clinical benefit so far. Current efforts to investigate the biological and genomic characteristics of these tumors have been constrained by its low incidence. In order to better characterize this rare tumor entity and to establish effective novel targeted therapies it will be necessary to establish an interdisciplinary and multicentric task force. PMID- 26669455 TI - Melatonin Has An Ergogenic Effect But Does Not Prevent Inflammation and Damage In Exhaustive Exercise. AB - It is well documented that exhaustive physical exercise leads to inflammation and skeletal muscle tissue damage. With this in mind, melatonin has been acutely administered before physical exercise; nevertheless, the use of melatonin as an ergogenic agent to prevent tissue inflammation and damage remains uncertain. We evaluated the effects of melatonin on swimming performance, muscle inflammation and damage and several physiological parameters after exhaustive exercise at anaerobic threshold intensity (iLAn) performed during light or dark circadian periods. The iLAn was individually determined and two days later, the animals performed an exhaustive exercise bout at iLAn 30 minutes after melatonin administration. The exercise promoted muscle inflammation and damage, mainly during the dark period, and the exogenous melatonin promoted a high ergogenic effect. The expressive ergogenic effect of melatonin leads to longer periods of muscle contraction, which superimposes a possible melatonin protective effect on the tissue damage and inflammation. PMID- 26669460 TI - [Diagnostic Accuracy of the LiSe-DaZ for Children with Specific Language Impairment]. AB - OBJECTIVE: Currently, only few tests for the development of speech and language exist for bi- or multilingual children in Germany. One of those, the LiSe-DaZ (Linguistic performance measurement - German as a second language), was examined in a prospective study regarding its practicability and the sensitivity to detect children with specific language impairment in a group of children aged 5 to 7 who suffered from a severe language impairment according to clinical tests. MATERIAL AND METHODS: 74 children (mean age: 60 months; 46% monolingual German-speaking; 54% bi- or multilingual) with severe specific language impairment were examined with the LiSe-DaZ in addition to the clinical established diagnostic during their in-patient stay in the hospital. RESULTS: The children, on average, showed in the receptive language abilities (LiSe-DaZ vs. TROG-D), the expressive vocabulary (LiSe-DaZ vs. AWST-R or WWT) and in the use of prepositions (LiSe-DaZ vs. Ravensburger Dysgrammatical clinical trial) significantly (p<0,0005) better results in the LiSe-DaZ. Thus, the majority of children were diagnosed as language impaired by clinically established tests whereas the LiSe-DaZ considered the children's language development to be normal. This difference was consistently more prominent for children with German as a second language. CONCLUSIONS: Compared with the clinically established tests, the informative value of the LiSe-DaZ turned out to be insufficient. The LiSe-DaZ does not detect children with the need of language therapy. Nevertheless, a norming of the established speech tests for bi- or multilingual children would be desirable to avoid unfounded judgements. PMID- 26669461 TI - [In Process Citation]. PMID- 26669462 TI - [Non-allergic Rhinitis: Epidemiology, Diagnostic and Therapy]. AB - Non-allergic rhinitis is a heterogenous group of medical diseases without an IgE mediated pathophysiology. In this review, typical subgroups are presented with data regarding their frequency, clinical symptoms and recommendations for an effective and efficient diagnostic and therapeutic approach are indicated. The most common subtype is the non-allergic rhinopathy, also known as idiopathic or vasomotoric rhinitis. Because medication induced rhinitis is still a frequent clinical problem, a step wise approach to wean the patient is presented. PMID- 26669464 TI - [In Process Citation]. PMID- 26669465 TI - To quit or not: Vulnerability of women to smoking tobacco. AB - Tobacco smoking is currently on the rise among women, and can pose a greater health risk. In order to understand the nature of the increase in smoking prevalence among women, we focused on the vulnerability of women to smoking behaviors--smoking cessation or tobacco addiction--and performed a systematic review of the socioeconomic and intrinsic factors as well as tobacco ingredients that affect women's susceptibility to smoking tobacco. We observed that nicotine and other tobacco components including cocoa-relatives, licorice products, and menthol aggravate tobacco addiction in women rather than in men. Various genetic and epigenetic alterations in dopamine pathway and the pharmaco-kinetics and dynamic factors of nicotine also showed potential evidences for high susceptibility to tobacco addiction in women. Therefore, we suggest systemic approaches to prevent tobacco smoking-related health risks, considering gene environment-gender interaction. PMID- 26669466 TI - Remodeling in Allergic Rhinitis. Adding New Data to an Old Debate. PMID- 26669467 TI - Dyspnea: Don't Just Look, Ask! PMID- 26669468 TI - Macrophage Dysfunction in Cystic Fibrosis: A Therapeutic Target to Enhance Self Immunity. PMID- 26669469 TI - Aerobic Glycolysis and the Warburg Effect. An Unexplored Realm in the Search for Fibrosis Therapies? PMID- 26669470 TI - Personalizing Therapy in Idiopathic Pulmonary Fibrosis: A Glimpse of the Future? PMID- 26669471 TI - Preinvasive Endobronchial Lesions: Lung Cancer Precursors and Risk Markers? PMID- 26669472 TI - Peering into a Rejecting Lung: Can Bronchoalveolar Lavage Exosomes Provide Novel Insights? PMID- 26669473 TI - To Trach, or Not to Trach: That Is the Question. PMID- 26669474 TI - Underestimation of Patient Breathlessness by Nurses and Physicians during a Spontaneous Breathing Trial. AB - RATIONALE: Breathlessness is a prevalent and distressing symptom in intensive care unit patients. There is little evidence of the ability of healthcare workers to assess the patient's experiences of breathing. Patient perception of breathing is essential in symptom management, and patient perception during a spontaneous breathing trial (SBT) might be related to extubation success. OBJECTIVES: To assess mechanically ventilated patients' experiences of breathlessness during SBT. METHODS: This was a prospective observational multicenter study of 100 mechanically ventilated patients. We assessed the agreement between nurses, physicians, and patients' 11-point Numerical Rating Scales scores of breathlessness, perception of feeling secure, and improvement of respiratory function at the end of an SBT (most performed with some level of support). We also determined the association between breathlessness and demographic factors or respiratory observations. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients (62%) reported moderate or severe breathlessness (Numerical Rating Scales >= 4). The median intensity of breathlessness reported by patients was five compared with two by nurses and physicians (P < 0.001). Patients felt less secure and reported less improvement of respiratory function compared with nurses' and physicians' ratings. About half of the nurses and physicians underestimated breathlessness (difference score, <=-2) compared with the patients' self-reports. Underestimation of breathlessness was not associated with professional competencies. There were no major differences in objective assessments of respiratory function in patients with moderate or severe breathlessness, and no apparent relationship between breathlessness during the SBT and extubation outcome. CONCLUSIONS: Patients reported higher breathlessness after SBT compared with nurses and physicians. Clinical trial registered with www.clinicaltrials.gov (NCT 01928277). PMID- 26669475 TI - A Compartmentalized Profibrotic Immune Response Characterizes Pericardial Tuberculosis, Irrespective of HIV-1 Infection. PMID- 26669476 TI - Recovery of Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction after Smoking Cessation. PMID- 26669478 TI - Restless Legs Syndrome. PMID- 26669477 TI - Whether to Breathe Fast or Not: What Is Wrong with Breathing Control in Patients with Mild Obstructive Pulmonary Disease? PMID- 26669479 TI - A potential role for the dermatologist in the physical transformation of transgender people: A survey of attitudes and practices within the transgender community. AB - BACKGROUND: There are an estimated 700,000 or more transgender people in the United States, however their dermatologic needs are not fully established in the medical literature. Unique needs relate to hormone therapy, prior surgeries, and other aspects of physical transitioning. OBJECTIVES: By examining attitudes and practices of transgender individuals, we aimed to identify areas for which dermatologists could contribute to their physical transformation. METHODS: This cross-sectional study used an anonymous online survey, distributed via lesbian, gay, bisexual, and transgender organizations; social media; and at targeted locations and events. RESULTS: A total of 327 people completed the survey (63% men, 29% women, 9% other). Most transgender women indicated that their face was most imperative to have changed, whereas men noted their chest, in turn influencing procedures. Of women's facial procedures, hair removal predominated, followed by surgery then injectables, mostly performed by plastic surgeons. Hormone-induced facial effects varied, usually taking over 2 years for maximal effect. When choosing procedures, money was the major barrier and good aesthetic outcome the primary concern. Participants did not think that facial procedures necessitate the currently accepted prerequisites for chest and genital surgery. LIMITATIONS: This study has limited size and convenience sampling. CONCLUSION: Dermatologists could contribute to the physical transformation of transgender patients through noninvasive procedures. PMID- 26669480 TI - A morphometric study to establish criteria for fetal and neonatal cerebellar hypoplasia: A special emphasis on trisomy 18. AB - Cerebellar hypoplasia (CH) is one of the congenital abnormalities of the central nervous system and is seen in several diseases and syndromes. This study was conducted in order to examine methods for evaluating CH in fetus and neonate because CH has been diagnosed without any morphometric criteria at autopsy. We sampled 140 autopsied cases including nineteen trisomy 18 (T18), four non-T18 with presumed CH, and 117 control cases without any brain malformation. Statistical significance was present in the cerebellar weight and weight ratio of cerebellum per total brain between T18 and the control. The exponential regression models (ERM) showed that cerebral weight, cerebellar weight, and weight ratio of cerebellum per total brain increased gradually relative to gestational age in both T18 and the control. However, cerebellar weight and weight ratio of cerebellum per total brain of T18 showed growth delay with clear distinction between the two groups. The non-T18 with presumed CH showed similar results. Body weight, total brain, and gestational age should be considered totally when evaluating fetal and neonatal cerebellar development. Furthermore, the ERM results may be useful to evaluate the cerebellar development of fetus and neonate at autopsy. PMID- 26669481 TI - [U(bipy)4 ]: A Mistaken Case of U0 ? AB - After more than 50 years, the synthesis and electronic structure of the first and only reported "U0 complex" [U(bipy)4 ] (1) has been reinvestigated. Additionally, its one-electron reduced product [Na(THF)6 ][U(bipy)4 ] (2) has been newly discovered. High resolution crystallographic analyses combined with magnetic and computational data show that 1 and its derivative 2 are best described as highly reduced species containing mid-to-high-valent uranium ligated by redox non innocent ligands. PMID- 26669482 TI - [Hypertension and vascular risk: editorial for "Control of the major cardiovascular risk factors for ischemic cardiopathy in secondary prevention in Aragon: COCINA study". Impact of diabetes mellitus and its metabolic control with regards to cardiovascular risk]. PMID- 26669483 TI - [Influence of functional state in mortality of the elderly with hypertension]. PMID- 26669484 TI - Is there non-pharmacological treatment of hypertension? What is changed on hypertension treatment since Alderman in The Lancet 1994? PMID- 26669485 TI - [Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain]. AB - INTRODUCTION AND OBJECTIVE: Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). PATIENTS AND METHODS: We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. RESULTS: We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (+/-11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. CONCLUSIONS: H LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. PMID- 26669486 TI - Postsynthetic Modification of DNA Phosphodiester Backbone for Photocaged DNAzyme. AB - Photocaged (photoactivatable) biomolecules are powerful tools for noninvasive control of biochemical activities by light irradiation. DNAzymes (deoxyribozymes) are single-stranded oligonucleotides with a broad range of enzymatic activities. In this work, to construct photocaged DNAzymes, we developed a facile and mild postsynthetic method to incorporate an interesting photolabile modification (thioether-enol phosphate, phenol substituted, TEEP-OH) into readily available phosphorothioate DNA. Upon light irradiation, TEEP-OH transformed into a native DNA phosphodiester, and accordingly the DNAzymes with RNA-cleaving activities were turned "on" from its inactive and caged form. Activation of the TEEP-OH caged DNAzyme by light was also successful inside live cells. PMID- 26669494 TI - Magnetically separable ternary g-C3N4/Fe3O4/BiOI nanocomposites: Novel visible light-driven photocatalysts based on graphitic carbon nitride. AB - The present work demonstrates preparation of magnetically separable ternary g C3N4/Fe3O4/BiOI nanocomposites as novel visible-light-driven photocatalysts. The resultant samples were characterized using XRD, EDX, SEM, TEM, UV-Vis DRS, FT-IR, PL, BET, and VSM techniques. The results revealed that weight percent of BiOI has considerable effect on photodegradation of rhodamine B under visible-light irradiation. Among the prepared samples, the g-C3N4/Fe3O4/BiOI (20%) nanocomposite has the best photocatalytic activity. The activity of this nanocomposite is about 10, 22, and 21-fold higher than that of the g-C3N4 sample in degradation of rhodamine B, methylene blue, and methyl orange under the visible-light irradiation. The excellent activity of the magnetic nanocomposite was attributed to more harvesting of the visible-light irradiation and efficiently separation of the electron-hole pairs. More importantly, the nanocomposite was magnetically separated after five successive cycles. PMID- 26669487 TI - A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes. AB - In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jkappa, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous inactivation of RBP-Jkappa and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors. PMID- 26669488 TI - Comparison of myxobacterial diversity and evaluation of isolation success in two niches: Kiritimati Island and German compost. AB - Myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. The diversity of myxobacteria present in two ecological habitats, namely sand from Kiritimati Island and German compost, was evaluated by both cultivation-based and cultivation-independent methods. Phylogenetic analyses of the strains in comparison with 16S rRNA gene sequences from cultured and uncultured material in GenBank revealed a great potential of undescribed myxobacteria in both sampling sites. Several OTUs (operational taxonomic units) represent unknown taxa and were detected by clone bank analyses, but not by cultivation. Clone bank analyses indicated that the myxobacterial community is predominantly indigenous. The 16S rDNA libraries from the two samples were generated from total community DNA with myxobacterial specific forward and universal reverse primer sets. The clones were partially sequenced. Cultivation was successful for exclusively bacteriolytic, but not for cellulolytic myxobacteria and revealed 42 strains from the genera Corallococcus, Myxococcus, and Polyangium. The genera of Myxococcaceae family were represented by both approaches. But, even in this well studied family, as well as in the suborders Sorangiineae and Nannocystineae, a considerable number of clones were assigned to, if any, uncultivated organisms. Our study shows an overrepresentation of the genera Myxococcus spp. and Corallococcus spp. with standard cultivation methods. However, high deficits are demonstrated in the cultivation success of the myxobacterial diversity detected by exclusively cultivation-independent approaches. Especially, clades which are exclusively represented by clones are of high interest with regard to the cultivation of new bioactive secondary metabolite producers. PMID- 26669495 TI - Enhanced catalytic activity of the surface modified TiO2-MWCNT nanocomposites under visible light. AB - Fusing multiwall carbon nanotubes (MWCNTs) with TiO2 at the nano-scale level promotes the separation of those electron-hole charges generated upon UV and daylight irradiation. In this study, we investigated facile sonochemical synthesis, combined with the calcination process for the preparations of TiO2 MWCNT composites with different mole ratios of titanium and carbon. In order to produce stable nano dispersions we exploited an innovative biotechnology-based approach for the covalent functionalizations of TiO2-MWCNTs with in-situ synthesized soluble phenoxazine dye molecules. The none and functionalized TiO2 MWCNTs composites were analyzed by a range of analytical techniques including XRD, Raman, XPS, SEM and UV-vis diffuse reflectance spectroscopy (DRS), and dynamic light scattering (DLS). The photocatalytic activity was evaluated toward the liquid-phase degradation of MB in aqueous solution under both UV and visible light irradiation. TiO2-MWCNTs with optimized mole ratio exhibit much higher photocatalytic activity and stability than bare TiO2. The as-prepared TiO2-MWCNTs photocatalyst possessed good adsorptivity of dyes, extended light absorption range and efficient charge separation properties simultaneously. The results indicated that the soluble phenoxazine dyes and amino-benzenesulfonic acid monomers were covalently grafted on to the surfaces of TiO2-MCNTs, which promoted good aquatic dispersibility and extended light absorption, resulting in increased photocatalytic efficiency. PMID- 26669496 TI - Line printing solution-processable small molecules with uniform surface profile via ink-jet printer. AB - Line printing offers a feasible approach to remove the pixel well structure which is widely used to confine the ink-jet printed solution. In the study, a uniform line is printed by an ink-jet printer. To achieve a uniform surface profile of the printed line, 10vol% low-volatile solvent DMA (3,4-Dimethylanisole) is mixed with high-volatile solvent Pxy (p-xylene) as the solvent. After a solution processable small molecule is dissolved, the surface tension of DMA solution becomes lower than that of Pxy solution, which creates an inward Marangoni flow during the solvent evaporation. The inward Marangoni flow balances out the outward capillary flow, thereby forming a flat film surface. The line width of the printed line depends on the contact angle of the solution on the hole injection layer. PMID- 26669497 TI - Bi-functional Mo-doped WO3 nanowire array electrochromism-plus electrochemical energy storage. AB - Metal-doping is considered to be an effective way for construction of advanced semiconducting metal oxides with tailored physicochemical properties. Herein, Mo doped WO3 nanowire arrays are rationally fabricated by a sulfate-assisted hydrothermal method. Compared to the pure WO3, the optimized Mo-doped WO3 nanowire arrays exhibit improved electrochromic properties with fast switching speed (3.2s and 2.6s for coloration and bleaching, respectively), significant optical modulation (56.7% at 750nm, 83.0% at 1600nm and 48.5% at 10MUm), high coloration efficiency (123.5cm(2)C(-1)) and excellent cycling stability. In addition, as a proof of concept, the Mo-doped WO3 nanowire arrays are demonstrated with electrochemical energy storage monitored by the electrochromism. This electrode design protocol can provide an alternative way for developing high-performance active materials for bi-functional electrochromic batteries. PMID- 26669499 TI - Visible-Light-Induced Hydrodifluoromethylation of Alkenes with a Bromodifluoromethylphosphonium Bromide. AB - Bromodifluoromethylphosphonium bromide was solely used as the precursor of difluorocarbene. Herein, an unprecedented visible-light-induced hydrodifluoromethylation of alkenes with bromodifluoromethylphosphonium bromide using H2O and THF as hydrogen sources for the synthesis of difluoromethylated alkanes is described. This difluoromethylation is characterized by mild reaction conditions, ready availability of reagents, and excellent functional-group tolerance. PMID- 26669498 TI - [Effect of cognitive stimulation in elderly community]. AB - OBJECTIVE: To demonstrate that the implementation of the Cognitive Stimulation (CS) program 'Making a Difference' (MD) improves cognition and depressive symptoms in retired community elders. METHOD: This was a multicenter quasi experimental study of 45 community dwelling elders (38 women and 7 men), with a mean age of 75.29, from 3 day-care centers in rural, semi-rural and urban environments in the central region of Portugal. Participants attended 14 sessions twice a week over seven weeks. The Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale (GDS-15) were administered at the following three time points: baseline, post-test, and follow-up. RESULTS: From baseline to post-test, there is a statistically significant difference in depressive symptoms (F=7.494; P=.010) explaining 21% of the variance (partial eta squared [etap(2)]=.21), power=.75, but there is no statistically significant difference in cognition. From post-test to follow-up, there is no difference in both cognition and depression outcomes. CONCLUSIONS: Our results showed improvement in elders' depressive symptoms after a seven weeks intervention program but it did not have a protective effect after the three months follow-up. No evidence was found for its efficacy in improving cognition. Cognitive stimulation may be a useful in preventing elder's depressive symptoms when included in their health promotion care plan. PMID- 26669500 TI - Successful therapy of cyclosporin A in pityriasis lichenoides et varioliformis acuta preceded by hand, foot and mouth disease. AB - To our knowledge, there are no previously published cases of enteroviral infection complicated by pityriasis lichenoides et varioliformis acuta (PLEVA). A 30-year-old woman is reported with a severe form of PLEVA, preceded by hand, foot and mouth disease. Immunosuppressive treatment with cyclosporin A resulted in rapid clinical improvement. PMID- 26669501 TI - Simulated Wear of Self-Adhesive Resin Cements. AB - One of the primary areas of concern with luting agents is marginal gap erosion and attrition. The purpose of this laboratory study was to evaluate bulk and marginal slit (gap) generalized wear of self-adhesive resin cements. Three self adhesive resin cements were used in this study: G-CEM LinkAce (LA), Maxcem Elite (ME), and RelyX Unicem2 Automix (RU). A custom stainless-steel fixture with a cavity 4.5 mm in diameter and 4 mm deep was used for simulated generalized (bulk) wear. For simulated marginal gap wear, a two-piece stainless-steel custom fixture was designed with a slit (gap) 300 MUm wide and 3 mm in length. For both wear models, 20 specimens each for each of the three adhesive cements were made for both light-cure and chemical-cure techniques. The cured cements were polished with a series of carbide papers to a 4000-grit surface and subjected to 100,000 cycles using the slit (gap) wear model and 400,000 cycles for generalized (bulk) wear in a Leinfelder-Suzuki (Alabama machine) wear simulator (maximum load of 78.5 N). Flat-ended stainless-steel antagonists were used in a water slurry of poly(methylmethacrylate) beads for simulation of generalized contact-free area wear with both wear models. Before and after the wear challenges, the specimens were profiled with a Proscan 2100 noncontact profilometer, and wear (volume loss [VL] and mean facet depth [FD]) was determined using AnSur 3D software. Two-way analysis of variance (ANOVA) and Tukey post hoc tests were used for data analysis for the two wear models. Scanning electron microscopy (SEM) was used to examine polished surfaces of the resin cements and the worn surfaces after the wear challenges. The two-way ANOVA of VL using the generalized (bulk) wear model showed a significant effect among the three resin cement materials for the factor of resin cement (p<0.001) and the interaction of the cement and cure method (p<0.001), but not for the cure method (p=0.465). The two-way ANOVA for FD also found a significant difference for the factor of resin cement (p<0.001) and the interaction of the resin cement and cure method (p<0.001), but not for the cure method (p=0.277). The simulated generalized (bulk) wear for the light-cure groups was as follows: VL (mm(3)): RU 0.631 (0.094), LA 0.692 (0.112), and ME 1.046 (0.141) and FD (MUm): RU 43.6 (6.5), LA 47.0 (7.7), and ME 72.5 (9.9). The simulated generalized (bulk) wear for the chemical-cure groups was as follows: VL (mm(3)): LA 0.741 (0.105), RU 1.231 (0.234), and ME 1.305 (0.143) and FD (MUm): LA 50.7 (7.2), RU 84.5 (16.1), and ME 91.7 (10.2). Simulated wear using the slit (gap) model for the light-cure groups was as follows: VL (mm(3)): RU 0.030 (0.006), LA 0.031 (0.006), and ME 0.041 (0.009) and FD (MUm): RU 49.6 (5.7), LA 57.2 (8.4), and ME 70.9 (10.7). The wear values for the chemical-cure slit (gap) groups were as follows: VL (mm(3)): LA 0.031 (0.004), ME 0.038 (0.007), and RU 0.045 (0.009) and FD (MUm): LA 53.9 (6.7), ME 63.5 (9.1), and RU 74.2 (12.9). Pearson correlation tests revealed a strong relationship between the two wear models for the light-cure groups and a good relationship for the chemical-cure groups. The observations using SEM showed differences in filler particle shape and size among the cements and the resultant effect of the wear challenges. The worn surfaces of each cement were essentially the same for both light-cure and chemical-cure methods. The bulk wear model and new slit (gap) model for evaluation of simulated generalized wear of luting agents demonstrated significant differences (p<0.05) in relative wear among three self-adhesive resin cements and between visible light- and chemical-cure techniques. PMID- 26669502 TI - Effect of Cigarette Smoke on Resin Composite Bond Strength to Enamel and Dentin Using Different Adhesive Systems. AB - OBJECTIVE: To evaluate the microshear bond strength of composite resin restorations in dental blocks with or without exposure to cigarette smoke. METHOD: Eighty bovine dental blocks were divided into eight groups (n=10) according to the type of adhesive (Scotchbond Multi-Purpose, 3M ESPE, St Paul, MN, USA [SBMP]; Single Bond 2, 3M ESPE [SB]; Clearfil SE Bond, Kuraray Medical Inc, Okayama, Japan [CSEB]; Single Bond Universal, 3M ESPE [SBU]) and exposure to smoke (no exposure; exposure for five days/20 cigarettes per day). The adhesive systems were applied to the tooth structure, and the blocks received a composite restoration made using a matrix of perforated pasta. Data were statistically analyzed using analysis of variance and Tukey test (alpha<0.05). RESULTS: For enamel, there was no difference between the presence or absence of cigarette smoke (p=0.1397); however, there were differences among the adhesive systems (p<0.001). CSEB showed higher values and did not differ from SBU, but both were statistically different from SB. The SBMP showed intermediate values, while SB demonstrated lower values. For dentin, specimens subjected to cigarette smoke presented bond strength values that were lower when compared with those not exposed to smoke (p<0.001). For the groups without exposure to cigarette smoke, CSEB showed higher values, differing from SBMP. SB and SBU showed intermediary values. For the groups with exposure to cigarette smoke, SBU showed values that were higher and statistically different from SB and CSEB, which presented lower values of bond strength. SBMP demonstrated an intermediate value of bond strength. CONCLUSION: The exposure of dentin to cigarette smoke influenced the bonding strength of adhesives, but no differences were noted in enamel. PMID- 26669503 TI - Bleaching Effects on Color, Chemical, and Mechanical Properties of White Spot Lesions. AB - OBJECTIVE: The purpose of the study was to evaluate the effect of bleaching on teeth with white spot lesions. METHODS AND MATERIALS: Carious lesions with standardized whiteness were produced on the buccal and lingual surfaces of human premolars by pH cycling. Specimens were subjected to four experimental conditions (n=20/group) as follows: group 1, control; group 2, caries formation followed by remineralization using fluoride-containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP; Tooth Mousse Plus, GC, Tokyo, Japan); group 3, caries formation followed by bleaching using 10% carbamide peroxide; and group 4, caries formation followed by both bleaching and remineralization. The CIE L(*)a(*)b(*) color values were measured with a spectroradiometer, the mineral content was measured with electron probe microanalysis (EPMA) on the cross-sectional surface of each specimen, and the Knoop hardness test was carried out along the EPMA scan line. Two-way analysis of variance was performed with Tukey post hoc comparison. RESULTS: The change in the CIE color values was not significantly different between the caries-formed (DeltaE(*)=7.03) and the bleached enamel (DeltaE(*)=7.60). Bleaching of the carious enamel extended the whiteness (DeltaE(*)=3.38) without additional mineral loss (p<0.05). The remineralization treatment significantly increased the calcium (Ca), phosphate (P), and fluoride content of the subsurface lesion area (p<0.05). The cross-sectional microhardness values correlated well with the Ca and P content (R>0.80). CONCLUSIONS: Bleaching reduced the color disparities between sound and carious enamel without deteriorating the chemical and mechanical properties. The application of CPP-ACP paste enhanced mineral deposition in the subsurface lesion area of carious enamel. PMID- 26669504 TI - Two-year Randomized Clinical Trial of Self-etching Adhesives and Selective Enamel Etching. AB - OBJECTIVE: The aim of this randomized, controlled prospective clinical trial was to evaluate the clinical effectiveness of restoring noncarious cervical lesions with two self-etching adhesive systems applied with or without selective enamel etching. METHODS: A one-step self-etching adhesive (Xeno V(+)) and a two-step self-etching system (Clearfil SE Bond) were used. The effectiveness of phosphoric acid selective etching of enamel margins was also evaluated. Fifty-six cavities were restored with each adhesive system and divided into two subgroups (n=28; etch and non-etch). All 112 cavities were restored with the nanohybrid composite Esthet.X HD. The clinical effectiveness of restorations was recorded in terms of retention, marginal integrity, marginal staining, caries recurrence, and postoperative sensitivity after 3, 6, 12, 18, and 24 months (modified United States Public Health Service). RESULTS: The Friedman test detected significant differences only after 18 months for marginal staining in the groups Clearfil SE non-etch (p=0.009) and Xeno V(+) etch (p=0.004). One restoration was lost during the trial (Xeno V(+) etch; p>0.05). CONCLUSIONS: Although an increase in marginal staining was recorded for groups Clearfil SE non-etch and Xeno V(+) etch, the clinical effectiveness of restorations was considered acceptable for the single step and two-step self-etching systems with or without selective enamel etching in this 24-month clinical trial. PMID- 26669505 TI - How does 3D endovaginal ultrasound compare to magnetic resonance imaging in the evaluation of levator ani anatomy? AB - INTRODUCTION AND HYPOTHESIS: To compare magnetic resonance imaging (MRI) to 3D endovaginal ultrasound (EVUS) in the evaluation of major levator ani defects in women with pelvic floor disorders. METHODS: A total of 21 subjects with pelvic floor with complaints of pelvic floor disorders were included in this study. EVUS imaging of the levator ani muscle (LAM) was performed in all subjects, and the LA muscle groups of interest evaluated were the puboanalis (PA), puborectalis (PR), and pubovisceralis (PV) muscles. The right and left subdivisions were evaluated separately, and classified as (i) normal, normal with only minor irregularities, grossly abnormal, or absent, or (ii) by the levator ani deficiency (LAD) score and classified by no defect (complete attachment of muscle to the pubic bone), <50% detachment or loss, >50% detachment or loss, and completely detached or complete muscle loss. Paired data were analyzed with McNemar's test or Bowker's test of symmetry. RESULTS: When unilateral LAM subdivisions were classified as "normal," "normal with minor irregularity," "grossly abnormal," and "absent," there were no significant differences between MRI and EVUS by categorization of LAM defects. Comparing "normal" versus "abnormal," there was no difference between imaging modalities. When compared by LAD score evaluation, there were no differences in the categorization of unilateral defects between MRI and EVUS. CONCLUSIONS: Endovaginal 3D US is comparable to MRI in its ability to identify both normal and abnormal LAM anatomy. Neurourol. Urodynam. 36:409-413, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26669506 TI - Farnesol increases the susceptibility of Burkholderia pseudomallei biofilm to antimicrobials used to treat melioidosis. AB - AIMS: The aim of this study was to analyse the in vitro activity of farnesol alone and combined with the antibacterial drugs amoxicillin, doxycycline, ceftazidime and sulfamethoxazole-trimethoprim against Burkholderia pseudomallei biofilms. METHODS AND RESULTS: Susceptibility was assessed by the broth microdilution test and cell viability was read with the oxidation-reduction indicator dye resazurin. The biofilms were evaluated through three microscopic techniques (optical, confocal and electronic microscopy). The minimum biofilm erradication concentration (MBEC) for farnesol was 75-2400 mmol l(-1). In addition, farnesol significantly reduced the MBEC values for ceftazidime, amoxicillin, doxycycline and sulfamethoxazole-trimethoprim by 256, 16, 4 and 4 times respectively (P < 0.05). Optical, confocal and electronic microscopic analyses of farnesol-treated B. pseudomallei biofilms demonstrated that this compound damages biofilm matrix, probably facilitating antimicrobial penetration in the biofilm structure. CONCLUSIONS: This study demonstrated the effectiveness of farnesol against B. pseudomallei biofilms and its potentiating effect on the activity of antibacterial drugs, in particular ceftazidime, amoxicillin, doxycycline and sulfamethoxazole-trimethoprim. SIGNIFICANCE AND IMPACT OF THE STUDY: The intrinsic antimicrobial resistance of B. pseudomallei is a serious challenge for the treatment of melioidosis. Thus, this paper reports the inhibitory potential of farnesol against B. pseudomallei biofilms, as well as highlights the favourable pharmacological interaction of farnesol with antibiotics tested, not only on cell viability, but also in the structural morphology of biofilms. PMID- 26669507 TI - Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering. AB - Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol(r) ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017. PMID- 26669508 TI - Structural Diversity and Properties of M(II) Coordination Compounds Constructed by 3-Hydrazino-4-amino-1,2,4-triazole Dihydrochloride as Starting Material. AB - Twelve metal coordination compounds with two triazole derivatives, namely, {[Mn(HATr)2](ClO4)2}n (1), [Mn(HATr)3]Cl(ClO4) (2), [Co3(ATr)6(H2O)6](ClO4)6.4.5H2O (3), [Co(HATr)3]Cl(ClO4) (4), [Co2Cl2(HATr)2(H2O)2(CH3OH)2]Cl2.2H2O (5), [Ni3(ATr)6(H2O)6](ClO4)6.4.5H2O (6), [Ni(HATr)3]Cl(ClO4) (7), [Ni2Cl2(HATr)2(H2O)4](ClO4)2.4H2O (8), [Ni2(HATr)2(H2O)6](ClO4)4.2H2O (9), {[Zn(HATr)2](ClO4)2}n (10), [Zn(HATr)3]Cl(ClO4) (11), and {[Cd4(HATr)8](CdCl4)Cl2(ClO4)4}n (12), when HATr = 3-hydrazino-4-amino-1,2,4-triazole and ATr = 4-amino-1,2,4-triazole, were prepared under diverse conditions and structurally characterized. Compounds 1, 10 and 12 exhibit one-dimensional zigzag chain structures; 2, 4, 7, and 11 possess mononuclear structures; 3 and 6 display trinuclear structures, while 5, 8, and 9 feature binuclear structures. Hydrogen bonds link these compounds into three dimensional structures. The thermal stability and energetic properties also were determined. PMID- 26669509 TI - Parallel Spectral Acquisition with an Ion Cyclotron Resonance Cell Array. AB - Mass measurement accuracy is a critical analytical figure-of-merit in most areas of mass spectrometry application. However, the time required for acquisition of high-resolution, high mass accuracy data limits many applications and is an aspect under continual pressure for development. Current efforts target implementation of higher electrostatic and magnetic fields because ion oscillatory frequencies increase linearly with field strength. As such, the time required for spectral acquisition of a given resolving power and mass accuracy decreases linearly with increasing fields. Mass spectrometer developments to include multiple high-resolution detectors that can be operated in parallel could further decrease the acquisition time by a factor of n, the number of detectors. Efforts described here resulted in development of an instrument with a set of Fourier transform ion cyclotron resonance (ICR) cells as detectors that constitute the first MS array capable of parallel high-resolution spectral acquisition. ICR cell array systems consisting of three or five cells were constructed with printed circuit boards and installed within a single superconducting magnet and vacuum system. Independent ion populations were injected and trapped within each cell in the array. Upon filling the array, all ions in all cells were simultaneously excited and ICR signals from each cell were independently amplified and recorded in parallel. Presented here are the initial results of successful parallel spectral acquisition, parallel mass spectrometry (MS) and MS/MS measurements, and parallel high-resolution acquisition with the MS array system. PMID- 26669511 TI - Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells. AB - The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3 BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT 20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer. PMID- 26669510 TI - Heart rate variability during daytime naps in healthy adults: Autonomic profile and short-term reliability. AB - In healthy individuals, a reduction in cardiovascular output and a shift to parasympathetic/vagal dominant activity is observed across nocturnal sleep. This cardiac autonomic profile, often measured by heart rate variability (HRV), has been associated with significant benefits for the cardiovascular system. However, little is known about the autonomic profile during daytime sleep. Here, we investigated the autonomic profile and short-term reliability of HRV during daytime naps in 66 healthy young adults. Participants took an 80-120 min polysomnographically recorded nap at 1:30 pm. Beat-by-beat RR interval values (RR), high (HF) and low frequency (LF) power, total power (TP), HF normalized units (HF(nu)), and the LF/HF ratio were obtained for 5 min during presleep wakefulness and during nap sleep stages (N2, N3, REM). A subsample of 37 participants took two additional naps with 2 weeks between recordings. We observed lengthening of the RR, higher HF and HF(nu), and lower LF/HF during NREM, compared with REM and wake, and a marked reduction of LF and TP during N3. Intraclass correlation coefficients highlighted a short-term stability of RR and HF ranging across sleep stages between 0.52-0.76 and 0.52-0.80, respectively. Our results suggest that daytime napping in healthy young adults is associated with dynamic changes in the autonomic profile, similar to those seen during nocturnal sleep. Moreover, a reliable intraindividual measure of autonomic cardiac activity can be obtained by just a single daytime nap depending on specific parameters and recording purposes. Nap methodology may be a new and promising tool to explore sleep-dependent, autonomic fluctuations in healthy and at-risk populations. PMID- 26669512 TI - HPV testing for primary cervical screening: Laboratory issues and evolving requirements for robust quality assurance. AB - This review aims to highlight the importance of Quality Assurance for Laboratories performing HPV test for Cervical Cancer Screening. An HPV test, to be used as primary screening test, must be validated according to international criteria, based on comparison of its clinical accuracy to HC2 or GP5+/6+ PCR-EIA tests. The number of validated platforms is increasing and appropriate Quality Assurance Programs (QAPs) which can interrogate longitudinal robustness and quality are paramount. This document describes the following topics: (1) the characteristics of an HPV laboratory and the personnel training needs, to ensure an elevated quality of the entire process and the optimal use of the resources; (2) the Quality Assurance, as both internal (IQA) and external quality assessment (EQA) systems, to be implemented and performed, and the description of the existing EQAs, including limitations; (3) general considerations for an optimal EQA program for hrHPV primary screening Due to the importance of Quality Assurance for this field, international efforts are necessary to improve QA International Collaboration. PMID- 26669513 TI - Investigation on the interaction of letrozole with herring sperm DNA through spectroscopic and modeling methods. AB - The interaction of letrozole, an efficient and safe aromatase inhibitor, with herring sperm DNA (hsDNA) was investigated in vitro through spectroscopy analysis and molecular modeling to elucidate the binding mechanism of anticancer drugs and DNA. The binding constant and the number of binding sites were 2.13 * 10(4) M( 1) and 1.09, respectively, at 298 K. Thermodynamic parameters (DeltaG, DeltaH and DeltaS) exhibited negative values, which indicated that binding was spontaneous and Van der Waals forces and hydrogen bond were the main interaction forces. Fourier transform infrared spectroscopy and other spectroscopy analysis methods illustrated that letrozole could intercalate into the phosphate backbone of hsDNA and interact with the nitrogenous bases. Consistent with the experimental findings, molecular modeling results demonstrated that the interaction was dominated by intercalation and hydrogen bonding. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669514 TI - Metabolic Fate of Hallucinogenic NBOMes. AB - 2,5-Dimethoxy-N-benzylphenethylamines (NBOMes) are very potent 5-HT2AR agonists. Illicit use of these psychedelic compounds has emerged in recent years, and several fatalities have been linked to their recreational use. In its [(11)C] labeled form, one NBOMe (25B-NBOMe) was recently developed as a PET-ligand for clinical investigations of 5HT2AR ([(11)C]Cimbi-36). Herein, we have identified the phase I and phase II metabolites of 25B-NBOMe in pigs as well as in humans. We find that the primary route of metabolism is 5'-demethylation, followed by conjugation to glucuronic acid. Carbon-11 labeling of 25B-NBOMe in three different positions followed by in vivo evaluation in pigs and humans corroborated these findings. PMID- 26669515 TI - The Arabidopsis thaliana CLAVATA3/EMBRYO-SURROUNDING REGION 26 (CLE26) peptide is able to alter root architecture of Solanum lycopersicum and Brassica napus. AB - Optimal development of root architecture is vital to the structure and nutrient absorption capabilities of any plant. We recently demonstrated that AtCLE26 regulates A. thaliana root architecture development, possibly by altering auxin distribution to the root apical meristem via inhibition of protophloem development. In addition, we showed that AtCLE26 application is able to induce a root architectural change in the monocots Brachypodium distachyon and Triticum aestivum. Here, we showed that application of the synthetic AtCLE26 peptide similarly affects other important agricultural species, such as Brassica napus and Solanum lycopersicum. PMID- 26669516 TI - An Automated Miniaturized Method to Perform and Analyze Antimicrobial Drug Synergy Assays. AB - In the light of emerging antibiotic resistance mechanisms found in bacteria throughout the world, discovery of drugs that potentiate the effect of currently available antibiotics remains an important aspect of pharmaceutical research in the 21st century. Well-established clinical tests exist to determine synergy in vitro, but these are only optimal for low-throughput experimentation while leaving analysis of results and interpretation of high-throughput microscale assays poorly standardized. Here, we describe a miniaturized broth microdilution checkerboard assay and data analysis method in 384-well plate format that conforms to the Clinical Laboratory and Standards Institute (CLSI) methods. This method has been automated and developed to rapidly determine the synergism of current antibiotics with various beta-lactamase inhibitors emerging from our antimicrobial research efforts. This technique increases test throughput and integrity of results, and saves test compound and labor. We facilitated the interpretation of results with an automated analysis tool allowing us to rapidly qualify inter- and intraplate robustness, determine efficacy of multiple antibiotics at the same time, and standardize the results of synergy interpretation. This procedure should enhance high-throughput antimicrobial drug discovery and supersedes former techniques. PMID- 26669517 TI - Controlling Material Reactivity Using Architecture. AB - 3D-printing methods are used to generate reactive material architectures. Several geometric parameters are observed to influence the resultant flame propagation velocity, indicating that the architecture can be utilized to control reactivity. Two different architectures, channels and hurdles, are generated, and thin films of thermite are deposited onto the surface. The architecture offers an additional route to control, at will, the energy release rate in reactive composite materials. PMID- 26669518 TI - Old tools revisited give hope - new treatment option for families with a history of severe FNAIT complications. PMID- 26669520 TI - Taming of 3,4-Di(nitramino)furazan. AB - Highly energetic 3,4-di(nitramino)furazan (1, DNAF) was synthesized and confirmed structurally by using single-crystal X-ray diffraction. Its highly sensitive nature can be attributed to the shortage of hydrogen-bonding interactions and an interactive nitro chain in the crystal structure. In order to stabilize this structure, a series of corresponding nitrogen-rich salts (3-10) has been prepared and fully characterized. Among these energetic materials, dihydrazinium 3,4 dinitraminofurazanate (5) exhibits a very promising detonation performance (nuD = 9849 m s(-1); P = 40.9 GPa) and is one of the most powerful explosives to date. To ensure the practical applications of 5, rather than preparing the salts of 1 through acid-base reactions, an alternative route through the nitration of N ethoxycarbonyl-protected 3,4-diaminofurazan and aqueous alkaline workup was developed. PMID- 26669521 TI - Integrity without extinction: paths forward for gambling research. PMID- 26669522 TI - Gambling with interests. PMID- 26669523 TI - Fine-tuning Livingstone and Adams' ethical principles for integrity in gambling research. PMID- 26669519 TI - An elevated amniotic fluid prostaglandin F2alpha concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes. AB - OBJECTIVE: To determine whether an elevated amniotic fluid concentration of prostaglandin F2alpha (PGF2alpha) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. MATERIALS AND METHODS: The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2alpha was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2alpha concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (>=170 pg/mL). RESULTS: (1) The prevalence of an elevated amniotic fluid PGF2alpha concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2alpha concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2alpha (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2alpha concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. CONCLUSION: The concentration of PGF2alpha was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis. PMID- 26669524 TI - The other side of the firewall. PMID- 26669525 TI - Response to commentaries-clear principles for gambling research. PMID- 26669526 TI - Commentary on Savell et al. (2016): Alcohol producers as problem inducers. PMID- 26669527 TI - Commentary on Mounteney et al. (2016): What drug monitoring systems need in 2015. PMID- 26669528 TI - Commentary on Cousins et al. (2016): Accumulating evidence on risk of mortality on and off opioid substitution treatment. PMID- 26669529 TI - Commentary on Salom et al. (2016): Early onset substance use-a key target for prevention and early intervention. PMID- 26669530 TI - Working towards an international consensus on criteria for assessing internet gaming disorder: a critical commentary on Petry et al. (2014). PMID- 26669531 TI - Griffiths et al.'s comments on the international consensus statement of internet gaming disorder: furthering consensus or hindering progress? PMID- 26669534 TI - A Rational Design, Synthesis, Biological Evaluation and Structure--Activity Relationship Study of Novel Inhibitors against Cyanobacterial Fructose-1,6 bisphosphate Aldolase. AB - In the present study, a series of novel maleimide derivatives were rationally designed and optimized, and their inhibitory activities against cyanobacteria class-II fructose-1,6-bisphosphate aldolase (Cy-FBA-II) and Synechocystis sp. PCC 6803 were further evaluated. The experimental results showed that the introduction of a bigger group (Br, Cl, CH3, or C6H3-o-F) on the pyrrole-2',5' dione ring resulted in a decrease in the Cy-FBA-II inhibitory activity of the hit compounds. Generally, most of the hit compounds with high Cy-FBA-II inhibitory activities could also exhibit high in vivo activities against Synechocystis sp. PCC 6803. Especially, compound 10 not only shows a high Cy-FBA-II activity (IC50 = 1.7 MUM) but also has the highest in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.6 ppm). Thus, compound 10 was selected as a representative molecule, and its probable interactions with the surrounding important residues in the active site of Cy-FBA-II were elucidated by the joint use of molecular docking, molecular dynamics simulations, ONIOM calculations, and enzymatic assays to provide new insight into the binding mode of the inhibitors and Cy-FBA-II. The positive results indicate that the design strategy used in the present study is very likely to be a promising way to find novel lead compounds with high inhibitory activities against Cy-FBA-II in the future. The enzymatic and algal inhibition assays suggest that Cy-FBA-II is very likely to be a promising target for the design, synthesis, and development of novel specific algicides to solve cyanobacterial harmful algal blooms. PMID- 26669535 TI - Development of genome-wide microsatellite resources in a commercially important mussel species (Mytilus chilensis). PMID- 26669536 TI - Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response. AB - According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 * 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity. PMID- 26669538 TI - SOCIAL ENGAGEMENT AND USE OF HYPERTENSIVE MEDICATION AMONG ADULTS IN CHINA. AB - This study's objectives were, first, to examine the association between social engagement and the odds of taking hypertensive medications and treatment among adults in China; and second, to explore the lifestyle and psychological mechanisms underlying this association. Data were from the WHO Study on Global AGEing and Adult Health (WHO-SAGE), a national survey of 11,046 participants aged 18 to 69 conducted in China in 2010. The key outcome was a dichotomous indicator of whether the respondent was taking hypertensive medication or other treatment. A series of logistic regression models were fitted to examine the research questions. Higher levels of social engagement were found to be associated with a lower odds of taking hypertensive medication or treatment, and the association was stronger for women than for men. Lifestyle factors (i.e. smoking and BMI) and perceived overall life satisfaction were significant covariates. Life satisfaction helped explain some of the social engagement benefit for both men and women and BMI only appeared to be a mediator for men. Being married was not significantly associated with lower odds of taking hypertensive medication or treatment in either men or women. Social engagement seems to be protective against hypertension for adult men and women in China, although causation could not be determined in this cross-sectional study. Psychosocial mechanisms are probably at work, but these vary by gender. PMID- 26669539 TI - Quantification of proteins using enhanced etching of Ag coated Au nanorods by the Cu(2+)/bicinchoninic acid pair with improved sensitivity. AB - Plasmonic nanosensors show great potential in ultrasensitive detection, especially with the plasmon peak position as the detection modality. Herein, a new sensitive but simple total protein quantification method termed the SPR-BCA assay is demonstrated by combining plasmonic nanosensors with protein oxidation by Cu(2+). The easy tuning of localized surface plasmon resonance (LSPR) features of plasmonic nanostructures makes them ideal sensing platforms. We found that the Cu(2+)/bicinchoninic acid (BCA) pair exhibits accelerated etching of Au@Ag nanorods and results in the LSPR peak shift. A linear relationship between Cu(2+) and the LSPR shift is found in a double logarithmic coordinate. Such double logarithm relationship is transferred to the concentration of proteins. Theoretical simulation shows that Au nanorods with large aspect ratios and small core sizes show high detection sensitivity. Via optimized sensor design, we achieved an increased sensitivity (the limit of detection was 3.4 ng ml(-1)) and a wide working range (0.5 to 1000 MUg ml(-1)) compared with the traditional BCA assay. The universal applicability of our method to various proteins further proves its potential in practical applications. PMID- 26669540 TI - The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers. AB - Each breast cancer has its unique spatial shape, but the clinical importance and the underlying mechanism for the three-dimensional tumor shapes are mostly unknown. We collected the data on the three-dimensional tumor size and tumor volume data of invasive breast cancers from 2,250 patients who underwent surgery between Jan 2000 and Jul 2007. The degree of tumor eccentricity was estimated by using the difference between the spheroid tumor volume and ellipsoid tumor volume (spheroid-ellipsoid discrepancy, SED). In 41 patients, transcriptome and exome sequencing data obtained. Estimation of more accurate tumor burden by calculating ellipsoid tumor volumes did not improve the outcome prediction when compared to the traditional longest diameter measurement. However, the spatial tumor eccentricity, which was measured by SED, showed significant variation between the molecular subtypes of breast cancer. Additionally, the degree of tumor eccentricity was associated with well-known prognostic factors of breast cancer such as tumor size and lymph node metastasis. Transcriptome data from 41 patients showed significant association between MMP13 and spatial tumor shapes. Network analysis and analysis of TCGA gene expression data suggest that MMP13 is regulated by ERBB2 and S100A7A. The present study validates the usefulness of the current tumor size method in determining tumor stages. Furthermore, we show that the tumors with high eccentricity are more likely to have aggressive tumor characteristics. Genes involved in the extracellular matrix remodeling can be candidate regulators of the spatial tumor shapes in breast cancer. PMID- 26669542 TI - Editorial: Digital Dentistry. PMID- 26669541 TI - 18F-FDG PET-Derived Textural Indices Reflect Tissue-Specific Uptake Pattern in Non-Small Cell Lung Cancer. AB - PURPOSE: Texture indices (TI) calculated from 18F-FDG PET tumor images show promise for predicting response to therapy and survival. Their calculation involves a resampling of standardized uptake values (SUV) within the tumor. This resampling can be performed differently and significantly impacts the TI values. Our aim was to investigate how the resampling approach affects the ability of TI to reflect tissue-specific pattern of metabolic activity. METHODS: 18F-FDG PET were acquired for 48 naive-treatment patients with non-small cell lung cancer and for a uniform phantom. We studied 7 TI, SUVmax and metabolic volume (MV) in the phantom, tumors and healthy tissue using the usual relative resampling (RR) method and an absolute resampling (AR) method. The differences in TI values between tissue types and cancer subtypes were investigated using Wilcoxon's tests. RESULTS: Most RR-based TI were highly correlated with MV for tumors less than 60 mL (Spearman correlation coefficient r between 0.74 and 1), while this correlation was reduced for AR-based TI (r between 0.06 and 0.27 except for RLNU where r = 0.91). Most AR-based TI were significantly different between tumor and healthy tissues (pvalues <0.01 for all 7 TI) and between cancer subtypes (pvalues<0.05 for 6 TI). Healthy tissue and adenocarcinomas exhibited more homogeneous texture than tumor tissue and squamous cell carcinomas respectively. CONCLUSION: TI computed using an AR method vary as a function of the tissue type and cancer subtype more than the TI involving the usual RR method. AR-based TI might be useful for tumor characterization. PMID- 26669543 TI - On the era of systematic reviews: Should we put our hands up? Should we choose a side? PMID- 26669544 TI - Dental implants with internal versus external connections: 1-year post-loading results from a pragmatic multicenter randomised controlled trial. AB - PURPOSE: To evaluate advantages and disadvantages of identical implants with internal or external connections. MATERIALS AND METHODS: Two hundred patients with any type of edentulism (single tooth, partial and total edentulism) requiring one implant-supported prosthesis were randomly allocated in two equal groups to receive either implants with an external connection (EC) or implants of the same type but with an internal connection (IC) (EZ Plus, MegaGen Implant, Gyeongbuk, South Korea) at seven centres. Due to slight differences in implant design/components, IC implants were platform switched while EC were not. Patients were followed for 1 year after initial loading. Outcome measures were prosthesis/implant failures, any complication, marginal bone level changes and clinician preference assessed by blinded outcome assessors. RESULTS: One hundred and two patients received 173 EC implants and 98 patients received 154 IC implants. Six patients dropped out with 11 EC implants and 3 patients with four IC implants, but all remaining patients were followed up to 1-year post-loading. Two centres did not provide any periapical radiographs. Two prostheses supported by EC implants and one supported by IC implants failed (P = 1.000, difference = 0.01, 95% CI: -0.05 to 0.04). Three EC implants failed in 3 patients versus two IC implants in 1 patient (P = 0.6227, difference = -0.02, 95% CI: -0.07 to 0.03). EC implants were affected by nine complications in 9 patients versus six complications of IC implants in 6 patients (P = 0.5988, difference = -0.02, 95% CI: -0.10 to 0.06). There were no statistically significant differences for prosthesis/implant failures and complications between the implant systems. One year after loading, there were no statistically significant differences in marginal bone level changes between the two groups (difference = 0.24, 95% CI: 0.01 to 0.50, P = 0.0629) and both groups lost bone from implant placement in a statistically significant manner: 0.98 mm for the EC implants and 0.85 mm for the IC implants. Five operators had no preference and two preferred IC implants. CONCLUSIONS: Within the limitations given by the difference in neck design and platform switching between EC and IC implants, preliminary short-term data (1 year post-loading) did not show any statistically significant differences between the two connection types, therefore clinicians could choose whichever one they preferred. PMID- 26669545 TI - Immediate loading of post-extractive versus delayed placed single implants in the anterior maxilla: outcome of a pragmatic multicenter randomised controlled trial 1-year after loading. AB - PURPOSE: To compare the effectiveness of immediate post-extractive single implants with delayed implants, placed in preserved sockets after 4 months of healing. Implants that achieved an insertion torque of at least 35 Ncm were immediately non-occlusally loaded. MATERIALS AND METHODS: Just after tooth extraction, and in the presence of less than 4 mm of vertical loss of the buccal bone in relation to the palatal wall, 106 patients requiring a single immediate post-extractive implant in the maxilla from second to second premolar were randomly allocated to immediate implant placement (immediate group; 54 patients) or to socket preservation using anorganic bovine bone covered by a resorbable collagen barrier (delayed group; 52 patients), according to a parallel group design at three different centres. Bone-to-implant gaps were to be filled with anorganic bovine bone, however this was not carried out in 17 patients (corresponding to 40% of those who should have been grafted). Four months after socket preservation, delayed implants were placed. Implants inserted with an insertion torque of at least 35 Ncm were immediately loaded with non-occluding provisional single crowns, then replaced after 4 months by definitive crowns. Patients were followed up to 1 year after loading. Outcome measures were implant failures, complications, aesthetics assessed using the pink esthetic score (PES), peri-implant marginal bone level changes and patient satisfaction recorded by blinded assessors. RESULTS: Nineteen (35%) implants were not immediately loaded in the immediate group versus 39 (75%) implants in the delayed placement group because an insertion torque superior to 35 Ncm could not be obtained. Six patients dropped out 4 months after loading from the delayed group versus none in the immediate group. Two implants failed in the immediate group (6%) versus none in the delayed group, with the difference showing no statistical significance (difference in proportions = 0.04; 95% CI: -0.03 to 0.11; P = 0.187). Eight minor complications occurred in the immediate group and one in the delayed group, and this was statistically significant (difference in proportions = 0.13; 95% CI: 0.03 to 0.23; P = 0.028). At delivery of definitive crowns, 4 months after loading, the mean aesthetic score was 12.8 and 12.6 in the immediate and delayed groups, respectively. At 1 year after loading, the mean aesthetic score was 13.0 and 12.8 in the immediate and delayed groups, respectively. There was no statistically significant difference at 4 months (P = 0.500) and at 1 year (P = 0.615). Marginal bone levels at implant insertion (after bone grafting) were 0.10 mm for immediate implants and 0.02 mm for delayed implants, which did not have a statistically significantly difference (mean difference = 0.08; 95% CI: 0.04 to 0.12; P < 0.001). One year after loading, patients of the immediate group lost on average 0.23 mm and those in the delayed group lost 0.29 mm, the difference being statistically significant (mean difference = -0.06; 95% CI: -0.11 to -0.01; P = 0.036). Patients of both groups were equally satisfied at 4 months as well as at 1 year after loading. CONCLUSIONS: There are more complications with immediate post-extractive implants in comparison to delayed implants. It seems more difficult to obtain an implant insertion torque superior to 35 Ncm in sockets preserved with anorganic bovine bone after a 4-month healing period than with postextractive sites. The aesthetic outcome appears to be similar for both groups. PMID- 26669546 TI - Immediate non-occlusal loading of immediate post-extractive versus delayed placement of single implants in preserved sockets of the anterior maxilla: 1-year post-loading outcome of a randomised controlled trial. AB - PURPOSE: To compare the effectiveness of immediate post-extractive single implants with delayed implants placed in preserved sockets after 4 months of healing. Implants that achieved an insertion torque of at least 35 Ncm were immediately non-occlusally loaded. MATERIALS AND METHODS: Just after tooth extraction, and in the presence of less than 4 mm of vertical loss of the buccal bone in relation to the palatal wall, 50 patients requiring a single immediate post-extractive implant in the maxilla from second to second premolar were randomly allocated for either immediate implant placement (immediate group; 25 patients) or for socket preservation using an algae-derived (phycogenic) bone substitute, covered by a resorbable collagen barrier (delayed group; 25 patients), according to a parallel group design in one centre. Bone-to-implant gaps were filled with an algae-derived bone substitute. Four months after socket preservation, delayed implants were placed. Implants inserted with an insertion torque of at least 35 Ncm were immediately loaded with non-occluding provisional single crowns, then replaced, after 4 months, by definitive crowns. Patients were followed up to 1 year after loading. Outcome measures were implant failures, complications, aesthetics assessed using the pink esthetic score (PES), peri implant marginal bone level changes and patient satisfaction, recorded by blinded assessors. RESULTS: Nine (36%) implants were not immediately loaded in the immediate group versus 19 (76%) implants in the delayed placement group, because an insertion torque superior to 35 Ncm could not be obtained, the difference being statistically significant (difference = - 0.40, 95% CI: -0.652 to -0.148, P = 0.010). Two patients dropped out 4 months after loading in the delayed group versus none in the immediate group. Two implants failed in the immediate group (8%) versus none in the delayed group, with the difference showing no statistical significance (considering 25 and 23 patients, the difference in proportions was 8% favouring the delayed group, 95% CI: -8.4 to 26.0, P = 0.490). Three minor complications occurred in the immediate group and two in the delayed group, and this was not statistically significant (considering 25 and 23 patients, the difference in proportions was 3.3% favouring the delayed group, 95% CI: -18.2 to 24.0, P = 1.000). At delivery of definitive crowns, 4 months after loading, the mean aesthetic score was 12.42 and 12.28 in the immediate and delayed groups, respectively. At 1 year after loading, the mean aesthetic score was 12.78 and 12.22 in the immediate and delayed groups, respectively. There were no statistically significant differences at 4 months (P = 0.666) and at 1 year (P = 0.090). Marginal bone levels at implant insertion (after bone grafting) were 0.01 mm for immediate and 0.06 mm for delayed implants, which showed a statistically significant difference (mean difference = - 0.04; 95% CI: -0.08 to -0.01; P = 0.009). One year after loading, patients of the immediate group lost on average 0.13 mm marginal bone and those in the delayed group lost 0.19 mm, however the difference was not statistically significant (mean difference = 0.05; 95% CI: 0.002 to 0.110; P = 0.06). All patients were fully satisfied, both for function and aesthetics, and would undergo the same procedure again at 4 months as well as at 1 year after loading. CONCLUSIONS: No significant differences were observed between the two procedures, although the only two implant failures were for immediate post-extractive implants. It seems more difficult to obtain an implant insertion torque superior to 35 Ncm in sockets preserved with algae-derived bone substitute after a 4-month healing period than at immediate post-extractive sites. PMID- 26669547 TI - Short implants as an alternative to crestal sinus lift: A 1-year multicentre randomised controlled trial. AB - PURPOSE: To evaluate the efficacy of short (5 or 6 mm-long) dental implants versus 10 mm or longer implants placed in crestally-lifted sinuses. MATERIALS AND METHODS: Twenty partially edentulous patients having 5 to 7 mm of residual crestal height and at least 7 mm thickness below the maxillary sinuses as measured on computerised tomography scans were randomised according to a parallel group design to receive either one to two 5 or 6 mm-long implants (10 patients) or 10 mm-long implants (10 patients) after crestal sinus lifting and grafting with anorganic bovine bone (Endobon). Implants were left to heal submerged for 4 months and loaded with reinforced acrylic provisional prostheses, and then replaced after 4 months, by definitive provisionally cemented or screw-retained metal-ceramic or metal-resin prostheses. Outcome measures were prosthesis and implant failures, any complications, radiographic peri-implant marginal bone level changes and patient's satisfaction assessed by blinded assessors, when possible. All patients were followed up to 1 year after loading. RESULTS: No patient dropped out, no failures or complications occurred. Short implants lost 0.70 +/- 0.19 mm of peri-implant marginal bone and long implants lost 0.87 +/- 0.21 mm of periimplant marginal bone 1 year after loading, the difference between the two groups showing no statistical significance (difference = -0.17 mm; 95% CI: -0.35 to 0.02; P = 0.078). CONCLUSIONS: Both techniques achieved excellent results and no differences were observed between prostheses supported by one to two implants, 5 to 6 mm-long or 10 mm-long in the posterior atrophic maxillae up to 1-year after loading, therefore it is up to the clinicians to decide which procedure to use, although longer follow-ups are needed to understand if one of these procedures could be more effective in the long-term. PMID- 26669548 TI - Immediately loaded machined versus rough surface dental implants in edentulous jaws: One-year postloading results of a pilot randomised controlled trial. AB - PURPOSE: To compare the effectiveness of immediately loaded total prostheses supported by implants with a roughened surface versus implants with a machined/turned surface. MATERIALS AND METHODS: Fifty edentulous or to-be rendered edentulous patients requiring an implant-supported cross-arch prosthesis, were randomised either to receive four to eight implants with a roughened surface (25 patients) or with a machined/turned surface (25 patients). Provisional metal-reinforced acrylic prostheses were delivered 48 h after implant placement. Provisional prostheses were replaced after 4 months, by definitive screw-retained metal-resin cross-arch restorations. Outcome measures were prosthesis and implant failures, any complications and peri-implant marginal bone level changes. Patients were followed 1 year after loading. RESULTS: One year after loading no patient dropped out. No prosthesis failed, but two machined implants were found to be mobile at definitive impression taking in 1 patient (Fisher's exact test: P = 0.312; difference in proportions = 4%; 95% Cl: -10 to 18). No complications occurred. Both groups presented a significant peri-implant marginal bone loss at 1 year after loading (P < 0.0001), -0.64 +/- 0.20 mm for rough implants and -0.68 +/- 0.23 mm for turned implants, respectively, with no statistically significant differences between the two groups (P = 0.482; mean difference = 0.04 mm; 95% Cl: -0.17 to 0.25). CONCLUSIONS: Up to 1 year after immediate loading, both implant surfaces provided good and similar results, however, the only two implants which failed early in the same patient had a machined surface. These preliminary results must be confirmed by larger trials with longer follow-ups. PMID- 26669549 TI - The Smile Esthetic Index (SEI): A method to measure the esthetics of the smile. An intra-rater and inter-rater agreement study. AB - PURPOSE: To propose a method to measure the esthetics of the smile and to report its validation by means of an intra-rater and inter-rater agreement analysis. MATERIALS AND METHODS: Ten variables were chosen as determinants for the esthetics of a smile: smile line and facial midline, tooth alignment, tooth deformity, tooth dischromy, gingival dischromy, gingival recession, gingival excess, gingival scars and diastema/missing papillae. One examiner consecutively selected seventy smile pictures, which were in the frontal view. Ten examiners, with different levels of clinical experience and specialties, applied the proposed assessment method twice on the selected pictures, independently and blindly. Intraclass correlation coefficient (ICC) and Fleiss' kappa) statistics were performed to analyse the intra-rater and inter-rater agreement. RESULTS: Considering the cumulative assessment of the Smile Esthetic Index (SEI), the ICC value for the inter-rater agreement of the 10 examiners was 0.62 (95% CI: 0.51 to 0.72), representing a substantial agreement. Intra-rater agreement ranged from 0.86 to 0.99. Inter-rater agreement (Fleiss' kappa statistics) calculated for each variable ranged from 0.17 to 0.75. CONCLUSION: The SEI was a reproducible method, to assess the esthetic component of the smile, useful for the diagnostic phase and for setting appropriate treatment plans. PMID- 26669551 TI - European Journal of Oral Implantology. Guidelines for authors. PMID- 26669550 TI - Dramatic course of osteomyelitis in a patient treated with immediately placed dental implants suffering from uncontrolled diabetes: A case report. AB - PURPOSE: To report a rare and dramatic complication following immediate dental implant placement in a heavy smoker, who had a delayed diagnosis of uncontrolled diabetes. MATERIALS AND METHODS: In this case report we present the dramatic course of a 64-year old female patient treated with five immediate post extractive dental implants in the mandible, who developed osteomyelitis, which manifested initially as local peri-implant inflammation and progressed into a spontaneous jaw fracture, despite repeated surgical interventions and antibiotic courses over a 3-year period, until diabetes was diagnosed. RESULTS: A symptom free status could be achieved only after partial mandibulectomy, treatment of diabetes and reconstruction with a microvascular fibula free flap. CONCLUSION: In the presence of mandibular osteomyelitis refractory to therapy, yet undiagnosed underlying pathologies, such as diabetes, should be investigated and treated urgently. PMID- 26669552 TI - Middle-range exploratory activity in adult rats suggests higher resilience to chronic social defeat. AB - OBJECTIVE: Stressful life events play an important role in the aetiology of human mood disorders and are frequently modelled by chronic social defeat (SD) in rodents. Exploratory phenotype in rats is a stable trait that is likely related to inter-individual differences in reactivity to stress. The aim of the study was to confirm that low levels of exploratory activity (LE) are, in rodents, a risk factor for passive stress coping, and to clarify the role of medium (ME) and high (HE) exploratory disposition in the sensitivity to SD. METHODS: We examined the effect of SD on male Wistar rats with LE, ME, and HE activity levels as measured in the exploration box. After SD, the rats were evaluated in social preference, elevated zero maze, and open-field tests. Brain tissue levels of monoamines were measured by high-performance liquid chromatography. RESULTS: Rats submitted to SD exhibited lower weight gain, higher sucrose consumption, showed larger stress induced hyperthermia, lower levels of homovanillic acid in the frontal cortex, and higher levels of noradrenaline in the amygdala and hippocampus. Open-field, elevated zero maze, and social preference tests revealed the interaction between stress and phenotype, as only LE-rats were further inhibited by SD. ME-rats exhibited the least reactivity to stress in terms of changes in body weight, stress-induced hyperthermia, and sucrose intake. CONCLUSION: Both low and high novelty-related activity, especially the former, are associated with elevated sensitivity to social stress. This study shows that both tails of a behavioural dimension can produce stress-related vulnerability. PMID- 26669553 TI - A molecular nanocap activated by superparamagnetic heating for externally stimulated cargo release. AB - A novel thermoresponsive snaptop for stimulated cargo release from superparamagnetic iron oxide core - mesoporous silica shell nanoparticles based on a [2 + 4] cycloreversion reaction (retro-Diels Alder reaction) is presented. The non-invasive external actuation through alternating magnetic fields makes this material a promising candidate for future applications in externally triggered drug delivery. PMID- 26669554 TI - Angioleiomyoma of the External Auditory Canal. PMID- 26669555 TI - Effects of Intralabyrinthine Hemorrhage on the Cochlear Elements: A Human Temporal Bone Study. AB - HYPOTHESIS: To compare histopathologic findings in the cochlea of human temporal bones with versus without intralabyrinthine hemorrhage. BACKGROUND: Hemorrhagic labyrinthitis can cause sensorineural damage, sudden hearing loss, and vertigo. Yet, to our knowledge, no studies have quantitatively described histopathologic effects of intralabyrinthine hemorrhage on the elements of the cochlea. METHODS: We analyzed 46 human temporal bone samples from 23 patients with unilateral intralabyrinthine hemorrhage (23 samples from ears with intralabyrinthine hemorrhage and 23 samples from contralateral ears without). We noted the location of hemorrhage in the inner ear, the degree of endolymphatic hydrops, the number of spiral ganglion cells and hair cells, mean loss of fibrocytes in spiral ligament, and areas of the stria vascularis and spiral ligament. RESULTS: Intralabyrinthine hemorrhage caused significant loss of outer hair cells in the lower basal (p = 0.001), upper basal (p = 0.005), and lower middle (p = 0.012) cochlear turns. The degree of endolymphatic hydrops was significantly different between the hemorrhagic and contralateral sides (p = 0.011). But we found no significant difference between the 2 sides in the number of inner hair cells, spiral ganglion cells, and fibrocytes, or in the areas of the stria vascularis and spiral ligament between the two groups (p > 0.05). CONCLUSION: These findings suggest that such patients could be good candidates for hearing aid or cochlear implant if they have profound sensorineural hearing loss. PMID- 26669556 TI - Transcanal Micro-Osteotome Only Technique for Excision of Exostoses. AB - OBJECTIVES: To evaluate the outcomes and complications of transcanal excision of exostoses using micro-osteotomes, without a postauricular incision or the use of the drill. STUDY DESIGN: A retrospective chart review of patients undergoing exostoses excision. SETTING: Tertiary Care Medical Center. SUBJECTS AND METHODS: All of the patients underwent surgical removal of the exostoses using only a 1 or 2 mm micro-osteotomes. Patients were followed postoperatively and associated complications were evaluated. RESULTS: One-hundred thirty-eight ears in 106 patients were treated for obstructive exostosis. The average age of patients was 43 +/- 16 years. Of these, 99 were man (93%) and 7 were woman (7%). A majority of the patients (84%, n = 89) had 90 to 100% obstruction of the ear canal. Complete ear canal healing was observed in 80% of patients by 3 weeks. All but one patient had healed by 6 weeks postoperatively. There were 9 (6.5%) slit tympanic membrane perforations that healed with intraoperative gelfoam or fascia myringoplasty. One patient had an anterior canal mobilization which required Xeroform packing for 3 weeks for stabilization. There were no postoperative vertigo, facial paresis, conductive/sensorineural hearing loss, soft tissue stenoses, and no skin grafting required. CONCLUSIONS: This is the first study to report a series of patients performing solely a transcanal approach using micro-osteotomes for removing exostoses. Results indicate that it is a safe procedure with low complication rate and expeditious healing. Patients with 100% obstruction can have this procedure performed with no significant increase in morbidity. PMID- 26669557 TI - Deeper Cochlear Implant Electrode Insertion Angle Improves Detection of Musical Sound Quality Deterioration Related to Bass Frequency Removal. AB - BACKGROUND: Cochlear implant (CI) electrode arrays typically do not reach the most apical regions of the cochlea that intrinsically encode low frequencies. This may contribute to diminished implant-mediated musical sound quality perception. The objective of this study was to assess the effect of varying degrees of apical cochlear stimulation (measured by angular insertion depth) on musical sound quality discrimination. HYPOTHESIS: Increased apical cochlear stimulation will improve low-frequency perception and musical sound quality discrimination. METHODS: Standard (31.5 mm, n = 17) and medium (24 mm, n = 8) array Med-EL CI users, and normal hearing (NH) listeners (n = 16) participated. Imaging confirmed angular insertion depth. Participants completed a musical discrimination task in which they listened to a real-world musical stimulus (labeled reference) and provided sound quality ratings to versions of the reference, which included a hidden reference and test stimuli with increasing amounts of low-frequency removal. Scores for each CI users were calculated on the basis of how much their ratings differed from NH listeners for each stimulus version. RESULTS: Medium array and standard users had significantly different insertion depths (389.4 +/- 64.5 and 583.9 +/- 78.5 degrees, respectively; p < .001). A significant Pearson's correlation was observed between angular insertion depth and the hidden reference scores (p < 0.05). CONCLUSION: CI users with greater apical stimulation made sound quality discriminations that more closely resembled those of NH controls for stimuli that contained low frequencies (< 200 Hz of information). These findings suggest that increased apical cochlear stimulation improves musical low-frequency perception, which may provide a more satisfactory music listening experience for CI users. PMID- 26669558 TI - Utilization of Benchtop Next Generation Sequencing Platforms Ion Torrent PGM and MiSeq in Noninvasive Prenatal Testing for Chromosome 21 Trisomy and Testing of Impact of In Silico and Physical Size Selection on Its Analytical Performance. AB - OBJECTIVES: The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. METHODS: Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied. RESULTS: Using a z score value of 3 as the cut-off, 98.11%-100% (104-106/106) specificity and 100% (24/24) sensitivity and 99.06%-100% (105-106/106) specificity and 100% (24/24) sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantly--p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively. CONCLUSIONS: Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on high-to-ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide. PMID- 26669559 TI - Order and Chaos in the World of Serrated Polyps: Using Oriented Specimens to Help Disoriented Pathologists. PMID- 26669560 TI - Fecal Impaction in the Emergency Department: An Analysis of Frequency and Associated Charges in 2011. AB - GOALS: The aim of this study was to analyze the incidence and associated charges of fecal impaction for trends in hospital and patient demographics in emergency departments (ED) across the United States. BACKGROUND: In 2010, an ICD-9-CM code (560.32) for fecal impaction was introduced, allowing for assessment of fecal impaction incidence. STUDY: Data were obtained from the National Emergency Department Sample records in which fecal impaction (ICD-9-CM code 560.32) was first listed as a diagnosis in 2011. RESULTS: In 2011, there were 42,481 [95% confidence interval (CI), 39,908-45,054] fecal impaction ED visits, with an overall rate of 32 fecal impaction visits per 100,000 ED visits. Adjusted for inflation in 2014 dollars, the associated mean charge of a fecal impaction ED visit was $3060.47 (95% CI, $2943.02-$3177.92), with an aggregate national charge in the US of $130,010,772 (95% CI, $120,688,659-$139,332,885). All charges were adjusted for inflation and reported in 2014 dollars. Late elders (85+ y) had the highest rate of fecal impaction ED visits, followed by early elders (65 to 84 y). Medicare was the primary payer for the greatest number of fecal impaction ED visits accounting for nearly two thirds of visit payments. CONCLUSION: This study reports previously unexplored statistics on the number, frequency, and associated charges of ED visits with a primary diagnosis of fecal impaction, a condition found most commonly among elders. PMID- 26669561 TI - Synthesis of aromatic ruthenabenzothiophenes via C-H activation of thiophenes. AB - The first ruthenabenzothiophenes have been achieved via the C-H activation of thiophene. These species feature high thermal stability and resistance of a moderate oxidant, which constitute valuable addition to the rare metallaaromatic containing second-row transition metals. PMID- 26669562 TI - The Neutrophil-to-Lymphocyte Ratio before Repeat Prostate Needle Biopsy for Predicting Prostate Cancer. PMID- 26669563 TI - Early Hemodynamic Changes during Head-Up Tilt Table Testing Can Predict a Neurocardiogenic Response in an African-American Patient Population. AB - BACKGROUND: Head-up tilt table testing (HUTT) is time-consuming and associated with increased patient morbidity. Hemodynamic changes that occur during the early phase of HUTT may be predictive of neurocardiogenic syncope. METHODS: A retrospective chart review was performed in 119 consecutive African Americans ( 57 +/- 19) who underwent HUTT for evaluation of syncope of unknown etiology. Positive responses were defined as the development of symptoms linked with a systolic blood pressure (BP) <90 mm Hg, heart rate <50 b.p.m. or sinus arrest >3 s. Hemodynamic variables during the passive phase of HUTT were analyzed and results were then classified as a function of various predictors. RESULTS: Sixty two subjects (52%) had positive HUTT, and 57 (48%) had negative HUTT. Early changes in BP variables from baseline significantly predicted HUTT responses (p < 0.05). There was also a significant interaction between age and BP. An algorithm based on age and BP was developed which had positive and negative predictive values of 67.7 and 93%, respectively, with an accuracy of 79.8%. CONCLUSION: A novel algorithm utilizing the patients' age and changes in both systolic and diastolic BP during the early phase of HUTT enables the prediction of HUTT results without the use of vasoactive stimulation, allowing for rapid diagnosis, decreased patient morbidity and reduction in costs. PMID- 26669564 TI - Case Report: Spontaneous Iliac Intramuscular Bleed After Orthotopic Heart Transplant. AB - This case report describes an unusual case of spontaneous iliac intramuscular hematoma after a heart transplant secondary to valvular cardiomyopathy. A spontaneous retroperitoneal hematoma occurring after a heart transplant is rare, but can occur when the patient is on immunosuppressive medications. This could be secondary to the medications' ability to suppress the immune system and cause antiplatelet therapylike effects. Spontaneous retroperitoneal hematomas can cause significant patient morbidity, sometimes even causing immobility; however, a high index of suspicion with early recognition and immediate intervention can reduce the sequelae. Although the occurrence of a spontaneous retroperitoneal hematoma after a heart transplant is rare; there should be a high index of suspicion in cases where the patient is elderly, has experienced rejection episodes, and is taking immunosuppressants, or in cases where the patient is additionally on anticoagulation and antiplatelet therapy. PMID- 26669565 TI - Antioxidant activity and protection against oxidative-induced damage of Acacia shaffneri and Acacia farnesiana pods extracts: in vitro and in vivo assays. AB - BACKGROUND: Obesity is a worldwide public health issue, reaching epidemic condition in developing countries associated to chronic diseases. Oxidative damage is another side effect of obesity. Antioxidant activity from plant components regulates at some extent this imbalance. Main goal of the present study was to determine the antioxidant activity and protection against oxidative induced damage of Acacia shaffneri (AS) and Acacia farnesiana (AF) pods extracts. METHODS: To evaluated antioxidant activity and radical scavenging capacity of AS and AF extracts, two experiments were performed: 1) pods extracts were challenged against H2O2 using kidney cells in an in vitro assay; and 2) (Meriones unguiculatus) was employed in an in vivo assay to observe the effect of pods extracts on scavenging properties in plasma. RESULTS: Both pods extracts presented an important protective effect on radical scavenging capacity against ABTS* + and DPPH(+), and also in TBARS formation in vitro. Vegetal pods extracts did not induce any pro-oxidative effect when added to kidney cells in DMEM. Cells damage in DMEM with addition of H2O2 was significantly higher than those when vegetal pods extracts were added at 50 (P < 0.05) or 200 ppm (P < 0.001). Plasma scavenging properties presented an important dose-dependent positive effect in those groups where pods extracts were administered. CONCLUSIONS: The antioxidant protection of the acacia pods extracts reported in this study suggests the possible transference of antioxidant components and protective effects to animal products (milk, meat, and by-products) from Acacia pods when this vegetation is included in the diet. In order to evaluate, the possible transference of theirs antioxidant components to animal products, the incorporation of these non conventional resources to ruminant feeding is a good opportunity of study. Profiling of Acacia farnesiana pods extract is necessary to identify the responsible bioactive compounds of protective properties. PMID- 26669566 TI - Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib). METHODS: A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods. RESULTS: The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively. CONCLUSIONS: In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA. PMID- 26669567 TI - Development of a mono-promoter-driven CRISPR/Cas9 system in mammalian cells. AB - The CRISPR/Cas9 system has been used for spatio-temporal gene modification through the ubiquitous expression of gRNA by an RNA polymerase III promoter and the controlled expression of Cas9 using a tissue-specific or inducible promoter. However, unexpected gene disruptions indicate the necessity of a tissue-specific or inducible expression of not only Cas9 but also gRNA. In the present study, we attempted to develop a CRISPR/Cas9 system that could express functional gRNAs and Cas9 by a single RNA polymerase II promoter and induce multi-loci disruptions in specific cells. To this end, we designed vectors expressing ribozyme-flanked gRNAs (RGRs) and Cas9 mRNAs simultaneously. We showed that the mono-promoter driven vector induces gene disruptions at the target loci in HEK 293 cells after transfection. In addition, two target loci were disrupted simultaneously by the transfection of a mono-promoter-driven vector expressing two RGRs and Cas9 mRNA. Finally, we constructed a universal vector for use in the construction of plasmids to be applied to the present mono-promoter-driven CRISPR/Cas9 system. We have thus provided a versatile tool for generating gene disruptions by the CRISPR/Cas9 system; this system should contribute to a wide range of investigations, including studies on spatio-temporal gene functions. PMID- 26669568 TI - Stents in patients with esophageal cancer before chemoradiotherapy: high risk of complications and no impact on the nutritional status. AB - Preoperative chemoradiotherapy is the standard of care for locally advanced esophageal cancer, causing persistent deterioration in the nutritional status. We performed a prospective study to evaluate the safety and efficacy of esophageal double-covered self-expandable metal stents in patients with esophageal cancer before chemoradiotherapy. The nutritional status and dysphagia were prospectively recorded. Eleven patients were included: eight were moderate and three were severely malnourished. After stent placement, dysphagia improved in all patients. With regard to complications, one patient developed an esophageal perforation that required urgent esophagectomy. Four patients presented stent migration. Three of these patients required enteral nutrition and none was submitted to surgery because of poor nutritional status. Of the other six patients, only four were operated upon. Stent placement presented a high complication rate and did not prevent weight loss or malnutrition. Other alternatives, including naso gastric tube placement or endoscopic percutaneous gastrostomy or jejunostomy, should be considered. PMID- 26669569 TI - Sarcopenia and length of hospital stay. AB - BACKGROUND/OBJECTIVES: We aimed to quantify the association of sarcopenia with length of hospital stay (LOS) and to identify factors associated with sarcopenia among hospitalized patients. SUBJECTS/METHODS: A total of 655 patients composed the study sample. A longitudinal study was conducted in a University Hospital. Sarcopenia was defined, according to European Consensus criteria, as low muscle mass (bioelectrical impedance analysis) and low muscle function (handgrip strength). Logistic regression, Kaplan-Meier and Cox adjusted proportional hazards methods were used. LOS was determined from the date of hospital admission and discharge home (event of interest). RESULTS: Participants were aged 18 to 90 years (24.3% sarcopenic). Factors associated with sarcopenia were male gender, age ?65 years, moderate or severe dependence, undernutrition and being admitted to a medical ward. Sarcopenic patients presented a lower probability of being discharged home (hazard ratio (HR), 95% confidence interval (CI)=0.71, 0.58 0.86). However, after stratifying for age groups, this effect was visible only in patients aged <65 years (HR, 95% CI= 0.66, 0.51-0.86). Moreover, sarcopenic overweight or obese patients presented a higher probability of being discharged home (HR, 95% CI=0.78, 0.61-0.99) than nonoverweight sarcopenic patients (HR, 95% CI=0.63, 0.48-0.83). CONCLUSIONS: Being male, age ?65 years, presenting dependence, being undernourished and admitted to a medical ward were factors associated with sarcopenia among hospitalized adult patients. Sarcopenia is independently associated with longer LOS, although this association is stronger for patients aged <65 years. Moreover, sarcopenic overweight was associated with a higher probability of discharge home than nonoverweight sarcopenia. PMID- 26669571 TI - Dietary under-reporting: what foods and which meals are typically under-reported? AB - Little objective information exists regarding which foods and meals are typically under-reported during retrospective self-reported dietary assessments. Automated wearable cameras record dietary behaviours in free-living settings and allow the context of under-reporting to be explored. As part of a study to validate image assisted dietary assessment, 40 participants wore a wearable camera on days before three image-assisted 24-h dietary recalls. The foods and meals were typically under-reported, and the environmental and social contexts of under reporting were assessed. Under-reporting occurred most frequently during afternoon snacks (75/265 foods), dinner (54/265 foods) and breakfast (44/265 foods). Snack foods were most frequently unreported during afternoon snacks, and condiments were most frequently under-reported at breakfasts. No clear pattern of social or environmental contexts for under-reporting was observed. Wearable cameras can identify when specific foods are likely to be under-reported during retrospective dietary assessments. Problematic foods and meals identified could be given additional attention during dietary assessments. PMID- 26669572 TI - An assessment of the potential health impacts of food reformulation. AB - BACKGROUND/OBJECTIVES: Policies focused on food quality are intended to facilitate healthy choices by consumers, even those who are not fully informed about the links between food consumption and health. The goal of this paper is to evaluate the potential impact of such a food reformulation scenario on health outcomes. SUBJECTS/METHODS: We first created reformulation scenarios adapted to the French characteristics of foods. After computing the changes in the nutrient intakes of representative consumers, we determined the health effects of these changes. To do so, we used the DIETRON health assessment model, which calculates the number of deaths avoided by changes in food and nutrient intakes. RESULTS: Depending on the reformulation scenario, the total impact of reformulation varies between 2408 and 3597 avoided deaths per year, which amounts to a 3.7-5.5% reduction in mortality linked to diseases considered in the DIETRON model. The impacts are much higher for men than for women and much higher for low-income categories than for high-income categories. These differences result from the differences in consumption patterns and initial disease prevalence among the various income categories. CONCLUSIONS: Even without any changes in consumers' behaviors, realistic food reformulation may have significant health outcomes. PMID- 26669570 TI - The effect of dietary counselling on food intakes in pregnant women at risk for gestational diabetes: a secondary analysis of a randomised controlled trial RADIEL. AB - BACKGROUND/OBJECTIVES: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM may be prevented by improving the diets of pregnant women. The objective of this study was to evaluate the effect of dietary counselling on the diets of pregnant women at GDM risk. SUBJECTS/METHODS: This study was a secondary analysis of a randomised controlled trial the Finnish gestational diabetes prevention study (RADIEL) in which pre-pregnant and pregnant women with previous GDM or BMI ?30 kg/m(2) were allocated into two groups, namely the control and the intervention groups. The control group received standard antenatal dietary counselling according to the Finnish Nutrition Recommendations. The intervention group participated in one individual dietary counselling session and one group dietary counselling session in addition to the standard counselling. This study included women who were recruited during pregnancy. To assess changes in food intake, food-intake questionnaires were collected during the first and the second trimester of pregnancy. Bootstrap type analysis of covariance was used, and 242 participants were included in the final analysis to study changes in food intake. RESULTS: The intakes of low-fat cheese (baseline adjusted mean 0.09 times/day; 95% confidence interval (CI) 0.07, 0.24; P=0.040) and fish (baseline adjusted mean 0.28 times per week; 95% CI 0.08, 0.49; P=0.011) showed a significant increase in the intervention group compared with the control group. CONCLUSIONS: This study showed that dietary counselling in early pregnancy can lead to modest dietary improvements in pregnant women at GDM risk. PMID- 26669573 TI - Fluid consumption, total water intake and first morning urine osmolality in Spanish adolescents from Zaragoza: data from the HELENA study. AB - BACKGROUND/OBJECTIVES: The objective of the study is to describe the hydration status and to assess the main food- and/or fluid intake-associated factors in healthy adolescents. SUBJECTS/METHODS: A total of 194 adolescents from the city of Zaragoza aged 12.5-17.5 years (99 males) participating in the 'Healthy Lifestyle in Europe by Nutrition in Adolescence' (HELENA) cross-sectional study were included. First morning urine was collected, and osmolality was determined by freezing point depression osmometer. A self-reported computer-based 24-h dietary recall was applied the same day of the urine collection. Analysis of variance, Kruskal-Wallis procedure or Pearson's chi(2) analyses was used to examine the group associations. RESULTS: Seventy-one percent of adolescents did not meet the European Food Safety Agency (EFSA) recommendations for average total water intake (TWI), and 68% had high first morning urine osmolality values. TWI and the proportion of those meeting EFSA reference values significantly (P<0.05) decreased with increased osmolality. Males who met the EFSA recommendations consumed significantly (P<0.05) more plain water (1035.13 vs 582.68 ml) and dairy drinks (368.13 vs 226.68 ml) than those who did not. In females, the consumption of water (1359.41 vs 620.44 ml) and sugar-sweetened beverages (214.61 vs 127.42 ml) was significantly higher in those meeting the EFSA recommendations than in those who did not. First morning urine osmolality was associated with vegetables (unstandardized beta: -0.6; 95% confidence interval (CI): -1.02 and -0.18) and fruits intake (beta: -0.41; 95% CI: -0.63 and -0.19) in males and with dairy drinks (beta: -0.39; 95% CI: -0.76 and -0.02) and fruits (beta: -0.41; 95% CI: 0.73 and -0.10) in females. CONCLUSIONS: There was a high prevalence of inadequate TWI and high urine osmolality among these Spanish adolescents. Lower urine osmolality was associated with higher consumption of vegetables in males, dairy drinks in females and fruits in both males and females. PMID- 26669574 TI - Diagnostic performance of body mass index to identify adiposity in women. AB - BACKGROUND/OBJECTIVES: The aim of this study was to determine the diagnostic performance of body mass index (BMI) and to detect the optimal BMI cutoff points to define adiposity in women of various ages. SUBJECTS/METHODS: A total of 2409 women participated. Fat mass was measured using a multifrequency bioelectrical impedance analysis. The diagnostic performance of BMI to identify adiposity was evaluated using a fat mass percentage cutoff point of ?35%. RESULTS: Although 40% of women were overfat, the BMI-based obesity prevalence was 21%. In the total sample, BMI had low overall performance, which resulted in a sensitivity of 51.9% (95% confidence interval (CI): 48.7-55.2%) and a specificity of 99.2% (95% CI: 98.7-99.6%). BMI failed to identify overfat women with intermediate BMI ranges. An analysis of the receiver operating characteristic curves of all of the subjects demonstrated that optimal cutoff point corresponded to a BMI value of 26.4 kg/m(2). The diagnostic performance of BMI did not differ as age increased. CONCLUSIONS: BMI has a high specificity but a low sensitivity to detect adiposity, and it fails to identify nearly half of women with excess fat mass. We provide evidence that a commonly used BMI cutoff value to diagnose obesity is too high among women. PMID- 26669575 TI - Parallel charge sheets of electron liquid and gas in La0.5Sr0.5TiO3/SrTiO3 heterostructures. AB - We show here a new phenomenon in La0.5Sr0.5TiO3/SrTiO3 (LSTO/STO) heterostructures; that is a coexistence of three-dimensional electron liquid (3DEL) and 2D electron gas (2DEG), separated by an intervening insulating LSTO layer. The two types of carriers were revealed through multi-channel analysis of the evolution of nonlinear Hall effect as a function of film thickness, temperature and back gate voltage. We demonstrate that the 3D electron originates from La doping in LSTO film and the 2D electron at the surface of STO is due to the polar field in the intervening insulating layer. As the film thickness is reduced below a critical thickness of 6 unit cells (uc), an abrupt metal-to insulator transition (MIT) occurs without an intermediate semiconducting state. The properties of the LSTO layer grown on different substrates suggest that the insulating phase of the intervening layer is a result of interface strain induced by the lattice mismatch between the film and substrate. Further, by fitting the magnetoresistance (MR) curves, the 6 unit cell thick LSTO is shown to exhibit spin-orbital coupling. These observations point to new functionalities, in addition to magnetism and superconductivity in STO-based systems, which could be exploited in a multifunctional context. PMID- 26669576 TI - Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits. AB - Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrP(Sc)). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrP(Sc). In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmol/nmol protein) than three other flavonoid derivatives (flavone, chalcone, and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrP(Sc)-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiography experiments demonstrated high accumulation of [(125)I]SC-OMe and [(125)I]SC-(OMe)2 in prion deposit-rich regions of the mBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that [(123)I]SC-OMe showed consistent brain distribution with the presence of PrP(Sc) deposits in the mBSE-infected mice brain. In conclusion, [(123)I]SC-OMe appears a promising SPECT radioligand for monitoring prion deposit levels in the living brain. PMID- 26669577 TI - High performance polymer tandem solar cell. AB - A power conversion efficiency of 9.02% is obtained for a fully solution-processed polymer tandem solar cell, based on the diketopyrrolopyrrole unit polymer as a low bandgap photoactive material in the rear subcell, in conjunction with a new robust interconnecting layer. This interconnecting layer is optically transparent, electrically conductive, and physically strong, thus, the charges can be collected and recombined in the interconnecting layer under illumination, while the charge is generated and extracted under dark conditions. This indicates that careful interface engineering of the charge-carrier transport layer is a useful approach to further improve the performance of polymer tandem solar cells. PMID- 26669578 TI - Excitation Spectra of Nucleobases with Multiconfigurational Density Functional Theory. AB - Range-separated hybrid methods between wave function theory and density functional theory (DFT) can provide high-accuracy results, while correcting some of the inherent flaws of both the underlying wave function theory and DFT. We here assess the accuracy for excitation energies of the nucleobases thymine, uracil, cytosine, and adenine, using a hybrid between complete active space self consistent field (CASSCF) and DFT methods. The method is based on range separation, thereby avoiding all double-counting of electron correlation and is denoted long-range CASSCF short-range DFT (CAS-srDFT). Using a linear response extension of CAS-srDFT, we compare the first 7-8 excited states of the nucleobases with perturbative multireference approaches as well as coupled cluster based methods. Our results show that the CAS-srDFT method can provide accurate excitation energies in good correspondence with the computationally more expensive methods. PMID- 26669579 TI - [Direct Drive Simulation - Sound-Simulation of the Vibrant Soundbridge(r)]. AB - BACKGROUND: The Direct-Drive-Simulation (DDS) tends to simulate the sound quality of hearing with the active middle ear implant Vibrant Soundbridge((r)) (VSB). Up to now a scientific evaluation of the validity is missing. Furthermore, the test procedure has not been described yet. Aim of this study was to evaluate the test validity and to describe the test realization in detail. MATERIAL AND METHODS: 10 patients evaluated their sound impression on scales from 1 to 10 concerning sound quality during DDS, postoperative free field testing at least 3 month after the first fitting of the VSB and in the everyday life situation. 3 patients were implanted bilaterally. Together, 36 data sets could be analyzed. RESULTS: Coupling of the Floating Mass Transducer (FMT), which was placed inside of a silicone probe during DDS was successful in all cases. In 11 out of 13 cases the coupling quality was judged as "good" an only in 2 cases as "medium". None of the patients needed local anesthesia. Comparing the evaluation of the sound impression during DDS preoperatively, and with the implanted VSB in free field testing and in everyday life no significant differences were found. CONCLUSION: The DDS offers the possibility of a realistic preoperative sound simulation of the "VSB-hearing" in case of sensorineural hearing loss. Thus, the test is supposed to facilitate the patient's decision towards possible treatment options. The specialist gets additional information regarding the indication especially when audiologic indication criteria are critical. The DDS should be a basic part of the preoperative diagnostic prior to VSB-implantation. PMID- 26669580 TI - [FEES in Infants with Swallowing Disorders - A Feasible Procedure?]. AB - BACKGROUND: Although FEES has been established as a valid procedure in instrumental evaluation of swallowing even in young children, the significance of the endoscopic method on infants has not yet been fully clarified. The aim of this prospective study was to evaluate fiberoptic endoscopic examination of swallowing in infants by focusing on its feasibility and limits. PATIENTS AND METHODS: From 11/2011 to 3/2015 27 infants from a neuropediatric hospital presented for fiberoptic endoscopic examination of swallowing. Compared with Langmore standard FEES was carried out in a modified algorithm. RESULTS: In 24 of the 27 infants information about swallowing pathology could be obtained. Silent aspiration of saliva (Penetration Aspiration Scale (PAS) level 8) or silent deep penetration of test diets to the level of the glottis (PAS level 5) presented in 10 children and overt deep penetration of test diets in 3 children. In no case a sufficient insight into the subglottis or trachea could be obtained. Therefore a differentiation of silent deep penetration and aspiration of test diets was impossible. As a consequence of the FEES results, probe and diet management was changed in 7 children. CONCLUSIONS: In this study fiberoptic endoscopic evaluation of swallowing in a modified algorithm turned out to be a feasible tool for the diagnostics of swallowing disorders in about 89 percent of the infants. The procedure was limited in terms of providing direct evidence on aspiration in cases of deep penetrations of test diets. PMID- 26669581 TI - [Evaluation and Optimization of Microvascular Arterial Anastomoses by Transit Time Flow Measurement]. AB - INDRODUCTION: The regular application of transit time flow measurement in microvascular anastomoses during heart surgery has lead to improvements of the outcome of coronary artery bypass grafts. Our study was meant to discover whether this measurement method was also applicable for evaluation and optimization of microvascular arterial anastomoses of radial forearm flaps. METHODS: In this prospective examination a combining ultrasound imaging and transit time flow measurement device (VeriQ, MediStim) was used during surgery to assess anastomotic quality of 15 radial forearm flaps. Pulsatility index (PI) and mean blood flow were measured immediately after opening the arterial anastomosis as well as 15 min afterwards. Furthermore, application time and description of handling were recorded seperately for every assessment. RESULTS: Mean blood flow immediately after opening the anastomosis and 15 min later were 3.9 and 3.4 ml/min resepectively showing no statistically significant difference (p=0.96). There was no significance in the increase of pulsatility index from 22.1 to 27.2 (p=0.09) during the same time range, either. Due to measurement results showing atypical pulse curves in 2 cases decision for surgical revision of the anastomoses was made. All forearm flaps showed good vascularisation during follow up. Time for device set up, probe placement and measurements was about 20 min. Handling was described to be uncomplicated without exception. There were no noteworthy problems. CONCLUSION: Transit time flow measurement contributes to the improvement of anastomotic quality and therefore to the overall outcome of radial forearm flaps. The examined measurement method provides objective results and is useful for documentation purposes. PMID- 26669582 TI - [Inpatient Salivary Gland Surgery in Germany: A DRG-Based Nationwide Analysis, 2007-2011]. AB - BACKGROUND: This is the first population-based analysis of inpatient salivary gland surgery across Germany. METHODS: Nationwide Diagnosis-Related Groups (DRG) statistics for 2007 to 2011 were analyzed regarding indications for salivary gland surgery based on ICD-10 codes. Age specific surgery rates were calculated for both sexes. RESULTS: Inpatient salivary gland surgical rates in 2007-2011 amounted for incisions (OPS [Classification of Operations and Procedures] code 5 260) 1.43 per 100 000 population, for excisions (5-261) 2.06 per 100 000, for salivary gland resections (5-262) 2.06 per 100 000, and for external incisions (5 270) 0.43 per 100 000. Regarding the mentioned four OPS codes, the surgical rates for benign tumors accounted to 10.08 per 100 000, for sialadenitis (without sialoliths) to 4.00 per 100 000, for malignant tumors to 3.90 per 100 000, and for sialolithiasis to 2.09 per 100 000. The increase of surgical rates from 2007 to 2011 was significant for malignant and benign tumors as well as for salivary stones. The surgical rates were highest for patients>60 years. DISCUSSION: Especially surgery for malignant tumors was more frequent than expected. In spite of the introduction of minimal invasive technique the rates for salivary gland resections in case of sialadenitis or sialolithiasis still seem to be high. PMID- 26669583 TI - Documentation Status as a Contextual Determinant of HIV Risk Among Young Transgender Latinas. AB - PURPOSE: The purpose of this study was to explore the contextual factors that determine or mitigate vulnerability to HIV among Latina transgender women. Documentation status (legal authorization to live in the United States) has been cited by other studies as a barrier to recruitment or engagement in HIV-related care among immigrant Latinos, but not explored as a determinant of HIV risk for transgender immigrant Latinas. METHODS: We collaborated with a community-based organization to explore these contextual, including social and structural, factors. In-depth interviews in Spanish captured life histories of eight 18- to 29-year-old transgender Latinas, who collectively self-identify as chicas trans. Codes were assigned deductively from the interview guide, and emerging themes were identified throughout data collection. RESULTS: Most participants migrated to the United States from Central America after experiencing discrimination and violence in their countries of origin. Participants emphasized documentation status as a critical factor in three areas related to social and structural determinants of HIV risk: gender identity expression, access to services, and relationship power dynamics. Chicas trans who gained legal asylum reported greater control over sexual relationships, improved access to services, and less risky employment. CONCLUSIONS: Documentation status emerged as a key HIV risk factor for this population. For undocumented transgender Latinas, legal asylum appears to be a promising HIV-related protective factor. Further research could assess whether legal assistance combined with wraparound support services affects HIV prevention for this population. PMID- 26669584 TI - Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis. Short- and Long-Term Outcomes. AB - RATIONALE: Patients with advanced lung disease due to systemic sclerosis have long been considered suboptimal and often unacceptable candidates for lung transplant. OBJECTIVES: To examine post-lung transplant survival of patients with systemic sclerosis compared with patients with pulmonary fibrosis and to identify risk factors for 1-year mortality. METHODS: In a retrospective cohort study, we compared post-lung transplant outcomes of 72 patients with scleroderma with those of 311 patients with pulmonary fibrosis between June 2005 and September 2013 at our institution. Actuarial survival estimates were calculated using Kaplan-Meier curves. In Cox regression models, we determined risk factors for post-transplant mortality, controlling for whether patients had scleroderma or pulmonary fibrosis. MEASUREMENTS AND MAIN RESULTS: Post-transplant survival did not differ significantly between scleroderma and pulmonary fibrosis at year 1 (81% scleroderma vs. 79% pulmonary fibrosis; P = 0.743), at year 5 conditional on 1 year survival (66% vs. 58%; P = 0.249), or overall (P = 0.385). In multivariate analysis, body mass index greater than or equal to 35 kg/m(2) predicted poor 1 year survival in pulmonary fibrosis (hazard ratio, 2.76; P = 0.003). Acute cellular rejection-free survival did not differ significantly between the scleroderma and pulmonary fibrosis cohorts. Patients with scleroderma had significantly better bronchiolitis obliterans syndrome stage 1 or higher-free survival than did patients with pulmonary fibrosis. CONCLUSIONS: Our findings that 1- and 5-year survival rates of patients with scleroderma were similar to those of patients with pulmonary fibrosis indicate that lung transplant is a reasonable treatment option in selected patients with scleroderma. PMID- 26669585 TI - Ibuprofen-induced acute interstitial nephritis in the paediatric population. PMID- 26669586 TI - Perceived organizational support and intention to remain: The mediating roles of career success and self-esteem. AB - The aim of this study was to explore the relationships among perceived organizational support, career success, self-esteem and intention to remain. A cross-sectional study was designed, and subjects were recruited from six nonprofit organizations in China in spring 2015. A convenience sample of 610 nurses answered a survey with questions related to their ideas about their work. Structural equation modelling analyses were conducted. The results revealed that perceived organizational support was positively associated with intention to remain and career success, which, in turn, mediated the relationship between perceived organizational support and intention to remain. We also found that self esteem mediated the relationships between perceived organizational support and career success and between career success and intention to remain. Higher perceived organizational support, career success and self-esteem can increase intention to remain in Chinese nurses. PMID- 26669588 TI - Hypoglycaemia, a global cause for concern. PMID- 26669587 TI - Oxysterol mixture and, in particular, 27-hydroxycholesterol drive M2 polarization of human macrophages. AB - Macrophages play a crucial role in atherosclerosis progression. Classically activated M1 macrophages have been found in rupture-prone atherosclerotic plaques whereas alternatively activated macrophages, M2, localize in stable plaque. Macrophage accumulation of cholesterol and of its oxidized derivatives (oxysterols) leads to the formation of foam cells, a hallmark of atherosclerotic lesions. In this study, the effects of oxysterols in determining the functional polarization of human macrophages were investigated. Monocytes, purified from peripheral blood mononuclear cells of healthy donors, were differentiated into macrophages (M0) and treated with an oxysterol mixture, cholesterol, or ethanol, every 4 H for a total of 4, 8, and 12 H. The administration of the compounds was repeated in order to maintain the levels of oxysterols constant throughout the treatment. Compared with ethanol treatment, the oxysterol mixture decreased the surface expression of CD36 and CD204 scavenger receptors and reduced the amount of reactive oxygen species whereas it did not affect either cell viability or matrix metalloprotease-9 activity. Moreover, the oxysterol mixture increased the expression of both liver X receptor alpha and ATP-binding cassette transporter 1. An enhanced secretion of the immunoregulatory cytokine IL-10 accompanied these events. The results supported the hypothesis that the constant levels of oxysterols and, in particular, of 27-hydroxycholesterol stimulate macrophage polarization toward the M2 immunomodulatory functional phenotype, contributing to the stabilization of atherosclerotic plaques. PMID- 26669589 TI - Serum miR-21, miR-26a and miR-101 as potential biomarkers of hepatocellular carcinoma. AB - AIM: This study aimed to investigate the expressions of serum miR-21, miR-26a and miR-101 in hepatocellular carcinoma (HCC) and their diagnostic value. METHODS: Serum levels of miR-21, miR-26a and miR-101 were detected by quantitative real time polymerase chain reaction (qRT-PCR) in 52 HCC patients, 42 chronic hepatitis (CH) patients and 43 healthy controls. ROC curve analysis was performed to evaluate the diagnostic value. Clinical parameters were collected. RESULTS: Serum level of miR-21 was higher while miR-26a and miR-101 were significantly lower in HCC patients than those in healthy controls (P<0.05, P<0.001 and P<0.05, respectively). Serum levels of miR-26a and miR-101 were significantly lower in HCC patients than those in CH patients (P<0.001 and P<0.05). ROC curve analyses revealed that miR-21, miR-26a and miR-101 could differentiate HCC patients from healthy controls, the area under ROC curve (AUC) were 0.621 (67.4% sensitivity and 55.8% specificity), 0.754 (51.9% sensitivity and 95.2% specificity) and 0.631 (47.1% sensitivity and 81% specificity), respectively. Combination of miRNAs and alpha-fetoprotein (AFP) yielded an AUC of 0.914 with 87.0% sensitivity and 78.0% specificity. miR-26a and miR-101 had diagnostic potential for differentiating HCC from CH with AUC of 0.762 (75% sensitivity and 70% specificity) and 0.623 (54.9% sensitivity and 76.9% specificity). Combination of miR-26a, miR-101 and AFP yielded an improved AUC than AFP alone (0.854 vs. 0.683). Notably, miR-26a could differentiate small tumors HCC (<=3cm) from CH with an AUC of 0.753 (80% sensitivity and 62.5% specificity). CONCLUSIONS: Serum miR-21, miR-26a and miR 101 are deregulated in HCC and can serve as potential biomarkers. Combination of these miRNAs and AFP provide a better detection than AFP alone. Serum miR-26a is a promising biomarker for early detection of HCC. PMID- 26669590 TI - Helicobacter pylori with high thioredoxin-1 expression promotes stomach carcinogenesis in Mongolian gerbils. AB - OBJECTIVE: Previous studies by this group have shown that Helicobacter pylori with high thioredoxin-1 (Trx1) expression might be involved in stomach carcinogenesis in vitro. To study histopathological changes of the stomach mucosa in vivo, a Mongolian gerbil model infected with H. pylori with high Trx1 expression was established. METHODS: Healthy, male Mongolian gerbils (n=75) were randomly divided into 3 groups: controls (n=15), which were not infected with H. pylori, high Trx1 (n=30) which were infected with H. pylori with high Trx1 expression and low Trx1 (n=30) which were infected with low Trx1 expression H. pylori. The animals were sacrificed at 4, 20, 34, 48, 70 and 90 weeks after inoculation. RESULTS: The Mongolian gerbil model of H. pylori infection was successfully established. Three animals died during the study, leaving 72 animals (controls, n=14; low Trx1, n=29; high Trx1, n=29) examined on schedule. Histopathological analysis of the stomach mucosa showed gradually increased aggravation over time in the high and low Trx1 groups. Compared with control and low Trx1, the histopathological changes were more serious in the high Trx1 group. At 90 weeks, no abnormal changes were found in the controls, but 62.5% of the high Trx1 group and 33.3% of the low Trx1 showed adenocarcinomas. The H. pylori Trx1 level in gastric cancer tissue was significantly higher than that from gastritis tissue. Within gastric cancer cells, high Trx1 expression in H. pylori significantly upregulated cyclin D1. CONCLUSIONS: High Trx1 expression in H. pylori promoted stomach carcinogenesis. More studies are needed to confirm this finding. PMID- 26669591 TI - Live Cell Discovery of Microbial Vitamin Transport and Enzyme-Cofactor Interactions. AB - The rapid completion of microbial genomes is inducing a conundrum in functional gene discovery. Novel methods are needed to shorten the gap between characterizing a microbial genome and experimentally validating bioinformatically predicted functions. Of particular importance are transport mechanisms, which shuttle nutrients such as B vitamins and metabolites across cell membranes and are required for the survival of microbes ranging from members of environmental microbial communities to pathogens. Methods to accurately assign function and specificity for a wide range of experimentally unidentified and/or predicted membrane-embedded transport proteins, along with characterization of intracellular enzyme-cofactor associations, are needed to enable a significantly improved understanding of microbial biochemistry and physiology, microbial interactions, and microbial responses to perturbations. Chemical probes derived from B vitamins B1, B2, and B7 have allowed us to experimentally address the aforementioned needs by identifying B vitamin transporters and intracellular enzyme-cofactor associations through live cell labeling of the filamentous anoxygenic photoheterotroph, Chloroflexus aurantiacus J-10-fl, known to employ mechanisms for both B vitamin biosynthesis and environmental salvage. Our probes provide a unique opportunity to directly link cellular activity and protein function back to ecosystem and/or host dynamics by identifying B vitamin transport and cofactor-dependent interactions required for survival. PMID- 26669592 TI - Low-Dose Volume-Perfusion CT of the Brain: Effects of Radiation Dose Reduction on Performance of Perfusion CT Algorithms. AB - PURPOSE: We aimed to compare different computed tomography (CT) perfusion post processing algorithms regarding image quality of perfusion maps from low-dose volume perfusion CT (VPCT) and their diagnostic performance regarding the detection of ischemic brain lesions. METHODS AND MATERIALS: We included VPCT data of 21 patients with acute stroke (onset < 6h), which were acquired at 80 kV and 180 mAs. Low-dose VPCT datasets with 72 mAs (40 % of original dose) were generated using realistic low-dose simulation. Perfusion maps (cerebral blood volume (CBV); cerebral blood flow (CBF) from original and low-dose datasets were generated using two different commercially available post-processing methods: deconvolution-based method (DC) and maximum slope algorithm (MS). The resulting DC and MS perfusion maps were compared regarding perfusion values, signal-to noise ratio (SNR) as well as image quality and diagnostic accuracy as rated by two blinded neuroradiologists. RESULTS: Quantitative perfusion parameters highly correlated for both algorithms and both dose levels (r >= 0.613, p < 0.001). Regarding SNR levels and image quality of the CBV maps, no significant differences between DC and MS were found (p >= 0.683). Low-dose MS CBF maps yielded significantly higher SNR levels (p < 0.001) and quality scores (p = 0.014) than those of DC. Low-dose CBF and CBV maps from both DC and MS yielded high sensitivity and specificity for the detection of ischemic lesions (sensitivity >= 0.82, specificity >= 0.90). CONCLUSION: Our results indicate that both methods produce diagnostically sufficient perfusion maps from simulated low dose VPCT. However, MS produced CBF maps with significantly higher image quality and SNR than DC, indicating that MS might be more suitable for low-dose VPCT imaging. PMID- 26669593 TI - Trigeminocardiac Reflex During the Endovascular Treatment of Intracranial Vascular Disease: A Report of Two Cases. PMID- 26669594 TI - Nutrient requirements and low-cost balanced diets, based on seasonally available local feedstuffs, for local pigs on smallholder farms in Western Kenya. AB - Growth performance of pigs on smallholder farms in the tropics is low. Lack of feedstuffs, seasonal feed shortages, and feeding nutritionally unbalanced diets contribute to slow growth. Low-cost balanced diets are needed to improve pig performance. In this study, we estimated the nutrient requirements of local pigs on smallholder farms in Kenya and developed balanced low-cost diets using seasonally available local feedstuffs. Diets were formulated to provide pigs with 80 % of the nutrient density in corn and soybean meal-based (reference) diets to minimize the cost per unit of energy and other nutrients. Estimated requirements for starting and growing pigs (8 to 35 kg body weight) were as follows: digestible energy (DE) 2960 kcal/kg of dry matter (DM), standardized ileal digestibility (SID) lysine 5.8 g/kg of DM, calcium 2.8 g/kg of DM, standardized total tract digestible (STTD) phosphorous 1.4 g/kg of DM, and crude protein 85 g/kg of DM. Nutrient requirements of local pigs on smallholder farms in Kenya were lower than those of exotic breed pigs raised in commercial settings. Seasonally available local feedstuffs were used to develop low-cost balanced diets. Twenty-two diets are presented based on season, cost, and feedstuff availability. This study has broad applicability as a case study of an approach that could be applied in other tropical regions in which smallholder pig keeping is practiced and where local feedstuffs for pigs are available seasonally. PMID- 26669595 TI - Faecal cortisol concentrations as indicator of stress during intensive fattening of beef cattle in a humid tropical environment. AB - The study evaluated the concentrations of faecal cortisol metabolites (FCM) in intensively fattened beef cattle from a feedlot in a humid tropical environment. A total of 360 bulls weighing 271-371 kg were kept confined in pens from the start to the end of the fattening period (FP). At 24 h after arriving at the feedlot, cattle were distributed into the pens according to their live weight: 271-320 kg, 321-370 kg, and >370 kg. At the start of the FP, four pens of each weight group were randomly selected, and in each of them 10 faecal samples were obtained from 10 randomly selected bulls; this sampling was repeated in the same pens and in each weight group at the middle and end of the FP. The FCM were measured through enzyme immunoassay. The 271-320 kg group had higher FCM at the end of the FP (P < 0.05), the 321-370 kg group had similar FCM throughout the FP (P > 0.05), and the >370 kg group showed higher FCM at the start and end of the FP (P < 0.05). Higher FCM were observed at the middle of the FP in the 321-370 kg group, and at the end of the FP in the 271-320 kg and >370 kg groups (P < 0.05). Mean FCM obtained throughout the FP were within normal ranges for cattle, suggesting that appropriate management in feedlots in humid-tropical regions can provide bulls with a low-stress environment. PMID- 26669596 TI - High seroprevalence of Coxiella burnetii in dairy cattle in China. AB - Coxiella burnetii is the agent of Q fever, a zoonosis which occurs worldwide. As there is little reliable data on the organism in China, we investigated C. burnetii infections in dairy cattle herds around the country. Opportunistic whole blood samples were collected from 1140 dairy cattle in 19 herds, and antibodies to phase I and II C. burnetii antigens were detected using commercial ELISA kits. Seropositive cattle (381/1140, 33 %) were detected in 13 of the 15 surveyed provinces and in 16 of the 19 herds (84 %) studied. Our data indicates C. burnetii is widespread in China and that animal and human health workers should be aware of the possibility of Q fever infection in their patients. PMID- 26669597 TI - Identification of putative phosphoproteins in wheat spikes induced by Fusarium graminearum. AB - MAIN CONCLUSION: Phosphorylation and dephosphorylation events were initiated in wheat scab resistance. The putative FHB-responsive phosphoproteins are mainly involved in three functional groups and contain at least one tyrosine, serine, or threonine phosphorylation site. Fusarium head blight (FHB), caused by Fusarium graminearum, is a severe disease in wheat. Protein phosphorylation plays an important role in plant-pathogen interactions, however, a global analysis of protein phosphorylation in response to FHB infection remains to be explored. To study the effect of FHB on the phosphorylation state of wheat proteins, proteins extracted from spikes of a resistant wheat cultivar after 6 h of inoculation with F. graminearum or sterile H2O were separated by two-dimensional gel electrophoresis, and then the immunodetection of putative phosphoproteins was conducted by Western blotting using specific anti-phosphotyrosine antibody, anti phosphothreonine antibody and anti-phosphoserine antibody. A total of 35 phosphorylated signals was detected and protein identities of 28 spots were determined. Functional categorization showed that the putative FHB-responsive phosphoproteins were mainly involved in defense/stress response, signal transduction, and metabolism. The phosphorylation status of proteins associated with signaling pathways mediated by salicylic acid, calcium ions, small GTPase, as well as with detoxification, reactive oxygen species scavenging, antimicrobial compound synthesis, and cell wall fortification was regulated in wheat spikes in response to F. graminearum infection. The present study reveals dynamics of wheat phosphoproteome in response to F. graminearum infection and suggests an important role of protein Ser/Thr/Tyr phosphorylation in fundamental mechanisms of wheat scab resistance. PMID- 26669598 TI - Eukaryotic Hsp70 chaperones in the intermembrane space of chloroplasts. AB - MAIN CONCLUSION: Multiple eukaryotic Hsp70 typically localized in the cytoplasm are also distributed to the intermembrane space of chloroplasts and might thereby represent the missing link in energizing protein translocation. Protein translocation into organelles is a central cellular process that is tightly regulated. It depends on signals within the preprotein and on molecular machines catalyzing the process. Molecular chaperones participate in transport and translocation of preproteins into organelles to control folding and to provide energy for the individual steps. While most of the processes are explored and the components are identified, the transfer of preproteins into and across the intermembrane space of chloroplasts is not yet understood. The existence of an energy source in this compartment is discussed, because the required transit peptide length for successful translocation into chloroplasts is shorter than that found for mitochondria where energy is provided exclusively by matrix chaperones. Furthermore, a cytosolic-type Hsp70 homologue was proposed as component of the chloroplast translocon in the intermembrane space energizing the initial translocation. The molecular identity of such intermembrane space localized Hsp70 remained unknown, which led to a controversy concerning its existence. We identified multiple cytosolic Hsp70s by mass spectrometry on isolated, thermolysin-treated Medicago sativa chloroplasts. The localization of these Hsp70s of M. sativa or Arabidopsis thaliana in the intermembrane space was confirmed by a self-assembly GFP-based in vivo system. The localization of cytosolic Hsp70s in the stroma of chloroplasts or different mitochondrial compartments could not be observed. Similarly, we could not identify any cytosolic Hsp90 in the intermembrane space of chloroplast. With respect to our results we discuss the possible targeting and function of the Hsp70 found in the intermembrane space. PMID- 26669599 TI - New Perspectives in Pediatric Neurology-Multiple Sclerosis. AB - With the creation of consensus definitions for pediatric multiple sclerosis (MS) and other acquired demyelinating syndromes, there has been an increased recognition, improved collaboration, and expanded access to care for children with central nervous system demyelination. As a result, clinicians and researchers have been able to learn more about clinical features specific to pediatric MS, the associated genetic and environmental risk factors, and its prognosis and comorbidities. Treatment options have also expanded significantly in the past few years and insight has been gained into the challenges with adherence and tolerability of these medications in the pediatric population. Emerging therapies are now being studied in the context of pediatric clinical trials and may prove to be safe and effective options for patients with aggressive disease. PMID- 26669600 TI - Formal models in animal-metacognition research: the problem of interpreting animals' behavior. AB - Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly. PMID- 26669601 TI - Using clinical decision support as a means of implementing a universal postpartum depression screening program. AB - A major barrier to the diagnosis of postpartum depression (PPD) includes symptom detection. The lack of awareness and understanding of PPD among new mothers, the variability in clinical presentation, and the various diagnostic strategies can increase this further. The purpose of this study was to test the feasibility of adding clinical decision support (CDS) to the electronic health record (EHR) as a means of implementing a universal standardized PPD screening program within a large, at high risk, population. All women returning to the Mount Sinai Hospital OB/GYN Ambulatory Practice for postpartum care between 2010 and 2013 were presented with the Edinburgh Postnatal Depression Scale (EPDS) in response to a CDS "hard stop" built into the EHR. Of the 2102 women who presented for postpartum care, 2092 women (99.5 %) were screened for PPD in response to a CDS hard stop module. Screens were missing on ten records (0.5 %) secondary to refusal, language barrier, or lack of clarity in the EHR. Technology is becoming increasingly important in addressing the challenges faced by health care providers. While the identification of PPD has become the recent focus of public health concerns secondary to the significant social burden, numerous barriers to screening still exist within the clinical setting. The utility of adding CDS in the form of a hard stop, requiring clinicians to enter a standardized PPD mood assessment score to the patient EHR, offers a sufficient way to address a primary barrier to PPD symptom identification at the practitioner level. PMID- 26669602 TI - Being Kind to Your Future Self: Probability Discounting of Health Decision Making. AB - INTRODUCTION: Nearly 50 % of patients with chronic medical illness exhibit poor treatment adherence. When making treatment decisions, these patients must balance the probability of current side effects against the probability of long-term benefits. This study examines if the behavioral economic construct of probability discounting can be used to explain treatment decisions in chronic disease. METHODS: Thirty-eight nonadherent and 39 adherent patients with multiple sclerosis (MS) completed a series of hypothetical treatment scenarios with varied risk and benefit probabilities. RESULTS: As described by a hyperbolic probability discounting model, all patients reported decreased medication initiation as the probability of treatment efficacy decreased and the probability of treatment side effects increased. When compared to adherent patients, nonadherent patients significantly devalued treatment efficacy and inflated treatment risk. DISCUSSION: The methods in this study can be used to identify optimal risk/benefit ratios for treatment development and inform the process by which patients make treatment decisions. PMID- 26669603 TI - The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma. AB - Uncontrolled proliferation and cell growth is the hallmark of many different malignant diseases, including sarcomas. Cyclin-dependent kinases (CDKs) are members of the serine/threonine protein kinase family and play crucial roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. In addition, several CDKs influence multiple targets and phosphorylate transcription factors involved in tumorigenesis. There are many examples linking dysregulated activation and expression of CDKs to tumors, and targeting CDKs in tumor cells has become a promising therapeutic strategy. More recently, the Food and Drug Administration (FDA) has approved the CDK4/6 inhibitor palbociclib for treating metastatic breast cancer. In sarcomas, high levels of CDK mRNA and protein expression have been found in most human sarcoma cells and patient tissues. Many studies have demonstrated consistent results in which inhibition of different CDKs decrease sarcoma cell growth and induce apoptosis. Therefore, CDKs comprise an attractive set of targets for novel anti sarcoma drug development. In this review, we discuss the roles of different members of CDKs in various sarcomas and provide a pre-clinical overview of promising therapeutic potentials of targeting CDKs with a special emphasis on sarcoma. PMID- 26669604 TI - Findings from Structural MR Imaging in Military Traumatic Brain Injury. AB - PURPOSE: To describe the initial neuroradiology findings in a cohort of military service members with primarily chronic mild traumatic brain injury (TBI) from blast by using an integrated magnetic resonance (MR) imaging protocol. MATERIALS AND METHODS: This study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI (not explicitly age- and sex matched). MR examinations were performed at 3 T primarily with three-dimensional volume imaging at smaller than 1 mm(3) voxels for the structural portion of the examination. The structural portion of this examination, including T1-weighted, T2-weighted, before and after contrast agent administrtion T2 fluid attenuation inversion recovery, and susceptibility-weighted images, was evaluated by neuroradiologists by using a modified version of the neuroradiology TBI common data elements (CDEs). Incident odds ratios (ORs) between the TBI participants and a comparison group without TBI were calculated. RESULTS: The 834 participants were diagnosed with predominantly chronic (mean, 1381 days; median, 888 days after injury) and mild (92% [768 of 834]) TBI. Of these participants, 84.2% (688 of 817) reported one or more blast-related incident and 63.0% (515 of 817) reported loss of consciousness at the time of injury. The presence of white matter T2-weighted hyperintense areas was the most common pathologic finding, observed in 51.8% (432 of 834; OR, 1.75) of TBI participants. Cerebral microhemorrhages were observed in a small percentage of participants (7.2% [60 of 834]; OR, 6.64) and showed increased incidence with TBI severity (P < .001, moderate and severe vs mild). T2-weighted hyperintense areas and microhemorrhages did not collocate by visual inspection. Pituitary abnormalities were identified in a large proportion (29.0% [242 of 834]; OR, 16.8) of TBI participants. CONCLUSION: Blast-related injury and loss of consciousness is common in military TBI. Structural MR imaging demonstrates a high incidence of white matter T2 weighted hyperintense areas and pituitary abnormalities, with a low incidence of microhemorrhage in the chronic phase. PMID- 26669605 TI - "Making Do" Decisions: How Home Healthcare Personnel Manage Their Exposure to Home Hazards. AB - This study describes the decision-making processes home healthcare personnel (HHP) use to manage their personal health and safety when managing hazards in client homes. A professionally diverse national sample of 68 HHP participated in individual semi-structured interviews and focus group discussions, and described their decision making and strategies for hazard management in their work environments. HHP described 353 hazard management dilemmas within 394 specifically identified hazards, which were clustered within three broader categories: electrical/fire, slip/trip/lift, and environmental exposures. HHP described multiple types of "making do" decisions for hazard management solutions in which perceived and actual resource limitations constrained response options. A majority of hazard management decisions in the broader hazards categories (72.5%, 68.5%, and 63.5%, respectively) were classifiable as less than optimal. These findings stress the need for more support of HHPs, including comprehensive training, to improve HHP decision making and hazard management strategies, especially in context of resource constraints. PMID- 26669607 TI - Psoas haematoma mimicking lumbar radiculopathy. PMID- 26669606 TI - Constitutive modeling of ascending thoracic aortic aneurysms using microstructural parameters. AB - Ascending thoracic aortic aneurysm (ATAA) has been associated with diminished biomechanical strength and disruption in the collagen fiber microarchitecture. Additionally, the congenital bicuspid aortic valve (BAV) leads to a distinct extracellular matrix structure that may be related to ATAA development at an earlier age than degenerative aneurysms arising in patients with the morphological normal tricuspid aortic valve (TAV). The purpose of this study was to model the fiber-reinforced mechanical response of ATAA specimens from patients with either BAV or TAV. This was achieved by combining image-analysis derived parameters of collagen fiber dispersion and alignment with tensile testing data. Then, numerical simulations were performed to assess the role of anisotropic constitutive formulation on the wall stress distribution of aneurysmal aorta. Results indicate that both BAV ATAA and TAV ATAA have altered collagen fiber architecture in the medial plane of experimentally-dissected aortic tissues when compared to normal ascending aortic specimens. The study findings highlight that differences in the collagen fiber distribution mostly influences the resulting wall stress distribution rather than the peak stress. We conclude that fiber reinforced constitutive modeling that takes into account the collagen fiber defect inherent to the aneurysmal ascending aorta is paramount for accurate finite element predictions and ultimately for biomechanical-based indicators to reliably distinguish the more from the less 'malignant' ATAAs. PMID- 26669608 TI - Transcultural care and individuals with an intellectual disability. AB - Healthcare delivery today reflects a history of change, which has responded to lifestyle changes, cultural diversity, population needs and expectations. In today's health-care environment it is crucial for health-care professionals to be mindful of cultural factors that affect health. These factors include the intricate interdependent biological, intellectual, psychological, social and spiritual needs of the individuals they work with. However, challenges exists for those who provide healthcare to people with intellectual disability. This article presents the transcultural care challenges for people with intellectual disability, through highlighting the biomedical/sociocultural perspectives of healthcare, communication and inequality experienced by those with intellectual disability. As a population group, people with intellectual disability can often be considered part of a larger culture rather than a culture within itself, and this article endeavours to emphasize that intellectual disability is in itself a coterminous culture. By highlighting intellectual disability as a cultural community within a larger community, requiring a transcultural response to care on several levels health-care professionals can provide culturally compatible care to those with intellectual disability within a transcultural framework to augment a person-centred approach to care. PMID- 26669609 TI - Effects of RNA interference therapy against herpes simplex virus type 1 encephalitis. AB - BACKGROUND: Herpetic encephalitis (HSE) is caused mainly by herpes simplex virus type 1 (HSV-1) with an annual incidence of 1-4 cases/million inhabitants. Currently, HSE treatment faces difficulties such as the use of antivirals with elevated toxicity, metabolic side effects and HSV-1 resistance. An alternative to antivirals is the use of small interfering RNA (siRNA) as a viral replication inhibitor. In this work, siRNA targeting the UL-39 region was evaluated for HSE treatment in vivo. METHODS: BALB/c mice were inoculated with HSV-1 and treated with siRNA. The treatment was evaluated through kinetics of HSV-1 replication inhibition, number of siRNA doses administered and treatment with siRNA plus acyclovir. All groups were evaluated for signs of HSE, mortality and HSV-1 replication inhibition. RESULTS: The treated group of the kinetic experiment demonstrated a reduction of HSE signs and an HSV-1 replication inhibition of 43.6 99.9% in the brain and 53-98% in trigeminal ganglia (TG). Animals treated with one or two doses of siRNA had a prolonged survival time, reduced clinical signs of HSE and HSV-1 replication inhibition of 67.7% in brains and 85.7% in TG of animals treated with two doses of siRNA. Also, animals treated with siRNA plus acyclovir demonstrated reduced signs of HSE and mortality, as well as HSV-1 replication inhibition in the brain (83.2%) and TG (74.5%). CONCLUSIONS: These findings demonstrated that siRNA was capable of reducing HSE clinical signs, prolonging survival time and inhibiting HSV-1 replication in mice. Thus, siRNA can be a potential alternative to the standard HSE treatment especially to reduce clinical signs and extend survival time in vivo. PMID- 26669610 TI - Zebrafish as a Model for Systems Medicine R&D: Rethinking the Metabolic Effects of Carrier Solvents and Culture Buffers Determined by (1)H NMR Metabolomics. AB - Zebrafish is a frequently employed model organism in systems medicine and biomarker discovery. A crosscutting fundamental question, and one that has been overlooked in the field, is the "system-wide" (omics) effects induced in zebrafish by metabolic solvents and culture buffers. Indeed, any bioactivity or toxicity test requires that the target compounds are dissolved in an appropriate nonpolar solvent or aqueous media. It is important to know whether the solvent or the buffer itself has an effect on the zebrafish model organism. We evaluated the effects of two organic carrier solvents used in research with zebrafish, as well as in drug screening: dimethyl sulfoxide (DMSO) and ethanol, and two commonly used aqueous buffers (egg water and Hank's balanced salt solution). The effects of three concentrations (0.01, 0.1, and 1%) of DMSO and ethanol were tested in the 5-day-old zebrafish embryo using proton nuclear magnetic resonance ((1)H NMR) based metabolomics. DMSO (1% and 0.1%, but not 0.01%) exposure significantly decreased the levels of adenosine triphosphate (ATP), betaine, alanine, histidine, lactate, acetate, and creatine (p < 0.05). By contrast, ethanol exposure did not alter the embryos' metabolome at any concentration tested. The two different aqueous media noted above impacted the zebrafish embryo metabolome as evidenced by changes in valine, alanine, lactate, acetate, betaine, glycine, glutamate, adenosine triphosphate, and histidine. These results show that DMSO has greater effects on the embryo metabolome than ethanol, and thus is used with caution as a carrier solvent in zebrafish biomarker research and oral medicine. Moreover, the DMSO concentration should not be higher than 0.01%. Careful attention is also warranted for the use of the buffers egg water and Hank's balanced salt solution in zebrafish. In conclusion, as zebrafish is widely used as a model organism in life sciences, metabolome changes induced by solvents and culture buffers warrant further attention for robust systems science, and precision biomarkers that will stand the test of time. PMID- 26669611 TI - Effect of feeding graded levels of crude protein on nutrient utilization and feather growth in Lady Amherst's pheasants. AB - In order to find out the optimum level of crude protein (CP) in the diet of captive Lady Amherst's pheasants (LAP) on molt, 18 male birds were randomly distributed into three groups of six each in an experiment based on completely randomized block design. The CP content of the diets of birds in groups I, II, and III was 13.4, 16.5, and 19.1%, respectively. Intake and apparent balance of nitrogen increased linearly (P < 0.001) as CP content of the diet increased. Intake and utilization of energy, calcium, and phosphorous were similar among groups. Body mass change and growth rate of feathers were significantly (P < 0.01) lower in group I as compared to groups II and III. There was a positive co relationship between ME intake and change in body weight (R(2) = 0.89, F = 126.4, P < 0.001). Regression analysis indicates that LAP can maintain body mass when ME supply is 122.2 Kcal/kg BW(0.75)/d. Linear relationships between intake and apparent retention of N, Ca, and P as expressed on mg/kg BW(0.75)/d were all significant. Apparent nitrogen retention, and mean feather growth rate was lower in birds fed diet containing 13.4% CP. Feeding of the diets containing 16.5% CP resulted in improved retention of nitrogen, and mean feather growth rate. Further increase in dietary concentration of CP to 19.1% showed no further improvement. It was concluded that a diet containing 16.5% CP would be optimum for Lady Amherst's pheasants during molt. PMID- 26669612 TI - Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method. AB - In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350mL/min yielding retention times of 1.7min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0MUg/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 92.2 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab. PMID- 26669613 TI - Trace enrichment and characterization of polyphenols in Bistort Rhizoma using weak anion-exchange solid phase extraction and high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. AB - The analysis of trace constituents in herbal medicines has always been a challenge due to complex matrices and structural diversities. In this work, a pH sensitive solid phase extraction (SPE) procedure capable of enriching trace polyphenols in Bistort Rhizoma (BR) was proposed and preliminary chemical characterization was accomplished by high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS). A weak anion-exchange SPE column packed with divinylbenzene/vinylpyrrolidone bonding quaternary amine group was employed for anionic extraction, and the target fraction was obtained by eluting with acidic methanol (apparent pH 1.9). On the other hand, the MS/MS fragmentation rules of four reference polyphenols in negative ion mode were outlined. Using these rules, a total of 31 polyphenols including 20 benzoyl derivatives and 11 caffeoyl derivatives were screened out from BR extract, of which 26 trace members were found for the first time in this herb. Those findings demonstrated that the anion-exchange SPE could enhance the detection capability and selectivity for plant polyphenols in the LC-MS analysis and the strategy for deducing structures could be applied for analysis of polyphenols in BR and other herbal medicines. PMID- 26669614 TI - An experimental validated in silico model to assess Staphylococcus aureus growth kinetics on different pork products. AB - AIMS: To gain an understanding of the growth kinetics of Staphylococcus aureus to ensure the safety of pork, and to develop a predictive growth model of Staph. aureus in raw pork, ham and sausage pork under specific storage time and temperature conditions. METHODS AND RESULTS: Growth of Staph. aureus was evaluated at 5-40 degrees C using 5-6 replicates in each sampling time in order to capture experimental variability. Growth curves were fit to Baranyi model to estimate Lag time (lambda) and maximum growth rate (MUmax). The effect of temperature on lambda and MUmax was modelled using natural logarithm of lambda and square root of MUmax. The variability between repetitions was higher at 15, 20 and 40 degrees C than observed at 25, 30 and 35 degrees C. After only 3 and 2 days of storage at 5 and 10 degrees C, respectively, Staph. aureus populations decreased to limit of detection (<=1 log CFU g(-1) ). Staphylococcus aureus populations on ham presented higher MUmax in comparison to those grown on raw pork and sausage. Linear regression lines showed that Staph. aureus populations in ham grew faster than those observed in sausage and raw pork. Staph. aureus presented a theoretical minimum growth temperature (Tmin ) depending on the processed pork products, which were different from in raw pork. CONCLUSION: Staphylococcus aureus model predicts faster growth in ham compared to raw pork and sausage. The validation of models showed good predictions, suggesting that the developed models are useful in estimating growth kinetics of Staph. aureus in different pork products. SIGNIFICANCE AND IMPACT OF THIS STUDY: Established here is a data-driven, in silico model on Staph. aureus growth kinetics on different pork products. The model is extensively validated by experiments and simulations and further supported by comparisons to previous modelling efforts in other species. PMID- 26669615 TI - Protein adsorption, platelet adhesion, and bacterial adhesion to polyethylene glycol-textured polyurethane biomaterial surfaces. AB - Traditional strategies for surface modification to enhance the biocompatibility of biomaterials often focus on a single route utilizing either chemical or physical approaches. This study combines the chemical and physical treatments as applied to poly(urethane urea) (PUU) biomaterials to enhance biocompatibility at the interface for inhibiting platelet-related thrombosis or bacterial adhesion induced microbial infections. PUU films were first textured with submicron patterns by a soft lithography two-stage replication process, and then were grafted with polyethylene glycol (PEG). A series of biological response experiments including protein adsorption, platelet adhesion/activation, and bacterial adhesion/biofilm formation showed that PEG-grafted submicron textured biomaterial surfaces were resistant to protein adsorption, and greatly increased the efficiency in reducing both platelet adhesion/activation and bacterial adhesion/biofilm formation due to the additive effects of physical topography and grafted PEG. Results suggest that a combination of chemical modification and surface texturing will be more efficient in preventing biomaterial-associated thrombosis and infection of biomaterials. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 668-678, 2017. PMID- 26669616 TI - The presence of the anti-inflammatory protein MAM, from Faecalibacterium prausnitzii, in the intestinal ecosystem. PMID- 26669618 TI - High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis. AB - Compared with routine microscopy imaging of a few analytes at a time, rapid scanning through the whole sample area of a microscope slide to locate every single target object offers many advantages in terms of simplicity, speed, throughput, and potential for robust quantitative analysis. Existing techniques that accommodate solid-phase samples incorporating individual micrometer-sized targets generally rely on digital microscopy and image analysis, with intrinsically low throughput and reliability. Here, we report an advanced on-the fly stage scanning method to achieve high-precision target location across the whole slide. By integrating X- and Y-axis linear encoders to a motorized stage as the virtual "grids" that provide real-time positional references, we demonstrate an orthogonal scanning automated microscopy (OSAM) technique which can search a coverslip area of 50 * 24 mm(2) in just 5.3 min and locate individual 15 MUm lanthanide luminescent microspheres with standard deviations of 1.38 and 1.75 MUm in X and Y directions. Alongside implementation of an autofocus unit that compensates the tilt of a slide in the Z-axis in real time, we increase the luminescence detection efficiency by 35% with an improved coefficient of variation. We demonstrate the capability of advanced OSAM for robust quantification of luminescence intensities and lifetimes for a variety of micrometer-scale luminescent targets, specifically single down-shifting and upconversion microspheres, crystalline microplates, and color-barcoded microrods, as well as quantitative suspension array assays of biotinylated-DNA functionalized upconversion nanoparticles. PMID- 26669619 TI - Nucleophosmin mutation in de-novo acute myeloid leukemia. AB - OBJECTIVE: Acute myeloid leukemia (AML) with mutated nucleophosmin gene (NPM1) has distinctive clinical, hematological and molecular features, and is included as a provisional entity in 2008 World Health Organization classification. In this study, we analyzed the frequency and features of AML with mutated NPM1 in Indian patients. METHODS: One-hundred consecutive patients of de-novo AML were evaluated for NPM1 mutation and their features were compared with unmutated NPM1 patients. RESULTS: AML with mutated NPM1 was seen in 21% cases. There was female preponderance with median age of 51 years. Distinguishing Features in mutated group were less bleeding manifestations and bone pains; more lymphadenopathy; higher median total leukocyte and platelet count; less frequency of pancytopenia and more preserved megakaryocytes. Morphologically, cup-shaped nuclei in peripheral blood blasts correlated with NPM1 mutation (p <0.01), but not bone marrow blasts. Among the French-American-British subtypes, NPM1 mutation was seen in M1, M4 and M2 subtypes but not in M0 and M3. Immunophenotypically, there was statistically significant negativity for CD34, strong association with monocytic markers (especially CD11c), CD123 was seen at higher frequency and higher mean fluorescence intensity (MFI) values for CD33 were observed in mutated cases. CONCLUSIONS: Important findings in this study that have not been highlighted in detail in previous studies in NPM1-mutated cases include less bleeding manifestations and bone pains, lower frequency of pancytopenia and more preserved magakaryocytes, higher CD123 expression and higher MFI values for CD33. Presence of blasts with cup-shaped nuclei correlated with NPM1 mutation. PMID- 26669617 TI - Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. AB - OBJECTIVE: The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we investigate the impact of TIBs and their interaction with T cells on HCC patient prognosis. DESIGN: Tissue samples were obtained from 112 patients with HCC from Singapore, Hong Kong and Zurich and analysed using immunohistochemistry and immunofluorescence. RNA expression of CD19, CD8A, IFNG was analysed using quantitative PCR. The phenotype of freshly isolated TILs was analysed using flow cytometry. A mouse model depleted of mature B cells was used for functional study. RESULTS: Tumour-infiltrating T cells and B cells were observed in close contact with each other and their densities are correlated with superior survival in patients with HCC. Furthermore, the density of TIBs was correlated with an enhanced expression of granzyme B and IFN-gamma, as well as with reduced tumour viability defined by low expression of Ki-67, and an enhanced expression of activated caspase-3 on tumour cells. CD27 and CD40 costimulatory molecules and TILs expressing activation marker CD38 in the tumour were also correlated with patient survival. Mice depleted of mature B cells and transplanted with murine hepatoma cells showed reduced tumour control and decreased local T cell activation, further indicating the important role of B cells. CONCLUSIONS: The close proximity of tumour-infiltrating T cells and B cells indicates a functional interaction between them that is linked to an enhanced local immune activation and contributes to better prognosis for patients with HCC. PMID- 26669620 TI - Early use of orthographic information in spoken word recognition: Event-related potential evidence from the Korean language. AB - This study examines whether orthographic information is used during prelexical processes in spoken word recognition by investigating ERPs during spoken word processing for Korean words. Differential effects due to orthographic syllable neighborhood size and sound-to-spelling consistency on P200 and N320 were evaluated by recording ERPs from 42 participants during a lexical decision task. The results indicate that P200 was smaller for words whose orthographic syllable neighbors are large in number rather than those that are small. In addition, a word with a large orthographic syllable neighborhood elicited a smaller N320 effect than a word with a small orthographic syllable neighborhood only when the word had inconsistent sound-to-spelling mapping. The results provide support for the assumption that orthographic information is used early during the prelexical spoken word recognition process. PMID- 26669621 TI - Older people's experiences of care in nursing homes: a meta-synthesis. AB - AIM: To integrate the current international knowledge and enhance our understanding of the experiences of older people of being cared for in nursing homes. BACKGROUND: There is a lack of integrated knowledge to help face the challenge of providing care to older people in nursing homes. Understanding the experiences of older people regarding their own care leads to interventions for reducing older people's suffering, while living in nursing homes. METHODS: Keywords describing the experiences of being cared for in nursing homes were used to systematically search electronic databases for qualitative research articles. A meta-synthesis study employing the interpretative meta-ethnography approach devised by Noblit and Hare was carried out to analyse seven qualitative articles identified during the search process. FINDINGS: Seven studies included in this meta-synthesis were published between 2007 and 2015. The experiences of older people of being cared for in nursing homes were expressed by the metaphor 'retaining the meaning of being alive'. Older people wished for a homelike place where they would be delivered care with the consideration of all its humanistic aspects. While conflict between their expectations and organizational demands damaged this sought ideal, adjustment to life conditions and taking an active role led to a feeling of being alive. DISCUSSION: This meta-synthesis integrates our knowledge on organizational and administrative demands, and personal factors influencing the provision of individualized care in nursing homes. LIMITATIONS: The mental functionality of older people that suffer from dementia might impact on their ability to be involved in research and have a 'voice' in terms of their experience of being cared for in nursing homes. CONCLUSION AND IMPLICATIONS FOR NURSING: The institutional character of the nursing home restricts older people's decision-making. The challenge in nursing home care is to balance the tensions between the individual needs and the collective dimensions of care. IMPLICATIONS FOR NURSING POLICY: Nurse policymakers need to consider the ambience in nursing homes, develop a caring culture for the provision of a holistic care to older people and make the nursing home as close to a home as possible. PMID- 26669622 TI - Anseongella ginsenosidimutans gen. nov., sp. nov., isolated from soil cultivating ginseng. AB - A Gram-stain-negative, rod-shaped, non-spore-forming, oxidase and catalase positive, strictly aerobic bacterium, designated strain Gsoil 524T, was isolated from the soil of a ginseng field and subjected to polyphasic taxonomic analysis. Phylogenetic analysis, based on the 16S rRNA gene sequence, placed Gsoil 524T in a distinct lineage in the family Sphingobacteriaceae, sharing 87.2-88.0 % sequence similarity with members of the closely related genera Pedobacter, Mucilaginibacter and Solitalea. Strain Gsoil 524T contained MK-7 as the predominant quinone, and iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 1omega5c as the major fatty acids. Strain Gsoil 524T could be distinguished from the other members of the family Sphingobacteriaceae by a number of chemotaxonomic and phenotypic characteristics. The major polar lipids in strain Gsoil 524T were phosphatidylethanolamine and two unidentified polar lipids. Compared with the standard and reference strains unidentified sphingolipid was also found. Based on this polyphasic taxonomic analysis, strain Gsoil 524T represents a novel species within a novel genus, for which the name Anseongella ginsenosidimutans gen. nov., sp. nov. is proposed. The type strain of Anseongella ginsenosidimutans is Gsoil 524T ( = KACC 14636T = KCTC 22261T = LMG 24494T). PMID- 26669623 TI - A lot is missing: the Orcade study. PMID- 26669624 TI - Spectrofluorimetric determination of thioridazine and flupentixol in dosage forms; application to content uniformity test. AB - A reliable, sensitive, cheap and non-extractive spectrofluorimetric method has been developed and validated for determination of thioridazine and flupentixol based on ternary complex formation with eosin and lead(II) in the presence of methylcellulose as surfactant at pH 3.2. Under the optimum conditions, the quantitative quenching effect of investigated drugs on the native fluorescence of eosin has been investigated. The quenching of the eosin fluorescence was measured at 517 nm after excitation at 462 nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized, and the results were satisfactory. The calibration plots were constructed over the range of 0.5-3.0 ug mL(-1) . The developed method was successfully applied for determination of investigated drugs in commercial tablets without interference from common excipients. It was further applied for content uniformity testing of flupentixol in its tablets. Statistical comparisons of the results with those of the reference methods revealed excellent agreement and indicated no significant difference in accuracy and precision. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669625 TI - H(+)-pyrophosphatase from Salicornia europaea enhances tolerance to low phosphate under salinity in Arabidopsis. AB - Increasing soil salinity threatens crop productivity worldwide. High soil salinity is usually accompanied by the low availability of many mineral nutrients. Here, we investigated the potential role that the H(+)- PPase could play in optimizing P use efficiency under salinity in plants. Transgenic Arabidopsis plants overexpressing either SeVP1 or SeVP2 from Salicornia europaea outperformed the wild-types under low phosphate (Pi) as well as low Pi plus salt conditions. Our results suggested that H(+)-PPase could increase external Pi acquisition through promoting root development and upregulating phosphate transporters, thus to protect plants from Pi limiting stress. This study provides a potential strategy for improving crop yields challenged by the co-occurrence of abiotic stresses. PMID- 26669626 TI - Effects of hamstring stretching on passive muscle stiffness vary between hip flexion and knee extension maneuvers. AB - The purpose of this study was to examine whether the effects of hamstring stretching on the passive stiffness of each of the long head of the biceps femoris (BFl), semitendinosus (ST), and semimembranosus (SM) vary between passive knee extension and hip flexion stretching maneuvers. In 12 male subjects, before and after five sets of 90 s static stretching, passive lengthening measurements where knee or hip joint was passively rotated to the maximal range of motion (ROM) were performed. During the passive lengthening, shear modulus of each muscle was measured by ultrasound shear wave elastography. Both stretching maneuvers significantly increased maximal ROM and decreased passive torque at a given joint angle. Passive knee extension stretching maneuver significantly reduced shear modulus at a given knee joint angle in all of BFl, ST, and SM. In contrast, the stretching effect by passive hip flexion maneuver was significant only in ST and SM. The present findings indicate that the effects of hamstring stretching on individual passive muscles' stiffness vary between passive knee extension and hip flexion stretching maneuvers. In terms of reducing the muscle stiffness of BFl, stretching of the hamstring should be performed by passive knee extension rather than hip flexion. PMID- 26669627 TI - Lawn Structured Triboelectric Nanogenerators for Scavenging Sweeping Wind Energy on Rooftops. AB - A novel triboelectric nanogenerator (TENG) is designed, based on flexible and transparent vertical-strip arrays, for environmental wind-energy harvesting. Given the low cost, simple structure, and wide applicability, the TENGs present a green alternative to traditional methods used for large-scale wind-energy harvesting. PMID- 26669628 TI - Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy. AB - OBJECTIVES: To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach. METHODS: Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief. RESULTS: Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p < 0.00001), dyspareunia (p < 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p < 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching. CONCLUSIONS: For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA. PMID- 26669629 TI - Prenatal administration of vaginal progesterone and frequency of uterine contractions in asymptomatic twin pregnancies. AB - INTRODUCTION: A previous study indicated that progesterone reduces the mean uterine contraction frequency in singleton pregnancy at high risk for preterm birth. The aim of this study was to investigate the effect of vaginal progesterone on the frequency of uterine contractions in twin pregnancies. MATERIAL AND METHODS: This was a secondary analysis of a randomized, double blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. Naturally conceived twin pregnancies with no prior history of preterm delivery, asymptomatic regarding preterm labor, who had undergone uterine contraction frequency monitoring from 24 to 34 weeks and 6 days were included in the study. Comparison of the mean frequency of uterine contractions between the treatment groups was performed. We also examined the influence of cervical length and chorionicity on the mean frequency of uterine contractions according to the group. RESULTS: The final analysis included 166 women in the progesterone and 170 in the placebo group. The baseline characteristics were similar in the two groups. Overall, no difference in the mean frequency of uterine contractions (p = 0.91) was observed between the progesterone (2.54 +/- 3.19) and placebo (2.56 +/- 3.59) groups. Also, no difference in the mean frequency of uterine contractions was observed between the groups in each week between 24 and 34 weeks and 6 days of gestation. Cervical length and chorionicity did not influence the frequency of contractions according to the progesterone or placebo treatment. CONCLUSIONS: Overall, progesterone does not influence the frequency of uterine contractions in twin pregnancies. PMID- 26669630 TI - Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes. AB - AIM: To evaluate the clinical usefulness of maternal serum interleukin-6 for the detection of subclinical chorioamnionitis and in the prediction of the latency period in patients with preterm premature rupture of membrane (PPROM). METHODS: The study group included 60 patients at 24-34 weeks of gestation complaining of PPROM. Laboratory investigations included serial measurements of IL-6, TLC and CRP. Conservative management was carried out till 36 weeks unless delivery was indicated beforehand. The main outcome measures were the latency period and the occurrence of subclinical chorioamnionitis. RESULTS: The mean gestational age at presentation was 30.9 weeks and 35.2 weeks at delivery. The mean IL-6 level at presentation was 4.7 pg/ml. There was no correlation between IL-6 at presentation and the latency period. In addition, those diagnosed as having subclinical chorioamnionitis by placental histopathology had significantly higher levels of IL-6 at delivery. Taking IL-6 level cutoff point of 8.5 pg/ml, histological chorioamnionitis, RDS and NICU admission were significantly higher above that level while neonatal birth weight, Apgar scores at one and five minutes were significantly lower. CONCLUSION: Maternal serum IL-6 at the time of PPROM has no correlation to the latency period while IL-6 levels at the time of delivery have significant correlation to the subclinical chorioamnionitis and neonatal outcome measures. PMID- 26669631 TI - Highly Luminescent Colloidal Nanoplates of Perovskite Cesium Lead Halide and Their Oriented Assemblies. AB - Anisotropic colloidal quasi-two-dimensional nanoplates (NPLs) hold great promise as functional materials due to their combination of low dimensional optoelectronic properties and versatility through colloidal synthesis. Recently, lead-halide perovskites have emerged as important optoelectronic materials with excellent efficiencies in photovoltaic and light-emitting applications. Here we report the synthesis of quantum confined all inorganic cesium lead halide nanoplates in the perovskite crystal structure that are also highly luminescent (PLQY 84%). The controllable self-assembly of nanoplates either into stacked columnar phases or crystallographic-oriented thin-sheet structures is demonstrated. The broad accessible emission range, high native quantum yields, and ease of self-assembly make perovskite NPLs an ideal platform for fundamental optoelectronic studies and the investigation of future devices. PMID- 26669632 TI - Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. AB - BACKGROUND: Transient elastography is a non-invasive method for staging liver fibrosis. The meta-analysis using the hierarchical models to evaluate the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B was rarely reported. AIM: A meta-analysis using the hierarchical models was performed to assess transient elastography for diagnosing and stage liver fibrosis in patients with chronic hepatitis B. METHODS: Electronic databases were searched and studies were identified to assess the diagnostic accuracy of transient elastography in CHB patients for staging fibrosis F >= 2, F >= 3 and F = 4 with liver biopsy as a reference standard. The hierarchical summary receiver operating characteristic curve and the bivariate models were performed to evaluate the diagnostic accuracy of transient elastography, and meta-regression analyses were performed to explore the heterogeneity. The quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of studies. RESULTS: Twenty-seven studies with a total of 4386 patients were included in the meta-analysis. The summary sensitivity of transient elastography for staging fibrosis F >= 2, F >= 3 and F = 4 was 0.806 (95% CI, 0.756-0.847), 0.819 (95% CI, 0.748-0.874) and 0.863 (95% CI, 0.818 0.898), respectively, and the summary specificity was 0.824 (95% CI, 0.761 0.873), 0.866 (95% CI, 0.824-0.899) and 0.875 (95% CI, 0.840-0.903), respectively. The corresponding area under the summary receiver operating characteristic curve was 0.88 (95% CI, 0.85-0.91), 0.91 (95% CI, 0.88-0.93) and 0.93 (95% CI, 0.91-0.95), respectively. Meta-regression showed that patient age contributed to heterogeneity. CONCLUSIONS: Transient elastography performs well to diagnose liver fibrosis in patients with chronic hepatitis B, which may reduce the use of liver biopsy. PMID- 26669633 TI - Prevalence and Correlates of Depression and Drinking Behaviors Among Adolescents and Emerging Adults in a Suburban Emergency Department. AB - BACKGROUND: Both alcohol use and depression are concerning health issues among youth. The Emergency Department (ED) is a critical location to access youth with depressive symptoms and alcohol misuse. OBJECTIVES: To inform future interventions in the ED, this study examined the relationship between drinking behaviors and depressive symptoms among youth seeking ED care. METHODS: Youth ages 14-20 were recruited from a level-1 trauma ED located in the Midwest as part of a larger ongoing study. Participants completed an electronic screening survey, which included assessment of alcohol use, depressive symptoms, and demographic variables. Two logistic regression models were conducted to assess the relationship between depressive symptoms with alcohol consumption and specific alcohol-related consequences. RESULTS: Among 3,659 participants, bivariate analysis indicated that individuals screening positive for depression were more likely to be female, nonwhite, receive public assistance, and report higher scores on both alcohol consumption and alcohol-related consequences. Regression analyses indicated alcohol consumption, inability to stop drinking once starting, and feelings of guilt or remorse after drinking were significantly positively related to screening positive for depression. CONCLUSIONS/IMPORTANCE: Current findings support use of the ED as a location for identifying youth who are experiencing co-morbid alcohol use and depressive symptoms. Future research should focus on the effectiveness of brief intervention in the ED that focuses on the co-occurrence of alcohol misuse and depressive symptoms among youth. PMID- 26669634 TI - Aryl-Alkyl-Lysines: Agents That Kill Planktonic Cells, Persister Cells, Biofilms of MRSA and Protect Mice from Skin-Infection. AB - Development of synthetic strategies to combat Staphylococcal infections, especially those caused by methicillin resistant Staphyloccus aureus (MRSA), needs immediate attention. In this manuscript we report the ability of aryl-alkyl lysines, simple membrane active small molecules, to treat infections caused by planktonic cells, persister cells and biofilms of MRSA. A representative compound, NCK-10, did not induce development of resistance in planktonic cells in multiple passages and retained activity in varying environments of pH and salinity. At low concentrations the compound was able to depolarize and permeabilize the membranes of S. aureus persister cells rapidly. Treatment with the compound not only eradicated pre-formed MRSA biofilms, but also brought down viable counts in bacterial biofilms. In a murine model of MRSA skin infection, the compound was more effective than fusidic acid in bringing down the bacterial burden. Overall, this class of molecules bears potential as antibacterial agents against skin-infections. PMID- 26669635 TI - Effects of Fluroquinolones in Newly Diagnosed, Sputum-Positive Tuberculosis Therapy: A Systematic Review and Network Meta-Analysis. AB - BACKGROUND: Tuberculosis is a major public health problem especially in developing countries, the comparative efficacy and safety of fluroquinolones (FQs) for adult patients with newly diagnosed, sputum-positive tuberculosis remains controversial. We aimed to investigate the benefits and risks of FQs containing (addition/substitution) regimens in this population. METHODS: A network meta-analysis was performed to compare FQs (C: ciprofloxacin; O: ofloxacin; Lo: levofloxacin; M: moxifloxacin; G: gatifloxacin) addition/substitution regimen with standard HRZE regimen (ie isoniazid, rifampicin, pyrazinamide and ethambutol) in newly diagnosed, sputum-positive tuberculosis. Medline, Embase and Cochrane Central Register of Controlled Trials were systematically searched, randomized trials with duration longer than 8 weeks were included. The primary outcome was week-8 sputum negativity, and secondary outcomes included treatment failure, serious adverse events and death from all cause. RESULTS: Twelve studies comprising 6465 participants were included in the network meta-analysis. Lowenstein-Jensen culture method showed that HRZEM (OR 4.96, 95% CI 2.83-8.67), MRZE (OR 1.48, 95% CI 1.19-1.84) and HRZM (OR 1.32, 95% CI 1.08-1.62) had more sputum conversion than HRZE by the eighth week, whereas HRC (OR 0.39, 95% CI 0.19-0.77) and HRZO (OR 0.47, 95% CI 0.24-0.92) were worse than HRZE. Moxifloxacin-containing regimens showed more conversion than HRZE by liquid method at the end of two months. But by the end of treatment, FQs containing regimens didn't show superiority than HRZE on treatment failure. There were no significant differences between any regimens on other outcomes like serious adverse events and all-cause death. CONCLUSION: This comprehensive network meta-analysis showed that compared with HRZE, moxifloxacin-containing regimens could significantly increase sputum conversion by the eighth week for patients with newly diagnosed pulmonary tuberculosis while HRC and HRZO regimens were inferior. But all the FQs-containing regimens did not show superiority in other outcomes (such as treatment failure, serious adverse events and all-cause death). Thus, HRZE is still an effective regimen for this population. Although moxifloxacin-containing regimens have deomonstrated their potential, FQs containing regimens should be used with great caution to avoid widespread FQs resistance worldwide. PMID- 26669637 TI - Managing a cluster outbreak of psittacosis in Belgium linked to a pet shop visit in The Netherlands. AB - In July 2013, a Belgian couple were admitted to hospital because of pneumonia. Medical history revealed contact with birds. Eleven days earlier, they had purchased a lovebird in a pet shop in The Netherlands. The bird became ill, with respiratory symptoms. The couple's daughter who accompanied them to the pet shop, reported similar symptoms, but was travelling abroad. On the suspicion of psittacosis, pharyngeal swabs from the couple were taken and sent to the Belgian reference laboratory for psittacosis. Culture and nested polymerase chain reaction (PCR) tests were positive for the presence of Chlamydia psittaci, and ompA genotyping indicated genotype A in both patients. The patients were treated with doxycycline and the daughter started quinolone therapy; all three recovered promptly. Psittacosis is a notifiable disease in Belgium and therefore local healthcare authorities were informed. They contacted their Dutch colleagues, who visited the pet shop. Seven pooled faecal samples were taken and analysed using PCR by the Dutch national reference laboratory for notifiable animal diseases for the presence of Chlamydia psittaci. Four (57%) samples tested positive, genotyping revealed genotype A. Enquiring about exposure to pet birds is essential when patients present with pneumonia. Reporting to health authorities, even across borders, is warranted to prevent further spread. PMID- 26669638 TI - Comparison of three diagnostic tests in detecting vestibular deficit in patients with peripheral vestibulopathy. AB - OBJECTIVES: This study aimed to evaluate the results of the video head impulse test and of the caloric and rotatory chair tests in patients with dizziness. Agreement between test results was assessed and the best protocol for detecting peripheral vestibulopathy was identified. METHODS: Participants comprised 116 patients, 75 with a peripheral vestibulopathy and 41 with non-peripheral vestibulopathy. The main outcome measures were classified as normal or abnormal according to our laboratory data. RESULTS: Agreement between tests was low. Vestibulopathy testing that required all three results to be abnormal had a sensitivity of 0.547, a specificity of 0.878, and positive and negative predictive values of 0.891 and 0.514, respectively. Vestibulopathy testing that required just one result to be abnormal had a sensitivity of 0.933, a specificity of 0.292, and positive and negative predictive values of 0.701 and 0.705, respectively. CONCLUSION: In peripheral vestibulopathy, there was weak concordance in the assessment of horizontal semicircular canal function among the different tests. However, the video head impulse test had sufficient statistical power to be recommended as the first-line test. PMID- 26669639 TI - Pediatric Intensive Care in PICUs and Adult ICUs: A 2-Year Cohort Study in Finland. AB - OBJECTIVES: To investigate the association between the type of ICU and mortality for children treated at PICUs and adult ICUs. DESIGN: This was a national multicenter cohort study. Data were collected from electronic critical care data management systems at 3 units and from national intensive care registries at 26 units. SETTING: We assessed the incidence of admissions, length of stay at ICUs, main diagnoses, and mortality for children at ICUs. Units were categorized as PICUs or as adult ICUs located at university hospitals or at non-academic central hospitals. PATIENTS: Children younger than 17 years of age treated at ICUs in Finland. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: There were 4,876 admissions from 2009 to 2010, and 98.9% of patients survived until unit discharge. The mean length of stay was 3.0 +/- 7.4 days; 1,395 patients (35%) required mechanical ventilation at PICUs versus 167 (35%) at adult university hospital ICUs versus 79 (19%) at central hospital ICUs (p < 0.001). The odds for mortality in univariate regression analysis were emergency admission (odds ratio, 3.99; 95% CI, 1.82-8.76), cardiovascular (odds ratio, 7.84; 95% CI, 3.49-22.88), gastrointestinal (odds ratio, 5.37; 95% CI, 1.45-19.88), acute infections (odds ratio, 2.83; 95% CI, 1.23-6.48), hematologic/oncologic disease (odds ratio, 10.32; 95% CI, 3.14-33.86), and nonsurgical trauma (odds ratio, 3.53; 95% CI, 1.19-10.41). Treatment at adult ICUs had higher odds of mortality compared with PICUs (university hospital: odds ratio, 3.93; 95% CI, 1.85-8.35 and central hospital: odds ratio, 3.91; 95% CI, 1.69-9.05), adjusted for readmission less than 48 hours after discharge, emergency admission, mechanical ventilation, and diagnostic group. CONCLUSIONS: Pediatric patients treated at PICUs showed lower mortality. Requirement of mechanical ventilation, emergency admission, and readmission less than 48 hours after discharge and cardiovascular, gastrointestinal, acute infections, hematologic/oncologic disease, and nonsurgical trauma were associated with higher risk of mortality. PMID- 26669640 TI - Prevalence of Early Posttraumatic Seizures in Children With Moderate to Severe Traumatic Brain Injury Despite Levetiracetam Prophylaxis. AB - OBJECTIVES: To evaluate the prevalence of early seizures after levetiracetam prophylaxis in children with moderate to severe traumatic brain injury. DESIGN: Prospective observational study. SETTING: Level 1 pediatric trauma center. PATIENTS: We enrolled 34 patients between the ages of 0-18 years with moderate to severe traumatic brain injury admitted to the PICU at a level 1 trauma center who received levetiracetam for early posttraumatic seizure prophylaxis. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the prevalence of early posttraumatic seizures that were defined as clinical seizures within 7 days of injury. In 6 of 34 patients (17%), clinical seizures developed despite levetiracetam prophylaxis. An additional two patients had nonconvulsive seizures. This prevalence is similar to that reported in the literature in this patient population who do not receive seizure prophylaxis (20-53%) and is higher than that in patients who receive phenytoin prophylaxis (2-15%). Patients with early posttraumatic seizures were younger (median age, 4 mo) (p < 0.001) and more likely to have suffered from abusive head trauma (p < 0.0004). CONCLUSIONS: Early clinical posttraumatic seizures occurred frequently in children with moderate to severe traumatic brain injury despite seizure prophylaxis with levetiracetam. Younger children and those with abusive head trauma were at increased risk of seizures. Further studies are needed to evaluate the efficacy of levetiracetam before it is routinely used for seizure prophylaxis in these children, particularly in young children and those who have suffered from abusive head trauma. PMID- 26669641 TI - Transvesical Intra-Abdominal Pressure Measurement in Newborn: What Is the Optimal Saline Volume Instillation? AB - OBJECTIVE: To determine the optimal saline volume bladder instillation to measure intravesical pressure in critically ill newborns weighing less than 4.5 kg, and to establish a reference of intra-abdominal pressure value in this population. DESIGN: Prospective monocentric study. SETTING: Neonatal ICU and PICU. PATIENTS: Newborns, premature or not, weighing less than 4.5 kg who required a urethral catheter. MEASUREMENTS AND MAIN RESULTS: Patients were classified into two groups according to whether they presented a risk factor for intra-abdominal hypertension. Nine intravesical pressure measures per patient were performed after different volume saline instillation. The first one was done without saline instillation and then by increments of 0.5 mL/kg to a maximum of 4 mL/kg. Linear models for repeated measurements of intravesical pressure with unstructured covariance were used to analyze the variation of intravesical pressure measures according to the conditions of measurement (volume instilled). Pairwise comparisons of intravesical pressure adjusted mean values between instillation volumes were done using Tukey tests, corrected for multiple testing to determine an optimal instillation volume. Forty-seven patients with completed measures (nine instillations volumes) were included in the analysis. Mean intravesical pressure values were not significantly different when measured after instillation of 0.5, 1, or 1.5 mL/kg, whereas measures after instillation of 2 mL/kg or more were significantly higher. The median intravesical pressure value in the group without intra-abdominal hypertension risk factor after instillation of 1 mL/kg was 5 mm Hg (2-6 mm Hg). CONCLUSIONS: The optimal saline volume bladder instillation to measure intra-abdominal pressure in newborns weighing less than 4.5 kg was 1 mL/kg. Reference intra-abdominal pressure in this population was found to be 5 mm Hg (2-6 mm Hg). PMID- 26669642 TI - A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass. AB - OBJECTIVES: Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Single-center, double-blinded, placebo-controlled, randomized clinical trial. SETTING: Tertiary center, pediatric cardiovascular ICU. PATIENTS: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). CONCLUSIONS: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted. PMID- 26669643 TI - Nurses' Attitudes Toward Clinical Research: Experience of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials. AB - OBJECTIVES: To understand factors affecting nurses' attitudes toward the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials and association with approach/consent rates. DESIGN: Cross-sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials. SETTING: Study was conducted at 16 of 38 self-selected study sites. SUBJECTS: Pediatric and cardiac intensive care nurses. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement "I am happy to take care of a Therapeutic Hypothermia after Pediatric Cardiac Arrest patient". Associations between perceptions and study approach/consent rates were also explored. Of 2,241 nurses invited, 1,387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p < 0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of Therapeutic Hypothermia After Pediatric Cardiac Arrest compared with those who had not (79% vs 54%; p < 0.001). Of the 754 nurses who cared for a Therapeutic Hypothermia After Pediatric Cardiac Arrest patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r = 0.54; p = 0.04), ICU support (r = 0.61; p = 0.02), and the importance of conducting the trial in children (r = 0.61; p = 0.01). CONCLUSIONS: The majority of nurses had positive perceptions of the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials. Institutional, colleague, and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses believed hypothermia was beneficial had lower consent rates, suggesting that educating nurses on study rationale and equipoise may enhance study participation. PMID- 26669644 TI - Evaluation of Endotoxemia After Pediatric Cardiac Surgery With the Endotoxin Activity Assay: An Exploratory Prospective Cohort Study. AB - OBJECTIVE: Children with congenital heart diseases undergoing surgery with cardiopulmonary bypass are exposed to a high risk of perioperative endotoxemia. The aim of our study was to prospectively evaluate endotoxin assay activity reference levels during the postoperative phase of infants undergoing cardiac surgery for congenital heart disease and to assess their association with perioperative variables and postoperative infections. DESIGN: Prospective exploratory single-center cohort study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Infants undergoing cardiac surgery with cardiopulmonary bypass were enrolled. Exclusion criteria were preoperative suspected or confirmed infection, the need for extracorporeal membrane oxygenation or a ventricular assist device in any perioperative phase, surgery for heart transplantation, and/or urgent surgery. INTERVENTIONS: Serial measurements of endotoxin assay activity were performed at baseline, pediatric cardiac ICU arrival, postoperative day 1 and 2. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were enrolled. Overall, 14 of 25 patients (58%) presented at least one endotoxin assay activity level greater than 0.4 during the study period (normal level is < 0.4). Endotoxin assay activity levels tended to significantly increase from baseline to postoperative day 1 and 2 and from pediatric cardiac ICU arrival to postoperative day 2 (p < 0.0001). Endotoxin assay activity greater than 0.6 predicted Gram-negative infections with a sensitivity of 0.40, a specificity of 0.95, a positive predictive value of 0.66, and a negative predictive value of 0.86. At multivariable regression, endotoxin assay activity on postoperative day 1 resulted independently associated with cardiopulmonary bypass duration, lactate, temperature peak, and vasoactive inotropic score at pediatric cardiac ICU arrival. Children with endotoxin assay activity levels greater than 0.6 (vs all the others) showed a significantly higher median (interquartile) number of ventilation days: 8 (2-39) versus 1.5 (1-3 (p = 0.02). CONCLUSIONS: This exploratory study showed that endotoxin assay activity levels in infants undergoing cardiopulmonary bypass are frequently above 0.4 and peak 24-48 hours after surgery and appear to be associated with perioperative impaired organ perfusion. Endotoxin assay activity is not useful to predict Gram-negative infections. PMID- 26669645 TI - Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation. AB - OBJECTIVES: The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. DESIGN: Retrospective chart review before and after intervention. SETTING: Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. PATIENTS: All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. INTERVENTIONS: Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. MEASUREMENTS AND MAIN RESULTS: Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). CONCLUSIONS: Guideline implementation was successful in reducing targeted broad spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible. PMID- 26669646 TI - Alveolar Dead Space Fraction Discriminates Mortality in Pediatric Acute Respiratory Distress Syndrome. AB - OBJECTIVES: Physiologic dead space is associated with mortality in acute respiratory distress syndrome, but its measurement is cumbersome. Alveolar dead space fraction relies on the difference between arterial and end-tidal carbon dioxide (alveolar dead space fraction = (PaCO2 - PetCO2) / PaCO2). We aimed to assess the relationship between alveolar dead space fraction and mortality in a cohort of children meeting criteria for acute respiratory distress syndrome (both the Berlin 2012 and the American-European Consensus Conference 1994 acute lung injury) and pediatric acute respiratory distress syndrome (as defined by the Pediatric Acute Lung Injury Consensus Conference in 2015). DESIGN: Secondary analysis of a prospective, observational cohort. SETTING: Tertiary care, university affiliated PICU. PATIENTS: Invasively ventilated children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 283 children with pediatric acute respiratory distress syndrome, 266 had available PetCO2. Alveolar dead space fraction was lower in survivors (median 0.13; interquartile range, 0.06-0.23) than nonsurvivors (0.31; 0.19-0.42; p < 0.001) at pediatric acute respiratory distress syndrome onset, but not 24 hours after (survivors 0.12 [0.06-0.18], nonsurvivors 0.14 [0.06-0.25], p = 0.430). Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminated mortality with an area under receiver operating characteristic curve of 0.76 (95% CI, 0.66-0.85; p < 0.001), better than either initial oxygenation index or PaO2/FIO2. In multivariate analysis, alveolar dead space fraction at pediatric acute respiratory distress syndrome onset was independently associated with mortality, after adjustment for severity of illness, immunocompromised status, and organ failures. CONCLUSIONS: Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminates mortality and is independently associated with nonsurvival. Alveolar dead space fraction represents a single, useful, readily obtained clinical biomarker reflective of pulmonary and nonpulmonary variables associated with mortality. PMID- 26669648 TI - Bioaccessibility of provitamin A carotenoids from fruits: application of a standardised static in vitro digestion method. AB - Provitamin A carotenoids (beta-carotene, alpha-carotene, and beta-cryptoxanthin) contribute to the dietary intake of vitamin A and are associated with decreased risk of many chronic diseases. Besides their contents in foods, their bioaccessibility is of great interest since it represents the amount that will be absorbed in the gut. The aim of this study was to adopt, for the first time, the in vitro digestion model suitable for food, proposed in a consensus paper by Minekus et al. (2014), to assess the bioaccessibility of carotenoids from the fruits that are the major contributors to the intake of beta-cryptoxanthin in Spain (orange, tangerine, red pepper, peach, watermelon, and persimmon) and loquat. The highest beta-cryptoxanthin content and the lowest bioaccessibility was found in mandarin and loquat (13331.6 and 929.2 MUg per 100 g respectively), whereas the highest contents of beta-carotene and alpha-carotene were recorded in red pepper (1135.3 and 90.4 MUg per 100 g respectively). The bioaccessibility of beta-cryptoxanthin was similar to that of beta-carotene (0.02-9.8% and 1-9.1%, respectively) and was higher than that of beta-carotene in red pepper, watermelon and peach. alpha-Carotene bioaccessibility ranged between 0% and 4.6%. We discuss the critical factors for comparing our data: the form of the food being analyzed (raw/cooked/previously frozen, in the presence or absence of oil/fat) and the protocol for bioaccessibility assessment. Different food processing techniques may increase carotenoid bioaccessibility compared to raw food. However, given the difficulties encountered when comparing the results of studies on bioaccessibility, it seems logical to propose the application of the previously mentioned standardized in vitro protocol. PMID- 26669647 TI - Limiting and Withdrawing Life Support in the PICU: For Whom Are These Options Discussed? AB - OBJECTIVES: Most deaths in U.S. PICUs occur after a decision has been made to limitation or withdrawal of life support. The objective of this study was to describe the clinical characteristics and outcomes of children whose families discussed limitation or withdrawal of life support with clinicians during their child's PICU stay and to determine the factors associated with limitation or withdrawal of life support discussions. DESIGN: Secondary analysis of data prospectively collected from a random sample of children admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 4, 2011, and April 7, 2013. SETTING: Seven clinical sites affiliated with the Collaborative Pediatric Critical Care Research Network. PATIENTS: Ten thousand seventy-eight children less than 18 years old, admitted to a PICU, and not moribund at admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Families of 248 children (2.5%) discussed limitation or withdrawal of life support with clinicians. By using a multivariate logistic model, we found that PICU admission age less than 14 days, reduced functional status prior to hospital admission, primary diagnosis of cancer, recent catastrophic event, emergent PICU admission, greater physiologic instability, and government insurance were independently associated with higher likelihood of discussing limitation or withdrawal of life support. Black race, primary diagnosis of neurologic illness, and postoperative status were independently associated with lower likelihood of discussing limitation or withdrawal of life support. Clinical site was also independently associated with likelihood of limitation or withdrawal of life support discussions. One hundred seventy-three children (69.8%) whose families discussed limitation or withdrawal of life support died during their hospitalization; of these, 166 (96.0%) died in the PICU and 149 (86.1%) after limitation or withdrawal of life support was performed. Of those who survived, 40 children (53.4%) were discharged with severe or very severe functional abnormalities, and 15 (20%) with coma/vegetative state. CONCLUSIONS: Clinical factors reflecting type and severity of illness, sociodemographics, and institutional practices may influence whether limitation or withdrawal of life support is discussed with families of PICU patients. Most children whose families discuss limitation or withdrawal of life support die during their PICU stay; survivors often have substantial disabilities. PMID- 26669649 TI - Intraoperative Treatment of Fetal Asystole After Endovascular Repair of Aortic Coarctation in a Pregnant Woman with Mitral Stenosis. AB - A G1P0 woman with aortic coarctation and mitral valve stenosis underwent endovascular aortic repair with continuous fetal monitoring during the 20th week of pregnancy. On tracheal extubation, an episode of fetal asystole followed by fetal bradycardia was identified. Ephedrine, nitroglycerin, and terbutaline were administered for intrauterine fetal resuscitation. Subsequently, the patient developed hypertension and pulmonary edema, which were treated with furosemide and noninvasive positive pressure ventilation. The fetal heart rate normalized. We conclude that intraoperative monitoring of a previable fetus may aid in optimizing maternal hemodynamics. Before performing interventional procedures in pregnant women, a multidisciplinary team should discuss the goals of neonatal care should adverse fetal events be detected. PMID- 26669650 TI - A Model for Better Leveraging the Point of Preoperative Assessment: Patients and Providers Look Beyond Operative Indications When Making Decisions. AB - Previous literature on preoperative evaluation focuses on the impact on the day of surgery cancellations and delays; however, the framework of cancellations and delays at the time of the elective outpatient preoperative anesthesia visit has not been categorized. We describe the current model in the preoperative clinic at Brigham and Women's Hospital, examining the pattern of cancellations at the time of this preoperative visit and the framework used for categorizing the issues involved. Looking at this broader framework is important in an era of patient centered care; we seek to identify targets to modify the preoperative assessment and adequately assess and capture the spectrum of issues involved. Elective cases evaluated in the preoperative clinic were reviewed over 10 months. Characteristics of cancelled and noncancelled cases were compared. In-depth analysis of issues related to cancellation was done; 1-year follow-up was completed. Cancellation patterns included categories encompassing clinical, financial, alignment with patient values and goals, compliance, and social issues. The period of preoperative assessment can therefore be leveraged to review a number of domains that can adversely affect surgical outcomes and improve patient-centered care. Also, our framework allows the institution to benchmark these patterns over time; increases in cancellations at the time of the preoperative anesthesia clinic visit for specific categories can prompt an opportunity to examine and improve preoperative workflow. PMID- 26669651 TI - The Impact of a Resident Communication Skills Curriculum on Patients' Experiences of Care. AB - Despite the high impact of lapses in communication skills on patient care, these skills are often not explicitly taught in residency training programs. We implemented a simulation and web-based curriculum in communication for anesthesia residents and used a patient survey adapted from the Four Habits Coding Scheme to detect changes in patient feedback on residents' communication skills after the curricular intervention. Postintervention mean ratings of residents for the overall survey were higher than preintervention mean ratings. Future research will focus on assessing the curriculum's effectiveness and exploring the generalizability of the survey and curriculum. PMID- 26669652 TI - Dermoid Cyst of the Lateral Neck Included Within the Submandibular Gland. AB - Dermoid cysts are benign lesions of congenital origin, and those in the head and neck region are usually present as a midline neck mass. They rarely appear in the lateral neck. This article describes the clinical presentation and histopathologic features of an extremely rare case of lateral dermoid cyst included within the submandibular gland in a 58-year-old man. The etiology of the cyst is also discussed. PMID- 26669653 TI - A tri-serine tri-lactone scaffold for the quantification of citrate in urine. AB - Tri-serine tri-lactone based C3 symmetry fluorescent sensors were synthesized. Citrate is shown to bind to sensors, while displaying an increase in fluorescence intensity for the sensor with thiourea and a quenching for the sensor with sulfonamide. Information-rich responses of the sensors enable us to discriminate structurally similar anions, including mono-, di- and tri-carboxylates with 100% correct classification. A simple two-sensor array enables the determination of the concentration of citrate in urine without any sample preparation with high accuracy (error < 2%). PMID- 26669654 TI - Radiographic Diagnosis of Periapical Status and Quality of Root Canal Fillings in a Saudi Arabian Subpopulation. AB - PURPOSE: To assess the prevalence of apical periodontitis (AP), as determined by orthopantomograms (OPGs), and its correlation with the quality of root fillings and coronal restorations. MATERIALS AND METHODS: This cross-sectional study evaluated a random sample of 193 patients--112 (58%) females and 81 (42%) males- who presented as new patients at the Division of Endodontics. Digital OPGs were independently examined by two reliability-calibrated endodontists. The total number of teeth present, the location of the root canalfilled teeth, and the presence or absence of AP were recorded for each radiograph. The results were statistically analysed using the chi-square test followed by model building using multiple logistic regression. RESULTS: A total of 324 endodontically treated teeth from the 193 selected radiographs were analysed. The mean number of teeth per patient was 25.5 +/- 4.6, with an average of 1.64 root canal treatments per subject. Radiographically detected AP was associated with 190 (58.6%) root canal treated teeth. The logistic model shows that the quality of endodontic treatment (adjusted odds ratio [ORa] = 1.82; 95% confidence interval [CI]: 1.40-3.17), status of coronal restoration (ORa = 1.77; 95% CI: 1.20-2.61) and the type of material used for coronal restorations (ORa = 1.39; 95% CI: 1.03-1.87) were significantly related to the periapical health of the teeth. CONCLUSIONS: The quality of endodontic treatment, status of coronal restoration and the type of coronal restorative material were found to be the most important factors influencing the health of periradicular tissue. PMID- 26669655 TI - Evaluation of Dental Status of Adolescents at Kuwait University Dental Clinic. AB - PURPOSE: This study was designed to evaluate the dental status of adolescents initially presenting at Kuwait University Dental Clinic (KUDC). The purpose of this cross-sectional study was to evaluate (a) the prevalence of unrestored caries dentin among 12- to 16-year-old Kuwaiti residents, (b) the frequency of restorations extending into the inner half of the dentin, and (c) tooth loss pattern among this age group. MATERIALS AND METHODS: Twelve- to 16-year-old patients who attended KUDC during the period January 2009 to December 2012 were included in this study. The total number of patients included in the study was 486; however, only 409 panoramic radiographs were available for evaluation. The Student t-test and one-way ANOVA were used for statistical analysis. RESULTS: The prevalence of unrestored dentin caries among 12- to 16-year-old patients was 52%. The frequency of deep restorations extending into the inner half of the dentin was 33%. Tooth loss was found in 8.0% of the sampled population. The most common missing tooth was the mandibular first molar followed by the mandibular second premolar and the maxillary first molar. There were no statistical differences between Kuwaiti and non-Kuwaiti residents regardless of gender; however, males had a slightly higher DMFT. The DMFT and DMFS values in this study were higher than in other studies. CONCLUSION: Despite the tremendous effort by the Kuwaiti government to improve oral health, comprehensive preventive strategies, dental treatment and maintenance of oral health are still necessary and must be reinforced in this age group. PMID- 26669656 TI - Factors Associated with Oral Health-related Quality of Life in Children and Preadolescents: A Cross-sectional Study. AB - PURPOSE: To evaluate the factors associated with the perceptions of oral health related quality of life (OHRQoL) in children and preadolescents. MATERIALS AND METHODS: 167 students aged 8-14 years were recruited from the public schools of Piracicaba, Brazil. Participants were examined for caries, gingivitis, fluorosis, malocclusions and signs and symptoms of temporomandibular disorders (TMD). OHRQoL was measured using the Brazilian Portuguese version of the Child Perceptions Questionnaire (CPQ 8-10 and 11-14), where higher scores indicate worse OHRQoL. Symptoms of anxiety and depression were evaluated using self-applied questionnaires. Sociodemographic characteristics, dental history and oral hygiene habits were evaluated using a questionnaire. Bivariate and multivariate analyses were used to identify the variables associated with CPQ scores. RESULTS: Higher CPQ 8-10 scores were associated with fluorosis, TMD and symptoms of anxiety and depression. Higher CPQ 11-14 scores were associated with females, TMD and symptoms of anxiety and depression. Younger children (OR=0.32, p<0.05) with signs and symptoms of TMD (OR=4.38, p<0.01) and anxiety (OR=4.97, p<0.001) were more likely to present higher CPQ 8-10 scores. Poor OHRQoL was associated with TMD (OR=4.29, p<0.01) and depressive symptoms (OR=4.50, p<0.001) in preadolescents. CONCLUSIONS: The data indicate that experience of oral diseases and disorders as well as psychological phenomena, such as anxiety and depression, influenced oral health outcomes in this group of children and preadolescents. PMID- 26669657 TI - Pattern of Utilisation of Dental Health Care Among HIV-positive Adult Nigerians. AB - PURPOSE: To determine the pattern of dental care utilisation of people living with HIV (PLHIV). MATERIALS AND METHODS: A cross-sectional questionnaire survey of 239 PLHIV patients in three care centres was done. Information on sociodemographics, dental visit, risk groups, living arrangement, medical insurance and need of dental care was recorded. The EC Clearinghouse and WHO clinical staging was used to determine the stage of HIV/AIDS infection following routine oral examinations under natural daylight. Multivariate logistic regression models were created after adjusting for all the covariates that were statistically significant at univariate/bivariate levels. RESULTS: The majority of subjects were younger than 50 years, about 93% had not seen a dentist before being diagnosed HIV positive and 92% reported no dental visit after contracting HIV. Among nonusers of dental care, 14.3% reported that they wanted care but were afraid to seek it. Other reasons included poor awareness, lack of money and stigmatisation. Multivariate analysis showed that lack of dental care was associated with employment status, living arrangements, educational status, income per annum and presenting with oral symptoms. The area under the receiver operating curve was 84% for multivariate logistic regression model 1, 70% for model 2, 67% for model 3 and 71% for model 4, which means that the predictive power of the models were good. CONCLUSION: Contrary to our expectations, dental utilisation among PLHIV was generally poor among this group of patients. There is serious and immediate need to improve the awareness of PLHIVs in African settings and barriers to dental care utilisation should also be removed or reduced. PMID- 26669658 TI - Interaction of MDM33 with mitochondrial inner membrane homeostasis pathways in yeast. AB - Membrane homeostasis affects mitochondrial dynamics, morphology, and function. Here we report genetic and proteomic data that reveal multiple interactions of Mdm33, a protein essential for normal mitochondrial structure, with components of phospholipid metabolism and mitochondrial inner membrane homeostasis. We screened for suppressors of MDM33 overexpression-induced growth arrest and isolated binding partners by immunoprecipitation of cross-linked cell extracts. These approaches revealed genetic and proteomic interactions of Mdm33 with prohibitins, Phb1 and Phb2, which are key components of mitochondrial inner membrane homeostasis. Lipid profiling by mass spectrometry of mitochondria isolated from Mdm33-overexpressing cells revealed that high levels of Mdm33 affect the levels of phosphatidylethanolamine and cardiolipin, the two key inner membrane phospholipids. Furthermore, we show that cells lacking Mdm33 show strongly decreased mitochondrial fission activity indicating that Mdm33 is critical for mitochondrial membrane dynamics. Our data suggest that MDM33 functionally interacts with components important for inner membrane homeostasis and thereby supports mitochondrial division. PMID- 26669659 TI - Genetic structure of the Newfoundland and Labrador population: founder effects modulate variability. AB - The population of the province of Newfoundland and Labrador (NL) has been a resource for genetic studies because of its historical isolation and increased prevalence of several monogenic disorders. Controversy remains regarding the genetic substructure and the extent of genetic homogeneity, which have implications for disease gene mapping. Population substructure has been reported from other isolated populations such as Iceland, Finland and Sardinia. We undertook this study to further our understanding of the genetic architecture of the NL population. We enrolled 494 individuals randomly selected from NL. Genome wide SNP data were analyzed together with that from 14 other populations including HapMap3, Ireland, Britain and Native American samples from the Human Genome Diversity Project. Using multidimensional scaling and admixture analysis, we observed that the genetic structure of the NL population resembles that of the British population but can be divided into three clusters that correspond to religious/ethnic origins: Protestant English, Roman Catholic Irish and North American aboriginals. We observed reduced heterozygosity and an increased inbreeding coefficient (mean=0.005), which corresponds to that expected in the offspring of third-cousin marriages. We also found that the NL population has a significantly higher number of runs of homozygosity (ROH) and longer lengths of ROH segments. These results are consistent with our understanding of the population history and indicate that the NL population may be ideal for identifying recessive variants for complex diseases that affect populations of European origin. PMID- 26669660 TI - High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood. AB - Acyl-CoA dehydrogenase family, member 9 (ACAD9) mutation is a frequent, usually fatal cause of early-onset cardiac hypertrophy and mitochondrial respiratory chain complex I deficiency in early childhood. We retrospectively studied a series of 20 unrelated children with cardiac hypertrophy and isolated complex I deficiency and identified compound heterozygosity for missense, splice site or frame shift ACAD9 variants in 8/20 patients (40%). Age at onset ranged from neonatal period to 9 years and 5/8 died in infancy. Heart transplantation was possible in 3/8. Two of them survived and one additional patient improved spontaneously. Importantly, the surviving patients later developed delayed-onset neurologic or muscular symptoms, namely cognitive impairment, seizures, muscle weakness and exercise intolerance. Other organ involvement included proximal tubulopathy, renal failure, secondary ovarian failure and optic atrophy. We conclude that ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency. Heart transplantation in children surviving neonatal period should be considered with caution, as delayed-onset muscle and brain involvement of various severity may occur, even if absent prior to transplantation. PMID- 26669663 TI - Estimating time to the most recent common ancestor (TMRCA): comparison and application of eight methods. AB - Investigating how an ancestral population diverges to give rise to distinct subpopulations remains a fundamental pursuit in population genetics. There is broad consensus for the 'Out-of-Africa' hypothesis that states that modern humans arose ~200 000 years ago in Africa and spread throughout the continent ~100 000 years ago. This was followed by several waves of major population dispersals across the globe, although the exact nature of the population divergence remains debatable. Existing methods to estimate population divergence time differ in their methodological frameworks and demographic assumptions, and require different types of genetic data as input. These fundamental differences often result in the methods producing inconsistent estimates of the population divergence time, further confounding attempts to robustly uncover the history of human migration, especially when most population genetic studies do not employ multiple methods to estimate the time to the most recent common ancestor (TMRCA). Here, we chose eight popular methods for estimating TMRCA and evaluated their robustness and accuracy in correctly identifying the true TMRCA through a series of simulations that mimicked different evolutionary scenarios. We subsequently applied all eight methods to estimate the population divergence time between Southeast Asian Malays and South Asian Indians using deep whole-genome sequencing data. PMID- 26669661 TI - Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction. AB - Transmission distortion of disease-causing alleles in long QT syndrome (LQTS) has been reported, suggesting a potential role of KCNQ1 and KCNH2 in reproduction. This study sought to investigate parental transmission in LQTS families according to ethnicity, gene loci (LQT1-3: KCNQ1, KCNH2, and SCN5A) or severity of channel dysfunction. We studied 3782 genotyped members from 679 European and Japanese LQTS families (2748 carriers). We determined grandparental and parental origins of variant alleles in 1903 children and 624 grandchildren, and the grandparental origin of normal alleles in healthy children from 44 three-generation control families. LQTS alleles were more of maternal than paternal origin (61 vs 39%, P<0.001). The ratio of maternally transmitted alleles in LQT1 (66%) was higher than in LQT2 (56%, P<0.001) and LQT3 (57%, P=0.03). Unlike the Mendelian distribution of grandparental alleles seen in control families, variant grandparental LQT1 and LQT2 alleles in grandchildren showed an excess of maternally transmitted grandmother alleles. For LQT1, maternal transmission differs according to the variant level of dysfunction with 68% of maternal transmission for dominant negative or unknown functional consequence variants vs 58% for non-dominant negative and variants leading to haploinsufficiency, P<0.01; however, for LQT2 or LQT3 this association was not significant. An excess of disease-causing alleles of maternal origin, most pronounced in LQT1, was consistently found across ethnic groups. This observation does not seem to be linked to an imbalance in transmission of the LQTS subtype-specific grandparental allele, but to the potential degree of potassium channel dysfunction. PMID- 26669662 TI - Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2). AB - Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation. PMID- 26669664 TI - A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. AB - We report two brothers from a consanguineous couple with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones, probably representing a yet uncharacterized SEMD with laxity and dislocations. This condition has clinical overlap with autosomal dominantly inherited SEMD with joint laxity, leptodactylic type caused by recurrent missense variants in the kinesin family member 22 gene (KIF22). Single-nucleotide polymorphism array analysis and whole-exome sequencing in the two affected siblings revealed a shared homozygous nonsense variant [c.906T>A/p.(Tyr302*)] in EXOC6B as the most likely cause. EXOC6B encodes a component of the exocyst complex required for tethering secretory vesicles to the plasma membrane. As transport of vesicles from the golgi apparatus to the plasma membrane occurs through kinesin motor proteins along microtubule tracks, the function of EXOC6B is linked to KIF22 suggesting a common pathogenic mechanism in skeletal dysplasias with joint laxity and dislocations. PMID- 26669665 TI - Can Treadmill Perturbations Evoke Stretch Reflexes in the Calf Muscles? AB - Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8+/-1.0 degrees , the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms). Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally measure reflexes during treadmill-based clinical gait analysis. PMID- 26669666 TI - Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism. AB - Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV independent pathway to melanoma carcinogenesis and implicated pheomelanin's pro oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin's redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism. PMID- 26669667 TI - Smokeless tobacco consumption impedes metabolic, cellular, apoptotic and systemic stress pattern: A study on Government employees in Kolkata, India. AB - Smokeless tobacco (SLT) remains a threat amongst a large population across the globe and particularly in India. The oral use of tobacco has been implicated to cause physiological stress leading to extreme toxicological challenge. The study included 47 SLT-users and 44 non-users providing a spectrum of pathophysiological, clinico-biochemical, antioxidant parameters, cell cycle progression study of PBMC and morphological changes of red blood cells (RBC). The expressions of p53, p21, Bax, Bcl-2, IL-6, TNF- alpha, Cox-2, iNOS were analyzed from thirteen representative SLT-users and twelve non-users. Difference in CRP, random glucose, serum cholesterol, TG, HLDL-C, LDL-C, VLDL-C, neutrophil count, monocyte count, ESR, SOD (PBMC) and TBARS (RBC membrane) were found to be statistically significant (p < 0.05) between the studied groups. The current study confers crucial insight into SLT mediated effects on systemic toxicity and stress. This has challenged the metabolic condition leading to a rise in the inflammatory status, increased apoptosis and RBC membrane damage. The above findings were substantiated with metabolic, clinical and biochemical parameters. This is possibly the first ever in-depth report and remains an invaluable document on the fatal effects of SLT. PMID- 26669669 TI - Erratum. PMID- 26669668 TI - Total flavonoids of Bidens bipinnata L. ameliorate experimental adjuvant-induced arthritis through induction of synovial apoptosis. AB - BACKGROUND: Bidens bipinnata are widely distributed in China, which have been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of total flavonoids of Bidens pilosa L. (TFB) on adjuvant arthritis (AA) and its possible mechanisms. METHODS: The macroscopic scoring of paw edema, secondary paw swelling, and polyarthritis index were measured. Histological examination of the joints and the serum concentrations of IL-6, IL 1beta, and TNF-alpha were examined. Apoptosis in synovial tissue was detected. The expression of Caspase 3 cleavage, serves as a marker undergoing apoptosis, was confirmed by Western blot. RESULTS: TFB attenuated the severity of arthritis on paw edema, hind paw volume, and polyarthritis index of AA rats, improved the histological status in AA rats as well. TFB can inhibit the production of IL-6, IL-1beta, and TNF-alpha from serum. Clear DNA ladder formation was observed in DNA extraction of synovium from TFB treated AA rats. The number of apoptosis was increased with TFB treatment in TUNEL assay. TFB treatment on AA rats significantly increased the expression of Caspase 3 in synovium. CONCLUSIONS: Our data suggest that TFB has a significant anti-arthritic effect in AA through the induction of apoptosis in synovial. PMID- 26669670 TI - The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients. AB - INTRODUCTION: HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characterized by activation of ER stress/UPR and inflammation, the goal of this study was to assess whether the presence of HLA-B*35 contributes to those characteristics. METHODS: PBMCs were purified from healthy controls (n = 49 HC) and lcSSc patients, (n = 44 with PAH, n = 53 without PAH). PBMCs from each group were stratified for the presence of HLA-B*35. Global changes in gene expression in response to HLA-B*35, HLA-B*8 or empty lentivirus were investigated by microarray analysis in HC PBMCs. Total RNA was extracted and qPCR was performed to measure gene expression. RESULTS: ER stress markers, in particular the chaperones BiP and DNAJB1 were significantly elevated in PBMC samples carrying the HLA-B*35 allele. IL-6 expression was also significantly increased in HLA-B*35 lcSSc PBMCs and positively correlated with ER stress markers. Likewise, HMGB1 was increased in HLA-B*35-positive lcSSc PBMCs. Global gene expression analysis was used to further probe the role of HLA-B*35. Among genes downregulated by HLA-B*35 lentivirus were genes related to complement (C1QB, C1QC), cell cycle (CDNK1A) and apoptosis (Bax, Gadd45). Interestingly, complement genes (C1QC and C1QB) showed elevated expression in lcSSc without PAH, but were expressed at the low levels in lcSSc-PAH. The presence of HLA-B*35 correlated with the decreased expression of the complement genes. Furthermore, HLA-B*35 correlated with decreased expression of cyclin inhibitors (p21, p57) and pro-apoptotic genes (Bax, Gadd45) in lcSSc B35 subjects. FYN, a tyrosine kinase involved in proliferation of immune cells, was among the genes that were positively regulated by HLA-B*35. HLA-B*35 correlated with increased levels of FYN in lcSSc PBMCs. CONCLUSIONS: Our study demonstrates that HLA-B*35 contributes to the dysregulated expression of selected ER stress, inflammation and proliferation related genes in lcSSc patient PBMCs, as well as healthy individuals, thus supporting a pathogenic role of HLA-B*35 in the development of PAH in SSc patients. PMID- 26669671 TI - Familiarity affects other-regarding preferences in pet dogs. AB - Other-regarding preferences are considered to be the foundation of human cooperation. However, the evolutionary origin of this behavior in humans remains poorly understood. So far, comparative studies in primates have led to mixed conclusions probably due to methodological differences relating to both task complexity and the types of control conditions used. Moreover, no clear link between phylogenetic relatedness and prosociality has been found, suggesting that other convergent selection pressures may play a role in the evolution of such behaviors. Here, using one of the cognitively less demanding tasks, we show for the first time, that dogs can behave pro-socially by donating food to a conspecific partner, but only if the partner is familiar. This highlights the importance of considering the social relationships between individuals when testing animals for other-regarding behaviors. Moreover, by including a social control condition, we show that the dogs' prosocial response was not due to a simple social facilitation effect. The current findings support recent proposals that other convergent selection pressures, such as dependence on cooperative activities, rather than genetic relatedness to humans, may shape a species' propensity for other-regarding behaviors. PMID- 26669672 TI - Patent watch: Migraine therapies targeting the CGRP pathway: intellectual property landscape. PMID- 26669674 TI - The right dose for every patient: a key step for precision medicine. AB - Understanding the basis of variability in the response of patients to the dose of a drug and a willingness to vary the dose regimen as well as the choice of drug should be one of the key pillars of precision medicine. PMID- 26669676 TI - Production and Fate of C4 Dihydroxycarbonyl Compounds from Isoprene Oxidation. AB - Isoprene epoxydiols (IEPOX) are formed in high yield as second-generation products of atmospheric isoprene oxidation in pristine (low-NO) environments. IEPOX has received significant attention for its ability to form secondary organic aerosol, but the fate of IEPOX in the gas phase, and those of its oxidation products, remains largely unexplored. In this study, three dihydroxycarbonyl compounds with molecular formula of C4H8O3, putative products of IEPOX oxidation, are synthesized to determine their isomer-specific yields from IEPOX. We find that 3,4-dihydroxy-2-butanone (DHBO) comprises 43% and 36% of the products from cis- and trans-beta-IEPOX, respectively, and is by far the most abundant C4H8O3 dihydroxycarbonyl compound produced by this mechanism. OH is found to react with DHBO with a rate coefficient of 1.10 * 10(-11) cm(3) molecule(-1) s(-1) at 297 K, forming two hydroxydicarbonyl compounds that share the molecular formula C4H6O3 with unitary yield. The results of this study are compared with field observations and used to propose a multigenerational mechanism of IEPOX oxidation. Finally, global simulations using GEOS-Chem, a chemical transport model, show that the C4H8O3 dihydroxycarbonyl compounds and their oxidation products are widespread in the atmosphere and estimate annual global production of C4H8O3 dihydroxycarbonyls to be 54 Tg y(-1), primarily as DHBO. PMID- 26669673 TI - Single-cell analysis tools for drug discovery and development. AB - The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed. PMID- 26669677 TI - HPLC Method for Chemical Fingerprinting of Guggul (Commiphora wightii)- Quantification of E- and Z-Guggulsterones and Detection of Possible Adulterants. AB - A reversed-phase high-performance liquid chromatography method was developed for the chemical fingerprinting of Commiphora wightii gum resin (guggul). This method was also used for the quantification of E- and Z-guggulsterones in different C. wightii gum resin samples. The analysis was conducted on a high-performance liquid chromatography system with a reversed-phase column using a gradient elution comprised of water and acetonitrile with 0.1% acetic acid, and a run time of 50 min at 38 degrees C. The calibration curve of E- and Z-guggulsterones showed good linearity with a standard correlation coefficient >0.999, which is within the established range (0.5-250 ug/mL). Twelve marker compounds were selected and successfully analyzed by this method in 22 C. wightii gum resin samples along with 9 gum resin samples of possible adulterant species. PMID- 26669679 TI - Rejection of Breast Reconstruction Among Lesbian Breast Cancer Patients. AB - PURPOSE: After having breast cancer (BC) and being treated by mastectomy, patients typically struggle with decisions about reconstruction. It is unclear how lesbian-identified women think about breast reconstruction. The purpose of this study was to explore lesbian BC survivors' attitudes toward breast reconstruction. This study represents the first published study to analyze data from a lesbian-specific BC forum to evaluate such attitudes. METHODS: We conducted an inductive thematic analysis of breast reconstruction discussions among individuals who posted to a lesbian-specific online support forum found on breastcancer.org , the largest online support venue for BC survivors. Two hundred fifty-five users posted to the lesbian-specific forum; 53 of these users discussed breast reconstruction and were included in the present analysis. We analyzed a total of 168 posts. RESULTS: Our analysis revealed five important themes related to breast reconstruction attitudes as follows: (1) rejecting being defined by their body image, (2) privileging sensation over appearance, (3) believing that being breastless is protective, (4) perceiving their social context as supportive of nonreconstruction, and (5) feeling pressured by social norms to undergo reconstructive surgery. CONCLUSIONS: Among postings in the lesbian-specific online support forum, attitudes related to the rejection of breast reconstruction were pervasive. Provider communication should be evaluated for heterosexist biases, such as the implication that breast reconstruction should be a part of a normal course of treatment. In addition, providers must acknowledge that breast reconstruction is value laden and the range of viable treatment and construction options, including the decision not to reconstruct, should be presented in a nonbiased neutral way. PMID- 26669678 TI - Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group. AB - Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease. PMID- 26669675 TI - Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS. AB - BACKGROUND: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. METHODS: MOG(35-55) induced EAE in female and male apoE deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. RESULTS: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 3 [IQR 2.0 4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. CONCLUSIONS: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease. PMID- 26669680 TI - Pediatric granulomatous orchitis: Case report and review of the literature. AB - An 11-year-old boy presented with fever and abdominal pain, and was diagnosed with retroperitoneal lymphadenitis. At the same time, a painless right scrotal mass was observed. On imaging the testis and the epididymal mass both had abundant blood flow, although tumor markers were negative. Although the right testis had shrunk after antibiotic treatment, swelling was persistent and incisional biopsy was therefore performed, resulting in diagnosis of granulomatous orchitis (GO). No recurrence was found. In cases of scrotal swelling in both the testis and the epididymis of an older child, it is necessary to consider the possibility of inflammatory GO, and orchiectomy should not be performed without careful consideration. PMID- 26669681 TI - Computational characterisation of the interactions between human ST6Gal I and transition-state analogue inhibitors: insights for inhibitor design. AB - Human beta-galactoside alpha-2,6-sialyltransferase I (hST6Gal I) catalyses the synthesis of sialylated glycoconjugates involved in cell-cell interactions. Overexpression of hST6Gal I is observed in many different types of cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase (ST) inhibitors have been developed based on the natural donor, cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac). Of these, analogues that are structurally similar to the transition state exhibit the highest inhibitory activity. In order to design inhibitors that are readily accessible synthetically and with favourable pharmacokinetic properties, an investigation of the replacement of the charged phosphodiester-linker, present in many ST inhibitors, with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been undertaken. To investigate this, molecular docking and molecular dynamics simulations were performed. These simulations provided an insight into the binding mode of previously reported phosphodiester-linked ST inhibitors and demonstrated that targeting the proposed sialyl acceptor site is a viable option for producing selective inhibitors. The potential for a carbamate- or triazole-linker as an isosteric replacement for the phosphodiester in transition-state analogue ST inhibitors was established using molecular docking. Molecular dynamics simulations of carbamate- and phosphodiester-linked compounds revealed that both classes exhibit consistent interactions with hST6Gal I. Overall, the results obtained from this study provide a rationale for synthetic and biological evaluation of triazole- and carbamate-linked transition-state analogue ST inhibitors as potential new antimetastatic agents. PMID- 26669684 TI - [Warning! Oxygen is just makeup]. PMID- 26669682 TI - Aberrant methylation of the TERT promoter in esophageal squamous cell carcinoma. AB - A recent study indicated that upstream of the transcription start site (UTSS) hypermethylation of the telomerase reverse transcriptase (TERT) gene was associated with tumor progression and poor prognosis in pediatric brain tumors. The potential for methylation-mediated regulation of the UTSS region of the TERT gene in esophageal squamous cell carcinoma (ESCC) has not yet been investigated. Here, TERT methylation was investigated in tumor and paired adjacent non cancerous tissues (ANT) from 185 ESCC patients, and the expression of TERT was investigated in 26 tumors paired with ANTs selected from the same cohort. The methylation level of TERT was analyzed in three different regions: region 1, region 2, and the UTSS region. Comparison and correlation of methylation level and clinical features were analyzed in the abovementioned regions. The results showed that the methylation level of TERT was significantly elevated in the tumor relative to the ANT in ESCC. TERT RNA expression was significantly reduced in primary tumors. Tumor stage was the major determinant of survival. The UTSS region may not be an accessible biomarker for ESCC. PMID- 26669686 TI - Persistent Viral Infections. PMID- 26669685 TI - [Unilateral renal agenesis. New arguments about the genetic relationship between kidney malformations and urolithiasis]. AB - BACKGROUND: In few previous works, it has been reported that hypercalciuria is associated with some types of CAKUT, namely ureteropelvic junction obstruction, vesicoureteral reflux or simple renal cysts. In addition, one higher prevalence of hypercalciuria and/or urolithiasis has been described in their family members compared to the general population. This study was carried out to find out whether children with unilateral renal agenesis (URA) have these features previously described in other CAKUT types. METHODS: In a descriptive and multicenter study we studied the prevalence of hypercalciuria, hypocitraturia and urolithiasis in 67 children (43 males and 24 females) with URA and their families. RESULTS: The two metabolic anomalies that promote stone formation were observed in 26 children (38.8%), distributed as follows: hypercalciuria in 16, hypocitraturia in 9, and both hypercalciuria and hypocitraturia in 1. Eight children (11.9%) suffered renal colic during follow-up. Familial history of urolithiasis was found in 42/67 children (62.7%): in 12 of the first-degree relatives, in 15 of the second degree relatives and in 15 patients both in the first-degree as in their second degree relatives. In contrast, in historic control group, only in 28.1% of families at least one member had urolithiasis. CONCLUSION: Our results show that the prevalence of hypercalciuria and/or hypocitraturia is greater in pediatric patients with URA than in the general population. Likewise, the prevalence of urolithiasis in the families of these children is also higher than that in the general population. PMID- 26669687 TI - Is Achenbach's syndrome a surgical emergency? A systematic review. AB - AIM: The aim of this study is to establish the nature (urgent vs. non-urgent), demographics, presentation and management of Achenbach's syndrome and to formulate an algorithmic approach for their diagnosis and management. MATERIALS AND METHODS: A systematic review and met-aggregation of literature from 1944 to 2015 in English language in MedLine, Embase and Cochrane database were conducted. RESULTS: Achenbach's syndrome is a female-dominant disease with median age of 49.5 years (range 22-76) (age <=60, n = 11/12, 91 %). It presents with unilateral volar discoloration of a finger (100 %). It is associated with pain (n = 7/12, 58. %), edema (n = 7/12, 58 %), and paresthesia (n = 3/12, 25 %). The median time to resolution of symptoms without any intervention was 4 days (range 2-14). CONCLUSION: AS is self-limiting and a non-urgent surgical condition. It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography. An algorithmic approach can avoid hospital admissions, partially unnecessary investigation and assist in patient assurance. PMID- 26669688 TI - Essential bariatric emergencies for the acute care surgeon. AB - Bariatric surgery is the most effective treatment for morbid obesity. Due to the high volume of weight loss procedures worldwide, the general surgeon will undoubtedly encounter bariatric patients in his or her practice. Liberal use of CT scans, upper endoscopy and barium swallow in this patient population is recommended. Some bariatric complications, such as marginal ulceration and dyspepsia, can be effectively treated non-operatively (e.g., proton pump inhibitors, dietary modification). Failure of conservative management is usually an indication for referral to a bariatric surgery specialist for operative re intervention. More serious complications, such as perforated marginal ulcer, leak, or bowel obstruction, may require immediate surgical intervention. A high index of suspicion must be maintained for these complications despite "negative" radiographic studies, and diagnostic laparoscopy performed when symptoms fail to improve. Laparoscopic-assisted gastric band complications are usually approached with band deflation and referral to a bariatric surgeon. However, if acute slippage that results in gastric strangulation is suspected, the band should be removed immediately. This manuscript provides a high-level overview of all essential bariatric complications that may be encountered by the acute care surgeon. PMID- 26669689 TI - Factors associated with quality of life in children with asthma living in Scotland. AB - INTRODUCTION: Asthma affects children's quality of life (QoL) but factors associated with QoL are not well understood. Our hypothesis was that there are factors linked to QoL which are amenable to treatment or environmental modification. METHODS: QoL was ascertained in a study designed to link environmental exposures to asthma outcomes. Univariate and multivariate analysis were used to determine which factors are associated with QoL. RESULTS: There were 553 children with asthma where QoL was determined, mean age 10.3 and 312 (58%) were boys. The median QoL score was 5.9 (interquartile range 4.6, 6.8). In the multivariate model, asthma severity (as evidenced by British Thoracic Society, BTS, treatment step), smoking exposure, socioeconomic status and rhinitis were associated with the QoL score. QoL score was reduced by (i) 30% [95% confidence interval 20, 39] for those on BTS step 4 compared to BTS step 1 treatment (ii) 11% [2, 19] for children with >= two resident smokers with reference to no resident smokers (iii) 3% [1, 5] for each quintile difference in deprivation compared to the most affluent and (iv) 9% [4, 14] for children with rhinitis compared to no rhinitis. CONCLUSIONS: The QoL for children with asthma in the UK is generally good. Clinicians caring children with asthma should consider routinely asking about smoke exposure and hayfever symptoms in addition to assessing asthma control. PMID- 26669690 TI - Processing multi-digit numbers: a translingual eye-tracking study. AB - The present study aimed at investigating the underlying cognitive processes and language specificities of three-digit number processing. More specifically, it was intended to clarify whether the single digits of three-digit numbers are processed in parallel and/or sequentially and whether processing strategies are influenced by the inversion of number words with respect to the Arabic digits [e.g., 43: dreiundvierzig ("three and forty")] and/or by differences in reading behavior of the respective first language. Therefore, English- and German speaking adults had to complete a three-digit number comparison task while their eye-fixation behavior was recorded. Replicating previous results, reliable hundred-decade-compatibility effects (e.g., 742_896: hundred-decade compatible because 7 < 8 and 4 < 9; 362_517: hundred-decade incompatible because 3 < 5 but 6 > 1) for English- as well as hundred-unit-compatibility effects for English- and German-speaking participants were observed, indicating parallel processing strategies. While no indices of partial sequential processing were found for the English-speaking group, about half of the German-speaking participants showed an inverse hundred-decade-compatibility effect accompanied by longer inspection time on the hundred digit indicating additional sequential processes. Thereby, the present data revealed that in transition from two- to higher multi-digit numbers, the homogeneity of underlying processing strategies varies between language groups. The regular German orthography (allowing for letter-by-letter reading) and its associated more sequential reading behavior may have promoted sequential processing strategies in multi-digit number processing. Furthermore, these results indicated that the inversion of number words alone is not sufficient to explain all observed language differences in three-digit number processing. PMID- 26669691 TI - Implicit happiness and sadness are associated with ease and difficulty: evidence from sequential priming. AB - Three experiments tested the hypothesis of implicit associations between happiness and the performance ease concept and between sadness and the performance difficulty concept. All three studies applied a sequential priming paradigm: participants categorized emotion words (Experiment 1) or facial expressions (Experiment 2) as positive or negative or as referring to ease or difficulty (Experiment 3). These targets were preceded by briefly flashed ease- or difficulty-related words or neutral non-words (Experiments 1 and 2) or by happy, sad, or neutral facial expressions (Experiment 3) as primes. As predicted, all three experiments revealed increases in reaction times in the sequential priming task from congruent trials (happiness/ease and sadness/difficulty) over neutral trials to incongruent trials (sadness/ease and happiness/difficulty). The findings provide evidence for implicit associative links of happiness with ease and sadness with difficulty, as posited by the implicit-affect-primes-effort model (Gendolla, Int J Psychophysiol 86:123-135, 2012; Soc Pers Psychol Compass 9:606-619, 2015). PMID- 26669692 TI - Long-term far-transfer effects of working memory training in children with ADHD: a randomized controlled trial. AB - ADHD affects working memory (WM) and other executive functions (EFs) and thereby negatively impacts school performance, clinical symptoms and functional impairment. The main aim of this study was to analyse the efficacy of computerized WM training (CWMT) on EF rating scales. A secondary objective was to assess its efficacy on performance-based measures of EF (PBMEF), learning, clinical symptoms and functional impairment. 66 children with combined-type ADHD between 7 and 12 years of age from the Child and Adolescent Psychiatric Unit (Spain) were included in this randomized, double-blind, placebo-controlled, parallel-group clinical trial. The participants were randomized (1:1) to an experimental group (EG) (CWMT) (n = 36) or a control group (CG) (placebo training). Assessments were conducted at baseline (T0), 1-2 weeks (T1), and 6 months post-intervention (T2) with the administration of EF rating scales, PBMEF, measures of academic achievement, and questionnaires regarding clinical symptoms and functional impairment. Participants, parents, teachers and professionals who performed the cognitive assessments were blinded. Adjusted multiple linear regression analysis showed significant improvements in EF scales-parent version, from T1 to T2, on the metacognition index [p = 0.03, d' = -0.78 (95 % CI -1.28 to -0.27)] and on WM (also significant at T2-T0) and plan/organize subscales. Significant improvements were also noted in EF scales-teacher version, from T0 to T1 and T2, on the metacognitive index [p = 0.05, d' = -0.37 (95 % CI -0.86 to 0.12) T1-T0, p = 0.02, d' = -0.81 (95 % CI -1.31 to -0.30) T2-T0] and on the initiate, WM, monitor and shift subscales. There were also significant improvements in PBMEF, ADHD symptoms, and functional impairment. CWMT had a significant impact on ADHD deficits by achieving long-term far-transfer effects. PMID- 26669693 TI - Influence of a novel, versatile bifunctional chelator on theranostic properties of a minigastrin analogue. AB - BACKGROUND: 6-[Bis(carboxymethyl)amino]-1,4-bis(carboxymethyl)-6-methyl-1,4 diazepane (AAZTA ) is a promising chelator with potential advantages over 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for radiopharmaceutical applications. Its mesocyclic structure enables fast radiolabelling under mild conditions with trivalent metals including not only (68)Ga for positron emission tomography (PET) but also (177)Lu and (111)In for single-photon emission computed tomography (SPECT) and radionuclide therapy. Here, we describe the evaluation of a bifunctional AAZTA derivative conjugated to a model minigastrin derivative as a potential theranostic agent. METHODS: An AAZTA derivative with an aliphatic C9 chain as linker was coupled to a minigastrin, namely [AAZTA(0), D-Glu(1), desGlu(2-6)]-minigastrin (AAZTA-MG), and labelled with (68)Ga, (177)Lu and (111)In. The characterisation in vitro included stability studies in different media and determination of logD (octanol/PBS). Affinity determination (IC50) and cell uptake studies were performed in A431 CCK2R cells expressing the human CCK2 receptor. MUPET/CT and ex vivo biodistribution studies were performed in CCK2 tumour xenograft-bearing nude mice and normal mice. RESULTS: AAZTA-MG showed high radiochemical yields for (68)Ga (>95 %), (177)Lu (>98 %) and (111)In (>98 %). The logD value of -3.7 for both [(68)Ga]- and [(177)Lu]-AAZTA-MG indicates a highly hydrophilic character. Stability tests showed overall high stability in solution with some degradation in human plasma for [(68)Ga]- and transchelation towards DTPA for and [(177)Lu] AAZTA-MG. An IC50 value of 10.0 nM was determined, which indicates a high affinity for the CCK2 receptor. Specific cell uptake after 60 min was >7.5 % for [(68)Ga]-AAZTA-MG and >9.5 % for [(177)Lu]-AAZTA-MG, comparable to other DOTA-MG analogues. MUPET/CT studies in CCK2 receptor tumour xenografted mice not only revealed high selective accumulation in A431-CCK2R positive tumours of (68)Ga labelled AAZTA-MG (1.5 % ID/g in 1 h post injection) but also higher blood levels as corresponding DOTA-analogues. The (111)In-labelled peptide had a tumour uptake of 1.7 % ID/g. Biodistribution in normal mice with the [(177)Lu]-AAZTA-MG showed a considerable uptake in intestine (7.3 % ID/g) and liver (1.5 % ID/g). CONCLUSION: Overall, AAZTA showed interesting properties as bifunctional chelator for peptides providing mild radiolabelling conditions for both (68)Ga and trivalent metals having advantages over the currently used chelator DOTA. Studies are ongoing to further investigate in vivo targeting properties and stability issues and the influence of spacer length on biodistribution of AAZTA. PMID- 26669694 TI - Circadian rhythm influences genome-wide transcriptional responses to (131)I in a tissue-specific manner in mice. AB - BACKGROUND: Circadian variation of gene expression is often neglected when ionizing radiation-induced effects are studied, whether in animal models or in cell culture. This study characterized diurnal variation of genome-wide transcriptional regulation and responses of potential biomarkers and signature genes in normal mouse tissues at 24 h after i.v. administration of (131)I. METHODS: Female BALB/c nude mice were i.v. injected with 90 kBq (131)I at 9:00 a.m., 12:00 p.m., or 3:00 p.m. and killed after 24 h (n = 4/group). Paired control groups were mock-treated (n = 3-4/group). The kidneys, liver, lungs, spleen, and thyroid were excised, snap-frozen, and stored at -80 degrees C until extraction of total RNA. RNA microarray technology was used for genome-wide expression analysis. Enriched biological processes were categorized after cellular function. Signature genes for ionizing radiation and thyroid hormone induced responses were taken from the literature. Absorbed dose was estimated using the Medical Internal Radiation Dose (MIRD) formalism. RESULTS: The thyroid received an absorbed dose of 5.9 Gy and non-thyroid tissues received 0.75-2.2 mGy over 24 h. A distinct peak in the total number of significantly regulated transcripts was observed at 9:00 a.m. in the thyroid, but 3 h later in the kidney cortex, kidney medulla, and liver. Transcriptional regulation in the lungs and spleen was marginal. Associated cellular functions generally varied in quality and response strength between morning, noon, and afternoon. In the thyroid, 25 genes were significantly regulated at all investigated times of day, and 24 thereof showed a distinct pattern of pronounced down-regulation at 9:00 a.m. and comparatively weak up-regulation at later times. Eleven of these genes belonged to the species-specific kallikrein subfamily Klk1b. Responses in signature genes for thyroid hormone-induced responses were more frequent than for ionizing radiation, and trends persisted irrespective of time of day. CONCLUSION: Diurnal variation of genome-wide transcriptional responses to 90 kBq (131)I was demonstrated for the thyroid, kidney cortex and medulla, and liver, whereas variation was only marginal in the lungs and spleen. Overall, significant detection of potential biomarkers and signature genes was validated at each time of day, although direction of regulation and fold-change differed between morning, noon, and afternoon. These findings suggest that circadian rhythm should be considered in radiation research and that biological and analytical endpoints should be validated for circadian robustness. PMID- 26669695 TI - Homogenous VUV advanced oxidation process for enhanced degradation and mineralization of antibiotics in contaminated water. AB - This study was aimed to evaluate the degradation and mineralization of amoxicillin(AMX), using VUV advanced process. The effect of pH, AMX initial concentration, presence of water ingredients, the effect of HRT, and mineralization level by VUV process were taken into consideration. In order to make a direct comparison, the test was also performed by UVC radiation. The results show that the degradation of AMX was following the first-order kinetic. It was found that direct photolysis by UVC was able to degrade 50mg/L of AMX in 50min,while it was 3min for VUV process. It was also found that the removal efficiency by VUV process was directly influenced by pH of the solution, and higher removal rates were achieved at high pH values.The results show that 10mg/L of AMX was completely degraded and mineralized within 50s and 100s, respectively, indicating that the AMX was completely destructed into non-hazardous materials. Operating the photoreactor in contentious-flow mode revealed that 10mg/L AMX was completely degraded and mineralized at HRT values of 120s and 300s. it was concluded that the VUV advanced process was an efficient and viable technique for degradation and mineralization of contaminated water by antibiotics. PMID- 26669696 TI - Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin alphavbeta3-targeting Radiotracer. AB - PURPOSE: To assess the potential utility of an integrin alphavbeta3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. MATERIALS AND METHODS: All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). RESULTS: Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 +/- 3.39 vs 19.01 +/- 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin alphavbeta3 on the activated hepatic stellate cells, and the integrin alphavbeta3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon alpha2b compared with that in the control group (relative liver-to-background ratio: 0.45 +/- 0.05 vs 1.01 +/- 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 +/- 0.06 vs 1.01 +/- 0.05; P < .0001). CONCLUSION: (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis. PMID- 26669697 TI - Normative data for the American Orthopedic Foot and Ankle Society ankle-hindfoot, midfoot, hallux and lesser toes clinical rating system. AB - PURPOSE: Despite some theoretical reservations, the AOFAS clinical rating system with its scales for ankle-hindfoot, midfoot, hallux and lesser toes is one of the most widely used assessment tools in foot and ankle surgery. This study was designed to generate age- and gender-related norm values for all four subscales. METHODS: Despite not being used in a self-administered manner, the AOFAS score underwent cross cultural adaptation to guarantee unrestricted comparability of data. A data pool was generated using the results of personal interviews and clinical examination of 625 individuals, including staff and visitors to our hospital, and excluding people scheduled for foot surgery or in after-treatment. These data served as a basis to calculate all four parts of the AOFAS clinical rating system. RESULTS: Mean value for the ankle-hindfoot scale was calculated as 91.6 points (+/-0.9 confidence interval), and 89.3 points for the midfoot scale (+/-1.0 CI), 88.3 for the hallux metatarsophalangeal-interphalangeal scale (+/- 0.9 CI) and 91.0 for the lesser metatarsophalangeal-interphalangeal scale (+/- 0.8 CI). Results showed a decrease with age in all four scales. Males showed better results than females. Individuals with previous surgery showed lower results in the respective score. CONCLUSIONS: While lowered scoring results prior to surgery reflect the degree of restrictions due to pain, function and alignment problems, post-operative increases in clinical scoring should indicate return to age-related norm values. Our data calculated these norm values for the first time for all four AOFAS scales, giving a basis for better interpretation of published results in foot and ankle surgery. Our data showed and quantified the decrease of norm values with age, especially for hallux and lesser toes scores, as well as lower norm values for females and for individuals that had had surgery of the foot. LEVEL OF EVIDENCE: Level I, diagnostic study. PMID- 26669698 TI - Multi-domain Predictors of Attention Deficit/Hyperactivity Disorder Symptoms in Preschool Children: Cross-informant Differences. AB - Numerous studies indicated that agreement between parent and teacher ratings of symptoms of attention-deficit/hyperactivity disorder in children of all ages is poor, but few studies have examined the factors that may be associated with rater differences. The present study examined the contextual, parent, parenting, and child factors associated with rater differences in a community sample of 4-year old children. Parents and teachers of 344 4-year-olds recruited from preschools and pediatric practices completed the preschool versions of the Child Symptom Inventory. Measures of socioeconomic status, family stress and conflict, caretaker depression, parental hostility, support-engagement, and scaffolding skills, and child negative affect (NA), sensory regulation (SR), effortful control (EC), inhibitory control, and attachment security were obtained either by parental report or observational measures. chi 2 difference tests indicated that child factors of EC and SR, and contextual factor of stress and conflict, contributed more to parent-ratings of ADHD-I and ADHD-HI than to teacher-ratings of those same types of symptoms. Two factors contributed more to teacher-than to parent-rated ADHD-I, NA and caretaker depression. Results indicate there are differences in factors associated with ADHD symptoms at home and school, and have implications for models of ADHD. PMID- 26669699 TI - PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer. AB - Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. PMID- 26669700 TI - Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. AB - Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation. PMID- 26669702 TI - Correction: Gender-specific medicine in the genomic era. PMID- 26669701 TI - Feasibility of a Low-Power Radiofrequency Ablation Protocol to Delay Steam Popping. AB - PURPOSE: Steam popping frequently occurs during conventional high-power radiofrequency (RF) ablation, increasing the risk of tumor spread. The aim of this study was to evaluate the effect of a low-power RF ablation protocol on the intensity and timing of steam popping in ex vivo bovine liver. MATERIALS AND METHODS: High-power (maximum 200 W; group 1) and low-power (maximum 70 W; group 2) RF ablation protocols were established. In the first phase, RF ablation was conducted for 12 min. Ablation volume, intensity, and timing of maximal popping sounds and total energy generated for RF ablation were compared between groups 1 and 2. In the second phase, RF ablation was conducted until maximal popping occurred, and ablation zones on histologic specimens were compared. RESULTS: Relative to group 1, maximal popping occurred at significantly delayed timing in group 2 (50 s +/- 11 vs 397 s +/- 117; P < .001), but without a difference in intensity (ratios vs reference sound of 0.70 +/- 0.18 vs 0.83 +/- 0.26; P = .138). The ablation volume after 12 min of RF ablation did not differ between groups 1 and 2 (18.46 cm(3) +/- 1.35 vs 15.78 cm(3) +/- 0.64; P = .086). However, in the histologic specimens obtained when maximal popping occurred, the area of complete coagulative necrosis was significantly larger in group 2 (P < .05). CONCLUSIONS: Low-power RF ablation delays steam popping while providing comparable therapeutic effects to high-power RF ablation. Delaying maximal popping may prevent tumor cell dispersion because maximal popping occurs after an adequate ablation zone has been achieved. PMID- 26669703 TI - Elevated CO2 enhances photosynthetic efficiency, ion uptake and antioxidant activity of Gynura bicolor DC. grown in a porous-tube nutrient delivery system under simulated microgravity. AB - It is well known that plants can grow under space conditions, however, perturbations of many biological phenomena have been highlighted due to the effect of altered gravity and its possible interaction with other factors (e.g., CO2 , ion radiation, etc. Our aim was to test whether elevated CO2 could provide 'protection' to Gynura bicolor against the damaging effects of simulated microgravity (SM) on photosynthesis, ion uptake and antioxidant activity. As compared to G. bicolor grown in ambient CO2 with no SM (ACO2 ), growth and yield of the plants increased under elevated ambient CO2 with no SM (ECO2 ) and decreased under ACO2 +SM, whereas there was no significant effect on ECO2 +SM. Reductions in the content of Chl a, carotenoids and Chl a+b were 17.9%, 20.7% and 17.9% under ACO2 +SM, respectively, but under ECO2 there was a significant effect on all photosynthetic pigments except Chl b, compared to ACO2 . Photosynthesis was improved under ECO2 with SM and such an improvement was associated with improved water use efficiency and instantaneous carboxylation efficiency. Furthermore, SM caused a reduction in ion absorption rate, except for Ca(2+) , while ECO2 increased the uptake rate. Finally, the activity of SOD, POD and the content of MDA and H2 O2 were enhanced under SM treatments and were highest in ACO2 +SM. In contrast, T-AOC activity and GSH content significantly declined in ACO2 +SM compared to other treatments. These results suggest that ACO2 is not sufficient to counteract SM impact, but the increase is usually caused by improvement in CO2 nutrition in ECO2 +SM in comparison with ACO2 +SM. PMID- 26669704 TI - Goblet cells are involved in translocation of staphylococcal enterotoxin A in the intestinal tissue of house musk shrew (Suncus murinus). AB - AIMS: To elucidate an entry site of staphylococcal enterotoxin A (SEA), which is a major toxin for staphylococcal foodborne poisoning, into gastrointestinal tissue using a house musk shrew model. METHODS AND RESULTS: House musk shrews were per orally administered with recombinant SEA and localization of SEA in gastrointestinal tissues was investigated by immunohistochemistry and immunoelectron microscopy 30 min after administration. SEA was detected in a subset of intestinal epithelial cells and lamina propria in the villi of jejunum and ileum. This observation was also found in gastrointestinal loops. Morphological characteristics of the SEA-immunopositive cells indicated that goblet cells are an entry site of SEA.SEA entered mucus-expelling goblet cells and the induction of mucus secretion by alyll isothiocyanate resulted in an intensive SEA signal. These results suggest that mucus secretion by goblet cells is important for the translocation of SEA. CONCLUSIONS: SEA can translocate across intestinal epithelia via mucus-expelling goblet cells. SIGNIFICANCE AND IMPACTS OF THE STUDY: An entry site of SEA during translocation across the gastrointestinal mucosal barrier was investigated. This study was the first to demonstrate the significance of goblet cells as an entry site of this bacterial toxin. PMID- 26669705 TI - A SERS-based lateral flow assay biosensor for highly sensitive detection of HIV-1 DNA. AB - User-friendly lateral flow (LF) strips have been extensively used for point-of care (POC) self-diagnostics, but they have some limitations in their detection sensitivity and quantitative analysis because they only identify the high cut-off value of a biomarker by utilizing color changes that are detected with the naked eye. To resolve these problems associated with LF strips, we developed a novel surface-enhanced Raman scattering (SERS)-based LF assay for the quantitative analysis of a specific biomarker in the low concentration range. Herein, human immunodeficiency virus type 1 (HIV-1) DNA was chosen as the specific biomarker. Raman reporter-labeled gold nanoparticles (AuNPs) were employed as SERS nano tags for targeting and detecting the HIV-1 DNA marker, as opposed to using bare AuNPs in LF strips. It was possible to quantitatively analyze HIV-1 DNA with high sensitivity by monitoring the characteristic Raman peak intensity of the DNA conjugated AuNPs. Under optimized conditions, the detection limit of our SERS based lateral flow assay was 0.24 pg/mL, which was at least 1000 times more sensitive compared to colorimetric or fluorescent detection methods. These results demonstrate the potential feasibility of the proposed SERS-based lateral flow assay to quantitatively detect a broad range of genetic diseases with high sensitivity. PMID- 26669706 TI - Anatomical variants of lower limb vasculature and implications for free fibula flap: Systematic review and critical analysis. AB - Sound knowledge of the anatomical patterns of lower limb vasculature is crucial for raising the free fibula flap (FFF). The tibial arteries are particularly susceptible to anatomical variations with a dominant role of peroneal artery (PR) for lower leg perfusion, and hence precluding fibular flap harvest. In this systematic review we study the prevalence of lower limbs with dominant peroneal artery (dPR). A systematic review of the MEDLINE and EMBASE databases was conducted using a comprehensive combination of keywords and search algorithm according to PRISMA guidelines. Articles describing the branching patterns of lower limb arteries, in cadaveric or angiographic studies, were included. A total of 5,790 limbs were included from 26 studies. dPR was found in 5.2% of all limbs. The combination of dPR with hypoplastic or aplastic posterior tibial artery was the most common pattern (3.3%) followed by hypoplastic anterior tibial artery (1.5%). Peronea arteria magna (PAM) was seen in 0.4% of limbs. Bilateral variants were seen in 20% of all cases with a dPR. A greater awareness of dPR as anatomical variation and its prevalence among healthy subjects can prevent ischemic donor-site complications after FFF harvest. Clinical examination alone may not suffice to detect anatomical variations, hence preoperative imaging of lower limb vascular system is recommended. PMID- 26669707 TI - Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation. AB - In this study, we described the design, synthesis, and biological evaluation of 1,3-diaryl-pyridones as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The 1,3-diaryl-pyridones were synthesized via Chan-Lam and Suzuki coupling reactions. Two representative compounds, 17 and 35h, displayed excellent enzymatic inhibitory activities, with IC50 values of 3.5 and 3.0 nm, respectively. Furthermore, compounds 17 and 35h blocked the tube formation and suppressed the VEGF-induced phosphorylation of VEGFR-2 and downstream extracellular signal-regulated kinases (Erk) in human umbilical vein endothelial cells (HUVECs) at 10 nm concentration. The docking simulation showed that compound 17 bound well into the active site of VEGFR-2 via two hydrogen bonds and hydrophobic interactions. PMID- 26669708 TI - Comparison of classification methods in breath analysis by electronic nose. AB - Currently, many different methods are being used for pre-processing, statistical analysis and validation of data obtained by electronic nose technology from exhaled air. These various methods, however, have never been thoroughly compared. We aimed to empirically evaluate and compare the influence of different dimension reduction, classification and validation methods found in published studies on the diagnostic performance in several datasets. Our objective was to facilitate the selection of appropriate statistical methods and to support reviewers in this research area. We reviewed the literature by searching Pubmed up to the end of 2014 for all human studies using an electronic nose and methodological quality was assessed using the QUADAS-2 tool tailored to our review. Forty-six studies were evaluated regarding the range of different approaches to dimension reduction, classification and validation. From forty-six reviewed articles only seven applied external validation in an independent dataset, mostly with a case control design. We asked their authors to share the original datasets with us. Four of the seven datasets were available for re-analysis. Published statistical methods for eNose signal analysis found in the literature review were applied to the training set of each dataset. The performance (area under the receiver operating characteristics curve (ROC-AUC)) was calculated for the training cohort (in-set) and after internal validation (leave-one-out cross validation). The methods were also applied to the external validation set to assess the external validity of the performance. Risk of bias was high in most studies due to non random selection of patients. Internal validation resulted in a decrease in ROC AUCs compared to in-set performance: -0.15,-0.14,-0.1,-0.11 in dataset 1 through 4, respectively. External validation resulted in lower ROC-AUC compared to internal validation in dataset 1 (-0.23) and 3 (-0.09). ROC-AUCs did not decrease in dataset 2 (+0.07) and 4 (+0.04). No single combination of dimension reduction and classification methods gave consistent results between internal and external validation sets in this sample of four datasets. This empirical evaluation showed that it is not meaningful to estimate the diagnostic performance on a training set alone, even after internal validation. Therefore, we recommend the inclusion of an external validation set in all future eNose projects in medicine. PMID- 26669710 TI - "Omics" of High Altitude Biology: A Urinary Metabolomics Biomarker Study of Rats Under Hypobaric Hypoxia. AB - High altitude medicine is an emerging subspecialty that has crosscutting relevance for 21(st) century science and society: from sports medicine and aerospace industry to urban and rural communities living in high altitude. Recreational travel to high altitude has also become increasingly popular. Rarely has the biology of high altitude biology been studied using systems sciences and omics high-throughput technologies. In the present study, 1H-NMR-based metabolomics, along with multivariate analyses, were employed in a preclinical rat model to characterize the urinary metabolome under hypobaric hypoxia stress. Rats were exposed to simulated altitude of 6700 m above the sea level. The urine samples were collected from pre- and post-exposure (1, 3, 7, and 14 days) of hypobaric hypoxia. Metabolomics urinalysis showed alterations in TCA cycle metabolites (citrate, alpha-ketoglutarate), cell membrane metabolism (choline), gut micro-flora metabolism (hippurate, phenylacetylglycine), and others (N-acetyl glutamate, creatine, taurine) in response to hypobaric hypoxia. Taurine, a potential biomarker of hepatic function, was elevated after 3 days of hypobaric hypoxia, which indicates altered liver functioning. Liver histopathology confirmed the damage to tissue architecture due to hypobaric hypoxia. The metabolic pathway analysis identified taurine metabolism and TCA as important pathways that might have contributed to hypobaric hypoxia-induced pathophysiology. This study demonstrates the use of metabolomics as a promising tool for discovery and understanding of novel biochemical responses to hypobaric hypoxia exposure, providing new insight in the field of high altitude medicine and the attendant health problems that occur in response to high altitude. The findings reported here also have potential relevance for sports medicine and aviation sciences. PMID- 26669711 TI - Rise of Microbial Culturomics: Noncontiguous Finished Genome Sequence and Description of Beduini massiliensis gen. nov., sp. nov. AB - Microbial culturomics is a new field of omics sciences that examines the bacterial diversity of human gut coupled with a taxono-genomic strategy. Using microbial culturomics, we report here for the first time a novel Gram negative, catalase- and oxidase-negative, strict anaerobic bacilli named Beduini massiliensis gen. nov., sp nov. strain GM1 (= CSUR P1440 = DSM 100188), isolated from the stools of a female nomadic Bedouin from Saudi Arabia. With a length of 2,850,586 bp, the Beduini massiliensis genome exhibits a G + C content of 35.9%, and contains 2819 genes (2744 protein-coding and 75 RNA genes including 57 tRNA and 18 rRNA genes). It is composed of 6 scaffolds (composed of 6 contigs). A total of 1859 genes (67.75%) were assigned a putative function (by COGs or by NR blast). At least 1457 (53%) orthologous proteins were not shared with the closest phylogenetic species. 274 genes (10.0%) were identified as ORFans. These results show that microbial culturomics can dramatically improve the characterization of the human microbiota repertoire, deciphering new bacterial species and new genes. Further studies will clarify the geographic specificity and the putative role of these new microbes and their related functional genetic content in health and disease. Microbial culturomics is an emerging frontier of omics systems sciences and integrative biology and thus, warrants further consideration as part of the postgenomics methodology toolbox. PMID- 26669712 TI - P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR*28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects. AB - CYP2C9 enzyme contributes to the metabolism of several pharmaceuticals and xenobiotics and yet displays large person-to-person and interethnic variation. Understanding the mechanisms of CYP2C9 variation is thus of immense importance for personalized medicine and rational therapeutics. A genetic variant of P450 (cytochrome) oxidoreductase (POR), a CYP450 redox partner, is reported to influence CYP2C9 metabolic activity in vitro. We investigated the impact of a common variant, POR*28, on CYP2C9 metabolic activity in humans. 148 healthy Swedish and 146 healthy Korean volunteers were genotyped for known CYP2C9 defective variant alleles (CYP2C9*2, *3). The CYP2C9 phenotype was determined using a single oral dose of 50 mg losartan. Excluding oral contraceptive (OC) users and carriers of 2C9*2 and *3 alleles, 117 Korean and 65 Swedish were genotyped for POR*5, *13 and *28 using Taqman assays. The urinary losartan to its metabolite E-3174 metabolic ratio (MR) was used as an index of CYP2C9 metabolic activity. The allele frequency of the POR*28 variant allele in Swedes and Koreans was 29% and 44%, respectively. POR*5 and *13 were absent in both study populations. Considering the CYP2C9*1/*1 genotypes only, the CYP2C9 metabolic activity was 1.40-fold higher in carriers of POR*28 allele than non-carriers among Swedes (p = 0.02). By contrast, no influence of the POR*28 on CYP2C9 activity was found in Koreans (p = 0.68). The multivariate analysis showed that ethnicity, POR genotype, and smoking were strong predictors of CYP2C9 MR (p < 0.05). This is the first report to implicate the importance of POR*28 genetic variation for CYP2C9 metabolic activity in humans. These findings contribute to current efforts for global personalized medicine and using medicines by taking into account pharmacogenetic and phenotypic variations. PMID- 26669709 TI - Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies? AB - Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine. PMID- 26669713 TI - Plant Omics: Isolation, Identification, and Expression Analysis of Cytochrome P450 Gene Sequences from Coleus forskohlii. AB - The omics analyses of plants and the agrigenomics field offer the opportunity to better characterize our ecosystems. In this context, characterization of cytochrome P450 genes (CYP450s), which constitute one of the largest gene families in plants, is important. They play vital roles in biosynthesis of secondary metabolites, phytohormones as well as in detoxification of harmful chemicals. Tuberous roots of Coleus forskohlii accumulate forskolin, a potent and reversible activator of adenylate cyclase, as well as other related diterpenoids. Coleus forskohlii is also known to produce rosmarinic acid, genkwanin (7-O methylapigenin), and guaiacol glycerin. We report here the isolation of CYP450s from C. forskohlii, expression profiling of CYP450s in different tissues, and how different elicitors/stresses regulate the expression of different CYP450 sequences. Degenerate primers, designed from the conserved regions of CYP450s, were used to amplify fragments from cDNA of C. forskohlii and a library was prepared. Sequences homologous to CYP450s were assembled into seven distinct gene fragments (CfP450C1-C7), belonging to seven CYP450 families. Expression profiling of CYP450s showed that the transcripts of CfP450C1, CfP450C4, CfP450C5, CfP450C6, and CfP450C7 were prominent in aerial tissues (flower, young leaf, and mature leaf), whereas expression of CfP450C3 was dominant in root and root tip. CfP450C2 showed higher expression in flowers and roots as compared to other tissues. Expression profiles of CYP450s, in response to different stresses (abscisic acid, methyl jasmonate, salicylic acid, 2, 4-dichloro-phenoxyacetic acid, UVA, and wounding) were also studied. This study has isolated CYP450s from C. forskohlii, and will help to understand their regulation as well as their functions. This is the first report on the isolation and expression analysis of CYP450s from this herb. PMID- 26669714 TI - In reference to "Preliminary development of an ultrabrief two-item bedside test for delirium.". PMID- 26669715 TI - Multiplexed Recombinase Polymerase Amplification Assay To Detect Intestinal Protozoa. AB - This work describes a proof-of-concept multiplex recombinase polymerase amplification (RPA) assay with lateral flow readout that is capable of simultaneously detecting and differentiating DNA from any of the diarrhea-causing protozoa Giardia, Cryptosporidium, and Entamoeba. Together, these parasites contribute significantly to the global burden of diarrheal illness. Differential diagnosis of these parasites is traditionally accomplished via stool microscopy. However, microscopy is insensitive and can miss up to half of all cases. DNA based diagnostics such as polymerase chain reaction (PCR) are far more sensitive; however, they rely on expensive thermal cycling equipment, limiting their availability to centralized reference laboratories. Isothermal DNA amplification platforms, such as the RPA platform used in this study, alleviate the need for thermal cycling equipment and have the potential to broaden access to more sensitive diagnostics. Until now, multiplex RPA assays have not been developed that are capable of simultaneously detecting and differentiating infections caused by different pathogens. We developed a multiplex RPA assay to detect the presence of DNA from Giardia, Cryptosporidium, and Entamoeba. The multiplex assay was characterized using synthetic DNA, where the limits-of-detection were calculated to be 403, 425, and 368 gene copies per reaction of the synthetic Giardia, Cryptosporidium, and Entamoeba targets, respectively (roughly 1.5 orders of magnitude higher than for the same targets in a singleplex RPA assay). The multiplex assay was also characterized using DNA extracted from live parasites spiked into stool samples where the limits-of-detection were calculated to be 444, 6, and 9 parasites per reaction for Giardia, Cryptosporidium, and Entamoeba parasites, respectively. This proof-of-concept assay may be reconfigured to detect a wide variety of targets by re-designing the primer and probe sequences. PMID- 26669716 TI - Immunocytochemical heterogeneity of somatostatin-expressing GABAergic interneurons in layers II and III of the mouse cingulate cortex: A combined immunofluorescence/design-based stereologic study. AB - Many neurological diseases including major depression and schizophrenia manifest as dysfunction of the GABAergic system within the cingulate cortex. However, relatively little is known about the properties of GABAergic interneurons in the cingulate cortex. Therefore, we investigated the neurochemical properties of GABAergic interneurons in the cingulate cortex of FVB-Tg(GadGFP)45704Swn/J mice expressing green fluorescent protein (GFP) in a subset of GABAergic interneurons (GFP-expressing inhibitory interneurons [GINs]) by means of immunocytochemical and design-based stereologic techniques. We found that GINs represent around 12% of all GABAergic interneurons in the cingulate cortex. In contrast to other neocortical areas, GINs were only found in cortical layers II and III. More than 98% of GINs coexpressed the neuropeptide somatostatin (SOM), but only 50% of all SOM + neurons were GINs. By analyzing the expression of calretinin (CR), calbindin (CB), parvalbumin, and various neuropeptides, we identified several distinct GIN subgroups. In particular, we observed coexpression of SOM with CR and CB. In addition, we found neuropeptide Y expression almost exclusively in those GINs that coexpressed SOM and CR. Thus, with respect to the expression of calcium-binding proteins and neuropeptides, GINs are surprisingly heterogeneous in the mouse cingulate cortex, and the minority of GINs express only one marker protein or peptide. Furthermore, our observation of overlap between the SOM + and CR + interneuron population was in contrast to earlier findings of non overlapping SOM + and CR + interneuron populations in the human cortex. This might indicate that findings in mouse models of neuropsychiatric diseases may not be directly transferred to human patients. J. Comp. Neurol. 524:2281-2299, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26669717 TI - QSAR Modeling and Prediction of Drug-Drug Interactions. AB - Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year. As up to 30% of all ADRs are believed to be caused by drug-drug interactions (DDIs), typically mediated by cytochrome P450s, possibilities to predict DDIs from existing knowledge are important. We collected data from public sources on 1485, 2628, 4371, and 27,966 possible DDIs mediated by four cytochrome P450 isoforms 1A2, 2C9, 2D6, and 3A4 for 55, 73, 94, and 237 drugs, respectively. For each of these data sets, we developed and validated QSAR models for the prediction of DDIs. As a unique feature of our approach, the interacting drug pairs were represented as binary chemical mixtures in a 1:1 ratio. We used two types of chemical descriptors: quantitative neighborhoods of atoms (QNA) and simplex descriptors. Radial basis functions with self-consistent regression (RBF-SCR) and random forest (RF) were utilized to build QSAR models predicting the likelihood of DDIs for any pair of drug molecules. Our models showed balanced accuracy of 72-79% for the external test sets with a coverage of 81.36-100% when a conservative threshold for the model's applicability domain was applied. We generated virtually all possible binary combinations of marketed drugs and employed our models to identify drug pairs predicted to be instances of DDI. More than 4500 of these predicted DDIs that were not found in our training sets were confirmed by data from the DrugBank database. PMID- 26669718 TI - Vaccines Combined with Immune Checkpoint Antibodies Promote Cytotoxic T-cell Activity and Tumor Eradication. AB - We demonstrate that a poly(lactide-co-glycolide) (PLG) cancer vaccine can be used in combination with immune checkpoint antibodies, anti-CTLA-4 or anti-PD-1, to enhance cytotoxic T-cell (CTL) activity and induce the regression of solid B16 tumors in mice. Combination therapy obviated the need for vaccine boosting and significantly skewed intratumoral reactions toward CTL activity, resulting in the regression of B16 tumors up to 50 mm(2) in size and 75% survival rates. These data suggest that combining material-based cancer vaccines with checkpoint antibodies has the potential to mediate tumor regression in humans. PMID- 26669720 TI - Photoluminescence and thermoluminescence characteristics of Sr3 B2 O6 :Eu(2+) yellow phosphor. AB - Sr3 B2 O6 :Eu(2+) yellow phosphor was prepared by the combustion method. The crystalline structure, photoluminescence and thermoluminescence properties of Sr3 B2 O6 :Eu(2+) were investigated extensively. The X-ray diffraction result indicates that the Sr3 B2 O6 :Eu(2+) phosphor exhibited a rhombohedral crystal structure. The emission spectra under a 435 nm excited wavelength showed an intense broad band peaking at 574 nm, which corresponds to the 4f(6) 5d(1) -> 4f(7) transition of Eu(2+) ion. There were two different sites of Sr replaced by Eu in host lattice. The concentration quenching process between Eu(2+) ions is determined and the corresponding concentration quenching mechanism was verified as dipole-quadrupole interaction. The glow curve under 3 Gy beta- ray irradiation had the glow peak at 160 degrees C and the average activation energy was defined as about 0.98 eV. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669719 TI - Mitochondrial disease genes COA6, COX6B and SCO2 have overlapping roles in COX2 biogenesis. AB - Biogenesis of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain, is a complex process facilitated by several assembly factors. Pathogenic mutations were recently reported in one such assembly factor, COA6, and our previous work linked Coa6 function to mitochondrial copper metabolism and expression of Cox2, a copper-containing subunit of CcO. However, the precise role of Coa6 in Cox2 biogenesis remained unknown. Here we show that yeast Coa6 is an orthologue of human COA6, and like Cox2, is regulated by copper availability, further implicating it in copper delivery to Cox2. In order to place Coa6 in the Cox2 copper delivery pathway, we performed a comprehensive genetic epistasis analysis in the yeast Saccharomyces cerevisiae and found that simultaneous deletion of Coa6 and Sco2, a mitochondrial copper metallochaperone, or Coa6 and Cox12/COX6B, a structural subunit of CcO, completely abrogates Cox2 biogenesis. Unlike Coa6 deficient cells, copper supplementation fails to rescue Cox2 levels of these double mutants. Overexpression of Cox12 or Sco proteins partially rescues the coa6Delta phenotype, suggesting their overlapping but non-redundant roles in copper delivery to Cox2. These genetic data are strongly corroborated by biochemical studies demonstrating physical interactions between Coa6, Cox2, Cox12 and Sco proteins. Furthermore, we show that patient mutations in Coa6 disrupt Coa6-Cox2 interaction, providing the biochemical basis for disease pathogenesis. Taken together, these results place COA6 in the copper delivery pathway to CcO and, surprisingly, link it to a previously unidentified function of CcO subunit Cox12 in Cox2 biogenesis. PMID- 26669721 TI - Gaetbulibacter aquiaggeris sp. nov., a member of the Flavobacteriaceae isolated from seawater. AB - A Gram-stain-negative, non-flagellated, non-gliding and rod-shaped bacterial strain, designated KEM-8T, was isolated from seawater in the Korean peninsula. Strain KEM-8T was found to grow optimally at pH 7.0-8.0, at 30 degrees C and in the presence of 2-3 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain KEM-8T falls within the clade comprising species of the genus Gaetbulibacter, clustering with the type strains of Gaetbulibacter marinus and Gaetbulibacter lutimaris with which it exhibits 98.4 and 97.2 % 16S rRNA gene sequence similarity, respectively. Sequence similarities to Gaetbulibacter saemankumensis SMK-12T and Gaetbulibacter aestuarii KCTC 23303T were 95.4 and 95.2 %, respectively. Strain KEM-8T was found to contain MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C17 : 0 3-OH, iso-C16 : 0 3-OH and iso-C15 : 1 G as the major fatty acids. The major polar lipids were identified as phosphatidylethanolamine and an unidentified lipid. The DNA G+C content of strain KEM-8T was 36.0 mol% and mean DNA-DNA relatedness values with G. marinus KCTC 23046T and G. lutimaris D1-y4T were 27.6 +/- 0.9 and 10.3 +/- 1.4 %, respectively. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain KEM-8T is distinguishable from species of the genus Gaetbulibacter with validly published names. On the basis of the data presented, strain KEM-8T represents a novel species of the genus Gaetbulibacter, for which the name Gaetbulibacter aquiaggeris sp. nov. is proposed. The type strain is KEM-8T ( = KCTC 42198T = NBRC 110553T). PMID- 26669722 TI - Tracking the Global Distribution of Persistent Organic Pollutants Accounting for E-Waste Exports to Developing Regions. AB - Elevated concentrations of various industrial-use Persistent Organic Pollutants (POPs), such as polychlorinated biphenyls (PCBs), have been reported in some developing areas in subtropical and tropical regions known to be destinations of e-waste. We used a recent inventory of the global generation and exports of e waste to develop various global scale emission scenarios for industrial-use organic contaminants (IUOCs). For representative IUOCs (RIUOCs), only hypothetical emissions via passive volatilization from e-waste were considered whereas for PCBs, historical emissions throughout the chemical life-cycle (i.e., manufacturing, use, disposal) were included. The environmental transport and fate of RIUOCs and PCBs were then simulated using the BETR Global 2.0 model. Export of e-waste is expected to increase and sustain global emissions beyond the baseline scenario, which assumes no export. A comparison between model predictions and observations for PCBs in selected recipient regions generally suggests a better agreement when exports are accounted for. This study may be the first to integrate the global transport of IUOCs in waste with their long-range transport in air and water. The results call for integrated chemical management strategies on a global scale. PMID- 26669723 TI - A maize death acid, 10-oxo-11-phytoenoic acid, is the predominant cyclopentenone signal present during multiple stress and developmental conditions. AB - Recently we investigated the function of the 9-lipoxygenase (LOX) derived cyclopentenones 10-oxo-11-phytoenoic acid (10-OPEA) and 10-oxo-11,15-phytodienoic acid (10-OPDA) and identified their C-14 and C-12 derivatives. 10-OPEA accumulation is elicited by fungal and insect attack and acts as a strong inhibitor of microbial and herbivore growth. Although structurally similar, comparative analyses between 10-OPEA and its 13-LOX analog 12-oxo-phytodienoic acid (12-OPDA) demonstrate specificity in transcript accumulation linked to detoxification, secondary metabolism, jasmonate regulation, and protease inhibition. As a potent cell death signal, 10-OPEA activates cysteine protease activity leading to ion leakage and apoptotic-like DNA fragmentation. In this study we further elucidate the distribution, abundance, and functional roles of 10-OPEA, 10-OPDA, and 12-OPDA, in diverse organs under pathogen- and insect related stress. PMID- 26669724 TI - Ultraselective Gas Separation by Nanoporous Metal-Organic Frameworks Embedded in Gas-Barrier Nanocellulose Films. AB - Metal-organic frameworks (MOFs) are synthesized at carboxy groups on crystalline TEMPO-oxidized cellulose nanofibers (TOCNs). MOF-TOCN films coated on a paper filter have a hierarchical structure from the nano- to macroscale, and demonstrate a high CO2 /CH4 selectivity, over 120 for CO2 at a high gas flux, by the combination of the nanoporous MOFs and the gas-barrier TOCNs, which have strong affinity with each other. PMID- 26669725 TI - Rapid hepatic perfusion decellularization: technique and critique. AB - BACKGROUND: Organ shortage facing the increasing success of liver transplantation has provoked research into the utilization of animal organs for clinical transplantation. The technique of whole-organ decellularization aims at the removal of the antigenic cellular content, thus evading the immune rejection cascade and the production of complex three-dimensional extracellular matrices of the entire organs with preservation of their intrinsic vascular networks rendering them transplantable. The aim of this study was the production of decellularized rabbit liver matrices by applying a simple, rapid perfusion decellularization technique and their characterization (both qualitatively and quantitatively). MATERIALS AND METHODS: Decellularization of the caudate hepatic lobes of New Zealand white rabbits (n = 22) was achieved through sequential perfusion of the portal venous system with deionized water, 0.8% Triton X-100 and 0.8% sodium dodecyl sulphate (SDS). Decellularized specimens were characterized both qualitatively (histology, fluoroscopy, corrosion casting and scanning electron microscopy) and quantitatively (total collagen assay [colorimetric] and total DNA assay [Hoechst 33258]). A Student's t-test was used to compare quantitative laboratory results before and after decellularization. A probability (P) value of <0.05 was considered significant. RESULTS: Effective decellularization was achieved as proven by histology and quantitative assessment (DNA remnants <1.5%, P = 0.0009), while preserving 68% of the total collagen content (P = 0.003). Portal vascular network integrity was confirmed by fluoroscopy and corrosion casting. Scanning electron microscopy also confirmed the preservation of the three-dimensional architecture. CONCLUSIONS: Liver perfusion decellularization technique using both 0.8% Triton X-100 and 0.8% SDS is a simple and rapid technique, yielding efficiently decellularized liver matrices preserving their vascular integrity, 3D architecture and 68% of total collagen content. PMID- 26669726 TI - Xenotransplantation literature update, September-October 2015. PMID- 26669727 TI - Corrigendum. PMID- 26669728 TI - Effects of an empowerment program for self-management among rural older adults with hypertension in South Korea. AB - OBJECTIVE: This study aimed to examine the effects of an empowerment program for hypertension self-management among rural older adults in South Korea. DESIGN: A pretest-posttest controlled design for a 12-month hypertension self-management program with assessments at commencement, 6 months and 12 months. SETTING: Two subsistence farming areas. PARTICIPANTS: Subsistence farmers aged 65 and over: intervention group (n = 41) and control group (n = 36). INTERVENTION: Twelve month empowerment program for hypertension self-management. MAIN OUTCOME MEASURES: Self-efficacy, social support, self-care behaviours, blood pressure control and renal function. RESULTS: There were significant interactions of group by time for self-efficacy (P < 0.001) and self-care behaviour (P = 0.019). Blood pressure control at 12 months also showed a significant improvement in the empowered group compared with the control group (82.8% versus 56.8%, P < 0.014). Other clinical outcomes, including systolic blood pressure (P = 0.006) and renal function (P < 0.001), showed significant interactions of group by time. CONCLUSIONS: The empowerment program was effective for rural older adults with hypertension in South Korea. Further investigation of the relationships among core components of empowerment would be beneficial. PMID- 26669729 TI - Systematic review with meta-analysis: 10- or 14-day sequential therapy vs. 14-day triple therapy in the first line treatment of Helicobacter pylori infection. AB - BACKGROUND: Whether 10-day or 14-day sequential therapy is superior to 14-day triple therapy in the first-line treatment of Helicobacter pylori remains controversial. AIM: To compare the efficacy of 10-day or 14-day sequential therapy vs. 14-day triple therapy. METHODS: Randomised controlled trials (RCTs) comparing 10-day or 14-day sequential therapy and 14-day triple therapy as first line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and adverse effects, respectively. RESULTS: Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14-day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14-day triple therapy [Risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99-1.08, P = 0.145]. However, there was significant heterogeneity (I(2) = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14-day sequential therapy was significantly more effective than 14 day triple therapy (RR: 1.09, 95% CI: 1.04-1.16, P = 0.002), and there was no significant heterogeneity (I(2) = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14-day triple therapy (RR: 1.03, 95% CI: 0.98-1.09, P = 0.207). There was no significant difference in the risk of adverse effects. CONCLUSION: Sequential therapy given for 14 days, but not 10 days, was more effective than 14-day triple therapy as first-line treatment. PMID- 26669730 TI - Isotonic saline in elderly men: an open-labelled controlled infusion study of electrolyte balance, urine flow and kidney function. AB - Isotonic saline is a widely-used infusion fluid, although the associated chloride load may cause metabolic acidosis and impair kidney function in young, healthy volunteers. We wished to examine whether these effects also occurred in the elderly, and conducted a crossover study in 13 men with a mean age of 73 years (range 66-84), who each received intravenous infusions of 1.5 l of Ringer's acetate and of isotonic saline. Isotonic saline induced mild changes in plasma sodium (mean +1.5 mmol.l(-1) ), plasma chloride (+3 mmol.l(-1) ) and standard bicarbonate (-2 mmol.l(-1) ). Three hours after starting the infusions, 68% of the Ringer's acetate and 30% of the infused saline had been excreted (p < 0.01). The glomerular filtration rate increased in response to both fluids, but more after the Ringer's acetate (p < 0.03). Pre-infusion fluid retention, as evidenced by high urinary osmolality (> 700 mOsmol.kg(-1) ) and/or creatinine (> 7 mmol.l( 1) ), was a strong factor governing the responses to both fluid loads. PMID- 26669731 TI - Grand and Semigrand Canonical Basin-Hopping. AB - We introduce grand and semigrand canonical global optimization approaches using basin-hopping with an acceptance criterion based on the local contribution of each potential energy minimum to the (semi)grand potential. The method is tested using local harmonic vibrational densities of states for atomic clusters as a function of temperature and chemical potential. The predicted global minima switch from dissociated states to clusters for larger values of the chemical potential and lower temperatures, in agreement with the predictions of a model fitted to heat capacity data for selected clusters. Semigrand canonical optimization allows us to identify particularly stable compositions in multicomponent nanoalloys as a function of increasing temperature, whereas the grand canonical potential can produce a useful survey of favorable structures as a byproduct of the global optimization search. PMID- 26669732 TI - Significant Improvement of Semiconducting Performance of the Diketopyrrolopyrrole Quaterthiophene Conjugated Polymer through Side-Chain Engineering via Hydrogen Bonding. AB - Three diketopyrrolopyrrole (DPP)-quaterthiophene conjugated polymers, pDPP4T-1, pDPP4T-2, and pDPP4T-3, in which the molar ratios of the urea-containing alkyl chains vs branching alkyl chains are 1:30, 1:20, and 1:10, respectively, were prepared and investigated. In comparison with pDPP4T without urea groups in the alkyl side chains and pDPP4T-A, pDPP4T-B, and pDPP4T-C containing both linear and branched alkyl chains, thin films of pDPP4T-1, pDPP4T-2, and pDPP4T-3 exhibit higher hole mobilities; thin-film mobility increases in the order pDPP4T-1 < pDPP4T-2 < pDPP4T-3, and hole mobility of a thin film of pDPP4T-3 can reach 13.1 cm(2) V(-1) s(-1) after thermal annealing at just 100 degrees C. The incorporation of urea groups in the alkyl side chains also has an interesting effect on the photovoltaic performances of DPP-quaterthiophene conjugated polymers after blending with PC71BM. Blended thin films of pDPP4T-1:PC71BM, pDPP4T-2:PC71BM, and pDPP4T-3:PC71BM exhibit higher power conversion efficiencies (PCEs) than pDPP4T:PC71BM, pDPP4T-A:PC71BM, pDPP4T-B:PC71BM, and pDPP4T-C:PC71BM. The PCE of pDPP4T-1:PC71BM reaches 6.8%. Thin films of pDPP4T-1, pDPP4T-2, and pDPP4T-3 and corresponding thin films with PC71BM were characterized with AFM, GIXRD, and STEM. The results reveal that the lamellar packing order of the alkyl chains is obviously enhanced for thin films of pDPP4T-1, pDPP4T-2, and pDPP4T-3; after thermal annealing, slight inter-chain pi-pi stacking emerges for pDPP4T-2 and pDPP4T-3. Blends of pDPP4T-1, pDPP4T-2, and pDPP4T-3 with PC71BM show a more pronounced micro-phase separation. These observations suggest that the presence of urea groups may further facilitate the assemblies of these conjugated polymers into nanofibers and ordered aggregation of PC71BM. PMID- 26669733 TI - De-demonizing the VRAEM: A Peruvian-Cocalero Area. AB - BACKGROUND: The valley of the rivers Apurimac, Ene, and Mantaro (VRAEM) is the main center of coca production in Peru. This is a jungle area located between southern highland regions, and is notorious for the presence of drug-trafficking and the last remnants of Shining Path guerrillas. As a result, it occupies a central place in security policies in Peru, and has been "demonized" in the national imaginary. OBJECTIVE: This article explores the current situation, recent history, and most important collectives of the VRAEM, challenging stereotypes about it. METHODS: The article is based on short-term fieldwork undertaken in the VRAEM in March 2008, and long-term research conducted in Ayacucho in 2008-2009; and it is contextualized in relation to the literature on coca producing areas and drug policies. RESULTS: The negative image of the VRAEM started in the context of the 1980s-1990s coca boom and Peruvian armed conflict. State policies in the area since then have been mainly based on militarization and repression, contributing to maintain that negative image, which differs of a complex and nuanced local reality. A coca eradication campaign started in 2014, bringing major changes. CONCLUSIONS: The negative image of the VRAEM is largely unfair, and has been mainly based on stereotypes and prejudices. This negative stereotyping contributes to justify and maintain inefficient and pernicious state policies in the area, and to criminalize local people. There is an urgent need for fieldwork-based studies in the area to counteract those negative stereotypes and monitor current events. PMID- 26669735 TI - How advances in light technology have shaped ENT. AB - The development of light technologies, allowing anatomical visualisation of otherwise hidden structures, led to significant advances in ENT in the nineteenth and twentieth centuries. Natural light from the sun, and from candles, was initially harnessed using mirrors. Later, the invention of limelight and electricity preceded the emergence of the modern-day endoscope, which, in tandem with the discovery of coherent fibre-optics in the 1950s, significantly expanded the surgical repertoire available to otolaryngologists. This study aimed to trace the rich history of ENT through the specialty's use of light. PMID- 26669734 TI - Ageism and caring attitudes among nurses in oncology. AB - BACKGROUND: Although the incidence of cancer increases with age, elderly patients are often excluded from clinical trials. In addition, elderly patients are frequently undertreated in comparison to younger patients. One explanation for these observations is age stigma (i.e. ageism). In this context, this study has two objectives: (1) to replicate the results of previous studies that reported differential support of medical treatment depending on the patient's age in a different healthcare provider population (nurses rather than physicians); and (2) to determine whether support for expensive immunotherapy, adjuvant chemotherapy, or breast reconstruction is linked to ageism among nurses. METHOD: The participants were 76 nurses who specialized in oncology. They received four clinical vignettes: one vignette about an immunotherapy with a high societal cost (age of patient: 40 vs. 70 years), and three vignettes about adjuvant chemotherapy and breast reconstruction (age of patient: 35, 55, or 75 years - age was the only difference). A questionnaire and a fluency task were used to assess the participants' vision of aging. RESULTS: Our analyses show that support for immunotherapy, breast reconstruction, and chemotherapy is lower for older patients than for younger patients. Moreover, nurses' vision of aging influences support for breast reconstruction: nurses with a negative view of age discriminated more between a 75-year-old patient and a 35-year-old patient (less encouragement for the older patient). CONCLUSION: These results highlight the need for nurses and other healthcare providers to receive specific training about ageism and its consequences. PMID- 26669737 TI - Time to Death and Associated Factors among Tuberculosis Patients in Dangila Woreda, Northwest Ethiopia. AB - BACKGROUND: Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide. More than 70% of the deaths of TB patients occur during the first two months of TB treatment. The major risk factors that increase early death of TB patients are being positive for human immunodeficiency virus (HIV), being of old age, being underweight or undergoing re-treatment. OBJECTIVE: To assess the time of reported deaths and associated factors in a cohort of patients with TB during TB treatment. METHODS: An institution-based retrospective cohort study was analyzed in Dangila Woreda, Northwest Ethiopia from March 1st through March 30, 2014. All TB patients registered in the direct observed treatment (DOTs) clinic from 2008-2012 were included in the study. Data were entered into EpiData and exported to SPSS for analysis. The survival probability was analyzed by the Kaplan Meier method and Cox regression analysis was applied to investigate factors associated with death during TB treatment. RESULTS: From a total of 872 cases registered in TB registry log book, 810 were used for the analysis of which 60 (7.4%) died during the treatment. The overall mortality rate was 12.8/1000 person months of observation. A majority of TB deaths 34 (56.7%) occurred during the intensive phase of the treatment, and the median time of death was at two months of the treatment. Age, HIV status and baseline body weight were independent predictors of death during TB treatment. CONCLUSIONS: Most deaths occurred in the first two months of TB treatment. Old age, TB/HIV co-infection and a baseline body weight of <35 kg increased the mortality during TB treatment. Therefore, a special follow up of TB patients during the intensive phase, of older patients and of TB/HIV co-infected cases, as well as nutritionally supplementing for underweight patients may be important to consider as interventions to reduce deaths during TB treatment. PMID- 26669738 TI - The Price of a Neglected Zoonosis: Case-Control Study to Estimate Healthcare Utilization Costs of Human Brucellosis. AB - Human brucellosis has reemerged as a serious public health threat to the Bedouin population of southern Israel in recent years. Little is known about its economic implications derived from elevated healthcare utilization (HCU). Our objective was to estimate the HCU costs associated with human brucellosis from the insurer perspective. A case-control retrospective study was conducted among Clalit Health Services (CHS) enrollees. Brucellosis cases were defined as individuals that were diagnosed with brucellosis at the Clinical Microbiology Laboratory of Soroka University Medical Center in the 2010-2012 period (n = 470). Control subjects were randomly selected and matched 1:3 by age, sex, clinic, and primary physician (n = 1,410). HCU data, demographic characteristics and comorbidities were obtained from CHS computerized database. Mean+/-SD age of the brucellosis cases was 26.6+/-17.6 years. 63% were male and 85% were Bedouins. No significant difference in Charlson comorbidity index was found between brucellosis cases and controls (0.41 vs. 0.45, respectively, P = 0.391). Before diagnosis (baseline), the average total annual HCU cost of brucellosis cases was slightly yet significantly higher than that of the control group ($439 vs. $382, P<0.05), however, no significant differences were found at baseline in the predominant components of HCU, i.e. hospitalizations, diagnostic procedures, and medications. At the year following diagnosis, the average total annual HCU costs of brucellosis cases was significantly higher than that of controls ($1,327 vs. $380, respectively, P<0.001). Most of the difference stems from 7.9 times higher hospitalization costs (p<0.001). Additional elevated costs were 3.6 times higher laboratory tests (P<0.001), 2.8 times higher emergency room visits (P<0.001), 1.8 times higher medication (P<0.001) and 1.3 times higher diagnostic procedures (P<0.001). We conclude that human brucellosis is associated with elevated HCU costs. Considering these results in cost-effective analyses may be crucial for both reducing health inequities and optimal allocation of health systems' scarce resources. PMID- 26669739 TI - Management of Pediatric Perforated Appendicitis: Comparing Outcomes Using Early Appendectomy Versus Solely Medical Management. AB - BACKGROUND: There is controversy regarding whether children with perforated appendicitis should receive early appendectomy (EA) versus medical management (MM) with antibiotics and delayed interval appendectomy. The objective of this study was to compare outcomes of children with perforated appendicitis who receive EA versus MM. METHODS: Case review of consecutive children <18 years of age with perforated appendicitis who received either EA or MM during an 8-year period. Criteria for hospital discharge included patient being afebrile for at least 24 hours, pain-free and able to tolerate oral intake. RESULTS: Of 203 patients diagnosed with perforated appendicitis, 122 received EA and 81 received MM. All received parenteral antibiotic therapy initiated in the emergency department and continued during hospitalization. There were no significant differences between groups in mean patient age, mean complete blood count total white blood cells count, gender distribution, rates of emergency department fever or rates of intra-abdominal infection (abscess or phlegmon) identified on admission. Compared with patients receiving MM, those receiving EA experienced significantly fewer (1) days of hospitalization, parenteral antibiotic therapy and in-hospital fever; (2) radiographic studies, percutaneous drainage procedures and placement of central venous catheters performed; (3) post admission intra abdominal complications and (4) unscheduled repeat hospitalizations after hospital discharge. Only 1 EA-managed patient developed a postoperative wound infection. CONCLUSIONS: Children with perforated appendicitis who receive EA experience significantly less morbidity and complications versus those receiving MM. The theoretical concern for enhanced morbidity associated with EA management of perforated appendicitis is not supported by our analysis. PMID- 26669740 TI - Predictors of Outcome in Pediatric Osteomyelitis: Five Years Experience in a Single Tertiary Center. AB - BACKGROUND: Acute haematogenous osteomyelitis is a bacterial infection of bone, which occurs most frequently in children. Outcomes are excellent for the majority of children, but a minority develop complicated osteomyelitis. Predicting which children will develop complicated osteomyelitis remains a challenge, particularly in developed countries where most patients are discharged home after a relatively short period in hospital. METHODS: We conducted a 5-year retrospective case note review of all children aged 3 months to 16 years admitted with a diagnosis of acute haematogenous osteomyelitis. We compared standardized clinical and laboratory parameters in those who developed simple and complicated osteomyelitis. RESULTS: Of the 299 children who met inclusion, 241 (80.6%) had simple and 58 (19.4%) had complicated osteomyelitis. The major predictors of complicated disease were older age, a temperature greater than 38.5 degrees C and a higher C-reactive protein at admission. CONCLUSIONS: A risk prediction model, utilizing information available shortly after hospitalization, allows early identification of children at greatest risk of developing complicated osteomyelitis. PMID- 26669741 TI - Immunogenicity of Influenza Vaccination in Patients With Cancer. AB - BACKGROUND: Influenza leads to significant morbidity and mortality in patients with cancer. Patients with cancer receiving chemotherapy may not mount an adequate immune response to the vaccine. We performed this pilot study to evaluate the immunogenicity of influenza vaccination in patients with cancer receiving chemotherapy. MATERIALS AND METHODS: During the 2011 to 2012 influenza season, patients undergoing chemotherapy for solid tumors were given trivalent inactivated influenza vaccine either on the day of chemotherapy (schedule A) or a week before chemotherapy (schedule B) by a single 0.5 mL injection in the deltoid muscle region. This was not a randomized trial. Hemagglutination inhibition assays were performed on blood samples from these patients taken at baseline, and 4 weeks postvaccination. Seroconversion rate (>4-fold increase in titers) and seroprotection rates (postvaccination titers of >1:40) were calculated for each vaccine component: influenza A (H1N1), A (H3N2) and B. RESULTS: A total of 18 patients received influenza vaccination as part of this pilot study. Of these, 8 patients received the vaccine on schedule A and 10 patients received the vaccine on schedule B. Geometric mean titers against each strain significantly improved after vaccination for both groups, as measured by signed rank test. Seroconversion to at least 1 strain was observed in 75% of patients on schedule A, and 70% of patients vaccinated on schedule B. Seroprotection to at least 1 strain was observed in 100% of patients in the schedule A group, and 60% of patients vaccinated on schedule B. Seroconversion and seroprotection rates against the 3 influenza strains were not significantly different between the 2 groups. CONCLUSIONS: Patients with nonhematological malignancies who are receiving chemotherapy mount an immune response to influenza vaccination. Timing of influenza vaccination in relation to chemotherapy does not seem to matter. PMID- 26669742 TI - Chronological Age and Risk of Chemotherapy Nonfeasibility: A Real-Life Cohort Study of 153 Stage II or III Colorectal Cancer Patients Given Adjuvant-modified FOLFOX6. AB - OBJECTIVES: To assess nonfeasibility of adjuvant-modified FOLFOX6 chemotherapy in patients with stage II or III colorectal cancer. METHODS: Consecutive patients managed between 2009 and 2013 in 2 teaching hospitals in the Paris urban area were included in the CORSAGE (COlorectal canceR, AGe, and chemotherapy fEasability study) cohort study. Nonfeasibility was defined by the frequencies of empirical first-cycle dose reduction (>15%), early discontinuation (<12 cycles), and low relative dose intensity (RDI) (<0.85). Risk factors for chemotherapy nonfeasibility were identified using multivariate logistic regression. RESULTS: Among 153 patients, 56.2% were male (median age, 65.6 y; 35.3%>=70 y; 7.3% with performance status [PS]>=2). For 5-fluorouracil (5-FU), 20.9% of patients had first-cycle dose reduction and 28.1% early discontinuation; RDI was 0.91 (25th to 75th percentiles, 0.68 to 0.99). Factors independently associated with first cycle 5-FU dose reduction were aged 65 to 69 years versus those younger than 65 years (adjusted odds ratio [aOR], 5.5; 95% confidence interval [CI], 1.5-19.9) but not age 70 years and older, PS>=2 (aOR, 6.02; 95% CI, 1.15-31.4), higher Charlson Comorbidity Index (aOR1-point increase, 1.4; 95% CI, 1.05-1.82), or larger number of medications (aOR 1-medication increase, 1.19; 95% CI, 1.00 1.42). Oxaliplatin dose reduction occurred in 52.3% of patients and early discontinuation in 62.7%; the latter was more common in the 70 years and older group (92.6% vs. 74.6% in the <65-y group; P=0.01); RDI was 0.7 (95% CI, 0.55 0.88). CONCLUSIONS: In the real-world setting, compared with their younger and older counterparts, patients aged 65 to 69 years given modified FOLFOX6 for stage II or III colorectal cancer had higher frequencies of 5-FU nonfeasibility defined based on first-cycle dose reduction, early discontinuation, and RDI; and these differences were independent from PS, comorbidities, and number of medications. PMID- 26669743 TI - Benefits of Deep Transcranial Magnetic Stimulation in Alzheimer Disease: Case Series. AB - BACKGROUND: Patients diagnosed with Alzheimer disease (AD) show severe cognitive deficits. Decline in memory, language, and executive function have repeatedly been reported. Although AD affects 60% to 80% of demented elderly patients, there is currently no cure and limited treatment alternatives. OBJECTIVES: The aim of the study was to evaluate the feasibility of stimulating prefrontal cortex (PFC) with deep transcranial magnetic stimulation (dTMS) to ameliorate cognitive deficits in patients suffering from AD. METHODS: Eleven patients (6 males; mean [SD] age, 76 [7] years) in moderate to severe stages of AD received dTMS over the PFC for 20 sessions. Computerized battery (Mindstreams [MS]) and neuropsychological testing (Addenbrooke Cognitive Examination [ACE]) were used to assess cognitive performance before and after treatment. RESULTS: Compared with baseline, 60% of patients performed better on the MS battery and 77% of patients performed better on the ACE testing at the end of dTMS treatment. None of the patients performed worse on both tests at the end of treatment. The DTMS effects on the group mean in ACE and MS approached significance (P = 0.065 and P = 0.086, respectively). A dTMS-induced improvement in the ACE was significant (P = 0.001) on patients in more progressed stage (n = 6). Change in ACE negatively correlated with score at baseline. CONCLUSIONS: In sum, the current report of this novel technique indicates that deep stimulation might lead to preservation and even improvement of cognitive functions, at least during the time of treatment. Further examinations should report of long-term effects of this technique. PMID- 26669744 TI - Regarding "500-mA ECT-A Proof of Concept Report" by Prashanth Mayur, Anthony Harris, and Bangalore Gangadhar, published as Letter to the Editor in the Journal of ECT: June 2015-Volume 31-Issue 2-p e23-e26. PMID- 26669745 TI - Additional Procedures Performed During Electroconvulsive Therapy Anesthesia. PMID- 26669746 TI - Synthesis of a far-red fluorophore and its use as an esterase probe in living cells. AB - We report the synthesis of a new far-red fluorophore, 1,3-dichloro-7-hydroxy-2H spiro[acridine-9,1'-cyclohexane]-2',5'-diene-2,4'-dione (DSACO), which was modified to make two esterase probes: DSACO-2-AME and DSACO-7-AME. Both probes act as "turn-on" substrates for esterases and lipases. DSACO-2-AME exhibited efficient esterase-activated fluorescence inside living cells and is a stable, far-red alternative for the widely-used fluorescein diacetate. PMID- 26669747 TI - Editorial: Medication-related osteonecrosis of the jaw (MRONJ): Bisphosphonates, antiresorptives, and antiangiogenic agents. What next? PMID- 26669748 TI - Cone beam computed tomography (CBCT) for diagnosis and treatment planning in periodontology: A systematic review. AB - OBJECTIVE: The improvement in diagnostic accuracy and optimization of treatment planning in periodontology through the use of three-dimensional imaging with cone beam computed tomography (CBCT) is discussed controversially in the literature. The objective was to identify the best available external evidence for the indications of CBCT for periodontal diagnosis and treatment planning in specific clinical situations. DATA SOURCES: A systematic literature search was performed for articles published by 2 March 2015 using electronic databases and hand search. Two reviewers performed the study selection, data collection, and validity assessment. PICO and PRISMA criteria were applied. From the combined search, seven studies were finally included. CONCLUSION: The case series were published from the years 2009 to 2014. Five of the included publications refer to maxillary and/or mandibular molars and two to aspects related to vertical bony defects. Two studies show a high accuracy of CBCT in detecting intrabony defect morphology when compared to periapical radiographs. Particularly, in maxillary molars, CBCT provides high accuracy for detecting furcation involvement and morphology of surrounding periodontal tissues. CBCT has demonstrated advantages, when more invasive treatment approaches were considered in terms of decision making and cost benefit. Within their limits, the available data suggest that CBCT may improve diagnostic accuracy and optimize treatment planning in periodontal defects, particularly in maxillary molars with furcation involvement, and that the higher irradiation doses and cost-benefit ratio should be carefully analyzed before using CBCT for periodontal diagnosis and treatment planning. PMID- 26669749 TI - Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture. AB - Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays. PMID- 26669750 TI - New phenazine analogues from Streptomyces sp. IFM 11694 with TRAIL resistance overcoming activities. AB - Two new phenazine derivatives, aotaphenazine (1) and 5,10-dihydrophencomycin (2), were isolated from the ethyl acetate extract of Streptomyces sp. IFM 11694. In addition, the known 1-phenazinecarboxylic acid (3), phencomycin (4) and 1,6 phenazinedicarboxylic acid (5) were identified. The structures of the isolated compounds (1-5) were characterized by spectroscopic methods including NMR and mass spectrometry data. Compound 1 showed the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance at concentration of 12.5 MUM. Aotaphenazine (1) enhanced the levels of apoptosis inducing proteins DR4, DR5, p53 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant human gastric adenocarcinoma (AGS) cells in a dose-dependent manner. PMID- 26669751 TI - Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 2. Synthesis of 7(S)-7-deoxy-7-(4-morpholinocarbonylphenylthio)lincomycin and its 3-dimensional analysis with rRNA. AB - Lincomycin derivatives, which possess a hetero ring at the C-7 position via sulfur atom, were synthesized by three types of reactions: (1) Mitsunobu reaction of 2,3,4-tris-O-(trimethylsiliyl)lincomycin (1) with the corresponding thiol, (2) SN2 reaction of 7-O-methanesulfonyl-2,3,4-tris-O-(trimethylsiliyl)lincomycin (2) with the corresponding thiol and (3) Pd-catalyzed cross-coupling reaction of 7 deoxy-7-epi-7-mercaptolincomycin (35) with the corresponding aryl halides. As a result, compound 28 had potent antibacterial activities against major pathogens, which caused respiratory infections, even compared with clindamycin. On the other hand, compound 38 showed most potent activities against a variety of Streptococcus pneumoniae with erm gene. PMID- 26669752 TI - Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii. AB - Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l( 1)) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l(-1) with a clinically achievable concentration of polymyxin B (2 mg l(-1)) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ?4 mg l(-1)). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'. PMID- 26669753 TI - Cell wall-affecting antibiotics modulate natural transformation in SigH expressing Staphylococcus aureus. PMID- 26669754 TI - Amethysione and amethysamide, new metabolites from Streptosporangium amethystogenes BCC 27081. PMID- 26669755 TI - Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 1. Newly generated antibacterial activities against Gram-positive bacteria with erm gene by C-7 modification. AB - We synthesized 7(S)-7-deoxy-7-arylthiolincomycin derivatives possessing a heterocyclic ring at the C-7 position via sulfur atom by either Mitsunobu reaction of 2,3,4-tris-O-(trimethylsiliyl)lincomycin or SN2 reaction of 7-O methanesulfonyl-2,3,4-tri-O-trimethylsiliyllincomycin. As a result, 7(S)-7-deoxy 7-arylthiolincomycin derivatives 16, 21 and 27 exhibited antibacterial activities against respiratory infection-related Gram-positive bacteria with erm gene, although clindamycin did not have any activities against those pathogens. Furthermore, 7(S)-configuration of lincomycin derivatives was found to be necessary for enhancing antibacterial activities from the comparison results of configurations of 16 (S-configuration) and 30 (R-configuration) at the 7 position. PMID- 26669756 TI - MCO Membranes: Enhanced Selectivity in High-Flux Class. AB - Novel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure, and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin. PMID- 26669757 TI - Substantial Impact of School Closure on the Transmission Dynamics during the Pandemic Flu H1N1-2009 in Oita, Japan. AB - BACKGROUND: School closure is considered as an effective measure to prevent pandemic influenza. Although Japan has implemented many class, grade, and whole school closures during the early stage of the pandemic 2009, the effectiveness of such a school closure has not been analysed appropriately. In addition, analysis based on evidence or data from a large population has yet to be performed. We evaluated the preventive effect of school closure against the pandemic (H1N1) 2009 and examined efficient strategies of reactive school closure. MATERIALS AND METHODS: Data included daily reports of reactive school closures and the number of infected students in the pandemic in Oita City, Japan. We used a regression model that incorporated a time delay to analyse the daily data of school closure based on a time continuous susceptible-exposed-infected-removed model of infectious disease spread. The delay was due to the time-lag from transmission to case reporting. We simulated the number of students infected daily with and without school closure and evaluated the effectiveness. RESULTS: The model with a 3-day delay from transmission to reporting yielded the best fit using R2 (the coefficient of determination). This result suggests that the recommended period of school closure is more than 4 days. Moreover, the effect of school closure in the simulation of school closure showed the following: the number of infected students decreased by about 24% at its peak, and the number of cumulative infected students decreased by about 8.0%. CONCLUSIONS: School closure was an effective intervention for mitigating the spread of influenza and should be implemented for more than 4 days. School closure has a remarkable impact on decreasing the number of infected students at the peak, but it does not substantially decrease the total number of infected students. PMID- 26669758 TI - Remote coral reefs can sustain high growth potential and may match future sea level trends. AB - Climate-induced disturbances are contributing to rapid, global-scale changes in coral reef ecology. As a consequence, reef carbonate budgets are declining, threatening reef growth potential and thus capacity to track rising sea-levels. Whether disturbed reefs can recover their growth potential and how rapidly, are thus critical research questions. Here we address these questions by measuring the carbonate budgets of 28 reefs across the Chagos Archipelago (Indian Ocean) which, while geographically remote and largely isolated from compounding human impacts, experienced severe (>90%) coral mortality during the 1998 warming event. Coral communities on most reefs recovered rapidly and we show that carbonate budgets in 2015 average +3.7 G (G = kg CaCO3 m(-2) yr(-1)). Most significantly the production rates on Acropora-dominated reefs, the corals most severely impacted in 1998, averaged +8.4 G by 2015, comparable with estimates under pre human (Holocene) disturbance conditions. These positive budgets are reflected in high reef growth rates (4.2 mm yr(-1)) on Acropora-dominated reefs, demonstrating that carbonate budgets on these remote reefs have recovered rapidly from major climate-driven disturbances. Critically, these reefs retain the capacity to grow at rates exceeding measured regional mid-late Holocene and 20th century sea-level rise, and close to IPCC sea-level rise projections through to 2100. PMID- 26669759 TI - At the cross-roads of participatory research and biomarker discovery in autism: the need for empirical data. AB - BACKGROUND: Identifying biomarkers for autism can improve outcomes for those affected by autism. Engaging the diverse stakeholders in the research process using community-based participatory research (CBPR) can accelerate biomarker discovery into clinical applications. However, there are limited examples of stakeholder involvement in autism research, possibly due to conceptual and practical concerns. We evaluate the applicability of CBPR principles to biomarker discovery in autism and critically review empirical studies adopting these principles. METHODS: Using a scoping review methodology, we identified and evaluated seven studies using CBPR principles in biomarker discovery. RESULTS AND CONCLUSIONS: The limited number of studies in biomarker discovery adopting CBPR principles coupled with their methodological limitations suggests that such applications are feasible but challenging. These studies illustrate three CBPR themes: community assessment, setting global priorities, and collaboration in research design. We propose that further research using participatory principles would be useful in accelerating the pace of discovery and the development of clinically meaningful biomarkers. For this goal to be successful we advocate for increased attention to previously identified conceptual and methodological challenges to participatory approaches in health research, including improving scientific rigor and developing long-term partnerships among stakeholders. PMID- 26669760 TI - Is tracheostomy a better choice than translaryngeal intubation for critically ill patients requiring mechanical ventilation for more than 14 days? A comparison of short-term outcomes. AB - BACKGROUND: Tracheostomy is recommended for patients receiving mechanical ventilation (MV) for 14 days or more in the intensive care unit (ICU). Nevertheless, many patients undergoing prolonged MV remain intubated via the translaryngeal route. The aim of this study was to examine the influence of tracheostomy and persistent translaryngeal intubation on short-term outcomes in patients mechanically ventilated for >=14 days. METHODS: A retrospective study was conducted using the admissions database of a 75-bed ICU from January 1, 2012, to December 31, 2012. Patients who required prolonged MV without tracheostomy at the time of initiation of a ventilator were included. The outcomes were successful weaning, and ICU and in-hospital death. Cox models were constructed to calculate the influence of tracheostomy on the outcome measures while adjusting for other potentially confounding factors. RESULTS: Of the 508 patients requiring prolonged MV, 164 were tracheostomized after a median 18 days of MV. Patients in whom translaryngeal intubation was maintained had significantly higher ICU (42.7% versus 17.1%, p <0.001) and in-hospital (54.1% versus 22.0%, p <0.001) mortality rates, and a significantly lower successful weaning rate (40.4% versus 68.9%, p <0.001). The results were consistent after matching for the propensity score of performing tracheostomy. Furthermore, a time-dependent covariate Cox model showed that a tracheostomy was independently associated with lower in-hospital mortality (adjusted hazard ratio [aHR], 0.26; 95% confidence interval [CI], 0.18-0.39) and higher successful weaning rate (aHR, 2.05; 95% CI, 1.56-2.68). CONCLUSIONS: Tracheostomy is associated with lower in-hospital mortality and higher successful weaning rates in ICU patients receiving prolonged MV. However, the cost effectiveness and long-term outcomes of tracheostomy for this cohort require further study. PMID- 26669763 TI - IBD: IBD and spondyloarthritis: joint management. PMID- 26669761 TI - Effectiveness of Chinese herbal medicine for cancer palliative care: overview of systematic reviews with meta-analyses. AB - Chinese herbal medicines (CHM) are often used in managing cancer related symptoms but their effectiveness and safety is controversial. We conducted this overview of meta-analyses to summarize evidence on CHM for cancer palliative care. We included systematic reviews (SRs) with meta-analyses of CHM clinical trials on patients diagnosed with any type of cancer. Methodological quality of included meta-analyses was assessed with the Methodological Quality of Systematic Reviews (AMSTAR) Instrument. Fifty-one SRs with meta-analyses were included. They covered patients with lung (20 SRs), gastric (8 SRs), colorectal (6 SRs), liver (6 SRs), breast (2 SRs), cervical (1 SR), esophageal (1 SR), and nasopharyngeal (1 SR) cancers. Six SRs summarized evidence on various types of cancer. Methodological quality of included meta-analyses was not satisfactory. Overall, favorable therapeutic effects in improving quality of life among cancer patients have been reported. Conflicting evidence exists for the effectiveness of CHM in prolonging survival and in reducing chemotherapy and/or radiotherapy related toxicities. No serious adverse effects were reported in all included studies. Evidence indicated that CHM could be considered as an option for improving quality of life among patients receiving palliative care. It is unclear if CHM may increase survival, or reduce therapy related toxicities. PMID- 26669764 TI - Liver cancer: TGF-beta and cholangiocarcinoma. PMID- 26669765 TI - Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis. AB - BACKGROUND: Evidence is accumulating that a preclinical phase is present before the onset of clinical signs and symptoms of rheumatoid arthritis (RA). This phase represents an important therapeutic window within which interventions can dramatically modulate outcomes. An agent able to prevent RA for high risk individuals in this phase is therefore desired. In this study, we investigated whether tryptophan metabolite, 5-hydroxytryptophan (5-HTP) or 5-methoxytryptophan (5-MTP), can act as such an agent for primary prevention of collagen-induced arthritis (CIA). METHODS: Mouse splenocytes were pretreated with 5-HTP or 5-MTP and activated by anti-CD3 plus anti-CD28 antibodies in vitro. The percentages of interferon-gamma (IFNgamma)(+)CD4(+) T cells and interleukin-17 (IL-17)(+)CD4(+) T cells were measured by flow cytometry. The production of pro-inflammatory cytokines, serotonin and kynurenine was measured by enzyme-linked immunosorbent assay. A CIA model was used to investigate the in vivo effects of 5-HTP on the prevention of arthritis. RESULTS: 5-HTP decreased the percentages of IFNgamma(+)CD4(+) T cells and IL-17(+)CD4(+) T cells and suppressed the production of IL-2, IL-4, IL-6, IL-17, tumor necrosis factor-alpha (TNFalpha) and IFNgamma in activated splenocytes. 5-HTP administered before induction decreased the disease activities in CIA mice and suppressed the production of TNFalpha, IL 6 and cyclooxygenase-2 in arthritic joints. 5-HTP also increased serotonin, but decreased kynurenine in the CIA mice. CONCLUSIONS: 5-HTP suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators. 5 HTP supplement before induction ameliorates arthritis in a CIA model. PMID- 26669767 TI - The Spread of CTX-M-Type Extended-Spectrum beta-Lactamases in Brazil: A Systematic Review. AB - The aim of this study was evaluate the spread of CTX-M-type extended-spectrum beta-lactamase variants in microorganisms involved in both hospital- and community-acquired infections in different regions of Brazil to determine their epidemiology and identify areas for further research. Thirty-six studies were included and analyzed. Most of the studies were conducted in the southeastern (66.7%, 24/36), southern (22.2%, 8/36), and northeastern (8.3%, 3/36) regions of Brazil. No study was conducted in the northern or midwestern region. CTX-M producing bacteria were isolated exclusively from humans in both hospital and community environments. The microorganisms that were most commonly associated with the presence of the blaCTX-M gene were Klebsiella pneumoniae and Escherichia coli. The beta-lactamases of the CTX-M family that were most frequently identified in Brazil were CTX-M-2 and CTX-M-15, especially in the southeast where these variants are often detected. In this systematic review, the microorganisms that were most commonly associated with the presence of the blaCTX-M gene were K. pneumoniae and E. coli. CTX-M-2 and CTX-M-15 were the most dominant variants of the CTX-M family, followed by CTX-M-8, CTX-M-9, and CTX-M-59. A higher frequency of CTX-M variants was found in the southeastern region, especially in the states of Sao Paulo and Rio de Janeiro, where CTX-M-2 and CTX-M-15 are predominant. PMID- 26669766 TI - A multicentre randomized controlled trial of gentle assisted pushing in the upright posture (GAP) or upright posture alone compared with routine practice to reduce prolonged second stage of labour (the Gentle Assisted Pushing study): study protocol. AB - BACKGROUND: Fundal pressure (pushing on the upper part of the uterus in the direction of the birth canal) is often performed in routine practice, however the benefit and indications for its use are unclear and vigorous pressure is potentially harmful. There is some evidence that it may be applied routinely or to expedite delivery in some situations (e.g. fetal distress or maternal exhaustion), particularly in settings where other methods of achieving delivery (forceps, vacuum) are not available. Gentle assisted pushing (GAP) is an innovative method of applying gentle but steady pressure to the uterine fundus with the woman in an upright posture. This trial aims to evaluate the use of GAP in an upright posture, or upright posture alone, on reducing the mean time of delivery and the associated maternal and neonatal complications in women not having delivered following 15-30 min in the second stage of labour. METHODS/DESIGN: We will conduct a multicentre, randomized, unblinded, controlled trial with three parallel arms (1:1:1). 1,145 women will be randomized at three hospitals in South Africa. Women will be eligible for inclusion if they are >=18 years old, nulliparous, gestational age >= 35 weeks, have a singleton pregnancy in cephalic presentation and vaginal delivery anticipated. Women with chronic medical conditions or obstetric complications are not eligible. If eligible women are undelivered following 15-30 min in the second stage of labour, they will be randomly assigned to: 1) GAP in the upright posture, 2) upright posture only and 3) routine practice (recumbent/supine posture). The primary outcome is the mean time from randomization to complete delivery. Secondary outcomes include operative delivery, adverse neonatal outcomes, maternal adverse events and discomfort. DISCUSSION: This trial will establish whether upright posture and/or a controlled method of applying fundal pressure (GAP) can improve labour outcomes for women and their babies. If fundal pressure is found to have a measurable beneficial effect, this gentle approach can be promoted as a replacement for the uncontrolled methods currently in use. If it is not found to be useful, fundal pressure can be discouraged. PMID- 26669768 TI - Surgical Outcomes after Pulmonary Resection for Non-Small Cell Lung Cancer with Localized Pleural Seeding First Detected during Surgery. AB - OBJECTIVES: Curative resection is not indicated for non-small cell lung cancer (NSCLC) with pleural seeding, which is classified as stage IV (M1a) disease. However, some patients with a presumably resectable main tumor are diagnosed with localized pleural seeding during surgery. METHODS: A retrospective analysis was performed of 3,975 patients who underwent surgery for NSCLC from 2000 to 2011. Among these cases, 78 (2.0%) patients had unexpected pleural seeding detected during surgery. Exploration with pleural biopsy was performed in 42 of these patients (exploration-only group) and pulmonary resection, including for the main tumor, was performed in 36 cases (resection group; sublobar resection in 12, lobectomy in 21, and pneumonectomy in 3 patients). Survival and cancer progression rates were estimated using the Kaplan-Meier method. Cox proportional hazard regression was used to evaluate prognostic factors associated with survival. RESULTS: Adenocarcinoma was the predominant histological type in both the exploration and resection groups (88.1 and 86.1%, respectively). Epidermal growth factor receptor expression was detected in 22 (52.4%) patients of the exploration group and 21 (58.3%) patients of the resection group. Baseline characteristics including age, sex, comorbidity, pulmonary function, and clinical T/N status were not significantly different between the two groups. There were no postoperative deaths in either group but postoperative complications occurred in two (4.8%) patients of the exploration group and three (8.3%) patients of the resection group. The overall 3- and 5-year survival rates in the exploration group were 41.1 and 15.2%, respectively, with a median survival time (MST) of 33 months, whereas they were 66.7 and 42.7%, respectively, in the resection group, with a 52-month MST (p = 0.012). Local and regional progression-free rates were significantly different (p < 0.001 and p = 0.029, respectively) between groups, whereas no difference was seen in the distant metastasis rates (p = 0.957). In multivariate survival analysis, surgical resection was the only significant prognostic factor (p = 0.01). CONCLUSIONS: Pulmonary resection including the main tumor, regardless of resection extent, may increase long-term survival for NSCLC patients with localized pleural seeding first detected during surgery, without a significant increase in hospital mortality or morbidity. PMID- 26669769 TI - Lung Cancer with Unexpected Localized Pleural Dissemination Detected during Surgery: Should We Stop Surgery or Should We Go On? PMID- 26669770 TI - Double Bipolar Sealing of the Pulmonary Artery Improves the Bursting Pressures. AB - Background In every anatomic lung resection, branches of the pulmonary artery have to be divided. In open surgery, this can be done with ligatures or staplers. In endoscopic surgery, only an endostapler can be used. By routing we ligate the vessels double. Bipolar sealing had yielded promising results, so we wanted to know if we can improve the bursting pressures especially in case of larger vessels by double sealing. Methods Experiments were performed on preparations of the left pulmonary artery extracted at the slaughterhouse. A pressure sensor was implanted at the central end to provide digital measurement of the pneumatic load on the vessel seal and thus establish bursting pressure in each case. Vessels were sealed with MARSEAL 5 (Gebruder Martin GmbH & Co KG, Tuttlingen, Germany) and SealSafe G3 electric current. The vessels investigated were separated into three sizes: 1 to 6 mm, 7 to 12 mm, and >12 mm. The groups (n = 12 in each) were investigated for each vessel size-Group 1: ligature; Group 2: single seal; Group 3: double seals separated by gap of 0.5 cm; and Group 4: double seals separated by gap of 1.0 cm. Mean bursting pressure (mbar) was calculated for each group. Differences between groups were calculated with Mann-Whitney U test; differences with p < 0.05 were considered significant. Results The ligated vessels in the 1 to 6 mm group showed the highest bursting pressures (mean 515.7 +/- 39.6 mbar). Mean bursting pressure in the single seal group was 231.6 +/- 47.5 mbar. This was not significantly different from the group with double seals placed 0.5 cm apart. However, bursting pressures were significantly higher in the group with double seals placed 1 cm apart (p < 0.001). Mean value in this case was 308.5 +/- 44.5 mbar. In the 7 to 12 mm vessels, mean bursting pressure was highest with ligation at 361 +/- 67.1 mbar but was significantly higher in both groups with double bipolar seals (180.3 +/- 52.1 mbar with 0.5-cm separation and 277.0 +/- 64.5 with 1-cm separation) than in the single seal group (102.7 +/- 16.1 mbar). In large vessels (>12 mm), mean bursting pressures were low (66.3 +/- 12.7 mbar) with single seals but were significantly higher with double seals (162.3 +/- 35.8 mbar [0.5-cm separation] and 137.3 +/- 22.9 mbar [1-cm separation]). Conclusions In the ex vivo model of the pulmonary artery, double seals revealed significantly higher bursting pressures than single seals. If there is enough vessel length, the two seals should be placed 1 cm apart. PMID- 26669771 TI - Social Media and Men's Health: A Content Analysis of Twitter Conversations During the 2013 Movember Campaigns in the United States, Canada, and the United Kingdom. AB - The Movember Foundation raises awareness and funds for men's health issues such as prostate and testicular cancers in conjunction with a moustache contest. The 2013 Movember campaigns in the United States, Canada, and the United Kingdom shared the same goal of creating conversations about men's health that lead to increased awareness and understanding of the health risks men face. Our objective was to explore Twitter conversations to identify whether the 2013 Movember campaigns sparked global conversations about prostate cancer, testicular cancer, and other men's health issues. We conducted a content analysis of 12,666 tweets posted during the 2013 Movember campaigns in the United States, Canada, and the United Kingdom (4,222 tweets from each country) to investigate whether tweets were health-related or non-health-related and to determine what topics dominated conversations. Few tweets ( n = 84, 0.7% of 12,666 tweets) provided content-rich or actionable health information that would lead to awareness and understanding of men's health risks. While moustache growing and grooming was the most popular topic in U.S. tweets, conversations about community engagement were most common in Canadian and U.K. tweets. Significantly more tweets co-opted the Movember campaign to market products or contests in the United States than Canada and the United Kingdom ( p < .05). Findings from this content analysis of Twitter suggest that the 2013 Movember campaigns in the United States, Canada, and the United Kingdom sparked few conversations about prostate and testicular cancers that could potentially lead to greater awareness and understanding of important men's health issues. PMID- 26669772 TI - Proposed Iraq/Afghanistan War-Lung Injury (IAW-LI) Clinical Practice Recommendations: National Academy of Sciences' Institute of Medicine Burn Pits Workshop. AB - High rates of respiratory symptoms (14%) and new-onset asthma in previously healthy soldiers (6.6%) have been reported among military personnel post deployment to Iraq and Afghanistan. The term Iraq/Afghanistan War-Lung Injury (IAW-LI) is used to describe the constellation of respiratory diseases related to hazards of war, such as exposure to burning trash in burn pits, improvised explosive devices, and sandstorms. Burnpits360.org is a nonprofit civilian website which voluntarily tracks medical symptoms among soldiers post-deployment to the Middle East. Subsequent to initiation of the Burnpits360.org website, the Department of Veterans Affairs started the Airborne Hazards and Open Burn Pit registry. This paper: (a) analyzes the latest 38 patients in the Burnpits360.org registry, validated by DD214 Forms; (b) compares strengths and weaknesses of both registries as outlined at the National Academy of Sciences Institute of Medicine Burn Pits Workshop; PMID- 26669773 TI - Developing the "Control Identity" Typology to Create More Effective Testicular Health Promotional Messaging. AB - Testicular self-examination (TSE) promotional interventions historically operate without a theoretical framework, which negatively influences their effectiveness. As TSE is critical to the early detection of testicular cancer, this behavior is an essential component to improving overall male well-being. To address this need, the Control Identity personality typology was developed to assist in creating more effective TSE promotional interventions. Four outcome control dispositions were defined a priori based on the dimensions of illusions of control and locus of control. An original 41-item survey, the Control Identity Assessment Scale, was used to assess perceived vulnerability, value of health promotion, and health outcome control among a convenience sample of 300 university males aged 18 to 35 years via a cross-sectional research design. Factor and cluster analyses were employed to extract salient factors in the data and to identify subgroups within the sample. A consistent five-factor structure matrix (~70% explained variance) served as the foundation from which a k-means cluster analysis was employed to classify four types of individuals. Significant differences were detected between clusters on primary variables, including behavioral intentions to conduct TSE. The Control Identity typology aims to provide the needed mechanism for health practitioners to create more effective preventive health messaging to promote TSE. Future implications on employing this typology to segment audiences in order to increase overall effectiveness are offered. Application of this typology could ultimately lead to increasing TSE knowledge retention, behavioral intentions, actual performance, and adherence. PMID- 26669774 TI - Mean Platelet Volume-A Predictive Factor for the Diagnosis of Nonsymptomatic Prostatitis: Results of Univariate and Multivariate Models. AB - Mean platelet volume (MPV) has been reported to be related to inflammation. Prostate-specific antigen (PSA) is a protein produced by the prostate, and this protein may be elevated for several reasons, including prostatitis, benign prostatic hyperplasia, and/or cancer. The aim of the current study was to investigate the predictive effect of MPV values on nonsymptomatic prostatitis diagnosis and the relation between MPV and PSA. A total of 275 patients, 89 affected by benign prostate hyperplasia, 94 by prostate adenocancer, and 92 by prostatitis were included in the current study. PSA, total blood count parameters, and urine analysis were investigated. Findings were compared with the groups. The correlation between MPV and the other parameters were analyzed. Univariate and multivariate logistic regression analysis was performed to determine independent predictors of nonsymptomatic prostatitis diagnosis. MPV was significantly higher in patients with nonsymptomatic prostatitis than the other groups. There were negative correlations between MPV and age, total PSA or free PSA ( r = -.123; p = .042, r = -.235; p < .001, r = -.184; p = .006, respectively). According to multivariate regression model, only MPV was identified as the predictive factor for nonsymptomatic prostatitis (odds ratio: 1.451, 95% confidence interval [1.116, 1.887], p = .005). MPV, in the absence of other reasons that increased the MPV level, was significantly increased in cases with nonsymptomatic prostatitis; this increase is significantly higher than elevated PSA level in nonsymptomatic prostatitis patients. MPV could have a predictive value for the diagnosis of nonsymptomatic prostatitis. PMID- 26669775 TI - Healthy Eating and Active Living: Rural-Based Working Men's Perspectives. AB - There is a pressing need for health promotion programs focused on increasing healthy eating and active living among "unreached" rural-based men. The purpose of the current study was to describe rural-based working men's views about health to distil acceptable workplace approaches to promoting men's healthy lifestyles. Two focus group interviews included 21 men who worked and lived in northern British Columbia, Canada. Interviews were approximately 2 hours in duration; data were analyzed using thematic analysis. Themes inductively derived included (a) food as quick filling fuels, (b) work strength and recreational exercise, and (c) (re)working masculine health norms. Participants positioned foods as quick filling fuels both at work and home as reflecting time constraints and the need to bolster energy levels. In the theme work strength and recreational exercise, men highlighted the physical labor demands pointing to the need to be resilient in overcoming the subarctic climate and/or work fatigue in order to fit in exercise. In the context of workplace health promotion programs for men, participants advised how clear messaging and linkages between health and work performance and productivity and cultivating friendly competition among male employees were central to reworking, as well as working, with established masculine health norms. Overall, the study findings indicate that the workplace can be an important means to reaching men in rural communities and promoting healthy eating and active living. That said, the development of workplace programs should be guided by strength-based masculine virtues and values that proactively embrace work and family life. PMID- 26669776 TI - Who Do Batswana Men Prefer: Male or Female Health Providers? AB - Sexual and reproductive health (SRH) services are rarely designed specifically to meet men's needs. There is a general consensus among clinicians that males need access to SRH services. Studies have reported that men are often hesitant to go to health facilities because they feel uncomfortable being served by female providers. The study sought to determine whether men who participate in SRH services have specific preference for the gender of health workers for consultation on different types of services. A mixed-method design was employed. A combination of stratified proportional sampling of facilities and criterion purposive sampling of participants were used. Questionnaires were used to collect data from 390 participants, which were complemented with 10 in-depth interviews. Chi-square analysis with post hoc comparisons were used to determine whether there were significant differences in gender preference for specific services. Based on the data, Batswana males did not have any gender preference of the health provider for consultation on SRH services. The gender of the provider is of minor importance compared with other characteristics such as competence and confidentiality. However, the gender of the provider seems to be more important to younger men for delivery, sexually transmitted infections, voluntary counselling, and testing services. Further research is needed because the study was conducted in the city and the participants' characteristics may be unique to an urban setting. Preferences for providers among demographic groups can be useful in informing resource prioritization and help direct program efforts to reach different subgroups of males. PMID- 26669777 TI - The Health of the Nation's Custodial Grandfathers and Older Single Fathers: Findings From the Behavior Risk Factor Surveillance System. AB - Two important parent groups are solo grandfathers and single fathers raising children alone. The health of male caregivers raising children has received little attention by scholars. Investigating the health of single male caregivers raises awareness about their physical vulnerability. This study uses the 2012 Behavioral Risk Factor Surveillance System to compare health characteristics of 82 solo grandfathers with 396 single fathers aged 50 years and older. The findings suggest that grandfathers exhibited a high prevalence for various health conditions, including diabetes (44%), heart attack (27%), chronic obstructive pulmonary disease (23%), and stroke (6%). Almost half of grandfathers rated their health as fair/poor (47%), and nearly two in five had functional limitations (38%). Although older single fathers had better health characteristics than grandfathers, their health profile was poorer than population norms. Logistic regression analysis suggests that solo grandfathers are more at risk for poor health outcomes than older single fathers. Practice interventions to minimize health risks are discussed. PMID- 26669778 TI - [Erratum: Age-related alterations in brain weight]. PMID- 26669779 TI - A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease. AB - IgG4-related disease is a newly identified syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in involved organs. The incidence of IgG4-related thyroiditis in the Caucasian population of Europe is unknown. We investigated formalin-fixed thyroid gland samples of 216 patients (191 Hashimoto's thyroiditis, 5 Riedel's thyroiditis, and 20 goiters, as controls), morphologically, and immunohistochemically. Cases were divided into two groups: IgG4-related Hashimoto's thyroiditis (24 cases) together with Riedel thyroiditis (1 case) and 171 non-IgG4-related thyroiditis. Compared to the non IgG4-related cases, IgG4-related thyroiditis showed a higher IgG4/IgG ratio (0.6 vs. 0.1, p < 0.0001), a higher median IgG4 count (45.2 vs. 6.2, p < 0.0001), an association with younger age (42.1 vs. 48.1 years, p = 0.036), and a lower female to-male ratio (11:1 vs. 17.5:1). Fibrous variant of Hashimoto's thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis. PMID- 26669780 TI - Cancer Patient-Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies. AB - PURPOSE: This study aimed to test the hypothesis that lung cancer patient-derived circulating microparticles (LCC-MPs) enhance metastatic lung tumors in a rat model. PROCEDURES: The controls (n = 6) and LCC-MP-treated rats (n = 6) with N1S1 induced pulmonary metastatic hepatocellular carcinoma (HCC) underwent dual-source CT (DSCT) on days 10, 15, and 20. Cellular and molecular studies were performed subsequently. RESULTS: DSCT revealed slow progression of metastatic lung tumors in the controls. Compared with the controls, the LCC-MP-treated rats exhibited significantly more and larger metastatic tumors on days 15 and 20 on DSCT, enhanced angiogenesis with higher microvessel count (CD34+), more CXCR4+ and VEGF+ cells in immunohistofluorescence studies, and higher protein expression levels of eNOS, angiopoietin, vascular endothelial growth factor, and CD31 on western blotting (Mann-Whitney test, all P < 0.05). CONCLUSIONS: LCC-MPs can elicit oncogenic stimulation and accelerate metastatic HCC growth in rat lung as demonstrated on DSCT and enhanced tumoral angiogenesis as confirmed in cellular and molecular studies. PMID- 26669781 TI - Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. AB - BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Currently, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate two new urinary biomarkers-insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in patients after coronary artery bypass surgery (CABG). METHODS: In a prospective cohort study, 60 consecutive patients undergoing isolated on-pump CABG were enrolled. Urine samples collected every 12 h in the postoperative course were analyzed for the product of TIMP-2 and IGFBP7. Urinary output, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded simultaneously. Primary clinical endpoint was the development of AKI stage 2 or 3 according to the classification of the KDIGO within 48 h after surgery. RESULTS: 48 male and 12 female patients with a mean age of 69.61 +/- 8.4 years were included. 19 patients developed an AKI (31.6 %), six patients met the endpoint with AKI 2 or 3 (10 %). Urinary [TIMP-2]*[IGFBP7] increased significantly as early as 4 h after CABG in patients with AKI 2/3 (1.83 +/- 2.15 vs. 0.23 +/- 0.45, p < 0.05) whereas serum creatinine did not increase until 48 h after surgery. The diagnostic accuracy of [TIMP 2]*[IGFBP7] on day one after surgery for the prediction of AKI 2/3 was significantly better (sensitivity 0.89, specificity 0.81, AUC 0.817, 95 % CI 0.622-1.0 SE 0.099, p = 0.022, cut-off 0.817) than for serum creatinine (AUC 0.359, sensitivity 0.50, specificity of 0.52, cut-off value 1.17 mg/dl) and eGFR. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] represents a sensitive and specific biomarker to predict moderate to severe AKI very early after CABG. Analyses from our ongoing larger study are necessary to confirm these findings and probably increase sensitivity and specificity. PMID- 26669783 TI - Severity of Acute Cholecystitis and Risk of Iatrogenic Bile Duct Injury During Cholecystectomy, a Population-Based Case-Control Study. AB - BACKGROUND: Acute cholecystitis is a common complication to gallstone disease. The relation between the severity of acute cholecystitis and risk of bile duct injury during cholecystectomy has not yet been addressed and is the main focus of this study. METHODS: All cases with iatrogenic bile duct injury during cholecystectomy, within the Lake Malaren region, Sweden, were identified through ICD procedure codes for biliary reconstruction within the Swedish Inpatient Register and matched to non-injured cholecystectomized controls. Information regarding perioperative variables was collected through medical record review. RESULTS: After review, 158 cases and 623 controls remained for analyses. Adjusted risk of bile duct injury was doubled among patients with acute cholecystitis (OR 1.97 95 % CI 1.05-3.72), whereas a mild acute cholecystitis (Tokyo grade I) did not affect the risk of bile duct injury (OR 0.96 95 % CI 0.41-2.25), a moderate (Tokyo grade II) more than doubled the risk (OR 2.41 95 % CI 1.21-4.80). Severe cholecystitis (Tokyo grade III) had a close to significant eightfold increase in risk (OR 8.43 95 % CI 0.97-72.9). The intention to use intraoperative cholangiography reduced injury risk by 52 % (OR 0.48, 95 % CI 0.29-0.81). CONCLUSIONS: Patients with on-going acute cholecystitis had twice the risk of sustaining a biliary lesion compared to patients without acute cholecystitis. There was a relation between the Tokyo guidelines severity grading of acute cholecystitis and injury risk and the intention to use intraoperative cholangiography halved the risk of reconstructed bile duct injury during cholecystectomy. PMID- 26669782 TI - A spontaneous metastasis model reveals the significance of claudin-9 overexpression in lung cancer metastasis. AB - Metastasis causes most cancer related mortality but the mechanisms governing metastatic dissemination are poorly defined. Metastasis involves egression of cancer cells from the primary tumors, their survival in circulation and colonization at the secondary sites. Cancer cell egression from the primary tumor is the least defined process of metastasis as experimental metastasis models directly seed cancer cells in circulation, thus bypassing this crucial step. Here, we developed a spontaneous metastasis model that retains the egression step of metastasis. By repeated in vivo passaging of the poorly metastatic Lewis lung carcinoma (3LL) cells, we generated a cell line (p-3LL) that readily metastasizes to lungs and liver from subcutaneous (s.c.) tumors. Interestingly, when injected intravenously, 3LL and p-3LL cells showed a similar frequency of metastasis. This suggests enhanced egression of p-3LL cells may underlie the enhanced metastatic spread from primary tumors. Microarray analysis of 3LL and p-3LL cells as well as the primary tumors derived from these cells revealed altered expression of several genes including significant upregulation of a tight junction protein, claudin-9. Increased expression of claudin-9 was confirmed in both p-3LL cells and tumors derived from these cells. Knockdown of claudin-9 expression in p-3LL cells by si-RNA significantly reduced their motility, invasiveness in vitro and metastasis in vivo. Conversely, transient overexpression of claudin-9 in 3LL cells enhanced their motility. These results suggest an essential role for claudin-9 in promoting lung cancer metastasis. PMID- 26669784 TI - Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC. AB - INTRODUCTION: Morbidity and mortality rates after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are important quality parameters to compare peritoneal surface malignancy centers. A major problem to assess postoperative outcomes among centers is the inconsistent reporting due to two coexisting systems, the diagnose-based common terminology criteria for adverse events (CTCAE) classification and the therapy-oriented Clavien-Dindo classification. We therefore assessed and compared both reporting systems. PATIENTS AND METHODS: Complications after CRS/HIPEC were recorded in 147 consecutive patients and independently graded by an expert board using both systems. In a next step, a group of residents, experienced surgeons, and medical oncologists evaluated a set of twelve real complications, either with the Clavien Dindo or CTCAE classification. RESULTS: The postoperative complication rate after CRS/HIPEC was 37 % (54/147), 6.8 % (10/147) were reoperated, and three (2 %) patients died. The most frequent complications were intestinal fistula or abscess, pulmonary complications, and ileus. Grading of complications with the CTCAE classification resulted in a significantly higher major morbidity rate compared to the Clavien-Dindo classification (25 vs. 8 %, p = 0.001). Evaluating a set of complications, residents, surgeons, and oncologists correctly assessed significantly more complications with the Clavien-Dindo compared to the CTCEA classification (p < 0.001). In addition, all participants evaluated the Clavien Dindo classification as more simple. Residents (p < 0.001) and surgeons (p < 0.01) required less time with the Clavien-Dindo classification; there was no difference for oncologist. CONCLUSION: In conclusion, our data indicate that there is a different interpretation of severity grades of complications after CRS/HIPEC between the two classifications. There is a need for a common language in the field of CRS/HIPEC, which should be defined by a new consensus to compare surgical outcomes. PMID- 26669785 TI - Inequitable Access to Timely Cleft Palate Surgery in Low- and Middle-Income Countries. AB - BACKGROUND: Delayed cleft palate repair has significant implications for physical, mental, and social well-being and has been suggested to lead to an increased risk of infant and under-five mortality in low- and middle-income countries (LMICs). METHODS: Using medical records from Operation Smile international programs taking place in eleven different LMICs between March and May 2014, we performed a logistic regression assessing the relationship between delayed surgery access, defined as primary palatoplasty presentation after 24 months of age, and GDP per capita across 11 countries. RESULTS: Median age of presentation ranged from 13 to 24 months in upper-middle-income countries, 17 to 35 months in lower-middle-income countries, and 14 to 66 months in low-income countries. Our analysis demonstrated a 14 % increase in the odds of late surgery [OR = 0.88 (P < 0.001)] for every 1000 USD decrease of GDP per capita. In low- and lower-middle-income countries, this relationship was even stronger, with an OR of 0.59 (P < 0.001), indicating a 70 % increase in the odds of late surgery for every 1000 USD decrease in GDP per capita. CONCLUSIONS: There is a strong negative correlation between national income status and delayed access to primary cleft palate surgery, indicating a high degree of inequity in access to surgery, particularly in low- and lower-middle-income countries. As the importance of surgery in global health is increasingly recognized, an equity perspective must be included in the global dialog to ensure that the world's poor have fair and equitable access to essential surgical care. PMID- 26669786 TI - First Episode of Spontaneous Pneumothorax: CT-based Scoring to Select Patients for Early Surgery. AB - BACKGROUND: Although recurrence of primary spontaneous pneumothorax (PSP) is frequent, guidelines do not routinely recommend surgery after first presentation. A CT-based lung dystrophy severity score (DSS) has recently been proposed to predict recurrence following conservative therapy. This study compares the DSS in surgically and conservatively treated patients. METHODS: This is a retrospective analysis of first episode PSP patients, comparing video-assisted thoracic surgery (VATS; group A) to conservative treatment with or without chest drainage (group B). CT scans were reviewed for blebs or bullae, and patients were assigned DSS values and stratified into risk groups (low and high-grade). Primary end point was ipsilateral or contralateral recurrence. RESULTS: Fifty-six patients were included, 33 received VATS and 23 conservative treatment. In total, 37.5 % experienced recurrence, with a 5-year estimated recurrence rate of 40.7 % (group A: 13.3 %; group B: 73.9 %; p < 0.001). In group B, detection of any dystrophic lesions resulted in significantly higher 5-year recurrence rates (86.7 vs. 50.0 %; p = 0.03), there was no significant difference in group A (17.7 vs. 7.7 %; p = 0.50). Greater DSS values correlated with higher 5-year recurrence rates in group B (p = 0.02), but not in group A (p = 0.90). Comparing low- and high-grade patients in group B resulted in a significant 5-year recurrence rate of 53.8 versus 100 % (p = 0.023). CONCLUSIONS: The DSS is useful to indicate VATS after the first episode. For routine application, assigning patients to low- and high grade groups seems most practical. We recommend CT-evaluation for every PSP patient and early surgery for those with lesions exceeding one bleb. After VATS, the preoperative DSS is not beneficial in predicting recurrence. PMID- 26669788 TI - Economic Valuation of the Global Burden of Cleft Disease Averted by a Large Cleft Charity. AB - BACKGROUND: This study attempts to quantify the burden of disease averted through the global surgical work of a large cleft charity, and estimate the economic impact of this effort over a 10-year period. METHODS: Anonymized data of all primary cleft lip and cleft palate procedures in the Smile Train database were analyzed and disability-adjusted life years (DALYs) calculated using country specific life expectancy tables, established disability weights, and estimated success of surgery and residual disability probabilities; multiple age weighting and discounting permutations were included. Averted DALYs were calculated and gross national income (GNI) per capita was then multiplied by averted DALYs to estimate economic gains. RESULTS: 548,147 primary cleft procedures were performed in 83 countries between 2001 and 2011. 547,769 records contained complete data available for the study; 58 % were cleft lip and 42 % cleft palate. Averted DALYs ranged between 1.46 and 4.95 M. The mean economic impact ranged between USD 5510 and 50,634 per person. This corresponded to a global economic impact of between USD 3.0B and 27.7B USD, depending on the DALY and GNI values used. The estimated cost of providing these procedures based on an average reimbursement rate was USD 197M (0.7-6.6 % of the estimated impact). CONCLUSIONS: The immense economic gain realized through procedures focused on a small proportion of the surgical burden of disease highlights the importance and cost-effectiveness of surgical treatment globally. This methodology can be applied to evaluate interventions for other conditions, and for evidence-based health care resource allocation. PMID- 26669787 TI - Molecular Characteristics of Large Parathyroid Adenomas. AB - INTRODUCTION: The clinical entity of large parathyroid adenomas (LPTAs) has not been well defined. It is speculated that LPTAs would have biochemical, histological, and molecular characteristics different from small adenomas. Our study aimed to find out occurrence of atypia and carcinomas in large parathyroid lesions and the presence of distinct molecular abnormalities in LPTAs. MATERIALS AND METHODS: We divided the parathyroid lesions into large (>7 g, i.e., LPTAs) and small (<7 g) adenomas. We performed parafibromin, APC (adenomatous polyposis coli), galectin 3, and PGP9.5 (protein gene product 9.5) analysis by immunohistochemistry in adenomas without atypia, atypical adenomas, and carcinomas. RESULTS: Mean serum calcium, alkaline phosphatase, and intact PTH were significantly higher in large parathyroid tumor group. The presence of both atypical adenoma and carcinoma was higher in large parathyroid tumor group. There was higher percentage of atypia in patients with LPTAs >10 g (33%), and 68% of tumors showed at least one marker suggestive of malignancy in this group. Detailed analysis of immunohistochemical features of LPTA >10 g revealed that six patients showed complete loss of parafibromin immunoreactivity (out of these four showed atypia), while seven showed partial loss. In histopathologically proven malignancy (n = 9), six patients showed complete loss of parafibromin staining, 5 (55%) APC negativity, and 45% showed both galectin 3 and PGP9.5 positivity. Three out of these showed all IHC markers s/o malignancy, and all of them had evidence of metastases or recurrence. 32% of atypical adenoma and 13% of atypical adenoma showed complete loss of parafibromin staining, however none developed metastases or recurrence in follow-up (median follow-up 40 months). Loss of parafibromin staining (complete or partial) was higher in LPTA group (56%) than that in small adenoma (39%); however, it was not statistically significant. APC, galectin 3, and PGP9.5 markers suggestive were higher in LPTA group but were not significant. CONCLUSION: LPTAs may show some morphological and immunohistochemical features suggestive of malignancy and can be considered a separate entity. However, the immunohistochemical markers are unable to clearly segregate those LPTAs that may show premalignant potential. Further, we would like to recommend that LPTAs showing complete parafibromin loss together with atypia should be kept under close follow-up. PMID- 26669789 TI - Ligand-Binding Assay Development: What Do You Want to Measure Versus What You Are Measuring? PMID- 26669790 TI - Effect of hemodiafiltration therapy in a low-birthweight infant with congenital sepsis. AB - The clinical course of congenital neonatal sepsis due to Streptococcus pneumoniae progresses rapidly and results in multiorgan failure with high mortality. The swift progression of the disease limits the timeframe for conventional treatment, which often requires waiting for antibiotics to show efficacy. Here, we describe the case of a very low-birthweight (VLBW) female infant with congenital sepsis due to S. pneumoniae who was treated with continuous hemodiafiltration (CHDF) and polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP). The infant was born at 30 weeks' gestation and diagnosed with hypotension, disseminated intravascular coagulation, and pulmonary hypertension. CHDF and PMX-DHP were initiated approximately 11 h after birth. Mean blood pressure, oxygenation, and blood interleukin-6 began to improve after dialysis commencement, and the patient survived with mild sequelae. Combined CHDF and PMX-DHP may be effective in treating VLBW infants with severe septic shock. PMID- 26669791 TI - Patient Experiences of Men Who Have Sex with Men Using Pre-Exposure Prophylaxis to Prevent HIV Infection. PMID- 26669792 TI - Hepatitis C Direct Acting Antiviral Therapies in a New York City HIV/AIDS Special Needs Plan: Uptake and Barriers. PMID- 26669793 TI - The Influence of Trust in Physicians and Trust in the Healthcare System on Linkage, Retention, and Adherence to HIV Care. AB - Lack of trust by the patient in the physicians or the healthcare system has been associated with poorer health outcomes. The present study was designed to determine if trust in physicians and the healthcare system among persons newly diagnosed with HIV infection was predictive of patients' subsequent linkage, retention, and adherence to HIV care. 178 newly diagnosed HIV infected patients were administered the trust-in-physicians and trust-in-healthcare system scales. Median trust-in-physicians and trust-in-healthcare system scores were compared for all the mentioned subsequent linkage, retention, and adherence to HIV care. Univariate logistic regression using the trust-in-physician scale confirmed significant association with retention in care (p = 0.04), which persisted in multivariate analyses (p = 0.04). No significant association was found between trust-in-physicians and linkage to care or adherence to antiretroviral therapy. Trust in the healthcare system was not associated with any of the outcomes. Patients with higher trust in physicians were more likely to be retained in HIV care. Trust at diagnosis may not be a barrier to better clinical outcomes, either because trust changes based on subsequent interactions, or because trust is not a determining feature. Interventions to improve retention in care could include improving trust in physicians or target persons with low trust in physicians. PMID- 26669794 TI - Association between p53 status, human papillomavirus infection, and overall survival in advanced oral cancer after resection and combination systemic treatment. AB - Our previous study on 75 cases of advanced oral squamous cell carcinomas (SCC) treated by neoadjuvant chemotherapy, radical surgery, and radiotherapy showed that overexpression of p53 of more than 50% indicated a strong probability of genetic mutation, and tumours that are characterised by this p53 pattern respond poorly to treatment and have a poor prognosis (p= 0.0001). We have studied the same cohort of patients retrospectively to investigate the incidence of human papillomavirus-16 (HPV16) infection, the relation to the overexpression or mutation of the p53 gene, and the association with overall survival. There were 57 men and 18 women, mean age 67 (range 57-72) years. HPV16 infectivity was found in 66 patients (88%) - 49/57 men (86%) and 17/18 women (94%). There was no significant difference between the sexes (p=0.32). The cumulative survival of the entire group after a follow-up of 38 months was 26% (SE 6.4). The log rank test indicated that the combination of HPV-16 infectivity and p53mutation was significantly related to prognosis (p=0.000). On the other hand HPV16 infectivity alone was not significantly related to prognosis (p=0.78) The incidence of HPV-16 infection decreased with increasing immune p53 expression (p=0.005), whereas that of the HPV16+p53mutation combination increased with increasing immune p53 expression (p=0.000). The results show the importance of the investigation of HPV and p53 expression to define prognosis in oral SCC. PMID- 26669795 TI - Online and In-Person Nutrition Education Improves Breakfast Knowledge, Attitudes, and Behaviors: A Randomized Trial of Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children. AB - BACKGROUND: Although in-person education is expected to remain central to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) service delivery, effective online nutrition education has the potential for increased exposure to quality education and a positive influence on nutrition behaviors in WIC participants. Education focused on promoting healthy breakfast behaviors is an important topic for WIC participants because breakfast eating compared with breakfast skipping has been associated with a higher-quality diet and decreased risk for obesity. OBJECTIVE: To examine the influences of online and in-person group nutrition education on changes in knowledge, attitudes, and behaviors related to breakfast eating. DESIGN: Randomized-controlled trial comparing the effectiveness of online and in-person nutrition education between March and September 2014. PARTICIPANTS/SETTING: Five hundred ninety WIC participants from two Los Angeles, CA, WIC clinics were randomly assigned to receive in-person group education (n=359) or online education (n=231). Education focused on ways to reduce breakfast skipping and promoted healthy options at breakfast for parents and their 1- to 5-year-old children participating in WIC. Questionnaires assessing breakfast-related knowledge, attitudes, and behaviors were administered before and after education, and at a 2- to 4-month follow-up. STATISTICAL ANALYSIS: Changes within and between in-person and online groups were compared using t tests and chi(2) tests. Analysis of covariance and generalized estimating equations were used to assess differences in change between groups. RESULTS: Changes in knowledge between pretest and follow-up at 2 to 4 months were similar between groups. Both groups reported reductions in barriers to eating breakfast due to time constraints, not having enough foods at home, and difficulty with preparation. Increases in the frequency of eating breakfast were greater for both the parent (P=0.0007) and child (P=0.01) in the online group compared with the in-person group during the same time points. CONCLUSIONS: Overall, this study demonstrates that both in-person and online nutrition education were effective in increasing breakfast-related knowledge in WIC participants, reducing breakfast skipping, and improving other breakfast-related behaviors, showing the potential usefulness for online education modalities for future WIC services. PMID- 26669796 TI - Autoimmunity in dengue: Literature review. PMID- 26669797 TI - Endothelial cell tolerance to lipopolysaccharide challenge is induced by monophosphoryl lipid A. AB - Prior exposure to lipopolysaccharide (LPS) produces a reduced or "tolerant" inflammatory response to subsequent challenges with LPS, however the potent pro inflammatory effects of LPS limit its clinical benefit. The adjuvant monophosphoryl lipid A (MPLA) is a weak toll-like receptor 4 (TLR4) agonist that induces negligible inflammation but retains potent immunomodulatory properties. We postulated that pre-treatment with MPLA would inhibit the inflammatory response of endothelial cells to secondary LPS challenge. Human umbilical vein endothelial cells (HUVECs), were exposed to MPLA (10 MUg/ml), LPS (100 ng/ml) or vehicle control. HUVECs were then washed and maintained in culture for 24 h before being challenged with LPS (100 ng/ml). Supernatants were collected and examined for cytokine production in the presence or absence of siRNA inhibitors of critical TLR4 signalling proteins. Pre-treatment with MPLA attenuated interleukin (IL)-6 production to secondary LPS challenge to a similar degree as LPS. The application of myeloid differentiation primary response gene 88 (MyD88) siRNA dramatically reduced MPLA-induced tolerance while TIR-domain-containing adapter-inducing interferon-beta (TRIF) siRNA had no effect. The tolerant phenotype in endothelial cells was associated with reduced IkappaB kinase (IKK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation and enhanced IL-1 receptor associated kinase-M (IRAK-M) expression for LPS-primed HUVECs, but less so in MPLA primed cells. Instead, MPLA-primed HUVECs demonstrated enhanced p extracellular-signal-regulated kinase (ERK) phosphorylation. In contrast with leucocytes in which tolerance is largely TRIF-dependent, MyD88 signalling mediated endotoxin tolerance in endothelial cells. Most importantly, MPLA, a vaccine adjuvant with a wide therapeutic window, induced tolerance to LPS in endothelial cells. PMID- 26669798 TI - TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding site. AB - Telomerase is a key component of the telomere length maintenance system in the majority of eukaryotes. Telomerase displays maximal activity in stem and cancer cells with high proliferative potential. In humans, telomerase activity is regulated by various mechanisms, including the interaction with telomere ssDNA overhangs that contain a repetitive G-rich sequence, and with noncoding RNA, Telomeric repeat-containing RNA (TERRA), that contains the same sequence. So these nucleic acids can compete for telomerase RNA templates in the cell. In this study, we have investigated the ability of different model substrates mimicking telomere DNA overhangs and TERRA RNA to compete for telomerase in vitro through a previously developed telomerase inhibitor assay. We have shown in this study that RNA oligonucleotides are better competitors for telomerase that DNA ones as RNA also use an alternative binding site on telomerase, and the presence of 2'-OH groups is significant in these interactions. In contrast to DNA, the possibility of forming intramolecular G-quadruplex structures has a minor effect for RNA binding to telomerase. Taking together our data, we propose that TERRA RNA binds better to telomerase compared with its native substrate - the 3'-end of telomere DNA overhang. As a result, some specific factor may exist that participates in switching telomerase from TERRA to the 3'-end of DNA for telomere elongation at the distinct period of a cell cycle in vivo. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669799 TI - Associations of serum adiponectin with markers of cardio-metabolic disease risk in Indigenous Australian adults with good health, diabetes and chronic kidney disease. AB - : The higher serum adiponectin concentrations observed in females are often attributed to differences in adiposity or sex hormones. There is little data describing adiponectin in Indigenous Australians, and no studies examining its association with cardio-metabolic disease risk markers and chronic kidney disease (CKD). AIM: To describe the relationship of serum adiponectin with cardio metabolic disease risk markers and kidney function in a community-based sample of Indigenous Australian adults, with particular reference to sex-specific differences. METHODS: A cross-sectional analysis of a community-based volunteer sample of 548 Indigenous Australian adults (62% female), stratified into five cardio-metabolic risk groups ranging from good health (strata-1) to high cardio metabolic risk and low measured glomerular filtration rate (mGFR, <60ml/min/1.73m2) (strata-5). We examined serum adiponectin concentrations with cardio-metabolic risk markers, albuminuria and mGFR. RESULTS: Indigenous Australian females had a lower than expected adiponectin concentration (3.5MUg/ml), which was higher than males in strata 1-4 (as in other populations), but not in strata-5 (mGFR<60, p=0.19), and higher leptin: adiponectin ratio than other populations (7.8ng/MUg - strata-1, healthy females; 12.2ng/MUg - strata-3, females with diabetes and mGFR>=90). Female-gender, HDL-cholesterol (positive), mGFR and waist: hip ratio (WHR) (inverse) were independently associated with log adiponectin when mGFR>=60; when mGFR<60, female-gender was associated with 0.27 units lower log-adiponectin. CONCLUSION: Female-gender was not associated with higher adiponectin concentrations in Indigenous Australians with mGFR<60ml/min/1.73m2. High WHR was frequent in both genders, and inversely associated with adiponectin. Longitudinal studies are needed to examine relationships of serum adiponectin, obesity and cardiovascular disease events in Indigenous Australians. PMID- 26669801 TI - Bacillomycin D and its combination with amphotericin B: promising antifungal compounds with powerful antibiofilm activity and wound-healing potency. AB - AIMS: In this study, we evaluated the ability of the lipopeptide bacillomycin D and the antifungal drug amphotericin B as well as their combination, to inhibit Candida albicans biofilm formation and to accelerate keratinocyte cell migration. METHODS AND RESULTS: The antibiofilm activity of bacillomycin D and its combination with amphotericin B was carried out by crystal violet colorimetric method. Our results have shown that, when combined together at low concentrations nontoxic to mammalian cells, corresponding to 1/32 MIC (0.39 MUg ml(-1) ) and 1/4 MIC (0.06 MUg ml(-1) ) for bacillomycin D and amphotericin B, respectively, a clear antibiofilm activity is manifested (95% inhibition of biofilm formation) along with a clear inhibition of germ tube formation. Moreover, the effect of both drugs on preformed biofilm of C. albicans strain was determined using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The combination of the two antifungal compounds at 0.39 and 1 MUg ml(-1) for bacillomycin D and amphotericin B, respectively, resulted in a clear enhancement of biofilm eradication compared to the results obtained with each drug alone. Furthermore, this combination was found to promote the closure of a gap produced in a monolayer of human keratinocytes. CONCLUSIONS: Bacillomycin D and its combination with amphotericin B display impressive anti-biofilm and wound-healing activities. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of the lipopeptide bacillomycin D and the antifungal drug amphotericin B in medical devices may offer a promising alternative for topical treatment of Candida-associated infections in the setting of a wound. PMID- 26669802 TI - On the importance of developing a new generation of breath tests for Helicobacter pylori detection. AB - State-of-the-art methods for non-invasive detection of the Helicobacter pylori (H. pylori) infection have been considered. A reported global tendency towards a non-decreasing prevalence of H. pylori worldwide could be co-influenced by the functional limitations of urea breath tests (UBTs), currently preferred for the non-invasive recognition of H. pylori in a clinical setting. Namely, the UBTs can demonstrate false-positive or false-negative results. Within this context, limitations of conventional clinically exploited H. pylori tests have been discussed to justify the existing need for the development of a new generation of breath tests for the detection of H. pylori and the differentiation of pathogenic and non-pathogenic strains of the bacterium. This paper presents the results of a pilot clinical study aimed at evaluating the development and diagnostic potential of a new method based on the detection of the non-urease products of H. pylori vital activity in exhaled gas. The characteristics of breath of adolescents with H. pylori-positive and H. pylori-negative functional dyspepsia, together with a consideration of the cytotoxin-associated gene A (CagA) status of H. pylori positive subjects, have been determined for the first time using innovative point contact nanosensor devices based on salts of the organic conductor tetracyanoquinodimethane (TCNQ). The clinical and diagnostic relevance of the response curves of the point-contact sensors was assessed. It was found that the recovery time of the point-contact sensors has a diagnostic value for differentiation of the H. pylori-associated peptic ulcer disease. The diagnostically significant elongation of the recovery time was even more pronounced in patients infected with CagA-positive H. pylori strains compared to the CagA-negative patients. Taking into account the operation of the point contact sensors in the real-time mode, the obtained results are essential prerequisites for the development of a fast and portable breath test for non invasive detection of cytotoxic CagA strains of H. pylori infection. The relaxation time of the point-contact nanosensors could be selected as a diagnostic criterion for non-invasive determination of H. pylori-associated destructive lesions of the gastroduodenal area in adolescents, using the point contact spectroscopic concept of breath analysis. This can subsequently be implemented into a 'test-and-treat' approach for the management of uninvestigated dyspepsia in populations with a high prevalence of H. pylori (according to the Maastricht III and IV Consensus recommendations). PMID- 26669800 TI - ACAT1/SOAT1 as a therapeutic target for Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common cause of dementia with no cure at present. Cholesterol metabolism is closely associated with AD at several stages. ACAT1 converts free cholesterol to cholesteryl esters, and plays important roles in cellular cholesterol homeostasis. Recent studies show that in a mouse model, blocking ACAT1 provides multiple beneficial effects on AD. Here we review the current evidence that implicates ACAT1 as a therapeutic target for AD. We also discuss the potential usage of various ACAT inhibitors currently available to treat AD. PMID- 26669803 TI - Do Physically Active Patients Have Better Functional Outcome after Stroke? A Systematic Review. AB - BACKGROUND AND PURPOSE: Stroke is one of the major causes of mortality and, among survivors, disability. Physical activity has a protective effect maybe due to a major control of risk factors, such as hypertension, diabetes mellitus, and body weight. However, the effect of prestroke physical activity and the poststroke functional outcomes needs clarification. METHODS: We made a systematic review of the literature to elucidate this effect through electronic search in the MEDLINE/PubMed database. Prisma statement was used as a basis for this systematic review and analysis of the risk of bias was made according to the Grading of Recommendations, Assessment, Development and Evaluation. Three studies were finally analyzed in this review. RESULTS: The largest of the studies (Rist et al) revealed no association between prior physical activity and functional outcome after stroke. The second major study (Stroud et al) showed only a slight association. Only the smallest of the 3 studies (Krarup et al) showed a protective effect of physical activity. CONCLUSIONS: The evidence of the protective effect of physical activity is still conflicting. Better longitudinal studies are still needed to see the real effect of physical activity on functional outcome after stroke. PMID- 26669804 TI - Knockdown of GPR137,G Protein-coupled receptor 137, Inhibits the Proliferation and Migration of Human Prostate Cancer Cells. AB - GPR137 belongs to the G protein-coupled receptor family involving the regulation of transmembrane signal transduction that launches pivotal cellular functions. However, its function in prostate cancer (PCa) has been rarely reported. It was found in this study that GPR137 was upregulated in PCa tissues as compared with that in paracancerous tissues. To see whether GPR137 could serve as a potential therapeutic target for PCa, GPR137 was knocked down to verify its biological function in PCa cells. Lentivirus-introduced short hairpin RNA (shRNA) was designed to silence GPR137 gene. It was found that silencing of GPR137 gene suppressed the proliferation and colony formation of PCa cell lines PC-3 and DU145. Further study indicated that growth inhibition by GPR137 knockdown was associated with cell cycle arrest at G0/G1 phase. Furthermore, silencing of GPR137 repressed the invasion and migration abilities of PC-3 cells via downregulating slug and snail and upregulating E-cadherin. Collectively, these findings imply that GPR137 plays an important role in the occurrence and progression of PCa and may prove to be a potential therapeutic target for the treatment of advanced PCa. PMID- 26669805 TI - Three-Dimensional Echocardiography in the Evaluation of Right Ventricular Global and Regional Systolic Function in Patients with Atrial Septal Defect before and after Percutaneous Closure. AB - OBJECTIVE: To evaluate right ventricular (RV) global and regional systolic function in patients with atrial septal defect (ASD) before and after percutaneous closure using real time three-dimensional echocardiography (RT3DE). METHODS: RT3DE was performed in 81 patients with ASD within 24 hours before and after percutaneous closure to obtain RV global and regional ejection fraction (EF) in three compartments (inflow, body, and outflow). RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), peak tricuspid systolic velocity (S), and pulmonary vascular resistance (PVR) were recorded. Forty matched normal adults were included as controls. RESULTS: When compared with controls, RV global and regional EF were decreased in preclosure patients (P < 0.001). FAC was lower while TAPSE and S were higher in preclosure patients than in controls (P < 0.05). After closure, RV systolic function parameters were all reduced (P < 0.001). Regional EF in the body compartment was the lowest among the three compartments in ASD patients (P < 0.05). Procedural percentage changes of RV global EF and regional EF in the inflow compartment were lower than those of two-dimensional systolic function parameters (P < 0.05). RV global and regional EF in the inflow compartment were negatively correlated with PVR in patients after closure (r = -0.601, -0.543, P < 0.001). CONCLUSIONS: RV global and regional systolic functions are impaired in open and closed ASD. RT3DE-derived systolic function parameters are negatively correlated with RV after load. RT3DE has potential value in the evaluation of RV systolic function in patients with ASD. PMID- 26669806 TI - A pharmacokinetic and residual study of sulfadiazine/trimethoprim in mandarin fish (Siniperca chuatsi) with single- and multiple-dose oral administrations. AB - A pharmacokinetic and tissue residue study of sulfadiazine combined with trimethoprim (SDZ/TMP = 5/1) was conducted in Siniperca chuatsi after single- (120 mg/kg) or multiple-dose (an initial dose of 120 mg/kg followed by a 5-day consecutive dose of 60 mg/kg) oral administrations at 28 degrees C. The absorption half-life (t1/2alpha ), elimination half-life (t1/2beta ), volume of distribution (Vd /F), and the total body clearance (ClB /F) for SDZ and TMP were 4.3 +/- 1.7 to 6.3 +/- 1.8 h and 2.4 +/- 1.0 to 3.9 +/- 0.9 h, 25.9 +/- 4.5 to 53.0 +/- 5.6 h and 11.8 +/- 3.5 to 17.1 +/- 3.4 h, 2.34 +/- 0.78 to 3.67 +/- 0.99 L/kg and 0.39 +/- 0.01 to 1.33 +/- 0.57 L/kg, and 0.03 +/- 0.01 to 0.06 +/- 0.01 L/kg.h and 0.02 +/- 0.01 to 0.05 +/- 0.01 L/kg.h, respectively, after the single dose. The elimination half-life (t1/2beta ) and mean residue time (MRT) for SDZ and TMP were 68.8 +/- 7.8 to 139.8 +/- 12.3 h and 34.0 +/- 5.5 to 56.1 +/- 6.8 h, and 99.3 +/- 6.1 to 201.7 +/- 11.5 h and 49.1 +/- 3.5 to 81.0 +/- 5.1 h, respectively, after the multiple-dose administration. The daily oral SDZ/TMP administration might cause a high tissue concentration and long t1/2beta , thereby affecting antibacterial activity. The withdrawal time for this oral SDZ/TMP formulation (according to the accepted guidelines in Europe for maximum residue limits, <0.1 mg/kg of tissues for sulfonamides, and <0.05 mg/kg for TMP) should not be <36 days for fish. PMID- 26669807 TI - Melanotic Neuroectodermal Tumor of Infancy Presenting with Fast Growing Scrotal Swelling: A Case Report and Literature Review. AB - Testicular melanotic neuroectodermal tumor of infancy (MNTI) is extremely rare, with 2 cases reported in the literature. Its rarity, rapid and infiltrative growth pattern pose a diagnostic challenge. A previously healthy 3-month old male, presented with a history of worsening left hemiscrotal swelling for one week. An outside ultrasound was suggestive of testicular torsion. Left orchiectomy demonstrated a mass occupying almost entire testicle with a variegated cut surface, with areas of pigmentation, necrosis and hemorrhage. Histological examination confirmed MNTI of the testis and epididymis. MNTI should be included in differential diagnosis in infants presenting with fast growing scrotal swelling. PMID- 26669808 TI - In response to "Preliminary development of an ultrabrief two-item bedside test for delirium". PMID- 26669809 TI - Increasing Electrochemiluminescence Intensity of a Wireless Electrode Array Chip by Thousands of Times Using a Diode for Sensitive Visual Detection by a Digital Camera. AB - Both a wireless electrochemiluminescence (ECL) electrode microarray chip and the dramatic increase in ECL by embedding a diode in an electromagnetic receiver coil have been first reported. The newly designed device consists of a chip and a transmitter. The chip has an electromagnetic receiver coil, a mini-diode, and a gold electrode array. The mini-diode can rectify alternating current into direct current and thus enhance ECL intensities by 18 thousand times, enabling a sensitive visual detection using common cameras or smart phones as low cost detectors. The detection limit of hydrogen peroxide using a digital camera is comparable to that using photomultiplier tube (PMT)-based detectors. Coupled with a PMT-based detector, the device can detect luminol with higher sensitivity with linear ranges from 10 nM to 1 mM. Because of the advantages including high sensitivity, high throughput, low cost, high portability, and simplicity, it is promising in point of care testing, drug screening, and high throughput analysis. PMID- 26669810 TI - Spatial distribution of nominally herbivorous fishes across environmental gradients on Brazilian rocky reefs. AB - Assemblages of roving herbivores were consistently different between eastern, warmer, sheltered sites and western, colder, more wave-exposed sites. At eastern sites, detritivorous-herbivorous species dominated while omnivores had the highest biomass and were dominant at western sites. Macroalgivores did not show any trends related to location. These distributional patterns, at relatively small spatial scales of a few kilometres, mirror large-scale latitudinal patterns observed for the studied species along the entire Brazilian coast, where cold water associated species are abundant on south-eastern rocky reefs (analogous to the western sites of this study), and tropical species are dominant on north eastern coral reefs (analogous to the eastern sites). Species-level analyses demonstrated that depth was an important factor correlated with biomasses of Diplodus argenteus, Sparisoma axillare and Sparisoma tuiupiranga, probably due to resource availability and interspecific competition. Herbivorous fish assemblages in the study area have been historically affected by fishing, and combined with the variation in assemblage structure, this is likely to have important, spatially variable effects on the dynamics of benthic communities. PMID- 26669811 TI - Iron Deficiency in Heart Failure: Looking Beyond Anaemia. AB - Iron is an essential micronutrient in many cellular processes. Iron deficiency, with or without anaemia, is common in patients with chronic heart failure. Observational studies have shown iron deficiency to be associated with worse clinical outcomes and mortality. The treatment of iron deficiency in chronic heart failure patients using intravenous iron alone has shown promise in several clinical trials, although further studies which include larger populations and longer follow-up times are needed. PMID- 26669812 TI - Management of Prosthetic Valve Thrombosis Complicated with Coronary Embolism. PMID- 26669813 TI - Cost-effectiveness of a Population-based Lifestyle Intervention to Promote Healthy Weight and Physical Activity in Non-attenders of Cardiac Rehabilitation. AB - BACKGROUND: To evaluate the long-term cost-effectiveness of two home-based cardiac rehabilitation (CR) interventions (Healthy Weight (HW) and Physical Activity (PA)) for patients with cardiovascular disease (CVD), who had been referred to cardiac rehabilitation (CR) but had not attended. The interventions consisted of pedometer-based telephone coaching sessions on weight, nutrition and physical activity (HW group) or physical activity only (PA group) and were compared to a control group who received information brochures about physical activity. METHODS: A cost-effectiveness analysis was conducted using data from two randomised controlled trials. One trial compared HW to PA (PANACHE study), and the second compared PA to usual care. A Markov model was developed which used one risk factor, body mass index (BMI) to determine the CVD risk level and mortality. Patient-level data from the trials were used to determine the transitions to CVD states and healthcare related costs. The model was run for separate cohorts of males and females. Univariate and probabilistic sensitivity analysis were conducted to test the robustness of the results. RESULTS: Given a willingness-to-pay threshold of $50,000/QALY, in the long run, both the HW and PA interventions are cost-effective compared with usual care. While the HW intervention is more effective, it also costs more than both the PA intervention and the control group due to higher intervention costs. However, the HW intervention is still cost-effective relative to the PA intervention for both men and women. Sensitivity analysis suggests that the results are robust. CONCLUSION: The results of this paper provide evidence of the long-term cost-effectiveness of home-based CR interventions for patients who are referred to CR but do not attend. Both the HW and PA interventions can be recommended as cost-effective home-based CR programs, especially for people lacking access to hospital services or who are unable to participate in traditional CR programs. PMID- 26669814 TI - Associations of Perceived Stress, Resilience and Social Support with Sleep Disturbance Among Community-dwelling Adults. AB - Sleep disturbance is often described as sleeping poorly, difficulty falling asleep and maintaining sleep, and waking early. Currently, most studies examining sleep disturbance have focused on negative psychological variables; however, few studies have combined both negative and positive psychosocial factors to assess sleep. The aim of this study was to investigate the prevalence of sleep disturbance and psychosocial correlates in Chinese community-dwelling adults. A total of 1471 adults, between 18 and 60 years old, from eight selected community settings in Jinan, China, were surveyed using the Pittsburgh Sleep Quality Index, Perceived Stress Scale, 10-item Connor-Davidson Resilience Scale and Multidimensional Scale of Perceived Social Support and provided sociodemographic information. We found that the prevalence of sleep disturbance was 33.9%. After adjusting for age, employment status and physical co-morbidity, perceived stress was significantly associated with sleep disturbance [odds ratio (OR) = 1.14, p < 0.001], while resilience and social support were associated with a low likelihood of sleep disturbance (OR = 0.90, p < 0.001; OR = 0.97, p < 0.001). Furthermore, regression analysis showed that the interaction between perceived stress and resilience was significant (p < 0.05). Resilience buffered the negative impact of perceived stress on sleep disturbance. Given the close relationship between sleep disturbance and psychosocial correlates, the development of effective intervention programmes to improve sleep quality in this population should be considered. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26669815 TI - Methane and Nitrous Oxide Emissions Reduced Following Conversion of Rice Paddies to Inland Crab-Fish Aquaculture in Southeast China. AB - Aquaculture is an important source of atmospheric methane (CH4) and nitrous oxide (N2O), while few direct flux measurements are available for their regional and global source strength estimates. A parallel field experiment was performed to measure annual CH4 and N2O fluxes from rice paddies and rice paddy-converted inland crab-fish aquaculture wetlands in southeast China. Besides N2O fluxes dependent on water/sediment mineral N and CH4 fluxes related to water chemical oxygen demand, both CH4 and N2O fluxes from aquaculture were related to water/sediment temperature, sediment dissolved organic carbon, and water dissolved oxygen concentration. Annual CH4 and N2O fluxes from inland aquaculture averaged 0.37 mg m(-2) h(-1) and 48.1 MUg m(-2) h(-1), yielding 32.57 kg ha(-1) and 2.69 kg N2O-N ha(-1), respectively. The conversion of rice paddies to aquaculture significantly reduced CH4 and N2O emissions by 48% and 56%, respectively. The emission factor for N2O was estimated to be 0.66% of total N input in the feed or 1.64 g N2O-N kg(-1) aquaculture production in aquaculture. The conversion of rice paddies to inland aquaculture would benefit for reconciling greenhouse gas mitigation and agricultural income increase as far as global warming potentials and net ecosystem economic profits are of concomitant concern. Some agricultural practices such as better aeration and feeding, and fallow season dredging would help to lower CH4 and N2O emissions from inland aquaculture. More field measurements from inland aquaculture are highly needed to gain an insight into national and global accounting of CH4 and N2O emissions. PMID- 26669816 TI - ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo. AB - Adenosine deaminases bind double stranded RNA and convert adenosine to inosine. Editing creates multiple isoforms of neurotransmitter receptors, such as with Gria2. Adar2 KO mice die of seizures shortly after birth, but if the Gria2 Q/R editing site is mutated to mimic the edited version then the animals are viable. We performed RNA-Seq on frontal cortices of Adar2(-/-) Gria2(R/R) mice and littermates. We found 56 editing sites with significantly diminished editing levels in Adar2 deficient animals with the majority in coding regions. Only two genes and 3 exons showed statistically significant differences in expression levels. This work illustrates that ADAR2 is important in site-specific changes of protein coding sequences but has relatively modest effects on gene expression and splicing in the adult mouse frontal cortex. PMID- 26669817 TI - Sulfur and Nitrogen Co-Doped Graphene Electrodes for High-Performance Ionic Artificial Muscles. AB - Sulfur and nitrogen co-doped graphene electrodes for bioinspired ionic artificial muscles, which exhibit outstanding actuation performances (bending strain of 0.36%, 4.5 times higher than PEDOT: PSS electrodes, and 96% of initial strain after demonstration over 18 000 cycles), provide remarkable electro-chemo-mech anical properties: specific capacitance, electrical conductivity, and large surface area with mesoporosity. PMID- 26669818 TI - Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases. AB - As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. PMID- 26669819 TI - Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis. AB - Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection. PMID- 26669820 TI - Assessment of the efficacy of drug transdermal delivery by electro-phonophoresis in treating tuberculous lymphadenitis. AB - Electro-phonophoresis (EP) has been used in various clinical fields. The objective of present study is to evaluate the skin permeability of isoniazid (INH) and rifampicin (RIF) in patients with tuberculous lymphadenitis with the aid of EP to validate the clinical applications of this transdermal delivery system for the treatment of superficial extrapulmonary tuberculosis. INH and RIF solutions were delivered transdermally, with or without EP, in the surrounding tissue of the lesion for 0.5 h. Local pyogenic fluids or necrotic tissue samples from the infection sites in patients were collected at 1 h after dosing. Drug concentrations in samples were evaluated by high performance liquid chromatography. The median INH and RIF intra-lesional concentrations were 0.365 (interquartile range [IQR] 0.185-1.775) MUg/mL and 1.231 (IQR 0.304-1.836) MUg/mL in oral group; 2.964 (IQR 0.193-7.325) MUg/mL and 2.646 (IQR 1.211-3.753) MUg/mL in INH- and RIF-transdermal plus EP group. Drug concentrations in the local sites of patients receiving INH or RIF through EP transdermal delivery were statistically higher than those observed in patients only taking INH and RIF orally. However, this enhancement was not observed in the transdermal delivery of INH or RIF without EP in contrast to the oral administrations of drugs. EP can effectively enhance the skin permeability of INH and RIF in patients with tuberculous lymphadenitis. The increase in drug concentrations in the lesions could help eradication of the germs; shorten the treatment course and increase the cure rate of patients with tuberculous lymphadenitis. PMID- 26669821 TI - Effectiveness of team training in managing shoulder dystocia: a retrospective study. AB - OBJECTIVES: To evaluate the effectiveness of simulation team training for the management of shoulder dystocia. Primary outcome measures were the number of reported cases of shoulder dystocia, as well as fetal injury that occurred from it. Secondary outcome is documentation of manoeuvres used to alleviate shoulder dystocia. METHODS: Retrospective cohort study in a teaching hospital in the Netherlands, in a 38 month period before and after implementation of team training. RESULTS: We compared 3492 term vaginal cephalic deliveries with 3496 deliveries before and after team training. Incidence of shoulder dystocia increased from 51 to 90 cases (RR 1.8 (95% CI: 1.3-2.5)). Fetal injury occurred in 16 and eight cases, respectively (RR 0.50 (95% CI: 0.21-1.2)). Before team training started, the all-fours manoeuvre was never used, while after team training it was used in 41 of 90 cases (45%). Proper documentation of all manoeuvres used to alleviate shoulder dystocia significantly increased after team training (RR 1.6 (95% CI: 1.05-2.5)). CONCLUSIONS: Simulation team training increased the frequency of shoulder dystocia, facilitated implementation of the all-fours technique, improved documentation of delivery notes and may have a beneficial effect on the number of children injured due to shoulder dystocia. PMID- 26669822 TI - Effect of postoperative use of diclofenac on pharyngocutaneous fistula development after primary total laryngopharyngectomy: Results of a single-center retrospective study. AB - BACKGROUND: Primary total laryngopharyngectomy is the treatment of choice in many cases of locally advanced hypopharyngeal and laryngeal cancer. Development of pharyngocutaneous fistulae is the most common postoperative complication. A recent Danish study showed significantly increased rates of anastomosal leakage after colorectal resection in patients receiving diclofenac treatment. METHODS: We retrospectively analyzed 67 patients after primary total laryngopharyngectomy to determine whether diclofenac increases the risk for development of pharyngocutaneous fistula analogously to leakage in the colorectal area. RESULTS: The fistula rate in the total study population (n = 67) was 19.4%. In the group receiving diclofenac postoperatively (n = 31), the fistula rate was 25.8%. In the patient group not receiving diclofenac (n = 36), the fistula rate was 13.9% (p = .219). CONCLUSION: Our results suggest that cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) should be administered with caution after laryngopharyngectomy. Additional studies on larger cohorts are required to further evaluate our findings. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1515-E1520, 2016. PMID- 26669823 TI - The urticating setae of Ochrogaster lunifer, an Australian processionary caterpillar of veterinary importance. AB - The bag-shelter moth, Ochrogaster lunifer Herrich-Schaffer (Lepidoptera: Notodontidae), is associated with a condition called equine amnionitis and fetal loss (EAFL) on horse farms in Australia. Setal fragments from O. lunifer larvae have been identified in the placentas of experimentally aborted fetuses and their dams, and in clinical abortions. The gregarious larvae build silken nests in which large numbers cohabit over spring, summer and autumn. The final instars disperse to pupation sites in the ground where they overwinter. Field-collected O. lunifer larvae, their nests and nearby soil were examined using light and electron microscopy to identify setae likely to cause EAFL and to determine where and how many were present. Microtrichia, barbed hairs and true setae were found on the exoskeletons of the larvae. True setae matching the majority of setal fragments described from equine tissue were found on third to eighth instar larvae or exuviae. The number of true setae increased with the age of the larva; eighth instars carried around 2.0-2.5 million true setae. The exuvia of the pre pupal instar was incorporated into the pupal chamber. The major sources of setae are likely to be nests, dispersing pre-pupal larvae and their exuviae, and pupal chambers. PMID- 26669825 TI - Efficient Use of an Adapting Database of Ab Initio Calculations To Generate Accurate Newtonian Dynamics. AB - We develop and demonstrate a method to efficiently use density functional calculations to drive classical dynamics of complex atomic and molecular systems. The method has the potential to scale to systems and time scales unreachable with current ab initio molecular dynamics schemes. It relies on an adapting dataset of independently computed Hellmann-Feynman forces for atomic configurations endowed with a distance metric. The metric on configurations enables fast database lookup and robust interpolation of the stored forces. We discuss mechanisms for the database to adapt to the needs of the evolving dynamics, while maintaining accuracy, and other extensions of the basic algorithm. PMID- 26669824 TI - Effects of anaesthesia on proliferation, invasion and apoptosis of LoVo colon cancer cells in vitro. AB - Tumour cell proliferation, invasion and apoptosis are crucial steps in tumour metastasis. We evaluated the effect of serum from patients undergoing colon cancer surgery receiving thoracic epidural and propofol anaesthesia on colon cancer cell biology. Patients were randomly assigned to receive propofol anaesthesia with a concomitant thoracic epidural (PEA, n = 20) or sevoflurane anaesthesia with opioid analgesia (SGA, n = 20). Venous blood was obtained before induction of anaesthesia and 24 hours postoperatively. The LoVo colon cancer cells were cultured with patient serum from both groups and the effects on proliferation, invasion and apoptosis were measured. Twenty-four hours after surgery, the absorbance value of LoVo cells at 10% serum concentration from PEA was decreased when compared with SGA (0.302 (0.026) vs 0.391 (0.066), p = 0.005). The inhibitory rate of LoVo cells at 10% serum concentration from PEA was higher than that from SGA (p = 0.004) 24 h after surgery. The number of invasive LoVo cells at 10% serum concentration from PEA was reduced when compared with SGA (44 (4) vs 62 (4), p < 0.001). Exposure of LoVo cells to postoperative serum from patients receiving PEA led to a higher luminescence ratio (apoptosis) than those receiving SGA (0.36 (0.04) vs 0.27 (0.05), p < 0.001). Serum from patients receiving PEA for colon cancer surgery inhibited proliferation and invasion of LoVo cells and induced apoptosis in vitro more than that from patients receiving SGA. Anaesthetic technique might influence the serum milieu in a way that affects cancer cell biology and, thereby, tumour metastastasis. PMID- 26669826 TI - Optical Anisotropy of Black Phosphorus in the Visible Regime. AB - The striking in-plane anisotropy remains one of the most intriguing properties for the newly rediscovered black phosphorus (BP) 2D crystals. However, because of its rather low-energy band gap, the optical anisotropy of few-layer BP has been primarily investigated in the near-infrared (NIR) regime. Moreover, the essential physics that determine the intrinsic anisotropic optical property of few-layer BP, which is of great importance for practical applications in optical and optoelectronic devices, are still in the fancy of theory. Herein, we report the direct observation of the optical anisotropy of few-layer BP in the visible regime simply by using polarized optical microscopy. On the basis of the Fresnel equation, the intrinsic anisotropic complex refractive indices (n-ikappa) in the visible regime (480-650 nm) were experimentally obtained for the first time using the anisotropic optical contrast spectra. Our findings not only provide a convenient approach to measure the optical constants of 2D layered materials but also suggest a possibility to design novel BP-based photonic devices such as atom thick light modulators, including linear polarizer, phase plate, and optical compensator in a broad spectral range extending to the visible window. PMID- 26669828 TI - Birth registration and child undernutrition in sub-Saharan Africa. AB - OBJECTIVE: In many countries of the world millions of people are not registered at birth. However, in order to assess children's nutritional status it is necessary to have an exact knowledge of their age. In the present paper we discuss the effects of insufficient or imprecise age data on estimates of undernutrition prevalence. DESIGN: Birth registration rates and levels of stunting, underweight and wasting were retrieved from Multiple Indicator Cluster Surveys and Demographic and Health Surveys of thirty-seven sub-Saharan African countries, considering the subdivision in wealth quintiles. The composition of the cross-sectional sample used for nutritional evaluation was analysed using a permutation test. Logistic regression was applied to analyse the relationship between birth registration and undernutrition. The 95 % probability intervals and Student's t test were used to evaluate the effect of age bias and error. RESULTS: Heterogeneous sampling designs were detected among countries, with different percentages of children selected for anthropometry. Further, registered children were slightly more represented within samples used for nutritional analysis than in the total sample. A negative relationship between birth registration and undernutrition was recognized, with registered children showing a better nutritional status than unregistered ones, even within each wealth quintile. The over- or underestimation of undernutrition in the case of systematic over- or underestimation of age, respectively, the latter being more probable, was quantified up to 28 %. Age imprecision was shown to slightly overestimate undernutrition. CONCLUSIONS: Selection bias towards registered children and underestimation of children's age can lead to an underestimation of the prevalence of undernutrition. PMID- 26669827 TI - Lung Deposition of Alpha1-Proteinase Inhibitor (Human) (A1-PI[H]) Inhalation Solution Using Two Inhalation Modes of the I-neb Adaptive Aerosol Delivery (AAD) System in Healthy Subjects and Subjects with Cystic Fibrosis. AB - BACKGROUND: In cystic fibrosis (CF) patients, inhalation of alpha1-proteinase inhibitor (A1-PI) can prevent or slow down persistent infections and reduce the massive ongoing inflammation and excessive levels of NE that destroy the airway epithelium, leading to progressive loss of pulmonary function and death. It is essential for an efficient treatment with inhaled A1-PI that an adequate and reproducible dose is deposited within all regions of the lung. The I-neb AAD System provides two inhalation modes: the Target Inhalation Mode (TIM) and the Tidal Breathing Mode (TBM). Both were compared in this study for their efficiency to deliver A1-PI to the lungs. METHODS: This was a randomized, open label, cross over study to investigate the lung deposition of A1-PI in 6 healthy subjects (HS) and 15 CF subjects. The primary endpoint was to evaluate the total lung deposition relative to filling dose of A1-PI inhalation solution using the I-neb AAD System in TIM and in TBM. The main secondary endpoints were extra-thoracic deposition, exhaled drug fraction, nebulizer residue, C/P ratio, and variance of pixel counts. Additional exploratory endpoints were total treatment time and the inhalation time. Radiolabeling was performed considering GMP using a commercially available sterile labeling kit. Radiolabeling was validated using NGI data acquired by gamma scintillation and UV spectrometry. RESULTS AND CONCLUSIONS: The intrapulmonary deposition (mean +/- SD) in CF subjects was 47.0% +/- 6.6% and 46.7% +/- 10.3% in TIM and TBM, respectively, and in healthy subjects, 50.0% +/- 6.7% and 54.8% +/- 7.0% in TIM and TBM, respectively. TIM resulted in an approximately 40% lower treatment time (HS 6.4 min vs. 10.3 min, CF 5.3 min vs. 10.7 min) and less extra-thoracic deposition compared to TBM, and showed a higher residue of drug in the nebulizer, compared to TBM. In both groups, inhalation of a single dose of 77 mg of A1-PI was efficient, safe, and well tolerated using TIM and TBM. PMID- 26669829 TI - Primary tumour characteristics predict the invasiveness of lymph node metastases in papillary thyroid carcinoma patients. AB - OBJECTIVE: This study evaluated whether primary tumour characteristics are associated with specific features of metastatic lymph nodes in papillary thyroid carcinoma patients. METHOD: A retrospective review of 411 patients with pathologically diagnosed cervical lymph node metastasis was conducted. RESULTS: A metastatic lymph node focus size of at least 2 mm was independently associated with a primary tumour size of at least 1 cm (hazard ratio 1.962) and with male sex (hazard ratio 1.947). A number of at least five lymph node metastases was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.863), extrathyroidal extension (hazard ratio 1.737) and male sex (hazard ratio 1.689). Extranodal extension was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.288), extrathyroidal extension (2.201) and male sex (hazard ratio 1.733). CONCLUSION: Primary papillary thyroid carcinoma characteristics are related to the pathological features of lymph node metastases. PMID- 26669831 TI - ASAPS Presidents Reflect on the Aesthetic Surgery Journal's 20 Years of Success. PMID- 26669832 TI - 20th Anniversary Interview With ASJ Editor-in-Chief Dr Foad Nahai. PMID- 26669833 TI - Nigersaurus Revisited. PMID- 26669834 TI - ASJ: Fulfilling the Promise. PMID- 26669835 TI - Landfilling and landfill mining. PMID- 26669837 TI - POSTERIOR VITREOUS DETACHMENT IN HIGHLY MYOPIC EYES UNDERGOING VITRECTOMY. AB - PURPOSE: To assess the rate of complete posterior vitreous detachment (PVD) in highly myopic eyes requiring vitreoretinal surgery based on intraoperative observations. METHODS: Monocentric retrospective observational case series of consecutive highly myopic patients whose eyes underwent 25 G 3-port pars plana vitrectomy between 2009 and 2012. Patients were operated on for rhegmatogenous retinal detachment, epiretinal membrane, macular hole with retinal detachment, myopic foveoschisis, and myopic macular hole. Patient records were reviewed focusing on the intraoperative assessment of PVD which was assisted in most cases by a visualization agent. RESULTS: Ninety-six eyes of 95 patients whose mean age was 62.15 +/- 12.4 years (29-95) were included. Complete PVD was observed in 52.1% of eyes. The PVD rate varied depending on the disease (P < 0.0001). It was high in retinal detachment and epiretinal membrane (85 and 74.2%, respectively) and low in myopic foveoschisis and myopic macular hole (14.3 and 10%, respectively). Complete PVD was found in 42.9% of macular hole with retinal detachment. CONCLUSION: In highly myopic eyes, the rate of complete PVD varied widely depending on the vitreoretinal disease operated on. The posterior vitreous cortex was often detached from the retina in retinal detachment and epiretinal membrane but was most often attached in myopic foveoschisis and macular hole. PMID- 26669838 TI - The Intraoperative Effect of Methadone on Somatosensory Evoked Potentials. AB - BACKGROUND: Evoked potentials (EP), both somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP), are often used during complex spine surgery to monitor the integrity of spinal pathways during operations in or around the spine. Changes in these monitored EP signals (increased latency and decreased amplitude) may result from ischemia, direct surgical injury, changes in blood pressure, hypoxia, changes in CO2 tension, and anesthetic agents. Typically, a clinically significant change for SSEPs is defined as an increase in latency >10% or a decrease of amplitude >50%. A clinically significant change for TcMEPs is much more complex but is also described in terms of large signal loss or decrease. Opioids have been shown to both increase latency and decrease the amplitude of SSEPs, although this change is usually not clinically significant. There has been a renewed interest in methadone for use in spine and other complex surgeries. However, the effect of methadone on intraoperative monitoring of SSEPs and TcMEPs is unknown. We present the first study to directly look at the effects of methadone on SSEP and TcMEP monitoring during complex spine surgery. METHODS: The goal of this study was to observe the effect of methadone on an unrandomized set of patients. The primary endpoint was methadone's effect on SSEPs, and the secondary endpoint was methadone's effect on TcMEPs. Adult patients undergoing spine surgery requiring intraoperative neuromonitoring were induced with general anesthesia and had a baseline set of SSEPs and TcMEPs recorded. Next, methadone dosed 0.2 mg/kg/lean body weight was given. Repeat SSEPs and TcMEPs were recorded at 5, 10, and 15 minutes, with the timing based on distribution half-life of methadone between 6 and 8 minutes. Postoperatively, adverse events from methadone administration were collected. RESULTS: There was a statistically significant difference found in SSEPs for N20 latency (95% confidence interval [CI], 0.17 0.53; P=0.028), P37 latency (95% CI, 0.65-1.25; P=0.001), and N20 amplitude (95% CI, 0.09-0.32; P=<0.001), but not for P37 amplitude (95% CI, -0.19 to 0.00; P=0.634). There was no significant effect found for TcMEPs, the secondary endpoint of the study, and there were minimal adverse events recorded postoperatively. CONCLUSIONS: The data demonstrate that a single intravenous dose of methadone has a statistically significant difference on the amplitude and latency of SSEPs. However, this statistical difference does not translate into a clinical significance. PMID- 26669836 TI - The Antimicrobial Properties of Silver Nanoparticles in Bacillus subtilis Are Mediated by Released Ag+ Ions. AB - The superior antimicrobial properties of silver nanoparticles (Ag NPs) are well documented, but the exact mechanisms underlying Ag-NP microbial toxicity remain the subject of intense debate. Here, we show that Ag-NP concentrations as low as 10 ppm exert significant toxicity against Bacillus subtilis, a beneficial bacterium ubiquitous in the soil. Growth arrest and chromosomal DNA degradation were observed, and flow cytometric quantification of propidium iodide (PI) staining also revealed that Ag-NP concentrations of 25 ppm and above increased membrane permeability. RedoxSensor content analysis and Phag-GFP expression analysis further indicated that reductase activity and cytosolic protein expression decreased in B. subtilis cells treated with 10-50 ppm of Ag NPs. We conducted X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses to directly clarify the valence and fine structure of Ag atoms in B. subtilis cells placed in contact with Ag NPs. The results confirmed the Ag species in Ag NP-treated B. subtilis cells as Ag2O, indicating that Ag-NP toxicity is likely mediated by released Ag+ ions from Ag NPs, which penetrate bacterial cells and are subsequently oxidized intracellularly to Ag2O. These findings provide conclusive evidence for the role of Ag+ ions in Ag-NP microbial toxicity, and suggest that the impact of inappropriately disposed Ag NPs to soil and water ecosystems may warrant further investigation. PMID- 26669839 TI - Intraoperative Seizures Presenting as Refractory Hypotension. PMID- 26669840 TI - Acute Pulmonary Edema Following Plasma Exchange in a Patient With Guillian Barre Syndrome. PMID- 26669841 TI - Prevalence and Positive Correlates of Posttraumatic Stress Disorder Symptoms among Chinese Patients with Hematological Malignancies: A Cross-Sectional Study. AB - PURPOSE: Positive psychological constructs have been given increasing attention in research on the coping resources of cancer-related distresses. However, little research is available on posttraumatic stress disorder (PTSD) in patients with hematological malignancies. The purposes of this study were to assess the prevalence of PTSD symptoms and to explore the associations of perceived social support (PSS), hope, optimism and resilience with PTSD symptoms among Chinese patients with hematological malignancies. METHODS: A cross-sectional study was conducted during the period from July 2013 through April 2014. A total of 225 inpatients with hematological malignancies, which were eligible for the study, completed the Post-traumatic Stress Checklist-Civilian Version, Multidimensional Scale of Perceived Social Support, Adult Hope Scale, Life Orientation Scale Revised, and Resilience Scale. Hierarchical regression analysis was performed to explore the correlates of PTSD symptoms. RESULTS: Overall, the prevalence of PTSD symptoms was 10.7%. Initially, PSS was negatively associated with PTSD symptoms (beta = -0.248, P < 0.01). However, when positive psychological variables were added, optimism was negatively associated with PTSD symptoms (beta = -0.452, P < 0.01), and gender had a significant effect on PTSD symptoms. Women were more vulnerable to these symptoms than men (beta = 0.123, P < 0.05). When the analysis was performed separately by gender, only optimism showed a significantly negative association with PTSD symptoms in both men (beta = -0.389, P < 0.01) and women (beta = -0.493, P < 0.01). CONCLUSIONS: Some patients with hematological malignancies suffer from PTSD symptoms. The positive effects of PSS and optimism on PTSD symptoms suggest that an integrated approach to psychosocial intervention from both external and internal perspectives could have practical significance. Gender difference should be considered in developing potential interventions in reducing cancer-related PTSD symptoms. PMID- 26669842 TI - 3D printed nervous system on a chip. AB - Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology. PMID- 26669843 TI - Fibromyalgia Syndrome: Current Considerations in Symptom Management. AB - Fibromyalgia syndrome (FMS), one of the most common rheumatic disorders, is estimated to affect up to 15 million people in the United States, 80% to 90% of whom are women. The syndrome is characterized by the presence of chronic widespread pain and various concurrent symptoms, which may include fatigue, cognitive disturbances (memory problems, difficulty concentrating, confusion), distressed mood (anxiety, depression), nonrestorative sleep, and muscular stiffness. Symptom management appears to be best addressed using a multimodal approach, with treatment strategies tailored to the individual. While medication may provide adequate symptom relief for some patients, experts generally recommend integrating both pharmacologic and nonpharmacologic approaches. Some patients may benefit from the adjunctive use of complementary and alternative medicine (CAM) modalities. Because symptom remission is rare and medication adverse effects can complicate symptom management, well-informed nursing care practices and patient education are essential. This article describes the existing treatment guidelines, discusses pharmacologic and nonpharmacologic approaches (including CAM-based modalities), and outlines nursing approaches aimed at enhancing patient self-management. PMID- 26669844 TI - Many Benefits, Little Risk: The Use of Massage in Nursing Practice. AB - Since ancient times, massage therapy has been used to promote healing by people of all backgrounds and cultures. Massage therapy was once taught as a core nursing skill, but it gradually lost ground in the United States during the second half of the 20th century with the increased use of technology and documentation in nursing. In recent years, however, there has been a resurgence in the use of massage therapy. Research has provided insight into the mechanisms by which massage supports the healing process, and this has sparked support for including massage therapy in routine hospital care. In this article, the authors touch on the history of massage in nursing care and discuss its emotional and physiologic benefits for both patient and nurse. They describe specific massage techniques and discuss precautions to consider before using massage with certain patients. PMID- 26669845 TI - Catalytic reductive N-alkylation of amines using carboxylic acids. AB - We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction. PMID- 26669846 TI - Perspectives. PMID- 26669847 TI - Feasibility of US-CT image fusion to identify the sources of abnormal vascularization in posterior sacroiliac joints of ankylosing spondylitis patients. AB - Ultrasound (US) can be used to evaluate the inflammatory activity of the sacroiliac joints (SIJs) in ankylosing spondylitis (AS) patients, but to precisely locate the abnormal vascularization observed on color Doppler US (CDUS) was difficult. To address this issue, we performed US and computed tomography (CT) fusion imaging of SIJs with 84 inpatients and 30 controls, and then assessed the sources of abnormal vascularization in the posterior SIJs of AS patients based on the fused images. Several possible factors impacting the fusion process were considered including the lesion classes of SIJ, the skinfold thickness of the sacral region and the cross-sectional levels of the first, second and third posterior sacral foramina. Our data showed high image fusion success rates at the 3 levels in the AS group (97.0%, 87.5% and 79.8%, respectively) and the control group (96.7%, 86.7%, and 86.7%, respectively).The skinfold thickness was identified as the main factor affecting the success rates. The successfully fused images revealed significant differences in the distribution of abnormal vascularization between 3 levels, as detected via CDUS (P = 0.011), which suggested that inflammation occurred in distinct tissues at different levels of the SIJ (intraligamentous inflammation in Regions 1 and 2; intracapsular inflammation in Region 3). PMID- 26669848 TI - Urinary metabolites of 1-nitropyrene in US-Mexico border residents who frequently cross the San Ysidro Port of Entry. AB - Diesel exhaust presents a community exposure hazard, but methods to measure internal exposure are lacking. We report results from a community-based study using 1-nitropyrene (1-NP) and its urinary metabolites as markers of exposure to traffic-related diesel particulate matter (DPM). The study participants were Tijuana, Mexico residents who commuted on foot into San Diego, California for work or school using the International San Ysidro Port of Entry, placing them within feet of idling traffic (referred to as border commuters). The comparison group (non-border commuters) was comprised of residents of south San Diego who did not commute into Mexico. Air concentration of 1-NP in fine particulate matter (PM2.5) was measured in personal samples from participants. Spot urine samples were analyzed for 1-NP urinary metabolites 8-hydroxy-1-nitropyrene (8-OHNP) and 8 hydroxy-N-acetyl-1-aminopyrene (8-OHNAAP). Compared with non-border commuters, border commuters had two- to threefold higher mean urinary concentrations for unadjusted and creatinine-adjusted 8-OHNP and 8-OHNAAP. Urinary 8-OHNAAP and the sum of 8-OHNP and 8-OHNAAP were both associated with personal exposure to 1-NP in the prior 24 h. These results suggest that 1-NP urinary metabolites reflect recent exposure to DPM-derived 1-NP in community settings and can be useful for exposure analysis. PMID- 26669849 TI - Analysis of personal and bedroom exposure to ELF-MFs in children in Italy and Switzerland. AB - Little is known about the real everyday exposure of children in Europe to extremely low-frequency magnetic fields (ELF-MFs). The aims of this study are to (i) assess personal ELF-MF exposure in children; (ii) to identify factors determining personal and bedroom ELF-MF exposure measurements in children; (iii) to evaluate the reproducibility of exposure summary measures; and (iv) to compare personal with bedroom measurements. In Switzerland and Italy, 172 children aged between 5 and 13 years were equipped with ELF-MF measurement devices (EMDEX II, measuring 40-800 Hz) during 24-72 h twice, in the warm and the cold season. In addition, 24-h measurements were taken in the bedroom of children. In our study, sample geometric mean ELF-MF exposure was 0.04 MUT for personal and 0.05 MUT for bedroom measurements. Living within 100 m of a highest voltage power line increased geometric mean personal exposure by a factor of 3.3, and bedroom measurements by a factor 6.8 compared to a control group. Repeated measurements within the same subject showed high reproducibility for the geometric mean (Spearman's correlation 0.78 for personal and 0.86 for bedroom measurements) but less for the 95th and 99th percentile of the personal measurements (<=0.42). Spearman's correlation between bedroom and personal exposure was 0.86 for the geometric mean but considerably lower for the 95th and 99th percentiles (<=0.60). Most previous studies on ELF-MF childhood leukaemia used mean bedroom exposure. Our study demonstrates that geometric mean bedroom measurements is well correlated with personal geometric mean exposure, and has high temporal reproducibility. PMID- 26669851 TI - Does minimally invasive oesophagectomy provide a benefit in hospital length of stay when compared with open oesophagectomy? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: 'in patients undergoing oesophagectomy, does a minimally invasive approach convey a benefit in hospital length of stay (LOS), when compared to an open approach?' A total of 647 papers were identified, using an a priori defined search strategy; 24 papers represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and key results are tabulated. Of the studies identified, data from two randomized controlled trials were available. The first randomized study compared the use of open thoracotomy and laparotomy versus thoracoscopy and laparoscopy. Those undergoing minimally invasive oesophagectomy (MIO) left hospital on average 3 days earlier than those treated with the open oesophagectomy (OO) technique (P = 0.044). The other randomized trial, which compared thoracotomy with thoracoscopy and laparoscopy, demonstrated a reduction of 1.8 days in the LOS when employing the MIO technique (P < 0.001). With the addition of the remaining 22 non-randomized studies, comprising 3 prospective and 19 retrospective cohort studies, which are heterogeneous with regard to their design, study populations and outcomes; data are available representing 3173 MIO and 25 691 OO procedures. In total, 13 studies (including the randomized trials) demonstrate a significant reduction in hospital LOS associated with MIO; 10 suggest no significant difference between techniques; and only 1 suggests a significantly greater length of stay associated with MIO. The only two randomized trials comparing MIO and OO demonstrated a reduction in length of stay in the MIO group, without compromising survival or increasing complication rates. All bar one of the non-randomized studies demonstrated either a significant reduction in length of stay with MIO or no difference. The benefit in reduced length of stay was not at the cost of worsened survival or increased complications, and conversion rates in all studies were low. PMID- 26669850 TI - Inhalation cancer risk assessment of hexavalent chromium based on updated mortality for Painesville chromate production workers. AB - The exposure-response for hexavalent chromium (Cr(VI))-induced lung cancer among workers of the Painesville Ohio chromate production facility has been used internationally for quantitative risk assessment of environmental and occupational exposures to airborne Cr(VI). We updated the mortality of 714 Painesville workers (including 198 short-term workers) through December 2011, reconstructed exposures, and conducted exposure-response modeling using Poisson and Cox regressions to provide quantitative lung cancer risk estimates. The average length of follow-up was 34.4 years with 24,535 person-years at risk. Lung cancer was significantly increased for the cohort (standardized mortality ratio (SMR)=186; 95% confidence interval (CI) 145-228), for those hired before 1959, those with >30-year tenure, and those with cumulative exposure >1.41 mg/m(3) years or highest monthly exposures >0.26 mg/m(3). Of the models assessed, the linear Cox model with unlagged cumulative exposure provided the best fit and was preferred. Smoking and age at hire were also significant predictors of lung cancer mortality. Adjusting for these variables, the occupational unit risk was 0.00166 (95% CI 0.000713-0.00349), and the environmental unit risk was 0.00832 (95% CI 0.00359-0.0174), which are 20% and 15% lower, respectively, than values developed in a previous study of this cohort. PMID- 26669852 TI - Reusing the patent internal mammary artery as a conduit in redo coronary artery bypass surgery. AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, in patients with previous internal mammary artery/internal thoracic artery (ITA) grafts, can the internal mammary artery/ITA be reused/recycled in redo coronary artery bypass surgery? Fourteen papers were found using the reported search of which 10 represented the best evidence to answer the clinical question. There was variation in patient selection, the number of patients reported, outcome measures recorded, and methods and duration of follow-up. The results were mostly in favour of using a recycled ITA when it could be safely harvested. Most studies were retrospective. One large series of 60 patients who underwent redo coronary artery bypass grafting (CABG) using previously implanted ITAs had a mean time to reoperation of 117 +/- 68 months. They reported no operative deaths; no patients required further or subsequent target vessel revascularization; 30-day mortality was 8.3% and myocardial infarction rate was 3%. Another two series of 16 and 12 patients underwent recycling of arterial grafts during coronary artery revascularization with no perioperative deaths in either. Postoperative angiography was performed in 10 patients in one of these studies, which showed excellent flow in all redone left internal thoracic artery (LITA) grafts. One study reported results from a prospective cohort of 9 patients who underwent redo coronary artery bypass grafting. Interval between operations was between 1 and 132 months. There was no perioperative mortality, but 1 patient required reintervention (to an interposition vein graft). A further study of 4 patients who underwent redo CABG using ITAs that were patent but with severe stenosis at the distal anastomosis had no mortality. Postoperative angiography showed patency of all grafts. There have also been 4 case reports on reusing the ITA/ITA in redo CABG with no damage to the reused LITA, no perioperative mortality and satisfactory follow-up at up to 29 months. Evidently, the recycled ITA can be used in redo coronary artery bypass grafting. Papers found were retrospective series or case reports. As such, there is no direct comparison in outcomes between the recycled ITA and first-time ITA harvest or any other conduit for CABG. In conclusion, we find that when it is possible to harvest a previously used ITA, studies have shown it to be a safe and viable conduit in redo CABG with good long-term outcomes. PMID- 26669853 TI - Delayed recovery of right ventricular systolic function after repair of long standing tricuspid regurgitation associated with severe right ventricular failure. AB - After tricuspid valve surgery for long-standing tricuspid regurgitation associated with right ventricular failure, reverse remodelling of the enlarged right ventricle, including recovery of right ventricular systolic function, is unpredictable. We present the case of a 31-year old man with early reduction of dilated right ventricular dimensions and delayed recovery of impaired right ventricular systolic function after valve repair for traumatic tricuspid regurgitation lasting 16 years. PMID- 26669854 TI - A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 beta-N-acetylglucosaminidase. AB - Glycoside hydrolase (GH) family 3 beta-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 beta-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 A resolution. The three dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions--a GH family 3 beta-N acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain beta-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID- 26669855 TI - TALENs-mediated gene disruption of FLT3 in leukemia cells: Using genome-editing approach for exploring the molecular basis of gene abnormality. AB - Novel analytic tools are needed to elucidate the molecular basis of leukemia relevant gene mutations in the post-genome era. We generated isogenic leukemia cell clones in which the FLT3 gene was disrupted in a single allele using TALENs. Isogenic clones with mono-allelic disrupted FLT3 were compared to an isogenic wild-type control clone and parental leukemia cells for transcriptional expression, downstream FLT3 signaling and proliferation capacity. The global gene expression profiles of mutant K562 clones and corresponding wild-type controls were compared using RNA-seq. The transcriptional levels and the ligand-dependent autophosphorylation of FLT3 were decreased in the mutant clones. TALENs-mediated FLT3 haplo-insufficiency impaired cell proliferation and colony formation in vitro. These inhibitory effects were maintained in vivo, improving the survival of NOD/SCID mice transplanted with mutant K562 clones. Cluster analysis revealed that the gene expression pattern of isogenic clones was determined by the FLT3 mutant status rather than the deviation among individual isogenic clones. Differentially expressed genes between the mutant and wild-type clones revealed an activation of nonsense-mediated decay pathway in mutant K562 clones as well as an inhibited FLT3 signaling. Our data support that this genome-editing approach is a robust and generally applicable platform to explore the molecular bases of gene mutations. PMID- 26669856 TI - Nontypeable Haemophilus influenzae-Induced MyD88 Short Expression Is Regulated by Positive IKKbeta and CREB Pathways and Negative ERK1/2 Pathway. AB - Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by excessive inflammation and are exacerbated by nontypeable Haemophilus influenzae (NTHi). Airway epithelial cells mount the initial innate immune responses to invading pathogens and thus modulate inflammation. While inflammation is necessary to eliminate a pathogen, excessive inflammation can cause damage to the host tissue. Therefore, the inflammatory response must be tightly regulated and deciphering the signaling pathways involved in this response will enhance our understanding of the regulation of the host inflammatory response. NTHi binds to TLR2 and signal propagation requires the adaptor molecule myeloid differentiation factor 88 (MyD88). An alternative spliced form of MyD88 is called MyD88 short (MyD88s) and has been identified in macrophages and embryonic cell lines as a negative regulator of inflammation. However, the role of MyD88s in NTHi-induced inflammation in airway epithelial cells remains unknown. Here we show that NTHi induces MyD88s expression and MyD88s is a negative regulator of inflammation in airway epithelial cells. We further demonstrate that MyD88s is positively regulated by IKKbeta and CREB and negatively regulated by ERK1/2 signaling pathways. Taken together these data indicate that airway inflammation is controlled in a negative feedback manner involving MyD88s and suggest that airway epithelial cells are essential to maintain immune homeostasis. PMID- 26669857 TI - Counselling practices in community pharmacies in Riyadh, Saudi Arabia: a cross sectional study. AB - BACKGROUND: Community pharmacists play a crucial role in optimising medication use and improving patient outcomes, whilst preventing medication misuse and reducing costs. Evidence suggests that pharmacists counselling improves clinical outcomes, quality of life, drug and disease knowledge and reduces health service utilisation. This study aims to investigate the counselling practices of community pharmacists in Riyadh, the capital of Saudi Arabia. METHODS: The study consisted of two parts: simulated patients (SPs) visits to observe actual counselling practices, and a cross-sectional survey of community pharmacists to assess their reported counselling practices. In the SPs method, there were four scenarios involving four medications. Scenarios 1 and 2 concerned drug-drug interactions, scenario 3 concerned the proper time of administration, and scenario 4 concerned side effects. The simulated visits were conducted between April and May 2012. A four-sections questionnaire was distributed in the same period. RESULTS: We conducted 161 simulated visits. Out of the 161 visits a medicine was dispensed in 150 visits. When SPs requested medications, pharmacists asked questions during 15 visits (10.0%), provided information during 7 visits (4.6%), and both asked questions and provided information, i.e. provided counselling, during 4 visits (2.6%). When the SPs started to be inquisitive and demanded information, pharmacists asked SPs questions during 71 visits (47.3%), provided information during 150 visits (100%), and both asked questions and provided information, i.e. provided counselling, during 65 visits (43.3%). Information regarding dose was the most common type of information provided in 146 visits (97.3%). After the SPs started to be inquisitive and probed for information, only 10% were counselled on precautions. In the cross-sectional survey, four hundred pharmacists were approached and 350 agreed to participate in the questionnaire (87% response rate). Of the respondents, 223 (63.7%) reported that they usually or always tell the patient about the purpose of medicines or the diagnosis, 302 (86.2%) reported that they usually or always give patient information on how to use or apply the medicine; 299 (85.3%) said they were satisfied with their counselling practices. CONCLUSIONS: The present study highlights the current deficiencies in appropriate dispensing practices and medication counselling at community pharmacies in Saudi Arabia. Policy makers, stakeholders, and researchers should collaborate to design interventions to improve the current dispensing practices at community pharmacies across the country. PMID- 26669858 TI - The global landscape of cognition: hierarchical aggregation as an organizational principle of human cortical networks and functions. AB - Though widely hypothesized, limited evidence exists that human brain functions organize in global gradients of abstraction starting from sensory cortical inputs. Hierarchical representation is accepted in computational networks, and tentatively in visual neuroscience, yet no direct holistic demonstrations exist in vivo. Our methods developed network models enriched with tiered directionality, by including input locations, a critical feature for localizing representation in networks generally. Grouped primary sensory cortices defined network inputs, displaying global connectivity to fused inputs. Depth-oriented networks guided analyses of fMRI databases (~17,000 experiments;~1/4 of fMRI literature). Formally, we tested whether network depth predicted localization of abstract versus concrete behaviors over the whole set of studied brain regions. For our results, new cortical graph metrics, termed network-depth, ranked all databased cognitive function activations by network-depth. Thus, we objectively sorted stratified landscapes of cognition, starting from grouped sensory inputs in parallel, progressing deeper into cortex. This exposed escalating amalgamation of function or abstraction with increasing network-depth, globally. Nearly 500 new participants confirmed our results. In conclusion, data-driven analyses defined a hierarchically ordered connectome, revealing a related continuum of cognitive function. Progressive functional abstraction over network depth may be a fundamental feature of brains, and is observed in artificial networks. PMID- 26669859 TI - Femoral nerve block-sciatic nerve block vs. femoral nerve block-local infiltration analgesia for total knee arthroplasty: a randomized controlled trial. AB - BACKGROUND: The use of femoral nerve block (FNB) combined with sciatic nerve block (SNB) after total knee arthroplasty (TKA) has recently become controversial. Local infiltration analgesia (LIA) has been reported to be effective for postoperative TKA pain control. We aimed to assess whether LIA with continuous FNB is as effective as SNB combined with continuous FNB. METHODS: This was a prospective, randomized, single-center, observer-blinded, parallel group comparison trial of 34 American Society of Anesthesiologists (ASA) physical status 1-3 patients who underwent TKA and fulfilled the inclusion and exclusion criteria. Patients were randomized into two groups: a periarticular LIA and FNB group (group L, n = 17), and an SNB and FNB group (group S, n = 17). In both groups, participants received FNB with 20 mL of 0.375% ropivacaine, and 5 mL h( 1) of 0.2% ropivacaine after surgery. In group L, participants received 100-ml injections of 0.2% ropivacaine and 0.5 mg epinephrine to the surgical region. In group S, participants received SNB with 20 ml of 0.375% ropivacaine. After TKA, Numeric Rating Scale (NRS) scores for the first 24 h post-operation were compared via repeated-measures analysis of variance (ANOVA) as the primary outcome. Other outcome measures included NRS score changes within groups, area under the curve for the NRS scores, total analgesic dose, change in knee flexion and extension, pain control satisfaction, nausea and vomiting, and hospital stay duration. RESULTS: NRS score changes were greater in group L than in group S (P < 0.01, ANOVA) and greater in group L than in group S at three postoperative time points: 3 h (P < 0.01), 6 h (P < 0.01), and 12 h (P = 0.013; Mann-Whitney U test). Changes in the mean NRS score were observed in each group (P < 0.01, Friedman test). No significant differences were detected in the other outcome measures (Mann-Whitney U, Wilcoxon signed-rank, and chi-squared tests). CONCLUSIONS: Sciatic nerve block with femoral nerve block is superior to local anesthetic infiltration with femoral nerve block for postoperative pain control within 3-12 h of total knee arthroplasty. TRIAL REGISTRATION: UMIN-CTR ID: 000013364 R: 000015591. PMID- 26669861 TI - spa Typing and Multilocus Sequence Typing Show Comparable Performance in a Macroepidemiologic Study of Staphylococcus aureus in the United States. AB - A number of molecular typing methods have been developed for characterization of Staphylococcus aureus isolates. The utility of these systems depends on the nature of the investigation for which they are used. We compared two commonly used methods of molecular typing, multilocus sequence typing (MLST) (and its clustering algorithm, Based Upon Related Sequence Type [BURST]) with the staphylococcal protein A (spa) typing (and its clustering algorithm, Based Upon Repeat Pattern [BURP]), to assess the utility of these methods for macroepidemiology and evolutionary studies of S. aureus in the United States. We typed a total of 366 clinical isolates of S. aureus by these methods and evaluated indices of diversity and concordance values. Our results show that, when combined with the BURP clustering algorithm to delineate clonal lineages, spa typing produces results that are highly comparable with those produced by MLST/BURST. Therefore, spa typing is appropriate for use in macroepidemiology and evolutionary studies and, given its lower implementation cost, this method appears to be more efficient. The findings are robust and are consistent across different settings, patient ages, and specimen sources. Our results also support a model in which the methicillin-resistant S. aureus (MRSA) population in the United States comprises two major lineages (USA300 and USA100), which each consist of closely related variants. PMID- 26669862 TI - It's Totally Tubular....Riding The New Wave of Ovarian Cancer Research. AB - Hereditary breast and ovarian cancer syndrome carries significant mortality for young women if effective preventive and screening measures are not taken. Preventive salpingo-oophorectomy is currently the only method known to reduce the risk of ovarian cancer-related death. Histopathological analyses of these surgical specimens indicate that a high proportion of ovarian cancers in women at high risk and in the general population arise from the fallopian tube. This paradigm shift concerning the cell of origin for the most common subtype of ovarian cancer, high-grade serous carcinoma, has sparked a major effort within the research community to develop new and robust model systems to study the fallopian tube epithelium as the cell of origin of "ovarian" cancer. In this review, evidence supporting the fallopian tube as the origin of ovarian cancer is presented as are novel experimental model systems for studying the fallopian tube epithelium in high-risk women as well as in the general population. This review also addresses the clinical implications of the newly proposed cell of origin, the clinical questions that arise, and novel strategies for ovarian cancer prevention. PMID- 26669863 TI - Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem like Cells with an Enhanced Proliferative Capacity. AB - The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression. PMID- 26669864 TI - Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL 3 Is Required for Potentiating Colorectal Oncogenesis. AB - Ubiquitin specific protease 4 (USP4) is a deubiquitinating enzyme with key roles in the regulation of p53 and TGFbeta signaling, suggesting its importance in tumorigenesis. However, the mechanisms and regulatory roles of USP4 in cancer, including colorectal cancer, remain largely elusive. Here, we present the first evidence that USP4 regulates the growth, invasion, and metastasis of colorectal cancer. USP4 expression was significantly elevated in colorectal cancer tissues and was significantly associated with tumor size, differentiation, distant metastasis, and poor survival. Knockdown of USP4 diminished colorectal cancer cell growth, colony formation, migration, and invasion in vitro and metastasis in vivo. Importantly, we found that phosphatase of regenerating liver-3 (PRL-3) is indispensable for USP4-mediated oncogenic activity in colorectal cancer. Mechanistically, we observed that USP4 interacted with and stabilized PRL-3 via deubiquitination. This resulted in activation of Akt and reduction of E-cadherin, critical regulators of cancer cell growth and metastasis. Examination of clinical samples confirmed that USP4 expression positively correlates with PRL-3 protein expression, but not mRNA transcript levels. Taken together, our results demonstrate that aberrant expression of USP4 contributes to the development and progression of colorectal cancer and reveal a critical mechanism underlying USP4 mediated oncogenic activity. These observations suggest that the potential of harnessing proteolytic degradation processes for therapeutic manipulation may offer a much-needed new approach for improving colorectal cancer treatment strategies. PMID- 26669865 TI - Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations. AB - Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are noninvasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy ((1)H-MRS) acquisition scheme that uses an ultrahigh magnetic field (>= 7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo (1)H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy. PMID- 26669866 TI - PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways. AB - Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumors and is generally strongly resistant to currently available chemo- and/or radiotherapy regimens, including targeted molecular therapies. Therefore, unraveling the molecular mechanisms underlying the aggressive behavior of pancreatic cancer is a necessary prerequisite for the development of novel therapeutic approaches. We previously identified the protein placenta-specific 8 (PLAC8, onzin) in a genome-wide search for target genes associated with pancreatic tumor progression and demonstrated that PLAC8 is strongly ectopically expressed in advanced preneoplastic lesions and invasive human PDAC. However, the molecular function of PLAC8 remained unclear, and accumulating evidence suggested its role is highly dependent on cellular and physiologic context. Here, we demonstrate that in contrast to other cellular systems, PLAC8 protein localizes to the inner face of the plasma membrane in pancreatic cancer cells, where it interacts with specific membranous structures in a temporally and spatially stable manner. Inhibition of PLAC8 expression strongly inhibited pancreatic cancer cell growth by attenuating cell-cycle progression, which was associated with transcriptional and/or posttranslational modification of the central cell cycle regulators CDKN1A, retinoblastoma protein, and cyclin D1 (CCND1), but did not impact autophagy. Moreover, Plac8 deficiency significantly inhibited tumor formation in genetically engineered mouse models of pancreatic cancer. Together, our findings establish PLAC8 as a central mediator of tumor progression in PDAC and as a promising candidate gene for diagnostic and therapeutic targeting. PMID- 26669867 TI - Prevalence of Shigella among diarrheic children under-5 years of age attending at Mekelle health center, north Ethiopia. AB - BACKGROUND: Shigellosis is recognized as a major global public health problem especially in developing countries particularly in children under-5 years of age. Therefore; the objective of this study was to determine the prevalence of Shigella among diarrheic children under-5 years of age attending at Mekelle health center, north Ethiopia. METHODS: A cross-sectional study was conducted among diarrheic children under-5 years of age from March to May, 2012. Structured questionnaire was used to collect the data. Study participants were recruited by convenience sampling technique. Shigella was isolated and identified using standard bacteriological techniques. RESULTS: A total of 241 study participants were included in the study. The overall prevalence of Shigella in this study was 13.3% (32/241). High prevalence of Shigella (22.6%) was revealed from the age group of 12-23 months. No Shigella was isolated from the age group of 0-5 months. Majority of the isolates of Shigella were from bloody and mucoid diarrhea. CONCLUSION: There was high prevalence of Shigella infection in this study. Children among the age group of 12-23 months were highly affected. Therefore; responsible bodies should work hard on preventive measures to reduce or eradicate the problem occurred due to shigellosis. PMID- 26669868 TI - Regarding the Content and Goals of UIM/EJU. AB - The successful collaboration among Ultraschall in der Medizin/ European Journal of Ultrasound (UiM/EJU), DEGUM, OGUM and SGUM as well as Thieme Verlag was confirmed in the respective general meetings in Davos recently, and it was agreed that such cooperation should continue in coming years. Last year, in discussions with the previous DEGUM board of directors the issue of orientation of the content of UiM/EJU, among other things, was an essential topic. Briefly stated, the constructive criticism was: too much science, too little continuing education. It is worthwhile and necessary to address this criticism.The purpose of our clinically-oriented journal is to present the state of the art of multidisciplinary ultrasound in medicine, consistent with the objectives of scientific organizations as well to promote the analysis and communication of this medical technology to the user. This balancing act is difficult for our journal; the limited scope and high number of manuscript submissions result in a rejection rate of over 80 %. Consequently it is hardly possible to cover all special fields in every edition. Nevertheless, in almost 20 years of editorial activity, we have received fewer than five letters from readers criticizing our selection of content.As a journal with German roots, the bilingual diversified CME contributions represent the core of our continuing education opportunities, including pictorial essays and case reports, as well as consensus papers and articles on quality control. In conjunction with the EFSUMB, a series of guidelines has been published, available to everyone - not just subscribers of UiM/EJU. Guidelines are important, since they have an influence on the practice and quality of ultrasound applications in diagnosis and therapy. Calculated in terms of pages and percentages, this is more than just a little, since clinically related scientific articles also represent the requirement for continuing education within the rules of the medical profession.Considered retrospectively, contents of recent volumes of UiM/EJU - apart from the large block of obstetrical articles - were dominated by CEUS, elastography, the breast and "small parts".Although CEUS has been established scientifically 1 2 3 4, but not really employed everywhere, additional articles are needed in order to help integrate the use of contrast agents in routine practice apart from examination of the liver 5 6 7 8 9 10. Likewise, we have endeavored to support elastography as a new technical feature of sonography. Examples of this are publications regarding its use in diagnosing diseases of the liver 11 12 13 14 15, breast 16 17 18 19 and the thyroid 20, as well as its use in examining the pancreas 21 and gastrointestinal tract 22.In addition, for the benefit of sonographers, who are used to observing associated fields from the sidelines, we have presented unexpected highlights, such as articles on peripheral nerves 23 24 25.The contents of this year's final edition present the common interdisciplinary perspective of the editorial team. In addition to a CME article on elastography in the diagnosis of breast cancer 26, we would particularly refer you to two prospective articles: on the importance of CEUS in the aftercare of colon cancer 27 and the value of high-frequency examination of the liver surface compared to elastography and laparoscopy when cirrhosis is suspected 28.Further articles on elastography 29 30 31 32 indicate that the possibilities and limitations of this technology have yet to be reached.As editors, we will be satisfied if the publication interests as many readers as possible, be it online or in the print version, and that they are able to read about new as well as established techniques. We are certain that the societies for ultrasound in medicine, UiM/EJU, and "our sonographic community" are excited to learn about scientific advancements, and we are pleased when, thanks to submissions by our active and innovative authors together with reviewers and our advisory committee, we can set our sights on new topics. PMID- 26669869 TI - EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Short Version). AB - This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online). PMID- 26669870 TI - Is Strain Elastography Really a Good Adjunct for Prediction of Malignancy in Soft Tissue Tumours? PMID- 26669872 TI - [Erythropoietic protoporphyria : Clinical manifestations, diagnosis and new therapeutic possibilities]. AB - BACKGROUND: Erythropoietic protoporphyria, the second most common type of the cutaneous porphyrias, is due to an enzymatic deficiency of ferrochelatase, the last enzyme in heme biosynthesis. The enzyme defect leads to an accumulation of protoporphyrin IX in erythrocytes and an elevated excretion of this metabolite in the feces. CLINICAL PRESENTATION: Usually, disease onset is in early infancy, characterized by increased photosensitivity. During or shortly after sunlight exposure, affected individuals suffer from burning, stinging, itching, and pain in sun-exposed skin areas. These symptoms lead to a considerably reduced quality of life and strict avoidance of sunlight exposure. Subacute symptoms include visible changes like edema and erythema. In the further course of the disease, chronic signs such as lichenification and scarring may occur. A severe complication of hepatic protoporphyrin IX accumulation is the development of a potentially life-threatening fulminant liver failure. Therefore, hepatic laboratory tests and ultrasound of the liver should be performed regularly. THERAPY: Traditionally, therapy merely consisted of consequent photoprotection and orally administered beta-carotene. A novel treatment option is afamelanotide (Scenesse(r)), a synthetic analogue of the naturally occurring alpha-melanocyte stimulating hormone. Afamelanotide, administered as a subcutaneous implant, induces eumelanin production, independent of preceding UV light exposure. This may enable patients with erythropoietic protoporphyria to stay in sunlight significantly longer than previously possible without complaints, thus, substantially improving quality of life. PMID- 26669871 TI - EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Long Version). AB - This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version). PMID- 26669873 TI - [Pathogenesis, clinical picture, and current therapy of rosacea]. AB - Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label. PMID- 26669874 TI - Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms. AB - Cortical functioning within the default mode network (DMN) and salience network (SN) is altered in chronic pain patients. The mechanisms underlying these alterations are unknown, but a novel unexamined source is cross-network communication. Aberrant functional connectivity (FC) between the DMN and SN, whose activity is normally anticorrelated, reflects disease severity in many brain disorders. Further, stronger FC between the posterior cingulate cortex (PCC) and anterior insula has been reported in chronic pain, pointing to abnormal DMN-SN interactions. Here, we tested the hypothesis that cross-network FC between the DMN and SN is abnormal in chronic pain, and is related to pain and associated symptoms. We used resting state fMRI to examine FC within and between the DMN and SN in 20 patients with chronic pain due to ankylosing spondylitis and 20 healthy controls. A whole-network analysis revealed that compared to healthy controls, patients exhibited less anticorrelated FC between the SN and DMN, and the degree of cross-network abnormality tracked pain and disease-related symptoms. This suggests that cross-network FC is a metric of functional brain abnormality in chronic pain. In a complementary seed-based analysis, the PCC was strongly connected with the SN and weakly connected with the DMN in chronic pain compared to healthy controls, suggesting that the PCC acts as a hub for altered network interaction. Sensorimotor cortex cross-network FC correlated with measures of physical function, suggesting that physical functioning also impacts brain network interaction in chronic pain. Our study implicates altered communication between brain networks as a key factor underlying chronic pain. PMID- 26669875 TI - Bereaved Siblings' Advice to Health Care Professionals Working With Children With Cancer and Their Families. AB - INTRODUCTION: Siblings of children with cancer experience psychosocial distress during the illness and after bereavement, but often stand outside the spotlight of attention and care. This study explored bereaved siblings' advice to health care professionals (HCPs) working with children with cancer and their families. MATERIALS AND METHODS: In a nationwide Swedish survey of bereaved siblings, 174/240 (73%) participated. Of these, 108 answered an open-ended question about what advice they would give to HCPs working with children with cancer and their families. In this study, responses to this single question were analyzed using content analysis. RESULTS: The most common advice, suggested by 56% of siblings, related to their own support. One third suggested giving better medical information to siblings. Some siblings wanted to be more practically involved in their brother's/sister's care and suggested that HCPs should give parents guidance on how to involve siblings. Other common advice related to psychosocial aspects, such as the siblings' wish for HCPs to mediate hope, yet also realism, and the importance of asking the ill child about what care they wanted. CONCLUSION: Information, communication, and involvement should be emphasized by HCPs to support siblings' psychosocial needs in both the health care setting and within the family. PMID- 26669876 TI - The efficacy of the OSA-18 as a waiting list triage tool for OSA in children. AB - PURPOSE: Sleep disordered breathing (SDB) is common in children, resulting in extensive waiting lists for specialist clinics. There is an urgent need for a valid method of triaging patients and the OSA-18, a disease-specific tool, is an attractive candidate for this role. We aimed to examine the OSA-18 as a measurement tool in detail and to determine whether the score or aspects of it could be used as a screening tool for SDB in children. METHODS: Retrospective analysis of 582 children (6 months to 16.4 years)-216 underwent overnight PSG and 366 overnight oximetry. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. Receiver operating characteristic curve analysis assessed the diagnostic accuracy of the factors for the presence of OSA. Rasch analysis was used to assess the structure of the items (1-18) and categories of response (Likert scale). RESULTS: The CFA with a forced five-factor structure, revealed three factors with Eigenvalues >1, and explained 73.7 % of the variance. EFA resulted in a two-factor structure, explaining 60.3 % of the variance. Assessment of sensitivity and specificity showed a high false-positive rate, irrespective of the factor structure tested. Rasch analysis showed poor discrimination between adjacent categories on the Likert scale. CONCLUSION: This study confirmed that the predictive value of the OSA-18 for SDB severity is weak. Some questions perform better than others statistically, and the seven categories of response introduce significant statistical noise, raising the possibility that modification of the OSA-18 may improve its performance in the prediction of OSA severity. PMID- 26669877 TI - Outcome of TORS to tongue base and epiglottis in patients with OSA intolerant of conventional treatment. AB - PURPOSE: Transoral robotic surgery (TORS) of the tongue base with or without epiglottoplasty represents a novel treatment for obstructive sleep apnea (OSA). The objective was to evaluate the clinical efficacy of TORS of the tongue base with or without epiglottoplasty in patients who had not tolerated or complied with conventional treatment (continuous positive airway pressure or oral appliance). METHODS: Four-year prospective case series. The primary outcome measure was the apnea-hypopnea index (AHI) in combination with the Epworth Sleepiness Score (ESS). Mean oxygen saturation levels (SaO2) before and after TORS on respective sleep studies were also recorded. Secondary outcome measures included operative time and complications. Patient reported outcome measures (PROMs) assessed included voice, swallow and quality of life. RESULTS: Fourteen patients underwent TORS for tongue base reduction with ten having additional wedge epiglottoplasty. A 64 % success rate was achieved with a normal post operative sleep study in 36 % of cases at 6 months. There was a 51 % reduction in the mean AHI (36.3 +/- 21.4 to 21.2 +/- 24.6, p = 0.02) and a sustained reduction in the mean Epworth Sleepiness Score (p = 0.002). Mean SaO2 significantly increased after surgery compared to pre-operative values (92.9 +/- 1.8 to 94.3 +/ 2.5, p = 0.005). Quality of life showed a sustained improvement 3 months following surgery (p = 0.01). No major complications occurred. CONCLUSIONS: TORS of the tongue base with or without epiglottoplasty represents a promising treatment option with minimal morbidity for selected patients with OSA. Long-term prospective comparative evaluation is necessary to validate the findings of this study. PMID- 26669878 TI - Vibrational properties, phonon spectrum and related thermal parameters of beta octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine: a theoretical study. AB - The vibrational spectrum, phonon dispersion curve, and phonon density of states (DOS) of beta-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (beta-HMX) crystal were obtained by molecular simulation and calculations. As results, it was found that the peaks at low frequency (0-2.5 THz) are comparable with the experimental Terahertz absorption and the molecular vibrational modes are in agreement with previous reports. Thermodynamic properties including Gibbs free energy, enthalpy, and heat capacity as functions of temperature were obtained based on the calculated phonon spectrum. The heat capacity at normal temperature was calculated using linear fitting method, with a result consistent with experiments. Graphical Abstract Phonon spectrum and heat capacity of beta octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine from DFT calculation. PMID- 26669879 TI - Theoretical study of the cooperative effects between the triel bond and the pnicogen bond in BF3...NCXH2...Y (X = P, As, Sb; Y = H2O, NH3) complexes. AB - The interplay between the triel bond and the pnicogen bond in BF3...NCXH2...Y (X = P, As, Sb; Y = H2O, NH3) complexes was studied theoretically. Both bonds exhibited cooperative effects, with shorter binding distances, larger interaction energies, and greater electron densities found for the ternary complexes than for the corresponding binary ones. The cooperative effects between the triel bond and the pnicogen bond were probed by analyzing molecular electrostatic potentials, charge transfer, and orbital interactions. The results showed that the enhancement of the triel bond can mainly be attributed to the electrostatic interaction, while the strengthening of the pnicogen bond can be ascribed chiefly to the electrostatic and orbital interactions. In addition, the origins of both the triel bond and the pnicogen bond were deduced via energy decomposition. PMID- 26669880 TI - Pharmacokinetics of Infliximab and Reduction of Treatment for Inflammatory Bowel Diseases. AB - Local or national policy, patients' preferences, safety and/or economic concerns, or reimbursement issues may dictate stopping drug in inflammatory bowel diseases (IBD) patients. Sustained deep remission is an important predictor of a better outcome after anti-tumor necrosis (TNF) factor therapy discontinuation, including infliximab (IFX) in IBD patients, but this is not sufficient to prevent future relapse in these patients. In IBD patients under combotherapy, trough level of infliximab (TRI) could be helpful to choose stopping one of the two drugs. In patients on IFX monotherapy, TRI could help to decide reduction of drug dosing, particularly in IBD patients with supratherapeutic trough levels. Incidental findings of undetectable TRI in patients with deep remission may identify a subset of patients who may be considered for IFX cessation. Controlled trials further assessing this issue are eagerly awaited. Pending these trials, clear international recommendations for discontinuing anti-TNF therapy are needed. PMID- 26669881 TI - Transdural radicular herniation without pseudomeningocele after spinal stenosis surgery: the electric eel sign. PMID- 26669882 TI - Pediatric Gastroduodenal Embolization with a Microvascular Plug. PMID- 26669883 TI - Reply to the Letter to the Editor entitled "Determinants of In-stent Restenosis After Carotid Artery Stenting". PMID- 26669884 TI - Intraarticular Sacroiliac Joint Injection Under Computed Tomography Fluoroscopic Guidance: A Technical Note to Reduce Procedural Time and Radiation Dose. AB - PURPOSE: A technique for computed tomography fluoroscopy (CTF)-guided intraarticular (IA) sacroiliac joint (SIJ) injection was devised to limit procedural time and radiation dose. METHODS: Our Institutional Review Board approved this retrospective analysis and waived the requirement for informed consent. Overall, 36 consecutive diagnostic or therapeutic IA SIJ injections (unilateral, 20; bilateral, 16) performed in 34 patients (female, 18; male, 16) with a mean age of 45.5 years (range 20-76 years) under CTF guidance were analyzed, assessing technical success (i.e., IA contrast spread), procedural time, and radiation dose. RESULTS: All injections were successful from a technical perspective and were free of serious complications. Respective median procedural times and effective doses of SIJ injection were as follows: unilateral, 5.28 min (range 3.58-8.00 min) and 0.11 millisievert (mSv; range 0.07 0.24 mSv); and bilateral, 6.72 min (range 4.17-21.17 min) and 0.11 mSv (range 0.09-0.51 mSv). CONCLUSIONS: Given the high rate of technical success achieved in limited time duration and with little radiation exposure, CTF-guided IA SIJ injection is a practical and low-risk procedure. PMID- 26669885 TI - Determinants of In-stent Restenosis After Carotid Artery Stenting. PMID- 26669886 TI - Regarding "Percutaneous Augmented Peripheral Osteoplasty in Long Bones of Oncologic Patients for Pain Reduction and Prevention of Impeding Pathologic Fracture: The Rebar Concept". PMID- 26669887 TI - Evaporation Behavior and Characterization of Eutectic Solvent and Ibuprofen Eutectic Solution. AB - Liquid eutectic system of menthol and camphor has been reported as solvent and co solvent for some drug delivery systems. However, surprisingly, the phase diagram of menthol-camphor eutectic has not been reported previously. The evaporation behavior, physicochemical, and thermal properties of this liquid eutectic and ibuprofen eutectic solution were characterized in this study. Differential scanning calorimetry (DSC) analysis indicated that a eutectic point of this system was near to 1:1 menthol/camphor and its eutectic temperature was -1 degrees C. The solubility of ibuprofen in this eutectic was 282.11 +/- 6.67 mg mL(-1) and increased the drug aqueous solubility fourfold. The shift of wave number from Fourier transform infrared spectroscopy (FTIR) indicated the hydrogen bonding of each compound in eutectic mixture. The weight loss from thermogravimetric analysis of menthol and camphor related to the evaporation and sublimation, respectively. Menthol demonstrated a lower apparent sublimation rate than camphor, and the evaporation rate of eutectic solvent was lower than the sublimation rate of camphor but higher than the evaporation of menthol. The evaporation rate of the ibuprofen eutectic solution was lower than that of the eutectic solvent because ibuprofen did not sublimate. This eutectic solvent prolonged the ibuprofen release with diffusion control. Thus, the beneficial information for thermal behavior and related properties of eutectic solvent comprising menthol-camphor and ibuprofen eutectic solution was attained successfully. The rather low evaporation of eutectic mixture will be beneficial for investigation and tracking the mechanism of transformation from nanoemulsion into nanosuspension in the further study using eutectic as oil phase. PMID- 26669888 TI - In Vitro Release and Bioavailability of Silybin from Micelle-Templated Porous Calcium Phosphate Microparticles. AB - Developing a promising carrier for the delivery of poorly water-soluble drugs, such as silybin, to improve oral absorption has become a very worthy of consideration. The goal of this study was to prepare a novel porous calcium phosphate microparticle using povidone-mixed micelles as template while evaluating its in vitro and in vivo properties with silybin as a model drug. The particle characterization, in vitro drug release behavior, and pharmacokinetic parameters of the prepared silybin-loaded calcium phosphate microparticle were investigated. The mean particle size was found to be 3.54 +/- 0.32 MUm with a rough surface porous structure. Additionally, the silybin-loaded calcium phosphate microparticle compared with the free silybin showed a prolonged 72-h release in vitro and a higher C max (418.5 +/- 23.7 ng mL(-1)) with 167.5% oral relative bioavailability. A level A in vitro-in vivo correlation (IVIVC), established for the first time, demonstrated an excellent IVIVC of the formulated silybin in oral administration. In conclusion, this povidone-mixed micelle-based microparticle was successfully prepared to enhance the oral bioavailability of silybin. Therefore, application of this novel porous calcium phosphate microparticle holds a significant potential for the development of poorly water soluble drugs. PMID- 26669889 TI - Benzyl Benzoate-Loaded Microemulsion for Topical Applications: Enhanced Dermatokinetic Profile and Better Delivery Promises. AB - Benzyl benzoate (BB) is one of the oldest drugs used for the treatment of scabies and is recommended as the "first-line intervention" for the cost-effective treatment of the disease. Though a promising candidate, its application is reported to be associated with irritation of the skin and eye, resulting in poor patient compliance. Hence, the present study aims to develop BB-loaded topical microemulsion for the safer and effective delivery of BB. Pseudo-ternary phase diagrams with BB as the oily phase itself, along with Tween 80 as surfactant, and mixture of phospholipid and ethanol as the co-surfactant along with aqueous solution as the external phase were constructed and various compositions were formulated. The optimized formulation was characterized for particle-size, zeta potential, drug-content, globule-morphology pH, and refractive-index, whereas evaluated for skin permeation, retention, compliance, and dermatokinetics. The nanosized formulation offered threefold higher drug permeation vis-a-vis plain drug solution across LACA mice abdominal skin. The drug retention of the selected formulation was nearly twice of that from the marketed product, assuring depot formulation and sustained release. The skin histopathology revealed the non irritant nature of the formulation, as no changes in the normal skin histology were observed. The dermatokinetic studies confirmed better permeation and enhanced skin bioavailability of BB to epidermis as well as dermis vis-a-vis the conventional product. The results indicate that the developed lipid-based microemulsion hydrogel can alleviate the concerns associated with BB and can provide a better and safer delivery option in substantial amounts to various skin layers. PMID- 26669890 TI - Chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity. AB - Chondro-osseous respiratory epithelial adenomatoid hamartoma is a rare hamartomatous lesion of the nasal cavity, with only five cases reported in the literature to date. We report the case of a 3-year-old boy who presented with nasal obstruction and a mass in the left nasal cavity. The mass was completely resected on endoscopy. On microscopy, hamartomatous proliferation of respiratory type glands admixed with islands of immature hyaline cartilage, characteristic of chondro-osseous respiratory epithelial adenomatoid hamartoma, was seen. Neither local recurrence nor distant metastasis was observed after 6 month follow up. Recognition of chondro-osseous respiratory epithelial adenomatoid hamartoma as a benign lesion is important to avoid unnecessary surgical procedures. PMID- 26669891 TI - Participation in siblings' birth at home from children's viewpoint. AB - BACKGROUND: partners often participate in childbirth, and the effects on both partners have been intensively investigated, but children's participation is rare in western countries and less studied. Thus, the aim of this study was to explore and construct a comprehensive structure of meaning of Finnish children's experiences of participating in birth of a sibling at home. DESIGN: a phenomenological study based on analysis of open-interview transcripts by Colaizzi's approach and drawings. PARTICIPANTS: seven children aged five to 17 years who participated in birth of a sibling at home. FINDINGS: the children's experience of participating in a sibling's birth was multifaceted. Their feelings varied from joy to worry, they helped their mother and learned from the experience. They chose to participate. They experienced overwhelmingly strong and positive feelings, but were also worried about the well-being of other family members during the birth. Further, younger children were frustrated, especially if the birth took a long time and they were not allowed to do all they wanted, such as going to a birthing pool. It was important for the children to be able to help their mother and support younger siblings. They learned a lot about childbirth from their participation and information given by the adults. The children regarded home as safe, cosy and a better place to give birth than a hospital. The older children also regarded a home birth as a possible choice for them in the future. They celebrated the baby's arrival and remembered the birth day as being joyful and happy. Participation in the sibling's birth made relationships between the children closer and warmer. Children felt hurt when people outside the family were suspicious when told that the baby was born at home. CONCLUSIONS: the children's experience of participating in a sibling's birth at home included varying feelings, learning from their experience and helping mother. The findings could be utilised in parent education if they are going to have their children with them during the childbirth. PMID- 26669892 TI - Whole-genome sequencing of Mycobacterium tuberculosis for rapid diagnostics and beyond. PMID- 26669895 TI - Conceptualising the agency of highly marginalised women: Intimate partner violence in extreme settings. AB - How is the agency of women best conceptualised in highly coercive settings? We explore this in the context of international efforts to reduce intimate partner violence (IPV) against women in heterosexual relationships. Articles critique the tendency to think of women's agency and programme endpoints in terms of individual actions, such as reporting violent men or leaving violent relationships, whilst neglecting the interlocking social, economic and cultural contexts that make such actions unlikely or impossible. Three themes cut across the articles. (1) Unhelpful understandings of gender and power implicit in commonly used 'men-women' and 'victim-agent' binaries obscure multi-faceted and hidden forms of women's agency, and the complexity of agency-violence intersections. (2) This neglect of complexity results in a poor fit between policy and interventions to reduce IPV, and women's lives. (3) Such neglect also obscures the multiplicities of women's agency, including the competing challenges they juggle alongside IPV, differing levels of response, and the temporality of agency. We outline a notion of 'distributed agency' as a multi-level, incremental and non-linear process distributed across time, space and social networks, and across a continuum of action ranging from survival to resistance. This understanding of agency implies a different approach to those currently underpinning policies and interventions. PMID- 26669893 TI - Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. AB - BACKGROUND: Slow and cumbersome laboratory diagnostics for Mycobacterium tuberculosis complex (MTBC) risk delayed treatment and poor patient outcomes. Whole-genome sequencing (WGS) could potentially provide a rapid and comprehensive diagnostic solution. In this prospective study, we compare real-time WGS with routine MTBC diagnostic workflows. METHODS: We compared sequencing mycobacteria from all newly positive liquid cultures with routine laboratory diagnostic workflows across eight laboratories in Europe and North America for diagnostic accuracy, processing times, and cost between Sept 6, 2013, and April 14, 2014. We sequenced specimens once using local Illumina MiSeq platforms and processed data centrally using a semi-automated bioinformatics pipeline. We identified species or complex using gene presence or absence, predicted drug susceptibilities from resistance-conferring mutations identified from reference-mapped MTBC genomes, and calculated genetic distance to previously sequenced UK MTBC isolates to detect outbreaks. WGS data processing and analysis was done by staff masked to routine reference laboratory and clinical results. We also did a microcosting analysis to assess the financial viability of WGS-based diagnostics. FINDINGS: Compared with routine results, WGS predicted species with 93% (95% CI 90-96; 322 of 345 specimens; 356 mycobacteria specimens submitted) accuracy and drug susceptibility also with 93% (91-95; 628 of 672 specimens; 168 MTBC specimens identified) accuracy, with one sequencing attempt. WGS linked 15 (16% [95% CI 10 26]) of 91 UK patients to an outbreak. WGS diagnosed a case of multidrug resistant tuberculosis before routine diagnosis was completed and discovered a new multidrug-resistant tuberculosis cluster. Full WGS diagnostics could be generated in a median of 9 days (IQR 6-10), a median of 21 days (IQR 14-32) faster than final reference laboratory reports were produced (median of 31 days [IQR 21-44]), at a cost of L481 per culture-positive specimen, whereas routine diagnosis costs L518, equating to a WGS-based diagnosis cost that is 7% cheaper annually than are present diagnostic workflows. INTERPRETATION: We have shown that WGS has a scalable, rapid turnaround, and is a financially feasible method for full MTBC diagnostics. Continued improvements to mycobacterial processing, bioinformatics, and analysis will improve the accuracy, speed, and scope of WGS based diagnosis. FUNDING: National Institute for Health Research, Department of Health, Wellcome Trust, British Colombia Centre for Disease Control Foundation for Population and Public Health, Department of Clinical Microbiology, Trinity College Dublin. PMID- 26669896 TI - Perinatal citalopram does not prevent the effect of prenatal stress on anxiety, depressive-like behaviour and serotonergic transmission in adult rat offspring. AB - It is still not clear whether the selective serotonin reuptake inhibitors frequently prescribed to depressed pregnant women improve the behavioural outcome in their children. The current study investigated whether administration of citalopram to pregnant rats could prevent anxiety and depressive-like behaviour induced by gestational stress in their offspring, and restore the expression of serotonin 1A autoreceptors in GABAergic interneurons in the medial prefrontal cortex and dorsal raphe nuclei in males, and of corticotropin-releasing factor type 2 receptors in GABAergic interneurons in the dorsal raphe nuclei in females. Activation of these receptors modulates serotonergic transmission to target areas and is reduced in a sex-dependent manner by prenatal stress. Citalopram (10 mg/kg/day), administered orally from day 7 of gestation until 21 days postpartum, prevented the increase in anxiety in stressed mothers but did not reduce anxiety and depressive-like behaviour in their offspring and even induced depressive-like behaviour in the offspring of control mothers. Citalopram failed to restore the reduction in the expression of serotonin 1A autoreceptors in the prefrontal cortex of males and in corticotropin-releasing factor type 2 receptors in the dorsal raphe nuclei of females induced by prenatal stress. Prenatal citalopram did not prevent the behavioural changes or reduction in serotonergic transmission to target areas induced by prenatal stress. It had adverse behavioural effects in the offspring of control rats, which, together with the lack of any change in prenatally-stressed rats, may be due to inhibition of the foetal serotonin transporter thereby preventing normal development of the serotonin system. PMID- 26669894 TI - Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation. AB - Complex regulatory networks regulate stem cell behavior and contributions to tissue growth, repair, and homeostasis. A full understanding of the networks controlling stem cell self-renewal and differentiation, however, has not yet been realized. To systematically dissect these networks and identify their components, we performed an unbiased, transcriptome-wide in vivo RNAi screen in female Drosophila germline stem cells (GSCs). Based on characterized cellular defects, we classified 646 identified genes into phenotypic and functional groups and unveiled a comprehensive set of networks regulating GSC maintenance, survival, and differentiation. This analysis revealed an unexpected role for ribosomal assembly factors in controlling stem cell cytokinesis. Moreover, our data show that the transition from self-renewal to differentiation relies on enhanced ribosome biogenesis accompanied by increased protein synthesis. Collectively, these results detail the extensive genetic networks that control stem cell homeostasis and highlight the intricate regulation of protein synthesis during differentiation. PMID- 26669897 TI - Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. AB - Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant. PMID- 26669898 TI - Regulation of Skeletal Muscle Stem Cell Quiescence by Suv4-20h1-Dependent Facultative Heterochromatin Formation. AB - Skeletal muscle stem cells (MuSCs) are required for regeneration of adult muscle following injury, a response that demands activation of mainly quiescent MuSCs. Despite the need for dynamic regulation of MuSC quiescence, relatively little is known about the determinants of this property. Here, we show that Suv4-20h1, an H4K20 dimethyltransferase, controls MuSC quiescence by promoting formation of facultative heterochromatin (fHC). Deletion of Suv4-20h1 reduces fHC and induces transcriptional activation and repositioning of the MyoD locus away from the heterochromatic nuclear periphery. These effects promote MuSC activation, resulting in stem cell depletion and impaired long-term muscle regeneration. Genetic reduction of MyoD expression rescues fHC formation and lost MuSC quiescence, restoring muscle regeneration capacity in Suv4-20h1 mutants. Together, these findings reveal that Suv4-20h1 actively regulates MuSC quiescence via fHC formation and control of the MyoD locus, thereby guarding and preserving the stem cell pool over a lifetime. PMID- 26669899 TI - Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects. AB - Human pluripotent stem cells (hPSCs) frequently acquire chromosomal aberrations such as aneuploidy in culture. These aberrations progressively increase over time and may compromise the properties and clinical utility of the cells. The underlying mechanisms that drive initial genomic instability and its continued progression are largely unknown. Here, we show that aneuploid hPSCs undergo DNA replication stress, resulting in defective chromosome condensation and segregation. Aneuploid hPSCs show altered levels of actin cytoskeletal genes controlled by the transcription factor SRF, and overexpression of SRF rescues impaired chromosome condensation and segregation defects in aneuploid hPSCs. Furthermore, SRF downregulation in diploid hPSCs induces replication stress and perturbed condensation similar to that seen in aneuploid cells. Together, these results suggest that decreased SRF expression induces replicative stress and chromosomal condensation defects that underlie the ongoing chromosomal instability seen in aneuploid hPSCs. A similar mechanism may also operate during initiation of instability in diploid cells. PMID- 26669900 TI - HIV-1 integrase inhibition: looking at cofactor interactions. PMID- 26669901 TI - Postpartum thyroid dysfunction in women with autoimmune thyroiditis. AB - INTRODUCTION: Autoimmune thyroiditis (AIT) is a predisposing factor for developing postpartum thyroid dysfunction (PPTD). AIM: To study the characteristics of PPTD in women with AIT. METHODS: Thirty-eight women with pre existing AIT were included in the study. Thyroid-stimulating hormone, free triiodthyronine, free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies were measured and ultrasound evaluation of the thyroid gland was performed in the first trimester of pregnancy and during the first year following delivery. RESULTS: Thyroid dysfunction was recognized in 68.4% of the patients - 28.9% presented with hypothyroidism and 39.5 % with thyrotoxicosis. The immunological and morphological parameters did not differ between euthyroid women and those with thyroid dysfunction. At the end of the postpartum period restoration of euthyroid state (being on the treatment before pregnancy) was observed in 15.4% of patients with PPTD, while 84.6% required increase of the levothyroxine dose. The analysis found a significantly lower volume of the thyroid gland, shorter duration of the disease, a lower dose of levothyroxine before and during gestation in patients with impaired thyroid function at the end of the postpartum period. CONCLUSION: The risk of PPTD in women with AIT predating pregnancy is higher among women with preserved thyroid functional capacity motivating a thorough assessment of thyroid hormone levels and close follow-up of those women during the postpartum period. PMID- 26669903 TI - Exhaled breath condensate pH decreases following oral glucose tolerance test. AB - Exhaled breath condensate (EBC) pH is a widely measured non-invasive marker of airway acidity. However, some methodological aspects have not been thoroughly investigated. The aim of the study was to determine the effect of oral glucose tolerance test (OGTT) on EBC pH in attempt to better standardize its measurement. Seventeen healthy subjects (24 +/- 2 years, 6 men, 11 women) participated in the study. EBC collection and capillary blood glucose measurements were performed before as well as 0, 30, 60 and 120 min after a standardized OGTT test. The rate of respiratory droplet dilution and pH were evaluated in EBC. Blood glucose significantly increased at 30 min and maintained elevation after 60 and 120 min following OGTT. Compared to baseline (7.99 +/- 0.25) EBC pH significantly decreased immediately after OGTT (7.41 +/- 0.47); this drop sustained over 30 (7.44 +/- 0.72) and 60 min (7.62 +/- 0.44) without a significant difference at 120 min (7.78 +/- 0.26). No change was observed in the rate of respiratory droplet dilution. There was no relationship between blood glucose and EBC pH values. Sugar intake may significantly decrease EBC pH. This effect needs to be considered when performing EBC pH studies. Further experiments are also warranted to investigate the effect of diet on other exhaled biomarkers. PMID- 26669902 TI - Challenges in shared decision making in advanced cancer care: a qualitative longitudinal observational and interview study. AB - BACKGROUND: Patients' preferences and expectations should be taken into account in treatment decision making in the last phase of life. Shared decision making (SDM) is regarded as a way to give the patient a central role in decision making. Little is known about how SDM is used in clinical practice in advanced cancer care. OBJECTIVE: To examine whether and how the steps of SDM can be recognized in decision making about second- and third-line chemotherapy. METHODS: Fourteen advanced cancer patients were followed over time using face-to-face in-depth interviews and observations of the patients' out-clinic visits. Interviews and outpatient clinic visits in which treatment options were discussed or decisions made were transcribed verbatim and analysed using open coding. RESULTS: Patients were satisfied with the decision-making process, but the steps of SDM were barely seen in daily practice. The creation of awareness about available treatment options by physicians was limited and not discussed in an equal way. Patients' wishes and concerns were not explicitly assessed, which led to different expectations about improved survival from subsequent lines of chemotherapy. CONCLUSION: To reach SDM in daily practice, physicians should create awareness of all treatment options, including forgoing treatment, and communicate the risk of benefit and harm. Open and honest communication is needed in which patients' expectations and concerns are discussed. Through this, the difficult process of decision making in the last phase of life can be facilitated and the focus on the best care for the specific patient is strengthened. PMID- 26669904 TI - Informal caregivers and detection of delirium in postacute care: a correlational study of the confusion assessment method (CAM), confusion assessment method family assessment method (CAM-FAM) and DSM-IV criteria. AB - OBJECTIVES: Delirium is a common, serious and potentially life-threatening syndrome affecting older adults. This syndrome continues to be under-recognised and under treated by healthcare professionals across all care settings. Older adults who develop delirium have poorer outcomes, higher mortality and higher care costs. The purposes of this study were to correlate the confusion assessment method-family assessment method and confusion assessment method in the detection of delirium in postacute care, to correlate the confusion assessment method family assessment method and diagnostic and statistical manual of mental disorders text revision criteria in detection of delirium in postacute care, to determine the prevalence of delirium in postacute care elders and to describe the relationship of level of cognitive impairment and delirium in the postacute care setting. Implications for Practice Delirium is disturbing for patients and caregivers. Frequently . family members want to provide information about their loved one. The use of the CAM-FAM and CAM can give a more definitive determination of baseline status. Frequent observations using both instruments may lead to better recognition of delirium and implementation of interventions to prevent lasting sequelae. METHODS: Descriptive studies determined the strengths of relationship between the confusion assessment method, confusion assessment method-family assessment method, Mini-Cog and diagnostic and statistical manual of mental disorders text revision criteria in detection of delirium in the postacute care setting. RESULTS: Prevalence of delirium in this study was 35%. The confusion assessment method-family assessment method highly correlates with the confusion assessment method and diagnostic and statistical manual of mental disorders text revision criteria for detecting delirium in older adults in the postacute care setting. Persons with cognitive impairment are more likely to develop delirium. Family members recognise symptoms of delirium when asked. DISCUSSION: The confusion assessment method-family assessment method is a valid tool for detection of delirium. IMPLICATIONS FOR PRACTICE: Delirium is disturbing for patients and caregivers. Frequently. family members want to provide information about their loved one. The use of the CAM-FAM and CAM can give a more definitive determination of baseline status. Frequent observations using both instruments may lead to better recognition of delirium and implementation of interventions to prevent lasting sequelae. PMID- 26669905 TI - Pharmacokinetics and lung and muscle concentrations of tulathromycin following subcutaneous administration in white-tailed deer (Odocoileus virginianus). AB - Respiratory tract infections are common in farmed North American white-tailed deer (Odocoileus virginianus). Tulathromycin is approved for use in cattle but not deer but is often employed to treat deer. The pharmacokinetic properties and lung and muscle concentrations of tulathromycin in white-tailed deer were investigated. Tulathromycin was administered to 10 deer, and then, serum, lung, and muscle tulathromycin concentrations were measured using liquid chromatography mass spectrometry (LC-MS). The mean maximal serum tulathromycin concentration in deer was 359 ng/mL at 1.3 h postinjection. The mean area under the serum concentration-time curve, apparent volume of distribution, apparent clearance, and half-life was 4883 ng.h/mL, 208 L/kg, 0.5 L/h/kg, and 281 h (11.7 days), respectively. The maximal tulathromycin concentration in lung and muscle homogenate from a single animal was 4657 ng/g (14 days) and 2264 ng/g (7 days), respectively. The minimum concentrations in lung and muscle were 39.4 ng/g (56 days) and 9.1 ng/g (56 days), respectively. Based on similarity in maximal serum concentrations between deer and cattle and high lung concentrations in deer, we suggest the recommended cattle dosage is effective in deer. Tissue concentrations persisted for 56 days, suggesting a need for longer withdrawal times in deer than cattle. Further tissue distribution and depletion studies are necessary to understand tulathromycin persistence in deer tissue; clinical efficacy studies are needed to confirm the appropriate dosage regimen in deer. PMID- 26669906 TI - Stimuli-Responsive Shapeshifting Mesoporous Silica Nanoparticles. AB - Stimuli-responsive materials have attracted great interest in catalysis, sensing, and drug delivery applications and are typically constituted by soft components. We present a one-pot synthetic method for a type of inorganic silica-based shape change material that is responsive to water vapor exposure. After the wetting treatment, the cross-sectional shape of aminated mesoporous silica nanoparticles (MSNs) with hexagonal pore lattice changed from hexagonal to six-angle-star, accompanied by the loss of periodic mesostructural order. Nitrogen sorption measurements suggested that the wetting treatment induced a shrinkage of mesopores resulting in a broad size distribution and decreased mesopore volume. Solid-state (29)Si nuclear magnetic resonance (NMR) spectroscopy of samples after wetting treatment displayed a higher degree of silica condensation, indicating that the shape change was associated with the formation of more siloxane bonds within the silica matrix. On the basis of material characterization results, a mechanism for the observed anisotropic shrinkage is suggested based on a buckling deformation induced by capillary forces in the presence of a threshold amount of water vapor available beyond a humidity of about 50%. The work presented here may open a path toward novel stimuli-responsive materials based on inorganic components. PMID- 26669907 TI - The presence of carbon nanostructures in bakery products induces metabolic stress in human mesenchymal stem cells through CYP1A and p53 gene expression. AB - Ingredients commonly present in processed foods are excellent substrates for chemical reactions during modern thermal cooking or processing, which could possibly result in deteriorative carbonization changes mediated by a variety of thermal reactions. Spontaneous self-assembling complexation or polymerization of partially combusted lipids, proteins, and other food macromolecules with synthetic food additives during high temperature food processing or baking (200 250 degrees C) would result in the formation of carbon nanostructures (CNs). These unknown nanostructures may produce adverse physiological effects or potential health risks. The present work aimed to identify and characterize the nanostructures from the crusts of bread. Furthermore, a toxicological risk assessment of these nanostructures was conducted using human mesenchymal stem cells (hMSCs) as a model for cellular uptake and metabolic oxidative stress, with special reference to induced adipogenesis. CNs isolated from bread crusts were characterized using transmission electron microscopy. The in vitro risk assessment of the CNs was carried out in hMSCs using an MTT assay, cell morphological assessment, a reactive oxygen species assay, a mitochondrial trans membrane potential assay, cell cycle progression assessment and gene expression analysis. Our results revealed that bread crusts contain CNs, which may form during the bread-making process. The in vitro results indicate that carbon nanostructures have moderately toxic effects in the hMSCs at a high dose (400 MUg/mL). The mitochondrial trans-membrane potentials and intracellular ROS levels of the hMSCs were altered at this dose. The levels of the mRNA transcripts of metabolic stress-responsive genes such as CAT, GSR, GSTA4, CYP1A and p53 were significantly altered in response to CNs. PMID- 26669908 TI - Autologous cell sources in therapeutic vasculogenesis: In vitro and in vivo comparison of endothelial colony-forming cells from peripheral blood and endothelial cells isolated from adipose tissue. AB - BACKGROUND AIMS: Autologous endothelial cells are promising alternative angiogenic cell sources in trials of therapeutic vasculogenesis, in the treatment of vascular diseases and in the field of tissue engineering. A population of endothelial cells (ECs) with long-term proliferative capability, endothelial colony-forming cells (ECFCs), can be isolated from human peripheral blood. ECFCs are considered an endothelial precursor population. They can be expanded in cell factories in sufficient numbers for clinical applications, but because the number of isolated primary ECs is low, the culture period required may be long. Another EC population that is easily available in the autologous setting and may be expanded in vitro through several population doublings are ECs from adipose tissue (AT-ECs). METHODS: Through extensive comparisons using whole-genome microarray analysis, morphology, phenotype and functional assays, we wanted to evaluate the potential of these EC populations for use in clinical neovascularization. RESULTS: Global gene expression profiling of ECFCs, AT-ECs and the classical EC population, human umbilical vein ECs, showed that the EC populations clustered as unique populations, but very close to each other. By cell surface phenotype and vasculogenic potential in vitro and in vivo, we also found the ECFCs to be extremely similar to AT-ECs. CONCLUSIONS: These properties, together with easy access in the autologous setting, suggest that both AT-ECs and ECFCs may be useful in trials of therapeutic neovascularization. However, AT-ECs may be a more practical alternative for obtaining large quantities of autologous ECs. PMID- 26669909 TI - Development of viable TAP-tagged dengue virus for investigation of host-virus interactions in viral replication. AB - Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast two-hybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions. PMID- 26669910 TI - Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis. AB - OBJECTIVE: Discrimination of diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) can be challenging. Usefulness of whole-body magnetic resonance imaging (WB-MRI) in diagnosing spondyloarthritis has been recently proved. We assessed the value of clinical variables alone and in combination with WB-MRI to distinguish between DISH and AS. METHODS: Diagnostic case-control study: 33 patients with AS and 15 patients with DISH were included. All patients underwent 1.5 Tesla WB-MRI scanning. MR scans were read by a blinded radiologist using the Canadian-Danish Working Group's recommendation. Imaging and clinical variables were identified using the bootstrap. The most important variables from MR and clinical history were assessed in a multivariate fashion resulting in 3 diagnostic models (MRI, clinical, and combined). The discriminative capacity was quantified using the area under the receiver-operating characteristic (ROC) curve. The strength of diagnostic variables was quantified with OR. RESULTS: Forty-eight patients provided 1545 positive findings (193 DISH/1352 AS). The final MR model contained upper anterior corner fat infiltration (32 DISH/181 AS), ankylosis on the vertebral endplate (4 DISH/60 AS), facet joint ankylosis (4 DISH/49 AS), sacroiliac joint edema (11 DISH/91 AS), sacroiliac joint fat infiltration (2 DISH/114 AS), sacroiliac joint ankylosis (2 DISH/119 AS); area under the ROC curve was 0.71, 95% CI 0.64-0.78. The final clinical model contained patient's age and body mass index (area under the ROC curve 0.90, 95% CI 0.89-0.91). The full diagnostic model containing clinical and MR information had an area under the ROC curve of 0.93 (95% CI 0.92-0.95). CONCLUSION: WB-MRI features can contribute to the correct diagnosis after a thorough conventional workup of patients with DISH and AS. PMID- 26669911 TI - Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis. AB - OBJECTIVE: The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts. METHODS: Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis. RESULTS: We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa- in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa- were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and alpha enolase. CONCLUSION: In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo. PMID- 26669912 TI - Safety and Efficacy of Subcutaneous Golimumab in Patients with Active Rheumatoid Arthritis despite Methotrexate Therapy: Final 5-year Results of the GO-FORWARD Trial. AB - OBJECTIVE: To evaluate the safety and efficacy of golimumab (GOL), a human antitumor necrosis factor antibody, in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy through 5 years in the GO-FORWARD trial. METHODS: Patients with active RA despite MTX therapy were randomly assigned to receive placebo + MTX (Group 1), GOL 100 mg + placebo (Group 2), GOL 50 mg + MTX (Group 3), or GOL 100 mg + MTX (Group 4). Patients in groups 1, 2, and 3 with inadequate response could enter early escape at Week 16 to GOL 50 mg + MTX or GOL 100 mg + MTX, and all remaining Group 1 patients crossed over to GOL 50 mg + MTX at Week 24. The blind was maintained through the 52-week database lock, after which treatment adjustments were permitted. Adverse events (AE) were monitored through Week 268. Efficacy was evaluated using the American College of Rheumatology (ACR) 20/50/70 responses and a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP). Response rates at Week 256 were analyzed by an intent-to-treat analysis. RESULTS: A total of 444 patients were randomized, and 313 received GOL through Week 252; 301 patients completed the safety followup through Week 268. Infections were the most common type of AE; 172 patients (39.6%) had >= 1 serious AE. No unexpected safety signals were observed. At Week 256, ACR20/50/70 responses were achieved by 63.1%, 40.8%, and 24.1%, respectively, of all randomized patients. About 78% of all patients achieved a good or moderate DAS28-CRP response. CONCLUSION: Improvements in the signs and symptoms of RA were maintained through 5 years. AE through 5 years were consistent with earlier reports of the GO-FORWARD trial; no apparent increased risk was observed over time. PMID- 26669913 TI - Methotrexate Efficacy in the Tight Control in Psoriatic Arthritis Study. AB - OBJECTIVE: Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug in psoriatic arthritis, but there is conflicting evidence to support its efficacy. METHODS: Within the Tight Control of Psoriatic Arthritis (TICOPA) study, patients were treated with MTX as part of the tight control protocol or standard care. Outcomes were recorded at the 12-week visit, including joint counts, skin, nail, enthesitis, dactylitis, and patient-reported measures. RESULTS: Of the 206 patients enrolled, 188 received MTX in the first 12 weeks of the trial with 104 receiving a mean dose > 15 mg/week. The proportions of patients achieving the American College of Rheumatology (ACR) outcomes at 12 weeks were ACR20 40.8%, ACR50 18.8%, and ACR70 8.6%, with 22.4% achieving minimal disease activity. Improvements were seen in psoriasis with 27.2% reaching a Psoriasis Area and Severity Index (PASI) 75. The proportion of patients with dactylitis and Leeds dactylitis instrument (LDI) scores decreased significantly (62.7% decrease in patients with dactylitis, median change LDI -59.7, -157.4 to 26.4, p = 0.033). The decrease in proportion of patients with enthesitis (25.7%) was significant, but the median change in enthesitis score was 0. There was a trend to higher proportions of patients receiving over 15 mg/week achieving ACR20, ACR50, and PASI75. CONCLUSION: Despite the open-label design of the data, improvements in multiple clinical outcomes were seen. The proportion of patients reaching ACR20 in the TICOPA study was higher than in the Methotrexate in Psoriatic Arthritis study (41% vs 34%), but no comparative data are available for other outcomes. There is a suggestion of a dose response, but this is hard to assess when patients doing well may be maintained on lower doses. PMID- 26669915 TI - Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Prevalence and Predictors. AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) prevalence has been reported to be between 0.5% and 17% in systemic lupus erythematosus (SLE). This study assessed PAH prevalence and predictors in an SLE cohort. METHODS: The Borg dyspnea scale, DLCO, N-terminal pro-brain natriuretic peptide (NT-proBNP), and Doppler echocardiographic (DE) were performed. An echocardiographic Doppler exercise test was conducted in selected patients. When DE systolic pulmonary arterial pressure was >= 45 mmHg or increased during exercise > 20 mmHg, a right heart catheterization was performed. Hemodynamic during exercise was measured if rest mean pulmonary arterial pressure was < 25 mmHg. RESULTS: Of the 203 patients with SLE, 152 were included. The mean age was 44.9 +/- 12.3 years, and 94% were women. Three patients had known PAH. The algorithm diagnosed 1 patient with chronic thromboembolic pulmonary hypertension and 5 with exercise-induced pulmonary artery pressure increase (4 with occult left diastolic dysfunction). These patients had significantly more dyspnea, higher NT-proBNP, and lower DLCO. CONCLUSION: These data confirm the low prevalence of PAH in SLE. In our cohort, occult left ventricular diastolic dysfunction was a frequent diagnosis of unexplained dyspnea. Dyspnea, DLCO, and NT-proBNP could be predictors of pulmonary hypertension in patients with SLE. PMID- 26669914 TI - Variations in Hip Shape Are Associated with Radiographic Knee Osteoarthritis: Cross-sectional and Longitudinal Analyses of the Johnston County Osteoarthritis Project. AB - OBJECTIVE: Hip shape by statistical shape modeling (SSM) is associated with hip radiographic osteoarthritis (rOA). We examined associations between hip shape and knee rOA given the biomechanical interrelationships between these joints. METHODS: Bilateral baseline hip shape assessments [for those with at least 1 hip with a Kellgren-Lawrence arthritis grading scale (KL) 0 or 1] from the Johnston County Osteoarthritis Project were available. Proximal femur shape was defined on baseline pelvis radiographs and evaluated by SSM, producing mean shape and continuous variables representing independent modes of variation (14 modes = 95% of shape variance). Outcomes included prevalent [baseline KL >= 2 or total knee replacement (TKR)], incident (baseline KL 0/1 with followup >= 2), and progressive knee rOA (KL increase of >= 1 or TKR). Limb-based logistic regression models for ipsilateral and contralateral comparisons were adjusted for age, sex, race, body mass index (BMI), and hip rOA, accounting for intraperson correlations. RESULTS: We evaluated 681 hips and 682 knees from 342 individuals (61% women, 83% white, mean age 62 yrs, BMI 29 kg/m(2)). Ninety-nine knees (15%) had prevalent rOA (4 knees with TKR). Lower modes 2 and 3 scores were associated with ipsilateral prevalent knee rOA, and only lower mode 3 scores were associated with contralateral prevalent knee rOA. No statistically significant associations were seen for incident or progressive knee rOA. CONCLUSION: Variations in hip shape were associated with prevalent, but not incident or progressive, knee rOA in this cohort, and may reflect biomechanical differences between limbs, genetic influences, or common factors related to both hip shape and knee rOA. PMID- 26669916 TI - Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study. AB - OBJECTIVE: To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA. METHODS: Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician. RESULTS: A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX. CONCLUSION: ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms. TRIAL REGISTRATION: Clinicaltrials.gov NCT01111240. PMID- 26669917 TI - Effectiveness of an Integrated Multidisciplinary Osteoarthritis Outpatient Program versus Outpatient Clinic as Usual: A Randomized Controlled Trial. AB - OBJECTIVE: Osteoarthritis (OA) is one of the leading causes of pain and disability. Given the constraint in the provision of care, there is a need to develop and assess effectiveness of new treatment models. The objective was to compare satisfaction with and effectiveness of a new integrated multidisciplinary outpatient program with usual care in an outpatient clinic for patients with OA. METHODS: Patients with clinical OA referred to a rheumatology outpatient clinic were randomized to a 3.5-h multidisciplinary group-based educational program followed by individual consultations, or to usual care. The primary outcome was satisfaction with the health service evaluated on a numerical rating scale (0 = extremely unsatisfied, 10 = extremely satisfied) after 4 months. Secondary outcomes included health-related quality of life measures. RESULTS: Of 391 patients, 86.4% (n = 338) were women, and mean age was 61.2 (SD 8.0) years. At 4 months, patients who received integrated multidisciplinary care were significantly more satisfied with the health service compared with controls, with a mean difference of -1.05 (95% CI -1.68 to -0.43, p < 0.001). Among secondary outcomes, only self-efficacy with other symptoms scale (10-100) improved significantly in the multidisciplinary group compared with controls at 4 months (3.59, 95% CI 0.69-6.5, p = 0.02). At 12 months, the Australian/Canadian Hand Osteoarthritis Index pain (0-10) and fatigue scores (0-10) were slightly worse in the multidisciplinary group with differences of 0.38 (95% CI 0.06-0.71, p = 0.02) and 0.55 (95% CI 0.02-1.07, p = 0.04), respectively. CONCLUSION: Patients receiving an integrated multidisciplinary care model were more satisfied with healthcare than those receiving usual care, whereas there were no clinically relevant improvements in health outcomes. PMID- 26669918 TI - Defining Low Disease Activity States in Psoriatic Arthritis using Novel Composite Disease Instruments. AB - OBJECTIVE: To explore the relationship between minimal disease activity (MDA) and the low disease activity cutoffs of the Psoriatic ArthritiS Disease Activity Score (PASDAS) and the Composite Psoriatic Disease Activity Index (CPDAI). METHODS: Data from the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) composite exercise (GRACE) study were used for these analyses. Alternative definitions of low disease activity were used with 6/7 and 7/7 of MDA items, and a criteria set mandating the 2 articular items and 3/5 alternate items (MDA-joints). Two reference questions were used as anchors: physician's global opinion of MDA, and patient's opinion on their disease control. RESULTS: Substantial agreement was found between MDA, MDA-joints, PASDAS, and CPDAI. Compared to the 2 reference questions, the various definitions of low disease activity gave sensitivities that were generally worse than specificities, the latter being high (> 0.9) in most cases. Both PASDAS and CPDAI demonstrated good discrimination between the "low" and "high" disease activity states by all the MDA definitions. Using these data, with an MDA of 7/7 to define a very low disease cutoff, the corresponding values for PASDAS and CPDAI were 1.9 and 2, respectively. CONCLUSION: An MDA score of 7/7 is proposed as very low disease activity in psoriatic arthritis. Using this definition, the equivalent cutoffs for PASDAS and CPDAI are 1.9 and 2, respectively. PMID- 26669919 TI - Safety and Efficacy of Open-label Subcutaneous Ixekizumab Treatment for 48 Weeks in a Phase II Study in Biologic-naive and TNF-IR Patients with Rheumatoid Arthritis. AB - OBJECTIVE: To evaluate ixekizumab, an anti-interleukin 17A monoclonal antibody, for safety and effectiveness through 64 weeks in biologic-naive and tumor necrosis factor-inadequate responder (TNF-IR) patients with rheumatoid arthritis. METHODS: Patients completing the 16-week double-blind period of a phase II study were eligible to enter the open-label extension (OLE) for an additional 48 weeks of ixekizumab treatment. After a treatment hiatus between weeks 10 to 16, 232 biologic-naive and 158 TNF-IR patients entered the OLE with all patients receiving 160 mg ixekizumab at weeks 16, 18, and 20, and then every 4 weeks through Week 64. RESULTS: A total of 201 (87%) biologic-naive and 99 (62%) TNF-IR patients completed the OLE. Treatment-emergent adverse events (AE) occurred in 168 (72%) biologic-naive and 115 (73%) TNF-IR patients during the OLE. Most AE were mild to moderate in severity and did not lead to study discontinuation. Serious AE (SAE) occurred in 17 (7%) biologic-naive patients, including 5 (2%) serious infections and 2 (1%) deaths. SAE occurred in 18 (11%) TNF-IR patients, including 4 (3%) serious infections and 1 (1%) death. No mycobacterial or invasive fungal infections were reported. Clinical responses [American College of Rheumatology (ACR) 20, ACR50, ACR70, and 28-joint Disease Activity Score with C reactive protein] observed at Week 16 were maintained or improved through Week 64. CONCLUSION: Ixekizumab was well tolerated, and safety findings in the OLE were consistent overall with those in the double-blind period of this study. Clinical improvements observed with ixekizumab through Week 16 were maintained or improved in patients participating in the OLE through Week 64. TRIAL REGISTRATION NUMBER: NCT00966875. PMID- 26669920 TI - Retrospective Comparison of Open versus Endovascular Procedures for Takayasu Arteritis. AB - OBJECTIVE: To compare the outcomes between vascular surgery and endovascular procedures in a cohort of patients with Takayasu arteritis (TA). METHODS: A retrospective cohort study was conducted of patients with TA who underwent vascular interventions at a tertiary center between 1984 and 2009. The American College of Rheumatology criteria for TA were used to select patients. Disease activity was assessed according to the Kerr criteria. Data are reported using descriptive statistics and Kaplan-Meier methods for complication rates. RESULTS: The cohort included 66 patients with TA who underwent 119 vascular procedures (surgery 93; endovascular repair 26). The most frequent indication for vascular surgery and endovascular procedure was arm claudication (surgical group 43%, endovascular repair group 31%). In 59% of the vascular surgical procedures and in 38% of endovascular procedures, the disease was active within 1 month of intervention. The most frequent arterial lesion requiring intervention was the aorta (28%) in the vascular surgery group and the subclavian (35%) in the endovascular repair group. Early complications occurred after 15 surgeries and 4 endovascular repair procedures (p = 0.93). Late complications occurred after 34 surgical procedures and 10 endovascular repair procedures (44% vs 66%, respectively; p = 0.33). The majority of complications in both groups were restenosis. Hypertension, dyslipidemia, and higher doses of corticosteroids were associated with an increased risk of postprocedural complications and restenosis. CONCLUSION: In patients with TA, both open surgical and endovascular revascularization procedures are associated with high failure rates and frequent operative complications. Traditional cardiovascular risk factors, corticosteroid dose, and active disease are risk factors for restenosis after revascularization procedures. PMID- 26669921 TI - Disability with Persistent Pain Following an Epidemic of Chikungunya in Rural South India. AB - OBJECTIVE: We investigated the effects of chronic rheumatic and musculoskeletal symptoms on the functional status of people affected by the chikungunya (CKG) epidemic in the Calicut District, Kerala, South India in 2009. METHODS: A cross sectional house-to-house survey was conducted 18 months after the CKG epidemic to assess functional status of individuals with post-epidemic persistent pain. All respondents over age 15 years with persistent pain fitting the epidemiological case definition were included. Participants' functional status was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Factors affecting severity of HAQ-DI were analyzed by ordinal regression. RESULTS: Of 3869 subjects interviewed, 1195 (34.3%) had a positive history of CHIKV virus infection (epidemiological or confirmed); 36.28% (624/1720) of CKG-affected individuals had persistent pain 18 months post epidemic. Mean age of those affected was 48.22 +/- 15.6 years; 23.2% had no disability, while 16.2% had moderate to severe disability on the HAQ-DI. Significant factors affecting severity of disability on HAQ-DI included previous rheumatic musculoskeletal disease (OR 2.27), joint and soft-tissue involvement (OR 3.74), only joint involvement (OR 2.14), female sex (OR 1.44), diet (OR 4.73), and history of joint swelling (OR 1.72). CONCLUSION: Persistence of pain noted in post-CKG disease resulted in significantly deteriorated functional status of those affected. PMID- 26669922 TI - Comorbidities Associated with Psoriatic Arthritis Compared with Non-psoriatic Spondyloarthritis: A Cross-sectional Study. AB - OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory skeletal disease associated with health concerns such as obesity, Type II diabetes, dyslipidemia, hypertension (HTN), and cardiovascular (CV) disease. The involvement of these metabolic factors in the pathogenesis, severity, and progression of PsA remains unclear. In our study, we compared comorbidities associated with PsA to those patients with related but non-PsA forms of spondyloarthritis (SpA). METHODS: The SpA database at the Rheumatology Department of University Hospitals Leuven was analyzed in a cross-sectional manner using the demographic, medical, and laboratory information of 518 patients with PsA and non-PsA SpA. The patients were grouped by their diagnosis and evaluated on the basis of sex, age, education, work status, disease duration, treatment, and type and number of comorbidities. The data were assessed using the chi-square test, Student t test, Fisher's exact test, and logistic regression, including correction for multiple testing. RESULTS: Out of the 518 patients (62.74% men, 37.25% women), 53.66% had comorbidities. The PsA group had 262 patients (mean age 58.8 yrs) and the non-PsA SpA group had 256 patients (mean age 44.9 yrs, p < 0.001). The PsA group was found to have more and multiple comorbidities compared with non-PsA SpA (p < 0.001). The CV and metabolic comorbidities were also significantly higher in the PsA group (p < 0.001). Coronary artery disease, HTN, hyperlipidemia, and metabolic syndrome showed a marked difference between the 2 groups (p < 0.05). An increased incidence of malignancy was found in PsA group (p < 0.05). CONCLUSION: Comorbidities and malignancies are increased in patients with PsA compared with non-PsA SpA, irrespective of demographic factors and type of treatment. PMID- 26669923 TI - SMAD3 Is Upregulated in Human Osteoarthritic Cartilage Independent of the Promoter DNA Methylation. AB - OBJECTIVE: To compare SMAD3 gene expression between human osteoarthritic and healthy cartilage and to examine whether expression is regulated by the promoter DNA methylation of the gene. METHODS: Human cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary osteoarthritis (OA), and from patients with hip fractures as controls. DNA/RNA was extracted from the cartilage tissues. Real-time quantitative PCR was performed to measure gene expression, and Sequenom EpiTyper was used to assay DNA methylation. Mann-Whitney test was used to compare the methylation and expression levels between OA cases and controls. Spearman rank correlation coefficient was calculated to examine the association between the methylation and gene expression. RESULTS: A total of 58 patients with OA (36 women, 22 men; mean age 64 +/- 9 yrs) and 55 controls (43 women, 12 men; mean age 79 +/- 10 yrs) were studied. SMAD3 expression was on average 83% higher in OA cartilage than in controls (p = 0.0005). No difference was observed for DNA methylation levels in the SMAD3 promoter region between OA cases and controls. No correlation was found between SMAD3 expression and promoter DNA methylation. CONCLUSION: Our study demonstrates that SMAD3 is significantly overexpressed in OA. This overexpression cannot be explained by DNA methylation in the promoter region. The results suggest that the transforming growth factor-beta/SMAD3 pathway may be overactivated in OA cartilage and has potential in developing targeted therapies for OA. PMID- 26669924 TI - Obesity Is Common in Axial Spondyloarthritis and Is Associated with Poor Clinical Outcome. AB - OBJECTIVE: To assess the prevalence of overweight and obesity in a large cohort of patients with axial spondyloarthritis (axSpA) in comparison with the general population. To explore the relationship of body mass index (BMI) with clinical outcome in axSpA. METHODS: Patients from the Groningen Leeuwarden Axial SpA cohort who visited the outpatient clinic in 2011/2012 were included in this cross sectional analysis. Body weight, height, disease activity, physical function, and quality of life (QoL) were assessed. Patients were divided into normal weight (BMI < 25 kg/m(2)), overweight (BMI >= 25 to < 30 kg/m(2)), and obese (BMI >= 30 kg/m(2)). BMI data for the general population in the same demographic region, matched for age and sex, were obtained from the LifeLines Cohort Study. RESULTS: Of the 461 patients with axSpA, 37% were overweight and 22% were obese. In the LifeLines cohort (n = 136,577), 43% were overweight and 15% were obese. Overweight and obese patients were older, had longer symptom duration, and had more comorbidities, especially hypertension. Further, obese patients had significantly higher disease activity, worse physical function, and worse QoL than overweight and normal weight patients (mean Bath Ankylosing Spondylitis Disease Activity Index 4.5, 3.5, 3.8; mean Ankylosing Spondylitis Disease Activity Score 2.8, 2.2, 2.3; median C-reactive protein 5, 3, 3 mg/l; median erythrocyte sedimentation rate 13, 8, 8 mm/h; median Bath Ankylosing Spondylitis Functional Index 5.2, 2.9, 2.9; median Ankylosing Spondylitis QoL Questionnaire 8, 4, 5, respectively). After adjustment for potential confounders, obesity proved to be an independent predictor of worse clinical outcome. CONCLUSION: In this large observational cohort study, obesity is more common in axSpA than in the general population and it is associated with worse clinical outcome. PMID- 26669925 TI - Minimal Disease Activity and Remission in Psoriatic Arthritis Patients Treated with Anti-TNF-alpha Drugs. AB - OBJECTIVE: A state of remission is the target of therapy in chronic arthritis. The aim of the present study was to assess the rate of minimal disease activity (MDA) and remission in patients with psoriatic arthritis (PsA) treated with tumor necrosis factor (TNF-alpha) blockers. Disease characteristics and predictors of MDA were also evaluated. METHODS: Patients fulfilling the ClASsification for Psoriatic ARthritis (CASPAR) criteria and treated with TNF-alpha blockers adalimumab, etanercept, or golimumab were enrolled and prospectively followed every 4 months for 1 year in a clinical practice setting. Patients were considered in MDA when they met at least 5/7 of the criteria previously defined. Other remission criteria evaluated were 28-joint Disease Activity Score-C reactive protein (DAS28-CRP) < 2.6 and Disease Activity in Psoriatic Arthritis (DAPSA) score <= 3.3. Patients achieving MDA were compared to non-MDA to identify outcome predictor factors. RESULTS: Of the 75 patients treated with TNF-alpha blockers, at baseline no patients were in MDA or had a DAPSA score <= 3.3, while 25 (21.3%) had a DAS28-CRP score < 2.6. Five patients (6%) discontinued treatment because of side effects or inefficacy during followup. After 12 months, MDA was achieved in 46 patients (61.3%). No difference was found among the 3 anti-TNF alpha drugs. Predictors for MDA were found to be male sex, high CRP, high erythrocyte sedimentation rate, and low Health Assessment Questionnaire. CONCLUSION: In our prospective observational study, based on a clinical practice setting, MDA was achieved in 61.3% of patients treated with TNF-alpha blockers, identifying this as an achievable target for patients with PsA. Predictors of remission were also identified. PMID- 26669926 TI - Radiologic Changes in the Symphysis Pubis of Male Patients with Ankylosing Spondylitis. AB - OBJECTIVE: We aimed to evaluate the involvement of the symphysis pubis in patients with ankylosing spondylitis (AS), and to assess the correlations between symphysis pubis changes and clinical findings. METHODS: We retrospectively evaluated a total of 222 male patients with AS who underwent pelvic and cervical/lumbar spine radiography at the Hanyang University Hospital for Rheumatic Diseases from August 2004 to February 2014. Radiographs were examined by 2 experienced radiologists, and radiographic damage was scored as follows: 0 (no damage), 1 (subtle irregularity and/or subchondral sclerosis), 2 (erosion), 3 (partial ankylosis), and 4 (total ankylosis). We evaluated the patients' clinical characteristics and analyzed their correlations with radiographic symphysis pubis changes. RESULTS: The mean patient age was 30.5 +/- 8.3 years and mean disease duration was 7.1 +/- 4.6 years; 105 patients (47.3%) exhibited radiologic damage in the symphysis pubis. Moreover, 75, 28, 0, and 2 patients had scores of 1, 2, 3, and 4, respectively. When comparing the normal (score 0) and abnormal (score 1 4) symphysis pubis groups, the latter had a longer symptom duration (10.1 +/- 7.0 vs 7.6 +/- 5.8 yrs, p = 0.004) and higher modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; 18.6 +/- 17.0 vs. 14.3 +/- 13.4, p = 0.038). Moreover, a significant correlation was noted between the radiographic symphysis pubis damage score and mSASSS (r(2) = 0.147, p = 0.029). CONCLUSION: Among male patients with AS, 47.3% exhibited symphysis pubis involvement. Moreover, a correlation was observed between the radiographic symphysis pubis and spine changes. PMID- 26669927 TI - Inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) reduces neonatal hypoxic-ischaemic brain damage. AB - Hypoxic-ischaemic encephalopathy is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy and cognitive disabilities. Hypoxia-ischaemia (HI) strongly up-regulates Signal Transducer and Activator of Transcription 3 (STAT3) in the immature brain. Our aim was to establish whether STAT3 up-regulation is associated with neonatal HI-brain damage and evaluate the phosphorylated STAT3-contribution from different cell types in eliciting damage. We subjected postnatal day seven mice to unilateral carotid artery ligation followed by 60 min hypoxia. Neuronal STAT3-deletion reduced cell death, tissue loss, microglial and astroglial activation in all brain regions. Astroglia-specific STAT3-deletion also reduced cell death, tissue loss and microglial activation, although not as strongly as the deletion in neurons. Systemic pre-insult STAT3-blockade at tyrosine 705 (Y705) with JAK2-inhibitor WP1066 reduced microglial and astroglial activation to a more moderate degree, but in a pattern similar to the one produced by the cell-specific deletions. Our results suggest that STAT3 is a crucial factor in neonatal HI-brain damage and its removal in neurons or astrocytes, and, to some extent, inhibition of its phosphorylation via JAK2-blockade reduces inflammation and tissue loss. Overall, the protective effects of STAT3 inactivation make it a possible target for a therapeutic strategy in neonatal HI. Current data show that neuronal and astroglial STAT3 molecules are involved in the pathways underlying cell death, tissue loss and gliosis following neonatal hypoxia-ischaemia, but differ with respect to the target of their effect. Y705-phosphorylation contributes to hypoxic-ischaemic histopathology. Protective effects of STAT3 inactivation make it a possible target for a therapeutic strategy in neonatal hypoxia-ischaemia. PMID- 26669928 TI - Echocardiographic Diagnosis of Acute Pulmonary Embolism in Patients with McConnell's Sign. AB - BACKGROUND: "McConnell's sign" (McCS), described as hypo- or akinesis of the right ventricular (RV) free wall with preservation of the apex, is associated with acute pulmonary embolism (aPE). However, the sensitivity of McCS for the detection of aPE is limited. We sought to evaluate in patients with McCS, whether echocardiographic parameters of global and regional RV function could differentiate between patients with and without aPE. METHODS: We reviewed echocardiograms of 81 patients with McCS, who underwent CT or V/Q studies for suspected PE, and 40 normal controls (NL). Echocardiograms were analyzed to measure pulmonary artery systolic pressure (PASP), tricuspid regurgitation (TR) by vena contracta width, conventional indices of RV function, and speckle tracking-derived longitudinal free wall strain. ROC analysis was performed to evaluate the diagnostic accuracy of these parameters for diagnosis of aPE. RESULTS: Fifty-five of eighty-one (68%) had PE (McCS + PE), while 26 of 81 (32%) did not (McCS - PE). Compared to NL, global and segmental RV strain were lower in patients with McCS, contrary to the notion of normal apical function. In McCS + PE, compared to McCS - PE: (1) PASP, fractional area change and TR were significantly lower; (2) strain magnitude was significantly lower globally and in basal and apical segments. Individual parameters had similar diagnostic accuracy by ROC analysis, which further improved by combining parameters. In McCS - PE, 69% of patients had pulmonary hypertension (PH). CONCLUSIONS: McCS and aPE are not synonymous. RV free wall strain may aid in differential diagnosis of patients with McCS evaluated for aPE. Specifically, McCS should prompt an inquiry for evidence of PH, which would indicate that aPE is less likely. PMID- 26669929 TI - Prevalence of Intervillous Thrombi Is Increased in Placentas from Pregnancies Complicated by Diabetes. AB - Intervillous thrombus (IVT) is a placental pathology of unclear cause. One possible cause is that IVT protects against fetomaternal transfusion due to trophoblastic disruption. A role for hyperglycemia in trophoblast apoptosis has been suggested. We sought to determine whether placentas from pregnancies complicated by diabetes had an increased incidence of IVT. Medical records of 206 patients with type 1 diabetes (n = 39), type 2 diabetes (n = 37), and gestational diabetes (GDM, n = 130) at the Massachusetts General Hospital were identified. Placental pathology reports were reviewed to determine prevalence of IVT. Gestational and maternal age-matched controls were selected from the pathology archives consisting of placentas examined only for the indication of group B streptococcus screen positivity; controls were confirmed euglycemic and reviewed for IVT. Fisher exact test was used for statistical analysis. An increased incidence of IVT was present in all diabetics (type 1, type 2, and GDM; 32 of 206; 15.5%; P = 0.04) and GDM exclusively (22 of 130; 16.9%; P = 0.03) versus controls (7 of 99; 7.1%). IVT were also increased in patients with type 1 diabetes (4 of 39; 10.3%) and type 2 diabetes (6 of 37; 16.2%) compared to controls (7 of 99; 7.1%), but the results did not attain statistical significance (P = 0.73 and 0.19, respectively). The incidence of IVT was increased in the placentas of patients with diabetes as a group (type 1, type 2, and GDM), and in patients with GDM in particular. This is the first report of an association between diabetes and an increased incidence of placental IVT. PMID- 26669930 TI - CytoGEDEVO-global alignment of biological networks with Cytoscape. AB - MOTIVATION: In the systems biology era, high-throughput omics technologies have enabled the unraveling of the interplay of some biological entities on a large scale (e.g. genes, proteins, metabolites or RNAs). Huge biological networks have emerged, where nodes correspond to these entities and edges between them model their relations. Protein-protein interaction networks, for instance, show the physical interactions of proteins in an organism. The comparison of such networks promises additional insights into protein and cell function as well as knowledge transfer across species. Several computational approaches have been developed previously to solve the network alignment (NA) problem, but only a few concentrate on the usability of the implemented tools for the evaluation of protein-protein interactions by the end users (biologists and medical researchers). RESULTS: We have created CytoGEDEVO, a Cytoscape app for visual and user-assisted NA. It extends the previous GEDEVO methodology for global pairwise NAs with new graphical and functional features. Our main focus was on the usability, even by non-programmers and the interpretability of the NA results with Cytoscape. AVAILABILITY AND IMPLEMENTATION: CytoGEDEVO is publicly available from the Cytoscape app store at http://apps.cytoscape.org/apps/cytogedevo In addition, we provide stand-alone command line executables, source code, documentation and step-by-step user instructions at http://cytogedevo.compbio.sdu.dk CONTACT: malek@tugraz.at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26669931 TI - Fifteen years after To Err is Human: a success story to learn from. PMID- 26669932 TI - The case for routine goals-of-care documentation. PMID- 26669933 TI - Response to: 'Improving the care of patients with a hip fracture: a quality improvement report' by Hawkes et al. PMID- 26669934 TI - Spatial learning and neurogenesis: Effects of cessation of wheel running and survival of novel neurons by engagement in cognitive tasks. AB - Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal-dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No-EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM-HD) or in a visible platform searching task, independent on hippocampal function (MWM-NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM-HD working memory task substantially increased survival of novel neurons, exposure to the MWM-NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. (c) 2015 Wiley Periodicals, Inc. PMID- 26669935 TI - Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study. AB - The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups. PMID- 26669937 TI - Dynamic distributions of tumor necrosis factor-alpha and its receptors in the red nucleus of rats with spared nerve injury. AB - Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain, and its effect is transmitted through TNF-alpha receptor (TNFR) subtypes 1 and 2. Here, the dynamic distributions of TNF-alpha and TNFRs in the RN of rats with spared nerve injury (SNI) were investigated. Western blot analysis and immunofluorescence staining indicated that TNF-alpha was hardly expressed in the RN of normal rats but significantly increased at 1 week and peaked at 2 weeks after SNI. Neurons and oligodendrocytes showed TNF-alpha expression at both 1 week and 2 weeks after SNI, while astrocytes and microglia produced TNF-alpha later than neurons and oligodendrocytes starting at 2 weeks after SNI. TNFR1 was constitutively expressed in the RN of normal rats and significantly enhanced at 2 weeks but not 1 week after SNI; it was mainly localized in neurons, oligodendrocytes and microglia. Astrocytes were not immunopositive for TNFR1 under normal conditions and at 1 week after injury, but small amounts of astrocytes showed TNFR1 expression at 2 weeks after SNI. A low level of TNFR2 was expressed in the RN of normal rats, but it was significantly increased at 1 week and 2 weeks after SNI and localized in neurons and all three types of glia. These findings suggest that neurons and three types of glia in the RN all contribute to TNF-alpha production and participate in the initiation and/or maintenance of neuropathic pain induced by SNI. TNF-alpha exerts its effects in different types of cells maybe through different receptors, TNFR1 and/or TNFR2, in the different stages of neuropathic pain. PMID- 26669936 TI - Bacterial Ghosts of Escherichia coli Drive Efficient Maturation of Bovine Monocyte-Derived Dendritic Cells. AB - Bacterial ghosts (BGs) are empty cell envelopes derived from Gram-negative bacteria. They not only represent a potential platform for development of novel vaccines but also provide a tool for efficient adjuvant and antigen delivery system. In the present study, we investigated the interaction between BGs of Escherichia coli (E. coli) and bovine monocyte-derived dendritic cells (MoDCs). MoDCs are highly potent antigen-presenting cells and have the potential to act as a powerful tool for manipulating the immune system. We generated bovine MoDCs in vitro from blood monocytes using E. coli expressed bovine GM-CSF and IL-4 cytokines. These MoDCs displayed typical morphology and functions similar to DCs. We further investigated the E. coli BGs to induce maturation of bovine MoDCs in comparison to E. coli lipopolysaccharide (LPS). We observed the maturation marker molecules such as MHC-II, CD80 and CD86 were induced early and at higher levels in BG stimulated MoDCs as compared to the LPS stimulated MoDCs. BG mediated stimulation induced significantly higher levels of cytokine expression in bovine MoDCs than LPS. Both pro-inflammatory (IL-12 and TNF-alpha) and anti-inflammatory (IL-10) cytokines were induced in MoDCs after BGs stimulation. We further analysed the effects of BGs on the bovine MoDCs in an allogenic mixed lymphocyte reaction (MLR). We found the BG-treated bovine MoDCs had significantly (p<0.05) higher capacity to stimulate allogenic T cell proliferation in MLR as compared to the LPS. Taken together, these findings demonstrate the E. coli BGs induce a strong activation and maturation of bovine MoDCs. PMID- 26669941 TI - Liver X receptor-alpha and miR-130a-3p regulate expression of sphingosine 1 phosphate receptor 2 in human umbilical vein endothelial cells. AB - Recent studies have shown that activation of liver X receptors (LXRs) attenuates the development of atherosclerosis, not only by regulating lipid metabolism but also by suppressing inflammatory signaling. Sphingosine 1-phosphate receptor 2 (S1PR2), an important inflammatory gene product, plays a role in the development of various inflammatory diseases. It was proposed that S1PR2 might be regulated by LXR-alpha. In the present study, the effect of LXR-alpha on tumor necrosis factor-alpha (TNF-alpha)-induced S1PR2 expression in human umbilical vein endothelial cells (HUVECs) was investigated and the underlying mechanism was explored. The results demonstrated that TNF-alpha led to an increase in S1PR2 expression and triggered a downregulation of LXR-alpha expression in HUVECs as well. Downregulation of LXR-alpha with specific small interfering RNA (siRNA) remarkably enhanced the primary as well as TNF-alpha-induced expression of S1PR2 in HUVECs. Activation of LXR-alpha by agonist GW3965 inhibited both primary and TNF-alpha-induced S1PR2 expression. GW3965 also attenuated S1PR2-induced endothelial barrier dysfunction. The data further showed that TNF-alpha induced a significant decrease in miR-130a-3p expression. Overexpression of miR-130a-3p with mimic product reduced S1PR2 protein expression, and inhibition of miR-130a 3p by specific inhibitor resulted in an increase in S1PR2 protein expression. Furthermore, activation of LXRs with agonist enhanced the expression of miR-130a 3p, and knockdown of LXR-alpha by siRNA suppressed miR-130a-3p expression. These results suggest that LXR-alpha might downregulate S1PR2 expression via miR-130a 3p in quiescent HUVECs. Stimulation of TNF-alpha attenuates the activity of LXR alpha and results in enhanced S1PR2 expression. PMID- 26669942 TI - Hospital length of stay and all-cause 30-day readmissions among high-risk Medicaid beneficiaries. AB - This study examined the association between index hospitalization characteristics and the risk of all-cause 30-day readmission among high-risk Medicaid beneficiaries using multilevel analyses. A retrospective cohort with a baseline and a follow-up period was used. The study population consisted of Medicaid beneficiaries (21-64 years old) with selected chronic conditions, continuous fee for-service enrollment through the observation period, and at least 1 inpatient encounter during the follow-up period (N = 15,806). The outcome of 30-day readmission was measured using inpatient admissions within 30-days from the discharge date of the first observed hospitalization. Key independent variables included length of stay, reason for admission, and month of index hospitalization (seasonality). Multilevel logistic regression that accounted for beneficiaries nested within counties was used to examine this association, after controlling for patient-level and county-level characteristics. In this study population, 16.7% had all-cause 30-day readmissions. Adults with greater lengths of stay during the index hospitalization were more likely to have 30-day readmissions (adjusted odds ratio [AOR]: 1.03, 95% confidence interval [CI]: 1.02-1.04). Adults who were hospitalized for cardiovascular conditions (AOR: 1.20, 95% CI: 1.08-1.33), diabetes (AOR: 1.23, 95% CI: 1.10-1.39), cancer (AOR: 1.55, 95% CI: 1.26-1.90), and mental health conditions (AOR: 2.17, 95% CI: 1.98-2.38) were more likely to have 30-day readmissions compared to those without these conditions. PMID- 26669943 TI - Strong Metal-Support Interactions between Gold Nanoparticles and Nonoxides. AB - The strong metal-support interaction (SMSI) is of great importance for supported catalysts in heterogeneous catalysis. We report the first example of SMSI between Au nanoparticles (NPs) and hydroxyapatite (HAP), a nonoxide. The reversible encapsulation of Au NPs by HAP support, electron transfer, and changes in CO adsorption are identical to the classic SMSI except that the SMSI of Au/HAP occurred under oxidative condition; the opposite condition for the classical SMSI. The SMSI of Au/HAP not only enhanced the sintering resistance of Au NPs upon calcination but also improved their selectivity and reusability in liquid phase reaction. It was found that the SMSI between Au and HAP is general and could be extended to other phosphate-supported Au systems such as Au/LaPO4. This new discovery may open a new way to design and develop highly stable supported Au catalysts with controllable activity and selectivity. PMID- 26669944 TI - Plantar cooling does not affect standing balance: A systematic review and meta analysis. AB - The purpose of this systematic review with meta-analysis was to critically appraise and synthesize the literature to determine if cooling the plantar surface of the foot is an effective method of inducing postural control alterations in healthy individuals. Specific variables that were evaluated within the meta-analysis included (1) the duration of the plantar cooling intervention, (2) the stance type during postural control assessment, and (3) the role of visual input. A computerized search of four electronic databases from inception to March 2015 was performed to identify studies which examined the effects of plantar cooling on postural control in healthy individuals. A critical appraisal of the methodological quality of the included studies was performed using an appraisal criteria instrument previously used for assessing biomechanics studies. The literature search yielded 88 references of which 7 were deemed relevant and included in the systematic review and meta-analysis. A single, overall random effects model meta-analysis of all study variables were performed; as well as, separate meta-analyses for each study variable. Across the 7 studies, the overall effect was 0.028 (95% CI=-0.177, 0.234; p=0.78) indicating that cooling the plantar surface had a very small effect on postural control. Similar results were obtained when data were examined based on study quality, plantar cooling intervention duration, stance type during postural control assessment, and the presence of visual input. Therefore, cooling the plantar surface of the foot had a very weak, non-significant effect on standing balance despite the anesthetic effects identified in each study. PMID- 26669945 TI - Repeatability of a 3D multi-segment foot model during anterior and lateral step down tests. AB - The aim of the present study was to analyse the reproducibility of the Oxford Foot Model (OFM) when used with healthy adults during two clinical tests, i.e., the Anterior Step Down Test (SDA) and the Lateral Step Down Test (SDL). Five healthy participants (one male and four females, 10 limbs in total) with a mean age of 22.2 (19-30) years were assessed in four sessions of tests conducted at intervals of one week. Two independent examiners performed two of the sessions of each of the tests. For each session (intra-day), nine repetitions of each clinical test (SDA and SDL) were performed. After an interval of three hours, the data were collected again. The tests were conducted again after an interval of one week using the same experimental conditions. The intra- and inter-session repeatabilities of the ranges of motion of the feet were determined according to the standard error of measurement (SEM) for each examiner and for the differences between the examiners. The repeatabilities of the results were high for both of the conducted tests. The SEM results were as follows: 0.47-1.94 degrees for the intra-examiner assessment (SDA), 0.55-2.01 degrees for the inter-examiner comparison (SDA), 0.44-2.43 degrees for the intra-examiner assessment (SDL), and 0.54-1.89 degrees for the inter-examiner comparison (SDL). The OFM model was shown to be reproducible in terms of assessing the range of motion of healthy adults during functional tests (SDA and SDL). PMID- 26669946 TI - Using gait parameters to detect fatigue and responses to ice slurry during prolonged load carriage. AB - This study examined (1) if changes in gait characteristics could indicate the exertional heat stress experienced during prolonged load carriage, and (2) if gait characteristics were responsive to a heat mitigation strategy. In an environmental chamber replicating tropical climatic conditions (ambient temperature 32 degrees C, 70% relative humidity), 16 males aged 21.8 (1.2) years performed two trials of a work-rest cycle protocol consisting two bouts of 4-km treadmill walks with 30-kg load at 5.3km/h separated by a 15-min rest period. Ice slurry (ICE) or room temperature water (29 degrees C) as a control (CON) was provided in 200-ml aliquots. The fluids were given 10min before the start, at the 15(th) and 30(th) min of each work cycle, and during each rest period. Spatio temporal gait characteristics were obtained at the start and end of each work rest cycle using a floor-based photocell system (OptoGait) and a high-speed video camera at 120Hz. Repeated-measure analysis of variance (trial*time) showed that with time, step width decreased (p=.024) while percent crossover steps increased (p=.008) from the 40(th) min onwards. Reduced stance time variability (-11.1%, p=.029) step width variability (-8.2%, p=.001), and percent crossover step ( 18.5%, p=.010) were observed in ICE compared with CON. No differences in step length and most temporal variables were found. In conclusion, changes in frontal plane gait characteristics may indicate exertional heat stress during prolonged load carriage, and some of these changes may be mitigated with ice slurry ingestion. PMID- 26669947 TI - Rectus femoris transfer surgery affects balance recovery in children with cerebral palsy: A computer simulation study. AB - Stiff-knee gait is a troublesome movement disorder among children with cerebral palsy (CP), where peak swing phase knee flexion is diminished due to over activity of the rectus femoris muscle. A common treatment for stiff-knee gait, rectus femoris transfer surgery, moves the muscle's distal tendon from the patella to the sartorius insertion on the tibia. As a biarticular muscle, rectus femoris may play a role in motor control and have unrecognized benefits for maintaining balance. We used musculoskeletal modeling, neuromuscular control, and forward dynamic simulation to investigate the role of rectus femoris tendon transfer surgery on balance recovery after support-surface perturbations for children with CP adopting two different crouched postures. We combined both high level supraspinal and low-level spinal signals to generate 92 muscle excitations for tracking experimental whole body center of mass positions and velocities. Stability during balance recovery was evaluated by the minimum distance between the extrapolated center of mass and base of support boundary (bmin) and the minimum time to reach the boundary (TtBmin). The balance recovery of pre-surgical simulations (bmin=2.3+1.1cm, TtBmin=0.2+0.1s) were different (p=0.02), on average, than post-surgical simulations (bmin=-4.9+11.4cm, TtBmin=-0.1+0.3s) of rectus femoris transfers. The moderate crouch simulations (bmin=2.4+0.4cm, TtBmin=0.2+0.03s) were more stable than the mild crouch simulations (bmin=1.2+0.3cm, TtBmin=0.1+0.02s) following anterior translations of the support surface. These findings suggest that tendon transfer of rectus femoris affects balance recovery in children with CP. PMID- 26669948 TI - Effects of adiposity on postural control and cognition. AB - In the U.S., it is estimated that over one-third of adults are obese (Body Mass Index (BMI)>30kg/m(2)). Previous studies suggest that obesity may be associated with deficits in cognitive performance and postural control. Increased BMI may challenge cognitive and postural performance in a variety of populations; however, most relevant studies have classified participants based on BMI values, which cannot be used to accurately assess the effects of adiposity on cognitive performance and postural control. The objective of the current study was to examine motor and cognitive responses for overweight and obese adults compared to normal weight individuals by using both BMI and adiposity measures. Ten normal weight (BMI=18-24.9kg/m(2)), ten overweight (BMI=25-29.9kg/m(2)), and ten obese (BMI=30-40kg/m(2)) adults were evaluated (age: 24+/-4 years). Participants were classified into three groups based on BMI values at the onset of the study, prior to body composition analysis. Participants performed (1) working memory task while maintaining upright stance, and (2) a battery of sensorimotor evaluations. Working memory reaction times, response accuracy, center-of-pressure (COP) path length, velocity, migration area, time to boundary values in anterior-posterior direction, and ankle-hip strategy-scores were calculated to evaluate cognitive motor performance. No significant deficits in working memory performance were observed. Overall, measures of motor function deteriorated as BMI and body fat percentage increased. The relationship between deteriorating postural performance indices and body fat percentage were greater than those found between BMI and postural performance indices. PMID- 26669949 TI - Do characteristics of a stationary obstacle lead to adjustments in obstacle stepping strategies? AB - Navigating cluttered and complex environments increases the risk of falling. To decrease this risk, it is important to understand the influence of obstacle visual cues on stepping parameters, however the specific obstacle characteristics that have the greatest influence on avoidance strategies is still under debate. The purpose of the current work is to provide further insight on the relationship between obstacle appearance in the environment and modulation of stepping parameters. Healthy young adults (N=8) first stepped over an obstacle with one visible top edge ("floating"; 8 trials) followed by trials where experimenters randomly altered the location of a ground reference object to one of 7 different positions (8 trials per location), which ranged from 6cm in front of, directly under, or up to 6cm behind the floating obstacle (at 2cm intervals). Mean take off and landing distance as well as minimum foot clearance values were unchanged across different positions of the ground reference object; a consistent stepping trajectory was observed for all experimental conditions. Contrary to our hypotheses, results of this study indicate that ground based visual cues are not essential for the planning of stepping and clearance strategies. The simultaneous presentation of both floating and ground based objects may have provided critical information that lead to the adoption of a consistent strategy for clearing the top edge of the obstacle. The invariant foot placement observed here may be an appropriate stepping strategy for young adults, however this may not be the case across the lifespan or in special populations. PMID- 26669950 TI - Validity and reliability of the activPAL3 for measuring posture and stepping in adults and young people. AB - Characterisation of free-living physical activity requires the use of validated and reliable monitors. This study reports an evaluation of the validity and reliability of the activPAL3 monitor for the detection of posture and stepping in both adults and young people. Twenty adults (median 27.6y; IQR22.6y) and 8 young people (12.0y; IQR4.1y) performed standardised activities and activities of daily living (ADL) incorporating sedentary, upright and stepping activity. Agreement, specificity and positive predictive value were calculated between activPAL3 outcomes and the gold-standard of video observation. Inter-device reliability was calculated between 4 monitors. Sedentary and upright times for standardised activities were within +/-5% of video observation as was step count (excluding jogging) for both adults and young people. Jogging step detection accuracy reduced with increasing cadence >150stepsmin(-1). For ADLs, sensitivity to stepping was very low for adults (40.4%) but higher for young people (76.1%). Inter-device reliability was either good (ICC(1,1)>0.75) or excellent (ICC(1,1)>0.90) for all outcomes. An excellent level of detection of standardised postures was demonstrated by the activPAL3. Postures such as seat-perching, kneeling and crouching were misclassified when compared to video observation. The activPAL3 appeared to accurately detect 'purposeful' stepping during ADL, but detection of smaller stepping movements was poor. Small variations in outcomes between monitors indicated that differences in monitor placement or hardware may affect outcomes. In general, the detection of posture and purposeful stepping with the activPAL3 was excellent indicating that it is a suitable monitor for characterising free-living posture and purposeful stepping activity in healthy adults and young people. PMID- 26669951 TI - Effect of seat and table top slope on the biomechanical stress sustained by the musculo-skeletal system. AB - The purpose of this study was to assess the effect of table and seat slope on the biomechanical stress sustained by the musculo-skeletal system. Angular position of the head and trunk, and surface electromyography of eleven postural muscles were recorded while seated under different conditions of seat slope (0 degrees , 15 degrees forward) and table slope (0 degrees , 20 degrees backward). The specific stress sustained by C7-T1 joint was estimated with isometric torque calculation. The results showed that the backward sloping table was associated with a reduction of neck flexion and neck extensors EMG, contrasting with a concurrent overactivity of the deltoideus. The forward sloping chair induced an anterior pelvic tilt, but also a higher activity of the knee (vasti) and ankle (soleus) extensors. It was concluded that sloping chairs and tables favor a more erect posture of the spine, but entails an undesirable overactivity of upper and lower limbs muscles to prevent the body from sliding. PMID- 26669952 TI - Center of mass trajectories during turning in patients with Parkinson's disease with and without freezing of gait. AB - BACKGROUND: Despite the strong relationship between freezing of gait (FOG) and turning in Parkinson's disease (PD), few studies have addressed specific postural characteristics during turning that might contribute to freezing. METHODS: Thirty participants with PD (16 freezers, 14 non-freezers) (all tested OFF medication) and 14 healthy controls walked 5 meters and turned 180 degrees in a 3D gait laboratory. COM behavior was analyzed during four turning quadrants of 40 degrees between 10 degrees and 170 degrees pelvic rotation and during 40 degrees before actual FOG episodes. These pre-FOG segments were compared with similar turning sections in turns of freezers without FOG. Outcome parameters were turn time, COM distance, COM velocity, step width and the medial- and anterior COM position. RESULTS: Turn time was increased in freezers compared to non-freezers (p=.000). No differences were found regarding COM distance and velocity during turning quadrants between groups and between freezers' pre-FOG segments and similar turning segments without FOG. Medial COM deviation was reduced in PD patients compared to controls (p=.004), but no differences were found between freezers and non-freezers. In turns with freezing, turn time increased (p=.005) and step width decreased (p=.025) pre-FOG. Freezers also showed a less medial (p=.020) and more anterior (p=.016) COM position pre-FOG compared to turning sections without FOG. CONCLUSIONS: Our results revealed no subgroup differences in COM behavior during uninterrupted turning. However, we found a reduced medial deviation, a forward COM shift and a decreased step width in freezers just before FOG episodes. These abnormalities may play a causal role, as they could hamper stability and fluent weight shifting necessary for continued stepping during turning. PMID- 26669953 TI - Direction-specific impairment of stability limits and falls in children with developmental coordination disorder: Implications for rehabilitation. AB - Limit of stability (LOS) is an important yet under-examined postural control ability in children with developmental coordination disorder (DCD). This study aimed to (1) compare the LOS and fall frequencies of children with and without DCD, and (2) explore the relationships between LOS parameters and falls in the DCD population. Thirty primary school-aged children with DCD and twenty age- and sex-matched typically-developing children participated in the study. Postural control ability, specifically LOS in standing, was evaluated using the LOS test. Reaction time, movement velocity, maximum excursion, end point excursion, and directional control were then calculated. Self-reported fall incidents in the previous week were also documented. Multivariate analysis of variance results revealed that children with DCD had shorter LOS maximum excursion in the backward direction compared to the control group (p=0.003). This was associated with a higher number of falls in daily life (rho=-0.556, p=0.001). No significant between-groups differences were found in other LOS-derived outcomes (p>0.05). Children with DCD had direction-specific postural control impairment, specifically, diminished LOS in the backward direction. This is related to their falls in daily life. Therefore, improving LOS should be factored into rehabilitation treatment for children with DCD. PMID- 26669954 TI - Quantifying performance and effects of load carriage during a challenging balancing task using an array of wireless inertial sensors. AB - We utilize an array of wireless inertial measurement units (IMUs) to measure the movements of subjects (n=30) traversing an outdoor balance beam (zigzag and sloping) as quickly as possible both with and without load (20.5kg). Our objectives are: (1) to use IMU array data to calculate metrics that quantify performance (speed and stability) and (2) to investigate the effects of load on performance. We hypothesize that added load significantly decreases subject speed yet results in increased stability of subject movements. We propose and evaluate five performance metrics: (1) time to cross beam (less time=more speed), (2) percentage of total time spent in double support (more double support time=more stable), (3) stride duration (longer stride duration=more stable), (4) ratio of sacrum M-L to A-P acceleration (lower ratio=less lateral balance corrections=more stable), and (5) M-L torso range of motion (smaller range of motion=less balance corrections=more stable). We find that the total time to cross the beam increases with load (t=4.85, p<0.001). Stability metrics also change significantly with load, all indicating increased stability. In particular, double support time increases (t=6.04, p<0.001), stride duration increases (t=3.436, p=0.002), the ratio of sacrum acceleration RMS decreases (t=-5.56, p<0.001), and the M-L torso lean range of motion decreases (t=-2.82, p=0.009). Overall, the IMU array successfully measures subject movement and gait parameters that reveal the trade off between speed and stability in this highly dynamic balance task. PMID- 26669956 TI - The effect of Masai Barefoot Technology (MBT) footwear on lower limb biomechanics: A systematic review. AB - This systematic review evaluated the available evidence for the effects of Masai Barefoot Technology (MBT) footwear on lower limb biomechanics during gait. Electronic databases (MEDLINE, EMBASE, CINAHL, SPORTDiscus, and PubMed) were searched in January 2015. Methodological quality of included studies was evaluated using the Quality Index. Standardised mean differences and 95% confidence intervals were calculated, and meta-analysis was conducted where possible. 17 studies satisfied the inclusion criteria; 16 cross-sectional studies and one randomised control trial (RCT). Quality Index scores ranged from 7 to 12 (out of 15). All 17 studies investigated walking gait only. Evidence showed that MBT footwear caused asymptomatic individuals to walk with a shorter stride length, reduced peak hip flexion, increased peak knee extension, and reduced hip and knee range of motion throughout gait. All kinematic effects occurred in the sagittal plane. There was a trend towards a decrease in internal and external joint moments and power, except for the foot, where increases in force were observed. There were only a small number of changes to lower limb muscle amplitude and timing. No statistically significant effects were observed in symptomatic individuals with knee osteoarthritis or following total knee replacement, but there was an increase in cadence and a decrease in step length in individuals following tibiotalar arthrodesis. These findings suggest that MBT footwear does change lower limb biomechanics in both asymptomatic and symptomatic individuals during gait. However, further clinical trials need to be undertaken to determine whether these changes are therapeutically beneficial. PMID- 26669955 TI - Novel application of a Wii remote to measure spasticity with the pendulum test: Proof of concept. AB - BACKGROUND: The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the test, an electrogoniometer is typically used to measure the knee angular motion. The device is costly and difficult to set up such that the pendulum test is normally time consuming. OBJECTIVE: The goal of this study is to determine whether a Nintendo Wii remote can replace the electrogroniometer for reliable assessment of the angular motion of the knee in the pendulum test. METHODS: The pendulum test was performed in three control participants and 13 hemiplegic stroke patients using both a Wii remote and an electrogoniometer. The correlation coefficient and the Bland-Altman difference plot were used to compare the results obtained from the two devices. The Wilcoxon signed-rank test was used to compare the difference between hemiplegia-affected and nonaffected sides in the hemiplegic stroke patients. RESULTS: There was a fair to strong correlation between measurements from the Wii remote and the electrogoniometer (0.513=4 cm dilation). The primary measured outcome was the length of second stage of labor. RESULTS: Overall, 200 cases were analyzed. Demographic, obstetrical, and labor characteristics were similar between the groups. Neither adverse events nor maternal or neonatal side effects were observed. The mean lengths of the active and second stages of labor were comparable between the obstetric gel-treated and the control groups (157 versus 219 min and 48 versus 56 min, respectively). None of the women had grade III/IV perineal tears. Maternal and neonatal outcomes were not negatively influenced by using obstetric gel. No difference was found after sub-group analysis for spontaneous vaginal delivery. CONCLUSION: Dianatal(r) obstetric gel is safe in terms of maternal or neonatal use. Albeit a trend toward shorter labor stages using Dianatal(r) obstetric gel, no significant differences were noted among the groups. In order to further investigate the influence of the obstetric gel on labor stage interval, perineal integrity and maternal and neonatal outcomes, larger randomized clinical trials are needed to be carried out. PMID- 26669966 TI - Ars Moriendi: Coping with death in the Late Middle Ages. AB - OBJECTIVE: The Ars moriendi was a book written in the early 15th century with the goal of assisting friars in their work of helping the dying. The aim of our study was to review the current literature on the Ars Moriendi concerning the field of medicine, to analyze the psychological mechanisms for coping with death anxiety within Ars Moriendi, and to explore parallels between the strategies used in the medieval book and in contemporary literature about death and dying. METHOD: A review of literature using Pubmed, EMBASE, JSTOR, Project MUSE, and the New York Public Library was undertaken first. The primary source was then interpreted from a medical/psychological point of view. RESULTS: Seven articles were selected by literature review. These works comment on the importance of the Ars Moriendi in its historical context and explore the possibility of retrieving the principles of the text in contemporary society. The original text of Ars Moriendi, the primary source, presents death as a relief from the sufferings of earthly life and a gateway to eternal glory. According to the author, a good death implied the triumph over five demonic temptations in agonizing people: a lack of faith, despair, impatience, pride and greed. SIGNIFICANCE OF RESULTS: Analyzed from a modern psychiatric perspective, the Ars Moriendi offers descriptions of behavioral manifestations compatible with delirium, mood and anxiety disorders that characterize people with terminal illnesses. Moreover, we also explored parallels between the strategies used to cope with death anxiety in the Late Middle Ages and in contemporary society. PMID- 26669967 TI - Fast Oxidative Cyclooligomerization towards Low- and High-Symmetry Thiophene Macrocycles. AB - Macrocycles with quaterthiophene subunits were obtained by cyclooligomerization by direct oxidative coupling of unsubstituted dithiophene moieties. The rings were closed with high selectivity by an alpha,beta'-connection of the thiophenes as proven by NMR spectroscopy. The reaction of the precursor with terthiophene moieties yielded the symmetric alpha,alpha'-linked macrocycle in low yield together with various differently connected isomers. Blocking of the beta position of the half-rings yielded selectively the alpha,alpha'-linked macrocycle. Selected cyclothiophenes were investigated by scanning tunneling microscopy, which displayed the formation of highly ordered 2D crystalline monolayers. PMID- 26669968 TI - Engineering Escherichia coli for Conversion of Glucose to Medium-Chain omega Hydroxy Fatty Acids and alpha,omega-Dicarboxylic Acids. AB - In search of sustainable approaches to plastics production, many efforts have been made to engineer microbial conversions of renewable feedstock to short-chain (C2-C8) bifunctional polymer precursors (e.g., succinic acid, cadaverine, 1,4 butanediol). Less attention has been given to medium-chain (C12-C14) monomers such as omega-hydroxy fatty acids (omega-OHFAs) and alpha,omega-dicarboxylic acids (alpha,omega-DCAs), which are precursors to high performance polyesters and polyamides. Here we engineer a complete microbial conversion of glucose to C12 and C14 omega-OHFAs and alpha,omega-DCAs, with precise control of product chain length. Using an expanded bioinformatics approach, we screen a wide range of enzymes across phyla to identify combinations that yield complete conversion of intermediates to product alpha,omega-DCAs. Finally, through optimization of culture conditions, we enhance production titer of C12 alpha,omega-DCA to nearly 600 mg/L. Our results indicate potential for this microbial factory to enable commercially relevant, renewable production of C12 alpha,omega-DCA-a valuable precursor to the high-performance plastic, nylon-6,12. PMID- 26669969 TI - A simple multi-well stretching device to induce inflammatory responses of vascular endothelial cells. AB - We herein introduce a novel multi-well stretching device that is made of three polydimethylsiloxane layers, consisting of a top hole-punched layer, middle thin membrane, and bottom patterned layer. It is the first time that such a simple device has been used to supply axisymmetric and nonuniform strains to cells cultured on well bottoms that are stretchable. These mechanical stimuli can somewhat mimic the stretching at the bending sites of blood vessels, where the strains are complicated. In this device, nonuniform strain is given to cells through the deformation of a membrane from a flat surface to a spherical cap during the injection of a certain volume of water into the chamber between the middle membrane and bottom layer. EA.hy926 cells (a human umbilical vein endothelial cell line) were seeded on the well bottoms and exposed to axisymmetric strain under a 5, 10, 15, and 20% degree of deformation of the membrane. The cellular responses were characterized in terms of cell morphology, cell viability, and expression of inflammatory mRNAs and proteins. With increasing the degree of deformation, the cells exhibited an inclination toward detachment and apoptosis; meanwhile the expression of inflammatory mRNAs and proteins, such as MCP-1, IL-8, IL-6 and ICAM-1, showed a significant increment. The obtained results demonstrate that the inflammatory responses of EA.hy926 cells can be induced by increasing the magnitude of the strain. This simple device provides a useful tool for in vitro investigation of the inflammatory mechanisms related to vascular diseases. PMID- 26669970 TI - Escherichia coli induces platelet aggregation in an FcgammaRIIa-dependent manner. AB - BACKGROUND: The discovery of pathogen-recognition receptors such as Toll-like receptors on platelets has led to the emergence of the concept of platelets as important components of the host response to infection. Escherichia coli (E. coli)-mediated sepsis is a serious illness characterized by the occurrence of thrombocytopenia. Whereas there has been a wealth of research on platelet activation by Gram-positive bacteria, little is known about the mechanisms associated with Gram-negative bacteria-induced platelet activation with Gram negative bacteria. OBJECTIVES: To determine the mechanisms by which Gram-negative E. coli induces platelet aggregation. METHODS: Induction of platelet aggregation with E. coli strain O157:H7 was tested in platelet-rich plasma (PRP), washed platelets, and serum depleted of complement factors. Platelet inhibitors (against alphaII b beta3 , glycoprotein Ibalpha and FcgammaRIIa) were used. Platelet thromboxane synthesis was analyzed after E. coli stimulation. Cell binding assays were used to assess the ability of E. coli to support platelet adhesion. Trypsinization was used to determine the role of E. coli surface proteins. RESULTS AND CONCLUSION: E. coli-induced aggregation in PRP was donor-dependent. E. coli O157:H7 induced aggregation with a lag time of 6.9 +/- 1.3 min in an alphaII b beta3 -dependent and FcgammaRIIa-dependent manner. Furthermore, this interaction was enhanced by the presence of complement, and was dependent on thromboxane synthesis. These results show E. coli to be a potent inducer of platelet aggregation. PMID- 26669971 TI - Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3). PMID- 26669973 TI - In vivo targeting of leukemia stem cells by directing parthenolide-loaded nanoparticles to the bone marrow niche. PMID- 26669974 TI - Risk factors for and outcomes of patients with POEMS syndrome who experience progression after first-line treatment. AB - Although clinical improvement is almost universal with therapy in patients with POEMS (an acronym for polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and a variety of skin changes) syndrome, outcomes and management of patients who relapse or progress (R/P) after first-line treatment have not been described. We retrospectively identified 262 patients with POEMS syndrome treated at the Mayo Clinic from 1974 to 2014 and who had follow-up information. The 5 year progression-free survival (PFS) and overall survival (OS) was 58% and 78%, respectively. Median time to R/P was 42 months. Seventy-nine patients (30%) had an R/P, with 52 (19%) experiencing a symptomatic R/P. Eighteen patients relapsed with symptoms or signs that were not documented at diagnosis. Median times to vascular endothelial growth factor, hematologic, radiographic and clinical R/P were 35 months (range, 4-327 months), 72 months (range, 4-327 months), 51 months (range, 4-327 months) and 48 months (range, 6-311 months), respectively. On multivariate analyses, low albumin at diagnosis and failure to achieve a complete hematologic response to first-line therapy were independent risk factors for PFS. Thirty patients had documentation of a second R/P at a median of 26 months from diagnosis of the first R/P. An early R/P was a risk factor for death, but most patients with an R/P had salvageable disease. A majority of patients are still without R/P at 5 years from diagnosis. PMID- 26669975 TI - Gene signature combinations improve prognostic stratification of multiple myeloma patients. AB - Multiple myeloma (MM) is a plasma cell neoplasm with significant molecular heterogeneity. Gene expression profiling (GEP) has contributed significantly to our understanding of the underlying biology and has led to several prognostic gene signatures. However, the best way to apply these GEP signatures in clinical practice is unclear. In this study, we investigated the integration of proven prognostic signatures for improved patient risk stratification. Three publicly available MM GEP data sets that encompass newly diagnosed as well as relapsed patients were analyzed using standardized estimation of nine prognostic MM signature indices and simulations of signature index combinations. Cox regression analysis was used to assess the performance of simulated combination indices. Taking the average of multiple GEP signature indices was a simple but highly effective way of integrating multiple GEP signatures. Furthermore, although adding more signatures in general improved performance substantially, we identified a core signature combination, EMC92+HZDCD, as the top-performing prognostic signature combination across all data sets. In this study, we provided a rationale for gene signature integration and a practical strategy to choose an optimal risk score estimation in the presence of multiple prognostic signatures. PMID- 26669972 TI - Genetic factors influencing the risk of multiple myeloma bone disease. AB - A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for ~6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio=1.38, P=4.09 * 10(-9)) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 * 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM. PMID- 26669976 TI - A small molecule compound IMB-LA inhibits HIV-1 infection by preventing viral Vpu from antagonizing the host restriction factor BST-2. AB - Human BST-2 inhibits HIV-1 replication by tethering nascent virions to the cell surface. HIV-1 codes Vpu that counteracts BST-2 by down-regulating this restriction factor from the cell surface. This important function makes Vpu a potential therapeutic target. Yet, no agents have been reported to block Vpu from antagonizing BST-2. In this study, we report a small molecule compound IMB-LA that abrogates the function of Vpu and thereby strongly suppresses HIV-1 replication by sensitizing the virus to BST-2 restriction. Further studies revealed that IMB-LA specifically inhibits Vpu-mediated degradation of BST-2 and restores the expression of BST-2 at the cell surface. Although IMB-LA does not prevent Vpu from interacting with BST-2 or beta-TrCP2-containing ubiquitin E3 ligase, sorting of BST-2 into lysosomes in Vpu-expressing cells is blocked by IMB LA. Most importantly, HIV-1 release and infection is inhibited by IMB-LA only in BST-2-expressing cells. In summary, results herein demonstrated that IMB-LA could specifically inhibit the degradation of BST-2 induced by Vpu, and impair HIV-1 replication in a BST-2 dependent manner, suggesting the feasibility of utilizing small molecule compounds to disable the antagonist function of Vpu and thereby expose HIV-1 to the restriction by BST-2. PMID- 26669979 TI - Religious Involvement and Telomere Length in Women Family Caregivers. AB - Telomere length (TL) is an indicator of cellular aging associated with longevity and psychosocial stress. We examine here the relationship between religious involvement and TL in 251 stressed female family caregivers recruited into a 2 site study. Religious involvement, perceived stress, caregiver burden, depressive symptoms, and social support were measured and correlated with TL in whole blood leukocytes. Results indicated a U-shaped relationship between religiosity and TL. Those scoring in the lowest 10% on religiosity tended to have the longest telomeres (5743 bp +/- 367 vs. 5595 +/- 383, p = 0.069). However, among the 90% of caregivers who were at least somewhat religious, religiosity was significantly and positively related to TL after controlling for covariates (B = 1.74, SE = 0.82, p = 0.034). Whereas nonreligious caregivers have relatively long telomeres, we found a positive relationship between religiosity and TL among those who are at least somewhat religious. PMID- 26669978 TI - Severity of Needs Among Individuals With Severe Mental Disorders: Changes After a Five-Year Follow-Up. AB - This study aims to assess (1) changes in severity of needs among 204 individuals with severe mental disorders (SMD) at 5-year follow-up and (2) predictors of the overall change in severity of needs. Severity of needs in 26 areas was compared at three different times. A repeated mixed design ANOVA model was used to assess predictors of the overall change in severity. Over the 5-year period, the severity of needs decreased significantly in five areas and increased significantly in only one. Predictors of overall change in severity of needs were related mostly to clinical and healthcare service variables (e.g., schizophrenia, without substance abuse disorder, efficient social functioning, high amount and adequacy of help, and continuity of care). To better respond to needs, healthcare services should focus on more disadvantaged individuals with SMD and dual diagnosis, especially those who require basic education and help in securing food. PMID- 26669977 TI - Bodily distress syndrome: A new diagnosis for functional disorders in primary care? AB - BACKGROUND: Conceptualisation and classification of functional disorders appear highly inconsistent in the health-care system, particularly in primary care. Numerous terms and overlapping diagnostic criteria are prevalent of which many are considered stigmatising by general practitioners and patients. The lack of a clear concept challenges the general practitioner's decision-making when a diagnosis or a treatment approach must be selected for a patient with a functional disorder. This calls for improvements of the diagnostic categories. Intense debate has risen in connection with the release of the fifth version of the 'Diagnostic and Statistical Manual of Mental Disorders' and the current revision of the 'International Statistical Classification of Diseases and Related Health Problems'. We aim to discuss a new evidence based diagnostic proposal, bodily distress syndrome, which holds the potential to change our current approach to functional disorders in primary care. A special focus will be directed towards the validity and utility criteria recommended for diagnostic categorisation. DISCUSSION: A growing body of evidence suggests that the numerous diagnoses for functional disorders listed in the current classifications belong to one family of closely related disorders. We name the underlying phenomenon 'bodily distress'; it manifests as patterns of multiple and disturbing bodily sensations. Bodily distress syndrome is a diagnostic category with specific criteria covering this illness phenomenon. The category has been explored through empirical studies, which in combination provide a sound basis for determining a symptom profile, the diagnostic stability and the boundaries of the condition. However, as bodily distress syndrome embraces only the most common symptom patterns, patients with few but impairing symptoms are not captured. Furthermore, the current lack of treatment options may also influence the acceptance of the proposed diagnosis. Bodily distress syndrome is a diagnostic category with notable validity according to empirical studies. Nevertheless, knowledge is sparse on the utility in primary care. Future intervention studies should investigate the translation of bodily distress syndrome into clinical practice. A particular focus should be directed towards the acceptability among general practitioners and patients. Most importantly, it should be investigated whether the new category may provide the basis for better treatment and improved clinical outcome. PMID- 26669981 TI - Associations Between Negative and Positive Life Events and the Course of Depression: A Detailed Repeated-Assessments Study. AB - Although the effects of life events on the onset of depression are well documented, little is known regarding their effects on the course of symptoms in depressed persons. We prospectively examined the associations between negative and positive life events and the course of depressive symptomatology in depressed primary care patients. A total of 267 depressed patients were followed for 3 years using a repeated-assessments design consisting of 36 monthly assessments of the 9 Diagnostic and Statistical Manual of Mental Disorders depression symptoms and positive and negative life events. We examined whether the severity of depressive symptomatology changed directly after the occurrence of a life event. Negative events were not associated with short-term changes in depressive symptomatology. In contrast, positive events were followed by a significant decrease in depressive symptoms one and two months after their occurrence. These findings may translate into emphasis during treatment on engagement in activities that may increase the chance of positive life experiences. PMID- 26669980 TI - Decreased Self-Concept Clarity in People with Schizophrenia. AB - Disturbances in the perception of self are thought to be central to the development of psychosis. Self-concept clarity (SCC) is the extent to which one's beliefs about oneself are internally consistent, stable, and clear. Participants with schizophrenia (N = 54) and healthy controls (N = 32) completed the Me Not-Me Decision Task (MNMDT), in which they decided whether 60 adjectives (30 pairs of antonyms) did or did not describe themselves. SCC is conceptualized as the number of consistent responses. Participants also completed the Self-Concept Clarity Scale (SCCS). Compared to healthy controls, participants with schizophrenia scored lower on the MNMDT and SCCS, and scores were negatively correlated with positive and negative symptoms. In a simultaneous regression, SCCS scores were uniquely associated with positive symptoms, whereas MNMDT scores were uniquely associated with negative symptoms. This suggests that people with schizophrenia have decreased self-concept clarity that is related to positive and negative symptoms. PMID- 26669982 TI - Understanding Perceptions of Anxiety Disorders and Their Treatment. AB - Characterizing areas of limited knowledge about anxiety disorders and their treatment may help inform treatment dissemination efforts and public health programming. In a sample of 626 adults recruited via Amazon's Mechanical Turk, this study evaluated 1) perceptions of symptoms of anxiety disorders and depression, 2) perceived usefulness of coping approaches (i.e., professional and non-professional help), and 3) awareness of available resources. Results indicated that participants generally recognized that symptoms warranted professional help, and recognition was associated with self-efficacy for seeking mental health care, but not with participants' own symptoms. Furthermore, participants perceived psychotherapy to be the most useful coping approach. Of concern is the perception that symptoms are the result of personal weakness (particularly among male participants and for social anxiety disorder), as well as limited knowledge about publicly available resources. In all, results suggest that there are areas for growth regarding mental health literacy for anxiety disorders. PMID- 26669983 TI - Exploratory Factor Analysis of Diagnostic and Statistical Manual, 5th Edition, Criteria for Posttraumatic Stress Disorder. AB - One change to the posttraumatic stress disorder (PTSD) nomenclature highlighted in the Diagnostic and Statistical Manual, 5th Edition (DSM-5; American Psychiatric Association, 2013) is the conceptualization of PTSD as a diagnostic category with four distinct symptom clusters. This article presents exploratory factor analysis to test the structural validity of the DSM-5 conceptualization of PTSD via an online survey that included the PTSD Checklist-5. The study utilized a sample of 113 college students from a large Midwestern university and 177 Amazon Mechanical Turk users. Participants were primarily female, Caucasian, single, and heterosexual with an average age of 32 years. Approximately 30% to 35% of participants met diagnostic criteria for PTSD based on two different scoring criteria. Results of the exploratory factor analysis revealed five distinct symptom clusters. The implications for the classification of PTSD are discussed. PMID- 26669984 TI - Factor Structure of the PTSD Checklist for DSM-5: Relationships Among Symptom Clusters, Anger, and Impulsivity. AB - Scarce data are available regarding the dimensional structure of Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) posttraumatic stress disorder (PTSD) symptoms and how factors relate to external constructs. We evaluated six competing models of DSM-5 PTSD symptoms, including Anhedonia, Externalizing Behaviors, and Hybrid models, using confirmatory factor analyses in a sample of 412 trauma-exposed college students. We then examined whether PTSD symptom clusters were differentially related to measures of anger and impulsivity using Wald chi-square tests. The seven-factor Hybrid model was deemed optimal compared with the alternatives. All symptom clusters were associated with anger; the strongest association was between externalizing behaviors and anger (r = 0.54). All symptom clusters, except re-experiencing and avoidance, were associated with impulsivity, with the strongest association between externalizing behaviors and impulsivity (r = 0.49). A seven-factor Hybrid model provides superior fit to DSM-5 PTSD symptom data, with the externalizing behaviors factor being most strongly related to anger and impulsivity. PMID- 26669985 TI - The Mesmerist by Arthur Seldon. PMID- 26669986 TI - The 41-cent Postage Stamp of Linus Pauling. PMID- 26669987 TI - Dr. H. A. Stoughton's Fresh Laughing Gas. PMID- 26669988 TI - JM25-1, a Lidocaine Analog Combining Airway Relaxant and Antiinflammatory Properties: Implications for New Bronchospasm Therapy. AB - BACKGROUND: Inhaled lidocaine antagonized bronchospasm in animal models and patients, but adverse effects limited its efficacy. This study evaluated the antibronchospasm potential of the analog JM25-1, exploring in vitro mechanisms and translation to an animal model. METHODS: The effectiveness of JM25-1 was assessed in GH3 cells, rat tracheal rings, mouse lymphocytes, and human eosinophil systems in vitro, assessing changes in Na current, contraction, proliferation, and survival, respectively. Lung function and inflammatory changes were studied in ovalbumin-sensitized mice. RESULTS: The efficacy of JM25-1 was higher than lidocaine in inhibiting carbachol-induced and calcium-induced tracheal contractions (maximum effect inhibition at 1 mM [%]: 67 +/- 10 [JM25-1] vs. 41 +/- 11 [lidocaine] [P < 0.001] for carbachol; 100 +/- 3 [JM25-1] vs. 36 +/ 26 [lidocaine] [P < 0.001] for Ca; mean +/- SD; n = 9 each) but lower in Na current (50% inhibitory concentration = 151.5, n = 8 vs. 0.2 mM; n = 5; P < 0.001). JM25-1 also inhibited eosinophil survival (dead cells [%]: 65 +/- 6; n = 4; P < 0.001 at 1 mM) and lymphocyte proliferation (cells in phase S + G2 [%]: 94 +/- 10; n = 6; P < 0.001) at 0.6 mM. Aerosolized JM25-1 (1%) decreased lung eosinophil numbers from 13.2 +/- 2.4 to 1.7 +/- 0.7 * 10/MUm (n = 6; P < 0.001) and neutrophils from 1.9 +/- 0.4 to 0.2 +/- 0.1 * 10/MUm (n = 7; P < 0.001). Other parameters, including airway hyperreactivity, cytokines, mucus, and extracellular matrix deposition, were also sensitive to aerosolized JM25-1. CONCLUSION: These findings highlight the potential of JM25-1, emphasizing its putative value in drug development for clinical conditions where there is bronchospasm. PMID- 26669990 TI - Do We Have an Alternative to Transforaminal Injections to Provide Safe and Effective Lumbar Epidural Steroid Injections to Our Patients While Minimizing the Burden to the Healthcare System? PMID- 26669989 TI - Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging: Implications for Analgesic Drug Development. AB - BACKGROUND: Attrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor. METHODS: The authors assessed the utility of functional magnetic resonance imaging with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, for obtaining mechanism-based objective outcome measures that can differentiate an effective analgesic (gabapentin) from an ineffective analgesic (ibuprofen) and both from placebo. The authors used a double-blind, randomized phase I study design (N = 24) with single oral doses. RESULTS: Only gabapentin suppressed the secondary mechanical hyperalgesia-evoked neural response in a region of the brainstem's descending pain modulatory system (right nucleus cuneiformis) and left (contralateral) posterior insular cortex and secondary somatosensory cortex. Similarly, only gabapentin suppressed the resting state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex, which was plasma gabapentin level dependent. A power analysis showed that with 12 data sets, when using neural activity from the left posterior insula and right nucleus cuneiformis, a statistically significant difference between placebo and gabapentin was detected with probability >= 0.8. When using subjective pain ratings, this reduced to less than or equal to 0.6. CONCLUSIONS: Functional imaging with central sensitization can be used as a sensitive mechanism-based assay to guide go/no-go decisions on selecting analgesics effective in neuropathic pain in early human drug development. We also show analgesic modulation of neural activity by using resting-state functional connectivity, a less challenging paradigm that is ideally suited for patient studies because it requires no task or pain provocation. PMID- 26669991 TI - The Devil Is in the Details. PMID- 26669992 TI - Insufficient Clarity of Statement 6 in the Consensus Opinions to Prevent Neurologic Complications after Epidural Steroid Injections. PMID- 26669993 TI - In Reply. PMID- 26669994 TI - Developing Perioperative Physicians. PMID- 26669995 TI - Meta-analysis of High-frequency Oscillation in Acute Respiratory Distress Syndrome and Accuracy of Results. PMID- 26669996 TI - In Reply. PMID- 26670004 TI - ADVERSE Drug Events: Incidence & risk reduction across the care continuum. PMID- 26670006 TI - Thermal properties of molecular crystals through dispersion-corrected quasi harmonic ab initio calculations: the case of urea. AB - An ab initio quantum-mechanical theoretical framework is presented to compute the thermal properties of molecular crystals. The present strategy combines dispersion-corrected density-functional-theory (DFT-D), harmonic phonon dispersion, quasi-harmonic approximation to the lattice dynamics for thermal expansion and thermodynamic functions, and quasi-static approximation for anisotropic thermo-elasticity. The proposed scheme is shown to reliably describe thermal properties of the urea molecular crystal by a thorough comparison with experimental data. PMID- 26670005 TI - In vivo cellular imaging of various stress/response pathways using AAV following axonal injury in mice. AB - Glaucoma, a leading cause of blindness worldwide, is instigated by various factors, including axonal injury, which eventually leads to a progressive loss of retinal ganglion cells (RGCs). To study various pathways reportedly involved in the pathogenesis of RGC death caused by axonal injury, seven pathways were investigated. Pathway-specific fluorescent protein-coded reporters were each packaged into an adeno-associated virus (AAV). After producing axonal injury in the eye, injected with AAV to induce RGC death, the temporal activity of each stress-related pathway was monitored in vivo through the detection of fluorescent RGCs using confocal ophthalmoscopy. We identified the activation of ATF6 and MCP 1 pathways involved in endoplasmic reticulum stress and macrophage recruitment, respectively, as early markers of RGC stress that precede neuronal death. Conversely, inflammatory responses probed by NF-kappaB and cell-death-related pathway p53 were most prominent in the later phases, when RGC death was already ongoing. AAV-mediated delivery of stress/response reporters followed by in vivo cellular imaging is a powerful strategy to characterize the temporal aspects of complex molecular pathways involved in retinal diseases. The identification of promoter elements that are activated before the death of RGCs enables the development of pre-emptive gene therapy, exclusively targeting the early phases of diseased cells. PMID- 26670007 TI - Factors Affecting Adnexal Torsion Direction: A Retrospective Cohort Study. AB - AIMS: To investigate a trend for adnexal torsion direction and factors that may be associated with direction. METHODS: We retrospectively reviewed the medical files of all women who underwent exploratory laparoscopy for suspected ovarian torsion in our center from August 2010 to December 2012. RESULTS: Fifty-five women had laparoscopically proven torsion. Medial rotation, defined as clockwise rotation of the left adnexa or counterclockwise rotation of the right adnexa, with the proximal (lateral) segment of the infundibulopelvic ligament serving as the referral point was noted in most cases (n = 47, 85.5%). There was no statistically significant difference between the medial and lateral rotation groups. However, the proportion of pregnant women and mean parity were significantly higher in the lateral compared to the medial rotation group: 62.5 vs. 19.1%, p = 0.009 and 1.1 +/- 1.2 vs. 0.1 +/- 0.4, p < 0.001. Medial torsion was present in 64.3% of pregnant women vs. 92.7% of nonpregnant women, p = 0.009. CONCLUSION: The direction of ovarian or adnexal torsion is usually medially rotated, opposite to the psoas muscles and the great blood vessels on the same side. However, surgeons should be aware of an increased rate of lateral rotation among pregnant women. PMID- 26670008 TI - The principle and physical models of novel jetting dispenser with giant magnetostrictive and a magnifier. AB - In order to develop jetting technologies of glue in LED and microelectronics packaging, giant-magnetostrictive-material (GMM) is firstly applied to increase jetting response, and a new magnifying device including a lever and a flexible hinge is designed to improve jetting characteristics. Physical models of the jetting system are derived from the magnifying structure and working principle, which involves circuit model, electro-magneto-displacement model, dynamic model and fluid-solid coupling model. The system model is established by combining mathematical models with Matlab-Simulink. The effectiveness of the GMM-based dispenser is confirmed by simulation and experiments. The jetting frequency significantly increases to 250 Hz, and dynamic behaviors jetting needle are evaluated that the velocity and displacement of the jetting needle reaches to 320 mm*s-1 and 0.11 mm respectively. With the increasing of the filling pressure or the amplitude of the current, the dot size will become larger. The dot size and working frequency can be easily adjusted. PMID- 26670010 TI - Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland. AB - BACKGROUND: The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. METHODS: Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. RESULTS AND DISCUSSION: A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. CONCLUSION: The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines. PMID- 26670011 TI - Mechanisms of disease: Stopping traffic. PMID- 26670009 TI - Subsite-specific contributions of different aromatic residues in the active site architecture of glycoside hydrolase family 12. AB - The active site architecture of glycoside hydrolase (GH) is a contiguous subregion of the enzyme constituted by residues clustered in the three dimensional space, recognizing the monomeric unit of ligand through hydrogen bonds and hydrophobic interactions. Mutations of the key residues in the active site architecture of the GH12 family exerted different impacts on catalytic efficiency. Binding affinities between the aromatic amino acids and carbohydrate rings were quantitatively determined by isothermal titration calorimetry (ITC) and the quantum mechanical (QM) method, showing that the binding capacity order of Tyr>Trp>His (and Phe) was determined by their side-chain properties. The results also revealed that the binding constant of a certain residue remained unchanged when altering its location, while the catalytic efficiency changed dramatically. Increased binding affinity at a relatively distant subsite, such as the mutant of W7Y at the -4 subsite, resulted in a marked increase in the intermediate product of cellotetraose and enhanced the reactivity of endoglucanase by 144%; while tighter binding near the catalytic center, i.e. W22Y at the -2 subsite, enabled the enzyme to bind and hydrolyze smaller oligosaccharides. Clarification of the specific roles of the aromatics at different subsites may pave the way for a more rational design of GHs. PMID- 26670013 TI - Metabolism: Keeping insulin secretion in check. PMID- 26670018 TI - Towards a simple typology of international health partnerships. AB - BACKGROUND: International health partnerships are one approach to capacity building in health systems. The evidence base for institutional partnerships for health service development remains weak and evaluation of the process and outcomes of health partnerships is a priority. The variability of partnerships contributes to the challenge of understanding their effectiveness and a typology of partnerships could aid evaluation. We analysed the proposals for all of the partnerships that received funding from the Tropical Health and Education Trust in 2012-2013 to develop such a typology. METHODS: Our data consisted of 54 successful project proposals for health partnerships funded by THET in 2012-2013. A coding strategy was developed and modified through five rounds of coding, discussion, modification of the coding strategy and re-coding. The final coding strategy classified partnerships according to impact, approach and relationships between partners. RESULTS: All 54 (100 %) of the partnerships in our sample planned to deliver training and 30 (56 %) aimed to deliver infrastructure strengthening in addition to training. 24 (44 %) aimed to build generic skills and 30 (56 %) specialist skills. 33(61 %) of the partners based in low and middle income countries had a scope of influence at national or international level and 33 (61 %) partnerships were between partners with an equal scope of influence. We suggest that those partnerships that focus on infrastructure strengthening and the development of generic skills might have more sustainable impacts in situations of high health care worker mobility and 12/54 partnerships met these criteria. CONCLUSION: We classified partnerships by their impact (scope of influence of LMIC partner and focus on individual/organisational development); approach to health systems strengthening (training/infrastructure; generic/specialist) and relationships (relative scope of influence between partners; mode of delivery - with an NGO partner or not). This is a first step in generating questions about partnership effectiveness that may be answered through evaluation. PMID- 26670019 TI - EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Long Version). AB - The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version). PMID- 26670016 TI - The exon junction complex as a node of post-transcriptional networks. AB - The exon junction complex (EJC) is deposited onto mRNAs following splicing and adopts a unique structure, which can both stably bind to mRNAs and function as an anchor for diverse processing factors. Recent findings revealed that in addition to its established roles in nonsense-mediated mRNA decay, the EJC is involved in mRNA splicing, transport and translation. While structural studies have shed light on EJC assembly, transcriptome-wide analyses revealed differential EJC loading at spliced junctions. Thus, the EJC functions as a node of post transcriptional gene expression networks, the importance of which is being revealed by the discovery of increasing numbers of EJC-related disorders. PMID- 26670017 TI - Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation. AB - The bacterial CRISPR-Cas9 system has emerged as a multifunctional platform for sequence-specific regulation of gene expression. This Review describes the development of technologies based on nuclease-deactivated Cas9, termed dCas9, for RNA-guided genomic transcription regulation, both by repression through CRISPR interference (CRISPRi) and by activation through CRISPR activation (CRISPRa). We highlight different uses in diverse organisms, including bacterial and eukaryotic cells, and summarize current applications of harnessing CRISPR-dCas9 for multiplexed, inducible gene regulation, genome-wide screens and cell fate engineering. We also provide a perspective on future developments of the technology and its applications in biomedical research and clinical studies. PMID- 26670021 TI - [Guideline-oriented treatment of alcohol-related disorders]. AB - Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15% of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved.This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40% could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year. PMID- 26670020 TI - High Diversity of CTX-M Extended-Spectrum beta-Lactamases in Municipal Wastewater and Urban Wetlands. AB - The CTX-M-type extended-spectrum beta-lactamases (ESBLs) present a serious public health threat as they have become nearly ubiquitous among clinical gram-negative pathogens, particularly the enterobacteria. To aid in the understanding and eventual control of the spread of such resistance genes, we sought to determine the diversity of CTX-M ESBLs not among clinical isolates, but in the environment, where weaker and more diverse selective pressures may allow greater enzyme diversification. This was done by examining the CTX-M diversity in municipal wastewater and urban coastal wetlands in southern California, United States, by Sanger sequencing of polymerase chain reaction amplicons. Of the five known CTX-M phylogroups (1, 2, 8, 9, and 25), only genes from groups 1 and 2 were detected in both wastewater treatment plants (WWTPs), and group 1 genes were also detected in one of the two wetlands after a winter rain. The highest relative abundance of blaCTX-M group 1 genes was in the sludge of one WWTP (2.1 * 10(-4) blaCTX-M copies/16S rRNA gene copy). Gene libraries revealed surprisingly high nucleotide sequence diversity, with 157 new variants not found in GenBank, representing 99 novel amino acid sequences. Our results indicate that the resistomes of WWTPs and urban wetlands contain diverse blaCTX-M ESBLs, which may constitute a mobile reservoir of clinically relevant resistance genes. PMID- 26670022 TI - [S3 guidelines on alcohol and tobacco-related disorders]. PMID- 26670023 TI - Assessment of Growth Factors Secreted by Human Breastmilk Mesenchymal Stem Cells. AB - INTRODUCTION: Human breastmilk is a dynamic, multifaceted biological fluid containing nutrients, bioactive substances, and growth factors. It is effective in supporting growth and development of an infant. As breastmilk has been found to possess mesenchymal stem cells, the importance of the components of breastmilk and their physiological roles is increasing day by day. The present study was intended to identify the secretions of growth factors, mainly vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), from human breastmilk mesenchymal stem cells under basal conditions of in vitro cell culture using synthetic media and human cord serum. MATERIALS AND METHODS: The growth factors were analyzed with the enzyme-linked immunosorbent assay technique. RESULTS: The cultured mesenchymal stem cells of breastmilk without serum revealed significant differences in secretions of the VEGF and HGF growth factors (8.55 +/ 2.26402 pg/mL and 230.8 +/- 45.9861 pg/mL, respectively) compared with mesenchymal stem cells of breastmilk with serum (21.31 +/- 4.69 pg/mL and 2,404.42 +/- 481.593 pg/mL, respectively). CONCLUSIONS: Results obtained from our study demonstrate that both VEGF and HGF are secreted in vitro by human breastmilk mesenchymal stem cells. The roles of VEGF and HGF in surfactant secretion, pulmonary maturation, and neonatal maturity have been well established. Thus, we emphasize that breastmilk-derived MSCs could be a potent therapeutic source in treating neonatal diseases. Besides, due to its immense potency, the study also emphasizes the importance of breastfeeding, which is promoted by organizations like the World Heatlh Organization and UNICEF. PMID- 26670024 TI - Adjunct cyclosporine therapy for refractory Kawasaki disease in a very young infant. AB - Herein we describe the case of a 6-week-old boy who developed complete Kawasaki disease (KD). The cytokine profile and activation of monocytes and subsequent T cells matched the typical feature of refractory KD. The patient received a total of three courses of i.v. immunoglobulin (IVIG), but did not achieve clinical relief. Adjunctive therapy with oral cyclosporine A (CsA) led to prompt defervescence. This was continued for 7 days without serious adverse events. Coronary artery dilatations regressed within 3 months of follow up. KD infants <3 months of age are at higher risk of coronary artery aneurysm than the older ones. To our knowledge, oral CsA treatment has not been reported in such young infants with KD. The diagnosis and treatment of very young infants with KD are challenging. Adjunctive use of CsA in IVIG treatment could be effective for refractory KD in infants <3 months of age. PMID- 26670025 TI - Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units. AB - This study assessed the rate of errors in intravenous medicine preparation at bedside in neonatal intensive care units versus preparation error rate in a hospital pharmacy service before and after several strategies were implemented. We performed a prospective observational study during 2013-2015. Ten Spanish neonatal intensive care units and one hospital pharmacy service participated in the study. Two types of preparation errors were considered, calculation errors and accuracy errors. The study was carried out over three consecutive phases: (1) pre-intervention phase, when medicine preparation samples were collected from neonatal intensive care units and hospital pharmacy service according to their normal clinical practice; (2) intervention phase, when protocol standardisation and educational strategy took place; and (3) post-intervention phase, when new medicine samples were collected after strategy implementation. In neonatal intensive care units, 1.35 % of samples registered calculation errors in pre intervention phase; no calculation errors were registered in hospital pharmacy service samples. In post-intervention phase, no calculation errors were registered in either group. Accuracy error rate decreased both in neonatal intensive care units (54.7 vs 23 %) and hospital pharmacy service (38.3 vs 14.6 %). CONCLUSION: Calculation errors can disappear with good standardisation protocols. Decrease in accuracy error depends on good preparation technique and environmental factors. WHAT IS KNOWN: * Medication use is associated with a risk of errors and adverse events. Medication errors are more frequent and have more severe consequences in paediatric patients. * Lack of commercial drug formulations adapted to newborn infants makes medicine preparation process more prone to error. What is New: * Calculation errors are minimising using concentration standard protocols. Preparation rules are essential to ensure the accuracy process. * Environmental conditions affect the accuracy process. PMID- 26670026 TI - Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry. AB - The aim of this study was to characterize the phenotype and treatment of young patients (manifestation <30 years) with diabetes of mitochondrial origin (DMO), based on the German/Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry. Only 13 (0.02 %) of all patients with diabetes in this cohort were identified with DMO, mainly due to the Kearns-Sayre (n = 5), Pearson (n = 3), or mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 2). The onset of DMO (14.2, interquartile range (IQR) 7.1-16 years) was later than diabetes onset in individuals with T1D but earlier than in T2D. At manifestation, patients exhibited a mild elevation of blood glucose concentrations (251, IQR 178-299 mg/dl) without ketoacidosis. They had lower body mass index (BMI) values (-1.39 +/- 0.28 kg/m(2)) than peers with T1D or T2D (p < 0.0001) and higher triglycerides (211, IQR 134-574 mg/dl) than in T1D (p = 0.04) while there was a high rate of dyslipidemia (86 %). Insulin requirements (0.58, IQR 0.37-0.90 U/kg/d) were between T1D and T2D while glucometabolic control (glycated hemoglobin A1c (HbA1c) 7.4 +/- 0.52 %) in DMO was comparable to age-matched T2D and stable over a 5-year follow-up. CONCLUSION: Primary mitochondrial disorders are a rare cause of juvenile diabetes and likely to be underdiagnosed. As there is clinical overlap with T1D and T2D, dyslipidemia and low body weight may help to identify further DMO cases. WHAT IS KNOWN: * In adults diabetes of mitochondrial origin (DMO) is a rare cause of non-autoimmune diabetes, affecting about 0.8 % of diabetes cases. * Common features are a maternal family history of diabetes, hearing loss and neurological abnormalities. What is New: * In our juvenile cohort 0.02 % of diabetes patients (age < 30 years) were affected by DMO, while Kearns Sayre, MELAS and Pearson syndrome were the most frequent entities. * Juvenile DMO patients exhibited dyslipidemia, higher triglycerides and a lower BMI than peers with T1D or T2D, while some patients also showed retinal changes. PMID- 26670027 TI - Characteristics of the menstrual cycle in 13-year-old Flemish girls and the impact of menstrual symptoms on social life. AB - This study aimed to investigate the characteristics of symptoms related to the menstrual cycle and their impact on social activities in young teenage girls. Between March and June 2009, all girls born in 1996 who were residents of eight regions in Flanders (Belgium) received a semi-structured questionnaire, including questions about the age of menarche, characteristics of the menstrual cycle, and its impact on social activities. Participants were 792 13-year-old girls (15.7 % of the target population). Out of 363 (47.2 % of participants) postmenarcheal girls, 41.6 % (95 % confidence interval (CI) 36.4-47.0 %) reported painful menstruations. The proportion of girls with painful menstrual periods decreased approximately 16 % with each year the age at menarche increased (relative risk (RR) = 0.84; 0.73-0.98; p < 0.05) and was positively correlated with the amount of blood loss (RR = 0.33; 0.16-0.67; p < 0.05 when little and 1.85; 1.49-2.31; p < 0.001 when abundant, compared to average). One in four (25.4 %) postmenarcheal girls indicated a negative impact of menstruation on social activities, but this proportion was significantly higher in girls who experienced menstruation as painful (41.3 %) compared to those who did not (14.2 %). CONCLUSION: Early menstrual complaints are common in young adolescent girls and the likelihood of pain increased significantly with lower menarcheal age. What is Known? * Menstrual cycle-related symptoms may negatively interfere with school absence and social activities. * Early menarche and severe dysmenorrhea are correlated with endometriosis. What is New? * In this large population-based study on the characteristics of the menstrual cycle in young teenage girls at or shortly after menarche, painful menstruation was highly prevalent (41.7 %), but related school absenteeism was low (3.2 %). The likelihood of pain increased significantly with lower menarcheal age. * The findings support the need for a systematic evaluation of the characteristics of the menstrual cycle shortly after menarche. PMID- 26670028 TI - Characterization of Cu(II) and Cd(II) resistance mechanisms in Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE-OCH and their potential application in the bioremediation of heavy metal-phenanthrene co-contaminated sites. AB - Soil that is co-contaminated with heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) is difficult to bioremediate due to the ability of toxic metals to inhibit PAH degradation by bacteria. We demonstrated the resistance mechanisms to Cu(II) and Cd(II) of two newly isolated strains of Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE-OCH and further tested their potential application in the bioremediation of HM-phenanthrene (PhA) co-contaminated sites. The PHE-SPH and PHE-OCH strains tolerated 4.63 and 4.34 mM Cu(II) and also showed tolerance to 0.48 and 1.52 mM Cd(II), respectively. Diverse resistance patterns were detected between the two strains. In PHE-OCH cells, the maximum accumulation of Cu(II) occurred in the cell wall, while the maximum accumulation was in the cytoplasm of PHE-SPH cells. This resulted in a sudden suppression of growth in PHE-OCH and a gradual inhibition in PHE-SPH as the concentration of Cu(II) increased. Organic acid production was markedly higher in PHE-OCH than in PHE SPH, which may also have a role in the resistance mechanisms, and contributes to the higher Cd(II) tolerance of PHE-OCH. The factors involved in the absorption of Cu(II) or Cd(II) in PHE-SPH and PHE-OCH were identified as proteins and carbohydrates by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, both strains showed the ability to efficiently degrade PhA and maintained this high degradation efficiency under HM stress. The high tolerance to HMs and the PhA degradation capacity make Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE OCH excellent candidate organisms for the bioremediation of HM-PhA co contaminated sites. PMID- 26670029 TI - Quantifying statistical relationships between commonly used in vitro models for estimating lead bioaccessibility. AB - Bioaccessibility to assess potential risks resulting from exposure to Pb contaminated soils is commonly estimated using various in vitro methods. However, existing in vitro methods yield different results depending on the composition of the extractant as well as the contaminated soils. For this reason, the relationships between the five commonly used in vitro methods, the Relative Bioavailability Leaching Procedure (RBALP), the unified BioAccessibility Research Group Europe (BARGE) method (UBM), the Solubility Bioaccessibility Research Consortium assay (SBRC), a Physiologically Based Extraction Test (PBET), and the in vitro Digestion Model (RIVM) were quantified statistically using 10 soils from long-term Pb-contaminated mining and smelter sites located in Western Australia and South Australia. For all 10 soils, the measured Pb bioaccessibility regarding all in vitro methods varied from 1.9 to 106% for gastric phase, which is higher than that for intestinal phase: 0.2 ~ 78.6%. The variations in Pb bioaccessibility depend on the in vitro models being used, suggesting that the method chosen for bioaccessibility assessment must be validated against in vivo studies prior to use for predicting risk. Regression studies between RBALP and SRBC, RBALP and RIVM (0.06) (0.06 g of soil in each tube, S:L ratios for gastric phase and intestinal phase are 1:375 and 1:958, respectively) showed that Pb bioaccessibility based on the three methods were comparable. Meanwhile, the slopes between RBALP and UBM, RBALP and RIVM (0.6) (0.6 g soil in each tube, S:L ratios for gastric phase and intestinal phase are 1:37.5 and 1:96, respectively) were 1.21 and 1.02, respectively. The findings presented in this study could help standardize in vitro bioaccessibility measurements and provide a scientific basis for further relating Pb bioavailability and soil properties. PMID- 26670030 TI - Water level fluctuations in a tropical reservoir: the impact of sediment drying, aquatic macrophyte dieback, and oxygen availability on phosphorus mobilization. AB - Reservoirs in semi-arid areas are subject to water level fluctuations (WLF) that alter biogeochemical processes in the sediment. We hypothesized that wet-dry cycles may cause internal eutrophication in such systems when they affect densely vegetated shallow areas. To assess the impact of WLF on phosphorus (P) mobilization and benthic P cycling of iron-rich sediments, we tested the effects of (i) sediment drying and rewetting, (ii) the impact of organic matter availability in the form of dried Brazilian Waterweed (Egeria densa), and (iii) alternating redox conditions in the surface water. In principle, drying led to increased P release after rewetting both in plant-free and in plant-amended sediments. Highest P mobilization was recorded in plant amendments under oxygen free conditions. After re-establishment of aerobic conditions, P concentrations in surface water decreased substantially owing to P retention by sediments. In desiccated and re-inundated sediments, P retention decreased by up to 30% compared to constantly inundated sediments. We showed that WLF may trigger biochemical interactions conducive to anaerobic P release. Thereby, E. densa showed high P release and even P uptake that was redox-controlled and superimposed sedimentary P cycling. Macrophytes play an important role in the uptake of P from the water but may be also a significant source of P in wet-dry cycles. We estimated a potential for the abrupt release of soluble reactive phosphorus (SRP) by E. densa of 0.09-0.13 g SRP per m(2) after each wet-dry cycle. Released SRP may exceed critical P limits for eutrophication, provoking usage restrictions. Our results have implications for management of reservoirs in semi-arid regions affected by WLF. PMID- 26670031 TI - Cytogenetic effects of three commercially formulated pesticides on somatic and germ cells of Allium cepa. AB - Cytological effects of Endosri-ES (endosulfan), Nuvan-NU (dichlorvos), and Kvistin-KS (carbendazim) were evaluated on mitotic and meiotic cells of Allium cepa. Test concentrations were chosen by calculating EC50 values of formulated ES, NU, and KS, which turned to be 60, 200, and 500 ppm (parts per million), respectively. Cytological studies were undertaken on root meristem cells of A. cepa using EC50, 1/2 * EC50, and 2 * EC50 of these pesticides for 24 and 48 h. Similarly, a meiotic study was conducted by applying the pesticides at the aforesaid concentrations from seedling to bud stage. A set of onion bulbs exposed to tap water was run parallel for negative control and maleic hydrazide (112.09 ppm) as positive control. During the study period, mitotic index (MI) decreased at all the pesticide concentrations compared to the negative control. Among various chromosomal aberrations, chromatin bridges, breaks, stickiness, laggard, vagrant chromosomes, fragments, C-mitosis, multipolarity, ring chromosome as well as micronuclei were observed in mitotic preparations. In contrast, meiotic aberrations revealed comparatively less frequency of chromosomal aberrations and the most frequent were lagging chromosome, stray bivalents, secondary association, chromatin bridge, disturbed anaphase, and stickiness. Comparative analysis of the pesticides showed that NU was highly toxic to plant cells than KS, while as ES showed intermediate effects between the two. Further, our study revealed that all the three pesticides produce genotoxic effects which can cause health risks to the human populations. Graphical Abstract ?. PMID- 26670032 TI - Role of angiotensin II in stem cell therapy of cardiac disease. AB - INTRODUCTION: The renin angiotensin system (RAS) is closely related to the cardiovascular system, body fluid regulation and homeostasis. MATERIALS AND METHODS: Despite common therapeutic methods, stem cell/progenitor cell therapy is daily increasing as a term of regenerative medicine. RAS and its pharmacological inhibitors are not only involved in physiological and pathological aspects of the cardiovascular system, but also affect the different stages of stem cell proliferation, differentiation and function, via interfering cell signaling pathways. RESULTS: This study reviews the new role of RAS, in particular Ang II distinct from other common roles, by considering its regulating impact on the different signaling pathways involved in the cardiac and endothelial tissue, as well as in stem cell transplantation. CONCLUSIONS: This review focuses on the impact of stem cell therapy on the cardiovascular system, the role of RAS in stem cell differentiation, and the role of RAS inhibition in cardiac stem cell growth and development. PMID- 26670033 TI - Persistent Organic Pollutants and Concern Over the Link with Insulin Resistance Related Metabolic Diseases. AB - Persistent organic pollutants (POPs) are mostly halogenated compounds tending to persist in the environment, enter into the food chain, and accumulate in fat mass of mammals due to their high lipophilicity. They include some organochlorine pesticides, polychlorinated biphenyls, brominated flame retardants and polycyclic aromatic hydrocarbons. Some of these chemicals were widely used in the past so that their residues can be detected in the human body, though their usage has been banned for years. POPs have been shown to perturb the health of biological systems in different ways evidenced by carcinogenicity and disrupting effects on endocrine, immune, and reproductive systems. There are many epidemiologic and experimental studies on the association of exposure to POPs with insulin resistance and related metabolic disorders like obesity, diabetes, and metabolic syndrome. Inflammation as a known mechanism accompanying insulin resistance has also been shown to arise in insulin target tissues exposed to POPs. This review addresses the breast milk concentration of POPs in different regions of the world, synthesizes the current information on the association of POPs with insulin resistance related metabolic disorders, and discusses the inflammation as an involved mechanism. Considering high prevalence of insulin resistance related metabolic diseases and their relation with POPs, much need is felt regarding international and regional programs to not only limit their production and usage but eliminate these persistent pollutants from the environment. PMID- 26670034 TI - Lead Toxicity, Antioxidant Defense and Environment. AB - Environmental and occupational exposure to a large number of chemicals occurs at various stages throughout human life. Many of these are devoid of toxicity, but some could pose a significant health risk, i.e. the exposure to environmental xenobiotic metals as lead, mercury (Sinicropi et al. 2010a; Carocci et al. 2014), cadmium, etc. In particular, lead has long been a widespread public concern (Basha and Reddy 2010). Lead is one of the earliest heavy metals discovered by men. Due to its unique properties, as low melting point, softness, malleability, ductility, and resistance to corrosion, men have used lead for the last 5000 years in a wide range of applications. PMID- 26670035 TI - Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM) in the Oil and Gas Industry: A Review. AB - Radiation is part of the natural environment: it is estimated that approximately 80 % of all human exposure comes from naturally occurring or background radiation. Certain extractive industries such as mining and oil logging have the potential to increase the risk of radiation exposure to the environment and humans by concentrating the quantities of naturally occurring radiation beyond normal background levels (Azeri-Chirag-Gunashli 2004). PMID- 26670036 TI - Post-earthquake recovery in Nepal. PMID- 26670037 TI - Characterization of a Cryptic and Intriguing Low Molecular Weight Plasmid. AB - The complete nucleotide sequence of cryptic plasmid pVCM04 isolated from Salmonella enterica serovar Enteritidis was determined and analyzed. pVCM04 contains 3853 bp with 53.6 % GC content and has twelve ORFs with more than 50 amino acids. Five of these sequences showed homology with replication and mobilization proteins. ORF1 and ORF2 showed homology with replication proteins, while ORFs 3-5 showed homology with mobilization proteins. The pVCM04 possesses a region associated with the theta-type replication mechanism. BLASTn search analysis revealed unexpectedly no similarity with sequences deposited in GenBank. The nucleotide sequence of pVCM04 can be divided into two arms: the region between nucleotides 552-1774 (encoding RepA and RepB) and the region between nucleotides 1775-3853 (encoding MobA, MobB and MobC). Codon bias pattern is distinct between mobA and repA, so the program Modeltest was used to select the best evolutionary model to study these genes. The result of ModelTest (model GTR+G for mobA and model HKY+G for repA) suggests that these genes would be subject to different selective pressures. Considering the differences in the codon usage, the selection of two different evolutionary models, and the absence of plasmids with homology to pVCM04 in GenBank, we believe that pVCM04 is a chimeric molecule and represents a new plasmid lineage. PMID- 26670038 TI - Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases. AB - PURPOSE: To analyze the clinical characteristics of blood culture-negative endocarditis (BCNE) and how it compares to those of blood culture-positive endocarditis (BCPE) cases and show how molecular tools helped establish the etiology in BCNE. METHODS: Adult patients with definite infective endocarditis (IE) and having valve surgery were included. Valves were studied by polymerase chain reaction (PCR). Statistical analysis compared BCNE and BCPE. RESULTS: One hundred and thirty-one patients were included; 53 (40 %) had BCNE. The mean age was 45 +/- 16 years; 33 (62 %) were male. BCNE was community-acquired in 41 (79 %). Most patients were referred from other hospitals (38, 73 %). Presentation was subacute in 34 (65 %), with fever in 47/53 (90 %) and a new regurgitant murmur in 34/42 (81 %). Native valves were affected in 74 %, mostly left-sided. All echocardiograms showed major criteria for IE. Antibiotics were used prior to BC collection in 31/42 (74 %). Definite histological diagnosis was established for 35/50 (70 %) valves. PCR showed oralis group streptococci in 21 (54 %), S. aureus in 3 (7.7 %), gallolyticus group streptococci in 2 (5.1 %), Coxiella burnetii in 1 (2.5 %) and Rhizobium sp. in 1 (2.5 %). In-hospital mortality was 9/53 (17 %). Fever (p = 0.06, OR 4.7, CI 0.91-24.38) and embolic complications (p = 0.003, OR 3.3, CI 1.55-6.82) were more frequent in BCPE cases, while new acute regurgitation (p = 0.05, OR 0.3, CI 0.098-0.996) and heart failure (p = 0.02, OR 0.3, CI 0.13-0.79) were less so. CONCLUSIONS: BCNE resulted mostly from prior antibiotics and was associated with severe hemodynamic compromise. Valve histopathology and PCR were useful in confirming the diagnosis and pointing to the etiology of BCNE. PMID- 26670039 TI - Conserved termini and adjacent variable region of Twortlikevirus Staphylococcus phages. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing cause of serious infection, both in the community and hospital settings. Despite sophisticated strategies and efforts, the antibiotic options for treating MRSA infection are narrowing because of the limited number of newly developed antimicrobials. Here, four newly-isolated MRSA-virulent phages, IME-SA1, IMESA2, IME-SA118 and IME-SA119, were sequenced and analyzed. Their genome termini were identified using our previously proposed "termini analysis theory". We provide evidence that remarkable conserved terminus sequences are found in IME SA1/2/118/119, and, moreover, are widespread throughout Twortlikevirus Staphylococcus phage G1 and K species. Results also suggested that each phage of the two species has conserved 5' terminus while the 3' terminus is variable. More importantly, a variable region with a specific pattern was found to be present near the conserved terminus of Twortlikevirus S. phage G1 species. The clone with the longest variable region had variable terminus lengths in successive generations, while the clones with the shortest variable region and with the average length variable region maintained the same terminal length as themselves during successive generations. IME-SA1 bacterial infection experiments showed that the variation is not derived from adaptation of the phage to different host strains. This is the first study of the conserved terminus and variable region of Twortlikevirus S. phages. PMID- 26670040 TI - Impact of pigeon pea biochar on cadmium mobility in soil and transfer rate to leafy vegetable spinach. AB - Introduction of heavy metals in the environment by various anthropogenic activities has become a potential treat to life. Among the heavy metals, cadmium (Cd) shows relatively high soil mobility and has high phyto-mammalian toxicity. Integration of soil remediation and ecosystem services, such as carbon sequestration in soils through organic amendments, may provide an attractive land management option for contaminated sites. The application of biochar in agriculture has recently received much attention globally due to its associated multiple benefits, particularly, long-term carbon storage in soil. However, the application of biochar from softwood crop residue for heavy metal immobilization, as an alternative to direct field application, has not received much attention. Hence, a pot experiment was conducted to study the effect of pigeon pea biochar on cadmium mobility in a soil-plant system in cadmium-spiked sandy loam soil. The biochar was prepared from pigeon pea stalk through a slow pyrolysis method at 300 degrees C. The experiment was designed with three levels of Cd (0, 5, and 10 mg Cd kg(-1) soil) and three levels of biochar (0, 2.5, and 5 g kg(-1) soil) using spinach as a test crop. The results indicate that with increasing levels of applied cadmium at 5 and 10 mg kg(-1) soil, the dry matter yield (DMY) of spinach leaf decreased by 9.84 and 18.29 %, respectively. However, application of biochar (at 2.5 and 5 g kg(-1) soil) significantly increased the dry matter yield of spinach leaf by 5.07 and 15.02 %, respectively, and root by 14.0 and 24.0 %, respectively, over the control. Organic carbon content in the post-harvest soil increased to 34.9 and 60.5 % due to the application of biochar 2.5 and 5 g kg(-1) soil, respectively. Further, there was a reduction in the diethylene triamine pentaacetic acid (DTPA)-extractable cadmium in the soil and in transfer coefficient values (soil to plant), as well as its concentrations in spinach leaf and root, indicating that cadmium mobility was decreased due to biochar application. This study shows that pigeon pea biochar has the potential to increase spinach yield and reduce cadmium mobility in contaminated sandy soil. PMID- 26670042 TI - Persistence and dissipation kinetics of chlorantraniliprole 0.4G in the soil of tropical sugarcane ecosystem. AB - Chlorantraniliprole 0.4 % GR has been in use for managing early shoot borer and top borer of sugarcane. Persistence and dissipation kinetics of granular formulation of chlorantraniliprole were studied in the soil of tropical sugarcane ecosystem by employing simple and sensitive analytical method. Limit of quantification of the method was 0.01 mg/kg and the recovery of chlorantraniliprole was in the range of 92.3-99.7 % with RSD of 1.14-3.0 %. The initial deposit of chlorantraniliprole in the soil was 0.513 and 1.031 mg/kg for the recommended (75 g a.i./ha) and double the recommended (150 g a.i./ha) doses, respectively. The residues were quantified up to 30 days after treatment irrespective of the doses applied. Half-life (t 1/2) was 6.60 and 6.73 days, respectively, for recommended and double the recommended doses of chlorantraniliprole. PMID- 26670041 TI - Measurement techniques for assessing the olfactory impact of municipal sewage treatment plants. AB - The study presents information about the measurement techniques used for the assessment of air quality in terms of the olfactory intensity resulting from the operation of municipal sewage treatment plants. Advantages and disadvantages of the measurement techniques used are presented. Sources of malodourous substance emission from sewage treatment plants were described, and the malodourous substances emitted were characterised. Trends in development of analysis and monitoring of the malodourous substances in the air were also presented. PMID- 26670043 TI - CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair. AB - Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy-consuming process. However, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of the cell-cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is reduced significantly in cells harboring CDK1 phosphorylation-deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair are also compromised severely in cells harboring mitochondrially targeted, kinase-deficient CDK1. These results demonstrate a mechanism governing the communication between mitochondria and the nucleus by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress conditions. PMID- 26670044 TI - In Vivo Monosynaptic Excitatory Transmission between Layer 2 Cortical Pyramidal Neurons. AB - Little is known about the properties of monosynaptic connections between identified neurons in vivo. We made multiple (two to four) two-photon targeted whole-cell recordings from neighboring layer 2 mouse somatosensory barrel cortex pyramidal neurons in vivo to investigate excitatory monosynaptic transmission in the hyperpolarized downstate. We report that pyramidal neurons form a sparsely connected (6.7% connectivity) network with an overrepresentation of bidirectional connections. The majority of unitary excitatory postsynaptic potentials were small in amplitude (<0.5 mV), with a small minority >1 mV. The coefficient of variation (CV = 0.74) could largely be explained by the presence of synaptic failures (22%). Both the CV and failure rates were reduced with increasing amplitude. The mean paired-pulse ratio was 1.15 and positively correlated with the CV. Our approach will help bridge the gap between connectivity and function and allow investigations into the impact of brain state on monosynaptic transmission and integration. PMID- 26670045 TI - Specific Myosins Control Actin Organization, Cell Morphology, and Migration in Prostate Cancer Cells. AB - We investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10, and Myo18a were expressed at higher levels in cells with high metastatic potential. Moreover, Myo1b and Myo10 were expressed at higher levels in metastatic tumors. Using an siRNA-based approach, we found that knockdown of each myosin resulted in distinct phenotypes. Myo10 knockdown ablated filopodia and decreased 2D migration speed. Myo18a knockdown increased circumferential non-muscle myosin 2A-associated actin filament arrays in the lamella and reduced directional persistence of 2D migration. Myo9b knockdown increased stress fiber formation, decreased 2D migration speed, and increased directional persistence. Conversely, Myo1b knockdown increased numbers of stress fibers but did not affect 2D migration. In all cases, the cell spread area was increased and 3D migration potential was decreased. Therefore, myosins not only act as molecular motors but also directly influence actin organization and cell morphology, which can contribute to the metastatic phenotype. PMID- 26670046 TI - LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes. AB - Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1) ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC), at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC's M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors. PMID- 26670047 TI - Elevated CaMKIIalpha and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model. AB - Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIalpha mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIalpha protein. Genetic or pharmacological inhibition of CaMKIIalpha or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIalpha, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder. PMID- 26670048 TI - Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization. AB - During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs) exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2) expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT)-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-beta-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization. PMID- 26670049 TI - A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors. AB - Immunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcgamma receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcgamma-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo. PMID- 26670050 TI - Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1. AB - In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these "decay-promoting" introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. PMID- 26670052 TI - High Prevalence of Nausea among School Children in Latin America. AB - OBJECTIVES: To evaluate the prevalence of nausea and its association with functional gastrointestinal disorders (FGIDs) in a large-scale, population-based study of Latin American school children. STUDY DESIGN: This cross-sectional study collected data from children in 3 Latin American countries. A Spanish version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS III) was administered to school children in Central and South America. Subjects were classified into FGIDs based on Rome criteria (QPGS-III). Students from 4 public and 4 private schools in the countries of El Salvador, Panama, and Ecuador participated in this epidemiologic study. RESULTS: A total of 1137 school children with mean age 11.5 (SD 1.9, range 8-15) years completed the QPGS-III (El Salvador n = 399; Panama n = 321; Ecuador n = 417). Nausea was present in 15.9% of all school children. Two hundred sixty-eight (24%) children met criteria for at least 1 FGID. Nausea was significantly more common in children with FGIDs compared with those without: El Salvador 38% vs 15% (P < .001); Panama 22% vs 7% (P < .001); Ecuador 25% vs 13% (P = .004). Among children with FGIDs, those with functional constipation had a high prevalence of nausea. Nausea was significantly more common in girls and children attending private schools. CONCLUSIONS: Nausea is commonly present in Latin American school children. FGIDs are frequently associated with nausea. PMID- 26670051 TI - Neocortical 40 Hz oscillations during carbachol-induced rapid eye movement sleep and cataplexy. AB - Higher cognitive functions require the integration and coordination of large populations of neurons in cortical and subcortical regions. Oscillations in the gamma band (30-45 Hz) of the electroencephalogram (EEG) have been involved in these cognitive functions. In previous studies, we analysed the extent of functional connectivity between cortical areas employing the 'mean squared coherence' analysis of the EEG gamma band. We demonstrated that gamma coherence is maximal during alert wakefulness and is almost absent during rapid eye movement (REM) sleep. The nucleus pontis oralis (NPO) is critical for REM sleep generation. The NPO is considered to exert executive control over the initiation and maintenance of REM sleep. In the cat, depending on the previous state of the animal, a single microinjection of carbachol (a cholinergic agonist) into the NPO can produce either REM sleep [REM sleep induced by carbachol (REMc)] or a waking state with muscle atonia, i.e. cataplexy [cataplexy induced by carbachol (CA)]. In the present study, in cats that were implanted with electrodes in different cortical areas to record polysomnographic activity, we compared the degree of gamma (30-45 Hz) coherence during REMc, CA and naturally-occurring behavioural states. Gamma coherence was maximal during CA and alert wakefulness. In contrast, gamma coherence was almost absent during REMc as in naturally-occurring REM sleep. We conclude that, in spite of the presence of somatic muscle paralysis, there are remarkable differences in cortical activity between REMc and CA, which confirm that EEG gamma (~40 Hz) coherence is a trait that differentiates wakefulness from REM sleep. PMID- 26670053 TI - Left Ventricular Mass Indexing in Infants, Children, and Adolescents: A Simplified Approach for the Identification of Left Ventricular Hypertrophy in Clinical Practice. AB - OBJECTIVE: To determine a simplified method to identify presence of left ventricular hypertrophy (LVH) in pediatric populations because the relationship between heart growth and body growth in children has made indexing difficult for younger ages. STUDY DESIGN: Healthy children (n = 400; 52% boys, 0-18 years of age) from 2 different European hospitals were studied to derive a simplified formula. Left ventricular mass (LVM) was calculated according to the Devereux formula. The derived approach to index LVM was tested on a validation cohort of 130 healthy children from a different hospital center. RESULTS: There was a strong nonlinear correlation between height and LVM. LVM was best related to height to a power of 2.16 with a correction factor of 0.09. Analysis of residuals for LVM/[(height(2.16)) + 0.09] showed an homoscedastic distribution in both sexes throughout the entire height range. A partition value of 45 g/m(2.16) was defined as the upper normal limit for LVM index. As opposed to formula suggested by current guidelines (ie, LVM/height(2.7)) when applying the proposed approach in the validation cohort of 130 healthy participants, no false positives for LVH were found (0% vs 8%; P < .01). CONCLUSIONS: Our data support the possibility to have a single partition (ie, 45 g/m(2.16)) value across the whole pediatric age range to identify LVH, without the time-consuming need of computing specific percentiles for height and sex. PMID- 26670054 TI - Design and synthesis of novel pegylated iron chelators with decreased metabolic rate. AB - BACKGROUND: Deferiprone has proved to be a successful iron selective chelator in a range of pathologies. However, its use is limited by rapid Phase II metabolism, necessitating the administration of large doses. In an attempt to modify metabolic rate of this class of compounds, a range of pegylated 3-hydroxypyridin 4-ones has been synthesized. EXPERIMENTAL: The synthetic route in which the polyethylene glycol counterparts are introduced to a protected pyran ring involves either a Williamson etherification reaction or direct addition leading to polyethylene glycol-containing precursors. RESULTS & DISCUSSION: The introduction of the pegylated substituent was found to lead to a relatively low rate of metabolism for some of the derivatives (6a, 6b, 8a and 8b), offering a possible improvement over deferiprone. PMID- 26670055 TI - Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids. AB - Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid-indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor-directed incorporation of cyanidin into a new 3' hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins. PMID- 26670056 TI - Fully Magnetically Levitated Left Ventricular Assist System for Treating Advanced HF: A Multicenter Study. AB - BACKGROUND: The HeartMate 3 left ventricular assist system (LVAS) is intended to provide long-term support to patients with advanced heart failure. The centrifugal flow pump is designed for enhanced hemocompatibility by incorporating a magnetically levitated rotor with wide blood-flow paths and an artificial pulse. OBJECTIVES: The aim of this single-arm, prospective, multicenter study was to evaluate the performance and safety of this LVAS. METHODS: The primary endpoint was 6-month survival compared with INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)-derived performance goal. Patients were adults with ejection fraction <= 25%, cardiac index <= 2.2 l/min/m(2) without inotropes or were inotrope-dependent on optimal medical management, or listed for transplant. RESULTS: Fifty patients were enrolled at 10 centers. The indications for LVAS support were bridge to transplantation (54%) or destination therapy (46%). At 6 months, 88% of patients continued on support, 4% received transplants, and 8% died. Thirty-day mortality was 2% and 6-month survival 92%, which exceeded the 88% performance goal. Support with the fully magnetically levitated LVAS significantly reduced mortality risk by 66% compared with the Seattle Heart Failure Model-predicted survival of 78% (p = 0.0093). Key adverse events included reoperation for bleeding (14%), driveline infection (10%), gastrointestinal bleeding (8%), and debilitating stroke (modified Rankin Score > 3) (8%). There were no pump exchanges, pump malfunctions, pump thrombosis, or hemolysis events. New York Heart Association classification, 6-min walk test, and quality-of-life scores showed progressive and sustained improvement. CONCLUSIONS: The results show that the fully magnetically levitated centrifugal-flow chronic LVAS is safe, with high 30-day and 6-month survival rates, a favorable adverse event profile, and improved quality of life and functional status. (HeartMate 3TM CE Mark Clinical Investigation Plan [HM3 CE Mark]; NCT02170363). PMID- 26670057 TI - Evolution in Mechanical Circulatory Support: Are We at the Precipice of a Disruptive Innovation? PMID- 26670058 TI - Outcome and Impact of Aortic Valve Replacement in Patients With Preserved LVEF and Low-Gradient Aortic Stenosis. AB - BACKGROUND: Low mean transvalvular gradient (<40 mm Hg) and small aortic valve area (<1.0 cm(2)) in patients with aortic stenosis (AS) and preserved left ventricular ejection fraction raises uncertainty about the actual severity of the stenosis and survival benefit of aortic valve replacement (AVR). OBJECTIVES: This study analyzed studies of mortality and survival impact of AVR in patients with low-gradient (LG) AS and preserved left ventricular ejection fraction, including paradoxical low-flow (i.e., stroke volume index <35 ml/m(2)), low-gradient (LF LG) and normal-flow, low-gradient (NF-LG), and those with high-gradient (>= 40 mm Hg) AS or moderate AS. METHODS: Studies published between 2005 and 2015 were analyzed. Primary outcome was the survival benefit associated with AVR. Secondary outcome was overall mortality regardless of treatment. RESULTS: Eighteen studies were included in the analysis. Patients with LF-LG AS have increased mortality compared with patients with moderate AS (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.31 to 2.17), NF-LG (HR: 1.80; 95% CI: 1.29 to 2.51), and high gradient (HR: 1.67; 95% CI: 1.16 to 2.39) AS. AVR was associated with reduced mortality in patients with LF-LG (HR: 0.44; 95% CI: 0.25 to 0.77). Similar benefit occurred with AVR in patients with NF-LG (HR: 0.48; 95% CI: 0.28 to 0.83). Compared with patients with high-gradient AS, those with LF-LG were less likely to be referred to AVR (odds ratio: 0.32; 95% CI: 0.21 to 0.49). CONCLUSIONS: Patients with paradoxical LF-LG AS and NF-LG AS have increased risk of mortality compared with other subtypes of AS with preserved left ventricular ejection fraction, and improved outcome with AVR. PMID- 26670059 TI - Low-Gradient Severe Aortic Stenosis With Preserved Ventricular Function: Trust But Verify. PMID- 26670060 TI - Utility of the Wearable Cardioverter-Defibrillator in Patients With Newly Diagnosed Cardiomyopathy: A Decade-Long Single-Center Experience. AB - BACKGROUND: The wearable cardioverter-defibrillator (WCD) has emerged as a means of protecting patients with newly diagnosed nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM) against sudden cardiac death while awaiting re evaluation of cardiac function. OBJECTIVES: This study sought to characterize the risk of appropriate WCD therapy in newly diagnosed NICM and ICM patients according to cardiomyopathy etiology in an independent study. METHODS: Medical records of all patients prescribed a WCD between June 2004 and May 2015 at our institution (n = 639) were analyzed, focusing on 254 patients with newly diagnosed NICM and 271 patients with newly diagnosed ICM. Patients with a prior implantable cardioverter-defibrillator or sustained ventricular arrhythmias were excluded (n = 114). The primary endpoint was appropriate WCD therapy. RESULTS: Median WCD wear time was 61 days (interquartile range [IQR]: 25 to 102 days) per patient and 22 h/day (IQR: 17 to 23 h/day). During 56.7 patient-years, 0 NICM patients received an appropriate WCD shock, whereas 3 (1.2%) received an inappropriate shock. During 46.7 patient-years, 6 (2.2%) ICM patients received an appropriate shock; 5 survived the episode, and 4 survived to hospital discharge. All 6 patients with an appropriate shock were male with QRS duration >120 ms. Two (0.7%) ICM patients received an inappropriate shock. CONCLUSIONS: In this independent, retrospective study, the risk of appropriate WCD therapies in patients with newly diagnosed NICM was minimal. Routine use of the WCD in this population should be prospectively evaluated. The risk of appropriate therapies in newly diagnosed ICM was comparable to that observed in prior observational studies. PMID- 26670061 TI - The Wearable Cardioverter-Defibrillator in Newly Diagnosed Cardiomyopathy: Treatment on the Basis of Perceived Risk. PMID- 26670062 TI - Comparative Effectiveness of CRT-D Versus Defibrillator Alone in HF Patients With Moderate-to-Severe Chronic Kidney Disease. AB - BACKGROUND: Patients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT). OBJECTIVES: This study sought to assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD. METHODS: We conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models. RESULTS: After risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages. CONCLUSIONS: In a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates. PMID- 26670063 TI - CRT for Heart Failure and ESRD: More Trials or More Thought Needed? PMID- 26670064 TI - Idiopathic Ventricular Arrhythmias Originating From the Pulmonary Sinus Cusp: Prevalence, Electrocardiographic/Electrophysiological Characteristics, and Catheter Ablation. AB - BACKGROUND: Idiopathic ventricular arrhythmias (VAs) originating from the pulmonary sinus cusp (PSC) have not been sufficiently clarified. OBJECTIVES: The goal of this study was to investigate the prevalence, electrocardiographic characteristics, mapping, and ablation of idiopathic VAs arising from the PSC. METHODS: Data were analyzed from 218 patients undergoing successful endocardial ablation of idiopathic VAs with a left bundle branch block morphology and inferior axis deviation. RESULTS: Twenty-four patients had VAs originating from the PSC. In the first 7 patients, initial ablation performed in the right ventricular outflow tract failed to abolish the clinical VAs but produced a small change in the QRS morphology in 3 patients. In all 24 patients, the earliest activation was eventually identified in the PSC, at which a sharp potential was observed preceding the QRS complex onset by 28.2 +/- 2.9 ms. The successful ablation site was in the right cusp (RC) in 10 patients (42%), the left cusp (LC) in 8 (33%), and the anterior cusp (AC) in 6 (25%). Electrocardiographic analysis showed that RC-VAs had significantly larger R-wave amplitude in lead I and a smaller aVL/aVR ratio of Q-wave amplitude compared with AC-VAs and LC-VAs, respectively. The R-wave amplitude in inferior leads was smaller in VAs localized in the RC than in the LC but did not differ between VAs from the AC and LC. CONCLUSIONS: VAs arising from the PSC are not uncommon, and RC-VAs have unique electrocardiographic characteristics. These VAs can be successfully ablated within the PSC. PMID- 26670065 TI - Pulmonic Cusp Ablation: Novel Mechanism or a New Approach to an Old Problem? PMID- 26670066 TI - Statistical Controversies in Reporting of Clinical Trials: Part 2 of a 4-Part Series on Statistics for Clinical Trials. AB - This paper tackles several statistical controversies that are commonly faced when reporting a major clinical trial. Topics covered include: multiplicity of data, interpreting secondary endpoints and composite endpoints, the value of covariate adjustment, the traumas of subgroup analysis, assessing individual benefits and risks, alternatives to analysis by intention to treat, interpreting surprise findings (good and bad), and the overall quality of clinical trial reports. All is put in the context of topical cardiology trial examples and is geared to help trialists steer a wise course in their statistical reporting, thereby giving readers a balanced account of trial findings. PMID- 26670067 TI - Hemodynamics of Mechanical Circulatory Support. AB - An increasing number of devices can provide mechanical circulatory support (MCS) to patients with acute hemodynamic compromise and chronic end-stage heart failure. These devices work by different pumping mechanisms, have various flow capacities, are inserted by different techniques, and have different sites from which blood is withdrawn and returned to the body. These factors result in different primary hemodynamic effects and secondary responses of the body. However, these are not generally taken into account when choosing a device for a particular patient or while managing a patient undergoing MCS. In this review, we discuss fundamental principles of cardiac, vascular, and pump mechanics and illustrate how they provide a broad foundation for understanding the complex interactions between the heart, vasculature, and device, and how they may help guide future research to improve patient outcomes. PMID- 26670068 TI - A Micro View of MACRA: How the ACC and NCDR Will Help Members Navigate Radical Changes Ahead. PMID- 26670069 TI - Hospital Variation in Outcomes for Transcatheter Aortic Valve Replacement Among Medicare Beneficiaries, 2011 to 2013. PMID- 26670070 TI - Effect of Vitamin D Supplementation on Aortic Stiffness and Arterial Hemodynamics in People With Osteoarthritis and Vitamin D Deficiency. PMID- 26670071 TI - Anticoagulant-Related Nephropathy. PMID- 26670072 TI - Reply: Anticoagulant-Related Nephropathy. PMID- 26670073 TI - Hypochloremia in Acute Decompensated Heart Failure. PMID- 26670074 TI - Reply: Hypochloremia in Acute Decompensated Heart Failure. PMID- 26670075 TI - Reply: Living Up to the PROMISE: Is There an Ultimate Winner? PMID- 26670076 TI - Impact of unilateral versus bilateral laparoscopic ovarian drilling on ovarian reserve and pregnancy rate: a randomized clinical trial. AB - OBJECTIVE: To assess the impact of unilateral dose adjusted ovarian drilling (ULOD) compared to bilateral ovarian drilling (BLOD) on ovarian reserve and pregnancy rate. METHODS: This randomized clinical study included 105 patients with polycystic ovary syndrome. Patients were assigned to two groups; group 1 (n = 52) underwent dose adjusted ULOD using 60 Joules/cm(3) applied to the larger ovary, while group 2 (n = 53) underwent BLOD with fixed doses of 1200 J. Ovulation rate, anti-Mullerian hormone (AMH), antral follicle count (AFC), and pregnancy rates were assessed at 3 and 6 months of follow-up. RESULTS: Ovulation and pregnancy rates at 3 months periods were comparable (p > 0.05), but was significantly higher in BLOD at 6 months period (p < 0.05). There was a highly significant difference between the two groups regarding the AMH level at 3- and 6 month follow-up periods (p < 0.001) with lower levels in the BLOD group. The AFC was comparable in the two groups after 3 months (p > 0.05) but became higher in the ULOD at 6-month follow-up period (p < 0.001). CONCLUSION: Dose-adjusted ULOD applied to the larger ovary has comparable ovulation and pregnancy rates to fixed dose BLOD at 3-month follow-up periods with decrease in its effectiveness after 6 months. PMID- 26670077 TI - Potential of alpha-fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma. AB - AIM: Recurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by alpha-fetoprotein (AFP). METHODS: We enrolled 357 consecutive patients who underwent complete ablation by RFA for primary HCC (<=3 cm, <=3 tumors) and analyzed the correlation between 17 critical parameters, including AFP and HCC recurrence. RESULTS: Recurrence was observed in 236 patients during a mean observation period of 54.3 months. Multivariate analysis revealed that multiple tumors (risk ratio [RR] = 1.70, 95% confidence interval [CI] = 1.27-2.26, P < 0.001), high AFP (>10 ng/mL, RR = 1.45, 95% CI = 1.09-1.94, P < 0.001) and high des-gamma-carboxyprothrombin (>40 mAU/mL, RR = 1.52, 95% CI = 1.13-2.02, P < 0.005) were significantly correlated with recurrence. AFP was selected as a significant factor even when the cut-off level was set lower (<=5 ng/mL). The risk of recurrence increased linearly according to the increase of the lowest AFP level after RFA and the adjusted ratios relative to AFP less than 5 ng/mL were 1.56, 2.14, 2.57 and 3.13 in AFP 5-10 ng/mL, 10-20 ng/mL, 20-50 ng/mL and over 50 ng/mL, respectively. In addition, the recurrence rate was predicted by the AFP level after RFA, regardless of the level before the treatment. CONCLUSION: AFP less than 5 ng/mL after curative RFA was an important predictor of a better prognosis and was considered to indicate the low carcinogenic potential of the non-cancerous liver. PMID- 26670078 TI - Impact of food intake on in vivo VOC concentrations in exhaled breath assessed in a caprine animal model. AB - Physiological processes within the body may change emitted volatile organic compound (VOC) composition, and may therefore cause confounding biological background variability in breath gas analyses. To evaluate the effect of food intake on VOC concentration patterns in exhaled breath, this study assessed the variability of VOC concentrations due to food intake in a standardized caprine animal model. VOCs in (i) alveolar breath gas samples of nine clinically healthy goats and (ii) room air samples were collected and pre-concentrated before morning feeding and repeatedly after (+60 min, +150 min, +240 min) using needle trap microextraction (NTME). Analysis of VOCs was performed by gas chromatography and mass spectrometry (GC-MS). Only VOCs with significantly higher concentrations in breath gas samples compared to room air samples were taken into consideration. Six VOCs that belonged to the chemical classes of hydrocarbons and alcohols were identified presenting significantly different concentrations before and after feeding. Selected hydrocarbons showed a concentration pattern that was characterized by an initial increase 60 min after food intake, and a subsequent gradual decrease. Results emphasize consideration of physiological effects on exhaled VOC concentrations due to food intake with respect to standardized protocols of sample collection and critical evaluation of results. PMID- 26670080 TI - Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps. AB - Neocarazostatin A (NZS) is a bacterial alkaloid with promising bioactivities against free radicals, featuring a tricyclic carbazole nucleus with a prenyl moiety at C-6 of the carbazole ring. Here, we report the discovery and characterization of the biosynthetic pathway of NZS through genome mining and gene inactivation. The in vitro assays characterized two enzymes: NzsA is a P450 hydroxylase and NzsG is a new phytoene-synthase-like prenyltransferase (PTase). This is the first reported native PTase that specifically acts on the carbazole nucleus. Finally, our in vitro reconstituted experiment demonstrated a coupled reaction catalyzed by NzsG and NzsA tailoring the NZS biosynthesis. PMID- 26670079 TI - Reciprocal Regulation of ERalpha and ERbeta Stability and Activity by Diptoindonesin G. AB - ERbeta is regarded as a "tumor suppressor" in breast cancer due to its anti proliferative effects. However, unlike ERalpha, ERbeta has not been developed as a therapeutic target in breast cancer due to loss of ERbeta in aggressive cancers. In a small-molecule library screen for ERbeta stabilizers, we identified Diptoindonesin G (Dip G), which significantly increases ERbeta protein stability while decreasing ERalpha protein levels. Dip G enhances the transcription and anti-proliferative activities of ERbeta, while attenuating the transcription and proliferative effects of ERalpha. Further investigation revealed that instead of targeting ER, Dip G targets the CHIP E3 ubiquitin ligase shared by ERalpha and ERbeta. Thus, Dip G is a dual-functional moiety that reciprocally controls ERalpha and ERbeta protein stability and activities via an indirect mechanism. The ERbeta stabilization effects of Dip G may enable the development of ERbeta targeted therapies for human breast cancers. PMID- 26670081 TI - Transcriptional Profiling of a Selective CREB Binding Protein Bromodomain Inhibitor Highlights Therapeutic Opportunities. AB - Bromodomains are involved in transcriptional regulation through the recognition of acetyl lysine modifications on diverse proteins. Selective pharmacological modulators of bromodomains are lacking, although the largely hydrophobic nature of the pocket makes these modules attractive targets for small-molecule inhibitors. This work describes the structure-based design of a highly selective inhibitor of the CREB binding protein (CBP) bromodomain and its use in cell-based transcriptional profiling experiments. The inhibitor downregulated a number of inflammatory genes in macrophages that were not affected by a selective BET bromodomain inhibitor. In addition, the CBP bromodomain inhibitor modulated the mRNA level of the regulator of G-protein signaling 4 (RGS4) gene in neurons, suggesting a potential therapeutic opportunity for CBP inhibitors in the treatment of neurological disorders. PMID- 26670083 TI - Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis. AB - BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with poor clinical outcome in ischemic and hemorrhagic stroke. Admission hyperglycemia has not been investigated in patients with cerebral venous thrombosis. METHODS: Consecutive adult patients with cerebral venous thrombosis were included at the Academic Medical Center, The Netherlands (2000-2014) and the Helsinki University Central Hospital, Finland (1998-2014). We excluded patients with known diabetes mellitus and patients without known admission blood glucose. We defined admission hyperglycemia as blood glucose >=7.8 mmol/L (141 mg/dL) and severe hyperglycemia as blood glucose >=11.1 mmol/L (200 mg/dL). We used logistic regression analysis to determine if admission hyperglycemia was associated with modified Rankin Scale (mRS) score of 3 to 6 or mortality at last follow-up. We adjusted for: age, sex, coma, malignancy, infection, intracerebral hemorrhage, deep cerebral venous thrombosis, and location of recruitment. RESULTS: Of 380 patients with cerebral venous thrombosis, 308 were eligible. Of these, 66 (21.4%) had admission hyperglycemia with 8 (2.6%) having severe admission hyperglycemia. Coma (31.3% versus 5.0%, P<0.001) and intracerebral hemorrhage (53.0% versus 32.6%, P=0.002) at presentation were more common among patients with admission hyperglycemia than normoglycemic patients. Patients with admission hyperglycemia had a higher risk of mRS score of 3 to 6 (adjusted odds ratio, 3.10; 95% confidence interval, 1.35 7.12) and mortality (adjusted odds ratio, 4.13; 95% confidence interval, 1.41 12.09). Severe hyperglycemia was even more strongly associated with mRS score of 3 to 6 (adjusted odds ratio, 11.59; 95% confidence interval, 1.74-77.30) and mortality (adjusted odds ratio, 33.36; 95% confidence interval, 3.87-287.28) compared with normoglycemic patients. CONCLUSIONS: Admission hyperglycemia is a strong predictor of poor clinical outcome in patients with cerebral venous thrombosis. PMID- 26670082 TI - Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black-Blood Thrombus Imaging. AB - BACKGROUND AND PURPOSE: Early diagnosis of cerebral venous thrombosis (CVT) is currently a major clinical challenge. We proposed a novel magnetic resonance black-blood thrombus imaging technique (MRBTI) for detection and quantification of CVT. METHODS: MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into 2 groups based on the duration of clinical onset: <=7 days (group 1) and between 7 and 30 days (group 2). Signal/noise ratio was calculated for the detected thrombus, and contrast/noise ratio was measured between thrombus and lumen and also between thrombus and brain tissue. The feasibility of using MRBTI for thrombus volume measurement was explored, and total thrombus volume was calculated for each patient. RESULTS: In 23 patients with proven CVT, MRBTI correctly identified 113 of 116 segments with a sensitivity of 97.4%. Thrombus signal/noise ratio was 153+/-57 and 261+/-95 for group 1 (n=10) and group 2 (n=13), respectively (P<0.01). Thrombus to lumen contrast/noise ratio was 149+/ 57 and 256+/-94 for group 1 and group 2, respectively. Thrombus to brain tissue contrast/noise ratio was 41+/-36 and 120+/-63 (P<0.01), respectively. Quantification of thrombus volume was successfully conducted in all patients with CVT, and mean volume of thrombus was 10.5+/-6.9 mL. CONCLUSIONS: The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first-line diagnostic imaging tool. PMID- 26670085 TI - Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan. AB - BACKGROUND AND PURPOSE: Argatroban, a selective thrombin inhibitor, is recommended for the use in patients with atherothrombotic stroke by the Japanese Guidelines for the Management of Patients with Acute Ischemic Stroke. We performed a nationwide Japanese study to investigate whether argatroban improved early stroke outcomes in patients with acute atherothrombotic stroke. METHODS: This retrospective observational study, using the Diagnosis Procedure Combination database in Japan, included patients who were hospitalized from July 1, 2010, to March 31, 2012, with a diagnosis of atherothrombotic stroke within 1 day of stroke onset. Patients were divided into 2 groups: those receiving argatroban on admission (argatroban group), and those who did not receive argatroban during hospitalization (control group). To balance the baseline characteristics and concomitant treatments during hospitalization between the 2 groups, one-to-one propensity-score matching analyses were performed. The main outcomes were the modified Rankin Scale score at discharge and the occurrence of hemorrhagic complications during hospitalization. An ordinal logistic regression analysis evaluated the association between argatroban use and modified Rankin Scale at discharge. RESULTS: After propensity-score matching, 2289 pairs of patients were analyzed. There were no significant differences in modified Rankin Scale at discharge between the argatroban and the control groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.88-1.16). The occurrence of hemorrhagic complications did not differ significantly between the argatroban and the control groups (3.5% versus 3.8%; P=0.58). CONCLUSIONS: The present study suggested that argatroban was safe, but had no added benefit in early outcomes after acute atherothrombotic stroke. PMID- 26670086 TI - Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies. AB - BACKGROUND AND PURPOSE: The association between hemorrhagic stroke and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established. We conducted a systematic review and meta-analysis of observation studies to further characterize this possible association. METHODS: Case-control and cohort studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of hemorrhagic stroke among NSAIDs users versus nonusers were systematically searched. Point estimates from each study were extracted. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and individual NSAIDs were calculated using random-effect, generic inverse variance method. RESULTS: Ten studies were identified and included in our data analysis. As a single group, NSAIDs use was associated with a small but insignificant risk of hemorrhagic stroke with the pooled RR of 1.09 (95% CI, 0.98-1.22). Individual NSAIDs analysis revealed a significantly increased risk among diclofenac and meloxicam users (RR 1.27; 95% CI, 1.02-1.59 and RR 1.27; 95% CI, 1.08-1.50, respectively). The risk estimate for rofecoxib users was higher, but statistically nonsignificant (RR 1.35; 95% CI, 0.88-2.06). CONCLUSIONS: Overall, the use of NSAIDs is not associated with an increased risk of hemorrhagic stroke, although this risk was modestly significantly elevated in diclofenac and meloxicam users. PMID- 26670084 TI - Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion. AB - BACKGROUND AND PURPOSE: Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. RESULTS: Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. CONCLUSIONS: White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. PMID- 26670087 TI - Pre-frontal-insular-cerebellar modifications correlate with disgust feeling blunting after subthalamic stimulation: A positron emission tomography study in Parkinson's disease. AB - Subthalamic nucleus (STN) deep brain stimulation (DBS) has recently advanced our understanding of the major role played by this basal ganglion in human emotion. Research indicates that STN DBS can induce modifications in all components of emotion, and neuroimaging studies have shown that the metabolic modifications correlated with these emotional disturbances following surgery are both task- and sensory input-dependent. Nevertheless, to date, these modifications have not been confirmed for all emotional components, notably subjective emotional experience, or feelings. To identify the neural network underlying the modification of feelings following STN DBS, we assessed 16 patients with Parkinson's disease before and after surgery, using both subjective assessments of emotional experience and 18 [F]fluorodeoxyglucose positron emission tomography (18 FDG PET). The patients viewed six film excerpts intended to elicit happy, angry, fearful, sad, disgusted, and neutral feelings, and they self-rated the intensity of these feelings. After DBS, there was a significant reduction in the intensity of the disgust feeling. Correlations were observed between decreased disgust experience and cerebral glucose metabolism (FDG uptake) in the bilateral pre frontal cortices (orbitofrontal, dorsolateral, and inferior frontal gyri), bilateral insula, and right cerebellum. We suggest that the STN contributes to the synchronization process underlying the emergence of feelings. PMID- 26670089 TI - Cancer drugs in 16 European countries, Australia, and New Zealand: a cross country price comparison study. AB - BACKGROUND: Cancer drugs challenge health-care systems because of their high prices. No cross-country price comparison of cancer drugs for a large number of countries has been published. We aimed to survey the prices of cancer drugs in high-income countries (Europe, Australia, and New Zealand). METHODS: Based on comparability in terms of the economic situation and of the pharmaceutical system, we surveyed official list prices per unit at ex-factory price level of 31 originator cancer drugs in 16 European countries, Australia, and New Zealand as of June, 2013. Drug price data for the European countries were provided by the Pharma Price Information (PPI) service; Australian and New Zealand drug price data were retrieved from the respective pharmaceutical schedules. FINDINGS: In Austria, Denmark, Finland, Germany, Italy, Norway, Sweden, and the UK, price information was available for all or all but one drug surveyed whereas the availability of price data was restricted for some drugs in other countries, especially in New Zealand and Portugal. The difference of a drug price between the highest priced country and the lowest priced country varied between 28% and 388%. A few drugs had lower outliers, especially Greek and UK prices, and upper outliers (particularly prices in Switzerland, Germany, and Sweden). Overall, Greek prices ranked at a low level, whereas Sweden, Switzerland, and Germany showed price data in similarly high ranges. INTERPRETATION: Our results showed variations in ex-factory prices of originator cancer drugs in the 18 surveyed countries. However, the surveyed prices do not include discounts negotiated by funding organisations because these discounts are confidential. Because pricing authorities can also only use these official undiscounted prices when they set prices through the common policy of external price referencing, they risk overpaying. Our findings provide an evidence base for policy makers to decide whether further policy measures related to drug prices are needed. FUNDING: None. PMID- 26670090 TI - Cervical cancer diagnosis and the US Affordable Care Act. PMID- 26670088 TI - An evaluation of new and established methods to determine T-DNA copy number and homozygosity in transgenic plants. AB - Stable transformation of plants is a powerful tool for hypothesis testing. A rapid and reliable evaluation method of the transgenic allele for copy number and homozygosity is vital in analysing these transformations. Here the suitability of Southern blot analysis, thermal asymmetric interlaced (TAIL-)PCR, quantitative (q)PCR and digital droplet (dd)PCR to estimate T-DNA copy number, locus complexity and homozygosity were compared in transgenic tobacco. Southern blot analysis and ddPCR on three generations of transgenic offspring with contrasting zygosity and copy number were entirely consistent, whereas TAIL-PCR often underestimated copy number. qPCR deviated considerably from the Southern blot results and had lower precision and higher variability than ddPCR. Comparison of segregation analyses and ddPCR of T1 progeny from 26 T0 plants showed that at least 19% of the lines carried multiple T-DNA insertions per locus, which can lead to unstable transgene expression. Segregation analyses failed to detect these multiple copies, presumably because of their close linkage. This shows the importance of routine T-DNA copy number estimation. Based on our results, ddPCR is the most suitable method, because it is as reliable as Southern blot analysis yet much faster. A protocol for this application of ddPCR to large plant genomes is provided. PMID- 26670091 TI - Herbal medicines safety concerns in patients with cancer. PMID- 26670092 TI - Internal mammary node irradiation and breast cancer survival. PMID- 26670093 TI - Actual costs of cancer drugs in 15 European countries. PMID- 26670094 TI - Intraventricular apolipoprotein ApoJ infusion acts protectively in Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in youth, but to date, effective therapies are still lacking. Previous studies revealed a marked response of apolipoprotein J (ApoJ) expression to the brain injury. The aim of this study was to determine the potential roles of ApoJ in functional recovery following TBI. After controlled cortex impact (CCI), a TBI model, in adult wild-type mice, ApoJ expression was up-regulated since 6 h post injury and sustained for 5 days. Animals infused with recombinant human ApoJ intraventricularly at 30 min prior to CCI showed significantly reduced oxidative stress (3-nitrotyrosine, 4-hydroxynonenal) and complement activation (C5b-9). In addition, ApoJ treatment was shown to suppress the inflammatory response (glial activation, cytokine expression), blood-brain barrier disruption (Evans blue extravasation), and cerebral edema (water content) induced by CCI. Concomitantly, improved neuronal maintenance and neurological behavioral performance were observed in ApoJ-treated mice compared with the vehicle group. These findings support a neuroprotective role of ApoJ via multifunctional pathways, providing a novel and encouraging treatment strategy for TBI. Apolipoprotein J (ApoJ) was up regulated after controlled cortical impact (CCI). Mice infused with human recombinant ApoJ prior to CCI showed reduced expression of complement and oxidative marker proteins as well as reduced inflammatory response and attenuated blood-brain barrier (BBB) disruption and cerebral edema. Neuronal maintenance and behavioral performance were improved by ApoJ infusion. These findings demonstrated the protective function of ApoJ for traumatic brain injury (TBI) therapy. PMID- 26670095 TI - Computed Tomography in Congenital Heart Disease: Clinical Applications and Technical Considerations. AB - Computed tomography (CT) is increasingly applied as an aid to clinical decision making in congenital heart disease (CHD) with regard to surgery, interventional catheterizations, and follow-up. It is particularly useful for the assessment of vascular and airway abnormalities. Updated knowledge of CT imaging techniques is mandatory not only for the optimization of image acquisition protocols, but also for the postprocessing reconstruction and interpretation of CT findings. The purpose of this article was to review the clinical indications, techniques, and dose reduction methods for CT imaging in children and adults with CHD. Relevant discussion and illustrations of common forms of CHD evaluated by CT are presented. PMID- 26670096 TI - Reference Range of Platelet Delta Granules in the Pediatric Age Group: An Ultrastructural Study of Platelet Whole Mount Preparations from Healthy Volunteers. AB - This study sought to determine delta granule normal ranges for children and to validate methodology for the appropriate diagnosis of delta granule deficiency (storage pool disease) by using the whole-mount technique in electron microscopy. Specimens obtained from 40 healthy volunteers (2 months of age through 21 years old, 21 females and 19 males) were tested. Results showed dense granules/platelet (DG/Plt) ranged from 1.78 to 5.25. The 5th percentile was 1.96 DG/Plt with an overall mean +/- SEM 3.07 +/- 0.12 DG/Plt. In comparison, a previously published lower cutoff value, 3.68 DG/Plt, was significantly higher than the mean from our volunteers (P < 0.0001). We found no variability in dense granules/platelet based on race or sex and no significant variation by age subgroup. Pending wider studies, the value of 2 DG/Plt is a more appropriate lower limit of normal. In the absence of wider studies (in healthy volunteers and patients), laboratories should consider establishing their own reference ranges. PMID- 26670097 TI - Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease. AB - MicroRNAs (miRNAs) are small noncoding RNAs that serve as key regulators of gene expression. They have been shown to be involved in a wide range of biological processes including neurodegenerative diseases. Genetic variants in miRNAs or miRNA-binding sites on their target genes could affect miRNA function and contribute to disease risk. Here, we investigated the association of miRNA related genetic variants with Parkinson disease (PD) using data from the largest GWAS on PD. Of 243 miRNA variants, we identified rs897984:T>C in miR-4519 (P value = 1.3*10(-5) and OR = 0.93) and rs11651671:A>G in miR-548at-5p (P value = 1.1*10(-6) and OR = 1.09) to be associated with PD. We showed that the variant's mutant alleles change the secondary structure and decrease expression level of their related miRNAs. Subsequently, we highlighted target genes that might mediate the effects of miR-4519 and miR-548at-5p on PD. Among them, we experimentally showed that NSF is a direct target of miR-4519. Furthermore, among 48,844 miRNA-binding site variants, we found 32 variants (within 13 genes) that are associated with PD. Four of the host genes, CTSB, STX1B, IGSF9B, and HSD3B7, had not previously been reported to be associated with PD. We provide evidence supporting the potential impact of the identified miRNA-binding site variants on miRNA-mediated regulation of their host genes. PMID- 26670098 TI - Dermatomyositis: factors predicting relapse. AB - BACKGROUND: The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. OBJECTIVE: The aim of this study was to identify presentation features that predict DM relapses. METHODS: We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. RESULTS: We identified 34 patients, with a mean age of 46 +/- 17 years (range, 18 77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2 8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2-7.9)]. CONCLUSION: Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course. PMID- 26670099 TI - Morphological characteristics and genetic diversity of Burmese long-tailed Macaques (Macaca fascicularis aurea). AB - Macaca fascicularis aurea (Mfa) is the only macaque which has been recorded to use stone tools to access encased foods. They live in close contact with M. fascicularis fascicularis (Mff) in southwestern Thailand and the hybrids were reported [Fooden, 1995]. Although Mff and Mfa can be seen in the same habitat types, tool-use behavior has never been reported in Mff. Thus, comparing the morphological characteristics and genetics between Mfa and Mff should help elucidate not only the morphological differences and genetic divergence between these subspecies but also potentially the relationship between genetics and their tool use behavior. We surveyed Mfa and Mff in Myanmar and Thailand, ranging from 16 degrees 58' to 7 degrees 12' N. Fecal or blood samples were collected from eight, five, and four populations of Mfa, Mff, and Mff * Mfa morphological hybrids along with three individuals of captive Chinese M. mulatta (Mm), respectively, for mtDNA and Y-chromosome (TSPY and SRY genes) DNA sequence analyses. In addition, eight populations were captured and measured for 38 somatometric dimensions. Comparison of the somatic measurements revealed that Mfa had a statistically significantly shorter tail than Mff (P < 0.05). Based on the mtDNA sequences, Mfa was separated from the Mm/Mff clade. Within the Mfa clade, the mainland Myanmar population was separate from the Mergui Archipelago and Thailand Andaman seacoast populations. All the morphological hybrids had the Mff mtDNA haplotype. Based on the Y-chromosome sequences, the three major clades of Mm/Indochinese Mff, Sundaic Mff, and Mfa were constructed. The hybrid populations grouped either with the Mm/Indochinese Mff or with the Mfa. Regarding the genetic analysis, one subspecies hybrid population in Thailand (KRI) elicited tool use behavior, thus the potential role of genetics in tool use behavior is raised in addition to the environmental force, morphological suitability, and cognitive capability. Am. J. Primatol. 78:441-455, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26670101 TI - Prehypertension and Chronic Kidney Disease in Chinese Population: Four-Year Follow-Up Study. AB - Hypertension is a well established cause of chronic kidney disease (CKD). However, the effect of prehypertension on risk of CKD is controversial. The aim of this study is to determine whether prehypertension increases the risk of CKD events in the Chinese population. We enrolled 20,034 with prehypertension and 12,351 with ideal blood pressure in this prospective study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min 1.73 m2. The new occurrences of CKD events were collected during follow-up. Cumulative survival and freedom for the occurrence of new CKD events was analyzed using the Kaplan Meier approach. Multivariate Cox Regression was used to analyze the effect of prehypertension on CKD. The median follow-up time was 47 (interquartile range 44 51) months. 601 new onset CKD events occurred during the follow-up period. The cumulative incidence of new CKD events was higher in the prehypertensive population than that in the ideal blood pressure population (2.10% vs 1.46%, P = 0.0001). Multivariate Cox Regression showed that relative risks (RRs) for the new onset CKD events in the prehypertensive population were 1.69 (95% confidence intervals (CI): 1.41~2.04, P = 0.001) higher than those in the ideal blood pressure population. Similarly, the risks were 1.68 (95% CI: 1.33~2.13 P = 0.001) times higher in females and 2.14 (95% CI: 1.58~2.91 P = 0.001) times higher in males by adjustment for traditional CV risk factors. Our findings demonstrated prehypertension is an independent risk factor for the occurrence of new CKD events in the Chinese population. PMID- 26670102 TI - Comparing approaches to controlling medicare spending. PMID- 26670103 TI - Highly Durable and Active PtFe Nanocatalyst for Electrochemical Oxygen Reduction Reaction. AB - Demand on the practical synthetic approach to the high performance electrocatalyst is rapidly increasing for fuel cell commercialization. Here we present a synthesis of highly durable and active intermetallic ordered face centered tetragonal (fct)-PtFe nanoparticles (NPs) coated with a "dual purpose" N doped carbon shell. Ordered fct-PtFe NPs with the size of only a few nanometers are obtained by thermal annealing of polydopamine-coated PtFe NPs, and the N doped carbon shell that is in situ formed from dopamine coating could effectively prevent the coalescence of NPs. This carbon shell also protects the NPs from detachment and agglomeration as well as dissolution throughout the harsh fuel cell operating conditions. By controlling the thickness of the shell below 1 nm, we achieved excellent protection of the NPs as well as high catalytic activity, as the thin carbon shell is highly permeable for the reactant molecules. Our ordered fct-PtFe/C nanocatalyst coated with an N-doped carbon shell shows 11.4 times-higher mass activity and 10.5 times-higher specific activity than commercial Pt/C catalyst. Moreover, we accomplished the long-term stability in membrane electrode assembly (MEA) for 100 h without significant activity loss. From in situ XANES, EDS, and first-principles calculations, we confirmed that an ordered fct-PtFe structure is critical for the long-term stability of our nanocatalyst. This strategy utilizing an N-doped carbon shell for obtaining a small ordered-fct PtFe nanocatalyst as well as protecting the catalyst during fuel cell cycling is expected to open a new simple and effective route for the commercialization of fuel cells. PMID- 26670104 TI - The immune system and nutrition: Homing in on complex interactions. PMID- 26670100 TI - Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study. AB - BACKGROUND: Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. PATIENTS AND METHODS: A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. RESULTS: None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50-3.70], P = 2x10(-4)). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82-8.92], P = 8x10(-4)). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10(-5)). CONCLUSION: Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy. PMID- 26670105 TI - Penetrating duodenal trauma: A 19-year experience. AB - BACKGROUND: Multiple techniques are used for repair in duodenal injury ranging from simple suture repair for low-grade injuries to pancreaticoduodenectomy for complicated high-grade injuries. Drains, both intraluminal and extraluminal, are placed variably depending on associated injuries and confidence with the repair. It is our contention that a simplified approach to repair will limit complications and mortality. The major complication of duodenal leak (DL) was the outcome used to assess methods of repair in this study. METHODS: After early deaths from associated vascular injuries were excluded, patients with a penetrating duodenal injury admitted during a 19-year period ending in 2014 constituted the study population. RESULTS: A total of 125 patients with penetrating duodenal injuries were included. Overall, the leak rate was 8% with two duodenal-related mortalities. No differences were seen in patients who had a DL as compared with no leak with respect to demographics, injury severity, or admission variables. Patients with DL were more likely to have a major vascular injury (60% vs. 23%, p = 0.02) and a combined pancreatic injury (70% vs. 31%, p = 0.03). No differences were identified by repair technique, location, or grade of injury. DLs were more likely to have an extraluminal drain (90% vs. 45%, p = 0.008). CONCLUSION: Primary suture repair should be the initial approach considered for most injuries. Major vascular injuries and concomintant pancreatic injuries were associated with most leaks; therefore, adjuncts to repair including intraluminal drainage and pyloric exclusion should be considered on the initial operation. Extraluminal drains should be avoided unless required for associated injuries. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV. PMID- 26670106 TI - Re: Assessment of acute kidney injury following severe trauma. PMID- 26670107 TI - Assessment of acute kidney injury following severe trauma. PMID- 26670108 TI - Needle thoracostomy: Clinical effectiveness is improved using a longer angiocatheter. AB - BACKGROUND: Decompression of tension physiology may be lifesaving, but significant doubts remain regarding ideal needle thoracostomy (NT) catheter length in the treatment of tension physiology. We aimed to demonstrate increased clinical effectiveness of longer NT angiocatheter (8 cm) compared with current Advanced Trauma Life Support recommendations of 5-cm NT length. METHODS: This is a retrospective review of all adult trauma patients from 2003 to 2013 (age > 15 years) transported to a Level I trauma center. Patients underwent NT at the second intercostal space midclavicular line, either at the scene of injury, during transport (prehospital), or during initial hospital trauma resuscitation. Before March 2011, both prehospital and hospital trauma team NT equipment routinely had a 5-cm angiocatheter available. After March 2011, prehospital providers were provided an 8-cm angiocatheter. Effectiveness was defined as documented clinical improvement in respiratory, cardiovascular, or general clinical condition. RESULTS: There were 91 NTs performed on 70 patients (21 bilateral placements) either in the field (prehospital, n = 41) or as part of resuscitation in the hospital (hospital, n = 29). Effectiveness of NT was 48% until March 2011 (n = 24). NT effectiveness was significantly higher in the prehospital setting than in the hospital (68.3% success rate vs. 20.7%, p < 0.01). Patients who underwent NT using 8 cm compared with 5 cm were significantly more effective (83% vs. 41%, respectively, p = 0.01). No complications of NT were identified in either group. CONCLUSION: Eight-centimeter angiocatheters are more effective at chest decompression compared with currently recommended 5 cm at the second intercostal space midclavicular line. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26670110 TI - Airway management following repair of cervical tracheal injuries: A retrospective, multicenter study. AB - BACKGROUND: Optimal airway management following repair of cervical tracheal injuries is unknown. This study aimed to determine the optimal airway strategy following cervical tracheal injury repair. METHODS: Patients with cervical tracheal injuries admitted from January 2000 to January 2014 at seven US Level I trauma centers were identified. Patients were grouped depending on postoperative airway management: immediate or early extubation (<=24 hours, EXT), prolonged intubation (>24 hours, INT), and immediate tracheostomy (TRACH). Following univariate analysis, a multivariate model was then developed to evaluate for surgical site infection (SSI) and intensive care unit-free and ventilator-free days, comparing INT and TRACH with EXT as the reference. RESULTS: A total of 120 cervical tracheal injuries were treated at seven Level I trauma centers. Ten patients were excluded for incomplete data, and seven died within 24 hours of admission, leaving 103 patients included in the study. Patients were grouped based on airway management: 40 (39%) in the EXT, 30 (29%) in the INT, and 33 (32%) in the TRACH group. There were no differences in demographics or injury mechanism. The INT and TRACH groups were more severely injured than the EXT group (median Injury Severity Score [ISS]: INT, 25; TRACH, 17 vs. EXT, 16; p < 0.01). Despite a higher SSI rate (TRACH, 21% vs. INT, 13% vs. EXT, 2%; p = 0.11), the TRACH group had a lower mortality rate (TRACH, 0% vs. INT, 13% vs. EXT, 0%, p < 0.01) and more ventilator-free days compared with the INT cohort. On multivariate analysis, tracheostomy was associated with an increased risk in the odds of SSI (odds ratio, 9.56; 95% confidence interval, 1.35-67.95) compared with both EXT and INT, while INT was associated with fewer ventilator-free days (correlation coefficient, -9.24; 95% confidence interval, -12.30 to -6.18) compared with both EXT and TRACH. CONCLUSION: In patients with a cervical tracheal injury, immediate or early extubation was common and safe. However, among those with more severe injuries, immediate tracheostomy versus prolonged intubation presents a risk benefit decision. Immediate tracheostomy is associated with increased risk of SSI, while prolonged intubation is associated with higher risk of mortality and fewer ventilator-free days. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26670109 TI - Does enoxaparin interfere with HMGB1 signaling after TBI? A potential mechanism for reduced cerebral edema and neurologic recovery. AB - BACKGROUND: Enoxaparin (ENX) has been shown to reduce cerebral edema and improve neurologic recovery after traumatic brain injury (TBI), through blunting of cerebral leukocyte (LEU) recruitment. High mobility group box 1 (HMGB1) protein may induce inflammation through LEU activation. We hypothesized that ENX after TBI reduces LEU-mediated edema through blockade of HMGB1 signaling. METHODS: Twenty-three CD1 mice underwent severe TBI by controlled cortical impact and were randomized to one of four groups receiving either monoclonal antibody against HMGB1 (MAb) or isotype (Iso) and either ENX (1 mg/kg) or normal saline (NS): NS + Iso (n = 5), NS + MAb (n = 6), ENX + Iso (n = 6), ENX + MAb (n = 6). ENX or NS was administered 2, 8, 14, 23 and 32 hours after TBI. MAb or Iso (25 MUg) was administered 2 hours after TBI. At 48 hours, cerebral intravital microscopy served to visualize live LEU interacting with endothelium and microvascular fluorescein isothiocyanate-albumin leakage. The Neurological Severity Score (NSS) graded neurologic recovery; wet-to-dry ratios determined cerebral/lung edema. Analysis of variance with Bonferroni correction was used for statistical analyses. RESULTS: ENX and MAb similarly reduced in vivo pial LEU rolling without demonstrating additive effect. In vivo albumin leakage was greatest in vehicle treated animals but decreased by 25% with either MAb or ENX but by 50% when both were combined. Controlled cortical impact-induced cerebral wet-to-dry ratios were reduced by MAb or ENX without additive effect. Postinjury lung water was reduced by ENX but not by MAb. Neurologic recovery at 24 hours and 48 hours was similarly improved with ENX, MAb, or both treatments combined. CONCLUSION: Mirroring ENX, HMGB1 signaling blockade reduces LEU recruitment, cerebrovascular permeability, and cerebral edema following TBI. ENX further reduced lung edema indicating a multifaceted effect beyond HMGB1 blockade. Further study is needed to determine how ENX may play a role in blunting HMGB1 signaling in brain injury patients. PMID- 26670111 TI - Rhabdomyolysis among critically ill combat casualties: Associations with acute kidney injury and mortality. AB - BACKGROUND: Rhabdomyolysis has been associated with poor outcomes in patients with traumatic injury, especially in the setting of acute kidney injury (AKI). However, rhabdomyolysis has not been systematically examined in a large cohort of combat casualties injured in the wars in Iraq and Afghanistan. METHODS: We conducted a retrospective study of casualties injured during combat operations in Iraq and Afghanistan who were initially admitted to the intensive care unit from February 1, 2002, to February 1, 2011. Information on age, sex, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), mechanism of injury, shock index, creatine kinase, and serum creatinine were collected. These variables were examined via multivariate logistic and Cox regression analyses to determine factors independently associated with rhabdomyolysis, AKI, and death. RESULTS: Of 6,011 admissions identified, a total of 2,109 patients met inclusion criteria and were included for analysis. Rhabdomyolysis, defined as creatine kinase greater than 5,000 U/L, was present in 656 subjects (31.1%). Risk factors for rhabdomyolysis identified on multivariable analysis included injuries to the abdomen and extremities, increased ISS, male sex, explosive mechanism of injury, and shock index greater than 0.9. After adjustment, patients with rhabdomyolysis had a greater than twofold increase in the odds of AKI. In the analysis for mortality, rhabdomyolysis was significantly associated with death until AKI was added, at which point it lost statistical significance. CONCLUSION: We found that rhabdomyolysis is associated with the development of AKI in combat casualties. While rhabdomyolysis was strongly associated with mortality on the univariate model and in conjunction with both ISS and age, it was not associated with mortality after the inclusion of AKI. This suggests that the effect of rhabdomyolysis on mortality may be mediated by AKI. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26670112 TI - Image-based resuscitation of the hypotensive patient with cardiac ultrasound: An evidence-based review. AB - This article is a detailed review of the literature regarding the use of cardiac ultrasound for the resuscitation of hypotensive patients. In addition, figures regarding windows and description of how to perform the test are included. PMID- 26670114 TI - Extending the golden hour: Partial resuscitative endovascular balloon occlusion of the aorta in a highly lethal swine liver injury model. AB - BACKGROUND: Combat-injured patients may require rapid and sustained support during transport; however, the prolonged aortic occlusion produced by conventional resuscitative endovascular balloon occlusion of the aorta (REBOA) may lead to substantial morbidity. Partial REBOA (P-REBOA) may permit longer periods of occlusion by allowing some degree of distal perfusion. However, the ability of this procedure to limit exsanguination is unclear. We evaluated the impact of P-REBOA on immediate survival and ongoing hemorrhage in a highly lethal swine liver injury model. METHODS: Fifteen Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to rapid 10% total blood loss followed by 30% liver amputation. Coagulopathy was created through colloid hemodilution. Randomized swine received no intervention (control), P REBOA, or complete REBOA (C-REBOA). Central mean arterial pressure (cMAP), carotid blood flow, and blood loss were recorded. Balloons remained inflated in the P-REBOA and C-REBOA groups for 90 minutes followed by graded deflation. The study ended at 180 minutes from onset of hemorrhage or death of the animal. Survival analysis was performed, and data were analyzed using repeated-measures analysis of variance with post hoc pairwise comparisons. RESULTS: Mean survival times in the control, P-REBOA, and C-REBOA groups were, 25 +/- 21, 86 +/- 40, and 163 +/- 20 minutes, respectively (p < 0.001). Blood loss was greater in the P REBOA group than the C-REBOA or control groups, but this difference was not significant (4,722 +/- 224, 3,834 +/- 319, 3,818 +/- 37 mL, respectively, p = 0.10). P-REBOA resulted in maintenance of near-baseline carotid blood flow and cMAP, while C-REBOA generated extreme cMAP and prolonged supraphysiologic carotid blood flow. Both experimental groups experienced profound decreases in cMAP following balloon deflation. CONCLUSION: In the setting of severe ongoing hemorrhage, P-REBOA increased survival time beyond the golden hour while maintaining cMAP and carotid flow at physiologic levels. PMID- 26670113 TI - Outcomes and complications of angioembolization for hepatic trauma: A systematic review of the literature. AB - BACKGROUND: The liver is one of the most frequently injured abdominal organs. Hepatic hemorrhage is a complex and challenging complication following hepatic trauma. Significant shifts in the treatment of hepatic hemorrhage, including the increasing use of angioembolization, are believed to have improved patient outcomes. We aimed to describe the efficacy of angioembolization in the setting of acute hepatic arterial hemorrhage as well as the complications associated with this treatment modality. METHODS: A systematic review of published literature (MEDLINE, SCOPUS, and Cochrane Library) describing hepatic angioembolization in the setting of trauma was performed. Articles that fulfilled the predetermined inclusion and exclusion criteria were included. We analyzed the efficacy rate of angioembolization in the setting of traumatic hepatic hemorrhage as well as the complications associated with hepatic angioembolization. RESULTS: Four hundred fifty-nine articles were identified in the literature search. Of these, 10 retrospective studies and 1 prospective study met inclusion and exclusion criteria. Efficacy rate of angioembolization was 93%. The most frequently reported complications following hepatic angioembolization included hepatic necrosis (15%), abscess formation (7.5%), and bile leaks. CONCLUSION: Although the outcomes of hepatic angioembolization were generally favorable with a high success rate, the treatment modality is not without associated morbidity. The most frequently associated major complication was hepatic necrosis. Rates of complications were affected by study heterogeneity and should be better defined in future studies. LEVEL OF EVIDENCE: Systematic review, level III. PMID- 26670115 TI - Machine learning and new vital signs monitoring in civilian en route care: A systematic review of the literature and future implications for the military. AB - BACKGROUND: Although air transport medical services are today an integral part of trauma systems in most developed countries, to date, there are no reviews on recent innovations in civilian en route care. The purpose of this systematic review was to identify potential machine learning and new vital signs monitoring technologies in civilian en route care that could help close civilian and military capability gaps in monitoring and the early detection and treatment of various trauma injuries. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, and citation review of relevant primary and review articles were searched for studies involving civilian en route care, air medical transport, and technologies from January 2005 to November 2015. Data were abstracted on study design, population, year, sponsors, innovation category, details of technologies, and outcomes. RESULTS: Thirteen observational studies involving civilian medical transport met inclusion criteria. Studies either focused on machine learning and software algorithms (n = 5), new vital signs monitoring (n = 6), or both (n = 2). Innovations involved continuous digital acquisition of physiologic data and parameter extraction. Importantly, all studies (n = 13) demonstrated improved outcomes where applicable and potential use during civilian and military en route care. However, almost all studies required further validation in prospective and/or randomized controlled trials. CONCLUSION: Potential machine learning technologies and monitoring of novel vital signs such as heart rate variability and complexity in civilian en route care could help enhance en route care for our nation's war fighters. In a complex global environment, they could potentially fill capability gaps such as monitoring and the early detection and treatment of various trauma injuries. However, the impact of these innovations and technologies will require further validation before widespread acceptance and prehospital use. LEVEL OF EVIDENCE: Systematic review, level V. PMID- 26670117 TI - Anemia and iron-restricted erythropoiesis in traumatic critical illness. PMID- 26670116 TI - Multicenter validation of American Association for the Surgery of Trauma grading system for acute colonic diverticulitis and its use for emergency general surgery quality improvement program. AB - BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a new grading system for uniform description of anatomic severity of emergency general surgery (EGS) diseases, ranging from Grade I (mild) to Grade V (severe). The purpose of this study was to determine the relationship of AAST grades for acute colonic diverticulitis with patient outcomes. A secondary purpose was to propose an EGS quality improvement program using risk-adjusted center outcomes, similar to National Surgical Quality Improvement Program and Trauma Quality Improvement Program methodologies. METHODS: This was a retrospective study of 1,105 patients (one death) from 13 centers. At each center, two reviewers (blinded to each other's assignments) assigned AAST grades. Interrater reliability was measured using kappa coefficient. Relationship between AAST grade and clinical events (complications, intensive care unit use, surgical intervention, and 30-day readmission) as well as length of stay was measured using regression analyses to control for age, comorbidities, and physiologic status at the time of admission. Final model was also used to calculate observed to-expected (O-E) ratios for adverse outcomes (death, complications, readmissions) for each center. RESULTS: Median age was 54 years, 52% were males, 43% were minorities, and 22% required a surgical intervention. Almost two thirds had Grade I or II disease. There was a high level of agreement for grades between reviewers (kappa = 0.81). Adverse events increased from 13% for Grade I, to 18% for Grade II, 28% for Grade III, 44% for Grade IV, and 50% for Grade V. Regression analysis showed that higher disease grades were independently associated with all clinical events and length of stay, after adjusting for age, comorbidities, and physiology. O-E ratios showed statistically insignificant variations in risk of death, complications, or readmissions. CONCLUSION: AAST grades for acute colonic diverticulitis are independently associated with clinical outcomes and resource use. EGS quality improvement program methodology that incorporates AAST grade, age, comorbidities, and physiologic status may be used for measuring quality of EGS care. High-quality EGS registries are essential for developing meaningful quality metrics. LEVEL OF EVIDENCE: Prognostic study, level V. PMID- 26670118 TI - Knowledge gaps in the epidemiology of Toxocara: the enigma remains. AB - Toxocara species infect a wide range of companion, domestic and wild animals as definitive and paratenic hosts, via multiple routes of transmission, producing long-lived tissue-inhabiting larvae and resistant eggs that can survive in the external environment. Therefore Toxocara and the disease it causes in humans, toxocariasis, represents an ideal aetiological agent for the development of the one health approach. However, despite increasing awareness of the public health significance of toxocariasis, gaps in our understanding of certain key aspects of the parasite's biology and epidemiology remain. These gaps hinder our ability to integrate research effort within the veterinary, medical and environmental disciplines. This review will highlight key deficits in our understanding of nine dimensions of Toxocara epidemiology and discuss a potential scenario to develop a more integrated, one health approach to improve our understanding of the prevention and control of this complex and cryptic zoonosis. PMID- 26670119 TI - A systematic review of ultrasound-guided methods for brachial plexus blockade. AB - We systematically reviewed 25 randomised controlled trials of ultrasound-guided brachial plexus blockade that recruited 1948 participants: either one approach vs another (axillary, infraclavicular or supraclavicular); or one injection vs multiple injections. There were no differences in the rates of successful blockade with approach, relative risk (95% CI): axillary vs infraclavicular, 1.0 (1.0-1.1), p = 0.97; axillary vs supraclavicular, 1.0 (1.0-1.1), p = 0.68; and infraclavicular vs supraclavicular, 1.0 (1.0-1.1), p = 0.32. There was no difference in the rate of successful blockade with the number of injections, relative risk (95% CI) 1.0 (1.0-1.0), p = 0.69, for one vs multiple injections. The rate of procedural paraesthesia was less with one injection than multiple injections, relative risk (95% CI) 0.6 (0.4-0.9), p = 0.004. PMID- 26670120 TI - Intermittent Water Supply: Prevalence, Practice, and Microbial Water Quality. AB - Intermittent water supplies (IWS), in which water is provided through pipes for only limited durations, serve at least 300 million people around the world. However, providing water intermittently can compromise water quality in the distribution system. In IWS systems, the pipes do not supply water for periods of time, supply periods are shortened, and pipes experience regular flow restarting and draining. These unique behaviors affect distribution system water quality in ways that are different than during normal operations in continuous water supplies (CWS). A better understanding of the influence of IWS on mechanisms causing contamination can help lead to incremental steps that protect water quality and minimize health risks. This review examines the status and nature of IWS practices throughout the world, the evidence of the effect of IWS on water quality, and how the typical contexts in which IWS systems often exist-low-income countries with under-resourced utilities and inadequate sanitation infrastructure can exacerbate mechanisms causing contamination. We then highlight knowledge gaps for further research to improve our understanding of water quality in IWS. PMID- 26670121 TI - Non-sequential and multi-step splicing of the dystrophin transcript. AB - The dystrophin protein encoding DMD gene is the longest human gene. The 2.2 Mb long human dystrophin transcript takes 16 hours to be transcribed and is co transcriptionally spliced. It contains long introns (24 over 10kb long, 5 over 100kb long) and the heterogeneity in intron size makes it an ideal transcript to study different aspects of the human splicing process. Splicing is a complex process and much is unknown regarding the splicing of long introns in human genes. Here, we used ultra-deep transcript sequencing to characterize splicing of the dystrophin transcripts in 3 different human skeletal muscle cell lines, and explored the order of intron removal and multi-step splicing. Coverage and read pair analyses showed that around 40% of the introns were not always removed sequentially. Additionally, for the first time, we report that non-consecutive intron removal resulted in 3 or more joined exons which are flanked by unspliced introns and we defined these joined exons as an exon block. Lastly, computational and experimental data revealed that, for the majority of dystrophin introns, multistep splicing events are used to splice out a single intron. Overall, our data show for the first time in a human transcript, that multi-step intron removal is a general feature of mRNA splicing. PMID- 26670123 TI - Intellectual capital in the healthcare sector: a systematic review and critique of the literature. AB - BACKGROUND: Variations in the performance of healthcare organizations may be partly explained by differing "stocks" of intellectual capital (IC), and differing approaches and capacities for leveraging IC. This study synthesizes what is currently known about the conceptualization, management and measurement of IC in healthcare through a review of the literature. METHODS: Peer-reviewed papers on IC in healthcare published between 1990 and 2014 were identified through searches of five databases using the following key terms: intellectual capital/assets, knowledge capital/assets/resources, and intangible assets/resources. Articles deemed relevant for inclusion underwent systematic data extraction to identify overarching themes and were assessed for their methodological quality. RESULTS: Thirty-seven papers were included in the review. The primary research method used was cross-sectional questionnaires focused on hospital managers' perceptions of IC, followed by semi-structured interviews and analysis of administrative data. Empirical studies suggest that IC is linked to subjective process and performance indicators in healthcare organizations. Although the literature on IC in healthcare is growing, it is not advanced. In this paper, we identify and examine the conceptual, theoretical and methodological limitations of the literature. CONCLUSIONS: The concept and framework of IC offer a means to study the value of intangible resources in healthcare organizations, how to manage systematically these resources together, and their mutually enhancing interactions on performance. We offer several recommendations for future research. PMID- 26670124 TI - Thoughts from an old clinician: The well-intentioned stewards of the sword of Damocles. PMID- 26670122 TI - Comparative Transcriptome Analysis in the Hepatopancreas Tissue of Pacific White Shrimp Litopenaeus vannamei Fed Different Lipid Sources at Low Salinity. AB - RNA-seq was used to compare the transcriptomic response of hepatopancreas in juvenile Litopenaeus vannamei fed three diets with different lipid sources, including beef tallow (BT), fish oil (FO), and an equal combination of soybean oil + BT + linseed oil (SBL) for 8 weeks at 3 practical salinity unit (psu). A total of 9622 isogenes were annotated in 316 KEGG pathways and 39, 42 and 32 pathways significantly changed in the paired comparisons of FO vs SBL, BT vs SBL, or FO vs BT, respectively. The pathways of glycerolipid metabolism, linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, fatty acid biosynthesis, fatty acid elongation, fatty acid degradation, and biosynthesis of unsaturated fatty acid were significantly changed in all paired comparisons between dietary lipid sources, and the pathways of glycerolipid metabolism, linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism significantly changed in the FO vs SBL and BT vs SBL comparisons. These pathways are associated with energy metabolism and cell membrane structure. The results indicate that lipids sources affect the adaptation of L. vannamei to low salinity by providing extra energy or specific fatty acids to change gill membrane structure and control iron balance. The results of this study lay a foundation for further understanding lipid or fatty acid metabolism in L. vannamei at low salinity. PMID- 26670125 TI - Site-Resolved Two-Step Relaxation Process in an Asymmetric Dy2 Single-Molecule Magnet. AB - Elaborate chemical design is of utmost importance in order to slow down the relaxation dynamics in single-molecule magnets (SMMs) and hence improve their potential applications. Much interest was devoted to the study of distinct relaxation processes related to the different crystal fields of crystallographically independent lanthanide ions. However, the assignment of the relaxation processes to specific metal sites remains a challenging task. To address this challenge, a new asymmetric Dy2 SMM displaying a well-separated two step relaxation process with the anisotropic centers in fine-tuned local environments was elaborately designed. For the first time a one-to-one relationship between the metal sites and the relaxation processes was evidenced. This work sheds light on complex multiple relaxation and may direct the rational design of lanthanide SMMs with enhanced magnetic properties. PMID- 26670126 TI - Complex MAX Rearrangement in a Family With Malignant Pheochromocytoma, Renal Oncocytoma, and Erythrocytosis. AB - CONTEXT: Familial pheochromocytoma (PCC) has been associated with germline mutations in 16 genes. Here we investigated three siblings presenting with bilateral pheochromocytomas. In addition, the index patient also exhibited renal oncocytoma and erythrocytosis, whereas the second sibling presented with a lymph node metastasis. DESIGN: First, single-nucleotide polymorphism array and exome sequencing were performed on germline and PCC-derived DNA to identify genomic alterations in the index patient. Second, alterations were confirmed and validated by Sanger sequencing, analyzed by (multiplexed) PCR to determine the loss of the wild-type allele, and investigated by immunohistochemistry in the tumors of the three siblings. RESULTS: The index patient's germline DNA revealed a large complex genomic alteration encompassing the intragenic and promoter regions of Myc-associated factor X (MAX) and alpha-(1,6)-fucosyltransferase (FUT8). In all three siblings the MAX alteration was confirmed, and the loss of the wild-type MAX and FUT8 alleles was demonstrated in all tumors. Uniparental disomy of chromosome 14q, previously demonstrated as a hallmark for MAX-related PCC, was shown in the index patient's PCC by single-nucleotide polymorphism array. Loss of MAX and FUT8 protein expression was demonstrated by immunohistochemistry in the tumors from the three siblings. CONCLUSIONS: Our results indicate that large genomic deletions of MAX should be considered in familial and bilateral PCC with prior negative testing for gene mutations. In addition, our results confirm that MAX is a tumor suppressor gene for renal oncocytomas. PMID- 26670127 TI - Circulating Sex Hormones and Risk of Uterine Fibroids: Study of Women's Health Across the Nation (SWAN). AB - CONTEXT: Estrogen has been implicated in the development of uterine fibroids. However, the contribution of androgen in women is unknown. OBJECTIVE: Our objective was to assess the longitudinal relations of circulating androgens and estradiol (E2) and their joint effects to the risk of developing fibroids. DESIGN: This is a 13-year longitudinal study in the Study of Women's Health Across the Nation. SETTING: This study was conducted in seven sites across the United States (1997-2013). PARTICIPANTS: At baseline, 3240 pre- or early peri menopausal women with an intact uterus, ages 45-52 years were included; 43.6% completed the follow-up. There were 512 incident and 478 recurrent fibroid cases. EXPOSURES: We measured near-annual time-varying serum levels of bioavailable E2 and bioavailable T, dichotomized at the median (high vs low). MAIN OUTCOMES AND MEASURES: We estimated the conditional odds ratio (OR) of fibroids in the ensuing year using discrete-time proportional odds models adjusted for race/ethnicity/site, age, body mass index, menopausal stage, reproductive factors, smoking, timing of blood draw, and FSH. RESULTS: Women with high T had a statistically significant increased risk of incident fibroids (OR, 1.33; 95% confidence interval [CI], 1.01-1.76; P = .04), but not recurrent fibroids. This risk was further elevated in those with high T and E2 (OR, 1.52; 95% CI, 1.07 2.17; P = .02). High E2 and T was associated with lower risk of recurrent fibroids (OR, 0.50; 95% CI, 0.26-0.96; P = .04). CONCLUSIONS: High T with high E2 was associated with an elevated risk of incident fibroids in midlife women who never reported fibroids before baseline. Conversely, the risk of recurrent fibroids was mitigated in women with high E2 and high T. PMID- 26670128 TI - Associations of Body Mass Index With Incident Fractures and Hip Structural Parameters in a Large Canadian Cohort. AB - CONTEXT: Fractures in obese individuals are of public health importance, but the relationship between obesity and fracture is complex and remains poorly understood. OBJECTIVE: The study examined the association of body mass index (BMI) with bone structural and strength parameters and incident fracture. DESIGN AND SETTING: We performed cross-sectional and longitudinal analyses using data from the Manitoba Bone Density Program. PARTICIPANTS: We included 51 313 women and 4689 men aged 50 years or older referred for dual-energy X-ray absorptiometry scans. For 41 919 women and 4085 men, we were able to derive hip structural parameters. MAIN OUTCOME MEASURE: Cross-sectional moment of inertia, cross sectional area, and femoral strength index were derived from dual-energy X-ray absorptiometry. Health service records were assessed for incident major osteoporotic fractures (MOFs) (mean follow-up 6.2 y in women and 4.7 y in men). RESULTS: Among individuals with a BMI of less than 30 kg/m(2), increasing BMI was associated with progressive increases in bone mineral density (BMD), cross sectional moment of inertia, and cross-sectional area. The relationship reached a plateau around a BMI of 30 kg/m(2), with little additional increment with further increases in BMI (all P for interaction < .0001, obese vs nonobese). Increasing BMI was linearly associated with decreases in strength index in both women and men. MOFs were ascertained in 3721 women and 276 men (1027 female and 75 male hip fractures). Higher BMI was associated with a lower risk of MOF in women in multivariable models, but this association was largely explained by their higher BMD. Protective association of higher BMI with hip fracture were stronger and only partially explained by BMD (hazard ratio [95% confidence interval] 0.79 [0.73-0.99] for obese I and 0.67 [0.46-0.98] for obese II). Higher BMI was not significantly associated with a risk of MOF or hip fracture in men. CONCLUSIONS: Despite structural and biomechanical disadvantages, obese women were at lower risk of fracture. PMID- 26670129 TI - Eliciting patients' preferences for elastic compression stocking therapy after deep vein thrombosis: potential for improving compliance. AB - ESSENTIALS: Elastic compression stocking (ECS) therapy is used to prevent post thrombotic syndrome (PTS). We aimed to elicit patient preferences regarding ECS therapy after deep vein thrombosis. The most valued attributes were PTS risk reduction and the ability to put on the ECS independently. Heterogeneous results with respect to education level stress the importance of proper counselling. SUMMARY: BACKGROUND: Elastic compression stocking (ECS) therapy is used for prevention of post-thrombotic syndrome (PTS) after deep vein thrombosis (DVT). Current evidence on its effectiveness is conflicting. Compliance, a major determinant of the effectiveness of ECS therapy, remained largely ignored in former studies. OBJECTIVES: To gain insight into preferences regarding ECS therapy in patients after DVT. PATIENTS/METHODS: A discrete choice experiment was conducted 3 months after DVT in patients enrolled in the IDEAL DVT study, a randomized controlled trial comparing 2 years of ECS therapy with individually tailored duration of ECS therapy for the prevention of PTS. Nine unlabeled, forced-choice sets of two hypothetical types of ECS were presented to each patient. Data were analyzed with multinomial logit models. RESULTS: The respondent sample consisted of 81% (300/369) of invited patients. The most important determinants of preference were PTS risk reduction and putting on the ECS. Patients were willing to increase the duration of therapy by 1 year if this increases the PTS risk reduction with 10%. Patients accepted an increase in the risk of PTS of 29% if they were able to put on the ECS themselves. Preferences were heterogeneous with respect to education level. CONCLUSIONS: Reduction of the risk of PTS and the ability to put on the ECS without help are the most important characteristics of ECS therapy. Physicians should pay considerable attention to patient education regarding PTS. In addition, patients should be supported in their ability to put on and take off the ECS independently. These rather simple interventions could improve compliance. PMID- 26670130 TI - Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia. AB - Plasmid-based Sleeping Beauty (SB) transposon vectors were developed and used to deliver genes for low-density lipoprotein and very-low-density lipoprotein receptors (LDLR and VLDLR, respectively) or lacZ reporter into liver of an LDLR deficient mouse model of familial hypercholesterolemia (FH). SB transposase, SB100x, was used to integrate the therapeutic transposons into mice livers for evaluating the feasibility of the vectors in reducing high blood cholesterol and the progression of atherosclerosis. Hydrodynamic gene delivery of transposon VLDLR into the livers of the mice resulted in initial 17-19% reductions in plasma cholesterol, and at the later time points, in a significant stabilization of the cholesterol level for the 6.5-month duration of the study compared to the control mice. Transposon-LDLR-treated animals also demonstrated a trend of stabilization in the cholesterol levels in the long term. Vector-treated mice had slightly less lipid accumulation in the liver and reduced aortic atherosclerosis. Clinical chemistry and histological analyses revealed normal liver function and morphology comparable to that of the controls during the follow-up with no safety issues regarding the vector type, transgenes, or the gene transfer method. The study demonstrates the safety and potential benefits of the SB transposon vectors in the treatment of FH. PMID- 26670132 TI - The Psychometric Properties and the Development of the Indicators of Quality Nursing Work Environments in Taiwan. AB - BACKGROUND: The nursing shortage in medical institutions in Taiwan averaged 9% in 2012, considerably higher than the 5% indicated in the literature. As a result, many hospitals have been forced to close wards or reduce beds. Despite the acute need, the percentage of registered nurses who are employed as nurses in Taiwan (60.4%) is considerably lower than those in Canada or the United States. This low rate may be because of the poor working environment for nurses in Taiwan. PURPOSE: This study aimed to develop a set of nursing work environment quality indicators for Taiwan and to test the reliability and validity of the resulting survey tool. METHODS: Multiple methods were used in this study. In Phase 1, we organized an expert panel, reviewed the literature, and conducted seven rounds of expert panel discussion and six focus group discussions with nursing directors. The goal was to draft indicators representing a quality nursing work environment to fit current conditions in Taiwan. In Phase 2, we conducted an expert review for content validity, held three public hearings, and conducted a survey. Four hundred twenty-seven questionnaires were sent out, with 381 returned. The goal was to test the content validity, construct validity, and internal consistency reliability. RESULTS: The study produced a set of indicators of a quality nursing work environment with eight dimensions and 65 items. The content validity index for importance and suitability dimensions were 1.0, whereas the internal consistency was 0.91. The eight dimensions were safe practice environment (16 items), quality and quantity of staff (four items), salary and welfare (seven items), professional specialization and teamwork (seven items), work simplification (five items), informatics (five items), career development (nine items), and support and caring (12 items). The overall load for the indicators was 77.57%. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The developed indicators may be used to evaluate the quality of nursing work environments. Furthermore, the indicators may be used in hospital surveys to establish baseline conditions and for outcome research that measures improvement in nursing work environments after interventions. PMID- 26670131 TI - Efficient generation of region-specific forebrain neurons from human pluripotent stem cells under highly defined condition. AB - Human pluripotent stem cells (hPSCs) have potential to differentiate to unlimited number of neural cells, which provide powerful tools for neural regeneration. To date, most reported protocols were established with an animal feeder system. However, cells derived on this system are inappropriate for the translation to clinical applications because of the introduction of xenogenetic factors. In this study, we provided an optimized paradigm to generate region-specific forebrain neurons from hPSCs under a defined system. We assessed five conditions and found that a vitronectin-coated substrate was the most efficient method to differentiate hPSCs to neurons and astrocytes. More importantly, by applying different doses of purmorphamine, a small-molecule agonist of sonic hedgehog signaling, hPSCs were differentiated to different region-specific forebrain neuron subtypes, including glutamatergic neurons, striatal medium spiny neurons, and GABA interneurons. Our study offers a highly defined system without exogenetic factors to produce human neurons and astrocytes for translational medical studies, including cell therapy and stem cell-based drug discovery. PMID- 26670133 TI - The Outcome of Primary Subglandular Breast Augmentation Using Tumescent Local Anesthesia. AB - BACKGROUND: Tumescent local anesthesia (TLA) technique to obtain regional anesthesia and vasoconstriction of the skin and subcutaneous tissues is routinely adopted for several plastic surgery procedures. Here, we describe the use of TLA in primary subglandular breast augmentation. This series evaluates advantages and disadvantages of TLA in elective augmentation breast surgery as well as patients' response to this procedure. METHODS: Between December 2008 and November 2011, 150 patients underwent bilateral primary subglandular breast augmentation under TLA and conscious sedation in the presence of a board-certified anesthesiologist. Midazolam 0.05 mg/kg IV and ranitidine 100 mg IV were given as premedication. Tumescent local anesthesia was composed of 25 mL of lidocaine 2%, 8 mEq of sodium bicarbonate, and 1 mL of epinephrine (1 mg/1 mL) in 1000 mL of 0.9% NS. The solution was delivered between the pectoral fascia and the mammary gland via a spinal needle. After infiltration, 45 minutes were allowed before surgery for local anesthetic effects to take place. RESULTS: The mean age of the patients was 34.3 years. The average amount of tumescent solution infiltrated was 1150 mL, with a maximal dose of 17 mg/kg of lidocaine used. Operating time was 45 minutes and recovery room time averaged 125 minutes. Minor complications were found in a total of 9 (5.3%) patients, with no main surgery-related complications such as hematoma or seroma formation. CONCLUSIONS: Breast augmentation under TLA and conscious sedation proved to be safe in the presence of a board-certified anesthesiologist and when performed with meticulous surgical technique. PMID- 26670134 TI - A Cohort Analysis of Postbariatric Panniculectomy--Current Trends in Surgeon Reimbursement. AB - BACKGROUND: The overall number of patients undergoing body contouring procedures after massive weight loss (MWL) has progressively increased over the past decade. The purpose of this study was to evaluate the charges and reimbursements for panniculectomy after MWL at a large academic institution in Massachusetts. METHODS: A retrospective review was performed and included all identifiable panniculectomy procedures performed at our institution between January 2008 and January 2014. The annual number of patients undergoing panniculectomy, the type of insurance coverage and reimbursement method of each patient, and the amounts billed and reimbursed were evaluated. RESULTS: During our study period, 114 patients underwent a medically necessary panniculectomy as a result of MWL. The average surgeon fee billed was $3496 +/- $704 and the average amount reimbursed was $1271 +/- $589. Ten cases (8.8%) had no reimbursements, 31 cases (21.8%) reimbursed less than $1000, 66 cases (57.9%) reimbursed between $1000 and $2000, and no cases reimbursed the full amount billed. When evaluated by type of insurance coverage, collection ratios were 37.4% +/- 17.4% overall, 41.7% +/- 16.4% for private insurance, and 24.0% +/- 13.0% for Medicare/Medicaid insurance (P < 0.001). CONCLUSIONS: Reimbursements for panniculectomy are remarkably low, and in many instances, absent, despite obtaining previous preauthorization of medical necessity. Although panniculectomy is associated with improvements in quality of life and high levels of patient satisfaction, poor physician reimbursement for this labor intensive procedure may preclude access to appropriate care required by the MWL patient population. PMID- 26670136 TI - Graphene oxide as a metal-free catalyst for oxidation of primary amines to nitriles by hypochlorite. AB - Graphene oxide catalyzes oxidation by NaClO of primary benzyl and aliphatic amines to a product distribution comprising nitriles and imines. Nitriles are the sole product for long chain aliphatic amines. Spectroscopic characterization suggests that percarboxylic and perlactone groups could be the active sites of the process. PMID- 26670135 TI - RNA-sequencing Reveals Global Transcriptomic Changes in Nicotiana tabacum Responding to Topping and Treatment of Axillary-shoot Control Chemicals. AB - Removal of terminal buds (topping) and control of the formation of axillary shoots (suckers) are common agronomic practices that significantly impact the yield and quality of various crop plants. Application of chemicals (suckercides) to plants following topping is an effective method for sucker control. However, our current knowledge of the influence of topping, and subsequent suckercide applications, to gene expression is limited. We analyzed the differential gene expression using RNA-sequencing in tobacco (Nicotiana tabacum) that are topped, or treated after topping by two different suckercides, the contact-localized systemic, Flupro((r)) (FP), and contact, Off-Shoot-T((r)). Among the differentially expressed genes (DEGs), 179 were identified as common to all three conditions. DEGs, largely related to wounding, phytohormone metabolism and secondary metabolite biosynthesis, exhibited significant upregulation following topping, and downregulation after suckercide treatments. DEGs related to photosynthetic processes were repressed following topping and suckercide treatments. Moreover, topping and FP-treatment affect the expression of auxin and cytokinin signaling pathway genes that are possibly involved in axillary shoot formation. Our results provide insights into the global change of plant gene expression in response to topping and suckercide treatments. The regulatory elements of topping-inducible genes are potentially useful for the development of a chemical-free sucker control system. PMID- 26670137 TI - Trends in the histopathology of childhood nephrotic syndrome in Ibadan Nigeria: preponderance of idiopathic focal segmental glomerulosclerosis. AB - BACKGROUND: Reports on the histopathology of childhood nephrotic syndrome (NS) had emanated from our Centre since the 1960s and by the late 1980s and early 1990s, a change was observed and reported. Taking into consideration the worldwide changing trend in the histopathology of the NS and our Unit policy change in the indications for renal biopsy, a change was envisaged. We therefore evaluated the current histologic pattern of childhood NS in Ibadan with the view to highlighting any variations from the past and comparing the findings with regional and global trends. METHODOLOGY: We reviewed our database and analyzed the renal biopsy findings in patients who were biopsied before treatment was administered between 1997 and 2001 and those with mostly idiopathic steroid resistant NS (SRNS) and secondary NS, managed between 2006 and 2013. A comparative analysis of the findings from the present study was carried out with two previous reports from our Unit in the 1970s and early 1990s and also with reports from other Centres. RESULTS: A total of 78 patients had successful biopsies done during the study period in children aged between 2 1/2 and 16 years. In both pre-treatment biopsy era (1997-2001) and post-treatment biopsy era (2006-2013), focal segmental glomerulosclerosis (FSGS) predominated. 75 % of the patients had idiopathic NS and among the patients that had idiopathic steroid resistant NS, FSGS was the most common followed by MPGN. For secondary NS, MCD was the most common but could be the early stages of either membranous nephropathy (MN) or FSGS. Chronic pyelonephritis and chronic interstitial nephritis occurred in 25 % of the study population but they were more prevalent in secondary nephrotic syndrome. CONCLUSION: FSGS is the most common histopathology in children requiring renal biopsy in Ibadan presently. FSGS is also the most common histopathology in idiopathic SRNS, which is in keeping with reports from most parts of the world. There has been a transition from the preponderance of Quartan Malarial Nephropathy (QMN) in the 1960s to MPGN in the 1980s to FSGS presently. This has great implications with regards to searching for new aetiologic factors, providing more efficacious treatment modalities and ensuring facilities for immunofluorescence, electron microscopic and genetic studies. PMID- 26670138 TI - Space-charge Effect on Electroresistance in Metal-Ferroelectric-Metal capacitors. AB - Resistive switching through electroresistance (ER) effect in metal-ferroelectric metal (MFM) capacitors has attracted increasing interest due to its potential applications as memories and logic devices. However, the detailed electronic mechanisms resulting in large ER when polarisation switching occurs in the ferroelectric barrier are still not well understood. Here, ER effect up to 1000% at room temperature is demonstrated in C-MOS compatible MFM nanocapacitors with a 8.8 nm-thick poly(vinylidene fluoride) (PVDF) homopolymer ferroelectric, which is very promising for silicon industry integration. Most remarkably, using theory developed for metal-semiconductor rectifying contacts, we derive an analytical expression for the variation of interfacial barrier heights due to space-charge effect that can interpret the observed ER response. We extend this space-charge model, related to the release of trapped charges by defects, to MFM structures made of ferroelectric oxides. This space-charge model provides a simple and straightforward tool to understand recent unusual reports. Finally, this work suggests that defect-engineering could be an original and efficient route for tuning the space-charge effect and thus the ER performances in future electronic devices. PMID- 26670139 TI - Lacritin Salvages Human Corneal Epithelial Cells from Lipopolysaccharide Induced Cell Death. AB - Innate immunity of the corneal epithelium is conferred by proteinaceous secretions from the epithelium and associated lacrimal and meibomian glands. Lacritin, an eye-specific protein with anti-microbial, cytoprotective and wound healing properties, predominantly secreted by lacrimal glands, is absent in conditions such as Dry eye and Keratitis. In view of the biological significance of lacritin in human eye, we investigated its role in human corneal epithelial (HCE) cells during lipopolysaccharide (LPS)-induced infection. LPS-challenged HCE cells demonstrated apoptosis-mediated cell death and elevated lacritin levels. The LPS-induced cell death is alleviated with exogenous supplementation of recombinant lacritin. This cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2). This study is the first to highlight the protective role of lacritin and mechanism of its action during bacterial infection of cornea in vitro. PMID- 26670140 TI - Normative Thyroid-Stimulating Hormone Values for Healthy Nigerian Newborns. AB - BACKGROUND: Congenital hypothyroidism is a common congenital endocrine disorder prevailing all over the world. No nationwide screening exists for any sub-Saharan country. We present normative cord and capillary thyroid-stimulating hormone (TSH) values for healthy Nigerian newborns. SUBJECTS AND METHODS: A cross sectional study was carried out in 6 university hospitals in Nigeria between January 1 and December 31, 2013. Cord and heel blood placed on 4 concentric circles on a Whartman filter paper were analysed for TSH within 1 week of collection using AutoDelfia 1235 immunoassay (Perkin Elmer Wallace, Boston, Mass., USA) at Charite - Universitatsmedizin Berlin, Berlin, Germany. The mean TSH levels of the newborns were determined, considering their sex, birthweight, socioeconomic status, and birth city. The association between the mean TSH level and other parameters was determined by analysis of variance. RESULTS: A total of 2,014 subjects were recruited during the study period. The mean TSH value for the subjects was 1.86 MUIU/ml, and 98.1% of the newborns were within the 2.5th and 97.5th percentiles (range: 0.09-7.90 MUIU/ml) of the TSH levels. We collected 247 cord and 1,767 heel samples, respectively, and the range was slightly higher in samples from cord blood. CONCLUSION: The study highlights the normal reference values for capillary/cord TSH levels in term Nigerian newborns. TSH was higher in one region, attributable to earlier sampling, but was not influenced by gender, socioeconomic status, or birthweight. PMID- 26670141 TI - [Not Available]. PMID- 26670142 TI - [Not Available]. PMID- 26670143 TI - [Not Available]. PMID- 26670144 TI - [Not Available]. PMID- 26670145 TI - [Not Available]. PMID- 26670146 TI - [Orthotic Supply after Complex Trauma of the Foot]. AB - BACKGROUND: After complex trauma of the foot, patients frequently need orthotic care. There have been no systematic studies on the quality of care or patient satisfaction. Therefore the goal of this study was to evaluate patient satisfaction and the quality of orthotic care. PATIENT AND METHODS: In a prospective non-randomized, cross-sectional intervention study, the quality of care and patient satisfaction with orthotic devices were evaluated clinically and pedographically. This was followed by a lengthy discussion and recommendation to improve the insoles or shoes. These improvements were followed up by a written/telephone survey. 39 of the 50 recruited patients with complex trauma of the foot (78 %) were supplied with orthotic devices (insoles, modifications of the sole and orthopaedic shoes). RESULTS AND CONCLUSION: Most patients (76 %) were content with their orthotic care. However, shortcomings were noted in 20 patients. These were: insufficient arch support/stabilization, inadequate support of roll-off and unsatisfactory unloading of the forefoot. 23 % of the patients did not use their orthotic devices. Compliance increased after counseling. However, half of the patients had problems in obtaining reimbursement for the modifications recommended. In conclusion, orthotic treatment of patients after complex trauma of the foot is demanding. Modifications of the devices are frequently needed. Interprofessional collaboration plays an important role. PMID- 26670147 TI - [Air Entrapment Caused by Valve Mechanisms in Chronic Wounds, a Benign Phenomenon? A Series of Three Cases]. AB - BACKGROUND: Benign subcutaneous emphysema caused by a valve mechanism and subsequent air entrapment is rare. Less invasive treatment can be performed, but acute life-threatening infectious diseases should be ruled out before treatment; these include gas gangrene or other infections caused by gas producing bacteria. PATIENTS AND METHODS: We retrospectively report on three patients with chronic wounds who developed benign subcutaneous extremity emphysema caused by valve mechanisms with subsequent air entrapment. Patient 1 had a chronic wound at his stump after a lower leg amputation years ago. Due to weight loading and unloading of the lower leg prosthesis while walking, air was sucked in and triggered subcutaneous emphysema. Patient 2 had a persistent fistula at his lateral thigh due to a chronic osteomyelitis and Girdlestone hip. Caused by the up-and-down movements of the femur during walking air was entrapped and led to emphysema. Patient 3 had a drain in his knee for development of a chronic fistula because of a persistent infection of his knee prosthesis. In extension of the knee, the drain was clamped in and air was entrapped during knee flexion and then seeped into the surrounding subcutaneous tissue. No signs of infection in the blood samples were present in two of the patients. None of the patients had fever and no gas producing bacteria were identified in the microbiological cultures. Only multisensitive Staphylococcus aureus was present in the wounds of patients 1 and 2. RESULTS: Two patients were treated surgically. One patient was treated by fasciotomy plus debridement and irrigation of the wound. A second patient was treated by debridement of the Girdlestone hip, air evacuation and insertion of a drain. No sign of infection - such as necrosis or gangreneous tissue - was seen during these operations. In patient 3, the drain was removed in flexion of the knee and air was removed from the subcutaneous tissue through a separate, sterile needle punction. CONCLUSION: There have been few published reports on benign subcutaneous emphysema caused by a valve mechanism. No standardised treatments exist, as it is initially difficult to distinguish this condition from an acute life-threatening infection. If a patient has a chronic wound at the location of the endoprosthesis or stump prosthesis after amputation, the possibility of benign air entrapment should be routinely considered. PMID- 26670148 TI - [Radial Head Replacement - Surgical Technique and Own Clinical Results]. AB - BACKGROUND: Radial head arthroplasty is an established method to restore the anatomy and biomechanics of the elbow joint - especially for non-reconstructable radial head fractures. AIMS: This video article aims to explain the indications, the surgical procedure and the postoperative rehabilitation protocol for radial head replacement. We also present our own results with this procedure. MATERIAL AND METHODS: Since 2014, we have prospectively evaluated all patients undergoing surgery for radial head replacement (MoPyC, Tornier, France). A 6 month follow-up of 11 patients is now available. Moreover, 3 retrospective cases with rare complications are reported which were not part of our prospective evaluation. RESULTS: 8 of 11 procedures were performed due to acute, non-reconstructable radial head fractures. Secondary radial head replacement as a result of failed osteosynthesis was performed in the remaining 3 cases. 8 patients had clinically relevant concomitant injuries to the elbow joint. The mean Mayo Elbow Performance Score was 88 points (65 to 100 points). The arc of motion averaged 124 degrees (+/- 18 degrees ). At 6 months, the mean extension lag was 8 degrees . There were no complications requiring revision surgery at 6 months. Retrospective evaluation found one patient with extensive osteolysis due to oversizing of the shaft, one with disconnection of the prosthesis and one with a broken prosthesis shaft. CONCLUSIONS: The clinical results with radial head arthroplasty are promising. Accurate implantation is crucial to minimise the risk of complications requiring revision surgery. PMID- 26670149 TI - [Analysis of the Picture 1 a and 1 b]. PMID- 26670150 TI - [Not Available]. PMID- 26670151 TI - [Long Bone Nonunion]. AB - The percentage of delayed or non-unions after fractures of long bones depends on the individual risk profile at approximately 10 %. The current definition states that a non-union is a fracture that will not consolidate without any further intervention - independent from the treatment time. At the early stage of a non union a conservative treatment is possible in case of an adequately stable situation. The operative treatment depends on the type of the non-union. There are one-step or two-step procedures, all according to the principles of the "diamond concept". This means improvement of the mechanical situation - in most cases by means of a reosteosynthesis - and vascularization, local application of osteoconductive carriers e.g. tricalciumphosphate, vital cells from autologous bone and osteoinductive substances like bone morphogenetic proteins (BMP-2 or BMP 7). Hypertrophic and atrophic non-unions without large defect gaps or signs of infection can be treated with a one-step procedure. For treating infected non unions or non-unions with large defect gaps the Masquelet technique is recommended. PMID- 26670152 TI - Frequency of Plasmid-Mediated AmpC beta-Lactamases in Escherichia coli Isolates from Urine Samples in Sao Paulo, Brazil. AB - Plasmid-mediated AmpC beta-lactamases (PMACBLs) in Enterobacteriaceae encode resistance to third-generation cephalosporins, and these can mediate carbapenem resistance when associated with porin loss. However, no standardized phenotypic method is available for detecting these enzymes in the clinical microbiology laboratory. Limited data are available concerning the frequency of PMACBLs in Enterobacteriaceae in Brazil. This study was conducted in response to an increased cefoxitin (CFO) resistance rate of 3.7% in Escherichia coli isolates from urine samples from patients with suspected urinary tract infections during 2010. We collected 2,266 E. coli isolates prospectively during January 2012. A total of 109 (4.8%) isolates were nonsusceptible to CFO. These strains were further examined using multiplex PCR for the presence of genes encoding PMACBLs and using inhibitor assays with CFO and ceftazidime (CAZ) disks with and without phenylboronic acid. Pulsed-field gel electrophoresis was used to evaluate clonal dissemination. Genes encoding PMACBLs were detected in 1.8% of the isolates from inpatients and 0.46% of isolates from outpatients. The most prevalent gene was blaCMY-2 and blaCMY-4 was also detected. The phenotypic analysis showed 100% sensitivity and specificity for CMY-2 and CMY-4 when CFO-resistant isolates with a minimum zone diameter difference of 5 mm for CAZ or CAZ and CFO were considered positive. Although most of the isolates were nonclonal, one clonal group with two isolates was observed. Thus, the most frequent PMACBL in E. coli from Sao Paulo, Brazil is CMY-2, and both clonal and plasmid-mediated dissemination occur. PMID- 26670153 TI - Measuring behaviours for escaping from house fires: use of latent variable models to summarise multiple behaviours. AB - BACKGROUND: This paper reports the development and testing of a construct measuring parental fire safety behaviours for planning escape from a house fire. METHODS: Latent variable modelling of data on parental-reported fire safety behaviours and plans for escaping from a house fire and multivariable logistic regression to quantify the association between groups defined by the latent variable modelling and parental-report of having a plan for escaping from a house fire. Data comes from 1112 participants in a cluster randomised controlled trial set in children's centres in 4 study centres in the UK. RESULTS: A two class model provided the best fit to the data, combining responses to five fire safety planning behaviours. The first group ('more behaviours for escaping from a house fire') comprised 86% of participants who were most likely to have a torch, be aware of how their smoke alarm sounds, to have external door and window keys accessible, and exits clear. The second group ('fewer behaviours for escaping from a house fire') comprised 14% of participants who were less likely to report these five behaviours. After adjusting for potential confounders, participants allocated to the 'more behaviours for escaping from a house fire group were 2.5 times more likely to report having an escape plan (OR 2.48; 95% CI 1.59-3.86) than those in the "fewer behaviours for escaping from a house fire" group. CONCLUSIONS: Multiple fire safety behaviour questions can be combined into a single binary summary measure of fire safety behaviours for escaping from a house fire. Our findings will be useful to future studies wishing to use a single measure of fire safety planning behaviour as measures of outcome or exposure. TRIAL REGISTRATION NUMBER: NCT 01452191. Date of registration 13/10/2011. PMID- 26670154 TI - Comparing the diagnostic utility of sacroiliac spectral CT and MRI in axial spondyloarthritis. AB - OBJECTIVE: To compare the clinical value of sacroiliac spectral CT and MRI in diagnosing axial spondyloarthritis (SpA). METHODS: 137 patients with low back pain and suspected axial SpA were recruited. 76 patients were diagnosed with axial SpA, and 49 patients were diagnosed with non-specific low back pain (nLBP). Each patient underwent spectral CT and MRI examinations of the sacroiliac joints. Water- and calcium-based material decomposition images were reconstructed for quantitative analysis. The marrow-to-muscle ratios of water and calcium concentrations and short tau inversion recovery (STIR) signal intensity, as well as Hounsfield units in the ilium and sacrum were compared between nLBP and patients with axial SpA. RESULTS: Spectral CT is comparable with MRI for the detection of bone marrow oedema, and it is superior to MRI for detection of osseous sclerosis and erosions. MRI is superior to spectral CT in detecting enthesitis and synovitis. There were statistically significant differences in STIR signal intensity, water concentration and calcium concentration ratios as well as CT values between nLBP and patients with axial SpA (p < 0.05) in the ilium. There was a statistically significant but weak correlation between ratios of water concentration and STIR signal intensity in both the ilium and sacrum (p < 0.05). Overall, the iliac water concentration was most sensitive for detection of patients with SpA. The positive likelihood ratio of the STIR signal intensity ratio was the highest. The diagnostic odds ratio of the calcium concentration ratio was the highest, and its negative likelihood ratio was the lowest. CONCLUSION: Spectral CT not only depicts findings of chronic sacroiliitis (i.e. bone erosion and sclerosis), but also can detect and quantify the extent of marrow oedema in patients with SpA with activity sacroiliitis. The sensitivity of MRI for diagnosis of early synovitis and enthesitis remains superior. The combination of spectral CT and MRI may thus improve diagnostic accuracy in the diagnosis of axial SpA. ADVANCES IN KNOWLEDGE: Spectral CT can measure both calcium and water concentration of the sacroiliac joints. The combination of spectral CT and MRI may thus improve diagnostic accuracy in the diagnosis of axial SpA. PMID- 26670155 TI - Thoracolumbar junction: morphologic characteristics, various variants and significance. AB - OBJECTIVE: This study aimed to assess the types of vertebral segments at the thoracolumbar junction, as they relate to the most caudal ribs, to evaluate the reliability of this assessment using axial CT with curved planar reformatting (CPR) images, to describe the morphologic characteristics of a thoracolumbar transitional vertebra (TLTV), to introduce a new classification system for the TLTV and to evaluate the reliability of the classification system using axial CT with CPR images. METHODS: This was a retrospective review of 744 consecutive patients who underwent spine CT imaging that included the thoracolumbar junction. Two radiologists (Readers 1 and 2) independently evaluated the axial CT with CPR images for all cases (n = 744). Each radiologist differentiated the vertebral segments at the thoracolumbar junction as TLTV or non-TLTV (thoracic segment or lumbar segment). In addition, each radiologist classified the 94 patients with the TLTV using a novel classification system. Interobserver agreement between the two radiologists regarding the differentiation of vertebral segments at the thoracolumbar junction was analysed with kappa statistics. Similarly, intra- and interobserver agreement regarding TLTV classification was analysed with kappa statistics. RESULTS: Interobserver agreement between the two readers with respect to the differentiation of vertebral segments at the thoracolumbar junction via axial CT with CPR images was nearly perfect (kappa-value: 0.959). Interobserver agreement between the two readers with respect to TLTV classification using axial CT with CPR images was nearly perfect (kappa-value: 0.846). In addition, intraobserver agreement for Reader 1 was also nearly perfect (kappa-value: 0.877). CONCLUSION: Morphologic analysis of the thoracolumbar junction may help accurate spinal enumeration. ADVANCES IN KNOWLEDGE: Consideration of various variants at the thoracolumbar junction should help radiologists and clinicians to interpret the morphology of the thoracolumbar junction. This may facilitate communication with the referring clinician, thereby reducing the error in spinal enumeration. PMID- 26670156 TI - Diagnostic accuracy of standard axial 64-slice chest CT compared to cardiac MRI for the detection of cardiomyopathies. AB - OBJECTIVE: To assess the diagnostic accuracy of standard axial chest CT compared with cardiac MRI for cardiomyopathies. METHODS: The standard axial 64-slice chest CTs of 49 patients with cardiomyopathies and 27 controls were blindly assessed for the presence of a cardiomyopathy by two independent readers. Qualitative and quantitative analysis included assessment of: (i) interatrial septal thickness, (ii) left atrial diameter, (iii) myocardial hypertrophy, thinning or fat, (iv) myocardial and papillary muscle calcification, (v) papillary muscle thickness, (vi) calcified coronary artery segments, (vii) left ventricular (LV) diameter, (viii) interventricular septal thickness and (ix) right ventricular diameters. Cardiac MRI was the gold standard. RESULTS: There were 21 (42.9%) dilated, 16 (32.7%) hypertrophic, 8 (16.3%) ischaemic and 4 other (8.2%) (LV non-compaction * 2, amyloid, idiopathic restrictive) patients with cardiomyopathies. An LV diameter of 47 mm, interventricular septal thickness of 14 mm and coronary artery/papillary muscle calcification on axial chest CT best distinguished dilated, hypertrophic and ischaemic cardiomyopathies from controls, respectively; kappa = 0.45 (moderate interobserver agreement). The sensitivity (95% confidence interval), specificity, positive- and negative-predictive values (95% confidence interval) and diagnostic accuracy of chest CT in diagnosing cardiomyopathies were 68% (52-83), 100%, 100%, 66% (55-85) and 80%, respectively. CONCLUSION: Cardiomyopathies may be detected on standard chest CT with good sensitivity and high specificity. ADVANCES IN KNOWLEDGE: It is useful to assess for an underlying cardiomyopathy on standard chest CT, especially in a patient with unexplained dyspnoea. PMID- 26670157 TI - Unusual childhood presentations of abdominal non-Hodgkin's lymphoma. AB - Non-Hodgkin's lymphoma (NHL) is a relatively common childhood cancer that can present in a myriad of ways. It is essential that NHL is included in the differential diagnosis of children presenting with an abdominal complaint, especially those with unexplained or prolonged symptoms. We describe three acute pediatric presentations of abdominal NHL, two of which presented as acute abdomen (the first mimicking intussusception and the second appendicitis), and the third involving lower limb edema. This case series illustrates the array of presentations of abdominal NHL and the diagnostic challenges that they can provide. PMID- 26670158 TI - Intravascular large B-cell lymphoma involving gastrointestinal stromal tumor: a case report and literature review. AB - BACKGROUND: Intravascular large B-cell lymphoma is a rare and aggressive lymphoma with a dismal prognosis. Synchronous intravascular large B-cell lymphoma involving gastrointestinal stromal tumor has not previously been documented. CASE PRESENTATION: We report a case of a 61-year-old Chinese woman who presented with high fever of unknown origin for 20 days, and hematemesis, melena for 2 days. A computed tomography scan revealed a mass lesion located in the anterior wall of the stomach. Surgery was performed to remove the tumor and histopathology showed a gastrointestinal stromal tumor and a synchronous intravascular large B-cell lymphoma. The patient refused further treatment and died 4 months after surgery. CONCLUSIONS: To the best of our knowledge, this case represents the first report of synchronous intravascular large B-cell lymphoma involving a gastrointestinal stromal tumor. PMID- 26670159 TI - Hot pot burns and the dangers of portable gas stove. PMID- 26670160 TI - Epidemiology and financial implications of self-inflicted burns. AB - INTRODUCTION: The cost of the treatment of burns is high especially in self inflicted burns with prolonged treatment. We performed a retrospective review of the self-inflicted burns at our regional burns centre to determine the costs incurred in their management and to identify factors which could reduce the financial burden in the future. METHODS: The data was collected retrospectively of all the inpatient and outpatient self-inflicted burns presenting to our regional burns centre in the year 2011. RESULTS: Twenty one patients (out of a total of 870 patients) presented with self-inflicted burns to our centre in 2011. Five (23.8%) were major burns with an average of 53.2% Total Body Surface Area (TBSA) and 16 (76.2%) were minor burns with an average of 0.5% TBSA. 11 (52.4%) patients had flame burns including 4 self-immolation burns. The mortality rate was 4.8% (n=1). Five (23.8%) patients underwent surgical treatment. Seven (33.3%) patients were treated in intensive care and with average stay of 46.85 days. Critical care and theatre attendances made up most of the costs with average ICU stay per patient calculated at L313,131/day. The total cost of all 21 patients was L1,581,856. CONCLUSION: Burns are preventable injuries, early detection and intervention in patients with propensity to self-inflict burns can possibly reduce the costs of treatment in the future. PMID- 26670162 TI - The cost-effectiveness of screening for gestational diabetes mellitus in primary and secondary care in the Republic of Ireland. AB - AIMS/HYPOTHESIS: The aim of the study was to assess the cost-effectiveness of screening for gestational diabetes mellitus (GDM) in primary and secondary care settings, compared with a no-screening option, in the Republic of Ireland. METHODS: The analysis was based on a decision-tree model of alternative screening strategies in primary and secondary care settings. It synthesised data generated from a randomised controlled trial (screening uptake) and from the literature. Costs included those relating to GDM screening and treatment, and the care of adverse outcomes. Effects were assessed in terms of quality-adjusted life years (QALYs). The impact of the parameter uncertainty was assessed in a range of sensitivity analyses. RESULTS: Screening in either setting was found to be superior to no screening, i.e. it provided for QALY gains and cost savings. Screening in secondary care was found to be superior to screening in primary care, providing for modest QALY gains of 0.0006 and a saving of ?21.43 per screened case. The conclusion held with high certainty across the range of ceiling ratios from zero to ?100,000 per QALY and across a plausible range of input parameters. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that implementation of universal screening is cost-effective. This is an argument in favour of introducing a properly designed and funded national programme of screening for GDM, although affordability remains to be assessed. In the current environment, screening for GDM in secondary care settings appears to be the better solution in consideration of cost-effectiveness. PMID- 26670164 TI - Computational Design of a Family of Light-Driven Rotary Molecular Motors with Improved Quantum Efficiency. AB - Two new light-driven molecular rotary motors based on the N-alkylated indanylidene benzopyrrole frameworks are proposed and studied using quantum chemical calculations and nonadiabatic molecular dynamics simulations. These new motors perform pure axial rotation, and the photochemical steps of the rotary cycle are dominated by the fast bond-length-alternation motion that enables ultrafast access to the S1/S0 intersection. The new motors are predicted to display a quantum efficiency higher than that of the currently available synthetic all-hydrocarbon motors. Remarkably, the quantum efficiency is not governed by the topography (peaked versus sloped) of the minimum-energy conical intersection, whereas the S1 decay time depends on the topography as well as on the energy of the intersection relative to the S1 minimum. It is the axial chirality (helicity), rather than the point chirality, that controls the sense of rotation of the motor. PMID- 26670163 TI - Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians. AB - AIMS/HYPOTHESIS: Epidemiological studies in Pima Indians identified elevated levels of HDL-cholesterol (HDL-C) as a protective factor against type 2 diabetes risk in women. We assessed whether HDL-C-associated single-nucleotide polymorphisms (SNPs) also associate with type 2 diabetes in female Pima Indians. METHODS: Twenty-one SNPs in established HDL-C loci were initially analysed in 2,675 full-heritage Pima Indians. SNPs shown to associate with HDL-C (12 SNPs) were assessed for association with type 2 diabetes in 7,710 Pima Indians (55.6% female sex). The CETP locus provided the strongest evidence for association with HDL-C and was further interrogated by analysing tag SNPs. RESULTS: Twelve of the 21 SNPs analysed had a significant association with HDL-C in Pima Indians; five SNPs representing four loci (CETP, DOCK6, PPP1R3B and ABCA1) reached genome-wide significance. Three SNPs, at CETP, KLF14 and HNF4A, associated with type 2 diabetes only in female participants with the HDL-C-lowering allele increasing diabetes risk (p values: 3.2 * 10(-4) to 7.7 * 10(-5)); the association remained significant even after adjustment for HDL-C. Additional analysis across CETP identified rs6499863 as having the strongest association with type 2 diabetes in female participants (p = 5.0 * 10(-6)) and this association remained independent of the HDL-C association. CONCLUSIONS/INTERPRETATION: SNPs at the CETP, HNF4A and KLF14 locus are associated with HDL-C levels and type 2 diabetes (in female participants). However, since HNF4A and KLF14 are established loci for type 2 diabetes, it is unlikely that HDL-C solely mediates these associations. PMID- 26670165 TI - Lack of improvement in survival rates for women under 50 with endometrial cancer, 2000-2011. AB - PURPOSE: To assess how first course of treatment affects cancer-specific survival in women diagnosed with endometrial cancer younger than 50 years old. METHODS: Public-use data from the Surveillance, Epidemiology, and End Results program were used. The study included 82,721 women diagnosed with primary, invasive endometrial cancer between 2000 and 2011. We assessed type of treatment using Cox's proportional hazards models to determine survival disparity by age and stage. RESULTS: Cancer-specific survival significantly improved for those aged >=50 years with late stage, but did not improve for those <50. First course of treatment significantly affected cancer-specific survival for endometrial cancer patients. Regardless of age, survival was greatly improved for late-stage patients who received a combination of surgery and radiation [hazard ratio (HR) 0.62 [95 % confidence interval (CI) 0.47-0.78] and 0.64 (95 % CI 0.59-0.68)] compared to those who received total hysterectomy with removal of ovaries and tubes. However, the proportion of patients who received combination therapy decreased over time. The magnitude of decrease was larger in patients <50 than in those aged >=50. Overall, about 24-57 % of the difference in cancer-specific survival over time in patients aged <50 was explained by their initial treatment. CONCLUSIONS: Improvement in cancer-specific survival was only seen in older women with late-stage diagnosis. Despite improvements in diagnoses and treatments, the difference in age-specific survival indicates that more should be done to understand why these rates are not improving for those younger than 50 years old. PMID- 26670166 TI - The Second Insubria Autumn School on Neuroimmune Pharmacology: Repurposing Established Drugs for Novel Indications. AB - The Second Insubria Autumn School on Neuroimmune Pharmacology was held at the University of Insubria in Varese (Italy) in November 16th-20th 2015, under the auspices of the Society on NeuroImmune Pharmacology, the Italian Society of Pharmacology, and the Italian Association for Neuroimmunology. The School was dedicated to the repurposing of established drugs for novel indications, considering the enormous opportunities for drug repositioning provided by the prominent innovative and interdisciplinary approaches peculiar to neuroimmune pharmacology. More than 40 graduate students and postdoctoral fellows from 12 european universities, research institutes and hospitals attended the School, and lectures were given by 20 internationally acknowledged experts in the fields of basic and clinical neurosciences, immunology, and pharmacology. A poster session provided young researchers the opportunity to present their results, and the best poster was given the Journal of Neuroimmune Pharmacology Young Investigator Award. PMID- 26670167 TI - Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment. AB - Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin users. PMID- 26670168 TI - A mixed choroid plexus papilloma and ependymoma. AB - We report a novel case of a mixed choroid plexus papilloma (CPP) and ependymoma with cartilaginous differentiation. This kind of mixed tumor has not been previously reported in the English literature. The patient was a 5-year-old girl, who presented with a 1-week history of fever and numbness of the right lower limb. Magnetic resonance imaging of the brain with gadolinium revealed a heterogeneously enhancing mass in the occipital horn of the left lateral ventricle. Histologically, the tumor showed an intermixed CPP area and a low grade papillary ependymoma-like area, which was studded with cartilage islands and psammoma bodies. In many foci, direct transition of CPP and ependymoma was observed, but there were no high-grade features. We report this novel case, describe the unique microscopic and immunohistochemical features, and speculate on the pathogenesis. PMID- 26670169 TI - Pilomyxoid astrocytomas with rare rosenthal fibers. AB - Pilomyxoid astrocytomas (PMAs) were first officially described in 2007. Since then, intermediate pilomyxoid tumors with histopathological features typical of both PMAs and pilocytic astrocytomas (PAs) have been described. However, we found evidence of tumors that are histologically like PMAs but contain rare Rosenthal fibers, which have been reported in PAs but not in PMAs. We retrospectively analyzed four such cases involving a 16-year-old adolescent with a 3-cm recurring suprasellar tumor, an 11-year-old boy with a nonrecurring 3-cm mass in the left cerebellum, an 18-year-old adolescent with a mass in the suprasellar cistern who died 2 days after total tumor resection, and a 26-year-old woman with a nonrecurring 2-cm mass in the right temporal lobe. Microscopically, the tumors were a monomorphous population of small bipolar cells in a prominent myxoid/mucoid background with rare Rosenthal fibers. The tumor cells infiltrated the adjacent brain parenchyma. Findings for glial fibrillary acidic protein and oligodendrocyte transcription factor were positive, and the Ki-67 protein proliferation index was about 2%. Our findings document the existence of tumors that are histologically like PMAs but also have Rosenthal fibers. Studies of more such cases are needed for clarification of such tumors' clinical features. PMID- 26670170 TI - Impact of routine manual aspiration thrombectomy on outcomes of patients undergoing primary percutaneous coronary intervention for acute myocardial infarction: A meta-analysis. AB - BACKGROUND: The efficacy and safety of thrombectomy as an adjunct to primary percutaneous intervention (PCI) in the management of acute myocardial infarction (AMI) are debated. We performed a meta-analysis of randomized trials comparing primary PCI performed with versus without routine aspiration thrombectomy (AT). METHODS: A meta-analysis of randomized AT trials reporting clinical outcomes was done in accordance with the PRISMA guidelines. Trials reporting only non-clinical endpoints and those of technologies other than manual devices were excluded. The primary endpoint of this meta-analysis was mortality (either all-cause or cardiovascular). Secondary endpoints were reinfarction, stent thrombosis, and stroke. RESULTS: Seventeen randomized trials, involving 20,853 patients were included. Weighted mean follow-up was 9.3 +/- 3.3 months. The rates of all-cause mortality (reported in 14 trials, n = 10,430) and cardiovascular mortality (reported in 6 trials, n = 11,810) did not differ significantly between patients treated with or without AT (4.6% vs. 5.3%, RR = 0.88 [95%CI = 0.75-1.04]; and, 3.0% vs. 3.7%, RR = 0.83 [95%CI = 0.68-1.01]; respectively). The rates of reinfarction and stent thrombosis were also similar in patients treated with versus those treated without AT (2.1% vs. 2.2%; RR = 0.96 [95%CI = 0.80-1.15]; and, 1.2% vs. 1.4%; RR = 0.84 [95%CI = 0.65-1.07], respectively). However, stroke rates were increased with AT (0.84% vs. 0.52%, RR = 1.56 [95%CI = 1.09-2.25]). CONCLUSIONS: Routine AT as an adjunct to primary PCI does not reduce the rates of death, reinfarction, or stent thrombosis, but is associated with increased stroke risk. PMID- 26670171 TI - Percutaneous left atrial appendage occlusion: Device thrombosis in clopidogrel non-responders. PMID- 26670172 TI - Heart failure with preserved ejection fraction: A clinical crisis. AB - A previously less known form of heart failure (Heart Failure with Preserved Ejection Fraction, HFPEF) is on the rise. This article discusses the threat this poses and what could be done including a call for dedicated HFPEF clinics run jointly by cardiologists and geriatricians. PMID- 26670173 TI - Usefulness of the SAME-TT2R2 score to predict anticoagulation control on VKA in patients with atrial fibrillation and obstructive sleep apnea. AB - BACKGROUND: Oral anticoagulation is crucial for the prevention of stroke and thromboembolism in atrial fibrillation (AF). One of the comorbidities potentially affecting thromboembolic risk and anticoagulation effectiveness is obstructive sleep apnea (OSA). The objective of this study was to establish if presence of OSA is associated with poor expected benefit from vitamin K antagonist (VKA) therapy as assessed using the SAMe-TT2R2 score. METHODS: We studied AF patients planned for invasive electrophysiological procedures. All patients had a whole night polygraphy performed for the diagnosis of OSA, and their SAMe-TT2R2 score was calculated. RESULTS: We studied 211 AF patients (mean age = 57.1 +/- 10.2 years, 62.6% males). OSA with apnea-hypopnea index (AHI) >= 15/h was found in 48 (22.7%) patients. Mean SAMe-TT2R2 score in non-OSA patients was 1.4 +/- 0.9, compared to mild OSA patients, 1.5 +/- 0.9; moderate OSA patients, 1.9 +/- 1.1; and severe OSA patients, 2.8 +/- 0.6. A significantly higher percentage of patients with SAMe-TT2R2 >= 2, indicating poor predicted INR control on VKAs, was found with increasing AHI category (37% vs. 41% vs. 57% vs. 100%, respectively). Patients with poor predicted anticoagulation control (SAMe-TT2R2 >= 2) had a higher prevalence of OSA. There was a lower proportion of patients with TTR > 70% among patients with moderate/severe OSA compared to no/mild OSA (13.6% vs. 29.6%, p = 0.03). CONCLUSION: SAMe-TT2R2 scores in patients with OSA are substantially higher than in those without sleep-disordered breathing. The mean SAMe-TT2R2 score, as well as the percentage of patients with SAMe-TT2R2 score >= 2, suggests poor predicted anticoagulation control on VKA rises along with the AHI. There was a lower proportion of patients with TTR > 70% among patients with moderate/severe OSA, compared to no/mild OSA. PMID- 26670174 TI - The impact of left ventricular ejection fraction on fractional flow reserve: Insights from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial. AB - BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial. METHODS: From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both <= 40%, n = 90 and <= 50%, n = 252) and preserved EF (> 40%, n = 825 and > 50%, n = 663) according to the angiographic stenosis severity. We also compared differences in 1 year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF. RESULTS: Both groups had similar FFR values in lesions with 50-70% stenosis (p = 0.49) and with 71-90% stenosis (p = 0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p = 0.02), although the vast majority of FFR values remained <= 0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk = 0.76, p = 0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk = 0.81, p = 0.25). The results were similar with an EF cutoff of 40%. CONCLUSION: Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF. PMID- 26670175 TI - [Non-infectious granulomatous inflammation: Focus on the lungs and skin]. AB - Whereas a granulomatous reaction represents a physiologically useful immune defense mechanism against many infections, in autoimmune diseases granuloma formation and the concomitant inflammatory mechanisms may provoke a potentially organ-threatening reaction. Morphologically, several defined sub-types of granuloma have long been known, e.g. foreign body granuloma, tuberculous granuloma,sarcoid, pseudosarcoid, rheumatoid and rheumatic fever granulomas. However, in practice, assigning granulomas to a certain etiology from a biopsy or resection specimen can be a challenging diagnostic process. This article gives a practically oriented overview of the clinically most relevant non-infectious granulomatous diseases. The etiology, epidemiology, clinical correlation and morphology of granulomatous diseases are discussed, focussing on the lungs and skin. PMID- 26670176 TI - Mechanically Stiff Nanocomposite Hydrogels at Ultralow Nanoparticle Content. AB - Although hydrogels are able to mimic native tissue microenvironments, their utility for biomedical applications is severely hampered due to limited mechanical stiffness and low toughness. Despite recent progress in designing stiff and tough hydrogels, it is still challenging to achieve a cell-friendly, high modulus construct. Here, we report a highly efficient method to reinforce collagen-based hydrogels using extremely low concentrations of a nanoparticulate reinforcing agent that acts as a cross-link epicenter. Extraordinarily, the addition of these nanoparticles at a 10 000-fold lower concentration relative to polymer resulted in a more than 10-fold increase in mechanical stiffness and a 20 fold increase in toughness. We attribute the high stiffness of the nanocomposite network to the chemical functionality of the nanoparticles, which enabled the cross-linking of multiple polymeric chains to the nanoparticle surface. The mechanical stiffness of the nanoengineered hydrogel can be tailored between 0.2 and 200 kPa simply by manipulating the size of the nanoparticles (4, 8, and 12 nm), as well as the concentrations of the nanoparticles and polymer. Moreover, cells can be easily encapsulated within the nanoparticulate-reinforced hydrogel network, showing high viability. In addition, encapsulated cells were able to sense and respond to matrix stiffness. Overall, these results demonstrate a facile approach to modulate the mechanical stiffness of collagen-based hydrogels and may have broad utility for various biomedical applications, including use as tissue-engineered scaffolds and cell/protein delivery vehicles. PMID- 26670177 TI - Novel diether compounds inhibiting differentiation of osteoclasts. AB - Osteoporosis is a disorder in which bone mass decreases and is responsible for many degenerative bone diseases. The excessive formation and activity of osteoclasts results in pathological disorders of the bone. Receptor Activator of Nuclear Factor kappaB Ligand (RANKL) is regarded as a key regulator of osteoclast activity and as a new therapeutic target for treating osteoporosis. Herein, we have synthesized several new small molecules and tested their inhibition activity on RANKL-induced osteoclast formation. The active compounds 2c and 4d showed inhibitory activity against RANKL-induced osteoclast differentiation (IC50 = 1.56 and 2.20 MUM, respectively). The most active compound 2c prevented LPS-induced osteoclastogenesis in vivo. These data imply that the compound may be the potential candidate for a new therapeutic drug for treatment of bone resorption associated diseases. PMID- 26670178 TI - Optimization of Astaxanthin microencapsulation in hydrophilic carriers using response surface methodology. AB - Astaxanthin (3, 3'-dihydroxy-beta, beta-carotene-4, 4'-dione; AST) belongs to class of xanthophylls and is very effective antioxidant. It has very poor aqueous solubility resulting in lower bioavailability which presents major concerns in product development for oral use. AST was microencapsulated with soluble polymers using spray drying to improve its solubility and bioavailability. Quality by Design (QbD), a widely used approach for prediction of quality for desired specifications and effects was applied Design of Experiments (DOE), a useful component of QbD was utilized to understand the effect of variables and their interactions. Different formulation variables like ratio of hydrophilic carriers, concentration of solubilizers and homogenizer speed were challenged in the experimental design during the process of microencapsulation. The optimized formulation showed consistent release rate and characterization was done by DSC, XRD and SEM study. Percent cell growth inhibition was increased in optimized formulation as compared to plain AST. This QbD study can form a basis for further development of poorly water soluble AST formulation by oral route with improved bioavailability on larger scale. PMID- 26670179 TI - Register-Based Evaluation of Relative Effectiveness of New Therapies: Biologics Versus Conventional Agents in Treatment of Psoriasis in Sweden. AB - BACKGROUND: The Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) was established in 2006. This article analyzes the implementation phase of biologics in the treatment of moderate to severe psoriasis in Sweden in the period 2006-2012. Clinical studies have shown efficacy of biologic agents in psoriasis, but their relative effectiveness in real-world clinical practice has rarely been studied. OBJECTIVE: To estimate the incremental changes in clinical health-related quality-of-life measures in patients receiving biologics versus conventional systemic agents. METHODS: Patients fulfilling the clinical criteria for moderate to severe psoriasis were included. Average treatment effects were estimated from longitudinal data as incremental changes in: (1) the Psoriasis Area and Severity Index (PASI) score, (2) the Dermatology Life Quality Index (DLQI) score, and (3) the EQ-5D score, by matching patients switching to biologics with patients remaining on conventional systemic agents. RESULTS: The study included 239 biologic-treated patients and 378 conventionally treated patients. The matched patient groups were essentially equivalent in terms of important patient characteristics. The average treatment effects of biologics versus conventional systemic agents were 2.2 for PASI, 3.5 for DLQI, and 0.11 for EQ-5D. The estimated incremental benefits of biologics for the subgroup of patients not responding to their conventional systemic agent were even greater. CONCLUSION: Register-based research complements knowledge from randomized controlled trials regarding relative effectiveness in clinical practice. This information can be used to support health care decision making. This research suggests that there is both under- and overtreatment with biologics in Swedish clinical practice. Reallocation of biologics to more severe cases of psoriasis could improve overall health in the total patient population. PMID- 26670180 TI - The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis. AB - Experimental studies indicate that sepsis causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative damage, and inflammation on lung injury, following sepsis model by cecal ligation and puncture, and the effects of quercetin, antioxidant, and anti inflammatory flavonoid, in the lung tissue were investigated. In the present study, we found that administration of single-dose quercetin before cecal ligation and puncture procedure, while markedly diminishing the levels of YKL-40 and oxidant molecules (xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA)), increases the antioxidant enzymes levels. Quercetin is beneficial to acute lung injury by decreasing the levels of oxidative stress markers and increasing the antioxidant enzyme activities. Quercetin also causes a decrease in the serum levels of YKL-40 and periostin in the oxidative lung injury induced by the experimental sepsis model. PMID- 26670181 TI - Reinstatement of an extinguished fear conditioned response in infant rats. AB - Although it is currently accepted that the extinction effect reflects new context dependent learning, this is not so clear during infancy, because some studies did not find recovery of the extinguished conditioned response (CR) in rodents during this ontogenetic stage. However, recent studies have shown the return of an extinguished CR in infant rats. The present study analyzes the possibility of recovering an extinguished CR with a reinstatement procedure in a fear conditioning paradigm, on PD17 (Experiments 1-4) and on PD24 (Experiment 5), while exploring the role of the olfactory content of the context upon the reinstatement effect during the preweanling period. Preweanling rats expressed a previously extinguished CR after a single experience with an unsignaled US. Furthermore, this result was only found when subjects were trained and tested in contexts that included an explicit odor, but not in standard experimental cages. Finally, Experiment 5 demonstrated the reinstatement effect on PD24 in a standard context. These results support the notion that extinction during infancy has the same characteristics as those described for extinction that occurs in adulthood. Instead of postulating a different mechanism for extinction during infancy, we propose that it may be more accurate to view the problem in terms of the variables that may differentially modulate the extinction effect according to the stages of ontogeny. PMID- 26670182 TI - Synapsin is required to "boost" memory strength for highly salient events. AB - Synapsin is an evolutionarily conserved presynaptic phosphoprotein. It is encoded by only one gene in the Drosophila genome and is expressed throughout the nervous system. It regulates the balance between reserve and releasable vesicles, is required to maintain transmission upon heavy demand, and is essential for proper memory function at the behavioral level. Task-relevant sensorimotor functions, however, remain intact in the absence of Synapsin. Using an odor-sugar reward associative learning paradigm in larval Drosophila, we show that memory scores in mutants lacking Synapsin (syn(97)) are lower than in wild-type animals only when more salient, higher concentrations of odor or of the sugar reward are used. Furthermore, we show that Synapsin is selectively required for larval short-term memory. Thus, without Synapsin Drosophila larvae can learn and remember, but Synapsin is required to form memories that match in strength to event salience-in particular to a high saliency of odors, of rewards, or the salient recency of an event. We further show that the residual memory scores upon a lack of Synapsin are not further decreased by an additional lack of the Sap47 protein. In combination with mass spectrometry data showing an up-regulated phosphorylation of Synapsin in the larval nervous system upon a lack of Sap47, this is suggestive of a functional interdependence of Synapsin and Sap47. PMID- 26670184 TI - Possible overlapping time frames of acquisition and consolidation phases in object memory processes: a pharmacological approach. AB - In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when administered within 2 min after the acquisition trial. Likewise, both PDE5-I and PDE4-I reversed the scopolamine deficit model when administered within 2 min after the learning trial. PDE5-I was effective up to 45 min after the acquisition trial and PDE4-I was effective when administered between 3 and 5.5 h after the acquisition trial. Taken together, our study suggests that acetylcholine, cGMP, and cAMP are all involved in acquisition processes and that cGMP and cAMP are also involved in early and late consolidation processes, respectively. Most important, these pharmacological studies suggest that acquisition processes continue for some time after the learning trial where they share a short common time frame with early consolidation processes. Additional brain concentration measurements of the drugs suggest that these acquisition processes can continue up to 4-6 min after learning. PMID- 26670185 TI - Who, when, and where? Age-related differences on a new memory test. AB - Our study examined age-related differences on a new memory test assessing memory for "who," "when," and "where," and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct face-place pairs in the correct sequence compared with young adults. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity. Our results offer insight into age-related changes in the ability to remember associations between people and places at different points in time using a portable test that can be administered rapidly in various settings. PMID- 26670183 TI - Spermidine-induced improvement of reconsolidation of memory involves calcium dependent protein kinase in rats. AB - In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus. Twenty-four hours after training, animals were re-exposed to the apparatus in the absence of shock (reactivation session). Immediately after the reactivation session, spermidine (2-200 pmol/site), the PKC inhibitor 3 [1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl) maleimide hydrochloride (GF 109203X, 0.3-30 pg/site), the antagonist of the polyamine-binding site at the NMDA receptor, arcaine (0.2-200 pmol/site), or the PKC activator phorbol 12 myristate 13-acetate (PMA, 0.02-2 nmol/site) was injected. While the post reactivation administration of spermidine (20 and 200 pmol/site) and PMA (2 nmol/site) improved memory reconsolidation, GF 109203X (1, 10, and 30 pg/site) and arcaine (200 pmol/site) impaired it. GF 109203X (0.3 pg/site) impaired memory reconsolidation in the presence of spermidine (200 pmol/site). PMA (0.2 nmol/site) prevented the arcaine (200 pmol/site)-induced impairment of memory reconsolidation. Anisomycin (2 ug/site) also impaired memory reconsolidation in the presence of spermidine (200 pmol/site). Drugs had no effect when they were administered in the absence of reactivation. These results suggest that the spermidine-induced enhancement of memory reconsolidation involves PKC activation. PMID- 26670186 TI - Individual differences in the expression of conditioned fear are associated with endogenous fibroblast growth factor 2. AB - These experiments examined the relationship between the neurotrophic factor fibroblast growth factor 2 (FGF2) and individual differences in the expression of conditioned fear. Experiments 1 and 2 demonstrated that rats naturally expressing low levels of contextual or cued fear have higher levels of hippocampal FGF2 relative to rats that express high levels of conditioned fear and nonconditioned rats. Experiment 3 demonstrated that hippocampal FGF2 is not increased in rats that exhibit pharmacological-induced amnesia of conditioned fear. Together, these experiments provide evidence that FGF2 may be an endogenous regulator of fear responses to conditioned stimuli. PMID- 26670187 TI - Effects of post-encoding stress on performance in the DRM false memory paradigm. AB - Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false memory task) and memory was tested 24 h later. Stress decreased recognition of studied words, while increasing false recognition of semantically related lure words. Moreover, while control subjects remembered true and false words equivalently, stressed subjects remembered more false than true words. These results suggest that stress supports gist memory formation in the DRM task, perhaps by hindering detail-specific processing in the hippocampus. PMID- 26670188 TI - A Modified Approach to Inducing Bone Marrow Stromal Cells to Differentiate into Cells with Mature Schwann Cell Phenotypes. AB - Marrow stromal cells (MSCs) can be induced to differentiate into Schwann-like cells under classical induction conditions. However, cells derived from this method are unstable, exhibiting a low neurotrophin expression level after the induction conditions are removed. In Schwann cell (SC) culture, progesterone (PROG) enhances neurotrophic synthesis and myelination, specifically regulating the expression of the myelin protein zero (P0)- and peripheral myelin protein 22 (PMP22)-encoding genes by acting in concert or in synergy with insulin and glucocorticoids (GLUCs). In the present study, we investigated whether combined PROG, GLUC, and insulin therapy induced MSCs to differentiate into modified SC like cells with phenotypes similar to those of mature SCs. After being cultured for 2 weeks in modified differentiation medium, the modified SC-like cells showed increased expression of P0 and PMP22. In addition, morphological and phenotypic characterizations were conducted over a period of over 2 weeks, and functional characteristics persisted for more than 3 weeks after the induction reagents were withdrawn. The transplantation of green fluorescent protein-labeled, modified SC like cells into transected sciatic nerves with a 10-mm gap significantly increased the proliferation of the original SCs and improved axon regeneration and myelination compared with original BM-SCs. Immunostaining for P0 revealed that more of the transplanted modified SC-like cells retained the phenotypic characteristics of SCs. Taken together, these results reveal that the combined application of PROG, GLUC, and insulin induces MSCs to differentiate into cells with phenotypic, molecular, and functional properties of mature SCs. PMID- 26670190 TI - The safety, efficacy, and durability of lung-volume reduction surgery: A 10-year experience. AB - OBJECTIVES: The National Emphysema Treatment Trial (NETT) validated the efficacy of lung-volume reduction surgery (LVRS) in selected patients with emphysema; however, concerns about the safety and durability of the operation have limited its clinical application. We evaluated our experience with LVRS, for the time period since approval was given by the Centers for Medicare and Medicaid Services, with respect to surgical morbidity and mortality, early and late functional outcomes, and long-term survival. METHODS: Retrospective analysis was performed on 91 patients for whom consent was obtained for bilateral LVRS at our institution between January 2004 and June 2014. Primary outcomes analyzed were 6 month surgical mortality and overall survival at 1, 2, and 5 years. Secondary outcomes (forced expiratory volume in 1 second [FEV1], residual volume, carbon monoxide diffusing capacity, a 6-minute walk test, exercise capacity, and a shortness-of-breath questionnaire) were analyzed for mean change from baseline at 1, 2, and 5 years after LVRS. RESULTS: The 6-month surgical mortality rate was 0%. At the 1- and 5-year follow-up, 69% and 36% of the patients had an improvement in FEV1. The 1-, 2-, and 5-year FEV1 change in % predicted of the FEV1, compared with baseline after LVRS, respectively, was 11.1% (95% CI: 8.6%, 13.6%); 8.7% (95% CI: 6.1%, 11.4%); and 11.1% (95% CI: 7.1%, 15.0%); and the maximal workload (in watts [W]) had an average increase of: 10.7 W (95% CI: 6.9, 14.6); 7.6 W (95% CI: 2.8, 12.4); and 10.24 W (95% CI: 4.4, 16.1). Overall survival (95% CI) for the group was: 0.99 (95% CI: 0.96, 1.00) at 1 year; 0.97 (95% CI: 0.93, 1.00) at 2 years; and 0.78 (95% CI: 0.67, 0.89) at 5 years. CONCLUSIONS: Given proper patient selection, LVRS is a safe operation. Early functional measurements are consistent with significant clinical benefit. Long term results demonstrate that improvements can be durable. Surgical LVRS continues to represent the standard for lung-volume reduction therapy. PMID- 26670189 TI - Reproductive Regulation of Gene Expression in the Hypothalamic Supraoptic and Paraventricular Nuclei. AB - Oxytocin secretion is required for successful reproduction. Oxytocin is synthesised by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei and the physiological demand for oxytocin synthesis and secretion is increased for birth and lactation. Therefore, we used a polymerase chain reaction (PCR) array screen to determine whether genes that might be important for synthesis and/or secretion of oxytocin are up- or down-regulated in the supraoptic and paraventricular nuclei of late-pregnant and lactating rats, compared to virgin rats. We then validated the genes that were most highly regulated using real time-quantitative PCR. Among the most highly regulated genes were those that encode for suppressors of cytokine signalling, which are intracellular inhibitors of prolactin signalling. Prolactin receptor activation changes gene expression via phosphorylation of signal transducer and activator of transcription 5 (STAT5). Using double-label immunohistochemistry, we found that phosphorylated STAT5 was expressed in almost all oxytocin neurones of late pregnant and lactating rats but was almost absent from oxytocin neurones of virgin rats. We conclude that increased prolactin activation of oxytocin neurones might contribute to the changes in gene expression by oxytocin neurones required for normal birth and lactation. PMID- 26670192 TI - Discussion. PMID- 26670191 TI - Risk factors for development of endocarditis and reintervention in patients undergoing right ventricle to pulmonary artery valved conduit placement. AB - OBJECTIVE: To determine the incidence and risk factors for endocarditis and reintervention in patients undergoing placement of right ventricle-to-pulmonary artery valve conduits. METHODS: All right ventricle-to-pulmonary artery valved conduits placed between 1995 and 2014 were included. Freedom from endocarditis, reintervention, and replacement were analyzed using the Kaplan-Meier method and parametric survival regression models. RESULTS: A total of 586 patients underwent placement of a total of 792 valved conduits, including 289 (36%) pulmonary homografts, 121 (15%) aortic homografts, 245 (31%) bovine jugular grafts, and 137 (17%) porcine heterografts. There were 474 (60%) primary placements and 318 (40%) replacements. The median duration of conduit follow-up was 7 years; 23 conduits developed endocarditis at a median of 5 years after surgery. The use of bovine jugular grafts was the sole significant risk factor associated with endocarditis (hazard ratio, 9.05; 95% confidence interval, 2.6-31.8 compared with homografts). The hazard was greater for bovine jugular grafts compared with the other conduit types and increased with time; however, bovine jugular grafts were associated with a lower risk for reintervention (P < .0001) and replacement (P = .0002). Factors associated with greater risk of both reintervention and replacement were younger age and smaller conduit size. In addition, a diagnosis of truncus arteriosus was associated with a greater risk for replacement (P = .03). CONCLUSIONS: Bovine jugular grafts are associated with a significantly greater risk of late endocarditis but with lower reintervention rates compared with other valved conduits. The risk of endocarditis and durability must be balanced during conduit selection. Antibiotic prophylaxis and a high index of suspicion for endocarditis are warranted in patients with bovine jugular grafts. PMID- 26670193 TI - Freeze the pain away: The role of cryoanalgesia during a Nuss procedure. PMID- 26670194 TI - Discussion. PMID- 26670197 TI - Corrigendum. PMID- 26670196 TI - Hydrophobic Tagged Dihydrofolate Reductase for Creating Misfolded Glycoprotein Mimetics. AB - In the endoplasmic reticulum (ER), nascent glycoproteins that have not acquired the native conformation are either repaired or sorted for degradation by specific quality-control systems composed by various proteins. Among them, UDP glucose:glycoprotein glucosyltransferase (UGGT) serves as a folding sensor in the ER. However, the molecular mechanism of its recognition remains obscure. This study used pseudo-misfolded glycoproteins, comprising a modified dihydrofolate reductase with artificial pyrene-cysteine moiety on the protein surface (pDHFR) and Man9 GlcNAc2 -methotrexate (M9-MTX). All five M9-MTX/pDHFR complexes, with a pyrene group at different positions, were found to be good substrates of UGGT, irrespective of the site of pyrene modification. These results suggest UGGT's mode of substrate recognition is fuzzy, thus allowing various glycoproteins to be accommodated in the folding cycle. PMID- 26670195 TI - Small-molecule inhibitors of Wnt signaling pathway: towards novel anticancer therapeutics. AB - BACKGROUND: The Wnt signaling pathway involves secreted glycoproteins that bind to the Frizzled family receptors to activate intracellular signal transduction events that regulate cell proliferation, apoptosis, cell migration and many critical aspects of developmental biology. DISCUSSION: Aberrant Wnt signaling underlies a wide range of pathologies in humans including tumor initiation, tumor growth, cell senescence, cell death, differentiation and metastasis. The inhibition of Wnt signaling offers a novel approach for anticancer therapeutics. CONCLUSION: Focusing on recent developments, we reviewed the small-molecule inhibitors targeting various components of Wnt signaling pathways and the progress from the discovery of lead compounds to highly potent inhibitors with significant therapeutic potential. PMID- 26670198 TI - Predictive factors of pathological vascular invasion in hepatocellular carcinoma within 3 cm and three nodules without radiological vascular invasion. AB - AIM: The aim of this study was to determine the predictive factors of pathological vascular invasion as contra-indicators for ablation therapy in patients with hepatocellular carcinoma (HCC) within 3 cm and three nodules without radiological vascular invasion. METHODS: Two hundred and seventeen patients with HCC within 3 cm and three nodules without radiological vascular invasion who underwent hepatic resection were retrospectively investigated. RESULTS: Pathological vascular invasion was positive in 46 patients, consisting of 38 portal vein invasions, three hepatic vein invasions, two hepatic artery invasions, one hepatic duct invasion and two with portal and hepatic vein invasions. In univariate analysis, patients with alpha-fetoprotein (AFP) of more than 100 ng/mL had higher rates of pathological vascular invasion than those without. In addition, patients with protein induced by vitamin K absence (PIVKA II) of more than 100 mAU/mL had higher rates of pathological vascular invasion than those without. Multivariate analysis revealed that AFP of more than 100 ng/mL and PIVKA-II of more than 100 mAU/mL were independent predictive factors for pathological vascular invasion. As these patients were treated with hepatic resection, cumulative 5-year recurrence-free and overall survivals were not significantly different between the pathological vascular invasion negative and positive cases. CONCLUSION: AFP of more than 100 ng/mL and PIVKA-II of more than 100 mAU/mL can predict pathological vascular invasion in patients with HCC within 3 cm and three nodules without radiological vascular invasion. In treating such cases, hepatic resection rather than local ablation therapy is recommended. PMID- 26670199 TI - Extended nitric oxide analysis may improve personalized anti-inflammatory treatment in asthmatic children with intermediate F(E)NO50. AB - Exhaled nitric oxide (F(E)NO) is elevated in asthma, and a clinical practice guideline has been published with recommendations for anti-inflammatory treatment. It summarizes that a F(E)NO at an expiratory flow rate of 50 ml s(-1) (F(E)NO50) above 35 ppb in children indicates eosinophilic inflammation, and the most likely response is to use inhaled corticosteroids. Intermediate F(E)NO50 between 20-35 ppb should be interpreted cautiously. The aim of the study was to investigate this guideline in a small group of asthmatic children. Thirty-seven asthmatic children; 23 boys and 14 girls, visited the outpatient clinic, and provided exhaled breath samples for offline NO measurement. These samples were analysed with chemiluminescence techniques. Three flow rates, namely 16, 90 and 230 ml s(-1) were used for the extended NO analysis (Hogman-Merilainen algorithm, HMA) to estimate the alveolar concentration (C(A)NO), diffusion rate of the airway wall (D(aw)NO) and airway wall content (C(aw)NO). For accuracy of the HMA, the estimated value of F(E)NO at 50 ml s(-1) (F(E)NO50) was compared with measured F(E)NO50. In nine children the difference was more than 5 ppb and the data were therefore excluded. Five children with F(E)NO50 <20 ppb had no known allergy and their F(E)NO50 geometrical mean (25th; 75th percentile) was 11 (10;14) and CawNO was 32 (20;43) ppb. Ten children with F(E)NO50 > 35 ppb had an allergy and had F(E)NO50 of 56 (47;60) ppb and C(aw)NO of 140 (121;172) ppb. Thirteen children with allergies, with intermediate F(E)NO50, had F(E)NO50 of 27 (25;30) ppb with a wide range of C(aw)NO. In five of these children, values were comparable to healthy children, 44 (43;50) ppb while eight children had elevated C(aw)NO values of 108 (95;129) ppb. Our data indicate the clinical potential use of extended NO analysis to determine the personal target value of F(E)NO50 for monitoring the treatment outcome. Furthermore, for children with intermediate F(E)NO50 more than half of them could possibly benefit from an adjustment of inhaled corticosteroids if the C(aw)NO value was considered. PMID- 26670200 TI - Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era. AB - BACKGROUND: Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs. PATIENTS AND METHODS: Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression. RESULTS: In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P<0.02; HR = 1.4; 95% CI = 1.1 1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P<0.004). CONCLUSIONS: This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies. PMID- 26670201 TI - Orthotopic neobladder vs. ileal conduit urinary diversion: A long-term quality-of life comparison. AB - PURPOSE: The optimal form of urinary diversion following radical cystectomy remains controversial. We sought to compare the long-term health-related quality of-life outcomes between patients with orthotopic neobladder and ileal conduit diversion (ICD). PATIENTS AND METHODS: We enrolled 95 patients following radical cystectomy and ICD (n = 49) or orthotopic neobladder reconstruction (ONR) (n = 46), with a minimum interval of 1 year from surgery. All patients completed the Bladder Cancer Index questionnaire, assessing their urinary, bowel, and sexual function, and bother scores. RESULTS: Patients treated with ONR were generally younger and healthier compared with those who underwent ICD (P<0.01). Sex, marital status, disease status at the time of enrollment, and mean duration elapsing from surgery to interview were similar between the subgroups. Better functional scores in favor of ICD were recorded in the urinary domain (P<0.01), whereas the corresponding bother scores were roughly identical in both groups. Conversely, although higher functional scores were recorded in the sexual domain of patients with ONR (P<0.01), the corresponding bother scores in this group were lower compared with their counterparts with ICD (53.2 vs. 65.3; P<0.05). As patients grew older they were more likely to report on better urinary function and worse sexual function, but were less likely to be bothered by the decline in sexual function. CONCLUSIONS: Our study suggests that the bother resulting from urinary incontinence and the risk of sexual dysfunction be highlighted to those electing for neobladder reconstruction, whereas patients preferring conduit diversion should be reassured that their expected quality of life is not compromised. PMID- 26670202 TI - Characterization of clear cell renal cell carcinoma by gene expression profiling. AB - OBJECTIVES: Use global gene expression to characterize differences between high grade and low-grade clear cell renal cell carcinoma (ccRCC) compared with normal and benign renal tissue. METHODS: Tissue samples were collected from patients undergoing surgical resection for ccRCC. Affymetrix gene expression arrays were used to examine global gene expression patterns in high- (n = 16) and low-grade ccRCC (n = 13) as well as in samples from normal kidney (n =14) and benign kidney disease (n = 6). Differential gene expression was determined by analysis of variance with a false discovery rate of 1% and a 2-fold cutoff. RESULTS: Comparing high-grade ccRCC with each of normal and benign kidney resulted in 1,833 and 2,208 differentially expressed genes, respectively. Of these, 930 were differentially expressed in both comparisons. In order to identify genes most related to progression of ccRCC, these differentially expressed genes were filtered to identify genes that showed a pattern of expression with a magnitude of change greater in high-grade ccRCC in the comparison to low-grade ccRCC. This resulted in the identification of genes such as TMEM45A, ceruloplasmin, and E cadherin that were involved in cell processes of cell differentiation and response to hypoxia. Additionally changes in HIF1alpha and TNF signaling are highly represented by changes between high- and low-grade ccRCC. CONCLUSIONS: Gene expression differences between high-grade and low-grade ccRCC may prove to be valuable biomarkers for advanced ccRCC. In addition, altered signaling between grades of ccRCC may provide important insight into the biology driving the progression of ccRCC and potential targets for therapy. PMID- 26670203 TI - The relationship between hearing impairment and cognitive function: a meta analysis in adults. AB - OBJECTIVE: Hearing loss affects over 1.23 billion people globally. It has been proposed that hearing impairment negatively impacts on cognition. Some studies have demonstrated a faster rate of decline in cognition, and increased risk of incident all-cause dementia. This finding is not ubiquitous. This study used meta analysis to examine the evidence-base regarding the relationship between hearing and cognition. DESIGN: A systematic review of the literature and meta-analyses of study findings were conducted. Published and grey literature was reviewed. Papers were included if they studied the relationship between hearing and cognition in adults with and without hearing impairment. MAIN OUTCOME MEASURES: Meta-analyses examined evidence for and against seven questions. Is cognition poorer in individuals with normal hearing compared to (i) untreated or (ii) treated hearing impairment, is cognition associated with degree of hearing impairment in (iii) untreated and/or (iv) treated hearing, is cognition (v) different in untreated compared to treated hearing impairment, (vii) does cognition improve after intervention, and (vii) how is hearing impairment differentially associated with cognitive ability across six domains of cognition? RESULTS: The 33 included studies contributed 40 samples, with a total of 602 participants with untreated hearing impairment, 672 participants with treated hearing impairment, 176 healthy controls, and 4260 individuals with a range of hearing impairment with/without treatment. The results demonstrated that cognition is significantly poorer in (i) individuals with untreated hearing and remains poorer in (ii) treated hearing impairment compared to normal hearers. The degree of cognitive deficit is significantly associated with the degree of hearing impairment in both (iii) untreated and (iv) treated hearing impairment. Furthermore, (v) hearing intervention significantly improves cognition. Finally, (vii) hearing impairment impacted on all domains of cognition. CONCLUSIONS: This meta-analysis suggests that hearing impairment is associated with cognitive problems. However, due to diversity within studies, small sample sizes, the failure to control for premorbid and other health factors, this conclusion may be premature. PMID- 26670204 TI - A sucrose transporter-interacting protein disulphide isomerase affects redox homeostasis and links sucrose partitioning with abiotic stress tolerance. AB - Sucrose accumulation in leaves in response to various abiotic stresses suggests a specific role of this disaccharide for stress tolerance and adaptation. The high affinity transporter StSUT1 undergoes substrate-induced endocytosis presenting the question as to whether altered sucrose accumulation in leaves in response to stresses is also related to enhanced endocytosis or altered activity of the sucrose transporter. StSUT1 is known to interact with several stress-inducible proteins; here we investigated whether one of the interacting candidates, StPDI1, affects its subcellular localization in response to stress: StPDI1 expression is induced by ER-stress and salt. Both proteins, StSUT1 and StPDI1, were found in the detergent resistant membrane (DRM) fraction, and this might affect internalization. Knockdown of StPDI1 expression severely affects abiotic stress tolerance of transgenic potato plants. Analysis of these plants does not reveal modified subcellular localization or endocytosis of StSUT1, but rather a disturbed redox homeostasis, reduced detoxification of reactive oxygen species and effects on primary metabolism. Parallel observations with other StSUT1 interacting proteins are discussed. The redox status in leaves seems to be linked to the sugar status in response to various stress stimuli and to play a role in stress tolerance. PMID- 26670205 TI - Ectopic spleen and liver hemangioma mimicking metastatic pancreatic neuroendocrine tumor. AB - Pancreatic tumors comprise benign lesion and malignant lesion, most importantly pancreatic adenocarcinoma, acinar cell carcinoma, neuroendocrine carcinoma or metastasis. Surgical resection provides the only chance for cure for malignant pancreatic tumors. In some cases, surgical resection is performed because a malignant lesion is suspected, however, histopathological examinations eventually reveal a benign lesion. Here, we report the case of a 49-year-old woman, who was initially diagnosed with a neuroendocrine tumor of the pancreas with metastasis to the liver. The patient underwent distal pancreatectomy and atypical liver resection. Surprisingly, however, histopathological examination revealed an intrapancreatic accessory spleen (IPAS) of the pancreatic tail as well as liver hemangioma. This unique case report highlights the impact of extensive preoperative examinations to differentiate benign and malignant pancreatic lesions and, possibly, prevent patients from unnecessary surgery. PMID- 26670206 TI - CD200 increases alternatively activated macrophages through cAMP-response element binding protein - C/EBP-beta signaling. AB - The concept of macrophage polarization toward different phenotypes after CNS injury has been increasingly discussed. Here, we propose that CD200 treatment may help shift pro-inflammatory macrophages to an arginase 1 (Arg1)-, transglutaminase 2 (TGM2)-, and transforming growth factor beta 1 (TGF-beta) positive phenotype. Rat macrophages were stimulated by interferon gamma and lipopolysaccharide (LPS) to induce pro-inflammatory phenotypes. Treatment with human CD200-Fc up-regulated expression levels of alternatively activated M2-like markers such as Arg1 and TGM2 but suppressed pro-inflammatory M1-like markers such as toll-like receptor 4, interleukin 1 beta (IL-1beta), IL-6, and GM-CSF. Concomitantly, CD200-Fc enhanced (CCAAT/enhancer-binding protein) C/EBP-beta promoter activity, whereas NF-kappaB activity was suppressed. Treatment with CD200-Fc also up-regulated potentially beneficial TGF-beta expression in macrophages. When C/EBP-beta signaling was suppressed with siRNA, the effect of CD200-Fc on Arg1, TGM2 and TGF-beta up-regulation was canceled. Taken together, these data provide proof-of-principle that targeting CD200 signaling may be a novel therapeutic approach to shift macrophages toward M2-like polarization via modulating cAMP-response element binding protein-C/EBP-beta transcriptional activity. We showed that CD200 treatment decreased pro-inflammatory cytokines (IL 1beta, IL-6, and GM-CSF) along with suppressed inflammatory NF-kappaB activity in pro-inflammatory Mphi. On the other hand, CD200 increased Arg1, TGM2, and TGF beta production through CREB-C/EBPbeta signaling. We think that these findings provide proof-of-concept that CD200 signaling may play a key role in regulating macrophage polarization toward anti-inflammatory phenotypes. PMID- 26670207 TI - Intra-Cavitary Masses: Rare Presentation of a Common Illness in SAARC Nation. AB - Cardiovascular tuberculosis (TB) is a relatively uncommon manifestation of Mycobacterium tuberculosis infection. TB can affect all three layers of the heart; endocardial tuberculoma is the rarest form. Endocardial tuberculoma, when it occurs, can easily be confused with other common causes of intracardiac mass lesions, especially in echocardiography. Timely diagnosis and appropriate treatment is essential, as only this can lessen the associated morbidity and mortality. Here, a case of cardiovascular TB has been described in a middle-aged woman from the SAARC nation; the woman presented with simultaneous pericardial constriction and multichamber endocardial tuberculoma. Combined pharmacological and surgical approach was successful. PMID- 26670208 TI - Tele-intervention for children with hearing loss: A comparative pilot study. AB - Introduction This pilot study compared tele-intervention to conventional intervention for children with hearing loss in terms of communication performance, parental perceptions and clinician perceptions. Methods A within subject design was employed, including 10 children with hearing loss and their parents who each received a structurally similar tele-intervention and conventional intervention session in a counterbalanced manner. Quality of communication performance was analysed using a modified Tait video analysis method. Parent and clinician perceptions were collected through rating-scale surveys and thematic analysis of qualitative responses. Results No significant difference ( p > 0.05) was found between tele-intervention and conventional intervention in terms of communication performance of children. Parent perceptions were not significantly different ( p > 0.05) between conventional and tele-intervention in terms of facilitating meaningful communication interaction. Significant differences were evident for parents' comfort level during the session, whether they found it to be a beneficial experience and whether they would like to continue receiving intervention through this method. Clinician perceptions of conventional and tele-intervention were not significantly different ( p > 0.05) and tele-intervention was deemed a valuable method of service delivery for clients. Discussion This study provides preliminary evidence that tele-intervention is effective for communication intervention and can be a valuable solution to typical barriers such as distance and the shortage of trained interventionists. PMID- 26670209 TI - Home monitoring of heart failure patients at risk for hospital readmission using a novel under-the-mattress piezoelectric sensor: A preliminary single centre experience. AB - Introduction A piezoelectric sensor (PS) converts mechanical deformations into electrical signals. We used a contactless under-the-mattress PS to monitor physiological vibrations resulting from breathing, pumping of the heart, and body movements, among individuals at home following hospitalization for heart failure (HF). Our objectives were to assess acceptability of the device in the home, to assess physiological patterns, and to determine if altered patterns correlate with readmission. Methods We conducted a prospective observational study of 30 patients discharged home following HF hospitalization. PS data included a continuous nightly assessment of heart rate, respiration rate, movement rate, rapid and shallow respiration duration, and a behaviour score. We utilized random forest classification to classify average nightly data by readmission status. Results We collected 640 nights of PS data from 29 patients. There were nine readmissions, of which four were for HF. PS monitoring was tolerated by all but one of the participants. We inspected continuous nightly physiological profiles and noted differences between patients who were and were not readmitted. Patients readmitted for HF had higher average heart and respiration rates, and more respiration variability. Average nightly respiratory rate was most predictive of readmission. Discussion We are the first to study nocturnal physiological patterns of HF patients at home using a contactless under-the-mattress monitoring system. We noted patterns that may be unique to patients at risk for readmission due to HF. Respiratory rate was the most important risk-adjusted associate of readmission for HF. Further studies should investigate the efficacy of home PS monitoring in HF populations. PMID- 26670210 TI - Examining user perceptions of SwallowIT: A pilot study of a new telepractice application for delivering intensive swallowing therapy to head and neck cancer patients. AB - Consumer feedback and end-user perceptions provide important information regarding the clinical acceptability of new telepractice systems. This pilot investigation aimed to evaluate end-user perceptions of a new asynchronous telepractice application, ' SwallowIT', designed to support patients to remotely complete intensive swallowing therapy during curative chemoradiotherapy (CRT) treatment for head and neck cancer (HNC). Insights were sought from 15 patients with oropharyngeal cancer who used SwallowIT to complete supported home swallowing therapy. Perceptions were evaluated via structured questionnaires, completed following initial orientation to SwallowIT and on completion of CRT. Semi-structured phone interviews were conducted >=3 months post-treatment. The majority of patients reported positive initial perceptions towards SwallowIT for comfort (87%), confidence (87%), motivation (73%) and support (87%). No statistically significant change in perceptions was observed from baseline to end of CRT ( p > 0.05). Thematic analysis of interviews revealed four main themes: the ease of use of SwallowIT, motivating factors, circumstances which made therapy difficult, and personal preferences for service-delivery models. These preliminary findings demonstrate that SwallowIT was well-perceived by the current group of HNC consumers and suggest that SwallowIT may be well-accepted as an alternate service-delivery model for delivering intensive swallowing therapy during CRT. PMID- 26670213 TI - Multiallelic Positions in the Human Genome: Challenges for Genetic Analyses. AB - As the amount of human genomic sequence available from personal genomes and exomes has increased, so too has the observation of genomic positions having two or more alternative alleles, so-called multiallelic sites. For portions of the haploid genome that are present in more than one copy, including segmental duplications, variation at such multisite variant positions becomes even more complex. Despite the frequency of multiallelic variants, a number of commonly used resources and tools in genomic research and diagnostics do not support these multiallelic variants all together or require special modifications. Here, we explore the frequency of multiallelic sites in large samples with whole exome sequencing and discuss potential outcomes of failing to account for multiple variant alleles. We also briefly discuss some commonly utilized resources that fully support multiallelic sites. PMID- 26670215 TI - Possible correlations between annular pustular psoriasis and Noonan syndrome. PMID- 26670216 TI - 9th IWA symposium on waste management problems in agro-industries-AGRO'2014. PMID- 26670214 TI - CYP2A6 genotyping methods and strategies using real-time and end point PCR platforms. AB - CYP2A6 genotyping is of clinical importance--CYP2A6 gene variants influence nicotine metabolism and are associated with nicotine dependence, cigarettes per day, smoking cessation and the risk for tobacco-associated cancers. CYP2A6 gene variants also influence the metabolism of therapeutic drugs, such as the anticancer agents, tegafur and letrozole. Over the years, CYP2A6 genotyping methods have evolved to incorporate novel gene variants and to circumvent genotyping errors resulting from the high degree of homology between CYP2A6 and neighboring CYP2A genes. Herein, CYP2A6 genotyping strategies are described for commonly genotyped functionally significant alleles including SNPs, small insertions/deletions and more complex structural variants. The methods presented utilize higher throughput SYBR green real-time PCR technology in addition to standard thermocycling. PMID- 26670217 TI - Ecological factors influencing habitat use by chimpanzees at Ngogo, Kibale National Park, Uganda. AB - Although numerous ecological and social factors influence range use in vertebrates, the general assumption is that ranging patterns typically accord with principles of optimal foraging theory. However, given temporal variability in resource abundance, animals can more easily meet nutritional needs at some times than at others. For species in which sociality is particularly important for fitness, such as chimpanzees (Pan troglodytes) and other group-living primates, the influences of social factors can be particularly strong, and likely interact closely with ecological factors. We investigated home range use by a community of chimpanzees at Ngogo, Kibale National Park, Uganda, to determine whether range use corresponded to energy-based optimality principles. Chimpanzees were particularly attracted to areas of the home range where individuals of Ficus mucuso (a large but low-density resource) were found, but only if those areas also offered other preferred or important resource classes. The aggregation of large foraging parties at F. mucuso crowns (frequently seen year-round) facilitates a number of socially beneficial activities for both males and females. Because chimpanzees apparently seek out F. mucuso in areas where other high-quality feeding opportunities exist, these social benefits likely do not come at the expense of fitness benefits accrued from feeding on high-quality resources. Am. J. Primatol. 78:432-440, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26670218 TI - Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships. AB - BACKGROUND: Antiretroviral therapy (ART) markedly reduces the risk of HIV-1 transmission in serodiscordant partnerships. We previously found that younger age and higher CD4 counts were associated with delayed initiation of ART by HIV-1 infected partners in serodiscordant partnerships. Among those initiating ART, we sought to explore whether those same factors were associated with failure to achieve viral suppression. METHODS: In a prospective study of HIV-1-infected persons who had a known heterosexual HIV-1-uninfected partner in Kenya and Uganda [Partners Pre-Exposure Prophylaxis (PrEP) Study], we used Cox proportional hazards regression to evaluate correlates of viral nonsuppression (HIV-1 RNA >80 copies/ml). RESULTS: Of 1,035 HIV-1-infected participants initiating ART, 867 (84%) achieved viral suppression: 77% by 6 months and 86% by 12 months. Younger age [adjusted hazard ratio (aHR) 1.05 for every 5 years younger; p = .006], lower pretreatment CD4 count (aHR 1.26; p = .009 for <=250 compared with >250 cells/MUl), and higher pretreatment HIV-1 RNA quantity (aHR 1.21 per log10; p < .001) independently predicted failure to achieve viral suppression. Following initial viral suppression, 8.8% (76/867) experienced virologic rebound (HIV-1 RNA >200 copies/ml): 6.3% and 11.5% by 6 and 12 months after initial suppression, respectively. Age was the only factor associated with increased risk of virologic rebound (aHR 1.33 for every 5 years younger; p = .005). CONCLUSIONS: For HIV-1 infected persons in serodiscordant couples, younger age was associated with delayed ART initiation, failure to achieve viral suppression, and increased risk of virologic rebound. Motivating ART initiation and early adherence is a key to achieving and sustaining viral suppression. PMID- 26670219 TI - Genomic and Gene-Expression Comparisons among Phage-Resistant Type-IV Pilus Mutants of Pseudomonas syringae pathovar phaseolicola. AB - Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Phi6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Phi6 as a model system in evolutionary biology, Pph resistance to phage Phi6 remains poorly characterized. To investigate differences between phage Phi6 resistant Pph strains, we examined genomic and gene expression variation among three bacterial genotypes that differ in the number of type IV pili expressed per cell: ordinary (wild-type), non-piliated, and super-piliated. Genome sequencing of non-piliated and super-piliated Pph identified few mutations that separate these genotypes from wild type Pph--and none present in genes known to be directly involved in type IV pilus expression. Expression analysis revealed that 81.1% of gene ontology (GO) terms up-regulated in the non-piliated strain were down-regulated in the super-piliated strain. This differential expression is particularly prevalent in genes associated with respiration--specifically genes in the tricarboxylic acid cycle (TCA) cycle, aerobic respiration, and acetyl-CoA metabolism. The expression patterns of the TCA pathway appear to be generally up and down-regulated, in non-piliated and super-piliated Pph respectively. As pilus retraction is mediated by an ATP motor, loss of retraction ability might lead to a lower energy draw on the bacterial cell, leading to a different energy balance than wild type. The lower metabolic rate of the super-piliated strain is potentially a result of its loss of ability to retract. PMID- 26670221 TI - Design, Synthesis and Bioactivities of Novel Dichloro-Allyloxy-Phenol-Containing Pyrazole Oxime Derivatives. AB - In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by 1H-NMR, (13)C-NMR and elemental analysis. In addition, bioassays showed that all of the newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 MUg/mL, and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm even at the dose of 20 MUg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90% inhibition rates, respectively, which were comparable to that of the control pyridalyl. PMID- 26670222 TI - Nanocasting of Periodic Mesoporous Materials as an Effective Strategy to Prepare Mixed Phases of Titania. AB - Mesoporous titanium dioxide materials were prepared using a nanocasting technique involving silica SBA-15 as the hard-template. At an optimal loading of titanium precursor, the hexagonal periodic array of pores in SBA-15 was retained. The phases of titanium dioxide could be easily varied by the number of impregnation cycles and the nature of titanium alkoxide employed. Low number of impregnation cycles produced mixed phases of anatase and TiO2(B). The mesoporous TiO2 materials were tested for solar hydrogen production, and the material consisting of 98% anatase and 2% TiO2(B) exhibited the highest yield of hydrogen from the photocatalytic splitting of water. The periodicity of the pores was an important factor that influenced the photocatalytic activity. This study indicates that mixed phases of titania containing ordered array of pores can be prepared by using the nanocasting strategy. PMID- 26670220 TI - Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators. AB - BACKGROUND: Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts. AIMS & METHODS: In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real time PCR, western blotting and functional assays. FINDINGS: We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases. PMID- 26670223 TI - Exploring the Reactivity of Na[W2(MU-Cl)3Cl4(THF)2]?(THF)3 towards the Polymerization of Selected Cycloolefins. AB - The bimetallic compound Na[W2(MU-Cl)3Cl4(THF)2].(THF)3 (1, {W (3) W}(6+), a'2e'4) is a highly efficient room-temperature initiator for ring opening metathesis polymerization (ROMP) of norbornene (NBE) and some of its derivatives. In most cases, addition of phenylacetylene (PA) as co-initiator improves the catalytic activity and retains the high cis-stereoselectivity. On the other hand, 1 can polymerize cyclopentadiene (CPD), not via a metathetic, but rather, via a cationic mechanism. Here, we present a comparison of the reactivity of the two catalytic systems (1 and 1/PA) between themselves and with other systems reported in the literature, the characterization of the polymers formed and mechanistic aspects of the corresponding reactions. PMID- 26670224 TI - Efficient Diethylzinc/Gallic Acid and Diethylzinc/Gallic Acid Ester Catalytic Systems for the Ring-Opening Polymerization of rac-Lactide. AB - Polylactide (PLA) represents one of the most promising biomedical polymers due to its biodegradability, bioresorbability and good biocompatibility. This work highlights the synthesis and characterization of PLAs using novel diethylzinc/gallic acid (ZnEt2/GAc) and diethylzinc/propyl gallate (ZnEt2/PGAc) catalytic systems that are safe for human body. The results of the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in the presence of zinc-based catalytic systems have shown that, depending on the reaction conditions, "predominantly isotactic", disyndiotactic or atactic PLA can be obtained. Therefore, the controlled and stereoselective ROP of rac-LA is discussed in detail in this paper. PMID- 26670225 TI - New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation. AB - 1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl) 1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, 1H-NMR and (13)C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 MUM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents. PMID- 26670226 TI - Chemical Compositions and Insecticidal Activities of Alpinia kwangsiensis Essential Oil against Lasioderma serricorne. AB - The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), beta-pinene (11.15%) and alpha-pinene (10.50%). These four compounds were subsequently isolated and the essential oil and four isolated compounds exhibited potent insecticidal activity against Lasioderma serricorne adults. During the assay, it was shown that the essential oil exhibited both potential contact (LD50 = of 24.59 MUg/adult) and fumigant (LC50 = of 9.91 mg/L air) toxicity against Lasioderma serricorne. The study revealed that the insecticidal activity of the essential oil can be attributed to the synergistic effects of its diverse major components, which indicates that oil of Alpinia kwangsiensis and its isolated compounds have potential to be developed into natural insecticides to control insects in stored grains and traditional Chinese medicinal materials. PMID- 26670227 TI - Bioactive Constituents from the Aerial Parts of Lippia triphylla. AB - Five new compounds, lippianosides A (1), B (2), C (3), D (4), and E (5), along with 26 (6-31) known ones were obtained from the 95% EtOH extract of Lippia triphylla (L. triphylla) aerial parts collected from Rwanda, Africa. Among the known compounds, 11 and 17-30 were isolated from the Lippia genus for the first time. In addition, 12, 13, and 16 were firstly obtained from this species. The structures of them were elucidated by chemical and spectroscopic methods. The antioxidant and triglyceride accumulation inhibition effects of the 31 compounds were examined in L6 cells and HepG2 cells, respectively. PMID- 26670228 TI - The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. AB - Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. PMID- 26670229 TI - Oncogenic MicroRNAs Characterization in Clear Cell Renal Cell Carcinoma. AB - A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR 185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management. PMID- 26670230 TI - Hydrolysis of Oligosaccharides by a Thermostable alpha-Galactosidase from Termitomyces eurrhizus. AB - The genus of Termitomyces purchased from the market has been identified as Termitomyces eurrhizus using the Internal Transcribed Spacer (ITS) method. An alpha-galactosidase from T. eurrhizus (TEG), a monomeric protein with a molecular mass of 72 kDa, was purified 146 fold by employing ion exchange chromatography and gel filtration. The optimum pH and temperature was 5.0 and 60 degrees C, respectively. TEG was stable over pH 2-6, and also exhibited good thermostablility, retaining 100% of the original activity after incubation at 60 degrees C for 2 h. Inhibition of the enzyme activity by N-bromosuccinimide (NBS) constituted evidence for an essential role of tryptophan in the catalytic action of the isolated enzyme. Besides 4-nitro-phenyl alpha-d-galactophyranoside (pNPGal), natural substrates could also be effectively hydrolyzed by TEG. Results of thin-layer chromatography (TLC) revealed complete enzymatic hydrolysis of raffinose and stachyose to galactose at 50 degrees C within 6 h. These properties of TEG advocate its utilization for elevating the nutritional value of soymilk. PMID- 26670231 TI - Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents. AB - We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. PMID- 26670232 TI - Vitamin E Content and Composition in Tomato Fruits: Beneficial Roles and Bio Fortification. AB - Several epidemiological studies have demonstrated that high vitamin E intakes are related to a reduced risk of non-communicable diseases, while other dietary antioxidants are not, suggesting that vitamin E exerts specific healthy functions in addition to its antioxidant role. In this regard, tomato (Solanum lycopersicum), one of the most consumed vegetables of the whole world population, is an important source of both tocopherols and tocotrienols. However, vitamin E content may strongly depend on several biotic and abiotic factors. In this review we will debate the elements affecting the synthesis of tocopherols and tocotrienols in tomato fruit, such as environmental conditions, genotype, fruit maturity level, and the impact of classical processing methods, such as pasteurization and lyophilization on the amount of these compounds. In addition we will analyze the specific vitamin E mechanisms of action in humans and the consequent functional effects derived from its dietary intake. Finally, we will examine the currently available molecular techniques used to increase the content of vitamin E in tomato fruit, starting from the identification of genetic determinants and quantitative trait loci that control the accumulation of these metabolites. PMID- 26670234 TI - Labeled RFS-Based Track-Before-Detect for Multiple Maneuvering Targets in the Infrared Focal Plane Array. AB - The problem of jointly detecting and tracking multiple targets from the raw observations of an infrared focal plane array is a challenging task, especially for the case with uncertain target dynamics. In this paper a multi-model labeled multi-Bernoulli (MM-LMB) track-before-detect method is proposed within the labeled random finite sets (RFS) framework. The proposed track-before-detect method consists of two parts-MM-LMB filter and MM-LMB smoother. For the MM-LMB filter, original LMB filter is applied to track-before-detect based on target and measurement models, and is integrated with the interacting multiple models (IMM) approach to accommodate the uncertainty of target dynamics. For the MM-LMB smoother, taking advantage of the track labels and posterior model transition probability, the single-model single-target smoother is extended to a multi-model multi-target smoother. A Sequential Monte Carlo approach is also presented to implement the proposed method. Simulation results show the proposed method can effectively achieve tracking continuity for multiple maneuvering targets. In addition, compared with the forward filtering alone, our method is more robust due to its combination of forward filtering and backward smoothing. PMID- 26670233 TI - Monosodium Urate Crystal-Induced Chondrocyte Death via Autophagic Process. AB - Monosodium urate (MSU) crystals, which are highly precipitated in the joint cartilage, increase the production of cartilage-degrading enzymes and pro inflammatory mediators in cartilage, thereby leading to gouty inflammation and joint damage. In this study, we investigated the effect of MSU crystals on the viability of human articular chondrocytes and the mechanism of MSU crystal induced chondrocyte death. MSU crystals significantly decreased the viability of primary chondrocytes in a time- and dose-dependent manner. DNA fragmentation was observed in a culture medium of MSU crystal-treated chondrocytes, but not in cell lysates. MSU crystals did not activate caspase-3, a marker of apoptosis, compared with actinomycin D and TNF-alpha-treated cells. MSU crystals did not directly affect the expression of endoplasmic reticulum (ER) stress markers at the mRNA and protein levels. However, MSU crystals significantly increased the LC3-II level in a time-dependent manner, indicating autophagy activation. Moreover, MSU crystal-induced autophagy and subsequent chondrocyte death were significantly inhibited by 3-methyladenine, a blocker of autophagosomes formation. MSU crystals activated autophagy via inhibition of phosporylation of the Akt/mTOR signaling pathway. These results demonstrate that MSU crystals may cause the death of chondrocytes through the activation of the autophagic process rather than apoptosis or ER stress. PMID- 26670235 TI - DOA Estimation under Unknown Mutual Coupling and Multipath with Improved Effective Array Aperture. AB - Subspace-based high-resolution direction of arrival (DOA) estimation significantly deteriorates under array manifold perturbation and rank deficiency of the covariance matrix due to mutual coupling and multipath propagation, respectively. In this correspondence, the unknown mutual coupling can be circumvented by the proposed method without any passive or active calibration process, and the DOA of the coherent signals can be accurately estimated accordingly. With a newly constructed matrix, the deficient rank can be restored, and the effective array aperture can be extended compared with conventional spatial smoothing. The proposed method achieves a good robustness and DOA estimation accuracy with unknown mutual coupling. The simulation results demonstrate the validity and efficiency of the proposed method. PMID- 26670236 TI - Associations Between Excessive Sodium Intake and Smoking and Alcohol Intake Among Korean Men: KNHANES V. AB - In this study, we evaluated the associations of smoking and alcohol intake, both independently and collectively, with sodium intake in Korean men. Subjects (6340 men) were from the fifth Korean National Health Examination Survey (2010-2012). Smoking-related factors included smoking status, urinary cotinine level, and pack years of smoking. Food intake was assessed using a 24-h recall. The odds of excessive sodium intake were estimated using survey logistic regression analysis. The smoking rate was 44.1%. The geometric mean of the urinary cotinine level was 0.05 ug/mL, and the median (min-max) pack-years of smoking was 13.2 (0-180). When adjusted for related factors, the odds (95% confidence interval) of excessive sodium intake were 1.54 (1.00, 2.37), 1.55 (1.23, 1.94), 1.44 (1.07, 1.95), and 1.37 (1.11, 1.68) times higher in the group exposed to smoking and drinking than in the group that never smoked nor drank, the group that never smoked and drank <5 times per month, the group that did not currently smoke and never drank, and the group that did not currently smoke or drink <5 times per month, respectively. There was an interaction effect between smoking and alcohol intake (p-interaction = 0.02). The results suggest that simultaneous exposure to smoking and alcohol intake is associated with increased odds of excessive sodium intake. PMID- 26670237 TI - Screening for Infectious Diseases among Newly Arrived Migrants: Experiences and Practices in Non-EU Countries of the Mediterranean Basin and Black Sea. AB - Changing migration dynamics in the Mediterranean Sea and differences in infectious diseases (ID) burden between the countries of origin have raised questions whether public health actions are needed to avoid the transmission of ID. Screening newly arrived migrants for ID is one health monitoring option, offering opportunities for prevention, early detection and treatment. The authors conducted a survey among country experts in non-European Union countries of the Mediterranean and Black Sea, in order to explore current ID screening practices and policies for newly arrived migrants. The association between the existence of guidelines and the proportion of refugees in the population was also estimated. Eighteen country experts responded (90%) out of the 20 invited. Eleven countries (61%) implemented screening programmes and six (38%) had national guidelines. Screening was performed most often for tuberculosis at the holding level. A higher proportion of refugees in the population was associated with the existence of guidelines for screening (p = 0.05). Fourteen experts (88%) considered screening among migrants useful. The results show that screening for ID in newly arrived migrants is relevant for non-EU countries of the Mediterranean and Black Sea. Common guidelines could be promoted focusing on both individual and public health benefits of screening programmes. PMID- 26670238 TI - Waterpipe Tobacco Smoking in Turkey: Policy Implications and Trends from the Global Adult Tobacco Survey (GATS). AB - Waterpipe tobacco smoking (WTS) is an emerging tobacco product globally, especially among adolescents and young adults who may perceive WTS as a safe alternative to smoking cigarettes. Monitoring the use of WTS in Turkey in relation to the tobacco control policy context is important to ensure that WTS does not become a major public health issue in Turkey. The Global Adult Tobacco Survey (GATS) was conducted in Turkey in 2008 and was repeated in 2012. GATS provided prevalence estimates on current WTS and change over time. Other indicators of WTS were also obtained, such as age of initiation and location of use. Among persons aged 15 and older in Turkey, the current prevalence of WTS decreased from 2.3% in 2008 to 0.8% in 2012, representing a 65% relative decline. Among males, WTS decreased from 4.0% to 1.1% (72% relative decline). While the overall smoking prevalence decreased among females, there was no change in the rate of WTS (0.7% in 2008 vs. 0.5% in 2012), though the WTS prevalence rate was already low in 2008. Comprehensive tobacco control efforts have been successful in reducing the overall smoking prevalence in Turkey, which includes the reduction of cigarette smoking and WTS. However, it is important to continue monitoring the use of waterpipes in Turkey and targeting tobacco control efforts to certain groups that may be vulnerable to future WTS marketing (e.g., youth, women). PMID- 26670239 TI - Changes in the Effect of Heat on Mortality in the Last 20 Years in Nine European Cities. Results from the PHASE Project. AB - The European project PHASE aims to evaluate patterns of change in the temperature mortality relationship and in the number of deaths attributable to heat in nine European cities in two periods, before and after summer 2003 (1996-2002 and 2004 2010). We performed age-specific Poisson regression models separately in the two periods, controlling for seasonality, air pollution and time trends. Distributed lag non-linear models were used to estimate the Relative Risks of daily mortality for increases in mean temperature from the 75th to 99th percentile of the summer distribution for each city. In the recent period, a reduction in the mortality risk associated to heat was observed only in Athens, Rome and Paris, especially among the elderly. Furthermore, in terms of heat-attributable mortality, 985, 787 and 623 fewer deaths were estimated, respectively, in the three cities. In Helsinki and Stockholm, there is a suggestion of increased heat effect. Noteworthy is that an effect of heat was still present in the recent years in all cities, ranging from +11% to +35%. In Europe, considering the warming observed in recent decades and population ageing, effective intervention measures should be promoted across countries, especially targeting vulnerable subgroups of the population with lower adaptive resources. PMID- 26670240 TI - Heavy Metal Contamination in Rice-Producing Soils of Hunan Province, China and Potential Health Risks. AB - We studied Cd, Cr, As, Ni, Mn, Pb, and Hg in three agricultural areas of Hunan province and determined the potential non-carcinogenic and carcinogenic risks for residents. Soil and brown rice samples from Shimen, Fenghuang, and Xiangtan counties were analyzed by atomic absorption spectroscopy. Soil levels of Cd and Hg were greatest, followed by As and Ni. The mean concentrations of heavy metals in brown rice were Cd 0.325, Cr 0.109, As 0.344, Ni 0.610, Mn 9.03, Pb 0.023, and Hg 0.071 mg/kg, respectively. Cd and Hg had greater transfer ability from soil to rice than the other elements. Daily intake of heavy metals through brown rice consumption were estimated to be Cd 2.30, Cr 0.775, As 2.45, Ni 4.32, Pb 0.162, Mn 64.6 and Hg 0.503 ug/(kg.day), respectively. Cd, Hg and As Hazard Quotient values were greater than 1 and Cd, Cr, As and Ni Cancer Risk values were all greater than 10(-4). The total non-carcinogenic risk factor was 14.6 and the total carcinogenic risk factor was 0.0423. Long-term exposure to heavy metals through brown rice consumption poses both potential non-carcinogenic and carcinogenic health risks to the local residents. PMID- 26670241 TI - Socio Economic Status and Traumatic Brain Injury amongst Pediatric Populations: A Spatial Analysis in Greater Vancouver. AB - INTRODUCTION: Within Canada, injuries are the leading cause of death amongst children fourteen years of age and younger, and also one of the leading causes of morbidity. Low Socio Economic Status (SES) seems to be a strong indicator of a higher prevalence of injuries. This study aims to identify hotspots for pediatric Traumatic Brain Injury (TBI) and examines the relationship between SES and pediatric TBI rates in greater Vancouver, British Columbia (BC), Canada. METHODS: Pediatric TBI data from the BC Trauma Registry (BCTR) was used to identify all pediatric TBI patients admitted to BC hospitals between the years 2000 and 2013. Spatial analysis was used to identify hotspots for pediatric TBI. Multivariate analysis was used to distinguish census variables that were correlated with rates of injury. RESULTS: Six hundred and fifty three severe pediatric TBI injuries occurred within the BC Lower Mainland between 2000 and 2013. High rates of injury were concentrated in the East, while low rate clusters were most common in the West of the region (more affluent neighborhoods). A low level of education was the main predictor of a high rate of injury (OR = 1.13, 95% CI = 1.03-1.23, p Value 0.009). CONCLUSION: While there was a clear relationship between different SES indicators and pediatric TBI rates in greater Vancouver, income-based SES indicators did not serve as good predictors within this region. PMID- 26670242 TI - Comparison of Highly Resolved Model-Based Exposure Metrics for Traffic-Related Air Pollutants to Support Environmental Health Studies. AB - Human exposure to air pollution in many studies is represented by ambient concentrations from space-time kriging of observed values. Space-time kriging techniques based on a limited number of ambient monitors may fail to capture the concentration from local sources. Further, because people spend more time indoors, using ambient concentration to represent exposure may cause error. To quantify the associated exposure error, we computed a series of six different hourly-based exposure metrics at 16,095 Census blocks of three Counties in North Carolina for CO, NO(x), PM(2.5), and elemental carbon (EC) during 2012. These metrics include ambient background concentration from space-time ordinary kriging (STOK), ambient on-road concentration from the Research LINE source dispersion model (R-LINE), a hybrid concentration combining STOK and R-LINE, and their associated indoor concentrations from an indoor infiltration mass balance model. Using a hybrid-based indoor concentration as the standard, the comparison showed that outdoor STOK metrics yielded large error at both population (67% to 93%) and individual level (average bias between -10% to 95%). For pollutants with significant contribution from on-road emission (EC and NO(x)), the on-road based indoor metric performs the best at the population level (error less than 52%). At the individual level, however, the STOK-based indoor concentration performs the best (average bias below 30%). For PM(2.5), due to the relatively low contribution from on-road emission (7%), STOK-based indoor metric performs the best at both population (error below 40%) and individual level (error below 25%). The results of the study will help future epidemiology studies to select appropriate exposure metric and reduce potential bias in exposure characterization. PMID- 26670243 TI - Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa. AB - Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms. PMID- 26670244 TI - Structure of the Receptor-Binding Carboxy-Terminal Domain of the Bacteriophage T5 L-Shaped Tail Fibre with and without Its Intra-Molecular Chaperone. AB - Bacteriophage T5, a Siphovirus belonging to the order Caudovirales, has a flexible, three-fold symmetric tail, to which three L-shaped fibres are attached. These fibres recognize oligo-mannose units on the bacterial cell surface prior to infection and are composed of homotrimers of the pb1 protein. Pb1 has 1396 amino acids, of which the carboxy-terminal 133 residues form a trimeric intra-molecular chaperone that is auto-proteolyzed after correct folding. The structure of a trimer of residues 970-1263 was determined by single anomalous dispersion phasing using incorporated selenomethionine residues and refined at 2.3 A resolution using crystals grown from native, methionine-containing, protein. The protein inhibits phage infection by competition. The phage-distal receptor-binding domain resembles a bullet, with the walls formed by partially intertwined beta-sheets, conferring stability to the structure. The fold of the domain is novel and the topology unique to the pb1 structure. A site-directed mutant (Ser1264 to Ala), in which auto-proteolysis is impeded, was also produced, crystallized and its 2.5 A structure solved by molecular replacement. The additional chaperone domain (residues 1263-1396) consists of a central trimeric alpha-helical coiled-coil flanked by a mixed alpha-beta domain. Three long beta-hairpin tentacles, one from each chaperone monomer, extend into long curved grooves of the bullet-shaped domain. The chaperone-containing mutant did not inhibit infection by competition. PMID- 26670245 TI - Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines. AB - Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family, which also includes viruses such as polioviruses. EV71, together with coxsackieviruses, is widely known for its association with Hand Foot Mouth Disease (HFMD), which generally affects children age five and below. Besides HFMD, EV71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. Considering the lack of a vaccine and antiviral drug against EV71, together with the increasing spread of these viruses, the development of such drugs and vaccines becomes the top priority in protecting our younger generations. This article, hence, reviews some of the recent progress in the formulations of anti-therapeutics and vaccine generation for EV71, covering (i) inactivated vaccines; (ii) baculovirus-expressed vaccines against EV71; (iii) human intravenous immunoglobulin (IVIg) treatment; and (iv) the use of monoclonal antibody therapy as a prevention and treatment for EV71 infections. PMID- 26670246 TI - Two Cytoplasmic Acylation Sites and an Adjacent Hydrophobic Residue, but No Other Conserved Amino Acids in the Cytoplasmic Tail of HA from Influenza A Virus Are Crucial for Virus Replication. AB - Recruitment of the matrix protein M1 to the assembly site of the influenza virus is thought to be mediated by interactions with the cytoplasmic tail of hemagglutinin (HA). Based on a comprehensive sequence comparison of all sequences present in the database, we analyzed the effect of mutating conserved residues in the cytosol-facing part of the transmembrane region and cytoplasmic tail of HA (A/WSN/33 (H1N1) strain) on virus replication and morphology of virions. Removal of the two cytoplasmic acylation sites and substitution of a neighboring isoleucine by glutamine prevented rescue of infectious virions. In contrast, a conservative exchange of the same isoleucine, non-conservative exchanges of glycine and glutamine, deletion of the acylation site at the end of the transmembrane region and shifting it into the tail did not affect virus morphology and had only subtle effects on virus growth and on the incorporation of M1 and Ribo-Nucleoprotein Particles (RNPs). Thus, assuming that essential amino acids are conserved between HA subtypes we suggest that, besides the two cytoplasmic acylation sites (including adjacent hydrophobic residues), no other amino acids in the cytoplasmic tail of HA are indispensable for virus assembly and budding. PMID- 26670247 TI - Bacteriophage Mediates Efficient Gene Transfer in Combination with Conventional Transfection Reagents. AB - The development of commercially available transfection reagents for gene transfer applications has revolutionized the field of molecular biology and scientific research. However, the challenge remains in ensuring that they are efficient, safe, reproducible and cost effective. Bacteriophage (phage)-based viral vectors have the potential to be utilized for general gene transfer applications within research and industry. Yet, they require adaptations in order to enable them to efficiently enter cells and overcome mammalian cellular barriers, as they infect bacteria only; furthermore, limited progress has been made at increasing their efficiency. The production of a novel hybrid nanocomplex system consisting of two different nanomaterial systems, phage vectors and conventional transfection reagents, could overcome these limitations. Here we demonstrate that the combination of cationic lipids, cationic polymers or calcium phosphate with M13 bacteriophage-derived vectors, engineered to carry a mammalian transgene cassette, resulted in increased cellular attachment, entry and improved transgene expression in human cells. Moreover, addition of a targeting ligand into the nanocomplex system, through genetic engineering of the phage capsid further increased gene expression and was effective in a stable cell line generation application. Overall, this new hybrid nanocomplex system (i) provides enhanced phage-mediated gene transfer; (ii) is applicable for laboratory transfection processes and (iii) shows promise within industry for large-scale gene transfer applications. PMID- 26670248 TI - Magnesium and Space Flight. AB - Magnesium is an essential nutrient for muscle, cardiovascular, and bone health on Earth, and during space flight. We sought to evaluate magnesium status in 43 astronauts (34 male, 9 female; 47 +/- 5 years old, mean +/- SD) before, during, and after 4-6-month space missions. We also studied individuals participating in a ground analog of space flight (head-down-tilt bed rest; n = 27 (17 male, 10 female), 35 +/- 7 years old). We evaluated serum concentration and 24-h urinary excretion of magnesium, along with estimates of tissue magnesium status from sublingual cells. Serum magnesium increased late in flight, while urinary magnesium excretion was higher over the course of 180-day space missions. Urinary magnesium increased during flight but decreased significantly at landing. Neither serum nor urinary magnesium changed during bed rest. For flight and bed rest, significant correlations existed between the area under the curve of serum and urinary magnesium and the change in total body bone mineral content. Tissue magnesium concentration was unchanged after flight and bed rest. Increased excretion of magnesium is likely partially from bone and partially from diet, but importantly, it does not come at the expense of muscle tissue stores. While further study is needed to better understand the implications of these findings for longer space exploration missions, magnesium homeostasis and tissue status seem well maintained during 4-6-month space missions. PMID- 26670249 TI - Dietary Carbohydrate and Nocturnal Sleep Duration in Relation to Children's BMI: Findings from the IDEFICS Study in Eight European Countries. AB - Previous research has found an association between being overweight and short sleep duration. We hypothesized that this association could be modified by a high carbohydrate (HC) diet and that the timing and type (starch or sugar) of intake may be an important factor in this context. Participants in the prospective, eight-country European study IDEFICS were recruited from September 2007 to June 2008, when they were aged two to nine years. Data on lifestyle, dietary intake and anthropometry were collected on two occasions. This study included 5944 children at baseline and 4301 at two-year follow-up. For each meal occasion (morning, midday, and evening), starch in grams and sugar in grams were divided by total energy intake (EI), and quartiles calculated. HC-starch and HC-sugar intake categories were defined as the highest quartile for each meal occasion. In a mutually adjusted linear regression model, short sleep duration as well as HC starch in the morning were positively associated with body mass index (BMI) z scores at baseline. HC-starch at midday was positively associated with body mass index (BMI) z-scores in children with short sleep duration, and negatively associated with BMI z-scores in those with normal sleep. After adjustment for baseline BMI z-scores, associations between total HC from starch or sugar and high BMI z-scores at two-year follow-up did not persist. Our observations offer a perspective on optimal timing for macronutrient consumption, which is known to be influenced by circadian rhythms. Reduced carbohydrate intake, especially during morning and midday meals, and following nocturnal sleep duration recommendations are two modifiable factors that may protect children from being overweight in the future. PMID- 26670250 TI - Fermented Brown Rice and Rice Bran with Aspergillus oryzae (FBRA) Prevents Inflammation-Related Carcinogenesis in Mice, through Inhibition of Inflammatory Cell Infiltration. AB - We have established an inflammation-related carcinogenesis model in mouse, in which regressive QR-32 cells subcutaneously co-implanted with a foreign body gelatin sponge-convert themselves into lethal tumors due to massive infiltration of inflammatory cells into the sponge. Animals were fed with a diet containing 5% or 10% fermented brown rice and rice bran with Aspergillus oryzae (FBRA). In 5% and 10% FBRA diet groups, tumor incidences were lower (35% and 20%, respectively) than in the non-treated group (70%). We found that FBRA reduced the number of inflammatory cells infiltrating into the sponge. FBRA administration did not cause myelosuppression, which indicated that the anti-inflammatory effects of FBRA took place at the inflammatory lesion. FBRA did not have antitumor effects on the implanted QRsP-11 tumor cells, which is a tumorigenic cell line established from a tumor arisen after co-implantation of QR-32 cells with sponge. FBRA did not reduce formation of 8-hydroxy-2'-deoxyguanine adducts, a marker of oxidative DNA damage in the inflammatory lesion; however, it reduced expression of inflammation-related genes such as TNF-alpha, Mac-1, CCL3 and CXCL2. These results suggest that FBRA will be an effective chemopreventive agent against inflammation-related carcinogenesis that acts by inhibiting inflammatory cell infiltration into inflammatory lesions. PMID- 26670251 TI - Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe. AB - Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID- 26670252 TI - Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model. AB - Staphylococcus aureus, the most common cause of wound infection, produces several exotoxins, including superantigens (SAgs). SAgs are the potent activators of the immune system. Given this unique property, we hypothesized that SAgs produced by S. aureus in wounds would have local, as well as systemic immunologic effects. We tested our hypothesis using a novel staphylococcal skin wound infection model in transgenic mice expressing HLA-DR3. Skin wounds were left uninfected or colonized with S. aureus strains producing SAgs or an isogenic strain not producing any SAg. Animals with wounds challenged with SAg-producing S. aureus had increased morbidity and lower serum IL-17 levels compared to those challenged with the SAg non-producing S. aureus (p = 0.027 and p = 0.032, respectively). At Day 8 following microbial challenge, compared to mice with uninfected wounds, the proportion of Vbeta8+CD4+ T cells was increased, while the proportion of Vbeta8+CD8+ T cells was decreased only in the spleens of mice challenged with SAg producing S. aureus (p < 0.001). No such changes were measured in mice challenged with SAg non-producing S. aureus. Lungs, livers and kidneys from mice challenged with SAg-producing, but not SAg non-producing, S. aureus showed inflammatory changes. Overall, SAg-mediated systemic immune activation in wounds harboring S. aureus may have clinical implications. PMID- 26670253 TI - Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction. AB - Botulinum neurotoxins (BoNTs) and some animal neurotoxins (beta-Bungarotoxin, beta-Btx, from elapid snakes and alpha-Latrotoxin, alpha-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. PMID- 26670254 TI - New Invertebrate Vectors of Okadaic Acid from the North Atlantic Waters--Portugal (Azores and Madeira) and Morocco. AB - Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, Sao Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues. PMID- 26670255 TI - Loss of E2F1 Extends Survival and Accelerates Oral Tumor Growth in HPV-Positive Mice. AB - The Human Papillomavirus (HPV) is associated with several human cancers, including head and neck squamous cell carcinomas (HNSCCs). HPV expresses the viral oncogene E7 that binds to the retinoblastoma protein (RB1) in order to activate the E2F pathway. RB1 can mediate contradictory pathways-cell growth and cell death via E2F family members. Here, we assessed the extent to which E2F1 mediates lethality of HPV oncogenes. Ubiquitous expression of the HPV oncogenes E6 and E7 caused lethality in mice that was associated with focal necrosis in hepatocytes and pancreatic tissues. Furthermore, all organs expressing HPV oncogenes displayed up-regulation of several E2F1 target genes. The E2F1 pathway mediated lethality in HPV-positive mice because deletion of E2F1 increased survival of mice ubiquitously expressing HPV oncogenes. E2F1 similarly functioned as a tumor suppressor in HPV-positive oral tumors as tumors grew faster with homozygous loss of E2F1 compared to tumors with heterozygous loss of E2F1. Re expression of E2F1 caused decreased clonogenicity in HPV-positive cancer cells. Our results indicate that HPV oncogenes activated the E2F1 pathway to cause lethality in normal mice and to suppress oral tumor growth. These results suggest that selective modulation of the E2F1 pathway, which is activated in HPV tumors, may facilitate tumor regression. PMID- 26670256 TI - Exploring Folate Diversity in Wild and Primitive Potatoes for Modern Crop Improvement. AB - Malnutrition is one of the world's largest health concerns. Folate (also known as vitamin B9) is essential in the human diet, and without adequate folate intake, several serious health concerns, such as congenital birth defects and an increased risk of stroke and heart disease, can occur. Most people's folate intake remains sub-optimal, even in countries that have a folic acid food fortification program in place. Staple crops, such as potatoes, represent an appropriate organism for biofortification through traditional breeding based on their worldwide consumption and the fact that modern cultivars only contain about 6% of the daily recommended intake of folate. To start breeding potatoes with enhanced folate content, high folate potato material must be identified. In this study, 250 individual plants from 77 accessions and 10 Solanum species were screened for their folate content using a tri-enzyme extraction and microbial assay. There was a 10-fold range of folate concentrations among individuals. Certain individuals within the species Solanum tuberosum subsp. andigenum, Solanum vernei and Solanum boliviense have the potential to produce more than double the folate concentrations of commercial cultivars, such as Russet Burbank. Our results show that tapping into the genetic diversity of potato is a promising approach to increase the folate content of this important crop. PMID- 26670258 TI - The Effect of Platinum Electrocatalyst on Membrane Degradation in Polymer Electrolyte Fuel Cells. AB - Membrane degradation is a severe factor limiting the lifetime of polymer electrolyte fuel cells. Therefore, obtaining a deeper knowledge is fundamental in order to establish fuel cells as competitive product. A segmented single cell was operated under open circuit voltage with alternating relative humidity. The influence of the catalyst layer on membrane degradation was evaluated by measuring a membrane without electrodes and a membrane-electrode-assembly under identical conditions. After 100 h of accelerated stress testing the proton conductivity of membrane samples near the anode and cathode was investigated by means of ex situ electrochemical impedance spectroscopy. The membrane sample near the cathode inlet exhibited twofold lower membrane resistance and a resulting twofold higher proton conductivity than the membrane sample near the anode inlet. The results from the fluoride ion analysis have shown that the presence of platinum reduces the fluoride emission rate; which supports conclusions drawn from the literature. PMID- 26670260 TI - Corrigendum. PMID- 26670257 TI - Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification. AB - Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID- 26670259 TI - Extraction of Gold(III) from Hydrochloric Acid Solutions with a PVC-based Polymer Inclusion Membrane (PIM) Containing Cyphos((r)) IL 104. AB - Poly(vinyl chloride) (PVC) based polymer inclusion membranes (PIMs), with different concentrations of Cyphos(r) IL 104 as the membrane extractant/carrier, were studied for their ability to extract Au(III) from hydrochloric acid solutions. Some of the PIMs also contained one of the following plasticizers or modifiers: 2-nitrophenyloctyl ether, dioctylphthalate, 1-dodecanol, 1 tetradecanol, or tri(2-ethylhexyl) phosphate. The best performance, in terms of extraction rate and amount of Au(III) extracted, was exhibited by a PIM consisting of 25 wt% Cyphos((r)) IL 104, 5 wt% 1-dodecanol, and 70 wt% PVC. An almost complete back-extraction of the Au(III) extracted from this membrane was achieved by using a 0.10 mol L(-1) Na2SO3 receiver solution at pH 8. The stoichiometry of the extracted Au(III)/Cyphos(r) IL 104 adduct was determined as [P]+ [AuCl4](-) H+ [PO2](-) where [P]+ and [PO2](-) represent trihexyl(tetradecyl) phosphonium and bis(2,4,4-trimethylpentyl) phosphinate ions, respectively. Back-extraction of Au(III) is suggested to occur by reduction of Au(III) to Au(I), with the formation of the species [Au(SO3)2](3-) in the aqueous receiver solution. Loss of 1-dodecanol from the newly developed PIM to the aqueous solutions in contact with it was observed, which indicated that this membrane was suitable for single use in the efficient recovery of Au(III) from hydrochloric acid solutions of electronic scrap or recycled jewelry. PMID- 26670261 TI - Cognitive inhibition in depression and suicidal behavior: a neuroimaging study. AB - BACKGROUND: Cognitive inhibition deficits have previously been found in suicide attempters. This study examined the neural basis for these deficits in depressed patients with and without a history of suicidal behavior. METHOD: Functional magnetic resonance imaging was used to measure brain activation during the Go/No Go response inhibition task in 25 unmedicated and depressed middle-aged suicide attempters, 22 unmedicated depressed patient controls with no personal or family history of suicidal behavior, and 27 healthy controls. Whole-brain analyses were conducted with SPM12. RESULTS: Suicide attempters exhibited an elevated number of commission errors relative to both control groups. However, suicide attempters did not differ from patient controls in terms of brain activation for any contrast. Analyses showed a significant association between depression and brain activation in the left inferior frontal gyrus and medial thalamus during Go v. No Go, and in the bilateral parietal cortex and left orbitofrontal cortex during No Go v. baseline. These regions were correlated with psychological pain, suicidal ideation and global functioning. There was no association between brain activation and personal histories of suicidal act. CONCLUSIONS: Our study suggests that deficits in cognitive inhibition, in relation to the inferior frontal gyrus, thalamus, orbitofrontal cortex and parietal cortex, are related to the depressive state and not specifically to suicide vulnerability. We hypothesize that state-related deficits may add to trait-like cognitive impairments to facilitate suicidal acts. These different types of cognitive impairments may necessitate different therapeutic strategies for the prevention of suicide. PMID- 26670262 TI - Radical evolution: the 2015 Difficult Airway Society guidelines for managing unanticipated difficult or failed tracheal intubation. AB - There is little doubt that these guidelines incorporate advances made in airway management since 2004. They will change day-to-day practice of anaesthesia, as outlined above, from pre-operative airway assessment, to integrating the WHO team briefing, to the use and provision of equipment and drugs, and the recording of information on the anaesthesia chart. They will inform the later analysis of any critical airway incidents, especially as documentation and postoperative management are addressed, and they will encourage training in a range of techniques. Taken together, not quite a revolution but certainly a very 'radical evolution'.Assessment of the utility of the new guidelines should consider if they can be used as tools to enhance knowledge and training, or in addition as a prosthesis to bridge the gap between the requirements of and our abilities during emergencies. Formal testing may reveal which aspects of their design, complex as it is, may distract from, rather than enhance, airway management during crises.All guidelines represent a standard of care or a normative approach to a clinical problem. As such, they not only help guide clinicians, but they also provide the broader community with the opportunity to improve standards, to ensure equipment is available, and that training for the skills and processes required are in place to ensure successful adoption. PMID- 26670264 TI - Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV. AB - 2-Aminoquinazolin-4(3H)-ones were identified as a novel class of malaria digestive vacuole plasmepsin inhibitors by using NMR-based fragment screening against Plm II. Initial fragment hit optimization led to a submicromolar inhibitor, which was cocrystallized with Plm II to produce an X-ray structure of the complex. The structure showed that 2-aminoquinazolin-4(3H)-ones bind to the open flap conformation of the enzyme and provided clues to target the flap pocket. Further improvement in potency was achieved via introduction of hydrophobic substituents occupying the flap pocket. Most of the 2-aminoquinazolin 4(3H)-one based inhibitors show a similar activity against digestive Plms I, II, and IV and >10-fold selectivity versus CatD, although varying the flap pocket substituent led to one Plm IV selective inhibitor. In cell-based assays, the compounds show growth inhibition of Plasmodium falciparum 3D7 with IC50 ~ 1 MUM. Together, these results suggest 2-aminoquinazolin-4(3H)-ones as perspective leads for future development of an antimalarial agent. PMID- 26670265 TI - Experience-based co-design in an adult psychological therapies service. AB - BACKGROUND: Experience-based co-design (EBCD) is a methodology for service improvement and development, which puts service-user voices at the heart of improving health services. AIMS: The aim of this paper was to implement the EBCD methodology in a mental health setting, and to investigate the challenges which arise during this process. METHOD: In order to achieve this, a modified version of the EBCD methodology was undertaken, which involved listening to the experiences of the people who work in and use the mental health setting and sharing these experiences with the people who could effect change within the service, through collaborative work between service-users, staff and managers. RESULTS: EBCD was implemented within the mental health setting and was well received by service-users, staff and stakeholders. A number of modifications were necessary in this setting, for example high levels of support available to participants. CONCLUSIONS: It was concluded that EBCD is a suitable methodology for service improvement in mental health settings. PMID- 26670267 TI - Three worlds of health technology assessment: explaining patterns of diffusion of HTA agencies in Europe. AB - In the past two decades, setting up independent health technology assessment (HTA) agencies has become a popular tool to inform reimbursement decision-making in health care, spreading from Northern European countries across Western Europe but much less so to post-communist countries. Structural political science explanations leave gaps in clarifying this diffusion pattern. This paper proposes a theoretical model focusing on the influence of domestic epistemic communities mitigating policy diffusion. Based on a review of HTA institutions in the EU, it proposes a chronological taxonomy of HTA agencies in Europe (the forerunners, the mainstreamers and the non-adopters) and asks why there is such an important East West divide. The paper discusses theoretical explanations from different literatures, finding unsatisfactory many traditional political science answers such as the degree of centralization of a country's health system, its financial organization (Bismarckian or Beveridgian), the attitude toward independent regulatory bodies in general, the influence of international actors, or lack of resources. Finally, it suggests cases for empirical testing of the domestic epistemic communities model. PMID- 26670263 TI - A human haploid gene trap collection to study lncRNAs with unusual RNA biology. AB - Many thousand long non-coding (lnc) RNAs are mapped in the human genome. Time consuming studies using reverse genetic approaches by post-transcriptional knock down or genetic modification of the locus demonstrated diverse biological functions for a few of these transcripts. The Human Gene Trap Mutant Collection in haploid KBM7 cells is a ready-to-use tool for studying protein-coding gene function. As lncRNAs show remarkable differences in RNA biology compared to protein-coding genes, it is unclear if this gene trap collection is useful for functional analysis of lncRNAs. Here we use the uncharacterized LOC100288798 lncRNA as a model to answer this question. Using public RNA-seq data we show that LOC100288798 is ubiquitously expressed, but inefficiently spliced. The minor spliced LOC100288798 isoforms are exported to the cytoplasm, whereas the major unspliced isoform is nuclear localized. This shows that LOC100288798 RNA biology differs markedly from typical mRNAs. De novo assembly from RNA-seq data suggests that LOC100288798 extends 289kb beyond its annotated 3' end and overlaps the downstream SLC38A4 gene. Three cell lines with independent gene trap insertions in LOC100288798 were available from the KBM7 gene trap collection. RT-qPCR and RNA-seq confirmed successful lncRNA truncation and its extended length. Expression analysis from RNA-seq data shows significant deregulation of 41 protein-coding genes upon LOC100288798 truncation. Our data shows that gene trap collections in human haploid cell lines are useful tools to study lncRNAs, and identifies the previously uncharacterized LOC100288798 as a potential gene regulator. PMID- 26670268 TI - Synthesis and Fluorescence Properties of Pyrimidine-Based Diboron Complexes with Donor-pi-Acceptor Structures. AB - Pyrimidine-based diboron complexes bearing beta-iminoenolate ligands and phenyl groups as bulky substituents on the boron atoms were synthesized as novel fluorescent dyes, and their fluorescence properties were investigated in solution and in the solid state. The diboron complexes with donor-pi-acceptor structures showed positive solvatochromism in the fluorescence spectra. The cyano derivative exhibited the most dramatic redshift of the fluorescence maximum Fmax with increasing solvent polarity (from 551 nm in n-hexane to 710 nm in acetonitrile). The diboron complexes showed solid-state fluorescence in the range of 578-706 nm with fluorescence quantum yields of 0.06-0.28. Additionally, the trifluoromethyl derivative exhibited solvent-inclusion solid-state fluorescence. The trifluoromethyl derivative formed toluene-inclusion and ethyl acetate-inclusion crystals. The toluene-inclusion crystal (Fmax = 668 nm, Phif = 0.16) showed a blueshifted Fmax and higher Phif value compared to the original trifluoromethyl derivative (Fmax = 694 nm, Phif = 0.08) in the solid state. On the other hand, the Fmax (709 nm) and Phif (0.04) values of the ethyl acetate-inclusion crystal were redshifted and lower, respectively. PMID- 26670274 TI - Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn's Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab. AB - OBJECTIVE: In patients with postoperative recurrence of Crohn's disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses. DESIGN: Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn's Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0-1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn's disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy. RESULTS: Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean+/-SE: 2.0+/-0.3 vs 4.75+/ 0.83 MUg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects. CONCLUSIONS: Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment. PMID- 26670276 TI - CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus. AB - The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9 mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications. PMID- 26670275 TI - A shortened verbal autopsy instrument for use in routine mortality surveillance systems. AB - BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach. METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates. RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively. CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems. PMID- 26670277 TI - In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation. AB - MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC), among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3' untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC. PMID- 26670278 TI - High-efficiency Generation of Multiple Short Noncoding RNA in B-cells and B-cell derived Extracellular Vesicles. AB - Short noncoding (snc)RNAs are important new players in the landscape of biologics with therapeutic potential. Recently, we reported on a new method for the synthesis and delivery of snc RNA in B-cells transfected with plasmid DNA. Here using the same approach, we demonstrate that B-cells can be programmed for the enforced biogenesis and synchronous release of multiple sncRNAs. Our data show that this goal is feasible and that multiple sncRNA are released in the extracellular compartment in amounts comparable to those from B-cells programmed to express and secrete one scnRNA only. Furthermore, we found that the cargo of extracellular vescicles (EVs) isolated from programmed B-cells is remarkably enriched for multiple sncRNA. On average, we found that the content of multiple sncRNAs in EVs is 3.6 copynumber/EV. Collectively, we demonstrate that B-cells can be easily programmed toward the synthesis and release of multiple sncRNAs, including sncRNA-laden EVs, efficiently and specifically. PMID- 26670279 TI - Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy. AB - The development of a safeguard system to remove tumorigenic cells would allow safer clinical applications of stem cells for the treatment of patients with an intractable disease including genetic disorders. Such safeguard systems should not disrupt the host genome and should have long-term stability. Here, we attempted to develop a tumor-suppressing mammalian artificial chromosome containing a safeguard system that uses the immune rejection system against allogeneic tissue from the host. For proof-of-concept of the safeguard system, B16F10 mouse melanoma cells expressing the introduced H2-K(d) major histocompatibility complex (MHC class I)-allogenic haplotype were transplanted into recipient C57BL/6J mice expressing MHC H2-K(b). Subcutaneous implantation of B16F10 cells into C57BL/6J mice resulted in high tumorigenicity. The volume of tumors derived from B16F10 cells expressing allogenic MHC H2-K(d) was decreased significantly (P < 0.01). Suppression of MHC H2-K(d)-expressing tumors in C57BL/6J mice was enhanced by immunization with MHC H2-K(d)-expressing splenocytes (P < 0.01). These results suggest that the safeguard system is capable of suppressing tumor formation by the transplanted cells. PMID- 26670280 TI - Nucleus accumbens deep brain stimulation in a rat model of binge eating. AB - Binge eating (BE) is a difficult-to-treat behavior with high relapse rates, thus complicating several disorders including obesity. In this study, we tested the effects of high-frequency deep brain stimulation (DBS) in a rodent model of BE. We hypothesized that BE rats receiving high-frequency DBS in the nucleus accumbens (NAc) core would have reduced binge sizes compared with sham stimulation in both a 'chronic BE' model as well as in a 'relapse to chronic BE' model. Male Sprague-Dawley rats (N=18) were implanted with stimulating electrodes in bilateral NAc core, and they received either active stimulation (N=12) or sham stimulation (N=6) for the initial chronic BE experiments. After testing in the chronic BE state, rats did not engage in binge sessions for 1 month, and then resumed binge sessions (relapse to chronic BE) with active or sham stimulation (N=5-7 per group). A significant effect of intervention group was observed on binge size in the chronic BE state, but no significant difference between intervention groups was observed in the relapse to chronic BE experiments. This research, making use of both a chronic BE model as well as a relapse to chronic BE model, provides data supporting the hypothesis that DBS of the NAc core can decrease BE. Further research will be needed to learn how to increase the effect size and decrease deep brain stimulation-treatment outcome variability across the continuum of BE behavior. PMID- 26670281 TI - Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice. AB - Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3 week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. PMID- 26670282 TI - DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases. AB - The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species. PMID- 26670283 TI - Associations between the schizophrenia susceptibility gene ZNF804A and clinical outcomes in psychosis. AB - We sought to test the hypothesis that the rs1344706 A allele will be associated with worse clinical outcome in first-episode psychosis. A data linkage was set up between a large systematic study of first-episode psychosis and an electronic health-record case register at the South London and Maudsley NHS Foundation Trust -a large provider of secondary mental-health care. A sample of 291 patients, who presented with a first psychotic episode (ICD10 diagnoses F20-29 or F30-33) and in whom the rs1344706 genotype had been assayed, were followed to examine the duration of mental-health in-patient care during the 2 years following first service contact, as a primary outcome. Secondary outcome measures were whether or not an in-patient episode occurred and the number of in-patient episodes during this period. A strong association was found between the number of rs1344706 A alleles and the cumulative duration of mental-health in-patient stay over the 2 years since initial presentation. In the 84.2% who experienced an in-patient episode during this period, the mean duration of admission was an additional 38 days for each A allele increment. Therefore, in addition to its potential role as a risk factor for psychosis, the ZNF804A rs1344706 A allele is associated with worse clinical outcome. PMID- 26670284 TI - An improved human anxiety process biomarker: characterization of frequency band, personality and pharmacology. AB - Anxiety disorders are among the most common mental illness in the western world with a major impact on disability. But their diagnosis has lacked objective biomarkers. We previously demonstrated a human anxiety process biomarker, goal conflict-specific electroencephalography (EEG) rhythmicity (GCSR) in the stop signal task (SST). Here we have developed and characterized an improved test appropriate for clinical group testing. We modified the SST to produce balanced numbers of trials in clearly separated stop-signal delay groups. As previously, right frontal (F8) GCSR was extracted as the difference in EEG log Fourier power between matching stop and go trials (that is, stop-signal-specific power) of a quadratic contrast of the three delay values (that is, power when stopping and going are in balanced conflict compared with the average of when stopping or going is greater). Separate experiments assessed drug sensitivity (n=34) and personality relations (n=59). GCSR in this new SST was reduced by three chemically distinct anxiolytic drugs (administered double-blind): buspirone (10 mg), triazolam (0.25 mg) and pregabalin (75 mg); had a frequency range (4-12 Hz) consistent with rodent model data; and positively correlated significantly with neuroticism and nonsignificantly with trait anxiety scores. GCSR, measured in our new form of the SST, should be suitable as a biomarker for one specific anxiety process in the testing of clinical groups and novel drugs and in the development of measures suitable for individual diagnosis. PMID- 26670286 TI - Anticoagulation-related nephropathy. AB - Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment. PMID- 26670285 TI - Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder. AB - Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma. PMID- 26670287 TI - Cost Drivers After Surgical Management of Proximal Humerus Fractures in Medicare Patients. AB - OBJECTIVES: This comparative effectiveness study sought to determine the impact of complications, readmission, and procedure choice on in-hospital and total 90 day costs for surgical management of proximal humerus fractures. METHODS: Medicare claims data from the Upstate New York area (2008-2009) were evaluated. The study included all patients treated with open reduction and internal fixation (ORIF) or hemiarthroplasty for proximal humerus fracture identified by ICD-9 codes. The primary end points included in-hospital costs and total health care costs within 90 days after the index operation. Multivariable generalized linear models with negative binomial distributions and log link function were used for cost analysis. RESULTS: ORIF was performed in 52 cases and hemiarthroplasty in 57 cases, total n = 109. On univariate analysis, readmission increased in-hospital cost by $54,345 and total 90-day costs by $63,104, whereas complications increased in-hospital cost by $23,300 and total 90-day costs by $30,237. On multivariable analysis, ORIF was associated with 29% lower in-hospital cost compared with hemiarthroplasty [Odds Ratio 0.71; 95% Confidence Interval (CI), 0.54-0.92; P = 0.01], and readmission was associated with a 5.68-fold in-hospital cost increase (Odds Ratio 5.68; CI, 3.57-9.03; P < 0.0001). CONCLUSIONS: Complications and hospital readmission continue to drive cost upward underscoring the need for best practice. The acute inpatient period costs may be decreased with ORIF in appropriately selected patients with proximal humerus fractures in comparison with hemiarthroplasty. This study provides real world cost estimates with the cost implications of complications, readmissions, and procedure choice. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26670288 TI - Prognostic Impact of Postoperative Complications in 502 Patients With Surgically Resected Esophageal Squamous Cell Carcinoma: A Retrospective Single-institution Study. AB - OBJECTIVE: To investigate the relationship between postoperative complications and long-term survival in patients with surgically resected esophageal squamous cell carcinoma (ESCC). SUMMARY BACKGROUND DATA: Esophagectomy is the mainstay of curative treatment for ESCC; however, this complex procedure has high risks of postoperative morbidity and mortality. The impact of postoperative complications on long-term survival of such patients remains controversial. METHODS: This retrospective single institution study included 502 consecutive patients who had undergone resection of ESCC. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. RESULTS: Postoperative complications (>=Clavien-Dindo classification grade 2) occurred in 217 patients (43%). Overall, postoperative complications did not affect long-term clinical outcomes of these patients. However, patients with pulmonary complications had worse overall survival than those without pulmonary complications [log rank P = 0.0002; univariate HR = 1.51, 95% confidence interval (CI) 1.20-1.88, P = 0.0006; multivariate HR = 1.60, 95% CI 1.05-2.38, P = 0.029]. The effect of pulmonary complications was not significantly modified by clinical or pathological features (P for all assessed interactions >0.05). In addition, postoperative chylothorax was also associated with poor overall survival (log rank P = 0.0021), whereas surgical site infection, recurrent nerve paralysis, cardiovascular complication, and anastomotic leakage were not. CONCLUSIONS: Postoperative pulmonary complications may be an independent predictor of poorer long-term survival in patients undergoing resection of ESCCs. PMID- 26670290 TI - A triple carboxylic acid-functionalized RAFT agent platform for the elaboration of well-defined telechelic 3-arm star PDMAc. AB - This communication describes the synthesis of a triple acid-functionalized RAFT agent and its use to prepare well-defined 3-arm star polymers of N,N dimethylacrylamide (DMAc). A simple esterification reaction allowed the convenient integration of three electron-rich naphthalene recognition units on the RAFT agent platform and subsequently the elaboration of a naphthalene end decorated telechelic 3-arm star PDMAc. This functionalized star polymer was further exploited to build a hydrogel with a complementary homoditopic host unit featuring tetracationic macrocycle cyclobis(paraquat-p-phenylene) units. PMID- 26670289 TI - Biotechnological production of 1,2,4-butanetriol: An efficient process to synthesize energetic material precursor from renewable biomass. AB - 1,2,4-Butanetriol (BT) is a valuable chemical with extensive applications in many different fields. The traditional chemical routes to synthesize BT suffer from many drawbacks, e.g., harsh reaction conditions, multiple steps and poor selectivity, limiting its industrial production. In this study, an engineered Escherichia coli strain was constructed to produce BT from xylose, which is a major component of the lignocellulosic biomass. Through the coexpression of a xylose dehydrogenase (CCxylB) and a xylonolactonase (xylC) from Caulobacter crescentus, native E. coli xylonate dehydratase (yjhG), a 2-keto acid decarboxylase from Pseudomonas putida (mdlC) and native E. coli aldehyde reductase (adhP) in E. coli BL21 star(DE3), the recombinant strain could efficiently convert xylose to BT. Furthermore, the competitive pathway responsible for xylose metabolism in E. coli was blocked by disrupting two genes (xylA and EcxylB) encoding xylose isomerase and xyloluse kinase. Under fed-batch conditions, the engineered strain BL21DeltaxylAB/pE-mdlCxylBC&pA-adhPyjhG produced up to 3.92 g/L of BT from 20 g/L of xylose, corresponding to a molar yield of 27.7%. These results suggest that the engineered E. coli has a promising prospect for the large-scale production of BT. PMID- 26670291 TI - Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice. AB - Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of alpha-tocopherol and beta-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the role of Angiotensin II on hepatic damage and if alpha-tocopherol and beta carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe(-/-)mice by infusion of Angiotensin II followed by oral administration with alpha-tocopherol and beta-carotene-enriched diet for 60 days. Investigations showed fibrosis, kupffer cell hyperplasia, hepatocyte degeneration and hepatic cell apoptosis; sinusoidal dilatation along with haemorrhages; evidence of fluid accumulation; increased ROS level and increased AST and ALT activities. In addition, tPA and uPA were down-regulated due to 42-fold up-regulation of PAI-1. MMP-2, MMP-9, MMP-12, and M-CSF were down-regulated in Angiotensin II-treated animals. Notably, alpha-tocopherol and beta-carotene treatment controlled ROS, fibrosis, hepatocyte degeneration, kupffer cell hyperplasia, hepatocyte apoptosis, sinusoidal dilatation and fluid accumulation in the liver sinusoids, and liver enzyme levels. In addition, PAI-1, tPA and uPA expressions were markedly controlled by beta-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that alpha-tocopherol and beta-carotene treatment has salubrious role in repairing hepatic pathology. PMID- 26670292 TI - Evaluating the potential impact of proton carriers on syntrophic propionate oxidation. AB - Anaerobic propionic acid degradation relies on interspecies electron transfer (IET) between propionate oxidisers and electron acceptor microorganisms, via either molecular hydrogen, formate or direct transfers. We evaluated the possibility of stimulating direct IET, hence enhancing propionate oxidation, by increasing availability of proton carriers to decrease solution resistance and reduce pH gradients. Phosphate was used as a proton carrying anion, and chloride as control ion together with potassium as counter ion. Propionic acid consumption in anaerobic granules was assessed in a square factorial design with ratios (1:0, 2:1, 1:1, 1:2 and 0:1) of total phosphate (TP) to Cl(-), at 1X, 10X, and 30X native conductivity (1.5 mS.cm(-1)). Maximum specific uptake rate, half saturation, and time delay were estimated using model-based analysis. Community profiles were analysed by fluorescent in situ hybridisation and 16S rRNA gene pyrosequencing. The strongest performance was at balanced (1:1) ratios at 10X conductivity where presumptive propionate oxidisers namely Syntrophobacter and Candidatus Cloacamonas were more abundant. There was a shift from Methanobacteriales at high phosphate, to Methanosaeta at low TP:Cl ratios and low conductivity. A lack of response to TP, and low percentage of presumptive electroactive organisms suggested that DIET was not favoured under the current experimental conditions. PMID- 26670293 TI - Stroke. Bilingualism is associated with better cognitive outcomes after stroke. PMID- 26670294 TI - Epilepsy. Early treatment could prevent genetic epilepsy in mice. PMID- 26670295 TI - Neuromuscular disease. Diagnosis and discovery in limb-girdle muscular dystrophy. AB - Whole-exome sequencing is a new tool for neuromuscular clinicians, and recent findings show that it improves the diagnosis of limb-girdle muscular dystrophy. The technique has a dual role as a tool for diagnosis and discovery in genetically heterogeneous neuromuscular diseases. PMID- 26670296 TI - Stroke. Support for IV tPA in ischaemic stroke in elderly people. AB - In Europe, use of intravenous tissue plasminogen activator (tPA) in patients older than 80 years is discouraged because these patients have been excluded from certain past clinical trials. A new retrospective, observational study shows that tPA can substantially improve functional outcome after ischaemic stroke in patients aged 80-89 years. PMID- 26670297 TI - Clinical assessment of social cognitive function in neurological disorders. AB - Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice. PMID- 26670298 TI - Controversies in epidemiology of intracranial aneurysms and SAH. AB - Rupture of an intracranial aneurysm is the most common cause of subarachnoid haemorrhage (SAH), which is a life-threatening acute cerebrovascular event that typically affects working-age people. The exact prevalence of unruptured intracranial aneurysms (UIAs) is unknown, but at least one in 20 to 30 adults is likely to carry an asymptomatic UIA. Approximately one quarter of these UIAs rupture in a lifetime. Complex methodological challenges in conducting studies of epidemiology and risk factors for UIAs and SAH might have led to conclusions being drawn on the basis of epidemiological data of variable quality. We believe that, as a result, misconceptions about UIAs and SAH may have arisen. In this Perspectives article, we discuss three possible misconceptions about the epidemiology of UIAs and SAH, and suggest how the quality of future research could be improved. PMID- 26670299 TI - Genetic risk factors for spontaneous intracerebral haemorrhage. AB - Intracerebral haemorrhage (ICH) is associated with the greatest morbidity and mortality of all stroke subtypes. Established risk factors for ICH include hypertension, alcohol use, current cigarette smoking, and use of oral anticoagulants and/or antiplatelet agents. Familial aggregation of ICH has been observed, and the heritability of ICH risk has been estimated at 44%. Few genes have been found to be associated with ICH at the population level, and much of the evidence for genetic risk factors for ICH comes from single studies conducted in relatively small and homogenous populations. In this Review, we summarize the current knowledge of genetic variants associated with primary spontaneous ICH. Two variants of the gene encoding apolipoprotein E (APOE) - which also contributes to the pathogenesis of cerebral amyloid angiopathy - are the most likely candidates for variants that increase the risk of ICH. Other promising candidates for risk alleles in ICH include variants of the genes ACE, PMF1/SLC25A44, COL4A2, and MTHFR. Other genetic variants, related to haemostasis, lipid metabolism, inflammation, and the CNS microenvironment, have been linked to ICH in single candidate gene studies. Although evidence for genetic contributions to the risk of ICH exists, we do not yet fully understand how and to what extent this information can be utilized to prevent and treat ICH. PMID- 26670301 TI - [Secondary Splenic Rupture after Initially Inconspicuous CAT Scan]. AB - BACKGROUND: Splenic injuries occur in 1-5 % of blunt abdominal trauma cases. After initial haemorrhagic compression, secondary delayed spleen rupture can occur with a latency of one day to a month or longer. Mortality is then up to 15 %. The spleen injury is almost always recognisable on CT or ultrasound. CASE HISTORY: In one case from our clinic, secondary splenic rupture occurred in a patient after discharge from hospitalisation, even though the initial CT and ultrasound were unremarkable. The patient survived, and underwent emergent splenectomy 8 days after the trauma. An expert review of the case identified no errors in treatment. CONCLUSION: No case of secondary splenic rupture after initially unremarkable diagnostic studies and clinical course has previously been published. Secondary splenic rupture has a high mortality rate. Patients should be advised of potential complications after hospital discharge, and should return to the hospital immediately in case of symptoms. PMID- 26670300 TI - Study protocol of "CHAPS": a randomized controlled trial protocol of Care Coordination for Health Promotion and Activities in Parkinson's Disease to improve the quality of care for individuals with Parkinson's disease. AB - BACKGROUND: Parkinson's disease, the second most common neurodegenerative disease, is diagnostically defined by motor impairments, but also includes often under-recognized impairments in cognition, mood, sleep, and the autonomic nervous system. These problems can severely affect individuals' quality of life. In our prior research, we have developed indicators to measure the quality of care delivered to patients with Parkinson's disease, and we identified gaps in delivering evidence-based treatments for this population. Effective strategies to close these gaps are needed to improve patient quality of life. METHODS/DESIGN: Building on prior research we developed a multi-faceted proactive implementation program called Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS). To be eligible, patients had to have at least two visits with a primary diagnosis of idiopathic Parkinson's disease (ICD-9 code: 332.0) at one of five Veterans Affairs Medical Centers in the southwestern United States from 2010 to 2014. The program consists of telephone assessments, evidence based protocols, and tools to enhance patient self-management, care planning, and coordination of care across providers, including an electronic database to support and track coordination of care. Our mixed-methods study employs a randomized, controlled trial design to test whether the CHAPS intervention improves performance in 38 quality measures among an analytic sample of 346 patients. The 38 quality measures are categorized into overarching areas of communication, education, and continuity; regulatory reporting; diagnosis; periodic assessment; medication use; management of motor and non-motor symptoms; use of non-pharmacological approaches and therapies; palliative care; and health maintenance. Secondary outcomes are patient health-related quality of life, self efficacy, and perceptions of care quality. We are also evaluating the extent of the CHAPS Program implementation and measuring program costs and impacts on health services utilization, in order to perform a analysis of the CHAPS program from the perspective of the Veterans Health Administration (VA). Outcomes are assessed by interviewer-administered surveys collected at baseline and at 6, 12, and 18 months, and by medical record chart abstractions. Analyses will be intention-to-treat. DISCUSSION: The CHAPS Program is poised for dissemination within the VA National Parkinson's Disease Research, Education, and Clinical Center Consortium if demonstrated efficacious. TRIAL REGISTRATION: ClinicalTrials.gov NCT01532986; registered on January 13, 2012. PMID- 26670302 TI - [Elastic Stable Intramedullary Nailing (ESIN) of Metatarsal Fractures]. AB - AIM: In the treatment of metatarsal fractures, the objective is early restoration of the physiological painless function of the foot. While undisplaced metatarsal fractures can be treated non-surgically, displaced fractures are a valid indication for reduction and internal fixation. Whereas plate fixation may lead to soft tissue irritation involving tendon adhesions and scar formation, retrograde percutaneous pinning may harm the intact metatarsophalangeal joint and lead to joint stiffness. We have therefore used the technique of elastic stable intramedullary nailing (ESIN) with titanium elastic nails (TEN) to achieve minimally invasive, antegrade splinting of short metatarsal shaft and neck fractures. METHOD: Within 7 years, ESIN was performed in 22 patients. The surgical technique is presented and the functional results and complications were retrospectively evaluated using the AOFAS Midfoot Score. RESULTS: Nineteen patients were analysed after an average follow-up of 25.6 +/- 21.3 months (range: 3-72 months). The mean AOFAS score was 93.9 +/- 10.4 (range 62-100) points. One case of skin irritation required TEN shortening. Pseudarthrosis, secondary fracture dislocation and nail breakage were not observed. After TEN removal 13.4 +/- 12.9 (range: 5-52) weeks after implantation, no refracture occurred. CONCLUSION: Antegrade, minimally invasive, elastic stable intramedullary nailing of short metatarsal shaft and neck fractures using titanium nails (TEN) is a safe surgical procedure and achieves primary functional stability. It reliably leads to fracture healing and produces good functional results. PMID- 26670303 TI - [Sagittal Balance of the Spine--Clinical Importance and Radiographic Assessment]. AB - Sagittal deformities of the spine frequently result in back pain, as patients have to expend much energy in compensation. The sagittal alignment of the spine is defined by its curvatures (lordosis and kyphosis) relative to the position of the pelvis. Diagnostic assessment is based on full spine a. p. and lateral X rays. The sagittal balance is primarily described by different angles that can be measured, e.g. lumbar lordosis, pelvic incidence, pelvic tilt and thoracic kyphosis. The quality of life can best be estimated by subtracting lumbar lordosis from the pelvic incidence. However, initial evaluation of the sagittal balance can also be based on the sagittal vertical axis. The severity of imbalance can be described by the sagittal vertical axis and the pelvic tilt, but surgical therapy necessitates a more profound analysis, which can be based on the SRS-Schwab classification. PMID- 26670304 TI - Erratum. AB - In the article by Kim et al., entitled "The sound of a Buk (Korean traditional drum) attenuates anaphylactic reactions by the activation of estrogen receptor beta" [Int Arch Allergy Immunol 2015;167:242-49, DOI: 10.1159/000439567], there is an error in Materials and Methods. The sample size of animals was larger than 15, therefore the third paragraph should read: Compound 48/80-Induced Systemic Anaphylaxis. Mice were given an intraperitoneal injection of compound 48/80 (6.5 mg/kg). The period used to observe mortality was based on the results of a pretest during which mice died within 30 min of administration. Ketotifen was used as a positive control (1 MUg/kg, p.o.). Mortality was monitored for 40 min after injection. Mice were allocated to each group and divided into 5 groups: (1) no treatment, (2) compound 48/80 injection, (3) compound 48/80 injection and treatment with ketotifen, (4) compound 48/80 injection and exposure to Buk music, and (5) compound 48/80 injection and exposure to white noise. Three independent experiments were performed. PMID- 26670305 TI - Predicted optimum ambient temperatures for broiler chickens to dissipate metabolic heat do not affect performance or improve breast muscle quality. AB - An experiment was conducted to test the hypothesis that muscle damage in fast growing broiler chickens is associated with an ambient temperature that does not permit the birds to lose metabolic heat resulting in physiological heat stress and a reduction in meat quality. The experiment was performed in 4 climate chambers and was repeated in 2 trials using a total of 200 male broiler chickens. Two treatments compared the recommended temperature profile and a cool regimen. The cool regimen was defined by a theoretical model that determined the environmental temperature that would enable heat generated by the bird to be lost to the environment. There were no differences in growth rate or feed intake between the two treatments. Breast muscles from birds on the recommended temperature regimen were lighter, less red and more yellow than those from the cool temperature regimen. There were no differences in moisture loss or shear strength but stiffness was greater in breast muscle from birds housed in the cool compared to the recommended regimen. Histopathological changes in the breast muscle were similar in both treatments and were characterised by mild to severe myofibre degeneration and necrosis with regeneration, fibrosis and adipocyte infiltration. There was no difference in plasma creatine kinase activity, a measure of muscle cell damage, between the two treatments consistent with the absence of differences in muscle pathology. It was concluded that breast muscle damage in fast-growing broiler chickens was not the result of an inability to lose metabolic heat at recommended ambient temperatures. The results suggest that muscle cell damage and breast meat quality concerns in modern broiler chickens are related to genetic selection for muscle yields and that genetic selection to address breast muscle integrity in a balanced breeding programme is imperative. PMID- 26670306 TI - Usefulness of two interferon-gamma release assays for rheumatic disease. AB - BACKGROUND: The aim of this study was to evaluate the performance of two interferon-gamma release assays (IGRA), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for pediatric patients with rheumatic disease in Japan and to analyze the frequencies of indeterminate test results with these kits. METHODS: An IGRA was performed in 108 patients <20 years old in order to exclude tuberculosis infection at the time of first application of or change of biological agents and immunosuppressants in Yokohama City University Hospital. RESULTS: None of the 108 patients tested had active tuberculosis during the 50 month observation period. Indeterminate results of QFT-GIT and T-SPOT.TB tests were obtained in 9.9% and in 0% of cases, respectively. Indeterminate results were obtained significantly more frequently in patients on prednisolone >0.5 mg/kg and in patients with active underlying disease. Use of biologicals and other immunosuppressants had no effect on these measurements. CONCLUSIONS: IGRA are very useful for excluding tuberculosis infection in patients with rheumatic disease before starting new immunosuppressant therapy. Furthermore, the T-SPOT.TB test was suitable for evaluating latent tuberculosis infection even under immunosuppression, when TB tests are generally hard to perform. PMID- 26670307 TI - Long-Term Evaluation of Colestilan in Chronic Kidney Disease Stage 5 Dialysis Patients with Hyperphosphataemia. AB - BACKGROUND: This study investigated in a North American patient population the longer-term treatment effects of the phosphate binder, colestilan, in patients with CKD Stage 5D and hyperphosphataemia. METHODS: One hundred and sixteen CKD Stage 5D patients with hyperphosphataemia were entered into a multi-centre, open label study where they received flexible dose colestilan (6-15 g/day) to maintain serum phosphorus levels between 3.5 and 5.5 mg/dl. The primary endpoint was safety, assessed by treatment-emergent adverse events. Efficacy was assessed by changes in serum phosphorus, mineral metabolism, lipids, HbA1c, uric acid and bone markers. RESULTS: Serum phosphorus was significantly reduced by 1.18 mg/dl (p < 0.001), from 6.99 mg/dl at baseline to 5.80 mg/dl at week 52. LDL cholesterol was also significantly reduced as well as uric acid. Significant change was observed only for one bone marker - PINP. Most adverse events were of mild or moderate intensity. Nausea (22.4%), vomiting (21.6%), and diarrhoea (19.8%) were most commonly reported. CONCLUSIONS: Long-term flexible dosing with colestilan reduces serum phosphorus and demonstrates an acceptable safety and tolerability profile. PMID- 26670308 TI - Responding to Change: Introducing the New Business and Practice Improvement Section. PMID- 26670309 TI - Pulmonary artery ablation to treat pulmonary arterial hypertension: a case report. AB - INTRODUCTION: Idiopathic pulmonary arterial hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance that results in right heart failure and premature death. Although therapies exist to improve hemodynamic instability and symptoms, there is no cure for pulmonary arterial hypertension and it remains a life-threatening condition. A recent study performed in China reported, for the first time, the effect of pulmonary arterial denervation on functional capacity and hemodynamics in patients with refractory idiopathic pulmonary arterial hypertension. CASE PRESENTATION: We report a case of a 60-year-old white Brazilian man, with controlled hypertension and stage 2 obesity who complained of progressive fatigue with moderate to light exertion of approximately 1 year's duration. During this period, he underwent myocardial perfusion scintigraphy without evidence of obstructive ischemic disease. He had no clinical evidence of systolic heart failure. He had undergone biological mitral valve replacement 3 years previously for mitral valve stenosis and ablation of atrioventricular nodal reentry tachycardia 18 months previously. At the time of valve replacement, he had no reported evidence of pulmonary arterial hypertension. His echocardiogram showed normal function of a mitral prosthesis, normal global left ventricular systolic function (left ventricular ejection fraction 62 % measured using the Teichholz method), stage I diastolic dysfunction, and a mean systolic pulmonary arterial blood pressure of 50 mmHg. In the 6-minute walk test, the patient walked 104 meters. Catheterization of his right heart chambers and pulmonary arteries confirmed the diagnosis of pulmonary hypertension. Electroanatomic reconstruction of the right ventricular outflow tract and pulmonary artery was performed under direct fluoroscopic visualization, and a merger was made with a formatted image of cardiac computed tomography angiography. Then we performed irrigated cardiac catheter ablation of the pulmonary trunk. CONCLUSIONS: At the patient's 3-month follow-up, he showed improvement in functional class for fatigue on major exertion, increased distance walked in the 6-minute walk test, and reductions in pressure of both the right cavities and the pulmonary artery. Currently, with 6 months of clinical follow up, the patient has maintained his functional classification and is pedaling his bicycle. PMID- 26670310 TI - Crystalloid podocytopathy with focal segmental glomerulosclerosis in PCM: a case report. AB - BACKGROUND: Crystalloid podocytopathy with focal segmental glomerulosclerosis in plasma cell myeloma (PCM) is rare. CASE PRESENTATION: We present a case of crystalline deposition in the bone marrow (BM) and various renal cells with only proteinuria as a symptom. As workup for proteinuria, a renal biopsy sample was obtained. EM showed multiple crystalline depositions in renal tubular cells and podocytes. Focal segmental glomerulosclerosis with crystalloid podocytopathy was diagnosed. Because monoclonal gammopathy was detected in the serum and urine, a BM study was also performed. Plasma cells with needle-shaped inclusion bodies were observed. The crystalline deposits in the plasma cells and podocytes were positive for Masson's trichrome and kappa light-chain staining. These findings indicated that the crystalline deposits originated from paraprotein. The case showed a rare process of focal segmental glomerulosclerosis via crystalline deposition in podocytes in plasma cell myeloma. CONCLUSIONS: Crystalloid podocytopathy is a likely cause of renal damage such as FSGS in PCM, although it is an uncommon mechanism for myeloma kidney. PMID- 26670311 TI - Toward earlier identification and preventative intervention in schizophrenia: evidence from the London Child Health and Development Study. AB - PURPOSE: The London Child Health and Development Study (CHADS) is a prospective, longitudinal investigation of children, sampled from the general community aged 9 11 years and assessed biennially, who present premorbid risk markers for schizophrenia. The study aims to characterise developmental trajectories of psychological, cognitive, and biological functioning in at-risk children and identify potential targets for early preventative intervention. This review summarises CHADS findings, discusses these in the context of recent theory regarding aetiology and prevention of schizophrenia, and highlights challenges to be addressed with future research. METHODS: We review (1) epidemiological information on the prevalence and correlates of developmental antecedents of schizophrenia in the general child population, (2) evidence of psychosocial, cognitive, and biological dysfunctions in at-risk children presenting multiple antecedents of schizophrenia and at-risk children with a family history of schizophrenia, and (3) related findings from an associated sample of help-seeking children receiving intervention. RESULTS: Community-based screening of 9-11-year olds identified ~9 % with a triad of antecedents of schizophrenia [including psychotic-like experiences (PLEs)] who are putatively at-risk of psychosis; these children reported greater exposure and responsivity to stressors, impairments in general intelligence and specific cognitive functions, brain structure and function abnormalities, and neuromotor dysfunction. Preliminary evidence suggests distressing PLEs are a viable target for cognitive-behavioural intervention in at risk children. CONCLUSIONS: Intervention in early, premorbid phases of illness might alleviate current difficulties and avert future schizophrenia using benign treatments. The CHADS programme has identified several markers that may index early pathophysiology and constitute potential targets for preventative intervention. PMID- 26670312 TI - The potential role of Punica granatum treatment on murine malaria-induced hepatic injury and oxidative stress. AB - Malaria is a health burden disease where the world harnessed the power of expertise and innovation to understand the biology of the parasite and the pathogenesis of the disease as well as to discover effective drugs. However, the treatment of malaria remains a challenging task and inadequate to address today's perplexing problem, the emergence of resistant strains. Historically, traditional medicine has been a mainstay for remediation and still retains its importance with the presence of potent natural products. Pomegranate has been used as antioxidant and anti-inflammatory against a range of diseases. Therefore, pomegranate peel extract (PPE) was used in this study to examine its effect on Plasmodium chabaudi-induced hepatic inflammation. Animals were allocated into three groups: a vehicle control group, a group infected with 10(6) P. chabaudi parasitized erythrocytes and a pomegranate-treated group infected with 10(6) P. chabaudi-parasitized erythrocytes. This group received 100 MUl of 300 mg/kg PPE after infection. The results showed the effectiveness of PPE on reversing the anaemic signs that have been provoked by P. chabaudi infection through instating the haemoglobin concentration and erythrocyte count back to normal values. Moreover, PPE exhibited hepatoprotective activities upon histopathological examination and liver function tests. These data were further confirmed by the significant reduction of the hepatic oxidative markers, glutathione, nitric oxide and malondialdehyde, in mice infected with P. chabaudi. Based on these outcomes, pomegranate could be used as a hepatoprotective agent against P. chabaudi-induced hepatic injury. However, further studies are needed in order to determine the mode of action of pomegranate upon infection. PMID- 26670313 TI - Molecular detection of six (endo-) symbiotic bacteria in Belgian mosquitoes: first step towards the selection of appropriate paratransgenesis candidates. AB - Actually, the use of symbiotic bacteria is one of alternative solution to avoid vector resistance to pesticides. In Belgium, among 31 identified mosquito species, 10 were considered as potential vectors. Given to introduction risks of arbovirosis, the purpose of this study was to investigate the presence of symbiosis bacteria in potential mosquito vectors. Eleven species caught from 12 sites in Belgium were used: Culex pipiens s.l., Culex torrentium, Culex hortensis, Anopheles claviger, Anopheles maculipennis s.l., Anopheles plumbeus, Culiseta annulata, Ochlerotatus geniculatus, Ochlerotatus dorsalis, Aedes albopictus, and Coquillettidia richiardii. Six genera of symbiotic bacteria were screened: Wolbachia sp., Comamonas sp, Delftia sp., Pseudomonas sp., Acinetobacter sp., and Asaia sp. A total of 173 mosquito individuals (144 larvae and 29 adults) were used for the polymerase chain reaction screening. Wolbachia was not found in any Anopheles species nor Cx. torrentium. A total absence of Comamonas and Delftia was observed in all species. Acinetobacter, Pseudomonas, and Asaia were found in most of species with a high prevalence for Pseudomonas. These results were discussed to develop potential strategy and exploit the variable occurrence of symbiotic bacteria to focus on them to propose biological ways of mosquito control. PMID- 26670314 TI - The vector tick Ixodes ricinus feeding on an arboreal rodent-the edible dormouse Glis glis. AB - The reservoir competence and long life expectancy of edible dormice, Glis glis, suggest that they serve as efficient reservoir hosts for Lyme disease (LD) spirochetes. Their arboreality, however, may reduce the probability to encounter sufficient questing Ixodes ricinus ticks to acquire and perpetuate LD spirochetes. To define the potential role of this small arboreal hibernator in the transmission cycle of LD spirochetes, we examined their rate and density of infestation with subadult ticks throughout the season of activity. Of the 1081 edible dormice that we captured at five study sites in Southern Germany and inspected for ticks at 2946 capture occasions, 26 % were infested with at least one and as many as 26 subadult ticks on their ear pinnae. The distribution of ticks feeding on edible dormice was highly aggregated. Although only few individuals harbored nymphal ticks soon after their emergence from hibernation, the rate of nymphal infestation increased steadily throughout the season and reached about 35 % in September. Dormice inhabiting a site with few conspecifics seemed more likely to be infested by numerous ticks, particularly nymphs, than those individuals living in densely populated sites. Male dormice were more likely to be parasitized by numerous nymphs than were females, independent of their age and body mass. Our observation that season, population density, and sex affect the rates of ticks feeding on edible dormice suggests that the contribution of edible dormice to the transmission cycle of LD spirochetes depends mainly on their ranging behavior and level of activity. PMID- 26670315 TI - Phylogenetic Networks with Every Embedded Phylogenetic Tree a Base Tree. AB - We show that the class of tree-child networks is precisely the class of tree based networks with the property that every embedded phylogenetic tree is a base tree. PMID- 26670316 TI - Protein Synthesis Driven by Dynamical Stochastic Transcription. AB - In this manuscript, we propose a mathematical framework to couple transcription and translation in which mRNA production is described by a set of master equations, while the dynamics of protein density is governed by a random differential equation. The coupling between the two processes is given by a stochastic perturbation whose statistics satisfies the master equations. In this approach, from the knowledge of the analytical time-dependent distribution of mRNA number, we are able to calculate the dynamics of the probability density of the protein population. PMID- 26670317 TI - Efficacy of "Awake ECMO" for critical respiratory failure after pediatric open heart surgery. AB - A 4-year-old boy with atrioventricular discordance, double-outlet right ventricle, pulmonary stenosis, and mitral regurgitation, was undergoing anatomical repair consisting of Senning, Rastelli, Damus-Kaye-Stansel procedures, and a mitral valve repair, complained of post-operative excessive airway tract secretion, which ultimately developed into acute respiratory distress syndrome (ARDS) 28 days after the operation. The cause of the ARDS was thought to be frequent manual positive pressure recruitment and prolonged inhalation of pure oxygen. At 45 days after the operation, hypercapnia and respiratory acidosis turned out to be irreversible, and therefore, veno-arterial extracorporeal membrane oxygenation (ECMO) was established utilizing the Endumo((r))4000 system. Pulmonic interstitial inflammation gradually improved while resting the lung under ECMO support; however, effective ventilation volume decreased critically because a massive pulmonary hemorrhage occurred at 2 and 9 days after the initiation of ECMO. To maximize the effectiveness of respiratory physical therapy, "Awake ECMO" was started and tidal volume dramatically increased with a regained cough reflex. Five days later, he was successfully weaned off from ECMO, and discharged 7 months after the operation without any neurological and physiological sequelae. PMID- 26670318 TI - Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long term outcomes and risk factors for hypervascular transformation. AB - PURPOSE: To evaluate the long-term outcomes and imaging features associated with hypervascularization of hypovascular nodules that show T2 iso-/hypointensity and hypointensity on hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) images in patients with chronic liver disease. MATERIALS AND METHODS: Sixty patients and 114 nodules, which were hypovascular and iso /hypointense on T2-weighted images and hypointense on HBP of gadoxetic acid enhanced MRI, were included. We evaluated the effect of baseline clinical features, baseline MR features and growth rate on subsequent hypervascularization. RESULTS: Twenty-seven nodules in 21 patients transformed to hypervascular hepatocellular carcinoma (HCC). Using multivariate Cox analysis, T1 hyperintensity (hazard ratio [HR] = 2.69, P = 0.021), previous history of HCC (HR = 2.64, P = 0.021), and initial nodule size (HR = 1.09, P = 0.046) were identified to be associated with hypervascularization. The growth rate of nodules was a more powerful determinant of subsequent hypervascularization than baseline clinical and MR features. At long-term follow-up after >3 years, only one nodule with T1 isointensity showed hypervascularization. CONCLUSION: Careful follow-up or diagnostic procedures, such as biopsy, should be considered for up to 3 years after detection of hypointense nodules on HBP with T1 hyperintensity or a higher growth rate. KEY POINTS: * T1 hyperintensity is a baseline MR predictive factor for subsequent hypervascularization. * A higher growth rate is a more powerful determinant of subsequent hypervascularization. * Management of patients with these predictive factors requires more attention. PMID- 26670319 TI - Diffusion measurement of intraplaque hemorrhage and intramural hematoma using diffusion weighted MRI at 3T in cervical artery. AB - OBJECTIVES: To assess the difference between carotid haemorrhagic plaque and non haemorrhagic plaque by using diffusion-weighted imaging (DWI) and to evaluate carotid intraplaque haemorrhage (IPH) and intramural hematoma (IMH) of cervical artery dissection with apparent diffusion coefficient (ADC) measurement. METHODS: Fifty-one symptomatic patients underwent 3.0-T carotid MR imaging, including conventional sequences, three-dimensional (3D) magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequence, and DWI. Thirty-nine patients with carotid plaque and eight patients with IMH of cervical artery dissection were finally included. The groups of hemorrhagic plaque, non-hemorrhagic plaque and IMH were divided according to 3D MPRAGE sequence. ADC values of different groups were measured, and t tests were performed. RESULTS: The mean ADC values of hemorrhagic plaques, non-hemorrhagic plaque and IMH were (1.284 +/- 0.327) * 10( 3)mm(2)/s, (1.766 +/- 0.477) * 10(-3)mm(2)/s, and (0.563 +/- 0.119) * 10( 3)mm(2)/s, respectively. The mean ADC values of hemorrhagic and non-hemorrhagic regions in the hemorrhagic plaque group were (0.985 +/- 0.376) * 10(-3)mm(2)/s and (1.480 +/- 0.465) * 10(-3)mm(2)/s, respectively. The differences between the hemorrhagic plaque and non-hemorrhagic plaque, hemorrhagic region and non hemorrhagic region in hemorrhagic plaque, and the hemorrhagic region in the hemorrhagic plaque and IMH of artery dissection were significant (P < 0.05). CONCLUSION: DWI may be a useful complement to conventional MR imaging for identifying haemorrhage of carotid plaques and differentiate IMHs from IPH. KEY POINTS: * ADC values of IPH are lower than the plaque without IPH. * DWI might be a useful complement to identify IPH. * IMH may be differentiated from IPH by using DWI. PMID- 26670320 TI - The role of Size-Specific Dose Estimate (SSDE) in patient-specific organ dose and cancer risk estimation in paediatric chest and abdominopelvic CT examinations. AB - OBJECTIVES: To develop a clinically applicable method to estimate patient specific organ and blood doses and lifetime attributable risks (LAR) from paediatric torso CT examinations. METHODS: Individualized voxel models were created from full-body CT data of 10 paediatric patients (2-18 years). Patient specific dose distributions of chest and abdominopelvic CT scans were simulated using Monte Carlo methods. Blood dose was calculated as a weighted sum of simulated organ doses. LAR of cancer incidence and mortality were estimated, according to BEIR-VII. A second simulation and blood dose calculation was performed using only the thoracic and abdominopelvic region of the original voxel models. For each simulation, the size-specific dose estimate (SSDE) was calculated. RESULTS: SSDE showed a significant strong linear correlation with organ dose (r > 0.8) and blood dose (r > 0.9) and LAR (r > 0.9). No significant differences were found between blood dose calculations with the full-body voxel models and the thoracic or abdominopelvic models. CONCLUSION: Even though clinical CT images mostly do not cover the whole body of the patient, they can be used as a voxel model for blood dose calculation. In addition, SSDE can estimate patient-specific organ and blood doses and LAR in paediatric torso CT examinations. KEY POINTS: * Blood dose can be simulated using the patient's clinical CT images. * SSDE estimates patient-specific organ/blood dose and LAR in paediatric CAP CT-examinations. * SSDE makes on-the-spot dose and LAR estimations possible in routine clinical practice. PMID- 26670321 TI - Early quantitative CT perfusion parameters variation for prediction of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. AB - OBJECTIVES: To prospectively evaluate the predictive value of cerebral perfusion computerized tomography (CTP) parameters variation between day0 and day4 after aneurysmal subarachnoid haemorrhage (aSAH). METHODS: Mean transit time (MTT) and cerebral blood flow (CBF) values were compared between patients with delayed cerebral ischemia (DCI+ group) and patients without DCI (DCI- group) for previously published optimal cutoff values and for variations of MTT (DeltaMTT) and of CBF (DeltaCBF) values between day0 and day4. DCI+ was defined as a cerebral infarction on 3-months follow-up MRI. RESULTS: Among 47 included patients, 10 suffered DCI+. Published optimal cutoff values did not predict DCI, either at day0 or at day4. Conversely, DeltaMTT and DeltaCBF significantly differed between the DCI+ and DCI- groups, with optimal DeltaMTT and DeltaCBF values of 0.91 seconds (83.9 % sensitivity, 79.5 % specificity, AUC 0.84) and 7.6 mL/100 g/min (100 % sensitivity, 71.4 % specificity, AUC 0.86), respectively. In multivariate analysis, DeltaCBF (OR = 1.91, IC95% 1.13-3.23 per each 20 % decrease of DeltaCBF) and DeltaMTT values (OR = 14.70, IC95% 4.85-44.52 per each 20 % increase of DeltaMTT) were independent predictors of DCI. CONCLUSIONS: Assessment of MTT and CBF value variations between day0 and day4 may serve as an early imaging surrogate for prediction of DCI in aSAH. KEY POINTS: * CT perfusion values are an imaging surrogate for prediction of DCI. * Early variations (day0 day4) after aneurysmal subarachnoid haemorrhage predicted DCI. * A CBF decrease of 7.6 mL/min/100 g predicted DCI with 100 % sensitivity. * An MTT increase of 0.91 seconds predicted DCI with 83.9 % sensitivity. * DCI risk multiplied by 2 per 20 % DeltaCBF decrease and by 15 per 20 % DeltaMTT increase. PMID- 26670323 TI - Factor Structure of the Parent-Report Mood and Feelings Questionnaire (MFQ) in an Outpatient Mental Health Sample. AB - The current investigation examined the internal structure and discriminant validity of the parent-report Mood and Feelings Questionnaire (MFQ-P), a commonly used measure of depressive symptoms in youth. A total of 1493 families with youth ages 5 to 18 (61.02 % male) presenting for treatment at an outpatient mental health clinic were randomly allocated to an Exploratory Sample 1 or to a Replication Sample 2. Internal structure of the MFQ-P was examined using exploratory factor analysis in Sample 1 (N = 769) and then replicated using confirmatory factor analysis in Sample 2 (N = 724). Results of the exploratory factor analysis yielded a 5-factor structure comprised of core mood, vegetative, suicidality, cognitive, and agitated distress symptom subscales. The 5-factor solution was replicated in Sample 2 with adequate fit, (CFI = 0.908, TLI = 0.974, RMSEA =0.067). Results lend statistical support for 5 candidate subscales of the MFQ-P. These potential subscales may aid in efficient identification of critical symptoms of depression. PMID- 26670324 TI - Seventeen years of statin pharmacogenetics: a systematic review. AB - AIM: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review. METHODS: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events. RESULTS: In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events. CONCLUSION: Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice. PMID- 26670322 TI - Mechanisms of Antioxidant Induction with High-Dose N-Acetylcysteine in Childhood Cerebral Adrenoleukodystrophy. AB - BACKGROUND: Childhood cerebral adrenoleukodystrophy (CCALD), a progressive demyelinating disease affecting school-aged boys, causes death within a few years. Oxidative stress is an important contributing factor. N-acetylcysteine (NAC; 280 mg/kg/day) added as adjunctive therapy to reduced-intensity hematopoietic cell transplantation (HCT) improves survival in advanced cases. However, the mechanisms underlying the benefits of NAC are unclear. OBJECTIVE: The aim of this study was to understand the mechanism of action of NAC in the setting of HCT in CCALD. METHODS: Immunoassays were carried out to determine changes in heme oxygenase-1 (HO-1) and ferritin expression in plasma samples collected from boys with CCALD at three different timepoints during the course of transplantation. In addition, the induction of HO-1 was also confirmed in normal fibroblasts following incubation with 10-100 umol/L NAC for 4 h. RESULTS: Following NAC therapy we observed an increase in expression of the antioxidants HO-1 (~4-fold) and its effector ferritin (~160-fold) in patient samples as compared with baseline. We also observed that NAC exposure significantly increased HO-1 expression in fibroblasts. CONCLUSION: Our data suggest that HO-1 is a possible target protein of NAC and a mediator of its cytoprotective effects in these patients. PMID- 26670325 TI - Comparing the burden of pancreatic fistulas after pancreatoduodenectomy and distal pancreatectomy. AB - BACKGROUND: Differences in the behavior of postoperative pancreatic fistulas (POPF) have been described after various pancreatic resections. Here, we compare POPFs after pancreatoduodenectomy (PD) and distal pancreatectomy (DP) using the average complication burden (ACB), a quantitative measure of complication burden. METHODS: From 2001 to 2014, 837 DPs and 1,533 PDs were performed by 14 surgeons at 4 institutions. POPFs were categorized by International Study Group on Pancreatic Fistula standards as biochemical (grade A) or clinically relevant (CR POPF; grades B and C). ACB values were derived from fistula severity scores based on the Modified Accordion Severity Grading. The ACB of POPFs was compared between PD and DP. RESULTS: POPFs were more common after DP compared with PD (34.5 vs 27.2%; P < .001); however, the incidence of any complication was greater after PD (64.9 vs 53.2%; P < .001). When POPFs occurred, they were more likely to be the highest-graded complication after DP compared with PD (65.1 vs 51.6%; P < .001). ACB significantly varied between PDs and DPs for grade C POPFs (0.804 vs 0.611; P < .001). POPFs accounted for 31.2% of the overall complication burden after DP compared with 17.5% of the burden after PD. ACB differed significantly across both institutions and surgeons in terms of POPFs, nonfistulous complications, and overall complications (all P < .05). CONCLUSION: Although POPFs occur less frequently after PD, they are associated with a greater complication burden compared with DP. ACB varies significantly between health care providers, suggesting the need for risk-adjusted comparisons of complication severity. Using ACB to evaluate a distinct morbidity has the potential to aid in assessing the impact of procedure-specific complications. PMID- 26670326 TI - Initial experience in sentinel lymph node detection in pancreatic cancer. AB - BACKGROUND: The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. MATERIALS AND METHODS: Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc(99m) labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. RESULTS: Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. CONCLUSIONS: This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation. PMID- 26670327 TI - Pharmacist and physician perspectives on diabetes service delivery within community pharmacies in Indonesia: a qualitative study. AB - OBJECTIVE: To explore perspectives of physicians and pharmacists on diabetes service delivery within community pharmacies in Indonesia. METHODS: In depth interviews were conducted with 10 physicians and 10 community pharmacists in Surabaya, Indonesia, using a semi-structured interview guide. Nvivo version 9 was used to facilitate thematic content analysis to identify barriers/facilitators for community pharmacists to provide diabetes services. KEY FINDINGS: The identified themes indicating barriers/facilitators for diabetes service delivery within Indonesian community pharmacies included: (1) pharmacist factors - i.e. positive views (facilitator) and perceived lack of competence (barrier); (2) pharmacist-physician relationships - i.e. physicians' lack of support and accessibility (barriers); (3) pharmacist-patient relationships - i.e. perceived patients' lack of support and accessibility (barriers); (4) pharmacy environment i.e. business orientation (barrier), lack of staff and poor pharmacist availability (barriers), and availability of supporting resources, such as counselling areas/rooms, procedures/protocols and IT systems for labelling and patient records (facilitators); and (5) external environment - i.e. a health system to support pharmacist roles, remuneration, marketing and professional assistance (facilitators). CONCLUSION: Issues related to the pharmacist-physician patient relationships, pharmacy environment and external environment need to be addressed before Indonesian community pharmacists can provide additional pharmacy services for type 2 diabetes patients. Collaboration between the Government, Ikatan Apoteker Indonesia (Indonesian Pharmacists Association) and Ikatan Dokter Indonesia (Indonesian Medical Association) is required to improve the pharmacy professional environment and facilities. PMID- 26670329 TI - Anti-Ro/SSA autoantibody-positive women's experience of information given on the risk of congenital heart block. AB - OBJECTIVE: Congenital heart block (CHB) may develop in fetuses of women with anti Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement. METHODS: A questionnaire was distributed to anti-Ro/SSA antibody positive women who had either participated in a surveillance programme but whose expected child did not develop CHB (n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB (n = 88, denoted CHB-Affected Pregnancies (CAP) group). RESULTS: The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information. CONCLUSIONS: Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information. PMID- 26670330 TI - Flexible Self-Powered GaN Ultraviolet Photoswitch with Piezo-Phototronic Effect Enhanced On/Off Ratio. AB - Flexible self-powered sensing is urgently needed for wearable, portable, sustainable, maintenance-free and long-term applications. Here, we developed a flexible and self-powered GaN membrane-based ultraviolet (UV) photoswitch with high on/off ratio and excellent sensitivity. Even without any power supply, the driving force of UV photogenerated carriers can be well boosted by the combination of both built-in electric field and piezoelectric polarization field. The asymmetric metal-semiconductor-metal structure has been elaborately utilized to enhance the carrier separation and transport for highly sensitive UV photoresponse. Its UV on/off ratio and detection sensitivity reach to 4.67 * 10(5) and 1.78 * 10(12) cm.Hz(0.5) W(1-), respectively. Due to its excellent mechanical flexibility, the piezoelectric polarization field in GaN membrane can be easily tuned/controlled based on piezo-phototronic effect. Under 1% strain, a stronger and broader depletion region can be obtained to further enhance UV on/off ratio up to 154%. As a result, our research can not only provide a deep understanding of local electric field effects on self-powered optoelectronic detection, but also promote the development of self-powered flexible optoelectronic devices and integrated systems. PMID- 26670328 TI - Pharmacological Inhibition of O-GlcNAcase Does Not Increase Sensitivity of Glucocorticoid Receptor-Mediated Transrepression. AB - Glucocorticoid signaling regulates target genes by multiple mechanisms, including the repression of transcriptional activities of nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB) though direct protein-protein interactions and subsequent O-GlcNAcylation of RNA polymerase II (pol II). Recent studies have shown that overexpression of O-linked beta-N-acetylglucosamine transferase (OGT), which adds an O-linked beta-N-acetylglucosamine (O-GlcNAc) group to the C-terminal domain of RNA pol II, increases the transrepression effects of glucocorticoids (GC). As O-GlcNAcase (OGA) is an enzyme that removes O GlcNAc from O-GlcNAcylated proteins, we hypothesized that the potentiation of GC effects following OGT overexpression could be similarly observed via the direct inhibition of OGA, inhibiting O-GlcNAc removal from pol II. Here we show that despite pharmacological evidence of target engagement by a selective small molecule inhibitor of OGA, there is no evidence for a sensitizing effect on glucocorticoid-mediated effects on TNF-alpha promoter activity, or gene expression generally, in human cells. Furthermore, inhibition of OGA did not potentiate glucocorticoid-induced apoptosis in several cancer cell lines. Thus, despite evidence for O-GlcNAc modification of RNA pol II in GR-mediated transrepression, our data indicate that pharmacological inhibition of OGA does not potentiate or enhance glucocorticoid-mediated transrepression. PMID- 26670331 TI - Effects of threonine supplementation on whole-body protein synthesis and plasma metabolites in growing and mature horses. AB - Current equine threonine requirement estimates do not account for probable use of threonine to maintain gut health and mucin synthesis. The objective of this study was to determine if threonine supplementation (+Thr) would increase whole-body protein synthesis (WBPS) in weanling colts (Study 1) and adult mares (Study 2). Both studies used a crossover design, where each of six animals was studied twice while receiving the isonitrogenous diets. The basal diets contained lower threonine levels (Basal) than the threonine (+Thr) supplemented diets. Threonine intakes in mg/kg BW/day were as follows: 79 (Basal) and 162 (+Thr) for Study 1 and 58 (Basal) and 119 (+Thr) for Study 2, in comparison to the NRC estimated requirements of 81 and 33 mg/kg BW/day for weanling and mature horses, respectively. Following 5 days of adaptation, blood samples were taken before and 90 min after the morning concentrate meal. The next day, whole-body phenylalanine kinetics were determined using a 2 h primed, constant infusion of [(13)C]sodium bicarbonate followed by a 4 h primed, constant infusion of [1 (13)C]phenylalanine. Most plasma amino acid (AA) concentrations were elevated post-feeding (P < 0.01). Lysine and valine plasma concentrations were lower (P <0.10), while methionine, threonine, and glycine plasma concentrations were greater (P <0.10) 90 min post concentrate meal feeding with +Thr in both studies. Phenylalanine flux, intake, oxidation and non-oxidative disposal were similar between treatments (P > 0.05). These findings suggest that supplementation of a single AA can affect the metabolism of several AAs and threonine was not a limiting AA in these diets. PMID- 26670332 TI - Prevalence and characteristics of osteochondrosis in 309 Spanish Purebred horses. AB - Articular osteochondrosis (OC) is commonly reported in horses but there are no reports of its prevalence in the Spanish Purebred (SP). The objective of this study was to assess the prevalence and characteristics of OC of the tarsocrural, dorsal metacarpo-metatarsophalangeal and femoropatellar joints in the SP in a retrospective study. The data were obtained from the radiographs of 309 SP horses and the prevalence and characteristics of lesions were calculated. Osteochondral lesions at predilected sites were diagnosed in 48.8% of the horses. It was more common to find the presence of fragments (28.8%) than flattening of the subchondral bone contour (20.1%). The percentage with abnormal articular margins was 1.3% for the femoropatellar joint, 33.3% for the tarsocrural and 25% for the dorsal fetlock region, where flattening was more common than the presence of fragments; in the tarsus and stifle, fragments were more common. The severity of the disease in the dorsal fetlock area was higher in hindlimbs than in forelimbs. Femoropatellar lesions were rare. Osteochondrosis is a common disease in the SP and this study provides information about the prevalence of osteochondrosis lesions in the breed and the interrelationships between the joints. PMID- 26670333 TI - Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function. AB - Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias. PMID- 26670334 TI - Change in vascular smooth muscle response to 5-HT due to short- or long-term endothelial denudation of the bovine digital vein. AB - Several chronic progressive vascular diseases, such as laminitis, show vasocontractile dysfunction that might evolve into reperfusion injury and/or vessel structural remodelling, which may be traced back to aberrant endothelial function. In the present study, the vasomotor responses of bovine digital veins (BDVs) to 5-hydroxytryptamine (5-HT) were investigated in blood vessels, with and without endothelium present, and in samples deprived of endothelium before or after overnight incubation in tissue culture medium, to evaluate the effects of short- and long-term endothelial damage on vascular smooth muscle (VSM) reactivity. No significant effects were observed in the blood vessels tested immediately after the removal of endothelium. In contrast, a significant increase in VSM reactivity to 5-HT was seen in vessels incubated without endothelium. This long-term change in smooth muscle reactivity was prevented by exposure to the nitric oxide (NO) donor nitroprusside (P < 0.01), suggesting that the long-term lack of inhibitory control exerted by endothelium-derived NO is involved in increased VSM reactivity. The RhoA/ROCK pathway inhibitor fasudil reduced VSM hyper-contractility to ~65% (P < 0.001), the superoxide dismutase-mimetic tempol normalised the vascular response and the non-selective COX-inhibitor indomethacin exerted a moderate inhibitory effect (P < 0.05). Thus, over-activation of the RhoA/ROCK pathway and production of reactive oxygen species could account for VSM hyper-reactivity, triggered by long-term endothelium-deprivation in BDVs, suggesting that these biochemical mechanisms are potential targets for controlling the progressive vasocontractile dysfunction of digital veins in animals affected with laminitis. PMID- 26670335 TI - Mutation Screening of 1,237 Cancer Genes across Six Model Cell Lines of Basal Like Breast Cancer. AB - Basal-like breast cancer is an aggressive subtype generally characterized as poor prognosis and lacking the expression of the three most important clinical biomarkers, estrogen receptor, progesterone receptor, and HER2. Cell lines serve as useful model systems to study cancer biology in vitro and in vivo. We performed mutational profiling of six basal-like breast cancer cell lines (HCC38, HCC1143, HCC1187, HCC1395, HCC1954, and HCC1937) and their matched normal lymphocyte DNA using targeted capture and next-generation sequencing of 1,237 cancer-associated genes, including all exons, UTRs and upstream flanking regions. In total, 658 somatic variants were identified, of which 378 were non-silent (average 63 per cell line, range 37-146) and 315 were novel (not present in the Catalogue of Somatic Mutations in Cancer database; COSMIC). 125 novel mutations were confirmed by Sanger sequencing (59 exonic, 48 3'UTR and 10 5'UTR, 1 splicing), with a validation rate of 94% of high confidence variants. Of 36 mutations previously reported for these cell lines but not detected in our exome data, 36% could not be detected by Sanger sequencing. The base replacements C/G>A/T, C/G>G/C, C/G>T/A and A/T>G/C were significantly more frequent in the coding regions compared to the non-coding regions (OR 3.2, 95% CI 2.0-5.3, P<0.0001; OR 4.3, 95% CI 2.9-6.6, P<0.0001; OR 2.4, 95% CI 1.8-3.1, P<0.0001; OR 1.8, 95% CI 1.2-2.7, P = 0.024, respectively). The single nucleotide variants within the context of T[C]T/A[G]A and T[C]A/T[G]A were more frequent in the coding than in the non-coding regions (OR 3.7, 95% CI 2.2-6.1, P<0.0001; OR 3.8, 95% CI 2.0-7.2, P = 0.001, respectively). Copy number estimations were derived from the targeted regions and correlated well to Affymetrix SNP array copy number data (Pearson correlation 0.82 to 0.96 for all compared cell lines; P<0.0001). These mutation calls across 1,237 cancer-associated genes and identification of novel variants will aid in the design and interpretation of biological experiments using these six basal-like breast cancer cell lines. PMID- 26670336 TI - Enhanced SRSF5 Protein Expression Reinforces Lamin A mRNA Production in HeLa Cells and Fibroblasts of Progeria Patients. AB - The Hutchinson Gilford Progeria Syndrome (HGPS) is a rare genetic disease leading to accelerated aging. Three mutations of the LMNA gene leading to HGPS were identified. The more frequent ones, c.1824C>T and c.1822G>A, enhance the use of the intron 11 progerin 5'splice site (5'SS) instead of the LMNA 5'SS, leading to the production of the truncated dominant negative progerin. The less frequent c.1868C>G mutation creates a novel 5'SS (LADelta35 5'SS), inducing the production of another truncated LMNA protein (LADelta35). Our data show that the progerin 5'SS is used at low yield in the absence of HGPS mutation, whereas utilization of the LADelta35 5'SS is dependent upon the presence of the c.1868C>G mutation. In the perspective to correct HGPS splicing defects, we investigated whether SR proteins can modify the relative yields of utilization of intron 11 5'SSs. By in cellulo and in vitro assays, we identified SRSF5 as a direct key regulator increasing the utilization of the LMNA 5'SS in the presence of the HGPS mutations. Enhanced SRSF5 expression in dermal fibroblasts of HGPS patients as well as PDGF-BB stimulation of these cells decreased the utilization of the progerin 5'SS, and improves nuclear morphology, opening new therapeutic perspectives for premature aging. PMID- 26670337 TI - Covariation between Spike and LFP Modulations Revealed with Focal and Asynchronous Stimulation of Receptive Field Surround in Monkey Primary Visual Cortex. AB - A focal visual stimulus outside the classical receptive field (RF) of a V1 neuron does not evoke a spike response by itself, and yet evokes robust changes in the local field potential (LFP). This subthreshold LFP provides a unique opportunity to investigate how changes induced by surround stimulation leads to modulation of spike activity. In the current study, two identical Gabor stimuli were sequentially presented with a variable stimulus onset asynchrony (SOA) ranging from 0 to 100 ms: the first (S1) outside the RF and the second (S2) over the RF of primary visual cortex neurons, while trained monkeys performed a fixation task. This focal and asynchronous stimulation of the RF surround enabled us to analyze the modulation of S2-evoked spike activity and covariation between spike and LFP modulation across SOA. In this condition, the modulation of S2-evoked spike response was dominantly facilitative and was correlated with the change in LFP amplitude, which was pronounced for the cells recorded in the upper cortical layers. The time course of covariation between the SOA-dependent spike modulation and LFP amplitude suggested that the subthreshold LFP evoked by the S1 can predict the magnitude of upcoming spike modulation. PMID- 26670338 TI - Frequency, natural course and clinical significance of symptomatic terminal ileitis. AB - OBJECTIVE: Treatment guidelines for managing symptomatic terminal ileitis (TI) are lacking. We followed up a cohort of symptomatic TI patients to conduct an algorithm for their management. METHODS: Consecutive patients with symptomatic TI from July 2007 to October 2013 were included. Symptomatic TI was defined as isolated terminal ileum ulceration (superficial or deep) and/or nodularity with abdominal symptoms. Patients were diagnosed either with intestinal tuberculosis (ITB) or Crohn's disease (CD) using standard criteria or received only symptomatic treatment according to their clinical manifestations, endoscopic, imaging and histological (specific to ITB/CD vs non-specific) features. Based upon above findings, an algorithm was conducted to differentiate non-specific TI from those with specific etiology (ITB/CD). RESULTS: In all, 63/898 (7.0%) patients with ulcero-constrictive intestinal disease had TI, of which 45 (26 males and 19 females) were included. Fever, diarrhea, weight loss, deep ulcers, and ileal thickening were more frequently observed in patients with ITB or CD having specific treatments compared with those receiving symptomatic treatments. All patients with deep ulcers and those with superficial ulcer and specific histology had ITB/CD. In patients with superficial ulcers and/or nodularity and non-specific inflammation (n = 31), the absence of fever, diarrhea, GI bleeding or weight loss had a negative predictive value of 92% in excluding ITB/CD. CONCLUSIONS: In symptomatic TI patients with superficial ulcers and a non specific histology, the absence of fever, diarrhea, GI bleeding or weight loss rules out the possibility of significant diagnoses like ITB/CD. PMID- 26670339 TI - Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus. AB - AIMS: Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. METHODS: PUA, GFR (inulin) and effective renal plasma flow (ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent (RA ) and efferent (RE ) arteriolar resistances, glomerular hydrostatic pressure (PGLO ) and filtration pressure (DeltaPF ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. RESULTS: In patients with Type 1 diabetes, higher PUA correlated with lower PGLO (P = 0.002) and DeltaPF (P = 0.0007), with higher RA (P = 0.001), but not with RE (P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR (P = 0.0007), ERPF (P = 0.008), RBF (P = 0.047) and higher RVR (P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. CONCLUSIONS: The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA . PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation. PMID- 26670340 TI - Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition. AB - PURPOSE: The aim of this paper was to synthesise core-shell nanostructures comprised of mesoporous silica core and a low melting-point polyethylene glycol (PEG) nanoshell with a sharp gel-liquid phase transition for rapid drug release at hyperthermia temperature range. MATERIALS AND METHODS: The phase transition behaviours of PEGs with molecular weights of 1000, 1500, and 2000 Da were analysed using differential scanning calorimetry (DSC) to determine the optimal formulation with phase transition in the hyperthermia range. The 'graft-to' method was employed to synthesise core-shell nanostructures using the selected PEG formulation. The drug loading and release behaviours of these nanocarriers were examined by ultra-violet visible spectroscopy (UV-Vis) using doxorubicin as a model drug. Magnetic resonance-guided focused ultrasound (MRgFUS) was also applied as a typical thermal modality to evaluate the rate of drug release from the core-shell nanostructures. RESULTS: The PEG molecular weight of 1500 Da presented the optimal phase transition temperature for thermal-triggered release under hyperthermia conditions. Drug release measurements at different temperatures using UV-Vis methods showed a 20.2 +/- 4.3% leakage in aqueous solution at 37 degrees C after 30 min, while this value was significantly increased to 68.2 +/- 3.7% at 50 degrees C. A 45.5 +/- 3.1% drug release was also obtained after sonication of the drug-loaded nanoparticles for 5 * 20 s using MRgFUS. CONCLUSION: Although the ratio of drug leakage at physiological temperatures was relatively high, the sharp transition temperature, high loading efficiency, and fast drug release at hyperthermia temperature range could make these core-shell nanoparticles prominent for enhancing the efficacy of various hyperthermia modalities in the treatment of cancer tumours. PMID- 26670341 TI - Commentaries on Viewpoint: Using the same cut-off for sulfur hexafluoride and nitrogen multiple-breath washout may not be appropriate. PMID- 26670342 TI - Last Word on Viewpoint: Using the same cut-off for sulfur hexafluoride and nitrogen multiple-breath washout may not be appropriate. PMID- 26670343 TI - Commentaries on Viewpoint: Inappropriate interpretation of surface EMG signals and muscle fiber characteristics impedes understanding of the control of neuromuscular function. PMID- 26670344 TI - Less peripheral fatigue after prior exercise is not evidence against the regulation of the critical peripheral fatigue threshold. PMID- 26670345 TI - Reply to Broxterman, Richardson, and Amann. PMID- 26670346 TI - Fatty acid composition of chicken breast meat is dependent on genotype-related variation of FADS1 and FADS2 gene expression and desaturating activity. AB - In Western countries the dietary guidance emphasizes the need to decrease the intake of saturated fatty acids and to replace them with polyunsaturated fatty acids (PUFA), particularly long chain n-3 PUFA (LC-PUFA). The production of poultry meat having a lower fat content and healthier fatty acid (FA) profile is a hot topic for the poultry industry, and the possibility to identify genotypes able to produce meat with a higher LC-PUFA content deserves attention. The aims of the present study were to evidence in chicken (i) a genotype-related different expression of the desaturating enzymes delta-6 (Delta6, EC 1.14.99.25), delta-5 (Delta5, EC 1.14.19.) and delta-9 (Delta9, EC 1.14.19.1); (ii) the impact of the hypothesized different expression on the meat FA composition; (iii) the distribution of desaturase products in the different lipid classes. Slow (SG), medium (MG) and fast (FG) growing chickens fed the same diet were evaluated either for the relative expression of FADS1, FADS2 and SCD1 genes in liver (by q PCR), or for the FA composition of breast meat. MG and particularly SG birds showed a greater expression of FADS2 and FADS1 genes, a higher Delta6 and Delta5 activity (estimated using desaturase indices), and consequently a higher LC-PUFA content in the breast meat than FG birds. The relationship between genotype and desaturating ability was demonstrated, with a significant impact on the PUFA content of breast meat. Due to the high consumption rate of avian meat, the identification of the best genotypes for meat production could represent an important goal not only for the food industry, but also for the improvement of human nutrition. PMID- 26670347 TI - Description and Role of Bimetallic Prenucleation Species in the Formation of Small Nanoparticle Alloys. AB - We report the identification, description, and role of multinuclear metal thiolate complexes in aqueous Au-Cu nanoparticle syntheses. The structure of these species was characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy techniques. The observed structures were found to be in good agreement with thermodynamic growth trends predicted by first-principles calculations. The presence of metal-thiolate complexes is then shown to be critical for the formation of alloyed Au-Cu architectures in the small nanoparticle regime (diameter ~2 nm). In the absence of mixed metal-thiolate precursors, nanoparticles form with a Cu-S shell and a Au-rich interior. Taken together, these results demonstrate that prenucleation species, which are discrete molecular precursors distinct from both initial reagents and final particle products, may provide an important new synthetic route to control final metal nanoparticle composition and composition architectures. PMID- 26670348 TI - Substance use and misuse in burn patients: Testing the classical hypotheses of the interaction between post-traumatic symptomatology and substance use. AB - The authors aimed to test whether the three classical hypotheses of the interaction between post-traumatic symptomatology and substance use (high risk of trauma exposure, susceptibility for post-traumatic symptomatology, and self medication of symptoms), may be useful in the understanding of substance use among burn patients. Substance use data (nicotine, alcohol, cannabis, amphetamines, cocaine, opiates, and tranquilizers) and psychopathology measures among burn patients admitted to a burn unit and enrolled in a longitudinal observational study were analyzed. Lifetime substance use information (n = 246) was incorporated to analyses aiming to test the high risk hypothesis. Only patients assessed for psychopathology in a 6-month follow-up (n = 183) were included in prospective analyses testing the susceptibility and self-medication hypotheses. Regarding the high risk hypothesis, results show a higher proportion of heroin and tranquilizer users compared to the general population. Furthermore, in line with the susceptibility hypothesis, higher levels of symptomatology were found in lifetime alcohol, tobacco, and drug users during recovery. The self medication hypothesis could be tested partially due to the hospital stay "cleaning" effect, but severity of symptoms was linked to the amount of caffeine, nicotine, alcohol, and cannabis use after discharge. It was found that the 3 classical hypotheses could be used to understand the link between traumatic experiences and substance use explaining different patterns of burn patient's risk for trauma exposure and emergence of symptomatology. PMID- 26670349 TI - Usefulness of biomarkers as intermediate endpoints in health risks posed by occupational lead exposure. AB - The article concerns potential harmful effects of exposure to lead. Although the occurrence of severe lead poisoning has receded in several countries, occupational exposure resulting in moderate and clinically symptomatic toxicity is still common. An earlier and precise characterization of an individual response is obligatory in order to assess the possible risks for human health. Biomarkers may fill important gaps in the path from exposure to a disease. Specifically speaking, emerging (DNA double strand breaks and telomeric DNA erosion) and validated (micronuclei induction and chromosomal aberrations) biomarkers of genotoxicity seem to provide evidence for the assessment of molecular and cellular damage. Moreover, identification of genetic variability with a key role in modulating genotoxic damage may help minimize risks for susceptible subjects. Further investigations are naturally needed to properly define their diagnostic and/or prognostic value as "early warning" signs of a long-term risk for a subsequent clinically overt disease. PMID- 26670350 TI - Isoprostanes - A novel major group of oxidative stress markers. AB - Isoprostanes are a recently discovered group of prostaglandin isomers. Results of previous studies suggest that they can be used as oxidative stress markers, because in a number of cardiovascular, pulmonary and neurological diseases their levels in biological samples considerably increase. It has been found that people suffering from diabetes, obesity, homozygous familial hypercholesterolemia, moderate hypercholesterolemia, and smokers have higher levels of isoprostanes in urine. The same refers to patients with asthma, Alzheimer disease and Down syndrome. This paper reviews the results of relevant studies. PMID- 26670351 TI - Heaviness of smoking among employed men and women in Poland. AB - OBJECTIVES: At least 50% of smokers die prematurely. Those who smoke heavily are at an increased health risk. The purpose of the current report was to evaluate socio-demographic correlates of heavy smoking among employed men and women. MATERIAL AND METHODS: Data derive from the representative, household study - the Global Adult Tobacco Survey conducted in Poland over the years 2008-2010. RESULTS: Of 14 000 households selected for the survey, 7840 sampled individuals completed the interviews. Among 1189 daily smokers, the rate of heavy smokers was 63.5% in males and 43% in employed females (p < 0.001). The study showed that age and age at the smoking onset were significantly associated with heavy smoking among both genders. Among males and females the heavy smoking rate was the highest in the subjects that started smoking at the age between 14-17 years compared to those who started smoking at the age >= 21 years (odds ratio (OR) = 3.3, 95% confidence interval (CI): 2-5.5, p < 0.001 and OR = 2.7, 95% CI: 1.4 5.3, p < 0.0001, respectively). The men with house rules that prohibited smoking with some exceptions were 2.4 times more likely to be heavy smokers in comparison with those having rules which completely prohibited it (p < 0.01). The men working in workplaces where smoking was prohibited in all indoor areas were at lower odds of heavy smoking relative to those working in areas where smoking was allowed everywhere (OR = 0.5, 95% CI: 0.3-0.9, p < 0.05). Among the men, there was also an association between job features and heavy smoking, which was not observed among the women. CONCLUSIONS: These findings should be taken into account while developing tobacco control measures addressed to economically active population. PMID- 26670352 TI - Health benefits related to the reduction of PM concentration in ambient air, Silesian Voivodeship, Poland. AB - OBJECTIVES: Health Impact Assessments (HIA) approach can be executed by calculating the attributable burden of disease. The most common indicators used in the HIA methodology are: premature mortality, morbidity, life-expectancy, and Disability Adjusted Life-Year (DALY). The term Disability Adjusted Life-Years (DALYs) indicates months/years lost due to a premature death or disability. The aim of the study was to present health benefits, expressed in terms of lower total mortality and cardio-respiratory hospitalization rates, due to a decreased particulate matter (PM) concentration in ambient air, in Silesian voivodeship. MATERIAL AND METHODS: In this paper, results obtained from the APHEKOM (Improving Knowledge and Communication for Decision Making on Air Pollution and Health in Europe) project, which provided specialized HIA tools, useful for assessing health benefits resulting from reducing air pollution, were used. Both short-term and long-term exposure HIA tools were applied with regard to the appropriate data for Silesian voivodeship. Exposure data were obtained from the Regional Environmental Inspectorate in Katowice, while population and health data were obtained from the Central Statistical Office of Poland or from the Silesian Voivodeship Office, respectively. RESULTS: Health benefits that are related to an improvement of ambient air quality in Silesia region are similar to previous estimates obtained for Krakow city. The reduction of short-term exposure to PM10 by 5 MUg/m3 results in a lower number of yearly non-external deaths (2.6-2.75 per 100 000 inhabitants). This effect was also shown to be similar in the city of Zabrze, as well as in the whole Silesia region. CONCLUSIONS: The Health Impact Assessments tools developed by the World Health Organization (WHO) can help public health experts make decisions in order to improve the health of populations living in particular regions of Europe. PMID- 26670353 TI - Blood lead determinants and the prevalence of neuropsychiatric symptoms in firearm users in Mexico. AB - OBJECTIVES: To identify blood lead predictors and the prevalence of neuropsychiatric symptoms in firearm users of public security in Mexico. MATERIAL AND METHODS: A cross-sectional study was performed on 65 males. We obtained socio occupational data and determined venous blood lead (blood (B), lead (Pb) - BPb), as well as neuropsychiatric symptoms using the Q-16 questionnaire. A multiple linear regression model was constructed to assess determinants of BPb. RESULTS: The mean age in the study group was 34.8 years (standard deviation (SD) = 6.9, range: 21-60); the mean number of years spent in the company amounted to 14 years (SD = 8.5, range: 1-48). Twenty percent of the respondents (N = 13) used leaded glazed clay pottery (lead (Pb), glazed (G), and clay pottery (C) - PbGC) in the kitchen. During practice they fired a mean of 72 shots (SD = 60, range: 20-250), and during their whole duration of employment 5483 shots (SD = 8322.5, range: 200 50 000). The mean BPb was 7.6 MUg/dl (SD = 6.8, range: 2.7-51.7). Two caretakers from the firing range had 29.6 MUg/dl and 51.7 MUg/dl BPb. The subjects who had shooting practice sessions >= 12 times a year reported a greater percentage of miscarriages in their partners (24% vs. 0%). Twelve percent of the respondents showed an increase in neuropsychiatric symptoms. The BPb multiple linear regression model explained R2 = 44.15%, as follows: those who had >= 12 practice sessions per year - beta = 0.5339 and those who used PbGC - beta = 0.3651. CONCLUSIONS: Using firearms and PbGC contributes to the increased BPb in the studied personnel. The determinants of BPb were: shooting practices >12 times a year and using PbGC. Blood lead concentrations reported in the study, despite being low, are a health risk, as evidenced by the prevalence of neuropsychiatric symptoms. PMID- 26670354 TI - Health Impact Assessment of an oil drilling project in California. AB - OBJECTIVES: The Health Impact Assessment (HIA) was conducted to evaluate the potential community health implications of a proposed oil drilling and production project in Hermosa Beach, California. The HIA considered 17 determinants of health that fell under 6 major categories (i.e., air quality, water and soil quality, upset conditions, noise and light emissions, traffic, and community livability). MATERIAL AND METHODS: This paper attempts to address some of the gaps within the HIA practice by presenting the methodological approach and results of this transparent, comprehensive HIA; specifically, the evaluation matrix and decision-making framework that have been developed for this HIA and form the basis of the evaluation and allow for a clear conclusion to be reached in respect of any given health determinant (i.e., positive, negative, neutral). RESULTS: There is a number of aspects of the project that may positively influence health (e.g., increased education funding, ability to enhance green space), and at the same time there have been potential negative effects identified (e.g., odor, blowouts, property values). Except for upset conditions, the negative health outcomes have been largely nuisance-related (e.g., odor, aesthetics) without irreversible health impacts. The majority of the health determinants, that had been examined, have revealed that the project would have no substantial effect on the health of the community. CONCLUSIONS: Using the newly developed methodology and based on established mitigation measures and additional recommendations provided in the HIA, the authors have concluded that the project will have no substantial effect on community health. This approach and methodology will assist practitioners, stakeholders and decision-makers in advancing the HIA as a useful, reproducible, and informative tool. PMID- 26670355 TI - Exposure to culturable and total microbiota in cultural heritage conservation laboratories. AB - OBJECTIVES: To date, the scientific source materials usually focus on microbial contamination of the museum or library collections themselves, while the exposure of persons who professionally deal with this type of objects in cultural heritage conservation laboratories is ignored. MATERIAL AND METHODS: The study was carried out in 9 naturally ventilated conservation laboratories with no history of water damage. Viable (understood as culturable) bioaerosol stationary samples were collected in both outdoor and indoor environments using 6-stage Andersen impactor. Simultaneously, stationary and personal indoor bioaerosol measurements were carried out using both Gesamtstaubprobenahme an der Person (GSP) and Button filter samplers. These measurements were complemented by evaluation of microbial content in the dust settled on conserved works of art. All impactor, filter, and settled dust samples were quantitatively examined to obtain viable and total concentrations of bacteria and fungi. All isolated microbial strains were taxonomically identified. RESULTS: At workplaces, the concentrations of viable microorganisms in air were below 2000 cfu/m3 and accounted for not more than 5.5% of total microbiota. The study showed that quantitative assessment of viable bioaerosol can be made with an Andersen impactor as well as by using Button and GSP filter samplers, irrespective of whether they are applied for personal or stationary measurements. Compared to the impactor, however, the use of filter samplers for microbial contamination monitoring substantially limits the scope of qualitative information which can be obtained. Size distribution analysis revealed that the largest "load" of microorganisms can penetrate into the respiratory tract between the trachea and terminal bronchi, and thereby may be responsible for allergic inflammations in exposed workers. CONCLUSIONS: The precise assessment of microbial hazards in conservation laboratories should comprise control of both viable and total particle counts. The hermetization of such workplaces and control of relative humidity should be implemented and maintained to assure proper hygienic conditions. PMID- 26670357 TI - Expression of cytochrome P450 2C and 3A in female rat liver after long-term administration of gonadoliberin analogs. AB - OBJECTIVES: Gonadoliberin (GnRH) analogs may be expected to indirectly modify growth hormone (GH) total concentration and its 24-h secretion profile. As a consequence, changes in the levels of GH may modify the mechanism of sex dependent cytochromes P450 (CYP450) synthesis, including the expression of transcriptional factors. The aim of the study has been to evaluate the effect of long-term administration of a low dose of GnRH analogs on hepatic expression of CYP2C and CYP3A isoforms, and the transcription factors: pregnane X receptor (PXR), hepatocyte nuclear factor 4alpha (HNF4alpha), HNF6 and signal transducers and activators of transcription 5b (STAT5b). MATERIAL AND METHODS: The study was carried out on adult female Sprague-Dawley rats during a 3-month treatment with dalarelin (GnRH agonist) and cetrorelix (GnRH antagonist), at a daily intraperitoneal injection (i.p.) dose of 6 MUg/kg body weight/day, and 1, 2, and 4 weeks after treatment discontinuation. The concentrations of ovarian hormones and GH in the blood serum were determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) method, respectively. Then, the expression of hepatic CYP450s (reverse transcription polymerase chain reaction - RT-PCR, Western blot and immunohistochemistry) and transcription factors (RT-PCR) was evaluated. RESULTS: We have found that cetrorelix induces changes in the circadian pattern of GH secretion and enhances GH blood concentrations. These changes may cause increased expression of both, female-specific CYP450s (especially CYP3A9), and HNF4alpha/HNF6 transcription factors. Decrease in GH blood concentrations, resulting from the effect of dalarelin, may promote inhibition of female-specific CYP2C12 and CYP3A9 isoforms as well as STAT5b transcription factor. Slight changes in sex-independent CYP3A1 protein expression caused by GnRH analogs were also observed. CONCLUSIONS: In adult female rats, HNF4alpha/HNF6 and STAT5b seem to be crucial for the regulation of GnRH antagonist/GH- and GnRH agonist/GH dependent pattern of CYP450 expression, respectively. PMID- 26670356 TI - Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice. AB - OBJECTIVES: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs) on the immune function of splenic lymphocytes in mice. MATERIAL AND METHODS: Twenty male Kunming mice (6 weeks old), weighing 18- 25 g, were randomly divided into sham exposure (N = 10) and 500 MUT MFs (N = 10) groups. The mice in the MFs group were exposed to 500 MUT MFs for 8 h daily (5 days/week) for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69) in mouse prime splenic lymphocytes activated by para Methoxyamphetamine (PMA) and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640) and exposed to 0 MUT, 250 MUT, 500 MUT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2) at 37 degrees C for 6 h. The levels of interleukin-2 (IL-2), IL-4, interferon gamma (IFN-gamma), GATA binding protein 3 (GATA-3) and T cell-specific T-box transcription factor (T-bet) were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. The expression of CD69 was checked using the flow cytometry. RESULTS: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs) significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. CONCLUSIONS: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic lymphocytes in mice, except for body weight. PMID- 26670358 TI - Sickness absence in workplaces: Does it reflect a healthy hire effect? AB - OBJECTIVES: Sickness absence in workplaces may reflect working conditions. It may also reflect a "healthy hire effect," i.e., that workplaces recruit individuals with experience of sickness absence differently. The purpose of the study was to determine if a history of sickness absence among recruits is associated with the average level of sickness absence in workplaces. MATERIAL AND METHODS: In a register-based follow-up study, Swedish workplaces with at least 5 employees in 2006 were selected (approximately 127 000 workplaces with 3.9 million employees). The workplaces were categorized according to the average workplace sickness absence in 2006 and the recruits were categorized according to the individual sickness absence in 2005. The workplaces with a high average level of sickness absence were more likely than those with a low level to hire employees with high sickness absence in the year preceding employment: men - odds ratio (OR) = 7.2, 95% confidence interval (CI): 6.6-7.8, women - OR = 7.5, 95% CI: 6.9-8.1. RESULTS: The results show that there is a greater likelihood of employing individuals with high levels of sickness absence in the workplaces with many days of the average sickness absence than in the workplaces with few days of the average sickness absence. CONCLUSIONS: The results suggest that sickness absence in workplaces may reflect a healthy hire effect. PMID- 26670359 TI - Association between psychosocial characteristics of work and presenteeism: A cross-sectional study. AB - OBJECTIVES: This study aimed at investigating cross-sectional relationships between psychosocial characteristics of work and presenteeism in a sample of Belgian middle-aged workers. MATERIAL AND METHODS: Data were collected from 1372 male and 1611 female workers in the Belstress III study. Psychosocial characteristics assessed by the use of self-administered questionnaires were: job demands, job control, social support, efforts, rewards, bullying, home-to-work conflict and work-to-home conflict. Presenteeism was measured using a single item question, and it was defined as going to work despite illness at least 2 times in the preceding year. Logistic regression models were used to investigate the relationship between psychosocial characteristics and presenteeism, while adjusting for several socio-demographic, health-related variables and neuroticism. An additional analysis in a subgroup of workers with good self-rated health and low neuroticism was conducted. RESULTS: The prevalence of presenteeism was 50.6%. Overall results, adjusted for major confounders, revealed that high job demands, high efforts, low support and low rewards were associated with presenteeism. Furthermore, a significant association could be observed for both bullying and work-to-home conflict in relation to presenteeism. The subgroup analysis on a selection of workers with good self-rated health and low neuroticism generally confirmed these results. CONCLUSIONS: Both job content related factors as well as work contextual psychosocial factors were significantly related to presenteeism. These results suggest that presenteeism is not purely driven by the health status of a worker, but that psychosocial work characteristics also play a role. PMID- 26670360 TI - Shoulder girdle muscle activity and fatigue in traditional and improved design carpet weaving workstations. AB - OBJECTIVES: Work-related musculoskeletal disorders in the neck and shoulder regions are common among carpet weavers. Working for prolonged hours in a static and awkward posture could result in an increased muscle activity and may lead to musculoskeletal disorders. Ergonomic workstation improvements can reduce muscle fatigue and the risk of musculoskeletal disorders. MATERIAL AND METHODS: The aim of this study is to assess and to compare upper trapezius and middle deltoid muscle activity in 2 traditional and improved design carpet weaving workstations. These 2 workstations were simulated in a laboratory and 12 women carpet weavers worked for 3 h. Electromyography (EMG) signals were recorded during work in bilateral upper trapezius and bilateral middle deltoid. The root mean square (RMS) and median frequency (MF) values were calculated and used to assess muscle load and fatigue. Repeated measure ANOVA was performed to assess the effect of independent variables on muscular activity and fatigue. The participants were asked to report shoulder region fatigue on the Borg's Category-Ratio scale (Borg CR-10). RESULTS: Root mean square values in workstation A are significantly higher than in workstation B. Furthermore, EMG amplitude was higher in bilateral trapezius than in bilateral deltoid. However, muscle fatigue was not observed in any of the workstations. CONCLUSIONS: The results of the study revealed that muscle load in a traditional workstation was high, but fatigue was not observed. Further studies investigating other muscles involved in carpet weaving tasks are recommended. PMID- 26670362 TI - Relationship between Caffeine and Levels of DNA Repair and Oxidative Stress in Women with and without a BRCA1 Mutation. AB - BACKGROUND: Coffee consumption has been associated with a reduction in breast cancer risk among women with a BRCA1 mutation. The objective of this study was to evaluate whether major contributors of caffeine intake are associated with a reduction in DNA damage and/or oxidative stress in women with and without a BRCA1 mutation. METHODS: Coffee, tea, soda and total caffeine consumption was collected by a dietary history questionnaire, and DNA repair capacity in lymphocytes was assessed by the comet assay (tail moments), micronucleus test (per 1,000 binucleated cells) and analysis of gamma-H2AX staining (nuclear foci). The thiobarbituric acid-malondialdehyde and DTNB assays were used to estimate serum lipid peroxidation (umol/l) and protein oxidation (umol/l), respectively. RESULTS: Among all women, high levels of caffeine and caffeinated coffee intake were associated with significantly lower levels of micronuclei (138.50 vs. 97.67, p = 0.04, and 138.12 vs. 97.70, p = 0.04). There was no significant relationship between caffeine, coffee, tea and soda intake and the other markers of DNA repair capacity and oxidative stress among all women and in analyses stratified by BRCA1 mutation status. CONCLUSION: The chemopreventive effects of coffee and/or caffeine may be associated with improved capacity to efficiently repair DNA damage. PMID- 26670361 TI - Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary. AB - The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. PMID- 26670363 TI - Long-term follow up of peginterferon-alpha-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies. AB - AIM: We analyzed the 5-year post-treatment response to peginterferon alpha-2a (PEG IFN-alpha-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients. METHODS: One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90 MUg or 180 MUg of PEG IFN-alpha-2a for 24 or 48 weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C. RESULTS: Of the 137 patients, 94 received additional antiviral therapy because of viral reactivation and 43 did not receive any additional antiviral treatment during follow up. Five years upon PEG IFN-alpha-2a treatment, 32 patients (23.4%) who did not receive any additional antiviral agent after PEG IFN-alpha-2a therapy achieved a good response (normal serum alanine aminotransferase, low-level hepatitis B virus [HBV] DNA, and HBeAg negativity). Female sex and low HBV DNA levels by the end of treatment were independently associated with favorable 5-year post-treatment responses. Forty-eight-week administration of PEG IFN-alpha-2a showed a better response (26.4%) than 24-week administration (18.0%). Six patients (4.3%), four males and two females, cleared hepatitis B surface antigen (HBsAg) during the 5-year follow-up period. CONCLUSION: The 48-week administration of PEG IFN-alpha-2a achieved better biochemical and virological responses than the 24-week administration, particularly in younger females. The 5-year post-treatment response rate was 23.4%; however, more than two-thirds of the patients received additional antiviral therapy because of viral reactivation after PEG IFN-alpha-2a treatment. HBsAg clearance was noted in six patients (4.3%). PEG IFN-alpha-2a is effective in young female patients. PMID- 26670364 TI - A Rapid and Sensitive HPLC Method for Quantitation of Paclitaxel in Biological Samples using Liquid-Liquid Extraction and UV Detection: Application to Pharmacokinetics and Tissues Distribution Study of Paclitaxel Loaded Targeted Polymeric Micelles in Tumor Bearing Mice. AB - A simple, rapid, and sensitive reversed-phase HPLC method was developed and validated for determination of paclitaxel (PTX) in plasma, various organs and tumor tissues of tumor-bearing mice. Tissue specimens of liver, kidneys, spleen, lungs, heart and tumor were separately homogenized in normal saline. Plasma or tissue homogenate (250 ul) containing PTX and internal standard (diazepam) were extracted by diethyl ether (6 ml). The separation was achieved on a u-Bondapak C18 HPLC column using sodium acetate buffer solution (0.01 M)/acetonitrile (58/42 v/v) at pH 5 +/- 0.1 and flow rate of 1.9 mL/min. The effluent was monitored at 227 nm and column temperature was adjusted at 58oC. The internal standard and PTX were eluted at 4.2 and 5.2 min, respectively and no interfering peaks were observed. Calibration curves were linear over the concentration range of 0.25-10 ug/ml of PTX in plasma and 0.3-20 ug/ml PTX in tissue homogenates with acceptable precision and accuracy (<15%). The mean recoveries of the drug after plasma extraction was 87.4% +/- 3.6 while those of tissue homogenates ranged from 62.1+/ 4.5 to 75.5+/- 3.2 depending on the type of tissues studied. PTX was stable in samples with no evidence of degradation during 3 freeze-thaw cycles and 3 months storage at -70 degrees C. The developed HPLC method was applied to quantify PTX in the mouse plasma and tissues after intravenous administration of 10 mg equivalent PTX/Kg dose of PTX-loaded tocopherol succinate-chitosan-polyethylene glycol-folate (TS-CS-PEG-FA) micelles formulation or Anzatax(r) (Cremophor(r) EL- based formulation of PTX) to female Balb/c mice. PMID- 26670365 TI - Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses. AB - PURPOSE: Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems. PMID- 26670367 TI - Effects of Prescription Drug Reduction on Quality of Life in Community-Dwelling Patients with Dementia. AB - PURPOSE: Due to the use of multiple drugs and prevalence of diminished cognitive function, community-dwelling elderly individuals are more likely to have drug related issues. We examined changes in quality of life (QOL) and activities of daily living (ADL) 3 months and 6 months after reducing drug use of dementia patients who had newly begun community-dwelling care. METHODS: Prescription drug use was reduced in the intervention group, whereas the non-intervention group continued their regimen or began using additional drugs. QOL and ADL were assessed with the Japanese version of the EQ-5D and the Barthel Index, respectively. RESULTS: Subjects were 32 individuals aged >=65 years who had begun community-dwelling between March and July 2014 and had received approval for long term care insurance. On average, the intervention group (n = 19) stopped using 2.6 prescription drugs. After 6 months, the differences in the QOL and ADL scores in the intervention group were -0.03 +/- 0.29 and 6.32 +/- 18.6, respectively, while the differences in the QOL and ADL scores in the non-intervention group (n = 13) were -0.13 +/- 0.29 and -2.69 +/- 23.7, respectively. In the intervention group, ADL scores were significantly increased by 14.0 +/- 11.1 6 months after reduced benzodiazepine use. CONCLUSIONS: QOL was maintained with reduced drug use, while ADL score was slightly increased. In addition, the reduction of benzodiazepine use significantly increased ADL. In order to reduce polypharmacy among community-dwelling elderly patients, it is necessary to create an opportunity for pharmacists to re-examine their prescriptions. PMID- 26670366 TI - In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction. AB - PURPOSE: The ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO)] (DCBPY) is a nitric oxide (NO) donor and studies suggested that the ruthenium compounds can inactivate O2-. The aim of this study is to test if DCBPY can revert and/or prevent the endothelial dysfunction. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. To vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: DCBPY: 0.1; 1 and 10MUM, DCBPY plus hydroxocobalin (NO scavenger) or tempol during 30 minutes, and concentration effect curves to acetylcholine were performed. The potency values (pD2) and maximum effect (ME) were analyzed. The O2- was generated using hypoxantine xantine oxidase and the reduction of cytochrome c, NO consumption by O2- and the effect in avoid NO consumption was measured. RESULTS: In 2K-1C DCBPY at 0.1; 1 or 10MUM improved the relaxation endothelium dependent induced by acetylcholine in aortic rings compared to control 2K-1C, and also improved ME. In rings from 2K incubation with DCBPY (0.1; 1.0 and 10 MUM) did not change pD2 or ME. Incubation with 0.1 MUM of DCBPY plus hydroxocobalamin did not modify the potency and ME in 2K-1C compared to DCBPY (0.1 MUM). DCBPY and SOD inhibits the reduction of cytochrome c and inhibited the NO consumption by O2-, showing that O2- has been removed from the solution. CONCLUSION: Our results suggest that DCBPY at a lower concentration (0.1 uM) is not an NO generator, but can inactivate superoxide and improves the endothelial function. PMID- 26670368 TI - Supercritical Fluid Technologies to Fabricate Proliposomes. AB - Proliposomes are stable drug carrier systems designed to form liposomes upon addition of an aqueous phase. In this review, current trends in the use of supercritical fluid (SCF) technologies to prepare proliposomes are discussed. SCF methods are used in pharmaceutical research and industry to address limitations associated with conventional methods of pro/liposome fabrication. The SCF solvent methods of proliposome preparation are eco-friendly (known as green technology) and, along with the SCF anti-solvent methods, could be advantageous over conventional methods; enabling better design of particle morphology (size and shape). The major hurdles of SCF methods include poor scalability to industrial manufacturing which may result in variable particle characteristics. In the case of SCF anti-solvent methods, another hurdle is the reliance on organic solvents. However, the amount of solvent required is typically less than that used by the conventional methods. Another hurdle is that most of the SCF methods used have complicated manufacturing processes, although once the setup has been completed, SCF technologies offer a single-step process in the preparation of proliposomes compared to the multiple steps required by many other methods. Furthermore, there is limited research into how proliposomes will be converted into liposomes for the end-user, and how such a product can be prepared reproducibly in terms of vesicle size and drug loading. These hurdles must be overcome and with more research, SCF methods, especially where the SCF acts as a solvent, have the potential to offer a strong alternative to the conventional methods to prepare proliposomes. PMID- 26670369 TI - Pravastatin Modulate Niemann-Pick C1-Like 1 and ATP-Binding Cassette G5 and G8 to Influence Intestinal Cholesterol Absorption. AB - PURPOSE: Niemann-Pick C1-like 1 (NPC1L1), ATP-binding cassette (ABC)G5, and ABCG8 mediate intestinal cholesterol absorption. It is unclear whether pravastatin (PR) or ezetimibe (EZ) affect expression of these transporters. We examined the effects of PR and EZ on NPC1L1, ABCG5, and ABCG8 expression in human hepatoma HepG2 cells and the murine small intestine. We also assessed expression of the transcription factors liver X receptor (LXR)a, LXRb and sterol regulatory element binding protein. METHODS: Transporter mRNA levels were determined in murine small intestines 6 and 24 h after oral PR and EZ administration by real-time reverse transcriptase polymerase chain reaction (RT-PCR). In PR- and EZ-treated HepG2 cells, transporter and transcription factor mRNA and protein levels were examined by RT-PCR and western blot, respectively. RESULTS: Significant decreases in NPC1L1, ABCG5, and ABCG8 mRNA expression were observed in the duodenum, but not jejunum and ileum, of mice 24 h after treatment with PR, but not EZ. In HepG2 cells, PR but not EZ treatment for 24 h also significantly decreased NPC1L1 protein and ABCG5, and ABCG8 mRNA expression, while increasing LXRa mRNA levels. CONCLUSION: PR but not EZ treatment reduced duodenal cholesterol transporter expression in mice. PR-induced increases in LXRa mRNA levels may be involved in attenuation of NPC1L1 expression, subsequently decreasing intestinal cholesterol absorption. PMID- 26670370 TI - When Bioequivalence in Healthy Volunteers May not Translate to Bioequivalence in Patients: Differential Effects of Increased Gastric pH on the Pharmacokinetics of Levothyroxine Capsules and Tablets. AB - PURPOSE: Clinical studies have suggested that proton pump inhibitors may decrease levothyroxine absorption and an in vitro study suggested that the effect of pH on dissolution may differ with formulation. To determine the impact of formulation on the pharmacokinetics of levothyroxine in altered gastric pH conditions, this study compared the pharmacokinetics of levothyroxine capsules and tablets, two formulations deemed bioequivalent in healthy volunteers under fasting conditions, when taken with or without esomeprazole. METHODS: Two clinical studies were conducted in healthy volunteers given single dose levothyroxine (600 mg) with a 45-day washout period. In Study 1 (parallel-design/two-way crossover), 16 subjects received either levothyroxine capsules or tablets, each group with or without prior administration of intravenous esomeprazole (maximum dose of 80 mg). In Study 2 (two-way crossover), 16 subjects received both capsules or tablets after intravenous esomeprazole. Blood samples were collected pre-dose and up to 24 hours post-dose. Baseline-adjusted pharmacokinetic parameters were calculated: Cmax (maximal concentration), Tmax (time to Cmax), AUC0-t (area under the concentration-time curve from 0 to the last detectable concentration), AUC0-6 and AUC0-12 (areas under the curve from 0 to 6 and 12 hours, respectively). Analyses of variance were conducted to compare ln-transformed Cmax and AUC. Non-parametric Tmax analyses were done. RESULTS: In Study 1, esomeprazole caused a greater decrease in overall levothyroxine exposure of tablets vs. capsules (13% vs 6% for Cmax, 18% vs. 14% for AUC(0-6), 17% vs. 5% for AUC(0-12) and 10% vs. 8% for AUC(0 t)). In Study 2 esomeprazole administration resulted in a 16% smaller levothyroxine exposure with tablets vs. capsules. No statistically significant differences in Tmax were found. CONCLUSIONS: Although both formulations are considered "bioequivalent" in healthy volunteers, they may not necessarily be bioequivalent in patients with impaired gastric pH conditions. Levothyroxine capsules may therefore be more appropriate for patients with decreased gastric acidity. PMID- 26670371 TI - Application of Counter-propagation Artificial Neural Networks in Prediction of Topiramate Concentration in Patients with Epilepsy. AB - PURPOSE: The application of artificial neural networks in the pharmaceutical sciences is broad, ranging from drug discovery to clinical pharmacy. In this study, we explored the applicability of counter-propagation artificial neural networks (CPANNs), combined with genetic algorithm (GA) for prediction of topiramate (TPM) serum levels based on identified factors important for its prediction. METHODS: The study was performed on 118 TPM measurements obtained from 78 adult epileptic patients. Patients were on stable TPM dosing regimen for at least 7 days; therefore, steady-state was assumed. TPM serum concentration was determined by high performance liquid chromatography with fluorescence detection. The influence of demographic, biochemical parameters and therapy characteristics of the patients on TPM levels were tested. Data analysis was performed by CPANNs. GA was used for optimal CPANN parameters, variable selection and adjustment of relative importance. RESULTS: Data for training included 88 measured TPM concentrations, while remaining were used for validation. Among all factors tested, TPM dose, renal function (eGFR) and carbamazepine dose significantly influenced TPM level and their relative importance were 0.7500, 0.2813, 0.0625, respectively. Relative error and root mean squared relative error (%) and their corresponding 95% confidence intervals for training set were 2.14 [(-2.41) - 6.70] and 21.5 [18.5 - 24.1]; and for test set were -6.21 [(-21.2) - 8.77] and 39.9 [31.7 - 46.7], respectively. CONCLUSIONS: Statistical parameters showed acceptable predictive performance. Results indicate the feasibility of CPANNs combined with GA to predict TPM concentrations and to adjust relative importance of identified variability factors in population of adult epileptic patients. PMID- 26670372 TI - Professional Pharmacy Services and Patient Complexity: An Observational Study. AB - PURPOSE: To examine the association between the provision of professional pharmacy services (PPS) and patient complexity as determined by the number of distinct medications dispensed in Ontario. METHODS: We conducted a cross sectional study among all individuals dispensed one or more medications under the Ontario Public Drug Program (OPDP) between April 1st, 2012 and March 31st, 2013. We compared characteristics of patients receiving -1 or more PPS to those receiving no PPS. To assess the relationship between patient complexity (as measured by the number of chronic medications dispensed) and receipt of PPS, we reported the number and proportion of patients eligible for Ontario Drug Benefits (ODB) who received a PPS within each patient complexity group, and compared these proportions using the Cochran-Armitage test. RESULTS: Over the 1-year study period, 27.1% (N = 799,674 of 2,946,183) of ODB beneficiaries received at least one professional pharmacy service. Among these services, more than two-thirds of the patients received a MedsCheck service (N=511,490; 64.0%). Overall, individuals who received a PPS tended to be older, more likely to reside in a long-term care (LTC) facility, have multiple comorbidities, and were more likely to have been prescribed 9 or more medications in the past year. As patient complexity increased, the proportion of ODB beneficiaries who received PPS also increased; 3.0% of individuals prescribed between 1 and 2 medications in the past year received PPS, while 53.6% of those treated with 13 or more medications received PPS (p<0.0001). CONCLUSIONS: Although the findings of our study suggest the use of PPS increases with patient complexity, many complex patients are not receiving these services. Further studies are required to better understand why patients do not access these services, the impact of professional pharmacy services on patient health outcomes, and their value for the health care system. PMID- 26670373 TI - Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine. AB - PURPOSE: Adenosine plays an important role in the pathogenesis of homocysteine associated vascular complications. METHODS: This study examined the effects of dipyridamole, an inhibitor for nucleoside transport, on impaired angiogenic processes caused by homocysteine and adenosine in human cardiovascular endothelial cell line (EAhy926). RESULTS: The results showed that dipyridamole restored the extracellular adenosine and intracellular S-adenosylhomocysteine concentrations disrupted by the combination of homocysteine and adenosine. Dipyridamole also ameliorated the impaired proliferation, migration and formation of capillary-like tubes of EAhy926 cells caused by the combination of homocysteine and adenosine. Mechanism analysis revealed that dipyridamole induced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinases (ERK) and its effect on cell growth was attenuated by the MEK inhibitor, U0126. CONCLUSION: Dipyridamole protected against impaired angiogenesis caused by homocysteine and adenosine, at least in part, by activating the MEK/ERK signalling pathway, and this could be associated with its effects in suppressing intracellular S-adenosylhomocysteine accumulation. NOVELTY OF THE WORK: This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine. PMID- 26670374 TI - Pathogenesis of Pregabalin-Induced Limb Defects in Mouse Embryos. AB - PURPOSE: It is known that antiepileptic drugs might adversely affect neuronal function and thus influence brain development. However, we have reported that limb deformities are one of the most prominent disturbances caused by pregabalin (PGB) in the developing embryo. The aim of this work is to gain a better understanding of possible molecular mechanisms behind the musculoskeletal injuries and limb deformities associated with PGB. METHODS: Pregnant mice divided into four groups. Each mouse received an intraperitoneal injection (IP) of 0, 20 (group I), 40 (group II) or 80 (group III) mg/kg/day of PGB during the organogenesis period. On gestational day 18, embryos were separated and their limbs were dissected. Levels of apoptotic proteins were analyzed by Western blotting. To establish whether apoptosis is present in the limbs, the specimens were examined by TUNEL. Pathological findings were also reported as a score ranging from 1 to 3 based on the level of differentiation. RESULTS: Western blot analysis demonstrated that PGB in all PGB-treated groups significantly upregulated the levels of cleaved caspase-3, 8 and 9. Also, the results showed that PGB exposure increased the percentage of TUNEL positive cells in different limb tissues especially the mesenchymal tissue. The histopathological findings revealed that PGB administration to pregnant mice inhibited limb tissue differentiation, albeit to varying degrees. CONCLUSIONS: The result of our study revealed that apoptosis and inhibition of limb tissue differentiation play an important role in the pathogenesis of PGB-induced limb malformations. Both intrinsic and extrinsic caspase-dependent pathways of cell death are important in mediating the abnormal limb development triggered by insult with the PGB. Evaluating the effect of PGB on molecules involved in the cross-talk between intrinsic and extrinsic apoptotic pathways and cell adhesion, migration, proliferation, and differentiation during embryonic development can further help to identify and clarify the involved mechanisms. PMID- 26670375 TI - Spirit Guide. PMID- 26670376 TI - Detecting number processing and mental calculation in patients with disorders of consciousness using a hybrid brain-computer interface system. AB - BACKGROUND: For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients' motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication. METHODS: In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n = 6) or in a minimally conscious state (n = 3) or who emerged from a minimally conscious state (n = 2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback. RESULTS: Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients. CONCLUSIONS: Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses. PMID- 26670378 TI - Stretchable, Transparent Electrodes as Wearable Heaters Using Nanotrough Networks of Metallic Glasses with Superior Mechanical Properties and Thermal Stability. AB - Mechanical robustness, electrical and chemical reliabilities of devices against large deformations such as bending and stretching have become the key metrics for rapidly emerging wearable electronics. Metallic glasses (MGs) have high elastic limit, electrical conductivity, and corrosion resistance, which can be promising for applications in wearable electronics. However, their applications in wearable electronics or transparent electrodes have not been extensively explored so far. Here, we demonstrate stretchable and transparent electrodes using CuZr MGs in the form of nanotrough networks. MG nanotroughs are prepared by electrospinning and cosputtering process, and they can be transferred to various desired substrates, including stretchable elastomeric substrates. The resulting MG nanotrough network is first utilized as a stretchable transparent electrode, presenting outstanding optoelectronic (sheet resistance of 3.8 Omega/sq at transmittance of 90%) and mechanical robustness (resistance change less than 30% up to a tensile strain of 70%) as well as excellent chemical stability against hot and humid environments (negligible degradation in performance for 240 h in 85% relative humidity and 85 degrees C). A stretchable and transparent heater based on the MG nanotrough network is also demonstrated with a wide operating temperature range (up to 180 degrees C) and excellent stretchability (up to 70% in the strain). The excellent mechanical robustness of these stretchable transparent electrode and heater is ascribed to the structural configuration (i.e., a nanotrough network) and inherent high elastic limit of MGs, as supported by experimental results and numerical analysis. We demonstrate their real-time operations on human skin as a wearable, transparent thermotherapy patch controlled wirelessly using a smartphone as well as a transparent defroster for an automobile side-view mirror, suggesting a promising strategy toward next-generation wearable electronics or automobile applications. PMID- 26670377 TI - 3,4-methylenedioxymethamphetamine increases excitability in the dentate gyrus: role of 5HT2A receptor-induced PGE2 signaling. AB - 3,4-methylenedioxymethamphetamine (MDMA) is a widely abused psychostimulant, which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid induced seizures in MDMA-treated rats, which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats. We hypothesized that the widely abused psychostimulant MDMA causes a loss of parvalbumin (PV) cells and increases excitability in the dentate gyrus. MDMA increases serotonin (5HT) release and activates 5HT2A receptors. The increased activation of 5HT2A receptors promotes the production of prostaglandin E2 (PGE2) and subsequent activation of EP1 receptors in the dentate gyrus. EP1 receptor activation leads to eventual excitotoxicity and loss of PV interneurons resulting in reduced inhibition and lowered seizure threshold resulting in increased seizure susceptibility. PMID- 26670379 TI - Patterns and Mechanisms of Artificial Kidney Failure during Continuous Renal Replacement Therapy. AB - BACKGROUND: We aimed to describe the previously unstudied relationship between circuit pressures and circuit clotting, here labeled as 'artificial kidney failure' (AKF), in patients receiving continuous renal replacement therapy (CRRT). METHODS: We performed an observational study of CRRT-treated critically ill patients to continuously record the multiple CRRT circuit pressures. RESULTS: Three patterns of access outflow dysfunction (AOD) were also noted: severe, moderate and mild. Compared with circuits without AOD, circuits experiencing at least one AOD episode had shorter lifespans (14.2 +/- 12.7 vs. 21.3 +/- 16.5 h, p = 0.057). This effect was more obvious with moderate or severe AOD (8.7 +/- 4.6 vs. 20.6 +/- 15.7 h, p = 0.007). If any AOD events occurred within the first 4 h, the sensitivity and specificity in predicting early-immediate AKF were 53.4 and 94.4%, respectively. CONCLUSIONS: Early and intermediate AKF during CRRT is most likely dependent on AOD, which is a frequent event with variable severity. PMID- 26670380 TI - [The Risks of Perioperative Addiction to Benzodiazepines in the Elderly: What the Surgeon Needs to Know]. AB - BACKGROUND: In Germany, more than one million people use benzodiazepines on a regular basis. The majority of them is older than 60 years and take low-dose benzodiazepines for sleep disorders. This does not necessarily induce tolerance, but may result in problems such as falling, seizures or delirium if benzodiazepines are discontinued or taken on a long-term basis. Therefore, benzodiazepines can be associated with problems before, during and after surgery, in particular in the elderly. This narrative review aims to describe the clinical relevance for daily practice. KEY POINTS: 1. The high-dose use of drugs that induce addiction with possible parallel consumption of other drugs is clinically important. Even more relevant, however, is the large number of elderly people taking benzodiazepines periodically and in low doses for sleep disturbances. 2. Low-dose addiction of benzodiazepines is defined as daily use of less than 20 mg of a diazepam equivalent. 3. Short-acting benzodiazepines can promote addiction; long-acting benzodiazepines produce hangover effects. 4. During a hospital stay, rapid discontinuation induces withdrawal symptoms; continuous prescription may result in incidents and increases the risk of postoperative delirium. CONCLUSION: For the intake and continuous prescription there are four basic rules:Well defined indication, correct dosage, short application, no sudden discontinuation. PMID- 26670382 TI - Weakly Deleterious Mutations and Low Rates of Recombination Limit the Impact of Natural Selection on Bacterial Genomes. AB - Free-living bacteria are usually thought to have large effective population sizes, and so tiny selective differences can drive their evolution. However, because recombination is infrequent, "background selection" against slightly deleterious alleles should reduce the effective population size (Ne) by orders of magnitude. For example, for a well-mixed population with 10(12) individuals and a typical level of homologous recombination (r/m = 3, i.e., nucleotide changes due to recombination [r] occur at 3 times the mutation rate [m]), we predict that Ne is <10(7). An argument for high Ne values for bacteria has been the high genetic diversity within many bacterial "species," but this diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimate Ne correctly. Given an estimate of Ne, standard population genetics models imply that selection should be sufficient to drive evolution if Ne * s is >1, where s is the selection coefficient. We found that this remains approximately correct if background selection is occurring or when population structure is present. Overall, we predict that even for free-living bacteria with enormous populations, natural selection is only a significant force if s is above 10(-7) or so. IMPORTANCE: Because bacteria form huge populations with trillions of individuals, the simplest theoretical prediction is that the better allele at a site would predominate even if its advantage was just 10(-9) per generation. In other words, virtually every nucleotide would be at the local optimum in most individuals. A more sophisticated theory considers that bacterial genomes have millions of sites each and selection events on these many sites could interfere with each other, so that only larger effects would be important. However, bacteria can exchange genetic material, and in principle, this exchange could eliminate the interference between the evolution of the sites. We used simulations to confirm that during multisite evolution with realistic levels of recombination, only larger effects are important. We propose that advantages of less than 10(-7) are effectively neutral. PMID- 26670381 TI - Free mate choice enhances conservation breeding in the endangered giant panda. AB - Conservation breeding programmes have become an increasingly important tool to save endangered species, yet despite the allocation of significant resources, efforts to create self-sustaining populations have met with limited success. The iconic giant panda (Ailuropoda melanoleuca) embodies the struggles associated with ex situ species conservation. Here we show that behavioural mate preferences in giant pandas predict reproductive outcomes. Giant pandas paired with preferred partners have significantly higher copulation and birth rates. Reproductive rates increase further when both partners show mutual preference for one another. If managers were to incorporate mate preferences more fully into breeding management, the production of giant panda offspring for China's reintroduction programme might be greatly expedited. When extended to the increasing numbers of species dependent on ex situ conservation breeding to avoid extinction, our findings highlight that mate preference and other aspects of informed behavioural management could make the difference between success and failure of these programmes. PMID- 26670383 TI - Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri. AB - Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1beta in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. IMPORTANCE: Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics. PMID- 26670384 TI - Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas. AB - Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes--MYC, MYB, Mir-155, and TERT--have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high throughput sequencing to identify additional genes driving tumorigenesis in ALV induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including TNFRSF1A, MEF2C, CTDSPL, TAB2, RUNX1, MLL5, CXorf57, and BACH2. We also analyze the genome-wide ALV integration landscape in vivo and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration in vivo in the chicken genome. IMPORTANCE: Avian leukosis virus induces B-cell lymphomas in chickens. Earlier studies showed that ALV can induce tumors through insertional mutagenesis, and several genes have been implicated in the development of these tumors. In this study, we use high-throughput sequencing to reveal the genome wide ALV integration landscape in ALV-induced B-cell lymphomas. We find elevated levels of ALV integration near transcription start sites and use common integration site analysis to greatly expand the number of genes implicated in the development of these tumors. Interestingly, we identify several genes targeted by viral insertions that have not been previously shown to be involved in cancer. PMID- 26670385 TI - Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons. AB - Iron, a major protein cofactor, is essential for most organisms. Despite the well known effects of O2 on the oxidation state and solubility of iron, the impact of O2 on cellular iron homeostasis is not well understood. Here we report that in Escherichia coli K-12, the lack of O2 dramatically changes expression of genes controlled by the global regulators of iron homeostasis, the transcription factor Fur and the small RNA RyhB. Using chromatin immunoprecipitation sequencing (ChIP seq), we found anaerobic conditions promote Fur binding to more locations across the genome. However, by expression profiling, we discovered that the major effect of anaerobiosis was to increase the magnitude of Fur regulation, leading to increased expression of iron storage proteins and decreased expression of most iron uptake pathways and several Mn-binding proteins. This change in the pattern of gene expression also correlated with an unanticipated decrease in Mn in anaerobic cells. Changes in the genes posttranscriptionally regulated by RyhB under aerobic and anaerobic conditions could be attributed to O2-dependent changes in transcription of the target genes: aerobic RyhB targets were enriched in iron-containing proteins associated with aerobic energy metabolism, whereas anaerobic RyhB targets were enriched in iron-containing anaerobic respiratory functions. Overall, these studies showed that anaerobiosis has a larger impact on iron homeostasis than previously anticipated, both by expanding the number of direct Fur target genes and the magnitude of their regulation and by altering the expression of genes predicted to be posttranscriptionally regulated by the small RNA RyhB under iron-limiting conditions. IMPORTANCE: Microbes and host cells engage in an "arms race" for iron, an essential nutrient that is often scarce in the environment. Studies of iron homeostasis have been key to understanding the control of iron acquisition and the downstream pathways that enable microbes to compete for this valuable resource. Here we report that O2 availability affects the gene expression programs of two Escherichia coli master regulators that function in iron homeostasis: the transcription factor Fur and the small RNA regulator RyhB. Fur appeared to be more active under anaerobic conditions, suggesting a change in the set point for iron homeostasis. RyhB preferentially targeted iron-containing proteins of respiration-linked pathways, which are differentially expressed under aerobic and anaerobic conditions. Such findings may be relevant to the success of bacteria within their hosts since zones of reduced O2 may actually reduce bacterial iron demands, making it easier to win the arms race for iron. PMID- 26670386 TI - Suppression of Drug Resistance in Dengue Virus. AB - Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug resistant virus correlated with cooligomerization of the targeted drug susceptible and drug-resistant core proteins. The concept of "dominant drug targets," in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection. IMPORTANCE: Drug resistance is a major hurdle in the development of effective antivirals, especially those directed at RNA viruses. We have found that one can use the concept of the genetic dominance of defective subunits to "turn cousins into enemies," i.e., to thwart the outgrowth of drug-resistant viral genomes as soon as they are generated. This requires deliberate targeting of larger assemblages, which would otherwise rarely be considered by antiviral researchers. PMID- 26670387 TI - Contribution of Physical Interactions to Signaling Specificity between a Diguanylate Cyclase and Its Effector. AB - Cyclic diguanylate (c-di-GMP) is a bacterial second messenger that controls multiple cellular processes. c-di-GMP networks have up to dozens of diguanylate cyclases (DGCs) that synthesize c-di-GMP along with many c-di-GMP-responsive target proteins that can bind and respond to this signal. For such networks to have order, a mechanism(s) likely exists that allow DGCs to specifically signal their targets, and it has been suggested that physical interactions might provide such specificity. Our results show a DGC from Pseudomonas fluorescens physically interacting with its target protein at a conserved interface, and this interface can be predictive of DGC-target protein interactions. Furthermore, we demonstrate that physical interaction is necessary for the DGC to maximally signal its target. If such "local signaling" is a theme for even a fraction of the DGCs used by bacteria, it becomes possible to posit a model whereby physical interaction allows a DGC to directly signal its target protein, which in turn may help curtail undesired cross talk with other members of the network. IMPORTANCE: An important question in microbiology is how bacteria make decisions using a signaling network made up of proteins that make, break, and bind the second messenger c-di-GMP, which is responsible for controlling many cellular behaviors. Previous work has shown that a given DGC enzyme will signal for specific cellular outputs, despite making the same diffusible molecule as its sibling DGCs in the unpartitioned space of the bacterial cell. Understanding how one DGC differentiates its output from the dozens of other such enzymes in the cell is synonymous with understanding a large component of the bacterial decision-making machinery. We present evidence for a helix on a DGC used to physically associate with its target protein, which is necessary to achieve maximal signaling. PMID- 26670388 TI - Design and analysis of trials with a partially nested design and a binary outcome measure. AB - Where treatments are administered to groups of patients or delivered by therapists, outcomes for patients in the same group or treated by the same therapist may be more similar, leading to clustering. Trials of such treatments should take account of this effect. Where such a treatment is compared with an un clustered treatment, the trial has a partially nested design. This paper compares statistical methods for this design where the outcome is binary. Investigation of consistency reveals that a random coefficient model with a random effect for group or therapist is not consistent with other methods for a null treatment effect, and so this model is not recommended for this design. Small sample performance of a cluster-adjusted test of proportions, a summary measures test and logistic generalised estimating equations and random intercept models are investigated through simulation. The expected treatment effect is biased for the logistic models. Empirical test size of two-sided tests is raised only slightly, but there are substantial biases for one-sided tests. Three formulae are proposed for calculating sample size and power based on (i) the difference of proportions, (ii) the log-odds ratio or (iii) the arc-sine transformation of proportions. Calculated power from these formulae is compared with empirical power from a simulations study. Logistic models appeared to perform better than those based on proportions with the likelihood ratio test performing best in the range of scenarios considered. For these analyses, the log-odds ratio method of calculation of power gave an approximate lower limit for empirical power. PMID- 26670390 TI - Celebrating 50 Years of Publication! PMID- 26670391 TI - Quadruplex DNA-Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers. AB - Four dinuclear terpyridineplatinum(II) (Pt-terpy) complexes were investigated for interactions with G-quadruplex DNA (QDNA) and duplex DNA (dsDNA) by synchrotron radiation circular dichroism (SRCD), fluorescent intercalator displacement (FID) assays and fluorescence resonance energy transfer (FRET) melting studies. Additionally, computational docking studies were undertaken to provide insight into potential binding modes for these complexes. The complexes demonstrated the ability to increase the melting temperature of various QDNA motifs by up to 17 degrees C and maintain this in up to a 600-fold excess of dsDNA. This study demonstrates that dinuclear Pt-terpy complexes stabilise QDNA and have a high degree of selectivity for QDNA over dsDNA. PMID- 26670392 TI - Torque teno virus: a ubiquitous virus. PMID- 26670393 TI - Red blood cell storage and alloimmunization: a fact or a myth? PMID- 26670394 TI - Haptoglobin: an emerging candidate for phenotypic modulation of sickle cell anemia? PMID- 26670395 TI - Comment on sickle cell disease and left ventricular hypertrophy. PMID- 26670396 TI - Qualitative polymerase chain reaction versus quantitative polymerase chain reaction for the detection of minimal residual disease in children with acute lymphoblastic leukemia. PMID- 26670397 TI - Scientific comment on health-related quality of life among blood donors with hepatitis B and hepatitis C: longitudinal study before and after diagnosis? PMID- 26670398 TI - Clostridium difficile infection is a frequent but well-controlled event after hematopoietic cell transplantation. PMID- 26670389 TI - In vivo experience with natural scaffolds for myocardial infarction: the times they are a-changin'. AB - Treating a myocardial infarction (MI), the most frequent cause of death worldwide, remains one of the most exciting medical challenges in the 21st century. Cardiac tissue engineering, a novel emerging treatment, involves the use of therapeutic cells supported by a scaffold for regenerating the infarcted area. It is essential to select the appropriate scaffold material; the ideal one should provide a suitable cellular microenvironment, mimic the native myocardium, and allow mechanical and electrical coupling with host tissues. Among available scaffold materials, natural scaffolds are preferable for achieving these purposes because they possess myocardial extracellular matrix properties and structures. Here, we review several natural scaffolds for applications in MI management, with a focus on pre-clinical studies and clinical trials performed to date. We also evaluate scaffolds combined with different cell types and proteins for their ability to promote improved heart function, contractility and neovascularization, and attenuate adverse ventricular remodeling. Although further refinement is necessary in the coming years, promising results indicate that natural scaffolds may be a valuable translational therapeutic option with clinical impact in MI repair. PMID- 26670399 TI - Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia. AB - INTRODUCTION: Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. OBJECTIVE: The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. METHODS: Seventy four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan-Meier and multivariate Cox methods and the log rank test were used for statistical analysis. RESULTS: Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1*10(-3) for precursor B-cell acute lymphoblastic leukemia and 1*10(-2) for T cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1%+/-5.6% versus 41.7%+/-17.3%, respectively; p-value=0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. CONCLUSION: Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. PMID- 26670400 TI - Health-related quality of life among blood donors with hepatitis B and hepatitis C: longitudinal study before and after diagnosis. AB - INTRODUCTION: There is evidence that patients suffering from chronic hepatic diseases, including chronic hepatitis B and chronic hepatitis C, have a reduced health-related quality of life. The aim of this study was to evaluate the impact of the notification of test results for hepatitis B and hepatitis C on the quality of life of blood donors. METHODS: Over a 29-month period, this study assessed the quality of life of 105 blood donors with positive serological screening tests for hepatitis B and hepatitis C and donors who presented false positive test results. The Medical Outcome Study 36-Item Short Form Health Survey Questionnaire was applied at three time points: (1) when an additional blood sample was collected for confirmatory tests; (2) when donors were notified about their serological status; and (3) when donors, positive for hepatitis B and hepatitis C, started clinical follow-up. Quality of life scores for the confirmed hepatitis B and hepatitis C groups were compared to the false-positive control group. RESULTS: The domains bodily pain, general health perception, social function, and mental health and the physical component improved significantly in donors with hepatitis C from Time Point 1 to Time Point 3. Health-related quality of life scores of donors diagnosed with hepatitis B and hepatitis C were significantly lower in six and four of the eight domains, respectively, compared to the false-positive control group. CONCLUSION: A decreased quality of life was detected before and after diagnosis in blood donors with hepatitis B and hepatitis C. Contrary to hepatitis B positive donors, the possibility of medical care may have improved the quality of life among hepatitis C positive donors. PMID- 26670401 TI - Clostridium difficile infection in Chilean patients submitted to hematopoietic stem cell transplantation. AB - INTRODUCTION: Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identified. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. METHODS: A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. RESULTS: Two hundred and fifty patients were studied (mean age: 39 years; range: 17-69), with 147 (59%) receiving allogeneic transplants and 103 (41%) receiving autologous transplants. One hundred and ninety-two (77%) patients had diarrhea, with 25 (10%) cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic transplants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia). In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value=0.56). Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value=0.008). In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p-value=0.71). In the allogeneic transplant group, the median time to acute graft-versus-host disease was similar between the two groups (p-value=0.08), as was the incidence of grades 1-4 acute graft-versus-host disease (40% vs. 48%; p-value >0.05). CONCLUSION: The incidence of C. difficile infection after hematopoietic stem cell transplantation was low, with a significant number of cases occurring shortly after transplantation. Allogeneic transplants had a three-time higher risk of infection compared to autologous transplants, but this was not associated with increased mortality, decreased overall survival or higher risk of acute graft versus-host disease. PMID- 26670402 TI - Could CD64 expression be used as a predictor of positive culture results in children with febrile neutropenia? AB - BACKGROUND: Early recognition of infectious processes in neutropenic patients is hampered by the fact that these processes may have dissimilar and non-specific clinical presentations. CD64 is a neutrophil surface marker that is not expressed in non-sensitized neutrophils. When the neutrophil is exposed to tumor necrosis factor-alpha it is activated and is measured via the CD64 index. METHODS: This paper evaluated the relationship between the index value of CD64 on the first day of febrile neutropenia and a positive blood culture. The correlations with white blood count, C-reactive protein and erythrocyte sedimentation rate were also evaluated. This case-control, prospective, diagnostic study included 64 episodes of neutropenia. Case group (n=14) comprised positive blood cultures, and the control group (n=50), negative blood cultures. RESULTS: The median rates of CD64 were 2.1 (sigma+/-3.9) in the case group and 1.76 (sigma+/-5.02) in the control group. There was no correlation between the value of the CD64 index and blood cultures. The CD64 index was also not correlated with C-reactive protein positivity. Furthermore, the CD64 index was not able to predict blood culture positivity. The sensitivity was 64.3%, the specificity was 42%, the positive predictive value was 23.7% and the negative predictive value was 80%. For C reactive protein, the sensitivity, specificity, positive predictive value, and negative predictive value were 71.4%, 32%, 22.7%, and 80%, respectively. CONCLUSION: The CD64 index is not suitable for predicting the positivity of blood cultures in this specific population of patients with febrile neutropenia. PMID- 26670403 TI - Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia. AB - Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID- 26670404 TI - Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia. AB - Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil. PMID- 26670405 TI - Spurious laboratory alterations in pernicious anemia. PMID- 26670406 TI - Axillary high-grade B-cell non-Hodgkin lymphoma presenting under the guise of inflammatory breast carcinoma. PMID- 26670407 TI - Van den Berghe's 5q- syndrome and myelodysplastic syndrome with isolated del(5q). PMID- 26670408 TI - Diagnostic approach to hemolytic anemias in the adult. PMID- 26670409 TI - Graphene-Wrapped Na2C12H6O4 Nanoflowers as High Performance Anodes for Sodium-Ion Batteries. AB - Graphene-wrapped organic nanoflowers are synthesized from ultrasonic treatment of a simple microsized disodium salt (Na212H6O4) and graphene, which demonstrates a greatly enhanced electrochemical capacity, rate capability and cycling stability as organic Na(+) storage anode. This work suggests an effective architecture to make organic materials electrochemically energetic and stable for energy storage applications. PMID- 26670410 TI - Computed Tomographic presentation of obstructive jejunal adenocarcinoma associated with celiac disease and incomplete intestinal malrotation. AB - INTRODUCTION: Small bowel adenocarcinoma is a rare entity most frequently observed with celiac disease. This is the first case report on the association of celiac disease, small bowel adenocarcinoma and intestinal malrotation. CASE REPORT: A 40 year-old male patient diagnosed with celiac disease since the age of 5 years complained of epigastric pain and vomiting for three days. Computed tomography (CT) showed a significant gastroduodenal dilatation with thickened intestinal wall proximal to the duodenojejunal flexure. The lumen contained a food bezoar in the center. The duodenojejunal angle was abnormally on the right side of the abdomen and the superior mesenteric vein was anterior to the superior mesenteric artery. Endoscopy after aspiration found a hemi-circumferential and irregular mass which bled at the contact of fibroscope. Biopsies showed an adenocarcinoma and small bowel resection was performed. DISCUSSION: Celiac disease is associated with a high risk of small bowel cancer. The association of incomplete intestinal malrotation, duodenojejunal flexure tumor and celiac disease made the surgery challenging. CONCLUSION: Patients with celiac disease should be carefully monitored and endoscopic or radiologic investigations should be carried out in patients with any doubtful symptoms. PMID- 26670411 TI - A case of suboccipital lump with a rare and unexpected diagnosis of apocrine cystadenoma. AB - INTRODUCTION: Cystadenoma of apocrine origin is a tumour of the sweat gland that is benign in nature. Classification of this pathology is based upon histological characteristics plus histochemical analysis. Prevalence of cystadenoma has been suggested to be quite rare, in the region of 1 in 1000 of subcutaneous biopsies observed. PRESENTATION OF CASE: We present a case of a 40 year old man referred by his GP with a suboccipital lump, present for some years. On examination the lump was approximately 4-5cm in diameter and an unusual punctum was present. The patient proceeded to an excision of the lesion and the gross specimen showed characteristics of a multiloculated cyst, measuring some 5cm*3.5cm. Histopathology of the tumour revealed an apocrine cystadenoma; there were no features suggestive of malignancy. DISCUSSION: Previous classification of cystadenoma via histological and immunohistochemical method; has revealed only two distinct entities and the term hydrocystoma was often used in place of cystadenoma. More recent studies have suggested that a third type can be identified via immunohistochemical analysis. This third type; apocrine hydrocystoma, reveals that those previously defined as eccrine in origin may also be related to the apocrine ducts. CONCLUSION: Apocrine cystadenoma remains a benign pathology and treatment should be focussed on excision, without need for further intervention. Apocrine cystadenoma remains a relatively rare pathology, though one which should not recur if adequate treatment is given. PMID- 26670412 TI - Post coital penile ring entrapment: A report of a non-surgical extrication method. AB - This case report shows how a simple but painstaking method of milking and levering in a slippery field was used to remove a thick metallic ring entrapped at the root of the penis after sexual intercourse. A ring can be removed easily from an organ if the inter-phase is made slippery. However this must be weighed against the handling difficulties posed by a wet slippery surface. With perseverance and the use of unconventional instrument, the ring was successfully extricated as a day case and without a surgical incision. PMID- 26670413 TI - Biologically Active Acetylenic Amino Alcohol and N-Hydroxylated 1,2,3,4 Tetrahydro-beta-carboline Constituents of the New Zealand Ascidian Pseudodistoma opacum. AB - The first occurrence of an acetylenic 1-amino-2-alcohol, distaminolyne A (1), isolated from the New Zealand ascidian Pseudodistoma opacum, is reported. The isolation and structure elucidation of 1 and assignment of absolute configuration using the exciton coupled circular dichroism technique are described. In addition, a new N-9 hydroxy analogue (2) of the known P. opacum metabolite 7 bromohomotrypargine is also reported. Antimicrobial screening identified modest activity of 1 toward Escherichia coli, Staphylococcus aureus, and Mycobacterim tuberculosis, while 2 exhibited a moderate antimalarial activity (IC50 3.82 MUM) toward a chloroquine-resistant strain (FcB1) of Plasmodium falciparum. PMID- 26670414 TI - Optogenetics Comes of Age: Novel Inhibitory Light-Gated Anionic Channels Allow Efficient Silencing of Neural Function. AB - Optogenetics, the developing field of research that uses light-switchable biochemical tools in a sophisticated technological approach to monitor or control neural function, is rapidly evolving with the discovery and development of novel microbial rhodopsins. Light-absorbing membrane proteins, as tools for brain research, are promoting new applications within the discipline of optogenetics. Light-gated rhodopsin ion channels with better intrinsic light sensitivity and improved resolution are needed to overcome some of the current limitations of existing molecules. The recent discovery of light-gated inhibitory anion channels opens new opportunities for studying physiological neural processes and, at the same time, represent a powerful approach for elucidating the mechanisms of neurological and mental disorders that could benefit from this approach. PMID- 26670415 TI - A new phenolic enamide and a new meroterpenoid from marine alga-derived endophytic fungus Penicillium oxalicum EN-290. AB - Ten secondary metabolites (1-10) including a new phenolic enamide, methyl (Z)-3 (3,4-dihydroxyphenyl)-2-formamidoacrylate (1), and a new meroterpenoid, 15 hydroxydecaturin A (2), were characterized from the EtOAc extracts of the marine alga-derived endophytic fungus Penicillium oxalicum EN-290. The structures of these compounds were elucidated on the basis of 1D and 2D NMR experiments and the absolute configuration of compound 2 was confirmed by electronic circular dichroism quantum calculations. Compound 1 showed potent activity against Staphylococcus aureus with an MIC value of 2.0 MUg/ml, which is stronger than that of the positive control (chloromycetin, with an MIC 4.0 MUg/ml). This compound also showed activity against harmful algal bloom causative species Nitzschia closterium with inhibition zones of 20, 16, and 10 mm at 20, 10, and 5 mg/ml, respectively. Interestingly, so far, this type of anti-HAB metabolites has only been found in the algal-derived isolate of P. oxalicum. It could probably be a defense of this fungus against environmental stress and threat of survival. PMID- 26670416 TI - Tolerance as a function of disapproval and respect: The case of Muslims. AB - The article assesses a disapproval-respect model of tolerance according to which tolerance is made possible when disapproval of others' beliefs, preferences, or practices is balanced by respect for them as equal fellow citizens. Employing a sample of Muslims living in Germany, we predicted and found that such respect was more predictive of outgroup toleration when respondents disapproved rather than approved of the outgroups' beliefs, preferences, or practices. Moreover, respondents who displayed the critical combination of extreme disapproval and full respect indeed showed outgroup toleration. A parallel pattern of results was observed for willingness to engage in intergroup cooperation. Practical implications are discussed. PMID- 26670417 TI - Hierarchical honeycomb auxetic metamaterials. AB - Most conventional materials expand in transverse directions when they are compressed uniaxially resulting in the familiar positive Poisson's ratio. Here we develop a new class of two dimensional (2D) metamaterials with negative Poisson's ratio that contract in transverse directions under uniaxial compressive loads leading to auxeticity. This is achieved through mechanical instabilities (i.e., buckling) introduced by structural hierarchy and retained over a wide range of applied compression. This unusual behavior is demonstrated experimentally and analyzed computationally. The work provides new insights into the role of structural organization and hierarchy in designing 2D auxetic metamaterials, and new opportunities for developing energy absorbing materials, tunable membrane filters, and acoustic dampeners. PMID- 26670420 TI - Renal toxic ingredients and their toxicology from traditional Chinese medicine. AB - INTRODUCTION: There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED: This review summarizes the ingredients with renal toxicity from some TCMs through searching the relevant literature published over the past two decades. Renal toxicity components from TCMs include aristolochic acids (AAS), alkaloids, anthraquinones and others. TCM renal toxicity is most commonly caused by AAS and some alkaloids. AAS mainly come from Aristolochia contorta Bunge, Aristolochia manshuriensis Kom, Clematis Chinensis Osbeck, Aristolochia cathcartii Hook. Some renal toxic alkaloids are derived from Tripterygium regelii Sprague et Takeda, Stephania tetrandra S. Moore, Strychnos nux-vomica Linn. and Aconitum carmichaeli Debx. A few kinds of anthraquinones, flavonoids, and glycosides from TCMs also cause renal toxicity. All of these renal toxicity components and their associated renal toxicity, structures and toxic mechanism are introduced in detail in this review. EXPERT OPINION: Given the complexity of the toxic components, a lot of work needs to be done to analyze the specific modes of action of toxic components in vivo and in vitro, in particular, to elucidate the molecular mechanism of toxicity, in order to reduce the occurrence of renal toxicity of TCM. PMID- 26670421 TI - Novel Iron-based ternary amorphous oxide semiconductor with very high transparency, electronic conductivity, and mobility. AB - Here we report that ternary metal oxides of type (Me)2O3 with the primary metal (Me) constituent being Fe (66 atomic (at.) %) along with the two Lanthanide elements Tb (10 at.%) and Dy (24 at.%) can show excellent semiconducting transport properties. Thin films prepared by pulsed laser deposition at room temperature followed by ambient oxidation showed very high electronic conductivity (>5 * 10(4) S/m) and Hall mobility (>30 cm(2)/V-s). These films had an amorphous microstructure which was stable to at least 500 degrees C and large optical transparency with a direct band gap of 2.85 +/- 0.14 eV. This material shows emergent semiconducting behavior with significantly higher conductivity and mobility than the constituent insulating oxides. Since these results demonstrate a new way to modify the behaviors of transition metal oxides made from unfilled d and/or f-subshells, a new class of functional transparent conducting oxide materials could be envisioned. PMID- 26670418 TI - A systematic review of real-world diabetes prevention programs: learnings from the last 15 years. AB - BACKGROUND: The evidence base for the prevention of type 2 diabetes mellitus (T2DM) has progressed rapidly from efficacy trials to real-world translational studies and practical implementation trials over the last 15 years. However, evidence for the effective implementation and translation of diabetes programs and their population impact needs to be established in ways that are different from measuring program effectiveness. We report the findings of a systematic review that focuses on identifying the critical success factors for implementing diabetes prevention programs in real-world settings. METHODS: A systematic review of programs aimed at diabetes prevention was undertaken in order to evaluate their outcomes using the penetration, implementation, participation, and effectiveness (PIPE) impact metric. A search for relevant articles was carried out using PubMed (March 2015) and Web of Science, MEDLINE, CENTRAL, and EMBASE. A quality coding system was developed and included studies were rated independently by three researchers. RESULTS: Thirty eight studies were included in the review. Almost all (92 %) provided details on participation; however, only 18 % reported the coverage of their target population (penetration). Program intensity or implementation-as measured by frequency of contacts during first year and intervention duration-was identified in all of the reported studies, and 84 % of the studies also reported implementation fidelity; however, only 18 % of studies employed quality assurance measures to assess the extent to which the program was delivered as planned. Sixteen and 26 % of studies reported 'highly' or 'moderately' positive changes (effectiveness) respectively, based on weight loss. Six (16 %) studies reported 'high' diabetes risk reduction but 'low' to 'moderate' weight loss only. CONCLUSION: Our findings identify that program intensity plays a major role in weight loss outcomes. However, programs that have high uptake-both in terms of good coverage of invitees and their willingness to accept the invitation-can still have considerable impact in lowering diabetes risk in a population, even with a low intensity intervention that only leads to low or moderate weight loss. From a public health perspective, this is an important finding, especially for resource constrained settings. More use of the PIPE framework components will facilitate increased uptake of T2DM prevention programs around the world. PMID- 26670422 TI - Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials. AB - ESSENTIALS: Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population. We conducted separate meta-analyses of anticoagulant therapy in three different populations. Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population. Further randomized controlled trials should focus on specific populations with septic DIC. SUMMARY: BACKGROUND: Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis induced disseminated intravascular coagulation (DIC). OBJECTIVE: We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis. METHODS: We conducted separate meta analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis-induced coagulopathy, and (iii) population with sepsis-induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all-cause mortality as the primary outcome and bleeding complications as the secondary outcome. RESULTS: We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis-induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62-0.85) in the population with sepsis-induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations. CONCLUSION: Although associated with an increased risk of bleeding, anticoagulant therapy resulted in no survival benefits in the overall sepsis population and even the population with sepsis-induced coagulopathy; beneficial effects on mortality were observed only in the population with sepsis induced DIC. PMID- 26670423 TI - Characteristics, incidence and temporal trends of sepsis in elderly patients undergoing surgery. AB - BACKGROUND: Despite increasing rates of surgery in the elderly, there is limited population-based information on sepsis in this age group. This study aimed to characterize the epidemiology and national trends of sepsis among elderly patients undergoing surgery in Spain. METHODS: This population-based longitudinal study of patients aged 65 years or older, undergoing surgery between 2006 and 2011, used data from the national hospital discharge database. Patients were identified by ICD coding. Primary endpoints were incidence and case-fatality rates of sepsis. Predefined age groups were examined. In-hospital mortality related factors were assessed by means of exploratory logistic regression. Trends were assessed for annual percentage change in rates using Joinpoint regression analysis. RESULTS: A total of 44 342 episodes of sepsis were identified, representing 1.5 per cent of all 2 871 199 surgical hospital admissions of patients aged 65 years or older. The rates varied with age and sex. The in hospital case-fatality rate was 43.9 per cent (19 482 patients), and associated with age, co-morbidity and organ dysfunction. Standardized rates of sepsis increased over time, with an annual change of 4.7 (95 per cent c.i. 1.4 to 8.5) per cent, whereas the case-fatality rate declined, with an overall annual change of -3.6 (-4.3 to -2.8) per cent. The decrease in mortality was more limited in patients with organ dysfunction and in the oldest age group. CONCLUSION: Rates of sepsis are increasing among elderly patients undergoing surgery, whereas in hospital case fatality, although common, is showing a decreasing trend. PMID- 26670424 TI - Incorporation of 5-ethynyl-2'-deoxyuridine (EdU) as a novel strategy for identification of the skewed X inactivation pattern in balanced and unbalanced X rearrangements. AB - X-chromosome inactivation occurs randomly in normal female cells. However, the inactivation can be skewed in patients with alterations in X-chromosome. In balanced X-autosome translocations, normal X is preferentially inactivated, while in unbalanced X alterations, the aberrant X is usually inactivated. Here, we present a novel strategy to verify the skewed X inactivation pattern through the incorporation of 5-ethynyl-2'-deoxyuridine (EdU) into cells, in 11 patients: five carriers of balanced X-autosome translocations and six of unbalanced X-chromosome alterations. Since EdU is a labeled nucleoside analog of thymidine, its incorporation during DNA synthesis can reveal late replication regions and the inactive X-chromosome. All EdU findings were validated by the human androgen receptor gene (HUMARA) assay. The late replication regions were easily and quickly visualized in all cells, where inactive Xs are marked with strong green fluorescence. It was observed that the normal X-chromosome was preferentially inactivated in patients with balanced X-autosome translocations; while the aberrant X-chromosome was inactivated in most cells from patients with unbalanced alterations. By performing the fluorescence-based EdU assay, the differences between the active and inactive X-chromosomes are more easily recognizable than by classic cytogenetic methods. Furthermore, EdU incorporation allows the observation of the late replication regions in autosomal segments present in X derivatives from X-autosome translocations. Therefore, EdU assay permits an accurate and efficient cytogenetic evaluation of the X inactivation pattern with a low-cost, easy to perform and highly reproducible technique. PMID- 26670425 TI - Lymphadenopathies in patients with renal cell carcinoma: clinical and pathological predictors of pathologically confirmed lymph node invasion. AB - INTRODUCTION: In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI). METHODS: At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status. RESULTS: Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9-4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1 1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI. CONCLUSIONS: Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology. PMID- 26670426 TI - Risk factors and prognostic factors of acute kidney injury in children: A retrospective study between 2003 and 2013. AB - Recent report on epidemiology of acute kidney injury (AKI) is lacking for Chinese children. We aimed to investigate the risk factors for stage and prognostic factors for renal recovery in hospitalized children. Pediatric patients (<=18 years old) admitted during 2003 to 2013 were enrolled in this study. AKI was defined and staged using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression analysis was performed to determine the risk factors and prognostic factors. The morbidity of pediatric AKI was 0.31% (205/65 237). There were 45 (22.0%) cases in stage III, 30 (14.6%) cases in stage II and 130 (63.4%) cases in stage III. The majority of etiologies were intrinsic renal defects (85.4%). Age, weight, vomit, etiology, blood urea nitrogen (BUN) at admission and several blood gas measurements were associated with AKI stage III. Age (OR=0.894; 95% CI, 0.832-0.962; P=0.003), vomit (OR=2.375; 95% CI, 1.058 5.333; P=0.036) and BUN at admission (OR=1.135; 95% CI, 1.085-1.187; P<0.001) were identified as independent risk factors for AKI stage III. After treatment, 172 (83.9%) patients achieved complete or partial recovery. The mortality was 3.9%. Variables were found as prognostic factors for renal recovery, such as age, stage, hospital stay, BUN at discharge, white blood cells, red blood cells, platelets (PLTs), blood pH and urine blood. Among them, AKI stage (stage III vs. stage I; OR, 6.506; 95% CI, 1.640-25.816; P=0.008), BUN at discharge (OR, 0.918; 95% CI, 0.856-0.984; P=0.016) and PLTs (OR, 1.007; 95% CI, 1.001-1.013; P=0.027) were identified as independent prognostic factors. AKI is still common in Chinese hospitalized children. Identified risk factors and prognostic factors provide guiding information for clinical management of AKI. PMID- 26670427 TI - Is there comparable morbidity in pylorus-preserving and pylorus-resecting pancreaticoduodenectomy? A meta-analysis. AB - Pancreaticoduodenectomy (PD) is the most effective treatment for patients with pancreatic head or periampullary lesions. Two major strategies exist: pylorus preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). However, it is yet unclear regarding the morbidity after PPPD and PRPD. This study analyzed the morbidity after PPPD and PRPD to determine the optimal surgical treatment of masses in the pancreatic head or periampullary region. A systematic search of databases identifying randomized controlled trials (RCTs) from the Cochrane Library, PubMed, EMBASE and Web of Science was performed. Outcome was compared by postoperative morbidity including overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and delayed gastric emptying (DGE) rate between PPPD and PRPD. The DGE rate in the PRPD subgroups (conventional PD [CPD] and subtotal stomach-preserving PD [SSPPD], respectively) was also analyzed. The results showed that 9 RCTs including 722 participants were included for meta-analysis. Among these RCTs, 7 manuscripts described PRPD as CPD, and 2 manuscripts described PRPD as SSPPD. There were no significant differences in the overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, or biliary leakage between PPPD and PRPD. There was a lower rate of DGE with PRPD than that with PPPD (RR=2.15, P=0.03, 95% CI, 1.09-4.23). Further subgroup analysis indicated a comparable DGE rate for the CPD but a lower DGE rate for the SSPPD group than the PPPD group. However, the result did not indicate any difference between CPD and SSPPD regarding the DGE rate (P=0.92). It is suggested that PPPD is comparable to PRPD in overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding and biliary leakage. The current data are not sufficient to draw a conclusion regarding which surgical procedure is associated with a lower postoperative DGE rate. Our conclusions were limited by the available data. Further evaluations of RCTs are needed. PMID- 26670428 TI - Risk factors of hypertensive disorders among Chinese pregnant women. AB - The prevalence of hypertensive disorders in China was much higher than that in the United States. Considering the large population with wide geographic area of China, we aimed to add more information regarding the risk factors for hypertensive disorders of pregnancy. A case-control study was performed on 373 hypertensive cases and 507 normotensive controls. Participants were recruited from 2008 to 2014 in Yichang Maternal and Child Health Care Center in Hubei province and Anyang Maternal and Child Health Care Hospital in Henan province, China. Socio-demographic factors, family- related factors, pregnancy-associated factors, factors related to daily life behaviors and psychosocial factors were investigated with respect to hypertensive disorders in pregnancy through well designed questionnaire. Chi-square test, t-test, univariate logistic regression analysis, and multivariate logistic regression analysis were used to find the possible risk factors behind hypertensive disorders in pregnancy. The results showed that family history of cardiovascular diseases (OR=6.18, 95% CI, 2.37 to 16.14), history of pregnancy-induced hypertension (OR=16.64, 95% CI, 5.74 to 48.22), low maternal educational level (OR=2.81, 95% CI, 1.30 to 6.04), and poor relationship with their parents-in-law (OR=3.44, 95% CI, 1.55 to 7.59) had statistically significant associations with hypertensive disorders in pregnancy through multivariate logistic regression analysis. Increased maternal age, increased pre-pregnancy body mass index, living in rural area, low paternal education level, family history of hypertension, passive smoking one year before and/or in pregnancy, and poor sleeping quality were significantly associated with hypertensive disorders in pregnancy from univariate logistic regression analysis while the associations became uncertain when they were entered for multivariate logistic regression analysis. It was concluded that family history of cardiovascular diseases, history of pregnancy-induced hypertension, low maternal educational level, and poor relationship with their parents-in-law were independent risk factors for hypertensive disorders among Chinese pregnant women. PMID- 26670429 TI - Use of Chinese herbal medicine therapies in comprehensive hospitals in central China: A parallel survey in cancer patients and clinicians. AB - Chinese herbal medicine (CHM), as the largest application category of traditional Chinese medicine (TCM), is widely accepted among cancer patients in China. Herbal slice (HS) and Chinese patent drug (CPD) are commonly used CHM in China. This study aimed to investigate the utilization of CHM among clinicians and cancer patients in central China. Five hundred and twenty-five patients and 165 clinicians in 35 comprehensive hospitals in central China were asked to complete an anonymous questionnaire that was designed to evaluate the use of CHM. The results showed that 90.74% clinicians and 72.24% cancer patients used CHM during cancer treatment. The educational backgrounds of the clinicians and the age, education level, annual income, and cancer stage of the cancer patients were related to use of CHM. More than 90% clinicians and cancer patients had used CPD. Comparatively, the percentage of HS use was 10% lower than that of CPD use among clinicians and cancer patients. More clinicians preferred to use CHM after surgery than cancer patients did (20.41% vs. 5.37%). Enhancing physical fitness and improving performance status were regarded as the most potential effect of CHM on cancer treatment (85.71% among clinicians and 94.07% among cancer patients), in comparison with directly killing tumor cells (24.49% among clinicians and 31.36% among patients). As for refusal reasons, imprecise efficacy was the unanimous (100%) reason for clinicians' rejection of CHM, and 95.58% patients objected to using CHM also for this reason. Furthermore, the side effects of CHM were more concerned by clinicians than by patients (33.33% vs. 15.81%). In conclusion, our survey revealed that CHM was popularly accepted by clinicians and cancer patients in central China. The reasons of use and rejection of CHM were different between clinicians and cancer patients. PMID- 26670430 TI - Prevalence and related risk factors of anxiety and depression among Chinese college freshmen. AB - Anxiety, depression, and even suicidal ideation are becoming the most common mental health problems affecting Chinese college students. The present study investigated the prevalence of mental health problems and their predictors in a sample of 1048 Chinese college freshmen from Shanghai. We used following brief screening instruments to measure symptoms of anxiety and depression, as well as self-control and suicidal ideation: the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder scale (GAD-7), a mental health and mental health knowledge questionnaire (MK), a mental disease-related attitude questionnaire (MA), questionnaires about the knowledge of psychological services and utilities, the Mini International Neuropsychiatric Interview (MINI) Suicide module, the Self Rated Health Measurement Scale (SFHMS), the Self-Esteem Scale (SES), the Simplified Coping Style Questionnaire (SCQ), and the Perceived Stress Scale-10 (PSS-10). Over half of the students suffered from at least one mental health problem. Approximately 65.55% of freshmen had depression, and 46.85% had anxiety. Minority status, low family income, and religious belief were significantly associated with current mental health problems. These findings indicate that mental disorders are highly prevalent among the freshman student population. The prevalence of such mental disorders was greater than that of the general population, and the majority of students with mental health problems require treatment. PMID- 26670432 TI - MSCs relieve lung injury of COPD mice through promoting proliferation of endogenous lung stem cells. AB - Bone marrow mesenchymal stem cells (MSCs) transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD+MSCs group. The following indexes were detected: HE staining of lung tissue, the mean linear intercept (MLI) and alveolar destructive index (DI), the total cell number in bronchoalveolar lavage fluid (BALF), pulmonary function, alveolar wall apoptosis index (AI) and proliferation index (PI), the number of CD45(-)/CD31(-)/Sca-1(+) cells by flow cytometry (FCM), and the number of bronchoalveolar stem cells (BASCs) in bronchoalveolar duct junction (BADJ) by immunofluorescence. As compared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD+MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice. PMID- 26670431 TI - Dexamethasone decreases IL-29 expression in house dust mite-stimulated human bronchial epithelial cells. AB - The aim of this study was to explore the effect of IL-29 on the progression of airway allergic disease by detecting the level of IL-29 in airway allergic cell models stimulated by house dust mite (HDM) in the presence or absence of dexamethasone (DEX). The same batch of human bronchial epithelial cells in exponential growth phase was randomly divided into five groups: blank group (A), 300 ng/mL HDM group (B), 1000 ng/mL HDM group (C), 3000 ng/mL HDM group (D), and 300 ng/mL HDM+100 ng/mL DEX group (E). The IL-29 mRNA expression was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The IL-29 protein expression in cell suspension was detected by ELISA. The results showed that after stimulation with HDM for 24 h, the expression of IL-29 was increased significantly, and after co-stimulation with HDM and DEX for 24 h, the expression of IL-29 in group E was significantly lower than that in the groups stimulated by HDM alone but higher than that in the group A. The differences between the different groups were significant (F=132.957, P<0.01). Additionally, the higher the concentration of HDM was, the more significant the increase in the IL-29 expression was. In conclusion, IL-29 may play a role in the progression of airway allergic disease including asthma. PMID- 26670433 TI - Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer. AB - The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF 1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF 1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF 1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression. PMID- 26670434 TI - Altered expression profile of micrornas in gastric stromal tumor. AB - MicroRNAs (miRNAs) play important roles in carcinogenesis, but the global miRNA expression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology (GO) and pathway enrichment analysis. Total RNA was extracted and purified from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVanaTM miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays (version 4.0) containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrichment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The results showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up regulated (P<0.05). The validation results by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal tumor. miR 3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor. PMID- 26670435 TI - Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats. AB - The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication. PMID- 26670436 TI - Right ventricular outflow tract septal pacing versus apical pacing: A prospective, randomized, single-blind 5-years follow-up study of ventricular lead performance and safety. AB - Lead placement for ventricular pacing variably impacts the physiological benefit of the patient. This study evaluated the ventricular lead performance and safety of right ventricular outflow tract septal pacing in patients with bradyarrhythmia in South China over 60-month follow-up. Totally, 192 patients (108 males, and 84 females, 63+/-21 years old) with bradyarrhythmia were randomly divided into two groups. The right ventricular outflow tract septum (RVOTs) group had lead placement near the septum (n=97), while the right ventricular apex (RVA) group had a traditional apical placement (n=95). RV septal lead positioning was achieved with a specialized stylet and confirmed using fluoroscopic projection. All patients were followed up for 60 months. Follow-up assessment included stimulation threshold, R-wave sensing, lead impedance and lead complications. The time of electrode implantation in both the ROVTs and RVA groups were significantly different (4.29+/-0.61 vs. 2.16+/-0.22 min; P=0.009). No differences were identified in threshold, impedance or R-wave sensing between the two groups at 1st, 12th, 36th and 60th month during the follow-up period. No occurrence of electrode displacement, increased pacing threshold or inadequate sensing was found. The long-term active fixation ventricular electrode performance in RVOTs group was similar to that in RVA group. RVOTs pacing near the septum using active fixation electrodes may provide stability during long term follow-up period. PMID- 26670437 TI - Significance of normal range urinary albumin to creatinine ratio in Chinese subjects with metabolic syndrome. AB - This study was aimed to investigate clinical features of Chinese metabolic syndrome (MS) subjects with normal urinary albumin to creatinine ratio (UACR) and to estimate independent correlation factor for UACR. Data were drawn from a cross sectional survey in participants having MS. The patients with different grade of albuminuria were divided into 4 groups according to the value of UACR (<10, 10 20, 21-30, >30 mg/g). All underwent biochemical tests. Bioelectrical impedance body fat content, islet beta-cell function and insulin sensitivity were measured. Multivariable linear regression models were applied to further determine association between UACR and clinical factors with adjustment. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, fat mass, fat content and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly higher in the group with UACR at 10-20 mg/g than those in the group with UACA lower than 10 mg/g (P<0.05). Multivariable linear regression showed that TG, HbA1c, waist-hip ratio (WHR) and SBP were independently associated with UACR. The patients with normal UACR had abnormal levels of MS components. The factors independently associated with UACR were TG, HbA1c, WHR and SBP. PMID- 26670438 TI - Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats. AB - The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-alpha, NF-kappaB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up regulates TNF-alpha and NF-kappaB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-alpha, NF kappaB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-kappaB, and TNF-alpha, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all P<0.01). Splenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all P<0.01). The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring burn induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins. PMID- 26670439 TI - Expression and significance of HIF-1alpha and HIF-2alpha in pancreatic cancer. AB - The expression levels of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF 2alpha in pancreatic cancer (PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1alpha and HIF-2alpha mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1alpha and HIF-2alpha protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF 1alpha or HIF-2alpha and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1alpha and HIF-2alpha mRNA was up-regulated in most cancer tissues (P<0.05). HIF-1alpha staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues (P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1alpha expression in cancer tissues was related to greater invasion (P<0.05), higher tumor pathologic stage (P<0.05), higher American Joint Committee on Cancer (AJCC) stage (P<0.05) and shorter overall survival time (P<0.05). Conversely, HIF-2alpha staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2alpha expression in cancer tissues was related to less invasion (P<0.05), lower tumor pathologic stage (P<0.05), lower AJCC stage (P<0.05) and longer overall survival time (P<0.05). Moreover, the HIF-1alpha(high)/HIF 2alpha(low) group showed a shorter survival time than the HIF-1alpha(low)/HIF 2alpha(high) group. In conclusion, although HIF-1alpha and HIF-2alpha mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1alpha and HIF-2alpha expression might be useful to predict the prognosis of patients with PC. PMID- 26670440 TI - Protective effect of simvastatin on impaired intestine tight junction protein ZO 1 in a mouse model of Parkinson's disease. AB - Recently, several studies showed that gastrointestinal tract may be associated with pathophysiology of Parkinson's disease (PD). Intestine tight junction protein zonula occluden-1 (ZO-1) is an important component of intestinal barrier which can be degraded by matrix metallopeptidase 9 (MMP-9). In our previous study, a significant decline in ZO-1 was observed along with enhanced MMP-9 activity in the duodenum and distal colon of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-intoxicated mice. In this study, the protective effect of simvastatin on ZO-1 was investigated using an MPTP mouse model of PD. Seven days after the end of MPTP application, the expression level of ZO-1 was evaluated by immunohistochemistry. The protein expression levels of ZO-1 and MMP9 were detected by Western blotting. Meanwhile, MMP-9 activity was analyzed by gelatin zymography. MPTP treatment led to a decrease in the expression of ZO-1, which was accompanied by elevated MMP-9 activity. Treatment with simvastatin could partly reverse the MPTP-induced changes in ZO-1 expression and reduce MMP-9 protein and activity. Taken together, these findings suggest that simvastatin administration may partially reverse the impairment of ZO-1 induced by MPTP via inhibiting the activity of MMP9, fortify the impaired intestinal barrier and limit gut-derived toxins that pass across the intestinal barrier. PMID- 26670441 TI - Comparative analysis of general characteristics of ischemic stroke of BAD and non BAD CISS subtypes. AB - Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed. PMID- 26670442 TI - STAT3 correlates with stem cell-related transcription factors in cervical cancer. AB - Cancer stem cells (CSCs) are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 (STAT3) is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid (GV316-STAT3) and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 (cancer stem cell markers) and STAT3 was detected by quantitative real time PCR and immunoblotting for Siha cells and by immunohistochemistry (IHC) for cervical tissues, respectively. The results showed that Nanog+, Oct4+, and Sox2+ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere formation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells (P<0.05). Meanwhile, the expression levels of Oct4, Nanog and Sox2 mRNA and protein were significantly higher in Siha STAT3 overexprssing cells than in siRNA-STAT3 cells (P<0.05). In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group (P<0.05). There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression (all P<0.001). These results suggested that Oct4+, Sox2+, and Nanog+ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3. PMID- 26670443 TI - Clinicopathological significance of increased ZIC1 expression in human endometrial cancer. AB - Zinc finger of the cerebellum (ZIC1), one of ZIC family genes, has been shown to play important roles in many cancers such as gastric cancer and breast cancer. However, there is little known about the expression and significance of ZIC1 in endometrial cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of ZIC1 in endometrial cancer. The mRNA and protein expression of ZIC1 in endometrial cancer tissues was detected using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Immunostaining of ZIC1 in 99 endometrial cancer samples was examined and its associations with clinicopathological parameters were analyzed. Hec-1-B cells were transfected with ZIC1-shRNA or sc-shRNA, and cell proliferation was assayed. Hec-1-B cells stably transfected with ZIC1-shRNA or sc shRNA were subcutaneously inoculated into nude mice, and the tumor weight was measured. A significantly increased expression of ZIC1 mRNA and protein was observed in endometrial cancer tissues compared to that in normal endometrial tissues (P<0.05). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of ZIC1 was observed in almost all endometrial cancer samples (90/99) while light and moderate immunostaining of ZIC1 was only detected in 17 of 30 (56.7%) normal tissues. Moreover, up-regulation of ZIC1 was significantly correlated with age, disease stage, TNM stage and FIGO stage (P<0.05). The down regulated expression of ZIC1 contributed to the inhibition of cell proliferation, and inhibited the growth of tumor. It was concluded that ZIC1 is over-expressed in endometrial cancer tissue but not in normal tissue, and positively correlated to the malignant biological behavior of endometrial carcinogenesis. PMID- 26670444 TI - Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury. AB - Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 MUg/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1. PMID- 26670445 TI - Upregulation of toll-like receptor 4 on T cells in PBMCs is associated with disease aggravation of HBV-related acute-on-chronic liver failure. AB - Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure (ACLF). Toll-like receptors (TLRs) have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was to characterize the TLR4 expression in peripheral blood mononuclear cells (PBMCs) of ACLF patients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected (CHB) patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 expression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was analyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expression of TLR4 on CD4(+) and CD8(+) T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4(+) and CD8(+) T cells were positively correlated with serum total bilirubin (TBIL), direct bilirubin (DBIL), international normalized ratio (INR) levels and white blood cells (WBCs), and negatively correlated with serum albumin (ALB) levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF alpha production by CD4(+) T cells, which was also positively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF. PMID- 26670446 TI - Antiviral effect of emodin from Rheum palmatum against coxsakievirus B5 and human respiratory syncytial virus in vitro. AB - Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-gamma, TNF-alpha) mRNA expressions after emodin treatment (7.5, 15, 30 MUmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC50) ranging from 13.06 to 14.27 MUmol/L and selectivity index (SI) being 5.38-6.41 MUmol/L. However, emodin couldn't directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-alpha but enhance TNF-gamma expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy. PMID- 26670447 TI - Comparative study of DSC-PWI and 3D-ASL in ischemic stroke patients. AB - The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson's correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and-0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL <=0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL <=0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT. PMID- 26670448 TI - Prenatal diagnosis of sirenomelia by two-dimensional and three-dimensional skeletal imaging ultrasound. AB - This study sought to evaluate the contribution of two-dimensional ultrasound (2D US) and three-dimensional skeletal imaging ultrasound (3D-SUIS) in the prenatal diagnosis of sirenomelia. Between September 2010 and April 2014, a prospective study was conducted in a single referral center using 3D-SUIS performed after 2D US in 10 cases of sirenomelia. Diagnostic accuracy and detailed findings were compared with postnatal three-dimensional helical computed tomography (3D-HCT), radiological findings and autopsy. Pregnancy was terminated in all 10 sirenomelia cases, including 9 singletons and 1 conjoined twin pregnancy, for a total of 5 males and 5 females. These cases of sirenomelia were determined by autopsy and/or chromosomal examination. Initial 2D-US showed that there were 10 cases of oligohydramnios, bilateral renal agenesis, bladder agenesis, single umbilical artery, fusion of the lower limbs and spinal abnormalities; 8 cases of dipus or monopus; 2 cases of apus; and 8 cases of cardiac abnormalities. Subsequent 3D SUIS showed that there were 9 cases of scoliosis, 10 cases of sacrococcygeal vertebra dysplasia, 3 cases of hemivertebra, 1 case of vertebral fusion, 3 cases of spina bifida, and 5 cases of rib abnormalities. 3D-SUIS identified significantly more skeletal abnormalities than did 2D-US, and its accuracy was 79.5% (70/88) compared with 3D-HCT and radiography. 3D-SUIS seems to be a useful complementary method to 2D-US and may improve the accuracy of identifying prenatal skeletal abnormalities related to sirenomelia. PMID- 26670449 TI - Culture media influenced laboratory outcomes but not neonatal birth weight in assisted reproductive technology. AB - Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn's Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and chi (2) tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART. PMID- 26670450 TI - Comparison of three different techniques of human sperm DNA isolation for methylation assay. AB - Human sperm DNA is an important genetic and epigenetic material, whose chromatin structure differs from that of somatic cells. As such, conventional methods for DNA extraction of somatic cells may not be suitable for obtaining sperm DNA. In this study, we evaluated and compared three sperm DNA extraction techniques, namely, modified guanidinium thiocyanate method (method A), traditional phenol chloroform method (method B), and TianGen kit method (method C). Spectrophotometry and agarose gel electrophoresis analyses showed that method A produced DNA with higher quantity and purity than those of methods B and C (P<0.01). PCR results revealed that method A was more reliable in amplifying DEAD box polypeptide 4 (DDX4) and copy number variations (CNVs) than methods B and C, which generated false-positive errors. The results of sperm DNA methylation assay further indicated that methods A and B were effective, and the former yielded higher quantitative accuracy. In conclusion, the modified guanidinium thiocyanate method provided high quality and reliable results and could be an optimal technique for extracting sperm DNA for methylation assay. PMID- 26670452 TI - Association study between melanocortin-1 receptor gene polymorphisms and occurrence of vitiligo in a Taiwanese population: possible explanation for lack of increased UV-related damage in vitiligo skin. PMID- 26670451 TI - Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling. AB - Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID- 26670453 TI - Comparison of comorbidities of the Egyptian rheumatoid arthritis patients to the global cohort of the COMORA study: a post-hoc analysis. AB - The aims of this study are to present the results of Egyptian RA patients included in COMORA cohort and compare it to general COMORA cohort, concerning prevalence of comorbidities, and level of application of recommendations related to detection/prevention of comorbidities. Three-hundred eight Egyptian RA patients included in the cross-sectional, observational, multi-center, international study "COMORA", were compared to the total number of 3612 RA patients. The CRF of COMORA was used in all patients. CRF collects demographic and disease characteristics, comorbidities, risk factors, and compliance with recommendations regarding management of comorbidities. Data were analyzed according to COMORA protocol. Egyptian RA patients were significantly younger, had more active disease, and were more functionally disabled. They showed more frequent use of NSAIDs, methotrexate and steroids and significantly lower use of bDMARDs when compared to non-Egyptians. Egyptian patients had the highest ever HCV prevalence, while depression, hypertension, smoking and dyslipidemia were less prevalent in Egyptians. Prevalence of malignancy risk factors was highly deficient among Egyptians; primarily due to lack of screening. Further, following recommendations for monitoring comorbidities is significantly deficient among Egyptian patients. Egyptian patients had more active disease and more functional impairment than the rest of the COMORA cohort; with lower use of bDMARDs, that is possibly related to the economic situation. Also, there is a clear gap in screening and monitoring comorbidities. Awareness among Egyptian healthcare providers (and possibly similar third-world countries) to detect and manage RA related comorbidities is required. PMID- 26670454 TI - Performance characteristics of the simplified version of ankylosing spondylitis disease activity score (SASDAS). AB - Various types of disease activity measures are available for axial spondyloarthritis (axSpA), and there is no gold standard for all individual patients. The ankylosing spondylitis disease activity score (ASDAS) is highly discriminatory, sensitive to change, and associated with structural progression. A simplified version of the ASDAS (SASDAS) was proposed and found to be a simple and practical tool to assess disease activity. Our aim was to test the performance characteristics of the SASDAS and compare it with validated tools. In total, 97 consecutive ankylosing spondylitis (AS) patients were included in the study. Disease activity was assessed by the ASDAS-erythrocyte sedimentation rate (ESR), ASDAS-C-reactive protein (CRP), bath ankylosing spondylitis disease activity index (BASDAI), and SASDAS. The relationship among these activity indices and the level of agreement of various activity categories were tested. There was a strong correlation between the SASDAS and other activity indices, including the BASDAI (r = 0.916, p < 0.001), ASDAS-CRP (r = 0.847, p < 0.001), and ASDAS-ESR (r = 0.942, p < 0.001). Although the agreement between the ASDAS ESR and SASDAS was good (weighted kappa of 0.744 and total agreement of 77 %), there was moderate agreement between the ASDAS-CRP and SASDAS (weighted kappa of 0.579 and total agreement of 66 %). The disagreement was particularly striking in "moderate" and "high disease activity" states. Approximately 40 % of patients classified as moderate activity according to the ASDAS-ESR and 45 % according to the ASDAS-CRP were differentially categorized by the SASDAS. The results of the present analysis suggest that the simplified version of the ASDAS-ESR should be further validated in various settings and populations due to a questionable level of agreement between the ASDAS-CRP and SASDAS. PMID- 26670455 TI - Validity of Submaximal Step Tests to Estimate Maximal Oxygen Uptake in Healthy Adults. AB - BACKGROUND: Aerobic capacity (VO2max) is a strong predictor of health and fitness and is considered a key physiological measure in the healthy adult population. Submaximal step tests provide a safe, simple and ecologically valid means of assessing VO2max in both the general population and a rehabilitation setting. However, no studies have attempted to synthesize the existing knowledge regarding the validity of the multiple step-test protocols available to estimate VO2max in the healthy adult population. OBJECTIVES: The objective of this study was to systematically review literature on the validity and reliability of submaximal step-test protocols to estimate VO2max in healthy adults (age 18-65 years). DATA SOURCES AND STUDY SELECTION: A systematic literature search of the MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library databases was performed. The search returned 690 studies that underwent the initial screening process. To be included, the study had to (1) have participants deemed to be healthy and aged between 18 and 65 years; (2) assess VO2max by means of a submaximal step test against a graded exercise test (GXT) to volitional exhaustion; and (3) be available in English. Reference lists from included articles were screened for additional articles. DATA ANALYSIS AND STUDY APPRAISAL METHODS: The primary outcome measures used were the validity statistics between the actual measured VO2max and predicted VO2max values, and the reported direction of the statistically significant difference between the measured VO2max and the predicted VO2max. The Quality Assessment Tool for Quantitative Studies was used to assess the risk of bias in each included study, and was adapted to the type of quantitative study design used. RESULTS: The combined database search produced 690 studies, from which 644 were excluded during the screening process. Following full-text assessment, a further 39 studies were excluded based on the eligibility criteria detailed previously. Four additional studies were located via the reference lists of the included studies, leaving 11 studies that fulfilled the inclusion criteria and which compared eight different step-test protocols against a direct measure of VO2max incurred during a maximal GXT. Validity measures varied, with a broad range of correlation coefficients reported across the 11 studies (r = 0.469-0.95). Of the 11 studies, two reported reliability measures, demonstrating good test-retest reliability [mean -0.8 +/- 3.7 mL kg(-1) min(-1) (+/-7.7 % of the mean measured VO2max)]. CONCLUSIONS: Considering the relationship between VO2max and various markers of health, the use of step tests as a measure of health in both the general adult population and rehabilitation settings is advocated. Step tests provide a simple, effective and ecologically valid method of submaximally assessing VO2max that can be implemented in a variety of situations within the general adult population. Future research is needed to assess the reliability of the majority of the step-test procedures reviewed. Based on the validity measures, submaximal step-test protocols are an acceptable means of estimating VO2max in the generally healthy adult population. For tracking changes in cardiorespiratory fitness, the Chester Step test appears to be an appropriate tool due to its high test-retest reliability. PMID- 26670456 TI - Agility in Team Sports: Testing, Training and Factors Affecting Performance. AB - BACKGROUND: Agility is an important characteristic of team sports athletes. There is a growing interest in the factors that influence agility performance as well as appropriate testing protocols and training strategies to assess and improve this quality. OBJECTIVE: The objective of this systematic review was to (1) evaluate the reliability and validity of agility tests in team sports, (2) detail factors that may influence agility performance, and (3) identify the effects of different interventions on agility performance. METHODS: The review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a search of PubMed, Google Scholar, Science Direct, and SPORTDiscus databases. We assessed the methodological quality of intervention studies using a customized checklist of assessment criteria. RESULTS: Intraclass correlation coefficient values were 0.80 0.91, 0.10-0.81, and 0.81-0.99 for test time using light, video, and human stimuli. A low-level reliability was reported for youth athletes using the video stimulus (0.10-0.30). Higher-level participants were shown to be, on average, 7.5% faster than their lower level counterparts. Reaction time and accuracy, foot placement, and in-line lunge movement have been shown to be related to agility performance. The contribution of strength remains unclear. Efficacy of interventions on agility performance ranged from 1% (vibration training) to 7.5% (small-sided games training). CONCLUSIONS: Agility tests generally offer good reliability, although this may be compromised in younger participants responding to various scenarios. A human and/or video stimulus seems the most appropriate method to discriminate between standard of playing ability. Decision-making and perceptual factors are often propositioned as discriminant factors; however, the underlying mechanisms are relatively unknown. Research has focused predominantly on the physical element of agility. Small-sided games and video training may offer effective methods of improving agility, although practical issues may hinder the latter. PMID- 26670457 TI - Heat shock protein 70 gene polymorphisms' influence on the electrophysiology of long QT syndrome. AB - PURPOSE: Long QT syndrome (LQTS) is a rare cardiac disorder caused due to mutations in genes encoding ion channels responsible for generation of electrical impulses. The heat shock protein (HSP)-70 gene, expressed under conditions of stress, plays a cardioprotective role when overexpressed and helps in the proper folding of the nascent proteins synthesized by the cellular machinery. We aimed to identify the role played by HSP-70 gene polymorphisms in the pathogenesis of LQTS. METHODS: Study included 49 LQTS patients, 71 family members, and 219 healthy individuals recruited from an ethnically matched population. Genotyping of the single-nucleotide polymorphisms (SNPs) rs1043618 (HSP-70-1, +190G/C), rs1061581 (HSP-70-2, +1267A/G), and rs2227956 (HSP-70-hom, +2437T/C) was performed by PCR-RFLP analysis, and the results were analyzed statistically at 95 % confidence interval and p <= 0. 05. RESULTS: The "C" allele of HSP-70-1 (+190G/C) and "G" allele of HSP-70-2 (+1267A/G) showed strong association with LQTS phenotype. The haplotype group C-G-T consisting of two risk alleles was significantly associated with the disease condition. Multifactor dimensionality reduction analysis further substantiated that the three-allele model influences the outcome of the phenotype highlighting the effect of modifiers in the etiology of LQTS. CONCLUSIONS: As HSP-70 influences the channel assembly and maturation/trafficking of the ion channel proteins, the alleles C of the HSP-70-1 and G of the HSP-70-2 loci and the haplotype group C-G-T could be considered a diagnostic biomarker in the identification of the LQTS phenotype with a potential to affect the progression and modification of the disease phenotype. PMID- 26670458 TI - Implementation of stress-only imaging: What will it take? PMID- 26670460 TI - Oral health screening should be routine in professional football: a call to action for sports and exercise medicine (SEM) clinicians. PMID- 26670459 TI - A prospective longitudinal model predicting early adult alcohol problems: evidence for a robust externalizing pathway. AB - BACKGROUND: Risk factors for alcohol problems (AP) include biological and environmental factors that are relevant across development. The pathways through which these factors are related, and how they lead to AP, are optimally considered in the context of a comprehensive developmental model. METHOD: Using data from a prospectively assessed, population-based UK cohort, we constructed a structural equation model that integrated risk factors reflecting individual, family and peer/community-level constructs across childhood, adolescence and young adulthood. These variables were used to predict AP at the age of 20 years. RESULTS: The final model explained over 30% of the variance in liability to age 20 years AP. Most prominent in the model was an externalizing pathway to AP, with conduct problems, sensation seeking, AP at age 17.5 years and illicit substance use acting as robust predictors. In conjunction with these individual-level risk factors, familial AP, peer relationships and low parental monitoring also predicted AP. Internalizing problems were less consistently associated with AP. Some risk factors previously identified were not associated with AP in the context of this comprehensive model. CONCLUSIONS: The etiology of young adult AP is complex, influenced by risk factors that manifest across development. The most prominent pathway to AP is via externalizing and related behaviors. These findings underscore the importance of jointly assessing both biologically influenced and environmental risk factors for AP in a developmental context. PMID- 26670461 TI - Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma. AB - Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC. PMID- 26670462 TI - Effectiveness of maternal influenza immunization in young infants in Japan. AB - BACKGROUND: Infants with influenza, particularly those younger than 1 year of age, are at high risk of developing a severe case or of dying. Recently, owing to the spread of pandemic influenza A (H1N1) 2009, the Advisory Committee on Immunization Practices recommended maternal immunization to reduce the risk of influenza infection in pregnant women and infants. Such reporting is rare in Japan. The aim of this study was therefore to investigate the effect on the newborn of influenza vaccination of pregnant women in Japan. METHODS: The study included 200 infants who were born to healthy mothers at Kobayashi Ladies Clinic during influenza season from November 2010 to April 2011. The incidence of fever and laboratory-confirmed influenza was assessed in the infants for the 6 months after their birth. RESULTS: Of the 200 infants, four were excluded from this study due to loss to follow up. The 106 infants in the group whose mothers received the influenza vaccine (vaccinated group) before parturition were compared with the 90 infants in the group whose mothers did not receive the influenza vaccine (non-vaccinated group). Fever was noted in 36 infants (34.0%) in the vaccinated group and in 47 infants (52.2%) in the non-vaccinated group (P < 0.007), and the incidence of influenza was 0 (0%) and 5 (5.6%), respectively (P = 0.019). The incidence of fever and influenza among infants was significantly lower in the vaccinated group compared with the non-vaccinated group. CONCLUSIONS: Maternal influenza immunization should be actively recommended in Japan to protect newborns from influenza viruses. PMID- 26670463 TI - Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study. AB - The efficacy of radiotherapy on tumors is hampered by its devastating adverse effects on healthy tissue, particularly that of the gastrointestinal tract. These effects cause acute symptoms that are so disruptive to patients that they can lead to interruption of the radiotherapy program. These adverse effects could limit the intensity of radiation received by the patient, resulting in a sublethal dose to the tumor, thus increasing the risk of tumor resistance. The lack of an effective treatment to protect the bowel during radiation therapy to allow higher radiation doses that are lethal to the tumor has become a barrier to implementing effective therapy. In this study, we present a comparative analysis of both intestinal and tumor tissue in regard to the efficacy and the preventive impact of a short-term growth hormone (GH) treatment in tumor-bearing rats as a protective agent during radiotherapy. Our data show that the exogenous administration of GH improved intestinal recovery after radiation treatment while preserving the therapeutic effect against the tumor. GH significantly increased proliferation in the irradiated intestine but not in the irradiated tumors, as assessed by Positron Emission Tomography and the proliferative markers Ki67, cyclin D3, and Proliferating Cell Nuclear Antigen. This proliferative effect was consistent with a significant increase in irradiated intestinal villi and crypt length. Furthermore, GH significantly decreased caspase-3 activity in the intestine, whereas GH did not produce this effect in the irradiated tumors. In conclusion, short-term GH treatment protects the bowel, inducing proliferation while reducing apoptosis in healthy intestinal tissue and preserving radiotherapy efficacy on tumors. PMID- 26670465 TI - Pain and the global burden of disease. PMID- 26670464 TI - Small Tails Tell Tall Tales--Intra-Individual Variation in the Stable Isotope Values of Fish Fin. AB - BACKGROUND: Fish fin is a widely used, non-lethal sample material in studies using stable isotopes to assess the ecology of fishes. However, fish fin is composed of two distinct tissues (ray and membrane) which may have different stable isotope values and are not homogeneously distributed within a fin. As such, estimates of the stable isotope values of a fish may vary according to the section of fin sampled. METHODS: To assess the magnitude of this variation, we analysed carbon (delta13C), nitrogen (delta15N), hydrogen (delta2H) and oxygen (delta18O) stable isotopes of caudal fin from juvenile, riverine stages of Atlantic salmon (Salmo salar) and brown trout (Salmo trutta). Individual fins were sub-sectioned into tip, mid and base, of which a further subset were divided into ray and membrane. FINDINGS: Isotope variation between fin sections, evident in all four elements, was primarily related to differences between ray and membrane. Base sections were13C depleted relative to tip (~10/00) with equivalent variation evident between ray and membrane. A similar trend was evident in delta2H, though the degree of variation was far greater (~100/00). Base and ray sections were 18O enriched (~20/00) relative to tip and membrane, respectively. Ray and membrane sections displayed longitudinal variation in 15N mirroring that of composite fin (~10/00), indicating that variation in15N values was likely related to ontogenetic variation. CONCLUSIONS: To account for the effects of intra-fin variability in stable isotope analyses we suggest that researchers sampling fish fin, in increasing priority, 1) also analyse muscle (or liver) tissue from a subsample of fish to calibrate their data, or 2) standardize sampling by selecting tissue only from the extreme tip of a fin, or 3) homogenize fins prior to analysis. PMID- 26670467 TI - Self-assembly preparation of SiO2@Ni-Al layered double hydroxide composites and their enhanced electrorheological characteristics. AB - The core-shell structured SiO2@Ni-Al layered double hydroxide (LDH) composites were prepared via self-assembly of Ni-Al LDH on the surface of SiO2 spheres. Only coating a layer of ultrathin Ni-Al LDH sheet, the resulting SiO2@Ni-Al LDH composites exhibit significantly enhanced electrorheological (ER) characteristics compared to conventional bare SiO2 spheres. The monodispersed SiO2 spheres with average diameters of 260 nm were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS), while the shell part, Ni-Al LDH sheet was prepared by the hydrothermal procedure. The morphology of the samples was investigated via scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The structure of the samples was characterized by X-ray diffraction (XRD). The species and distribution of elements in samples were confirmed by X-ray photoelectron spectroscopy (XPS), Energy dispersive analysis of X-ray (EDX) and elemental mapping in STEM. Subsequently, the ER characteristics of the composites dispersed in insulating oil were characterized by a rotational rheometer. The electric field-stimulated rheological performances (yield stress, viscosity, modulus, etc.) were observed under an external electric field, which is different from the Newtonian state in the free electric field. PMID- 26670466 TI - ReACT Phase II trial: a critical evaluation of the use of rindopepimut plus bevacizumab to treat EGFRvIII-positive recurrent glioblastoma. AB - Glioblastoma is the most deadly primary brain tumor in adults and has long represented a therapeutic challenge. Disease recurrence is inevitable, and the management of recurrent disease is complicated by spontaneous or induced tumor heterogeneity which confers resistance to therapy and increased oncogenicity. EGFR and the tumor-specific mutation EGFRvIII is commonly altered in glioblastoma making it an appealing therapeutic target. Immunotherapy is an emerging and promising therapeutic approach to glioma and the EGFRvIII vaccine, rindopepimut, is the first immunotherapeutic drug to enter Phase III clinical trials for glioblastoma. Rindopepimut activates a specific immune response against tumor cells harboring the EGFRvIII protein. This review evaluates the recently completed ReACT Phase II trial using rindopepimut plus bevacizumab in the setting of EGFRvIII-positive recurrent glioblastoma (Clinical Trials identifier: NCT01498328). PMID- 26670469 TI - Review of Ultrasound-Guided Radial Artery Catheter Placement. AB - Radial artery catheters are commonly placed for continuous blood pressure monitoring, frequent arterial blood gas analysis, or frequent blood sampling for diagnostic testing. Radial artery cannulation can be challenging and ultrasound guidance has emerged as a valuable adjunct for the placement of radial artery catheters. The advantages of ultrasound guidance include: real-time visualization of landmarks, improved pre-procedure planning, reduction in complications, less time spent at the bedside, and improved first-attempt success rates. Disadvantages of ultrasound guidance include: equipment cost, equipment availability, limited availability of experts to train providers, and the cost of training providers. Ultrasound machines are readily available and widely utilized in many emergency departments, operating rooms, and ICUs. We will summarize the use of ultrasound guidance for the placement of radial artery catheters and describe the techniques used during ultrasound-guided arterial catheter placement. Training on the use of ultrasound should be encouraged for all practitioners who place radial artery catheters. PMID- 26670468 TI - Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals. AB - OBJECTIVES: We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA. METHODS: Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry. RESULTS: The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis. CONCLUSIONS: In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals. PMID- 26670470 TI - Smoking-Related Behaviors and Effectiveness of Smoking Cessation Therapy Among Prisoners and Prison Staff. AB - BACKGROUND: Smoking is a serious problem in prisons. This work aimed to assess smoking-related behaviors and the effectiveness of tobacco cessation therapy in prison. METHODS: This study includes four visits to a prison in Bolvadin-Afyon, Turkey. Pharmacologic options for tobacco cessation were offered to the participants who wanted to quit smoking. RESULTS: One hundred seventy-nine subjects (109 prisoners and 70 prison staff) with 68.7% current smokers were included. There was an increase of cigarette smoking in 41.8% (the most common reason was stress) and decrease in 18.7% (the most common reason was health problems) of the participants after incarceration. Fifty-nine participants accepted the offered tobacco cessation treatment. Only 2 participants started their planned medications, but they could not quit smoking. The most common reason for failed attempts to quit was the high prices of cessation therapies. CONCLUSION: Factors like stress and being in prison may provoke smoking. A smoking ban does not seem to be a total solution for preventing tobacco use in prisons. Tobacco cessation programs may be a better option. Cost-free cessation medications may increase quitting rates among prisoners and prison staff. PMID- 26670471 TI - Description of Respiratory Microbiology of Children With Long-Term Tracheostomies. AB - BACKGROUND: There is little evidence in the medical literature to guide empiric treatment of pediatric patients with long-term tracheostomies who present with signs and symptoms of a bacterial respiratory infection. The overall goal of this study was to describe the respiratory microbiology in this study population at our institution. METHODS: This study was a retrospective chart review of all subjects with tracheostomies currently receiving care at the Arkansas Center for Respiratory Technology Dependent Children. Descriptive statistics were used to describe the respiratory microbiology of the full study group. Several subgroup analyses were conducted, including description of microbiology according to time with tracheostomy, mean time to isolation of specific organisms after the tracheostomy tube was placed, association between Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus isolation and prescribed antibiotic courses, and description of microbiology according to level of chronic respiratory support. Available respiratory culture results up to July 2011 were collected for all eligible subjects. Descriptive statistics were used to describe subject characteristics, and chi-square analysis was used to analyze associations between categorical data. P < .05 was considered statistically significant. RESULTS: A total of 93 subjects met inclusion criteria for the study. The median (interquartile range) age at time of tracheotomy was 0.84 (0.36-3.25) y, and the median (interquartile range) time with tracheostomy was 4.29 (2.77-9.49) y. The most common organism isolated was P. aeruginosa (90.3%), with Gram-negative organisms predominating. However, 55.9% of the study population had a respiratory culture positive for methicillin-resistant S. aureus. The first organism isolated after tracheostomy placement was Methiciliin-sensitive S. aureus was isolated the soonest after tracheostomy placement. Specific organisms were not related to level of chronic respiratory support or likelihood of receiving antibiotics. CONCLUSIONS: This study provides an updated overview of the variety of potential pathogens isolated from respiratory cultures of pediatric subjects with long-term tracheostomies. PMID- 26670472 TI - Ventilator Settings to Avoid Nuisance Alarms During Mouthpiece Ventilation. AB - BACKGROUND: A recent study found that activation of disconnection and low pressure alarms is common during mouthpiece ventilation and may represent a major limitation to its use. The aim of this bench study was: (1) to investigate the technical aspects that can influence the setting of the ventilator during mouthpiece ventilation and (2) to provide a practical setting strategy to avoid the alarm activation. METHODS: Eight life-support ventilators able to deliver volume controlled ventilation were tested in a bench study using a single-limb non-vented circuit configuration connected to a standard mouthpiece. Disconnection and apnea alarm were turned off or set at the least sensitive setting. The backup frequency was set at the lowest available level. Different tidal volumes (VT) (from 500 to 1,200 mL) were tested with the rectangular and descending flow shape. For each VT, we reported the maximum set inspiratory time (TI) that allowed preventing activation of the low-pressure alarm. The presence of auto-triggering was also surveyed. RESULTS: We found that a correct combination of VT and TI avoided the activation of disconnection and low-pressure alarms in all but 3 ventilators. One ventilator did not allow mouthpiece ventilation independently from the settings used. The inability to turn off the apnea alarm in two other ventilators led to the alarm going off in any tested conditions after 120 s without triggered breaths. Auto-triggering was seldom found and easily worked out, except for in one ventilator. CONCLUSIONS: An appropriate alarm setting and combination of VT and TI would allow the majority of the tested ventilators to be used for mouthpiece ventilation without alarm activation. PMID- 26670473 TI - Is Thrombocytopenia an Early Prognostic Marker in Septic Shock? AB - OBJECTIVES: To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. DESIGN: Prospective, multicenter, observational cohort study. SETTING: Fourteen ICUs from 10 French university teaching and nonacademic hospitals. PATIENTS: Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p <= 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p < 0.0001). CONCLUSIONS: This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock. PMID- 26670474 TI - Preserved effector functions of human ORAI1- and STIM1-deficient neutrophils. PMID- 26670475 TI - Reliability and construct validity of a revised Baycrest Multiple Errands Test. AB - Surprisingly few ecologically-valid assessments of executive function exist, but the Baycrest Multiple Errands Test (BMET) shows promise in identifying executive impairment. The goal of the present study was to develop both a revised version of the assessment (BMET-R), to improve the test's ability to discriminate between patients and healthy participants, and an alternate form of the BMET-R to permit repeat testing. Sixteen individuals with acquired brain injury (ABI) due to stroke or trauma and 16 healthy participants completed a series of neuropsychological assessments, questionnaires, the BMET-R and its alternate form (in counterbalanced order). The results of the study indicated that participants with ABI omitted more tasks, broke more rules, and were less efficient than healthy participants on both the revised BMET-R and its alternate form. Moreover, significant correlations were found between the two versions of the BMET-R for task completions, omissions, errors, rule breaks and inefficiencies but few significant correlations were observed between the BMET-R versions and measures of executive dysfunction in everyday life. These results indicate that the two versions of the BMET-R are able to dissociate the performance of participants with ABI from that of healthy participants. However, despite overlaps in performance and correlations between the two versions of the BMET-R, they did not identically assess executive deficits. This suggests that caution should be used when constructing and validating alternate versions of performance-based assessments. PMID- 26670476 TI - Community pharmacy-based A1c screening: a Canadian model for diabetes care. AB - OBJECTIVES: Point-of-care HbA1c screening devices are a valuable tool that community pharmacists can use to monitor patients with diabetes and improve their overall management. We previously reported our experiences using these devices to assess glycaemic control in diabetic patients at three community pharmacy locations in Toronto, Ontario. Here, we report data from screening of over 1000 patients at clinics held across Canada. METHODS: Community pharmacies across Canada offering A1c screening as part of their professional programmes were invited to upload screening data to a central database. A1c analysis was performed using the Bayer A1c Now. Patient recruitment and approach to A1c screening were at the discretion of the participating pharmacies and were not standardized. Data collection took place over a period of 8 months. KEY FINDINGS: The majority of patients screened (59.1%) had A1c values above target, indicating inadequate glycaemic control. Glycaemic control was generally poorer among patients on more intensive treatment regimens. A total of 1711 clinical interventions were performed by pharmacists. An average of two interventions were performed per patient, and we observed a trend towards increased numbers of interventions in patients with poorer glycaemic control. The prevalence of specific types of interventions showed an apparent shift from predominantly pharmacist-directed interventions in patients with better glycaemic control towards an increased prevalence of physician-directed interventions in patients with poorer glycaemic control. CONCLUSIONS: These results illustrate the prevalence of suboptimal glycaemic control among diabetic patients in the community, which represents a significant opportunity for pharmacists to use point-of-care screening to detect hyperglycaemia and intervene to improve disease management when warranted. PMID- 26670477 TI - Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma. AB - PURPOSE: Histological response assessment following neoadjuvant treatment can help identify patients at a higher risk for systemic disease progression. Our goal was to evaluate whether mitotic count and the amount of viable tumour following neoadjuvant isolated limb perfusion (ILP) for primary, locally advanced, non-metastatic, high-grade extremity soft tissue sarcoma correlate with prognosis. PATIENTS AND METHODS: This study is a retrospective analysis of 61 patients who underwent neoadjuvant ILP followed by surgical resection with curative intent between 2001 and 2011. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median follow-up was 44 months for all patients and 55 months for survivors. The amount of viable tumour after ILP had no correlation with overall (OS) (P = 0.227) or event-free (EFS) (P = 0.238) survival probability. Patients with a low mitotic count after ILP had a significantly higher OS (P < 0.001), EFS (P = 0.002) and post-relapse survival probability (P = 0.030) compared to patients with an intermediate or high mitotic count. CONCLUSIONS: The mitotic count following ILP for primary, high-grade, locally advanced, non-metastatic soft tissue sarcoma appears to significantly correlate with prognosis. If these results are validated in a prospective setting, they could provide a rationale for the design of adjuvant systemic chemotherapy trials with the goal of improving the prognosis of patients with an intermediate or high mitotic count after ILP. PMID- 26670478 TI - Aberrant keratin 7 and 20 expression in triple-negative carcinoma of the breast. AB - Early studies characterizing the keratin (K) profile of various epithelial tissues indicated that breast carcinoma is K7 positive and K20 negative, but not all breast carcinomas show this profile. Triple-negative carcinoma (TNC) has been characterized by negativity for estrogen receptor (ER), progesterone receptor (PgR), and Her2/neu protein. TNC is more likely to metastasize to the viscera and present as a metastatic poorly different carcinoma. In our study, on the basis of immunohistochemical staining of ER, PgR, and Her2/neu, 75 of the 290 patients with invasive breast carcinoma were judged to have TNC. K20 expression was detected in 6 of 75 patients with TNC, and non-TNC was negative in all 215 cases (P = .0003). K7 expression was also detected in 72 of 75 TNC cases. However, non TNC was negative in 26 of 215 cases, which was significant (P = .0457). An aberrant profile of K was observed in the TNC group, indicating that caution is needed in determining the site of primary tumors using immunohistochemical algorithms. It should be kept in mind that patients with TNC show highly variable K profiles in practical diagnosis. PMID- 26670479 TI - Relationship between insulin sensitivity and insulin secretion rate: not necessarily hyperbolic. AB - AIMS: There is general acceptance that the physiological relationship between insulin sensitivity and insulin secretion is hyperbolic. This conclusion has evolved from studies in which one test assessed both variables, and changes in plasma insulin concentration were used as a surrogate measure for insulin secretion rate. The aim of this study was to see if a hyperbolic relationship would also emerge when separate and direct measures were used to quantify both insulin sensitivity and insulin secretion rate. METHODS: Steady-state plasma glucose (SSPG) was determined in 146 individuals without diabetes using the insulin suppression test, with 1/SSPG used to quantify insulin sensitivity. The graded-glucose infusion test was used to quantify insulin secretion rate. Plasma glucose and insulin concentrations obtained during an oral glucose tolerance test (OGTT) were used to calculate surrogate estimates of insulin action and insulin secretion rate. A hyperbolic relationship was assumed if the beta coefficient was near -1 using the following model: log (insulin secretion measure) = constant + beta * log (insulin sensitivity measure). RESULTS: OGTT calculations of insulin sensitivity (Matsuda) and plasma insulin response [ratio of insulin/glucose area under-the-curve (AUC) or insulin total AUC] provided the expected hyperbolic relationship [beta = -0.95, 95% CI (-1.09, -0.82); -1.06 (-1.14, -0.98)]. Direct measurements of insulin sensitivity and insulin secretion rate did not yield the same curvilinear relationship [beta = -1.97 (-3.19, -1.36)]. CONCLUSIONS: These findings demonstrate that the physiological relationship between insulin sensitivity and insulin secretion rate is not necessarily hyperbolic, but will vary with the method(s) by which it is determined. PMID- 26670481 TI - An examination of two concentrate allocation strategies which are based on the early lactation milk yield of autumn calving Holstein Friesian cows. AB - The objective of this experiment was to compare the effects of two concentrate feeding strategies offered with a grass silage and maize silage diet on the dry matter (DM) intake, milk production (MP) and estimated energy balance of autumn calved dairy cows. Over a 2-year period, 180 autumn calving Holstein Friesian cows were examined. Within year, cows were blocked into three MP sub-groups (n=9) (high (HMP), medium (MMP) and low (LMP)) based on the average MP data from weeks 3 and 4 of lactation. Within a block cows were randomly assigned to one of two treatments (n=54), flat rate (FR) concentrate feeding or feed to yield (FY) based on MP sub-group. Cows on the FR treatment were offered a fixed rate of concentrate (5.5 kg DM/cow per day) irrespective of MP sub-group. In the FY treatment HMP, MMP and LMP cows were allocated 7.3, 5.5 and 3.7 kg DM of concentrate, respectively. The mean concentrate offered to the FR and FY treatments was the same. On the FR treatment there was no significant difference in total dry matter intake (TDMI, 17.3 kg) between MP sub-groups. In the FY treatment, however, the TDMI of HMP-FY was 2.2 kg greater than MMP-FY, and 4.5 kg greater than LMP-FY (15.2 kg DM). The milk yield of LMP-FR was 3.5 kg less than the mean of the HMP-FR and MMP-FR treatments (24.5 kg). The milk yield of the HMP FY treatment was 3.6 and 7.9 kg greater than the MMP-FY and LMP-FY treatments, respectively. The difference in MP between the HMP sub-groups was 2.6 kg, which translates to a response of 1.4 kg of milk per additional 1 kg of concentrate offered. There was no significant difference in MP between the two LMP sub groups; however, MP increased 0.8 kg per additional 1 kg of concentrate offered between cows on the LMP-FR and LMP-FY treatments. The estimated energy balance was positive for cows on the LMP-FR treatment, but negative for cows on the other treatments. The experiment highlights the variation within a herd in MP response to concentrate, as cows with a lower MP potential are less responsive to additional energy input than cows with a greater MP potential. Cows with a greater MP capacity did not substitute additional concentrate for the basal forage, which indicates an additional demand for energy based on ability of individual cows to produce milk. PMID- 26670482 TI - A single- versus double-layered closure technique for full-thickness lower eyelid defects: a comparative study. AB - PURPOSE: To compare a simplified, single-layered closure technique with a double layered closure technique in lower eyelid reconstruction following full-thickness pentagonal block excision. METHODS: We conducted a retrospective, non-randomized, interventional case-control study. Clinical data of consecutive patients treated with primary closure of a full-thickness lower eyelid defect between 2011 and 2014 were analysed. In group A, the defect was closed in one layer, using non absorbable polypropylene sutures. In group B, the defect was closed in two layers, using absorbable polyglactin acid sutures. In both techniques, we rarely used a grey line suture to adjust the eyelid margin. We assessed notching, wound dehiscence and other complications, as reported at 2 months after surgery. RESULTS: We included 188 eyelids from 186 patients. In group A, we included 82 eyelids and in group B 106 eyelids. We noted no difference in notching (p = 0.96) whilst wound dehiscence had not occurred in either group. Subcutaneous granuloma formation had been noted in 0 cases in group A, versus 4 in group B (p = 0.08). Mild redness of the scar was seen in 2 cases in group A, versus 5 in group B (p = 0.41). A grey line suture was placed in 6 cases in group A (7.3%), versus 4 cases in group B (3.8%; p = 0.28). CONCLUSION: Both single- and double-layered closure techniques are safe and effective methods for primary closure of full-thickness lower eyelid defects. In both techniques, a grey line suture was rarely required to adjust the eyelid margin. PMID- 26670483 TI - Alcohol intake and binge drinking among Italian adolescents: The role of drinking motives. AB - Binge drinking, a pattern associated with worse outcome, is becoming increasingly popular among youths, thus negatively impacting social life. To investigate drinking patterns and their underlying motives in Italian adolescents, the Alcohol Use Questionnaire and the Drinking Motive Questionnaire Revised Short Form were administered to 332 school-age teenagers (16-19 years; 139 girls, 193 boys) from a single Roman school, recruited at their classrooms through the intermediation of their teachers. Boys scored higher than girls on all drinking and binge measures. They also scored higher on the Enhancement, Social, and Conformity Drinking Motive Questionnaire-Revised Short Form subscales. Binge drinking scores positively correlated with gender, alcohol consumption, and with all Drinking Motive Questionnaire Revised Short Form subscales. In the two-step hierarchical model, Drinking Motive Questionnaire-Revised Short Form enhancement and conformity predicted alcohol use and Drinking Motive Questionnaire-Revised Short Form coping motives significantly predicted binge drinking. Binge drinking is prevalent among Italian adolescents, who mainly drink to enhance perceived positive effects of alcohol, conform to their social groups, and face their problems. Boys binge more than girls. PMID- 26670484 TI - Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes. AB - The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3beta and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn 3b binding sites and is directly transactivated by this transcription factor in cotransfection assays, whereas chromatin immunoprecipitation assays confirm that Brn-3b binds to this promoter in vivo. In addition, correlation between GLUT4 and Brn-3b in KO tissues or in C2C12 cells strongly supports a close association between Brn-3b levels and GLUT4 expression. Since Brn-3b is regulated by metabolites and insulin, this may provide a mechanism for controlling key genes that are required for normal metabolic processes in insulin-responsive tissues and its loss may contribute to abnormal glucose uptake. PMID- 26670486 TI - Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. AB - Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50-400 MUg/ml) or control BSA (100 MUg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-kappaB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs. PMID- 26670485 TI - CTRP3 deficiency reduces liver size and alters IL-6 and TGFbeta levels in obese mice. AB - C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFbeta1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. PMID- 26670487 TI - Metabolic phenotype and adipose and liver features in a high-fat Western diet induced mouse model of obesity-linked NAFLD. AB - nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFbeta gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression. PMID- 26670488 TI - IL-1beta inhibits beta-Klotho expression and FGF19 signaling in hepatocytes. AB - Fibroblast growth factor (FGF) 19 is a member of the FGF15/19 subfamily of FGFs that includes FGF15/19, FGF21, and FGF23. FGF19 has been shown to have profound effects on liver metabolism and regeneration. FGF19 binds to FGFR4 and its coreceptor beta-Klotho to activate intracellular kinases, including Erk1/2. Studies have shown that proinflammatory cytokines such as TNFalpha impair FGF21 signaling in adipose cells by repressing beta-Klotho expression. However, little is known about the effects of inflammation on the FGF19 pathway in the liver. In the present study, we found that lipopolysaccharide (LPS) inhibited beta-Klotho and Fgfr4 expression in livers in mice, whereas LPS had no effects on the two FGF19 receptors in Huh-7 and HepG2 cells. Of the three inflammatory cytokines TNFalpha, IL-1beta, and IL-6, IL-1beta drastically inhibited beta-Klotho expression, whereas TNFalpha and IL-6 had no or minor effects. None of the three cytokines had any effects on FGFR4 expression. IL-1beta directly inhibited beta Klotho transcription, and this inhibition required both the JNK and NF-kappaB pathways. In addition, IL-1beta inhibited FGF19-induced Erk1/2 activation and cell proliferation. These results suggest that inflammation and IL-1beta play an important role in regulating FGF19 signaling and function in the liver. PMID- 26670490 TI - Ultrathin fiber-taper coupling with nitrogen vacancy centers in nanodiamonds at cryogenic temperatures. AB - We demonstrate cooling of ultrathin fiber tapers coupled with nitrogen vacancy (NV) centers in nanodiamonds to cryogenic temperatures. Nanodiamonds containing multiple NV centers are deposited on the subwavelength 480-nm-diameter nanofiber region of fiber tapers. The fiber tapers are successfully cooled to 9 K using our home-built mounting holder and an optimized cooling speed. The fluorescence from the nanodiamond NV centers is efficiently channeled into a single guided mode and shows characteristic sharp zero-phonon lines (ZPLs) of both neutral and negatively charged NV centers. The present nanofiber/nanodiamond hybrid systems at cryogenic temperatures can be used as NV-based quantum information devices and for highly sensitive nanoscale magnetometry in a cryogenic environment. PMID- 26670489 TI - Exploring health practitioners' acceptability of a prospective semi-quantitative pfHRP2 device to define severe malaria in the Democratic Republic of Congo. AB - BACKGROUND: A rapid diagnostic tool is being developed to discern severely ill children with severe malaria from children who are ill with alternative febrile diseases but have coincidental peripheral blood parasitaemia. The device semi quantitatively measures plasma pfHRP2 and has the potential to reduce mortality in children with severe febrile illnesses by improving diagnosis. The aim of this study is to identify contributing and inhibiting factors that affect healthcare practitioners' acceptability of this prospective diagnostic device in a high malaria transmission setting in the Democratic Republic of Congo. METHODS: Data were collected qualitatively by conducting semi-structured interviews with a purposeful sample of health professionals in Kinshasa, capital of Democratic Republic of Congo. In total, 11 interviews were held with professionals at four different institutes. RESULTS: Four key findings emerged: (1) Congolese practitioners perceive the semi-quantitative pfHRP2 device as a welcome intervention as they recognize the limited reliability of their current diagnostic and therapeutic approaches to severe febrile illnesses; (2) compatibility of the semi-quantitative pfHRP2 device with clinical equipment and competences of Congolese health practitioners is considered to be limited, especially in rural settings; (3) a formal training programme is crucial for correct understanding and application of the semi-quantitative pfHRP2 device; and, (4) provision of evidence to practitioners, and support from health authorities would be important to establish confidence in the semi-quantitative pfHRP2 device. CONCLUSIONS: Congolese practitioners perceive the prospective semi quantitative pfHRP2 device as a welcome addition to their clinical equipment. The device could improve current diagnostic work-up of severe febrile illness, which might consequently improve treatment choices. However, despite this recognized potential, several hurdles and drivers need to be taken into account when implementing this device in DR Congo. PMID- 26670491 TI - Type IIa Bragg grating based ultra-short DBR fiber laser with high temperature resistance. AB - We report on the fabrication of a thermally resistant ultra-short distributed Bragg reflector (DBR) fiber laser based on the photo inscription of two wavelength-matched type IIa gratings in a thin-core Er-doped fiber. With continuous UV exposure, each Bragg reflector initially grows as a type I grating, followed by decay in strength, and then re-grows as a type IIa grating with enhanced thermal resistance. The DBR laser, with an entire length of 13 mm, can stably operate at 600 degrees C with single longitude mode, which provides potential applications in high temperature environments. PMID- 26670492 TI - Theoretical analysis and modeling of a photonic integrated circuit for frequency 8-tupled and 24-tupled millimeter wave signal generation: erratum. AB - A novel photonic circuit design for implementing frequency 8-tupling and 24 tupling was presented [Opt. Lett.39, 6950 (2014)10.1364/OL.39.006950OPLEDP0146 9592], and although its key message remains unaltered, there were typographical errors in the equations that are corrected in this erratum. PMID- 26670493 TI - Photoluminescence from voids created by femtosecond-laser pulses inside cubic-BN. AB - Photoluminescence (PL) from femtosecond-laser-modified regions inside cubic-boron nitride (c-BN) was measured under UV and visible light excitation. Bright PL at the red spectral range was observed, with a typical excited state lifetime of ~4 ns. Sharp emission lines are consistent with PL of intrinsic vibronic defects linked to the nitrogen vacancy formation (via Frenkel pair) observed earlier in high-energy electron-irradiated and ion-implanted c-BN. These, formerly known as the radiation centers, RC1, RC2, and RC3, have been identified at the locus of the voids formed by a single femtosecond-laser pulse. The method is promising to engineer color centers in c-BN for photonic applications. PMID- 26670494 TI - Necklace beam generation in nonlinear colloidal engineered media. AB - Modulational instability is a phenomenon that reveals itself as the exponential growth of weak perturbations in the presence of an intense pump beam propagating in a nonlinear medium. It plays a key role in such nonlinear optical processes as supercontinuum generation, light filamentation, rogue waves, and ring (or necklace) beam formation. To date, a majority of studies of these phenomena have focused on light-matter interactions in self-focusing Kerr media existing in nature. However, a large and tunable nonlinear response of a colloidal suspension can be tailored at will by judiciously engineering the optical polarizability. Here, we analytically and numerically show the possibility of necklace beam generation originating from spatial modulational instability of vortex beams in engineered soft-matter nonlinear media with different types of exponential nonlinearity. PMID- 26670495 TI - Raman linewidth measurements using time-resolved hybrid picosecond/nanosecond rotational CARS. AB - We report an innovative approach for time-domain measurements of S-branch Raman linewidths using hybrid picosecond/nanosecond pure-rotational coherent anti Stokes Raman spectroscopy (RCARS). The Raman coherences are created by two picosecond excitation pulses and are probed using a narrow-band nanosecond pulse at 532 nm. The generated RCARS signal contains the entire coherence decay in a single pulse. By extracting the decay times of the individual transitions, the J dependent Raman linewidths can be calculated. Self-broadened S-branch linewidths for nitrogen and oxygen at 293 K and ambient pressure are in good agreement with previous time-domain measurements. Experimental considerations of the approach are discussed along with its merits and limitations. The approach can be extended to a wide range of pressures and temperatures and has potential for simultaneous single-shot thermometry and linewidth determination. PMID- 26670496 TI - Model-based sensor-less wavefront aberration correction in optical coherence tomography. AB - Several sensor-less wavefront aberration correction methods that correct nonlinear wavefront aberrations by maximizing the optical coherence tomography (OCT) signal are tested on an OCT setup. A conventional coordinate search method is compared to two model-based optimization methods. The first model-based method takes advantage of the well-known optimization algorithm (NEWUOA) and utilizes a quadratic model. The second model-based method (DONE) is new and utilizes a random multidimensional Fourier-basis expansion. The model-based algorithms achieve lower wavefront errors with up to ten times fewer measurements. Furthermore, the newly proposed DONE method outperforms the NEWUOA method significantly. The DONE algorithm is tested on OCT images and shows a significantly improved image quality. PMID- 26670497 TI - Time-resolved shadowgraphs of transient plasma induced by spatiotemporally focused femtosecond laser pulses in fused silica glass. AB - We report on experimental observations of formation and evolution of transient plasma produced in fused silica glass with spatiotemporally focused (STF) femtosecond laser pulses using a pump-probe shadow imaging technique. Surprisingly, the observation shows that the track of the plasma is significantly curved, which is attributed to an asymmetric density distribution of the transient plasma produced in the focal volume caused by the pulse front tilt of the STF laser field. PMID- 26670498 TI - High-power, mid-infrared, picosecond pulses generated by compression of a CO2 laser beat-wave in GaAs. AB - We report on the generation of a train of ~2 ps, 10 MUm laser pulses via multiple four-wave mixing and compression of an infrared laser beat-wave propagating in the negative group velocity dispersion region of bulk GaAs and a combination of GaAs and NaCl crystals. The use of a 200 ps, 106 GHz beat-wave, produced by combining laser pulses amplified on the 10P(20) and 10P(16) transition of a CO2 laser, provides a novel method for generating high-power, picosecond, mid-IR laser pulses at a high repetition rate. By using 165 and 882 GHz beat-waves, we show that cascaded phase-mismatched difference frequency generation plays a significant role in the four-wave mixing process in GaAs. PMID- 26670499 TI - Femtosecond laser-induced surface structures on carbon fibers. AB - The influence of different polarization states during the generation of periodic nanostructures on the surface of carbon fibers was investigated using a femtosecond laser with a pulse duration tau=300 fs, a wavelength lambda=1025 nm, and a peak fluence F=4 J/cm2. It was shown that linear polarization results in a well-aligned periodic pattern with different orders of magnitude concerning their period and an alignment parallel and perpendicular to fiber direction, respectively. For circular polarization, both types of uniform laser-induced periodic surface structures (LIPSS) patterns appear simultaneously with different dominance in dependence on the position at the fiber surface. Their orientation was explained by the polarization-dependent absorptivity and the geometrical anisotropy of the carbon fibers. PMID- 26670500 TI - Revealing the photophysics of gold-nanobeacons via time-resolved fluorescence spectroscopy. AB - We demonstrate that time-resolved fluorescence spectroscopy is a powerful tool to investigate the conformation states of hairpin DNA on the surface of gold nanoparticles (AuNPs) and energy transfer processes in Au-nanobeacons. Long-range fluorescence quenching of Cy5 by AuNPs has been found to be in good agreement with electrodynamics modeling. Moreover, time-correlated single-photon counting (TCSPC) is shown to be promising for real-time monitoring of the hybridization kinetics of Au-nanobeacons, with up to 60% increase in decay time component and 300% increase in component fluorescence fraction observed. Our results also indicate the importance of the stem and spacer designs for the performance of Au nanobeacons. PMID- 26670502 TI - Resonant evanescent complex fields on dielectric multilayers. AB - Complex light fields, including evanescent Bessel beams, can be generated at dielectric interfaces by means of oil-immersion optics operating in total internal reflection conditions. Here we report on the observation of evanescent complex fields produced on a dielectric multilayer through the interference of surface modes resonantly sustained by the multilayer itself. The coupling to surface modes is attained by modifying the wavefront of an incident laser beam in such a way that the resulting intensity distribution in k-space matches the dispersion of the surface mode. The phase of surface modes can be further controlled, and two-dimensional vortex beams can also be produced according to the same working principle. PMID- 26670501 TI - Dual accelerating Airy-Talbot recurrence effect. AB - We demonstrate the dual accelerating Airy-Talbot recurrence effect, i.e., the self-imaging of accelerating optical beams, by propagating a superposition of Airy beams with successively changing transverse displacements. The dual Airy Talbot effect is a spontaneous recurring imaging of the input and of the input with alternating component signs. It results from the constructive interference of Airy wave functions, which is also responsible for other kinds of Airy beams, for example, Airy breathers. An input composed of finite-energy Airy beams also displays the dual Airy-Talbot effect, but it demands a large transverse displacement and diminishes fast along the propagation direction. PMID- 26670503 TI - Metamaterial-waveguide bends with effective bend radius < lambda0/2. AB - We designed, fabricated, and characterized broadband, efficient, all-dielectric metamaterial-waveguide bends (MWBs) that redirect light by 180 deg. The footprint of each MWB is 3 MUm*3 MUm and redirection is achieved for single-mode waveguides spaced by 1.3 MUm, which corresponds to an effective bend radius of 0.65 MUm (80% and ~70%, respectively. Furthermore, the MWBs have an operating bandwidth >66 nm (design) and >56 nm (experiments). Our design methodology that incorporates fabrication constraints enables highly robust devices. The methodology can be extended to the general routing of light in tight spaces for large-scale photonic integration. PMID- 26670504 TI - Confocal microscopy through a multimode fiber using optical correlation. AB - We report on a method to obtain confocal imaging through multimode fibers using optical correlation. First, we measure the fiber's transmission matrix in a calibration step. This allows us to create focused spots at one end of the fiber by shaping the wavefront sent into it from the opposite end. These spots are scanned over a sample, and the light returning from the sample via the fiber is optically correlated with the input pattern. We show that this achieves spatial selectivity in the detection. The technique is demonstrated on microbeads, a dried epithelial cell, and a cover glass. PMID- 26670505 TI - Radially polarized emission with 635 W of average power and 2.1 mJ of pulse energy generated by an ultrafast thin-disk multipass amplifier. AB - We report on a thin-disk multipass amplifier delivering radially polarized laser pulses with an average power of 635 W and 2.1 mJ of pulse energy. To the best of our knowledge, this is the highest average output power and pulse energy reported so far for radially polarized ultrafast lasers. The amplifier is seeded by a TruMicro5050 with 115 W of average output power, 6.5 ps pulse duration, and a repetition rate of 300 kHz. A segmented half-waveplate was used for converting the linearly polarized beam into radial polarization in front of the amplifier. We present a scheme for direct amplification of such doughnut-shaped radially polarized beams, the results obtained, and a solution to compensate for the depolarizing phase shift introduced by the tilted mirrors in the amplifier. PMID- 26670506 TI - Efficient narrowband terahertz generation in cryogenically cooled periodically poled lithium niobate. AB - We present an efficiency scaling study of optical rectification in cryogenically cooled periodically poled lithium niobate for the generation of narrowband terahertz radiation using ultrashort pulses. The results show an efficiency and brilliance increase compared to previous schemes of up to 2 orders of magnitude by exploring the optimal pump pulse format at around 800 nm, and reveal saturation mechanisms limiting the conversion efficiency. We achieve >10-3 energy conversion efficiencies, MUJ-level energies, and bandwidths <20 GHz at ~0.5 THz, thereby showing unprecedented spectral brightness in the 0.1-1 THz range relevant to terahertz science and technology. PMID- 26670507 TI - Ultrahigh quality factor in a metal-embedded semiconductor microdisk cavity. AB - We numerically and theoretically investigate electrodynamics of a metal-embedded semiconductor microdisk cavity. The electrodynamics of a cavity mode is discussed from the viewpoint of quantum mechanics, which clarifies the condition for high Q factor. Using numerical calculations, we optimize the cavity structure and show that the Q factor can be increased up to 1,700,000. Our study suggests that the metal-embedded cavity is a promising candidate for cavity quantum electrodynamics (QED) devices. PMID- 26670508 TI - Ultrabroadband ghost imaging exploiting optoelectronic amplified spontaneous emission and two-photon detection. AB - Ghost imaging (GI) is one of the recent fascinating and probably counterintuitive topics of quantum optics. Here, we present an alternative classical GI scheme using spectrally ultrabroadband amplified spontaneous emission from an optoelectronic quantum dot based superluminescent diode source. This light source exhibits highly incoherent properties regarding both first- and second-order correlations with a 70 nm-wide optical spectrum as well as thermal-like photon statistics. Exploiting a two-photon-absorption detection method, we demonstrate for the first time, to the best of our knowledge, a GI experiment handling the corresponding femtosecond correlation timescales. By introducing compact broadband light sources to GI, this work contributes toward practical application of GI. PMID- 26670509 TI - Broadband high-power mid-IR femtosecond pulse generation from an ytterbium-doped fiber laser pumped optical parametric amplifier. AB - We report on a high-power periodically poled MgO-doped lithium niobate (MgO:PPLN) based femtosecond optical parametric amplifier (OPA), featuring a spectral seamless broadband mid-infrared (MIR) output. By modifying the initial chirp and spectrum of the mode-locked seed laser, the Yb fiber pump laser exhibits a final output power of 14 W with sub-200-fs pulse duration after power amplification and compression. When the OPA was seeded with a broadband amplified spontaneous emission (ASE) source, a damage-limited 0.6 W broadband MIR radiation was experimentally obtained under the pump power of 10.15 W at 82 MHz repetition rate, corresponding to an overall OPA conversion efficiency of 32.7%. The 3 dB bandwidth of the mid-IR idler was 291.9 nm, centering at 3.34 MUm. PMID- 26670510 TI - Self-mixing in low-noise semiconductor vortex laser: detection of a rotational Doppler shift in backscattered light. AB - Light carrying orbital angular momentum L?, scattered by a rotating object at angular velocity Omega?, experiences a rotational Doppler shift Omega?.L?. We show that this fundamental light-matter interaction can be detected exploiting self-mixing in a vortex laser under Doppler-shifted optical feedback, with quantum noise-limited light detection. We used a low-noise relaxation oscillation free (class-A) vortex laser, based on III-V semiconductor vertical-external cavity-surface-emitting laser technology to generate coherent Laguerre-Gauss beams carrying L=hl (l=+/-1,...+/-4). Linear and rotational Doppler effects were studied experimentally and theoretically. This will allow us to combine a velocity sensor with optical tweezers for micro-manipulation applications, with high performances: compact, powerful ?10 mW, high-quality beam, auto-aligned, linear response up to >108 rad/s or >300 km/h, low back-scattered light detection limit <10-16/Hz. PMID- 26670511 TI - Simultaneous optical coherence tomography angiography and fluorescein angiography in rodents with normal retina and laser-induced choroidal neovascularization. AB - Fluorescein angiography (FA) is the current clinical imaging standard for vascular related retinal diseases such as macular degeneration and diabetic retinopathy. However, FA is considered invasive and can provide only two dimensional imaging. In comparison, optical coherence tomography angiography (OCTA) is noninvasive and can generate three-dimensional imaging; investigations of OCTA already demonstrated great promise in retinal vascular imaging. Yet, to further develop and apply OCTA, strengths and weaknesses between OCTA and FA need to be thoroughly compared. To avoid complications in image registration, an ideal comparison requires co-registered and simultaneous imaging by both FA and OCTA. In this Letter, we developed a system with integrated laser-scanning ophthalmoscope FA (SLO-FA) and OCTA, and conducted simultaneous dual-modality retinal vascular imaging in rodents. In imaging healthy rodent eyes, OCTA can resolve retinal capillaries better than SLO-FA does, particularly deep capillaries. In imaging rodent eyes with laser-induced choroidal neovascularization (CNV), OCTA can identify CNV that eludes SLO-FA detection. PMID- 26670512 TI - Photothermal speckle modulation for noncontact materials characterization. AB - We have developed a noncontact, photothermal materials characterization method based on visible-light speckle imaging. This technique is applied to remotely measure the infrared absorption spectra of materials and to discriminate materials based on their thermal conductivities. A wavelength-tunable (7.5-8.7 MUm), intensity-modulated, quantum cascade pump laser and a continuous-wave 532 nm probe laser illuminate a sample surface such that the two laser spots overlap. Surface absorption of the intensity-modulated pump laser induces a time-varying thermoelastic surface deformation, resulting in a time-varying 532 nm scattering speckle field from the surface. The speckle modulation amplitude, derived from a series of visible camera images, is found to correlate with the amplitude of the surface motion. By tuning the pump laser's wavelength over a molecular absorption feature, the amplitude spectrum of the speckle modulation is found to correlate to the IR absorption spectrum. As an example, we demonstrate this technique for spectroscopic identification of thin polymeric films. Furthermore, by adjusting the rate of modulation of the pump beam and measuring the associated modulation transfer to the visible speckle pattern, information about the thermal time constants of surface and sub-surface features can be revealed. Using this approach, we demonstrate the ability to distinguish between different materials (including metals, semiconductors, and insulators) based on differences in their thermal conductivities. PMID- 26670513 TI - Semianalytical quasi-normal mode theory for the local density of states in coupled photonic crystal cavity-waveguide structures. AB - We present and validate a semianalytical quasi-normal mode (QNM) theory for the local density of states (LDOS) in coupled photonic crystal (PhC) cavity-waveguide structures. By means of an expansion of the Green's function on one or a few QNMs, a closed-form expression for the LDOS is obtained, and for two types of two dimensional PhCs, with one and two cavities side-coupled to an extended waveguide, the theory is validated against numerically exact computations. For the single cavity, a slightly asymmetric spectrum is found, which the QNM theory reproduces, and for two cavities, a nontrivial spectrum with a peak and a dip is found, which is reproduced only when including both the two relevant QNMs in the theory. In both cases, we find relative errors below 1% in the bandwidth of interest. PMID- 26670514 TI - Measurement of the nonlinear refractive index of air constituents at mid-infrared wavelengths. AB - We measure the nonlinear refractive index coefficients in N2, O2, and Ar from visible through mid-infrared wavelengths (lambda=0.4-2.4 MUm). The wavelengths investigated correspond to transparency windows in the atmosphere. Good agreement is found with theoretical models of chi((3)). Our results are essential for accurately simulating the propagation of ultrashort mid-infrared pulses in the atmosphere. PMID- 26670515 TI - AuAg bimetallic nonalloyed nanoparticles on a periodically nanostructured GaAs substrate for enhancing light trapping. AB - We present a light trapping structure consisting of AuAg bimetallic nonalloyed nanoparticles (BNNPs) on cone-shaped GaAs subwavelength structures (SWSs), combining the advantages of plasmonic structures and SWSs for GaAs-based solar cell applications. To obtain efficient light trapping in solar cells, the optical properties' dependence on the size and composition of the Ag and Au metal nanoparticles was systematically investigated. Cone-shaped GaAs SWSs with AuAg BNNPs formed from an Au film of 12 nm and an Ag film of 10 nm exhibited the extremely low average reflectance (R(avg)) of 2.43% and the solar-weighted reflectance (SWR) of 2.38%, compared to that of a bare GaAs substrate (R(avg), 37.50%; SWR, 36.72%) in the wavelength range of 300 to 870 nm. PMID- 26670516 TI - Generation of five phase-locked harmonics by implementing a divide-by-three optical frequency divider. AB - We report the generation of five phase-locked harmonics, f1:2403 nm, f2:1201 nm, f3:801 nm, f4:600 nm, and f5:480 nm with an exact frequency ratio of 1:2:3:4:5 by implementing a divide-by-three optical frequency divider in the high harmonic generation process. All five harmonics are generated coaxially with high phase coherence in time and space, which are applicable for various practical uses. PMID- 26670517 TI - PT-symmetric phase in kagome-based photonic lattices. AB - The kagome lattice is a two-dimensional network of corner-sharing triangles and is often associated with geometrical frustration. In particular, the frustrated coupling between waveguide modes in a kagome array leads to a dispersionless flat band consisting of spatially localized modes. Here we propose a complex photonic lattice by placing PT-symmetric dimers at the kagome lattice points. Each dimer corresponds to a pair of strongly coupled waveguides. With balanced arrangement of gain and loss on individual dimers, the system exhibits a PT-symmetric phase for finite gain/loss parameter up to a critical value. The beam evolution in this complex kagome waveguide array exhibits a novel oscillatory rotation of optical power along the propagation distance. Long-lived local chiral structures originating from the nearly flat bands of the kagome structure are observed when the lattice is subject to a narrow beam excitation. PMID- 26670518 TI - Experimental demonstration of 20 Gbit/s data encoding and 2 ns channel hopping using orbital angular momentum modes. AB - We explore the use of the spatial domain as a degree of freedom for data encoding and channel hopping. We experimentally demonstrate data encoding at 20 Gbit/s using four possible orbital angular momentum (OAM) modes. The influence of mode spacing and time misalignment between modal channels on the switching crosstalk and bit-error rates is investigated. We find that the use of adjacent modes with a mode spacing of one introduces an extra power penalty of 3.2 dB compared with a larger mode spacing. Moreover, we demonstrate reconfigurable hopping of a 100 Gbit/s quadrature-phase-shift-keying (QPSK) data channel between four OAM modes with a 2 ns switching guard time. The results show that the power penalties for different hopping rates and mode spacings are less than 5.3 dB. PMID- 26670519 TI - Efficient broadband light absorption in elliptical nanohole arrays for photovoltaic application. AB - We propose a perpendicular elliptical silicon nanohole (PE-SiNH) array for light absorption in thin film silicon solar cells. Our analysis shows that this architecture is capable of increasing the absorption of a thin film silicon solar cell by 11.3% in comparison to that of the optimal circular SiNH array. The process of breaking the mirror symmetries is responsible for the increase of the coupled modes. The PE-SiNH structures show additional near-zero spatial Fourier components compared with the circular SiNH structure, which helps to couple more incident light into slow Bloch modes. The mode interaction between adjacent elliptical nanoholes is in favor of the coupling of the incident light into channeling modes and, therefore, enhances light absorption in the short wavelength region. PMID- 26670520 TI - 3D laser-written silica glass step-index high-contrast waveguides for the 3.5 MUm mid-infrared range. AB - We report on the direct laser fabrication of step-index waveguides in fused silica substrates for operation in the 3.5 MUm mid-infrared wavelength range. We demonstrate core-cladding index contrasts of 0.7% at 3.39 MUm and propagation losses of 1.3 (6.5) dB/cm at 3.39 (3.68) MUm, close to the intrinsic losses of the glass. We also report on the existence of three different laser modified SiO2 glass volumes, their different micro-Raman spectra, and their different temperature-dependent populations of color centers, tentatively clarifying the SiO2 lattice changes that are related to the large index changes. PMID- 26670521 TI - Terahertz far-field superresolution imaging through spoof surface plasmons illumination. AB - The applications of terahertz (THz) imaging are always restricted by the low resolution. We introduce here a new way to realize far-field superresolution imaging at THz frequency. Assisted by a new spoof surface plasmons (SSP) probe illumination, the images of two subwavelength separated slits can be reconstructed by a single shot. Although only 0.06lambda resolution is numerically demonstrated at 0.3 THz, the resolution potentially can be further enhanced by scaling down the size of the SSP probe. Deep subwavelength focusing is also achieved by the SSP probe. Our work may open a new avenue for SSP-based superresolution at longer wavelengths. PMID- 26670522 TI - Beam scanning for rapid coherent Raman hyperspectral imaging. AB - Coherent Raman imaging requires high-peak power laser pulses to maximize the nonlinear multiphoton signal generation, but accompanying photo-induced sample damage often poses a challenge to microscopic imaging studies. We demonstrate that beam scanning by a 3.5-kHz resonant mirror in a broadband coherent anti Stokes Raman scattering (BCARS) imaging system can reduce photo-induced damage without compromising signal intensity. Additionally, beam scanning enables slit acquisition, in which spectra from a thin line of sample illumination are acquired in parallel during a single charge-coupled device exposure. Reflective mirrors are employed in the beam-scanning assembly to minimize chromatic aberration and temporal dispersion. The combined approach of beam scanning and slit acquisition is compared with the sample-scanning mode in terms of spatial resolution, photo-induced damage, and imaging speed at the maximum laser power below the sample-damage threshold. We show that the beam-scanning BCARS imaging method can reduce photodamage probability in biological cells and tissues, enabling faster imaging speed by using a higher excitation laser power than could be achieved without beam scanning. PMID- 26670523 TI - Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO. AB - Scanning laser ophthalmoscopy (SLO) employs the eye's optics as a microscope objective for retinal imaging in vivo. The mouse retina has become an increasingly important object for investigation of ocular disease and physiology with optogenetic probes. SLO imaging of the mouse eye, in principle, can achieve submicron lateral resolution thanks to a numerical aperture (NA) of ~0.5, about 2.5 times larger than that of the human eye. In the absence of adaptive optics, however, natural ocular aberrations limit the available optical resolution. The use of a contact lens, in principle, can correct many aberrations, permitting the use of a wider scanning beam and, thus, achieving greater resolution then would otherwise be possible. In this Letter, using an SLO equipped with a rigid contact lens, we report the effect of scanning beam size on the lateral resolution of mouse retinal imaging. Theory predicts that the maximum beam size full width at half-maximum (FWHM) that can be used without any deteriorating effects of aberrations is ~0.6 mm. However, increasing the beam size up to the diameter of the dilated pupil is predicted to improve lateral resolution, though not to the diffraction limit. To test these predictions, the dendrites of a retinal ganglion cell expressing YFP were imaged, and transverse scans were analyzed to quantify the SLO system resolution. The results confirmed that lateral resolution increases with the beam size as predicted. With a 1.3 mm scanning beam and no high-order aberration correction, the lateral resolution is ~1.15 MUm, superior to that achievable by most human AO-SLO systems. Advantages of this approach include stabilization of the mouse eye and simplified optical design. PMID- 26670524 TI - Production of dynamic frozen waves: controlling shape, location (and speed) of diffraction-resistant beams. AB - In recent times, we experimentally realized quite an efficient modeling of the shape of diffraction-resistant optical beams, thus generating for the first time the so-called frozen waves (FW), whose longitudinal intensity pattern can be arbitrarily chosen within a prefixed space interval of the propagation axis. In this Letter, we extend our theory of FWs, which led to beams endowed with a static envelope, through a dynamic modeling of the FWs whose shape is now allowed to evolve in time in a predetermined way. Further, we experimentally create such dynamic FWs (DFWs) in optics via a computational holographic technique and a spatial light modulator. Experimental results are presented here for two cases of DFWs, one of zeroth order and the other of higher order, the latter being the most interesting exhibiting a cylindrical surface of light whose geometry changes in space and time. PMID- 26670525 TI - Enhanced light extraction efficiency in organic light-emitting diode with randomly dispersed nanopattern. AB - An optical scattering layer composed of randomly dispersed nanopatterns (RDNPs) was introduced in an organic light-emitting diode (OLED) to increase the out coupling efficiency. An RDNP was fabricated by direct printing on a glass substrate. Owing to its low haze and high transmittance, the RDNP acted as a light extraction layer in the OLED. The RDNP OLEDs showed higher current density and luminance than the reference devices at the same voltage. The current and power efficiencies of the RDNP OLED increased by 25% and 34%, respectively, without electrical degradation. Furthermore, the RDNP devices achieved an external quantum efficiency of 27.5% at 1 mA/cm2. PMID- 26670526 TI - Strong coupling of hybrid and plasmonic resonances in liquid core plasmonic micro bubble cavities. AB - A thin-wall plasmonic micro-bubble resonator, which is a high-Q optofluidic silica bubble cavity with a thin Ag film on the inside wall of the bubble, is proposed and fabricated to manipulate coupling among various types of resonant modes by changing its wall thickness and refractive index of the liquid in the core. Coupling of high-Q whispering gallery mode/plasmonic resonant mode forms hybrid mode; the hybrid mode can again strongly couple with another interior plasmonic resonant mode in the bubble cavity to achieve tunable high-Q plasmonic resonance that can be feasibly accessed by standard tapered fiber coupling. Therefore, the novel cavity structure provides a unique, yet general, platform to study plasmonic/photonic, hybrid/plasmonic, and plasmonic/plasmonic coupling. PMID- 26670527 TI - Design of eight-mode polarization-maintaining few-mode fiber for multiple-input multiple-output-free spatial division multiplexing. AB - We propose a polarization-maintaining few-mode fiber (FMF) that features an elliptical ring shaped core with a high refractive index contrast ~0.03 between the core and the cladding. This fiber design alleviates the usual trade-off between the number of guided modes and the achievable birefringence that is usually observed in conventional elliptical-core FMFs. Through numerical simulations, we show that this fiber design can support up to 10 guided vector modes over the entire C band while providing large birefringence. Except for the two fundamental modes, the eight higher-order vector modes are all separated from their adjacent modes by effective index differences >10-4, which is the typical birefringence value of single-mode polarization maintaining fibers. The designed fiber targets applications in spatial division multiplexing of optical channels, without multiple-input-multiple-output (MIMO) digital signal processing, for short-reach optical interconnects. PMID- 26670528 TI - Radial smoothing for improving laser-beam irradiance uniformity. AB - Laser-beam irradiation uniformity is a key issue in inertial confinement fusion research. We propose a radial smoothing (RS) approach in which the speckle in a focal plane is smoothed by the radial redistribution through fast focal zooming. This focal zooming is generated by introducing the periodical spherical wavefront modulation to the laser beam, based on an optical Kerr medium and its pump laser with the temporal profile of a Gaussian pulse train. The utilization of RS significantly improves the laser-beam uniformity without obvious impact on the performance of the high-power laser system. PMID- 26670529 TI - Gigabit Ethernet signal transmission using asynchronous optical code division multiple access. AB - We propose and experimentally demonstrate a novel architecture for interfacing and transmitting a Gigabit Ethernet (GbE) signal using asynchronous incoherent optical code division multiple access (OCDMA). This is the first such asynchronous incoherent OCDMA system carrying GbE data being demonstrated to be working among multi-users where each user is operating with an independent clock/data rate and is granted random access to the network. Three major components, the GbE interface, the OCDMA transmitter, and the OCDMA receiver are discussed in detail. The performance of the system is studied and characterized through measuring eye diagrams, bit-error rate and packet loss rate in real-time file transfer. Our Letter also addresses the near-far problem and realizes asynchronous transmission and detection of signal. PMID- 26670530 TI - Broadband and wide-range feedback tuning scheme for phase-locked loop stabilization of tunable optoelectronic oscillators. AB - In this Letter, we propose and experimentally demonstrate a novel broadband and wide-range feedback tuning scheme for phase-locked loop (PLL) stabilization of tunable optoelectronic oscillators (OEO). The proposed scheme was realized in a simple and feasible way based on a dual-parallel Mach-Zehnder modulator (DPMZM) and optical bandpass filter (OBPF). The wide RF phase-shift range and broadband performance of the proposed scheme were demonstrated theoretically and experimentally, which ensured OEO's wide operating temperature range and tunability in PLL stabilization. As a result, PLL stabilization for OEO was achieved at different oscillating frequencies and the long-term stability was greatly improved without any thermal control. The measured overlapping Allan deviation of PLL-locked OEO reached lower than 10-10 after 1000-s averaging time, which was four orders of magnitude better than the free-running OEO. The phase noise performance was also improved at low-offset frequencies and remained the same at high-offset frequencies. PMID- 26670531 TI - Resonant micro-optic gyro using a short and high-finesse fiber ring resonator. AB - A novel hybrid integrated scheme is proposed for a high-performance resonant micro-optic gyro (RMOG), which requires a low-loss micro-ring resonator for mass production. A new record for the RMOG is established experimentally with a short fiber ring resonator and an integrated signal detecting and processing circuit. The finesse of the short fiber ring resonator with a length of 60 cm and a diameter of 4.77 cm is as high as 202, and the theoretical sensitivity of the RMOG is better than 0.3 degrees /h assuming the average optical intensity at the photodetector is 1 mW. The 60 cm long spliceless micro-ring resonator is experimentally proved to be sufficient for a tactical-grade RMOG. An angle random walk coefficient of 0.64 degrees /?h and a typical bias stability below 9.6 degrees /h for the integration time of 50 s are successfully demonstrated using an innovative open-loop approach for an operation time of 1600 s. PMID- 26670532 TI - High-energy-density, all-solid-state microsupercapacitors with three-dimensional interdigital electrodes of carbon/polymer electrolyte composite. AB - Novel all-solid-state microsupercapacitors (MSCs) with three-dimensional (3D) electrodes consisting of active materials (i.e., graphene or activated carbon (AC) particles) and polymer electrolyte (PE) designed for high-energy-density storage applications were fabricated and tested in this work. The incorporation of PE in the electrode material enhances the accessibility of electrolyte ions to the surface of active materials and decreases the ion diffusion path during electrochemical charge/discharge. For a scan rate of 5 mV s(-1), the MSCs with graphene/PE and AC/PE composite electrodes demonstrate a very high areal capacitance of 95 and 134 mF cm(-2), respectively, comparable to that of 3D MSCs with liquid electrolyte. In addition, the graphene/PE MSCs show a ~70% increase in specific capacitance after 10 000 charge/discharge cycles, attributed to an electro-activation process resulting from ion intercalation between the graphene nanosheets. The AC/PE MSCs also demonstrate excellent stability. The results of this study illustrate the potential of the present 3D MSCs for various high density solid-state energy storage applications. PMID- 26670542 TI - Incidence and prevalence of autoimmune hepatitis in the Ueda area, Japan. AB - AIM: Although autoimmune hepatitis (AIH) is considered to be rare in Japan, precise data on the incidence and prevalence of this disease are scarce due to the lack of a nationwide registry. We therefore conducted a study of these factors over a secondary medical care area. METHODS: We retrospectively investigated the medical records of AIH patients seen during 2004-2009 and prospectively recruited subjects from 2010 to 2014 at our hospital. We surveyed via written questionnaires to all family doctors and hospitals in our secondary medical care area of Ueda, with a population 187 205 individuals over 14 years of age. We also surveyed several core liver disease hospitals in the areas neighboring Ueda. RESULTS: Forty-eight patients with AIH were diagnosed between 2004 and 2014. AIH with histological features of acute hepatitis was increased. The average annual incidence of AIH in the area was 2.23 (age-standardized to the Japanese population). Forty-eight patients (37 patients diagnosed between 2004 and 2014, and 11 patients before 2003) were followed to the study end-point. The prevalence was 23.4 (age-standardized to the Japanese population) on 31 December 2014. After age-standardization to the World Health Organization world standard population, the incidence and prevalence of AIH decreased to 1.52 and 15.0, respectively, likely due to the high proportion of elderly patients in Japan. CONCLUSION: The incidence and prevalence of AIH in Japan may be higher than previously believed due to increased awareness among family doctors, and a rise in the diagnosis of mild or atypical AIH. PMID- 26670543 TI - Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments. AB - The endosomal sorting complexes required for transport (ESCRTs) constitute hetero oligomeric machines that catalyze multiple topologically similar membrane remodeling processes. Although ESCRT-III subunits polymerize into spirals, how individual ESCRT-III subunits are activated and assembled together into a membrane-deforming filament remains unknown. Here, we determine X-ray crystal structures of the most abundant ESCRT-III subunit Snf7 in its active conformation. Using pulsed dipolar electron spin resonance spectroscopy (PDS), we show that Snf7 activation requires a prominent conformational rearrangement to expose protein-membrane and protein-protein interfaces. This promotes the assembly of Snf7 arrays with ~30 A periodicity into a membrane-sculpting filament. Using a combination of biochemical and genetic approaches, both in vitro and in vivo, we demonstrate that mutations on these protein interfaces halt Snf7 assembly and block ESCRT function. The architecture of the activated and membrane-bound Snf7 polymer provides crucial insights into the spatially unique ESCRT-III-mediated membrane remodeling. PMID- 26670544 TI - Lateral orbitofrontal neurons acquire responses to upshifted, downshifted, or blocked cues during unblocking. AB - The lateral orbitofrontal cortex (lOFC) has been described as signaling either outcome expectancies or value. Previously, we used unblocking to show that lOFC neurons respond to a predictive cue signaling a 'valueless' change in outcome features (McDannald, 2014). However, many lOFC neurons also fired to a cue that simply signaled more reward. Here, we recorded lOFC neurons in a variant of this task in which rats learned about cues that signaled either more (upshift), less (downshift) or the same (blocked) amount of reward. We found that neurons acquired responses specifically to one of the three cues and did not fire to the other two. These results show that, at least early in learning, lOFC neurons fire to valued cues in a way that is more consistent with signaling of the predicted outcome's features than with signaling of a general, abstract or cached value that is independent of the outcome. PMID- 26670545 TI - Plasmon resonance and the imaging of metal-impregnated neurons with the laser scanning confocal microscope. AB - The staining of neurons with silver began in the 1800s, but until now the great resolving power of the laser scanning confocal microscope has not been utilized to capture the in-focus and three-dimensional cytoarchitecture of metal impregnated cells. Here, we demonstrate how spectral confocal microscopy, typically reserved for fluorescent imaging, can be used to visualize metal labeled tissues. This imaging does not involve the reflectance of metal particles, but rather the excitation of silver (or gold) nanoparticles and their putative surface plasmon resonance. To induce such resonance, silver or gold particles were excited with visible-wavelength laser lines (561 or 640 nm), and the maximal emission signal was collected at a shorter wavelength (i.e., higher energy state). Because the surface plasmon resonances of noble metal nanoparticles offer a superior optical signal and do not photobleach, our novel protocol holds enormous promise of a rebirth and further development of silver- and gold-based cell labeling protocols. PMID- 26670546 TI - A serial multiplex immunogold labeling method for identifying peptidergic neurons in connectomes. AB - Electron microscopy-based connectomics aims to comprehensively map synaptic connections in neural tissue. However, current approaches are limited in their capacity to directly assign molecular identities to neurons. Here, we use serial multiplex immunogold labeling (siGOLD) and serial-section transmission electron microscopy (ssTEM) to identify multiple peptidergic neurons in a connectome. The high immunogenicity of neuropeptides and their broad distribution along axons, allowed us to identify distinct neurons by immunolabeling small subsets of sections within larger series. We demonstrate the scalability of siGOLD by using 11 neuropeptide antibodies on a full-body larval ssTEM dataset of the annelid Platynereis. We also reconstruct a peptidergic circuitry comprising the sensory nuchal organs, found by siGOLD to express pigment-dispersing factor, a circadian neuropeptide. Our approach enables the direct overlaying of chemical neuromodulatory maps onto synaptic connectomic maps in the study of nervous systems. PMID- 26670547 TI - Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect. AB - Aneuploidy in human eggs is the leading cause of pregnancy loss and Down's syndrome. Aneuploid eggs result from chromosome segregation errors when an egg develops from a progenitor cell, called an oocyte. The mechanisms that lead to an increase in aneuploidy with advanced maternal age are largely unclear. Here, we show that many sister kinetochores in human oocytes are separated and do not behave as a single functional unit during the first meiotic division. Having separated sister kinetochores allowed bivalents to rotate by 90 degrees on the spindle and increased the risk of merotelic kinetochore-microtubule attachments. Advanced maternal age led to an increase in sister kinetochore separation, rotated bivalents and merotelic attachments. Chromosome arm cohesion was weakened, and the fraction of bivalents that precociously dissociated into univalents was increased. Together, our data reveal multiple age-related changes in chromosome architecture that could explain why oocyte aneuploidy increases with advanced maternal age. PMID- 26670548 TI - Central kynurenine pathway shift with age in women. AB - Age is considered a dominant risk factor in the development of most neurodegenerative disorders. The kynurenine pathway, a major metabolic pathway of tryptophan is altered in the majority of neurodegenerative disorders. In this study, we have analysed CSF samples from 49 healthy women across a wide age range (0-90) for kynurenine pathway metabolites and the inflammatory marker neopterin. Our results show central tryptophan metabolism is increased with age in women, with an apparent shift towards the neurotoxin quinolinic acid. We also observed an increase in central levels of the inflammatory marker neopterin with age and a positive correlation between neopterin and kynurenine pathway activation. We conclude that, the changes that occur in the kynurenine pathway as a result of normal ageing are mechanistically linked to increased inflammatory signalling and have some explanatory potential with regard to age-associated degenerative diseases in the CNS. Management of health in ageing and (preventative) treatment would do well to look to the kynurenine pathway for potentially novel solutions. Both the inflammation marker neopterin and kynurenine pathway activity were increased with age in the CSF of female subjects. While levels of quinolinic acid (QUIN), picolinic acid (PIC), kynurenine and quinaldic acid (QA) were increased, 3-hydroxykynurenine (3HK) was decreased and 3-hydroxyanthranilic acid (3HAA) and kynurenic acid (KYNA) remained unchanged. Of particular interest is the increase in QUIN, a neuroexcitotoxin associated with neurodegeneration. PMID- 26670549 TI - Team Process Variation Across Diabetes Quality of Care Trajectories. AB - Conceptual frameworks in health care do not address mechanisms whereby teamwork processes affect quality of care. We seek to fill this gap by applying a framework of teamwork processes to compare different patterns of primary care performance over time. We thematically analyzed 114 primary care staff interviews across 17 primary care clinics. We purposefully selected clinics using diabetes quality of care over 3 years using four categories: consistently high, improving, worsening, and consistently low. Analyses compared participant responses within and between performance categories. Differences were observed among performance categories for action processes (monitoring progress and coordination), transition processes (goal specification and strategy formulation), and interpersonal processes (conflict management and affect management). Analyses also revealed emergent concepts related to psychological and organizational context that were reported to affect team processes. This study is a first step toward a comprehensive model of how teamwork processes might affect quality of care. PMID- 26670550 TI - Changes in Public Prenatal Care Coverage Options for Noncitizens Since Welfare Reform: Wide State Variation Remains. AB - Before 1996, most lawfully present noncitizens were eligible for the same prenatal Medicaid benefits as U.S. citizens. However, the 1996 Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA)-welfare reform restricted benefits for certain lawful noncitizens for the first time. Welfare reform also gave states unprecedented authority to determine Medicaid eligibility. More recent federal policy changes have allowed states to cover some noncitizen pregnant women initially excluded under welfare reform. However, there are few comprehensive studies examining state implementation of these policy options. This study documents state-level trends in prenatal Medicaid and state funded coverage options for low-income noncitizens just prior to and since welfare reform. While some states have substantially expanded prenatal coverage since PRWORA, wide variation remains. These findings have important implications for understanding the potential effects of the Affordable Care Act and Medicaid expansion on health care utilization and birth outcomes among pregnant noncitizens. PMID- 26670551 TI - Atomic Scale Plasmonic Switch. AB - The atom sets an ultimate scaling limit to Moore's law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocation of an individual or, at most, a few atoms in a plasmonic cavity. Depending on the location of the atom either of two distinct plasmonic cavity resonance states are supported. Experimental results show reversible digital optical switching with an extinction ratio of 9.2 dB and operation at room temperature up to MHz with femtojoule (fJ) power consumption for a single switch operation. This demonstration of an integrated quantum device allowing to control photons at the atomic level opens intriguing perspectives for a fully integrated and highly scalable chip platform, a platform where optics, electronics, and memory may be controlled at the single-atom level. PMID- 26670552 TI - Antiviral drugs for seasonal influenza 2015-2016. PMID- 26670553 TI - Intravenous diclofenac (Dyloject). PMID- 26670554 TI - Empagliflozin/metformin (Synjardy) for type 2 diabetes. PMID- 26670555 TI - In brief: oral phenylephrine for nasal congestion. PMID- 26670556 TI - Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis. AB - BACKGROUND: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. OBJECTIVE: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. METHODS: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). RESULTS: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. CONCLUSIONS: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed. PMID- 26670557 TI - Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. AB - The farnesoid X receptor (FXR) regulates bile acid, lipid and glucose metabolism. Here we show that treatment of mice with glycine-beta-muricholic acid (Gly-MCA) inhibits FXR signalling exclusively in intestine, and improves metabolic parameters in mouse models of obesity. Gly-MCA is a selective high-affinity FXR inhibitor that can be administered orally and prevents, or reverses, high-fat diet-induced and genetic obesity, insulin resistance and hepatic steatosis in mice. The high-affinity FXR agonist GW4064 blocks Gly-MCA action in the gut, and intestine-specific Fxr-null mice are unresponsive to the beneficial effects of Gly-MCA. Mechanistically, the metabolic improvements with Gly-MCA depend on reduced biosynthesis of intestinal-derived ceramides, which directly compromise beige fat thermogenic function. Consequently, ceramide treatment reverses the action of Gly-MCA in high-fat diet-induced obese mice. We further show that FXR signalling in ileum biopsies of humans positively correlates with body mass index. These data suggest that Gly-MCA may be a candidate for the treatment of metabolic disorders. PMID- 26670558 TI - Folic acid supplementation, preconception body mass index, and preterm delivery: findings from the preconception cohort data in a Chinese rural population. AB - BACKGROUND: Folic acid (FA) supplementation before and during the first trimester can reduce the risk of occurrence of preterm delivery (PTD). Preconception body mass index (BMI) is also associated with PTD. This study aimed to investigate the combined effect of FA supplements and preconception BMI on the risk of PTD. METHODS: The data of a cohort from 2010-2011 that was obtained through a preconception care service in China was used (including 172,206 women). A multivariable regression model was used to investigate the association between maternal preconception conditions and the risk of PTD. The interaction of preconception BMI and FA supplementation was measured by a logistic regression model. RESULTS: Taking FA supplements in the preconception period or in the first trimester reduced the risk of PTD (odds ratio [OR] = 0.58 and OR = 0.61, respectively). Women with an abnormal BMI had an increased risk of PTD (OR = 1.09, OR = 1.10, and OR = 1.17 for underweight, overweight, and obese, respectively). Preconception BMI showed an interaction with the protective effect of FA supplementation for PTD. With regard to the interaction of FA supplementation, the adjusted odds ratio (aOR) was 0.57 (95% CI: 0.51, 0.64) in underweight women, 0.85 (95% CI: 0.73, 0.98) in overweight women, and 0.77 (95% CI, 0.65, 0.91) in obese women. Preconception BMI also showed an interaction with the time of FA supplementation. Women with a normal BMI who began to take FA supplements in the preconception period had the lowest risk of PTD (aORs: 0.58 vs. 0.65 beginning in the first trimester). The aORs at preconception and the first trimester in the underweight group were 0.56 vs. 0.60. The aORs at preconception and the first trimester were 0.94 vs. 0.65 and 1.15 vs. 0.60 in the overweight and obesity groups, respectively. CONCLUSIONS: In our study, FA supplements reduced the risk of PTD, while abnormal BMI raised the risk of PTD, although higher BMI categories did not have this higher risk once adjusted analysis was conducted. The protective effect of FA supplementation for PTD was reduced in women with overweight or obesity. To get better protection of FA supplementation, women with normal BMI or underweight should begin to use in preconception, while women with overweight or obesity should begin to use after conception. PMID- 26670560 TI - A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens. AB - Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID- 26670561 TI - Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy. AB - Penile squamous cell carcinoma (PeSCCA) is a rare malignancy for which there are limited treatment options due to a poor understanding of the molecular alterations underlying disease development and progression. Therefore, we performed comprehensive, targeted next-generation sequencing to identify relevant somatic genomic alterations in a retrospective cohort of 60 fixed tumor samples from 43 PeSCCA cases (including 14 matched primary/metastasis pairs). We identified a median of two relevant somatic mutations and one high-level copy number alteration per sample (range, 0-5 and 0-6, respectively). Expression of HPV and p16 was detectable in 12% and 28% of patients, respectively. Furthermore, advanced clinical stage, lack of p16 expression, and MYC and CCND1 amplifications were significantly associated with shorter time to progression or PeSCCA-specific survival. Notably, four cases harbored EGFR amplifications and one demonstrated CDK4 amplification, genes for which approved and investigational targeted therapies are available. Importantly, although paired primary tumors and lymph node metastases were largely homogeneous for relevant somatic mutations, we identified heterogeneous EGFR amplification in primary tumor/lymph node metastases in 4 of 14 cases, despite uniform EGFR protein overexpression. Likewise, activating HRAS mutations occurred in 8 of 43 cases. Taken together, we provide the first comprehensive molecular PeSCCA analysis, which offers new insight into potential precision medicine approaches for this disease, including strategies targeting EGFR. PMID- 26670563 TI - Correction: Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation. PMID- 26670562 TI - Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small Molecule Inhibitors. AB - Mesenchymal-epithelial transition (MET) blockade offers a new targeted therapy particularly in those cancers with MET amplification. However, the efficacy and the duration of the response to MET inhibitors are limited by the emergence of drug resistance. Here, we report that resistance to small-molecule inhibitors of MET can arise from increased expression of the prosurvival Pim protein kinases. This resistance mechanism was documented in non-small cell lung cancer and gastric cancer cells with MET amplification. Inhibition of Pim kinases enhanced cell death triggered by short-term treatment with MET inhibitors. Pim kinases control the translation of antiapoptotic protein Bcl-2 at an internal ribosome entry site and this mechanism was identified as the basis for Pim-mediated resistance to MET inhibitors. Protein synthesis was increased in drug-resistant cells, secondary to a Pim-mediated increase in cap-independent translation. In cells rendered drug resistant by chronic treatment with MET inhibitors, genetic or pharmacologic inhibition of Pim kinases was sufficient to restore sensitivity in vitro and in vivo. Taken together, our results rationalize Pim inhibition as a strategy to augment responses and blunt acquired resistance to MET inhibitors in cancer. PMID- 26670564 TI - Clinical Outcomes of Remote Peritoneal Dialysis Patients: A Retrospective Cohort Study from a Single Center in China. AB - BACKGROUND/AIMS: To investigate clinical outcomes of remote peritoneal dialysis (PD) patients in Southern China. METHODS: In this retrospective cohort study, incident remote PD patients managed with a comprehensive follow-up program in our PD center were included and clinical outcomes were estimated. RESULTS: One thousand and five remote PD patients with mean age 46.1 +/- 14.6 years, of which 38.1% were women, were followed-up for a median of 35.7 months. Patient survival rates were 95.4, 84.7 and 71.8% and death-censored technique survival rates were 98.6, 92.3 and 83.4% at 1, 3 and 5 years, respectively. Peritonitis rate was 0.16 episodes per patient-year. Advanced age, diabetes mellitus, shorter peritonitis free survival time, poor compliance for regular visiting nephrologists and lower hemoglobin predicted all-cause mortality of remote PD patients. CONCLUSION: The remote PD patients in Southern China managed with comprehensive follow-up program had favorable clinical outcomes, which indicated that home-based PD therapy could be an appropriate treatment option for remote end-stage kidney disease patients. PMID- 26670566 TI - Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties. AB - Glioblastoma is one of the most malignant brain tumors with poor prognosis and their development and progression are known to be driven by glioblastoma stem cells. Although glioblastoma stem cells lose their cancer stem cell properties during cultivation in serum-containing medium, little is known about the molecular mechanisms regulating signaling alteration in relation to reduction of stem cell-like characteristics. To elucidate the global phosphorylation-related signaling events, we performed a SILAC-based quantitative phosphoproteome analysis of serum-induced dynamics in glioblastoma stem cells established from the tumor tissues of the patient. Among a total of 2876 phosphorylation sites on 1584 proteins identified in our analysis, 732 phosphorylation sites on 419 proteins were regulated through the alteration of stem cell-like characteristics. The integrative computational analyses based on the quantified phosphoproteome data revealed the relevant changes of phosphorylation levels regarding the proteins associated with cytoskeleton reorganization such as Rho family GTPase and Intermediate filament signaling, in addition to transforming growth factor beta receptor type-2 (TGFBR2) as a prominent upstream regulator involved in the serum-induced phosphoproteome regulation. The functional association of transforming growth factor-beta receptor type-2 with stem cell-like properties was experimentally validated through signaling perturbation using the corresponding inhibitors, which indicated that transforming growth factor-beta receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. PMID- 26670572 TI - Urogynecology digest : Presented by Kim van Delft. PMID- 26670565 TI - Proteogenomics from a bioinformatics angle: A growing field. AB - Proteogenomics is a research area that combines areas as proteomics and genomics in a multi-omics setup using both mass spectrometry and high-throughput sequencing technologies. Currently, the main goals of the field are to aid genome annotation or to unravel the proteome complexity. Mass spectrometry based identifications of matching or homologues peptides can further refine gene models. Also, the identification of novel proteoforms is also made possible based on detection of novel translation initiation sites (cognate or near-cognate), novel transcript isoforms, sequence variation or novel (small) open reading frames in intergenic or un-translated genic regions by analyzing high-throughput sequencing data from RNAseq or ribosome profiling experiments. Other proteogenomics studies using a combination of proteomics and genomics techniques focus on antibody sequencing, the identification of immunogenic peptides or venom peptides. Over the years, a growing amount of bioinformatics tools and databases became available to help streamlining these cross-omics studies. Some of these solutions only help in specific steps of the proteogenomics studies, e.g. building custom sequence databases (based on next generation sequencing output) for mass spectrometry fragmentation spectrum matching. Over the last few years a handful integrative tools also became available that can execute complete proteogenomics analyses. Some of these are presented as stand-alone solutions, whereas others are implemented in a web-based framework such as Galaxy. In this review we aimed at sketching a comprehensive overview of all the bioinformatics solutions that are available for this growing research area. (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:584-599, 2017. PMID- 26670567 TI - Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine. AB - INTRODUCTION: Periodontitis is one of the most widespread infectious diseases in humans. We previously promoted significant periodontal tissue regeneration in swine models with the transplantation of autologous periodontal ligament stem cells (PDLSCs) and PDLSC sheet. We also promoted periodontal tissue regeneration in a rat model with a local injection of allogeneic bone marrow mesenchymal stem cells. The purpose of the present study is to investigate the roles of the hepatocyte growth factor (HGF) and human dental pulp stem cells (DPSCs) in periodontal tissue regeneration in swine. METHOD: In the present study, we transferred an adenovirus that carried HGF gene into human DPSCs (HGF-hDPSCs) under good manufacturing practice (GMP) conditions. These cells were then transplanted into a swine model for periodontal regeneration. Twenty miniature pigs were used to generate periodontitis with bone defect of 5 mm in width, 7 mm in length, and 3 mm in depth. After 12 weeks, clinical, radiological, quantitative and histological assessment of regenerated periodontal tissues was performed to compare periodontal regeneration in swine treated with cell implantation. RESULTS: Our study showed that injecting HGF-hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. A hDPSC or HGF-hDPSC sheet showed superior periodontal tissue regeneration compared to the injection of dissociated cells. However, the sheets required surgical placement; thus, they were suitable for surgically-managed periodontitis treatments. The adenovirus-mediated transfer of the HGF gene markedly decreased hDPSC apoptosis in a hypoxic environment or in serum-free medium, and it increased blood vessel regeneration. CONCLUSION: This study indicated that HGF-hDPSCs produced under GMP conditions significantly improved periodontal bone regeneration in swine; thus, this method represents a potential clinical application for periodontal regeneration. PMID- 26670573 TI - Epidemiology of mixed, stress, and urgency urinary incontinence in middle aged/older women: the importance of incontinence history. AB - INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is common and the relationship among its subtypes complex. Our objective was to describe the natural history and predictors of the incontinence subtypes stress, urgency, and mixed, in middle-aged and older US women. We tested our hypothesis that UI subtype history predicted future occurrence, evaluating subtype incidence/remission over multiple time points in a stable cohort of women. METHODS: We analyzed longitudinal urinary incontinence data in 10,572 community dwelling women aged >=50 in the 2004-2010 Health and Retirement Study. Mixed, stress, and urgency incontinence prevalence (2004, 2006, 2008, 2010) and 2-year cumulative incidence and remissions (2004-2006, 2006-2008, 2008-2010) were estimated. Patient characteristics and incontinence subtype status 2004-2008 were entered into a multivariable, transition model to determine predictors for incontinence subtype occurrence in 2010. RESULTS: The prevalence of each subtype in this population (median age 63-66) was 2.6-8.9 %. Subtype incidence equaled 2.1-3.5 % and remissions for each varied between 22.3 and 48.7 %. Incontinence subtype incidence predictors included ethnicity/race, age, body mass index, and functional limitations. Compared with white women, black women had decreased odds of incident stress incontinence and Hispanic women had increased odds of stress incontinence remission. The age range 80-90 and severe obesity predicted incident mixed incontinence. Functional limitations predicted mixed and urgency incontinence. The strongest predictor of incontinence subtype was subtype history. The presence of the respective incontinence subtypes in 2004 and 2006 strongly predicted 2010 recurrence (odds ratio [OR] stress incontinence = 30.7, urgency OR = 47.4, mixed OR = 42.1). CONCLUSIONS: Although the number of remissions was high, a previous history of incontinence subtypes predicted recurrence. Incontinence status is dynamic, but tends to recur over the longer term. PMID- 26670574 TI - Long-term outcomes after the excision of horseshoe urethral diverticulum. AB - INTRODUCTION AND HYPOTHESIS: The objective was to report our long-term experience with horseshoe urethral diverticulum (HUD) excised using the urethral preservation technique. METHODS: Following IRB approval, charts of women who underwent HUD excision and had at least 6 months' follow-up were reviewed. HUD was defined as a bilateral posterior diverticulum that extended laterally and anteriorly past 3 and 9 o'clock on the left and right sides respectively. HUD was diagnosed by pre-operative MRI. Success was defined as no evidence of residual diverticulum on post-operative imaging and the reported resolution of diverticulum symptoms. RESULTS: Between 1998 and 2014, 12 out of 15 women who underwent HUD excision met the inclusion criteria. Mean follow-up was 81 (median: 52, range: 7-163) months. Presenting symptoms included urinary leakage (n = 8), dyspareunia (n = 6), dysuria (n = 6), frequency (n = 5), urgency (n = 5), and vaginal pain (n = 8). Two patients reported having all three symptoms of the historic triad: dysuria, dyspareunia, and post-void dribbling. Three patients had prior urological interventions, including excision of a unilateral diverticulum, a Spence procedure, and a Skene gland incision. Only 1 patient had a recurrent HUD confirmed by MRI 10 years later, which required reoperation. HUD symptoms resolved in the remaining 11 patients, with post-operative imaging showing no evidence of recurrent HUD, and no further therapy was needed. Of 4 women who reported stress urinary incontinence (SUI) pre-operatively, only 2 reported SUI symptoms post-operatively. There were no cases of post-operative urethro-vaginal fistula. CONCLUSION: At a mean follow-up of 6-7 years, excision of HUD with urethral preservation produced long-lasting resolution in the majority of patients. PMID- 26670575 TI - Transobturator tape versus retropubic tension-free vaginal tape for stress urinary incontinence: 5-year safety and effectiveness outcomes following a randomised trial. AB - INTRODUCTION AND HYPOTHESIS: In a randomised trial comparing transobturator tape (TOT) to retropubic tension-free vaginal tape (TVT) for women with stress urinary incontinence (SUI), vaginal examination at 12 months showed that tapes were palpable for 80.0 % of the TOT group versus 26.7 % of the TVT group. We hypothesized that this difference would lead to more women in the TOT group experiencing vaginal mesh erosion or other serious adverse events compared to women in the TVT group 5 years after surgery. METHODS: All participants were invited to join the follow-up study after being randomised to receive TOT or TVT for SUI. Consenting women had a vaginal examination, a pad test for urinary incontinence (UI) and completed Health-related Quality of Life Questionnaires (HRQOL). Women unable to attend the clinic completed questionnaires only. The primary composite outcome incorporated mesh exposure, urinary retention, repeat incontinence surgery and moderate to severe pelvic pain. Assuming 80 % follow-up, our study would have 67 % power to detect a difference in primary outcome (two sided 5 % level of significance). Comparisons between groups used chi-square tests and t tests. RESULTS: One hundred and seventy-six (88.4 %) women participated in the 5-year follow-up (83 TOT, 93 TVT). The primary composite outcome occurred in 21.8 % of the TOT and 27.6 % of the TVT groups [difference = 5.8 %, 95 % confidence interval (CI) -18.9 % to 7.3 %, p value 0.39)] Vaginal examination found more women with palpable tapes in the TOT versus the TVT group (48.5 % versus 22.4 %, p value 0.001). There were no other significant differences between groups. CONCLUSIONS: Serious adverse events and tape effectiveness did not differ between groups at 5 years. Palpable tape remains a concern for women who receive TOT for treating SUI. PMID- 26670576 TI - A randomised comparison of single-incision versus traditional transobturator midurethral sling in women with stress urinary incontinence: results of a 24 month follow-up. AB - INTRODUCTION AND HYPOTHESIS: Midurethral sling procedures have become the principal surgical treatment for women with stress urinary incontinence (SUI). The 1-year results of this international trial comparing the efficacy and morbidity of a single-incision midurethral sling (SIMS; MiniArc) and a transobturator standard midurethral sling (SMUS; Monarc) showed that MiniArc is non-inferior regarding subjective cure and superior with regard to postoperative pain and recovery. The objective was to compare subjective and objective cure, morbidity and surgery-related discomfort following SIMS and transobturator SMUS up to a 24-month follow-up. METHODS: We carried out a non-blinded, randomised, controlled trial. Women with symptomatic SUI were eligible. Primary outcome was subjective cure, defined as an improvement on the Patient Global Impression of Improvement (PGI-I), at 12, 24 and 36 months. Secondary outcomes were objective cure based on the cough stress test, disease-specific quality of life questionnaires, surgical parameters and physical performance during recovery. Analysis was by intent to treat. Differences between the two groups regarding dichotomous variables were Chi-squared tested and presented as relative risks (RR) with corresponding 95 % confidence intervals. RESULTS: We randomised 97 women to MiniArc and 96 to Monarc. At the 24-month follow-up, subjective cure was 84 % following MiniArc and 89 % following Monarc (RR -5; 95% CI -0.17 to 0.06). Objective cure was 93 % following MiniArc and 94 % following Monarc (RR -1; 95% CI -0.10 to 0.07). Both procedures have low complication rates. CONCLUSIONS: At the 2-year follow-up, the non-prespecified analysis of this randomised trial showed that the MiniArc, a single-incision sling, had similar subjective and similar objective cure rates, although non-inferiority to Monarc for subjective cure could not be demonstrated. PMID- 26670577 TI - The prevalence of abnormal posterior compartment anatomy and its association with obstructed defecation symptoms in urogynecological patients. AB - INTRODUCTION AND HYPOTHESIS: Symptoms of obstructive defecation (OD) are common in women. Transperineal ultrasound (TPUS) has been used for the evaluation of defecatory disorders. The aim of our study was to determine the overall prevalence of anatomical abnormalities of the posterior compartment and their correlations with OD in women seen in a tertiary urogynecology clinic. METHODS: This is a retrospective study on 750 women seen at a tertiary urogynecological unit who had undergone a standardized interview, clinical examination, and 4D TPUS. Univariate and multivariate logistic regression analyses were undertaken to study the association between examination findings and symptoms of OD. This study was approved by the local human research ethics committee (Nepean Blue Mountains Local Health District Human Research Ethics Committee, IRB approval no. 13-16). RESULTS: The datasets of 719 women were analyzed. Mean age was 56.1 (18.4-87.6) years. Ninety-seven patients (13 %) reported fecal incontinence, 190 (26 %) constipation, and 461 (64 %) symptoms of OD. On examination, 405 women (56 %) were diagnosed with significant posterior compartment prolapse (POP-Q >= stage 2), which was associated with symptoms of OD (p < 0.0001). On ultrasound, 103 (14 %) patients had an enterocele, 382 (53 %) a true rectocele and 31 (4.3 %) had rectal intussusception. On multivariate analysis true rectocele (p = 0.003) and rectal intussusception (p = 0.004) remained significantly associated with symptoms of OD. CONCLUSION: Both symptoms of OD and anatomical abnormalities of the posterior compartment are highly prevalent in urogynecological patients. Ultrasound findings of a true rectocele and rectal intussusception are significantly associated with obstructed defecation. PMID- 26670578 TI - Skene's gland cyst excision. AB - INTRODUCTION AND HYPOTHESIS: We review our experience with long-term outcome after Skene's gland cyst excision. MATERIALS AND METHODS: After receiving institutional review board approval, we reviewed a surgical database of all procedures performed by two surgeons at one institution for Skene's gland cyst excision. Parameters evaluated include presenting symptoms, preoperative evaluation, excision site, perioperative complications, and clinical outcomes. The technique of surgical excision is presented in the accompanying video, and includes cystoscopy, dissection of cyst wall from the floor of the urethra, complete removal of the cyst wall, and primary vaginal-wall closure. RESULTS: From 2001 to 2013, ten women underwent Skene's gland cyst excision. Mean follow up was 3.5 years (range 3-96 months). Presenting symptoms were dyspareunia (4), urinary tract infections (4), vaginal mass (1), and voiding dysfunction (1). Five patients had more than one presenting symptom. To exclude urethral diverticulum, magnetic resonance imaging (MRI) was done in all patients and a voiding cystourethrogram in five. No perioperative complications were reported. A distal meatoplasty was done in two women. No recurrence occurred. Eight of ten women who were sexually active remained sexually active postoperatively. CONCLUSIONS: Excision of Skene's gland cyst is a safe procedure with acceptable long-term functional outcomes. PMID- 26670579 TI - Mechanistic studies of pyridinium electrochemistry: alternative chemical pathways in the presence of CO2. AB - Protonated heterocyclic amines, such as pyridinium, have been utilized as catalysts in the electrocatalytic reduction of carbon dioxide. While these represent a new and exciting class of electrocatalysts, the details of the mechanism and faradaic processes occurring in solution are unclear. We report a series of cyclic voltammetry experiments involving Pt, Ag, Au, and Cu electrodes, under both aqueous and nonaqueous conditions, directed towards gaining an improved mechanistic understanding of pyridinium electrochemistry. Surface enhanced Raman (SER) spectroelectrochemistry was also performed on Cu film-over nanosphere electrodes in order to identify adsorbed species. It was found that the reduction potential of pyridinium (-0.58 V vs. SCE) and its electrochemical reversibility are unique features of platinum electrodes. In contrast, the reduction potentials on Ag, Au, and Cu electrodes are ~400 mV more negative than Pt in both the presence and the absence of CO2. SER spectroelectrochemistry of pyridinium solutions shows no evidence for a pyridinium radical or a pyridinium ion. Increased cathodic current in the presence of CO2 is only detected at scan rates less than 10 mV s(-1) in aqueous solutions. The addition of CO2 resulted in a shift in the potential for the hydrogen evolution reaction. Pyridinium electrochemistry was observed under nonaqueous conditions; however no increase in cathodic current was observed when CO2 was added to the solution. Based on this set of results it is concluded that the reduction potential of pyridinium is surface dependent, CO2 acts as a pseudo-reserve of H(+), and pyridinium and CO2 create an alternative mechanism for hydrogen evolution. PMID- 26670580 TI - Siamese-Twin Porphyrin Origami: Oxidative Fusing and Folding. AB - Oxidation of a nonaromatic Siamese-twin porphyrin, a pyrazole-containing expanded porphyrin with two porphyrinlike binding pockets, with a stoichiometric amount of the two-electron, two-proton oxidizing agent 2,3-dichloro-5,6-dicyano-1,4 benzochinone led to the formation of a single N(pz) -C(o-Ph) linkage between the pyrazole unit with a neighboring meso-phenyl group, forming a pyrazolo- [1,5 a]indole moiety. Repeated treatment with a second equivalent of the oxidant yielded a doubly N-fused species, involving the second pyrazole moiety. The conversion products were characterized by variable-temperature and multinuclear 1D and 2D NMR spectroscopy. The fusions strongly alter the conformation of the macrocycles, as shown by X-ray diffraction analyses of all three compounds, eventually leading to a folded structure. UV/Vis and NMR-spectroscopic investigations indicated the presence of highly delocalized but nonmacrocycle aromatic pi systems. This behavior of the Siamese-twin porphyrin in response to oxidation is in contrast to the behavior of related all-pyrrole-based expanded macrocycles that switch, by redox processes and protonation, between Huckel and Mobius aromatic states. PMID- 26670581 TI - Decoupling the Direct and Indirect Biological Effects of ZnO Nanoparticles Using a Communicative Dual Cell-Type Tissue Construct. AB - While matter at the nanoscale can be manipulated, the knowledge of the interactions between these nanoproducts and the biological systems remained relatively laggard. Current nanobiology study is rooted on in vitro study using conventional 2D cell culture model. A typical study employs monolayer cell culture that simplifies the real context of which to measure any nanomaterial effect; unfortunately, this simplification also demonstrated the limitations of 2D cell culture in predicting the actual biological response of some tissues. In fact, some of the characteristics of tissue such as spatial arrangement of cells and cell-cell interaction, which are simplified in 2D cell culture model, play important roles in how cells respond to a stimulus. To more accurately recapitulate the features and microenvironment of tissue for nanotoxicity assessments, an improved organotypic-like in vitro multicell culture system to mimic the kidney endoepithelial bilayer is introduced. Results showed that important nano-related parameters such as the diffusion, direct and indirect toxic effects of ZnO nanoparticles can be studied by combining this endoepithelial bilayer tissue model and traditional monolayer culture setting. PMID- 26670582 TI - Wetting behaviour and contact angles anisotropy of nematic nanodroplets on flat surfaces. AB - We have studied the wetting behaviour of liquid crystal nanodroplets deposited on a planar surface, modelling the mesogens with Gay-Berne ellipsoids and the support surface with a slab of Lennard-Jones (LJ) spherical particles whose mesogen-surface affinity can be tuned. A crystalline and an amorphous planar surface, both showing planar anchoring, have been investigated: the first is the (001) facet of a LJ fcc crystal, the second is obtained from a disordered LJ glass. In both cases we find that the deposited nanodroplet is, in general, elongated and that the contact angle changes around its contour. Simulations for the crystalline substrate show that the angle of contact turns reversibly from anisotropic to isotropic when crossing the clearing transition. As far as we know this is a novel, not yet explored effect for thermotropic liquid crystals, that we hope will stimulate experimental investigations. PMID- 26670583 TI - Quantitative MRI water content mapping of porcine intervertebral disc during uniaxial compression. AB - BACKGROUND: Intervertebral disc (IVD) diseases are major public health problem in industrialized countries where they affect a large proportion of the population. In particular, IVD degeneration is considered to be one of the leading causes of pain consultation and sick leave. The aim of this study was to develop a new method for assessing the functionality of IVD in order to diagnose IVD degeneration. METHODS: For this purpose, we have designed a specific device that enables to mechanically load porcine IVD ex vivo in the 4.7-Tesla horizontal superconducting magnet of a magnetic resonance (MR) scanner. Proton density weighted imaging (rhoH-MRI) of the samples was acquired. FINDINGS: The post processing on MR images allowed (1) to reconstruct the 3D deformation under a known mechanical load and (2) to infer the IVD porosity assuming an incompressible poroelastic model. INTERPRETATION: This study demonstrates the ability to follow the change in morphology and hydration of an IVD using MR measurements, thereby providing valued information for a better understanding of IVD function. PMID- 26670584 TI - Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells. AB - Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcgamma receptor mediated cell cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64(+) monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients' inflamed joints that comprised enhanced numbers of CD64(+) cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64(+) cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64(+) cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcgammaR, but also the immunological environment that is appropriate to support such interactions. PMID- 26670585 TI - Polyglucosan bodies in intramuscular nerve branches are a poor predictor of GBE1 mutation and adult polyglucosan body disease. AB - INTRODUCTION: Adult polyglucosan body disease (APBD) is associated with formation of polyglucosan bodies in peripheral nerve branches. Some muscle biopsies show these inclusions in intramuscular nerve branches. It has not been established whether the presence of multiple polyglucosan bodies in intramuscular peripheral nerve branches could or should suggest testing for APBD. METHODS: Fifteen muscle biopsies from adults between the ages of 36 and 84 years, all showing polyglucosan bodies in intramuscular peripheral nerve twigs, were tested by sequencing of the GBE1 gene. RESULTS: In 4 patients, testing identified heterozygous missense mutations not previously described. No homozygous or compound heterozygous mutations were identified. CONCLUSIONS: The presence of polyglucosan bodies in intramuscular nerve twigs by itself, even if they are multiple, is not an indication of APBD. Further testing may only be indicated in patients with clinical disease manifestations. PMID- 26670586 TI - Parsing Based on Parselets: A Unified Deformable Mixture Model for Human Parsing. AB - Human parsing, namely partitioning the human body into semantic regions, has drawn much attention recently for its wide applications in human-centric analysis. Previous works often consider solving the problem of human pose estimation as the prerequisite of human parsing. We argue that these approaches cannot obtain optimal pixel-level parsing due to the inconsistent targets between the different tasks. In this work, we directly address the problem of human parsing by using the novel Parselet representation as the building blocks of our parsing model. Parselets are a group of parsable segments which can generally be obtained by low-level over-segmentation algorithms and bear strong semantic meaning. We then build a deformable mixture parsing model (DMPM) for human parsing to simultaneously handle the deformation and multi-modalities of Parselets. The proposed model has two unique characteristics: (1) the possible numerous modalities of Parselet ensembles are exhibited as the "And-Or" structure of sub-trees; (2) to further solve the practical problem of Parselet occlusion or absence, we directly model the visibility property at some leaf nodes. The DMPM thus directly solves the problem of human parsing by searching for the best graph configuration from a pool of Parselet hypotheses without intermediate tasks. Fast rejection based on hierarchical filtering is employed to ensure the overall efficiency. Comprehensive evaluations on a new large-scale human parsing dataset, which is crawled from the Internet, with high resolution and thoroughly annotated semantic labels at pixel-level, and also a benchmark dataset demonstrate the encouraging performance of the proposed approach. PMID- 26670588 TI - Synthesis of an N-Heterocyclic-Carbene-Stabilized Siladiimide. AB - The reaction of the N-heterocyclic-carbene-stabilized disilicon(0) complex [IPr >Si?Si<-IPr] (1; IPr = :C{N(Ar)CH}2 and Ar = 2,6-iPr2C6H3) with ArN3 afforded the N-heterocyclic-carbene-stabilized siladiimide [ArNSi(IPr)NAr] (2). X-ray crystallography and theoretical studies show that the N-Si-N skeleton in compound 2 possesses considerable double-bond character and the Si atom is stabilized by the N-heterocyclic carbene. PMID- 26670587 TI - Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer. AB - BACKGROUND: Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. MATERIALS AND METHODS: From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m(2) and Cetuximab were given weekly during radiation therapy. RESULTS: Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3-4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3-4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. CONCLUSIONS: The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients' selection is crucial in order to treat patients appropriately. PMID- 26670589 TI - Changes in morphology of retinal ganglion cells with eccentricity in retinal degeneration. AB - Ganglion cells are the output neurons of the retina and are known to remodel during the subtle plasticity changes that occur following the death of photoreceptors in inherited retinal degeneration. We examine the influence of retinal eccentricity on anatomical remodelling and ganglion cell morphology well after photoreceptor loss. Rd1 mice that have a mutation in the beta subunit of phosphodiesterase 6 were used as a model of retinal degeneration and gross remodelling events were examined by processing serial sections for immunocytochemistry. Retinal wholemounts from rd1-Thy1 and control Thy1 mice that contained a fluorescent protein labelling a subset of ganglion cells were processed for immunohistochemistry at 11 months of age. Ganglion cells were classified based on their soma size, dendritic field size and dendritic branching pattern and their dendritic fields were analysed for their length, area and quantity of branching points. Overall, more remodelling was found in the central compared with the peripheral retina. In addition, the size and complexity of A2, B1, C1 and D type ganglion cells located in the central region of the retina decreased. We propose that the changes in ganglion cell morphology are correlated with remodelling events in these regions and impact the function of retinal circuitry in the degenerated retina. PMID- 26670591 TI - Hepatic drug transporters: the journey so far. AB - INTRODUCTION: The key role of transporter biology in both the manifestation and treatment of disease is now firmly established. Experiences of sub-optimal drug exposure due to drug-transporter interplay have supported incorporation of studies aimed at understanding the interactions between compounds and drug transporters much earlier in drug discovery. While drug transporters can impact the most pivotal pharmacokinetic parameter with respect to human dose and exposure projections, clearance, at a renal or hepatobiliary level, the latter will form the focus of this perspective. AREAS COVERED: A synopsis of guidelines on which transporters to study together with an overview of the currently available toolkit is presented. A perspective on when to conduct studies with various hepatic transporters is also provided together with structural "alerts" which should prompt early investigation. EXPERT OPINION: Great progress has been made in individual laboratories and via consortia to understand the role of drug transporters in disease, drug disposition, drug-drug interactions and toxicity. A systematic analysis of the value posed by the available approaches and an inter lab comparison now seems warranted. The emerging ability to use physico-chemical properties to guide future screening cascades promises to revolutionise the efficiency of early drug discovery. PMID- 26670592 TI - Epilepsy case with focal cerebral herniation into the sigmoid sinus. PMID- 26670593 TI - Coronary artery calcium score and CT angiography in asymptomatic elderly patients with high pretest probability for coronary artery disease. AB - PURPOSE: To evaluate the role of coronary artery calcium scoring (CACS) and/or coronary CT angiography (CCTA) in asymptomatic elderly patients with high pretest probability for coronary artery disease (CAD). MATERIALS AND METHODS: Forty-eight consecutive asymptomatic elderly (>65 years) subjects who had a high pretest probability and underwent CACS/CCTA were included. Each CCTA was evaluated for adequacy for assessment of coronary stenosis. Significant stenosis (>50% diameter narrowing) was assessed on evaluable CT images and by invasive catheter angiography (ICA). RESULTS: All subjects were men with mean CACS of 880 +/- 1779. Among those with low (0-99), intermediate (100-399), and high (400-999) CACS, ICA verified significant stenosis was present in 8% (1/13), 23% (2/13), and 67% (8/12), respectively. Among those with very high CACS (>= 1000) (n = 10), 90% of CCTAs were not evaluable for stenosis. CONCLUSION: In asymptomatic elderly subjects with high pretest probability, CACS followed by CCTA may be considered for those with intermediate to high CACS. PMID- 26670594 TI - [(18)F]-FDG PET/CT imaging for detection of nodal metastases in patients with squamous cell carcinoma of the pharynx and larynx: comparison with CT. AB - PURPOSE: Our aim was to investigate the diagnostic accuracy of fluorine-18 labeled fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) relative to CT for detecting neck lymph node metastases in patients with squamous cell carcinoma (SCC) of the hypopharynx, oropharynx, and larynx. METHODS: Thirty-four patients with SCC of the hypopharynx (n = 20), oropharynx (n = 5), and larynx (n = 9) who underwent neck dissection (29 bilateral, 5 unilateral; a total of 355 nodal levels) were assessed. Two observers determined the long-axis diameter and maximum standardized uptake value (SUVmax) of all visible neck nodes. Results of FDG-PET/CT were compared with those of corresponding histopathologic examinations according to the neck-level system. RESULTS: Histopathology revealed metastases in 70 of 355 nodal levels. Using a best discriminative SUVmax cutoff of 3.65, sensitivity, specificity, and accuracy of FDG-PET/CT on a level-by-level basis were 72.9, 96.8, and 92.1 %; those for CT were 52.9, 98.6, and 89.6 %. Differences in sensitivity and accuracy were significant (p < 0.01). The best cutoff SUVmax on the ipsilateral side was 4.61, with corresponding figures of 81.6, 100, and 94.7 %; that on the contralateral side was 2.41, with figures of 60, 88.4, and 85.4 %. CONCLUSION: FDG-PET/CT with SUVmax is useful for preoperative evaluation of neck-node metastasis from SCC of the pharynx and larynx, especially on the ipsilateral side. PMID- 26670595 TI - Robust High-performance Dye-sensitized Solar Cells Based on Ionic Liquid sulfolane Composite Electrolytes. AB - Novel ionic liquid-sulfolane composite electrolytes based on the 1,2,3-triazolium family of ionic liquids were developed for dye-sensitized solar cells. The best performing device exhibited a short-circuit current density of 13.4 mA cm(-2), an open-circuit voltage of 713 mV and a fill factor of 0.65, corresponding to an overall power conversion efficiency (PCE) of 6.3%. In addition, these devices are highly stable, retaining more than 95% of the initial device PCE after 1000 hours of light- and heat-stress. These composite electrolytes show great promise for industrial application as they allow for a 14.5% improvement in PCE, compared to the solvent-free eutectic ionic liquid electrolyte system, without compromising device stability. PMID- 26670596 TI - The Mercedes flap and its new variants: a 'workhorse' flap for the dermatological surgeon? AB - BACKGROUND: The plastic reconstruction of defects in problem regions, such as, e.g. the heel, temple, malleolar region, sternum and capillitium, is usually a challenge. OBJECTIVE: We describe the use of the Mercedes flap, a combination of the purse string and advancement flap, and new modifications for use in various body locations. These examples extend the scope of application in tumour surgery of the skin. METHODS: We demonstrate the different techniques and practical application of the repair and evaluate the benefits and limitations. RESULTS: The Mercedes flap and its modifications are an excellent method for repairing various defects in problem locations after tumour surgery of the skin. CONCLUSION: The Mercedes flap and its modifications prove to be a good alternative to other closure types, especially in problem regions such as the shoulder, malleolar region, heel, etc. The procedure is fast and simple, with few side-effects, and proves to be a 'workhorse' flap for the dermatological surgeon. PMID- 26670597 TI - Comprehensively understanding fatigue in patients with myeloproliferative neoplasms. AB - BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS: A 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS: Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001). CONCLUSIONS: The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. PMID- 26670598 TI - Phytochemical Characteristics of Seeds and Its Effects on the Intestinal Motility and Toxicity of Joannesia princeps. AB - Joannesia princeps is a plant commonly used in folk medicine as laxative for menstrual discomfort and as antihelminthic and antimicrobial to reduce edema and improve tissue healing. The seeds are used in many regions of Brazil as laxative; however, studies are needed to confirm its effectiveness and safety. Thus, the aim of this study was to evaluate the effects of using seeds of this plant on intestinal motility of Wistar rats, evaluate the effects and acute toxicity of its management, as well as determine its phytochemical profile. The evaluation of the effect on the intestinal motility was performed according to the model described by Michelin and Salgado (2004) with modifications. For the evaluation of acute toxicity, we used the model described by Craveiro et al. (2008) and Goloni et al. (2005), and for the analysis of the presence of alkaloids, flavonoids, anthraquinones, steroids, and other components, we used the method described by Carvalho et al. (2006). The results showed that J. princeps exhibits laxative effects similar to those of Senna species such as Cassia angustifolia and the phytochemical analysis of ethanol and aqueous extracts showed the presence of alkaloids, triterpenes, and/or steroids compounds. Acute toxicity showed in the first 12 h: piloerection, contortion, decreased respiratory rate, diarrhea, and weight loss. After this period, these changes were no longer observed. It was concluded that the seeds of this plant have potential laxative activity, confirming the popular use and that the dose of 5 g/kg can be considered safe for consumption. PMID- 26670599 TI - Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry? AB - BACKGROUND: Anal manometry is the standard technique for evaluating anal sphincter function. However, the functional lumen imaging probe (EndoFLIP((r)) ) can be used to measure sphincter distensibility during volume-controlled distensions. Our aims were (i) to assess anal distensibility in patients with fecal incontinence (FI) and in healthy subjects using the EndoFLIP((r)) and (ii) to compare the results with anal pressures measured by 3D high-resolution manometry (3D-HRM) to determine whether the EndoFLIP((r)) was more sensitive and specific for diagnosing FI than 3D-HRM. METHODS: EndoFLIP((r)) and 3D-HRM assessments of 34 female FI patients and 40 healthy female subjects were performed. Anal distensibility was measured as the median cross-sectional area at the narrowest point divided by the corresponding intra-bag pressure at rest and during peak voluntary contraction and was expressed in mm(2) /mmHg. KEY RESULTS: A 40-mL anal distensibility index was selected for further comparisons as it provided the best discrimination between the FI patients and the healthy subjects. The index was significantly higher in the FI patients than in the healthy subjects at rest (p = 1.10(-4) ) and during voluntary contraction (p = 1.10(-4) ). The index at rest and during voluntary contraction appeared to be more appropriate than anal pressures for discriminating between FI patients and healthy subjects. CONCLUSIONS & INFERENCES: The present study confirmed that FI is associated with an abnormally high distensibility index at rest and during voluntary contraction. The ability of the distensibility index to discriminate between FI patients and healthy subjects was significantly better than anal pressure. PMID- 26670600 TI - Non-local Optical Topological Transitions and Critical States in Electromagnetic Metamaterials. AB - Just as the topology of the Fermi surface defines the properties of the free electrons in metals and semiconductors, the geometry of the iso-frequency surface in the phase space of the propagating electromagnetic waves, determines the optical properties of the corresponding optical materials. Furthermore, in the direct analog to the Lifshitz transition in condensed matter physics, a change in the topology of iso-frequency surface has a dramatic effect on the emission, propagation and scattering of the electromagnetic waves. Here, we uncover a new class of such optical topological transitions in metamaterials, induced by the non-locality of the electromagnetic response inherent to these composites. PMID- 26670601 TI - Differences in cannabis-related experiences between patients with a first episode of psychosis and controls. AB - BACKGROUND: Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations. METHOD: A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively. RESULTS: Both 'bad' and 'enjoyable' experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population. CONCLUSIONS: These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more 'bad' and 'enjoyable' experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms. PMID- 26670602 TI - Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults. AB - A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia. PMID- 26670603 TI - A 1-Year Study on the Detection of Human Enteric Viruses in New Caledonia. AB - Human enteric viruses occur in high concentrations in wastewater and can contaminate receiving environmental waters. Due to the lack of data on the prevalence of enteric viruses in New Caledonia, the presence and the concentrations of enteric viruses in wastewater and seawater were determined. Untreated wastewater and seawater samples were collected monthly for 1 year from a wastewater treatment plant (WWTP) and from the WWTP's outlet, located directly on a popular recreational beach. Samples were tested for norovirus genogroups I and II (NoV GI and GII), astroviruses (AsV), sapoviruses (SaV), enteroviruses (EV), hepatitis A viruses (HAV), rotaviruses (RoV), human adenoviruses (HAdV) and human polyomaviruses (HPyV). To support these data, faecal samples from cases of gastroenteritis were tested for the first time for NoV and detected in the population. NoV GI, NoV GII, EV, SaV, HAdV and HPyV were detected in all wastewaters, RoV in 75% and AsV in 67%. HAV were not detected in wastewater. Overall, 92% of seawater samples were positive for at least one virus. HPyV were detected most frequently in 92% of samples and at concentrations up to 7.7 * 10(3) genome copies/L. NoV GI, NoV GII, EV, SaV, RoV and HAdV were found in 33, 66, 41, 33, 16 and 66% of seawater samples, respectively. AsV were not detected in seawater. This study reports for the first time the presence of NoV and other enteric viruses in New Caledonia and highlights the year-round presence of enteric viruses in the seawater of a popular beach. PMID- 26670604 TI - Improvement in Open-Circuit Voltage of Thin Film Solar Cells from Aqueous Nanocrystals by Interface Engineering. AB - In this work, improved solar cells from aqueous CdTe NCs is achieved by replacing evaporated MoOx with spiro-OMeTAD as a hole transfer layer. The increased Voc and Jsc can be attributed to interfacial dipole effect and reduced back recombination loss, respectively. A high PCE of 6.56% for solar cells from aqueous NCs is obtained by optimizing the microstructure further. PMID- 26670605 TI - Ex vivo evaluation of new 2D and 3D dental radiographic technology for detecting caries. AB - OBJECTIVES: Proximal dental caries remains a prevalent disease with only modest detection rates by current diagnostic systems. Many new systems are available without controlled validation of diagnostic efficacy. The objective of this study was to evaluate the diagnostic efficacy of three potentially promising new imaging systems. METHODS: This study evaluated the caries detection efficacy of Schick 33 (Sirona Dental, Salzburg, Austria) intraoral digital detector images employing an advanced sharpening filter, Planmeca ProMax((r)) (Planmeca Inc., Helsinki, Finland) extraoral "panoramic bitewing" images and Sirona Orthophos XG3D (Sirona Dental) CBCT images with advanced artefact reduction. Conventional photostimulable phosphor images served as the control modality. An ex vivo study design using extracted human teeth, ten expert observers and micro-CT ground truth was employed. RESULTS: Receiver operating characteristic analysis indicated similar diagnostic efficacy of all systems (ANOVA p > 0.05). The sensitivity of the Schick 33 images (0.48) was significantly lower than the other modalities (0.53-0.62). The specificity of the Planmeca images (0.86) was significantly lower than Schick 33 (0.96) and XG3D (0.97). The XG3D showed significantly better cavitation detection sensitivity (0.62) than the other modalities (0.48-0.57). CONCLUSIONS: The Schick 33 images demonstrated reduced caries sensitivity, whereas the Planmeca panoramic bitewing images demonstrated reduced specificity. XG3D with artefact reduction demonstrated elevated sensitivity and specificity for caries detection, improved depth accuracy and substantially improved cavitation detection. Care must be taken to recognize potential false-positive caries lesions with Planmeca panoramic bitewing images. Use of CBCT for caries detection must be carefully balanced with the presence of metal artefacts, time commitment, financial cost and radiation dose. PMID- 26670606 TI - Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis. AB - Apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. In the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (MCL-1) is exploited by the intra-macrophage parasite Leishmania donovani to protect their "home" from actinomycin D-induced mitochondria-dependent apoptosis. Among all the anti-apoptotic BCL-2 family members, infection preferentially up-regulated expression of MCL-1 at both the mRNA and protein levels and compared with infected control, MCL-1-silenced infected macrophages documented enhanced caspase activity and increased apoptosis when subjected to actinomycin D treatment. Phosphorylation kinetics and ChIP assay demonstrated that infection-induced MCL-1 expression was regulated by transcription factor CREB (cAMP-response element-binding protein) and silencing of CREB resulted in reduced expression of MCL-1 and increased apoptosis. During infection, MCL-1 was found to be localized in mitochondria and this was significantly reduced in Tom70-silenced macrophages, suggesting the active role of TOM70 in MCL-1 transport. In the mitochondria, MCL-1 interacts with the major pro-apoptotic protein BAK and prevents BAK-BAK homo-oligomer formation thereby preventing cytochrome c release-mediated mitochondrial dysfunction. Silencing of MCL-1 in the spleen of infected mice showed decreased parasite burden and increased induction of splenocyte apoptosis. Collectively our results showed that L. donovani exploited the macrophage anti-apoptotic protein MCL-1 to prevent BAK mediated mitochondria-dependent apoptosis thereby protecting its niche, which is essential for disease progression. PMID- 26670608 TI - Involvement of Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts. AB - Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-kappaB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. PMID- 26670609 TI - A Novel Serpin Regulatory Mechanism: SerpinB9 IS REVERSIBLY INHIBITED BY VICINAL DISULFIDE BOND FORMATION IN THE REACTIVE CENTER LOOP. AB - The intracellular protease inhibitor Sb9 (SerpinB9) is a regulator of the cytotoxic lymphocyte protease GzmB (granzyme B). Although GzmB is primarily involved in the destruction of compromised cells, recent evidence suggests that it is also involved in lysosome-mediated death of the cytotoxic lymphocyte itself. Sb9 protects the cell from GzmB released from lysosomes into the cytosol. Here we show that reactive oxygen species (ROS) generated within cytotoxic lymphocytes by receptor stimulation are required for lyososomal permeabilization and release of GzmB into the cytosol. Importantly, ROS also inactivate Sb9 by oxidizing a highly conserved cysteine pair (P1-P1' in rodents and P1'-P2' in other mammals) in the reactive center loop to form a vicinal disulfide bond. Replacement of the P4-P3' reactive center loop residues of the prototype serpin, SERPINA1, with the P4-P5' residues of Sb9 containing the cysteine pair is sufficient to convert SERPINA1 into a ROS-sensitive GzmB inhibitor. Conversion of the cysteine pair to serines in either human or mouse Sb9 results in a functional serpin that inhibits GzmB and resists ROS inactivation. We conclude that ROS sensitivity of Sb9 allows the threshold for GzmB-mediated suicide to be lowered, as part of a conserved post-translational homeostatic mechanism regulating lymphocyte numbers or activity. It follows, for example, that antioxidants may improve NK cell viability in adoptive immunotherapy applications by stabilizing Sb9. PMID- 26670607 TI - High Affinity Heme Binding to a Heme Regulatory Motif on the Nuclear Receptor Rev erbbeta Leads to Its Degradation and Indirectly Regulates Its Interaction with Nuclear Receptor Corepressor. AB - Rev-erbalpha and Rev-erbbeta are heme-binding nuclear receptors (NR) that repress the transcription of genes involved in regulating metabolism, inflammation, and the circadian clock. Previous gene expression and co-immunoprecipitation studies led to a model in which heme binding to Rev-erbalpha recruits nuclear receptor corepressor 1 (NCoR1) into an active repressor complex. However, in contradiction, biochemical and crystallographic studies have shown that heme decreases the affinity of the ligand-binding domain of Rev-erb NRs for NCoR1 peptides. One explanation for this discrepancy is that the ligand-binding domain and NCoR1 peptides used for in vitro studies cannot replicate the key features of the full-length proteins used in cellular studies. However, the combined in vitro and cellular results described here demonstrate that heme does not directly promote interactions between full-length Rev-erbbeta (FLRev-erbbeta) and an NCoR1 construct encompassing all three NR interaction domains. NCoR1 tightly binds both apo- and heme-replete FLRev-erbbeta.DNA complexes; furthermore, heme, at high concentrations, destabilizes the FLRev-erbbeta.NCoR1 complex. The interaction between FLRev-erbbeta and NCoR1 as well as Rev-erbbeta repression at the Bmal1 promoter appear to be modulated by another cellular factor(s), at least one of which is related to the ubiquitin-proteasome pathway. Our studies suggest that heme is involved in regulating the degradation of Rev-erbbeta in a manner consistent with its role in circadian rhythm maintenance. Finally, the very slow rate constant (10(-6) s(-1)) of heme dissociation from Rev-erbbeta rules out a prior proposal that Rev-erbbeta acts as an intracellular heme sensor. PMID- 26670610 TI - Starvation Induces Proteasome Autophagy with Different Pathways for Core and Regulatory Particles. AB - The proteasome is responsible for the degradation of many cellular proteins. If and how this abundant and normally stable complex is degraded by cells is largely unknown. Here we show that in yeast, upon nitrogen starvation, proteasomes are targeted for vacuolar degradation through autophagy. Using GFP-tagged proteasome subunits, we observed that autophagy of a core particle (CP) subunit depends on the deubiquitinating enzyme Ubp3, although a regulatory particle (RP) subunit does not. Furthermore, upon blocking of autophagy, RP remained largely nuclear, although CP largely localized to the cytosol as well as granular structures within the cytosol. In all, our data reveal a regulated process for the removal of proteasomes upon nitrogen starvation. This process involves CP and RP dissociation, nuclear export, and independent vacuolar targeting of CP and RP. Thus, in addition to the well characterized transcriptional up-regulation of genes encoding proteasome subunits, cells are also capable of down-regulating cellular levels of proteasomes through proteaphagy. PMID- 26670611 TI - Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice. AB - Impairment of myocardial fatty acid substrate metabolism is characteristic of late-stage heart failure and has limited treatment options. Here, we investigated whether inhibition of G-protein-coupled receptor kinase 2 (GRK2) could counteract the disturbed substrate metabolism of late-stage heart failure. The heart failure like substrate metabolism was reproduced in a novel transgenic model of myocardium-specific expression of fatty acid synthase (FASN), the major palmitate synthesizing enzyme. The increased fatty acid utilization of FASN transgenic neonatal cardiomyocytes rapidly switched to a heart failure phenotype in an adult like lipogenic milieu. Similarly, adult FASN transgenic mice developed signs of heart failure. The development of disturbed substrate utilization of FASN transgenic cardiomyocytes and signs of heart failure were retarded by the transgenic expression of GRKInh, a peptide inhibitor of GRK2. Cardioprotective GRK2 inhibition required an intact ERK axis, which blunted the induction of cardiotoxic transcripts, in part by enhanced serine 273 phosphorylation of Pparg (peroxisome proliferator-activated receptor gamma). Conversely, the dual-specific GRK2 and ERK cascade inhibitor, RKIP (Raf kinase inhibitor protein), triggered dysfunctional cardiomyocyte energetics and the expression of heart failure promoting Pparg-regulated genes. Thus, GRK2 inhibition is a novel approach that targets the dysfunctional substrate metabolism of the failing heart. PMID- 26670612 TI - Telomere mean length in patients with diabetic retinopathy. AB - Telomere regression has been shown to be associated with several complex disorders like diabetes mellitus, cancer, cataract etc. Diabetic retinopathy develops as a complication of chronic hyperglycemia leading to increased oxidative stress that may potentially lead to shortening of telomeres. We sought to determine whether there is any association between telomere mean length (TML) of peripheral blood monocytes with the presence and severity of diabetic retinopathy. The study involved 120 subjects, comprising 27 non-insulin dependent diabetes mellitus (NIDDM) without any diabetic retinopathy (NDR), 45 NIDDM subjects with non-proliferative diabetic retinopathy (NPDR), 12 NIDDM subjects with proliferative diabetic retinopathy (PDR) and 36 healthy controls. Determination of TML of the study subjects was performed by Southern hybridization using telomere probe. Among the biochemical parameters, HBA1c showed a negative correlation with shortened telomeres in the PDR subjects. However, telomere length was positively correlated with high density lipo protein (HDL) in the control subjects. The control group had significantly greater TML as compared to the rest of the groups and the NDR subjects with NPDR and PDR had substantially decreased TML than the NIDDM subjects without retinopathy. PMID- 26670614 TI - The Efficacy of Pregabalin in the Treatment of Prediabetic Neuropathic Pain. AB - OBJECTIVE: We report the results of a pilot, enrichment-design, placebo controlled crossover trial of pregabalin for the treatment of prediabetic small fiber neuropathic pain. METHODS: Individuals with impaired fasting glucose or impaired glucose tolerance and neuropathic pain were evaluated according to UTAH Early Neuropathy Scale (UENS), Quantitative Sensory Testing, and intraepidermal nerve fiber density (IENFD). Symptoms were graded according to the Numeric Rating Scale (NRS). Individuals who responded to the administration of placebo were not eligible. Pregabalin was initiated at a dose of 75 mg qid and tapered up to 300 mg bid. Only individuals with a reduction of pain scores >=30% were eligible to continue with the double-blind phase, which consisted of a randomized crossover period of 1 month of pregabalin and 1 month of placebo, with 7 days of washout between periods. RESULTS: Forty-five participants were enrolled in the study. There was 36% reduction in the NRS from baseline after 1 month of single-blind pregabalin (NRS=5.1+/-2.6). Twenty-six participants were eligible for the double blind phase. There was further reduction of pain in the double-blind pregabalin and the placebo groups, but the pregabalin group had a statistically significant reduction of pain (NRS=3.2+/-2.2 vs. 4.0+/-2; P<0.05). Participants who did not respond showed a lower IENFD than those who responded, suggesting more severe nerve damage. CONCLUSIONS: This pilot study showed improvement of prediabetic neuropathic pain. Participants with higher pain scores at baseline had higher UENS scores and a lower IENFD. Limitations of the study include the small number of participants and the carry-over effect. PMID- 26670615 TI - Risk of Opioid Abuse and Biopsychosocial Characteristics Associated With This Risk Among Chronic Pain Patients Attending a Multidisciplinary Pain Treatment Facility. AB - OBJECTIVES: The objectives of this study were to (1) determine the proportion of patients referred to a multidisciplinary pain treatment facility at risk of opioid abuse, (2) examine biopsychosocial factors associated with this risk, and (3) compare patient outcomes 6 months later across risk of opioid abuse and type of treatment (opioids vs. no opioids). METHODS: Participants were 3040 patients (mean age=53.3+/-14.7 y; female=56%) enrolled in the Quebec Pain Registry between July 2012 and May 2014. Patients answered self-report and nurse-administered questionnaires (pain and psychosocial constructs, Opioid Risk Tool, pain medication, etc.) before initiating treatment at the multidisciplinary pain treatment facility and 6 months later. Data were analyzed using the Pearson chi tests, multivariable binary logistic regression, and multivariate general linear model. RESULTS: Results showed that 81%, 13%, and 6% of patients were at low, moderate, and severe risk of opioid abuse, respectively. Civil status, pain duration, mental health-related quality of life, and cigarette smoking were significantly associated with risk of opioid abuse (P<0.001). There was a significant interaction between risk of opioid abuse and type of treatment in predicting 6-month pain outcomes and quality of life. DISCUSSION: Almost 20% of patients had a moderate/severe risk of opioid abuse; whether these patients were taking opioids or not for their pain, they had worse outcomes at follow-up. These results point to the importance of assessing risk of opioid abuse in chronic pain patients and to consider how this risk may impact on their clinical evolution. PMID- 26670613 TI - VdNUC-2, the Key Regulator of Phosphate Responsive Signaling Pathway, Is Required for Verticillium dahliae Infection. AB - In fungal cells, a phosphate (Pi) responsive signaling and metabolism (PHO) pathway regulates Pi-homeostasis. NUC-2/PHO81 and its homologs are one of the most important components in the regulation pathway. In soil-borne phytopathogenic fungus Verticillium dahliae, we identified a Neurospora crassa nuc-2 homolog gene VdNUC-2. VdNUC-2 is composed of 1,018 amino acids, and is highly conserved in tested filamentous fungi. Under conditions of Pi-starvation, compared with the wild-type strain and ectopic complementation strains, the VdNUC 2 knocked out mutants exhibited reduced radial growth, decreased production of conidia and microsclerotia, and were more sensitive to hydrogen peroxide stress. The virulence of VdNUC-2 defective mutants was significantly compromised, and that was unable to be restored by exogenous application of extra Pi. Additionally, the deletion mutants of VdNUC-1, a key transcription factor gene positively controlled by VdNUC-2 in the PHO pathway, showed the similar cultural phenotypes as VdNUC-2 mutants when both of them grew in Pi-limited conditions. However, the virulence of VdNUC-1 mutants was comparable to the wild-type strain. These evidences indicated that the virulence reduction in VdNUC-2 mutants is not due to the interruptions in the PHO pathway or the disturbance of Pi-homeostasis in V. dahliae cytoplasm. VdNUC-2 is not only a crucial gene in the PHO pathway in V. dahliae, but also is required for the full virulence during host-infection. PMID- 26670616 TI - The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis. AB - OBJECTIVE: To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis. METHODS: A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model. RESULTS: Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster infection. CONCLUSIONS: Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. Larger RCTs with longer duration of observation are necessary to provide strong evidence of the efficacy and safety of leflunomide in LN patients. PMID- 26670618 TI - New option for primary stroke prevention in sickle cell anaemia. PMID- 26670617 TI - Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. AB - BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (>= 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non inferiority margin set at 15 cm/s. The primary analysis was done in the intention to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4.54 (0.10-8.98). Non-inferiority (p=8.82 * 10(-16)) and post-hoc superiority (p=0.023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health. PMID- 26670619 TI - Fluorine-18 patents (2009-2015). Part 1: novel radiotracers. AB - The most commonly utilized PET radionuclide is fluorine-18 ((18)F) because of its convenient half-life and excellent imaging properties. In this review, we present the first analysis of patents issued for radiotracers labeled with fluorine-18 (between 2009 and 2015), and provide perspective on current trends and future directions in PET radiotracer development. PMID- 26670621 TI - Effect of Therapeutic Hypothermia on Survival to Hospital Discharge in Out-of hospital Cardiac Arrest Secondary to Nonshockable Rhythms. AB - OBJECTIVES: Therapeutic hypothermia has been shown to improve neurologic outcome and survival in out-of-hospital cardiac arrest (OHCA) following return of spontaneous circulation (ROSC), and current guidelines recommend therapeutic hypothermia for all comatose survivors of OHCA. However, recommendations for nonshockable rhythms are not as strongly supported. Our study aims to provide further evidence on the use of therapeutic hypothermia in nonshockable rhythms. METHODS: A multivariate analysis with propensity score matching was performed using a cardiac arrest registry maintained by the Houston Fire Department. The analysis was limited to adult patients achieving ROSC following OHCA secondary to nonshockable rhythm in Houston from 2007 to 2012 with definitive information regarding the implementation of therapeutic hypothermia. The primary outcome was survival to hospital discharge. RESULTS: Of 9,479 records identified for analysis, 7,839 had an initial nonshockable rhythm. Of these, 2,609 (33.3%) had sustained ROSC and 1,768 (22.6%) were admitted to the hospital. Data on therapeutic hypothermia use were available for 696 patients, with 335 (48.1%) receiving therapeutic hypothermia. Propensity score matching yielded 260 case/control pairs. The odds of survival to hospital discharge was an odds ratio of 1.07 (95% confidence interval = 0.71 to 1.60) for those in the therapeutic hypothermia group versus the nontherapeutic hypothermia group (p = 0.79). CONCLUSIONS: Based on this retrospective study, therapeutic hypothermia is not associated with improved survival in patients with OHCA secondary to nonshockable rhythms. Given the limitations of our study, further prospective trials to assess the effect of therapeutic hypothermia for OHCA with nonshockable rhythms are warranted. PMID- 26670620 TI - New Infestin-4 Mutants with Increased Selectivity against Factor XIIa. AB - Factor XIIa (fXIIa) is a serine protease that triggers the coagulation contact pathway and plays a role in thrombosis. Because it interferes with coagulation testing, the need to inhibit fXIIa exists in many cases. Infestin-4 (Inf4) is a Kazal-type inhibitor of fXIIa. Its specificity for fXIIa can be enhanced by point mutations in the protease-binding loop. We attempted to adapt Inf4 for the selective repression of the contact pathway under various in vitro conditions, e.g., during blood collection and in 'global' assays of tissue factor (TF) dependent coagulation. First, we designed a set of new Inf4 mutants that, in contrast to wt-Inf4, had stabilized canonical conformations during molecular dynamics simulation. Off-target activities against factor Xa (fXa), plasmin, and other coagulation proteases were either reduced or eliminated in these recombinant mutants, as demonstrated by chromogenic assays. Interactions with fXIIa and fXa were also analyzed using protein-protein docking. Next, Mutant B, one of the most potent mutants (its Ki for fXIIa is 0.7 nM) was tested in plasma. At concentrations 5-20 MUM, this mutant delayed the contact-activated generation of thrombin, as well as clotting in thromboelastography and thrombodynamics assays. In these assays, Mutant B did not affect coagulation initiated by TF, thus demonstrating sufficient selectivity and its potential practical significance as a reagent for coagulation diagnostics. PMID- 26670622 TI - Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner. AB - MicroRNAs are short (17-26) noncoding RNAs driving or modulating physiological and pathological cellular events. Overexpression of miR-155 is pathogenic in B cell malignancy but was also reported in a number of solid tumors-in particular, in breast cancer, where its role remains unclear and often contradictory. Using representative cell line models, we sought to determine whether the discrepant miR-155 effects in breast cancer could be explained by the heterogeneity of the disease. The growth of six breast cancer cell lines transfected with several miRNA mimics was analyzed. We found MCF-7 cell growth to be inhibited by miR-155 and miR-145 mimics, both 23-nt long, but not by a number of shorter mimics, including a universal commercial negative control. Microarray and Western blot analyses revealed induction of apoptosis, associated with interferon-beta after activation of the double-stranded RNA sensor pathway. 3' Trimming of the miRNA mimics to 21 nt substantially reduced their growth-inhibitory potency. Mutating the canonical seed of the miR-155 mimic had no effect on the induced inhibition, which was abolished by mutating the miRNA seed of the artificial passenger strand. A panel of breast cancer cell lines showed a wide range of sensitivities to 23-mer mimics, broadly consistent with the sensitivity of the cell lines to Poly (I:C). We demonstrate two sources for nonspecific in vitro effects by miRNA mimics: duplex length and the artificial passenger strand. We highlight the danger of a universal 21-mer negative control and the importance of using matched seed mutants for reliable interpretation of phenotypes. PMID- 26670623 TI - Nearly 1000 Protein Identifications from 50 ng of Xenopus laevis Zygote Homogenate Using Online Sample Preparation on a Strong Cation Exchange Monolith Based Microreactor Coupled with Capillary Zone Electrophoresis. AB - A sulfonate-silica hybrid strong cation exchange monolith microreactor was synthesized and coupled to a linear polyacrylamide coated capillary for online sample preparation and capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) bottom-up proteomic analysis. The protein sample was loaded onto the microreactor in an acidic buffer. After online reduction, alkylation, and digestion with trypsin, the digests were eluted with 200 mM ammonium bicarbonate at pH 8.2 for CZE-MS/MS analysis using 1 M acetic acid as the background electrolyte. This combination of basic elution and acidic background electrolytes results in both sample stacking and formation of a dynamic pH junction. 369 protein groups and 1274 peptides were identified from 50 ng of Xenopus laevis zygote homogenate, which is comparable with an offline sample preparation method, but the time required for sample preparation was decreased from over 24 h to less than 40 min. Dramatically improved performance was produced by coupling the reactor to a longer separation capillary (~100 cm) and a Q Exactive HF mass spectrometer. 975 protein groups and 3749 peptides were identified from 50 ng of Xenopus protein using the online sample preparation method. PMID- 26670624 TI - An evaluation of paediatric medicines reconciliation at hospital discharge into the community. AB - OBJECTIVE: A UK national survey of primary care physicians has indicated that the medication information on hospital discharge summary was incomplete or inaccurate most of the time. Internationally, studies have shown that hospital pharmacist's interventions reduce these discrepancies in the adult population. There have been no published studies on the incidence and severity of the discrepancies of the medication prescribed for children specifically at discharge to date. The objectives of this study were to investigate the incidence, nature and potential clinical severity of medication discrepancies at the point of hospital discharge in a paediatric setting. METHODS: Five weeks prospective review of hospital discharge letters was carried out. Medication discrepancies between the initial doctor's discharge letter and finalised drug chart were identified, pharmacist changes were recorded and their severity was assessed. The setting of the review was at a London, UK paediatric hospital providing local secondary and specialist tertiary care. The outcome measures were: - incidence and the potential clinical severity of medication discrepancies identified by the hospital pharmacist at discharge. KEY FINDINGS: 142 patients (64 female and 78 males, age range 1 month 18 years) were discharged on 501 medications. The majority of patients were under the care of general surgery and general paediatric teams. One in three discharge letters contained at least one medication discrepancy and required pharmacist interventions to rectify prior to completion. Of these, 1 in 10 had the potential for patient harm if undetected. CONCLUSIONS: Medicines reconciliation by pharmacist at discharge may be a good intervention in preventing medication discrepancies which have the potential to cause moderate harm in paediatric patients. PMID- 26670625 TI - Thermoradiotherapy planning: Integration in routine clinical practice. AB - Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to ~10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients. PMID- 26670626 TI - Provider Distribution Changes in Dual-Energy X-Ray Absorptiometry in the Medicare Population Over the Past Decade. AB - Both radiologists as well as nonimaging physicians perform dual-energy X-ray absorptiometry (DXA) imaging in the United States. This study aims to compare provider distribution between these physician groups on the Medicare population, which is the predominant age group of patients evaluated by this imaging procedure. Using the 2 relevant Current Procedural Terminology, Fourth Edition codes for DXA scans, source data were obtained from the CMS Physician Supplier Procedure Summary Master Files from 2003 through 2013. DXA scan procedure volumes for radiologists and nonradiologists on Medicare patients were tabulated. Utilization rates were calculated. From 2003 to 2013, the total number of DXA scans performed on Medicare patients decreased by 2%. However, over the same period, the number of scans performed by radiologists had increased by 25% over nonimaging specialists, whose utilization had declined by approximately the same amount. From 2003 to 2013, the rate of utilization of DXA scans in the Medicare fee-for-service population declined somewhat. However, radiologists continue to gain market share from other specialists and now predominate in this type of imaging by a substantial margin. PMID- 26670627 TI - High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. AB - AIM: High iron measured using dietary intake and biomarkers is associated with Type 2 diabetes. It is uncertain whether a similar association exists for gestational diabetes mellitus. The aim of this systematic review was to conduct a cohort study examining first trimester body iron stores and subsequent risk of gestational diabetes, and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of gestational diabetes. METHODS: Serum samples from women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and gestational diabetes diagnosis. Blood was analysed for ferritin, soluble transferrin receptor and C reactive protein. Associations between iron biomarkers and gestational diabetes were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included studies of all designs published in English from January 1995 to July 2015 that examined the association between iron and gestational diabetes and included an appropriate comparison group. RESULTS: Of 3776 women, 3.4% subsequently developed gestational diabetes. Adjusted analyses found increased odds of gestational diabetes for ferritin (OR 1.41; 95% CI 1.11, 1.78), but not for soluble transferrin receptor (OR 1.00; 95% CI 0.97, 1.03) per unit increase of the biomarker. Two trials of iron supplementation found no association with gestational diabetes. Increased risk of gestational diabetes was associated with higher levels of ferritin and serum iron and dietary haem iron intakes. CONCLUSIONS: Increased risk of gestational diabetes among women with high serum ferritin and iron levels and dietary haem iron intakes warrants further investigation. PMID- 26670628 TI - After After Tiller: the impact of a documentary film on understandings of third trimester abortion. AB - Onscreen pseudo-experiences have been shown to influence public perceptions of contested social issues. However, research has not considered whether such experiences have limits in their influence and/or vary in their impact. Using the case of third-trimester abortion, an issue subject to high amounts of misinformation, low public support and low occurrence in the general population, we investigate how the pseudo-experience of viewing After Tiller, a documentary film showing stories of third-trimester abortion, providers and patients, might serve as a counterpoint to misinformation and myth. We interviewed 49 viewers to assess how viewing the film interacted with viewers' previously held understandings of later abortion. Participants reported that viewing made them feel more knowledgeable about later-abortion patients and providers and increased their support for legal third-trimester abortion access, suggesting the efficacy of this pseudo-experience in changing belief. Nonetheless, respondents' belief systems were not entirely remade and the effects of the film varied, particularly in regards to gatekeeping around the procedure and the reasons why women seek later abortion. Findings show the potential of onscreen pseudo-experiences as a means for social change, but also reveal their limits and varying impacts. PMID- 26670629 TI - Responding to the 2014 Ebola Outbreak: The Value of Effective Interprofessional Communication During Emergency Response. PMID- 26670630 TI - Half-dose photodynamic therapy followed by diode micropulse laser therapy as treatment for chronic central serous chorioretinopathy: evaluation of a prospective treatment protocol. AB - PURPOSE: To evaluate the outcome of a prospective protocol for the treatment of chronic central serous chorioretinopathy (CSC). METHODS: Interventional prospective case series in 59 eyes (59 patients) with active chronic CSC. All patients were first treated with indocyanine green angiography (ICGA)-guided half dose photodynamic therapy (PDT). In case of persistent serous subretinal fluid (SRF) after a follow-up period of at least 6 weeks, ICGA-guided PDT was repeated. If the SRF persisted after two PDT treatments, additional ICGA-guided high density subthreshold diode micropulse laser (HSML) therapy was performed. Clinical evaluation included best-corrected visual acuity (BCVA), fundoscopy, OCT, fundus autofluorescence, fluorescein angiography and ICGA. RESULTS: After a single PDT treatment, complete resolution of SRF was seen in 37 of 59 eyes. Of the 22 eyes with no complete resolution of SRF, 19 eyes received a second PDT treatment, after which seven eyes of the 19 eyes showed a complete resolution of SRF. Ten eyes underwent HSML, of which one eye had complete resolution of SRF within 7 weeks. At final follow-up a complete resolution of SRF was present in 80% of all eyes. The mean BCVA improved from 0.28 logMAR at baseline to 0.16 logMAR at final follow-up. Improvement of BCVA was highest after the first treatment (-0.12 logMAR, p < 0.001). CONCLUSIONS: The proposed treatment strategy using half-dose PDT and HSML in active chronic CSC resulted in an anatomical success rate of 80%. The first half-dose PDT treatment has the highest likelihood of a favourable treatment response on OCT and BCVA increase. PMID- 26670631 TI - Stability of trauma-related symptoms during acute substance use treatment. AB - It is unclear whether post-traumatic stress disorder symptoms and reports of traumatic childhood experiences decline during substance withdrawal. A convenience sample of 34 inpatients of the Psychiatric University Clinics in Basel was recruited and general psychopathological and trauma-related symptoms were assessed with the Brief Symptom Checklist, Post-Traumatic Stress Diagnostic Scale, and Childhood Trauma Questionnaire in the 1st and 3rd week of substance use treatment. The average age of the sample was 41.9 (SD = 9.1) years, and 26.5% were female. Hyperarousal (Mt1 = 4.51 versus Mt2 = 3.61; z = -2.38, p = .017) and avoidance symptoms (Mt1 = 6.24 versus Mt2 = 4.27; z = -2.59, p = .010) declined significantly, but re-experiencing symptoms (Mt1 = 4.00 versus Mt2 = 3.45; z = .50, p = .617) did not. Post-traumatic stress disorder assessment, according to the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria, remained constant for 28 of 34 patients. Likewise, self-reported childhood trauma experiences decreased, yet the number of elevated subscale scores remained stable. Post-traumatic stress disorder symptoms are not adequately treated by substance withdrawal alone. Trauma-specific diagnostics can be initiated with sufficient quality as early as the first week of withdrawal treatment. PMID- 26670633 TI - von Willebrand factor is dimerized by protein disulfide isomerase. AB - Multimeric von Willebrand factor (VWF) is essential for primary hemostasis. The biosynthesis of VWF high-molecular-weight multimers requires spatial separation of each step because of varying pH value requirements. VWF is dimerized in the endoplasmic reticulum by formation of disulfide bonds between the C-terminal cysteine knot (CK) domains of 2 monomers. Here, we investigated the basic question of which protein catalyzes the dimerization. We examined the putative interaction of VWF and the protein disulfide isomerase PDIA1, which has previously been used to visualize endoplasmic reticulum localization of VWF. Excitingly, we were able to visualize the PDI-VWF dimer complex by high resolution stochastic optical reconstruction microscopy and atomic force microscopy. We proved and quantified direct binding of PDIA1 to VWF, using microscale thermophoresis and fluorescence correlation spectroscopy (dissociation constants KD = 236 +/- 66 nM and KD = 282 +/- 123 nM by microscale thermophoresis and fluorescence correlation spectroscopy, respectively). The similar KD (258 +/- 104 nM) measured for PDI interaction with the isolated CK domain and the atomic force microscopy images strongly indicate that PDIA1 binds exclusively to the CK domain, suggesting a key role of PDIA1 in VWF dimerization. On the basis of protein-protein docking and molecular dynamics simulations, combined with fluorescence microscopy studies of VWF CK-domain mutants, we suggest the following mechanism of VWF dimerization: PDI initiates VWF dimerization by forming the first 2 disulfide bonds Cys2771-2773' and Cys2771'-2773. Subsequently, the third bond, Cys2811-2811', is formed, presumably to protect the first 2 bonds from reduction, thereby rendering dimerization irreversible. This study deepens our understanding of the mechanism of VWF dimerization and the pathophysiological consequences of its inhibition. PMID- 26670632 TI - Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. AB - We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1 year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD. PMID- 26670636 TI - Forster resonance energy transfer mediated enhancement of the fluorescence lifetime of organic fluorophores to the millisecond range by coupling to Mn-doped CdS/ZnS quantum dots. AB - Manganese-doped CdS/ZnS quantum dots have been used as energy donors in a Forster like resonance energy transfer (FRET) process to enhance the effective lifetime of organic fluorophores. It was possible to tune the effective lifetime of the fluorophores by about six orders of magnitude from the nanosecond (ns) up to the millisecond (ms) region. Undoped and Mn-doped CdS/ZnS quantum dots functionalized with different dye molecules were selected as a model system for investigating the multiple energy transfer process and the specific interaction between Mn ions and the attached dye molecules. While the lifetime of the free dye molecules was about 5 ns, their linking to undoped CdS/ZnS quantum dots led to a long effective lifetime of about 150 ns, following a non-exponential transient. Manganese-doped core-shell quantum dots further enhanced the long-lasting decay time of the dye to several ms. This opens up a pathway to analyse different fluorophores in the time domain with equal spectral emissions. Such lifetime multiplexing would be an interesting alternative to the commonly used spectral multiplexing in fluorescence detection schemes. PMID- 26670634 TI - Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. AB - The development and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) requires the balanced reconstitution of donor-derived CD4 regulatory T cells (CD4Tregs) as well as effector CD4 (conventional CD4 T cells [CD4Tcons]) and CD8 T cells. To characterize the complex mechanisms that lead to unbalanced recovery of these distinct T-cell populations, we studied 107 adult patients who received T-replete stem cell grafts after reduced-intensity conditioning. Immune reconstitution of CD4Treg, CD4Tcon, and CD8 T cells was monitored for a 2-year period. CD3 T-cell counts gradually recovered to normal levels during this period but CD8 T cells recovered more rapidly than either CD4Tregs or CD4Tcons. Reconstituting CD4Tregs and CD4Tcons were predominantly central memory (CM) and effector memory (EM) cells and CD8 T cells were predominantly terminal EM cells. Thymic generation of naive CD4Tcon and CD8 T cells was maintained but thymic production of CD4Tregs was markedly decreased with little recovery during the 2-year study. T-cell proliferation was skewed in favor of CM and EM CD4Tcon and CD8 T cells, especially 6 to 12 months after HSCT. Intracellular expression of BCL2 was increased in CD4Tcon and CD8 T cells in the first 3 to 6 months after HSCT. Early recovery of naive and CM fractions within each T-cell population 3 months after transplant was also strongly correlated with the subsequent development of chronic graft-versus-host disease (GVHD). These dynamic imbalances favor the production, expansion, and persistence of effector T cells over CD4Tregs and were associated with the development of chronic GVHD. PMID- 26670641 TI - Selective Coupling of Click Anchors to Proteins via Trypsiligase. AB - The combination of pure chemical methods with enzymatic approaches offers a kit system with maximum flexibility for site-specifically tagging proteins with a broad variety of artificial structures. Trypsiligase, a recently introduced designer enzyme for both N- and C-terminal site-specific labeling of peptides and proteins, has been used to introduce click anchors into the human protein cyclophilin 18 and the antibody Fab fragments anti-TNFalpha and anti-Her2. The subsequent click reactions with tetrazine or norbornene moieties lead to quantitative conversions to the corresponding dihydropyridazine products, thereby forming a stable covalent linkage between the label and the protein of interest. With this technology, cyclophilin 18 has been efficiently modified with the fluorescent dansyl moiety and the pharmaceutically relevant polymer PEG exclusively at its N-terminus. With the same methodology, the Fab fragments of anti-TNFalpha and anti-Her2 were derivatized exclusively at their C-terminal ends with PEG and the fluorescent dye carboxyfluorescein in the case of anti-TNFalpha or with the cytotoxic payload DM1 in the case of anti-Her2, to form a homogeneous antibody-drug conjugate (ADC). PMID- 26670644 TI - An unusual complication occurring after cardiac radiofrequency ablation: the devil wears DRESS. PMID- 26670643 TI - Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure. AB - AIMS: We sought to compare the prognostic utility of growth hormone (GH) with NT proBNP) and the ADHERE score in a large cohort of acute heart failure (HF) patients, subcategorized into HF with reduced EF <50% (HFrEF) and preserved EF >=50% (HFpEF). METHODS AND RESULTS: GH and NTproBNP levels were measured in 537 patients (HFrEF n = 415; HFpEF n = 122) with acute HF recruited into this prospective cohort study. The main outcome measure was death or HF readmission at 1 year. GH levels were higher in both HFrEF [1.26 (0.54-2.62) vs. 0.8 (0.26-1.94) ng/mL, P < 0.001] and HFpEF [1.04 (0.48-2.92) vs. 0.53 (0.18-1.94) ng/mL, P = 0.020] patients with the outcome compared with event-free survivors. GH levels were independently predictive for the outcome at 1 year in the entire cohort [HR 1.47, 95% confidence interval (CI) 1.16-1.86, P = 0.001] and those with HFrEF (HR 1.54, 95% CI 1.19-1.99, P = 0.001) in multivariate Cox hazard analysis. GH improved risk classification as measured by continuous net reclassification improvement (NRI) when added to the ADHERE multivariate logistic model of age, sex, urea, heart rate, and systolic blood pressure, for all patients [NRI 29.6 (12.1-47.1), P = 0.001] and HFrEF NRI 21.7 (1.9-41.6), P = 0.034] patients, as well as in addition to the ADHERE model combined with NT-proBNP for all patients [NRI 25.4 (7.8-43.1), P = 0.005]. CONCLUSIONS: GH offers incremental prognostic information over the ADHERE score clinical predictors and NT-proBNP for risk stratification of acute HF patients. PMID- 26670642 TI - Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola. AB - BACKGROUND: Drug resistance in Plasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem((r))). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ~99%. METHODS: 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR-RFLP and sequencing for pfk13-propeller genotype. RESULTS: The cure rate was 91.3%. The obtained results showed that from 103 patients, 12.6% (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4% (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14% of these samples showed increased pfmdr1 copy number; 100% (n = 21) had wild type allele of k13 gene in all the studied positions. DISCUSSION: These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area. PMID- 26670645 TI - Persistent mitral and tricuspid insufficiency. PMID- 26670646 TI - Clinical images of penetrating cardiac injury. PMID- 26670647 TI - Preantibiotic era revisited: Janeway's lesions and Osler's nodes. PMID- 26670648 TI - An undiagnosed double aortic arch hampers a coronary angiography in a patient with LIMA graft. PMID- 26670649 TI - Shot to the heart: retained left ventricular bullet. PMID- 26670650 TI - An impressive fungal infection of a permanent pacing system. PMID- 26670651 TI - An unusual cause of life-threatening right-sided heart failure: undifferentiated pleomorphic sarcoma in the right ventricular outflow tract. PMID- 26670652 TI - Massive vegetation in device-related endocarditis. PMID- 26670653 TI - Persistent post percutaneous coronary intervention angina investigated with invasive physiological testing. PMID- 26670654 TI - Evolution retraces its steps to advance. AB - Bacteria in a long-term evolution experiment evolved a new metabolic trait via two separate mutations with opposite effects. PMID- 26670655 TI - Are sickle cell anaemia and sickle cell trait predictive factors for periodontal disease? A cohort study. AB - BACKGROUND AND OBJECTIVE: Periodontal diseases are associated with bacterial challenge and the host immune response, and are also modulated by genetic factors. There is evidence that sickle cell anaemia (SCA) does not represent a risk factor for periodontal diseases. However, it is still unclear whether the heterozygous condition [sickle cell trait (SCT)] is associated with periodontal diseases. SCT is a genetic condition that can cause vaso-occlusive events, which may be associated with a propensity to bacterial infections. The aim of this study was to investigate the association of SCA and SCT with periodontal diseases by evaluating clinical and radiographic characteristics. MATERIAL AND METHODS: The sample (n = 369) was selected and divided into two groups: exposed groups [HbSS (SCA genotype) and HbAS (SCT genotype) = 246] and a nonexposed group (HbAA = 123). HbAA consisted of individuals without SCA and SCT. The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement. The percentage of alveolar bone loss was measured using a Schei ruler. Binomial and Poisson regressions were used to estimate correlations of interest (alpha = 0.05). RESULTS: None of the periodontal parameters was associated with SCA. SCT was associated with gingivitis (p = 0.041) and periodontitis (p = 0.002). Individuals with SCT had a lower plaque index (p = 0.044) but a higher calculus index (p = 0.003) and greater alveolar bone loss (p = 0.010) compared with subjects in the HbAA group. CONCLUSIONS: SCT can act as a predictor for establishment of periodontal diseases. There was no correlation between SCA and periodontal diseases. PMID- 26670656 TI - [Ketogenic diet as a therapeutic option in refractory epilepsy]. PMID- 26670657 TI - [Towards a maximum vaccination calendar: Assessment of a strategy]. PMID- 26670658 TI - [High incidence of type 1 diabetes in the immigrant population of Osona and Baix Camp]. AB - INTRODUCTION: It has been postulated that migration could act as a modifying factor in the incidence of Type 1 diabetes mellitus (T1DM), so the aim of this study is to determine if there are differences in the incidence of T1DM by origin. MATERIAL AND METHODS: Retrospective study of cases of T1DM onset in the population younger than 19 years old in Osona and Baix Camp between 2000 and 2012, using the medical histories of endocrinology units of the health centres and demographics from Catalonia Statistical Institute as sources. RESULTS: The child population in Osona and Baix Camp increased by 36.6%, with 18.9% in the local population, and 482% in the immigrant population, and most of this increase (90%) in the Maghreb immigrant group. A total of 118 diabetics onset were found, 66.9% in the local population, 32.2% Maghrebi population, and 0.9% in children from other countries, with a total incidence rate of 14.4 cases per 100,000 population/year (c/105p-y). The incidence is higher in the Maghrebi population compared to the local population, 37.1 vs 11.2 c/105p-y (P<.001), and in children under 5 years compared to the 5-18 years group, 18.9 vs 12.5 c/105p-y (P<.05), with no differences between sexes (P>.05). The relative risk is 3.1 for the Maghrebi population, and 1.5 for children under 5 years. CONCLUSIONS: The total incidence of T1DM remains stable, but is higher in the Maghrebi than in the local population, and in children under 5 years compared to 5-18 years group. These results opens a study field of which risk factors could be affecting this immigrant population in their destination countries. PMID- 26670659 TI - Unravelling Thiol's Role in Directing Asymmetric Growth of Au Nanorod-Au Nanoparticle Dimers. AB - Asymmetric nanocrystals have practical significance in nanotechnologies but present fundamental synthetic challenges. Thiol ligands have proven effective in breaking the symmetric growth of metallic nanocrystals but their exact roles in the synthesis remain elusive. Here, we synthesized an unprecedented Au nanorod-Au nanoparticle (AuNR-AuNP) dimer structure with the assistance of a thiol ligand. On the basis of our experimental observations, we unraveled for the first time that the thiol could cause an inhomogeneous distribution of surface strains on the seed crystals as well as a modulated reduction rate of metal precursors, which jointly induced the asymmetric growth of monometallic dimers. PMID- 26670660 TI - Prenatal Diagnosis of Antley-Bixler Syndrome and POR Deficiency. AB - BACKGROUND: Prenatal diagnosis of severe bone diseases is challenging and requires complete and precise analysis of fetal anomalies to guide genetic investigation and parental counselling. CASE REPORT: We report a rare case of Antley-Bixler syndrome prenatally diagnosed at 26 weeks' gestation by ultrasound and computed tomography in a 28-year-old woman with a history of early termination of pregnancy for "malposition of the inferior limbs". The prenatal ultrasound scan showed severe femoral bowing and frontal bossing. Taking into account the high probability of a recurrent severe skeletal disorder, a computed tomography (CT) scan was proposed. CT findings revealed bilateral femora deformation, craniosynostosis, severe midface hypoplasia, and radiohumeral synostosis. These anomalies strongly suggested Antley-Bixler syndrome. Sequencing of the POR gene in the fetus and the parents revealed compound heterozygous mutations in exon 9 and intron 7, both inherited from each parent, and this finding allowed genetic counseling. CONCLUSIONS: The first step in the proper prenatal diagnosis of fetal bone disorders is the precise analysis of ultrasonographic images. However, when a severe fetal inherited disorder is strongly suspected in late mid-trimester, CT may be discussed and usefully contribute to diagnosis and prognosis assessment. PMID- 26670662 TI - Comment on the Paper by van den Bosch et al. Entitled 'Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain': The Impact of Subtle Messaging. PMID- 26670661 TI - MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response. AB - The differentiation of fibroblasts into myofibroblasts mediates tissue wound healing and fibrotic remodelling, although the molecular programme underlying this process remains poorly understood. Here we perform a genome-wide screen for genes that control myofibroblast transformation, and identify the RNA-binding protein muscleblind-like1 (MBNL1). MBNL1 overexpression promotes transformation of fibroblasts into myofibroblasts, whereas loss of Mbnl1 abrogates transformation and impairs the fibrotic phase of wound healing in mouse models of myocardial infarction and dermal injury. Mechanistically, MBNL1 directly binds to and regulates a network of differentiation-specific and cytoskeletal/matrix assembly transcripts to promote myofibroblast differentiation. One of these transcripts is the nodal transcriptional regulator serum response factor (SRF), whereas another is calcineurin Abeta. CRISPR-Cas9-mediated gene-editing of the MBNL1-binding site within the Srf 3'UTR impairs myofibroblast differentiation, whereas in vivo deletion of Srf in fibroblasts impairs wound healing and fibrosis. These data establish a new RNA-dependent paradigm for myofibroblast formation through MBNL1. PMID- 26670663 TI - Eliciting Societal Preferences for Weighting QALYs for Burden of Illness and End of Life. AB - OBJECTIVES: . Recent proposals for value-based assessment, made by the National Institute of Health and Care Excellence (NICE) in the United Kingdom, recommended that burden of illness (BOI) should replace end of life (EOL) as a factor for consideration when deciding on new health technologies. This article reports on a study eliciting societal preferences for 1) BOI from a medical condition, defined as quality-adjusted life year (QALY) loss due to premature mortality and prospective morbidity, and 2) EOL, defined as expected life expectancy of less than 2 years and expected life expectancy gain from new treatment of 3 months or more. METHODS: . A discrete choice experiment survey was conducted with an online UK general population sample. Respondents chose whether they thought the health service should treat patient group A or B: life expectancy and health-related quality of life (HRQOL) with current treatment or life expectancy and HRQOL gains from new treatment, respectively. These attributes were used to derive BOI, QALY gain, and EOL. The respondents' choices were analyzed using conditional logistic regression with a range of specifications examined, including BOI or EOL, QALY gain and QALY gain squared, and robustness. QALY weights were estimated. RESULTS: . The sample of 3669 respondents was representative of the UK population for age and sex. QALY gain had a positive and significant coefficient across all models. QALY gain squared term was negative and significant across all models, indicating a diminishing marginal social value from QALY gains. When included, the BOI coefficient was generally small, positive, and significant, but this was not consistent across the different life expectancy variants. EOL was always positive and significant. CONCLUSIONS: . The social value of a QALY gain is not equal between recipients but depends on whether they are end of life, and it may depend on the prospective burden of illness. PMID- 26670664 TI - Maternal death reviews at Bugando hospital north-western Tanzania: a 2008-2012 retrospective analysis. AB - BACKGROUND: Unacceptably high levels of maternal deaths still occur in many sub Saharan countries and the health systems may not favour effective use of lessons from maternal death reviews to improve maternal survival. We report results from the analysis of data from maternal death reviews at Bugando Medical Centre north western Tanzania in the period 2008-2012 and highlight the process, challenges and how the analysis provided a better understanding of maternal deaths. METHODOLOGY: Retrospective analysis using maternal death review data and extraction of missing information from patients' files. Analysis was done in STATA statistical package into frequencies and means +/- SD and median with 95% CI for categorical and numerical data respectively. RESULTS: There were 80 deaths; mean age of the deceased 27.1 +/- 6.2 years and a median hospital stay of 11.0 days [95% CI 11.0-15.3]. Most deaths were from direct obstetric causes (90); 60% from eclampsia, severe pre-eclampsia, sepsis, abortion and anaesthetic complications. Information on ANC attendance was recorded in 36.2% of the forms and gestation age of the pregnancy resulting into the death in 23.8%. Sixty one deaths (76.3%) occurred after delivery. The mode of delivery, place of delivery and delivery assistant were recorded in 44 (72.1), 38 (62.3) and 23 (37.7%) respectively. CONCLUSION: Routine maternal death reviews in this setting do not involve comprehensive documentation of all relevant information, including actions taken to address some identified systemic weaknesses. Periodic analysis of available data may allow better understanding of vital information to improve the quality of maternity care. PMID- 26670665 TI - Effects of low dose of tibolone on steroid receptors and Bcl-2 on the postmenopausal endometrium. AB - OBJECTIVE: A prospective randomized controlled trial was conducted to evaluate the effect of low dose of tibolone on the histology, expression of estrogen (ER) and progesterone receptors (PR) and Bcl-2 protein, in endometrium of postmenopausal women. METHOD: Forty postmenopausal women consented to treatment and were allocated into two groups of 20 women: Group 1 (Control) without hormone replacement therapy (HRT); Group 2 (Tibolone) treatment at the dose of 1.25 mg/day of oral tibolone administered for a 24-week period. The effect on the endometrium was assessed by histology and the apoptosis marker Bcl-2. The immunoexpression of ER and PR were also measured. RESULTS: Tibolone group showed higher expression of ER, PR and Bcl-2 protein in glandular epithelium and stroma compared to control group. CONCLUSION: Tibolone in a daily dose of 1.25 mg during 24 weeks demonstrated endometrial action that resulted in low proliferation and was shown to lead to atrophic endometrium. It had favorable effects on the postmenopausal endometrium due to its higher immunoexpression of PR and Bcl-2 protein in endometrial glandular epithelium, thereby creating a balance between pro-apoptotic and anti-apoptotic actions. PMID- 26670666 TI - Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations. AB - BACKGROUND: Advanced penile squamous cell carcinoma (PSCC) is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs). MATERIALS AND METHODS: DNA was extracted from 40 MUm of formalin-fixed, paraffin-embedded sections in patients with advanced PSCC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 692* for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies on the market or under evaluation in mechanism-driven clinical trials. RESULTS: Twenty male patients with a median age of 60 years (range, 46-87 years) were assessed. Seventeen (85%) cases were stage IV and three cases (15%) were stage III. CGP revealed 109 GAs (5.45 per tumor), 44 of which were CRGAs (2.2 per tumor). At least one CRGA was detected in 19 (95%) cases, and the most common CRGAs were CDKN2A point mutations and homozygous deletion (40%), NOTCH1 point mutations and rearrangements (25%), PIK3CA point mutations and amplification (25%), EGFR amplification (20%), CCND1 amplification (20%), BRCA2 insertions/deletions (10%), RICTOR amplifications (10%), and FBXW7 point mutations (10%). CONCLUSION: CGP identified CRGAs in patients with advanced PSCC, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. IMPLICATIONS FOR PRACTICE: Few treatment options exist for patients with advanced penile squamous cell carcinoma (PSCC). Outcomes are dismal with platinum-based chemotherapy, with median survival estimated at 1 year or less across multiple series. Biological studies of patients with PSCC to date have principally focused on human papillomavirus status, but few studies have elucidated molecular drivers of the disease. To this end, comprehensive genomic profiling was performed in a cohort of 20 patients with advanced PSCC. Findings of frequent mutations in CDKN2A, NOTCH1, PIK3CA, and EGFR (all in excess of 20%) point to potential therapeutic avenues. Trials of targeted therapies directed toward these mutations should be explored. PMID- 26670668 TI - Liver injury and genetic polymorphisms in the cytochrome P450 and UDP glucuronosyltransferase genes. PMID- 26670667 TI - Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment. AB - BACKGROUND: Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified. METHODS: We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs. RESULTS: Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway. CONCLUSIONS: Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy. PMID- 26670669 TI - Erratum: Attenuation measurements show that the presence of a TachoSil surgical patch will not compromise target irradiation in intra-operative electron radiation therapy or high-dose-rate brachytherapy. AB - After publication of this study [1], the authors noticed that the funding was incorrectly acknowledged. The correct Acknowledgements section can be found below: "This work was partly funded by Fundacao para a Ciencia e Tecnologia (FCT), in the framework of the project PTDC/SAU-ENB/117631/2010, which is cofinanced by FEDER, through Programa Operacional Fatores de Competitividade - COMPETE of QREN (reference FCOMP-01-0124-FEDER-021141)." PMID- 26670670 TI - Harm: as indeterminate as 'best interests', but useful for triage. PMID- 26670671 TI - Should uterus transplants be publicly funded? AB - Since 2000, 11 human uterine transplantation procedures (UTx) have been performed across Europe and Asia. Five of these have, to date, resulted in pregnancy and four live births have now been recorded. The most significant obstacles to the availability of UTx are presently scientific and technical, relating to the safety and efficacy of the procedure itself. However, if and when such obstacles are overcome, the most likely barriers to its availability will be social and financial in nature, relating in particular to the ability and willingness of patients, insurers or the state to pay. Thus, publicly funded healthcare systems such as the UK's National Health Service (NHS) will eventually have to decide whether UTx should be funded. With this in mind, we seek to provide an answer to the question of whether there exist any compelling reasons for the state not to fund UTx. The paper proceeds as follows. It assumes, at least for the sake of argument, that UTx will become sufficiently safe and cost-effective to be a candidate for funding and then asks, given that, what objections to funding there might be. Three main arguments are considered and ultimately rejected as providing insufficient reason to withhold funding for UTx. The first two are broad in their scope and offer an opportunity to reflect on wider issues about funding for infertility treatment in general. The third is narrower in scope and could, in certain forms, apply to UTx but not other assisted reproductive technologies (ARTs). The first argument suggests that UTx should not be publicly funded because doing so would be inconsistent with governments' obligations to prevent climate change and environmental pollution. The second claims that UTx does not treat a disorder and is not medically necessary. Finally, the third asserts that funding for UTx should be denied because of the availability of alternatives such as adoption and surrogacy. PMID- 26670672 TI - Non-healing perianal ulcer in an immunocompetent patient as the presenting sign of a systemic disease. PMID- 26670673 TI - Current use of diverting stoma in anterior resection for cancer: population-based cohort study of total and partial mesorectal excision. AB - PURPOSE: A diverting stoma is commonly used to reduce the risk of anastomotic leakage when performing total mesorectal excision (TME) in anterior resection for rectal cancer. The purpose of this study was to evaluate the impact of fecal diversion in relation to partial mesorectal excision (PME). METHODS: A retrospective analysis was undertaken on a national cohort, originally created to study the impact of central arterial ligation on patients with increased cardiovascular risk. Some 741 patients operated with anterior resection for rectal cancer during the years 2007 through 2010 were followed up for 53 months. Multivariate logistic regression was used to evaluate the impact of diverting stoma on the risk of anastomotic leakage and permanent stoma, expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of anastomotic leakage was increased in TME surgery when not using a diverting stoma (OR 5.1; 95% CI 2.2-11.6), while the corresponding risk increase in PME patients was modest (OR 1.8; 95% CI 0.8-4.0). At study completion or death, 26 and 13% of TME and PME patients, respectively, had a permanent stoma. A diverting stoma was a statistically significant risk factor for a permanent stoma in PME patients (OR 4.7; 95% CI 2.5-9.0), while less important in TME patients (OR 1.8; 95% CI 0.6 5.5). CONCLUSION: The benefit of a diverting stoma concerning anastomotic leakage in this patient group seems doubtful. Moreover, the diverting stoma itself may contribute to the high rate of permanent stomas. PMID- 26670674 TI - Early complication detection after colorectal surgery (CONDOR): study protocol for a prospective clinical diagnostic study. AB - PURPOSE: Anastomotic leakage is one of the most feared complications following colorectal surgery with a high morbidity and mortality rate. Multiple risk factors have been identified, but leakage still occurs. Early detection is crucial in order to reduce morbidity and mortality. The aim of this study is to create a decision algorithm for early detection of anastomotic leakage. METHODS: All patients who undergo elective colorectal surgery for benign or malignant disease are enrolled in this multicenter study. The primary endpoint is the accuracy of the prediction of anastomotic leakage. The main study parameter is the occurrence of postoperative anastomotic leakage. Secondary study parameters are clinical (vital) parameters, additional laboratory or radiology examination, other complications, mortality, re-intervention, duration of hospital and intensive care stay, emergency room visits, readmission to the hospital and total costs. Daily physical examination and each step in clinical decision making will be evaluated prospectively in a standardized manner. The focus of the analysis will be on the added value of diagnostic tools, such as laboratory results and imaging studies, over physical examination by using logistic regression and decision tree analysis. CONCLUSION: This study aims to develop an optimal diagnostic algorithm that can act as a guideline for surgeons or surgical residents to early identify patients with anastomotic leakage after colorectal surgery. PMID- 26670675 TI - The microbiome of diabetic foot osteomyelitis. AB - The purpose of this investigation was to evaluate the diversity of bacteria in diabetic foot osteomyelitis using a 16S rRNA sequencing approach and to compare the results with conventional culture techniques. In this prospective observational study, we obtained 34 bone samples from patients admitted to our hospital with a moderate-severe diabetic foot infection. We analysed the distribution of the 16S rRNA gene sequences in the bone samples, using an Illumina MiSeq Personal Sequencer. We compared the genera that were detected with the cultured pathogens in the bone samples with conventional techniques. In the 23 samples that had positive results with both techniques, Staphylococcus, Corynebacterium, Streptococcus and Propionibacterium spp. were detected in 20, 18, 13 and 11 samples, respectively. Significantly more anaerobes were detected with 16S rRNA sequencing compared to conventional techniques (86.9 % vs. 23.1 %, p = 0.001) and more Gram-positive bacilli were present (78.3 % vs. 3.8 %, p < 0.001). Staphylococcus spp. were identified in all of the sequenced bone samples that were negative with conventional techniques. Mixed genera were present in 83.3 % (5 of 6) of the negative samples. Anaerobic and fastidious organisms may play a more significant role in osteomyelitis than previously reported. Further studies with larger populations are needed in order to fully understand the clinical importance of the microbial diversity of diabetic foot osteomyelitis. PMID- 26670676 TI - Diradical Character Tuning for the Third-Order Nonlinear Optical Properties of Quinoidal Oligothiophenes by Introducing Thiophene-S,S-dioxide Rings. AB - To create a design guideline for efficient third-order nonlinear optical (NLO) molecules, the chain-length (n) dependences of the diradical character y and the longitudinal second hyperpolarizability gamma of quinoidal oligothiophenes (QTs), from monomers to octamers, involving thiophene-S,S-dioxide rings are investigated by using the density functional theory method. It turns out that the diradical character of the modified QTs is reduced as compared to those of the pristine QTs. By introducing an appropriate number of oxidized rings into the QT framework, intermediate y values can be achieved even in the systems with large values of n, in which the pristine QTs are predicted to have pure diradical character. Such intermediate diradical oligomers are shown to exhibit enhanced gamma values as compared to the pristine QTs with the same value for n. From the calculation results, the introduction of the optimal number of thiophene-S,S dioxide rings is predicted to be an efficient chemical modification for optimizing the third-order NLO properties of open-shell QTs through tuning the diradical characters. PMID- 26670677 TI - Natural and experimental tests of trophic cascades: gray wolves and white-tailed deer in a Great Lakes forest. AB - Herbivores can be major drivers of environmental change, altering plant community structure and changing biodiversity through the amount and species of plants consumed. If natural predators can reduce herbivore numbers and/or alter herbivore foraging behavior, then predators may reduce herbivory on sensitive plants, and a trophic cascade will emerge. We have investigated whether gray wolves (Canis lupus) generate such trophic cascades by reducing white-tailed deer (Odocoileus virginianus) herbivory on saplings and rare forbs in a northern mesic forest (Land O' Lakes, WI). Our investigation used an experimental system of deer exclosures in areas of high and low wolf use that allowed us to examine the role that wolf predation may play in reducing deer herbivory through direct reduction in deer numbers or indirectly through changing deer behavior. We found that in areas of high wolf use, deer were 62 % less dense, visit duration was reduced by 82 %, and percentage of time spent foraging was reduced by 43 %; in addition, the proportion of saplings browsed was nearly sevenfold less. Average maple (Acer spp.) sapling height and forb species richness increased 137 and 117 % in areas of high versus low wolf use, respectively. The results of the exclosure experiments revealed that the negative impacts of deer on sapling growth and forb species richness became negligible in high wolf use areas. We conclude that wolves are likely generating trophic cascades which benefit maples and rare forbs through trait-mediated effects on deer herbivory, not through direct predation kills. PMID- 26670678 TI - Endoluminal therapies for Barrett's esophagus. AB - This paper reviews currently available endoluminal therapies for Barrett's esophagus, which may be integrated into the care of obese and bariatric surgery patients. PMID- 26670679 TI - Comparison of Preoperative Diets Before Bariatric Surgery: a Randomized, Single Blinded, Non-inferiority Trial. AB - OBJECTIVE: In order to increase weight loss and minimize complications, a preoperative diet before bariatric has been advocated. However, some diets are poorly tolerated by patients and this can lead to low compliance and too little weight loss. In this study, we aim to compare two preoperative diets in order to find the most suitable for this patient population. METHODS: Comparison of preoperative diets before bariatric surgery with a randomized non-inferiority trial in order to compare the standard very low calorie diet (VLCD) by protein shakes (Prodimed) with a standard diet using ordinary products. The primary outcome parameter was preoperative weight loss. Secondary outcome parameters were operation time, difficulty of surgery, short-term complications, short-term weight loss and compliance, tolerance, and acceptance of the diets. RESULTS: Two hundred twelve patients suitable for gastric bypass surgery were included and randomized. The Prodimed group contained 105 patients, the standard diet group 107 patients. Preoperative weight loss and 4 weeks after the procedure were not significantly different between the two diet groups. Operation time, difficulty of surgery, short-term complications, and short-term weight loss were also comparable without significant differences between the diet groups. However, most of the parameters measuring patients' compliance, tolerance, and acceptance of the diets were significantly better in the standard diet group as compared to the patients in the Prodimed group. CONCLUSION: Protein shakes and standard diets are capable of achieving good and comparable results on preoperative weight loss before bariatric surgery. However, patients' compliance, tolerance, and acceptance were all significantly better after a standard diet. We recommend giving patients a choice in preoperative diets in order to achieve the best possible weight loss and results. PMID- 26670680 TI - Visualization of biosensors using enhanced surface plasmon resonances in capped silver nanostructures. AB - We propose a method and optical design for direct visualization of label-free detection. The system, similar to a tiny spectral analyzer, is composed of a nanostructure-based surface plasmon resonance chip, linear polarizer and 532 nm laser light source. The full-width-at-half-maximum bandwidths of the enhanced surface plasmon resonances are about 5 nm. The distribution of the transmitted light from these arrays comprises a spectral image on the chip. The qualitative and quantitative analyses of the analyte can be conducted by observing the spot shift on the chip. We tested the sensing capability of the chip. The detectable surface mass density with the naked eye is about 0.476 MUg cm(-2). In addition, antigen-antibody interaction experiments are conducted to verify the surface binding measurements. A monolayer protein attached on the chip can be directly observed and the concentration levels of the analyte can be estimated with the naked eye. Such plasmonic biochips can benefit sensing applications in point-of care diagnostics. PMID- 26670682 TI - The role of orthodontics in the regeneration of the degenerated dentition. AB - The demand for regeneration of a degenerated dentition has been increasing as a result of the development of societies, where the life expectancy is increasing and fighting age-related changes is in focus. Whereas removable dentures were acceptable and considered a norm earlier, patients do, to an increasing degree,demand fixed prosthetics; consequently, the development of implants has had an important impact. The balance in the chewing organ will change with time, due to age-related changes within the bone and the loss of teeth due to caries or periodontal disease, and malocclusions may develop or aggravate. The re establishment of an aesthetical and functional satisfactory solution cannot be reached by replacing teeth by fixed prosthodontics and implants. The aim of this update was threefold: firstly, to demonstrate that age-related changes, often unnoticed by both the patient and the general dentist, can lead to degeneration of the dentition; secondly, to explain how an interdisciplinary approach can make regeneration of even severe degeneration possible; and finally, to show the importance of the general dentist in the maintenance of the obtained results. Treatments should not aim for short-term results but focus on maintainable results. PMID- 26670681 TI - Collembola at three alpine subarctic sites resistant to twenty years of experimental warming. AB - This study examined the effects of micro-scale, site and 19 and 21 years of experimental warming on Collembola in three contrasting alpine subarctic plant communities (poor heath, rich meadow, wet meadow). Unexpectedly, experimental long-term warming had no significant effect on species richness, effective number of species, total abundance or abundance of any Collembola species. There were micro-scale effects on species richness, total abundance, and abundance of 10 of 35 species identified. Site had significant effect on effective number of species, and abundance of six species, with abundance patterns differing between sites. Site and long-term warming gave non-significant trends in species richness. The highest species richness was observed in poor heath, but mean species richness tended to be highest in rich meadow and lowest in wet meadow. Warming showed a tendency for a negative impact on species richness. This long term warming experiment across three contrasting sites revealed that Collembola is capable of high resistance to climate change. We demonstrated that micro-scale and site effects are the main controlling factors for Collembola abundance in high alpine subarctic environments. Thus local heterogeneity is likely important for soil fauna composition and may play a crucial role in buffering Collembola against future climate change. PMID- 26670683 TI - Reexamining Oxidation States during the Synthesis of 2-Rhodaoxetanes from Olefins. AB - Herein, we report experimental, spectroscopic, and computational data that indicate that a rhodium ethylene complex, formally described as rhodium(I) and which forms a 2-rhoda(III) oxetane following reaction with H2O2, is more accurately described as a rhodium(III) metallacyclopropane. X-ray absorption spectroscopy clearly demonstrates a change in the oxidation state at rhodium following ligand coordination with tris(2-pyridylmethyl)amine. Both NMR and density functional theory studies suggest a high energy barrier to rotation of the coordinated ethylene, which is attributed to large geometric and electronic reorganization resulting from the loss of pi-back-bonding. These results imply that the role of H2O2 in the formation of 2-rhoda(III) oxetanes is to oxidize the C2H4 fragment rather than the metal center, as has been previously suggested. PMID- 26670684 TI - Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit. AB - BACKGROUND: The aim of this study was to report the emergence of linezolid resistant coagulase-negative staphylococci (CoNS) in an intensive care unit. METHODS: An observational study was conducted in critically ill patients with colonization or infection by linezolid-resistant CoNS between January 2010 and December 2014. We analyzed the epidemiological and clinical features, and the mechanism of resistance to linezolid. We also evaluated the association between the incidence of linezolid-resistant CoNS strains and the consumption of linezolid in the study period. RESULTS: During the study period 49 patients had a linezolid-resistant CoNS strain isolated from clinical samples (blood in 42 cases, urine in 6, peritoneal fluid in 1). Molecular study showed a combination of mechanisms of resistance. Most patients were critically ill (APACHE II score = 21.9 +/- 8.3) and nearly all had undergone surgery and invasive procedures, and had prior exposure to antibiotics. Linezolid-resistant CoNS were considered to be contaminants in 42 patients and associated with infection in 7 patients, comprising bacteremia and septic shock in most of them. They were successfully treated with glycopeptides or daptomycin. A modest significant correlation was observed between the decrease in linezolid consumption and the lower incidence of resistant isolates. CONCLUSIONS: Linezolid-resistant CoNS had emerged in critically ill patients with severe underlying diseases and prior antibiotic exposure. Most isolates represented colonization; however, linezolid-resistant CoNS can produce serious infections in critically ill patients. Glycopeptides and daptomycin seem to provide useful alternatives for therapy of these infections. A relationship was found between linezolid consumption and the incidence of linezolid-resistant CoNS strains. PMID- 26670685 TI - Myles Jackson, The Genealogy of a Gene : MIT Press, Cambridge, MA, 2015. PMID- 26670686 TI - Models of biobanks and implications for reproductive health innovation. AB - Biobanks are designed with particular purposes in mind. These purposes are reflected in the governance frameworks that define the conditions for participation and access by researchers. In this paper, I analyse two different models: the commercially aligned deCODE biobank and the 'public good' framework of UK Biobank. These diametric models have both featured 'the public interest' as pivotal to their achievements. However, if properly understood, the public interest rhetoric of deCODE actually conflicts with any professed community interest. The reasons why are explained, and the effects this has on conditions for participation are critiqued, before reflecting on how each model might have an impact on reproductive health research. PMID- 26670687 TI - A Fluorescent Hypochlorite Probe Built on 1,10-Phenanthroline Scaffold and its Ion Recognition Features. AB - In this study, the synthesis of 7-((Hydroxyimino)methyl)-1,10-phenanthroline-4 carbaldehyde oxime (1) in two steps starting from 4,7-dimethyl-1,10 phenanthroline (2) is reported. It is found that compound 1 can be used as a fluorogenic probe for the detection of hypochlorite ion in aqueous solution. NMR and mass spectral analysis indicate that probe 1 undergoes a chemical transformation through its oxime units upon treatment with hypochlorite, which results in a remarkable enhancement of the emission intensity. Also, metal ion recognition properties of probe 1 is investigated. It is noted that compound 1 is responsive to Zn(2+), Cd(2+), Ni(2+) and Cu(2+) metal ions, which reduced the emission intensity under identical conditions. Graphical Abstract The design, synthesis and properties of a new fluorescent hypochlorite probe is described. It is found that probe 1 immediately undergoes an oxidation reaction with NaClO through its oxime units in 0.1 M Na2CO3-NaHCO3 buffer containing DMF (pH = 9.0, 30:1 v/v) at room temperature, which resulted in a remarkable enhancement of the emission intensity. It is noteworthy that this novel probe 1 is highly selective to hypochlorite ion when compared to some other ROS and anions. On the other hand, probe 1 also induces turn-off fluorogenic responses to metal ions such as Zn(2+), Cd(2+), Ni(2+) and Cu(2+) ions under identical conditions. PMID- 26670688 TI - Spectroscopy and Molecular Modeling Study on the Interaction Between Mycophenolate Mofetil and Pepsin. AB - Mycophenolate mofetil (MMF) is an immunosuppressant used in clinical practice to limit the rejection of transplanted organs. MMF is absorbed and metabolized by the gastrointestinal tract and converted to mycophenolic acid by esterases in the plasma, liver, and kidney. Mycophenolic acid is the resulting active metabolite. The interaction of MMF with pepsin may affect the transfer and distribution of MMF. Given this effect, the present study investigated the interaction behavior between pepsin with MMF using docking simulation and spectroscopy method at different temperatures. The results of spectroscopy revealed that MMF has strong ability to quench the fluorescence of pepsin. The results also show that the acting force for binding was composed of hydrophobic forces. The three dimensional fluorescence spectra and synchronous spectroscopy employed to determine the conformation showed that the binding of MMF with pepsin could induce MMF conformation and microenvironment changes. Furthermore, the molecular interaction distance and energy-transfer efficiency between pepsin and MMF were determined based on the Forster non-radiative energy-transfer mechanism. Docking simulation showed that MMF entered the hydrophobic cavity of pepsin, and a hydrogen bond was formed between the oxygen atoms of the carbanyl group of MMF and hydrogen atoms of tyrosine 189 of pepsin. PMID- 26670689 TI - Complexation of Donor-Acceptor Substituted Aza-Crowns with Alkali and Alkaline Earth Metal Cations. Charge Transfer and Recoordination in Excited State. AB - Complexation between two aza-15-crown-5 ethers bearing electron donor and acceptor fragments and alkali and alkaline earth perchlorates has been studied using absorption, steady-state fluorescence and femtosecond transient absorption spectroscopy. The spectral-luminescent parameters, the stability and dissociation constants of the complexes were calculated. The intramolecular charge transfer reaction takes place both in the excited state of the crowns and their complexes 1:1; the latter is subjected to photorecoordination resulting in a weakening or a complete disruption of coordination bond between nitrogen atom and metal cation, disposed within a cavity of the crown. The compounds investigated can be viewed as novel optical molecular sensors for alkali and alkaline-earth metal cations. The photoejection of a metal cation into the bulk was not observed. PMID- 26670690 TI - Pediatric laminopathies: Whole-body magnetic resonance imaging fingerprint and comparison with Sepn1 myopathy. AB - INTRODUCTION: We sought to define the whole-body MRI (WB-MRI) fingerprint of muscle involvement in pediatric LMNA-related dystrophy (LMNA-RD) and to compare it with SEPN1-related myopathy (SEPN1-RM). METHODS: Signal abnormality and atrophy in 109 muscles were scored by semiquantitative scales in 8 children with LMNA-RD and represented by heatmaps. These features were compared with those from 9 SEPN1-RM patients by random forests. RESULTS: LMNA-RD showed predominant signal abnormalities in erector spinae, serratus anterior, subscapularis, gluteus medius and minimus, vastii, adductor magnus and longus, semimembranosus, medial gastrocnemius, and soleus muscles. Psoas, sternocleidomastoid, gracilis, and sartorius muscles often had normal signal but showed atrophy. Cranial, flexor digitorum longus, and tibialis posterior muscles were spared. According to random forests, atrophied semimembranosus in SEPN1-RM was the most relevant feature to distinguish these patients from LMNA-RD. CONCLUSIONS: A selective pattern in WB MRI for pediatric LMNA-RD exists and can be differentiated from SEPN1-RM by machine learning. Muscle Nerve 54: 192-202, 2016. PMID- 26670692 TI - Determination of Oxalate Content in Herbal Remedies and Dietary Supplements Based on Plant Extracts. AB - Lifestyle, especially diet, is a prominent risk factor that affects the formation of calcium oxalate stones. Urinary oxalate excretion is directly related to the amount of oral intake and intestinal absorption rate of oxalate. This work evaluated the possibility of increasing oxalate ingestion, which could lead to secondary hyperoxaluria, associated with the intake of herbal remedies and dietary supplements containing plant extracts. A wide variety of 17 commercially available drugs and dietary supplements were analyzed using ion chromatography. The results showed remarkable differences in oxalate contents of the extracts. Total oxalate concentrations ranged from 0.03 to 2.2 mg/g in solid samples and from 0.005 to 0.073 mg/mL in liquid samples. The selected herbal remedies and dietary supplements containing plant extracts represent only a low risk for calcium oxalate stone formers, if the recommended daily dose is not exceeded. PMID- 26670691 TI - Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a stress-sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well-studied in IBS. We performed a pilot study investigating genome wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits. METHODS: Twenty-seven IBS patients (59% women; 10 IBS-diarrhea, 8 IBS constipation, 9 IBS-mixed) and 23 age- and sex-matched HCs were examined. DNA methylation from peripheral blood mononuclear cells (PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non-GI symptoms were measured using validated questionnaires. Associations were tested using non-parametric methods. KEY RESULTS: Genome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions (DMPs) (mean difference >=10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)-Spondin (SSPO), glutathione-S-transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing. Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05). CONCLUSIONS & INFERENCES: This study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies. PMID- 26670693 TI - Photocleavable linker for the patterning of bioactive molecules. AB - Herein, we report the use of a versatile photocleavable nitrobenzyl linker to micropattern a wide variety of bioactive molecules and photorelease them on demand. On one end, the linker has an NHS group that can be coupled with any amine, such as peptides, proteins or amine-linkers, and on the other end an alkyne for convenient attachment to materials with an azide functional group. This linker was conjugated with NTA-amine or the cell adhesion peptide cRGD to enable straightforward patterning of His6-tagged proteins or cells, respectively, on PEGylated glass surfaces. This approach provides a practical way to control the presentation of a wide variety of bioactive molecules with high spatial and temporal resolution. The extent of photocleavage can also be controlled to tune the biomolecule density and degree of cell attachment to the surface. PMID- 26670694 TI - Erythropoietin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy. AB - Experimental studies targeting traumatic brain injury (TBI) have reported that erythropoietin (EPO) is an endogenous neuroprotectant in multiple models. In addition to its neuroprotective effects, it has also been shown to enhance reparative processes including angiogenesis and neurogenesis. Based on compelling pre-clinical data, EPO was tested by the Operation Brain Trauma Therapy (OBTT) consortium to evaluate therapeutic potential in multiple TBI models along with biomarker assessments. Based on the pre-clinical TBI literature, two doses of EPO (5000 and 10,000 IU/kg) were tested given at 15 min after moderate fluid percussion brain injury (FPI), controlled cortical impact (CCI), or penetrating ballistic-like brain injury (PBBI) with subsequent behavioral, histopathological, and biomarker outcome assessments. There was a significant benefit on beam walk with the 5000 IU dose in CCI, but no benefit on any other motor task across models in OBTT. Also, no benefit of EPO treatment across the three TBI models was noted using the Morris water maze to assess cognitive deficits. Lesion volume analysis showed no treatment effects after either FPI or CCI; however, with the 5000 IU/kg dose of EPO, a paradoxical increase in lesion volume and percent hemispheric tissue loss was seen after PBBI. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No treatment effects were seen on biomarker levels after FPI, whereas treatment at either dose exacerbated the increase in GFAP at 24 h in PBBI but attenuated 24-4 h delta UCH L1 levels at high dose in CCI. Our data indicate a surprising lack of efficacy of EPO across three established TBI models in terms of behavioral, histopathological, and biomarker assessments. Although we cannot rule out the possibility that other doses or more prolonged treatment could show different effects, the lack of efficacy of EPO reduced enthusiasm for its further investigation in OBTT. PMID- 26670696 TI - History and future of human cadaver preservation for surgical training: from formalin to saturated salt solution method. AB - Traditionally, surgical training meant on-the-job training with live patients in an operating room. However, due to advancing surgical techniques, such as minimally invasive surgery, and increasing safety demands during procedures, human cadavers have been used for surgical training. When considering the use of human cadavers for surgical training, one of the most important factors is their preservation. In this review, we summarize four preservation methods: fresh frozen cadaver, formalin, Thiel's, and saturated salt solution methods. Fresh frozen cadaver is currently the model that is closest to reality, but it also presents myriad problems, including the requirement of freezers for storage, limited work time because of rapid putrefaction, and risk of infection. Formalin is still used ubiquitously due to its low cost and wide availability, but it is not ideal because formaldehyde has an adverse health effect and formalin-embalmed cadavers do not exhibit many of the qualities of living organs. Thiel's method results in soft and flexible cadavers with almost natural colors, and Thiel embalmed cadavers have been appraised widely in various medical disciplines. However, Thiel's method is relatively expensive and technically complicated. In addition, Thiel-embalmed cadavers have a limited dissection time. The saturated salt solution method is simple, carries a low risk of infection, and is relatively low cost. Although more research is needed, this method seems to be sufficiently useful for surgical training and has noteworthy features that expand the capability of clinical training. The saturated salt solution method will contribute to a wider use of cadavers for surgical training. PMID- 26670697 TI - Dynamics of colloids confined in microcylinders. AB - We studied both global and local effects of cylindrical confinement on the diffusive behavior of hard sphere (HS) colloids. Using confocal scanning laser microscopy (CSLM) and particle tracking, we measured the mean squared displacement (MSD) of 1 micron sized silica particles in water-glycerol. This combination of fluid and setup allowed us to measure MSDs in a 4-dimensional parameter space, defined by the HS volume fraction (Phi: 0.05-0.39), cylinder radius (R: 2.5-20 micron), distance to the wall (z) and lagtime (tau: 0.03-60 s). MSDs for the entire cylinder confirm earlier findings that both narrowing the cylinder and populating it cause a slower dynamics. Additionally a decrease in R was found to cause a stronger ordering of the fluid. The effect of confinement on dynamics was further examined as a function of (z) location. For the largest cylinder (with minor curvature), we found that the strong decrease in MSD near the wall, becomes much less pronounced for higher Phi. Analyzing the radial (r) and azimuthal (theta) components, we found pronounced differences in the z dependence that were 'hidden' in the total MSD. Near the wall, the r-MSD shows a much steeper z-dependence while at larger z, it shows a remarkable anti correlation with the (peaked) density n(z). Also the dependence of the r-MSD on lagtime correlates with n(z): diffusive in between layers, but subdiffusive inside layers. These observations bring earlier findings together, while also shedding new light on the diffusive dynamics of concentrated colloids in narrow capillaries. PMID- 26670695 TI - Cervical cancer control in Latin America: A call to action. AB - Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology-based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources. PMID- 26670698 TI - Corrigendum: Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression. PMID- 26670701 TI - Detection of Plasmon Coupling between Silver Nanowires Based on Hyperspectral Darkfield and SERS Imaging and Supported by DDA Theoretical Calculations. AB - We report the unprecedented observation of plasmon coupling between silver nanowires, showing how the surface-enhanced Raman scattering depends upon this interaction and how the spectrum can be shaped by the hot spot. Such observations were accomplished by Raman spectroscopy mapping of silver nanowires modified with rhodamine. The local spectra on the hot spots were measured by darkfield hyperspectral microscopy, a powerful but uncommonly used technique that is capable of determining the location, structure, and spectra of the hot spots. The result obtained by the simulation of two parallel nanowires based on the discrete dipole approximation (DDA) method was in excellent agreement with the results obtained experimentally. PMID- 26670700 TI - Hierarchical Novelty-Familiarity Representation in the Visual System by Modular Predictive Coding. AB - Predictive coding has been previously introduced as a hierarchical coding framework for the visual system. At each level, activity predicted by the higher level is dynamically subtracted from the input, while the difference in activity continuously propagates further. Here we introduce modular predictive coding as a feedforward hierarchy of prediction modules without back-projections from higher to lower levels. Within each level, recurrent dynamics optimally segregates the input into novelty and familiarity components. Although the anatomical feedforward connectivity passes through the novelty-representing neurons, it is nevertheless the familiarity information which is propagated to higher levels. This modularity results in a twofold advantage compared to the original predictive coding scheme: the familiarity-novelty representation forms quickly, and at each level the full representational power is exploited for an optimized readout. As we show, natural images are successfully compressed and can be reconstructed by the familiarity neurons at each level. Missing information on different spatial scales is identified by novelty neurons and complements the familiarity representation. Furthermore, by virtue of the recurrent connectivity within each level, non-classical receptive field properties still emerge. Hence, modular predictive coding is a biologically realistic metaphor for the visual system that dynamically extracts novelty at various scales while propagating the familiarity information. PMID- 26670702 TI - Feeding the Need: Cardiovascular Science in "Heart Lung and Circulation". PMID- 26670699 TI - Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2. AB - Herpes simplex virus 2 (HSV-2) 0DeltaNLS is a live HSV-2 ICP0- mutant vaccine strain that is profoundly attenuated in vivo due to its interferon hypersensitivity. Recipients of the HSV-2 0DeltaNLS vaccine are resistant to high dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0DeltaNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0DeltaNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV 2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient MUMT mice. Vaccination with live HSV-2 0DeltaNLS induced equivalent CD8+ T cell responses in wild-type and MUMT mice. Vaccinated MUMT mice shed ~40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell+) mice, and most vaccinated MUMT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0DeltaNLS-vaccinated MUMT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2. PMID- 26670703 TI - Gray Ta2O5 Nanowires with Greatly Enhanced Photocatalytic Performance. AB - Black TiO2, with enhanced solar absorption and photocatalytic activity, has gained extensive attention, inspiring us to investigate the reduction of other wide-bandgap semiconductors for improved performance. Herein, we report the preparation of gray Ta2O5 nanowires with disordered shells and abundant defects via aluminum reduction. Its water decontamination is 2.5 times faster and hydrogen production is 2.3-fold higher over pristine Ta2O5. The reduced Ta2O5 also delivers significantly enhanced photoelectrochemical performance compared with the pristine Ta2O5 nanowires, including much higher carrier concentration, easier electron-hole separation and 11 times larger photocurrent. Our results demonstrate that Ta2O5 will have great potentials in photocatalysis and solar energy utilization after proper modification. PMID- 26670704 TI - Design, synthesis and in vitro evaluation of d-glucose-based cationic glycolipids for gene delivery. AB - A cationic lipid consists of a hydrophilic headgroup, backbone and hydrophobic tails which have an immense influence on the transfection efficiency of the lipid. In this paper, two novel series of cationic cyclic glycolipids with a quaternary ammonium headgroup and different-length hydrophobic tails (dodecyl, tetradecyl, hexadecyl) have been designed and synthesized for gene delivery. One contains lipids 1-3 with two hydrophobic alkyl chains linked to the glucose ring directly via an ether link. The other contains lipids 4-6 with two hydrophobic chains on the positively charged nitrogen atoms. All of the lipids were characterized for their ability to bind to DNA, size, zeta-potential, and toxicity. Atomic force microscopy showed that the lipids and DNA-lipid complexes were sphere-like forms. The lipids were used to transfer enhanced green fluorescent protein (EGFP-C3) to HEK293 cells without a helper lipid, the results indicated that lipids 4-6 have better transfection efficiency, in particular lipids 5-6 have similar or better efficiency, compared with the commercial transfection reagent lipofectamine 2000. PMID- 26670705 TI - Submicrometer-Sized Thermometer Particles Exploiting Selective Nucleic Acid Stability. AB - Encapsulated nucleic acid selective damage quantification by real-time polymerase chain reaction is used as sensing mechanism to build a novel class of submicrometer size thermometer. Thanks to the high thermal and chemical stability, and the capability of storing the read accumulated thermal history, the sensor overcomes some of current limitations in small scale thermometry. PMID- 26670706 TI - Inhibitory effects of some phenolic compounds on the activities of carbonic anhydrase: from in vivo to ex vivo. AB - Carbonic anhydrase (CA) inhibitors have been used for more than 60 years for therapeutic purposes in many diseases table such as in medications against antiglaucoma and as diuretics. Phenolic compounds are a new class of CA inhibitor. In our study, we tested the effects of arachidonoyl dopamine, 2,4,6 trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid on esterase and the CO2-hydratase activities of CA I and II isozymes purified from in vivo to ex vivo. The Ki values of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid were 203.80, 1170.00 and 910.00 MUM, respectively for hCA I and 75.25, 354.00 and 1510.00 MUM, respectively for hCA II. Additionally, IC50 values from in vivo studies were found to be in the range of 173.25-1360.0 MUM for CA I and II, respectively, using CO2-hydratase activity methods. These results demonstrated that phenolic compounds used in in vivo studies could be used in different biomedical applications to inhibit approximately 30% of the CO2-hydratase activity of the total CA enzyme of rat erythrocytes. PMID- 26670707 TI - Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis. AB - BACKGROUND: Very little is known about the phenotypic expression of schizotypal traits in individuals with 22q11.2 deletion syndrome (22q11DS). The main purpose was to analyse the factorial structure, internal consistency and temporal stability of schizotypal traits, as well as their associations with prodromal states and clinical psychotic symptoms in adolescents with 22q11DS. METHOD: The sample comprised 61 adolescents with 22q11DS (mean = 14.95 years, s.d. = 2.13; n = 24 at follow-up). An age-matched comparison group (n = 61, mean = 15.44 years, s.d. = 1.76) was also included. The Schizotypal Personality Questionnaire (SPQ), the Structured Interview for Prodromal Syndromes, the Positive and Negative Syndrome Scale, and the Brief Psychiatric Rating Scale were used. RESULTS: Adolescents with 22q11DS scored higher than the control group on the interpersonal dimension and suspiciousness subscale of the SPQ. The analysis of the internal structure of the SPQ in the sample of 22q11DS participants yielded a three-component solution (cognitive-perceptual, interpersonal, and disorganized). In addition, internal consistency coefficients ranged between 0.63 and 0.91. The schizotypal traits were highly stable across a 3.6-year interval, and ranged from 0.50 to 0.63. Self-reported schizotypal traits correlated with interview-based ratings of prodromal states and psychotic symptoms. CONCLUSIONS: These results indicate that the SPQ may be a valid tool to assess schizotypal traits in adolescents with 22q11DS. The identification of a reliable self-report instrument for use in individuals with learning disabilities and at genetic high risk for psychosis could be useful in clinical and research settings. Assessment of schizotypal traits may be used as a distal risk marker and in a close-in strategy in high-risk genetic samples to enhance the possibility of early detection of psychosis. PMID- 26670708 TI - Microsolvation of methylmercury: structures, energies, bonding and NMR constants ((199)Hg, (13)C and (17)O). AB - Hartree-Fock (HF) and second order perturbation theory (MP2) calculations within the scalar and full relativistic frames were carried out in order to determine the equilibrium geometries and interaction energies between cationic methylmercury (CH3Hg(+)) and up to three water molecules. A total of nine structures were obtained. Bonding properties were analyzed using the Quantum Theory of Atoms In Molecules (QTAIM). The analyses of the topology of electron densities reveal that all structures exhibit a partially covalent HgO interaction between methylmercury and one water molecule. Consideration of additional water molecules suggests that they solvate the (CH3HgOH2)(+) unit. Nuclear magnetic shielding constants sigma((199)Hg), sigma((13)C) and sigma((17)O), as well as indirect spin-spin coupling constants J((199)Hg-(13)C), J((199)Hg-(17)O) and J((13)C-(17)O), were calculated for each one of the geometries. Thermodynamic stability and the values of NMR constants correlate with the ability of the system to directly coordinate oxygen atoms of water molecules to the mercury atom in methylmercury and with the formation of hydrogen bonds among solvating water molecules. Relativistic effects account for 11% on sigma((13)C) and 14% on sigma((17)O), which is due to the presence of Hg (heavy atom on light atom, HALA effect), while the relativistic effects on sigma((199)Hg) are close to 50% (heavy atom on heavy atom itself, HAHA effect). J-coupling constants are highly influenced by relativity when mercury is involved as in J((199)Hg-(13)C) and J((199)Hg-(17)O). On the other hand, our results show that the values of NMR constants for carbon and oxygen, atoms which are connected through mercury (C HgO), are highly correlated and are greatly influenced by the presence of water molecules. Water molecules introduce additional electronic effects to the relativistic effects due to the mercury atom. PMID- 26670709 TI - Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis? AB - Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48 29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFbeta-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFbeta-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC. PMID- 26670711 TI - Retraction of Diagnostic Performance of Serum Macrophage Inhibitory Cytokine 1 in Pancreatic Cancer: A Meta-Analysis and Meta-Regression Analysis (DOI: 10.1089/dna.2013.2237). PMID- 26670710 TI - Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents. AB - OBJECTIVES: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. METHODS: We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. RESULTS: Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. CONCLUSIONS: Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents. PMID- 26670712 TI - Retraction of Relationships Between p16 Gene Promoter Methylation and Clinicopathologic Features of Colorectal Cancer: A Meta-Analysis of 27 Cohort Studies (DOI: 10.1089/dna.2013.2253). PMID- 26670713 TI - Confirmation of MRI anatomical measurements as endophenotypic markers for bipolar disorder in a new sample from the NIMH Genetics of Bipolar Disorder in Latino Populations study. AB - The main objective of this study is to establish potential neuromorphometric differences which might act as markers of genetic risk for bipolar disorder and therefore serve as endophenotypes for discovery of genes that contribute to bipolar disorder. Magnetic resonance imaging (MRI) was used to assess structural brain volumes of 49 subjects. Volumetric analyses were first performed to test possible differences in the volume of brain structures between subjects with bipolar disorder type I (BPI) and control subjects in a new sample, based on regions previously reported in the literature as being either increased or decreased in size in bipolar patients. Subsequently, for those brain regions showing statistical difference between subjects with BPI and control subjects in our new sample, we tested whether unaffected first degree relatives (UFRs) of the BPI subjects also showed similar differences compared with controls. Four specific regions (right prefrontal, right middle prefrontal, right globus pallidus and left globus pallidus) met criteria for being possible endophenotypes for BPI in this sample. PMID- 26670715 TI - Association of health insurance with outcomes in adults ages 18 to 64 years with melanoma in the United States. AB - BACKGROUND: Studies evaluating insurance status and melanoma outcomes are limited. OBJECTIVE: We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma. METHODS: This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database. RESULTS: Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001). LIMITATIONS: This was a retrospective study. CONCLUSION: Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes. PMID- 26670714 TI - Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach. AB - BACKGROUND: Squamous cell carcinoma in situ (SCCis) has been reported to involve the hair follicle epithelium. Deep follicular invasion is often cited as a cause of treatment failure. OBJECTIVE: We sought to define the frequency and the depth of hair follicle invasion by SCCis. METHODS: The study included both a retrospective review of intraoperative pathology specimens from 42 SCCis cases treated with Mohs micrographic surgery and a prospective evaluation of serially sectioned SCCis tissue from 12 additional patients. Pathology specimens were analyzed for follicular invasion of SCCis. RESULTS: SCCis invasion of the superficial hair follicle infundibulum was observed in 61.3% to 87.5% of cases in the 2 cohorts, whereas invasion of the isthmus and lower follicle was observed in only 8.3% to 12.5% of cases. In most tumors the depth of follicular invasion was comparable with the thickness of the surrounding epidermis. The maximum observed depth of follicular invasion was 0.82 mm. LIMITATIONS: The study was performed on a limited number of cases referred for surgery at a single institution. CONCLUSIONS: Although SCCis invasion of the upper hair follicle infundibulum is common, deep invasion below the level of the surrounding epidermis is rare. This may have implications for optimal therapy of this condition. PMID- 26670716 TI - Dermoscopy of Zoon's plasma cell balanitis. PMID- 26670717 TI - To the Editor. PMID- 26670719 TI - Delegation: a solution to the workload problem? Observations and interviews with community pharmacists in England. AB - OBJECTIVE: This study aims to describe how pharmacists utilise and perceive delegation in the community setting. METHOD: Non-participant observations and semi-structured interviews with a convenience sample of community pharmacists working in Kent between July and October 2011. Content analysis was undertaken to determine key themes and the point of theme saturation informed sample size. Findings from observations were also compared against those from interviews. KEY FINDINGS: Observations and interviews were undertaken with 11 pharmacists. Observations showed that delegation occurred in four different forms: assumed, active, partial and reverse. It was also employed to varying extents within the different pharmacies. Interviews revealed mixed views on delegation. Some pharmacists presented positive attitudes towards delegation while others were concerned about maintaining accountability for delegated tasks, particularly in terms of accuracy checking of dispensed medication. Other pharmacists noted the ability to delegate was not a skill they found inherently easy. Comparison of observation and interview data highlighted discrepancies between tasks pharmacists perceived they delegated and what they actually delegated. CONCLUSIONS: Effective delegation can potentially promote better management of workload to provide pharmacists with additional time to spend on cognitive pharmaceutical services. To do this, pharmacists' reluctance to delegate must be addressed. Lack of insight into own practice might be helped by self-reflection and feedback from staff. Also, a greater understanding of legal accountability in the context of delegation needs to be achieved. Finally, delegation is not just dependent on pharmacists, but also on support staff; ensuring staff are empowered and equipped to take on delegated roles is essential. PMID- 26670718 TI - High Mortality from Blood Stream Infection in Addis Ababa, Ethiopia, Is Due to Antimicrobial Resistance. AB - BACKGROUND: Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa. METHODS: Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time. RESULTS: Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38-25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3-164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3-4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32 7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole. CONCLUSION: Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality. PMID- 26670720 TI - Evolution and emerging future of cytoreducxtive surgery and hyperthermic intraperitoneal chemoperfusion in gastric cancer: From treating the incurable to preventing recurrence. AB - The number of new gastric cancer (GC) cases is decreasing, and these patients have longer survival thanks to new oncological treatments. In advanced GC a common evolution of this neoplasm is peritoneal metastases (PM). In the past this finding meant no chance for cure. However, today, using high quality operations and HIPEC, we are able to increase the number of patients treated with curative intention. New options in the diagnosis of PM, tumour susceptibility for different drugs, importance of quality of life, usage in ascites treatment, diagnostic tools in image-guided surgery, new targeted therapies and analysis of currently ongoing trials are presented together with today's knowledge of HIPEC efficacy in order to evaluate gastric PM. HIPEC is an effective tool in the treatment of selected patients with PM from GC. Together with new diagnostic options such as targeted therapies, HIPEC may improve the prognosis of these patients, not only by treating clinically manifest carcinomatosis, but also in the prophylactic setting, addressing occult peritoneal seeding. PMID- 26670721 TI - Atypical defects resulting in growth hormone insensitivity. AB - Besides four well-documented genetic causes of GH insensitivity (GHI) (GHR, STAT5B, IGF1, IGFALS defects), several other congenital and acquired conditions are associated with GHI. With respect to its anabolic actions, GH induces transcription of IGF1, IGFBP3 and IGFALS through a complex regulatory cascade including GH binding to its receptor (GHR), activation of JAK2 and phosphorylation of STAT5b, which then trafficks to the nucleus. GH also activates the MAPK and PI3K pathways. The synthesis of GHR can be reduced by estrogen deficiency or corticosteroid excess, and is possibly decreased in African pygmies. An increased degradation of GHRs because of overexpression of cytokine inducible SH2-containing protein (CIS) was suggested for some children with idiopathic short stature. Effects on several downstream components of GH signaling were observed for FGF21, cytokines, sepsis, fever and chronic renal failure. In Noonan syndrome and other "rasopathies" the activation of the RAS-RAF MAPK-ERK pathway leads to inhibition of the JAK/STAT pathway. In contrast, fibroblasts from tall patients with Sotos syndrome showed a downregulation of this axis. Experimental and clinical evidence suggests that the NF-kappaB pathway plays a role in GH signaling. In a patient with an IkappaBalpha mutation presenting with short stature, GHI, severe immune deficiency and other features, NF-kappaB nuclear transportation and STAT5 and PI3K expression and activity were reduced. A patient with a mosaic de novo duplication of 17q21-25 presented with several congenital anomalies, GHI and mild immunodeficiency. Studies in blood lymphocytes showed disturbed signaling of the CD28 pathway, involving NF-kappaB and related proteins. Functional studies on skin fibroblasts revealed that NF kappaB activation, PI3K activity and STAT5 phosphorylation in response to GH were suppressed, while the sensitivity to GH in terms of MAPK phosphorylation was increased. The expression of one of the duplicated genes, PRKCA, was significantly higher than in control cells, which might be the cause of this clinical syndrome. PMID- 26670722 TI - Structural community factors and sub-optimal engagement in HIV care among low income women in the Deep South of the USA. AB - This study describes the ways in which poverty and other structural factors create a risk environment for sub-optimal engagement in HIV care among low-income women living with HIV in the Southern USA, contributing to existing health disparities. We conducted a qualitative study in 2012, involving in-depth interviews with 14 stakeholders (service providers and representatives of community-based organisations) and 7 focus-group discussions with 46 women living with HIV (89% African American). A thematic approach in the context of the social ecological model guided data analysis. Data were coded and analysed using NVivo qualitative software. The findings suggested that structural community factors, such as poverty, poor employment opportunities, limited access to healthcare resources, stigma, transportation challenges and access to illicit substances, may work independently and in synergy to impact women's health seeking behaviour and decision-making, thereby influencing their ability to engage in HIV care. Interventions designed to improve engagement in HIV care should address structural factors to bolster low-income women's ability to engage in care. PMID- 26670723 TI - The Burden of Major Adverse Cardiac Events and Antiplatelet Prevention in Patients with Coronary or Peripheral Arterial Disease. AB - BACKGROUND: Patients with a history of a cardiovascular (CV) disease are at high risk of suffering secondary major adverse cardiac events (MACE), namely death, nonfatal myocardial infarction (MI), stroke, symptomatic pulmonary embolism, CV and all-cause hospitalization, and bleeding. METHODS: A comprehensive review of the literature was conducted to review the epidemiology and burden of MACE in patients with coronary or peripheral arterial disease (CAD or PAD) in Europe and other ex-US regions. Relevant articles published between 2003 and 2013 were retrieved from PubMed and other sites. RESULTS: MACE incidence and prevalence in patients with CAD or PAD were increased by at least 1.4-fold compared with matched controls with no CV disease. In patients with CAD, MACE mostly occurred within 30 days of primary percutaneous coronary intervention; incidence decreased with time. Increased oxidative stress in coronary and peripheral arteries, diabetes, and chronic kidney disease were identified as the main risk factors for MACE in patients with CAD and PAD. Registry data showed that, although preventive antiplatelet therapy was prescribed at high rates, a large proportion (9-56%) of patients did not receive treatment. Furthermore, adherence to treatment declined over time, potentially leading to disease worsening. CONCLUSION: Despite gaps in the literature, this assessment showed that MACE's risk is substantial among patients with CAD or PAD and that the use of preventive therapies is suboptimal. Development of additional preventive therapies for these patients is warranted. PMID- 26670724 TI - Health outcomes associated with illicit prescription opioid injection: A systematic review. AB - Prescription opioid injection is a growing concern among people who use illicit drugs. Little is known about the potential health-related harms of injecting prescription opioids. Therefore, the authors undertook a systematic review to identify health outcomes associated with injecting prescription opioids. PubMed, Ovid MEDLINE(r), EMBASE, Journals@Ovid, CINAHL, PsycInfo, Web of Science(r) Core Collection, CAB Direct, and ERIC databases were searched to identify English articles published between January 1990 and February 2015 that matched the inclusion criteria. Potentially relevant articles were those examining a clinical health outcome among people who use illicit drugs, in which a sub-group injects prescription opioids. The International Classification of Diseases (ICD-10) was used to clinically classify health outcomes. In total, 31 studies that met the inclusion criteria were identified and summarized. A modified version of the Downs and Black checklist was used to assess individual study quality and identify sources of bias. Findings supported associations between prescription opioid injection and hepatitis C infection, substance dependence and other mental health indicators, and lower general health. Associations with human immunodeficiency virus, overdose, and cutaneous infection were less consistent and varied according to prescription opioid type(s). Several potential sources of bias were identified as well as a need for more longitudinal research and more rigorous confounding adjustment. The current findings highlight a need to consider the growing popularity of prescription opioid injection in efforts to reduce drug-related harm among people who inject drugs. PMID- 26670725 TI - Mono- to few-layered graphene oxide embedded randomness assisted microcavity amplified spontaneous emission source. AB - The realization of optoelectronic devices using two-dimensional materials such as graphene and its intermediate product graphene oxide (GO) is extremely challenging owing to the zero band gap of the former. Here, a novel amplified spontaneous emission (ASE) system based on a GO-embedded all-dielectric one dimensional photonic crystal (1DPhC) micro-resonator is presented. The mono- to few-layered GO sheet is inserted within a microcavity formed by two 5-bilayered SiO2/SnO2 Bragg reflectors. Significantly enhanced photoluminescence (PL) emission of GO embedded in 1DPhC is explicated by studying the electric field confined within the micro-resonator using the transfer matrix method. The inherent randomness, due to fabrication limitations, in the on-average periodic 1DPhC is exploited to further enhance the PL of the optically active micro resonator. The 1DPhC and randomness assisted field confinement reduces the ASE threshold of the mono- to few-layered weak emitter making the realization of an ASE source feasible. Consequently, ASE at the microcavity resonance and at the low-frequency band-edge of photonic stop-band is demonstrated. Variation of the detection angle from 5 degrees to 30 degrees , with respect to the sample surface normal allows reallocation of the defect mode ASE peak over a spectral range of 558-542 nm, making the GO-incorporated 1DPhC a novel and attractive system for integrated optic applications. PMID- 26670732 TI - Successful management of multilineage autoimmune cytopenia complicated with severe infection and deep vein thrombosis in a patient with Hodgkin lymphoma post autologous hematopoietic stem cell transplantation. AB - Autoimmune cytopenia (AIHA, AITP or AIN) were uncommon paraneoplastic manifestations of HL and have been recognized in patients after HSCT with dismal outcome. We presented a case of 16-yr-old male with Hodgkin's lymphoma who developed severe AIC involving all three cell lineages after autologus bone marrow transplantation. No disease relapse was noted. Treatments with steroid, IVIG and immunosuppresants were in vain and the disease course was complicated with sepsis and deep vein thrombosis. Rituximab was administered along with broad spectrum antibiotics and low-molecular weight heparin. The condition became stable and pancytopenia recovered after four doses of rituximab treatment. Severe multi-lineage AIC post HSCT is usually refractory to first-line treatment and difficult to manage. Second-line treatment, such as rituximab, and dedicated care for pancytopenia-induced or treatment-related complications may provide a better outcome. PMID- 26670733 TI - Fluorescent Labeling of Plasmid DNA and mRNA: Gains and Losses of Current Labeling Strategies. AB - Live-cell imaging has provided the life sciences with insights into the cell biology and dynamics. Fluorescent labeling of target molecules proves to be indispensable in this regard. In this Review, we focus on the current fluorescent labeling strategies for nucleic acids, and in particular mRNA (mRNA) and plasmid DNA (pDNA), which are of interest to a broad range of scientific fields. By giving a background of the available techniques and an evaluation of the pros and cons, we try to supply scientists with all the information needed to come to an informed choice of nucleic acid labeling strategy aimed at their particular needs. PMID- 26670734 TI - The cation channel TRPA1 tunes mosquito thermotaxis to host temperatures. AB - While most animals thermotax only to regulate their temperature, female mosquitoes are attracted to human body heat during pursuit of a blood meal. Here we elucidate the basic rules of Aedes aegypti thermotaxis and test the function of candidate thermoreceptors in this important behavior. We show that host seeking mosquitoes are maximally attracted to thermal stimuli approximating host body temperatures, seeking relative warmth while avoiding both relative cool and stimuli exceeding host body temperature. We found that the cation channel TRPA1, in addition to playing a conserved role in thermoregulation and chemosensation, is required for this specialized host-selective thermotaxis in mosquitoes. During host-seeking, AaegTRPA1(-/-) mutants failed to avoid stimuli exceeding host temperature, and were unable to discriminate between host-temperature and high temperature stimuli. TRPA1-dependent tuning of thermotaxis is likely critical for mosquitoes host-seeking in a complex thermal environment in which humans are warmer than ambient air, but cooler than surrounding sun-warmed surfaces. PMID- 26670736 TI - Soft drinks industry accuses doctors of having financial interest in pushing for sugar tax. PMID- 26670735 TI - Mechanisms of ribosome stalling by SecM at multiple elongation steps. AB - Regulation of translating ribosomes is a major component of gene expression control network. In Escherichia coli, ribosome stalling by the C-terminal arrest sequence of SecM regulates the SecA-dependent secretion pathway. Previous studies reported many residues of SecM peptide and ribosome exit tunnel are critical for stalling. However, the underlying molecular mechanism is still not clear at the atomic level. Here, we present two cryo-EM structures of the SecM-stalled ribosomes at 3.3-3.7 A resolution, which reveal two different stalling mechanisms at distinct elongation steps of the translation cycle: one is due to the inactivation of ribosomal peptidyl-transferase center which inhibits peptide bond formation with the incoming prolyl-tRNA; the other is the prolonged residence of the peptidyl-RNA at the hybrid A/P site which inhibits the full-scale tRNA translocation. These results demonstrate an elegant control of translation cycle by regulatory peptides through a continuous, dynamic reshaping of the functional center of the ribosome. PMID- 26670738 TI - Operational Principles for the Dynamics of the In Vitro ParA-ParB System. AB - In many bacteria the ParA-ParB protein system is responsible for actively segregating DNA during replication. ParB proteins move by interacting with DNA bound ParA-ATP, stimulating their unbinding by catalyzing hydrolysis, that leads to rectified motion due to the creation of a wake of depleted ParA. Recent in vitro experiments have shown that a ParB covered magnetic bead can move with constant speed over a DNA covered substrate that is bound by ParA. It has been suggested that the formation of a gradient in ParA leads to diffusion-ratchet like motion of the ParB bead but how it forms and generates a force is still a matter of exploration. Here we develop a deterministic model for the in vitro ParA-ParB system and show that a ParA gradient can spontaneously form due to any amount of initial spatial noise in bound ParA. The speed of the bead is independent of this noise but depends on the ratio of the range of ParA-ParB force on the bead to that of removal of surface bound ParA by ParB. We find that at a particular ratio the speed attains a maximal value. We also consider ParA rebinding (including cooperativity) and ParA surface diffusion independently as mechanisms for ParA recovery on the surface. Depending on whether the DNA covered surface is undersaturated or saturated with ParA, we find that the bead can accelerate persistently or potentially stall. Our model highlights key requirements of the ParA-ParB driving force that are necessary for directed motion in the in vitro system that may provide insight into the in vivo dynamics of the ParA-ParB system. PMID- 26670737 TI - Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress. AB - The role of nanotopographical extracellular matrix (ECM) cues in vascular endothelial cell (EC) organization and function is not well-understood, despite the composition of nano- to microscale fibrillar ECMs within blood vessels. Instead, the predominant modulator of EC organization and function is traditionally thought to be hemodynamic shear stress, in which uniform shear stress induces parallel-alignment of ECs with anti-inflammatory function, whereas disturbed flow induces a disorganized configuration with pro-inflammatory function. Since shear stress acts on ECs by applying a mechanical force concomitant with inducing spatial patterning of the cells, we sought to decouple the effects of shear stress using parallel-aligned nanofibrillar collagen films that induce parallel EC alignment prior to stimulation with disturbed flow resulting from spatial wall shear stress gradients. Using real time live-cell imaging, we tracked the alignment, migration trajectories, proliferation, and anti-inflammatory behavior of ECs when they were cultured on parallel-aligned or randomly oriented nanofibrillar films. Intriguingly, ECs cultured on aligned nanofibrillar films remained well-aligned and migrated predominantly along the direction of aligned nanofibrils, despite exposure to shear stress orthogonal to the direction of the aligned nanofibrils. Furthermore, in stark contrast to ECs cultured on randomly oriented films, ECs on aligned nanofibrillar films exposed to disturbed flow had significantly reduced inflammation and proliferation, while maintaining intact intercellular junctions. This work reveals fundamental insights into the importance of nanoscale ECM interactions in the maintenance of endothelial function. Importantly, it provides new insight into how ECs respond to opposing cues derived from nanotopography and mechanical shear force and has strong implications in the design of polymeric conduits and bioengineered tissues. PMID- 26670739 TI - A geostatistical analysis of the association between armed conflicts and Plasmodium falciparum malaria in Africa, 1997-2010. AB - BACKGROUND: The absence of conflict in a country has been cited as a crucial factor affecting the operational feasibility of achieving malaria control and elimination, yet mixed evidence exists on the influence that conflicts have had on malaria transmission. Over the past two decades, Africa has seen substantial numbers of armed conflicts of varying length and scale, creating conditions that can disrupt control efforts and impact malaria transmission. However, very few studies have quantitatively assessed the associations between conflicts and malaria transmission, particularly in a consistent way across multiple countries. METHODS: In this analysis an explicit geostatistical, autoregressive, mixed model is employed to quantitatively assess the association between conflicts and variations in Plasmodium falciparum parasite prevalence across a 13-year period in sub-Saharan Africa. RESULTS: Analyses of geolocated, malaria prevalence survey variations against armed conflict data in general showed a wide, but short-lived impact of conflict events geographically. The number of countries with decreased P. falciparum parasite prevalence (17) is larger than the number of countries with increased transmission (12), and notably, some of the countries with the highest transmission pre-conflict were still found with lower transmission post conflict. For four countries, there were no significant changes in parasite prevalence. Finally, distance from conflicts, duration of conflicts, violence of conflict, and number of conflicts were significant components in the model explaining the changes in P. falciparum parasite rate. CONCLUSIONS: The results suggest that the maintenance of intervention coverage and provision of healthcare in conflict situations to protect vulnerable populations can maintain gains in even the most difficult of circumstances, and that conflict does not represent a substantial barrier to elimination goals. PMID- 26670740 TI - Case of familial Mediterranean fever presenting with constant abdominal pain. PMID- 26670741 TI - Factors regulating quiescent stem cells: insights from the intestine and other self-renewing tissues. AB - Long-lived and self-renewing adult stem cells (SCs) are essential for homeostasis in a wide range of tissues and can include both rapidly cycling and quiescent (q)SC populations. Rapidly cycling SCs function principally during normal tissue maintenance and are highly sensitive to stress, whereas qSCs exit from their quiescent state in response to homeostatic imbalance and regenerative pressure. The regulatory mechanisms underlying the quiescent state include factors essential for cell cycle control, stress response and survival pathways, developmental signalling pathways, and post-transcriptional modulation. Here, we review these regulatory mechanisms citing observations from the intestine and other self-renewing tissues. PMID- 26670742 TI - The propagation of perturbations in rewired bacterial gene networks. AB - What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and sigma-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ~ 70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ~ 20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions. PMID- 26670744 TI - Breast carcinoma and phyllodes tumour: a case series. AB - Malignant transformation of the epithelial component of phyllodes tumours (PT) is rare and only reported in literature as sporadic cases of carcinoma associated with PTs. We report the clinicopathological characteristics of in situ and invasive carcinoma coexisting with PT in 10 patients treated in our institution over an 11-year period from 1992 to 2012. Ten patients with coexisting PT and in situ or invasive carcinoma were identified from our records. Six had carcinoma found within the PT. All were female with a median age of 47 (43-72) years. One patient had a history of PT in the same breast while another had a history of PT in the same breast as well as invasive ductal carcinoma in the contralateral breast. The rest did not have any risk factors of breast cancer. Five patients had a preoperative core needle biopsy performed with the report of a fibroepithelial lesion. The rest of the patients had surgery upfront for their breast masses. Two patients who had ER/PR positive invasive carcinoma received adjuvant hormonal therapy. Patients were followed up for a mean of 3.6 years (9 months-10 years) and all patients were alive and recurrence free. PT associated with carcinoma is rare, and we present a series of cases that add to the limited current literature. It is often difficult to detect the presence of the carcinomatous component preoperatively. Hence, close examination of resected PT specimens must be carried out to allow prompt detection of any associated carcinomas, however rare, such that adequate treatment can be given. PMID- 26670743 TI - Strategies for Coping with Chronic Lower Back Pain in Patients with Long Physiotherapy Wait Time. AB - BACKGROUND Treatment efficacy for the increasing prevalence of back pain is a great challenge for both health care providers and individuals coping with this problem. This study aimed to evaluate pain coping strategies used by primary care patients with chronic lower back pain (CLBP) as a supplementation of medical diagnosis before a physiotherapy programme. MATERIAL AND METHODS A total of 88 people were divided into 3 age groups: young adults (21-40 years old), middle aged adults (41-60 years old), and the elderly (over 60 years old). Data was gathered from rehabilitation centers and primary medical care facilities. A cross sectional design was used. The Coping Strategies Questionnaire (CSQ) was completed before the physiotherapy course. RESULTS Patients complained of CLBP for 11.32+/-6.81 years on average. The most common strategies to cope with back pain included declaring that the pain is manageable, praying and hoping, as well as increased behavioral activity. Statistically significant differences in coping strategies were found between age groups. The elderly patients were more likely to "declare coping with pain" in comparison to the younger age groups (p<0.01). People over 60 years of age were more likely to declare active coping with pain, while young people reported catastrophizing. CONCLUSIONS Patients in different age groups had various difficulties in pain coping. Most of them required support in self-management of pain in addition to physiotherapy. The basic assessment of pain coping strategies should be consistently taken into account and included in rehabilitation protocols in chronic pain treatment. PMID- 26670745 TI - A feasibility study on the effects of Triton X-100 for the in vitro inactivation of Ebola virus on haematological assays. AB - AIMS: The aim of this study was to check the effect of Triton X-100 on various, commonly used haematology test parameters. METHODS: Anonymised blood samples were treated with 10 uL of 10% Triton X-100 per 1 mL of blood. Treated and untreated samples were tested in parallel for blood film morphology, complete blood counts (CBCs), flow cytometry, blood grouping and antibody screens. Samples were also taken in 3.2% citrate tubes for coagulation test analyses. RESULTS: Statistical differences were noted in all CBC parameters apart from the mean cell volume, eosinophil and basophil counts. Platelet counts were significantly different with an apparent rise after the addition of Triton X-100. Samples were noted to have a high red cell fragmentation index. Immunological platelet counting methods using flow cytometry and fluorescent methods showed no significant differences and gave reliable results. Neither flow cytometry for T-cell subsets nor blood grouping/antibody screens were affected by Triton X-100. However, coagulation samples were severely haemolysed prohibiting analysis. CONCLUSIONS: We have demonstrated that the addition of Triton X-100 to haematology blood samples impacts mainly on platelet counts and coagulation studies due to haemolysis. The platelet count is spuriously raised probably due to the presence of red cell fragments. The latter can be circumvented by the use of immunological platelet counting technology. PMID- 26670746 TI - ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma. AB - BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins. METHODS: We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated. RESULTS: ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival. CONCLUSIONS: ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC. PMID- 26670747 TI - Correlation of ERG immunohistochemistry with molecular detection of TMPRSS2-ERG gene fusion. AB - AIMS: TMPRSS2/E26 transformation-specific (ETS) family gene fusion in prostate carcinoma (PCa) can be detected by several methods including immunohistochemistry (IHC) for ETS-related gene (ERG), the diagnostic utility of which has not been clearly defined. METHODS: We explored TMPRSS2-ERG gene rearrangement status in 132 patients with PCa with four detection methods including fluorescence in situ hybridisation for TMPRSS2-ERG fusion, real-time reverse transcription PCR (RT qPCR) for ERG and TMPRSS-ERG fusion transcript mRNA and IHC for ERG. RESULTS: Concordant results were found in 126 cases for the four detection methods and the remaining six cases showed discrepancy in one method: two cases in IHC, three cases in RT-qPCR for ERG and one case in RT-qPCR for fusion transcript. In discordant cases, the majority results were determined as final fusion status. Analysis of discrepancy cases for ERG IHC showed that weak immunoreactivity for ERG should be regarded as equivocal and that even strong immunoreactivity can be false positive. The overall incidence of TMPRSS-ERG gene fusion was 24%. CONCLUSIONS: ERG IHC is a useful surrogate test for the detection of TMPRSS2-ERG gene fusion, but it needs to be interpreted with caution and definite judgement should not be based on IHC alone. A relatively low incidence of TMPRSS2-ERG gene fusion was demonstrated in this Korean cohort. PMID- 26670749 TI - Physician liability issues and telemedicine: Part 2 of 3. PMID- 26670748 TI - Modulation of Hyperosmotic and Immune-Induced Disruption of the Blood-Brain Barrier by the Nitric Oxide System. AB - OBJECTIVES: The role of nitric oxide (NO) in modulating the blood-brain barrier (BBB) is not entirely clear. We examined the effect of different NO synthase (NOS) inhibitors and NO donors on the permeability of the BBB in animals with normally functioning brain blood vessels, following disruption by hyperosmotic mannitol and during immune inflammation. METHODS: We administered L-NAME, aminoguanidine, S-methyl-thiocitrulline (SMT) and 7-indazole (NOS inhibitors) and NOR-4 (an NO donor) into the cerebral ventricle of rats. Disruption of the BBB was induced by intracarotid injection of mannitol (25%). Experimental autoimmune encephalomyelitis (EAE) was induced by brain homogenate. The extent of disruption was evaluated by Evans blue (2%) dye extravasation. RESULTS: L-NAME (a nonspecific NOS inhibitor) and SMT (a neuronal and endothelial NOS inhibitor) increased mannitol-induced disruption of BBB. This effect was inhibited by NO donors. In animals with a normally functioning BBB, none of these inhibitors or NO donors caused a change in the permeability. 7-indazole (a specific neuronal NOS inhibitor) and aminoguanidine (an inducible NOS inhibitor) had no facilitatory effect on BBB permeability, either alone or in combination with hyperosmotic mannitol. Administration of L-NAME and SMT to rats with EAE significantly aggravated the clinical outcome. In contrast, the administration of NOR-4 diminished clinical signs of EAE. CONCLUSION: The NOS system does not play a role in BBB permeability in naive animals. Only endothelial NOS takes part in the facilitation of BBB compromised by mannitol and EAE. Extrinsic NO decreases this facilitatory effect. PMID- 26670750 TI - Endoscopic view of an osteoma of the maxillary sinus. PMID- 26670751 TI - Hemangioma of the soft palate. PMID- 26670752 TI - Pemphigus vulgaris: An underdiagnosed cause of oral ulcer. PMID- 26670753 TI - The Potter technique for cleft lip rhinoplasty. PMID- 26670754 TI - Sensorineural hearing loss in beta-thalassemia patients treated with iron chelation. AB - The predictive value of pure-tone audiometry (PTA) in the early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions testing appears to be more sensitive to cochlear insult than conventional PTA. We conducted a cross-sectional descriptive study to compare the efficacy of distortion-product otoacoustic emissions (DPOAE) testing with that of PTA as a method of audiologic monitoring. Our study group was made up of 159 patients (318 ears)-69 males (43.4%) and 90 females (56.6%), aged 5 to 61 years (mean: 23.59 +/- 12.55). All patients had been diagnosed with either beta-thalassemia major (BTM) or beta-thalassemia intermedia (BTI), and all had received at least 1 year of treatment within the previous year with an iron chelator-either deferasirox, desferrioxamine (deferoxamine in the United States), deferiprone, or a combination of desferrioxamine and deferiprone. PTA and DPOAE evaluations were performed by the same audiologist using the same audiometer for all patients. In the right ears, the overall incidence of ototoxicity as manifested by sensorineural hearing loss was 39.0% on PTA and 22.0% on DPOAE testing; in the left ears, the corresponding figures were 27.7 and 19.5%, respectively. There were no statistically significant differences in the incidence of ototoxicity between the BTM and BTI groups with any of the four different drug regimens on PTA (p = 0.765, p = 0.378, p = 0.265, and p = 0.579, respectively) or on DPOAE testing (p = 0.890, p = 0.263, p = 0.390, and p = 0.340, respectively). Based on these data, we found no significant difference between PTA and DPOAE testing in their ability to detect ototoxicity. We conclude that periodic testing with both PTA and DPOAE is necessary for patients with suspected beta-thalassemia in order arrive at a prompt diagnosis and initiate timely management. PMID- 26670755 TI - Button battery injuries in the pediatric aerodigestive tract. AB - Children with a button battery impaction present with nonspecific symptoms that may account for a delay in medical care. We conducted a retrospective study of the clinical presentation, management, and complications associated with button battery ingestion in the pediatric aerodigestive tract and to evaluate the associated long-term morbidity. We reviewed the medical records of 23 patients who were treated for button battery impaction at our tertiary care children's hospital from Jan. 1, 2000, through July 31, 2013. This population was made up of 14 boys and 9 girls, aged 7 days to 12 years (mean: 4 yr). Patients were divided into three groups based on the site of impaction; there were 9 impactions in the esophagus and 7 each in the nasal cavity and stomach. We compiled information on the type and size of each battery, the duration of the impaction, presenting symptoms, treatment, and outcomes. The mean duration of battery impaction was 40.6, 30.7, and 21.0 hours in the esophagus, nasal cavity, and stomach, respectively. We were able to identify the specific type of battery in 13 cases; 11 of these cases (85%) involved a 3-V 20-mm lithium ion battery, including all cases of esophageal impaction in which the type of battery was identified. The most common presenting signs and symptoms were vomiting (n = 7 [30%]), difficulty feeding (n = 5 [22%]), cough (n = 5), and bloody nasal discharge (n = 5); none of the presenting signs and symptoms predicted the severity of the injury or the outcome. The median length of hospital stay was far greater in the esophageal group (12 days) than in the nasal and stomach groups (1 day each; p = 0.006). Battery impaction in the esophagus for more than 15 hours was associated with a significantly longer postoperative hospital stay than impaction for less than 15 hours (p = 0.04). Esophageal complications included strictures (n = 5), perforation (n = 3), and tracheoesophageal fistula formation (n = 2). Clinicians should consider battery impaction in the upper aerodigestive tract as an emergency that can lead to significant long-term morbidity, and therefore immediate surgical intervention is required. PMID- 26670756 TI - Two cases of sublingual hematoma as a manifestation of child abuse. AB - Common intraoral manifestations of child abuse include tears of the frenula, burns, and pharyngeal perforations. Sublingual hematomas can also occur as a result of trauma, but to the best of our knowledge, only 1 case has been previously described in the context of child abuse. We report 2 new cases of sublingual hematoma in infants that were the result of physical abuse. Cases of sublingual hematoma in infants and children without a clear and legitimate explanation of the cause should prompt consideration of child abuse. PMID- 26670757 TI - Bone-anchored hearing aid implantation in a patient with Goldenhar syndrome. AB - Patients with Goldenhar syndrome exhibit a number of characteristic symptoms, including middle and internal ear malformations that may cause profound hearing loss. Bone-anchored hearing aids have been used to treat these patients in the past, although complications may arise due to the nature of the disease. Herein we present the case of a pediatric patient with Goldenhar syndrome whose hearing aid abutment extruded spontaneously because of poor bone quality, despite adequate thickness. We provide a brief review of the literature and suggest a flexible surgical plan for any syndromic pediatric patient. PMID- 26670758 TI - Core biopsy as a simple and effective diagnostic tool in head and neck focal myositis. AB - Most unilateral head and neck masses are benign, although malignancy is a possibility in some cases. However, there are other rare causes of unilateral neck masses, such as focal myositis, which is a rare, benign condition belonging to the family of inflammatory pseudotumors of the skeletal muscles, with rare presentations in the head and neck region. Focal myositis presents as a rapidly enlarging neck mass that can be misdiagnosed by fine-needle aspiration biopsy and/or radiologic imaging as either an infective or a neoplastic process. To date, there are only 5 reported cases of adult focal myositis of the sternocleidomastoid muscle in the medical literature. In this article, the authors present 2 cases involving patients with focal myositis of the sternocleidomastoid muscle that were successfully diagnosed with core-needle biopsy and managed conservatively. The pros and cons of fine-needle aspiration biopsy and core-needle biopsy are discussed. Based on the authors' results, fine needle aspiration biopsy universally fails to provide the diagnosis of focal myositis. In contrast, core-needle biopsy successfully diagnosed focal myositis in both of our patients. Both of them had complete resolution with conservative management. PMID- 26670759 TI - An unusual tongue base mass in an infant: Tongue base sialolipoma. AB - Sialolipoma is a rare tumor that occurs in the head and neck. We present a case arising from a minor salivary gland in an infant. The 6-month-old infant presented with difficulty swallowing, frequent reflux, and snoring that had been worsening several weeks before presentation. Physical examination showed a large mass arising from the tongue base. The patient was taken to the operating room for transoral removal of a presumed cyst. Histologic examination of the lesion showed a well-circumscribed lesion composed of lobules of mature adipose tissue and nodules of entrapped, non-neoplastic acini and ductules separated by thin, fibrous septae, consistent with a sialolipoma. To the best of our knowledge, this is the first reported case of a sialolipoma at the tongue base in a child. The patient has had no evidence of recurrence at 1 year of follow-up. PMID- 26670760 TI - Nasal obstruction and recurrent sinusitis caused by bilateral pneumatized ethmoid bullae. AB - The presentation of an enlarged pneumatized bulla ethmoidalis (BE) that obstructs the ethmoid infundibulum has not been previously reported. We report such a case in a 23-year-old woman who presented with recurrent acute rhinosinusitis and chronic rhinosinusitis. The obstruction had been caused by inferior and anterior pneumatization of the BE. Surgery was successful in alleviating all symptoms, and the patient remained symptom-free at 10 months of follow-up. We describe the radiologic and endoscopic findings in this case, and we discuss the possible mechanisms by which BE is involved in the pathogenesis of recurrent acute and chronic rhinosinusitis. PMID- 26670761 TI - Reconstruction after resection of a lower lip squamous cell carcinoma with a submental island flap. AB - Lip cancer is the most common malignancy of the oral cavity and the second most common cancer in the head and neck. Typically, squamous cell carcinoma of the lower lip is an ulcerated lesion with raised margins. Surgery is the best treatment for lower lip cancer. The lips are important aesthetically because of their prominent location on the face and functionally because of the essential mechanism of the sphincter in assisting mastication, swallowing, phonation, and expressing emotions. Depending on the location and size of a lip tumor, different types of reconstructive flaps are used. We describe our technique for reconstructing the lower lip with a submental island flap. PMID- 26670762 TI - Raeder syndrome: Paratrigeminal oculosympathetic syndrome presenting as a manifestation of chronic sinusitis. AB - Raeder syndrome (paratrigeminal oculosympathetic syndrome) is a rare clinical entity characterized by ipsilateral trigeminal sensory deficits, ptosis, and miosis, with an absence of anhidrosis secondary to interruption of the postganglionic oculosympathetic pathway. Going back to its original description, this constellation of physical examination findings has historically been associated with intracranial pathology involving the middle cranial fossa. Understanding this pathway is important in distinguishing Raeder syndrome from Horner syndrome, as the presentation of the former is now recognized to accompany a number of other disease entities in the head and neck region. We present an unusual case of Raeder syndrome associated with bacterial sinusitis, and we discuss its management and review the literature. PMID- 26670763 TI - Facial nerve neurofibroma presenting with external auditory canal tumor and facial palsy. PMID- 26670764 TI - Pleomorphic adenoma of the frontal sinus masquerading as a mucocele. AB - Pleomorphic adenoma is the most common type of benign salivary gland tumor. It can also be found in the larynx, ear, neck, and nasal septum. It is rarely found in the maxillary sinus, and it has never been reported in the frontal sinus. We report a case of pleomorphic adenoma of the frontal sinus that masqueraded as a mucocele. We discuss the clinical presentation, diagnosis, and treatment of this patient, and we review the literature. PMID- 26670765 TI - Sensorineural hearing loss associated with a factitious disorder. AB - Factitious disorders are characterized by intentionally abnormal physical and/or psychological behavior, and affected patients often make up their symptoms and clinical histories. The most serious and chronic type of factitious disorder is Munchausen syndrome. We report the case of a 24-year-old woman with a 2-year history of sensorineural hearing loss (SNHL) who later confessed to feigning her hearing loss. She was eventually diagnosed with a factitious disorder. During those 2 years, she was able to induce her SNHL by exposing herself to excessive noise or high doses of aspirin. To the best of our knowledge, this is the first report describing an association between a factitious disorder and SNHL. PMID- 26670766 TI - Clinical Presentation and Multi-Parametric Screening Surrogates of Ischemic Stroke Patients Suffering from Infective Endocarditis. AB - BACKGROUND: Infective endocarditis (IE) represents a life-threatening condition due to complications like cardiac failure and thromboembolism. In ischemic stroke, IE formally excludes patients from approaches addressing the recanalization of occluded vessels, challenging decision-making in the early phase of hospitalization. This study aimed at the rate and clinical course of stroke patients with IE and explored clinical, imaging-based and serum parameters, which would allow early identification. METHODS: A hospital-based registry containing 1,531 ischemic stroke patients was screened for IE identified by echocardiography. In addition to clinical parameters, patterns of cerebral manifestation as well as a variety of inflammatory serum and myocardial markers were analyzed concerning their predictive impact for identifying affected patients. RESULTS: IE was found in 26 patients (1.7%) and was associated with an increased body temperature and cardiac murmurs. Patients suffering from IE demonstrated a more severe clinical affection at hospital discharge and an impaired symptom decline during hospitalization, further deteriorated by the use of systemic thrombolysis. Distribution of cerebral infarction patterns did not differ between the groups. C-reactive protein (CRP) and leukocyte count as well as troponin and myoglobin, taken at hospital admission, were found to be significantly associated with IE. CONCLUSIONS: IE in stroke patients is associated with worse clinical outcome, complicated by intravenously applied thrombolysis, and therefore needs to be screened during the early phase of hospitalization. Increased serum levels of CRP and leukocyte count in combination with an increased body temperature or abnormal cardiac murmurs should entail rapid initiation of further diagnostics, that is, transoesophageal echocardiography. PMID- 26670767 TI - Trends and outcomes of postpartum haemorrhage, 2003-2011. AB - BACKGROUND: While rates of postpartum haemorrhage (PPH) have continued to rise, it is not clear if the association with other morbidity and transfusion has changed over time. This study explores the recent trend in postpartum haemorrhage and whether postpartum haemorrhage is associated with increased transfusions or adverse outcomes over time. METHODS: Linked birth and hospital data were used to examine ICD-10 AM coded PPH and outcomes in maternal birth admission records, 2003--2011 in hospitals in New South Wales (NSW), Australia (N = 818,965 pregnancies). Trends were calculated on the whole population, and among subgroups, and tested using the Cochran Armitage test for trend. Logistic regression models were developed separately for vaginal and caesarean births, and for a maternal morbidity composite indicator (excluding transfusion) and red cell transfusion. Adjusted odds ratios (aOR) for each year relative to 2003 and 95% confidence intervals (CI) are presented with adjustment for maternal (eg. age, country of birth) and pregnancy factors (eg. parity, interventions, pregnancy complications). RESULTS: Overall, there was a significant increase in the PPH rate, from 6.1% in 2003 to 8.3% in 2011 (p < 0.0001). Crude rates of postpartum haemorrhage with transfusion increased from 0.75% (n = 636) to 1.21% (n = 1145) (p < 0.0001) while crude rates of postpartum haemorrhage with maternal morbidity increased from 0.18% (n = 149) to 0.23% (n = 221) (p = 0.02). Having accounted for maternal and pregnancy factors, there were significant overall decreases in the odds of morbidity among women with a PPH delivering vaginally (in 2006, 2007 and 2010, aORs were 0.70 (95 % CI 0.52, 0.96) 0.69 (0.51, 0.94) and 0.64 (0.47, 0.87) relative to 2003; p < 0.05), and no significant decrease among women delivered by caesarean section (aOR 0.87 (0.58, 1.29) in 2011; p = 0.37). Among women with a PPH delivering vaginally, there was a trend towards a non-linear increase in the adjusted odds of transfusion by birth year. Compared to women who had vaginal births with PPH in 2003, the adjusted odds for transfusion was between 1.1 and 1.2 fold higher for those with a PPH delivering vaginally in 2007, 2009, 2010 and 2011. However there was no significant trend amongst caesarean births (aOR 0.84 (0.66, 1.06) in 2011; p = 0.29). CONCLUSIONS: PPH has become more frequent, however this has not been associated with a clear pattern of increased severe maternal morbidity. This suggests that the increase in PPH may represent fewer severe haemorrhages, better management of severe haemorrhage or better recording of PPH. The increase in transfusions following vaginal births with PPH warrants further investigation. PMID- 26670768 TI - Planarized Intramolecular Charge Transfer: A Concept for Fluorophores with both Large Stokes Shifts and High Fluorescence Quantum Yields. AB - Fluorophores were successfully used in several areas of chemistry and biochemistry. For many purposes, however, it is necessary that the fluorescence compound features a high fluorescence quantum yield as well as a large Stokes shift. The latter is, for example, achieved by the use of a twisted intramolecular charge-transfer (TICT) compound, which shows a twisted geometry in the excited state. However, the higher the twisting is, the lower becomes in general the fluorescence quantum yield as the resulting emission from the twisted state is forbidden. In order to escape this dilemma, we propose the model of planarized intramolecular charge-transfer (PLICT) states. These compounds are completely twisted in the ground states and planar in the excited states. By means of quantum chemical calculations (time-dependent (TD)-B3LYP and CC2) and experimental studies, we could demonstrate that 1-aminoindole and its derivatives form photoinduced PLICT states. They show both very large Stokes shifts (nu~ =9000-13 500 cm(-1) , i.e., lambda=100-150 nm) and high fluorescence quantum yields. These characteristics and their easy availability starting from the corresponding indoles, make them very attractive for the use as optical switches in various fields of chemistry as well as biological probes. PMID- 26670769 TI - Qualitative and mixed methods in systematic reviews. PMID- 26670770 TI - Surface-enhanced Raman spectroscopy in 3D electrospun nanofiber mats coated with gold nanorods. AB - Nanofibers functionalized by metal nanostructures and particles are exploited as effective flexible substrates for surface-enhanced Raman scattering (SERS) analysis. Their complex three-dimensional structure may provide Raman signals enhanced by orders of magnitude compared to untextured surfaces. Understanding the origin of such improved performances is therefore very important for pushing nanofiber-based analytical technologies to their upper limit. Here, we report on polymer nanofiber mats which can be exploited as substrates for enhancing the Raman spectra of adsorbed probe molecules. The increased surface area and the scattering of light in the nanofibrous system are individually analyzed as mechanisms to enhance Raman scattering. The deposition of gold nanorods on the fibers further amplifies Raman signals due to SERS. This study suggests that Raman signals can be finely tuned in intensity and effectively enhanced in nanofiber mats and arrays by properly tailoring the architecture, composition, and light-scattering properties of the complex networks of filaments. PMID- 26670771 TI - Emerging flow injection mass spectrometry methods for high-throughput quantitative analysis. AB - Where does flow injection analysis mass spectrometry (FIA-MS) stand relative to ambient mass spectrometry (MS) and chromatography-MS? Improvements in FIA-MS methods have resulted in fast-expanding uses of this technique. Key advantages of FIA-MS over chromatography-MS are fast analysis (typical run time <60 s) and method simplicity, and FIA-MS offers high-throughput without compromising sensitivity, precision and accuracy as much as ambient MS techniques. Consequently, FIA-MS is increasingly becoming recognized as a suitable technique for applications where quantitative screening of chemicals needs to be performed rapidly and reliably. The FIA-MS methods discussed herein have demonstrated quantitation of diverse analytes, including pharmaceuticals, pesticides, environmental contaminants, and endogenous compounds, at levels ranging from parts-per-billion (ppb) to parts-per-million (ppm) in very complex matrices (such as blood, urine, and a variety of foods of plant and animal origin), allowing successful applications of the technique in clinical diagnostics, metabolomics, environmental sciences, toxicology, and detection of adulterated/counterfeited goods. The recent boom in applications of FIA-MS for high-throughput quantitative analysis has been driven in part by (1) the continuous improvements in sensitivity and selectivity of MS instrumentation, (2) the introduction of novel sample preparation procedures compatible with standalone mass spectrometric analysis such as salting out assisted liquid-liquid extraction (SALLE) with volatile solutes and NH4(+) QuEChERS, and (3) the need to improve efficiency of laboratories to satisfy increasing analytical demand while lowering operational cost. The advantages and drawbacks of quantitative analysis by FIA-MS are discussed in comparison to chromatography-MS and ambient MS (e.g., DESI, LAESI, DART). Generally, FIA-MS sits 'in the middle' between ambient MS and chromatography-MS, offering a balance between analytical capability and sample analysis throughput suitable for broad applications in life sciences, agricultural chemistry, consumer safety, and beyond. PMID- 26670772 TI - Comparative study of the oxidation behavior of sulfur-containing amino acids and glutathione by electrochemistry-mass spectrometry in the presence and absence of cisplatin. AB - Small sulfur-containing compounds are involved in several important biochemical processes, including-but not limited to-redox regulation and drug conjugation/detoxification. While methods for stable redox pairs of such compounds (thiols/disulfides) are available, analytical data on more labile and short-lived redox intermediates are scarce, due to highly challenging analytical requirements. In this study, we employ the direct combination of reagentless electrochemical oxidation and mass spectrometric (EC-MS) identification for monitoring oxidation reactions of cysteine, N-acetylcysteine, methionine, and glutathione under simulated physiological conditions (pH 7.4, 37 degrees C). For the first time, all theoretically expected redox intermediates-with only one exception-are detected simultaneously and in situ, including sulfenic, sulfinic, and sulfonic acids, disulfides, thiosulfinates, thiosulfonates, and sulfoxides. By monitoring the time/potential-dependent interconversion of sulfur species, mechanistic oxidation routes are confirmed and new reactions detected, e.g., sulfenamide formation due to reaction with ammonia from the buffer. Furthermore, our results demonstrate a highly significant impact of cisplatin on the redox reactivity of sulfur species. Namely, the amount of thiol oxidation to sulfonic acid via sulfenic and sulfinic acid intermediates is diminished for glutathione in the presence of cisplatin in favor of the disulfide formation, while for N acetylcysteine the contrary applies. N-acetylcysteine is the only ligand which displays enhanced oxidation currents upon cisplatin addition, accompanied by increased levels of thiosulfinate and thiosulfonate species. This is traced back to thiol reactivity and highlights the important role of sulfenic acid intermediates, which may function as a switch between different oxidation routes. PMID- 26670773 TI - Prevalence of anthelmintic resistance on Lithuanian sheep farms assessed by in vitro methods. AB - BACKGROUND: This study examines the prevalence of drug resistance in gastrointestinal nematodes to macrocyclic lactones (ML) and benzimidazoles (BZ) in Lithuanian sheep using sensitive and precise in vitro methods. The survey was conducted from August 2013 to November 2014. Thirty-three farms with sheep previously treated with BZ and ivermectin (IVM) were included in the study. On 12 farms where only BZ were used, egg hatch discrimination dose testing (EHDDT) was conducted to detect anthelmintic resistance (AR) to BZ. On eight farms where only ML were used, micro agar larval development testing (MALDT) was conducted to detect AR to ivermectin (IVM). On the remaining 13 farms, where both classes of drugs were used, EHDDT and MALDT were both applied to detect multidrug resistance to BZ and IVM. RESULTS: BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs. CONCLUSIONS: The present study demonstrates the existence of AR to BZ and ML on Lithuanian sheep farms thus confirming results in a previous in vivo study. Cases of multi-drug resistance were recorded in the present study and require further consideration. An appropriate strategy for anthelmintic treatment, measures to prevent gastrointestinal nematode infection and a better understanding of the management practices associated with resistance may slow down further development of AR. PMID- 26670775 TI - Removals of non-analogous OTC and BaP in AMCBR with and without primary substrate. AB - Anaerobic biodegradation of mixed non-analogous two substrates was studied in a binary system with and without the primary substrate using an anaerobic multichamber bed (AMCBR). In the binary mixture, the biodegradation of less degradable oxytetracycline (OTC) was restarted in the presence of more degradable benzo[a]pyrene (BaP) in the initial runs of the AMCBR, but enhanced biodegradation of the more recalcitrant OTC occurs in the later runs of the AMCBR due to enhanced biomass growth on dual substrates without the primary carbon source. The biodegradation yields of the OTC, BaP were discussed with sole substrate systems and with the dual substrate system in the presence of the primary substrate. The maximum OTC and BaP yields were 93% in Run 3 with the primary substrate, while the maximum BaP and OTC yields were 95%, 98% in Run 3 without the primary substrate. A dual form of the Monod was found to adequately predict the substrate interactions in the binary mixture of OTC and BaP using only the parameters derived from batch experiments. At low BaP (4 mg L(-1)) and OTC (40 mg L(-1)) concentrations, a non-competitive inhibition does not affect the binding of the substrate and so the K(s) were was not affected while the u(max) was lowered. At high BaP (10 mg L(-1)) and OTC (100 mg L(-1)) concentrations, the BaP and OTC were biodegraded according to competitive inhibition with increased K(s) while u(max) was not affected. BaP and OTC were biodegraded according to Haldane at high concentrations (>10 mg L(-1) for BaP, 100 mg L(-1) OTC) where they were used as the sole substrate. PMID- 26670777 TI - Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. AB - The mouse olfactory mucosa is a complex chemosensory tissue composed of multiple cell types, neuronal and non-neuronal. We have here applied RNA-seq hierarchically, in three steps of decreasing cellular heterogeneity: starting with crude tissue samples dissected from the nose, proceeding to flow cytometrically sorted pools of mature olfactory sensory neurons (OSNs), and finally arriving at single mature OSNs. We show that 98.9% of intact olfactory receptor (OR) genes are expressed in mature OSNs. We uncover a hitherto unknown bipartition among mature OSNs. We find that 19 of 21 single mature OSNs each express a single intact OR gene abundantly, consistent with the one neuron-one receptor rule. For the 9 single OSNs where the two alleles of the abundantly expressed OR gene exhibit single-nucleotide polymorphisms, we demonstrate that monoallelic expression of the abundantly expressed OR gene is extremely tight. The remaining two single mature OSNs lack OR gene expression but express Trpc2 and Gucy1b2. We establish these two cells as a neuronal cell type that is fundamentally distinct from canonical, OR-expressing OSNs and that is defined by the differential, higher expression of 55 genes. We propose this tiered experimental approach as a paradigm to unravel gene expression in other cellularly heterogeneous systems. PMID- 26670779 TI - Impact of milling, enzyme addition, and steam explosion on the solid waste biomethanation of an olive oil production plant. AB - Anaerobic digestion is a consolidated bioprocess which can be further enhanced by incorporating an upstream pretreatment unit. The olive oil production produces a large amount of solid waste which needs to be properly managed and disposed. Three different pretreatment techniques were evaluated in regard to their impact on the anaerobic biodegradability: manual milling of olive pomace (OP), enzyme maceration, direct enzyme addition, and thermal hydrolysis of two-phase olive mill waste. The Gompertz equation was used to obtain parameters for comparison purposes. A substrate/inoculum ratio 0.5 was found to be the best to be used in anaerobic batch test with olive pomace as substrate. Mechanical pretreatment of OP by milling increases the methane production rate while keeping the maximum methane yield. The enzymatic pretreatment showed different results depending on the chosen pretreatment strategies. After the enzymatic maceration pretreatment, a methane production of 274 ml CH4 g VS added (-1) was achieved, which represents an improvement of 32 and 71 % compared to the blank and control, respectively. The direct enzyme addition pretreatment showed no improvement in both the rate and the maximum methane production. Steam explosion showed no improvement on the anaerobic degradability of two-phase olive mill waste; however, thermal hydrolysis with no rapid depressurization enhanced notoriously both the maximum rate (50 %) and methane yield (70 %). PMID- 26670778 TI - Ascending aortic replacement for acute type A aortic dissection in octogenarians. AB - OBJECTIVE: The management of acute type A aortic dissection in elderly patients is controversial. This study aimed to investigate the validity of ascending aortic replacement for acute type A aortic dissection in octogenarians compared with younger patients. METHODS: Twenty-five octogenarians, among 117 consecutive patients with acute type A aortic dissection between January 2000 and October 2013 who underwent emergency surgery, were reviewed retrospectively. The median age was 84 years (80-91 years). The patients were six men and 19 women. All 25 patients underwent ascending aortic replacement under deep hypothermic circulatory arrest. In the same period, 55 patients younger than 80 years with acute type A aortic dissection had ascending aortic replacement performed. Clinical data were prospectively entered into our institutional database. Late follow-up was 6.8 +/- 2.8 years and was 100% complete. RESULTS: The 30-day mortality rate was 8% (2/25 patients), which was similar to that in patients younger than 80 years (5%). There were no reoperations in octogenarians and five reoperations in younger patients in the follow-up period. Survival at 1 and 5 years was 80.0 and 59.7% in octogenarians and 90.6 and 81.9% in younger patients, respectively (P = 0.036). CONCLUSION: Ascending aortic replacement for octogenarians with acute type A aortic dissection was successfully performed, resulting in satisfactory early and midterm survival. Aggressive surgical treatment is mandatory for improving the outcome in octogenarians with acute type A aortic dissection. PMID- 26670780 TI - Comparative studies on glycerol monooleate- and phytantriol-based cubosomes containing oridonin in vitro and in vivo. AB - To improve the solubility and bioavailability of oridonin (ORI), glycerol monooleate lipid (GMO)- or phytantriol (PYT)-Poloxamer 407-propylene glycol-water systems were firstly used to develop cubosomes containing ORI for oral delivery. These cubosomes prepared through the fragmentation of bulk gels under homogenization conditions of 1200 bar and nine cycles had a mean particle size of around 200 nm with narrow size distribution, and ORI encapsulation efficiency over 85%. Powder X-ray diffraction and differential scanning calorimetry indicated that ORI was in an amorphous or molecular form in the cubosomes. The internal structures of GMO- and PYT-based cubosomes were revealed by small-angle X-ray scattering as a bi-continuous cubic liquid crystalline phase with Im3m and Pn3m geometry, respectively. About 80% of ORI was released in vitro from GMO- and PYT-based cubosomes at 24 h, showing a sustained release kinetics fitted with Higuchi's equation. The pharmacokinetic study in rats showed that the PYT-based cubosomes significantly enhanced the adsorption of ORI as compared to the GMO based cubosomes and ORI suspension, with evidence of longer half-life and greater relative bioavailability (p < 0.01). Therefore, the PYT-based cubosomes containing ORI might be proposed as a promising candidate carrier for the efficient delivery of drug with therapeutic treatment. PMID- 26670781 TI - Selective Release of Aromatic Heterocycles from Ruthenium Tris(2 pyridylmethyl)amine with Visible Light. AB - Three complexes of the general formula [Ru(TPA)L2](PF6)2 [TPA = tris(2 pyridylmethyl)amine], where L = pyridine (1), nicotinamide (2), and imidazole (3), were prepared and characterized spectroscopically. X-ray crystallographic data were obtained for 1 and 3. Complexes 1-3 show strong absorption in the visible region and selective release of heterocycles upon irradiation with visible light. Time-dependent density functional theory calculations are consistent with the presence of singlet metal-to-ligand charge-transfer bands in the visible region in 1-3. Caged heterocycles 1-3 are highly stable in solution in the dark, including in cell growth media. Cell viability data show no signs of toxicity of 1-3 against PC-3 cells at concentrations up to 100 MUM under light and dark conditions, consistent with Ru(TPA) acting as a nontoxic and effective photocaging group for aromatic heterocycles. PMID- 26670782 TI - Sacral nerve stimulation for fecal incontinence in a patient with anti phospholipid syndrome-related autonomic neuropathy. PMID- 26670783 TI - Mono- and Bis-Alkylation of Glyoxal-Bridged Tetraazamacrocycles Using Mechanochemistry. AB - Glyoxal-bridged bisaminal tetraazamacrocyclic derivatives of 1,4,7,10 tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) can be N-functionalized to incorporate coordinating groups or for conjugation to biomolecules. Herein, we present an improved N-functionalization methodology using mechanochemistry which reduces reaction times in comparison with conventional synthetic routes. A range of six alkyl halides were reacted with cyclen and cyclam bisaminal derivatives in various ratios to form mono- and bis functionalized quaternary ammonium salts. Cross-bridged cyclam, a key intermediate for CB-TE2A, a commonly used chelator in positron emission tomography medical imaging with (64)Cu, has been synthesized using nonconventional synthetic methodologies (grinding and microwave heating) with intermediates characterized by 2D NMR and single crystal XRD. The overall synthesis time of CB-TE2A from cyclam could be shortened to 5 days from the 35 days required for the conventional synthesis. PMID- 26670784 TI - Role of sympathetic nervous system in rat model of chronic visceral pain. AB - BACKGROUND: Changes in central pain modulation have been implicated in generalized pain syndromes such as irritable bowel syndrome (IBS). We have previously demonstrated that reduced descending inhibition unveils a role of sympathoneuronal outflow in decreasing peripheral sensory thresholds, resulting in stress-induced hyperalgesia. We investigated whether sympathetic nervous system (SNS) exacerbation of pain sensation when central pain inhibition is reduced is relevant to chronic pain disorders using a rat colon irritation (CI) model of chronic visceral hypersensitivity with hallmarks of IBS. METHODS: Rats were treated to a series of colorectal balloon distensions (CRD) as neonates resulting in visceral and somatic hypersensitivity and altered stool function that persists into adulthood. The visceral sensitivity was assessed by recording electromyographic (EMG) responses to CRD. Somatic sensitivity was assessed by paw withdrawal thresholds to radiant heat. The effects on the hypersensitivity of (i) inhibiting sympathoneuronal outflow with pharmacological and surgical interventions and (ii) enhancing the outflow with water avoidance stress (WAS) were tested. KEY RESULTS: The alpha2-adrenergic agonist, clonidine, and the alpha1-adrenergic antagonist, prazosin, reduced the visceral hypersensitivity and WAS enhanced the pain. Chemical sympathectomy with guanethidine and surgical sympathectomy resulted in a loss of the chronic visceral hypersensitivity. CONCLUSIONS & INFERENCES: The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes. PMID- 26670785 TI - Factors Impacting Functional Status in Veterans of Recent Conflicts With PTSD. AB - Veterans with posttraumatic stress disorder (PTSD) underwent a systematic evaluation to determine which factors were associated with the degree of functional status. Demographic information, self-report scales, and symptom ratings performed by trained evaluators were investigated in multiple regression models to determine their contribution to functional status. Ninety-six participants were included in the model assessing degree of functional status. Depressive symptoms, a depressive disorder diagnosis, and to a lesser extent, the Clinician-Administered PTSD Scale were selected in the final model that best predicted the degree of functional status. Depressive symptoms significantly affect the function of veterans with PTSD. PMID- 26670786 TI - Moria Revisited: Translation of Moritz Jastrowitz's Description of Pathologic Giddiness. PMID- 26670787 TI - Catatonia in Neurologic and Psychiatric Patients at a Tertiary Neurological Center. AB - This study describes the prevalence, phenomenology, treatment, and outcome of neurological patients and psychiatric patients with catatonia at a tertiary neurological center. Clinical variables included nosological diagnoses and complications. Admission length and days with catatonia were used as outcome measures. Of 2,044 patients who were evaluated prospectively, 68 (3.32%) had catatonia, 42 (61.7%) were neurological patients, 19 (27.9%) were psychiatric patients, and 7 (10.2%) had drug-related diagnoses. Of all patients, the ratio of neurological to psychiatric patients was 3:1. Encephalitis was the most common diagnosis (N=26 [38.2%]), followed by schizophrenia (N=12 [17.6%]). Psychiatric patients exhibited a stuporous type of catatonia (15 [83.3%] versus 14 [33.3%], p>0.001), whereas neurological patients exhibited a mixed form of catatonia (25 [59.5%] versus 1 [5.6], p<0.001). Neurological patients had more complications, longer hospitalizations, and more days with catatonia. A total of 56 patients (82.3%) received lorazepam, and 14 patients (20.5%) underwent ECT. Second- and third-line treatments included amantadine, bromocriptine, and levodopa. Catatonia is a prevalent syndrome that can remit with proper and opportune treatment. PMID- 26670788 TI - Human Trafficking and Psychiatric Education: A Call to Action. PMID- 26670789 TI - Bringing Back Ubuntu. PMID- 26670790 TI - Distillation of photon entanglement using a plasmonic metamaterial. AB - Plasmonics is a rapidly emerging platform for quantum state engineering with the potential for building ultra-compact and hybrid optoelectronic devices. Recent experiments have shown that despite the presence of decoherence and loss, photon statistics and entanglement can be preserved in single plasmonic systems. This preserving ability should carry over to plasmonic metamaterials, whose properties are the result of many individual plasmonic systems acting collectively, and can be used to engineer optical states of light. Here, we report an experimental demonstration of quantum state filtering, also known as entanglement distillation, using a metamaterial. We show that the metamaterial can be used to distill highly entangled states from less entangled states. As the metamaterial can be integrated with other optical components this work opens up the intriguing possibility of incorporating plasmonic metamaterials in on-chip quantum state engineering tasks. PMID- 26670791 TI - Devil in the Details: A Critical Review of "Theoretical Loss". AB - In their review of Internet gambling studies, Auer and Griffiths (J Gambl Stud 30(4), 879-887, 2014) question the validity of using bet size as an indicator of gambling intensity. Instead, in that review and in a response (Auer and Griffiths, J Gambl Stud 31(3), 921-931, 2015) to a previous comment (Braverman et al., J Gambl Stud 31(2), 359-366, 2015), Auer and Griffiths suggested using "theoretical loss" as a preferable measure of gambling intensity. This comment extends and advances the discussion about measures of gambling intensity. In this paper, we describe previously identified problems that Auer and Griffiths need to address to sustain theoretical loss as a viable measure of gambling intensity and add details to the discussion that demonstrate difficulties associated with the use of theoretical loss with certain gambling games. PMID- 26670792 TI - Nicotinamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy. AB - Nicotinamide (vitamin B3) was the first drug selected for cross-model testing by the Operation Brain Trauma Therapy (OBTT) consortium based on a compelling record of positive results in pre-clinical models of traumatic brain injury (TBI). Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Nicotinamide (50 or 500 mg/kg) was delivered intravenously at 15 min and 24 h after injury with subsequent behavioral, biomarker, and histopathological outcome assessments. There was an intermediate effect on balance beam performance with the high (500 mg/kg) dose in the CCI model, but no significant therapeutic benefit was detected on any other motor task across the OBTT TBI models. There was an intermediate benefit on working memory with the high dose in the FPI model. A negative effect of the low (50 mg/kg) dose, however, was observed on cognitive outcome in the CCI model, and no cognitive improvement was observed in the PBBI model. Lesion volume analysis showed no treatment effects after either FPI or PBBI, but the high dose of nicotinamide resulted in significant tissue sparing in the CCI model. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-1 (UCH-L1) in blood at 4 or 24 h after injury. Negative effects (both doses) were detected on biomarker levels of GFAP after FPI and on biomarker levels of UCH-L1 after PBBI. The high dose of nicotinamide, however, reduced GFAP levels after both PBBI and CCI. Overall, our results showed a surprising lack of benefit from the low dose nicotinamide. In contrast, and partly in keeping with the literature, some benefit was achieved with the high dose. The marginal benefits achieved with nicotinamide, however, which appeared sporadically across the TBI models, has reduced enthusiasm for further investigation by the OBTT Consortium. PMID- 26670793 TI - Antioxidant Peptides Identified from Ovotransferrin by the ORAC Method Did Not Show Anti-Inflammatory and Antioxidant Activities in Endothelial Cells. AB - Oxygen radical absorbance capacity (ORAC) is a widely used method of measuring antioxidant capacities of various antioxidant components. Surprisingly, 16 antioxidant peptides previously identified from egg protein ovotransferrin using the ORAC method did not show any anti-inflammatory and antioxidant activities in cells. After simulated gastro-intestinal digestion (GID), several peptide digests significantly reduced the expression of tumor necrosis factor-alpha (TNF-alpha) induced pro-inflammatory intercellular cell adhesion molecule-1 (ICAM-1) by 65.7 +/- 10.4% and vascular cell adhesion molecule-1 (VCAM-1) by 53.5 +/- 9.6% to 61.0 +/- 14.5%, but only GWNI reduced TNF-alpha-activated superoxide generation by 71.0 +/- 12.9% when tested with dihydroethidium (DHE) assay. Mass spectrometer analysis identified two new peptides, GWN and GW, in the GWNI digest; however, only GW reduced TNF-alpha-induced VCAM-1 expression (64.3 +/- 20.6%) significantly compared to the TNF-alpha treated cells. Our study suggested that ORAC lacked biological relevance in assessing bioactive peptides. PMID- 26670794 TI - Association of Polymorphisms in Endothelial Nitric Oxide Synthesis and Renin Angiotensin-Aldosterone System with Developing of Coronary Artery Disease in Bulgarian Patients. AB - AIM: The purpose of this study was to evaluate the association of common polymorphisms in endothelial nitric oxide synthesis (eNOS; G894T) and renin angiotensin-aldosterone system (angiotensin converting enzyme [ACE]-I/D, angiotensinogen-T704C, and angiotensin II receptor type 1-A1166C) as risk factors in the pathogenesis of coronary artery disease (CAD) in Bulgarian patients. METHODS: This study included 171 patients with CAD and 123 control subjects. Polymerase chain reaction-restriction fragment length polymorphism was used for studying the single-nucleotide polymorphisms. Statistical analysis was performed using statistical software PASW for Windows. RESULTS: A significantly higher percentage of the eNOS T894 allele was found in patients with acute coronary syndrome (ACS), compared to controls (p = 0.006) and patients with stable angina pectoris (SAP, p = 0.005). Results from a binary regression analysis suggested that eNOS T allele and ACE D allele carriers were more likely to develop ACS than controls (T allele odds ratio [OR] 2.585, p = 0.024; D allele OR 3.585, p = 0.046) and patients with SAP (T allele OR 2.955, p = 0.009; D allele OR 2.703, p = 0.05). Exploratory evaluation of gene-gene combinations showed a significant association between eNOS-G894T/ACE-I/D and ACS compared to controls (p = 0.022) and patients with SAP (p = 0.017). CONCLUSIONS: The eNOS G894T and ACE I/D polymorphisms are associated with an increased risk of developing ACS after adjusting for classical risk factors for atherosclerosis in the Bulgarian cohort. PMID- 26670796 TI - Correction: Experimental studies on the rheology of cubic blue phases. AB - Correction for 'Experimental studies on the rheology of cubic blue phases' by Rasmita Sahoo et al., Soft Matter, 2016, DOI: . PMID- 26670795 TI - The rise of concurrent care for veterans with advanced cancer at the end of life. AB - BACKGROUND: Unlike Medicare, the Veterans Health Administration (VA) health care system does not require veterans with cancer to make the "terrible choice" between receipt of hospice services or disease-modifying chemotherapy/radiation therapy. For this report, the authors characterized the VA's provision of concurrent care, defined as days in the last 6 months of life during which veterans simultaneously received hospice services and chemotherapy or radiation therapy. METHODS: This retrospective cohort study included veteran decedents with cancer during 2006 through 2012 who were identified from claims with cancer diagnoses. Hospice and cancer treatment were identified using VA and Medicare administrative data. Descriptive statistics were used to characterize the changes in concurrent care, hospice, palliative care, and chemotherapy or radiation treatment. RESULTS: The proportion of veterans receiving chemotherapy or radiation therapy remained stable at approximately 45%, whereas the proportion of veterans who received hospice increased from 55% to 68%. The receipt of concurrent care also increased during this time from 16.2% to 24.5%. The median time between hospice initiation and death remained stable at around 21 days. Among veterans who received chemotherapy or radiation therapy in their last 6 months of life, the median time between treatment termination and death ranged from 35 to 40 days. There was considerable variation between VA medical centers in the use of concurrent care (interquartile range, 16%-34% in 2012). CONCLUSIONS: Concurrent receipt of hospice and chemotherapy or radiation therapy increased among veterans dying from cancer without reductions in the receipt of cancer therapy. This approach reflects the expansion of hospice services in the VA with VA policy allowing the concurrent receipt of hospice and antineoplastic therapies. Cancer 2016;122:782-790. (c) 2015 American Cancer Society. PMID- 26670797 TI - Silanol-Assisted Carbinolamine Formation in an Amine-Functionalized Mesoporous Silica Surface: Theoretical Investigation by Fragmentation Methods. AB - The aldol reaction catalyzed by an amine-substituted mesoporous silica nanoparticle (amine-MSN) surface was investigated using a large molecular cluster model (Si392O958C6NH361) combined with the surface integrated molecular orbital/molecular mechanics (SIMOMM) and fragment molecular orbital (FMO) methods. Three distinct pathways for the carbinolamine formation, the first step of the amine-catalyzed aldol reaction, are proposed and investigated in order to elucidate the role of the silanol environment on the catalytic capability of the amine-MSN material. The computational study reveals that the most likely mechanism involves the silanol groups actively participating in the reaction, forming and breaking covalent bonds in the carbinolamine step. Therefore, the active participation of MSN silanol groups in the reaction mechanism leads to a significant reduction in the overall energy barrier for the carbinolamine formation. In addition, a comparison between the findings using a minimal cluster model and the Si392O958C6NH361 cluster suggests that the use of larger models is important when heterogeneous catalysis problems are the target. PMID- 26670798 TI - Porous three-dimensional graphene foam/Prussian blue composite for efficient removal of radioactive (137)Cs. AB - In this study, a simple one-step hydrothermal reaction is developed to prepare composite based on Prussian blue (PB)/reduced graphene oxide foam (RGOF) for efficient removal of radioactive cesium ((137)Cs) from contaminated water. Scanning electron microscopy and transmission electron microscopy show that cubic PB nanoparticles are decorated on the RGO surface. Owing to the combined benefits of RGOF and PB, the composite shows excellent removal efficiency (99.5%) of (137)Cs from the contaminated water. The maximum adsorption capacity is calculated to be 18.67 mg/g. An adsorption isotherm fit-well the Langmuir model with a linear regression correlation value of 0.97. This type of composite is believed to hold great promise for the clean-up of (137)Cs from contaminated water around nuclear plants and/or after nuclear accidents. PMID- 26670799 TI - [Not Available]. PMID- 26670800 TI - The challenges in producing high-quality clinical evidence. PMID- 26670801 TI - Predicting outcomes: Is there utility in risk scores? AB - PURPOSE: This review discusses the utility of risk scores, specifically, the role of preoperative risk scores in guiding the management of surgical patients, approaches to evaluate the quality of risk scores, and limitations to consider when applying risk scores in clinical practice. PRINCIPAL FINDINGS: This review shows how accurate predictions of perioperative risk can help inform patients and clinicians with respect to decision-making around surgery; identify patients who warrant further specialized investigations, new interventions intended to decrease risk, modifications in planned operative procedures, or intensification of postoperative monitoring; and facilitate fairer comparisons of outcomes between providers and hospitals. A preoperative risk score formally integrates several pieces of clinical information (e.g., age, comorbid disease, laboratory tests) to arrive at an overall estimate of an individual patient's expected risk for specific postoperative adverse events. A good risk score should be simple to incorporate in clinical practice, reliable when applied by different raters, and accurate at predicting postoperative risk. Several analytical methods (e.g., receiver operating characteristic curves, likelihood ratios, risk reclassification tables, observed vs predicted plots) are required to characterize the relevant domains that encompass the prognostic accuracy of a risk score. External validation is critical in determining whether the predictive accuracy of a risk score is preserved when applied to new settings, populations, or outcome events. CONCLUSIONS: Preoperative risk scores help inform perioperative clinical decision-making. Future research must determine how estimates of preoperative risk can be updated with information from the intraoperative period, how risk information should be communicated to patients, and which interventions can improve outcomes among patients within newly identified risk strata. PMID- 26670802 TI - Efficacy of a simple scavenging system for long-term critical care sedation using volatile agent-based anesthesia. PMID- 26670803 TI - A new analgesic paradigm for pediatric tonsillectomy: Are we dragging our heels? PMID- 26670804 TI - An uncommon cause of tricuspid regurgitation: three-dimensional echocardiographic incremental value, surgical and genetic insights. AB - Congenital tricuspid valve disease is a rare defect that includes regurgitation, stenosis and Ebstein's anomaly. We report a case of severe tricuspid regurgitation associated with functional mitral regurgitation in a 47-year-old man with congestive heart failure. Transthoracic echocardiography (TTE) ruled out any Ebstein's anomaly. Three-dimensional TTE revealed a 'tricuspid hole' into the anterior leaflet that was only attached to the tricuspid annulus next to both anteroseptal and anteroposterior commissures. There was no sign of leaflet tear or perforation. The surgical repair of the tricuspid and mitral valves was performed with an optimal result. No sign of endocarditis or rheumatic disease was observed during the intervention. Sequence analysis of GATA4, HEY2 and ZFPM2 genes was performed, but no causative mutation was identified. PMID- 26670805 TI - The on-pump/off-pump saga: an enduring conundrum. PMID- 26670806 TI - State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma. AB - In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC. PMID- 26670807 TI - Indications and pitfalls of sutureless aortic valves: recommendations are welcome. PMID- 26670808 TI - Little Thermodynamic Penalty for the Synthesis of Ultraporous Metal Organic Frameworks. AB - Many metal-organic frameworks (MOFs) of ultrahigh porosity (with molar volumes more than ten times greater than those of the corresponding dense phases) have been synthesized. However, the number of possible structures far exceeds those that have been made. It is logical to ask if there are energetic barriers to the stability of ultraporous MOFs or whether there is little thermodynamic penalty to their formation. Herein, we show that although the molar volumes of MOF-177 and UMCM-1 reach ultrahigh values, their energetic metastability is in the same range (of 7-36 kJ mol(-1)) as that seen previously for other porous materials. These findings suggest that there is little thermodynamic penalty for the synthesis of structures with varying porosity, and hence, ultraporous frameworks are energetically accessible. Therefore, innovative synthesis methods have the possibility to overcome the drawbacks of conventional approaches and greatly extend the number, porosity, and properties of new framework materials. PMID- 26670809 TI - Protoporphyrin Treatment Modulates Susceptibility to Experimental Autoimmune Encephalomyelitis in miR-155-Deficient Mice. AB - We previously identified heme oxygenase 1 (HO-1) as a specific target of miR-155, and inhibition of HO-1 activity restored the capacity of miR-155-/- CD4+ T cells to promote antigen-driven inflammation after adoptive transfer in antigen expressing recipients. Protoporphyrins are molecules recognized for their modulatory effect on HO-1 expression and function. In the present study, we investigated the effect of protoporphyrin treatment on the development of autoimmunity in miR-155-deficient mice. MiR-155-mediated control of HO-1 expression in promoting T cell-driven chronic autoimmunity was confirmed since HO 1 inhibition restored susceptibility to experimental autoimmune encephalomyelitis (EAE) in miR-155-deficient mice. The increased severity of the disease was accompanied by an enhanced T cell infiltration into the brain. Taken together, these results underline the importance of miR-155-mediated control of HO-1 expression in regulating the function of chronically-stimulated T cells in EAE. PMID- 26670810 TI - The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products. AB - In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as EmdogainTM through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications. PMID- 26670811 TI - Biocompatible, Free-Standing Film Composed of Bacterial Cellulose Nanofibers Graphene Composite. AB - In recent years, graphene films have been used in a series of wide applications in the biomedical area, because of several advantageous characteristics. Currently, these films are derived from graphene oxide (GO) via chemical or physical reduction methods, which results in a significant decrease in surface hydrophilicity, although the electrical property could be greatly improved, because of the reduction process. Hence, the comprehensive performance of the graphene films showed practical limitations in the biomedical field, because of incompatibility of highly hydrophobic surfaces to support cell adhesion and growth. In this work, we present a novel fabrication of bacterial cellulose nanofibers/reduced graphene oxide (BC-RGO) film, using a bacterial reduction method. Thus-prepared BC-RGO films maintained excellent hydrophilicity, while electrical properties were improved by bacterial reduction of GO films in culture. Human marrow mesenchymal stem cells (hMSCs) cultured on these surfaces showed improved cellular response with higher cell proliferation on the BC-RGO film, compared to free-standing reduced graphene oxide film without the nanoscale fibrous structure. Furthermore, the cellular adhesion and proliferation were even comparable to that on the tissue culture plate, indicating that the bacterial cellulose nanofibers play a critically contructive role in supporting cellular activities. The novel fabrication method greatly enhanced the biochemical activity of the cells on the surface, which could aid in realizing several potential applications of graphene film in biomedical area, such as tissue engineering, bacterial devices, etc. PMID- 26670812 TI - The current challenges of cardiac arrest: Post cardiac arrest management. PMID- 26670813 TI - Ventilation and gas exchange management after cardiac arrest. AB - For several decades, physicians had integrated several interventions aiming to improve the outcomes in post-cardiac arrest patients. However, the mortality rate after cardiac arrest is still as high as 50%. Post-cardiac arrest syndrome is associated with high morbidity and mortality due to not only poor neurological outcome and cardiovascular failure but also respiratory dysfunction. To minimize ventilator-associated lung injury, protective mechanical ventilation by using low tidal volume ventilation and driving pressure may decrease pulmonary complications and improve survival. Low level of positive end-expiratory pressure (PEEP) can be initiated and titrated with careful cardiac output and respiratory mechanics monitoring. Furthermore, optimizing gas exchange by avoiding hypoxia and hyperoxia as well as maintaining normocarbia may improve neurological and survival outcome. Early multidisciplinary cardiac rehabilitation intervention is recommended. Minimally invasive monitoring techniques, that is, echocardiography, transpulmonary thermodilution method measuring extravascular lung water, as well as transcranial Doppler ultrasound, might be useful to improve appropriate management of post-cardiac arrest patients. PMID- 26670814 TI - What is the proper target temperature for out-of-hospital cardiac arrest? AB - The implementation of target temperature management (TTM) or therapeutic hypothermia has been demonstrated in several major studies to be an effective neuroprotective strategy in postresuscitation care after cardiac arrest. Although several landmark studies found the promising results of lower targeted temperature (32-34 degrees C) in terms of survival and neurological outcomes, recent evidence showed no difference in either survival or long-term neurological outcome when compared with higher targeted temperature (36 degrees C). Thus, recent data suggest that avoiding hyperpyrexia, rather than cooling "per se," may be considered the main therapeutic target to avoid secondary brain damage after out-of-hospital cardiac arrest. Many questions are still debated about the exact protocol of TTM to be used, including whether temperature control is more beneficial than standard of care without active temperature control, the optimal cooling temperature, patient selection, and duration of cooling. The aim of this review article was to discuss the physiology of hypothermia, available cooling methods, and current evidence about the optimal target temperature and timing of hypothermia. PMID- 26670815 TI - Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest. AB - The approach to sedation, analgesia, and neuromuscular blockade during targeted temperature management (TTM) remains largely unstudied, forcing clinicians to adapt previous research from other patient environments. During TTM, very little data guide drug selection, doses, and specific therapeutic goals. Sedation should be deep enough to prevent awareness during neuromuscular blockade, but titration is complex as metabolism and clearance are delayed for almost all drugs during hypothermia. Deeper sedation is associated with prolonged intensive care unit (ICU) and ventilator therapy, increased delirium and infection, and delayed wakening which can confound early critical neurological assessments, potentially resulting in erroneous prognostication and inappropriate withdrawal of life support. We review the potential therapeutic goals for sedation, analgesia, and neuromuscular blockade during TTM; the adverse events associated with that treatment; data suggesting that TTM and organ dysfunction impair drug metabolism; and controversies and potential benefits of specific monitoring. We also highlight the areas needing better research to guide our therapy. PMID- 26670816 TI - Neuroprotective strategies and neuroprognostication after cardiac arrest. AB - Neurocognitive disturbances are common among survivors of cardiac arrest (CA). Although initial management of CA, including bystander cardiopulmonary resuscitation, optimal chest compression, and early defibrillation, has been implemented continuously over the last years, few therapeutic interventions are available to minimize or attenuate the extent of brain injury occurring after the return of spontaneous circulation. In this review, we discuss several promising drugs that could provide some potential benefits for neurological recovery after CA. Most of these drugs have been investigated exclusively in experimental CA models and only limited clinical data are available. Further research, which also considers combined neuroprotective strategies that target multiple pathways involved in the pathophysiology of postanoxic brain injury, is certainly needed to demonstrate the effectiveness of these interventions in this setting. Moreover, the evaluation of neurological prognosis of comatose patients after CA remains an important challenge that requires the accurate use of several tools. As most patients with CA are currently treated with targeted temperature management (TTM), combined with sedative drug therapy, especially during the hypothermic phase, the reliability of neurological examination in evaluating these patients is delayed to 72-96 h after admission. Thus, additional tests, including electrophysiological examinations, brain imaging and biomarkers, have been largely implemented to evaluate earlier the extent of brain damage in these patients. PMID- 26670817 TI - Acid-base optimization during hypothermia. AB - Cardiac arrest (CA) often results in hemodynamic and metabolic compromise with associated poor prognosis. Therapeutic hypothermia (TH) has become the standard of care for CA survivors, decreasing reperfusion injury and intercellular acid base disturbances, with improved neurologic outcomes. These benefits are realized despite a mild acidosis that can potentially occur during TH. By contrast, the severity of acidosis after return of spontaneous circulation (ROSC) must be monitored carefully and managed appropriately. Bicarbonate should be used only in case of severe acidosis and as a continuous infusion. The blood gas samples are usually warmed to 37 degrees C before analysis; hence, it is worth noting that the blood gas values are temperature dependent. Therefore, a calculated correction for values may be necessary. PMID- 26670818 TI - Metabolic and electrolyte disturbance after cardiac arrest: How to deal with it. AB - Cardiac arrest (CA) is a sudden, severe event that causes a cascade of metabolic and electrolyte disturbances throughout the body triggered by a loss of cardiac output. Metabolic disturbances are primarily in the form of mixed metabolic and respiratory acidosis; dysglycaemia; and states of deficiency or excess in potassium, calcium, magnesium and lactate. It is known that persistent metabolic disturbances are associated with poor patient outcome following resuscitation from CA, but this might simply be a reflection of the severity of illness. Moreover, contemporary evidence for the management of metabolic disturbances to improve outcomes in these patients is scarce. Moreover, metabolic disturbances during the early post-resuscitation period remain poorly understood in terms of severity, duration and the influence of their post-resuscitation care and treatment on outcome. Although sufficient data suggest that extreme metabolic disturbances such as hypoglycaemia, severe hyperglycaemia, severe hypokalaemia and hyperkalaemia and hypomagnesaemia likely have a devastating effect and should be avoided, randomised controlled trial evidence is clearly need for the management of metabolic and electrolyte derangements in resuscitated CA patients. PMID- 26670820 TI - Post-cardiac arrest extracorporeal life support. AB - Sudden cardiac arrest is a complex, life-threatening event involving a multidisciplinary approach. Despite the use of conventional cardiopulmonary resuscitation, survival rate continues to be low for both in-hospital and out-of hospital cardiac arrest. In refractory cardiac arrest, defined by the absence of return of spontaneous circulation despite resuscitation manoeuvres, mortality approaches 100%. In the last years, an increasing number of case series, and few propensity-matched cohort studies have reported encouraging results on the use of venoarterial extracorporeal membrane oxygenation for refractory cardiac arrest. Extracorporeal circulation ensures an adequate blood flow, to perform diagnostic and therapeutic interventions even before a return of spontaneous circulation is achieved and to rest the heart by unloading the ventricle while ensuring myocardial perfusion after return of spontaneous circulation. This study reviews the rational, indications, evidence and management of extracorporeal support for cardiac arrest. PMID- 26670819 TI - The optimal hemodynamics management of post-cardiac arrest shock. AB - Patients resuscitated from cardiac arrest develop a pathophysiological state named "post-cardiac arrest syndrome." Post-resuscitation myocardial dysfunction is a common feature of this syndrome, and many patients eventually die from cardiovascular failure. Cardiogenic shock accounts for most deaths in the first 3 days, when post-resuscitation myocardial dysfunction peaks. Thus, identification and treatment of cardiovascular failure is one of the key therapeutic goals during hospitalization of post-cardiac arrest patients. Patients with hemodynamic instability may require advanced cardiac output monitoring. Inotropes and vasopressors should be considered if hemodynamic goals are not achieved despite optimized preload. If these measures fail to restore adequate organ perfusion, a mechanical circulatory assistance device may be considered. Adequate organ perfusion should be ensured in the absence of definitive data on the optimal target pressure goals. Hemodynamic goals should also take into account targeted temperature management and its effect on the cardiovascular function. PMID- 26670821 TI - Self-Assembled 3D Foam-Like NiCo2O4 as Efficient Catalyst for Lithium Oxygen Batteries. AB - A self-assembled 3D foam-like NiCo2O4 catalyst has been synthesized via a simple and environmental friendly approach, wherein starch acts as the template to form the unique 3D architecture. Interestingly, when employed as a cathode for lithium oxygen batteries, it demonstrates superior bifunctional electrocatalytic activities toward both the oxygen reduction reaction and the oxygen evolution reaction, with a relatively high round-trip efficiency of 70% and high discharge capacity of 10 137 mAh g(-1) at a current density of 200 mA g(-1), which is much higher than those in previously reported results. Meanwhile, rotating disk electrode measurements in both aqueous and nonaqueous electrolyte are also employed to confirm the electrocatalytic activity for the first time. This excellent performance is attributed to the synergistic benefits of the unique 3D foam-like structure and the intrinsically high catalytic activity of NiCo2O4 . PMID- 26670822 TI - Are variations in heterotrophic soil respiration related to changes in substrate availability and microbial biomass carbon in the subtropical forests? AB - Soil temperature and moisture are widely-recognized controlling factors on heterotrophic soil respiration (Rh), although they often explain only a portion of Rh variability. How other soil physicochemical and microbial properties may contribute to Rh variability has been less studied. We conducted field measurements on Rh half-monthly and associated soil properties monthly for two years in four subtropical forests of southern China to assess influences of carbon availability and microbial properties on Rh. Rh in coniferous forest was significantly lower than that in the other three broadleaf species-dominated forests and exhibited obvious seasonal variations in the four forests (P < 0.05). Temperature was the primary factor influencing the seasonal variability of Rh while moisture was not in these humid subtropical forests. The quantity and decomposability of dissolved organic carbon (DOC) were significantly important to Rh variations, but the effect of DOC content on Rh was confounded with temperature, as revealed by partial mantel test. Microbial biomass carbon (MBC) was significantly related to Rh variations across forests during the warm season (P = 0.043). Our results suggest that DOC and MBC may be important when predicting Rh under some conditions, and highlight the complexity by mutual effects of them with environmental factors on Rh variations. PMID- 26670823 TI - Group cognitive behavioural treatment for insomnia in primary care: a randomized controlled trial. AB - BACKGROUND: Insomnia disorder is common and often co-morbid with mental health conditions. Cognitive behavioural therapy (CBT) for insomnia is effective, but is rarely implemented as a discrete treatment. The aim of this study was to evaluate the effectiveness of brief CBT groups for insomnia compared to treatment as usual (TAU) for insomnia delivered by mental health practitioners in a primary-care mental health service. METHOD: A total of 239 participants were randomized to either a five-session CBT group or to TAU. Assessments of sleep and of symptoms of depression and anxiety were carried out at baseline, post-treatment and at 20 weeks. Primary outcome was sleep efficiency post-treatment. RESULTS: Group CBT participants had better sleep outcomes post-treatment than those receiving TAU [sleep efficiency standardized mean difference 0.63, 95% confidence interval (CI) 0.34-0.92]. The effect at 20 weeks was smaller with a wide confidence interval (0.27, 95% CI -0.03 to 0.56). There were no important differences between groups at either follow-up period in symptoms of anxiety or depression. CONCLUSIONS: Dedicated CBT group treatment for insomnia improves sleep more than treating sleep as an adjunct to other mental health treatment. PMID- 26670824 TI - Autophagy postpones apoptotic cell death in PRRSV infection through Bad-Beclin1 interaction. AB - Autophagy and apoptosis play significant roles in PRRSV infection and replication. However, the interaction between these 2 processes in PRRSV replication is still far from been completely understood. In our studies, the exposure of MARC-145 cells to PRRSV confirmed the activation of autophagy and subsequent induction of apoptosis. The inhibition of autophagy by 3-methyladenine (3-MA) caused a significant increase in PRRSV-induced apoptosis, showing a potential connection between both mechanisms. Moreover, we observed an increase in Bad expression (a pro-apoptotic protein) and Beclin1 (an autophagy regulator) in virus-infected cells up to 36h. Co-immunoprecipitation assays showed the formation of Bad and Beclin1 complex in PRRSV infected cells. Accordingly, Bad co localized with Beclin1 in MARC-145 infected cells. Knockdown of Beclin1 significantly decreased PRRSV replication and PRRSV-induced autophagy, while Bad silencing resulted in increased autophagy and enhanced viral replication. Furthermore, PRRSV infection phosphorylated Bad (Ser112) to promote cellular survival. These results demonstrate that autophagy can favor PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin1 complex. PMID- 26670826 TI - BIBF1120 (Vargatef) Inhibits Preretinal Neovascularization and Enhances Normal Vascularization in a Model of Vasoproliferative Retinopathy. AB - PURPOSE: This study evaluated the effects of BIBF1120, a novel triple angiokinase inhibitor against pathological retinal neovascularization. METHODS: BIBF1120 effect on development of the normal retinal vasculature was evaluated in Sprague Dawley rat pups. Two models of ischemic oxygen-induced retinopathy (OIR) and the aortic ring assay were used to assess the antiangiogenic effects of BIBF1120. In the vaso-obliteration model (VO), rat pups were exposed to 80% O2 from postnatal day (P) 5 to P10. In the preretinal neovascularization (NV) model, rat pups were exposed to cycling O2 (50% and 10%) from P1 to P14, followed by room air until P18. Animals were intravitreally or orally treated with BIBF1120. Retinal vasculature, VO, and NV were evaluated in retinal flat mounts. Retinal expression of VEGF, Delta-like ligand 4 (Dll4), Netrin-1, Ephrin-B2, and EphB4 was analyzed by quantitative PCR and Western blot analysis. RESULTS: BIBF1120 interfered with normal retinal vascular development and microvessel branching in the aortic assay. However, in VO model BIBF1120 did not accrue VO. On the contrary, in the NV model BIBF1120 accelerated normal retinal vascularization and robustly diminished preretinal neovascularization compared to vehicle (by ~80%). The expression levels of VEGF negative regulator Dll4 and repulsive cues EphrinB2 and EphB4 mRNA in the retina of vehicle-treated OIR animals were markedly increased compared to normoxia, but were normalized by BIBF1120. CONCLUSIONS: Data reveal efficacy of BIBF1120 on preretinal neovascularization and, of greater interest, on acceleration of normal vascularization, consistent with interference of major repulsive cues expressed in the retina during OIR. Accordingly, BIBF1120 appears to exhibit preferable properties compared to anti-VEGF therapies for the treatment of ischemic retinopathies. PMID- 26670825 TI - Corneal Expression of SLURP-1 by Age, Sex, Genetic Strain, and Ocular Surface Health. AB - PURPOSE: Although secreted Ly6/urokinase-type plasminogen activator receptor related protein-1 (Slurp1) transcript is highly abundant in the mouse cornea, corresponding protein expression remains uncharacterized. Also, SLURP1 was undetected in previous tear proteomics studies, resulting in ambiguity about its baseline levels. Here, we examine mouse corneal Slurp1 expression in different sexes, age groups, strains, and health conditions, and quantify SLURP1 in human tears from healthy or inflamed ocular surfaces. METHODS: Expression of Slurp1 in embryonic day-13 (E13), E16, postnatal day-1 (PN1), PN10, PN20, and PN70 Balb/C, FVBN, C57Bl/6, and DBA/2J mouse corneas, Klf4Delta/DeltaCE corneas with corneal epithelial-specific ablation of Klf4, migrating cells in wild-type corneal epithelial wound edge, and in corneas exposed to pathogen-associated molecular patterns (PAMPs) poly(I:C), zymosan-A, or Pam3Csk4 was examined by QPCR, immunoblots, and immunofluorescent staining. Human SLURP1 levels were quantified by ELISA in tears from 34 men and women aged 18 to 80 years. RESULTS: Expression of Slurp1, comparable in different strains and sexes, was low in E13, E16, PN1, and PN10 mouse corneas, and increased rapidly after eyelid opening in a Klf4 dependent manner. We found Slurp1 was downregulated in corneas exposed to PAMPs, and in migrating cells at the wound edge. Human SLURP1 expression, comparable in different sexes and age groups, was significantly decreased in tears from inflamed ocular surfaces (0.34%) than those from healthy individuals (0.77%). CONCLUSIONS: These data describe the influence of age, sex, genetic background, and ocular surface health on mouse corneal expression of Slurp1, establish the baseline for human tear SLURP1 expression, and identify SLURP1 as a useful diagnostic and/or therapeutic target for inflammatory ocular surface disorders. PMID- 26670827 TI - A Comparison of Different Corneal Iontophoresis Protocols for Promoting Transepithelial Riboflavin Penetration. AB - PURPOSE: To measure corneal riboflavin penetration using different transepithelial iontophoresis protocols. METHODS: Freshly enucleated rabbit eyes were divided into nine treatment groups of 4 eyes. One group, in which 0.1% wt/vol riboflavin was applied for 30 minutes without iontophoresis after corneal epithelial debridement, acted as a control. The remaining groups were treated with an intact epithelium using different riboflavin formulations and varying iontophoresis current, soak, and rinse times. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35 MUm thick were then imaged immediately by two-photon fluorescence microscopy, using image processing software to quantify stromal riboflavin concentration at different corneal depths. RESULTS: In the epithelium-on iontophoresis treatment groups, greater stromal riboflavin penetration was achieved with higher-concentration riboflavin solutions, greater iontophoresis dosage, and longer solution contact times. A protocol utilizing 0.25% wt/vol riboflavin with benzalkonium chloride (BAC) 0.01% and two cycles of applied current and subsequent soaking (1 mA 5 minutes, soak 5 minutes; 0.5 mA 5 minutes, soak 5 minutes) achieved similar stromal riboflavin penetration to epithelium-off controls. The best-performing non-BAC-containing protocol produced stromal riboflavin penetration approximately 60% that of epithelium-off controls. Riboflavin solutions containing saline resulted in minimal stromal penetration. Riboflavin loading within the epithelium was equivalent to or higher than that in the subjacent stroma, despite rinsing the ocular surface with balanced salt solution. CONCLUSIONS: Modified iontophoresis protocols can significantly improve transepithelial riboflavin penetration in experimental corneal collagen cross-linking. PMID- 26670828 TI - Diagnostic Ability of Retinal Vessel Diameter Measurements in Open-Angle Glaucoma. AB - PURPOSE: To determine the diagnostic ability of retinal vessel diameter (RVD) measurements and the factors related to retinal vascular diameters in patients with open-angle glaucoma (OAG). METHODS: This retrospective observational study included 145 patients with OAG (63 with high-tension and 82 with low-tension glaucoma) and 60 healthy controls. The central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured using the IVAN software version 1.3. Receiver operating characteristic (ROC) curves were obtained for the average retinal nerve fiber layer (RNFL) thickness and RVD indices including CRAE, CRVE, and CRAE/CRVE ratio. Areas under the ROC curves (AUCs), 95% confidence intervals (CIs), and sensitivities at a fixed specificity (>90% and >80%) were calculated. Factors related to CRAE were analyzed by simple and multiple linear regression analyses. RESULTS: Among the RVD indices, the CRAE had the largest AUC for discriminating glaucomatous changes between eyes with glaucoma and those without (0.803; 95% CI, 0.742-0.855). The AUC of CRAE did not significantly differ from that of average RNFL thickness (P = 0.134). However, CRAE showed lower sensitivity than average RNFL thickness at a specificity greater than 90%. Factors significantly associated with CRAE in both simple and multiple linear regression analyses were age, spherical equivalent, average RNFL thickness, presence of diabetes mellitus, and a glaucoma diagnosis (all P <= 0.05). CONCLUSIONS: The diagnostic ability of CRAE for detecting OAG was good, which was not much worse than that of average RNFL thickness. This finding suggests the potential usefulness of RVD for glaucoma detection. PMID- 26670829 TI - Mouse Models for the Dissection of CHD7 Functions in Eye Development and the Molecular Basis for Ocular Defects in CHARGE Syndrome. AB - PURPOSE: CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary tract abnormalities, and Ear abnormalities and deafness) is the second-leading cause of deaf-blindness after Usher syndrome. Heterozygous mutations in CHD7 cause CHARGE syndrome in 70% to 90% of patients. We tested the hypothesis that tissue-specific mutant mice provide models for molecularly dissecting CHD7 functions during eye development. METHODS: The conditional Chd7flox allele was mated together with tissue-specific Cre transgenes. Immunohistochemistry was used to determine the normal CHD7 pattern in the early eye primordia and to assess Chd7 mutants for expression of region-specific protein markers. RESULTS: CHD7 is present in the neural ectoderm and surface ectoderm of the eye. Deletion from neural and surface ectoderm results in severely dysmorphic eyes generally lacking recognizable optic cup structures and small lenses. Deletion from the neural ectoderm results in similar defects. Deletion from the surface ectoderm results in eyes with smaller lenses. Lens tissue and the major subdivisions of the neural ectoderm are present following conditional deletion of Chd7 from the neural ectoderm. Closure of the optic fissure depends on the Chd7 gene dose within the neural ectoderm. CONCLUSIONS: Eye development requires CHD7 in multiple embryonic tissues. Lens development requires CHD7 in the surface ectoderm, whereas optic cup and stalk morphogenesis require CHD7 in the neural ectoderm. CHD7 is not absolutely required for specification of the major subdivisions within the neural ectoderm. As in humans, normal eye development in mice is sensitive to Chd7 haploinsufficiency. These data indicate the Chd7 mutant mice are models for determining the molecular etiology of ocular defects in CHARGE syndrome. PMID- 26670831 TI - Exchange Transfusion and Leukapheresis in Pediatric Patients with AML With High Risk of Early Death by Bleeding and Leukostasis. AB - BACKGROUND: The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/MUl). Within the pediatric AML BFM (Berlin-Frankfurt-Munster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed. PATIENTS: Two hundred thirty eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis. RESULTS: ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/MUl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American British) M4/M5 and hyperleukocytosis >200,000/MUl. Patients with WBC >200,000/MUl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/MUl was of strongest prognostic significance for ED (P(chi(2) ) <0.0001). CONCLUSION: Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. ET/LPh shows a trend toward reduced ED rate due to bleeding/leukostasis and is recommended at WBC >200,000/MUl, and in FAB M4/M5 even at lower WBC. PMID- 26670830 TI - Measuring In Vivo Free Radical Production by the Outer Retina. AB - PURPOSE: Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-MUm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). METHODS: Low-dose sodium iodate treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl-/- mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and alpha-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). RESULTS: In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2 month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. CONCLUSIONS: Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo. PMID- 26670832 TI - Surgical Treatment of Uterine Fibroids Within a Containment System and Without Power Morcellation. AB - Increased awareness regarding risks associated with intracorporeal electromechanical, or power, morcellation has urged surgeons to develop alternative methods for tissue extraction that may mitigate some of these risks during surgery. The use of containment systems during laparoscopic procedures has allowed surgeons to continue to offer and perform myomectomies that still benefit from being minimally invasive but which may minimize the risk of inadvertent tissue dispersion. Here, we will review techniques for performing contained tissue fragmentation without the use of a power morcellator. PMID- 26670833 TI - Are Women With Uterine Fibroids at Increased Risk for Adverse Pregnancy Outcome? AB - Uterine fibroids (leiomyomas) are common in reproductive age women. Most women with fibroids have uneventful pregnancies. The most common complication is painful degeneration. Are fibroids associated with adverse pregnancy outcomes? If so, can we predict which fibroids are most likely to cause complications? And is there anything that can be done to prevent these complications, such as performing a myomectomy before pregnancy? Here we review the published literature looking at the impact of uterine fibroids on adverse pregnancy events, such as miscarriage, preterm labor, placental abruption, fetal growth restriction, and fetal malpresentation. A series of clinical recommendations for the management of pregnancy in women with uterine fibroids are included. PMID- 26670834 TI - What is the Future of Open Intraperitoneal Power-Morcellation of Fibroids? AB - In November 2014, the Food and Drug Administration (FDA) calculated that for every 498 women having surgery for presumed fibroids, one woman would be found to have an occult leiomyosarcoma (LMS). The FDA issued a safety communication warning against the use of laparoscopic morcellators in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids. This communication was prompted by concern that if a patient had an occult LMS, the morcellator might spread tumor cells within the peritoneal cavity. We submit that the FDA directive was based on a flawed and misleading analysis. More rigorous evidence estimates the prevalence of LMS among women operated upon for presumed uterine fibroids at approximately one in 2000 women, significantly lower than the FDA's estimate. In addition, there is no reliable evidence that morcellation influences survival or that power-morcellation is inferior to vaginal or mini-lap morcellation with a scalpel. Recent publication shows that open surgery carries more risk for women when compared with minimally invasive surgery. Although the possibility of occult LMS should be considered by women and their gynecologists, we suggest that current morcellation techniques be continued for women who wish to benefit from minimally invasive surgery. Investigation into new and, hopefully, better morcellating devices may make the procedure safer for women. PMID- 26670835 TI - Genetic Screening and the Obese Gravida. AB - Obesity compromises all forms of genetic screening. Although the risk for fetal aneuploidy is not altered by obesity, the risk for significant birth defects is increased. Therefore, the obese gravida is at an increased risk of fetal malformations with a diminished ability to be screened effectively by all screening methods: ultrasound, traditional serum analyte screening, and cell-free DNA screening. This chapter outlines both the current options and limitations of screening in the obese gravida. The offering of screening and diagnostic testing should not be altered in obese women despite the compromises placed on accurate fetal assessment. PMID- 26670837 TI - Laparoscopic Hysterectomy for Uterine Fibroids: Is it Safe? AB - As more complex cases and larger uterine specimens are able to be managed with minimally invasive surgery, the limitations of tissue retrieval with these methods are of increasing concern. Risks of morcellator-related injury, tissue dissemination, or fragmentation must be weighed against increased morbidity of abdominal approach to hysterectomy. In an effort to mitigate the risks of tissue morcellation, containment system use must be considered when fragmenting a specimen, either with power morcellation or a manual technique via the vagina or minilaparotomy. PMID- 26670838 TI - Corrigendum. PMID- 26670839 TI - The generation of stationary pi-electron rotations in chiral aromatic ring molecules possessing non-degenerate excited states. AB - The electron angular momentum is a fundamental quantity of high-symmetry aromatic ring molecules and finds many applications in chemistry such as molecular spectroscopy. The stationary angular momentum or unidirectional rotation of pi electrons is generated by the excitation of a degenerated electronic excited state by a circularly-polarized photon. For low-symmetry aromatic ring molecules having non-degenerate states, such as chiral aromatic ring molecules, on the other hand, whether stationary angular momentum can be generated or not is uncertain and has not been clarified so far. We have found by both theoretical treatments and quantum optimal control (QOC) simulations that a stationary angular momentum can be generated even from a low-symmetry aromatic ring molecule. The generation mechanism can be explained in terms of the creation of a dressed-state, and the maximum angular momentum is generated by the dressed state with an equal contribution from the relevant two excited states in a simple three electronic state model. The dressed state is formed by inducing selective nonresonant transitions between the ground and each excited state by two lasers with the same frequency but having different polarization directions. The selective excitation can be carried out by arranging each photon-polarization vector orthogonal to the electronic transition moment of the other transition. We have successfully analyzed the results of the QOC simulations of (P)-2,2' biphenol of axial chirality in terms of the analytically determined optimal laser fields. The present findings may open up new types of chemical dynamics and spectroscopy by utilizing strong stationary ring currents and current-induced magnetic fields, which are created at a local site of large compounds such as biomolecules. PMID- 26670840 TI - Ewing Sarcoma: A 15-Year Experience of a Single Center With the MSKCC P6 Treatment Protocol. AB - INTRODUCTION: Ewing sarcoma (ES) is the second most common bone tumor in children. Current chemotherapeutic regimens include high-dose anthracyclines and alkylating agents with significant variation in treatment length. The Memorial Sloan Kettering Cancer Center P6 regimen (MSKCC P6) treatment protocol is a highly aggressive regimen given over 21 weeks only. We present the outcome of ES patients treated in our center with this protocol over the last 15 years. PROCEDURE: We retrospectively analyzed data on the presentation, patient characteristics, treatment, and outcome of all ES patients treated according to the MSKCC P6 regimen from 1999 to 2014. RESULTS: Of 48 patients, 37 (77%) presented with a nonmetastatic disease and 26 (54%) with tumor located in the extremities. The 5-year overall survival (OS) of the entire cohort was 55.9% +/- 8%. Nonmetastatic disease conferred a better prognosis with a 5-year OS of 68.4% +/- 8.5%. Patients with a nonmetastatic extremity tumor had the most favorable outcome with 5-year OS of 72.2% +/- 9.8%. CONCLUSION: The outcome of ES patients after a short aggressive course of chemotherapy (the MSKCC P6 protocol), is comparable to that following other first-line treatment regimens in use, with potentially fewer long-term adverse events. PMID- 26670841 TI - Synthesis, in vitro antitumor activity, dihydrofolate reductase inhibition, DNA intercalation and structure-activity relationship studies of 1,3,5-triazine analogues. AB - A series of triazine-benzimidazoles with 4-fluoroaniline substitution has been designed and synthesized. These compounds were further substituted with different primary and secondary amines. The structures of newly synthesized compounds were confirmed by (1)H, (13)C NMR, mass spectrometry and, in case of compound 18, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumor cell lines at one dose and five dose concentration levels. Compounds 7, 8 and 22 have been found to be the most active antitumor agents with GI50 values of 1.77, 1.94 and 2.87MUM, respectively. The synthesized compounds were then evaluated for their inhibitory activity to mammalian dihydrofolate reductase. Compound 22 was depicted as the most active compound for the inhibition of dihydrofolate reductase with IC50 value of 2.0nM. DNA binding studies were also revealed strong interacting properties of triazine derivatives towards calf thymus-DNA. PMID- 26670842 TI - Anti-tumor activity evaluation of novel chrysin-organotin compound in MCF-7 cells. AB - Chrysin (5,7-dihydroxylflavone, Chry) is a natural flavonoid extracted from plants and propolis. In this work, a novel chrysin-organotin (Chry-Sn) compound with enhanced anticancer activities was synthesized by the reaction of chrysin and triphenyltin chloride, and its potential anticancer effects against cancer cells were measured using various methods. Sulforhodamine B (SRB) results showed that chrysin and Chry-Sn had significant inhibition effects on the proliferation of MCF-7, A549 and HeLa human cancer cell lines in a dose- and time- dependent manner. These results suggested that Chry-Sn possessed enhanced anticancer effects. Hoechst 33258 staining and acridine orange staining results showed apoptosis and nuclei fragments significantly increased after being treated with chrysin and Chry-Sn respectively. Moreover, chrysin and Chry-Sn significantly increased ROS levels in MCF-7 cells. Western blot results showed that chrysin and Chry-Sn activated caspase 3 and induced autophagy by increasing LC3-II level. All results showed collectively that Chry-Sn could be a more promising drug than chrysin in anticancer treatment. PMID- 26670843 TI - Melanoma knowledge, risk factors awareness and skin health behaviours: a populational-based study in Central Romania. PMID- 26670846 TI - Convex array vector velocity imaging using transverse oscillation and its optimization. AB - A method for obtaining vector flow images using the transverse oscillation (TO) approach on a convex array is presented. The paper presents optimization schemes for TO fields and evaluates their performance using simulations and measurements with an experimental scanner. A 3-MHz 192-element convex array probe (pitch 0.33 mm) is used in both simulations and measurements. A parabolic velocity profile is simulated at a beam-to-flow angle of 90 degrees . The optimization routine changes the lateral oscillation period lambda? as a function of depth to yield the best possible estimates based on the energy ratio between positive and negative spatial frequencies in the ultrasound field. The energy ratio is reduced from -17.1 dB to -22.1 dB. Parabolic profiles are estimated on simulated data using 16 emissions. The optimization gives a reduction in standard deviation from 8.81% to 7.4% for 16 emissions, with a reduction in lateral velocity bias from 15.93% to 0.78% at 90 degrees (transverse flow) at a depth of 40 mm. Measurements have been performed using the experimental ultrasound scanner and a convex array transducer. A bias of -0.93% was obtained at 87 degrees for a parabolic velocity profile along with a standard deviation of 6.37%. The livers of two healthy volunteers were scanned using the experimental setup. The in vivo images demonstrate that the method yields realistic estimates with a consistent angle and mean velocity across three heart cycles. PMID- 26670845 TI - In Vivo application and localization of transcranial focused ultrasound using dual-mode ultrasound arrays. AB - Focused ultrasound (FUS) has been proposed for a variety of transcranial applications, including neuromodulation, tumor ablation, and blood-brain barrier opening. A flurry of activity in recent years has generated encouraging results demonstrating its feasibility in these and other applications. To date, monitoring of FUS beams has been primarily accomplished using MR guidance, where both MR thermography and elastography have been used. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm in transcranial focusing. In this paper, we present first experimental results of ultrasound-guided transcranial FUS (tFUS) application in a rodent brain, both ex vivo and in vivo. DMUA imaging is used for visualization of the treatment region for placement of the focal spot within the brain. This includes the detection and localization of pulsating blood vessels at or near the target point(s). In addition, DMUA imaging is used to monitor and localize the FUS-tissue interactions in real time. In particular, a concave (40 mm radius of curvature), 32-element, 3.5-MHz DMUA prototype was used for imaging and tFUS application in ex vivo and in vivo rat models. The ex vivo experiments were used to evaluate the point spread function of the transcranial DMUA imaging at various points within the brain. In addition, DMUA-based transcranial ultrasound thermography measurements were compared with thermocouple measurements of subtherapeutic tFUS heating in rat brain ex vivo. The ex vivo setting was also used to demonstrate the capability of DMUA to produce localized thermal lesions. The in vivo experiments were designed to demonstrate the ability of the DMUA to apply, monitor, and localize subtherapeutic tFUS patterns that could be beneficial in transient blood-brain barrier opening. The results show that although the DMUA focus is degraded due to the propagation through the skull, it still produces localized heating effects within a sub-millimeter volume. In addition, DMUA transcranial echo data from brain tissue allow for reliable estimation of temperature change. PMID- 26670847 TI - Shear wave arrival time estimates correlate with local speckle pattern. AB - We present simulation and phantom studies demonstrating a strong correlation between errors in shear wave arrival time estimates and the lateral position of the local speckle pattern in targets with fully developed speckle. We hypothesize that the observed arrival time variations are largely due to the underlying speckle pattern, and call the effect speckle bias. Arrival time estimation is a key step in quantitative shear wave elastography, performed by tracking tissue motion via cross-correlation of RF ultrasound echoes or similar methods. Variations in scatterer strength and interference of echoes from scatterers within the tracking beam result in an echo that does not necessarily describe the average motion within the beam, but one favoring areas of constructive interference and strong scattering. A swept-receive image, formed by fixing the transmit beam and sweeping the receive aperture over the region of interest, is used to estimate the local speckle pattern. Metrics for the lateral position of the speckle are found to correlate strongly (r > 0.7) with the estimated shear wave arrival times both in simulations and in phantoms. Lateral weighting of the swept-receive pattern improved the correlation between arrival time estimates and speckle position. The simulations indicate that high RF echo correlation does not equate to an accurate shear wave arrival time estimate-a high correlation coefficient indicates that motion is being tracked with high precision, but the location tracked is uncertain within the tracking beam width. The presence of a strong on-axis speckle is seen to imply high RF correlation and low bias. The converse does not appear to be true-highly correlated RF echoes can still produce biased arrival time estimates. The shear wave arrival time bias is relatively stable with variations in shear wave amplitude and sign (-20 MUm to 20 MUm simulated) compared with the variation with different speckle realizations obtained along a given tracking vector. We show that the arrival time bias is weakly dependent on shear wave amplitude compared with the variation with axial position/ local speckle pattern. Apertures of f/3 to f/8 on transmit and f/2 and f/4 on receive were simulated. Arrival time error and correlation with speckle pattern are most strongly determined by the receive aperture. PMID- 26670848 TI - Removal of residual cavitation nuclei to enhance histotripsy fractionation of soft tissue. AB - Remanent bubble nuclei generated by primary cavitation collapse can limit the efficiency of histotripsy softtissue fractionation. When these residual bubbles persist from one histotripsy pulse to the next, they can seed the repetitive nucleation of cavitation bubbles at a discrete set of sites within the focal volume. This effect-referred to as cavitation memory- manifests in inefficient lesion formation, because certain sites within the focal volume are overtreated whereas others remain undertreated. Although the cavitation memory effect can be passively mitigated by using a low pulse repetition frequency (PRF) that affords remanent nuclei sufficient time for dissolution between successive pulses, this low PRF also results in slow lesion production. As such, it would be highly desirable to maintain the high per-pulse efficiency associated with low pulse rates when much higher PRFs are utilized. In this vein, we have developed a strategy for the active removal of the remanent bubble nuclei following primary cavitation collapse, using low-amplitude ultrasound sequences (termed bubble removal sequences) to stimulate the aggregation and subsequent coalescence of these bubbles. In this study, bubbleremoval sequences were incorporated in high PRF histotripsy treatment (100 Hz) of a red blood cell tissue-mimicking phantom that allows for the visualization of lesion development in real time. A series of reference treatments were also conducted at the low PRF of 1 Hz to provide a point of comparison for which cavitation memory effects are minimal. It was found that bubble-removal sequences as short as 1 ms are capable of maintaining the efficacious lesion development characteristics associated with the low PRF of 1 Hz when the much higher pulse rate of 100 Hz is used. These results were then extended to the treatment of a large volume within the tissue phantom, and optimal bubble-removal sequences identified for the singlefocal- spot case were utilized to homogenize a 10 * 10 mm region at high rate. PMID- 26670849 TI - Clutter filtering influence on blood velocity estimation using speckle tracking. AB - Blood speckle tracking has shown potential for solving the angle-dependency limitation in color flow imaging. However, as clutter filtering is still Doppler based, flow velocities at near-perpendicular beam-to-flow angles can be severely attenuated. It is shown that the clutter filter also alters the speckle appearance through a decrease in the lateral imaging bandwidth, leading to poorer lateral resolution and thus tracking performance. Interestingly, at perpendicular beam-to-flow angles lateral band-pass characteristics are inferred, and the resulting lateral amplitude modulation could help improve tracking estimates. Simulations and flow phantom experiments showed that substantially improved results could be achieved by utilizing time-variant clutter filters (e.g., polynomial regression filters) despite the inherent decorrelation inferred by these filters, but only for higher ensemble sizes (N > 36). We found that, compared with color flow imaging, speckle tracking could yield consistent estimates well below the clutter filter cutoff, but with a higher variance attributed to the low signalto- noise ratio inferred by filter attenuation. Overall, provided that a low f-number and high ensemble lengths (N approx. > 36) can be used, speckle tracking can consistently provide angle- independent flow velocity estimates, limited only by a lower bound on the flow velocity itself. PMID- 26670851 TI - A new method for shear wave speed estimation in shear wave elastography. AB - Visualization of mechanical properties of tissue can aid in noninvasive pathology diagnosis. Shear wave elastography (SWE) measures the elastic properties of soft tissues by estimation of local shear wave propagation speed. In this paper, a new robust method for estimation of shear wave speed is introduced which has the potential for simplifying continuous filtering and real-time elasticity processing. Shear waves were generated by external mechanical excitation and imaged at a high frame rate. Three homogeneous phantoms of varying elastic moduli and one inclusion phantom were imaged. Waves propagating in separate directions were filtered and shear wave speed was estimated by inversion of the 1-D first order wave equation. Final 2-D shear wave speed maps were constructed by weighted averaging of estimates from opposite traveling directions. Shear wave speed results for phantoms with gelatin concentrations of 5%, 7%, and 9% were 1.52 +/- 0.10 m/s, 1.86 +/- 0.10 m/s, and 2.37 +/- 0.15 m/s, respectively, which were consistent with estimates computed from three other conventional methods, as well as compression tests done with a commercial texture analyzer. The method was shown to be able to reconstruct a 2-D speed map of an inclusion phantom with good image quality and variance comparable to conventional methods. Suggestions for further work are given. PMID- 26670850 TI - Noninvasive thrombolysis using microtripsy: a parameter study. AB - Histotripsy fractionates soft tissue by well-controlled acoustic cavitation using microsecond-long, high-intensity ultrasound pulses. The feasibility of using histotripsy as a noninvasive, drug-free, and image-guided thrombolysis method has been shown previously. A new histotripsy approach, termed microtripsy, has recently been investigated for the thrombolysis application to improve treatment accuracy and avoid potential vessel damage. In this study, we investigated the effects of pulse repetition frequency (PRF) on microtripsy thrombolysis. Microtripsy thrombolysis treatments using different PRFs (5, 50, and 100 Hz) and doses (20, 50, and 100 pulses) were performed on blood clots in an in vitro vessel flow model. To quantitatively evaluate the microtripsy thrombolysis effect, the location of focal cavitation, the incident rate of pre-focal cavitation on the vessel wall, the size and location of the resulting flow channel, and the generated clot debris particles were measured. The results demonstrated that focal cavitation was always well confined in the vessel lumen without contacting the vessel wall for all PRFs. Pre-focal cavitation on the front vessel wall was never observed at 5Hz PRF, but occasionally observed at PRFs of 50 Hz (1.2%) and 100 Hz (5.4%). However, the observed pre-focal cavitation was weak and did not significantly affect the focal cavitation. Results further demonstrated that, although the extent of clot fractionation per pulse was the highest at 5 Hz PRF at the beginning of treatment (<20 pulses), 100 Hz PRF generated the largest flow channels with a much shorter treatment time. Finally, results showed fewer large debris particles were generated at a higher PRF. Overall, the results of this study suggest that a higher PRF (50 or 100 Hz) may be a better choice for microtripsy thrombolysis to use clinically due to the larger resulting flow channel, shorter treatment time, and smaller debris particles. PMID- 26670852 TI - Plane-wave transverse oscillation for high-frame-rate 2-D vector flow imaging. AB - Transverse oscillation (TO) methods introduce oscillations in the pulse-echo field (PEF) along the direction transverse to the ultrasound propagation direction. This may be exploited to extend flow investigations toward multidimensional estimates. In this paper, the TOs are coupled with the transmission of plane waves (PWs) to reconstruct high-framerate RF images with bidirectional oscillations in the pulse-echo field. Such RF images are then processed by a 2-D phase-based displacement estimator to produce 2-D vector flow maps at thousands of frames per second. First, the capability of generating TOs after PW transmissions was thoroughly investigated by varying the lateral wavelength, the burst length, and the transmission frequency. Over the entire region of interest, the generated lateral wavelengths, compared with the designed ones, presented bias and standard deviation of -3.3 +/- 5.7% and 10.6 +/- 7.4% in simulations and experiments, respectively. The performance of the ultrafast vector flow mapping method was also assessed by evaluating the differences between the estimated velocities and the expected ones. Both simulations and experiments show overall biases lower than 20% when varying the beam-to-flow angle, the peak velocity, and the depth of interest. In vivo applications of the method on the common carotid and the brachial arteries are also presented. PMID- 26670853 TI - Comparison between shear wave dispersion magneto motive ultrasound and transient elastography for measuring tissue-mimicking phantom viscoelasticity. AB - Several methods have been developed over the last several years to analyze the mechanical properties of soft tissue. Elastography, for example, was proposed to evaluate soft tissue stiffness in an attempt to reduce the need for invasive procedures, such as breast biopsies; however, its qualitative nature and the fact that it is operator-dependent have proven to be limitations of the technique. Quantitative shearwave- based techniques have been proposed to obtain information about tissue stiffness independent of the operator. This paper describes shear wave dispersion magnetomotive ultrasound (SDMMUS), a new shear-wave-based method in which a viscoelastic medium labeled with iron oxide nanoparticles is displaced by an external tone burst magnetic field. As in magnetomotive ultrasound (MMUS), SDMMUS uses ultrasound to detect internal mechanical vibrations induced by the interaction between a magnetic field and magnetic nanoparticles. These vibrations generated shear waves that were evaluated to estimate the viscoelastic properties of tissue-mimicking phantoms. These phantoms were manufactured with different concentrations of gelatin and labeled with iron oxide nanoparticles. The elasticity and viscosity obtained with SDMMUS agreed well with the results obtained by traditional ultrasound-based transient elastography. PMID- 26670854 TI - Characterization of defects using ultrasonic arrays: a dynamic classifier approach. AB - In the field of nondestructive evaluation, accurate characterization of defects is required for the assessment of defect severity. Defect characterization is studied in this paper through the use of the ultrasonic scattering matrix, which can be extracted from the array measurements. Defects that have different shapes are classified into different defect classes, and this essentially allows us to distinguish between crack-like defects and volumetric voids. Principal component analysis (PCA) is used for feature extraction, and several representational principal component subsets are found through exhaustive searching in which quadratic discriminant analysis (QDA) and support vector machine (SVM) are used as the pattern classifiers. Instead of choosing a single optimal classifier, the best classifier is dynamically selected for different measurements by estimating the local classifier accuracy. The proposed approach is validated in simulation and experiments. In simulation, the depths (lengths of the minor axes) of 4441 out of 4636 test samples are measured accurately, and the measurement errors (with respect to the defect size) are below 10%. Arbitrarily shaped rough volumetric defects are identified as ellipses, which are reasonably good matches in shape to the original defects. Experimentally, six subwavelength scatterers are characterized and sized to within 0.14lambda. PMID- 26670855 TI - Two-dimensional noncontact transportation of small objects in air using flexural vibration of a plate. AB - This paper investigates a two-dimensional ultrasonic manipulation technique for small objects in air. The ultrasonic levitation system consists of a rectangular vibrating plate with four ultrasonic transducers and a reflector. The configuration of the vibrator, the resonant frequency, and the positions of the four transducers with step horns were determined from finite element analysis such that an intense acoustic standing-wave field could be generated between the plates. A lattice flexural vibration mode with a wavelength of 28.3 mm was excited on the prototype plate at 24.6 kHz. Small objects could get trapped in air along the horizontal nodal plane of the standing wave. By controlling the driving phase difference between the transducers, trapped objects could be transported without contact in a two-dimensional plane. When the phase difference was changed from 0 degrees to 720 degrees , the distance moved by a small particle in the orthogonal direction was approximately 29 mm, which corresponds with the wavelength of the flexural vibration on the vibrating plate. PMID- 26670856 TI - Ultrasonic motors with polymer-based vibrators. AB - With their characteristics of low density and elastic moduli, polymers are promising materials for making ultrasonic motors (USMs) with high energy density. Although it has been believed for a long time that polymers are too lossy to be applied to high-amplitude vibrators, there are several new polymers that exhibit excellent vibration characteristics. First, we measure the damping coefficients of some functional polymers to explore the applicability of polymers as vibrators for USMs. Second, to investigate the vibration characteristics, we fabricate bimorph vibrators using several kinds of polymers that have low attenuation. Third, a bending mode USM is fabricated with a polymer rod and four piezoelectric plates bonded on the rod as a typical example of a USM. Through an experimental investigation of the motor performance, it was found that the polymer-based USMs exhibited higher rotation velocity than the aluminum-based USM under a light preload, although the maximum torque of the polymer-based USMs was smaller than the aluminum-based USM. Among the tested polymers, polyphenylenesulfide was a prospective material for USMs under light preloads because of the high amplitude and lightweight of polyphenylenesulfide. PMID- 26670857 TI - eyeless/Pax6 controls the production of glial cells in the visual center of Drosophila melanogaster. AB - Pax6 is known as a neurogenic factor in the development of the central nervous system and regulates proliferation of neuronal progenitor cells and promotes neuronal differentiation. In addition to neurogenesis, Pax6 is also involved in the specification and maturation of glial cells. Here, we show that Eyeless (Ey), Drosophila homolog of Pax6, regulates the production of glial cells in the brain. In the developing fly visual center, the production of neurons and glial cells are controlled by the temporal transcription factors that are sequentially expressed in neuroblasts (NBs). Among them, NBs of the last temporal window produce astrocyte-like glial cells. Ey is strongly expressed in the middle aged NBs, whose temporal window is earlier compared with glia producing older NBs. Weak Ey expression is also detected in the glia producing NBs. Our results suggest that Ey expression in the middle aged NBs indirectly control gliogenesis from the oldest NBs by regulating other temporal transcription factors. Additionally, weak Ey expression in the NBs of last temporal window may directly control gliogenesis. Ey is also expressed in neurons produced from the NBs of Ey positive temporal window. Interestingly, neuron-specific overexpression of Ey causes significant increase in glial cells suggesting that neuronal expression of Ey may also contribute to gliogenesis. Thus, Pax6-dependent regulation of astrocyte-like glial development is conserved throughout the animal kingdom. PMID- 26670858 TI - In Reply. PMID- 26670859 TI - [Spur cell anemia]. PMID- 26670860 TI - Absence of cystatin C involvement in ventricular remodelling and heart failure. AB - Cystatin C (CysC) is a protease encoded by housekeeping genes. Although its prognostic value in heart failure (HF) is well known, it is debatable whether this value is due to the greater accuracy of CysC in calculating the glomerular filtration rate or to its involvement in pathological ventricular remodelling. The aim of this study was to determine whether CysC expression changes in the myocardium of foetuses of different ages and in the myocardium of adults with various cardiovascular diseases, as well as to analyse the correlation between its serum concentrations and cardiac structure and morphology in a patient group with HF. PATIENTS AND METHODS: We analysed the correlations (Pearson's r and Spearman's test) between the serum CysC levels and echocardiographic parameters of 351 patients with HF. We also performed immunohistochemical staining for CysC, metalloproteinase-9 (MMP-9) and desmin in 9 cardiac tissue samples from autopsies of 4 foetuses of different gestational ages and 5 healthy adults or adults with cardiovascular disease. RESULTS: For the patients with HF, there was no correlation between the CysC concentrations and the cardiac parameters measured by 2D echocardiography. The immunohistochemistry showed a weak background staining for CysC in all samples, regardless of age and the presence or absence of cardiovascular diseases. CONCLUSIONS: Our results suggest that CysC does not have a significant role in the pathological remodelling of the left ventricle in HF. PMID- 26670861 TI - New roles in pharmacy - learning from the All Wales Common Ailments Scheme. AB - OBJECTIVES: The objective of this study was to explore the perceptions of stakeholders on a national pilot of a new service, the 'Choose Pharmacy' Common Ailments Service (CAS) in Wales. METHODS: Methods used were semi-structured interviews with stakeholders involved in development and delivery of the CAS. Snowball sampling was employed and invites were extended to eight of 13 pharmacies offering CAS in Cwm Taf LHB, the practice managers at two associated general practitioner surgeries and two local and national level commissioners. KEY FINDINGS: The benefits of encouraging self-care by patients were widely recognised in terms of their impact on patients, health professionals and wider society. Although some challenges of introducing a new service were identified, these did not appear to be insurmountable. CONCLUSIONS: CAS was welcomed by stakeholders in terms of its potential benefits. Results are therefore encouraging for policy makers involved in the implementation of other new roles within community pharmacy in the UK and beyond. PMID- 26670862 TI - A coil system for real-time magnetic fluid hyperthermia microscopy studies. AB - PURPOSE: We describe the design and application of a new apparatus for applying Radiofrequency (RF) electromagnetic fields to cells in culture on a microscope stage. This new design enables real-time studies of the actuation of magnetic nanoparticles bound to membrane receptors or internalised within cells together with the study of magnetic fluid hyperthermia (MFH)-associated effects. MATERIALS AND METHODS: RF coils were fabricated and electromagnetic simulations were performed along with compatibility evaluations and calorimetric experiments using this apparatus at discreet frequencies between 100 kHz and 1 MHz. Cell killing via MFH was investigated in a neuroblastoma tumour cell line. RESULTS: Simulations and evaluations showed that the field intensity and homogeneity experienced by the cells within the chamber is best with a planar coil configuration. The incubation chamber was suitable for cell culture and the design was compatible with mountings on different makes of microscopes as it mimics a standard 96/24/6 tissue-culture well plate. Successful calorimetric and MFH cytotoxicity proof-of-principle experiments were performed and are presented. CONCLUSIONS: We conclude from these experiments that alternating magnetic field (AMF)-mediated activation and magnetic fluid hyperthermia (MFH) research will benefit from this RF coil that fits inside an incubation chamber, mounted onto a microscope. This new design could be used to assist real-time MFH studies in vitro. PMID- 26670863 TI - Bone mineral density in MPS IV A (Morquio syndrome type A). AB - Mucopolysaccharidosis IV A (MPS IV A), Morquio A, is caused by deficiency in lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which is responsible for the catabolism of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S). Accumulation of GAGs results in disrupted cartilage formation and skeletal dysplasia. In this prospective cross-sectional study, bone mineral density (BMD) of the whole body (WB), lumbar spine (LS), and lateral distal femur (LDF) was acquired by dual-energy X-ray absorptiometry (DXA) on patients with MPS IV A. Functional abilities, medical history, Tanner score, and laboratory results were reviewed. Age and sex-matched norms were used to calculate Z-scores. Participants included 18 patients (13 females; 16 were unrelated) with a mean age of 21.4years (3.3 to 40.8years). While every patient was able to bear weight, 9 were full-time ambulators. Whole-body DXA could be obtained on only 6 patients (5 full-time ambulators) because of respiratory compromise caused by the position, presence of hardware, or positioning difficulties. Mean WB Z-score was -2.0 (range-0.3 to -4.1). Technical issues invalidating LS DXA in 8 patients included kyphosis at the thoracolumbar junction resulting in overlap of vertebrae in the posterior-anterior view. Mean LS BMD Z score in full-time ambulators was -3.4 (range-1.6 to -5.0) and in the non /partial ambulator was -4.0 (-3.7 to -4.2). Lateral distal femur BMD was acquired on every patient, and average Z-scores were -2 or less at all sites; full-time ambulators exhibited higher BMD. In conclusion, the LDF proved to be the most feasible site to measure in patients with MPS IV A. The higher LDF values in ambulators suggest this should be a consideration in promoting bone health for this group. PMID- 26670865 TI - Clinical characteristics associated with esophageal motility function. AB - BACKGROUND AND AIM: Esophageal motility disorders (EMDs) affect coordinated esophageal contractility. Recent developments in high-resolution manometry have improved diagnosis of EMDs; however, the etiology of EMDs remains to be determined. This study aimed to determine which clinical characteristics are associated with esophageal motility. METHODS: From May 2013 to July 2014, 97 patients (54 women, 43 men; age, 16-89 years) with suspected EMDs were assessed by high-resolution manometry in Kyushu University Hospital. Esophageal motility was evaluated by measuring the distal contractile integral (DCI), basal lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). Data on age, gender, body mass index (BMI), Brinkman Index, and blood tests were retrospectively collected and analyzed. RESULTS: Fifty patients were diagnosed as normal, nine with achalasia, twelve with esophagogastric junction outflow obstruction, four with distal esophageal spasm, one with jackhammer esophagus, six with absent peristalsis, ten with frequent failed peristalsis, and five with weak peristalsis. The median DCI was 1229.0 mmHg-s-cm, the median basal lower esophageal sphincter pressure was 25.3 mmHg, and the median IRP was 9.6 mmHg. Patients with major motility disorders were excluded from analysis. By multivariate regression analysis, BMI (P = 0.029) and total cholesterol (P = 0.023) were negatively associated with DCI, while BMI (P = 0.007) was negatively associated with IRP and glucose (P = 0.044) was positively associated with IRP. CONCLUSIONS: Both BMI and total cholesterol could be highly predictive factors for esophageal body contractility, while BMI and glucose could be predictive factors for lower esophageal sphincter contractile function. PMID- 26670866 TI - Young Australian women explain their contraceptive choices. AB - New developments in female contraceptives allow women increased options for preventing pregnancy, while men's options for reversible contraception have not advanced beyond the condom. There has been little discursive exploration of how neoliberal and postfeminist discourses shape women's accounts of choosing whether or not to use contraception. Our thematic discourse analysis of 760 free-text responses to a question about contraceptive choice considers the social and political climate that promotes the self-governed woman who freely chooses contraception. We examine the ways in which women formulated and defended their accounts of choice, focusing on the theme of free contraceptive choice that constructed women's choices as unconstrained by material, social and political forces. We identify two discursive strategies that underpinned this theme: a woman's body, a woman's choice and planning parenthood, and explore the ways in which choice was understood as a gendered entitlement and how contraceptive choices were shaped (and constrained) by women's plans for parenthood. We discuss the implications of these discursive strategies, and neoliberal and postfeminist discourses, in terms of the disallowance of any contextual, social and structural factors, including the absence of men in the 'contraceptive economy'. PMID- 26670864 TI - Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity. AB - Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2) and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons. PMID- 26670867 TI - Can circulating miRNAs live up to the promise of being minimal invasive biomarkers in clinical settings? AB - MicroRNAs have been discussed as non- or minimal invasive biomarkers with a remarkable extracellular stability. Despite a multitude of studies in basic research, there are only few independent validation studies on blood-born miRNAs as disease markers. Toward clinical applications numerous obstacles still need to be overcome. They are of technical origin but also fundamentally associated with the source and the nature of miRNAs. Here, we emphasize on potential confounding factors, the nature and the source of miRNAs. We recently showed that age and gender could influence the pattern of circulating miRNAs. On the cellular level, the miRNA pattern differs between plasma and serum preparations. On the molecular level, one has to differentiate between extracellular miRNAs that are encapsulated in microvesicles or bound to proteins or high-density lipoproteins. Using whole blood as source for miRNAs helps to minimize miRNA expression changes due to environmental influences and allows attributing miRNA changes to their cells of origin like B-cells and T-cells. Moreover, unambiguous annotation and differentiation from other noncoding RNAs can be challenging. Even not all miRNAs deposited in miRBase do necessarily represent true miRNAs, just a fraction of miRNAs in the reference database have been experimentally validated by Northern blotting. Functional evidence for a true miRNA should be obtained by cloning the precursor miRNA and by subsequent detection of the processed mature form in host cells. Surprisingly, attempts to finally confirm a true miRNA are frequently postponed until evidence has been established for a likely value as biomarker. PMID- 26670868 TI - Text message content preferences to improve buprenorphine maintenance treatment in primary care. AB - Few studies have evaluated text message content preferences to support evidence based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a "few months" into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed. PMID- 26670869 TI - Facile method for preparing superoleophobic surfaces with hierarchical microcubic/nanowire structures. AB - To facilitate the fabrication of superoleophobic surfaces having hierarchical microcubic/nanowire structures (HMNS), even for low surface tension liquids including octane (surface tension = 21.1 mN m(-1)), and to understand the influences of surface structures on the oleophobicity, we developed a convenient method to achieve superoleophobic surfaces on aluminum substrates using chemical acid etching, anodization and fluorination treatment. The liquid repellency of the structured surface was validated through observable experimental results; the contact and sliding angle measurements. The etching condition required to ensure high surface roughness was established, and an optimal anodizing condition was determined, as a critical parameter in building the superoleophobicity. The microcubic structures formed by acid etching are essential for achieving the formation of the hierarchical structure, and therefore, the nanowire structures formed by anodization lead to an enhancement of the superoleophobicity for low surface tension liquids. Under optimized morphology by microcubic/nanowire structures with fluorination treatment, the contact angle over 150 degrees and the sliding angle less than 10 degrees are achieved even for octane. PMID- 26670870 TI - Perceived barriers to medication adherence in pediatric and adolescent solid organ transplantation. AB - Comparisons of perceived barriers to adherence in pediatric and adolescent SOT have not been systematically conducted despite association between medication non adherence and poor outcome. Fifteen centers in CTOT-C enrolled patients in a cross-sectional study. Subjects' guardians completed the PMBS and subjects over eight completed the Adolescent Scale (AMBS). Association of three identified PMBS factors and subject age was assessed. Secondary analyses assessed associations between PMBS, AMBS, and patient demographics. Three hundred sixty-eight subjects or their guardians completed PMBS or AMBS. A total of 107 subjects were 6-11 yr; 261 were >=12. Unadjusted and propensity-adjusted analyses indicated higher perceived barriers in guardians of adolescents as compared to guardians of pre adolescents medication scheduling and frustration domains regardless of organ (p < 0.05). PMBS and AMBS comparisons revealed that guardians reported fewer ingestion issues than patients (p = 0.018), and differences appeared more pronounced within younger responders for scheduling (p = 0.025) and frustration (p = 0.019). Screening revealed guardians of older patients report increased perceived barriers to adherence independent of socioeconomic status. Guardians of adolescents reported fewer perceived barriers to ingestion/side effects than patients themselves, particularly in pre-adolescents (8-11 yr). Brief screening measures to assess perceived barriers should be further studied in adherence improvement programs. PMID- 26670880 TI - Some like it hot, but not too hot. AB - A temperature-sensitive receptor prevents mosquitoes from being attracted to targets that are hotter than a potential host. PMID- 26670882 TI - Survival rates after bowel cancer surgery rise in England and Wales. PMID- 26670881 TI - Development and evaluation of mosquito-electrocuting traps as alternatives to the human landing catch technique for sampling host-seeking malaria vectors. AB - BACKGROUND: The human landing catch (HLC) is the gold standard method for sampling host-seeking malaria vectors. However, the HLC is ethically questionable because it requires exposure of humans to potentially infectious mosquito bites. METHODS: Two exposure-free methods for sampling host-seeking mosquitoes were evaluated using electrocuting surfaces as potential replacements for HLC: (1) a previously evaluated, commercially available electrocuting grid (CA-EG) designed for killing flies, and (2) a custom-made mosquito electrocuting trap (MET) designed to kill African malaria vectors. The MET and the CA-EG were evaluated relative to the HLC in a Latin Square experiment conducted in the Kilombero Valley, Tanzania. The sampling consistency of the traps across the night and at varying mosquito densities was investigated. Estimates of the proportion of mosquitoes caught indoors (P(i)), proportion of human exposure occurring indoors (pi(i)), and proportion of mosquitoes caught when most people are likely to be indoors (P(fl)) were compared for all traps. RESULTS: Whereas the CA-EG performed poorly (<10% of catch of HLC), sampling efficiency of the MET for sampling Anopheles funestus s.l. was indistinguishable from HLC indoors and outdoors. For Anopheles gambiae s.l., sampling sensitivity of MET was 20.9% (95% CI 10.3-42.2) indoors and 58.5% (95% CI 32.2-106.2) outdoors relative to HLC. There was no evidence of density-dependent sampling by the MET or CA-EG. Similar estimates of P(i) were obtained for An. gambiae s.l. and An. funestus s.l. from all trapping methods. The proportion of mosquitoes caught when people are usually indoors (P(fl)) was underestimated by the CA-EG and MET for An. gambiae s.l., but similar to the HLC for An. funestus. Estimates of the proportion of human exposure occurring indoors (pi(i)) obtained from the CA-EG and MET were similar to the HLC for An. gambiae s.l., but overestimated for An. funestus. CONCLUSIONS: The MET showed promise as an outdoor sampling tool for malaria vectors where it achieved >50% sampling sensitivity relative to the HLC. The CA-EG had poor sampling sensitivity outdoors and inside. With further modification, the MET could provide an efficient and safer alternative to the HLC for the surveillance of mosquito vectors outdoors. PMID- 26670884 TI - Thermodynamic Control of Isomerizations of Bicyclic Radicals: Interplay of Ring Strain and Radical Stabilization. AB - The rearrangements of 4-substituted bicyclo[2.2.2]oct-5-en-2-yl radicals, generated from the corresponding Diels-Alder adducts with phenylseleno acrylates by radical-induced reductive deselenocarbonylations, give the 2-substituted bicyclo[3.2.1]oct-6-en-2-yl radicals with some substituents, e.g., alkoxy and phenyl, but not for silyloxymethyl or benzyl substituents. Theoretical calculations with DFT give the thermodynamics of these reactions and the origins of these processes. PMID- 26670883 TI - Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon Biased Translation. AB - Post-transcriptional modifications of transfer RNAs (tRNAs) have long been recognized to play crucial roles in regulating the rate and fidelity of translation. However, the extent to which they determine global protein production remains poorly understood. Here we use quantitative proteomics to show a direct link between wobble uridine 5-methoxycarbonylmethyl (mcm5) and 5-methoxy carbonyl-methyl-2-thio (mcm5s2) modifications catalyzed by tRNA methyltransferase 9 (Trm9) in tRNAArg(UCU) and tRNAGlu(UUC) and selective translation of proteins from genes enriched with their cognate codons. Controlling for bias in protein expression and alternations in mRNA expression, we find that loss of Trm9 selectively impairs expression of proteins from genes enriched with AGA and GAA codons under both normal and stress conditions. Moreover, we show that AGA and GAA codons occur with high frequency in clusters along the transcripts, which may play a role in modulating translation. Consistent with these results, proteins subject to enhanced ribosome pausing in yeast lacking mcm5U and mcm5s2U are more likely to be down-regulated and contain a larger number of AGA/GAA clusters. Together, these results suggest that Trm9-catalyzed tRNA modifications play a significant role in regulating protein expression within the cell. PMID- 26670885 TI - Retinal Phenotype following Combined Deletion of the Chemokine Receptor CCR2 and the Chemokine CX3CL1 in Mice. AB - PURPOSE: Conflicting data were reported with respect to the retinal phenotype of mice with dual perturbation of the CCL2 and CX3CR1 genes. We report the generation and retinal phenotype of mice with a reverse CCR2/CX3CL1 gene deficiency as a suggested model for age-related macular degeneration (AMD). METHODS: Crossing of single-deficient mice generated CCR2/CX3CL1 DKO mice. DKO mice were compared with age-matched C57BL6J mice. Evaluation included color fundus photographs, electroretinography (ERG), histology and morphometric analysis. Immunohistochemistry for CD11b in retinal cross-sections and retinal pigment epithelium (RPE)-choroid flat mounts was performed to assess microglia and macrophage recruitment. RESULTS: A minority of DKO mice showed yellowish subretinal deposits at 10 months. ERG recordings showed reduced cone sensitivity in young, but not older DKO mice. Compared to wild-type mice, DKO mice exhibited 11% reduction in the number of outer nuclear layer nuclei. Old DKO mice had an increased number of CD11b-positive cells across the retina, and on RPE-choroid flat mounts. CONCLUSIONS: In the absence of the rd8 allele, deficiency of CCR2 and CX3CL1 in mice leads to a mild form of retinal degeneration which is associated with the recruitment of macrophages, particularly to the subretinal space. This model enables to assess consequences of perturbed chemokine signaling, but it does not recapitulate cardinal AMD features. PMID- 26670886 TI - Prevalence of abnormal birth weight and related factors in Northern region, Ghana. AB - BACKGROUND: Birth weight is a crucial determinant of the development potential of the newborn. Abnormal newborn weights are associated with negative effects on the health and survival of the baby and the mother. Therefore, this study was designed to determine the prevalence of abnormal birth weight and related factors in Northern region, Ghana. METHODS: The study was a facility-based cross sectional survey in five hospitals in Northern region, Ghana. These hospitals were selected based on the different socio-economic backgrounds of their clients. The data on birth weight and other factors were derived from hospital records. RESULTS: It was observed that low birth weight is still highly prevalent (29.6%), while macrosomia (10.5%) is also increasingly becoming important. There were marginal differences in low birth weight observed across public hospitals but marked difference in low birth weight was observed in Cienfuegos Suglo Specialist Hospital (Private hospital) as compared to the public hospitals. The private hospital also had the highest prevalence of macrosomia (20.1%). Parity (0-1) (p < 0.001), female gender (p < 0.001) and location (rural) (p < 0.001) were significantly associated with decreased risk of macrosomic births. On the other hand, female infant sex (p < 0.001), residential status (rural) (p < 0.001) and parity (0-1) (p < 0.001) were significantly associated with increased risk of low birth weigh. CONCLUSIONS: Our findings show that under nutrition (low birth weight) and over nutrition (macrosomia) coexist among infants at birth in Northern region reflecting the double burden of malnutrition phenomenon, which is currently being experienced by developing and transition counties. Both low birth weight and macrosomia are risk factors, which could contribute considerably to the current and future burden of diseases. This may overstretch the already fragile health system in Ghana. Therefore, it is prudent to recommend that policies aiming at reducing diet related diseases should focus on addressing malnutrition during pregnancy and early life. PMID- 26670887 TI - Ganciclovir concentrations in the cerebral extracellular space after valganciclovir treatment; a case study. AB - Nearly all glioblastomas (GBMs), brain tumours with very poor prognosis, are infected with human cytomegalovirus (CMV). The anti-CMV drug valganciclovir (VGCV) has shown promise as a treatment option for patients with GBM, but its penetration into the central nervous system (CNS) is unknown. Here we describe a patient with GMB receiving VGCV in whom an intracerebral microdialysis catheter was implanted and ganciclovir (GCV) concentrations in brain extracellular fluid (BECF) and serum were monitored. GCV was rapidly absorbed. Cmax values (at 3 h) in serum and BECF were 19.6 and 10.2 umol/L, T1/2 values were 3.2 and 4.5 h, and plasma and BECF AUC0-infinity values were 90.7 and 75.9 umol h/L, respectively. Thus, VGCV treatment results in significant intracerebral levels of GCV that may be sufficient for therapeutic effects. Further studies of this drug in patients with GBM are warranted. PMID- 26670888 TI - The woman with unexplained anaemia. AB - A 77-year-old woman was admitted to hospital for 3 weeks to treat cellulitis and investigate unexplained anaemia. Earlier, when her neck had been examined on outpatient review of her lymphoedema, a large fungating tumour had been noted. This was biopsied and found to be a mixed basaloid adenocarcinoma. She was subsequently admitted under the plastic surgeons and treated with wide local excision on postero-lateral neck dissection. The defect was reconstructed with a deltopectoral flap. PMID- 26670889 TI - Glass fragment embedded in the cheek: a missed radiographic finding. PMID- 26670890 TI - Leukemoid reaction as a paraneoplastic syndrome in hypopharyngeal squamous cell carcinoma with cutaneous metastasis: an exceedingly rare occurrence. AB - Head and neck squamous cell carcinoma is considered a locoregional disease, with a distinct chance of metastasis, however, skin is an unusual site. Haematological paraneoplastic syndromes are even rarer, and may be the only presenting feature in these malignancies, producing diagnostic confusion. Cutaneous metastasis, in addition to signifying poor response to treatment and prognosis, can cause diagnostic difficulty if the metastasis is located with an occult primary, and is associated with a higher incidence of multiple synchronous primaries. This article describes a 52-year-old patient with multiple swellings on the left side of the neck and hoarseness of voice. On evaluation, the multiple swellings were found to be cutaneous metastasis from a hypopharyngeal squamous cell carcinoma, with a leukemoid reaction. He opted for palliative radiotherapy and succumbed to his illness within 3 months of presentation. This article discusses the importance of this unusual presentation and diagnostic difficulties associated with it. PMID- 26670891 TI - Early bilateral nephrectomy in infantile autosomal recessive polycystic kidney disease. AB - The management of neonatal autosomal recessive polycystic kidney disease (ARPKD) complicated by severe pulmonary insufficiency presents complex clinical challenges. Where massive nephromegaly exists, early bilateral nephrectomy, supportive peritoneal dialysis and early aggressive nutrition can minimise infant mortality. Consensus, however, is lacking on the role and optimal timing of nephrectomy, with decision-making driven by the patient's clinical condition and the expertise of the centre. We report on our experience of an infant with ARPKD requiring neonatal renal replacement therapy and survival at 14 months following early bilateral nephrectomy. PMID- 26670892 TI - Sudden onset unilateral sensorineural hearing loss after rabies vaccination. AB - A 33-year-old man developed profound sudden onset right-sided hearing loss with tinnitus and vertigo, within 24 h of pretravel rabies vaccination. There was no history of upper respiratory tract infection, systemic illness, ototoxic medication or trauma, and normal otoscopic examination. Pure tone audiograms (PTA) demonstrated right-sided sensorineural hearing loss (thresholds 90-100 dB) and normal left-sided hearing. MRI internal acoustic meatus, viral serology (hepatitis B, C, HIV and cytomegalovirus) and syphilis screen were normal. Positive Epstein-Barr virus IgG, viral capsid IgG and anticochlear antibodies (anti-HSP-70) were noted. Initial treatment involved a course of high-dose oral prednisolone and acyclovir. Repeat PTAs after 12 days of treatment showed a small improvement in hearing thresholds. Salvage intratympanic steroid injections were attempted but failed to improve hearing further. Sudden onset sensorineural hearing loss (SSNHL) is an uncommon but frightening experience for patients. This is the first report of SSNHL following rabies immunisation in an adult. PMID- 26670893 TI - Postpartum acute abdomen and its diagnostic challenges. AB - This is the case of a 25-year-old primigravida with gradual onset abdominal pain and vomiting, 1 day postvaginal delivery. After three hospital admissions over the following 3 weeks, a diagnosis of small bowel obstruction secondary to adhesions was made; the patient had undergone a previous appendicectomy. The patient was taken to theatre for laparotomy and adhesiolysis, where the bowel was found to be viable but with two small serosal tears. Postoperative recovery was uncomplicated. This case highlights the importance of assessing abdominal pain in the puerperium in a similar manner to that done in a non-pregnant state, to avoid delay in diagnosis. PMID- 26670894 TI - Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient. AB - Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. PMID- 26670896 TI - Insulinoma with focal hepatic lesions: malignant insulinoma? AB - Insulinoma is a rare tumour that is malignant in only 10% of cases. We report a case of insulinoma in a 59-year-old woman, associated with focal liver lesions, which raised the suspicion of malignancy of a pancreatic tumour. Enucleation of the insulinoma was performed with wedge resection of one hepatic nodule. Pathological examination indicated that the pancreatic tumour was compatible with insulinoma whereas the hepatic lesion was related to focal nodular hyperplasia. This clinical case highlights the need for histopathological proof of malignancy before selecting therapeutic strategies for insulinomas. PMID- 26670895 TI - Thyroid storm in a patient with Wolff-Parkinson-White syndrome. AB - A 44-year-old woman with no medical history presented to the emergency department with a 2 h history of sudden onset chest pressure, palpitations, diaphoresis and shortness of breath. She reported a 90-pound unintentional weight loss, increased appetite, irritability, night sweats and palpitations for 2 months. Physical examination revealed a heart rate (HR) of 269 bpm and a blood pressure of 116/94 mm Hg. Her ECG revealed a wide-complex tachycardia with right bundle branch morphology and an HR of 265 bpm. Intravenous adenosine was administered with resolution of the arrhythmia and symptoms. Her subsequent ECG revealed sinus tachycardia with delta waves, which was consistent with Wolff-Parkinson-White (WPW) syndrome. Laboratory findings confirmed thyroid storm and treatment began with intravenous hydrocortisone, methimazole, metoprolol, amiodarone and iodine drops. Graves' disease was confirmed based on the presence of serum thyroid stimulating hormone receptor antibody. The patient underwent successful WPW accessory tract ablation 6 weeks after initial presentation. PMID- 26670897 TI - Congenital pseudoarthrosis in a child with neurofibromatosis. PMID- 26670898 TI - Splenic abscess due to Salmonella schwarzengrund in a previously healthy individual returning from Bali. AB - After an episode of diarrhoea, a previously healthy young man developed a splenic abscess due to invasive non-typhoidal Salmonella. The patient was presented with >1 month of fever, diffuse abdominal pain, raised C reactive protein and increased white cell count. Ultrasonography revealed a 5 * 5 cm abscess in the spleen. After an unsuccessful treatment attempt with percutaneous drainage and antibiotics, the patient was successfully treated with splenectomy and antibiotics. This case highlights the difficulties inherent in making a correct diagnosis of splenic abscess in patients without risk factors. Splenic abscess is rare in previously healthy individuals. Antibiotics are inadequate as a sole treatment, and percutaneous drainage is usually only a temporary solution. Splenectomy is still the standard treatment in most cases. PMID- 26670899 TI - Feeling blue, going green and finding other attractive alternatives: a case of biphasic anaphylaxis to patent blue and a literature review of alternative sentinel node localisation methods. AB - Patent blue dye is used for sentinel lymph node localisation in order to stage the axilla in patients with breast cancer. Patent blue is one of the most common dyes used across the UK, however, the incidence of adverse effects seems to be increasing. This case highlights our experience of a biphasic anaphylactic reaction to patent blue dye, and we conduct a brief literature review of alternative and more novel methods to adequately visualise the lymphatics for sentinel lymph node biopsy. PMID- 26670900 TI - PET artefact masquerading as a PET positive lung mass. PMID- 26670901 TI - Airway management of a life-threatening post-thyroidectomy haematoma. AB - Neck haematomas are rare but potentially life-threatening complications of thyroid surgery. Postoperative monitoring, early diagnosis and immediate management are critical, as this condition can rapidly lead to compression and obstruction of the upper airway. We present a case of a 69-year-old woman who suffered respiratory failure resulting from a post-thyroidectomy haematoma with airway obstruction and severe haemodynamic compromise, presenting a difficult anaesthetic challenge. Following development of a likely 'cannot intubate, cannot ventilate' situation despite haematoma evacuation, the patient underwent emergency cricothyroidotomy, before rapid sequence intubation and subsequent surgical haemostasis. PMID- 26670902 TI - Ultra-wide field imaging in peripheral exudative haemorrhagic chorioretinopathy (PEHCR). PMID- 26670904 TI - Eyeglasses elicit effects similar to face-like perceptual expertise: evidence from the N170 response. AB - Studies of event-related potentials show that the specific N170 response has become a stable electrophysiological hallmark of objects related to expertise in early perceptual processing. In the present study, we investigated whether eyeglasses can elicit N170 effects similar to those elicited by objects of expertise. Our results showed that the N170 response elicited by eyeglasses was larger than the response elicited by objects that do not generate perceptual expertise (e.g., houses). Importantly, we found that eyeglasses could produce a within-category N170 adaptation effect, similar to that produced in response to objects of expertise (e.g., faces). Our results have revealed for the first time that with a large amount of experience, eyeglasses could evoke the face-like N170 response, which suggested that eyeglasses may become an object of perceptual expertise to some human observers. PMID- 26670903 TI - Heme oxygenase-1 attenuates cadmium-induced mitochondrial-caspase 3- dependent apoptosis in human hepatoma cell line. AB - BACKGROUND: Cadmium (Cd) is a well known environmental and industrial toxicant causing damaging effects in numerous organs. In this study, we examined the role of heme oxygenase-1 (HO-1) in modulating the Cd-induced apoptosis in human hepatoma (HepG2) cells after 24 h exposure. METHODS: HepG2 cells were exposed to 5 and 10 MUM Cd as CdCl2 for 24 h while other sets of cells were pre-treated with either 10 MUM Cobalt protoporphyrin (CoPPIX) or 10 MUM Tin protoporphyrin (SnPPIX) for 24 h, or 50 MUM Z-DEVD-FMK for 1 h before exposure to 5 and 10 MUM CdCl2 for 24 h. Expressions of caspase 3, cytosolic cytochrome c, mitochondrial Bax and anti-apoptotic BCL-xl proteins were assessed by western blot. Intracellular reactive oxygen species (ROS) production was determined using the dihydrofluorescein diacetate (H2DFA) method. Cell viability was assessed by MTT assay, while a flow cytometry method was used to assess the level of apoptosis in the cell populations. RESULTS: Our results show that there were a significant increase in the expression of cytosolic cytochrome c, mitochondrial Bax protein, and caspase 3 at 5 and 10 MUM compared to the control, but these increases were attenuated by the presence of CoPPIX. The presence of SnPPIX significantly enhanced Cd-induced caspase 3 activities. CoPPIX significantly decreased the level of ROS production by 24.6 and 22.2 % in 5 and 10 MUM CdCl2, respectively, but SnPPIX caused a significant increase in ROS production in the presence of CdCl2. HepG2 cell viability was also significantly impaired by 13.89 and 32.53 % in the presence of 5 and 10 MUM CdCl2, respectively, but the presence of CoPPIX and Z-DEVD-FMK significantly enhanced cell survival, while SnPPIX enhanced Cd impaired cell viability. The presence of CoPPIX and Z-DEVD-FMK also significantly decreased the population of apoptotic and necrotic cells compared with Cd. CONCLUSION: In summary, the present study showed that HO-1 attenuates the Cd induced caspase 3 dependent pathway of apoptosis in HepG2 cells, probably by modulating Cd-induced oxidative stress. PMID- 26670905 TI - Cross-modal perceptual load: the impact of modality and individual differences. AB - Visual distractor processing tends to be more pronounced when the perceptual load (PL) of a task is low compared to when it is high [perpetual load theory (PLT); Lavie in J Exp Psychol Hum Percept Perform 21(3):451-468, 1995]. While PLT is well established in the visual domain, application to cross-modal processing has produced mixed results, and the current study was designed in an attempt to improve previous methodologies. First, we assessed PLT using response competition, a typical metric from the uni-modal domain. Second, we looked at the impact of auditory load on visual distractors, and of visual load on auditory distractors, within the same individual. Third, we compared individual uni- and cross-modal selective attention abilities, by correlating performance with the visual Attentional Network Test (ANT). Fourth, we obtained a measure of the relative processing efficiency between vision and audition, to investigate whether processing ease influences the extent of distractor processing. Although distractor processing was evident during both attend auditory and attend visual conditions, we found that PL did not modulate processing of either visual or auditory distractors. We also found support for a correlation between the uni modal (visual) ANT and our cross-modal task but only when the distractors were visual. Finally, although auditory processing was more impacted by visual distractors, our measure of processing efficiency only accounted for this asymmetry in the auditory high-load condition. The results are discussed with respect to the continued debate regarding the shared or separate nature of processing resources across modalities. PMID- 26670906 TI - Sensorimotor integration is enhanced in dancers and musicians. AB - Studying individuals with specialized training, such as dancers and musicians, provides an opportunity to investigate how intensive practice of sensorimotor skills affects behavioural performance across various domains. While several studies have found that musicians have improved motor, perceptual and sensorimotor integration skills compared to untrained controls, fewer studies have examined the effect of dance training on such skills. Moreover, no study has specifically compared the effects of dance versus music training on perceptual or sensorimotor performance. To this aim, in the present study, expert dancers, expert musicians and untrained controls were tested on a range of perceptual and sensorimotor tasks designed to discriminate performance profiles across groups. Dancers performed better than musicians and controls on a dance imitation task (involving whole-body movement), but musicians performed better than dancers and controls on a musical melody discrimination task as well as on a rhythm synchronization task (involving finger tapping). These results indicate that long term intensive dance and music training are associated with distinct enhancements in sensorimotor skills. This novel work advances knowledge of the effects of long term dance versus music training and has potential applications in therapies for motor disorders. PMID- 26670907 TI - Subliminal trauma reminders impact neural processing of cognitive control in adults with developmental earthquake trauma: a preliminary report. AB - Little is known about the effects of developmental trauma on the neural basis of cognitive control among adults who do not have posttraumatic stress disorder. To examine this question, we used functional magnetic resonance imaging to compare the effect of subliminal priming with earthquake-related images on attentional control during a Stroop task in survivors of the 2008 Wenchuan earthquake in China (survivor group, survivors were adolescents at the time of the earthquake) and in matched controls (control group). We found that the survivor group showed greater activation in the left ventral anterior cingulate cortex (vACC) and the bilateral parahippocampal gyrus during the congruent versus incongruent condition, as compared to the control group. Depressive symptoms were positively correlated with left vACC activation during the congruent condition. Moreover, psychophysiological interaction results showed that the survivor group had stronger functional connectivity between the left parahippocampal gyrus and the left vACC than the control group under the congruent-incongruent condition. These results suggested that trauma-related information was linked to abnormal activity in brain networks associated with cognitive control (e.g., vACC-parahippocampal gyrus). This may be a potential biomarker for depression following developmental trauma, and it may also provide a mechanism linking trauma reminders with depression. PMID- 26670910 TI - Do Early Seizures Indicate Survival of Patients with Nontraumatic Intracerebral Hemorrhage? AB - BACKGROUND AND PURPOSE: Early seizures (ESs) in patients with nontraumatic spontaneous intracerebral hemorrhage (sICH) are a frequent complication. The aims of this study were to determine the frequency of ESs in patients with sICH and to investigate the association of ESs with outcomes in a monocenter study. METHODS: During a 5-year period (2009-2013), 484 consecutive patients (mean age 72.3 +/- 12.6; female sex 51%) with sICH who were admitted to the Department of Neurology at the University of Lubeck, Germany were enrolled and prospectively evaluated. RESULTS: A total of 52 patients (10.7%; 95% CI 8-14) experienced ESs during a mean hospitalization of 12 days. Patients with ESs were less affected on the National Institutes of Health Stroke Scale at admission than those without ESs (7 vs. 10; p = 0.02). With the exception of the localization of hemorrhage (p = 0.008), differences in the baseline characteristics between patients with ESs and those without ESs were not found. The logistic regression analysis revealed an increased ES rate in patients with cortical hemispheric sICH (OR 3.5; 95% CI 1.8 6.7; p < 0.001). During hospitalization, 109 patients (23%) died and the in hospital mortality was lower in patients with ESs than those without (9.6 vs. 24.0%, respectively; p = 0.02). An association between ESs and good functional outcome on the modified Rankin Scale <= 2 was not found (p = 0.3). CONCLUSION: ESs appear to be correlated with hemorrhage localization and associated with survival of the sICH. PMID- 26670908 TI - Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus (RSV). AB - Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection. PMID- 26670909 TI - Myocardial injury associated with transcatheter aortic valve implantation (TAVI). AB - Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment option for elderly patients with symptomatic aortic stenosis whose risk is too high or prohibitive for conventional surgery. Despite notable progress during the past decade, continuous efforts directed at further improvement of procedural safety and performance are required, especially considering expanding indications for interventional treatment options among lower-risk populations. One issue that needs to be addressed is myocardial damage, which can frequently be observed after TAVI and has been linked to worse prognosis. Yet, knowledge concerning the underlying mechanisms and clinical impact remains scarce, and further investigation in this field is warranted. In this review, we provide a contemporary summary of the types of myocardial injury associated with TAVI, including access-related injury, mechanical trauma and ischemia, the role of myocardial biomarkers, and the impact on left ventricular function, with emphasis on potential mechanisms and clinical implications. PMID- 26670911 TI - Secondary syphilis presenting with aortitis and coronary ostial occlusion. AB - Aortitis is an established manifestation of tertiary syphilis. We report a rare case of aortitis with ostial occlusion and left ventricular failure in secondary syphilis. Her management required a true multidisciplinary approach from multiple specialities due to complications of concomitant psychosis and a history of anaphylaxis to penicillin. This case illustrates the complexities of diagnosing and managing a rare presentation of this increasingly prevalent infection. PMID- 26670912 TI - 'It's all in the message': the utility of personalised short message service (SMS) texts to remind patients at higher risk of STIs and HIV to reattend for testing-a repeat before and after study. AB - BACKGROUND: Patients at increased risk of sexually transmitted infections (STIs)/HIV acquisition are advised to reattend for retesting. A previous study showed that 'generic' text reminders did not improve reattendance. AIM: To assess if a personalised text message with increased contact information would increase reattendance rates of at-risk patients. METHODS: Patients who are at risk of future STIs, defined by having a current acute STI, attending for emergency contraception, commercial sex workers (CSWs) or men who have sex with men (MSM), were sent a text reminder to reattend for retesting 6 weeks after initial visit. Reattendance rates were measured for September to December 2012 (control group who received a generic text message) and February to May 2014 (intervention 'personalised message' group who received a text message containing their first name and ways to contact the clinic). Reattendance was counted within 4 months of the end of the initial episode of care. RESULTS: The reattendance rate was significantly higher for the intervention group: 149/266 (56%) than the control group: 90/273 (33%) (p=0.0001) and was also significantly higher in the intervention group than the control group in patients with the following risks: recent chlamydia (64/123 (52%) vs 43/121 (36%)) (p=0.03), recent gonorrhoea (41/64 (64%) vs 4/21 (19%)) (p=0.0003) and MSM (26/45 (58%) vs 3/18 (16%)) (p=0.006). New STI rates in the reattending intervention group and controls were 26/ 149 (17%) and 13/90 (14%) (n.s), respectively. CONCLUSIONS: Sending a personalised text message with increased contact information as a reminder for retesting increased reattendance rates by 23% in patients who are at higher risk of STIs. PMID- 26670913 TI - Sexual abstinence and other behaviours immediately following a new STI diagnosis among STI clinic patients: Findings from the Safe in the City trial. AB - BACKGROUND: Few studies have assessed patients' sexual behaviours during the period immediately following a new diagnosis of a curable sexually transmitted infection (STI). METHODS: Data were analysed from a behavioural study nested within the Safe in the City trial, which evaluated a video-based STI/HIV prevention intervention in three urban STI clinics. We studied 450 patients who reported having received a new STI diagnosis, or STI treatment, 3 months earlier. Participants reported on whether they seriously considered, attempted and succeeded in adopting seven sex-related behaviours in the interval following the diagnostic visit. We used multivariable logistic regression to identify, among men, correlates of two behaviours related to immediately reducing reinfection risk and preventing further STI transmission: sexual abstinence until participants were adequately treated and abstinence until their partners were tested for STIs. RESULTS: Most participants reported successfully abstaining from sex until they were adequately treated for their baseline infection (89%-90%) and from sex with potentially exposed partners until their partners were tested for HIV and other STIs (66%-70%). Among men who intended to be abstinent until they were adequately treated, those who did not discuss the risks with a partner who was possibly exposed were more likely not to be abstinent (OR, 3.7; 95% CI 1.5 to 9.0) than those who had this discussion. Similarly, among men who intended to abstain from sex with any potentially exposed partner until the partner was tested for HIV and other STIs, those who reported not discussing the risks of infecting each other with HIV/STIs were more likely to be sexually active during this period (OR, 3.5; 95% CI 1.6 to 8.1) than were those who reported this communication. CONCLUSIONS: Improved partner communication could facilitate an important role in the adoption of protective behaviours in the interval immediately after receiving a new STI diagnosis. TRIAL REGISTRATION NUMBER: NCT00137670. PMID- 26670914 TI - Field evaluation of a dual rapid diagnostic test for HIV infection and syphilis in Lima, Peru. AB - OBJECTIVES: Screening for HIV and syphilis in key populations is recommended by the WHO to reduce the morbidity, mortality and transmission associated with undiagnosed and untreated infections. Rapid point-of-care tests that can detect multiple infections with a single fingerprick whole blood specimen using a single device are gaining popularity. We evaluated the field performance of a rapid dual HIV and syphilis test in people at high risk of HIV and syphilis infections. METHODS: Participants included men who have sex with men and transgender women recruited in Lima, Peru. Reference standard testing for detection of HIV and syphilis infections, conducted using blood samples from venipuncture, included Treponema pallidum particle agglutination and fourth-generation HIV enzyme immunoassay for which positive results had a confirmation HIV Western blot test. For the evaluation test, SD BIOLINE HIV/Syphilis Duo test (Standard Diagnostics, Korea), a fingerprick blood specimen was used. Sensitivity and specificity were calculated and the exact binomial method was used to determine 95% CIs. RESULTS: A total of 415 participants were recruited for the study. The dual test sensitivity for detection of T. pallidum infection was 89.2% (95% CI 83.5% to 93.5%) and specificity 98.8% (95% CI 96.5% to 99.8%). For detection of HIV infection, the sensitivity of the dual test was 99.1% (95% CI 94.8% to 100%) and specificity 99.4% (95% CI 97.7% to 99.9%). CONCLUSIONS: This high performing dual test should be considered for the use in clinical settings to increase uptake of simultaneous testing of HIV and syphilis and accelerate time to treatment for those who need it. PMID- 26670915 TI - Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice. AB - PURPOSE: Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted. METHODS: Data from two US private healthcare claims repositories were employed. The source population comprised adults who received "intermediate-risk" or "high-risk" chemotherapy regimens for solid cancers or non-Hodgkin's lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients") were matched (1:1) to those who received it ("pegfilgrastim patients") based on cancer, regimen, and propensity score. Odds ratios (OR) for FN-broad and narrow definitions-during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations. RESULTS: A total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2-2.5, p = 0.002) and 3.5 (95 % CI 2.0-6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis. PMID- 26670916 TI - Effectiveness of acupuncture in rehabilitation of physical and functional disorders of women undergoing breast cancer surgery. AB - PURPOSE: The purpose of the study is to verify the effectiveness of acupuncture in rehabilitation of physical and functional disorders of women undergoing breast cancer surgery on the following parameters: pain, range of motion, upper limb function, and depressive symptoms. METHODS: The following are the inclusion criteria: women aged more than 18 years with scapular girdle and upper limb pain after 3 months of surgery and with pain >=3 in visual analog scale. Patients were divided into two randomized groups which received weekly treatment during 10 sessions. Kinesiotherapy group (G1)-treated with a predefined kinesiotherapy protocol of 30 min. Group Acupuncture + Kinesiotherapy (G2)-treated with the same kinesiotherapy group protocol followed by another 30 min of acupuncture, used in predefined points. Both groups performed physical examination and answered the upper limb function and depressive symptoms questionnaires. RESULTS: Forty-eight patients completed the treatment, 24 in each group. Regarding the pain, the two groups had statistically significant improvement in all evaluated moments. In the analysis of depression, it improved significantly only in G1 in the comparison between the first and the tenth session. The upper limb function had improvement in G1 only in the comparison between the first and the tenth session and in G2, in the three evaluation moments. The range of motion (ROM) showed improvement in all evaluated movements. CONCLUSIONS: There was no difference between groups. Both groups showed statistically significant improvement of the items assessed: pain, depression, upper limb function, and ADM, and there was no difference between them. PMID- 26670917 TI - Effects of pre-radiation exposure to LLLT of normal and malignant cells. AB - PURPOSE: Low-level laser therapy (LLLT) efficacy for the prevention of cancer treatment-induced oral mucositis (OM) has been amply described. However, potential protection of malignant cells remains a legitimate concern for clinicians. We tested LLLT-induced protection from ionizing radiation killing in both malignant and normal cells. METHODS: We treated six groups each of normal human lymphoblasts (TK6) and human leukemia cells (HL60) with He-Ne LLLT (632.8 nm, 35 mW, CW, 1 cm(2), 35 mW/cm(2) for 3-343 s, 0.1-12 J/cm(2)) prior to exposure to ionizing radiation (IR). Cells were then incubated and counted daily to determine their survival. Optimization of IR dose and incubation time was established prior to testing the effect of LLLT. RESULTS: Growth curves for both cell lines showed significant declines after exposure to 50-200 cGy IR when compared to controls. Pre-radiation exposure to LLLT (4.0 J/cm(2)) followed by 1 h incubation blocked this decline in TK6 but not in HL60 cells. The latter cells were sensitized to the killing effects of IR in a dose-dependent manner. CONCLUSION: This study shows that pre-IR LLLT treatment results in a differential response of normal vs. malignant cells, suggesting that LLLT does not confer protection and may even sensitize cancer cells to IR killing. PMID- 26670918 TI - Correlation Between Platelet and Hemoglobin Levels and Pathological Characteristics and Prognosis of Early-Stage Squamous Cervical Carcinoma. AB - BACKGROUND We sought to determine the effect of pre-operative hemoglobin (HGB) and platelet (PLT) levels on the clinical features and prognosis of early-stage squamous cervical carcinoma (SCC). MATERIAL AND METHODS We performed a retrospective analysis of 380 patients with SCC who underwent hysterectomy and pelvic lymphadenectomy. SCC was confirmed post-operatively by pathological diagnosis. The relations between HGB and PLT levels and clinicopathological characteristics were observed, and a Cox regression analysis was performed to determine their influence on survival. RESULTS There were significant differences in tumor staging, tumor diameter, and lymphatic metastasis between the 69 patients with PLT levels >300*109/L and the 311 patients with PLT levels <=300*109/L (P<0.05). Tumor staging, extent of differentiation, and lymphatic metastasis were significantly different between 134 patients with HGB levels <120 g/L and 246 patients with HGB levels >=120 g/L (P<0.05). The overall survival rate in the group with PLT levels >300*109/L was lower than that in the group with PLT levels <=300 * 109/L, but this difference was not significant. The overall survival rate in the group with HGB levels <120 g/L was significantly lower than that in the group with HGB levels >=120 g/L (P<0.05), and the overall survival rate in the group with PLT levels >300*109/L and HGB levels <120 g/L was significantly lower than that in the group with PLT levels <=300*109/L and HGB levels <=120 g/L (P<0.05). According to Cox regression analysis, a pre-operative HGB level <120 g/L was considered a separate risk factor affecting prognosis. CONCLUSIONS Close attention must be paid to pre-operative PLT and HGB levels, and anemia should be remedied to facilitate the treatment of cervical carcinoma. PMID- 26670919 TI - Discovery and development of surotomycin for the treatment of Clostridium difficile. AB - The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6-25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin. PMID- 26670920 TI - Authorship: Few Myths and Misconceptions. AB - This article seeks to address and dispel some of the popular myths and misconceptions surrounding authorship of a scientific publication as this is often misconstrued by beginners in academia especially those in the developing world. While ethical issues in publishing related to authorship have been increasingly discussed, not much has been written about the myths and misconceptions of who might be an author. Dispelling these myths and misconceptions would go a long way in shaping the thoughts and plans of students, junior faculty and researchers in academia especially in the developing world. PMID- 26670921 TI - A review of dopamine agonist therapy in type 2 diabetes and effects on cardio metabolic parameters. AB - Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma. PMID- 26670922 TI - Spondyloepiphyseal Dysplasia Congenita in a painting of Vicente Lopez y Portana (1825). PMID- 26670923 TI - Intimate Partner Violence and Its Associated Factors in a Sample of Colombian Immigrant Population in Spain. AB - Immigrants are vulnerable to Intimate partner violence (IPV). This study aims at characterising IPV among Colombian immigrants, and to identify its associated factors. Cross-sectional study on 336 Colombian immigrants (46 % women), aged 15 70 years, living in Spain. Self-reported questionnaire information on IPV suffered throughout the last year was collected face-to-face. Multivariable logistic regression was used to identify factors associated with IPV. Almost 30 % of participants reported IPV, without differences by gender (p = 0.339). Partner's alcohol consumption was associated with a higher frequency of being victim of IPV in both sexes. In women, low educational level, and discrimination were further associated to IPV. Younger age, and poorer self-perceived health in Spain as compared to Colombia were factors associated in men. Results showed similarly high levels of IPV among immigrant men and women. Alcohol consumption, education, discrimination, age, and poor self-perceived health were factors associated to IPV. PMID- 26670924 TI - Angiopoietin-like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts. AB - KEY POINTS: Angiopoietin-like 4 (ANGPTL4) modulates tendon neovascularization. Cyclic loading stimulates the activity of transforming growth factor-beta and hypoxia-inducible factor 1alpha and thereby increases the expression and release of ANGPTL4 from human tendon cells. Targeting ANGPTL4 and its regulatory pathways is a potential avenue for regulating tendon vascularization to improve tendon healing or adaptation. ABSTRACT: The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-beta (TGF-beta) and hypoxia-inducible factor 1alpha (HIF-1alpha) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-beta and HIF-1alpha comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation. PMID- 26670925 TI - The impact of disturbed peatlands on river outgassing in Southeast Asia. AB - River outgassing has proven to be an integral part of the carbon cycle. In Southeast Asia, river outgassing quantities are uncertain due to lack of measured data. Here we investigate six rivers in Indonesia and Malaysia, during five expeditions. CO2 fluxes from Southeast Asian rivers amount to 66.9 +/- 15.7 Tg C per year, of which Indonesia releases 53.9 +/- 12.4 Tg C per year. Malaysian rivers emit 6.2 +/- 1.6 Tg C per year. These moderate values show that Southeast Asia is not the river outgassing hotspot as would be expected from the carbon enriched peat soils. This is due to the relatively short residence time of dissolved organic carbon (DOC) in the river, as the peatlands, being the primary source of DOC, are located near the coast. Limitation of bacterial production, due to low pH, oxygen depletion or the refractory nature of DOC, potentially also contributes to moderate CO2 fluxes as this decelerates decomposition. PMID- 26670927 TI - Temperature- and Pressure-Induced Spin Crossover in Co1+xCr2-xSe4 (x = 0.24): A Diffraction Study. AB - The Co(2+) ions of the Co1+xCr2-xSe4 phase (Co1.24Cr1.76Se4 composition with x = 0.24, C2/m space group, Cr3S4-type structure) undergo a high- to low-spin-state transition around 230 K, as concluded from the temperature-dependent single crystal synchrotron radiation diffraction experiments and the previously reported physical property studies. The change of the spin state is not instantaneous and goes through a wide spin-crossover (SCO) region of 75 K. A similar Co(2+) high- to low-spin-state transition is suggested at a pressure of 14.5 GPa, as is evident from the pressure-dependent single-crystal synchrotron radiation diffraction experiments. The corresponding SCO region is equal to 5 GPa, and the structural behavior is different from the one observed during the temperature dependent transition. Coupling between the spin-conversion process in Co1+xCr2 xSe4 and the concomitant changes in the physical properties opens a way for a controlled tuning of the observed physical response through compositional and structural modifications. PMID- 26670928 TI - In memoriam Dieter Falkenhagen (1942-2015): Pioneer, enthusiast, visionary. PMID- 26670926 TI - Cofilin as a Promising Therapeutic Target for Ischemic and Hemorrhagic Stroke. AB - Neurovascular unit (NVU) is considered as a conceptual framework for investigating the mechanisms as well as developing therapeutic targets for ischemic and hemorrhagic stroke. From a molecular perspective, oxidative stress, excitotoxicity, inflammation, and disruption of the blood brain barrier are broad pathophysiological frameworks on the basis on which potential therapeutic candidates for ischemic and hemorrhagic stroke could be discussed. Cofilin is a potent actin-binding protein that severs and depolymerizes actin filaments in order to generate the dynamics of the actin cytoskeleton. Although studies of the molecular mechanisms of cofilin-induced reorganization of the actin cytoskeleton have been ongoing for decades, the multicellular functions of cofilin and its regulation in different molecular pathways are expanding beyond its primary role in actin cytoskeleton. This review focuses on the role of cofilin in oxidative stress, excitotoxicity, inflammation, and disruption of the blood brain barrier in the context of NVU as well as how and why cofilin could be studied further as a potential target for ischemic and hemorrhagic stroke. PMID- 26670929 TI - Implementing the Xpert(r) MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries. AB - BACKGROUND: The Xpert(r) MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Medecins Sans Frontieres across varied geographic, epidemiological and clinical settings. METHODS: Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire. FINDINGS: In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support. CONCLUSION: The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed. PMID- 26670930 TI - Light Inhibition of Shoot Regeneration Is Regulated by Endogenous Abscisic Acid Level in Calli Derived from Immature Barley Embryos. AB - Shoot regeneration in calli derived from immature barley embryos is regulated by light conditions during the callus-induction period. Barley cultivars Kanto Nijo 5 (KN5) and K-3 (K3) showed lower efficiency of shoot regeneration in a 16-h photoperiod during callus-induction than those in continuous darkness, whereas shoot regeneration was enhanced in cultures under a 16-h photoperiod in Golden Promise (GP) and Lenins (LN). These cultivars were classified as photo-inhibition type (KN5 and K3) or photo-induction type (GP and LN) according to their response to light. Contents of endogenous plant hormones were determined in calli cultured under a 16-h photoperiod and continuous darkness. In photo-inhibition type, higher accumulation of abscisic acid (ABA) was detected in calli cultured under a 16-h photoperiod, whereas calli showed lower levels of endogenous ABA in continuous darkness. However, cultivars of photo-induction type showed lower levels of ABA in calli cultured under both light conditions, similarly to photo inhibition type in continuous darkness. Exogenous ABA inhibited the callus growth and shoot regeneration independent of light conditions in all cultivars. In photo inhibition type, lower levels of endogenous ABA induced by ABA biosynthesis inhibitor, fluridone, reduced the photo-inhibition of shoot regeneration. Expression of ABA biosynthesis gene, HvNCED1, in calli was regulated by the light conditions. Higher expression was observed in calli cultured under a 16-h photoperiod. These results indicate that ABA biosynthesis could be activated through the higher expression of HvNCED1 in a 16-h photoperiod and that the higher accumulations of ABA inhibit shoot regeneration in the photo-inhibition type cultivars. PMID- 26670931 TI - Biomimetic Taste Receptors with Chiral Recognition by Photoluminescent Metal Organic Frameworks Chelated with Polyaniline Helices. AB - The adsorption of phenylaniline (Phe) enantiomers on (+)-polyaniline (PAN) chelated [In(OH)(bdc)]n microcrystals was carefully designed and studied by using the Job titration, circular dichroism, X-ray photoelectron spectroscopy, and photoluminescence to mimic heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors in selective, but not specific, ligand binding with chiral recognition and signal transduction. Six essential working principles across different length scales are unraveled: 1) a chiral (+)-PAN (host), 2) specific sites for Phe-(+)/PAN (guest-host) binding, 3) a conformational change of (+)-PAN after binding with Phe enantiomers, 4) different degrees of packing for (+)-PAN, 5) interactions between (+)-PAN and the underlying signal-generating framework (i.e., [In(OH)(bdc)]n microcrystals), and 6) a systematic photoluminescent signal combination by using principal-component analysis from the other three polymer-chelated metal-organic frameworkds (MOFs), such as poly(acrylic acid) (PAA), sodium alginate (SA), and polyvinylpyrrolidone (PVP) to enhance the selectivity and discrimination capabilities. PMID- 26670932 TI - Aluminum Chloride Mediated Alkynylation of Boron Subphthalocyanine Chloride Using Trimethylsilyl-Capped Acetylenes. AB - A mild and versatile procedure is presented for functionalization of boron chloride subphthalocyanine at the axial boron position with trimethylsilyl protected alkyne nucleophiles in the presence of aluminum chloride. The method allows a large variety of substituents on the alkyne units, including electron donating/withdrawing aryl groups, silyl-protected alkynyl groups, as well as ferrocenyl and azulenyl groups. In addition, ferrocene itself reacts smoothly under these conditions allowing for directly anchoring it to the boron of the subphthalocyanine. PMID- 26670933 TI - The Effect of Palliative Care Team Design on Referrals to Pediatric Palliative Care. AB - BACKGROUND: The American Academy of Pediatrics (AAP) and the American Academy of Hospice and Palliative Medicine (AAHPM) have recommended minimal standards for palliative care (PC) team composition and availability. It is unknown whether team composition affects utilization of PC. OBJECTIVE: The study objective was to describe pediatric PC team composition, evaluate whether composition and availability are associated with utilization, and examine PC referral patterns. METHODS: The study was a descriptive survey. Subjects were pediatric PC team directors or hospital administrators at Pediatric Health Information System (PHIS) hospitals (N = 44). RESULTS: The overall response rate was 86%. Teams varied in size from <1 to 9 full-time members. Average referrals per hospital bed were 0.46, range 0.05-2.13. Among individual PC team roles, referral rates were 34% greater in teams with an advanced nurse practitioner (ANP) (p = 0.07). Likewise, teams with acute pain, chronic pain, or hospice palliative medicine specialists tended to have greater referral rates (39%, 36%, and 25%), though reported differences were not statistically significant. Teams adherent to the original AAP recommendations had a 31% greater referral rate (p = 0.22). Teams available 24 hours daily had similar referral rates to those with less availability (0.47 versus 0.46 [p = 0.94]). CONCLUSIONS: Team composition and availability are not crucial to PC utilization. Hospitals with some personnel but not all recommended team members should create formal teams and modify them over time. The addition of team members that tend to increase referrals, namely ANPs and acute pain, chronic pain, or hospice palliative medicine specialists, should be considered. PMID- 26670934 TI - Abstracts of papers presented at the 2015 UK Platelet Meeting held at the University of Leicester, 15-16 September 2015. PMID- 26670935 TI - Glabridin Alleviates the Toxic Effects of Methylglyoxal on Osteoblastic MC3T3-E1 Cells by Increasing Expression of the Glyoxalase System and Nrf2/HO-1 Signaling and Protecting Mitochondrial Function. AB - Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes associated complications. The present study investigated the effects of glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings suggest that glabridin protects against MG-induced cell damage by inhibiting oxidative stress and increasing MG detoxification. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin reduced MG-induced mitochondrial dysfunction. Additionally, the nitric oxide level significantly increased upon glabridin pretreatment. Together, these data show that glabridin may potentially serve to prevent the development of diabetic bone disease associated with MG-induced oxidative stress. PMID- 26670936 TI - Comparison of Two Parathyroid Hormone Assays in Hemodialysis Patients. AB - Parathyroid hormone (PTH) determination is essential for the diagnosis of renal osteodystrophy, but differences between the laboratory assays can lead to different therapies. This study compared the new Tosoh ST AIA-Pack Intact PTH assay (Tosoh Bioscience, San Francisco, CA, USA) with the Elecsys Intact PTH Roche assay (Roche Diagnostics GmbH, Mannheim, Germany), currently considered the gold standard. Nineteen chronic stable hemodialysis patients were enrolled to check PTH levels with the two assays. Median age was 71 years (range 26-84), M/F = 10/9. Blood samples were taken before the start of the same midweek dialysis session. Two blood vacuettes were collected and immediately transported to the central laboratory. The median PTH value was 268 (range 35-901 pg/dL) with the AIA-Pack versus 184 (range 39-552 pg/dL) with Elecsys. The Wilcoxon test showed a significant difference between the two methods (P < 0.0001). AIA-Pack showed a delta value of +38% in comparison with Elecsys and a median bias of 27.4%. For PTH values <150 pg/dL, nine patients were detected with AIA-Pack (47.4%) versus nine patients detected with Elecsys (47.4%). For PTH values between 150 and 300 pg/dL, six patients were detected with AIA-Pack (31.6%) versus four patients with Elecsys (21.0%). For PTH values >300 pg/dL four patients were detected with AIA Pack (21.0%) versus six patients with Elecsys (31.6%). The two assays showed no differences for each of the three PTH ranges considered. The two PTH assays tested are different and the attending physician should be aware of the differences when patients change their dialysis facility. PMID- 26670937 TI - Effects of Pregnancy on Papillary Microcarcinomas of the Thyroid Re-Evaluated in the Entire Patient Series at Kuma Hospital. AB - BACKGROUND: An active-surveillance clinical trial of low-risk papillary microcarcinoma (PMC) patients has been performed at the authors' institution, Kuma Hospital, since 1993. Favorable oncological results have been reported. During the trial, a few patients were encountered with PMC that showed enlargement during pregnancy, and these cases have been reported. During pregnancy, a large amount of human chorionic gonadotropin (hCG) having weak thyrotropin (TSH) activity is produced, possibly affecting the progression of PMC. This study investigated how pregnancy and delivery influenced the progression of PMC in the entire active surveillance PMC patient series. METHODS: From 1993 to 2013, 1841 patients with low-risk PMC chose the active surveillance program. Fifty of the 1549 female PMC patients experienced 51 pregnancies/deliveries. To minimize observer variation, a single specialist sonographer re-evaluated the changes in the size of these 50 patients' PMCs before and after the pregnancies/deliveries. RESULTS: Four patients (8%) showed enlargement of PMC by >=3 mm; one patient (2%) showed a decrease by >=3 mm, and the remaining 44 patients (45 events, 90%) showed stable disease. None of the patients had a novel appearance of lymph node metastases during pregnancy. Of the four patients with enlargement, two underwent surgery after delivery, and the other two continued the active surveillance, since their tumors did not grow after the delivery. After delivery, the PMC of one of these four patients remained stable, and another showed a decrease in PMC size. To date, six more PMC patients underwent surgery after delivery for reasons other than disease progression due to pregnancy and delivery: two opted out of active surveillance, two were identified with a nodal metastasis during active surveillance after delivery, one had Graves' disease, and one showed enlargement of nodules of the contralateral lobe. CONCLUSIONS: Pregnancy and delivery was associated with an increase in size of PMCs in only 8% of the 51 pregnancies/delivery cases. None of the patients developed nodal metastasis during pregnancy. Thus, a possible future pregnancy does not prevent such patients from undergoing active surveillance, although watchful observation during pregnancy is recommended. PMID- 26670938 TI - How Does the Fast Track Intervention Prevent Adverse Outcomes in Young Adulthood? AB - Numerous studies have shown that childhood interventions can foster improved outcomes in adulthood. Less well understood is precisely how-that is, through which developmental pathways-these interventions work. This study assesses mechanisms by which the Fast Track project (n = 891), a randomized intervention in the early 1990s for high-risk children in four communities (Durham, NC; Nashville, TN; rural PA; and Seattle, WA), reduced delinquency, arrests, and general and mental health service utilization in adolescence through young adulthood (ages 12-20). A decomposition of treatment effects indicates that about a third of Fast Track's impact on later crime outcomes can be accounted for by improvements in social and self-regulation skills during childhood (ages 6-11), such as prosocial behavior, emotion regulation, and problem solving. These skills proved less valuable for the prevention of general and mental health problems. PMID- 26670939 TI - Nanoscale Kerr Nonlinearity Enhancement Using Spontaneously Generated Coherence in Plasmonic Nanocavity. AB - The enhancement of the optical nonlinear effects at nanoscale is important in the on-chip optical information processing. We theoretically propose the mechanism of the great Kerr nonlinearity enhancement by using anisotropic Purcell factors in a double-Lambda type four-level system, i.e., if the bisector of the two vertical dipole moments lies in the small/large Purcell factor axis in the space, the Kerr nonlinearity will be enhanced/decreased due to the spontaneously generated coherence accordingly. Besides, when the two dipole moments are parallel, the extremely large Kerr nonlinearity increase appears, which comes from the double population trapping. Using the custom-designed resonant plasmonic nanostructure which gives an anisotropic Purcell factor environment, we demonstrate the effective nanoscale control of the Kerr nonlinearity. Such controllable Kerr nonlinearity may be realized by the state-of-the-art nanotechnics and it may have potential applications in on-chip photonic nonlinear devices. PMID- 26670940 TI - Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates. AB - Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5-1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries. PMID- 26670941 TI - Seventy years of continuous encroachment substantially increases 'blue carbon' capacity as mangroves replace intertidal salt marshes. AB - Shifts in ecosystem structure have been observed over recent decades as woody plants encroach upon grasslands and wetlands globally. The migration of mangrove forests into salt marsh ecosystems is one such shift which could have important implications for global 'blue carbon' stocks. To date, attempts to quantify changes in ecosystem function are essentially constrained to climate-mediated pulses (30 years or less) of encroachment occurring at the thermal limits of mangroves. In this study, we track the continuous, lateral encroachment of mangroves into two south-eastern Australian salt marshes over a period of 70 years and quantify corresponding changes in biomass and belowground C stores. Substantial increases in biomass and belowground C stores have resulted as mangroves replaced salt marsh at both marine and estuarine sites. After 30 years, aboveground biomass was significantly higher than salt marsh, with biomass continuing to increase with mangrove age. Biomass increased at the mesohaline river site by 130 +/- 18 Mg biomass km(-2) yr(-1) (mean +/- SE), a 2.5 times higher rate than the marine embayment site (52 +/- 10 Mg biomass km(-2) yr(-1) ), suggesting local constraints on biomass production. At both sites, and across all vegetation categories, belowground C considerably outweighed aboveground biomass stocks, with belowground C stocks increasing at up to 230 +/- 62 Mg C km(-2) yr( 1) (+/- SE) as mangrove forests developed. Over the past 70 years, we estimate mangrove encroachment may have already enhanced intertidal biomass by up to 283 097 Mg and belowground C stocks by over 500 000 Mg in the state of New South Wales alone. Under changing climatic conditions and rising sea levels, global blue carbon storage may be enhanced as mangrove encroachment becomes more widespread, thereby countering global warming. PMID- 26670942 TI - Spectroscopic Evidence for Clusters of Like-Charged Ions in Ionic Liquids Stabilized by Cooperative Hydrogen Bonding. AB - Direct spectroscopic evidence for hydrogen-bonded clusters of like-charged ions is reported for ionic liquids. The measured infrared O-H vibrational bands of the hydroxyethyl groups in the cations can be assigned to the dispersion-corrected DFT calculated frequencies of linear and cyclic clusters. Compensating the like charge Coulomb repulsion, these cationic clusters can range up to cyclic tetramers resembling molecular clusters of water and alcohols. These ionic clusters are mainly present at low temperature and show strong cooperative effects in hydrogen bonding. DFT-D3 calculations of the pure multiply charged clusters suggest that the attractive hydrogen bonds can compete with repulsive Coulomb forces. PMID- 26670943 TI - Protein kinase G signaling in cardiac pathophysiology: Impact of proteomics on clinical trials. AB - The protective role of cyclic guanosine monophosphate (cGMP)-stimulated protein kinase G (PKG) in the heart makes it an attractive target for therapeutic drug development to treat a variety of cardiac diseases. Phosphodiesterases degrade cGMP, thus phosphodiesterase inhibitors that can increase PKG are of translational interest and the subject of ongoing human trials. PKG signaling is complex, however, and understanding its downstream phosphorylation targets and upstream regulation are necessary steps toward safe and efficacious drug development. Proteomic technologies have paved the way for assays that allow us to peer broadly into signaling minutia, including protein quantity changes and phosphorylation events. However, there are persistent challenges to the proteomic study of PKG, such as the impact of the expression of different PKG isoforms, changes in its localization within the cell, and alterations caused by oxidative stress. PKG signaling is also dependent upon sex and potentially the genetic and epigenetic background of the individual. Thus, the rigorous application of proteomics to the field will be necessary to address how these effectors can alter PKG signaling and interfere with pharmacological interventions. This review will summarize PKG signaling, how it is being targeted clinically, and the proteomic challenges and techniques that are being used to study it. PMID- 26670944 TI - IL-6 Antibody and RGD Peptide Conjugated Poly(amidoamine) Dendrimer for Targeted Drug Delivery of HeLa Cells. AB - In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5 RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells. PMID- 26670945 TI - Introducing MDM Policy & Practice. PMID- 26670946 TI - Physiological response to elevated temperature and pCO2 varies across four Pacific coral species: Understanding the unique host+symbiont response. AB - The physiological response to individual and combined stressors of elevated temperature and pCO2 were measured over a 24-day period in four Pacific corals and their respective symbionts (Acropora millepora/Symbiodinium C21a, Pocillopora damicornis/Symbiodinium C1c-d-t, Montipora monasteriata/Symbiodinium C15, and Turbinaria reniformis/Symbiodinium trenchii). Multivariate analyses indicated that elevated temperature played a greater role in altering physiological response, with the greatest degree of change occurring within M. monasteriata and T. reniformis. Algal cellular volume, protein, and lipid content all increased for M. monasteriata. Likewise, S. trenchii volume and protein content in T. reniformis also increased with temperature. Despite decreases in maximal photochemical efficiency, few changes in biochemical composition (i.e. lipids, proteins, and carbohydrates) or cellular volume occurred at high temperature in the two thermally sensitive symbionts C21a and C1c-d-t. Intracellular carbonic anhydrase transcript abundance increased with temperature in A. millepora but not in P. damicornis, possibly reflecting differences in host mitigated carbon supply during thermal stress. Importantly, our results show that the host and symbiont response to climate change differs considerably across species and that greater physiological plasticity in response to elevated temperature may be an important strategy distinguishing thermally tolerant vs. thermally sensitive species. PMID- 26670948 TI - Ion beam nanopatterning of III-V semiconductors: consistency of experimental and simulation trends within a chemistry-driven theory. AB - Several proposed mechanisms and theoretical models exist concerning nanostructure evolution on III-V semiconductors (particularly GaSb) via ion beam irradiation. However, making quantitative contact between experiment on the one hand and model parameter dependent predictions from different theories on the other is usually difficult. In this study, we take a different approach and provide an experimental investigation with a range of targets (GaSb, GaAs, GaP) and ion species (Ne, Ar, Kr, Xe) to determine new parametric trends regarding nanostructure evolution. Concurrently, atomistic simulations using binary collision approximation over the same ion/target combinations were performed to determine parametric trends on several quantities related to existing model. A comparison of experimental and numerical trends reveals that the two are broadly consistent under the assumption that instabilities are driven by chemical instability based on phase separation. Furthermore, the atomistic simulations and a survey of material thermodynamic properties suggest that a plausible microscopic mechanism for this process is an ion-enhanced mobility associated with energy deposition by collision cascades. PMID- 26670947 TI - Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood. AB - BACKGROUND: Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. METHOD: One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. RESULTS: During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship. CONCLUSIONS: Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes. PMID- 26670949 TI - Management of Obstructive Sleep Apnea and Comorbid Insomnia: A Mixed-Methods Evaluation. AB - The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research. PMID- 26670950 TI - Study of thermal conductivity of ice clusters after impact deposition on the silica surfaces using the ReaxFF reactive force field. AB - During aircraft or spacecraft missions, ice accumulates on different parts of their surface elements. An important parameter affecting the ability to remove this ice from the surface is the heat transfer characteristics of the accumulated ice. The ice heat transfer is related to the process of ice formation and its density and internal structure. In this study we investigate the effects of the ice and silica structure and the ice cluster attachment mechanism to the silica surface on the thermal conductivity (TC) of the attached ice cluster using the ReaxFF reactive force field. The purpose of this study is to investigate the thermal transport in amorphous and crystalline ice after high-velocity deposition on the silica surfaces. A dual thermostat method has been applied for the calculation of TC values. The validity of this method has been verified by comparing the calculated values of TC for crystal and amorphous ice with available experimental values. Our calculations show that the TC values of both crystal and amorphous ice drop after deposition on the silica surfaces. This decrease in the TC is more significant for the ice deposition on suboxide silica surfaces. Furthermore, crystal ice shows higher TC values than amorphous ice after accumulation. However, when crystal ice impacts on the silica surface at 1 km s(-1) impact speed, the crystalline shape of the ice cluster is lost to a considerable level and the TC values obtained for the ice clusters in such cases are closer to amorphous ice TC values. We observed a decrease in the TC values when ionic species are added inside the ice clusters. PMID- 26670951 TI - Amnion Epithelial Cells of Buffalo (Bubalus Bubalis) Term Placenta Expressed Embryonic Stem Cells Markers and Differentiated into Cells of Neurogenic Lineage In Vitro. AB - Aim of the present study was the isolation, culture, and characterization of amniotic membrane-derived epithelial cells (AE) from term placenta collected postpartum in buffalo. We found that cultured cells were of polygonal in shape, resistance to trypsin digestion and expressed cytokeratin-18 indicating that they were of epithelial origin. These cells have negative expression of mesenchymal stem cell markers (CD29, CD44, and CD105) and positive for pluripotency marker (OCT4) genes indicated that cultured cells were not contaminated with mesenchymal stem cells. Immunofluorescence staining with pluripotent stem cell surface markers, SSEA-1, SSEA-4, TRA-1-60, and TRA-1-81 indicated that these cells may retain pluripotent stem cell characteristics even after long period of differentiation. Differentiation potential of these cells was determined by their potential to differentiate into cells of neurogenic lineages using retinoic acid. In conclusion, we demonstrate that AE cells expressed pluripotent stem cell markers and have propensity to differentiate into cells of neurogenic lineage upon directed differentiation in vitro. PMID- 26670953 TI - Lysyl oxidase promotes epithelial-to-mesenchymal transition during paraquat induced pulmonary fibrosis. AB - Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays a critical role in pulmonary fibrosis. Our previous study demonstrated that epithelial-to mesenchymal transition (EMT) was strongly associated with paraquat (PQ) induced pulmonary fibrosis. This present study was aimed to evaluate the potential involvement of LOX on EMT in the process of pulmonary fibrosis induced by PQ. We established an in vivo rat model and an in vitro cell model induced by PQ treatment and found that LOX protein expression was significantly up-regulated and collagen deposition was enhanced in rats. The EMT process was strongly found in A549 and RLE-6TN cells after PQ exposure. After inactivating LOX with an inhibitor, pulmonary fibrosis was significantly reduced and EMT was also suppressed. Additionally, small interfering RNA (siRNA) targeting LOX was used to silence LOX expression to observe EMT in A549 cells. As a result, LOX could promote the progress of EMT, and inactivating LOX alleviated the EMT process in PQ-induced pulmonary fibrosis and mesenchymal-to-epithelial transition (MET) occurred after inactivating LOX in vitro and in vivo. In conclusion, LOX could promote the progress of EMT and inactivating LOX alleviated EMT in PQ-induced pulmonary fibrosis. Therefore, LOX could potentially be a new candidate therapeutic target for pulmonary fibrosis induced by PQ by regulating the balance between EMT and MET. PMID- 26670952 TI - A Novel Inhibitor Prevents the Peripheral Neuroparalysis of Botulinum Neurotoxins. AB - Botulinum neurotoxins (BoNTs) form a large class of potent and deadly neurotoxins. Given their growing number, it is of paramount importance to discover novel inhibitors targeting common steps of their intoxication process. Recently, EGA was shown to inhibit the action of bacterial toxins and viruses exhibiting a pH-dependent translocation step in mammalian cells, by interfering with their entry route. As BoNTs act in the cytosol of nerve terminals, the entry into an appropriate compartment wherefrom they translocate the catalytic moiety is essential for toxicity. Herein we propose an optimized procedure to synthesize EGA and we show that, in vitro, it prevents the neurotoxicity of different BoNT serotypes by interfering with their trafficking. Furthermore, in mice, EGA mitigates botulism symptoms induced by BoNT/A and significantly decreases the lethality of BoNT/B and BoNT/D. This opens the possibility of using EGA as a lead compound to develop novel inhibitors of botulinum neurotoxins. PMID- 26670954 TI - Role of Second Transplantation for Children With Acute Myeloid Leukemia Following Posttransplantation Relapse. AB - BACKGROUND: In children with acute myeloid leukemia (AML), hematopoietic stem cell transplantation (HSCT) in first remission is indicated for patients with a relatively high risk of relapse. Second HSCT is a curative option; however, few reports have been published about a second HSCT in children for AML with posttransplantation relapse. PROCEDURE: Using the database provided by the Japanese Society of Hematopoietic Cell Transplantation, we analyzed 46 children with AML who underwent a second allogeneic HSCT after achieving a second remission. RESULTS: The median duration from the first to second HSCT was 20 months, and the source of the second HSCT was related bone marrow (BM) in 22, related peripheral blood in 6, unrelated BM in 14, and unrelated cord blood in 4 patients. Twenty-five children eventually died of the following causes: progressive disease in 14 and transplant-related toxicities in 9. The 5-year overall survival rate was 41.7 +/- 7.7%. An interval of less than 24 months between the first and second HSCT was a significant poor prognostic factor. CONCLUSIONS: Children with AML who experience a relapse after HSCT in first remission have a good chance of survival with a second HSCT if a second remission is achieved. PMID- 26670955 TI - NiSi(x)/a-Si Nanowires with Interfacial a-Ge as Anodes for High-Rate Lithium-Ion Batteries. AB - Conductive metal nanowire is a promising current collector for the Si-based anode material in high-rate lithium-ion batteries. However, to harness this remarkable potential for high power density energy storage, one has to address the interfacial potential barrier that hinders the electron injection from the metal side. Herein, we present that, solely by inserting ultrathin amorphous germanium (a-Ge) (~5 nm) at the interface of NiSix/amorphous Si (a-Si), the rate capacity was substantially enhanced, 477 mAh g(-1) even at a high rate of 40 A g(-1). In addition, batteries containing the NiSix/Ge+Si anodes cycled over 1000 times at 10 A g(-1) while the capacity retaining more than 877 mAh g(-1), which is among the highest reported. The excellent electrochemical performance is directly correlated with the significantly improved electrical conductivity and mechanical stability throughout the entire electrode. The potential barrier between the NiSix and a-Si was modulated by a-Ge, which constructs an electron highway. Besides, the a-Ge interlayer enhances the interfacial adhesion by reducing void fraction and the inhomogeneous strain of the Li-Ge and Li-Si stacking structure was accommodated through the bending and twist of relatively thin NiSix, thus ensures a more stable high-rate cycling performance. Our work shows an effective way to fabricate metal/a-Si nanowires for high-rate lithium-ion battery anodes. PMID- 26670958 TI - Le Discret (The Silence): Joseph Ducreux. PMID- 26670959 TI - Can Hospitals Help Create Healthy Neighborhoods? PMID- 26670967 TI - Choosing a Health Insurance Plan: Complexity and Consequences. PMID- 26670968 TI - A PIECE OF MY MIND. From Shame to Guilt to Love. PMID- 26670969 TI - Alternating Electric Fields for the Treatment of Glioblastoma. PMID- 26670970 TI - Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial. AB - IMPORTANCE: Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. OBJECTIVE: To evaluate the effect of autologous HSCT on refractory Crohn disease. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. INTERVENTIONS: All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. MAIN OUTCOMES AND MEASURES: Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. RESULTS: Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died. CONCLUSIONS AND RELEVANCE: Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00297193. PMID- 26670972 TI - Management of Graves Disease: A Review. AB - IMPORTANCE: Graves disease is the most common cause of persistent hyperthyroidism in adults. Approximately 3% of women and 0.5% of men will develop Graves disease during their lifetime. OBSERVATIONS: We searched PubMed and the Cochrane database for English-language studies published from June 2000 through October 5, 2015. Thirteen randomized clinical trials, 5 systematic reviews and meta-analyses, and 52 observational studies were included in this review. Patients with Graves disease may be treated with antithyroid drugs, radioactive iodine (RAI), or surgery (near-total thyroidectomy). The optimal approach depends on patient preference, geography, and clinical factors. A 12- to 18-month course of antithyroid drugs may lead to a remission in approximately 50% of patients but can cause potentially significant (albeit rare) adverse reactions, including agranulocytosis and hepatotoxicity. Adverse reactions typically occur within the first 90 days of therapy. Treating Graves disease with RAI and surgery result in gland destruction or removal, necessitating life-long levothyroxine replacement. Use of RAI has also been associated with the development or worsening of thyroid eye disease in approximately 15% to 20% of patients. Surgery is favored in patients with concomitant suspicious or malignant thyroid nodules, coexisting hyperparathyroidism, and in patients with large goiters or moderate to severe thyroid eye disease who cannot be treated using antithyroid drugs. However, surgery is associated with potential complications such as hypoparathyroidism and vocal cord paralysis in a small proportion of patients. In pregnancy, antithyroid drugs are the primary therapy, but some women with Graves disease opt to receive definitive therapy with RAI or surgery prior to becoming pregnant to avoid potential teratogenic effects of antithyroid drugs during pregnancy. CONCLUSIONS AND RELEVANCE: Management of Graves disease includes treatment with antithyroid drugs, RAI, or thyroidectomy. The optimal approach depends on patient preference and specific patient clinical features such as age, history of arrhythmia or ischemic heart disease, size of goiter, and severity of thyrotoxicosis. Physicians should be familiar with the advantages and disadvantages of each therapy to best counsel their patients. PMID- 26670973 TI - What Does This Retina Examination Show? PMID- 26670971 TI - Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. AB - IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7 25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409. PMID- 26670974 TI - Hormonal Evaluation of Hyperandrogenism in Women. PMID- 26670975 TI - Trends in National Institutes of Health Funding for Clinical Trials Registered in ClinicalTrials.gov. PMID- 26670976 TI - Pioglitazone Use and Risk of Bladder Cancer. PMID- 26670977 TI - Pioglitazone Use and Risk of Bladder Cancer. PMID- 26670978 TI - Pioglitazone Use and Risk of Bladder Cancer--Reply. PMID- 26670979 TI - Fresh vs Cryopreserved Donor Oocytes. PMID- 26670980 TI - Wording Errors in the Text. PMID- 26670981 TI - Clarification of Reporting Programs. PMID- 26670982 TI - Fresh vs Cryopreserved Donor Oocytes--Reply. PMID- 26670984 TI - The Madness of Sport. PMID- 26670985 TI - JAMA PATIENT PAGE. Safe and Healthy International Travel. PMID- 26670986 TI - Short-Term Effects of Different Loading Schemes in Fitness-Related Resistance Training. AB - Eifler, C. Short-term effects of different loading schemes in fitness-related resistance training. J Strength Cond Res 30(7): 1880-1889, 2016-The purpose of this investigation was to analyze the short-term effects of different loading schemes in fitness-related resistance training and to identify the most effective loading method for advanced recreational athletes. The investigation was designed as a longitudinal field-test study. Two hundred healthy mature subjects with at least 12 months' experience in resistance training were randomized in 4 samples of 50 subjects each. Gender distribution was homogenous in all samples. Training effects were quantified by 10 repetition maximum (10RM) and 1 repetition maximum (1RM) testing (pre-post-test design). Over a period of 6 weeks, a standardized resistance training protocol with 3 training sessions per week was realized. Testing and training included 8 resistance training exercises in a standardized order. The following loading schemes were randomly matched to each sample: constant load (CL) with constant volume of repetitions, increasing load (IL) with decreasing volume of repetitions, decreasing load (DL) with increasing volume of repetitions, daily changing load (DCL), and volume of repetitions. For all loading schemes, significant strength gains (p < 0.001) could be noted for all resistance training exercises and both dependent variables (10RM, 1RM). In all cases, DCL obtained significantly higher strength gains (p < 0.001) than CL, IL, and DL. There were no significant differences in strength gains between CL, IL, and DL. The present data indicate that resistance training following DCL is more effective for advanced recreational athletes than CL, IL, or DL. Considering that DCL is widely unknown in fitness-related resistance training, the present data indicate, there is potential for improving resistance training in commercial fitness clubs. PMID- 26670987 TI - The Effect of Compression Stockings on Physiological and Psychological Responses after 5-km Performance in Recreationally Active Females. AB - Treseler, C, Bixby, WR, and Nepocatych, S. The effect of compression stockings on physiological and psychological responses after 5-Km performance in recreationally active females. J Strength Cond Res 30(7): 1985-1991, 2016-The purpose of the study was to examine the physiological and perceptual responses to wearing below-the-knee compression stockings (CS) after a 5-km running performance in recreationally active women. Nineteen women were recruited to participate in the study (20 +/- 1 year, 61.4 +/- 5.3 kg, 22.6 +/- 3.9% body fat). Each participant completed two 5-km performance time trials with CS or regular socks in a counterbalanced order separated by 1 week. For each session, 5 km time, heart rate (HR), rate of perceived exertion (RPE), pain pressure threshold, muscle soreness (MS), and rate of perceived recovery were measured. There was no significant difference in average 5-km times between CS and regular socks (p = 0.74) and HR response (p = 0.42). However, significantly higher RPE and lower gain scores (%) for lower extremity MS but not for calf were observed with CS when compared with regular socks (p = 0.05, p = 0.01, and p = 0.3, respectively). Based on the results of this study, there were no significant improvements in average 5-km running time, heart rate, or perceived calf MS. However, participants perceived less MS in lower extremities and working harder with CS compared with regular socks. Compression stockings may not cause significant physiological improvements; however, there might be psychological benefits positively affecting postexercise recovery. PMID- 26670988 TI - Tapering Practices of New Zealand's Elite Raw Powerlifters. AB - Pritchard, HJ, Tod, DA, Barnes, MJ, Keogh, JW, and McGuigan, MR. Tapering practices of New Zealand's elite raw powerlifters. J Strength Cond Res 30(7): 1796-1804, 2016-The major aim of this study was to determine tapering strategies of elite powerlifters. Eleven New Zealand powerlifters (28.4 +/- 7.0 years, best Wilks score of 431.9 +/- 43.9 points) classified as elite were interviewed, using semistructured interviews, about their tapering strategies. Interviews were transcribed verbatim and content analyzed. Total training volume peaked 5.2 +/- 1.7 weeks from competition while average training intensity (of 1 repetition maximum) peaked 1.9 +/- 0.8 weeks from competition. During tapering, volume was reduced by 58.9 +/- 8.4% while intensity was maintained (or slightly reduced) and the final weight training session was performed 3.7 +/- 1.6 days out from competition. Participants generally stated that tapering was performed to achieve full recovery; that accessory work was removed around 2 weeks out from competition; and deadlifting takes longer to recover from than other lifts. Typically participants stated that trial and error, and changes based on "feel" were the sources of tapering strategies; equipment used and movements performed during tapering are the same as in competition; nutrition was manipulated during the taper (for weight cutting or performance aims); and poor tapering occurred when too long (1 week or more) was taken off training. These results suggest that athletes may benefit from continuing to strength train before important events with reduced volume and maintained intensity. Only exercises that directly assist sports performance should remain in the strength program during tapering, to assist with reductions in fatigue while maintaining/improving strength expression and performance. PMID- 26670989 TI - Effects of In-Season Inertial Resistance Training With Eccentric Overload in a Sports Population at Risk for Patellar Tendinopathy. AB - Gual, G, Fort-Vanmeerhaeghe, A, Romero-Rodriguez, D, and Tesch, PA. Effects of in season inertial resistance training with eccentric overload in a sports population at risk for patellar tendinopathy. J Strength Cond Res 30(7): 1834 1842, 2016-Volleyball and basketball players can be considered as a population at risk for patellar tendinopathy. Given the paradox that eccentric training elicits therapeutic benefits yet might provoke such injury, we investigated the influence of a weekly bout of inertial squat resistance exercise offering eccentric overload on lower limb muscle power and patellar tendon complaints. Players of 8 (4 basketball and 4 volleyball) teams (38 women and 43 men) were randomly assigned to either the intervention (IG) or control (CG) group. Although IG and CG maintained scheduled in-season training routines over 24 weeks, IG, in addition, performed 1 weekly session of eccentric overload by 4 sets of 8 repetitions of the squat using flywheel inertial resistance. Victorian Institute of Sports Assessment patellar tendinopathy questionnaire (VISA-p), vertical countermovement jump, and squat power, both concentric (Squat-Con) and eccentric (Squat-Ecc), tests were performed before (T1), during (T2), and after (T3) the 24 weeks of intervention. Neither group suffered from patellar tendinopathy during the study period. VISA-p displayed no differences across groups at any measurement period. Countermovement jump scores significantly (p <= 0.05) differed between groups in favor of the IG. Both Squat-Con and Squat-Ecc mean scores from the IG were significantly (p < 0.01) higher than the CG. Adding a weekly eccentric overload squat training bout to a regular basketball and volleyball exercise routine enhances lower limb muscle power without triggering patellar tendon complaints. Future studies, using the current exercise paradigm, aim to explore its efficacy to prevent or combat patellar tendinopathy in sports calling for frequent explosive jumps. PMID- 26670990 TI - Potentiation: Effect of Ballistic and Heavy Exercise on Vertical Jump Performance. AB - Hester, GM, Pope, ZK, Sellers, JH, Thiele, RM, and DeFreitas, JM. Potentiation: Effect of ballistic and heavy exercise on vertical jump performance. J Strength Cond Res 31(3): 660-666, 2017-The purpose of this study was to compare the acute effects of heavy and ballistic conditioning protocols on vertical jump performance in resistance-trained men. Fourteen resistance-trained men (mean +/- SD: age = 22 +/- 2.1 years, body mass = 86.29 +/- 9.95 kg, and height = 175.39 +/ 9.34 cm) with an average relative full squat of 2.02 +/- 0.28 times their body mass participated in this study. In randomized, counterbalanced order, subjects performed two countermovement vertical jumps before and 1, 3, 5, and 10 minutes after either performing 10 rapid jump squats or 5 heavy back squats. The back squat protocol consisted of 5 repetitions at 80% one repetition maximum (1RM), whereas the jump squat protocol consisted of 10 repetitions at 20% 1RM. Peak jump height (in centimeters) using a jump mat, along with power output (in Watts) and velocity (in meters per second) through a linear transducer, was recorded for each time interval. There was no significant condition * time interaction for any of the dependent variables (p = 0.066-0.127). In addition, there was no main effect for condition for any of the dependent variables (p = 0.457-0.899). Neither the ballistic nor heavy protocol used in this study enhanced vertical jump performance at any recovery interval. The use of these protocols in resistance-trained men to produce postactivation potentiation is not recommended. PMID- 26670991 TI - Small Beneficial Effect of Caffeinated Energy Drink Ingestion on Strength. AB - Collier, NB, Hardy, MA, Millard-Stafford, ML, and Warren, GL. Small beneficial effect of caffeinated energy drink ingestion on strength. J Strength Cond Res 30(7): 1862-1870, 2016-Because caffeine ingestion has been found to increase muscle strength, our aim was to determine whether caffeine when combined with other potential ergogenic ingredients, such as those in commercial energy drinks, would have a similar effect. Fifteen young healthy subjects were used in a double blind, repeated-measures experimental design. Each subject performed 3 trials, ingesting either a caffeinated energy drink, an uncaffeinated version of the drink, or a placebo drink. The interpolated twitch procedure was used to assess maximum voluntary isometric contraction (MVIC) strength, electrically evoked strength, and percent muscle activation during MVIC of the knee extensors both before and after drink ingestion, and after a fatiguing bout of contractions; electromyographic (EMG) amplitude of the knee extensors during MVIC was also assessed. The mean (+/-SE) change in MVIC strength from before to after drink ingestion was significantly greater for the caffeinated energy drink compared with placebo [+5.0 (+/-1.7) vs. -0.5 (+/-1.5)%] and the difference between the drinks remained after fatigue (p = 0.015); the strength changes for the uncaffeinated energy drink were not significantly different from those of the other 2 drinks at any time. There was no significant effect of drink type on the changes in electrically evoked strength, percent muscle activation, and EMG from before to after drink ingestion. This study indicates that a caffeinated energy drink can increase MVIC strength but the effect is modest and the strength increase cannot be attributed to increased muscle activation. Whether the efficacy of energy drinks can be attributed solely to caffeine remains unclear. PMID- 26670992 TI - Comparison of Resistance Exercise Perceived Exertion and Muscle Activation at Varied Submaximal Durations, Loads, and Muscle Actions. AB - Hollander, DB, Worley, JR, Asoodeh, M, Wakesa, D, Magnuson, M, Dantzler, DK, Didier, JJ, and Kraemer, RR. Comparison of resistance exercise perceived exertion and muscle activation at varied submaximal durations, loads, and muscle actions. J Strength Cond Res 31(5): 1387-1394, 2017-Previous studies investigating muscle activation from dynamic, plate-loaded, concentric (CON) and eccentric (ECC) muscle contractions have not accounted for the greater absolute strength of ECC contractions. The purpose of the study was to determine the effect of different dynamic muscle contraction durations, loads, and contraction types (CON and ECC) on perceived exertion and muscle activation differences in 6 women (mean +/- SD age, height, weight, body mass index 22.83 +/- 2.56 years, 1.65 +/- 0.261 m, 68.56 +/- 2.72 kg, 25.26 +/- 4.39 kg.m). The participants were recruited and trained to move weight at the appropriate duration (2, 3, 4, and 5 seconds) for leg extension using a displacement apparatus (sonic emitter, auditory) and a computer program (visual feedback of bar displacement). Concentric and ECC 1 repetition maximum (1RM) were determined for leg extension for the midrange 3 second duration. Thirty, 50, and 70% of either CON or ECC 1RM were loaded for the remainder of the sessions. Subjects were then assigned to complete trials in a counterbalanced fashion for load, contraction type, and contraction duration. Rating of perceived exertion (RPE) significantly increased in response to load (30, 50, and 70%) regardless of contraction type as did electromyography (EMG) root mean square amplitude. Greater time under tension significantly increased RPE regardless of contraction type during knee extension exercise. The EMG amplitude was less distinguishable between 2, 3, 4, and 5 seconds of contractions. The data highlight the effort sense distinctions made by women at submaximal exercise loads during knee extension. These findings should be used to develop effective resistance exercise protocols that facilitate positive perceptions and adherence resistance exercise loads, durations of contraction, and contraction type. PMID- 26670993 TI - Validity and Reliability of the PUSH Wearable Device to Measure Movement Velocity During the Back Squat Exercise. AB - Balsalobre-Fernandez, C, Kuzdub, M, Poveda-Ortiz, P, and Campo-Vecino, Jd. Validity and reliability of the PUSH wearable device to measure movement velocity during the back squat exercise. J Strength Cond Res 30(7): 1968-1974, 2016-The purpose of this study was to analyze the validity and reliability of a wearable device to measure movement velocity during the back squat exercise. To do this, 10 recreationally active healthy men (age = 23.4 +/- 5.2 years; back squat 1 repetition maximum [1RM] = 83 +/- 8.2 kg) performed 3 repetitions of the back squat exercise with 5 different loads ranging from 25 to 85% 1RM on a Smith Machine. Movement velocity for each of the total 150 repetitions was simultaneously recorded using the T-Force linear transducer (LT) and the PUSH wearable band. Results showed a high correlation between the LT and the wearable device mean (r = 0.85; standard error of estimate [SEE] = 0.08 m.s) and peak velocity (r = 0.91, SEE = 0.1 m.s). Moreover, there was a very high agreement between these 2 devices for the measurement of mean (intraclass correlation coefficient [ICC] = 0.907) and peak velocity (ICC = 0.944), although a systematic bias between devices was observed (PUSH peak velocity being -0.07 +/- 0.1 m.s lower, p <= 0.05). When measuring the 3 repetitions with each load, both devices displayed almost equal reliability (Test-retest reliability: LT [r = 0.98], PUSH [r = 0.956]; ICC: LT [ICC = 0.989], PUSH [ICC = 0.981]; coefficient of variation [CV]: LT [CV = 4.2%], PUSH [CV = 5.0%]). Finally, individual load-velocity relationships measured with both the LT (R = 0.96) and the PUSH wearable device (R = 0.94) showed similar, very high coefficients of determination. In conclusion, these results support the use of an affordable wearable device to track velocity during back squat training. Wearable devices, such as the one in this study, could have valuable practical applications for strength and conditioning coaches. PMID- 26670994 TI - Potentiation Following Ballistic and Nonballistic Complexes: The Effect of Strength Level. AB - Suchomel, TJ, Sato, K, DeWeese, BH, Ebben, WP, and Stone, MH. Potentiation following ballistic and nonballistic complexes: the effect of strength level. J Strength Cond Res 30(7): 1825-1833, 2016-The purpose of this study was to compare the temporal profile of strong and weak subjects during ballistic and nonballistic potentiation complexes. Eight strong (relative back squat = 2.1 +/- 0.1 times body mass) and 8 weak (relative back squat = 1.6 +/- 0.2 times body mass) males performed squat jumps immediately and every minute up to 10 minutes following potentiation complexes that included ballistic or nonballistic concentric-only half-squat (COHS) performed at 90% of their 1 repetition maximum COHS. Jump height (JH) and allometrically scaled peak power (PPa) were compared using a series of 2 * 12 repeated measures analyses of variance. No statistically significant strength level main effects for JH (p = 0.442) or PPa (p = 0.078) existed during the ballistic condition. In contrast, statistically significant main effects for time existed for both JH (p = 0.014) and PPa (p < 0.001); however, no statistically significant pairwise comparisons were present (p > 0.05). Statistically significant strength level main effects existed for PPa (p = 0.039) but not for JH (p = 0.137) during the nonballistic condition. Post hoc analysis revealed that the strong subjects produced statistically greater PPa than the weaker subjects (p = 0.039). Statistically significant time main effects existed for time existed for PPa (p = 0.015), but not for JH (p = 0.178). No statistically significant strength level * time interaction effects for JH (p = 0.319) or PPa (p = 0.203) were present for the ballistic or nonballistic conditions. Practical significance indicated by effect sizes and the relationships between maximum potentiation and relative strength suggest that stronger subjects potentiate earlier and to a greater extent than weaker subjects during ballistic and nonballistic potentiation complexes. PMID- 26670995 TI - Comparisons: Technical-Tactical and Time-Motion Analysis of Mixed Martial Arts by Outcomes. AB - Miarka, B, Vecchio, FBD, Camey, S, and Amtmann, JA. Comparisons: technical tactical and time-motion analysis of mixed martial arts by outcomes. J Strength Cond Res 30(7): 1975-1984, 2016-The aim of this study was to compare time-motion and technical-tactical analysis between paired outcomes and rounds of mixed martial arts (MMA) matches. The sample consisted of 645 rounds of MMA competition paired by outcomes (first round, winners n = 215 and losers n = 215; second round, winners n = 215 and losers n = 215; third round, winners n = 215 and losers n = 215). The time-motion variables were categorized into low-intensity or high-intensity, stand-up or groundwork situations. Stand-up techniques were analyzed by observing total strikes to the head and body, and takedowns. The actions on the ground were analyzed by observing submission activity, including successful choking and joint locking actions, and also positional improvements, including advances to the mount, half guard, and side and back positions. Chi squared and Wilcoxon tests were conducted with a significance level of p <= 0.05. Results showed that winners had higher values for total strikes and submissions in all rounds, and also positional improvements, over losers. The standing combat with low-intensity comparisons presented differences between the rounds first, with a median of 2:33.5 (P25-P75%: 1:20-3:56) minute, second, with 2:37 (1:24 3:59) minute, and third, with 2:07 (1:06-3:39.2) minute. These data suggest a focus on the intermittent demand presented in combat phases with a special attention to the strike and ground technical-tactical skills; strength and conditioning coaches could emphasize the effort pause ratios for both standing and ground combat that mimic the requirements of MMA, especially during the third round. PMID- 26670996 TI - Greater electromyographic responses do not imply greater motor unit recruitment and 'hypertrophic potential' cannot be inferred. PMID- 26670997 TI - Reply to: idiopathic 'Half and half' nails. PMID- 26670998 TI - Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis. AB - Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes. Upon target contact, the CTL centrosome rapidly moves to the immunological synapse, focusing microtubule-directed release at this point [1-3]. Striking similarities have been noted between centrosome polarization at the synapse and basal body docking during ciliogenesis [1, 4-8], suggesting that CTL centrosomes might dock with the plasma membrane during killing, in a manner analogous to primary cilia formation [1, 4]. However, questions remain regarding the extent and function of centrosome polarization at the synapse, and recent reports have challenged its role [9, 10]. Here, we use high-resolution transmission electron microscopy (TEM) tomography analysis to show that, as in ciliogenesis, the distal appendages of the CTL mother centriole contact the plasma membrane directly during synapse formation. This is functionally important as small interfering RNA (siRNA) targeting of the distal appendage protein, Cep83, required for membrane contact during ciliogenesis [11], impairs CTL secretion. Furthermore, the regulatory proteins CP110 and Cep97, which must dissociate from the mother centriole to allow cilia formation [12], remain associated with the mother centriole in CTLs, and neither axoneme nor transition zone ciliary structures form. Moreover, complete centrosome docking can occur in proliferating CTLs with multiple centriole pairs. Thus, in CTLs, centrosomes dock transiently with the membrane, within the cell cycle and without progression into ciliogenesis. We propose that this transient centrosome docking without cilia formation is important for CTLs to deliver rapid, repeated polarized secretion directed by the centrosome. PMID- 26670999 TI - A Class of Visual Neurons with Wide-Field Properties Is Required for Local Motion Detection. AB - Visual motion cues are used by many animals to guide navigation across a wide range of environments. Long-standing theoretical models have made predictions about the computations that compare light signals across space and time to detect motion. Using connectomic and physiological approaches, candidate circuits that can implement various algorithmic steps have been proposed in the Drosophila visual system. These pathways connect photoreceptors, via interneurons in the lamina and the medulla, to direction-selective cells in the lobula and lobula plate. However, the functional architecture of these circuits remains incompletely understood. Here, we use a forward genetic approach to identify the medulla neuron Tm9 as critical for motion-evoked behavioral responses. Using in vivo calcium imaging combined with genetic silencing, we place Tm9 within motion detecting circuitry. Tm9 receives functional inputs from the lamina neurons L3 and, unexpectedly, L1 and passes information onto the direction-selective T5 neuron. Whereas the morphology of Tm9 suggested that this cell would inform circuits about local points in space, we found that the Tm9 spatial receptive field is large. Thus, this circuit informs elementary motion detectors about a wide region of the visual scene. In addition, Tm9 exhibits sustained responses that provide a tonic signal about incoming light patterns. Silencing Tm9 dramatically reduces the response amplitude of T5 neurons under a broad range of different motion conditions. Thus, our data demonstrate that sustained and wide field signals are essential for elementary motion processing. PMID- 26671000 TI - In Reply. PMID- 26671002 TI - Family and cultural influences on cervical cancer screening among immigrant Latinas in Miami-Dade County, USA. AB - Cervical cancer disproportionately affects minorities, immigrants and low-income women in the USA, with disparities greatest among Latino immigrants. We examined barriers and facilitators to cervical cancer screening practices among a group of immigrant Latino women in Florida, USA. Between January and May 2013, six focus group discussions, involving 35 participants, were conducted among Hispanic women in Miami to explore their knowledge, beliefs about cervical cancer and facilitators and barriers to cervical cancer screening using a theoretical framework. The data showed that family support, especially from female relatives, was an important facilitator of screening and treatment. Women, however, reported prioritising family health over their own, and some expressed fatalistic beliefs about cancer. Major obstacles to receiving a Pap smear included fear that it might result in removal of the uterus, discomfort about being seen by a male doctor and concern that testing might stigmatise them as being sexually promiscuous or having a sexually transmitted disease. Targeted education on cancer and prevention is critically needed in this population. Efforts should focus on women of all ages since younger women often turn to older female relatives for advice. PMID- 26671001 TI - Asymmetric Response of Costa Rican White-Breasted Wood-Wrens (Henicorhina leucosticta) to Vocalizations from Allopatric Populations. AB - Divergence in song between allopatric populations can contribute to premating reproductive isolation in territorial birds. Song divergence is typically measured by quantifying divergence in vocal traits using audio recordings, but field playback experiments provide a more direct way to behaviorally measure song divergence between allopatric populations. The White-breasted Wood-Wren (Henicorhina leucosticta; hereafter "WBWW") is an abundant Neotropical species with four mitochondrial clades (in Central America, the Darien, the Choco and the Amazon) that are deeply divergent (~5-16% sequence divergence). We assessed the possibility that the WBWW as currently defined may represent multiple biological species by conducting both statistical analysis of vocal characters and field playback experiments within three clades (Central America, Choco and Amazon). Our analysis of vocal traits revealed that Central American songs overlapped in acoustic space with Choco songs, indicating vocal similarity between these two populations, but that Central American songs were largely divergent from Amazonian songs. Playback experiments in the Caribbean lowlands of Costa Rica revealed that Central American WBWWs typically responded aggressively to songs from the Choco population but did not respond to playback of songs from the Amazonian population, echoing the results of the vocal trait analysis. This marked difference in behavioral response demonstrates that the songs of Central American and Amazonian WBWWs (but not Central American and Choco WBWWs) have diverged sufficiently that Central American WBWWs no longer recognize song from Amazonian WBWWs as a signal to elicit territorial defense. This suggests that significant premating reproductive isolation has evolved between these two populations, at least from the perspective of the Central American population, and is consistent with the possibility that Central American and Amazonian populations represent distinct biological species. We conclude by advocating for the further use of field playback experiments to assess premating reproductive isolation (and species limits) between allopatric songbird populations, a situation where behavioral systematics can answer questions that phylogenetic systematics cannot. PMID- 26671003 TI - Herbal and nutrient complementary medicines for weight loss: community pharmacists' practices, attitudes, recommendations, information and education needs. AB - OBJECTIVES: To investigate pharmacists' herbal/nutrient weight loss complementary medicine (WLCM) practices in the context of other pharmacist weight management support practices (provision of lifestyle advice, orlistat and meal replacement treatments); and gain insight into their attitudes, recommendations, information and education needs. METHODS: Pharmacists from a randomly selected sample of 214 community pharmacies from different socioeconomic areas in the Greater Brisbane region, Australia, were invited to complete a survey to explore their weight management practices, with a specific focus on herbal/nutrient WLCM practices. Data collected from the sample group represented pharmacist practices within the metropolitan Greater Brisbane region. KEY FINDINGS: This survey achieved a 51% response rate. During weight management consultations, a high proportion of customers (37%) sought advice from community pharmacists relating to WLCMs relative to other weight management practices; however, only a small proportion (10%) of pharmacists recommended them. Most were also found to be using resources that may not be evidence-based or do not provide sufficient WLCMs' information. CONCLUSION: Study results highlight the need for pharmacy professional bodies to develop evidence-based continuing education programmes to assist consumers with popular and widely available WLCMs products. PMID- 26671004 TI - Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries. AB - We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP) containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20ug/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries. PMID- 26671005 TI - Treatment effect of l-Norvaline on the sexual performance of male rats with streptozotocin induced diabetes. AB - Sexual impairment is an established risk factor in diabetes mellitus affecting about 75% of male diabetic population. In diabetes overexpression of arginase leads to decreased production of NO and diminished erectile response. Inhibition of arginase enzyme can lead to improvement in diabetes induced sexual dysfunction. In the present study diabetes mellitus was induced in adult male rats by intraperitoneal injection of single dose of streptozotocin (65mg/kg) in 0.1M Citrate buffer pH 4.5 and after 72h fasting serum glucose level was checked by glucose oxidase-peroxidase method and those animals showing FSG above 250mg/dl were selected. Diabetic animals were divided into four groups comprising six animals in each. l-Norvaline, potent arginase inhibitor was administered at a dose of 10mg/kg ip to the different groups of diabetic animals for a period of 30 days. Sildenafil at a dose of 5mg/kg orally was used as a standard drug. Mating behavior tests were performed at 0, 15th and 30th days. After 30 days, various biochemical and hormonal parameters (nitrates, LDH, urea, testosterone), testicular parameters (total protein, nitrates, LDH, total cholesterol, LDL, triglycerides, VLDL, HDL) were evaluated to find out the effect of l-Norvaline in sexual impairment. Sperm analysis was also carried out for the treated rats. l Norvaline showed significant improvement in serum nitrates, urea, LDH, testosterone and testicular protein level as compared with diabetic group. It also improved sperm motility, count and viability in diabetic rats. Sildenafil showed no improvement in above parameters except restoration in serum nitrates level. PMID- 26671006 TI - Exogenous testosterone increases men's perceptions of their own physical dominance. AB - Men's testosterone is associated with several constructs that are linked to dominance rank, such as risk-taking, mating success, and aggression. However, no study has directly tested the relationship between men's self-perceived dominance and testosterone using an experimental design. We employed a within-subjects, double-blind, placebo-controlled paradigm to assess whether testosterone influences men's self-perceived dominance. Exogenous testosterone or a placebo was administered to healthy adult men and self-perceptions of physical dominance were subsequently assessed by having participants select what they believed to be their true face from an array of images digitally manipulated in masculinity. Men picked a more masculine version of their own face after testosterone versus placebo--an effect that was particularly pronounced among men with relatively low baseline testosterone. These findings indicate that a single administration of testosterone can rapidly modulate men's perceptions of their own physical dominance, which may explain links between testosterone and dominance-related behaviors. PMID- 26671007 TI - Oxytocin improves compassion toward women among patients with PTSD. AB - Although impairments in social skills, including empathic abilities, are common in post-traumatic stress disorder (PTSD), the ability to feel compassion-a pro social behavior that is based on empathy and drives us to help others-has never been assessed among these patients. The first aim of this study was to examine whether patients with PTSD suffer from deficits in compassion and to examine the association between the clusters of PTSD symptoms and these deficits. Furthermore, given that intranasal oxytocin (OT) has been suggested to possibly modulate social behaviors, the second aim of this study was to investigate whether intranasal OT may enhance compassion in these patients. Using a randomized, double-blind, placebo-controlled crossover design, we administered 24 IU of OT and placebo at a one-week interval to 32 patients with PTSD and to 30 matched healthy control participants. The results indicate that patients with PTSD exhibit deficits in compassion and that the numbing cluster emerged as the key predictor of those deficits. Moreover, the results indicate that a single intranasal dose of OT enhances compassion toward women (but not towards men), both in patients with PTSD and in controls. These results offer support for recent suggestions that intranasal OT may potentially be an effective pharmacological intervention for patients with PTSD. PMID- 26671008 TI - [Epidemiological profile of traumatic brain injury at the Dr. Rafael A. Calderon Guardia Hospital, Neurosurgery Department, during the period from 2007 to 2012]. AB - OBJECTIVE: To determine the epidemiological profile of the patients who suffered traumatic brain injury (TBI) and were treated at the Dr. Rafael A. Calderon Guardia Hospital (HCG) Neurosurgery department, during the period from 2007 to 2012. MATERIAL AND METHODS: An observational, descriptive, retrospective and cross section study was performed on all the patients with TBI and who were admitted to the emergency room of the HCG during the period 2007 to 2012. There were a total of 721 cases, of which 566 records were obtained of patients who had the variables established in this study, excluding those with incomplete or inconsistent information. RESULTS: The present study established the epidemiological profile of the TBI in the population seen during the period 2007 to 2012 at the HCG. It was determined that the male sex made up the majority of the cases were male, with mean age of 46 years. The mortality rate was 12.69% (n=69). Car accidents were the most frequent cause of TBI (n=259 persons) in the age group of 25 to 44 years, followed by falls (n=174). It was observed that the majority were farmers, followed by students, and then construction workers. No chronic illnesses were recorded in 71.6% of the medical charts. No alcohol or other drugs were reported in 74.9% of the cases, while there was evidence of the presence of alcohol recorded in 22.8%. The clinical and laboratory parameters that had statistical significance (P<.05) were GCS equal to less than 8 (P=.035), presence of mydriasis (P=.00), deviation of the LM (P=.006), cranial fracture (P=.04), lack of endotracheal intubation on admission (P=.007), prolonged PT (P=.04), prolonged PTT (P=.025), and MAP<60 (P=.002). The most frequent surgical procedure in the study population was craniotomy with hematoma drainage alone or associated with some other procedure (esquillectomy or monitoring of PIC) (n=298). CONCLUSIONS: There is great difficulty in determining the epidemiology of TBI worldwide, due to the lack of standardisation of the international studies. From the present study, it can be concluded that the population that mainly suffers from this type of lesion are adults under 45 years old, with car accidents being the main cause of these lesions (45.8%) in combination with alcohol consumption. Also, the consequences of such are aggravated when the victims present with chronic diseases such as, systemic arterial hypertension and mellitus diabetes. As regards the post-traumatic indicators directly related to a poor outcome, it was determined that a GCS score equal to or less than 8, a mean blood pressure less than 60, the prolongation of the coagulation times, the presence of mydriasis, and skull fractures, have a direct association with the negative or fatal outcome for the victim. PMID- 26671009 TI - [High-grade glioma after stereotactic radiosurgery for vestibular schwannoma]. AB - Stereotactic radiosurgery undoubtedly represents an important therapeutic procedure for various intracranial pathologies, especially tumours, although they are not entirely complication-free. Radiosurgery have been considered a good management strategy for the majority of small-to-medium size vestibular schwannomas. The authors describe a case of high-grade glioma associated with a previous radiosurgery treatment for a vestibular schwannoma in a 69 year-old woman. A detailed description of these cases is provided, as well as a summary of the related literature. PMID- 26671010 TI - Construction and optimization of an efficient amplification method of a random ssDNA library by asymmetric emulsion PCR. AB - Construction of a random ssDNA sublibrary is an important step of the aptamer screening process. The available construction methods include asymmetric PCR, biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR amplification is a key step. The main drawback of PCR amplification is overamplification increasing nonspecific hybridization among different products and by-products, which may cause the loss of potential high-quality aptamers, inefficient screening, and even screening failure. Cycle number optimization in PCR amplification is the main way to avoid overamplification but does not fundamentally eliminate the nonspecific hybridization, and the decreased cycle number may lead to insufficient product amounts. Here, we developed a new method, "asymmetric emulsion PCR," which could overcome the shortcomings of conventional PCR. In asymmetric emulsion PCR, different templates were separated by emulsion particles, allowing single-molecule PCR, in which each template was separately amplified, and the nonspecific hybridization was avoided. Overamplification or formation of by-products was not observed. The method is so simple that direct amplification of 40 or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric emulsion PCR would improve the screening efficiency of systematic evolution of ligands by exponential enrichment. PMID- 26671011 TI - A more practical way to place a correct Poller (blocking) screw. PMID- 26671013 TI - Correction: Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals. PMID- 26671012 TI - Burden of malaria among adult patients attending general medical outpatient department and HIV care and treatment clinics in Oromia, Ethiopia: a comparative cross-sectional study. AB - BACKGROUND: Malaria and HIV/AIDS constitute major public health problems in Ethiopia, but the burden associated with malaria-HIV co-infection has not been well documented. In this study, the burden of malaria among HIV positive and HIV negative adult outpatients attending health facilities in Oromia National Regional State, Ethiopia was investigated. METHODS: A comparative cross-sectional study among HIV-positive patients having routine follow-up visits at HIV care and treatment clinics and HIV-seronegative patients attending the general medical outpatient departments in 12 health facilities during the peak malaria transmission season was conducted from September to November, 2011. A total of 3638 patients (1819 from each group) were enrolled in the study. Provider initiated testing and counseling of HIV was performed for 1831 medical outpatients out of whom 1819 were negative and enrolled into the study. Malaria blood microscopy and hemoglobin testing were performed for all 3638 patients. Data was analyzed using descriptive statistics, Chi square test and multivariate logistic regression. RESULTS: Of the 3638 patients enrolled in the study, malaria parasitaemia was detected in 156 (4.3%); malaria parasitaemia prevalence was 0.7% (13/1819) among HIV-seropositive patients and 7.9% (143/1819) among HIV seronegative patients. Among HIV-seropositive individuals 65.4% slept under a mosquito bed net the night before data collection, compared to 59.4% of HIV seronegative individuals. A significantly higher proportion of HIV-seropositive malaria-negative patients were on co-trimoxazole (CTX) prophylaxis as compared to HIV-malaria co-infected patients: 82% (1481/1806) versus 46% (6/13) (P = 0.001). HIV and malaria co-infected patients were less likely to have the classical symptoms of malaria (fever, chills and headache) compared to the HIV-seronegative and malaria positive counterparts. Multivariate logistic regression showed that HIV-seropositive patients who come for routine follow up were less likely to be infected by malaria (OR = 0.23, 95% CI = 0.09-0.74). CONCLUSION: The study documented lower malaria prevalence among the HIV-seropositive attendants who come for routine follow up. Clinical symptoms of malaria were more pronounced among HIV-seronegative than HIV-seropositive patients. This study also re affirmed the importance of co-trimoxazole in preventing malaria symptoms and parasitaemia among HIV-positive patients. PMID- 26671014 TI - Cancer's Darwinian dilemma: an evolutionary tale in three acts. PMID- 26671015 TI - Long-Term Management of RAP Lesions in Clinical Practice: Treatment Efficacy and Predictors of Functional Improvement. AB - PURPOSE: To evaluate the long-term efficacy of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) and to identify predictors of functional outcome. METHODS: Retrospective case series comprised 79 eyes of 68 consecutive patients with RAP followed up >=36 months. Primary end-points were best-corrected visual acuity (BCVA) and central macular thickness (CMT) variation at 36 months and at the last visit. RESULTS: Mean follow-up time was 59.8 +/- 16.0 months. All eyes were treated with pro re nata ranibizumab, with (n = 33) or without (n = 46) photodynamic therapy (PDT). Stabilization or improvement in BCVA was observed in 50.6% of the patients at 36 months, and in 40.5% at the end of the follow-up, where 20.3% preserved reading vision. A significant decrease in CMT was observed at 36 months (p < 0.001), but not at the end of the follow-up. Geographic atrophy (GA) was present in 59.5% of the eyes at the final visit. Baseline subretinal fluid was associated with better visual outcomes (p = 0.001). Results of combination treatment with intravitreal ranibizumab and PDT did not significantly differ from ranibizumab monotherapy. CONCLUSION: Modest functional outcomes can be expected from the long-term treatment of RAP lesions in clinical practice, most likely due to the advent of GA. Baseline subretinal fluid positively correlated with final BCVA. PMID- 26671016 TI - The diagnostic challenge of very early-onset enterocolitis in an infant with XIAP deficiency. AB - BACKGROUND: Aggressive course and resistance to treatments usually characterize very early onset inflammatory bowel disease (VEO-IBD). Some VEO-IBD cases are due to monogenic immune defects and can benefit from hematopoietic stem cell transplantation (HSCT). CASE PRESENTATION: We describe a Caucasian male baby who presented in the first months of life macrophage activation syndrome, followed by intractable colitis, recurrent episodes of fever and mild splenomegaly. After several immunological, genetic and clinical investigations, subsequently a therapeutic attempt with colectomy, analysis of VEO-IBD-associated genes, revealed a causative mutation in XIAP. The genetic diagnosis of a primary immune deficiency allowed curing the boy with hematopoietic stem cell transplantation. CONCLUSION: Our report, together with novel findings from recent literature, should contribute to increase awareness of monogenic immune defects as a cause of VEO-IBD. Comprehensive genetic analysis can allow a prompt diagnosis, resulting in the choice of effective treatments and sparing useless and damaging procedures. PMID- 26671017 TI - Differences in antibiotic use between patients with and without a regular doctor in Hong Kong. AB - BACKGROUND: Literature shows that continuity of care from a primary care physician is associated with better patient satisfaction and preventive care. This may also have an effect on patients' use of antibiotics. This study investigated the differences in antibiotic use between patients with and without a regular doctor in a pluralistic health care system. METHODS: A cross-sectional telephone questionnaire survey using randomly selected household phone numbers was conducted in Hong Kong. Several key areas about antibiotic use were compared between the respondents with a regular doctor and those without. RESULTS: The response rate was 68.3 %. Of the 2,471 respondents, 1,450 (58.7 %) had a regular doctor, 942 (38.1 %) without, and 79 (3.2 %) did not give a clear answer. The respondents with a regular doctor were more likely to report that they always finished the full course of antibiotics (74.2 % vs 62.4 %), as well as using antibiotics for their last upper respiratory tract infections (17.4 % vs 10.1 %). The association with antibiotic use remained significant in the multivariable logistic regression analysis after adjusting for other confounding factors (P < 0.001, OR = 1.76, 95 % CI:(1.27, 2.48)). CONCLUSIONS: While patients with a regular doctor, compared to those without, were more likely to report finishing the full course of antibiotics, they also had nearly twice the chance of reporting antibiotic use for upper respiratory tract infections. This challenges the common belief of the benefits in having a regular doctor. PMID- 26671018 TI - Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock. AB - INTRODUCTION: Septic shock is one of the most frequent causes of admission to the intensive care unit (ICU) and is associated with a poor prognosis. Early and late death in septic shock should be distinguished because they may involve different underlying mechanisms. In various conditions, the neutrophil-to-lymphocyte count ratio (NLCR) has been described as an easily measurable parameter to express injury severity. In the present study, we investigated whether the timing of death was related to a particular NLCR. METHODS: We conducted a prospective, single-center, observational study that included consecutive septic shock patients. Severity scores, early (before day 5) or late (on or after day 5 of septic shock onset) ICU mortality, and daily leukocyte counts were collected during the ICU stay. We assessed the association between leukocyte counts at admission and their evolution during the first 5 days with early or late death. The association between patient characteristics (including cell counts) and prognosis was estimated using Cox proportional cause-specific hazards models. RESULTS: The study included 130 patients who were diagnosed with abdominal (n = 99) or extra-abdominal (n = 31) septic shock. The median (interquartile range) NLCR was 12.5 (6.5-21.2) in survivors and 6.2 (3.7-12.6) in nonsurvivors (p = 0.001). The NLCR at admission was significantly lower in patients who died before day 5 than in survivors (5 [3.5-11.6] versus 12.5 [6.5-21.2], respectively; p = 0.01). From day 1 to day 5, an increased NLCR related to an increase in neutrophil count and a decrease in lymphocyte count was associated with late death (+34.8 % [-8.2 to 305.4] versus -20 % [-57.4 to 45.9]; p = 0.003). Those results were present in patients with abdominal origin sepsis as well as in those with extra-abdominal sepsis, who were analyzed separately. CONCLUSIONS: In the present study, a reversed NLCR evolution was observed according to the timing of death. Septic shock patients at risk of early death had a low NLCR at admission, although late death was associated with an increased NLCR during the first 5 days. PMID- 26671019 TI - Association of Jumping Mechanography-Derived Indices of Muscle Function with Tibial Cortical Bone Geometry. AB - Jumping mechanography has been developed to estimate maximum voluntary muscle forces. This study assessed associations of jumping mechanography-derived force and power measurements with tibial cortical bone geometry, compared to other estimates of muscle mass, size, and function. Healthy men (n = 181; 25-45 years) were recruited in a cross-sectional, population-based sibling-pair study. Muscle parameters include isokinetic peak torque of the quadriceps, DXA-derived leg lean mass, mechanography-derived peak jump force and power, and pQCT-derived mid tibial (66 %) muscle cross-sectional area (CSA). Mid-tibial cortical bone parameters were assessed by pQCT. In age, height, and weight-adjusted analyses, jump force and power correlated positively with cortical bone area, cortical thickness, and polar strength-strain index (SSIp) (beta = 0.23-0.34, p <= 0.001 for force; beta = 0.25-0.30, p <= 0.007 for power) and inversely with endosteal circumference adjusted for periosteal circumference (ECPC) (beta = -0.16, p < 0.001 for force; beta = -0.13, p = 0.007 for power). Force but not power correlated with cortical over total bone area ratio (beta = 0.25, p = 0.002). Whereas leg lean mass correlated with all cortical parameters except cortical over total bone area ratio (beta = 0.25-0.62, p <= 0.004), muscle CSA only correlated with cortical bone area, periosteal circumference, and SSIp (beta = 0.21-0.26, p <= 0.001), and quadriceps torque showed no significant correlations with the bone parameters. Multivariate models indicated that leg lean mass was independently associated with overall bone size and strength reflected by periosteal and endosteal circumference and SSIp (beta = 0.32-0.55, p <= 0.004), whereas jump force was independently associated with cortical bone size reflected by ECPC, cortical thickness, and cortical over total bone area ratio (beta = 0.13 0.28; p <= 0.002). These data indicate that jumping mechanography provides relevant information about the relationship of muscle with bone geometry. PMID- 26671020 TI - Orofacial-cervical alterations in individuals with upper airway resistance syndrome. AB - INTRODUCTION: Studies that assess the upper airways in sleep-related breathing disorders have been performed only in patients with obstructive sleep apnea syndrome who seek medical attention. Therefore, in addition to the need for population studies, there are no data on the orofacial-cervical physical examination in subjects with upper airway resistance syndrome. OBJECTIVES: To compare the orofacial-cervical examination between volunteers with upper airway resistance syndrome and without sleep-related breathing disorders. METHODS: Through questionnaires, physical measurements, polysomnography, and otorhinolaryngological evaluation, this study compared the orofacial-cervical physical examination, through a systematic analysis of the facial skeleton, mouth, throat, and nose, between volunteers with upper airway resistance syndrome and volunteers without sleep-related breathing disorders in a representative sample of the adult population of the city of Sao Paulo. RESULTS: There were 1042 volunteers evaluated; 49 subjects (5%) were excluded as they did not undergo otorhinolaryngological evaluation, 381 (36%) had apnea-hypopnea index>5 events/hour, and 131 (13%) had oxyhemoglobin saturation<90%. Among the remaining 481 subjects (46%), 30 (3%) met the criteria for the upper airway resistance syndrome definition and 53 (5%) met the control group criteria. At the clinical evaluation of nasal symptoms, the upper airway resistance syndrome group had more oropharyngeal dryness (17% vs. 29.6%; p=0.025) and septal deviation grades 1-3 (49.1% vs. 57.7%; p=0.025) when compared to controls. In the logistic regression model, it was found that individuals from the upper airway resistance syndrome group had 15.6-fold higher chance of having nose alterations, 11.2-fold higher chance of being hypertensive, and 7.6-fold higher chance of complaining of oropharyngeal dryness when compared to the control group. CONCLUSION: Systematic evaluation of the facial skeleton, mouth, throat, and nose, between volunteers with upper airway resistance syndrome and volunteers without sleep-related breathing disorders, showed that the presence of upper airway resistance syndrome is mainly associated with nasal alterations and oropharyngeal dryness, in addition to the risk of hypertension, regardless of gender and obesity. PMID- 26671021 TI - The learning progression of diagnostic sialendoscopy. AB - INTRODUCTION: Sialendoscopy is becoming the gold standard procedure for diagnosis and treatment of Salivary Gland Inflammatory Diseases. OBJECTIVE: To evaluate the learning progression of a single surgeon to implement and perform diagnostic sialendoscopy: to estimate how many procedures were necessary to achieve better results; if it was higher rate of complications in the beginning. METHODS: Retrospective analysis involving 113 consecutive sialendoscopies performed from 2010 to 2013. According to a descriptive analysis of the factors related to surgeon's experience, the casuistic was divided into two groups: group (A) comprising the first 50 exams, and group (B) the last 63. Groups were then compared concerning demographic and peri-operative aspects. RESULTS: In Group A, failure to catheterize papilla were 22% versus 3% in B (p=0.001). Failure to complete examination was 30% in group A versus 6% in B (p=0.001), and necessity to repeat exams was 22% in group A versus 10% in B (p=0.058). The complication rates were 18% in group A, and 10% in B (p=0.149). Operative time was slightly shorter in group B (56 versus 41 min, p=0.045). CONCLUSION: We found better outcomes after the first 50 diagnostic sialendoscopies. Complication rates were statistically the same between early and late groups of experience with sialendoscopy. PMID- 26671022 TI - Function of obturator prosthesis after maxillectomy and prosthetic obturator rehabilitation. AB - INTRODUCTION: Maxillary defects are usually rehabilitated by a prosthetic obturator. OBJECTIVE: This study aimed to evaluate the functioning of obturators prosthesis in patients with unilateral defects after maxillectomy. METHODS: Of 49 patients, 28 underwent to maxillectomy as a result of tumor ablative surgery, and acquired unilateral maxillary defects. Evaluation of the function was performed by applying the Obturator Functional Scale (OFS). RESULTS: From a total of 49 patients, 28 were treated as follows: 9 with a conventional retained obturator prosthesis (COP), 11 (39%) with an enhanced retentive obturator prosthesis with stud attachment (POP) and 8 (28%) with an enhanced retentive obturator prosthesis with magnetic attachment (POM). The mean OFS score was 80. Scores on functions of speech, swallowing and chewing reached statistical significances (p<0.05) among these three subgroups. Comparing COP and MOP groups, the scores of OFS in the domains of "Speech-ability to speak in public" and "Swallowing-leakage with liquids" were significantly higher in AOP group. Comparing COP group, the scores of OFS in "Swallowing-leakage with solid" and "Chewing/eating" domains were increased significantly (p<0.05) both in MOP and AOP groups. CONCLUSION: Obturator prosthesis improves oral function of patients after maxillary defects; the retention of the obturator prosthesis enhanced by the addition of attachments showed more benefits in oral function. PMID- 26671023 TI - Assessing the Cumulative Contribution of New and Established Common Genetic Risk Factors to Early-Onset Prostate Cancer. AB - BACKGROUND: We assessed the evidence for association between 23 recently reported prostate cancer variants and early-onset prostate cancer and the aggregate value of 63 prostate cancer variants for predicting early-onset disease using 931 unrelated men diagnosed with prostate cancer prior to age 56 years and 1,126 male controls. METHODS: Logistic regression models were used to test the evidence for association between the 23 new variants and early-onset prostate cancer. Weighted and unweighted sums of total risk alleles across these 23 variants and 40 established variants were constructed. Weights were based on previously reported effect size estimates. Receiver operating characteristic curves and forest plots, using defined cut-points, were constructed to assess the predictive value of the burden of risk alleles on early-onset disease. RESULTS: Ten of the 23 new variants demonstrated evidence (P < 0.05) for association with early-onset prostate cancer, including four that were significant after multiple test correction. The aggregate burden of risk alleles across the 63 variants was predictive of early-onset prostate cancer (AUC = 0.71 using weighted sums), especially in men with a high burden of total risk alleles. CONCLUSIONS: A high burden of risk alleles is strongly associated with early-onset prostate cancer. IMPACT: Our results provide the first formal replication for several of these 23 new variants and demonstrate that a high burden of common-variant risk alleles is a major risk factor for early-onset prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(5); 766-72. (c)2015 AACR. PMID- 26671024 TI - Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review. AB - BACKGROUND: Accurately identifying latent tuberculosis (TB) infection (LTBI) in liver and renal transplant candidates is important because of the risks associated with both treatment of LTBI and reactivation of disease in this population. Many programs advocate yearly screening of patients awaiting organ transplantation. The reproducibility of serial interferon-gamma release assay (IGRA) testing in transplant candidates has not been studied. METHODS: We conducted a retrospective longitudinal study of patients listed for liver or kidney transplantation between January 1, 2005 and February 1, 2012 at the University of Illinois Medical Center at Chicago. Data collected included demographics, transplant type, IGRA results, treatment received, and mortality. RESULTS: The study population was comprised of 795 adults; 79 (10%) had at least 1 indeterminate result; indeterminate results were less common in men (P = 0.01) and more common in liver transplant candidates (P < 0.001). The reversion frequency was 27% with a rate of 158.1 reversions in 1000 person-years. A higher magnitude of initial TB response values was predictive of consistently positive results (P < 0.001). The conversion frequency was 15% with a rate of 82.6 conversions in 1000 person-years. Among those who converted, the values of the IGRA varied, with 48% having a TB response of <1 IU/mL, 41% 1-5 IU/mL, and only 10% >5 IU/mL. CONCLUSIONS: A significant number of conversions and reversions occur during serial IGRA testing of transplant candidates. Delineating true positive converters from false-positives is an issue that warrants further study. PMID- 26671025 TI - Functional Genetic Variants of PPARx03B3; and PPARalpha Encoding Peroxisome Proliferator-Activated Receptors and Susceptibility to Ischemic Stroke in Chinese Han Population. AB - BACKGROUND: PPARx03B3; and PPARalpha belong to a receptor family of ligand activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). METHODS: One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARx03B3; and PPARalpha genotypes and a diagnosis of IS. RESULTS: Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARalpha was extremely rare in Chinese Han population. CONCLUSIONS: PPARx03B3; 12Pro/Ala resulting in an amino acid exchange in N terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings. PMID- 26671026 TI - Melatonin attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism. AB - Myocardial dysfunction is an important manifestation of sepsis. Previous studies suggest that melatonin is protective against sepsis. In addition, activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been reported to be beneficial in sepsis. However, the role of PI3K/Akt signaling in the protective effect of melatonin against sepsis-induced myocardial dysfunction remains unclear. Here, LY294002, a PI3K inhibitor, was used to investigate the role of PI3K/Akt signaling in mediating the effects of melatonin on sepsis-induced myocardial injury. Cecal ligation and puncture (CLP) surgery was used to establish a rat model of sepsis. Melatonin was administrated to rats intraperitoneally (30 mg/kg). The survival rate, measures of myocardial injury and cardiac performance, serum lactate dehydrogenase level, inflammatory cytokine levels, oxidative stress level, and the extent of myocardial apoptosis were assessed. The results suggest that melatonin administration after CLP surgery improved survival rates and cardiac function, attenuated myocardial injury and apoptosis, and decreased the serum lactate dehydrogenase level. Melatonin decreased the production of the inflammatory cytokines TNF-alpha, IL-1beta, and HMGB1, increased anti-oxidant enzyme activity, and decreased the expression of markers of oxidative damage. Levels of phosphorylated Akt (p-Akt), unphosphorylated Akt (Akt), Bcl-2, and Bax were measured by Western blot. Melatonin increased p-Akt levels, which suggests Akt pathway activation. Melatonin induced higher Bcl-2 expression and lower Bax expression, suggesting inhibition of apoptosis. All protective effects of melatonin were abolished by LY294002, the PI3K inhibitor. In conclusion, our results demonstrate that melatonin mitigates myocardial injury in sepsis via PI3K/Akt signaling activation. PMID- 26671035 TI - Direct, Regioselective N-Alkylation of 1,3-Azoles. AB - Regioselective N-alkylation of 1,3-azoles is a valuable transformation. Organomagnesium reagents were discovered to be competent bases to affect regioselective alkylation of various 1,3-azoles. Counterintuitively, substitution selectively occurred at the more sterically hindered nitrogen atom. Numerous examples are provided, on varying 1,3-azole scaffolds, with yields ranging from 25 to 95%. PMID- 26671034 TI - An Epizootiological Report of the Re-emergence and Spread of a Lineage of Virulent Newcastle Disease Virus into Eastern Europe. AB - A number of contemporary outbreaks of Newcastle disease (ND) in Israel, Turkey, Georgia and Bulgaria have all been caused by a very similar viruses related to lineage 5a (genotype VIIa). Comparison with published ND virus (NDV) sequences suggests that this virus strain originated in South-East Asia and on introduction has circulated widely in backyard poultry in the Middle East and into Eastern Europe. An intracerebral pathogenicity index of 1.9 was obtained for a representative isolate from Bulgaria. In addition, the International Reference Laboratory for ND has characterized a molecular epidemiologically linked virus that has been reported to have caused disease in well-vaccinated broiler chickens in Pakistan. In the 1990s, another strain from the 5a lineage NDV was introduced into Europe and spread across the continent causing numerous outbreaks up to 1999. Despite improved controls, including good diagnostic tests and widespread vaccination, in commercial poultry, the novel circulating NDV strains described here have been established widely in the region and represent an increased risk for similar disease outbreak events to reoccur within the EU. PMID- 26671036 TI - Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer. AB - BACKGROUND: Methylation changes within tumor suppressor (TS) genes or polycomb group target (PcG) genes alter cell fates. Chromatin associated with PcG targets is bivalent in stem cells, while TS genes are not normally bivalent. PcG target methylation changes have been identified in tumor stem cells, and abnormal methylation is found in TS genes in cancers. If the epigenetic states of genes influence DNA methylation, then methylation of PcG targets and TS genes may evolve differently during cancer development. More importantly, methylation changes may be part of a sequence in tumorigenesis. METHODS: Chromatin and methylation states of 4 PcG targets and 2 TS genes were determined in colon cancer cells. The methylation states were also detected in 100 pairs of colon cancer samples. Principle component analysis (PCA) was used to reveal whether TS methylation or PcG methylation was the main methylation change associated with colon cancers. RESULTS: Chromatin and methylation states differ in colon cancer cell lines. The methylation states within PcG targets clustered independently from the methylation states in TS genes, a finding we previously reported in liver cancers. PCA in colon cancers revealed the strongest association with methylation changes in 2 TS genes, HIC1 and RassF1A. Loss of HIC1 methylation correlated with decreased tumor migration. CONCLUSIONS: PcG and TS methylation states cluster independently from each other. The deduced principle component correlated better with TS methylation than PcG methylation in colon cancer. Abnormal methylation changes may represent a sequential biomarker profile to identify developing colon cancer. PMID- 26671037 TI - Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor Recurrence in Non-muscle Invasive Bladder Cancer Patients. AB - PURPOSE: We investigated whether smoking cessation could have preventative effects against tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Our study population comprised 634 patients with initially diagnosed NMIBC at Keio University Hospital, Saiseikai Central Hospital, and Saitama Medical University Hospital between 1995 and 2012. We analyzed the relationships between tumor recurrence in NMIBC and patient clinicopathological parameters, including smoking status. RESULTS: Overall, 181 patients (28.5 %) were classified as current smokers, 154 (24.3 %) as former smokers, and 299 (47.2 %) as non-smokers. Kaplan-Meier curve analysis revealed that the tumor recurrence rate was significantly lower in the non-smoker group than in the current- and former-smoker groups (p < 0.001 and p < 0.001, respectively). In the 154 former smokers, Kaplan-Meier curve analysis revealed that smoking intensity and duration was not associated with tumor recurrence rate; however, patients with a smoking cessation period of 15 years or more had a significantly lower tumor recurrence rate than their counterparts (p < 0.001). A multivariate analysis identified a smoking cessation period of <15 years (hazard ratio [HR] 2.20; p = 0.003) and T1 tumors (HR 1.99; p = 0.013) as independent risk factors for tumor recurrence in the former-smokers subgroup. CONCLUSIONS: A positive smoking history was identified as one of the independent risk factors for bladder tumor recurrence after transurethral resection of the bladder tumor. Furthermore, refraining from smoking for 15 years or more reduced the risk of tumor recurrence in former smokers with NMIBC regardless of the intensity or duration of smoking. Therefore, smoking cessation may reduce the risk of tumor recurrence in patients with NMIBC. PMID- 26671038 TI - Selection of Lymph Node-Positive Cases Based on Perirectal and Lateral Pelvic Lymph Nodes Using Magnetic Resonance Imaging: Study of the Japanese Society for Cancer of the Colon and Rectum. AB - PURPOSE: To investigate the optimum cutoff for lymph node size to identify cases positive for perirectal lymph node (PRLN) and lateral lymph node (LPLN) metastasis of lower rectal cancer on magnetic resonance imaging (MRI). METHODS: The subjects were 449 patients who underwent preoperative MRI. Mesorectal excision was performed in all patients (combined with lateral pelvic lymph node [LN] dissection in 324) between 2004 and 2013 at 6 institutes. Cases were classified as cN positive and cN negative on the basis of the short axis of the largest LN being greater than or equal to a cutoff or less than a cutoff, respectively. PRLN and LPLN diagnoses using 5 and 10 mm cutoffs were compared with histologic diagnoses. Of the 449 patients, 55 received preoperative chemoradiotherapy. MRI was only performed after this therapy in all of these patients. RESULTS: For PRLNs, 5 and 10 mm cutoffs gave area under the curve (AUC) values of 0.6364 and 0.5794, respectively. The 5 mm cutoff gave a significantly higher AUC value (P = 0.0152), with an accuracy of 63.7 %, sensitivity of 72.6 %, and specificity of 54.7 %. For right LPLNs, the respective AUC values were 0.7418 and 0.6326 (P = 0.0034), and the variables (5 mm cutoff) were 77.6, 68.6, and 79.7 %. For left LPLNs, AUC values were 0.7593 and 0.6559, respectively (P = 0.0057), and the variables (5 mm cutoff) were 79.3, 70.8, and 81.0 %. CONCLUSIONS: Identification of LN-positive cases on the basis of PRLN and LPLN sizes was superior at a short-axis 5 mm cutoff. Size-based diagnosis of LN metastasis is simple and useful, but further investigation is needed to clarify whether it is superior to diagnosis based on morphology, such as shape, border, and signal intensity. PMID- 26671039 TI - Mechanisms governing phonon scattering by topological defects in graphene nanoribbons. AB - Understanding phonon scattering by topological defects in graphene is of particular interest for thermal management in graphene-based devices. We present a study that quantifies the roles of the different mechanisms governing defect phonon scattering by comparing the effects of ten different defect structures using molecular dynamics. Our results show that phonon scattering is mainly influenced by mass density difference, with general trends governed by the defect formation energy and typical softening behaviors in the phonon density of state. The phonon scattering cross-section is found to be far larger than that geometrically occupied by the defects. We also show that the lattice thermal conductivity can be reduced by a factor of up to ~30 in the presence of the grain boundaries formed by these defects. PMID- 26671040 TI - Periosteal Fiber Transection During Periosteal Procedures Is Crucial to Accelerate Growth in the Rabbit Model. AB - BACKGROUND: Disruption of the periosteum has been used to explain overgrowth after long bone fractures. Clinically, various periosteal procedures have been reported to accelerate growth with varied results. Differences between procedures and study populations, in these prior studies, make drawing conclusions regarding their effectiveness difficult. QUESTIONS/PURPOSES: The purpose of this study was to (1) determine if all reported periosteal procedures accelerate growth and increase the length of bones; (2) study the relative duration of these growth accelerating effects at two time points; and (3) identify the periosteal procedure that results in the most growth. METHODS: Periosteal stripping (N = 8), periosteal transection (N = 8), periosteal resection (N = 8), (and) full periosteal release (N = 8) were performed on the tibiae of skeletally immature rabbits. Tibiae were collected 2 weeks postoperatively. The tibiae of additional cohorts of periosteal transection (N = 8), periosteal resection (N = 8), full periosteal release (N = 8), and repetitive periosteal transection (N = 8) were collected 8 weeks postoperatively. The contralateral tibiae served as an operative sham control in all cohorts. Fluorochrome bone labeling was used to measure growth rates, whereas high-resolution Faxitron imaging was performed to measure tibial lengths. Comparisons were then made between (1) experimental and sham controls; and (2) different procedures. Eight additional nonsurgical animals were included as age-matched controls. RESULTS: Growth (in microns) was accelerated at the proximal tibial physis on the tibia undergoing the periosteal surgical procedures versus the contralateral control limb after the transection (411 +/- 27 versus 347 +/- 18, p < 0.001 [mean +/- SD]), resection (401 +/- 33 versus 337 +/- 31, p < 0.001), and full periosteal release (362 +/- 45 versus 307 +/- 33, p < 0.001), 2 weeks after the index procedure. Conversely, the periosteal stripping cohort trended toward less growth (344 +/- 35) than the controls (356 +/- 25; p = 0.08). No differences were found between limbs in the nonoperative controls. Tibial lengths for the experimental tibiae were longer at 2 weeks in the transection (1.6 +/- 0.4 mm, p < 0.001), resection (1.6 +/- 0.9 mm, p = 0.03), and full periosteal release (1.7 +/- 0.5 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (0.13 +/- 0.7 mm, p = 0.8) and stripping cohorts (0.10 +/- 0.6 mm, p = 0.7). At 8 weeks, growth acceleration ceased at the proximal tibial physes in the transection cohort (174 +/- 11 versus 176 +/- 21, p = 0.8), and the control limbs actually grew faster than the experimental limbs after resection (194 +/- 24 versus 178 +/- 23, p = 0.02) and full periosteal release (193 +/- 16 versus 175 +/- 19, p < 0.01) cohorts. Growth rates were increased over control limbs, only in the repetitive transection cohort (190 +/- 30 versus 169 +/- 19, p = 0.01) at 8 weeks. Tibial lengths for the experimental tibiae remained longer at 8 weeks in the transection (1.4 +/- 0.70 mm, p < 0.001), resection (2.2 +/- 0.82 mm, p < 0.001), full periosteal release (1.6 +/- 0.42 mm, p < 0.001), and repetitive periosteal transection (3.3 +/- 1.1 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (-0.08 +/- 0.58 mm, p = 0.8). Comparing the procedures at 2 weeks postoperatively, no differences were found in tibial lengths among the transection (2.1% +/- 0.5% increase), resection (2.1% +/- 1.1% increase), and full periosteal release (2.1% +/- 0.6 %); however, all three demonstrated greater increased growth when compared with the stripping cohort (-0.10% +/- 0.7%; p < 0.05). At 8 weeks no differences could be found between increased tibial lengths among the transection (1.5% +/- 0.7%), resection (2.3% +/- 0.9%), and full periosteal release (1.7% +/- 0.4%). The repetitive transection produced the greatest over length increase (3.5% +/- 1%), and this was greater than the acceleration generated by the single resection (p < 0.001) or the full periosteal release (p = 0.001). All four demonstrated an increase greater than the nonoperative control (0.09% +/- 0.6%; p < 0.05). CONCLUSIONS: Transection of the longitudinally oriented periosteal fibers appears critical to accelerate growth in a rabbit model. CLINICAL RELEVANCE: These findings in an animal model support previous claims that limb overgrowth occurs as the result of periosteal disruption. Based on these findings in rabbits, we believe that less invasive procedures like periosteal transection are a promising avenue to explore in humans; clinical studies should seek to determine whether it is equally effective as more invasive procedures and its role as an adjunct to guided growth or distraction osteogenesis. PMID- 26671042 TI - Semiconductor and carbon-based fluorescent nanodots: the need for consistency. AB - Fluorescent nanodots have become increasingly prevalent in a wide variety of applications with special interest in analytical and biomedical fields. The present overview focuses on three main aspects: (i) a systematic description and reasonable classification of the most relevant types of fluorescent nanodots according to their nature, quantum confinement and crystalline structure is provided, starting with a clear distinction between semiconductor and carbon based dots (graphene quantum dots, carbon quantum dots and carbon nanodots). A new set of abbreviations and definitions for them to avoid contradictions found in literature is also proposed; (ii) a rational classification allows the establishment of clear-cut differences and similarities among them. From a basic point of view, the origins of the photoluminescence of the different nanodots are also established, which is a relevant contribution of this overview. Additionally, the most outstanding similarities and differences in a great variety of criteria (i.e. year of discovery, synthesis, the physico-chemical characteristics like structure, nature, shape, size, quantum confinement, toxicity and solubility, the optical characteristics including the quantum yield and lifetime, limitations, applications as well as the evolution of publications) are thoroughly outlined; and (iii) finally, the promising future of fluorescent nanodots in both analytical and biomedical fields is discussed using selected examples of relevant applications. PMID- 26671041 TI - Reply to the Letter to the Editor: Low Albumin Levels, More Than Morbid Obesity, Are Associated With Complications After TKA. PMID- 26671043 TI - Role of 18-Fludeoxyglucose positron emission tomography-computed tomography and subsequent panendoscopy in head and neck squamous cell carcinoma of unknown primary. AB - OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinomas of unknown primary (HNSCCUP) accounts for up to 10% of presenting head and neck squamous cell carcinomas. Identification of the primary site allows for directed therapy. Where initial investigations have failed to locate the primary site, 18-fludeoxyglucose positron emission tomography-computed tomography (PET/CT) has emerged as a useful tool with improved sensitivity over positron emission tomography alone. Following PET/CT scan, the role of subsequent panendoscopy +/- biopsy has not been fully assessed. We aim to evaluate and quantify the role of PET/CT and subsequent panendoscopy in HNSCCUP. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with HNSCCUP presenting between January 2005 and December 2010 at a regional oncology referral center were studied. All patients who presented with a metastatic neck node and unknown primary who had undergone PET/CT prior to panendoscopy were included. The accuracy of PET/CT was calculated and compared with panendoscopy and histopathological findings. RESULTS: Fifty-two patients were included. Twenty-seven PET/CT scans suggested a primary site. Calculated diagnostic parameters were 83% sensitivity, 87% specificity, positive predictive value 89%, and negative predictive value 80%. Three false-positive PET/CT scans were noted after panendoscopy and normal histology. Importantly, three confirmed tongue base tumors were found on panendoscopy, which were undetected on PET/CT. CONCLUSIONS: PET/CT is a valuable resource for locating tumors in HNSCCUP. It helps direct biopsy and aids in the detection of local and distant metastases along with synchronous primary tumors. Importantly, due to both false-positive and false-negative PET/CT rates, panendoscopy and biopsy remains an essential adjunct investigation irrespective of PET/CT results. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1354-1358, 2016. PMID- 26671044 TI - All-photonic intercity quantum key distribution. AB - Recent field demonstrations of quantum key distribution (QKD) networks hold promise for unconditionally secure communication. However, owing to loss in optical fibres, the length of point-to-point links is limited to a hundred kilometers, restricting the QKD networks to intracity. A natural way to expand the QKD network in a secure manner is to connect it to another one in a different city with quantum repeaters. But, this solution is overengineered unless such a backbone connection is intercontinental. Here we present a QKD protocol that could supersede even quantum repeaters for connecting QKD networks in different cities below 800 km distant. Nonetheless, in contrast to quantum repeaters, this protocol uses only a single intermediate node with optical devices, requiring neither quantum memories nor quantum error correction. Our all-photonic 'intercity' QKD protocol bridges large gaps between the conventional intracity QKD networks and the future intercontinental quantum repeaters, conceptually and technologically. PMID- 26671046 TI - Magnetic and Photochromic Properties of a Manganese(II) Metal-Zwitterionic Coordination Polymer. AB - The solvothermal reaction of Mn(ClO4)2, NaN3, and a rigid viologen-tethered tetracarboxylic acid (1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium chloride, [H4L]Cl2) led to a coordination polymer of formula [Mn4(L)(N3)6(H2O)2]n. X-ray analysis revealed a 3D coordination structure. The Mn(II) ions are connected by mixed azide and carboxylate bridges to give 2D layers, which are pillared by the viologen tether of the zwitterionic ligand. Magnetic analyses suggested that the compound features antiferromagnetism and field-induced metamagnetism. The compound also shows photochromic and photomagnetic properties. The long-range magnetic ordering is owed to the spin-canting structure of the Mn(II)-azide carboxylate layer; the photochromism involves the formation of viologen radicals via photoinduced electron transfer, and the photomagnetism is related to the interactions between the metal ion and the photogenerated radicals. The study demonstrates a strategy for the design of new multifunctional materials with photoresponsive properties. PMID- 26671047 TI - Editorial. PMID- 26671045 TI - Tumor/normal esophagus ratio in (18)F-fluorodeoxyglucose positron emission tomography/computed tomography for response and prognosis stratification after neoadjuvant chemotherapy for esophageal squamous cell carcinoma. AB - BACKGROUND: Positron emission tomography (PET) response criteria in solid tumors were recently proposed as a standardized method for the metabolic and quantitative assessment of response to chemotherapy. However, use of these criteria is limited in many institutions because of the need for exclusive software. This study was designed to clarify whether tumor to normal esophageal (T/N) ratio on (18)F-fluorodeoxyglucose PET/computed tomography could predict response to neoadjuvant chemotherapy and stratify prognosis in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Clinicopathological data were collected for 73 patients with ESCC who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by curative resection. The right liver lobe and normal esophagus were utilized as reference tissues for diagnosing complete metabolic response (CMR). Statistical methods included Kaplan Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS: CMR was achieved in 24 patients on the basis of maximum standardized uptake value (SUVmax) and in 11 on the basis of SUVmax evaluation with T/N ratio. Although prognosis was poorer in patients who achieved CMR than partial metabolic response based on SUVmax, the responses were significantly correlated with disease-free survival (DFS) based on SUVmax evaluation with T/N ratio (P = 0.0011). Receiver operating characteristic curve analysis showed that SUVmax evaluation with T/N ratio was the best predictor of pGrade 3. Multivariate analysis showed that SUVmax evaluation with T/N ratio was an independent predictor of DFS in patients with pGrade 1 pathologic response. CONCLUSIONS: SUVmax evaluation with T/N ratio is useful for evaluating the effects of neoadjuvant chemotherapy in patients with ESCC. PMID- 26671048 TI - Resolving the Magnetic Asymmetry of the Inner Space in Self-assembled Dimeric Capsules Based on Tetraurea-calix[4]pyrrole Components. AB - The encapsulation of N,N, N',N'-tetramethyl-1,5-pentanediamine-N,N'-dioxide 2 in a non-chiral capsular assembly formed by dimerization of tetraurea calix[4]pyrrole 1a produced the observation of the N-methyl groups of the encapsulated guest as two separated singlets resonating highly upfield in the (1)H NMR spectrum. In order to clarify the origin of the observed signal splitting we assembled and studied a series of structurally related dimeric capsules. We used the tetraurea-calix[4]pyrrole 1a , the enantiomerically pure tetraurea-calix[4] pyrrole R-1b and the tetraurea-bisloop calix[4]pyrrole 1c as components of the produced assemblies. The (1)H NMR spectra of the assembled encapsulation complexes with bis-N-oxide 2 evidenced diverse splitting patterns of the N-methyl groups. In addition, 2D EXSY/ROESY NMR experiments revealed the existence of chemical exchange processes involving the separated methyl signals of the encapsulated guest. The capsular assemblies were mainly stabilized by a belt of eight head-to-tail hydrogen-bonded urea groups. The interconversion between the two senses of rotation of the unidirectionally oriented urea groups was slow on the (1)H NMR timescale. These characteristics determined the appearance of a new asymmetry element (supramolecular conformational chirality) in the assemblies that accounted for some of the magnetic asymmetries featured by the capsule's inner space. The racemization of the supramolecular chirality element was fast on the EXSY timescale and produced the chemical exchange processes detected for the encapsulation complexes. PMID- 26671049 TI - Transition Metal Complexes of Bidentate and Tridentate Ligands: From Optoelectronic Studies to Supramolecular Assemblies. AB - This article depicts an overview of some of the research in supramolecular chemistry performed by the author over the past few years. This work includes the synthesis of building blocks, bidentate and tridentate 'super donor' ligands that are comprised of H-hpp (where H-hpp = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a] pyrimidine) coupled with various N-heterocycles as well as the synthesis and characterization of the transition metal complexes in self-assembled superstructures. The article also includes the studies of photophysical, electrochemical and density functional theory calculation of the complexes. Thus, the work relies on a combination of synthetic work and optoelectronic studies, and the results are relevant in the greater context of supramolecular chemistry, solar energy harvesting, and its conversion to chemical energy, photovoltaics and inorganic light-emitting device applications. PMID- 26671050 TI - Two-photon Absorption Engineering of 5-(Fluorenyl)-1,10-phenanthroline-based Ru(II) Complexes. AB - This study deals with the fine tuning of the photophysical characteristics, and especially two-photon absorption (2PA) properties, of several homo- and heteroleptic ruthenium(II) complexes involving 5-substituted-1,10-phenanthroline ligands. The 2PA spectra of the complexes were determined in the 700-930 nm range by investigating their two-photon excited luminescence (2PEL). Structure - linear and nonlinear optical properties correlations are discussed, and potential applications (therapy and optical power limiting in the near infrared) can be anticipated. PMID- 26671051 TI - Dimension Increase via Hierarchical Hydrogen Bonding from Simple Pincer-like Mononuclear complexes. AB - A tetradentate symmetric ligand bearing both coordination and hydrogen bonding sites, N(1),N(3)-bis(1-(1H-benzimidazol-2-yl)-ethylidene)propane-1,3-diamine (H2bbepd) was utilized to synthesize a series of transition metal complexes, namely [Co(H2bbepd)(H(2)O)2].2ClO(4) (1), [Cu(H2bbepd)(OTs(-))].OTs(-) (2),[Cu(bbepd)(CH(3)OH)] (3), [Cd(H(2)bbepd)(NO3)2].CH(3)OH (4), [Cd(H(2)bbepd)(CH(3)OH)Cl].Cl (5), and [Cd(bbepd)(CH(3)OH)2] (6). These complexes show similar discrete pincer-like coordination units, possessing different arrangements of hydrogen bonding donor and acceptor sites. With or without the aid of uncoordinated anions and solvent molecules, such mononuclear units have been effectively involved in the construction of hierarchical hydrogen bonding assemblies (successively via level I and level II), leading to discrete binuclear ring (complex 2), one-dimensional chain or ribbon (complexes 3, 4 and 6) and two dimensional layer (complexes 1 and 5) aggregates. PMID- 26671052 TI - Rhenium(I)-based Double-heterostranded Helicates. AB - Rhenium(I)-based supramolecular coordination complexes were obtained using Re2(CO)10, (2-hydroxyphenyl)benzimidazole-derived bis-chelating N?O donors and a benzimidazolyl-derived ditopic monodentate N-donor possessing Troger's base spacer in a one-pot approach. PMID- 26671053 TI - Porphyrin-modified DNA as Construction Material in Supramolecular Chemistry and Nano-architectonics. AB - An overview is given on the developments of using porphyrin-modified DNA for the construction of functional assemblies. Strategies for the synthesis and characterisation are presented alongside selected applications where the porphyrin modification has proven to be particularly useful, but also revealed its limitations. We also discuss implications on property and behaviour of the porphyrin-DNA, where similar issues could arise using other hydrophobic and bulky substituents on DNA. PMID- 26671054 TI - Development of an LC-MS/MS Method for the Assessment of Selected Active Pharmaceuticals and Metabolites in Wastewaters of a Swiss University Hospital. AB - A multi-residue analytical method was developed and validated for the quantification of 11 selected active pharmaceutical ingredients (API) and 2 human metabolites in hospital effluents using solid-phase extraction followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Targeted analytes belong to different therapeutic classes: non steroidal anti-inflammatory drugs (NSAID), analgesics, antibiotics and psychiatric drugs. Solid-phase extraction recoveries ranged between 21 and 101% for the selected API. Calibration curves were built with 6 standard samples prepared in ultrapure water ranging from 0.05 to 10 MUg/L and showed regression coefficients above 0.994. The instrumental detection limits (IDL) varied between 0.05 and 5 MUg/L, and the method detection limits (MDL) between 0.1 and 100 ng/L. Precision of the method, evaluated with spiked water samples at four different concentrations, varied between 84 and 117% for all compounds and an overall variability below 20%, with the exception of carbamazepine (71-123%). Except for two compounds, recoveries of spiked hospital wastewaters at four different concentrations (0.1, 1, 10 and 100 MUg/L) varied between 44 and 133%, with relative standard deviation (RSD) between 0.6 and 28.5%. The evaluation of the matrix effects showed that diluted samples exhibit lower signal suppression. Analysis of effluent samples from a Swiss university hospital resulted in a mean detection frequency of 92% for the selected compounds, with concentrations up to 1535 MUg/L for the analgesic paracetamol. PMID- 26671055 TI - A Network Sets Things in Motion: TEDD Celebrates its 5(th) Anniversary. AB - At the Annual Meeting at ZHAW Waedenswil on 22 October 2015, the TEDD-Network (Tissue Engineering for Drug Development and Substance Testing) celebrated its 5(th) anniversary. Since its foundation, TEDD has become an internationally renowned competence centre and includes currently 91 members from academia and industry. They cover the entire development and value chain. PMID- 26671056 TI - 12. Freiburger Symposium 2015: Smart Solutions in the Chemical Process & Product Development - Case Studies from the Chemical Industry. PMID- 26671057 TI - Multi-Component Trace Gas Spectroscopy Using Dual-Wavelength Quantum Cascade Lasers. PMID- 26671058 TI - Lateral Deformability of Polymer Brushes by AFM-Based Method. PMID- 26671059 TI - Moving 3D Cell CUltures from Bench to Practice: TEDD Annual Meeting at ZHAW Waedenswil 22 Octorber 2015. AB - Three-dimensional (3D) cell culture technology captures the market! Driving forces include an increase in cancer worldwide, but also reinforced research for biopharmaceutical products to cure diseases and to reduce animal experiments. The challenge now is to translate in vitro assays into relevant in vivo outcomes. At the TEDD Annual Meeting, selected experts explored this problem and discussed how to move 3D cell cultures from bench to practice. PMID- 26671060 TI - Lung anatomy, energy load, and ventilator-induced lung injury. AB - BACKGROUND: High tidal volume can cause ventilator-induced lung injury (VILI), but positive end-expiratory pressure (PEEP) is thought to be protective. We aimed to find the volumetric VILI threshold and see whether PEEP is protective per se or indirectly. METHODS: In 76 pigs (22 +/- 2 kg), we examined the lower and upper limits (30.9-59.7 mL/kg) of inspiratory capacity by computed tomography (CT) scan at 45 cmH2O pressure. The pigs underwent a 54-h mechanical ventilation with a global strain ((tidal volume (dynamic) + PEEP volume (static))/functional residual capacity) from 0.45 to 5.56. The dynamic strain ranged from 18 to 100 % of global strain. Twenty-nine pigs were ventilated with end-inspiratory volumes below the lower limit of inspiratory capacity (group "Below"), 38 within (group "Within"), and 9 above (group "Above"). VILI was defined as death and/or increased lung weight. RESULTS: "Below" pigs did not develop VILI; "Within" pigs developed lung edema, and 52 % died before the end of the experiment. The amount of edema was significantly related to dynamic strain (edema 188-153 * dynamic strain, R (2) = 0.48, p < 0.0001). In the "Above" group, 66 % of the pigs rapidly died but lung weight did not increase significantly. In pigs ventilated with similar tidal volume adding PEEP significantly increased mortality. CONCLUSIONS: The threshold for VILI is the lower limit of inspiratory capacity. Below this threshold, VILI does not occur. Within these limits, severe/lethal VILI occurs depending on the dynamic component. Above inspiratory capacity stress at rupture may occur. In healthy lungs, PEEP is protective only if associated with a reduced tidal volume; otherwise, it has no effect or is harmful. PMID- 26671061 TI - Performance Evaluation and Implementation of FPGA Based SGSF in Smart Diagnostic Applications. AB - The main objective of the paper is to implement Savitzky Golay Smoothing Filter (SGSF) so as to apply in pre-processing of real time smart medical diagnostic systems. As very important information of EEG and ECG waveforms lies in the peak of the signal, hence it becomes absolutely necessary to filter noise and artifacts from the signal. The implemented filter should be able to reject the noise efficiently along with the least distortion from the original signal. The shape preserving characteristics of the filter are determined by introducing different noise levels in the signal. The designed filter is tested on synthetic signals of EEG and ECG by adding different types of noise and the performance is analysed on various parameters, i.e., SNR, SSNR, SNRI, MSE, COR and signal distortion of the final output. The smoothing performance comparison of SGSF with the most commonly used Moving Average Filter (MAF) proves that SGSF is more efficient. Hence it is suggested that MAF can be replaced by SGSF. For real time issues, it is further implemented on reconfigurable architectures so as to achieve high speed, low cost, low power consumption and less area. Therefore SGSF is realized on FPGA platform to combine the advantages of both. Real time EEG and ECG signals are also considered for experimentation. The experimental results show that the proposed methodology (FPGA-SGSF) significantly reduces the processing time and preserves the actual features of the signal. PMID- 26671062 TI - Home versus hospital intravenous antibiotic therapy for cystic fibrosis. AB - BACKGROUND: Recurrent endobronchial infection in cystic fibrosis requires treatment with intravenous antibiotics for several weeks usually in hospital, affecting health costs and quality of life for patients and their families. This is an update of a previously published review. OBJECTIVES: To determine whether home intravenous antibiotic therapy in cystic fibrosis is as effective as inpatient intravenous antibiotic therapy and if it is preferred by individuals or families or both. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search of the Group's Trials Register: 23 November 2015. SELECTION CRITERIA: Randomized and quasi randomized controlled studies of intravenous antibiotic treatment for adults and children with cystic fibrosis at home compared to in hospital. DATA COLLECTION AND ANALYSIS: The authors independently selected studies for inclusion in the review, assessed methodological quality of each study and extracted data using a standardised form. MAIN RESULTS: Eighteen studies were identified by the searches. Only one study could be included which reported results from 17 participants aged 10 to 41 years with an infective exacerbation of Pseudomonas aeruginosa. All their 31 admissions (18 hospital and 13 at home after two to four days of hospital treatment) were analysed as independent events. Outcomes were measured at 0, 10 and 21 days after initiation of treatment. Home participants underwent fewer investigations than hospital participants (P < 0.002) and general activity was higher in the home group. No significant differences were found for clinical outcomes, adverse events, complications or change of intravenous lines,or time to next admission. Home participants received less low-dose home maintenance antibiotic.Quality of life measures showed no significant differences for dyspnoea and emotional state, but fatigue and mastery were worse for home participants, possibly due to a higher general activity and need of support. Personal, family, sleeping and eating disruptions were less important for home than hospital admissions.Home therapy was cheaper for families and the hospital. Indirect costs were not determined. AUTHORS' CONCLUSIONS: Current evidence is restricted to a single randomized clinical trial. It suggests that, in the short term, home therapy does not harm individuals, entails fewer investigations, reduces social disruptions and can be cost-effective. There were both advantages and disadvantages in terms of quality of life. The decision to attempt home treatment should be based on the individual situation and appropriate local resources. More research is urgently required. PMID- 26671063 TI - Ex vivo motility in the base of the rabbit caecum and its associated structures: an electrophysiological and spatiotemporal analysis. AB - We examined the coordination between contractile events at different sites in the basal portion of the rabbit caecum and its associated structures that were identified by electrophysiological recordings with simultaneous one-dimensional, and a novel two-dimensional, spatiotemporal mapping technique. The findings of this work provide evidence that the caecum and proximal colon/ampulla coli act reflexly to augment colonic outflow when the caecum is distended and mass peristalsis instituted, the action of the latter overriding the inherent rhythm and direction of haustral propagation in the adjacent portion of the proximal colon but not in the terminal ileum. Further, the findings suggest that the action of the sacculus rotundus may result from its distension with chyme by ileal peristalsis and that the subsequent propagation of contraction along the basal wall of the caecum towards the colon may be augmented by this local distension. PMID- 26671064 TI - Cerasomes: Soft Interface for Redox Enzyme Electrochemical Signal Transmission. AB - Anionic cerasomes, which consist of a liposomal lipid bilayer and a ceramic surface, were used as a soft interface for the construction of an integrated modified electrode to achieve the transmission of chemical information from a redox enzyme through electrical signals. The morphological properties of the cerasomes were systematically compared with those of two structural analogues, namely, liposomes and silica nanoparticles. The results indicated that the cerasomes combined the advantages of liposomes and silica nanoparticles. The lipid bilayer gave excellent biocompatibility, as in the case of liposomes, and high structural stability, similar to that of silica nanoparticles, was derived from the silicate framework on the cerasome surface. The performance at the electrochemical interface created by means of a combination of cerasomes and horseradish peroxidase on a glassy carbon electrode was much better than those achieved with liposomes or silica nanoparticles instead of cerasomes. The potential use of cerasomes in the construction of supramolecular devices for mediator-free biosensing was evaluated. PMID- 26671065 TI - The Reaction of DABCO with 4-Chloro-5H-1,2,3-dithiazoles: Synthesis and Chemistry of 4-[N-(2-Chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazoles. AB - N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70-92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol 5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5 ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl] 5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition-retrocycloaddition strategies from 4-[N-(2 chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3 dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2 substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields. PMID- 26671066 TI - Special Issue: Proceedings of the 8th International Conference on Nemertean Biology. PMID- 26671067 TI - Short-term effects of a pay-for-performance programme for diabetes in a primary care setting: an observational study. AB - OBJECTIVE: A pay-for-performance (P4P) programme for primary care was introduced in 2011 by a Swedish county (with 1.6 million inhabitants). Effects on register entry practice and comparability of data for patients with diabetes mellitus were assessed. DESIGN AND SETTING: Observational study analysing short-term outcomes before and after introduction of a P4P programme in the study county as compared with a reference county. SUBJECTS: A total of 84 053 patients reported to the National Diabetes Register by 349 primary care units. MAIN OUTCOME MEASURES: Completeness of data, level and target achievement of glycated haemoglobin (HbA1c), blood pressure (BP), and LDL cholesterol (LDL). RESULTS: In the study county, newly recruited patients who were entered during the incentive programme were less well controlled than existing patients in the register - they had higher HbA1c (54.9 [54.5-55.4] vs. 53.7 [53.6-53.9] mmol/mol), BP, and LDL. The percentage of patients with entry of BP, HbA1c, LDL, albuminuria, and smoking increased in the study county but not in the reference county (+26.3% vs -1.5%). In the study county, with an incentive for BP < 130/80 mmHg, BP data entry behaviour was altered with an increased preference for sub-target BP values and a decline in zero end-digit readings (38.3% vs. 33.7%, p < 0.001). CONCLUSION: P4P led to increased register entry, increased completeness of data, and altered BP entry behaviour. Analysis of newly added patients and data shows that missing patients and data can cause performance to be overestimated. Potential effects on reporting quality should be considered when designing payment programmes. Key points A pay-for-performance programme, with a focus on data entry, was introduced in a primary care region in Sweden. Register data entry in the National Diabetes Register increased and registration behaviour was altered, especially for blood pressure. Newly entered patients and data during the incentive programme were less well controlled. Missing data in a quality register can cause performance to be overestimated. PMID- 26671068 TI - SLC26A Gene Family Participate in pH Regulation during Enamel Maturation. AB - The bicarbonate transport activities of Slc26a1, Slc26a6 and Slc26a7 are essential to physiological processes in multiple organs. Although mutations of Slc26a1, Slc26a6 and Slc26a7 have not been linked to any human diseases, disruption of Slc26a1, Slc26a6 or Slc26a7 expression in animals causes severe dysregulation of acid-base balance and disorder of anion homeostasis. Amelogenesis, especially the enamel formation during maturation stage, requires complex pH regulation mechanisms based on ion transport. The disruption of stage specific ion transporters frequently results in enamel pathosis in animals. Here we present evidence that Slc26a1, Slc26a6 and Slc26a7 are highly expressed in rodent incisor ameloblasts during maturation-stage tooth development. In maturation-stage ameloblasts, Slc26a1, Slc26a6 and Slc26a7 show a similar cellular distribution as the cystic fibrosis transmembrane conductance regulator (Cftr) to the apical region of cytoplasmic membrane, and the distribution of Slc26a7 is also seen in the cytoplasmic/subapical region, presumably on the lysosomal membrane. We have also examined Slc26a1 and Slc26a7 null mice, and although no overt abnormal enamel phenotypes were observed in Slc26a1-/- or Slc26a7-/- animals, absence of Slc26a1 or Slc26a7 results in up-regulation of Cftr, Ca2, Slc4a4, Slc4a9 and Slc26a9, all of which are involved in pH homeostasis, indicating that this might be a compensatory mechanism used by ameloblasts cells in the absence of Slc26 genes. Together, our data show that Slc26a1, Slc26a6 and Slc26a7 are novel participants in the extracellular transport of bicarbonate during enamel maturation, and that their functional roles may be achieved by forming interaction units with Cftr. PMID- 26671070 TI - Melanosis in Penaeus monodon: Involvement of the Laccase-like Activity of Hemocyanin. AB - In shrimp, the development of postmortem melanosis resulting from phenoloxidase activities leads to important economic losses. Phenoloxidase enzymes include catechol oxidases, laccases, and tyrosinases, but hemocyanin is also capable of phenoloxidase activities. These activities have been explored in Penaeus monodon, using different substrates. Results highlighted that tyrosinase-specific substrates were little oxidized, whereas hydroquinone (laccase-specific substrate) was more highly oxidized than l-DOPA (nonspecific substrate) in the pereopods and pleopods. Global phenoloxidase activity, assayed with l-DOPA, did not appear thermally stable over time and probably resulted from phenoloxidase enzymes. Conversely, the laccase-like activity assayed with hydroquinone was thermally stable over time, reflecting the thermal stability of hemocyanin. Independently of the anatomical compartment, the temperature, or the substrate, the highest activities were assayed in the cuticular compartments. This study demonstrates the complexity of phenoloxidase activities in P. monodon, and the importance of considering all the activities, including laccase-like activities such as that of hemocyanin. PMID- 26671069 TI - Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle. AB - Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of alpha ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle- regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/ mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD. PMID- 26671071 TI - Comparison of Time Trends of Cardiovascular Disease Risk Factors and Framingham Risk Score Between Patients With and Without Acute Coronary Syndrome Undergoing Percutaneous Intervention Over the Last 17 Years: From the Mayo Clinic Percutaneous Coronary Intervention Registry. AB - BACKGROUND: The objective of this study was to investigate cardiovascular disease risk factor (cvRF) profiles and compare their trends over 17 years in patients with and without acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). HYPOTHESIS: Time trends of cvRF are different between ACS and non-ACS patients. METHODS: This study was a time-trend analysis from 1994 to 2010 within the Mayo Clinic PCI registry. Outcome measures were incidence and prevalence of cvRF, including the Framingham Risk Score (FRS), at the time of admission for PCI. RESULTS: Age of non-ACS patients was higher than that of ACS patients, and age distribution slightly shifted toward older age in both groups (P for trend <0.001). There was no difference in FRS between the 2 groups; however, 10-year cardiovascular disease risk (%) remained higher in non-ACS than in ACS patients, decreasing over time. Diastolic blood pressure and high-density lipoprotein cholesterol were higher in non-ACS patients, but total cholesterol and low-density lipoprotein cholesterol were higher in ACS patients, with an improving trend over time. Prevalence of diabetes mellitus, hypertension, and history of hypercholesterolemia were higher in non-ACS patients, increasing over time. Smoking did not change over time. Use of most medications increased over time in both groups. CONCLUSIONS: Most cvRFs and their time trends exhibited statistically significant differences between ACS and non-ACS patients, except systolic blood pressure, body mass index, and history of myocardial infarction. A new risk-factor profile assessment may be needed for stratification of PCI patients according to ACS and non-ACS status. Clinical and public-health interventions should consider different approaches to ACS and non-ACS patients. PMID- 26671072 TI - BRAF(V600E) Is Correlated with Recurrence of Papillary Thyroid Microcarcinoma: A Systematic Review, Multi-Institutional Primary Data Analysis, and Meta-Analysis. AB - BACKGROUND: Given the increasing incidence of papillary thyroid carcinoma despite stable disease-specific mortality rates, the potential for the disease to reoccur is a key outcome to predict. The BRAF(V600E) mutation has been associated with recurrent disease in larger tumors. However, its correlation in papillary thyroid microcarcinoma (PTMC) is not clear in individual series. METHODS: The MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for studies including patients with PTMC undergoing initial surgical treatment. Studies with at least two years of follow-up, BRAF genotyping (the comparator), and recurrence as an outcome were included, as were unpublished primary data on 485 patients from two institutions. The metameter analyzed was odds ratio (OR) for recurrence between patients with BRAF(V600E) versus BRAF wild type (BRAFwt). RESULTS: The initial search identified 431 references. After screening of the abstracts for inclusion, 44 manuscripts were reviewed in full by two independent reviewers. Four published studies and primary data from two institutional cohorts were included in the final analysis. A meta-analysis of 2247 PTMC patients revealed that patients with a BRAF(V600E) mutation had a higher likelihood for recurrence (odds ratio 2.09 [confidence interval 1.31-3.33], p = 0.002). CONCLUSIONS: This meta-analysis shows that BRAF mutational status correlates with recurrence of PTMCs, highlighting the potential utility of genotyping in preoperative and postoperative planning. BRAF mutation may be helpful in risk-stratifying patients with PTMC for surgical management versus observation. PMID- 26671073 TI - Peer Rejection and Attention Deficit Hyperactivity Disorder Symptoms: Reciprocal Relations Through Ages 4, 6, and 8. AB - Attention deficit hyperactivity disorder (ADHD) predicts poor peer relationships. What remains unclear is whether poor peer relationships affect ADHD symptomatology. Hence, reciprocal effects of peer rejection and ADHD symptoms were examined in a community sample of 962 Norwegian children at ages 4, 6, and 8. Results showed that ADHD symptoms at age 4 predicted more peer rejection at age 6, and that peer rejection at age 4 predicted more symptoms at age 6. However, when conducting analyses on ADHD subtypes, hyperactivity-impulsivity and inattentiveness symptoms were adversely affected by peer rejection at ages 6 and 8, whereas peer rejection was unaffected by such symptoms, indicating that the effect of peer rejection on ADHD symptoms was most robust. Mediational relation were also identified. PMID- 26671075 TI - Cyclosporine Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy. AB - Operation Brain Trauma Therapy (OBTT) is a consortium of investigators using multiple pre-clinical models of traumatic brain injury (TBI) to bring acute therapies to clinical trials. To screen therapies, we used three rat models (parasagittal fluid percussion injury [FPI], controlled cortical impact [CCI], and penetrating ballistic-like brain injury [PBBI]). We report results of the third therapy (cyclosporin-A; cyclosporine; [CsA]) tested by OBTT. At each site, rats were randomized to treatment with an identical regimen (TBI + vehicle, TBI + CsA [10 mg/kg], or TBI + CsA [20 mg/kg] given intravenously at 15 min and 24 h after injury, and sham). We assessed motor and Morris water maze (MWM) tasks over 3 weeks after TBI and lesion volume and hemispheric tissue loss at 21 days. In FPI, CsA (10 mg/kg) produced histological protection, but 20 mg/kg worsened working memory. In CCI, CsA (20 mg/kg) impaired MWM performance; surprisingly, neither dose showed benefit on any outcome. After PBBI, neither dose produced benefit on any outcome, and mortality was increased (20 mg/kg) partly caused by the solvent vehicle. In OBTT, CsA produced complex effects with histological protection at the lowest dose in the least severe model (FPI), but only deleterious effects as model severity increased (CCI and PBBI). Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No positive treatment effects were seen on biomarker levels in any of the models, whereas significant increases in 24 h UCH-L1 levels were seen with CsA (20 mg/kg) after CCI and 24 h GFAP levels in both CsA treated groups in the PBBI model. Lack of behavioral protection in any model, indicators of toxicity, and a narrow therapeutic index reduce enthusiasm for clinical translation. PMID- 26671076 TI - Progressive multifocal leukoencephalopathy developing after liver transplantation showing marked neurological symptom improvement and arrest of further deterioration of imaging findings: A case report. PMID- 26671074 TI - Sustained intraocular VEGF neutralization results in retinal neurodegeneration in the Ins2(Akita) diabetic mouse. AB - Current therapies that target vascular endothelial growth factor (VEGF) have become a mainstream therapy for the management of diabetic macular oedema. The treatment involves monthly repeated intravitreal injections of VEGF inhibitors. VEGF is an important growth factor for many retinal cells, including different types of neurons. In this study, we investigated the adverse effect of multiple intravitreal anti-VEGF injections (200 ng/MUl/eye anti-mouse VEGF164, once every 2 weeks totalling 5-6 injections) to retinal neurons in Ins2(Akita) diabetic mice. Funduscopic examination revealed the development of cotton wool spot-like lesions in anti-VEGF treated Ins2(Akita) mice after 5 injections. Histological investigation showed focal swellings of retinal nerve fibres with neurofilament disruption. Furthermore, anti-VEGF-treated Ins2(Akita) mice exhibited impaired electroretinographic responses, characterized by reduced scotopic a- and b-wave and oscillatory potentials. Immunofluorescent staining revealed impairment of photoreceptors, disruptions of synaptic structures and loss of amacrine and retinal ganglion cells in anti-VEGF treated Ins2(Akita) mice. Anti-VEGF-treated WT mice also presented mild amacrine and ganglion cell death, but no overt abnormalities in photoreceptors and synaptic structures. At the vascular level, exacerbated albumin leakage was observed in anti-VEGF injected diabetic mice. Our results suggest that sustained intraocular VEGF neutralization induces retinal neurodegeneration and vascular damage in the diabetic eye. PMID- 26671077 TI - Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection. AB - OBJECTIVES: The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. METHODS: Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. RESULTS: 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n=107/109) and had involvement of upper limbs (83.5%; n=91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. CONCLUSIONS: Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA. PMID- 26671078 TI - Camptocormia and Pisa syndrome as manifestations of acute myasthenia gravis exacerbation. PMID- 26671079 TI - Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study. AB - The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 +/- 10 years) and 30 controls (mean age, 65 +/- 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid. PMID- 26671080 TI - Sphingomonas paucimobilis meningitis and ventriculitis in an immunocompromised host. PMID- 26671081 TI - Spontaneous downbeat nystagmus as a clue for the diagnosis of ataxia associated with anti-GAD antibodies. AB - Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the conversion of glutamic acid to the neurotransmitter gamma-amino butyric acid. Antibodies against GAD (anti-GAD-Ab) are associated with an array of autoimmune-related neurological conditions, such as stiff-person syndrome, cerebellar ataxia, epilepsy and limbic encephalitis. The clinical spectrum of ataxia associated with anti-GAD-Ab comprises slowly progressive cerebellar ataxia syndrome evolving in months or years, associated with cerebellar atrophy on brain MRI. There are few reports of patients with ataxia associated with anti-GAD-Ab presenting with abnormal ocular movements, such as downbeat nystagmus (DBN).We present two patients with ataxia associated with anti-GAD-Ab from a large series of ataxic subjects who presented with cerebellar ataxia combined with spontaneous DBN. All patients underwent a thorough neurological evaluation with the use of ataxia scales, brain MRI scans, cerebrospinal fluid examination, 18FDG-PET/CT scans, laboratory work-up with on coneural and immune encephalitis antibodies, serum and cerebrospinal fluid levels of anti-GAD-Ab, and the antibody specificity index to measure the intrathecal synthesis of anti-GAD-Ab. All patients were treated with cycles of intravenous immunoglobulin and had mild/partial ataxia improvement and no improvement of DBN. The finding of DBN may work as a diagnostic clue in the context of adult-onset non-hereditary ataxias. PMID- 26671082 TI - Demonstration of equivalence of a generic glatiramer acetate (GlatopaTM). AB - Glatiramer acetate (GA) has been available under the brand name Copaxone(r) for nearly two decades. Recently, the US Food and Drug Administration (FDA) approved the first generic GA, GlatopaTM, as fully substitutable for all indications for which Copaxone 20mg is approved; Glatopa also represents the first FDA-approved "AP-rated," substitutable generic for treating patients with MS. Glatiramer acetate is a complex mixture of polypeptides and, consequently, its characterization presented challenges not generally encountered in drug development. Despite its complexity, and without requiring any clinical data, approval was accomplished through an Abbreviated New Drug Application in which equivalence to Copaxone was evaluated across four criteria: starting materials and basic chemistry; structural signatures for polymerization, depolymerization, and purification; physicochemical properties; and biological and immunological properties. This article describes the rigorous overall scientific approach used to successfully establish equivalence between Glatopa and Copaxone, and presents key representative data from several of the comprehensive sets of physicochemical (structural) and biological (functional) assays that were conducted. PMID- 26671083 TI - Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients. AB - Hereditary spastic paraplegias (HSPs) consist of a heterogeneous group of genetically determined neurodegenerative disorders. Progressive lower extremity weakness and spasticity are the prominent features of HSPs resulting from retrograde axonal degeneration of the corticospinal tracts. Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs). Here, we present the results of genetic testing of the three mentioned SPG genetic types in a group of 216 unrelated Polish patients affected with spastic paraplegia. Molecular evaluation was performed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Nineteen novel mutations: 13 in SPAST, 4 in ATL1 and 2 in REEP1, were identified among overall 50 different mutations detected in 57 families. Genetic analysis resulted in the identification of molecular defects in 54% of familial and 8.4% of isolated cases. Our research expanded the causative mutations spectrum of the three most common genetic forms of HSPs found in a large cohort of probands originating from the Central Europe. PMID- 26671084 TI - The effect of B-cell depletion in the Theiler's model of multiple sclerosis. AB - B cell depletion (BCD) is being considered as a treatment for multiple sclerosis (MS), but there are many uncertainties surrounding the use of this therapy, such as its potential effect in individuals with concurrent viral infections. We sought to discover what effect BCD, induced by an anti-CD20 monoclonal antibody, would have on Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Mice were injected with the anti-CD20 monoclonal antibody 5D2, 14 days before or 14 days after infection with TMEV. Efficacy of depletion of B cells was assessed by flow cytometry of CD19(+) cells. Mouse disability was measured by Rotarod, viral load was measured by real time PCR for TMEV RNA. Binding and neutralizing antibody levels were determined in sera and CSF by ELISA, and in CNS by real time PCR for IgG RNA. Inflammation, microglial activation, axonal damage and demyelination were assessed using immunohistochemistry. 5D2-induced BCD was confirmed by demonstration of nearly absent CD19(+) cells in the blood and lymphoid tissue. Systemic and CNS antibody responses were suppressed during 5D2 treatment. Higher viral loads were detected in 5D2-treated mice than in controls, and the viral levels correlated negatively with IgG production in the brain. Overall, 5D2 caused worsening of the early encephalitis and faster progression of disability, as well as exacerbation of the pathology of TMEV-IDD at the end stage of the disease. These data indicate that BCD in humans might worsen CNS viral infections and might not improve disability accrual in MS. PMID- 26671086 TI - Varicella zoster-induced magnetic resonance imaging abnormalities of the trigeminal nucleus. PMID- 26671085 TI - Protein phosphatase 2A (PP2A) activation promotes axonal growth and recovery in the CNS. AB - Current treatments to restore neurological deficits caused by axonal disconnection following central nervous system (CNS) injury are extremely limited. Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, dephosphorylates collapsin response mediator protein-2 (CRMP2) in the developing CNS. In our study, we found that the major CNS inhibiting substrates, including chondroitin sulfate proteoglycans (CSPGs) and myelin associated glycoproteins (MAG), activated epidermal growth factor receptor (EGFR), but inactivated PP2A and downstream CRMP2. Both EGFR inactivation and PP2A activation promoted axon elongation in vitro in the presence of inhibitory substrates. EGFR blockage by AG1478 selectively attenuated the inactive form of PP2A in pY307 phosphorylation, thus increasing PP2A activity. EGFR activation by EGF attenuated PP2A activity, whereas mutation of Y307 to phenylalanine abolished the effect. Furthermore, PP2A activity was down regulated immediately after spinal cord injury (SCI) in rats. Chronic application of d-erythro-sphingosine (DES), the PP2A agonist, to spinal cord-lesioned rats enhanced the activity of this phosphatase and dephosphorylated CRMP2 around the lesion. PP2A activation induced significant axon sprouting in the lesioned spinal cord and promoted function recovery after SCI. These findings suggest that PP2A works downstream of EGFR and dephosphorylates CRMP2 after CNS injury. Therefore, therapies targeting PP2A may be effective following SCI. PMID- 26671087 TI - Neuropsychological impairment in childhood absence epilepsy: Review of the literature. AB - AIM: Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence seizures in school age children. Although it is commonly considered to have a good prognosis, with a good response to antiepileptic drugs, recent studies questioned this traditional view of a "benign" disorder, in particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological involvement in patients affected by CAE. METHODS: A literature search was carried out in PubMed's and Medline's databases for all relevant studies published between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specific review articles, systematic reviews, textbooks and case reports were examined for any further publications. RESULTS: In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions have been reported to be mildly impaired. Data regarding memory are still conflicting. DISCUSSION: Given the neuropsychological deficits in many CAE patients which significantly affect their quality of life, CAE should not be considered entirely "benign". An early identification of neuropsychological dysfunction in CAE children is essential for appropriate treatment. PMID- 26671088 TI - Toll-like receptor 4 (TLR4) is correlated with delayed cerebral ischemia (DCI) and poor prognosis in aneurysmal subarachnoid hemorrhage. AB - Toll-like receptor 4 (TLR4) is one of key players in regulation of inflammation. Animal experiments have suggested an important role of TLR4 in the pathophysiology of subarachnoid hemorrhage (SAH). In present study, TLR4 is investigated in clinical SAH patients to explore its clinical significance. 30 patients with aneurysmal subarachnoid hemorrhage (aSAH) and 20 healthy control patients (HC) were enrolled in this prospective study. Blood samples were collected on days 1, 3 and 7 after admission. TLR4 expression level on cell surface of peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and presented as mean fluorescence intensity (MFI). Patients were clinically assessed every day after admission to monitor the occurrence of delayed cerebral ischemia (DCI). Participants were followed up until completion of 3 months after SAH. Functional outcome was defined by modified Rankin score (mRs). Results show that SAH patients presented a significantly higher TLR4 levels on days 1 and 3 post SAH compared to HC; TLR4 levels in SAH patients on day 1 was highest compared with that on days 3 and 7 and in HC. TLR4 of SAH patients on day 7 declined to the level showing no significant difference with that of HC. In patients with Hunt-Hess grades I-III lower TLR4 levels were observed. Patients with DCI showed significantly higher TLR4 levels than those without DCI. High TLR4 levels were statistically significantly associated with poor functional outcome after 3 months. Logistic regression analysis showed that TLR4 level on day 1 was independent predictor for DCI and 3-month poor neurological outcome of aneurysmal SAH patients. In summary, admission TLR4 level on PBMCs (day 1) is an independent risk factor to predict the occurrence of DCI and 3-month poor neurological outcome in aneurysmal SAH patients. PMID- 26671089 TI - A multicenter, prospective, observational study of warfarin-associated intracerebral hemorrhage: The SAMURAI-WAICH study. AB - BACKGROUND: Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated. METHODS: WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year. RESULTS: Of 50 WAICH patients (31 men, 73 +/- 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25-9), 4 (2-5.5) and 6 (3-11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1 hour increase; OR 0.55, 95% CI 0.19-0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n=47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4-6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05-227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10-1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07-1.55), were independently associated with unfavorable outcome. CONCLUSIONS: PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome. PMID- 26671090 TI - Analysis of neoplastic lesions in magnetic resonance imaging using self organizing maps. AB - OBJECTIVE: To provide an improved method for the identification and analysis of brain tumors in MRI scans using a semi-automated computational approach, that has the potential to provide a more objective, precise and quantitatively rigorous analysis, compared to human visual analysis. BACKGROUND: Self-Organizing Maps (SOM) is an unsupervised, exploratory data analysis tool, which can automatically domain an image into selfsimilar regions or clusters, based on measures of similarity. It can be used to perform image-domain of brain tissue on MR images, without prior knowledge. DESIGN/METHODS: We used SOM to analyze T1, T2 and FLAIR acquisitions from two MRI machines in our service from 14 patients with brain tumors confirmed by biopsies--three lymphomas, six glioblastomas, one meningioma, one ganglioglioma, two oligoastrocytomas and one astrocytoma. The SOM software was used to analyze the data from the three image acquisitions from each patient and generated a self-organized map for each containing 25 clusters. RESULTS: Damaged tissue was separated from the normal tissue using the SOM technique. Furthermore, in some cases it allowed to separate different areas from within the tumor--like edema/peritumoral infiltration and necrosis. In lesions with less precise boundaries in FLAIR, the estimated damaged tissue area in the resulting map appears bigger. CONCLUSIONS: Our results showed that SOM has the potential to be a powerful MR imaging analysis technique for the assessment of brain tumors. PMID- 26671091 TI - Acute bilateral vestibulocochlear neuritis following cultured cell vaccine administration for rabies post-exposure prophylaxis. PMID- 26671092 TI - Ocular flutter and ataxia without cognitive impairment associated with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT). PMID- 26671093 TI - Cortical event-related potentials in Alzheimer's disease and frontotemporal lobar degeneration. AB - BACKGROUND: The aim of the present study was to evaluate changes in event-related evoked potentials (ERPs) in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). METHODS: A total of 42AD patients, 29 behavioral variant frontotemporal dementia (bvFTD) patients, and 30 healthy controls were examined. The subjects underwent neuropsychological tests and cognitive (N200 and P300) ERP examination. The amplitudes and latencies of the cortical potentials were compared among AD and bvFTD patients and control subjects. RESULTS: No differences in the ERP latencies and amplitudes for the N200 component were observed among the groups. AD patients exhibited significantly longer latencies of P300 at both Pz (p=0.002) and Cz (p=0.007) compared with the controls. Patients with bvFTD displayed longer P300 latencies at Pz (p=0.046) and a smaller amplitude at both Pz (p=0.000) and Cz (p=0.23) than the controls. CONCLUSIONS: The results of the present study confirm the relevance of ERPs in evaluating cognitive disorders. These non-invasive examinations have the potential to contribute to the diagnosis of AD and bvFTD. PMID- 26671094 TI - Cognitive evaluation by tasks in a virtual reality environment in multiple sclerosis. AB - BACKGROUND: The assessment of cognitive impairment in multiple sclerosis (MS) requires large neuropsychological batteries that assess numerous domains. The relevance of these assessments to daily cognitive functioning is not well established. Cognitive ecological evaluation has not been frequently studied in MS. OBJECTIVES: The aim of this study was to determine the interest of cognitive evaluation in a virtual reality environment in a sample of persons with MS with cognitive deficits. METHODS: Thirty persons with MS with at least moderate cognitive impairment were assessed with two ecological evaluations, an in-house developed task in a virtual reality environment (Urban DailyCog(r)) and a divided attention task in a driving simulator. Classical neuropsychological testing was also used. RESULTS AND CONCLUSION: Fifty-two percent of the persons with MS failed the driving simulator task and 80% failed the Urban DailyCog(r). Virtual reality assessments are promising in identifying cognitive impairment in MS. PMID- 26671095 TI - Cyclooxygenase-2 gene polymorphisms and risk of Alzheimer's disease: A meta analysis. AB - PURPOSE: Cyclooxygenase-2 (COX-2) is one of the key enzymes in the synthesis of prostaglandins, and plays a pivotal role in inflammatory response. Recent studies have suggested cyclooxygenase-2 is involved in the pathogenesis of Alzheimer's disease (AD). However, the relationship between COX-2 gene polymorphisms (-765G>C rs20417, -1195A>G rs689466) and Alzheimer's disease risk is not conclusive. We conducted a meta-analysis to systematically examine and to clarify the association between the two SNPs and AD risk. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library and CBMdisc were searched in July 2015 to identify eligible studies. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. RESULTS: A total of 7 case-control studies about COX-2 rs20417 polymorphisms and AD risk, and 3 studies about COX-2 rs689466 and AD risk were included in this meta-analysis. For rs20417 (-765G>C), there was a significant association between rs20417 and AD, and the risk for AD decreased in all gene models (C allele versus G allele: OR=0.570 CI 0.484-0.672; CC+GC versus GG: OR=0.568 CI 0.470-0.686; CC versus GC+GG: OR=0.357, CI 0.217-0.587; CC versus GG: OR=0.311, CI 0.189-0.514; GC versus GG: OR=0.613 CI 0.503-0.746). CONCLUSION: C-allele of rs20417 (-765G>C) polymorphism was associated with reduced risk of AD, and might be a protective factor. Because of the limit sample and heterogeneity, the association between rs689466 polymorphism and AD risk should be treated with caution. To further confirm this relationship, larger scale and better-designed studies should be conducted in the future. PMID- 26671096 TI - Rituximab in Turkish neuromyelitis optica patients with limited response to other immunosuppressants. PMID- 26671097 TI - Vitamin D status and vascular dementia due to cerebral small vessel disease in the elderly Asian Indian population. AB - Vitamin D plays vital roles in human health and recent studies have shown its beneficial effect on brain functioning. The present study was designed to evaluate the association of vitamin D with vascular dementia (VaD) due to cerebral small vessel disease (SVD) in Asian Indian population. 140 VaD patients aged >= 60 years with neuroimaging evidence of SVD, and 132 age and gender matched controls, were investigated. Vitamin D status was estimated by measuring serum 25-hydroxy vitamin D. Logistic regression model revealed that deficient levels of vitamin D (<12 ng/ml) were associated with 2.2-fold increase in odds of VaD after adjustment with covariates. Hypertension was independently associated with 11.3-fold increased odds of VaD. In hypertensives with vitamin D deficiency and insufficiency (12-20 ng/ml), the odds were increased to 31.6-fold and 14.4 fold, respectively. However, in hypertensives with vitamin D sufficiency (>20 ng/ml), the odds of VaD were increased by 3.8-fold only. Pearson correlation showed that serum vitamin D was inversely associated with systolic and diastolic blood pressure (r=-0.401 and -0.411, p<0.01, respectively) in vitamin D-deficient subjects. Since the combined presence of hypertension and vitamin D deficiency increases the probability of developing VaD, screening for vitamin D status in addition to regular monitoring of blood pressure, could reduce the risk of VaD associated with cerebral SVD in the elderly Asian Indian subjects. PMID- 26671098 TI - Task-shifting training improves stroke knowledge among Nigerian non-neurologist health workers. AB - BACKGROUND: The increasing stroke burden in sub-Saharan Africa far outstrips the availability of skilled human resource to provide timely and efficient acute, rehabilitative and preventive services. The objective of this study was to examine the impact of a short-term task-shifting stroke training program on the stroke knowledge of a cohort of Nigerian non-neurologist health workers (NNHWs). METHODS: Utilizing a quasi-experimental design, NNHWs drawn from 53 local government areas of Ogun and Oyo states participated in an intensive, multicomponent one-day stroke workshop. Stroke knowledge was evaluated before and after the training using a self-administered questionnaire. RESULTS: Out of a total of 210 NNHWs who participated in the session, 116 (55.2%) completed the pre workshop questionnaire survey of stroke knowledge while 191 (91.0%) completed the post-workshop questionnaire survey. There were no statistically significant differences in the distribution of the age, gender and professional categories of the two groups. The participants' knowledge was significantly increased at the end of the training about stroke risk factors (p<0.001), stroke symptoms (p<0.001) and how stroke develops (p=0.009). The proportion of respondents who understood the FAST mnemonic increased from 10.3% before the training to 90.6% at the end of the training (p<0.001). The professional category of participants was associated with knowledge gain about swallowing test and thrombolysis. CONCLUSION: Our data support the effectiveness of stroke-specific task-shifting training for non-neurologist health workers in a low resource setting. Interim studies with intermediate outcomes are needed to show that improved knowledge results in better care despite resource limitation. Randomized controlled trials will be useful to confirm findings and translate knowledge improvement into practical intervention. PMID- 26671099 TI - Motor and somatosensory abnormalities are significant etiological factors for adolescent idiopathic scoliosis. AB - OBJECTIVE: In adolescent idiopathic scoliosis (AIS), we explore the role of lateralized motor and somatosensory abnormalities as a possible etiological factor. METHODS: Intraoperative transcranial electrical stimulation was performed in 15 AIS and 14 adult degenerative scoliosis (ADS) patients. Inter-side motor output balance (MOB) by comparing the ratios of right to left motor evoked potentials (MEP) amplitudes, and inter-side motor output excitability (MOE) computed with MEP amplitude, was determined separately for both patients groups. For somatosensory evoked potentials (SSEP), peak to peak P37 amplitudes from right and left lower limb SSEP and inter-side P37 amplitude ratios were obtained. RESULTS: Inter-side MOB was significantly asymmetric in AIS patients, contributed mainly by inter-side MOB changes in the upper than the lower limbs. Inter-side MOE comparisons of ipsilateral and contralateral MEP amplitudes were significantly different between AIS and ADS patients. Mean upper limb MEP amplitudes were significantly reduced in AIS patients. Amplitude of the right upper limb MEPs were positively correlated with inter-side MEP ratio. AIS patients show larger mean MEP amplitudes on the same side as the scoliotic curve. Overall, no correlation of Cobb's angle or total levels of scoliosis involvement with inter-side MOB and MOE parameters was found. Inter-side SSEP ratios were significantly higher in AIS patients. CONCLUSIONS: Primary dysfunctional and distributed motor output contributing to abnormalities of inter-side MOB and MOE changes involving the upper limbs is evident in AIS. Simultaneous but independent somatosensory and motor observations seen these patients suggest a central mechanism as an etiological factor. PMID- 26671100 TI - Preemptive therapy with ganciclovir and cytomegalovirus hyperimmune globulin delayed the onset of Epstein-Barr virus-associated post-transplant acute limbic encephalitis. PMID- 26671101 TI - Risk factors for cognitive and functional change in one year in patients with Alzheimer's disease dementia from Sao Paulo, Brazil. AB - Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimer's disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores. Established cerebrovascular risk factors had no independent effects over cognitive or functional change, but their combinations led to cognitive improvement, possibly related to enhanced cerebral perfusion in late life. Cholinesterase inhibitors improved caregiver burden. Enhanced instrumental functionality and steeper cognitive decline by the use of anti-psychotics might be attributed to improved behavioural symptoms and neuropsychiatric side effects, respectively. Each copy of APOE-epsilon4 (beta=-0.102) led to cumulative decreased participation in physical activities (rho=0.015). These results might impact public health policies and the interpretation of clinical trials for AD. PMID- 26671102 TI - Experimental evidence that overexpression of NR2B glutamate receptor subunit is associated with brain vacuolation in adult glutaryl-CoA dehydrogenase deficient mice: A potential role for glutamatergic-induced excitotoxicity in GA I neuropathology. AB - Glutaric aciduria type I (GA I) is biochemically characterized by accumulation of glutaric and 3-hydroxyglutaric acids in body fluids and tissues, particularly in the brain. Affected patients show progressive cortical leukoencephalopathy and chronic degeneration of the basal ganglia whose pathogenesis is still unclear. In the present work we investigated parameters of bioenergetics and redox homeostasis in various cerebral structures (cerebral cortex, striatum and hippocampus) and heart of adult wild type (Gcdh(+/+)) and glutaryl-CoA dehydrogenase deficient knockout (Gcdh(-/-)) mice fed a baseline chow. Oxidative stress parameters were also measured after acute lysine overload. Finally, mRNA expression of NMDA subunits and GLT1 transporter was determined in cerebral cortex and striatum of these animals fed a baseline or high lysine (4.7%) chow. No significant alterations of bioenergetics or redox status were observed in these mice. In contrast, mRNA expression of the NR2B glutamate receptor subunit and of the GLT1 glutamate transporter was higher in cerebral cortex of Gcdh(-/-) mice. Furthermore, NR2B expression was markedly elevated in striatum of Gcdh(-/-) animals receiving chronic Lys overload. These data indicate higher susceptibility of Gcdh(-/-) mice to excitotoxic damage, implying that this pathomechanism may contribute to the cortical and striatum alterations observed in GA I patients. PMID- 26671103 TI - The susceptibility vessel sign containing two compositions on 3-tesla T2* weighted image and single corticosubcortical infarct on diffusion-weighted image are associated with cardioembolic stroke. AB - BACKGROUND: Although accurate diagnosis of the ischemic stroke subtype is one of the most important factors for selection of therapeutic approach, it is sometimes difficult at the time of admission. We previously reported that susceptibility vessel sign (SVS) with two layers (termed two-layered SVS) on 3-tesla-T2* weighted image (T2*-WI) might be useful to predict cardioembolic stroke in patients with cerebral major vessel occlusion. We studied about biomarkers on magnetic resonance imaging (MRI), including two-layered SVS for diagnosing cardioembolic stroke. METHODS: We included 132 ischemic stroke patients within 24h from onset who suffered internal carotid artery or middle cerebral artery occlusion due to cardioembolic stroke (group CE) or large artery atherosclerosis (group LAA). We studied about biomarkers on MRI such as two-layered SVS and abnormal finding patterns of diffusion-weighted image (DWI) for diagnosis of cardioembolic stroke in addition to laboratory data, physiological examination, and clinical findings. RESULTS: In this study, 132 patients (72 men and 60 women, age 74.5 +/- 12.1 years) were included. Of these, 63 (47.7%) were cardioembolic stroke. In univariate analysis, frequency of comorbid atrial fibrillation, presence of two-layered SVS on T2*-WI and that of single corticosubcortical infarct on DWI, intima-media thickness were significantly higher in group CE. In multivariate analysis, the presence of two-layered SVS and single corticosubcortical infarct were associated with cardioembolic stroke (odds ratio, two-layered SVS, 30.08, p<0.001; single corticosubcortical infarct, 15.78, p<0.001). CONCLUSION: Biomarkers associated with cardioembolic stroke may be two layered SVS on T2*-WI and single corticosubcortical infarct on DWI. PMID- 26671104 TI - Onset-adjusted incidence of multiple sclerosis in the Girona province (Spain): Evidence of increasing risk in the south of Europe. AB - BACKGROUND: Recent studies show an increasing incidence of multiple sclerosis (MS) in southern Europe. Although by its geographical location and genetic characteristics Spain is expected to be similar to other southern European regions, data on incidence are scarce. The aim of this study was to determine the onset-adjusted incidence of MS in the Girona province in Catalonia (Spain). METHODS: A prospective incidence study pooling data from the population-based Catalonia MS Registry was performed. Incident cases were defined as patients who had the onset of symptoms compatible with a clinically isolated syndrome (CIS) suggestive of MS in 2009 and fulfilled McDonald-2005 criteria during follow-up. Age- and sex-specific incidence rates were obtained. RESULTS: The Registry included 182 patients residing in Girona that presented a CIS from January 2009 to December 2013. Fifty one patients had the onset of symptoms in 2009, of whom 27 patients fulfilled the diagnostic criteria, giving an incidence of 3.6 per 100,000 (CI 95% 2.4-5.3) inhabitants; 4.3 (CI 95% 2.5-7.1) for women and 2.9 (CI 95% 1.4-5.2) for men. The age-adjusted incidence rate for the European population was 3.29 (CI 95% 3.2-3.3). CONCLUSION: The incidence estimation derived in this study is consistent with recent epidemiological data of MS in southern Europe suggesting an increase in incidence in this region. PMID- 26671105 TI - Central nervous system (CNS) cancer in children and young people in the European Union and its involvements with socio-economic and environmental factors. AB - Malignant central nervous system (CNS) tumors are the leading cause of death by cancer in children and the second commonest pediatric cancer type. Despite several decades of epidemiologic research, the etiology of childhood CNS tumors is still largely unknown. A few genetic syndromes and therapeutic ionizing radiation are thought to account for 5-10% of childhood cancer, but the etiology of other cases remains unknown. Nongenetic causes, like environmental agents, are thought to explain them. However, as very few epidemiologic studies have been conducted, it is not surprising that nongenetic risk factors have not been detected. The biggest difference between cancers for which there are good etiologic clues and those for which there are none could be the number of relevant studies. This study, which covers the 1980-2011 period, identified links between CNS cancer evolution and the socio-economic and environmental indicators in the same space and time limits in the European Union. PMID- 26671106 TI - Diagnostic yield of the palmomental reflex in patients with suspected frontal lesion. AB - BACKGROUND: The purpose of this study was to determine the diagnostic value of the palmomental reflex in order to identify frontal lesions in neurological outpatients. METHODS: Two hundred twenty-six neurological patients with suspected intracranial lesion with an indication for magnetic resonance imaging (MRI) were included. All patients underwent the same MRI protocol. The reflex was elicited by trained and standardized nurses, and was evaluated by two neurologists. The evaluation was blind and independent. The test's accuracy was calculated. The Kappa coefficient was used to calculate the interobserver and intra-observer reliability. RESULTS: The interobserver reliability between neurologists was 0.53 with 93% of agreement (p<0.001). The diagnostic accuracy measures were as follow: sensitivity of 19%, specificity of 93%, positive predictive value of 30%, negative predictive value of 88%, positive likelihood ratio of 2.7 and negative likelihood ratio of 0.87. The area under the curve was 0.56. CONCLUSION: The palmomental reflex is associated with frontal structural lesions but the sensitivity is low, indicating a high percentage of frontal lesions with a negative reflex. When the test is used on its own, it is insufficient to detect frontal damage. PMID- 26671107 TI - 123I-FP-CIT SPECT in the differential diagnosis between dementia with Lewy bodies and other dementias. AB - AIM: To systematically review the utility of dopamine system imaging using 123I FP-CIT SPECT in the differential diagnosis between dementia with Lewy bodies (DLB) and other dementia syndromes. METHODS: We searched MEDLINE, CENTRAL and ClinicalTrials.gov to identify studies reporting enough data to determine accuracy measure of 123I-FP-CIT SPECT in differentiating between DLB and other dementia syndromes. Studies including patients with Parkinson's disease or other parkinsonisms associated with abnormal DAT imaging were excluded. The methodological quality of studies was evaluated with QUADAS-2. RESULTS: Eight studies were included. Studies adopting a clinical diagnosis as a reference standard showed sensitivity and specificity values of DaTSCAN in differentiating between DLB and non-DLB dementia syndromes (all subtypes, AD and FTD) consistently higher than 80%, both considering a visual and a semiquantitative analysis. The meta-analyses from the three studies using a neuropathological reference standard yielded sensitivity and specificity values higher than those adopting a clinical diagnostic reference. CONCLUSIONS: 123I-FP-CIT SPECT can represent an accurate method to differentiate between DLB and other dementia syndromes. However, most data in the literature derive from studies adopting the clinical diagnosis as the reference diagnostic standard and which are therefore intrinsically unable to demonstrate an accuracy of DAT imaging above that of careful clinical diagnosis alone. The very few studies providing information on the neuropathologic correlation for the DaTSCAN findings show however high sensitivity and specificity values, suggesting that SPECT scan is more accurate than clinical diagnosis and may prove useful in supporting the clinical diagnosis of DLB. PMID- 26671108 TI - No evidence for a role of Ile587Val polymorphism of EIF2B5 gene in multiple sclerosis in Kashmir Valley of India. AB - Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the nervous system with a profound genetic element. It is already known that alterations in Eukaryotic Translation Initiation Factor 2B (EIF2B) gene encoding the five subunits of eIF2B complex cause Vanishing White Matter (VWM) disease of the brain and emerging evidences have advocated certain resemblances between MS and VWM in terms of clinical and epidemiological characteristics, thus validating the association study between EIF2B and MS. Moreover, a recent study has implicated EIF2B5 Ile587Val (rs843358) polymorphism as a susceptibility factor for MS. In order to investigate the association of EIF2B5 Ile587Val polymorphism with MS susceptibility in Kashmir region in India, we screened EIF2B5 Exon 13 in 30 MS patients and 65 controls (a total of 95 participants). During the present course of study, we could not find statistically significant difference in the frequency of Ile587Val between MS patients and controls, thus indicating that such alteration does not appear to influence MS development in Kashmiri population. Our results provide evidence against a major role for Ile587Val polymorphism in MS susceptibility. PMID- 26671109 TI - Expression and clinical role of RBQ3 in gliomas. AB - RBQ3, also known as RBBP5 (RB-binding protein 5), was an RB-binding protein. Besides, it was one of core components of MLL1 (mixed lineage leukemia 1), which were required for H3K4 methyltransferase activity. MLL1 dysfunction was found to be associated with the progression of some cancers such as acute leukemias. However, the precise role of RBQ3 in tumor progression remains obscure. In this study, we explored the expression and clinical role of RBQ3 in gliomas. Our results showed that RBQ3 was significantly upregulated in clinical glioma specimens by Western blot and immunohistochemistry. Moreover, its level was significantly associated with the pathology grades. High RBQ3 expression was suggested to be an independent prognostic factor for glioma patients' survival by univariate and multivariate analyses. Serum starvation and refeeding assay indicated that the expression of RBQ3 increased 8h after serum-stimulation, together with percentage of cells at S phase. In addition, knockdown of RBQ inhibited U87-MG cell proliferation with CCK8 kit, flow cytometry assays and colony formation analyses; while the depletion of RBQ3 induced the apoptosis of U87-MG cells. All the findings suggested that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents. PMID- 26671110 TI - Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls. AB - PURPOSE: The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). METHODS AND MATERIALS: 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. RESULTS: 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4mm in Rb patients and 6.3mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1mm(3) and was 87.6mm(3) in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2mm and the mean volume in TRb patients was 453.3mm(3). The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). CONCLUSION: Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma. PMID- 26671111 TI - Gastrointestinal dysfunction in postural tachycardia syndrome. AB - BACKGROUND: Postural tachycardia syndrome (POTS) is a dysautonomia defined by an exaggerated increase in heart rate upon changing posture. It is associated with disturbances involving multiple organ systems, including neurologic, dermatologic, and gastrointestinal (GI) symptoms. Previous studies identified GI complaints in these patients and showed gastric emptying and electrical activity abnormalities. However, the full spectrum of GI symptoms and their impact on quality of life remains unclear. METHODS: A 30-question survey of GI symptoms was collected from 28 patients with POTS seen in the Boston Medical Center Autonomic Clinic. Answers were recorded on a Likert rating scale. Symptoms were positive if patients answered "strongly agree" or "agree" and negative if they answered "strongly disagree" or "disagree." Responses were collected and analyzed. RESULTS: The most commonly reported GI symptoms were nausea (86%), irregular bowel movements (71%), abdominal pain (70%), and constipation (70%). Additionally, 82% of patients reported having GI symptoms more than once per week, and 71% reported having seen a GI specialist, and symptoms did not improve with changes in position. Twelve patients had undergone a gastric emptying study, and six of these patients reported receiving a diagnosis of gastroparesis or delayed gastric emptying. CONCLUSIONS: GI disturbances are common, frequent, and prolonged in patients with POTS, likely impacting quality of life. Given the importance of the enteric nervous system to normal GI functioning, the same autonomic impairment leading to POTS may result in abnormal gut motility and ultimately subjective GI discomfort. PMID- 26671112 TI - Correlation of the VEMP score, ambulation and upper extremity function in clinically isolated syndrome. AB - OBJECTIVE: To investigate the correlation of the vestibular evoked myogenic potential (VEMP) score with Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test (PASAT) and EDSS in patients with multiple sclerosis (MS). METHODS: This prospective, cross sectional study included 52 patients with clinically isolated syndrome (CIS). Cervical VEMP (cVEMP) and ocular VEMP (oVEMP), analyzed in the form of the cVEMP, oVEMP and VEMP scores, T25FW, 9HPT, PASAT and Expanded Disability Status Scale (EDSS) were performed. RESULTS: The only predictor of walking impairment in this study was general disability as measured by the EDSS, after controlling for age, gender, PASAT and EDSS the effect of VEMP score was non-significant (p=0.419). 9HPT of the dominant hand did not correlate with the oVEMP score (rs=0.258, p=0.065), however after controlling for age, gender, PASAT and EDSS, the effect of the oVEMP score on 9HPT of the dominant hand was statistically significant (p=0.017). After controlling for age, gender and oVEMP score, the effect of the PASAT on 9HPT variable for the non-dominant hand was statistically significant (p=0.001). CONCLUSION: We found possible effects of brainstem dysfunction on walking impairment, however they were not seen after correction for EDSS and cognitive dysfunction. On the other hand, dominant hand function seems to be influenced by upper brainstem dysfunction measured with oVEMP, while cognitive dysfunction is related to non-dominant hand function. PMID- 26671113 TI - Serum neuron specific enolase level as a predictor of prognosis in acute ischemic stroke patients after intravenous thrombolysis. AB - OBJECTIVE: Serum neuron specific enolase (NSE) concentrations are significantly correlated with stroke severity and clinical outcome in ischemic stroke patients. We aimed to determine whether the serum levels of neuron specific enolase in acute ischemic stroke (AIS) patients after intravenous thrombolysis are associated with stroke severity, and indicative of favorable outcome. METHODS: We prospectively analyzed the serum neuron specific enolase levels with for 67 subjects with AIS patients treated with intravenous recombinant tissue type plasminogen activator (rtPA) within 4.5h from symptom onset. Neurologic deficit was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90days according to the modified Rankin Scale. RESULTS: Neuron specific enolase levels correlated with National Institutes of Health Stroke Scale score 24h after rtPA bolus (R=0.342, p=0.005). Regarding the 67 included patients, 32 (47.8%) reached favorable outcome. They had a lower NIHSS score on admission (p=0.000) and at 24h after rtPA bolus (p=0.000), and had lower levels of neuron specific enolase (p=0.006). But only NIHSS score at 24h after rtPA bolus rather than neuron specific enolase level was an independent predictor for favorable outcome. CONCLUSION: We found that after treatment with intravenous rtPA therapy, lower serum neuron specific enolase levels were associated with favorable outcome, which may be confounded by the link to NIHSS score. PMID- 26671114 TI - Impaired vascular endothelial function in patients with restless legs syndrome: a new aspect of the vascular pathophysiology. AB - BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder in which patients feel unpleasant leg sensations and the urge to move their legs during rest, particularly at night. Leg movement improves these symptoms. Although several studies have demonstrated an association between cardiovascular disease and RLS, the mechanisms underlying this relationship remain unclear. Recent studies have shown changes in the peripheral microvasculature, including altered blood flow and capillary tortuosity, and peripheral hypoxia. Vascular endothelial dysfunction can be assessed noninvasively with ultrasound measurements of brachial artery flow-mediated dilatation (FMD). Therefore, this study investigated FMD in RLS patients to determine the involvement of microvascular alterations in this disorder. METHODS: The study enrolled 25 drug-naive RLS patients and 25 sex- and age-matched controls and compared the FMD values of the two groups. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group. RESULTS: FMD was significantly lower in the RLS patients (6.6 +/- 1.2%) compared to the controls (8.4 +/- 1.8%; p<0.05) and the RLS patients showed a weak, negative correlation between RLS severity and FMD (r=-0.419, p=0.04). Multivariate linear regression analysis revealed that RLS (B= 1.87, 95% confidence interval [CI] -2.72 to -1.02; p<0.001) and age (B=-0.06; 95% CI -0.12 to -0.02; p<0.001) were significantly and inversely correlated with FMD. CONCLUSIONS: This study demonstrated that RLS patients have poorer vascular endothelial function than normal healthy subjects and provides further evidence supporting the involvement of peripheral systems in the generation of RLS. PMID- 26671115 TI - Natalizumab continuation during pregnancy in a patient with previous severe IRIS syndrome. PMID- 26671116 TI - Do longer necks predispose to Hirayama disease? A comparison with mimics and controls. AB - BACKGROUND: Dynamic changes in cervical spine during flexion is a proposed mechanism for Hirayama disease [HD], a localized form of anterior horn cell disorder. Apparent shortening of dura as compared to vertebral column leading to dural shift on flexion is considered to be the primary mechanism in this hypothesis. Whether this disproportion is a result of short dura or longer cervical segment is not known and neck length has not been studied in HD. Also, all patients with segmental motor weakness and wasting of upper limbs do not show dural changes; hence comparative evaluation of HD and its mimics is important. MATERIAL AND METHODS: Patients with segmental wasting and weakness limited to upper limbs were subjected to flexion MRI. A special pillow was designed to provide fixed flexion angle of 35 degrees . Patients showing dural changes formed the HD group while rest formed the non-HD group [mimics]. Both groups were analyzed on clinical, electrophysiological and radiological parameters. Whole spine to neck ratio of patients in HD group was compared to the non-HD group and age matched controls. RESULTS AND CONCLUSIONS: Patients with HD had longer cervical segments as compared to the non-HD group and age matched controls [p=0.001]. The longer cervical segment, in combination with dural changes probably contributes to the pathophysiology of dynamic flexion hypothesis of HD and the onset around the growth spurt. Patients with HD had cold paresis and finger extensors were consistently weaker than flexors. Apart from longer necks, cold paresis and pattern of weakness may help to differentiate HD from its mimics. PMID- 26671117 TI - Hepatic artery vasoconstriction associated with reversible cerebral vasoconstriction syndrome. PMID- 26671118 TI - Comparison of different stimulation parameters of repetitive transcranial magnetic stimulation for unilateral spatial neglect in stroke patients. AB - OBJECTIVE: In this study three different stimulation parameters of repetitive transcranial magnetic stimulation (rTMS) were tested to compare the efficacy of continuous theta burst stimulation (continuous TBS) for rehabilitation of unilateral spatial neglect (USN) in stroke patients. METHODS: Carefully selected cohort of thirty-eight stroke patients were randomly assigned to three treatment groups (1 Hz group, 10 Hz group and continuous TBS group) and sham group. Intervention in patients in the treatment group consisted of rTMS, while patients in the sham group received pseudo-stimulation for two weeks. All patients were administered star cancellation and line bisection tests at 4 different time points of the study. Further, all study subjects in the three treatment groups and sham group underwent diffusion-tensor imaging (DTI) at the beginning and at the end of treatment to calculate fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Among the three stimulation parameters, star cancellation and line bisection tests revealed significant differences in outcomes at the end of treatments and one month after the end of treatments, compared to beginning of the treatments. Importantly, continuous TBS group patients displayed the best curative effect, based on behavioral scoring, at one month after end of the treatments, followed by the 1Hz group and 10 Hz group. DTI results showed a significant increase in FA and MD in superior longitudinal fasciculus, superior occipitofrontal fascicle and inferior fronto-occipital fasciculus on the left side, as well as the capsula external and inferior fronto-occipital fasciculus on the right side, in patients after continuous TBS. In addition, compared to the sham group, patients stimulated with continuous TBS exhibited a dramatic increase in FA in the left external capsule. CONCLUSION: Our study presents strong evidence that rTMS significantly improves neurocognitive functions in USN, with continuous TBS showing the best curative effect. Enhanced connections in the white matter tract network related to visual attention, as assessed by DTI, might be the potential mechanism for the observed recovery in USN using continuous TBS. PMID- 26671119 TI - Does Parkinson's disease lead to alterations in the facial expression of pain? AB - Hypomimia which refers to a reduced degree in facial expressiveness is a common sign in Parkinson's disease (PD). The objective of our study was to investigate how hypomimia affects PD patients' facial expression of pain. The facial expressions of 23 idiopathic PD patients in the Off-phase (without dopaminergic medication) and On-phase (after dopaminergic medication intake) and 23 matched controls in response to phasic heat-pain and a temporal summation procedure were recorded and analyzed for overall and specific alterations using the Facial Action Coding System (FACS). We found reduced overall facial activity in response to pain in PD patients in the Off which was less pronounced in the On. Especially the highly pain-relevant eye-narrowing occurred less frequently in PD patients than in controls in both phases while frequencies of other pain-relevant movements, like upper lip raise (in the On) and contraction of the eyebrows (in both phases), did not differ between groups. Moreover, opening of the mouth (which is often not considered as pain-relevant) was the most frequently displayed movement in PD patients, whereas eye-narrowing was the most frequent movement in controls. Not only overall quantitative changes in the degree of facial pain expressiveness occurred in PD patients but also qualitative changes were found. The latter refer to a strongly affected encoding of the sensory dimension of pain (eye-narrowing) while the encoding of the affective dimension of pain (contradiction of the eyebrows) was preserved. This imbalanced pain signal might affect pain communication and pain assessment. PMID- 26671120 TI - Retrospective analysis of parkinsonian patients exhibiting normal (123)I-MIBG cardiac uptake. AB - BACKGROUND: Although most patients with Parkinson's disease (PD) show decreased cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, some exhibit normal uptake. We evaluated the clinical characteristics of such patients. METHODS: We enrolled 154 non-demented patients showing parkinsonism with normal cardiac MIBG uptake and had been clinically followed up during 29.9 +/- 27.6 months. We defined the patients who did not fit the exclusion criteria for PD and demonstrated >= 30% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score after anti-Parkinson agent administration as probable PD. We compared clinical characteristics and the cardiac MIBG heart-to-mediastinum (H/M) ratio between the probable PD group (N=37) and other groups (N=117). RESULTS: The probable PD group showed significantly higher UPDRS motor scores and greater incidence of tremor/rigidity than those of other groups. In addition, they showed a significantly lower cardiac MIBG H/M ratio in the delayed phase (delayed, p<0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p<0.0001). Among 16 probable PD patients undergoing serial cardiac MIBG scintigraphy, the delayed phase cardiac MIBG H/M ratio showed a significant decrease and WR significantly increased during follow-up periods. CONCLUSIONS: An increase in WR and lower delayed phase cardiac MIBG uptake were found to be characteristics of such patients. PMID- 26671121 TI - Contralateral ictal electrographic involvement is associated with decreased memory performance in unilateral mesial temporal sclerosis. AB - PURPOSE: To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). METHODS: We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wada memory asymmetry>0, and Symmetrical or Reversed memory asymmetry (S-RA) when <= 0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30 min) recall (RAVLT 7), and recall after 7 days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. RESULTS: Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient=1.32, p=0.029, odds ratio 3.77; 95% CI 1.1-12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. CONCLUSION: In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing. PMID- 26671122 TI - A case of progressive frontal lobe syndrome in a sporadic form of Cerebral Amyloid Angiopathy: A singular overlap with fronto-temporal dementia? PMID- 26671123 TI - Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation. AB - We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis. PMID- 26671124 TI - Dysferlinopathy in Iran: Clinical and genetic report. AB - BACKGROUND: Dysferlinopathy is caused by a very wide range of autosomal recessively inherited mutations of the Dysferlin gene. It causes a spectrum of muscle diseases including limb-girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy (MM). We describe the clinical course and mutational analyses of 15 Iranian patients with dysferlinopathy from 9 different families. METHODS: Genomic DNA was extracted from peripheral blood and 55 exons and flanking intronic boundaries of the dysferlin gene (DYSF; NM_003494.2) were screened for mutations and analyzed. RESULTS: From 15 studied patients in 9 families, 5 patients were male. Seven families had consanguineous marriage. Median age of onset was 16.8; and the median age of diagnosis was 26.6. The onset was clearly distal in 7 patients, and proximal in 6 patients. Three patients had partial biceps atrophy and 13 showed prominent calf muscle wasting. Foot plantar flexors, deep finger flexors and hip adductors were predominantly involved. Genetic testing showed homozygous mutation of dysferlin gene in 9 probands, 5 of which were not previously reported. CONCLUSION: This work, in fact, may help shed some light on the pattern of this morbidity in Iran, an effort that may have not been attempted so far. PMID- 26671125 TI - Pre-operative obesity may influence subthalamic stimulation outcome in Parkinson's disease. AB - BACKGROUND: Pre-operative predictive factors for optimal post-operative effect of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been previously reported. No study has explicitly assessed the link between excess pre operative body weight and STN stimulation outcome. METHODS: We retrospectively compared STN stimulation outcomes of 36 PD patients with excess pre-operative body weight (group 1) and 36 matched normal-weight pre-operative (group 2) PD patients. We focused on the post-operative outcomes in the sub-group of 12 obese (group 3) PD patients. RESULTS: The post-operative motor improvement and the reduction of severity of levodopa-related complications were not statistically different between groups 1 and 2 (P>0.05). In the obese group (group 3), the axial sub-score significantly improved by 29.8% in the on-drug/on-stimulation conditions whereas the improvement was not significant in the off-drug/on stimulation condition (22.4%, P=0.20). The post-operative Mattis Dementia Rating Score was significantly reduced in group 1 and group 3. DISCUSSION: We considered that the post-operative axial impairment observed in the obese PD patients might be essentially consecutive to disease progression and/or post-operative DBS consequences, i.e. surgical procedure or electrical stimulation itself. Moreover, it could be argued that musculoskeletal disorders associated with obesity were responsible for the incomplete efficacy of STN stimulation on axial sub-scores, by increasing gait and balance impairment. CONCLUSION: Pre-operative obesity may be regarded as a predictive clinical factor of axial and cognitive impairment after STN-DBS. PMID- 26671126 TI - Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke? AB - Mutations in the gene encoding phosphodiesterase 4D (PDE4D) enzyme are associated with ischemic stroke; however the functional implications of such mutations are not well understood. PDE4D is part of a complex protein family modulating intracellular signalling by cyclic nucleotides. The PDE4 family includes subtypes A-D, all of which show unique intracellular, cellular and tissue distribution. PDE4D is the major subtype expressed in human atrial myocytes and involved in the pathophysiology of arrhythmias, such as atrial fibrillation. The PDE4D enzyme hydrolyses cyclic adenosine monophosphate (cAMP). Though diverging results are reported, several population based studies describe association of various PDE4D single nucleotide polymorphisms (SNP) with cardio-embolic stroke in particular. Functionally, a down regulation of PDE4D variants has been reported in stroke patients. The anti-inflammatory and vasodilator properties of PDE4 inhibitors make them suitable for treatment of stroke and cardiovascular disease. PDE4D has recently been suggested as factor in atrial fibrillation. This review summarizes the possible function of PDE4D in the brain, heart, and vasculature. Further, association of the described SNPs, in particular, with cardioembolic stroke, is reviewed. Current findings on the PDE4D mutations suggest functionality involves an increased cardiac risk factor as well as augmented risk of atrial fibrillation. PMID- 26671127 TI - A novel embolic middle cerebral artery occlusion model induced by thrombus formed in common carotid artery in rat. AB - Stroke is a major cause of death and disability worldwide. However, treatment options to date are very limited. To meet the need for validating the novel therapeutic approaches and understanding the physiopathology of the ischemic brain injury, experimental stroke models were critical for preclinical research. However, commonly used embolic stroke models are reluctant to mimic the clinical situation and not suitable for thrombolytic timing studies. In this paper, we established a standard method for producing a rat embolic stroke model with autologous thrombus formed within the common carotid artery (CCA) by constant galvanic stimulation. Then the thrombus was shattered and channeled into the origin of the MCA and small (lacunar) artery. To identify the success of MCA occlusion, regional cerebral blood flow was monitored, neurological deficits and infarct volumes were measured at 2, 4 and 6h postischemia. This model developed a predictable infarct volume (38.37 +/- 2.88%) and gradually reduced blood flow (20% of preischemic baselines) within the middle cerebral artery (MCA) territory. The thrombus occluded in the MCA was able to be lysed by a tissue-type plasminogen activator (t-PA) within 4h postischemia. The techniques presented in this paper would help investigators to overcome technical problems for stroke research. PMID- 26671128 TI - Correlation of mechanical impact responses and biomarker levels: A new model for biomarker evaluation in TBI. AB - A modified Marmarou impact acceleration model was used to help screen biomarkers to assess brain injury severity. Anesthetized male Sprague-Dawley rats were subjected to a closed head injury from 1.25, 1.75 and 2.25 m drop heights. Linear and angular responses of the head were measured in vivo. 24h after impact, cerebrospinal fluid (CSF) and serum were collected. CSF and serum levels of phosphorylated neurofilament heavy (pNF-H), glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), and amyloid beta (Abeta) 1-42 were assessed by enzyme-linked immunosorbent assay (ELISA). Compared to controls, significantly higher CSF and serum pNF-H levels were observed in all impact groups, except between 1.25 m and control in serum. Furthermore, CSF and serum pNF-H levels were significantly different between the impact groups. For GFAP, both CSF and serum levels were significantly higher at 2.25 m compared to 1.75 m, 1.25 m and controls. There was no significant difference in CSF and serum GFAP levels between 1.75 m and 1.25 m, although both groups were significantly higher than control. TBI rats also showed significantly higher levels of IL-6 versus control in both CSF and serum, but no significant difference was observed between each impact group. Levels of Abeta were not significantly different between groups. Pearson's correlation analysis showed pNF-H and GFAP levels in CSF and serum had positive correlation with power (rate of impact energy), followed by average linear acceleration and surface righting (p<0.01), which were good predictors for traumatic axonal injury according to histologic assessment in our previous study, suggesting that they are directly related to the injury mechanism. The model used in this study showed a unique ability in elucidating the relationship between biomarker levels and severity of the mechanical trauma to the brain. PMID- 26671129 TI - Impact of BNP on cryptogenic stroke without potential embolic sources on transesophageal echocardiography. AB - BACKGROUND: Clinical characteristics are important for determining the etiologies of embolic stroke, including patent foramen ovale and complex aortic plaques demonstrated on transesophageal echocardiography (TEE). This study sought to analyze the clinical signs of cryptogenic stroke (CS) without such embolic etiologies and to examine the association between CS and brain natriuretic peptide (BNP), which is currently unknown. METHODS: Patients with CS after routine examinations who underwent TEE were included in this single-center observational study. Patients were classified into the potential embolic sources (PES) group (patients having PES on TEE) and the no potential embolic source (NPES) group. Patients were also categorized according to the tertile of BNP. RESULTS: A total of 158 patients (age, 64.0 +/- 13.9 years; 119 males) with CS were enrolled. The PES group had 108 (68%) patients, and the NPES group had 50 (32%). Hypertension was more common, and glucose, D-dimer, and BNP were higher in the NPES than in the PES group (p<0.05). NPES was independently associated with high-BNP tertile (OR: 5.61; 95% CI: 1.91 to 16.44; p=0.002). CONCLUSIONS: BNP, an indicator of cardioembolism, was closely associated with NPES. Cardiogenic mechanisms may be implicated in the etiology of CS without potential embolic etiologies on TEE. PMID- 26671130 TI - The etiologic subtype of intracerebral hemorrhage may influence the risk of significant hematoma expansion. AB - BACKGROUND: Intracerebral hemorrhage (ICH) growth is an important independent predictor of clinical deterioration and outcome. Little is known about the association between etiology of ICH and occurrence of hematoma expansion (HE). The aim of the present study was to assess whether ICH etiologic subtype may influence the risk of significant HE. METHODS: We conducted an analysis on retrospectively collected data of 424 consecutive patients with ICH, who were admitted to the Verona General Hospital, from March 2011 to December 2014. Using the SMASH-U (Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined) classification, we identified the ICH etiologic subtypes. Outcome measure was significant HE (an absolute increase in ICH volume>12.5 mL or >50%) within 48 h. RESULTS: Significant HE occurred in 11/57 (19.3%) Amyloid, 7/14 (50%) Structural, 31/57 (54.4%) Medication, 25/44 (56.8%) in Systemic, 62/139 (44.6%) Hypertensive, and 21/68 (30.9%) Undetermined ICH. Baseline ICH volume (OR 1.011 per mL, 95% CI 1.006 1.017, p<0.001) and onset-to-baseline CT time (OR 0.919 per hour, 95% CI 0.852 0.990, p=0.027) were predictors of significant HE. Compared with Amyloid ICH, ORs for significant HE were higher in patients with Structural ICH (OR 1.430, 95% CI 1.060-1.948, p=0.023), Medication ICH (OR 4.344, 95% CI 1.382-13.653, p=0.012), Systemic ICH (OR 1.796, 95% CI 1.070-3.015, p=0.027), and Hypertensive ICH (OR 3.081, 95% CI 1.426-6.655, p=0.004). CONCLUSION: Our study shows that Structural, Medication, Systemic, and Hypertensive ICH were the etiologic subtypes associated with a higher risk of significant HE, compared with Amyloid ICH patients. PMID- 26671131 TI - Serum caspase-cleaved cytokeratin-18 levels and outcomes after aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE: Cell apoptosis is involved in acute brain injury after aneurysmal subarachnoid hemorrhage (aSAH). The protein cytokeratin-18 (CK-18) is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Our study examined the relationship between circulating CCCK-18 levels and long-term clinical outcomes among aSAH patients. METHODS: We recruited 128 aSAH patients and 128 controls (matched on age and sex). Serum was collected at admission to the emergency department. Unfavorable outcome was defined as the Glasgow Outcome Score scores of 1-3. After a 6-month follow-up period, outcomes were assessed using a logistic regression analyses. The prognostic predictive values were evaluated according to receiver operating curves analysis. RESULTS: aSAH patients had higher plasma CCCK 18 levels compared to controls (235.1 +/- 86.8 U/L vs. 25.6 +/- 23.4 U/L, P<0.001). CCCK-18 was independently associated with World Federation of Neurological Surgeons (WFNS) scores (t=4.460, P<0.001) and modified Fisher scores (t=3.781, P<0.001). Furthermore, CCCK-18 levels were markedly higher among patients with an unfavorable outcome and among non-survivors. CCCK-18 was yet identified as an independent prognostic predictor for mortality (odds ratio, 5.769; 95% confidence interval, 1.196-27.832; P=0.029) and unfavorable outcome (odds ratio, 4.909; 95% confidence interval, 1.521-15.838; P=0.008), as well as had similar predictive values for them compared with WFNS scores and modified Fisher scores. CONCLUSIONS: High circulating CCCK-18 levels were associated with injury severity and a poor clinical outcome after aSAH and CCCK-18 had the potential to be a good prognostic biomarker for aSAH. PMID- 26671132 TI - Retinal nerve fiber layer thickness and neurologic disability in relapsing remitting multiple sclerosis. AB - OBJECTIVE: To assess the correlation between disability progression assessed by expanded disability status scale (EDSS) and peripapillary retinal nerve fiber layer thickness (RNFLT), macular thickness and macular volume obtained by spectral domain OCT (SDOCT) in patient with relapsing-remitting multiple sclerosis. METHODS: We conducted a cross sectional study by recruiting 104 with relapsing-remitting MS patients and 51 healthy controls. Patients' clinical characteristics and neurologic disability was recorded from the subject clinical records. All patients had complete neuro-ophthalmic and neurological assessments. SDOCT performed to obtain peripapillary RNFLT, macular thickness and volume. RESULTS: There was a statistically significant correlation between the mean EDSS scores and the average RNFLT (p = 0 .006; r = - 0.268) along with superior (p = 0.020; r = - 0.228), inferior (p = 0.007; r = - 0.262) and temporal (p = 0.031; r = - 0.212) quadrants. However, macular thickness (p = 0.205; r = - 0.125) and volume (p = 0.178; r = - 0.133) were not significantly correlated with EDSS scores. CONCLUSION: Our study showed a significant correlation between RNFLT and disability progression assessed by mean of EDSS in patients with relapsing remitting MS. RNFLT can be a useful tool to estimate neurological disability in newly diagnosed patients or patients with early RRMS. PMID- 26671133 TI - Clinical characteristics of idiopathic normal pressure hydrocephalus with Lewy body diseases. AB - BACKGROUND: Comorbidity of idiopathic normal pressure hydrocephalus and neurodegenerative diseases presents a diagnostic challenge. The aim of this study was to elucidate the clinical features of iNPH patients who are possibly comorbid with Lewy body diseases. METHODS: In this study, we retrospectively analyzed the records of consecutive 127 patients with definite idiopathic normal pressure hydrocephalus. (123)I-Metaiodobenzylguanidine myocardial scintigraphy was undertaken to 21 patients with idiopathic normal pressure hydrocephalus because of suspicion for comorbid Lewy body diseases. RESULTS: As a result, 7 of the 21 patients with idiopathic normal pressure hydrocephalus exhibited cardiac sympathetic abnormality. Idiopathic normal pressure hydrocephalus patients with cardiac sympathetic dysfunction had the constellation of clinical findings, such as younger onset, less severe urinary dysfunction, kinesie paradoxale, and cogwheel rigidity. CONCLUSIONS: Our results suggested that comorbidity of idiopathic normal pressure hydrocephalus and Lewy body diseases are not rare condition and careful screening for potentially-curative surgery is important especially in atypical cases. PMID- 26671134 TI - Male sexual function in presymptomatic gene carriers and patients with Huntington's disease. AB - AIMS: To report sexual dysfunction in a systematically studied cohort of men with Huntington's disease (HD), and compare them with control men of a similar age. METHODS: In men with HD and asymptomatic HD gene carriers, the male sexual dysfunction questionnaire (International Index of Erectile Function--IIEF, covering erectile and orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction), neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC) Score were utilized. RESULTS: Responses were obtained from 23 HD patients and 2 HD gene carriers. HD patients reported more problems with erection, intercourse satisfaction and overall satisfaction (p<0.05) compared to 41 controls. HD patients generally reported reduced sexual desire and performance. Sexual dysfunction progressed in parallel with patients' decline in motor (UHDRS) and TFC, but was not related to patients' age and duration of disease. CONCLUSIONS: Our study demonstrated a significant impact of HD on male sexual function that progressed in parallel with motor and total patient (TFC) dysfunction. Physicians helping HD patients should also consider this largely neglected aspect of the disease. PMID- 26671135 TI - Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug. AB - OBJECTIVE: This study aimed to determine the risk factors for recurrent post stroke seizure (PSS) and the efficacy of anti-epileptic drugs (AED) in patients having intracerebral hemorrhage (ICH) with initial seizure. METHODS/SUBJECTS: A total of 1920 consecutive patients with ICH from 2004 to 2012 were investigated retrospectively. The relationships among the baseline clinical and radiological data, administration of AED, and incidence of initial and recurrent PSS were evaluated using multiple logistic regression analysis. RESULTS: Seizures occurred in 127 (6.6%) of the 1920 patients, displaying statistically significant relationships with cortical involvement of a cerebral lesion (P<0.001), non hypertensive ICH (P<0.001), younger age (P<0.001), and severe neurological deficits (P<0.001). Early (4.3%) and late seizure (2.3%) had no significant relationship with the development of recurrent PSS. Larger volume of hematoma was the only independent factor associated with recurrence of PSS (OR 1.03; 95% CI 1.00-1.05; P=0.027). A Kaplan Meier survival analysis revealed that AED treatment had a poor association with recurrence of PSS (P=0.750). CONCLUSIONS: Larger volume of hematoma was predictive of recurrence of PSS. AED therapy had poor association with preventing the recurrence of PSS. PMID- 26671136 TI - Cognitive impairment of Japanese multiple sclerosis patients: Follow-up study using BRB-N assessment tool. AB - OBJECTIVES: The purpose of this study was to evaluate cognitive function in patients with multiple sclerosis (MS), compared with control subjects, and to establish whether decline of cognitive function continues in the patients during remission. METHODS: The Japanese version of the Brief Repeatable Battery of Neuropsychological tests (BRB-N), which includes the selective reminding test (SRT), spatial recall test (SPART), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), and the word list generation test (WLG), was performed in 34 Japanese patients with MS (8 males, 26 females; mean age, 42 years) and in 37 age- and education-matched healthy controls (20 males, 17 females; mean age, 36 years). BRB-N was conducted at intervals of two years for MS patients who remained in remission, and the cognitive changes were evaluated by comparing the results with those of the initial examination at entry into the study. RESULTS: The MS patients showed lower BRB-N scores than controls, with high significance in the SRT, SRT-D, SDMT and PASAT tests (p<0.01). The BRB-N scores of the MS patients who remained in remission were not significantly changed for at least 2 years. CONCLUSIONS: The Japanese version of the BRB-N is useful to clarify the nature of cognitive impairment in Japanese MS patients. Based on this neuropsychological assessment, we suggest that working memory and information-processing speed are key deficits. Patients who remained in remission showed little or no further impairment of cognitive functions for at least two years. PMID- 26671137 TI - Brachial-ankle pulse wave velocity and ankle-brachial index are complementary tools for transcranial Doppler ultrasonography in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke. AB - The aim of this study was to explore whether brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are suitable to serve as complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke (AIS). A total of 52 patients with AIS onset and 52 age-matched healthy controls were included in this study. All participants received TCD detection, and baPWV and ABI were measured. Computed topography (CT)/magnetic resonance imaging (MRI) was applied to confirm diagnosis. TCD data from all participants was collected and reviewed to diagnose stenosis and occlusion of the major intracranial arteries. Receiver operating characteristic (ROC) analysis and logistic regression analysis were used to assess and compare the diagnostic accuracy of the various diagnostic approaches. We found that a combination of TCD with either baPWV or ABI, or a combination of the three provided a significantly higher area under the curve (AUC) in detecting stenosis or occlusion in various intracranial arteries, excluding the anterior cerebral artery (ACA), when compared to TCD alone, thereby demonstrating that these combined approaches provide improved diagnostic accuracy. In conclusion, our findings suggest that both baPWV and ABI are suitable complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in AIS patients and that these combinations may assist in facilitating the diagnostic process associated with this disease. PMID- 26671138 TI - Association of HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes with myasthenia gravis and its subgroups in the Iranian population. AB - Heterogenic pattern of HLA associations with myasthenia gravis (MG) among different ethnicities and also among different MG subgroups has been the subject of debate in large series of many studies. One hundred and sixty Iranian MG patients were investigated for HLA class II (DRB1, DQA1, DQB1) associations compared to two hundred healthy controls from the same ethnic population. DRB1*11 DQA1*0501 DQB1*0301 haplotype was found to be protective for total (ocular plus generalized) MG (Pc=0.005, OR=0.49) and generalized MG (Pc=0.008, OR=0.49). DRB1*04 DQA1*0301 DQB1*0302 haplotype (Pc=0.03, OR=2.25) was predisposing for anti-acetylcholine receptor (AChR) antibody-positive MG, while DRB1*16 DQA1*0102 DQB1*05 (Pc=0.013, OR=4.28) was predisposing for anti-muscle specific tyrosine kinase (MuSK) antibody-positive MG. There was also a trend of positive association for DRB1*14 DQA1*0104 DQB1*05 haplotype with MuSK-positive MG (Pc=0.054, OR=3.97). Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG. This study highlights the importance of appropriate MG subgrouping according to clinical and paraclinical characteristics in HLA studies among MG patients. PMID- 26671139 TI - Neuroimaging findings and follow-up in two cases of severe ethylene glycol intoxication with full recovery. PMID- 26671140 TI - Intracranial arterial disease in CADASIL patients. AB - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the involvement of cerebral small arteries. Although cerebral large artery disease has been reported in CADASIL patients, the prevalence and location of relevant cerebral arterial disease have not been elucidated. In this study, we aim to characterize infarctions associated with cerebral large artery disease in CADASIL patients. METHODS: We retrospectively reviewed 49 consecutive symptomatic patients with genetically confirmed CADASIL, who visited the Asan Medical Center between December 2002 and December 2013. Infarctions located within the territory of a relevant, large cerebral artery were identified with the use of magnetic resonance imaging and magnetic resonance angiography. Patients with or without territorial patterns associated with large artery disease were compared. RESULTS: Out of a total of 49 patients, 23 patients had cerebral infarction. Among these, seven had infarction associated with cerebral large artery disease. The corresponding vascular lesions were located in the intracranial arteries in all seven patients. There were no differences between patients with or without territorial infarction in terms of vascular risk factors, microbleeds, white matter changes, or mutations involving cysteine. A literature review illustrates that symptomatic intracranial diseases are present in CADASIL patients at least in East Asia. CONCLUSION: Infarction in association with intracranial arterial disease may be a manifestation of CADASIL. Further studies are needed to elucidate the pathologic characteristics and to see whether this occurs exclusively in East Asia. PMID- 26671141 TI - Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29. AB - Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus. PMID- 26671142 TI - Reduction of glutamate-induced excitotoxicity in murine primary neurons involving calpain inhibition. AB - Excessive glutamate secretion leads to excitotoxicity, which has been shown to underlie neurodegenerative disorders. Excitotoxicity is in part exerted by overactivation of calpains, which promote neuronal cell death via induction of limited proteolysis of the cellular proteins p35, regulatory subunit of cyclin dependent kinase 5, and alphaII-spectrin. We used primary murine neuronal cells in a model of glutamate toxicity. The protease inhibitor alpha1-antitrypsin was able to prevent glutamate toxicity as determined by MTT assay and immunofluorescence. Calpain and caspase 3 activity were reduced following alpha1 antitrypsin treatment, as assessed by calpain and caspase 3 activity assays. In addition we could observe a modulation of cleavage of the calpain/caspase substrates alphaII-spectrin and p35 in Western blots. In summary, alpha1 antitrypsin shows inhibitory effects on excitotoxicity of primary neurons involving the inhibition of calpain activity. The advantage of using alpha1 antitrypsin is that the substance is already in clinical use for the treatment of patients with hereditary alpha1-antitrypsin deficiency. Further experiments are required in animal models of neurodegenerative disorders to assess the suitability of this substance in patients suffering from Alzheimer's disease or Parkinson's disease. PMID- 26671143 TI - Association of serum uric acid level with cognitive function among patients with multiple system atrophy. AB - BACKGROUND AND OBJECTIVE: Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA) and cognitive impairment. Uric acid has an anti oxidative effect. Our objective is to clarify the correlations between serum uric acid and cognitive function as well as frontal lobe function in Chinese MSA patients. METHODS: All of MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Unified MSA Rating Scale (UMSARS). The fasting serum uric acid concentrations of MSA patients were measured. RESULTS: A total of 89 probable MSA patients with a mean age of 58.6 +/- 10.0 years old and disease duration of 2.6 +/- 1.5 years were included. Thirty-three patients (37.1%) had global cognitive deficits according to ACE-R. Based on FAB, 35 patients (39.3%) had frontal lobe dysfunction. After adjusting for educational years, patients with cognitive deficits had lower uric acid level than patients without cognitive deficits. Patients with frontal lobe dysfunction had lower uric acid level after adjusting for UMSARS scores. In a forward multiple linear regression, uric acid level and educational years were the variables predicting the ACE-R score (F=36.540, R(2)=0.459, p=0.0001), uric acid accounting for 14% of the total variables. Uric acid was the only variable contributing to the FAB score (F=18.551, R(2)=0.176, p=0.0001). CONCLUSION: Our study suggested that low level of serum uric acid was associated with cognitive deficits in MSA. Low uric acid level predicting cognitive decline in MSA needs more studies. PMID- 26671144 TI - Quantitative assessment of cerebral gray matter density change in progressive supranuclear palsy using voxel based morphometry analysis and cerebral MR T1 weighted FLAIR imaging. AB - PURPOSE: To investigate the gray matter (GM) atrophy in Progressive supranuclear palsy (PSP) using T1-weighted Fluid-Attenuated Inversion Recovery (FLAIR) images based on voxel based morphometry (VBM) method. MATERIALS AND METHODS: In this study, we firstly modified the conventional VBM method to make it can process the T1-weighted FLAIR brain images. Then, we used this method on the 24 PSP patients and 23 healthy age- and sex-matched control subjects to find the local gray matter density changes of PSP patients. RESULTS: Compared with healthy controls, GM reductions of PSP patients mainly located in the thalamus, basal ganglia, pons, midbrain, insular cortex, frontal cortex, temporal lobe, cerebellum, cingulate cortex and hippocampus. CONCLUSION: We used the modified VBM technique into T1 FLAIR data to study the brain gray matter atrophy in PSP, and found some new atrophy areas, including pallidum, middle and posterior cingulum, lingual, fusiform gyrus and the post part of inferior temporal gyrus. These areas have not been described in the former VBM studies, but they revealed abnormity in the pathologic and other studies on PSP. Our results might be expected to provide significant underlining neurology information and diagnostic value for PSP. PMID- 26671145 TI - Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia. AB - Atomoxetine (ATX) is a non-stimulant selective norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). In this study, we firstly examined neuroprotective effects of pre- or post-treatment with 15 and 30 mg/kg ATX against ischemic damage in the gerbil hippocampal cornus ammonis 1 (CA1) region subjected to 5 min of transient cerebral ischemia using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-J B histofluorescence staining. We found that only pre-treatment with 30 mg/kg ATX protected CA1 pyramidal neurons from ischemic insult. In addition, pre-treatment with 30 mg/kg ATX, which had neuroprotective effect against ischemic damage, distinctly attenuated the activation of astrocytes and microglia in the ischemic CA1 region compared with the vehicle-treated ischemia group by glial fibrillary acidic protein (for astrocytes) and ionized calcium-binding adapter molecule 1 (for microglia) immunohistochemistry. In brief, our present results indicate that ATX has neuroprotective effect against transient cerebral ischemic insult and that the neuroprotective effect of ATX may be closely associated with attenuated glial activation. PMID- 26671146 TI - Long term outcome and predictors of ischemic stroke recurrence in adult moyamoya disease. AB - OBJECTIVE: We sought to identify the clinical outcome and predictors for ischemic stroke recurrence in adults with symptomatic moyamoya disease (MMD). METHODS: We analyzed 104 adult MMD patients with ischemic stroke or TIA registered at our institution. All patients underwent digital subtraction angiography and single photon emission computed tomography to measure disease severity and cerebral vascular reserve (CVR). A Cox regression model was used to identify predictors of recurrent ischemic stroke. RESULTS: Fifty-nine patients were non-surgically treated and 45 patients were surgically treated. In the non-surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 1.6% in the first year and 11.8% in the 5th year. Hypertension (hazard ratio [HR]=0.07, 95% confidence interval [CI] 0.01-0.99), diabetes (HR=35.16, 95% CI 2.61-474.16), presence of steno-occlusive lesion in posterior cerebral arteries (HR=17.53, 95% CI 2.02 152.43), and extended or global decreased CVR (HR=13.62, 95% CI 1.55-119.84) were independent predictors of recurrence. In the surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 24.4% in the first year and 24.4% in the 5th year. Half of the recurred patients experienced recurrent ischemic strokes postoperatively. Diabetes was the only predictor of recurrent ischemic stroke (HR=6.17, 95% CI 1.31-29.14). CONCLUSIONS: In non-surgically treated MMD, PCA stenosis and CVR were identified as predictors of ischemic stroke recurrence. Diabetes was an independent predictor of recurrent ischemic stroke in both non surgical and surgically treated MMD groups. PMID- 26671147 TI - Mouth cancer in inflammatory bowel diseases. AB - Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic. PMID- 26671148 TI - Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism. AB - A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to beta-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. PMID- 26671149 TI - Depletion of H2S during obesity enhances store-operated Ca2+ entry in adipose tissue macrophages to increase cytokine production. AB - The increased production of proinflammatory cytokines by adipose tissue macrophages (ATMs) contributes to chronic, low-level inflammation during obesity. We found that obesity in mice reduced the bioavailability of the gaseous signaling molecule hydrogen sulfide (H2S). Steady-state, intracellular concentrations of H2S were lower in ATMs isolated from mice with diet-induced obesity than in ATMs from lean mice. In addition, the intracellular concentration of H2S in the macrophage cell line RAW264.7 was reduced during an acute inflammatory response evoked by the microbial product lipopolysaccharide (LPS). Reduced intracellular concentrations of H2S led to increased Ca(2+) influx through the store-operated Ca(2+) entry (SOCE) pathway, which was prevented by the exogenous H2S donor GYY4137. Furthermore, GYY4137 inhibited the Orai3 channel, a key component of the SOCE machinery. The enhanced production of proinflammatory cytokines by RAW264.7 cells and ATMs from obese mice was reduced by exogenous H2S or by inhibition of SOCE. Together, these data suggest that the depletion of macrophage H2S that occurs during acute (LPS-induced) or chronic (obesity) inflammation increases SOCE through disinhibition of Orai3 and promotes the production of proinflammatory cytokines. PMID- 26671151 TI - White matter integrity and cognitive dysfunction: Radiological and neuropsychological correlations. AB - Cerebral white matter (WM) is comprised of nerve fibers interconnecting neurons in the cerebral cortex or the deep structures. With advancing age, WM frequently shows hyperintense lesions in T2-weighted or fluid-attenuated inversion recovery images in both the periventricular and deep WM. Patients with these WM lesions might manifest a variety of symptoms, such as parkinsonism, cognitive impairment, depression and apathy, when these WM lesions become sufficiently confluent and diffuse. However, there are inconsistencies with respect to their clinical significance, because patients with extensive WM lesions might remain asymptomatic. The present review focuses on the pathological mechanism underlying why the loss of integrity of nerve fibers in the WM induces neuropsychological symptoms. PMID- 26671150 TI - Network-level effects of kinase inhibitors modulate TNF-alpha-induced apoptosis in the intestinal epithelium. AB - Individual signaling pathways operate in the context of the broader signaling network. Thus, the response of a cell to signals from the environment is affected by the state of the signaling network, such as the clinically relevant example of whether some components in the network are inhibited. The cytokine tumor necrosis factor-alpha (TNF-alpha) promotes opposing cellular behaviors under different conditions; the outcome is influenced by the state of the network. For example, in the mouse intestinal epithelium, inhibition of the mitogen-activated protein kinase (MAPK) kinase MEK alters the timing of TNF-alpha-induced apoptosis. We investigated whether MAPK signaling directly influences TNF-alpha-induced apoptosis or whether network-level effects secondary to inhibition of the MAPK pathway alter the cellular response. We found that inhibitors of the MAPK kinase kinase Raf, MEK, or extracellular signal-regulated kinase (ERK) exerted distinct effects on the timing and magnitude of TNF-alpha-induced apoptosis in the mouse intestine. Furthermore, even different MEK inhibitors exerted distinct effects; one, CH5126766, potentiated TNF-alpha-induced apoptosis, and the others reduced cell death. Computational modeling and experimental perturbation identified the kinase Akt as the primary signaling node that enhanced apoptosis in the context of TNF-alpha signaling in the presence of CH5126766. Our work emphasizes the importance of integrated network signaling in specifying cellular behavior in response to experimental or therapeutic manipulation. More broadly, this study highlighted the importance of considering the network-level effects of pathway inhibitors and showed the distinct effects of inhibitors that share the same target. PMID- 26671152 TI - Impact of cerebral white matter changes on functionality in older adults: An overview of the LADIS Study results and future directions. AB - The evidence on the clinical significance of cerebral white matter changes (WMC) has mounted over the past few decades. WMC are recognized as one of the neuroimaging features of cerebral small vessel disease, and are associated with various disturbances and a poor prognosis. The Leukoaraiosis and Disability (LADIS) Study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration aimed at assessing the role of WMC as an independent predictor of the transition to disability in initially non-disabled patients aged 65-84 years. Besides the demonstration that severe WMC cause a more than double risk of transition from an autonomous to a dependent status after 3 years of follow-up, the LADIS Study has also provided evidence on the role of WMC in relation to the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, the presence of urinary disturbances, and various neurological abnormalities. The possible role of other lesions (lacunar infarcts, cerebral atrophy, corpus callosum morphology) and microstructural abnormalities (diffusion-weighted imaging changes in normal appearing brain tissue and in WMC) has also been investigated. In the present article, we review the main results of the LADIS Study and offer some considerations for future developments in the field, paying attention to the potential use of WMC progression as a surrogate marker in intervention trials in cerebral small vessel diseases. We also discuss some therapeutic perspectives regarding the beneficial impact of physical activity on the risk of vascular cognitive impairment in patients with WMC. PMID- 26671153 TI - White matter hyperintensities and geriatric syndrome: An important role of arterial stiffness. AB - White matter hyperintensities (WMH) are defined as cerebral white matter changes presumed to be of vascular origin, bilateral and mostly symmetrical. They can appear as hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, and as isointense or hypointense on T1-weighted magnetic resonance imaging of the brain. WMH have been focused on because of their clinical importance as a risk factor for cerebrovascular diseases and cognitive impairment. WMH are associated with geriatric syndrome, which is defined by clinical symptoms characteristic of older adults, including cognitive and functional impairment and falls. Cerebral small vessel diseases, such as WMH, might play an important role as risk factors for cerebrovascular diseases, cognitive impairment and geriatric syndrome through the mechanism of arterial stiffness. However, the vascular, physiological and metabolic roles of arterial stiffness remain unclear. Basically, arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. These changes might arise from hemodynamic stress as a result of a "tsunami effect" on cerebral parenchyma. In the present article, we review the clinical characteristics of WMH, focusing particularly on two associations: (i) those between cerebral small vessel diseases including WMH and arterial stiffness; and (ii) those between WMH and geriatric syndrome. PMID- 26671154 TI - Visit-to-visit blood pressure variability and dementia. AB - Visit-to-visit blood pressure variability has been shown to be an independent risk factor for stroke and cognitive impairment. However, the underlying mechanisms are not fully understood. Artery remodeling and silent cerebral injury are suggested to be involved in the relationship between visit-to-visit blood pressure variability and cognitive impairment. The present review article summarizes the recent literature on these topics. Here we review visit-to-visit blood pressure variability, artery remodeling, silent cerebral injury and an issue regarding the impact of these components on dementia including Alzheimer's disease. PMID- 26671155 TI - Diabetes mellitus and white matter hyperintensity. AB - White matter hyperintensity (WMH) is a brain lesion detected as a high-intensity area in magnetic resonance imaging T2 and fluid-attenuated inversion recovery images, and it has been suggested that WMH reflects damage to small vessels in periventricular and subcortical areas. Although WMH has been linked to the incidence of stroke, more recently it has been clarified that WMH is also associated with progression of cognitive decline and functional disability, which are components of so-called geriatric syndrome. In addition to hypertension, which is the classical risk factor for WMH, evidence has been accumulating to suggest that diabetes mellitus could also be associated with WMH progression, and some studies have shown that WMH severity is correlated with cognitive decline in patients with diabetes. The factors that accelerate WMH formation in elderly patients with diabetes remain poorly defined. It is considered that insulin resistance is an exacerbating factor, but the effects of hypertension, dyslipidemia or other vascular risk factors have yet be clarified, and further studies are required. PMID- 26671156 TI - Volumetric analyses of cerebral white matter hyperintensity lesions on magnetic resonance imaging in a Japanese population undergoing medical check-up. AB - AIM: To clarify growth patterns, spatial distribution and risk factors of cerebral white matter hyperintensity (WMH) lesions on magnetic resonance imaging. METHODS: We analyzed volumes of cerebral WMH lesions in those who underwent brain magnetic resonance imaging as a hospital-based health check-up in 2012 and 2013 by using a computational quantitative image analysis software (Software for NeuroImage Processing in Experimental Research). After excluding subjects not suitable for volumetric analyses because of pathological brain conditions, a total of 1047 healthy participants (mean age 56.6 years) were included for the analyses. First, the relationship of computational volumetry and conventional qualitative visual evaluation by Shinohara grading was evaluated. Volumes of WMH lesions were analyzed according to age and the different cerebral lobes. Finally, clinical risk factors associated with WMH lesions were assessed. RESULTS: Volumes of WMH lesions were significantly correlated with Shinohara grading (P < 0.001). WMH lesions significantly enlarged with aging (P < 0.001) except for the occipital lobe, especially in participants aged 50 years or older. Age and systolic blood pressure were significantly related to volumes of WMH lesions in all the lobes, whereas diastolic blood pressure was not related only in the occipital lobe. CONCLUSION: Based on computational quantitative volumetric analyses, cerebral WMH lesions increased with age, and were associated with blood pressure. However, the occipital lobe was the only exception to these findings. PMID- 26671157 TI - Correlation between the serum eicosapentanoic acid-to-arachidonic acid ratio and the severity of cerebral white matter hyperintensities in older adults with memory disorder. AB - AIM: The relationships of n-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid (EPA), to stroke and cardiovascular events have been studied extensively. The present study was undertaken to analyze the relationships of the severity of cerebral white matter hyperintensities (WMH) to the blood polyunsaturated fatty acids level and the ratio of serum EPA level to the serum arachidonic acid (AA) level (EPA/AA ratio) among older adults. METHODS: A total of 150 patients underwent diagnostic magnetic resonance imaging and blood sampling under the fasting state. In regard to WMH, the periventricular hyperintensities and deep white matter hyperintensities were rated according to the Fazekas classification. The serum docosahexaenoic acid, EPA, AA, dihomo-gamma-linolenic acid and EPA/AA ratio were compared in relation to the grade of severity of WMH. Furthermore, multiple regression analysis was carried out with age, sex and atherosclerosis risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking status) as the covariables, serum polyunsaturated fatty acids level as an independent variable and Fazekas grade as the dependent variable. RESULTS: A rise of the periventricular hyperintensities grade was associated with a significant reduction of the mean EPA level (P < 0.05) and EPA/AA ratio (P < 0.05). The multiple regression analysis identified a significant negative correlation between the periventricular hyperintensities grade and the serum EPA/AA ratio (beta = -0.215, P < 0.05). CONCLUSION: These results suggest that the serum EPA/AA ratio have an important role in the formation and progression of WMH. PMID- 26671158 TI - Differences in peripheral oxidative stress markers in Alzheimer's disease, vascular dementia and mixed dementia patients. AB - AIMS: We determined whether the possible roles of oxidative stress differ in the pathophysiology and cognitive decline of Alzheimer's disease (AD), vascular dementia (VaD) and mixed Alzheimer's/vascular dementia (MD). METHODS: We measured the levels of diacron reactive oxygen metabolite (dROM), reflecting the amount of organic hydroperoxides, and biological anti-oxidant potential (BAP), measuring the ferric reducing ability of blood plasma, in 72 patients with AD, 27 with VaD, 24 with MD and 53 non-demented outpatients (control group). In addition, endogenous plasma anti-oxidants, such as albumin, total bilirubin and uric acid, were compared among the groups. All participants with VaD and MD showed extensive white matter hyperintensity, in addition to multiple lacunes. RESULTS: The dROM levels were significantly higher in the AD and MD groups than in the control group. The BAP levels were significantly lower in the MD group than in the control, AD and VaD groups. The AD group showed significantly lower levels of bilirubin and uric acid than the control group. The MD group showed a significantly lower level of albumin than the control and AD groups, and a significantly lower level of bilirubin than the control group. The Mini-Mental State examination scores correlated significantly with dROM levels and BAP/dROM ratios in the AD group. CONCLUSIONS: An imbalance in pro-oxidant and anti-oxidant defenses is apparently involved in the pathophysiology of the AD and MD groups. The extent of oxidative stress damage might differ in subtypes of dementia by being greater in the MD group than in other types of dementia. Synergic effects of the degenerative element of AD and white matter lesions might be associated with oxidative stress damage in the MD group. PMID- 26671160 TI - Severity of white matter hyperintensities in older adults aged in their mid 80s and its relationship with hemodynamic and cardiac parameters. AB - AIM: In the present study, we analyzed the severity of white matter hyperintensities detected on magnetic resonance imaging of the brain in older Japanese adults who were aged in their mid 80s, and examined its relationships with the clinical parameters. METHODS: To identify factors related to the severity of white matter hyperintensities in 33 older adult attendees of our outpatient clinic and 17 older adults living in a group home, we carried out logistic regression analyses and/or correlation analyses. RESULTS: Cognitive function and activities of daily living were significantly correlated with the severity of white matter hyperintensities. Multivariate analysis identified activities of daily living, but not cognitive function, as being independently associated with the severity of white matter hyperintensities. Several hemodynamic and cardiac parameters, including diastolic blood pressure, hemoglobin, serum level of N-terminal pro-brain natriuretic peptide, cardiothoracic ratio on the chest X-ray, severity of supraventricular arrhythmias on a Holter electrocardiogram and serum levels of docosahexaenoic acid, were significantly correlated with the severity of white matter hyperintensities. In contrast, the serum cholesterol, glycosylated hemoglobin value and systolic blood pressure were not correlated with the severity of white matter hyperintensities. CONCLUSIONS: The severity of white matter hyperintensities detected on magnetic resonance imaging of the brain in older Japanese patients aged in their mid 80s was significantly correlated with activities of daily living, hemodynamic and cardiac parameters, and the serum level of docosahexaenoic acid. PMID- 26671159 TI - Impact of night-time blood pressure on cerebral white matter hyperintensity in elderly hypertensive patients. AB - AIM: Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke. We investigated the relationship between ambulatory blood pressure monitoring levels and quantitatively measured WMH volumes among elderly hypertensive patients with well-controlled blood pressure (BP) to re-evaluated effective hypertension management methods to prevent the progression of WMH. METHODS: Participants comprised 84 hypertensive patients aged between 65 and 75 years without symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke or cognitive dysfunction. RESULTS: Linear regression analysis showed that office BP was not associated with WMH volume increases. Raised night-time systolic BP (P = 0.013) were associated with greater WMH volumes during ambulatory blood pressure monitoring. To clarify the effect of asleep systolic BP on WML volume, we then classified patients into two systolic BP groups as follows: <125 mmHg (n = 47) and >=125 mmHg (n = 37). Baseline characteristics were almost similar in both groups, except the dipper type of circadian BP variation was significantly common in the group with night-time systolic BP <125 mmHg. However, WMH volume was greater in the group with night-time systolic BP >=125 mmHg than that in the <125 mmHg group (9.0 +/- 8.4 mL vs 4.1 +/- 4.3 mL, P = 0.015). CONCLUSION: Higher night-time systolic BP levels were observed to contribute greater WMH volumes in elderly hypertensive patients. To prevent the progression of WMH, controlling BP on the basis of ambulatory blood pressure monitoring is important. PMID- 26671161 TI - Altered blood flow in cerebral perforating arteries of rat models of diabetes: A synchrotron radiation microangiographic study toward clinical evaluation of white matter hyperintensities. AB - AIM: As altered blood flow in the cerebral perforating arteries (PA) might be related to development of cerebral white matter hyperintensities, we examined whether the hemodynamic relationship of the PA and middle cerebral artery (MCA) is altered in rat models of diabetes, compared with normal rats and a rat model of sinoatrial denervation (blood pressure fluctuation model). METHODS: We used microangiography with monochromatic synchrotron radiation to measure the diameters of the PA and MCA at 4.5 MUm resolution in five groups of rats: (i) Long-Evans Tokushima Otsuka (LETO); (ii) Otsuka Long-Evans Tokushima Fatty (a model of type 2 diabetes with obesity); (iii) LETO with sinoaortic denervation (LETO + SAD); (iv) F344; and (v) F344 + streptozotocin (a model of type 1 diabetes). RESULTS: Compared with LETO, Otsuka Long-Evans Tokushima Fatty rats showed a significant reduction in the diameter of both PA and MCA, though the PA/MCA diameter ratio was unchanged. In contrast, compared with LETO, LETO + SAD rats showed an increased MCA diameter, and the PA/MCA diameter ratio was decreased. Compared with F344 rats, the MCA diameter was increased in F344 + streptozotocin rats, and the PA/MCA diameter ratio was decreased. Scatter diagrams showed that the diameters of the PA and MCA were essentially independent of each other in the two types of diabetic models. CONCLUSION: PA were consistently visualized at high resolution by means of microangiography using synchrotron radiation. The present results show that rat diabetic models exhibit changes in PA diameter and PA/MCA diameter ratio, which might be related to the development of diabetes-associated cerebral white matter hyperintensities. PMID- 26671162 TI - Left ventricular diastolic dysfunction is directly associated with cerebral white matter lesions in elderly patients. PMID- 26671163 TI - Validation of a simple and reliable visual rating scale of white matter hyperintensity comparable with computer-based volumetric analysis. PMID- 26671164 TI - The role of emotion in ethics and bioethics: dealing with repugnance and disgust. PMID- 26671165 TI - A Moorean argument for the full moral status of those with profound intellectual disability. AB - This paper is about the moral status of those human beings who have profound intellectual disabilities (PIDs). We hold the common sense view that they have equal status to 'normal' human beings, and a higher status than any non-human animal. On the standard account of moral status, this view cannot be sustained. In this paper, we ask whether, in order to be justified in continuing to hold our view, we are obliged to offer an alternative account that does sustain it? Our answer is that we are not. PMID- 26671166 TI - Language Use and Coalition Formation in Multiparty Negotiations. AB - The alignment of bargaining positions is crucial to a successful negotiation. Prior research has shown that similarity in language use is indicative of the conceptual alignment of interlocutors. We use latent semantic analysis to explore how the similarity of language use between negotiating parties develops over the course of a three-party negotiation. Results show that parties that reach an agreement show a gradual increase in language similarity over the course of the negotiation. Furthermore, reaching the most financially efficient outcome is dependent on similarity in language use between the parties that have the most to gain from such an outcome. PMID- 26671167 TI - Structure and Function of Photosystem I-[FeFe] Hydrogenase Protein Fusions: An All-Atom Molecular Dynamics Study. AB - All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein-protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigating protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate. PMID- 26671168 TI - Folic-Acid-Modified Conducting Polymer: Electrochemical Detection of the Cell Attachment. AB - Here, postfunctionalization and bioapplication of a pi-conjugated polymer named 4 [4H-dithieno(3,2-b:2',3'-d)pyrrol-4-yl]aniline (DTP-aryl-NH2 ) are reported, which is successfully synthesized via electropolymerization onto the glassy carbon electrode. Folic acid (FA) is used to modify the amino functional polymer via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N hydroxysuccinimide chemistry for the further steps. The selective adhesion of folate receptor positive cells on the surface is followed by the electrochemical methods. Cyclic voltammetry and electrochemical impedance spectroscopy have been used to characterize stepwise modification of the electroactive surface. After optimization studies such as scan rate during the polymer deposition, FA amount for the efficient surface targeting, incubation time with the cells etc., analytical characterization is carried out. The surface morphologies at each step are imaged by using fluorescence microscopy. PMID- 26671169 TI - Dimpled elastic sheets: a new class of non-porous negative Poisson's ratio materials. AB - In this study, we report a novel periodic material with negative Poisson's ratio (also called auxetic materials) fabricated by denting spherical dimples in an elastic flat sheet. While previously reported auxetic materials are either porous or comprise at least two phases, the material proposed here is non-porous and made of a homogeneous elastic sheet. Importantly, the auxetic behavior is induced by a novel mechanism which exploits the out-of-plane deformation of the spherical dimples. Through a combination of experiments and numerical analyses, we demonstrate the robustness of the proposed concept, paving the way for developing a new class of auxetic materials that significantly expand their design space and possible applications. PMID- 26671170 TI - Adolescents and adults at clinical high-risk for psychosis: age-related differences in attenuated positive symptoms syndrome prevalence and entanglement with basic symptoms. AB - BACKGROUND: The attenuated positive symptoms syndrome (APSS) is considered an at risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under researched. METHOD: Based on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13 17, 18-22 and 23-35 years age groups. RESULTS: Of 175 individuals (age = 20.6 +/- 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 +/- 5.0 v. 23.2 +/- 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11-0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups. CONCLUSIONS: APSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents. PMID- 26671171 TI - Local structural distortion and electrical transport properties of Bi(Ni1/2Ti1/2)O3 perovskite under high pressure. AB - Perovskite-structure materials generally exhibit local structural distortions that are distinct from long-range, average crystal structure. The characterization of such distortion is critical to understanding the structural and physical properties of materials. In this work, we combined Pair Distribution Function (PDF) technique with Raman spectroscopy and electrical resistivity measurement to study Bi(Ni1/2Ti1/2)O3 perovskite under high pressure. PDF analysis reveals strong local structural distortion at ambient conditions. As pressure increases, the local structure distortions are substantially suppressed and eventually vanish around 4 GPa, leading to concurrent changes in the electronic band structure and anomalies in the electrical resistivity. Consistent with PDF analysis, Raman spectroscopy data suggest that the local structure changes to a higher ordered state at pressures above 4 GPa. PMID- 26671173 TI - Confronting Oncologists' Emotions. PMID- 26671172 TI - Antioxidant effects of vitamin C on hemoglobin-based oxygen carriers derived from human cord blood. AB - OBJECTIVE: To investigated the antioxidant protection effects of vitamin C (Vc) on the hemoglobin-based oxygen carriers (HBOCs) solution. METHODS: Three influential variables were studied including the molar ratio of Vc and hemoglobin, pH and temperature. The HBOCs molecules were characterized through spectral analysis, circular dichroism spectra, the oxygen binding curves and the molecular weights. RESULTS: The optimized conditions were molar ratios of above 3, pH of 7.5-8.0 and temperature of 4 degrees C. HBOCs characterization showed no differences before and after Vc addition. CONCLUSION: Antioxidant effects in HBOCs solution could be presented by Vc, indicating the potential application of Vc in HBOCs development. PMID- 26671174 TI - In Reply. PMID- 26671175 TI - Alan Sartorelli: A Personal Remembrance. PMID- 26671177 TI - Dysfunctional vestibular system causes a blood pressure drop in astronauts returning from space. AB - It is a challenge for the human body to maintain stable blood pressure while standing. The body's failure to do so can lead to dizziness or even fainting. For decades it has been postulated that the vestibular organ can prevent a drop in pressure during a position change--supposedly mediated by reflexes to the cardiovascular system. We show--for the first time--a significant correlation between decreased functionality of the vestibular otolith system and a decrease in the mean arterial pressure when a person stands up. Until now, no experiments on Earth could selectively suppress both otolith systems; astronauts returning from space are a unique group of subjects in this regard. Their otolith systems are being temporarily disturbed and at the same time they often suffer from blood pressure instability. In our study, we observed the functioning of both the otolith and the cardiovascular system of the astronauts before and after spaceflight. Our finding indicates that an intact otolith system plays an important role in preventing blood pressure instability during orthostatic challenges. Our finding not only has important implications for human space exploration; they may also improve the treatment of unstable blood pressure here on Earth. PMID- 26671179 TI - Slip-Knot-Loop Suture for Continuous Suturing in Laparoscopy. AB - AIMS: One of the challenges of laparoscopic surgery is the time required to perform intracorporeal knots. This can result in considerably longer operating times when compared with the open approach. An example of this is pediatric laparoscopic pyeloplasty, where extensive laparoscopic suturing is required. To reduce the time suturing, the authors developed a new knotting technique for laparoscopic suturing. MATERIALS AND METHODS: The authors modified a neurosurgical knot technique to speed up intricate continuous suturing, and a simple slip-knot-loop suture was created. Twenty continuous sutures were performed with five "bites" of tissue each. Ten were performed with a conventional intracorporeal knot to anchor the suture (Group 1), and 10 were performed using the slip-knot-looped suture to anchor (Group 2). This new knotting technique was used to perform five bowel anastomoses on pig intestine and tested for leaks by distending them with saline for 5 minutes. RESULTS: The mean time to perform the suture for Group 1 was 300 seconds, and the mean time for Group 2 was 236 seconds. Unpaired two-tailed Student's t test comparing the means was significant (P < .001). No leaks occurred in any of the five anastomoses. CONCLUSIONS: This new slip-knot-loop technique modified for pyeloplasty was easy to use, was quicker than conventional knot tying, and produced safe knots and leak-free anastomoses. This knot is transferable to any laparoscopic procedure where continuous suturing is to be used. PMID- 26671178 TI - Adsorption of sodium diclofenac on graphene: a combined experimental and theoretical study. AB - The interactions of sodium diclofenac drug (s-DCF) with different graphene species were investigated using both first principles calculations based on Density Functional Theory (DFT) and adsorption experiments. Through batch adsorption experiments, it was found that rGO was a good adsorbent for removing the s-DCF drug from aqueous solutions. The general-order kinetic model shows the best fit to the experimental data compared with pseudo-first order and pseudo second order kinetic adsorption models. The equilibrium data (at 25 degrees C) were fitted to the Liu isotherm model. The maximum sorption capacity for adsorption of the s-DCF drug was 59.67 mg g(-1) for rGO. The s-DCF adsorption onto pristine graphene, graphene with a vacancy, reduced oxide graphene (rGO) and functionalized graphene nanoribbons were simulated providing a good understanding of the adsorption process of this molecule on graphene-family surfaces. The results predict a physisorption regime in all cases. Based on these results, the ab initio calculations and the adsorption experiments point out that the graphene family are promising materials for extracting s-DCF from wastewater effluents. PMID- 26671180 TI - Dual-Reporter beta-Cell-Specific Male Transgenic Rats for the Analysis of beta Cell Functional Mass and Enrichment by Flow Cytometry. AB - Mouse beta-cell-specific reporter lines have played a key role in diabetes research. Although the rat provides several advantages, its use has lagged behind the mouse due to the relative paucity of genetic models. In this report we describe the generation and characterization of transgenic rats expressing a Renilla luciferase (RLuc)-enhanced yellow fluorescent protein (YFP) fusion under control of a 9-kb genomic fragment from the rat ins2 gene (RIP7-RLuc-YFP). Analysis of RLuc luminescence and YFP fluorescence revealed that reporter expression is restricted to beta-cells in the adult rat. Physiological characteristics including body weight, fat and lean mass, fasting and fed glucose levels, glucose and insulin tolerance, and beta-cell mass were similar between two RIP7-RLuc-YFP lines and wild-type littermates. Glucose-induced insulin secretion in isolated islets was indistinguishable from controls in one of the lines, whereas surprisingly, insulin secretion was defective in the second line. Consequently, subsequent studies were limited to the former line. We asked whether transgene activity was responsive to glucose as shown previously for the ins2 gene. Exposing islets ex vivo to high glucose (16.7 mM) or in vivo infusion of glucose for 24 hours increased luciferase activity in islets, whereas the fraction of YFP-positive beta-cells after glucose infusion was unchanged. Finally, we showed that fluorescence-activated cell sorting of YFP-positive islet cells can be used to enrich for beta-cells. Overall, this transgenic line will enable for the first time the application of both fluorescence and bioluminescence/luminescence-based approaches for the study of rat beta-cells. PMID- 26671181 TI - Ablation of the Stimulatory G Protein alpha-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D. AB - PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)2D. The PTH receptor couples to multiple G proteins. We here ablated the alpha subunit of the stimulatory G protein (Gsalpha) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (Gsalpha(Sglt2KO) mice). Gsalpha(Sglt2KO) mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 +/-0.01 vs 1.23 +/-0.01 mmol/L; P < .05), reduced serum 1,25(OH)2D (59.3 +/-7.0 vs 102.5 +/-12.2 pmol/L; P < .05), and elevated serum PTH (834 +/-133 vs 438 +/-59 pg/mL; P < .05). PTH induced elevation in urinary cAMP excretion was blunted in Gsalpha(Sglt2KO) mice (2- vs 4-fold over baseline in controls; P < .05). Relative to baseline in controls, PTH-induced reduction in serum phosphate tended to be blunted in Gsalpha(Sglt2KO) mice (-0.39 +/-0.33 vs -1.34 +/-0.36 mg/dL; P = .07). Gsalpha(Sglt2KO) mice showed elevated renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (~3.4- and ~11-fold over controls, respectively; P < .05) and tended to have elevated serum FGF23 (829 +/ 76 vs 632 +/-60 pg/mL in controls; P = .07). Heterozygous mice having constitutive ablation of the maternal Gsalpha allele (E1(m-/+)) (model of pseudohypoparathyroidism type-Ia), in which Gsalpha levels in PT are reduced, also exhibited elevated serum FGF23 (474 +/-20 vs 374 +/-27 pg/mL in controls; P < .05). Our findings indicate that Gsalpha is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D. PMID- 26671183 TI - Gsalpha Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet. AB - In both mice and patients with Albright hereditary osteodystrophy, heterozygous inactivating mutations of Gsalpha, a ubiquitously expressed G protein that mediates receptor-stimulated intracellular cAMP production, lead to obesity and insulin resistance but only when the mutation is present on the maternal allele. This parent-of-origin effect in mice was shown to be due to Gsalpha imprinting in one or more brain regions. The ventromedial hypothalamus (VMH) is involved in the regulation of energy and glucose homeostasis, but the role of Gsalpha in VMH on metabolic regulation is unknown. To examine this, we created VMH-specific Gsalpha deficient mice by mating Gsalpha-floxed mice with SF1-cre mice. Heterozygotes with Gsalpha mutation on either the maternal or paternal allele had a normal metabolic phenotype, and there was no molecular evidence of Gsalpha imprinting, indicating that the parent-of-origin metabolic effects associated with Gsalpha mutations is not due to Gsalpha deficiency in VMH SF1 neurons. Homozygous VMH Gsalpha knockout mice (VMHGsKO) showed no changes in body weight on either a regular or high-fat diet. However, glucose metabolism (fasting glucose, glucose tolerance, insulin sensitivity) was significantly improved in male VMHGsKO mice, with the difference more dramatic on the high-fat diet. In addition, male VMHGsKO mice on the high-fat diet showed a greater anorexigenic effect and increased VMH signal transducer and activator of transcription-3 phosphorylation in response to leptin. These results indicate that VMH Gsalpha/cyclic AMP signaling regulates glucose homeostasis and alters leptin sensitivity in mice, particularly in the setting of excess caloric intake. PMID- 26671182 TI - Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice. AB - Rhythmic events in female reproductive physiology, including ovulation, are tightly controlled by the circadian timing system. The molecular clock, a feedback loop oscillator of clock gene transcription factors, dictates rhythms of gene expression in the hypothalamo-pituitary-ovarian axis. Circadian disruption due to environmental factors (eg, shift work) or genetic manipulation of the clock has negative impacts on fertility. Although the central pacemaker in the suprachiasmatic nucleus classically regulates the timing of ovulation, we have shown that this rhythm also depends on phasic sensitivity to LH. We hypothesized that this rhythm relies on clock function in a specific cellular compartment of the ovarian follicle. To test this hypothesis we generated mice with deletion of the Bmal1 locus in ovarian granulosa cells (GCs) (Granulosa Cell Bmal1 KO; GCKO) or theca cells (TCs) (Theca Cell Bmal1 KO; TCKO). Reproductive cycles, preovulatory LH secretion, ovarian morphology and behavior were not grossly altered in GCKO or TCKO mice. We detected phasic sensitivity to LH in wild-type littermate control (LC) and GCKO mice but not TCKO mice. This decline in sensitivity to LH is coincident with impaired fertility and altered patterns of LH receptor (Lhcgr) mRNA abundance in the ovary of TCKO mice. These data suggest that the TC is a pacemaker that contributes to the timing and amplitude of ovulation by modulating phasic sensitivity to LH. The TC clock may play a critical role in circadian disruption-mediated reproductive pathology and could be a target for chronobiotic management of infertility due to environmental circadian disruption and/or hormone-dependent reprogramming in women. PMID- 26671184 TI - The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice. AB - The human placental GH variant (GH-V) is secreted continuously from the syncytiotrophoblast layer of the placenta during pregnancy and is thought to play a key role in the maternal adaptation to pregnancy. Maternal GH-V concentrations are closely related to fetal growth in humans. GH-V has also been proposed as a potential candidate to mediate insulin resistance observed later in pregnancy. To determine the effect of maternal GH-V administration on maternal and fetal growth and metabolic outcomes during pregnancy, we examined the dose-response relationship for GH-V administration in a mouse model of normal pregnancy. Pregnant C57BL/6J mice were randomized to receive vehicle or GH-V (0.25, 1, 2, or 5 mg/kg . d) by osmotic pump from gestational days 12.5 to 18.5. Fetal linear growth was slightly reduced in the 5 mg/kg dose compared with vehicle and the 0.25 mg/kg groups, respectively, whereas placental weight was not affected. GH-V treatment did not affect maternal body weights or food intake. However, treatment with 5 mg/kg . d significantly increased maternal fasting plasma insulin concentrations with impaired insulin sensitivity observed at day 18.5 as assessed by homeostasis model assessment. At 5 mg/kg . d, there was also an increase in maternal hepatic GH receptor/binding protein (Ghr/Ghbp) and IGF binding protein 3 (Igfbp3) mRNA levels, but GH-V did not alter maternal plasma IGF-1 concentrations or hepatic Igf-1 mRNA expression. Our findings suggest that at higher doses, GH-V treatment can cause hyperinsulinemia and is a likely mediator of the insulin resistance associated with late pregnancy. PMID- 26671186 TI - Photocatalytic Surface-Initiated Polymerization on TiO2 toward Well-Defined Composite Nanostructures. AB - We demonstrate the use of TiO2 nanospheres as the photoinitiator for photocatalytic surface-initiated polymerization for the synthesis of various inorganic/polymer nanocomposites with well-defined structures. The excitation of TiO2 by UV-light irradiation produces electrons and holes which drive the free radical polymerization near its surface, producing core/shell composite nanospheres with eccentric or concentric structures that can be tuned by controlling the surface compatibility between the polymer and the TiO2. When highly porous TiO2 nanospheres were employed as the photoinitiator, polymerization could disintegrate the mesoporous framework and give rise to nanocomposites with multiple TiO2 nanoparticles evenly distributed in the polymer spheres. Thanks to the well-developed sol-gel chemistry of titania, this synthesis is well-extendable to the coating of the polymers on many other substrates of interest such as silica and ZnS by simply premodifying their surface with a thin layer of titania. In addition, this strategy could be easily applied to coating of different types of polymers such as polystyrene, poly(methyl methacrylate), and poly(N-isopropylacrylamide). We expect this photocatalytic surface-initiated polymerization process could provide a platform for the synthesis of various inorganic/polymer hybrid nanocomposites for many interesting applications. PMID- 26671185 TI - Comprehensive Profiling of GPCR Expression in Ghrelin-Producing Cells. AB - To determine the comprehensive G protein-coupled receptor (GPCR) expression profile in ghrelin-producing cells and to elucidate the role of GPCR-mediated signaling in the regulation of ghrelin secretion, we determined GPCR expression profiles by RNA sequencing in the ghrelin-producing cell line MGN3-1 and analyzed the effects of ligands for highly expressed receptors on intracellular signaling and ghrelin secretion. Expression of selected GPCRs was confirmed in fluorescence activated cell-sorted fluorescently tagged ghrelin-producing cells from ghrelin promoter CreERT2/Rosa-CAG-LSL-ZsGreen1 mice. Expression levels of GPCRs previously suggested to regulate ghrelin secretion including adrenergic-beta1 receptor, GPR81, oxytocin receptor, GPR120, and somatostatin receptor 2 were high in MGN3-1 cells. Consistent with previous reports, isoproterenol and oxytocin stimulated the Gs and Gq pathways, respectively, whereas lactate, palmitate, and somatostatin stimulated the Gi pathway, confirming the reliability of current assays. Among other highly expressed GPCRs, prostaglandin E receptor 4 agonist prostaglandin E2 significantly stimulated the Gs pathway and ghrelin secretion. Muscarine, the canonical agonist of cholinergic receptor muscarinic 4, stimulated both the Gq and Gi pathways. Although muscarine treatment alone did not affect ghrelin secretion, it did suppress forskolin-induced ghrelin secretion, suggesting that the cholinergic pathway may play a role in counterbalancing the stimulation of ghrelin by Gs (eg, by adrenaline). In addition, GPR142 ligand tryptophan stimulated ghrelin secretion. In conclusion, we determined the comprehensive expression profile of GPCRs in ghrelin-producing cells and identified two novel ghrelin regulators, prostaglandin E2 and tryptophan. These results will lead to a greater understanding of the physiology of ghrelin and facilitate the development of ghrelin-modulating drugs. PMID- 26671187 TI - Glioblastoma-mesenchymal stem cell communication modulates expression patterns of kinin receptors: Possible involvement of bradykinin in information flow. AB - The most aggressive subtype of brain tumors is glioma WHO grade IV, the glioblastoma (GBM). The present work aims to elucidate the role of kinin receptors in interactions between GBM cells and mesenchymal stem cells (MSC). The GBM cell line U87-MG was stably transfected to express dsRed protein, single cell cloned, expanded, and cultured with MSC, both in the direct co-cultures (DC) and indirect co-cultures (IC) at equal cell number ratio for 72 h. Up- and down regulation of matrix metalloproteases (MMP)-9 expression in U87-MG and MSC cells, respectively, in direct co-culture points to possible MSC participation in tumor invasion. MMP9 expression is in line with significantly increased expression of kinin B1 (B1R) and B2 receptor (B2R) in U87-MG cells and their decreased levels in MSC, as confirmed by quantitative assessment using flow cytometric analysis. Similarly, in indirect cultures (IC), lacking the contact between GBM and MSC cells, an increase of B1 and B2 receptor expression was again noted in U87-MG cells, and no significant changes in kinin receptors in MSC was observed. Functionality of kinin-B1 and B2 receptors was evidenced by stimulation of intracellular calcium fluxes by their respective agonists, des-Arg9-bradykinin (DBK) and bradykinin (BK). Moreover, BK showed a feedback control on kinin receptor expression in mono-cultures, direct and indirect co-cultures. The treatment with BK resulted in down-regulation of B1 and B2 receptors in MSC, with simultaneous up-regulation of these receptors in U87-MG cells, suggesting that functions of BK in information flow between these cells is important for tumor progression and invasion. (c) 2015 International Society for Advancement of Cytometry. PMID- 26671189 TI - Role of social determinants and lifestyle on women's metabolic risk during the perimenopausal transition: results from a cohort study. AB - OBJECTIVE: Social determinants have been understudied in relation to metabolic risk and menopause; this study aimed to identify metabolic risk factors during menopausal transition, changes in lifestyle, and other social determinants. METHODS: The Korean Genetic Epidemiologic Survey Community cohort data available for baseline, 2-year, and 4-year follow-up time points were analyzed. Healthy women ages 45 to 55 years, not taking hormonal therapy, were selected; 1,228 were analyzed. Menopausal transition was categorized as premenopausal, perimenopausal, and postmenopausal. Lifestyle patterns consisted of alcohol consumption, exercise, ever smoking, indirect smoking, and eating breakfast. Generalized estimating equations were used for analysis. RESULTS: During the period of study, roughly 30% had become postmenopausal and metabolic syndrome was found in 11.5% to 14.4%. Controlling for other variables, lower income levels showed more than 2 times greater risk for metabolic syndrome in postmenopausal women and those who continued to menstruate. Body mass index was a consistent factor of metabolic risk, which was more pronounced when analyzed by menopausal status, especially in obese menstruating women (odds ratio 30.72, P < 0.0001). Among women who experienced menopause during the observed time frame, less education and sedentary lifestyle were also significant factors in metabolic risk differences, showing 1.7 times and 1.59 times greater risk, respectively. Such differences in education, income, and sedentary lifestyle as significant risk factors in subgroups according to menstrual status change, may suggest vulnerable points in the transition. CONCLUSIONS: Implications include the need for stronger emphasis on weight control before midlife and experiencing menopause, promoting exercise across the menopausal transition, and supportive policy measures for economically disadvantaged women. PMID- 26671188 TI - A randomized, double-blind, placebo-controlled trial of Chinese herbal medicine granules for the treatment of menopausal symptoms by stages. AB - OBJECTIVE: The study aims to evaluate the effectiveness and safety of Chinese herbal medicine granules Danzhi Qing'e formula (DZQE), Erzhi formula (EZ), and their combination (Combined formula) in the treatment of menopausal symptoms at different stages of menopause. METHODS: Women between the ages of 40 to 60 years, who met menopausal symptoms diagnostic criteria and experienced hot flushes at least 14 times/week in the last 4 weeks, were recruited to participate in a stratified randomized, double-blind, placebo-controlled clinical trial (n = 389). They received a treatment period of 8 weeks and were followed up for 4 weeks. Participants were categorized into two subgroups: 197 in the perimenopausal subgroup (menstrual disorder to 1 y after amenorrhea) and 192 in the early postmenopausal subgroup (1-5 y after amenorrhea). Participants were randomly assigned to placebo or one of the three herbal formula treatments. The primary outcome instrument was the Menopause-Specific Quality of Life (MENQOL) questionnaire. RESULTS: When analyzing the two subgroups together, DZQE markedly decreased the MENQOL total score at the end of 12th week with statistical significance (P = 0.02) and improved vasomotor symptoms after 8 weeks treatment and 4 weeks follow-up (P < 0.05). What is more, the combined formula also greatly improved the participants' vasomotor symptoms compared with placebo after the 4 weeks follow-up. No statistically meaningful difference was observed in any other outcomes among the groups. The results of subgroup analysis showed that DZQE and Combined formula were more effective than placebo in improving MENQOL total score for perimenopausal women at the end of week 12. For typical menopausal symptoms such as hot flushes and night sweats, DZQE displayed more favorable effects on early postmenopausal participants. Compared to placebo, the DZQE both showed statistically significant differences after 8 weeks treatment and 4 weeks follow up. Although at the end of 12th week, DZQE also had better effects than placebo in the perimenopausal subgroup on vasomotor symptoms. Participants in the EZ group did not show a significant difference of any domains in MENQOL compared with participants in the placebo group. CONCLUSIONS: The DZQE formula improves the quality of life for menopausal women, especially for those with vasomotor symptoms during the whole menopausal period. The DZQE and EZ combination formula is effective only on perimenopausal symptoms. PMID- 26671190 TI - Changes in bone mass during the perimenopausal transition in naturally menopausal cynomolgus monkeys. AB - OBJECTIVE: This study measured the differences in bone mineral density and content in relation to changes in serum hormone and bone marker levels during the perimenopausal transition in naturally menopausal cynomolgus monkeys. METHODS: The bone mineral density and content of premenopausal, perimenopausal, and early (0-< 5 y), mid (5-10 y), and late (> 10 y) postmenopausal monkeys were measured at the distal radius and proximal tibia in both metaphysis and diaphysis. Hormonal and bone marker levels were also measured. RESULTS: The serum 17beta estradiol level significantly decreased during late postmenopause, whereas the serum follicle-stimulating hormone levels significantly increased from early postmenopause before declining at late postmenopause. Trabecular bone loss at metaphysis occurred once the animals entered into the perimenopausal period, whereas cortical bone loss gradually and continuously decreased, dependent on the time-course after perimenopause, and was greatest in the late postmenopausal period. Serum bone-specific alkaline phosphatase and urinary N-telopeptide of bone type-1 collagen levels were negatively correlated with the trabecular bone mineral content at metaphysis, whereas serum osteocalcin levels showed a negative correlation with the cortical bone mineral density at the diaphysis. The only positive linear correlation observed was between serum follicle-stimulating hormone and urinary N-telopeptide of bone type-1 collagen levels. CONCLUSIONS: Unlike the ovariectomized monkey models that do not retain the perimenopausal transition, naturally menopausal monkeys elicit different patterns of bone loss during the transition-an abrupt decline in the trabecular metaphysis and a gradual decline in the cortical diaphysis. Naturally menopausal cynomolgus monkeys offer an alternative model for osteoporosis research for postmenopausal women. PMID- 26671191 TI - Relationship between menopause status, attitude toward menopause, and quality of life in Chinese midlife women in Hong Kong. AB - OBJECTIVES: This cross-sectional study aimed to explore the relationship between menopause status and attitude toward menopause, and also its relationship with quality of life (QoL) of Chinese midlife women in Hong Kong. METHODS: Hong Kong Chinese women aged 40 to 59 years were recruited through computer-generated random telephone dialing. Information was obtained through telephone interviews based on a structured questionnaire. Women were classified into 3 groups: premenopausal, perimenopausal, and postmenopausal. Menopause Belief Scale and Utian Quality of Life Scale (QoL) were used to measure respondents' attitude toward menopause and their QoL. Information on social, health, and lifestyle factors was also collected. RESULTS: The mean age of the participants was 49.4 +/ 5.2 years. Respondents generally had a positive attitude toward menopause. Compared with premenopausal women, postmenopausal women were noted to have significantly higher attitude score toward menopause. No significant differences in QoL score were noted among women of the 3 menopause statuses. Stepwise regression analysis showed that women with more positive attitude toward menopause tended to have higher QoL score. Furthermore, better self-reported health status, doing physical activities, higher education level, being married, and non-smoking status were associated with better QoL. CONCLUSIONS: Postmenopausal women tended to have more positive attitude toward menopause. Although menopause status did not seem to be associated with QoL, attitude toward menopause, self-reported health status, as well as social and lifestyle factors were associated with QoL in Chinese midlife women. PMID- 26671192 TI - A neuroprogenitor cell-based mechanism for exercise-enhanced cognition after reproductive senescence? PMID- 26671193 TI - Contraception for midlife women. AB - Despite a decline in fertility, women of older reproductive age who do not desire pregnancy should use contraception until menopause. Unintended pregnancy can be disruptive at any age, but in older women, pregnancy is associated with higher rates of adverse health outcomes for the mother and the fetus because of advanced age and comorbid medical conditions (e.g., hypertension or diabetes). Therefore, providing appropriate contraceptive care to women of older reproductive age is critical. PMID- 26671194 TI - Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens. AB - Pulmonary arterial remodelling is a pathological characteristic of pulmonary arterial hypertension (PAH), which contributes to the development of sustained pulmonary hypertension. The aim of this study was to investigate the effects of dietary Trifolium pratense isoflavones on pulmonary vascular remodelling in experimental broiler pulmonary hypertension syndrome. Exposure to sub thermoneutral environmental temperatures increased broiler's pulmonary hypertension syndrome incidence and raised expression levels of nitric oxide, endothelin and endothelial nitric oxide synthase. Dietary supplementation (20 mg/kg basal diet) with Trifolium pratense isoflavones reduced pulmonary hypertension syndrome incidence and improved pulmonary vascular remodelling without affecting growth performance. The beneficial effect likely came from isoflavone improved pulmonary vascular remodelling. Isoflavone induced inducible nitric oxide synthase expression, which led to increased nitric oxide level. The nitric oxide could mediate vasorelaxation in the lungs. At the same time, the expression of endothelin was downregulated by isoflavone. Dietary supplementation of Trifolium pratense isoflavone might be a potential therapeutic strategy for the treatment of pulmonary hypertension. PMID- 26671195 TI - Historical ambient airborne asbestos concentrations in the United States - an analysis of published and unpublished literature (1960s-2000s). AB - Outdoor concentrations of airborne asbestos have been measured throughout the US over time. However, a thorough review and analysis of these data has not been conducted. The purpose of this study is to characterize asbestos concentrations in ambient air by environment type (urban, rural) and by decade, using measurements collected in the absence of known asbestos emission sources. A total of 17 published and unpublished studies and datasets were identified that reported the results of 2058 samples collected from the 1960s through the 2000s across the US. Most studies did not report asbestos fiber type, and data based on different analytical methods (e.g. Phase Contrast Microscopy, Transmission Electron Microscopy, etc.) were combined in the dataset; however, only fibers >=5 MUm in length were considered. For a small subset of the measurements (n = 186, 9.0%), a conversion factor was used to convert mass-based data (e.g. ng/m(3)) to count-based values (i.e. f/cc >=5 MUm). The estimated overall mean and median ambient asbestos concentrations for the 1960s through 2000s were 0.00093 f/cc and 0.00022 f/cc, respectively. Concentrations generally increased from the 1960s through the early 1980s, after which they declined considerably. While asbestos use decreased throughout the 1970s, these results indicate that ambient concentrations peaked during the early 1980s, which suggests the possible contribution of abatement or demolition activities. Lastly, ambient asbestos concentrations were higher in urban than rural settings, which is consistent with the greater use of asbestos-containing materials in more densely populated areas. PMID- 26671196 TI - Assessment of chronic inhalation non-cancer toxicity for diethylamine. AB - A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose-response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 ug/m(3)). PMID- 26671197 TI - Measured removal rates of chrysotile asbestos fibers from air and comparison with theoretical estimates based on gravitational settling and dilution ventilation. AB - CONTEXT: Industrial hygiene assessments often focus on activity-based airborne asbestos concentration measurements, but few empirical data exist regarding the fiber removal rate from air after activities cease. OBJECTIVE: Grade 7T chrysotile indoor fiber settling (FS) rates were characterized using air sampling (NIOSH Method 7402). MATERIALS AND METHODS: Six replicate events were conducted in a 58 m(3) study chamber (ventilation 3.5 ACH), in which chrysotile contaminated work clothing was manipulated for 15 min followed by 30 min of no activity. The fiber concentration decay constant and removal rate were characterized using an exponential decay model based on the measurements. RESULTS: Breathing zone airborne chrysotile concentrations decreased by 86% within 15-30 min after fiber disturbance, compared to concentrations during active disturbance (p < 0.05). Estimated mean time required for 99% of the phase contrast microscopy-equivalent (PCME) fibers to be removed from air was approximately 30 min (95% CI: 22-57 min). The observed effective FS velocity was 0.0034 m/s. This settling velocity was between 4.5-fold and 180-fold faster than predicted by two different particulate gravitational settling models. Additionally, PCME concentrations decreased approximately 2.5-fold faster than predicted due to air exchange alone (32 versus 79 min to 99% decrease in concentration). DISCUSSION: Other measurement studies have reported similar airborne fiber removal rates, supporting the finding that factors other than gravitational settling and dilution ventilation contribute measurably to PCM fiber removal from air (e.g. impaction, agglomeration). CONCLUSION: Overall, the scientific weight of evidence indicates that the time necessary for removal of 99% of fibers greater than 5 MUm in length (with aspect ratios greater than 3:1) is approximately 20-80 min. PMID- 26671198 TI - Cigarette smoke extract-treated mast cells promote alveolar macrophage infiltration and polarization in experimental chronic obstructive pulmonary disease. AB - OBJECTIVE: Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) and may modulate the immune response of exposed individuals. Mast cell function can be altered by cigarette smoking, but the role of smoking in COPD remains poorly understood. The current study aimed to explore the role of cigarette smoke extract (CSE)-treated mast cells in COPD pathogenesis. METHODS: Cytokine and chemokine expression as well as degranulation of bone marrow-derived mast cells (BMMCs) were detected in cells exposed to immunoglobulin E (IgE) and various doses of CSE. Adoptive transfer of CSE-treated BMMCs into C57BL/6J mice was performed, and macrophage infiltration and polarization were evaluated by fluorescence-activated cell sorting (FACS). Furthermore, a coculture system of BMMCs and macrophages was established to examine macrophage phenotype transition. The role of protease serine member S31 (Prss31) was also investigated in the co culture system and in COPD mice. RESULTS: CSE exposure suppressed cytokine expression and degranulation in BMMCs, but promoted the expressions of chemokines and Prss31. Adoptive transfer of CSE-treated BMMCs induced macrophage infiltration and M2 polarization in the mouse lung. Moreover, CSE-treated BMMCs triggered macrophage M2 polarization via Prss31 secretion. Recombinant Prss31 was shown to activate interleukin (IL)-13/IL-13Ralpha/Signal transducers and activators of transcription (Stat) 6 signaling in macrophages. Additionally, a positive correlation was found between Prss31 expression and the number of M2 macrophages in COPD mice. CONCLUSION: In conclusion, CSE-treated mast cells may induce macrophage infiltration and M2 polarization via Prss31 expression, and potentially contribute to COPD progression. PMID- 26671199 TI - Characterization of a nose-only inhaled phosgene acute lung injury mouse model. AB - CONTEXT: Phosgene's primary mode of action is as a pulmonary irritant characterized by its early latent phase where life-threatening, non-cardiogenic pulmonary edema is typically observed 6-24 h post-exposure. OBJECTIVE: To develop an inhaled phosgene acute lung injury (ALI) model in C57BL/6 mice that can be used to screen potential medical countermeasures. METHODS: A Cannon style nose only inhalation exposure tower was used to expose mice to phosgene (8 ppm) or air (sham). An inhalation lethality study was conducted to determine the 8 ppm median lethal exposure (LCt50) at 24 and 48 h post-exposure. The model was then developed at 1.2 times the 24 h LCt50. At predetermined serial sacrifice time points, survivors were euthanized, body and lung weights collected, and lung tissues processed for histopathology. Additionally, post-exposure clinical observations were used to assess quality of life. RESULTS AND DISCUSSION: The 24 hour LCt50 was 226 ppm*min (8 ppm for 28.2 min) and the 48-hour LCt50 was 215 ppm*min (8 ppm for 26.9 min). The phosgene exposed animals had a distinct progression of clinical signs, histopathological changes and increased lung/body weight ratios. Early indicators of a 1.2 times the 24-hour LCt50 phosgene exposure were significant changes in the lung-to-body weight ratios by 4 h post exposure. The progression of clinical signs and histopathological changes were important endpoints for characterizing phosgene-induced ALI for future countermeasure studies. CONCLUSION: An 8 ppm phosgene exposure for 34 min (1.2 * LCt50) is the minimum challenge recommended for evaluating therapeutic interventions. The predicted higher mortality in the phosgene-only controls will help demonstrate efficacy of candidate treatments and increase the probability that a change in survival rate is statistically significant. PMID- 26671200 TI - Autocrine Signaling and Quorum Sensing: Extreme Ends of a Common Spectrum. AB - 'Secrete-and-sense cells' can communicate by secreting a signaling molecule while also producing a receptor that detects the molecule. The cell can potentially 'talk' to itself ('self-communication') or talk to neighboring cells with the same receptor ('neighbor communication'). The predominant forms of secrete-and sense cells are self-communicating 'autocrine cells', which are largely found in animals, and neighbor-communicating 'quorum sensing cells', which are mostly associated with bacteria. While assumed to function independently of one another, recent studies have discovered quorum-sensing organs and autocrine-signaling microbes. Moreover, similar types of genetic circuit control many autocrine and quorum-sensing cells. Here, we outline these recent findings and explain how autocrine and quorum sensing are two sides of a many-sided 'dice' created by the versatile secrete-and-sense cell. PMID- 26671201 TI - Use of Hip Arthroscopy and Risk of Conversion to Total Hip Arthroplasty: A Population-Based Analysis. AB - PURPOSE: To use population-level data to (1) evaluate the conversion rate of total hip arthroplasty (THA) within 2 years of hip arthroscopy and (2) assess the influence of age, arthritis, and obesity on the rate of conversion to THA. METHODS: We used the State Ambulatory Surgery Databases and State Inpatient Databases for California and Florida from 2005 through 2012, which contain 100% of patient visits. Hip arthroscopy patients were tracked for subsequent primary THA within 2 years. Out-of-state patients and patients with less than 2 years follow-up were excluded. Multivariate analysis identified risks for subsequent hip arthroplasty after arthroscopy. RESULTS: We identified 7,351 patients who underwent hip arthroscopy with 2 years follow-up. The mean age was 43.9 +/- 13.7 years, and 58.8% were female patients. Overall, 11.7% of patients underwent THA conversion within 2 years. The conversion rate was lowest in patients aged younger than 40 years (3.0%) and highest in the 60- to 69-year-old group (35.0%) (P < .001). We found an increased risk of THA conversion in older patients and in patients with osteoarthritis or obesity at the time of hip arthroscopy. Patients treated at high-volume hip arthroscopy centers had a lower THA conversion rate than those treated at low-volume centers (15.1% v 9.7%, P < .001). CONCLUSIONS: Hip arthroscopy is performed in patients of various ages, including middle-aged and elderly patients. Older patients have a higher rate of conversion to THA, as do patients with osteoarthritis or obesity. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26671202 TI - Fractional Microneedling: A Novel Method for Enhancement of Topical Anesthesia Before Skin Aesthetic Procedures. AB - BACKGROUND: Skin microneedling or fractional microneedle therapy is a recent approach used for skin rejuvenation or to enhance transdermal delivery of topical medications. OBJECTIVE: The authors evaluated the efficacy of skin microneedling, using an automated device, to enhance the numbing effect of topical anesthesia, used before minimally invasive aesthetic approaches. METHODS: Fifteen patients, looking for treatment of atrophic acne scars, were subjected to randomized split face study comparing automated fractional skin microneedling (0.5 mm depth) followed by application of topical anesthetic cream (Lidocaine 2.5% + Prilocaine 2.5%) on one side of face, with topical anesthesia alone on the other side, followed by full face fractional microneedling treatment for postacne scars (2.5 mm depth). RESULTS: The treated sides (fractional needling + topical anesthesia) had significantly lower pain scores when compared with the nontreated sides (topical anesthesia alone). The scores of pain sensation, during the whole procedure, were statistically significantly (p < .0001) less on the treated sides (3.10 +/- 1.09) of the face when compared with the nontreated sides (5.37 +/- 0.99). There was also a statistically significant (p < .0001) difference in pain sensation scores between the 2 sides of the face after horizontal passes, as the mean scores of the treated and nontreated sides were 3.93 +/- 0.59 and 6.20 +/- 0.41, respectively. LIMITATIONS: The small number of patients, yet the results show a significant difference. CONCLUSION: Application of topical anesthesia for minimally invasive aesthetic procedures can be enhanced with fractional microneedling pretreatment. PMID- 26671203 TI - Commentary on Novel Polydioxanone Multifilament Scaffold Device for Tissue Regeneration. PMID- 26671204 TI - Novel Polydioxanone Multifilament Scaffold Device for Tissue Regeneration. AB - BACKGROUND: Facial aging is the result of intrinsic and extrinsic factors that lead to gradual reduction of dermal extracellular components and skin elasticity and wrinkle formation. A novel stent-shaped biodegradable and biocompatible scaffold device braided with absorbable polydioxanone (PDO) multifilaments was recently marketed for tissue suturing and augmentation. OBJECTIVE: To explore tissue regeneration profiles following implantation of the stent-shaped hollow scaffold in rats and mini-pigs. MATERIALS AND METHODS: The scaffold device was implanted under the panniculus carnosus of rat dorsal skin and in the subcutaneous layer of mini-pig dorsal skin. Tissue samples were harvested and histologically evaluated after 3 days and 1, 2, 4, and 12 weeks for rats and after 1, 2, 4, 8, and 12 weeks for mini-pigs. RESULTS: Type III collagen was slowly replaced by Type I collagen in the scaffold. Cells from the surrounding tissue infiltrated the hollow space of the scaffold, which induced de novo tissue regeneration in this space. CONCLUSION: The novel stent-shaped scaffold used here may be useful for stimulated tissue remodeling of aged skin, collagen synthesis, and partial restoration of dermal matrix components. The cosmetic purpose of this novel soft tissue augmentation device should be clinically investigated in long term studies. PMID- 26671205 TI - An Elongated Leading Edge Facilitates Rotation Flap Closure: In Vivo Demonstration. AB - BACKGROUND: Variation in the design of a rotation flap may affect wound closure tension. Lengthening the leading edge of a rotation flap has been a method of reducing the tension of closure in the primary motion. An in vitro study negating this tenant has been published. OBJECTIVE: The authors set out to design an in vivo experiment to determine if lengthening the leading edge of a rotation flap has the effect of reducing closure tension in the primary motion of the repair. MATERIALS AND METHODS: An animal study approved by Institutional Animal Care and Use Committee was undertaken in a pig model. A tension-measuring apparatus was designed using Teflon-coated wires and digital tensiometers. Rotation flaps of a standard design and with elongated leading edges were incised on the flanks of pigs under general anesthesia. Flap closure tensions were measured at points along the leading edge of the flap and in the secondary motion. RESULTS: Elongating the leading edge of a flap led to a statistically significant reduction in closure tension in the primary motion of the flap and at the flap tip. The secondary motion closure tensions were essentially unaffected. CONCLUSION: The authors confirm that elongating the leading edge of a standard rotation flap will reduce closure tension in the primary flap motion. PMID- 26671206 TI - Effectiveness and Advantages of On-Site Pathology Services in the Care of Patients With Nonmelanoma Skin Cancer. AB - BACKGROUND: On-site pathology services are an integral part of many dermatology and surgical dermatology practices in the United States. OBJECTIVE: Assess the effectiveness and advantages of on-site pathology services. METHODS: Biopsy data from 7 practices with on-site pathology services were reviewed to determine the diagnostic accuracy of malignancies from all lesional biopsies. Patient preference and convenience were queried and measured with satisfaction surveys. RESULTS: Of note, 1,052/1,379 (76.3%) of biopsies demonstrated a malignancy. Most patients underwent treatment of malignant lesions on a different day than the biopsy. Of the patients who scheduled a return visit for surgery on a later date, 42/246 (17.1%) reported incurring additional costs and 44/249 (17.7%) had a relative/friend who was inconvenienced. CONCLUSION: On-site pathology services provide efficient, effective, and convenient care for skin cancer patients. Fellowship-trained dermatologic surgeons use on-site pathology services to diagnose and treat clinically relevant nonmelanoma skin cancer. PMID- 26671207 TI - An Investigation on the Influence of Hyaluronic Acid on Polidocanol Foam Stability. AB - BACKGROUND: Foam sclerotherapy is an effective treatment strategy for varicose veins and venous malformations. Foam stability varies according to foam composition, volume, and injection technique. OBJECTIVE: To evaluate the stability of polidocanol (POL) foam with the addition of hyaluronic acid (HA). MATERIALS AND METHODS: Group A: 2 mL of 1% POL + 0 mL of 1% HA + 8 mL of air; Group B: 2 mL of 1% POL + 0.05 mL of 1% HA + 8 mL of air; Group C: 2 mL of 1% POL + 0.1 mL of 1% HA + 8 mL of air. Tessari's method was used for foam generation. The half-life, or the time for a volume of foam to be reduced to half of its original volume, was used to evaluate foam stability. Five recordings were made for each group. RESULTS: The half-life was 142.8 (+/-4.32) seconds for 1% POL without the addition of HA, 310.6 (+/-7.53) seconds with the addition of 0.05 mL of 1% HA, and 390.4 (+/-13.06) seconds with the addition of 0.1 mL of 1% HA. CONCLUSION: The stability of POL foam was highly increased by the addition of small amounts of HA. PMID- 26671209 TI - Taint: an examination of the lived experiences of stigma and its lingering effects for eight sex industry experts. AB - As part of a larger study examining the effects of the design of the off-street sex industry on sex worker's health and safety practices, eight sex work experts who had experience as sex workers and as advocates and service providers were interviewed to garner their community engagement expertise in shaping the research. During narrative interviews, these experts discussed how stigma influenced their personal lives and their social justice work among sex workers. Their insights into stigma are unique to the literature because our experts simultaneously confronted direct instances of stigma that were a part of their personal and professional lives, sometimes concealing their sex work histories during the course of their professional support and advocacy work. As a result of this concealment, and because of how sex workers are sometimes mistreated, experts experienced stigma vicariously (indirectly) when their own sex work histories were not apparent. As a result of these experiences, participants became proficient at managing discrediting information about themselves when in the presence of those they mistrusted. They supported sex workers through stigmatising ordeals by using knowledge gained from these intersecting direct and vicarious experiences stigma, continuously building capacity within themselves and among other sex workers to resist stigma. PMID- 26671210 TI - Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicine has become an important issue on the global scale during the past decade. Among drugs of natural origin, special place belongs to essential oils, known as strong antimicrobial agents that can be used to combat antibiotic-resistant bacteria. Eucalyptus camaldulensis leaves are traditional herbal remedy used for various purposes, including treatment of infections. The aim of this study was to determine antimicrobial potential of two E. camaldulensis essential oils against multi-drug resistant (MDR) Acinetobacter baumannii wound isolates and to examine possible interactions of essential oils with conventional antimicrobial agents. MATERIALS AND METHODS: Chemical composition of essential oils was determined by gas chromatography-mass spectrometry analysis (GC-MS). MIC values of essential oils against A. baumannii strains were estimated by modified broth microdilution method. The components responsible for antimicrobial activity were detected by bioautographic analysis. The potential synergy between the essential oils and antibiotics (ciprofloxacin, gentamicin and polymyxin B) was examined by checkerboard method and time kill curve. RESULTS: The dominant components of both essential oils were spatulenol, cryptone, p-cimene, 1,8-cineole, terpinen-4-ol and beta-pinene. The detected MICs for the E. camaldulensis essential oils were in range from 0.5 to 2 MUl mL(-1). The bioautographic assay confirmed antibacterial activity of polar terpene compounds. In combination with conventional antibiotics (ciprofloxacin, gentamicin and polymyxin B), the examined essential oils showed synergistic antibacterial effect in most of the cases, while in some even re-sensitized MDR A. baumannii strains. The synergistic interaction was confirmed by time-kill curves for E. camaldulensis essential oil and polymyxin B combination which reduced bacterial count under detection limit very fast, i.e. after 6h of incubation. CONCLUSIONS: The detected anti-A. baumannii activity of E. camaldulensis essential oils justifies traditional use of this plant. The proven E. camaldulensis essential oil synergistic interactions with conventional antibiotics could lead to the development of new treatment strategies of infections caused by MDR A. baumannii strains in the term of antibiotic dose reduction. PMID- 26671211 TI - Evaluation of the general public's knowledge, views and practices relating to appropriate antibiotic use in Qatar. AB - OBJECTIVE: Studies completed internationally have demonstrated an alarming number of patients believed antibiotics are indicated in the treatment of viral infections and other self-limited illnesses. Evaluation of patient practices relating to antibiotics have also demonstrated inappropriate use. Antibiotic misuse by patients and practitioners has been identified as a factor in the development of resistance. Current knowledge, views and practices relating to antibiotic use in Qatar is unknown. The primary objective of this study was to evaluate the general population's current antimicrobial knowledge, views and practices in Qatar. METHODS: This study was designed as a self-administered cross sectional survey. Eligible participants were residents of Qatar who were over the age of 18 and spoke English or Arabic. The questionnaire was developed based on previously published literature and objectives of this study. Data were collected at community pharmacies in Doha, Qatar. KEY FINDINGS: The majority of participants (95.8%) had taken antibiotics in the past. The median knowledge score of the study population was 4/8. Misconceptions relating to use of antibiotics for treatment of viral infections were common. Inappropriate use as evident by hoarding of antibiotics for future use and sharing antibiotics with family or friends was also identified in this study population. CONCLUSION: Community pharmacists in Qatar have an opportunity to improve knowledge of the general population regarding appropriate indications of antibiotics and risk of resistance with inappropriate use. PMID- 26671212 TI - [Critical appraisal of clinical practice guidelines: A necessary exercise]. PMID- 26671213 TI - Systematic Differences between Cochrane and Non-Cochrane Meta-Analyses on the Same Topic: A Matched Pair Analysis. AB - BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non Cochrane reviews reported significantly higher effect sizes (P< 0.001) and lower precision (P<0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSION: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question. PMID- 26671214 TI - Enhanced production of optically pure d (-) lactic acid from nutritionally rich Borassus flabellifer sugar and whey protein hydrolysate based-fermentation medium. AB - The aim of this study is to optimize the production of optically pure d (-) lactic acid (DLA) employing a cost-effective production medium. Based on the designed biomass approach, Sporolactobacillus inulinus NBRC 13595 was found to exhibit high DLA titer (19.0 g L-1 ) and optical purity (99.6%). A cost-effective medium was constituted using Palmyra palm jaggery (PJ) from Borassus flabellifer and whey protein hydrolysate (WPH) as carbon and nitrogen sources, respectively. Plackett-Burman design indicated that PJ, WPH, and MnSO4 as significant variables influence DLA production. A rotatable central composite design and response surface methodology were used to optimize the PJ and WPH concentrations. A maximum DLA titer (170.14 g L-1 ) was predicted for 222.24 g L-1 of PJ and 11.99 g L-1 of WPH, respectively. Fermentation experimental results exhibited a maximum DLA titer (189.0 +/- 8.53 g L-1 ) and productivity (5.25 +/- 0.24 g L-1 H-1 ), which is the highest ever reported for DLA production from a renewable feedstock in the batch process. The present investigation substantiates that the potential application of economically viable raw feedstocks (PJ and WPH) for enhanced DLA production, which is attributed to 2.5-fold reduction in DLA production cost compared with conventional medium. PMID- 26671216 TI - A Clinically Relevant Method of Analyzing Continuous Change in Robotic Upper Extremity Chronic Stroke Rehabilitation. AB - BACKGROUND: Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. OBJECTIVE: To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. METHODS: A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. RESULTS: Significant improvement (P < .05) in movement time across the intervention (pre vs post) was similar between the groups but there were group differences for changes between and within sessions (P < .05). The 2-term exponential function revealed a fast and slow component of learning that described performance across consecutive blocks. The RCM identified individuals who were above or below the marginal model. CONCLUSIONS: The expanded analyses indicated that changes across time can occur in different ways but achieve similar goals and may be influenced by individual factors such as initial movement time. These findings will guide decisions regarding treatment planning based on rates of motor relearning during upper extremity stroke robotic interventions. PMID- 26671215 TI - Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats. AB - Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious. PMID- 26671217 TI - Improving Motor Corticothalamic Communication After Stroke Using Real-Time fMRI Connectivity-Based Neurofeedback. AB - BACKGROUND: Two thirds of stroke survivors experience motor impairment resulting in long-term disability. The anatomical substrate is often the disruption of cortico-subcortical pathways. It has been proposed that reestablishment of cortico-subcortical communication relates to functional recovery. OBJECTIVE: In this study, we applied a novel training protocol to augment ipsilesional cortico subcortical connectivity after stroke. Chronic stroke patients with severe motor impairment were provided online feedback of blood-oxygenation level dependent signal connectivity between cortical and subcortical regions critical for motor function using real-time functional magnetic resonance imaging neurofeedback. RESULTS: In this proof of principle study, 3 out of 4 patients learned to voluntarily modulate cortico-subcortical connectivity as intended. CONCLUSIONS: Our results document for the first time the feasibility and safety for patients with chronic stroke and severe motor impairment to self-regulate and augment ipsilesional cortico-subcortical connectivity through neurofeedback using real time functional magnetic resonance imaging. PMID- 26671218 TI - A fully dynamic multi-compartmental poroelastic system: Application to aqueductal stenosis. AB - This study proposes the implementation of a fully dynamic four-network poroelastic model which is underpinned by multiple-network poroelastic theory (MPET), in order to account for the effects of varying stages of aqueductal stenosis and atresia during acute hydrocephalus. The innovation of the fully dynamic MPET implementation is that it avoids the commonplace assumption of quasi steady behaviour; instead, it incorporates all transient terms in the casting of the equations and in the numerical solution of the resulting discrete system. It was observed that the application of mild stenosis allows for a constant value of amalgamated ventricular displacement in under 2.4h, whereas the application of a severe stenosis delays this settlement to approximately 10h. A completely blocked aqueduct does not show a clear sign of reaching a steady ventricular displacement after 24h. The increasing ventricular pressure (complemented with ventriculomegaly) during severe stenosis is causing the trans-parenchymal tissue region to respond, and this coping mechanism is most attenuated at the regions closest to the skull and the ventricles. After 9h, the parenchymal tissue shows to be coping well with the additional pressure burden, since both ventriculomegaly and ventricular CSF (cerebrospinal fluid) pressure show small increases between 9 and 24h. Localised swelling in the periventricular region could also be observed through CSF fluid content, whilst dilation results showed stretch and compression of cortical tissue adjacent to the ventricles and skull. PMID- 26671219 TI - On a sparse pressure-flow rate condensation of rigid circulation models. AB - Cardiovascular simulation has shown potential value in clinical decision-making, providing a framework to assess changes in hemodynamics produced by physiological and surgical alterations. State-of-the-art predictions are provided by deterministic multiscale numerical approaches coupling 3D finite element Navier Stokes simulations to lumped parameter circulation models governed by ODEs. Development of next-generation stochastic multiscale models whose parameters can be learned from available clinical data under uncertainty constitutes a research challenge made more difficult by the high computational cost typically associated with the solution of these models. We present a methodology for constructing reduced representations that condense the behavior of 3D anatomical models using outlet pressure-flow polynomial surrogates, based on multiscale model solutions spanning several heart cycles. Relevance vector machine regression is compared with maximum likelihood estimation, showing that sparse pressure/flow rate approximations offer superior performance in producing working surrogate models to be included in lumped circulation networks. Sensitivities of outlets flow rates are also quantified through a Sobol' decomposition of their total variance encoded in the orthogonal polynomial expansion. Finally, we show that augmented lumped parameter models including the proposed surrogates accurately reproduce the response of multiscale models they were derived from. In particular, results are presented for models of the coronary circulation with closed loop boundary conditions and the abdominal aorta with open loop boundary conditions. PMID- 26671220 TI - Biomedical microfluidic devices by using low-cost fabrication techniques: A review. AB - One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft-lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non-lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples. PMID- 26671221 TI - Red blood cells radial dispersion in blood flowing through microchannels: The role of temperature. AB - The behavior of suspensions of individual blood cells, such as red blood cells (RBCs), flowing through microvessels and microfluidic systems depend strongly on the hematocrit (Hct), microvessel topology and cell properties. Although it is well known that blood rheological properties are temperature dependent, to the best of our knowledge no work has studied the role of the temperature on the RBCs dispersion. A powerful way to investigate this latter effect is through a high speed video microscopy system, which provides detailed flow measurements of each individual RBC. Hence, the effect of temperature on the RBCs dispersion flowing through a 100MUm glass capillary was examined by means of a confocal micro-PTV system. Hundreds of labeled RBCs were tracked at moderate Hct (12%) and at four different temperatures, i.e., 25 degrees C, 32 degrees C, 37 degrees C and 42 degrees C. The results yielded an enhancement of the RBCs diffusion as the temperature increases. Hence, our findings show that RBCs radial dispersion is temperature dependent and as a result the temperature should not be ignored in future blood flow studies. We believe that this finding is important for a better understanding of blood mass transport mechanisms under both physiological and pathological conditions. PMID- 26671222 TI - Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model. AB - BACKGROUND: During the erythrocytic stage in humans, malaria parasites digest haemoglobin of the host cell, and the toxic haem moiety crystallizes into haemozoin. Chloroquine acts by forming toxic complexes with haem molecules and interfering with their crystallization. In chloroquine-resistant strains, the drug is excluded from the site of action, which causes the parasites to accumulate less chloroquine in their acid food vacuoles than chloroquine sensitive parasites. 3-Hydroxylpyridin-4-ones are known to chelate iron; hydroxypyridone-chloroquine (HPO-CQ) hybrids were synthesized in order to determine whether they can inhibit parasites proliferation in the parasitic digestive vacuole by withholding iron from plasmodial parasite metabolic pathway. METHODS: Two HPO-CQ hybrids were tested against Plasmodium falciparum chloroquine sensitive (D10 and 3D7) and -resistant strains (Dd2 and K1). The pharmacokinetic properties of active compounds were determined using a mouse model and blood samples were collected at different time intervals and analysed using LC-MS/MS. For in vivo efficacy the mice were infected with Plasmodium berghei in a 4-day Peters' test. The parasitaemia was determined from day 3 and the course of the infection was followed by microscopic examination of stained blood films every 2 3 days until a rise in parasitaemia was observed in all test subjects. RESULTS: IC50 values of the two compounds for sensitive and resistant strains were 0.064 and 0.047 uM (compound 1), 0.041 and 0.122 uM (compound 2) and 0.505 and 0.463 uM (compound 1), 0.089 and 0.076 uM (compound 2), respectively. Pharmacokinetic evaluation of these compounds showed low oral bioavailability and this affected in vivo efficacy when compounds were dosed orally. However, when dosed intravenously compound 1 showed a clearance rate of 28 ml/min/kg, an apparent volume of distribution of 20 l/kg and a half-life of 4.3 h. A reduction in parasitaemia was observed when compound 1 was dosed intravenously for four consecutive days in P. berghei-infected mice. However, a rise in parasitaemia levels was observed on day 6 and on day 9 for chloroquine-treated mice. CONCLUSION: The hybrid compounds that were tested were able to reduce parasitaemia levels in P. berghei-infected mice when dosed intravenously, but parasites recrudesced 24 h after the administration of the least dose. Despite low oral bioavailability, the IV data obtained suggests that further structural modifications may lead to the identification of more HPO-CQ hybrids with improved pharmacokinetic properties and in vivo efficacy. PMID- 26671223 TI - Iridium-Catalyzed C-C Coupling of a Simple Propargyl Ether with Primary Alcohols: Enantioselective Homoaldol Addition via Redox-Triggered (Z)-Siloxyallylation. AB - A chiral iridium complex formed in situ from [Ir(cod)Cl]2 and (R)-H8-BINAP is found to catalyze the direct enantioselective C-C coupling of a simple propargyl ether, TIPSOCH2C=CH, with primary alcohols to form gamma-hydroxy (Z)-enol silanes with uniformly high enantioselectivity and complete alkene (Z)-stereoselectivity. As corroborated by deuterium labeling studies, these studies represent the first examples of 1,2-hydride shift-enabled pi-allyl formation in the context of iridium catalysis. PMID- 26671224 TI - Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled. AB - Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too. PMID- 26671226 TI - Is utility-based quality of life associated with overweight in children? Evidence from the UK WAVES randomised controlled study. AB - BACKGROUND: Quality-Adjusted Life Years (QALYs) are often used to make judgements about the relative cost-effectiveness of competing interventions and require an understanding of the relationship between health and health-related quality of life (HRQOL) when measured in utility terms. There is a dearth of information in the literature concerning how childhood overweight is associated with quality of life when this is measured using utilities. This study explores how weight is associated with utility-based HRQOL in 5-6 year olds and examines the psychometric properties of a newly developed pediatric utility measure - the CHU9D instrument. METHODS: Weight and HRQOL were examined using data collected from 1334 children recruited within a UK randomised controlled trial (WAVES) (ISRCTN97000586). Utility-based HRQOL was measured using the CHU9D, and general HRQOL measured using the PedsQL instrument. The association between weight and HRQOL was examined through a series of descriptive and multivariate analysis. The construct validity of the CHU9D was further assessed in relation to weight status, in direct comparison to the PedsQL instrument. RESULTS: The HRQOL of children who were either overweight or obese was not statistically different from children who were healthy or underweight. This result was the same for when HRQOL was measured in utility terms using the CHU9D instrument, and in general terms using the PedsQL instrument. Furthermore, the results support the construct validity of the newly developed CHU9D as the PedsQL total HRQOL scores corresponded well with the individual CHU9D dimensions. CONCLUSION: At age 5-6 years, the inverse association between overweight and HRQOL is not being captured by either the utility-based CHU9D instrument nor the PedsQL instrument. This result has implications for how the cost-effectiveness of childhood obesity interventions is measured in children aged 5-6 years. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN97000586 19(th) May 2010. PMID- 26671227 TI - Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp. AB - BACKGROUND: An in vitro electrophysiological assay system, which can assess compound effects and thus show cardiotoxicity including arrhythmia risks of test drugs, is an essential method in the field of drug development and toxicology. METHODS: In this study, high-throughput electrophysiological recordings of human embryonic kidney (HEK 293) cells and Chinese hamster ovary (CHO) cells stably expressing human ether-a-go-go related gene (hERG) were performed utilizing an automated 384-well-patch-clamp system, which records up to 384 cells simultaneously. hERG channel inhibition, which is closely related to a drug induced QT prolongation and is increasing the risk of sudden cardiac death, was investigated in the high-throughput screening patch-clamp system. RESULTS: In the automated patch-clamp measurements performed here, Kv currents were investigated with high efficiency. Various hERG channel blockers showed concentration dependent inhibition, the 50 % inhibitory concentrations (IC50) of those blockers were in good agreement with previous reports. CONCLUSIONS: The high-throughput patch-clamp system has a high potential in the field of pharmacology, toxicology, and cardiac physiology, and will contribute to the acceleration of pharmaceutical drug development and drug safety testing. PMID- 26671228 TI - The association of peroxisome proliferator-activated receptor alpha with diabetic retinopathy, and additional gene-obesity interaction in Chinese type 2 diabetes mellitus patients. AB - AIMS: To investigate the impact of peroxisome proliferator-activated receptor alpha (PPAR alpha) SNPs and gene-obesity interaction on diabetic retinopathy (DR) susceptibility in a Chinese Han population. METHODS: A total of 812 patients (373men, 439 women) with type 2 diabetes mellitus (T2DM), with a mean age of 53.3+/-14.0 years old, were selected, including 402 diabetic retinopathy patients and 410 controls. Three single nucleotide polymorphisms (SNPs) were selected for genotyping in the case-control study: rs4253778, rs135539 and rs1800206. Generalised multifactor dimensionality reduction (GMDR) and logistic regression model was used to examine the association and interaction between SNP and obesity on DR, odds ratio (OR) and 95% confident interval (95%CI) were calculated. RESULTS: The carriers of homozygous mutant of rs1800206 SNP revealed decreased DR risk than those with wild-type homozygotes, OR (95%CI) was 0.78 (0.66-0.94). GMDR analysis indicated a significant two-locus model (p=0.0107) involving rs1800206 and abdominal obesity, indicating a potential interaction among rs1800206 and abdominal obesity. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. We also found that subjects with abdominal obesity and LV or VV genotype have lowest DR risk, compared to subjects with normal WC and LL genotype, OR (95%CI) was 0.39 (0.30 0.74), after covariates adjustment. CONCLUSIONS: Our results support an important association between rs1800206 minor allele of PPAR alpha and DR, and the interaction analysis also shown a combined effect of Leu162 allele-abdominal obesity interaction on DR. PMID- 26671229 TI - Ontario suspends unvaccinated children from school and proposes mandatory classes for parents. PMID- 26671230 TI - A first report of leptospirosis after liver transplantation. AB - Leptospirosis has been rarely reported in solid organ transplant recipients. We report the first case to our knowledge of leptospirosis in a liver transplant recipient who developed jaundice and renal insufficiency. We describe his favorable clinical progression and discuss the possible mechanisms involved in the more benign disease course. We also review the previously published cases of leptospirosis in solid organ transplant recipients. Although this disease does not appear to present any particularities in this context, we highlight the importance of clinical suspicion in this setting, particularly after liver transplantation. PMID- 26671237 TI - Optimizing sgRNA structure to improve CRISPR-Cas9 knockout efficiency. AB - BACKGROUND: Single-guide RNA (sgRNA) is one of the two key components of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing system. The current commonly used sgRNA structure has a shortened duplex compared with the native bacterial CRISPR RNA (crRNA)-transactivating crRNA (tracrRNA) duplex and contains a continuous sequence of thymines, which is the pause signal for RNA polymerase III and thus could potentially reduce transcription efficiency. RESULTS: Here, we systematically investigate the effect of these two elements on knockout efficiency and showed that modifying the sgRNA structure by extending the duplex length and mutating the fourth thymine of the continuous sequence of thymines to cytosine or guanine significantly, and sometimes dramatically, improves knockout efficiency in cells. In addition, the optimized sgRNA structure also significantly increases the efficiency of more challenging genome-editing procedures, such as gene deletion, which is important for inducing a loss of function in non-coding genes. CONCLUSIONS: By a systematic investigation of sgRNA structure we find that extending the duplex by approximately 5 bp combined with mutating the continuous sequence of thymines at position 4 to cytosine or guanine significantly increases gene knockout efficiency in CRISPR-Cas9-based genome editing experiments. PMID- 26671238 TI - Medicine use and disease control among adolescents with asthma. AB - PURPOSE: Pharmacological treatment is a cornerstone in asthma management, but there is limited evidence on how adolescents use their medication and to what extent their asthma is under control. Therefore, the aim of this study was to compare self-reported and register-based medicine use in asthmatic adolescents. Furthermore, we investigated the association between medicine use, patient characteristics, and degree of asthma control. METHODS: Cross-sectional analyses of 331 adolescents with asthma from a population-based birth cohort linked to data from the Swedish Prescribed Drug Register. Adolescents' asthma medicine use was assessed with three approaches: self-reported medicine use, self-reported use of someone else's medicines, and dispensed medicines from pharmacies during an 18 month period. Medicine use in adolescents with and without asthma control were compared. RESULTS: In total, 82% reported use of asthma medicines, 10 % reported use of someone else's medicines, and 62% were dispensed asthma medicines from pharmacies. Among adolescents with self-reported medicine use, 22% (n = 60) were neither dispensed medicines nor using someone else's medicines. The majority of those using someone else's medicines had also been dispensed asthma medicine (22 out of 33). Among adolescents with asthma, 176 were fully controlled and 155 were uncontrolled. Also, boys had higher odds of having asthma control than girls. CONCLUSION: Most adolescents with asthma reported use of asthma medicines, but a considerable proportion were neither dispensed any medicines nor using someone else's medicines. Girls were less likely to achieve asthma control. It is important to combine data sources to understand medicine use among adolescents with asthma. PMID- 26671239 TI - First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany. AB - OBJECTIVES: The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma. METHODS: A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison. RESULTS: One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65 0.75; MPT vs. MP, OS: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR for non response 0.92, 0.88-0.95); but had a higher risk of developing any grade 3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 1.43 2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63 1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes. CONCLUSIONS: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT. PMID- 26671240 TI - Influence of baseline low-density lipoprotein cholesterol values on statin therapy persistence. AB - PURPOSE: Persistence to statins is low, in part due to lack of perception of cardiovascular (CV) risk. High values of low-density lipoprotein cholesterol (LDL C) might increase the motivation for patients to be persistent. We investigated whether the baseline LDL-C value influences the discontinuation of statin treatment in patients with and without previous CV events. METHODS: A cohort study was performed using information from the Swedish national registers concerning dispensed drugs, hospital contacts, cause of death, and socioeconomic status, and linked with data from clinical laboratories. Incident statin users 20 years of age or older and starting treatment between 2006 and 2007 were identified and followed for 1 year. Baseline LDL-C level was defined as the last available laboratory test result during 6 months before the index statin dispensing. Cox regression was used to study discontinuation and estimate the effect on persistence of the baseline LDL-C value adjusting for sex, age, income, comorbidity, previous CV events, type of prescriber, and country of birth. Subgroup analyses stratifying by previous CV events and by diagnosis of diabetes among subjects without previous CV events were performed. RESULTS: A total of 29,389 patients were identified; 35.4% had a previous CV event. A high baseline LDL-C value was associated with a lower discontinuation rate (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.72-0.91) in patients without previous CV events. When stratifying further by diabetes diagnosis, the association was confirmed only in patients without diabetes. No association between LDL-C and persistence was found in patients with previous CV events. CONCLUSIONS: High levels of LDL-C were positively associated with statin persistence in newly treated diabetes patients without previous CV events. PMID- 26671241 TI - Historical cases of anthrax in Sweden 1916-1961. AB - As in most European countries, anthrax was common in Swedish livestock during the centuries leading up to the mid-twentieth century. After 1957, the disease was regarded as practically extinct. However, in the past 7 years, three outbreaks have caused public alarm because of the risk of environmental contamination. Properly buried carcasses should present little risk of spore contamination, and instructions were in place to ensure this since the 1890s. However, as has been demonstrated in recent outbreaks, carcasses were not always adequately buried and viable spores may remain in some sites. This study was prompted by the lack of historical information to assess the geographical risk of old anthrax spores. The aim was to obtain sufficient information to map old anthrax outbreaks, to study clusters and variation between years. Historical data were retrieved from Official National and Regional Veterinary Archives. In the years 1916 to 1961, anthrax was reported from more than 3000 farms and all 24 counties in Sweden were affected. Most cases were single animals, but there were also some larger outbreaks mainly involving cattle. Anthrax in horses was mostly reported before the mid-twentieth century, and the same was seen for pigs and wildlife. A ban in 1957, on the import of bone meal for animal feed led to a drastic reduction of outbreaks. The majority of cases were reported during the summer months in animals on pasture. Historical records proved useful for the investigation of current outbreaks. If handled properly, old carcasses pose no substantial risk, but if not, they may present a risk to grazing animals in some areas. Historical information is useful for all planning of work that involves digging or relocation of soil masses. Anthrax can be regarded as one of the diseases where history is a key to present knowledge. PMID- 26671242 TI - The Impact of Head Start Enrollment Duration on Migrant Children's Health Outcomes. AB - The purpose of this study is to examine whether family characteristics and the length of children's enrollment in Migrant Head Start affects children's health treatment. Children in the Michigan Migrant Head Start were classified depending on years of enrollments: One year (n = 638), two years (n = 293), and three or more years (n = 426). Logistic regression analyses were conducted to examine whether the probability of children receiving health treatment differed depending on years of enrollment. There is a higher health treatment rate among children who attended Head Start for multiple years than for those who attended for one year. Children's special needs status, of siblings, ethnicity, parental educational level, and marital status were related to preventative dental and physical health treatment outcomes. Although the primary goal of Head Start is school readiness rather than health improvement, migrant and seasonal farmworker children are likely to receive more health treatment if they attend more years of comprehensive intervention, such as Head Start, for positive physical and dental health. PMID- 26671243 TI - Informal Financial Assistance for Patients With a Hematological Malignancy: Implications for Oncology Social Work Practice. AB - The article presents original research findings on informal financial assistance for hematological patients; that is, the gifts from family, friends, and communities that help patients cope with the financial hardship associated with cancer. The qualitative study involved interviews with 45 hematology patients that were audio-recorded, transcribed, coded, and then thematically analyzed. The findings examine the differing perspectives that individuals and families bring to the notion of informal financial aid, provide examples of individuals who require and receive informal financial assistance, and conclude with descriptions of those who require informal financial assistance but it is not available. The implications of the findings for oncology social work practice are explored. PMID- 26671244 TI - Integrated and Culturally Relevant Care: A Model to Prepare Social Workers for Primary Care Behavioral Health Practice. AB - Policymakers and researchers emphasize needs for an integrated, effective, and efficient health care system to address well-documented disparities and inequities in care experienced by diverse populations. The Affordable Care Act, through its support of integrated health care, addresses social determinants of health with a goal of increasing access to care. Social work is poised to assume a central position in health care reform and integrated behavioral health, but must prepare practitioners to work alongside medical providers in health care settings. This article describes a social work field education model developed in partnership with community mental health and health care providers. The model, Integrated and Culturally Relevant Care, prepares social work students to provide behavioral health services in integrated primary care environments. PMID- 26671245 TI - Predictors of Self and Surrogate Online Health Information Seeking in Family Caregivers to Cancer Survivors. AB - The purpose of this research is to investigate various factors predicting online health information seeking for themselves (self OHIS) and online health information seeking for others (surrogate OHIS) in family caregivers to cancer survivors. To address this purpose, this study applies the comprehensive model of information seeking as a theoretical framework for explaining the relationships between various predictors and two types of OHIS. The data used in this study were taken from the Health Information National Trends Survey 4. A total of 1,113 family caregivers were included in this study. Logistic regression analyses were conducted to examine the effects of predictors on Internet use for health information seeking. Caregivers' self and surrogate OHIS were commonly predicted by their self-rated health and attention to the Internet. However, age, race, and education were significantly associated with self OHIS only, while gender and marital status were significantly associated with surrogate OHIS only. These results suggest that family caregivers' self and surrogate OHIS are predicted by common factors, as well as predicted by different specific factors. PMID- 26671248 TI - Multiple Simultaneous Spontaneous Intracerebral Hemorrhages: A Rare Entity. AB - BACKGROUND: In hospital databases, multiple simultaneous spontaneous intracerebral hemorrhages (ICH-m) account for 0.7-5.6% of all ICHs. Their long term outcome has never been systematically and prospectively investigated. We aimed at identifying the long-term outcome of patients with ICH-m. METHODS: We prospectively recruited consecutive adults with ICH-m and followed them up for at least 4.5 years. We classified patients into the following 3 groups: (i) definite or probable cerebral amyloid angiopathy (CAA), (ii) deep perforating vasculopathy (DPV) and (iii) unknown causes. RESULTS: Of 562 consecutive patients with ICH, 32 had ICH-m (5.7%): 8 (25%) with probable CAA, 5 (16%) with DPV and 19 (59%) with ICH-m of undetermined cause. At the last visit (cumulative follow-up of 39.5 person-year), 27 patients (84%) had died, and 3 of the 5 survivors were independent. Late-onset seizures, recurrent ICH-m (symptomatic or not) and new brain microbleeds were mainly found in patients with probable CAA. CONCLUSIONS: ICH-m is a rare but extremely severe expression of ICH. Survivors with CAA are more likely to develop late seizures and new hemorrhagic lesions. Because of low survival rates, large multicenter cohort studies are needed for a better understanding of this rare condition. PMID- 26671247 TI - Divergent Reactivity of Amino Acid Alkyl Ester Hydrochlorides with 2 Oxoaldehydes: Role of Selenium Dioxide To Promote Regioselective Synthesis of Imidazoles. AB - Novel amino acid substituted imidazoles engendered from amino acid alkyl ester hydrochlorides and 2-oxoaldehydes as a result of selenium dioxide promoted unconventional reaction in a basic environment is presented for the first time. Despite the nature of the 2-oxoaldehydes/amino acids used, the imidazoles generated had a functional core structure, and all of the reactions meticulously retained regioselectivity. The imperative feature of these reactions was the uniqueness of selenium dioxide in fixing two nitrogen atoms from amino acids through an in situ generated ArCOCHN1N2 system. PMID- 26671249 TI - Label-free colorimetric detection of biological thiols based on target-triggered inhibition of photoinduced formation of AuNPs. AB - A label-free colorimetric method for the detection of biological thiols (biothiols) was developed. This method is based on prevention of the photoinduced reduction of auric ions (Au(III)) in the presence of amino acids (acting as a reducing agent) by biothiols; the photoinduced reduction is inhibited due to the strong interaction of the biothiols with Au(III). In this method, the sample was first incubated in an assay solution containing Au(III) and threonine; the sample solution was then exposed to 254 nm UV light. For samples without biothiols, this process led to the photoreduction of Au(III) followed by growth of gold nanoparticles accompanied by the visually detectable development of a red coloration typified by an absorption peak at ca 530 nm. Conversely, in the presence of biothiols, reduction of Au(III) to Au(0) was prevented by entrapment of Au(III) within the biothiols via the thiol group. The solution thus remained colorless even after UV irradiation, which was used as an indicator of the presence of biothiols. Using this strategy, biothiols were very conveniently analyzed by monitoring color changes of the samples with the naked eye or a UV vis spectrometer. The strategy based on this interesting phenomenon exhibited high selectivity toward biothiols over common amino acids and was successfully employed for reliable quantification of biothiols present in human plasma, demonstrating its great potential for clinical applications. PMID- 26671250 TI - Determinants of Obesity in Italian Adults: The Role of Taste Sensitivity, Food Liking, and Food Neophobia. AB - Recent evidence has suggested that factors related to sensory perception may explain excess weight. The objective of this study was to consider multiple aspects while investigating the phenomenon of obesity. One goal was to compare taste acuity (taste threshold and density of fungiform papillae) in both normal weight and obese subjects. Thresholds for 4 basic tastes and the fat stimulus were investigated. A second research goal was to study the relationship between food neophobia and food liking according to the body mass index and taste sensitivity. The results showed that obese subjects seem to have higher threshold values and a reduced number of fungiform papillae than do normal weight subjects. Food neophobia did not vary with nutritional status, whereas differences were found for food liking, with obese subjects showing significantly higher liking ratings for high energy dense products compared with normal weight subjects. PMID- 26671251 TI - Epileptic seizure in a patient with an implantable cardioverter-defibrillator: Quo vadis right ventricular lead? AB - The case of a 77-year-old man admitted for suspected epileptic seizure is reported. Patient history showed implantation of a single-chamber implantable cardioverter-defibrillator (ICD) after cardiac arrest in 2007 with replacement in 2012 due to battery depletion; the patient reported no previous syncope, unconsciousness or seizures. Interrogation records of the ICD showed five ventricular tachyarrhythmia episodes that corresponded to the "seizure". Further examination revealed incorrect position of the RV-lead. Diagnosis was a provoked epileptic seizure due to undersensing of ventricular tachycardia because of improper ICD lead implantation in the coronary sinus. Treatment consisted of implantation of a new device with an additional ICD lead into the right ventricle. PMID- 26671253 TI - The microwave-assisted ortho-alkylation of azine N-oxides with N-tosylhydrazones catalyzed by copper(I) iodide. AB - A copper catalyzed regioselective cross-coupling of N-tosylhydrazones with azine N-oxides to yield ortho-alkylated products in moderate to good yields is reported. The reaction is facilitated by microwave, takes place without any ligand, and uses inexpensive copper(I) iodide as the catalyst. PMID- 26671252 TI - [Acute kidney injury and renal replacement therapy in victims from out-of hospital cardiac arrest with administration of contrast agent]. AB - BACKGROUND: Early coronary angiography and computed tomography are recommended in survivors of out-of-hospital cardiac arrest (OHCA). However, both techniques require iodinated contrast agent although the effects on incident acute kidney injury are unknown. The aim of this study was to explore the incidence of acute kidney injuries (AKI) and need for renal replacement therapy (RRT) in patients after nontraumatic OHCA with special regard to the administration of contrast agent during the early in-hospital diagnostic workup. MATERIALS AND METHODS: Data from all survivors of OHCA admitted to our hospital between 1 January 2008 and 30 June 2015 were retrospectively collected. Incidence of AKI and RRT between the contrast and no contrast groups were compared. RESULTS: Of 280 OHCA survivors, 133 (47.5 %) received contrast agent (227.0 +/- 136.5 ml). Within 72 h after hospital admission, 47 of 129 survivors (36.4 %) developed AKI of any stage, but AKI was more common in patients without early contrast administration than in patients with early contrast administration (54.5 vs. 28.2 %; p = 0.011). Patients who survived until hospital discharge had higher serum creatinine levels at admission than at hospital discharge (1.17 +/- 0.37 vs. 0.92 +/- 0.35; p < 0.001). CONCLUSION: AKI is common in survivors of OHCA, and RRT following OHCA is needed more frequently than in other cardiac disease. Despite elevated serum creatinine levels at admission, we could not show an association between early contrast administration in survivors of OHCA and AKI incidence. PMID- 26671254 TI - A theoretical framework for human and veterinary medical ethics education. AB - In their practice, physicians and veterinarians need to resort to an array of ethical competences. As a teaching topic, however, there is no accepted gold standard for human medical ethics, and veterinary medical ethics is not yet well established. This paper provides a reflection on the underlying aims of human and veterinary medical ethics education. Drawing from published literature on ethics education in the health professions a theoretical framework common to the teaching of human and veterinary medical ethics is proposed, based on three concepts: professional rules, moral virtues and ethical skills. The rules approach relies on the transmission of professional and social values by means of regulatory documents and depends intimately on the knowledge that students have of those documents. The virtues approach involves the inculcation of moral values and virtues that will stimulate students to develop desirable behaviours. The main focus of this approach to ethics is to develop students' attitudinal competences. Finally, the skills approach is focused on equipping the students with the necessary moral reasoning abilities to recognise and respect the plurality of ethical views that make part of contemporary society. This framework can inform future curriculum development in human and veterinary medical ethics as well as in other health care professions. PMID- 26671255 TI - Massive intracellular gene transfer during plastid genome reduction in nongreen Orobanchaceae. AB - Plastid genomes (plastomes) of nonphotosynthetic plants experience extensive gene losses and an acceleration of molecular evolutionary rates. Here, we inferred the mechanisms and timing of reductive genome evolution under relaxed selection in the broomrape family (Orobanchaceae). We analyzed the plastomes of several parasites with a major focus on the genus Orobanche using genome-descriptive and Bayesian phylogenetic-comparative methods. Besides this, we scanned the parasites' other cellular genomes to trace the fate of all genes that were purged from their plastomes. Our analyses indicate that the first functional gene losses occurred within 10 Myr of the transition to obligate parasitism in Orobanchaceae, and that the physical plastome reduction proceeds by small deletions that accumulate over time. Evolutionary rate shifts coincide with the genomic reduction process in broomrapes, suggesting that the shift of selectional constraints away from photosynthesis to other molecular processes alters the plastid rate equilibrium. Most of the photosynthesis-related genes or fragments of genes lost from the plastomes of broomrapes have survived in their nuclear or mitochondrial genomes as the results of multiple intracellular transfers and subsequent fragmentation. Our findings indicate that nonessential DNA is eliminated much faster in the plastomes of nonphotosynthetic parasites than in their other cellular genomes. PMID- 26671257 TI - Erratum to: CO2 Biofixation by the Cyanobacterium Spirulina sp. LEB 18 and the Green Alga Chlorella fusca LEB 111 Grown Using Gas Effluents and Solid Residues of Thermoelectric Origin. PMID- 26671258 TI - Synthesis, Crystal Structure, and Magnetic Properties of a Chiral Cyanide-Bridged Bimetallic Framework K3[Mn(II)(L-asp)]6[Cr(III)(CN)6].2H2O. AB - All five coordinating atoms of the amino-acid dianion L-aspartate (L-asp = NH2CH(COO)CH2COO(2-)) are found to be involved in coordination with Mn(II) in the presence of [Cr(III)(CN)6](3-) to self-assemble into a chiral three-dimensional cyanide-bridged K3[Mn(L-asp)]6[Cr(CN)6].2H2O containing the highest ratio of Mn:Cr of 6:1. It adopts the chiral P3 (no. 143) space group consisting of zigzag Mn-OCO-Mn chains sharing edges of hexagonal channels with central [Cr(CN)6](3-), while K(+) and H2O occupy another parallel star-shaped channel. Its magnetic susceptibility above 100 K is dominated by the nearest neighbor (Mn-Cr at 5.08 and 5.31 A) antiferromagnetic (AF) exchange interactions (theta = -15(1) K) and below 40 K by further AF interaction between Mn and Mn at 5.32 A. It finally reaches a steady value at 4.5 K, where a bifurcation of the zero-field-cooled and field-cooled magnetizations is observed in small fields (<1 kOe). The isothermal magnetization is linear in field and deviating toward saturation above 60 kOe at 2 K. No imaginary component of the ac susceptibilities is observed. This behavior is associated with long-range antiferromagnetic order of a helical or conic nature where the magnetic sublattices are numerous [2n * (6Mn + 1Cr)], leading to a domain of sufficient size to allow for the presence of the bifurcation. A model is proposed based on the local anisotropy and symmetry multiplicity of the space group. PMID- 26671256 TI - Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family. AB - The Neisseriaceae family of bacteria causes a range of diseases including meningitis, septicaemia, gonorrhoea and endocarditis, and extracts haem from haemoglobin as an important iron source within the iron-limited environment of its human host. Herein we report crystal structures of apo- and haemoglobin-bound HpuA, an essential component of this haem import system. The interface involves long loops on the bacterial receptor that present hydrophobic side chains for packing against the surface of haemoglobin. Interestingly, our structural and biochemical analyses of Kingella denitrificans and Neisseria gonorrhoeae HpuA mutants, although validating the interactions observed in the crystal structure, show how Neisseriaceae have the fascinating ability to diversify functional sequences and yet retain the haemoglobin binding function. Our results present the first description of HpuA's role in direct binding of haemoglobin. PMID- 26671259 TI - Limitation in monitoring depth of anesthesia: a case report. AB - Although we describe a clinical situation that most likely occurs in hundreds of operatory rooms in the world, we report this case as provocation. It concerns an unexpected awakening from an appropriate depth of anesthesia, although the BIS monitor showed a BIS index of less than 50 for a prolonged period before and after the event. Approximately 30 min after induction of anesthesia, the patient had a hypothetic sudden arousal of consciousness, with spontaneous movements, facial muscle activation, intolerance to the tracheal tube, and tearing. After immediate intravenous administration of midazolam (4 mg), the patient returned to a depth of anesthesia status, and surgery was completed uneventfully. The patient had no recall of the event when questioned during the episode, at emergence, or at 24 h, 36 h, and 7 days after surgery. Were these events spinal reflexes to pain or stimulation although the cortex was still anesthetized? Maybe this is the more rational explanation. Was the patient awake but not aware? Is it possible that our patient experienced only a transient arousal from consciousness, and that he did not have recall because the arousal time was short and we blocked memory consolidation? The latter hypothesis provides an opportunity to discuss the evidence that at the moment there is no device to assess the depth of anesthesia. We also focus on the possibility of interfering with memory processing under anesthesia. PMID- 26671261 TI - Utility of x-plane TEE imaging in giant right atrial myxoma. PMID- 26671260 TI - Simulation-based airway management training: application and looking forward. AB - Within the airway management field, simulation has been used as a tool of training for over 40 years. Simulation training offers a chance of active involvement for the trainees. It can effectively enhance and upgrade the knowledge and skills of the trainees in airway management, and subsequently decrease medical errors and improve patients' outcomes and safety through a variety of airway management training modalities, such as common airway skills, difficult airway management strategies, and crisis management skills. To perform simulation-based airway management training effectively, not only are task trainers and high-fidelity simulators required but also instructors with rich experience in airway management simulation training and optimal curriculum design are essential. PMID- 26671262 TI - Helicopter emergency medical services for adults with major trauma. AB - BACKGROUND: Although helicopters are presently an integral part of trauma systems in most developed nations, previous reviews and studies to date have raised questions about which groups of traumatically injured people derive the greatest benefit. OBJECTIVES: To determine if helicopter emergency medical services (HEMS) transport, compared with ground emergency medical services (GEMS) transport, is associated with improved morbidity and mortality for adults with major trauma. SEARCH METHODS: We ran the most recent search on 29 April 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library (Cochrane Central Register of Controlled Trials; CENTRAL), MEDLINE (OvidSP), EMBASE Classic + EMBASE (OvidSP), CINAHL Plus (EBSCOhost), four other sources, and clinical trials registers. We screened reference lists. SELECTION CRITERIA: Eligible trials included randomized controlled trials (RCTs) and nonrandomized intervention studies. We also evaluated nonrandomized studies (NRS), including controlled trials and cohort studies. Each study was required to have a GEMS comparison group. An Injury Severity Score (ISS) of at least 15 or an equivalent marker for injury severity was required. We included adults age 16 years or older. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed the risk of bias of included studies. We applied the Downs and Black quality assessment tool for NRS. We analyzed the results in a narrative review, and with studies grouped by methodology and injury type. We constructed 'Summary of findings' tables in accordance with the GRADE Working Group criteria. MAIN RESULTS: This review includes 38 studies, of which 34 studies examined survival following transportation by HEMS compared with GEMS for adults with major trauma. Four studies were of inter-facility transfer to a higher level trauma center by HEMS compared with GEMS. All studies were NRS; we found no RCTs. The primary outcome was survival at hospital discharge. We calculated unadjusted mortality using data from 282,258 people from 28 of the 38 studies included in the primary analysis. Overall, there was considerable heterogeneity and we could not determine an accurate estimate of overall effect.Based on the unadjusted mortality data from six trials that focused on traumatic brain injury, there was no decreased risk of death with HEMS. Twenty-one studies used multivariate regression to adjust for confounding. Results varied, some studies found a benefit of HEMS while others did not. Trauma-Related Injury Severity Score (TRISS)-based analysis methods were used in 14 studies; studies showed survival benefits in both the HEMS and GEMS groups as compared with MTOS. We found no studies evaluating the secondary outcome, morbidity, as assessed by quality adjusted life years (QALYs) and disability-adjusted life years (DALYs). Four studies suggested a small to moderate benefit when HEMS was used to transfer people to higher level trauma centers. Road traffic and helicopter crashes are adverse effects which can occur with either method of transport. Data regarding safety were not available in any of the included studies. Overall, the quality of the included studies was very low as assessed by the GRADE Working Group criteria. AUTHORS' CONCLUSIONS: Due to the methodological weakness of the available literature, and the considerable heterogeneity of effects and study methodologies, we could not determine an accurate composite estimate of the benefit of HEMS. Although some of the 19 multivariate regression studies indicated improved survival associated with HEMS, others did not. This was also the case for the TRISS-based studies. All were subject to a low quality of evidence as assessed by the GRADE Working Group criteria due to their nonrandomized design. The question of which elements of HEMS may be beneficial has not been fully answered. The results from this review provide motivation for future work in this area. This includes an ongoing need for diligent reporting of research methods, which is imperative for transparency and to maximize the potential utility of results. Large, multicenter studies are warranted as these will help produce more robust estimates of treatment effects. Future work in this area should also examine the costs and safety of HEMS, since multiple contextual determinants must be considered when evaluating the effects of HEMS for adults with major trauma. PMID- 26671263 TI - Structural Control of Cell Permeability with Highly Emissive Europium(III) Complexes Permits Different Microscopy Applications. AB - Four anionic europium complexes are described based on triazacyclononane tris carboxylate or phosphinate ligands. In each case, the three sensitising chromophores comprise a substituted aryl-alkynyl pyridine group, with complex brightness in water falling in the range 4 to 23 mM(-1) cm(-1) . para Substitution of the aryl ring with carboxymethyl groups gives complexes that are taken into cells, stain the lysosomes selectively and unexpectedly permit lifetime measurements of lysosomal pH. In contrast, the introduction of sulfonate groups inhibits cell uptake enabling the Eu complex to be used as an extracellular donor for FRET applications at the membrane surface. Using time gated FRET microscopy, the cell membrane structure was highlighted, in which Cell Mask Deep Red was used as a membrane- localized FRET acceptor. PMID- 26671264 TI - Synthesis of Unsymmetrical alpha,alpha-Diarylacetates. AB - Ethyl bromofluoroacetate has been developed as a precursor for the convenient synthesis of unsymmetrical alpha,alpha-diarylacetates featuring indoles, anilines, and other electron-rich aromatics. In conjunction with a mild Lewis acid catalyzed C-N -> C-C exchange, intermediate arylglycines can be synthesized and transformed into alpha,alpha-diarylacetates in a one-pot protocol, resulting in a net diarylation reaction exhibiting a wide scope. In the context of diarylacetates, the synthetic equivalence of the fluorinated reagent with alpha nitro-alpha-diazo carbonyls was established. PMID- 26671265 TI - Experimenting with sex: four approaches to the genetics of sex reversal before 1950. AB - In the early twentieth century, Tatsuo Aida in Japan, Ojvind Winge in Denmark, Richard Goldschmidt in Germany, and Calvin Bridges in the United States all developed different experimental systems to study the genetics of sex reversal. These locally specific experimental systems grounded these experimenters' understanding of sex reversal as well as their interpretation of claims regarding experimental results and theories. The comparison of four researchers and their experimental systems reveals how those different systems mediated their understanding of genetic phenomena, and influenced their interpretations of sex reversal. PMID- 26671267 TI - Bugs and Drugs: Time for Action. PMID- 26671268 TI - The Changing Landscape of Consultant Pharmacy Part 1 of 2. AB - A dramatic increase in the senior population, along with adjustments in reimbursement for health care services, is altering the landscape of consultant or senior care pharmacy. An increased focus on quality, rather than quantity of services, offers new opportunities and challenges for pharmacists and all members of the health care team. This article features the viewpoints of three leaders in senior care pharmacy, and their visions for the future of this dynamic profession. PMID- 26671266 TI - Autophagy-mediated longevity is modulated by lipoprotein biogenesis. AB - Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID- 26671269 TI - Ceftazidime/Avibactam: A New Antibiotic for Gram-Negative Infections. AB - OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosing, and administration of ceftazidime/avibactam (CAZ/AVI). DATA SOURCES: A search of PubMed using the terms "ceftazidime," "avibactam," "NXL104," and "AVE1330A" was performed. The manufacturer's website was also reviewed to further identify relevant information. STUDY SELECTION: All English-language articles from 2004 to May 2015 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. DATA SYNTHESIS: CAZ/AVI is a new cephalosporin beta lactamase inhibitor combination with a spectrum of activity targeted against Gram negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa. The dosing regimen is 2.5 g every eight hours administered via IV infusion over two hours for 5 to 14 days. The dosing regimen should be adjusted based on renal function. A phase II trial has demonstrated that clinical cure rates with CAZ/AVI plus metronidazole are comparable to those with meropenem in the treatment of adults with complicated intra-abdominal infections. Another phase II clinical trial has demonstrated that clinical cure rates with CAZ/AVI are comparable to those with imipenem/cilastatin for the treatment of adults with complicated urinary tract infections (cUTIs). CAZ/AVI has a side effect profile similar to that of cephalosporins and carbapenems. CONCLUSION: CAZ/AVI has a favorable efficacy and safety profile in the treatment of adults with complicated intra abdominal infections or cUTIs. Further research is needed to refine its role, particularly for the treatment of multi-drug-resistant Gram-negative infections. PMID- 26671270 TI - Potential Cross-Reactivity Between Penicillin Derivatives and Cephalosporins. AB - Allergic reactions to both penicillins and cephalosporins are relatively common. Patients who have had a previous allergic reaction to a penicillin derivative may also be prone to a further reaction if treated with cephalosporins. This case illustrates several important points about potential cross-reactivity between penicillin derivatives and cephalosporins, as well as the benefits of an extended hours pharmacy service in a longterm care facility. PMID- 26671271 TI - Managing Medication Adherence in Elderly Hypertensive Patients Through Pharmacist Home Visits. AB - OBJECTIVE: The purpose of the Managing Your Blood Pressure program was to reduce health disparities in blood pressure (BP) control by improving medication adherence in a cohort of geriatric African-Americans with hypertension (HTN). DESIGN: The program was implemented using a quasi-experimental pre- and postintervention study design that utilized a pharmacist home-based model and follow-up educational phone calls to impact BP over a six-month period. SETTING: Home visits occurred in participants' residences, and phone calls occurred at program headquarters at Texas Southern University (Houston, Texas). MAIN OUTCOME MEASURES: The primary outcome measure was BP control rate, and secondary outcome measures were knowledge of HTN, medication adherence, and use of a BP monitor. RESULTS: At six months, 306 of the 431 patients recruited completed all phases of the program (two in-home consultations and biweekly telephone consultations). At the end of the six-month intervention period, the reduction in mean systolic BP was statistically significant (baseline 140 mmHg vs. six months 137 mmHg; P < 0.049). No difference in mean diastolic BP pre- and postintervention was found. The percent of patients with controlled BP improved from 46.7% to 49.5%; P = 0.34. Medication adherence, self-monitoring of BP, and knowledge of HTN were significantly improved from baseline to postintervention. CONCLUSION: Pharmacist led interventions in the home were effective in improving BP control and medication adherence. Further programs are needed to address uncontrolled HTN in this vulnerable population. PMID- 26671272 TI - A Pilot Study to Evaluate Effectiveness of INR Self-Testing in Elderly Patients. AB - OBJECTIVE: To determine if international normalized ratio (INR) patient self testing (PST) resulted in an increased time in therapeutic range (TTR) in an elderly population when compared with clinic testing over a six-month period. DESIGN: A pilot study and retrospective chart review from August 2010 to August 2014. SETTING: Ambulatory, anticoagulation clinic with two locations in Sun City West and Peoria, Arizona. PARTICIPANTS: Of 91 patients, the data of 20 patients who were 65 years of age or older and had at least six months of pre- and post PST INR data were extracted and analyzed. OUTCOMES: The primary outcome evaluated improvement of TTR during post-PST in elderly patients compared with clinic management over a six-month period. Secondary outcomes assessed patients' satisfaction with PST and identified barriers to PST. RESULTS: The post-PST mean TTR significantly increased to 73% from 63.6% for the first six months of PST (P = 0.04). Participants were satisfied with PST, with an average score ranging from 4.6 to 5 on a Likert scale of 1 to 5 on 10 satisfaction survey questions. Cost was identified as the most common barrier to PST, with 43% of patients not participating in PST because of financial burden. CONCLUSION: With appropriate screening and training, PST is associated with improved TTRs and higher patient satisfaction in elderly patients when compared with clinic testing. Barriers identified to PST include cost, the complex process, and noncompliance. PMID- 26671274 TI - Effect of parathyroid hormone on serum magnesium levels: the neglected relationship in hemodialysis patients with secondary hyperparathyroidism. AB - Chronic kidney disease-mineral and bone disorder (CKD-MBD) is an important complication in patients with end-stage renal disease. Since recent studies have shown that magnesium (Mg) disturbance plays an important role in CKD-MBD and cardiovascular mortality, the interest on magnesium has grown recently. Although much concern focused on the effect of Mg on parathyroid hormone (PTH) levels, however, the influence of PTH on serum Mg levels is nearly unexplored. To evaluate the effect of PTH on serum Mg levels, we first described the relationship between serum Mg and PTH in secondary hyperparathyroidism. Besides, we also monitored the changes of serum Mg concentration after parathyroidectomy (PTX) in 23 patients. In our study, we found that hypermagnesemia (>2.5 mg/dL) occurred in up to 44% of cases and hypomagnesemia did not present. No statistically significant correlations were found between serum Mg levels and PTH (r = -0.143, p = 0.134). Correlation analysis and regression analysis suggested that the derangement of magnesium homeostasis was consistent with the derangement of calcium/phosphorus homeostasis. However, after PTX, serum magnesium levels dropped immediately after the surgery, minimally at the first day and gradually restored from the third day. The changes of serum Mg after surgery was positive correlated with the changes of serum phosphate (r = 0.558, p = 0.003). Taken altogether, our data suggested that the therapeutic strategies to achieve optimum serum magnesium levels in CKD-MBD should take into account the varying stages of disease development since PTH could also influence magnesium metabolism and this problem might be important in severe secondary hyperparathyroidism. PMID- 26671275 TI - Gene selection and cloning approaches for co-expression and production of recombinant protein-protein complexes. AB - Multiprotein complexes play essential roles in all cells and X-ray crystallography can provide unparalleled insight into their structure and function. Many of these complexes are believed to be sufficiently stable for structural biology studies, but the production of protein-protein complexes using recombinant technologies is still labor-intensive. We have explored several strategies for the identification and cloning of heterodimers and heterotrimers that are compatible with the high-throughput (HTP) structural biology pipeline developed for single proteins. Two approaches are presented and compared which resulted in co-expression of paired genes from a single expression vector. Native operons encoding predicted interacting proteins were selected from a repertoire of genomes, and cloned directly to expression vector. In an alternative approach, Helicobacter pylori proteins predicted to interact strongly were cloned, each associated with translational control elements, then linked into an artificial operon. Proteins were then expressed and purified by standard HTP protocols, resulting to date in the structure determination of two H. pylori complexes. PMID- 26671276 TI - MR imaging of ovarian masses: classification and differential diagnosis. AB - OBJECTIVE: We propose a Magnetic Resonance Imaging (MRI) guided approach to differential diagnosis of ovarian tumours based on morphological appearance. BACKGROUND: Characterization of ovarian lesions is of great importance in order to plan adequate therapeutic procedures, and may influence patient's management. Optimal assessment of adnexal masses requires a multidisciplinary approach, based on physical examination, laboratory tests and imaging techniques. Primary ovarian tumours can be classified into three main categories according to tumour origin: epithelial, germ cell and sex cord-stromal tumours. Ovarian neoplasms may be benign, borderline or malignant. Using an imaging-guided approach based on morphological appearance, we classified adnexal masses into four main groups: unilocular cyst, multilocular cyst, cystic and solid, predominantly solid. We describe MR signal intensity features and enhancement behaviour of ovarian lesions using pathologically proven examples from our institution. CONCLUSION: MRI is an essential problem-solving tool to determine the site of origin of a pelvic mass, to characterize an adnexal mass, and to detect local invasion. The main advantages of MRI are the high contrast resolution and lack of ionizing radiation exposure. Although different pathological conditions may show similar radiologic manifestations, radiologists should be aware of MRI features of ovarian lesions that may orientate differential diagnosis. TEACHING POINTS: * Diagnostic imaging plays a crucial role in detection, characterization and staging of adnexal masses. * Characterization of an ovarian lesion may influence patient's management. * Different pathological conditions may have similar radiologic manifestations. * Non-neoplastic lesions should always be taken into consideration. PMID- 26671278 TI - Current controversies in prenatal diagnosis 4: preimplantation genetic screening should be routinely offered to all preimplantation genetic diagnosis cases. PMID- 26671277 TI - Analysis of Pirlimycin Residues in Beef Muscle, Milk, and Honey by a Biotin Streptavidin-Amplified Enzyme-Linked Immunosorbent Assay. AB - Food contamination by veterinary drug residues is a worldwide public health concern and requires continuous monitoring. In this study, we developed a biotin streptavidin-amplified ELISA (BA-ELISA) using a produced monoclonal antibody for detecting pirlimycin residues in beef muscle, milk, and honey. The IC50 value of the BA-ELISA was 1.6 ng/mL for pirlimycin in buffer, and the sensitivity was improved 3 times compared to traditional ELISAs. The optimized BA-ELISA can be used to quantitate trace amounts of pirlimycin residues in beef muscle, milk, and honey. This method had limits of detection (LODs) of 4.45 MUg/kg in beef muscle, 1.65 MUg/L in milk, and 2.75 MUg/kg in honey. The average recovery of the BA ELISA ranged from 78 to 97%, and the coefficient of variation ranged from 5.3 to 13.5%. The developed BA-ELISA method was validated using LC-MS/MS, and the BA ELISA can be used for routine screening analysis of pirlimycin residues. PMID- 26671279 TI - Unmet Information Needs of Low-Risk Thyroid Cancer Survivors. PMID- 26671280 TI - Long-Term Exposure to High Altitude Affects Conflict Control in the Conflict Resolving Stage. AB - The neurocognitive basis of the effect of long-term high altitude exposure on conflict control is unclear. Event related potentials (ERPs) were recorded in a flanker task to investigate the influence of high altitude on conflict control in the high-altitude group (who had lived at high altitude for three years but were born at low altitude) and the low-altitude group (living in low altitude only). Although altitude effect was not significant at the behavioral level, ERPs showed cognitive conflict modulation. The interaction between group and trial type was significant: P3 amplitude was greater in the low-altitude group than in the high altitude group in the incongruent trial. This result suggests that long-term exposure to high altitude affects conflict control in the conflict-resolving stage, and that attentional resources are decreased to resist the conflict control in the high-altitude group. PMID- 26671282 TI - The effect of exercise training on the course of cardiac troponin T and I levels: three independent training studies. AB - With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T (cTnT ) and I (cTnI) were monitored in two resistance-type exercise training programs (12-week (study 1) and 24-week (study 2)) in older adults (>=65 years). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in (pre)frail older adults was performed (study 3). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 (study 1: cTnT -0.13 (-0.33-+0.08) ng/L/12-weeks, cTnI -0.10 (-0.33-+0.12) ng/L/12-weeks; study 2: cTnT -1.99 (-4.79 +0.81) ng/L/24-weeks, cTnI -1.59 (-5.70-+2.51) ng/L/24-weeks). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 (p = 0.27). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels. PMID- 26671283 TI - Coupling of Thalamocortical Sleep Oscillations Are Important for Memory Consolidation in Humans. AB - Sleep, specifically non-rapid eye movement (NREM) sleep, is thought to play a critical role in the consolidation of recent memories. Two main oscillatory activities observed during NREM, cortical slow oscillations (SO, 0.5-1.0 Hz) and thalamic spindles (12-15 Hz), have been shown to independently correlate with memory improvement. Yet, it is not known how these thalamocortical events interact, or the significance of this interaction, during the consolidation process. Here, we found that systemic administration of the GABAergic drug (zolpidem) increased both the phase-amplitude coupling between SO and spindles, and verbal memory improvement in humans. These results suggest that thalamic spindles that occur during transitions to the cortical SO Up state are optimal for memory consolidation. Our study predicts that the timely interactions between cortical and thalamic events during consolidation, contribute to memory improvement and is mediated by the level of inhibitory neurotransmission. PMID- 26671281 TI - Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy. AB - B7-2(-/-) non-obese diabetic (NOD) mice develop a spontaneous autoimmune polyneuropathy (SAP) that mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, we focused on the role of regulatory T cells (Tregs ) and regulatory B cells (Bregs ) in SAP. We found that deletion of B7-2 in female NOD mice led to a lower frequency and number of Tregs and Bregs in spleens and lymph nodes. Tregs but not Bregs suppressed antigen-stimulated splenocyte proliferation, whereas Bregs inhibited the T helper type 1 (Th1) cytokine response. Both Tregs and Bregs induced an increase in CD4(+) interleukin (IL)-10(+) cells, although less effectively in the absence of B7-2. Adoptive transfer studies revealed that Tregs , but not Bregs , suppressed SAP, while Bregs attenuated disease severity when given prior to symptom onset. B cell deficiency in B cell-deficient (muMT)/B7-2(-/-) NOD mice prevented the development of SAP, which would indicate that the pathogenic role of B cells predominates over its regulatory role in this model. We conclude that Bregs and Tregs control the immunopathogenesis and progression of SAP in a non redundant fashion, and that therapies aimed at expansion of Bregs and Tregs may be an effective approach in autoimmune neuropathies. PMID- 26671284 TI - Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy. AB - Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multicenter, pre-clinical drug and circulating biomarker screening consortium for the field of traumatic brain injury (TBI). In this article, we synthesize the findings from the first five therapies tested by OBTT and discuss both the current work that is ongoing and potential future directions. Based on the results generated from the first five therapies tested within the exacting approach used by OBTT, four (nicotinamide, erythropoietin, cyclosporine A, and simvastatin) performed below or well below what was expected based on the published literature. OBTT has identified, however, the early post-TBI administration of levetiracetam as a promising agent and has advanced it to a gyrencephalic large animal model--fluid percussion injury in micropigs. The sixth and seventh therapies have just completed testing (glibenclamide and Kollidon VA 64), and an eighth drug (AER 271) is in testing. Incorporation of circulating brain injury biomarker assessments into these pre-clinical studies suggests considerable potential for diagnostic and theranostic utility of glial fibrillary acidic protein in pre-clinical studies. Given the failures in clinical translation of therapies in TBI, rigorous multicenter, pre-clinical approaches to therapeutic screening such as OBTT may be important for the ultimate translation of therapies to the human condition. PMID- 26671285 TI - Effects of a medical emergency team follow-up programme on patients discharged from the medical intensive care unit to the general ward: a single-centre experience. AB - RATIONALE, AIMS AND OBJECTIVES: The aim of this study was to analyse the effects of the follow-up programme implemented by the Asan Medical Center Medical Emergency Team (MET). METHOD: A quasi-experimental pre-post intervention design was used, retrospectively reviewed. The follow-up programme includes respiratory care, regular visits and communication between the attending doctors and MET nurse for patients discharged from the medical intensive care unit (MICU) to the general ward. This programme has been implemented since February 2013. Outcomes of patients before and at 1 year after the introduction of the programme were retrospectively reviewed. RESULTS: A total of 1229 patients were enrolled and divided two groups (Before, n = 624; After the introduction of the programme, n = 625). Forty-six patients (3.7%) were readmitted to the ICU within 72 hours, and there was no significant difference found between the two groups (3.7% versus 3.7%, P = 0.996). Respiratory distress was the most common reason for readmission (67.4%). Cardiac arrest developed in four (0.6%) Before patients; whereas, no cardiac arrest occurred in the After group (0.0%, P = 0.062) cases. A total of 223 patients were discharged to the step-down units. The SOFA (sequential organ failure assessment) score was significantly higher in the step-down unit patients than general ward patients (4.9 +/- 2.8 versus 6.2 +/- 3.1, P = 0.000). In the analysis restricted to patients discharged to step-down units, unplanned ICU readmissions significantly decreased in the After group (9.3% versus 2.6%, P = 0.034). CONCLUSIONS: The implementation of the MET follow-up programme did not change the rate of ICU readmission and cardiac arrest; however, its introduction was associated with the reduced ICU readmission of the high-risk patient populations discharged to the step-down unit. PMID- 26671286 TI - Mechanisms of Reference Frame Selection in Spatial Term Use: Computational and Empirical Studies. AB - Previous studies have shown that multiple reference frames are available and compete for selection during the use of spatial terms such as "above." However, the mechanisms that underlie the selection process are poorly understood. In the current paper we present two experiments and a comparison of three computational models of selection to shed further light on the nature of reference frame selection. The three models are drawn from different areas of human cognition, and we assess whether they may be applied to a reference frame selection by examining their ability to account for both existing and new empirical data comprising acceptance rates, response times, and response time distributions. These three models are the competitive shunting model (Schultheis, ), the leaky competing accumulator (LCA) model (Usher & McClelland, ), and a lexical selection model (Howard, Nickels, Coltheart, & Cole-Virtue, ). Model simulations show that only the LCA model satisfactorily accounts for the empirical observations. The key properties of this model that seem to drive its success are its bounded linear activation function, its number and type of processing stages, and its use of decay. Uncovering these critical properties has important implications for our understanding not only of spatial term use, in particular, but also of conflict and selection in human cognition more generally. PMID- 26671287 TI - Method for Determining the Activation Energy Distribution Function of Complex Reactions by Sieving and Thermogravimetric Measurements. AB - A method for studying the kinetics of thermal degradation of complex compounds is suggested. Although the method is applicable to any matrix whose grain size can be measured, herein we focus our investigation on thermogravimetric analysis, under a nitrogen atmosphere, of ground soft wheat and ground maize. The thermogravimetric curves reveal that there are two well-distinct jumps of mass loss. They correspond to volatilization, which is in the temperature range 298 433 K, and decomposition regions go from 450 to 1073 K. Thermal degradation is schematized as a reaction in the solid state whose kinetics is analyzed separately in each of the two regions. By means of a sieving analysis different size fractions of the material are separated and studied. A quasi-Newton fitting algorithm is used to obtain the grain size distribution as best fit to experimental data. The individual fractions are thermogravimetrically analyzed for deriving the functional relationship between activation energy of the degradation reactions and the particle size. Such functional relationship turns out to be crucial to evaluate the moments of the activation energy distribution, which is unknown in terms of the distribution calculated by sieve analysis. From the knowledge of moments one can reconstruct the reaction conversion. The method is applied first to the volatilization region, then to the decomposition region. The comparison with the experimental data reveals that the method reproduces the experimental conversion with an accuracy of 5-10% in the volatilization region and of 3-5% in the decomposition region. PMID- 26671288 TI - Twinning of cubic diamond explains reported nanodiamond polymorphs. AB - The unusual physical properties and formation conditions attributed to h-, i-, m , and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and <011> rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin (<121> rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications. PMID- 26671289 TI - Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study. AB - BACKGROUND: Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. METHOD: Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. RESULTS: The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. CONCLUSIONS: The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour. PMID- 26671290 TI - A New Route for High-Purity Organic Materials: High-Pressure-Ramp-Induced Ultrafast Polymerization of 2-(Hydroxyethyl)Methacrylate. AB - The synthesis of highly biocompatible polymers is important for modern biotechnologies and medicine. Here, we report a unique process based on a two step high-pressure ramp (HPR) for the ultrafast and efficient bulk polymerization of 2-(hydroxyethyl)methacrylate (HEMA) at room temperature without photo- and thermal activation or addition of initiator. The HEMA monomers are first activated during the compression step but their reactivity is hindered by the dense glass-like environment. The rapid polymerization occurs in only the second step upon decompression to the liquid state. The conversion yield was found to exceed 90% in the recovered samples. The gel permeation chromatography evidences the overriding role of HEMA2(**) biradicals in the polymerization mechanism. The HPR process extends the application field of HP-induced polymerization, beyond the family of crystallized monomers considered up today. It is also an appealing alternative to typical photo- or thermal activation, allowing the efficient synthesis of highly pure organic materials. PMID- 26671291 TI - Occurrence of postpericardiotomy syndrome admissions: A population-based registry study. AB - BACKGROUND: Postpericardiotomy syndrome (PPS) is a common complication after cardiac surgery. Previous epidemiological descriptions of the syndrome, however, are scarce. MATERIAL AND METHODS: This retrospective analysis included all patients hospital admission due to PPS in patients aged 20-79 years. Data were collected from the Finnish national registry that included data on all cardiovascular hospital admissions (n = 51 7669) during 9.5 years in 29 Finnish hospitals nationwide. RESULTS: There were 760 hospital admissions due to PPS during the study period. The patients were more likely male than female (67.8% versus 32.2%) with an age-adjusted RR of 2.37 (95% CI 1.85-3.02) for men (p < 0.0001). When evaluating the rate of PPS in relation to cardiac surgeries, female gender was associated with a higher incidence of PPS (RR 1.78; 95% CI 1.45-2.19; p < 0.001). The rate of PPS in relation to the number of cardiac surgery was highest in youngest patients followed by a gradual decrease (RR 0.59; 95% CI 0.55 0.65; p < 0.0001 per 10-year increment in age) with aging. CONCLUSIONS: Hospital admission due to PPS was most common in men in their sixties. When stratified by the total number of performed cardiac operations the incidence of PPS was higher among women and younger patients. PMID- 26671292 TI - Youth blogging and serious illness. AB - In recent years, a growing number of young people who experience illness tend to blog about it. In this paper, we question whether and how illness blogs illustrate the intercommunicative aspect of blogging by bringing forth both the literary concept of the implied reader and the sociological concepts of empowerment and agency in the analysis. We argue that young people blogging about serious illness demonstrate the inherent intercommunicative potential of blogging. We also argue that youth blogging about serious illness may represent a fruitful strategy for ill young people to create meaning, stay front-stage in youth communities and build self-esteem and confidence out of chaos. Furthermore, we argue that these blogs may contribute rather unique experience-based knowledge and reflections about existential issues to other young blog readers, who may otherwise not get access to this aspect of life. Youth blogging about serious illness thereby reflects a patient group so far not very visible and through the genre youth stand out as more competent when it comes to illness and healthcare issues than what is often presumed. PMID- 26671301 TI - The use of positive airway pressure therapy for treatment of resistant hypertension. AB - It is well accepted that obstructive sleep apnea (OSA) is a risk factor for hypertension. In the subgroup of patients with resistant hypertension (rHTN), OSA appears to be particularly rampant; suggesting sleep disordered breathing may contribute to pathological mechanisms that make blood pressure difficult to control. This article explores potential mechanisms by which sleep apnea contributes to rHTN, and examines the impact of treating OSA with positive airway pressure therapy on blood pressure control. In recent years, there has been a surge of interest in randomized controlled trials of positive airway pressure therapy in patients with OSA and rHTN, because patients with rHTN respond poorly to medications. As a result, identifying novel targets for blood pressure control in this high-risk population has become paramount. PMID- 26671302 TI - The determining factor for interstitial oxygen formation in Ruddlesden-Popper type La2NiO4-based oxides. AB - The interstitial oxygen formation mechanism in La2NiO4-based oxides was studied using soft X-ray absorption spectroscopy. When the interstitial oxygen concentration increased, the pre-edge peak of O K-edge spectra increased while Ni L-edge spectra was almost invariant. These spectral changes strongly suggest the significant contribution of ligand oxygen to interstitial oxygen formation by providing/accepting electronic charge carriers. The variation of the integrated peak intensity of the O K-edge strongly suggests that interstitial oxygen formation is determined by the equilibrium unoccupied pDOS of ligand oxygen. From this hypothesis, we propose that modulating the electronic structure is the key to control the capability of interstitial oxygen formation in La2NiO4-based oxides. PMID- 26671300 TI - TP53 Mutational Analysis Enhances the Prognostic Accuracy of IHC4 and PAM50 Assays. AB - IHC4 and PAM50 assays have been shown to provide additional prognostic information for patients with early breast cancer. We evaluated whether incorporating TP53 mutation analysis can further enhance their prognostic accuracy. We examined TP53 mutation and the IHC4 score in tumors of 605 patients diagnosed with stage I-III breast cancer at National Taiwan University Hospital (the NTUH cohort). We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. We found that TP53 mutation was significantly associated with high-risk IHC4 group and with luminal B, HER2-enriched, and basal like subtypes. Despite the strong associations, TP53 mutation independently predicted shorter relapse-free survival (hazard ratio [HR] = 1.63, P = 0.007) in the NTUH cohort and shorter breast cancer-specific survival (HR = 2.35, P = <0.001) in the METABRIC cohort. TP53 mutational analysis added significant prognostic information in addition to the IHC4 score (? LR-chi(2) = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (? LR-chi(2) = 18.9, P = <0.001) in the METABRIC cohort. We conclude that incorporating TP53 mutation analysis can enhance the prognostic accuracy of the IHC4 and PAM50 assays. PMID- 26671303 TI - Comparison of the Effect of Laparoscopic and Abdominal Hysterectomy on Lower Urinary Tract Function, Vaginal Length, and Dyspareunia: A Randomized Clinical Trial. AB - OBJECTIVES: The effect of hysterectomy on vesicourethral and sexual functions remains controversial. The primary objective of this study was to compare the effects of a laparoscopic hysterectomy and a total abdominal hysterectomy on lower urinary tract function. The secondary aims were to compare the two surgeries in terms of postoperative vaginal length and dyspareunia. MATERIALS AND METHODS: This was a prospective randomized clinical study in which 292 women were assigned to either the laparoscopic hysterectomy (n = 146) or total abdominal hysterectomy (n = 146) groups. The vaginal length and urodynamic measurements were taken, and the patients were asked to grade the presence and severity of dyspareunia using a visual analog scale 3 weeks before and 12 weeks after the surgery. The relationship between the postoperative vaginal length and the incidence of dyspareunia was evaluated. The urodynamic procedures used included uroflowmetry and voiding cystometry to record the maximum flow rate (Q-max) and to assess the bladder capacity. RESULTS: The preoperative vaginal length was similar between the groups, whereas the postoperative vaginal length was significantly longer in the laparoscopic hysterectomy group. When the 15 patients who developed postoperative dyspareunia were evaluated, no differences in the postoperative vaginal length were seen, but a significant difference in the change in the length of the vagina was found when compared with the other patients. No significant difference was found with regard to pre- and postoperative Q-max, bladder capacity, and change in bladder capacity between the study groups. CONCLUSIONS: The change in the length of the vagina was much more remarkable after total abdominal hysterectomy, compared with laparoscopic hysterectomy. It seems that the Q-max and the bladder capacity increase after hysterectomies, regardless of the surgical type. Further prospective randomized comparative studies are warranted to ascertain whether laparoscopic hysterectomies cause less damage to the pelvic floor, compared with abdominal hysterectomies. PMID- 26671304 TI - Think Again About Cholesterol Survey. AB - Cardiovascular disease (CVD) is still the main cause of death in Europe. Elevated plasma cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), is the main causative risk factor for CVD, most prominently associated with coronary heart disease. A widespread disinformation about cholesterol and CVD is one factor underlying a poor compliance to lipid-lowering therapy. To investigate how cholesterol, CVD and cholesterol reduction is perceived in the population, a survey was commissioned by the European Atherosclerosis Society (EAS). Nearly half of people above 25 years of age are most worried about cancer (45%), compared to just over one in four who are worried about heart disease (27%). A majority believe being overweight (72%), blood pressure (70%) and smoking (67%) most affect heart health, far more than note cholesterol (59%) and family history (39%). The majority of adults recognize that high LDL (or "bad") cholesterol should be a health priority for everyone, including those younger than 40 and those who are not overweight. However, 1 in 4 (25%) incorrectly believe that it does not need to be a concern until someone shows signs or symptoms. Although 89% of adults surveyed agreed it is important for people to know whether or not they have high LDL-C, an overwhelming 92% did not know their LDL-C levels or had never had their cholesterol levels tested. A high 63% had never heard of familial hypercholesterolemia: France had the lowest level of awareness (41%) to Denmark with a high 80%, and the association of the disease with high levels of LDL-C is quite poor (only 36%), with Sweden only at 22% versus a high in Spain of 54%. A large part of the people participating in the survey were quite uncertain about the modality of transmission for familial hypercholesterolemia in the family. All in all, this survey highlights the need for more information among citizens for the role of cholesterol in determining CVD. PMID- 26671305 TI - Early stage cervical cancer: role of magnetic resonance imaging after conization in determining residual tumor. AB - BACKGROUND: Although magnetic resonance imaging (MRI) is currently indispensable in the management of cervical cancer, its role in determining residual tumor in patients with cervical cancer after conization is not well known. PURPOSE: To evaluate the value of MRI after conization in determining residual tumor in patients with FIGO stage IA-IB1 cervical cancer. MATERIAL AND METHODS: In this retrospective study, 55 patients underwent conization followed by preoperative MRI and definitive surgery. Two radiologists evaluated the presence of residual tumor on MRI. MRI and preoperative clinical variables were compared between patients with and without residual tumor at final pathology using Student's t test or Chi-square test. Association between variables and the presence of residual tumor was assessed using logistic regression analyses and receiver operating characteristic (ROC) curves. RESULTS: Residual tumor at final pathology was found in 30 (54.5%) patients. Patients with residual tumor were older, had greater SCC antigen, and more frequently had positive conization margins and identifiable tumor on MRI (P < 0.008). Multivariate analysis showed that age (P = 0.008; odds ratio [OR] = 1.140), positive conization margin (P = 0.016; OR = 11.919), and identifiable tumor on MRI (P = 0.038; OR = 6.926) were independently predictive of residual tumor. Areas under the curve (AUCs) calculated with age (0.693), SCC antigen (0.755), and identifiable tumor on MRI (0.727) were greater than lymphovascular space invasion (0.517) and histological subtype (0.520, P <= 0.049). Otherwise, there were no significant differences in the AUCs derived from different variables (P = 0.053-0.970). CONCLUSION: Identifiable tumor on MRI after conization in patients with early stage cervical cancer was an independent predictor of residual tumor at final pathology. PMID- 26671306 TI - Partial splenic embolization of patients with hypersplenism by transradial or transfemoral approach: a prospective randomized controlled trial. AB - BACKGROUND: Partial splenic artery embolization (PSE) is an effective treatment modality for patients with hypersplenism. It is less invasive and has a quicker recovery compared with surgical procedures. PSE is usually performed using a femoral artery approach that requires bedrest for a few hours, which is rarely the case for transradial PSE. PURPOSE: To compare the transradial and transfemoral approaches for embolization of spleen in patients with hypersplenism. MATERIAL AND METHODS: In all, 84 patients with hypersplenism who required PSE were recruited. They were randomly divided into two groups on the basis of the procedure followed: the transradial approach (R-PSE, n = 39) or transfemoral approach (F-PSE, n = 45). Technical success, puncture rate, total procedure time, X-ray exposure time, length of stay in hospital (LOS), and complications of the two groups were recorded. RESULTS: The procedure time, X-ray exposure time, and LOS were found to be lower in the R-PSE group than in the F PSE. However, this difference was not statistically significant. CONCLUSION: The transradial artery approach for PSE in patients with hypersplenism is feasible with no major complications as compared to the femoral approach. PMID- 26671308 TI - When Layered Nickel-Cobalt Silicate Hydroxide Nanosheets Meet Carbon Nanotubes: A Synergetic Coaxial Nanocable Structure for Enhanced Electrocatalytic Water Oxidation. AB - Developing robust earth-abundant electrocatalysts for oxygen evolution reaction (OER) is an ongoing scientific challenge, which is coupled with a number of important electrochemical processes and many key renewable energy systems, such as water splitting, rechargeable metal-air batteries, and regenerative fuel cells. Here, we proposed a rational design and fabrication of the synergetic coaxial nanocable structures by intimate growth of the layered nickel-cobalt silicate hydroxide nanosheets on the outer surfaces of multiwalled carbon nanotubes (MWCNTs@NCS) and demonstrated their high efficiency in electrocatalytic OER from water splitting. The electrocatalytic activities of the MWCNTs@NCS were found to be significantly higher than that of bare NCS and pristine MWCNTs, synergetically determining by such the constituted individual components. Among them, the MWCNTs@NCS-2 exhibited best electrocatalytic OER performance, showing a small OER onset potential, large anodic current and long-term durability, which was favorably comparable to the previously reported NiCo-based OER electrocatalysts in alkaline electrolytes. To the best of our knowledge, this was a first example on the earth-abundant metal silicate hydroxides utilized in electrochemical water splitting. PMID- 26671307 TI - Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea. AB - BACKGROUND: Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient's phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS). METHODS: Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern. RESULTS: 30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p<0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%. CONCLUSION: Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individual's metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible. TRIAL REGISTRATION NUMBER: NCT02050425 (registered at ClinicalTrials.gov). PMID- 26671309 TI - A novel and easy FxCycleTM violet based flow cytometric method for simultaneous assessment of DNA ploidy and six-color immunophenotyping. AB - Abnormal DNA ploidy is a valuable prognostic factor in many neoplasms, especially in hematological neoplasms like B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM). Current methods of flow-cytometric (FC) DNA-ploidy evaluation are either technically difficult or limited to three- to four-color immunophenotyping and hence, challenging to evaluate DNA-ploidy in minute tumor population with background rich of its normal counterpart cells and other hematopoietic cells. We standardized a novel sensitive and easy method of simultaneous evaluation of six- to seven-color immunophenotyping and DNA-ploidy using a dye-FxCycle Violet (FCV). Linearity, resolution, and coefficient of variation (CV) for FCV were studied using chicken erythrocyte nuclei. Ploidy results of FCV were compared with Propidium iodide (PI) in 20 samples and intra assay variation for FCV was studied. Using this six-color immunophenotyping & FCV protocol DNA-ploidy was determined in bone-marrow samples from 124 B-ALL & 50 MM patients. Dilution experiment was also conducted to determine the sensitivity in detection of aneuploidy in minute tumor population. FCV revealed high linearity and resolution in 450/50 channel. On comparison with PI, CV of Go/G1-peak with FCV (mean-CV 4.1%) was slightly higher than PI (mean-CV 2.9%) but had complete agreement in ploidy results. Dilution experiment showed that aneuploidy could be accurately detected up to the limit of 0.01% tumor cells. Intra-assay variation was very low with CV of 0.005%. In B-ALL, hypodiploidy was noted in 4%, hyperdiploidy in 24%, near-hyperdiploidy in 13% and remaining 59% were diploid. In MM, hypodiploidy was in 2%, hyperdiploidy in 58%, near-hyperdiploidy in 8% and remaining 30% were diploid. FCV-based DNA-ploidy method is a sensitive and easy method for simultaneous evaluation of six-color immunophenotyping and DNA analysis. It is useful in DNA-ploidy evaluation of minute tumor population in cases like minimal residual disease and MM precursor conditions. PMID- 26671310 TI - Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma. AB - Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure. PMID- 26671311 TI - Selected Issues in Injury and Illness Prevention and the Team Physician: A Consensus Statement. PMID- 26671312 TI - A simple estimation of ideal profile of essential amino acids and metabolizable energy for growing Japanese quail. AB - An experiment was conducted to determine apparent metabolizable energy (AME) and amino acid requirements of growing Japanese quail based on ideal protein concept using artificial neural network and desirability function (D-ANN). Seven-day-old quail chicks were assigned to nine experimental diets based on central composite design (CCD) containing five levels of AME (2809-3091 kcal/kg) and CP (19-24.8% of diet). The ratio of lysine (Lys) to CP was set at 0.053 among all treatments, and remaining essential amino acids (EAA) were adjusted to Lys. The experimental data of CCD were fitted to D-ANN model to compute the optimal values for independent variables. The optimal values of inputs including AME, CP, digestible Lys (dLys), methionine (dMet), total sulphur amino acids (dTSAA), threonine (dThr), tryptophan (dTrp), isoleucine (dIle), valine (dVal) and arginine (dArg) for maximizing gain and minimizing feed conversion ratio were estimated at 2865 kcal/kg, 25, 1.32, 0.55, 0.88, 0.84, 0.20, 0.75, 1.04 and 1.45% of diet, respectively, with D (desirability function) = 0.94. The corresponding optimal amounts of amino acids based on total amino acids were 1.42, 0.59, 0.95, 0.90, 0.22, 0.81, 1.12 and 1.56% of diet respectively. The ideal pattern of essential amino acids to Lys was as follows: dMet: dLys = 0.42, dTSAA: dLys = 0.67, dThr: dLys = 0.64, dTrp: dLys = 0.15, dIle: dLys = 0.57, dVal: dLys = 0.79 and dArg: dLys = 1.09. The results of this study showed that amino acid requirements of modern quails might be higher than those reported by NRC. PMID- 26671313 TI - A multileveled approach in psoriasis assessment and follow-up: A proposal for a tailored guide for the dermatological practice. AB - BACKGROUND: Psoriasis is a complex and heterogeneous disease resulting from interactions between genetic, immunological, and environmental factors. To make the most optimal treatment decision, the dermatologist must therefore have a detailed overview of the patient's history and lifestyle. OBJECTIVES: We sought to offer an overview of the various relevant aspects in clinical dermatological assessment of psoriasis patients, emphasizing the importance of a multidisciplinary and integrated clinical approach. METHODS: We gathered information on psoriasis management and developed a tailored checklist covering all health-related aspects associated with psoriasis. RESULTS: Demographics, personal and family history were elaborately described as well as drug history to discuss how they affect psoriasis management. Relevant patient information such as the vaccination status or cardiovascular profile were included in the checklist as well and treatment recommendations were adapted and updated in accordance with evidence-based literature. This checklist also emphasizes the importance of drug surveillance, proper follow-up and specialist referral, and why the dermatologist needs to address these health-related aspects when assessing psoriasis patients, going beyond optimal skin care. CONCLUSIONS: Our comprehensive overview can be used as a consultation checklist for good clinical practice in psoriasis patient management and aid in treatment decision. PMID- 26671314 TI - Multiple resections and survival of recurrent glioblastoma patients in the temozolomide era. AB - Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor in adults for which recurrence is inevitable and surgical resection is often recommended. We investigated the relationship between multiple tumor resections and overall survival (OS) in adult glioblastoma patients who received adjuvant radiotherapy and temozolomide following initial surgery. We retrospectively reviewed the records of all newly diagnosed adult GBM patients with tumor recurrence at our institution from March 2003 to October 2012. Kaplan-Meier survival estimates and multivariate analysis using Cox's proportional hazards model were utilized to evaluate the impact of multiple resections on OS. A total of 202 GBM patients were analyzed; 83 (41.1%), 94 (46.5%), and 25 (12.4%) patients underwent one, two, and three or more total resections, respectively. Patients who underwent multiple resections were significantly younger (p<0.0001) and had higher perioperative Karnofsky Performance Status scores (p<0.0001) than single resection patients. The median OS in months was 21.1, 25.5, and 29.0 for patients who had one, two, and three or more resections, respectively (Wilcoxon p=0.03). In a confounder-adjusted multivariate model, patients with multiple resections did not have significantly improved survival (p=0.55). Older age was strongly associated with poorer OS (hazard ratio 1.34, p<0.0001). Age at diagnosis was the only predictor of survival for recurrent GBM patients. After adjusting for age at diagnosis, multiple resections were not an independent predictor of OS in our glioblastoma cohort treated in the temozolomide era. PMID- 26671316 TI - Effects of Threshold Adjustment on Speech Perception in Nucleus Cochlear Implant Recipients. AB - OBJECTIVE: The objective of this study was to investigate the impact of using smaller and larger electric dynamic ranges on speech perception, aided thresholds, and subjective preference in cochlear implant (CI) subjects with the Nucleus device. DESIGN: Data were collected from 19 adults using the Nucleus CI system. Current levels (CLs) used to set threshold stimulation levels (T-levels) were set above or below the measured hearing thresholds to create smaller or larger electric output dynamic ranges, respectively, whereas the upper stimulation level (C-level) was fixed. The base (unadjusted) condition was compared against two conditions with higher T-levels (compression), by 30% and 60% of the measured hearing dynamic range, and three conditions with lower T levels (expansion), by 30%, 60%, and 90% of the measured hearing dynamic range. For each subject, the clinical CL units were adjusted on each electrode to achieve these conditions. The slow-acting dynamic acoustic gains of ADRO and AutosensitivityTM were enabled. Consonant-nucleus-consonant (CNC) word scores were measured in quiet at 50 dB and 60 dB SPL presentation levels. The signal-to noise ratios (SNRs) for 50% understanding of sentences in noise were measured for sentences presented at 55 dB and 65 dB SPL in 4-talker babble noise. Free-field aided thresholds were measured at octave frequencies using frequency-modulated (warble) tones. Thirteen of the 19 subjects had take-home experience with the base and experimental conditions and provided subjective feedback via a questionnaire. RESULTS: There were no significant effects of 30% expansion and 30% compression of the electric dynamic range on scores for words in quiet and SNRs for sentences in noise, at the two presentation levels. There was a significant decrement in scores for words in quiet for 60% and 90% expansion compared with the base condition at the 50 dB and 60 dB SPL presentation levels. The score decrement was much less at 60 dB SPL. For the 50 dB SPL presentation level, the decrements in word scores at 60% and 90% expansion were linearly related to the reduction in CL units required to achieve these experimental conditions, with a greater decrement in scores for a larger CL change. There was a significant increase in SNR for sentences in noise for 60% compression compared with the base condition at the 55 dB and 65 dB SPL presentation levels. There was also a significant increase in SNR for sentences at the 55 dB SPL presentation level for 90% expansion. Aided thresholds were significantly elevated for the three expansion conditions compared with the base condition, although the mean elevation at 30% expansion was only 4 dB. The questionnaire results showed no clear preference for any condition; however, subjects reported a reduced preference for the extreme compression (60%) and expansion (90%) conditions. CONCLUSIONS: The results showed that CI subjects using the Nucleus sound processor had no significant change in performance or preference for adjustments in T-levels by +/-30% of the hearing dynamic range. In quiet, speech perception scores were reduced for the more marked expansion (60% and 90%) conditions, whereas in noise, performance was poorer for the highest compression (60%) condition. Across subjects, the decrement in scores for words at 50 dB SPL for the 60% and 90% expansion conditions was related to the changes in CL units required for these conditions, with greater decrements for larger changes in levels. PMID- 26671315 TI - Off to the Right Start: Well-Child Visit Attendance Among Health Center Users. AB - INTRODUCTION: This study examines correlates of past-year well-child visit attendance, reasons for choosing to receive care at a health center, and patient experience among pediatric federally qualified health center users. METHOD: This observational study used cross-sectional 2009 Health Center Patient Survey data. Descriptive statistics, bivariate analysis, and multivariable models were utilized. RESULTS: This study found that 83.0% of children who visited a health center in the past year had a well-child visit in the past year and 88.5% had a usual source of care, with no disparities based on race/ethnicity or insurance status. A usual source of care, especially a health center, enhanced well-child visit attendance. The top reasons for seeking care at a health center include convenience (31.6%), quality (24.5%), accessibility (17.7%), and co-located nonmedical services (11.5%). DISCUSSION: Well-child visit attendance is high but there is room for improvement, particularly among patients who lack a usual source of care. PMID- 26671317 TI - The Use of the Kurtosis-Adjusted Cumulative Noise Exposure Metric in Evaluating the Hearing Loss Risk for Complex Noise. AB - OBJECTIVE: To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically, to evaluate whether the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss, and (2) provides a single metric applicable to both complex (non-Gaussian [non-G]) and continuous or steady state (Gaussian [G]) noise exposures for predicting noise induced hearing loss (dose-response curves). DESIGN: Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N = 178) were exposed to complex noise, whereas the subjects from textile manufacturing plant (N = 163) were exposed to a G continuous noise. Each subject was given an otologic examination to determine their pure-tone HTL and had their personal 8-hr equivalent A-weighted noise exposure (LAeq) and full-shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject, an unadjusted and kurtosis-adjusted CNE index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis adjusted) and the mean HTL at 3, 4, and 6 kHz (HTL346) among the complex noise-exposed group. In addition, each subject's HTLs from 0.5 to 8.0 kHz were age and sex adjusted using Annex A (ISO-1999) to determine whether they had adjusted high-frequency noise induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0, or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric. RESULTS: Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared with the unadjusted CNE (R = 0.386 versus 0.350) and that noise accounted for a greater proportion of hearing loss. In addition, although dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE. CONCLUSIONS: For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than in workers exposed to a continuous noise. Kurtosis adjustment of CNE improved the correlation with NIHL and provided a single metric for dose-response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments. PMID- 26671318 TI - Accuracy of the Broselow Tape in South Sudan, "The Hungriest Place on Earth". AB - OBJECTIVES: The Broselow tape is a length-based tool used for the rapid estimation of pediatric weight and was developed to reduce dosage-related errors during emergencies. This study seeks to assess the accuracy of the Broselow tape and age-based formulas in predicting weights of South Sudanese children of varying nutritional status. METHODS: This was a retrospective, cross-sectional study using data from existing acute malnutrition screening programs for children less than 5 years of age in South Sudan. Using anthropometric measurements, actual weights were compared with estimated weights from the Broselow tape and three age-based formulas. Mid-upper arm circumference was used to determine if each child was malnourished. Broselow accuracy was assessed by the percentage of measured weights falling into the same color zone as the predicted weight. For each method, accuracy was assessed by mean percentage error and percentage of predicted weights falling within 10% of actual weight. All data were analyzed by nutritional status subgroup. RESULTS: Only 10.7% of malnourished and 26.6% of nonmalnourished children had their actual weight fall within the Broselow color zone corresponding to their length. The Broselow method overestimated weight by a mean of 26.6% in malnourished children and 16.6% in nonmalnourished children (p < 0.001). Age-based formulas also overestimated weight, with mean errors ranging from 16.2% over actual weight (Advanced Pediatric Life Support in nonmalnourished children) to 70.9% over actual (Best Guess in severely malnourished children). CONCLUSIONS: The Broselow tape and age-based formulas selected for comparison were all markedly inaccurate in both the nonmalnourished and the malnourished populations studied, worsening with increasing malnourishment. Additional studies should explore appropriate methods of weight and dosage estimation for populations of low- and low-to-middle-income countries and regions with a high prevalence of malnutrition. PMID- 26671319 TI - RpoS differentially affects the general stress response and biofilm formation in the endophytic Serratia plymuthica G3. AB - The sigma(S) subunit RpoS of RNA polymerase functions as a master regulator of the general stress response in Escherichia coli and related bacteria. RpoS has been reported to modulate biocontrol properties in the rhizobacterium Serratia plymuthica IC1270. However, the role of RpoS in the stress response and biofilm formation in S. plymuthica remains largely unknown. Here we studied the role of RpoS from an endophytic S. plymuthica G3 in regulating these phenotypes. Mutational analysis demonstrated that RpoS positively regulates the global stress response to acid or alkaline stresses, oxidative stress, hyperosmolarity, heat shock and carbon starvation, in addition to proteolytic and chitinolytic activities. Interestingly, rpoS mutations resulted in significantly enhanced swimming motility, biofilm formation and production of the plant auxin indole-3 acetic acid (IAA), which may contribute to competitive colonization and environmental fitness for survival. These findings provide further insight into the strain-specific role of RpoS in the endophytic strain G3 of S. plymuthica, where it confers resistance to general stresses encountered within the plant environment. The heterogeneous functionality of RpoS in rhizosphere and endophytic S. plymuthica populations may provide a selective advantage for better adaptation to various physiological and environmental stresses. PMID- 26671320 TI - Incidence and risk factors associated with iron deficiency anaemia among hospitalised Lebanese infants. AB - OBJECTIVES: The primary objective of this study was to determine the prevalence of iron deficiency anaemia (IDA) in hospitalised 6- to 24-month-old infants in rural versus urban settings. The secondary objective was to determine associated risk factors in rural versus urban settings. METHODS: A 6-month prospective multicentre cross-sectional study was conducted in paediatrics departments of three Lebanese hospitals. Preterm to term infants aged 6-24 months were included. Infants with blood disorders, chronic infections, congenital immunodeficiency and mental or congenital growth retardation were excluded. Incidence of IDA was assessed using haematologic laboratory values, while risk factors were assessed using questionnaires addressed to infants' caregivers. For data analysis, P values, chi-squared and logistic regression were used. KEY FINDINGS: Among 520 screened infants, a total of 100 patients were selected. Thirty-seven per cent of patients were anaemic with haemoglobin levels <11 g/dl. Significant risk factors included: exclusive breastfeeding for more than 6 months (95% CI, 1.03 to 8.9; P = 0.043), low family income (95% CI, 0.19 to 0.98; P = 0.045), residing in rural areas (95% CI, 0.064 to 0.0509; P < 0.001), inadequate maternal iron supply (95% CI, 1.01 to 8.26; P = 0.05), low maternal education level (95% CI, 0.07 to 0.88; P = 0.03) and lack of infant iron supply (95% CI, 1.39 to 8.41; P = 0.007). CONCLUSION: Incidence of IDA among Lebanese infants is moderate and multifactorial. High maternal education level, urban residence, giving iron supplements to exclusively breastfed infants starting from 6 months of age, adequate family income and iron supplementation in both mother and infant are significant protective factors against anaemia in this population. PMID- 26671321 TI - Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis. AB - The ceramide phosphoinositol glycan core (CPI-GC) of the lipophosphoglycan of Trichomonas vaginalis is a major virulent factor of this common genitourinary parasite. While its carbohydrate composition has been reported before, its structure has remained largely unknown. We isolated the glycan portions of CPI-GC by nitrous acid deamination and hydrofluoric acid treatment and investigated their structures by methylation analysis and 1- and 2-D NMR. We found that the alpha-anomer of galactose is a major constituent of CPI-GC. The beta-anomer was found exclusively at the non-reducing end of CPI-GC side chains. Furthermore the data showed that the rhamnan backbone is more complex than previously thought and that the inositol residue at the reducing end is linked to a 4-linked alpha glucuronic acid (GlcA) residue. This appears to be the most striking and novel feature of this GPI-anchor type molecule. PMID- 26671322 TI - [Majocchi granuloma. Presentation of a case in Primary Care]. PMID- 26671323 TI - [Atypical constitutional syndrome]. PMID- 26671324 TI - [Non-steroidal anti-inflammatory drugs and antidepressants, a dangerous combination]. PMID- 26671325 TI - [Treating pain with non-prescription pain relievers: Aspirin, paracetamol and ibuprofen]. PMID- 26671326 TI - [Presentation of a case: Foreign body in colon in a regional hospital emergency department]. PMID- 26671327 TI - [Empagliflozin reduces cardiovascular mortality in diabetic patients with previous cardiovascular events]. PMID- 26671328 TI - [Presentation of a case of Wallenberg syndrome]. PMID- 26671329 TI - [Developments in the medical treatment of overactive bladder]. AB - Overactive Bladder (OAB) is a common problem among men and women. Antimuscarinic drugs are a reference treatment for OAB and act by blocking the muscarinic receptors (M2 and M3 subtypes) in the bladder. Adherence to antimuscarinic treatment is usually low, due to the perceived lack of efficacy and adverse effects. Therefore, new treatments with different mechanisms of action and a more acceptable tolerability profile are needed, and that improve the symptoms of OAB. Mirabegron is a new treatment option for all patients with OAB and could solve an unmet need in patients still not satisfied, or where the antimuscarinic therapy is not indicated, is an alternative option for patients with OAB. PMID- 26671330 TI - Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK-6577 in baboons. AB - Glycine transporter type-1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [(11) C]GSK931145, and [(18) F]MK-6577, in baboons. Two baboons were imaged with [(11) C]GSK931145 and [(18) F]MK-6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [(11) C]GSK931145 and [(18) F]MK 6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ~ 30% of parent at 30 min post injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [(18) F]MK-6577 displayed higher uptake and faster kinetics than [(11) C]GSK931145. Time activity curves were well described by the two-tissue compartment model. Regional volume of distribution (VT ) values were higher for [(18) F]MK-6577 than [(11) C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of VT estimates between tracers indicated higher specific binding for [(18) F]MK-6577 than [(11) C]GSK931145, consistent with higher regional binding potential (BPND ) values of [(18) F]MK-6577 calculated using VT from the baseline scans and non displaceable distribution volume (VND ) derived from blocking studies. [(18) F]MK 6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [(11) C]GSK931145. PMID- 26671331 TI - A Comprehensive Study of Extramural Venous Invasion in Colorectal Cancer. AB - Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI). It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928) that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (chi2 = 12.03, p<0.005), tumour stage (chi2 = 268.188, p<0.001), lymph node stage (chi2 = 294.368, p<0.001) and Dukes' stage (chi2 = 253.753, p<0.001). Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001). In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors. PMID- 26671332 TI - Quantitative developmental transcriptomes of the Mediterranean sea urchin Paracentrotus lividus. AB - Embryonic development progresses through the timely activation of thousands of differentially activated genes. Quantitative developmental transcriptomes provide the means to relate global patterns of differentially expressed genes to the emerging body plans they generate. The sea urchin is one of the classic model systems for embryogenesis and the models of its developmental gene regulatory networks are of the most comprehensive of their kind. Thus, the sea urchin embryo is an excellent system for studies of its global developmental transcriptional profiles. Here we produced quantitative developmental transcriptomes of the sea urchin Paracentrotus lividus (P. lividus) at seven developmental stages from the fertilized egg to prism stage. We generated de-novo reference transcriptome and identified 29,817 genes that are expressed at this time period. We annotated and quantified gene expression at the different developmental stages and confirmed the reliability of the expression profiles by QPCR measurement of a subset of genes. The progression of embryo development is reflected in the observed global expression patterns and in our principle component analysis. Our study illuminates the rich patterns of gene expression that participate in sea urchin embryogenesis and provide an essential resource for further studies of the dynamic expression of P. lividus genes. PMID- 26671333 TI - A tale of two epidemics: gender differences in socio-demographic characteristics and sexual behaviors among HIV positive individuals in Mexico City. AB - BACKGROUND: To date, the HIV epidemic in Mexico has been concentrated mainly among men who have sex with men, butheterosexual transmission, particularly to women, is increasingly important. This study examine gender differences in socio demographic characteristics and risk behaviors of HIV positive individuals in Mexico City. METHODS: We analyzed data from a cross-sectional survey of 1,490 clinic patients (male:female ratio 8:1) with HIV inMexico City in 2010. We examined socio-demographic characteristics, risk behavior, and history of HIV infection.From multivariate non-linear probability (probit) models we calculated predicted probabilities by sex of several outcomes: marginalization, demographic and sexual risk behaviors. RESULTS: Significant differences were found between men and women. Multivariate models suggest that women had lower schooling levels; were less likely to have been employed in the past month and earn more than the minimal wage; more likely to have children, to have been sexually abused, to never have used condoms and to report having been infected by a stable partner. Additionally, women were less likely to report having a partner with a history of migration to the USA and to have engaged in transactional sex. CONCLUSION: Significant differences exist between men and women with HIV in Mexico City in terms of their socioeconomicand behavioral profiles, which translate into differences in terms of exposure to HIV infection. Women face social and economic vulnerability while men tend to have riskier sexual behavior. Gender issues must be approached in prevention and treatment efforts, using diverse methods to target those most vulnerable and at risk. PMID- 26671334 TI - Mycobacterium bovis hip bursitis in a lung transplant recipient. AB - We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico-US border, clinical characteristics, resistance profile, and treatment. PMID- 26671338 TI - Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States. AB - BACKGROUND: Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. METHODS AND FINDINGS: The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged >= 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. CONCLUSIONS: Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events. PMID- 26671341 TI - Distribution of Mycobacterium avium subsp. paratuberculosis in a Subclinical Naturally Infected German Fleckvieh Bull. AB - Although it has been known for years that Mycobacterium avium subsp. paratuberculosis (MAP) is detectable in the reproductive organs and semen of infected bulls, only few studies have been conducted on this topic worldwide. This study surveyed the MAP status of a bull, naturally infected due to close contact with its subclinically infected parents over a period of 4 years. From the age of 7 weeks to necropsy, faecal, blood and, after sexual maturity, semen samples were drawn repeatedly. Already at the first sampling day, MAP-DNA was detected in faeces by semi-nested PCR. True infection was confirmed by the detection of MAP-DNA in blood at the age of 40 weeks. In total, MAP-DNA was present in 25% faecal (34/139), 16% blood (23/140) and 5% semen (4/89) samples, including MAP-free intervals of up to 9 weeks. MAP genome equivalents (MAP-GE) of up to 6.3 * 106 /g faeces and 1.8 * 105 /ml blood were determined. Cultivation of MAP occurred only in three of 137 faecal and two of 109 blood, but never in semen samples. Over the whole period, the bull was a serological negative MAP shedder. During necropsy, 42 tissue samples were collected. Neither macroscopic nor histological lesions characteristic of a MAP infection were observed. Cultivation of MAP in tissue sections failed. However, MAP-DNA was spread widely in the host, including in tissues of the lymphatic system (7/15), digestive tract (5/14) and the urogenital tract (5/9) with concentrations of up to 3.9 * 106 MAP-GE/g tissue. The study highlighted the detection of MAP in male reproductive organs and semen. It supports the hypothesis that bulls may probably transmit MAP, at least under natural mating conditions. In artificial insemination, this might not be relevant, due to antibiotics included currently in semen extenders. However, the survivability of MAP in this microenvironment should be investigated in detail. PMID- 26671342 TI - Retinoic Acid Signaling Is Essential for Valvulogenesis by Affecting Endocardial Cushions Formation in Zebrafish Embryos. AB - Retinoic acid (RA) plays important roles in many stages of heart morphogenesis. Zebrafish embryos treated with exogenous RA display defective atrio-ventricular canal (AVC) specification. However, whether endogenous RA signaling takes part in cardiac valve formation remains unknown. Herein, we investigated the role of RA signaling in cardiac valve development by knocking down aldh1a2, the gene encoding an enzyme that is mainly responsible for RA synthesis during early development, in zebrafish embryos. The results showed that partially knocking down aldh1a2 caused defective formation of primitive cardiac valve leaflets at 108 hpf (hour post-fertilization). Inhibiting endogenous RA signaling by 4 diethylaminobenzal-dehyde revealed that 16-26 hpf was a key time window when RA signaling affects the valvulogenesis. The aldh1a2 morphants had defective formation of endocardial cushion (EC) at 76 hpf though they had almost normal hemodynamics and cardiac chamber specification at early development. Examining the expression patterns of AVC marker genes including bmp4, bmp2b, nppa, notch1b, and has2, we found the morphants displayed abnormal development of endocardial AVC but almost normal development of myocardial AVC at 50 hpf. Being consistent with the reduced expression of notch1b in endocardial AVC, the VE-cadherin gene cdh5, the downstream gene of Notch signaling, was ectopically expressed in AVC of aldh1a2 morphants at 50 hpf, and overexpression of cdh5 greatly affected the formation of EC in the embryos at 76 hpf. Taken together, our results suggest that RA signaling plays essential roles in zebrafish cardiac valvulogenesis. PMID- 26671343 TI - Five London areas to get devolved power over health. PMID- 26671340 TI - Evaluation of the Family Integrated Care model of neonatal intensive care: a cluster randomized controlled trial in Canada and Australia. AB - BACKGROUND: Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant's care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care. METHODS/DESIGN: FICare is being evaluated in a cluster randomized controlled trial among infants born at <= 33 weeks' gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant's care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants' weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student's t-test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials. DISCUSSION: By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care. TRIAL REGISTRATION: NCT01852695 , registered December 19, 2012. PMID- 26671344 TI - A timesaving, low-cost, high-yield method for the synthesis of ultrasmall uniform graphene oxide nanosheets and their application in surfactants. AB - Graphene oxide nanosheets (GONSs) with a lateral size less than 100 nm have attracted more and more attention for their wide range of potential applications, from bionanotechnology and nanobiomedicine to surfactants. However, at present GONSs are commonly prepared from graphite nanofibers or graphite nanopowders which are both expensive. Here, a timesaving, low-cost, high-yield method is proposed for preparing ultrasmall uniform GONSs with an average lateral size of ~30 nm, utilizing common graphite powder as the raw material in the absence of a strong acid. The obtained GONSs are able to disperse single-walled carbon nanotubes (SWCNTs) effectively, and the dispersion could withstand high-speed centrifugation. Consequently, GONSs could indeed serve as a superior surfactant for the dispersion of SWCNTs, and the dispersion could be further applied in electronics, as the GONSs may be further reduced to reduced GONSs or graphene nanosheets. PMID- 26671345 TI - Remedial after-school support classes offered in rural Gambia (The SCORE trial): study protocol for a cluster randomized controlled trial. AB - BACKGROUND: Low education levels are endemic in much of the developing world, particularly in rural areas where traditional government-provided public services often have difficulty reaching beneficiaries. Providing trained para-teachers to teach regular after-school remedial education classes has been shown to improve literacy and numeracy in children of primary school age residing in such areas in India. This trial investigates whether such an intervention can also be effective in a West African setting with similarly low learning levels and difficult geographic access. METHODS/DESIGN: DESIGN: cluster-randomized controlled trial. Clusters: villages or groups of villages with 15-300 households and at least 15 eligible children in the Lower River and North Bank Regions of The Gambia. PARTICIPANTS: children born between 1 September 2007 and 31 August 2009 planning to enter the first grade, for the first time, in the 2015-2016 school year in eligible villages. We anticipate enrolling approximately 150 clusters of villages with approximately 6000 children as participants. INTERVENTION: a program providing remedial after-school lessons, focusing on literacy and numeracy, 5 to 6 days a week for 3 years to eligible children, based on the intervention evaluated in the Support To Rural India's Public Education System (STRIPES) trial (PLoS ONE 8(7):e65775). CONTROL: both the intervention and control groups will receive small bundles of useful materials during annual data collection as recompense for their time. If the education intervention is shown to be cost effective at raising learning levels, it is expected that the control group villages will receive the intervention for several years after the trial results are available. OUTCOMES: the primary outcome of the trial is a composite mathematics and language test score. Secondary outcomes include school attendance, enrollment, performance on nationally administered exams, parents' spending on education, spillover learning to siblings and family members, and school-related time use of parents and children. Subgroup analyses of the primary outcome will also be carried out based on ethnic group, gender, distance from the main highway, parents' education level, and school type. The trial will run by independent research and implementation teams and supervised by a Trial Steering Committee. DISCUSSION: Along with the overall impact of the intervention, we will conduct a cost-effectiveness analysis. There are no major ethical issues for this study. TRIAL REGISTRATION: Current controlled trials ISRCTN12500245 . 1 May 2015. PMID- 26671346 TI - Safety and efficacy of minimally invasive percutaneous nephrolithotomy in the treatment of patients with medullary sponge kidney. AB - The purpose of this study was to review the safety and efficacy of the minimally invasive percutaneous nephrolithotomy in the treatment of medullary sponge kidney patients with complex renal calculi. Sixteen medullary sponge kidney patients with complex renal calculi underwent minimally invasive percutaneous nephrolithotomy procedures in our center were entered into this retrospective study. The data analyzed included patients' demographics, stone burden, operative time, operative blood loss, length of hospital stay, complications according to the modified Clavien system, and stone-free rate. All the patients in this study had complex renal stones that included 14 multiple stones and 3 partial staghorn calculi. The mean stone surface area was 779.5 +/- 421.1 mm(2). Preoperative urinary tract infection was noted in 5 (31.2 %) patients. Minimally invasive percutaneous nephrolithotomy was successfully completed in 15 renal units in 14 patients. Two patients failed the procedure. The mean operative time was 87.3 +/- 32.3 min. Mean hemoglobin drop was 25.3 +/- 16.5 g/L. An initial stone-free rate of 60 % was achieved after the procedure, and the final stone-free rate was 86.6 % after auxiliary second look and/or shock-wave lithotripsy. Clavien grade I and II complications occurred in 3 (21.4 %) patients including the one (7.1 %) patient who required transfusion. All the complications were managed conservatively. No major complications occurred. This retrospective analysis confirmed that minimally invasive percutaneous nephrolithotomy was a safe alternative treatment for the medullary sponge kidney patients with complex renal calculi. This procedure provided an acceptable stone-free rate and low incidence of high-grade complications. Stone-free rate further could be further improved with auxiliary procedures. PMID- 26671347 TI - Muscle damage and repeated bout effect induced by enhanced eccentric squats. AB - BACKGROUND: Muscle damage and repeated bout effect have been studied after pure eccentric-only exercise. The aim of this study was to evaluate muscle damage and repeated bout effect induced by enhanced eccentric squat exercise using flywheel device. METHODS: Thirteen healthy males volunteered for this study. Creatine kinase blood activity (CK), quadriceps isometric peak torque and muscle soreness were used as markers of muscle damage. The dependent parameters were measured at baseline, immediately after and each day up to 96 hours after the exercise session. The intervention consisted of 100 repetitions of enhanced eccentric squat exercise using flywheel device. The same protocol was repeated after 4 weeks. RESULTS: After the first bout, CK and muscle soreness were significantly greater (P<0.05) than baseline respectively up to 72 and 96 hours. Isometric peak torque was significantly lower (P<0.05) up to 72 hours. After the second bout, CK showed no significant increase (P>0.05), while isometric peak torque and muscle soreness returned to values similar to baseline after respectively 48 and 72 hours. All muscle damage markers were significantly lower after second compared to first bout. CONCLUSIONS: The enhanced eccentric exercise induced symptoms of muscle damage up to 96 hours. However, it provided muscle protection after the second bout, performed four weeks later. Although it was not eccentric-only exercise, the enhancement of eccentric phase provided muscle protection. PMID- 26671348 TI - Enhancing the carbon capture capacities of a rigid ultra-microporous MOF through gate-opening at low CO2 pressures assisted by swiveling oxalate pillars. AB - Porosity enhancement assisted by an unusual gate opening has been realized in an exceptionally rigid ultra-microporous framework. The gate-opening has been attributed to the presence of symmetrically positioned Zn-O bonds of the Zn oxalate units that facilitate subtle swiveling motion resulting in a drastic improvement (42%) in the CO2 capacity without compromising the CO2/N2 selectivity. PMID- 26671349 TI - Communication: High pressure specific heat spectroscopy reveals simple relaxation behavior of glass forming molecular liquid. AB - The frequency dependent specific heat has been measured under pressure for the molecular glass forming liquid 5-polyphenyl-4-ether in the viscous regime close to the glass transition. The temperature and pressure dependences of the characteristic time scale associated with the specific heat is compared to the equivalent time scale from dielectric spectroscopy performed under identical conditions. It is shown that the ratio between the two time scales is independent of both temperature and pressure. This observation is non-trivial and demonstrates the existence of specially simple molecular liquids in which different physical relaxation processes are both as function of temperature and pressure/density governed by the same underlying "inner clock." Furthermore, the results are discussed in terms of the recent conjecture that van der Waals liquids, like the measured liquid, comply to the isomorph theory. PMID- 26671350 TI - Communication: Vibrationally resolved photoelectron spectroscopy of the tetracyanoquinodimethane (TCNQ) anion and accurate determination of the electron affinity of TCNQ. AB - Tetracyanoquinodimethane (TCNQ) is widely used as an electron acceptor to form highly conducting organic charge-transfer solids. Surprisingly, the electron affinity (EA) of TCNQ is not well known and has never been directly measured. Here, we report vibrationally resolved photoelectron spectroscopy (PES) of the TCNQ(-) anion produced using electrospray and cooled in a cryogenic ion trap. Photoelectron spectrum taken at 354.7 nm represents the detachment transition from the ground state of TCNQ(-) to that of neutral TCNQ with a short vibrational progression. The EA of TCNQ is measured accurately to be 3.383 +/- 0.001 eV (27,289 +/- 8 cm(-1)), compared to the 2.8 +/- 0.1 eV value known in the literature and measured previously using collisional ionization technique. In addition, six vibrational peaks are observed in the photoelectron spectrum, yielding vibrational frequencies for three totally symmetric modes of TCNQ. Two photon PES via a bound electronic excited state of TCNQ(-) at 3.100 eV yields a broad low kinetic energy peak due to fast internal conversion to vibrationally excited levels of the anion ground electronic state. The high EA measured for TCNQ underlies its ability as a good electron acceptor. PMID- 26671351 TI - Communication: An accurate full 15 dimensional permutationally invariant potential energy surface for the OH + CH4 -> H2O + CH3 reaction. AB - A globally accurate full-dimensional potential energy surface (PES) for the OH + CH4 -> H2O + CH3 reaction is developed using the permutation invariant polynomial neural network approach based on ~135,000 points at the level of correlated coupled cluster singles, doubles, and perturbative triples level with the augmented correlation consistent polarized valence triple-zeta basis set. The total root mean square fitting error is only 3.9 meV or 0.09 kcal/mol. This PES is shown to reproduce energies, geometries, and harmonic frequencies of stationary points along the reaction path. Kinetic and dynamical calculations on the PES indicated a good agreement with the available experimental data. PMID- 26671352 TI - Charge-transfer potentials for ionic crystals: Cauchy violation, LO-TO splitting, and the necessity of an ionic reference state. AB - In this work, we study how including charge transfer into force fields affects the predicted elastic and vibrational Gamma-point properties of ionic crystals, in particular those of rock salt. In both analytical and numerical calculations, we find that charge transfer generally leads to a negative contribution to the Cauchy pressure, P(C) = C12 - C66, where C12 and C66 are elements of the elastic tensor. This contribution increases in magnitude with pressure for different charge-transfer approaches in agreement with results obtained with density functional theory (DFT). However, details of the charge-transfer models determine the pressure dependence of the longitudinal optical-transverse optical splitting and that for partial charges. These last two quantities increase with density as long as the chemical hardness depends at most weakly on the environment while experiments and DFT find a decrease. In order to reflect the correct trends, the charge-transfer expansion has to be made around ions and the chemical (bond) hardness has to increase roughly exponentially with inverse density or bond lengths. Finally, the adjustable force-field parameters only turn out meaningful, when the expansion is made around ions. PMID- 26671353 TI - Replica-exchange-with-tunneling for fast exploration of protein landscapes. AB - While the use of replica-exchange molecular dynamics in protein simulations has become ubiquitous, its utility is limited in many practical applications. We propose to overcome some shortcomings that hold back its use in settings such as multi-scale or explicit solvent simulations by integrating ideas of hybrid MC/MD into the replica-exchange protocol. This Replica-Exchange-with-Tunneling method is tested by simulating the Trp-cage protein, a system often used in molecular biophysics for testing sampling techniques. PMID- 26671354 TI - Some studies on generalized coordinate sets for polyatomic molecules. AB - Generalized coordinates are widely used in various analyses of the trajectories of polyatomic molecules from molecular dynamics simulations, such as normal mode analysis and force distribution analysis. Here, we presented detailed discussions on the properties of some specific sets of generalized coordinates, which separate translational, rotational, and vibrational motions of a molecule from one another once the trajectories of dynamical systems are known. Efficient methods were suggested for estimating the transformation matrix between generalized and Cartesian coordinates. Some properties of the well-known BAT coordinates (bond length, angle, and torsional coordinates) were discussed as well. PMID- 26671355 TI - Fermi orbital self-interaction corrected electronic structure of molecules beyond local density approximation. AB - The correction of the self-interaction error that is inherent to all standard density functional theory calculations is an object of increasing interest. In this article, we apply the very recently developed Fermi-orbital based approach for the self-interaction correction [M. R. Pederson et al., J. Chem. Phys. 140, 121103 (2014) and M. R. Pederson, J. Chem. Phys. 142, 064112 (2015)] to a set of different molecular systems. Our study covers systems ranging from simple diatomic to large organic molecules. We focus our analysis on the direct estimation of the ionization potential from orbital eigenvalues. Further, we show that the Fermi orbital positions in structurally similar molecules appear to be transferable. PMID- 26671356 TI - Nonadiabatic dynamics with intersystem crossings: A time-dependent density functional theory implementation. AB - In this work, we derive a method to perform trajectory-based nonadiabatic dynamics that is able to describe both nonadiabatic transitions and intersystem crossing events (transitions between states of different spin-multiplicity) at the same level of theory, namely, time-dependent density functional theory (TDDFT). To this end, we combined our previously developed TDDFT-based trajectory surface hopping scheme with an accurate and efficient algorithm for the calculation of the spin-orbit coupling (SOC) matrix elements. More specifically, we designed two algorithms for the calculation of intersystem crossing transitions, one based on an extended Tully's surface hopping scheme including SOC and the second based on a Landau-Zener approximation applied to the spin sector of the electronic Hilbert space. This development allows for the design of an efficient on-the-fly nonadiabatic approach that can handle, on an equal footing, nonadiabatic and intersystem crossing transitions. The method is applied to the study of the photophysics of sulfur dioxide (SO2) in gas and liquid phases. PMID- 26671357 TI - Exciton size and quantum transport in nanoplatelets. AB - Two-dimensional nanoplatelets (NPLs) are an exciting class of materials with promising optical and energy transport properties. The possibility of efficient energy transport between nanoplatelets raises questions regarding the nature of energy transfer in these thin, laterally extended systems. A challenge in understanding exciton transport is the uncertainty regarding the size of the exciton. Depending on the material and defects in the nanoplatelet, an exciton could plausibly extend over an entire plate or localize to a small region. The variation in possible exciton sizes raises the question how exciton size impacts the efficiency of transport between nanoplatelet structures. Here, we explore this issue using a quantum master equation approach. This method goes beyond the assumptions of Forster theory to allow for quantum mechanical effects that could increase energy transfer efficiency. The model is extremely flexible in describing different systems, allowing us to test the effect of varying the spatial extent of the exciton. We first discuss qualitative aspects of the relationship between exciton size and transport and then conduct simulations of exciton transport between NPLs for a range of exciton sizes and environmental conditions. Our results reveal that exciton size has a strong effect on energy transfer efficiency and suggest that manipulation of exciton size may be useful in designing NPLs for energy transport. PMID- 26671358 TI - Intramolecular symmetry-adapted perturbation theory with a single-determinant wavefunction. AB - We introduce an intramolecular energy decomposition scheme for analyzing non covalent interactions within molecules in the spirit of symmetry-adapted perturbation theory (SAPT). The proposed intra-SAPT approach is based upon the Chemical Hamiltonian of Mayer [Int. J. Quantum Chem. 23(2), 341-363 (1983)] and the recently introduced zeroth-order wavefunction [J. F. Gonthier and C. Corminboeuf, J. Chem. Phys. 140(15), 154107 (2014)]. The scheme decomposes the interaction energy between weakly bound fragments located within the same molecule into physically meaningful components, i.e., electrostatic-exchange, induction, and dispersion. Here, we discuss the key steps of the approach and demonstrate that a single-determinant wavefunction can already deliver a detailed and insightful description of a wide range of intramolecular non-covalent phenomena such as hydrogen bonds, dihydrogen contacts, and pi - pi stacking interactions. Intra-SAPT is also used to shed the light on competing intra- and intermolecular interactions. PMID- 26671359 TI - The mean shape of transition and first-passage paths. AB - Based on the one-dimensional Fokker-Planck equation in an arbitrary free energy landscape including a general inhomogeneous diffusivity profile, we analytically calculate the mean shape of transition paths and first-passage paths, where the shape of a path is defined as the kinetic profile in the plane spanned by the mean time and the position. The transition path ensemble is the collection of all paths that do not revisit the start position x(A) and that terminate when first reaching the final position x(B). In contrast, a first-passage path can revisit its start position x(A) before it terminates at x(B). Our theoretical framework employs the forward and backward Fokker-Planck equations as well as first passage, passage, last-passage, and transition-path time distributions, for which we derive the defining integral equations. We show that the mean shape of transition paths, in other words the mean time at which the transition path ensemble visits an intermediate position x, is equivalent to the mean first passage time of reaching the position x(A) when starting from x without ever visiting x(B). The mean shape of first-passage paths is related to the mean shape of transition paths by a constant time shift. Since for a large barrier height U, the mean first-passage time scales exponentially in U, while the mean transition path time scales linearly inversely in U, the time shift between first-passage and transition path shapes is substantial. We present explicit examples of transition path shapes for linear and harmonic potentials and illustrate our findings by trajectories obtained from Brownian dynamics simulations. PMID- 26671360 TI - Features in chemical kinetics. III. Attracting subspaces in a hyper-spherical representation of the reactive system. AB - In this work, we deal with general reactive systems involving N species and M elementary reactions under applicability of the mass-action law. Starting from the dynamic variables introduced in two previous works [P. Nicolini and D. Frezzato, J. Chem. Phys. 138(23), 234101 (2013); 138(23), 234102 (2013)], we turn to a new representation in which the system state is specified in a (N * M)(2) dimensional space by a point whose coordinates have physical dimension of inverse of-time. By adopting hyper-spherical coordinates (a set of dimensionless "angular" variables and a single "radial" one with physical dimension of inverse of-time) and by examining the properties of their evolution law both formally and numerically on model kinetic schemes, we show that the system evolves towards the equilibrium as being attracted by a sequence of fixed subspaces (one at a time) each associated with a compact domain of the concentration space. Thus, we point out that also for general non-linear kinetics there exist fixed "objects" on the global scale, although they are conceived in such an abstract and extended space. Moreover, we propose a link between the persistence of the belonging of a trajectory to such subspaces and the closeness to the slow manifold which would be perceived by looking at the bundling of the trajectories in the concentration space. PMID- 26671361 TI - Gentlest ascent dynamics for calculating first excited state and exploring energy landscape of Kohn-Sham density functionals. AB - We develop the gentlest ascent dynamics for Kohn-Sham density functional theory to search for the index-1 saddle points on the energy landscape of the Kohn-Sham density functionals. These stationary solutions correspond to excited states in the ground state functionals. As shown by various examples, the first excited states of many chemical systems are given by these index-1 saddle points. Our novel approach provides an alternative, more robust way to obtain these excited states, compared with the widely used DeltaSCF approach. The method can be easily generalized to target higher index saddle points. Our results also reveal the physical interest and relevance of studying the Kohn-Sham energy landscape. PMID- 26671362 TI - General contact mechanics theory for randomly rough surfaces with application to rubber friction. AB - We generalize the Persson contact mechanics and rubber friction theory to the case where both surfaces have surface roughness. The solids can be rigid, elastic, or viscoelastic and can be homogeneous or layered. We calculate the contact area, the viscoelastic contribution to the friction force, and the average interface separation as a function of the sliding speed and the nominal contact pressure. We illustrate the theory with numerical results for the classical case of a rubber block sliding on a road surface. We find that with increasing sliding speed, the influence of the roughness on the rubber block decreases to the extent that only the roughness of the stiff counter face needs to be considered. PMID- 26671363 TI - Extended hierarchy equation of motion for the spin-boson model. AB - An extended hierarchy equation of motion (HEOM) is proposed and applied to study the dynamics of the spin-boson model. In this approach, a complete set of orthonormal functions are used to expand an arbitrary bath correlation function. As a result, a complete dynamic basis set is constructed by including the system reduced density matrix and auxiliary fields composed of these expansion functions, where the extended HEOM is derived for the time derivative of each element. The reliability of the extended HEOM is demonstrated by comparison with the stochastic Hamiltonian approach under room-temperature classical ohmic and sub-ohmic noises and the multilayer multiconfiguration time-dependent Hartree theory under zero-temperature quantum ohmic noise. Upon increasing the order in the hierarchical expansion, the result obtained from the extended HOEM systematically converges to the numerically exact answer. PMID- 26671364 TI - An atomistically informed mesoscale model for growth and coarsening during discharge in lithium-oxygen batteries. AB - An atomistically informed mesoscale model is developed for the deposition of a discharge product in a Li-O2 battery. This mescocale model includes particle growth and coarsening as well as a simplified nucleation model. The model involves LiO2 formation through reaction of O2(-) and Li(+) in the electrolyte, which deposits on the cathode surface when the LiO2 concentration reaches supersaturation in the electrolyte. A reaction-diffusion (rate-equation) model is used to describe the processes occurring in the electrolyte and a phase-field model is used to capture microstructural evolution. This model predicts that coarsening, in which large particles grow and small ones disappear, has a substantial effect on the size distribution of the LiO2 particles during the discharge process. The size evolution during discharge is the result of the interplay between this coarsening process and particle growth. The growth through continued deposition of LiO2 has the effect of causing large particles to grow ever faster while delaying the dissolution of small particles. The predicted size evolution is consistent with experimental results for a previously reported cathode material based on activated carbon during discharge and when it is at rest, although kinetic factors need to be included. The approach described in this paper synergistically combines models on different length scales with experimental observations and should have applications in studying other related discharge processes, such as Li2O2 deposition, in Li-O2 batteries and nucleation and growth in Li-S batteries. PMID- 26671365 TI - Semiclassical initial value representation for the quantum propagator in the Heisenberg interaction representation. AB - One of the challenges facing on-the-fly ab initio semiclassical time evolution is the large expense needed to converge the computation. In this paper, we suggest that a significant saving in computational effort may be achieved by employing a semiclassical initial value representation (SCIVR) of the quantum propagator based on the Heisenberg interaction representation. We formulate and test numerically a modification and simplification of the previous semiclassical interaction representation of Shao and Makri [J. Chem. Phys. 113, 3681 (2000)]. The formulation is based on the wavefunction form of the semiclassical propagation instead of the operator form, and so is simpler and cheaper to implement. The semiclassical interaction representation has the advantage that the phase and prefactor vary relatively slowly as compared to the "standard" SCIVR methods. This improves its convergence properties significantly. Using a one-dimensional model system, the approximation is compared with Herman-Kluk's frozen Gaussian and Heller's thawed Gaussian approximations. The convergence properties of the interaction representation approach are shown to be favorable and indicate that the interaction representation is a viable way of incorporating on-the-fly force field information within a semiclassical framework. PMID- 26671366 TI - Extracting enzyme processivity from kinetic assays. AB - A steady-state analysis for the catalytic turnover of molecules containing two substrate sites is presented. A broad class of Markovian dynamic models, motivated by the action of DNA modifying enzymes and the rich variety of translocation mechanisms associated with these systems (e.g., sliding, hopping, intersegmental transfer, etc.), is considered. The modeling suggests an elementary and general method of data analysis, which enables the extraction of the enzyme's processivity directly and unambiguously from experimental data. This analysis is not limited to the initial velocity regime. The predictions are validated both against detailed numerical models and by revisiting published experimental data for EcoRI endonuclease acting on DNA. PMID- 26671367 TI - Nonlinear electronic excitations in crystalline solids using meta-generalized gradient approximation and hybrid functional in time-dependent density functional theory. AB - We develop methods to calculate electron dynamics in crystalline solids in real time time-dependent density functional theory employing exchange-correlation potentials which reproduce band gap energies of dielectrics; a meta-generalized gradient approximation was proposed by Tran and Blaha [Phys. Rev. Lett. 102, 226401 (2009)] (TBm-BJ) and a hybrid functional was proposed by Heyd, Scuseria, and Ernzerhof [J. Chem. Phys. 118, 8207 (2003)] (HSE). In time evolution calculations employing the TB-mBJ potential, we have found it necessary to adopt the predictor-corrector step for a stable time evolution. We have developed a method to evaluate electronic excitation energy without referring to the energy functional which is unknown for the TB-mBJ potential. For the HSE functional, we have developed a method for the operation of the Fock-like term in Fourier space to facilitate efficient use of massive parallel computers equipped with graphic processing units. We compare electronic excitations in silicon and germanium induced by femtosecond laser pulses using the TB-mBJ, HSE, and a simple local density approximation (LDA). At low laser intensities, electronic excitations are found to be sensitive to the band gap energy: they are close to each other using TB-mBJ and HSE and are much smaller in LDA. At high laser intensities close to the damage threshold, electronic excitation energies do not differ much among the three cases. PMID- 26671368 TI - Structural phase transition causing anomalous photoluminescence behavior in perovskite (C6H11NH3)2[PbI4]. AB - Optical and structural properties of the organic-inorganic hybrid perovskite-type (C6H11NH3)2[PbI4] (abbreviated as C6PbI4) were investigated using optical absorption, photoluminescence (PL), and x-ray diffraction measurements. Room temperature, optical absorption measurements, performed on spin-coated films of C6PbI4, revealed two absorption bands at 2.44 and 3.21 eV. Upon 325 nm (3.815 eV) laser irradiation, strong green PL emission peaks were observed at 2.41 eV (P1) and 2.24 eV (P2) and assigned to free and localized excitons, respectively. The exciton binding energy was estimated at 356 meV. At low temperature, two additional emission bands were detected at 2.366 eV (P3) and a large band (LB) at 1.97 eV. The former appeared only below 40 K and the latter emerged below 130 K. The thermal dependence of the PL spectra revealed an abnormal behavior accompanied by singularities in the peak positions and intensities at 40 and 130 K. X-ray diffraction studies performed on powder and single crystals as a function of temperature evidenced significant changes of the interlayer spacing at 50 K and ~138 K. Around 138 K, a commensurate to incommensurate structural phase transition occurred on cooling. It involves a symmetry breaking leading to a distortion of the PbI6 octahedron. The resulting incommensurate spatial modulation of the Pb-I distances (and Pb-I-Pb angles) causes a spatial modulation of the band gap, which is at the origin of the emergence of the LB below ~130 K and the anomalous behavior of the position of P1 below 130 K. The change of the interlayer spacing in the 40-50 K range may in turn be related to the significant decrease of the intensity of P2 and the maximum emission of the LB. These results underline the intricate character of the structural and the PL properties of the hybrid perovskites; understanding such properties should benefit to the design of optoelectronic devices with targeted properties. PMID- 26671369 TI - Probing microhydration effect on the electronic structure of the GFP chromophore anion: Photoelectron spectroscopy and theoretical investigations. AB - The photophysics of the Green Fluorescent Protein (GFP) chromophore is critically dependent on its local structure and on its environment. Despite extensive experimental and computational studies, there remain many open questions regarding the key fundamental variables that govern this process. One outstanding problem is the role of autoionization as a possible relaxation pathway of the excited state under different environmental conditions. This issue is considered in our work through combined experimental and theoretical studies of microsolvated clusters of the deprotonated p-hydroxybenzylidene-2,3 dimethylimidazolinone anion (HBDI(-)), an analog of the GFP chromophore. Through selective generation of microsolvated structures of predetermined size and subsequent analysis of experimental photoelectron spectra by high level ab initio methods, we are able to precisely identify the structure of the system, establish the accuracy of theoretical data, and provide reliable description of auto ionization process as a function of hydrogen-bonding environment. Our study clearly illustrates the first few water molecules progressively stabilize the excited state of the chromophore anion against the autodetached neutral state, which should be an important trait for crystallographic water molecules in GFPs that has not been fully explored to date. PMID- 26671370 TI - Vibrational corrections to the second hyperpolarizabilities of Al(n)P(n) clusters. AB - In this work, we report results of vibrational corrections to the second hyperpolarizabilities of Al2P2, Al3P3, Al4P4, Al6P6, and Al9P9 clusters. The vibrational corrections were calculated through the perturbation theoretic method of Bishop and Kirtman and also using a variational methodology at the second order Moller-Plesset perturbation theory level with the aug-cc-pVDZ basis set. Results show that the vibrational corrections are important, accounting for more than half of the corresponding electronic second hyperpolarizabilities at the static limit. Comparisons between results obtained through both methods show very good agreements for the terms [alpha(2)] and [MUbeta] but significant differences for the term [MU(2)alpha]. Dynamic vibrational corrections to the second hyperpolarizabilities related to the dc-second harmonic generation, intensity dependent refractive index, and dc-Kerr nonlinear optical processes are also reported. PMID- 26671371 TI - Energy of the quasi-free electron in H2, D2, and O2: Probing intermolecular potentials within the local Wigner-Seitz model. AB - We present for the first time the quasi-free electron energy V0(rho) for H2, D2, and O2 from gas to liquid densities, on noncritical isotherms and on a near critical isotherm in each fluid. These data illustrate the ability of field enhanced photoemission (FEP) to determine V0(rho) accurately in strongly absorbing fluids (e.g., O2) and fluids with extremely low critical temperatures (e.g., H2 and D2). We also show that the isotropic local Wigner-Seitz model for V0(rho)--when coupled with thermodynamic data for the fluid--can yield optimized parameters for intermolecular potentials, as well as zero kinetic energy electron scattering lengths. PMID- 26671372 TI - Excitation of vibrational quanta in furfural by intermediate-energy electrons. AB - We report cross sections for electron-impact excitation of vibrational quanta in furfural, at intermediate incident electron energies (20, 30, and 40 eV). The present differential cross sections are measured over the scattered electron angular range 10 degrees -90 degrees , with corresponding integral cross sections subsequently being determined. Furfural is a viable plant-derived alternative to petrochemicals, being produced via low-temperature plasma treatment of biomass. Current yields, however, need to be significantly improved, possibly through modelling, with the present cross sections being an important component of such simulations. To the best of our knowledge, there are no other cross sections for vibrational excitation of furfural available in the literature, so the present data are valuable for this important molecule. PMID- 26671373 TI - Infrared spectroscopic investigation of nuclear spin conversion in solid CH4. AB - Infrared spectra of solid CH4 were studied in the nu3 and nu4 vibrational regions. The phase I crystal around 30 K showed broad absorption bands, whereas the phase II crystal at 6.9-10.3 K exhibited splitting of these bands after annealing above 20 K. The split peaks were assigned to the librating and almost freely rotating molecules in phase II on the basis of the peak spacings and time evolution of the peak intensities. From the quantitative analysis of the temporal changes of the R(0) and R(1) peak intensities, the relaxation rates of the numbers of molecules with J = 0 (I = 2) and J = 1 (I = 1) were determined in the temperature range of 6.9-10.3 K. We fitted the function resulting from a combination of direct and indirect relaxation processes mediated by phonons to the temperature dependence of these rates and obtained the activation energies of the indirect process: C ? 36 K. Since this value is higher than the energies of perturbed J = 2 states relative to the J = 1 state, we argue that the nuclear spin conversion through the J = 3 state also takes place. PMID- 26671374 TI - Coronene molecules in helium clusters: Quantum and classical studies of energies and configurations. AB - Coronene-doped helium clusters have been studied by means of classical and quantum mechanical (QM) methods using a recently developed He-C24H12 global potential based on the use of optimized atom-bond improved Lennard-Jones functions. Equilibrium energies and geometries at global and local minima for systems with up to 69 He atoms were calculated by means of an evolutive algorithm and a basin-hopping approach and compared with results from path integral Monte Carlo (PIMC) calculations at 2 K. A detailed analysis performed for the smallest sizes shows that the precise localization of the He atoms forming the first solvation layer over the molecular substrate is affected by differences between relative potential minima. The comparison of the PIMC results with the predictions from the classical approaches and with diffusion Monte Carlo results allows to examine the importance of both the QM and thermal effects. PMID- 26671375 TI - Hyperpolarizability dispersion measured for (CH3)2O. AB - The third-order nonlinear-optical susceptibility of dimethyl ether, (CH3)2O, has been measured in the gas phase over the wavelength range 488 nm < lambda < 1064 nm using the technique of gas-phase electric-field-induced second-harmonic generation with periodic phase matching and with N2 as the reference gas. Measurements span a range of temperature, which allows for separation of the temperature-independent second hyperpolarizability term from the temperature dependent first hyperpolarizability term. The dispersion curves of the isotropically averaged first and second hyperpolarizabilities (beta and gamma) are deduced. PMID- 26671376 TI - Optical-optical double resonance, laser induced fluorescence, and revision of the signs of the spin-spin constants of the boron carbide (BC) free radical. AB - The cold boron carbide free radical (BC X (4)Sigma(-)) has been produced in a pulsed discharge free jet expansion using a precursor mixture of trimethylborane in high pressure argon. High resolution laser induced fluorescence spectra have been obtained for the B (4)Sigma(-)-X (4)Sigma(-) and E (4)Pi-X (4)Sigma(-) band systems of both (11)BC and (10)BC. An optical-optical double resonance (OODR) scheme was implemented to study the finer details of both band systems. This involved pumping a single rotational level of the B state with one laser and then recording the various allowed transitions from the intermediate B state to the final E state with a second laser by monitoring the subsequent E-X ultraviolet fluorescence. In this fashion, we were able to prove unambiguously that, contrary to previous studies, the spin-spin constant lambda is negative in the ground state and positive in the B (4)Sigma(-) excited state. It has been shown that lambda" < 0 is in fact expected based on a semiempirical second order perturbation theory calculation of the magnitude of the spin-spin constant. The OODR spectra have also been used to validate our assignments of the complex and badly overlapped E (4)Pi-X (4)Sigma(-) 0-0 and 1-0 bands of (11)BC. The E-X 0-0 band of (10)BC was found to be severely perturbed. The ground state main electron configuration is ...3sigma(2)4sigma(2)5sigma(1)1pi(2)2pi(0) and the derived bond lengths show that there is a 0.03 A contraction in the B state, due to the promotion of an electron from the 4sigma antibonding orbital to the 5sigma bonding orbital. In contrast, the bond length elongates by 0.15 A in the E state, a result of promoting an electron from the 5sigma bonding orbital to the 2pi antibonding orbitals. PMID- 26671377 TI - Laser-induced dissociation dynamics of triatomic molecule in electronic excited states: A full-dimensional quantum mechanics study. AB - We present a detailed theoretical approach to investigate the laser-induced dissociation dynamics of a triatomic molecule on its electronic excited state in full dimensional case. In this method, the time evolution of the time-dependent system is propagated via combined the split operator method and the expansion of Chebyshev polynomials (or short-time Chebyshev propagation) and the system wave functions are expanded in terms of molecular rotational bases. As an example of the application of this formalism, the dissociation dynamics of H3(+)->H2(+)+H induced by ultrashort UV laser pulses are investigated on new Born-Oppenheimer potential energy surfaces. Our numerical results show that the signals of dissociation products will be easier to observe as the increasing of field strength. Driving by a 266 nm laser beam, the calculated central value of kinetic energy-release is 2.04 eV which shows excellent agreement with the experimental estimation of 2.1 eV. When the H3(+) ion is rotationally excited, the spatial distribution of product fragments will become well converged. PMID- 26671378 TI - Interatomic Coulombic decay widths of helium trimer: Ab initio calculations. AB - We report on an extensive study of interatomic Coulombic decay (ICD) widths in helium trimer computed using a fully ab initio method based on the Fano theory of resonances. Algebraic diagrammatic construction for one-particle Green's function is utilized for the solution of the many-electron problem. An advanced and universal approach to partitioning of the configuration space into discrete states and continuum subspaces is described and employed. Total decay widths are presented for all ICD-active states of the trimer characterized by one-site ionization and additional excitation of an electron into the second shell. Selected partial decay widths are analyzed in detail, showing how three-body effects can qualitatively change the character of certain relaxation transitions. Previously unreported type of three-electron decay processes is identified in one class of the metastable states. PMID- 26671379 TI - Vibrational investigations of CO2-H2O, CO2-(H2O)2, and (CO2)2-H2O complexes isolated in solid neon. AB - The van der Waals complex of H2O with CO2 has attracted considerable theoretical interest as a typical example of a weak binding complex with a dissociation energy less than 3 kcal/mol. Up to now, experimental vibrational data are sparse. We have studied by FTIR the complexes involving CO2 and water molecules in solid neon. Many new absorption bands close to the well known monomers fundamentals give evidence for at least three (CO2)n-(H2O)m complexes, noted n:m. Concentration effects combined with a detailed vibrational analysis allow for the identification of sixteen, twelve, and five transitions for the 1:1, 1:2, and 2:1 complexes, respectively. Careful examination of the far infrared spectral region allows the assignment of several 1:1 and 1:2 intermolecular modes, confirmed by the observation of combinations of intra + intermolecular transitions, and anharmonic coupling constants have been derived. Our results demonstrate the high sensibility of the solid neon isolation to investigate the hydrogen-bonded complexes in contrast with the gas phase experiments for which two quanta transitions cannot be easily observed. PMID- 26671380 TI - The determination of potential energy curve and dipole moment of the (5)0(+) electronic state of (85)Rb(133)Cs molecule by high resolution photoassociation spectroscopy. AB - We present the formation of ultracold (85)Rb(133)Cs molecules in the (5)0(+) electronic state by photoassociation and their detection via resonance-enhanced two-photon ionization. Up to v = 47 vibrational levels including the lowest v = 0 vibrational and lowest J = 0 levels are identified with rotationally resolved high resolution photoassociation spectra. Precise Dunham coefficients are determined for the (5)0(+) state with high accuracy, then the Rydberg-Klein-Rees potential energy curve is derived. The electric dipole moments with respect to the vibrational numbers of the (5)0(+) electronic state of (85)Rb(133)Cs molecule are also measured in the range between 1.9 and 4.8 D. These comprehensive studies on previously unobserved rovibrational levels of the (5)0(+) state are helpful to understand the molecular structure and discover suitable transition pathways for transferring ultracold atoms to deeply bound rovibrational levels of the electronic ground state. PMID- 26671381 TI - Thermal radiation and fragmentation pathways of photo-excited silicon clusters. AB - The fragmentation of laser heated silicon clusters was studied by time-of-flight mass spectrometry. For Si(n)(+) (n = 5-19, 21), the lowest energy fragmentation pathways were identified as the metastable decay channel occurring after the primary acceleration of the ions. The radiative cooling of laser excited Si(n)(+) (n = 5-9, 11, and 13) was quantified via its quenching effect on the amount of metastable fragmentation. The quenching varied strongly with cluster size, from no observable amount for Si7(+) to a cooling constant of 3 ? 10(5) s(-1) for Si13(+). In addition, based on the observed fragmentation channels, the ionization energies and the relative binding energies of the clusters were partially ordered, and several ionization energies have been bracketed more precisely. PMID- 26671382 TI - The anharmonic quartic force field infrared spectra of three polycyclic aromatic hydrocarbons: Naphthalene, anthracene, and tetracene. AB - Current efforts to characterize and study interstellar polycyclic aromatic hydrocarbons (PAHs) rely heavily on theoretically predicted infrared (IR) spectra. Generally, such studies use the scaled harmonic frequencies for band positions and double harmonic approximation for intensities of species, and then compare these calculated spectra with experimental spectra obtained under matrix isolation conditions. High-resolution gas-phase experimental spectroscopic studies have recently revealed that the double harmonic approximation is not sufficient for reliable spectra prediction. In this paper, we present the anharmonic theoretical spectra of three PAHs: naphthalene, anthracene, and tetracene, computed with a locally modified version of the SPECTRO program using Cartesian derivatives transformed from Gaussian 09 normal coordinate force constants. Proper treatments of Fermi resonances lead to an impressive improvement on the agreement between the observed and theoretical spectra, especially in the C-H stretching region. All major IR absorption features in the full-scale matrix-isolated spectra, the high-temperature gas-phase spectra, and the most recent high-resolution gas-phase spectra obtained under supersonically cooled molecular beam conditions in the CH-stretching region are assigned. PMID- 26671383 TI - Spectroscopic identification of ethanol-water conformers by large-amplitude hydrogen bond librational modes. AB - The far-infrared absorption spectra have been recorded for hydrogen-bonded complexes of water with ethanol embedded in cryogenic neon matrices at 2.8 K. The partial isotopic H/D-substitution of the ethanol subunit enabled by a dual inlet deposition procedure enables the observation and unambiguous assignment of the intermolecular high-frequency out-of-plane and the low-frequency in-plane donor OH librational modes for two different conformations of the mixed binary ethanol/water complex. The resolved donor OH librational bands confirm directly previous experimental evidence that ethanol acts as the O?HO hydrogen bond acceptor in the two most stable conformations. In the most stable conformation, the water subunit forces the ethanol molecule into its less stable gauche configuration upon dimerization owing to a cooperative secondary weak O?HC hydrogen bond interaction evidenced by a significantly blue-shift of the low frequency in-plane donor OH librational band origin. The strong correlation between the low-frequency in-plane donor OH librational motion and the secondary intermolecular O?HC hydrogen bond is demonstrated by electronic structure calculations. The experimental findings are further supported by CCSD(T)-F12/aug cc-pVQZ calculations of the conformational energy differences together with second-order vibrational perturbation theory calculations of the large-amplitude donor OH librational band origins. PMID- 26671384 TI - Understanding the nonlinear dynamics of driven particles in supercooled liquids in terms of an effective temperature. AB - In active microrheology, the mechanical properties of a material are tested by adding probe particles which are pulled by an external force. In case of supercooled liquids, strong forcing leads to a thinning of the host material which becomes more pronounced as the system approaches the glass transition. In this work, we provide a quantitative theoretical description of this thinning behavior based on the properties of the Potential Energy Landscape (PEL) of a model glass-former. A key role plays the trap-like nature of the PEL. We find that the mechanical properties in the strongly driven system behave the same as in a quiescent system at an enhanced temperature, giving rise to a well characterized effective temperature. Furthermore, this effective temperature turns out to be independent of the chosen observable and individually shows up in the thermodynamic and dynamic properties of the system. Based on this underlying theoretical understanding, we can estimate its dependence on temperature and force by the PEL-properties of the quiescent system. We furthermore critically discuss the relevance of effective temperatures obtained by scaling relations for the description of out-of-equilibrium situations. PMID- 26671385 TI - A molecularly based theory for electron transfer reorganization energy. AB - Using field-theoretic techniques, we develop a molecularly based dipolar self consistent-field theory (DSCFT) for charge solvation in pure solvents under equilibrium and nonequilibrium conditions and apply it to the reorganization energy of electron transfer reactions. The DSCFT uses a set of molecular parameters, such as the solvent molecule's permanent dipole moment and polarizability, thus avoiding approximations that are inherent in treating the solvent as a linear dielectric medium. A simple, analytical expression for the free energy is obtained in terms of the equilibrium and nonequilibrium electrostatic potential profiles and electric susceptibilities, which are obtained by solving a set of self-consistent equations. With no adjustable parameters, the DSCFT predicts activation energies and reorganization energies in good agreement with previous experiments and calculations for the electron transfer between metallic ions. Because the DSCFT is able to describe the properties of the solvent in the immediate vicinity of the charges, it is unnecessary to distinguish between the inner-sphere and outer-sphere solvent molecules in the calculation of the reorganization energy as in previous work. Furthermore, examining the nonequilibrium free energy surfaces of electron transfer, we find that the nonequilibrium free energy is well approximated by a double parabola for self-exchange reactions, but the curvature of the nonequilibrium free energy surface depends on the charges of the electron transferring species, contrary to the prediction by the linear dielectric theory. PMID- 26671386 TI - Vibrational properties of organic donor-acceptor molecular crystals: Anthracene pyromellitic-dianhydride (PMDA) as a case study. AB - We establish a reliable quantum-mechanical approach to evaluate the vibrational properties of donor-acceptor molecular crystals. The anthracene-PMDA (PMDA = pyromellitic dianhydride) crystal, where anthracene acts as the electron donor and PMDA as the electron acceptor, is taken as a representative system for which experimental non-resonance Raman spectra are also reported. We first investigate the impact that the amount of nonlocal Hartree-Fock exchange (HFE) included in a hybrid density functional has on the geometry, normal vibrational modes, electronic coupling, and electron-vibrational (phonon) couplings. The comparison between experimental and theoretical Raman spectra indicates that the results based on the alphaPBE functional with 25%-35% HFE are in better agreement with the experimental results compared to those obtained with the pure PBE functional. Then, taking alphaPBE with 25% HFE, we assign the vibrational modes and examine their contributions to the relaxation energy related to the nonlocal electron vibration interactions. The results show that the largest contribution (about 90%) is due to electron interactions with low-frequency vibrational modes. The relaxation energy in anthracene-PMDA is found to be about five times smaller than the electronic coupling. PMID- 26671387 TI - Dual reorientation relaxation routes of water molecules in oxyanion's hydration shell: A molecular geometry perspective. AB - In this study, we examine how complex ions such as oxyanions influence the dynamic properties of water and whether differences exist between simple halide anions and oxyanions. Nitrate anion is taken as an example to investigate the hydration properties of oxyanions. Reorientation relaxation of its hydration water can occur through two different routes: water can either break its hydrogen bond with the nitrate to form one with another water or switch between two oxygen atoms of the same nitrate. The latter molecular mechanism increases the residence time of oxyanion's hydration water and thus nitrate anion slows down the translational motion of neighbouring water. But it is also a "structure breaker" in that it accelerates the reorientation relaxation of hydration water. Such a result illustrates that differences do exist between the hydration of oxyanions and simple halide anions as a result of different molecular geometries. Furthermore, the rotation of the nitrate solute is coupled with the hydrogen bond rearrangement of its hydration water. The nitrate anion can either tilt along the axis perpendicularly to the plane or rotate in the plane. We find that the two reorientation relaxation routes of the hydration water lead to different relaxation dynamics in each of the two above movements of the nitrate solute. The current study suggests that molecular geometry could play an important role in solute hydration and dynamics. PMID- 26671388 TI - Effect of the cation model on the equilibrium structure of poly-L-glutamate in aqueous sodium chloride solution. AB - We demonstrate that different sets of Lennard-Jones parameters proposed for the Na(+) ion, in conjunction with the empirical combining rules routinely used in simulation packages, can lead to essentially different equilibrium structures for a deprotonated poly-L-glutamic acid molecule (poly-L-glutamate) dissolved in a 0.3M aqueous NaCl solution. It is, however, difficult to discriminate a priori between these model potentials; when investigating the structure of the Na(+) solvation shell in bulk NaCl solution, all parameter sets lead to radial distribution functions and solvation numbers in broad agreement with the available experimental data. We do not find any such dependency of the equilibrium structure on the parameters associated with the Cl(-) ion. This work does not aim at recommending a particular set of parameters for any particular purpose. Instead, it stresses the model dependence of simulation results for complex systems such as biomolecules in solution and thus the difficulties if simulations are to be used for unbiased predictions, or to discriminate between contradictory experiments. However, this opens the possibility of validating a model specifically in view of analyzing experimental data believed to be reliable. PMID- 26671389 TI - Hard convex lens-shaped particles: Densest-known packings and phase behavior. AB - By using theoretical methods and Monte Carlo simulations, this work investigates dense ordered packings and equilibrium phase behavior (from the low-density isotropic fluid regime to the high-density crystalline solid regime) of monodisperse systems of hard convex lens-shaped particles as defined by the volume common to two intersecting congruent spheres. We show that, while the overall similarity of their shape to that of hard oblate ellipsoids is reflected in a qualitatively similar phase diagram, differences are more pronounced in the high-density crystal phase up to the densest-known packings determined here. In contrast to those non-(Bravais)-lattice two-particle basis crystals that are the densest-known packings of hard (oblate) ellipsoids, hard convex lens-shaped particles pack more densely in two types of degenerate crystalline structures: (i) non-(Bravais)-lattice two-particle basis body-centered-orthorhombic-like crystals and (ii) (Bravais) lattice monoclinic crystals. By stacking at will, regularly or irregularly, laminae of these two crystals, infinitely degenerate, generally non-periodic in the stacking direction, dense packings can be constructed that are consistent with recent organizing principles. While deferring the assessment of which of these dense ordered structures is thermodynamically stable in the high-density crystalline solid regime, the degeneracy of their densest-known packings strongly suggests that colloidal convex lens-shaped particles could be better glass formers than colloidal spheres because of the additional rotational degrees of freedom. PMID- 26671390 TI - Ice friction: Role of non-uniform frictional heating and ice premelting. AB - The low friction of ice is usually attributed to the formation of a thin water film due to melting of ice by frictional heating. Melting of ice is a first order phase transition where physical quantities like mass density, the elastic modulus or the shear strength changes abruptly at the transition temperature. Thus, one may expect the friction coefficient to change abruptly at some characteristic sliding speed, when the melt water film is produced. We show that taking into account that, due to non-uniform frictional heating, melting does not occur simultaneously in all the ice contact regions, the transition is not abrupt but still more rapid (as a function of sliding speed) than observed experimentally. The slower than expected drop in the friction with increasing sliding speed may be a consequence of the following paradoxical phenomena: before the melt-water film is formed, the friction of ice is high and a large frictional heating occur which may result in the melting of the ice. If a thin (nanometer) water film would form, the friction becomes low which results in small frictional heating and the freezing of the water film. This suggests a region in sliding speed where a thin (nanometer) surface layer of the ice may be in a mixed state with small ice-like and water-like domains, which fluctuate rapidly in space and time. Alternatively, and more likely, heat-softening of the ice may occur resulting in a thin, statistically homogeneous (in the lateral direction) layer of disordered ice, with a shear strength which decreases continuously as the ice surface temperature approaches the bulk melting temperature. This layer could be related to surface premelting of ice. Using a phenomenological expression for the frictional shear stress, I show that the calculated ice friction is in good agreement with experimental observations. PMID- 26671391 TI - Ordered heteromolecular overlayers formed by metal phthalocyanines and porphyrins on rutile titanium dioxide surface studied at room temperature. AB - Molecular heterostructures are formed from meso-tetraphenyl porphyrins-Zn(II) (ZnTPP) and Cu(II)-phthalocyanines (CuPc) on the rutile TiO2(011) surface. We demonstrate that ZnTPP molecules form a quasi-ordered wetting layer with flat lying molecules, which provides the support for growth of islands comprised of upright CuPc molecules. The incorporation of the ZnTPP layer and the growth of heterostructures increase the stability of the system and allow for room temperature scanning tunneling microscopy (STM) measurements, which is contrasted with unstable STM probing of only CuPc species on TiO2. We demonstrate that within the CuPc layer the molecules arrange in two phases and we identify molecular dimers as basic building blocks of the dominant structural phase. PMID- 26671392 TI - Defect induced d(0) ferromagnetism in a ZnO grain boundary. AB - Several experimental studies have referred to the grain boundary (GB) defect as the origin of ferromagnetism in zinc oxide (ZnO). However, the mechanism of this hypothesis has never been confirmed. Present study investigates the atomic structure and the effect of point defects in a ZnO GB using the generalized gradient approximation+U approximation. The relaxed GB possesses large periodicity and channels with 8 and 10 numbered atoms having 4 and 3 fold coordination. The Zn vacancy (V(Zn)) shows a tendency to be attracted to the GB, relative to the bulk-like region. Although no magnetization is obtained from point defect-free GB, V(Zn) induces spin polarization as large as 0.68 MU(B)/atom to the O sites at the GB. Ferromagnetic exchange energy >150 eV is obtained by increasing the concentration of V(Zn) and by the injection of holes into the system. Electronic structure analysis indicates that the spin polarization without external dopants originates from the O 2p orbitals, a common feature of d(0) semiconductors. PMID- 26671394 TI - Universal low-frequency asymptotes of dynamic conic nanopore rectification: An ionic nanofluidic inductor. AB - We report the first nanofluidic inductor (L) to complement the known nanofluidic capacitors (C), resistors (R), and diodes for ion currents. Under negative bias, the nanopore behaves like a parallel RC circuit at low frequencies; however, under positive bias, the asymptotic dynamics is that of a serial RL circuit. This new ionic circuit element can lead to nanofluidic RLC or diode-inductor oscillator circuits and new intrapore biosensing/rapid sequencing strategies. A universal theory, with explicit estimates for the capacitance and inductance at opposite biases, is derived to collapse the rectified dynamics of all conic nanopores to facilitate design of this new nanofluidic circuit. PMID- 26671393 TI - Linking the HOMO-LUMO gap to torsional disorder in P3HT/PCBM blends. AB - The electronic structure of [6,6]-phenyl C61 butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segments in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando. PMID- 26671395 TI - Ion current rectification in funnel-shaped nanochannels: Hysteresis and inversion effects. AB - Ion current rectification inversion is observed in a funnel-shaped nanochannel above a threshold voltage roughly corresponding to the under-limiting to over limiting current transition. Previous experimental studies have examined rectification at either low-voltages (under-limiting current region) for conical nanopores/funnel-shaped nanochannels or at high-voltages (over-limiting region) for straight nanochannels with asymmetric entrances or asymmetric interfacing microchannels. The observed rectification inversion occurs because the system resistance is shifted, beyond a threshold voltage, from being controlled by intra channel ion concentration-polarization to that controlled by external concentration-polarization. Additionally, strong hysteresis effects, due to residual concentration-polarization, manifest themselves through the dependence of the transient current rectification on voltage scan rate. PMID- 26671396 TI - Towards a systematic assessment of errors in diffusion Monte Carlo calculations of semiconductors: Case study of zinc selenide and zinc oxide. AB - The fixed node diffusion Monte Carlo (DMC) method has attracted interest in recent years as a way to calculate properties of solid materials with high accuracy. However, the framework for the calculation of properties such as total energies, atomization energies, and excited state energies is not yet fully established. Several outstanding questions remain as to the effect of pseudopotentials, the magnitude of the fixed node error, and the size of supercell finite size effects. Here, we consider in detail the semiconductors ZnSe and ZnO and carry out systematic studies to assess the magnitude of the energy differences arising from controlled and uncontrolled approximations in DMC. The former include time step errors and supercell finite size effects for ground and optically excited states, and the latter include pseudopotentials, the pseudopotential localization approximation, and the fixed node approximation. We find that for these compounds, the errors can be controlled to good precision using modern computational resources and that quantum Monte Carlo calculations using Dirac-Fock pseudopotentials can offer good estimates of both cohesive energy and the gap of these systems. We do however observe differences in calculated optical gaps that arise when different pseudopotentials are used. PMID- 26671397 TI - Wetting and dewetting of narrow hydrophobic channels by orthogonal electric fields: Structure, free energy, and dynamics for different water models. AB - Wetting and dewetting of a (6,6) carbon nanotube in presence of an orthogonal electric field of varying strengths are studied by means of molecular dynamics simulations using seven different models of water. We have looked at filling of the channel, occupancy and structure of water inside it, associated free energy profiles, and also dynamical properties like the time scales of collective dipole flipping and residence dynamics. For the current systems where the entire simulation box is under the electric field, the nanotube is found to undergo electrodrying, i.e., transition from filled to empty states on increase of the electric field. The free energy calculations show that the empty state is the most stable one at higher electric field as it raptures the hydrogen bond environment inside the carbon nanotube by reorienting water molecules to its direction leading to a depletion of water molecules inside the channel. We investigated the collective flipping of water dipoles inside the channel and found that it follows a fast stepwise mechanism. On the dynamical side, the dipole flipping is found to occur at a faster rate with increase of the electric field. Also, the rate of water flow is found to decrease dramatically as the field strength is increased. The residence time of water molecules inside the channel is also found to decrease with increasing electric field. Although the effects of electric field on different water models are found to be qualitatively similar, the quantitative details can be different for different models. In particular, the dynamics of water molecules inside the channel can vary significantly for different water models. However, the general behavior of wetting and dewetting transitions, enhanced dipole flips, and shorter residence times on application of an orthogonal electric field hold true for all water models considered in the current work. PMID- 26671398 TI - Pair mobility functions for rigid spheres in concentrated colloidal dispersions: Force, torque, translation, and rotation. AB - The formulation of detailed models for the dynamics of condensed soft matter including colloidal suspensions and other complex fluids requires accurate description of the physical forces between microstructural constituents. In dilute suspensions, pair-level interactions are sufficient to capture hydrodynamic, interparticle, and thermodynamic forces. In dense suspensions, many body interactions must be considered. Prior analytical approaches to capturing such interactions such as mean-field approaches replace detailed interactions with averaged approximations. However, long-range coupling and effects of concentration on local structure, which may play an important role in, e.g., phase transitions, are smeared out in such approaches. An alternative to such approximations is the detailed modeling of hydrodynamic interactions utilizing precise couplings between moments of the hydrodynamic traction on a suspended particle and the motion of that or other suspended particles. For two isolated spheres, a set of these functions was calculated by Jeffrey and Onishi [J. Fluid Mech. 139, 261-290 (1984)] and Jeffrey [J. Phys. Fluids 4, 16-29 (1992)]. Along with pioneering work by Batchelor, these are the touchstone for low-Reynolds number hydrodynamic interactions and have been applied directly in the solution of many important problems related to the dynamics of dilute colloidal dispersions [G. K. Batchelor and J. T. Green, J. Fluid Mech. 56, 375-400 (1972) and G. K. Batchelor, J. Fluid Mech. 74, 1-29 (1976)]. Toward extension of these functions to concentrated systems, here we present a new stochastic sampling technique to rapidly calculate an analogous set of mobility functions describing the hydrodynamic interactions between two hard spheres immersed in a suspension of arbitrary concentration, utilizing accelerated Stokesian dynamics simulations. These mobility functions provide precise, radially dependent couplings of hydrodynamic force and torque to particle translation and rotation, for arbitrary colloid volume fraction phi. The pair mobilities (describing entrainment of one particle by the disturbance flow created by another) decay slowly with separation distance: as 1/r, for volume fractions 0.05 <= phi <= 0.5. For the relative mobility, we find an initially rapid growth as a pair separates, followed by a slow, 1/r growth. Up to phi <= 0.4, the relative mobility does not reached the far-field value even beyond separations of many particle sizes. In the case of phi = 0.5, the far-field asymptote is reached but only at a separation of eight radii and after a slow 1/r growth. At these higher concentrations, the coefficients also reveal liquid-like structural effects on pair mobility at close separations. These results confirm that long-range many-body hydrodynamic interactions are an essential part of the dynamics of concentrated systems and that care must be taken when applying renormalization schemes. PMID- 26671399 TI - Temperature dependence of Soret and diffusion coefficients for toluene cyclohexane mixture measured in convection-free environment. AB - We report on the measurement of diffusion (D), Soret (S(T)), and thermodiffusion (D(T)) coefficients in toluene-cyclohexane mixture with mass fraction of toluene 0.40 onboard of the International Space Station. The coefficients were measured in the range of the mean temperatures between 20 degrees C and 34 degrees C. The Soret coefficient is negative within the investigated temperature range and its absolute value |S(T)| decreases with increasing temperature. The diffusion coefficient for this system increases with temperature rising. For comparison, the temperature dependence of diffusion coefficient was measured in ground laboratory using counter-flow cell technique and revealed a good agreement with microgravity results. A non-direct comparison of the measured onboard Soret coefficients with different systems indicated a similar trend for the temperature dependent behavior. Unexpected experimental finding is that for this system the thermodiffusion coefficient D(T) does not depend on temperature. PMID- 26671400 TI - Brush in the bath of active particles: Anomalous stretching of chains and distribution of particles. AB - The interaction between polymer brush and colloidal particles has been intensively studied in the last two decades. Here, we consider a flat chain grafted substrate immersed in a bath of active particles. Simulations show that an increase in the self-propelling force causes an increase in the number of particles that penetrate into the brush. Anomalously, the particle density inside the main body of the brush eventually becomes higher than that outside the brush at very large self-propelling force. The grafted chains are further stretched due to the steric repulsion from the intruded particles. Upon the increase of the self-propelling force, distinct stretching behaviors of the chains were observed for low and high grafting densities. Surprisingly, we find a weak descent of the average end-to-end distance of chains at high grafting density and very large force which is reminiscent of the compression effect of a chain in the active bath. PMID- 26671401 TI - Kinetics of swelling of polyelectrolyte gels: Fixed degree of ionization. AB - The swelling kinetics of uncharged and charged polymer (polyelectrolyte) gels in salt-free conditions is studied in one dimension by solving the constitutive equation of motion (Newton's law for the elementary gel volume) of the displacement variable by two theoretical methods: one in which the classical definition of stress is used with the bulk modulus taken as a parameter, and the other in which a phenomenological expression of the osmotic stress as a function of polymer density and degree of ionization is taken as an input to the dynamics. The time-evolution profiles for spatially varying polymer density and stress, along with the location of the gel-solvent interface, are obtained from the two methods. We show that both the polymer density (volume fraction) and stress inside the gel follow expected behaviours of being maximum for the uniformly shrunken gel, and relaxing slowly to the lowest values as the gel approaches equilibrium. We further show that, by comparing the temporal profiles of the gel solvent interface and other variables between the two methods, one may attempt to assign an effective bulk modulus to the polyelectrolyte gel as a function of the degree of ionization and other parameters of the gel such as hydrophobicity, cross-link density, and the temperature. The major result we get is that the effective bulk modulus of a polyelectrolyte gel increases monotonically with its degree of ionization. In the process of identifying the parameters for a monotonic swelling, we calculated using a well-known expression of the free energy the equilibrium results of two-phase co-existence and the critical point of a polyelectrolyte gel with a fixed degree of ionization. PMID- 26671402 TI - Effects of degree of freedom below entanglement segment on relaxation of polymer configuration under fast shear in multi-chain slip-spring simulations. AB - In spite of lots of attempts, polymer dynamics under fast flow still remains unrevealed. One of the unsolved issues is the insensitivity of end-to-end relaxation of entangled polymers to shear reported by Watanabe et al. [Macromolecules 35, 8802 (2002)] and recently re-examined by Horio et al. [Macromolecules 47, 246 (2014)]. In this study, the effects of degree of freedom below entanglement segment were investigated on the polymer dynamics by the modified multi-chain slip-spring model. The model was validated through the consistency with earlier simulations and experiments for the shear rate dependence of viscosity, end-to-end dimension projected in the shear gradient direction, entanglement density, and anisotropic diffusion tensor. However, the end-to-end relaxation is accelerated under fast shear to follow the earlier multi chain slip-link model and modified tube model simulations. The results are insensitive to the number of beads between entanglements, supporting the validity of further coarse-grained models. Nevertheless, the flow insensitivity of end-to end relaxation of entangled linear chains has remained unsolved. PMID- 26671403 TI - Exploring the stochastic dynamics of correlated movement of receptor proteins in plasma membranes in vivo. AB - Ligand-induced receptor dimerization plays a crucial role in the signaling process of living cells. In this study, we developed a theoretical model and performed single-molecule tracking to explore the correlated diffusion processes of liganded epidermal growth factor receptors prior to dimer formation. We disclosed that both an attractive potential between liganded receptor proteins in proximity and correlated fluctuations in the local environments of the proteins play an important role to produce the observed correlated movement of the receptors. This result can serve as the foundation to shed light on the way in which receptor functions are regulated in plasma membranes in vivo. PMID- 26671404 TI - Electronic coupling through natural amino acids. AB - Myriad scientific domains concern themselves with biological electron transfer (ET) events that span across vast scales of rate and efficiency through a remarkably fine-tuned integration of amino acid (AA) sequences, electronic structure, dynamics, and environment interactions. Within this intricate scheme, many questions persist as to how proteins modulate electron-tunneling properties. To help elucidate these principles, we develop a model set of peptides representing the common alpha-helix and beta-strand motifs including all natural AAs within implicit protein-environment solvation. Using an effective Hamiltonian strategy with density functional theory, we characterize the electronic coupling through these peptides, furthermore considering side-chain dynamics. For both motifs, predictions consistently show that backbone-mediated electronic coupling is distinctly sensitive to AA type (aliphatic, polar, aromatic, negatively charged and positively charged), and to side-chain orientation. The unique properties of these residues may be employed to design activated, deactivated, or switch-like superexchange pathways. Electronic structure calculations and Green's function analyses indicate that localized shifts in the electron density along the peptide play a role in modulating these pathways, and further substantiate the experimentally observed behavior of proline residues as superbridges. The distinct sensitivities of tunneling pathways to sequence and conformation revealed in this electronic coupling database help improve our fundamental understanding of the broad diversity of ET reactivity and provide guiding principles for peptide design. PMID- 26671405 TI - Note: Boundary homogenization for a circle with periodic absorbing arcs. Exact expression for the effective trapping rate. PMID- 26671406 TI - Erratum: "Comparing thermal wave function methods for multi-configuration time dependent Hartree simulations" [J. Chem. Phys. 140, 044106 (2014)]. PMID- 26671407 TI - Publisher's Note: "The role of non-specific interactions in a patchy model of protein crystallization" [J. Chem. Phys. 143, 194511 (2015)]. PMID- 26671409 TI - Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. AB - With the number of prognostic and predictive genetic markers in neuro-oncology steadily growing, the need for comprehensive molecular analysis of neuropathology samples has vastly increased. We therefore developed a customized enrichment/hybrid-capture-based next-generation sequencing (NGS) gene panel comprising the entire coding and selected intronic and promoter regions of 130 genes recurrently altered in brain tumors, allowing for the detection of single nucleotide variations, fusions, and copy number aberrations. Optimization of probe design, library generation and sequencing conditions on 150 samples resulted in a 5-workday routine workflow from the formalin-fixed paraffin embedded sample to neuropathological report. This protocol was applied to 79 retrospective cases with established molecular aberrations for validation and 71 prospective cases for discovery of potential therapeutic targets. Concordance of NGS compared to established, single biomarker methods was 98.0 %, with discrepancies resulting from one case where a TERT promoter mutation was not called by NGS and three ATRX mutations not being detected by Sanger sequencing. Importantly, in samples with low tumor cell content, NGS was able to identify mutant alleles that were not detectable by traditional methods. Information derived from NGS data identified potential targets for experimental therapy in 37/47 (79 %) glioblastomas, 9/10 (90 %) pilocytic astrocytomas, and 5/14 (36 %) medulloblastomas in the prospective target discovery cohort. In conclusion, we present the settings for high-throughput, adaptive next-generation sequencing in routine neuropathology diagnostics. Such an approach will likely become highly valuable in the near future for treatment decision making, as more therapeutic targets emerge and genetic information enters the classification of brain tumors. PMID- 26671410 TI - Astrocytes: a central element in neurological diseases. AB - The neurone-centred view of the past disregarded or downplayed the role of astroglia as a primary component in the pathogenesis of neurological diseases. As this concept is changing, so is also the perceived role of astrocytes in the healthy and diseased brain and spinal cord. We have started to unravel the different signalling mechanisms that trigger specific molecular, morphological and functional changes in reactive astrocytes that are critical for repairing tissue and maintaining function in CNS pathologies, such as neurotrauma, stroke, or neurodegenerative diseases. An increasing body of evidence shows that the effects of astrogliosis on the neural tissue and its functions are not uniform or stereotypic, but vary in a context-specific manner from astrogliosis being an adaptive beneficial response under some circumstances to a maladaptive and deleterious process in another context. There is a growing support for the concept of astrocytopathies in which the disruption of normal astrocyte functions, astrodegeneration or dysfunctional/maladaptive astrogliosis are the primary cause or the main factor in neurological dysfunction and disease. This review describes the multiple roles of astrocytes in the healthy CNS, discusses the diversity of astroglial responses in neurological disorders and argues that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer's disease as well as other neurodegenerative diseases. PMID- 26671412 TI - Chromatographic Determination of Aminoacridine Hydrochloride, Lidocaine Hydrochloride and Lidocaine Toxic Impurity in Oral Gel. AB - Two sensitive and selective analytical methods were developed for simultaneous determination of aminoacridine hydrochloride and lidocaine hydrochloride in bulk powder and pharmaceutical formulation. Method A was based on HPLC separation of the cited drugs with determination of the toxic lidocaine-related impurity 2,6 dimethylaniline. The separation was achieved using reversed-phase column C18, 250 * 4.6 mm, 5 um particle size and mobile phase consisting of 0.05 M disodium hydrogen phosphate dihydrate (pH 6.0 +/- 0.2 adjusted with phosphoric acid) and acetonitrile (55 : 45, v/v). Quantitation was achieved with UV detection at 240 nm. Linear calibration curve was in the range of 1.00-10.00, 13.20-132.00 and 1.32-13.20 ug mL(-1) for aminoacridine hydrochloride, lidocaine hydrochloride and 2,6-dimethylaniline, respectively. Method B was based on TLC separation of the cited drugs followed by densitometric measurement at 365 nm on the fluorescent mode for aminoacridine hydrochloride and 220 nm on the absorption mode for lidocaine hydrochloride. The separation was carried out using ethyl acetate methanol-acetic acid (65 : 30 : 5 by volume) as a developing system. The calibration curve was in the range of 25.00-250.00 ng spot(-1) and 0.99-9.90 ug spot(-1) for aminoacridine hydrochloride and lidocaine hydrochloride, respectively. The results obtained were statistically analyzed and compared with those obtained by applying the manufacturer's method. PMID- 26671413 TI - Transformation of the yeast Trichosporonoides oedocephalis. AB - The osmotolerant yeast, Trichosporonoides oedocephalis, is an excellent producer of erythritol, which has wide industrial applications. In this study, we developed an efficient transformation method for T. oedocephalis. To evaluate the T. oedocephalis transformation, we constructed a DNA fragment (loxP-Kan-loxP/Cre system) that was targeted to the mitogen-activated protein kinase HOG1 gene. Transformants were selected on plates containing G418 and response surface methodology was employed to obtain optimum transformation conditions. Optimal transformation could be achieved at an incubation time of 40 min, when the concentration of zymolyase-100T was 30 ug/mL, and when 100 mM CaCl2 was added to the mixture. The predicted optimal transformation efficiency was 133 transformants per ug of DNA. This novel method will facilitate studies in synthetic biology and metabolic engineering of T. oedocephalis. PMID- 26671411 TI - A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. AB - The switch between stem/progenitor cell expansion and differentiation is critical for organ homeostasis. The mammalian Hippo pathway effector and oncoprotein YAP expands undifferentiated stem/progenitor cells in various tissues. However, the YAP-associated transcription factors and downstream targets underlying this stemness-promoting activity are poorly understood. Here we show that the SRF-IL6 axis is the critical mediator of YAP-induced stemness in mammary epithelial cells and breast cancer. Specifically, serum response factor (SRF)-mediated binding and recruitment of YAP to mammary stem cell (MaSC) signature-gene promoters induce numerous MaSC signature genes, among which the target interleukin (IL)-6 is critical for YAP-induced stemness. High SRF-YAP/TAZ expression is correlated with IL6-enriched MaSC/basal-like breast cancer (BLBC). Finally, we show that this high SRF expression enables YAP to more efficiently induce IL6 and stemness in BLBC compared with luminal-type breast cancer. Collectively, our results establish the importance of SRF-YAP-IL6 signalling in promoting MaSC-like properties in a BLBC-specific manner. PMID- 26671414 TI - Multilocus phylogeny reveals an association of agriculturally important Fusarium solani species complex (FSSC) 11, and clinically important FSSC 5 and FSSC 3 + 4 with soybean roots in the north central United States. AB - The Fusarium solani species complex (FSSC) includes important root pathogens of soybean in the United States, but the evolutionary lineages associated with soybean root rot are unknown. A multilocus phylogeny based on 93 isolates from soybean and pea roots from North Dakota and Minnesota revealed that root rot was associated with three known phylogenetic species, FSSC 3 + 4 (=Fusarium falciforme) (3 % of isolates), FSSC 5 (60 %), FSSC 11 (34 %), and one unknown species, FSSC X (2 %). Of these species FSSC 5 and FSSC 3 + 4 are clinically important while FSSC 11 is a plant pathogen. Isolates from FSSC 11 were pathogenic on soybean, dry bean, pea and lentil, and did not grow at 37 degrees C. However, isolates from FSSC 5 were weakly to non-pathogenic, but grew at 37 degrees C. Isolates from both FSSC 5 and FSSC 11 were highly resistant to fludioxonil in vitro. This is the first study revealing the pathogenic robustness of FSSC 11 in causing root rot among Fabaceae crops and also the association of clinically important members of the FSSC with roots of a widely grown field crop in the United States. PMID- 26671415 TI - Microvirga makkahensis sp. nov., and Microvirga arabica sp. nov., isolated from sandy arid soil. AB - The taxonomic positions of two Gram-negative strains, SV1470(T) and SV2184P(T), isolated from arid soil samples, were determined using a polyphasic approach. Analysis of the 16S rRNA gene and the concatenated sequences of three housekeeping gene loci (dnaK, rpoB and gyrB) confirmed that the strains belong to the genus Microvirga. Strain SV1470(T) was found to be closely related to Microvirga vignae BR3299(T) (98.8 %), Microvirga flocculans TFB(T) (98.3 %) and Microvirga lupini Lut6(T) (98.2 %), whilst similarity to other type strains of the genus ranged from 97.8 to 96.3 %; strain SV2184P(T) was found to be closely related to Microvirga aerilata 5420S-16(T) (98.0 %), Microvirga zambiensis WSM3693(T) (97.8 %) and M. flocculans ATCC BAA-817(T) (97.4 %), whilst similarity to other type strains of the genus ranged from 97.2 to 95.9 %. The G + C content of the genomic DNA was determined to be 61.5 mol % for strain SV1470(T) and 62.1 mol % for strain SV2184P(T). Both strains were found to have the same quinone system, with Q-10 as the major ubiquinone. The polar lipid profile of strain SV1470(T) was found to consist of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and one unidentified aminolipid, while that of strain SV2184P(T) consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, one unidentified aminolipid, one unidentified aminophospholipid and two unidentified phospholipids. DNA-DNA relatedness studies showed that the two strains belong to different genomic species. The strains were also distinguished using a combination of phenotypic properties. Based on the genotypic and phenotypic data, the novel species Microvirga makkahensis sp. nov. (type strain SV1470(T) = DSM 25394(T) = KCTC 23863(T) = NRRL-B 24875(T)) and Microvirga arabica sp. nov. (type strain SV2184P(T) = DSM 25393(T) = KCTC 23864(T) = NRRL-B 24874(T)) are proposed. PMID- 26671416 TI - Semisynthetic and Biomolecular Hydrogen Evolution Catalysts. AB - There has been great interest in the development of stable, inexpensive, efficient catalysts capable of reducing aqueous protons to hydrogen (H2), an alternative to fossil fuels. While synthetic H2 evolution catalysts have been in development for decades, recently there has been great progress in engineering biomolecular catalysts and assemblies of synthetic catalysts and biomolecules. In this Forum Article, progress in engineering proteins to catalyze H2 evolution from water is discussed. The artificial enzymes described include assemblies of synthetic catalysts and photosynthetic proteins, proteins with cofactors replaced with synthetic catalysts, and derivatives of electron-transfer proteins. In addition, a new catalyst consisting of a thermophilic cobalt-substituted cytochrome c is reported. As an electrocatalyst, the cobalt cytochrome shows nearly quantitative Faradaic efficiency and excellent longevity with a turnover number of >270000. PMID- 26671417 TI - Sudden death during struggle in the setting of heterozygosity for a mutation in calsequesterin 2. AB - Instances of sudden and unexpected death while in police custody remain complex and controversial cases in forensic pathology, and provide unique diagnostic challenges. In general, the circumstances of these cases have resulted in two major theories to account for these deaths: "excited delirium syndrome", and positional (restraint) asphyxia. However, some cases that are not easily explained by one of these theories may be best explained by a theory from another emergent area in forensic pathology, non-structural genetic heart disease. We present one such case, a sudden arrhythmic death during struggle/restraint. A 45 year old man with developmental delay was walking outdoors as part of his daily routine. He was misidentified as a criminal suspect by police officers, who attempted to take him into custody. He resisted this arrest violently. He was taken to the ground, and restrained in a face-down position. Both police and civilian witness state that he was pushing his chest off the ground with his arms, when he suddenly collapsed and died. The interaction with police lasted approximately 3 min. There was no prior excited delirium. At autopsy, minor external blunt force injuries were observed. The heart showed mild cardiomegaly with concentric left ventricular hypertrophy, and sub-occlusive coronary atherosclerosis. Toxicological testing was negative for common drugs, including cocaine and its metabolites. Post-mortem molecular testing demonstrated this man to be heterozygous for a catecholaminergic polymorphic ventricular tachycardia (CPVT) associated mutation (Phe189Leu) in the calsequestrin 2 (CASQ2) gene. This mutation was classified as a class I mutation (deleterious), that may cause disease in a heterozygous state. The cause of death was given as cardiac arrhythmia precipitated by struggle/restraint in a man with CPVT. This case illustrates the difficulty assigning a scientific cause of death in rare and controversial cases, and the value of the molecular autopsy in identifying disease causing mutations. PMID- 26671418 TI - Incentives for increasing prenatal care use by women in order to improve maternal and neonatal outcomes. AB - BACKGROUND: Prenatal care is recommended during pregnancy as a method to improve neonatal and maternal outcomes. Improving the use of prenatal care is important, particularly for women at moderate to high risk of adverse outcomes. Incentives are sometimes utilized to encourage women to attend prenatal care visits. OBJECTIVES: To determine whether incentives are an effective tool to increase utilization of timely prenatal care among women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015) and the reference lists of all retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-RCTs, and cluster-RCTs that utilized direct incentives to pregnant women explicitly linked to initiation and frequency of prenatal care were included. Incentives could include cash, vouchers, coupons or products not generally offered to women as a standard of prenatal care. Comparisons were to no incentives and to incentives not linked directly to utilization of care. We also planned to compare different types of interventions, i.e. monetary versus products or services. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and methodological quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We identified 11 studies (19 reports), six of which we excluded. Five studies, involving 11,935 pregnancies were included, but only 1893 pregnancies contributed data regarding our specified outcomes. Incentives in the studies included cash, gift card, baby carrier, baby blanket or taxicab voucher and were compared with no incentives. Meta-analysis was performed for only one outcome 'Return for postpartum care' and this outcome was not pre-specified in our protocol. Other analyses were restricted to data from single studies.Trials were at a moderate risk of bias overall. Randomization and allocation were adequate and risk of selection bias was low in three studies and unclear in two studies. None of the studies were blinded to the participants. Blinding of outcome assessors was adequate in one study, but was limited or not described in the remaining four studies. Risk of attrition was deemed to be low in all studies that contributed data to the review. Two of the studies reported or analyzed data in a manner that was not consistent with the predetermined protocol and thus were deemed to be at high risk. The other three studies were low risk for reporting bias. The largest two of the five studies comprising the majority of participants took place in rural, low-income, homogenously Hispanic communities in Central America. This setting introduces a number of confounding factors that may affect generalizability of these findings to ethnically and economically diverse urban communities in developed countries.The five included studies of incentive programs did not report any of this review's primary outcomes: preterm birth, small-for-gestational age, or perinatal death.In terms of this review's secondary outcomes, pregnant women receiving incentives were no more likely to initiate prenatal care (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.78 to 1.38, one study, 104 pregnancies). Pregnant women receiving incentives were more likely to attend prenatal visits on a frequent basis (RR 1.18, 95% CI 1.01 to 1.38, one study, 606 pregnancies) and obtain adequate prenatal care defined by number of "procedures" such as testing blood sugar or blood pressure, vaccinations and counseling about breastfeeding and birth control (mean difference (MD) 5.84, 95% CI 1.88 to 9.80, one study, 892 pregnancies). In contrast, women who received incentives were more likely to deliver by cesarean section (RR 1.97, 95% CI 1.18 to 3.30, one study, 979 pregnancies) compared to those women who did not receive incentives.Women who received incentives were no more likely to return for postpartum care based on results of meta-analysis (average RR 0.75, 95% CI 0.21 to 2.64, two studies, 833 pregnancies, Tau2 = 0.81, I2 = 98%). However, there was substantial heterogeneity in this analysis so a subgroup analysis was performed and this identified a clear difference between subgroups based on the type of incentive being offered. In one study, women receiving non-cash incentives were more likely to return for postpartum care (RR 1.26, 95% CI 1.09 to 1.47, 240 pregnancies) than women who did not receive non-cash incentives. In another study, women receiving cash incentives were less likely to return for postpartum care (RR 0.43, 95% CI 0.30 to 0.62, 593 pregnancies) than women who did not receive cash incentives.No data were identified for the following secondary outcomes: frequency of prenatal care; pre-eclampsia; satisfaction with birth experience; maternal mortality; low birthweight (less than 2500 g); infant macrosomia (birthweight greater than 4000 g); or five-minute Apgar less than seven. AUTHORS' CONCLUSIONS: The included studies did not report on this review's main outcomes: preterm birth, small-for-gestational age, or perinatal death. There is limited evidence that incentives may increase utilization and quality of prenatal care, but may also increase cesarean rate. Overall, there is insufficient evidence to fully evaluate the impact of incentives on prenatal care initiation. There are conflicting data as to the impact of incentives on return for postpartum care. Two of the five studies which accounted for the majority of women in this review were conducted in rural, low-income, overwhelmingly Hispanic communities in Central America, thus limiting the external validity of these results.There is a need for high-quality RCTs to determine whether incentive program increase prenatal care use and improve maternal and neonatal outcomes. Incentive programs, in particular cash-based programs, as suggested in this review and in several observational studies may improve the frequency and ensure adequate quality of prenatal care. No peer-reviewed data have been made publicly available for one of the largest incentive-based prenatal programs - the statewide Medicaid-based programs within the United States. These observational data represent an important starting point for future research with significant implications for policy development and allocation of healthcare resources. The disparate findings related to attending postpartum care should also be further explored as the findings were limited by the number of studies. Future large RCTs are needed to focus on the outcomes of preterm birth, small-for-gestational age and perinatal outcomes. PMID- 26671419 TI - Tunable and Specific Formation of C@NiCoP Peapods with Enhanced HER Activity and Lithium Storage Performance. AB - The superior properties of nanomaterials with a special structure can provide prospects for highly efficient water splitting and lithium storage. Herein, we fabricated a series of peapodlike C@Ni2-x Cox P (x<=1) nanocomposites by an anion exchange pathway. The experimental results indicated that the HER activity of C@Ni2-x Cox P catalyst is strongly related to the Co/Ni ratio, and the C@NiCoP got the highest HER activity with low onset potential of ~45 mV, small Tafel slope of ~43 mV dec(-1) , large exchange current density of 0.21 mA cm(-2) , and high long-term durability (60 h) in 0.5 m H2 SO4 solutions. Equally importantly, as an anode electrode for lithium batteries, this peapodlike C@NiCoP nanocomposite gives excellent charge-discharge properties (e.g., specific capacity of 670 mAh g(-1) at 0.2 A g(-1) after 350 cycles, and a reversible capacity of 405 mAh g(-1) at a high current rate of 10 A g(-1) ). The outstanding performance of C@NiCoP in HER and LIBs could be attributed to the synergistic effect of the rational design of peapodlike nanostructures and the introduction of Co element. PMID- 26671421 TI - The ectomycorrhizal status of a tropical black bolete, Phlebopus portentosus, assessed using mycorrhizal synthesis and isotopic analysis. AB - Phlebopus portentosus is one of the most popular wild edible mushrooms in Thailand and can produce sporocarps in the culture without a host plant. However, it is still unclear whether Phlebopus portentosus is a saprotrophic, parasitic, or ectomycorrhizal (ECM) fungus. In this study, Phlebopus portentosus sporocarps were collected from northern Thailand and identified based on morphological and molecular characteristics. We combined mycorrhizal synthesis and stable isotopic analysis to investigate the trophic status of this fungus. In a greenhouse experiment, ECM-like structures were observed in Pinus kesiya at 1 year after inoculation with fungal mycelium, and the association of Phlebopus portentosus and other plant species showed superficial growth over the root surface. Fungus colonized root tips were described morphologically and colonization confirmed by molecular methods. In stable isotope measurements, the delta(13)C and delta(15)N of natural samples of Phlebopus portentosus differed from saprotrophic fungi. Based on the isotopic patterns of Phlebopus portentosus and its ability to form ECM-like structures in greenhouse experiments, we conclude that Phlebopus portentosus could be an ECM fungus. PMID- 26671422 TI - Synthesis of P-Chiral Dihydrobenzooxaphospholes Through Negishi Cross-Coupling. AB - An efficient Negishi cross-coupling was developed for the synthesis of the biaryl axes present in useful P-chiral dihydrobenzooxaphosphole ligands. This approach has allowed for the synthesis of new derivatives of these ligands that were not accessible by the previous route employing Suzuki-Miyaura cross-coupling. The use of Pd2(dba)3/BI-DIME as the catalyst system affords the desired biaryl compounds in good yields with excellent rates and with catalyst loadings as low as 0.25 mol %. PMID- 26671424 TI - Ethnic differences in cognitive development in the first 7 years: does maternal generational status matter? AB - BACKGROUND: Differences in cognitive development have been observed across a variety of ethnic minority groups but relatively little is known about the persistence of these developmental inequalities over time or generations. METHODS: A repeat cross-sectional analysis assessed cognitive ability scores of children aged 3, 5 and 7 years from the longitudinal UK Millennium Cohort Study (white UK born n=7630; Indian n=248; Pakistani n=328; Bangladeshi n=87; black Caribbean n=172; and black African n=136). Linear regression estimated ethnic differences in age normed scores at each time point. Multivariable logistic regression estimated within-group generational differences in test scores at each age adjusting stepwise for sociodemographic factors, maternal health behaviours, indicators of the home learning environment and parenting styles. RESULTS: The majority of ethnic minority groups scored lower than the white UK born reference group at 3 years with these differences narrowing incrementally at ages 5 and 7 years. However, the black Caribbean group scored significantly lower than the white UK born reference group throughout early childhood. At 3 years, Pakistani, black Caribbean and black African children with UK born mothers had significantly higher test scores than those with foreign born mothers after baseline adjustment for maternal age and child gender. Controlling for social, behavioural and parenting factors attenuated this generational advantage. By 7 years there were no significant generational differences in baseline models. CONCLUSIONS: Ethnic differences in cognitive development diminish throughout childhood for the majority of groups. Cumulative exposure to the UK environment may be associated with higher cognitive development scores. PMID- 26671425 TI - Prevalence of various comorbidities among veterans with chronic kidney disease and its comparison with other datasets. AB - Chronic kidney disease (CKD) has a complicated interrelationship with various comorbidities. The purpose of this study was to describe the prevalence of various comorbidities among veterans with CKD and compare it with other datasets like Kidney Early Evaluation Program (KEEP), National Health and Nutrition Examination Survey (NHANES) and Medicare. Patients who had at least one outpatient visit in year 2007 (1 January 2007 to 31 December 2007) were included in the study (n = 75,787). Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. CKD prevalence was calculated based on one or two serum creatinine values at least 3 months apart. Demographic data were obtained including age, gender, race, weight, height and body mass index (BMI). The prevalence of various comorbidities was also collected based on ICD 9 codes from the problem list. The prevalence of CKD among veterans was 47.3%, much higher than estimated in the US population. Patients with CKD were more likely to have any vascular disease (36.89% vs. 14.87%), diabetes (34.18% vs. 17.83%), hypertension (86.65% vs. 57.56%), and cancer (18.69% vs. 9.23%). Irrespective of age, the prevalence of vascular disease was much higher among veterans with CKD. The prevalence of coronary artery disease, peripheral vascular disease, and cancer was much higher among elderly veterans with CKD as compared to other datasets. CKD is a growing endemic associated with a high frequency of concomitant chronic illnesses. Public health resources should be applied for early recognition and risk modification of CKD. PMID- 26671426 TI - Safety and Therapeutic Potential of M2 Macrophages in Stroke Treatment. AB - Our objective was to evaluate the safety and clinical efficacy of autologous M2 macrophage transplantation in nonacute stroke patients. We also evaluated whether the intrathecal administration of macrophages influences the production of cytokines by peripheral blood cells and whether the levels of cytokines correlate with stroke severity and responsiveness to cell therapy. In this study, 13 patients (12 males and 1 female with a median age of 63 years) diagnosed with ischemic (n = 10) or hemorrhagic (n = 3) stroke were subjected to cell transplantation therapy (study group). On average, 21.9 * 10(6) autologous M2 macrophages were injected intrathecally. Thirteen matched case-control stroke patients who did not receive cell therapy comprised the control group. We did not observe any serious adverse events (i.e., intrahospital mortality, neurological worsening, and seizures) related to the cell injection. One patient in the study group and two patients in the control group died during the 6-month follow-up period due to recurrent stroke. In the study group, the NIHSS score decreased from 11 to 6 (p = 0.007) in 6 months after the therapy, whereas the patients in the control group showed a less pronounced neurological improvement (the NIHSS score decreased from 11 to 8, p = 0.07). The obvious positive response (the improvement of the NIHSS score >=3) in the study group was observed in 75% versus 18% in the control group (pFET = 0.03). M2 cell introduction did not significantly affect the production of various cytokines. Nevertheless, pretreated levels of IL-8, IL-10, and IL-4 correlated with stroke severity. Moreover, responder patients had lower spontaneous production of IL-10, FGF-beta, PDGF, VEGF, and higher stimulation indexes of IL-1beta, TNF-alpha, IFN-gamma, and IL-6 than nonresponders. These findings suggest that the intrathecal administration of autologous M2 cells in stroke patients is safe and leads to a better neurological recovery, which could be mediated through the immunomodulatory activity of M2 macrophages. PMID- 26671428 TI - [Intraosseous sampling can be valuable in emergency situations]. AB - Intraosseous administration of fluids and drugs is valuable when vascular access is difficult to achieve. Intraosseous needles are useful tools in such cases. Sampling of aspirates through such needles have raised concern regarding the possibility that aspirated bone marrow particles could damage analysis equipment. We recommend that point-of-care equipment should be used as far as possible when intraosseous aspirates are analyzed. This is especially relevant when whole blood (i.e. blood gases) is analyzed.When centrifuged, possibly occurring bone marrow particles are deposited in the pellet, whereas the supernatant essentially corresponds to plasma. We have successfully analyzed creatinine, morphine and troponin in such samples. Leucocytes and platelets, which are formed in the bone marrow, may cause falsely elevated values when intraosseous aspirates are analyzed. The risk of hemolysis, and its potential effect on certain analyses, should be considered. PMID- 26671427 TI - Variation in Herbage Biochemical Composition among Pitch Trefoil (Bituminaria bituminosa) Populations from Elba Island, Italy. AB - This study assessed the variation in herbage protein and fiber content as well as concentration of furocoumarins, plicatin B, (E)-werneria chromene, and pterocarpans of pitch trefoil (Bituminaria bituminosa) germplasm sampled in situ in both summer and autumn in Elba Island, Italy. Populations were sampled from a range of climatic and edaphic conditions, on light soils with pH > 7.5. Valuable variation occurred for forage quality and chemical composition. The quality features, relevant for a possible forage utilization of the species, were promising for the leaves, which represented about two-thirds of the total aerial biomass in early summer and the whole green regrowth in autumn. The species can also represent a source of psoralen, angelicin, plicatin B, bitucarpin A, and erybraedin C for possible pharmaceutical and/or agrochemical use, with individual populations showing high levels of these compounds. PMID- 26671423 TI - Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. AB - Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux. PMID- 26671429 TI - [Prurigo nodularis--pregabalin can be considered for more severe symptoms]. AB - Prurigo nodularis is a pruritic condition characterized by skin noduli. Different treatment options have been used with limited success. Pregabalin is a drug licensed for treatment of neuropathic pain in adults. As prurigo nodularis involves suffering for the patients and is difficult to treat, the aim of this case report is to report the effect of pregabalin treatment in seven patients with prurigo nodularis, treated in the dermatology clinic in Malmo, Sweden. Four patients experienced good effect of pregabalin, though two patients had a transient effect. Side effects of pregabalin have been reported. This case report indicates that pregabalin is a treatment option for therapy-resistant prurigo nodularis; even though one must be aware of that the effect may not be permanent and that there are side effects. The aim must be to use the drug for a limited time, taking the patient to a remission state, where the vicious itch-scratch cycle can be inhibited. PMID- 26671430 TI - [Investigation of hypokalemia]. AB - Most causes of hypokalemia could be studied relatively easily by thorough medical history and basal sampling. Moreover, difficult cases of hypokalemia should be studied systematically to identify the underlying cause so that successful long term treatments can be applied. PMID- 26671408 TI - Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage. AB - BACKGROUND: This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. RESULTS: Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). CONCLUSIONS: The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. PMID- 26671431 TI - [The Swedish stroke register indicates differences in stroke care. Unconscious discrimination might explain some of the differences]. AB - In this article, results from a series of studies on the relationships between socioeconomic factors and stroke processes (stroke unit care, acute reperfusion treatment, secondary prevention with oral anticoagulants and statins) and outcomes (long-term survival, return to work and risk of suicide and suicide attempts) are summarized. The overall pattern is that acute and secondary prevention interventions and prognosis are better in patients with a high compared with a low level of education, better in people with high than low income, better in people who are cohabitant than single. As to country of birth, a more complex pattern has emerged. Unmeasured confounding may possibly explain part of the difference, but the socioeconomic gradients remain after adjustment for multiple potential confounders, leaving the possibility that there is an element of unconscious discrimination in stroke care. PMID- 26671432 TI - ["Shermer's neck" is a rare injury in long-distance cycle races. Association with diplopia described for the first time]. AB - Shermer's neck was first described in 1983 in an ultra-distance cyclist and it is often associated with neck pain (in our patient diplopia as first symptom) and exhaustion and impaired neck motor function with inability to extend the neck against gravity. The diplopia, for the first time described in connection with Shermer's neck, was accentuated when elevating the eyes and looking at distance, most likely reflecting exhaustion in the elevator muscles of the eye. Shermer's neck usually appears after 800 km of non-stop bike racing. Risk factors include former neck injuries, staying low in aerobars for a long time, and wearing helmet light/cameras. Prevention includes neck strength training, muscle stretching, raising of handle bars and different kinds of chin support. The most important treatment is rest and not riding a bike. In our patient the diplopia was normalized after 4 hours of sleep. It can take 2-14 days to regain full neck motor function. The possibility of developing Shermer's neck and diplopia ("Berglund's diplopia") must be taken into account when many untrained individuals participate in popular shorter races over about 300 km. PMID- 26671433 TI - [Handling of misconduct in Swedish research must be improved. More strict investigative procedures, tougher punishments and withdrawals are required]. AB - Scientific misconduct constitutes a severe threat to research. Procedures to handle misconduct must therefore be both efficient and precise. In Sweden, suspected cases of misconduct are handled by the universities themselves. Investigations are generally performed by appointed scientists, leading to unnecessary discussions of the validity of the conclusions made. Sweden has a Central Ethical Review Board but this is infrequently used by the universities. It is an absolute requirement for a university to withdraw incorrect publications from the literature but regulations in this area are lacking in Sweden. The extraordinarily strong legal status of graduate students at Swedish universities leads to slow and costly investigations. Even when found to be guilty of misconduct, students are allowed to defend their PhD theses. In conclusion, there is a large potential for improvement of the regulations and routines for handling scientific misconduct in Sweden. PMID- 26671434 TI - [Do health professionals keep their new year's resolutions?]. PMID- 26671435 TI - [Continued focus on child palliation]. PMID- 26671437 TI - [Not Available]. PMID- 26671436 TI - [Skane leads the way with care program for severe sepsis]. PMID- 26671438 TI - [Not Available]. PMID- 26671439 TI - [Swedish Match: Incorrect about snuff]. PMID- 26671440 TI - [Experts: Good evidence for screening recommendations]. PMID- 26671441 TI - [Coordinated surgery--winning ticket for the patients]. PMID- 26671442 TI - [Not Available]. PMID- 26671443 TI - BMDExpress Data Viewer - a visualization tool to analyze BMDExpress datasets. AB - Regulatory agencies increasingly apply benchmark dose (BMD) modeling to determine points of departure for risk assessment. BMDExpress applies BMD modeling to transcriptomic datasets to identify transcriptional BMDs. However, graphing and analytical capabilities within BMDExpress are limited, and the analysis of output files is challenging. We developed a web-based application, BMDExpress Data Viewer (http://apps.sciome.com:8082/BMDX_Viewer/), for visualizing and graphing BMDExpress output files. The application consists of "Summary Visualization" and "Dataset Exploratory" tools. Through analysis of transcriptomic datasets of the toxicants furan and 4,4'-methylenebis(N,N-dimethyl)benzenamine, we demonstrate that the "Summary Visualization Tools" can be used to examine distributions of gene and pathway BMD values, and to derive a potential point of departure value based on summary statistics. By applying filters on enrichment P-values and minimum number of significant genes, the "Functional Enrichment Analysis" tool enables the user to select biological processes or pathways that are selectively perturbed by chemical exposure and identify the related BMD. The "Multiple Dataset Comparison" tool enables comparison of gene and pathway BMD values across multiple experiments (e.g., across timepoints or tissues). The "BMDL-BMD Range Plotter" tool facilitates the observation of BMD trends across biological processes or pathways. Through our case studies, we demonstrate that BMDExpress Data Viewer is a useful tool to visualize, explore and analyze BMDExpress output files. Visualizing the data in this manner enables rapid assessment of data quality, model fit, doses of peak activity, most sensitive pathway perturbations and other metrics that will be useful in applying toxicogenomics in risk assessment. (c) 2015 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. PMID- 26671444 TI - Insight into muscle physiology through understanding mechanisms of muscle pathology. PMID- 26671445 TI - An MLC-based version for the ecliptic method for the determination of backscatter into the beam monitor chambers in photon beams of medical accelerators. AB - A very simple method to measure the effect of the backscatter from secondary collimators into the beam monitor chambers in linear accelerators equipped with multi-leaf collimators (MLC) is presented here. The backscatter to the monitor chambers from the upper jaws of the secondary collimator was measured on three beam-matched linacs by means of three methods: this new methodology, the ecliptic method, and assessing the variation of the beam-on time per monitor unit with dose rate feedback disabled. This new methodology was used to assess the backscatter characteristics of asymmetric over-traveling jaws. Excellent agreement between the backscatter values measured using the new methodology introduced here and the ones obtained using the other two methods was established. The experimental values reported here differ by less than 1% from published data. The sensitivity of this novel technique allowed differences in backscatter due to the same opening of the jaws, when placed at different positions on the beam path, to be resolved. The introduction of the ecliptic method has made the determination of the backscatter to the monitor chambers an easy procedure. The method presented here for machines equipped with MLCs makes the determination of backscatter to the beam monitor chambers even easier, and suitable to characterize linacs equipped with over-traveling asymmetric secondary collimators. This experimental procedure could be simply implemented to fully characterize the backscatter output factor constituent when detailed dosimetric modeling of the machine's head is required. The methodology proved to be uncomplicated, accurate and suitable for clinical or experimental environments. PMID- 26671447 TI - High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo. AB - High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process. PMID- 26671449 TI - Complexity mindsets at work. PMID- 26671448 TI - Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms. AB - The objective of this study was to compare the long-term histological and behavioral outcomes after spinal cord injury (SCI) induced by one of three distinct biomechanical mechanisms: dislocation, contusion, and distraction. Thirty male Sprague-Dawley rats were randomized to incur a traumatic cervical SCI by one of these three clinically relevant mechanisms. The injured cervical spines were surgically stabilized, and motor function was assessed for the following 8 weeks. The spinal cords were then harvested for histologic analysis. Quantification of white matter sparing using Luxol fast blue staining revealed that dislocation injury caused the greatest overall loss of white matter, both laterally and along the rostrocaudal axis of the injured cord. Distraction caused enlarged extracellular spaces and structural alteration in the white matter but spared the most myelinated axons overall. Contusion caused the most severe loss of myelinated axons in the dorsal white matter. Immunohistochemistry for the neuronal marker NeuN combined with Fluoro Nissl revealed that the dislocation mechanism resulted in the greatest neuronal cell losses in both the ventral and dorsal horns. After the distraction injury mechanism, animals displayed no recovery of grip strength over time, in contrast to the animals subjected to contusion or dislocation injuries. After the dislocation injury mechanism, animals displayed no improvement in the grooming test, in contrast to the animals subjected to contusion or distraction injuries. These data indicate that different SCI mechanisms result in distinct patterns of histopathology and behavioral recovery. Understanding this heterogeneity may be important for the future development of therapeutic interventions that target specific neuropathology after SCI. PMID- 26671446 TI - Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins. AB - Dipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4 like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen presenting (DPP9), co-stimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology. PMID- 26671450 TI - Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset. AB - BACKGROUND: Early initiation of anti-retroviral treatment (ART) decreases mortality as compared to deferred treatment, but whether it preserves immune cells from early loss or promotes their recovery remains undefined. Determination of complex immunological endpoints in infants is often marred by missing data due to missed visits and/or inadequate sampling. Specialized methods are required to address missingness and facilitate data analysis. METHODS: We characterized the changes in cellular and humoral immune parameters over the first year of life in 66 HIV-infected infants (0-1 year of age) enrolled in the CHER study starting therapy within 12 weeks of birth (n = 42) or upon disease progression (n = 24). A convenience cohort of 23 uninfected infants aged 0-6 months born to mothers with HIV-1 infection was used as controls. Flow cytometry and ELISA were used to evaluate changes in natural killer (NK) cells, plasmacytoid dendritic cells (pDC), and CD4+ or CD8+ T-cell frequencies. Data missingness was assessed using Little's test. Complete datasets for analysis were created using Multiple Imputation (MI) or Bayesian modeling and multivariate analysis was conducted on the imputed datasets. RESULTS: HIV-1-infected infants had greater frequency of CD4+ T cells with naive phenotype, as well as higher serum IL-7 levels than HIV exposed/uninfected infants. The elevated data missingness was completely at random, allowing the use of both MI and Bayesian modeling. Both methods indicate that early ART initiation results in higher CD4+ T cell frequency, lower expression of CD95 in CD8+ T cell, and preservation of naive T cell subsets. In contrast, innate immune effectors appeared to be similar independently of the timing of ART initiation. CONCLUSIONS: Early ART initiation in infants with perinatal HIV infection reduces immune activation and preserves an early expansion of naive T-cells with undiminished innate cell numbers, giving greater immune reconstitution than achieved with deferred ART. Both statistical approaches concurred in this finding. PMID- 26671451 TI - Automatic Mechanisms for Social Attention Are Culturally Penetrable. AB - Are mechanisms for social attention influenced by culture? Evidence that social attention is triggered automatically by bottom-up gaze cues and is uninfluenced by top-down verbal instructions may suggest it operates in the same way everywhere. Yet considerations from evolutionary and cultural psychology suggest that specific aspects of one's cultural background may have consequence for the way mechanisms for social attention develop and operate. In more interdependent cultures, the scope of social attention may be broader, focusing on more individuals and relations between those individuals. We administered a multi-gaze cueing task requiring participants to fixate a foreground face flanked by background faces and measured shifts in attention using eye tracking. For European Americans, gaze cueing did not depend on the direction of background gaze cues, suggesting foreground gaze alone drives automatic attention shifting; for East Asians, cueing patterns differed depending on whether the foreground cue matched or mismatched background cues, suggesting foreground and background gaze information were integrated. These results demonstrate that cultural background influences the social attention system by shifting it into a narrow or broad mode of operation and, importantly, provides evidence challenging the assumption that mechanisms underlying automatic social attention are necessarily rigid and impenetrable to culture. PMID- 26671452 TI - Rhubarb Enema Attenuates Renal Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Alleviating Indoxyl Sulfate Overload. AB - AIM: To investigate the effects of rhubarb enema treatment using a 5/6 nephrectomized rat model and study its mechanisms. METHODS: Twenty-eight Sprague Dawley rats were divided into three groups: sham operation group (n = 8), 5/6 nephrectomized (5/6Nx) (n = 10), and 5/6Nx with rhubarb enema treatment (n = 10). The rhubarb enema was continuous for 1.0 month. Serum creatinine, serum indoxyl sulfate (IS) level, renal pathology, tubulointerstitial fibrosis, and renal oxidative stress were assessed. RESULTS: 5/6Nx rats showed increasing levels of serum creatinine and severe pathological lesions. Their serum creatinine levels obviously decreased after rhubarb enema treatment (P < 0.05 vs 5/6Nx group). The administration of rhubarb enema attenuated the histopathological changes in 5/6Nx rats. In addition, 5/6Nx rats showed an enhanced extent of tubulointerstitial fibrosis compared with sham rats, and administration of rhubarb enema to 5/6Nx rats ameliorated tubulointerstitial fibrosis. 5/6Nx rats showed increased serum levels of IS, renal oxidative stress, and NF-kappaB compared with sham rats, whereas administration of rhubarb enema to 5/6Nx rats decreased serum levels of IS, renal oxidative stress, and NF-kappaB levels. CONCLUSION: Rhubarb enema treatment ameliorates tubulointerstitial fibrosis in the kidneys of 5/6Nx rats, most likely by alleviating IS overload and reducing kidney oxidative stress and inflammatory injury. PMID- 26671453 TI - A white spot syndrome virus microRNA promotes the virus infection by targeting the host STAT. AB - JAK/STAT pathway plays an important role in invertebrates during virus infection. However the microRNA (miRNA)-mediated regulation of JAK/STAT is not intensively investigated. Viral miRNAs, encoded by virus genome, have emerged as important regulators in the virus-host interactions. In this study, a WSSV (white spot syndrome virus)-encoded miRNA (WSSV-miR-22) was characterized in shrimp during virus infection. The results showed that the viral miRNA could promote WSSV infection in shrimp by targeting the host STAT gene. When the expression of JAK or STAT was knocked down by sequence-specific siRNA, the WSSV copies in shrimp were significantly increased, indicating that the JAK/STAT played positive roles in the antiviral immunity of shrimp. The further findings revealed that TEP1 and TEP2 were the effectors of JAK-STAT signaling pathway. The silencing of TEP1 or TEP2 led to an increase of WSSV copies in shrimp, showing TEP1 and TEP2 were involved in the shrimp immune response against virus infection. Therefore our study presented a novel viral miRNA-mediated JAK/STAT-TEP1/TEP2 signaling pathway in virus infection. PMID- 26671454 TI - A haemostatic technique using silicone gel dressing for burn surgery. AB - Significant blood loss and high rates of transfusion remain ongoing concerns in burn surgery. We have reported a haemostatic technique using silicone gel dressing to minimise bleeding during tangential excision in burn surgery. The purpose of this study was to identify the efficacy of our novel haemostatic technique for burn surgery. This study was a retrospective observational study. From 1 April 2011 to 31 March 2015, we collated data including pre- and 24-hour postoperative haemoglobin levels from patients over 15 years of age who underwent tangential excision for burn injuries. We also collected data on the amounts of measured blood loss, blood transfusions, excised areas, harvest areas and duration of surgeries. The collected data were divided into a conventional group and a silicone gel dressing group. Then, we analysed the differences between the two groups. During the study period, 357 patients were admitted to our burn centre, and 60 operations (44 patients) were performed by tangential excision. The conventional group comprised 28 operations (20 patients), and the silicone gel dressing group comprised 32 operations (26 patients). Excised areas and harvested areas were significantly larger in the silicone gel dressing group than in the conventional group. The amount of blood loss per percent excised and the number of units of blood transfused were significantly lower in the silicone gel dressing group. Duration of the surgeries was almost the same between the two groups. Application of our new technique during tangential excision for burn injuries resulted in a remarkable reduction in blood loss and transfusion requirements. PMID- 26671455 TI - The impact of natural modes in plasmonic imaging. AB - Plasmonic imaging is crucial for understanding cellular behaviours for biological sciences, where is used to image and track organelles in cells, such as DNA and virus molecules. Due to the fast dynamics of the intra-cellular processes, it is essential to keep the cells under their native states (i.e. label-free), establishing plasmonic imaging as one of the most powerful tools for studying biological samples. In this article, a theoretical model is presented that accurately predicts the properties of a plasmonic image, paving the route towards the characterization of an imaged nano-object. It is shown that natural modes are not only excited, but actually dominate the intensity and shape of the observed plasmonic image. Hence, the proposed model explains the dynamics forming the plasmonic image and can be used to extract spectroscopy information from current plasmonic imaging techniques. PMID- 26671456 TI - Three decades of eating disorders in Dutch primary care: decreasing incidence of bulimia nervosa but not of anorexia nervosa. AB - BACKGROUND: Whether the incidence of eating disorders in Western, industrialized countries has changed over time has been the subject of much debate. The purpose of this primary-care study was to examine changes in the incidence of eating disorders in The Netherlands during the 1980s, 1990s and 2000s. METHOD: A nationwide network of general practitioners (GPs), serving a representative sample (~1%) of the total Dutch population, recorded newly diagnosed patients with anorexia nervosa (AN) and bulimia nervosa (BN) in their practice during 1985 1989, 1995-1999, and 2005-2009. GPs are key players in the Dutch healthcare system, as their written referral is mandatory in order to get access to specialized (mental) healthcare, covered by health insurance. Health insurance is virtually universal in The Netherlands (99% of the population). A substantial number of GPs participated in all three study periods, during which the same case identification criteria were used and the same psychiatrist was responsible for making the final diagnoses. Incidence rates were calculated and for comparison between periods, incidence rate ratios. RESULTS: The overall incidence rate of BN decreased significantly in the past three decades (from 8.6 per 100,000 person years in 1985-1989 to 6.1 in 1995-1999, and 3.2 in 2005-2009). The overall incidence of AN remained fairly stable during three decades, i.e. 7.4 per 100,000 person-years in 1985-1989, 7.8 in 1995-1999, and 6.0 in 2005-2009. CONCLUSIONS: The incidence rate of BN decreased significantly over the past three decades, while the overall incidence rate of AN remained stable. PMID- 26671459 TI - Average duration of treatment with antidepressants among concession card holders in Australia. AB - OBJECTIVE: To analyse the average treatment duration with antidepressants that are reimbursed for concession card holders under the Pharmaceutical Benefits Scheme in Australia. METHOD: This pharmacoepidemiological study was based on a representative 10% sample of patients receiving Pharmaceutical Benefits Scheme prescriptions. Antidepressants redeemed by concession card holders in the period from 2010 to 2013 were analysed. A 5-year baseline period was used to exclude prevalent users from incident users. Estimation of treatment duration was based on the epidemiological equation: prevalence/incidence = average duration. The mean value for prevalence and incidence over the studied period was used in the equation. RESULTS: The number of prevalent and incident users increased from 90,475 to 103,305 and from 25,006 to 26,289, respectively. The epidemiological average treatment duration in the period was about 4 years. When considered by age-bands, average treatment duration was 2 years in patients under 24 years, 3 years in patients 35 to 44 years and up to 5 years in the 55 to 64 year age group. Of new users of antidepressants reimbursed under the Pharmaceutical Benefits Scheme, 86% received their first prescription from general practitioners, 4.3% from psychiatrists and 9.7% from other physicians. CONCLUSION: While recommendations have underlined the importance of giving antidepressants for a sufficient period of time, the results from this study show that it is as important to remind general practitioners to review patients on antidepressant treatment regularly, and try to cease drug treatment when timely. PMID- 26671458 TI - HIV-1 increases TLR responses in human primary astrocytes. AB - Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. They provide trophic support to neurons and are immune cells with key roles during states-of-inflammation. The potential for production of proinflammatory cytokines and its consequences has been studied in the context of HIV-1 infection of normal human astrocytes (NHA). NHA express TLR3, TLR4, and TLR5. TLR3 ligation induced the strongest proinflammatory polarizing response, characterized by generation of high levels of TNF-alpha, IL-6, and IL-8. HIV-1 increased the transient production of key inflammatory mediators, and exposure to LPS of HIV-1-infected cells increased significantly the cytokine secretion. We confirmed that it is necessary viral gene expression from the moment of pretreatment with antiretrovirals inhibited totally HIV-1-induced TLR response. The higher response to LPS from HIV-1-infected cells did not correlate with TLR4 or MyD88 increased expression. LPS responsiveness of infected cells parallels MHC class II expression, but not CD14. HIV-1-infected NHA present increased sensitivity to the proinflammatory effects of LPS. If this phenomenon occurs in vivo, it will contribute to the immunopathogenesis of this disease and may ultimately offer novel targets for immunomodulatory therapy. PMID- 26671457 TI - The Time Scale of Recombination Rate Evolution in Great Apes. AB - We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15 Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- and between-species genome wide recombination rate variation in several close relatives. PMID- 26671460 TI - Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors. AB - Opioid neuropeptides and their receptors are evolutionarily conserved neuromodulatory systems that profoundly influence behavior. In dorsal striatum, which expresses the endogenous opioid enkephalin, patches (or striosomes) are limbic-associated subcompartments enriched in mu opioid receptors. The functional implications of opioid signaling in dorsal striatum and the circuit elements in patches regulated by enkephalin are unclear. Here, we examined how patch output is modulated by enkephalin and identified the underlying circuit mechanisms. We found that patches are relatively devoid of parvalbumin-expressing interneurons and exist as self-contained inhibitory microcircuits. Enkephalin suppresses inhibition onto striatal projection neurons selectively in patches, thereby disinhibiting their firing in response to cortical input. The majority of this neuromodulation is mediated by delta, not mu-opioid, receptors, acting specifically on intra-striatal collateral axons of striatopallidal neurons. These results suggest that enkephalin gates limbic information flow in dorsal striatum, acting via a patch-specific function for delta opioid receptors. PMID- 26671461 TI - Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons. AB - We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/ ) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. PMID- 26671464 TI - Effects of Modifier Type on Properties of in Situ Organo-Montmorillonite Modified Wood Flour/Poly(lactic acid) Composites. AB - Wood flour (WF) was modified with sodium-montmorillonite (Na-MMT) and two types of surfactant modifiers, namely, didecyl dimethylammonium chloride (DDAC) and sodium dodecyl sulfonate (SDS) though a two-step process inside WF. The thus modified WFs were characterized, and the effects of MMT type on physical, mechanical, and thermal properties of their composites with poly(lactic acid) (PLA) were investigated. The results showed: (1) either DDAC or SDS could modified Na-MMT into OMMT, and then uniformly distributed in WF cell walls; (2) OMMT improved the physical properties, most mechanical properties, and thermal properties of the composites except for the impact strength; and (3) compared with SDS, DDAC seemed to perform better in properties of composites. However, DDAC showed some negative effect on the early stage of composite thermal decomposition. PMID- 26671462 TI - Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function. AB - Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID- 26671463 TI - TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. AB - Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development. PMID- 26671466 TI - Special Collection: Closing the Gaps in Skin Wound Healing. PMID- 26671465 TI - Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer. AB - BACKGROUND: Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear. METHODS: Tumor attenuation as measured by Hounsfield units (HU) in contrast enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study. RESULTS: 141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5% 20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13). CONCLUSION: Regorafenib showed prominent anti angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies. PMID- 26671469 TI - Letter to the editor: Parasympathetic innervation of the rodent spleen? PMID- 26671467 TI - Self-Administered Outpatient Antimicrobial Infusion by Uninsured Patients Discharged from a Safety-Net Hospital: A Propensity-Score-Balanced Retrospective Cohort Study. AB - BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is accepted as safe and effective for medically stable patients to complete intravenous (IV) antibiotics in an outpatient setting. Since, however, uninsured patients in the United States generally cannot afford OPAT, safety-net hospitals are often burdened with long hospitalizations purely to infuse antibiotics, occupying beds that could be used for patients requiring more intensive services. OPAT is generally delivered in one of four settings: infusion centers, nursing homes, at home with skilled nursing assistance, or at home with self-administered therapy. The first three-termed healthcare-administered OPAT (H-OPAT)--are most commonly used in the United States by patients with insurance funding. The fourth--self administered OPAT (S-OPAT)--is relatively uncommon, with the few published studies having been conducted in the United Kingdom. With multidisciplinary planning, we established an S-OPAT clinic in 2009 to shift care of selected uninsured patients safely to self-administration of their IV antibiotics at home. We undertook this study to determine whether the low-income mostly non-English speaking patients in our S-OPAT program could administer their own IV antimicrobials at home with outcomes as good as, or better than, those receiving H-OPAT. METHODS AND FINDINGS: Parkland Hospital is a safety-net hospital serving Dallas County, Texas. From 1 January 2009 to 14 October 2013, all uninsured patients meeting criteria were enrolled in S-OPAT, while insured patients were discharged to H-OPAT settings. The S-OPAT patients were trained through multilingual instruction to self-administer IV antimicrobials by gravity, tested for competency before discharge, and thereafter followed at designated intervals in the S-OPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. The primary outcome was 30-d all-cause readmission, and the secondary outcome was 1-y all-cause mortality. The study was adequately powered for readmission but not for mortality. Clinical, sociodemographic, and outcome data were collected from the Parkland Hospital electronic medical records and the US census, constituting a historical prospective cohort study. We used multivariable logistic regression to develop a propensity score predicting S-OPAT versus H-OPAT group membership from covariates. We then estimated the effect of S OPAT versus H-OPAT on the two outcomes using multivariable proportional hazards regression, controlling for selection bias and confounding with the propensity score and covariates. Of the 1,168 patients discharged to receive OPAT, 944 (81%) were managed in the S-OPAT program and 224 (19%) by H-OPAT services. In multivariable proportional hazards regression models controlling for confounding and selection bias, the 30-d readmission rate was 47% lower in the S-OPAT group (adjusted hazard ratio [aHR], 0.53; 95% CI 0.35-0.81; p = 0.003), and the 1-y mortality rate did not differ significantly between the groups (aHR, 0.86; 95% CI 0.37-2.00; p = 0.73). The S-OPAT program shifted a median 26 d of inpatient infusion per patient to the outpatient setting, avoiding 27,666 inpatient days. The main limitation of this observational study-the potential bias from the difference in healthcare funding status of the groups-was addressed by propensity score modeling. CONCLUSIONS: S-OPAT was associated with similar or better clinical outcomes than H-OPAT. S-OPAT may be an acceptable model of treatment for uninsured, medically stable patients to complete extended courses of IV antimicrobials at home. PMID- 26671470 TI - Reply to "Letter to the editor: Parasympathetic innervation of the rodent spleen?". PMID- 26671471 TI - Letter to the editor: Ketamine-only versus isoflurane effects on murine cardiac function: comparison at similar depths of anesthesia? PMID- 26671472 TI - Reply to: "Letter to the editor: Ketamine-only versus isoflurane effects on murine cardiac function: comparison at similar depths of anesthesia?". PMID- 26671473 TI - The regulatory function of microRNA-1 in arrhythmias. AB - Arrhythmia, the basis of which is cardiomyocyte ion channel abnormalities, poses a serious threat to human health. A large number of studies have demonstrated that miRNA-1(miR-1) is involved in the occurrence of arrhythmia in many myocardial pathological conditions by post-transcriptionally regulating a variety of ion channels and proteins related to cardiac electrical activity. We aim at emphasizing the relationship between miR-1 and ion channels and proteins involved in the process of arrhythmia. In addition, we will pay attention to its future therapeutic prospects. PMID- 26671474 TI - Newborn screening for congenital adrenal hyperplasia in Tokyo, Japan from 1989 to 2013: a retrospective population-based study. AB - BACKGROUND: Congenital adrenal hyperplasia (CAH) cause life-threatening adrenal crisis. It also affects fetal sex development and can result in incorrect sex assignment at birth. In 1989, a newborn screening program for congenital adrenal hyperplasia (CAH) was introduced in Tokyo. Here we present the results of this screening program in order to clarify the efficiency of CAH screening and the incidence of CAH in Japan. METHOD: From 1989 to 2013, a total of 2,105,108 infants were screened for CAH. The cutoff level for diagnosis of CAH was adjusted for gestational age and birth weight. RESULTS: A total of 410 infants were judged positive, and of these, 106 patients were diagnosed with CAH, indicating a positive predictive value (PPV) of 25.8 %. Of the 106 patients, 94 (88.7 %) were diagnosed with 21-OHD. Of these 94 patients, 73 were diagnosed with the salt wasting form, 14 with the simple virilising form and 7 with the nonclassical form (NC21OHD). The mean birth weight and gestational age were 3192 +/- 385 g and 38.9 +/- 1.38 weeks. 11 out of 44 female patients were assigned as female according to their screening result. CONCLUSIONS: These data suggest that the newborn screening in Tokyo was effective, especially for sex assignment and preventing fatal adrenal crisis. The incidence of CAH was similar to that measured in previous Japanese screening studies, and it was also similar to that of western countries. The incidence of NC21OHD in Japan in the present study was lower than that in western countries as previous studies reported. The screening program achieved higher PPV than previous CAH screening studies, which might be due to the use of variable cutoffs according to gestational age and birth weight. However, most of the neonates born at 37 weeks or less that were referred to hospital were false-positives. Further changes are needed to reduce the number of false positive preterm neonates. PMID- 26671476 TI - Flagship "seven day working" hospital doesn't provide full seven day service, doctors say. PMID- 26671475 TI - Erratum to: Outcome analysis of 215 patients with parotid gland tumors: a retrospective cohort analysis. PMID- 26671478 TI - ToF-SIMS multivariate analysis of surface-grafted small bioactive molecules. AB - In the development of bioactive coatings on biomaterials, it is essential to characterize the successful fabrication and the uniformity of intended coatings by sensitive surface analytical techniques, so as to ensure reliable interpretation of observed biointerfacial responses. This can, however, be challenging when small bioactive molecules are grafted onto biomaterials surfaces at sub- and near-monolayer densities. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides the required sensitivity, but ion signals from small grafted molecules may still be dominated by fragment ions from the underlying polymer. In such cases, multivariate analysis provides valuable enhancement of spectral data, as illustrated here by examples comprising the surface grafting of bioactive serrulatane molecules, the peptide GRGDSP, the oligonucleotide 15-thymidine, and the antifungal compound Amphotericin B. The authors also show how ToF-SIMS plus principal component analysis can distinguish between covalent grafting and physisorption of the antibiotics caspofungin and micafungin. PMID- 26671479 TI - Recent experimental advances on hydrophobic interactions at solid/water and fluid/water interfaces. AB - Hydrophobic effects play important roles in a wide range of natural phenomena and engineering processes such as coalescence of oil droplets in water, air flotation of mineral particles, and folding and assembly of proteins and biomembranes. In this work, the authors highlight recent experimental attempts to reveal the physical origin of hydrophobic effects by directly quantifying the hydrophobic interaction on both solid/water and fluid/water interfaces using state-of-art nanomechanical techniques such as surface forces apparatus and atomic force microscopy (AFM). For solid hydrophobic surfaces of different hydrophobicity, the range of hydrophobic interaction was reported to vary from ~10 to >100 nm. With various characterization techniques, the very long-ranged attraction (>100 nm) has been demonstrated to be mainly attributed to nonhydrophobic interaction mechanisms such as pre-existing nanobubbles and molecular rearrangement. By ruling out these factors, intrinsic hydrophobic interaction was measured to follow an exponential law with decay length of 1-2 nm with effective range less than 20 nm. On the other hand, hydrophobic interaction measured at fluid interfaces using AFM droplet/bubble probe technique was found to decay with a much shorter length of ~0.3 nm. This discrepancy of measured decay lengths is proposed to be attributed to inherent physical distinction between solid and fluid interfaces, which impacts the structure of interface-adjacent water molecules. Direct measurement of hydrophobic interaction on a broader range of interfaces and characterization of interfacial water molecular structure using spectroscopic techniques are anticipated to help unravel the origin of this rigidity-related mismatch of hydrophobic interaction and hold promise to uncover the physical nature of hydrophobic effects. With improved understanding of hydrophobic interaction, intrinsic interaction mechanisms of many biological and chemical pathways can be better elucidated, and novel devices/processes can be developed with capacity to modulate and control the hydrophobic effects from the molecular to the macroscopic scale. PMID- 26671477 TI - Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model. AB - BACKGROUND: The limited efficacy of current treatments against pancreatic cancer has prompted the search of new alternatives such as virotherapy. Activation of the immune response against cancer cells is emerging as one of the main mechanisms of action of oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replication within the tumor microenvironment is a potent danger signal. Arming OV with immunostimulatory transgenes further enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage of OV as cancer vaccines because repeated viral administrations may polarize immune responses against strong viral antigens, and the rapid onset of neutralizing antibodies limits the efficacy of redosing. An alternative paradigm based on sequential combination of antigenically distinct OV has been recently proposed. METHODS: We have developed a protocol consisting of sequential intratumor administrations of new Adenovirus (Ad) and Newcastle Disease Virus (NDV)-based OV encoding the immunostimulatory cytokine oncostatin M (OSM). Transgene expression, toxicity and antitumor effect were evaluated using an aggressive orthotopic pancreatic cancer model in Syrian hamsters, which are sensitive to OSM and permissive for replication of both OVs. RESULTS: NDV-OSM was more cytolytic, whereas Ad-OSM caused higher OSM expression in vivo. Both viruses achieved only a marginal antitumor effect in monotherapy. In addition, strong secretion of OSM in serum limited the maximal tolerated dose of Ad-OSM. In contrast, moderate doses of Ad-OSM followed one week later by NDV-OSM were safe, showed a significant antitumor effect and stimulated immune responses against cancer cells. Similar efficacy was observed when the order of virus administrations was reversed. CONCLUSION: Sequential administration of oncolytic Ad and NDV encoding OSM is a promising approach against pancreatic cancer. PMID- 26671480 TI - ToF-SIMS and laser-SNMS analysis of Madin-Darby canine kidney II cells with silver nanoparticles using an argon cluster ion beam. AB - The use of nanoparticles is one of the fastest expanding fields in industrial as well as in medical applications, owing to their remarkable characteristics. Silver nanoparticles (AgNPs) are among the most-commercialized nanoparticles because of their antibacterial effects. Laser postionization secondary neutral mass spectrometry (laser-SNMS) and time-of-flight secondary ion mass spectrometry in combination with argon cluster ion sputtering was used for the first time to investigate the effects of AgNPs on Madin-Darby canine kidney (MDCK) II cells. Depth profiles and high-resolution three dimensional (3D) images of nanoparticles and organic compounds from cells were obtained using an Ar cluster ion beam for sputtering and Bi3 (+) primary ions for the analysis. The 3D distribution of AgNPs and other organic compounds in MDCK II cells could be readily detected with very high efficiency, sensitivity, and submicron lateral resolution. The argon cluster ion beam is well suited for the sputtering of biological samples. It enables a high sample removal rate along with low molecular degradation. The outer membrane, the cytoplasm, and the nuclei of the cells could be clearly visualized using the signals PO(+) and C3H8N(+) or CN(+) and C3H8N(+). The laser SNMS images showed unambiguously that AgNPs are incorporated by MDCK II cells and often form silver aggregates with a diameter of a few micrometers, mainly close to the outside of the cell nuclei. PMID- 26671481 TI - Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery. AB - OBJECTIVES: This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders. METHODS: Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving >=6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider's (Recovery Markers Inventory [RMI]) and patient's (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI. RESULTS: A total of 219 patients were identified and included in the study. Results of the final three level HLMs indicated an overall increase in CRM scores (p < 0.05), an overall increase (p < 0.01), and an increased rate of change (p < 0.05) in RMI scores during the paliperidone palmitate LAI treatment period vs the pre-treatment period. LIMITATIONS: This study contained a retrospective, non-comparative design, and did not adjust for multiplicity Conclusions: The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug's use as schizophrenia treatment from a recovery-oriented perspective. PMID- 26671482 TI - Acute Leaks Following Laparoscopic Sleeve Gastrectomy: Early Surgical Repair According to a Management Algorithm. AB - INTRODUCTION: Despite leakages remaining a worrisome complication, laparoscopic sleeve gastrectomy (LSG) has become the preferred choice for most bariatric surgeons in Italy. In light of the emerging trend to discharge patients on postoperative day (POD) 1 or to consider LSG as an outpatient procedure, we felt it useful in selected cases to define a treatment protocol aimed to manage patients presenting with an acute postoperative leakage. PATIENTS AND METHODS: Starting from 2007, 295 LSGs have been performed at our institution. Six patients, including 5 from our series (1.6%), were treated for a leak. The first patient presented a leak on POD 3, whereas the next 2 patients were re-admitted on POD 11 and 12, respectively. They all underwent a conservative treatment. The last 3 patients, according to a suggested algorithm, underwent a prompt surgical repair. RESULTS: The conservatively treated patients were discharged following 22 +/- 7.7 days, whereas patients treated by surgery were discharged following 10 +/ 0.8 days (P = .09). By not considering the cost of primary LSG, which is about 5600 ? in our region, the expense for every patient treated by re-intervention was about 2500 ?. The cost for each patient treated by stenting was about 4700 ?. The cost for each patient treated conservatively was about 5700 ?. CONCLUSIONS: According to our series and in agreement with published data, it is reasonable in selected cases to consider a wider role for early surgery. A timely surgical approach following an appropriate algorithm may offer a resolutive and cost effective answer to the management of acute leaks following LSG. PMID- 26671483 TI - Uptake of manganese from manganese-lysine complex in the primary rat intestinal epithelial cells. AB - This study was conducted to compare the differences of the uptake of Mn from Mn lysine complex (MnLys) and MnSO4 and to determine the potential mechanisms of the uptake of Mn from MnLys. We first established the primary rat intestinal epithelial cell culture model and used it to determine the uptake of Mn from different Mn sources. The MnLys increased (p < 0.001) Mn uptake when compared to MnSO4 . The uptake of Mn decreased (p < 0.05) with added Fe concentration increasing in the medium regardless of Mn source. The MnLys decreased (p < 0.01) Mn2+ efflux transporter ferroportin 1 (FPN1) mRNA level, but did not influence (p > 0.06) Mn2+ influx transporter DMT1 mRNA expression when compared to MnSO4 . The results above indicated that the increase of Mn accumulation for MnLys at least partly was due to the decrease of Mn efflux by reduced FPN1 expression. The N ethylmaleimide, as an l-lysine transport system y+ inhibitor, decreased (p < 0.001) the uptake of Mn from MnLys, but did not affect (p > 0.10) the uptake of Mn from MnSO4 . The cycloheximide, as an l-lysine transport system b0,+ activator, increased (p < 0.001) the uptake of Mn from MnLys, whereas also did not influence the uptake of Mn from MnSO4 . The MnLys increased (p < 0.01) the system y+ member cationic amino acid transporter (CAT) 1, and system b0,+ components rBAT and b0,+ AT mRNA expression when compared to MnSO4 . These results suggested that the uptake of Mn from MnLys complex might be transported by CAT1 and system b0,+ , which was different from ionized Mn2+ uptake pathway. In conclusion, the uptake of MnLys complex not only might be absorbed as Mn2+ , but also appeared to be transported through CAT1 and system b0,+ in the primary rat intestinal epithelial cells. PMID- 26671484 TI - Effectiveness and potential mechanisms of intralipid in treating unexplained recurrent spontaneous abortion. AB - AIM: Abnormal natural killer (NK) cell activity has been suggested to be a high risk factor associated with unexplained recurrent spontaneous abortion (URSA). Intralipid, like immunoglobulin, is able to lower the activity of NK cells, which has been reported to be useful for improving URSA outcomes in pregnancy. This study aimed to determine whether intralipid could be used as an alternative treatment to intravenous immunoglobulin (IVIG) which is expensive and has many side-effects. METHODS: A prospective, randomized clinical trial was conducted from December 2010 to December 2012. Eligible participants were matched and sorted randomly into the intralipid and the IVIG group. The primary outcome was the rate of successful pregnancy. In addition, comparisons of peripheral NK cell activities were accessed by flow cytometry. Moreover, the effects of intralipid on trophoblasts were investigated using a Matrigel assay with the JEG-3 cell line. RESULTS: Seventy-six patients in the intralipid group and 78 in the IVIG group completed the trial. There were no statistically significant differences in successful pregnancy rates between the two groups (92.1 vs 88.2 %, P = 0.415). The reduced NK cell concentrations revealed the cytotoxic effects of the treatments in both groups. The invasive ability of JEG-3 cells was inhibited during co-culture with patient PBMCs. However, the inhibitory effect could be alleviated if the patient PBMCs were stimulated with intralipid. CONCLUSIONS: Intralipid can be used as an alternative treatment to IVIG for URSA, and its potential mechanism of action may occur by regulating NK cell function and promoting trophoblast invasion. PMID- 26671485 TI - Effectiveness of local anesthetic on postoperative pain in different levels of laparoscopic gynecological surgery. AB - PURPOSE: The aim of this study was to assess the effects of preemptive and preclosure analgesia on postoperative pain intensity in patients undergoing different levels of laparoscopic surgery. METHODS: Two hundred and twenty-six patients who underwent laparoscopic gynecological surgery were enrolled in this quasi-randomized, prospective, placebo controlled study. The operations were classified as level 1 or level 2 according to the extent of the surgery. Lidocaine 1 % was administered at the port sites before making the incision in the preincisional study group. In preincisional control group, same amount of saline was infiltrated in same manner. Lidocaine 1 % was infiltrated at the port site immediately after removing the trocars in preclosure study group. In preclosure control group, the same amount of saline was infiltrated in the same manner. Postoperative pain intensity was evaluated by linear visual analogue scale. RESULTS: It was found that preclosure lidocaine infiltration was more effective on postoperative pain intensity than its placebo group in level 1 and level 2 surgery groups at 1 and 2 h postoperatively. The administration of preincisional lidocaine improved postoperative pain scores significantly more than its placebo group in level 1 laparoscopic surgery group at 1 and 2 h postoperatively and in level 2 laparoscopic surgery group at 1 h postoperatively. CONCLUSION: Lidocaine infiltration at port sites had beneficial effects on pain intensity in the early postoperative period after laparoscopic gynecological surgery. However, the results of present study showed that the analgesic effect mechanism of local anesthetic was unrelated to the preemptive analgesia hypothesis. PMID- 26671486 TI - Final comment on the nationality of Ibni Sina. PMID- 26671487 TI - Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma. AB - PURPOSE: Type I endometrial cancer is a common tumor of the female genital tract. Since in post-menopausal women aromatase enzyme can stimulate the endometrial tissue neoplastic growth, the use of aromatase inhibitors may have a therapeutic effect, especially in patients not eligible for surgery. METHODS: A systematic review has been performed, with a very specific scope, i.e., the use of aromatase inhibitors in the treatment of advanced or recurrent endometrial cancer, as a single agent or in combination with others drugs. RESULTS: On the basis of the 117 records retrieved from the bibliographic search, the rationale for the use of aromatase inhibitors in endometrial cancer therapy is discussed. Six papers fall within the scope of our systematic review and their results are thoroughly analyzed. Moreover, we report our experience on the clinical effectiveness of anastrozole in the post-chemotherapy treatment of a patient affected by advanced stage endometrial cancer. CONCLUSION: In general, aromatase inhibitors seem to have limited clinical benefit in the treatment of advanced and recurrent endometrial cancer, although further clinical trials are necessary to investigate more in depth their role. In our case, we experienced a positive feedback in terms of control of an advanced-stage disease. PMID- 26671496 TI - Reducing head computed tomography after mild traumatic brain injury: Screening value of clinical findings and S100B protein levels. AB - PRIMARY OBJECTIVE: The present prospective study was performed to investigate whether primary clinical findings and serum S100B concentrations at 3 and 6 hours post-trauma can contribute to the selection of patients for an initial computed tomography (CT) scanning. RESEARCH DESIGN AND METHODS: S100B was measured in serum samples obtained at 3 and 6 hours after the injury. Adjusted odds ratios (OR) and 95% confidence interval (CI) associated with demographics and clinical predictors of positive CT scan were calculated. Sensitivity, specificity, negative and positive predictive values were also calculated for S100B levels. MAIN OUTCOMES AND RESULTS: It was found that the presence of loss of consciousness (OR = 2.3; 95% CI = 1.00-4.01; p = 0.008) and post-traumatic vomiting >= 2 episodes (OR = 1.8; 95% CI = 1.08-3.29; p = 0.019) are factors associated with positive CT scan. In this study the best cut-off point of 0.115 ug L(-1) for 3-hour S100B has sensitivity of 94.9% (95% CI = 86.8-98.3) with specificity of 35.4% (95% CI = 25.2-47.0) to predict intracranial injury on CT scanning. The corresponding results for 6-hour S100B > 0.210 ug L(-1) were 98.7% (95% CI = 92.1-99.9) for sensitivity and 39.2% (95% CI = 28.6-50.8) for specificity. CONCLUSIONS: Serum S100B measurement along with clinical evaluation of patients with mild traumatic brain injury has promising screening value to support selection of patients for CT scanning. PMID- 26671497 TI - First microbiota assessments of children's paddling pool waters evaluated using 16S rRNA gene-based metagenome analysis. AB - Insufficient chloric sterilization of children's paddling pool waters increases the risk of diarrheal illness. Therefore, we investigated the microbiota changes after children use pools. First, we applied 16S rRNA gene-based metagenome analysis to understand the dynamics of microbiota in pool water, especially with respect to the bio-contamination by potential pathogens. Proteobacteria were major taxa detected in every pool water sample after children spent time in the pool. In more detail, Gammaproteobacteria comprised the dominant class, which was followed by Betaproteobacteria. Five phyla, Bacteroidetes, Firmicutes, Actinobacteria and Deinococcus-Thermus phyla were minor groups. The pool water microbiota are likely to be a consortium of intestinal and skin microbiota from humans. Interestingly, the ratio of Gammaproteobacteria and Betaproteobacteria differed according to the age of the children who used the pool, which means the pool water was additionally contaminated by soil microbiota as a result of the children's behavior. Furthermore, potential pathogens, such as Campylobacter spp., Comamonas testosteroni and Burkholderia pseudomallei, were also found. Considering the standard plate counts, the abundances of these human pathogens are unlikely to be a sufficiently infectious dose. We suggest the importance of sanitary measures in paddling pool waters to reduce bio-contamination from both humans and the environment. PMID- 26671504 TI - Exceptions in patterns of arsenic compounds in urine of acute promyelocytic leukaemia patients treated with As2O3. AB - Arsenic trioxide (As(III) in solution) has been shown to be the most active single agent in combating acute promyelocytic leukemia (APL). It is metabolized and excreted via urine as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V), along with excess As(III). In our study eight APL patients were treated (intravenously) with 0.15 mg As2O3/kg/day. During the therapy As(III) and its metabolites were followed in pre- and post-infusion urine using HPLC for separation followed by on-line detection using hydride generation-atomic fluorescence spectrometry. Five patients had a normal excretion pattern of residual arsenic compounds in morning pre-infusion urine, with 15-25% of As(III), 35-55% of DMA, 25-30% of MMA and 1-5% of As(V), while three patients showed unexpected exceptions from typical excretion patterns of arsenic compounds (i) a high DMA/MMA ratio (factor 5.3), (ii) severe As(III) oxidation (10.2% As(III) converted to As(V)) or (iii) the presence of an excessive amount of As(III) (average 30.4% of total arsenic). Intriguing was the occurrence of post-infusion oxidation of As(III) to As(V) observed in almost all patients and being especially high (>40%) in patient with increased residual As(V). Results indicate that arsenic metabolites patterns can be unpredictable. Observed high levels of un-metabolised As(III) are a warning signal for side effects and for routine determination of arsenic metabolites during first days of treatment. High or low percentages of MMA or DMA did not show any observable effect on treatment results, while clear presence of post-infusion As(V) supports theoretical claims of in vivo oxidation (detoxification) of As(III) to As(V) associated with various metabolic processes. PMID- 26671505 TI - Effectiveness of Herpes Zoster Vaccine in Patients 60 Years and Older With End stage Renal Disease. AB - BACKGROUND: Unlike in a healthy population, the protection of herpes zoster (HZ) vaccine in end-stage renal disease (ESRD) patients might be insufficient, considering data demonstrating suboptimal response to other vaccines. The study evaluates the association between HZ vaccination and the subsequent HZ risk among ESRD patients. METHODS: This cohort study included ESRD patients age >=60 years who were enrolled in Kaiser Permanente Southern California. The vaccinated cohort included 582 patients who received HZ vaccine during 01/01/2007 through 12/31/2013. Each vaccinated patient was matched to five unvaccinated patients on age, sex, and dialysis duration. Subjects were passively followed through their electronic health records to identify HZ incidence. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) associated with vaccination. Kaplan-Meier estimates of the cumulative incidence were generated. RESULTS: The number of HZ cases was 16 in 1373 person-years (11.7 per 1000 person years; 95% CI, 7.1-19.0) among the vaccinated and 126 in 5644 person-years (22.3 per 1000 person-years; 95% CI, 18.7-26.6) among the unvaccinated. The 36-month cumulative risk of incident HZ was 4.1% and 6.6%, respectively. HZ vaccination was associated with a reduced risk of HZ (adjusted HR = 0.49; 95% CI, .29-.85). The reduced risk seems more prominent if the vaccine is given within two years of dialysis initiation. CONCLUSIONS: Among ESRD patients age >=60 years, receipt of HZ vaccine was associated with a lower incidence of HZ. In addition, HZ vaccination soon after the initiation of dialysis may provide greater protection. PMID- 26671506 TI - Toxicity evaluation of high-fluorescent rare-earth metal nanoparticles for bioimaging applications. AB - Research on nanometer-sized luminescent semiconductors and their biological applications in detectors and contrasting agents is an emergent field in nanotechnology. When new nanosize technologies are developed for human health applications, their interaction with biological systems should be studied in depth. Rare-earth elements are used in medical and industrial applications, but their toxic effects are not known. In this work, the biological interaction between terbium-doped gadolinium oxysulfide nanoparticles (GOSNPs) with human peripheral blood mononuclear cells (PBMC), human-derived macrophages (THP-1), and human cervical carcinoma cell (HeLa) were evaluated. The GOSNPs were synthetized using a hydrothermal method to obtain monodisperse nanoparticles with an average size of 91 +/- 9 nm. Characterization techniques showed the hexagonal phase of the Gd2 O2 S:Tb3+ free of impurities, and a strong green emission at lambdaemi = 544 nm produced by Tb3+ was observed. Toxic effects of GOSNPs were evaluated using cell viability, apoptosis, cell-cycle progression, and immunological response techniques. In addition, an Artemia model was used to assess the toxicity in vivo. Results indicated cell apoptosis in both types of cells with less sensitivity for PBMC cells compared to HeLa cells. In addition, no toxic effects were observed in the in vivo model of Artemia. Moreover, GOSNPs significantly reduced the activation and cell-cycle progression of PBMC and HeLa cells, respectively. Interestingly, an increase in proinflammatory cytokines was not observed. Our data suggest that fluorescence applications of GOSNPs for biolabeling are not toxic in primary immune cells and they may have an immunomodulatory effect. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 605-615, 2017. PMID- 26671507 TI - Combinational concentration gradient confinement through stagnation flow. AB - Concentration gradient generation in microfluidics is typically constrained by two conflicting mass transport requirements: short characteristic times (tau) for precise temporal control of concentration gradients but at the expense of high flow rates and hence, high flow shear stresses (sigma). To decouple the limitations from these parameters, here we propose the use of stagnation flows to confine concentration gradients within large velocity gradients that surround the stagnation point. We developed a modified cross-slot (MCS) device capable of feeding binary and combinational concentration sources in stagnation flows. We show that across the velocity well, source-sink pairs can form permanent concentration gradients. As source-sink concentration pairs are continuously supplied to the MCS, a permanently stable concentration gradient can be generated. Tuning the flow rates directly controls the velocity gradients, and hence the stagnation point location, allowing the confined concentration gradient to be focused. In addition, the flow rate ratio within the MCS rapidly controls (tau ~ 50 ms) the location of the stagnation point and the confined combinational concentration gradients at low flow shear (0.2 Pa < sigma < 2.9 Pa). The MCS device described in this study establishes the method for using stagnation flows to rapidly generate and position low shear combinational concentration gradients for shear sensitive biological assays. PMID- 26671508 TI - Assessment of Speckle-Tracking Echocardiography-Derived Global Deformation Parameters During Supine Exercise in Children. AB - Exercise echocardiography is an underutilized tool in pediatrics with current applications including detecting segmental wall abnormalities, assessing the utility of global ventricular function, and measuring pulmonary hemodynamics. No prior study has applied speckle-tracking echocardiography (STE) during exercise echocardiography in children. The aim of this study was to determine the feasibility of measuring speckle-tracking-derived peak systolic velocities, global longitudinal and circumferential strain, and global strain rates at various phases of exercise. Ninety-seven healthy children underwent cardiopulmonary exercise testing using supine cycle ergometry. The exercise stress test consisted of baseline pulmonary function testing, monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturations while subjects pedaled against a ramp protocol based on body weight. Echocardiographic measurements and specifically speckle-tracking analysis were performed during exercise at baseline, at a heart rate of 160 beats per minute and at 10 min after exercise. Peak systolic velocity, peak systolic strain, and peak systolic strain rate at these three phases were compared in the subjects in which all measurements were accurately obtained. We were able to complete peak velocity, strain, and strain rate measurements in all three exercise phases for 36 out of the 97 subjects tested. There was no significant difference between the feasibility of measuring circumferential versus longitudinal strain (p = 0.25, B corrected = 0.75). In the 36 subjects studied, the magnitude of circumferential strain values decreased from -18.3 +/- 4.8 to -13.7 +/- 4.0 % from baseline to HR 160 (p < 0.0001, B-corrected < 0.0001), before returning to -19.6 +/- 4.4 % at recovery (p = 0.19 when compared to baseline). Longitudinal strain did not vary significantly from baseline to HR 160 (from -17.7 +/- 4.4 to -16.6 +/- 4.4 %, p = 0.16); likewise the average recovery strain was no different from those values ( 18.4 +/- 3.6 %; p = 0.34). Peak circumferential and longitudinal strain rates increased from baseline to HR 160, but neither decreased to baseline levels after 10 min of recovery, which correlated with heart rate variations with exercise. We studied the effects of frame rate on deformation measurements and we observed no difference between measurements taken at lower (<60 frames per second, fps) and higher (>=60 fps) frame rates. This study shows that it is technically difficult to retrospectively measure peak velocities, strain, and strain rate in exercising pediatric subjects with STE. The majority of subjects that were excluded from the study had inadequate echocardiographic images when tachycardic from increased respiratory effort and body movements near peak exercise. Improvements in technique and higher image frame rates could make application of STE to pediatric cardiopulmonary testing more successful in the future. PMID- 26671510 TI - Zebrafish Social Behavior in the Wild. AB - Wild zebrafish exhibit a wide range of behavior. We found abundant wild zebrafish in flowing rivers and still water, in large, tightly-knit groups of hundreds of individuals, as well as in small, loose shoals. In two still-water populations, zebrafish were quite small in body size, common, and in tight groups of up to 22 fish. As in earlier laboratory studies, these zebrafish exhibited very low levels of aggression. In slowly flowing water in central India, zebrafish were relatively rare and gathered in small shoals (4-12 fish), often with other small fish, such as Rasbora daniconius. These stream zebrafish were larger in body size (27 mm TL) and much more aggressive than those in still water. In a second river population with much faster flowing water, zebrafish were abundant and again relatively large (21 mm TL). These zebrafish occurred in very large (up to 300 individuals) and tightly-knit (nearest-neighbor distances up to 21 mm) groups that exhibited collective rheotaxis and almost no aggression. This remarkable variation in social behavior of wild zebrafish offers an opportunity for future studies of behavioral genetics, development, and neuroscience. PMID- 26671509 TI - Association of the C2-CFB locus with non-infectious uveitis, specifically predisposed to Vogt-Koyanagi-Harada disease. AB - Complement component 2 (C2) and factor B (CFB) are regulators of complement system and involved in the alternative pathway, which have been identified to be associated with multiple immune-related diseases. This study aimed to investigate the association of these genes with non-infectious intermediate and posterior uveitis. A total of 260 Chinese non-infectious uveitis patients were recruited, including 97 patients with Vogt-Koyanagi-Harada disease (VKH), 70 patients with intermediate uveitis (IU) and 93 patients with Behcet's disease (BD). Two hundred and ninety-three normal control subjects were also recruited. Five SNPs across the C2/CFB region were selected and genotyped using TaqMan SNP Genotyping Assays. Association analysis was adjusted for gender and stratified by different subtypes. The CFB SNP rs1048709 was significantly associated with non-infectious uveitis [P corr = 0.01, OR 1.49 (allele model) and P corr = 0.04, OR 1.58 (dominant model), respectively], and similar association was also detected between rs1048709 and female uveitis patients (P corr = 0.01, OR 1.70 and P corr = 0.049, OR 184, respectively). Moreover, subgroup analyses showed that CFB rs1048709 was specifically associated with VKH, where significantly higher frequencies of A allele and AA homozygosity were observed in VKH patients compared with controls (P corr = 0.025 and P corr = 0.035, respectively), whereas none of these five SNPs was associated with IU or BD. In addition, a haplotype block across CFB (GTG) was significantly predisposed to uveitis with protective effect (OR 0.66, P corr = 0.048). Our results revealed a significant association of CFB with non-infectious uveitis, particularly predisposed to VKH disease. Genetic differences for uveitis could be gender-specific. PMID- 26671511 TI - Relationship between vitamin D levels and glucose tolerance in an adult population with cystic fibrosis. PMID- 26671512 TI - Using photo-initiated polymerization reactions to detect molecular recognition. AB - Widely used medical diagnostic devices and assays that sense the presence of a particular molecule in a bodily fluid often rely on either a nanoparticle label or an enzymatic reaction to generate a signal that is easily detectable. In many cases, it is desirable if the magnitude of the signal correlates with the concentration of the molecule of interest. Photo-initiated polymerization reactions are an alternative means of generating amplified signals that can be used to quantify biological molecules in complex fluids. In this case, the formation of a polymer, typically a cross-linked hydrogel, signifies the presence of the molecule of interest. This tutorial review explains how photo-initiated polymerization reactions have been used in a conditional manner to detect and quantify molecular recognition events. We weigh the advantages and disadvantages of using photo-initiated reactions in comparison with other approaches and highlight exciting directions and opportunities in this area. PMID- 26671513 TI - Branch Atheromatous Disease: A Clinically Meaningful, Yet Unproven Concept. AB - BACKGROUND: In 1989, Louis Caplan first used the term branch atheromatous disease (BAD) to describe an occlusion or stenosis at the origin of a deep penetrating artery of the brain, associated with a microatheroma or a junctional plaque, and leading to an internal capsule or pontine small infarct. BAD remained an understudied concept for decades. In recent years, the increasing diffusion of high-resolution magnetic resonance imaging (HRMRI) techniques brought new attention to the BAD debate. We have reviewed clinical studies dealing with BAD related stroke checking whether a univocal definition of BAD existed, as well as to what extent were consistently associated clinical and imaging features reported. SUMMARY: We conducted a search of the available literature published up to October 20, 2015 via PubMed using the following search terms: 'branch atheromatous disease,' 'intracranial branch atheromatous disease,' 'cerebral branch atheromatous disease,' combined with 'stroke.' Forty-six articles were included. We found discrepant definitions and a large variation among clinical features reported in BAD-related stroke patients: among others, a consistent association between BAD and any specific vascular risk factor profile was not detected. Despite this, early neurological deterioration (END) was consistently reported to occur frequently in such patients, although no clear-cut rate range or specific predictor or mechanism of progression was established. In a majority of the studies reporting imaging data, BAD diagnosis was not based on the selective site or type of arterial walls changes, but was inferred based on the vascular territory, size and/or shape of the ischemic lesion. Following the concept that these changes are seated proximally along the perforator artery, differently from to lipohyalinosis changes located distally, the consequent ischemic lesion was hypothesized to be larger in BAD than in lacunar infarcts. However, across reviewed studies, there was little consistency on the dimensional cutoff used to define BAD-related infarcts. In the last few years, a still limited number of studies using HRMRI techniques is providing preliminary proofs that atheromatous changes causing selective remodeling in the parent vessel and extending through the proximal segment of perforating vessel may subtend BAD. KEY MESSAGES: Our literature search showed the lack of a clear-cut definition of BAD, although BAD-related strokes were consistently considered a high risk of END. The use of high-resolution imaging techniques in the assessment of small subcortical strokes may represent the cornerstone in the perspective to better delimiting the boundaries of BAD as a nosological entity. PMID- 26671514 TI - Radiological and clinical outcomes of novel Ti/PEEK combined spinal fusion cages: a systematic review and preclinical evaluation. AB - PURPOSE: The primary objective of this paper was to provide a systematic review of the available clinical studies of Ti/PEEK combined cages in spinal interbody fusion surgeries, focusing on their radiological and clinical outcomes. A secondary aim was to provide a review and evaluation of the in vitro and preclinical studies reported on Ti/PEEK-coated implants. METHODS: A systematic search of the literature was performed in March 2015 via three databases: Medline, Embase and Cochrane library. The following key search terms were combined with synonyms to identify relevant articles: "spinal fusion," "PEEK," "titanium" and "cage." RESULTS: The novelty of this intervention translates into a paucity of clinical trials, albeit the results of the seven clinical studies that met the criteria for inclusion are promising. All studies reported rate of fusion as a primary outcome. Two studies reported slightly improved fusion in the experimental Ti/PEEK combination cohort, one study identical fusion (91.7 %) and three studies excellent fusion (96, 100 and 94 %) in the Ti/PEEK cohort, although no differences reached statistical significance. CONCLUSIONS: Clinical studies at this early stage demonstrate that Ti/PEEK implants are safe and efficacious, exhibiting similar fusion rates and clinical outcomes compared to the current standard PEEK. There is clinical evidence substantiating the improved radiographic fusion of Ti/PEEK, albeit the differences were not significant. This field is promising, gaining substantial popularity, and further clinical trials are needed in the future to establish Ti/PEEK cages as a mainstay of clinical practice. PMID- 26671517 TI - Itch and Pain Characteristics in Skin Carcinomas. PMID- 26671516 TI - The clinical management of abdominal ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: a review of current guidelines and recommendations. AB - Several pathogenic processes have been implicated in the development of abdominal ascites. Portal hypertension, most usually in the context of liver cirrhosis, can explain about 75% of the cases, whereas infective, inflammatory and infiltrative aetiologies can account for the rest. In this article, we discuss the consensus best practice as published by three professional bodies for the management of ascites, spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). The aim of this study was to compare available clinical guidelines and identify areas of agreement and conflict. We carried out a review of the guidance documentation published by three expert bodies including the British Society of Gastroenterology, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), as well as a wider literature search for ascites, SBP and HRS. Abdominal ultrasonography, diagnostic paracentesis and ascitic fluid cultures are recommended by all three guidelines, especially when there is strong clinical suspicion for infection. EASL and AASLD advocate the use of ascitic amylase and mycobacterial cultures/PCR when there is strong suspicion for tuberculosis and pancreatitis, respectively. Ascitic cytology can be useful when cancer is suspected and has a good diagnostic yield if performed correctly. EASL supports the use of urinary electrolytes for all patients; however, the British Society of Gastroenterology and AASLD only recommend their use for therapy monitoring. All three societies recommend cefotaxime as the antibiotic of choice for SBP and large-volume paracentesis for the management of ascites greater than 5 l in volume. For HRS, cautious diuresis, volume expansion with albumin and the use of vasoactive drugs are recommended. There appears to be good concordance between recommendations by the European, American and British guidelines for the management of ascites and the possible complications arising from it. PMID- 26671515 TI - Role of body composition and metabolic profile in Barrett's oesophagus and progression to cancer. AB - BACKGROUND AND AIMS: The aim of this study was to evaluate the risk for Barrett's oesophagus (BE) on the basis of body composition, metabolic pathways, adipokines and metabolic syndrome (MS), as well as their role in cancer progression. METHODS: In patients with and without BE at gastroscopy, data on MS, BMI, waist/hip ratio for abdominal obesity (AO) and body fat percentage by bioimpedance were obtained. Fasting plasma glucose, insulin, HbA1c, lipid, serum adiponectin and leptin levels were measured. The homoeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Histological findings for BE were correlated with the above parameters. Risk factors for BE identified using univariate analysis were entered into a multivariate logistic regression analysis. RESULTS: A total of 250 patients and 224 controls (F/M: 189/285, mean age 58.08+/-15.51 years) were enroled. In the BE and control groups, 39.6 versus 31.3% were overweight, 32 versus 22.8% were obese, 75.6 versus 51.3% had AO, and 28.1 versus 18.9% were metabolically obese, respectively. AO [odds ratio (OR) 3.08], increased body fat percentage (OR 2.29), and higher BMI (overweight: OR 2.04; obese: OR 2.26) were significantly associated with BE. A positive trend was found in Normal Weight Obese Syndrome (OR 1.69). MS was associated with BE (overweight: OR 3.05; obese: OR 5.2; AO: OR 8.08). Insulin levels (P=0.05) and HOMA-IR (P<0.001) were higher in BE. AO was the only independent risk factor associated with BE (OR 1.65; P=0.02) and high-grade dysplasia (OR 2.44) on multivariate analysis. CONCLUSION: AO was strongly associated with BE and dysplasia. BE was associated with MS and higher insulin/HOMA-IR, suggesting the activation of specific metabolic pathways in patients with altered body composition. PMID- 26671519 TI - ent-6,7-Secokaurane diterpenoids from Rabdosia serra and their cytotoxic activities. AB - Investigation of the hydrophobic extract of Rabdosia serra (Lamiaceae) led to the isolation of seven ent-6,7-secokaurane diterpenoids rabdosins E-K, along with twelve known ent-kaurane diterpenoids. Their structures were established by extensive spectroscopic analysis. The absolute configurations of rabdosins E, F, H and I were determined by single-crystal X-ray diffraction, with rabdosin E having a 3,20-epoxy group. These diterpenoids could be divided into two types according to their skeletons: rabdosins E-J are ent-6,20-epoxy-6,7-secokaur-1,7 olides, and rabdosin K is an ent-6,7-secokaur-7,20-olide. Cytotoxicity evaluation showed that serrin B, serrin A, isodocarpin and lushanrubescensin J exhibited weak to moderate cytotoxic activities (IC50<10MUM) against two human cancer cell lines. PMID- 26671518 TI - Mechanisms involved in extracellular matrix remodeling and arterial stiffness induced by hyaluronan accumulation. AB - BACKGROUND AND AIMS: Hyperglycemia induces hyaluronan (HA) accumulation in the vasculature. Excessive accumulation of HA around the vascular smooth muscle cells (VSMC) results in increased aortic stiffness and strength and accelerated atherosclerosis in ApoE(-)/(-) mice. We hypothesized that HA accumulation primes the vasculature for atherosclerosis by crosslinking and reorganizing the extracellular matrix (ECM) and by pushing VSMC differentiation towards a less mature phenotype. METHODS: Aortas from HAS-2 transgenic (Tg) mice and wild type mice were used for all experiments. Biomechanics and cross-sectional area measurements were performed before and after HA digestion. The vessel and ECM composition was examined by immunoblotting and electron microscopy. Primary VSMC cultures were examined by qPCR and thymidine incorporation. RESULTS: Tg mice aorta cross-sectional area was increased before (14%, p = 0.0148), but not after HA digestion (p = 0.3437). The increase in vessel stiffness (32%, p = 0.0217) and strength (31%, p = 0.0043) in the Tg aorta persisted after HA digestion. Crosslinking of HA by heavy chains from Inter-alpha-Inhibitor was increased (175%, p = 0.0006). The Tg VSMCs have the appearance of a synthetic phenotype supported by a 40% decrease in alpha-smooth muscle actin isoform X1 (p = 0.0296) and an increase in proliferation (63%, p = 0.0048) and osteoprotegerin production (133%, p = 0.0010) in cultured Tg VSMCs. CONCLUSIONS: Our results show that induced HA accumulation is followed by increased HA crosslinking and create a shift in VSMC phenotype and proliferation. These findings may provide a mechanism for how hyperglycemia through HA accumulation prime the vascular wall for cholesterol and leucocyte accumulation and development of atherosclerosis. PMID- 26671520 TI - Novel Mycobacterium avium Complex Species Isolated From Black Wildebeest (Connochaetes gnou) in South Africa. AB - A study was undertaken to isolate and characterize Mycobacterium species from black wildebeest suspected of being infected with tuberculosis in South Africa. This led to the discovery of a new Mycobacterium avium complex species, provisionally referred to as the Gnou isolate from black wildebeest (Connochaetes gnou). Sixteen samples from nine black wildebeest were processed for Mycobacterium isolation. Following decontamination, samples were incubated in an ordinary incubator at 37 degrees C on Lowenstein-Jensen slants and in liquid medium tubes using the BACTECTM MGITTM 960 system, respectively. Identification of the isolate was carried out by standard biochemical tests and using the line probe assay from the GenoType(r) CM/AS kit (Hain Lifescience GmbH, Nehren, Germany). The DNA extract was also analysed using gene sequencing. Partial gene sequencing and analysis of 16S rRNA gene, and 16S-23S rRNA (ITS), rpoB and hsp65 and phylogenetic analyses by searching GenBank using the BLAST algorithm were conducted. Phylogenetic trees were constructed using four methods, namely Bayesian inference, maximum likelihood, maximum parsimony and neighbour-joining methods. The isolate was identified as Mycobacterium intracellulare using the GenoType(r) CM/AS kit and as Mycobacterium avium complex (MAC) by gene sequencing. The gene sequence targeting all the genes, ITS, 16S rRNA, rpoB and hsp65 and phylogenetic analyses indicated that this isolate presented a nucleotide sequence different from all currently published sequences, and its position was far enough from other MAC species to suggest that it might be a new species. PMID- 26671521 TI - Hold your breath! PMID- 26671522 TI - Characterization of synovial mast cells in knee osteoarthritis: association with clinical parameters. AB - OBJECTIVE: To investigate the presence of mast cells in the osteoarthritic (OA) synovium and their association with clinical parameters in comparison with rheumatoid arthritis (RA) samples. METHOD: Synovial tissues of 56 symptomatic OA and 49 RA patients were obtained. Two to three paraffin slides were used to quantify inflammation using haematoxylin and eosin (H&E) staining (synovitis score 0-9), and numbers of mast cells (per 10 high-power fields) using double immunofluorescence for CD117 and tryptase. Average scores per patient were used for analysis. Knee radiographs of OA patients were scored according to the Kellgren and Lawrence (KL) system and pain was determined in OA patients at baseline by visual analogue scale (VAS). RESULTS: Median (range) of mast cells was significantly higher in OA samples 45 (1-168) compared to RA samples 4 (1-47) (P-value < 0.001), despite a lower median (range) synovitis score in OA (2.5 (0 6.0)) compared to 4.6 (0-8.0) in RA samples. The synovitis score was significantly correlated with the number of mast cells (in OA Spearman's rho (P value) 0.3 (0.023) and RA 0.5 (P-value < 0.001)). Interestingly, we observed a trend towards an association between the number of mast cells and an increased KL grade (P-value 0.05) in OA patients, independently of synovitis. No associations were found with self-reported pain. CONCLUSION: Prevalence of mast cells in OA synovial tissue is relatively high and associates with structural damage in OA patients, suggesting a role of mast cells in this disease. PMID- 26671523 TI - Implementing oral chemotherapy services in community pharmacies: a qualitative study of chemotherapy nurses' and pharmacists' views. AB - OBJECTIVES: Changes in health-care provision have led to cancer patients being offered oral chemotherapy in the community. Three levels of oral chemotherapy services have been proposed (levels 1, 2 and 3) with community pharmacies playing differing roles within them. This study aims to explore health-care professionals' views on oral chemotherapy services being delivered by community pharmacies and to gain insights into the barriers, facilitators and training/knowledge needs of community pharmacists with respect to providing them. METHODS: Qualitative semi-structured interviews were conducted with a purposive sample of three chemotherapy nurses, five oncology pharmacists and five community pharmacists. Data were analysed thematically using Framework Analysis. KEY FINDINGS: Findings for level 1 and 2 services included uncertainty on community pharmacists' professional responsibilities, the expertise of GPs in prescribing oral chemotherapy and the training and competency of community pharmacists. The lack of patient information, care and support provision was emphasised for all the models. Although level 1 was achievable in current practice, level 2 was considered the safest option, while level 3 was ideal but risky option. For all levels, training and education for community pharmacists and inter-professional issues were facilitators to oral chemotherapy services. The service environment, dispensing process-related constraints (access to blood test results and protocols) were significant barriers for levels 2 and 3. Advanced communication skills, patient education and counselling were identified as key areas for education and training for community pharmacists. CONCLUSION: The study suggests there are significant concerns and challenges associated with community pharmacies implementing any of the proposed levels of oral chemotherapy services. Educational and training opportunities for community pharmacists and the careful development of safe infrastructures will be essential in the future planning and implementation of any community pharmacy oral chemotherapy service. PMID- 26671526 TI - Decreased voltage-gated potassium currents in rat dorsal root ganglion neurons after chronic constriction injury. AB - Voltage-gated potassium channels (KV) regulate pain transmission by controlling neuronal excitability. Changes in KV expression patterns may thus contribute toward hyperalgesia following nerve injury. The aim of this study was to characterize KV current density in dorsal root ganglion (DRG) neurons following chronic constriction injury (CCI) of the right sciatic nerve, a robust model of post-traumatic neuropathic pain. The study examined changes in small-diameter potassium ion currents (<30 um) in neurons in the L4-L6 DRG following CCI by whole-cell patch-clamping and the association with post-CCI mechanical and thermal nociceptive thresholds. Compared with the control group, 7 days after CCI, the mechanical force and temperature required to elicit ipsilateral foot withdrawal decreased significantly, indicating tactile allodynia and thermal hyperalgesia. Post-CCI neurons had a significantly lower rheobase current and depolarized resting membrane potential than controls, suggesting KV current downregulation. Some ipsilateral DRG neurons also had spontaneous action potentials and repetitive firing. There was a 55% reduction in the total KV current density caused by a 55% decrease in the sustained delayed rectifier potassium ion current (IK) density and a 17% decrease in the transient A-type potassium ion current (IA) density. These results indicated that changes in DRG neuron IK and IA current density and concomitant afferent hyperexcitability may contribute toward neuropathic pain following injury. The rat CCI model may prove valuable for examining pathogenic mechanisms and potential therapies, such as KV channel modulators. PMID- 26671524 TI - Transcriptional elongation requires DNA break-induced signalling. AB - We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and gammaH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. gammaH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and gammaH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II. PMID- 26671525 TI - Western environment/lifestyle is associated with increased genome methylation and decreased gene expression in Chinese immigrants living in Australia. AB - INTRODUCTION: Several human diseases and conditions are disproportionally distributed in the world with a significant "Western-developed" vs. "Eastern developing" gradient. METHODS: We compared genome-wide DNA methylation of peripheral blood mononuclear cells in 25 newly arrived Chinese immigrants living in a Western environment for less than 6 months ("Newly arrived") with 23 Chinese immigrants living in the Western environment for more than two years ("Long term") with a mean of 8.7 years, using the Infinium HumanMethylation450 BeadChip. In a sub-group of both subject groups (n = 12 each) we also investigated genome wide gene expression using a Human HT-12 v4 expression beadChip. RESULTS: There were 62.5% probes among the total number of 382,250 valid CpG sites with greater mean Beta (beta) in "Long-term" than in "Newly arrived". In the regions of CpG islands and gene promoters, compared with the CpG sites in all other regions, lower percentages of CpG sites with mean methylation levels in "Long-term" greater than "Newly arrived" were observed, but still >50%. The increase of methylation was associated with a general decrease of gene expression in Chinese immigrants living in the Western environment for a longer period of time. After adjusting for age, gender and other confounding factors the findings remained. CONCLUSION: Chinese immigrants living in Australia for a longer period of time have increased overall genome methylation and decreased overall gene expression compared with newly arrived immigrants. PMID- 26671527 TI - Synthesis of Mesoionic Isoquinolines by Rhodium(III)-Catalyzed C-H Activation. AB - Hydroxyl-substituted benzaldimines underwent a Rh(III) -catalyzed C-H activation and annulation with alkynes to provide novel mesoionic isoquinoline derivatives in moderate to excellent yields using oxygen as an internal anion source. This simple and efficient approach has a broad substrate scope. PMID- 26671529 TI - In Memoriam. PMID- 26671528 TI - Evodiamine inhibits the proliferation of leukemia cell line K562 by regulating peroxisome proliferators-activated receptor gamma (PPARgamma) pathway. AB - Evodiamine, a quinolone alkaloid, is one of the major bioactive compounds of Evodia rutaecarpa Bentham (Rutaceae). It exhibits excellent biological activities, especially the anticancer activity. This study aims to investigate the effect of evodiamine on the proliferation of leukemia cell line K562 and to explore the underlying mechanism. The effect of evodiamine on K562 cells proliferation was analyzed by trypan blue dye exclusion assay and MTT assay. The expression levels of peroxisome proliferators-activated receptor gamma (PPARgamma), cyclin D1, and p21 were detected by western blot assay. The results demonstrated that evodiamine inhibited the proliferation and decreased the viability of K562 cells in a dose- and time-dependent manner. 2-Chloro-5-nitro-N phenylbenzamide (GW9662) and/or PPARgamma-siRNA pretreatment alleviated the cell growth suppression triggered by evodiamine. Meanwhile, evodiamine intervention elevated the expression of PPARgamma in K562 cells, while pretreatment with GW9662 attenuated the enhanced upregulation of PPARgamma expression induced by evodiamine. In addition, GW9662 and PPARgamma-siRNA pretreatment also significantly attenuated the downregulation of the cell cycle control protein cyclin D1 and the upregulation of cyclin-dependent kinase inhibitor p21 induced by evodiamine. In conclusion, PPARgamma signaling pathway may involve in the proliferation inhibition of evodiamine on K562 cells via inhibiting cylcin D1 and stimulating of p21. PMID- 26671531 TI - Early versus delayed erythropoietin for the anaemia of end-stage kidney disease. AB - BACKGROUND: Anaemia is a common complication in people with chronic kidney disease (CKD) and mainly develops as a consequence of relative erythropoietin (EPO) deficiency. Anaemia develops early in the course of disease and peaks among people with end-stage kidney disease (ESKD). Many types of EPO - also called erythropoiesis-stimulating agents (ESAs) - are used to treat anaemia in people with ESKD.ESAs have changed treatment of severe anaemia among people with CKD by relieving symptoms and avoiding complications associated with blood transfusion. However, no benefits have been found in relation to mortality rates and non cardiac fatal events, except quality of life. Moreover, a relationship between ESA use and increased cardiovascular morbidity and mortality in patients with CKD has been reported in studies with fully correcting anaemia comparing with partial anaemia correction. Until 2012, guidelines recommended commencing ESA treatment when haemoglobin was less than 11 g/dL; the current recommendation is EPO commencement when haemoglobin is between 9 and 10 g/dL. However, advantages in commencing therapy when haemoglobin levels are greater than 10 g/dL but less than 11 g/dL remain unknown, especially among older people whose life expectancy is limited, but in whom EPO therapy may improve quality of life. OBJECTIVES: To assess the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 8 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating at the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis. Studies comparing EPO with another EPO, placebo or no treatment were eligible for inclusion. DATA COLLECTION AND ANALYSIS: It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. For dichotomous outcomes (all-cause mortality, cardiovascular mortality, overall myocardial infarction, overall stroke, vascular access thrombosis, adverse effects of treatment, transfusion), we planned to use the risk ratio (RR) with 95% confidence intervals (CI). We planned to calculate the mean difference (MD) and CI 95% for continuous data (haemoglobin level) and the standardised mean difference (SMD) with CI 95% for quality of life if different scales had been used. MAIN RESULTS: Literature searches yielded 1910 records, of these 1534 were screened after duplicates removed, of which 1376 were excluded following title and abstract assessment. We assessed 158 full text records and identified 18 studies (66 records) that were potentially eligible for inclusion. However, none matched our inclusion criteria and were excluded. AUTHORS' CONCLUSIONS: We found no evidence to assess the benefits and harms of early versus delayed EPO for the anaemia of ESKD. PMID- 26671533 TI - Erratum: Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells. AB - A correction was made to Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells. There was a spelling error in one of the authors' surname. The author's name was corrected from: Veronica Rodriquez-Bravo to: Veronica Rodriguez-Bravo. PMID- 26671534 TI - Ligand Induced Anionic Cuprous Cyanide Framework for Cupric Ion Turn on Luminescence Sensing and Photocatalytic Degradation of Organic Dyes. AB - A new microporous luminescent coordination polymer [(CH3)2NH2].[Cu2(CN)3] (1) with channels occupied by dimethylamine cations was synthesized due to the inducing effect of 2-(2'-pyridyl)imidazole. Complex 1 exhibits bright-green emission in the solid state, and its emission intensity would be significantly enhanced, especially by DMAc and cupric ion after immersing the as-synthesized crystals of 1 into common organic solvents or methanol solutions of various metal ions. In addition, 1 exhibits photocatalytic activity for the degradation of RhB and MB under natural light and is stable during the photocatalysis process. Thus, 1 can act as a multifunctional material for selectively sensing of Cu(2+) and effectively photocatalytic degradation of dyes. PMID- 26671532 TI - A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity. AB - Both Epidermal Growth Factor Receptor (EGFR) and the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) play critical roles in tumorigenesis. We hypothesized co-targeting EGFR and VEGFR2 using a bispecific antibody might have significant therapeutic potential. Here,we designed and produced a human IgG-like bispecific antibody (Bi-Ab) based on the variable regions of cetuximab (an anti-EGFR antibody) and mAb-04 (an anti-VEGFR2 antibody developed in our lab) . The Bi-Ab was found to inhibit the proliferation, survival and invasion of cancer cells via ablating phosphorylation of receptor and downstream signaling. In vivo efficacy was demonstrated against established HT-29 and SKOV-3 xenografts grown in nude mice. Studies revealed our Bi-Ab was able to restrain xenografted tumor growth and prolong survival of mice through inhibiting cell proliferation,promoting apoptosis and anti-angiogenesis. In contrast to cetuximab or mAb-04 alone, our Bi Ab exhibits enhanced antitumor activity and has equal or slightly superior activity to their combination (Combi). It shows promise as a therapeutic agent, especially for use against tumors EGFR and/or VEGFR2 over-expressing malignancies. PMID- 26671535 TI - Bottom-up fabrication of graphene nanostructures on Ru(1010). AB - Investigations on the bottom-up fabrication of graphene nanostructures with 10, 10'-dibromo-9, 9'-bianthryl (DBBA) as a precursor on Ru(1010) were carried out using scanning tunnelling microscopy (STM) and density functional theory (DFT) calculations. Upon annealing the sample at submonolayer DBBA coverage, N = 7 graphene nanoribbons (GNRs) aligned along the [1210] direction form. Higher DBBA coverage and higher annealing temperature lead to the merging of GNRs into ribbon like graphene nanoflakes with multiple orientations. These nanoflakes show different Moire patterns, and their structures were determined by DFT simulations. The results showed that GNRs possess growth preference on the Ru(1010) substrate with a rectangular unit cell, and GNRs with armchair and zigzag boundaries are obtainable. Further DFT calculations suggest that the interaction between graphene and the substrate controls the orientations of the graphene overlayer and the growth of graphene on Ru(1010). PMID- 26671536 TI - Initial validation of a simple, nonbiological, mechanical ERCP training model for cannulation and stent placement. PMID- 26671538 TI - Safe guidewire-assisted method of over-the-scope clip delivery for bleeding in the small intestine. PMID- 26671537 TI - Utility of a stent pusher catheter as a "mini-overtube" in the endoscopic management of post-liver transplant biliary strictures. PMID- 26671539 TI - Esophageal perforation after epicardial ablation: an endoscopic approach. PMID- 26671540 TI - Endoscopic ultrasound (EUS)-guided duodenogastroenterostomy: why not do it from the other side? PMID- 26671541 TI - Synchronous pancreatic and gastric metastasis from an ovarian adenocarcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration. PMID- 26671542 TI - Direct peroral pancreatoscopy with a pediatric gastroscope for preoperative evaluation of the pancreatic duct in a patient with pancreatic intraductal papillary mucinous neoplasm. PMID- 26671543 TI - Endoscopic ultrasound-guided radiofrequency ablation of a pancreatic neuroendocrine tumor. PMID- 26671544 TI - Spatial and temporal regulation of sterol biosynthesis in Nicotiana benthamiana. AB - Nicotiana benthamiana was used as a model to investigate the spatial and developmental relationship between sterol synthesis rates and sterol content in plants. Stigmasterol levels were approximately twice the level in roots as that found in aerial tissues, while its progenitor sterol sitosterol was the inverse. When incorporation of radiolabeled precursors into sterols was used as measure of in vivo synthesis rates, acetate incorporation was similar across all tissue types, but approximately twofold greater in roots than any other tissue. In contrast, mevalonate incorporation exhibited the greatest differential with the rate of incorporation in roots approximately one-tenth that in apical shoots. Similar to acetate, incorporation of farnesol was higher in roots but remained fairly constant in aerial tissues, suggesting less regulation of the downstream sterol biosynthetic steps. Consistent with the precursor incorporation data, analysis of gene transcript and measurements of putative rate-limiting enzyme activities for 3-hydroxy-3-methylglutaryl-coenzyme A synthase (EC 2.3.3.10) and reductase (EC 1.1.1.34) showed the greatest modulation of levels, while the activity levels for isopentenyl diphosphate isomerase (EC 5.3.3.2) and prenyltransferases (EC 2.5.1.10 and EC 2.5.1.1) also exhibited a strong but moderate correlation with the development age of the aerial tissues of the plants. Overall, the data suggest a multitude of means from transcriptional to posttranslational control affecting sterol biosynthesis and accumulation across an entire plant, and point to some particular control points that might be manipulated using molecular genetic approaches to better probe the role of sterols in plant growth and development. PMID- 26671545 TI - Bioactive Secondary Metabolites Produced by the Oak Pathogen Diplodia corticola. AB - Three new lactones and a new fatty acid ester, named sapinofuranones C and D, diplopyrone B, and diplobifuranylone C, respectively, were isolated from Diplodia corticola, together with sphaeropsidins A and C, diplopyrone, diplobifuranylones A and B, diplofuranone A, and the (S,S)-enantiomer of sapinofuranone B. Sapinofuranones C and D, diplopyrone B, and diplobifuranylone C were characterized as (5S)-5-((1,S-1,6-dihydroxyhexa-2,4-dienyl)-dihydrofuran-2-one, 4,5-dihydroxy-deca-6,8-dienoic acid methyl ester, (5S)-5-hydroxy-6-(penta-1,3 dienyl)-5,6-dihydro-pyran-2-one, and 5'-((1R)-1-hydroxyethyl)-2',5'-dihydro-2H [2,2']bifuranyl-5-one by spectroscopic and chemical methods, respectively. The relative configuration of sapinofuranone C was assigned by X-ray diffraction analysis, whereas its absolute configuration was determined by applying the advanced Mosher's method to its 11-O-p-bromobenzoyl derivative. The same method was used to assign the absolute configuration to C-5 of diplopyrone B and to that of the hydroxyethyl of the side chain of diplobifuranylone C, respectively. The metabolites isolated were tested at 1 mg/mL on leaves of cork oak, grapevine cv. 'Cannonau', and tomato using the leaf puncture assay. They were also tested on tomato cuttings at 0.2, 0.1, and 0.05 mg/mL. Each compound was tested for zootoxic activity on Artemia salina L. larvae. The efficacy of sapinofuranone C and diplopyrone B on three plant pathogens, namely, Athelia rolfsii, Fusarium avenaceum, and Phytophthora nicotianae was also evaluated. In all phytotoxic assays only diplopyrone B was found to be active. It also showed strong inhibition on the vegetative growth of A. rolfsii and P. nicotianae. All metabolites were inactive in the assay performed for the zootoxic activity (A. salina) even at the highest concentration used (200 MUg/mL). Diplopyrone B showed a promising antioomycete activity for the control of Phytophthora spp. also taking into account the absence of zootoxic activity. PMID- 26671546 TI - Effect of Nanophyetus salmincola and Bacterial Co-Infection on Mortality of Juvenile Chinook Salmon. AB - The freshwater trematode Nanophyetus salmincola has been demonstrated to impair salmonid immune function and resistance to the marine pathogen Vibrio anguillarum, potentially resulting in ocean mortality. We examined whether infection by the parasite N. salmincola similarly increases mortality of juvenile Chinook Salmon Oncorhynchus tshawytscha when they are exposed to the freshwater pathogens Flavobacterium columnare or Aeromonas salmonicida, two bacteria that juvenile salmonids might encounter during their migration to the marine environment. We used a two-part experimental design where juvenile Chinook Salmon were first infected with N. salmincola through cohabitation with infected freshwater snails, Juga spp., and then challenged with either F. columnare or A. salmonicida. Cumulative percent mortality from F. columnare infection was higher in N. salmincola-parasitized fish than in nonparasitized fish. In contrast, cumulative percent mortality from A. salmonicida infection did not differ between N. salmincola-parasitized and nonparasitized groups. No mortalities were observed in the N. salmincola-parasitized-only and control groups from either challenge. Our study demonstrates that a relatively high mean intensity (>200 metacercariae per posterior kidney) of encysted N. salmincola metacercariae can alter the outcomes of bacterial infection in juvenile Chinook Salmon, which might have implications for disease in wild fish populations. PMID- 26671547 TI - The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor. AB - High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme-linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL-17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA like model. PMID- 26671548 TI - Structural dependence of in vitro cytotoxicity, oxidative stress and uptake mechanisms of poly(propylene imine) dendritic nanoparticles. AB - The in vitro cytotoxic and intracellular oxidative stress responses to exposure to poly(propylene imine) (PPI) dendritic nanoparticles of increasing generation (number of repeated branching cycles) (G0-G4) were assessed in an immortal non cancerous human keratinocyte cell line (HaCaT). Confocal fluorescence microscopy with organelle staining was used to explore the uptake and intracellular trafficking mechanisms. A generation- and dose-dependent cytotoxic response was observed, increasing according to generation and, therefore, number of surface amino groups. A comparison of the cytotoxic response of G4 PPI and the related G4 poly(amido amine) dendrimer indicates that the PPI with the same number of surface amino groups elicits a significantly higher cytotoxic response. The trend of cytotoxicity versus dendrimer generation and, therefore, size is discontinuous in the region of G2, however, indicating a difference in uptake mechanism for higher compared to lower generations. Whereas the higher generations elicit an oxidative stress response at short exposure times, the lower generations indicate an antioxidant response. Confocal microscopy indicates that, whereas they are prominent at early exposure times for the larger PPI dendrimers, no evidence of early stage endosomes was observed for lower generations of PPI. The results are consistent with an alternative uptake mechanism of physical diffusion across the semipermeable cell membrane for the lower generation dendrimers and are discussed in terms of their implications for predictive models for nanotoxicology and design strategies for nanomedical applications. PMID- 26671549 TI - The effects of lung and prostate cancer bone metastasis on serum osteoprotegerin levels: a meta-analysis. AB - Bone metastasis leads to skeletal-related events in final-stage cancer patients. The incidence of prostate and lung cancers increases yearly; these cancers readily invade the bone. Some recent studies have found that serum osteoprotegerin (OPG) levels may be altered in patients with bone metastasis, whereas other reports have produced inconsistent findings. Hence, we conducted a meta-analysis to examine the effects of lung and prostate cancer on serum OPG levels. A systematic literature search was conducted using PubMed, Medline, and CNKI to identify relevant studies. A total of 11 studies were included. The standardized mean difference (SMD) and 95% confidence interval (95% CI) of the bone metastasis (BM) group, the non-bone metastasis (BM-) group and healthy controls were calculated. In prostate cancer, serum OPG levels in the BM group were higher than in the BM- group and healthy controls. Additionally, no significant difference in serum OPG levels was found between the BM- group and healthy controls. In lung cancer, serum OPG levels in the BM and BM- groups were significantly increased compared with healthy controls. However, no significant difference in serum OPG levels was found between the BM and BM- groups. Studies with larger sample sizes are required to confirm these findings. PMID- 26671550 TI - Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy. AB - Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT. PMID- 26671551 TI - Frontal white matter changes and aggression in methamphetamine dependence. AB - Chronic methamphetamine (MA) use can lead to white matter (WM) changes and increased levels of aggression. While previous studies have examined WM abnormalities relating to cognitive impairment, associations between WM integrity and aggression in MA dependence remain unclear. Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy controls. A region of interest (ROI) approach using tract based spatial statistics (TBSS) in FSL was performed. We compared fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (lambda?) and perpendicular diffusivity (lambda?) in WM tracts of the frontal brain. A relationship of WM with aggression scores from the Buss & Perry Questionnaire was investigated. Mean scores for anger (p < 0.001), physical aggression (p = 0.032) and total aggression (p = 0.021) were significantly higher in the MA group relative to controls. ROI analysis showed increased MD (U = 439.5, p = 0.001) and lambda? (U = 561.5, p = 0.021) values in the genu of the corpus callosum, and increased MD (U = 541.5, p = 0.012) values in the right cingulum in MA dependence. None of the WM changes were significantly associated with aggression scores. This study provides evidence of frontal WM changes and increased levels of aggression in individuals with MA dependence. The lack of significant associations between WM and aggressive behaviour may reflect methodological issues in measuring such behaviour, or may indicate that the neurobiology of aggression is not simply correlated with WM damage but is more complex. PMID- 26671553 TI - The role of microRNAs in the adrenocortical carcinomas. AB - MicroRNAs (miRNAs) are a group of small, non-protein-coding RNAs that inhibit gene expressions through binding their 3'-UTR regions. Each miRNA can regulate a number of target genes and play crucial roles in a lot of biological processes including organogenesis, hematopoiesis, cell development, proliferation, and invasion. Deregulated expression of miRNAs has been found to be associated with initiation and development of tumors. Increasing evidences showed that miRNAs play a crucial role in adrenocortical carcinomas (ACCs). Aberrant miRNA expression may contribute to ACC carcinogenesis, and it can act as tumor suppressive or oncogenic miRNAs. In this review, we reviewed the recent studies available on ACC-associated miRNAs. We try to summarize the contribution of miRNAs to the initiation and development of ACCs. PMID- 26671552 TI - Gamma-Ionizing radiation-induced activation of the EGFR-p38/ERK-STAT3/CREB-1-EMT pathway promotes the migration/invasion of non-small cell lung cancer cells and is inhibited by podophyllotoxin acetate. AB - Here, we report a new intracellular signaling pathway involved in gamma-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion and migration of A549 cells (a non-small cell lung cancer (NSCLC) cell line). Our results revealed that IR increased the invasion/migration of A549 cells, and this effect was decreased by 10 nM PA treatment. PA also inhibited the expressions/activities of matrix metalloprotase (MMP) -2, MMP-9, and vimentin, suggesting that PA could block the IR-induced epithelial-mesenchymal transition (EMT). The IR-induced increases in invasion/migration were associated with the activation of EGFR-AKT, and PA inhibited this effect. P38 and p44/42 ERK were also involved in IR-induced invasion/migration, and combined treatments with PA plus inhibitors of each MAPK synergistically blocked this invasion/migration. In terms of transcription factors (TFs), IR-induced increases in cyclic AMP response element-binding protein-1 (CREB-1) and signal transducer and activator of transcription 3 (STAT3) increased invasion/migration and EMT. PA also inhibited these transcription factors and then blocked IR-induced invasion/migration. Collectively, these results indicate that IR induces cancer cell invasion/migration by activating the EGFR-p38/ERK-CREB-1/STAT3-EMT pathway and that PA blocks this pathway to inhibit IR-induced invasion/migration. PMID- 26671554 TI - The prediction of survival of patients with gastric cancer with PD-L1 expression using contrast-enhanced ultrasonography. AB - Gastric cancer is the one of the most common cancers around the world. The prognosis of gastric cancer remains poor, due to the biological characteristics of the primary tumor as well as the recurrence after treatment. Accumulating evidence suggests the implication of programmed death ligand-1 (PD-L1) in the pathogenesis and prognosis of cancer. This study aimed to explore the CEUS as a valuable tool to improve the assessment of the therapeutic effect of the PD-L1 blocker in the treatment of gastric cancer. A total number of 105 patients with gastric cancer were enrolled in this study from June 2008 to December 2011 in our hospital. The association of PD-L1 expression level (105 cases) and CEUS parameters (100 cases) with the prognosis of gastric cancer was examined. The results showed that PD-L1-positive staining was associated with the depth of invasion, differentiation, and poor prognosis of patients with gastric cancer. The CEUS intensity (positive) exhibited poor prognosis compared to the negative counterpart. Moreover, PD-L1 and CEUS co-positivity was significantly related to a poor prognosis. The characteristic of ultrasonography images correlated with the expression of PD-L1 (r = 0.46, P = 0.0003). Collectively, the mean intensity of contrast-enhanced ultrasonography is a useful predictor in the PD-L1 expression in gastric cancer. The ultrasonography and CEUS parameter could be considered as the predictor of response to PD-L1 blocker treatment in the clinical practice. PMID- 26671555 TI - Perceptions towards electronic cigarettes for smoking cessation among Stop Smoking Service users. AB - OBJECTIVES: Electronic cigarettes (e-cigarettes) are promoted as smoking cessation tools, yet they remain unavailable from Stop Smoking Services in England; the debate over their safety and efficacy is ongoing. This study was designed to explore perceptions and reasons for use or non-use of electronic cigarettes as smoking cessation tools, among individuals engaged in Stop Smoking Services. METHODS: Semi-structured telephone interviews were undertaken with twenty participants engaged in Stop Smoking Services in the north-west of England. Participants comprised of both individuals who had tried e-cigarettes (n = 6) and those who had not (n = 14). Interviews were digitally recorded and transcribed verbatim. The transcripts were subject to thematic analysis, which explored participants' beliefs and experiences of e-cigarettes. RESULTS: A thematic analysis of transcripts suggested that the following three superordinate themes were prominent: (1) self-efficacy and beliefs in e-cigarettes; (2) e cigarettes as a smoking cessation aid; and (3) cues for e-cigarette use. Participants, particularly never users, were especially concerned regarding e cigarette efficacy and safety. Overall, participants largely expressed uncertainty regarding e-cigarette safety and efficacy, with some evidence of misunderstanding. CONCLUSIONS: Evidence of uncertainty and misunderstanding regarding information on e-cigarettes highlights the importance of providing smokers with concise, up-to-date information regarding e-cigarettes, enabling smokers to make informed treatment decisions. Furthermore, identification of potential predictors of e-cigarette use can be used to inform Stop Smoking Services provision and future research. STATEMENT OF CONTRIBUTION: What is already known on this subject? Research suggests that e-cigarettes may help smokers quit smoking, but further studies are needed. Electronic cigarette use in Stop Smoking Services has increased substantially in recent years, although e cigarettes are currently not regulated. There is debate within the academic community regarding e-cigarette efficacy and safety. What does this study add? Service users interviewed in the current study felt uncertain regarding e cigarette efficacy and safety. E-cigarette ever users viewed e-cigarettes as effective and safe, more often than never users. Accurate and up-to-date education will enable service users to make informed treatment decisions. PMID- 26671556 TI - Passages 2016. PMID- 26671557 TI - Context, Community, and a Culture of Health: Perspectives From the U.S.-Mexico Border Region. PMID- 26671558 TI - Acceptability of a Virtual Patient Educator for Hispanic Women. AB - There are few Spanish language interactive, technology-driven health education programs. Objectives of this feasibility study were to (a) learn more about computer and technology usage among Hispanic women living in a rural community and (b) evaluate acceptability of the concept of using an embodied conversational agent (ECA) computer application among this population. A survey about computer usage history and interest in computers was administered to a convenience sample of 26 women. A sample video prototype of a hospital discharge ECA was administered followed by questions to gauge opinion about the ECA. Data indicate women exhibited both a high level of computer experience and enthusiasm for the ECA. Feedback from community is essential to ensure equity in state of the art dissemination of health information. PMID- 26671559 TI - Ending Intimate Partner Violence Among Latinas: Aguantando No Mas. AB - This study examined the psychological and sociocultural processes of Latinas leading to the decision to end an abusive intimate partner relationship using the qualitative method of grounded theory. There are few qualitative studies describing the experience from the perspective of Latinas and what factors may play a role in the decision-making process. Twenty-four participants were recruited from 3 agencies providing domestic violence services. Open-ended semistructured interviews and data analysis were conducted primarily in Spanish. Aguantando no mas or no longer choosing to endure emerged from this study as the central dimension in describing the decisional process of ending an abusive relationship. The participants' decision to no longer aguantar, or endure, occurred through a series of encounters with allies, the loss of hope that their partner was going to change, accessing available resources, and the final realization that their own well-being and of the children was being adversely affected by the abuse. The theoretical framework developed from this study can guide mental health professionals and health care providers in identifying areas for interventions for Latinas to ensure the safety and well-being of Latinas and their children. PMID- 26671560 TI - Insurance Status Is a Greater Barrier Than Income or Acculturation to Chronic Disease Screening in the Mexican Origin Population in El Paso, Texas. AB - The purpose of this study was to determine the association between income, insurance status, acculturation, and preventive screening for diabetes, high blood pressure, and cholesterol in Mexican American adults living in El Paso, Texas. This is a secondary data analysis using data from El Paso, Texas, that was collected between November 2007 and May 2009. Bivariate and stepwise regression analysis was used to determine the relationships between income, insurance, and acculturation factors on preventive screenings. Findings indicate that insurance status was associated with blood pressure check, blood sugar check, cholesterol screening, and any preventive screening. The association for income $40,000 + was explained by insurance. The only significant acculturation variable was language use for cholesterol. Disparities in preventive health screening in Mexican Americans were associated with primary insurance coverage in El Paso, Texas. With the border region being among the most medically underserved and underinsured areas in the United States, the results from this study suggest policy efforts are essential to ensure equal access to resources to maintain good health. Intervention efforts may include increasing awareness of enrollment information for insurance programs through the Affordable Care Act. PMID- 26671561 TI - Latino Teen Theater: A Theater Intervention to Promote Latino Parent-Adolescent Sexual Communication. AB - Latina teen pregnancy rates continue to be a health disparity in the United States. This study evaluated a parenting intervention using interactive theater to facilitate Latino parent-adolescent communication about sexuality and pregnancy prevention. The intervention, conducted in Spanish and with teen actors, consisted of scenes involving the audience. Fifty-nine parents participated in this 3-month prospective study. Spanish measures of comfort with communication, general communication, and parent-child sexual communication were employed comparing paired t tests for each scale. Acceptability of the intervention was assessed and demonstrated. Eighty-six percent of parents used information from the performance to talk to their child. Improvements in general communication (p < .02), sexual communication (p < .001), and comfort (p < .001) occurred. Interactive theater is an innovative approach to facilitate Latino parent communication about sexuality and pregnancy prevention. PMID- 26671562 TI - A Voice and a Vote: The Advisory Board Experiences of Spanish-Speaking Latina Mothers. AB - Latino children experience disparities in health care access and quality. Family advisory groups for clinics and hospitals may be one way to address disparities. We implemented and sustained an advisory board whose parent participants were exclusively limited-English proficient Latina mothers. As part of the board evaluation, we conducted semistructured individual interviews with parent participants during initial participation and after the final board meeting of the year. Members were satisfied with their board participation in both initial and follow-up interviews. They reported that board membership was an important way to improve clinic services and a unique opportunity for Latinos in the community. Experiences of discrimination and marginalization in health care settings were a theme across interviews. Members reported board membership countered these negative experiences. An advisory board including Spanish speaking parents is an opportunity to engage vulnerable populations, which may result in broader impact on health care disparities. PMID- 26671563 TI - Halofuginone Synergistically Enhances Anti-Proliferation of Rapamycin in T Cells and Reduces Cytotoxicity of Cyclosporine in Cultured Renal Tubular Epithelial Cells. AB - Both rapamycin (RAPA) and cyclosporin A (CsA) are commonly used for immunosuppression, however their adverse side effects limit their application. Thus, it is of interest to develop novel means to enhance or preserve the immunosuppressive activity of RAPA or CsA while reducing their toxicity. Halofuginone (HF) has been recently tested as a potential immunosuppressant. This study investigated the interaction of HF with RAPA or with CsA in cell cultures. Cell proliferation in cultures was determined using methylthiazol tetrazolium assay, and cell apoptosis assessed by flow cytometric analysis and Western blot. The drug-drug interaction was determined according to Loewe's equation or Bliss independence. Here, we showed that addition of HF to anti-CD 3 antibody stimulated splenocyte cultures induced synergistic suppression of T cell proliferation in the presence of RAPA, indicated by an interaction index (gamma) value of < 1.0 between HF and RAPA, but not in those with CsA. The synergistic interaction of RAPA with HF in the suppression of T cell proliferation was also seen in a mixed lymphocyte reaction and Jurkat T cell growth, and was positively correlated with an increase in cell apoptosis, but not with proline depletion. In cultured kidney tubular epithelial cells, HF attenuated the cytotoxicity of CsA. In conclusion, these data indicate that HF synergistically enhances anti-T cell proliferation of RAPA and reduces the nephrotoxicity of CsA in vitro, suggesting the potential use of HF for enhancing anti-T cell proliferation of RAPA and reducing CsA-mediated nephrotoxicity. PMID- 26671565 TI - Description and evaluation of four ultrasound-guided approaches to aid spinal canal puncture in dogs. AB - OBJECTIVE: To describe four ultrasound-guided approaches to the lumbar and thoracic spine to aid spinal canal puncture in the dog and to evaluate the feasibility of the technique. STUDY DESIGN: Prospective experimental study. ANIMAL POPULATION: Two canine cadavers. METHODS: In the first part of the study, the ultrasonographic appearance of the interlaminar space in the lumbosacral, lumbar and thoracic regions was described. In the second part of the study, four operators attempted a real-time, ultrasound-guided approach to the vertebral canal. Each operator performed the technique 20 times in total: five times at the lumbosacral junction, five in the thoracic region, five in the lumbar region with an in-plane approach, and five in the lumbar region with an out-of-plane approach. Computed tomography (CT) was used to confirm the position of the needle. The procedure was considered successful when the tip of the needle was observed within the vertebral canal. The success rate was calculated for each approach and operator. Fisher's exact test was used to compare differences between approaches and operators. RESULTS: In all cases, visualization of a ventral, parallel and straight hyperechoic line (floor of the vertebral canal) was considered a necessary prerequisite for successful positioning of the needle within the vertebral canal. A straight hyperechoic line (ligamentum flavum or dura mater) closer to the ultrasound probe was visualized in both the median lumbosacral approach and the transverse lumbar approach. The success rate overall was 81%; for the lumbosacral approach, 100%; for the thoracic approach, 80%; for the in-plane lumbar approach 95%; and for the out-of-plane lumbar approach, 45%. These differences were statistically significant (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The sonographic description of these approaches was considered adequate for performing spinal canal puncture. In-plane techniques achieved a higher success rate than out-of-plane ones. Further studies are needed to evaluate them in a clinical setting. PMID- 26671564 TI - Novel Essential Role of Ethanol Oxidation Genes at Low Temperature Revealed by Transcriptome Analysis in the Antarctic Bacterium Pseudomonas extremaustralis. AB - Temperature is one of the most important factors for bacterial growth and development. Cold environments are widely distributed on earth, and psychrotolerant and psychrophilic microorganisms have developed different adaptation strategies to cope with the stress derived from low temperatures. Pseudomonas extremaustralis is an Antarctic bacterium able to grow under low temperatures and to produce high amounts of polyhydroxyalkanoates (PHAs). In this work, we analyzed the genome-wide transcriptome by RNA deep-sequencing technology of early exponential cultures of P. extremaustralis growing in LB (Luria Broth) supplemented with sodium octanoate to favor PHA accumulation at 8 degrees C and 30 degrees C. We found that genes involved in primary metabolism, including tricarboxylic acid cycle (TCA) related genes, as well as cytochromes and amino acid metabolism coding genes, were repressed at low temperature. Among up regulated genes, those coding for transcriptional regulatory and signal transduction proteins were over-represented at cold conditions. Remarkably, we found that genes involved in ethanol oxidation, exaA, exaB and exaC, encoding a pyrroloquinoline quinone (PQQ)-dependent ethanol dehydrogenase, the cytochrome c550 and an aldehyde dehydrogenase respectively, were up-regulated. Along with RNA-seq experiments, analysis of mutant strains for pqqB (PQQ biosynthesis protein B) and exaA were carried out. We found that the exaA and pqqB genes are essential for growth under low temperature in LB supplemented with sodium octanoate. Additionally, p-rosaniline assay measurements showed the presence of alcohol dehydrogenase activity at both 8 degrees C and 30 degrees C, while the activity was abolished in a pqqB mutant strain. These results together with the detection of ethanol by gas chromatography in P. extremaustralis cultures grown at 8 degrees C support the conclusion that this pathway is important under cold conditions. The obtained results have led to the identification of novel components involved in cold adaptation mechanisms in this bacterium, suggesting for the first time a role of the ethanol oxidation pathway for bacterial growth at low temperatures. PMID- 26671566 TI - Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts. AB - Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector-mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity. PMID- 26671567 TI - Auditory perception and word recognition in Cantonese-Chinese speaking children with and without Specific Language Impairment. AB - Auditory processing and spoken word recognition difficulties have been observed in Specific Language Impairment (SLI), raising the possibility that auditory perceptual deficits disrupt word recognition and, in turn, phonological processing and oral language. In this study, fifty-seven kindergarten children with SLI and fifty-three language-typical age-matched controls were assessed with a speech-gating task to measure spoken word recognition, psychophysical tasks to measure auditory Frequency Modulation (FM) detection and Frequency Discrimination (FD), and standardized psychometric tests of phonological processing and oral language. As a group, children with SLI took significantly longer than language typical controls to recognize words with high neighborhood density, perhaps reflecting subpar phonological representations. FM, but not FD, was significantly worse in SLI. However, while both poorer speech-gating performance and poorer auditory thresholds (FM) were evident in SLI, spoken word recognition did not mediate any relation between auditory perception and either phonological processing or oral language. PMID- 26671568 TI - Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus. AB - Foot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats' cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene, and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV. PMID- 26671569 TI - Prevalence of HIV infection among burn patients: is there a relationship with patients' outcomes? AB - The aim of the present study was to determine the prevalence of human immunodeficiency virus (HIV) infection among acute burn patients and its impacts on patient's outcomes in an Iranian burn care hospital. A cross-sectional study was conducted in a tertiary burn care hospital in Iran, retrospectively reviewing the data records of all patients admitted between February 2011 and February 2012. The HIV status of all the patients was assessed in relation to clinical outcomes and the patient's prognosis. A total of 969 patients were included in this study. Five patients (0.5%) were HIV positive, and all of them were male. Mean burn area was significantly larger in HIV-positive patients than the healthy group (P < 0.05). HIV-positive patients had a longer period of hospitalisation than HIV-negative patients (23.2 +/- 16.3 versus 13.1 +/- 14.6, P = 0.008). Nonetheless, the average number of procedures and the mortality rate did not significantly differ between the study groups (P > 0.05). Comparison of age, sex and burn extent between HIV-positive patients and HIV-negative cases also revealed similar results. Prevalence of HIV infection among our burn population was 0.5%; thus, HIV status may be related with more extensive injuries and longer hospital stays. PMID- 26671570 TI - Geriatric tibial plateau fractures: Clinical features and surgical outcomes. AB - BACKGROUND: Operative treatment of geriatric tibial plateau fractures is challenging and controversial. There are few studies focusing on the clinical features and operative outcomes of tibial plateau fractures in the elderly. Hence, this study aimed to investigate the clinical features and operative results of these fractures. METHODS: Thirty-three displaced tibial plateau fractures in patients >65 years old (mean age: 72.1 years, range: 65-94 years) were treated operatively. We investigated the mechanisms of injury, fracture types according to the Schatzker classification, incidences of soft tissue injury, and postoperative complications. Clinical and radiographic data were analyzed in 23 patients at the last follow-up. The mean follow-up period was 4.0 years (range: 1-13 years). Twenty-one patients were treated with open reduction and internal fixation and evaluated using the Rasmussen clinical and radiologic scores. Two patients with advanced osteoarthritis were treated primarily with total knee arthroplasty and assessed using the Japanese Orthopaedic Association score for the knee osteoarthritis. RESULTS: Twenty-four patients (72.7%) were injured by low-energy trauma such as a simple fall. Four patients had compartment syndrome and required fasciotomies. Rasmussen clinical and radiologic scores were satisfactory in 85.7% and 81.0% of patients, respectively. Two patients treated primarily with total knee arthroplasty showed no radiologic abnormality, and their Japanese Orthopaedic Association scores were both 70 points. CONCLUSIONS: Geriatric tibial plateau fractures, although mostly due to low-energy trauma, were often accompanied with severe comminution and compartment syndrome. Postoperative results of open reduction and internal fixation for this population were relatively good. Therefore, primary total knee arthroplasty should only be considered for well-selected patients. PMID- 26671571 TI - Relation between the stand-up test and gait speed, knee osteoarthritis, and osteoporosis using calcaneal quantitative ultrasound - Cross-sectional study. AB - OBJECTIVE: The aim of the present study was to clarify the relationship between the stand-up test and gait speed, knee osteoarthritis (OA), and osteoporosis using calcaneal quantitative ultrasound. STUDY DESIGN: Cross-sectional study. METHODS: A total of 185 subjects (55 men, 130 women) aged >=40 years (mean age, 63.7 years; range, 40-79 years) were evaluated using the stand-up test to screen for locomotive syndrome. We also assessed OA of the knee using X-rays and a subjective questionnaire, physical characteristics, 6-m gait speed (m/s), and bone density. If results on the stand-up test were worse than benchmarks by age group (i.e., the height at which 50% of each age group could stand-up), the subject was defined as having a risk for locomotive syndrome (L group). We analyzed the relationship between the stand-up test and other variables. RESULTS: Of 185 subjects, 50 (27.0%) were classified into the L group. In univariate analysis, there were significant differences between the L group and non-L group in bone density (p < 0.001), gait speed (p < 0.001), osteoporosis (p < 0.001), slow gait speed group (SGSG) (cut off 1 m/s), and Japanese knee osteoarthritis measure score. Multivariate logistic regression analysis adjusted for age, height, weight, and gender showed a significant association between the stand-up test and bone density (OR 0.960, 95% confidence interval (95% CI) 0.927-0.994), gait speed (m/s) (OR 0.073, 95% CI 0.016-0.342), osteoporosis (OR 3.710, 95% CI 1.410-9.764), and SGSG (OR 7.849, 95% CI 1.628-37.845). CONCLUSIONS: The stand-up test to screen for the risk for locomotive syndrome was associated with bone density, gait speed, osteoporosis, SGSG. The stand-up test is an easy test to use to screen for possible disability among the elderly. PMID- 26671572 TI - Analysis of scientific output by spine surgeons from Japan: January 2000 to December 2013. AB - BACKGROUND: Over the last decade, the growing body of work on spine pathology has led to developments and refinements in the areas of basic science, diagnosis and treatment of a variety of spine conditions. Scientific publications have a global impact on the international scientific community as they share vital information that can be applied by physicians worldwide to solve their everyday medical problems. The historical background of scientific publication in journals in Japan on the subject of spine is unclear. METHODS: We performed a literature search for publications by Japanese spine surgeons regarding spine or spinal cord topics using an online database: Pubmed.gov (http://www.ncbi.nlm.nih.gov/pubmed/). The results were stored and analyzed at the Laboratory of Clinical Studies and Basic Models of Spinal Disorders of the University of Caxias do Sul. Results were limited to articles published from January 2000 to December 2013. The search terms used were "Japan" AND ("spine" OR "spinal diseases" OR "spinal cord" OR "spinal cord diseases" OR "vertebroplasty" OR "arthrodesis" OR "discectomy" OR "foraminotomy" OR "laminectomy" OR "denervation" OR "back injuries"). Japanese spine surgeons were defined as spine surgeons from orthopedic or neurosurgical specialties where the publication was affiliated with Japanese services. RESULTS: A total of 16,140 articles were identified by the Medline search. Most of the articles were excluded based on information provided in the title and abstract as they were not related to spine surgery. This study comprised 1768 articles published in the Medline database by Japanese spine surgeons from 2000 to 2013. The number of publications rose in a linear fashion, with the number of papers published increasing by 5.4 per year (p = 0.038). In recent years the publications were increasingly performed in conjunction with the neurosurgery and orthopedics specialties. CONCLUSIONS: This study showed a clear increase in publications (on Medline) by Japanese spine surgeons over the last 14 years. While this is a positive development, there is also cause for concern as there is some evidence that the number of young scientists is declining in Japan. Special attention to educating researchers and improving resources for research is crucial to further increase the number and quality of Japanese publications. PMID- 26671573 TI - Peridomestic Infection as a Determining Factor of Dengue Transmission. AB - BACKGROUND: The study of endemic dengue transmission is essential for proposing alternatives to impact its burden. The traditional paradigm establishes that transmission starts around cases, but there are few studies that determine the risk. METHODS: To assess the association between the peridomestic dengue infection and the exposure to a dengue index case (IC), a cohort was carried out in two Mexican endemic communities. People cohabitating with IC or living within a 50-meter radius (exposed cohort) and subjects of areas with no ICs in a 200 meter radius (unexposed cohort) were included. RESULTS: Exposure was associated with DENV infection in cohabitants (PRa 3.55; 95%CI 2.37-5.31) or neighbors (PRa 1.82; 95%CI 1.29-2.58). Age, location, toilets with no direct water discharge, families with children younger than 5 and the House Index, were associated with infection. Families with older than 13 were associated with a decreased frequency. After a month since the IC fever onset, the infection incidence was not influenced by exposure to an IC or vector density; it was influenced by the local seasonal behavior of dengue and the age. Additionally, we found asymptomatic infections accounted for 60% and a greater age was a protective factor for the presence of symptoms (RR 0.98; 95%CI 0.97-0.99). CONCLUSION: The evidence suggests that dengue endemic transmission in these locations is initially peridomestic, around an infected subject who may be asymptomatic due to demographic structure and endemicity, and it is influenced by other characteristics of the individual, the neighborhood and the location. Once the transmission chain has been established, dengue spreads in the community probably by the adults who, despite being the group with lower infection frequency, mostly suffer asymptomatic infections and have higher mobility. This scenario complicates the opportunity and the effectiveness of control programs and highlights the need to apply multiple measures for dengue control. PMID- 26671575 TI - Magnetoelectricity coupled exchange bias in BaMnF4. AB - Multiferroic BaMnF4 powder was prepared by hydrothermal method. Hysteretic field dependent magnetization curve at 5 K confirms the weak ferromagnetism aroused from the canted antiferromagnetic spins by magnetoelectric coupling. The blocking temperature of 65 K for exchange bias coincides well with the peak at 65 K in the zero-field cooled temperature-dependent magnetization curve, which has been assigned to the onset temperature of two-dimensional antiferromagnetism. An upturn kink of exchange field and coercivity with decreasing temperature was observed from 40 K to 20 K, which is consistent with the two-dimensional to three dimensional antiferromagnetic transition at Neel temperature (~26 K). In contrast to the conventional mechanism of magnetization pinned by interfacial exchange coupling in multiphases, the exchange bias in BaMnF4 is argued to be a bulk effect in single phase, due to the magnetization pinned by the polarization through magnetoelectric coupling. PMID- 26671574 TI - Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin. AB - Friedreich's Ataxia is a genetic disease caused by expansion of an intronic trinucleotide repeat in the frataxin (FXN) gene yielding diminished FXN expression and consequently disease. Since increasing FXN protein levels is desirable to ameliorate pathology, we explored the role of major cellular proteostasis pathways and mitochondrial proteases in FXN processing and turnover. We targeted p97/VCP, the ubiquitin proteasome pathway (UPP), and autophagy with chemical inhibitors in cell lines and patient-derived cells. p97 inhibition by DBeQ increased precursor FXN levels, while UPP and autophagic flux modulators had variable effects predominantly on intermediate FXN. Our data suggest that these pathways cannot be modulated to influence mature functional FXN levels. We also targeted known mitochondrial proteases by RNA interference and discovered a novel protease PITRM1 that regulates intermediate FXN levels. Treatment with the aforementioned chemical and genetic modulators did not have a differential effect in patient cells containing lower amounts of FXN. Interestingly, a number of treatments caused a change in total amount of FXN protein, without an effect on mature FXN. Our results imply that regulation of FXN protein levels is complex and that total amounts can be modulated chemically and genetically without altering the absolute amount of mature FXN protein. PMID- 26671577 TI - Neurosurgical Treatments for Patients with Chronic, Treatment-Refractory Depression: A Retrospective, Consecutive, Case Series Comparison of Anterior Capsulotomy, Anterior Cingulotomy and Vagus Nerve Stimulation. AB - BACKGROUND: The evidence base to guide therapeutic choices for patients with chronic and treatment-refractory depression (TRD) remains weak. There is limited comparative information available to guide the choice of intervention for patients with the most severe and disabling forms of illness. OBJECTIVES: The aim of this work was to describe the 12-month clinical outcomes of patients with chronic TRD treated with anterior capsulotomy (ACAPS; n = 5), anterior cingulotomy (ACING; n = 5) or vagus nerve stimulation (VNS; n = 5). METHODS: We performed a retrospective, consecutive, case series comparison. RESULTS: With clinical response defined as a >=50% reduction from the baseline MADRS score, response rates were 40% for ACAPS, 60% for ACING and 20% for VNS. Adverse effects from all three procedures were relatively mild, consistent with previous reports and, in most cases, transient. Adverse effects from VNS were related to active stimulation, and were modifiable and diminished in severity over time. There were no deaths. CONCLUSIONS: Although based on a small sample, our data represent a unique comparison of ACAPS, ACING and VNS for chronic TRD. The three cohorts were broadly equivalent in terms of baseline clinical characteristics, indices of chronicity, illness severity and estimates of previous failed treatments. ACING and ACAPS, but not VNS, were associated with favourable response rates at 12 months. PMID- 26671578 TI - Non-uniform Composition Profiles in Inorganic Thin Films from Aqueous Solutions. AB - A variety of metal oxide films (InGaOx, AlOx, "HafSOx") prepared from aqueous solutions were found to have non-uniform electron density profiles using X-ray reflectivity. The inhomogeneity in HafSOx films (Hf(OH)4-2x-2y(O2)x(SO4)y.zH2O), which are currently under investigation as inorganic resists, were studied in more detail by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and medium-energy ion scattering (MEIS). The HAADF-STEM images show a greater concentration of heavy atoms near the surface of a single layer film. MEIS data confirm the aggregation of Hf at the film surface. The denser "crust" layer in HafSOx films may directly impact patterning resolution. More generally, the phenomenon of surface-layer inhomogeneity in solution deposited films likely influences film properties and may have consequences in other thin-film systems under investigation as resists, dielectrics, and thin film transistor components. PMID- 26671576 TI - Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self Eating. AB - Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate. PMID- 26671579 TI - Clearance of Stone Fragments and Stone Dust by Continuous Flow Hydrodynamics in Percutaneous Renal Surgery: An In Vitro Study. AB - PURPOSE: To investigate the capacity of stone clearance in common percutaneous nephrolithotomy (PCNL) systems achieved solely by hydrodynamic effects in an in vitro setting. METHODS: A watertight cylindrical cast with a caliceal void served as an in vitro model. Various instruments for percutaneous renal surgery working with both continuous flow (fCF) and open Rutner sidearm (fCO) were tested. The model was loaded with standardized artificial stone material (2 mm in diameter) to examine stone removal by the vacuum cleaner effect and with sand (0.1-0.5 mm in diameter) to measure the washout effect caused by irrigation backflow. The association between washout of gravel and irrigation pressure was analyzed using ANOVA. Regression analysis was performed to assess the influence of the instruments' hydrodynamic characteristics-effective cross section of the outflow and irrigation flow volume. RESULTS: Provoking the vacuum cleaner effect removal of stones was only effective in fCF but not in fCO instruments. Depending on irrigation pressure, the volumetric flow rate and effective cross section of the outflow clearance of sand could be observed in various medium- and large-sized fCF and fCO instruments, whereas in small-sized systems, clearance effects were negligible. Regression analysis showed clearance of stone dust strongly associated with an instrument's volumetric flow rate. CONCLUSIONS: This in vitro study demonstrated that the application of medium- and large-sized fCF PCNL systems removes both "insignificant" stones and dust solely by hydrodynamic effects. Further studies have to show if these effects also occur in the in vivo situation. PMID- 26671580 TI - Influence of dendritic polyglycerol sulfates on knee osteoarthritis: an experimental study in the rat osteoarthritis model. AB - BACKGROUND: Anti-inflammatory nanoparticular compounds could represent a strategy to diminish osteoarthritis (OA) progression. The present study was undertaken to prove the uptake of nanoparticular dendritic polyglycerol sulfates (dPGS) by rat derived articular chondrocytes and to answer the question of whether dPGS could modulate knee joint cartilage degradation in a rat OA model and whether complications could arise. METHODS: dPGS uptake and cytotoxicity was assessed in cultured primary rat-derived articular chondrocytes. Subsequently, OA was induced in the right knee joints of 12 male Wistar rats by medial collateral ligament and meniscus transection. Unoperated left knees remained as controls. Six weeks post surgery six rats were either treated daily (14 days) with 30 mg/kg dPGS (s.c.) or a similar volume of physiological saline. Animals were analyzed clinically for gait alterations. Explanted knee joints were studied histologically using OA scores according to Mankin (1971), Glasson et al., (2010) and the synovitis score according to Krenn et al., (2006). Liver, spleen and kidneys were analyzed for degenerative changes due to dPGS accumulation. RESULTS: dPGS was taken up after 2 hours by the chondrocytes. Whereas no significant clinical signs of OA could be detected, at the histological level, all operated rat knee joints revealed features of OA in the medial compartment. The values produced by both OA score systems were lower in rats treated with dPGS compared with saline-treated animals. Synovitis score did not significantly differ between the groups. The analyzed organs revealed no degenerative changes. CONCLUSIONS: dPGS presented overall cyto- and biocompatibility, no accumulation in metabolizing organs and chondroprotective properties in the osteoarthritic knee joint. PMID- 26671581 TI - Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion. AB - INTRODUCTION: Papillary Glioneuronal Tumor (PGNT) is a grade I tumor which was classified as a separate entity in the World Health Organization Classification of the Central Nervous System 2007 in the group of mixed glioneuronal tumors. This tumor is rare and subclassifying PGNT represents a challenge. Recently, a fusion between SLC44A1 and PRKCA which encodes a protein kinase C involved in MAPK signaling pathway has been described in two studies (five cases). The current study aimed at raising the cytogenetic, histological and molecular profiles of PGNT and to determine if SLC44A1-PRKCA fusion represented a specific diagnostic marker to distinguish it from other glioneuronal tumors. RESULTS: We report on four pediatric cases of PGNT, along with clinico-radiologic and immunohistological features for which SLC44A1-PRKCA fusion assessment by fluorescence in situ hybridization, BRAF V600E and FGFR1 mutation by immunohistochemistry and direct DNA sequencing and KIAA1549-BRAF fusion by RT-PCR were performed. MAPK signaling pathway activation was investigated using phospho ERK immunohistochemistry and western blot. We analyzed fifteen cases of tumors with challenging histological or clinical differential diagnoses showing respectively a papillary architecture or periventricular location (PGNT mimics). fluorescence in situ hybridization analysis revealed a constant SLC44A1-PRKCA fusion signal in all PGNTs. None of PGNT mimics showed the SLC44A1-PRKCA fusion signal pattern. All PGNTs were negative for BRAF V600E and FGFR1 mutation, and KIAA1549-BRAF fusion. Phospho-ERK analysis provides arguments for the activation of the MAPK signaling pathway in these tumors. CONCLUSIONS: Here we confirmed and extended the molecular data on PGNT. These results suggest that PGNT belong to low grade glioma with MAPK signaling pathway deregulation. SLC44A1-PRKCA fusion seems to be a specific characteristic of PGNT with a high diagnostic value and detectable by FISH. PMID- 26671582 TI - Challenges facing the elimination of sleeping sickness in west and central Africa: sustainable control of animal trypanosomiasis as an indispensable approach to achieve the goal. AB - African trypanosomiases are infectious diseases caused by trypanosomes. African animal trypanosomiasis (AAT) remains an important threat for livestock production in some affected areas whereas human African trypanosomiasis (HAT) is targeted for elimination in 2020. In West and Central Africa, it has been shown that the parasites causing these diseases can coexist in the same tsetse fly or the same animal. In such complex settings, the control of these diseases must be put in the general context of trypanosomiasis control or "one health" concept where the coordination of control operations will be beneficial for both diseases. In this context, implementing control activities on AAT will help to sustain HAT control. It will also have a positive impact on animal health and economic development of the regions. The training of inhabitants on how to implement and sustain vector control tools will enable a long-term sustainability of control operations that will lead to the elimination of HAT and AAT. PMID- 26671583 TI - Obscure gastrointestinal bleeding and "obscure" capsule. May we switch on any lights? AB - CE soon became an effective tool in the pediatric age, where the invasiveness of conventional endoscopy always represented a real handicap. In this issue of our Journal an interesting consensus paper is reported under the leadership of F. Arguelles where a group of national CE experts shed light on its use in this population. PMID- 26671584 TI - Guideline for wireless capsule endoscopy in children and adolescents: A consensus document by the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition) and the SEPD (Spanish Society for Digestive Diseases). AB - INTRODUCTION: Capsule Endoscopy (CE) in children has limitations based mainly on age. The objective of this consensus was reviewing the scientific evidence. MATERIAL AND METHODS: Some experts from the Spanish Society of Gastroenterology (SEPD) and Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP) were invited to answer different issues about CE in children. These sections were: a) Indications, contraindications and limitations; b) efficacy of CE in different clinical scenarios; c) CE performance; d) CE-related complications; e) Patency Capsule; and f) colon capsule endoscopy. They reviewed relevant questions on each topic. RESULTS: The main indication is Crohn's disease (CD). There is no contraindication for the age and in the event that the patient not to swallow it, it should be administered under deep sedation with endoscopy and specific device. The CE is useful in CD, for the management of OGIB in children and in Peutz-Jeghers syndrome (in this indication has the most effectiveness). The main complication is retention, which should be specially taken into account in cases of CD already diagnosed with malnutrition. A preparation regimen based on a low volume of polyethylene glycol (PEG) the day before plus simethicone on the same day is the best one in terms of cleanliness although does not improve the results of the CE procedure. CONCLUSIONS: CE is safe and useful in children. Indications are similar to those of adults, the main one is CD to establish both a diagnosis and disease extension. Moreover, only few limitations are detected in children. PMID- 26671585 TI - Recurrence of liver metastases from colorectal cancer and repeat liver resection. AB - OBJECTIVE: The purpose of this study was to assess the resectability and effectiveness of repeat hepatectomy for relapsing liver metastases of colorectal origin in terms of morbidity, mortality, overall survival, and disease-free survival. METHODS: A retrospective study was performed on a prospective cohort of patients with colorectal liver metastases who underwent repeat surgery at Hospital Universitario San Cecilio, Granada (Spain), from March 2003 to June 2013. Primary outcome variables included survival and morbidity within 30 days post-surgery. RESULTS: A total of 147 patients with colorectal liver metastases underwent surgical excision during the study period; 61 patients had liver recurrence, and 34 of these received repeat surgery. The overall survival rate at 5 and 10 years for resected patients (n=27/34) was 48% and 48%. Mean hospital stay was 8.9 +/- 3.5 days, morbidity was 9%, and mortality was 0%. CONCLUSION: Repeat liver resection for colorectal liver metastases is a safe, effective surgical procedure whose results are similar to those obtained after initial liver resection. PMID- 26671586 TI - The diagnostic value of a globulin/platelet model for evaluating liver fibrosis in chronic hepatitis B patients. AB - BACKGROUND: Liver biopsy, which is considered the best method for evaluating hepatic fibrosis, has important adverse events. Therefore, non-invasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis B. AIM: To verify the usefulness of a new fibrosis index the globulin/platelet model in patients with chronic hepatitis B and to compare it with other noninvasive tests for predicting significant fibrosis. This study was the second to evaluate the globulin/platelet model in HBV patients. METHODS: We retrospectively investigated 228 patients with chronic hepatitis B who performed liver biopsy from 2013 to 2014. The globulin/platelet model, APGA [AST/Platelet/Gamma-glutamyl transpeptidase/Alfa-fetoprotein], FIB4, fibrosis index, cirrhosis discriminate score, and Fibro-quotient were calculated, and the diagnostic accuracies of all of the fibrosis indices were compared between the F0 2 (no-mild fibrosis) and F3-6 (significant fibrosis) groups. RESULTS: All of the noninvasive markers were significantly correlated with the stage of liver fibrosis (p < 0,001). To predict significant fibrosis (F >= 3), the area under the curve (95% CI) was found to be greatest for APGA (0.83 [0.74-0.86]), followed by FIB-4 (0.75[0.69-0.80]), the globulin/platelet model (0.74 [0.68-0.79]), fibrosis index (0.72 [0.6-0.78], cirrhosis discriminate score (0.71 [0.64-0.76]) and Fibro-quotient (0.62 [0.55-0.7]). The area under the receiver operating characteristic curves of APGA was significantly higher than that of the other noninvasive fibrosis markers (p < 0.05). CONCLUSIONS: While the APGA index was found to be the most valuable test for the prediction significant fibrosis in patients with chronic hepatitis B, GP model was the thirth valuable test. Therefore, we recommended that APGA could be used instead of the GP model for prediction liver fibrosis. PMID- 26671587 TI - Incidence, clinical outcomes, and therapeutic approaches of capsule endoscopy related adverse events in a large study population. AB - INTRODUCTION: Capsule endoscopy (CE) has become a first-line tool for small bowel (SB) examination. However, adverse events (AEs), such as CE retention or aspiration, may occur. The aims of this study were to evaluate incidence, clinical outcomes and therapeutic approaches of CE-related AEs in the largest series published to date. METHODS: Data from 5428 procedures performed at 12 institutions between August 2001 and January 2012 were retrospectively analyzed. Baseline patient characteristics; procedure; type, localization and symptoms before/after AEs; previous patency tests performed; therapeutic management and patient's outcome were recorded. RESULTS: The overall incidence of CE-related AEs was 1.9%: 2.0% for SB, 0.9% for esophageal and 0.5% for colon CE. The incidence of capsule retention was significantly higher than capsule aspiration (1.87% vs. 0.003%; p < 0.05), in patients suffering from inflammatory bowel disease (IBD) than in obscure GI bleeding (OGIB) (3.3% vs. 1.5%; p < 0.05) and in patients with the combination of nausea/vomiting, abdominal pain and distension. The SB was the most frequent localization of retention (88.2%). The use of patency tests -except for Patency(c) capsule- before CE was not a good predictor for AEs. Most of the patients with AEs developed no or mild symptoms (97%) and were managed by non surgical methods (64.4%). CONCLUSIONS: CE-related AEs are uncommon and difficult to predict by imagiological examinations. SB retention, that is usually asymptomatic, is the most frequent AE. In absence of symptoms, non-surgical management of CE-related AEs is recommended. PMID- 26671588 TI - What is the long-term outcome of a negative capsule endoscopy in patients with obscure gastrointestinal bleeding? AB - BACKGROUND AND AIMS: There are contradictory findings regarding long-term outcome in patients with obscure gastrointestinal bleeding and negative capsule endoscopy. Factors associated with rebleeding after a negative videocapsule are not entirely known. OBJECTIVE: The aim of this study was to compare the rebleeding rate between negative and positive capsule endoscopy patients and to identify predictive factors for rebleeding in patients with negative findings. MATERIAL AND METHODS: Consecutive patients with obscure gastrointestinal bleeding referred to a single center over a period of 5 years were identified. After exclusion of patients with a follow time < 6 months, 173 patients were included. Clinical information was retrospectively collected from medical records. Rebleeding was defined as evidence of melena/hematochezia, a drop in hemoglobin of >= 2 g/dL, or the need for transfusion 30 days after the index episode. RESULTS: The mean age was 61.7 years and 60% were female. The median follow up time was 27 months. Most patients were referred for occult gastrointestinal bleeding (67.1%) while 32.9% were referred for overt bleeding. More than 50% of the patients had negative capsule endoscopy. The rebleeding rate in negative capsule endoscopy is 16%, with a mean follow-up time of 25.8 months and is significantly lower than positive capsule endoscopy (16% vs. 30.2%, p = 0.02). Rebleeding after negative capsule endoscopy is higher in patients who need more transfusions of packet red blood cells before capsule endoscopy (3.0 vs. 0.9, p = 0.024) and have overt bleeding (46% vs. 13.9%, p = 0.03). In 53% of these patients, rebleeding occurs > 12 months after a negative capsule endoscopy. CONCLUSIONS: Patients with obscure gastrointestinal bleeding and a negative capsule endoscopy had a significantly lower rebleeding rate and can be safely followed. However, a higher transfusion of red blood cells previous to capsule endoscopy and an overt bleeding are associated with a higher rebleeding. So, it is reasonable to consider that these patients may benefit of at least one year of follow-up. PMID- 26671589 TI - Duodenal gastrointestinal stromal tumor and endoscopic ultrasound. AB - Duodenal gastrointestinal stromal tumors (GISTs) are a very rare condition. The pre-operative diagnosis can be a challenge but it is very important because GISTs have singularities that differ from other tumors and their location in the duodenum itself can have a major role in the choice of the surgical approach. We present two cases of duodenal GISTs where endoscopic ultrasound had a single role in their management, namely allowing the possibility to obtain material for immunocytochemical pre-operative diagnosis and regarding the precise relation to the papilla of Vater. The patients were operated and histological examination confirmed the diagnosis in both cases. PMID- 26671590 TI - Malignant degeneration of rectal endometriosis. AB - BACKGROUND: Endometriosis is a relatively common disease among women with child bearing potential, and rare before puberty or following menopause. It consists of the presence of hormone-responsive endometrium outside the endometrial cavity. CASE REPORT: We report the case of a patient with a rectal lesion, initially approached as a primary rectal malignancy, where histopathology eventually revealed an adenocarcinoma arising from endometrial tissue in the colonic wall. DISCUSSION: Endometriosis has an estimated rated of 10-20%. Sites may be split up into two larger categories - gonadal and extragonadal. The frequency of extragonadal endometriosis in the bowel is estimated to involve 3%-37% of women with pelvic endometriosis, and most lesions are found in the sigmoid colon and rectum. The malignant transformation of endometriotic lesions is estimated between 0.3% and 1% of cases. The gold standard in the diagnosis of intestinal endometriosis is exploratory laparotomy and the pathological study of specimens. Adjuvant radiotherapy and chemotherapy, although used for some patients, have not proven effective. PMID- 26671591 TI - Crohn's disease and Sweet's syndrome: A debut together. AB - The association of Sweet's syndrome and Crohn's disease is unusual, with less than 50 reported cases. We report a case in which these entities debut together. PMID- 26671592 TI - TIPS treatment in a patient with severe lower gastrointestinal bleeding with a misdiagnosis of cirrhotic portal hypertension. AB - Abernethy malformation is a rare abnormal embryological development of splanchnic venous system characterised by the presence of a congenital extrahepatic portosystemic shunt. We present a rare case of an adult male patient that was admitted with severe lower gastrointestinal bleeding, requiring multiple blood transfusions. The patient's medical history and the laboratory tests performed led to the misdiagnosis of a congenital Abernethy malformation. We present a rare case, discussing the reasons for the misdiagnosis and we conclude that management of clinical data and imaging are highly important to discard these types of congenital malformations that can mimic a portal hypertension condition. PMID- 26671593 TI - Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic. AB - Ciprofloxacin and amoxicillin/clavulanic are two widely used antibiotics due to their high efficacy and few side effects. While the percentage of hepatotoxicity of these antibiotics is low, their frequent use has led to a progressive increase in the number of cases. Both antibiotics have been associated with a wide variety of hepatotoxic reactions, from a slight rise of transaminases to fulminant hepatitis. Once hepatotoxicity secondary to a drug appears, the first step is to discontinue the drug. Physicians may opt to administer an alternative treatment with a different chemical structure. It should be borne in mind, however, that different chemical structures may also cause recurrent drug-induced liver injuries (DILI). We present the case of a patient who consecutively developed DILI due to ciprofloxacin and amoxicillin/clavulanic. PMID- 26671594 TI - Giant biloma as a result of a blunt abdominal trauma: A case report. AB - A 58-year-old man with a history of a heavy alcohol intake was admitted to hospital for a 3-weeks history of abdominal discomfort, nausea, vomiting and an increased abdominal girth that appeared progressively after an abdominal trauma due to an accidental fall. On physical examination, jaundice was present and the abdomen was distended with no tenderness on palpation. Laboratory studies showed an increased white-cell count, an elevated C-reactive protein and abnormal liver function tests. Abdominal ultrasonography showed a large fluid collection in the right side of the abdomen. An abdominal computed tomography scan revealed a gallbladder perforation communicating to a big subcapsular hepatic biloma of 9.5 by 25.0 by 35.0 centimeters, which was compressing the liver and other intraabdominal organs. Finally, our patient underwent an open cholecystectomy with drainage of the biloma, and a partial resection of the Glisson's capsule. Macroscopic and microscopic examination of the resected specimens confirmed the diagnosis of traumatic gallbladder perforation. Gallbladder traumatic injury is a rare entity. The diagnosis represents a challenge because of its low incidence, its association with other lesions of vital organs and the nonspecific and insidious symptoms that can produce. Treatment depends on the type and severity of the damage caused; nevertheless, cholecystectomy remains the treatment of choice in patients with rupture or avulsion of the gallbladder. To our knowledge, this is the first report in the English literature of an isolated blunt traumatic gallbladder injury that was associated with the development of a large biloma. PMID- 26671595 TI - t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders. AB - Through a combined approach integrating RNA-Seq, SNP-array, FISH and PCR techniques, we identified two novel t(15;21) translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12. One is a complex t(15;21)(q24;q22), with both breakpoints mapped at the nucleotide level, joining RUNX1 to SIN3A and UBL7-AS1 in a patient with myelodysplasia. The other is a recurrent t(15;21)(q21;q22), juxtaposing RUNX1 and TCF12, with an opposite transcriptional orientation, in three myeloid leukemia cases. Since our transcriptome analysis indicated a significant number of differentially expressed genes associated with both translocations, we speculate an important pathogenetic role for these alterations involving RUNX1. PMID- 26671596 TI - Doctor gets suspended prison sentence for not giving priority to "very sick boy". PMID- 26671597 TI - Phosphatidylethanol (PEth) in blood samples from "driving under the influence" cases as indicator for prolonged excessive alcohol consumption. AB - Phosphatidylethanol (PEth) is considered as specific biomarker of alcohol consumption. Due to accumulation after repeated drinking, PEth is suitable to monitor long-term drinking behavior. To examine the applicability of PEth in "driving under the influence of alcohol" cases, 142 blood samples with blood alcohol concentrations (BAC) ranging from 0.0-3.120/00 were analyzed for the presence of PEth homologues 16:0/18:1 (889 +/- 878 ng/mL; range = 1.60/00 and in 31.6% of the samples with a BAC < 1.60/00. Similar results were obtained for PEth 16:0/18:2 with a threshold of 300 ng/mL. Both criteria, PEth 16:0/18:1 and PEth 16:0/18:2, were conform in the evaluation of drinking habits in 88.7% of blood samples. These results show the possibility to detect prolonged excessive alcohol consumption, even if the BAC is below the legal threshold of 1.60/00 for driving aptitude assessment. As a consequence, concentrations of PEth 16:0/18:1 >= 700 ng/mL and of PEth 16:0/18:2 >= 300 ng/mL may be considered as indicators for the necessity of driving aptitude assessment in addition to BAC. PMID- 26671598 TI - Frequency of skeletal-related events and associated healthcare resource use and costs in US patients with multiple myeloma. AB - OBJECTIVE: A potential complication for all new multiple myeloma (MM) patients is the clinical presentation of osteolytic lesions which increase the risk for skeletal-related events (SREs). However, the contribution of SREs to the overall economic impact of MM is unclear. The impact of SREs on healthcare resource utilization (HCRU) and costs for US patients with MM was analyzed in Truven Health Marketscan Commercial Claims and Medicare Supplemental Databases. METHODS: Adults diagnosed with MM between January 1, 2005 and December 31, 2010 with >=2 claims >=30 days apart (first claim = index date) were included. SREs included: hypercalcemia, pathologic fracture, surgery for the prevention and treatment of pathologic fractures or spinal cord compression, and radiation for bone pain. Rates of HCRU (outpatient [OP], inpatient [IP], emergency room [ER], orthopedic consultation [OC], and ancillary) and healthcare costs were compared between MM patients with and without SREs. Inverse propensity weighting was applied to adjust for potential bias. RESULTS: Of 1028 MM patients (mean age = 67, standard deviation = 13.2), 596 patients with >=1 SRE and 432 without SREs were assessed. HCRU rates in IP, ER, and ancillary (p < 0.01) and mean total costs of OP, IP, and ER were significantly higher (p < 0.05) for patients with vs without SREs during follow-up. HCRU rates also increased with SRE frequency (p < 0.05 in OP, IP, ER, OC, and ancillary), as did mean total healthcare costs, except for OC (p < 0.001). LIMITATIONS: A broad assessment of pharmacotherapy for the treatment of MM was not an objective of the current study. Bisphosphonate use was evaluated; however, results were descriptively focused on frequency of utilization only and were not included in the broader cost and HCRU analysis. CONCLUSIONS: Among US patients with MM, higher SRE frequency was associated with a significant trend of higher HCRU and total healthcare costs in several settings. PMID- 26671602 TI - The impact of concussion on cardiac autonomic function: A systematic review. AB - PRIMARY OBJECTIVE: To evaluate the evidence regarding the effect of concussion on cardiac autonomic function (CAF). INCLUSION CRITERIA: Original research; available in English; included participants with concussion or mild traumatic brain injury (mTBI) and a comparison group; included measures of heart rate (HR) and/or heart rate variability (HRV) as outcomes. Studies of humans (greater than 6 years old) and animals were included. Critical appraisal tools: The Downs and Black (DB) criteria and Structured Effectiveness Quality Evaluation Scale (SEQES). RESULTS: Nine full-length articles and four abstracts were identified. There is conflicting evidence regarding CAF at rest following concussion. There is evidence of elevated HR and reduced HRV with low-intensity, steady-state exercise up to 10 days following concussion. There was no significant difference in HRV during isometric handgrip testing or HR while performing cognitive tasks following concussion. The validity of current literature is limited by small sample sizes, lack of female or paediatric participants, methodological heterogeneity and lack of follow-up. CONCLUSIONS: While there is some evidence to suggest CAF is altered during physical activity following concussion, methodological limitations highlight the need for further research. Understanding the effect of concussion on CAF will contribute to the development of more comprehensive concussion management strategies. PMID- 26671603 TI - Acidophilic actinobacteria synthesised silver nanoparticles showed remarkable activity against fungi-causing superficial mycoses in humans. AB - Superficial mycoses are limited to the most external part of the skin and hair and caused by Malassezia sp., Trichophyton sp. and Candida sp. We report extracellular biosynthesis of silver nanoparticles (AgNPs) by acidophilic actinobacteria (SF23, C9) and its in vitro antifungal activity against fungi causing superficial mycoses. The phylogenetic analysis based on the 16S rRNA gene sequence of strains SF23 and C9 showed that they are most closely related to Pilimelia columellifera subsp. pallida GU269552(T). The detection of AgNPs was confirmed by visual observation of colour changes from colourless to brown, and UV-vis spectrophotometer analysis, which showed peaks at 432 and 427 nm, respectively. These AgNPs were further characterised by nanoparticle tracking analysis (NTA), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The FTIR analysis exhibited the presence of proteins as capping agents. The TEM analysis revealed the formation of spherical and polydispersed nanoparticles in the size range of 4-36 nm and 8 60 nm, respectively. The biosynthesised AgNPs were screened against fungi-causing superficial mycoses viz., Malassezia furfur, Trichophyton rubrum, Candida albicans and C. tropicalis. The highest antifungal activity of AgNPs from SF23 and C9 against T. rubrum and the least against M. furfur and C. albicans was observed as compared to other tested fungi. The biosynthesised AgNPs were found to be potential anti-antifungal agent against fungi-causing superficial mycoses. PMID- 26671606 TI - Occurrence of persistent organic pollutants in sediments and biota from Portugal versus European incidence: A critical overview. AB - Persistent organic pollutants (POPs) are widespread compounds, such as organohalogenated compounds, polycyclic aromatic hydrocarbons (PAHs) and pesticides, which can be found in all types of environmental compartments. Their presence in the aquatic environment is a worldwide problem, with emphasis on sediments which act as depository and consequently as a source of hydrophobic, recalcitrant and harmful compounds. Besides, these pollutants might affect the reproduction and mortality of living organisms, diverging in their potential to bioaccumulate in tissues. The present paper aims to review the occurrence of POPs in sediments and biota from the coastal, estuarine and river areas of Portugal. The list of the studied compounds comprises organohalogenated compounds, PAHs, organometallic compounds, pesticides, sterols, fatty acids and pharmaceutical compounds. The contamination of sediments by various pollutants is presented, such as PAHs up to 7,350 ng g(-1) found in Sado estuary and polychlorinated biphenyls up to 62.2 ng g(-1) in the case of sediments collected in Ria de Aveiro. The occurrence of these persistent toxic substances in sediments demonstrates aquatic contamination from agricultural, industrial and urban discharges and the concern about the potential risks to aquatic organisms, wildlife and humans. In fact, several classes of POPs have also been found in biota, such as polychlorinated biphenyls up to 810.9 ng g(-1) in sentinel fish from the Douro River estuary and pesticides in bivalves from the Sado River estuary. The importance of further systematic research on sediments and biota is here highlighted to compare the contamination of these two reservoirs; to assess their spatial and temporal variation; and to determine other classes of POPs that were not investigated yet (e.g., industrial compounds, estrogens and many classes of pharmaceuticals). PMID- 26671607 TI - Lateral access of arcuate ligament in Whipple procedure with video. PMID- 26671608 TI - Direct E-jet printing of three-dimensional fibrous scaffold for tendon tissue engineering. AB - Tissue engineering (TE) offers a promising strategy to restore diseased tendon tissue. However, a suitable scaffold for tendon TE has not been achieved with current fabrication techniques. Herein, we report the development of a novel electrohydrodynamic jet printing (E-jetting) for engineering 3D tendon scaffold with high porosity and orientated micrometer-size fibers. The E-jetted scaffold comprised tubular multilayered micrometer-size fibrous bundles, with interconnected spacing and geometric anisotropy along the longitudinal direction of the scaffold. Fiber diameter, stacking pattern, and interfiber distance have been observed to affect the structural stability of the scaffold, of which the enhanced mechanical strength can be obtained for scaffolds with thick fibers as the supporting layer. Human tenocytes showed a significant increase in cellular metabolism on the E-jetted scaffolds as compared to that on conventional electrospun scaffolds (2.7-, 2.8-, and 3.1-fold increase for 150, 300, and 600 um interfiber distance, respectively; p < 0.05). Furthermore, the scaffolds provided structural support for human tenocytes to align with controlled orientation along the longitudinal direction of the scaffold, and promoted the expression of collagen type I. For the first time, E-jetting has been explored as a novel scaffolding approach for tendon TE, and offers a 3D fibrous scaffold to promote organized tissue reconstruction for potential tendon healing. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 616-627, 2017. PMID- 26671609 TI - DANIO-CODE: Toward an Encyclopedia of DNA Elements in Zebrafish. AB - The zebrafish has emerged as a model organism for genomics studies. The symposium "Toward an encyclopedia of DNA elements in zebrafish" held in London in December 2014, was coorganized by Ferenc Muller and Fiona Wardle. This meeting is a follow up of a similar previous workshop held 2 years earlier and represents a push toward the formalization of a community effort to annotate functional elements in the zebrafish genome. The meeting brought together zebrafish researchers, bioinformaticians, as well as members of established consortia, to exchange scientific findings and experience, as well as to discuss the initial steps toward the formation of a DANIO-CODE consortium. In this study, we provide the latest updates on the current progress of the consortium's efforts, opening up a broad invitation to researchers to join in and contribute to DANIO-CODE. PMID- 26671610 TI - On-chip cell lysis by antibacterial non-leaching reusable quaternary ammonium monolithic column. AB - Reusable antibacterial non-leaching monolithic columns polymerized in microfluidic channels designed for on-chip cell lysis applications were obtained by the photoinitiated free radical copolymerization of diallyldimethylammonium chloride (DADMAC) and ethylene glycol diacrylate (EGDA) in the presence of a porogenic solvent. The microfluidic channels were fabricated in cross-linked poly(methyl methacrylate) (X-PMMA) substrates by laser micromachining. The monolithic columns have the ability to inhibit the growth of, kill and efficiently lyse Gram-positive Micrococcus luteus (Schroeter) (ATCC 4698) and Kocuria rosea (ATCC 186), and Gram-negative bacteria Pseudomonas putida (ATCC 12633) and Escherichia coli (ATCC 35218) by mechanically shearing the bacterial membrane when forcing the cells to pass through the narrow pores of the monolithic column, and simultaneously disintegrating the cell membrane by physical contact with the antibacterial surface of the column. Cell lysis was confirmed by off-chip PCR without the need for further purification. The influence of the cross-linking monomer on bacterial growth inhibition, leaching, lysis efficiency of the monolithic column and its mechanical stability within the microfluidic channel were investigated and analyzed for three different cross linking monomers: ethylene glycol dimethacrylate (EGDA), ethylene glycol dimethacrylate (EGDMA) and 1,6-hexanediol dimethacrylate (1,6-HDDMA). Furthermore, the bonding efficiency of two X-PMMA substrates with different cross linking levels was studied. The monolithic columns were shown to be stable, non leaching, and reusable for over 30 lysis cycles without significant performance degradation or DNA carryover when they were back-flushed between lysis cycles. PMID- 26671611 TI - Rotary ATPases: A New Twist to an Ancient Machine. AB - Rotary ATPases are energy-converting nanomachines found in the membranes of all living organisms. The mechanism by which proton translocation through the membrane drives ATP synthesis, or how ATP hydrolysis generates a transmembrane proton gradient, has been unresolved for decades because the structure of a critical subunit in the membrane was unknown. Electron cryomicroscopy (cryoEM) studies of two rotary ATPases have now revealed a hairpin of long, horizontal, membrane-intrinsic alpha-helices in the a-subunit next to the c-ring rotor. The horizontal helices create a pair of aqueous half-channels in the membrane that provide access to the proton-binding sites in the rotor ring. These recent findings help to explain the highly conserved mechanism of ion translocation by rotary ATPases. PMID- 26671612 TI - Microfluidic Investigation of Nanoparticles' Role in Mobilizing Trapped Oil Droplets in Porous Media. AB - The flow of multiple fluid phases in porous media often results in trapped droplets of the nonwetting phase. Recent experimental and theoretical studies have suggested that nanoparticle aqueous dispersions may be effective at mobilizing trapped droplets of nonwetting fluid (oil) in porous media. Hypotheses to explain the observation include the nanoparticles' modification of solid wettability, droplet stabilization, and changes in interfacial tension and interface rheology. However, because it is difficult to observe droplet behavior on the pore scale, how those factors contribute to oil droplet mobilization has not been fully understood. In this work, we investigated the nanoparticles' role in nanoparticle-based improved recovery of the nonwetting phase through the direct observation of the mobilization of trapped oil droplets in microfluidic structures that mimic pore-throat geometries. A microfluidic platform was constructed for this study, on which different displacing liquids including aqueous surfactant solutions and nanoparticle suspensions were tested. We found that the nanoparticle concentration is positively related to the oil mobilization efficiency. An approximate mathematical model for calculating the maximum size of an oil droplet trapped in a pore-throat geometry for a fixed flow rate matches the experiment result for displacing liquid with no nanoparticles. The model still holds when the nanoparticle suspension is a displacing liquid. We concluded that nanoparticles mobilize oil in these geometries in a mechanism similar to that for surfactants, which is an increase in capillary number rather than an effect of other fluidic or interfacial properties such as the dynamics adsorption of nanoparticle or dilational rheology of a nanoparticle-adsorbed interface. PMID- 26671613 TI - [Morphologic and tomodensitometric comparative analysis of two cyclotocephalic newborns]. AB - Two specimens of cyclotocephalic newborns, coming from museum collections, have been the subject of a comparative morphologic analysis. This one comprised an external examination and a CT scan exploration. If the craniofacial features were similar, one had a quasi-normal brain, while the second specimen displayed alobar holoprosencephaly. This observation relatively surprising is discussed in the light of current knowledge on the developmental genetics of this family of malformations. PMID- 26671614 TI - A novel zinc(ii) metal-organic framework with a diamond-like structure: synthesis, study of thermal robustness and gas adsorption properties. AB - A solvothermal reaction of Zn(ii) salt with methanetetrabenzoic acid (H4MTB) and 1,4,8,11-tetraazacyclotetradecane (cyclam, CYC) created a new microporous metal organic framework {[Zn2(MU4-MTB)(kappa(4)-CYC)2].2DMF.7H2O}n (DMF = N,N' dimethylformamide). Single crystal X-ray diffraction showed that the complex exhibits a four-fold interpenetrated diamond-like structure topology with 1D jar like channels with sizes about 14.1 * 14.1 and 2.4 * 2.4 A(2). The stability of the framework and activation conditions of the compound have been studied by high energy powder X-ray diffraction during in situ heating, thermogravimetric analysis coupled with mass spectrometry and infrared spectroscopy performed at different temperatures. The gas adsorption behaviour of {[Zn2(MU4-MTB)(kappa(4) CYC)2].2DMF.7H2O}n was studied by adsorption of Ar, N2, CO2 and H2. Nitrogen and argon adsorption showed that the activated sample exhibits Brunauer-Emmet-Teller (BET) specific surface areas of 644 m(2) g(-1) (N2) and 562 m(2) g(-1) (Ar). The complex adsorbs carbon dioxide with a maximum storage capacity of 10.5 wt% at 273 K and 101 kPa. The observed hydrogen uptake was 1.27 wt% at 77 K and 800 Torr, which is the highest value reported for the compounds containing a MTB(4-) linker. The adsorption heats of carbon dioxide and hydrogen, calculated according to the Clausius-Clapeyron equation, were in the range 22.8-22.4 kJ mol(-1) for CO2 and 8.9-3.2 kJ mol(-1) for H2, indicating weak interactions of the gases with the framework. PMID- 26671615 TI - Highly efficient and easy protease-mediated protein purification. AB - As both research on and application of proteins are rarely focused on the resistance towards nonspecific proteases, this property remained widely unnoticed, in particular in terms of protein purification and related fields. In the present study, diverse aspects of protease-mediated protein purification (PMPP) were explored on the basis of the complementary proteases trypsin and proteinase K as well as the model proteins green fluorescent protein (GFP) from Aequorea victoria, lipase A from Candida antarctica (CAL-A), a transaminase from Aspergillus fumigatus (AspFum), quorum quenching lactonase AiiA from Bacillus sp., and an alanine dehydrogenase from Thermus thermophilus (AlaDH). While GFP and AiiA were already known to be protease resistant, the thermostable enzymes CAL-A, AspFum, and AlaDH were selected due to the documented correlation between thermostability and protease resistance. As proof of principle for PMPP, recombinant GFP remained unaffected whereas most Escherichia coli (E. coli) host proteins were degraded by trypsin. PMPP was highly advantageous compared to the widely used heat-mediated purification of commercial CAL-A. The resistance of AspFum towards trypsin was improved by rational protein design introducing point mutation R20Q. Trypsin also served as economical and efficient substitute for site-specific endopeptidases for the removal of a His-tag fused to AiiA. Moreover, proteolysis of host enzymes with interfering properties led to a strongly improved sensitivity and accuracy of the NADH assay in E. coli cell lysate for AlaDH activity measurements. Thus, PMPP is an attractive alternative to common protein purification methods and facilitates also enzyme characterization in cell lysate. PMID- 26671616 TI - Bioprospecting and evolving alternative xylose and arabinose pathway enzymes for use in Saccharomyces cerevisiae. AB - Bioprospecting is an effective way to find novel enzymes from strains with desirable phenotypes. Such bioprospecting has enabled organisms such as Saccharomyces cerevisiae to utilize nonnative pentose sugars. Yet, the efficiency of this pentose catabolism (especially for the case of arabinose) remains suboptimal. Thus, further pathway optimization or identification of novel, optimal pathways is needed. Previously, we identified a novel set of xylan catabolic pathway enzymes from a superior pentose-utilizing strain of Ustilago bevomyces. These enzymes were used to successfully engineer a xylan-utilizing S. cerevisiae through a blended approach of bioprospecting and evolutionary engineering. Here, we expanded this approach to xylose and arabinose catabolic pathway engineering and demonstrated that bioprospected xylose and arabinose catabolic pathways from U. bevomyces offer alternative choices for enabling efficient pentose catabolism in S. cerevisiae. By introducing a novel set of xylose catabolic genes from U. bevomyces, growth rates were improved up to 85 % over a set of traditional Scheffersomyces stipitis pathway genes. In addition, we suggested an alternative arabinose catabolic pathway which, after directed evolution and pathway engineering, enabled S. cerevisiae to grow on arabinose as a sole carbon source in minimal medium with growth rates upwards of 0.05 h(-1). This pathway represents the most efficient growth of yeast on pure arabinose minimal medium. These pathways provide great starting points for further strain development and demonstrate the utility of bioprospecting from U. bevomyces. PMID- 26671617 TI - Indoleamine-2,3-Dioxygenase/Kynurenine Pathway as a Potential Pharmacological Target to Treat Depression Associated with Diabetes. AB - Diabetes is a chronic disease associated with depression whose pathophysiological mechanisms that associate these conditions are not fully elucidated. However, the activation of the indoleamine-2,3-dioxygenase (IDO), an enzyme that participate of the tryptophan metabolism leading to a decrease of serotonin (5-HT) levels and whose expression is associated with an immune system activation, has been proposed as a common mechanism that links depression and diabetes. To test this hypothesis, diabetic (DBT) and normoglycemic (NGL) groups had the cytokines (TNFalpha, IL-1beta, and IL-6) and 5-HT and norepinephrine (NE) levels in the hippocampus (HIP) evaluated. Moreover, the effect of the selective serotonin reuptake inhibitor fluoxetine (FLX), IDO direct inhibitor 1-methyl-tryptophan (1 MT), anti-inflammatory and IDO indirect inhibitor minocycline (MINO), or non selective cyclooxygenase inhibitor ibuprofen (IBU) was evaluated in DBT rats submitted to the modified forced swimming test (MFST). After the behavioral test, the HIP was obtained for IDO expression by Western blotting analysis. DBT rats exhibited a significant increase in HIP levels of TNFalpha, IL-1beta, and IL-6 and a decrease in HIP 5-HT and NA levels. They also presented a depressive-like behavior which was reverted by all employed treatments. Interestingly, treatment with MINO, IBU, or FLX but not with 1-MT reduced the increased IDO expression in the HIP from DBT animals. Taken together, our data support our hypothesis that neuroinflammation in the HIP followed by IDO activation with a consequent decrease in the 5-HT levels can be a possible pathophysiological mechanism that links depression to diabetes. PMID- 26671618 TI - Traumatic Brain Injury Increases the Expression of Nos1, Abeta Clearance, and Epileptogenesis in APP/PS1 Mouse Model of Alzheimer's Disease. AB - To test the hypothesis that an amyloidogenic genetic background predisposes to worsening of post-TBI outcome, we investigated whether traumatic brain injury (TBI) in amyloid precursor protein (APP)/PS1 mice aggravates epileptogenesis and/or enhances somatomotor and cognitive impairment. To elaborate the mechanisms of worsening outcomes, we studied changes in the expression of genes involved in APP processing and Tau pathways in the perilesional cortex, ipsilateral thalamus, and ipsilateral hippocampus 16 weeks post-TBI. Mild (mTBI) or severe TBI (sTBI) was triggered using controlled cortical impact in 3-month-old APP/PS1 mice and wild-type (Wt) littermates. Morris water-maze revealed a genotype effect on spatial learning and memory as APP/PS1-sTBI mice performed more poorly than Wt sTBI mice (p < 0.05). Epileptogenesis was affected by genotype and TBI as 88 % of APP/PS1-sTBI mice had epilepsy compared to 11 % in Wt-sTBI (genotype effect p < 0.01) or 50 % in APP/PS1-sham groups (TBI effect p < 0.05). The higher the seizure frequency, the higher the cortical expression of Nos1 (r = 0.83, p < 0.001) and Mapk3 (r = 0.67, p < 0.001). Immunohistochemical analysis confirmed increased amount of NOS1 protein in neuronal somata and processes in the perilesional cortex in APP/PS1-sTBI mice compared to APP/PS1-sham (p < 0.05) or Wt-sTBI mice (p < 0.01). Motor impairment correlated (p < 0.001) with the increased cortical expression of genes encoding proteins related to beta-amyloid (Abeta) clearance, including Clu (r = 0.83), Abca1 (r = 0.78), A2m (r = 0.76), Apoe (r = 0.70), and Ctsd (r = 0.63). Immunohistochemical analysis revealed a focal reduction in Abeta load lateral to lesion core in APP/PS1-sTBI mice compared to APP/PS1-sham mice (p < 0.05). The present study provides the first comprehensive evidence of exacerbated epileptogenesis and its molecular mechanisms in Alzheimer's disease (AD)-related genetic background after TBI. PMID- 26671620 TI - Heart Rate-Dependent Hysteresis of T-Wave Alternans in Primary Prevention ICD Patients. AB - BACKGROUND: T-wave alternans (TWA) is usually performed at accelerated heart rates (HR) during exercise, while recovery TWA is typically not analyzed. Consequently, it is still unknown if TWA shows a HR-dependent hysteresis or not. Thus, the aim of the present study was to investigate TWA dependency on HR during both the exercise and recovery phases of an ergometer test, and to evaluate if recovery TWA may contribute to identify subjects at increased risk of arrhythmic events. METHODS: Our HR adaptive match filter was used to identify TWA from electrocardiographic recordings acquired during a bicycle ergometer test in 266 patients with implanted cardio-defibrillator. During the 4-year follow-up, 76 patients developed tachycardia or ventricular fibrillation (ICD_Cases) and 190 did not (ICD_Controls). RESULTS: TWA was statistically lower during exercise than recovery for HRs between 75 and 110 bpm (16-21 MUV vs 20-27 MUV; P < 0.05), and reverse for HRs between 120 and 130 bpm (41-51 MUV vs 28 MUV; P < 0.05). ICD_Cases and ICD_Controls showed significantly different TWA at 80 bpm (20 MUV vs 15 MUV; P < 0.05) and 140 bpm (15 MUV vs 22 MUV; P < 0.05) during exercise, and at 90 bpm (38 MUV vs 21 MUV; P < 0.05) and 95 bpm (33-24 MUV vs 28 MUV; P < 0.05) during recovery. CONCLUSIONS: TWA shows a HR-dependent hysteresis and there is a different behavior of TWA in ICD_Cases and ICD_Controls groups. Consequently, beside exercise TWA also recovery TWA may contribute to identify subjects at increased risk of arrhythmic events. PMID- 26671621 TI - Alexithymia in Uraemic Pruritus. PMID- 26671619 TI - GSK-3beta inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/beta-catenin signaling pathway after acute ischemic stroke in rats. AB - Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3beta (GSK-3beta), to evaluate the role of the Wnt/beta-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of beta-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3beta. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/beta-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke. PMID- 26671622 TI - The Use of Bandage Contact Lenses in Adenoviral Keratoconjunctivitis. AB - PURPOSE: To evaluate the safety and efficacy of the use of the bandage contact lenses (BCLs) in adenoviral keratoconjunctivitis-related ocular surface problems. METHODS: Fifteen eyes of 15 consecutive patients presenting at the Ankara University Medical Center, Cornea and Contact Lens Service, and requiring BCL use for adenoviral keratoconjunctivitis-related ocular surface problems were enrolled. Visual acuity, slitlamp examination findings, indication and duration of the BCL use, the total follow-up, and any adjuvant medication were recorded. All patients were followed regarding the success of treatment and adverse effects associated with BCL use. RESULTS: The average age at the time of presentation was 26.8+/-15.5 years. The major reasons for BCL use included epithelial defect (7 eyes), filamentous keratopathy (5 eyes), epithelial edema (1 eyes), and filamentous keratopathy together with epithelial defect (2 eyes). After the first appearance of conjunctivitis symptoms, the mean time to BCL application was 9.0+/ 3.9 days. The mean duration of contact lens wear was 9.9+/-6.5 days, and the mean follow-up was 26.4+/-15.8 days. Preservative-free artificial tears and topical antibiotics were used in all cases. Besides, topical ganciclovir 0.15% gel (8 eyes), topical 0.4% povidone-iodine solution (9 eyes), and topical steroids (11 eyes) were used in various combinations. At the end of the follow-up period, the mean visual acuity improved from 0.23+/-0.32 logMAR units (~0.6 Snellen line) to 0.0l+/-0.04 logMAR units (~1.0 Snellen line) (P=0.042). No sight-threatening complication related to contact lens wear was encountered. CONCLUSION: Adjuvant use of BCLs seems to be safe and effective in the treatment of adenoviral keratoconjunctivitis-related ocular surface problems. Close follow-up and prophylactic use of topical antibiotics are rationalistic for prevention of secondary infections. PMID- 26671623 TI - Surgical techniques to prevent reflux esophagitis in proximal gastrectomy reconstructed by esophagogastrostomy with preservation of the lower esophageal sphincter, pyloric and celiac branches of the vagal nerve, and reconstruction of the new His angle for early proximal gastric cancer. AB - PURPOSE: This article describes the surgical techniques to prevent reflux esophagitis (RE) after proximal gastrectomy reconstructed by esophagogastrostomy (PGE) preservation of the lower esophageal sphincter (LES) and both pyloric and celiac branches of the vagal nerve (PCVN), and reconstruction of the new His angle (HA) for early proximal gastric cancer (PGC). METHODS: Twenty patients after PGE were divided into 2 groups (group A: 10 patients without preserved LES and PCVN for advanced PGC; group B: 10 patients with preserved LES and PCNV and the addition of a new HA for early PGC). A postoperative interview on gastroesophageal reflux disease (GERD) and satisfaction with this procedure and the collection of endoscopic findings for RE and stasis of the remnant stomach (SRS) were conducted 1 year after PGE in groups A and B. RESULTS: The rates of proton pump inhibitor administration and the symptoms of GERD, RE and SRS in group A were significantly higher than those in group B (p = 0.0433, p = 0.0190, p = 0.0253, p = 0.0190, respectively). Seven out of 10 patients in group A voiced dissatisfaction. Patients in group B were significantly more satisfied with this procedure than those in group A (p = 0.0010). CONCLUSION: This method is useful for preventing postoperative GERD including RE in early PGC patients. PMID- 26671624 TI - Psychiatric Consultations in Less-Than-Private Places: Challenges and Unexpected Benefits of Hospital Roommates. PMID- 26671625 TI - Do people with borderline personality disorder complicated by antisocial personality disorder benefit from the STEPPS treatment program? AB - Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a group treatment for persons with borderline personality disorder (BPD). We describe results from two data sets on outcome in persons who participated in STEPPS with BPD alone or BPD plus antisocial personality disorder (ASPD). In Study 1, we examined the effect of comorbid ASPD on outcome in 65 persons with BPD who participated in a randomized controlled trial at an academic medical centre. In Study 2, we examined the effect of comorbid ASPD on outcome in 64 offenders with BPD who participated in STEPPS in correctional settings. All subjects were assessed for the presence of BPD and ASPD. In Study 1, subjects with ASPD experienced greater improvement in BPD symptoms, impulsiveness and global symptoms. In Study 2, offenders with ASPD experienced greater improvement in positive and negative behaviours and positive affectivity. We conclude that persons with BPD plus ASPD benefit from STEPPS in community and correctional settings. The findings suggest that persons with BPD plus ASPD show greater improvement in some domains than persons with BPD only. People with ASPD should not be automatically excluded from participation in the program. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26671627 TI - Multilocus phylogeography reveals nested endemism in a gecko across the monsoonal tropics of Australia. AB - Multilocus phylogeography can uncover taxonomically unrecognized lineage diversity across complex biomes. The Australian monsoonal tropics include vast, ecologically intact savanna-woodland plains interspersed with ancient sandstone uplands. Although recognized in general for its high species richness and endemism, the biodiversity of the region remains underexplored due to its remoteness. This is despite a high rate of ongoing species discovery, especially in wetter regions and for rock-restricted taxa. To provide a baseline for ongoing comparative analyses, we tested for phylogeographic structure in an ecologically generalized and widespread taxon, the gecko Heteronotia binoei. We apply coalescent analyses to multilocus sequence data (mitochondrial DNA and eight nuclear DNA introns) from individuals sampled extensively and at fine scale across the region. The results demonstrate surprisingly deep and geographically nested lineage diversity. Several intra-specific clades previously shown to be endemic to the region were themselves found to contain multiple, short-range lineages. To infer landscapes with concentrations of unique phylogeographic diversity, we probabilistically estimate the ranges of lineages from point data and then, combining these estimates with the nDNA species tree, estimate phyloendemism across the region. Highest levels of phyloendemism occur in northern Top End, especially on islands, across the topographically complex Arnhem escarpment, and across the sandstone ranges of the western Gulf region. These results drive home that deep phylogeographic structure is prevalent in tropical low-dispersal taxa, even ones that are ubiquitous across geography and habitats. PMID- 26671626 TI - Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer. AB - BACKGROUND: Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. METHODS: In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARbeta (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56 0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24 6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). DISCUSSION: PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE 1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence. PMID- 26671629 TI - Does Simulation-Based Training Improve Procedural Skills of Beginners in Interventional Cardiology?--A Stratified Randomized Study. AB - OBJECTIVE: To assess whether mentored simulation-based-training can improve the procedural skills of beginners in coronary interventional procedures. BACKGROUND: Simulation based-catheter training is a valuable tool to practice interventional procedures. Whether this type of training enhances the procedural skills of fellows learning percutaneous coronary interventions has never been studied. METHODS: Eighteen cardiology fellows were randomized either into the simulation based training (n = 9) or the control group (n = 9). The simulation group received 7.5 hours of virtual reality (VR) simulation training, whereas the control group attended 4.5 hours of lectures. Each participant had to perform a simple (pre-evaluation) and a more complex (post-evaluation) catheter intervention on a pulsatile coronary flow model in a catheterization laboratory. All procedures were videotaped, analyzed, and rated by 3 expert interventionalists, who were blinded to the randomization. To assess the individual performance level, a "skills score" was determined, comprising 14 performance characteristics (5-level Likert scale, maximum score of 70 points). RESULTS: The "skills score" increased by 5.8 +/- 6.1 points in the VR simulation group and decreased by 6.7 +/- 8.4 in the control group (P = 0.003) from the simple stenosis at pre- to the more complex lesion at post-evaluation demonstrating the effectiveness of simulation-based training. CONCLUSION: This pilot study suggests that curriculum-based mentored VR simulation training improves the performance level of cardiology fellows in coronary interventions. Further investigation to evaluate the effect on clinical outcomes is warranted. PMID- 26671630 TI - Inductive effects of 10 and 12-vertex closo-carborane anions: cluster size and charge make a difference. AB - A phosphine containing a 10-vertex carborane anion substituent and its subsequent ligation to a Rh(I) carbonyl complex is reported. The complex is characterized by NMR spectroscopy and a single crystal X-ray diffraction study. In addition, the inductive effects of both 10 and 12 vertex C-functionalized closo-carborane anions are elucidated via I.R. analysis of the CO stretching frequencies of two Rh carbonyl complexes. Unlike C-functionalized neutral o-carborane the 10 and 12 vertex carborane anions are both strong electron donor substituents. PMID- 26671628 TI - Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression. AB - In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty. PMID- 26671631 TI - Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells. AB - BACKGROUND: There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE: To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS: Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day * 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS: ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 +/- 4.78 days) than those receiving F3.CD (21.5 +/- 1.75 days) or F3.CD-TK debris (19.3 +/- 0.85 days; n = 4/group; P < .05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION: Dual gene engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG. ABBREVIATIONS: 5FC, 5-fluorocytosineBBB, Basso, Beattie, and BresnahanCD, cytosine deaminaseDP, diastolic blood pressureGCV, ganciclovir; hNSCs, human neural stem cellsISCG, intramedullary spinal cord gliomasMAP, mean arterial blood pressureNSCs, neural stem cellsSP, systolic blood pressureTK, thymidine kinase. PMID- 26671633 TI - The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms: A Prospective Cohort Study. AB - BACKGROUND: We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA). OBJECTIVE: To determine the risk of seizure after discharge from surgery for UIA. METHODS: A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases. There were 726 cases of UIA (excluding cases proximal to the superior cerebellar artery on the vertebrobasilar system) identified and analyzed. Cox proportional hazards regression models and Kaplan-Meier life table analyses were generated assessing risk factors. RESULTS: Preoperative seizure history and complication of aneurysm repair were the only risk factors found to be significant. The risk of first seizure after discharge from hospital following surgery for patients with neither preoperative seizure, treated middle cerebral artery aneurysm, nor postoperative complications (leading to a modified Rankin Scale score >1) was <0.1% and 1.1% at 12 months and 7 years, respectively. The risk for those with preoperative seizures was 17.3% and 66% at 12 months and 7 years, respectively. The risk for seizures with either complications (leading to a modified Rankin Scale score >1) from surgery or treated middle cerebral artery aneurysm was 1.4% and 6.8% at 12 months and 7 years, respectively. These differences in the 3 Kaplan-Meier curves were significant (log-rank P < .001). CONCLUSION: The risk of seizures after discharge from hospital following surgery for UIA is very low when there is no preexisting history of seizures. If this result can be supported by other series, guidelines that restrict returning to driving because of the risk of postoperative seizures should be reconsidered. ABBREVIATIONS: MCA, middle cerebral arterymRS, modified Rankin ScaleUIA, unruptured intracranial aneurysms. PMID- 26671632 TI - Bypass Surgery for the Treatment of Dolichoectatic Basilar Trunk Aneurysms: A Work in Progress. AB - BACKGROUND: The treatment of dolichoectatic basilar trunk aneurysms has been ineffectual or morbid due to nonsaccular morphology, deep location, and involvement of brainstem perforators. Treatment with bypass surgery has been advocated to eliminate malignant hemodynamics and to stabilize aneurysm growth. OBJECTIVE: To validate that flow alteration with bypass and parent artery occlusion favorably impacts aneurysm progression. METHODS: Surgical management evolved in 3 phases, each with different hemodynamic alterations. RESULTS: During a 17-year period, 37 patients with dolichoectatic basilar trunk aneurysms were retrospectively identified, of whom 21 patients were observed, 12 treated immediately, and 4 selected for treatment after clinical progression. In phase 1, flow reversal was overly thrombogenic, despite heparin (N = 5, final mortality, 100%). In phase 2, flow reduction with intracranial-to-intracranial bypass was safer than flow reversal, but did not prevent progressive aneurysm enlargement (N = 3, final mortality 67%). In phase 3, distal clip occlusion of the basilar trunk aneurysm preserved anterograde flow in the aneurysm without rupture, but reduced flow threatened perforator patency, despite treatment with clopidogrel (N = 8, final mortality 62%). CONCLUSION: Shifting treatment strategy for dolichoectatic basilar trunk aneurysms improved surgical (80% to 50%) and final mortalities (100% to 62%), with stabilization of aneurysms in the phase 3 survivors. Good outcomes are determined by perforator preservation and mitigating aneurysm thrombosis. Occlusion techniques with increased distal run-off seem to benefit perforators. The treatment of dolichoectatic basilar trunk aneurysms can advance through concentrated management in dedicated centers, concerted efforts to study morphology and hemodynamics with computational methods, and widespread collection of registry data. ABBREVIATIONS: 4D PC-MRI, time-resolved phase-contrast MRIAICA, anterior inferior cerebellar arteryCE-MRA, high-resolution contrast-enhanced MR angiographyEC-IC, extracranial-to-intracranial bypassMCA, middle cerebral arteryMR, magnetic resonancemRS, modified Rankin ScalePCA, posterior cerebral arteryPICA, posterior inferior cerebellar arterySCA, superior cerebellar arterySTA, superficial temporal arteryVA, vertebral artery. PMID- 26671634 TI - To Treat or Not to Treat M2 Occlusions? The Question (and Answer) From a Single Institution. AB - BACKGROUND: Occlusions of the M2 segment of the middle cerebral artery may cause significant clinical effects, especially when occurring in the dominant cerebral hemisphere, yet endovascular treatment of these lesions remains controversial. OBJECTIVE: To examine the safety and efficacy of endovascular treatment of M2 occlusions at our institution. METHODS: We retrospectively examined radiographic and clinical data of 53 patients presenting with M2 occlusions to our institution. RESULTS: Successful recanalization (Thrombolysis in Cerebral Infarction grade 2b or 3) was achieved in 40 patients (76.9%). No symptomatic intracranial hemorrhage occurred. The mean National Institutes of Health Stroke Scale score at discharge was 6.4 (median, 5.5). In the 38 patients who had follow up after discharge, the mean follow-up duration was 11.1 months (range, 0.5-36.5 months) and mean National Institutes of Health Stroke Scale score was 3.5 (median, 1). CONCLUSION: The results of our single-institution experience suggest that endovascular therapy for M2 occlusions is safe and effective. Additional evaluation with randomized, controlled studies is warranted. ABBREVIATIONS: ADAPT, direct aspiration first-pass techniqueECASS, European-Australasian Cooperative Acute Stroke StudyICH, intracranial hemorrhageIMS, Interventional Management of StrokeMERCI, Mechanical Embolus Removal in Cerebral IschemiamRS, modified Rankin ScaleNIHSS, National Institutes of Health Stroke ScalePROACT, Prolyse in Acute Cerebral ThromboembolismTICI, Thrombolysis in Cerebral Infarctiont-PA, tissue-type plasminogen activator. PMID- 26671635 TI - Commentary: ORACLE Stroke Study: Opinion Regarding Acceptable Outcome Following Decompressive Hemicraniectomy for Ischaemic Stroke. PMID- 26671636 TI - Commentary: ORACLE Stroke Study: Opinion Regarding Acceptable Outcome Following Decompressive Hemicraniectomy for Ischaemic Stroke. PMID- 26671637 TI - Commentary: ORACLE Stroke Study: Opinion Regarding Acceptable Outcome Following Decompressive Hemicraniectomy for Ischaemic Stroke: Informed Consent When Surgical Outcomes Are Expected to Be Poor. PMID- 26671639 TI - A Hexameric Cationic Copper(II) Metallacrown as a Pertechnetate and Perrhenate Scavenger. AB - Materials based on the cationic copper(II) hexanuclear 18-membered metallacrown [18-MCCuII-N(2ph)-6](6+) (2phH=2-piconyl hydrazide) and tetrafluoroborate, perchlorate, nitrate, sulfate, and perrhenate anions were prepared by an easy method in aqueous medium. Single-crystal X-ray characterization of six members of this new family of complexes showed that the anions are attached to the metallacrown by direct coordination to a copper cation or by hydrogen-bonding interaction with the center of the hexamer. The stable cationic nature of the complexes and their ability to bind different anions allows them to adsorb and immobilize environmentally relevant anions such as MO4(-) (M=Tc, Re). The MO4(-) trapping capacities suggest that these materials would be useful in the treatment of oxoanionic contaminants in water. PMID- 26671638 TI - N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size. AB - Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (betamys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine betamys (Delta17betamys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Delta43alphamys). Step-size and step-frequency were measured using the Qdot motility assay. Both Delta17betamys and Delta43alphamys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID- 26671640 TI - Rap2b promotes proliferation, migration, and invasion of lung cancer cells. AB - Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer. PMID- 26671641 TI - Sec61: A static framework for membrane-protein insertion. PMID- 26671642 TI - Solution Synthesis of Thiospinel CuCo2S4 Nanoparticles. AB - CuCo2S4 is an important mixed-metal spinel-type sulfide that is typically synthesized using high-temperature solid-state reactions, which produce agglomerated particles with low surface areas that are not optimal for applications such as heterogeneous catalysis. Here, we show that highly crystalline and nonagglomerated colloidal CuCo2S4 nanoparticles can be synthesized in solution at 200 degrees C, which is significantly lower than previously reported methods. The CuCo2S4 nanoparticles were found to be highly active electrocatalysts for the oxygen evolution reaction (OER) under strongly alkaline conditions (1.0 M KOH, pH 14), requiring an OER overpotential of 395 mV to produce a current density of 10 mA cm(-2). X-ray photoelectron spectroscopy (XPS) studies showed evidence of oxide formation, suggesting, in conjunction with the observed electrocatalytic properties, that the mixed-metal sulfides may serve as precursors to oxides and/or hydroxides, which are likely to be the catalytically active species. PMID- 26671643 TI - Out-of-plane structural flexibility of phosphorene. AB - Phosphorene has been rediscovered recently, establishing itself as one of the most promising two-dimensional group-V elemental monolayers with direct band gap, high carrier mobility, and anisotropic electronic properties. In this paper, surface buckling and its effect on its electronic properties are investigated by using molecular dynamics simulations together with density functional theory calculations. We find that phosphorene shows superior structural flexibility along the armchair direction allowing it to have large curvatures. The semiconducting and direct band gap nature are retained with buckling along the armchair direction; the band gap decreases and transforms to an indirect band gap with buckling along the zigzag direction. The structural flexibility and electronic robustness along the armchair direction facilitate the fabrication of devices with complex shapes, such as folded phosphorene and phosphorene nano scrolls, thereby offering new possibilities for the application of phosphorene in flexible electronics and optoelectronics. PMID- 26671644 TI - [Estimation of the Palliative Care Needs and the Extent of Coverage by Specialized Outpatient Palliative Care Teams in Selected Regions of Westphalia Lippe]. AB - BACKGROUND: Data to estimate the palliative care needs and its outpatient coverage are of public health interest. METHODS: The theoretical palliative care needs were determined on the basis of a population with advanced cancer in selected regions of Westphalia (Germany); information from evaluated death certificates issued in 2011 in the cities of Bochum (BO) and Muenster (MS) and the rural districts of Coesfeld (COE) and Borken (BOR) were used for the analysis. The number of patients thus assessed was linked to anonymized data from the regional palliative home care teams and an estimate was made on the extent of palliative care provision. RESULTS: A total of 12,424 death certificates from 2011 were evaluated. In 22.1% (n=2,751), palliative care needs before death can be assumed. In the same year, 2,396 patients were cared for by the regional palliative home care teams, with 1,288 patients dying of cancer. The coverage of outpatient palliative care was calculated as follows: BO 54.2% (567/1,046), MS 60.6% (385/635), COE 54.4% (210/386), BOR 18.4% (126/684). CONCLUSIONS: One in 5 individuals has a need for palliative care before death. In statistical terms, more than 50% of tumor patients were cared for by regional palliative home care teams in the cities of Bochum and Muenster and the rural district of Coesfeld. By contrast, the degree of palliative care was less than 20% in the rural district of Borken. PMID- 26671645 TI - [Patient Satisfaction as a Measure of Quality of Patient Care - Comparison between a University Hospital and a General Hospital]. AB - Objective: The aim of the study was to compare the satisfaction of patients of a general hospital with a university hospital. A patient satisfaction index was calculated based on the assessed levels of satisfaction. In general, higher satisfaction could lead to increased competitiveness and improved cost efficiency for achieving profitability. Methods: The authors developed and administered a questionnaire on distinct parameters presumed to reflect the quality of the hospital stay to patients of a university hospital (University Hospital of Bonn, UKB, 1 224 beds) and a general hospital (Johanniterkrankenhaus, Bonn, JKH, 364 beds). Data were collected anonymously. Patient satisfaction and the relative importance of each parameter were assessed. The quotient of both parameters yields the patient satisfaction index (PZI). In order to account for possible differences in patient demands, statistical analysis was performed. Results: The demands and wishes, satisfaction and importance of the retrieved parameters did not differ significantly between the patients of the hospitals in any of aspects assessed (information, participation, contact and comfort during the hospital stay). The study showed that communication and the contact to physicians and nurses was significantly more important for the patients than comfort (each p<0.001). The highest PZI were found in the categories entertainment (UKB 1.02; JKH 1.25) and contact to the nursing personnel (PZI UKB 0.94; PZI JKH 0.96). The standard of medical-technical care (UKB 0.93; JKH 0.95) was also highly ranked by patients of both hospitals. Needs for improvement related especially to the communication of errors (UKB 0.33; JKH 0.31). Discussion: Surveillance of patient wishes and criticism may result in a more patient-oriented care on a daily basis. Scrutinizing the resources employed may lead to more efficient use of resources and personnel and thus help cut costs and improve the attractiveness of hospitals. PMID- 26671646 TI - [Comparison of Costs and Revenues in Conservative and Invasive Treatment in Cardiology: a Contribution Margin Analysis]. AB - Aim of the study: Direct costing is a specialized form of cost analysis well suited for medical areas with DRG-orientated flat rate payments. By comparing case-related variable costs and payments, it is possible to compare the economic benefits of different medical treatments. This aim was pursued by developing a direct costing concept and by its application to invasively and non-invasively treated cardiac patients. Methods: The entire database comprised 7 330 cases of a tertiary cardiac center between 2007 and 2011. It was derived from databases of the hospital information system, the materials management department and the catheter laboratory. On the revenue side, DRG payments were included. Costs related to heart catheterization such as material, personnel and maintenance expenses were considered to be variable costs. Contribution margins and relative contribution margins were calculated by introducing the length of hospital stay as a time reference. Results: During the observation period, caseload and annual revenues increased by about 20 percent. Contribution margins were higher in invasively than in non-invasively treated patients (2 097+/-1 590 vs. 1 614+/-1 105 ?; p<0,001). However, the relative relation of both patient groups was not altered during the observation period. A remarkable shortening of the duration of catheter laboratory examinations was observed between 2007 and 2011 (46,2+/-39,1 auf 36,7+/-33,5 min; p<0,001). In the same period, relative contribution margins increased from 461+/-306 to 530+/-335 ? (p<0,001). Conclusions: Within existing supply structures, direct costing is a useful tool for economic comparison of different treatment services. Furthermore, temporal constraints of an economic bottleneck can be easily monitored and tackled with the help of time management tools. PMID- 26671647 TI - Effects of non-carious cervical lesion size, occlusal loading and restoration on biomechanical behaviour of premolar teeth. AB - BACKGROUND: Information on fracture biomechanics has implications in materials research and clinical practice. The aim of this study was to analyse the influence of non-carious cervical lesion (NCCL) size, restorative status and direction of occlusal loading on the biomechanical behaviour of mandibular premolars, using finite element analysis (FEA), strain gauge tests and fracture resistance tests. METHODS: Ten buccal cusps were loaded on the outer and inner slopes to calculate the strain generated cervically. Data were collected for healthy teeth at baseline and progressively at three lesion depths (0.5 mm, 1.0 mm and 1.5 mm), followed by restoration with resin composite. The magnitude and distribution of von Mises stress and maximum principal stress were simulated at all stages using FEA, and fracture strength was also determined (n = 7 per group). RESULTS: There were significant effects of the lesion size and loading directions on stress, strain and fracture resistance (p < 0.05). Fracture resistance values decreased with increase in lesion size, but returned to baseline with restorations. CONCLUSIONS: Combined assessment of computer-based and experimental techniques provide an holistic approach to characterize the biomechanical behaviour of teeth with both unrestored and restored NCCLs. PMID- 26671648 TI - Characterization of Cell Wall Components and Their Modifications during Postharvest Storage of Asparagus officinalis L.: Storage-Related Changes in Dietary Fiber Composition. AB - Changes in cell wall composition during storage of plant foods potentially alter the physiological effects of dietary fiber components. To investigate postharvest cell wall modifications of asparagus and their consequences in terms of insoluble dietary fiber structures, asparagus was stored at 20 and 1 degrees C for different periods of time. Structural analyses demonstrated postharvest changes in the polysaccharide profile, dominated by decreased portions of galactans. Increasing lignin contents correlated with compositional changes (monolignol ratios and linkage types) of the lignin polymer as demonstrated by chemical and two-dimensional nuclear magnetic resonance (2D-NMR) methods. Depending on the storage time and temperature, syringyl units were preferentially incorporated into the lignin polymer. Furthermore, a drastic increase in the level of ester linked phenolic monomers (i.e., p-coumaric acid and ferulic acid) and polymer cross-links (di- and triferulic acids) was detected. The attachment of p-coumaric acid to lignin was demonstrated by 2D-NMR experiments. Potential consequences of postharvest modifications on physiological effects of asparagus dietary fiber are discussed. PMID- 26671649 TI - Air quality in Yanbu, Saudi Arabia. AB - Yanbu, on the Red Sea, is an affluent Saudi Arabian industrial city of modest size. Substantial effort has been spent to balance environmental quality, especially air pollution, and industrial development. We have analyzed six years of observations of criteria pollutants O3, SO2, particles (PM2.5 and PM10) and the known ozone precursors-volatile organic compounds (VOCs) and nitrogen oxides (NOx). The results suggest frequent VOC-limited conditions in which ozone concentrations increase with decreasing NOx and with increasing VOCs when NOx is plentiful. For the remaining circumstances ozone has a complex non-linear relationship with the VOCs. The interactions between these factors at Yanbu cause measurable impacts on air pollution including the weekend effect in which ozone concentrations stay the same or even increase despite significantly lower emissions of the precursors on the weekends. Air pollution was lower during the Eids (al-Fitr and al-Adha), Ramadan and the Hajj periods. During Ramadan, there were substantial night time emissions as the cycle everyday living is almost reversed between night and day. The exceedances of air pollution standards were evaluated using criteria from the U.S. Environmental Protection Agency (EPA), World Health Organization (WHO), the Saudi Presidency of Meteorology and Environment (PME) and the Royal Commission Environmental Regulations (RCER). The latter are stricter standards set just for Yanbu and Jubail. For the fine particles (PM2.5), an analysis of the winds showed a major impact from desert dust. This effect had to be taken into account but still left many occasions when standards were exceeded. Fewer exceedances were found for SO2, and fewer still for ozone. The paper presents a comprehensive view of air quality at this isolated desert urban environment. IMPLICATIONS: Frequent VOC-limited conditions are found at Yanbu in Saudi Arabia that increase ozone pollution if NOx is are reduced. In this desert environment, increased nightlife produces the highest levels of VOCs and NOx at night rather than the day. The effects increase during Ramadan. Fine particles peak twice a day-the morning peak is caused by traffic and increases with decreasing wind, potentially representing health concerns, but the larger afternoon peak is caused by the wind, and it increases with increasing wind speeds. These features suggest that exposure to pollutants must be redefined for such an environment. PMID- 26671650 TI - Shiga toxigenic and enteropathogenic Escherichia coli in water and fish from pay to-fish ponds. AB - Escherichia coli is part of the normal microflora of the intestines of mammals. However, among the enteric pathogens, it is one of the leading causes of intestinal diseases, especially Shiga toxigenic E. coli, which can cause diarrhoea, haemorrhagic colitis and complications like haemolytic uraemic syndrome and thrombotic thrombocytopaenic purpura. Escherichia coli is considered a serious public health problem. Water and fish samples were subjected to biochemical tests to confirm the presence of E. coli and by PCR to verify the presence of pathogenic strains (O157, enteropathogenic and shiga toxigenic) in water and fish (skin, gastrointestinal tract and muscles) from pay-to-fish ponds located in the Corrego Rico watershed in the northeastern region of the state of Sao Paulo, Brazil. Of the 115 E. coli isolates from fish or water, five (4.34%) contained eae and stx2 genes, one had only the eae gene and two had the stx1 gene. An isolate containing the stx2 gene was also found in the water sample. In addition, eight isolates (6.95%) from the fish gastrointestinal tract contained rfbEO157:H7 (O157 gene), and three (2.61%) contained stx2 and eae genes, demonstrating the potential risk to the environment and public health. The results provide useful basic information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population. SIGNIFICANCE AND IMPACT OF THE STUDY: Pay-to fish ponds are a common commercial activity in Brazil. Samples of water and Oreochromis niloticus were examined by PCR to detect the presence of pathogenic strains of Escherichia coli (O157, enteropathogenic and shiga toxigenic). Several pathogenic strains were detected in this study, providing useful epidemiological information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population. PMID- 26671651 TI - Insight into Pre-Clinical Models of Traumatic Brain Injury Using Circulating Brain Damage Biomarkers: Operation Brain Trauma Therapy. AB - Operation Brain Trauma Therapy (OBTT) is a multicenter pre-clinical drug screening consortium testing promising therapies for traumatic brain injury (TBI) in three well-established models of TBI in rats--namely, parasagittal fluid percussion injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI). This article presents unique characterization of these models using histological and behavioral outcomes and novel candidate biomarkers from the first three treatment trials of OBTT. Adult rats underwent CCI, FPI, or PBBI and were treated with vehicle (VEH). Shams underwent all manipulations except trauma. The glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in blood at 4 and 24 h, and their delta 24-4 h was calculated for each marker. Comparing sham groups across experiments, no differences were found in the same model. Similarly, comparing TBI + VEH groups across experiments, no differences were found in the same model. GFAP was acutely increased in injured rats in each model, with significant differences in levels and temporal patterns mirrored by significant differences in delta 24-4 h GFAP levels and neuropathological and behavioral outcomes. Circulating GFAP levels at 4 and 24 h were powerful predictors of 21 day contusion volume and tissue loss. UCH-L1 showed similar tendencies, albeit with less robust differences between sham and injury groups. Significant differences were also found comparing shams across the models. Our findings (1) demonstrate that TBI models display specific biomarker profiles, functional deficits, and pathological consequence; (2) support the concept that there are different cellular, molecular, and pathophysiological responses to TBI in each model; and (3) advance our understanding of TBI, providing opportunities for a successful translation and holding promise for theranostic applications. Based on our findings, additional studies in pre-clinical models should pursue assessment of GFAP as a surrogate histological and/or theranostic end-point. PMID- 26671653 TI - A multilaboratory study on the variability of bovine semen analysis. AB - To evaluate the variability of semen analysis, five replicates of 10 different bovine frozen semen batches were coded with different identification numbers and submitted to various laboratories for evaluation. Three studies were conducted: study I included eight laboratories in semen processing centers in the United States; study II included one laboratory in one semen processing center and five veterinary university laboratories in the United States; and study III included five veterinary university laboratories in Brazil. Evaluation methodology, sample classification criteria, and reporting format varied considerably among laboratories. There were laboratory effects (P < 0.05) on sperm concentration, motility, and morphology results in all studies. When Bland-Altman plots were evaluated, differences in sperm concentration were approximately between -5 and +5 * 10(6) sperm/mL in study I, when the same method of evaluation was used by all laboratories but ranged between -30 and +30 * 10(6) sperm/mL in studies II and III. Differences in the proportions of motile sperm were approximately -30% to +30%, and differences in the proportion of normal sperm were -15% to +15% in studies I and II; these differences were -15% to +15% and -10% to +10%, respectively, in study III. Mean absolute (one tail) proportional differences in estimates across all laboratories ranged from 9% to 31%, 16% to 37%, and 9% to 14% for sperm concentration, motile sperm, and normal sperm across studies; much larger (48%-86%) differences were observed for sperm abnormality categories. Intralaboratory and interlaboratory precision varied considerably across laboratories and seemed to be at least in part related to methods used for evaluation; precision was better when the NucleoCounter was used for evaluation of sperm concentration, whereas the use of computer-assisted sperm analysis for evaluation of sperm motility resulted in greater precision in some but not all laboratories. None of the laboratories that classified samples as satisfactory or unsatisfactory achieved complete consistency for all replicates within all batches. In addition, consistent classification among laboratories was observed for just three batches in studies II and III. These observations put the reliability of semen analysis in check and make it very difficult, if not impossible, to meaningfully interpret evaluation results. PMID- 26671652 TI - TATA boxes in gene transcription and poly (A) tails in mRNA stability: New perspective on the effects of berberine. AB - Berberine (BBR) is a natural compound with variable pharmacological effects and a broad panel of target genes. We investigated berberine's pharmacological activities from the perspective of its nucleotide-binding ability and discovered that BBR directly regulates gene expression by targeting TATA boxes in transcriptional regulatory regions as well as the poly adenine (poly (A)) tail at the mRNA terminus. BBR inhibits gene transcription by binding the TATA boxes in the transcriptional regulatory region, but it promotes higher levels of expression by targeting the poly (A) tails of mRNAs. The present study demonstrates that TATA boxes and poly (A) tails are the first and second primary targets by which BBR regulates gene expression. The final outcome of gene regulation by BBR depends on the structure of the individual gene. This is the first study to reveal that TATA boxes and poly (A) tails are direct targets for BBR in its regulation of gene expression. Our findings provide a novel explanation for the complex activities of a small molecule compound in a biological system and a novel horizon for small molecule-compound pharmacological studies. PMID- 26671654 TI - Xpert MTB/Rif for the diagnosis of extrapulmonary tuberculosis--an experience from a tertiary care centre in South India. AB - OBJECTIVE: The Xpert MTB/Rif, with a detection limit of 131 CFU/ml, plays a valuable role in the diagnosis of extrapulmonary tuberculosis, both susceptible and resistant. This study aims at evaluating the Xpert MTB/Rif for the same, at a tertiary care centre in south India, assessing it against both culture and a composite gold standard (CGS). METHODS: We tested consecutive samples from patients suspected of extrapulmonary tuberculosis with Xpert MTB/Rif, evaluated its sensitivity and specificity against solid and/or liquid culture and CGS. An individual analysis of different sample types (tissue biopsies, fluids, pus, lymph node biopsies and CSF) given an adequate sample size, against both culture and CGS, was also performed. RESULTS: In total, 494 samples were analysed against culture. Compared to culture, the sensitivity of Xpert MTB/Rif was 89% (95% CI 0.81-0.94) and its specificity was 74% (95% CI 0.70-0.78). When Xpert MTB/Rif was compared to the CGS, pooled sensitivity was 62% (95% CI 0.56-0.67) and specificity was 100% (95% CI 0.91-1.00). CONCLUSION: This assay performs better than the currently available conventional laboratory methods. The rapidity with which results are obtained is an added advantage, and its integration into a routine diagnostic protocol must be considered. PMID- 26671655 TI - A novel PR10 promoter from Erianthus arundinaceus directs high constitutive transgene expression and is enhanced upon wounding in heterologous plant systems. AB - In genetic engineering, inducible promoters play an important role as the expression of genes driven by them can be turned on or off under situations like biotic or abiotic factors. There are few reports on inducible promoters that can be employed in the development of transgenic plants, particularly in sugarcane. In the present study, four wound inducible genes (Chitinase, PR1A, PR10 and HRGP) were selected and were amplified from Erianthus arundinaceus, a distant relative of sugarcane. In order to determine the gene that is highly induced upon wounding, RT-qPCR was performed, which showed that PR10 gene expression was instantaneous and higher upon wounding when compared to the other three genes. Using the random amplification of genomic ends technique, a 592 bp promoter sequence was obtained and in silico analysis of the upstream regulatory region revealed a 469 bp promoter and 123 bp of 5' untranslated region (UTR). Functional analyses of the promoter sequence (with and without 5' UTR) in tobacco, rice and sugarcane using beta-glucuronidase (GUS) as the reporter gene revealed the constitutive and inducible nature of the PR10 promoter. Our studies have demonstrated that the PR10 promoter, though highly constitutive, was quickly induced upon wounding as well as on treatment with abscisic acid and methyl jasmonate hormones. This is the first report on the isolation and characterization of a PR10 promoter from a wild grass and is expected to have application for development of transgenic plants. PMID- 26671656 TI - N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing. AB - The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) using a uni-directional wound healing assay. NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans. PMID- 26671657 TI - Eosinophilic fasciitis with severe joint contracture in a patient with bladder cancer and B-cell lymphoma. PMID- 26671659 TI - Determination of the minimum infusion rate of propofol required to prevent purposeful movement of the extremities in response to a standardized noxious stimulus in goats. AB - OBJECTIVE: To determine the minimum infusion rate (MIR) of propofol required to prevent purposeful movement in response to a standardized stimulus in goats. STUDY DESIGN: Prospective, experimental study. ANIMALS: Eight healthy goats (four does, four wethers). METHODS: Anaesthesia was induced with 4 mg kg(-1) propofol intravenously (IV). A continuous IV infusion of propofol at 0.6 mg kg(-1) minute(-1) was initiated immediately to maintain anaesthesia. Following endotracheal intubation, goats breathed spontaneously via a circle breathing system delivering supplementary oxygen. The initial propofol infusion rate was maintained for 30 minutes before responses to noxious stimulation provided by clamping the proximal part of the claw with a Vulsellum forceps for 60 seconds were tested. In the presence or absence of purposeful movements of the extremities, the infusion rate was increased or reduced by 0.1 mg kg(-1) minute( 1) and held constant for 30 minutes before claw clamping was repeated. The propofol MIR for each goat was calculated as the mean of the infusion rates that allowed and abolished movement. Basic cardiopulmonary parameters were monitored, recorded and tested for statistical significance using Wilcoxon's signed rank test with Bonferroni adjustment for multiple testing. The quality of recovery from anaesthesia was assessed and scored. RESULTS: The median MIR of propofol was 0.45 mg kg(-1) minute(-1) (range: 0.45-0.55 mg kg(-1) minute(-1) ). Induction and recovery were free of adverse behaviour. No statistically significant cardiopulmonary changes in comparison with baseline were observed, but clinically relevant hypoxaemia at 2 minutes after induction of anaesthesia was consistently observed. Chewing during anaesthesia was observed in three goats. Median times to extubation and standing were 3 minutes (range: 2-6 minutes) and 10 minutes (range: 7-21 minutes), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol induction and maintenance of general anaesthesia minimally compromise cardiopulmonary function when oxygen is supplemented in goats. PMID- 26671660 TI - Infants' acceptance of phonotactically illegal word forms as object labels. AB - We investigated 16- and 20-month-olds' flexibility in mapping phonotactically illegal words to objects. Using an associative word-learning task, infants were presented with a training phase that either highlighted or did not highlight the referential status of a novel label. Infants were then habituated to two novel objects, each paired with a phonotactically illegal Czech word. When referential cues were provided, 16-, but not 20-month-olds, formed word-object mappings. In the absence of referential cues, infants of both ages failed to map the novel words. These findings illustrate the complex interplay between infants' developing sound system and their word learning abilities. PMID- 26671658 TI - Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. AB - Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation. PMID- 26671661 TI - Controllable Fabrication and Optical Properties of Uniform Gadolinium Oxysulfate Hollow Spheres. AB - Uniform gadolinium oxysulfate (Gd2O2SO4) hollow spheres were successfully fabricated by calcination of corresponding Gd-organic precursor obtained via a facile hydrothermal process. The Gd2O2SO4 hollow spheres have a mean diameter of approximately 550 nm and shell thickness in the range of 30-70 nm. The sizes and morphologies of as-prepared Gd2O2SO4 hollow spheres could be deliberately controlled by adjusting the experimental parameters. Eu-doped Gd2O2SO4 hollow spheres have also been prepared for the property modification and practical applications. The structure, morphology, and properties of as-prepared products were characterized by XRD, TEM, HRTEM, SEM and fluorescence spectrophotometer. Excited with ultraviolet (UV) pump laser, successful downconversion (DC) could be achieved for Eu-doped Gd2O2SO4 hollow spheres. PMID- 26671663 TI - Burn wound cooling with tap water: is it safe in developing countries or not? PMID- 26671662 TI - Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil Induced Cardioprotection in Rats. AB - BACKGROUND: Mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro. METHODS: Male Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 MUM) was administered over 10 min before the beginning of ischemia. The mBKCa channel inhibitor paxilline (1 MUM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 MUM). Myocardial cGMP concentration was measured by ELISA. Data (mean+/-SD) were analysed with a one and two-way analysis of variance as appropriate. RESULTS: In control animals infarct size was 52+/-8%. Sildenafil increased cGMP concentration and reduced infarct size to 35+/-6% (P<0.05 vs. control). Paxilline and KT5823 completely blocked sildenafil-induced cardioprotection (paxilline+sildenafil: 50+/-8%, KT5823+sildenafil: 45+/-8%; both P<0.05 vs. sildenafil). Functional heart parameters and coronary flow were not different between the study groups. CONCLUSION: This study shows that in male rats protein kinase G-dependent opening of mBKCa channels plays a pivotal role in sildenafil-induced cardioprotection. PMID- 26671664 TI - Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants. AB - Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhauser syndromes, Laurence-Moon syndrome, and Oliver McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29 degrees C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25 degrees C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila. PMID- 26671667 TI - Pre-constancy Vision in Infants. AB - Our visual system can easily estimate the constant color and material of external objects despite dynamic changes in the retinal image across viewpoints and illuminations in natural scenes. It is commonly believed that this high-level visual function, called "perceptual constancy," is acquired through postnatal learning [1], building upon low-level functions that have developed earlier, such as image discrimination. However, we demonstrate here that before developing perceptual constancy, 3- to 4-month-old infants have a striking ability to discriminate slight image changes due to illumination that are not salient for adults. These young infants lose this ability after 5 months of age and then develop an ability to perceive distal surface properties (glossy or matte) at 7-8 months of age. Moreover, we identify the transition period between these two functions at 5-6 months of age, wherein infants show difficulty in both image and surface discrimination. These findings support the notion that acquiring perceptual constancy leads to a loss of sensitivity to variant information, which is negligible for constant surface material perception. We suggest that the immature visual system may initially directly access local image features and then develops a complementary constant neural representation of the properties of an object. PMID- 26671668 TI - Forward Genetics Identifies a Requirement for the Izumo-like Immunoglobulin Superfamily spe-45 Gene in Caenorhabditis elegans Fertilization. AB - Fertilization is a conserved process in all sexually reproducing organisms whereby sperm bind and fuse with oocytes. Despite the importance of sperm-oocyte interactions in fertilization, the molecular underpinnings of this process are still not well understood. The only cognate ligand-receptor pair identified in the context of fertilization is sperm-surface Izumo and egg-surface Juno in the mouse [1]. Here we describe a genetic screening strategy to isolate fertilization mutants in Caenorhabditis elegans in order to generate a more complete inventory of molecules required for gamete interactions. From this screening strategy, we identified, cloned, and characterized spe-45, a gene that encodes an Izumo-like immunoglobulin superfamily protein. Mammalian Izumo is required for male fertility and has the same basic mutant phenotype as spe-45. Worms lacking spe-45 function produce morphologically normal and motile sperm that cannot fuse with oocytes despite direct contact in the reproductive tract. The power of this screen to identify proteins with ancient sperm functions suggests that characterization of additional mutants from our screen may reveal other deeply conserved components in fertility pathways and complement studies in other organisms. PMID- 26671669 TI - The Immunoglobulin-like Gene spe-45 Acts during Fertilization in Caenorhabditis elegans like the Mouse Izumo1 Gene. AB - The Caenorhabditis elegans spe-9 class genes, which show specific or predominant expression in the male germline, are indispensable for fertilization [1, 2]. However, due to the rapid evolution of genes involved in reproduction, we do not currently know if there are spe-9 class genes in mammals that play similar roles during fertilization to those found in C. elegans. In mice, the Izumo1 gene encodes a sperm-specific transmembrane (TM) protein with a single immunoglobulin (Ig)-like domain that is absolutely required for gamete fusion [3, 4]. In this study, we hypothesized that C. elegans has a new member of the spe-9 class genes coding for an IZUMO1-like protein. We screened C. elegans microarray data [5, 6] to identify male germline-enriched genes that encode membrane proteins with Ig like domains. A deletion (tm3715) in one such gene (F28D1.8) caused hermaphrodites to show a male germline-dependent self-sterility, so we have named it spe-45. Mutant spe-45 worms seemed to normally undergo spermatogenesis (spermatid production by meiosis) and spermiogenesis (spermatid activation into actively motile spermatozoa). spe-45 mutant spermatozoa, however, could not complete gamete fusion, which is a characteristic of all spe-9 class mutants [1, 2]. Moreover, spe-45 self-sterile worms were rescued by a transgene expressing chimeric SPE-45 protein in which its Ig-like domain was replaced by the Ig-like domain from mouse IZUMO1. Hence, C. elegans SPE-45 and mouse IZUMO1 appear to have retained a common function(s) that is required during fertilization. PMID- 26671670 TI - Energy-Efficient Information Transfer by Visual Pathway Synapses. AB - The architecture of computational devices is shaped by their energy consumption. Energetic constraints are used to design silicon-based computers but are poorly understood for neural computation. In the brain, most energy is used to reverse ion influxes generating excitatory postsynaptic currents (EPSCs) and action potentials. Thus, EPSCs should be small to minimize energy use, but not so small as to impair information transmission. We quantified information flow through the retinothalamic synapse in the visual pathway in brain slices, with cortical and inhibitory input to the postsynaptic cell blocked. Altering EPSC size with dynamic clamp, we found that a larger-than-normal EPSC increased information flow through the synapse. Thus, the evolutionarily selected EPSC size does not maximize retinal information flow to the cortex. By assessing the energy used on postsynaptic ion pumping and action potentials, we show that, instead, the EPSC size optimizes the ratio of retinal information transmitted to energy consumed. These data suggest maximization of information transmission per energy used as a synaptic design principle. PMID- 26671671 TI - Gut Microbiome Diversity among Cheyenne and Arapaho Individuals from Western Oklahoma. AB - Existing studies characterizing gut microbiome variation in the United States suffer from population ascertainment biases, with individuals of American Indian ancestry being among the most underrepresented. Here, we describe the first gut microbiome diversity study of an American Indian community. We partnered with the Cheyenne and Arapaho (C&A), federally recognized American Indian tribes in Oklahoma, and compared gut microbiome diversity and metabolic function of C&A participants to individuals of non-native ancestry in Oklahoma (NNIs). While the C&A and NNI participants share microbiome features common to industrialized populations, the C&A participants had taxonomic profiles characterized by a reduced abundance of the anti-inflammatory bacterial genus Faecalibacterium, along with a fecal metabolite profile similar to dysbiotic states described for metabolic disorders. American Indians are known to be at elevated risk for metabolic disorders. While many aspects of this health disparity remain poorly understood, our results support the need to further study the microbiome as a contributing factor. As the field of microbiome research transitions to therapeutic interventions, it raises concerns that the continued exclusion and lack of participation of American Indian communities in these studies will further exacerbate health disparities. To increase momentum in fostering these much needed partnerships, it is essential that the scientific community actively engage in and recruit these vulnerable populations in basic research through a strategy that promotes mutual trust and understanding, as outlined in this study. PMID- 26671673 TI - Mechanically Stretchable and Electrically Insulating Thermal Elastomer Composite by Liquid Alloy Droplet Embedment. AB - Stretchable electronics and soft robotics have shown unsurpassed features, inheriting remarkable functions from stretchable and soft materials. Electrically conductive and mechanically stretchable materials based on composites have been widely studied for stretchable electronics as electrical conductors using various combinations of materials. However, thermally tunable and stretchable materials, which have high potential in soft and stretchable thermal devices as interface or packaging materials, have not been sufficiently studied. Here, a mechanically stretchable and electrically insulating thermal elastomer composite is demonstrated, which can be easily processed for device fabrication. A liquid alloy is embedded as liquid droplet fillers in an elastomer matrix to achieve softness and stretchability. This new elastomer composite is expected useful to enhance thermal response or efficiency of soft and stretchable thermal devices or systems. The thermal elastomer composites demonstrate advantages such as thermal interface and packaging layers with thermal shrink films in transient and steady state cases and a stretchable temperature sensor. PMID- 26671674 TI - Cell-Derived Extracellular Matrix: Basic Characteristics and Current Applications in Orthopedic Tissue Engineering. AB - The extracellular matrix (ECM) is a dynamic and intricate microenvironment with excellent biophysical, biomechanical, and biochemical properties, which can directly or indirectly regulate cell proliferation, adhesion, migration, and differentiation, as well as plays key roles in homeostasis and regeneration of tissues and organs. The ECM has attracted a great deal of attention with the rapid development of tissue engineering in the field of regenerative medicine. Tissue-derived ECM scaffolds (also referred to as decellularized tissues and whole organs) are considered a promising therapy for the repair of musculoskeletal defects, including those that are widely used in orthopedics, although there are a few shortcomings. Similar to tissue-derived ECM scaffolds, cell-derived ECM scaffolds also have highly advantageous biophysical and biochemical properties, in particular their ability to be produced in vitro from a number of different cell types. Furthermore, cell-derived ECM scaffolds more closely resemble native ECM microenvironments. The products of cell-derived ECM have a wide range of biomedical applications; these include reagents for cell culture substrates and biomaterials for scaffolds, hybrid scaffolds, and living cell sheet coculture systems. Although cell-derived ECM has only just begun to be investigated, it has great potential as a novel approach for cell-based tissue repair in orthopedic tissue engineering. This review summarizes and analyzes the various types of cell-derived ECM products applied in cartilage, bone, and nerve tissue engineering in vitro or in vivo and discusses future directions for investigation of cell-derived ECM. PMID- 26671672 TI - Hepatocystin is Essential for TRPM7 Function During Early Embryogenesis. AB - Mutations in protein kinase C substrate 80K-H (PRKCSH), which encodes for an 80 KDa protein named hepatocystin (80K-H, PRKCSH), gives rise to polycystic liver disease (PCLD). Hepatocystin functions as the noncatalytic beta subunit of Glucosidase II, an endoplasmic reticulum (ER)-resident enzyme involved in processing and quality control of newly synthesized glycoproteins. Patients harboring heterozygous germline mutations in PRKCSH are thought to develop renal cysts as a result of somatic loss of the second allele, which subsequently interferes with expression of the TRP channel polycystin-2 (PKD2). Deletion of both alleles of PRKCSH in mice results in embryonic lethality before embryonic day E11.5. Here, we investigated the function of hepatocystin during Xenopus laevis embryogenesis and identified hepatocystin as a binding partner of the TRPM7 ion channel, whose function is required for vertebrate gastrulation. We find that TRPM7 functions synergistically with hepatocystin. Although other N glycosylated proteins are critical to early development, overexpression of TRPM7 in Xenopus laevis embryos was sufficient to fully rescue the gastrulation defect caused by loss of hepatocystin. We observed that depletion of hepatocystin in Xenopus laevis embryos decreased TRPM7 expression, indicating that the early embryonic lethality caused by loss of hepatocystin is mainly due to impairment of TRPM7 protein expression. PMID- 26671675 TI - Development of a Decision Aid for Patients With Advanced Heart Failure Considering a Destination Therapy Left Ventricular Assist Device. AB - OBJECTIVES: This study aimed to create decision aids (DAs) for patients considering a destination therapy left ventricular assist device (DT LVAD). BACKGROUND: Insertion of a DT LVAD is a major decision for patients with end stage heart failure. Patients facing decisions with complex trade-offs may benefit from high-quality decision support resources. METHODS: In accordance with the International Patient Decision Aid Standards guidelines and based on a needs assessment with stakeholders, we developed drafts of paper and video DAs. With input from patients, caregivers, and clinicians through alpha testing, we iteratively modified the DAs to ensure acceptability. RESULTS: We conducted semistructured interviews with 24 patients, 20 caregivers, and 24 clinicians to assess readability, bias, and usability of the DAs. Stakeholder feedback allowed us to integrate aspects critical to decision making around highly invasive therapies for life-threatening diseases, including addressing emotion and fear of death, using gain frames for all options that focus on living, highlighting palliative and hospice care, integrating the caregiver role, and using a range of balanced testimonials. After 19 iterative versions of the paper DA and 4 versions of the video DA, final materials were made available for wider use. CONCLUSIONS: We developed the first International Patient Decision Aid Standards-level DAs for DT LVAD. Given the extreme nature of this medical decision, we augmented traditional DA characteristics with nontraditional DA features to address a spectrum of cognitive, automatic, and emotional aspects of end-of-life decision making. Not only are the DAs important tools for those confronting end-stage heart failure, but the lessons learned will likely inform decision support for other invasive therapies. PMID- 26671677 TI - Heart Failure "End Result Cards": Solid B. PMID- 26671676 TI - Amino-Terminal Pro-B-Type Natriuretic Peptide for Diagnosis and Prognosis in Patients With Renal Dysfunction: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: This study sought to determine if amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has different diagnostic and prognostic utility in patients with renal dysfunction. BACKGROUND: Patients with renal dysfunction have higher NT-proBNP, which may complicate interpretation for diagnosis of acute decompensated heart failure (ADHF) or prognosis. METHODS: We searched MEDLINE and EMBASE through August 2014 for studies with a subgroup analysis by renal function of the diagnostic or prognostic ability of NT-proBNP. RESULTS: For diagnosis, 9 studies were included with 4,287 patients and 1,325 ADHF events. Patients were mostly divided into subgroups with and without renal dysfunction by an estimated glomerular filtration rate of 60 ml/min/1.73 m(2). In patients with renal dysfunction, the area under the curve (AUC) for NT-proBNP ranged from 0.66 to 0.89 with a median cutpoint of 1,980 pg/ml, while the AUC ranged from 0.72 to 0.95 with a cutpoint of 450 pg/ml in patients with preserved renal function. For prognosis, 30 studies with 32,203 patients were included, and mortality in patients with renal dysfunction (25.4%) was twice that of patients with preserved renal function (12.2%). The unadjusted pooled risk ratio for NT-proBNP and mortality was 3.01 (95% confidence interval [CI]: 2.53 to 3.58) in patients with preserved renal function and was similar in patients with renal dysfunction (3.25; 95% CI: 2.45 to 4.30). Upon meta-regression, heterogeneity was partially explained if patients with heart failure or coronary artery disease were enrolled. CONCLUSIONS: NT-proBNP retains utility for diagnosis of ADHF in patients with renal dysfunction with higher cutpoints. Elevated NT-proBNP confers a worse prognosis regardless of renal function. PMID- 26671678 TI - Reply: Heart Failure and Comorbidities. PMID- 26671679 TI - Heart Failure and Comorbidities. PMID- 26671680 TI - Detection of Helminth Eggs and Identification of Hookworm Species in Stray Cats, Dogs and Soil from Klang Valley, Malaysia. AB - The present study was conducted to determine the prevalence of helminth eggs excreted in the faeces of stray cats, dogs and in soil samples. A total of 505 fresh samples of faeces (from 227 dogs and 152 cats) and soil were collected. The egg stage was detected via microscopy after the application of formalin-ether concentration technique. Genomic DNA was extracted from the samples containing hookworm eggs and used for further identification to the species level using real time polymerase chain reaction coupled with high resolution melting analysis. Microscopic observation showed that the overall prevalence of helminth eggs among stray cats and dogs was 75.7% (95% CI = 71.2%-79.9%), in which 87.7% of dogs and 57.9% of cats were infected with at least one parasite genus. Five genera of heliminth eggs were detected in the faecal samples, including hookworms (46.4%), Toxocara (11.1%), Trichuris (8.4%), Spirometra (7.4%) and Ascaris (2.4%). The prevalence of helminth infections among stray dogs was significantly higher than that among stray cats (p < 0.001). Only three genera of helminths were detected in soil samples with the prevalence of 23% (95% CI = 15.1%-31%), consisting of hookworms (16.6%), Ascaris (4%) and Toxocara (2.4%). The molecular identification of hookworm species revealed that Ancylostoma ceylanicum was dominant in both faecal and soil samples. The dog hookworm, Ancylostoma caninum, was also detected among cats, which is the first such occurrence reported in Malaysia till date. This finding indicated that there was a cross-infection of A. caninum between stray cats and dogs because of their coexistent within human communities. Taken together, these data suggest the potential role of stray cats and dogs as being the main sources of environmental contamination as well as for human infections. PMID- 26671681 TI - A Comprehensive Study of Soft Palate Development in Mice. AB - Cleft palate is one of the most common congenital birth defects. Tremendous efforts have been made over the last decades towards understanding hard palate development. However, little is known about soft palate morphogenesis and myogenesis. Finding an appropriate surgical repair to restore physiological functions of the soft palate in patients with cleft palate is a major challenge for surgeons, and complete restoration is not always achievable. Here, we first analyzed the morphology, orientation and attachments of the four muscles of the murine soft palate and found that they are very similar to their counterparts in humans, validating the use of mus musculus as a model for future studies. Our data suggests that muscle differentiation extends from the lateral region to the midline following palatal fusion. We also detected an epithelial seam in the fusing soft palatal shelves, consistent with the process of fusion of the posterior palatal shelves, followed by degradation of the epithelial remnants. Innervation and vascularization are present mainly in the oral side of the soft palate, complementing the differentiated muscles. Cell lineage tracing using Wnt1 Cre;Zsgreenfl/fl mice indicated that all the tendons and mesenchyme embedding the soft palate muscles are neural crest-derived. We propose that the posterior attachment of the soft palate to the pharyngeal wall is an interface between the neural crest- and mesoderm-derived mesenchyme in the craniofacial region, and thus can serve as a potential model for the study of boundaries during development. Taken together, our study provides a comprehensive view of the development and morphology of the murine soft palate and serves as a reference for further molecular analyses. PMID- 26671682 TI - Cationic Oligo(thiophene ethynylene) with Broad-Spectrum and High Antibacterial Efficiency under White Light and Specific Biocidal Activity against S. aureus in Dark. AB - We designed and synthesized a novel oligo(thiophene ethynylene) (OTE) to investigate the antibacterial activities against Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Ralstonia solanacearum and Escherichia coli) bacteria in vitro by photodynamic therapy (PDT). Notably, OTE presents broad-spectrum and greatly high antibacterial activities after white light irradiation at nanogram per milliliter concentrations. The half inhibitory concentrations (IC50) values obtained for S. aureus, S. epidermidis, E. coli, and R. solanacearum are 8, 13, 24, and 52 ng/mL after illumination for 30 min, respectively, which are lower than that of other PDT agents. Interestingly, OTE shows the specific and very strong dark killing capability against S. aureus at the concentration of 180 ng/mL for 30 min, which is the highest efficiency biocide against S. aureus without the need of irradiation to date. The antibacterial mechanism investigated demonstrated that reactive oxygen species or singlet-oxygen generated by OTE kills bacteria irreversibly upon white light irradiation, and OTE as a v-type oligomer exerts its toxicity directly on destroying bacterial cytoplasmic membrane in the dark. Importantly, the OTE shows no cell cytotoxicity and excellent biocompatibility. The results indicate that it is potential to provide versatile applications in the efficient control of pathogenic organisms and specific application for killing S. aureus. PMID- 26671683 TI - Spatial Distortion in MRI-Guided Stereotactic Procedures: Evaluation in 1.5-, 3- and 7-Tesla MRI Scanners. AB - BACKGROUND: Magnetic resonance imaging (MRI) is replacing computed tomography (CT) as the main imaging modality for stereotactic transformations. MRI is prone to spatial distortion artifacts, which can lead to inaccuracy in stereotactic procedures. OBJECTIVE: Modern MRI systems provide distortion correction algorithms that may ameliorate this problem. This study investigates the different options of distortion correction using standard 1.5-, 3- and 7-tesla MRI scanners. METHODS: A phantom was mounted on a stereotactic frame. One CT scan and three MRI scans were performed. At all three field strengths, two 3 dimensional sequences, volumetric interpolated breath-hold examination (VIBE) and magnetization-prepared rapid acquisition with gradient echo, were acquired, and automatic distortion correction was performed. Global stereotactic transformation of all 13 datasets was performed and two stereotactic planning workflows (MRI only vs. CT/MR image fusion) were subsequently analysed. RESULTS: Distortion correction on the 1.5- and 3-tesla scanners caused a considerable reduction in positional error. The effect was more pronounced when using the VIBE sequences. By using co-registration (CT/MR image fusion), even a lower positional error could be obtained. In ultra-high-field (7 T) MR imaging, distortion correction introduced even higher errors. However, the accuracy of non-corrected 7-tesla sequences was comparable to CT/MR image fusion 3-tesla imaging. CONCLUSION: MRI distortion correction algorithms can reduce positional errors by up to 60%. For stereotactic applications of utmost precision, we recommend a co-registration to an additional CT dataset. PMID- 26671684 TI - Comparison of patient-controlled epidural analgesia and patient-controlled intravenous analgesia after spinal fusion surgery: a meta-analysis of randomized controlled trials. AB - BACKGROUND: The objective of this meta-analysis was to compare the efficacy and safety of patient-controlled epidural analgesia (PCEA) and patient-controlled intravenous analgesia (PCIA) in postoperative analgesia of spinal fusion surgery. METHODS: Potential academic articles were identified from the Cochrane Library, Medline (1966-2015.5), PubMed (1966-2015.5), Embase (1980-2015.5) and ScienceDirect (1966-2015.5). Gray studies were identified from the references of the included literature. Randomized controlled trials (RCTs) involving PCEA and PCIA after spinal fusion were included. Two independent reviewers performed independent data abstraction. I(2) statistic was used to assess heterogeneity. Fixed or random effects model was used for meta-analysis. RESULTS: Eight RCTs met the inclusion criteria. There was a better analgesic effect in patients with PCEA for postoperative VAS on the first day (P = 0.0005) and second day (P = 0.006). The patients with PCEA had a higher incidence of pruritus (P = 0.02) and paresthesia (P = 0.03) after surgery than those with PCIA. There was no statistically significant difference in postoperative VAS on the third day (P = 0.15), nausea (P = 0.74) or emesis (P = 0.37) between the two groups. CONCLUSIONS: After spinal fusion, the patients with PCEA have similar analgesic efficacy during the three postoperative days and a higher incidence of pruritus and paresthesia than those with PCIA. Due to the limited quality and data of the evidence currently available, more high-quality randomized controlled trials are required. PMID- 26671685 TI - Self-supported nanoporous NiCo2O4 nanowires with cobalt-nickel layered oxide nanosheets for overall water splitting. AB - Water splitting via the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in producing H2 and O2 is a very important process in the energy field. Developing an efficient catalyst which can be applied to both HER and OER is crucial. Here, a bifunctional catalyst, CFP/NiCo2O4/Co0.57Ni0.43LMOs, has been successfully fabricated. It exhibits remarkable performance for OER in 0.1 M KOH producing a current density of 10 mA cm(-2) at an overpotential of 0.34 V (1.57 V vs. RHE), better than that of the commercial Ir/C (20%) catalyst. Simultaneously, it also exhibits good catalytic performance for HER in 0.5 M H2SO4 producing a current density of 10 mA cm(-2) at an overpotential of 52 mV and a Tafel slope of 34 mV dec(-1), approaching that of the commercial Pt/C (20%) nanocatalyst. Particularly, CFP/NiCo2O4/Co0.57Ni0.43LMOs present better durability under harsh OER and HER cycling conditions than commercial Ir/C and Pt/C. Furthermore, an H type electrolyzer was fabricated by applying CFP/NiCo2O4/Co0.57Ni0.43LMOs as the cathode and anode electrocatalyst, which can be driven by a single-cell battery. This bifunctional catalyst will be very promising in overall water splitting. PMID- 26671686 TI - The generalist tick Ixodes ricinus and the specialist tick Ixodes trianguliceps on shrews and rodents in a northern forest ecosystem--a role of body size even among small hosts. AB - BACKGROUND: Understanding aggregation of ticks on hosts and attachment of life stages to different host species, are central components for understanding tick borne disease epidemiology. The generalist tick, Ixodes ricinus, is a well-known vector of Lyme borrelioses, while the specialist tick, Ixodes trianguliceps, feeding only on small mammals, may play a role in maintaining infection levels in hosts. In a northern forest in Norway, we aimed to quantify the role of different small mammal species in feeding ticks, to determine the extent to which body mass, even among small mammals, plays a role for tick load, and to determine the seasonal pattern of the two tick species. METHODS: Small mammals were captured along transects in two nearby areas along the west coast of Norway. All life stages of ticks were counted. Tick load, including both prevalence and intensity, was analysed with negative binomial models. RESULTS: A total of 359 rodents and shrews were captured with a total of 1106 I. ricinus (60.0 %) and 737 I. trianguliceps (40.4 %), consisting of 98.2 % larvae and 1.8 % nymphs of I. ricinus and 91.2 % larvae, 8.7 % nymphs and 0.1 % adult females of I. trianguliceps. Due to high abundance, Sorex araneus fed most of the larvae of both tick species (I. ricinus 61.9 %, I. trianguliceps 64.9 %) with Apodemus sylvaticus (I. ricinus 20.4 %, I. trianguliceps 10.0 %) and Myodes glareolus (I. ricinus 10.9 %, I. trianguliceps 9.5 %) as the next most important hosts. Individual A. sylvaticus and M. glareolus had higher infestation intensity than S. araneus, while Sorex minutus had markedly lower infestation intensity. The load of I. ricinus larvae and nymphs was related to body mass mainly up to ~10 g, while the load of I. trianguliceps was less dependent of body mass. The load of I. trianguliceps was higher in spring than in fall, while the seasonal pattern was reversed for I. ricinus with higher loads in fall. CONCLUSIONS: Body mass was important for explaining load of I. ricinus mainly up to a body mass of ~10 g across a range of smaller mammalian hosts. Consistent with earlier work elsewhere in Europe, we found the highest tick infestation intensity on the wood mouse A. sylvaticus. However, this rodent species fed only 20.4 % of all I. ricinus larvae, while the much more abundant S. araneus fed 61.9 %. Our study emphasizes an important quantitative role of the common shrew S. araneus as a main host to I. ricinus larvae and to both I. trianguliceps larvae and nymphs. The partly seasonal distinct attachment pattern of I. ricinus and I. trianguliceps is evidence for niche separation. PMID- 26671687 TI - Disease association and inter-connectivity analysis of human brain specific co expressed functional modules. AB - BACKGROUND: In the recent studies, it is suggested that the analysis of transcriptomic change of functional modules instead of individual genes would be more effective for system-wide identification of cellular functions. This could also provide a new possibility for the better understanding of difference between human and chimpanzee. RESULTS: In this study, we analyzed to find molecular characteristics of human brain functions from the difference of transcriptome between human and chimpanzee's brain using the functional module-centric co expression analysis. We performed analysis of brain disease association and systems-level connectivity of species-specific co-expressed functional modules. CONCLUSIONS: Throughout the analyses, we found human-specific functional modules and significant overlap between their genes in known brain disease genes, suggesting that human brain disorder could be mediated by the perturbation of modular activities emerged in human brain specialization. In addition, the human specific modules having neurobiological functions exhibited higher networking than other functional modules. This finding suggests that the expression of neural functions are more connected than other functions, and the resulting high order brain functions could be identified as a result of consolidated inter modular gene activities. Our result also showed that the functional module based transcriptome analysis has a potential to expand molecular understanding of high order complex functions like cognitive abilities and brain disorders. PMID- 26671688 TI - Intramural metastasis of T1 rectal cancer: report of a case report. AB - BACKGROUND: Intramural metastasis (IM) is extremely rare in colorectal cancer, although it often occurred in esophageal cancer. CASE PRESENTATION: We report a rare case of T1 rectal cancer with IM which was successfully resected by laparoscopic surgery. A 62-year-old man was admitted to our institution for the treatment of rectal cancer detected by medical examination. Colonoscopy revealed two tumors in the rectum: a type II rectal cancer of 2 cm in diameter located 5 cm proximal to the anal verge and a submucosal tumor of 1 cm in diameter located approximately 1.5 cm proximal to the rectal cancer. Abdominal computed tomography (CT), magnetic resonance imaging (MRI), and transrectal ultrasonography indicated the rectal cancer invaded into the submucosal layer with no metastasis to regional lymph nodes or distant organs. The patient underwent laparoscopic intersphincteric resection.Histopathological analysis revealed that the rectal cancer was moderately differentiated adenocarcinoma (stage I; pT1N0M0 according to the 7th edition of UICC) with severe lymphovascular invasion (ly1, v3) and that the submucosal tumor was composed of moderately differentiated adenocarcinoma proliferating within the muscularis propria. A number of features of the submucosal tumor indicated that this was an IM of the rectal cancer: clearly distinct location from the rectal cancer, growth predominantly within the muscularis propria, similar structural and cellular heterogeneity, and the presence of tumor emboli within vascular vessels. The patient was postoperatively followed for more than 4 years without any sign of recurrence. CONCLUSIONS: To the best of our knowledge, this is the first report of the T1 rectal cancer with IM. PMID- 26671690 TI - A case of double vision. PMID- 26671689 TI - In vitro optical quality comparison between the Mini WELL Ready progressive multifocal and the TECNIS Symfony. AB - PURPOSE: To compare the optical quality between two intraocular lenses (IOLs): the Mini WELL Ready progressive multifocal (SIFI Medtech, Catania, Italy), and the TECNIS Symfony (Abbott Laboratories, Illinois, USA), which both provide a continuous range of vision from far to near positions. METHODS: The in vitro optical quality of each lens was assessed with an instrument conceived for measuring the modulation transfer function (MTF). The optical quality of each lens was described in terms of MTF, through-focus MTF, defocus tolerance, pupil dependence, and Strehl ratio MTF. These metrics were assessed for the best lens far focus, and at four vergences (from -1.5 to -3.0 D in 0.5-D steps), at 3.0 and 4.5 mm apertures. RESULTS: The through-focus curves of each lens showed two main areas: one corresponding to far-distance vision, and another to intermediate- and near-distance vision. Both lenses showed similar MTF curves and Strehl ratio values at both apertures. The optical quality of both lenses slightly decreased with the aperture for all vergences. Nevertheless, the quality of the progressive multifocal lens increased with the aperture at far-distance vision. This lens also showed the largest defocus tolerance at near-distance vision for both apertures. CONCLUSIONS: The results obtained in the present study suggest that both designs might enlarge the depth of focus. Whereas, the Mini WELL Ready showed better optical quality than the TECNIS Symfony at far vision with 4.5 mm aperture, and larger defocus tolerance than the diffractive lens at near-distance vision. PMID- 26671698 TI - Interest in mental health care among patients making eVisits. AB - OBJECTIVES: The Internet allows patients opportunities for eVisits, in which a patient communicates electronically with a clinician who then makes a diagnosis and treatment recommendations. The status of mental health eVisits in these systems is still evolving. We examined features of mental health eVisits in a patient portal that did not explicitly provide an option for such care. STUDY DESIGN: Retrospective review of patient portal use. METHODS: Between April 2009 and mid-June 2012, over 2000 patients completed a total of 3601 eVisits through a patient portal at the University of Pittsburgh Medical Center. Although eVisits for mental health conditions were not explicitly offered, patients could choose an "other" option for the eVisit. We tracked diagnoses given by physicians in these "other" eVisits using Clinical Classification Software developed in the Healthcare Cost and Utilization Project. RESULTS: Of 685 patients choosing the "other" option for their eVisit (23.9% of patients making eVisits), 13.4% received mental health diagnoses, primarily anxiety and depression disorders. These patients represented 4% of all patients making eVisits. They were younger (41.1 +/- 12.4 vs 46.2 +/- 13.2; P < .001) and more likely to be female (82.6% vs 71.1%; P = .017) than patients not receiving mental health diagnoses. It took physicians longer to respond to mental health eVisits (same day in 71% of diagnoses involving mental health but 79.0% in all other diagnoses, P = .054). CONCLUSIONS: Patients are interested in eVisits for mental health care. Protocols that allow prompt attention to common mental health concerns in eVisits may be needed. PMID- 26671700 TI - Health IT-assisted population-based preventive cancer screening: a cost analysis. AB - OBJECTIVES: Novel health information technology (IT)-based strategies harnessing patient registry data seek to improve care at a population level. We analyzed costs from a randomized trial of 2 health IT strategies to improve cancer screening compared with usual care from the perspective of a primary care network. STUDY DESIGN: Monte Carlo simulations were used to compare costs across management strategies. METHODS: We assessed the cost of the software, materials, and personnel for baseline usual care (BUC) compared with augmented usual care (AUC [ie, automated patient outreach]) and augmented usual care with physician input (AUCPI [ie, outreach mediated by physicians' knowledge of their patient panels]) over 1 year. RESULTS: AUC and AUCPI each reduced the time physicians spent on cancer screening by 6.5 minutes per half-day clinical session compared with BUC without changing cancer screening rates. Assuming the value of this time accrues to the network, total costs of cancer screening efforts over the study year were $3.83 million for AUC, $3.88 million for AUCPI, and $4.10 million for BUC. AUC was cost-saving relative to BUC in 87.1% of simulations. AUCPI was cost saving relative to BUC in 82.5% of simulations. Ongoing per patient costs were lower for both AUC ($35.63) and AUCPI ($35.58) relative to BUC ($39.51). CONCLUSIONS: Over the course of the study year, the value of reduced physician time devoted to preventive cancer screening outweighed the costs of the interventions. Primary care networks considering similar interventions will need to capture adequate physician time savings to offset the costs of expanding IT infrastructure. PMID- 26671699 TI - The impact of electronic health records and teamwork on diabetes care quality. AB - OBJECTIVES: Evidence of the impact electronic health records (EHRs) have on clinical outcomes remains mixed. The impact of EHRs likely depends on the organizational context in which they are used. This study focuses on one aspect of the organizational context: cohesion of primary care teams. We examined whether team cohesion among primary care team members changed the association between EHR use and changes in clinical outcomes for patients with diabetes. STUDY DESIGN: Retrospective longitudinal study. METHODS: We combined provider reported primary care team cohesion with lab values for patients with diabetes collected during the staggered EHR implementation (2005-2009). We used multivariate regression models with patient-level fixed effects to assess whether team cohesion levels changed the association between outpatient EHR use and clinical outcomes for patients with diabetes. Subjects were comprised of 80,611 patients with diabetes, in whom we measured changes in glycated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C). RESULTS: For A1C, EHR use was associated with an average decrease of 0.11% for patients with higher-cohesion primary care teams compared with a decrease of 0.08% for patients with lower cohesion teams (difference = 0.02% in A1C; 95% CI, 0.01%-0.03%). For LDL-C, EHR use was associated with a decrease of 2.15 mg/dL for patients with higher cohesion primary care teams compared with a decrease of 1.42 mg/dL for patients with lower-cohesion teams (difference = 0.73 mg/dL; 95% CI, 0.41-1.11 mg/dL). CONCLUSIONS: Patients cared for by higher cohesion primary care teams experienced modest but statistically significantly greater EHR-related health outcome improvements, compared with patients cared for by providers practicing in lower cohesion teams. PMID- 26671701 TI - EHR adoption among ambulatory care teams. AB - OBJECTIVES: This study provides information on the types of practices that employ 2 types of advance practice providers (APPs), nurse practitioners (NPs) and physician assistants (PAs), and the association between employment of APPs and health information technology (IT) adoption by the practice. STUDY DESIGN: Three outcomes predicted the likelihood that practices employed at least 1 NP, at least 1 PA, or at least 1 of either type of APP; one outcome estimated electronic health record (EHR) adoption across practices; and 4 models assessed the EHR functionalities used by practices. METHODS: Data from SK and A Information Services' 2013 Office-Based Provider Database were used to estimate EHR adoption using a Poisson regression model. Independent variables included practice size, care setting, practice specialty, ownership, geographic region, whether a practice employed a NP, and whether a practice employed a PA. RESULTS: In 2013, three-fourths of practices that employed at least 1 APP had adopted an EHR. Practices that employed at least 1 APP were 9% to 12% more likely to have an EHR that had advanced functionalities, compared with practices without an APP. CONCLUSIONS: This study found an association between employment of APP staff and practice-level adoption of EHRs and practice-level adoption of certain EHR functionalities. Practices that employ APPs are prepared to implement team-based approaches to care that may be further enhanced through the use of health IT. Future research should examine how practices with APPs are using health IT to promote better health and coordinate care. PMID- 26671702 TI - Preventing patient absenteeism: validation of a predictive overbooking model. AB - OBJECTIVES: To develop a model that identifies patients at high risk for missing scheduled appointments ("no-shows" and cancellations) and to project the impact of predictive overbooking in a gastrointestinal endoscopy clinic-an exemplar resource-intensive environment with a high no-show rate. STUDY DESIGN: We retrospectively developed an algorithm that uses electronic health record (EHR) data to identify patients who do not show up to their appointments. Next, we prospectively validated the algorithm at a Veterans Administration healthcare network clinic. METHODS: We constructed a multivariable logistic regression model that assigned a no-show risk score optimized by receiver operating characteristic curve analysis. Based on these scores, we created a calendar of projected open slots to offer to patients and compared the daily performance of predictive overbooking with fixed overbooking and typical "1 patient, 1 slot" scheduling. RESULTS: Data from 1392 patients identified several predictors of no-show, including previous absenteeism, comorbid disease burden, and current diagnoses of mood and substance use disorders. The model correctly classified most patients during the development (area under the curve [AUC] = 0.80) and validation phases (AUC = 0.75). Prospective testing in 1197 patients found that predictive overbooking averaged 0.51 unused appointments per day versus 6.18 for typical booking (difference = -5.67; 95% CI, -6.48 to -4.87; P < .0001). Predictive overbooking could have increased service utilization from 62% to 97% of capacity, with only rare clinic overflows. CONCLUSIONS: Information from EHRs can accurately predict whether patients will no-show. This method can be used to overbook appointments, thereby maximizing service utilization while staying within clinic capacity. PMID- 26671703 TI - A health systems improvement research agenda for AJMC's next decade. PMID- 26671704 TI - Art on the Nanoscale and Beyond. AB - Methods of forming and patterning materials at the nano- and microscales are finding increased use as a medium of artistic expression, and as a vehicle for communicating scientific advances to a broader audience. While sharing many attributes of other art forms, miniaturized art enables the direct engagement of sensory aspects such as sight and touch for materials and structures that are otherwise invisible to the eye. The historical uses of nano-/microscale materials and imaging techniques in arts and sciences are presented. The motivations to create artwork at small scales are discussed, and representations in scientific literature and exhibitions are explored. Examples are presented using semiconductors, microfluidics, and nanomaterials as the artistic media; these utilized techniques including micromachining, focused ion beam milling, two photon polymerization, and bottom-up nanostructure growth. Finally, the technological factors that limit the implementation of artwork at miniature scales are identified, and potential future directions are discussed. As research marches toward even smaller length scales, innovative and engaging visualizations and artistic endeavors will have growing implications on education, communication, policy making, media activism, and public perception of science and technology. PMID- 26671705 TI - Healthcare service utilisation costs attributable to rheumatoid arthritis in France: Analysis of a representative national claims database. AB - OBJECTIVE: To estimate healthcare service utilisation costs of patients with rheumatoid arthritis in France and to estimate the fraction of these costs attributable to RA. METHOD: The "Echantillon generaliste des beneficiaires" (EGB) is a 1/97 random sample of the main national claims database covering the French population. A cohort of patients with rheumatoid arthritis was constituted of all adults benefiting from full coverage for rheumatoid arthritis (ICD-10 M05-06) on 1st january 2009. A control group matched for age and gender was identified. Health expenditures were assessed from the payer's perspective for the year 2010. RESULTS: The annual per capita reimbursed total health expenditure was ?6,404 in 2010, an amount around two times higher than in the control group ?3,095 (P<0.0001). The main contributors to this extra cost were outpatient care (+?2,407; 72.7%), including medication (+?1,686; 50.0%), and inpatient care (+?903; 27.3%). Patients treated by biological agents generated an age-adjusted per capita annual expenditure about three times higher than untreated patients (?15,757 versus ?4,640). CONCLUSION: Only half of medical expenditure by patients with rheumatoid arthritis is attributable to their disease and use of biological agents has become a major driver of cost. PMID- 26671706 TI - Liver Transplant in a Patient With Acquired Epidermolysis Bullosa and Associated End-Stage Liver Disease. AB - We report the first case of a liver transplant in a patient with epidermolysis bullosa acquisita and associated hepatitis B virus-hepatitis D virus cirrhosis and its inherent technical issues. Epidermolysis bullosa acquisita is an autoimmune multisystem disorder involving skin and mucosa characterized by the appearing of blisters and erosions. The more severe forms may result in nutritional compromise, anemia, osteopenia, dilated cardiomyopathy, laryngeal mucosal involvement, esophageal strictures, bladder, and kidney involvement requiring surgical intervention. Epidermolysis bullosa acquisita has become recognized as a multisystem disorder that poses several surgical challenges. This case shows that liver transplant is a feasible procedure in patients affected by epidermolysis bullosa acquisita. Patients with epidermolysis bullosa acquisita require a particular pretransplant assessment and a dedicated intra- and postoperative management of every invasive procedure that can traumatize the skin and mucosal epithelium to achieve an uneventful liver transplant. Epidermolysis bullosa acquisita does not represent a contraindication to liver transplant, and immunosuppression after transplant may favor a good systemic control of this immunologic disorder. PMID- 26671707 TI - Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System. AB - CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition during CRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S. pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems. PMID- 26671708 TI - Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors. AB - A wide variety of pathogens targets chemokine signaling networks in order to disrupt host immune surveillance and defense. Here, we report a structural and mutational analysis of rodent herpesvirus Peru encoded R17, a potent chemokine inhibitor that sequesters CC and C chemokines with high affinity. R17 consists of a pair of beta-sandwich domains linked together by a bridging sheet, which form an acidic binding cleft for the chemokine CCL3 on the opposite face of a basic surface cluster that binds glycosaminoglycans. R17 promiscuously engages chemokines primarily through the same N-loop determinants used for host receptor recognition while residues located in the chemokine 40s loop drive kinetically stable complex formation. The core fold adopted by R17 is unexpectedly similar to that of the M3 chemokine decoy receptor encoded by MHV-68, although, strikingly, neither the location of ligand engagement nor the stoichiometry of binding is conserved, suggesting that their functions evolved independently. PMID- 26671709 TI - The Structural Basis for Lipid and Endotoxin Binding in RP105-MD-1, and Consequences for Regulation of Host Lipopolysaccharide Sensitivity. AB - MD-1 is a member of the MD-2-related lipid-recognition (ML) family, and associates with RP105, a cell-surface protein that resembles Toll-like receptor 4 (TLR4). The RP105?MD-1 complex has been proposed to play a role in fine-tuning the innate immune response to endotoxin such as bacterial lipopolysaccharide (LPS) via TLR4?MD-2, but controversy surrounds its mechanism. We have used atomically detailed simulations to reveal the structural basis for ligand binding and consequent functional dynamics of MD-1 and the RP105 complex. We rationalize reports of endogenous phospholipid binding, by showing that they prevent collapse of the malleable MD-1 fold, before refining crystallographic models and uncovering likely binding modes for LPS analogs. Subsequent binding affinity calculations reveal that endotoxin specificity arises from the entropic cost of expanding the MD-1 cavity to accommodate bulky lipid tails, and support the role of MD-1 as a "sink" that sequesters endotoxin from TLR4 and stabilizes RP105/TLR4 interactions. PMID- 26671710 TI - Electrocortical Dynamics in Children with a Language-Learning Impairment Before and After Audiovisual Training. AB - Detecting and discriminating subtle and rapid sound changes in the speech environment is a fundamental prerequisite of language processing, and deficits in this ability have frequently been observed in individuals with language-learning impairments (LLI). One approach to studying associations between dysfunctional auditory dynamics and LLI, is to implement a training protocol tapping into this potential while quantifying pre- and post-intervention status. Event-related potentials (ERPs) are highly sensitive to the brain correlates of these dynamic changes and are therefore ideally suited for examining hypotheses regarding dysfunctional auditory processes. In this study, ERP measurements to rapid tone sequences (standard and deviant tone pairs) along with behavioral language testing were performed in 6- to 9-year-old LLI children (n = 21) before and after audiovisual training. A non-treatment group of children with typical language development (n = 12) was also assessed twice at a comparable time interval. The results indicated that the LLI group exhibited considerable gains on standardized measures of language. In terms of ERPs, we found evidence of changes in the LLI group specifically at the level of the P2 component, later than 250 ms after the onset of the second stimulus in the deviant tone pair. These changes suggested enhanced discrimination of deviant from standard tone sequences in widespread cortices, in LLI children after training. PMID- 26671711 TI - Perceived physical competence towards physical activity, and motivation and enjoyment in physical education as longitudinal predictors of adolescents' self reported physical activity. AB - OBJECTIVES: The aim of the study was to investigate if adolescents' perceived physical competence towards physical activity (PA), and autonomous motivation and enjoyment in physical education (PE) during early adolescence can predict amount and intensity of self-reported physical activity six years later. DESIGN: This study utilized a 6-year longitudinal data set collected within Finnish school settings. Students responded to questionnaires measuring their perceived physical competence towards physical activity, and autonomous motivation and enjoyment in PE during their first year at middle school (Grade 7), and their PA engagement during their last year in high school (Grade 12). METHODS: A sample of 333 students (200 girls, 133 boys; M age=12.41, years, SD=.27) participated in the study. Perceived physical competence in physical activity was assessed by the sport competence dimension of the Physical Self-Perception Profile, autonomous motivation in PE was assessed by the Sport Motivation Scale and enjoyment in PE by the Sport Enjoyment Scale. Students' self-reported metabolic equivalent (MET) and PA intensity (light [LPA], moderate [MPA], vigorous [VPA]) was calculated from the short form of International Physical Activity Questionnaire. RESULTS: Perceived physical competence towards physical activity significantly predicted total METs (beta=.28), MPA (beta=.18) and VPA (beta=.29) six years later. Autonomous motivation and enjoyment in PE at Grade 7, however, were not significant predictors of later PA. CONCLUSIONS: The results of this study support the proposition that self-perception of an individual's abilities arising from interactions with the environment related to PA during early puberty has an influential effect on later PA behaviour. PMID- 26671712 TI - The Simbla TURBT Simulator in Urological Residency Training: From Needs Analysis to Validation. AB - OBJECTIVE: To investigate the value of the physical Simbla Transurethral Resection of a Bladder Tumor (TURBT) simulator as an educational tool within urological residency training, by means of a training needs analysis (TNA) and assessment of its feasibility, acceptability, and face, content, and construct validity. METHODS: To analyze the training needs for TURBT, procedural steps and pitfalls were identified and the TNA was completed during an expert consensus meeting. Participants (n = 76) were divided into three groups based on their experience in TURBT: novices, intermediates, and experts. Participants performed two standardized TURBT procedures on the simulator. Face validity and content validity, as well as feasibility and acceptability, were assessed with a quantitative survey. Construct validity was assessed by comparing the performance of novices, intermediates, and experts on resection time, quality of tumor resection, and overall performance. RESULTS: Of the 21 procedural steps and 17 pitfalls defined in TNA, 13 steps and 8 pitfalls were covered by the Simbla. Participants rated the Simbla's overall realism (face validity) with a score of 8 of 10 (range 6-9). The simulator was judged to be most useful (content validity) for learning eye-hand coordination: score 8 (6-10). All aspects regarding realism and usefulness were rated above the acceptability threshold of 6/10. Intermediates (100%) and experts (96%) considered the Simbla to be a useful educational tool within the urological curriculum. Resection time was longer for novices than for experts (p < 0.05; construct validity). In addition, the overall performance of novices was rated lower compared with intermediates and experts, and novices showed more irradical resections and bladder perforations (all p < 0.05). CONCLUSIONS: The Simbla TURBT simulator is a valid, feasible, and acceptable educational tool for training procedural skills and may be implemented in the urological curriculum to complement learning in clinical practice. TNA is valuable in defining training objectives and evaluating the educational value of a simulator. PMID- 26671716 TI - The value of multimodality intraoperative neurophysiological monitoring in treating pediatric Chiari malformation type I. AB - INTRODUCTION: Chiari malformation type I is defined as a descent of cerebellar tonsils below the level of the foramen magnum. The traditional treatment for symptomatic patients is foramen magnum decompression (FMD) surgery. Intraoperative neurophysiological monitoring (INM) is an established surgical adjunct, which is proposed to reduce the potential risk of various surgical procedures. Though INM has been suggested as being helpful in patient positioning and in determining the optimal surgical extent of FMD (i.e., duroplasty, laminectomy, tonsillectomy), its shortcomings include prolongation of anesthesia and surgery as well as monetary costs. Multimodality INM including transcranial electric motor evoked potential (TcMEP) is not routinely employed in most practices. This study evaluates efficacy of multimodality INM during FMD. METHODS: This work is a retrospective analysis of prospectively collected data. Twenty-two FMD surgeries in 21 pediatric patients (aged 1-18 years) were performed at our center utilizing multimodality INM. All patients presented Chiari malformation type I, 18 of which had presented with syringomyelia, underwent posterior fossa decompression (FMD + C1 laminectomy), accompanied in some with additional cervical laminectomies, duroplasty, and partial tonsillectomies. TcMEP and somatosensory evoked potentials (SSEP) were monitored throughout the procedure including before and after positioning. INM alarms were correlated with perioperative and long-term patient outcomes. RESULTS: INM data remained stable during 19 operations. Three cases displayed significant attenuation in the monitoring signals, all concomitant with patient positioning on the surgical table. One case showed attenuation in SSEP data only, which remained attenuated following repositioning. Another displayed altered TcMEP concomitant with positioning which partially stabilized following repositioning and resolved following bony decompression. The third case showed unilateral attenuation of both TcMEP and SSEP data, which did not rectify until closure. In each of these three cases, no new neurological deficits were observed post operatively. CONCLUSIONS: Multimodality INM can be useful in FMD surgery, particularly during patient positioning. TcMEP attenuations may occur independent of SSEPs. The clinical implications of these monitoring alerts have yet to be defined. There is a need to establish an optimal, cost-effective monitoring protocol for FMD. PMID- 26671715 TI - A radiologic and anatomic study of the superior semicircular canal. AB - OBJECTIVES: The present study sought to determine whether there is a correlation between the prevalence of superior semicircular canal (SSC) dehiscence (SSCD) on temporal CT and population age. The secondary objective was to identify anatomic factors for SSCD by studying SSC diameter and its protrusion into the middle cranial fossa. The aim was to determine the acquired or congenital origin of SSCD (Minor's syndrome). MATERIAL AND METHOD: A single-center retrospective radiological and anatomic study included 180 CT scans of 354 petrous parts of the temporal bone taken between January and December 2011 in a university hospital center. Bone thickness above the SSC was measured and classified in 4 grades: grade 1, >2.5mm; grade 2, <2.5mm: grade 3, predehiscent; grade 4, dehiscent. SSC diameter was also measured, as was the height of SSC protrusion into the middle cranial fossa. RESULTS: SSCD was found in 0.8% of cases and predehiscence in 12%. Patients with dehiscence were older; patients with grade 3 or 4 were significantly older than those free of dehiscence (P<0.05). There was no significant difference in SSC diameter according to grade. In grade 1, protrusion was greater than in other subjects, with a significant correlation between age and reduced protrusion (P<0.05). CONCLUSION: The study demonstrated a correlation between aging and SSCD prevalence. Reduced SSC roof height with age suggests that SSCD may be an acquired phenomenon, related in some way to aging of the base of the skull. PMID- 26671717 TI - Multilayered electrospun fibrous meshes for restenosis-suppressing metallic stents. AB - Nanofiber is a flexible and highly porous mesh that is advantageous for coating bare metal stent and local drug delivery. Herein, we developed drug-eluting stent coated with PCL/PU blending coaxial nanofiber for controlling drug release manner and suppressing in-stent restenosis, which is a representative side effect of stenting surgery. The shell of coaxial electrospun nanofibrous are composed of poly (epsilon-caprolactone) (PCL) and polyurethane (PU) for biodegradability and elasticity to the polymeric coating of stent. Paclitaxel (PTX) is loaded into both the core and shell through electrospinning using coaxial nozzle with different weight ratio. The morphology of nanofiber-coated stent, expansion state, and core/shell structure of nanofiber were visualized by scanning electron microscope and transmission electron microscope. As more amount of PCL/PU was infused from the outer nozzle, PTX release speed from the nanofiber was increased. And PTX suppressed L6 cell proliferation in vitro expecting potential possibility of PTX-loaded coaxial nanofiber as a drug-eluting stent coating material. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 628-635, 2017. PMID- 26671720 TI - Rapid determination of residues of pesticides in honey by uGC-ECD and GC-MS/MS: Method validation and estimation of measurement uncertainty according to document No. SANCO/12571/2013. AB - A simple and straightforward method for simultaneous determination of residues of 13 pesticides in honey samples (acrinathrin, bifenthrin, bromopropylate, cyhalothrin-lambda, cypermethrin, chlorfenvinphos, chlorpyrifos, coumaphos, deltamethrin, fluvalinate-tau, malathion, permethrin and tetradifon) from different pesticide classes has been developed and validated. The analytical method provides dissolution of honey in water and an extraction of pesticide residues by n-Hexane followed by clean-up on a Florisil SPE column. The extract was evaporated and taken up by a solution of an injection internal standard (I IS), ethion, and finally analyzed by capillary gas chromatography with electron capture detection (GC-uECD). Identification for qualitative purpose was conducted by gas chromatography with triple quadrupole mass spectrometer (GC-MS/MS). A matrix-matched calibration curve was performed for quantitative purposes by plotting the area ratio (analyte/I-IS) against concentration using a GC-uECD instrument. According to document No. SANCO/12571/2013, the method was validated by testing the following parameters: linearity, matrix effect, specificity, precision, trueness (bias) and measurement uncertainty. The analytical process was validated analyzing blank honey samples spiked at levels equal to and greater than 0.010 mg/kg (limit of quantification). All parameters were satisfactorily compared with the values established by document No. SANCO/12571/2013. The analytical performance was verified by participating in eight multi-residue proficiency tests organized by BIPEA, obtaining satisfactory z-scores in all 70 determinations. Measurement uncertainty was estimated according to the top-down approaches described in Appendix C of the SANCO document using the within laboratory reproducibility relative standard deviation combined with laboratory bias using the proficiency test data. PMID- 26671721 TI - Evaluation of a Kinematically-Driven Finite Element Footstrike Model. AB - A dynamic finite element model of a shod running footstrike was developed and driven with 6 degree of freedom foot segment kinematics determined from a motion capture running trial. Quadratic tetrahedral elements were used to mesh the footwear components with material models determined from appropriate mechanical tests. Model outputs were compared with experimental high-speed video (HSV) footage, vertical ground reaction force (GRF), and center of pressure (COP) excursion to determine whether such an approach is appropriate for the development of athletic footwear. Although unquantified, good visual agreement to the HSV footage was observed but significant discrepancies were found between the model and experimental GRF and COP readings (9% and 61% of model readings outside of the mean experimental reading +/- 2 standard deviations, respectively). Model output was also found to be highly sensitive to input kinematics with a 120% increase in maximum GRF observed when translating the force platform 2 mm vertically. While representing an alternative approach to existing dynamic finite element footstrike models, loading highly representative of an experimental trial was not found to be achievable when employing exclusively kinematic boundary conditions. This significantly limits the usefulness of employing such an approach in the footwear development process. PMID- 26671722 TI - Hierarchical Self-Assembly of a Renewable Nanosized Pentacyclic Dihydroxy triterpenoid Betulin Yielding Flower-Like Architectures. AB - Betulin, a naturally occurring 6-6-6-6-5 pentacyclic dihydroxy-triterpenoid, is extractable from the bark of white birch (Betula papyrifera). We report the first self-assembly properties of betulin in different liquids. The molecule spontaneously self-assembled in different media, yielding flower-like architectures of nano- to micrometers diameters via the formation of fibrillar networks. The self-assemblies have been characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, dynamic light scattering, FTIR, and X-ray diffraction studies. The porous microstructure of the self-assemblies has been utilized for the entrapment of fluorophore such as rhodamine-B and the anticancer drug doxorubicin. Moreover, the removal of toxic dyes such as rhodamine 6G, crystal violet, methylene blue, and cresol red has also been demonstrated. PMID- 26671723 TI - Neuroprotection: Basic mechanisms and translational potential. PMID- 26671724 TI - Ionophore silica-coated magnetite nanoparticles as a recyclable heterogeneous catalyst for one-pot green synthesis of 2,4,5-trisubstituted imidazoles. AB - Novel multi-SO3H functionalized strong Bronsted acidic ionic liquid coated magnetite nanoparticles have been prepared and applied as catalyst for the synthesis of 2,4,5-trisubstituted imidazoles. The results showed that a novel catalyst was very efficient for the reaction and could be magnetically separated and reused at least 6 times with less reduction in its catalytic activity. Operational simplicity, low cost of the catalyst used, high yields, environmental friendliness, wide applicability, reusability and easy recovery of the catalyst using an external magnet are the most important features of this methodology. The catalyst was characterized by Fourier transform infrared spectroscopy (FT-IR), X Ray diffraction analysis (XRD), field emission scanning electron microscopy (FE SEM), energy dispersive X-ray analysis (EDX), dynamic laser scattering (DLS) and vibrating sample magnetometry (VSM). PMID- 26671726 TI - The Importance Presence and the Number of Leads with Fragmented QRS in Coronary Artery Disease. PMID- 26671725 TI - Toxic tau oligomer formation blocked by capping of cysteine residues with 1,2 dihydroxybenzene groups. AB - Neurofibrillary tangles, composed of hyperphosphorylated tau fibrils, are a pathological hallmark of Alzheimer's disease; the neurofibrillary tangle load correlates strongly with clinical progression of the disease. A growing body of evidence indicates that tau oligomer formation precedes the appearance of neurofibrillary tangles and contributes to neuronal loss. Here we show that tau oligomer formation can be inhibited by compounds whose chemical backbone includes 1,2-dihydroxybenzene. Specifically, we demonstrate that 1,2-dihydroxybenzene containing compounds bind to and cap cysteine residues of tau and prevent its aggregation by hindering interactions between tau molecules. Further, we show that orally administered DL-isoproterenol, an adrenergic receptor agonist whose skeleton includes 1,2-dihydroxybenzene and which penetrates the brain, reduces the levels of detergent-insoluble tau, neuronal loss and reverses neurofibrillary tangle-associated brain dysfunction. Thus, compounds that target the cysteine residues of tau may prove useful in halting the progression of Alzheimer's disease and other tauopathies. PMID- 26671727 TI - IL-1beta mediating high mobility group box protein-1 expression in condylar chondrocyte during temporomandibular joint inflammation. AB - BACKGROUND: Temporomandibular joint (TMJ) osteoarthritis(OA)characterized with cartilage degen-eration is associated with inflammation. High mobility group box chromosomal protein-1(HMGB-1)is a potent mediator of inflammation and the trigger of OA. The expression of HMGB-1 in TMJ OA was uncovered, but the role of HMGB-1 in TMJ cartilage degeneration is not fully understood. In this study, the regulation of HMGB-1 in TMJ condylar cartilage was revealed. METHODS: A complete Freund's adjuvant (CFA)-induced TMJ inflammation animal model was employed and the expression of HMGB-1 was detected at 1st, 2nd, and 6th weeks by immunohistochemistry. TMJ condylar chondrocytes were incubated with IL-1beta (10 and 40 ng/ml) at 24, 48, and 72 h, and the translocation and protein level of HMGB-1 were evaluated by immunofluorescence and Western blot. RESULT: Nuclear HMGB-1 staining was predominantly located in chondrocytes of both the fibrosis and proliferative zones in healthy TMJ. 1st week and 2nd week after CFA injection, immunoreaction could be detected in the cytoplasms of HMGB-1-positive cells and cartilage matrix especially in hypertrophic zone. At 6th week after CFA injection, cartilage matrix expression was disappeared and the cytoplasm expression of HMGB-1 was very weak in hypertrophic zone. HMGB-1 was translocated from the nucleus to the cytoplasm at 48 h after incubated with IL-1beta (10 ng/ml and 40 ng/ml). The protein level of HMGB-1 was increased after stimulation and had a peak at 48 h. CONCLUSION: HMGB-1 might be associated with TMJ inflammation and OA. Insight into the role of HMGB-1 in TMJ inflammation is helpful to add the new knowledge into the pathogenesis of TMJ OA. PMID- 26671728 TI - Possible Antipruritic Mechanism of Cyclosporine A in Atopic Dermatitis. AB - Cyclosporine A is an immunosuppressive agent that suppresses pruritus and is currently used in the treatment of patients with severe atopic dermatitis. The aim of this study was to elucidate the antipruritic mechanism of cyclosporine A using a mouse model of atopic dermatitis. Intraperitoneal injection of cyclosporine A (5 mg/kg) significantly reduced epidermal nerve density, number of scratching bouts, dermatitis scores, and transepidermal water loss, as well as decreasing the numbers of inflammatory cells in the dermis and decreasing epidermal thickness. Intraperitoneal injection of cyclosporine A dose-dependently inhibited increased itch-related receptor gene expression, such as interleukin-31 receptor A and neurokinin-1 receptor, in the dorsal root ganglion of atopic dermatitis model mice. Thus, the antipruritic efficacy of cyclosporine A may involve reduced epidermal nerve density and expression levels of itch-related receptor genes in the dorsal root ganglion, as well as improvement in acanthosis and reduction in cutaneous inflammatory cell number. PMID- 26671730 TI - N-Alkyl Ammonium Resorcinarene Salts as High-Affinity Tetravalent Chloride Receptors. AB - N-Alkyl ammonium resorcinarene salts (NARYs, Y=triflate, picrate, nitrate, trifluoroacetates and NARBr) as tetravalent receptors, are shown to have a strong affinity for chlorides. The high affinity for chlorides was confirmed from a multitude of exchange experiments in solution (NMR and UV/Vis), gas phase (mass spectrometry), and solid-state (X-ray crystallography). A new tetra-iodide resorcinarene salt (NARI) was isolated and fully characterized from exchange experiments in the solid-state. Competition experiments with a known monovalent bis-urea receptor (5) with strong affinity for chloride, reveals these receptors to have a much higher affinity for the first two chlorides, a similar affinity as 5 for the third chloride, and lower affinity for the fourth chloride. The receptors affinity toward chloride follows the trend K1 ?K2 ?K3 ~5>K4, with Ka =5011 m(-1) for 5 in 9:1 CDCl3/[D6]DMSO. PMID- 26671729 TI - Selective bronchial intubation in patient with tracheobronchial alterations. PMID- 26671731 TI - The potential diagnostic power of extracellular vesicle analysis for multiple myeloma. AB - Multiple myeloma (MM) is a hematologic malignancy of plasma cells (PCs). In the United States, MM accounts for approximately 1% of all diagnoses and 2% of all cancer-related deaths. Although MM is a treatable disease, most patients eventually relapse, and despite the development of numerous treatment options it is still considered incurable. Mechanisms of communication between MM-PCs and bone marrow microenvironment, including cell-cell contacts and release of pro survival factors, promote cancer cell survival and drug resistance. Recently, the importance of extracellular vesicles (EVs) as mechanisms of communication between MM cells and other cells in the microenvironment has been reported. In this review, the authors provide the update on the biology and clinical aspects of EVs in MM. PMID- 26671732 TI - Distribution and population structure of the anther smut Microbotryum silenes acaulis parasitizing an arctic-alpine plant. AB - Cold-adapted organisms with current arctic-alpine distributions have persisted during the last glaciation in multiple ice-free refugia, leaving footprints in their population structure that contrast with temperate plants and animals. However, pathogens that live within hosts having arctic-alpine distributions have been little studied. Here, we therefore investigated the geographical range and population structure of a fungus parasitizing an arctic-alpine plant. A total of 1437 herbarium specimens of the plant Silene acaulis were examined, and the anther smut pathogen Microbotryum silenes-acaulis was present throughout the host's geographical range. There was significantly greater incidence of anther smut disease in more northern latitudes and where the host locations were less dense, indicating a major influence of environmental factors and/or host demographic structure on the pathogen distribution. Genetic analyses with seven microsatellite markers on recent collections of 195 M. silenes-acaulis individuals revealed three main genetic clusters, in North America, northern Europe and southern Europe, likely corresponding to differentiation in distinct refugia during the last glaciation. The lower genetic diversity in northern Europe indicates postglacial recolonization northwards from southern refugia. This study combining herbarium surveys and population genetics thus uniquely reveals the effects of climate and environmental factors on a plant pathogen species with an arctic-alpine distribution. PMID- 26671733 TI - Semiconducting Group 15 Monolayers: A Broad Range of Band Gaps and High Carrier Mobilities. AB - Optoelectronic applications require materials both responsive to objective photons and able to transfer carriers, so new two-dimensional (2D) semiconductors with appropriate band gaps and high mobilities are highly desired. A broad range of band gaps and high mobilities of a 2D semiconductor family, composed of monolayer of Group 15 elements (phosphorene, arsenene, antimonene, bismuthene) is presented. The calculated binding energies and phonon band dispersions of 2D Group 15 allotropes exhibit thermodynamic stability. The energy band gaps of 2D semiconducting Group 15 monolayers cover a wide range from 0.36 to 2.62 eV, which are crucial for broadband photoresponse. Significantly, phosphorene, arsenene, and bismuthene possess carrier mobilities as high as several thousand cm(2) V( 1) s(-1) . Combining such broad band gaps and superior carrier mobilities, 2D Group 15 monolayers are promising candidates for nanoelectronics and optoelectronics. PMID- 26671734 TI - Treasure maps for cancer research: Online atlases are pairing tumor anatomy with gene activity to deliver rich troves of information. PMID- 26671735 TI - The evolving role of cytopathology in the era of advanced diagnostic and therapeutic bronchoscopy. PMID- 26671736 TI - Young investigator challenge: Application of cytologic techniques to circulating tumor cell specimens: Detecting activation of the oncogenic transcription factor STAT3. AB - BACKGROUND: The circulating tumor cell (CTC) field is rapidly advancing with the advent of continuously improving technologies for enriching these rare neoplastic cells from blood. CTC enumeration provides prognostic information, and CTC characterization has the potential to provide more useful information for the clinical decision-making process in this era of personalized medicine and targeted therapeutics. Proof-of-principle studies have shown that CTC samples can be characterized with a variety of techniques in the research laboratory environment. The goal of the current study was to validate routine cytologic techniques and immunohistochemical markers in CTC samples in a clinical cytology laboratory, using inducible phosphorylated signal transducer and activator of transcription 3 (pSTAT3) as a clinically important example and Ki-67 as a positive control. METHODS: Whole blood from noncancer patients was spiked with breast cancer cell lines with constitutive or inducible pSTAT3 expression and underwent CTC processing in the CellSearch system. The resulting CTC samples were subjected to various cytologic/immunocytochemical techniques and were compared with non-CTC-processed cultured cell controls. RESULTS: CTC-processed samples showed a morphology comparable to that of controls in cytospin, ThinPrep, and cell block preparations. Immunocytochemistry for Ki-67 and pSTAT3 provided biological information from CTC samples, showing uniform Ki-67 staining across all samples, pSTAT3 positivity in the constitutive and induced cells, and an absence of pSTAT3 expression in the noninduced cells, as expected. CONCLUSIONS: CTC samples can be processed in the cytology laboratory with routine methods. CTC morphologic and immunophenotypic analysis can be easily integrated into the existing clinical workflow, moving the field closer to a true peripheral blood liquid biopsy for cancer patients. PMID- 26671737 TI - Young investigator challenge: Cadherin-17 and SATB2 in cytology specimens: Do these new immunostains help in differentiating metastatic colorectal adenocarcinoma from adenocarcinomas of other origins? AB - BACKGROUND: Cadherin-17 (intestinal peptide-associated transporter) and SATB2 (SATB homeobox 2) immunoexpression has recently been described in surgical pathology to have value in establishing the colorectal origin of metastatic adenocarcinoma. However, to the authors' knowledge, the role of these markers in metastatic colorectal adenocarcinoma (MCA) in cytology has not been addressed to date. In the current study, the authors evaluated the contribution of cadherin-17 and SATB2 to the diagnosis of MCA in cytology specimens and compared these two novel markers with the standard gastrointestinal immunohistochemistry panel in an attempt to identify the optimal panel. METHODS: A total of 43 MCA cytology cases and 68 metastatic noncolorectal adenocarcinoma (non-MCA) cytology controls were stained for SATB2; cadherin-17; and the standard panel of cytokeratin (CK) 7, CK20, and Caudal-Type Homeobox Transcription Factor 2 (CDX2). Staining intensity and percentage of positive cells were recorded. Sensitivity and specificity values for immunostains individually and in combination were computed and compared. RESULTS: Despite specificities of 83.8% and 91.2%, respectively, for cadherin-17 and SATB2, when critically examining the new immunostains together with the standard panel, there was no significant difference noted with regard to prediction of MCA (vs non-MCA) compared with the standard panel alone (P < .6). CONCLUSIONS: The results of the current study reinforce that the standard gastrointestinal immunohistochemistry panel remains the gold standard for distinguishing MCA from non-MCA in cytology. PMID- 26671739 TI - 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, a polymethoxyflavone, exerts antitumor effect on PI3K/Akt signaling pathway in human gastric cancer cell BGC 7901. AB - 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), a polymethoxyflavone (PMF) mainly found in citrus plants, exhibits excellent physiological functions. In this study, we aimed to investigate the anticancer activity of 5HHMF against human gastric cancer cell BGC-7901 both in vitro and in vivo and illustrate the potential mechanisms. The proliferation of BGC-7901 cells was assessed by MTT assay. Reactive oxygen species (ROS) level was determined by ELISA kit. The protein expression was determined by western blot analysis. Antitumor activity of 5HHMF in vivo was evaluated in BALB/c nude mice. The results showed that treatment with 5HHMF significantly suppressed BGC-7901 cells proliferation, increased ROS generation, and upregulated cytochrome c release from the mitochondria to the cytosol. Western blot analysis demonstrated that 5HHMF significantly downregulated the expression of procaspase-3, procaspase-9, and PARP and upregulated cleaved caspase-3, cleaved caspase-9, cleaved PARP, and Bax/Bcl-2 ratio. Meanwhile, 5HHMF treatment markedly decreased the expression of PI3K and p-Akt. In addition, 5HHMF effectively inhibited tumor growth in xenograft models in BALB/c nude mice without major side action. In summary, 5HHMF induced apoptosis via targeting PI3K/Akt, indicating 5HHMF is a potential antitumor agent for gastric cancer. PMID- 26671740 TI - Rhombencephalitis due to Listeria monocytogenes: A Clinicopathologic Study of a Case. AB - INTRODUCTION: Central nervous system infections caused by Listeria monocytogenes usually manifest in the form of meningitis or meningoencephalitis, and are more common among immunosuppressed patients. Brainstem encephalitis (rhombencephalitis) is less common and fatal if not recognized and treated early. CASE REPORT: We describe the case of a 40-year-old, immunocompetent male patient, who presented with initial symptoms of high fever and productive cough. Signs of brainstem involvement appeared later. A magnetic resonance imaging of the brain revealed a lesion of inflammatory appearance in the right medulla oblongata, and the cerebrospinal fluid test showed mononuclear pleocytosis. Blood and cerebrospinal fluid cultures were negative. He presented with a significant improvement with the start of ceftriaxone and subsequent association of corticosteroids, until he developed respiratory failure and died. The third blood cultures grew after his death and they were positive for L. monocytogenes. An autopsy was carried out, which showed necrotizing inflammation, with gram positive bacilli in the brainstem and the cerebellum. CONCLUSIONS: A fatal delay in the diagnosis occurred, mainly because of the favorable clinical response to ceftriaxone and corticosteroids. This case reminds us that a febrile clinical presentation with brainstem involvement must generate the suspicion of a Listeria infection, and therefore ampicillin must be a part of the empirical treatment. PMID- 26671741 TI - Galactorrhea in a Patient With Aquaporin-4 Antibody-positive Neuromyelitis Optica Spectrum Disorder: A Case Report and Review of the Literature. AB - This is the first report of a case of galactorrhea in a patient with neuromyelitis optica spectrum disorder (NMOSD) diagnosed on the basis of antiaquaporin-4 antibody seropositivity. The hypothalamus is becoming known as an area highly expressing aquaporin-4 and frequently involved in intracranial lesions of patients with neuromyelitis optica (NMO). We reviewed cases of hypothalamic endocrinopathy among patients with NMO, NMOSD, and the Japanese opticospinal form of MS. Among these cases, galactorrhea was the second most common symptom. Signs of hypothalamic endocrinopathies may be obscured by the grave neurological deficits caused by NMO. We recommend paying special attention to hypothalamic endocrinopathies among patients with NMO or NMOSD, irrespective of brain MRI findings. PMID- 26671742 TI - Spinal Spot Sign. AB - INTRODUCTION: A marker predictive of hematoma expansion in the central nervous system could aid the selection of patients for hemostatic or surgical treatment. CASE REPORT: Here, we present a 83-year-old patient with acute spinal subdural hematoma with paraparesis progressing to paraplegia. A contrast extravasation within the intraspinal hematoma was visualized on spinal MR indicating active bleeding (spinal spot sign). A second acquisition of contrast-enhanced MR images showed progression of contrast extravasation helping to different active bleeding from spinal arteriovenous malformations/fistula. CONCLUSIONS: A "spinal spot sign" may be important for treatment decisions, notably in patients with incomplete neurological deficits at the time of imaging. PMID- 26671743 TI - Hypnic Headache and Basilar Artery Dolichoectasia. AB - BACKGROUND: Hypnic headache is regarded by most authors as a primary headache, but in some cases it was considered secondary to hypophysis, brain stem, or posterior fossa lesions. CASE: We report a case of a 69-year-old woman with a history of a headache that fulfils all International Classification of Headache Disorders-II criteria for hypnic headache, with 2 years of evolution, whose complementary investigation with magnetic resonance and magnetic resonance angiography revealed a dolichoectasia of the basilary artery. She was treated with verapamil with excellent response. CONCLUSIONS: To the best of our knowledge, this is the first described case of a patient with hypnic headache and a dolichoectasic basilar artery. The relation between these 2 entities is questionable, but we raise some possible explanations for this relationship. PMID- 26671744 TI - Cardiovascular Dysfunction in Multiple Sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) can affect cardiovascular function in a variety of ways leading to abnormalities in blood pressure response, heart rate, heart rhythm, left ventricular systolic function, and may cause pulmonary edema or cardiomyopathy. Cardiovascular dysfunction in MS is incompletely understood and likely underrecognized. REVIEW SUMMARY: The clinical presentation and pathophysiology of cardiovascular dysfunction in MS are reviewed, as are the cardiovascular toxicities of MS therapies, fingolimod and mitoxantrone. Cardiovascular dysfunction in MS can be caused by brainstem lesions affecting autonomic pathways in the medulla, overall plaque burden, and clinical severity of the disease. CONCLUSIONS: Cardiovascular abnormalities may be clinical or subclinical, and can lead to sudden death in some cases. Neurologists should be aware of the clinical presentation and pathophysiology of cardiovascular dysfunction in MS so as to ameliorate cardiovascular symptoms, prevent cardiovascular complications, and choose therapeutic agents that do not worsen underlying cardiovascular disease. PMID- 26671746 TI - Crystal Chemistry of the New Families of Interstitial Compounds R6Mg23C (R = La, Ce, Pr, Nd, Sm, or Gd) and Ce6Mg23Z (Z = C, Si, Ge, Sn, Pb, P, As, or Sb). AB - The crystal chemical features of the new series of compounds R6Mg23C with R = La Sm or Gd and Ce6Mg23Z with Z = C, Si, Ge, Sn, Pb, P, As, or Sb have been studied by means of single-crystal and powder X-ray diffraction techniques. All phases crystallize with the cubic Zr6Zn23Si prototype (cF120, space group Fm3m, Z = 4), a filled variant of the Th6Mn23 structure. While no Th6Mn23-type binary rare earth-magnesium compound is known to exist, the addition of a third element Z (only 3 atom %), located into the octahedral cavity of the Th6Mn23 cell (Wyckoff site 4a), stabilizes this structural arrangement and makes possible the formation of the ternary R6Mg23Z compounds. The results of both structural and topological analyses as well as of LMTO electronic structure calculations show that the interstitial element plays a crucial role in the stability of these phases, forming a strongly bonded [R6Z] octahedral moiety spaced by zeolite cage-like [Mg45] clusters. Considering these two building units, the crystal structure of these apparently complex intermetallics can be simplified to the NaCl-type topology. Moreover, a structural relationship between RMg3 and R6Mg23C compounds has been unveiled; the latter can be described as substitutional derivatives of the former. The geometrical distortions and the consequent symmetry reduction that accompany this transformation are explicitly described by means of the Barnighausen formalism within group theory. PMID- 26671745 TI - Zebrafish heart as a model for human cardiac electrophysiology. AB - The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart. PMID- 26671747 TI - Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial. AB - BACKGROUND: Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment. METHODS: First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non eradicated patients (n=17) at 1 year among the H. pylori-positive patients. RESULTS: Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points). CONCLUSIONS: H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM. PMID- 26671748 TI - Has the survival of patients with glioblastoma changed over the years? AB - BACKGROUND: Over the last decade, the approach to the management of brain tumours and the understanding of glioblastoma tumour biology has advanced and a number of therapeutic interventions have evolved, some of which have shown statistically significant effects on overall survival (OS) and progression-free survival in glioblastoma. The aim of this study is to compare survival in glioblastoma patients over a 10-year period (1999-2000 and 2009-2010). METHODS: A retrospective cohort study was performed. Identification of all histologically confirmed glioblastoma in a single centre in years 1999, 2000, 2009 and 2010, and production of survival analysis comparing 1999-2000 and 2009-2010 were achieved. RESULTS: A total of 317 patients were included in the analysis (133 in year 1999 2000, and 184 in year 2009-2010). Cox regression analysis showed that the survival was significantly longer in patients in years 2009-2010 than those in 1999-2000 at P<0.001 with HR=0.56, confidence interval (CI) (0.45-0.71). The 1- and 3-year survival rates were 20.7% and 4.4%, respectively, for patients in 1999 2000, improving to 40.0% and 10.3%, respectively, for patients in 2009-2010. The comparisons between the two groups in survival at 1, 2 and 3 years are all statistically significant at P<0.001, respectively. The median OS was 0.36 and 0.74 in 1999-2000 and 2009-2010 groups, respectively. CONCLUSIONS: Over this period, OS from glioblastoma has increased significantly in our unit. We believe this is due to the institution of evidence-based surgical and oncological strategies practised in a multidisciplinary setting. PMID- 26671749 TI - A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. AB - BACKGROUND: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups. METHODS: We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients. RESULTS: The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples. CONCLUSIONS: The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs. PMID- 26671750 TI - Melanoma-expressed CD70 is involved in invasion and metastasis. AB - BACKGROUND: CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation. METHODS: We evaluated the expression of CD70 in biopsies and melanoma cell lines. Using melanoma cell lines positive or not for CD70, we analysed CD70 function on melanoma progression. RESULTS: We report CD70 expression in human melanoma cell lines and tumour cells from melanoma biopsies. This expression was observed in 95% of primary melanomas but only 37% of metastases. Both monomeric and trimeric forms of CD70 were detected in tumour cell membrane fractions, whereas cytoplasmic fractions contained almost exclusively monomeric CD70. In vitro and in vivo experiments demonstrated that CD70 expression inhibited melanoma cell migration, invasion and pulmonary metastasis implantation independently of the tumour immune microenvironment. Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance. CONCLUSIONS: Our results describe a new non-immunological function of melanoma-expressed CD70, which involves melanoma invasiveness through MAPK pathway, RhoE and cytoskeletal modulation. PMID- 26671751 TI - An unusual ocular complication following dental anaesthesia: case report. AB - Used routinely by dental practitioners, local anaesthetics are generally a safe and effective means of achieving pain control during invasive dental procedures. Delivery, however, is technique sensitive and the potential for patient complication exists. Although reasonably rare, ocular complications have occurred, often leaving the patient and the clinician in distress. Such reported events have almost always involved tissue responses ipsilateral to the injection site. The current case report presents an unusual event involving involuntary fasciculation or hemifacial spasm and eventual eyelid closure on the contralateral side following a routine inferior alveolar nerve block. Aspects including the patient's history, the observed response, a pathophysiological hypothesis and patient management are discussed. PMID- 26671752 TI - The Association Between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study. AB - Several studies have shown an association between overt hypothyroidism and diastolic hypertension. Association between subclinical hypothyroidism and hypertension is a matter of debate. The aim of this study was to examine the association of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure with serum thyroid hormones levels in euthyroid subjects.Data from 4 756 individuals of the Tehran Thyroid study (TTS) without any previously known thyroid disease were analyzed. We divided participants based on TSH tertiles. Serum TSH and free T4 (FT4) concentration, systolic blood pressure (SBP), diastolic blood pressure (BPD) body mass index (BMI) were measured in all subjects.Among 5 786 individuals participated, 4 985 were euthyroid. After implementing exclusion criteria, 4 756 individuals remained of whom 2 122 (44.6%) were male and 2 634 (55.4%) were female. Multiple linear regression analysis revealed no association between TSH levels within reference ranges and blood pressure profile. No significant relationship was observed between TSH levels and systolic or diastolic blood pressure or the mean arterial pressure or pulse pressure in each tertile of TSH. There was a negative association between pulse pressure and TSH in the second tertile (r=- 0.066, p=0.009). Regression analysis showed that FT4 was significantly associated with systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure.No association was found between serum TSH and blood pressure profile in euthyroid subjects. Serum FT4 levels showed a positive association with blood pressure profiles. PMID- 26671755 TI - Including the excluded: Males and gender minorities in eating disorder prevention. PMID- 26671753 TI - Construction of a Rapid Feather-Degrading Bacterium by Overexpression of a Highly Efficient Alkaline Keratinase in Its Parent Strain Bacillus amyloliquefaciens K11. AB - Keratinase is essential to degrade the main feather component, keratin, and is of importance for wide industrial applications. In this study, Bacillus amyloliquefaciens strain K11 was found to have significant feather-degrading capacity (completely degraded whole feathers within 24 h). The keratinase encoding gene, kerK, was expressed in Bacillus subtilis SCK6. The purified recombinant KerK showed optimal activity at 50 degrees C and pH 11.0 and degraded whole feathers within 0.5 h in the presence of DTT. The recombinant plasmids harboring kerK were extracted from B. subtilis SCK6 and transformed into B. amyloliquefaciens K11. As a result, the recombinant B. amyloliquefaciens K11 exhibited enhanced feather-degrading capacity with shortened reaction time within 12 h and increased keratinolytic activity (1500 U/mL) by 6-fold. This efficient and rapid feather-degrading character makes the recombinant strain of B. amyloliquefaciens K11 have potential for applications in feather meal preparation and waste feather disposal. PMID- 26671754 TI - Refining the continuum of CFTR-associated disorders in the era of newborn screening. AB - Clinical heterogeneity in cystic fibrosis (CF) often causes diagnostic uncertainty in infants without symptoms and in older patients with milder phenotypes. We performed a cross-sectional evaluation of a comprehensive set of clinical and laboratory descriptors in a physician-defined cohort (N = 376; Children's Hospital of Wisconsin and the American Family Children's Hospital CF centers in Milwaukee and Madison, WI, USA) to determine the robustness of categorizing CF (N = 300), cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (N = 19), and CFTR-related (CRMS) metabolic syndrome (N = 57) according to current consensus guidelines. Outcome measures included patient demographics, clinical measures, sweat chloride levels, CFTR genotype, age at diagnosis, airway microbiology, pancreatic function, infection, and nutritional status. The CF cohort had a significantly higher median sweat chloride level (105 mmol/l) than CFTR-related disorder patients (43 mmol/l) and CFTR-related metabolic syndrome patients (35 mmol/l; p <= 0.001). Patient groups significantly differed in pancreatic sufficiency, immunoreactive trypsinogen levels, sweat chloride values, genotype, and positive Pseudomonas aeruginosa cultures (p <= 0.001). An automated classification algorithm using recursive partitioning demonstrated concordance between physician diagnoses and consensus guidelines. Our analysis suggests that integrating clinical information with sweat chloride levels, CFTR genotype, and pancreatic sufficiency provides a context for continued longitudinal monitoring of patients for personalized and effective treatment. PMID- 26671756 TI - Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects. Foreword. PMID- 26671758 TI - Accurate identification of members of the Burkholderia cepacia complex in cystic fibrosis sputum. AB - The Burkholderia cepacia complex (BCC) is a group of closely related species which includes opportunistic pathogens causing chronic respiratory infections in immunocompromised patients, or individuals affected by cystic fibrosis (CF). Other Burkholderia species causing infection in the CF population are Burkholderia gladioli and Burkholderia pseudomallei. Traditional phenotypic analyses have been demonstrated to be inadequate for reliable identifications of isolates of BCC and B. gladioli. A pan-genomic analysis approach was used to design species-specific probes for Burkholderia cenocepacia, B. cepacia, Burkholderia multivorans, Burkholderia vietnamiensis, Burkholderia ambifaria, Burkholderia dolosa, Burkholderia pyrrocinia and B. gladioli. Multiplex real-time PCR assay was developed and tested using sputum specimens collected from CF patients spiked with Burkholderia species. The assay exhibited 100% sensitivity for all eight target species and detected 10(2) to 10(3) CFU ml(-1) when applied to spiked sputum. Our PCR assay resulted highly specific for each of the Burkholderia species tested, allowing discrimination among Burkholderia and non Burkholderia pathogens. Analysis carried out on 200 sputa positive for the presence of Burkholderia revealed that PCR assay and recA sequencing were fully comparable for identification of Burkholderia at the level of species. SIGNIFICANCE AND IMPACT OF THE STUDY: Burkholderia cepacia complex (BCC) has a complex taxonomic organization and its identification is a challenge for microbiology laboratories. Nonidentification or misidentification of BCC isolates represent a problem in epidemiology and treatment of cystic fibrosis patients. The high specificity and sensitivity of the multiplex Real-time PCR assay developed in this study indicates its potential to be a rapid and reliable method for the detection of Burkholderia at the level of species from sputum samples of cystic fibrosis patients. PMID- 26671759 TI - GFP-complementation assay to detect functional CPP and protein delivery into living cells. AB - Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell's membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID- 26671760 TI - Plant growth-promoting Burkholderia species isolated from annual ryegrass in Portuguese soils. AB - AIMS: To search for culturable Burkholderia species associated with annual ryegrass in soils from natural pastures in Portugal, with plant growth-promoting effects. METHODS AND RESULTS: Annual ryegrass seedlings were used to trap Burkholderia from two different soils in laboratory conditions. A combined approach using genomic fingerprinting and sequencing of 16S rRNA and recA genes resulted in the identification of Burkholderia strains belonging to the species Burkholderia graminis, Burkholderia fungorum and the Burkholderia cepacia complex. Most strains were able to solubilize mineral phosphate and to synthesize indole acetic acid; some of them could produce siderophores and antagonize the phytopathogenic oomycete, Phytophthora cinnamomi. A strain (G2Bd5) of B. graminis was selected for gnotobiotic plant inoculation experiments. The main effects were the stimulation of root growth and enhancement of leaf lipid synthesis and turnover. Fluorescence in situ hybridization and confocal laser microscopy evidenced that strain G2Bd5 is a rhizospheric and endophytic colonizer of annual ryegrass. CONCLUSIONS: This work revealed that annual ryegrass can naturally associate with members of the genus Burkholderia. A novel plant growth promoting strain of B. graminis was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel strain belongs to the plant-associated Burkholderia cluster and is a promising candidate for exploitation as plant inoculant in field conditions. PMID- 26671761 TI - Comparison of cardiac output measurements using transpulmonary thermodilution and conventional thermodilution techniques in anaesthetized dogs with fluid overload. AB - OBJECTIVE: To evaluate the agreement between cardiac output (CO) values obtained using a transpulmonary thermodilution technique (TPTDCO) and conventional thermodilution technique (TDCO) in anaesthetized dogs with fluid overload. STUDY DESIGN: Prospective experimental study. ANIMALS: Six healthy Beagle dogs aged 7-8 years. METHODS: Dogs were anaesthetized with sevoflurane in oxygen, and catheters were inserted for TPTDCO and TDCO measurement. After instrumentation, baseline CO was measured using each technique at a central venous pressure (CVP) of 3-7 mmHg. Dogs were subsequently administered lactated Ringer's solution and 6% hydroxyethyl starch to induce fluid overload. CO measurements were obtained using each technique at CVP values of 8-12 mmHg, 13-17 mmHg, 18-22 mmHg and 23-27 mmHg. Agreements between CO measurements obtained with the respective techniques were analysed using Dunnett's test, Pearson's correlation coefficient and Bland-Altman analysis. RESULTS: Thirty pairs of CO values were obtained, ranging from 1.45 L minute(-1) to 4.69 L minute(-1) for TPTDCO and from 1.30 L minute(-1) to 4.61 L minute(-1) for TDCO. TPTDCO and TDCO values correlated strongly (r(2) = 0.915, p < 0.001). The bias and mean relative bias between TPTDCO and TDCO were 0.26 +/- 0.30 L minute(-1) (limits of agreement - 0.29 to 0.81 L minute(-1) ) and 9.7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: TPTDCO and TDCO measurements obtained in anaesthetized dogs during fluid overload exhibited good agreement. Accordingly, transpulmonary thermodilution provides an accurate measurement of CO in dogs with fluid overload. PMID- 26671763 TI - Comparing generativist and constructivist accounts of the use of the past tense form in early child Japanese. AB - The present study investigated children's early use of verb inflection in Japanese by comparing a generativist account, which predicts that the past tense will have a special default-like status for the child during the early stages, with a constructivist input-driven account, which assumes that children's acquisition and use of inflectional forms reflects verb-specific distributional patterns in their input. Analysis of naturalistic data from four Japanese children aged 1;5 to 2;10 showed that there was substantial by-verb variation in the use of inflectional forms from the earliest stages of verb use, and no general preference for past tense forms. Correlational and partial correlational analyses showed that it was possible to predict the proportional frequency with which the child produced verbs in past tense versus other inflectional forms on the basis of differences in the proportional frequency with which the verb occurred in past tense form in the child's input, even after controlling for differences in the rate at which verbs occurred in past tense form in input averaged across the caregivers of the other children in the sample. When taken together, these results count against the idea that the past tense has a special default-like status in early child Japanese, and in favour of a constructivist input-driven account of children's early use of verb inflection. PMID- 26671757 TI - Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects. AB - Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right-precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The electrocardiographic manifestations of BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator is the most widely accepted approach to therapy. Pharmacologic therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential (AP) and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an implantable cardioverter defibrillator is not possible. Isoproterenol, cilostazol, and milrinone boost calcium channel current and drugs like quinidine, bepridil, and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the AP notch and thus to suppress the substrate and trigger for ventricular tachycardia or fibrillation. Radiofrequency ablation of the right ventricular outflow tract epicardium of patients with BrS has recently been shown to reduce arrhythmia vulnerability and the electrocardiographic manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular, and cellular aspects of BrS as well as the approach to therapy. PMID- 26671762 TI - Proteome Analysis of Ground State Pluripotency. AB - The differentiation potential of pluripotent embryonic stem cells (ESCs) can be manipulated via serum and medium conditions for direct cellular development or to maintain a naive ground state. The self-renewal state of ESCs can thus be induced by adding inhibitors of mitogen activated protein kinase (MAPK) and glycogen synthase kinase-3 (Gsk3), known as 2 inhibitors (2i) treatment. We have used a shotgun proteomics approach to investigate differences in protein expressions between 2i- and serum-grown mESCs. The results indicated that 164 proteins were significantly upregulated and 107 proteins downregulated in 2i-grown cells compared to serum. Protein pathways in 2i-grown cells with the highest enrichment were associated with glycolysis and gluconeogenesis. Protein pathways related to organ development were downregulated in 2i-grown cells. In serum-grown ESCs, protein pathways involved in integrin and focal adhesion, and signaling proteins involved in the actin cytoskeleton regulation were enriched. We observed a number of nuclear proteins which were mostly involved in self-renewal maintenance and were expressed at higher levels in 2i compared to serum - Dnmt1, Map2k1, Parp1, Xpo4, Eif3g, Smarca4/Brg1 and Smarcc1/Baf155. Collectively, the results provided an insight into the key protein pathways used by ESCs in the ground state or metastable conditions through 2i or serum culture medium, respectively. PMID- 26671764 TI - Multiple specificities of immunoglobulin M in equine fetuses infected with Leptospira interrogans indicate a competent immune response. AB - REASONS FOR PERFORMING STUDY: Foals of mares infected with Leptospira interrogans serovar Pomona type kennewicki (Lk) may be aborted/stillborn or delivered as healthy foals. Is fetal survival explained in part by the immune response of the fetus to Leptospira antigens? OBJECTIVES: To describe an outbreak of Leptospira abortion in which infected mares delivered dead/sick or normal foals and determine specificities of antibody in a collection of 54 fetuses from similar outbreaks. STUDY DESIGN: Outbreak investigation in combination with a case control study of a larger set of samples from aborted fetuses. METHODS: Serology and polymerase chain reaction (PCR) on urine and amniotic fluids were used to diagnose infection during an outbreak of Leptospira abortion. Specificities of immunoglobulin (Ig)M, IgGa and IgGb for recombinant proteins of Lk in archived fluids of fetuses from similar outbreaks were compared by ELISA with those of fluids of fetuses not infected with Leptospira spp. RESULTS: Five fetuses of 11 infected mares in an outbreak survived in utero in the presence of persistent placental infection and were healthy at foaling. Fetuses of 6 mares in the outbreak were aborted or died soon after birth. Significantly greater (P<0.05) IgM reactivity with all recombinant proteins and with Lk sonicate was observed in 54 archived fluids from Leptospira infected fetuses than in fluids of 30 of non Leptospira infected fetuses. Low levels of IgGa and IgGb specific for LipL32 and Lk sonicate and traces of LigA and Hsp15 specific IgGa were detected in a minority of archived fluids from Leptospira infected fetuses. CONCLUSION: Although mainly mediated by IgM, a high level of immune competence in aborted fetuses was evidenced by the multiplicity of Leptospira proteins targeted. This is likely to contribute to survival of foals in mares with evidence of placental infection at foaling as detailed in a typical outbreak. PMID- 26671765 TI - The incorporation of water-soluble gel matrix into bile acid-based microcapsules for the delivery of viable beta-cells of the pancreas, in diabetes treatment: biocompatibility and functionality studies. AB - In recent studies, we microencapsulated pancreatic beta-cells using sodium alginate (SA) and poly-L-ornithine (PLO) and the bile acid, ursodeoxycholic acid (UDCA), and tested the morphology and cell viability post-microencapsulation. Cell viability was low probably due to limited strength of the microcapsules. This study aimed to assess a beta-cell delivery system which consists of UDCA based microcapsules incorporated with water-soluble gel matrix. The polyelectrolytes, water-soluble gel (WSG), polystyrenic sulphate (PSS), PLO and polyallylamine (PAA) at ratios 4:1:1:2.5 with or without 4% UDCA, were incorporated into our microcapsules, and cell viability, metabolic profile, cell functionality, insulin production, levels of inflammation, microcapsule morphology, cellular distribution, UDCA partitioning, biocompatibility, thermal and chemical stabilities and the microencapsulation efficiency were examined. The incorporation of UDCA with PSS, PAA and WSG enhanced cell viability per microcapsule (p < 0.05), cellular metabolic profile (p < 0.01) and insulin production (p < 0.01); reduced the inflammatory release TNF-alpha (p < 0.01), INF gamma (p < 0.01) and interleukin-6 (IL-6) (p < 0.01); and ceased the production of IL-1beta. UDCA, PSS, PAA and WSG addition did not change the microencapsulation efficiency and resulted in biocompatible microcapsules. Our designed microcapsules showed good morphology and desirable insulin production, cell functionality and reduced inflammatory profile suggesting potential applications in diabetes. PMID- 26671767 TI - How Plasticity and Evolution Work in the Real World. PMID- 26671766 TI - Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells. AB - Lipid composition of membranes is fundamental to modulate signaling pathways relying on lipid metabolites and/or membrane proteins, thus resulting in the regulation of important cell processes such as apoptosis. In this case, membrane remodeling is an early event important for the activation of signaling leading to cell death and removal of apoptotic cells. In the present study, we analyzed phospholipid, cholesterol and fatty acid content during apoptosis induced by manganese in PC12 cells. Lipid analysis of whole cells and detergent-resistant membranes was carried out by HPLC/GC. Results showed that apoptosis is associated with changes in lipid composition detectable in whole cell extracts, namely cholesterol, phosphatidylserine and phosphatidylethanolamine decreases. Noteworthy, phosphatidylserine level reduction was detectable before to the detection of apoptosis, in correlation with our previous study carried out by radioactive labelling. By contrast, phosphatidylserine and phosphatidylethanolamine changes were not detected in detergent resistant membranes, which instead showed an altered composition in phosphatidylinositol, phosphatidylcholine and sphingomyelin in apoptotic cells. PMID- 26671773 TI - Looking for the remedies. PMID- 26671774 TI - Auditory Streaming as an Online Classification Process with Evidence Accumulation. AB - When human subjects hear a sequence of two alternating pure tones, they often perceive it in one of two ways: as one integrated sequence (a single "stream" consisting of the two tones), or as two segregated sequences, one sequence of low tones perceived separately from another sequence of high tones (two "streams"). Perception of this stimulus is thus bistable. Moreover, subjects report on-going switching between the two percepts: unless the frequency separation is large, initial perception tends to be of integration, followed by toggling between integration and segregation phases. The process of stream formation is loosely named "auditory streaming". Auditory streaming is believed to be a manifestation of human ability to analyze an auditory scene, i.e. to attribute portions of the incoming sound sequence to distinct sound generating entities. Previous studies suggested that the durations of the successive integration and segregation phases are statistically independent. This independence plays an important role in current models of bistability. Contrary to this, we show here, by analyzing a large set of data, that subsequent phase durations are positively correlated. To account together for bistability and positive correlation between subsequent durations, we suggest that streaming is a consequence of an evidence accumulation process. Evidence for segregation is accumulated during the integration phase and vice versa; a switch to the opposite percept occurs stochastically based on this evidence. During a long phase, a large amount of evidence for the opposite percept is accumulated, resulting in a long subsequent phase. In contrast, a short phase is followed by another short phase. We implement these concepts using a probabilistic model that shows both bistability and correlations similar to those observed experimentally. PMID- 26671775 TI - Predictive factors associated with failure of nonoperative treatment of superior labrum anterior-posterior tears. AB - BACKGROUND: Uncertainty remains in the natural course of superior labrum anterior posterior (SLAP) tears treated conservatively with rehabilitation and activity modification. Our purpose was to evaluate clinical outcomes after nonoperative treatment of type II SLAP tear in young active patients and to identify factors related to negative outcomes. METHODS: We retrospectively reviewed 63 patients who initially underwent nonoperative treatment for isolated type II SLAP tear. Assessments were made at baseline and at 6 months, and telephone survey was used to evaluate the final outcome. All included patients underwent a consistent nonoperative treatment protocol, and patient-specific data on the outcome were assessed. Failure was defined as abandonment of nonoperative management for surgery at any time points, <20-point improvement in American Shoulder and Elbow Surgeons score at final follow-up, or inability to return to activities. RESULTS: At the average follow-up of 21 months, pain relief and function improved significantly (American Shoulder and Elbow Surgeons score, 54.2-86.4; Visual Analog Scale score, 4.6-1.7; P < .05) in 45 patients (71.4%) with successful nonoperative treatment. Eighteen patients (28.5%) were either dissatisfied with treatment or had arthroscopic surgery and were considered a failure group. Multivariate analysis showed that failure of nonoperative treatment is strongly linked with history of trauma, positive compression-rotation test result, and participation in overhead activities (P < .05). CONCLUSIONS: An initial trial of nonoperative management may be considered in young active patients with isolated SLAP tear. Patients with history of trauma, mechanical symptoms, and demand for overhead activities are less likely to succeed. PMID- 26671776 TI - Anteroinferior versus superior plating of clavicular fractures. AB - BACKGROUND: Open reduction and plate fixation has gained recognition as an effective treatment for certain types of clavicular fractures. However, 88% of cases report some implant-related problems. To determine the optimal plate position, the aim of the present study was to compare implant-related irritation and proportion of plate removal in patients with clavicular fractures undergoing plate fixation by an anteroinferior or superior approach. METHODS: Retrospectively collected data of 39 patients who underwent anteroinferior plating for displaced midshaft clavicular fractures were compared with prospectively collected data of 60 patients who were treated with superior plate fixation as part of a multicenter randomized controlled trial. Electronic medical records were reviewed for reports of complications, in particular, implant related irritation and implant removal during follow-up. In addition, all patients were contacted in June 2014 to obtain additional information. The primary outcome parameter was implant-related irritation. RESULTS: Univariate and multivariate regression analysis showed plate position was not significantly associated with implant-related irritation. Higher rates of asymptomatic patients with the plate still in place were observed in the anteroinferior group (46% vs 22%, P = .01). Almost an equal percentage of implant removals was seen in both groups because of implant irritation (36% vs 37%, P = .938). CONCLUSIONS: The present study found the surgical approach of clavicular plating was not associated with implant-related irritation. Future studies are needed to determine whether there is an optimal approach for clavicle plating. PMID- 26671777 TI - Correction: The N-glycan Glycoprotein Deglycosylation Complex (Gpd) from Capnocytophaga canimorsus Deglycosylates Human IgG. PMID- 26671778 TI - Unveiling Bacterial Interactions through Multidimensional Scaling and Dynamics Modeling. AB - We propose a new strategy to identify and visualize bacterial consortia by conducting replicated culturing of environmental samples coupled with high throughput sequencing and multidimensional scaling analysis, followed by identification of bacteria-bacteria correlations and interactions. We conducted a proof of concept assay with pine-tree resin-based media in ten replicates, which allowed detecting and visualizing dynamical bacterial associations in the form of statistically significant and yet biologically relevant bacterial consortia. PMID- 26671780 TI - Defect-free thin InAs nanowires grown using molecular beam epitaxy. AB - In this study, we designed a simple method to achieve the growth of defect-free thin InAs nanowires with a lateral dimension well below their Bohr radius on different substrate orientations. By depositing and annealing a thin layer of Au thin film on a (100) substrate surface, we have achieved the growth of defect free uniform-sized thin InAs nanowires. This study provides a strategy to achieve the growth of pure defect-free thin nanowires. PMID- 26671779 TI - Stochasticity and homeostasis in the E. coli replication and division cycle. AB - How cells correct for stochasticity to coordinate the chromosome replication and cellular division cycle is poorly understood. We used time-lapse microscopy and fluorescently labelled SeqA to determine the timing of birth, initiation, termination, and division, as well as cell size throughout the cell cycle. We found that the time between birth and initiation (B-period) compensates for stochastic variability in birth size and growth rate. The time between termination and division (D-period) also compensates for size and growth variability, invalidating the notion that replication initiation is the principal trigger for cell division. In contrast, the time between initiation and termination (C-period) did not display such compensations. Interestingly, the C period did show small but systematic decreases for cells that spontaneously grew faster, which suggests a coupling between metabolic fluctuations and replication. An auto-regressive theoretical framework was employed to compare different possible models of sub-period control. PMID- 26671781 TI - Likelihood Ratio Test for Excess Homozygosity at Marker Loci on X Chromosome. AB - The assumption of Hardy-Weinberg equilibrium (HWE) is generally required for association analysis using case-control design on autosomes; otherwise, the size may be inflated. There has been an increasing interest of exploring the association between diseases and markers on X chromosome and the effect of the departure from HWE on association analysis on X chromosome. Note that there are two hypotheses of interest regarding the X chromosome: (i) the frequencies of the same allele at a locus in males and females are equal and (ii) the inbreeding coefficient in females is zero (without excess homozygosity). Thus, excess homozygosity and significantly different minor allele frequencies between males and females are used to filter X-linked variants. There are two existing methods to test for (i) and (ii), respectively. However, their size and powers have not been studied yet. Further, there is no existing method to simultaneously detect both hypotheses till now. Therefore, in this article, we propose a novel likelihood ratio test for both (i) and (ii) on X chromosome. To further investigate the underlying reason why the null hypothesis is statistically rejected, we also develop two likelihood ratio tests for detecting (i) and (ii), respectively. Moreover, we explore the effect of population stratification on the proposed tests. From our simulation study, the size of the test for (i) is close to the nominal significance level. However, the size of the excess homozygosity test and the test for both (i) and (ii) is conservative. So, we propose parametric bootstrap techniques to evaluate their validity and performance. Simulation results show that the proposed methods with bootstrap techniques control the size well under the respective null hypothesis. Power comparison demonstrates that the methods with bootstrap techniques are more powerful than those without bootstrap procedure and the existing methods. The application of the proposed methods to a rheumatoid arthritis dataset indicates their utility. PMID- 26671782 TI - Factors Associated with Tremor Changes during Sedation with Dexmedetomidine in Parkinson's Disease Surgery. AB - INTRODUCTION: Dexmedetomidine is an alpha2-agonist recently proposed as a potentially ideal drug for sedation during the surgical treatment of Parkinson's disease (PD). This report documents the incidence of changes in motor symptoms (especially tremor) in PD patients sedated with dexmedetomidine for deep brain stimulation or ablation procedures. METHODS: We reviewed a retrospective cohort of 22 patients who underwent surgery for PD with dexmedetomidine sedation at a single institution from 2010 to 2014. A logistic regression analysis was performed to analyze possible confounding factors. RESULTS: 14 cases of tremor reduction or suppression were recorded (cumulative incidence: 63.6%; 95% CI: 40.7 82.8). No association could be identified between loading dose, beta-blocker use and preoperative total Unified Parkinson's Disease Rating Scale III, with tremor changes. The maintenance dose of dexmedetomidine was higher in patients who did not experience changes [median and range for patients with and without tremor alteration 0.75 (0.2-1.0) and 1.0 ug * kg(-1) * h(-1) (0.7-1.4), respectively; p = 0.021]. CONCLUSION: Dexmedetomidine provides adequate sedation during surgery for PD, but it might affect motor signs making intraoperative testing difficult or even impossible. Dosage appears not to be the determining factor in motor changes, whose cause remains unclear. PMID- 26671783 TI - A Soft 3D Acoustic Metafluid with Dual-Band Negative Refractive Index. AB - Spherical silica xerogels are efficient acoustic Mie resonators. When these sub wavelength inclusions are dispersed in a matrix, the final metafluid may display a negative acoustic refractive index upon a set of precise constraints concerning material properties, concentration, size, and dispersity of the inclusions. Because xerogels may sustain both pressure and shear waves, several bands with negative index can be tailored. PMID- 26671784 TI - Ex vivo estimation of cementless acetabular cup stability using an impact hammer. AB - Obtaining primary stability of acetabular cup (AC) implants is one of the main objectives of press-fit procedures used for cementless hip arthroplasty. The aim of this study is to investigate whether the AC implant primary stability can be evaluated using the signals obtained with an impact hammer. A hammer equipped with a force sensor was used to impact the AC implant in 20 bovine bone samples. For each sample, different stability conditions were obtained by changing the cavity diameter. For each configuration, the inserted AC implant was impacted four times with a maximum force comprised between 2500 and 4500 N. An indicator I was determined based on the partial impulse estimation and the pull-out force was measured. The implant stability and the value of the indicator I reached a maximum value for an interference fit equal to 1 mm for 18 out of 20 samples. When pooling all samples and all configurations, the implant stability and I were significantly correlated (R(2) = 0.83). The AC implant primary stability can be assessed through the analysis of the impact force signals obtained using an impact hammer. Based on these ex vivo results, a medical device could be developed to provide a decision support system to the orthopedic surgeons. PMID- 26671785 TI - Mesh management methods in finite element simulations of orthodontic tooth movement. AB - In finite element simulations of orthodontic tooth movement, one of the challenges is to represent long term tooth movement. Large deformation of the periodontal ligament and large tooth displacement due to bone remodelling lead to large distortions of the finite element mesh when a Lagrangian formalism is used. We propose in this work to use an Arbitrary Lagrangian Eulerian (ALE) formalism to delay remeshing operations. A large tooth displacement is obtained including effect of remodelling without the need of remeshing steps but keeping a good quality mesh. Very large deformations in soft tissues such as the periodontal ligament is obtained using a combination of the ALE formalism used continuously and a remeshing algorithm used when needed. This work demonstrates that the ALE formalism is a very efficient way to delay remeshing operations. PMID- 26671786 TI - Immunohistochemical localization of keratin 5 in the submandibular gland in adult and postnatal developing mice. AB - Keratin 5 (K5) is a marker of basal progenitor cells in the epithelia of a number of organs. During prenatal development of the submandibular gland (SMG) in mice, K5(+) progenitor cells in the developing epithelia play important roles in its organogenesis. Although K5(+) cells are also present in the adult mouse SMG and may function in tissue regeneration, their histological localization has not yet investigated in detail. In the present study, we examined the immunohistochemical localization of K5 in the SMG in adult and postnatal developing mice. At birth, K5 immunoreactivity was detected in the entire duct system, in which it was localized in the basal cells of a double-layered epithelium, but was not detected in the terminal tubule or myoepithelial cells. At postnatal weeks 1-3, with the development of intercalated ducts (ID), striated ducts (SD), and excretory ducts (ED), K5-immunoreactive basal cells were gradually restricted to the ED and the proximal double-layered portions of the ID connecting to the SD. At the same time, K5 immunoreactivity appeared in myoepithelial cells, in which its positive ratio gradually increased. In adults, K5 immunoreactivity was localized to most myoepithelial cells, most basal cells in the ED, and a small number of ID cells at the boundary between the ID and SD in the female SMG or between the ID and granular convoluted tubules in the male SMG. These results suggest that K5 is a marker of differentiated myoepithelial cells and duct progenitor cells in the mouse SMG. PMID- 26671787 TI - Phospholipase C-eta2 interacts with nuclear and cytoplasmic LIMK-1 during retinoic acid-stimulated neurite growth. AB - Neurite growth is central to the formation and differentiation of functional neurons, and recently, an essential role for phospholipase C-eta2 (PLCeta2) in neuritogenesis was revealed. Here we investigate the function of PLCeta2 in neuritogenesis using Neuro2A cells, which upon stimulation with retinoic acid differentiate and form neurites. We first investigated the role of the PLCeta2 calcium-binding EF-hand domain, a domain that is known to be required for PLCeta2 activation. To do this, we quantified neurite outgrowth in Neuro2A cells, stably overexpressing wild-type PLCeta2 and D256A (EF-hand) and H460Q (active site) PLCeta2 mutants. Retinoic acid-induced neuritogenesis was highly dependent on PLCeta2 activity, with the H460Q mutant exhibiting a strong dominant-negative effect. Expression of the D256A mutant had little effect on neurite growth relative to the control, suggesting that calcium-directed activation of PLCeta2 is not essential to this process. We next investigated which cellular compartments contain endogenous PLCeta2 by comparing immunoelectron microscopy signals over control and knockdown cell lines. When signals were analyzed to reveal specific labeling for PLCeta2, it was found to be localized predominantly over the nucleus and cytosol. Furthermore in these compartments (and also in growing neurites), a proximity ligand assay revealed that PLCeta2 specifically interacts with LIMK-1 in Neuro2A cells. Taken together, these data emphasize the importance of the PLCeta2 EF-hand domain and articulation of PLCeta2 with LIMK-1 in regulating neuritogenesis. PMID- 26671789 TI - Long-term stability of carrier-added (68)Ge standardized solutions. AB - Tests for chemical stability were carried out on carrier-added (68)Ge solutions prepared and calibrated in 2007 and 2011 to evaluate the suitability of the specific composition as a potential Standard Reference Material. Massic count rates of the stored solutions were measured using a NaI(Tl) well counter before and after gravimetric transfers. The present activity concentration of the 2007 solution was also measured using live-timed anticoincidence counting (LTAC) and compared to the 2007 calibrated value. The well counter data indicated no change in massic count rate to within uncertainties for either solution. The LTAC measurements gave a difference of -0.49% in the activity concentration 2007 solution over 7 years. However, the uncertainty in the decay correction over that time, due to the uncertainty in the (68)Ge half-life, accounted for the majority (0.67% out of 0.83%) of the standard uncertainty on the activity concentration. The results indicate that these carrier-added solutions are stable with regard to potential activity losses over several half-lives of (68)Ge. PMID- 26671790 TI - Measurement function for the activities of multi-gamma-ray emitters in gamma-ray spectrometric measurements. AB - In gamma-ray spectrometric measurements the background is usually taken into account by conducting measurements on a blank sample. However, this method is not appropriate if many different kinds of samples are measured and several types of detectors are used. In such cases it is easier to measure accurately the activities of the blank materials separately and then to subtract the activities of the blank sample from the total sample activities. In order to do this, the measurement function for the activity calculation must be modified. PMID- 26671788 TI - Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models. AB - Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes. PMID- 26671791 TI - Analysis of size-fractionated soil samples by gamma spectrometry. AB - The purpose of this work was to investigate the effect of particle size on radionuclides in soil, particularly in relation to depth. A set of soil samples at the 0-10cm and 10-20cm depth layers were collected, separated into size fractions using a sieving machine and analyzed by gamma spectrometry to determine (238)U, (226)Ra, (210)Pb, and (137)Cs. Significant variations between different size fractions and depth layers were observed. A 0-20cm depth profile was also investigated. PMID- 26671792 TI - Evaluation of procedures for (226)Ra determination in samples with high barium concentration by alpha-particle spectrometry. AB - The gamma emitter (133)Ba is the most often used tracer in determination of (226)Ra by alpha-particle spectrometry. If the source for alpha-particle spectrometry is prepared by microcoprecipitation, a high Ba concentration causes a thicker source layer which results in reduced counting efficiency due to self absorption on the alpha spectrometer and consequently lower result for (226)Ra, while not effecting the measurement of (133)Ba in gamma-ray spectrometry. If the electrodeposition is used, recoveries of deposited Ra and Ba are not necessarily the same and impurities of other alpha emitters may interfere with the alpha spectrum. PMID- 26671793 TI - (177)Lu: DDEP Evaluation of the decay scheme for an emerging radiopharmaceutical. AB - A new decay scheme evaluation using the DDEP methodology for (177)Lu is presented. Recently measured half-life measurements have been incorporated, as well as newly available gamma-ray emission probabilities. For the first time, a thorough investigation has been made of the gamma-ray multipolarities. The complete data tables and detailed evaluator comments are available through the DDEP website. PMID- 26671794 TI - Determination of the characteristic limits and responses of nuclear track detectors in mixed radon and thoron atmospheres. AB - Closed nuclear track detectors are widely used for the determination of Rn-222 exposures. There are also partial open systems available, which are specially designed for the determination of the exposure to Rn-220, which is a relevant exposure in special workplaces or in specific regions of the world. This paper presents data and a detail analysis of how to determine the cross-correlation by calibration in pure Rn-222 and pure Rn-220 atm. By these means calibration coefficients for the analysis of real mixed atmospheres can be obtained. The respective decision threshold, detection limit and limits of the confidence interval were determined according to ISO 11929 (ISO 11929:2010, 2010). The exposure of detectors was performed at the radon reference chamber and the thoron progeny chamber of the Physikalisch-Technische Bundesanstalt (PTB). The analysis of track response was done at Parc RGM, while the analytical routines were developed in the Leibniz University Hanover, Institute Radiookologie und Strahlenschutz IRS at the working Group AK SIGMA (Arbeitskreis Nachweisgrenzen). PMID- 26671795 TI - Cophylogenetic Reconciliation with ILP. AB - In this paper, we present an integer linear programming (ILP) approach, called CoRe-ILP, for finding an optimal time consistent cophylogenetic host-parasite reconciliation under the cophylogenetic event model with the events cospeciation, duplication, sorting, host switch, and failure to diverge. Instead of assuming event costs, a simplified model is used, maximizing primarily for cospeciations and secondarily minimizing host switching events. Duplications, sortings, and failure to diverge events are not explicitly scored. Different from existing event based reconciliation methods, CoRe-ILP can use (approximate) phylogenetic branch lengths for filtering possible ancestral host-parasite interactions. Experimentally, it is shown that CoRe-ILP can successfully use branch length information and performs well for biological and simulated data sets. The results of CoRe-ILP are compared with the results of the reconciliation tools Jane 4, Treemap 3b, NOTUNG 2.8 Beta, and Ranger-DTL. Algorithm CoRe-ILP is implemented using IBM ILOG CPLEX Optimizer 12.6 and is freely available from http://pacosy.informatik.uni-leipzig.de/core-ilp. PMID- 26671796 TI - DPNuc: Identifying Nucleosome Positions Based on the Dirichlet Process Mixture Model. AB - Nucleosomes and the free linker DNA between them assemble the chromatin. Nucleosome positioning plays an important role in gene transcription regulation, DNA replication and repair, alternative splicing, and so on. With the rapid development of ChIP-seq, it is possible to computationally detect the positions of nucleosomes on chromosomes. However, existing methods cannot provide accurate and detailed information about the detected nucleosomes, especially for the nucleosomes with complex configurations where overlaps and noise exist. Meanwhile, they usually require some prior knowledge of nucleosomes as input, such as the size or the number of the unknown nucleosomes, which may significantly influence the detection results. In this paper, we propose a novel approach DPNuc for identifying nucleosome positions based on the Dirichlet process mixture model. In our method, Markov chain Monte Carlo (MCMC) simulations are employed to determine the mixture model with no need of prior knowledge about nucleosomes. Compared with three existing methods, our approach can provide more detailed information of the detected nucleosomes and can more reasonably reveal the real configurations of the chromosomes; especially, our approach performs better in the complex overlapping situations. By mapping the detected nucleosomes to a synthetic benchmark nucleosome map and two existing benchmark nucleosome maps, it is shown that our approach achieves a better performance in identifying nucleosome positions and gets a higher F-score. Finally, we show that our approach can more reliably detect the size distribution of nucleosomes. PMID- 26671797 TI - A Cooperative Co-Evolutionary Genetic Algorithm for Tree Scoring and Ancestral Genome Inference. AB - Recent advances of technology have made it easy to obtain and compare whole genomes. Rearrangements of genomes through operations such as reversals and transpositions are rare events that enable researchers to reconstruct deep evolutionary history among species. Some of the popular methods need to search a large tree space for the best scored tree, thus it is desirable to have a fast and accurate method that can score a given tree efficiently. During the tree scoring procedure, the genomic structures of internal tree nodes are also provided, which provide important information for inferring ancestral genomes and for modeling the evolutionary processes. However, computing tree scores and ancestral genomes are very difficult and a lot of researchers have to rely on heuristic methods which have various disadvantages. In this paper, we describe the first genetic algorithm for tree scoring and ancestor inference, which uses a fitness function considering co-evolution, adopts different initial seeding methods to initialize the first population pool, and utilizes a sorting-based approach to realize evolution. Our extensive experiments show that compared with other existing algorithms, this new method is more accurate and can infer ancestral genomes that are much closer to the true ancestors. PMID- 26671798 TI - LGH: A Fast and Accurate Algorithm for Single Individual Haplotyping Based on a Two-Locus Linkage Graph. AB - Phased haplotype information is crucial in our complete understanding of differences between individuals at the genetic level. Given a collection of DNA fragments sequenced from a homologous pair of chromosomes, the problem of single individual haplotyping (SIH) aims to reconstruct a pair of haplotypes using a computer algorithm. In this paper, we encode the information of aligned DNA fragments into a two-locus linkage graph and approach the SIH problem by vertex labeling of the graph. In order to find a vertex labeling with the minimum sum of weights of incompatible edges, we develop a fast and accurate heuristic algorithm. It starts with detecting error-tolerant components by an adapted breadth-first search. A proper labeling of vertices is then identified for each component, with which sequencing errors are further corrected and edge weights are adjusted accordingly. After contracting each error-tolerant component into a single vertex, the above procedure is iterated on the resulting condensed linkage graph until error-tolerant components are no longer detected. The algorithm finally outputs a haplotype pair based on the vertex labeling. Extensive experiments on simulated and real data show that our algorithm is more accurate and faster than five existing algorithms for single individual haplotyping. PMID- 26671799 TI - A Machine Learning Based Approach to de novo Sequencing of Glycans from Tandem Mass Spectrometry Spectrum. AB - Recently, glycomics has been actively studied and various technologies for glycomics have been rapidly developed. Currently, tandem mass spectrometry (MS/MS) is one of the key experimental tools for identification of structures of oligosaccharides. MS/MS can observe MS/MS peaks of fragmented glycan ions including cross-ring ions resulting from internal cleavages, which provide valuable information to infer glycan structures. Thus, the aim of de novo sequencing of glycans is to find the most probable assignments of observed MS/MS peaks to glycan substructures without databases. However, there are few satisfiable algorithms for glycan de novo sequencing from MS/MS spectra. We present a machine learning based approach to de novo sequencing of glycans from MS/MS spectrum. First, we build a suitable model for the fragmentation of glycans including cross-ring ions, and implement a solver that employs Lagrangian relaxation with a dynamic programming technique. Then, to optimize scores for the algorithm, we introduce a machine learning technique called structured support vector machines that enable us to learn parameters including scores for cross ring ions from training data, i.e., known glycan mass spectra. Furthermore, we implement additional constraints for core structures of well-known glycan types including N-linked glycans and O-linked glycans. This enables us to predict more accurate glycan structures if the glycan type of given spectra is known. Computational experiments show that our algorithm performs accurate de novo sequencing of glycans. The implementation of our algorithm and the datasets are available at http://glyfon.dna.bio.keio.ac.jp/. PMID- 26671800 TI - CoGI: Towards Compressing Genomes as an Image. AB - Genomic science is now facing an explosive increase of data thanks to the fast development of sequencing technology. This situation poses serious challenges to genomic data storage and transferring. It is desirable to compress data to reduce storage and transferring cost, and thus to boost data distribution and utilization efficiency. Up to now, a number of algorithms / tools have been developed for compressing genomic sequences. Unlike the existing algorithms, most of which treat genomes as one-dimensional text strings and compress them based on dictionaries or probability models, this paper proposes a novel approach called CoGI (the abbreviation of Compressing Genomes as an Image) for genome compression, which transforms the genomic sequences to a two-dimensional binary image (or bitmap), then applies a rectangular partition coding algorithm to compress the binary image. CoGI can be used as either a reference-based compressor or a reference-free compressor. For the former, we develop two entropy based algorithms to select a proper reference genome. Performance evaluation is conducted on various genomes. Experimental results show that the reference-based CoGI significantly outperforms two state-of-the-art reference-based genome compressors GReEn and RLZ-opt in both compression ratio and compression efficiency. It also achieves comparable compression ratio but two orders of magnitude higher compression efficiency in comparison with XM--one state-of-the art reference-free genome compressor. Furthermore, our approach performs much better than Gzip--a general-purpose and widely-used compressor, in both compression speed and compression ratio. So, CoGI can serve as an effective and practical genome compressor. The source code and other related documents of CoGI are available at: http://admis.fudan.edu.cn/projects/cogi.htm. PMID- 26671801 TI - BMExpert: Mining MEDLINE for Finding Experts in Biomedical Domains Based on Language Model. AB - With the rapid development of biomedical sciences, a great number of documents have been published to report new scientific findings and advance the process of knowledge discovery. By the end of 2013, the largest biomedical literature database, MEDLINE, has indexed over 23 million abstracts. It is thus not easy for scientific professionals to find experts on a certain topic in the biomedical domain. In contrast to the existing services that use some ad hoc approaches, we developed a novel solution to biomedical expert finding, BMExpert, based on the language model. For finding biomedical experts, who are the most relevant to a specific topic query, BMExpert mines MEDLINE documents by considering three important factors: relevance of documents to the query topic, importance of documents, and associations between documents and experts. The performance of BMExpert was evaluated on a benchmark dataset, which was built by collecting the program committee members of ISMB in the past three years (2012-2014) on 14 different topics. Experimental results show that BMExpert outperformed three existing biomedical expert finding services: JANE, GoPubMed, and eTBLAST, with respect to both MAP (mean average precision) and P@50 (Precision). BMExpert is freely accessed at http://datamining-iip.fudan.edu.cn/service/BMExpert/. PMID- 26671802 TI - A Resampling Based Clustering Algorithm for Replicated Gene Expression Data. AB - In gene expression data analysis, clustering is a fruitful exploratory technique to reveal the underlying molecular mechanism by identifying groups of co expressed genes. To reduce the noise, usually multiple experimental replicates are performed. An integrative analysis of the full replicate data, instead of reducing the data to the mean profile, carries the promise of yielding more precise and robust clusters. In this paper, we propose a novel resampling based clustering algorithm for genes with replicated expression measurements. Assuming those replicates are exchangeable, we formulate the problem in the bootstrap framework, and aim to infer the consensus clustering based on the bootstrap samples of replicates. In our approach, we adopt the mixed effect model to accommodate the heterogeneous variances and implement a quasi-MCMC algorithm to conduct statistical inference. Experiments demonstrate that by taking advantage of the full replicate data, our algorithm produces more reliable clusters and has robust performance in diverse scenarios, especially when the data is subject to multiple sources of variance. PMID- 26671803 TI - An Optimization-Based Framework for the Transformation of Incomplete Biological Knowledge into a Probabilistic Structure and Its Application to the Utilization of Gene/Protein Signaling Pathways in Discrete Phenotype Classification. AB - Phenotype classification via genomic data is hampered by small sample sizes that negatively impact classifier design. Utilization of prior biological knowledge in conjunction with training data can improve both classifier design and error estimation via the construction of the optimal Bayesian classifier. In the genomic setting, gene/protein signaling pathways provide a key source of biological knowledge. Although these pathways are neither complete, nor regulatory, with no timing associated with them, they are capable of constraining the set of possible models representing the underlying interaction between molecules. The aim of this paper is to provide a framework and the mathematical tools to transform signaling pathways to prior probabilities governing uncertainty classes of feature-label distributions used in classifier design. Structural motifs extracted from the signaling pathways are mapped to a set of constraints on a prior probability on a Multinomial distribution. Being the conjugate prior for the Multinomial distribution, we propose optimization paradigms to estimate the parameters of a Dirichlet distribution in the Bayesian setting. The performance of the proposed methods is tested on two widely studied pathways: mammalian cell cycle and a p53 pathway model. PMID- 26671804 TI - Compression of Multiple DNA Sequences Using Intra-Sequence and Inter-Sequence Similarities. AB - Traditionally, intra-sequence similarity is exploited for compressing a single DNA sequence. Recently, remarkable compression performance of individual DNA sequence from the same population is achieved by encoding its difference with a nearly identical reference sequence. Nevertheless, there is lack of general algorithms that also allow less similar reference sequences. In this work, we extend the intra-sequence to the inter-sequence similarity in that approximate matches of subsequences are found between the DNA sequence and a set of reference sequences. Hence, a set of nearly identical DNA sequences from the same population or a set of partially similar DNA sequences like chromosome sequences and DNA sequences of related species can be compressed together. For practical compressors, the compressed size is usually influenced by the compression order of sequences. Fast search algorithms for the optimal compression order are thus developed for multiple sequences compression. Experimental results on artificial and real datasets demonstrate that our proposed multiple sequences compression methods with fast compression order search are able to achieve good compression performance under different levels of similarity in the multiple DNA sequences. PMID- 26671805 TI - Detecting Protein Complexes from Signed Protein-Protein Interaction Networks. AB - Identification of protein complexes is fundamental for understanding the cellular functional organization. With the accumulation of physical protein-protein interaction (PPI) data, computational detection of protein complexes from available PPI networks has drawn a lot of attentions. While most of the existing protein complex detection algorithms focus on analyzing the physical protein protein interaction network, none of them take into account the "signs" (i.e., activation-inhibition relationships) of physical interactions. As the "signs" of interactions reflect the way proteins communicate, considering the "signs" of interactions can not only increase the accuracy of protein complex identification, but also deepen our understanding of the mechanisms of cell functions. In this study, we proposed a novel Signed Graph regularized Nonnegative Matrix Factorization (SGNMF) model to identify protein complexes from signed PPI networks. In our experiments, we compared the results collected by our model on signed PPI networks with those predicted by the state-of-the-art complex detection techniques on the original unsigned PPI networks. We observed that considering the "signs" of interactions significantly benefits the detection of protein complexes. Furthermore, based on the predicted complexes, we predicted a set of signed complex-complex interactions for each dataset, which provides a novel insight of the higher level organization of the cell. All the experimental results and codes can be downloaded from http://mail.sysu.edu.cn/home/stsddq@mail.sysu.edu.cn/dai/others/SGNMF.zip. PMID- 26671806 TI - Explaining a Weighted DAG with Few Paths for Solving Genome-Guided Multi Assembly. AB - RNA-Seq technology offers new high-throughput ways for transcript identification and quantification based on short reads, and has recently attracted great interest. This is achieved by constructing a weighted DAG whose vertices stand for exons, and whose arcs stand for split alignments of the RNA-Seq reads to the exons. The task consists of finding a number of paths, together with their expression levels, which optimally explain the weights of the graph under various fitting functions, such as least sum of squared residuals. In (Tomescu et al. BMC Bioinformatics, 2013) we studied this genome-guided multi-assembly problem when the number of allowed solution paths was linear in the number of arcs. In this paper, we further refine this problem by asking for a bounded number k of solution paths, which is the setting of most practical interest. We formulate this problem in very broad terms, and show that for many choices of the fitting function it becomes NP-hard. Nevertheless, we identify a natural graph parameter of a DAG G, which we call arc-width and denote ?G?, and give a dynamic programming algorithm running in time O(W(k)?G?(k)(?G?+ k)n) , where n is the number of vertices and W is the maximum weight of G. This implies that the problem is fixed-parameter tractable (FPT) in the parameters W, ?G?, and k. We also show that the arc-width of DAGs constructed from simulated and real RNA-Seq reads is small in practice. Finally, we study the approximability of this problem, and, in particular, give a fully polynomial-time approximation scheme (FPTAS) for the case when the fitting function penalizes the maximum ratio between the weights of the arcs and their predicted coverage. PMID- 26671807 TI - In-silico Studies Show Potent Inhibition of HIV-1 Reverse Transcriptase Activity by a Herbal Drug. AB - Acquired immunodeficiency syndrome (AIDS) is a life threatening disease of the human immune system caused by human immunodeficiency virus (HIV). Effective inhibition of reverse transcriptase activity is a prominent, clinically viable approach for the treatment of AIDS. Few non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been approved by the United States Food and Drug Administration (US FDA) as drugs for AIDS. In order to enhance therapeutic options against AIDS we examined novel herbal compounds of 4-thiazolidinone and its derivatives that are known to have remarkable antiviral potency. Our molecular docking and simulation experiments have identified one such herbal molecule known as (5E)-3-(2-aminoethyl)-5-benzylidene-1, 3-thiazolidine-2,4-dione that may bind HIV-1RT with high affinity to cause noncompetitive inhibition. Results are also compared with other US FDA approved drugs. Long de novo simulations and docking study suggest that the ligand (5E)-3-(2-aminoethyl)-5 benzylidene-1, 3-thiazolidine-2,4-dione (CID: 1656714) has strong binding interactions with Asp113, Asp110, Asp185 and Asp186 amino acids, all of which belong to one or the other catalytic pockets of HIV-1RT. It is expected that these interactions could be critical in the inhibitory activity of the HIV-1RT. Therefore, this study provides an evidence for consideration of (5E)-3-(2 aminoethyl)-5-benzylidene-1, 3-thiazolidine-2,4-dione as a valuable natural molecule in the treatment and prevention of HIV-associated disorders. PMID- 26671808 TI - Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series. AB - Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles. PMID- 26671809 TI - PRBP: Prediction of RNA-Binding Proteins Using a Random Forest Algorithm Combined with an RNA-Binding Residue Predictor. AB - The prediction of RNA-binding proteins is an incredibly challenging problem in computational biology. Although great progress has been made using various machine learning approaches with numerous features, the problem is still far from being solved. In this study, we attempt to predict RNA-binding proteins directly from amino acid sequences. A novel approach, PRBP predicts RNA-binding proteins using the information of predicted RNA-binding residues in conjunction with a random forest based method. For a given protein, we first predict its RNA-binding residues and then judge whether the protein binds RNA or not based on information from that prediction. If the protein cannot be identified by the information associated with its predicted RNA-binding residues, then a novel random forest predictor is used to determine if the query protein is a RNA-binding protein. We incorporated features of evolutionary information combined with physicochemical features (EIPP) and amino acid composition feature to establish the random forest predictor. Feature analysis showed that EIPP contributed the most to the prediction of RNA-binding proteins. The results also showed that the information from the RNA-binding residue prediction improved the overall performance of our RNA-binding protein prediction. It is anticipated that the PRBP method will become a useful tool for identifying RNA-binding proteins. A PRBP Web server implementation is freely available at http://www.cbi.seu.edu.cn/PRBP/. PMID- 26671810 TI - PreProPath: An Uncertainty-Aware Algorithm for Identifying Predictable Profitable Pathways in Biochemical Networks. AB - Pathway analysis is a powerful approach to enable rational design or redesign of biochemical networks for optimizing metabolic engineering and synthetic biology objectives such as production of desired chemicals or biomolecules from specific nutrients. While experimental methods can be quite successful, computational approaches can enhance discovery and guide experimentation by efficiently exploring very large design spaces. We present a computational algorithm, Predictably Profitable Path (PreProPath), to identify target pathways best suited for engineering modifications. The algorithm utilizes uncertainties about the metabolic networks operating state inherent in the underdetermined linear equations representing the stoichiometric model. Flux Variability Analysis is used to determine the operational flux range. PreProPath identifies a path that is predictable in behavior, exhibiting small flux ranges, and profitable, containing the least restrictive flux-limiting reaction in the network. The algorithm is computationally efficient because it does not require enumeration of pathways. The results of case studies show that PreProPath can efficiently analyze variances in metabolic states and model uncertainties to suggest pathway engineering strategies that have been previously supported by experimental data. PMID- 26671811 TI - Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites. AB - With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/. PMID- 26671812 TI - Ribosome Flow Model on a Ring. AB - The asymmetric simple exclusion process (ASEP) is an important model from statistical physics describing particles that hop randomly from one site to the next along an ordered lattice of sites, but only if the next site is empty. ASEP has been used to model and analyze numerous multiagent systems with local interactions including the flow of ribosomes along the mRNA strand. In ASEP with periodic boundary conditions a particle that hops from the last site returns to the first one. The mean field approximation of this model is referred to as the ribosome flow model on a ring (RFMR). The RFMR may be used to model both synthetic and endogenous gene expression regimes. We analyze the RFMR using the theory of monotone dynamical systems. We show that it admits a continuum of equilibrium points and that every trajectory converges to an equilibrium point. Furthermore, we show that it entrains to periodic transition rates between the sites. We describe the implications of the analysis results to understanding and engineering cyclic mRNA translation in-vitro and in-vivo. PMID- 26671813 TI - Stable Gene Signature Selection for Prediction of Breast Cancer Recurrence Using Joint Mutual Information. AB - In this experiment, a gene selection technique was proposed to select a robust gene signature from microarray data for prediction of breast cancer recurrence. In this regard, a hybrid scoring criterion was designed as linear combinations of the scores that were determined in the mutual information (MI) domain and protein protein interactions network. Whereas, the MI-based score represents the complementary information between the selected genes for outcome prediction; and the number of connections in the PPI network between the selected genes builds the PPI-based score. All genes were scored by using the proposed function in a hybrid forward-backward gene-set selection process to select the optimum biomarker-set from the gene expression microarray data. The accuracy and stability of the finally selected biomarkers were evaluated by using five-fold cross-validation (CV) to classify available data on breast cancer patients into two cohorts of poor and good prognosis. The results showed an appealing improvement in the cross-dataset accuracy in comparison with similar studies whenever we applied a primary signature, which was selected from one dataset, to predict survival in other independent datasets. Moreover, the proposed method demonstrated 58-92 percent overlap between 50-genes signatures, which were selected from seven independent datasets individually. PMID- 26671814 TI - Synchronization of Asynchronous Switched Boolean Network. AB - In this paper, the complete synchronizations for asynchronous switched Boolean network with free Boolean sequence controllers and close-loop controllers are studied. First, the basic asynchronous switched Boolean network model is provided. With the method of semi-tensor product, the Boolean dynamics is translated into linear representation. Second, necessary and sufficient conditions for ASBN synchronization with free Boolean sequence control and close loop control are derived, respectively. Third, some illustrative examples are provided to show the efficiency of the proposed methods. PMID- 26671815 TI - A Computational Approach Using Ratio Statistics for Identifying Housekeeping Genes from cDNA Microarray Data. AB - We predict housekeeping genes from replicate microarray gene expression data of human lymphoblastoid cells and liver tissue with outliers removed using a scoring scheme, by an algorithm based on statistical hypothesis testing, assuming that such genes are constitutively expressed. A few predicted genes were examined and found to be housekeeping. PMID- 26671816 TI - A Novel Scoring Based Distributed Protein Docking Application to Improve Enrichment. AB - Molecular docking is a computational technique which predicts the binding energy and the preferred binding mode of a ligand to a protein target. Virtual screening is a tool which uses docking to investigate large chemical libraries to identify ligands that bind favorably to a protein target. We have developed a novel scoring based distributed protein docking application to improve enrichment in virtual screening. The application addresses the issue of time and cost of screening in contrast to conventional systematic parallel virtual screening methods in two ways. Firstly, it automates the process of creating and launching multiple independent dockings on a high performance computing cluster. Secondly, it uses a Naive Bayes scoring function to calculate binding energy of un-docked ligands to identify and preferentially dock (Autodock predicted) better binders. The application was tested on four proteins using a library of 10,573 ligands. In all the experiments, (i). 200 of the 1,000 best binders are identified after docking only ~14 percent of the chemical library, (ii). 9 or 10 best-binders are identified after docking only ~19 percent of the chemical library, and (iii). no significant enrichment is observed after docking ~70 percent of the chemical library. The results show significant increase in enrichment of potential drug leads in early rounds of virtual screening. PMID- 26671817 TI - Model Order and Identifiability of Non-Linear Biological Systems in Stable Oscillation. AB - The paper presents a theoretical result that clarifies when it is at all possible to determine the nonlinear dynamic equations of a biological system in stable oscillation, from measured data. As it turns out the minimal order needed for this is dependent on the minimal dimension in which the stable orbit of the system does not intersect itself. This is illustrated with a simulated fourth order Hodgkin-Huxley spiking neuron model, which is identified using a non-linear second order differential equation model. The simulated result illustrates that the underlying higher order model of the spiking neuron cannot be uniquely determined given only the periodic measured data. The result of the paper is of general validity when the dynamics of biological systems in stable oscillation is identified, and illustrates the need to carefully address non-linear identifiability aspects when validating models based on periodic data. PMID- 26671819 TI - ENDEAVOR to change treatment for multiple myeloma? PMID- 26671820 TI - Management of ankle injuries. PMID- 26671821 TI - G-quadruplex DNA structures can interfere with uracil glycosylase activity in vitro. AB - Genome sequences that contain tandem repeats of guanine can form stable four stranded structures known as G-quadruplex, or G4 DNA. While the molecular mechanisms are not fully defined, such guanine-rich loci are prone to mutagenesis and recombination. Various repair pathways function to reduce the potential for genome instability by correcting base damage and replication errors; however, it is not yet fully defined how well these processes function at G4 DNA. One frequent form of base damage occurs from cytidine deamination, resulting in deoxyuracil and UG mismatches. In duplex and single-stranded DNA, uracil bases are recognised and excised by uracil glycosylases. Here, we tested the efficiency of uracil glycosylase activity in vitro on uracil bases located directly adjacent to guanine repeats and G4 DNA. We show that uracil excision by bacterial UDG and human hUNG2 is reduced at uracils positioned directly 5' or 3' of a guanine tetrad. Control reactions using oligonucleotides disrupted for G4 formation or reaction conditions that do not favour G4 formation resulted in full uracil excision activity. Based on these in vitro results, we suggest that folding of guanine-rich DNA into G4 DNA results in a DNA conformation that is resistant to uracil glycosylase-initiated repair and this has the potential to increase the risk of instability at guanine repeats in the genome. PMID- 26671822 TI - A tailored approach to regional nodal irradiation. AB - Regional nodal irradiation for breast cancer has recently been shown to improve disease-free survival, distant disease-free survival, and breast-related mortality but is associated with morbidity. A tailored approach adding regional nodal irradiation only to patients with involvement of the internal mammary nodes is improving prognosis while minimizing morbidity. PMID- 26671823 TI - The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. AB - Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is a secreted glycoprotein that belongs to a group of transporters of small lipophilic molecules in circulation. LCN2 has been recently characterized as an adipose-derived cytokine. This adipokine is believed to bind small substances, such as steroids and lipopolysaccharides, and has been reported to have roles in the induction of apoptosis in hematopoietic cells, transport of fatty acids and iron, modulation of inflammation, and metabolic homeostasis. Recently, LCN2 has emerged as a useful biomarker and rheumatic diseases. This review provides an overview of LCN2 in inflammation, immunity, and metabolism. PMID- 26671826 TI - Inflammation, High-sensitivity C-reactive Protein, and Persistent Patent Ductus Arteriosus in Preterm Infants. PMID- 26671818 TI - Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. AB - BACKGROUND: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. METHODS: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1.3 mg/m(2); intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. FINDINGS: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11.9 months (IQR 9.3-16.1) in the carfilzomib group and 11.1 months (8.2-14.3) in the bortezomib group. Median progression-free survival was 18.7 months (95% CI 15.6 not estimable) in the carfilzomib group versus 9.4 months (8.4-10.4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0.53 [95% CI 0.44-0.65]; p<0.0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). INTERPRETATION: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. FUNDING: Onyx Pharmaceuticals, Inc., an Amgen subsidiary. PMID- 26671825 TI - Hyperuricemia and nonalcoholic fatty liver disease: from bedside to bench and back. AB - Uric acid is the end product of dietary or endogenous purines degradation, and hyperuricemia is one of the most common metabolic disorders. It has been widely accepted that hyperuricemia increases risks of gout, cardiovascular diseases, and type 2 diabetes. A growing body of evidence, comprising a great deal of cross sectional studies and several prospective ones, also indicates that hyperuricemia is associated with increased prevalence, incidence and disease severity of non alcoholic fatty liver disease (NAFLD). On the contrary, NAFLD can predict hyperuricemia as well. However, no causal relationship can be drawn from this point. With a well-established relationship between uric acid and NAFLD prevalence as well as disease severity in addition to the role of potential therapeutic target, the prognostic role of uric acid is also worth investigating. Further studies should focus on the prospective role of uric acid on NAFLD progression and its underlying mechanisms, as well as its clinical implications. PMID- 26671827 TI - Synthetic surgical meshes used in abdominal wall surgery: Part I-materials and structural conformation. AB - Surgical implants are commonly used in abdominal wall surgery for hernia repair. Many different prostheses are currently offered to surgeons, comprising permanent synthetic polymer meshes and biologic scaffolds. There is a wide range of synthetic meshes currently available on the market with differing chemical compositions, fiber conformations, and mesh textures. These chemical and structural characteristics determine a specific biochemical and mechanical behavior and play a crucial role in guaranteeing a successful post-operative outcome. Although an increasing number of studies report on the structural and mechanical properties of synthetic surgical meshes, nowadays there are no consistent guidelines for the evaluation of mechanical biocompatibility or common criteria for the selection of prostheses. The aim of this work is to review synthetic meshes by considering the extensive bibliography documentation of their use in abdominal wall surgery, taking into account their material and structural properties, in Part I, and their mechanical behavior, in Part II. The main materials available for the manufacture of polymeric meshes are described, including references to their chemical composition, fiber conformation, and textile structural properties. These characteristics are decisive for the evaluation of mesh-tissue interaction process, including foreign body response, mesh encapsulation, infection, and adhesion formation. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 689-699, 2017. PMID- 26671828 TI - Sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses. AB - It was shown previously that human saliva has higher antiviral activity against human influenza viruses than against H5N1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic acid-containing molecules. To further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza A and B virus, pandemic H1N1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and chicken saliva. Human saliva showed higher hemagglutination inhibition (HI) and neutralization (NT) titers against seasonal influenza A virus and the pandemic H1N1 viruses than against influenza B virus and most avian influenza viruses, except for H9N2 and H12N9 avian influenza viruses, which showed high HI and NT titers. To understand the nature of sialic acid-containing anti-influenza factors in human saliva, alpha2,3- and alpha2,6 linked sialic acid was measured in human saliva samples using a lectin binding and dot blot assay. alpha2,6-linked sialic acid was found to be more abundant than alpha2,3-linked sialic acid, and a seasonal H1N1 influenza virus bound more efficiently to human saliva than an H5N1 virus in a dot blot analysis. These data indicated that human saliva contains the sialic acid type corresponding to the binding preference of seasonal influenza viruses. PMID- 26671829 TI - Study of antibody repertoires to the CD4 binding site of gp120 of a Chinese HIV-1 infected elite neutralizer, using 454 sequencing and single-cell sorting. AB - Broadly neutralizing antibodies (NAbs) against the CD4 binding site of HIV gp120 (CD4bs) have provided important information for vaccine design. In this study, we combined deep sequencing and single memory B cell sorting to isolate CD4bs directed NAbs from a Chinese HIV-1-infected elite neutralizer. We first performed 454 pyrosequencing to capture the IGHV1, IGKV, and IGLV germline gene families. IGHV1-2*02, the heavy chain germline V gene (VH) of the CD4bs-directed bNAb VRC01, was found to have a relatively low somatic mutation rate. When an identity/divergence plot was used to interrogate the 454 sequencing data, no VRC01-like sequences were found within the dataset. We next used a pair of CD4bs specific probes (RSC3/DeltaRSC3) to sort the B cells from this Chinese donor and identified a CD4bs-directed Ab that showed limited neutralization capability. Interestingly, the VH gene of this weak NAb belongs to the IGHV5-51 lineage, with a somatic mutation rate of 7.99 %. Our study thus demonstrates that CD4bs directed NAbs can be produced by rearrangement from other VH genes, such as IGHV5 51 in this donor, rather than IGHV1-2*02. The 454 sequencing data and NAb obtained from this study will provide useful insights into the CD4bs-directed B cell response during HIV-1 infection as well as the diversity of neutralizing antibodies. PMID- 26671831 TI - The Effect of High- and Low-Damping Prosthetic Foot Structures on Knee Loading in the Uninvolved Limb Across Different Walking Speeds. AB - Lower limb amputation has been associated with secondary impairments such as knee osteoarthritis in the uninvolved limb. Greater knee loading in the frontal plane has been related to severity and rate of progression in knee osteoarthritis. Reduced push-off work from the involved limb can increase uninvolved limb knee loading. However, little is known about specific effects that prosthetic foot damping may have on uninvolved limb loading. We hypothesized that uninvolved limb peak knee internal abduction moment (IAM) and loading rates would be greater when using a high-damping foot compared with a low-damping foot, across walking speeds. Eight healthy, young subjects walked in a prosthesis simulator boot using the experimental feet. Greater uninvolved limb first peak IAM (+16% in fast speed, P = .002; +11% in slow speed, P = .001) and loading rates (+11% in fast speed, P = .003) were observed when using the high-damping foot compared with low damping foot. Within each foot, uninvolved limb first peak IAM and loading rates had a trend to increase with increased walking speed. These findings suggest that damping properties of prosthetic feet are related to uninvolved limb peak knee IAM and loading rates. PMID- 26671830 TI - Interaction of diuron to human serum albumin: Insights from spectroscopic and molecular docking studies. AB - This investigation was undertaken to determine the interaction of diuron with human serum albumin (HSA) was studied by monitoring the spectral behavior of diuron-HSA system. The fluorescence of HSA at 340 nm excited at 230 nm was obviously quenched by diuron due to dynamic collision and the quenching constant was of the order of 10(4) L mol(-1) at 310 K. However, no fluorescence quenching was observed when excited at 280 nm. Thermodynamic investigations revealed that the combination between diuron and HSA was entropy driven by predominantly hydrophobic interactions. The binding of diuron induced the drastic reduction in alpha-helix conformation and the significant enhancement in beta-turn conformation of HSA. In addition, both sites marker competition study and molecular modeling simulation evidenced the binding of diuron to HSA primarily took place in subdomain IIIA (Sudlow's site II). PMID- 26671832 TI - An unusual highly emissive water-soluble iridium lissamine-alanine complex and its use in a molecular logic gate. AB - The interaction of iridium(iii) with a new lissamine rhodamine B sulfonyl derivative, bearing alanine as a building block, (1) with an orange emission in water results in a green highly emissive Ir@1 complex at room temperature. The new Ir@1 complex can sense the toxic Hg(2+) metal ion and cysteine. Based on such properties, a new sophisticated molecular logic gate with three inputs was designed. PMID- 26671833 TI - How mothers mediate the social integration of their children conceived of forced marriage within the Lord's Resistance Army. AB - This article aims to understand how formerly abducted young mothers mediate the social integration of their children conceived of forced marriage and sexual violence within the Lord's Resistance Army (LRA) in northern Uganda. Interviews and photographic methods were used in six Internally Displaced Persons Camps in northern Uganda. This article draws on data derived from ten mothers of thirteen children who were conceived in the LRA, five boys and eight girls. The analytic approach used was Interpretive Phenomenological Analysis (Smith & Osborn, 2008). The analysis identified turning points of sites of action where young formerly abducted mothers used diverse strategies to support the reintegration of their children born or conceived within the LRA. Six key turning points are identified, these are (a) participating in rituals and ceremonies, (b) naming, (c) adapting to changing family structures, (d) responding to discrimination against boys (e) managing disclosure and (f) sharing positive memories and identities. Formerly abducted young mothers mediate the social integration of their children by engaging in strategies to support and foster their wellbeing and social relationships. However, the contexts in which they are operating are highly constrained and the relational identities of children born in the LRA are fluid and potentially insecure within communities of return. Implications for policy and programming are discussed. PMID- 26671835 TI - Does optimal access to dental care counteract the oral health-related quality of life social gradient? AB - BACKGROUND: The aim of this study was to determine if an oral health-related quality of life (OHRQoL) social gradient existed when Australian Defence Force (ADF) members have universal and optimal access to dental care. METHODS: A nominal roll included 4089 individuals who were deployed to the Solomon Islands as part of Operation ANODE and a comparison group of 4092 ADF personnel frequency matched to the deployed group on gender, age group and service type, from which 500 deployed and 500 comparison individuals were randomly selected. The dependent variables were the OHIP-14 summary measures. Rank was used to determine socioeconomic status. The demographic variables selected were: gender and age. RESULTS: The response rate was 44%. Of the individual OHIP-14 items, being self conscious, painful aching and having discomfort when eating were the most common problems. Mean OHIP-14 severity was 2.8. In bivariate analysis, there was not a significant difference in mean OHIP-14 severity (p = 0.52) or frequency of OHIP 14 impacts (p = 0.57) by military rank. There was a significant increasing OHIP 14 extent score from commissioned officer to non-commissioned officer to other ranks (0.07, 0.19, 0.40, p = 0.03). CONCLUSIONS: Even with optimal access to dental care, there was an OHRQoL social gradient between military ranks in the ADF. PMID- 26671834 TI - Alpha-2 adrenoceptor agonists as adjuncts to peripheral nerve blocks in children: a meta-analysis. AB - BACKGROUND: Adult meta-analyses have verified that adjunct use of alpha-2 adrenoceptor agonists (A2AA) together with local anesthetics (LA) will prolong the duration of peripheral nerve blocks. The standard use of A2AAs for peripheral nerve blockade has recently been recommended also in children, but the evidence base in support of this suggestion has to date been equivocal. The purpose of this meta-analysis was to produce evidence-based data regarding the effect in children. METHODS: Following a thorough literature search, five randomized controlled trials were included in a meta-analysis. Raw data from all studies were gathered and aggregated into patients randomized to receive plain LA (Group PLA) or LA mixed with either adjunct clonidine or dexmedetomidine (Group ADJ). The main outcome parameter was block duration (time to first administration of supplemental analgesic based on predetermined pain scores) analyzed by survival statistics. The total number of supplemental analgesic doses during the first 24 postoperative hours and serious side effects were included as secondary outcomes. RESULTS: Pooling of the study data generated 141 patients in Group PLA and 142 patients in Group ADJ (overall n = 283; age: 0.8-13 years; weight 8-47 kg). Block duration was significantly prolonged (9.75 h vs 3.75 h) compared to the use of plain LA. Survival statistics verified a beneficial effect of using adjunct A2AAs [the log rank (Mantel-Cox) test (P = 0.0078), Gehan-Breslow-Wilcoxon test (P = 0.0027), and hazard ratio (1.653; 95% CI: 1.142 to 2.395)]. The number of patients that needed >= 2 doses of supplemental analgesics was higher in Group PLA (n = 19) compared to Group ADJ (n = 6) (P = 0.0088). No serious side effects were reported. CONCLUSION: This meta-analysis provides evidence-based support for the use of adjunct alpha-2 adrenoceptor agonists when performing peripheral nerve blocks in children. PMID- 26671836 TI - Activating a Low Overpotential CO2 Reduction Mechanism by a Strategic Ligand Modification on a Ruthenium Polypyridyl Catalyst. AB - The introduction of a simple methyl substituent on the bipyridine ligand of [Ru(tBu3 tpy)(bpy)(NCCH3 )](2+) (tBu3 tpy=4,4',4''-tri-tert-butyl-2,2':6',2'' terpyridine; bpy=2,2'-bipyridine) gives rise to a highly active electrocatalyst for the reduction of CO2 to CO. The methyl group enables CO2 binding already at the one-electron reduced state of the complex to enter a previously not accessible catalytic cycle that operates at the potential of the first reduction. The complex turns over with a Faradaic efficiency close to unity and at an overpotential that is amongst the lowest ever reported for homogenous CO2 reduction catalysts. PMID- 26671837 TI - Patch Testing with Main Sensitizers Does Not Detect All Cases of Contact Allergy to Oxidized Lavender Oil. AB - Lavender oil is an essential oil obtained from lavender (Lavendula angustifolia). The main components linalool and linalyl acetate have been shown to autoxidize in contact with oxygen in the air, forming sensitizing hydroperoxides. Patients with suspected allergic contact dermatitis were consecutively patch-tested with oxidized lavender oil 6% pet., oxidized linalyl acetate 6% pet., and oxidized linalool 6% pet. to investigate the frequency of contact allergy to oxidized lavender oil, and the pattern of concomitant reactions to oxidized linalool and oxidized linalyl acetate. Positive reactions to oxidized lavender oil were found in 2.8% of the patients. Among those, 56% reacted to oxidized linalool and/or oxidized linalyl acetate, while 52% reacted to the fragrance markers of the baseline series. Oxidized lavender oil showed among the highest frequencies of contact allergy to studied essential oils. A well-standardized preparation of oxidized lavender oil could be a useful tool for diagnosis of contact allergy to fragrances. PMID- 26671838 TI - The anatomy of E-Learning tools: Does software usability influence learning outcomes? AB - Reductions in laboratory hours have increased the popularity of commercial anatomy e-learning tools. It is critical to understand how the functionality of such tools can influence the mental effort required during the learning process, also known as cognitive load. Using dual-task methodology, two anatomical e learning tools were examined to determine the effect of their design on cognitive load during two joint learning exercises. A.D.A.M. Interactive Anatomy is a simplistic, two-dimensional tool that presents like a textbook, whereas Netter's 3D Interactive Anatomy has a more complex three-dimensional usability that allows structures to be rotated. It was hypothesized that longer reaction times on an observation task would be associated with the more complex anatomical software (Netter's 3D Interactive Anatomy), indicating a higher cognitive load imposed by the anatomy software, which would result in lower post-test scores. Undergraduate anatomy students from Western University, Canada (n = 70) were assessed using a baseline knowledge test, Stroop observation task response times (a measure of cognitive load), mental rotation test scores, and an anatomy post-test. Results showed that reaction times and post-test outcomes were similar for both tools, whereas mental rotation test scores were positively correlated with post-test values when students used Netter's 3D Interactive Anatomy (P = 0.007), but not when they used A.D.A.M. Interactive Anatomy. This suggests that a simple e learning tool, such as A.D.A.M. Interactive Anatomy, is as effective as more complicated tools, such as Netter's 3D Interactive Anatomy, and does not academically disadvantage those with poor spatial ability. Anat Sci Educ 9: 378 390. (c) 2015 American Association of Anatomists. PMID- 26671839 TI - Fixed Implant Supported Rehabilitation of Partially Edentulous Posterior Maxilla in a Patient With Systemic Scleroderma: A Case Report. AB - Systemic Scleroderma (SSc) is an autoimmune disease that affects connective tissue, resulting in hardening skin, reduced vascular perfusion, gingival fibrosis, enlarged periodontal ligament, xerostomia, and trigeminal neuralgia. Secondary effects, including reduced oral opening and reduced manual dexterity may exacerbate the primary effects. Severe bone loss and premature tooth loss are common eventualities of SSc. Removable prosthetics can be a tedious option for these patients as the progression of the disease often leads to the impossibility of obtaining minimal standards of care, including stability, retention, and hygienic maintainability. Implant treatment of patients with Systemic Scleroderma is poorly documented, and common medications used to treat SSc have been considered relative contraindications to the prescription of dental implant therapy. This report describes 1 case after 2 years in function, where dental implants were successfully utilized to offer definitive fixed rehabilitation to a patient with SSc. PMID- 26671840 TI - Controlling false discoveries in genome scans for selection. AB - Population differentiation (PD) and ecological association (EA) tests have recently emerged as prominent statistical methods to investigate signatures of local adaptation using population genomic data. Based on statistical models, these genomewide testing procedures have attracted considerable attention as tools to identify loci potentially targeted by natural selection. An important issue with PD and EA tests is that incorrect model specification can generate large numbers of false-positive associations. Spurious association may indeed arise when shared demographic history, patterns of isolation by distance, cryptic relatedness or genetic background are ignored. Recent works on PD and EA tests have widely focused on improvements of test corrections for those confounding effects. Despite significant algorithmic improvements, there is still a number of open questions on how to check that false discoveries are under control and implement test corrections, or how to combine statistical tests from multiple genome scan methods. This tutorial study provides a detailed answer to these questions. It clarifies the relationships between traditional methods based on allele frequency differentiation and EA methods and provides a unified framework for their underlying statistical tests. We demonstrate how techniques developed in the area of genomewide association studies, such as inflation factors and linear mixed models, benefit genome scan methods and provide guidelines for good practice while conducting statistical tests in landscape and population genomic applications. Finally, we highlight how the combination of several well calibrated statistical tests can increase the power to reject neutrality, improving our ability to infer patterns of local adaptation in large population genomic data sets. PMID- 26671841 TI - Hartmut Lichtenthaler: an authority on chloroplast structure and isoprenoid biochemistry. AB - We pay tribute to Hartmut Lichtenthaler for making important contributions to the field of photosynthesis research. He was recently recognized for ground-breaking discoveries in chloroplast structure and isoprenoid biochemistry by the Rebeiz Foundation for Basic Research (RFBR; http://vlpbp.org/ ), receiving a 2014 Lifetime Achievement Award for Photosynthesis. The ceremony, held in Champaign, Illinois, was attended by many prominent researchers in the photosynthesis field. We provide below a brief note on his education, and then describe some of the areas in which Hartmut Lichtenthaler has been a pioneer. PMID- 26671842 TI - Treatment of LS174T colorectal cancer stem-like cells with n-3 PUFAs induces growth suppression through inhibition of survivin expression and induction of caspase-3 activation. AB - PURPOSE: Colorectal cancer stem cells (CCSCs) are thought to contribute to tumor initiation, progression, metastasis, chemo-resistance and therapy failure. Therefore, assessment of the effectiveness of agents with anti-proliferative activities against CCSCs is warranted. Several studies have shown that different tumorigenic steps, ranging from initiation to metastasis, can be affected by n-3 polyunsaturated fatty acids (PUFAs). Here, we evaluated the effects of the PUFA components docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), alone or in combination, on LS174T cells that serve as a model for colorectal cancer initiating cells with stem cell-like properties. METHODS: LS174T cells were treated with 50, 100 and 150 MUM DHA and EPA, or equal mixtures of DHA/EPA (i.e., 25/25, 50/50 and 75/75 MUM), after which cell number, viability, growth inhibition, survivin expression, caspase-3 activation and apoptotic rate were evaluated. RESULTS: We found that treatment of LS174T cells with increasing PUFA concentrations significantly increased growth inhibition in a dose- and time dependent manner. After a 72 h treatment with 150 MUM DHA and EPA, or their combination (75/75 MUM), growth rates were inhibited by 80.3 +/- 5.5%, 79.3 +/- 5% and 71.1 +/- 1%, respectively, compared to untreated cells. We also found that treatment for 48 h with 100 MUM DHA and EPA, or their combination (50/50 MUM), resulted in 2.9-, 3- and 2.6-fold increases in caspase-3 activation, as well as 54, 62.4 and 100% decreases in survivin mRNA expression levels, respectively, compared to untreated cells. Low survivin mRNA levels combined with high caspase 3 activity levels were found to correlate with a higher growth inhibition in PUFA treated cells. DHA appears to be a more potent growth inhibitor than EPA and the DHA/EPA combination. An increase in the number of apoptotic cells (early + late), ranging from 12.9 to 44.7%, was observed with increasing DHA doses. CONCLUSION: From our data we conclude that PUFAs induce growth inhibition via targeting survivin expression in LS174T cells, which serve as a model for CCSCs. PMID- 26671843 TI - Polypharmacy among the elderly in the Republic of Srpska: extent and implications for the future. AB - The prescribing of medicines is a fundamental component of care for the elderly; however, there is increasing concern with polypharmacy and its impact on morbidity, mortality and costs. As a result, long-term prescription-medicine use and the prevalence of polypharmacy in the elderly in the Republic of Srpska were analyzed. The findings were subsequently used to suggest potential future measures. A retrospective study of all elderly patients during 2005-2010 stratified by age group (three groups), sex and long-term medicine use was performed. Polypharmacy (five or more medicines) increased from 1.4% of the elderly taking medicines long-term to 3.6% by 2010, with 53.6% of elderly taking two or more medicines long-term. The most prevalent diseases were cardiovascular diseases and diabetes. Most prescriptions were in accordance with recent guidelines; however, there was a concern with appreciable prescribing of digoxin and aminophylline. Whilst polypharmacy rates are low in the Republic, the increasing rate is a concern. Further studies are planned. PMID- 26671844 TI - Immunoexpression of growth factors and receptors in polymorphous low-grade adenocarcinoma. AB - BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignant tumor that usually arises in the minor salivary glands. Growth factors are cell secreted peptides that regulate biological processes such as growth, proliferation, and differentiation. In salivary gland tumors, immunoexpression of growth factors and their receptors is associated with cell proliferation, malignant transformation, and tumor invasion. This study analyzed the expression of growth factors and receptors in PLGA, in other to better understand the mechanisms involved in the process of neoplastic cell proliferation and tumor progression. METHODS: The expression of growth factors FGF-2, PDGF-A, PDGF-B and receptors FGFR-1, FGFR-2, PDGFR-alpha, and EGFR was analyzed in 24 PLGA samples in comparison with normal salivary glands, by immunohistochemistry. A semi quantitative analysis determined cell positivity in all stained sections. Scores were assigned according to percentage of reactive cells: score 0 < 10%; score 1 10 to 25%; score 2-25% to 50%; score 3->50%. The level of significance was set at 5%. RESULTS: Most of the growth factors and receptors, apart from FGFR-2, were significantly reactive in PLGA. Comparing to salivary acini, all of the reactive growth factors and receptors were significantly stronger in PLGA. Comparing to salivary ducts, the expression of FGF-2, PDGF-B, FGFR-1, and EGFR was significantly stronger in the nuclei and/or cytoplasm of the neoplastic cells. CONCLUSIONS: The increased expression of the growth factors and receptors in the PLGA, compared to normal salivary glands, may be related to cell proliferation, somehow participating in the oncogenic process. PMID- 26671845 TI - Ethical Standards in Sport and Exercise Science Research: 2016 Update. PMID- 26671846 TI - Dehydrogenative Homocoupling of Alkyl Chains on Cu(110). AB - Through the interplay of high-resolution scanning tunneling microscopy imaging and density functional theory calculations, the stepwise dehydrogenative homocoupling of alkyl chains on Cu(110) is demonstrated, proceeding from the intact chain, via the dehydrogenative intermediates, to the formation of the divers final coupling products. PMID- 26671847 TI - The role of reactive oxygen species in the antibacterial photodynamic treatment: photoinactivation vs proliferation. AB - Low-level light/low concentration of reactive oxygen species (ROS) may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of stimulation of bacterial cell proliferation during photodynamic therapy (PDT). In this study, PDT with different doses of 809-nm laser and indocyanine green (ICG) was investigated in vitro for safe bactericidal application. The combined effect of laser doses with ICG concentrations were examined on Pseudomonas aeruginosa in vitro. Data showed that low energy dose and ICG concentration caused bacterial cell proliferation. When these parameters were increased high enough, photoinactivation of the bacteria was achieved. Energy dose and photosensitizer concentration ranges at which proliferation, cell death or neither observed were determined. Furthermore, l-histidine was used as a scavenger of ROS to block the mechanism of biostimulation and cell killing. It inhibited proliferation when laser dose and ICG concentrations were low. It also inhibited cell killing when dose and concentration were high. Data showed that mechanisms of proliferation and cell killing depend on the amount of ROS and antibacterial photodynamic treatment have serious biostimulative risk. Effective range might need to be determined before any therapeutic usage. The risk seems to exist specifically at lower energy doses and photosensitizer concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The main purpose in antibacterial photodynamic therapy (PDT) is to kill the micro-organisms that cannot be destroyed by conventional methods. Low-level light and/or low concentration of reactive oxygen species may trigger some biochemical pathways that lead to cell proliferation. Thus, there is a risk of bacterial cell proliferation during PDT. In this study we report that PDT with ICG application can induce biostimulation when laser dose and photosensitizer concentration are not optimized properly. Therefore, optimum dosimetry in PDT possesses great importance in the treatment of wounds infected by antibiotic-resistant bacteria. PMID- 26671849 TI - High-flow nasal oxygen and standard oxygen in the emergency department: Clarifying comparison. PMID- 26671850 TI - The strong but nonspecific relationship between 18F-FDG uptake in the lower extremity veins and venous thromboembolism. AB - Venous thromboembolism (VTE) can present as deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). In fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT, 18F-FDG activity along the deep veins of the lower extremities (LE) is often observed and, unless it is associated with focal intense activity, is not considered abnormal. However, anecdotally it has been associated with the placement of an inferior vena cava filter. In this short paper we intend to investigate this association. We found 10 patients who were investigated in the vascular laboratory by means of either LE or upper-extremity duplex or a chest computed tomography with PE protocol, or who had undergone the placement of an inferior vena cava filter between 27 April 2010 and 7 January 2013 and who had also undergone one or more 18F-FDG-PET scan(s) that included the LE. Seventeen patients without venous 18F-FDG uptake were added as controls. 18F-FDG uptake visualized in the LE was scored as the number of positive LE veins and the extent of the radiotracer uptake. The time intervals between the VTE event and the 18F FDG-PET scan(s) were recorded. The time intervals between the most remote and the closest 18F-FDG-PET before a VTE event averaged 79 +/- 101 and 49 +/- 82 days, respectively, and the closest and the most remote 18F-FDG-PET after the VTE event averaged 58 +/- 50 and 122 +/- 124 days. The extent of uptake in the LE veins averaged 7 +/- 2 for the patients with an acute DVT on LE duplex and 5 +/- 3 for those with negative or chronic DVT on LE duplex (P=nonsignificant). Two patients (n=3 and 10) were negative for VTE events and had an extent of 0. The number of positive events correlated slightly with the extent of venous uptake (r=0.69). The 17 control patients without venous uptake on 18F-FDG-PET had no history of VTE. There was an association between LE venous uptake of 18F-FDG and risk for VTE. The association was not related to the location of the VTE, nor to the timing of the VTE. PMID- 26671848 TI - Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction. AB - Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction. PMID- 26671851 TI - Cardiac neuroendocrine tumour metastases: case reports and review of the literature. AB - BACKGROUND: Most neuroendocrine tumours (NETs) metastasize to the liver, lymph nodes and, although less frequently, to the bone. The heart is a rare localization for NET metastases. METHODS: With the introduction of the Ga DOTATATE PET/computed tomography (CT) in our hospital as a new diagnostic method for imaging neuroendocrine tumours, more rare metastatic localizations are being found. We present six cases of patients with cardiac NET metastases detected by Ga-DOTATATE PET/CT. Also, a review of literature is presented on case reports of cardiac NET metastases in patients detected by somatostatin receptor imaging, including In-Pentetreotide single photon emission computed tomography/CT, Ga DOTATATE PET/CT, Ga-DOTANOC PET/CT or Ga-DOTATOC PET/CT. RESULTS AND CONCLUSION: Most patients with cardiac NET metastases have extensive metastatic disease. The cardiac metastases are often asymptomatic. PMID- 26671853 TI - Hunt dismisses BMJ editor's claims that he misused weekend mortality data. PMID- 26671852 TI - Prediction of iodine-131 biokinetics and radiation doses from therapy on the basis of tracer studies: an important question for therapy planning in nuclear medicine. AB - OBJECTIVES: This study aimed to present a comparison of iodine-131 (I) biokinetics and radiation doses to red-marrow (rm) and whole-body (wb), following the administration of tracer and therapeutic activities, as a means of confirming whether I clearance and radiation doses for therapy procedures can be predicted by tracer activities. METHODS: Eleven differentiated thyroid cancer patients were followed after receiving tracer and therapeutic I activity. Whole-body I clearance was estimated using radiation detectors and OLINDA/EXM software was used to calculate radiation doses to rm and wb. RESULTS AND DISCUSSION: Tracer I activity of 86 (+/-14) MBq and therapeutic activity of 8.04 (+/-1.18) GBq were administered to patients, thereby producing an average wb I effective half-time and residence time of, respectively, 13.51 (+/-4.05) and 23.13 (+/-5.98) h for tracer activities and 13.32 (+/-3.38) and 19.63 (+/-4.77) h for therapy. Radiation doses to rm and wb were, respectively, 0.0467 (+/-0.0208) and 0.0589 (+/-0.0207) mGy/MBq in tracer studies and 0.0396 (+/-0.0169) and 0.0500 (+/ 0.0163) mGy/MBq in therapy. Although the differences were not considered statistically significant between averages, those between the values of effective half-times (P=0.906), residence times (P=0.145), and radiation doses to rm (P=0.393) and to wb (P=0.272), from tracer and therapy procedures, large differences of up to 80% in wb I clearance, and up to 50% in radiation doses were observed when patients were analyzed individually, thus impacting on the total amount of I activity calculated to be safe for application in individual therapy. CONCLUSION: I biokinetics and radiation doses to rm and wb in therapy procedures are well predicted by diagnostic activities when average values of a group of patients are compared. Nonetheless, when patients are analyzed individually, significant differences may be encountered, thus implying that nuclear medicine therapy-planning requires due consideration of changes in individual patient-body status from initial tracer to final therapy procedures to thus provide appropriate adjustments in therapeutic activities. PMID- 26671854 TI - Introduction: Toward a Psychoanalytic Psychology of Repair after Gross Human Rights Abuses. PMID- 26671855 TI - Psychological Repair: The Intersubjective Dialogue of Remorse and Forgiveness in the Aftermath of Gross Human Rights Violations. AB - The possibility of psychological repair after mass trauma is considered here in the context of the global trend of dialogue between survivors and perpetrators in the aftermath of mass atrocities. Stories of remorse and forgiveness illustrate and allow reflection on the last two decades' experience in dealing with the past, as exemplified by truth commissions in countries like South Africa and Rwanda. Three aspects of this experience are stressed. First, it is argued that the Truth and Reconciliation Commission (TRC) of South Africa was a unique dialogic space that enabled the emergence of new subjectivities in the encounter between survivors and perpetrators. Second, concepts of intersubjectivity are used to explore how a psychoanalytic perspective might contribute to understanding the process of trauma testimony, and to examine the different ways in which empathy plays out in survivors' and perpetrators' responses as witnesses to trauma testimony. A key element here is the aspect of concern and care for the other that is linked to the empathy-remorse-forgiveness cycle in the dialogue between victim and perpetrator. Finally, remorse and its relation to forgiveness are explored. Contextually rich case study material from research on forgiveness illustrates this discussion. PMID- 26671856 TI - Meditations on Psychological Repair: Commentary on Gobodo-Madikizela. PMID- 26671857 TI - Between the Idea and the Reality . . . Falls the Shadow: Commentary on Gobodo Madikizela. PMID- 26671858 TI - How Law, Remorse, and Forgiveness Contribute to Psychological Repair: Commentary on Gobodo-Madikizela. PMID- 26671859 TI - Psychoanalysis in Pursuit of Truth and Reconciliation on a South African Farm: Commentary on Gobodo-Madikizela. PMID- 26671860 TI - What is Psychoanalysis doing in the World of Social Justice? Commentary on Gobodo Madikizela. PMID- 26671861 TI - Introduction: Working with the Analyst's Disappointments, Grief, and Sense of Limitation in the Analytic Process. PMID- 26671862 TI - The Analyst's Disappointment: An Everyday Struggle. PMID- 26671863 TI - Reflections on the Analyst's "Good Enough" Capacity to Bear Disappointment, with Special Attention to Repetition. PMID- 26671864 TI - Disappointment: Something in the Nature of Analysis. PMID- 26671865 TI - The Fog of Disappointment, the Cliffs of Disillusionment, the Abyss of Despair. PMID- 26671867 TI - Journal Watch Review of Behavioral problems after early life stress: Contributions of the hippocampus and amygdala. PMID- 26671868 TI - Journal Watch Review of The neuroscience of mindfulness meditation. PMID- 26671878 TI - Effect of intravenous lidocaine on cough response to endotracheal intubation in propofol-anaesthetized dogs. AB - OBJECTIVE: To determine whether the administration of intravenous (IV) lidocaine before the induction of anaesthesia in premedicated dogs reduces the cough response associated with endotracheal intubation and the propofol dose required. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: A total of 84 client-owned dogs, with American Society of Anesthesiology physical status I and II. METHODS: Dogs received intramuscular (IM) acepromazine 0.02 mg kg(-1) and methadone 0.3 mg kg(-1) and were randomly allocated to one of two groups: saline (group S) and lidocaine (group L). Five minutes before the induction of anaesthesia and 40-50 minutes after premedication, group L received lidocaine (1.5 mg kg(-1) ) and group S received an equal volume of saline solution, each administered slowly IV. Anaesthesia was induced with propofol, initially 2 mg kg( 1) IV over 40 seconds, and then in increments of 0.5 mg kg(-1) every 15 seconds to effect. The same investigator anaesthetized all cases, unaware of group allocation. The following parameters were recorded: pulse rate (PR), mean arterial pressure (MAP, oscillometry), respiratory rate (fR ), sedation score immediately before and 5 minutes after treatment, and total dose of propofol required. Differences in pulse rate, MAP and propofol dose were analysed using the two-sample t-test, coughing incidence was analysed with the chi-square test, and differences in sedation score were analysed with the Mann-Whitney test. RESULTS: After treatment, the incidence of coughing at endotracheal intubation was significantly reduced in group L compared with group S (21% versus 45%; p = 0.022). There was no significant difference between the groups with regard to propofol dose required for endotracheal intubation (p = 0.122), PR (p = 0.611), MAP (p = 0.508) or sedation score (p = 0.051). CONCLUSIONS AND CLINICAL RELEVANCE: IV lidocaine can decrease the incidence of cough during endotracheal intubation in dogs premedicated with acepromazine and methadone, but does not appear to have a sparing effect on the dose of propofol required for endotracheal intubation. Use of IV lidocaine, prior to induction of anaesthesia with propofol may be beneficial in dogs where coughing at intubation would be detrimental. PMID- 26671879 TI - Biochemical and genetic toxicity of the ionic liquid 1-octyl-3-methylimidazolium chloride on earthworms (Eisenia fetida). AB - Ionic liquids also known as "green solvents," are used in many fields. However, the dispersion of ionic liquids in soil systems is likely to cause damage to soil organisms. The objective of the present study was to investigate the toxicity of 1-octyl-3-methylimidazolium chloride ([C8 mim]Cl) on earthworms (Eisenia fetida). For this purpose, earthworms were exposed to different concentrations of [C8 mim]Cl (0 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg artificial soil) and sampled at 7 d, 14 d, 21 d, and 28 d. The results indicated that [C8 mim]Cl could cause an accumulation of reactive oxygen species (ROS) in earthworms, even at the lowest concentration (5 mg/kg). Compared with the controls, during the [C8 mim]Cl exposure period, the activities of superoxide dismutase (SOD) and catalase (CAT) decreased and then increased, whereas the activities of peroxidase (POD) and glutathione S-transferase (GST) increased. These changes in the activities of antioxidant enzymes and GST indicated that [C8 mim]Cl could induce oxidative damage in earthworms. The malondialdehyde content was increased by high levels of [C8 mim]Cl at 14 d and 28 d, indicating that [C8 mim]Cl could lead to lipid peroxidation in earthworms. In addition, the degree of DNA damage significantly increased with increasing [C8 mim]Cl concentrations and exposure time. The present study shows that [C8 mim]Cl caused biochemical and genetic toxicity in earthworms. PMID- 26671880 TI - Mussel-Inspired Polymer Carpets: Direct Photografting of Polymer Brushes on Polydopamine Nanosheets for Controlled Cell Adhesion. AB - 2D mussel-inspired polydopamine (PDA) nanosheets are prepared and exploited as a functional surface for grafting various polymer brushes. The PDA nanosheet and its polymer-brush derivatives show lateral integrity and are robust; therefore, they can be detached from their substrates. Cell-adhesion tests show that the PDA nanosheet promotes cell growth and attachment, while a PDA-based poly(3 sulfopropyl methacrylate) carpet exhibits nonfouling behavior. PMID- 26671881 TI - Release and cellular origin of extracellular vesicles during circulation of whole blood over adsorbent polymers for lipid apheresis. AB - Whole blood lipid apheresis is clinically applied in patients with familial hypercholesterolemia to reduce low density lipoprotein and other apolipoprotein B 100 containing lipoproteins. Here, the hemocompatibility of two polyacrylate coated polyacrylamide-based polymers for lipid apheresis by evaluating the adhesion of blood cells to the adsorbent polymers, their respective activation, as well as the release of microvesicles during circulation of whole blood over the polymers was studied. Characterization of the adsorbents by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy revealed differences with respect to their surface morphology and their surface chemical composition. Despite these differences, equivalent amounts of leukocytes and platelets adhered to both polymers during circulation of whole blood over the adsorbent columns. The release of phosphatidylserine-exposing microvesicles, in contrast, increased significantly with increasing surface roughness and with the amount of polyacrylate groups at the adsorbent surface. The majority of microvesicles generated during blood-material contact were platelet-derived, and their release was associated with enhanced thrombin generation. Microvesicles were present in free and in cell-bound form, and 75% of all monocytes, but only 0.2% and 2.3% of red blood cells and platelets, respectively, were associated with microvesicles, pointing to a role of monocytes in the clearance of released microvesicles. Taken together, microvesicles are sensitive indicators for biomaterial-induced activation of blood cells in apheresis. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 636-646, 2017. PMID- 26671882 TI - Bombing Syria without protecting civilians won't counter extremism or reduce refugees. PMID- 26671883 TI - Aortic Valve Stenosis and Left Main Coronary Disease: Hybrid Approach. AB - We describe a technique of combined transcatheter aortic valve replacement (TAVR), off-pump single coronary artery bypass, and percutaneous coronary intervention (PCI) in a high-risk patient presenting with unstable angina and severe heart failure. This patient had documented moderate to severe aortic stenosis, left ventricular dysfunction, and a heavily calcified ascending aorta. A robotic-assisted left internal thoracic artery harvesting was aborted owing to inability to tolerate single-lung ventilation. A median sternotomy was done, then successful off-pump single-vessel bypass, PCI, and TAVR were achieved. The patient recovered and was discharged from hospital in stable condition. PMID- 26671884 TI - Comparison of Two Methods to Compute Respiratory Volumes Using Optoelectronic Plethysmography. AB - Plethysmography is an indispensable component of clinical lung function testing. However, lung volume measurement in the supine position using an optoelectronic system requires the placement of reflective markers on the anterior and lateral torso surface. The conventional method computes breath-by-breath changes in the volume between the markers and the bed, which serves as the reference plane. In contrast, the surface method consists of measuring the volume delineated by the surface area of the marker network at the onset and end of inspiration. We compared these 2 methods to spirometry during spontaneous breathing in 11 healthy volunteers and in 14 patients receiving routine visits for neuromuscular disease. Bland-Altman plots showed that agreement with spirometry was better for the surface method that the conventional method. Our results open up prospects for integrating these methods in the development of new devices. PMID- 26671886 TI - Retinal Changes in Uncomplicated and Severe Plasmodium knowlesi Malaria. AB - BACKGROUND: Plasmodium knowlesi causes severe malaria, but its pathogenesis is poorly understood. Retinal changes provide insights into falciparum malaria pathogenesis but have not been studied in knowlesi malaria. METHODS: An observational study was conducted in Malaysian adults hospitalized with severe (n = 20) and nonsevere (n = 24) knowlesi malaria using indirect ophthalmoscopy (n = 44) and fundus photography (n = 29). RESULTS: The patients' median age was 44 years (range, 18-74 years). No coma or deaths occurred. Photography detected retinal changes in 11 of 12 patients (92%) with severe and 14 of 17 (82%) with nonsevere knowlesi malaria. Nonspecific retinal whitening occurred in 3 (35%) and 5 (29%) patients with severe and nonsevere disease, respectively; hemorrhages in 2 (17%) and 3 (18%); loss of retinal pigment epithelium in 1 (8%) and 4 (24%); and drusen in 9 (71%) and 12 (75%). All changes were mild, with no significant differences between severe and nonsevere disease. Patients with retinal hemorrhages had lower platelet counts than those without (median, 22 vs 43 * 10(9)/L; P= .04). CONCLUSIONS: The paucity of specific retinal findings associated with disease severity in knowlesi malaria contrasts with the retinopathy of severe adult falciparum malaria with and without coma, suggesting that falciparum-like microvascular sequestration in the brain is not a major component in severe knowlesi malaria pathogenesis. PMID- 26671885 TI - Threading the Needle: Small-Molecule Targeting of a Xenobiotic Receptor to Ablate Escherichia coli Polysaccharide Capsule Expression Without Altering Antibiotic Resistance. AB - BACKGROUND: Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract and invasive infections worldwide, is rapidly acquiring multidrug resistance, hastening the need for selective new anti-infective agents. Here we demonstrate the molecular target of DU011, our previously discovered potent, nontoxic, small-molecule inhibitor of UPEC polysaccharide capsule biogenesis and virulence. METHODS: Real-time polymerase chain reaction analysis and a target overexpression drug-suppressor screen were used to localize the putative inhibitor target. A thermal shift assay quantified interactions between the target protein and the inhibitor, and a novel DNase protection assay measured chemical inhibition of protein-DNA interactions. Virulence of a regulatory target mutant was assessed in a murine sepsis model. RESULTS: MprA, a MarR family transcriptional repressor, was identified as the putative target of the DU011 inhibitor. Thermal shift measurements indicated the formation of a stable DU011 MprA complex, and DU011 abrogated MprA binding to its DNA promoter site. Knockout of mprA had effects similar to that of DU011 treatment of wild-type bacteria: a loss of encapsulation and complete attenuation in a murine sepsis model, without any negative change in antibiotic resistance. CONCLUSIONS: MprA regulates UPEC polysaccharide encapsulation, is essential for UPEC virulence, and can be targeted without inducing antibiotic resistance. PMID- 26671887 TI - SIV/SHIV Infection Triggers Vascular Inflammation, Diminished Expression of Kruppel-like Factor 2 and Endothelial Dysfunction. AB - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with increased risk of thromboembolic and cardiovascular comorbid conditions. Although systemic inflammation is linked to cardiovascular risk, direct evidence of vascular inflammation and endothelial dysfunction is lacking. METHODS: We examined by immunofluorescence microscopy thoracic aortas from 16 simian immunodeficiency virus (SIV)- or simian-human immunodeficiency virus (SHIV) infected and 16 uninfected rhesus macaques. RESULTS: Focal endothelial proliferation and subendothelial inflammatory cells were found in sections of all infected animals, compared with minimal changes in sections from the 16 uninfected controls. In the infected animals, we detected increased endothelial levels of bacterial 16s ribosomal DNA as well as increased subendothelial accumulation of CD68(+) monocytes/macrophages (P< .001) and CD8(+) T lymphocytes (P< .001). Endothelial dysfunction was manifested by decreased levels of endothelial nitric oxide synthase (P< .005) and Kruppel-like factor 2 (KLF2) (P< .005). KLF2 expression was decreased in primary human aortic endothelial cells exposed to bacterial lipopolysaccharide or to oxidized low-density lipoprotein in vitro, and this could be prevented by simvastatin. CONCLUSIONS: SIV and SHIV infection lead to endothelial inflammation, dysfunction, and decreased KLF2 expression reflecting early atherosclerotic changes. Translocated bacterial components and lipid oxidation products may induce endothelial dysfunction in HIV infection that could be prevented by statin treatment. PMID- 26671888 TI - Impact of Antibiotic Use on the Evolution of Enterococcus faecium. PMID- 26671889 TI - Placental Infection With Ureaplasma species Is Associated With Histologic Chorioamnionitis and Adverse Outcomes in Moderately Preterm and Late-Preterm Infants. AB - OBJECTIVE: The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, "moderate/late preterm") infants, the largest cohort of preterm infants. METHODS: Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. RESULTS: We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). CONCLUSIONS: These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists. PMID- 26671891 TI - Fate of new cancer drug is uncertain in Netherlands, as institute deems it too costly. PMID- 26671890 TI - Gastrointestinal Tract Colonization Dynamics by Different Enterococcus faecium Clades. AB - Colonization of the gastrointestinal tract (GIT) generally precedes infection with antibiotic-resistant Enterococcus faecium We used a mouse GIT colonization model to test differences in the colonization levels by strains from different E. faecium lineages: clade B, part of the healthy human microbiota; subclade A1, associated with infections; and subclade A2, primarily associated with animals. After mono-inoculation, there was no significant difference in colonization (measured as the geometric mean number of colony-forming units per gram) by the E. faecium clades at any time point (P > .05). However, in competition assays, with 6 of the 7 pairs, clade B strains outcompeted clade A strains in their ability to persist in the GIT; this difference was significant in some pairs by day 2 and in all pairs by day 14 (P < .0008-.0283). This observation may explain the predominance of clade B in the community and why antibiotic-resistant hospital-associated E. faecium are often replaced by clade B strains once patients leave the hospital. PMID- 26671892 TI - Alabama Parenting Questionnaire-9: Longitudinal Measurement Invariance Across Parents and Youth During the Transition to High School. AB - The Alabama Parenting Questionnaire nine-item short form (APQ-9) is an often used assessment of parenting in research and applied settings. It uses parent and youth ratings for three scales: Positive Parenting, Inconsistent Discipline, and Poor Supervision. The purpose of this study is to examine the longitudinal invariance of the APQ-9 for both parents and youth, and the multigroup invariance between parents and youth during the transition from middle school to high school. Parent and youth longitudinal configural, metric, and scalar invariance for the APQ-9 were supported when tested separately. However, the multigroup invariance tests indicated that scalar invariance was not achieved between parent and youth ratings. Essentially, parent and youth mean scores for Positive Parenting, Inconsistent Discipline, and Poor Supervision can be independently compared across the transition from middle school to high school. However, comparing parent and youth scores across the APQ-9 scales may not be meaningful. PMID- 26671893 TI - Validity and Representative Data of the MRCI With Legally Involved Juveniles. AB - Recognized for nearly four decades, most juvenile suspects waive their Miranda rights and almost immediately provide self-incriminating evidence. Miranda specific measures were eventually developed to understand their capacities and limitations. With extensive revisions, the Miranda Rights Comprehension Instruments (MRCI) were normed and validated. Beyond reliability, the current study addresses the convergent and discriminant validity of the MRCI. In response to Frumkin and Sellbom's criticism of the MRCI's norms, the current research provides representative data on 245 legally involved juveniles with percentiles to facilitate the interpretation of MRCI data. The current investigation is also the first MRCI study to link directly Miranda comprehension (i.e., the knowing prong) to Miranda reasoning (i.e., the intelligent prong) of waiver decisions. PMID- 26671894 TI - Muscle Activation and Performance During Trunk Strength Testing in High-Level Female and Male Football Players. AB - For performance and injury prevention in sport, core strength and endurance are focused prerequisites. Therefore we evaluated characteristics of trunk muscle activation and performance during strength-endurance related trunk field tests. Strength-endurance ability, as total time to failure, and activation of trunk muscles was measured in 39 football players of the highest German female football league (Bundesliga) (N = 18, age: 20.7 y [SD 4.4]) and the highest national male under-19 league (N = 21, age: 17.9 y [0.7]) in prone plank, side plank, and dorsal position. Maximal isometric force was assessed during trunk extension and flexion, rotation, and lateral flexion to normalize EMG and to compare with the results of strength-endurance tests. For all positions of endurance strength tests, a continuous increase in normalized EMG activation was observed (P < .001). Muscle activation of the rectus abdominis and external oblique in prone plank position exceeded the maximal voluntary isometric contraction activation, with a significantly higher activation in females (P = .02). We conclude, that in the applied strength-endurance testing, the activation of trunk muscles was high, especially in females. As high trunk muscle activation can infer fatigue, limb strength can limit performance in prone and side plank position, particularly during high trunk muscle activation. PMID- 26671896 TI - Motives and Barriers to Physical Activity Among Older Adults of Different Socioeconomic Status. AB - This study explored motives and barriers to physical activity (PA) among older adults of differing socioeconomic status (SES) utilizing a self-determination theory and self-efficacy theory framework. Focus groups (n = 4) were conducted with older adults (n = 28) from two SES groups, using thematic analysis to identify motives and barriers. Integrated and identified regulations and, to a lesser extent, intrinsic motives, were evident across SES groups. Verbal persuasion and affective and physiological states emerged as prominent efficacy sources regardless of SES. More barriers were reported by the low SES group, with health conditions, neighborhood safety, and PA guidelines knowledge emerging as most salient. Time emerged as a prominent barrier for the high SES group. Integrated and identified regulations should be fostered in future interventions and policy regardless of SES. Barriers to PA varied across SES groups; thus future interventions and policy should account for such differences. PMID- 26671897 TI - Choosing Wisely: setbacks and progress. PMID- 26671895 TI - 60 YEARS OF POMC: POMC: an evolutionary perspective. AB - Proopiomelanocortin (POMC) is a complex precursor that comprises several peptidic hormones, including melanocyte-stimulating hormones (MSHs), adrenocorticotropic hormone (ACTH), and beta-endorphin. POMC belongs to the opioid/orphanin gene family, whose precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). This gene family diversified during early tetraploidizations of the vertebrate genome to generate four different precursors: proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) as well as POMC, although both PNOC and POMC seem to have arisen due to a local duplication event. POMC underwent complex evolutionary processes, including internal tandem duplications and putative coevolutionary events. Controversial and conflicting hypotheses have emerged concerning the sequenced genomes. In this article, we summarize the different evolutionary hypotheses proposed for POMC evolution. PMID- 26671898 TI - Assessments of Stress of Conscience, Perceptions of Conscience, Burnout, and Social Support Before and After Implementation of a Participatory Action-Research Based Intervention. AB - Interventions aiming to constructively address stress of conscience are rare. The aim of the study was to compare assessments of stress of conscience, perceptions of conscience, burnout, and social support among health care personnel (HCP) working in municipal residential care of older adults, before and after participation in a participatory action research (PAR) intervention aiming to learn to constructively deal with troubled conscience. Questionnaire data were collected at baseline and at follow-up (1-year interval; n = 29). Descriptive statistics and nonparametric statistical tests were used to make comparisons between baseline and follow-up. HCP gave significantly higher scores to the question, "Are your work achievements appreciated by your immediate superior?" at follow-up compared with baseline. No significant differences in levels of stress of conscience and burnout at follow-up were found. The results suggested that a PAR intervention aiming to learn HCP to deal with their troubled conscience in difficult situations could be partially successful. PMID- 26671899 TI - Older Women, Exercise to Music, and Yoga: Senses of Pleasure? AB - This paper examines the lived experience of older women participants in (a) a low impact exercise to music (ETM) class and (b) a yoga class to uncover what is important for them in taking part in these classes. Researcher S is the instructor of the ETM group and draws upon individual and focus group interviews and participant observation. Researcher B is a member of the yoga class where she interviewed the women and undertook participant observations. Both authors are a similar age to the older women interviewees. Through a phenomenological interpretative approach, the paper examines the women's perceptions of their exercise class and yoga experiences, highlighting pleasurable experiences and features that contribute to this enjoyment. The paper considers relationships between pleasure, wellbeing, the senses, physical activity, and aging, drawing upon a variety of analyses. It pays attention to the contextual features of the ETM and yoga classes in making available and accessible pleasurable physical activity experiences for the women and draws, in part, on 'typologies' of pleasure to frame the debate around older women, physical activity, and senses of pleasure. Our research highlights the considerable wellbeing affects for women when physical activity provision takes account of context (the spatial, cultural, social, and sentient). PMID- 26671900 TI - Olfactory Neuroblastoma: Fate of the Neck--A Long-term Multicenter Retrospective Study. AB - OBJECTIVE: Olfactory neuroblastoma and the management of neck disease has posed considerable challenges to the treating physician. The aims of the study were to determine the incidence and factors influencing neck disease and to identify at risk patients with cervical node-negative disease at presentation. STUDY DESIGN: Multicenter case series with retrospective chart review. SETTING AND SUBJECTS: In sum, 113 patients with a histopathologic diagnosis of olfactory neuroblastoma across 6 tertiary hospitals in Australia and the United States. METHODS: Treatment modalities for the primary site and neck included surgery, radiotherapy, and combined therapy. Treatment outcomes were measured in relation to date of primary treatment, and long-term follow-up was recorded. Disease-free survival was calculated as time for patients to develop delayed neck disease following primary treatment. RESULTS: A total of 113 patients (46 females, 49.7 +/- 13.2 years) were identified with a median follow-up of 41.5 months (interquartile range, 58.2); 7.1% of patients presented with primary neck disease, while 8.8% of patients presented with delayed neck disease. Neck disease was present in patients with Hyams grade II (22.2%), III (55.6%), and IV (22.2%) lesions (chi(2) = 5.66, P = .13). Histologic grade was higher in patients with primary neck disease (chi(2) = 16.22, P = .001). Positive surgical margins were associated with a higher risk of delayed neck disease as compared with clear surgical margin (17.9% vs 5%, P = .034). CONCLUSION: Neck metastasis is an important clinical consideration for olfactory neuroblastoma at presentation and in surveillance. Primary treatment of the neck could be considered in select patients. Long-term surveillance of the neck and primary site is essential. PMID- 26671901 TI - AHI Outcomes Are Superior after Upper Airway Reconstructive Surgery in Adult CPAP Failure Patients. AB - OBJECTIVE: This study aims to evaluate Apnea-Hypopnea Index (AHI) outcomes of upper airway adult obstructive sleep apnea (OSA) reconstructive surgery, as compared with outcomes of suboptimal continuous positive airway pressure (CPAP) therapy, in response to reviews claiming unreliable surgical AHI reduction. STUDY DESIGN: Prospective cohort study. SETTING: Single-surgeon series at medical centers within Wollongong, Australia. SUBJECTS AND METHODS: Adult patients with OSA who were partial device users or who refused CPAP were considered candidates for upper airway surgery (N = 48). Subjects underwent physical examination and polysomnography before and after surgery. Three groups were delineated on the nature of their suboptimal CPAP therapy: group 1, partially using CPAP or refusing long-term CPAP despite adherence (with available download data); group 2, unable or refusing to use CPAP with 2 sleep studies over time; group 3, unable or refusing to use CPAP with 1 sleep study over time. Collected data included demographics and AHI outcomes. RESULTS: Average AHI across all 3 groups with suboptimal CPAP therapy before surgery was 30.24 +/- 17.17 events per hour sleep, as compared with the average postoperative AHI of 7.65 +/- 6.59 events per hour sleep. This decrease was shown to be statistically significant with Wilcoxon signed-rank test (P < .0001). CONCLUSIONS: AHI outcomes are superior with surgery in untreated or suboptimally treated adult OSA patients prescribed CPAP. PMID- 26671902 TI - Cochlear Implantation in the Setting of Perioperative Anticoagulation and Antiplatelet Therapy. AB - OBJECTIVE: To describe surgical outcomes and perioperative complications in patients taking antiplatelet and anticoagulation medications while undergoing cochlear implantation. STUDY DESIGN: Case series with chart review. SETTING: Two tertiary otologic referral center. SUBJECTS AND METHODS: Forty-six adult patients (2005-2014) who underwent cochlear implantation while on perioperative antiplatelet and/or anticoagulation therapy without interruption. Outcomes included estimated intraoperative blood loss, perception of increased difficulty secondary to bleeding, and postoperative complications attributable to continuing anticoagulation or antiplatelet therapy. RESULTS: The cases of 46 patients (mean age, 69.5 years; 30.2% female) were analyzed. Of these, 39 patients were taking aspirin, 10 warfarin, and 7 clopidogrel. Aside from 3 (6.5%) patients with postoperative bruising without hematoma and 1 patient (2.2%) who reported self resolving oral cavity blood, no intraoperative or postoperative complications occurred in any patient that could be ascribed to antiplatelet or anticoagulant use. CONCLUSION: These data demonstrate that the risk of perioperative complications from continued antiplatelet or anticoagulation therapy is low. For subjects who are at risk of major complications (eg, deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident) from temporary medication cessation, continuing antiplatelet or anticoagulation therapy through the perioperative period is an appropriate strategy. PMID- 26671903 TI - Adaptation of the Arabic Version of the Tinnitus Handicap Inventory. AB - OBJECTIVE: To translate the Tinnitus Handicap Inventory (THI) into literary Arabic to come up with a unified Arabic version and to determine its validity and reliability in assessing the quality of life of Arabic-speaking patients with tinnitus. STUDY DESIGN: Clinical measurement study. SETTING: Tertiary care center. SUBJECTS AND METHODS: The original English THI was translated into literary Arabic by a forward- and back-translation process according to the published guidelines for cross-cultural adaptation of health-related quality-of life measures and applied to 100 patients with chronic tinnitus. Internal consistency reliability was then assessed by calculating Cronbach's alpha coefficient. Pearson correlation coefficients were also calculated for the different scales and the different baseline characteristics. RESULTS: Results showed high internal consistency and reliability coefficients (total THI: 0.93, functional subscale: 0.86, emotional subscale: 0.86, catastrophic subscale: 0.66) comparable to those of the original English THI. CONCLUSION: The Arabic version of the THI is a valid and reliable tool for the assessment of the impact of tinnitus on the quality of life of Arabic-speaking patients with the complaint of chronic tinnitus. PMID- 26671904 TI - Neck Incision Planning for Total Laryngectomy with Pharyngectomy. AB - OBJECTIVES: To investigate the effect of skin incision location for total laryngectomy with pharyngectomy (TLP) on postoperative outcomes including wound dehiscence and infection rate. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary care center. METHODS: A retrospective analysis was conducted of all patients undergoing TLP with flap closure at Johns Hopkins Medical Institutes between August 2005 and February 2013. The effects of patient characteristics and skin incision technique on postoperative wound dehiscence and infection were analyzed using cross-tabulations and multivariate regression modeling. RESULTS: A total of 49 patients were included in the analysis; 31 received low-neck apron (LNA) incisions with an incorporated tracheostoma, while the remaining 18 had mid-neck apron (MNA) incisions with separate tracheostoma fashioned inferior to their incisions. Of these patients, 17 experienced incisional wound dehiscence (35%), and 18 contracted postoperative infections (37%). Generalized linear regression models demonstrated a significantly increased odds of wound dehiscence for patients with LNA incisions (odds ratio 29.8; 95% CI, 1.4-631.5, P = .029). There were no significant predictive variables for postoperative infection. CONCLUSIONS: These results demonstrate that the use of a separately fashioned tracheostoma with MNA incision is associated with decreased rate of wound dehiscence in patients undergoing TLP. PMID- 26671906 TI - Effects of Pilates Exercise on Salivary Secretory Immunoglobulin A Levels in Older Women. AB - We examined the effects of a Pilates exercise program on the mucosal immune function in older women. The study population comprised 12 older women who were divided into a Pilates group (PG, n = 6) and a control group (CG, n = 6). Saliva samples were obtained from both groups before and after the experimental period for salivary secretory immunoglobulin A level measurement. In addition, acute high-intensity exercises were performed before and after the three-month Pilates exercise program. After three months, salivary flow was significantly higher in the PG than in the CG. After the acute high-intensity exercises were performed following the three-month Pilates exercise program, the salivary flow rate was significantly higher at all time points. The S-IgA secretion rate significantly increased 30 min after acute high-intensity exercise performed following the three-month Pilates exercise program. This study suggests that regular participation in a moderate-intensity Pilates exercise program can increase salivary flow rate and S-IgA secretion in older women. PMID- 26671905 TI - Socioeconomic Factors Affect Outcomes in Well-Differentiated Thyroid Cancer. AB - OBJECTIVES: The effects of socioeconomic status (SES) on the incidence of well differentiated thyroid cancer (WDTC) are well researched. However, the association between SES and outcomes is not delineated. Our objective was to determine if SES affected outcomes of WDTC. STUDY DESIGNS: Retrospective database review. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: The Henry Ford Virtual Data Warehouse Tumor Registry was used to identify cases of WDTC. Socioeconomic data were obtained through the 2010 US Census: median household income, percentage below poverty line, median household size, percentage rent versus own property, and general demographics. Survival was the primary outcome. Disease-specific survival was also calculated. Cox proportional hazards were calculated and a multivariate analysis performed. RESULTS: There were 1317 patients with WDTC. In multivariable analysis, median household income (hazard ratio [HR]: 0.85, 95% confidence interval [95% CI]: 0.79-0.91), household size (HR: 1.49, 95% CI: 1.09-2.14), younger age (HR: 1.97, 95% CI: 1.74-2.23), and female sex (HR: 0.50, 95% CI: 0.37-0.69) were significantly associated with survival. Controlling for stage revealed percentage below poverty line (stage I, HR: 0.51, 95% CI: 1.34-1.78; stage IV, HR: 1.28, 95% CI: 1.04-1.57) and median household income (HR: 0.84, 95% CI: 0.71-0.99) to be significant factors in survival. Median household income was a statistically significant variable for disease-related death (HR: 0.82, 95% CI: 0.69-0.96) CONCLUSIONS: Along with effects on incidence, lower SES correlates with worse survival in WDTC. This suggests that a patient's economic background, with younger age and female sex, influences one's outcomes with regard to both overall and disease-specific death. PMID- 26671907 TI - US research bodies aren't reporting trial results as required, report finds. PMID- 26671908 TI - Physical Activity and Aging Research: A Bibliometric Analysis. AB - Physical activity and aging research has burgeoned in the past few decades. However, despite the increase in scholarly publications, no attempts have been made to summarize the publication landscape and identify work that has had great impact on physical activity and aging research. We conducted a bibliometric analysis and collected publication data from 1980 to February 6, 2015, in the Web of Science Core Collection. Of 9,935 publications, most were published after 2007 and almost 60% were in the category of geriatrics and gerontology or sport sciences. Highly cited publications (n = 45) were mostly authored by researchers from US institutions and were quantitative in nature. Publications that reported on the associations between physical activity and health, or effects of physical activity on health, in older adults made up 60% of the highly cited publications. We expect more scholars from various backgrounds and geographical regions to join the conversation on physical activity and aging. PMID- 26671910 TI - Corrigendum: Popularity, Similarity, and the Network Extraversion Bias. PMID- 26671909 TI - Changing Environments by Changing Individuals: The Emergent Effects of Psychological Intervention. AB - The two studies reported here tested whether a classroom-based psychological intervention that benefited a few African American 7th graders could trigger emergent ecological effects that benefited their entire classrooms. Multilevel analyses were conducted on data that previously documented the benefits of values affirmations on African American students' grades. The density of African American students who received the intervention in each classroom (i.e., treatment density) was used as an independent predictor of grades. Within a classroom, the greater the density of African American students who participated in the intervention exercise, the higher the grades of all classmates on average, regardless of their race or whether they participated in the intervention exercise. Benefits of treatment density were most pronounced among students with a history of poor performance. Results suggest that the benefits of psychological intervention do not end with the individual. Changed individuals can improve their social environments, and such improvements can benefit others regardless of whether they participated in the intervention. These findings have implications for understanding the emergence of ecological consequences from psychological processes. PMID- 26671911 TI - Large Cross-National Differences in Gene * Socioeconomic Status Interaction on Intelligence. AB - A core hypothesis in developmental theory predicts that genetic influences on intelligence and academic achievement are suppressed under conditions of socioeconomic privation and more fully realized under conditions of socioeconomic advantage: a Gene * Childhood Socioeconomic Status (SES) interaction. Tests of this hypothesis have produced apparently inconsistent results. We performed a meta-analysis of tests of Gene * SES interaction on intelligence and academic achievement test scores, allowing for stratification by nation (United States vs. non-United States), and we conducted rigorous tests for publication bias and between-studies heterogeneity. In U.S. studies, we found clear support for moderately sized Gene * SES effects. In studies from Western Europe and Australia, where social policies ensure more uniform access to high-quality education and health care, Gene * SES effects were zero or reversed. PMID- 26671912 TI - Variable brain phenotype primarily affects the brainstem and cerebellum in patients with osteogenesis imperfecta caused by recessive WNT1 mutations. PMID- 26671913 TI - Local genotype influences DNA methylation at two asthma-associated regions, 5q31 and 17q21, in a founder effect population. AB - BACKGROUND: Two asthma-associated regions 17q12-q21 and 5q31.1 harbour genes that show strong effect of genotype on expression levels. DNA methylation has an important role in gene regulation; therefore, we examined DNA methylation at promoters of 12 genes from 5q31 and 17q12-q21 regions. Our goal was to determine whether DNA methylation was associated with predisposition to asthma and whether such a relationship was independent from genetic association. METHODS: Using sodium bisulfite sequencing and pyrosequencing methylation assays, we examined the effect of genotype on DNA methylation in peripheral blood cells from individuals from the Saguenay-Lac-Saint-Jean asthma familial collection and lymphoblastoid cell lines. RESULTS: The local genotype influenced methylation levels of solute carrier family 22 (organic 3 cation/carnitine transporter) member 5 (SLC22A5), zona pellucida binding protein 2 (ZPBP2) and gasdermin A (GSDMA) promoter regions. The genotype had a dominant effect on ZPBP2 and GSDMA methylation with lower methylation levels in individuals that carry the asthma predisposing alleles. Males also had lower methylation at the ZPBP2 promoter than females. We did not observe an effect of asthma status that would be independent of the genotype and the sex effects in the GSDMA, ZPBP2 and SLC22A5 regions; however, GSDMA and ZPBP2 data were suggestive of interaction between asthma and methylation levels in females and SLC22A5 in males. CONCLUSIONS: The local genotype influences methylation levels at SLC22A5 and ZPBP2 promoters independently of the asthma status. Further studies are necessary to confirm the relationship between GSDMA-ZPBP2 and SLC22A5 methylation and asthma in females and males separately. PMID- 26671914 TI - [Dual action of vitamin C versus degradation and supplementation]. AB - The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetology, rheumatology, immunology and dietetics. The latest research with respect to vitamin C proved that it has the ability to dissolve neurotoxic senile plaques. Equally effective in the treatment of Alzheimer's disease is the oxidised form of vitamin C, i.e. dehydroascorbic acid. Vitamin C may be used in a combined vitamin E supplementation to avoid the pro-oxidative effect and reduce the risk of diabetes mellitus type 2 complications. In the review there is a description of the types of vitamin C degradation depending on a specific factor such as pH, temperature, oxygen, enzyme and the impact of diet on the quantity of the supplied vitamin. The literature data confirmed the positive influence of vitamin C as an addition to food. The last part of the article presents the methods of vitamin C protection used in food processing technology and of determining its content in food products. Additionally, the article describes the problems related to vitamin C oxidation processes during food processing and storage. The presented research results indicate that an adequate diet contains a sufficient amount of vitamin C for healthy people. In the case of chronic patients it is better to use supplementation. PMID- 26671915 TI - Association between ins4436A in 11beta-hydroxysteroid dehydrogenase type 1 gene and essential hypertension in Polish population. AB - BACKGROUND: Essential hypertension (EH) is the most common cardiovascular disease worldwide, and it has a strong genetic component. Cortisol homeostasis is an important factor in controlling blood pressure, and the availability of this hormone is regulated by 11betahydroxysteroid dehydrogenase type 1 enzyme (11betaHSD1), which converts cortisone into cortisol. MATERIALS AND METHODS: We investigated the correlation between EH and the single nucleotide polymorphism (SNP) ins4436A located on the hydroxysteroid (11-beta) dehydrogenase 1 gene among the Polish population. The study included a total of 268 patients with confirmed EH and 151 unrelated controls. All studied polymorphisms were detected using the restriction fragment length polymorphism (RFLP) method. RESULTS: The carriage of ins4436A (rs45487298) polymorphism in intron 3 of the HSD11B1 gene was more frequent among patients with EH than among controls (p=0.013). The analysis of association of ins4436A with the risk of EH indicated an odds ratio (OR) of 2.44 (95% confidential interval: 1.24-4.82). Moreover, essential hypertension occurred less frequently in males than in females. Results of multivariate analysis in the study group showed that ins4436A is a strong predictor of diabetes mellitus type 2 and ins4436A may lead to a decrease of the high-density lipoprotein (HDL) cholesterol level. DISCUSSION: The cause of essential hypertension has not been fully established, but genetic factors seem to play a very important role. In our study we found that ins4436A in the HSD11B1 gene was associated with essential hypertension in a Polish population. Nevertheless, the impact of ins4436A in the HSD11B1 gene on the occurrence of essential hypertension requires further investigations. PMID- 26671916 TI - Retinal degeneration following lead exposure - functional aspects. AB - Due to the prevalence of lead (Pb) in the environment, the neurotoxic effects on the human body have become an important clinical problem. Despite that Pb concentration in the environment decreased after banning its use in petrol, it is still a significant issue which can affect child development and vision. This paper focuses on the degeneration of the retina under exposure to lead. We present the most frequent sources of exposure to lead in the environment and the influence on vision, mechanisms leading to the apoptosis of photoreceptor cells, as well as strategies for blocking rod apoptosis. We also present Pb-induced disorders in the calcium metabolism of photoreceptor cells and Ca2+-dependent enzymes. PMID- 26671917 TI - Expression of cyclin A in A549 cell line after treatment with arsenic trioxide. AB - BACKGROUND: Arsenic trioxide (ATO) is an effective drug used in acute promyelocytic leukemia (AML). Many reports suggest that ATO can also be applied as an anticancer agent for solid tumors in the future. The influence of arsenic trioxide on the expression of different cell cycle regulators is poorly recognized. The purpose of the current study is to investigate how arsenic trioxide affects cyclin A expression and localization in the A549 cell line. MATERIALS AND METHODS: Morphological and ultrastructural changes in A549 cells were observed using light and transmission electron microscopes. Cyclin A localization was determined by immunofluorescence. Image-based cytometry was applied to evaluate the effect of arsenic trioxide on apoptosis and the cell cycle. Expression of cyclin A mRNA was quantified by real-time PCR. RESULTS: After treatment with arsenic trioxide, increased numbers of cells with cytoplasmic localization of cyclin A were observed. The doses of 10 and 15 MUM ATO slightly reduced expression of cyclin A mRNA. The apoptotic phenotype of cells was poorly represented, and the Tali imagebased cytometry analysis showed low percentages of apoptotic cells. The A549 population displayed an enriched fraction of cells in G0/G1 phase in the presence of 5MUM ATO, whereas starting from the higher concentrations of the drug, i.e. 10 and 15 MUM ATO, the G2/M fraction was on the increase. DISCUSSION: Low expression of cyclin A in the A549 cell line may constitute a potential factor determining arsenic trioxide resistance. It could be hypothesized that the observed alterations in cyclin A expression/distribution may correlate well with changes in cell cycle regulation in our model, which in turn determines the outcome of the treatment. PMID- 26671918 TI - Prognostic significance of MCM 2 and Ki-67 in neuroblastic tumors in children. AB - INTRODUCTION: Neuroblastic tumors can be characterized by three features: spontaneous regression, maturation and aggressive proliferation. The most common and routinely used method of assessing tumor cell proliferation is to determine the Ki-67 index in the tumor tissue. Despite numerous studies, neuroblastoma biology is not fully understood, which makes treatment results unsatisfactory. MCM 2 is a potential prognostic factor in the neuroblastoma group. MATERIAL/METHODS: The study is based on retrospective analysis of 35 patients treated for neuroblastic tumors in the Department of Pediatric Surgery and Oncology of the Medical University of Lodz, during the period 2001-2011. The material comprised tissues of 16 tumors excised during the operation and 19 biopsy specimens. Immunohistochemical examinations were performed with immunoperoxidase using mouse monoclonal anti-MCM 2 and anti-Ki-67 antibodies. RESULTS: We observed that MCM 2 expression ranged from 2% to 98% and the Ki-67 index ranged from 0 to 95%. There was a statistically significant correlation between expression of MCM 2 and the value of the Ki-67 index and a correlation close to statistical significance between expression of MCM 2 and unfavorable histopathology. There was no statistical relationship between expression of MCM 2 and age over 1 year and N-myc amplification. DISCUSSION: The presented research shows that MCM 2 may have prognostic significance in neuroblastic pediatric tumors and as a potential prognostic factor could be the starting point of new individualized therapy. PMID- 26671919 TI - [Ovarian cancer--from biology to clinic]. AB - Ovarian cancer is the most frequent cause of deaths from among gynecologic malignancies. Due to its asymptomatic development the disease is frequently diagnosed at an advanced, incurable stages. Although ovarian cancers usually respond well to the first line chemotherapy based on platinum compounds and taxanes, majority of patients develop recurrence and chemo-resistance. Despite many years of studies there is still lack of reliable diagnostic markers as well as other diagnostic methods enabling early detection and suitable for screening. Thus, current studies are aimed on finding new biomarkers with diagnostic, prognostic and predictive potential as well as on the search for the new therapeutic targets. Interestingly, an understanding of ovarian cancer etiology has changed fundamentally within recent years. The classical theory, claiming that ovarian cancers originate from ovarian surface epithelial cells, was undermined. Currently, there is a lot of evidence that majority of serous ovarian cancers have its origin in malignant tubal epithelium, while endometrioid and clear cell ovarian cancers develop most likely from endometriosis. These new findings will have an impact on diagnostic approaches as well as on the prevention options for women with genetic predisposition to ovarian cancer. The new knowledge about an origin of different histological types of ovarian cancer may open new pathways in basic research and clinical studies. In this paper we report current knowledge about ovarian cancer risk factors, we also present the arguments for extraovarian origin of the majority of ovarian cancers and stress the mechanisms of action of new drugs for targeted therapies that show most promising results in the current clinical trials. PMID- 26671920 TI - Activity of JAK/STAT and NF-kB in patients with axial spondyloarthritis. AB - BACKGROUND: The etiology of axial spondyloarthritis (axSpA) is not fully elucidated. Research continues in determining the mechanisms responsible for initiation of the disease process, its maintenance and development. OBJECTIVES: The aim of this study was to evaluate the expression of transcription factors STAT (signal transducer and activator of transcription) and NF-kappaB (nuclear factor kappa B) as well as Janus kinase3 (JAK3) in the peripheral blood leukocytes. We also analyzed the connection between the degree of activation of transcription factors and the disease activity. MATERIAL/METHODS: The study involved 46 patients with axSpA and 19 healthy individuals who comprised the control group. The expression of NF-kappaB, STAT1, STAT3, STAT4, STAT5, STAT6, and JAK3 in peripheral blood leukocytes was assessed. To determine the degree of activation of transcription factors STAT-s and NF-kappaB and JAK3 kinase, the immunocytochemistry method was used. For location of the factors, the primary monoclonal anti-NF-kappaB, anti-JAK3 and polyclonal anti-STAT-s antibodies were used (Chemicon International, USA, Abcam, Cambridge, UK), and the set of antibodies Novocastain Super ABC Kit (Novocastra, UK). RESULTS: Expression of STAT1, STAT3, STAT4, STAT5, STAT6, NF-kappaB and JAK3 was statistically higher in the group of patients with axSpA than in the control group. There was a positive correlation with ESR values and expression of STAT4. There was no correlation between STAT, NF-kappaB, and JAK3 expression and ASDAS, BASDAI, and BASFI. Nine patients were treated with TNF-alpha inhibitors. The expression of NF-kappaB and STAT6 was higher in the group treated with TNF-alpha inhibitors, even though disease activity in these patients was shown to be lower than in those not receiving such treatment (ASDAS = 1.34+/-0.51 vs. 3.52+/-0.90, BASDAI = 2.34+/ 1.92 vs. 5.51+/-2.41). CONCLUSIONS: In the group of patients with axSpA compared with the control group, higher expression of the transcription factors STAT and NF-kappaB as well as JAK3 was observed. Due to its crucial roles in inflammation and autoimmunity, STAT4 may have promise as an effective therapeutic target for axSpA. PMID- 26671921 TI - [Immunosuppression - tough ally in torrid time]. AB - Immunosuppression is a condition characterized by weakened or inhibited immune response. It occurred both in humoral and cellular response. This is related to the variable levels of deficiency for each antibody class (IgG, IgM, IgA) and a decrease in the number and function of immune cells, mainly T cells which results in the inhibition of cytokine production, signaling transduction and clonal expansion. Immunosuppressive therapy is used in many fields of medicine, such as transplantology, oncology, autoimmune disorders. Immunosuppression can be induced in several ways, by the surgical resection of the organs of the immune system, physical methods using X-rays or chemical methods using pharmacological agents. The most common way to induce immunosuppression is the administration of immunosuppressive drugs, amongst others: glucocorticoids, cytostatic drugs, immunophilin-binding agents, monoclonal antibodies. Unfortunately, the desired therapeutic effects of immunosuppression may be accompanied by a number of side effects associated with both impaired immunity (susceptibility to infections, including those caused by opportunistic microorganisms), toxic effects on the tissues (nephrotoxicity, neurotoxicity), or with a direct impact on the processes of malignancy. This harmful influence can be limited by the modification of the existing drugs, looking for new ones or developing new methods for the controlled kinetics of releasing the immunosuppressive pharmaceuticals. The personalization of immunosuppressant treatment according to genetic/genomic characteristics of individual patient represents the quite innovative look into the issue of immunosuppression. PMID- 26671923 TI - [Skin diseases associated with hepatitis C virus]. AB - Chronic hepatic diseases caused by HBV or HCV infection not always demonstrate evident clinical symptoms of liver disease. Non-specific extrahepatic symptoms mainly skin leasions are helpful for establishing the proper diagnosis. This review illustrates the pathogenesis, epidemiology and clinical manifestations of HBV and HCV infections with a special attention to skin signs and symptoms which can associate these infections. PMID- 26671922 TI - [Trastuzumab - a monoclonal antibody - and dendrimers in a targeted therapy for breast cancer]. AB - Breast cancer is the most frequently occurring cancer in women. It has been confirmed that approximately 30% of patients have overexpression of human epidermal growth factor 2 (HER2) on the surface of tumor cells. Trastuzumab - a recombinant, humanized monoclonal antibody - is directed against this receptor. Its use in traditional chemotherapy (with anthracyclines or taxanes) causes an increase of therapy efficiency. However, the systemic toxicity of the anticancer drugs is still a serious problem. Therefore, new solutions are sought, especially in the field of selective drug transport to tumor cells. Dendrimers are composed of a core and branches. They are the bestknown group of nanoparticles. A lot of publications have shown that they can be used as carriers of various types of molecules, including anticancer drugs. The branched structure provides effective protection against premature release of the drug into the circulatory system. It gives a chance to reduce the dose while maintaining a therapeutic effect, and to reduce the toxicity of the drug for normal cells. Furthermore, the surface of dendrimers can be modified by a monoclonal antibody to achieve a targeted therapy. For that reason synthesis of conjugates of trastuzumab, dendrimers, and anticancer drugs is so crucial. This paper presents an overview of publications about the use of trastuzumab in in vitro, in vivo and clinical studies, as well as the latest developments of biology and chemistry, whose goal is to create the perfect, targeted carrier. PMID- 26671924 TI - [Neurofibromin - protein structure and cellular functions in the context of neurofibromatosis type I pathogenesis]. AB - Neurofibromatosis type I (NF1) is multisystemic disease characterized by pigmentary skin changes, increased susceptibility to tumor formation, neurological deficits and skeletal defects. The disease is a monogenic, autosomal dominant disorder, caused by the presence of mutations in the NF1 gene encoding neurofibromin - a multifunctional regulatory protein. The basic function of neurofibromin protein is modulation of the RAS protein activity necessary for regulation of cell proliferation and differentiation by the RAS/MAPK and RAS/PI3K/AKT signal transduction pathways. In addition, neurofibromin is a regulator of adenylate cyclase activity and therefore may interfere with signaling by the cAMP/protein kinase A pathway that regulates cell cycle progression or learning and memory formation processes. Neurofibromin also interacts with many other proteins that are engaged in intracellular transport (tubulin, kinesin), actin cytoskeleton rearrangements (LIMK2, Rho and Rac) or morphogenesis of neural cells (syndecans, CRMP proteins). The activity of neurofibromin is strictly regulated by the expression of different NF1 mRNA isoforms depending on tissue type or period in organism development, the protein localization, posttranslational modifications (phosphorylation, ubiquitination) or interactions with other proteins (e.g. 14-3-3). The fact that neurofibromin is engaged in many cellular processes has significant consequences when the proper protein functioning is impaired due to decreased protein level or activity. It affects the normal cell function and results in disturbances of organism development that lead to the occurrence of clinical signs specific for NF1. In the article, the basic neurofibromin functions are presented in the context of the molecular pathogenesis of NF1. PMID- 26671925 TI - Prevalence of human papillomavirus and herpes simplex virus in amniotic fluid from pregnant women of Eastern Poland. AB - BACKGROUND: The exact route of human papillomavirus (HPV) and herpes simplex virus (HSV) transmission from a pregnant woman to her fetus has not been clearly established thus far. The data of many studies raise the possibility of intrauterine infection. In order to clarify our knowledge about virus vertical transmission in pregnant women, viral prevalence in amniotic fluid cannot. To the best of our knowledge, this is the first study on HPV DNA and HSV DNA detection in amniotic fluid in Poland. MATERIAL AND METHODS: The study covered 138 samples of amniotic fluid from patients undergoing invasive prenatal diagnostic procedures (for medical indications) during the second trimester of gestation. The aim of the study was to assess the prevalence of HPV and HSV in the amniotic fluid samples obtained from asymptomatic women with intact amniotic membranes. To identify viral DNA of HPV and HSV in collected material, polymerase chain reaction (PCR) was performed. RESULTS: We did not find HPV or HSV DNA in any of the examined specimens of amniotic fluid. CONCLUSION: Our investigation did not confirm the prenatal transmission of HPV and HSV to the amniotic fluid. PMID- 26671926 TI - [Programmed necrosis and necroptosis - molecular mechanisms]. AB - Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor alpha, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis. PMID- 26671927 TI - [Comorbidities as risk factors of chronic kidney disease in HIV-infected persons]. AB - Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons. PMID- 26671929 TI - Corrigendum. PMID- 26671928 TI - [TET proteins and epigenetic modifications in cancers]. AB - Epigenetic modifications, including DNA methylation and histone modifications, are involved in regulation of gene expression, and alterations in these modifications are implicated in cancer onset and progression. The specific pattern of DNA methylation depends on the balance between methylation and demethylation processes. Recent studies have shown that TET proteins play a key role in DNA demethylation. TET proteins (TET1, TET2, TET3) are iron(II) and alpha ketoglutarate dependent dioxygenases, and their enzymatic activity involves hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine and further to 5 formylcytosine and 5-carboxylcytosine. These modified cytosines are removed by enzymes involved in DNA repair. However, the role of TETs in gene expression regulation is not limited to their catalytic activity. TETs can interact with proteins of complexes involved in the modification of histones (i.e. EZH2, OGT, Sin3a or HCF1) and by affecting their activity and, chromatin binding ability, they can cause changes in patterns of histone methylation, acetylation and O GlcNAcylation. There is growing evidence that decreased expression of TET proteins and mutation in TET genes are associated with cancer onset and progression. PMID- 26671930 TI - Climate patriots? Concern over climate change and other environmental issues in Australia. AB - Echoing the anti-pollution and resource conservation campaigns in the United States in the early-to-mid-twentieth century, some scholars advocate mobilising support for environmental issues by harnessing the notion of environmental patriotism. Taking action to reduce the impact of global warming has also been cast as a patriotic cause. Drawing upon quantitative data from a recent national survey, we examine the link between patriotism and environmental attitudes in Australia, focussing upon climate change. We find that patriotism has a largely neutral association with concern over environmental issues, with the exception of climate change and, to a lesser extent, wildlife preservation. Expressing concern over climate change appears to be unpatriotic for some Australians. Even after controlling for political party identification and other important correlates of environmental issue concerns, patriots are less likely than others to prioritise climate change as their most urgent environmental issue and less likely to believe that climate change is actually occurring. PMID- 26671931 TI - Ablation of Atrial Fibrillation: How Can Less Be More? PMID- 26671932 TI - Epicardial Substrate Ablation in Brugada Syndrome: Time for a Randomized Trial! PMID- 26671933 TI - Quinidine in Brugada Syndrome: Still a Long Way to Go.... PMID- 26671934 TI - Left Ventricular Involvement in ARVD/C: Is It Time to Readjust Our Views? PMID- 26671935 TI - Matter of Fat: Are Lipids Antiarrhythmic? PMID- 26671936 TI - Unusual Incessant Ventricular Tachycardia: What Is the Underlying Cause and the Possible Mechanism? PMID- 26671937 TI - Reciprocating Reentry. PMID- 26671938 TI - Integration of High-Resolution Optical Mapping and 3-Dimensional Micro-Computed Tomographic Imaging to Resolve the Structural Basis of Atrial Conduction in the Human Heart. PMID- 26671939 TI - First-in-Man Coronary Sinus Lead Stabilization Using a Bioresorbable Vascular Scaffold System. PMID- 26671940 TI - Letter by Sun et al Regarding Article, "Electrogram Analysis and Pacing Are Complimentary for Recognition of Abnormal Conduction and Far-Field Potentials During Substrate Mapping of Infarct-Related Ventricular Tachycardia". PMID- 26671941 TI - Response to Letter Regarding Article, "Electrogram Analysis and Pacing Are Complimentary for Recognition of Abnormal Conduction and Far-Field Potentials During Substrate Mapping of Infarct-Related Ventricular Tachycardia". PMID- 26671942 TI - Recent advancement in the challenges to connectomics. AB - Advancement of microscopic technologies established significant progress in our understanding of the brain. In the recent effort to elucidate the complete wiring map of the brain circuitry termed 'connectome', the different modalities of imaging technology, including those of light and electron microscopy, have started providing essential contribution in multiple organisms. The contribution would be impossible without the recent innovation in both acquisition and analyses of the big connectomic data. The current data demonstrated complicated networks with unidirectional and reciprocal connections of the cerebral circuits at the macroscopic and light microscopic ('mesoscopic') levels, and the unimaginable complexity of synaptic connections between axons and dendrites at the electron microscopic ('microscopic') level. At the same time, the data highlighted the necessity to make substantial advancement in methodology of the connectomic studies, including efficient handling and automated analyses of the acquired dataset. Further understanding about structural and functional connectome seems to be facilitated by combinations of the different imaging modalities. Such multidisciplinary approaches will give us the clues to address whether the complete connectome can elucidate fundamental mechanisms processing the basic and higher functions of human brains. PMID- 26671943 TI - Sample preparation of biological macromolecular assemblies for the determination of high-resolution structures by cryo-electron microscopy. AB - Single particle cryo-EM has recently developed into a powerful tool to determine the 3D structure of macromolecular complexes at near-atomic resolution, which allows structural biologists to build atomic models of proteins. All technical aspects of cryo-EM technology have been considerably improved over the last two decades, including electron microscopic hardware, image processing software and the ever growing speed of computers. This leads to a more widespread use of the technique, and it can be anticipated that further automation of electron microscopes and image processing tools will soon fully shift the focus away from the technological aspects, onto biological questions that can be answered. In single particle cryo-EM, no crystals of a macromolecule are required. In contrast to X-ray crystallography, this significantly facilitates structure determination by cryo-EM. Nevertheless, a relatively high level of biochemical control is still essential to obtain high-resolution structures by cryo-EM, and it can be anticipated that the success of the cryo-EM technology goes hand in hand with further developments of sample purification and preparation techniques. This will allow routine high-resolution structure determination of the many macromolecular complexes of the cell that until now represent evasive targets for X-ray crystallographers. Here we discuss the various biochemical tools that are currently available and the existing sample purification and preparation techniques for cryo-EM grid preparation that are needed to obtain high-resolution images for structure determination. PMID- 26671944 TI - Automated data collection in single particle electron microscopy. AB - Automated data collection is an integral part of modern workflows in single particle electron microscopy (EM) research. This review surveys the software packages available for automated single particle EM data collection. The degree of automation at each stage of data collection is evaluated, and the capabilities of the software packages are described. Finally, future trends in automation are discussed. PMID- 26671946 TI - Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study. AB - OBJECTIVES: To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). DESIGN AND SETTING, AND PATIENTS: DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases. MAIN OUTCOME MEASURES: All-cause mortality and MACE. RESULTS: After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD. CONCLUSIONS AND RELEVANCE: Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD. PMID- 26671947 TI - Clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in Iran: the Iranian Project for Assessment of Coronary Events 2 (IPACE2). AB - OBJECTIVES: To assess contemporary data on characteristics, management and 1-year postdischarge outcomes in Iranian patients hospitalised with acute coronary syndrome (ACS). SETTING: 11 tertiary care hospitals in 5 major cities in the Islamic Republic of Iran. PARTICIPANTS: Patients aged >= 20 and <= 80 years discharged alive with confirmed diagnosis of ACS including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and high-risk unstable angina (HR-UA). PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were followed up regarding the use of medications and the end points of the study at 1 month and 1 year after discharge. The primary end point of the study was 1-year postdischarge major adverse cardiac and cerebrovascular events (MACCEs), defined as mortality (cardiac and non-cardiac), ACS and cerebrovascular attack (stroke and/or transient ischaemic attack). The secondary end points were hospital admission because of congestive heart failure, revascularisation by coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), and major and minor bleeds. RESULTS: A total of 1799 patients (25.7% STEMI and 74.3% HR-UA/NSTEMI) discharged alive with confirmed diagnosis of ACS were included in the final analysis. During hospitalisation, the majority of the patients received aspirin (98.6%), clopidogrel (91.8%), anticoagulants (93.4%), statins (94.3%) and beta blockers (89.3%). Reperfusion therapy was performed in 62.6% of patients with STEMI (46.3% thrombolytic therapy and 17.3% primary PCI). The mean door-to balloon and door-to-needle times were 82.9 and 45.6 min, respectively. In our study, 64.7% and 79.5% of the patients in HR-UA/NSTEMI and STEMI groups, respectively, underwent coronary angiography. During the 12 months after discharge, MACCEs occurred in 15.0% of all patients. CONCLUSIONS: Our study showed that the composition of Iranian patients with ACS regarding the type of ACS is similar to that in developed European countries and is unlike that in developing countries of the Middle East and Africa. We found that our patients with ACS are treated with high levels of adherence to guideline-recommended in hospital medications. PMID- 26671948 TI - Survival analysis of time to uptake of modern contraceptives among sexually active women of reproductive age in Nigeria. AB - OBJECTIVE: To assess the timing of modern contraceptive uptake among married and never-married women in Nigeria. DESIGN: A retrospective cross-sectional study. DATA AND METHOD: We used nationally representative 2013 Demographic and Health Survey data in Nigeria. Modern contraceptive uptake time was measured as the period between first sexual intercourse and first use of a modern contraceptive. Non-users of modern contraceptives were censored on the date of the survey. Kaplan-Meier survival curves were used to determine the rate of uptake. A Cox proportional-hazards model was used to determine variables influencing the uptake at 5% significance level. PARTICIPANTS: A total of 33,223 sexually active women of reproductive age. OUTCOME MEASURE: Time of uptake of a modern contraceptive after first sexual intercourse. RESULTS: The median modern contraceptive uptake time was 4 years in never-married and 14 years among ever-married women. Significant differences in modern contraceptive uptake existed in respondents' age, location, education and wealth status. Never-married women were about three times more likely to use a modern contraceptive than ever-married women (aHR=3.24 (95% CI 2.82 to 3.65)). Women with higher education were six times more likely to use a modern contraceptive than those without education (aHR=6.18 (95% CI 5.15 to 7.42)). CONCLUSIONS: The rate of modern contraceptive uptake is low, and timing of contraceptive uptake during or after first sexual intercourse differed according to marital status. Age and number of children ever born influenced modern contraceptive uptake among the never-married women, but religion and place of residence were associated with the probability of modern contraceptive uptake among ever-married women. PMID- 26671950 TI - Unintentional, non-fatal drowning of children: US trends and racial/ethnic disparities. AB - OBJECTIVE: The current study aimed to better understand trends and risk factors associated with non-fatal drowning of infants and children in the USA using two large, national databases. METHODS: A secondary data analysis was conducted using the National Inpatient Sample and the Nationwide Emergency Department Sample databases. The analytic sample (n=19,403) included children <21 years of age who had a diagnosis code for near-drowning/non-fatal drowning. Descriptive, chi(2) and analysis of variance techniques were applied, and incidence rates were calculated per 100,000 population. RESULTS: Non-fatal drowning incidence has remained relatively stable from 2006 to 2011. In general, the highest rates of non-fatal drowning occurred in swimming pools and in children from racial/ethnic minorities. However, when compared with non-Hispanic Caucasian children, children from racial/ethnic minorities were more likely to drown in natural waterways than in swimming pools. Despite the overall lower rate of non-fatal drowning among non Hispanic Caucasian children, the highest rate of all non-fatal drowning was for non-Hispanic Caucasian children aged 0-4 years in swimming pools. Children who were admitted to inpatient facilities were younger, male and came from families with lower incomes. CONCLUSIONS: Data from two large US national databases show lack of progress in preventing and reducing non-fatal drowning admissions from 2006 to 2011. Discrepancies are seen in the location of drowning events and demographic characteristics. New policies and interventions are needed, and tailoring approaches by age and race/ethnicity may improve their effectiveness. PMID- 26671949 TI - Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches. AB - OBJECTIVES: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature. SETTING: 9 British cohorts belonging to the HALCyon collaboration. PARTICIPANTS: Individual participant data on N=26,692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50-79 years were available for inclusion in observational meta-analyses of the primary outcomes. PRIMARY OUTCOMES: Physical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker. RESULTS: In observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI -0.221 to -0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI -0.338 to -0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error. CONCLUSIONS: Our observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach. PMID- 26671951 TI - Long-term risk of cardiovascular and cerebrovascular disease after removal of the colonic microbiota by colectomy: a cohort study based on the Danish National Patient Register from 1996 to 2014. AB - OBJECTIVES: The hypothesis of the study was that if the gut microbiota is involved in the development of atherosclerotic cardiovascular and cerebrovascular diseases (CVDs), total colectomy may reduce the long-term risk of CVDs. The aim was therefore to investigate the risk of CVD in patients after a total colectomy compared with patients undergoing other types of surgery, which are not expected to alter the gut microbiota or the CVD risk. SETTING: The Danish National Patient Register including all hospital discharges in Denmark from 1996 to 2014. PARTICIPANTS: Patients (n=1530) aged 45 years and above and surviving 1000 days after total colectomy without CVDs were selected and matched with five control patients who were also free of CVD 1000 days after other types of surgery. The five control patients were randomly selected from each of the three surgical groups: orthopaedic surgery, surgery in the gastrointestinal tract leaving it intact and other surgeries not related to the gastrointestinal tract or CVD (n=22 950). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the first occurring CVD event in any of the seven diagnostic domains (hypertensive disorders, acute ischaemic heart diseases, chronic ischaemic heart disease, cardiac arrhythmias, heart failure, cerebrovascular diseases and other arterial diseases) and the secondary outcomes were the first occurring event within each of these domains. RESULTS: Estimated by Cox proportional hazard models, the HRs of the composite CVD end point for patients with colectomy compared with the control patients were not significantly reduced (HR=0.94, 95% confidence limits 0.85 to 1.04). Among the seven CVD domains, only the risk of hypertensive disorders was significantly reduced (HR=0.85, 0.73 to 0.98). CONCLUSIONS: Colectomy did not reduce the general risk of CVD, but reduced the risk of hypertensive disorders, most likely due to salt and water depletion induced by colectomy. These results encourage a reappraisal of the associations between gut microbiota and CVD. PMID- 26671952 TI - Protocol for an investigator-blinded, randomised, 3-month, parallel-group study to compare the efficacy of intraoperative tendon sheath irrigation only with both intraoperative and postoperative irrigation in the treatment of purulent flexor tenosynovitis. AB - INTRODUCTION: The management of purulent flexor tenosynovitis of the hand consists of surgical debridement followed by antibiotic treatment. Usually, the debridement is carried out by irrigating the tendon sheath in a proximal to distal direction facilitated by two small incisions. It is unclear whether intraoperative irrigation by itself is adequate for healing or if it should be combined with postoperative irrigation in the ward. The hypothesis of this prospective randomised trial is that intraoperative catheter irrigation alone is as effective as a combination of intraoperative and postoperative intermittent catheter irrigation in the treatment of purulent flexor tenosynovitis. METHODS AND ANALYSIS: In this investigator-blinded, prospective randomised trial, 48 patients suffering from purulent flexor tenosynovitis are randomised in two groups. Intraoperative catheter irrigation of the flexor tendon sheath and antibiotic treatment is identical in both groups, whereas only the patients in one group are subjected to intermittent postoperative catheter irrigation three times a day for 3 days. The primary outcome measure is total active range of movement of the affected finger after 3 months of surgery. The secondary outcome is the need for reoperation. ETHICS AND DISSEMINATION: The research ethics committee of Pirkanmaa Hospital District has approved the study protocol. The protocol has been registered with ClinicalTrials.gov registry (#NCT02320929). All participants will give written informed consent. The study results will elucidate the role of postoperative irrigation, which can be criticised as being labour consuming and unpleasant to the patient. The results of the study will be disseminated as a published article in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02320929; pre-results. PMID- 26671953 TI - Is hypercapnia associated with poor prognosis in chronic obstructive pulmonary disease? A long-term follow-up cohort study. AB - OBJECTIVES: To assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia. SETTING: Patients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres. Follow-up was censored on 31 October 2011. PARTICIPANTS: A total of 275 patients with stable COPD and aged 40 85 years were enrolled. Diagnosis of hypercapnia was confirmed by blood gas analysis. Patients with near-terminal illness or comorbidities that affect PaCO2 (obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded. The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed. OUTCOME MEASURES: Overall survival. RESULTS: Median survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016). Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2 (HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality. CONCLUSIONS: Increased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD. PMID- 26671954 TI - Perceptions of generic medication in the general population, doctors and pharmacists: a systematic review. AB - OBJECTIVE: To investigate negative perceptions about generic medicines and evaluate the proportions of lay people, doctors and pharmacists who hold these perceptions. DESIGN: A systematic review of observational studies. DATA SOURCES: MEDLINE, EMBASE, PsycInfo and Scopus. ELIGIBILITY CRITERIA: Quantitative data from cross-sectional and prospective studies published in English after 1980, using self-report measures to evaluate perceptions about generic medicines, presented as percentages of the total sample assessed. RESULTS: After screening 2737 articles, 52 articles were included in the final analysis. A high proportion of doctors, pharmacists and lay people had negative perceptions of generics. Lay people were significantly more likely to view generics as less effective than branded medication (35.6%, 95% CI 34.8% to 36.4%) compared to doctors (28.7%, 27.5% to 29.9%) and pharmacists (23.6%, 21.2% to 26.2%), p<0.0001. Pharmacists (33.4%, 31.0% to 35.9%) were significantly more likely to believe generics were of inferior quality compared to branded medication than were doctors (28.0%, 26.3% to 29.9%), p=0.0006, and lay people (25.1%, 24.2% to 26.0%), p<0.0001. Doctors believed generics caused more side effects than branded medication (24.4%, 22.2% to 26.9%), compared to pharmacists (17.6%, 15.3% to 20.1%) and lay people (18.8%, 17.8% to 19.8%), p<0.0001. Doctors (28.5%, 26.9% to 30.2%) and pharmacists (25.4%, 21.4% to 29.9%) had significantly more safety concerns about generics than did lay people (18.0%, 17.0% to 19.0%), p <= 0.0002. A greater proportion of lay people felt negatively about generic substitution (34.0%, 33.2% to 34.9%), compared to doctors (24.1%, 22.0% to 26.4%) and pharmacists (11.0%, 9.6% to 12.7%), p<0.0001. Rates of negative perceptions of generics do not appear to have changed substantially over time in the general population or among physician groups, p >= 0.431, but such negative beliefs show a decreasing trend in pharmacists over the study period, p=0.034. CONCLUSIONS: A significant proportion of doctors, pharmacists and lay people hold negative perceptions of generic medicines. It is likely these attitudes present barriers to the wider use of generics. PMID- 26671955 TI - Inequalities in physical comorbidity: a longitudinal comparative cohort study of people with severe mental illness in the UK. AB - OBJECTIVES: Little is known about the prevalence of comorbidity rates in people with severe mental illness (SMI) in UK primary care. We calculated the prevalence of SMI by UK country, English region and deprivation quintile, antipsychotic and antidepressant medication prescription rates for people with SMI, and prevalence rates of common comorbidities in people with SMI compared with people without SMI. DESIGN: Retrospective cohort study from 2000 to 2012. SETTING: 627 general practices contributing to the Clinical Practice Research Datalink, a UK primary care database. PARTICIPANTS: Each identified case (346,551) was matched for age, sex and general practice with 5 randomly selected control cases (1,732,755) with no diagnosis of SMI in each yearly time point. OUTCOME MEASURES: Prevalence rates were calculated for 16 conditions. RESULTS: SMI rates were highest in Scotland and in more deprived areas. Rates increased in England, Wales and Northern Ireland over time, with the largest increase in Northern Ireland (0.48% in 2000/2001 to 0.69% in 2011/2012). Annual prevalence rates of all conditions were higher in people with SMI compared with those without SMI. The discrepancy between the prevalence of those with and without SMI increased over time for most conditions. A greater increase in the mean number of additional conditions was observed in the SMI population over the study period (0.6 in 2000/2001 to 1.0 in 2011/2012) compared with those without SMI (0.5 in 2000/2001 to 0.6 in 2011/2012). For both groups, most conditions were more prevalent in more deprived areas, whereas for the SMI group conditions such as hypothyroidism, chronic kidney disease and cancer were more prevalent in more affluent areas. CONCLUSIONS: Our findings highlight the health inequalities faced by people with SMI. The provision of appropriate timely health prevention, promotion and monitoring activities to reduce these health inequalities are needed, especially in deprived areas. PMID- 26671956 TI - Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time-series study. AB - OBJECTIVES: Low back pain (LBP), from degenerative lumbar spine disease, represents a significant burden on healthcare resources. Studies worldwide report trends attributable to their country's specific demographics and healthcare system. Considering England's specific medico-socioeconomic conditions, we investigate recent trends in hospital admissions and procedures for LBP, and discuss the implications for the allocation of healthcare resources. DESIGN: Retrospective cohort study using Hospital Episode Statistics data relating to degenerative lumbar spine disease in England, between 1999 and 2013. Regression models were used to analyse trends. OUTCOME MEASURES: Trends in the number of admissions and procedures for LBP, mean patient age, gender and length of stay. RESULTS: Hospital admissions and procedures have increased significantly over the study period, from 127.09 to 216.16 and from 24.5 to 48.83 per 100,000, respectively, (p<0.001). The increase was most marked in the oldest age groups with a 1.9 and 2.33-fold increase in admissions for patients aged 60-74 and >= 75 years, respectively, and a 2.8-fold increase in procedures for those aged >= 60 years. Trends in hospital admissions were characterised by a widening gender gap, increasing mean patient age, and decreasing mean hospital stay (p<0.001). Trends in procedures were characterised by a narrowing gender gap, increasing mean patient age (p=0.014) and decreasing mean hospital stay (p<0.001). Linear regression models estimate that each hospital admission translates to 0.27 procedures, per 100,000 (95% CI 0.25 to 0.30, r 0.99, p<0.001; r, Pearson's correlation coefficient). Hospital admissions are increasing at 3.5 times the rate of surgical procedures (regression gradient 7.63 vs 2.18 per 100,000/year). CONCLUSIONS: LBP represents a significant and increasing workload for hospitals in England. These trends demonstrate an increasing demand for specialists involved in the surgical and non-surgical management of this disease, and highlight the need for services capable of dealing with the increased comorbidity burden associated with an ageing patient group. PMID- 26671957 TI - Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population based study (AlertsNet). AB - INTRODUCTION: Bloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed. METHODS AND ANALYSIS: An electronic BC registry established for the German Federal state of Thuringia is the structural basis of this study. The registry includes individual patient data (microbiological results and clinical data) and institutional information for all clinically relevant positive BCs at the participating centres. First, classic result quality indicators for bloodstream infections (eg, sepsis rates) will be studied using Poisson regression models (adjusted for institutional characteristics) in order to derive relative ranks for feedback to clinical institutions. Second, a target value will be established for the process indicator BC rate. On the basis of this target value, recommendations will be made for a given combination of institutional characteristics as a reference for future use in quality control. An interventional study aiming at the improvement of BC rates will be conducted thereafter. On the basis of the results of a survey in the participating institutions, a targeted educational intervention will be developed. The success of the educational intervention will be measured by changes in the process indicator and the result indicators over time using a pre-post design. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics committee of the University Hospital Jena and from the Ethics committee of the State Chamber of Physicians of Thuringia. Findings of AlertsNet will be disseminated through public media releases and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00004825. PMID- 26671958 TI - Estimating the probability of demonstrating vaccine efficacy in the declining Ebola epidemic: a Bayesian modelling approach. AB - OBJECTIVES: We investigate the chance of demonstrating Ebola vaccine efficacy in an individually randomised controlled trial implemented in the declining epidemic of Forecariah prefecture, Guinea. METHODS: We extend a previously published dynamic transmission model to include a simulated individually randomised controlled trial of 100,000 participants. Using Bayesian methods, we fit the model to Ebola case incidence before a trial and forecast the expected dynamics until disease elimination. We simulate trials under these forecasts and test potential start dates and rollout schemes to assess power to detect efficacy, and bias in vaccine efficacy estimates that may be introduced. RESULTS: Under realistic assumptions, we found that a trial of 100,000 participants starting after 1 August had less than 5% chance of having enough cases to detect vaccine efficacy. In particular, gradual recruitment precludes detection of vaccine efficacy because the epidemic is likely to go extinct before enough participants are recruited. Exclusion of early cases in either arm of the trial creates bias in vaccine efficacy estimates. CONCLUSIONS: The very low Ebola virus disease incidence in Forecariah prefecture means any individually randomised controlled trial implemented there is unlikely to be successful, unless there is a substantial increase in the number of cases. PMID- 26671959 TI - Qualitative investigation of patients' experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK. AB - OBJECTIVES: To explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor delivered model. DESIGN: A qualitative investigation using one-to-one interviews before and after patients' appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS). SETTING: A glaucoma clinic based in a tertiary ophthalmic specialist hospital in London. PARTICIPANTS: 43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate. RESULTS: Trust in the patient-provider relationship emerged as a key theme in patients' acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment. CONCLUSIONS: This study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery. PMID- 26671960 TI - Association between self-efficacy, career interest and rural career intent in Australian medical students with rural clinical school experience. AB - OBJECTIVES: To investigate medical student's self-efficacy at the time of finishing their rural clinical school (RCS) placement and factors associated with self-efficacy. Secondary aims are to explore whether interest levels or self efficacy are associated with rural or remote career intentions. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study of medical students who had completed their RCS term in 17 Australian universities. Data were derived from the 2013 Federation of Rural Australian Medical Educators (FRAME) evaluation survey. Questionnaire responses were analysed from 653 medical students from regional Australia. All 732 students who completed their RCS term in 2013 were invited to participate. PRIMARY AND SECONDARY OUTCOME MEASURES: Rural self-efficacy: Six questions to measure self-efficacy beliefs in rural medical practice, based on the sources of self-efficacy described by Bandura. Rural career intention: Students were asked to identify their preferred location for future practice. The options were, Capital or Major City; Inner regional city or large town; Smaller town and very remote area. RESULTS: Questionnaire responses were analysed from 653 medical students from regional Australia (response rate 89.2%). 83.8% of all students recalled an increase in their interest levels for rural medicine as a result of their RCS experience. Actual career intention to work in a regional area or rural area was 60.2%. Bivariate analyses showed female gender (p=0.003), rural background (p<0.001), an RCS preference for clinical training (p<0.001) and general practice intentions (p=0.004) were factors associated with higher levels of self-efficacy. Logistic regression analyses showed that self-efficacy was independently associated with increased interest in rural medicine (OR 1.4 (95% CI 1.3 to 1.5)) and rural career intent (OR 1.2 (95% CI 1.1 to 1.3)). (Model included gender, rural background, preference for RCS, generalist intent, rural practice interest and self-efficacy). CONCLUSIONS: Self-efficacy is associated with increased interest levels for rural medicine and rural medical career intent. PMID- 26671962 TI - Conjoined Twins: Philosophical Problems and Ethical Challenges. AB - We examine the philosophical and ethical issues associated with conjoined twins and their surgical separation. In cases in which there is an extensive sharing of organs, but nevertheless two distinguishable functioning brains, there are a number of philosophical and ethical challenges. This is because such conjoined twins: 1. give rise to puzzles concerning our identity, about whether we are identical to something psychological or biological; 2. force us to decide whether what matters from an ethical point of view is the biological life of our organisms or the existence of our consciousness or mind; 3. raise questions concerning when, if ever, it is morally acceptable to sacrifice one of us to save another; 4. force us to reflect on the conditions for ownership of organs and the justification of removal of organs for transplantation which causes the death of the donor; 5. raise questions about who should take decisions about life-risking treatments when this cannot be decided by patients themselves. We examine and suggest answers to these questions. PMID- 26671961 TI - Physicians' Professionally Responsible Power: A Core Concept of Clinical Ethics. AB - The gathering of power unto themselves by physicians, a process supported by evidence-based practice, clinical guidelines, licensure, organizational culture, and other social factors, makes the ethics of power--the legitimation of physicians' power--a core concept of clinical ethics. In the absence of legitimation, the physician's power over patients becomes problematic, even predatory. As has occurred in previous issues of the Journal, the papers in the 2016 clinical ethics issue bear on the professionally responsible deployment of power by physicians. This introduction explores themes of physicians' power in papers from an international group of authors who address autonomy and trust, the virtues of perinatal hospice, conjoined twins in ethics and law, addiction and autonomy in clinical research on addicting substances, euthanasia of patients with dementia in Belgium, and a pragmatic approach to clinical futility. PMID- 26671964 TI - Factors Associated With Volunteering Among Racial/Ethnic Groups: Findings From the California Health Interview Survey. AB - The present study investigated how volunteering was influenced by individual resources and social capital among four racial/ethnic groups of adults aged 50 and older. The data came from the California Health Interview Survey, a statewide sample that includes non-Hispanic Whites ( n = 18,927), non-Hispanic Asians ( n = 2,428), non-Hispanic Blacks ( n = 1,265), and Hispanics ( n = 3,799). Logistic regression models of volunteering were estimated to explore the effects of human and social capital within and across the racial/ethnic groups. Compared to Whites, racial/ethnic minority adults volunteered less. Although education was a significant predictor of volunteering across all groups, the findings indicated group-specific factors related to human and social capital. Results showed similarities and differences associated with volunteer participation among diverse racial/ethnic groups. The findings underscore the importance of understanding ways of creating inclusive opportunities for civic engagement among an increasingly diverse population. PMID- 26671966 TI - Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia. AB - To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-alpha, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe preeclampsia. These biomarkers could be used to assess podocyte or tubular injury and kidney inflammatory responses during pregnancy and to evaluate postpartum kidney injury recovery in pregnancy-complicated disorders. PMID- 26671967 TI - Disruption of cyclooxygenase type 2 exacerbates apoptosis and renal damage during obstructive nephropathy. AB - Renal oxidative stress is increased in response to ureteral obstruction. In vitro, cyclooxygenase (COX)-2 activity contributes to protection against oxidants. In the present study, we tested the hypothesis that COX-2 activity counters oxidative stress and apoptosis in an in vivo model of obstructive nephropathy. Renal oxidative stress markers, antioxidant enzymes, and markers of tubular injury, tubular dilation, and apoptosis were investigated in COX-2 knockout (COX-2(-/-)) and wild-type (WT) mice subjected to 3 or 7 days of unilateral ureteral obstruction (UUO). In a separate series, WT sham-operated and UUO mice were treated with a selective COX-2 inhibitor, parecoxib. COX-2 increased in response to UUO; the oxidative stress markers 4-hydroxynonenal and nitrotyrosine protein residues increased in kidney tissue with no genotype difference after UUO, whereas the antioxidant enzymes heme oxygenase-1 and SOD2 displayed higher levels in COX-2(-/-) mice. Tubular injury was aggravated by COX 2 deletion, as measured by tubular dilatation, an increase in kidney injury molecule-1, cortical caspase-3 content, and apoptosis index. In conclusion, COX-2 is necessary to protect against tubular injury and apoptosis after UUO but not necessary to protect against oxidative stress. COX-2 is not likely to directly regulate antioxidant enzymes heme oxygenase-1 and SOD in the kidney. PMID- 26671968 TI - Diabetic Insult-Induced Redistribution of MicroRNA in Spatially Organized Mitochondria in Cardiac Muscle. PMID- 26671969 TI - So Far, PCSK9 Inhibitors Work for All Heterozygous FH Patients. PMID- 26671970 TI - Application of Genetic Testing in Hypertrophic Cardiomyopathy for Preclinical Disease Detection. PMID- 26671971 TI - Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model. AB - BACKGROUND: Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model. METHODS AND RESULTS: Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (P<0.005) and a 61% reduction in troponin-T levels (P<0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (P<0.05). CONCLUSIONS: Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury. PMID- 26671973 TI - A nontargeted study of muscle proteome in severely obese women with androgen excess compared with severely obese men and nonhyperandrogenic women. AB - OBJECTIVE: Androgen excess in women is frequently associated with muscle insulin resistance, especially in obese women with polycystic ovary syndrome. However, whether this is a primary event or the result of indirect mechanisms is currently debated. DESIGN: This is an observational study. METHODS: We obtained skeletal muscle biopsies during bariatric surgery from severely obese men (n=6) and women with (n=5) or without (n=5) androgen excess. We used two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of flight/time-of-flight mass spectrometry to identify muscle proteins showing differences in abundance between the groups of obese subjects. RESULTS: Women with hyperandrogenism presented the lowest abundances of glycogen phosphorylase, pyruvate kinase, beta-enolase, glycerol-3-phosphate dehydrogenase, creatine kinase M-type, and desmin, whereas the abundances of these molecules were similar in control women and men. CONCLUSION: According to our nontargeted proteomic approach, women with hyperandrogenism show a specific alteration of the skeletal muscle proteome that could contribute to their insulin resistance. Because men do not show similar results, this alteration does not appear to be the direct effect on muscle of androgen excess, but rather the consequence of indirect mechanisms that merit further studies. PMID- 26671972 TI - Longitudinal plasma metanephrines preceding pheochromocytoma diagnosis: a retrospective case-control serum repository study. AB - OBJECTIVE: Plasma metanephrines (PMN) are highly sensitive for diagnosis of pheochromocytoma, but the natural history of PMN before pheochromocytoma diagnosis has not been previously described. The aim of the study was to compare the progression of PMN before pheochromocytoma diagnosis to matched healthy and essential hypertension disease controls. DESIGN: A retrospective case-control Department of Defense Serum Repository (DoDSR) study. METHODS: We performed a DoDSR study that compared three longitudinal pre-diagnostic PMN for 30 biopsy proven pheochromocytoma cases to three longitudinal PMN for age, sex, race, and age of serum sample matched healthy and essential hypertension disease controls. Predominant metanephrine (MN) or normetanephrine (NMN) production was identified for each case and converted to a percentage of the upper limit of normal to allow analysis of all cases together. PMN were measured by Quest Diagnostics. RESULTS: The predominant plasma metanephrine (PPM) was >100 and 300% of the upper limit of normal a median of 6.6 and 4.1 years before diagnosis respectively. A greater percentage of pheochromocytoma patients had a PPM >100 and >300% of the upper limit of normal compared with combined healthy and essential hypertension disease controls <2, 2-8, and >8 years prior to diagnosis. For patients with a baseline PPM 90-300% of the upper limit of normal, a 25% rate of rise per year was 100% specific for pheochromocytoma. CONCLUSIONS: PPMs elevate years before diagnosis which suggests that delayed diagnoses are common. For mild PMN elevations, follow up longitudinal PMN trends may provide a highly specific and economical diagnostic tool. PMID- 26671974 TI - Neuroendocrine tumors producing calcitonin: characteristics, prognosis and potential interest of calcitonin monitoring during follow-up. AB - OBJECTIVES: Inappropriate calcitonin (CT) release, a major feature of medullary thyroid cancer (MTC), may occur in neuroendocrine tumors (NETs). The aims of this retrospective study were to assess i) the characteristics and prognosis of CT producing NETs, and ii) the value of CT monitoring during follow-up. METHODS: All patients with NETs in whom serum CT was assayed between 2010 and 2012 were included. MTCs were excluded. Clinical, biological, and histological characteristics were studied. RESULTS: Twenty-one (12%) of 176 patients in whom serum CT was systematically assayed had concentrations >100 ng/l, with tumours predominantly of bronchial or pancreatic origin (P<0.0001), and of high grade (P=0.0006). Poor prognosis was linked to high CT levels, poor differentiation, and grade 3. In a total group of 24 patients with serum CT >100 ng/l, symptoms potentially attributable to CT were recorded in eight, with occasional overlap with the carcinoid syndrome among other secretory syndromes. Immunohistochemistry could be performed in six tumor specimens, CT being detected in five. In 11 patients with five or more successive CT assays, hormone levels were fairly well correlated with clinical courses. CONCLUSION: Serum CT levels may be raised in some patients with NETs, especially from foregut origin, and of high grade. The suggested value of CT monitoring during follow-up must be confirmed in further studies. PMID- 26671976 TI - Compensatory function of the remaining testis is dissociated in boys and adolescents with monorchidism. AB - OBJECTIVE: Compensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad. DESIGN: In a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months-18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Mullerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells. RESULTS: In the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged <3 and >13 years. Serum testosterone and LH did not differ significantly between patients and controls. CONCLUSION: In boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls. PMID- 26671975 TI - Association of mitotane with chylomicrons and serum lipoproteins: practical implications for treatment of adrenocortical carcinoma. AB - OBJECTIVE: Oral mitotane (o,p'-DDD) is a cornerstone of medical treatment for adrenocortical carcinoma (ACC). AIM: Serum mitotane concentrations >14 mg/l are targeted for improved efficacy but not achieved in about half of patients. Here we aimed at a better understanding of intestinal absorption and lipoprotein association of mitotane and metabolites o,p'-dichlorodiphenylacetic acid (o,p' DDA) and o,p'-dichlorodiphenyldichloroethane (o,p'-DDE). DESIGN: Lipoproteins were isolated by ultracentrifugation from the chyle of a 29-year-old patient and serum from additional 14 ACC patients treated with mitotane. HPLC was applied for quantification of mitotane and metabolites. We assessed NCI-H295 cell viability, cortisol production, and expression of endoplasmic reticulum (ER) stress marker genes to study the functional consequences of mitotane binding to lipoproteins. RESULTS: Chyle of the index patient contained 197 mg/ml mitotane, 53 mg/ml o,p' DDA, and 51 mg/l o,p'-DDE. Of the total mitotane in serum, lipoprotein fractions contained 21.7+/-21.4% (VLDL), 1.9+/-0.8% (IDL), 8.9+/-5.5% (LDL1), 18.9+/-9.6% (LDL2), 10.1+/-4.0% (LDL3), and 26.3+/-13.0% (HDL2). Only 12.3+/-5.5% were in the lipoprotein-depleted fraction. DISCUSSION: Mitotane content of lipoproteins directly correlated with their triglyceride and cholesterol content. O,p'-DDE was similarly distributed, but 87.9+/-4.2% of o,p'-DDA found in the HDL2 and lipoprotein-depleted fractions. Binding of mitotane to human lipoproteins blunted its anti-proliferative and anti-hormonal effects on NCI-H295 cells and reduced ER stress marker gene expression. CONCLUSION: Mitotane absorption involves chylomicron binding. High concentrations of o,p'-DDA and o,p'-DDE in chyle suggest intestinal mitotane metabolism. In serum, the majority of mitotane is bound to lipoproteins. In vitro, lipoprotein binding inhibits activity of mitotane suggesting that lipoprotein-free mitotane is the therapeutically active fraction. PMID- 26671977 TI - Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer. AB - OBJECTIVE: Our objective was to evaluate the efficacy and safety of sunitinib following at least one course of radioactive iodine treatment in patients with advanced differentiated thyroid cancer (DTC). The study endpoints included best response rate (including best objective response rate) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, measurement of serum thyroglobulin (Tg), and toxicity evaluation. DESIGN AND METHODS: This was a single center, nonrandomized, open-label, phase 2 clinical trial. In total, 23 patients were enrolled and were treated with a starting daily, oral dose of 37.5 mg sunitinib. Patients were evaluated with imaging, laboratory tests, and physical examination periodically per protocol. RESULTS: The mean best response was a decrease of 17.2% (S.D. 22.8) in tumor sum from baseline. Six (26%) patients achieved a partial response (PR), and 13 (57%) had stable disease (SD) for a clinical benefit rate (PR+SD) of 83%. The overall median PFS was 241 days (interquartile limits, 114-518). No statistically significant difference was observed between the medians of the baseline and post treatment Tg values (P=0.24). The most common adverse events included grades 1 and 2 decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension. CONCLUSIONS: These data demonstrate that sunitinib exhibits significant anti tumor activity in patients with advanced DTC. Since sunitinib was relatively well tolerated, there is the potential for clinical benefit in these patients, and further investigation of this agent is warranted. PMID- 26671978 TI - Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart. AB - RATIONALE: Alternative cleavage and polyadenylation (APA) of mRNA represents a layer of gene regulation that to date has remained unexplored in the heart. This phenomenon may be relevant, as the positioning of the poly(A) tail in mRNAs influences the length of the 3'-untranslated region (UTR), a critical determinant of gene expression. OBJECTIVE: To investigate whether the 3'UTR length is regulated by APA in the human heart and whether this changes in the failing heart. METHODS AND RESULTS: We used 3'end RNA sequencing (e3'-Seq) to directly measure global patterns of APA in healthy and failing human heart specimens. By monitoring polyadenylation profiles in these hearts, we identified disease specific APA signatures in numerous genes. Interestingly, many of the genes with shortened 3'UTRs in heart failure were enriched for functional groups such as RNA binding, whereas genes with longer 3'UTRs were enriched for cytoskeletal organization and actin binding. RNA sequencing in a larger series of human hearts revealed that these APA candidates are often differentially expressed in failing hearts, with an inverse correlation between 3'UTR length and the level of gene expression. Protein levels of the APA regulator, poly(A)-binding protein nuclear 1 were substantially downregulated in failing hearts. CONCLUSIONS: We provide genome-wide, high-resolution polyadenylation maps of the human heart and show that the 3'end formation of mRNA is dynamic in heart failure, suggesting that APA mediated 3'UTR length modulation represents an additional layer of gene regulation in failing hearts. PMID- 26671980 TI - How to Define Hypertension in Children and Adolescents. PMID- 26671979 TI - Establishing International Blood Pressure References Among Nonoverweight Children and Adolescents Aged 6 to 17 Years. AB - BACKGROUND: Several distributions of country-specific blood pressure (BP) percentiles by sex, age, and height for children and adolescents have been established worldwide. However, there are no globally unified BP references for defining elevated BP in children and adolescents, which limits international comparisons of the prevalence of pediatric elevated BP. We aimed to establish international BP references for children and adolescents by using 7 nationally representative data sets (China, India, Iran, Korea, Poland, Tunisia, and the United States). METHODS AND RESULTS: Data on BP for 52 636 nonoverweight children and adolescents aged 6 to 19 years were obtained from 7 large nationally representative cross-sectional surveys in China, India, Iran, Korea, Poland, Tunisia, and the United States. BP values were obtained with certified mercury sphygmomanometers in all 7 countries by using standard procedures for BP measurement. Smoothed BP percentiles (50th, 90th, 95th, and 99th) by age and height were estimated by using the Generalized Additive Model for Location Scale and Shape model. BP values were similar between males and females until the age of 13 years and were higher in males than females thereafter. In comparison with the BP levels of the 90th and 95th percentiles of the US Fourth Report at median height, systolic BP of the corresponding percentiles of these international references was lower, whereas diastolic BP was similar. CONCLUSIONS: These international BP references will be a useful tool for international comparison of the prevalence of elevated BP in children and adolescents and may help to identify hypertensive youths in diverse populations. PMID- 26671982 TI - Knock-in(g) RAF for a loop. PMID- 26671981 TI - Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling. AB - Receptor organization and dynamics at the cell membrane are important factors of signal transduction regulation. Using super-resolution microscopy and single particle tracking, we show how the negative coreceptor CD22 works with the cortical cytoskeleton in restraining BCR signalling. In naive B cells, we found endogenous CD22 to be highly mobile and organized into nanodomains. The landscape of CD22 and its lateral diffusion were perturbed either in the absence of CD45 or when the CD22 lectin domain was mutated. To understand how a relatively low number of CD22 molecules can keep BCR signalling in check, we generated Brownian dynamic simulations and supported them with ex vivo experiments. This combined approach suggests that the inhibitory function of CD22 is influenced by its nanoscale organization and is ensured by its fast diffusion enabling a "global BCR surveillance" at the plasma membrane. PMID- 26671983 TI - Increased Expression and Cellular Localization of P2X7R in Cortical Lesions of Patients With Focal Cortical Dysplasia. AB - Focal cortical dysplasias (FCDs) are major brain malformations that commonly lead to medically intractable epilepsy. The purinergic ionotropic P2X7 receptor (P2X7R) is an atypical P2X subtype that gates calcium and sodium ions. Previous animal studies have suggested that P2X7R is a contributing factor in epileptogenesis. This study aimed to define the distribution and expression of P2X7R in 35 FCD patient-surgical-resection specimens relative to autopsy control samples (n = 8). Immunohistochemical colocalization assays revealed that P2X7R was primarily expressed in neurons, astrocytes, and microglia. In FCD samples, P2X7R protein levels were increased in abnormal cell types such as dysmorphic neurons and balloon cells, which are characteristic of FCD. By real-time PCR and Western blotting, P2X7R mRNA and protein expression levels were elevated in FCD patient samples vs control samples; P2X7R expression was also higher in FCDII vs FCDIa patient samples. Because interleukin-1beta is a downstream factor of the P2X7R signaling pathway, we determined that there was also moderate-to-strong interleukin-1beta expression in the dysmorphic neurons, balloon cells, and microglia in FCD patient lesions. These results indicate that increasing P2X7R levels may contribute to the pathogenesis of human FCD and that P2X7R represents a potential anti-epileptogenic target. PMID- 26671984 TI - Neuropathological Characteristics of Brachial Plexus Avulsion Injury With and Without Concomitant Spinal Cord Injury. AB - Neonatal brachial plexus avulsion injury (BPAI) commonly occurs as a consequence of birth trauma and can result in lifetime morbidity; however, little is known regarding the evolving neuropathological processes it induces. In particular, mechanical forces during BPAI can concomittantly damage the spinal cord and may contribute to outcome. Here, we describe the functional and neuropathological outcome following BPAI, with or without spinal cord injury, in a novel pediatric animal model. Twenty-eight-day-old piglets underwent unilateral C5-C7 BPAI with and without limited myelotomy. Following avulsion, all animals demonstrated right forelimb monoparesis. Injury extending into the spinal cord conferred greater motor deficit, including long tract signs. Consistent with clinical observations, avulsion with myelotomy resulted in more severe neuropathological changes with greater motor neuron death, progressive axonopathy, and persistent glial activation. These data demonstrate neuropathological features of BPAI associated with poor functional outcome. Interestingly, in contrast to adult small animal models of BPAI, a degree of motor neuron survival was observed, even following severe injury in this neonatal model. If this is also the case in human neonatal BPAI, repair may permit functional restoration. This model also provides a clinically relevant platform for exploring the complex postavulsion neuropathological responses that may inform therapeutic strategies. PMID- 26671986 TI - The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. AB - A number of key mutations that affect treatment and prognosis have been identified in human gliomas. Two major ways to identify these mutations in a tumor sample are direct interrogation of the mutated DNA itself and immunohistochemistry to assess the effects of the mutated genes on proteins. Immunohistochemistry is an affordable, robust, and widely available technology that has been in place for decades. For this reason, the use of immunohistochemical approaches to assess molecular genetic changes has become an essential component of state-of-the-art practice. In contrast, even though DNA sequencing technologies are undergoing rapid development, many medical centers do not have access to such methodologies and may be thwarted by the relatively high costs of sending out such tests to reference laboratories. This review summarizes the current experience using immunohistochemistry of glioma samples to identify mutations in IDH1, TP53, ATRX, histone H3 genes, BRAF, EGFR, MGMT, CIC, and FUBP1 as well as guidelines for prudent use of DNA sequencing as a supplemental method. PMID- 26671985 TI - Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy. AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. PMID- 26671987 TI - Diffusion Tensor Imaging for Assessing Brain Gray and White Matter Abnormalities in a Feline Model of alpha-Mannosidosis. AB - alpha-Mannosidosis (AMD) is an autosomal recessively inherited lysosomal storage disorder affecting brain function and structure. We performed ex vivo and in vivo diffusion tensor imaging (DTI) on the brains of AMD-affected cats to assess gray and white matter abnormalities. A multi-atlas approach was used to generate a brain template to process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity values from gray and white matter regions from ex vivo DTI. Regional analysis from various regions of the gray matter (frontal cortex, cingulate gyrus, caudate nucleus, hippocampus, thalamus, and occipital cortex), and white matter (corpus callosum, corticospinal tract, cerebral peduncle, external and internal capsule) was also performed on both ex vivo and in vivo DTI. Ex vivo DTI revealed significantly reduced FA from both gray and white matter regions in AMD-affected cats compared to controls. Significantly reduced FA was also observed from in vivo DTI of AMD-affected cats compared to controls, with lower FA values observed in all white matter regions. We also observed significantly increased axial and radial diffusivity values in various gray and white matter regions in AMD cats from both ex vivo and in vivo DTI data. Imaging findings were correlated with histopathologic analyses suggesting that DTI studies can further aid in the characterization of AMD by assessing the microstructural abnormalities in both white and gray matter. PMID- 26671988 TI - Synaptic lipids in cortical function and psychiatric disorders. PMID- 26671990 TI - Evaluation of masticatory parameters in overweight and obese children. AB - OBJECTIVES: Mastication is an essential function that prepares the food for swallowing and digestion and may be related to nutritional status. Thus, the aims of this study were to evaluate the masticatory parameters in overweight and obese children and the relation between bite force and anthropometric evaluation, food consistency, breast/bottle-feeding, and occlusion. MATERIALS AND METHODS: The sample consisted of 204 children of both genders, age range 8-10 years, divided into normal weight, overweight, and obese. Unilateral bite force was measured using a digital gnatodynamometer with 10mm force fork. Anthropometric and nutritional evaluation involved the measurements of body mass index and skeletal muscle mass using bioelectric impedance analysis. Occlusion was evaluated as regards orthodontic treatment need and food consistency was analysed using a structured questionnaire. In addition, the time of breast- and bottle-feeding was investigated. The results were submitted to chi-square and correlation tests, analysis of variance, and multiple linear regression to determine the relation between bite force and the independent variables under study (alpha = 0.05). RESULTS: Statistical analysis showed that the time of breast- and bottle-feeding and food consistency did not differ among groups. The regression model showed that body mass index, orthodontic treatment need, and body skeletal muscle mass contributed significantly to the variation in bite force. CONCLUSIONS: Breast- and bottle-feeding behaviour and food consistency did not differ in normal weight, overweight, and obese children. However, bite force was dependent on body skeletal muscle mass, body mass index, and orthodontic treatment need. PMID- 26671989 TI - Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP. AB - Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases. PMID- 26671992 TI - The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer. AB - PURPOSE: The transition of prostate adenocarcinoma to a predominantly androgen receptor (AR) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression +/- the development of small cell or neuroendocrine tumor characteristics. As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning toward a neuroendocrine phenotype (NEPC). EXPERIMENTAL DESIGN: We prospectively studied a metastatic tumor biopsy, serum biomarkers, and circulating tumor cells (CTC, Epic Sciences) from patients with castration-resistant prostate cancer (CRPC) including those with pure or mixed NEPC histology present on biopsy. CTCs labeled with the patient's clinical status were used to learn features that discriminate NEPC patients, which was then applied to an independent cohort. RESULTS: Twenty-seven patients with CRPC including 12 NEPC and 5 with atypical clinical features suggestive of NEPC transition were studied. CTCs from NEPC patients demonstrated frequent clusters, low or absent AR expression, lower cytokeratin expression, and smaller morphology relative to typical CRPC. A multivariate analysis of protein and morphologic variables enabled distinguishing CTCs of NEPC from CRPC. This CTC classifier was applied to an independent prospective cohort of 159 metastatic CRPC patients and identified in 17/159 (10.7%) of cases, enriched in patients with high CTC burden (P < 0.01) and visceral metastases (P = 0.04). CONCLUSIONS: CTCs from patients with NEPC have unique morphologic characteristics, which were also identified in a subset of CRPC patients with aggressive clinical features potentially undergoing NEPC transition. PMID- 26671993 TI - SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non-Small Cell Lung Cancer. AB - PURPOSE: Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from platinum-based chemotherapy. We hypothesized that decreased expression of SMARCA4/BRG1, a known regulator of transcription and DNA repair, is a novel predictive biomarker of increased sensitivity to adjuvant platinum-based therapies in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: The prognostic value was tested using a gene expression microarray from the Director's Challenge Lung Study (n = 440). The predictive significance of SMARCA4 was determined using a gene-expression microarray (n = 133) from control and treatment arms of the JBR.10 trial of adjuvant cisplatin/vinorelbine. Kaplan-Meier method and log-rank tests were used to estimate and test the differences of probabilities in overall survival (OS) and disease-specific survival (DSS) between expression groups and treatment arms. Multivariate Cox regression models were used while adjusting for other clinical covariates. RESULTS: In the Director's Challenge Study, reduced expression of SMARCA4 was associated with poor OS compared with high and intermediate expression (P < 0.001 and P = 0.009, respectively). In multivariate analysis, compared with low, high SMARCA4 expression predicted a decrease in risk of death [HR, 0.6; 95% confidence interval (CI), 0.4-0.8; P = 0.002]. In the JBR.10 trial, improved 5-year DSS was noted only in patients with low SMARCA4 expression when treated with adjuvant cisplatin/vinorelbine [HR, 0.1; 95% CI, 0.0-0.5, P = 0.002 (low); HR, 1.0; 95% CI, 0.5-2.3, P = 0.92 (high)]. An interaction test was highly significant (P = 0.01). CONCLUSIONS: Low expression of SMARCA4/BRG1 is significantly associated with worse prognosis; however, it is a novel significant predictive biomarker for increased sensitivity to platinum-based chemotherapy in NSCLC. Clin Cancer Res; 22(10); 2396-404. (c)2015 AACR. PMID- 26671994 TI - Molecular Pathways: Targeting Cancer Stem Cells Awakened by Chemotherapy to Abrogate Tumor Repopulation. AB - Cytotoxic chemotherapy remains the first-line therapy for many advanced solid tumors; hence, understanding the underlying mechanisms to overcome chemoresistance remains a top research priority. In the clinic, chemotherapy is administered in multiple cycles that are spaced out to allow the recovery or repopulation of normal tissues and tissue stem cells between treatment cycles. However, residual surviving cancer cells and cancer stem cells can also repopulate tumors during the gap periods between chemotherapy cycles. Tumor repopulation is a phenomenon that has not been well studied; it is often overlooked due to current customized experimental study strategies. Recent findings reveal an alarming role for dying cells targeted by chemotherapy in releasing mitogens to stimulate active repopulation of quiescent cancer stem cells. Therefore, new therapeutic options to abrogate tumor repopulation will provide new avenues to improve chemotherapeutic response and clinical outcome. PMID- 26671995 TI - The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase. AB - PURPOSE: ABTL0812 is a novel first-in-class, small molecule which showed antiproliferative effect on tumor cells in phenotypic assays. Here we describe the mechanism of action of this antitumor drug, which is currently in clinical development. EXPERIMENTAL DESIGN: We investigated the effect of ABTL0812 on cancer cell death, proliferation, and modulation of intracellular signaling pathways, using human lung (A549) and pancreatic (MiaPaCa-2) cancer cells and tumor xenografts. To identify cellular targets, we performed in silico high throughput screening comparing ABTL0812 chemical structure against ChEMBL15 database. RESULTS: ABTL0812 inhibited Akt/mTORC1 axis, resulting in impaired cancer cell proliferation and autophagy-mediated cell death. In silico screening led us to identify PPARs, PPARalpha and PPARgamma as the cellular targets of ABTL0812. We showed that ABTL0812 activates both PPAR receptors, resulting in upregulation of Tribbles-3 pseudokinase (TRIB3) gene expression. Upregulated TRIB3 binds cellular Akt, preventing its activation by upstream kinases, resulting in Akt inhibition and suppression of the Akt/mTORC1 axis. Pharmacologic inhibition of PPARalpha/gamma or TRIB3 silencing prevented ABTL0812-induced cell death. ABTL0812 treatment induced Akt inhibition in cancer cells, tumor xenografts, and peripheral blood mononuclear cells from patients enrolled in phase I/Ib first-in-human clinical trial. CONCLUSIONS: ABTL0812 has a unique and novel mechanism of action, that defines a new and drugable cellular route that links PPARs to Akt/mTORC1 axis, where TRIB3 pseudokinase plays a central role. Activation of this route (PPARalpha/gamma-TRIB3-Akt-mTORC1) leads to autophagy mediated cancer cell death. Given the low toxicity and high tolerability of ABTL0812, our results support further development of ABTL0812 as a promising anticancer therapy. Clin Cancer Res; 22(10); 2508-19. (c)2015 AACR. PMID- 26671996 TI - Profiling Non-Small Cell Lung Cancer: From Tumor to Blood. AB - Circulating cell-free tumor DNA has shown great promise for noninvasive genomic profiling to guide the administration of targeted therapies in non-small cell lung cancer. With advancements in molecular technology, it is now possible to interrogate multiple clinically actionable genetic drivers in the blood with a single assay. PMID- 26671998 TI - Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis. AB - Type 2 cannabinoid receptor (CB2) has been proposed to play a pivotal role in meiotic entry of male germ cells, similar to retinoic acid (RA). In this study, we showed that activation of CB2with the specific agonist JWH133 [3-(1',1' dimethylbutyl)-1-deoxy-8-THC] (IC5010(-6)M) mimics epigenetic events induced by RA (IC5010(-7)M) in spermatogonia. Both JWH133 and RA treatments stimulate the expression of the meiotic genes c-KitandStra8, by up-regulating H3K4me3 and down regulating H3K9me2 levels in genomic regions flanking the transcription start site. Moreover, both agents increase the expression ofPrdm9, the gene encoding a meiosis-specific histone, H3K4me3 methyltransferase, which marks hotspots of recombination in prophase I, thus resulting in a global increase in H3K4me3. Notably, prolonged administration of JWH133 to immature 7 dpp CD-1 mice induced an acceleration of the onset of spermatogenesis, whereas the specific CB2antagonist delayed germ cell differentiation. Thus, both hyper- and hypostimulation of CB2disrupted the temporal dynamics of the spermatogenic cycle. These findings highlight the importance of proper CB2signaling for the maintenance of a correct temporal progression of spermatogenesis and suggest a possible adverse effect of cannabis in deregulating this process.-Di Giacomo, D., De Domenico, E., Sette, C., Geremia, R., Grimaldi, P. Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis. PMID- 26671997 TI - GHRH excess and blockade in X-LAG syndrome. AB - X-linked acrogigantism (X-LAG) syndrome is a newly described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated GH and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GHRH levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(d-Arg(2))-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome. PMID- 26672000 TI - Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters. AB - Understanding the regulation of the stem cell fate is fundamental for designing novel regenerative medicine strategies. Previous studies have suggested that pharmacological treatments with small molecules provide a robust and reversible regulation of the stem cell program. Previously, we showed that treatment with a vanadium compound influences muscle cell fatein vitro In this study, we demonstrate that treatment with the phosphotyrosine phosphatase inhibitor bisperoxovanadium (BpV) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regenerationin vivofollowing transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self renewal potentialin vivoand replenished the niche in both satellite and interstitial cell compartments. Moreover, we found that BpV treatment induces specific activating chromatin modifications at the promoter regions of genes associated with stem cell fate, includingSca-1andPw1 Thus, our findings indicate that BpV resets the cell fate program by specific epigenetic regulations, such that the committed myogenic cell fate is redirected to an earlier progenitor cell fate stage, which leads to an enhanced regenerative stem cell potential. Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouche, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functionsviaepigenetic modulation of Sca-1 and Pw1 promoters. PMID- 26672002 TI - The effect of introducing routine self-taken extra-genital swabs in a genitourinary medicine clinic cohort: a before and after study. AB - Starting July 2013, all patients attending a sexual health clinic who reported risk of extra-genital infection were offered self-taken extra-genital swabs. The study aim was to assess the detection rate of extra-genital infection since self taken swabs were introduced. We compared patients diagnosed with chlamydia and gonorrhoea in six-month periods before (February-July 2012) and after (February July 2014) the introduction of self-taken extra-genital swabs. There were 408 (98 gonorrhoea, 310 chlamydia) detected infections in the 2012 period and 404 (121 gonorrhoea, 283 chlamydia) in 2014. The rate of extra-genital chlamydia/gonorrhoea increased fourfold from 18/408, 4.4% to 77/404 19% (P < 0.0001). The rise was seen in both rectal (8/408, 2% vs. 40/404, 9.9%, P < 0.0001) and pharyngeal infection (10/408, 2.5% vs. 48/404, 11.8% P < 0.0001). Significant rises were seen in men who have sex with men in rectal (5/408, 1.2% vs. 28/404, 6.9% P = 0.001) and pharyngeal infection (10/408, 2.5% vs. 20/404, 5%, P = 0.02) and for women in rectal (3/408, 0.7% vs. 12/404, 3% P = 0.03) and pharyngeal infection (0/408, 0% vs. 20/404, 5%, P < 0.0001). In 100 consecutive patients having extra-genital swabs in each study period, self-swabbing rose from 0% (0/100) to 89% (89/100) P < 0.0001. The introduction of routine self-taken extra-genital swabs has led to a large rise in detected extra-genital chlamydia and/or gonorrhoea infection in men who have sex with men and women. PMID- 26671999 TI - Retinol as a cofactor for PKCdelta-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. AB - We previously defined that the mitochondria-localized PKCdelta signaling complex stimulates the conversion of pyruvate to acetyl-coenzyme A by the pyruvate dehydrogenase complex. We demonstrated in vitro and ex vivo that retinol supplementation enhances ATP synthesis in the presence of the PKCdelta signalosome. Here, we tested in vivo if a persistent oversupply of retinol would further impair glucose metabolism in a mouse model of diet-induced insulin resistance. We crossed mice overexpressing human retinol-binding protein (hRBP) under the muscle creatine kinase (MCK) promoter (MCKhRBP) with the PKCdelta(-/-) strain to generate mice with a different status of the PKCdelta signalosome and retinoid levels. Mice with a functional PKCdelta signalosome and elevated retinoid levels (PKCdelta(+/+)hRBP) developed the most advanced stage of insulin resistance. In contrast, elevation of retinoid levels in mice with inactive PKCdelta did not affect remarkably their metabolism, resulting in phenotypic similarity between PKCdelta(-/-)hRBP and PKCdelta(-/-) mice. Therefore, in addition to the well-defined role of PKCdelta in the etiology of metabolic syndrome, we present a novel PKCdelta signaling pathway that requires retinol as a metabolic cofactor and is involved in the regulation of fuel utilization in mitochondria. The distinct role in whole-body energy homeostasis establishes the PKCdelta signalosome as a promising target for therapeutic intervention in metabolic disorders. PMID- 26672003 TI - Prevalence of anaemia among HIV patients in rural China during the HAART era. AB - The prevalence of anaemia among HIV patients receiving highly active antiretroviral therapy (HAART) in China has not been extensively studied. The purpose of this study was to estimate the prevalence of anaemia among HIV patients receiving HAART in China. This cross-sectional study was conducted based on data in routine record registers. Factors associated with anaemia were evaluated by logistic regression model. Among the 8632 HIV patients in this analysis, the overall prevalence of anaemia was 39.2%, and the prevalence of mild, moderate, and severe anaemia were 27.2%, 10.8%, and 1.2%, respectively. Anaemia was more prevalence among male, older, little time taken HAART and lower CD4 cell count. Patients taken TCM had lower prevalence of anaemia. The prevalence of anaemia among the HIV patients receiving HAART was high in this study. HIV patients with anaemia who are older and have CD4 cells count lower than 200 cells/mL require more attention. Traditional Chinese medicine may be a potential method to lower the frequency of anaemia. PMID- 26672004 TI - Heterogeneity of community-based voluntary, counselling and testing services for HIV in Europe: the HIV-COBATEST survey. AB - This study reports the first EU-wide survey of community-based voluntary counselling and testing services (CBVCTs), with the following aims: to assess the current availability of CBVCTs and how the concept of CBVCT is understood; to describe CBVCT modalities and strategies; and to measure the use of rapid tests within CBVCTs. A cross-sectional survey was conducted in two different key informant groups: HIV/AIDS National Focal Points (NFPs) and CBVCTs from the EU and European Free Trade Association (EFTA) countries. A definition of CBVCTs was reached. Descriptive and correspondence analyses were performed. The COBATEST survey was answered by NFPs from 25 of the 32 EU/EFTA countries (response rate of 78.1%), and by 55 CBVCTs in 22 different countries. CBVCTs were functioning in nearly all the responding countries, but only 56% explicitly included them in their national strategic plans. In those that had CBVCTs, the NFPs often lacked reliable information on CBVCTs. In general, CBVCTs in Europe are focused mainly on men who have sex with men, are primarily peer-driven and highly communitarised, whereas CBVCTs targeting other at-risk populations are more medicalised. In addition, the oral test is under-used and in general test performance is highly medicalised. Results show that there is a wide heterogeneity of CBVCTs in Europe, which is varied and highly medicalised. The data provided in this study in conjunction with other deliverables produced by the COBATEST project should contribute to the development of standardised indicators to enable comparisons over time and eventually improve the effectiveness of CBVCTs across Europe. PMID- 26672005 TI - Dr Evelyn Gillan. PMID- 26672006 TI - Detection and management of the first human anthrax outbreak in Togo. AB - OBJECTIVE: The aim of this study was to describe and define an outbreak of human anthrax in two villages in the northern savannah region of Togo. PATIENTS AND METHOD: In December 2009, localised groups of deaths occurred among villagers and their livestock, confirmed to be due to anthrax at the district hospital of Dapaong in Northern Togo. The National Disease Control department undertook an investigation to describe the epidemiological, clinical and bacteriological characteristics of this outbreak. RESULTS: Thirty-four individuals presented with clinical manifestations of anthrax. All patients were known to have consumed meat from cattle who had died of unknown causes or had been killed as a result of unknown illness. All patients presented with muco-cutaneous lesions; some had gastro-intestinal, neurological or meningeal symptoms, or septicaemia. One patient was co-infected with Plasmodium falciparum. Six deaths (17.6%) were reported at the beginning of the epidemic; 28 patients were successfully treated with a 10-day course of intravenous Penicillin or oral Amoxicillin. The two factors that contributed to the ultimate resolution of the anthrax outbreak were the increase of community awareness toward health promotion and vaccination of all farm animals. CONCLUSION: Although six deaths occurred among families' members who were infected, new human anthrax cases were prevented by rapid treatment of victims as well as aggressive public health interventions. However the risk of re-emergence of infection and exposure still exists as there are no existing epidemiological mapping and no identification of infected zones; and furthermore, no functional anthrax surveillance system exists in the affected region. PMID- 26672007 TI - Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study. AB - OBJECTIVE: A retrospective study was performed to compare the difference in platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), between cirrhotic patients with and without acute upper gastrointestinal bleeding (AUGIB) or acute oesophageal variceal bleeding (AEVB). METHODS: Between January 2012 and June 2014, a total of 1734 cirrhotic patients were enrolled and were classified into 'AUGIB' (n = 497) and 'no AUGIB' (n = 1237) groups according to their disease history. They were further divided into 'AEVB' (n = 297) and 'no AEVB' (n = 1259) groups according to the endoscopic findings. Additionally, 178 patients with AUGIB were not assigned to either the 'AEVB' or 'no AEVB' groups due to the absence of any endoscopic findings. RESULTS: Compared with the 'no AUGIB' group, the 'AUGIB' group had similar PLT (99.99 +/- 89.90 vs.101.47 +/- 83.03; P = 0.734) and APTT (42.96 +/- 15.20 vs.43.77 +/- 11.01; P = 0.219), but significantly higher PT (17.30 +/- 5.62 vs.16.03 +/- 4.68; P < 0.001) and INR (1.45 +/- 0.69 vs.1.31 +/- 0.59; P < 0.001). A lower PT was independently associated with the absence of AUGIB (OR = 0.968; 95% CI: 0.942-0.994). Compared with the 'no AEVB' group, the 'AEVB' group had significantly lower PLT (86.87 +/- 62.14 vs.101.74 +/- 83.62; P = 0.004) and APTT (40.98 +/- 7.9 vs.43.72 +/- 10.97; P < 0.001), but similar PT (16.53 +/- 3.71 vs.16.04 +/- 4.68; P = 0.088) and INR (1.35 +/- 0.41 vs.1.31 +/- 0.59; P = 0.225). A higher PLT was independently associated with the absence of AEVB (OR = 1.004; 95% CI: 1.002-1.006; P = 0.001). CONCLUSIONS: PLT was associated with the occurrence of portal hypertension related bleeding in liver cirrhosis. PMID- 26672008 TI - Contrasting Genomic Diversity in Two Closely Related Postharvest Pathogens: Penicillium digitatum and Penicillium expansum. AB - Penicillium digitatum and Penicillium expansum are two closely related fungal plant pathogens causing green and blue mold in harvested fruit, respectively. The two species differ in their host specificity, being P. digitatum restricted to citrus fruits and P. expansum able to infect a wide range of fruits after harvest. Although host-specific Penicillium species have been found to have a smaller gene content, it is so far unclear whether these different host specificities impact genome variation at the intraspecific level. Here we assessed genome variation across four P. digitatum and seven P. expansum isolates from geographically distant regions. Our results show very high similarity (average 0.06 SNPs [single nucleotide polymorphism] per kb) between globally distributed isolates of P. digitatum pointing to a recent expansion of a single lineage. This low level of genetic variation found in our samples contrasts with the higher genetic variability observed in the similarly distributed P. expansum isolates (2.44 SNPs per kb). Patterns of polymorphism in P. expansum indicate that recombination exists between genetically diverged strains. Consistent with the existence of sexual recombination and heterothallism, which was unknown for this species, we identified the two alternative mating types in different P. expansum isolates. Patterns of polymorphism in P. digitatum indicate a recent clonal population expansion of a single lineage that has reached worldwide distribution. We suggest that the contrasting patterns of genomic variation between the two species reflect underlying differences in population dynamics related with host specificities and related agricultural practices. It should be noted, however, that this results should be confirmed with a larger sampling of strains, as new strains may broaden the diversity so far found in P. digitatum. PMID- 26672009 TI - Landscape genetics and population structure in Valley Oak (Quercus lobata Nee). AB - PREMISE OF THE STUDY: Although long-distance pollen movement is common in wind pollinated trees, barriers to gene flow may occur in species that have discontinuous ranges or are confined to certain habitat types. We investigated the genetic structure of Quercus lobata Nee populations throughout much of their range in California. We assessed the connectivity of populations and determined if barriers to gene flow occurred, and if so, if they corresponded to landscape features. METHODS: We collected leaf samples from 270 trees from 12 stands of Quercus lobata and genotyped these trees using eight polymorphic microsatellite loci. Genetic structure and clustering was evaluated using genetic distance methods, Bayesian clustering approaches, and network analysis of spatial genetic structure. KEY RESULTS: The southernmost population of Quercus lobata sampled from the Santa Monica area comprised a separate genetic cluster from the rest of the species, suggesting that Transverse Ranges such as the San Gabriel Mountains limit gene flow. Population differentiation among the other sites was small but significant. Network analysis reflected higher connectivity among populations along the Central Coast range, with few connections spanning the dry, low Central Valley. CONCLUSIONS: While long distance pollen movement has been shown to be common in oaks, on larger spatial scales, topographic features such as mountain ranges and the large, flat Central Valley of California limit gene flow. Such landscape features explain gene flow patterns much better than geographic distance alone. PMID- 26672010 TI - The influence of herbivory on pre- and postzygotic stages of reproduction following open, self, and outcross pollination. AB - PREMISE OF THE STUDY: Herbivory affects pollination success and reproductive output in plants. However, the different stages in the process from pollination to seed maturation have hardly been investigated within the context of herbivory. Herbivory might affect these stages via its effect on geitonogamous pollination and thereby the proportion of self pollen delivered to the stigma and/or via its effect on the nutritional capacity of the maternal plant. METHODS: Plants of monocarpic Cynoglossum officinale were experimentally subjected to root herbivory and exposed to natural open pollination in combination with self and outcross hand pollination. We quantified pollen germination, pollen tube competition intensity, pollen tube attrition, fruit set, and seed initiation, abortion, and maturation. KEY RESULTS: Although root herbivory did not affect pollen germination or pollen tube attrition, fruit set and seed initiation and maturation were negatively affected by herbivory, but for seed initiation only in the case of outcross- and open-pollinated flowers. The intensity of pollen tube competition positively affected seed initiation, but only in plants infested with the herbivore. CONCLUSIONS: Our study demonstrates that herbivory did not affect the early stages following pollination, but significantly impacted later postpollination stages such as fruit set and seed maturation and selection based on pollen tube competition intensity on zygote development. Our findings suggest that decreased nutritional capacity of the mother plant in response to root herbivory rather than herbivory effects on pollen quality was responsible for the lower fruit and seed production in infested plants. PMID- 26672012 TI - Arctic plant responses to changing abiotic factors in northern Alaska. AB - PREMISE OF THE STUDY: Understanding the relationship between plants and changing abiotic factors is necessary to document and anticipate the impacts of climate change. METHODS: We used data from long-term research sites at Barrow and Atqasuk, Alaska, to investigate trends in abiotic factors (snow melt and freeze up dates, air and soil temperature, thaw depth, and soil moisture) and their relationships with plant traits (inflorescence height, leaf length, reproductive effort, and reproductive phenology) over time. KEY RESULTS: Several abiotic factors, including increasing air and soil temperatures, earlier snowmelt, delayed freeze-up, drier soils, and increasing thaw depths, showed nonsignificant tendencies over time that were consistent with the regional warming pattern observed in the Barrow area. Over the same period, plants showed consistent, although typically nonsignificant tendencies toward increasing inflorescence heights and reproductive efforts. Air and soil temperatures, measured as degree days, were consistently correlated with plant growth and reproductive effort. Reproductive effort was best predicted using abiotic conditions from the previous year. We also found that varying the base temperature used to calculate degree days changed the number of significant relationships between temperature and the trait: in general, reproductive phenologies in colder sites were better predicted using lower base temperatures, but the opposite held for those in warmer sites. CONCLUSIONS: Plant response to changing abiotic factors is complex and varies by species, site, and trait; however, for six plant species, we have strong evidence that climate change will cause significant shifts in their growth and reproductive effort as the region continues to warm. PMID- 26672013 TI - Multi-gene phylogeny of the genus Lobaria: Evidence of species-pair and allopatric cryptic speciation in East Asia. AB - PREMISE OF THE STUDY: Accurate species delimitation has critical implications for ecological and conservation studies. The lichen genus Lobaria is widely distributed in old-growth forests. Particularly in East Asia, this genus includes many rare and poorly known taxa that are circumscribed as morpho- or chemospecies, as well as species-pairs. METHODS: To critically examine the relationships between species identified via morphological and chemical criteria, phylogenetic species recognition (PSR) was applied to the genus Lobaria. Morphological and chemical patterns of 87 individuals were examined and three independent nuclear loci were sequenced. The East Asian L. meridionalis-group was additionally studied using split decomposition and haplotype network analysis. KEY RESULTS: The genus Lobaria and most of its species were strongly supported statistically. Split decomposition and haplotype networks suggest complex evolutionary histories of species within the East Asian L. meridionalis-group. CONCLUSIONS: Phylogenetic analyses confirmed the monophyly of the genus Lobaria, including L. anomala. Within Lobaria, three major clades were found. These clades associate with different photobionts and comprise 18 known species and 5 undescribed species. Several chemical compounds were found to be neither stable nor invariant characters. Some taxa of the L. meridionalis-group appear to be monophyletic but remain as allopatric cryptic species. In three clades, this study found evidence for diversification processes between isidiate and nonisidiate specimens (species-pair). These findings are discussed in the context of evolutionary hypotheses for speciation processes. PMID- 26672015 TI - Decoding the stem cell quiescence cycle--lessons from yeast for regenerative biology. AB - In the past decade, major advances have occurred in the understanding of mammalian stem cell biology, but roadblocks (including gaps in our fundamental understanding) remain in translating this knowledge to regenerative medicine. Interestingly, a close analysis of the Saccharomyces cerevisiae literature leads to an appreciation of how much yeast biology has contributed to the conceptual framework underpinning our understanding of stem cell behavior, to the point where such insights have been internalized into the realm of the known. This Opinion article focuses on one such example, the quiescent adult mammalian stem cell, and examines concepts underlying our understanding of quiescence that can be attributed to studies in yeast. We discuss the metabolic, signaling and gene regulatory events that control entry and exit into quiescence in yeast. These processes and events retain remarkable conservation and conceptual parallels in mammalian systems, and collectively suggest a regulated program beyond the cessation of cell division. We argue that studies in yeast will continue to not only reveal fundamental concepts in quiescence, but also leaven progress in regenerative medicine. PMID- 26672017 TI - The Association Between Alcohol Consumption and Lung Carcinoma by Histological Subtype. AB - Alcohol is a carcinogen suspected of increasing lung cancer risk. Therefore, we prospectively evaluated the relationship between alcohol consumption and lung carcinoma in 492,902 persons from the National Institutes of Health-AARP Diet and Health Study. We used Cox models to calculate hazard ratios and 95% confidence intervals, adjusting for tobacco smoking and other potential confounders. Between 1995/1996 and December 31, 2006, there were 10,227 incident cases of lung carcinoma, classified as adenocarcinoma (n = 4,036), squamous cell carcinoma (n = 1,998), small cell carcinoma (n = 1,524), undifferentiated carcinoma (n = 559), and other (n = 2,110). Compared with nondrinking, alcohol consumption was associated with a modest nonlinear reduction in total lung carcinoma risk at lower levels of consumption (for 0.5-<1 drink/day, HR = 0.89, 95% confidence interval: 0.82, 0.96) but a modest increase in risk in the highest category (for >=7 drinks/day, HR = 1.11, 95% confidence interval: 1.00, 1.24). Regarding histological type, alcohol was associated with a nonlinear reduction in squamous cell carcinoma that became attenuated as consumption increased and a modest increase in adenocarcinoma among heavier drinkers. Cubic spline models confirmed these findings. Our data suggest that the relationship between alcohol consumption and lung carcinoma differs by histological subtype. PMID- 26672018 TI - Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland. AB - The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance. PMID- 26672019 TI - DNA methylation changes induced by long and short photoperiods in Nasonia. AB - Many organisms monitor the annual change in day length and use this information for the timing of their seasonal response. However, the molecular mechanisms underlying photoperiodic timing are largely unknown. The wasp Nasonia vitripennis is an emerging model organism that exhibits a strong photoperiodic response: Short autumnal days experienced by females lead to the induction of developmental arrest (diapause) in their progeny, allowing winter survival of the larvae. How female Nasonia control the developmental trajectory of their offspring is unclear. Here, we took advantage of the recent discovery that DNA methylation is pervasive in Nasonia and tested its role in photoperiodism. We used reduced representation bisulfite sequencing (RRBS) to profile DNA methylation in adult female wasps subjected to different photoperiods and identified substantial differential methylation at the single base level. We also show that knocking down DNA methyltransferase 1a (Dnmt1a), Dnmt3, or blocking DNA methylation pharmacologically, largely disrupts the photoperiodic diapause response of the wasps. To our knowledge, this is the first example for a role of DNA methylation in insect photoperiodic timing. PMID- 26672020 TI - New Estimates of the Sandwich Generation in the 2013 Panel Study of Income Dynamics. AB - Purpose of the Study: We use the Roster and Transfers Module in the 2013 Panel Study of Income Dynamics to obtain the first estimates of the prevalence of transfers to adult children and parents for United States men and women aged 35 75. Design and Methods: This article extends the current understanding of the sandwich generation by comparing recent transfers of time and money to parents and adult children for men and women and across ages between 35 and 75 years of age. Results: Over 30% of individuals with living parents and adult children provide transfers to two generations. The prevalence of transfers does not differ by age and the differences between men and women are small, though statistically significant. Conditional on providing time transfers, women provide more hours of help than men, particularly to their adult children. The number of hours given to children exceeds the number given to parents. Implications: These findings are the first to show that both men and women are likely to provide transfers to two generations and that transfers to two generations are common across adult ages. Our findings suggest a need to rethink the notion of the sandwich generation, which has focused on women in late middle age, to include men and women across younger and older ages. PMID- 26672021 TI - Global Challenges in Retinopathy of Prematurity Screening: Modern Solutions for Modern Times. PMID- 26672023 TI - Patent Ductus Arteriosus in Preterm Infants. AB - Despite a large body of basic science and clinical research and clinical experience with thousands of infants over nearly 6 decades,(1) there is still uncertainty and controversy about the significance, evaluation, and management of patent ductus arteriosus in preterm infants, resulting in substantial heterogeneity in clinical practice. The purpose of this clinical report is to summarize the evidence available to guide evaluation and treatment of preterm infants with prolonged ductal patency in the first few weeks after birth. PMID- 26672024 TI - Return-to-Sport Outcomes After Revision Anterior Cruciate Ligament Reconstruction Surgery. AB - BACKGROUND: There are limited and inconsistent data regarding return-to-sport outcomes after revision anterior cruciate ligament reconstruction (ACLR). HYPOTHESIS: Return-to-sport rates will be lower after revision ACLR when compared with primary ACLR. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study cohort consisted of 136 eligible patients who had undergone their first revision ACLR between March 2006 and March 2010. Of these, 109 patients (80%) completed a sports activity survey at a mean 5-year follow-up (range, 3-7 years). Follow-up also included the International Knee Documentation Committee (IKDC) subjective form, Marx Activity Scale, and Knee injury and Osteoarthritis Outcome Score-quality of life (KOOS-QOL) form. Operative details were obtained from the clinical record. RESULTS: After revision ACLR, 46% (95% CI, 37%-55%) of patients returned to their preinjury level of sport, compared with 50% (95% CI, 41%-59%) after the primary reconstruction in the same patients. Of the patients who were not able to return to their preinjury level of sport after primary reconstruction, 33% improved to the point that they were able to do so after revision. Younger patients were more likely to have returned to their same level of sport (58% vs 38%, P < .05), while the rate of return was the same between male and female patients. Those who returned to their preinjury level of sport scored higher Marx (P < .01), KOOS-QOL (P < .001), and IKDC scores (P < .01) than those who did not. Patients with <50% thickness articular cartilage lesions at revision surgery were more likely to have returned to their preinjury level (52% vs 31%, P < .05) and had significantly better Marx (P < .01), KOOS-QOL (P < .01), and IKDC scores (P < .01) at follow-up. The status of the menisci at the time of revision surgery was not associated with rates of return to sport, but patients with an intact medial meniscus had significantly higher KOOS-QOL (P < .05) scores at follow-up. CONCLUSION: Return-to-sport rates of patients after revision ACLR were similar to those after their primary surgery but were still lower than the reported rates of ACLR patients who did not need revision surgery. Greater chondral pathologic abnormalities at revision surgery were associated with reduced function at follow-up. PMID- 26672022 TI - A Comparison of Strategies for Retinopathy of Prematurity Detection. AB - BACKGROUND AND OBJECTIVES: Delayed detection of type 1 retinopathy of prematurity (ROP) can lead to permanent visual impairment. Providing ROP examinations is challenging because of the limited ophthalmology workforce. This study compares digital imaging-based ROP detection strategies versus serial ROP examinations. METHODS: We conducted an individual-level microsimulation study of a hypothetical cohort of 650 infants with gestational age from 23 to 30 weeks. Infants were evaluated by using strategies based on indirect ophthalmoscopy or digital imaging beginning at 32 weeks' postmenstrual age (PMA) and continuing to discharge, transfer, or 40 weeks' PMA. ROP status and the accuracy of digital imaging were based on the e-ROP (Telemedicine Approaches to Evaluating Acute-Phase ROP) study, which enrolled high-risk infants. RESULTS: Within the hypothetical NICU, the strategy of ROP examinations identified an average of 45.8 cases of type 1 ROP by discharge, transfer, or 40 weeks' PMA, and another 1.9 cases were included in the group of infants recommended to have later follow-up. Digital imaging with an ROP examination at discharge identified all 47.7 cases of type 1 ROP. On average, the ROP examination-only strategy required 1745.7 ROP examinations, whereas digital imaging with a discharge examination required 1065.5 ROP examinations and 1786.2 digital imaging sessions. CONCLUSIONS: Although digital imaging decreased the number of ROP examinations per infant, there was an increase in the total number of interventions (ie, ROP examinations and imaging sessions). Providing an ROP examination at the time of NICU discharge can significantly reduce the number of infants who require follow-up. PMID- 26672025 TI - Determinants of Return to Play After the Nonoperative Management of Hamstring Injuries in Athletes: A Systematic Review. AB - BACKGROUND: It is important for clinicians to rely on suitable prognosis factors after hamstring injuries because of the high incidence of these injuries and time away from athletic activities. PURPOSE: To summarize the current literature on factors that influence return to play after a hamstring injury in athletes. STUDY DESIGN: Systematic review. METHODS: A computer-assisted literature search of CINAHL, MEDLINE, Embase, and EBM Reviews databases (and a manual search of the reference lists of all selected articles) was conducted using keywords related to hamstring injuries and return to play. The literature review criteria included (1) patients with an acute hamstring or posterior thigh injury; (2) a randomized controlled trial, cohort study, case-control study, case series, or prospective or retrospective design; (3) information on rehabilitation, physical therapy, clinical assessment, imaging techniques, and return to play; and (4) studies written in English or French. RESULTS: The search strategy identified 914 potential articles, of which 24 met the inclusion criteria. In terms of the clinical assessment, the following factors were associated with a longer recovery time: stretching-type injuries, recreational-level sports, structural versus functional injuries, greater range of motion deficit with the hip flexed at 90 degrees , time to first consultation >1 week, increased pain on the visual analog scale, and >1 day to be able to walk pain free after the injury. As for magnetic resonance imaging studies, the following factors correlated with a longer recovery time: positive findings; higher grade of injury; muscle involvement >75%; complete transection; retraction; central tendon disruption of the biceps femoris; proximal tendon involvement; shorter distance to the ischial tuberosity; length of the hamstring injury; and depth, volume, and large cross-sectional area. With respect to ultrasound studies, the following factors were associated with a poor prognosis: large cross-sectional area, injury outside the musculotendinous junction, hematoma, structural injury, and injury involving the biceps femoris. Lastly, rehabilitation approaches that included hamstring loading during extensive lengthening or 4 daily sessions of static hamstring stretching led to shorter rehabilitation times. CONCLUSION: Numerous determinants have an effect on return to play after a hamstring injury in athletes. It is important for sports professionals to be aware of those determinants to guide athletes through the rehabilitation process and refine return-to-play strategies. PMID- 26672026 TI - Sex-Based Differences as a Predictor of Recovery Trajectories in Young Athletes After a Sports-Related Concussion. AB - BACKGROUND: To date, few studies have delineated clear sex-based differences in symptom resolution after a sports-related concussion (SRC), and equivocal results have been identified in sex-based differences on baseline assessments. PURPOSE: To assess whether female athletes displayed prolonged recovery and more symptoms at baseline and after an SRC compared with male athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The current study assessed 135 male and 41 female athletes (10-18 years old) who participated in high-impact sports in metropolitan Atlanta middle and high schools. All athletes completed a baseline assessment and at least 1 postconcussion assessment from the Immediate Post Concussion Assessment and Cognitive Testing battery. Longitudinal hierarchical linear modeling was employed to examine individual-level variables and their associations with adolescents' rates of recovery in concussive symptoms after controlling for age and number of prior concussions. RESULTS: Aggregate symptoms were rated as higher in female athletes compared with male athletes at baseline (mean +/- SD: females, 13.49 +/- 11.20; males, 4.88 +/- 8.74; F(1,175) = 10.59, P < .001) and immediately after a concussion (females: 16.75 +/- 18.08; males: 10.58 +/- 14.21; F(1,175) = 3.99, P = .05). There were no group differences in the slope of recovery between male and female athletes, indicating generally similar trajectories of change for both groups. Post hoc analyses revealed higher baseline levels of migraine and neuropsychological symptoms in female athletes. CONCLUSION: Although female athletes in the current study reported increased symptoms, identical recovery patterns were observed in both sexes, suggesting that sex-based differences in concussion recovery are better explained by increased symptom frequency among female athletes when compared with their male counterparts. PMID- 26672027 TI - Pharmacology of Heparin and Related Drugs. AB - Heparin has been recognized as a valuable anticoagulant and antithrombotic for several decades and is still widely used in clinical practice for a variety of indications. The anticoagulant activity of heparin is mainly attributable to the action of a specific pentasaccharide sequence that acts in concert with antithrombin, a plasma coagulation factor inhibitor. This observation has led to the development of synthetic heparin mimetics for clinical use. However, it is increasingly recognized that heparin has many other pharmacological properties, including but not limited to antiviral, anti-inflammatory, and antimetastatic actions. Many of these activities are independent of its anticoagulant activity, although the mechanisms of these other activities are currently less well defined. Nonetheless, heparin is being exploited for clinical uses beyond anticoagulation and developed for a wide range of clinical disorders. This article provides a "state of the art" review of our current understanding of the pharmacology of heparin and related drugs and an overview of the status of development of such drugs. PMID- 26672028 TI - Simultaneous CT-MRI Reconstruction for Constrained Imaging Geometries Using Structural Coupling and Compressive Sensing. AB - OBJECTIVE: A unified reconstruction framework is presented for simultaneous CT MRI reconstruction. METHODS: In an ideal CT-MRI scanner, CT and MRI acquisitions would occur simultaneously, and would be inherently registered in space and time. Alternatively, separately acquired CT and MRI scans can be fused to simulate an instantaneous acquisition. In this study, structural coupling and compressive sensing techniques are combined to unify CT and MRI reconstructions. A bidirectional image estimation method was proposed to connect images from different modalities. Hence, CT and MRI data serve as prior knowledge to each other for better CT and MRI image reconstruction than what could be achieved with separate reconstruction. SIGNIFICANCE: Combined CT-MRI imaging has the potential for improved results in existing preclinical and clinical applications, as well as opening novel research directions for future applications. RESULTS: Our integrated reconstruction methodology is demonstrated with numerical phantom and real-dataset-based experiments, and has yielded promising results. PMID- 26672029 TI - An Unsorted Spike-Based Pattern Recognition Method for Real-Time Continuous Sensory Event Detection from Dorsal Root Ganglion Recording. AB - In functional neuromuscular stimulation systems, sensory information-based closed loop control can be useful for restoring lost function in patients with hemiplegia or quadriplegia. The goal of this study was to detect sensory events from tactile afferent signals continuously in real time using a novel unsorted spike-based pattern recognition method. The tactile afferent signals were recorded with a 16-channel microelectrode in the dorsal root ganglion, and unsorted spike-based feature vectors were extracted as a novel combination of the time and time-frequency domain features. Principal component analysis was used to reduce the dimensionality of the feature vectors, and a multilayer perceptron classifier was used to detect sensory events. The proposed method showed good performance for classification accuracy, and the processing time delay of sensory event detection was less than 200 ms. These results indicated that the proposed method could be applicable for sensory feedback in closed-loop control systems. PMID- 26672030 TI - An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study. AB - OBJECTIVE: Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally. METHOD: The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging. RESULT: The system successfully obtained high resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 MUm diameter. CONCLUSION: For the first time, high resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques. PMID- 26672031 TI - Machine Learning Methods for Binary and Multiclass Classification of Melanoma Thickness From Dermoscopic Images. AB - Thickness of the melanoma is the most important factor associated with survival in patients with melanoma. It is most commonly reported as a measurement of depth given in millimeters (mm) and computed by means of pathological examination after a biopsy of the suspected lesion. In order to avoid the use of an invasive method in the estimation of the thickness of melanoma before surgery, we propose a computational image analysis system from dermoscopic images. The proposed feature extraction is based on the clinical findings that correlate certain characteristics present in dermoscopic images and tumor depth. Two supervised classification schemes are proposed: a binary classification in which melanomas are classified into thin or thick, and a three-class scheme (thin, intermediate, and thick). The performance of several nominal classification methods, including a recent interpretable method combining logistic regression with artificial neural networks (Logistic regression using Initial variables and Product Units, LIPU), is compared. For the three-class problem, a set of ordinal classification methods (considering ordering relation between the three classes) is included. For the binary case, LIPU outperforms all the other methods with an accuracy of 77.6%, while, for the second scheme, although LIPU reports the highest overall accuracy, the ordinal classification methods achieve a better balance between the performances of all classes. PMID- 26672032 TI - Non-Parametric Bayesian Registration (NParBR) of Body Tumors in DCE-MRI Data. AB - The identification of tumors in the internal organs of chest, abdomen, and pelvis anatomic regions can be performed with the analysis of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) data. The contrast agent is accumulated differently by pathologic and healthy tissues and that results in a temporally varying contrast in an image series. The internal organs are also subject to potentially extensive movements mainly due to breathing, heart beat, and peristalsis. This contributes to making the analysis of DCE-MRI datasets challenging as well as time consuming. To address this problem we propose a novel pairwise non-rigid registration method with a Non-Parametric Bayesian Registration (NParBR) formulation. The NParBR method uses a Bayesian formulation that assumes a model for the effect of the distortion on the joint intensity statistics, a non-parametric prior for the restored statistics, and also applies a spatial regularization for the estimated registration with Gaussian filtering. A minimally biased intra-dataset atlas is computed for each dataset and used as reference for the registration of the time series. The time series registration method has been tested with 20 datasets of liver, lungs, intestines, and prostate. It has been compared to the B-Splines and to the SyN methods with results that demonstrate that the proposed method improves both accuracy and efficiency. PMID- 26672033 TI - Human Visual System-Based Fundus Image Quality Assessment of Portable Fundus Camera Photographs. AB - Telemedicine and the medical "big data" era in ophthalmology highlight the use of non-mydriatic ocular fundus photography, which has given rise to indispensable applications of portable fundus cameras. However, in the case of portable fundus photography, non-mydriatic image quality is more vulnerable to distortions, such as uneven illumination, color distortion, blur, and low contrast. Such distortions are called generic quality distortions. This paper proposes an algorithm capable of selecting images of fair generic quality that would be especially useful to assist inexperienced individuals in collecting meaningful and interpretable data with consistency. The algorithm is based on three characteristics of the human visual system--multi-channel sensation, just noticeable blur, and the contrast sensitivity function to detect illumination and color distortion, blur, and low contrast distortion, respectively. A total of 536 retinal images, 280 from proprietary databases and 256 from public databases, were graded independently by one senior and two junior ophthalmologists, such that three partial measures of quality and generic overall quality were classified into two categories. Binary classification was implemented by the support vector machine and the decision tree, and receiver operating characteristic (ROC) curves were obtained and plotted to analyze the performance of the proposed algorithm. The experimental results revealed that the generic overall quality classification achieved a sensitivity of 87.45% at a specificity of 91.66%, with an area under the ROC curve of 0.9452, indicating the value of applying the algorithm, which is based on the human vision system, to assess the image quality of non-mydriatic photography, especially for low-cost ophthalmological telemedicine applications. PMID- 26672035 TI - Simulations of the Hadamard Variance: Probability Distributions and Confidence Intervals. AB - Power-law noise in clocks and oscillators can be simulated by Fourier transforming a modified spectrum of white phase noise. This approach has been applied successfully to simulation of the Allan variance and the modified Allan variance in both overlapping and nonoverlapping forms. When significant frequency drift is present in an oscillator, at large sampling times the Allan variance overestimates the intrinsic noise, while the Hadamard variance is insensitive to frequency drift. The simulation method is extended in this paper to predict the Hadamard variance for the common types of power-law noise. Symmetric real matrices are introduced whose traces-the sums of their eigenvalues-are equal to the Hadamard variances, in overlapping or nonoverlapping forms, as well as for the corresponding forms of the modified Hadamard variance. We show that the standard relations between spectral densities and Hadamard variance are obtained with this method. The matrix eigenvalues determine probability distributions for observing a variance at an arbitrary value of the sampling interval tau, and hence for estimating confidence in the measurements. PMID- 26672036 TI - Stereoscopic 3D Visual Discomfort Prediction: A Dynamic Accommodation and Vergence Interaction Model. AB - The human visual system perceives 3D depth following sensing via its binocular optical system, a series of massively parallel processing units, and a feedback system that controls the mechanical dynamics of eye movements and the crystalline lens. The process of accommodation (focusing of the crystalline lens) and binocular vergence is controlled simultaneously and symbiotically via cross coupled communication between the two critical depth computation modalities. The output responses of these two subsystems, which are induced by oculomotor control, are used in the computation of a clear and stable cyclopean 3D image from the input stimuli. These subsystems operate in smooth synchronicity when one is viewing the natural world; however, conflicting responses can occur when viewing stereoscopic 3D (S3D) content on fixed displays, causing physiological discomfort. If such occurrences could be predicted, then they might also be avoided (by modifying the acquisition process) or ameliorated (by changing the relative scene depth). Toward this end, we have developed a dynamic accommodation and vergence interaction (DAVI) model that successfully predicts visual discomfort on S3D images. The DAVI model is based on the phasic and reflex responses of the fast fusional vergence mechanism. Quantitative models of accommodation and vergence mismatches are used to conduct visual discomfort prediction. Other 3D perceptual elements are included in the proposed method, including sharpness limits imposed by the depth of focus and fusion limits implied by Panum's fusional area. The DAVI predictor is created by training a support vector machine on features derived from the proposed model and on recorded subjective assessment results. The experimental results are shown to produce accurate predictions of experienced visual discomfort. PMID- 26672034 TI - Dual Orientation 16-MHz Single-Element Ultrasound Needle Transducers for Image Guided Neurosurgical Intervention. AB - Image-guided surgery is today considered to be of significant importance in neurosurgical applications. However, one of its major shortcomings is its reliance on preoperative image data, which does not account for brain deformations and displacements that occur during surgery. In this work, we propose to tackle this issue through the incorporation of an ultrasound device within the type of biopsy needles commonly used as an interventional tool to provide immediate feedback to neurosurgeons during surgical procedures. To identify the most appropriate path to access a targeted tissue site, single element transducers that look either forward or sideways have been designed and fabricated. Micromolded 1-3 piezocomposites were adopted as the active materials for feasibility tests and epoxy lenses have been applied to focus the ultrasound beam. Electrical impedance analysis, pulse-echo testing, and wire phantom scanning have been carried out, demonstrating the functionality of the needle transducers at [Formula: see text]. The capabilities of these transducers for intraoperative image guidance were demonstrated by imaging within soft-embalmed cadaveric human brain and fresh porcine brain. PMID- 26672037 TI - Detail-Preserving and Content-Aware Variational Multi-View Stereo Reconstruction. AB - Accurate recovery of 3D geometrical surfaces from calibrated 2D multi-view images is a fundamental yet active research area in computer vision. Despite the steady progress in multi-view stereo (MVS) reconstruction, many existing methods are still limited in recovering fine-scale details and sharp features while suppressing noises, and may fail in reconstructing regions with less textures. To address these limitations, this paper presents a detail-preserving and content aware variational (DCV) MVS method, which reconstructs the 3D surface by alternating between reprojection error minimization and mesh denoising. In reprojection error minimization, we propose a novel inter-image similarity measure, which is effective to preserve fine-scale details of the reconstructed surface and builds a connection between guided image filtering and image registration. In mesh denoising, we propose a content-aware lp-minimization algorithm by adaptively estimating the p value and regularization parameters. Compared with conventional isotropic mesh smoothing approaches, the proposed method is much more promising in suppressing noise while preserving sharp features. Experimental results on benchmark data sets demonstrate that our DCV method is capable of recovering more surface details, and obtains cleaner and more accurate reconstructions than the state-of-the-art methods. In particular, our method achieves the best results among all published methods on the Middlebury dino ring and dino sparse data sets in terms of both completeness and accuracy. PMID- 26672038 TI - Learning of Multimodal Representations With Random Walks on the Click Graph. AB - In multimedia information retrieval, most classic approaches tend to represent different modalities of media in the same feature space. With the click data collected from the users' searching behavior, existing approaches take either one to-one paired data (text-image pairs) or ranking examples (text-query-image and/or image-query-text ranking lists) as training examples, which do not make full use of the click data, particularly the implicit connections among the data objects. In this paper, we treat the click data as a large click graph, in which vertices are images/text queries and edges indicate the clicks between an image and a query. We consider learning a multimodal representation from the perspective of encoding the explicit/implicit relevance relationship between the vertices in the click graph. By minimizing both the truncated random walk loss as well as the distance between the learned representation of vertices and their corresponding deep neural network output, the proposed model which is named multimodal random walk neural network (MRW-NN) can be applied to not only learn robust representation of the existing multimodal data in the click graph, but also deal with the unseen queries and images to support cross-modal retrieval. We evaluate the latent representation learned by MRW-NN on a public large-scale click log data set Clickture and further show that MRW-NN achieves much better cross-modal retrieval performance on the unseen queries/images than the other state-of-the-art methods. PMID- 26672039 TI - Super-Interpolation With Edge-Orientation-Based Mapping Kernels for Low Complex 2* Upscaling. AB - With the advent of ultrahigh-definition (UHD) video services, super-resolution (SR) techniques are often required to generate high-resolution (HR) images from low-resolution (LR) images, such as HD images. To generate such HR images and a video of UHD resolutions in limited computing devices with hardware and software, low complex but excellent SR methods are particularly required. In this paper, we present a novel and fast SR method, called super-interpolation (SI), by unifying an interpolation step and a quality-enhancement step. The proposed SI method utilizes edge-orientation (EO)-based pre-learned kernels, which inherits the simplicity of interpolation and the quality enhancement of SR. It performs SR directly from the initial resolution of an input image to the target resolution of an up-scaled output image without requiring any intermediate interpolated image. The proposed SI method involves offline training and online up-scaling phases. In the offline training phase, training LR image patches are clustered based on their edge orientations into different EO classes for which class dependent linear mapping functions are learned between training LR and HR image patches. In up-scaling phase, an HR output image patch for each LR input image patch is generated by applying an appropriate linear mapping function selected based on the EO of LR input image patch. Our proposed SI method is intensively compared with the ten state-of-the-art SR methods for common image sets and many HD/UHD images. The experimental results show that the SI method yields the smallest running time and requires relatively small hardware resources. It outperforms the six state-of-the-art methods in average (peak signal-to-noise ratio) PSNR/(structural similarity) SSIM, and exhibits competitive or somewhat lower PSNR/SSIM performance compared with the others. PMID- 26672040 TI - Bayesian Depth-From-Defocus With Shading Constraints. AB - We present a method that enhances the performance of depth-from-defocus (DFD) through the use of shading information. DFD suffers from important limitations- namely coarse shape reconstruction and poor accuracy on textureless surfaces- that can be overcome with the help of shading. We integrate both forms of data within a Bayesian framework that capitalizes on their relative strengths. Shading data, however, is challenging to accurately recover from surfaces that contain texture. To address this issue, we propose an iterative technique that utilizes depth information to improve shading estimation, which in turn is used to elevate depth estimation in the presence of textures. The shading estimation can be performed in general scenes with unknown illumination using an approximate estimate of scene lighting. With this approach, we demonstrate improvements over existing DFD techniques, as well as effective shape reconstruction of textureless surfaces. PMID- 26672041 TI - Quaternionic Local Ranking Binary Pattern: A Local Descriptor of Color Images. AB - This paper proposes a local descriptor called quaternionic local ranking binary pattern (QLRBP) for color images. Different from traditional descriptors that are extracted from each color channel separately or from vector representations, QLRBP works on the quaternionic representation (QR) of the color image that encodes a color pixel using a quaternion. QLRBP is able to handle all color channels directly in the quaternionic domain and include their relations simultaneously. Applying a Clifford translation to QR of the color image, QLRBP uses a reference quaternion to rank QRs of two color pixels, and performs a local binary coding on the phase of the transformed result to generate local descriptors of the color image. Experiments demonstrate that the QLRBP outperforms several state-of-the-art methods. PMID- 26672042 TI - Articulated and Generalized Gaussian Kernel Correlation for Human Pose Estimation. AB - In this paper, we propose an articulated and generalized Gaussian kernel correlation (GKC)-based framework for human pose estimation. We first derive a unified GKC representation that generalizes the previous sum of Gaussians (SoG) based methods for the similarity measure between a template and an observation both of which are represented by various SoG variants. Then, we develop an articulated GKC (AGKC) by integrating a kinematic skeleton in a multivariate SoG template that supports subject-specific shape modeling and articulated pose estimation for both the full body and the hands. We further propose a sequential (body/hand) pose tracking algorithm by incorporating three regularization terms in the AGKC function, including visibility, intersection penalty, and pose continuity. Our tracking algorithm is simple yet effective and computationally efficient. We evaluate our algorithm on two benchmark depth data sets. The experimental results are promising and competitive when compared with the state of-the-art algorithms. PMID- 26672045 TI - Relative Scale Estimation and 3D Registration of Multi-Modal Geometry Using Growing Least Squares. AB - The advent of low cost scanning devices and the improvement of multi-view stereo techniques have made the acquisition of 3D geometry ubiquitous. Data gathered from different devices, however, result in large variations in detail, scale, and coverage. Registration of such data is essential before visualizing, comparing and archiving them. However, state-of-the-art methods for geometry registration cannot be directly applied due to intrinsic differences between the models, e.g., sampling, scale, noise. In this paper we present a method for the automatic registration of multi-modal geometric data, i.e., acquired by devices with different properties (e.g., resolution, noise, data scaling). The method uses a descriptor based on Growing Least Squares, and is robust to noise, variation in sampling density, details, and enables scale-invariant matching. It allows not only the measurement of the similarity between the geometry surrounding two points, but also the estimation of their relative scale. As it is computed locally, it can be used to analyze large point clouds composed of millions of points. We implemented our approach in two registration procedures (assisted and automatic) and applied them successfully on a number of synthetic and real cases. We show that using our method, multi-modal models can be automatically registered, regardless of their differences in noise, detail, scale, and unknown relative coverage. PMID- 26672044 TI - Thyroid hormone receptor-alpha deletion decreases heart function and exercise performance in apolipoprotein E-deficient mice. AB - The deletion of thyroid hormone receptor-alpha (TRalpha) in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice (ApoE(-/-)TRalpha(0/0)) accelerates the formation of atherosclerotic plaques without aggravation of hypercholesterolemia. To evaluate other predisposition risk factors to atherosclerosis in this model, we studied blood pressure (BP) and cardiac and vascular functions, as well as exercise tolerance in young adult ApoE(-/ )TRalpha(0/0) mice before the development of atherosclerotic plaques. Telemetric BP recorded for 4 consecutive days showed that the spontaneous systolic BP was slightly decreased in ApoE(-/-)TRalpha(0/0) compared with ApoE(-/-) mice associated with a reduced locomotor activity. The percentage of animals that completed endurance (57% vs. 89%) and maximal running (0% vs. 89% at 46 cm/s speed in ApoE(-/-)TRalpha(0/0) and ApoE(-/-) mice, respectively) tests was lower in ApoE(-/-)TRalpha(0/0) mice. Moreover, during the maximal running test, both maximal running speed and running distance were significantly reduced in ApoE(-/ )TRalpha(0/0) mice, associated with a blunted BP response to exercise. Transthoracic echocardiography revealed a decreased interventricular septum thickness and an increased end-systolic left ventricular volume in ApoE(-/ )TRalpha(0/0) mice. Accordingly, left ventricular fractional shortening, ejection fraction, and stroke volume were all significantly decreased in ApoE(-/ )TRalpha(0/0) mice with a concomitant blunted cardiac output. No interstrain difference was observed in vascular reactivity, except that ApoE(-/-)TRalpha(0/0) mice exhibited an enhanced acetylcholine-induced relaxation in mesenteric and distal femoral arteries. In conclusion, the deletion of TRalpha in ApoE(-/-) mice alters cardiac structure and contractility; both could contribute to blunted BP response to physical exercise and impaired exercise performance. PMID- 26672043 TI - Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue. AB - Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro. PMID- 26672046 TI - Towards Extracting Supporting Information About Predicted Protein-Protein Interactions. AB - One of the goals of relation extraction is to identify protein-protein interactions (PPIs) in biomedical literature. Current systems are capturing binary relations and also the direction and type of an interaction. Besides assisting in the curation PPIs into databases, there has been little real-world application of these algorithms. We describe UPSITE, a text mining tool for extracting evidence in support of a hypothesized interaction. Given a predicted PPI, UPSITE uses a binary relation detector to check whether a PPI is found in abstracts in PubMed. If it is not found, UPSITE retrieves documents relevant to each of the two proteins separately, and extracts contextual information about biological events surrounding each protein, and calculates semantic similarity of the two proteins to provide evidential support for the predicted PPI. In evaluations, relation extraction achieved an Fscore of 0.88 on the HPRD50 corpus, and semantic similarity measured with angular distance was found to be statistically significant. With the development of PPI prediction algorithms, the burden of interpreting the validity and relevance of novel PPIs is on biologists. We suggest that presenting annotations of the two proteins in a PPI side-by-side and a score that quantifies their similarity lessens this burden to some extent. PMID- 26672047 TI - Characteristic Gene Selection Based on Robust Graph Regularized Non-Negative Matrix Factorization. AB - Many methods have been considered for gene selection and analysis of gene expression data. Nonetheless, there still exists the considerable space for improving the explicitness and reliability of gene selection. To this end, this paper proposes a novel method named robust graph regularized non-negative matrix factorization for characteristic gene selection using gene expression data, which mainly contains two aspects: Firstly, enforcing L21-norm minimization on error function which is robust to outliers and noises in data points. Secondly, it considers that the samples lie in low-dimensional manifold which embeds in a high dimensional ambient space, and reveals the data geometric structure embedded in the original data. To demonstrate the validity of the proposed method, we apply it to gene expression data sets involving various human normal and tumor tissue samples and the results demonstrate that the method is effective and feasible. PMID- 26672048 TI - A 128-Channel Extreme Learning Machine-Based Neural Decoder for Brain Machine Interfaces. AB - Currently, state-of-the-art motor intention decoding algorithms in brain-machine interfaces are mostly implemented on a PC and consume significant amount of power. A machine learning coprocessor in 0.35- MUm CMOS for the motor intention decoding in the brain-machine interfaces is presented in this paper. Using Extreme Learning Machine algorithm and low-power analog processing, it achieves an energy efficiency of 3.45 pJ/MAC at a classification rate of 50 Hz. The learning in second stage and corresponding digitally stored coefficients are used to increase robustness of the core analog processor. The chip is verified with neural data recorded in monkey finger movements experiment, achieving a decoding accuracy of 99.3% for movement type. The same coprocessor is also used to decode time of movement from asynchronous neural spikes. With time-delayed feature dimension enhancement, the classification accuracy can be increased by 5% with limited number of input channels. Further, a sparsity promoting training scheme enables reduction of number of programmable weights by ~ 2X. PMID- 26672049 TI - Why Deep Learning Works: A Manifold Disentanglement Perspective. AB - Deep hierarchical representations of the data have been found out to provide better informative features for several machine learning applications. In addition, multilayer neural networks surprisingly tend to achieve better performance when they are subject to an unsupervised pretraining. The booming of deep learning motivates researchers to identify the factors that contribute to its success. One possible reason identified is the flattening of manifold-shaped data in higher layers of neural networks. However, it is not clear how to measure the flattening of such manifold-shaped data and what amount of flattening a deep neural network can achieve. For the first time, this paper provides quantitative evidence to validate the flattening hypothesis. To achieve this, we propose a few quantities for measuring manifold entanglement under certain assumptions and conduct experiments with both synthetic and real-world data. Our experimental results validate the proposition and lead to new insights on deep learning. PMID- 26672050 TI - Unsupervised Metric Fusion Over Multiview Data by Graph Random Walk-Based Cross View Diffusion. AB - Learning an ideal metric is crucial to many tasks in computer vision. Diverse feature representations may combat this problem from different aspects; as visual data objects described by multiple features can be decomposed into multiple views, thus often provide complementary information. In this paper, we propose a cross-view fusion algorithm that leads to a similarity metric for multiview data by systematically fusing multiple similarity measures. Unlike existing paradigms, we focus on learning distance measure by exploiting a graph structure of data samples, where an input similarity matrix can be improved through a propagation of graph random walk. In particular, we construct multiple graphs with each one corresponding to an individual view, and a cross-view fusion approach based on graph random walk is presented to derive an optimal distance measure by fusing multiple metrics. Our method is scalable to a large amount of data by enforcing sparsity through an anchor graph representation. To adaptively control the effects of different views, we dynamically learn view-specific coefficients, which are leveraged into graph random walk to balance multiviews. However, such a strategy may lead to an over-smooth similarity metric where affinities between dissimilar samples may be enlarged by excessively conducting cross-view fusion. Thus, we figure out a heuristic approach to controlling the iteration number in the fusion process in order to avoid over smoothness. Extensive experiments conducted on real-world data sets validate the effectiveness and efficiency of our approach. PMID- 26672051 TI - Pull-Based Distributed Event-Triggered Consensus for Multiagent Systems With Directed Topologies. AB - This paper mainly investigates consensus problem with a pull-based event triggered feedback control. For each agent, the diffusion coupling feedbacks are based on the states of its in-neighbors at its latest triggering time, and the next triggering time of this agent is determined by its in-neighbors' information. The general directed topologies, including irreducible and reducible cases, are investigated. The scenario of distributed continuous communication is considered first. It is proved that if the network topology has a spanning tree, then the event-triggered coupling algorithm can realize the consensus for the multiagent system. Then, the results are extended to discontinuous communication, i.e., self-triggered control, where each agent computes its next triggering time in advance without having to observe the system's states continuously. The effectiveness of the theoretical results is illustrated by a numerical example finally. PMID- 26672052 TI - A Bi-Projection Neural Network for Solving Constrained Quadratic Optimization Problems. AB - In this paper, a bi-projection neural network for solving a class of constrained quadratic optimization problems is proposed. It is proved that the proposed neural network is globally stable in the sense of Lyapunov, and the output trajectory of the proposed neural network will converge globally to an optimal solution. Compared with existing projection neural networks (PNNs), the proposed neural network has a very small model size owing to its bi-projection structure. Furthermore, an application to data fusion shows that the proposed neural network is very effective. Numerical results demonstrate that the proposed neural network is much faster than the existing PNNs. PMID- 26672053 TI - Power Quality Analysis Using a Hybrid Model of the Fuzzy Min-Max Neural Network and Clustering Tree. AB - A hybrid intelligent model comprising a modified fuzzy min-max (FMM) clustering neural network and a modified clustering tree (CT) is developed. A review of clustering models with rule extraction capabilities is presented. The hybrid FMM CT model is explained. We first use several benchmark problems to illustrate the cluster evolution patterns from the proposed modifications in FMM. Then, we employ a case study with real data related to power quality monitoring to assess the usefulness of FMM-CT. The results are compared with those from other clustering models. More importantly, we extract explanatory rules from FMM-CT to justify its predictions. The empirical findings indicate the usefulness of the proposed model in tackling data clustering and power quality monitoring problems under different environments. PMID- 26672054 TI - Learn the Lagrangian: A Vector-Valued RKHS Approach to Identifying Lagrangian Systems. AB - We study the modeling of Lagrangian systems with multiple degrees of freedom. Based on system dynamics, canonical parametric models require ad hoc derivations and sometimes simplification for a computable solution; on the other hand, due to the lack of prior knowledge in the system's structure, modern nonparametric models in machine learning face the curse of dimensionality, especially in learning large systems. In this paper, we bridge this gap by unifying the theories of Lagrangian systems and vector-valued reproducing kernel Hilbert space. We reformulate Lagrangian systems with kernels that embed the governing Euler-Lagrange equation-the Lagrangian kernels-and show that these kernels span a subspace capturing the Lagrangian's projection as inverse dynamics. By such property, our model uses only inputs and outputs as in machine learning and inherits the structured form as in system dynamics, thereby removing the need for the mundane derivations for new systems as well as the generalization problem in learning from scratches. In effect, it learns the system's Lagrangian, a simpler task than directly learning the dynamics. To demonstrate, we applied the proposed kernel to identify the robot inverse dynamics in simulations and experiments. Our results present a competitive novel approach to identifying Lagrangian systems, despite using only inputs and outputs. PMID- 26672055 TI - Infrared Ship Target Segmentation Based on Spatial Information Improved FCM. AB - Segmentation of infrared (IR) ship images is always a challenging task, because of the intensity inhomogeneity and noise. The fuzzy C-means (FCM) clustering is a classical method widely used in image segmentation. However, it has some shortcomings, like not considering the spatial information or being sensitive to noise. In this paper, an improved FCM method based on the spatial information is proposed for IR ship target segmentation. The improvements include two parts: 1) adding the nonlocal spatial information based on the ship target and 2) using the spatial shape information of the contour of the ship target to refine the local spatial constraint by Markov random field. In addition, the results of K -means are used to initialize the improved FCM method. Experimental results show that the improved method is effective and performs better than the existing methods, including the existing FCM methods, for segmentation of the IR ship images. PMID- 26672056 TI - Integration of Global and Local Metrics for Domain Adaptation Learning Via Dimensionality Reduction. AB - Domain adaptation learning (DAL) investigates how to perform a task across different domains. In this paper, we present a kernelized local-global approach to solve domain adaptation problems. The basic idea of the proposed method is to consider the global and local information regarding the domains (e.g., maximum mean discrepancy and intraclass distance) and to convert the domain adaptation problem into a bi-object optimization problem via the kernel method. A solution for the optimization problem will help us identify a latent space in which the distributions of the different domains will be close to each other in the global sense, and the local properties of the labeled source samples will be preserved. Therefore, classic classification algorithms can be used to recognize unlabeled target domain data, which has a significant difference on the source samples. Based on the analysis, we validate the proposed algorithm using four different sources of data: synthetic, textual, object, and facial image. The experimental results indicate that the proposed method provides a reasonable means to improve DAL algorithms. PMID- 26672057 TI - Robust $H_{?infty }$ Self-Triggered Control of Networked Systems Under Packet Dropouts. AB - This paper is concerned with robust Hinfinity self-triggered control of networked systems. The system considered here includes parameter uncertainties, packet dropouts, and time delays. The time delay is described in a stochastic way, which takes a value from a given finite set. In order to compensate for the existence of deterministic packet dropouts, a new self-triggered control scheme is proposed. The main feature of the proposed self-triggered control strategy is that the next control task is predicted based on the self-triggered technique, in which the predicted event interval is divided equally for the sake of packet dropouts. The triggered condition is developed to ensure the stability of the uncertain sampled system by utilizing an uncertain algebraic Riccati equation and the comparison principle. Finally, an example of the inverted pendulum of a cart is provided to illustrate the effectiveness of the proposed results. PMID- 26672058 TI - Biomolecular Markers within the Core Axis of Aging and Particulate Air Pollution Exposure in the Elderly: A Cross-Sectional Study. AB - BACKGROUND: Telomere length and mitochondrial DNA (mtDNA) content are markers of aging and aging-related diseases. There is inconclusive evidence concerning the mechanistic effects of airborne particulate matter (PM) exposure on biomolecular markers of aging. OBJECTIVE: The present study examines the association between short- and long-term PM exposure with telomere length and mtDNA content in the elderly and investigates to what extent this association is mediated by expression of genes playing a role in the telomere-mitochondrial axis of aging. METHODS: Among 166 nonsmoking elderly participants, we used qPCR to measure telomere length and mtDNA content in leukocytes and RNA from whole blood to measure expression of SIRT1, TP53, PPARGC1A, PPARGC1B, NRF1, and NFE2L2. Associations between PM exposure and markers of aging were estimated using multivariable linear regression models adjusted for sex, age, BMI, socioeconomic status, statin use, past smoking status, white blood cell count, and percentage of neutrophils. Mediation analysis was performed to explore the role of age related markers between the association of PM exposure and outcome. Annual PM2.5 exposure was calculated for each participant's home address using a high resolution spatial-temporal interpolation model. RESULTS: Annual PM2.5 concentrations ranged from 15 to 23 MUg/m3. A 5-MUg/m3 increment in annual PM2.5 concentration was associated with a relative decrease of 16.8% (95% CI: -26.0%, 7.4%, p = 0.0005) in telomere length and a relative decrease of 25.7% (95% CI: 35.2%, -16.2%, p < 0.0001) in mtDNA content. Assuming causality, results of the mediation analysis indicated that SIRT1 mediated 19.5% and 22.5% of the estimated effect of PM2.5 exposure on telomere length and mtDNA content, respectively. CONCLUSIONS: Our findings suggest that the estimated effects of PM2.5 exposure on the telomere-mitochondrial axis of aging may play an important role in chronic health effects of PM2.5. CITATION: Pieters N, Janssen BG, Dewitte H, Cox B, Cuypers A, Lefebvre W, Smeets K, Vanpoucke C, Plusquin M, Nawrot TS. 2016. Biomolecular markers within the core axis of aging and particulate air pollution exposure in the elderly: a cross-sectional study. Environ Health Perspect 124:943 950; http://dx.doi.org/10.1289/ehp.1509728. PMID- 26672059 TI - Ambient Temperature and the Risk of Preterm Birth in Guangzhou, China (2001 2011). AB - BACKGROUND: Although effects of weather changes on human health have been widely reported, there is limited information regarding effects on pregnant women in developing countries. OBJECTIVE: We investigated the association between maternal exposure to ambient temperature and the risk of preterm birth (< 37 weeks of gestation) in Guangzhou, China. METHODS: We used a Cox proportional hazards model to estimate associations between preterm birth and average temperature during each week of gestation, with weekly temperature modeled as a time-varying exposure during four time windows: 1 week (the last week of the pregnancy), 4 weeks (the last 4 weeks of the pregnancy), late pregnancy (gestational week 20 onward), and the entire pregnancy. Information on singleton vaginal birth between 2001 and 2011 was collected. Daily meteorological data during the same period were obtained from the Guangzhou Meteorological Bureau. RESULTS: A total of 838,146 singleton vaginal births were included, among which 47,209 (5.6%) were preterm births. High mean temperatures during the 4 weeks, late pregnancy, and the entire pregnancy time windows were associated with an increased risk of preterm birth. Compared with the median temperature (24.4 degrees C), weekly exposures during the last 4 weeks of the pregnancy to extreme cold (7.6 degrees C, the 1st percentile) and extreme heat (31.9 degrees C, the 99th percentile) were associated with 17.9% (95% CI: 10.2, 26.2%) and 10.0% (95% CI: 2.9, 17.6%) increased risks of preterm birth, respectively. The association between extreme heat and preterm birth was stronger for preterm births during weeks 20-31 and 32 34 than those during weeks 35-36. CONCLUSIONS: These findings might have important implications in preventing preterm birth in Guangzhou as well as other areas with similar weather conditions. CITATION: He JR, Liu Y, Xia XY, Ma WJ, Lin HL, Kan HD, Lu JH, Feng Q, Mo WJ, Wang P, Xia HM, Qiu X, Muglia LJ. 2016. Ambient temperature and the risk of preterm birth in Guangzhou, China (2001-2011). Environ Health Perspect 124:1100-1106; http://dx.doi.org/10.1289/ehp.1509778. PMID- 26672060 TI - Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012). AB - BACKGROUND: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. OBJECTIVE: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273). METHODS: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. RESULTS: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05). CONCLUSION: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population. CITATION: Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010-2012). Environ Health Perspect 124:1107-1113; http://dx.doi.org/10.1289/ehp.1509870. PMID- 26672062 TI - Dry needling is acupuncture. PMID- 26672061 TI - Recommendations for Evaluating Temporal Trends of Persistent Organic Pollutants in Breast Milk. AB - BACKGROUND: Biomonitoring data of persistent organic pollutants (POPs) in breast milk are increasingly collected and available for quantitative analysis of levels and time trends. A common approach is to apply log-linear regression to calculate doubling and halving times of the POP concentrations based on the temporal trend observed in breast milk. However, there are different, sometimes conflicting interpretations of these doubling and halving times. OBJECTIVES: We provide a mechanistic understanding of doubling and halving times where possible. Five recommendations are proposed for dealing with POP concentration trends in breast milk during three distinct periods (pre-ban, transition, post-ban period). DISCUSSION: Using temporal trends of BDE-47 and PCB-153 in breast milk data, we show which information can be gained from the time-trend data. To this end, we analyzed time trends of hypothetical POPs for different periods with time-variant exposure and different intrinsic elimination half-lives, using a dynamic population-based pharmacokinetic model. Different pieces of information can be extracted from time-trend data from different periods. The analysis of trends of short-lived POPs is rather straightforward and facilitates extraction of the intrinsic elimination half-lives from the breast milk data. However, trends of slowly eliminated POPs only provide indications for the exposure time trend. CONCLUSIONS: Time-trend data of rapidly eliminated POPs provide information on exposure time trends and elimination half-lives. Temporal trends of slowly eliminated POPs are more complicated to interpret, and the extraction of exposure time trends and elimination half-lives require data sets covering several decades. CITATION: Gyalpo T, Scheringer M, Hungerbuhler K. 2016. Recommendations for evaluating temporal trends of persistent organic pollutants in breast milk. Environ Health Perspect 124:881-885; http://dx.doi.org/10.1289/ehp.1510219. PMID- 26672063 TI - Paying attention to the safety and efficacy of fish oil in treatment of knee osteoarthritis. PMID- 26672064 TI - Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study. AB - OBJECTIVE: To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). METHODS: In a 12 week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. RESULTS: Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). CONCLUSIONS: Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. TRIAL REGISTRATION NUMBER: NCT01649999; Results. PMID- 26672065 TI - Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative. AB - OBJECTIVES: The aetiology of bone marrow lesions (BMLs) in knee osteoarthritis (OA) is poorly understood. We employed three-dimensional (3D) active appearance modelling (AAM) to study the spatial distribution of BMLs in an OA cohort and compare this with the distribution of denuded cartilage. METHODS: Participants were selected from the Osteoarthritis Initiative progressor cohort with Kellgren Lawrence scores >=2, medial joint space narrowing and osteophytes. OA and ligamentous BMLs and articular cartilage were manually segmented. Bone surfaces were automatically segmented by AAM. Cartilage thickness of <0.5 mm was defined as denuded and >=0.5-1.5 mm as severely damaged. Non-quantitative assessment and 3D population maps were used for analysing the comparative position of BMLs and damaged cartilage. RESULTS: 88 participants were included, 45 men, mean age (SD) was 61.3 (9.9) years and mean body mass index was 31.1 (4.6) kg/m(2). 227 OA and 107 ligamentous BMLs were identified in 86.4% and 73.8% of participants; OA BMLs were larger. Denuded cartilage was predominantly confined to a central region on the medial femur and tibia, and the lateral facet of the trochlear femur. 67% of BMLs were colocated with denuded cartilage and a further 21% with severe cartilage damage. In the remaining 12%, 25/28 were associated with cartilage defects. 74% of all BMLs were directly opposing (kissing) another BML across the joint. CONCLUSIONS: There was an almost exclusive relationship between the location of OA BML and cartilage denudation, which itself had a clear spatial pattern. We propose that OA, ligamentous and traumatic BMLs represent a bone response to abnormal loading. PMID- 26672066 TI - Treating to target in psoriatic arthritis: how to implement in clinical practice. AB - Treating to target is becoming the standard of care in many medical specialities, including rheumatology. The Tight Control of Psoriatic Arthritis (TICOPA) trial has recently provided evidence of the benefit of treating to target in psoriatic arthritis (PsA), and the revised European League Against Rheumatism (EULAR) recommendations on the management of PsA suggest this approach. However, the question of the optimal measure to use and the practicalities of incorporating this into routine clinical practice remain problematic. PMID- 26672067 TI - A Barley Efflux Transporter Operates in a Na+-Dependent Manner, as Revealed by a Multidisciplinary Platform. AB - Plant growth and survival depend upon the activity of membrane transporters that control the movement and distribution of solutes into, around, and out of plants. Although many plant transporters are known, their intrinsic properties make them difficult to study. In barley (Hordeum vulgare), the root anion-permeable transporter Bot1 plays a key role in tolerance to high soil boron, facilitating the efflux of borate from cells. However, its three-dimensional structure is unavailable and the molecular basis of its permeation function is unknown. Using an integrative platform of computational, biophysical, and biochemical tools as well as molecular biology, electrophysiology, and bioinformatics, we provide insight into the origin of transport function of Bot1. An atomistic model, supported by atomic force microscopy measurements, reveals that the protein folds into 13 transmembrane-spanning and five cytoplasmic alpha-helices. We predict a trimeric assembly of Bot1 and the presence of a Na(+) ion binding site, located in the proximity of a pore that conducts anions. Patch-clamp electrophysiology of Bot1 detects Na(+)-dependent polyvalent anion transport in a Nernstian manner with channel-like characteristics. Using alanine scanning, molecular dynamics simulations, and transport measurements, we show that conductance by Bot1 is abolished by removal of the Na(+) ion binding site. Our data enhance the understanding of the permeation functions of Bot1. PMID- 26672069 TI - KONJAC1 and 2 Are Key Factors for GDP-Mannose Generation and Affect l-Ascorbic Acid and Glucomannan Biosynthesis in Arabidopsis. AB - Humans are unable to synthesize l-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity. PMID- 26672068 TI - Pipecolic Acid Orchestrates Plant Systemic Acquired Resistance and Defense Priming via Salicylic Acid-Dependent and -Independent Pathways. AB - We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. PMID- 26672072 TI - Phosphorylation and Nuclear Localization of NPR1 in Systemic Acquired Resistance. PMID- 26672071 TI - The NIN Transcription Factor Coordinates Diverse Nodulation Programs in Different Tissues of the Medicago truncatula Root. AB - Biological nitrogen fixation in legumes occurs in nodules that are initiated in the root cortex following Nod factor recognition at the root surface, and this requires coordination of diverse developmental programs in these different tissues. We show that while early Nod factor signaling associated with calcium oscillations is limited to the root surface, the resultant activation of Nodule Inception (NIN) in the root epidermis is sufficient to promote cytokinin signaling and nodule organogenesis in the inner root cortex. NIN or a product of its action must be associated with the transmission of a signal between the root surface and the cortical cells where nodule organogenesis is initiated. NIN appears to have distinct functions in the root epidermis and the root cortex. In the epidermis, NIN restricts the extent of Early Nodulin 11 (ENOD11) expression and does so through competitive inhibition of ERF Required for Nodulation (ERN1). In contrast, NIN is sufficient to promote the expression of the cytokinin receptor Cytokinin Response 1 (CRE1), which is restricted to the root cortex. Our work in Medicago truncatula highlights the complexity of NIN action and places NIN as a central player in the coordination of the symbiotic developmental programs occurring in differing tissues of the root that combined are necessary for a nitrogen-fixing symbiosis. PMID- 26672070 TI - Arabidopsis Cell Division Cycle 20.1 Is Required for Normal Meiotic Spindle Assembly and Chromosome Segregation. AB - Cell division requires proper spindle assembly; a surveillance pathway, the spindle assembly checkpoint (SAC), monitors whether the spindle is normal and correctly attached to kinetochores. The SAC proteins regulate mitotic chromosome segregation by affecting CDC20 (Cell Division Cycle 20) function. However, it is unclear whether CDC20 regulates meiotic spindle assembly and proper homolog segregation. Here, we show that the Arabidopsis thaliana CDC20.1 gene is indispensable for meiosis and male fertility. We demonstrate that cdc20.1 meiotic chromosomes align asynchronously and segregate unequally and the metaphase I spindle has aberrant morphology. Comparison of the distribution of meiotic stages at different time points between the wild type and cdc20.1 reveals a delay of meiotic progression from diakinesis to anaphase I. Furthermore, cdc20.1 meiocytes exhibit an abnormal distribution of a histone H3 phosphorylation mark mediated by the Aurora kinase, providing evidence that CDC20.1 regulates Aurora localization for meiotic chromosome segregation. Further evidence that CDC20.1 and Aurora are functionally related was provided by meiosis-specific knockdown of At-Aurora1 expression, resulting in meiotic chromosome segregation defects similar to those of cdc20.1. Taken together, these results suggest a critical role for CDC20.1 in SAC-dependent meiotic chromosome segregation. PMID- 26672073 TI - Systemic Immunity Requires SnRK2.8-Mediated Nuclear Import of NPR1 in Arabidopsis. AB - In plants, necrotic lesions occur at the site of pathogen infection through the hypersensitive response, which is followed by induction of systemic acquired resistance (SAR) in distal tissues. Salicylic acid (SA) induces SAR by activating NONEXPRESSER OF PATHOGENESIS-RELATED GENES1 (NPR1) through an oligomer-to-monomer reaction. However, SA biosynthesis is elevated only slightly in distal tissues during SAR, implying that SA-mediated induction of SAR requires additional factors. Here, we demonstrated that SA-independent systemic signals induce a gene encoding SNF1-RELATED PROTEIN KINASE 2.8 (SnRK2.8), which phosphorylates NPR1 during SAR. The SnRK2.8-mediated phosphorylation of NPR1 is necessary for its nuclear import. Notably, although SnRK2.8 transcription and SnRK2.8 activation are independent of SA signaling, the SnRK2.8-mediated induction of SAR requires SA. Together with the SA-mediated monomerization of NPR1, these observations indicate that SA signals and SnRK2.8-mediated phosphorylation coordinately function to activate NPR1 via a dual-step process in developing systemic immunity in Arabidopsis thaliana. PMID- 26672076 TI - Use of herbarium data to evaluate weediness in five congeners. AB - It is often desirable to quantify a plant's relative weediness or synanthropy, that is, the degree to which a species associates with human-caused disturbance, in order to study and understand the biology, ecology and evolution of weeds and invasive plants. Herbarium specimens are among the most accessible and verifiable sources of data on distribution and habitat. However, the habitat distribution of species may not be reflected accurately by herbarium specimen data, due to well known biases in plant collection. Here, we assess how well herbarium specimens reflect species' weediness, when compared with direct field surveys. We used five species of Melampodium (Asteraceae) and classified their degree of weediness with a modification of Nuorteva's synanthropy index, based on herbarium specimens. We then modelled the distribution of our focal species in Mexico using MaxEnt and identified a polygon of ~3000 km(2) in the state of Nayarit, Mexico, where there was a high probability of finding all five species. Systematic field searches in the target area documented all visible populations of four species along major and minor roads. Then we, again, classified their degree of weediness with the synanthropy index, based now on field data, and compared. We found that herbarium data were an accurate predictor of a species' weediness relative to its congeners despite the well-documented skew of herbarium data towards natural areas, which our data reflected as well. So, herbarium data can be used to classify species' weediness relative to each other, but not in absolute terms, if the specimens were correctly identified and none of the species were subject to particular collection bias. This study is the first attempt to compare herbarium and field data on this subject and may be relevant for other types of investigations based on herbarium data. Our work also highlights the usefulness of distribution models based on herbarium specimens. PMID- 26672075 TI - Genetic diversity and population structure of Arabidopsis thaliana along an altitudinal gradient. AB - The natural genetic variation within a plant species is primarily a consequence of its phylogeography and evolutionary history. This variation largely determines its present-day population structure. Arabidopsis thaliana, as a model plant, has been studied in great detail including its probable origin, local as well as global genetic diversity pattern, population structure, adaptation, etc. However, no such studies have so far been reported from the Indian Himalayan region. Here, we describe a comprehensive study on the genetic diversity and population structure of A. thaliana from an altitudinal range of 700-3400 m above mean sea level the highest altitudinal range reported so far. We also compare these populations with previously reported worldwide populations. A total of 48 accessions representing six populations were analysed using 19 microsatellites and 11 chloroplast markers. Genetic diversity analysis indicated populations to be highly diverse and comparable with worldwide populations. STRUCTURE, principal coordinate and isolation by distance (IBD) analyses showed that genetic variation in different populations is structured at geographical and altitudinal level. Further analyses indicate that these populations are genetically distinct from the rest of the world populations. Different parameters of the demographic expansion model support a rapid expansion. Based on mismatch distribution, the initial time of expansion of west Himalayan populations was found to be about 130 000 years. Bayesian analysis of divergence time indicated that these populations have a long evolutionary history in this region. Based on the results of genetic diversity parameters, demographic expansion and divergence time estimation, it appears that west Himalayan populations may be the source of the west-east expansion model. PMID- 26672074 TI - Glutaredoxin S15 Is Involved in Fe-S Cluster Transfer in Mitochondria Influencing Lipoic Acid-Dependent Enzymes, Plant Growth, and Arsenic Tolerance in Arabidopsis. AB - Glutaredoxins (Grxs) are small proteins that function as oxidoreductases with roles in deglutathionylation of proteins, reduction of antioxidants, and assembly of iron-sulfur (Fe-S) cluster-containing enzymes. Which of the 33 Grxs in Arabidopsis (Arabidopsis thaliana) perform roles in Fe-S assembly in mitochondria is unknown. We have examined in detail the function of the monothiol GrxS15 in plants. Our results show its exclusive mitochondrial localization, and we are concluding it is the major or only Grx in this subcellular location. Recombinant GrxS15 has a very low deglutathionylation and dehydroascorbate reductase activity, but it binds a Fe-S cluster. Partially removing GrxS15 from mitochondria slowed whole plant growth and respiration. Native GrxS15 is shown to be especially important for lipoic acid-dependent enzymes in mitochondria, highlighting a putative role in the transfer of Fe-S clusters in this process. The enhanced effect of the toxin arsenic on the growth of GrxS15 knockdown plants compared to wild type highlights the role of mitochondrial glutaredoxin Fe-S binding in whole plant growth and toxin tolerance. PMID- 26672077 TI - Disparities in Temporal and Geographic Patterns of Declining Heart Disease Mortality by Race and Sex in the United States, 1973-2010. AB - BACKGROUND: Examining small-area differences in the strength of declining heart disease mortality by race and sex provides important context for current racial and geographic disparities and identifies localities that could benefit from targeted interventions. We identified and described temporal trends in declining county-level heart disease mortality by race, sex, and geography between 1973 and 2010. METHODS AND RESULTS: Using a Bayesian hierarchical model, we estimated age adjusted mortality with diseases of the heart listed as the underlying cause for 3099 counties. County-level percentage declines were calculated by race and sex for 3 time periods (1973-1985, 1986-1997, 1998-2010). Strong declines were statistically faster or no different than the total national decline in that time period. We observed county-level race-sex disparities in heart disease mortality trends. Continual (from 1973 to 2010) strong declines occurred in 73.2%, 44.6%, 15.5%, and 17.3% of counties for white men, white women, black men, and black women, respectively. Delayed (1998-2010) strong declines occurred in 15.4%, 42.0%, 75.5%, and 76.6% of counties for white men, white women, black men, and black women, respectively. Counties with the weakest patterns of decline were concentrated in the South. CONCLUSIONS: Since 1973, heart disease mortality has declined substantially for these race-sex groups. Patterns of decline differed by race and geography, reflecting potential disparities in national and local drivers of these declines. Better understanding of racial and geographic disparities in the diffusion of heart disease prevention and treatment may allow us to find clues to progress toward racial and geographic equity in heart disease mortality. PMID- 26672078 TI - Risk Factor Stratification for Intracranial Stenosis in Taiwanese Patients With Cervicocerebral Stenosis. AB - BACKGROUND: Intracranial stenosis (ICS) is a major determinant of ischemic stroke in Asians. We determined the clinical significance of different risk factors and the role of ICS in Taiwanese patients with varied distributions of cervicocerebral stenosis. METHODS AND RESULTS: Presence of extracranial carotid stenosis (ECS, >=70%) and ICS (>50%) was examined in 13 539 patients using ultrasonography and magnetic resonance angiography, respectively. Seven hundred thirty-three patients with non-ECS/ICS (n=372), isolated ICS (n=112), isolated ECS (n=121), or combined ECS/ICS (CEIS, n=128) were selected. Prevalence of ischemic stroke in each group was compared, and risk factors for stenosis were determined. The area under the receiver operating characteristic curve for each risk factor was calculated. Prevalence of ischemic stroke was highest in patients with CEIS (odds ratio 15.86; P<0.001), followed in decreasing order by those with isolated ICS (odds ratio 7.16; P<0.001), isolated ECS (odds ratio 1.77; P=0.011), and non-ECS/ICS. Multivariate logistic regression analysis revealed that hypertension, coronary artery disease, and smoking were risk factors for isolated ECS; hypertension, diabetes mellitus, coronary artery disease, and smoking were risk factors for isolated ICS; and diabetes mellitus, coronary artery disease, and smoking were risk factors for CEIS. Smoking, diabetes mellitus, and coronary artery disease were the greatest contributors to CEIS, isolated ICS, and isolated ECS, respectively. CONCLUSIONS: CEIS was associated with higher odds of ischemic stroke compared with isolated ICS and isolated ECS. Smoking and diabetes mellitus, major determinants of CEIS and isolated ICS, should be targeted in therapeutic strategies to reduce the risk of ischemic stroke. PMID- 26672079 TI - N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Levels are Increased in Patients With Transient Ischemic Attack Accompanied by Nonfocal Symptoms. AB - BACKGROUND: Transient nonfocal neurological symptoms may serve as markers of cardiac dysfunction. We assessed whether serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, a biomarker of cardiac disease, are increased in patients with transient ischemic attack (TIA) accompanied by nonfocal symptoms and in patients with attacks of nonfocal symptoms (transient neurological attack [TNA]). METHODS AND RESULTS: We included 15 patients with TNA, 69 with TIA accompanied by nonfocal symptoms, 58 with large-vessel TIA, 32 with cardioembolic TIA, and 46 age- and sex-matched healthy control participants. Serum NT-proBNP levels were determined within 1 week after the attack. We compared log transformed NT-proBNP levels of patients with cardioembolic TIAs and mixed or nonfocal TNAs, with those of patients with noncardioembolic TIAs as a reference group. Adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease were made with a multiple linear regression model. Compared with large-vessel TIA (mean 14.2 pmol/L), mean NT-proBNP levels were significantly higher in patients with TIA accompanied by nonfocal symptoms (40.5 pmol/L, P=0.049) and with cardioembolic TIA (123.5 pmol/L; P=0.004) after adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease. Patients with TNA also had higher mean NT-proBNP levels (20.8 pmol/L, P=0.38) than those with large-vessel TIA, but this difference was not statistically significant. CONCLUSION: NT-proBNP levels are increased in patients with TIA accompanied by nonfocal symptoms. PMID- 26672082 TI - CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate Personalized Drug for the Immunotherapy of Human Cancer. AB - The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. PMID- 26672080 TI - Efficacy and Safety of Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery. AB - BACKGROUND: Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS. METHODS AND RESULTS: In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30 day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment. CONCLUSION: NCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS. PMID- 26672083 TI - CCR 20th Anniversary Commentary: MAPK/ERK Pathway Inhibition in Melanoma-Kinase Inhibition Redux. AB - In the January 15, 2012, issue of Clinical Cancer Research, Kirkwood and colleagues published a study comparing the MEK inhibitor selumetinib with temozolomide in unselected metastatic melanoma. Although selumetinib did not improve survival or response, most responders had BRAF-activating mutations, and selumetinib has since demonstrated efficacy in BRAF-mutant melanoma. This study laid the groundwork for the evaluation of BRAF/MEK inhibitors in BRAF-mutant melanoma. PMID- 26672084 TI - ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non Small Cell Lung Cancer. AB - The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439-44. (c)2015 AACR. PMID- 26672086 TI - Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib-Letter. PMID- 26672085 TI - Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study. AB - PURPOSE: In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. EXPERIMENTAL DESIGN: Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor), mid-risk (2-3 factors), and high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. RESULTS: For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63-2.24], 1.11 (95% CI, 0.82-1.5), and 0.84 (95% CI, 0.50-1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51-1.83; P = 0.9087), 0.673 (95% CI, 0.5-0.91; P = 0.0094), and 0.536 (95% CI, 0.32-0.905; P = 0.0196), respectively. CONCLUSIONS: This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS). Clin Cancer Res; 21(24); 5480-7. (c)2015 AACR. PMID- 26672087 TI - Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib-Response. PMID- 26672088 TI - Infliximab for IPILIMUMAB-Related Colitis-Letter. PMID- 26672089 TI - Cervical Cancer Prevention and Cancer Control in Latin America-Letter. PMID- 26672091 TI - An interview with Nipam Patel. AB - Nipam Patel is a developmental biologist based at the University of California, Berkeley, USA, where he uses a variety of organisms to study the evolution of developmental systems, from arthropod body plans to butterfly colouration. We asked him about his career and scientific interests, his role as an editor at Development, and his growing butterfly collection. PMID- 26672090 TI - Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC. AB - BACKGROUND AND OBJECTIVES: Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007-2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299). RESULTS: In adults with SCD, eGFR was lower among older individuals: -1.78 ml/min per 1.73 m(2) per year of age (95% confidence interval [95% CI], -2.06 to -1.50; Walk-PHaSST Trial), -1.75 ml/min per 1.73 m(2) per year of age (95% CI, -2.05 to -1.44; MSH), and -1.69 ml/min per 1.73 m(2) per year of age (95% CI, -2.00 to -1.38; CSSCD) in HbSS compared with -1.09 ml/min per 1.73 m(2) per year of age (95% CI, -1.39 to -0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (>=3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function. CONCLUSIONS: In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality. PMID- 26672093 TI - COP9-Hedgehog axis regulates the function of the germline stem cell progeny differentiation niche in the Drosophila ovary. AB - Both stem cell self-renewal and lineage differentiation are controlled extrinsically as well as intrinsically. Germline stem cells (GSCs) in the Drosophila ovary provide an attractive model in which to study both stem cell self-renewal and lineage differentiation at the molecular and cellular level. Recently, we have proposed that escort cells (ECs) form a differentiation niche to control GSC lineage specification extrinsically. However, it remains poorly understood how the maintenance and function of the differentiation niche are regulated at the molecular level. Here, this study reveals a new role of COP9 in the differentiation niche to modulate autocrine Hedgehog (Hh) signaling, thereby promoting GSC lineage differentiation. COP9, which is a highly conserved protein complex composed of eight CSN subunits, catalyzes the removal of Nedd8 protein modification from target proteins. Our genetic results have demonstrated that all the COP9 components and the hh pathway components, including hh itself, are required in ECs to promote GSC progeny differentiation. Interestingly, COP9 is required in ECs to maintain Hh signaling activity, and activating Hh signaling in ECs can partially bypass the requirement for COP9 in GSC progeny differentiation. Finally, both COP9 and Hh signaling in ECs promote GSC progeny differentiation partly by preventing BMP signaling and maintaining cellular processes. Therefore, this study has demonstrated that the COP9-Hh signaling axis operates in the differentiation niche to promote GSC progeny differentiation partly by maintaining EC cellular processes and preventing BMP signaling. This provides new insight into how the function of the differentiation niche is regulated at the molecular level. PMID- 26672092 TI - Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix. AB - Tendons and ligaments are extracellular matrix (ECM)-rich structures that interconnect muscles and bones. Recent work has shown how tendon fibroblasts (tenocytes) interact with muscles via the ECM to establish connectivity and strengthen attachments under tension. Similarly, ECM-dependent interactions between tenocytes and cartilage/bone ensure that tendon-bone attachments form with the appropriate strength for the force required. Recent studies have also established a close lineal relationship between tenocytes and skeletal progenitors, highlighting the fact that defects in signals modulated by the ECM can alter the balance between these fates, as occurs in calcifying tendinopathies associated with aging. The dynamic fine-tuning of tendon ECM composition and assembly thus gives rise to the remarkable characteristics of this unique tissue type. Here, we provide an overview of the functions of the ECM in tendon formation and maturation that attempts to integrate findings from developmental genetics with those of matrix biology. PMID- 26672094 TI - Evidence of Extrapancreatic Glucagon Secretion in Man. AB - Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from alpha-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy. PMID- 26672096 TI - Dogs and asthma. PMID- 26672095 TI - Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat-Fed Diabetic Mice. AB - Dipeptidyl peptidase-4 (DPP4) inhibitors used for the treatment of type 2 diabetes are cardioprotective in preclinical studies; however, some cardiovascular outcome studies revealed increased hospitalization rates for heart failure (HF) among a subset of DPP4 inhibitor-treated subjects with diabetes. We evaluated cardiovascular function in young euglycemic Dpp4(-/-) mice and in older, high fat-fed, diabetic C57BL/6J mice treated with either the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide or the highly selective DPP4 inhibitor MK-0626. We assessed glucose metabolism, ventricular function and remodeling, and cardiac gene expression profiles linked to inflammation and fibrosis after transverse aortic constriction (TAC) surgery, a pressure-volume overload model of HF. Young euglycemic Dpp4(-/-) mice exhibited a cardioprotective response after TAC surgery or doxorubicin administration, with reduced fibrosis; however, cardiac mRNA analysis revealed increased expression of inflammation-related transcripts. Older, diabetic, high fat-fed mice treated with the GLP-1R agonist liraglutide exhibited preservation of cardiac function. In contrast, diabetic mice treated with MK-0626 exhibited modest cardiac hypertrophy, impairment of cardiac function, and dysregulated expression of genes and proteins controlling inflammation and cardiac fibrosis. These findings provide a model for the analysis of mechanisms linking fibrosis, inflammation, and impaired ventricular function to DPP4 inhibition in preclinical studies. PMID- 26672097 TI - Medicines reconciliation: do we know which medicines children are taking? PMID- 26672098 TI - Enter B and W: two new meningococcal vaccine programmes launched. AB - In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone of N. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2. PMID- 26672099 TI - Towards evidence based medicine for paediatricians. PMID- 26672100 TI - Is nasal suctioning warranted before measuring O2 saturation in infants with bronchiolitis? PMID- 26672102 TI - Moderate prematurity and outcome in childhood: there are dangers in jumping to the wrong conclusions. PMID- 26672103 TI - Monotherapy or polytherapy for childhood epilepsies? PMID- 26672104 TI - Does Implant Insertion with a Funnel Decrease Capsular Contracture? A Preliminary Report. AB - BACKGROUND: Capsular contracture remains a common and dreaded complication of breast augmentation. The etiology of capsular contracture is believed to be multi factorial, and its causes may include biofilm formation due to implant/pocket contamination with skin flora. It has been shown that insertion funnel use reduces skin contact and potential contamination by 27-fold in a cadaver model. After incorporating the funnel into our surgical protocols, we anecdotally believed we were experiencing fewer capsular contractures in our augmentation practices. OBJECTIVES: The purpose of this study was to test the hypothesis that capsular contracture related reoperation rates decreased after insertion funnel adoption using data from multiple practices. METHODS: At seven participating centers, we retrospectively reviewed the surgical records from March 2006 to December 2012 for female patients who had undergone primary breast augmentation with silicone gel implants. Group 1 consisted of consecutive augmentations done without the insertion funnel, and Group 2 consisted of consecutive augmentations done with the insertion funnel. The primary outcome variable was development of grade III or IV capsular contracture that led to reoperation within 12 months. RESULTS: A total of 1177 breast augmentations met inclusion criteria for Group 1 and 1620 breast augmentations for Group 2. The rate of reoperation due to capsular contracture was higher without use of the insertion funnel (1.49%), compared to Group 2 with funnel use (0.68%), a 54% reduction (P = 0.004). CONCLUSIONS: The insertion funnel group experienced a statistically significant reduction in the incidence of reoperations performed due to capsular contracture within 12 months of primary breast augmentation. PMID- 26672105 TI - Core Concepts: Biosimilars. PMID- 26672109 TI - Put the healthy item first: Order of ingredient listing influences consumer selection. AB - This study examined effects of an order form intervention on choice of healthy ingredients among college students ordering submarine sandwiches (subs). Over eight weekly sub-nights, college students submitted 9765 orders. The order form format was manipulated in one condition making the healthier selections more salient. Main outcome measures were selection of ingredients. Multi-level logistic regression, chi square, and analysis of variance were used to examine the effect of experimental conditions on selection of ingredients. The health salient form increased selection of healthier and decreased selection of unhealthy ingredients. The manipulation increased fiber, decreased sodium, but did not impact calorie/fat levels of the subs served. PMID- 26672110 TI - Endovascular treatment of intracranial infectious aneurysms in eloquent cortex with super-selective provocative testing: Case series and literature review. AB - Intracranial infectious aneurysms (IIAs) are a rare subgroup of intracranial aneurysms. Often erroneously termed mycotic aneurysms, these lesions most often result from infectious endocarditis and involve the distal anterior cortical circulation. Diagnosis typically follows headaches or septic infarcts, although increasing numbers of lesions are found incidentally, during screening protocols for infectious endocarditis. Open surgical treatment was previously the mainstay of treatment; however, these IIAs are often fusiform and quite fragile, making open surgical obliteration difficult and typically requiring lesion trapping. Current treatment techniques more commonly involve endovascular coil embolization or parent vessel occlusion. Many of these lesions occur distally, in or around the eloquent cortex, making embolization potentially dangerous. We present cases that highlight the use of super-selective provocative testing with sodium amobarbital and lidocaine, to help clarify and predict the risk of parent vessel occlusion in IIAs located in the eloquent cortex. PMID- 26672114 TI - Editor's Letter. PMID- 26672111 TI - Post-traumatic cytotoxic edema is directly related to mitochondrial function. AB - Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function. PMID- 26672115 TI - Changes in Psychological Health and Subjective Well-Being Among Incarcerated Individuals With Serious Mental Illness. AB - While improving the psychological health and well-being of individuals with serious mental illness can help reduce emotional distress and increase resilience, not enough is known about the well-being of incarcerated individuals with mental illness. Using the Schwartz Outcome Scale-10, the authors examined changes in subjective well-being and its association with other clinical symptoms and personality features in 43 mentally ill inmates in a large jail. All participants demonstrated significant improvement in general psychopathology and negative emotions. For well-being, however, different trajectories were associated with high versus low baseline ratings. Furthermore, those in the high well-being group were more likely to show features of aggression, dominance, hostility, mania, and more positive affect. These findings suggest that the level of well-being among inmates with serious mental illness may be an early indicator of personality features, clinical changes, and resilience, which is essential knowledge required when completing effective treatment planning. PMID- 26672116 TI - Chlamydia Screening in Juvenile Corrections: Even Females Considered to Be at Low Risk Are at High Risk. AB - The Centers for Disease Control and Prevention recommends chlamydia screening at intake for all females in juvenile detention facilities. Identifying factors predictive of chlamydia could enable targeted screening, reducing costs while still identifying most infections. This study used demographic, arrest, and health data to identify factors associated with chlamydia among females aged 12 to 18 years entering a juvenile detention facility in San Diego during January 2009 to June 2010. The study created different screening criteria based on combinations of factors associated with infection and calculated sensitivity and proportion screened for each criterion. Overall chlamydia prevalence was 10.3% and was 4.2% among females reporting no sexual risk factors. No acceptable targeted screening approach was identified. High prevalence, even among females without risk factors, supports universal screening at intake. PMID- 26672117 TI - State Laws Governing HIV Testing in Correctional Settings. AB - At the end of 2010, 1.5% of inmates in state prisons were known to be HIV positive, a prevalence rate approximately 3 times that of the general population of the United States. Increased HIV testing in correctional settings has the potential to identify previously undiagnosed infections. This article offers a systematic review and analysis of state laws governing HIV testing in correctional settings, including HIV testing upon admission or prior to release, HIV testing for individuals charged with or convicted of specific crimes, and HIV testing of inmates in situations where contact between the inmate and law enforcement or corrections personnel may have led to an exposure. The implications of these laws for facilitating access to HIV testing within correctional settings are discussed. PMID- 26672118 TI - Characterizing the Burden of Hepatitis C Infection Among Entrants to Pennsylvania State Prisons, 2004 to 2012. AB - Although hepatitis C (HCV) infection is common among prisoners, relatively few undergo evaluation for treatment. This study reports the prevalence of chronic infection and the genotype distribution among an incarcerated population. HCV antibody testing was provided to adults entering Pennsylvania prisons; confirmatory and genotype testing were offered to those eligible for treatment. Antibody prevalence among 101,727 individuals was 18.1%. Among 7,633 individuals who underwent confirmatory testing, 69.3% had detectable RNA. Among 3,247 individuals who underwent genotype testing, genotype 1 was the most common (76.6%). The rate of chronic infection after HCV exposure is similar to that reported in the community, as is genotype distribution. Correctional facilities provide access to a population with a high disease burden, creating a public health opportunity for evaluation and treatment. PMID- 26672120 TI - The Impact of Homelessness and Incarceration on Women's Health. AB - Female inmates have multiple challenges during incarceration and as they transition into the community including: barriers to accessing health care within correctional facilities, poor transitional preparation preceding release, and inadequate continuity of health care after release. This qualitative study explored the health-seeking experiences and the health and housing needs of female inmates. Four focus groups were conducted in a remand facility in Canada. Women described poor health at entry to the correctional system and viewed incarceration as a means to access health care services. Transition back into the community represented a crossroad that was dependent on the stability of housing status. These findings support gender-sensitive health and housing programs to reduce addictions, recidivism, and poor health among this vulnerable population. PMID- 26672119 TI - Expert Opinion and Recommendations for the Management of Attention Deficit/Hyperactivity Disorder in Correctional Facilities. AB - There has been considerably less research on the management of adult attention deficit/hyperactivity disorder (ADHD) among the inmates of correctional facilities than in the general community. While the successful identification and management of ADHD in the adult correctional setting offer potential benefits to the individuals themselves, to institutional staff, and to wider society, their implementation represents significant challenges. These include high prevalence rates, the low level of ADHD recognition, the high incidence of comorbid psychiatric disorders, and the high risk of abuse and diversion of prescribed medications. Here, the authors provide an overview of current recommendations for the identification and management of adults with ADHD in correctional settings and discuss possible strategies for their further development. PMID- 26672121 TI - Fitness Changes After an 8-Week Fitness Coaching Program at a Regional Youth Detention Facility. AB - A Surgeon General's report states that there is a favorable relationship between exercise and chronic disease. Research suggests that exercise programs for elderly inmates may have a positive effect on the number of infirmary visits, which in turn may have a long-term effect on inmate health care costs. This exploratory descriptive double case study sought to add to the minimal information in peer-reviewed research journals by examining the effects of fitness coaching on two juveniles at a youth detention facility in Southwest Montana. The results showed that both participants made fitness improvements following the 8-week program and both perceived positive effects on self-concept and overall sense of well-being from participating in this program. PMID- 26672122 TI - Position Statement: Medical Autonomy and Incident Reporting. PMID- 26672128 TI - JIV Policy on Addressing Diversity in Manuscripts. PMID- 26672126 TI - High-Frequency Acceleration: Therapeutic Tool to Preserve Bone following Tooth Extractions. AB - A common problem in clinical dentistry is the significant and rapid bone loss that occurs after tooth extraction. Currently there is no solution for the long term preservation of alveolar bone. Previously, we showed that high-frequency acceleration (HFA) has an osteogenic effect on healthy alveolar bone. However, it is not known if HFA can preserve alveolar bone after extraction without negatively affecting wound healing. The purpose of this study was to evaluate the effect of HFA on alveolar bone loss and the rate of bone formation after tooth extraction. Eighty-five adult Sprague-Dawley rats were divided into 3 groups: control, static (static load), and HFA. In all groups, the maxillary right third molar was extracted. The HFA group received HFA for 5 min/d, applied through the second molar. The static group received the same magnitude of static load. The control group did not receive any stimulation. Some animals received fluorescent dyes at 26 and 54 d. Samples were collected on days 0, 7, 14, 28, and 56 for fluorescence microscopy, micro-computed tomography, histology, RNA, and protein analyses. We found that HFA increased bone volume in the extraction site and surrounding alveolar bone by 44% when compared with static, while fully preserving alveolar bone height and width long-term. These effects were accompanied by increased expression of osteogenic markers and intramembranous bone formation and by decreased expression of osteoclastic markers and bone resorption activity, as well as decreased expression of many inflammatory markers. HFA is a noninvasive safe treatment that can be used to prevent alveolar bone loss and/or accelerate bone healing after tooth extraction. PMID- 26672127 TI - Evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis. AB - Objectives The aim of the study was to investigate the effect of the non steroidal anti-inflammatory drug meloxicam on the clinical course of obstructive idiopathic cystitis in cats in a placebo-controlled clinical study. Methods Thirty-seven cats with obstructive idiopathic cystitis were enrolled. Cats received supportive treatment and an indwelling transurethral catheter for 48 h. On days 0 and 1, all cats received buprenorphine 0.01 mg/kg subcutaneously every 8 h. On day 1, cats were randomly assigned to the meloxicam (n = 18) or placebo group (n = 19) and received meloxicam (0.1 mg/kg on day 1, 0.05 mg/kg on days 2 5) or placebo orally for five consecutive days. Cats were monitored by repeated physical examinations and urinalysis, and with a 5 day questionnaire filled in by the owners after discharge and a telephone interview 3 months after presentation. Parameters for evaluation of treatment success were the occurrence of recurrent urethral obstruction, results of physical examinations and questionnaires. Results Recurrent urethral obstruction occurred in 4/18 cats (22%) in the meloxicam group and 5/19 cats (26%) in the placebo group ( P = 1.000). General demeanour and pain on abdominal palpation during hospitalisation improved significantly in both groups ( P <0.001). After discharge, with regard to general demeanour, food intake and voiding behaviour, there were no significant differences within or between groups at different time points. Conclusions and relevance Orally administered meloxicam for 5 days did not influence the incidence of recurrent urethral obstruction and the recovery from clinical signs in cats with obstructive feline idiopathic cystitis. The persistence of clinical signs in most of the cats 1 week after initial presentation indicates that symptomatic treatment for a longer period of time is warranted. PMID- 26672131 TI - [Henri Petit (1932-2014)]. PMID- 26672132 TI - Many Molecular Properties from One Kernel in Chemical Space. AB - We introduce property-independent kernels for machine learning models of arbitrarily many molecular properties. The kernels encode molecular structures for training sets of varying size, as well as similarity measures sufficiently diffuse in chemical space to sample over all training molecules. When provided with the corresponding molecular reference properties, they enable the instantaneous generation of machine learning models which can be systematically improved through the addition of more data. This idea is exemplified for single kernel based modeling of internal energy, enthalpy, free energy, heat capacity, polarizability, electronic spread, zero-point vibrational energy, energies of frontier orbitals, HOMO-LUMO gap, and the highest fundamental vibrational wavenumber. Models of these properties are trained and tested using 112,000 organic molecules of similar size. The resulting models are discussed as well as the kernels' use for generating and using other property models. PMID- 26672133 TI - Authors' reply. PMID- 26672134 TI - Authors' response. PMID- 26672135 TI - Bacillus-related Spore Formers: Attractive Agents for Plant Growth Promotion. PMID- 26672136 TI - Author's reply. PMID- 26672137 TI - Authors' reply. PMID- 26672138 TI - How can we play a role in improving animal welfare? PMID- 26672139 TI - Calls for national animal welfare leadership. PMID- 26672140 TI - Hoarding isn't rewarding. PMID- 26672141 TI - GAP greyhounds and blood donations. PMID- 26672142 TI - Assessing the welfare of cows in large dairy herds. PMID- 26672143 TI - Use of whips in horse racing. PMID- 26672144 TI - Response from Melanie Latter, Veterinary Affairs Manager. PMID- 26672145 TI - Preface. PMID- 26672146 TI - Musculoskeletal: What is different in children? Kicked another kid: pain in great toe. PMID- 26672147 TI - Regulation of signal transduction by spatial parameters: a case in NF-kappaB oscillation. AB - NF-kappaB is a transcription factor regulating expression of more than 500 genes, and its dysfunction leads to the autoimmune and inflammatory diseases. In malignant cancer cells, NF-kappaB is constitutively activated. Thus the elucidation of mechanisms for NF-kappaB regulation is important for the establishment of therapeutic treatment caused by incorrect NF-kappaB responses. Cytoplasmic NF-kappaB translocates to the nucleus by the application of extracellular stimuli such as cytokines. Nuclear NF-kappaB is known to oscillate with the cycle of 1.5-4.5 h, and it is thought that the oscillation pattern regulates the expression profiles of genes. In this review, first we briefly describe regulation mechanisms of NF-kappaB. Next, published computational simulations on the oscillation of NF-kappaB are summarised. There are at least 60 reports on the computational simulation and analysis of NF-kappaB oscillation. Third, the importance of a 'space' for the regulation of oscillation pattern of NF-kappaB is discussed, showing altered oscillation pattern by the change in spatial parameters such as diffusion coefficient, nuclear to cytoplasmic volume ratio (N/C ratio), and transport through nuclear membrane. Finally, simulations in a true intracellular space (TiCS), which is an intracellular 3D space reconstructed in a computer with organelles such as nucleus and mitochondria are discussed. PMID- 26672148 TI - Exploiting intrinsic fluctuations to identify model parameters. AB - Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships. Noise in measured data is usually considered to be a nuisance for parameter estimation. However, it turns out that intrinsic fluctuations in particle numbers can make parameters identifiable that were previously non-identifiable. The authors present a method to identify model parameters that are structurally non identifiable in a deterministic framework. The method takes time course recordings of biochemical systems in steady state or transient state as input. Often a functional relationship between parameters presents itself by a one dimensional manifold in parameter space containing parameter sets of optimal goodness. Although the system's behaviour cannot be distinguished on this manifold in a deterministic framework it might be distinguishable in a stochastic modelling framework. Their method exploits this by using an objective function that includes a measure for fluctuations in particle numbers. They show on three example models, immigration-death, gene expression and Epo-EpoReceptor interaction, that this resolves the non-identifiability even in the case of measurement noise with known amplitude. The method is applied to partially observed recordings of biochemical systems with measurement noise. It is simple to implement and it is usually very fast to compute. This optimisation can be realised in a classical or Bayesian fashion. PMID- 26672149 TI - Continuing drug risk behaviour: shared use of injecting paraphernalia among London heroin injectors. AB - The study investigates donor sharing and recipient sharing of different types of injecting equipment and the frequency of sharing activities with sexual partners, close friends and casual acquaintances. Structured interviews were conducted with 303 injectors recruited as part of a study of early and episodic opiate use. Subjects were contacted in non-clinical, community settings by a peer recruitment method (Privileged Access Interviews). Spoons and water containers were more frequently shared than needles and syringes. Significant differences were obtained between the frequency of sharing different types of injecting equipment. Many injectors had shared spoons or water containers, but had not shared needles or syringes. Frequency of sharing with others was also associated with intimacy of relationship to the subject. Almost two-thirds of the sample had shared some sort of injecting equipment during the previous year. The sharing of injecting paraphernalia presents a risk of infection with HIV hepatitis B and hepatitis C. Injectors and drug workers should be more clearly aware of the risks involved in such activities. Harm reduction advice given to drug injectors should target the sharing of injecting paraphernalia. Research into sharing should explicitly include questions about the use of different types of injecting equipment. PMID- 26672150 TI - Evangelical leaders and people with HIV. AB - A concern of much HIV-related public education has been the stigma associated with the disease and campaigns calling for solidarity between people with HIV aim to combat discrimination against them. There is evidence, however, that an influential minority of the population world-wide continues to hold hostile attitudes. The literature reports that religiously committed people are more likely to have less accepting attitudes towards people with HIV. This article thus examines the attitudes of leaders of a growing religious movement, Evangelism, to see (a) whether and in what respects their attitudes differ from the general population; (b) whether they contribute to stigma felt by people with HIV; and (c) how hostile attitudes among this group may be combated. It was found that Evangelical leaders are more likely to attribute blame to people with HIV than are the general population and that this aspect may contribute to stigma felt by people with HIV. In other respects, however, attitudes of Evangelical leaders to people with HIV are not very different to those of the general population and their belief that 'all (humans) have sinned' predisposes many of them to be accepting of, and offer support to, people with HIV. PMID- 26672151 TI - Diabetes quiz. How much do you know about diabetes and CRAVINGS? PMID- 26672152 TI - National Gay Men's HIV/AIDS Awareness Day - September 27, 2015. AB - National Gay Men's HIV/AIDS Awareness Day is observed each year on September 27 to direct attention to the ongoing and disproportionate impact of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) on gay, bisexual, and other men who have sex with men (MSM) in the United States. MSM represent approximately 2% of the U.S. population. However, in 2013, MSM accounted for 67% of all new HIV diagnoses, including 3% who were also injection drug users. PMID- 26672153 TI - Don't Lay Your Eggs All in One Basket: Brood Parasitism as a Survival Strategy. PMID- 26672154 TI - DOJ turns up heat on individuals for illegal coding/billing practices. PMID- 26672156 TI - [THE CHANGES IN FATTY ACIDS COMPOSITION IN THE AUDITORY CORTEX OF RATS AFTER A SINGLE AUDIOGENIC SEIZURE]. AB - We found small but statistically significant increase in the number of stable to peroxide oxidation saturated and monounsaturated fatty acids in the auditory cortex of KM rats in comparison with control Wistar ones. The levels of fatty acids in the cells of the auditory cortex of KM rats were studied at different times (1 h, 1 day, 3 days and 14 days) after a single audiogenic seizure. The changes in fatty acids composition in auditory cortex of KM rats were found already in time point 1 h after convulsion, the maximal decrease of fatty acids levels was observed at 3 days after convulsion. These data suggest that the fatty acids pool in this time was depleted. Finally, we found the recovery of the better part of fatty acids in the auditory cortex of KM rats to 14 day after convulsion. These results can be used for development of new approaches to eliminate brain damage after seizures. PMID- 26672155 TI - [MODIFICATION OF MESENCHYMAL STEM CELLS AS A WAY TO IMPROVE THE EFFECTIVENESS OF CELL THERAPY OF ISCHEMIC MYOCARDIAL INJURY]. AB - Acute myocardial infarction remains to be one of the most important problems of health care. Cardiac cell therapy is a new therapeutic strategy focused on repair of the injured cardiac muscle. Mesenchymal stem cells (MSC) are considered as the most suitable candidates for cardiac cell therapy. MSC transplantation in the myocardium after ischemic injury has been shown to be cardioprotective in animal models and clinical trials. However, the beneficial effects of MSC in humans are limited because of both poor survival and impaired function of the cells in ischemic tissue. To address these issues, a number of approaches to the modification of MSCs with the aim to improve their survival and proliferation, reduce the immune reaction, enhance transdifferentiation, and optimize the profile of secreted paracrine factors have been tested. In this review, we provide detailed discussion of different methods of MSCs modification, including targeted gene overexpression, conditioning of MSCs using physical and chemical factors, and application of multicellular units for transplantation. The effectiveness of these strategies in preclinical studies is also discussed. PMID- 26672157 TI - [CHANGES BLOOD GAS AND OF FREE RADICAL OXIDATION OF LIPIDS IN THE MYOCARDIUM DURING ADAPTATION TO PHYSICAL STRESS]. AB - The article considers the changes of gas composition, acid-base blood balance, lipid peroxidation processes, and activity of the antioxidant defense system in rat myocardium in the course of adaptation to physical activity (swimming). It has been found out that during the first five days physical activity is accompanied by hypoxia, acidotic blood changes, and increase of lipid peroxidation processes in myocardium. Adaptation to swimming activity (15-30 days) leads to hypoxic and acidotic blood changes, and increases antioxidant defense system in myocardium. PMID- 26672158 TI - [STRESS AND INFARCT LIMITING EFFECTS OF EARLY HYPOXIC PRECONDITIONING]. AB - It was established that early hypoxic preconditioning is an adaptive state different from eustress and distress. Hypoxic preconditioning has the cross effects, increasing the tolerance of the heart to ischemia-reperfusion and providing antiulcerogenic effect during immobilization stress. PMID- 26672159 TI - [THE USING OF THE METHOD OF RECONSTRUCTION OF OPTICAL CROSS SECTIONS FOR INVESTIGATION OF THE TROPHOTROPIC EFFECTS OF ADRENALINE AND ATENOLOL]. AB - The trophotropic effects of epinephrine and atenolol were investigated by using the organotypic culture method combined with the method of the reconstruction of optical cross sections. For the best possible image contrast was experimentally established the correction for Petri dish bottom thickness equal to 1 mm (objective lens Carl Zeiss). It was shown by method of the reconstruction of optical cross sections that growth zone in organotypic culture forms a multidimensional structure. In the presence of atenolol (10(-4) M) the thickness of the growth zone of the cardiac tissue explants was above the reference value 212%. The thickness of the growth zone in the presence of epinephrine (10(-9)-10( 13) M) did not differ from the control values. Experimentally was proved that atenolol mimics the trophotropic effects of epinephrine and these effects of epinephrine is realized primarily through beta1-adrenergic receptors. PMID- 26672160 TI - [DYNAMICS OF CYTOKINE CONCENTRATION IN THE BLOOD OF RATS WITH VARIOUS BEHAVIORAL CHARACTERISTICS AFTER ACUTE EMOTIONAL STRESS]. AB - This work was designed to study a change in cytokine content in the peripheral blood of behaviorally passive and active Wistar rats at various time intervals after acute stress on the model of night-time immobilization. A decrease in the concentration of most pro- and anti-inflammatory cytokines in passive animals was most pronounced immediately and, particularly, 3 days after stress exposure. Variations in the blood cytokine profile after experimental stress were lower in behaviorally active specimens. A statistically significant decrease was observed only in the amount of a proinflammatory cytokine IL-1alpha and anti-inflammatory cytokines IL-4 and IL-13. As differentiated from passive rats, these changes in active specimens were most pronounced 1 day after negative emotiogenic exposure. Our results illustrate a specific involvement of immunoactive substances in the systemic regulation of physiological functions and development of individual resistance to the negative consequences of stress. PMID- 26672161 TI - [NORADRENALINE-EVOKED RESTORATION OF THE NEUROGENIC VASOREACTIVITY DIMINISHED BY ACIDOSIS]. AB - The effect of 0.03-1.0 MUM noradrenaline on the neurogenic contractile response to electrical field stimulation of the juvenile rat tail artery segment in control conditions and after the solution pH decrease from 7.4 to 6.6 was studied. Acidosis were shown to inhibit this response significantly at all frequencies of stimulation used (3, 5, 10, and 40 Hz). Noradrenaline potentiated neurogenic vasoconstriction diminished spontaneously or by low pH. The potentiative effect of noradrenaline in acidic solution was more pronounced at higher frequencies of stimulation and noradrenaline concentrations. This phenomenon can, at least in part, account for blood flow redistribution from less important organs to vital ones during exercise which is characterized by acidosis, augmented sympathetic nerve activity and increased levels of noradrenaline. PMID- 26672162 TI - [EFFECT OF LIPOPOLYSACCHARIDE ON NEUTRAL LIPID METABOLISM AND CELLULAR ENERGETICS IN FROG URINARY BLADDER EPITHELIAL CELLS]. AB - It was shown previously that colonization of the frog urinary bladder by gram negative bacteria leads to decreased ability of antidiuretic hormone to reabsorb water from the urinary bladder (Fock et al. J. Exp. Zool., 2013, 319A: 487-494). In the present work performed on epithelial cells isolated from the frog urinary bladder the influence of E. coli lipopolysaccharide (LPS) on neutral lipid metabolism and cellular energetics was studied. It was shown that incubation of cells with LPS led to decrease of fatty acids oxidation and to retention of triacylglycerols (TAG) followed by an increase of the cytoplasmic lipid droplets content and cellular amount of TAG. Fatty acid composition of TAG was not changed under LPS. LPS did not alter mitochondrial membrane potential, however, LPS decreased oxygen consumption rate both in basal and uncoupling conditions. Cellular ATP production was also reduced in the presence of LPS. The data obtained indicate that a decreased ability of antidiuretic hormone to reabsorb water from the urinary bladder induced by bacterial pathogens could be related to inhibition of fatty acids oxidation and impaired energy metabolism. PMID- 26672163 TI - [CORRELATIONS BETWEEN EEG AND RHEOGRAPHIC INDICES OF CEREBRAL BLOOD FLOW IN CHILDREN ON NORTH-EAST OF RUSSIA]. AB - The purpose of the work was an estimation of correlations between EEG spectral parameters and rheoencephalogram (REG) indicators of cerebral blood flow (CBF) in the group of children of 7-18 years old living in the North-East of Russia. Well known data were confirmed about age-dependent EEG and REG-CBF indicators dynamics. It was not revealed strong coordination between EEG and REG age dependent changes in this period of life. This may to our opinion speak of relative independence of development of those systems which reflect itself in EEG and REG--structural functional organization of the brain and cerebral metabolic rate. In a narrow age band 14.8-15.6 years old it was found highly significant positive correlation between EEG theta activity and REG amplitude-frequency parameter--indicating CBF. The hypothesis was suggested explaining this fact from the point of view of the down-regulation mechanism of the brain in the period of energy expensive synthetic processes in puberty period. PMID- 26672164 TI - [ACTIVE AND PASSIVE DISCRIMINATION OF MOVING SOUNDS: EVENT-RELATED RESPONSES OF HUMAN BRAIN]. AB - The current study investigates auditory event-related potentials (ERPs) and mismatch negativity (MMN) during active and passive discrimination of stationary and moving sound stimuli presented according to the oddball paradigm. Standard stimuli represented stationary midline sounds. Deviant stimuli simulated sound source location shifts (to the left/right from head midline) produced by linear or stepwise changes of interaural time delay (ITD). The event-related responses were evaluated by peak amplitudes of N1 waves and mean amplitudes of MMN, P3a, P3b and reorienting negativity (RON) components. The N1 amplitude was larger in active than in passive conditions, and was unaffected by spatial dynamic changes of the deviant stimuli. The deviant motion pattern (smooth or stepwise) affected only MMN and RON obtained in passive listening conditions. Abrupt deviant displacement elicited larger MMN and RON components than smooth motion. Drawing listeners' attention to the deviant stimuli resulted in suppression of MMN/RON sensitivity to auditory motion pattern. PMID- 26672165 TI - Restrictions on Health Navigators May be Easing Up in Some States. PMID- 26672166 TI - Navigators of Cancer Terrain Help Patients--And May Cut Costs. PMID- 26672168 TI - Sure, They're Cool, but Will Smart Wearables Ever Live Up to Their Potential? PMID- 26672169 TI - Hospitalists Are Changing Care Both in And Outside the Hospital. PMID- 26672167 TI - New Cancer Drugs Shine, but Costs May Dim Luster. PMID- 26672170 TI - Employers want more guidance on how clinics fit in with Cadillac tax. PMID- 26672171 TI - New Stent Leaves No Polymer Behind. PMID- 26672172 TI - Medicare Advantage Fraud: Temptation, Consequence, and Protection. PMID- 26672173 TI - Changes in Patterns of Utilization and Cost of Health Care Services Associated With Initiation of Asenapine for the Treatment of Schizophrenia in Adults. AB - PURPOSE: To examine changes in patterns of utilization and cost of health care services associated with initiation of asenapine for the treatment of schizophrenia in adults. DESIGN: Retrospective cohort study using 2 large US health care claims databases. METHODOLOGY: All adults who initiated therapy with asenapine between Aug. 1, 2009, and Dec. 31, 2012, were identified; the date of the earliest claim for asenapine during this period was deemed the index date. Patients without >=1 claims with a schizophrenia diagnosis within 12 months prior to the index date were excluded. We compared patterns of utilization and cost of health care services between 6-month periods immediately before and after index date ("preindex"and "postindex" respectively). RESULTS: 366 patients were identified who initiated asenapine and who met all other selection criteria; mean (SD) age was 40.5 (16.3) years and 57.1% were women. Relative to preindex, patients were less likely during postindex to be hospitalized (41.8% vs 26.2%, P<.001) or to visit the emergency room (24.9% vs 18.9%, P=.03). Mean (SD) total health care costs decreased by $4776 in the postindex period ($16,811 [$26,176] vs $12,035 [$17,037] during preindex), primarily due to a decrease in inpatient costs ($10,616 [$24,977] vs $5286 [$15,846]); mean pharmacy costs increased by $828 ($3656 [$3309] vs $4482 [$3,073]) (all P<.001). CONCLUSION: Use of asenapine for the treatment of schizophrenia was associated with reduced levels of health care utilization and cost during the 6-month period immediately following therapy initiation, primarily due to reduced levels of inpatient care. PMID- 26672174 TI - The taming of cardiovascular disease: Less deadly but could be even more so. PMID- 26672175 TI - [Will bilateral mastectomy replace conservative surgery?]. PMID- 26672176 TI - [Contraception during the perimenopause: indications, security, and non contraceptive benefits]. AB - Although patients' fertility is diminished in the period of perimenopause, they still need efficient contraception. Thorough knowledge of the physiological changes occuring during this period of transition is essential in order to provide optimal care. Until the age of 50, no contraceptive method is specifically considered unsuitable due to age alone. The choice of contraceptive needs to be adapted to the patient, assessing the individual risk factors and favouring the potential non-contraceptive advantages of the method selected. Long term contraceptive methods (e.g., the copper intrauterine device (IUD), the Mirena IUD or a subcutaneous implant) offer an excellent solution on both levels. PMID- 26672178 TI - [Current developments in uterine cervical carcinoma prevention and screening]. AB - The causality between the HPV infection and the carcinoma of the uterine cervix is demonstrated. The benefits of the prophylactic HPV vaccine are emerging in the general population. This vaccine has no evident general side effect. So it is proposed for young women and young men. The commercialization of a nonavalent vaccine will increase its preventive activity. Already, international societies recommend using the HPV test for cervical carcinoma screening in replacement of the cytology in women more than 30-35 years old. In case of negative test, the interval between screenings can be increase until 5 years. In case of positive test, the cervical cytology is used for the triage, but other tests are under development. Due to the vaccine efficacy, the future modalities and the cost/benefits ratio of the screening should be questioned. PMID- 26672177 TI - [Will a vaccine against Chlamydia trachomatis be available soon?]. AB - Chlamydia trachomatis is the most prevalent cause of sexually transmitted bacterial infections worldwide, with more than 100 million estimated cases annually. This obligate intracellular pathogen is known to cause pelvic inflammatory disease (PID) and chronic infections resulting in tubal factor infertility and ectopic pregnancy. However, the majority of the infections remains asymptomatic and thus untreated. For this reason, the ultimate goal for the prevention C. trachomatis infections is an effective vaccine. Here we review the major challenges and the different strategies associated with the development of an anti-Chlamydial vaccine. Even if an effective vaccine is not available yet, recent advances in the understanding of C. trachomatis pathogenesis and mucosal immune system are promising for its future development. PMID- 26672179 TI - [Prevention of preterm birth with vaginal progesterone in women with preterm labor: which are the evidences?]. AB - The presence of uterine contractions and a short cervix at less than 37 weeks of gestation (preterm labor) is an important risk factor for a preterm birth. Currently, there is not treatment able to reduce the risk of preterm birth in this high risk group of women. Vaginal progesterone has been shown to be effective in reducing the risk of preterm birth in asymptomatic women with a prior preterm birth and in women with a short cervix, measured by vaginal ultrasound before 24 weeks of gestation. Unfortunately, vaginal progesterone has not been shown to be efficacious in women with preterm labor. A recent clinical trial has shown that it can even be deleterious in this group of women. PMID- 26672180 TI - [Induction of labour: benefits and risks]. AB - A large proportion of pregnant women have induction of labour at or near term. Few randomized trials have evaluated the various indications to induce labour. In some cases, induction is highly recommended to avoid a life-threatening complication for the fetus or the mother. In other cases, the indication is controversial. We review the evidence for a benefit in case of post-term, premature rupture of membranes, maternal hypertensive disorders and suspicion of fetal macrosomia. In case of maternal diabetes or intrauterine growth impairment the need for induction of labour must probably be discussed according to the clinical features. In the above mentioned indications, it does not seem that the risk of caesarean section is increased. PMID- 26672181 TI - [Overactive bladder syndrome--a public health challenge]. AB - Overactive bladder is a highly prevalent clinical syndrome affecting up to 17% of women. It is often associated with urodynamic detrusor overactivity, leads to embarrassment and is frequently under-diagnosed and insufficiently treated. Its pathophysiology is complex and the numerous treatment modalities, some of them of poor evidence, aim to improve quality of life. When physiotherapy fails, anticholinergics are recommended as first-line medical treatment. They can be combined with or replaced by beta3-adrenergic agonists whereas sacral neuromodulation or posterior tibia nerve stimulation are considered an efficient alternative. Addidtionally, cystoscopic injection of botulinum toxine in the bladder has recently been validated in Switzerland as a treatment option for idiopathic overactive bladder. PMID- 26672182 TI - [Cervical disc herniation--diagnosis and treatment]. AB - A cervical disc herniation (CDH) is a frequently encountered pathology in primary care medicine. It may give rise to a compression of a nerve root (a radiculopathy, with or without sensory-motor deficit) or of the spinal cord (myelopathy). The majority of CDHs can be supported by means of a conservative treatment. When a radiculopathy is found and a clinico-radiological correlation is present, a moderate neurological deficit appears suddenly, or if it is progressive under conservative treatment or if pain is poorly controlled by well conducted conservative treatment performed during 6 to 8 months, surgery is then recommended. A symptomatic cervical myelopathy is, by itself, an indication for a surgical treatment. PMID- 26672184 TI - [Nighttime artificial light and disorders of the human internal clock (1)]. PMID- 26672183 TI - [Risk scores for the development of venous thromboembolism in ambulatory patients and in patients hospitalized for acute medical disease]. AB - The recognition of an increased risk of VTE following surgery has initiated a similar investigation in: 1) Ambulatory subjects. In this group, the Qthrombosis score has identified 8 to 11 risk factors. The incidence of VTE is of the order of 0,15%/year. 2) The patients admitted to hospital for an acute medical disease. Nine scores are available for analysis. Results are difficult to interpret because of confusing factors: the inclusion of symptomatic VTE only or both symptomatic and asymptomatic VTE; the uncontrolled prescription of thromboprophylaxis. VTE incidence over 3 months varies between 15 and 0,5%, but is around 1% in the most recent studies. New studies, with a more rigorous methodological approach, are needed. PMID- 26672185 TI - [Less is more--less is nothing]. PMID- 26672186 TI - [How to end a supraventricular tachycardia without risk to the practice?]. PMID- 26672187 TI - [Breast cancer screening: involving women in medical controversy?]. PMID- 26672188 TI - [Association of alcohol consumption with the risk of death from colorectal cancer]. PMID- 26672189 TI - [Gynecologic, virologic, and malarial miscellany]. PMID- 26672190 TI - [To train more physicians, the faculty of Lausanne and Geneva unite at EPFL]. PMID- 26672191 TI - [Medical secret in prison: the AMG opposes the bill]. PMID- 26672192 TI - [Watson, medicalized artificial intelligence]. PMID- 26672193 TI - [Affinity capillary electrophoresis for screening proteins interacting with domoic acid]. AB - Domoic acid (DA) is a biological neurotoxin that causes amnesic shellfish poisoning. Study of the interactions between DA and important functional proteins contributes to understand the toxicity mechanism of DA to biological macromolecules. In this paper, the interactions between DA and nine important proteins in plasma, intestine and mitochondria were qualitatively compared by affinity capillary electrophoresis. Proteins were used as affinity ligands while DA as the affinity receptor. Proteins with the concentrations of 0, 0.2, 0.4, 0.6, 0.8 MUmol/L were added in the electrophoresis buffer and the migration times of 0.2 mg/mL DA were detected. Then the linear graphs of the variation of DA mobility ratio (DeltaM) with the protein mass concentration (L) were drawn. According to the slope value, the relative strength of the interactions between DA and proteins was compared. The results showed that six proteins can interact with DA and the relative strength order was human thrombin > cytochrome C trypsin immunoglobulin E (Ig E) ~ ribonuclease A > lambda exonuclease, while ferritin, transferrin and lectin had no affinity with DA. With the advantages of high efficiency, fast analysis and less sample consumption, affinity capillary electrophoresis is a convenient method for screening DA target proteins, which will provide basic information for the toxic mechanism and defence of DA. PMID- 26672194 TI - [Preparation of an agglomerated ion chromatographic stationary phase with 2,3 ionene and its application in SO4(2-) analysis]. AB - The poly-electrolyte cation functional group of 2,3-ionene was synthesized with tetramethyl ethylenediamine and 1,3-dibromopropane as the raw materials. Multiporous polystyrene-divinylbenzene microsphere particles (PS-DVB) were produced by swelling method with polystyrene as seeds and sulfonated. Then the 2,3-ionene was bonded on the sulfonated multi-porous polystyrene-divinylbenzene microsphere particles by agglomeration to get the agglomerative ion-exchange stationary phase. After optimizing the synthetic conditions, the new stationary phase was characterized by the techniques including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The chromatographic column was packed by slurry method and applied in the analysis of SO4(2-) with a conductivity detector. SO4(2-) and other six common anions including F-, Cl-, NO2(-), Br-, NO3(-), PO4(3-), were separated and analyzed rapidly on the self-regulating chromatographic column within 8 min. The linear range was from 0.5 to 50 mg/L with correlation coefficient (r) of 0.9992. The LOD was 0.04 mg/L with S/N of 3. The relative standard deviations (RSDs, n = 6) were 2.4% and 3.1% for the peak area and retention time, respectively. The recoveries were between 99.2% and 101.8%. The retention times of SO4(2-) did not change significantly after long time use of the self-regulating chromatographic column. The self-regulating chromatographic column is suitable for the detection of SO4(2 ) in complex matrix samples. PMID- 26672195 TI - [Application of ultra high performance liquid chromatography-mass spectrometry to metabolomics study of drug-induced hepatotoxicity]. AB - Drug-induced hepatotoxicity is a worldwide health issue. And diagnosing the injury in the early stage is still a challenge in clinic. In this study, pattern recognition analysis of the ultra high performance liquid chromatography-mass spectrometry (UPLC-MS) of hepatocytes HL7702 was performed to develop differential metabolites related to hepatotoxicity induced by hepatotoxicants, including carbon tetrachloride (CCl4), acetaminophen (APAP), emodin, aristolochic acid (AA) and triptolide. Hepatocytes injuries were induced by 48 h of treatment with CCl4 (4 mmol/L), APAP (6.5 mmol/L), emodin (14 MUmol/L), AA (35 MUmol/L) and triptolide (18 nmol/L), separately. Global metabolomics profiling, multivariate analysis and database searching were performed to discover common differential metabolites for live injury. The positive hepatoprotective drug, bifendate, was used to repair triptolide induced hepatocytes injury, and bifendate-induced changes of hepatotoxicity-related metabolites were investigated. In the results, fatty acid oxidation and cellular oxidative stress-related metabolites, including nicotinamide adenine dinucleotide and glutathione were significantly changed between the control and hepatotoxicant-treated groups, and after treatment with bifendate, those perturbed metabolites all partly returned to normal level. In conclusion, we discovered potential hepatotoxicity-related metabolites that could be used to evaluate hepatotoxicity induced by chemicals, drugs and traditional Chinese medicines. This study also proved that metabolomics is one of the effective tools to investigate drug-induced hepatotoxicity. PMID- 26672196 TI - [Simultaneous qualitative and quantitative determination of seven anticoagulant rodenticides in whole blood and urine samples using on-line solid phase extraction with liquid chromatography-linear ion trap mass spectrometry]. AB - A new and sensitive analytical method has been developed for the simultaneous determination of seven anticoagulant rodenticides in whole blood and urine samples by liquid chromatography-linear ion trap mass spectrometry (LC-LIT/MS) with on-line solid phase extraction (on-line SPE). The samples were treated with acetonitrile, followed by dilution, centrifugation, and filtration. The resulting solution was injected into the LC system directly and processed by on-line SPE column for enrichment and purification. Separation was performed on a C18 column with mixed mobile phases of methanol and 0.02 mol/L ammonium acetate aqueous solution for gradient elution. The analytes were detected by the mass spectrometer with electrospray ionization (ESI) in negative mode. MS2 full scan signals of the target parent ions within the locked retention time window were recorded. Self-built database searching was performed for qualitative confirmation, and MS2 fragment ions with high sensitivity and specificity were selected for quantification. Simultaneous qualitative and quantitative analyses of the seven rodenticides were achieved in this way. Good linearities were obtained within the investigated mass concentration ranges of the seven rodenticides, with r2 >= 0.9958 in blood and r2 >= 0.9946 in urine. The LODs varied from 0.02 ng/mL to 1.00 ng/mL, and the LOQs varied from 0.10 ng/mL to 4.00 ng/mL. The recoveries at three spiked levels in blood and urine samples ranged from 81.0% to 113.9%, with RSDs of 0.1%-6.2% (n = 6). The developed method is simple, sensitive, and can be used for the rapid detection and accurate quantification of the seven anticoagulant rodenticides in whole blood and urine samples. PMID- 26672197 TI - [Determination of N6-(4-hydroxybenzyl) adenine riboside in rat plasma by ultra performance liquid chromatography-quadrupole time of flight mass spectrometry]. AB - An ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) method was developed and validated for the determination of N6-(4-hydroxybenzyl) adenine riboside and its pharmacokinetics in rat plasma. The chromatographic conditions were optimized. The separation was performed on an Agilent ZORBAX SB-C18 column(150 mm x 3 mm, 1.8 MUm) with a gradient elution of 0.2% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases at a flow rate of 0.35 mL/min. The detection was accomplished in positive mode with electrospray ionization (ESI) by UPLC-QTOF-MS, and 6 benzylamino purine was used as the internal standard (IS). The results showed that the linear range of calibration curve was 0.625-160 ng/mL for N6-(4 hydroxybenzyl) adenine riboside in rat plasma with the correlation coefficient more than 0.99. The recoveries were 88.41%-108.26%. The limit of detection was 0.1 ng/mL. The intra-day and inter-day precisions (RSDs) were less than 6%, and intra-day and inter-day accuracies (REs, RE = (measured concentration-spiked concentration)/spiked concentration x 100%) were less than +/-15%. The method is rapid, sensitive and accurate for the quantitation of N6-(4-hydroxybenzyl) adenine riboside, which can be used for the study of pharmacokinetics of N6-(4 hydroxybenzyl) adenine riboside. PMID- 26672198 TI - [Detection and identification of major metabolites of clorprenaline in swine urine using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry]. AB - This study was conducted to detect and identify the metabolites of clorprenaline in swine urine using ultra-performance liquid chromatography-quadrupole time-of flight mass spectrometry (UPLC/Q-TOF MS), and the major metabolic pathways of clorprenaline were proposed. The swines were administered a single dose each of 10 mg/kg b. w. clorprenaline by oral gavage. The urine samples were collected before and after administration. After a simple preparation, the urine samples were analyzed using UPLC/Q-TOF MS. Combined with data processing techniques including extracted ion chromatography (EIC) and mass defect filtering (MDF), two phase I and seven phase II metabolites were detected in the urine samples collected 0-24 h after administration. The structures of detected metabolites were elucidated by comparing their characteristic product ions with those of the parent clorprenaline. Based on the identified metabolites, the metabolic pathways of clorprenaline included hydroxylation, glucuronidation and sulphate conjugates. Among those detected metabolites, hydroxylated-clorprenaline and its conjugates were responsible for over 60% of the total MS responses, much greater than those of clorprenaline, and were proposed as the primary metabolites in swine urine. This study can provide scientific basis for determining appropriate marker residues of clorprenaline, and facilitate to effectively control clorprenaline residues in animals. PMID- 26672199 TI - [Determination of three coriaria lactones in honey by ultra high performance liquid chromatography-high resolution mass spectrometry]. AB - A method for the determination of three coriaria lactone residues in honey was developed using ultra high performance liquid chromatography-high resolution mass spectrometry. The honey samples were extracted with 0.2 mol/L phosphate buffer solution (pH = 7.5), and the extracts were cleaned up with Waters HLB solid phase extraction cartridges. The extracted components were separated on a Phenomenex C18 column by gradient elution. The qualitative and quantitative analyses were operated under t-MS2 by high resolution mass spectrometry. The results showed that the limits of detection and quantification for the three coriaria lactones in a spiked blank honey were 0.05 mg/kg and 0.1 mg/kg, respectively. The recoveries of the three coriaria lactones spiked in blank honey samples at the levels of 0.1 to 0.5 mg/kg were 86.3%-95.6% with the RSDs of 3.0%-8.4%. The method was applied for the determination of the manuka honey from New Zealand, and tutin was detected in one of the samples. The results showed that the method is suitable for the determination of the three coriaria lactone residues in honey. PMID- 26672200 TI - [Analysis of 17 cytokinins in rice by solid phase extraction purification and liquid chromatography-tandem mass spectrometry]. AB - A method was developed for the determination of 17 cytokinins in rice by solid phase extraction and liquid chromatography-tandem mass spectrometry. The rice samples were cryogenically ground under liquid nitrogen and extracted with methanol-water (80:20, v/v) at 4 degrees C for 16 h. The supernatant was purified on a column packed with polymer cation exchange resin (PCX). The samples were transported and eluted on an analytical column ZORBAX Extend-C18 (100 mm x 2.1 mm, 1.8 MUm) by methanol and 5 mmol/L ammonium formate aqueous solution. All the analytes were detected in selected reaction monitoring (SRM) mode under positive electrospray ionization (ESI+) and quantified by external standard method. The separation conditions were optimized in order to achieve the sufficient separation for the several isomers of cytokinins, such as trans-zeatin 7-glucoside (tZ7G), trans-zeatin-9-glucoside (tZ9G), and trans-zeatin-O-glucoside (tZOG). Moreover, the extraction efficiency of different extraction solvents and clean-up effects of PCX cartridge for each analyte were further investigated. The results showed that the correlation coefficients were not less than 0.9984 in the linear range, and the limits of detection were ranged from 0.01 to 0.05 ng/g. The mean recoveries of the 17 cytokinins at three spiked levels of 0.2, 1 and 5 ng/g were from 60.2% to 125.4% with the relative standard deviations (RSDs) of 5.4% 29.7% (n = 6). Finally, five endogenous cytokinins were successfully quantified in real sample, and their contents were between 0.02 and 0.93 ng/g. It means that this method is reliable for quantitative analysis of cytokinins in rice. PMID- 26672201 TI - [Simultaneous determination of ten antibiotics in pharmaceutical wastewater using ultra-high performance liquid chromatography-tandem mass spectrometry]. AB - A simultaneous analytical method was established for ten selected antibiotics from three categories in pharmaceutical wastewater with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The water samples were enriched and cleaned-up by solid phase extraction cartridges. The types of solid phase extraction cartridges and eluents were optimized by comparing the recoveries of the analytes in water samples under different conditions. The target compounds were separated on an Agilent C18 column (75 mmx 2.1 mm, 2.7 MUm) with the mobile phases of acetonitrile and 0.2% (v/v) formic acid aqueous solution, and then determined by electrospray ionization mass spectrometry (ESI MS). The results showed that the calibration curves were linear in the range of 0.1-1000 MUg/L (r2>0.995). The limits of detection (LODs, S/N>=3) and the limits of quantification (LOQs, S/N>=10) of the ten compounds were 0.07-4.37 ng/L and 0.22-14.55 ng/L, respectively. The recovery experiments were performed with samples spiked in the range of 0.002-40 MUg/L. The recoveries of the target compounds were in the range of 50.4%-114.1% (RSDs<=9.89%, n=3). Based on this analytical method, the raw and treated sewage samples from a pharmaceutical manufacturer wastewater treatment plant in Jiangsu Province were analyzed. Three compounds were detected in the samples from different sewage treatment units in the range of 0.46-1033.60 MUg/L. It shows that the method is accurate, reliable, highly sensitive and can be used to analyze the water samples of pharmaceutical wastewater treatment plant containing aminoglycosides, spiramycin and fluoroquinolones antibiotics. PMID- 26672202 TI - [Determination of 49 drugs and 5 metabolites in drinking water samples using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry]. AB - A method for the determination of 54 drugs in drinking water samples was developed by using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS). The target drugs in drinking water samples were enriched and cleaned-up by HLB solid-phase extraction (SPE) cartridges and then eluted with 5 mL methanol. The elute was collected, concentrated under a gentle stream of nitrogen gas, diluted with 0.4 mL 0.1% formic acid solution, and analyzed by UPLC-ESI MS/MS. The separation of the 54 drugs was performed on an ACQUITY UPLCTM BEH C18 column using mobile phases of 0.1% formic acid and methanol by gradient elution. The multiple reaction monitoring (MRM) mode was employed in mass spectrometry acquisition. The matrix matched external standard calibration was used for quantitation. The results showed that the average recoveries of the drugs in ground water, tap water and surface water were 58.7%-104.4%, 53.1%-109.5%, and 50.7%-118.8%, respectively, and the corresponding relative standard deviations (RSD, n=6) were 0.3%-12.8%, 1.0%-15.5%, and 0.4%-19.3%, respectively. The method quantification limits (MQL) for target compounds were in the range of 0.002-5.000 ng/L. The developed method was applied to analyze the water samples from Beijing. The results showed that 26 drugs were detected in ground water samples. PMID- 26672203 TI - [Simultaneous determination of 13 organic pollutants in water samples by high performance liquid chromatography-tandem mass spectrometry]. AB - On the basis of environmental quality standards for surface water, a sensitive and simple method was developed for the simultaneous determination of 13 organic pollutants, including dimethoate, dichlorvos, trichlorfon, parathion, methyl parathion, malathion, demeton, acrylamide, aniline, benzidine, carbaryl, Microcystin-LR and atrazine in water samples by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with direct injection. The water samples were filtered through 0.22 MUm of microfiltration membrane. With methanol-0.01% formic acid as mobile phase, the separation was performed on a Kromasil 100-5 C18 column (150 mm x 2.1 mm, 5 MUm) in gradient elution. The flow rate was 0.5 mL/min. The column temperature was 40 degrees C. The samples were detected by multiple reaction monitoring (MRM) mode with positive electro spray ionization. The organic pollutants were quantified by external standard method. The calibration curves of the organic pollutants show good linearity in suitable ranges with correlation coefficients (r) over 0.9995. The detection limits of organic pollutants in samples ranged from 0.02 MUg/L to 0.1 MUg/L. The relative standard deviations of organic pollutants were 0.5%-5.0% (n= 6). The average recoveries of the 13 organic pollutants spiked in water samples ranged from 81.2% to 112%. The method has been proven to be sensitive, rapid and with little interference. It is suitable for the determination of the 13 organic pollutants simultaneously in the surface and underground waters. PMID- 26672204 TI - [Determination of 12 flavonoids in tobacco leaves using ultra-high performance liquid chromatography-tandem mass spectrometry]. AB - Flavonoids are very important secondary metabolites for tobacco plants. They are also considered as important flavor precursors for cigarettes. A method of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of 12 flavonoids in tobacco leaves. The developed method determined 10 more flavonoids compared to the traditional method. A solution of methanol-water-chloroform (5:2:2, v/v/v) was used to extract the flavonoids from tobacco leaves and remove the pigment. Instrument analysis using the UPLC-MS/MS was completed in 13 min. The method validation was performed, and the results showed that the linear correlation coefficients (r2) of all the 12 flavonoids were more than 0.99. The limits of detection and the limits of quantification were in the range of 0.3-100 MUg/L and 1.2-400 MUg/L, respectively. Intra-day and Inter-day reproducibilities were in the range of 3.5%-7.4% and 5.2%-11.4%, respectively. The recoveries were 81.2% 111.9%. The established method was successfully used to analyze the flavonoids of tobacco leaves of 11 varieties. Significant concentration differences of the flavonoids were found among the determined varieties. Furthermore, significant positive correlation among the flavonoids with similar chemical structures (aglycones and their related glycosides, glycosides with the same aglycone, and similar aglycones) was found using the acquired data. PMID- 26672205 TI - [Determination of five triazine herbicides in infant milk powder by high performance liquid chromatography coupled with ionic liquid-based homogeneous liquid-liquid microextraction]. AB - A high performance liquid chromatography coupled with homogeneous liquid-liquid microextraction was developed for the determination of five triazine herbicides in infant milk powders. The ionic liquid was used as microextraction solvent. The separation of the herbicides was performed on an Eclipse XDB-C18 column using acetonitrile and water as mobile phases in gradient mode. The effects of homogeneous liquid-liquid extraction conditions on the experimental results were investigated in detail. Under the optimized experimental conditions, the calibration curves for determining the analytes were linear and the correlation coefficients were >= 0.9992. The limits of detection for cyanazine, desmetryn, terbumeton, terbuthylazine and dimethametryn were 12.1, 13.8, 11.8, 14.6 and 13.7 MUg/kg, respectively. The recoveries of the analytes spiked in four infant milk powders ranged from 92.2% to 103.2% and the relative standard deviations were lower than 6%. This method is sensitive, simple, and suitable for the determination of triazine herbicides in milk powder samples. PMID- 26672206 TI - [Ion-pair chromatography-indirect ultraviolet detection for determination of tetraethyl ammonium using a monolithic column and a packed column]. AB - Two methods were developed for the determination of tetraethyl ammonium by ion pair chromatography-indirect ultraviolet detection using a monolithic column and a packed column with ionic liquid as additive in mobile phase. Chromatographic separations were performed on a monolithic column and a packed column both on reversed phase using imidazolium ionic liquid aqueous solution-ion-pair reagent organic solvent as mobile phase. The effects of the background ultraviolet absorption reagent, detection wavelength, ion-pair reagent, organic solvent, column temperature and flow rate on the determination of tetraethyl ammonium were investigated. The difference between the two chromatographic columns was compared and the retention rules were discussed. Under the optimized chromatographic conditions, for tetraethyl ammonium on monolithic column and packed column, the retention times were 2.40 and 3.02 min; the detection limits (S/N=3), 0.04 and 0.07 mg/L; the RSDs (n = 5) for peak areas, 0.16% and 0.11%; and the RSDs (n=5) for retention times, 0.02% and 0.01%, respectively. The two methods have been successfully applied to the determination of tetraethyl ammonium ionic liquids synthesized by laboratory. The recoveries of the tetraethyl ammonium after spiking were 98.2% and 99.1%, respectively. The two methods can meet the requirements for the quantitative analysis of tetraethyl ammonium. PMID- 26672207 TI - A novel liquid chromatographic method with fluorescence detection for quantitation of tadalafil and dapoxetine hydrochloride in pharmaceutical dosage form and human plasma. AB - Tadalafil (TAD) and dapoxetine HCl (DAP) are recently co-formulated and both show native fluorescence. Therefore, a novel, accurate, specific and sensitive reversed-phase high performance liquid chromatographic method with fluorescence detection was developed and validated for their separation and quantitation in dosage form and human plasma using avanafil as an internal standard (IS). Separation was achieved using isocratic elution within 7.0 min on C18 column and acetonitrile-0.15% triethylamine (40:60, v/v; pH 4) as a mobile phase. The flow rate was 1.0 mL/min and the detection was time-programmed at 330, 410 and 370 nm for TAD, DAP and IS, respectively, after excitation at 236 nm. The linear ranges from 0.01 to 30.00 MUg/mL for each drug with the limits of detection of 4.20 and 7.20 ng/mL for TAD and DAP, respectively. The method was validated in accordance to the International Conference on Harmonization (ICH) guidelines and was successfully applied to spiked human plasma with mean recoveries of 98.17% and 98.83% for TAD and DAP respectively. PMID- 26672208 TI - [Determination of the contents of vitamin C and its derivatives in cosmetics by high performance liquid chromatography]. AB - A method has established for the detection of vitamin C (VC) and its derivatives (ascorbyl glucoside, AA-2G; magnesium ascorbyl phosphate, AA-2P; ascorbic acid ethyl ether, Only VCE) in cosmetics by high performance liquid chromatography (HPLC). Low fat cosmetic samples such as make-up water and lotion were extracted directly with 30 mL 0.02 mol/L potassium dihydrogen phosphate solution (pH 3.0). High fat cosmetic samples such as face cream and gel were well dispersed with 1.0 mL dichloromethane first, then extracted with 25 mL 0.02 mol/L potassium dihydrogen phosphate solution (pH 3.0). The sample solution was centrifuged with a speed of 12,000 r/min, then filtered through a 0.22 MUm syringe filter. The filtrate was analyzed on a column of YMC-Triart C18 (250 mm x 4.6 mm, 5 MUm) using 0.02 mol/L potassium dihydrogen phosphate solution (pH 3.0) and methanol as mobile phases with a flow rate of 1.0 mL/min. The temperature of the column was 25 degrees C and the detection wavelength was 250 nm. The standard working curves of the four analytes had good linear relationship (r2>0.9999). The detection limits of the four analytes were 0.04-0.08 g/kg (S/N=10). The recoveries were 95.6%-101.0% with the relative standard deviations of 0.62%-3.0% at the spiked levels of 0.25-5.0 g/kg. This method is a simple, rapid, exact and reliable for the determination of the contents of vitamin C and its derivatives in cosmetics. PMID- 26672209 TI - [Analysis of alkaline CuO degradation products of acid detergent fiber from tobacco leaves by using liquid chromatography]. AB - The acid detergent fiber (ADF) from tobacco leaves was obtained by treating the sample with petroleum ether-ethanol (6:4, v/v), 30 g/L sodium dodecylsulfate and 0.5 mol/L sulphuric acid containing 20 g/L hexadecyl trimethyl ammonium bromide successively. The ADF was degraded by the alkaline CuO oxidation procedure. In this work, six samples of ADF degradation products from tobacco leaves were prepared. The samples were analyzed by using gradient liquid chromatography (LC) where an Ultimate XB C18 column was used as stationary phase, with a mixture of methanol and water as mobile phase, at a column temperature of 35 degrees C and a flow rate of 0.8 mL/min. Dual wavelengths of 280 nm and 320 nm were chosen for the detection. It was found that there were four characteristic peaks for the ADF degradation products. By taking these peaks as research object, the optimum time for the degradation was found to be 5 h and the sample solution could be kept stable within 7 days. The established method may provide a new approach for the studies of the differences between lignin composition in different tobacco leaves and the relationship between lignin content and the smoking quality of tobacco leaves. PMID- 26672210 TI - [Genetic Polymophism and Evolution of SRPN14 Gene in Anopheles sinensis (Diptera : Culicidae)]. AB - OBJECTIVE: To identify and locate the serine protease inhibitor 14 (SRPN14) gene of Anopheles sinensis, and analyze its genetic polymorphism among populations as well as the selective pressure during evolution. METHODS: Primers were designed based on the genomic sequencing data of An. sinensis, and PCR amplification system for the SRPN14 gene was established. The chromosomal location of SRPN14 gene was determined by fluorescence in situ hybridization. The SRPN14 gene of An. sinensis populations collected from 18 sampling sites in 12 provinces (municipality) was sequenced, its genetic variations within and among populations calculated, and the selective pressure during adaptive evolution evaluated. RESULTS: The amplified part of the SRPN14 gene of An. sinensis was 429 bp in length, and had 77%(nt) and 88% (aa)similarities with An. gambiae. The SRPN14 gene located on 2L: 23C of salivary gland chromosomes of An. sinensis. The sequences of 411 individuals from 13 An. sinensis populations were analyzed. In the 411 individuals, the total number of alleles of the SRPN14 gene was 204, among which 51 (25.00% ) showed inter-population consistency. The ranges of SRPN14 allel number and genetic polymorphism were from 11 (Liaoning) to 33 (Chongqing), and from 0.008 (Liaoning) to 0.024 (Hainan), respectively. AMOVA result showed that genetic divergence within populations was significantly higher than that among populations; variation within populations was 95.79% of the total variation. The genetic divergence among populations was small, with FST value of 0.042. The number of synonymous substitutions in SRPN14 was significantly higher than that of non-synonymous substitutions sites, and omega was less than 1 in all populations. CONCLUSION: Genetic polymorphism occurs in SRPN14 gene of An. sinensis populations, and its evolution is under the negative selective pressure. PMID- 26672211 TI - [Analysis of MSP1 Allelotypes in Imported Cases of Plasmodium falciparum Malaria from Africa]. AB - OBJECTIVE: To understand the allelotype characteristics of the merozoite surface protein 1 (MSP1) in imported Plasmodium falciparum. METHODS: Blood samples were collected from P. falciparum-infected patients returning from African malaria endemic areas. Nested PCR was used to amplify gene fragments of MSP1 coding for block 2 and block 3 motifs of MSP1 of P. falciparum by using the MSP1-specific primers. Then the allelotype of MSPI was analyzed. RESULTS: The MSP1 allelotype was detected in 117 of 135 blood samples, with a detection rate of 86.7%. In the 117 cases with successful PCR amplification, the detection rates for MAD20, K1, RO33, MAD20+K1, MAD20+RO33, K1+RO33 and MAD20+K1+R033 were 6.0%(7/117), 36.8%(43/117), 20.5%(24/117), 6.8% (8/117), 3.4% (4/117), 17.1% (20/117) and 9.4% (11/117), respectively, wherein the mixed infection accounted for 36.8%(43/135). The mean multiplicity of infection(MOI) of MSP1 allelotype was 1.46. There was no significant difference in the proportion of patients with major severity of illness among the MAD20, K1 and RO33 genotypes. The proportions of patients with major severity of illness were 25.7%(19/74) and 32.6%(14/43) in 74 cases of singular infection and 43 cases of mixed infection, respectively. The two infection types of patients had 241 +/- 176 days and 285 +/- 216 days of stay abroad, with no significant difference between them. CONCLUSION: The three genotypes of MSP1 and their four types of combination exist in imported cases of P. falciparum malaria from Africa. K1 and RO33 are the dominant genotves. PMID- 26672213 TI - [Clinical Analysis of 36 Elderly Patients with Schistosome-Induced Liver Disease Complicated by Hepatitis E]. AB - OBJECTIVE: To explore the clinical characteristics of schistosome-induced liver disease complicated by hepatitis E in elderly patients. METHODS: Thirty-six senile patients with schistosome-induced liver disease complicated by hepatitis E (the observation group) and 38 senile patients with simple hepatitis E (the control group) were from the First Hospital of Jiaxing City. The blood routine measurements, indicators of liver function and blood coagulation function, serum markers of liver fibrosis, and B-ultrasonic measurements of hepatic portal vein diameter and spleen hilus inside diameter of splenic vein, were analyzed in combination with clinical manifestations, disease course and outcomes. RESULTS: All the 74 cases had acute onset of hepatitis E. The patients in the observation group had severer conditions, which were prone for aggravation. In this group, the incidences of nausea (91.7%, 33/36), vomit (88.9%, 32/36) and pruritus (33.3%, 12/36) were all higher than those in the control group (P<0.05). The levels of average total bilirubin and alanine aminotransferase at admission were (153.22+/-29.71) mol/L and (705.14+/-356.55) U/L respectively, in the observation group, significantly higher than those in the control group [(109.89+/-26.28) mol/L and (485.74+/-297.49) U/L](P<0.01). In contrast, the levels of albumin, prothrombin activity, white blood cell, hemoglobin and platelet at admission were significantly lower in the observation group than in the control (P<0.01). In addition, the levels of four serum markers of liver fibrosis, i.e, the transparent hyaluronic acid, laminin, type III serum procollagen peptide and type IV collagen, were all significantly higher in the observation group than in the control (P <0.01). Further, B-ultrasonic measurements of hepatic portal vein diameter and spleen hilus inside diameter of splenic vein in the observation group were (16.56+/-3.38) mm and (10.28+/-3.31) mm, significantly higher than those in the control[(14.82+/-3.48) mm and (8.26+/-3.27) mm]. The recovery of liver function in the observation group was largely prolonged compared with the control [hospitalization duration, (43.7+/-7.1) days versus (29.5+/-5.1) days, P<0.01]. CONCLUSION: The elderly patients with schistosome-induced liver disease complicated by hepatitis E show severer liver injury than those with pure hepatitis E, thus needing intensive care and treatment. PMID- 26672212 TI - [Preliminary Genetic and Functional Analyses of Schistosoma japonicum Chymotrypsin-like Protease]. AB - OBJECTIVE: To investigate the gene expression, localization and potential functions of Schistosoma japonicum chymotrypsin-like protease (SjCTRL) in the host, and evaluate its potential immune-protection efficacy against S. japonicum infection in mice. METHODS: The physicochemical properties of SjCTRL and its phylogenetic relationship with homologous genes from other species were analyzed with bioinformatic software. The distribution of SjCTRL transcripts in 26-day-old worms was investigated using whole-mount in situ hybridization. The transcriptional levels of SjCTRL in male and female worms at four development stages (14, 18, 22, and 26 days after infection) were measured with quantitative real-time PCR. The SjCTRL-dsRNA was prepared and used to induce RNA interference (RNAi) in 26-day-old worms via soaking in vitro, and confocal microscopy was used to observe the morphological changes of worms after RNAi. Primers were designed to amplify the encoding sequence (excluding the transmembrane region) from the S. japonicum cDNA. The truncated gene was subcloned into the pET-28a plasmid, transformed into E. coli BL21 (DE3) for expression. Mice were immunized with the purified recombinant protein and challenged with cercariae. The worms and mouse liver were collected on day 35 after the challenge, and the worm-reduction rate and egg-reduction rate were calculated. RESULTS: The in situ hybridization results showed that SjCTRL mRNA was located in the posterior segment of intestinal tract of female worms, and having abundence only in 26-day-old female worms. After RNAi with SjCTRL-dsRNA, the mRNA expression was reduced to 25.7% (P< 0.05), without significant morphological changes. Using the recombinant plasmid pET-28a/SjCTRL, expression of insoluble SjCTRL protein was induced. Mice immunized with this protein gained a worm-reduction rate of 25.4% and an egg reduction rate of 80.5% in liver after being challenged with cercariae. CONCLUSION: This study proves a high transcriptional level of SjCTRL in the posterior segment of intestinal tract in 26-day-old female worms, which can be reduced by RNAi treatment in vitro. Immunization with the SjCTRL protein can reduce adult worms and liver eggs. PMID- 26672214 TI - [Survey on Malaria Epidemics in China-Myanmar Border Area]. AB - The malaria epidemics in Laza city of Myanmar and Yingjiang county in Yunnan province of China in 2012 and 2013 was reviewed retrospectively, and a survey on malaria infection was conducted in residents in the border areas. A total of 179 malaria cases were reported in Yingjiang county from 2012 to 2013, with an average annual incidence of 2.9 per 10,000. Of the 179 cases, 77.7% were imported cases and 22.3% were local cases; 79.3% were infected with Plasmodium vivax, 20.1% with P. falciparum, and 0.6% unidentified. In Laza city of Myanmar, 2,069 malaria cases were reported, with an average annual incidence of 322.5 per 10,000. Of them, 73.4% cases were infected with P. vivax, 20.1% with P. falciparum and 6.5% unidentified. In addition, the microscopic results revealed that the malaria parasite rate in the residents in Yingjiang county was 0%, while that in Laza city was 1.5%. PMID- 26672215 TI - [Cloning and Prokaryotic Expression of Fusion Gene of Group II Allergen Der p2 T Cell Epitope from Dermatophagoides pteronyssinus]. AB - OBJECTIVE: To express and purify the T cell epitope fusion peptide of the major allergen Der p2 from Dermatophagoides pteronyssinus. METHODS: Nucleotide sequences reported to encode four T-cell epitopes (T1-T4) of Der p2 of D. pteronyssinus were linked in the rank of T1-T2-T3-T4. In this way, the chimeric gene was synthesized, named as Der p2 T. The gene of Der p2 T was amplified by PCR, purified, and cloned into the pET-28a (+) vector, forming the prokaryotic recombinant expression vector pET-28a (+)-Der p2 T. This formation was verified by double digestion. The pET-28a (+)-Der p2 T vector was transfected into E. coli strain BL-21, and its expression was induced by addition of IPTG. The recombinant protein was purified and collected by Ni-NTA affinity chromatography, and prepared for SDS-PAGE and Western blotting analysis. ELISA was used to evaluate the binding ability of Der p2 T cell epitope fusion peptide to serum IgE from patients with house dust mite allergy. RESULTS: Double digestion results confirmed the construction of the pET-28a (+)-Der p2 T vector. SDS-PAGE revealed the expression of recombinant Der p2 T cell epitope fusion peptide with M, of 10,000. Western blotting confirmed the purification of Der p2 T cell epitope fusion peptide. The binding ability of Der p2 T cell epitope fusion peptide to serum IgE from patients with house dust mite allergy [(37.70+/-9.89) ug/ml] decreased significantly in comparison to that of Der p2 [(85.89+/-9.63) ug/ml] (P<0.01). CONCLUSION: The Der p2 T cell epitope fusion peptide is prepared, and its binding ability to serum IgE from patients with house dust mite allergy significantly decreases than that of Der p2. PMID- 26672216 TI - [Survey on Echinococcosis in Maqing County of Qinghai Province]. AB - OBJECTIVE: To understand the status of echinococcosis in Maqing County of Qinghai Province in order to facilitate echinococcosis control in this region. METHODS: Ultrasonic scanning and indirect hemagglutination assay were used to detect echinococcosis infection in residents >1 year old, according to the People's Republic of China Health Industry Standard--Diagnostic Criteria for Hydatid Disease (WS257-2006). Meanwhile, ELISA was used o detect the Echinococcus antigen in dog's feces collected in Youyun, Dangluo and Xiadawu townships. RESULTS: Ultrasonic scanning showed that the prevalence of hydatid disease in the residents was 7.4% (116/1 561), cystic hydatid disease 5.3% (82/1 561), alveolar hydatid disease 2.2% (34/1 561). The serum positive rate in human population was 23.8%(307/1 288). Of the 82 cases of cystic hydatid disease, 23 cases (28.1%) had the hydatid cyst with a diameter of >10 cm. The prevalence in males and females in the county was 5.3% (40/753) and 9.4% (76/808), respectively (P<0.05). Among populations with different occupations, the highest prevalence of hydatid disease fell into houseworkers (11/61, 18.0%), monks (5/41, 12.2%) and herdsmen (84/758, 11.1%). Among the age groups, the groups of >60 years (24/132, 18.2%) and 30-40 years (31/302, 10.3%) had higher prevalence of hydatid disease. The three townships with the higher prevalence were Youyun (29/247, 11.7%), Changmahe (6/63, 9.5%) and Dangluo (54/645, 8.4%). Of the 199 samples of dog's feces, 54 were positive for Echinococcus antigens (27.1%), with a positive rate of 40.4% (23/57) in Youyun towship, being significantly higher than in the other two (P<0.05). CONCLUSION: Maqin county is a co-endemic area of cystic echinococcosis and alveolar echinococcosis. The prevalence is higher in females and those over 60 years-old. PMID- 26672217 TI - [Preliminary Analysis of the Genetic Loci of SAG1 and SAG3, the Surface Antigens of Toxoplasma gondii, in HIV-positive People in Dali of Yunnan Province]. AB - OBJECTIVE: To identify the genotypes of Toxoplasma gondii that infects HIV positive people in Dali of Yunnan Province through analyzing the genetic loci of the surface antigens SAG1 and SAG3. METHODS: A total of 291 blood samples from HIV-positive cases were collected from the HIV/AIDS Prevention and Control Institution in Yunnan. Nested PCR was used to amplify SAGI and SAG3 genes in the blood samples. The products were digested with restriction enzymes Sau96 I, Hae II and Nci I, and sequenced. RESULTS: Of the 291 HIV-positive blood samples, 64 showed successful amplification of SAGI gene, and 42 of SAG3 gene, with product sizes of 390 bp and 225 bp, respectively. Enzymetic digestion of the PCR products resulted in fragments of 350 bp and 50 bp for SAGI, and -200 bp band for SAG3, consistent with RH, a particular type I strain of T. gondii. Sequencing of the SAG1 and SAG3 PCR products showed that their sequence identities with SAGI (Accession No. GQ253073) and SAG3 (Accession No. JX218225.1) of the type I strain of T. gondii were 99.98%-100% and 99.96% -99.98% respectively. CONCLUSION: The Toxoplasma gondii in HIV-positive cases in Dali of Yunnan Province is the type I strain of T. gondii. PMID- 26672218 TI - [Identification of Trypanosoma Species in Rattus flavipectus and R. losea using Microscopy and PCR Method]. AB - OBJECTIVE: To identify two suspected Trypanosoma species in Rattus found in Zhejiang Province using microscopy and PCR method. METHODS: Blood samples were collected from Rattus losea and R. flavipectus. Blood smears were prepared, and observed under microscope. The morphological indices of trypanosomes were measured and calculated. The genomic DNA was extracted from the trypanosomes, and the specific fragment of Trypanosoma 18S rRNA gene was amplified using PCR. The products were further sequenced and submitted to GenBank. Blast analysis was performed on line in NCBI. RESULTS: Blood samples from Ratts flavipectus and R. losea were collected from Lucheng District and Wencheng County of Wenzhou, respectively. The parasites from R. losea and R. flavipectus were found to possess the characteristic features of Trypanosoma species, such as nucleus, free flagellum, and kinetoplast, etc. The body length was 27.50 um and 23.80 um, and the free flagellum length was 9.60 im and 9.20 jim, respectively. The nucleus index was 0.74 and 1.05, the kinetoplast Index was 1.40 and 1.57, respectively. Based on the morphological characteristics and host specificity, the parasites from R. losea and R. flavipectus were identified as Herpetosoma species, mainly found in rodents. The amplified products were about 700 bp by 18S rRNA gene PCR with the DNA isolated from the trypanosomes. The products were further sequenced, and the resulting sequences were submitted to GenBank with assession numbers of KP098535 (from R. losea) and KP098536 (from R. flavipectus). Blast analysis showed that KP098535 was completely homologous with the sequences from Herpetosoma subgenus (AY491765.1, AY491764.1, and AJ223568.1), and KP098536 was completely homologous with Trypanosoma lewisi (AB242273.1, AJ009156.1). CONCLUSION: The Trypanosoma species found from Rattus flavipectus is Trypanosoma lewisi, and the other one belongs to Herpetosoma subgenus, which may be named as Trypanosoma lewisi-like trypanosome. PMID- 26672219 TI - [Clustering Analysis of Hydatid Disease in Gansu Province]. AB - The prevalence of hydatid disease in human population and livestock, and the positive rate of echinococcal antigen in canine feces were analyzed with sample clustering method, according to the survey on hydatid disease in 72 counties in Gansu province in the database of the National Survey on Prevalence of Echinococcosis in 2012. The prevalence of hydatid disease in huma and livestock, and the positive rate of echinococcal antigen in canine feces were 0-1.59%, 0 15.22%, and 0-16.87% respectively. Clustering analysis revealed four types of prevalence in the 72 counties. The first type existed only in Dunhuang city, with the three indicators being 0.27%, 15.22% and 16.87%; the second in four counties, with the three indicators being 0.43%, 6.57% and 1.83%; the third in 22 counties, with the three indicators being 0.22%, 1.15% and 1035%; and the fourth in 45 counties, with the three indicators being 0.16%, 0.58% and 1.69%. PMID- 26672221 TI - [The mosquito name of Anopheles ramsayi in China should be corrected to Anopheles pseudojamesi Strickland and Chowdhury, 1927 (Diptera : Culicidae)]. AB - The present review deals with the nominate priority of mosquito names between An. ramsayi Covell, 1927 (published in Ind J Med Res, April 1927 number) and An. pseudojamesi Strickland and Chowdhury, 1927 (published in Ind Med Gaz, May 1927 number) and its synonymy reported in India. They adopted the priority by order of monthly number of the periodicals without exact dates. The name ranisayi for the priority used as the valid name long time in literature, and forms a wrong nominate case. The editor of Ind. Med. Gaz.(1936) entered an interesting footnote regarding the exact dates of publication for two names: ramsayi issued in May 15th 1927, while pseudojamesi was May 10th 1927. The fact showed that the name pseudojamesi has its priority. Nurul Huda and Harrison (1985) informed clearly for wrong nominate case, and clarified that the name pseudojamesi has priority over ramsayi. Therefore An. pseudojamesi is elevated to species rank (corrected to valid name), whereas An. ramsayi is regarded as its junior synonym (invalid name). That the rejected name of An. ramsayi now still being used in Chinese lliterature should he corrected to An. pseudojamesi quickly. PMID- 26672220 TI - [Prevalence of Neospora caninum Infection in the Intestine of Pet Dogs in Some Areas of Anhui and Zhejiang]. AB - OBJECTIVE: To investigate the prevalence of Neospora caninum infection in the intestine of pet dogs in areas of Anhui and Zhejiang. METHODS: A total of 315 fecal samples from pet dogs were collected in pet clinics from April to December 2013 in Baohe District in Hefei city, Xuanzhou District in Xuancheng city, Fengyang County in Chuzhou city, Longzihu District in Bengbu city, and Si County in Suzhou City in Anhui Province, as well as in Yuhang District in Hangzhou city of Zhejiang province. All samples underwent nested-PCR targeting Neospora specific gene NCLI-004830. The results were further confirmed by PCR amplification of N. caninum ITS1 followed by sequence analysis. RESULTS: The rate of N. caninum infection in the 315 samples was 1.59% (5/315). The infection rate in Chuzhou and Bengbu was 3.37% and 6.45%, respectively, and no N. caninum infection was found in the remaining areas. There was no association between the infection rate and the sex or age of the dogs. CONCLUSION: N. caninum infection is prevalent in pet dogs in Chuzhou and Bengbu of Anhui. PMID- 26672222 TI - [The Role of Adoptive Transfer of Immune Cells in Helminth- induced Regulation of Allergy and Autoimmune Diseases]. AB - Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases. PMID- 26672223 TI - [Cloning and Bioinformatics Analysis of Toxoplasma gondii ROP21 Gene]. AB - The full-length gene sequence of Toxoplasma gondii ROP21 (TgROP21) gene was amplified with PCR. The signaling peptide and transmembrane domain of TgROP21 protein were predicted by SignaIP and TMHMM online predictive sites, and the hydrophilicity and antigenic index of this protein were ananlyzed with DNAStar software. Meanwhile, the functional domains and tertiary structure were modeled by combined use of ExPASY and PRODATA online sites. As expected, the PCR results revealed one band at 2,022 bp. The signaling peptide, transmembrane domain, hydrophilicity, antigen index, functional domain and 3D structure of TgROP21 were successfully predicted. This work may provide a theoretical foundation for further verification of TgROP21 function. PMID- 26672224 TI - [Research Advances on Toxoplasma gondii Virulence Mediating Factors]. AB - Toxoplasma gondii strains are grouped into three clonal lineages (Types I, II , and III) with different virulence. T. gondii rhoptry proteins ROP18, ROP16, and ROP5 are the major virulence factors, which are secreted into the host cell by T. gondii during invasion and mediate the strain virulence. This paper reviews the research progress of T. gondii virulence mediating factors. PMID- 26672225 TI - [Preliminary Evaluation of Potential Transmission Risk of Malaria after Earthquake in Cangyuan County, Yunnan Province]. AB - OBJECTIVE: To evaluate the transmission risk and the prevalence potential of malaria in Cangyuan ounty after earthquake. METHODS: The malaria epidemiological data were collected through the web-based reporting system and the malaria statistics annual reporting system from 2005 to April 2015, and the epidemic factors of nalaria after earthquake in the recent three years in Cangyuan County of Yunnan Province were analyzed. RESULTS: according to the web-based reporting system, 799 malaria cases were reported in Cangyuan County from 2005 to April 2015, of which 652 w6re vivax malaria, 127 falciparum malaria, and 20 unclassified. The highest number of cases occurred in 2006 (n=326), and one indigenous falciparum malaria case was reported after earchquake. In iddition, the cases were mainly distributed in Mangka (n=320, 40.1%), Banlao (n=191, 23.9%), Banhong (n=98, 12.3%) and Mengdong (n=92, 11.5%). According to the annual reporting system, there were a total of 519 ndigenous cases (58.4%) and 370 imported cases (41.6%) from 2005 to April 2015. The proportion of indigenous ,ase was above 65% in each year except for 2006, when it was less than 15%. The risk indicator in western ownships of Canyuan County was higher, especially in Mangka and Mengjiao. CONCLUSIONS: There is a potential isk of malaria transmission in Cangyuan County of Yunnan province, due to the huge natural, social and biological ilterations after earthquake and the yet presence of malaria transmission vehicle. PMID- 26672226 TI - [Four cases of trichiniasis in Lhasa, Tibet]. PMID- 26672227 TI - [Comparison of Malaria Diagnosis between County and Provincial Laboratories in Guizhou Province]. AB - Malaria cases reported by county laboratories were further tested in the provincial laboratory in Guizhou province by using PCR test and microscopy. The consistency between PCR and microscopic results in the provincial laboratory was set as the basis for evaluation of microscopic results in county laboratories. In 89 samples, 24 were identified by PCR to be positive for malaria, among which 15 were infected with P. falciparum, 7 with P. vivax, and 2 with P. ovale; all were imported cases. And 21 samples had consistent identifications by PCR test and microscopic examination in the provincial laboratory. The total coincidence rate between county and provincial laboratories was 79.8%(67/84), and the undetected and error rates in county laboratories were 9.5%(2/21) and 23.8% (15/63), respectively. The Kappa value between county and provicial diagnosis was 0.6, being at the medium-to-high level of consistency. PMID- 26672228 TI - [Analysis of Time Distribution of Malaria Incidence in Baoshan City During 1990 2014]. AB - The malaria epidemic data in Baoshan city from 1990 to 2014 were analyzed with concentration ratio and circular distribution. Results showed that the incidence of malaria in Baoshan city displayed a trend of decrease from 1990 to 2014. The total concentration ration M was 0.36, the circular distribution r was 0.30, and the average angle alpha was 148.78 degrees . The malaria incidence peaked on May 31, with the epidemic period being from March 2 to August 29, which is inconsistent with the seasonal ebb and flow of local malaria vector. PMID- 26672229 TI - [Infection of Mice with Normal Immune Function by Taenia asiatica]. AB - The Taenia asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min, 6 min and 8 mins were subcutaneously injected into mice with normal immune function(groups Al-A3 respectively, n=20 in each) and mice with immunosuppression (groups B1-B3, n=20 in each). All groups of mice began to show body discomfort on day 5 after infection and develop lumps on the back about on day 15. In groups Al A3, animal death occurred during days 7-15, with a same survival rate of 95.0%(19/20) and infection rate of 89.4%(17/19), 73.6%(14/19) and 47.3%(9/19) respectively. In groups B1-B3, animal death occurred during days 7-50, with survival rate of 60%(13/20), 55%(11/20)and 55%(11/20) and infection rate of 76.9% (10/13), 54.5% (6/11) and 45.4% (5/11) respectively. After the scolex of cysticercus was evaginated with 15% pig bile, four suckers, an apparent rostellum and two distinct hook-like puncta structures were seen. These results indicate that mice with normal immune function can be used as a replacement of immunosuppressive mice to establish a T. asiatica oncosphere infection model. In addition, the T. asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min have the strongest infection ability. PMID- 26672230 TI - [Inhibitory Effect of the Excretory/Scretory Proteins of Trichinella spiralis on Proliferation of Human Hepatocellular Carcinoma HepG2 Cell line]. AB - Human hepatocellular carcinoma HepG2 Cell line were cultured with different concentrations of excretory/secretory proteins from Trichinella spiralis, and MTT assay was used to evaluate the cell inhibition rate. After co-cultured with 300 ug/ml excretory/secretory proteins for 24 h, the HepG2 cells were observed under a fluorescence microscope with AO and EB staining. When co-cultured with 75 ug/ml excretory/secretory proteins for 24 h, the HepG2 cells were quantified by flow cytometry using Annexin V-FITC/PI stain, and the expression of cleaved-caspase 9 was detected by immunofluorescence assay. The proliferation of HepG2 cells was inhibited significantly by excretory/secretory proteins in a dosage dependant manner. Under fluorescence microscope, some HepG2 cells presented typical apoptotic morphologic changes and the cleaved-caspase 9 protein expression was higher than that of the control. The early and late apoptotic cells and necrotic ones occupied 17.9%, 7.3%, and 6.6%, respectively. PMID- 26672231 TI - [One case of Necator americanus infection found under gastroscope]. PMID- 26672232 TI - [The management of facial nerve tumors involving the internal auditory canal]. AB - OBJECTIVE: 10 summarize tne clinical features of the facial nerve tumors involving the internal auditory canal and promote the management of facial nerve tumor. METHOD: We retrospectively reviewed the clinical manifestations, the experiences of diagnosis and treatment of the facial nerve tumor involving the internal auditory canal. All these 5 cases were enrolled during January 2013 to Apr 2015. RESULT: Among the 5 cases, 3 cases were facial neurilemmoma and the others were facial neurofibroma. The main symptoms of facial nerve tumors involving the internal auditory canal most commonly were facial paralysis companied with hearing loss. All the patients accepted the surgical treatment with various approaches, 3 cases of translabyrinthine approach, 1 case of middle fossa approach, and 1 case of combination of translabyrinthine and transotic approach. Total tumor resection were achieved in all 5 cases. Facial-hypoglossal nerve anastomosis was performed in one case, another case was undergone great auricular nerve graft. CONCLUSION: Surgical intervention for patients with facial neuroma involving internal auditory canal should be considered when facial weakness has deteriorated to grade 4. The management should be based on the patient's hearing, facial nerve function, tumor size and invasive extension to select the appropriate surgical procedures. PMID- 26672233 TI - [Clinical analysis of tympanosclerosis: characteristics and treatment]. AB - OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical management of tympanosclerosis. METHOD: The data of 73 patients who underwent surgery for tympanosclerosis were retrospectively analyzed with respects to the clinical characteristics, diagnosis and management. RESULT: Seventy-three patients with tympanosclerosis (involving 73 ears) , including 17 patients with sclerosis of tympanic membrane (type I), 23 patients with fixed Malleus-incus complex (type II), 8 (type III) with fixed stapes, and 25 (type IV) with extensive typannosclerosis. Sclerosis was seen most frequently in the malleus, incus and attic, followed by the tympanic membrane, incudomalleolar joint and other regions. Audiometry was performed for all the patients 1 weeks before and 1 year( the least) after operation, which were (51.70 +/- 14.93)dB HL and (36.24 +/ 11.58) dB HL respectively, with success rate 83% (61/73). CONCLUSION: Most of the patients suffer from conductive hearing loss. Teatment of the sclerosis around stapes is a key point. Acording to the sites of lesion and hearing level, hearing structures should be reconstructed by the rules of tympanoplasty and stapes surgery. PMID- 26672234 TI - [Air-conducted ocular vestibular-evoked myogenic potential in patients with sudden sensorineural hearing loss]. AB - OBJECTIVE: To investigate the characteristics of air-conducted ocular vestibular evoked myogenic potential(oVEMP) in patients with sudden sensorineural hearing loss (SSHL). So as to understanding the range and the degree of the vestibular system damage in patients with SSHL. METHOD: Thirty-five cases of unilateral SSHL were enrolled as the observing group from December in 2013 to December in 2014. 500 Hz air-conducted tone burst was employed as stimulation. Fifity-five healthy young subjects were recruited as the control group. The results were compared between the affected ears, the contralateral ears and the normal controls. RESULT: Thirty-five patients with SSHL, 31 of them in both ears lead to oVEMP Waveform, 4 sick ears did not elicit oVEMP waveform, extraction rate of 88%. 95 dBHL air-conducted get the latencies of P1 and N1, P1-N1 interval, peak-to-peak P1-N1 amplitude in healthy ear were (11.92 +/- 0.85)ms; (17.07 +/- 1.04)ms, (5.15 +/- 0.69)ms, (5.44 +/- 2.53) uv. 95 dBHL air-conducted get the latencies of P1 and N1, P1-N1 interval, peak-to-peak P1-N1 amplitude in sick ear were (12.16 +/- 0.76) ms; (16.94 +/- 2.57)ms, (5.16 +/- 0.73)ms, (2.89 +/- 1.66) v. The 55 cases (110 ears) were elicited P1-N1 complex typical, extraction rate was 100%. The threshold of oVEMP examination was (82.23 +/- 2.92) dBHL, 95 dBHL air-conducted get the latencies of P1 and N1, P1-N1 interval, peak-to-peak P1-N1 amplitude in these healthy young people were (11.53 +/- 0.80)ms, (16.61 +/- 0.87) ms, (5.18 +/ 1.04) ms, (5.96 +/- 2.59) uv, there were no significant differences between the affected ears, the contralateral ears and the normal controls in the latencies P1 and N1, P1-N1 interval. The wave amplitude in SSHL were lower than the healthy ear and the healthy control group. CONCLUSION: Through the detection of oVEMP in patients with SSHL,we observed that P1-N1 wave amplitude decreased, and it may be related to the damage of the utricle and vestibular nerve. PMID- 26672235 TI - [The clinical application of vestibular diagnosis and treatment system in benign paroxysmal positional vertigo]. AB - OBJECTIVE: To evaluate the effect of the vestibular diagnosis and treatment system (SRM-IV ) in diagnosis and treatment of patients with benign paroxysmal positional vertigo (BPPV). METHOD: Patients who were diagnosed as BPPV by SRM-TV in the clinic of our hospital from November 2013 to October 2014 were retrospectively analyzed in this study. RESULT: Among 425 suspected cases, 230 BPPV-positive patients were diagnosed including 131 cases of posterior SC (57.0%), 95 cases of horizontal SC (41.3%) and 4 cases of more than two SC (1.7%). The cure rate by SRM-V was 94.6% and the effective rate was 100.0%. The relapsed occurred in 10 patients (4.8%), which contained 4 men and 6 women. CONCLUSION: SRM-V can realize 360 degrees reasonable repositioning procedure while Canalish reposition procedure cannot. SRM-V can improve both the corrective rate of diagnosis and the cure rate, especially for the patients who suffered from complex BPPV. PMID- 26672236 TI - [The expression and clinical significance of pepsin and pepsinogen in patients with otitis media with effusion]. AB - OBJECTIVE: To analyze the role and significance of pepsin and pepsinogen in the pathogenesis of OME in children. METHOD: Pediatric patients with otitis media aged 2-8 years who enrolled in our department of the hospital from May of 2012 to December of 2012 were set as experimental group (38 cases, 48 ears) which should be underwent tympanic membrane puncture/tube insertion. Meanwhile, pediatric patients waiting for cochlear implant without otitis media (10 ears), were set as control group. Middle ear lavage fluid and plasma samples from the two groups were collected and detected using enzyme-linked immune method for pepsin and pepsinogen. RESULT: The concentrations of pepsin and pepsinogen in the middle ear lavage fluid of OME group [(48.8 +/- 415.99) ng/ml and 676.32 +/- 336.71)ng/ml] were significantly higher than those in the control group [(8.20 +/- 4.59)ng/ml and (77.27 +/- 50.33) ng/ml] (P < 0.01). Meanwhile, the concentration of pepsinogen in the middle ear lavage of OME patients was significantly higher than that of plasma (P < 0.01). The concentration of pepsin in the middle ear lavage fluid from the dry ear subgroup was lower than those in the serum ear and mucous ear subgroups (P < 0.01), but there was no significant difference about concentrations of pepsinogen among the dry ear, serum ear and mucous ear subgroups (P > 0.05). CONCLUSION: Pepsin and pepsinogen in the middle ear cavity of OME patients maybe originated from laryngopharyngeal reflux (LPR), indicating that LPR is associated with the pathogenesis of OME in children. PMID- 26672237 TI - [The diagnosis applying effects of ocular vestibular evoked myogenic potentials in BBPV disease]. AB - OBJECTIVE: To investigate the diagnosis applying effects of ocular vestibular evoked myogenic potentials(oVEMP) in peripheral BPPV disease. METHOD: During September 2012 to January 2015, we selected 80 healthy people in our hospital medical center as the control group, choose the same period of primary benign paroxysmal positional vertigo as the observation group of 80 patients. Two groups were carried out fully functional auditory evoked potential analysis, determination of oVEMP and cervical vestibular evoked myogenic potentials (cVEMP) anomaly amplitude threshold, P1 latencies, N1 incubation period. RESULT: The cVEMP abnormal rate in the observation group was 28.8%, the oVEMP abnormal rate was 38.8%, while cVEMP and oVEMP abnormal rates in the control group was 1.3% and 2.5% respectively that compared to significant differences between the two groups (P < 0.05). The oVEMP test amplitude in the observation group was (5.98 +/- 2.15) uv, the N1 incubation period was (10.03 +/- 0.76)ms, while the control group were (4.09 +/- 2.11)uv and (11.67 +/- 0.78) ms that compared difference were statistically significant (P < 0.05). The cVEMP test amplitude in the observation group was (154.8 +/- 43.9)2 uv, while the control group was (180.49 +/- 45.34)uv, compared the difference was statistically significant (P < 0.05). CONCLUSION: Paroxysmal positional vertigo patients ocular vestibular evoked myogenic potentials abnormal rate is relatively high, the utricle dysfunction for more severe than the balloon can be the subject of an objective function of the ear stone judgment, judgment in favor of the disease. PMID- 26672238 TI - [39 cases of malignant tumors originated from external and middle ear]. AB - OBJECTIVE: To describe our experience in the clinical manifestation and treatment of malignant tumors of the external and middle ear. METHOD: The study reviewed 39 patients between 1994-2011 in our hospital, including 15 pinna tumors, 18 external canal tumors and 6 middle ear tumors. 23 males and 16 females were enrolled in this study. The mean age of patients at the time of surgery was 59. Radiotherapy or radiotherapy and chemotherapy were the only possible treatment in 6 cases. Thirty-three patients were treated surgically, and 9 patients also received radiotherapy after surgery. RESULT: All of the patients had been followed up over 3 years, except for 1 case of external canal and 1 case of middle ear tumor. The 3-year survival of pinna, external canal and middle ear tumors were 86.7%, 82.4% and 60.0% respectively. At the last follow up, the pinna tumors showed that the survival rate was 100% in T1, T2 and Tx stage, and 0% in T4 stage; the external canal tumors showed that the survival rate was 90% in T1 stage, and 66.7% in T2, T3 stage; the middle ear tumors showed that the survival rate was 100% in T1 and T2 stage, 0% in T3 stage. CONCLUSION: The T staging system is for an important prognostic factor, and it is important for an early diagnosis and radical surgery to achieve a better therapeutical result. PMID- 26672239 TI - [Diagnosis value of thyroid imaging reporting and data system in thyroid nodules]. AB - OBJECTIVE: To explore the diagnostic value of the proposed thyroid imaging reporting and data system (TI-RADS) classification in thyroid nodules, and to investigate interobserver variability among different observers using TI-RADS classification for ultrasound. METHOD: We reviewed 667 thyroid nodules conventional ultrasound image data from 532 patients who were confirmed by Pathological diagnosis. Those ultrasound images were reviewed by 4 experienced sonographers who can independently assessed the sonographic characteristics and analyzed according to the TI-RADS classification. It is to assess the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the TI-RADS classification. The multirater kappa statistics were used to assess the interobserver agreement among different observers. RESULT: The overall sensitivity, specificity, negative predictive value (NPV) and Accuracy were 94%, 79%, 97% and 81%, respectively. Positive predictive values (PPVs) for categories 4 and 5 were 55% and 92%. There was substantial interobserver agreement for categories 3, 4B and 5 (Kappa = 0.62, 95% CI, 0.58-0.65), and was moderate agreement for category 4A (Kappa = 0.57) and 4B(Kappa = 0.60). CONCLUSION: The diagnostic criteria of TI-RADS for differentiating between benign and malignant thyroid nodules have a high diagnostic value. There was substantial interobserver agreement in different experienced sonographers. The TI-RADS diagnostic criteria have a high diagnostic value and has great practical value in making a proper and further treatment plan. PMID- 26672240 TI - [Differences in clinical features between cholesteatoma in external auditory meatus and middle ear]. AB - OBJECTIVE: Differences in clinical features, especially facial nerve canal leision between cholesteatoma in external auditory meatus and middle ear were compaired. METHOD: A retrospective clinical analysis was made. Clinical data included 125 cases of middle ear cholesteatoma with facial nerve canal leision and 28 cases of cholesteatoma occurred in external auditory canal from 2003-01 2014-08 in our hospital. RESULT: Clinical course of cholesteatoma in external auditory canal was 4.97 +/- 7.51 years, course of middle ear cholesteatoma was 16.60 +/- 14.42 years (P < 0.01). 21 cases (75%) of external auditory canal cholesteatoma were manifested as pneumatic mastoid and 110 cases (88%) of middle ear cholesteatoma were manifested as diploic mastoid respectively. 22 cases (78.6%) of facial nerve canal damage-in mastoid segment in cholesteatoma of external auditory meatus and 76 cases (60.8%) of facial nerve canal damage in tympanic segment in cholesteatoma of middle ear were observed (P < 0.01). The incidence rate of ossicular errosion in middle ear chol-esteatoma was significantly higher than that in external auditory meatus (P < 0.01). The incidence of semicircular canal defects in middle ear cholesteatoma (30.4%), was significantly higher when comparing to the incidence (10.7%) in cholesteatoma of external auditory meatus (P < 0.05). CONCLUSION: The site of facial nerve canal lesion in middle ear cholesteatoma and cholesteatoma of external auditory meatus were different. More attention should be paid before and during operation to avoid facial nerve injury, including physical examinations, especial otologic exams, radiological reading and careful operation. PMID- 26672241 TI - [The clinical application of data mining in laryngeal cancer]. AB - OBJECTIVE: To provide a basis for the prediction and early diagnosis of laryngeal cancer through data mining and analysis. METHOD: We constructed a laryngeal cancer data warehouse on Cache and combined IBM Cognos for on-line analytical processing. After building research data set, software Weka was used for feature selection and data mining. RESULT: Data warehouse of laryngeal cancer was structured and Laryngeal cancer data were multidimensional presented. It is possible to find the high relevant and potential characteristics associated with laryngeal cancer by integration and 2-phase feature subset of data mining to extract the larynx. CONCLUSION: Application of data mining technology could help clinicians to find potential clinical knowledge and make early diagnosis of laryngeal cancer. PMID- 26672242 TI - [Clinical features, levels of protein carbonyl in serum of obstrucitive sleep apnea syndrome with type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the prevalence, clinical feature and levels of protein carbonyl (PCO) in serum of type 2 diabetes mellitus combining obstrucitive sleep apnea syndrome (OSAHS). METHOD: Two hundred and three patients with type 2 diabetes were taken multi lead sleep detection and their AHI, age, height, body mass index (BMI),waistline, duration of diabetes, fast blood glucose, HbA1c level and level of PCO in serum were recorded. RESULT: The prevalence of OSAHS was 79.2% in 203 patients, serious apnea 30.4%, moderate apnea 45.4%, mild apnea 24.2%. BMI, waistline, fast blood glucose, HbA1c level and level of PCO in serum were higher in patients complicated with OSAHS (P < 0.01). HbA1c was independently and positively correlated with patients with OSAHS risk (P < 0.05, OR 6.11). The independent correlation factors of AHI included HbA1c level,BMI, waistline, duration of diabetes and level of PCO in serum,with HbA1c as the predominant factor (P < 0.05). CONCLUSION: The prevalence of OSAHS was higher in patients of type 2 diabetes mellitus combining (OSAHS). Moreover, in these patients poor glucose control and aggravated protein oxidative injury were observed. PMID- 26672243 TI - [Clinical comparison of idiopathic sudden deafness in children and the elderly]. AB - OBJECTIVE: This retrospective study compared clinical manifestations of idiopathic sudden hearing loss between children and the elderly. METHOD: 44 pediatric patients and 76 elderly patients diagnosed with idiopathic sudden deafness in our clinic from December 2009 to September 2014 were enrolled. Different clinical parameters were compared. RESULT: The incidence of initially profound hearing loss was highest and mild hearing loss was lowest in both groups (P < 0.05). There were no differences in the proportion with initially mild, moderate, severe, and profound hearing loss between both groups (P > 0.05). The number of patients was the most in initially profound type of audiogram pattern and the fewest in ascending type in both groups (P < 0.05). Hearing recovery rates in children (27/44, 61.4%) was higher than that in elderly patients (32/76, 42.1%) (P < 0.05). There were no differences in hearing recovery rates of the patients with initially level of hearing loss in both groups (P > 0.05). The highest recovery rate in children was in those with descending type and the lowest was in those with profound type (P < 0.05). There were no differences in hearing recovery rates in elderly patients with initially different types of audiogram pattern (P > 0.05). Hearing recovery rates of descending type in children were higher than that in elderly patients. Presence of tinnitus in pediatric patients was not relavent to the outcome (P > 0.05). Presence of tinnitus in elderly patients was associated with favorable outcomes. (P < 0.05). Presence of dizziness in pediatric patients was not relavent to the outcome (P > 0.05). Presence of dizziness in elderly patients was associated with poor outcomes (P < 0.05). Presence of initially different degrees of opposite side hearing loss in elderly patients was not relavent to the outcome (P > 0.05). Presence of chronic diseases in elderly patients was not associated with the outcome (P > 0.05). CONCLUSION: The clinical manifestion of idiopathic sudden deafness is respective in Children and in elderly patients. PMID- 26672244 TI - [Diagnosis and treatment of vocal process granuloma induced by gastroesophageal reflux: four cases report]. AB - OBJECTIVE: To explore the mechanism, clinical characterization, diagnosis and therapeutic approach of vocal process granuloma(VPG) induced by gastroesophageal reflux. METHOD: We performed a retrospective review of 4 cases. RESULT: In 4 male cases, 3 cases had no obvious symptoms of stomach and esophagus and 1 case had symptoms of bloating and acid reflux. Additionally, 4 cases in which lesions were all located to the left side were diagnosed by trial therapy with proton pump inhibitors (PPIs) with good responding. 2 of 4 cases were relapsed after operations. Meanwhile 4 patients were treated by Rabeprazole for acid suppression therapy and 3 cases were cured and 1 invalid case was cured by Pantoprazole. All patients were followed up for 4-48 months with no recurrence. CONCLUSION: Gastroesophageal reflux is an important pathogenic factor to the VPG. The majority of patients with VPG do not have gastroesophageal reflux symptoms. Besides, most lesions located in the left are associated with sleeping position. The diagnosis is mainly based on the laryngoscope examination and trial of acid suppression therapy. Moreover, recurrence risk is high-with simple operation in VPG therefore the main treatment is a antireflux and it is also valid by replacing byother PPI treatment. The treatment must be long enough. Meanwhile, the comprehensive treatment should be noticed. PMID- 26672245 TI - [Endoscopic anatomy study of jugular foramen region]. AB - OBJECTIVE: To observe anatomic structure of jugular foramen region by endoscope, to provide anatomic data for avoiding damnification in the surgery. METHOD: We performed the retrolabyrinthine and retrosigmoid endoscopic surgery on 8 fomalin fixed adult cadaver specimens and observed the structures of jugular foramen by endoscope and compared the different surgeries at the same time. We excised the calvarium and cereburm and exposured and observed the nerves and vessels. Moreover we measured the the distance from internal accoustic pore to glossopharyngeal and analyse the data by SPSS. RESULT: All retrolabyrinthine endoscopic surgeries were performed successfully. Only 4 postsigmoid endoscopic surgeries were performed without damage of cerebellum which is the major obstacles. The distance from internal accoustic pore to glossopharyngeal was(8.26 +/- 1.05) mm. About half of posterior inferior cerebellar arteries located to inboard of nerves. CONCLUSION: The jugular foramen region endoscopic surgery can be performed successfully by retrolabyrinthine. The "lockhole" technology by retrosigmoid is more difficult for blocking of cerebella. The internal acoustic porus is a fixed structure of the cerebellopontine angleand a perfect landmark to the surgery. PMID- 26672246 TI - [Stellate ganglion catheter retention with discontinuous block on efficacy and safety in the treatment of sudden deafness]. AB - OBJECTIVE: To investigate effect and safty evaluation of stellate ganglion catheter retention with discontinuous block on sudden deafness. METHOD: One hundred and twenty-six patiens with sudden monaural deafness were randomly divided into Catheterp and block and control groups with 42 cases in each group. All patients' throats were given conventional blood activating drugs, hormone and hyperbaric oxygen therapy. stellate ganglion puncture retained catheter were administrated to the patients in catheter group followed by ropivacaine block 1 times/day, block group stellate ganglion puncture and ropivacaine block 1 times/day. The patients in control group were only received routine comprehensive treatment. Patients in both catheter group and block groups were treated by hyperbaric oxygen therapy after the block treatment. Curative effects of three groups were observed. The patients' satisfaction, heart rate, the chages of blood pressure before and after the block, detachment of tubes, and adverse drug reaction were recorded. RESULT: The effect of the treatment in both catheter group, block group was better than in control group (85.7%, 37 cases); 83.3%, 35 cases) vs 64.3%, 27 cases, P < 0.05). The satisfactory rate in the patients in catheter group was significantly higher than block group (83.3%, 35 cases vs 61.9%, 26 cases, P < 0.05). The heart rate and the blood pressure before and 5 minutes after catheterization in catheter group and block groupwere changed obviously. Moreover, no adverse drug reaction and detachment of tubes were observed. CONCLUSION: It is a safe and effective administration of stellate ganglion catheter retention with interrupted ropivacaine block. PMID- 26672247 TI - [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats]. AB - OBJECTIVE: To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. METHOD: We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. RESULT: We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P < 0.05). In spiral ganglion cell plasm the expression of VIP and VIPR1 had no significant difference in three groups (P > 0.05). CONCLUSION: These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss. PMID- 26672248 TI - [Observation of mucosa of eustachian tube with scanning electron microscope on spontaneous otitis media in mice]. AB - OBJECTIVE: To investigate the ultrastructural changes of the mucosa of eustachian tube in mice and to reveals the influence of eustachian tube on middle ear function and its relavence with otitis media. METHOD: 12 wild type and 12 mutant mice were divided into two groups by age to observe the the ultrastructural changes of the mucosa of eustachian tube. RESULT: Wild type mice exhibited a thick lawn of morphologically normal, distributed cilia in the mucosa of the middle ear at both time points. The cilia of mucosa of middle ear in mutant mice were short, impaired and disrupted. The impairment of the cilia progressed to a much great severity at 6 months compared to 3 months. CONCLUSION: Otitis media occurs not only the ciliated cells decreased and the goblet cells increased. More importantly, the ciliary structure was damaged, leading to the dysfunction of the mucociliary transport system and causing otitis media. PMID- 26672249 TI - [Applications of improved micro-invasive percutaneous tracheostomy in the obese, severe patients of neurosurgery]. PMID- 26672250 TI - [Clinical analysis of external ear canal coating by otoendoscopy on otomycosis external with triamcinolone acetonide and econazole nitrate cream]. PMID- 26672251 TI - [Efficacy analysis of surgical procedures in patients with recurrent auricular pseudocyst]. PMID- 26672252 TI - [The clinical analysis of preschool children with large vestibular aqueduct syndrome]. PMID- 26672253 TI - [Congenital median dermoid fistula of nasal dorsum: one case report]. AB - Congenital median dermoid is an uncommon disease. Surgery is the main curative treatment. To review a clinical case and to summarise the characteristics and treatment experience of this disease, referring to the related literature, it is expected that we can provide more clinical thought and therapeutic method for congenital median dermoid fistula of nasal dorsum. PMID- 26672254 TI - [Aneurysmal bone cyst of the mastoid bone: one case report]. AB - Aneurysmal bone cyst of mastoid bone is seldom, here one case was reported. The mastoid bone of the patient presented with a baloon-like swelling full of non coagulated blood and serous-hemorrhagic fluid. CT scan demonstrated a large expansile destructive mass located in left mastoid bone region with the thin or absent cortical bone. The MRI demonstrated T2-weighted images and clear boudary from surrounding tissue. Pathologic reported that the mastoid bone was repalcement with lacunar divided by fibro-tissue, containing numerous hemosiderin, giant cells and inflammatory cells. A surgery was performed and the patient was cured. PMID- 26672255 TI - [Gastroesophageal reflux and otitis media with effusion]. AB - Otitis media with effusion (OME), a kind of inflammatory disease of the middle ear, is characterized by the retention of middle ear effusions and hearing loss. There are many factors involved in the development of OME including bacterial infection, formation of bacterial biofilms, eustachian tube dysfunction, adenoid hypertrophy, immune system disorders. Recently, some studies showed that gastroesophageal reflux has correlation with OME. PMID- 26672256 TI - [EAST/SeSAME syndrome and functional expression of inward rectifier potassium channel Kir4.1 in the inner ear]. AB - Inwardly rectifying potassium (Kir) channels exhibit an asymmetrical conductance at hyperpolarization (high conductance) compared to depolarization (low conductance). The KCNJ10 gene which encodes an inwardly rectifying K+ channel Kir4.1 subunit plays an essential role in the inner ear and hearing. Mutations or deficiency of KCNJ10 can cause hearing loss with epilepsy, ataxia, sensorineural deafness, and renal tubulopathy (EAST) or SeSAME (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance) syndromes. In this review, we mainly focus on the expression and function of Kir4.1 channels in the inner ear and mutation-induced EAST/SeSAME syndromes to provide insight for understanding the pathogenesis of deafness induced by KCNJ10 deficiency. PMID- 26672257 TI - [Successful prevention: communication or negotiation art?]. PMID- 26672258 TI - [Prevention: how can Switzerland make up the delay?]. AB - The quality of the Swiss health system is unanimously recognised, except as regards prevention. Within the OECD, our country is among those that invest the least in this area. Despite overwhelming evidence of its usefulness for public health, in autumn 2012 Parliament rejected the draft federal law on prevention and health promotion. Alain Berset, Federal Councillor in charge of Health since January 2012, provides insight into this ambiguous situation. PMID- 26672259 TI - [Swiss recommendations for the check-up in the doctor's office]. AB - Prevention and screening of diseases belong to the role of each primary care physician. Recommendations have been developed in the EviPrev programme, which brings together members of all five academic ambulatory general internal medicine centers in Switzerland (Lausanne, Bern, Geneva, Basel and Zurich). Several questions must be addressed before realising a prevention intervention: Do we have data demonstrating that early intervention or detection is effective? What are the efficacy and adverse effects of the intervention? What is the efficiency (cost-effectiveness) of the intervention? What are the patient's preferences concerning the intervention and its consequences? The recommendations aim at answering these questions independently, taking into account the Swiss context and integrating the patient's perspective in a shared decision-making encounter. PMID- 26672260 TI - [Screening and prevention of cognitive disorder in the elderly]. AB - Age is the main risk factor for dementia, and early stages of cognitive decline may be challenging to identify. In this review, potential benefits of early diagnostic assessment are discussed. These include the identification and timely treatment of potentially reversible causes for cognitive impairment, avoidance of potential deficits in treatment of medical comorbidities, the opportunity to plan better for future needs and, finally, the therapeutic potential of non pharmacological interventions. Furthermore, the promise of prospective disease modifying medications, which are currently still being tested in clinical trials, will be addressed. While regimens combining dietary changes and cognitive training, as well as physical exercise, have been shown to provide benefit at low risk for adverse effects, improved medical care for other age-related disorders such as arterial hypertension, cardiac disease or diabetes may also have significant impact on reducing dementia prevalence. PMID- 26672261 TI - [Depression...but which depression?]. AB - Despite intensive efforts in neurobiology and epidemiology, depression remains a diagnosis with blurred b. We illustrate this point by examining the controversial issue of systematic screening by GPs, which highlights tensions between psychiatry and general medicine. We suggest a broader perspective on depression, taking into account the patient's individuality, as well as potentially pathogenic social determinants. In the era of operational diagnostic criteria, clinical intuition and the wider sociological context of the doctor-patient relationship are relevant. PMID- 26672262 TI - [Doctor, I am having trouble breathing, an in-hospital point of view]. AB - Breathlessness is frequent in the hospital setting: almost 50% of seriously ill hospitalised patients complain of dyspnoea, and its presence aggravates morbidity and mortality. Evaluation of breathlessness, based on self-report, must be completed with the measurement of vital signs and with a search for clinical signs of serious problems - desaturation, stridor, use of accessory muscles or alteration of mental status - that need urgent treatment. After this first therapeutic step, the diagnostic strategy consists of a multidisciplihary approach to determine the physiopathological mechanisms of dyspnoea that will determinate its final management. PMID- 26672263 TI - ["Doctor, I am short of breath" - a primary care perspective]. AB - Breathing difficulty can be the first symptom of many diseases. Frequent causes of dyspnoea in patients under out-patient care are of pulmonary and cardiovascular origin. Deconditioning is often a contributing factor in patients with chronic lung or heart disease. Key elements in the evaluation of patients with chronic and acute dyspnoea will be reviewed in this article. PMID- 26672264 TI - [Shortness of breath: information for patients]. PMID- 26672265 TI - [Is prescription of a therapy costing 150,000 CHF reasonable?]. AB - The costs of medicinal products have increased substantially in the last decade. Access to medical innovations for all patients is in acute danger. This situation requires a political commitment by the wider community of caregivers, healthcare providers and industry. New pricing models are inevitable to garantee access to medical innovation for all people in our society. Further, we must require companies to be more transparent when setting drug prices and require an attitude of consensus on prices between these industries - financially sound. Finally, our health insurance system must accept some state control to avoid patient selection, but also know the precise margin of manoeuvre over time in terms of cost expenditures assigned to oncology. PMID- 26672266 TI - [Choosing Wisely: from theory to practice]. AB - "Choosing Wisely" is an innovative approach that the Network of Southern Switzerland Public Hospitals has decided to promote. Five standard diagnostic or therapeutic procedures have been chosen to explore the potential benefit of the "Choosing Wisely" initiative: the prescription of benzodiazepines, proton pump inhibitors or antibiotics on discharge from hospital, exposure to ionising radiation in radiological imaging and the number of blood samples taken during hospitalisation. As a first step we compared these variables in the medical and surgical departments of the four major public hospitals in Ticino. We observed significant and unexpected practical differences between specialties and between the different institutions. These results were presented to all concerned healthcare stakeholders. The next steps are to develop continuous monitoring of these indicators and specific recommendations by involving patients in the consciousness-raising process. PMID- 26672267 TI - [Sauna-goers live longer!]. AB - Sudden cardiac death (SCD) and death from cardiovascular disease are the most frequent causes of death in the general population. A new Finnish long-term study demonstrates that regular sauna bathing significantly reduces cardiovascular mortality - the more frequent and longer the more the benefit. This new insight creates new opportunities for primary prevention of SCD and cardiovascular death. PMID- 26672268 TI - [The Study about Spectrum Characteristic Analysis Method in the Induction Period of Gas Explosion Flame]. AB - Through analyzing the spectroscopic data of gas explosion flame whose volume fraction is 10% under a small scale experimental condition based on the target emission spectrum analysis methods; presents the gas explosion flame spectrum characteristic analysis methods about frequency domain feature parameters which include spectral density, band radiation light intensity, band average deviation, the time domain characteristic parameter which include band radiation energy, time average and deviation and the characteristic parameters which include skewness, kurtosis and half width; obtain the results that in the vicinity of somewhere, the spectral density converts between positive and negative in the range of 1 nm that the light intensity of gas explosion flame changes dramatically; the definite integral of gas explosion flame spectral waveband is strongest in the 550~900 nm; with the wavelength increases the detected time grow, the gas explosion flame spectral signal strength attenuation trends on the whole and after the peak interval appeared in the process of decay have weaken the strength of the enhanced; results show tha the target emission spectrum analysis methods can be applied to do the semi-quantitative analysis of dynamic process of gas explosion, the analysis spectral characteristics can be taken as a standard to detecting gas explosion flame. PMID- 26672269 TI - [Terahertz Absorption Spectra Simulation of Glutamine Based on Quantum-Chemical Calculation]. AB - With simulation of absorption spectra in THz region based on quantum-chemical calculation, the THz absorption features of target materials can be assigned with theoretical normal vibration modes. This is necessary for deeply understanding the origin of THz absorption spectra. The reliabilities of simulation results mainly depend on the initial structures and theoretical methods used throughout the calculation. In our study, we utilized THz-TDS to obtain the THz absorption spectrum of solid-state L-glutamine. Then three quantum-chemical calculation schemes with different initial structures commonly used in previous studies were proposed to study the inter-molecular interactions' contribution to the THz absorption of glutamine, containing monomer structure, dimer structure and crystal unit cell structure. After structure optimization and vibration modes' calculation based on density functional theory, the calculation results were converted to absorption spectra by Lorentzian line shape function for visual comparison with experimental spectra. The result of dimmer structure is better than monomer structure in number of absorption features while worse than crystal unit cell structure in position of absorption peaks. With the most reliable simulation result from crystal unit cell calculation, we successfully assigned all three experimental absorption peaks of glutamine ranged from 0.3 to 2.6 THz with overall vibration modes. Our study reveals that the crystal unit cell should be used as initial structure during theoretical simulation of solid-state samples' THz absorption spectrum which comprehensively considers not only the intra-molecular interactions but also inter-molecular interactions. PMID- 26672270 TI - [High-Sensitive Carbon Dioxide Detection Using Quartz-Enhanced Photoacoustic Spectroscopy with a 2.0 MUm Distributed Feedback Laser]. AB - A carbon dioxide (CO2) sensor is developed using quartz enhanced photoacoustic spectroscopy (QEPAS) with a 2.0 MUm distributed feedback diode laser. The detection is based on a 2f wavelength-modulation spectroscopy approach by dithering and scanning the laser current. The laser modulation depth is optimized at normal atmosphere pressure and room temperature. The influence of the H2O presence in the sample gas mixture on the CO2 sensor performance is also investigated. The results show that, with 1% CO2 concentration, the H2O in the concentration ranges of 0 to 0.2% has an effect on the CO2 signal amplitude and phase, and the largest amplitude difference is ~2.1 times. When the H2O concentration is over 0.2%, the CO2 signal amplitude is saturated and remains steady. Atmospheric CO2 concentration is well measured using the optimal sensor parameters. Benefiting from the strong absorption line intensity at 4989.97 cm( 1), a detection limit of 19 ppm (1sigma, 300 ms averaging time) is achieved, which corresponds to a normalized noise equivalent absorption coefficient of 4.71 * 10(-9) cm(-1) . W . Hz(-1/2). PMID- 26672271 TI - [A New Method of Accurately Extracting Spectral Values for Discrete Sampling Points]. AB - In the establishment of remote sensing information inversion model, the actual measured data of discrete sampling points and the corresponding spectrum data to pixels of remote sensing image, are used to establish the relation, thus to realize the goal of information retrieval. Accurate extraction of spectrum value is very important to establish the remote sensing inversion mode. Converting target spot layer to ROI (region of interest) and then saving the ROI as ASCII is one of the methods that researchers often used to extract the spectral values. Analyzing the coordinate and spectrum values extracted using original coordinate in ENVI, we found that the extracted and original coordinate were not inconsistent and part of spectrum values not belong to the pixel containing the sampling point. The inversion model based on the above information cannot really reflect relationship between the target properties and spectral values; so that the model is meaningless. We equally divided the pixel into four parts and summed up the law. It was found that only when the sampling points distributed in the upper left corner of pixels, the extracted values were correct. On the basis of the above methods, this paper systematically studied the principle of extraction target coordinate and spectral values, and summarized the rule. A new method for extracting spectral parameters of the pixel that sampling point located in the environment of ENVI software. Firstly, pixel sampling point coordinates for any of the four corner points were extracted by the sample points with original coordinate in ENVI. Secondly, the sampling points were judged in which partition of pixel by comparing the absolute values of difference longitude and latitude of the original and extraction coordinates. Lastly, all points were adjusted to the upper left corner of pixels by symmetry principle and spectrum values were extracted by the same way in the first step. The results indicated that the extracted spectrum values of all points were accurate. Experiment on OLI (Operational Land Imager), TM and ETM+ images showed that this method can accurately extract the discrete spectrum value, and as well, clear principle, simple and feasible operation, strong applicability, This paper provides a new idea for remote sensing image extraction of discrete point spectrum. PMID- 26672272 TI - [In Situ Infrared Spectroscopic Determination of Enzyme Activity]. AB - A real-time infrared (IR) spectroscopy measurement is an effective means to obtain enzymatic information either in vitro or in living cells, as it can provide direct, continue test of biomacromolecule reactions. The principles of measurements are performed basing on the fact that the absorption bands in spectra of reactants and products are usually separated to each other and changed independently with time. Therefore, it is possible to measure the enzymatic efficiency at any reaction time according to the changes of characteristic band, from either reactant or product. That is, IR spectroscopy can be used to obtain intracellular structural information during the cells metabolic processes, as which can provide detailed and reliable scientific evidences. In this paper, we summarized the new developments of IR spectra in the in vitro enzymatic assay for several representative enzymes, as well the screening of enzyme inhibitors, which was further extended to the identical aspect by using living cells as detection model. Such important enzymatic examination closes to the physiological conditions without labeling, supplying structural information of the related biomolecules. The developing trends of IR spectra are discussed and the perspectives of it in the research area are also provided in this review. PMID- 26672273 TI - [The Impacts of the Variation of Myanmar Jade Component on Its Infrared Spectroscopy]. AB - Myanmar jade is crystalline aggregate with the major mineral of jadeite. Jadeite can be represented by the crystal-chemical formula NaAlSi2O6. Isomorphous substitution occurs in the natural jadeite frequently, with replacement of Na by Ca, and replacement of Al by Mg, Fe, Cr etcetera, which makes the component of Myanmar jade much more complex and leads to the variation of its physical features, including color, transparency, refractive index, specific gravity and infrared spectrum characteristics, forming different types of Myanmar jade. The studies show that the vibrational spectra characteristics of the Myanmar jade varies depending on the substitution of different elements. In this work, we studied the impacts of the variation of Myanmar jade component on its infrared spectroscopy. 10 Myanmar jade samples which consisted of different chemical composition were measured using Fourier Transform Infrared Spectroscopy (FTIR), and results show that the IR absorption peaks shift to higher wave numbers, as the atomic ratio of Na/Na+Ca of the samples increases. In the low wave number region, the wave number of the IR absorption peaks at 424, 576 and 658 cm(-1) and the atomic ratio of Na/Na+Ca of the samples share fine linear correlation, and the correlation coefficients (R2) are, in order, R1(2)=0.9442, R2(2)=0.9283, R3(2)=0.9097. We can utilize infra-red spectrum technologies combined with linear model built by us in this work to predicate the atomic ratio of Na/Na+Ca of the unknown Myanmar jade samples. As the atomic ratio of Na/Na+Ca of the unknown Myamar jade samples equals 0.8, the IR absorption peaks should be at 658.7, 574.5, 422.5 cm(-1). If the wavenumbers of the IR absorption peaks are less than 658.7, 574.5 and 422.5 cm(-1), the atomic ratio of Na/Na+Ca of the unknown Myanmar jade samples is less than 0.8, which is indicating that the unknown Myanmar jade sample isomphacitic jade, while the wavenumbers of the IR absorption peaks are more than 658.7, 574.5 and 422.5 cm(-1), the atomic ratio of Na/Na+Ca of the unknown Myanmar jade samples is more than 0.8, which is indicating that the unknown Myanmar jade sample is jadeitic jade. The studies of this work offer a super-quick time-saving and labor-saving nondestructivetesting method for using infrared spectrum technologies to test Myanmar jade samples, analyze their component and predicate which mineral styles the unknown samples are. PMID- 26672274 TI - [Two-Dimensional Hetero-Spectral Near-Infrared and Mid-Infrared Correlation Spectroscopy for Discrimination Adulterated Milk]. AB - New approach for discriminant analysis of adulterated milk is proposed based on combining hetero-spectral two-dimensional (2D) near-infrared (NIR) and mid infrared (IR) correlation spectroscopy along with multi-way partial least squares discriminant analysis (NPLS-DA). Firstly, 36 pure milk samples were collected and 36 adulterated milk with starch samples (0.01 to 1 g . L(-1)) were prepared by adding appropriate mass of starch into pure milk. Then, one-dimensional NIR transmittance spectra and IR attenuated total reflection spectra of pure milk and adulterated milk with starch were measured at room temperature. And the synchronous 2D NIR-IR (4200~4800 vs. 900~1700 cm(-1)) correlation spectra of all samples were calculated. Due to the trace of adulterants, the synchronous 2D IR NIR correlation spectral differences between adulterated milk with starch and pure milk are very subtle. Consequently, it was impossible to directly distinguish whether the sample was pure milk or adulterated milk. Finally, 2D IR NIR correlation spectra were to build a discriminant model to classify adulterated milk and pure milk. The classification accuracy rates of samples in calibration set and in prediction set were 95.8% and 100% respectively. Also, the NPLS-DA models were built based on 2D NIR and 2D IR correlation spectra, respectively. The classification accuracy rates of samples in prediction set were 95.8%. Comparison results showed that the NPLS-DA model could provide better results using 2D NIR-IR correlation spectra than using 2D NIR, and 2D IR correlation spectra. The proposed method can not only effectively extract the feature information of adulterants in milk, but also explores a new perspective method for detection of adulterated food. PMID- 26672275 TI - [NIRS for Predicting Nutritive Value of Elymus sibiricus]. AB - Siberian wildrye (Elymus sibiricus L.) is one of the predominant pasture species in Qinghai-Tibet plateau of China. It supplies a large number of fodders to domestic animals in spring and winter, and provides a large proportion of the summer and autumn grazing in these alpine regions. Crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF) and in vitro dry matter digestibility (IVDMD) are the most important aspects of nutritive value of forages. A successful application of near infrared spectroscopy (NIRS) in combination with partial least square regression (PLSR) for the determination of four parameters (CP, ADF, NDF and IVDMD) of Siberian wildrye was developed. The standard errors of calibration (SEC, %DM) and Rcal(2) values (in parentheses) were 0.3299(0.9945), 0.7799(0.9499), 1.3430(0.9133), and 1.3762(0.9822) for CP, ADF, NDF and IVDMD equations, respectively. The standard errors of prediction (SEP, %DM) and Rval(2) values (in parentheses) were 0.3621(0.9938), 0.7878(0.9449), 1.3852(0.8907), and 1.4303(0.9790) for CP, ADF, NDF and IVDMD, respectively. A good correlation (r>0.9438) was found between results from NIRS and the traditional chemical method, and residual predictive deviation (RPD) ranged from 3.02 to 12.63. It was concluded that NIR spectroscopic technique associated with chemometrics is sufficiently sensitive to allow the accurate prediction of the concentrations of compo nents (CP, ADF and NDF) and IVDMD of Siberian wildrye. PMID- 26672276 TI - [Preparation of Rubber Accelerator Zinc Diethyldithiocarbamate and Its Spectral Analysis]. AB - In the study, rubber accelerator Zinc diethyldithiocarbamate (EZ) was synthesized firstly. Complex EZ of single crystal was cultivated by solvent evaporation method. EZ was detected and characterized by XRD single crystal diffraction, FTIR and TG-DSC. The micro-structure and intrinsic regularity were revealed. Its highly efficient performance of rubber vulcanization promotion was decided due to its orientation structure? and high order. The result of TG-DSC showed that complex EZ was possessed with a little CS2. The chemical bond types in EZ were revealed by FTIR, the same as single crystal? diffraction testing by different way. The decomposition temperature of EZ was very high. It could provided reference with research on rubber vulcanizing properties by EZ on rubber vulcanizing machine. This study can help the enterprises to designate the working standard tracing detection of EZ industrialized production. Performance index of EZ was judged. The project of EZ industry standard can be declared by the enterprises, written a draft standard on the basis experimental data. PMID- 26672277 TI - [Bare Soil Moisture Inversion Model Based on Visible-Shortwave Infrared Reflectance]. AB - Soil is the loose solum of land surface that can support plants. It consists of minerals, organics, atmosphere, moisture, microbes, et al. Among its complex compositions, soil moisture varies greatly. Therefore, the fast and accurate inversion of soil moisture by using remote sensing is very crucial. In order to reduce the influence of soil type on the retrieval of soil moisture, this paper proposed a normalized spectral slope and absorption index named NSSAI to estimate soil moisture. The modeling of the new index contains several key steps: Firstly, soil samples with different moisture level were artificially prepared, and soil reflectance spectra was consequently measured using spectroradiometer produced by ASD Company. Secondly, the moisture absorption spectral feature located at shortwave wavelengths and the spectral slope of visible wavelengths were calculated after analyzing the regular spectral feature change patterns of different soil at different moisture conditions. Then advantages of the two features at reducing soil types' effects was synthesized to build the NSSAI. Thirdly, a linear relationship between NSSAI and soil moisture was established. The result showed that NSSAI worked better (correlation coefficient is 0.93) than most of other traditional methods in soil moisture extraction. It can weaken the influences caused by soil types at different moisture levels and improve the bare soil moisture inversion accuracy. PMID- 26672278 TI - [NIR Assignment of Magnolol by 2D-COS Technology and Model Application Huoxiangzhengqi Oral Liduid]. AB - Near infrared (NIR) spectroscopy assignment of Magnolol was performed using deuterated chloroform solvent and two-dimensional correlation spectroscopy (2D COS) technology. According to the synchronous spectra of deuterated chloroform solvent and Magnolol, 1365~1455, 1600~1720, 2000~2181 and 2275~2465 nm were the characteristic absorption of Magnolol. Connected with the structure of Magnolol, 1440 nm was the stretching vibration of phenolic group O-H, 1679 nm was the stretching vibration of aryl and methyl which connected with aryl, 2117, 2304, 2339 and 2370 nm were the combination of the stretching vibration, bending vibration and deformation vibration for aryl C-H, 2445 nm were the bending vibration of methyl which linked with aryl group, these bands attribut to the characteristics of Magnolol. Huoxiangzhengqi Oral Liduid was adopted to study the Magnolol, the characteristic band by spectral assignment and the band by interval Partial Least Squares (iPLS) and Synergy interval Partial Least Squares (SiPLS) were used to establish Partial Least Squares (PLS) quantitative model, the coefficient of determination Rcal(2) and Rpre(2) were greater than 0.99, the Root Mean of Square Error of Calibration (RM-SEC), Root Mean of Square Error of Cross Validation (RMSECV) and Root Mean of Square Error of Prediction (RMSEP) were very small. It indicated that the characteristic band by spectral assignment has the same results with the Chemometrics in PLS model. It provided a reference for NIR spectral assignment of chemical compositions in Chinese Materia Medica, and the band filters of NIR were interpreted. PMID- 26672279 TI - [Progress in Application of Two-Dimensional Correlation Spectroscopy for Detection of Food Quality]. AB - In recent years, the food safety and quality has always been a serious issue. Therefore, it is urgent to develop a rapid and widely available method to determine the quality of food. Due to high spectral resolution, good spectral selectivity and good ability of spectrogram analysis, the technology of two dimensional (2D) correlation spectroscopy is an effective method for solving three major problems encountered by the conventional one-dimensional (1D) spectrum: low selectivity of the spectra, difficulty in extracting the information of the spectral feature and difficulty in spectrogram analysis. Therefore, 2D correlation spectroscopy, which is suited to distinguish similar samples hardly distinguished by the conventional 1D spectroscopy, has been successfully applied in many complex biological systems. The developmental process, the experimental way to obtain spectrum, the fundamental mathematical principle and the properties of 2D correlation spectroscopy were introduced in this paper. At the same time, it is pointed out that the origin of weak characteristic bands of substance can be verified in terms of the positive or negative corss peaks in synchronous 2D correlation spectrum combined with the existence or inexistence of corss peaks in asynchronous 2D correlation spectrum. The application of 2D near-infrared, mid-infrared, fluorescence, and raman correlation spectroscopy in the detection of food quality and adulteration, concentrated specifically on diary product, wine, oil, meat, honey, and rice were reviewed. Finally, the limitations and future development prospects were pointed out. PMID- 26672280 TI - [Advance of Development and Application of GC-IR Technology]. AB - The gas chromatograph (GC)-infrared spectroscopy (IR) technique combines the particular separating capacity of GC and the faultlessly with distinguishing capacity of molecular structure of IR, its detective sensitivity is very high and itis used to separate and identify many kinds of complicated compounds from element speciation analysis, natural products, and gasoline. This paper introduces the principle of GC-IR. Three types of interface techniques, light pipe technique, matrix isolation technique and direct deposition technique are compared. Connection type with other detections and factors influencing sensitivity in interface are also introduced. The improvement and achievement in coupling GC system, interface, data processing techniques and its application is reviewed in the present paper. PMID- 26672281 TI - [Purity Detection Model Update of Maize Seeds Based on Active Learning]. AB - Seed purity reflects the degree of seed varieties in typical consistent characteristics, so it is great important to improve the reliability and accuracy of seed purity detection to guarantee the quality of seeds. Hyperspectral imaging can reflect the internal and external characteristics of seeds at the same time, which has been widely used in nondestructive detection of agricultural products. The essence of nondestructive detection of agricultural products using hyperspectral imaging technique is to establish the mathematical model between the spectral information and the quality of agricultural products. Since the spectral information is easily affected by the sample growth environment, the stability and generalization of model would weaken when the test samples harvested from different origin and year. Active learning algorithm was investigated to add representative samples to expand the sample space for the original model, so as to implement the rapid update of the model's ability. Random selection (RS) and Kennard-Stone algorithm (KS) were performed to compare the model update effect with active learning algorithm. The experimental results indicated that in the division of different proportion of sample set (1:1, 3:1, 4:1), the updated purity detection model for maize seeds from 2010 year which was added 40 samples selected by active learning algorithm from 2011 year increased the prediction accuracy for 2011 new samples from 47%, 33.75%, 49% to 98.89%, 98.33%, 98.33%. For the updated purity detection model of 2011 year, its prediction accuracy for 2010 new samples increased by 50.83%, 54.58%, 53.75% to 94.57%, 94.02%, 94.57% after adding 56 new samples from 2010 year. Meanwhile the effect of model updated by active learning algorithm was better than that of RS and KS. Therefore, the update for purity detection model of maize seeds is feasible by active learning algorithm. PMID- 26672282 TI - [Detection of Adulteration in Milk Powder with Starch Near Infrared]. AB - Three China trademarks of milk powder called Mengniu, Yili, Wandashan were taken as testing samples. Each of them mixed varied amount of starch in different gradient, which were consisted of 32 adulterated milk powder samples mixed with starch, was taken as standard samples for constructing predicted model. To those 32 samples, the reflecting spectrum characteristics in middle wave of near infrared spectrum with Near Infrared Spectrum Analyzer (Micro NIR 1700) produced by JDSU Ltd. USA were collected for five repeats in five different days. The time span was nearly two months. Firstly, we build the model used the reflecting spectrum characteristics of those samples with biomimetic pattern recognition (BPR) arithmetic to do the qualitative analysis. The analysis included the reliability of testing result and stability of the model. When we took ninety percent as the evaluation threshold of testing result of CAR (Correct Acceptance Rate) and CRR (Correct Rejection Rate), the lowest starch content of adulterate milk powder in all tested samples which the tested result were bigger than that abovementioned threshold was designated CAR threshold (CAR-T) and CRR threshold (CRR-T). CAR means the correct rate of accepting a sample which is belong to itself, CRR means correct rate of refusing to accept a sample which is not belong to itself. The results were shown that, when we constructed a model based on the near infrared spectrum data from each of three China trademark milk powders, respectively, if we constructed a model with infrared spectrum data tested in a same day, both the CAR-T and CRR-T of adulterate starch content of a sample can reach 0.1% in predicting the remainder infrared spectrum data tested within a same day. The three China trademarks of milk powder had the same result. In addition, when we ignored the trademarks, put the spectrum data of adulterate milk powder samples mixed with the same content of starch of three China trademarks milk powder together to construct a model, the CAR-T of mixed starch content of a sample may reach 0.1%, the CRR-T can reach 1%, if the model construction and predicting were performed with near infrared spectrum data tested in a same day. However, the CAR-T can just stably reach up to 5% and the CRR-T have the same result, if the model construction and predicting were crossly performed with mixed near infrared spectrum data tested in different days. Furthermore, the correct recognizing threshold mixed starch of a sample can stably reach up to 1% and the CAR-T can reach 5%, if the model construction was based on near infrared spectrum data combined the previous four days to predict the output of the another day. On the other hand, we also engaged quantitative analysis to the starch content in milk power with two kinds of arithmetic (PLSR, LS-SVR). In contrast with the testing outputs, the reliability of both the CAR-T and CRR-T in qualitative analysis was further validated. PMID- 26672283 TI - [Comparison of Three Spectroscopies for the Determination of Composition of LDPE/PP Blend with Partial Least-Squares]. AB - This paper presented an application of mid-infrared (MIR), near-infrared (NIR) and Raman spectroscopies for collecting the spectra of 31 kinds of low density polyethylene/polyprolene (LDPE/PP) samples with different proportions. The different pre-processing methods (multiplicative scatter correction, mean centering and Savitzky-Golay first derivative) and spectral region were explored to develop partial least-squares (PLS) model for LDPE, their influence on the accuracy of PLS model also being discussed. Three spectroscopies were compared about the accuracy of quantitative measurement. Consequently, the pre-processing methods and spectral region have a great impact on the accuracy of PLS model, especially the spectra with subtle difference, random noise and baseline variation. After being pre-processed and spectral region selected, the calibration model of MIR, NIR and Raman exhibited R2/RMSEC values of 0.9906/2.941, 0.9973/1.561 and 0.9972/1.598 respectively, which corrsponding to 0.8876/10.15, 0.8493/11.75 and 0.8757/10.67 before any treatment. The results also suggested MIR, NIR and Raman are three strong tools to predict the content of LDPE in LDPE/PP blend. However, NIR and Raman showed higher accuracy after being pre-processed and more suitability to fast quantitative characterization due to their high measuring speed. PMID- 26672284 TI - [Prediction the Soluble Solid Content in Sugarcanes by Using Near Infrared Hyperspectral Imaging System]. AB - In order to explore the feasibility of prediction soluble solid contents (SSC) in sugarcane stalks by using near infrared hyperspectral imaging techniques, two hundred and forty sugarcane stalks which come from three different varieties were studied. After obtaining the raw hyperspectral images of sugarcane stalks, the spectral information and textural features were discussed respectively. The prediction models were established by using partial least squares regression (PLSR), principal components regression (PCR) and least squares support vector machines (LS-SVM) algorithms. Besides, three different selected wavelengths algorithms such as successive projection (SPA) algorithms, intervals partial least squares (iPLS) algorithms and uninformation variables elimination (UVE) algorithm were analyzed after building partial least squares regression model. The results indicate that partial least squares regression model based on spectral features can be an steady model to predict SSC and the correlation coefficient (R2) of calibration sets and prediction sets are 0.879, 0.843. The root mean square errors of calibration sets and prediction sets are 0.644, 0.742 respectively. The obtained 105 wavelengths which were selected by UVE algorithm are effective spectral features. The R2 results of calibration sets and prediction sets of its PLSR model are 0.860, 0.813. The root mean square errors of calibration sets and prediction sets are 0.693, 0.810 respectively PMID- 26672285 TI - [Experimental Investigation of Infrared Spectral Emissivity of Copper at 300~1123 K]. AB - In this study, a new reflective experimental apparatus, which can measure the spectral emissivity of opaque materials accurately and real timely, has been developed based on the Kirchhoff's law by using the GaAs semiconductor laser as the standard radiation source. The spectral emissivity of brass and red copper at wavelength lambda=1.55 MUm were investigated systematically with the temperatures range from 300 up to 1123 K by using this apparatus and the influence of temperature, oxidation and heating time on the spectral emissivity of two kinds of specimens were also discussed. The experimental data showed that the spectral emissivity increased with increase of temperature and appeared its peak value and valley value when the thickness of oxide film was at some degree. The spectral emissivity of red copper was always greater than that of brass. The formula for calculating the thickness of oxide film was derived from the reflection model composed of a metal and oxide film, then the peak and valley thickness of the red copper were estimated according to this model. The experimental data of constant temperature measurements showed that the spectral emissivity had a slight increase with heating time increasing. Two hours later, the spectral emissivity of two kinds of samples trended to be stable when the thickness of oxide film was at some degree. The values of spectral emissivity at high temperatures were always larger than that of low temperatures. The results of this study will further enrich spectral emissivity data of copper and provide experimental basis for its application. PMID- 26672286 TI - [Infrared Spectral Characteristics of Ambers from Three Main Sources (Baltic, Dominica and Myanmar)]. AB - Infrared spectra of ambers from Baltic, Dominica and Myanmar are obtained by Specular Reflection and KBr Pellet Transmission Methods. Although the infrared spectra of these ambers present similar features for ambers from different locations, refined differences in location and intensity of absorption peaks could be identified among them. Between 3000 and 2800 cm(-1), two obvious bands with a weak shoulder peak are seen in the Baltic amber spectrum, whereas there are two bands in the Dominica's and three bands in the Myanmar's. In region of 1740~1690 cm(-1), one band appears at 1732 cm(-1) in the spectra of the Baltic amber sample, distinctly different from those of the Dominican and Myanmar ambers which have a doublet at 1730 and 1695 cm(-1). For the Dominican amber, the intensity of 1730 cm(-1) is much stronger than that of 1695 cm(-1), being contrary to the spectra of the Myanmar amber, whose intensity of 1730 cm(-1) is weaker than that of 1695 cm(-1). Within region of 1300~1000 cm(-1), Baltic amber can be distinguished from other two origin ambers by a horizontal shoulder, often called "Baltic shoulder", with a definite band at 1163 cm(-1). Spectra of the Dominican amber show a unique band at 1240 cm(-1), while spectra of the Myanmar amber have a triplet at 1224, 1130 or 1154 cm(-1) and 1033 cm(-1), like "wave of mountain" altogether. Ratios of absorption intensity of 1381 vs. 1456 cm(-1) are about 0.9, 0.8 and 0.7 respectively for the Baltic, Dominican and Myanmar ambers. These differences of absorption spectra could be used as the identifiable characteristics corresponding to the ambers locality. The correlation between the ambers' infrared spectra and localities is probably due to their age, plant provenance and geological environment indivadually. On the basis of presence and intensity of the bands attributed to exocyclic methylene groups, it is suggested that the Myanmar amber formed earliest, followed by Baltic and then the youngest Dominican. These finding reveals that infrared spectroscopy may have significance for identifing amber locality, and thus potentially have archeological implications in determining source of some ancient ambers. PMID- 26672287 TI - [A Modified Procedure to Isolate Synchronous Cells from Yeasts with Continuous Percoll Density Gradient and Their Raman Discrimination]. AB - A modified procedure of Percoll density gradient centrifugation was developed to isolate and fractionate synchronous cells from stationary phase (sp) cultures of different yeast strains, as well as Raman spectra discrimination of single yeast cells was reported. About 1.75 mL Percoll solution in 2 mL polypropylene centrifugal tube was centrifuged at 19,320 g, 20 degrees C with an angle rotor for 15 min to form continuous densities gradient (1.00~1.31 g . mL(-1)), approximately 100 MUL sample was overlaid onto the preformed continuous density gradient carefully, subsequently, centrifuged at 400 g for 60 min in a tabletop centrifuge equipped with a angle rotor at 25 degrees C. Yeast samples could be observed that the suspensions were separated into two cell fractions obviously. Both fractions of different yeast strains were respectively determined by differential interference contrast (DIC), phase contrast microscope and synchronous culture to distinguish their morphological and growth trait. The results showed that the lower fraction cells were unbudded, mostly unicellular, highly refractive, homogeneous and uniform in size, and represented growth characteristic synchronously; Their protoplasm had relatively high density, and contained significant concentrations of glycogen; all of which were accordant with description of quiescent yeast cells and G0 cells in previously published paper. It was shown that lower fraction was quiescent cells, synchronous G0 cells as well. A Raman tweezers setup was used to investigate the differences between two fractions, G0 cells and non G0 cells, at a single cell level. The result showed that both G0 cells and the non G0 cells had the same characteristic peaks corresponding biological macromolecules including proteins, carbohydrates and nucleic acids, but all characteristic peak intensities of G0 cells were higher than that of non G0 cells, implied that the macromolecular substance content of G0 cells was more higher. Principal component analysis (PCA) was performed between G0 cells and non G0 cells, the results showed that the chemical composition content among the synchronization G0 cells has less difference, and G0 cells were homogeneous but non G0 cells were heterogeneous, indicating single cell optical tweezers Raman spectroscopy could identify the synchronous and asynchronous cells. The modified method is feasible, economical and efficient highly. G0 synchronous cells of most yeast strains could be isolated by a modification of Percoll density gradient centrifugation. PMID- 26672288 TI - [Study on the Effects of Ginsenoside Rb1 on DPPC Bilayers by Using Thermo-Raman Spectrum and DSC]. AB - The research on the interactions between Ginsenosides and biomembranes plays a crucial role in thorough understanding the pharmacological activity and biologyical effect of Chinese medicine Panax ginseng. With the bilayer structure, DPPC often serves as an simulation model of the cell membrane to study the role of drug molecules and cell membranes. Ginsenoside Rb1, one of the most important components of Panaxginseng, playing the significant roles of pharmacological effects and biological properties. Raman and differential scanning calorimetry (DSC) are respectively a powerful tool for discussing the molecular interaction, and a kind of general technology by which researching the bilayer monomer structures and its interactions with drug molecules. However, rarely research reports on the interactions between drug molecules and biomembranes by means of both technologies above. In this paper, the influence of ginsenoside monomer Rb1 on DPPC membrane bilayers was investigated by thermo-Raman and DSC. In Raman spectra, the changes of DPPC molecule have been observed before and after interacted with ginsenoside Rb1, the data analysis indicates three aspects: the O C-C-N+ polar head group skeleton, C-C stretching vibration area, and the C-H bond stretching vibrarion in terminated methyl group of alkyl chains. The results showed that ginsenoside Rb1 molecule with certain concentration has not changed the gauche conformation of the polar head backbone group in DPPC bilayers, the order of the internal molecular chain and the lateral chain-chain packing have been decreased as the temperature increased, the lateral disposed disorder has been increased. The changes of some thermodynamic constants obtained by DSC experiment such as phase transition temperature (Tm), the temperature at which the transition is half completed (DeltaT1/2), and the transition enthalpy normalized per mol of DPPC (AH) have been showed further results of the thermo Raman experiments, with increasing the concentration of ginsenoside Rb1, the pre transition temperature of DPPC bilayers dropped immediately with small amount of the Rb1 drug when the containtion was only 5 mol% and the whole system has been destructed at the same time, the main phase transition peak showed as a new little shoulder seam, however, both pre- and main transition peak disappeared completely until the drug concentration increased to 20 mol%, the phase transition temperature of DPPC has been reduced significantly, and the fluidity of bilayers has been increased. Both experiments indicated that the strong effects of ginsenoside Rb1 on DPPC. PMID- 26672289 TI - [Research on Identification and Determination of Pesticides in Apples Using Raman Spectroscopy]. AB - Raman spectroscopy combined with chemometric methods has been thought to an efficient method for identification and determination of pesticide residues in fruits and vegetables. In the present research, a rapid and nondestructive method was proposed and testified based on self-developed Raman system for the identification and determination of deltamethrin and acetamiprid remaining in apple. The peaks of Raman spectra at 574 and 843 cm(-1) can be used to identify deltamethrin and acetamiprid, respectively, the characteristic peaks of deltamethrin and acetamiprid were still visible when the concentrations of the two pesticides were 0.78 and 0.15 mg . kg(-1) in apples samples, respectively. Calibration models of pesticide content were developed by partial least square (PLS) algorithm with different spectra pretreatment methods (Savitzky-Golay smoothing, first derivative transformation, second derivative transformation, baseline calibration, standard normal variable transformation). The baseline calibration methods by 8th order polynomial fitting gave the best results. For deltamethrin, the obtained prediction coefficient (Rp) value from PLS model for the results of prediction and gas chromatography measurement was 0.94; and the root mean square error of prediction (RMSEP) was 0.55 mg . kg(-1). The values of Rp and RMSEP were respective 0.85 and 0.12 mg . kg(-1) for acetamiprid. According to the detect performance, applying Raman technology in the nondestructive determination of pesticide residuals in apples is feasible. In consideration of that it needs no pretreatment before spectra collection and causes no damage to sample, this technology can be used in detection department, fruit and vegetable processing enterprises, supermarket, and vegetable market. The result of this research is promising for development of industrially feasible technology for rapid, nondestructive and real time detection of different types of pesticide with its concentration in apples. This supplies a rapid nondestructive and environmentally friendly way for the determination of fruit and vegetable quality and safety. PMID- 26672290 TI - [Study on Vibrational Spectra Characteristics of Gem-Quality Natrolite]. AB - Recently, there is a batch of colorless faceted gem-quality natrolite appear in the international jewelry market. In order to provide some information that can help us to distinguish them from the imitations. The infrared spectrometer and Raman spectrometer were employed to study the characteristics of the vibrational spectrum of three natrolite samples in this article. The typical infrared spectra shows that: the absorption region 4000~1200 cm(-1) is induced by stretching vibration of the hydroxyl group, the strong absorption peaks range from 1200~600 cm(-1) are relative with the anti-symmetry and symmetry stretching vibration of tetrahedral T-O bonds (T=Si or Al). The Raman spectra scattering peaks are located in the range of 300~600 and 700~1200 cm(-1). The low intensity Raman scattering spectrum in the range of 300~360 cm(-1) corresponds to the vibration of the water molecules in the crystal. The medium intensity Raman scattering spectrum is assigned to the deformation of SiO4 tetrahedra. The Raman spectra scattering peak at 726 cm(-1) is assigned to the stretching vibration of Al-O; The Si-O stretching vibration displays the Raman spectra scattering peaks at 974, 1038 and 1084 cm(-1). PMID- 26672291 TI - [Study on Synthesis and Luminescence Mechanism of Novel Green Sr3Y(PO4)3:Ce3+, Tb3+ Phosphors]. AB - A novel green light-emitting phosphor Sr3Y(PO4)3Ce(3+), Tb(3+) was synthesized by the traditional high temperature solid state reaction method. Luminescence mechanism and crystal structure were investigated by X-Ray Diffraction (XRD) and photoluminescence spectra (PL). The XRD patterns demonstrate that the samples belong to the single phase of Sr3Y(PO4)3 in experimental doping concentrations range. Obviously, the excitation band of Sr3Y(PO4)3:Tb(3+) and the emission of Sr3Y(PO4)3:Ce(3+) have a significant spectral overlap in the wavelength range of 330~380 nm, which implies the great possibility of an efficient ET from Ce(3+) to Tb(3+). Under the 315 nm ultraviolet excitation, a blue emission(320~420 nm) from Ce(3+) and a yellowish-green emission (480~500, 530~560 nm) from Tb(3+) were obtained from Sr3Y(PO4)3:Ce(3+), Tb(3+). When the Ce(3+) concentration was 7%, the emission could be adjusted from blue to green region by tuning the Tb(3+) doping concentrations from 1% to 50% through an energy transfer process. This text plot the schematic energy levels of Ce(3+), and Tb(3+) with electronic transitions and energy transfer processes in Sr3Y(PO4)3:Ce(3+), Tb(3+), which disclose the electron motion processes of Sr3Y(PO4)3:Ce(3+), Tb(3+). From the dependence of relative emission intensity of Ce(3+), Tb(3+) ((5)D4 --> (7)Fj) and ET efficiency from Ce(3+) to Tb(3+) on the concentrations of Tb(3+), It can be seen that the relative intensity of Tb(3+) and the values of etaET increase gradually with the increasing of Tb(3+) as well as the relative intensity of Ce(3+) decreases remarkably. The largest energy transfer efficiency reaches as high as 80% when the concentration of Tb(3+) was 50%, demonstrating the efficient energy transfer from Ce(3+) to Tb(3+). The CIE chromaticity coordinate positions are plotted, as can be seen the emitting color of Ce(3+) and Tb(3+) singly doped Sr3Y(PO4)3:Ce(3+), Tb(3+) phosphor are blue and yellowish green, respectively. The emitting color of samples Sr3Y(PO4)3:Ce(3+), Tb(3+) changes from blue region to green region with the rising doping contents of Tb(3+). Sr3Y(PO4)3:Ce(3+) and Tb(3+) phosphor can be used as a green light-emitting phosphor in white LED devices and LCD backlights. PMID- 26672292 TI - [Photosynthetic Parameters Inversion Algorithm Study Based on Chlorophyll Fluorescence Induction Kinetics Curve]. AB - The fast chlorophyll fluorescence induction curve contains rich information of photosynthesis. It can reflect various information of vegetation, such as, the survival status, the pathological condition and the physiology trends under the stress state. Through the acquisition of algae fluorescence and induced optical signal, the fast phase of chlorophyll fluorescence kinetics curve was fitted. Based on least square fitting method, we introduced adaptive minimum error approaching method for fast multivariate nonlinear regression fitting toward chlorophyll fluorescence kinetics curve. We realized Fo (fixedfluorescent), Fm (maximum fluorescence yield), sigmaPSII (PSII functional absorption cross section) details parameters inversion and the photosynthetic parameters inversion of Chlorella pyrenoidosa. And we also studied physiological variation of Chlorella pyrenoidosa under the stress of Cu(2+). PMID- 26672293 TI - [Planktonic Algae's Distribution and Correlation with Dissolved Organic Matters' Fluorescence in the End of the Three Gorges Reservoir's Back Water Zone]. AB - For researching the community structure, composition, and distribution of the planktonic algae in the Three Gorges Reservoir (TRG), especially, within TRG water levels' fluctuating, mpacting to water quality with the algae's growing, 6 sampling cites in the end of the TGR's back water zone, from Chaotianmen to Taihonggang Town, are chosen to monitor, at the sensitive stages time of algal bloom between March to May 2012, namely, water levels lowing from the highest impounding. The community's structure, composition, and distribution of the planktonic algae in the TGR, and the correlation of water quality parameters and DOM's fluorescence features with algae density, are obtained. According to the experimental results, blue algae fibre, chlorella, melosira, navicula are the dominated algae in the end of the TGR's back water zone, from Chaotianmen to Taihonggang Town, algae density are 0.40~0.56 * 10(6), 1.9~0.8 * 10(6), 0.36~0.25 * 10(6), 0.42~0.15 * 10(6) cells . L(-1) respectively. Besides, anabaena, phormidium, cladophora, feather, ovate algae are existing in only limited 2 sections. The fitting results reveal obvious linear correlation of the EEM characteristics of DOM with the 4 kinds of dominated algal density, which could be useful conference for the algae bloom monitor, conveniently and effectively. PMID- 26672294 TI - [Sensitive Determination of Chondroitin Sulfate by Fluorescence Recovery of an Anionic Aluminum Phthalocyanine-Cationic Surfactant Ion-Association Complex Used as a Fluorescent Probe Emitting at Red Region]. AB - Determination of chondroitin sulfate in the biomedical field has an important value. The conventional methods for the assay of chondroitin sulfate are still unsatisfactory in sensitivity, selectivity or simplicity. This work aimed at developing a novel method for sensitive and selective determination of chondroitin sulfate by fluorimetry. We found that some kinds of cationic surfactants have the ability to quench the fluorescence of tetrasulfonated aluminum phthalocyanine (AlS4Pc), a strongly fluorescent compound which emits at red region, with high efficiency. But, the fluorescence of the above-mentioned fluorescence quenching system recovered significantly when chondroitin sulfate (CS) exits. Tetradecyl dimethyl benzyl ammonium chloride(TDBAC) which was screened from all of the candidates of cationic surfactants was chosen as the quencher because it shows the most efficient quenching effect. It was found that the fluorescence of AlS4Pc was extremely quenched by TDBAC because of the formation of association complex between AlS4Pc and TDBAC. Fluorescence of the association complex recovered dramatically after the addition of chondroitin sulfate (CS) due to the ability of chondroitin sulfate to shift the association equilibrium of the association, leading to the release of AlS4Pc, thus resulting in an increase in the fluorescence of the reaction system. Based on this phenomenon, a novel method with simplicity, accuracy and sensitivity was developed for quantitative determination of CS. Factors including the reaction time, influencing factors and the effect of coexisting substances were investigated and discussed. Under optimum conditions the linear range of the calibration curve was 0.20~10.0 MUg . mL(-1). The detection limit for CS was 0.070 MUg . mL(-1). The method has been applied to the analysis of practical samples with satisfied results. This work expands the applications of AlS4Pc in biomedical area. PMID- 26672295 TI - [Lanthanum Coordination Polymer Based on Benzimidazole-Dicarboxylic Acid and Phenanthroline: Crystal Structure, Fluorescence and Fluorescent Sensing for Organic Small Molecules]. AB - Two new complexes, {[Eu3(bidC)4(phen)2(NO3)] . 2H2O}n, (1) and [Tb2(bidC)3(H2O)2] (2) (bidc=benzimidazole-dicarboxylate, phen=1, 10-phenanthrolIne) were synthesized. Complex 1 shows 1D chain structure. The asymmetric unit of 1 contains three crystallographically different Eu(3+), Eu(1)O6N2, Eu(2)O8 and Eu(3)O6N2. Complex 2 reveals 2D structure. It contains two crystallographically similar Tb(3+), Tb(1)O8 and Tb(2)O8. Complex 1 displays the emission peaks at 581, 593, 615, 654 and 702 nm, corresponding to the (5)D0-->(7)FJ (J=0-4) transitions of Eu(3+). The most intense emission at 615 nm is attributed to the (5)D-->(7)F2 transition, implies a red emission light of 1. The intensity rations I((5)D0/(7)F2)/I((5)D0/(7)F1) is about 2.5, indicating the chemical environment around Eu(3+) does not have an inversion center. Complex 2 exhibits four emission peaks at 492, 545, 584 and 622 nm, corresponding to the (5)D4-->(7)FJ (J=6-3) transitions of Tb(3+). The emission band at 545 nm corresponds to the (5)D4- >(7)F5 transition of the Tb(3+), which gives an intense green luminescence output for the solid sample. Notably, the solvent-dependent luminescence behavior of complexes 1 and 2 was discussed. They show highly selective for nitrobenzene via a fluorescence quenching mechanism. The highly selective and sensitive sensing nitrobenzene leads to its application in environmental system. PMID- 26672296 TI - [Excitation-Emission Matrix Fluorescence Spectra Characteristics of DOM in a Combined Constructed Wetland]. AB - Using three-dimensional fluorescence technology, we studied fluorescent characteristics of two polluted rivers by a surface flow+vertical flow combined constructed wetlands of dissolving organic matter. The results showed that (1) the main sources of water-soluble humic organic matter in constructed wetland was biological metabolic input instead of terrigenous input; (2) in the later section of the surface flow constructed wetland, part of proteinoid substance changed into fulvic acid-like substance, which showed that the composition of dissolved organic matter and material structure tended to be stable after surface flow combined constructed wetland treatment; (3) it was of great significance that surface flow constructed wetland in structure transformation of water soluble organic matter, which could significantly improve the stability of water soluble organic matter. Surface flow+vertical flow combined constructed wetland process of dissolved organic matter had a good removal effect. PMID- 26672297 TI - [Determination of H2S in Rat Intestinal Perfusion Solution Based on Fluorescence Analysis]. AB - Under alkaline conditions, Fluorescein mercury has strong fluorescence, however, when it met S(2-), its fluorescence would quench, in view of the above, a fluorescence method for determination of H2S in biological samples was established. In the 0.1 mol . L(-1) NaOH dilution, when the concentration of fluorescein Mercury and Na2S was 5.0 * 10(-5) and 1.0 * 10(-5) mol . L(-1) respectively, the fluorescence intensity of system was determined at 522 nm. The results showed that, at the range of 4.0 * 10(-7)~2.0 * 10(-6) mol . L(-1), the concentration decreasing of H2S and fluorescence intensity had good linear relationship, r=0.9980, the RSD of precision test was 4.59% (n=7), the detection limit was 3.5 * 10(-8) mol . L(-1), the content of H2S in the sample were 1.01 * 10(-6) and 1.15 * 10(-6) mol . L(-1), and the recovery rate was 95.8%~101.0%, the method has the advantages of simple operation, high sensitivity, good selectivity, can accurately determine of H2S in intestinal perfused solution, and provides the basis for the determination of endogenous H2S. PMID- 26672298 TI - [Authentication of Age of Bloodstains Using UV Visible Reflection Spectrum]. AB - The age of bloodstains is tightly related to the time elapsed since the crime was committed. The inference of the time that the crime was committed is of great significance to solve the case, and it was also a difficult problem in judicial authentication. Therefore, establishing a method of rapid determination of bleeding time is very necessary. Using a UV-visible spectrometer with a reflection accessory called ISR-240A and whiteboard as a reference standard, the reflection spectra of blood gauze, aluminum, glass and plastic were measured every hour under the condition of 16 degrees C and 70% humidity within 8 hours. Using SPSS to process the data, R541/R577 was figured out and linear fitting was completed. The same method was carried on on the gauze of blood at 24 degrees C. The results showed that, within 8 hours, spectral reflectance values of blood at 541 and 577 nm increased gradually with the passage of injury time. In addition to the R2 of the glass with blood is 0.769, the rest of the R2 were greater than 0.900. The values of F were greater than F0.05 (1, 6) = 5.59. Therefore, the linear regression model is significant meaningful. The method of using a UV Visible spectrometer without doing any operations of the test samples is simple. Moreover, it does no harm to the further inspection in aspects of personal information, which is suitable for the judicial practice. PMID- 26672299 TI - [Study on the Character Relationship Between the Density and Susceptibility of the Rock and the Reflection Spectrum]. AB - It chooses 15 kinds of rock from the three major rock categories as the rock samples (the number of rock samples is 208) and obtains the density, susceptibility and reflection spectrum at the wave band of 350~2500 nm. It calculates the correlative coefficients with the aim of studying the characteristic relationship between the property (including the density and the susceptibility) of the rock and the reflectivity. It concludes the wave band of the reflection spectrum which owes the prospect to discuss the density and susceptibility of the rock qualitatively or quantitatively, meanwhile, it sums up the characteristic of the curves of the correlative coefficients. In this paper, the discussion and analysis based on the results show that the study on the character relationship between the property of rock (density and susceptibility) and the reflection spectrum is meaningful and workable. PMID- 26672300 TI - [Spectral Study on the Effects of Angle-Tuned Filter Wedge Angle Parameter to Reflecting Characteristics]. AB - Three-port tunable optical filter is a key device in the all-optic intelligent switching network and dense wavelength division multiplexing system. The characteristics of the reflecting spectrum, especially the reflectivity and the isolation degree are very important to the three-port filter. Angle-tuned thin film filter is widely used as a three-port tunable filter for its high rectangular degree and good temperature stability. The characteristics of the reflecting spectrum are greatly influenced not only by the incident angle, but also by the wedge angle parameter of the non-paralleled wedge thin film filter. In the present paper, the influences of the wedge angle parameter to the reflectivity and the half bandwidth are analyzed, and the reflecting spectrum characterstics are simulationed in different wedge angle parameter and polarity. The wedge angle-tuned thin film filter with 0.8 degrees wedge angle parameter is fabricated. The experimental results show that keeping the wedge angle the same orientation to the incident angle will worsen the reflectivity and the rectangular degree of the reflecting spectrum. However, keeping the wedge angle orientation reverse to the incident angle will enhance the reflectivity and decrease the bandwidth, which will give higher reflectivity and isolation degree to the three-port filter than that of high parallel degree angle-tuned thin film filter. PMID- 26672301 TI - [Modeling Soil Spectral Reflectance with Different Mass Moisture Content]. AB - The spatio-temporal distribution and variation of soil moisture content have a significant impact on soil temperature, heat balance between land and atmosphere and atmospheric circulation. Hence, it is of great significance to monitor the soil moisture content dynamically at a large scale and to acquire its continuous change during a certain period of time. The object of this paper is to explore the relationship between the mass moisture content of soil and soil spectrum. This was accomplished by building a spectral simulation model of soil with different mass moisture content using hyperspectral remote sensing data. The spectra of soil samples of 8 sampling sites in Beijing were obtained using ASD Field Spectrometer. Their mass moisture contents were measured using oven drying method. Spectra of two soil samples under different mass moisture content were used to construct soil spectral simulation model, and the model was validated using spectra of the other six soil samples. The results show that the accuracy of the model is higher when the mass water content of soil is below field capacity. At last, we used the spectra of three sampling points on campus of Peking University to test the model, and the minimum value of root mean square error between simulated and measured spectral reflectance was 0.0058. Therefore the model is expected to perform well in simulating the spectrum reflectance of different types of soil when mass water content below field capacity. PMID- 26672302 TI - [On the Tributylphosphate-Based Super-Concentrated HCl System]. AB - We reported a new super-concentrated hydrochloric acid system prepared by using tri-n-butyl phosphate (TBP)-constructed reversed micelles at ambient temperature and pressure. According to the titration result, the molar ratio of H+ to H2O (denoted as nH+/nH2O) in the super-concentrated HCl range from 0.50 to 1.50 which are higher than that in saturated aqueous HCl bulk solution (0.28). Significant a moment of hydrochloric acid is confined in W/O reversed micelles. Therefore, the behavior and status of HCl are different from those of conventional bluk solution. FTIR spectroscopic results demonstrate that a significant amount of HCl remains in the molecular form rather than being ionized into H+ and Cl-. Thus, super-concentrated HCl provides an extraordinary chemical environment which may have significant influence on certain substances. We found that the color of the solution is reddish brown when copper ion is dissolved in super-concentrated HCl, while the color of the saturated HCl aqueous solution (37 Wt%) containing copper ion is green. That is to say, the copper ions exist in a special state under the unique chemical environment of super-concentrated HCl. UV-Vis-NIR spectra indicate that both d-d transition band and charge transfer transition band of copper ions in super-concentrated HCl solution underwent significant variations. In addition, copper ions also have obvious influence on the hydrogen bond network among HCl in the super-concentrated HCl solution. Remarkable variation is introduced in the H-Cl stretching band in FTIR spectra. PMID- 26672303 TI - [Changes of Forest Canopy Spectral Reflectance with Seasons in Lang Ya Mountains]. AB - The physiological mechanism and ecological structure of forest trees can change with the changes of years. In a certain extent, the changes were expressed through the canopy spectral features. The mastery of changing rules about spectral characteristics of trees over the years is benefit to remote sensing interpretation and provide scientific basis for the classification of different trees. The study adopted high-resolution spectrometer to measure the canopy spectral characteristics for seven major deciduous trees and seven evergreen trees to gain the spectrum curve of four different ages and calculate the first derivative curve. The analysis of changing rules about spectral characteristics of different deciduous trees and evergreen trees and the comparison of changes about spectrum of various trees in the visible and infrared band could find the best year and best band for identification of trees. The results showed that the canopy spectral reflectance of deciduous and evergreen trees increases with the increase of age. And the spectral changes of two species were most obvious in the near infrared band. PMID- 26672304 TI - [MAX-DOAS Tomography Reconstruction for Gas Plume]. AB - In order to achieve precisely two-dimensional spatial distribution reconstruction of smoke plume, passive MAX-DOAS tomography is established, the measurement of the spatial distribution of the exhaust plume is implemented by more passive multi-axis differential absorption spectrum system. First, the multi-axis differential absorption spectrum system and its mechanism of inverse gas concentration are introduced in the paper. Then, algebra iterative algorithm is adopted to extract the information of the trace gas concentration in reconstruction simulation with different models and different scanning optical path, and the reconstruction program is designed. Then, the numerical simulation results are compared. Finally, a platform of multi-axis differential absorption optical tomography system is set up, a field campaign was carried out. The numerical simulation results show that the MAX-DOAS tomography can accurately reconstruct two-dimensional spatial distribution of plume model, the re- construction error of MAX-DOAS tomography with four light sources is about a third of the reconstruction error with double light sources, moreover, the reconstruction time is about a quarter of the reconstruction time of double light sources, and the reconstruction error of the twin peaks model is greater than that of the one peak model. Field test results show that the integral data of reconstruction image is consistent with the measured projection data of multi axis differential absorption spectrum, the spatial distribution reconstruction of plume is in line with the actual situation. Studies have shown that the result of numerical simulation and field test results have consistency. PMID- 26672305 TI - [Components of Urinary Nanocrystals and Their Influence on Formation of Calcium Oxalate Stones]. AB - High-resolution transmission electron microscopy, X-ray diffraction, selected area electron diffraction (SAED), and energy dispersive spectroscopy (EDS) were accurately performed to analyze the components of nanocrystals in the urine of patients with calcium oxalate (CaOx) stones. XRD, SAED and FFT detected the presence of calcium oxalate monohydrate (COM), uric acid (UA), and calcium phosphate (CaP). EDS detected the elements of C, O, Ca, with a small amount of N and P. These results showed that the main components of urinary nanocrystals were COM, with a small amount UA and phosphate. HRTEM observation showed that the particle size of urinary nanocrystals was dozens of nanometers. The result was consistent with the calculation by Debye-Scherrer equation. When the urine was filtered through a microporous membrane of 0.45, 1.2, and 3 MUm, respectively, the number of diffraction peaks of the obtained urine crystallites increased with the increased pore size, indicating the increase of urinary crystallite species. Crystal nucleation, growth, aggregation, and adhesion of crystals to the renal epithelial cells are important processes for CaOx stone formation. The presence of a large amount of COM crystals in patients' urine is a critical factor for CaOx stones formation. Nano UA and CaP crystallite can induce the CaOx stone formation as central nidus. PMID- 26672306 TI - [A Method for Retrieving Thermospheric O/N2 from Measurements of OI 130.4 nm Dayglow]. AB - Thermospheric O/N2 can be retrieved from the radiance of OI 130.4 nm dayglow. In the paper, the algebraic relationship between the two variables is established, and the characteristics of the radiance varying with observing angle and solar zenith angles are discussed, based on which the look-up tables of the regularization factors are made up, thus putting up a method for retrieving thermospheric O/N2 from measurements of OI 130.4 nm dayglow and meanwhile introducing a correcting coefficient in the algorithm to dismiss the error brought about by the difference between the ideal atmosphere representative by NRLMSISE-00 and the real atmosphere. Finally, the simulated dayglow radiance data of Oct 1, 2002 are used as an example to testify the validation of the algorithm. The results demonstrated that the algorithm is able to reconstruct most of the features of O/N2 and has an obvious advantage over the conventional algorithm. PMID- 26672307 TI - [Influence of the Composition of the Initial Mixtures on the Physicochemical and Biological Properties and Spectral Characteristics of Composts]. AB - In this work, biogas residues, the remnant of the anaerobic digestion, was used for composting with livestock manure as the co-substrate. It is important for improving the soil quality in China, because the negative influence of biogas residues being utilized directly as organic fertilizer (a mainstream way of disposing biogas residues in China) on the soil could be eliminated or mitigated via composting. The composition of composting substrate has a great influence on the composting process. To explore the influence of the composition of the initial mixtures on the physicochemical properties and spectroscopic characteristics of composts, fifteen co-composting of biogas residue, pig manure and chicken manure, with different material ratios, were carried out. Physicochemical and biological indicators were determined. Meanwhile, spectroscopic methods, such as UV-Vis, synchronous fluorescence and 3D-EEM spectra were used for identifying characteristic spectral parameters companied with FRI and PARAFAC. Therefore, spectroscopic characteristics of composts were characterized. The relationship between physicochemical properties of composts and the composition of the initial mixtures was established using CCA. Similarly, that between spectroscopic characteristics of composts and the composition of the initial mixtures was also established. The results showed that: physicochemical properties of composts exhibits a significant correlation with the composition of the initial mixtures. A significant correlation between spectroscopic characteristics of composts and the composition of the initial mixtures was also observed. In the two CCA, the former four axes account for 83.9% and 97.5% of the total sample variation. The influence of enviro nmental factors on physicochemical properties of composts was in the order of pig manure amount>chicken manure amount>biogas residue amount and that on spectroscopic characteristics of composts was in the order of biogas residue amount>pig manure amount>chicken manure amount. Carbon-rich raw materials favor the maturation of compost. A high proportion of nitrogen-rich raw materials does not lead to the accumulation of ammonia in compost. A low proportion of biogas residue favors the formation of humic substances during the co-composting of biogas residue and livestock manure. In summary, the evaluation of compost fermentation effect should synthetically consider physic-chemical, biological indicators and spectral parameters instead of a single index. PMID- 26672308 TI - [Preliminary Research on Bubble Characteristics of Ancient Glaze Using OCT Technology]. AB - The bubble is one of the most common feature in ancient glaze. The size and distribution of bubbles are closely associated with recipes of the raw materials for the body and glaze and the making process. To characterize the bubbles is essential for the study of ceramic production process, production places, times characteristics and so on. In order to explore the possibility of using the optical coherence tomography (OCT) imaging technology to characterize the bubbles and the bubble distribution characteristic in glaze of ancient porcelain, sweep frequency OCT imaging system is used to detect five different types ancient porcelain chips. According to the two dimensional sectional images and three dimensional tomographic images of the transparent layer of glaze obtained by the OCT imaging system, the two dimensional sectional images characteristics and three dimensional slices characteristics of the bubbles in glaze are studied. The bubble characteristics in the glaze and its possible causes that gases in the body of the ceramic overflow to the glaze layer in the firing process are comprehensively analyzed. Meantime, the size of bubble is calculated according to the two dimensional sectional images based on pixel, and the result is compared with the traditional microscopic test result. The bubble size, two dimensional sectional characteristics and three dimensional tomographic image characteristics of opaque glaze are also studied. Experimental results show that the bubble characteristics in glaze of different ancient porcelain chips are obvious difference, the result of the bubble size calculated based on pixel coincides with the result of the bubble size observed by traditional microscope with ten times magnification, slices of the body near the body-glaze binding region based on OCT imaging technology three dimensional tomography can effectively reflect the bubble characteristics in glaze. The measurement of using OCT imaging technology to characterize bubble characteristics of the glaze is proposed, and the feasibility and the validity of the measurement are certified, and the nondestructive detection of bubble characteristics in ancient porcelain glaze is realized. Especially for the analysis of bubble characteristics of opaque glaze, the OCT imaging technology overcomes the limitations of using the traditional microscope technology to study the distribution of bubble in glaze in the past, and provides a novel, reliable analysis method for the analysis of ceramic glaze bubble characteristics. PMID- 26672309 TI - [Measurement of Mole Ratio for Alkali Metal Mixture by Using Spectral Absorption Method]. AB - The ratio of alkali metal mixture is one of the most important parameters in gauge head belonging to the ultra-sensitivity inertial measurement equipment, which is required to detect precisely. According to the feature that ratio of alkali metal is related to alkali metal vapor density, the theory of optical depth is used to detect the ratio of alkali metal in the present article. The result shows that the data got by the theory of optical depth compared with empirical formula differs at three orders of magnitude, which can't ensure the accuracy. By changing the data processing method, model between spectral absorption rate and temperature in cell is established. The temperature in alkali metal cell is calibrated by spectral absorption rate. The ratio of alkali metal atoms in the cell is analyzed by calculating the alkali density with empirical formula. The computational error is less than 10%. PMID- 26672310 TI - [Effects of Temperature on the Preparation of Al/Zn3N2 Thin Films Using Magnetron Reactive Sputtering]. AB - The effects of substrate temperature on the plasma active species were investigated by plasma optical emission spectroscopy. With increasing substrate temperature, the characteristic spectroscopy intensity of the first positive series of N2* (B(3)Pig-->A(3)Sigmau(+)), the second positive N2* (C(3)Piu- >B(3)Pig), the first negative series N2(+)* (B(2)Sigmau(+)-->X(2)Sigmag(+)) and Zn* are increased. Due to the substrate temperature, each ion kinetic energy is increased and the collision ionization intensified in the chamber. That leading to plasma ion density increase. These phenomenons's show that the substrate temperature raises in a certain range was conducive to zinc nitride thin films growth. Zn3N2 thin films were prepared on Al films using ion sources-assisted magnetron sputtering deposition method. The degree of crystalline of the films was examined with X-ray diffraction (XRD). The results show that has a dominant peak located at 34.359 degrees in room temperature, which was corresponding to the (321) plane of cubic anti-bixbyite zinc nitride structure (JCPDS Card No35 0762). When the substrate temperature was 100 degrees C, in addition to the (321) reflection, more diffraction peaks appeared corresponding to the (222), (400) and (600) planes, which were located at 31.756 degrees , 36.620 degrees and 56.612 degrees respectively. When the substrate temperature was 200 degrees C, in addition to the (321), (222), (400) and (600) reflection, more new diffraction peaks also appeared corresponding to the (411), (332), (431) and (622) planes, which were located at 39.070, 43.179 degrees , 47.004 degrees and 62.561 degrees respectively. These results show the film crystalline increased gradually with raise the substrate temperature. XP-1 profilometer were used to analyze the thickness of the Zn3N2 films. The Zn3N2 films deposited on Al films in mixture gas plasma had a deposition rate of 2.0, 2.2, and 2.7 nm . min(-1). These results indicate that the deposition rate was gradually enhanced as substrate temperature increased. Field emission scanning electron microscope (SEM) images revealed that the particles of zinc nitride thin films became smaller but more uniform and density with increase the substrate temperature. The Zn3N2 thin films were strongly bound on the Al films. The experiments of films properties analysis results about the substrate temperature were consistent with the results of the plasma optical emission spectroscopy. The results would help improving the preparation of magnetron sputtering technique and getting better Zn3N2 thin films. On the other hand, the results were reflected that the plasma emission spectrum was fast and effective method to analyze the intrinsic characteristics of plasma. PMID- 26672311 TI - [Synthesis and Properties of 1,11,15,25-Tetrahydroxy-4,8,18,22-Di (Bridged Dipropionate Carboxyl) Phthalocyanine Copper]. AB - In this dissertation, we study the synthesis and character of new substituted Phthalocyanine. Due to the widely application of Pcs in the fields, such as the communication, medical treatment, chemical industry and so on, therefore, they have been a hot topic over several decades by scientists. Nowadays, scientists have prepared thousands of Pcs and their derivatives. However, along with the human society development and the progress in science and technology, the new phthalocyanine with novle characteristics are still the goal of the scientists. In this dissertion, the synthetic methods of the phthlocyanine is improved. The synthesis and characterization of 1,11,15,25-tetrahydroxy-4,8,18,22-di(bridged dipropionate carboxyl) phthalocyanines are reported in this paper. The mixtures of malonic acid and 3,6-dihydroxy-phthalonitrile was added to water under stiriing. Then, a catalyst amount of sulfuric acid was added. The first synthetic precursor, i. e., malonic acid 3,3'-bis(6-hydroxy phthalonitrile) butter, its molecular formula is C19H8N4O6. phthalocyanines was prepared by malonic acid 3,3' bis(6-hydroxy phthalonitrile) butter and dihydrate zinc acetate, copper acetate monohydrate in n-amyl alcohol, using DBU as a catalyst under the 135 degrees C, molecular formula of phthalocyanine complexes is C38H16N8O12M. The product was characterized by Ultraviolet-visible (UV/Vis) Spectrum absorption and fluorescence, The results are agreement with the proposed structures. And electrochemical properties were studied. PMID- 26672312 TI - [Simultaneous Detection of External and Internal Quality Parameters of Huping Jujube Fruits using Hyperspectral Imaging Technology]. AB - Nondestructive detection of external and internal quality parameters of jujube is crucial for improving jujube's shelf life and industry production. Hyperspectral imaging is an emerging technique that integrates conventional imaging and spectroscopy to acquire both spatial and spectral information from a sample. It takes the advantages of the conventional RGB, near-infrared spectroscopy, and multi-spectral imaging. In this work, hyperspectral imaging technology covered the range of 450~1000 nm has been evaluated for nondestructive determination of "natural defects" (shrink, crack, insect damage and peck injury) and soluble solids content (SSC) in Huping jujube fruit. 400 RGB images were acquired through four different defect (50 for each stage) and normal (200) classes of the Huping jujube samples. After acquiring hyperspectral images of Huping jujube fruits, the spectral data were extracted from region of interests (ROIs). Using Kennard-Stone algorithm, all kinds of samples were randomly divided into training set (280) and test set (120) according to the proportion of 3:1. Seven principal components (PCs) were selected based on principal component analysis (PCA), and seven textural feature variables (contrast, correlation, energy, homogeneity, variance, mean and entropy) were extracted by gray level co-occurrence matrix (GLCM). The least squares support vector machine (LS-SVM) models were built based on the PCs spectral, textural, combined PCs and textural features, respectively. The satisfactory results show the correct discrimination rate of 92.5% for the prediction samples, as well as correlation coefficient (Rp) of 0.944 for the prediction set to calculate SSC content based on PCs and textural features. The study demonstrated that hyperspectral image technique can be a reliable tool to simultaneous detection of external ("natural defects") and internal (SSC) quality parameters of Huping jujube fruits, which provided a theoretical reference for nondestructive detection of jujube fruit. PMID- 26672313 TI - [Research and Application of the ICP-MS Detection Technology for the Content of Nb and Ta in Geochemical Sample]. AB - In order to provide the test analysis technology to support the exploration and development of niobium and tantalum resource, based on the special chemical properties of Nb and Ta in geochemical sample, we studied the detection methods for the content of Nb and Ta in geochemical sample by using inductively coupled plasma mass spectrometry (ICP-MS). The results show that the sample dissolution and instrumental parameter of ICP-MS, especially the former have significant influence? on detection results. Therefore, optimizing important parameters of sample dissolution is the key of the detection technology. The optimal parameters are that the weight of sample is 50 mg; the dosage of HF acid is 15 mL; the concentration of nitric acid and tartaric acid in the sample solution is 2% and 1.5%, respectively; the validity period of detection for sample solution <=1 d. The detection method has been validated by the national geochemistry standard reference material. The precise and exaction of method meet the required of industry standards. The detection limits of method for Nb and Ta are 1.05 and 0.13 MUg . g(-1), respectively. The experiment proved that the ICP-MS detection methods, which using certain preparation process of sample solutions, is suitable for accurate and rapid determination of Nb and Ta in geochemical sample, especially geochemical survey samples which with a large amount and low content of Nb and Ta. PMID- 26672314 TI - [Investigation of Cu Concentration in the CuSO4 Solution by Laser Induced Breakdown Spectroscopy]. AB - In this paper, the concentration of copper element in the CuSO4 solution was measured by Laser Induced Breakdown Spectroscopy with aqueous jets. We used the CuSO4 solution with 7 kinds of concentration and adopted statistical exploratory data analysis method to get calibration curve of Cu, whose linear fitting coefficient R2 was larger than 0.98. The average RSD of LIBS was 6.96%, and the average LOD of Cu was determined to be 12 ppm. The values of relative error by analyzing Cu I 324.75 nm and Cu I 327.40 nm spectral lines were respectively 6.52% and 5.86%, with the method called leave-one-out cross validation. The experimental relative error had a greater value, which was 10.3%, when the concentration of Cu was 10 ppm. However, the relative error decreased to 1.1% for the concentration of 2000 ppm, which indicated that LIBS need to be studied on its accuracy further in detecting lower analytical concentrations. LIBS has the promising application in detecting heavy metal elements in the environmental wastewater pollution. PMID- 26672315 TI - [Determination of Total Iron and Fe2+ in Basalt]. AB - Basalt is the raw material of basalt fiber. The content of FeO and Fe2O3 has a great impact on the properties of basalt fibers. ICP-OES and dichromate method were used to test total Fe and Fe(2+) in basalt. Suitable instrument parameters and analysis lines of Fe were chosen for ICP-OES. The relative standard deviation (RSD) of ICP-OES is 2.2%, and the recovery is in the range of 98%~101%. The method shows simple, rapid and highly accurate for determination of total Fe and Fe(2+) in basalt. The RSD of ICP-OES and dichromate method is 0.42% and 1.4%, respectively. PMID- 26672316 TI - [Spectroscopic Research on Slag Nanocrystal Glass Ceramics Containing Rare Earth Elements]. AB - The research group prepared the high-performance slag nanocrystal glass ceramics by utilizing the valuable elements of the wastes in the Chinese Bayan Obo which are characterized by their symbiotic or associated existence. In this paper, inductively coupled plasma emission spectroscopy (ICP), X-ray diffraction (XRD), Raman spectroscopy (Raman) and scanning electron microscopy (SEM) are all used in the depth analysis for the composition and structure of the samples. The experiment results of ICP, XRD and SEM showed that the principal crystalline phase of the slag nanocrystal glass ceramics containing rare earth elements is diopside, its grain size ranges from 45 to 100 nm, the elements showed in the SEM scan are basically in consistent with the component analysis of ICP. Raman analysis indicated that its amorphous phase is a three-dimensional network structure composed by the structural unit of silicon-oxy tetrahedron with different non-bridging oxygen bonds. According to the further analysis, we found that the rare earth microelement has significant effect on the network structure. Compared the nanocrystal slag glass ceramic with the glass ceramics of similar ingredients, we found that generally, the Raman band wavenumber for the former is lower than the later. The composition difference between the glass ceramics and the slag nanocrystal with the similar ingredients mainly lies on the rare earth elements and other trace elements. Therefore, we think that the rare earth elements and other trace elements remains in the slag nanocrystal glass ceramics have a significant effect on the network structure of amorphous phase. The research method of this study provides an approach for the relationship among the composition, structure and performance of the glass ceramics. PMID- 26672317 TI - [Decomposition of X-Ray Fluorescence Overlapping Peaks Based on Statistical and Genetic Algorithms]. AB - In fluorescence analysis, the phenomenon of overlapping often occurs among adjacent peaks. In the view of the random physical properties of formation process of X fluorescence spectra, Gaussian Mixture Statistics Model (GMSM) and Genetic Algorithms were used for the decomposition of overlapping peaks. First, the GMSM was proposed to describe the overlapping peaks, and the local convergence problem of expectation maximization (EM) was analyzed. Secondly, the GMSM parameters were regarded as individual genes, and the log-likelihood function of overlapping peaks random data was set as fitness function. A fast algorithm for the objective function value was proposed. Finally, the population search technology of Genetic Algorithm was used to find the global optimal solution, and to realize the decomposition of overlapping peaks. All measured data were regarded as "useful" data. The "useful" degree was reflected by their probability. The GMSM method can achieve the "best match" effect in the maximum global probability with zero loss of original data, which can fit the random of radiation measurement process. The decomposition experiments of four serious overlapping peaks show high precision of the peak position, peak area and standard deviation. The maximum error was 0.7 channel, 2.3% and 2.17%, respectively, which is especially suitable for the condition of serious overlap and can be widely used for the decomposition of other energy spectrum. PMID- 26672318 TI - [Time-Resolved XEOL Experiment System on BL14W1 at SSRF]. AB - A novel time-resolved X-ray excited optical luminescence (TRXEOL) experiment system was developed for X ray absorption fine structure spectroscopy(XAFS) beamline at Shanghai Synchrotron Radiation Facility (SSRF). The TRXEOL system is composed of three parts: timing system, spectrometer system and nuclear instrument module (NIM) system. These three systems were integrated to measure and record the optical luminescence from the sample excited by the synchrotron X ray pulses, according to the time-correlated single photon counting methodology. It's the first time in the domestic synchrotron radiation facilities to achieve TRXEOL experiment using the synchrotron X-ray pulses and the time structure of the storage ring. In this work, a SSRF-self-developed timing system was used, which is based on the Field programmable Gate Array and the high-speed serial communication technology. The timing system can provide trigger pulse synchronized with the X-ray pulse. The timing jitter is about 6 ps, and the timing delay resolution is 5 ps. The NIM system is the core of the TRXEOL experiment system, it has three main modules: the Constant Fraction Discriminator (CFD), the Time to Amplitude Converter (TAC) and the Multi-Channel Analyzer (MCA). During one excitation circle, the spectrometer and the Photomultiplier Tube detector translate the induced luminescence of the sample excited by a single X-ray pulse into electrical pulse. The CFD module eliminates the timing walk larger than 50 ps induced by the amplitude of the electrical pulse. The TAC module calculates the time interval between the timing trigger pulse and the luminescence electrical pulse, and converts the interval into proportional amplitude of voltage. After plenty of circles, the MCA module gets the luminescence decay curve by recording and analyzing the voltage signals. And the data acquisition system gets the TRXEOL spectra by scanning the spectrometer and acquiring the frequency of the voltage pulses from the TAC module. The TRXEOL experiment system helps researchers measure optical decay curves and spectra of the sample in different time windows. Many luminescence behaviors would be explained more deeply, together with the aid of the optical XAFS to get the electron structure of the sample. A sample of ZnO nanowire was studied using the TRXEOL system. The ordinary XEOL spectrum obtained could distinguish the 390 nm wavelength and the 500 nm wavelength luminescence center. The decay curve at 0 nm wavelength could clearly show the fast luminescence process and the slow luminescence process. The full width at half maximum of the fast luminescence decay curve was about 0.5 ns, showing that the minimum time resolution of the TRXEOL system is less than 1 ns. The TRXEOL spectra obtained could respectively get the luminescence information within different time windows. It was demo nstrated that the TRXEOL system is not only feasible and reliable, but also supply XAFS beamline with the technical preparatio ns of time resolved techniques. PMID- 26672319 TI - [A Comparison of Arsenic Speciation in 13 Pteris vittata L. Populations]. AB - Synchrotron radiation X-ray absorption near edge structure was employed to study the arsenic (As) speciation in 13 Pteris vittata L. populations collected from 7 provinces, cities, and autonomous regions in China. As in roots of P. vittata was mainly combined with oxygen (O), with a small amount of As combined with glutathione (GSH). Populations from Hunan and Guangxi provinces showed higher percentages of As-GSH in soots. As in roots of P. vittata was predominated with As(V), with the percentage of As(V) to the total As being 59.6+/-0.6%~83.8+/ 3.8%. The As(V) percentage was in the order of HN5HN3>HN1>TW>CQ>AH>FJ>HN5>HN2>GX2>GX3>HN4>GX1, within the range of 2.4%~12.9%. Different from that in roots, As in shoots was predominated with As(III), with no As(V) detected. The disclosure of As speciation in the roots and shoots of P. vittata contributes to the future research on As accumulation mechanism. PMID- 26672320 TI - [Spectral Analysis of Trace Fluorine Phase in Phosphogypsum]. AB - Phosphogypsum, which contains more than 90% of the calcium sulfate dehydrate (CaSO4 . 2H2O), is a kind of important renewable gypsum resources. Unlike the natural gypsum, however, phosphorus, fluorine, organic matter and other harmful impurities in phosphogypsum limit its practical use. To ascertain the existence form, content and phase distribution of trace fluoride in phosphogypsum has important theoretical values in removing trace fluoride effectively. In this present paper, the main existence form and phase distribution of trace fluoride in phosphogypsum was investigated by the combination of X-ray photoelectron spectroscopy (XPS) and Electron microprobe analysis (EMPA). The results show that trace fluoride phase mainly includes NaF, KF, CaF2, K2SiF6, Na2SiF6, Na3AlF6, K3AlF6, AlF3 . 3H2O, AlF2.3(OH)0.7 . H2O, Ca5(PO4)3F, Ca10(PO4)6F2. Among them, 4.83% of fluorine exists in the form of fluoride (NaF, KF, CaF2); Accordingly, 8.43% in the form of fluoride phosphate (Ca5(PO4)3F, Ca10(PO4)6F2); 12.21% in the form of fluorine aluminate (Na3AlF6, K3AlF6); 41.52% in the form of fluorosilicate (K2SiF6, Na2SiF6); 33.02% in the form of aluminum fluoride with crystal water (AlF3 . 3H2O, AlF2.3(OH)0.7 . H2O). In the analysis of phase constitution for trace elements in solid samples, the method of combining XPS and EMPA has more advantages. This study also provides theoretical basis for the removal of trace fluorine impurity and the effective recovery of fluorine resources. PMID- 26672321 TI - [Automatic Recognition of Overlapped Spectral Peaks by Combined Symmetric Zero Area Conversion and L-M Fitting]. AB - The peaks' overlapping often exists in Raman spectroscopy analysis, because of the low spectral resolution of the spectrograph and the complex sample components. The overlapped peaks lead to the errors in peak parameters extraction easily, and at last lead to the analysis error of sample components, which increases the difficulty in automatic analysis of field spectra. The identification of overlapped peaks is the key difficulty of in-situ spectra analysis. To solve this problem, an automatic method of identifying the overlapped peaks was established basing on an analysis model with multiple Gaussian shape peaks. The peak number and the initial parameters(the peak position, peak height, and width) were obtained by symmetric zero-area transformation firstly, and then the parameters were optimized by Levenberg Marquardt fitting method eventually. Some algorithm experiments were executed to test the method respectively by simulated data and Raman spectra data, and the former showed that the symmetric zero-area transformation method can extract the initial peak parameters with high accuracy, and then converges fast, and is adaptive to signal with wide dynamic range of SNR, but has false and omissive peaks to low SNR signal. The research results show that the automatic method of identifying the overlapped peaks with symmetric zero-area transformation combined with L-M fitting has a certain practical value. PMID- 26672322 TI - [Moving Mirror Scanning System Based on the Flexible Hinge Support]. AB - In order to improve moving mirror drive of Fourier transform infrared spectrometer, we design a dynamic scanning system based on flexible hinge support. Using the flexible hinge support way and the voice coil motor drive mode. Specifically, Using right Angle with high accuracy high stability type flexible hinge support mechanism support moving mirror, dynamic mirror can be moved forward and backward driven by voice coil motor reciprocating motion, DSP control system to control the moving mirror at a constant speed. The experimental results show that the designed of moving mirror scanning system has advantages of stability direction, speed stability, superior seismic performance. PMID- 26672323 TI - [Calibration Method for the Monochromator Based on Continuous Spectrum Light Source]. AB - For the inevitable errors of the monochromator in the process of producing and installing, it must be calibrated before being used. For the traditional calibration method using mercury lamp, the number of wavelengths limits the calibration precision of the monochromator. Based on the principle of grating monochromator, calibration method for the monochromator based on continuous spectrum light source is proposed. Calibration system is designed and built, which is composed of broadband light source using tungsten halogen lamp, power source, light filter, the monochromator, spectroscopy to detect the intensity of the monochromator output, and computer. Divide the intensity detected on the output of monochromator by the intensity detected directly the tungsten halogen lamp. The result is the transmissivity function of the monochromator eliminating the influence of the halogen tungsten lamp radiation and the spectrometer response function. On a certain dial number, the transmissivity function is measured, normalized and the peak wavelength is calculated. 22 groups of wavelength data and dial number are acquired. 8, 14, 18, 22 points are chosen separately to calibrate the relationship between the wavelength and the dial number of monochromator by linear fitting and quadratic fitting. Experimental results show the calibration result in 22 points is better than others, (8 points similar to the calibration method using mercury lamp). The result of quadratic fitting with 22 points as the final result is better than linear fitting. So the calibration method for monochromator using the continuous spectrum light source with more calibration points is superior to the traditional calibration method using mercury lamp. PMID- 26672324 TI - [Research on Assessment Methods of Spectrum Data Quality of Core Scan]. AB - Core scan is the instrument used for core spectrum and pictures detection that has been developed in recent years. Cores' data can be digitized with this equipment, then automatic core catalog can be achieved, which provides basis for geological research, mineral deposit study and peripheral deposit prospecting. Meanwhile, an online database of cores can be established by the means of core digitalization to solve the cost problem caused by core preservation and share resources. Quality of core data measurement directly affects the mineral identification, reliability of parameter inversion results. Therefore it's very important to quasi-manage the assessment of data quality with the instrument before cores' spectrum testing services. Combined with the independent R&D of CSD350A type core scan, and on the basis of spectroscopy basic theory, spectrum analysis methods, core spectrum analysis requirements, key issues such as data quality assessment methods, evaluation criteria and target parameters has been discussed in depth, and comprehensive assessment of independent R&D of core scan has been conducted, which indicates the reliability and validity of spectrum measurements of the instrument. Experimental tests show that the methods including test parameters and items can perfectly response the measurements of reflectance spectrum, wavelength accuracy, repeatability and signal to noise ratio with the instrument. Thus the quality of core scan data can be evaluated correctly, and the foundation of data quality for commercial services can be provided. In the case of the current lack of relevant assessment criteria, the method this study proposes for the assessment has great value in the work of core spectrum measurements. PMID- 26672325 TI - [Biological Process Oriented Online Fourier Transform Infrared Spectrometer]. AB - An online Fourier Transform Infrared Spectrometer and an ATR (Attenuated Total Reflection) probe, specifically at the application of real time measurement of the reaction substrate concentration in biological processes, were designed. (1) The spectrometer combined the theories of double cube-corner reflectors and flat mirror, which created a kind of high performance interferometer system. The light path folding way was utilized to makes the interferometer compact structure. Adopting double cube-corner reflectors, greatly reduces the influence of factors in the process of moving mirror movement such as rotation, tilt, etc. The parallelogram oscillation flexible support device was utilized to support the moving mirror moves. It cancelled the friction and vibration during mirror moving, and ensures the smooth operation. The ZnSe splitter significantly improved the hardware reliability in high moisture environment. The method of 60 degrees entrance to light splitter improves the luminous flux. (2) An ATR in situ measuring probe with simple structure, large-flux, economical and practical character was designed in this article. The transmission of incident light and the light output utilized the infrared pipe with large diameter and innerplanted high plating membrane, which conducted for the infrared transmission media of ATR probe. It greatly reduced the energy loss of infrared light after multiple reflection on the inner wall of the light pipe. Therefore, the ATR probe obtained high flux, improved the signal strength, which make the signal detected easily. Finally, the high sensitivity of MCT (Mercury Cadmium Telluride) detector was utilized to realize infrared interference signal collection, and improved the data quality of detection. The test results showed that the system yields the advantages of perfect moisture-proof performance, luminous flux, online measurement, etc. The designed online Fourier infrared spectrometer can real-time measured common reactant substrates such as glycerin in the bioreactor under high quality. There is a large potential market, such as online analysis in biological, chemical testing and material analysis. PMID- 26672326 TI - [A New Strategy of Spectrum and Polarization Measuring based on LCVR and AOTF]. AB - In view of the existing relatively cumbersome polarization measurement method of using liquid crystal phase variable retarder (LCVR) and acousto-optic tunable filter (AOTF), a new strategy of spectrum and polarization measurement is put forward. This method removed mechanical movement and reduced the amount of phase delay from four groups to two groups. This method realizes the spectrum and polarization measurements by measuring the plus and minus 1 level diffraction light of the system with two LCVR, one AOTF and two same version detectors. For the polarization measurement of a particular wavelength, the computer controlled LCVR driving voltage to achieve the required phase delay in accordance with the requirements of the wavelength, it also controlled the driving frequency to implement the required wavelength selection of AOTF. Because of the different driving frequencies of AOTF corresponding to the different wavelengths, so it can get the spectral information by scanning the whole frequency bands, In this paper detailed principles are deduced and the polarization model of AOTF is analyzed, it also deduced the measurement formula of I, Q, U in the corresponding Stokes parameter through the theoretical calculation Muller matrix of the LCVR and AOTF. Finally it analyzed and simulated the measurement error of the whole system which was caused by the tiny deviation of phase delay, the simulation results show that relative error <3% when the phase delay amount within the range of +/-pi/100. This experiment proved the feasibility and accuracy of the measurement system, the results show that the error of the measuring system overall <6%. This study provides a new method of polarization measurement which is simple, feasible and precise, it has important application value. PMID- 26672327 TI - [Correlation of Allelopathy of Rehmannia glutinosa Root Exudates and Their Phenolic Acids Contents]. AB - OBJECTIVE: To study the allelopathic potential of Rehmannia glutinosa root exudates in different growth stages and dynamic change of phenolic acids contents, in order to reveal the correlation between phenolic acids and allelbpathy effect of Rehmannia glutinosa. METHODS: Root exudates of Rehmannia glutinosa in different growth stages were obtained by a new instrument which was used to collect the root exudates of xerophytes. After that, bioassay was applied to estimate allelopathy effect of the root exudates. HPLC was used to determine the contents of five phenolic acids (coumaric acid, 4-hydroxybenzoic acid, vanillic acid, syringic acid and ferulic acid) which were reported to relate to allelopathy effect. Correlation of bioassay data and HPLC data were also analyzed. RESULTS: The germination rate of radish after soaking by root exudates of different growth stages of Rehmannia glutinosa was 97. 89%, 92. 38%, 89. 52%, 85. 71%, 85. 71%, 84. 76% and 83. 81%, respectively, which indicated a decline trend. And significant differences were shown from previous enlargement stage compared with the contrast. The bud length after soaking by root exudates was 5. 68, 5. 76, 5. 91, 5. 65, 5. 41, 5. 28 and 5. 11 cm, separately, which increased slightly before decreasing gradually. Previous enlargement stage was also the initial period when significant differences were shown. Five phenolic acids were detected in root exudates by HPLC, while the change of their contents and the allelopathy effect of root exudates did not perform a similar trend. Correlation analysis indicated the five phenolic acids did not have significant relevance (r = - 0. 666 - 0. 590) with germination rate and bud length of radish except the negative correlation (r = -0. 833, P <0. 05) of syringic acid and bud length. CONCLUSION: Significant allelopathy effect of Rehmannia glutinosa is performed from previous enlargement stage and enhanced with its growth. Syringic acid is a probable dominant allelochemical of Rehmannia glutinosa. PMID- 26672328 TI - [Quadratic Orthogonal Rotation Combination Design on Alisma orientalis of Fertilization]. AB - OBJECTIVE: To study the effects of combined N, P, K and micronutrient fertilizers on the yield of Alisma orientalis tuber, and to optimize the fertilizer application rate. METHODS: Four factors five levels quadratic orthogonal rotation combination design was used. A function was established on nitrogen, phosphor, potassium and microelement fertilizer application rate with the yield of Alisma orientalis tuber. RESULTS: The established mathematical model was of high reliability for prediction with quadratic regression equation of R2 = 0. 8980. The order of increasing Alisma orientalis tuber yield was nitrogen > micronutrient fertilizer > potassium > phosphor. The results of the frequency analysis showed that for the target yield over 8 250 kg/hm2 and the confidence interval of 95%, the optimal fertilizer application rates were as follows :nitrogen of 241. 45 - 283. 55 kg/hm2, phosphor of 81. 14 - 208. 44 kg/hm2, potassium of 95. 57 - 239. 42 kg/hm2, and zinc fertilizer of 14. 32 - 16. 18 kg/hm2, boron fertilizer of 18. 84 - 19. 86 kg/hm2, and molybdenum fertilizer of 0. 151 -0. 159 kg/hm2 in micronutrient fertilizer. CONCLUSION: Nitrogen is related to the growth of Alisma orientalis, potassium promotes tuber bulking, micronutrient fertilizer consisted of zinc, boron and molybdenum fertilizer promotes Alisma orientalis growth and the absorption of nitrogen, phosphor and potassium. Moderate application of nitrogen, phosphorus, potassium, zinc, boron and molybdenum fertilizer can promote Alisma orientalis tuber yield. The nitrogen has the best effect. PMID- 26672329 TI - [Comparative Analysis of Different Inonotus obliquus]. AB - OBJECTIVE: To screen optimal Inonotus obliquus strains that is suitable to cultivation, extracting effective components on industrialized production, genetics and breeding. METHODS: Inonotus obliquus mycelia from different countries were used. High quality strain was screened by comparing the antagonism between Inonotus obliquus and penicillium. The contents of crude fat, crude ash, crude protein and crude fiber were analyzed. RESULTS: It was showed that antagonism ability of Finnish birch was the strongest, its mycelia diameter was up to 53. 27 mm. It was also showed that nutritional ingredient was abundant in artificial cultured Inonotus obliquus strains. The contents of crude fat and crude protein in Finnish birch were higher, which was 1. 93% and 20. 23%, respectively. The contents of crude fat and crude protein in NBRC8681 strains were lower, which was 1. 55% and 19. 85%, respectively. The content of crude ash of JL04 strains was higher(8. 76%). The content of crude ash of NBRC8681 strains was lower(6. 8%). Crude fiber content was higher in HLJ01 strains, its content reached to 45. 09%. The least content appeared in MAFF420101 strains, whose crude fiber content was only 38. 27%. CONCLUSION: The strains of Finnish birch, HLJ01 and JL04 are suitable to exploitation. PMID- 26672330 TI - [Effect of Basic Soil Nutrients and Inorganic Elements on Quality of Pseudostellaria heterophylla Root]. AB - OBJECTIVE: To study the effect of basic soil nutrients and inorganic elements on the quality of Pseudostellaria heterophylla root, in order to reveal the inner link and to provide the scientific basis for rational cultivation of Pseudostellaria heterophylla. METHODS: The medicinal materials of Pseudostellariae Radix and soil samples from 15 habitats were collected, and three essential nutrients, five inorganic elements in the soil and the medicinal contents of polysaccharides and pseudostellarin B were determined. Then using SPSS software to analyze its relevance. RESULTS: Significant difference of pseudostellarin B content was found in samples from different provinces, which was not detected in the sample of Fujian Province, but the difference of polysaccharides content was small, at around 30%. Basic nutrients and inorganic elements from the soil for comparison, Pseudostellaria heterophylla from different habitats and cultivation of soil nutrients and inorganic elements contents were very uneven. The contents of Pb, Cu and B in the soil sample of Guizhou Province were the highest, and Cr and available phosphorus content in the soil sample of Shandong Province, Zn and effective potassium in the soil sample of Fujian Province all were the highest. With reference to the Soil Environment Quality Standard (GB15618-1995), most of Pseudostellaria heterophylla soil reached the national standard. From the point of soil elements and medicinal materials quality correlation, pseudostellarin B content and polysaccharide content had no significant correlation between each element in the soil. CONCLUSION: The ammonium nitrogen, effective potassium, available phosphorus and elements of Pb, Cr, Cu, Zn and B in the soil have no direct effect on effective component content of medicinal materials. 60% of Pseudostellaria heterophylla origin is generally lack of B in soil. It should be appropriate to increase the percentage of boron in the fertilizer management to ensure the quality of Pseudostellaria heterophylla root. PMID- 26672331 TI - [Chemical Constituents of Armadillidium vulgare]. AB - OBJECTIVE: To study the chemical constituents of Armadillidium vulgare. METHODS: Compounds were isolated and purified by various column chromatography, spectroscopic methods were used to identify their structures. RESULTS: Seven compounds were isolated from Armadillidium vulgare and identified as vulgarine A (1), o-hydroxylbenzoic acid (2), dipyrrolopiperazine-2,5-dione (3), 4(1-H) quinolone (4), adenine (5), n-acetyltyramine (6) and 4-methyl-5-thiazoleethanol (7). CONCLUSION: Compound 1 is a new alkaloid, compounds 3-7 are all nitrogen containing substances, which are isolated from Armadillidae family for the first time. PMID- 26672332 TI - [Determination of Amino Acids in Pearl Powder and Conch Powder from Different Origins by HPLC with Pre-column Derivation]. AB - OBJECTIVE: To establish an analysis method for determination of amino acids in pearl powder and conch powder from different origins by HPLC with pre-column derivation. METHODS: Hydrolytic amino acids were extracted by acid hydrolysis method,then derivatized with phenyl isothiocyanate (PITC). And the samples were analyzed on a C, column with gradient elution of 0.1 mol/L sodium acetate solution (adjusted to pH 6. 5) (A) and acetonitrile (B) at the flow rate of 1. 0 mL/min. The detected wavelength was 254 nm. RESULTS: Amino acids derivative solution remained stable in 24 hours. The response was linear for seven amino acids with a correlation coefficient r >0. 9995. The average recoveries were 93. 16% - 103. 31%. CONCLUSION: The method is sensitive with good accuracy and repeatability, which is useful for the determination of amino acids in pearl powder and conch powder from differei origins. PMID- 26672333 TI - [Study on Commercial Specification of Lonicerae Japonicae Flos]. AB - OBJECTIVE: To provide the basis data for the institute of commercial specification standard of Lonicerae Japonicae Flos. METHODS: 39 samples of Lonicerae Japonicae Flos commercial of different grades in market were collected, and vernier caliper and electronic balance were used to measure the numbers of flower bud and blooming rate per 0. 5 g, contamination content, browning degree, milden and rot, length, upside diameter, middle diameter and bottom diameter of Lonicerae Japonicae Flos. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, galuteolin,3,5-icaffeoylquinic acid and 4,5 dicaffeoylquinic acid were detected by HPLC. Correlation analysis, principal component analysis and cluster analysis were used by SPSS to analyze all index data,and the correlation of appearance characteristics and intrinsic active constituents was discussed. RESULTS: The numbers of flower bud and blooming rate per 0. 5 g, contamination content and browning degree were principal component indexes. The length of flower bud showed a significant correlation with galuteolin content, and the browning degree and upside diameter showed a significant correlation with chlorogenic acid content. CONCLUSION: Lonicerae Japonicae Flos commercial should be divided into four specification grades by sieved indexes. PMID- 26672334 TI - [Quality Suitability of Magnolia officinalis in China Based on GIS]. AB - OBJECTIVE: To study the quality suitability rank dividing of Magnolia officinalis on the basis of investigation on the correlation between the ratio of magnolol and honokiol in Magnoliae Officinalis Cortex and ecological factors, in order to provide scientific basis for its planting area of high-quality medicinal materials. METHODS: Based on the samples' quality analysis of 43 sampling points of Magnolia officinalis,the relationship between the ratio of magnolol and honokiol in Magnoliae officinalis Cortex and ecological factors was analyzed by statistical analysis. The geographic information system(GIS) was applied to assess the quality suitability rank dividing of Magnolia officinalis in China. RESULTS: There were 12 ecological factors mainly affecting the quality of Magnoliae Officinalis Cortex; The ratio of magnolol and honokiol had obvious characteristics of regional quality. Conclusion: Magnoliae Officinalis Cortex which produced in Hubei and Chongqing is dao-di herbs. PMID- 26672335 TI - [QTRAP LC-MS/MS Analytical Study on Nucleosides and Nucleobases of Pseudostellariae Radix Cultivated in Different Idioplasm Resources]. AB - OBJECTIVE: To analyze nucleosides and nucleobases of Pseudostellariae Radix cultivated in different idibplasni resources and to compare the differences. METHODS: QTRAP LC-MS/MS method was applied for the analysis of 13 kinds of nucleosides and nucleobases in Pseudostellariae Radix and the data obtained was analyzed by SPSS 16. 0 software. RESULTS: There were some differences between Pseudostellariae Radix cultivated in different idioplasm resources. The highest amount of nucleosides and nucleobases was ZS2 which came from Zherong in Fujian Province. The total content of nucleosides and nucleobases in the sample from Shibing in Guizhou Province was the lowest. There was little difference between ZS1 (Zherong in Fujian Province) and XC(Xuancheng in Anhui Province). CONCLUSION: This study provides evidence for the influence of eco-environment on the metabolites of Pseudostellariae Radix. PMID- 26672336 TI - [Analysis of Volatile Oils from Different Processed Products of Zingiber officinale Rhizome by GC-MS]. AB - OBJECTIVE: To analyze the volatile components in different processed products of Zingiber officinale rhizome, and to make clear the effect of different heating degree on them. METHODS: The volatile components were extracted from four kinds of processed products by applying steam distillation, and then were analyzed by GC-MS. RESULTS: There were totally 43 components of volatile oil identified from four kinds of processed products of Zingiber officinale rhizome. Fresh product, dried product, and charcoal product of Zingiber officinale rhizome each had 27 components of volatile oil, while sand fried product contained 24 components. Fresh Zingiber officinale rhizome contained 22. 59% of zingiberene, 20. 87% of a citral and 11. 01% of beta-phellandrene, respectively. After processing in different heating degree, the volatile components changed greatly in both of their quantity and quality, For instance, dried Zingiber officinale rhizome contained 40. 48% of alpha-citral and 8-phellandrene content was slightly lower at 10. 38%. 32.73% of 3,7,11-trimethyl-l, 6, 10-dodecatriene,16. 38% of murolan 3, 9 (11)-diene-10-peroxy and 3. 36% of cubebene newly emerged in the sand fried Zingiber officinale rhizome, and eudesm-4 (14) and beta-bisabolol, etc. However, beta-phellandrene content was only 1. 95%. The zingiberene and beta sesquiphellandrene were the highest in charcoal product, besides, new components such as alpha-cedrene, decanal and gamma-elemene appeared. CONCLUSION: Volatile components in different processed products of Zingiber officinale rhizome were different in both of their kinds and contents. This method is suitable for the analysis of volatile components in Zingiber officinale rhizome, and this study can provide the experimental evidence for quality evaluation and clinical application for ginger processed products. PMID- 26672337 TI - [Specific PCR Molecular Identification of Euconunmia Cortex]. AB - OBJECTIVE: To screen specific DNA sequence by rDNA-ITS sequence analysis at Eucommmia Cortex and its adulterants, then specific primers were designed to identify Eucommmia Cortex rapidly. METHODS: rDNA-ITS sequences of Eucommmia Cortex and its adulterants were downloaded from NCBI. The specific DNA sequence in the rDNA-ITS sequence of Eucommmia Cortex was found by compared with all sequences. Specific primers for authentic the Eucommmia Cortex were designed. PCR amplification and detection methods were optimized. RESULTS: PCR amplification products were detected through agarose gel electrophoresis and fluorescence reaction. The 400 bp identification band for Eucommmia Cortex could be produced and green fluorescent could be observed under ultraviolet light after adding the dye SYBR Green I. However its adulterants were without identification hand and green fluorescent. CONCLUSION: Specific PCR molecular identification can be applied to identify Eucommmia Cortex, the time is shortened significantly by PCR amplification optimization, and fluorescence detection can be more visually display the identification results. In a word, this study provides new ideas and methods for rapid identification of Eucommmia Cortex. PMID- 26672338 TI - [UPLC Fingerprint of Oldenlandia corymbosa]. AB - OBJECTIVE: To establish the UPLC fingerprint of Oldenlandia corymbosa from different regions and to distinguish it from Oldenlandia diffusa. METHODS: UPLC procedure was performed on an ACQUITY UPLC BEH C18 (50 mm x 2. 1 mm, 1. 7 um) column and eluted with a mobile phase consisted of methanol-l % acetic acid at a flow rate of 0. 2 mL/min. The column temperature was 30 degrees C . The detection wavelength was 254 nm. A matrix was constructed for similarity evaluation, cluster analysis and principle component analysis. RESULTS: The collected samples had a good similarity. A specificity fingerprint chromatogram was produced and 15 common peaks were designated. Samples were divided into four groups. CONCLUSION: It is a reliable and available method for specific identification of Oldenlandia corymbosa and for distinguishing Oldenlandia corynbosa and Oldenlandia diffusa. PMID- 26672339 TI - [Chemical Components from Leaves of Fatsia japonica and Their Antitumor Activities in vitro]. AB - OBJECTIVE: To study the chemical components from the leaves of Fatsia japonica and their antitumor activities in vitro. METHODS: All compounds were separated and purified by column chromatography over silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified by physical and chemical properties and spectral methods including 1H-NMR and 13C-NMR. Antitumor assay was measured by MTT method. RESULTS: 18 compounds were isolated and identified as palmitic acid (1), beta-hydroxypropiovanillone (2), adenosine (3), beta sitosterol (4), daucosterol (5), oleanolic acid (6), echinocystic acid (7), betulinic acid (8), hederagenin(9), hederagenin-3-O-alpha-L-rhamnopyranosyl(1- >2)-alpha-L-arabinopyranoside(10), acacetin(11), quercetin(12), quercetin-3-O beta-D-glucopyranoside(13), isovitexin(14), isovitexin-7-O-glucoside(15), astragalin(16), methylpluviatolide(17), and syringaresinol-4-O-beta-D glucopyranoside(18). CONCLUSION: All compounds are isolated from the leaves of Fatsia japonica for the first time except compound 1. The ethyl acetate extract and compounds 6, 10, 12 and 18 at the concentration of 0. 5 mg/mL showed inhibitory effect against the proliferation of colon cell line A549 with the inhibitory rate over 90% in vitro. PMID- 26672340 TI - [Chemical Constituents of Ethyl Acetate Fraction of Suaeda glauca]. AB - OBJECTIVE: To study the chemical constituents of Suaeda glauca. METHODS: The chemical constituents were isolated and purified with several separation and purification techniques. Their structures were identified by physicochemical properties and various spectroscopic methods. RESULTS: Ten compounds were isolated from the ethyl acetate fraction as lignoceric acid (1), beta-amyrin-n nonyl ether(2), beta-sitosterol(3), beta-daucosterol(4), quercetin(5), luteolin(6), luteolin-7-O-beta-D-glucoside(7), isorhamnetin(8), scopoletin (9) and stigmasterol(10). CONCLUSION : Compounds 1, 2, 6, 7, 8, 9 and 10 are isolated from Suaeda genus for the first time and compounds 3 - 5 are isolated from this plant for the first time. PMID- 26672341 TI - [Chemical Constituents from Syzygium samarangense Branches and Leaves]. AB - OBJECTIVE: To investigate the chemical constituents from the branches and leaves of Syzygium samarangense. METHODS: The dried branches and leaves of Syzygium samarangense were powdered and extracted with 95% ethanol, then partitioned with petroleum ether, chloroform and ethyl acetate. The chloroform fraction was subjected to silica gel, Sephdex L-20 and preparative HPLC. The structures were identified by physicochemical properties and spectral data. RESULTS: 14 compounds were respectively isolated and identified as ursolic aldehyde(1), betulin(2), betulinic aldehyde(3), betulinic acid(4), lupeol(5), beta-sitosterol(6), 5, 7 dihydroxy-6-methylflavanone(7), 2', 4'-dihydroxy-6'-methoxy-3' methyldihydrochalcone (8), 2', 4'-dihydroxy-6'-methoxy-3'-methylchalcone (9), 5, 7-dihydroxy-6, 8-dimethylflavanone (10), 5, 7-dihydroxyflavanone (11), 2', 4' dihydroxy-6'-methoxy-3', 5'-dimethyldihydrochalcone (12), 2'-hydroxy-4', 6' dimethoxy-3'-methylchalcone(13) and p-hydroxyb6nzaldehyde(14). CONCLUSION: Compounds 1 - 4 and 14 are isolated from this plant for the first time. PMID- 26672342 TI - [Study on Flavonoids in Buddleja lindleyana Fruits]. AB - OBJECTIVE: To study the flavonoids in the fruits of Buddleja lindleyana. METHODS: The compounds were separated by repeated silica gel, RP-18 and Sephadex LH-20. Their structures were elucidated on the basis of chemical evidence and spectral data. RESULTS: Five flavonoids were isolated and identified as luteolin (1), tricin (2), acacetin (3), acacetin-7-O-beta-D-glucopyranoside (4) and linarin(5). CONCLUSION: Compounds 3,4 and 5 are isolated from fruits of Buddleja lindleyana for the first time. Compound 2 is isolated from fruits of Buddleja lindleyana for the first time. PMID- 26672343 TI - [Chemical Constituents from Claoxylon indicum Stems]. AB - OBJECTIVE: To study the chemical constituents of Claoxylon indicum stems. METHODS: The chemical constituents were isolated, purified and identified by various chromatographic and spectral techniques. RESULTS: Seven compounds including oleanolic acid (1), 6-amyrin(2), 7-ketositosterol(3), scopoletin(4), beta-sitosterol-beta-glucoside(5), L-pyroglutamic acid (6) and beta-sitosterol (7) were isolated from ethanol extract of this plant stems. CONCLUSION: Compounds 1 - 6 are obtained from this plant for the first time. PMID- 26672344 TI - [Chemical Constituents from Mallotus paniculatus (II)]. AB - OBJECTIVE: To study the chemical constituents of Mallotus paniculaus radix. METHODS: The compounds were isolated with column chromatography. The chemical structures were identified by spectral and spectroscopic technology. RESULTS: Seven compounds were isolated from the n-BuOH extract and identified as scopoletin(1), isoscopletin(2), erythordiol(3), apigenin(4), 4-methoxybenzoic acid(5), acetylaleuritolic acid(6) and beta-daucosterol (7). CONCLUSION: compounds 2 - 6 are isolated from this plant for the first time. PMID- 26672345 TI - [Research on Biological Assessment for Panax notoginseng Quality on Real-time Cell Electronic Analysis]. AB - OBJECTIVE: To establish the quality control and evaluation methods of Panax notoginseng on promoting blood circulation and removing blood stasis effects, by determining cell index to evaluate the quality of Panax notoginseng from different habitats. METHODS: Using the real-time cell electronic analysis technology (RTCA) to examine the biological activity of specific cell-dependent cell lines on Panax notoginseng extracts. Changing trends and laws of the samples within a certain time were analyzed, and the cell index at the optimum time was determined. RESULTS: In four batches of Panax notoginseng from different habitats, cell index of Panax notoginseng from Chuxiong of Yunnan Province at the optimal time of 38 h was the highest, and the biological activity was the strongest. Cell index of Panax notoginseng from Wenshan of Yunnan Province at the optimal time of 38 h cells was the lowest, and the biological activity was the weakest. CONCLUSION: The method based on the real-time cell electronic analysis technology can initially be used in the detection of biological activity of Panax notoginseng. PMID- 26672346 TI - [Comparative Study on Quality of Volatile Oil of Acori Tatarinowii Rhizoma from Two Habitats]. AB - OBJECTIVE: To compare the quality of volatile oil of Acori Tatarinowii Rhizoma from Guangxi and Sichuan. METHODS: The volatile oil was extracted from Acori Tatarinowii Rhizoma by using steam distillation method, and analyzed by GC-MS. Peak area normalization method was used for calculating the relative percentage contents of chemical constituents, and hierarchical cluster analysis was used for classifying the 20 batches of samples by their relative contents of the main components that were methyleugenol, cis-methylisoeugenol, gamma-asarone, beta asarone and alpha-asarone. RESULTS: The average extraction rate of 10 batches of volatile oil in Acori Tatarinowii Rhizoma from Guangxi was 1. 61%, and 10 batches of samples from Sichuan was 1. 72%. The relative percentage contents of five main components totaled 78. 19% and 88. 84%, respectively. By t-test, there was no statistical difference between samples from Guangxi and Sichuan. In the hierarchical cluster analysis,10 batches of samples from Guangxi and 10 batches of samples from Sichuan could respectively be classified into four clusters subcategories and five clusters subcategories, while the mean of samples of Guangxi and the mean of samples of Sichuan respectively analyzed with 20 batches of the two habitats that all were classified in the same clusters subcategories. The results of similarity showed that the correlation coefficients of 8 batches in 10 batches of samples from Guangxi were over 0. 9, while 1 batch was only 0. 466. The correlation coefficients of 7 batches in 10 batches of samples from Sichuan had were over 0. 9, while 1 batch was only 0. 069. The correlation coefficients between the mean of samples of Guangxi and the mean of samples of Sichuan was 0. 996. CONCLUSION: Quality of the different batches of volatile oil from Acori Tatarinowii Rhizoma have significant differences, but it has no obvious correlation with the habitats. PMID- 26672347 TI - [Simulation and Prediction of Material Foundation of Rhei Radix et Rhizoma for Ischemic Stroke Based on Molecular Docking Technology]. AB - OBJECTIVE: To apply molecular docking technology for virtual screening of active molecules of Rhei Radix et Rhizoma, and to explore the effective substances. METHODS: 21 key targets proteins related with cerebral ischemia with 52 compounds of Rhei Radix et Rhizoma based on molecular docking technology were combined to select active small molecules. Meanwhile, multi-component protein target network was established by software Cytoscape 2. 8. 1. RESULTS: It was identified that 23 of those compounds had strong interactions with no less than 10 targets by virtual screening of molecular docking. CONCLUSION: The method of virtual screening based on molecular docking can be used to find the active components of Rhei Radix et Rhizoma in treatment of cerebral ischemia. It provides the reference for research on multi-targets of Chinese medicine compound. PMID- 26672348 TI - [Effects of Cordycepin on Proliferation, Apoptosis and NF-kappaB Signaling Pathway in A549 Cells]. AB - OBJECTIVE: To investigate the effects of Cordycepin on proliferation and apoptosis of A549 cells, and its possible mechanism of action. METHODS: Human lung cancer cell line A549 cells were treated with different concentrations of Cordycepin for 24 h. MTS assay was used to detect cell proliferation. Hoechst 33258 staining and Annexin V/PI flow cytometry were used to determine the apoptosis of A549 cells. The protein expression of nuclear factor-kappaB p65 (NF kappaB p65), BAX, BCL-2 and cleaved Caspase-3 was determined by Western blot. RESULTS: In a dose dependent way, Cordycepin inhibited the proliferation and promoted the apoptosis of A549 cells, increased the expression of BAX and cleaved Caspase-3, while decreased the expression of BCL-2. The Western blot results showed, Cordycepin dose-dependently inhibited the entry of NF-kappaB p65 to nuclear in A59 cells. CONCLUSION: Cordycepin can inhibit the proliferation and induct the apoptosis of A549 cells, the mechanism of action is achieved by inhibiting the NF-kappaB pathway. PMID- 26672349 TI - [Protective Effect of Saussurea involucrata Alcohol Extract on Liver Mitochondria in Mice Under Hypoxia Condition]. AB - OBJECTIVE: To study the protective effect of Saussurea involucrata alcohol extract on liver mitochondria in mice under hypoxia condition. METHODS: The hypoxia mice model was established, the BALB/c mice were randomly divided into four groups:normal group ,hypoxia model group, positive control group and Saussurea involucrata alcohol extract group. Mice were put into low pressure oxygen chamber and decompressed, adapted to hypobaric hypoxia environment of simulated altitude of 8,000 m for 12 h, and then recovered to normal altitude. The mice were sacrificed and the liver mitochondria was isolated, the mitochondrial membrane potential and the activity of malate dehydrogenase, aconitase, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase and mitochondrial complex I, II and V were measured. RESULTS: Compared with hypoxia model group, Saussurea involucrata alcohol extract protected mitochondrial membrane potential, sustained the activities of aconitase, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and mitochondrial complex I, II and V under hypoxia condition. CONCLUSION: Saussurea involucrata alcohol extract can protect the liver mitochondrial function in mice under hypoxia condtion. PMID- 26672350 TI - [Effects of Suoquan Wan and Shenqi Wan on Urethra Function and beta-AR Function of Detrusor in Natural Aged Rats]. AB - OBJECTIVE: To investigate the effect of Suoquan Wan(SQW) and Jinkui Shenqi Wan(JKSQW) on urethra function and beta6-AR function of detrusor in natural aged rats. METHODS: young rats(3 months) and Aged rats(15 months) were chosen. Young rats were chosen as control, aged rats were randomly divided into three groups: model, JKSQW and SQW groups, 12 rats in each group. JKSQW and SQW were given the appropriate concentration once a day for six weeks. The effects of SQW and JKSQW on relaxation function of bladder detrusor was investigated, and their effects on bladder induced by beta3-AR agonist and beta3-AR agonist were further studied. Then, their effects on pressure of urethra were observed. RESULTS: Compared with the young group, detrusor compliance of natural aged model rats was increased, Emax and IA of agonist of beta3-AR including BRL37344 and ISO were decreased(P <0. 01), while PA2 of antagonist of beta3-AR were increased(P <0. 05). Compared with model group, SQW and JKSQW decreased the bladder compliance(P <0. 05), and increased Emax, IA and PD2 due to sensitivity of detrusor to agonist of beta3-AR and beta3-AR including BRL37344 and ISO(P <0. 05 or P < 0. 01) ,while decreased PA2 of antagonist of beta3-AR(P <0. 05). MUCP, MUP and FUL of aged rats were lower than those of normal rats. But SQW and JKSQW increased MUCP and MUP, and JKSQW increased FUL of aged rats(P <0. 05 or P <0. 01). CONCLUSION: SQW and JKSQW can remarkably adjust beta3-AR function on the detrusor and improve the closure ability of bladder detrusor of the natural aged rats. PMID- 26672351 TI - [Effects of Litchi chinensis Seed Saponins on Inhibiting Hyperplasia of Mammary Glands and Influence on Signaling Pathway of Estrogen in Rats]. AB - OBJECTIVE: To discuss the role of Litchi chinensis seed saponins on hyperplasia of mammary glands(HMG) and the influence of estrogen signaling pathways in rats. METHODS: In addition to eight non-pregnant female SD rats in normal control group, the other 32 pathologic models of HMG rat model were randomly divided into other four groups: model control group, low and high dose groups, which were given experimental drug of Litchi chinensis seed saponins (LSE) 0. 1 g/kg and 0. 2 g/kg, and the positive control group with experimental drug of tamoxifen 4 mg/kg. Then all model rats were orally administrated for four weeks. The diameter and height of nipple were measured, and the content changes of estradiol(E2) and progestrogen(P) in serum were detected with ELISA method. The HMG were detected by the morphology examination. The expression of estrogen receptor(ER) and progesterone receptor(PR) in the mammary glands were investigated by immunohistochemical staining. RESULTS: According to LSE in the low and high dose groups, it was discovered that the nipple diameter and height of HMG rats, the expression of ER and PR in HMG and the content of serum E2 were reduced, the content of serum P were improved, and the hyperplasia of mammary glands was inhibited. CONCLUSION: LSE can obviously inhibit the rat hyperplasia of mammary gland, and its possible mechanism is related to adjusting the transduction pathway of estrogen signal to lower estrogen levels. PMID- 26672352 TI - [Preparation and Dissolution Evaluation of Breviscapine Self-microemulsion]. AB - OBJECTIVE: To study the prescription and preparation technology of breviscapine self-microemulsion for oral administration, and to evaluate the quality, stability and in vitro dissolution. METHODS: The prescription and preparation technology were selected and optimized through the solubility experiment, compatibility test, and pseudo-ternary phase diagram method, using the self emulsifying time, appearance, particle diameter and stability as indexes. The droplet morphous, drug content, stability and dissolution were evaluated. Results:The prescription composition of breviscapine self-microemulsion was caprylic/capric triglyceride(GTCC,40%), Cremophor RH-40(50%), and PEG-400 (10%), with the drug loading of 7. 0 mg/g. The breviscapine self-microemulsion exhibited uniform and transparent,with the particle size of 38. 57 nm,Zeta potential of - 8. 80 mV. The results of dissolution indicated that the accumulative dissolution in 0. 1 mol/L hydrochloric acid was able to reach 90. 30% after 90 min, being 5. 9 times to that of the raw material medicine. The stability result showed that the content of breviscapine self-microemulsion was affected by high temperature, indicating it should be stored at low temperature. CONCLUSION: The preparation of breviscapine self-microemulsion is simple, which can increase the solubility of breviscapine in water and the absorption of breviscapine in the stomach and intestine, and conform to the main indexes of oral drug delivery system. It offers the basis for further research of breviscapine. PMID- 26672353 TI - [Extraction of 10-Deacetyl Baccatin by Supercritical CO2 from Taxus yunnanensis Branches and Leaves]. AB - OBJECTIVE: To study the supercritical CO2 fluids extraction (SFE) method to extract the components from Taxus yunnanensis. METHODS: Medicinal meterials were extracted by supercritical CO2, and then purified by industrial chromatography. Using the extraction yield of 10-DAB as the index,single factor test was carried out to investigate the effect of co-solvent, extraction time, extraction pressure, extraction temperature, pressure and temperature of separation kettle I. Then orthogonal experiment was used to optimize the best extraction condition. RESULTS: The suitable extraction condition was as follows: the ratio of co solvent (80% ethanol) amount and the madicinal materials was 3: 1, Separation kettle I pressure was 14 MPa, separation kettle I temperature was 40 degrees C, extraction pressure was 25 MPa, extraction temperature was 60 T and extraction time was 90 min. The extract was separated by industrial chromatographic and then crystallized. CONCLUSION: The supercritical CO2 extraction and purification process of 10-DAB were simple and feasible. PMID- 26672354 TI - [Purification Technology Optimization for Saponins from Ziziphi Spinosae Semen with Macroporous Adsorption Resin by Box-Behnken Design-Response Surface Methodology]. AB - OBJECTIVE: To compare the purification effect of saponins from Ziziphi Spinosae Semen with different types of macroporous adsorption resin, and to optimize its purification technology. METHODS: The type of macroporous resins was optimized by static adsorption method. The optimum technological conditions of saponins from Ziziphi Spinosae Semen was screened by single factor test and Box-Behnken Design Response Surface Methodology. RESULTS: AB-8 macroporous resin had better purification effect of total saponins than other resins, optimum technological parameters were as follows: column height-diameter ratio was 5: 1, the concentration of sample solution was 2. 52 mg/mL, resin adsorption quantity was 8. 915 mg/g, eluted by 3 BV water, flow rate of adsorption and elution was 2 BV/h, elution solvent was 75% ethanol, elution solvent volume was 5 BV. CONCLUSION: AB-8 macroporous resin has a good purification effect on jujuboside A. The optimized technology is stable and feasible. PMID- 26672355 TI - [The past 30 years of Chinese Journal of Biotechnology]. AB - This review addresses the association of "Chinese Journal of Biotechnology" and the development of biotechnology in China in the past 30 years. Topics include relevant awards and industrialization, development of the biotechnology discipline, and well know scientists in biotechnology, as well as perspectives on the journal. PMID- 26672356 TI - [Progress in industrial bioprocess engineering in China]. AB - The advances of industrial biotechnology highly depend on the development of industrial bioprocess researches. In China, we are facing several challenges because of a huge national industrial fermentation capacity. The industrial bioprocess development experienced several main stages. This work mainly reviews the development of the industrial bioprocess in China during the past 30 or 40 years: including the early stage kinetics model study derived from classical chemical engineering, researching method based on control theory, multiple parameter analysis techniques of on-line measuring instruments and techniques, and multi-scale analysis theory, and also solid state fermentation techniques and fermenters. In addition, the cutting edge of bioprocess engineering was also addressed. PMID- 26672358 TI - [The rise of enzyme engineering in China]. AB - Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China. PMID- 26672357 TI - [Glycotechnology in China]. AB - Glycotechnology is a new branch of biotechnology, emerged early 1990's. In this article, the international background of glycotechnology is briefly introduced and history of glycotechnology in China is reviewed. PMID- 26672359 TI - [Progress and prospect of biodiesel industry in China]. AB - The development of biodiesel and production feedstock in China was introduced, and the biodiesel production technologies as well as corresponding representative enterprises were reviewed. In addition, the development prospect of biodiesel industry in China was addressed. PMID- 26672360 TI - [Aminoglycoside gentamicin research: fundamental progress and new application prospects]. AB - As an important aminoglycosides antibiotic, gentamicin has been used clinically over decades. With the development in modern biological technology, the mechanisms of gentamicin action and resistance, its biosynthesis and structural modification were studied in great depth. Meanwhile, its emerging novel bioactivities and potential applications are also under extensive exploration. Here we summarize the latest progresses and prospects towards the future development of gentamicin for more efficient and effective uses. PMID- 26672361 TI - ["Nitrate stimulating effect" in Amycolatopsis mediterranei--from discovery to mechanistic studies]. AB - Nitrate not only remarkably stimulates the rifamycinbiosynthesis in Amycolatopsis mediterranei, but also influences the primary metabolisms, including the inhibition of fatty acids biosynthesis in the bacterial. This phenomenon has been designated as "Nitrate Stimulating Effect" by the late Prof. J.S. Chiaosince its discovery in the 1970's, and has been found in many other antibiotics-producing actinomycetes subsequently. Based on the research in his laboratory, we have revealed that the nitrate stimulation effect mainly manifests in two aspects over the last two decades. First, nitrate promotes the supply of rifamycin precursors, e.g., UDP-glucose, AHBA, malonyl-CoA and methylmalonyl-CoA. Specifically, the biosynthesis of fatty acids is inhibited by nitrate consequently the acetyl-CoA is shunted into malonyl-CoA. Second, nitrate facilitates the expression of genes in the rifclulsterthat encodes rifamycin biosynthetic enzymes. Following our current understanding, the future research will focus on the signals, the signal transduction pathway and the molecular mechanisms that dictate nitrate-mediated transcriptional and post-translational regulations. PMID- 26672362 TI - [Progress in monoclonal antibody-based immunotherapy for cancer treatment]. AB - More than 100 years ago, Paul Ehrlich first proposed the "magic bullets" concept in which antibody targeting disease related antigen can fight against human disease. Since then, with the development of hybridoma technology for monoclonal antibody production and cancer serum therapy, immunotherapy based monoclonal antibody bas been used in chinical practice to treat hematological and solid tumor. Up to now, more than 20 recombinant antibody drugs were approved for cancer treatment worldwide. In recent years, the next-generation antibody drug, including immune checkpoint antagonists, bi-specific antibody, and antibody drug conjugates have successfully cured various malignant tumor. This review recalled the history of monoclonal antibody as potent immunotherapy of cancer firstly, and focused on the next-generation antibody drug's mechanism of action, construction strategies, and the side effects in clinic. Lastly, the future trend of anti tumor antibody drug was also discussed. PMID- 26672363 TI - [Progress in stem cells and regenerative medicine]. AB - Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools. PMID- 26672364 TI - [Porcine circovirus type 2 and PCV2-systemic disease--a review]. AB - Porcine circovirus type 2 (PCV2) can cause immunosuppression on herds. PCV2, as an essential pathogen of PCV2-systemic disease (PCV2-SD), has caused considerable economic losses in pig industry worldwide. Here we review and address the evolution, viral protein and immunolesion of PCV2 and preventive techniques of PCV2-SD. PMID- 26672365 TI - [Review of transgenic crop breeding in China]. AB - The development history and fundamental experience of transgenic crops (Genetically modified crops) breeding in China for near 30 years were reviewed. It was illustrated that a scientific research, development and industrialization system of transgenic crops including gene discovery, transformation, variety breeding, commercialization, application and biosafety assessment has been initially established which was few in number in the world. The research innovative capacity of transgenic cotton, rice and corn has been lifted. The research features as well as relative advantages have been initially formed. The problems and challenges of transgenic crop development were discussed. In addition, three suggestions of promoting commercialization, speeding up implementation of the Major National Project of GM Crops, and enhancing science communication were made. PMID- 26672366 TI - [Development of bioremediation in China--a review]. AB - The development of bioremediation for contaminated soil in China during past 30 years was briefly reviewed, mainly including the developing stages, bioremediation techniques/strategies and their applications, and isolation, screening and characterizations of microbial strains for bioremediation as well as their efficiencies in bioremediation of contaminated soils. Finally, future development of bioremediation techniques/strategies and their applications were also discussed. PMID- 26672367 TI - [Progress of new-generation genome editing mediated by engineered endonucleases]. AB - Genome editing refers to the experimental methods to targeted modify specific loci in the genomic DNA sequence. In recent years, engineered endonucleases, including ZFN, TALEN and CRISPR/Cas, have been developed as a new-generation genome editing technique, and greatly improved the feasibility of gene function analyses, gene therapy, etc. Here, we briefly summarize the basic principle, developmental process and applications of this technology. PMID- 26672368 TI - [Recent development of Pichia pastoris system: current status and future perspective]. AB - With more than 20 years of development, Pichia pastoris system has been extensively used both on a lab and industrial scale. This review outlines the progress made on P. pastoris from aspects of protein expression, molecular engineering tools and methods, and biochemical production. This review also provides perspectives on the current challenges and future directions of this important system. PMID- 26672369 TI - [Biosynthesis-based production improvement and structure modification of erythromycin A]. AB - Erythromycin A is a clinically important macrolide antibiotic with broad-spectrum activity. Its biosynthesis involves the formation of the 14-membered skeleton catalyzed by polyketide synthases, and the modification steps such as hydroxylation, glycosylation and methylation. Based on the understanding of the biosynthetic mechanism, it is reliable to genetically manipulate the erythromycin A-producing strain for production improvement and structure modification. In this paper, we reviewed the progress regarding erythromycin A in high-producing strain construction and chemical structure derivation, to provide insights for further development. PMID- 26672371 TI - [Biologic treatments for hereditary diseases]. AB - Hereditary disease, especially monogenic disease is one of the major causes for malformation and disability of children. Most hereditary diseases have no effective therapy besides clinical symptomatic treatment. Biological techniques targeting casual genes or related signaling genes, such as transgenic, RNA interfere, genome editing, have been successfully applied in treating some hereditary diseases. However, most biological, treatments were carried out in animals, further confirmation of the effectiveness and safety of these therapies, and development of more therapeutic approaches based on mechanisms are needed before clinical trials. PMID- 26672370 TI - [Research and industrialization of biobased materials in China]. AB - This paper reviews the research and commercialization progresses of biobased polymeric materials including polyhydroxyalkanoates (PHA), polylactides (PLA), poly (butylene succinate) (PBS) and its monomer succinate, and CO2 copolymer poly (propylene carbonate), especially these efforts made in China. PMID- 26672372 TI - [Advances in genetic engineering of plant virus resistance]. AB - Plant virus is one of the most economical devastating microorganisms for global agriculture. Although several strategies are useful for controlling viral infection, such as resistant breeds cultivation, chemical bactericides treatment, blocking the infection source, tissue detoxification and field sanitation, viral disease is still a problem in agricultural production. Genetic engineering approach offers various options for introducing virus resistance into crop plants. This paper reviews the current strategies of developing virus resistant transgenic plants. PMID- 26672373 TI - [Progress in synthetic biology of "973 Funding Program" in China]. AB - This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems. PMID- 26672374 TI - Response to Comment on "A Comprehensive Analysis of Groundwater Quality in The Barnett Shale Region". PMID- 26672383 TI - The role of octopamine receptor agonists in the synergistic toxicity of certain insect growth regulators (IGRs) in controlling Dengue vector Aedes aegypti (Diptera: Culicidae) mosquito. AB - The synergistic action of octopamine receptor agonists (OR agonists) on many insecticide classes (e.g., organophosphorus, pyrethroids, and neonicotinoids) on Aedes aegypti L. has been reported recently. An investigation of OR agonist's effect on insect growth regulators (IGRs) was undertaken to provide a better understanding of the mechanism of action. Based on the IGR bioassay, pyriproxyfen was the most potent IGR insecticide tested (EC50=0.0019ng/ml). However, the lethal toxicity results indicate that diafenthiuron was the most potent insecticide (LC50=56ng/cm(2)) on A. aegypti adults after 24h of exposure. The same trend was true after 48 and 72h of exposure. Further, the synergistic effects of OR agonists plus amitraz (AMZ) or chlordimeform (CDM) was significant on adults. Among the tested synergists, AMZ increased the potency of the selected IGRs on adults the greatest. As results, OR agonists were largely synergistic with the selected IGRs. OR agonists enhanced the lethal toxicity of IGRs, which is a valuable new tool in the field of A. aegypti control. However, further field experiments need to be done to understand the unique potential role of OR agonists and their synergistic action on IGRs. PMID- 26672384 TI - Impact of organic polyelectrolytes on coagulation of source-separated black water. AB - Household wastewater is originated from common people's activities and has a potential harmful impact on the environment if discharged directly without proper treatment. Toilet wastewater or black water (BW) contains urine, faeces, toilet paper and flushing water and it contains the majority of pollutants obtained from a single household. In this study, the focus was on BW treatment using chemical methods. The main goal of current research was to define the possibility and applicability of conventional coagulants and flocculants in direct chemical treatment of vacuum-collected BW to remove particles, organic matter and phosphorous. After the definition of dosing ranges, based on the equivalent doses in conventional municipal and industrial wastewater treatment data, aluminium and iron coagulants, organic polyelectrolytes (polymers with anionic, neutral and cationic charge with different molecular weights) and their various combinations were tested using the well-known jar-test laboratory method to study aggregation and solid-liquid separation processes in raw BW. The most important process parameter during the coagulation was pH level, dependent on the type and doses of metal salts. Some side processes were found to occur while using iron-based coagulants. Dosing of either single coagulants or single polymers did not give satisfactory results, while a combination of aluminium salts and cationic polymers showed high removal rates in total suspended solids, total chemical oxygen demand and ortho-phosphates, reaching 97.8%, 92% and 98.6%, respectively, with the optimal doses of chemicals. Cationic polymers with the lowest molecular weight and highest charge density were the most efficient in combination with aluminium coagulants. PMID- 26672385 TI - Effects of uncoated and citric acid coated cerium oxide nanoparticles, bulk cerium oxide, cerium acetate, and citric acid on tomato plants. AB - Little is known about the physiological and biochemical responses of plants exposed to surface modified nanomaterials. In this study, tomato (Solanum lycopersicum L.) plants were cultivated for 210days in potting soil amended with uncoated and citric acid coated cerium oxide nanoparticles (nCeO2, CA+nCeO2) bulk cerium oxide (bCeO2), and cerium acetate (CeAc). Millipore water (MPW), and citric acid (CA) were used as controls. Physiological and biochemical parameters were measured. At 500mg/kg, both the uncoated and CA+nCeO2 increased shoot length by ~9 and ~13%, respectively, while bCeO2 and CeAc decreased shoot length by ~48 and ~26%, respectively, compared with MPW (p<=0.05). Total chlorophyll, chlo-a, and chlo-b were significantly increased by CA+nCeO2 at 250mg/kg, but reduced by bCeO2 at 62.5mg/kg, compared with MPW. At 250 and 500mg/kg, nCeO2 increased Ce in roots by 10 and 7 times, compared to CA+nCeO2, but none of the treatments affected the Ce concentration in above ground tissues. Neither nCeO2 nor CA+nCeO2 affected the homeostasis of nutrient elements in roots, stems, and leaves or catalase and ascorbate peroxidase in leaves. CeAc at 62.5 and 125mg/kg increased B (81%) and Fe (174%) in roots, while at 250 and 500mg/kg, increased Ca in stems (84% and 86%, respectively). On the other hand, bCeO2 at 62.5 increased Zn (152%) but reduced P (80%) in stems. Only nCeO2 at 62.5mg/kg produced higher total number of tomatoes, compared with control and the rest of the treatments. The surface coating reduced Ce uptake by roots but did not affect its translocation to the aboveground organs. In addition, there was no clear effect of surface coating on fruit production. To our knowledge, this is the first study comparing the effects of coated and uncoated nCeO2 on tomato plants. PMID- 26672386 TI - Perspectives for integrating human and environmental exposure assessments. AB - Integrated Risk Assessment (IRA) has been defined by the EU FP7 HEROIC Coordination action as "the mutual exploitation of Environmental Risk Assessment for Human Health Risk Assessment and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process" (Wilks et al., 2015). Since exposure assessment and hazard characterization are the pillars of risk assessment, integrating Environmental Exposure assessment (EEA) and Human Exposure assessment (HEA) is a major component of an IRA framework. EEA and HEA typically pursue different targets, protection goals and timeframe. However, human and wildlife species also share the same environment and they similarly inhale air and ingest water and food through often similar overlapping pathways of exposure. Fate models used in EEA and HEA to predict the chemicals distribution among physical and biological media are essentially based on common properties of chemicals, and internal concentration estimations are largely based on inter-species (i.e. biota to-human) extrapolations. Also, both EEA and HEA are challenged by increasing scientific complexity and resources constraints. Altogether, these points create the need for a better exploitation of all currently existing data, experimental approaches and modeling tools and it is assumed that a more integrated approach of both EEA and HEA may be part of the solution. Based on the outcome of an Expert Workshop on Extrapolations in Integrated Exposure Assessment organized by the HEROIC project in January 2014, this paper identifies perspectives and recommendations to better harmonize and extrapolate exposure assessment data, models and methods between Human Health and Environmental Risk Assessments to support the further development and promotion of the concept of IRA. Ultimately, these recommendations may feed into guidance showing when and how to apply IRA in the regulatory decision-making process for chemicals. PMID- 26672387 TI - Modeling packed bed sorbent systems with the Pore Surface Diffusion Model: Evidence of facilitated surface diffusion of arsenate in nano-metal (hydr)oxide hybrid ion exchange media. AB - This study explores the possibility of employing the Pore Surface Diffusion Model (PSDM) to predict the arsenic breakthrough curve of a packed bed system operated under continuous flow conditions with realistic groundwater, and consequently minimize the need to conduct pilot scale tests. To provide the nano-metal (hydr)oxide hybrid ion exchange media's performance in realistic water matrices without engaging in taxing pilot scale testing, the multi-point equilibrium batch sorption tests under pseudo-equilibrium conditions were performed; arsenate breakthrough curve of short bed column (SBC) was predicted by the PSDM in the continuous flow experiments; SBC tests were conducted under the same conditions to validate the model. The overlapping Freundlich isotherms suggested that the water matrix and competing ions did not have any denoting effect on sorption capacity of the media when the matrix was changed from arsenic-only model water to real groundwater. As expected, the PSDM provided a relatively good prediction of the breakthrough profile for arsenic-only model water limited by intraparticle mass transports. In contrast, the groundwater breakthrough curve demonstrated significantly faster intraparticle mass transport suggesting to a surface diffusion process, which occurs in parallel to the pore diffusion. A simple selection of DS=1/2 DP appears to be sufficient when describing the facilitated surface diffusion of arsenate inside metal (hydr)oxide nano-enabled hybrid ion exchange media in presence of sulfate, however, quantification of the factors determining the surface diffusion coefficient's magnitude under different treatment scenarios remained unexplored. PMID- 26672388 TI - New Monomeric Stilbenoids from Peanut (Arachis hypogaea) Seeds Challenged by an Aspergillus flavus Strain. AB - Two new stilbene derivatives have been isolated from peanut seeds challenged by an Aspergillus flavus strain, along with chiricanine B, which has not been previously reported from peanuts, as well as a stilbenoid reported previously only as a synthetic product. The structures of these new putative phytoalexins were determined by analysis of (1)H and (13)C NMR, HRESIMS, MS(n), and UV data. The new stilbenoids were named arahypin-13 (21), arahypin-14 (22), and arahypin 15 (23). Together with other known bioactive peanut stilbenoids that were also produced in the challenged seeds, these new compounds may play a defensive role against invasive fungi. PMID- 26672389 TI - Critical Assessment of TD-DFT for Excited States of Open-Shell Systems: I. Doublet-Doublet Transitions. AB - A benchmark set of 11 small radicals is set up to assess the performance of time dependent density functional theory (TD-DFT) for the excited states of open-shell systems. Both the unrestricted (U-TD-DFT) and spin-adapted (X-TD-DFT) formulations of TD-DFT are considered. For comparison, the well-established EOM CCSD (equation-of-motion coupled-cluster with singles and doubles) is also used. In total, 111 low-lying singly excited doublet states are accessed by all the three approaches. Taking the MRCISD+Q (multireference configuration interaction with singles and doubles plus the Davidson correction) results as the benchmark, it is found that both U-TD-DFT and EOM-CCSD perform well for those states dominated by singlet-coupled single excitations (SCSE) from closed-shell to open shell, open-shell to vacant-shell, or closed-shell to vacant-shell orbitals. However, for those states dominated by triplet-coupled single excitations (TCSE) from closed-shell to vacant-shell orbitals, both U-TD-DFT and EOM-CCSD fail miserably due to severe spin contaminations. In contrast, X-TD-DFT provides balanced descriptions of both SCSE and TCSE. As far as the functional dependence is concerned, it is found that, when the Hartree-Fock ground state does not suffer from the instability problem, both global hybrid (GH) and range-separated hybrid (RSH) functionals perform grossly better than pure density functionals, especially for Rydberg and charge-transfer excitations. However, if the Hartree Fock ground state is instable or nearly instable, GH and RSH tend to underestimate severely the excitation energies. The SAOP (statistically averaging of model orbital potentials) performs more uniformly than any other density functionals, although it generally overestimates the excitation energies of valence excitations. Not surprisingly, both EOM-CCSD and adiabatic TD-DFT are incapable of describing excited states with substantial double excitation characters. PMID- 26672390 TI - Rooting Out Gun Violence. PMID- 26672391 TI - Management of opioid use disorders among veterans in subacute rehab: Use of an interdisciplinary task force to address an emerging concern. AB - There is both rapidly growing need, and limited evidence-based guidelines, for the management of opioid use disorders in subacute rehab and other nonaddiction medical settings. Following 2 unintentional opioid overdoses within the Community Living Center (CLC), a VA (Veterans Administration) subacute rehab setting, an interdisciplinary CLC Addictions Task Force was created to address a critical issue: how to best meet the combined neuropsychiatric and medical needs of the opiate use disorder patient through a multifaceted treatment approach. The goals of the task force were to develop and institute educational initiatives for providers; create patient care guidelines; increase safety on the unit; improve provider confidence when caring for this high-risk population; and mitigate the risk of unintentional overdose. The task force divided into 4 working groups to meet these aims. Process and outcomes are discussed. We found that in-services by addiction specialists improved clinician comfort in caring for this high-risk patient group. Specific areas that yielded the greatest clinician satisfaction ratings included didactics on how to identify at-risk patients and techniques on how to manage the patient in a general rehab setting. Utilizing an interdisciplinary approach, and an iterative process, at all stages was critical to the success of the CLC Addictions Task Force, as it improved buy-in and motivation from all disciplines. Improvements have been made to enhance patient safety, improve communication amongst providers, and provide a foundation to improve patient outcomes. Our preliminary work to enhance the identification and management of opioid use disorders at our CLC is an important first step towards a standardized curriculum that could be applied to other VA and non-VA subacute rehab settings. PMID- 26672392 TI - Simultaneous cochlear implantation and labyrinthectomy for advanced Meniere's disease. AB - BACKGROUND: Patients with Meniere's disease can develop unaidable sensorineural hearing loss. Cochlear implantation has recently been utilised in this group with favourable results. A more challenging group are those with intractable vertigo, and they have traditionally posed a significant management dilemma. CASE REPORT: Two female patients with unaidable hearing and recurrent incapacitating vertigo attacks despite conservative management underwent simultaneous labyrinthectomy and cochlear implantation. There was complete resolution of vertigo in both patients. Speech perception in quiet conditions and the ability to hear in background noise improved considerably. CONCLUSION: Surgical labyrinthectomy is effective for the elimination of vertigo in Meniere's disease patients. The major disadvantage in the past was loss of residual hearing. Cochlear implantation is now an option in these patients. The benefits of simultaneous labyrinthectomy with cochlear implantation include the prevention of implantation of a fibrosed or ossified cochlea, a decrease in the duration of deafness, and a single operative procedure. PMID- 26672393 TI - Error Argumentation Enhance Adaptability in Adults With Low Motor Ability. AB - The authors focused on young adults with varying degrees of motor difficulties and examined their adaptability in a visuomotor adaptation task where the visual feedback of participants' movement error was presented with either 1:1 ratio (i.e., regular feedback schedule) or 1:2 ratio (i.e., enhanced feedback schedule). Within-subject design was used with two feedback schedules counter balanced and separated for 10 days. Results revealed that participants with greater motor difficulties showed less adaptability than those with normal motor abilities in the regular feedback schedule; however, all participants demonstrated similar level of adaptability in the enhanced feedback schedule. The results suggest that error argumentation enhances adaptability in adults with low motor ability. PMID- 26672394 TI - An Alkyloxyphenyl Group as a Sterically Hindered Substituent on a Triphenylamine Donor Dye for Effective Recombination Inhibition in Dye-Sensitized Solar Cells. AB - Recombination reactions in dye-sensitized solar cells (DSSCs) may substantially decrease the open-circuit voltage (Voc) with cobalt complex redox electrolyte. Managing steric hindrance in the dye structure is necessary to inhibit recombination reactions and thereby increase the Voc and achieve high power conversion efficiency (PCE). New dyes with large-sized donors based on triphenylamine and modified with 4-(hexyloxy)phenyl groups were developed to identify an effective inhibitor for the recombination reaction in DSSCs with a cobalt complex redox electrolyte. The 4-(hexyloxy)phenyl tetra-adducts dye MK-123 effectively inhibited the recombination reaction, and the DSSC fabricated using this dye exhibited the highest Voc (greater than 900 mV) among the cells with the investigated dyes. However, the short-circuit current (Jsc) of the MK-123 cell was lower than that of the cell with the simple triphenylamine donor dye, MK-89. In contrast, the cell with bis-adducts dye MK-136 also exhibited an increase in its Voc without a decrease in its Jsc. Among the investigated dyes, MK-136 exhibited the highest PCE of 8.9%. The effects of the steric hindrance of the 4 (hexyloxy)phenyl substituent are discussed. PMID- 26672395 TI - Triazoloazine-Diazomethylazine Valence Isomerization. [1,2,3]Triazolo[1,5 a]pyridines and 2-Diazomethylpyridines. AB - 2-Diazomethylpyridines 1D and 6D, the valence isomers of [1,2,3]triazolo[1,5 a]pyridines 1T and 6T, have been observed directly at ~2080 cm(-1) by a combination of mild flash vacuum pyrolysis (FVP) at 200-600 degrees C with low temperature IR spectroscopy. Calculations confirm a ca. 17 kcal/mol barrier for the formation of 2-diazomethylpyridine 1D from [1,2,3]triazolo[1,5-a]pyridine 1T, the diazo compound lying ca. 5 kcal/mol above the triazole. In the higher temperature range (400-600 degrees C) 2-diazomethylpyridine 1D eliminates N2 with formation of 2-pyridylcarbene 2 and rearrangement to 1-cyanocyclopentadiene 4. 2-Diazomethylpyridine 1D undergoes 1,3-dipolar cycloaddition with tetracyanoethylene (TCNE) at 20-90 degrees C to yield 3-(2 pyridyl)cyclopropanetetracarbonitrile 11 and 3-(tricyanovinyl) [1,2,3]triazolo[1,5-a]pyridine 13T via unobserved pyrazolines 10 and 12. FVP of triazole 13T affords an IR absorption at 2080 cm(-1) ascribed to the corresponding diazo compound 13D. PMID- 26672396 TI - Antimicrobial Cellobiose Dehydrogenase-Chitosan Particles. AB - Increasing prevalence of chronic wounds and microbial infection constitute a severe health challenge. The situation is further complicated by emerging multidrug resistance making the treatment of infections increasingly difficult. Here, a novel antimicrobial system based on in situ release of hydrogen peroxide (H2O2) by cellobiose dehydrogenase (CDH) immobilized on chitosan (CTS) particles is described. Covalent immobilization using carbodiimide coupling lead to a higher amount of protein immobilized on CTS (104 MUg CDH/mg CTS) when compared to noncovalent immobilization, which, however, showed highest recovery of CDH activity (0.01 U/mg CTS). The CDH-CTS in situ generated H2O2 completely inhibited growth of Escherichia coli and Staphylococcus aureus over a period of 24 h. This resilient antimicrobial system represents a novel strategy for preventing infection with potential application in counteracting microbial colonization of chronic wounds. PMID- 26672397 TI - Draft genome sequence of Thermococcus sp. EP1, a novel hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent on the East Pacific Rise. AB - Thermococcus sp. strain EP1 is a novel anaerobic hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent on the East Pacific Rise. It grows optimally at 80 degrees C and can produce industrial enzymes at high temperature. We report here the draft genome of EP1, which contains 1,819,157 bp with a G+C content of 39.3%. The sequence will provide the genetic basis for better understanding of adaptation to hydrothermal environment and the development of novel thermostable enzymes for industrial application. PMID- 26672399 TI - Totally anomalous pulmonary venous drainage - supracardiac type: ultrasound assessment of anatomically determined stenosis of the vertical vein collecting pulmonary venous return and Ultrasound diagnosis of pulmonary sling with proximal stenosis of left pulmonary artery and patent arterial duct. PMID- 26672398 TI - Antioxidant defence systems in the protozoan pathogen Giardia intestinalis. AB - The microaerophilic protist Giardia intestinalis is the causative agent of giardiasis, one of the most common intestinal infectious diseases worldwide. The pathogen lacks not only respiratory terminal oxidases (being amitochondriate), but also several conventional antioxidant enzymes, including catalase, superoxide dismutase and glutathione peroxidase. In spite of this, since living attached to the mucosa of the proximal small intestine, the parasite should rely on an efficient antioxidant system to survive the oxidative and nitrosative stress conditions found in this tract of the human gut. Here, we review current knowledge on the antioxidant defence systems in G. intestinalis, focusing on the progress made over the last decade in the field. The relevance of this research and future perspectives are discussed. PMID- 26672400 TI - Companies should test the limits of their decontamination procedures--Reply to: Comments on "Ethnic hair care products may increase false positive in hair" V. Hill et al. PMID- 26672402 TI - The Relationship of Health Literacy With Use of Digital Technology for Health Information: Implications for Public Health Practice. AB - OBJECTIVE: An understanding of the association of health literacy with patterns related to access and usage of digital technologies and preferences for sources of health information is necessary for public health agencies and organizations to appropriately target channels for health information dissemination. DESIGN: A cross-sectional telephone survey was conducted in New York State. Health literacy was assessed using the Morris Single-Item Screener, a self-report question. A weighted analysis was conducted utilizing Stata/SE. PARTICIPANTS: The final sample size of New York State residents used for analysis was 1350. RESULTS: In general, self-report health literacy did not predict digital technology use (ie, Internet and smartphone use, text messaging) but was associated with certain digital activities. People with low self-report health literacy were less likely to use search engines (P = .026) but more likely to get health information from social networking sites (P = .002) and use health-related phone apps (P = .046). With respect to health information seeking, those with lower self-report health literacy reported greater difficulty with their most recent search for health information. Furthermore, they were more likely to prefer text messages (P = .013) and radio (P = .022), 2 text-limited communication channels, to receive health information than those with higher self-report health literacy. CONCLUSIONS: While self-report health literacy does not appear to influence access to and use of digital technologies, there is a strong association with experiences searching for health information and preferences for health information sources. Public health agencies and organizations should consider the needs and preferences of people with low health literacy when determining channels for health information dissemination. They should also consider implementing interventions to develop health information-seeking skills in populations they serve and prepare information and materials that are easily accessible and understandable. PMID- 26672401 TI - Making Homes Healthy: International Code Council Processes and Patterns. AB - CONTEXT: Americans spend more than 90% of their time indoors, so it is important that homes are healthy environments. Yet many homes contribute to preventable illnesses via poor air quality, pests, safety hazards, and others. Efforts have been made to promote healthy housing through code changes, but results have been mixed. In support of such efforts, we analyzed International Code Council's (ICC) building code change process to uncover patterns of content and context that may contribute to successful adoptions of model codes. OBJECTIVE: Discover patterns of facilitators and barriers to code amendments proposals. DESIGN: Mixed methods study of ICC records of past code change proposals. N = 2660. SETTING: N/A. PARTICIPANTS: N/A. MAIN OUTCOME MEASURE(S): There were 4 possible outcomes for each code proposal studied: accepted as submitted, accepted as modified, accepted as modified by public comment, and denied. RESULTS: We found numerous correlates for final adoption of model codes proposed to the ICC. The number of proponents listed on a proposal was inversely correlated with success. Organizations that submitted more than 15 proposals had a higher chance of success than those that submitted fewer than 15. Proposals submitted by federal agencies correlated with a higher chance of success. Public comments in favor of a proposal correlated with an increased chance of success, while negative public comment had an even stronger negative correlation. CONCLUSIONS: To increase the chance of success, public health officials should submit their code changes through internal ICC committees or a federal agency, limit the number of cosponsors of the proposal, work with (or become) an active proposal submitter, and encourage public comment in favor of passage through their broader coalition. PMID- 26672403 TI - Active Communities, Active Economies. PMID- 26672404 TI - Quality of HIV Testing Data Before and After the Implementation of a National Data Quality Assessment and Feedback System. AB - CONTEXT: In 2010, the Centers for Disease Control and Prevention (CDC) implemented a national data quality assessment and feedback system for CDC-funded HIV testing program data. OBJECTIVE: Our objective was to analyze data quality before and after feedback. DESIGN: Coinciding with required quarterly data submissions to CDC, each health department received data quality feedback reports and a call with CDC to discuss the reports. Data from 2008 to 2011 were analyzed. SETTING: Fifty-nine state and local health departments that were funded for comprehensive HIV prevention services. PARTICIPANTS: Data collected by a service provider in conjunction with a client receiving HIV testing. INTERVENTION: National data quality assessment and feedback system. MAIN OUTCOME MEASURES: Before and after intervention implementation, quality was assessed through the number of new test records reported and the percentage of data values that were neither missing nor invalid. Generalized estimating equations were used to assess the effect of feedback in improving the completeness of variables. RESULTS: Data were included from 44 health departments. The average number of new records per submission period increased from 197 907 before feedback implementation to 497 753 afterward. Completeness was high before and after feedback for race/ethnicity (99.3% vs 99.3%), current test results (99.1% vs 99.7%), prior testing and results (97.4% vs 97.7%), and receipt of results (91.4% vs 91.2%). Completeness improved for HIV risk (83.6% vs 89.5%), linkage to HIV care (56.0% vs 64.0%), referral to HIV partner services (58.9% vs 62.8%), and referral to HIV prevention services (55.3% vs 63.9%). Calls as part of feedback were associated with improved completeness for HIV risk (adjusted odds ratio [AOR] = 2.28; 95% confidence interval [CI], 1.75-2.96), linkage to HIV care (AOR = 1.60; 95% CI, 1.31-1.96), referral to HIV partner services (AOR = 1.73; 95% CI, 1.43-2.09), and referral to HIV prevention services (AOR = 1.74; 95% CI, 1.43-2.10). CONCLUSIONS: Feedback contributed to increased data quality. CDC and health departments should continue monitoring the data and implement measures to improve variables of low completeness. PMID- 26672405 TI - Using Evidence-Based Interventions to Improve Cancer Screening in the National Breast and Cervical Cancer Early Detection Program. AB - CONTEXT: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening to low-income, un-, and underinsured women through more than 11 000 primary care clinics. The program is well-positioned to work with health systems to implement evidence-based interventions (EBIs) to increase screening among all women. OBJECTIVE: To collect baseline data on EBI use, evaluation of EBIs, and related training needs among NBCCEDP grantees. DESIGN: The Centers for Disease Control and Prevention conducted a Web-based survey in late 2013 among NBCCEDP grantees for the period July 2012 to June 2013. This was the first systematic assessment of EBIs among NBCCEDP grantees. SETTING: The Centers for Disease Control and Prevention's NBCCEDP. PARTICIPANTS: Primarily program directors/coordinators for all 67 NBCCEDP grantees. MAIN OUTCOME MEASURES: Data captured were used to assess implementation of 5 EBIs, their evaluation, and related training needs. Frequencies and proportions were determined. Cluster analysis identified grantees with similar patterns of EBI use for NBCCEDP clients and providers. RESULTS: On average, 4.1 of 5 EBIs were implemented per grantee for NBCCEDP clients and providers. Four clusters were identified including "high overall EBI users," "high provider EBI users," "high EBI users with no provider assessment and feedback," and "high client EBI users." Only 1.8 EBIs were implemented, on average, with non-NBCCEDP clients and providers. Fewer than half (n = 32, 47.8%) of grantees conducted process or outcome evaluation of 1 or more EBIs. Overall, 47.6% of grantees reported high or medium training needs for client-oriented EBIs and 54.3% for provider-oriented EBIs. CONCLUSIONS: The NBCCEDP grantees are implementing EBIs extensively with clients and providers. Increased EBI use among non-NBCCEDP clients/providers is needed to extend the NBCCEDP's reach and impact. Grantee training and technical assistance is necessary across EBIs. In addition, grantees' use of process and outcome evaluation of EBI implementation must be increased to inform effective program implementation. PMID- 26672406 TI - Early Childhood Education to Promote Health Equity: A Community Guide Systematic Review. AB - CONTEXT: Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center based early childhood education. DESIGN: A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review. RESULTS: There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting. CONCLUSIONS: Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity. PMID- 26672407 TI - US State-Level Policy Responses to the Ebola Outbreak, 2014-2015. AB - CONTEXT: The 2014-2015 Ebola epidemic in West Africa raised concerns about the potential occurrence of an Ebola outbreak in the United States. The federal government and individual states developed guidance and policies to determine how to manage individuals within the United States who may have been exposed to Ebola. DESIGN: A total of 139 documents describing state policies for individuals considered at risk for Ebola and the requirements, as well as restrictions these individuals may be subject to, were systematically identified and analyzed. RESULTS: A wide range of policy responses and variations on quarantine, movement restrictions, exposure categories, and monitoring were found. While the majority of states reflected US Centers for Disease Control and Prevention guidance, some states enacted aggressive quarantine policies and movement restrictions, developed unique categorization strategies, and established more frequent monitoring procedures. CONCLUSIONS: Findings may help public health practitioners and policymakers anticipate what policies could be implemented in response to future infectious disease threats. Furthermore, practitioners and policymakers should assume that some variation in response policies will occur at the state level. PMID- 26672408 TI - Recommendation for Center-Based Early Childhood Education to Promote Health Equity. AB - The Community Preventive Services Task Force recommends early childhood education programs based on strong evidence of effectiveness in improving educational outcomes associated with long-term health and sufficient evidence of effectiveness in improving social- and health-related outcomes. When provided to low-income or racial and ethnic minority communities, early childhood education programs are likely to reduce educational achievement gaps, improve the health of low-income student populations, and promote health equity. PMID- 26672409 TI - Intercalation Pseudocapacitance in Ultrathin VOPO4 Nanosheets: Toward High-Rate Alkali-Ion-Based Electrochemical Energy Storage. AB - There is a growing need for energy storage devices in numerous applications where a large amount of energy needs to be either stored or delivered quickly. The present paper details the study of alkali-ion intercalation pseudocapacitance in ultrathin VOPO4 nanosheets, which hold promise in high-rate alkali-ion based electrochemical energy storage. Starting from bulk VOPO4.2H2O chunks, VOPO4 nanosheets were obtained through simple ultrasonication in 2-propanol. These nanosheets as the cathode exhibit a specific capacity of 154 and 136 mAh/g (close to theoretical value 166 mAh/g) for lithium and sodium storage devices at 0.1 C and 100 and ~70 mAh/g at 5 C, demonstrating their high rate capability. Moreover, the capacity retention is maintained at 90% for lithium ion storage and 73% for sodium ion storage after 500 cycles, showing their reasonable stability. The demonstrated alkali-ion intercalation pseudocapacitance represents a promising direction for developing battery materials with promising high rate capability. PMID- 26672410 TI - Prediction of Angiographic Extent of Coronary Artery Disease on the Basis of Clinical Risk Scores in Patients of Unstable Angina. AB - BACKGROUND: The correlation of clinical risk predictors and clinical risk scores: Thrombolysis in Myocardial Infarction (TIMI), Platelet Glycoprotein IIb-IIIa in Unstable Angina, Receptor Suppression Using Integrilin Therapy (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores in Unstable Angina with angiographic extent of Coronary Artery Disease (CAD) is not known. AIM: To know the correlation of clinical risk scores with angiographic extent of coronary artery disease. MATERIALS AND METHODS: This was a hospital based single centre, cross-sectional, observational, descriptive study conducted at a tertiary care teaching institute. One hundred and sixty patients with acute unstable angina were evaluated for presence of 9 clinical predictors and their 3 risk scores were calculated. All patients underwent coronary angiography. Correlation with Modified Gensini score and percentage stenosis in culprit artery was done. STATISTICAL ANALYSIS: Data were summarized in the form of Mean, Standard Deviation and Proportions. Multiple linear regressions, Student's t-test and Pearson's coefficient 'r' were also used. RESULTS: Use of aspirin, age >= 65 years & presence of Congestive Heart Failure (CHF) were stronger predictors of Modified Gensini score. Presence of elevated enzymes and age >65 years were more significant predictors of percentage stenosis of culprit artery. GRACE score had better correlation with Modified Gensini score, PURSUIT score had more correlation with percentage stenosis in culprit artery. CONCLUSION: Use of Aspirin, age >= 65 years, presence of CHF and presence of elevated enzymes are stronger predictors of extent of CAD. Hence we recommend that these factors be given more importance. GRACE and PURSUIT risk scores had more correlation with angiographic extent of CAD. PMID- 26672411 TI - Smokeless tobacco research. PMID- 26672412 TI - The comparative evaluation of fracture resistance and microleakage in bonded amalgam, amalgam, and composite resins in primary molars. AB - BACKGROUND: The intense development of adhesive restorative materials and parents' preferences for esthetic restorations prompt clinicians to use alternative restorative materials for primary molars. Amalgam, however, is the choice of material when it comes to occlusal stress bearing areas, either in primary or permanent molars. To overcome the drawbacks of amalgam and restorative adhesive materials, the bonded amalgam technique is employed. AIMS: To evaluate microleakage and fracture resistance of bonded amalgam in primary molars, and compare it with the microleakage and fracture resistance of high-copper amalgam and composite resin materials. SETTINGS AND DESIGN: An in vitro study and 60 caries-free primary molars were used. SUBJECTS AND METHODS: A total of 60 samples were randomly divided into two equal groups for the evaluation of microleakage and fracture resistance. Class V cavities for microleakage study prepared on 30 samples and Class II mesio-occluso-distal cavities for fracture resistance study on other 30 samples were prepared and randomly divided into three equal groups. Group I received amalgam, Group II received bonded amalgam, and Group III received composite resins. The microleakage was viewed under a stereomicroscope. The fracture resistance was evaluated using a universal testing machine. RESULTS: Bonded amalgam exhibited minimum microleakage, when compared to amalgam and composite resin and was found to be statistically insignificant (P = 0.203), while amalgam showed better fracture resistance compared to bonded amalgam and composite resin. It was found to be statistically insignificant (P = 0.144). CONCLUSIONS: Bonded amalgam appears to be comparable to amalgam when microleakage is considered and to composite resin when fracture resistance is considered; hence, bonded amalgam can also be an alternative material to amalgam in primary molars. PMID- 26672413 TI - Upper airway dimensions and sleep efficiency--three-dimensional imaging analysis and assessment of the nasopharyngeal appliance. AB - BACKGROUND: Reduction of upper airway (UA) dimensions during sleep is contemplated to cause reduced sleep efficiency (SE) but a definitive association is not affirmed. Efficacy of nasopharyngeal appliance (NPA) in management of UA resistance syndrome (UARS) has not been compared with mandibular repositioning splint (MRS). This study intended to assess relation of UA dimensions to SE and effectiveness of NPA. MATERIALS AND METHODS: Research had two phases: Case control study to determine association between UA and SE; randomized control trial (with independent concurrent trial groups and double-blind design) to analyze treatment outcome with NPA. Subjects were categorized to three groups of 20 in each: A control group of healthy subjects (Group A); two "Randomly Assigned" sample groups of subjects with reduced SE (Groups B and C). Preliminary questionnaire for sleep analysis, Final data collection sheet (first and second case sheets) were recorded, cephalometric variables analyzed, and diagnostic overnight polysomnography was done to match and confirm selection criteria. Three dimensional computed tomography was done to analyze airway dimensions before and after appliance placement. ANOVA and post-hoc tests were used for statistical analysis of results. CONCLUSIONS: Reduced UA dimension during sleep is associated with reduced SE; NPA gives better improvement for UARS than MRS. PMID- 26672414 TI - Evaluation of the efficacy of a probiotic drink containing Lactobacillus casei on the levels of periodontopathic bacteria in periodontitis: A clinico-microbiologic study. AB - BACKGROUND AND OBJECTIVES: This study was designed to evaluate whether the oral administration of lactobacilli could change the bacterial population in subgingival plaque. SUBJECTS AND METHODS: Forty-two healthy volunteers with chronic generalized mild to moderate periodontitis were given a probiotic drink containing Lactobacillus casei for 1 month. Subgingival plaque samples were collected at baseline, after which the patients were asked to consume the probiotic drink once daily for 1 month. At the 1 month interval, plaque samples were collected, and the drink discontinued. The patients were recalled at 2 months interval for collection of the final samples. The bacterial amounts in the plaque samples were analyzed by multiplex polymerase chain reaction procedure. RESULTS: Of the three periodontopathic bacteria selected, Porphyromonas gingivalis showed highly significant reductions in the bacterial levels at 1 month and 2 months intervals. In comparison, Aggregatibacter actinomycetemcomitans, when present higher than 10 * 10(3) at baseline, and Prevotella intermedia present higher than 2 * 10(3) at baseline, showed moderately significant reduction in their numbers. INTERPRETATION AND CONCLUSION: Oral administration of the probiotic lactobacilli reduced the numerical sum of the three selected periodontopathic bacteria and could contribute to the beneficial effects on periodontal conditions. PMID- 26672415 TI - Soft tissue facial profile in Himachal population: A photogrammetric analysis. AB - INTRODUCTION: Craniofacial growth of the skeleton and soft tissue influences the final configuration of occlusion and overall facial esthetics. MATERIALS AND METHODS: Two hundred samples were taken from Himachali ethnic population with age ranging from 18 to 28 years. The records will then be scaled to life size and landmarks will be located on the digitized image to obtain all linear and angular measurements. RESULTS: The parameters were analyzed using SPSS Statistics Software version 11.5. Student's t-test was conducted for comparison between male and female subjects. The reproducibility of the measurements was analyzed using Dahlberg's (1940) formula. To determine the difference between two measurements, made at least 2 months apart, 25 randomly selected records were redigitized. CONCLUSION: Himachali males and females show considerable sexual dimorphism with less prominent nose, less protrusive lower lip, and more chin height in males whereas females had more convex profile, less protrusive upper lip, and more tipped nose. PMID- 26672416 TI - Anti-microbial efficacy of Allium sativum extract against Enterococcus faecalis biofilm and its penetration into the root dentin: An in vitro study. AB - INTRODUCTION: Sodium hypochlorite (NaOCl) has long been the most preferred root canal irrigant in endodontic treatment, but besides being an effective anti microbial agent, it is highly cytotoxic. Thus, a search for an alternative herbal irrigant which would be more biocompatible but equally effective led to this study. AIM: To assess the anti-microbial efficacy of garlic extract (GE) against Enterococcus faecalis biofilm and its ability to penetrate into root dentin. MATERIALS AND METHODS: E. faecalis was cultured and treated with the test agents- normal saline, 5.25% of NaOCl, and the three different concentrations of GE (10%, 40%, and 70%). The experiment was done in four groups namely, 24-h Co-treatment group, 24-h biofilm treatment group, 1-week biofilm group, and 3-week biofilm group. These groups were subjected to microbial viability assay and fluorescence microscopic analysis. The most effective concentration of garlic (70%) was further tested and compared with 5.25% NaOCl for its dentin penetration property using 0.2% alizarin red under a fluorescence microscope. RESULTS: The findings revealed that GE was able to disrupt as well as prevent the formation of biofilm produced by E. faecalis. All the concentrations of GE displayed considerable anti microbial efficacy where 70% concentration was most effective and exhibited similar anti-microbial efficacy as 5.25% NaOCl. In terms of dentin penetration, no significant difference was found between GE and NaOCl. CONCLUSION: The results indicate that GE has a potential to serve as an alternative herbal root canal irrigant being an effective and biocompatible anti-microbial agent with good dentinal penetration property. PMID- 26672417 TI - Qualitative and quantitative analysis of palmar dermatoglyphics among smokeless tobacco users. AB - CONTEXT: Palm prints formed once does not change throughout life and is not influenced by environment. Palmar Dermatoglyphics can indicate the development of potentially malignant and malignant lesions and help in identifying persons at high risk of developing Oral submucous fibrosis (OSMF) and Oral squamous cell carcinoma (OSSC). AIM: To analyze the qualitative [finger ridge pattern and presence or absence of hypothenar pattern] and quantitative [mean ATD angle and total AB ridge count] variations in Palmar Dermatoglyphics in patients suffering from OSMF and OSCC. SETTINGS AND DESIGN: A prospective comparative study among 40 patients (Group I--10 samples of smokeless tobacco users with OSMF, Group II--10 samples of smokeless tobacco users with OSCC, Group III--10 samples of smokeless tobacco users without OSMF or OSCC and Group IV--10 samples without smokeless tobacco habit without OSMF and OSCC as controls) were selected. MATERIALS AND METHODS: The palm prints were recorded using an HP inkjet scanner. The patients were asked to place the palm gently on the scanner with the fingers wide apart from each other. The images of the palm prints were edited and qualitative and quantitative analysis were done. STATISTICAL ANALYSIS USED: Statistical analysis such as Kruskal Wallis, Post Hoc and Analysis of Varience were done. RESULTS: A highly significant difference among the finger ridge, hypothenar pattern and mean ATD angle (P<0.001) and total AB ridge count (P=0.005) in OSMF and OSCC patients were obtained. There is predominance of arches and loops, presence of hypothenar pattern, decrease in mean ATD angle and total AB ridge count in OSMF and Oral Cancer patients. CONCLUSION: Palmar Dermatoglyphics can predict the probable occurrence of OSMF and OSCC in smokelees tobacco users. PMID- 26672418 TI - Lingual frenulum and malocclusion: An overlooked tissue or a minor issue. AB - CONTEXT: Tongue-tie (more formally known as ankyloglossia) is a congenital anomaly characterized by an abnormally short lingual frenulum, which may restrict mobility of the tongue tip impairing its ability to fulfill its functions. The clinical significance of ankyloglossia is varied; rarely symptomatic to a host of problems including infant feeding difficulties, speech disorders, malocclusions, and others. AIMS: The need of this study was to evaluate the occurrence and severity of tongue-tie and its association with the type of malocclusions in two populations and also to correlate the various malocclusion traits with the grades of tongue-tie. SUBJECTS AND METHODS: A total of 700 school children in the age group of 9-17 years were examined for the presence of tongue-tie, 350 from regular schools and 350 from special schools. The presence was evaluated, measured, and graded into Grades I-V according to Kotlow's method. The malocclusion was assessed according to Angle's classification. Severity of crowding was assessed by Little's irregularity index in each case. Various other malocclusion traits were visually assessed, in relation to the positions of the teeth. STATISTICAL ANALYSIS USED: Spearman's rank correlation method was used to test the relationship between type of malocclusions, grades of tongue-tie and severity of crowding. Significance was considered at the (P < 0.05) level. RESULTS: Statistically significant differences were seen between grades of tongue tie and Angle's types of malocclusion and Spearman's correlation between them showed negative correlation. The Spearman's correlation showed a negative correlation between tongue-tie grades and severity of crowding. CONCLUSIONS: As the grade of tongue-tie increased, its association with Classes I and II malocclusion decreased. The lower grades of tongue-tie are associated with increased lower incisor crowding. Shorter, tight frenulums are more associated with maxillary constriction, anterior open bite, and spacing of the lower anteriors. PMID- 26672419 TI - Oral health status and treatment need among institutionalized elderly in India. AB - AIM: To assess the oral health status and treatment needs among elderly people aged 60 years and above residing as inmates in the old age homes of Hyderabad and Secunderabad, Andhra Pradesh, India. SETTINGS AND DESIGN: A cross-sectional study was performed to determine the oral health status and treatment needs among elderly people. MATERIALS AND METHODS: In order to assess the oral health status and treatment needs, the clinical assessment of oral mucosa, community periodontal index, loss of attachment, dentition status and treatment need, prosthetic status and prosthetic need was recorded based on a modified World Health Organization 1997 proforma. STATISTICAL ANALYSIS USED: Multi-group analysis was done using analysis of variance. P < 0.05 was considered statistically significant. RESULTS: Of the 812 inmates, 431 (64.0%) of the study participants had oral mucosal lesions. In terms of periodontal status, all sextants were excluded (Code "X") in 324 (39.9%) subjects. Out of dentate population, a majority of the inmates (219; 27.0%) presented with deep pockets (Code "4") followed by shallow pockets (Code "3"--183; 22.5%). The majority of the subjects had no prosthesis in the upper arch (85.0%) and lower arch (86.6%). CONCLUSION: The study demonstrated poor oral health among institutionalized elderly inmates. Oral mucosal lesions were found to be higher and periodontal status was also poor amongst the study population. PMID- 26672420 TI - Estimation of high sensitivity C-reactive protein in patients with periodontal disease and without coronary artery disease. AB - BACKGROUND: HsCRP (Highly sensitive C reactive protein) is a global indicator for future vascular events in adults detected in blood stream 48 hours before the cardiovascular event. Periodontal disease may increase blood levels of inflammatory markers like IL-6, CRP and HsCRP. Hence the aim of the present study is to evaluate the presence of elevated HsCRP levels in chronic periodontitis patients. MATERIAL AND METHODS: 100 patients who reported for cardiac master health check up were enrolled in the study. The periodontal status was assessed using periodontal probing pocket depth and clinical attachment level. The decayed, missing and filled tooth was recorded using DMFT index. The venous samples of these patients were obtained for recording HsCRP levels. RESULTS: Pearson correlation was used to analyze the relationship between HsCRP level and probing pocket depth, clinical attachment loss and DMFT. The correlation value was 0.051, 0.025 and 0.101 respectively, the correlation is statistically significant for probing pocket depth and clinical attachment level (P>0.05). Chi square test was performed to study the association between gender and HsCRP, Diabetes Mellitus and HsCRP and Hypertension and HsCRP; the results showed that there is no significant association between any of the above mentioned factors and HsCRP level in blood. CONCLUSIONS: We found an increased level of HsCRP in patients with chronic periodontitis which revealed the susceptibility of these patients to cardiac diseases like myocardial infarction and stroke. Hence present day focus in the line of management of cardiac patient has changed from the periodontal perspective. PMID- 26672421 TI - Comparative clinical evaluation of glycosylated haemoglobin level in healthy and chronic periodontitis patients: A chairside diagnostic method. AB - OBJECTIVE AND BACKGROUND: Glycosylated haemoglobin (HbA1c) level can consequently be interpreted as an average of the blood glucose present over the past 3-4 months. Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine the level of HbA1c in healthy and periodontitis patients who were previously not diagnosed with diabetes mellitus. MATERIALS AND METHODS: A total of 40 patients were selected for study and divided into two groups. Group 1 included patients with a healthy periodontium, and Group 2 included patients suffering from chronic periodontitis. Finger stick blood was collected by special collection unit (A1CNOW+(r) Bayer Health Care, Tarrytown New York, USA), for estimating level of HbA1c. RESULT: Both groups showed similar HbA1c levels clinically with slight increase in levels in the test group, but was statistically significant (test--5.66 +/- 0.35%, control--5.17 +/- 0.3% P = 0.003). CONCLUSION: Indians are at a high-risk of developing periodontitis and diabetes. These data suggest a possible link between periodontitis and glycemic control in nondiabetic individuals, periodontal disease may be a potential contributor to the development of type 2 diabetes. PMID- 26672422 TI - Effect of mouthrinses with different active agents in the prevention of initial dental erosion. AB - INTRODUCTION: Hydrochloric acid (HCl) from the gastric juice is the only source of intrinsic acid, which can reach the oral cavity in cases of gastroesophageal reflux or chronic vomiting, enhancing the risk of dental erosion. AIM: Compare the effects of mouthrinses with different active agents in the prevention of initial dental erosion caused by HCl. SUBJECTS AND METHODS: Casein (CAS at 0.2%), sodium hexametaphosphate (HMP at 0.02%), titanium tetrafluoride (TiF4 at 0.34%), and stannous fluoride (SnF2 at 0.87%) were individually added to an experimental mouthrinse. The mouthrinse without additives was used as the negative control (C) and a commercially available mouthrinse for erosion (ELM-Elmex(r)) as the reference product. Enamel specimens were exposed to human saliva and randomly assigned to 6 experimental groups (n = 8). Specimens were submitted to erosion in HCl for 10 s, followed by to the experimental mouthrinses for 30 s, and artificial saliva for 60 min. This cycle was repeated 3 times. The total amounts of calcium and phosphorus released by the specimens in the 2nd and 3rd erosive challenges were evaluated by atomic emission spectrometry. Statistical analysis used Shapiro-Wilks and Hartley tests, followed by one-way ANOVA and Tukey tests. RESULTS: When compared with C, ELM and HMP presented significantly less calcium in solution, with no difference between them. All the groups showed similar and significantly less phosphorus than C, except CAS. CONCLUSIONS: HMP was the only agent that could match the protection against initial erosion of the commercially available mouthrinse in both analyses. PMID- 26672423 TI - Comparative evaluation of tensile bond strength of silicone-based denture liners after thermocycling and surface treatment. AB - PURPOSE: To examine, evaluate, and compare the tensile bond strength of two silicone-based liners; one autopolymerizing and one heat cured, when treated with different chemical etchants to improve their adhesion with denture base resin. MATERIALS AND METHODS: Hundred and sixty test specimens of heat-cured polymethyl methacrylate (PMMA) were fabricated; out of which 80 specimens were tested for tensile bond strength after bonding it to autopolymerizing resilient liner (Ufigel P) and rest 80 to heat-cured resilient liner (Molloplast B). Each main group was further divided into four subgroups of 20 specimens each, one to act as a control and three were subjected to surface treatment with different chemical etchants namely dichloromethane, MMA monomer, and chloroform. The two silicone based denture liners were processed between 2 PMMA specimens (10 mm * 10 mm * 40 mm) in the space provided by a spacer of 3 mm, thermocycled (5-55 degrees C) for 500 cycles, and then their tensile strength measurements were done in the universal testing machine. RESULTS: One-way ANOVA technique showed a highly significant difference in the mean tensile bond strength values for all the groups. The Student's t-test computed values of statistics for the compared groups were greater than the critical values both at 5% and at 1% levels. CONCLUSION: Surface treatment of denture base resin with chemical etchants prior to the application of silicone-based liner (Ufigel P and Molloplast-B) increased the tensile bond strength. The increase was the highest with specimens subjected to 180 s of MMA surface treatment and the lowest with control group specimens. PMID- 26672424 TI - Effectiveness of different formulations of Endo-PTC to promote root canal cleaning. AB - CONTEXT: Endo-PTC are used during endodontic treatment; however, until now no study evaluated the cleaning of dentin walls after use of different Endo-PTC formulations. AIMS: The aim of this study was to assess qualitatively, by means of scanning electron microscopy (SEM) images, the cleaning of dentin walls of root canals after chemomechanical preparation (CMP) using Endo-PTC cream and Endo PTC light associated to 2.5% sodium hypochlorite and 17% ethylenediamine tetraacetate (EDTA). MATERIALS AND METHODS: Forty single-rooted human maxillary central incisors with straight canals and fully formed apex were selected. The specimens were randomly divided into four groups depending on the type of Endo PTC and the final rinse with 17% EDTA. After CMP, all specimens were sectioned and processed for observation of the apical thirds by using SEM. Three calibrated evaluators attributed scores to each specimen. STATISTICAL ANALYSIS USED: The differences between irrigation protocols were analyzed with Kruskal-Wallis test followed by Bonferroni adjustment for multiple comparisons. The significance level was set at alpha = 0.05. RESULTS: The use of Endo-PTC cream or Endo-PTC light did not influence the smear-layer (SL) removal (P > 0.05). When EDTA were used, it was obtained the best cleaning results with no significant difference between the substances (P < 0.05). CONCLUSIONS: It can be concluded that EDTA is essential to promote SL removal which was not affected by the type of Endo-PTC formulation. PMID- 26672425 TI - An in vitro evaluation of antimicrobial activity of five herbal extracts and comparison of their activity with 2.5% sodium hypochlorite against Enterococcus faecalis. AB - CONTEXT: Sodium hypochlorite is the most widely used irrigant in endodontic practice, but it has various disadvantages. Literature has shown that herbal products such as Propolis, Azadirachta indica (AI), Triphala, Curcuma longa, and Morinda citrifolia (MC) possess good antimicrobial properties and thus can be used as potential endodontic irrigants. AIM: To evaluate and compare the antimicrobial activity of five herbal extracts, i.e., Propolis, AI, Triphala, C. longa, and MC with that of 2.5% sodium hypochlorite against Enterococcus faecalis. MATERIALS AND METHODS: E. faecalis American Type Culture Collection 21292 was inoculated onto brain heart infusion agar plate. Discs impregnated with herbal medicaments were placed on the inoculated plates and incubated at 37 degrees C aerobically for 24 h and growth inhibition zones were measured. STATISTICAL ANALYSIS: Mean zone of inhibition in descending order was found as sodium hypochlorite > Propolis > AI > Triphala > C. longa = MC > ethanol. Statistical analysis was performed using one-way analysis of variance which showed a significant difference in the zone of inhibition of sodium hypochlorite and Propolis (P < 0.001). RESULTS: Propolis showed highest zone of inhibition among all the herbal extracts next to sodium hypochlorite. CONCLUSION: Propolis and AI have significant antimicrobial activity against E. faecalis. PMID- 26672426 TI - Antimicrobial and antifungal efficacy of Spilanthes acmella as an intracanal medicament in comparison to calcium hydroxide: An in vitro study. AB - BACKGROUND: Repeated endodontic failures are due to pathogens like Enterococcus faecalis and Candida albicans which are resistant to the common intracanal medicaments like calcium hydroxide (Ca[OH]2). AIMS: To determine the role of commonly used folk medicine, Spilanthes acmella (SPA) against root canal pathogens like E. faecalis, C. albicans, Staphylococcus aureus, Streptococcus sp, and to compare its efficacy with Ca(OH)2, a popularly used intracanal medicament. MATERIALS AND METHODS: Bacterial strains of S. aureus, Streptococcus sp., E. faecalis, and fungal strains of C. albicans were tested against different concentrations of SPA and Ca(OH)2. Seven days old cultures of test organisms were seeded onto agar plates and uniformly spread with a spreader. Five to six wells (8 mm) were made on agar plate to which different concentrations of the test solutions were added. The inoculated plates were kept in an incubator at 37 degrees C for 48 h and inhibition zones were measured. STATISTICAL ANALYSIS: Results of SPA were compared with results of Ca(OH)2 statistically using Mann Whitney U test. RESULTS: A significant zone of inhibition was obtained with SPA and was found to increase as the concentration increased for C. albicans. SPA showed a significant zone of inhibition at 2-5% and 10% whereas Ca(OH)2 showed a zone of inhibition only at 10% for E. faecalis. SPA showed a zone of inhibition only at 10%, whereas, Ca(OH)2 showed a significant zone of inhibition at 5% and 10% for S. aureus and Streptococcus sp., respectively. CONCLUSION: SPA possesses remarkable antibacterial and antifungal activity against common root canal pathogens which are responsible for repeated endodontic failures such as E. faecalis and C. albicans when compared with medicaments like Ca(OH)2. PMID- 26672427 TI - In vitro antibacterial activity of ethanolic extract of Morus alba leaf against periodontal pathogens. AB - CONTEXT: Antibiotic resistance is a major problem with inadvertent usage. Thus, there is a need to search for new antimicrobial agents of herbal origin to combat antibiotic resistance. One such plant is Morus alba which has a long history of medicinal use in traditional Chinese medicine. AIM: To compare the antibacterial activity of ethanolic extract of M. alba leaves with chlorhexidine gluconate against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia. SETTINGS AND DESIGN: Experimental in vitro study. METHODOLOGY: Crude extract from the leaves of M. alba were prepared by Soxhlet extraction method by using ethanol as a solvent. Minimum inhibitory concentration (MIC) of the extract was assessed against A. actinomycetemcomitans, P. gingivalis and T. forsythia, and compared with that of chlorhexidine gluconate by broth dilution method. RESULTS: P. gingivalis was the most sensitive organism against the M. alba extract with an MIC value of 1.95 mg/ml; while T. forsythia and P. gingivalis both were most sensitive organisms against chlorhexidine gluconate with MIC values of 0.00781 mg/ml. CONCLUSION: M. alba possess good antibacterial activity against A. actinomycetemcomitans, P. gingivalis and T. forsythia and thus would be beneficial for the prevention and treatment of periodontal disease. However, chlorhexidine gluconate was found to be more effective when compared to M. alba. PMID- 26672428 TI - Prevalence of oral mucosal lesions among chewing tobacco users: A cross-sectional study. AB - CONTEXT: The increasing use of chewing tobacco (CT) in the last 10-12 years has led to an increased incidence of potentially malignant oral disorders and frank oral malignancies. AIM: To determine the frequency of oral mucosal lesions and to correlate the dose-response relationship among CT users of Bengaluru North province. SETTINGS AND DESIGN: This population-based cross-sectional study was conducted among a randomized cluster sample of adults in low-income group (slums), of Bengaluru North, Karnataka state, India. MATERIALS AND METHODS: Nine hundred and one subjects, all CT users were surveyed in this cross-sectional study. A prestructured questionnaire which included information on type and amount of CT used, duration and frequency of use, and location of placement of tobacco in the oral cavity was used for assessment, which was followed by oral examination for the presence of lesions. STATISTICAL ANALYSIS USED: Chi-square and Fisher's exact tests were used to assess the statistical significance. RESULTS: Of the 901 subjects with CT habits, 55.8% revealed no clinically detectable oral mucosal changes and 44.1% showed mucosal changes of which 63.8% were males and 36.1% were females. The most common finding was chewers mucositis (59.5%) followed by submucous fibrosis (22.8%), leukoplakia (8%), lichenoid reaction (6.5%), oral cancer (2.7%), and lichen planus (0.5%). CONCLUSION: This study provides information about different CT habits and associated mucosal lesions among this population. PMID- 26672429 TI - Fracture management of an edentulous mandible in a geriatric osteoporotic patient. AB - Fracture of an edentulous mandible is a difficult task primarily due to the absence of teeth. The management becomes even more difficult if the patient is geriatric and osteoporotic. A simple technique of using bite block splint, maxillomandibular fixation screws, and intermaxillary fixation has been presented to enable healing of fracture of mandible in such cases. The technique, which crosses the boundaries of conventional fracture management provides, promising results with minimum morbidity thus imparting optimum quality of life ahead for the patient. PMID- 26672430 TI - Dens evaginatus and dens invaginatus in a double tooth: A rare case report. AB - The presence of dens invaginatus (DI) and dens evaginatus (DE) on same tooth is a rare phenomenon. However, when these dental anomalies occur on a double tooth, it becomes an extremely rare phenomenon. The authors report a rare case of DI and DE on fused permanent maxillary central incisor with supernumerary tooth in a 40 year-old male. The present article also focuses on the differentiating fusion from gemination and also reviews preventive and management strategies for tooth with complex dental anatomy. PMID- 26672431 TI - Surgical management of necrotizing sialometaplasia of palate. AB - Necrotizing sialometaplasia (NSM) is a rare benign, inflammatory disease of both major and minor salivary glands, although more commonly reported in the minor glands of the palate. The characteristic clinical presentation can perplex the clinician and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. The clinical and histological similarity between this entity and a malignant lesion may result in unnecessary or mis-treatment. Though clinically mimics malignancy, NSM is considered to be a self-limiting disease, and takes about 3-12 weeks to resolve. Majority of the case resolves itself or by supportive and symptomatic treatment. Surgical intervention is rarely required in NSM except the diagnostic biopsy. Herein we report the clinical, histopathological feature and surgical management of a case of NSM of hard palate in a young adult male. PMID- 26672432 TI - Time trend 2000-2013 of vitamin D status in older people who sustain hip fractures: steps forward or steps back? A retrospective study of 1599 patients. AB - BACKGROUND: Substantial proportions of hip-fracture patients have very low serum levels of 25-hydroxyvitamin D, which can negatively affect rehabilitation. However, it is not known whether changes in vitamin D deficiency have occurred over the last years in the patients who sustain hip fractures. AIM: To assess time trend 2000-2013 of calcifediol serum levels in the hip-fracture patients admitted to our rehabilitation division. DESIGN: Retrospective observational study. SETTING: A rehabilitation hospital division. POPULATION: A number of 1599 inpatients with a hip fracture admitted between January 1, 2000 and December 31, 2013 to our rehabilitation division. METHODS: A blood sample was collected in the morning following an overnight fasting 14.4+/-4.4 (mean+/-SD) days after surgery. We assessed 25-hydroxyvitamin D levels by an immunoenzymatic assay. RESULTS: Calcifediol levels increased till 2006-2007 and decreased afterward. In 2006 2007, the median 25-hydroxyvitamin D level (13.1 ng/mL, interquartile range 7.9 25ng/mL) was significantly higher (P<0.001) than the one found in both the periods 2000-2001 (5.4 ng/mL, interquartile range 3.5-9 ng/mL), and 2012-2013 (7ng/mL, interquartile range 5-14 ng/mL). In the last two-year period of observation (2012-2013), 25-hydroxyvitamin D levels were slightly higher (P<0.001) than in the first one (2000-2001). The association between periods of observation and 25-hydroxyvitamin D levels persisted after adjustment for age, BMI, and sex (P<0.001). CONCLUSIONS: A significant increase in calcifediol concentrations was seen till 2006-2007, but a significant decrease was observed afterward. Finally, calcifediol levels were only slightly higher in the last two years of observation than in the first two years and severe vitamin D deficiency was common during the whole 14-year study period. CLINICAL REHABILITATION IMPACT: Heightened awareness is needed to prevent and treat vitamin D deficiency in hip fracture patients. PMID- 26672433 TI - Unprotected distal left main bifurcation drug eluting stent restenosis: first successful experience with simultaneous kissing balloon dilatation using sirolimus coated balloon. AB - Treatment of unprotected left main (ULM) in-stent restenosis (ISR) in patients with prior drug eluting stent implantation is challenging. Treatment usually involves complex stenting procedures or bypass grafting. Drug coated balloon (DCB) is relatively new concept which is usually used in treatment of ISR. In a patient of ULM ISR, use of DCBs is a safe, economic and a technically simple option with relatively good outcomes. We report use of simultaneous kissing balloon dilatation with novel sirolimus coated balloons (SCBs) via radial artery to treat ULM ISR. PMID- 26672434 TI - Ultrasound assessment of selected peripheral nerve pathologies. Part III: Injuries and postoperative evaluation. AB - The previous articles of the series devoted to ultrasound diagnostics of peripheral nerves concerned the most common nerve pathologies, i.e. entrapment neuropathies. The aim of the last part of the series is to present ultrasound possibilities in the postoperative control of the peripheral nerves as well as in the diagnostics of the second most common neuropathies of peripheral nerves, i.e. posttraumatic lesions. Early diagnostics of posttraumatic changes is of fundamental importance for the course of treatment and its long-term effects. It aids surgeons in making treatment decisions (whether surgical or conservative). When surgical treatment is necessary, the surgeon, based on US findings, is able to plan a given type of operative method. In certain cases, may even abandon the corrective or reconstructive surgery of the nerve trunk (when there are extensive defects of the nerve trunks) and instead, proceed with muscle transfers. Medical literature proposes a range of divisions of the kinds of peripheral nerve injuries depending on, among others, the mechanism or degree of damage. However, the most important issue in the surgeon-diagnostician communication is a detailed description of stumps of the nerve trunks, their distance and location. In the postoperative period, ultrasound is used for monitoring the operative or conservative treatment effects including the determination of the causes of a persistent or recurrent neuropathy. It facilitates decision-making concerning a repeated surgical procedure or assuming a wait-and-see attitude. It is a difficult task for a diagnostician and it requires experience, close cooperation with a clinician and knowledge concerning surgical techniques. Apart from a static assessment, a dynamic assessment of possible adhesions constitutes a crucial element of postoperative examination. This feature distinguishes ultrasound scanning from other methods used in the diagnostics of peripheral neuropathies. PMID- 26672435 TI - Characterization of Biochemical Cartilage Change After Anterior Cruciate Ligament Injury Using T1rho Mapping Magnetic Resonance Imaging. AB - BACKGROUND: Patients with anterior cruciate ligament (ACL)-injured knees are at an increased risk of posttraumatic osteoarthritis (OA). OA changes secondary to ACL injuries have many variations, and when and where early cartilage degenerative change begins has not yet been established. PURPOSE: To characterize the location of cartilage degeneration after ACL injury associated with time since injury using T1rho (T1rho) mapping. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: In this study, 49 knees with ACL injuries and 14 normal knees from uninjured volunteers were imaged with a 3.0-T magnetic resonance scanner. Three regions of interest (ROIs) were defined in the cartilage at the weightbearing area of the femoral condyles (anterior, middle, and posterior zones). Two ROIs were defined in the tibial plateau (anterior and posterior zones). The T1rho values within the ROIs were measured. Patients were allocated into 3 groups based on time since injury: <12 weeks (group A; 28 patients), 12 weeks to 2 years (group B; 14 patients), and >2 years to 5 years (group C; 7 patients). RESULTS: Mean T1rho values were significantly greater in the anterior and middle ROIs of the medial femoral condyle in group C compared with those in other groups (P < .05). Patients with medial meniscus injury, for whom the time since injury was >=12 weeks, exhibited significantly greater T1rho values in the middle areas of the medial femoral condyle versus normal knees and ACL-injured knees without medial meniscus injury. CONCLUSION: The risk of cartilage degeneration in the area of the femoral condyle that contacts the tibia during small degrees of flexion increased when the time since injury was longer than 2 years. In addition, medial meniscus injury was associated with cartilage degeneration at the medial femoral condyle in the chronic phase. CLINICAL RELEVANCE: Cartilage degeneration occurs more than 2 years after ACL injury and increases with medial meniscus injury. Early intervention may be desirable for meniscus injury. PMID- 26672437 TI - Factors Contributing to Acute Kidney Injury and the Impact on Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) patients are at a high risk of acute kidney injury (AKI). This study aimed to investigate AKI and the relationship with iodinated contrast media (ICM), whether there are significant pre- or peri- procedural variables predicting AKI, and whether AKI impacts on hospital length of stay and mortality. METHODS: Serum creatinine (SC) levels pre- and post- (peak) TAVR were recorded in 209 consecutive TAVR patients. AKI was defined by the Valve Academic Research Consortium 2 (VARC2) criteria. Baseline characteristics, procedural variables, hospital length of stay (LOS) and mortality at 72hours, 30 days and one year were analysed. RESULTS: Eighty-two of 209 (39%) patients suffered AKI. Mean ICM volume was 228cc, with no difference between patients with AKI and those with no AKI (227cc (213-240(95%CI)) vs 231cc (212-250) p=0.700)). Univariate and multivariate analysis demonstrated that chronic kidney disease, respiratory failure, previous stroke, the need for blood transfusion and valve repositioning were all predictors of AKI. Acute kidney injury increased LOS (5.6 days (3.8 - 7.5) vs 3.2 days (2.6 - 3.9) no AKI (P=0.004)) but was not linked to increased mortality. Mortality rates did increase with AKI severity. CONCLUSION: Acute kidney injury is a common complication of TAVR. The severity of AKI is important in determining mortality. Acute kidney injury appears to be independent of ICM use but pre-existing renal impairment and respiratory failure were predictors for AKI. Transcatheter aortic valve replacement device repositioning or retrieval was identified as a new risk factor impacting on AKI. PMID- 26672438 TI - Reply to: "Yildirim B, Biteker FS. Forgotten Predictors of Prosthetic Valve Endocarditis. Heart Lung Circ. 2015". PMID- 26672436 TI - Variation in Arterial Access for Invasive Coronary Procedures in New Zealand: A National Analysis (ANZACS-QI 5). AB - BACKGROUND: Radial arterial access (RA) and femoral arterial access (FA) rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. METHODS AND RESULTS: Patient characteristics, procedural details, and inpatient outcome data were collected in the All New Zealand Acute Coronary Syndrome - Quality Improvement (ANZACS-QI) registry on consecutive patients undergoing ICA over five months. Of the 5894 ICAs 81% were via RA. Hospitals averaged 25 - 176 procedures/month (46.5% - 96.4% via RA). Operators averaged 17 procedures/month. Those performing more than 20 ICAs/month had RA rates between 61% - 99%. Of the 75 operators, 69% met the ESC recommendation. After multivariable adjustment higher operator (RR 1.12, CI 1.09 - 1.30) and hospital (RR 1.21, CI 1.15 - 1.28) volume were independent predictors of RA. Those with prior CABG (RR 0.51, CI 0.45 - 0.57), STEMI <12h (RR 0.91, CI 0.87 - 0.96), and female sex (RR 0.96, CI 0.94 - 0.99) were less likely to receive RA. CONCLUSIONS: New Zealand has a high RA rate for ICAs. Rates vary substantially between both operators and centres. Radial arterial was highest amongst the highest volume operators and centres. PMID- 26672439 TI - Knuckle pads - a rare finding. AB - Knuckle pads are rare harmless subcutaneous nodules that must be differentiated from joint disease of the proximal interphalangeal or rarely of the metacarpophalangeal joints as well as from other masses of the paraarticular tissues. We present a case of an otherwise healthy 36-year-old woman presenting with bilateral knuckle pads located at the dorsal aspect of the proximal interphalangeal joints. No predisposition to a specific musculoskeletal disorder was noted. Ultrasound revealed well-delimited subcutaneous hypoechoic masses without internal flow signals at color Doppler. Histology showed proliferation of myofibroblasts with a decrease of elastic filaments in the deep dermis. The clinical picture, the family history in addition to the histology allowed us to make the diagnosis of knuckle pads. We present the ultrasound findings of knuckle pads and discuss the differential diagnosis of a "swelling" in the dorsal region of proximal interphalangeal joints and metacarpophalangeal joints. PMID- 26672440 TI - Synthesis and decomposition of Li3Na(NH2)4 and investigations of Li-Na-N-H based systems for hydrogen storage. AB - Previous studies have shown modified thermodynamics of amide-hydride composites by cation substitution, while this work systematically investigates lithium sodium-amide, Li-Na-N-H, based systems. Li3Na(NH2)4 has been synthesized by combined ball milling and annealing of 3LiNH2-NaNH2 with LiNa2(NH2)3 as a minor by-product. Li3+xNa1-x(NH2)4 releases NaNH2 and forms non-stoichiometric Li3+xNa1 x(NH2)4 before it melts at 234 degrees C, as observed by in situ powder X-ray diffraction. Above 234 degrees C, Li3+xNa1-x(NH2)4 releases a mixture of NH3, N2 and H2 while a bi-metallic lithium sodium imide is not observed during decomposition. Hydrogen storage performances have been investigated for the composites Li3Na(NH2)4-4LiH, LiNH2-NaH and NaNH2-LiH. Li3Na(NH2)4-4LiH converts into 4LiNH2-NaH-3LiH during mechanochemical treatment and releases 4.2 wt% of H2 in multiple steps between 25 and 340 degrees C as revealed by Sievert's measurements. All three investigated composites have a lower peak temperature for H2 release as compared to LiNH2-LiH, possibly owing to modified kinetics and thermodynamics, due to the formation of Li3Na(NH2)4 and LiNa2(NH2)3. PMID- 26672441 TI - Surprising coordination for low-valent actinides resembling uranyl(vi) in thorium(iv) organic hybrid layered and framework structures based on a graphene like (6,3) sheet topology. AB - Three thorium(iv)-based metal-organic hybrid compounds with 2D layered and 3D framework structures exhibiting graphene-like (6,3) sheet topologies were prepared with linkers with threefold symmetry. These compounds contain rare and relatively anisotropic coordination environments for low-valent actinides that are similar to those often observed for high-valent actinide ions. PMID- 26672442 TI - Mutational analysis of the hyc-operon determining the relationship between hydrogenase-3 and NADH pathway in Enterobacter aerogenes. AB - In this study, the hydrogenase-3 gene cluster (hycDEFGH) was isolated and identified from Enterobacter aerogenes CCTCC AB91102. All gene products were highly homologous to the reported bacterial hydrogenase-3 (Hyd-3) proteins. The genes hycE, hycF, hycG encoding the subunits of hydrogenase-3 were targeted for genetic knockout to inhibit the FHL hydrogen production pathway via the Red recombination system, generating three mutant strains AB91102-E (DeltahycE), AB91102-F (DeltahycF) and AB91102-G (DeltahycG). Deletion of the three genes affected the integrity of hydrogenase-3. The hydrogen production experiments with the mutant strains showed that no hydrogen was detected compared with the wild type (0.886 mol/mol glucose), demonstrating that knocking out any of the three genes could inhibit NADH hydrogen production pathway. Meanwhile, the metabolites of the mutant strains were significantly changed in comparison with the wild type, indicating corresponding changes in metabolic flux by mutation. Additionally, the activity of NADH-mediated hydrogenase was found to be nil in the mutant strains. The chemostat experiments showed that the NADH/NAD(+) ratio of the mutant strains increased nearly 1.4-fold compared with the wild type. The NADH-mediated hydrogenase activity and NADH/NAD(+) ratio analysis both suggested that NADH pathway required the involvement of the electron transport chain of hydrogenase-3. PMID- 26672444 TI - Amino acid residues adjacent to the catalytic cavity of tetramer L-asparaginase II contribute significantly to its catalytic efficiency and thermostability. AB - L-Asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) catalyzes the hydrolysis of L-asparagine to L-aspartic acid and ammonia. It can be used to reduce the formation of acrylamide, which is carcinogenic to humans in foods, via removal of the precursor, asparagine, from the primary ingredients. However, low activity and poor thermostability of L-asparaginase restrict its application in food industry. In this study, we successfully improved thermostability and catalytic efficiency of L-asparaginase II (BsAII) from Bacillus subtilis B11-06 by site directed mutagenesis. According to sequences alignment and homologous modeling, residues G107, T109 and S166 which were adjacent to the catalytic cavity were selected and substituted by Asp, Gln/Ser and Ala, respectively, to construct mutants G107D, T109Q, T109S and S166A. The BsAII mutant of G107D (G107Dansz) displayed superior performance in thermal tolerance and higher activity than the wild-type enzyme (towards L-asparagine). Comparative analysis of hydrogen bond interactions, surface electrostatic potential and structure of substrate binding pocket between G107Danszand BsAII indicated that the substitution of G107, which was adjacent to catalytic cavity with Asp, resulted in small conformational changes and surface electrostatic potential redistribution and contributed to the improved protein stability and catalytic efficiency. PMID- 26672443 TI - Nutrient control for stationary phase cellulase production in Trichoderma reesei Rut C-30. AB - This work describes the use of nutrient limitations with Trichoderma reesei Rut C 30 to obtain a prolonged stationary phase cellulase production. This period of non-growth may allow for dependable cellulase production, extended fermentation periods, and the possibility to use pellet morphology for easy product separation. Phosphorus limitation was successful in halting growth and had a corresponding specific cellulase production of 5+/-2 FPU/g-h. Combined with the addition of Triton X-100 for fungal pellet formation and low shear conditions, a stationary phase cellulase production period in excess of 300 h was achieved, with a constant enzyme production rate of 7+/-1 FPU/g-h. While nitrogen limitation was also effective as a growth limiter, it, however, also prevented cellulase production. PMID- 26672446 TI - Modulation of the thermostability and substrate specificity of Candida rugosa lipase1 by altering the acyl-binding residue Gly414 at the alpha-helix-connecting bend. AB - Candida rugosa Lipase1 (LIP1) is widely used in industrial applications. Optimizing its catalytic performance is still a challenging goal for protein engineers. Mutagenesis of key residues in the active site of the enzyme may provide an effective strategy for enhancing stability and altering substrate specificity. In this study, multiple sequence alignment and structural analysis revealed that the acyl-binding residue, Gly414, of LIP1, which is located at a bend connecting alpha-helixes, was the non-conserved residue in five other isoenzymes. Using saturation mutagenesis, four mutants with improved stability (G414A, G414M, G414H and G414W) were obtained. Compared to the wild type, the best mutant (G414W) exhibited a remarkable 6.5-fold enhancement in half-life at 60 degrees C and a 14 degrees C higher T50(15). Its optimum temperature was increased by 15 degrees C. Simultaneously, G414W displayed a shift in substrate preference from medium-chain to short-chain pNP-ester. Modeling analysis showed that the multiple interactions formed by hydrophobic clusters and hydrogen bonds in the acyl-binding tunnel might lead to the observed thermostability improvement. Additionally, the bulky tryptophan substitution formed a strong steric hindrance to the accommodation of long-chain substrates in the tunnel. These results indicate that the key acyl-binding residues at the alpha-helix connecting bend could mediate enzyme stability and catalytic substrate spectra. PMID- 26672445 TI - Molecular and enzymatic characterization of alkaline lipase from Bacillus amyloliquefaciens E1PA isolated from lipid-rich food waste. AB - Bacillus amyloliquefaciens E1PA is a lipase-producing strain that was originally isolated from lipid-rich food waste, and the production of its lipase was found to be induced by vegetable oils. The E1PA lipase was successfully expressed and secreted in a heterologous Escherichia coli host and was ultimately purified. The conserved pentapeptide motif Ala-His-Ser-Met-Gly was observed at positions 108 112. The purified recombinant lipase was stable over a pH range of 4.0-11.0 at 40 degrees C and exhibited maximal activity at pH 10. The recombinant E1PA lipase hydrolyzed a wide range of acyl esters (C4-C18). However, the highest activity (3.5 units mg(-1)) was observed when the p-nitrophenyl ester of myristate (C14) was used as a substrate. Compared to the lipases produced by Bacillus spp., the E1PA lipase displayed a structural molecular mass excluding the leader sequence (19.22 kDa) and a pI (9.82) that were similar to those reported for B. amyloliquefaciens lipases and lipase subfamily I.4 but that were quite distinct from those of lipase subfamily I.5 (approximately 43 kDa, pI 6). These results suggested that Bacillus lipases are closely related. Although the recombinant E1PA lipase digested only certain oils, the wild-type E1PA lipase degraded a variety of oils, including blended and re-used cooking oils. The recombinant and wild-type forms of the E1PA lipase were able to digest heterogeneous lipid-rich food waste at similar levels; this result suggests that this lipase can function even when it solely consists of its structural enzyme component. The enzyme exhibited lipid hydrolysis ability as either an intracellular domain of the recombinant protein or an extracellular domain secreted by the E1PA strain. However, the recombinant lipase showed higher activity than the wild-type E1PA lipase, indicating that the recombinant protein from E. coli possessed effective lipase activity. Thus, the inducible alkaline E1PA lipase exhibited the ability to act on a broad spectrum of substrates, and the effective form produced in the heterogeneous host can be further developed for several applications, such as biodiesel production and lipase production. PMID- 26672447 TI - Quantitative enzymatic production of sialylated galactooligosaccharides with an engineered sialidase from Trypanosoma rangeli. AB - Sialylated galactooligosaccharides (GOS) represent a potential infant formula ingredient, which is believed to contribute with a combination of the beneficial properties of the prebiotic GOS as well as of sialylated human milk oligosaccharides. Sialylated GOS do not exist in natural milk, but can be produced from kappa(kappa)-casein glycomacropeptide (CGMP), a sialylated side stream component from cheese-making, by sialidase-catalyzed transsialylation. Using a rationally designed mutant of the sialidase from Trypanosoma rangeli, Tr13, with enhanced transsialylation activity, six different GOS preparations with a varying degree of polymerization (DP) were effectively sialylated with molar yields of 20-30% on the CGMP sialyl in batch reactions. The rate of sialylation of the individual DPs was largely dependent on the DP distribution in each GOS preparation, and Tr13 catalysis did not discriminate against large GOS molecules, providing the novelty point that GOS molecules are sialylated independently of their size by Tr13. Using CGMP, GOS, and Tr13, the production of gram-scale quantities of sialyl-GOS was achieved in 20L volume reactions. Compared to the benchmark transsialidase from pathogenic Trypanosoma cruzi, the Tr13 was significantly more thermostable. By employing an enzymatic membrane reactor, Tr13 could be recycled and after seven consecutive 1-h reaction cycles, the biocatalytic productivity of the enzyme was increased 7-fold compared to the batch reaction. Assuming that the enzyme may be specific for alpha-2,3-bound sialyl moieties only, and that only 50% of sialyl linkages in CGMP are alpha-2,3 linked, the molar yield of sialyl-GOS on the available alpha-2,3-bound sialyl moieties in CGMP reached 80% in the enzymatic membrane reactor system. PMID- 26672448 TI - Selective production of 1-monocaprin by porcine liver carboxylesterase-catalyzed esterification: Its enzyme kinetics and catalytic performance. AB - Porcine liver carboxylesterase (PLE) belongs to carboxylesterase family (EC 3.1.1.1) as a serine-type esterase. The PLE-catalyzed esterification of capric acid with glycerol in reverse micelles was investigated on the catalytic performance and enzyme kinetics. The most suitable structure of reverse micelles was comprised of isooctane (reaction medium) and bis(2-ethylhexyl) sodium sulfosuccinate (AOT, anionic surfactant) with 0.1 of R-value ([water]/[surfactant]) and 3.0 of G/F-value ([glycerol]/[fatty acid]) for the PLE catalyzed esterification. In the aspect of regio-selectivity, the PLE mainly produced 1-monocaprin without any other products (di- and/or tricaprins of subsequent reactions). Furthermore, the degree of esterification at equilibrium state (after 4 h from the initiation) was 62.7% under the optimum conditions at pH 7.0 and 60 degrees C. Based on Hanes-Woolf plot, the apparent Km and Vmax values were calculated to be 16.44 mM and 38.91 MUM/min/mg protein, respectively. PMID- 26672449 TI - AcsA-AcsB: The core of the cellulose synthase complex from Gluconacetobacter hansenii ATCC23769. AB - The gram-negative bacterium, Gluconacetobacter hansenii, produces cellulose of exceptionally high crystallinity in comparison to the cellulose of higher plants. This bacterial cellulose is synthesized and extruded into the extracellular medium by the cellulose synthase complex (CSC). The catalytic component of this complex is encoded by the gene AcsAB. However, several other genes are known to encode proteins critical to cellulose synthesis and are likely components of the bacterial CSC. We have purified an active heterodimer AcsA-AcsB from G. hansenii ATCC23769 to homogeneity by two different methods. With the purified protein, we have determined how it is post-translationally processed, forming the active heterodimer AcsA-AcsB. Additionally, we have performed steady-state kinetic studies on the AcsA-AcsB complex. Finally through mutagenesis studies, we have explored the roles of the postulated CSC proteins AcsC, AcsD, and CcpAx. PMID- 26672450 TI - Discovery and characterization of new O-methyltransferase from the genome of the lignin-degrading fungus Phanerochaete chrysosporium for enhanced lignin degradation. AB - Using bioinformatic homology search tools, this study utilized sequence phylogeny, gene organization and conserved motifs to identify members of the family of O-methyltransferases from lignin-degrading fungus Phanerochaete chrysosporium. The heterologous expression and characterization of O methyltransferases from P. chrysosporium were studied. The expressed protein utilized S-(5'-adenosyl)-L-methionine p-toluenesulfonate salt (SAM) and methylated various free-hydroxyl phenolic compounds at both meta and para site. In the same motif, O-methyltransferases were also identified in other white-rot fungi including Bjerkandera adusta, Ceriporiopsis (Gelatoporia) subvermispora B, and Trametes versicolor. As free-hydroxyl phenolic compounds have been known as inhibitors for lignin peroxidase, the presence of O-methyltransferases in white rot fungi suggested their biological functions in accelerating lignin degradation in white-rot basidiomycetes by converting those inhibitory groups into non-toxic methylated phenolic ones. PMID- 26672451 TI - 2,4-Dichlorophenol hydroxylase for chlorophenol removal: Substrate specificity and catalytic activity. AB - Chlorophenols (CPs) are common environmental pollutants. As such, different treatments have been assessed to facilitate their removal. In this study, 2,4 dichlorophenol (2,4-DCP) hydroxylase was used to systematically investigate the activity and removal ability of 19CP congeners at 25 and 0 degrees C. Results demonstrated that 2,4-DCP hydroxylase exhibited a broad substrate specificity to CPs. The activities of 2,4-DCP hydroxylase against specific CP congeners, including 3-CP, 2,3,6-trichlorophenol, 2-CP, and 2,3-DCP, were higher than those against 2,4-DCP, which is the preferred substrate of previously reported 2,4-DCP hydroxylase. To verify whether cofactors are necessary to promote hydroxylase activity against CP congeners, we added FAD and found that the added FAD induced a 1.33-fold to 5.13-fold significant increase in hydroxylase activity against different CP congeners. The metabolic pathways of the CP degradation in the enzymatic hydroxylation step were preliminarily proposed on the basis of the analyses of the enzymatic activities against 19CP congeners. We found that the high activity and removal rate of 2,4-DCP hydroxylase against CPs at 0 degrees C enhance the low-temperature-adaptability of this enzyme to the CP congeners; as such, the proposed removal process may be applied to biochemical, bioremediation, and industrial processes, particularly in cold environments. PMID- 26672452 TI - Lipase-catalyzed synthesis of palmitanilide: Kinetic model and antimicrobial activity study. AB - Enzymatic syntheses of fatty acid anilides are important owing to their wide range of industrial applications in detergents, shampoo, cosmetics, and surfactant formulations. The amidation reaction of Mucor miehei lipase Lipozyme IM20 was investigated for direct amidation of triacylglycerol in organic solvents. The process parameters (reaction temperature, substrate molar ratio, enzyme amount) were optimized to achieve the highest yield of anilide. The maximum yield of palmitanilide (88.9%) was achieved after 24 h of reaction at 40 degrees C at an enzyme concentration of 1.4% (70 mg). Kinetics of lipase catalyzed amidation of aniline with tripalmitin has been investigated. The reaction rate could be described in terms of the Michaelis-Menten equation with a Ping-Pong Bi-Bi mechanism and competitive inhibition by both the substrates. The kinetic constants were estimated by using non-linear regression method using enzyme kinetic modules. The enzyme operational stability study showed that Lipozyme IM20 retained 38.1% of the initial activity for the synthesis of palmitanilide (even after repeated use for 48 h). Palmitanilide, a fatty acid amide, exhibited potent antimicrobial activity toward Bacillus cereus. PMID- 26672453 TI - A high performance Trichoderma reesei strain that reveals the importance of xylanase III in cellulosic biomass conversion. AB - The ability of the Trichoderma reesei X3AB1strain enzyme preparations to convert cellulosic biomass into fermentable sugars is enhanced by the replacement of xyn3 by Aspergillus aculeatus beta-glucosidase 1 gene (aabg1), as shown in our previous study. However, subsequent experiments using T. reesei extracts supplemented with the glycoside hydrolase (GH) family 10 xylanase III (XYN III) and GH Family 11 XYN II showed increased conversion of alkaline treated cellulosic biomass, which is rich in xylan, underscoring the importance of XYN III. To attain optimal saccharifying potential in T. reesei, we constructed two new strains, C1AB1 and E1AB1, in which aabg1 was expressed heterologously by means of the cbh1 or egl1 promoters, respectively, so that the endogenous XYN III synthesis remained intact. Due to the presence of wild-type xyn3 in T. reesei E1AB1, enzymes prepared from this strain were 20-30% more effective in the saccharification of alkaline-pretreated rice straw than enzyme extracts from X3AB1, and also outperformed recent commercial cellulase preparations. Our results demonstrate the importance of XYN III in the conversion of alkaline pretreated cellulosic biomass by T. reesei. PMID- 26672454 TI - Site-specific integration and constitutive expression of key genes into Escherichia coli chromosome increases shikimic acid yields. AB - As the key starting material for the chemical synthesis of Oseltamivir, shikimic acid (SA) has captured worldwide attention. Many researchers have tried to improve SA production by metabolic engineering, yet expression plasmids were used generally. In recent years, site-specific integration of key genes into chromosome to increase the yield of metabolites showed considerable advantages. The genes could maintain stably and express constitutively without induction. Herein, crucial genes aroG, aroB, tktA, aroE (encoding 3-deoxy-D arabinoheptulosonate-7-phosphate synthase, dehydroquinate synthase, transketolase and shikimate dehydrogenase, respectively) of SA pathway and glk, galP (encoding glucokinase and galactose permease) were integrated into the locus of ptsHIcrr (phosphoenolpyruvate: carbohydrate phosphotransferase system operon) in a shikimate kinase genetic defect strain Escherichia coli BW25113 (DeltaaroL/aroK, DE3). Furthermore, another key gene ppsA (encoding phosphoenolpyruvate synthase) was integrated into tyrR (encoding Tyr regulator protein). As a result, SA production of the recombinant (SA5/pGBAE) reached to 4.14 g/L in shake flask and 27.41 g/L in a 5-L bioreactor. These data suggested that integration of key genes increased SA yields effectively. This strategy is environmentally friendly for no antibiotic is added, simple to handle without induction, and suitable for industrial production. PMID- 26672455 TI - Linker engineering for fusion protein construction: Improvement and characterization of a GLP-1 fusion protein. AB - Protein engineering has been successfully applied in protein drug discovery. Using this technology, we previously have constructed a fusion protein by linking the globular domain of adiponectin to the C-terminus of a glucagon-like peptide-1 (GLP-1) analog. Herein, to further improve its bioactivity, we reconstructed this fusion protein by introducing linker peptides of different length and flexibility. The reconstructed fusion proteins were overexpressed in Escherichia coli and purified using nickel affinity chromatography. Their agonist activity towards receptors of GLP-1 and adiponectin were assessed in vitro by using luciferase assay and AMP-activated protein kinase (AMPK) immunoblotting, respectively. The effects of the selected fusion protein on glucose and lipid metabolism were evaluated in mice. The fusion protein reconstructed using a linker peptide of AMGPSSGAPGGGGS showed high potency in activating GLP-1 receptor and triggering AMPK phosphorylation via activating the adiponectin receptor. Remarkably, the optimized fusion protein was highly effective in lowering blood glucose and lipids in mice. Collectively, these findings demonstrate that the bioactivity of this GLP-1 fusion protein can be significantly promoted by linker engineering, and indicate that the optimized GLP-1 fusion protein is a promising lead structure for anti-diabetic drug discovery. PMID- 26672456 TI - Interaction of small molecules with fungal laccase: A Surface Plasmon Resonance based study. AB - Laccases have a great potential for use in industrial and biotechnological applications. It has affinity towards phenolics and finds major applications in the field of bioremediation. Here, Surface Plasmon Resonance (SPR) as a biosensor with immobilized laccase on chip surface has been studied. Laccase was immobilized by thiol coupling method and compounds containing increasing number of hydroxyl groups were analyzed for their binding affinity at various concentrations in millimolar range. The small molecules like phloroglucinol (1.532*10(-8) M), crocin (3.204*10(-3) M), ascorbic acid (8.331*10(-8) M), kojic acid (6.411*10(-7) M) and saffron (3.466*10(-7) M) were studied and respective KD values are obtained. The results were also confirmed by inhibition assay and IC50 values were calculated. All these molecules showed different affinity towards laccase in terms of KD values. This method may be useful for preliminary screening and characterization of small molecules as laccase substrates, inhibitors or modulators of activity. This method will be useful for rapid screening of phenolics in waste water because of high sensitivity. PMID- 26672457 TI - Overexpression of Candida rugosa lipase Lip1 via combined strategies in Pichia pastoris. AB - In this study, combined strategies were employed to heterologously overexpress Candida rugosa lipase Lip1 (CRL1) in a Pichia pastoris system. The LIP1 gene was systematically codon-optimized and synthesized in vitro. The Lip1 activity of a recombinant strain harboring three copies of the codon-optimized LIP1 gene reached 1200 U/mL in a shake flask culture. Higher lipase activity, 1450 U/mL, was obtained using a five copy number construct. Co-expressing one copy of the ERO1p and BiP chaperones with Lip1p, the CRL1 lipase yield further reached 1758 U/mL, which was significantly higher than that achieved by expressing Lip1p alone or only co-expressing one molecular chaperone. When cultivated in a 3 L fermenter under optimal conditions, the recombinant strain GS115/87-ZA-ERO1p-BiP #7, expressing the molecular chaperones Ero1p and BiP, produced 13,490 U/mL of lipase activity at 130 h, which was greater than the 11,400 U/mL of activity for the recombinant strain GS115/pAO815-alpha-mCRL1 #87, which did not express a molecular chaperone. This study indicates that a strategy of combining codon optimization with co-expression of molecular chaperones has great potential for the industrial-scale production of pure CRL1. PMID- 26672458 TI - Characterization and cloning of laccase gene from Hericium coralloides NBRC 7716 suitable for production of epitheaflagallin 3-O-gallate. AB - Epitheaflagallin 3-O-gallate (ETFGg) is a minor polyphenol found in black tea extract, which has good physiological functions. It is synthesized from epigallocatechin gallate (EGCg) with gallic acid via laccase oxidation. Various basidiomycetes and fungi were screened to find a suitable laccase for the production of ETFGg. A basidiomycete, Hericium coralloides NBRC 7716, produced an appropriate extracellular laccase. The purified laccase produced twice the level of ETFGg compared with commercially available laccase from Trametes sp. The enzyme, termed Lcc2, is a monomeric protein with an apparent molecular mass of 67.2 kDa. The N-terminal amino acid sequence of Lcc2 is quite different from laccase isolated from the fruiting bodies of Hericium. Lcc2 showed similar substrate specificity to known laccases and could oxidize various phenolic substrates, including pyrogallol, gallic acid, and 2,6-dimethoxyphenol. The full length lcc2 gene was obtained by PCR using degenerate primers, which were designed based on the N-terminal amino acid sequence of Lcc2 and conserved copper binding sites of laccases, and 5'-, and 3'-RACE PCR with mRNA. The Lcc2 gene showed homology with Lentinula edodes laccase (sharing 77% amino acid identity with Lcc6). We successfully produced extracellular Lcc2 using a heterologous expression system with Saccharomyces cerevisiae. Moreover, it was confirmed that the recombinant laccase generates similar levels of ETFGg as the native enzyme. PMID- 26672459 TI - Effect of spermidine and its metabolites on the activity of pea seedlings diamine oxidase and the problems of biosensing of biogenic amines with this enzyme. AB - Spermidine is one of the several biogenic amines, produced during the microbial decarboxylation of proteins. Individual biogenic amines in the formed mixtures are frequently analyzed with oxygen sensor based biosensors, as their content serves as a good biomarker for the determination of food quality. In these biosensors, diamine oxidase from pea seedlings (PSAO), catalyzing the oxidation of various biogenic amines by dissolved oxygen is commonly used for the bio recognition of amines. However, in the presence of spermidine and/or its metabolite 1,3-diaminopropane, the activity of PSAO and the sensitivity of PSAO based biosensors decrease due to inhibition. The inhibition constant of soluble spermidine, acting as an inhibiting substrate toward PSAO, was found to be (40+/ 15) mM in freshly prepared solution and (0.28+/-0.05) mM in solution, incubated 30 days at room temperature. The inhibition constant of 1,3-diaminopropane, acting as a competitive inhibitor, was (0.43+/-0.12) mM as determined through the oxidation reaction of cadaverine. The metabolic half-life of soluble spermidine was 7 days at room temperature and 186 days at 4 degrees C. The kinetic measurements were carried out with an oxygen sensor; the composition of the solution of degraded spermidine was analyzed with MS. PMID- 26672460 TI - Covalent immobilization of a flavoprotein monooxygenase via its flavin cofactor. AB - A generic approach for flavoenzyme immobilization was developed in which the flavin cofactor is used for anchoring enzymes onto the carrier. It exploits the tight binding of flavin cofactors to their target apo proteins. The method was tested for phenylacetone monooxygenase (PAMO) which is a well-studied and industrially interesting biocatalyst. Also a fusion protein was tested: PAMO fused to phosphite dehydrogenase (PTDH-PAMO). The employed flavin cofactor derivative, N6-(6-carboxyhexyl)-FAD succinimidylester (FAD*), was covalently anchored to agarose beads and served for apo enzyme immobilization by their reconstitution into holo enzymes. The thus immobilized enzymes retained their activity and remained active after several rounds of catalysis. For both tested enzymes, the generated agarose beads contained 3 U per g of dry resin. Notably, FAD-immobilized PAMO was found to be more thermostable (40% activity after 1 h at 60 degrees C) when compared to PAMO in solution (no activity detected after 1 h at 60 degrees C). The FAD-decorated agarose material could be easily recycled allowing multiple rounds of immobilization. This method allows an efficient and selective immobilization of flavoproteins via the FAD flavin cofactor onto a recyclable carrier. PMID- 26672461 TI - Influence of immobilization strategies on biosensing response characteristics: A comparative study. AB - The immobilization technique plays an important role in fabrication of a biosensor. NiO based cholesterol biosensor has been used to study the effect of various immobilization techniques on the biosensing response characteristics. The biosensors were fabricated by immobilizing cholesterol oxidase on NiO thin films by three different immobilization techniques viz. physisorption, cross-linking and covalent binding. The study reveals a strong dependence of biosensing response on corresponding immobilization technique. The biosensor based on immobilization by covalent bonding shows superior response characteristics as compared to others owing to its zero length. The results highlight the significance of immobilization technique for biosensor fabrication. PMID- 26672462 TI - L-Arginine oxidase from Pseudomonas sp. TPU 7192: Characterization, gene cloning, heterologous expression, and application to L-arginine determination. AB - L-Arginine oxidase (AROD, EC 1.4.3.-) was discovered in newly discovered Pseudomonas sp. TPU 7192 and its characteristics were described. The molecular mass (MS) of the enzyme was estimated to be 528 kDa, which was accounted for by eight identical subunits with MS of 66 kDa each. AROD was identified as a flavin adenine dinucleotide (FAD)-dependent enzyme with 1 mol of FAD being contained in each subunit. It catalyzed the oxidative deamination of L-arginine and converted L-arginine to 2-ketoarginine, which was non-enzymatically converted into 4 guanidinobutyric acid when the hydrogen peroxide (H2O2) formed by L-arginine oxidation was not removed. In contrast, 2-ketoarginine was present when H2O2was decomposed. AROD was specific to L-arginine with a Km value of 149 MUM. It exhibited maximal activity at 55 degrees C and pH 5.5. AROD was stable in the pH range 5.5-7.5 and >95% of its original activity was below 60 degrees C at pH 7.0. Since these enzymatic properties are considered suitable for the determination of L-arginine, the gene was cloned and expressed in a heterologous expression system. We herein successfully developed a new simple enzymatic method for the determination of L-arginine using Pseudomonas AROD. PMID- 26672463 TI - Isolation and divalent-metal activation of a beta-xylosidase, RUM630-BX. AB - The gene encoding RUM630-BX, a beta-xylosidase/arabinofuranosidase, was identified from activity-based screening of a cow rumen metagenomic library. The recombinant enzyme is activated as much as 14-fold (kcat) by divalent metals Mg(2+), Mn(2+) and Co(2+) but not by Ca(2+), Ni(2+), and Zn(2+). Activation of RUM630-BX by Mg(2+) (t0.5 144 s) is slowed two-fold by prior incubation with substrate, consistent with the X-ray structure of closely related xylosidase RS223-BX that shows the divalent-metal activator is at the back of the active site pocket so that bound substrate could block its entrance. The enzyme is considerably more active on natural substrates than artificial substrates, with activity (kcat/Km) of 299 s(-1) mM(-1) on xylotetraose being the highest reported. PMID- 26672464 TI - Study of microwave effects on the lipase-catalyzed hydrolysis. AB - The effect of microwave heating on lipase-catalyzed reaction remains controversial. It is not clear whether the reaction rate enhancements are purely due to thermal/heating effects or to non-thermal effects. Therefore, quantitative mass spectrometry was used to conduct accurate kinetic analysis of lipase catalyzed hydrolysis of triolein by microwave and conventional heating. Commercial lipases from Candida rugosa (CRL), Porcine Pancreas (PPL), and Burkholderia cepacia (BCL) were used. Hydrolysis reactions were performed at various temperatures and pH levels, along with various amounts of buffer and enzymes. Hydrolysis product yields at each time point using an internal-standard method showed no significant difference between microwave and conventional heating conditions when the reaction was carried out at the same temperature. CRL showed optimum catalytic activity at 37 degrees C, while PPL and BCL had better activities at 50 degrees C. The phosphate buffer was found to give a better hydrolysis yield than the Tris-HCl buffer. Overall results prove that a non thermal effect does not exist in microwave-assisted lipase hydrolysis of triolein. Therefore, conventional heating at high temperatures (e.g., 50 degrees C) can be also used to accelerate hydrolysis reactions. PMID- 26672465 TI - Lipase in biphasic alginate beads as a biocatalyst for esterification of butyric acid and butanol in aqueous media. AB - Esterification of organic acids and alcohols in aqueous media is very inefficient due to thermodynamic constraints. However, fermentation processes used to produce organic acids and alcohols are often conducted in aqueous media. To produce esters in aqueous media, biphasic alginate beads with immobilized lipase are developed for in situ esterification of butanol and butyric acid. The biphasic beads contain a solid matrix of calcium alginate and hexadecane together with 5 mg/mL of lipase as the biocatalyst. Hexadecane in the biphasic beads serves as an organic phase to facilitate the esterification reaction. Under optimized conditions, the beads are able to catalyze the production of 0.16 mmol of butyl butyrate from 0.5 mmol of butyric acid and 1.5 mmol of butanol. In contrast, when monophasic beads (without hexadecane) are used, only trace amount of butyl butyrate is produced. One main application of biphasic beads is in simultaneous fermentation and esterification (SFE) because the organic phase inside the beads is very stable and does not leach out into the culture medium. SFE is successfully conducted with an esterification yield of 6.32% using biphasic beads containing iso-octane even though the solvent is proven toxic to the butanol producing Clostridium spp. PMID- 26672466 TI - Characterization of a novel esterase Rv1497 of Mycobacterium tuberculosisH37Rv demonstrating beta-lactamase activity. AB - The Rv1497 (LipL) of the Mycobacterium tuberculosis H37Rv was predicted to be similar to hypothetical esterases and penicillin binding proteins ofM. tuberculosis as well as to be involved in lipid metabolism. Sequence alignment revealed that Rv1497 protein contains characteristic consensus beta-lactamase motif 'SXXK' in addition to a conserve pentapeptide -GXSXG-, characteristic of lipolytic enzymes, at the C-terminus of protein in contrast to its usual N terminus location. For detailed characterization of protein, the rv1497 gene was cloned, expressed with N-terminal His-tag and purified to homogeneity on Ni-NTA column. Rv1497 demonstrated both esterase and beta-lactamase activities. A serine located within consensus beta-lactamase motif 'SXXK' was identified as catalytic residue in both esterase and beta-lactamase enzymatic activities whereas serine residue located within conserved pentapeptide did not show any effect on both enzyme activities. The catalytic residues of Rv1497 for beta-lactamase activity were determined to be Ser88, Tyr-175 and His355 residues by site-directed mutagenesis. The enzyme demonstrated preference for short chain esters (pNP butyrate). The expression of lipL gene was significantly up-regulated during acidic stress as compared to normal conditions in in vitro culture of M. tuberculosis H37Ra. This is perhaps the first report demonstrating an esterase of mycobacterium showing beta-lactamase activity. PMID- 26672467 TI - Highly effective detection of inflamed cells using a modified bradykinin ligand labeled with FITC fluorescence. AB - Detection of inflammation in live cells is important because long-lasting inflammation is considered to be a primary cause of several diseases. However, few reports have been published on imaging analysis of inflammation in live cells. In this study, we developed an effective imaging system for detection of inflamed cells using a bradykinin ligand (BK) or a modified BK (mBK), which has specific affinity with the cellular B1R receptor. Synthetic BK or mBK labeled with FITC at the N-terminus was employed for discriminating between inflamed and normal cells; this method was found to be effective for detection of inflammation in live cells. In addition, using the mBK-based cell imaging system, we successfully performed flow-based analysis of live cell inflammation on a micro chip channel, composed of a Starna flow cell and PDMS (Polydimethylsiloxane) walls. The BK-based cell imaging methods designed here would be a useful platform for development of a high-throughput live cell analysis system for investigating the factors underlying inflammation or for screening of anti-inflammation candidate drugs. PMID- 26672468 TI - Improved PCR performance and fidelity of double mutant Neq A523R/N540R DNA polymerase. AB - We previously reported that Neq A523R DNA polymerase is more efficient in PCR than wild-type Neq DNA polymerase, and amplifies products more rapidly. Neq A523R DNA polymerase also amplifies templates more rapidly than Pfu DNA polymerase, but has a lower fidelity than Pfu DNA polymerase. To improve product yield and the fidelity of amplification simultaneously, we constructed and characterized the double mutant Neq A523R/N540R. The yield of PCR products was greater for Neq A523R/N540R DNA polymerase than wild-type and other mutant DNA polymerases, and the Neq double mutant catalyzed amplification of a 12-kb PCR product from a lambda template with an extension time of 3 min. The PCR error rate of Neq A523R/N540R DNA polymerase (6.3*10(-5)) was roughly similar to that of Pfu DNA polymerase (4.8*10(-5)), but much lower than those of wild-type Neq DNA polymerase (57.2*10(-5)), Neq A523R DNA polymerase (13.1*10(-5)), and Neq N540R DNA polymerase (37.7*10(-5)). These results indicated that A523R and N540R mutations of Neq DNA polymerase had synergistic effects on its fidelity. PMID- 26672469 TI - Prevalence of Mobile Phone Dependence in Secondary School Adolescents. AB - INTRODUCTION: Mobile phones have become an essential part of modern human life. They have many attributes which makes them very attractive to both young and old. There has been an increasing trend of use of mobile phones among students. Data has now started emerging with respect to the negative physical and psychological consequences of excessive use of mobile phones. New research has shown excessive use of mobile phones leading to development of symptoms suggestive of dependence syndrome. AIM: To study the prevalence of Mobile Phone Dependence (MPD) in secondary school adolescents. SETTING AND DESIGN: Cross-sectional, observational study conducted in secondary section of English-medium schools at Navi Mumbai (India). MATERIALS AND METHODS: Four hundred and fifteen students studying in 8(th), 9(th) and 10(th) standards of schools at Navi Mumbai (India) having personal mobile phone were randomly included in the study. Participant information like age, gender, family type, phone type, duration of use per day and years of mobile phone usage was recorded. They were administered an MPD questionnaire based upon the dependence syndrome criteria as per ICD-10. According to their responses, participants who fulfilled three or more of the diagnostic criteria were rated as having MPD. RESULTS: Mobile Phone Dependence was found in 31.33% of sample students. It was significantly associated with gender (p=0.003, OR=1.91, CI: 1.23-2.99), family type (p=0.0012), type of mobile phone used (p<0.001, OR=2.6, CI: 1.63-4.35), average time per day spent using mobile phone (p<0.001) and years of mobile phone usage (p =0.004, OR=2.4, CI: 1.31-4.55). CONCLUSION: Mobile Phone Dependence has been found to be an emerging public health problem. There is need to recognize and identify early the growing trends and negative consequences of inappropriate mobile phone use in young users so as to generate awareness, and plan educational and treatment interventions, if need be, so as to prevent a major public health concern. PMID- 26672470 TI - Quantitative proteomics reveals novel therapeutic and diagnostic markers in hypertension. AB - Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension. PMID- 26672471 TI - The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part II: Examples of labral pathologies. AB - Labral pathologies of the glenohumeral joint are most commonly caused by trauma. The majority of lesions affect the anterior part of labrum, resulting from much higher frequency of anterior shoulder dislocations over posterior ones. Another subgroup of labral lesions, not directly related to joint instability, are SLAP tears. Other findings include degenerative changes of labrum and paralabral cysts. Diagnostic imaging is crucial for making a decision regarding operative treatment. Apart from a standard X-ray examination, the imaging mainly relies on magnetic resonance or computed tomography arthrography. Based on their own experience, the authors propose the use of ultrasound in the assessment of labral tears of the glenohumeral joint. Different signs indicating labral pathology may be discovered and assessed during ultrasound examination. They include permanent displacement of the labrum onto the glenoid, labral instability during dynamic examination, lack of the labrum in the anatomical position, hypoechoic zone at the base of the labrum >2 mm in width, residual or swollen labrum as well as paralabral cyst(s). The most frequent appearance of labral pathology is displacement of the anteroinferior labrum onto the external aspect of the glenoid typically seen after anterior shoulder dislocation. The another most important US feature is labral instability while dynamically examined. The swelling or reduced size of the labrum usually indicates degeneration. This article presents sonographic images of selected labral pathologies. PMID- 26672472 TI - Systemic Infection of Maize, Sorghum, Rice, and Beet Seedlings with Fumonisin Producing and Nonproducing Fusarium verticillioides Strains. AB - Two fumonisin-nonproducing strains of Fusarium verticillioides and their fumonisin producing progenitors were tested for aggressiveness toward maize, sorghum, rice, and beetroot seedlings grown under greenhouse conditions. None of the plants showed obvious disease symptoms after root dip inoculation. Fungal biomass was determined by species-specific real-time PCR. No significant (P = 0.05) differences in systemic colonization were detected between the wild type strains and mutants not producing fumonisins. F. verticillioides was not detected in any of the non-inoculated control plants. The fungus grew from roots to the first two internodes/leaves of maize, rice and beet regardless of fumonisin production. The systemic growth of F. verticillioides in sorghum was limited. The results showed that fumonisin production was not required for the infection of roots of maize, rice and beet by F. verticillioides. PMID- 26672473 TI - Atypical Pneumonia - Screening in a Tertiary Care Centre. AB - INTRODUCTION: Pneumonia is one of the leading infectious causes of mortality and morbidity worldwide. Atypical respiratory pathogens account for 30 - 40% of these infections. The three most important atypical pathogens are Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila. AIM: To screen for atypical pathogens as cause for community acquired pneumonia. MATERIALS AND METHODS: A cross-sectional study was done with 107 patients who had clinical suspicion of atypical pneumonia. The presence of atypical pathogens Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila were screened from the patient's sample. Respiratory samples in the form of sputum, Broncheoalveolar lavage and Non- Broncheoalveolar lavage were used for cultivation of Mycoplasma pneumoniae and Legionella pneumophila. Urine specimen was used for the detection of Legionella antigen. Serum samples were used for the detection of Mycoplasma pneumoniae IgM and Chlamydophila pneumoniae IgM antibodies. RESULTS: Among the 107 samples screened, 13(12.1%) were positive for antibodies against atypical pathogens. Out of which 7(6.5%) had IgM antibodies against Mycoplasma pneumoniae and the rest 6(5.6%) had Chlamydophila pneumoniae IgM antibodies. All the samples were culture negative for Mycoplasma pneumoniae and Legionella pneumophila. Urinary antigen detection for Legionella pneumophila was also negative in patients. CONCLUSION: Atypical pathogens should also be considered routinely as a cause of lower respiratory tract infections, especially Chlamydia pneumoniae and Mycoplasma pneumoniae in our country. Serological diagnosis by ELISA can be adopted for determining the infections by atypical pathogens as cultivation is difficult and also requires special media and prolonged incubation. This may not be feasible for many laboratories. Early diagnosis and treatment will reduce the complications. PMID- 26672474 TI - Impacts of Long-Term Obesity on the Health Status of Samoan and Tongan Men in the United States: Results from the Pacific Islander Health Study. AB - OBJECTIVE: To examine the impacts of long-standing obesity (BMIs >= 30.0 kg/m(2)) on health outcomes among Samoan and Tongan men (aged >= 18 years) in California using a life course perspective. DESIGN: Cross-sectional analysis of 103 males from the Pacific Islander Health Study (PIHS), a probability sample modeled after the National Health Interview Survey (NHIS). SETTING: Urban residential neighborhoods in San Mateo and Los Angeles counties using a multistage, cluster sample design. MAIN OUTCOME MEASURES: BMI, diabetes, hypertension, total cholesterol, smoking, drinking, arthritis, gout and migraines. RESULTS: Bivariate analysis shows high rates of poor health outcomes distributed throughout the obese and non-obese sample. Logistic analysis finds that being obese does not significantly increase observed negative health outcomes. After controlling for socio-demographic characteristics, the presence of obesity results in non significant findings for hypertension (OR=1.02; CI: .21, 4.91), and high cholesterol (OR=.52; CI: .10, 2.73), while obesity significantly reduces the risk of diabetes by 60% (OR=.40; CI: .14, 1.17). When applying disease counts, obese men have a significantly lower risk of reporting multiple health conditions (OR=.72; CI: .52, 1.00). CONCLUSION: Overall, the health of Samoan and Tongan males in California is uniformly poor and obesity alone does not significantly increase risks of poor health outcomes. Using a life course perspective, the analysis offers new insights on the basic health of this understudied population. PMID- 26672475 TI - The predictive role of circulating microparticles in patients with chronic heart failure. AB - AIM: The study aim was to evaluate whether circulating microparticles with apoptotic or non-apoptotic phenotypes are useful for risk assessment of 3-year cumulative fatal and non-fatal cardiovascular events in CHF patients. METHODS: The incidence of fatal and non-fatal cardiovascular events, as well as the frequency of occurrence of death from any cause in a cohort of 388 patients with CHF during 3 years of observation was studied prospectively. Circulating levels of NT-pro brain natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and endothelial apoptotic microparticles (EMPs) were measured at baseline. RESULTS: Median follow-up was 2.32 years (IQR = 1.8-3.1). During follow-up, 110 cardiovascular events (including 43 fatal cases) were determined. Additionally, 74 subjects were hospitalized repetitively due to worsening CHF and also 16 subjects were readmitted in the hospital due to other cardiovascular reasons. In the univariate logistic regression analysis, the main factors independently related with cumulative endpoints were creatinine, fasting glucose, HbA1c, total cholesterol, uric acid, various types of EPMs, NT-pro-BNP, hs-CRP, NYHA class, decreased left ventricular ejection fraction (LVEF) less 45%, and type 2 diabetes mellitus. In multivariate model NYHA class, decreased LVEF (less 45%), NT-pro-BNP, hs-CRP, CD144 +/CD31 +/annexin V + EMPs, and CD31 +/annexin V + EMPs remained statistically significant for cumulative endpoint. Adding of CD144 +/CD31 +/annexin V + EMCs and CD31 +/annexin V + EMCs to the standard ABC model may improve the relative IDI for cumulative endpoint by 11.4% and 10.5% respectively. CONCLUSION: Apoptotic phenotype of circulating microparticles may relate 3-year combined clinical outcomes in CHF patients. PMID- 26672477 TI - Pancreatic Cancer: Progress in Systemic Therapy. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer related deaths in the Western world. Due to lack of specific symptoms and no accessible precursor lesions, primary diagnosis is commonly delayed, resulting in the identification of only 15-20% of patients with potentially curable disease. The major limiting factor is an already locally advanced or metastatic disease at the time of diagnosis. Consequently, systemic therapy forms the backbone of treatment strategy for the majority of patients. SUMMARY: A deeper understanding of the molecular characteristics of pancreatic cancer has led to the identification of several potential therapeutic targets. A variety of targeted therapies are currently under clinical evaluation as single agents or in combination with chemotherapy for PDAC. This review highlights the current state of chemotherapy in pancreatic cancer and provides an outlook on its future perspectives. KEY MESSAGE: This review focuses on the current chemotherapy regimens for the systemic treatment of PDAC. PRACTICAL IMPLICATIONS: Various neoadjuvant approaches have been explored, including chemoradiation, chemotherapy followed by chemoradiation or intensified chemotherapy without defining a standard of care so far. The standard of care is gemcitabine or 5-fluorouracil. The oral fluoropyrimidine S-1 may be a promising new agent in this setting. For first-line treatment of metastatic pancreatic cancer, no targeted therapy has yet demonstrated clinical benefit apart from the combination of the tyrosine kinase inhibitor erlotinib plus gemcitabine. Recently, novel chemotherapeutic regimens such as FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound paclitaxel have been introduced. Both combinations have proved to be superior to the standard gemcitabine regimen. For second-line treatment the combination of 5 fluorouracil/leucovorin and oxaliplatin yields improved results compared to best supportive care. PMID- 26672476 TI - HIGH REPETITION JUMP TRAINING COUPLED WITH BODY WEIGHT SUPPORT IN A PATIENT WITH KNEE PAIN AND PRIOR HISTORY OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A CASE REPORT. AB - BACKGROUND AND PURPOSE: Patients frequently experience long-term deficits in functional activity following anterior cruciate ligament reconstruction, and commonly present with decreased confidence and poor weight acceptance in the surgical knee. Adaptation of neuromuscular behaviors may be possible through plyometric training. Body weight support decreases intensity of landing sufficiently to allow increased training repetition. The purpose of this case report is to report the outcomes of a subject with a previous history of anterior cruciate ligament (ACL) reconstruction treated with high repetition jump training coupled with body weight support (BWS) as a primary intervention strategy. CASE DESCRIPTION: A 23-year old female, who had right ACL reconstruction seven years prior, presented with anterior knee pain and effusion following initiation of a running program. Following visual assessment of poor mechanics in single leg closed chain activities, landing mechanics were assessed using 3-D motion analysis of single leg landing off a 20 cm box. She then participated in an eight week plyometric training program using a custom-designed body weight support system. The International Knee Documentation Committee Subjective Knee Form (IKDC) and the ACL-Return to Sport Index (ACL-RSI) were administered at the start and end of treatment as well as at follow-up testing. OUTCOMES: The subject's IKDC and ACL-RSI scores increased with training from 68% and 43% to 90% and 84%, respectively, and were retained at follow-up testing. Peak knee and hip flexion angles during landing increased from 47 degrees and 53 degrees to 72 degrees and 80 degrees respectively. Vertical ground reaction forces in landing decreased with training from 3.8 N/kg to 3.2 N/kg. All changes were retained two months following completion of training. DISCUSSION: The subject experienced meaningful changes in overall function. Retention of mechanical changes suggests that her new landing strategy had become a habitual pattern. Success with high volume plyometric training is possible when using BWS. Clinical investigation into the efficacy of body weight support as a training mechanism is needed. LEVEL OF EVIDENCE: Level 4 - Case Report. PMID- 26672478 TI - In silico characterisation, homology modelling and structure-based functional annotation of blunt snout bream (Megalobrama amblycephala) Hsp70 and Hsc70 proteins. AB - BACKGROUND: Heat shock proteins play an important role in protection from stress stimuli and metabolic insults in almost all organisms. METHODS: In this study, computational tools were used to deeply analyse the physicochemical characteristics and, using homology modelling, reliably predict the tertiary structure of the blunt snout bream (Ma-) Hsp70 and Hsc70 proteins. Derived three dimensional models were then used to predict the function of the proteins. RESULTS: Previously published predictions regarding the protein length, molecular weight, theoretical isoelectric point and total number of positive and negative residues were corroborated. Among the new findings are: the extinction coefficient (33725/33350 and 35090/34840 - Ma-Hsp70/ Ma-Hsc70, respectively), instability index (33.68/35.56 - both stable), aliphatic index (83.44/80.23 - both very stable), half-life estimates (both relatively stable), grand average of hydropathicity (-0.431/-0.473 - both hydrophilic) and amino acid composition (alanine-lysine-glycine/glycine-lysine-aspartic acid were the most abundant, no disulphide bonds, the N-terminal of both proteins was methionine). Homology modelling was performed by SWISS-MODEL program and the proposed model was evaluated as highly reliable based on PROCHECK's Ramachandran plot, ERRAT, PROVE, Verify 3D, ProQ and ProSA analyses. CONCLUSIONS: The research revealed a high structural similarity to Hsp70 and Hsc70 proteins from several taxonomically distant animal species, corroborating a remarkably high level of evolutionary conservation among the members of this protein family. Functional annotation based on structural similarity provides a reliable additional indirect evidence for a high level of functional conservation of these two genes/proteins in blunt snout bream, but it is not sensitive enough to functionally distinguish the two isoforms. PMID- 26672479 TI - The Correlation of Tunnel Position, Orientation and Tunnel Enlargement in Outside in Single-Bundle Anterior Cruciate Ligament Reconstruction. AB - PURPOSE: Tunnel widening after anterior cruciate ligament (ACL) reconstruction is a frequently described phenomenon. The possible etiology is multi-factorial with some mechanical and biological factors. Among those, we intended to determine the relation between the location and orientation of the femoral tunnel and the femoral tunnel enlargement after outside-in single-bundle ACL reconstruction. MATERIALS AND METHODS: A retrospective study including 42 patients who received single-bundle ACL reconstruction with the outside-in technique was conducted. Femoral and tibial tunnel locations were evaluated with the quadrant method and bird's-eye view using volume-rendering computed tomography. The angle and diameter of bone tunnel and the degree of tunnel enlargement were evaluated using standard radiographs. RESULTS: The degree of femoral tunnel enlargements were 42% and 36% on the anteroposterior (AP) and lateral radiographs, respectively, and the degree of tibial tunnel enlargements were 22% and 23%, respectively. Shallower location of the femoral tunnel was significantly correlated with greater femoral tunnel enlargement on the AP radiograph (r=0.998, p=0.004) and the lateral radiograph (r=0.72, p=0.005) as was the higher location of the femoral tunnel on the AP radiograph (r=-0.47, p=0.01) and the lateral radiograph (r=-0.36, p=0.009) at 12 months after surgery. CONCLUSIONS: This study revealed that more anterior and higher location and more horizontal orientation of the femoral tunnel in coronal plane could result in widening of the femoral tunnel in outside-in single-bundle ACL reconstruction. PMID- 26672481 TI - Identification of RNA aptamers with riboswitching properties. AB - During the past years customized gene network design has become of tremendous interest among various disciplines in life science. The identification of artificial genetic elements sensitive to internal or external stimuli constitutes the foundation for the design and realization of conditional gene expression systems. Typically, strategies involving selection or screening steps are employed alongside approaches focusing on rational design to select for the desired functionality of a given element. Here we present a fluorescence-based in vivo screening approach that combines an initial in vitro selection with subsequent extensive screening steps and a final rational design to identify RNA based regulators in baker's yeast. These artificial RNA regulators, termed synthetic riboswitches, are derived from RNA aptamers. Our method allows for the separation of aptamers featuring the potential to be transformed into a riboswitch from those inherently unable to confer control over gene expression. The system may be applied to virtually all existing aptamer-ligand pairs and as such presents a powerful means to enhance the setup of switchable genetic circuits. PMID- 26672482 TI - Fully epitaxial C1b-type NiMnSb half-Heusler alloy films for current perpendicular-to-plane giant magnetoresistance devices with a Ag spacer. AB - Remarkable magnetic and spin-dependent transport properties arise from well designed spintronic materials and heterostructures. Half-metallic Heusler alloys with high spin polarization exhibit properties that are particularly advantageous for the development of high-performance spintronic devices. Here, we report fully (001)-epitaxial growth of a high-quality half-metallic NiMnSb half-Heusler alloy films, and their application to current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) devices with Ag spacer layers. Fully (001)-oriented NiMnSb epitaxial films with very flat surface and high magnetization were prepared on Cr/Ag-buffered MgO(001) single crystalline substrates by changing the substrate temperature. Epitaxial CPP-GMR devices using the NiMnSb films and a Ag spacer were fabricated, and room-temperature (RT) CPP-GMR ratios for the C1b-type half-Heusler alloy were determined for the first time. A CPP-GMR ratio of 8% (21%) at RT (4.2 K) was achieved in the fully epitaxial NiMnSb/Ag/NiMnSb structures. Furthermore, negative anisotropic magnetoresistance (AMR) ratio and small discrepancy of the AMR amplitudes between RT and 10 K were observed in a single epitaxial NiMnSb film, indicating robust bulk half metallicity against thermal fluctuation in the half-Heusler compound. The modest CPP-GMR ratios could be attributed to interface effects between NiMnSb and Ag. This work provides a pathway for engineering a new class of ordered alloy materials with particular emphasis on spintronics. PMID- 26672480 TI - Bisphenol A Interaction With Brain Development and Functions. AB - Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose-response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health. PMID- 26672483 TI - Hepatocellular Carcinoma: Current Concepts in Diagnosis, Staging and Treatment. AB - BACKGROUND: Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer related death, with HCC representing more than 90% of primary liver cancers. During the last decade, much progress has been made with respect to the definition of patient populations at risk who may benefit from surveillance strategies, as well as in the diagnosis and treatment of the disease. SUMMARY: New locoregional and systemic therapies have significantly increased the survival of patients with HCC. A multitude of clinical trials addressing patients with HCC have led to advancements in the allocation of subgroups of patients to their optimal individual treatment strategy. This review provides an overview on recent developments in diagnostic and therapeutic modalities and an outlook on future directions in the management of HCC. KEY MESSAGE: New locoregional and systemic therapies in patients with HCC have significantly improved clinical outlook and patient survival. This review provides an overview of recent developments in diagnostics and therapeutics, as well as an outlook on future directions in the management of HCC. PRACTICAL IMPLICATIONS: Transabdominal ultrasound is the method of choice for the surveillance of patients at risk of developing HCC, and any suspicious focal lesion in the liver should be characterized. Contrast enhanced ultrasound with application of second-generation contrast agents enables visualization of tumor vascularity. The Barcelona Clinic Liver Cancer (BCLC) system is the most widely used classification system to guide the clinical management of HCC. Liver resection should be considered for patients with well preserved liver function and without portal hypertension or elevated bilirubin. Patients not suitable for resection should undergo local tumor ablation. Candidates who are eligible for liver transplantation may benefit from bridging therapy during their waiting period. Patients in the BCLC B category benefit from locoregional transarterial therapy; transarterial chemoembolization is the treatment of choice. Sorafenib is the only systemic therapy that has been shown to prolong overall survival in patients with advanced disease, and is therefore recommended in patients with well-preserved liver function. PMID- 26672485 TI - Intracellular delivery of biomineralized monoclonal antibodies to combat viral infection. AB - Conventional therapeutic monoclonal antibodies (mAbs) are invalid for intracellular viruses but by using in situ biomineralization treatment, they can be successfully delivered into cells to inhibit intracellular viral replication. This achievement significantly expands the applications of mAbs and provides a new intracellular strategy to control viral infections. PMID- 26672484 TI - A functional 4-hydroxybenzoate degradation pathway in the phytopathogen Xanthomonas campestris is required for full pathogenicity. AB - Plants contain significant levels of natural phenolic compounds essential for reproduction and growth, as well as defense mechanisms against pathogens. Xanthomonas campestris pv. campestris (Xcc) is the causal agent of crucifers black rot. Here we showed that genes required for the synthesis, utilization, transportation, and degradation of 4-hydroxybenzoate (4-HBA) are present in Xcc. Xcc rapidly degrades 4-HBA, but has no effect on 2-hydroxybenzoate and 3 hydroxybenzoate when grown in XOLN medium. The genes for 4-HBA degradation are organized in a superoperonic cluster. Bioinformatics, biochemical, and genetic data showed that 4-HBA is hydroxylated by 4-HBA 3-hydroxylase (PobA), which is encoded by Xcc0356, to yield PCA. The resulting PCA is further metabolized via the PCA branches of the beta-ketoadipate pathway, including Xcc0364, Xcc0365, and PcaFHGBDCR. Xcc0364 and Xcc0365 encode a new form of beta-ketoadipate succinyl coenzyme A transferase that is required for 4-HBA degradation. pobA expression was induced by 4-HBA via the transcriptional activator, PobR. Radish and cabbage hydrolysates contain 2-HBA, 3-HBA, 4-HBA, and other phenolic compounds. Addition of radish and cabbage hydrolysates to Xcc culture significantly induced the expression of pobA via PobR. The 4-HBA degradation pathway is required for full pathogenicity of Xcc in radish. PMID- 26672486 TI - Hemorrhagic stroke in children caused by Bothrops marajoensis envenoming: a case report. AB - According to the World Health Organization, snakebites are considered neglected diseases. Bothrops, the genus most frequently implicated in envenomations in Brazil, includes the species B. marajoensis Hoge, 1966, part of the complex B. atrox, which is found in the savannas of Marajo Island, Para state, Brazil, a region that presents scarce epidemiological data. This work reports the first case of hemorrhagic stroke in a child, attributed to delayed medical care after snakebite envenoming by Bothrops marajoensis in Anajas city, Marajo Island, Para, Brazil, which led to permanent hemiplegia as a sequela. PMID- 26672487 TI - Acculturation and Insulin Resistance among US Chinese Immigrant Women. AB - OBJECTIVE: Chinese immigrants in the United States undergo a transition to increased chronic disease risk commonly attributed to acculturative changes. Longitudinal data to confirm this are lacking. We examined acculturation in relation to insulin resistance in a sample of Chinese immigrant women to determine differences by level of education and possible mediation by anthropometry and diet. DESIGN: Longitudinal study. SETTING: Philadelphia, Pennsylvania. PARTICIPANTS: 305 Chinese immigrant women recruited October 2005 to April 2008 and followed until April 2010. MAIN OUTCOME MEASURES: Association of acculturation, measured using the General Ethnicity Questionnaire - American version (GEQA), with homeostasis model assessment (HOMA) score as an indicator of insulin resistance, modeled using generalized estimating equations to account for repeated measures over time. RESULTS: GEQA was associated with log HOMA score, but only in women with <9 years of education (beta [SE] = .09 [.04], P=.02; interaction P=.02). The association persisted with adjustment for body mass index, waist circumference, and dietary variables. CONCLUSIONS: These findings provide longitudinal evidence that insulin resistance increases with acculturation. However, the association was apparent only in less-educated immigrants and may be mediated by a pathway other than changes in anthropometry and diet. PMID- 26672489 TI - Bandgap engineering of Fe2O3 with Cr - application to photoelectrochemical oxidation. AB - Hematite is a promising material for photoelectrochemical (PEC) water splitting. While it has a low bandgap of ~2.1 eV it is still larger than the optimal value of ~1.8 eV. Previous work on epitaxial films has shown that Cr-doping leads to a shift of the bandgap as measured optically, but more importantly, also as measured by photoconductivity - to a value as low as 1.6 eV. We extend this work to polycrystalline films and attempt to use Cr-doping to lower the photon energy for which photocurrent can be generated. Our polycrystalline films show strong agreement with epitaxial films with regards to optical measurements of the direct and indirect bandgap. Furthermore, we find that Cr-doped polycrystalline films show photoconductivity at notably lower photon energies than undoped films, consistent with epitaxial results. However, when using Cr-doped films for photoelectrochemistry we find little to no shift of the photocurrent onset. We outline a number of proposals for why this could be the case, with a focus on the possibility of the existence of separate O 2p and Cr 3d states that would impact PEC but not PC behaviour. PMID- 26672488 TI - Enthesopathies and enthesitis. Part 2: Imaging studies. AB - The pathologies of tendon and ligament attachments are called enthesopathies. Enthesitis is one of enthesopathies and it is considered a characteristic sign of rheumatic diseases from the spondyloarthritis group, including peripheral spondyloarthritis. Therefore, enthesitis has been included in a number of clinical classifications for diagnosing these diseases. Clinical diagnosis of enthesitis is based on rather non-specific clinical signs and results of laboratory tests. It is believed that imaging examinations might improve diagnosis, particularly because numerous papers prove that differentiating enthesitis from other enthesopathic processes is possible. On the other hand, a number of authors report the lack of specific signs in imaging as well as typical histological and immunological features that would enable confirmation of clinical diagnosis of enthesitis. The first part of the publication presented theories on the etiopathogenesis of enthesitis (inflammatory, mechanical, autoimmune and associated with the synovio-entheseal complex) as well as on the formation of enthesophytes (inflammatory, molecular and mechanical). This paper - the second part of the article, is a review of the state-of-the-art on the ability of imaging examinations to diagnose enthesitis. It turns out that none of the enthesitis criteria used in imaging examinations is specific for inflammation. As enthesitis may be the only symptom of early spondyloarthritis (particularly in patients with absent HLA-B27 antigen), the lack of its unambiguous picture in ultrasound and magnetic resonance imaging prompts the search for other signs characteristic of spondyloarthritis and more specific features in imaging in order to make a diagnosis as early as possible. PMID- 26672490 TI - Unusual Presentation of Hepatocellular Carcinoma into Right iliac fossa: A Rare Entity. AB - Hepatocellular carcinoma (HCC) is the most common primary malignant hepatic tumour. Hepatocellular carcinoma presenting itself or extending into the right iliac fossa (RIF) is a very rare entity. We report on a rare case of hepatocellular carcinoma in a 60-year-old lady, presented with a mobile mass in the lower abdomen without cirrhosis, with normal alpha-feto protein levels (AFP) or any known risk factors for liver disease. HCC in this case was unusual in its presentation both in the patient as well as a disease. PMID- 26672491 TI - Mixed partial anomalous pulmonary venous drainage coexistent with an aortic valve abnormality - analysis of ultrasound diagnostics in a 10-year-old girl with Turner syndrome. AB - The authors present a case of echocardiographic diagnosis of a rare congenital cardiovascular anomaly in the form of mixed partial anomalous pulmonary veins connection in a 10-year-old girl with Turner syndrome and congenital mild stenosis of insufficient bicuspid aortic valve, made while diagnosing the causes of intestinal tract bleeding. The article presents various diagnostic difficulties leading to the delayed determination of a correct diagnosis, resulting from the absence of symptoms of circulatory failure in the early stage of the disease and the occurrence of severe and dominant auscultatory phenomena typical for congenital aortic valve defect which effectively masked the syndromes of increased pulmonary flow. The authors discuss the role of the impact of phenotypic characteristics of the Turner syndrome, in particular a short webbed neck restricting the suprasternal echocardiographic access and the presence of psychological factors associated with a long-term illness. The importance of indirect echocardiographic symptoms suggesting partial anomalous pulmonary veins connection in the presence of bicuspid aortic valve, e.g. enlargement of the right atrium and right ventricle, and paradoxical interventricular septum motion were emphasized in patients lacking ASD, pulmonary hypertension or tricupid and pulmonary valve abnormalities. The methodology of echocardiographic examination enabling direct visualization of the abnormal vascular structures was presented. Special attention was paid to the significance of highly sensitive echocardiographic projections: high right and left parasternal views in sagittal and transverse planes with patient lying on the side, with the use of two dimensional imaging and color Doppler. Finally, the limitations of echocardiography resulting from the visualization and tracking of abnormal vascular structures hidden behind ultrasound non-conductive tissues were indicated, as was the role of other diagnostic modalities, such as angio-CT and/or nuclear magnetic resonance. PMID- 26672492 TI - Persistent CMV infection after allogeneic hematopoietic stem cell transplantation in a CMV-seronegative donor-to-positive recipient constellation: Development of multidrug resistance in the absence of anti-viral cellular immunity. AB - We describe a case of persistent cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with discordant and high-risk (D-/R+) constellation of CMV serostatus. Despite the use of different and innovative antiviral strategies, viral replication could not be suppressed successfully promoting a protracted CMV colitis associated with severe gastrointestinal graft-versus-host disease (GI GVHD). We illustrate that the development of multidrug viral resistance, the failure to mount a CMV-specific cellular immune response, as confirmed by QuantiFERON((r))-CMV (Qiagen) assay, and the refractory GVHD requiring prolonged immunosuppression were the main factors contributing to persistent viral replication and the fulminant unfavorable course. PMID- 26672493 TI - Future role of ultrasound and MR imaging in prostate cancer: Editorial Comment on: T. Szopinski, A. Nowicki, F. Zatura, T. Golabek and P. Chlosta Novel trends in transrectal ultrasound imaging of prostate gland carcinoma. PMID- 26672494 TI - Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. AB - This article details the principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM). At the time of submission to JCSM, the corresponding author, on behalf of all co-authors, needs to certify adherence to these principles. The principles are as follows: (i) all authors listed on a manuscript considered for publication have approved its submission and (if accepted) publication as provided to JCSM; (ii) no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript; (iii) no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript; (iv) the submitted work is original and is neither under consideration elsewhere nor that it has been published previously in whole or in part other than in abstract form; (v) all authors certify that the work is original and does not contain excessive overlap with prior or contemporaneous publication elsewhere, and where the publication reports on cohorts, trials, or data that have been reported on before these other publications must be referenced; (vi) all original research work are approved by the relevant bodies such as institutional review boards or ethics committees; (vii) all conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively, and relevant sources of funding have been duly declared in the manuscript; (viii) the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelines on ethical publishing remain true; and (ix) If any of the aforementioned statements ceases to be true, the authors have a duty to notify the Editors of JCSM as soon as possible so that the available information regarding the published article can be updated and/or the manuscript can be withdrawn. PMID- 26672495 TI - Ultrasound-guided joint and soft tissue interventions. AB - Minor procedures with an injection needle are frequently performed in orthopedic clinics. They may be of a diagnostic, diagnostic and therapeutic or purely therapeutic nature. Ultrasound guidance while inserting the needle allows for a safe medicine administration and evacuation of fluid contents. It improves the efficacy of such procedures by ensuring accurate needle insertion in the target site. Ultrasound-guided procedures reduce the duration of treatment (e.g. medicines reach the target site directly; all fluid collections are removed, even multilocular ones) and minimize pain (by the selection of optimal access sites omitting tendons, vessels and peripheral nerves). This paper presents the principles of performing ultrasound-guided interventions. A detailed description of such a technique is provided and the most commonly injected medicines as well as their adverse reactions and contraindications are discussed. Attention is also paid to image optimization and the role of procedure site selection with the exclusion of other pathologies in the puncture site (such as tumors, foreign bodies and vascular or nerve pathologies). What is more, the author also discusses the principles of needle length and thickness selection as well as the manners of its insertion in relation to the transducer. Moreover, the principles of aseptics that are mandatory during such interventions are also presented and the way to protect transducers from the effects of chemical disinfectants is discussed. Furthermore, the paper contains numerous photographs of performed interventions. It is addressed to clinical practitioners and its aim is to facilitate and improve the efficacy of the procedures which are commonly performed in orthopedics. Ultrasound guidance of joint and soft tissue interventions should become a gold standard in all orthopedic clinics. PMID- 26672496 TI - The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers. AB - Methylmalonic acidemia (MMA) is a heterogeneous and severe autosomal recessive inborn error of metabolism most commonly caused by the deficient activity of the vitamin B12 dependent enzyme, methylmalonyl-CoA mutase (MUT). The main treatment for MMA patients is the dietary restriction of propiogenic amino acids and carnitine supplementation. Despite treatment, the prognosis for vitamin B12 non responsive patients remains poor and is associated with neonatal lethality, persistent morbidity and decreased life expectancy. While multi-organ pathology is a feature of MMA, the liver is severely impacted by mitochondrial dysfunction which likely underlies the metabolic instability experienced by the patients. Liver and/or combined liver/kidney transplantation is therefore sometimes performed in severely affected patients. Using liver specimens from donors and MMA patients undergoing elective liver transplantation collected under a dedicated natural history protocol (clinicaltrials.gov: NCT00078078), we employed proteomics to characterize the liver pathology and impaired hepatic metabolism observed in the patients. Pathway analysis revealed perturbations of enzymes involved in energy metabolism, gluconeogenesis and Krebs cycle anaplerosis. Our findings identify new pathophysiologic and therapeutic targets that could be valuable for designing alternative therapies to alleviate clinical manifestations seen in this disorder. PMID- 26672497 TI - Race and colorectal cancer screening compliance among persons with a family history of cancer. AB - AIM: To determine compliance to colorectal cancer (CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance. METHODS: We used the 2007 Health Information National Trends Survey and identified 1094 (27.4%) respondents (weighted population size = 21959672) without a family history of cancer and 3138 (72.6%) respondents (weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer. RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening (64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase (14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening (5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer: (54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and (56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for Hispanics. CONCLUSION: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of screening among high-risk groups. PMID- 26672498 TI - Altered Passive Eruption Complicating Optimal Orthodontic Bracket Placement: A Case Report and Review of Literature. AB - An unusual case of altered passive eruption with gingival hyperpigmentation and a Class I malocclusion in a 12-year-old girl having no previous history of medication is presented. The patient reported with spacing in the upper arch, moderate crowding in the lower arch, anterior crossbite and excessive gingival tissue on the labial surfaces of teeth in both the arches. The inadequate crown lengths made placement of the orthodontic brackets difficult. Preadjusted orthodontic brackets have a very precise placement protocol which can affect tooth movement in all 3 planes of space if violated. The periodontal condition was diagnosed as altered passive eruption Type IA. Interdisciplinary treatment protocols including periodontal surgical and orthodontic procedures were used. The periodontal surgical procedures were carried out prior to orthodontic therapy and the results obtained were satisfactory. It is suggested that orthodontists should be aware of conditions like altered passive eruption and modalities of management. In most instances, orthodontic therapy is not hindered. PMID- 26672501 TI - [Some notes on the near future]. PMID- 26672499 TI - Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain. AB - Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about "ceiling effect" or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed MU-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other MU-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain. PMID- 26672502 TI - [Schizophrenia: Recent data, future perspectives]. AB - Schizophrenia is one of the most incapacitating mental disorders. During the last years, new findings have been done in the physiopathology of the disorder such as the influence of inflammation, glial changes, neural oscillations and alterations in the gabaergic interneurons. Furthermore, new conceptualizations have led to research of new therapeutics both biological and psychotherapeutic. The perspectives of the diagnostic refinement and the new therapeutics allow us to be optimistic and imagine the possibility in the future when individuals with schizophrenia could fully integrate to the society. PMID- 26672503 TI - [Neuroprogression and cognition in Bipolar Disorders: A systematic review of cognitive performance in euthymic patients]. AB - In recent years, investigators have begun to consider the possibility of explaining the physiopathology of bipolar disorder from a neuroprogressive perspective. The evidence that supports the feasibility of such an approach is varied, and arises from neuroimaging studies, batteries of neurocognitive evaluations, and tests to identify the specific biomarkers of the disorder. The present article seeks to perform a review of the research that investigates the cognitive deficits in bipolar disorder. A bibliographic revision was performed of articles published between 1990 and 2015. Levels of cognitive performance were explored in both cross-sectional and longitudinal studies. The compiled studies signal the presence of altered cognitive function, even during periods of euthymia. However, there are contradictory results as to whether bipolar disorder presents a degenerative course. New lines of investigation suggest that only a percentage of individuals with bipolar disorder are affected in a progressive manner. It is of paramount importance to perform new longitudinal studies in high risk populations, so as to validate or refute a neuroprogressive model of cognitive deficits in patients with bipolar disorder. PMID- 26672504 TI - [Research in Psychopharmacology]. AB - Research in psychopharmacology began around 1950 with the description of antipsychotic effect of chlorpromazine followed shortly later with the mechanism of action of antidepressants. In these initial phases, pharmacy industry was open to knowledge and made efforts tending to the development to new drugs that showed efficacy and good safety profiles. In parallel development of theories attempting to find the etiology of psychiatric disorders acquired impulse. This review summarizes the new drugs for the treatment of psychiatric disorders currently under development and also presents a short list of the main biomarkers proposed for the diagnosis or the comprehension of the etiopathogeny in Psychiatry. Several questions arose when brain structures, biochemical pathways, proteins and genes began to be identified in the search for a better comprehension of etiopathogeny of mental disorders. Pharmaceutical industry virtually moved away from this field of research. Epistemological and methodological obstacles in psychopharmacological investigation together with the lack of priority given by industry to this field allow us to predict few advances for the treatment in Psychiatry in the short term. PMID- 26672505 TI - [The social model of disability in Argentina: Paradigm of decision-making support and safeguards in the new Argentine Civil Code]. AB - There has been a new framework with new laws and a new Code in Argentina in recent years in order to put its legal system in congruence with International Convenants on Human Rights and in particular with the Convention on the Rights of Persons with Disabilities. Through this new laws Argentina legal system recognize that persons with disabilities enjoy capacity on an equal basis with others in all aspects of life and the State shall take appropiate measures to provide access by persons with disabilities to the support they may require in excercising their legal capacity with safeguards. PMID- 26672506 TI - [Intensive pharmacovigilance of clozapine in Argentina]. AB - Approximately 12,000 individuals are treated with clozapine per year in Argentina. The use of this antipsychotic is associated with the occurrence of various side effects; the most serious of these is agranulocytosis, which can be fatal but reversible if detected early. For this reason, clozapine is under a pharmacovigilance intensive program centered by the National Administration of Drugs, Foods and Medical Devices. The present paper reviewed the current legislation for the use of clozapine in Argentina and compared the data obtained from the pharmacovigilance system with those reported in other countries. Further, difficulties that may arise during the reexposure of patients to clozapine are discussed. PMID- 26672507 TI - [Ernst Kretschmer: Body, mind and dimension]. PMID- 26672508 TI - [Constitution and character: Research on the constitution and the doctrine of temperaments (1921)]. PMID- 26672509 TI - Identifying Ureters In Situ Under Fluorescence During Laparoscopic and Open Colorectal Surgery. PMID- 26672510 TI - Synthesis of tetravalent LacNAc-glycoclusters as high-affinity cross-linker against Erythrina cristagalli agglutinin. AB - Four kinds of tetravalent double-headed glycoclusters [(LacNAc)4-DHGs] were designed with linkers of varying lengths consisting of alkanedioic carboxyamido groups (C6, C12, C18 and C24) between two bi-antennary LacNAc-glycosides. These glycoclusters served as high-affinity cross-linking ligands for the LacNAc binding lectin Erythrina cristagalli agglutinin (ECA). The binding activity and cross-linking between each ligand and ECA were characterized by a hemagglutination inhibition (HI) assay, isothermal titration calorimetry (ITC), a quantitative precipitation assay and dynamic light scattering (DLS). For the precipitation assay and DLS measurement, the synthesized (LacNAc)4-DHGs were found to be capable of binding and precipitating the ECA as multivalent ligands. ITC analysis indicated the binding of (LacNAc)4-DHGs was driven by a favorable enthalpy change. Furthermore, the entropy penalty from binding (LacNAc)4-DHGs clearly decreased in a spacer length-dependent manner. The binding affinities of flexible (LacNAc)4-DHGs (C18 and C24) with long spacers were found to be more favorable than those of the clusters having short spacers (C6 and C12). These results were supported by molecular dynamics simulations with explicit water molecules for the tetravalent glycoclusters with ECA. We concluded that the subtle modification in the epitope-presenting scaffolds exerts the significant effect in the recognition efficiency involved in the LacNAc moieties by ECA. PMID- 26672512 TI - Effect of nadroparin on anti-Xa activity during nocturnal hemodialysis. AB - BACKGROUND: Nadroparin is used during hemodialysis to prevent clotting of the extra corporeal system. During nocturnal hemodialysis patients receive an increased dosage of nadroparin compared to conventional hemodialysis. We tested whether the prescribed dosage regimen of nadroparin, according to Dutch guidelines, causes accumulation of nadroparin. METHODS: Anti-Xa levels were used as an indicator of nadroparin accumulation. Anti-Xa was measured photometrically in 13 patients undergoing nocturnal hemodialysis for 4 nights a week. Nadroparin was administered according to Dutch dosage guidelines. We assessed anti-Xa levels at 4 time points during 1 dialysis week: before the start of the first dialysis session of the week (baseline), prior to (T1) and after the last dialysis session of the week (T2) and before the first dialysis of the following week (T3). RESULTS: Patients received 71-95 IU/kg at the start of dialysis and another 50% of the initial dosage after 4 h with a total cumulative dosage of 128 +/- 24 IU/kg. Anti-Xa levels increased from 0.017 at baseline to 0.019 at T1 (p = 0.03). Anti-Xa levels were 0.419 +/- 0.252 IU/ml at T2 (p < 0.001 vs baseline and T1), whereas anti-Xa levels were not changed at T3 compared to baseline. CONCLUSION: Dosing of nadroparin according to Dutch guidelines in patients on nocturnal hemodialysis does not lead to accumulation of nadroparin. We therefore consider the Dutch dosage guidelines for nadroparin an effective and safe strategy. GENERAL SIGNIFICANCE: This article is the first to present data on anti-Xa activity during nocturnal hemodialysis which is a widely used and potentially dangerous therapy. PMID- 26672511 TI - The generality of kinase-catalyzed biotinylation. AB - Kinase-catalyzed protein phosphorylation is involved in a wide variety of cellular events. Development of methods to monitor phosphoproteins in normal and diseased states is critical to fully characterize cell signaling. Towards phosphoprotein analysis tools, our lab reported kinase-catalyzed labeling where gamma-phosphate modified ATP analogs are utilized by kinases to label peptides or protein substrates with a functional tag. In particular, the ATP-biotin analog was developed for kinase-catalyzed biotinylation. However, kinase-catalyzed labeling has been tested rigorously with only a few kinases, preventing use of ATP-biotin as a general tool. Here, biotinylation experiments, gel or HPLC-based quantification, and kinetic measurements indicated that twenty-five kinases throughout the kinome tree accepted ATP-biotin as a cosubstrate. With this rigorous characterization of ATP-biotin compatibility, kinase-catalyzed labeling is now immediately useful for studying phosphoproteins and characterizing the role of phosphorylation in various biological events. PMID- 26672514 TI - Bariatric Surgery in Women: A Boon Needs Special Care During Pregnancy. AB - Obesity is one of the leading causes of health related disorder and has reached epidemic proportions not only in developed nations but also in developing countries like India. Bariatric surgery has become a popular alternative for obese women planning pregnancy. A multidisciplinary approach involving the obstetrician, the bariatric surgeon and the nutritionist is required to manage pregnancy following bariatric surgery. Early consultation should be done to determine baseline nutritional status and the importance of regular check-ups must be explained. Nutritional supplementation should be tailored to the patient's status and the type of bariatric surgery performed. PMID- 26672513 TI - Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea. AB - AIM: To investigate associations between the tumor necrosis factor alpha (TNF alpha) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea. METHODS: Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF alpha polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-alpha polymorphisms, which are TNF-alpha -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-alpha genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC. RESULTS: None of the TNF-alpha polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-alpha -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-alpha -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-alpha -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-alpha polymorphisms which were significantly associated with HCC. They are TNF-alpha -1031/-863/-857/-308/-238 T C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-alpha -1031/-857/ 308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-alpha -1031/ 857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-alpha -1031/ 308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-alpha -1031/ 238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-alpha -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323). CONCLUSION: Although no single TNF-alpha polymorphism is associated with HCC in this study, some TNF alpha genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-alpha -1031 TT genotype may have a better prognosis than those with the CC genotype. PMID- 26672517 TI - Crop conundrum. PMID- 26672515 TI - Hypothesis: Is frequent, commercial jet travel by the general public a risk factor for developing cutaneous melanoma? AB - Melanoma incidence has been increasing worldwide over the past 50 years and various risk factors have been identified. Interestingly, multiple studies have shown a multifold increased risk of developing melanoma in jet pilots and airline crew. There has also been a dramatic increase in the availability and frequency of jet travel by the general population during this time period.. Therefore, it is hypothesized that frequent commercial jet travel may represent an additional risk factor for the development of cutaneous melanoma in susceptible individuals of the general public. PMID- 26672518 TI - A seismic shift. PMID- 26672519 TI - Science for peace. PMID- 26672516 TI - Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis. AB - OBJECTIVE: Human murine double minute 2 protein (MDM2) is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. METHODS: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan-Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. RESULTS: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05). In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427-0.881), and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05). The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05), and no association was observed in total populations and Asians (P>0.05). CONCLUSION: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but this single nucleotide polymorphism may be associated with genetic susceptibility of bladder cancer among Caucasians. PMID- 26672520 TI - Use data to challenge mental-health stigma. PMID- 26672532 TI - Nations approve historic global climate accord. PMID- 26672533 TI - Cancer studies clash over mechanisms of malignancy. PMID- 26672534 TI - Yellow Sea talks raise hopes for marine science. PMID- 26672535 TI - Europe's genetically edited plants stuck in legal limbo. PMID- 26672536 TI - German researchers pledge help in refugee crisis. PMID- 26672537 TI - The science myths that will not die. PMID- 26672538 TI - Chemistry: Why synthesize? PMID- 26672542 TI - Clinical trials: Crowdfunded trials doubly scrutinized. PMID- 26672543 TI - Innovation: Clean energy enters virtuous cycle. PMID- 26672544 TI - Disaster management: Design buildings for rapid evacuation. PMID- 26672545 TI - Authorship: Archives and citation miss equal authors. PMID- 26672546 TI - Training: Common doctorates across Europe. PMID- 26672547 TI - Correction. PMID- 26672548 TI - Quantum physics: Entanglement beyond identical ions. PMID- 26672549 TI - Climate science: A history of Greenland's ice loss. PMID- 26672550 TI - In retrospect: Twenty-five years of the sex-determining gene. PMID- 26672552 TI - Rarity in mass extinctions and the future of ecosystems. AB - The fossil record provides striking case studies of biodiversity loss and global ecosystem upheaval. Because of this, many studies have sought to assess the magnitude of the current biodiversity crisis relative to past crises-a task greatly complicated by the need to extrapolate extinction rates. Here we challenge this approach by showing that the rarity of previously abundant taxa may be more important than extinction in the cascade of events leading to global changes in the biosphere. Mass rarity may provide the most robust measure of our current biodiversity crisis relative to those past, and new insights into the dynamics of mass extinction. PMID- 26672553 TI - Multi-element logic gates for trapped-ion qubits. AB - Precision control over hybrid physical systems at the quantum level is important for the realization of many quantum-based technologies. In the field of quantum information processing (QIP) and quantum networking, various proposals discuss the possibility of hybrid architectures where specific tasks are delegated to the most suitable subsystem. For example, in quantum networks, it may be advantageous to transfer information from a subsystem that has good memory properties to another subsystem that is more efficient at transporting information between nodes in the network. For trapped ions, a hybrid system formed of different species introduces extra degrees of freedom that can be exploited to expand and refine the control of the system. Ions of different elements have previously been used in QIP experiments for sympathetic cooling, creation of entanglement through dissipation, and quantum non-demolition measurement of one species with another. Here we demonstrate an entangling quantum gate between ions of different elements which can serve as an important building block of QIP, quantum networking, precision spectroscopy, metrology, and quantum simulation. A geometric phase gate between a (9)Be(+) ion and a (25)Mg(+) ion is realized through an effective spin spin interaction generated by state-dependent forces induced with laser beams. Combined with single-qubit gates and same-species entangling gates, this mixed element entangling gate provides a complete set of gates over such a hybrid system for universal QIP. Using a sequence of such gates, we demonstrate a CNOT (controlled-NOT) gate and a SWAP gate. We further demonstrate the robustness of these gates against thermal excitation and show improved detection in quantum logic spectroscopy. We also observe a strong violation of a CHSH (Clauser-Horne Shimony-Holt)-type Bell inequality on entangled states composed of different ion species. PMID- 26672554 TI - Hybrid quantum logic and a test of Bell's inequality using two different atomic isotopes. AB - Entanglement is one of the most fundamental properties of quantum mechanics, and is the key resource for quantum information processing (QIP). Bipartite entangled states of identical particles have been generated and studied in several experiments, and post-selected or heralded entangled states involving pairs of photons, single photons and single atoms, or different nuclei in the solid state, have also been produced. Here we use a deterministic quantum logic gate to generate a 'hybrid' entangled state of two trapped-ion qubits held in different isotopes of calcium, perform full tomography of the state produced, and make a test of Bell's inequality with non-identical atoms. We use a laser-driven two qubit gate, whose mechanism is insensitive to the qubits' energy splittings, to produce a maximally entangled state of one (40)Ca(+) qubit and one (43)Ca(+) qubit, held 3.5 micrometres apart in the same ion trap, with 99.8 +/- 0.6 per cent fidelity. We test the CHSH (Clauser-Horne-Shimony-Holt) version of Bell's inequality for this novel entangled state and find that it is violated by 15 standard deviations; in this test, we close the detection loophole but not the locality loophole. Mixed-species quantum logic is a powerful technique for the construction of a quantum computer based on trapped ions, as it allows protection of memory qubits while other qubits undergo logic operations or are used as photonic interfaces to other processing units. The entangling gate mechanism used here can also be applied to qubits stored in different atomic elements; this would allow both memory and logic gate errors caused by photon scattering to be reduced below the levels required for fault-tolerant quantum error correction, which is an essential prerequisite for general-purpose quantum computing. PMID- 26672555 TI - Spatial and temporal distribution of mass loss from the Greenland Ice Sheet since AD 1900. AB - The response of the Greenland Ice Sheet (GIS) to changes in temperature during the twentieth century remains contentious, largely owing to difficulties in estimating the spatial and temporal distribution of ice mass changes before 1992, when Greenland-wide observations first became available. The only previous estimates of change during the twentieth century are based on empirical modelling and energy balance modelling. Consequently, no observation-based estimates of the contribution from the GIS to the global-mean sea level budget before 1990 are included in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. Here we calculate spatial ice mass loss around the entire GIS from 1900 to the present using aerial imagery from the 1980s. This allows accurate high resolution mapping of geomorphic features related to the maximum extent of the GIS during the Little Ice Age at the end of the nineteenth century. We estimate the total ice mass loss and its spatial distribution for three periods: 1900-1983 (75.1 +/- 29.4 gigatonnes per year), 1983-2003 (73.8 +/- 40.5 gigatonnes per year), and 2003-2010 (186.4 +/- 18.9 gigatonnes per year). Furthermore, using two surface mass balance models we partition the mass balance into a term for surface mass balance (that is, total precipitation minus total sublimation minus runoff) and a dynamic term. We find that many areas currently undergoing change are identical to those that experienced considerable thinning throughout the twentieth century. We also reveal that the surface mass balance term shows a considerable decrease since 2003, whereas the dynamic term is constant over the past 110 years. Overall, our observation-based findings show that during the twentieth century the GIS contributed at least 25.0 +/- 9.4 millimetres of global mean sea level rise. Our result will help to close the twentieth-century sea level budget, which remains crucial for evaluating the reliability of models used to predict global sea level rise. PMID- 26672559 TI - Gallbladder Volvulus: A Single Institution's Experience over Two Years. PMID- 26672558 TI - Nevirapine: Most Common Cause of Cutaneous Adverse Drug Reactions in an Outpatient Department of a Tertiary Care Hospital. AB - INTRODUCTION: Skin is the most commonly involved organ in adverse drug reactions. Most of the cutaneous adverse drug reactions (CADRs) being of mild to moderate severity are likely to be diagnosed and treated in an outpatient setting. Consequently, knowledge regarding morphological pattern, severity and drugs implicated in causation of these CADRs has important implications for healthcare personnel. AIM: To determine the current clinical pattern of CADRs and to assess their causality and severity with the help of standard scales. STUDY DESIGN AND SETTING: A prospective, observational study was conducted in the outpatient department of skin and venereal disease in a tertiary care hospital. MATERIALS AND METHODS: Patients with suspected CADR after consumption of systemic drug(s) were enrolled in the study. Data regarding demographics, clinical manifestations of CADR, drug history preceding the reaction, concomitant illness, relevant laboratory investigations etc was obtained. This data was then analysed for morphological pattern, causality and severity. CADRs with causality assessment possible and above on the basis of World Health Organization-Uppsala Monitoring Centre causality assessment system were considered for analysis. STATISTICS: Descriptive statistics were used to express results of pattern, severity and causality of CADRs. RESULTS: Ninety patients were enrolled in the study. Male to female ratio for CADRs was 1:2.33. Maculopapular rash was most commonly encountered CADR in 76.67% cases followed by urticaria (8.89%), Stevens-Johnson syndrome (4.4%) and fixed dose eruptions (3.33%). Antiretrovirals were implicated in 75.56% (68/90) of CADRs. Nevirapine was suspected in 52 out of 90 (57.77%) cases of CADRs which included 39 cases of maculopapular rash, five cases of urticaria, four cases of Stevens-Johnson syndrome, and two cases each of pustular rash and angioedema respectively. Antimicrobials, antiepileptics and Non steroidal Anti-inflammatory Drugs (NSAIDs) were other suspected drugs. CONCLUSION: Antiretrovirals especially nevirapine was implicated in variety of CADRs ranging from maculopapular rash to life-threatening reactions like Stevens Johnson syndrome in an outpatient setting. Women were twice as susceptible as men for CADRs. PMID- 26672557 TI - Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors. AB - Senile plaques comprised of Abeta peptides are a hallmark of Alzheimer's disease (AD) brain, as are activated glia that release inflammatory molecules, including eicosanoids. Previous studies have demonstrated that amyloid precursor protein (APP) and Abeta levels can be increased through activation of thromboxane A2 prostanoid (TP) receptors on neurons. We demonstrate that TP receptor regulation of APP expression depends on Galphaq-signaling and conventional protein kinase C isoforms. Importantly, we discovered that Galphaq-linked prostaglandin E2 and leukotriene D4 receptors also regulate APP expression. Prostaglandin E2 and thromboxane A2, as well as total APP levels, were found to be elevated in the brains of aged 5XFAD transgenic mice harboring Abeta plaques and activated glia, suggesting that increased APP expression resulted from eicosanoid binding to Galphaq-linked neuronal receptors. Notably, inhibition of eicosanoid synthesis significantly lowered brain APP protein levels in aged 5XFAD mice. These results provide new insights into potential AD therapeutic strategies. PMID- 26672561 TI - Prediction of Malignancy in Bethesda Category III Nodules: Application of Thyroid Imaging Reporting System. PMID- 26672560 TI - Xanthogranulomatous Cholecystitis. PMID- 26672562 TI - Disparities in Stage at Presentation and Treatment of Colorectal Cancer among Hispanic and Non-Hispanic White Patients. PMID- 26672563 TI - Gastric Bypass with Unknown Intestinal Malrotation: How I Do It. PMID- 26672564 TI - Ampullary Gangliocytic Paraganglioma with Lymph Node Metastasis. PMID- 26672565 TI - Novel Ergonomic Approach (Split-leg) for Transinguinal Groin Hernia Repair. PMID- 26672566 TI - Immediate Tissue-expander Breast Reconstruction Using a Skin Flap with Thick Subcutaneous Tissue: A Preliminary Study on Selective Patients. PMID- 26672567 TI - Addition of Colectomy to Pancreaticoduodenectomy, Is it Safe? PMID- 26672568 TI - Identification of Ureter during Colorectal Surgery Cannot Always Avoid Ureteral Injury: Duplicated Collecting System. PMID- 26672569 TI - Rectal Prolapse in Octogenarians: Does Surgery Impact Daily Activity? PMID- 26672570 TI - Abdominal Wall Reconstruction for Large Ventral Hernias in the Octogenarian. PMID- 26672571 TI - Utility of Diagnostic Tests during Hospitalizations for Incision and Drainage of Pediatric Soft Tissue Infections. PMID- 26672572 TI - Efficacy of Vacuum Sealing Drainage after Incision of Perianal Abscess: Preliminary Experience. PMID- 26672573 TI - Central Pancreatectomy with Pancreaticogastrostomy for the Treatment of a Solid pseudopapillary Neoplasm. PMID- 26672574 TI - Increased Incidence of Blood Product Transfusions among Transplant Patients Treated with Linezolid Therapy: A Retrospective, Cohort Study. PMID- 26672575 TI - Four Tips and Tricks for Performing Laparoscopic Gastric Bypass. PMID- 26672576 TI - Laparoscopic Splenectomy for Giant Splenic Cyst. PMID- 26672577 TI - Delayed Gastric Emptying after Pancreaticoduodenectomy: Analysis of Associated Risk Factors. PMID- 26672578 TI - Massive Transfusion for Trauma in a Lower Middle Income Country. PMID- 26672579 TI - Predictive Factors of Ventilator Dependency after Colon and Rectal Surgery. AB - There is limited data analyzing ventilator dependency by operative diagnoses and types of the procedures performed in colorectal surgery. We sought to identify predictive factors of ventilator dependency in colorectal surgery and investigate complication rates across various colorectal procedures. The National Surgical Quality Improvement Program database was used to examine the clinical data of patients with ventilator dependency for more than 48 hours after colorectal resection during 2005-2013. Multivariate regression analysis was performed to identify predictors of ventilator dependency. A total of 219,716 patients who underwent colorectal resection were identified. The rate of ventilator dependency was 3.9 per cent. The rate varied significantly based on patient diagnosis; with the highest rate seen in patients with acute mesenteric ischemia (25.9%). The highest risk of ventilator dependency according to the patients indication of surgery, type of the procedure, and preoperative factors exist in lower gastrointestinal bleeding [adjusted odds ratio (AOR): 77.44, P < 0.01], total colectomy (AOR: 1.58, P = 0.04), and American Society of Anesthesiologists classification of three or greater (AOR: 2.52, P < 0.01). Also, serum albumin level (AOR: 0.67, P < 0.01) seems to be associated with ventilator dependency. The overall rate of ventilator dependency is 3.9 per cent in colorectal surgery. However, depending on the indication for surgery, rates can be as high as 25.9 per cent. American Society of Anesthesiologist score can predict the risk of postoperative ventilator dependency in patients undergoing colorectal surgery. Serum albumin level is reversely associated with postoperative ventilator dependency. PMID- 26672580 TI - Anal Adenocarcinoma: Outcomes in an Uncommon Malignancy. AB - Adenocarcinoma is an uncommon malignancy of the anal canal. Although it is recognized as an aggressive disease, optimal management and long-term outcomes are not well established. Patients diagnosed with anal adenocarcinoma were identified from a cancer database. Their charts were reviewed for patient and disease characteristics, management, and outcomes. Eighteen patient charts from 1997 to 2012 were reviewed. Nine patients presented with stage II disease, five with stage III, three with stage IV, and one was inadequately staged before chemoradiation. One patient refused treatment, one patient went straight to abdominoperineal resection, 13 patients underwent initial chemoradiation therapy, and three underwent palliative chemotherapy. Of the 13 patients who received neoadjuvant therapy, eight underwent subsequent radical resection; three progressed during neoadjuvant and became unresectable, one had complete pathologic response and was observed, and one did not complete neoadjuvant and was lost to follow-up. Two patients with stage II disease were disease free over eight years, and one was disease free after 26 months; four patients had persistent or recurrent local disease, and 10 developed metastatic disease. Seven patients died with disease at a median 16 months, and the other seven were alive with disease at a median follow-up of 10 months. Patients with anal adenocarcinoma present at advanced stages, and cure is rare. Although chemoradiation followed by abdominoperineal resection is the most common management strategy, the potential for curative resection and long-term disease free survival is minimal, regardless of stage at presentation. PMID- 26672581 TI - Abdominal MRI without Enteral Contrast Accurately Detects Intestinal Fibrostenosis in Patients with Inflammatory Bowel Disease. AB - Patients with inflammatory bowel disease (IBD) presenting for surgical evaluation require thorough small bowel surveillance as it improves accuracy of diagnosis (ulcerative colitis versus Crohn's) and differentiates those who may respond to nonoperative therapy, preserving bowel length. MRI has not been validated conclusively against histopathology in IBD. Most protocols require enteral contrast. This study aimed to 1) evaluate the accuracy of MRI for inflammation, fibrosis, and extraluminal complications and 2) compare MRI without enteral contrast to standard magnetic resonance enterography. Adults with Crohn's disease or ulcerative colitis who underwent abdominal MRI and surgery were retrospectively reviewed. Of 65 patients evaluated, 55 met inclusion criteria. Overall sensitivity and specificity of MRI for disease involvement localized by segment were 93 per cent (95% confidence interval = 89.4-95.0) and 95 per cent (95% confidence interval = 92.3-97.0), respectively (positive predictive value was 86%, negative predictive value was 98%). Sensitivity and specificity between MRI with and without oral and rectal contrast were similar (96% vs 91% and 99% vs 94%, P > 0.10). As were positive predictive value and negative predictive value (85% vs 96%, P = 0.16; 97% vs 99%, P = 0.42). Magnetic resonance is highly sensitive and specific for localized disease involvement and extraluminal abdominal sequelae of IBD. It accurately differentiates patients who have chronic transmural (fibrotic) disease and thus may require an operation from those with acute inflammation, whose symptoms may improve with aggressive medical therapy alone. MRI without contrast had comparable diagnostic yield to standard magnetic resonance enterography. PMID- 26672582 TI - Duodenal Adenocarcinoma: Profile and Predictors of Survival Outcomes. AB - Duodenal adenocarcinoma is rare. We aimed to evaluate survival outcome and prognostic factors for survival in patients with duodenal adenocarcinoma in recent years, marked by advancement in chemotherapy for gastrointestinal cancers. All patients treated for duodenal adenocarcinoma at our institution between January 2000 and July 2013 were reviewed. Thirty-nine patients were identified: 27 operative patients [21(53.8%) curative and 6 (15.4%) palliative operations] and 12 nonoperative patients [primary systemic chemotherapy, 4 (10.3%), palliative radiotherapy, 1 (2.6%), and no treatment, 7 (17.9%)]. Curative resections included 13 pancreaticoduodenectomies and eight segmental resections. Median overall survival (OS) for entire cohort was 14.4 months. Median OS and one , three-, and five-year OS were operative group (41.4 months; 79.1%, 50.6%, and 10.6%, respectively); nonoperative group (7.4 months; 25.0%, 8.3%, and 0%, respectively); curative surgery (45.4 months; 92.9%, 62.5%, and 16.7%, respectively) and palliative surgery (5.4 months; 33.3%, 16.7%, and 0%, respectively). Female gender (P = 0.04), curative resection (P = 0.03), nodal metastasis (P = 0.047) and advanced T stage (P = 0.047) were predictive of OS. Two factors were independently predictive of OS--female gender and curative resection. Overall survival still hinges on curative resection. This favors early detection. Adjuvant treatment modalities such as chemotherapy and radiation require further investigation. PMID- 26672583 TI - Management of the Open Abdomen in Obese Trauma Patients. AB - Obesity incidence in the trauma population is increasing. Abdominal compartment syndrome has poor outcomes when left untreated. Surgeons may treat obese patients differently because of concern for increased morbidity and mortality. We studied the effects of body mass index (BMI) on resource utilization and outcome. An Institutional Review Board-approved retrospective review of trauma patients requiring temporary abdominal closure (TAC) was performed. Patients were stratified as follows: Group 1-BMI = 18.5 to 24.9 kg/m(2), Group 2-BMI = 25 to 29.9 kg/m(2), Group 3-BMI = 30 to 39.9 kg/m(2), Group 4-BMI >= 40 kg/m(2). Demographic data, illness severity as defined by Injury Severity Score, Acute Physiology and Chronic Health Evaluation Score Version II and Simplified Acute Physiology Score Version II scores, resource utilization, fascial closure rate, and survival were collected. About 380 patients required TAC. Median age of Group 1 was significantly lower than Groups 2 and 3 (P = 0.001). Severity of illness did not differ. Group 4 had a longer intensive care unit stay compared with Groups 1 and 2 (P = 0.005). Group 4 required mechanical ventilation longer than Group 1 (P = 0.027). Hospital stay, fascial closure, and survival were equivalent. Obese trauma patients with TAC have a longer intensive care unit stay and more ventilator days, but there is no difference in survival or type of closure. TAC can be used safely in trauma patients with a BMI >= 30 kg/m(2). PMID- 26672584 TI - Double Prosthetic Repair for Complex Incisional Hernia Repair: Long-term Results and Evolution of the Technique. AB - No single approach has emerged as the best way to close complex incisional hernias. The aim of this report is to present the long-term results with a double prosthetic repair. In this prospective observational study over 12 years (Group 1, 8 years; Group 2, 4 years), the following data were collected: age, gender, previous surgery, comorbidities, situation and size of defect, hospital stay, postoperative complications, and recurrence. There were 53 lateral cases and 31 midline cases. About 88.6 per cent of the lateral defects were repaired without needing to approach the intra-abdominal cavity (Type I), whereas in the patients with large medial defects this was only achieved in 6.5 per cent of the cases (93.5% required a Type II). The average length of the defects was 18 cm. Global morbidity was 18 per cent early, and 7 per cent late. The statistical analysis over time shows significant differences in the operative time, hospital stay, and consumption of analgesics (P < 0.001). The recurrence rate has not varied despite the modifications to the technique (use of lighter meshes and fixation with tacks and glue). Complex abdominal wall defects can be corrected using the double prosthetic repair technique with low morbidity rates and with practically no long term recurrence. The combination of two meshes reduces their density and the use of combined fixation (tacks + glue) improves postoperative recovery. PMID- 26672585 TI - Repair of Small and Medium Size Umbilical Hernias with the "Proceed Ventral Patch" in the Preperitoneal Position. AB - Small- and medium-sized ventral hernias including umbilical hernias can be repaired using prosthetic patches placed in the peritoneum. However, bowel associated complications secondary to intraperitoneally placed hernia patches have been reported. Herein, we report the outcome of small and medium umbilical hernia closure with prosthetic hernia patches in the preperitoneal space. Prospectively collected data of patients undergoing repair of small- and medium sized umbilical hernias with the proceed ventral patch in a primary care hospital in Germany was retrospectively analyzed. A total of 39 cases, including 11 female and 28 male patients, were managed with prosthetic patches in the preperitoneal position. Small-sized patches were implantated in 16 cases, whereas medium-sized patches were used in 23 cases. The median duration of surgery was 40 minutes. The median length of hospital stay was four days. Four minor complications were recorded (10.3%) and the rate of recurrence was 2.6 per cent within a follow-up period of up to 30 months. Small and medium size umbilical hernias can be effectively closed with prosthetic patches placed in the preperitoneal space without risk of serious bowel associated complications. PMID- 26672586 TI - Early Outcome of Treatment of Chronic Mesenteric Ischemia. AB - There are limited data regarding long-term outcomes of chronic mesenteric ischemia (CMI) of the intestine. We sought to identify treatment outcomes of CMI. The NIS database was used to identify patients admitted for the diagnosis of CMI between 2002 and 2012. Multivariate analysis using logistic regression was performed to quantify outcomes of CMI. A total of 160,889 patients were admitted for chronic vascular insufficiency of intestine; of which 7,906 patients underwent surgical/endovascular treatment for CMI. Among patients who underwent surgery 62 per cent had endovascular treatment and 38 per cent had open vascular treatment. Need of open surgery (adjusted odds ratio (AOR): 5.13, P < 0.01) and age >=70 years (AOR: 3.41, P < 0.01) had strong associations with mortality of patients. Open vascular treatment has higher mortality (AOR: 5.07, P < 0.01) and morbidity (AOR: 2.14, P < 0.01). However, endovascular treatment had higher risk of postoperative wound hematoma (AOR: 2.81, P < 0.01). Most patients admitted for CMI are treated with endovascular treatment. Endovascular treatment has the advantage of lower mortality and morbidity. Need to open surgery and age >=70 years have strong associations with mortality of patients. PMID- 26672587 TI - Vertical Tunnel-based Low-site Peritoneal Dialysis Catheter Implantation Decreases the Incidence of Catheter Malfunction. AB - Peritoneal dialysis (PD) is often complicated by catheter dysfunction. We designed a PD catheter implantation technique to reduce catheter dysfunction. Between June 2008 and 2012, 89 patients with end-stage renal disease were enrolled into a prospective study and randomly assigned to receive traditional catheter implantation by open surgery (n = 41) or vertical tunnel-based low-site PD catheter implantation (n = 48). Both procedures used Baxter straight double cuffed Tenckhoff catheters. The novel implantation technique involves a low-site (7 cm above the midpoint of the pubic symphysis), individually tailored intra abdominal segment, and increased vertical subcutaneous tunnel. Patients were followed for 1-year after procedure. The vertical tunnel-based low-site method implanted catheters were 3.7 +/- 0.9 cm long, with an 11.3 +/- 0.9 cm intra abdominal segment. The incidence of postoperative bleeding, PD fluid leakage, outer cuff extrusion, inflow or outflow pain, peritonitis, tunnel inflammation, or exit-site infection did not differ significantly between the two surgical techniques; however, the incidence of catheter displacement and noncatheter displacement malfunctions after the novel technique (4.2%) was significantly lower than that in traditional open surgery (19.5%, P < 0.05). In conclusions, vertical tunnel-based low-site PD catheter implantation can significantly reduce the occurrence of PD catheter malfunction, particularly catheter displacement. PMID- 26672588 TI - Sartorius Muscle Flaps for Vascular Groin Wound Complications. AB - Sartorius myoplasty (SM) has been used as an adjunct for soft tissue coverage in vascular groin wound complications. However, the reliability of SM as a primary muscle flap has been questioned. The purpose of this study is to determine the reliability of SM performed by vascular surgeons in the management of vascular groin wound complications. A retrospective review was performed on all patients who underwent SM from 1997 to 2012. The three indications for SM were prophylactic, infection, and noninfectious wound complication. Failure of SM was defined as operative reintervention for bleeding, persistent wound drainage, or infection. A total of 99 patients underwent 103 SM procedures. The patients were 43 per cent male and 57 per cent female; the mean age was 69 years. The indication for SM was infectious in 62 cases (60%), prophylactic in 21 cases (20%), and noninfectious in the remaining 20 cases. Failure of SM occurred in 11 cases (11%). Of these, salvage bypass and/or salvage muscle flap was required in eight cases (73%). When salvage bypass was required, extra-anatomic obturator bypass was performed in 80 per cent of cases. Salvage wound coverage included rectus abdominus flap (60%), rotational flap (20%), and skin grafting (20%).Seventy-three per cent of failures came from the infectious wound group. The most common reason for SM failure was hemorrhage (45%). In 82 per cent of the cases, the sartorius muscle was still viable at reoperation and was used for continued muscle coverage. SM performed by the vascular surgeon provides reliable soft tissue coverage for vascular groin wound complications and should be used as the primary muscle flap in the majority of patients. In cases of SM failure, the vascular surgeon should consider other more extensive muscle flap options. PMID- 26672589 TI - Endovascular Therapy for Acute Mesenteric Ischemia: an NSQIP Analysis. AB - Acute mesenteric ischemia (AMI) continues to carry high morbidity and mortality. Endovascular strategies have been increasingly used in the management of AMI. The purpose of this study was to evaluate the impact of endovascular therapy on outcomes of patients with AMI. The National Surgical Quality Improvement Program database was queried to identify all patients requiring emergency surgical intervention for AMI. Demographics, clinical data, interventions, and outcomes were extracted. Patients were compared according to treatment (endovascular versus hybrid versus open revascularization). Over the six-year study period, a total of 439 patients were found to have AMI [27 (6.2%) endovascular, 23 (5.2%) hybrid, and 389 (88.6%) open revascularization]. A total of 16 (59.3%) patients in the endovascular group avoided laparotomy. There was a trend toward lower transfusion requirements (intraoperative transfusion: 3.7% for endovascular vs 17.4% for hybrid vs 19.3% for open, adjusted. P = 0.127) and complications in particular pneumonia (22.2% vs 39.1% vs 27.8%, respectively, Adj. P = 0.392) and sepsis (25.9% vs 21.7% vs 35.5%, adjusted P = 0.260). Endovascular therapy was associated with a 2.5-fold decrease in the risk of death [odds ratio, 95% confidence interval: 0.4 (0.2, 0.9), adjusted P = 0.018]. In this analysis of morbidity and mortality, endovascular therapy was associated with decreased need for laparotomy and a trend toward lower transfusion requirements and complications, in particular pneumonia and sepsis. Endovascular first therapy was associated with a 2.5-fold decrease in the risk of death. Further prospective evaluation of these results is warranted. PMID- 26672590 TI - Transfers for Hand Surgery Correlate with Increased Reoperations for Complications. AB - Wrist, hand, and finger trauma are the most common nonlethal injuries presenting to emergency departments. In Tennessee, lack of available hand care, particularly the need for emergency hand surgery, could be detrimental to patient outcomes. This is a retrospective outcomes study of patients requiring revisional hand surgeries. Patients were identified and stratified by distance to Vanderbilt University Medical Center (VUMC) to determine if patient complications increase with distance from VUMC. As distance of patient county of residence from VUMC increased, per cent of patients without a complication decreased (P < 0.0001). Counties without 24/7 comprehensive hand call also showed a distance difference in complication rates. Per capita income and mean household income showed no effect on complications. Distance from treating facility is correlated with patient outcomes and need for revisional surgery. Limitations in care availability in Tennessee are not specific to hand surgery. If the trend toward poorer outcomes as a result of limited local care availability extends to other specialties, this could have implications regarding health-care realignment. Specifically for patients with complex injuries or conditions that will be referred to centralized flagship hospitals, increases in patient travel may limit positive outcomes. PMID- 26672591 TI - Daily Incision Cleansing with Alcohol Reduces the Rate of Surgical Site Infections: A Pilot Study. AB - Surgical site infections (SSIs) represent a significant source of preventable patient morbidity and hospital expense. Our objective was to assess the role of postoperative incisional alcohol cleansing in decreasing the rates of SSI as compared with standard care (control). Patients undergoing clean-contaminated abdominal operations at a single center were included. Prospectively collected data on control patients were compared with patients treated with daily postoperative alcohol-based surgical site cleansing (70% isopropyl alcohol) for the primary outcome of an SSI within the first 30 postoperative days. A total of 93 patients were included, 56 managed with standard care and 37 managed with the addition of daily alcohol cleansing. A significantly lower rate of SSI in the group managed with daily alcohol cleansing was observed (13% vs 32%, P = 0.04). This study suggests a role for adding daily incisional alcohol cleansing to further reduce the rate of SSIs. PMID- 26672592 TI - Acute Genital Edema during Peritoneal Dialysis: A Review for Surgeons. AB - Acute genital edema (AGE) is an infrequent but disruptive complication in patients on continuous ambulatory peritoneal dialysis. It is a common manifestation of dialysate leakage caused by inguinal, umbilical, femoral, or incisional hernias; peritoneal tears; leaks around the dialysis catheter; trauma; fluid overload; and malignancy. The evaluation of AGE begins with a history and physical exam. However, the physical exam in these patients is often indeterminate. Several diagnostic measures exist to evaluate and guide management of AGE occurring during continuous ambulatory peritoneal dialysis but little agreement exists on an optimum method. We have conducted a review of the literature on the evaluation and management of AGE and present a summary of the data. CT peritoneography and peritoneal scintigraphy have been used extensively to evaluate AGE although no comparative studies exist. MRI peritoneography has also been described. CT peritoneography offers more anatomical detail but may not be as sensitive as peritoneal scintigraphy in detecting a peritoneal fluid leak as the cause for AGE. CT is also more costly and subjects the patient to more radiation. MRI is a noncontrast study without radiation risk, but has not been studied to the same degree. If testing is equivocal or bilateral hernias are suspected, diagnostic laparoscopy is helpful and can be combined with hernia repair. Whether the etiology is a leak or tear, low-volume peritoneal dialysis (PD) or cessation of PD for two to four weeks will allow closure. However, hernias almost always require operative repair with mesh usually without disrupting PD. PMID- 26672593 TI - Ultrasound presentation of abdominal non-Hodgkin lymphomas in pediatric patients. AB - INTRODUCTION: Burkitt's lymphoma accounts for approximately 25% of lymphomas diagnosed in children of developmental age. The tumor is localized mainly in the intestine (usually in the ileocecal region), mesenteric lymph nodes and extraperitoneal space. The clinical symptoms are non-specific and include: abdominal pain, vomiting, gastrointestinal bleeding, and acute abdomen suggesting appendicitis or intestinal intussusception. On ultrasound examination, Burkitt's lymphoma may manifest itself in various ways, depending on the origin of the lesion. AIM: The aim of this paper was to review the ultrasound manifestation of abdominal Burkitt's lymphoma in children. MATERIAL AND METHODS: The analysis included 15 pediatric patients with Burkitt's non-Hodgkin lymphoma in the abdominal cavity. The mean age of the patients was 9.5. Abdominal and gastrointestinal ultrasound examinations were conducted using a Siemens scanner with a convex transducer of 3.5-5 MHz and linear array transducer of L4 - 7.5 MHz. RESULTS: Ultrasound examinations conducted in the group of 15 patients revealed pathological masses localized in the gastric wall in 3 patients (20%), in the ileocecal region in 10 patients (67%) and a disseminated process in 2 patients (13%). In 12 patients with a diagnosed Burkitt's non-Hodgkin lymphoma in an extragastric localization, differences in the morphology of the lesions were observed. CONCLUSIONS: The clinical and ultrasound picture of abdominal Burkitt's lymphoma in children is variable. A careful ultrasound assessment of all abdominal organs conducted with the use of convex and linear probes increases the chances of establishing an adequate diagnosis. PMID- 26672594 TI - Trastuzumab-induced corneal ulceration: successful no-drug treatment of a "blind" side effect in a case report. AB - BACKGROUND: We report the first successful treatment of limbal lesions and corneal erosion experienced by a breast cancer patient undergoing trastuzumab treatment. CASE PRESENTATION: A 49-year-old Caucasian woman with early stage breast cancer was treated with adjuvant trastuzumab and subsequently showed persistent bilateral corneal marginal infiltrates resistant to topical steroid and antibiotic treatment. Autologous serum was applied in the conjunctival sac as an experimental treatment to antagonize the inhibitory effect of the HER2 receptor antibody on the corneal epithelial cells. Topical application of autologous serum led to rapid improvement of the ulcerative keratitis, with complete healing of the corneal defect after 7 days. Continued administration of the serum allowed the resumption of trastuzumab therapy without any further side effects. CONCLUSIONS: Persistent bilateral corneal marginal infiltrates may occasionally arise as a side effect of trastuzumab treatment. Topical medication with autologous serum may be an effective therapeutic option for the ocular side effects of trastuzumab therapy. PMID- 26672595 TI - Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease. AB - BACKGROUND/AIMS: We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. METHODS: Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index >=5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. RESULTS: Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)<95% (OR 3.21, 95%C.I. 1.02-7.34; p = 0.04). Prevalence of OSA tended to be higher in patients with, than in those without, carotid plaques (64% vs 40%; p = 0.08). Carotid plaques were independently associated with %time at SaO2<90% >1 (OR 6.30, 95%C.I. 1.02-12.3; p = 0.01). CONCLUSIONS: In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients. PMID- 26672596 TI - "A constant struggle to receive mental health care": health care professionals' acquired experience of barriers to mental health care services in Rwanda. AB - BACKGROUND: In Rwanda, many people are still mentally affected by the consequences of the genocide and yet mental health care facilities are scarce. While available literature explains the prevalence and consequences of mental disorders, there is lack of knowledge from low-income countries on health care seeking behavior due to common mental disorders. Therefore, this study sought to explore health care professionals' acquired experiences of barriers and facilitators that people with common mental disorders face when seeking mental health care services in Rwanda. METHODS: A qualitative approach was applied and data was collected from six focus group discussions (FGDs) conducted in October 2012, including a total of 43 health care professionals, men and women in different health professions. The FGDs were performed at health facilities at different care levels. Data was analyzed using manifest and latent content analysis. RESULTS: The emerging theme "A constant struggle to receive mental health care for mental disorders" embraced a number of barriers and few facilitators at individual, family, community and structural levels that people faced when seeking mental health care services. Identified barriers people needed to overcome were: Poverty and lack of family support, Fear of stigmatization, Poor community awareness of mental disorders, Societal beliefs in traditional healers and prayers, Scarce resources in mental health care and Gender imbalance in care seeking behavior. The few facilitators to receive mental health care were: Collaboration between authorities and organizations in mental health and having a Family with awareness of mental disorders and health insurance. CONCLUSION: From a public health perspective, this study revealed important findings of the numerous barriers and the few facilitating factors available to people seeking health for mental disorders. Having a supportive family with awareness of mental disorders who also were equipped with a health insurance was perceived as vital for successful treatment. This study highlights the need of improving availability, accessibility, acceptability and quality of mental health care at all levels in order to improve mental health care among Rwandans affected by mental disorders. PMID- 26672597 TI - MECP2 duplication syndrome in a Chinese family. AB - BACKGROUND: Methyl-CpG-binding protein 2 (MeCP2) is a key transcriptional regulator of gene expression in the maintenance and development of the central nervous system. Loss- or gain-function of this gene may contribute to neurodevelopmental disorders. The aim of this study is to delineate the clinical characteristics of MECP2 duplication syndrome and the hereditary mechanism in a Chinese family. CASE PRESENTATION: We identified a Chinese family with three persons carry MECP2 gene duplication: a boy, his mother and his grandmother. The duplication segment which was detected by multiplex ligation-dependent probe amplification (MLPA) included gene MECP2, interleukin-1 receptor-associated kinase 1 (IRAK1), filamin A (FLNA), and L1 cell adhesion molecule (L1CAM). Furthermore, array comparative genomic hybridization (aCGH) was performed on the mother, showed that MECP2 containing duplication was 510 Kb (153,113,885 153,624,154), including 16 other genes except MECP2. The boy showed most symptoms of MECP2 duplication syndrome. His mother and maternal grandmother were asymptomatic. Both female carriers had a skewed X chromosome inactivation (XCI), which were 80:20 and 74:26 respectively. CONCLUSION: To our knowledge, this is the second reported Chinese Han family with MECP2-containing duplications. And this patient had recurrent respiratory infections which was different from the first two Chinese-brother cases. MECP2 is the core gene responsible for MECP2 duplication syndrome. XCI may play an important role in modulating the clinical manifestation. PMID- 26672598 TI - A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI]. AB - BACKGROUND: Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI) requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure ('door-to end') time and baseline platelet activity on platelet inhibition within 24hours post-STEMI. METHODS AND FINDINGS: 108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate(r) platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE), bleeding and stent thrombosis (ST) were recorded. Baseline ADP activity was high (88.3U [71.8-109.0]), procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40-70] and infusion duration 30minutes [20-42]). Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U) was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%). Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre procedural morphine use was associated with significantly higher ADP activity following intervention. CONCLUSIONS: Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity. PMID- 26672600 TI - HIV Vaccination, is Breakthrough Underway? AB - After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis. PMID- 26672599 TI - Electricity and Water Conservation on College and University Campuses in Response to National Competitions among Dormitories: Quantifying Relationships between Behavior, Conservation Strategies and Psychological Metrics. AB - "Campus Conservation Nationals" (CCN) is a recurring, nation-wide electricity and water-use reduction competition among dormitories on college campuses. We conducted a two year empirical study of the competition's effects on resource consumption and the relationship between conservation, use of web technology and various psychological measures. Significant reductions in electricity and water use occurred during the two CCN competitions examined (n = 105,000 and 197,000 participating dorm residents respectively). In 2010, overall reductions during the competition were 4% for electricity and 6% for water. The top 10% of dorms achieved 28% and 36% reductions in electricity and water respectively. Participation was larger in 2012 and reductions were slightly smaller (i.e. 3% electricity). The fact that no seasonal pattern in electricity use was evident during non-competition periods suggests that results are attributable to the competition. Post competition resource use data collected in 2012 indicates that conservation behavior was sustained beyond the competition. Surveys were used to assess psychological and behavioral responses (n = 2,900 and 2,600 in 2010 and 2012 respectively). Electricity reductions were significantly correlated with: web visitation, specific conservation behaviors, awareness of the competition, motivation and sense of empowerment. However, participants were significantly more motivated than empowered. Perceived benefits of conservation were skewed towards global and future concerns while perceived barriers tended to be local. Results also suggest that competitions may be useful for "preaching beyond the choir"-engaging those who might lack prior intrinsic or political motivation. Although college life is distinct, certain conclusions related to competitions, self-efficacy, and motivation and social norms likely extend to other residential settings. PMID- 26672601 TI - Impact of Telaprevir in HCV Patients with Cirrhosis and RVR: Real-Life Data from Boceprevir or Telaprevir based "Triple Therapy" Experience in Southern Italy. AB - : Background and Rationale of Study: The real-life data of triple therapy-based treatment in patients with chronic hepatitis C were investigated in this survey of 12 clinical centers of southern Italy. This retrospective study analyzed data from 176 consecutive patients. METHODS: 125 (70%) patients were treated with telaprevir, and 51(30%) with boceprevir. There were no differences in demographic characteristics between the groups. The degree of Liver Fibrosis (LF) was evaluated according to Liver Biopsy (LB) and/or Transient Elastography (TE). 53/176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were treatment naive, and the remaining were not: 92 were non-responders (52, 84%), 63 relapsed (35,79%), and 5 discontinued treatment (2, 8%). RESULTS: Overall, the rapid Virological Response (RVR) rate was 67.6%. Of the 103 patients who had follow-up for at least 12 weeks after the end of treatment, 61 (59, 2%) achieved a Sustained Virological Response (SVR). According to multivariate analysis for SVR, RVR was the only independent predictive factor of SVR, irrespective of the degree of LF and the type of response to previous treatments. In telaprevir-treated patients, the rate of RVR was similar in patients with F0-F2, F3 and F4 fibrosis (85%, 84%, 78%, respectively), and the SVR rates among RVR patients was similar irrespective of LF. CONCLUSIONS: Data from this real-life study confirm the efficacy reported in clinical trials, although cirrhosis appears to play a smaller role in influencing treatment efficacy. Moreover, RVR is the only independent predictive factor of response regardless of cirrhosis. Based on RVR and for patients with cirrhosis, a shorter therapy might be considered, at least with telaprevir-based therapy. PMID- 26672602 TI - Correction: Targeting Vascular Endothelial Growth Factor Receptor 2 and Protein Kinase D1 Related Pathways by a Multiple Kinase Inhibitor in Angiogenesis and Inflammation Related Processes In Vitro. PMID- 26672603 TI - Combination of tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species. AB - Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24-72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/ time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells. PMID- 26672605 TI - Correction: Identification of a Male-Produced Pheromone Component of the Citrus Longhorned Beetle, Anoplophora chinensis. PMID- 26672604 TI - Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Recently, using the patient's genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration's tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause. RESULTS: A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to 2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage. CONCLUSIONS: The use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens. TRIAL REGISTRATION PROSPERO: Database registration: CRD42015024127. PMID- 26672606 TI - A New mHealth application to support treatment of sleep apnoea patients. AB - Introduction Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep apnoea (OSA), but adherence is frequently suboptimal. Innovative, patient-centred interventions are, therefore, needed to enhance compliance. Due to its low cost and ubiquity, mobile health (mHealth) technology seems particularly suited for this purpose. We endeavoured to develop an mHealth application called "APPnea," aimed at promoting patient self monitoring of CPAP treatment. We then assessed the feasibility and acceptability of APPnea in a group of OSA patients. Methods Consecutive OSA patients used APPnea for six weeks. APPnea gave patients daily reminders to answer three questions about their OSA treatment (CPAP use, physical activity, and diet) and prompted them to upload their body weight weekly. Answers were saved to a secure server for further analysis. After completing the study, patients gave their anonymous opinions about APPnea. Results We enrolled 60 patients with OSA receiving CPAP treatment. The mean age was 56 +/- 10 years and the apnoea hypopnea index was 47 +/- 25 events/hour. In total, 63% of participants completed the daily questionnaire for more than 66% of the study period. Objective CPAP compliance was generally high (5.3 +/- 1.6 hours/night). In a subset of 38 patients naive to CPAP, those who used APPnea regularly had significantly higher CPAP compliance. Satisfaction levels were high for the majority of users. Conclusion This mHealth intervention is not only feasible but also satisfactory to patients. Although larger randomized trials and cost-effectiveness studies should be performed, this study shows that APPnea could promote participation and improve compliance among patients with OSA, thereby improving outcomes. PMID- 26672607 TI - Neutrophil Elastase-Generated Fragment of Vascular Endothelial Growth Factor-A Stimulates Macrophage and Endothelial Progenitor Cell Migration. AB - Elastase released from neutrophils as part of the innate immune system has been implicated in chronic diseases such as emphysema and cardiovascular disease. We have previously shown that neutrophil elastase targets vascular endothelial growth factor-A (VEGF) for partial degradation to generate a fragment of VEGF (VEGFf) that has distinct activities. Namely, VEGFf binds to VEGF receptor 1 but not to VEGF receptor 2 and shows altered signaling compared to intact VEGF. In the present study we investigated the chemotactic function of VEGF and VEGFf released from cells by neutrophil elastase. We found that endothelial cells migrated in response to intact VEGF but not VEGFf whereas RAW 264.7 macrophages/monocytes and embryonic endothelial progenitor cells were stimulated to migrate by either VEGF or VEGFf. To investigate the role of elastase-mediated release of VEGF from cells/extracellular matrices, a co-culture system was established. High or low VEGF producing cells were co-cultured with macrophages, endothelial or endothelial progenitor cells and treated with neutrophil elastase. Elastase treatment stimulated macrophage and endothelial progenitor cell migration with the response being greater with the high VEGF expressing cells. However, elastase treatment led to decreased endothelial cell migration due to VEGF cleavage to VEGF fragment. These findings suggest that the tissue response to NE-mediated injury might involve the generation of diffusible VEGF fragments that stimulate inflammatory cell recruitment. PMID- 26672608 TI - Prevention and Treatment of Anemia in Infants through Supplementation, Assessing the Effectiveness of Using Iron Once or Twice Weekly. AB - BACKGROUND: The objective of this study was to compare the effect of once weekly iron supplementation (IS) versus twice weekly, on hemoglobin (Hb) levels and anemia prevalence. METHODS: In this cluster-randomized clinical trial study, we evaluated infants aged 6-18 months. Length of intervention: 16 weeks. Infants were cluster randomized to either 25 mg elemental iron once weekly (Group-A) or twice weekly (Group-B). Primary outcome variables were change in Hb concentration and anemia prevalence. Two biochemical evaluations were performed to determine Hb concentrations, before and after intervention. RESULTS: For Group-A, at baseline, mean Hb concentration was 10.8 +/- 1.18 g/dl and after intervention 11.2 +/- 1.07 g/dl,p = 0.12; anemia prevalence was 52.5% at baseline and 37.5% after intervention,p = 0.18; Group-B, mean baseline Hb was 10.7 +/- 1.04 g/dl, and 11.3 +/- 0.91 g/dl after intervention,p = 0.002; anemia prevalence reduced from 57.9 to 36.8%. CONCLUSIONS: Both once and twice weekly IS increased mean Hb concentration; however, twice weekly supplementation provided more significant results. PMID- 26672609 TI - Tooth loss is independently associated with poor outcomes in stable coronary heart disease. AB - OBJECTIVE: We investigated associations between self-reported tooth loss and cardiovascular outcomes in a global stable coronary heart disease cohort. METHODS: We examined 15,456 patients from 39 countries with stable coronary heart disease (prior myocardial infarction, prior revascularisation or multivessel coronary heart disease) in the STABILITY trial. At baseline, patients reported number of teeth (26-32 (all), 20-25, 15-19, 1-14 and no teeth) and were followed for 3.7 years. Cox regression models adjusted for cardiovascular risk factors and socioeconomic status, determined associations between tooth loss level (26-32 teeth: lowest level; no teeth: highest level) and cardiovascular outcomes. RESULTS: After adjustment, every increase in tooth loss level was associated with an increased risk of the primary outcome, the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (hazard ratio 1.06; 95% confidence interval 1.02-1.10), cardiovascular death (1.17; 1.10-1.24), all-cause death (1.16; 1.11-1.22) and non-fatal or fatal stroke (1.14; 1.04-1.24), but not with non-fatal or fatal myocardial infarction (0.99; 0.94-1.05). Having no teeth, compared to 26-32 teeth, entailed a significantly higher risk of the primary outcome (1.27 (1.08, 1.49)), cardiovascular death (1.85 (1.45, 2.37), all-cause death (1.81 (1.50, 2.20)) and stroke (1.67 (1.15, 2.39)). CONCLUSIONS: In this large global cohort of patients with coronary heart disease, self-reported tooth loss predicted adverse cardiovascular outcomes and all-cause death independent of cardiovascular risk factors and socioeconomic status. PMID- 26672610 TI - Quantitative Analyses of the Projection of Individual Neurons from the Midline Thalamic Nuclei to the Striosome and Matrix Compartments of the Rat Striatum. AB - A fundamental organizing principle of the striatum is the striosome/matrix system that is defined by inputs/outputs and neurochemical markers. The thalamostriatal projection is highly heterogeneous originating in many subnuclei of the thalamus including the midline (ML) and intralaminar (IL) nuclei. We examined the dendritic morphology and axonal trajectory of 15 ML and 11 IL neurons by single neuron labeling with viral vectors in combination with mu-opioid receptor immunostaining in rat brains. Dendritic and axonal morphology defined ML neurons as type II cells consisting of at least two subclasses according to the presence or absence of striatal axon collaterals. In the striatum, ML neurons preferentially innervated striosomes, whereas parafascicular neurons preferentially innervated the matrix. Almost all single thalamostriatal neurons favoring striosome or matrix compartments also innervated the cerebral cortical areas that supplied cortical input to the same striatal compartment. We thus revealed that thalamostriatal projections are highly organized 1) by the similarity in morphological characteristics and 2) their preference for the striatal compartments and cortical areas. These findings demonstrate that the functional properties of striatal compartments are influenced by both their cortical and thalamic afferents presumably with a different time latency and support selective dynamics for the striosome and matrix compartments. PMID- 26672611 TI - "Mind boggling" variation in hospital prices is seen across US. PMID- 26672612 TI - The Redox-sensitive Induction of the Local Angiotensin System Promotes Both Premature and Replicative Endothelial Senescence: Preventive Effect of a Standardized Crataegus Extract. AB - Endothelial senescence, characterized by an irreversible cell cycle arrest, oxidative stress, and downregulation of endothelial nitric oxide synthase (eNOS), has been shown to promote endothelial dysfunction leading to the development of age-related vascular disorders. This study has assessed the possibility that the local angiotensin system promotes endothelial senescence in coronary artery endothelial cells and also the protective effect of the Crataegus extract WS1442, a quantified hawthorn extract. Serial passaging from P1 to P4 (replicative senescence) and treatment of P1 endothelial cells with the eNOS inhibitor L-NAME (premature senescence) promoted acquisition of markers of senescence, enhanced ROS formation, decreased eNOS expression, and upregulation of angiotensin converting enzyme (ACE) and AT1 receptors. Increased SA-beta-gal activity and the upregulation of ACE and AT1R in senescent cells were prevented by antioxidants, an ACE inhibitor, and by an AT1 receptor blocker. WS1442 prevented SA-beta-gal activity, the downregulation of eNOS, and oxidative stress in P3 cells. These findings indicate that the impairment of eNOS-derived nitric oxide formation favors a pro-oxidant response triggering the local angiotensin system, which, in turn, promotes endothelial senescence. Such a sequence of events can be effectively inhibited by a standardized polyphenol-rich extract mainly by targeting the oxidative stress. PMID- 26672613 TI - Living Well After 80 Years: An Introduction to the Special Issue. PMID- 26672614 TI - Conserved and unique features of the homeologous maize Aux/IAA proteins ROOTLESS WITH UNDETECTABLE MERISTEM 1 and RUM1-like 1. AB - The maize (Zea mays L.) Aux/IAA protein RUM1 (ROOTLESS WITH UNDETECTABLE MERISTEM 1) is a key regulator of lateral and seminal root formation. An ancient maize genome duplication resulted in the emergence of its homeolog rum1-like1 (rul1), which displays 92% amino acid sequence identity with RUM1. Both, RUL1 and RUM1 exhibit the canonical four domain structure of Aux/IAA proteins. Moreover, both are localized to the nucleus, are instable and have similar short half-lives of ~23min. Moreover, RUL1 and RUM1 can be stabilized by specific mutations in the five amino acid degron sequence of domain II. In addition, proteins encoded by both genes interact in vivo with auxin response factors (ARFs) such as ZmARF25 and ZmARF34 in protoplasts. Although it was demonstrated that RUL1 and RUM1 can homo and heterodimerize in vivo, rul1 expression is independent of rum1. Moreover, on average rul1 expression is ~84-fold higher than rum1 in the 12 tested tissues and developmental stages, although the relative expression levels in different root tissues are very similar. While RUM1 and RUL1 display conserved biochemical properties, yeast-two-hybrid in combination with BiFC experiments identified a RUM1-associated protein 1 (RAP1) that specifically interacts with RUM1 but not with RUL1. This suggests that RUM1 and RUL1 are at least in part interwoven into different molecular networks. PMID- 26672615 TI - Hormone crosstalk in wound stress response: wound-inducible amidohydrolases can simultaneously regulate jasmonate and auxin homeostasis in Arabidopsis thaliana. AB - Jasmonate (JA) and auxin are essential hormones in plant development and stress responses. While the two govern distinct physiological processes, their signaling pathways interact at various levels. Recently, members of the Arabidopsis indole 3-acetic acid (IAA) amidohydrolase (IAH) family were reported to metabolize jasmonoyl-isoleucine (JA-Ile), a bioactive form of JA. Here, we characterized three IAH members, ILR1, ILL6, and IAR3, for their function in JA and IAA metabolism and signaling. Expression of all three genes in leaves was up regulated by wounding or JA, but not by IAA. Purified recombinant proteins showed overlapping but distinct substrate specificities for diverse amino acid conjugates of JA and IAA. Perturbed patterns of the endogenous JA profile in plants overexpressing or knocked-out for the three genes were consistent with ILL6 and IAR3, but not ILR1, being the JA amidohydrolases. Increased turnover of JA-Ile in the ILL6- and IAR3-overexpressing plants created symptoms of JA deficiency whereas increased free IAA by overexpression of ILR1 and IAR3 made plants hypersensitive to exogenous IAA conjugates. Surprisingly, ILL6 overexpression rendered plants highly resistant to exogenous IAA conjugates, indicating its interference with IAA conjugate hydrolysis. Fluorescent protein tagged IAR3 and ILL6 co-localized with the endoplasmic reticulum-localized JA-Ile 12-hydroxylase, CYP94B3. Together, these results demonstrate that in wounded leaves JA-inducible amidohydrolases contribute to regulate active IAA and JA-Ile levels, promoting auxin signaling while attenuating JA signaling. This mechanism represents an example of a metabolic-level crosstalk between the auxin and JA signaling pathways. PMID- 26672617 TI - A new model of an arteriovenous fistula in chronic kidney disease in the mouse: beneficial effects of upregulated heme oxygenase-1. AB - The arteriovenous fistula (AVF) is the preferred hemodialysis vascular access, but it is complicated by high failure rates and attendant morbidity. This study provides the first description of a murine AVF model that recapitulates two salient features of hemodialysis AVFs, namely, anastomosis of end-vein to side artery to create the AVF and the presence of chronic kidney disease (CKD). CKD reduced AVF blood flow, observed as early as 3 days after AVF creation, and increased neointimal hyperplasia, venous wall thickness, thrombus formation, and vasculopathic gene expression in the AVF. These adverse effects of CKD could not be ascribed to preexisting alterations in blood pressure or vascular reactivity in this CKD model. In addition to vasculopathic genes, CKD induced potentially vasoprotective genes in the AVF such as heme oxygenase-1 (HO-1) and HO-2. To determine whether prior HO-1 upregulation may protect in this model, we upregulated HO-1 by adeno-associated viral gene delivery, achieving marked venous induction of the HO-1 protein and HO activity. Such HO-1 upregulation improved AVF blood flow and decreased venous wall thickness in the AVF. Finally, we demonstrate that the administration of carbon monoxide, a product of HO, acutely increased AVF blood flow. This study thus demonstrates: 1) the feasibility of a clinically relevant murine AVF model created in the presence of CKD and involving an end-vein to side-artery anastomosis; 2) the exacerbatory effect of CKD on clinically relevant features of this model; and 3) the beneficial effects in this model conferred by HO-1 upregulation by adeno-associated viral gene delivery. PMID- 26672616 TI - Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney. AB - Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1alpha (IRE1alpha), phosphorylated eukaryotic initiation factor-alpha (eIF2alpha), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1alpha, p-eIF2alpha, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. PMID- 26672619 TI - Esterification of Ginsenoside Rh2 Enhanced Its Cellular Uptake and Antitumor Activity in Human HepG2 Cells. AB - Our previous research had indicated that the octyl ester derivative of ginsenoside Rh2 (Rh2-O) might have a higher bioavailability than Rh2 in the Caco 2 cell line. The aim of this study was to investigate the cellular uptake and antitumor effects of Rh2-O in human HepG2 cells as well as its underlying mechanism compared with Rh2. Results showed that Rh2-O exhibited a higher cellular uptake (63.24%) than Rh2 (36.76%) when incubated with HepG2 cells for 24 h. Rh2-O possessed a dose- and time-dependent inhibitory effect against the proliferation of HepG2 cells. The IC50 value of Rh2-O for inhibition of HepG2 cell proliferation was 20.15 MUM, which was roughly half the value of Rh2. Rh2-O induced apoptosis of HepG2 cells through a mitochondrial-mediated intrinsic pathway. In addition, the accumulation of ROS was detected in Rh2-O-treated HepG2 cells, which participated in the apoptosis of HepG2 cells. Conclusively, the findings above all suggested that Rh2-O as well as Rh2 inducing HepG2 cells apoptosis might involve similar mechanisms; however, Rh2-O had better antitumor activities than Rh2, probably due to its higher cellular uptake. PMID- 26672618 TI - Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury. AB - Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. The beneficial effects of HO-1 expression are not merely due to degradation of the pro-oxidant heme but are also credited to the by-products that have potent, protective effects, including antioxidant, anti-inflammatory, and prosurvival properties. This is well reflected in the preclinical animal models of injury in both renal and nonrenal settings. However, excessive accumulation of the by-products can be deleterious and lead to mitochondrial toxicity and oxidative stress. Therefore, use of the HO system in alleviating injury merits a targeted approach. Based on the higher susceptibility of the proximal tubule segment of the nephron to injury, we generated transgenic mice using cre-lox technology to enable manipulation of HO-1 (deletion or overexpression) in a cell-specific manner. We demonstrate the validity and feasibility of these mice by breeding them with proximal tubule specific Cre transgenic mice. Similar to previous reports using chemical modulators and global transgenic mice, we demonstrate that whereas deletion of HO 1, specifically in the proximal tubules, aggravates structural and functional damage during cisplatin nephrotoxicity, selective overexpression of HO-1 in proximal tubules is protective. At the cellular level, cleaved caspase-3 expression, a marker of apoptosis, and p38 signaling were modulated by HO-1. Use of these transgenic mice will aid in the evaluation of the effects of cell specific HO-1 expression in response to injury and assist in the generation of targeted approaches that will enhance recovery with reduced, unwarranted adverse effects. PMID- 26672620 TI - CORM-EDE1: A Highly Water-Soluble and Nontoxic Manganese-Based photoCORM with a Biogenic Ligand Sphere. AB - [Mn(CO)5Br] reacts with cysteamine and 4-amino-thiophenyl with a ratio of 2:3 in refluxing tetrahydrofuran to the complexes of the type [{(OC)3Mn}2(MU SCH2CH2NH3)3]Br2 (1, CORM-EDE1) and [{(OC)3Mn}2(MU-SC6H4-4-NH3)3]Br2 (2, CORM EDE2). Compound 2 precipitates during refluxing of the tetrahydrofuran solution as a yellow solid whereas 1 forms a red oil that slowly solidifies. Recrystallization of 2 from water yields the HBr-free complex [{(OC)3Mn}2(MU-S C6H4-4-NH2)2(MU-SC6H4-4-NH3)] (3). The n-propylthiolate ligand (which is isoelectronic to the bridging thiolate of 1) leads to the formation of the di- and tetranuclear complexes [(OC)4Mn(MU-S-nPr)2]2 and [(OC)3Mn(MU-S-nPr)]4. CORM EDE1 possesses ideal properties to administer carbon monoxide to biological and medicinal tissues upon irradiation (photoCORM). Isolated crystalline CORM-EDE1 can be handled at ambient and aerobic conditions. This complex is nontoxic, highly soluble in water, and indefinitely stable therein in the absence of air and phosphate buffer. CORM-EDE1 is stable as frozen stock in aqueous solution without any limitations, and these stock solutions maintain their CO release properties. The reducing dithionite does not interact with CORM-EDE1, and therefore, the myoglobin assay represents a valuable tool to study the release kinetics of this photoCORM. After CO liberation, the formation of MnHPO4 in aqueous buffer solution can be verified. PMID- 26672621 TI - Optical Rotation from Coupled Cluster and Density Functional Theory: The Role of Basis Set Convergence. AB - We have calculated the electronic optical rotation of seven molecules using coupled cluster singles-doubles (CCSD) and the second-order approximation (CC2) employing the aug-cc-pVXZ (X = D, T, or Q) basis sets. We have also compared to time-dependent density functional theory (TDDFT) by utilizing two functionals B3LYP and CAM-B3LYP and the same basis sets. Using relative and absolute error schemes, our calculations demonstrate that the CAM-B3LYP functional predicts optical rotation with the minimum deviations compared to CCSD at lambda = 355 and 589.3 nm. Furthermore, our results illustrate that the aug-cc-pVDZ basis set provides the optical rotation in good agreement with the larger basis sets for molecules not possessing small-angle optical rotation at lambda = 589.3 nm. We have also performed several two-point inverse power extrapolations for the basis set convergence, i.e., OR(infinity) + AX(-n), using the CC2 model at lambda = 355 and 589.3 nm. Our results reveal that a two-point inverse power extrapolation with the aug-cc-pVTZ and aug-cc-pVQZ basis sets at n = 5 provides optical rotation deviations similar to those of aug-cc-pV5Z with respect to the basis limit. PMID- 26672622 TI - Ultrasound of selected pathologies of the small intestine. AB - Intestines, especially the small bowel, are rarely subject to US assessment due to the presence of gases and chyme. The aim of this paper was to analyze ultrasound images in selected pathologies of the small intestine in adults, including the aspects of differential diagnosis. MATERIAL AND METHODS: In 2001 2012, abdominal ultrasound examinations were conducted in 176 patients with the following small bowel diseases: Crohn's disease (n=35), small bowel obstruction (n=35), yersiniosis (n=28), infectious diarrhea (n=26), bacterial overgrowth syndrome (n=25), coeliac disease (n=15) and small bowel ischemia (n=12). During examinations patients were fasting and no other particular preparations were needed. Convex transducers of 3.5-6 MHz and linear ones of 7-12 MHz were used. The assessment of the small intestine in four abdominal quadrants constituted an integral element of the examination. The following features of the small bowel ultrasound presentation were subject to analysis: thickness and perfusion of the walls, presence of thickened folds in the jejunum, reduction of their number, presence of fluid and gas contents in the intestine, its peristaltic activity, jejunization of the ileum and enteroenteric intussusception. Furthermore, the size of the mesenteric lymph nodes and the width of the superior mesenteric artery were determined and the peritoneal cavity was evaluated in terms of the presence of free fluid. RESULTS: Statistically significant differences were obtained between the thickness of the small intestine in Crohn's disease or in ischemic conditions and the thickness in the remaining analyzed pathological entities. Small bowel obstruction was manifested by the presence of distended loops due to gas and fluid as well as by severe peristaltic contractions occurring periodically. In the course of ischemic disease, the intestinal walls were thickened without the signs of increased perfusion and in the majority of cases intestinal stenosis was observed. Fluid in the intestine was detected in all patients with coeliac disease, gas in 86.7% of patients, thickening of the folds in the jejunum in 86.7%, their reduction in 80%, increased (enhanced) peristalsis in 93.3% and jejunization in 40%. In 80% of coeliac disease cases, the intestine showed the features of hyperemia on color Doppler examination and in 53.3% of patients the dilated lumen of the superior mesenteric artery was detected. Enlarged mesenteric lymph nodes were visualized in 73.3% of the subjects, enteroenteric intussusception in 33.3% and free fluid in the peritoneal cavity in 60%. CONCLUSIONS: Small bowel obstruction is manifested by the presence of evidently dilated intestinal loops filled with gas and fluid and periodical severe deepened peristalsis.Ischemic changes and Crohn's disease are characterized by the presence of fragmentarily thickened intestinal walls and intestinal stenosis. Moreover, in Crohn's disease, increased wall perfusion and mesenteric adenomegaly is encountered.Coeliac disease is manifested by: increased amount of fluid mainly in the jejunum, thickened and hyperemic jejunal walls, increased peristalsis;hypertrophied mucosal folds - often their number is reduced, jejunization and transient enteroenteric intussusception;ultrasound changes that require the differentiation with small intestinal bacterial overgrowth syndrome and, to a lesser degree, with infectious diarrhea. PMID- 26672623 TI - Elastic Properties of Protein Functionalized Nanoporous Polymer Films. AB - Retaining the conformational structure and bioactivity of immobilized proteins is important for biosensor designs and drug delivery systems. Confined environments often lead to changes in conformation and functions of proteins. In this study, lysozyme is chemically tethered into nanopores of polystyrene thin films, and submicron pores in poly(methyl methacrylate) films are functionalized with streptavidin. Nanoindentation experiments show that stiffness of streptavidin increases with decreasing submicron pore sizes. Lysozymes in polystyrene nanopores are found to behave stiffer than the submicron pore sizes and still retain their specific bioactivity relative to the proteins on flat surfaces. Our results show that protein functionalized ordered nanoporous polystyrene/poly(methyl methacrylate) films present heterogeneous elasticity and can be used to study interactions between free proteins and designed surfaces. PMID- 26672624 TI - Detection of Japanese eel endothelial cells-infecting virus in Anguilla japonica elvers. AB - Japanese eel endothelial cells-infecting virus (JEECV) has spread in eel farms and caused serious economic loss. In this study, we examined the prevalence of JEECV infection in 100 wild Japanese eel (Anguilla japonica) elvers caught from Yamaguchi prefecture, Japan, using quantitative PCR and conventional PCR. Total genomic DNA was obtained from the cranial quarter of the body in 70 of 100 eels and from the gill in the remaining. Of 30 gill samples, 20 were analyzed after pooling with other samples, and the remaining 10 were analyzed separately. A single positive result for JEECV was detected following analysis of the 10 separately analyzed samples. This result constitutes the first report of JEECV infection in wild A. japonica elvers. PMID- 26672625 TI - Solvent Vapor Growth of Axial Heterostructure Nanowires with Multiple Alternating Segments of Silicon and Germanium. AB - Herein, we report the formation of multisegment Si-Ge axial heterostructure nanowires in a wet chemical synthetic approach. These nanowires are grown by the liquid injection of the respective silicon and germanium precursors into the vapor phase of an organic solvent in which a tin-coated stainless steel substrate is placed. The Si-Ge transition is obtained by sequential injection with the more difficult Ge-Si transition enabled by inclusion of a quench sequence in the reaction. This approach allows for alternating between pure Si and pure Ge segments along the entire nanowire length with good control of the respective segment dimensions. The multisegment heterostructure nanowires presented are Ge Si, Si-Ge-Si, Ge-Si-Ge, Si-Ge-Si-Ge, and Si-Ge-Si-Ge-Si-Ge. The interfacial abruptness of the Ge to Si interface is also determined through the use of aberration corrected scanning transmission electron microscopy and electron energy loss spectroscopy. PMID- 26672626 TI - Enhanced Lithiation Cycle Stability of ALD-Coated Confined a-Si Microstructures Determined Using In Situ AFM. AB - Microfabricated amorphous silicon (a-Si) pits ~4 MUm in diameter and 100 nm thick were fabricated to be partially confined in a nickel (Ni) current collector. Corresponding unconfined pillars were also fabricated. The samples were coated with 1.5, 3, or 6 nm of Al2O3 ALD. These samples were tested in electrolytes of 3:7 by weight ethylene carbonate:ethyl methyl carbonate (EC:EMC) with 1.2 M LiPF6 salt with and without 2% fluoroethylene carbonate (FEC) and in a pure FEC electrolyte with 10 wt % LiPF6. The samples were imaged with an atomic force microscope during electrochemical cycling to evaluate morphology evolution and solid electrolyte interphase (SEI) formation. The partially confined a-Si structures had superior cycle efficiency relative to the unconfined a-Si pillars. Additionally, samples with 3 nm of ALD achieved higher charge capacity and enhanced cycle life compared to samples without ALD, demonstrated thinner SEI formation, and after 10 cycles at a 1 C rate remained mostly intact and had actually decreased in diameter. Finally, the samples with 3 nm of ALD had better capacity retention in the baseline 3:7 EC:EMC than in either of the FEC containing electrolytes. PMID- 26672627 TI - Variation in Lipid Profile Across Different Patterns of Obesity - Observations from Guwahati, Assam. AB - BACKGROUND: Obesity adversely affects cardiovascular health is known. But, data is few in this regard from Assam, northeast India. The serum lipid profile is performed for cardio-metabolic status assessment. AIM: The aim of the study was to investigate variation in serum lipids across different obesity patterns in an urban population from Assam. MATERIALS AND METHODS: Two hundred subjects were classified by WC (waist circumference) and BMI (body mass index) values into four groups as follows: Group I (normal WC, normal BMI), Group II (normal WC, increased BMI), Group III (increased WC, normal BMI) and Group IV (increased WC, increased BMI). WC and BMI served as measures of central and generalized obesity respectively. Lipid profile was measured using VITROS 5600 Autoanalyser, and compared across these groups. Multivariate analyses were performed separately for males and females to confirm the results of univariate analyses. RESULTS: WC and BMI exhibited significant correlations with different lipid parameters. Group IV individuals had the most abnormal lipid profile values, while, Group I individuals had the most normal values. Group II and Group III individuals had intermediate values. BMI was independently associated with serum triglycerides in both males and females. WC was independently associated with high density lipoprotein cholesterol in females. CONCLUSION: The lipid values varied significantly across different obesity patterns. Serum lipid concentrations were strongly influenced by anthropometric indices of obesity in both sexes. Presence of both central and generalized obesity led to greater abnormalities in lipid profile than presence of central or generalized obesity alone. PMID- 26672628 TI - Errors made in the ultrasound diagnostics of the spleen. AB - Ultrasonography, like any imaging method, entails the risk of errors. From among all means of imaging, it is the most subjective and dependent on the examiner's knowledge and experience. This paper presents the causes of examiner-dependent errors as well as those which result from technical settings and preparation of the patient for the examination. Moreover, the authors discuss the most frequent errors in the diagnosis of splenic conditions, which result from insufficient knowledge concerning anatomical variants of this organ, wrong measurements and incorrect examination technique. The mistakes made in the differentiation of focal lesions of the spleen and its hilum are also discussed. Additionally, the differentiation of collateral circulation, lymph nodes and accessory spleens is mentioned. The authors also draw attention to erroneous interpretation of the left liver lobe as a fragment of the spleen as well as the prominent tail of the pancreas filled with gastric contents and intestinal loops as abnormal masses or fluid cisterns in the area of the splenic hilum. Furthermore, the pathologies of the hilum are discussed such as tumors of the splenic flexure of the colon, lesions arising from the left kidney or the left adrenal gland. The authors list characteristic imaging features of the most common focal lesions visualized in a standard ultrasound scan as well as enhancement patterns appearing in contrast enhanced examinations. The article discusses the features and differentiation of, among others, infarction, splenic cysts including hydatid ones, abscesses and angiomas. The ultrasound appearance of lymphoma and secondary involvement of the spleen by other malignant neoplasms is also mentioned. Moreover, the authors provide useful tips connected with imaging techniques and interpretation of the findings. The ultrasound examination carried out in compliance with current standards allows for an optimal assessment of the organ and reduction of the error-making risk. This article is based on the publication of the experts from the Polish Ultrasound Society of 2005 and updated with the latest findings in pertinent literature. The photographic documentation, which provides images of the discussed lesions, is attached to this article. PMID- 26672629 TI - Preclinical validation of automated dual-energy X-ray absorptiometry and computed tomography-based body composition measurements. AB - BACKGROUND: The aim of this study was to determine and validate a set of Hounsfield unit (HU) ranges to segment computed tomography (CT) images into tissue types and to test the validity of dual-energy X-ray absorptiometry (DXA) tissue segmentation on pure, unmixed porcine tissues. METHODS: This preclinical prospective study was approved by the local ethical committee. Different quantities of porcine bone tissue (BT), lean tissue (LT) and adipose tissue (AT) were scanned using DXA and CT. Tissue type segmentation in DXA was performed via the standard clinical protocol and in CT through different sets of HU ranges. Percent coefficients of variation (%CV) were used to assess precision while % differences of observed masses were tested against zero using the Wilcoxon signed rank Test. RESULTS: Total mass DXA measurements differ little but significantly (P=0.016) from true mass, while total mass CT measurements based on literature values show non-significant (P=0.69) differences of 1.7% and 2.0%. BT mass estimates with DXA differed more from true mass (median -78.2 to -75.8%) than other tissue types (median -11.3 to -8.1%). Tissue mass estimates with CT and literature HU ranges showed small differences from true mass for every tissue type (median -10.4 to 8.8%). CONCLUSION: The most suited method for automated tissue segmentation is CT and can become a valuable tool in quantitative nuclear medicine. PMID- 26672630 TI - [18F]FDG PET/CT for the assessment of the volume of the spleen. AB - BACKGROUND: The aim of this study was to report on the feasibility and accuracy of spleen volume determination on FDG PET/CT imaging using region growing and the CT part of the PET/CT examination as anatomical landmark (PET-CT based spleen volume method PBM) and volume summation of axial CT sections of the spleen as gold standard (true spleen volume (TSV). We also aimed to compare results obtained to the estimative methods (ESV). METHODS: Thirty-nine FDG PET/CT images taken from 32 patients (15 women, age range: 16-83 years) suffering from lymphoma, covering a wide range of spleen volumes based on visual CT assessment, in whom CT as well as FDG PET images revealed no focal spleen abnormalities were included for analysis. ESV1, ESV2 and PBM were determined on all examinations and compared to TSV. RESULTS: ESV1 volumes were significantly larger (median 668 cm3 [range: 121-4303 cm3] [P=0.0001]) and ESV2 volumes significantly smaller (median 424 cm3 [range: 84-2679 cm3] [P=0.0001]) when compared to TSV volumes (median 582 cm3 [range: 105-4847 cm3] which was not so for PBS volumes (median 540cm3 [range: 120-4560 cm3]). Time needed for TSV assessment (median: 17 min. [range: 6-65 min.]) was related to spleen volume (r=0.691 [P=0.0001]). The mean and standard deviation of the percentage spread (ESV1, ESV2, PBM-TSV/100%) around the mean (ESV1, ESV2, PBM+TSV/2) were respectively 18%+/-15.6% (ESV1 vs. TSV), -25%+/ 15.6% (ESV2 vs. TSV) and -2.8%+/-12.3% (PBM vs. TSV). Mean SUVmax of the spleen was 4.8 SUV (SD: 2.6 SUV), mean percentage cut-off for region growing was 7.3% (sd: 5.8%). Spleen volumes defined by PBM correlated with their corresponding SUVmax value (r=0.469 [P=0.03]). Time needed for PBM measurements was between 2-3 min in all patients. CONCLUSION: Spleen volumes may be rapidly and accurately derived from the FDG PET part of the PET/CT examination through region growing and by using the CT part of the PET/CT examination as anatomical landmark for contour delineation. As opposed to ESV1 and ESV2, the PBM method does not suffer from a systematic bias and shows a smaller variation against the mean percentage difference. Combining functional and morphological data for spleen volume assessment is time-saving. PMID- 26672631 TI - Comparative Fluorescence Resonance Energy-Transfer Study in Pluronic Triblock Copolymer Micelle and Niosome Composed of Biological Component Cholesterol: An Investigation of Effect of Cholesterol and Sucrose on the FRET Parameters. AB - The formation of pluronic triblock copolymer (F127)-cholesterol-based niosome and its interaction with sugar (sucrose) molecules have been investigated. The morphology of F127-cholesterol -based niosome in the presence of sucrose has been successfully demonstrated using dynamic light scattering (DLS) and transmission electron microscopic (TEM) techniques. The DLS profiles and TEM images clearly suggest that the size of the niosome aggregates increases significantly in the presence of sucrose. In addition to structural characterization, a detailed comparative fluorescence resonance energy transfer (FRET) study has been carried out in these F127-containing aggregates, involving coumarin 153 (C153) as donor (D) and rhodamine 6G (R6G) as an acceptor (A) to monitor the dynamic heterogeneity of the systems. Besides, time-resolved anisotropy and fluorescence correlation spectroscopy measurements have been carried out to monitor the rotational and lateral diffusion motion in these F127-cholesterol-based aggregates using C153 and R6G, respectively. During the course of FRET study, we have observed multiple time constants of FRET inside the F127-cholesterol-based niosomes in contrast with the F127 micelle. This corresponds to the presence of more than one preferential donor-acceptor (D-A) distance in niosomes than in F127 micelle. FRET has also been successfully used to probe the effect of sucrose on the morphology of F127-cholesterol-based niosome. In the presence of sucrose, the time constant of FRET further increases as the D-A distances increase in sucrose decorated niosome. Finally, the excitation-wavelength-dependent FRET studies have indicated that as the excitation of donor molecules varies from 408 to 440 nm the contribution of the faster rise component of the acceptor enhances considerably, which clearly establishes the dynamics heterogeneity of both systems. Our findings also indicate that FRET is completely intravesicular in nature in these block copolymer-cholesterol-based aggregates. PMID- 26672632 TI - A new look at acquired heart diseases in a contemporary sub-Saharan African pediatric population: the case of Yaounde, Cameroon. AB - BACKGROUND: Acquired heart diseases (AHD) in children cause significant morbidity and mortality especially in low resource settings. There is limited description of acquired childhood heart diseases in Cameroon, making it difficult to estimate its current contribution to childhood morbidity and mortality. Echocardiography is the main diagnostic modality in low resource settings and has a key role in the characterization and management of these disorders. We aimed to determine the prevalence and spectrum of AHD in children in Yaounde-Cameroon, in an era of echocardiography. These data are needed for health service and policy formulation. METHODS: Echocardiography records from August 2003 to December 2013 were reviewed. Echocardiography records of children <=18 years with an echocardiographic diagnosis of a definite AHD were identified and relevant data extracted from their records. RESULTS: One hundred and fifty eight children (13.4%) <=18 years had an AHD. The mean [+/- standard deviations (SD)] age was 11.9 (+/-4.4) years .The most common affected age group was 15-18 years (36.1%). Heart failure (20.3%), suspicion of rheumatic heart disease (RHD) (12.0%) and the presence of a heart murmur (8.9%) were the most common indications for echocardiography. RHD (41.1%), pericardial disease (25.3%), dilated cardiomyopathy (DCM) (15.8%) and endomyocardial fibrosis (EMF) (13.9%) were the most common AHD. Cor pulmonale was rare (1.3%). Fifty-seven (87.7%) children with RHD had mitral regurgitation alone or in combination with other heart valve lesions and 63.3% of the lesions were severe. CONCLUSIONS: RHD remains the most common AHD in children in this setting and is frequently severe. Multicenter collaborative studies will help to better describe the pattern of AHD and there should be a renewed focus on the prevention of RHD. PMID- 26672633 TI - Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours. AB - CONTEXT: As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage. OBJECTIVES: The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail. RESULTS: In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P < .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively. CONCLUSION: Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course. PMID- 26672634 TI - Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD. AB - CONTEXT: Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role. OBJECTIVE: The objective of the study was to determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a university hospital. PATIENTS: Patients were recruited from outpatient clinics or from the general population (n = 188). INTERVENTIONS: Measurement of hepatic triglyceride content by magnetic resonance spectroscopy, histology (liver biopsy), metabolic profile by means of an oral glucose tolerance test, and lipoprotein analyses were performed. OUTCOMES: Outcomes measured included standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, low-density lipoprotein (LDL) particle size/phenotype, and LDL/high density lipoprotein subfractions), and insulin resistance. RESULTS: Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared with patients without NAFLD. Despite small differences in triglycerides and high-density lipoprotein-cholesterol, patients with NAFLD had a significantly higher plasma apolipoprotein B to apolipoprotein A1 ratio (0.66 +/- 0.02 vs 0.58 +/- 0.02, P = .01) and smaller LDL particle size (216.2 +/- 0.7 vs 219.4 +/- 1.1 A, P = .01). Of note, these differences between patients with/without NAFLD were independent of the presence of obesity. Severity of steatohepatitis did not significantly influence the lipoprotein profile. Worse atherogenic dyslipidemia was best predicted by the degree of liver fat accumulation and adipose tissue and systemic insulin resistance. CONCLUSIONS: NAFLD was associated with a worse atherogenic lipoprotein profile, regardless of similar body mass index and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease (nonalcoholic steatohepatitis). PMID- 26672635 TI - Hypoglycemia in Diabetes Mellitus as a Coronary Artery Disease Risk Factor in Patients at Elevated Vascular Risk. AB - CONTEXT: Although clinical trials have shown that hypoglycemia is associated with coronary artery disease (CAD), little is known whether hypoglycemia is a CAD risk factor in primary care. OBJECTIVE: We sought to determine whether previous hypoglycemia was associated with incident CAD, and whether this association differed in patients of different underlying vascular risk. DESIGN, SETTING AND PARTICIPANTS: This is a longitudinal cohort study of diabetes patients without CAD before January 1, 2006 (n = 9173) followed at an academic network of 13 primary care practices from January 1, 2006 to June 30, 2012. Hypoglycemic events before January 1, 2006 were identified via International Classification of Diseases Ninth Revision codes from emergency department, inpatient and outpatient visits. MAIN OUTCOME MEASURE: Patients were followed until incident CAD or June 30, 2012. Cox regression with time interaction was used to determine the association between hypoglycemia and CAD (significance set at P <= .05). We then tested the association among high vascular risk patients (age >= 55 y, hemoglobin A1c >= 7.5%, >=2 risk factors [dyslipidemia, hypertension or obesity]), a subset of high vascular risk patients aged 65 years or older, and the remaining patients with lower vascular risk. RESULTS: Three percent of patients (n = 285) had previous hypoglycemia. Hypoglycemia was associated with a 2-fold CAD risk (hazard ratio [HR] 2.15; 95% confidence interval [95%CI] 1.24-3.74), adjusting for time interaction and vascular risk factors. Among high vascular risk patients, the risk was 3-fold (HR 3.01 [95%CI 1.15-7.91], n = 1823 [20% of cohort]), and over 4 fold (HR 4.62 [95%CI 1.65-12.9], n = 996) in the subset aged more than or equal to 65 years. No association was found in the remaining 80% of the cohort with lower vascular risk. CONCLUSIONS: Previous hypoglycemia was associated with CAD among high vascular risk patients. Hypoglycemia may not be a CAD risk factor for the majority of primary care patients with lower underlying vascular risk. PMID- 26672636 TI - Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes. AB - CONTEXT: People with type 1 diabetes (T1D) have markedly reduced insulin sensitivity (IS) compared to their nondiabetic counterparts, and reduced IS is linked to higher cardiovascular risk. OBJECTIVE: This study aimed to develop and validate an improved method for estimating IS in people with T1D. DESIGN: Prospective cohort. SETTING: Adults (36 with T1D, 41 nondiabetic) were recruited from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study for measurement of IS by hyperinsulinemic-euglycemic clamp to develop a clinically useful IS prediction equation (eIS) for T1D and nondiabetic individuals. These equations were then compared with previously published equations from the SEARCH and Pittsburgh Epidemiology of Diabetes Complications studies for the ability to predict measured IS in test sets of adults and adolescents from independent clamp studies. INTERVENTION: None. MAIN OUTCOME MEASURE: Comparison of clamp-measured IS to estimated IS. RESULTS: The best-fit prediction model (eIS) differed by diabetes status and included waist circumference, triglycerides, adiponectin, and diastolic blood pressure in all CACTI adults and insulin dose in adults with T1D (adjusted R(2) = 0.64) or fasting glucose and hemoglobin A1c (HbA1c) in nondiabetic adults (adjusted R(2) = 0.63). The eIS highly correlated with clamp measured IS in all of the non-CACTI comparison populations (r = 0.83, P = .0002 in T1D adults; r = 0.71, P = .01 in nondiabetic adults; r = 0.44, P = .008 in T1D adolescents; r = 0.44, P = .006 in nondiabetic adolescents). CONCLUSIONS: eIS performed better than previous equations for estimating IS in individuals with and without T1D. These equations could simplify point-of-care assessment of IS to identify patients who could benefit from targeted intervention. PMID- 26672638 TI - Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients. AB - CONTEXT: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonist treatment in type 2 diabetes (T2DM) reduce blood glucose and food intake. It has been suggested that these effects are partly mediated through central GLP-1 receptors (GLP-1Rs). The rodent and nonhuman primate hypothalamus show clear GLP-1R expression. However, a detailed description of GLP-1R expression in the human hypothalamus is lacking, and it is unknown whether this expression is altered in T2DM patients. OBJECTIVE: The objective of the study was to investigate the GLP 1R distribution in the human postmortem hypothalamus and to determine whether hypothalamic GLP-1R expression is altered in T2DM patients. DESIGN: We investigated the distribution of GLP-1R expression throughout the human hypothalamus by means of in situ hybridization. We also performed quantifications of GLP-1R mRNA expression in two hypothalamic nuclei (ie, the paraventricular nucleus [PVN] and infundibular nucleus [IFN]), comparing patients with T2DM and control subjects. RESULTS: We found that GLP-1R mRNA was expressed in a number of hypothalamic nuclei including the PVN and the IFN, both involved in the regulation of energy metabolism. We observed sporadic colocalization of the GLP 1R in the IFN with the orgexigenic neuropeptide Y, agouti-related peptide, or proopiomelanocortin transcripts. Comparison of GLP-1R mRNA in the PVN and IFN between T2DM patients and control subjects revealed a decreased expression in T2DM patients. CONCLUSIONS: Our studies show that GLP-1R is widely expressed throughout the human hypothalamus. The decreased expression of GLP-1R in the PVN and IFN of T2DM patients may be related to the dysregulation of feeding behavior and glucose homeostasis in T2DM. PMID- 26672637 TI - A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency. AB - CONTEXT: Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD). OBJECTIVES: To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months. DESIGN: Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens. SETTING: Twenty-five United States pediatric endocrinology centers. PATIENTS: Naive-to-treatment, prepubertal children with GHD (n = 68). INTERVENTION(S): Patients received single sc doses of somavaratan (0.8, 1.2, 1.8, 2.7, 4.0, or 6.0 mg/kg) during the 30-day dose finding phase, then were randomized to somavaratan 1.15 mg/kg weekly, 2.5 mg/kg twice monthly, or 5.0 mg/kg monthly for 6 months. MAIN OUTCOME MEASURES: Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV). RESULTS: Somavaratan pharmacokinetics was linearly proportional to dose; dose-dependent increases in the magnitude and duration of IGF-1 responses enabled weekly, twice monthly or monthly dosing. A single dose of somavaratan sustained IGF-1 responses for up to 1 month. No somavaratan or IGF-1 accumulation occurred with repeat dosing. Mean annualized HVs for somavaratan administered monthly, twice monthly, or weekly (7.86 +/- 2.5, 8.61 +/- 2.7, and 7.58 +/- 2.5 cm/y, respectively) were similar between groups. Adverse events were mostly mild and transient. CONCLUSIONS: Somavaratan demonstrated clinically meaningful improvements in HV and IGF-1 in prepubertal children with GHD, with no significant differences between monthly, twice-monthly, or weekly dosing. PMID- 26672640 TI - A Step Beyond Maternal Depression and Child Behavior Problems: The Role of Mother Child Aggression. AB - Previous researchers have identified problematic mother-child interaction patterns as a potential pathway through which maternal depressive symptoms impact child behavior problems, but could not establish the temporal precedence of these associations. This longitudinal study investigated mother-child aggression as a mechanism in the association between maternal depressive symptoms that occurred during infancy and subsequent child behavior problems among high-risk families. Two hundred thirty-four socioeconomically disadvantaged families were recruited from neighborhoods with high rates of family violence. During infancy (12-18 months), early childhood (4 years), and middle childhood (6 years), mothers reported their current depressive symptoms and use of psychological and physical aggression with their child. During early and middle childhood, mothers reported their children's behavior problems. Using path analyses, a temporal process was identified in which mother-child aggression during early childhood mediated the association between maternal depressive symptoms during infancy and higher levels of externalizing behavior problems during middle childhood. Mother--child aggression did not mediate the association between maternal depressive symptoms during infancy and higher levels of internalizing behavior problems during middle childhood. Early maternal depressive symptoms that occur during infancy are important risk factors for subsequent mother-child aggression, which, in turn, contributes to more child externalizing behavior problems. Therefore, screening mothers for depressive symptoms and providing intervention and prevention services to improve mother-child interactions may be crucial to preventing the exacerbation of externalizing behavior problems. Additional research is needed to identify pathways to child internalizing behavior problems. PMID- 26672639 TI - Body Mass Index and Risk of Nonalcoholic Fatty Liver Disease: Two Electronic Health Record Prospective Studies. AB - CONTEXT: The relationship between rising body mass index (BMI) and prospective risk of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is virtually absent. OBJECTIVE: Determine the extent of the association between BMI and risk of future NAFLD diagnosis, stratifying by sex and diabetes. DESIGN: Two prospective studies using Humedica and Health Improvement Network (THIN) with 1.54 and 4.96 years of follow-up, respectively. SETTING: Electronic health record databases. PARTICIPANTS: Patients with a recorded BMI measurement between 15 and 60 kg/m(2), and smoking status, and 1 year of active status before baseline BMI. Patients with a diagnosis or history of chronic diseases were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Recorded diagnosis of NAFLD/NASH during follow-up (Humedica International Classification of Diseases, Ninth Revision code 571.8, and read codes for NAFLD and NASH in THIN). RESULTS: Hazard ratios (HRs) were calculated across BMI categories using BMI of 20-22.5 kg/m(2) as the reference category, adjusting for age, sex, and smoking status. Risk of recorded NAFLD/NASH increased linearly with BMI and was approximately 5 fold higher in Humedica (HR = 4.78; 95% confidence interval, 4.17-5.47) and 9 fold higher in THIN (HR = 8.93; 7.11-11.23) at a BMI of 30-32.5 kg/m(2) rising to around 10-fold higher in Humedica (HR = 9.80; 8.49-11.32) and 14-fold higher in THIN (HR = 14.32; 11.04-18.57) in the 37.5- to 40-kg/m(2) BMI category. Risk of NAFLD/NASH was approximately 50% higher in men and approximately double in those with diabetes. CONCLUSIONS: These data quantify the consistent and strong relationships between BMI and prospectively recorded diagnoses of NAFLD/NASH and emphasize the importance of weight reduction strategies for prevention and management of NAFLD. PMID- 26672641 TI - Alterations of mucosa of the larynx and hypopharynx in patients with mucopolysaccharidoses. AB - OBJECTIVE: This study aimed to: assess the mucosal alterations of the larynx and hypopharynx typical for mucopolysaccharidoses, in a standardised manner; compare the severity in different subtypes of mucopolysaccharidoses; and monitor the effect of an enzyme replacement therapy. METHODS: A classification for mucosal alterations of the larynx and hypopharynx was developed and utilised in 55 patients with mucopolysaccharidoses. Fifteen patients who started treatment with enzyme replacement therapy were followed longitudinally. RESULTS: The most severe alterations were seen in the posterior region of the larynx and the arytenoids, and in the region of the false vocal folds. The alterations were most severe in patients with mucopolysaccharidosis II. No clear trend was observed in the patients who received enzyme replacement therapy. CONCLUSION: Quantification of mucosal alterations of the hypopharynx and larynx in mucopolysaccharidoses patients can provide information about the disease's natural process and about the efficacy of enzyme replacement therapy. PMID- 26672642 TI - Effect of constant magnetic field on anaerobic digestion of algal biomass. AB - The aim of the study was to determine the impact of the constant magnetic field (CMF) application on the effectiveness of anaerobic digestion of algal biomass. The highest yield of biogas in the range of 448.9 L/kg volatile solids (VS) to 456.6 L/kg VS was observed in the variants, in which the retention time in the CMF-exposed area ranged from 144 to 216 min/d. Under these conditions, the concentration of methane in the biogas was nearly 65.0%. The increase in the contact time of the fermentation medium with the CMF-exposed area had a significant impact of reducing the effectiveness of anaerobic digestion. The lowest biodegradation was observed when the retention time was 432 min/d. Under such condition, 281.1 L of biogas/kg VS with methane content of 41.8% was obtained. A correlation between the time of exposure to CMF and the values of parameters characterizing the methane production was found. PMID- 26672643 TI - Effects of the Central Executive on Postural Control. AB - The authors focused on individual working memory (WM) capacity and examined its effect on postural control. Participants were 79 young volunteers split into two groups of low- and high WM span, based on scores from the Reading Span Test. The length of unrest was measured in the following conditions: double-leg standing as a single (D-S) task, single-leg standing as a single (S-S) task, double-leg standing as a dual (D-D) task, and single-leg standing as a dual (S-D) task. Regarding inte-group comparisons, total length was prolonged significantly between the low- and the high-span groups but only on the S-D task. The present results revealed that dual-task interference emerged in the low-span group when in a more unstable posture. PMID- 26672644 TI - Standards of the Polish Ultrasound Society - update. Sonomammography examination. PMID- 26672645 TI - Cannabinoids in the Treatment of Epilepsy. PMID- 26672646 TI - Cannabinoids in the Treatment of Epilepsy. PMID- 26672647 TI - Extensive Giant Molluscum Contagiosum in a HIV Positive Patient. AB - Molluscum contagiosum (MC) is a very common benign self-limiting cutaneous viral infection caused by molluscum contagiosum virus. Disease is self-limiting in immunocompetent individuals, while it is severe and prolonged when associated with Human Immunodeficiency Virus (HIV) infection. The widespread and refractory mollusca of HIV disease occur especially on the face. In advanced stages of immunosuppression, giant or verrucous forms of MC may occur. Molluscum contagiosum tends to take a chronic course and is usually not responsive to various treatments in immunocompromised patients. Here, we present a HIV positive male patient with extensive papulonodular lesions over face, neck, bilateral upper limbs since 2 months, diagnosed as giant molluscum contagiosum, treated with cryotherapy with little improvement for few weeks after which patient did not turn up. PMID- 26672649 TI - Corrigendum. AB - [This corrects the article DOI: 10.1177/2325967115581594.]. PMID- 26672648 TI - Age-specific non-invasive transcutaneous Doppler ultrasound derived haemodynamic reference ranges in elderly Chinese adults. AB - BACKGROUND: Whilst there is a presumption in medicine that ageing adversely affects cardiovascular function, it is unknown if resting haemodynamics are compromised in the elderly, and if so, to what degree. This study was intended to answer several questions; whether age-related changes in haemodynamics occur; whether there was a difference between the haemodynamics of ageing subjects with and without mild chronic disease; whether there was a difference in haemodynamics as measured from either the aortic or the pulmonary valve; and to establish reference ranges for this population. METHODS: Chinese adults aged over 60 years were divided into three age bands of 61-70, 71-80 and over 80 years. The haemodynamic parameters were measured using a non-invasive Doppler ultrasound based instrument, the Ultrasonic Cardiac Output Monitor (USCOM). RESULTS: One hundred and sixty-five subjects (48.5% males) were recruited. 78 (47.3%) had no known disease whilst 87 (52.7%) had mild chronic illness. A total of 21 individual haemodynamic parameters were measured or calculated for each subject. There were no significant differences in stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR) or in body surface area (BSA)-indexed parameters, SV index (SVI), cardiac index (CI) and SVR index (SVRI) across age groups, or in other indexed haemodynamic parameters. No significant differences in indexed haemodynamics were found between those subjects with and those without mild chronic disease. Small, statistically significant, but clinically insignificant, differences (< 5%) were found between the aortic and pulmonary valve measurements for SV, SVI and heart rate. CONCLUSIONS: Ageing does not have any significant effect on resting haemodynamics in the elderly population studied. Mild chronic disease does not adversely affect resting haemodynamics in this population. GENERAL SIGNIFICANCE: Reference ranges were established for 21 haemodynamic parameters, as measured by USCOM, for an elderly Chinese population but not for non-Chinese populations. PMID- 26672650 TI - Feasibility of collaborative care treatment of opioid use disorders with buprenorphine during pregnancy. AB - BACKGROUND: Medication-assisted treatment with buprenorphine or methadone is recommended for pregnant patients with opioid use disorders (OUDs) to minimize adverse maternal and neonatal outcomes. Collaborative care approaches have been successfully utilized with office-based opioid treatment with buprenorphine in primary care settings, but research is significantly limited in the obstetric setting. Our aim with this study is to demonstrate the feasibility of a collaborative care model for pregnant patients with opioid use disorder. METHODS: This is a case series of 16 pregnancies in 14 women initiated on office-based opioid treatment with buprenorphine in a perinatal mental health service embedded in 2 obstetric clinics. Patients are treated by a psychiatrist alongside their prenatal care provider and followed for up to 6 months postpartum and referred to ongoing substance abuse treatment to a community prescriber. RESULTS: The average age of the patients was 30.3 years, and an average gestational age of 23.6 weeks at the time of referral. Treatment continued until delivery in 15 (93.8%) pregnancies, with an average duration of treatment of 14.5 weeks. The majority (60%) had a cesarean delivery. Twelve (80%) infants were admitted to the Neonatal Intensive Care Unit (NICU) for monitoring or treatment of neonatal abstinence syndrome, 14 (87.5%) patients continued or resumed treatment with buprenorphine postpartum at the time of discharge from our program, and 13 (81.3%) were referred to a community prescriber. CONCLUSIONS: A collaborative care approach to buprenorphine treatment is feasible during pregnancy. Further research is needed to improve the treatment of OUD during pregnancy. PMID- 26672651 TI - [Viral zoonoses and emergence: research is just starting]. PMID- 26672652 TI - [Activation of the eIF2alpha-ATF4 pathway: an adaptative response to cellular stress]. PMID- 26672653 TI - [The Borna disease virus phosphoprotein alters the development of human GABAergic neurons]. PMID- 26672654 TI - [Custom modification in vivo of mucus properties: proof of concept and potential applications]. PMID- 26672655 TI - [Efficacy and safety of gene therapy for Wiskott-Aldrich syndrome]. PMID- 26672656 TI - [Axin-2+ hepatocytes are better at maintaining liver mass]. PMID- 26672657 TI - [Is the single nucleotide polymorphism (SNP) of CD36, a lipid-receptor, a predictor of obesity in adulthood?]. PMID- 26672659 TI - [MicroRNAs pull the strings of motile cilia]. PMID- 26672658 TI - [Locked outside: cure of chronic hepatitis C using an entry inhibitor]. PMID- 26672660 TI - [The adipose tissue macrophages: new modulators of fat mass repartition in obesity]. PMID- 26672661 TI - [Tissue-specific membrane effects of estrogen receptor alpha]. AB - Estrogen receptors (ER) are used as therapeutic targets, either for contraception or for the hormonal replacement therapy in menopausal women, but also in physiopathology for breast cancer treatment. It is therefore important to understand the tissue-specificity of the actions of ERalpha to optimize the benefits/risks ratio in each tissue. Besides the conventional nuclear ERalpha acting as a transcription factor, many studies have demonstrated that ERalpha is also able to mediate extra nuclear signaling, enabling rapid actions of estrogen. Recently, new transgenic mouse models were used to study these effects, and allowed to genetically segregate membrane versus nuclear actions of a steroid hormone receptor, demonstrating their in vivo tissue-specific roles. PMID- 26672662 TI - [Key role played by the gut associated lymphoid tissue during human immunodeficiency virus infection]. AB - The gut associated lymphoid tissue (GALT) is the site of numerous immunological disturbances during HIV-1 infection. It constitutes the largest reservoir for HIV, not or very poorly susceptible to antiretroviral therapy (ART), making it a major obstacle to HIV cure. Moreover, the GALT is involved in systemic immune activation in HIV-infected individuals: intestinal damage due to viral replication and severe CD4(+) T cell depletion in the GALT leads to microbial translocation, a key driver of immune activation, and in turn, disease progression. In this review, we describe the role of the GALT in HIV infection and we discuss therapeutic options to decrease the intestinal viral reservoir and to preserve immune function in the gut of HIV-infected people. Achieving these goals is necessary for a long-term infection control after the interruption of ART. PMID- 26672663 TI - [Is there a risk of zoonotic disease due to adenoviruses?]. AB - Every year brings another round of zoonotic viral infections. Usually they fall under the radar, but the occasional lethal epidemic brings another scare to the public and new urgency to the medical community. The types of these viruses (DNA vs. RNA genomes, enveloped vs. proteinaceous) as well as the preceding host(s) vary. Over the last 20 years, bats have been identified as an enigmatic carrier for several pathogens that have jumped the species barrier and infected humans. Factors that favour the emergence of zoonotic pathogens include the increasing overlap of the human and animal habitats, cultural activities, and the host reservoir. In this context, we asked whether bat and/or nonhuman primate adenoviruses are a risk for human health. PMID- 26672665 TI - [Neural stem cells and Notch signalling]. AB - Development and repair of the nervous system are based on the existence of neural stem cells (NSCs) able to generate neurons and glial cells. Among the mechanisms that are involved in the control of embryo or adult NSCs, the Notch signalling plays a major role. In embryo, the pathway participates in the maintenance of NSCs during all steps of development of the central nervous system which starts with the production of neurons also called neurogenesis and continues with gliogenesis giving rise to astrocytes and oligodendrocytes. During the postnatal and adult period, Notch signalling is still present in the major neurogenic areas, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus. In these regions, Notch maintains NSC quiescence, contributes to the heterogeneity of these cells and displays pleiotropic effects during the regeneration process occurring after a lesion. PMID- 26672664 TI - [Statin intolerance and associated muscular dysfunctions]. AB - Hypercholesterolemia is a major risk factor for cardiovascular diseases. The 2012 2013 survey of Canada's public health measures revealed that dyslipidemia was present in 38% of the respondents aged between 18 and 79 years. According to the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society and the Canadian Working Group Consensus, statins remain the treatment of choice for dyslipidemia and the reduction of cardiovascular risk. However, concerns and questions persist regarding statins use and safety, potential and harmful muscular side-effects, interactions with exercise, and molecular mechanisms of myotoxicity. The goal of the present review is to provide a clear picture of the clinical situation and to investigate possible mechanisms of statin-induced myopathy. A better understanding of muscle pathology in statin users is absolutely essential to minimize their muscle symptoms and to provide a sound clinical basis for the management of cardiovascular risk. PMID- 26672666 TI - [Construction of synthetic cells: from basic questions to applications]. AB - The construction of synthetic cells is a rapidly growing discipline. In this review, we discuss the last advances of the bottom-up constructive approach, in particular the construction of minimal cells. Three different paths are used to assemble cells from molecular components. The construction of protocells explores questions related to the origin of life using prebiotic molecules. The construction of minimal cells from natural molecules consists of integrating the DNA information and a simple metabolism into vesicles with the rather ambitious objective of obtaining a compartment capable of self-reproduction based on a minimal genome. The artificial cell approach consists of assembling cell-sized compartments capable of biological functions by integrating natural and synthetic molecules to construct hybrid systems with new properties. Those three avenues, all multidisciplinary and complementary, give rise to new ideas for biotechnologies and medicine. PMID- 26672667 TI - [Cancer screening: unsupported promises from Pathway Genomics]. AB - The "liquid biopsy" approach shows promise for characterization and monitoring of cancer during treatment; however a blood-based detection test for "high-risk" but asymptomatic individuals, recently introduced by Pathway Genomics, lacks supporting data and has no proven clinical utility. PMID- 26672668 TI - [A critical review of "Drug anthropology in the south: pharmaceuticalization in its margins", by Alice Desclaux and Marc Egrot]. PMID- 26672669 TI - Ultrasound quiz. PMID- 26672670 TI - Effect of X-irradiation on Citrus Canker Pathogen Xanthomonas citri subsp. citri of Satsuma Mandarin Fruits. AB - Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is one of the most important bacterial diseases of citrus. Because citrus canker is not found in many countries including European Union and Australia, Xcc is strictly regulated in order to prevent its spread. In this study, the effects of X-irradiation on Xcc growth either in the suspension or on the surface of citrus fruits were investigated. The suspension containing 1*10(7) cfu/ml of Xcc was irradiated with different absorbed doses of X-irradiation ranging from 50 to 400 Gy. The results showed that Xcc was fully dead at 400 Gy of X-irradiation. To determine the effect of X-irradiation on quarantine, the Xcc-inoculated citrus fruits were irradiated with different X-ray doses at which Xcc was completely inhibited by an irradiation dose of 250 Gy. The D10 value for Xcc on citrus fruits was found to be 97 Gy, indicating the possibility of direct application on citrus quarantine without any side sterilizer. Beside, presence of Xcc on the surface of asymptomatic citrus fruits obtained from citrus canker-infected orchards was noted. It indicated that the exporting citrus fruits need any treatment so that Xcc on the citrus fruits should be completely eliminated. Based on these results, ionizing radiation can be considered as an alternative method of eradicating Xcc for export of citrus fruits. PMID- 26672671 TI - Molecular Basis for Erythromycin Resistance in Group A Streptococcus Isolated From Skin and Soft Tissue Infections. AB - BACKGROUND: In recent years there has been an increase in the use of erythromycin in the treatment of infections caused by bacteria other than Group A Streptococcus (GAS), which has resulted in increased resistance to this antibiotic. Erythromycin and other macrolides are alternative agents for treating GAS infections in patients, who are allergic to penicillin and its derivatives. AIM: The main aim of this study was to identify frequency, pattern and genetic determinant of erythromycin resistance among the GAS isolated from skin and soft tissue infections. MATERIALS AND METHODS: A total 100 isolates of GAS were screened for erythromycin resistance by phenotypic and genotypic method. RESULTS: The results of the present study showed that 38% isolates were resistant to erythromycin. The iMLS (inducible macrolide-lincosamide-streptogramin) phenotype was predominant (55.26%) followed by M phenotype (26.32%) and cMLS (constitutive macrolide-lincosamide-streptogramin) (18.42%). CONCLUSION: Phenotypic and genotypic analysis showed that the MLSB phenotype with ermB mediated mechanism of resistance was found the most common (76.31%) followed by mefA (20.51%). The ermTR genes was absent in all the isolates. PMID- 26672672 TI - Proof of concept of the WOMED model of benign thyroid disease: Restitution of thyroid morphology after correction of physical and psychological stressors and magnesium supplementation. AB - BACKGROUND: The aim of this study was to investigate the influence of a combined supplementation with magnesium, selenium and coenzyme Q10 on the morphology of the thyroid in patients with benign diseases. The clinical examination and treatment approach aims additionally at treating musculoskeletal and psychological stress. METHODS: A group of 8 patients (5 with hyperthyroidism, 3 with hypothyroidism) who initially attended a public institution received additional treatment at our private institution. The basic pharmacological treatment, i.e. substitution or thyreostatic, was kept unchanged. The inclusion of patients required good quality ultrasound images to be available. RESULTS: Initially the changes of the musculoskeletal system were corrected. Following this, stress components were also treated. After a period of 2-4 years of supplementation we observed a normalization of thyroid morphology as evidenced on ultrasound while at the same time there was a reduction of perfusion intensity. Thyroid antibody titers decreased in the majority of cases. Failure of the treatment was seen in 2 cases of chronic thyroiditis that was present for more than 10 years. The ultrasound images of these patients suggest a possible fibrosis. CONCLUSIONS: In spite of the limitation due to the small number of cases, our observational study has delivered proof of concept for our examination and treatment model for benign thyroid disease. GENERAL SIGNIFICANCE: Our results challenge validity of the prevailing dogma of a destructive unstoppable "autoimmune" destructive process of the gland. At the same time it shows new therapeutic options for patients with thyroid disease. PMID- 26672674 TI - "I AM a Man": Manhood, Minority Men's Health and Health Equity. AB - OBJECTIVE: To consider how manhood is a key social determinant of minority men's health. DESIGN: This commentary explicates how manhood intersects with other determinants of health to shape minority men's stress responses, health behaviors and health outcomes across the life course. RESULTS: Manhood, which perpetually needs to be proven, is an aspirational identity that is defined by the intersection of age, race/ethnicity and other identities. Minority men seek to and successfully embody US-cultural and ethnic-specific aspects of manhood in their daily lives by engaging in behaviors that constantly reaffirm their gender identity through a complex internal and social calculus that varies by intra personal characteristics and context. Manhood and health are relational constructs that highlight how the salience of masculinities are shaped by perceived and actual social norms and expectations. A life course perspective adds a framework for considering how some gendered beliefs, goals and behaviors change over time while others remain static. Three life course frameworks highlight different mechanisms through which minority men's life experiences and physiological and behavioral responses to gendered social norms, beliefs and expectations become embodied as premature mortality and other health outcomes over the life course. CONCLUSION: Manhood represents an important lens to understand how minority men's identities, goals and priorities affect their health, yet the role of manhood in minority men's health is understudied and underdeveloped. To achieve health equity, it is critical to consider how manhood shapes minority men's lives and health across the life course, and to address how manhood affects gendered and non-gendered mechanisms and pathways that explain minority men's health over time. PMID- 26672673 TI - State of the Art in the Treatment of Gastrointestinal Stromal Tumors. AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. SUMMARY: From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. KEY MESSAGE: Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. PRACTICAL IMPLICATIONS: The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment. Molecular characterization of the tumor (with respect to the PDGFRA and KIT genes) is mandatory prior to imatinib therapy. Sunitinib and regorafenib are established as alternative treatments for patients demonstrating generalized disease progression on imatinib. New tyrosine kinase inhibitors such as ponatinib and crenolanib as well as drugs targeting alternative pathways are currently under investigation. Surgery and locally ablative treatments may be indicated in some metastatic patients. PMID- 26672676 TI - The 5As: A practical taxonomy for the determinants of vaccine uptake. AB - Suboptimal vaccine uptake in both childhood and adult immunisation programs limits their full potential impact on global health. A recent progress review of the Global Vaccine Action Plan stated that "countries should urgently identify barriers and bottlenecks and implement targeted approaches to increase and sustain coverage". However, vaccination coverage may be determined by a complex mix of demographic, structural, social and behavioral factors. To develop a practical taxonomy to organise the myriad possible root causes of a gap in vaccination coverage rates, we performed a narrative review of the literature and tested whether all non-socio-demographic determinants of coverage could be organised into 4 dimensions: Access, Affordability, Awareness and Acceptance. Forty-three studies were reviewed, from which we identified 23 primary determinants of vaccination uptake. We identified a fifth domain, Activation, which captured interventions such as SMS reminders which effectively nudge people towards getting vaccinated. The 5As taxonomy captured all identified determinants of vaccine uptake. This intuitive taxonomy has already facilitated mutual understanding of the primary determinants of suboptimal coverage within inter sectorial working groups, a first step towards them developing targeted and effective solutions. PMID- 26672675 TI - Relationship between CK19 expression, deregulation of normal keratinocyte differentiation pattern and high risk-human papilloma virus infection in oral and oropharyngeal squamous cell carcinoma. AB - BACKGROUND: Simple epithelial keratins appear early during embryonic development and are expressed in non-stratified, ductal and pseudo-stratified epithelial tissues. CK19, the lowest molecular weight keratin, is also expressed in basal layer of squamous epithelia of mucosal surfaces. Previous studies have shown that High Risk-Human Papilloma Virus (HR-HPV) epithelial infection induces cell immortalization via E6 and E7 viral proteins and this, in turn, impairs cytokeratin expression in cancerous cells lines derived from uterine cervix. Here, we demonstrate the possible relationship between HR-HPV(+) oral/oropharyngeal cancer and the high levels of CK19 expression. METHODS: We analyzed 38 cases of Oral Squamous Cell Carcinomas/ Oro-Pharyngeal Squamous Cell Carcinomas (OSCCs/OPSCCs) by Immunohistochemistry (IHC) using specific antibody (Ab) detecting CK19, by In Situ Hybridization (ISH) and Polymerase Chain Reaction (PCR) based methods in order to define the HPV infectious status. We also evaluated the variation of CK19 expression in UPCI-SCC-131 (HPV(-)) and UPCI-SCC 154 (HPV(+)) cell lines by immunocytochemistry (ICC) and flow cytometry. RESULTS: CK19 OSCC/OPSCC score has been identified multiplying percentage of cancer expressing cells to staining intensity. CK19 expression score in OSCCs/OPSCCs was very different between HPV(+) (mean: 288.0 +/- 24.3) and HPV(-) cancers (mean: 66.2 +/- 96.9). This difference was statistically significant (p < 0.001) with a strong evidence of correlation (p < 0.001; Spearman's R: +0.72). ROC curve analysis was performed on CK19 expression index related to HPV positivity. Heterogeneous areas of immunoreactivity varying in percentage value, intensity and/or localization were observed in normal epithelium, both perilesional and distant from the tumor with important differences between HR-HPV(+) and HR-HPV(-) carcinomas. By ICC and flow cytometry, the two analyzed cell lines were both CK19 positive but showed a different level of expression, in particular it should be noted that the UPCI-SCC-154 (HPV(+)) cell line had a higher expression than UPCI SCC-131 (HPV(-)). CONCLUSIONS: In this study we demonstrated, for the first time, strong association between CK19 up-regulation and HR-HPV(+) OSCCs/OPSCCs. This test has a good accuracy. We identified ROC curve with a cut-off > 195 for HR-HPV positive results (Sensitivity: 92.3 %; Specificity: 89.3 %). Furthermore, in OSCC/OPSCC, the CK19 test may be useful in identifying HR-HPV infection, the latter being related to HPV E7 potential to disrupt normal cytokeratin expression pattern. PMID- 26672677 TI - Current practice in Latin America of flexible ureterorenoscopy with laser for treating kidney stones. AB - INTRODUCTION: The use of flexible ureterorenoscopy for treating kidney stones has increased in recent years, with considerable worldwide variation in the surgical technique and indications. OBJECTIVES: To determine the current practice, technique variations, use and indications of flexible ureterorenoscopy for treating kidney stones in Latin American. METHODS: We sent (by email and web link) an anonymous questionnaire with 30 questions on flexible ureterorenoscopy for treating kidney stones to Latin American urologists from January 2015 to July 2015. We collected the responses through the Survey Monkey system. RESULTS: A total of 283 urologists in 15 Latin American countries participated (response rate, 10.8%); 254 answered the questionnaire completely; 52.8% were urologists from Mexico and 11% were from Argentina; 11.8% of the responders stated that they performed >100 cases per year; 15.2% considered ureterorenoscopy as the treatment of choice for stones >2cm, and 19.6% performed ureterorenoscopy in single stages for calculi measuring >2.5cm. Some 78.4% use fluoroscopy, 69.1% use a ureteral sheath in all cases, 55.8% place double-J catheters at the end of surgery, 37.3% considered a stone-free state to be 0 fragments, and 41.2% use plain radiography to assess the stone-free condition. CONCLUSIONS: Most participating urologists consider flexible ureterorenoscopy as the first-choice treatment for stones <2cm; a small percentage of these urologists perform >100 ureterorenoscopies per year. More than half of the urologists routinely used fluoroscopy and ureteral access sheath; the most common method for determining the stone-free state is plain abdominal radiography. PMID- 26672678 TI - Inclusion of children with developmental disabilities in Arab countries: A review of the research literature from 1990 to 2014. AB - BACKGROUND: In this study, a literature review was conducted to analyze studies published from 1990 to 2014 in English-written literature on inclusion of children with developmental disabilities in Arab countries. AIMS: This study sought to review and analyze research conducted on Inclusive Education (IE) in Arab countries. METHODS AND PROCEDURES: The following electronic databases were used in searching the relevant literature: ScienceDirect, SpringerLink, PsychINFO, EBSCOhost Databases, ProQuest Dissertations and Theses Database, ERIC, and Google Scholar. After the publications to be included in this study were retrieved, each study was reviewed and analyzed. Each study was examined for details such as authors, title of research, publication year, country, purpose, methods, and key findings. OUTCOMES AND RESULTS: The results showed that a total of 42 empirical studies related to inclusion of children with developmental disabilities in Arab countries have been published. More than two-thirds of these studies came from United Arab Emirates (UAE), Jordan, and Saudi Arabia. The majority of the studies were published in the last 6 years. The main parameters in these studies were: attitudes toward inclusion, barriers to inclusion, and evaluating inclusion. CONCLUSIONS AND IMPLICATIONS: The results of the current study revealed that relatively little IE research has been conducted in Arab countries. More research is warranted to test the generalizability of the results of the current study. Further research is also needed to analyze IE practices and demonstrate strategies for the effective implementation of IE in these countries. PMID- 26672679 TI - Fetal cerebral ventricular atria width of 8-10mm: A possible prenatal risk factor for adolescent treated Attention Deficit Hyperactivity Disorder (ADHD). AB - The purpose of our research was to study the in-utero and long term post-natal outcome of fetal isolated cerebral ventricular atria width between 8 and 10mm. We conducted a retrospective, observational, case-control study, of low risk pregnant women, between 1993 and 2001. One hundred and forty one fetuses with isolated cerebral ventricular atria width between 8 and 10mm, corresponding to 2 4 standard deviations above the mean, and 309 controls, with atrial width below this level, were included for the analysis. Clinical data concerning pre and post natal outcome was retrieved from computerized medical records. Matching of cases with controls was based on age, with a ratio of 2-3 controls per case. Statistical analysis included: T-test, Chi-Square, and Multiple Logistic Regression analysis. The study group was characterized by a predominance of male gender, left side involvement, and higher birth weight, compared to the control group. Long term post-natal follow-up at a mean age of 12.7 years (+/-1.9) demonstrated an adjusted odds ratio of 2.589 (95% CI 1.415-4.737, p=0.001), being diagnosed as Attention Deficit Hyperactivity Disorder (ADHD), and treated by Methylphenidate (Ritalin((r))), during childhood, compared to the control group (23.6% and 10.0% respectively) (p=0.001). Cerebral atria width was an independent factor, controlled for the only two significant variants between groups, gender and weight over 90th centile. In conclusions, our preliminary results show that fetuses with prenatal finding of isolated cerebral ventricular atria width between 8 and 10mm are more likely of being diagnosed and treated as ADHD during childhood. PMID- 26672680 TI - Sleep problems are more frequent and associated with problematic behaviors in preschoolers with autism spectrum disorder. AB - BACKGROUND: Children with autism spectrum disorder (ASD) often suffer from sleep problems that in turn correlate with behavioral problems. However, in Japan, there have been few studies of sleep problems in children with ASD. AIMS: This study compared sleep problems in preschoolers from the community and preschoolers with ASD in Japan, and examined whether sleep problems were related to problematic behaviors in ASD preschoolers. METHODS AND PROCEDURES: Sleep problems were assessed in 965 community and 193 ASD preschoolers using the Japanese Sleep Questionnaire for Preschoolers, which was developed to assess sleep problems in Japanese preschoolers. Behavioral problems were assessed in 107 ASD preschoolers using the Child Behavior Checklist. OUTCOMES AND RESULTS: Compared with community preschoolers, ASD preschoolers experienced significantly more sleep problems, including obstructive sleep apnea and parasomnias. ASD preschoolers with sleep problems exhibited more behavioral problems than those without sleep problems. The severity of sleep problems, especially insomnia, was significantly correlated with behavioral problems in ASD preschoolers. CONCLUSIONS AND IMPLICATIONS: The present study suggests that sleep problems, especially obstructive sleep apnea, are more common in ASD preschoolers than in community preschoolers. The study also shows that sleep problems, especially insomnia, are related to problematic behavior in ASD preschoolers. PMID- 26672681 TI - Sawtooth fetal heart rate pattern due to in utero fetal central nervous system injury. PMID- 26672682 TI - Macrophage activation syndrome complicating adult onset Still's disease: A single center case series and comparison with literature. AB - OBJECTIVES: Macrophage activation syndrome (MAS) is a life-threatening condition that can complicate adult onset Still's disease (AOSD). Due to its rarity, there is no clear consensus concerning treatment recommendations and outcomes. We studied the clinical manifestations and outcomes of a relatively large cohort of patients with MAS and AOSD, and compared the data with the literature reports. METHODS: We performed a retrospective review of 7 adult patients with MAS complicating AOSD at the Cleveland Clinic (CCF) over 7 years. All patients underwent bone marrow biopsies. Through MEDLINE and PubMed literature searches, we identified 48 cases of MAS/AOSD. We compared the data of the CCF and literature cohorts. RESULTS: We identified 7 patients with MAS complicating AOSD (6 females and 1 males) for our CCF cohort, with 4 cases simultaneously presenting with MAS and AOSD. The mean age at diagnosis of MAS was 41.9 +/- 20.2 years and mean follow-up time was 18.6 +/- 16.0 months. All patients had fever, arthralgias, and typical rash; 6 had leukocytosis, 4 had sore throat, and 3 had lymphadenopathy. These patients with AOSD also had MAS, with renal insufficiency and disseminated intravascular coagulation in 4, lung involvement in 3, and serositis and shock in 2. There was significant hepatic dysfunction in all patients and 6 had bi-cytopenias. At onset of MAS, all 7 patients had active AOSD. In addition to systemic glucocorticoids, 5 patients received anakinra, with 3 patients receiving combination therapy with cyclosporine. We also identified 48 cases (35 females and 13 males) for the literature cohort with the mean age at diagnosis of MAS of 40.2 +/- 16.0 years and mean follow-up time of 17.5 +/- 32.3 months. While the 2 cohorts were similar clinically, in the CCF cohort, more patients had renal insufficiency (p < 0.001), higher soluble IL-2 receptor level (p = 0.01), and lower ESR (p = 0.02) as compared with the literature cohort. All of our patients survived with a better outcome than the literature cohort. CONCLUSION: MAS can be a serious complication of active AOSD. Our study of a relatively large cohort in conjunction with literature suggests that prompt recognition and treatment with early addition of anakinra, systemic glucocorticoids, and cyclosporine as a triple regimen may improve clinical outcomes. PMID- 26672683 TI - DISTAL FIBULAR STRESS FRACTURE IN A FEMALE RECREATIONAL RUNNER: A CASE REPORT WITH MUSCULOSKELETAL ULTRASOUND IMAGING FINDINGS. AB - BACKGROUND AND PURPOSE: This case report describes a physical therapist's use of diagnostic ultrasound imaging in the decision making process used to refer a patient to a physician for a suspected fibular stress fracture. The purpose of this case report is to 1) describe the history, subjective examination, and objective examination findings of a fibular stress fracture, 2) describe the ultrasound findings associated with a fibular stress fracture, and 3) describe the decision making process of a physical therapist in the decision to refer the patient to a medical physician for further work-up. CASE DESCRIPTION: A 52-year old female recreational runner with a recent increase in running intensity self referred to a physical therapist with a 19-day history of lateral lower leg pain. Examination revealed relatively normal ankle range of motion, mild weakness of ankle invertors and evertors, no increase in pain with resisted muscle tests of the ankle, and tenderness to palpation over the fibularis brevis muscle and distal fibula. Diagnostic ultrasound examination of the fibularis muscles revealed cortical irregularity of the distal third of the fibula in the location of tenderness. OUTCOMES: The physical therapist used the abnormal ultrasound findings, running history, symptoms, and physical examination for differential diagnosis, and decided to refer the patient to a physician for further examination. Radiographs revealed a fibular stress fracture. Follow-up ultrasound imaging demonstrated a mixed hypoechoic-hyperechoic appearance of the fibular cortex typical of healing fracture and the presence of bony callus. DISCUSSION: Diagnostic ultrasound imaging is increasingly being used by physical therapists to guide rehabilitation. Ultrasound imaging of musculotendinous structures may display adjacent bone. Physical therapists should be knowledgeable of normal and abnormal bony ultrasound imaging findings. Abnormal ultrasound findings may be one sign indicating the need to refer a patient for consultation by a physician. PMID- 26672684 TI - A rapid PCR assay to characterize the intact pks15/1 gene, a virulence marker in Mycobacterium tuberculosis. AB - Intact pks15/1 is involved in the biosynthesis of phenolic glycolipids and proposed as a marker for virulence and phylogeny in tuberculosis. Identification of intact condition is achieved mainly by DNA sequencing. For this reason the aim of this study was to develop a reproducible endpoint PCR-assay to characterize it. PMID- 26672685 TI - Cancer screening after unprovoked venous thrombosis. PMID- 26672687 TI - The century behind and the century ahead. PMID- 26672686 TI - Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial. AB - BACKGROUND: Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on (18)F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism. METHODS: In an open label, multicentre, randomised study we enrolled patients from four French university hospitals. Patients aged 18 years or older, diagnosed with unprovoked venous thromboembolism (not provoked by a major inherited or acquired risk factor) were invited to participate. Patients were randomly assigned in a 1:1 ratio to a limited screening strategy (physical examination, usual laboratory tests, and basic radiographs) or a screening strategy consisting of the limited strategy plus an (18)F-FDG PET/CT scan. Randomisation was done with a dedicated central web-based randomisation system, in block sizes of six, stratified by centre, and concealed from the investigators. Patients and investigators were not masked to study group assignment. Patients were followed up for 2 years. The primary outcome was the proportion of patients with a cancer diagnosis in each group after the initial screening assessment. Analyses were conducted in modified intention-to-test and per-protocol populations. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. FINDINGS: Between March 3, 2009, and Aug 18, 2012, we enrolled and randomly assigned 399 patients; five withdrew consent, leaving 197 in each group for the modified intention-to-test analysis. After initial screening assessment, cancer was diagnosed in 11 (5.6%) patients in the (18)F-FDG PET/CT group and four (2.0%) patients in the limited screening group (absolute risk difference 3.6%, 95% CI -0.4 to 7.9; p=0.07). At the initial screening assessment, seven (64%) of the 11 cancers diagnosed in the (18)F-FDG PET/CT group were early-stage compared with two of four cancers diagnosed in the limited screening group (p=1.00). One (0.5%) occult malignancy was detected in 186 patients who had negative initial screening in the (18)F-FDG PET/CT group, compared with nine (4.7%) in 193 patients in the limited screening group (absolute risk difference 4.1%, 95% CI 0.8 to 8.4, p=0.01). Overall, five (42%) of the 12 cancers diagnosed in the (18)F-FDG PET/CT group were advanced stage, compared with seven (54%) of the 13 cancers diagnosed in the limited screening group (p=0.70). 16 patients died during follow-up, eight (4.1%) in each group. Two (1.0%) patients in the (18)F-FDG PET/CT group and five (2.5%) in the limited screening group had cancer-related deaths. INTERPRETATION: A strategy including limited screening and a (18)F-FDG PET/CT was not associated with a significantly higher rate of cancer diagnosis after unprovoked venous thromboembolism. The risk of subsequent cancer diagnosis was, however, lower in patients who had negative initial screening that included (18)F-FDG PET/CT than in patients who had negative initial limited screening. Whether or not (18)F-FDG PET/CT might be useful in a more selected population of patients with a high risk of cancer remains to be determined. FUNDING: Programme Hospitalier de Recherche Clinique (French Department of Health). PMID- 26672688 TI - The 6-elements orthodontic philosophy: Treatment goals, classification, and rules for treating. PMID- 26672691 TI - Authors' response. PMID- 26672692 TI - Intrusive force and pulp flow measurement. PMID- 26672694 TI - Can you do it all? PMID- 26672695 TI - Donald Garth Woodside: A leader for orthodontic research and education in Canada. PMID- 26672696 TI - The history of orthodontic education: A century of development and debate. AB - The history of orthodontic education in the United States spans more than 100 years. A number of exhortations have been repeated over the years by some of the best minds in orthodontics. First, our standards of excellence must be maintained. Angle set a standard for the specialty by demanding that students in his proprietary school achieve a high level of knowledge in growth and development, biomechanics, and mechanical skills; that standard is no less important today in postgraduate orthodontic departments. Second, orthodontics is not just moving teeth. Throughout our history, authors have stressed that teeth are "incidental" to orthodontics, and we need to be concerned with bone and the dentofacial complex. To be sure, much has changed about our specialty and its biologic foundations; we must adapt along with the discoveries in biology and the innovations in technology. But we should always strive for excellence--in ourselves and our specialty. PMID- 26672697 TI - History of imaging in orthodontics from Broadbent to cone-beam computed tomography. AB - The history of imaging and orthodontics is a story of technology informing biology. Advances in imaging changed our thinking as our understanding of craniofacial growth and the impact of orthodontic treatment deepened. This article traces the history of imaging in orthodontics from the invention of the cephalometer by B. Holly Broadbent in 1930 to the introduction of low-cost, low radiation-dose cone-beam computed tomography imaging in 2015. PMID- 26672698 TI - Evolving concepts of heredity and genetics in orthodontics. AB - The field of genetics emerged from the study of heredity early in the 20th century. Since that time, genetics has progressed through a series of defined eras based on a number of major conceptual and technical advances. Orthodontics also progressed through a series of conceptual stages over the past 100 years based in part on the ongoing and often circular debate about the relative importance of heredity (nature) and the local environment (nurture) in the etiology and treatment of malocclusion and dentofacial deformities. During the past 20 years, significant advancements in understanding the genomic basis of craniofacial development and the gene variants associated with dentofacial deformities have resulted in a convergence of the principles and concepts in genetics and in orthodontics that will lead to significant advancement of orthodontic treatments. Fundamental concepts from genetics and applied translational research in orthodontics provide a foundation for a new emphasis on precision orthodontics, which will establish a modern genomic basis for major improvements in the treatment of malocclusion and dentofacial deformities as well as many other areas of concern to orthodontists through the assessment of gene variants on a patient-by-patient basis. PMID- 26672699 TI - Attracting orthodontic patients via the Internet: A 20-year evolution. AB - A generation ago, attracting new patients to an orthodontic practice was often done simply by cultivating a few good referral sources. General dentists, including some who might have provided orthodontic treatment out of necessity, were generally glad to have a trusted specialist they could recommend to their patients. Although general dentists remain an important source of new patients today, many consumers now turn to the Internet for help selecting their own specialists. As orthodontists face more competition from various sources, successful clinicians will make it easy for search engines--and patients--to find their Web sites on the Internet. PMID- 26672701 TI - Can shielded brackets reduce mucosa alteration and increase comfort perception in orthodontic patients in the first 3 days of treatment? A single-blind randomized controlled trial. AB - INTRODUCTION: Orthodontic patients can experience pain and discomfort on the oral mucosa from trauma caused by friction with the brackets and the wires. In this split-mouth design, single-blind randomized controlled trial, we aimed to investigate whether brackets with a self-snapping customized plastic shield would induce less mucosa alteration and discomfort than those without the shield. METHODS: The overall sample comprised 42 patients (22 female, 20 male) from a government-funded orthodontic practice, with a mean age of 16.7 years. Eligibility criteria included, among others, no history of mouth ulcers or systemic diseases. Customized shields for the maxillary and mandibular brackets were fabricated and inserted on one side of the mouth. The null hypothesis was that bracket shielding would have no advantage. The primary outcomes were mucosal and discomfort assessments. As the secondary outcome, the numbers of spontaneous detachments of the shields were reported. Treatment allocation was mainly implemented using a random number table for selection of the intervention side. Only the raters in charge of assessing the oral mucosa were blinded to the side of the mouth where the shields had been placed. The mucosa was assessed by 3 calibrated raters at the following time points: immediately before bracket placement (baseline assessment, T0), 3 days after delivering the shields (direct assessment of intervention, T1), and 4 days after removal of the shields (indirect assessment of intervention, T2). The raters used a newly devised yardstick in which the higher the score, the more severe the alteration. Discomfort was assessed at T1 and T2 using a visual analog scale. The Mann Whitney U test was performed at the 5% level of significance. RESULTS: Of 60 patients, 42 were eligible, and 35 were randomly selected to have one side of the mouth receive the intervention. Two patients discontinued the intervention at T1, and 5 stopped at T2. Seven additional patients were recruited and completed all time points. Thus, 42 patients participated at T0, 40 at T1, and 35 at T2. Thirty five patients participated at all time points. At T1, no statistically significant difference in terms of mucosa alteration was observed between the 2 sides (median of all differences [MD], 0.0; 95% CI, 0.0-1.0; P = 0.11). The same occurred at T2 (MD, 0.0; 95% CI, 0.0-0.0; P = 1.00). The comfort level was statistically higher at T1 on the shielded side (MD, 14.0; 95% CI, 1.0-36.0; P = 0.04), whereas no difference was observed at T2 (MD, 0.0; 95% CI, 0.0-1.0, P = 0.81). No serious harm was observed. CONCLUSIONS: The customized bracket shields were effective in reducing discomfort during the first 3 days of orthodontic treatment despite no significant difference in terms of visible mucosa alteration. REGISTRATION: This trial was not registered. PROTOCOL: The protocol was not published before trial commencement. FUNDING: Expenses for the fabrication of the shields were covered by the main author (L.P.B.P.). Orthodontic materials were from the Center for Dental Specialties in Cajazeiras, Brazil. PMID- 26672700 TI - Biology of biomechanics: Finite element analysis of a statically determinate system to rotate the occlusal plane for correction of a skeletal Class III open bite malocclusion. AB - INTRODUCTION: In the absence of adequate animal or in-vitro models, the biomechanics of human malocclusion must be studied indirectly. Finite element analysis (FEA) is emerging as a clinical technology to assist in diagnosis, treatment planning, and retrospective analysis. The hypothesis tested is that instantaneous FEA can retrospectively simulate long-term mandibular arch retraction and occlusal plane rotation for the correction of a skeletal Class III malocclusion. METHODS: Seventeen published case reports were selected of patients treated with statically determinate mechanics using posterior mandible or infrazygomatic crest bone screw anchorage to retract the mandibular arch. Two dimensional measurements were made for incisor and molar movements, mandibular arch rotation, and retraction relative to the maxillary arch. A patient with cone beam computed tomography imaging was selected for a retrospective FEA. RESULTS: The mean age for the sample was 23.3 +/- 3.3 years; there were 7 men and 10 women. Mean incisor movements were 3.35 +/- 1.55 mm of retraction and 2.18 +/- 2.51 mm of extrusion. Corresponding molar movements were retractions of 4.85 +/- 1.78 mm and intrusions of 0.85 +/- 2.22 mm. Retraction of the mandibular arch relative to the maxillary arch was 4.88 +/- 1.41 mm. Mean posterior rotation of the mandibular arch was -5.76 degrees +/- 4.77 degrees (counterclockwise). The mean treatment time (n = 16) was 36.2 +/- 15.3 months. Bone screws in the posterior mandibular region were more efficient for intruding molars and decreasing the vertical dimension of the occlusion to close an open bite. The full-cusp, skeletal Class III patient selected for FEA was treated to an American Board of Orthodontics Cast-Radiograph Evaluation score of 24 points in about 36 months by en-masse retraction and posterior rotation of the mandibular arch: the bilateral load on the mandibular segment was about 200 cN. The mandibular arch was retracted by about 5 mm, posterior rotation was about 16.5 degrees , and molar intrusion was about 3 mm. There was a 4 degrees decrease in the mandibular plane angle to close the skeletal open bite. Retrospective sequential iterations (FEA animation) simulated the clinical response, as documented with longitudinal cephalometrics. The level of periodontal ligament stress was relatively uniform (<5 kPa) for all teeth in the mandibular arch segment. CONCLUSIONS: En-masse retraction of the mandibular arch is efficient for conservatively treating a skeletal Class III malocclusion. Posterior mandibular anchorage causes intrusion of the molars to close the vertical dimension of the occlusion and the mandibular plane angle. Instantaneous FEA as modeled here could be used to reasonably predict the clinical results of an applied load. PMID- 26672702 TI - Association among pain, masticatory performance, and proinflammatory cytokines in crevicular fluid during orthodontic treatment. AB - INTRODUCTION: Orthodontic patients usually complain about masticatory limitations associated with the activation of fixed appliances. The aim of this investigation was to evaluate whether orthodontic pain reflects differences in the objective evaluation of mastication and in the levels of proinflammatory cytokines in the crevicular fluid of patients undergoing orthodontic treatment. METHODS: Twenty patients with malocclusions requiring orthodontic treatment were included in this prospective study. Their pain experience, masticatory performance, and levels of interleukin 1-beta and prostaglandin E2 in crevicular fluid were evaluated at 3 times: before bracket placement, 24 hours after archwire placement, and 30 days after the initial appointment. All variables were compared with those of a control group of 25 subjects with normal occlusion. RESULTS: The masticatory performance of the patients was significantly reduced at 24 hours after bracket placement, the period in which they reported higher values of pain and had higher levels of interleukin 1-beta. The levels of prostaglandin E2 did not change in the periods evaluated, and there were no correlations between the levels of cytokines and the functional limitations observed. The only significant correlation was between pain and decreased masticatory performance. CONCLUSIONS: The masticatory performance of orthodontic patients is significantly reduced only during the period of greatest pain. However, these alterations did not correlate with any measurement of interleukin 1-beta or prostaglandin E2 in the crevicular fluid, suggesting that these solitary measurements are inadequate to predict the temporary pain and masticatory limitations experienced by patients undergoing orthodontic treatment. PMID- 26672703 TI - Antibacterial orthodontic cement to combat biofilm and white spot lesions. AB - INTRODUCTION: White spot lesions are an undesired side effect of fixed orthodontic treatment. The objective of this research was to develop an antibacterial resin-modified glass ionomer cement (RMGIC) containing nanoparticles of silver (NAg) for prevention of white spot lesions. METHODS: NAg was incorporated into a commercial RMGIC. The NAg-enhanced cement was compared with the unaltered RMGIC and with a commercially available composite that does not release fluoride. The experimental and control products were used to bond brackets to 80 extracted maxillary first premolars. Enamel shear bond strength and the adhesive remnant index scores were determined. A dental plaque microcosm biofilm model with human saliva as the inoculum was used to investigate biofilm viability. Bacteria on the sample surface and bacteria in the culture medium away from the sample surface were tested for metabolic activity, colony-forming units, and lactic acid production. RESULTS: Adding NAg to RMGIC and aging in water for 30 days did not adversely affect the shear bond strength compared with the commercial RMGIC control (P >0.1). The RMGIC with 0.1% NAg achieved the greatest reductions in colony-forming units, metabolic activity, and lactic acid production. The RMGIC with 0.1% NAg inhibited not only the bacteria on the surface, but also the bacteria away from the surface in the culture medium. Incorporation of NAg into RMGIC greatly reduced biofilm activity. CONCLUSIONS: This novel RMGIC reduced biofilm formation and plaque buildup and could inhibit white spot lesions around brackets. The method of using NAg may apply in a wide range of dental adhesives, cements, sealants, and composites to inhibit biofilm and caries. PMID- 26672704 TI - Retrospective study of 100 autotransplanted teeth with complete root formation and subsequent orthodontic treatment. AB - INTRODUCTION: Autotransplantation has become a major therapeutic option for replacing missing teeth in adult orthodontic patients. However, little systematic information is available about the long-term stability of autotransplanted teeth with complete root formation after the application of an orthodontic force. The objective of this study was to investigate the outcomes of autotransplanted teeth with complete root formation that underwent orthodontic treatment. METHODS: One hundred teeth, autotransplanted in 89 patients, were examined over a mean observation period of 5.8 years. Orthodontic force was applied with nickel titanium wires 4 to 8 weeks after autotransplantation. Root resorption, ankylosis, mobility, pocket depth, and inflammation at the recipient site were investigated clinically and with radiographs. RESULTS: The survival rate of the autotransplanted teeth was 93.0%. Abnormal findings were found in 29 teeth, including 7 lost teeth, for a success rate of 71.0%. Donor tooth type and occlusal condition of the donor tooth before transplantation were associated with abnormal findings. CONCLUSIONS: The early application of orthodontic force may increase the success rate of autotransplanted teeth, and the type and presurgical occlusal condition of donor teeth affect the success rate. PMID- 26672705 TI - Short-term effects of strain produced on a split palatal screw-type hyrax appliance after rapid maxillary expansion: A clinical trial. AB - INTRODUCTION: The aim of this study was to establish an accumulated strain pattern in different parts of rapid maxillary expansion appliances and relate them to different vertical growth patterns. A clinical study was conducted of 40 patients with posterior crossbite who required rapid palatal expansion. METHODS: Patients (mean age, 8.48 years) were recruited and treated at the Dental Hospital of Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. Strain gauges were placed on the arms of the RME hyrax screw appliance to record deformation (strain) during the expansion and the retention phases for 75 days. A finite element model was used to place the gauge at the point where the strain was most expressed. The vertical coefficient of variation was used to classify the patients by their vertical growth pattern. P = 0.05 was considered to be statistically significant. RESULTS: During the expansion phase, the highest values of accumulated strain were measured in the posterior part of the appliance for all facial biotypes, but these values passed to the anterior area at the end of the retention phase of the mesocephalic and brachycephalic patients. There was statistically significant difference in the strain of the posterior arms in accordance with the vertical growth pattern (P = 0.05) during the retention phase. At 75 days of retention, 61.25% of the arms had already begun to have strain dissipation. CONCLUSIONS: The accumulated strain pattern in the rapid maxillary expansion appliance can vary depending on the facial biotype. In the future, orthodontists should try to tailor the activation and retention protocol based on each patient's characteristics. PMID- 26672707 TI - Diagnostic performance of skeletal maturity for the assessment of midpalatal suture maturation. AB - INTRODUCTION: The aim of this study was to analyze the diagnostic performance of the cervical vertebral maturation (CVM) method in estimating accurately the stages of maturation of the midpalatal suture. METHODS: Cone-beam computed tomography (CBCT) images from 142 subjects (84 female, 58 male; mean age, 14.8 +/ 9.7 years) were analyzed by 2 calibrated examiners to define, by visual analysis, the maturational stages of the cervical vertebrae and the midpalatal suture. These CBCT images were required by orthodontists and surgeons for diagnosis and treatment purposes. Positive likelihood ratios (LHRs) were calculated to evaluate the diagnostic performance of the CVM stages in identifying the maturational stages of the midpalatal suture. RESULTS: Positive LHRs greater than 10 were found for several cervical vertebral stages (CSs), including CS1 and CS2 for the identification of midpalatal suture stages A and B, CS3 for the diagnosis of midpalatal suture stage C, and CS5 for the assessment of midpalatal suture stages D and E. These positive LHRs indicated large and often conclusive increases in the likelihood that the CVM stages were associated with specific stages of midpalatal suture maturation. At CS4, there were a moderate positive LHR for stage C and low positive LHRs for stages D and E. CONCLUSIONS: Most CVM stages can be used for the diagnosis of the stages of maturation of the midpalatal suture, so that CBCT imaging may not be necessary in these patients. In the postpubertal period, however, an assessment of the midpalatal suture maturation using CBCT images may be indicated in deciding between conventional rapid maxillary expansion and surgically assisted rapid maxillary expansion. On the other hand, if the CVM stage cannot be assessed, chronologic age may be a viable alternative to predict some midpalatal suture stages (particularly the early stages). PMID- 26672706 TI - Bone and cartilage changes in rabbit mandibular condyles after 1 injection of botulinum toxin. AB - INTRODUCTION: Temporary paralysis of the masseter muscle caused by botulinum toxin is a common treatment for temporomandibular disorders, bruxism, and muscle hypertrophy. Loss of masseter force is associated with decreased mandibular mineral density. Our objectives were (1) to establish whether bone loss at the mandibular condyle is regionally specific and (2) to ascertain whether the treatment affects the condylar cartilage. METHODS: Young adult female rabbits received a unilateral masseter injection of botulinum neurotoxin serotype A (BoNT/A, n = 31), saline solution (n = 19), or no injection (n = 3) and were also injected with bromodeoxyuridine (BrdU), a replication marker. The rabbits were killed at 4 or 12 weeks after treatment. The condyles were processed for paraffin histology. Cortical thickness, cartilage thickness, and trabecular bone areal density were measured, and replicating cells were counted after BrdU reaction. RESULTS: The BoNT/A rabbits exhibited a high frequency of defects in the condylar bone surface, occurring equally on the injected and uninjected sides. Bone loss was seen only on the side of the BoNT/A injection. Cortical as well as trabecular bone was severely affected. The midcondylar region lost the most bone. Recovery at 12 weeks was insignificant. Condylar cartilage thickness showed no treatment effect but did increase with time. The numbers of proliferating cells were similar in the treatment groups, but the BoNT/A animals showed more side asymmetry associated with the condylar defects. CONCLUSIONS: Bone loss may be a risk factor for the use of botulinum toxin in jaw muscles. PMID- 26672709 TI - Selecting subjects with high craniofacial shape homogeneity for clinical trials. AB - INTRODUCTION: Morphologic homogeneity is desirable in sample selection of clinical studies that evaluate methods of treating craniofacial discrepancies in orthodontics. The purposes of this study were to assess sample selection criteria commonly used in the orthodontic literature regarding their effectiveness in achieving morphologic homogeneity, and to propose a method that can guarantee selection of a homogeneous sample, for which the degree of homogeneity and the average skeletal pattern can be specified a priori. METHODS: Pretreatment lateral cephalograms from 170 consecutive patients (82 boys, 88 girls) aged 7 to 17 years were used. Sixteen skeletal and 4 dental landmarks were digitized and processed with Procrustes superimposition and principal component analysis. The sample was bootstrapped to a virtual population of 10,000 subjects by random sampling from the normal distribution for each principal component. A systematic literature search of randomized controlled trials showed that the most prevalent sample selection criteria, in addition to molar relationship, included overjet, ANB, and SN-GoGn. Each criterion was applied to the virtual population. The morphologic homogeneity of the samples was assessed as the percentage of shape variance of each sample relative to the shape variance of the population. RESULTS: The first 3 principal components incorporated approximately 53% of shape variability. The evaluated criteria achieved low or moderate morphologic homogeneity scores (range, 28%-63%), and the selected patients were widely spread in the shape space. Although the criteria are commonly applied for selecting samples with skeletal discrepancies, a considerable number of subjects with an average shape were selected. The proposed procedure entails selecting a skeletal pattern appropriate for the study's purpose, setting limits in shape space within which the sample should be confined, and testing candidate patients against these limits. The patients within these boundaries have, by definition, a similar shape to the selected skeletal pattern and form a homogeneous sample. CONCLUSIONS: The cephalometric variables that have been used in randomized controlled trials do not result in samples of high morphologic homogeneity. The proposed method guarantees high morphologic homogeneity. The extent of homogeneity, the average shape of the sample, and the sample's relationship to the general population's average can be specified a priori. PMID- 26672708 TI - Bone remodeling during orthodontic tooth movement in rats with type 2 diabetes. AB - INTRODUCTION: Type 2 diabetes is known to affect bone metabolism. In this study, we aimed to determine the effects of type 2 diabetes on bone remodeling during orthodontic tooth movement. METHODS: The 48 rats were divided into 4 groups: Wistar control group (n = 8), Goto-Kakizaki (GK) control group (n = 8), Wistar appliance group (n = 16), and GK appliance group (n = 16). The distances between the teeth were measured weekly. On day 42, maxillary alveolar bone specimens were obtained for histologic evaluation and determination of the gene expression levels of the receptor activator of nuclear factor ?B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG). RESULTS: No significant difference was observed in the levels of tooth movement between the 2 appliance groups. After orthodontic force application, the alveolar bone volume and osteoblast surface in the GK rats were diminished compared with those in the Wistar rats. The increase in the osteoclast surface relative to the control groups was 2.4-fold greater in the GK rats than in the Wistar rats. Significant upregulations of the RANK and OPG gene expression levels in the Wistar appliance group were observed. The RANKL/OPG ratio was increased in the GK appliance group compared with the Wistar appliance group. CONCLUSIONS: Diminished bone formation and slightly increased bone resorption were observed during orthodontic tooth movement in the rats with type 2 diabetes. PMID- 26672710 TI - Agreement between adolescents and parents or caregivers in rating adolescents' quality of life during orthodontic treatment. AB - INTRODUCTION: The purpose of this study was to assess the agreement between Brazilian adolescents and their parents or caregivers regarding the adolescents' oral health-related quality of life during orthodontic treatment. METHODS: The sample consisted of 102 adolescent-parent/caregiver pairs. Adolescents answered the short form of the child perceptions questionnaire, and the parents or caregivers answered the parental-caregiver perceptions questionnaire. These questionnaires have 14 items in common organized across 4 subscales: oral symptoms, functional limitations, emotional well-being, and social well-being. Agreement on the overall score and the subscales was determined using comparison and correlation analysis. The former was performed through comparison of the mean directional and absolute differences. The latter was analyzed using the intraclass correlation coefficient. RESULTS: The mean directional difference was significant for the oral symptoms subscale, with parents' reports lower than adolescents' reports (P = 0.012). However, it was not significant for the other 3 subscales and the overall score (P >0.05). The mean absolute difference for the overall score was 5.15, representing 9.2% of the maximum possible score. The intraclass correlation coefficient was 0.66, indicating substantial agreement. CONCLUSIONS: There was agreement between adolescents and their parents or caregivers in rating adolescents' oral health-related quality of life during orthodontic treatment. PMID- 26672711 TI - Class III malocclusion treated with distalization of the mandibular dentition with miniscrew anchorage: A 2-year follow-up. AB - This case report describes the orthodontic camouflage treatment for a 16-year-old Chinese girl with a Class III malocclusion. The treatment included extractions of the mandibular second molars, fixed appliance therapy, and miniscrew-aided mandibular arch distalization. Pretreatment, posttreatment, and 2-year follow-up records are shown. The anterior negative overjet and the Class III molar and canine relationships were corrected. The patient's facial profile was greatly improved. The mandibular third molars erupted into the second molar spaces, with acceptable intercuspation with the maxillary dentition. PMID- 26672712 TI - Integration of 3-dimensional surgical and orthodontic technologies with orthognathic "surgery-first" approach in the management of unilateral condylar hyperplasia. AB - Recent innovations in technology and techniques in both surgical and orthodontic fields can be integrated, especially when treating subjects with facial asymmetry. In this article, we present a treatment method consisting of 3 dimensional computer-aided surgical and orthodontic planning, which was implemented with the orthognathic surgery-first approach. Virtual surgical planning, fabrication of surgical splints using the computer-aided design/computer-aided manufacturing technique, and prediction of final orthodontic occlusion using virtual planning with robotically assisted customized archwires were integrated for this patient. Excellent esthetic and occlusal outcomes were obtained in a short period of 5.5 months. PMID- 26672713 TI - Effectiveness and efficiency of a CAD/CAM orthodontic bracket system. AB - INTRODUCTION: The first straight-wire appliance was introduced over 40 years ago to increase the consistency and efficiency of orthodontic treatment. More recently, computer-aided design and computer-aided manufacturing (CAD/CAM) technology has been used to create individualized orthodontic appliances. The purpose of this study was to investigate the clinical effectiveness and efficiency of CAD/CAM customized orthodontic appliances compared with direct and indirect bonded stock orthodontic brackets. METHODS: This retrospective study included 3 treatment groups: group 1 patients were direct bonded with self ligating appliances, group 2 patients were indirect bonded with self-ligating appliances, and group 3 patients were indirect bonded with CAD/CAM self-ligating appliances. Complete pretreatment and posttreatment records were obtained for all patients. The American Board of Orthodontics (ABO) Discrepancy Index was used to evaluate the pretreatment records, and the posttreatment outcomes were analyzed using the ABO Cast-Radiograph Evaluation. All data collection and analysis were completed by 1 evaluator. RESULTS: There were no statistically significant differences in the ABO Discrepancy Index or the ABO Cast-Radiograph Evaluation among the groups. Treatment times for the 3 groups were significantly different; the CAD/CAM group was the shortest at 13.8 +/- 3.4 months, compared with 21.9 +/- 5.0 and 16.9 +/- 4.1 months for the direct bonded and indirect bonded groups, respectively. The number of treatment appointments for the CAD/CAM group was significantly fewer than for the direct bonded group. CONCLUSIONS: The CAD/CAM orthodontic bracket system evaluated in this study was as effective in treatment outcome measures as were standard brackets bonded both directly and indirectly. The CAD/CAM appliance was more efficient in regard to treatment duration, although the decrease in total archwire appointments was minimal. Further investigation is needed to better quantify the clinical benefits of CAD/CAM orthodontic appliances. PMID- 26672714 TI - Litigation and Legislation. Who is entitled to what? PMID- 26672715 TI - Two-way analysis of variance: Part 1. PMID- 26672716 TI - IgG4-related disease: The utility of (18)F-FDG PET/CT in diagnosis and treatment. AB - OBJECTIVE: IgG4-related disease (IgG4-RD) is a systemic mass-forming fibro inflammatory condition which can affect nearly every organ system. Its pathophysiology remains incompletely understood, but affected tissues are characterized by a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells which cause chronic inflammation, storiform fibrosis and phlebitis. These findings on histopathological specimens are considered the gold standard for the diagnosis. Clinical signs and symptoms largely depend upon organ involvement which can be singular or multiple, synchronous or metachronous. The organs most frequently involved are the pancreas (autoimmune pancreatitis (AIP), salivary and lacrimal glands (Mickulicz disease and sclerosing sialadenitis), biliary tree (sclerosing cholangitis or cholecystitis), retroperitoneum (retroperitoneal fibrosis), aorta (periaortic fibrosis), kidneys (interstitial nephritis) and thyroid (Riedel thyroiditis). Presentation is mostly subacute and general symptoms such as weight loss, asthenia or fever are moderate, but more prevalent in multi-organ disease. Lesions often mimic malignancy, but most respond well to steroid therapy. CONCLUSION: In this contribution we present a rare entity of IgG4-RD and discuss the utility of fluorine-18-fluorodeoxyglucose ((18)F-FDG) Positron emission tomography/computed tomography (PET/CT) in the diagnosis and treatment of this condition. PMID- 26672717 TI - Can tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6) be used as prognostic markers of infection following ureteroscopic lithrotripsy and extracorporeal shock wave lithotripsy for ureteral stones? AB - OBJECTIVE: Ureteroscopic lithotripsy (URS) and Extracorporeal shock wave lithotripsy (ESWL) are highly effective for the treatment of uretral lithiasis and remain the treatment option for the majority of patients for more than two decades. In the present study we aimed to evaluate the levels of serum tumor necrosis factor A (TNFa) and interleucin 6 (IL6) in patients undergoing ESWL and URS. SUBJECTS AND METHODS: A total number of seventy patients were involved in our study. Thirty patients (17 males, 13 females), with a mean age of 43 had underwent ESWL and thirty patients (19 males, 11 females), with a mean age of 47 (range: 26-68) underwent URS lithotripsy. Ten healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-a and IL-6 were obtained before URS and ESWL and after the procedure at 1, 24, and 48 hours and at 2, 24, and 48 hours, respectively. The pre ESWL/URS and post ESWL/URS levels were compared and correlated with possible tissue damage. According to ESWL procedure we found that serumTNF-a levels were significantly increased after one hour (P<0,001) and after 24 hours (P=0.007). Furthermore, IL-6was significantly increased at 2 (P< 0,001), 24 and 48 hours post ESWL (P=0,003 and 0,002) respectively. For URS serum TNF-a levels were statistical significantly correlated preoperatively with one hour (P=0,0083) and 48 hours (P<0,001) after URS and IL-6 with 2 and 24 hours (P<0,001). In 3 patients for URS and 1 for ESWL we observed post procedure fever (>38.5C(o)). All those patients had preoperatively high values of TNF-a and Il-6 that increased at 1 and 2-hours respectively. In conclusion, high pre ESWL/URS levels of serum TNF-a and IL-6 may indicate a predisposition for post ESWL/URS inflammation and infection following URS lithotripsy or ESWL procedure. PMID- 26672718 TI - Anti-CCP antibodies are not a marker of severity in established rheumatoid arthritis: a magnetic resonance imaging study. AB - INTRODUCTION: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. OBJECTIVES: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. METHODS: Cross-sectional study with RA patients with 1-10 years of disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). RESULTS: We evaluated 56 patients, with a median (IqR) age of 55 (47.5-60.0) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42-24.97) 1.06 (0.28-1.75), 2 (0-8) and 15 (7-35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. CONCLUSION: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA. PMID- 26672719 TI - Mesoscale elastic properties of marine sponge spicules. AB - Marine sponge spicules are silicate fibers with an unusual combination of fracture toughness and optical light propagation properties due to their micro- and nano-scale hierarchical structure. We present optical measurements of the elastic properties of Tethya aurantia and Euplectella aspergillum marine sponge spicules using non-invasive Brillouin and Raman laser light scattering, thus probing the hierarchical structure on two very different scales. On the scale of single bonds, as probed by Raman scattering, the spicules resemble a combination of pure silica and mixed organic content. On the mesoscopic scale probed by Brillouin scattering, we show that while some properties (Young's moduli, shear moduli, one of the anisotropic Poisson ratios and refractive index) are nearly the same as those of artificial optical fiber, other properties (uniaxial moduli, bulk modulus and a distinctive anisotropic Poisson ratio) are significantly smaller. Thus this natural composite of largely isotropic materials yields anisotropic elastic properties on the mesoscale. We show that the spicules' optical waveguide properties lead to pronounced spontaneous Brillouin backscattering, a process related to the stimulated Brillouin backscattering process well known in artificial glass fibers. These measurements provide a clearer picture of the interplay of flexibility, strength, and material microstructure for future functional biomimicry. PMID- 26672720 TI - Introduction to the special issue from the 2014 meeting of the International Behavioral Neuroscience Society. AB - In 2013, President Obama launched what has been optimistically described as the "decade of the brain". The launch of this effort comes on the back of widespread acknowledgement that more is required to aid those suffering from mental health disorders. Specifically, a greater understanding of the neural circuitry related to behaviors specific to mental health disorders is needed. The field of research that relates the circuitry of the brain to specific aspects of behavior is referred to as behavioral neuroscience. The International Behavioral Neuroscience Society (IBNS) was founded in 1992 specifically to meet on an annual basis and present the latest research findings in this field, and to gather together the international research community to discuss issues important for the development and progress of this scientific discipline. This special issue includes reviews of topics of emerging interest and advancing knowledge in behavioral neuroscience, based on symposia presented at the 2014 IBNS meeting. Topics discussed at the annual IBNS meeting ranged from investigations of the neural mechanisms underlying bipolar disorder, schizophrenia, depression, traumatic brain injury, and risk-taking behavior, to behavioral consequences of obesity and immune dysfunction. Novel treatment areas are covered such as the use of deep brain stimulation, as well as investigation of the behavioral impacts of nicotine withdrawal and how this research will influence the development of nicotine cessation treatments. Hence, this special issue covers a wide-range of topics in behavioral neuroscience offering an insight into the challenges faced by researchers in this decade of the brain. PMID- 26672721 TI - Extra-Articular Ganglion Cysts around the Knee Joint. AB - PURPOSE: The purpose of this study was to report clinical results of open excision of extra-articular ganglion cysts around the knee joint combined with arthroscopic management of intra-articular pathologies if present. MATERIALS AND METHODS: Of the total 107 cases of cystic lesions around the knee, 23 cases of extra-articular ganglion cysts were reviewed between January 2006 and July 2011. There were 13 males and 10 females with a mean age of 48 years (range, 30 to 73 years). The mean follow-up duration was 40 months (range, 30 to 60 months). Preoperative magnetic resonance imaging (MRI) scan was done in all cases. Open surgical excision of the cyst was performed after arthroscopic management of intra-articular pathologies in all but 1 case. At the last follow-up, Lysholm and International Knee Documentation Committee (IKDC) scores were evaluated and MRI was conducted to detect recurrence. RESULTS: The mean Lysholm and IKDC scores showed significant improvement (p=0.005 and 0.013, respectively).The location of the cysts was anterior in 9, lateral in 7, medial in 6, and posterosuperior in 1. Intra-articular pathologies were found in 16/23 cases (69.6%). In 10/23 cases (43%), the cyst was connected to the knee joint. Three months postoperative MRI did not show any recurrence of ganglion cysts except for 1 case. CONCLUSIONS: In the treatment of extra-articular ganglion cysts, MRI can be useful for detecting intra-articular lesions and connecting orifices, and arthroscopic management of intra-articular pathologies with open excision of the cyst should be considered as a viable treatment option. PMID- 26672722 TI - Proportion of Brazilian diabetes patients that achieve treatment goals: implications for better quality of care. AB - BACKGROUND: Diabetes and its complications are substantial causes of morbidity and mortality, and caused approximately 5.1 million deaths worldwide in 2013. Early detection and treatment of diabetes complications can prevent their progression. OBJECT: This study compared the proportions of patients with type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) who achieved the goals of good clinical control. METHODS: Adults and elderly patients with T1DM and T2DM at a public outpatient endocrinology service in Brazil were retrospectively evaluated between 2012 and 2013. Clinical and socio demographic data were obtained from medical records and evaluated in accordance with the Brazilian Diabetes Society Guidelines. Care process measures, outcomes indicators, and supporting process measures were evaluated. RESULTS: A total of 1031 records were analyzed: 29 and 71 % of patients had T1DM and T2DM, respectively. T2DM patients had significantly higher BMI than T1DM patients (overweight and obesity in 85.1 vs. 47.5 %, p < 0.01). The follow-up periods for diabetes and number of clinical visits to the endocrinology service were significantly greater among T1DM patients than T2DM patients (p < 0.01). However, T2DM patients required significantly more other (i.e., non-endocrinological) healthcare services (p < 0.01). HbA1c was significantly lower in T2DM patients (p < 0.01). Moreover, blood pressure and triglycerides were significantly higher in T2DM patients (p < 0.01), whereas total cholesterol and low-density lipoprotein were significantly lower in T2DM patients (p < 0.01). Only 0.5 % of the patients achieved all targets, and 1.1 % did not achieve any. CONCLUSIONS: The achievement of goals of good clinical practice varies among the parameters evaluated. Almost no patients achieved all targets. Many patients are overweight and do not achieve targets for HbA1c, lipid profile, or blood pressure control. PMID- 26672723 TI - Comparative Effectiveness of Esophagectomy Versus Endoscopic Treatment for Esophageal High-grade Dysplasia. AB - OBJECTIVE: The purpose of this study is to determine the comparative effectiveness of esophagectomy versus endoscopic mucosal resection followed by radiofrequency ablation (EMR-RFA) for the treatment of Barrett esophagus with high-grade dysplasia (HGD). BACKGROUND: HGD of the esophagus may be managed by surgical resection or EMR-RFA. National guidelines suggest that EMR-RFA is effective at eradicating HGD. The comparative effectiveness and cost effectiveness of EMR-RFA versus esophagectomy for HGD remains unclear. METHODS: A decision-analysis model was constructed to represent 3 management strategies for HGD: (1) esophagectomy, (2) EMR-RFA, and (3) endoscopic surveillance. Estimates for model variables were obtained from literature review, and costs were estimated from Medicare fee schedules. Costs and utilities were discounted at an annual rate of 3%. The baseline model was adjusted for alternative age groups and high-risk dysplastic variants. One-way and multivariable probabilistic sensitivity analyses were conducted. RESULTS: For a 65-year-old patient, compared to esophagectomy, EMR-RFA yields equivalent utility (11.5 vs 11.4 discounted quality-adjusted life years) with lower total cost ($52.5K vs $74.3K) over the first 20 years. Dominance of EMR-RFA over esophagectomy persists for all age groups. Patients with diffuse or ulcerated HGD are more effectively treated with esophagectomy. Model outcomes are sensitive to estimated rates of disease progression and postintervention utility parameters. CONCLUSIONS: Existing evidence supports EMR-RFA over esophagectomy for the treatment of esophageal HGD. Long-term outcomes and more definitive quality-of-life studies for both interventions are crucial to better inform decision-making. PMID- 26672724 TI - AHNAK is downregulated in melanoma, predicts poor outcome, and may be required for the expression of functional cadherin-1. AB - The aim of this study was to further our understanding of the transformation process by identifying differentially expressed proteins in melanocytes compared with melanoma cell lines. Tandem mass spectrometry incorporating iTRAQ reagents was used as a screen to identify and comparatively quantify the expression of proteins in membrane-enriched samples isolated from primary human melanocytes or three melanoma cells lines. Real-time PCR was used to validate significant hits. Immunohistochemistry was used to validate the expression of proteins of interest in melanocytes in human skin and in melanoma-infiltrated lymph nodes. Publically available databases were examined to assess mRNA expression and correlation to patient outcome in a larger cohort of samples. Finally, preliminary functional studies were carried out using siRNAs to reduce the expression of a protein of interest in primary melanocytes and in a keratinocyte cell line. Two proteins, AHNAK and ANXA2, were significantly downregulated in the melanoma cell lines compared with melanocytes. Downregulation was confirmed in tumor cells in a subset of human melanoma-infiltrated human lymph nodes compared with melanocytes in human skin. Examination of Gene Expression Omnibus database data sets suggests that downregulation of AHNAK mRNA and mutation of the AHNAK gene are common in metastatic melanoma and correlates to a poor outcome. Knockdown of AHNAK in primary melanocytes and in a keratinocyte cell line led to a reduction in detectable cadherin-1. This is the first report that we are aware of which correlates a loss of AHNAK with melanoma and poor patient outcome. We hypothesize that AHNAK is required for the expression of functional cadherin-1. PMID- 26672725 TI - Adaption By Low Dose Radiation Exposure: A Look at Scope and Limitations for Radioprotection. AB - The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to "as low as reasonably achievable" (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations. PMID- 26672727 TI - Intrapartum sonography - eccentricity or necessity? PMID- 26672726 TI - Consensus on the Prevention, Screening, Early Diagnosis and Treatment of Colorectal Tumors in China: Chinese Society of Gastroenterology, October 14-15, 2011, Shanghai, China. AB - BACKGROUND: Colorectal cancer (CRC) is steadily increasing in China. Colorectal adenoma (CRA) is the most important precancerous disease of CRC. Screening for colorectal tumors can aid early diagnosis. Advances in endoscopic mucosal resection and endoscopic submucosal dissection can aid the early treatment of colorectal tumors. Furthermore, because of high risk of recurrence after removal of adenomas under endoscopy, factors contributing to recurrence, the follow-up mode and the interval established, and the feasibility of application and the time of various chemical preventions should be concerned. However, a relevant consensus on the screening, early diagnosis and treatment, and prevention of colorectal tumors in China is lacking. SUMMARY: The consensus recommendations include epidemiology, pathology, screening, early diagnosis, endoscopic treatment, monitoring and follow-up, and chemoprevention of colorectal tumors in China. KEY MESSAGE: This is the first consensus on the prevention, screening, early diagnosis and treatment of CRA and CRC in China based on evidence in the literature and on local data. PRACTICAL IMPLICATIONS: Through reviewing the literature, regional data and passing the consensus by an anonymous vote, gastroenterology experts from all over China launch the consensus recommendations in Shanghai. The incidence and mortality of CRC in China has increased, and the incidence or detection rate of CRA has increased rapidly. Screening for colorectal tumors should be performed at age 50-74 years. Preliminary screening should be undertaken to find persons at high risk, followed by colonoscopy. A screening cycle of 3 years is recommended for persistent interventions. Opportunistic screening is a mode suitable for the current healthcare system and national situation. Colonoscopy combined with pathological examination is the standard method for the diagnosis of colorectal tumors. CRA removal under endoscopy can prevent CRC to some extent, but CRA has an obvious recurrence trend. The follow-up interval after the removal or surgery of colorectal tumors should be different with lesions. Primary prevention of CRA includes improved diet with more fiber, supplements containing calcium and vitamin D, supplements containing folic acid for those with low hemoglobin levels, and cessation of tobacco smoking. Non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors have been recognized to prevent recurrence after adenoma removal. PMID- 26672729 TI - Spontaneous Rupture of Adenocarcinoma of Meckel's Diverticulum- A Rare Entity. AB - Meckel's diverticulum is a true diverticulum from remnant of vitelline duct. It is most common congenital anomaly of intestine. It is associated with intestinal atresia and anorectal anomalies. It contains heterotrophic epithelium. Most common heterotrophic mucosa is gastric followed by pancreatic tissue. Adenocarcinoma arising from Meckel's diverticulum is very rare. Spontaneous perforation of adenocarcinoma rarely reported. Most of perforation reported in Meckel's diverticulum diagnosed during intraoperative period. This is a case report of spontaneous rupture of adenocarcinoma of Meckel's diverticulum, which was managed with primary resection and ileostomy. PMID- 26672731 TI - Quantifying highly efficient incoherent energy transfer in perylene-based multichromophore arrays. AB - Multichromophore perylene arrays were designed and synthesized to have extremely efficient resonance energy transfer. Using broadband ultrafast photoluminescence and transient absorption spectroscopies, transfer timescales of approximately 1 picosecond were resolved, corresponding to efficiencies of up to 99.98%. The broadband measurements also revealed spectra corresponding to incoherent transfer between localized states. Polarization resolved spectroscopy was used to measure the dipolar angles between donor and acceptor chromophores, thereby enabling geometric factors to be fixed when assessing the validity of Forster theory in this regime. Forster theory was found to predict the correct magnitude of transfer rates, with measured ~2-fold deviations consistent with the breakdown of the point-dipole approximation at close approach. The materials presented, along with the novel methods for quantifying ultrahigh energy transfer efficiencies, will be valuable for applications demanding extremely efficient energy transfer, including fluorescent solar concentrators, optical gain, and photonic logic devices. PMID- 26672728 TI - Residential Segregation and Diabetes Risk among Latinos. AB - OBJECTIVE: To examine whether residence in ethnically segregated metropolitan areas is associated with increased diabetes risk for Latinos in the United States. METHODS: Population data from the 2005 Behavioral Risk Factor Surveillance System and the 2005 American Community Survey were used to determine whether higher levels of Latino-White segregation across metropolitan statistical areas (MSAs) in the United States is associated with increased diabetes risk among Latinos (n=7462). RESULTS: No significant relationship (P<.05) between levels of segregation and diabetes risk was observed. CONCLUSION: The research literature examining the impact of residential segregation on health outcomes remains equivocal for Latinos. PMID- 26672732 TI - Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder. AB - One of the basic abdominal organs that is assessed during transabdominal ultrasound examination for urological reasons is the urinary bladder. The bladder must be filled with urine. This is a prerequisite for a reliable assessment and, at the same time, an acoustic window in examining adjacent structures and organs, for instance the prostate gland. In some cases, doubts occur with respect to the nature of lesions detected. The paper presents anatomic lesions, defects and pathologies which might be erroneously interpreted as tumors of the urinary bladder, i.e. transitional cell carcinoma of the urinary bladder. The following lesions are discussed: 1) anatomic defects (including urachus remnants, ligaments that stabilize the bladder or cyst in the opening of the ureter into the bladder ureterocele); 2) tumor- like lesions in the lumen of the urinary bladder (such as blood clots, fungus balls, stones or foreign bodies); 3) bladder wall pathologies (i.e. cystitis or endometriosis), focal decidual transformation of stromal cells or inflammatory pseudotumor; 4) lesions impressing on the bladder from the outside (the mesentery of the sigmoid colon, the bowel, pathological lesions in organs adjacent to the urinary bladder, inflammatory infiltration, vasogenic compression of the bladder, pelvic lipomatosis, pathological lesions of the pubic symphysis); 5) postoperative lesions. All these lesions may mimic carcinoma of the urinary bladder in sonography. Bearing this fact in mind is significant in establishing a diagnosis. Due to the malignant character of carcinoma of the urinary bladder and the need for aggressive surgical treatment, a correct diagnosis of this disease is essential for patients, particularly because the lack of adequate treatment and delayed treatment considerably affect prognosis. PMID- 26672733 TI - Fetal and postnatal ovine mesenteric vascular reactivity. AB - BACKGROUND: Intestinal circulation and mesenteric arterial (MA) reactivity may play a role in preparing the fetus for enteral nutrition. We hypothesized that MA vasoreactivity changes with gestation and vasodilator pathways predominate in the postnatal period. METHODS: Small distal MA rings (0.5-mm diameter) were isolated from fetal (116-d, 128-d, 134-d, and 141-d gestation, term ~ 147 d) and postnatal lambs. Vasoreactivity was evaluated using vasoconstrictors (norepinephrine (NE) after pretreatment with propranolol and endothelin-1(ET-1)) and vasodilators (NO donors A23187 and s-nitrosopenicillamine (SNAP)). Protein and mRNA assays for receptors and enzymes (endothelin receptor A, alpha-adrenergic receptor 1A (ADRA1A), endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase5 (PDE5)) were performed in mesenteric arteries. RESULTS: MA constriction to NE and ET-1 peaked at 134 d. Relaxation to A23187 and SNAP was maximal after birth. Basal eNOS activity was low at 134 d. ADRA1A mRNA and protein increased significantly at 134 d and decreased postnatally. sGC and PDE5 protein increased from 134 to 141 d. CONCLUSION: Mesenteric vasoconstriction predominates in late-preterm gestation (134 d; the postconceptional age with the highest incidence of necrotizing enterocolitis (NEC)) followed by a conversion to vasodilatory influences near the time of full-term birth. Perturbations in this ontogenic mechanism, including preterm birth, may be a risk factor for NEC. PMID- 26672735 TI - Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy. AB - BACKGROUND: In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. METHODS: We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. RESULTS: We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. CONCLUSION: These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID- 26672734 TI - Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration. AB - BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends upper and lower limits of preductal saturations (SpO2) extrapolated from studies in infants resuscitated in room air. These limits have not been validated in asphyxia and lung disease. METHODS: Seven control term lambs delivered by cesarean section were ventilated with 21% O2. Thirty lambs with asphyxia with meconium aspiration were randomly assigned to resuscitation with 21% O2 (n = 6), 100% O2 (n = 6), or initiation with 21% O2 followed by variable FIO2 to maintain NRP target SpO2 ranges (n = 18). Hemodynamic and ventilation parameters were recorded for 15 min. RESULTS: Control lambs maintained preductal SpO2 near the lower limit of NRP target range. Asphyxiated lambs had low SpO2 (38 +/- 2%), low arterial pH (6.99 +/- 0.01), and high PaCO2 (96 +/- 7 mm Hg) at birth. Resuscitation with 21% O2 resulted in SpO2 values below the target range with low pulmonary blood flow (Qp) compared to variable FIO2 group. The increase in PaO2 and Qp with variable FIO2 resuscitation was similar to control lambs. CONCLUSION: Maintaining SpO2 as recommended by NRP by actively adjusting inspired O2 leads to effective oxygenation and higher Qp in asphyxiated lambs with lung disease. Our findings support the current NRP SpO2 guidelines for O2 supplementation during resuscitation of an asphyxiated neonate. PMID- 26672736 TI - Serum hepcidin in infants born after 32 to 37 wk of gestational age. AB - BACKGROUND: Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additional indicator of ID in preterm infants, next to ferritin. METHODS: In a prospective observational study, we analyzed serum hepcidin in 111 infants born after 32+0 to 36+6 wk gestational age during the first 4 mo of life. RESULTS: Hepcidin concentrations decreased during the first 4 mo of life, and concentrations were lower in infants with ID compared to those without ID. Infants who developed ID at the age of 4 mo had already significantly lower levels of hepcidin at 1.5 mo of age, while ferritin was already significantly lower at the age of 1 wk. CONCLUSION: Hepcidin concentrations of late preterm infants decrease during the first 4 mo of life. This decrease, which parallels a decrease of ferritin concentration, we interpret as a physiological response, aiming to increase iron availability. Hepcidin concentrations are lower in infants with ID compared with those without ID, with a notable change already observed at 1.5 mo of age. Hepcidin can be used as an early marker of ID, although an additive value of hepcidin over ferritin in the diagnosis of ID is not present. PMID- 26672737 TI - Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia. AB - BACKGROUND: Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP dependent retinol transport in a nitrofen model of CDH. METHODS: Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. RESULTS: Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. CONCLUSION: Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels. PMID- 26672738 TI - Cell cycle related genes up-regulated in human colorectal development predict the overall survival of late-stage colorectal cancer patients. AB - A tumor can be perceived as a special "organ" that undergoes aberrant and poorly regulated organogenesis. Embryonic development and carcinogenesis share striking similarities in their cellular behavior and underlying molecular mechanisms. This intimate association makes embryonic development a viable reference model for studying cancer thereby circumventing the potentially misleading complexity of tumor heterogeneity. Therefore, on the basis of global expression profile, the genes simultaneously activated (up-regulated in terms of expression profile) or suppressed (down-regulated) in both the embryonic development and cancer stage, probably contain profound information on the molecular mechanism of cancer. In this study, the Affymetrix expression profile of 1593 colorectal cancer samples was downloaded from Gene Expression Omnibus. The 1396 differentially expressed probes were robustly obtained using 660 colorectal normal and cancer samples, the expression pattern of which was analyzed using our human colorectal developmental data. All of these 1396 probes were classified into 27 distinct patterns based on their expression patterns during the developmental process. By means of gene set enrichment analysis, we collected 393 V probes simultaneously up-regulated in both development and carcinogenesis and 207 A probes down-regulated in both. Functional enrichment analysis indicated that the V probes were significantly related to cell cycle regulation. Notably, 28 cell-cycle related probes within the V probe group were found to be significantly associated with an overall survival of Stage III/IV patients (GSE17536 cross validation, n = 96, p = 5.70 * 10(-3); GSE29621, n = 36, p = 1.70 * 10(-3); GSE39084, n = 38, p = 0.05; GSE39582, n = 264, p = 0.047; GSE17537, n = 36, p = 5.90 * 10(-3)). PMID- 26672739 TI - Models to teach lung sonopathology and ultrasound-guided thoracentesis. AB - Lung sonography allows rapid diagnosis of lung emergencies such as pulmonary edema, hemothorax or pneumothorax. The ability to timely diagnose an intraoperative pneumothorax is an important skill for the anesthesiologist. However, lung ultrasound exams require an interpretation of not only real images but also complex acoustic artifacts such as A-lines and B-lines. Therefore, appropriate training to gain proficiency is important. Simulated environment using ultrasound phantom models allows controlled, supervised learning. We have developed hybrid models that combine dry or wet polyurethane foams, porcine rib cages and human hand simulating a rib cage. These models simulate fairly accurately pulmonary sonopathology and allow supervised teaching of lung sonography with the immediate feedback. In-vitro models can also facilitate learning of procedural skills, improving transducer and needle positioning and movement, rapid recognition of thoracic anatomy and hand - eye coordination skills. We described a new model to teach an ultrasound guided thoracentesis. This model consists of the experimenter's hand placed on top of the water-filled container with a wet foam. Metacarpal bones of the human hand simulate a rib cage and a wet foam simulates a diseased lung immersed in the pleural fluid. Positive fluid flow offers users feedback when a simulated pleural effusion is accurately assessed. PMID- 26672740 TI - Nucleotides containing variously modified sugars: energetics, structure, and mechanical properties. AB - The influence of various sugar residue modifications on intrinsic energetic, conformational, and mechanical properties of 2'-deoxyribonucleotide-5' monophosphates (dNs) was comprehensively investigated using modern quantum chemical approaches. In total, fourteen sugar modifications, including double bonds and heteroatoms (S and N) inside the sugar ring, as well as fluorination in various positions, were analyzed. Among hundreds of possible conformational states of dNs, only two - AI and BI, corresponding to the most biologically significant forms of a double-helical DNA, were considered for each dN. It was established that the most of the studied modifications tend to strongly stabilize either AI or BI conformation of dNs both in the gas phase and in aqueous solution (modelled by implicit solvent models). Therefore, some of these modifications can be used as a tool for reducing structural polymorphism of nucleic acids in solution as well as for designing oligonucleotides with specific structural features. The evaluation of relaxed force constants (RFC) for glycosidic bonds suggests that the majority of the studied modifications of the sugar residue yield increased strengths of glycosidic bonds in dNs, and can therefore be used for designing modified nucleic acids with an increased resistance to abasic lesions. The most significant reinforcement of the glycosidic bond occurs in dNs containing the CF2 group instead of the O4' oxygen and the fluorine atom at the 2'-alpha-position. The calculation of the RFC and vibrational root-mean-square (VRMS) deviations for conformational degrees of freedom revealed a strong dependence between mechanical properties of dNs and their energetic characteristics. In particular, electronic energies of AI and BI conformers of dNs calculated in vacuo are closely connected with the values of relaxed force constants (RFC) for the delta angle: the higher RFC(delta) values correspond to more energetically favorable conformers. PMID- 26672741 TI - Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients. AB - BACKGROUND: Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes. METHODS: We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores. RESULTS: GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both). CONCLUSION: GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss. PMID- 26672743 TI - Recommendations regarding imaging of the central nervous system in fetuses and neonates. AB - An abnormal presentation of the central nervous system in a fetus during a screening examination is an indication for extended diagnosis, the aim of which is to explain the character of such an anomaly (a congenital defect, destructive effect of intrauterine infection or abnormality with reasons that are difficult to explain). Knowledge of normal development sequence of the fetal brain, which is discussed in this paper, is the basis for correct interpretation of imaging findings. Together with the increase in survival of preterm neonates, a high risk of early brain damage is still a problem in this extremely immature population. Therefore, imaging examinations become necessary. The paper presents intrauterine and postnatal risk factors of early brain damage as well as classification of such lesions, of hemorrhagic and hypoxic-ischemic etiology. The diagnosis of the cerebellum damage, which is currently believed to be a significant cause of autism, is emphasized. The evolution of lesions over time is also presented. Moreover, the elements of diagnosis important for prognosis are stressed. The standards of imaging examinations of the central nervous system include the schedule of ultrasound examinations and provide indications for extended diagnosis with the use of magnetic resonance imaging. PMID- 26672742 TI - Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis. AB - Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research. PMID- 26672744 TI - Silver(I), gold(I) and palladium(II) complexes of a NHC-pincer ligand with an aminotriazine core: a comparison with pyridyl analogues. AB - Dinuclear silver, di- and tetra-nuclear gold, and mononuclear palladium complexes with chelating C,N,C diethylaminotriazinyl-bridged bis(NHC) pincer ligands were prepared and characterised. The silver and gold complexes exist in a twisted, helical conformation in both the solution- and the solid state. In contrast, an analogous dinuclear gold complex with pyridyl-bridged NHCs exists in a linear conformation. Computational studies have been performed to rationalise the formation of twisted/helical vs. linear forms. PMID- 26672746 TI - Erratum to: A disorder of surfactant metabolism without identified genetic mutations. PMID- 26672745 TI - BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model. AB - BACKGROUND: 2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) is a derivative from 6 arylindeno[1,2-c]quinoline. Our previous study showed the anti-cancer potential of BPIQ compared to its two analogues topotecan and irinotecan. In the study, the aim is to investigate the potency and the mechanism of BPIQ against lung cancer cells. METHODS: Both in vitro and zebrafish xenograft model were performed to examine the anti-lung cancer effect of BPIQ. Flow cytometer-based assays were performed for detecting apoptosis and cell cycle distribution. Western blot assay was used for detecting the changes of apoptotic and cell cycle-associated proteins. siRNA knockdown assay was performed for confirming the apoptotic role of Bim. RESULTS: Both in vitro and zebrafish xenograft model demonstrated the anti-lung cancer effect of BPIQ. BPIQ-induced proliferative inhibition of H1299 cells was achieved through the induction of G2/M-phase arrest and apoptosis. The results of Western blot showed that BPIQ-induced G2/M-phase arrest was associated with a marked decrease in the protein levels of cyclin B and cyclin-dependent kinase 1 (CDK1). The up-regulation of pro-apoptotic Bad, Bim and down-regulation of pro-survival XIAP and survivin was observed following BPIQ treatment. CONCLUSIONS: BPIQ-induced anti-lung cancer is involved in mitochondrial apoptosis. BPIQ could be a promising anti-lung cancer drug for further applications. PMID- 26672747 TI - Genetics, Morphology, Advertisement Calls, and Historical Records Distinguish Six New Polyploid Species of African Clawed Frog (Xenopus, Pipidae) from West and Central Africa. AB - African clawed frogs, genus Xenopus, are extraordinary among vertebrates in the diversity of their polyploid species and the high number of independent polyploidization events that occurred during their diversification. Here we update current understanding of the evolutionary history of this group and describe six new species from west and central sub-Saharan Africa, including four tetraploids and two dodecaploids. We provide information on molecular variation, morphology, karyotypes, vocalizations, and estimated geographic ranges, which support the distinctiveness of these new species. We resurrect Xenopus calcaratus from synonymy of Xenopus tropicalis and refer populations from Bioko Island and coastal Cameroon (near Mt. Cameroon) to this species. To facilitate comparisons to the new species, we also provide comments on the type specimens, morphology, and distributions of X. epitropicalis, X. tropicalis, and X. fraseri. This includes significantly restricted application of the names X. fraseri and X. epitropicalis, the first of which we argue is known definitively only from type specimens and possibly one other specimen. Inferring the evolutionary histories of these new species allows refinement of species groups within Xenopus and leads to our recognition of two subgenera (Xenopus and Silurana) and three species groups within the subgenus Xenopus (amieti, laevis, and muelleri species groups). PMID- 26672748 TI - Genome-Wide Gene by Environment Interaction Analysis Identifies Common SNPs at 17q21.2 that Are Associated with Increased Body Mass Index Only among Asthmatics. AB - Asthmatics have an increased risk of being overweight/obese. Although the underlying mechanisms of this are unclear, genetic factors are believed to play an essential role. To identify common genetic variants that are associated with asthma-related BMI increase, we performed a genome-wide gene by environment (asthma) interaction analysis for the outcome of BMI in the Multi-Ethnic Study of Atherosclerosis (MESA) study (N = 2474 Caucasians, 257 asthmatics), and replicated findings in the Framingham Heart Study (FHS) offspring cohort (N = 1408 Caucasians, 382 asthmatics). The replicable tagging SNP, rs2107212, was further examined in stratified analyses. Seven SNPs clustered in 17q21.2 were identified to be associated with higher BMI among asthmatics (interaction p < 5*10-7 in MESA and p < 0.05 in FHS). In both MESA and FHS asthmatics, subjects carrying the A allele on rs2107212 had significantly higher odds of obesity than non-carriers, which was not the case for non-asthmatics. We further examined BMI change subsequent to asthma diagnosis over a period of 26 years in FHS and demonstrated greater BMI increase among asthmatics compared to non-asthmatics. Asthmatics carrying the A allele at rs2107212 had significantly greater net BMI increase over the 26-year period compared to non-asthmatics. In this study, we found that common genetic variants on 17q21.2 are associated with post-asthma BMI increase among Caucasians. This finding will help elucidate pathways involved in the comorbidity of asthma and obesity. PMID- 26672750 TI - Correction: Cognition of and Demand for Education and Teaching in Medical Statistics in China: A Systematic Review and Meta-Analysis. PMID- 26672749 TI - MHC Class I Chain-Related Gene A Polymorphisms and Linkage Disequilibrium with HLA-B and HLA-C Alleles in Ocular Toxoplasmosis. AB - This study investigated whether polymorphisms of the MICA (major histocompatibility complex class I chain-related gene A) gene are associated with eye lesions due to Toxoplasma gondii infection in a group of immunocompetent patients from southeastern Brazil. The study enrolled 297 patients with serological diagnosis of toxoplasmosis. Participants were classified into two distinct groups after conducting fundoscopic exams according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of the ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping of the MICA and HLA alleles was performed by the polymerase chain reaction-sequence specific oligonucleotide technique (PCR-SSO; One Lambda(r)) and the MICA-129 polymorphism (rs1051792) was identified by nested polymerase chain reaction (PCR-RFLP). Significant associations involving MICA polymorphisms were not found. Although the MICA*002~HLA-B*35 haplotype was associated with increased risk of developing ocular toxoplasmosis (P-value = 0.04; OR = 2.20; 95% CI = 1.05-4.60), and the MICA*008~HLA-C*07 haplotype was associated with protection against the development of manifestations of ocular toxoplasmosis (P-value = 0.009; OR: 0.44; 95% CI: 0.22-0.76), these associations were not statistically significant after adjusting for multiple comparisons. MICA polymorphisms do not appear to influence the development of ocular lesions in patients diagnosed with toxoplasmosis in this study population. PMID- 26672751 TI - The Burden of Tick-Borne Encephalitis in Disability-Adjusted Life Years (DALYs) for Slovenia. AB - BACKGROUND: Tick-borne encephalitis (TBE) presents an increasing burden in many parts of Europe, Asian Russia, Siberia, Asian former USSR and Far East. Incidence can be considered as one way to express the burden. A more comprehensive measure concerns disability-adjusted life years (DALYs), better characterizing the full burden of TBE. TBE burden in DALYs has not yet been estimated, nor has it been specified by the Global Burden of Disease (GBD) studies. OBJECTIVE: The purpose of the present study is to estimate the burden of TBE in Slovenia, expressed in DALYs, both from the population and individual perspectives. We discuss the impact of TBE burden on public health and potential strategies to reduce this burden in Slovenia. METHODS: The burden of TBE is estimated by using the updated DALYs' methodology first introduced in the GBD project. The DALYs? calculations are based on the health outcomes of the natural course of the disease being modelled. Corrections for under-reporting and under-ascertainment are applied. The impact of uncertainty in parameters in the model was assessed using sensitivity analyses. RESULTS: From the population perspective, total DALYs amount to 3,450 (167.8 per 100,000 population), while from the individual perspective they amount to 3.1 per case in 2011. Notably, the consequences of TBE present a larger burden than TBE itself. CONCLUSIONS: TBE presents a relatively high burden expressed in DALYs compared with estimates for other infectious diseases from the GBD 2010 study for Slovenia. Raising awareness and increasing vaccination coverage are needed to reduce TBE and its consequences. PMID- 26672752 TI - Intermediate Megavoltage Photon Beams for Improved Lung Cancer Treatments. AB - The goal of this study is to evaluate the effects of intermediate megavoltage (3 MV) photon beams on SBRT lung cancer treatments. To start with, a 3-MV virtual beam was commissioned on a commercial treatment planning system based on Monte Carlo simulations. Three optimized plans (6-MV, 3-MV and dual energy of 3- and 6 MV) were generated for 31 lung cancer patients with identical beam configuration and optimization constraints for each patient. Dosimetric metrics were evaluated and compared among the three plans. Overall, planned dose conformity was comparable among three plans for all 31 patients. For 21 thin patients with average short effective path length (< 10 cm), the 3-MV plans showed better target coverage and homogeneity with dose spillage index R50% = 4.68+/-0.83 and homogeneity index = 1.26+/-0.06, as compared to 4.95+/-1.01 and 1.31+/-0.08 in the 6-MV plans (p < 0.001). Correspondingly, the average/maximum reductions of lung volumes receiving 20 Gy (V20Gy), 5 Gy (V5Gy), and mean lung dose (MLD) were 7%/20%, 9%/30% and 5%/10%, respectively in the 3-MV plans (p < 0.05). The doses to 5% volumes of the cord, esophagus, trachea and heart were reduced by 9.0%, 10.6%, 11.4% and 7.4%, respectively (p < 0.05). For 10 thick patients, dual energy plans can bring dosimetric benefits with comparable target coverage, integral dose and reduced dose to the critical structures, as compared to the 6 MV plans. In conclusion, our study indicated that 3-MV photon beams have potential dosimetric benefits in treating lung tumors in terms of improved tumor coverage and reduced doses to the adjacent critical structures, in comparison to 6-MV photon beams. Intermediate megavoltage photon beams (< 6-MV) may be considered and added into current treatment approaches to reduce the adjacent normal tissue doses while maintaining sufficient tumor dose coverage in lung cancer radiotherapy. PMID- 26672753 TI - Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels. AB - Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (alpha) and BK (alpha+beta1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (alpha) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (alpha+beta1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID- 26672754 TI - Foldameric probes for membrane interactions by induced beta-sheet folding. AB - Design strategies were devised for alpha/beta-peptide foldameric analogues of the antiangiogenic anginex with the goal of mimicking the diverse structural features from the unordered conformation to a folded beta-sheet in response to membrane interactions. Structure-activity relationships were investigated in the light of different beta-sheet folding levels. PMID- 26672755 TI - Partial PTEN deletion is linked to poor prognosis in breast cancer. AB - BACKGROUND: Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking. METHODS: We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe. RESULTS: PTEN deletions were detected in 19% of no special type, 9% of lobular, 4% of tubular cancers and 46% in carcinomas with medullary features. 98.7% of deletions were heterozygous and only 1.3% were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p=0.0054), high-grade (p<0.0001), high tumor cell proliferation (Ki67 Labeling Index; p<0.0001), and shortened overall survival (p=0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity; p<0.0001 each, and CCND1 amplification; p=0.0020). PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p=0.0430) and HER2 (p=0.0065). Remarkably the combined analysis of MYC, HER2, CCND1 and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p=0.0002). In addition, the particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy. CONCLUSION: PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells. PMID- 26672756 TI - Work environments and HIV prevention: a qualitative review and meta-synthesis of sex worker narratives. AB - BACKGROUND: Sex workers (SWs) experience a disproportionately high burden of HIV, with evidence indicating that complex and dynamic factors within work environments play a critical role in mitigating or producing HIV risks in sex work. In light of sweeping policy efforts to further criminalize sex work globally, coupled with emerging calls for structural responses situated in labour and human-rights frameworks, this meta-synthesis of the qualitative and ethnographic literature sought to examine SWs' narratives to elucidate the ways in which physical, social and policy features of diverse work environments influence SWs' agency to engage in HIV prevention. METHODS: We conducted a meta synthesis of qualitative and ethnographic studies published from 2008 to 2014 to elucidate SWs' narratives and lived experiences of the complex and nuanced ways in which physical, social, and policy features of indoor and outdoor work environments shape HIV prevention in the sex industry. RESULTS: Twenty-four qualitative and/or ethnographic studies were included in this meta-synthesis. SWs' narratives revealed the nuanced ways that physical, social, and policy features of work environments shaped HIV risk and interacted with macrostructural constraints (e.g., criminalization, stigma) and community determinants (e.g., sex worker empowerment initiatives) to shape SWs' agency in negotiating condom use. SWs' narratives revealed the ways in which the existence of occupational health and safety standards in indoor establishments, as well as protective practices of third parties (e.g., condom promotion) and other SWs/peers were critical ways of enhancing safety and sexual risk negotiation within indoor work environments. Additionally, working in settings where negative interactions with law enforcement were minimized (e.g., working in decriminalized contexts or environments in which peers/managers successfully deterred unjust policing practices) was critical for supporting SWs' agency to negotiate HIV prevention. CONCLUSIONS: Policy reforms to remove punitive approaches to sex work, ensure supportive workplace standards and policies, and foster SWs' ability to work collectively are recommended to foster the realization of SWs' health and human rights across diverse settings. Future qualitative and mixed-methods research is recommended to ensure that HIV policies and programmes are grounded in SWs' voices and realities, particularly in more under-represented regions such as Eastern Europe and Sub-Saharan Africa. PMID- 26672758 TI - Relation of retinal blood flow and retinal oxygen extraction during stimulation with diffuse luminance flicker. AB - Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 +/- 17.8%) and oxygen extraction (34.6 +/- 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown. PMID- 26672757 TI - Pathway-Based Genome-Wide Association Studies for Two Meat Production Traits in Simmental Cattle. AB - Most single nucleotide polymorphisms (SNPs) detected by genome-wide association studies (GWAS), explain only a small fraction of phenotypic variation. Pathway based GWAS were proposed to improve the proportion of genes for some human complex traits that could be explained by enriching a mass of SNPs within genetic groups. However, few attempts have been made to describe the quantitative traits in domestic animals. In this study, we used a dataset with approximately 7,700,000 SNPs from 807 Simmental cattle and analyzed live weight and longissimus muscle area using a modified pathway-based GWAS method to orthogonalise the highly linked SNPs within each gene using principal component analysis (PCA). As a result, of the 262 biological pathways of cattle collected from the KEGG database, the gamma aminobutyric acid (GABA)ergic synapse pathway and the non alcoholic fatty liver disease (NAFLD) pathway were significantly associated with the two traits analyzed. The GABAergic synapse pathway was biologically applicable to the traits analyzed because of its roles in feed intake and weight gain. The proposed method had high statistical power and a low false discovery rate, compared to those of the smallest P-value and SNP set enrichment analysis methods. PMID- 26672759 TI - Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis. AB - BACKGROUND: The purpose of this study was to investigate with neurophysiological and neuropsychological methods such as pupillometry, cognitive test and Hamilton Depression Rating Scale (HAM-D) the hypothesis of Central Nervous System (CNS) cholinergic involvement in patients with Myasthenia Gravis (MG). METHODS: Thirty two patients (32) with MG and a mean age of 51.1 +/- 17.2 volunteered to participate in this investigation, while thirty-three (33) healthy subjects with a mean age of 50.2 +/- 14.8 served as controls. All subjects underwent pupillometric measurements and performed the Wechsler Memory Scale (WMS) and HAM D. The pupillometric indices studied were: 1) latency for the onset of constriction (T1), 2) maximum constriction velocity (VCmax) and 3) maximum constriction acceleration (ACmax). RESULTS: T1 was found significantly increased by 21.7% (p < 0.05) in MG patients as compared to healthy subjects. Conversely, VCmax and ACmax were significantly decreased in MG patients by 33.3% (p < 0.05) and 43.5% (p < 0.05) respectively, as opposed to healthy subjects. Additionally, MG patients showed significantly decreased score in WMS by 41.6% (p < 0.05) as compared to healthy controls. No significant difference was found for HAM-D between the two groups. CONCLUSIONS: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction. PMID- 26672760 TI - Transbronchial Dissemination of Squamous Cell Lung Cancer. AB - We report a case of squamous cell lung cancer with transbronchial dissemination in a 73-year-old man. Bronchoscopic examination revealed multiple bronchial mucosal nodules that existed independently of one another. We reviewed 16 previous cases of endobronchial metastasis in lung cancer. All patients were men. Among the reports that described the smoking history, most patients were smokers (6/7), and the most frequent histological type of cancer was squamous cell carcinoma (11/17). Although hematogenous and lymphogenous routes have been reported as metastatic mechanisms, no previous cases involving transbronchial dissemination have been described. Transbronchial dissemination may be an alternative pathway of endobronchial metastasis. PMID- 26672762 TI - CyREST: Turbocharging Cytoscape Access for External Tools via a RESTful API. AB - As bioinformatic workflows become increasingly complex and involve multiple specialized tools, so does the difficulty of reliably reproducing those workflows. Cytoscape is a critical workflow component for executing network visualization, analysis, and publishing tasks, but it can be operated only manually via a point-and-click user interface. Consequently, Cytoscape-oriented tasks are laborious and often error prone, especially with multistep protocols involving many networks. In this paper, we present the new cyREST Cytoscape app and accompanying harmonization libraries. Together, they improve workflow reproducibility and researcher productivity by enabling popular languages (e.g., Python and R, JavaScript, and C#) and tools (e.g., IPython/Jupyter Notebook and RStudio) to directly define and query networks, and perform network analysis, layouts and renderings. We describe cyREST's API and overall construction, and present Python- and R-based examples that illustrate how Cytoscape can be integrated into large scale data analysis pipelines. cyREST is available in the Cytoscape app store (http://apps.cytoscape.org) where it has been downloaded over 1900 times since its release in late 2014. PMID- 26672761 TI - Renal denervation for the management of resistant hypertension. AB - Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients' adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the SymplicityTM system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID- 26672763 TI - Macroglossia Associated with Lymphangioma: Surgical Management of An Interesting Case. AB - Lymphangioma is considered as benign as well as a hamartomatous lesion of the lymphatic vessels that shows a marked predilection for the head and neck region. The most common site for intraoral lymphangiomas is the anterior two-thirds on the dorsal surface of tongue resulting in macroglossia. Such patients have a tendency of speech disturbances, poor oral hygiene, and bleeding from tongue following a trauma. A child with markedly enlarged tongue presents a unique challenge to the clinicians. Aesthetic, occlusal, functional and psychosocial problems may arise as a result of this condition. The indexed patient presented with an enlarged tongue. Wide excision of the lesion was done as a treatment. PMID- 26672764 TI - Melatonin inhibits AP-2beta/hTERT, NF-kappaB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells. AB - Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2beta and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-kappaB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2beta/hTERT, NF kappaB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment. PMID- 26672765 TI - Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis. AB - RNA-binding proteins (RBPs) play important roles in the regulation of gene expression through a variety of post-transcriptional mechanisms. The p53-induced RBP Wig-1 (Zmat3) binds RNA through its zinc finger domains and enhances stability of p53 and N-Myc mRNAs and decreases stability of FAS mRNA. To identify novel Wig-1-bound RNAs, we performed RNA-immunoprecipitation followed by high throughput sequencing (RIP-Seq) in HCT116 and Saos-2 cells. We identified 286 Wig 1-bound mRNAs common between the two cell lines. Sequence analysis revealed that AU-rich elements (AREs) are highly enriched in the 3'UTR of these Wig-1-bound mRNAs. Network enrichment analysis showed that Wig-1 preferentially binds mRNAs involved in cell cycle regulation. Moreover, we identified a 2D Wig-1 binding motif in HIF1A mRNA. Our findings confirm that Wig-1 is an ARE-BP that regulates cell cycle-related processes and provide a novel view of how Wig-1 may bind mRNA through a putative structural motif. We also significantly extend the repertoire of Wig-1 target mRNAs. Since Wig-1 is a transcriptional target of the tumor suppressor p53, these results have implications for our understanding of p53 dependent stress responses and tumor suppression. PMID- 26672766 TI - Inferring the progression of multifocal liver cancer from spatial and temporal genomic heterogeneity. AB - Multifocal tumors developed either as independent tumors or as intrahepatic metastases, are very common in primary liver cancer. However, their molecular pathogenesis remains elusive. Herein, a patient with synchronous two hepatocellular carcinoma (HCC, designated as HCC-A and HCC-B) and one intrahepatic cholangiocarcinoma (ICC), as well as two postoperative recurrent tumors, was enrolled. Multiregional whole-exome sequencing was applied to these tumors to delineate the clonality and heterogeneity. The three primary tumors showed almost no overlaps in mutations and copy number variations. Within each tumor, multiregional sequencing data showed varied intratumoral heterogeneity (21.6% in HCC-A, 20.4% in HCC-B, 53.2% in ICC). The mutational profile of two recurrent tumors showed obvious similarity with HCC-A (86.7% and 86.6% respectively), rather than others, indicating that they originated from HCC-A. The evolutionary history of the two recurrent tumors indicated that intrahepatic micro-metastasis could be an early event during HCC progression. Notably, FAT4 was the only gene mutated in two primary HCCs and the recurrences. Mutation prevalence screen and functional experiments showed that FAT4, harboring somatic coding mutations in 26.7% of HCC, could potently inhibit growth and invasion of HCC cells. In HCC patients, both FAT4 expression and FAT4 mutational status significantly correlated with patient prognosis. Together, our findings suggest that spatial and temporal dissection of genomic alterations during the progression of multifocal liver cancer may help to elucidate the basis for its dismal prognosis. FAT4 acts as a putative tumor suppressor that is frequently inactivated in human HCC. PMID- 26672769 TI - Organometallic Ru(II) Photosensitizers Derived from pi-Expansive Cyclometalating Ligands: Surprising Theranostic PDT Effects. AB - The purpose of the present study was to investigate the influence of pi-expansive cyclometalating ligands on the photophysical and photobiological properties of organometallic Ru(II) compounds. Four compounds with increasing pi conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, 1D and 2D (1)H NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5-8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC50 values = 1-2 MUM), in agreement with what has traditionally been observed for Ru(II) compounds derived from small C^N ligands. Surprisingly, the complex derived from the most pi-expansive cyclometalating ligand exhibited no cytotoxicity in the dark (EC50 > 300 MUM) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru(II) organometallic systems derived from pi-expansive cyclometalating ligands, such 4,9,16 triazadibenzo[a,c]napthacene (pbpn), represent the first class of potent light responsive Ru(II) cyclometalating agents with theranostic potential. PMID- 26672767 TI - High-throughput qRT-PCR validation of blood microRNAs in non-small cell lung cancer. AB - Validation of biomarkers is essential to advance the translational process to clinical application. Although there exists an increasing number of reports on small non-coding RNAs (microRNAs) as minimally-invasive markers from blood, serum or plasma, just a limited number is verified in follow-up studies. We used qRT PCR to evaluate a known miRNA signature measured from blood that allowed for separation between patients with non-small cell lung cancer (NSCLC), COPD and healthy controls.From the data of our previous microarray studies we selected a panel of 235 miRNAs related to lung cancer and COPD. We observed a high concordance between the AUC values of our initial microarray screening and the qRT-PCR data (correlation of 0.704, p < 10-16). Overall, 90.3% of markers were successfully validated. Among the top markers that were concordant between both studies we found hsa-miR-20b-5p, hsa-miR-20a-5p, hsa-miR-17-5p, and hsa-miR-106a 5p. The qRT-PCR analysis also confirmed that non-small cell lung cancer patients could be accurately differentiated from unaffected controls: a subset of five markers was sufficient to separate NSCLC patients from unaffected controls with accuracy of 94.5% (specificity and sensitivity of 98% and 91%). Beyond differentiation from controls, we also succeeded in separating NSCLC patients from patients with COPD. MiRNAs that were identified as relevant for the separation between lung cancer and COPD by both qRT-PCR and the array-based studies included hsa-miR-26a-5p, hsa-miR-328-3p and hsa-miR-1224-3p. Although for differentiation between NSCLC patients from COPD patients more markers were required, still high accuracy rates were obtained (5 markers: 78.8%; 10 markers: 83.9%; 50 markers: 87.6%). PMID- 26672770 TI - Complex Open Distal Femur Fracture Managed By Primary Autogenous Fibular Graft in Conjunction with DFLP- A Case Report. AB - Fractures of the distal part of the femur account for 7% of all femoral fractures. They are complex injuries that are difficult to manage; despite advances in technique and improved implants, treatment remains a challenge in many situations. An 18-year-old boy presented with an open fracture of the femur with bone loss. After initial emergency management, patient was given skeletal traction and kept on bohler braun splint. Regular antiseptic dressings of loosely stitched wound were done and intravenous antibiotics given. After 2 weeks when wound healed and twice cultures from wound site were negative, the fractured femur was stabilized with a dflp along with an autogenous free fibular graft and cortico-cancellous graft to bridge the bone defect. At one-year follow-up, fracture united with incorporation of free fibular graft. An autogenous free fibular graft in conjunction with a dflp is a viable option to manage bone defects in complicated supracondylar fractures of the femur. PMID- 26672768 TI - Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations. AB - In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies. PMID- 26672771 TI - Ocular hypertension and hypotony as determinates of outcomes in uveitis. AB - PURPOSE: To assess ocular hypertension (OHT) and hypotony as outcomes of uveitis in patients managed in a mid-Atlantic tertiary care center. METHODS: Retrospective, observational study of uveitis patients seen at the University of Virginia from 1984 to 2014. RESULTS: A total of 442 patients (582 eyes) with uveitis were identified and included in the study. The patient population was 57.0% female. Overall, 61.9% were Caucasian and 26.6% were African American. Mean age was 46.8 years. Overall, 11.5% of the eyes had OHT at initial visit, and 7.9% had OHT at final visit (P=0.035). For each additional decade of life, the odds that an eye had OHT were elevated by a factor of 1.15 (95% confidence interval [CI]: [1.02, 1.30], P=0.027) at initial visit and by a factor of 1.15 (95% CI: [1.00, 1.32], P=0.055) at final visit. The odds that an anterior uveitis eye had OHT were greater by a factor of 2.50 (95% CI: [1.22, 5.14], P=0.013) than the odds for a nonanterior uveitis eye at initial visit and greater by a factor of 2.61 (95% CI: [1.24, 5.50], P=0.011) at final visit. For each additional 0.5 logarithm of the minimum angle of resolution increase in initial visual acuity, the odds that an affected eye had OHT were elevated by a factor of 1.18 (95% CI: [1.00, 1.39], P=0.047) at initial visit and 1.23 (95% CI: [0.99, 1.54], P=0.065) at final visit. Overall, 21 of 582 eyes (3.6%) were hypotonous initially, while 24 of 582 eyes (4.1%) were hypotonous at final follow-up (P=0.631). CONCLUSION: OHT was associated with increasing age, anterior uveitis, and poor presenting visual acuity. Ocular hypotony was more common in anterior uveitis than in nonanterior uveitis. Fluctuations in intraocular pressure are an important cause of visual impairment in patients with uveitis. Careful monitoring of all uveitis patients, and especially those most at risk for fluctuations in intraocular pressure, can preserve vision and improve patient outcomes. PMID- 26672772 TI - Iatrogenic non-clostridial gas gangrene - a case report. AB - Skin and soft tissue infections of the lower limbs are quite common and can at times progress rapidly to become both limb and life-threatening infections. Muscular infections usually occur in areas of the body that have been compromised or injured by a foreign body, trauma, ischaemia, injection of illicit drugs, malignancy or surgery. Gas gangrene is one such limb-threatening infection. The gas-forming infection can be clostridial or non-clostridial. Clostridia are the main causative organism of the gas gangrene. Non-clostridial gas gangrene is a rare condition and is known to be associated with high mortality. Here, we report one such rare case where a middle-aged man succumbed to non-clostridial gas gangrene after he was administered an intramuscular injection. The case was registered as a suspicious death by the police and the body was subjected to medico legal autopsy. PMID- 26672773 TI - Antibiotic Prescribing Pattern in a Tertiary Level Neonatal Intensive Care Unit. AB - INTRODUCTION: Neonatal sepsis is a major cause of morbidity and mortality worldwide especially in developing countries, which justifies early diagnosis and prompt treatment with antibiotics. Antibiotics are the most frequently used medicines in Neonatal Intensive care units. Data regarding rational antibiotic use in neonates is very limited. Hence, it is essential that the antibiotic prescribing patterns be evaluated periodically for its rational use. Therefore, the present study been carried out to identify the prescribing patterns of antibiotics in neonatal intensive care unit of a tertiary care hospital, Western Maharashtra, India. MATERIALS AND METHODS: A prospective observational study was carried out for 6 months between April to September 2014. The data regarding patient demographics and antibiotic use was collected daily in a structured proforma. Collected data was subjected to statistical analysis. RESULTS: Out of total 528 neonates with male preponderance (62%), 370 received antibiotics. Mean gestational age and birth weight were 35+/-3.2 weeks and 2+/-0.7 kg respectively. Mean length of hospital stay was 14.26+/-15.36 days (range 1 to 136 days). A total of 1123 antibiotics were prescribed to 370 neonates. The majority of neonates (55.9%) received between 1-2 antibiotics, 37.3% had 3 to 5 antibiotics prescribed, while 6.7% neonates were prescribed more than 5 antibiotics. Number of antibiotics used had statistically significant inverse relationship with gestational age. Among antibiotics; Amikacin, Cefotaxime and Levofloxacin were the drugs most often prescribed. Amikacin and Cefotaxime were given more to term infants whereas other antibiotics like Levofloxacin, Pipercillin- tazobactam and Meropenem were prescribed more to preterm and outborn neonates. CONCLUSION: The use of a high number of antibiotics is a common practice. Although the indications for use of most antibiotics could be justified, the increased frequency of anbiotics use in some neonates was of concern. Guidelines for the use of antibiotics in neonates are required and larger studies are needed on this issue. PMID- 26672774 TI - Cycling Wheelchair Provides Enjoyable Pedaling Exercises with Increased Physiological Indexes. AB - The cycling wheelchair (CWC) can be used as a pedaling exercise machine. However, physiological indexes in the CWC at various pedaling rates and the difference between the CWC and the existing pedaling machines such as the portable ergometer (ERG) are unclear. The aim of this study was to measure physiological indexes in the CWC at various pedaling rates and compare the CWC to the ERG, focusing on psychological stress. The present non-randomized crossover study included ten healthy men (22.3 +/- 1.2 years) who performed pedaling exercise with the CWC and the ERG. Both experiments were composed of three pedaling exercise sessions (40, 60, and 80 rpm). Physiological indexes, consisting of oxygen consumption, heart rate, perceived breathlessness and leg fatigue, and salivary amylase activity (SAA), an index of psychological stress, were measured. The metabolic equivalent (METs) and the rate of change in SAA from rest to immediately after each pedaling session (DeltaSAA) were calculated. In the CWC, all physiological indexes significantly increased with pedaling rates. The METs were 2.2 +/- 0.3, 2.7 +/- 0.4, and 3.5 +/- 0.4 at 40, 60, and 80 rpm, respectively. In comparison between the CWC and the ERG, DeltaSAA was lower in the CWC than in the ERG at 60 and 80 rpm. Our results indicate that the CWC pedaling can provide low or moderate intensity exercises with adjusting pedaling rates and is less stressful than the ERG. Thus, the CWC is a useful pedaling machine to promote regular and enjoyable exercises. PMID- 26672775 TI - Multiparametric ultrasonography of the pediatric scrotum and in boys with undescended testes. AB - Due to its noninvasiveness and high resolving power, ultrasound examination is the examination of choice for the imaging of the structures of the pediatric scrotum. It allows to reveal changes impossible to find in the course of a clinical examination. Its significance has increased over the past few years due to the technological developments. The introduction of transducers with frequency of 10-17 MHz has improved the resolution of pediatric testes images as well as the resolution of the inguinal canals images, which has been of particular importance for the evaluation of undescended, retractile and abdominal testes. New diagnostic tools have also been introduced, such as 3D imaging or elastography, whose application has helped provide valuable additional information for the evaluation of pediatric testes, for treatment monitoring, and for post-surgical follow-up examinations. 3D imaging facilitates a more accurate evaluation of the location of an undescended testicle, testicular volume, and vascularization. Elastography may be used for the evaluation of focal lesions, post-ischemic lesions, unclear fluid spaces, undescended testes, and following orchiopexy. PMID- 26672776 TI - Australian court orders Nurofen's specific pain range off the shelves. PMID- 26672778 TI - Injury Rates in Age-Only Versus Age-and-Weight Playing Standard Conditions in American Youth Football. AB - BACKGROUND: American youth football leagues are typically structured using either age-only (AO) or age-and-weight (AW) playing standard conditions. These playing standard conditions group players by age in the former condition and by a combination of age and weight in the latter condition. However, no study has systematically compared injury risk between these 2 playing standards. PURPOSE: To compare injury rates between youth tackle football players in the AO and AW playing standard conditions. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Athletic trainers evaluated and recorded injuries at each practice and game during the 2012 and 2013 football seasons. Players (age, 5-14 years) were drawn from 13 recreational leagues across 6 states. The sample included 4092 athlete-seasons (AW, 2065; AO, 2027) from 210 teams (AW, 106; O, 104). Injury rate ratios (RRs) with 95% CIs were used to compare the playing standard conditions. Multivariate Poisson regression was used to estimate RRs adjusted for residual effects of age and clustering by team and league. There were 4 endpoints of interest: (1) any injury, (2) non-time loss (NTL) injuries only, (3) time loss (TL) injuries only, and (4) concussions only. RESULTS: Over 2 seasons, the cohort accumulated 1475 injuries and 142,536 athlete-exposures (AEs). The most common injuries were contusions (34.4%), ligament sprains (16.3%), concussions (9.6%), and muscle strains (7.8%). The overall injury rate for both playing standard conditions combined was 10.3 per 1000 AEs (95% CI, 9.8-10.9). The TL injury, NTL injury, and concussion rates in both playing standard conditions combined were 3.1, 7.2, and 1.0 per 1000 AEs, respectively. In multivariate Poisson regression models controlling for age, team, and league, no differences were found between playing standard conditions in the overall injury rate (RRoverall, 1.1; 95% CI, 0.4-2.6). Rates for the other 3 endpoints were also similar (RRNTL, 1.1 [95% CI, 0.4-3.0]; RRTL, 0.9 [95% CI, 0.4-1.9]; RRconcussion, 0.6 [95% CI, 0.3-1.4]). CONCLUSION: For the injury endpoints examined in this study, the injury rates were similar in the AO and AW playing standards. Future research should examine other policies, rules, and behavioral factors that may affect injury risk within youth football. PMID- 26672777 TI - Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance. AB - AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance. METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the (13)C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by chi(2) tests. RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city. CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions. PMID- 26672779 TI - Prostate cancer. PMID- 26672780 TI - Small organ, big reach. PMID- 26672781 TI - Screening: Diagnostic dilemma. PMID- 26672782 TI - Perspective: Enforce the clinical guidelines. PMID- 26672783 TI - Prognosis: Proportionate response. PMID- 26672784 TI - Treatment: When less is more. PMID- 26672785 TI - Metastasis: Resistance fighters. PMID- 26672786 TI - Microbiology: Inflammatory evidence. PMID- 26672787 TI - Q&A: Declan Murphy. PMID- 26672788 TI - Therapy: An immune one-two punch. PMID- 26672789 TI - Prostate cancer: 4 big questions. PMID- 26672790 TI - Root Glucosinolate Profiles for Screening of Radish (Raphanus sativus L.) Genetic Resources. AB - Radish (Raphanus sativus L.), a root vegetable, is rich in glucosinolates (GLs), which are beneficial secondary metabolites for human health. To investigate the genetic variations in GL content in radish roots and the relationship with other root phenotypes, we analyzed 71 accessions from 23 different countries for GLs using HPLC. The most abundant GL in radish roots was glucoraphasatin, a GL with four-carbon aliphatic side chain. The content of glucoraphasatin represented at least 84.5% of the total GL content. Indolyl GL represented only 3.1% of the total GL at its maximum. The principal component analysis of GL profiles with various root phenotypes showed that four different genotypes exist in the 71 accessions. Although no strong correlation with GL content and root phenotype was observed, the varied GL content levels demonstrate the genetic diversity of GL content, and the amount that GLs could be potentially improved by breeding in radishes. PMID- 26672791 TI - Correction to "Degradation of Methylene Blue Using Porous WO3, SiO2-WO3, and Their Au-Loaded Analogs: Adsorption and Photocatalytic Studies". PMID- 26672792 TI - Serum Protein Thiol Levels in Patients with Hospital-Acquired Acute Kidney Injury. AB - BACKGROUND/AIMS: This study aimed to examine antioxidants in patients with acute kidney injury (AKI) and determine whether serum protein thiol levels are associated with all-cause 90-day mortality in patients with hospital-acquired AKI. METHODS: According to the RIFLE criteria, 160 patients with hospital acquired AKI were enrolled in our prospective cohort study. As controls, 72 critically ill patients without AKI and 72 age and sex-matched healthy subjects were also recruited. Serum protein thiol levels were analyzed in relation to all cause mortality of patients with AKI. RESULTS: Serum protein thiol levels in AKI patients were lower than those in healthy people (p=0.010). Protein thiol levels showed a weak but significant positive correlation with serum albumin levels. The 90-day overall mortality rate was higher in AKI patients with high serum protein thiol levels than in those with low levels (p=0.032 by log rank test). In multivariate analysis (Cox regression), serum protein thiol levels (p=0.031) were independently associated with 90-day overall mortality after adjustment for age, sex, sepsis, and the Acute Physiology and Chronic Health Evaluation II score. CONCLUSIONS: Patients with hospital-acquired AKI have remarkably low serum protein thiol levels. Elevated protein thiol levels are associated with 90-day overall mortality in hospital-acquired AKI. PMID- 26672794 TI - Effects of Capillary Forces on a Hydrogel Sphere Pressed against a Surface. AB - A theoretical treatment is provided for effects of capillary forces on a hemispherically shaped hydrogel sample pressed against a solid hydrophilic surface. It is pointed out that the adhesion of a hydrogel to a surface resulting from capillary forces is different from that of a nonporous solid because of the porous nature of the hydrogel. Because of this, the Laplace pressure subtracts from the osmotic pressure inside the gel. For neutral gels, it can exceed the osmotic pressure, causing the gel to deswell. For charged gels, since the counterions inside the gel generally provide much higher osmotic pressure than that due to monomers alone (which is the only source of osmotic pressure in neutral hydrogels), the Laplace pressure is less likely to make the gel deswell. The Laplace pressure can, however, be large enough to deswell asperities (due to surface roughness) on the gel surface, increasing the contact area. This could result in an increase in the friction and ionic electrical conductivity between the gel and the surface (if the surface is an electrical conductor). PMID- 26672793 TI - Is Specialized Integrated Treatment for Comorbid Anxiety, Depression and Alcohol Dependence Better than Treatment as Usual in a Public Hospital Setting? AB - AIM: To assess the effectiveness of a 12 week specialized, integrated intervention for alcohol dependence with comorbid anxiety and/or mood disorder using a randomized design in an outpatient hospital setting. METHODS: Out of 86 patients meeting the inclusion criteria for alcohol dependence with suspicion of comorbid anxiety and/or depressive disorder, 57 completed a 3-week stabilization period (abstinence or significantly reduced consumption). Of these patients, 37 (65%) met a formal diagnostic assessment of an anxiety and/or depressive disorder and were randomized to either (a) integrated intervention (cognitive behavioural therapy) for alcohol, anxiety and/or depression, or (b) usual counselling care for alcohol problems. RESULTS: Intention-to-treat analyses revealed a beneficial treatment effect of integrated treatment relative to usual counselling care for the number of days to relapse (chi(2) = 6.42, P < 0.05) and lapse (chi(2) = 10.73, P < 0.01). In addition, there was a significant interaction effect of treatment and time for percentage days of abstinence (P < 0.05). For heavy drinking days, the treatment effect was mediated by changes in DASS anxiety (P < 0.05). There were no significant treatment interaction effects for DASS depression or anxiety symptoms. CONCLUSIONS: These results provide support for integrated care in improving drinking outcomes for patients with alcohol dependence and comorbid depression/anxiety disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01941693. PMID- 26672795 TI - An Effective Approach to Improving Cadmium Telluride (111)A Surface by Molecular Beam-Epitaxy Growth of Tellurium Monolayer. AB - The surface cleansing treatment of non-natural cleavage planes of semiconductors is usually performed in vacuum using ion sputtering and subsequent annealing. In this Research Article, we report on the evolution of surface atomic structure caused by different ways of surface treatment as monitored by in situ core-level photoemission measurements of Cd-4d and Te-4d atomic levels and reflection high energy electron diffraction (RHEED). Sputtering of surface increases the density of the dangling bonds by 50%. This feature and the less than ideal ordering can be detrimental to device applications. An effective approach is employed to improve the quality of this surface. One monolayer (ML) of Te grown by the method of molecular beam epitaxy (MBE) on the target surface with heating at 300 degrees C effectively improves the surface quality as evidenced by the improved sharpness of RHEED pattern and a reduced diffuse background in the spectra measured by high-resolution ultraviolet photoemission spectroscopy (HRUPS). Calculations have been performed for various atomic geometries by employing first principles geometry optimization. In conjunction with an analysis of the core level component intensities in terms the layer-attenuation model, we propose a "vacancy site" model of the modified 1 ML-Te/CdTe(111)A (2 * 2) surface. PMID- 26672796 TI - Prediction of difficult intubation with direct laryngoscopy winded up in quicksand: how can we get out of it? PMID- 26672797 TI - Mechanical resuscitation devices under special circumstances in the out of hospital setting. PMID- 26672798 TI - DPP-4 inhibitors, heart failure and type 2 diabetes: all eyes on safety. AB - Epidemiological analyses have clearly outlined the association between heart failure (HF) and diabetes (DM). HF patients with concomitant DM show a further increase in morbidity and mortality due to coexistence of several mechanisms including disturbed neurohormonal axis as well as structural and functional abnormalities occurring in the diabetic myocardium. Although several studies have shown that poor glycemic control-as indicated by HbA1c levels-may be associated with an increased risk of HF, this issue remains poorly understood and further evidence is required to show unequivocal benefits of this approach. In the attempt to explore the effects of new anti-hyperglycemic therapies, randomized trials have shown that some glucose-lowering drugs-thought not affecting cardiovascular (CV) death or ischemic complications-might significantly increase the risk of HF-hospitalizations in DM patients. Specifically, the use of dipeptidyl-peptidase-4 (DDP-4) inhibitors (DPP-4i) has recently raised a major safety concern owing to an increase of HF hospitalizations in SAVOR-TIMI 53 trial. In contrast with these findings, the more recent TECOS study as well as new TECOS sub-analyses presented at the last ESC Congress-have yielded to the conclusion that the DPP-4i sitagliptin is not associated with any sort of HF risk. Therefore, increased risk of HF hospitalizations does not seem to be a class effect of DPP-4i. The present article critically discusses available evidence concerning DPP-4i and risk of HF in patients with type 2 diabetes (T2D). The use of DPP-4i in combination therapy is also discussed, in light of the recent EMPA-REG trial. PMID- 26672799 TI - Corneal Penetrating Elastin-Like Polypeptide Carriers. AB - PURPOSE: Elastin-like polypeptide (ELP) is a bioengineered protein widely applied as a drug carrier due to its biocompatibility and amenability to modification with cell-penetrating peptides (CPPs) and therapeutic agents. The purpose of this study was to determine whether topically applied ELP or CPP-fused ELPs penetrate the corneal barrier. METHODS: In vitro binding and cytotoxicity to human corneal epithelial (HCE) cells were determined for ELP or CPP-ELPs. Corneal binding, clearance, and penetration were assessed in a rabbit model following topical application of the fluorescently labeled proteins by quantitative fluorescence imaging and histology. RESULTS: ELP bound to HCE cells in vitro, and binding/uptake was enhanced 2- to 3-fold by the addition of CPPs. When applied topically to rabbit eyes, ELP accumulated in the cornea at levels 7.4-fold higher than did an equivalent dose of immunoglobulin G. Both ELP and a CPP-ELP penetrated the corneal epithelium and were detectable in the stroma. Addition of CPPs to ELP, however, did not significantly enhance corneal uptake or penetration in vivo relative to ELP alone. The polypeptides cleared from the cornea over a period of 20-30 min after application, after which cornea levels reached a steady state of 15-30 MUg/mL for up to 3 h. CONCLUSIONS: The ELP drug carrier can penetrate the corneal epithelium and accumulate in the stroma. Given its amenability for fusion to multiple types of therapeutic agents, ELP has the potential to serve as a drug carrier for topical ocular applications. PMID- 26672801 TI - Fully Tunable Silicon Nanowire Arrays Fabricated by Soft Nanoparticle Templating. AB - We demonstrate a fabrication breakthrough to produce large-area arrays of vertically aligned silicon nanowires (VA-SiNWs) with full tunability of the geometry of the single nanowires and of the whole array, paving the way toward advanced programmable designs of nanowire platforms. At the core of our fabrication route, termed "Soft Nanoparticle Templating", is the conversion of gradually compressed self-assembled monolayers of soft nanoparticles (microgels) at a water-oil interface into customized lithographical masks to create VA-SiNW arrays by means of metal-assisted chemical etching (MACE). This combination of bottom-up and top-down techniques affords excellent control of nanowire etching site locations, enabling independent control of nanowire spacing, diameter and height in a single fabrication route. We demonstrate the fabrication of centimeter-scale two-dimensional gradient photonic crystals exhibiting continuously varying structural colors across the entire visible spectrum on a single silicon substrate, and the formation of tunable optical cavities supported by the VA-SiNWs, as unambiguously demonstrated through numerical simulations. Finally, Soft Nanoparticle Templating is combined with optical lithography to create hierarchical and programmable VA-SiNW patterns. PMID- 26672800 TI - Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non Invasive Marker for Liver Cirrhosis. AB - INTRODUCTION: Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. AIM: To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. MATERIALS AND METHODS: Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (10(9)/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. RESULTS: APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. CONCLUSION: APRI could identify cirrhosis with high degree of accuracy in the studied patients. PMID- 26672802 TI - Standards of the Polish Ultrasound Society - update. Spleen examination. AB - Ultrasound scan of the spleen is an integral part of the overall abdominal examination. Due to its anatomical position, physical examination of the spleen is frequently supplemented with an ultrasound which plays a special role in the differential diagnostics of splenic diseases and facilitates the determination of further diagnostic and therapeutic procedures. Similarly to other types of ultrasound scans, the examiner should be familiar with all significant clinical information as well as results of examinations and tests conducted so far. This enables to narrow the scope of search for etiological factors and indicate specific disease entities in the findings as well as allows for accurate assessment of coexistent pathologies. The article presents the standards of the Polish Ultrasound Society concerning the apparatus, preparation for the examination, technique and description of the findings. The authors discuss the normal anatomy of the spleen and the most common pathologies ranging from splenomegaly to splenic traumas. The indications for the contrast-enhanced ultrasound and characteristic patterns of enhancement of individual focal lesions are presented. This article is supplemented with photographic documentation, which provides images of the discussed lesions. The ultrasound examination, if carried out in compliance with current standards, allows for accurate interpretation of detected changes. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011) and updated with the current knowledge. PMID- 26672803 TI - Healthcare provider contact for children with symptoms of sleep-disordered breathing: a population survey. AB - BACKGROUND: Symptoms of sleep-disordered breathing in children, such as frequent snoring, apnoea and choking, may lead to health problems if untreated. The caregiver's level of awareness of these symptoms has been poorly studied. This study aimed to study healthcare provider contact related to sleep-disordered breathing symptoms in a population of children aged 0-11 years. METHODS: A total of 1320 children were randomly selected from a national database that included all children living in Sweden. Caregivers answered a questionnaire about sleep disordered breathing symptoms during the last month and healthcare provider contact related to these symptoms. RESULTS: A total of 754 answers were received. The prevalence of sleep-disordered breathing symptoms was 4.8 per cent. Of this subgroup, 69 per cent had not been in contact with a healthcare provider regarding their symptoms. CONCLUSION: This study shows that sleep-disordered breathing in children is underestimated and that there is a need to increase caregiver and healthcare provider awareness of sleep-disordered breathing in children. PMID- 26672804 TI - Ephrin-A5 Is Required for Optimal Fertility and a Complete Ovulatory Response to Gonadotropins in the Female Mouse. AB - Follicle growth and ovulation involve the coordinated expression of many genes, driven by FSH and LH. Reports indicate that Eph receptors and ephrins are expressed in the ovary, suggesting roles in follicle growth and/or ovulation. We previously reported FSH-induced expression of ephrin-A5 (EFNA5) and 4 of its cognate Eph receptors in mouse granulosa cells. We now report that female mice lacking EFNA5 are subfertile, exhibit a compromised response to LH, and display abnormal ovarian histology after superovulation. Efna5(-/-) females litters were 40% smaller than controls, although no difference in litter frequency was detected. The ovarian response to superovulation was also compromised in Efna5(-/ ) females, with 37% fewer oocytes ovulated than controls. These results corresponded with a reduction in ovarian mRNA levels of several LH-responsive genes, including Pgr, Ptgs2, Tnfaip6, Ereg, Btc, and Adamts4, suggesting that Efna5(-/-) ovaries exhibit a partially attenuated response to LH. Histopathological analysis indicated that superovulated Efna5(-/-) females exhibited numerous ovarian defects, including intraovarian release of cumulus oocyte complexes, increased incidence of oocytes trapped within luteinized follicles, granulosa cell and follicular fluid emboli, fibrin thrombi, and interstitial hemorrhage. In addition, adult Efna5(-/-) ovaries exhibited a 4-fold increase in multioocyte follicles compared with controls, although no difference was detected in 3-week-old mice, suggesting the possibility of follicle merging. Our observations indicate that loss of EFNA5 in female mice results in subfertility and imply that Eph-ephrin signaling may also play a previously unidentified role in the regulation of fertility in women. PMID- 26672805 TI - Moderate Exercise Prevents Functional Remodeling of the Anterior Pituitary Gland in Diet-Induced Insulin Resistance in Rats: Role of Oxidative Stress and Autophagy. AB - A sustained elevation of glucocorticoid production, associated with the establishment of insulin resistance (IR) could add to the deleterious effects of the IR state. The aim of this study is to analyze the consequences of long-term feeding with a sucrose-rich diet (SRD) on Pomc/ACTH production, define the underlying cellular processes, and determine the effects of moderate exercise (ME) on these parameters. Animals fed a standard chow with or without 30% sucrose in the drinking water were subjected to ME. Circulating hormone levels were determined, and pituitary tissues were processed and analyzed by immunobloting and quantitative real-time PCR. Parameters of oxidative stress (OxS), endoplasmic reticulum stress, and autophagy were also determined. Rats fed SRD developed a decrease in pituitary Pomc/ACTH expression levels, increased expression of antioxidant enzymes, and induction of endoplasmic reticulum stress and autophagy. ME prevented pituitary dysfunction as well as induction of antioxidant enzymes and autophagy. Reporter assays were performed in AtT-20 corticotroph cells incubated in the presence of palmitic acid. Pomc transcription was inhibited by palmitic acid-dependent induction of OxS and autophagy, as judged by the effect of activators and inhibitors of both processes. Long-term feeding with SRD triggers the generation of OxS and autophagy in the pituitary gland, which could lead to a decline in Pomc/ACTH/glucocorticoid production. These effects could be attributed to an increase in fatty acids availability to the pituitary gland. ME was able to prevent these alterations, suggesting additional beneficial effects of ME as a therapeutic strategy in the management of IR. PMID- 26672807 TI - Dynamical Properties of N-Isopropylacrylamide Molecule in Water Revealed by (1)H NMR Studies. AB - The hydration of alkyl-amide molecules in water is very important for understanding their solubility in water, which related to the phase behavior of polyamides including protein molecules in water. The (1)H NMR signals of N isopropylacrylamide (NIPA) in water were investigated for the purpose to reveal the hydration properties of NIPA in the aqueous HCl solutions, which change the phase behavior of aqueous NIPA solutions with HCl concentration as reported previously (J. Phys. Chem. B 2011, 115, 12905-12910). The following observations were revealed by the present studies. (1) The spin-spin coupling of the amide proton with the methyne proton in the HCl solution was observed when a half width of amide peak (~Deltanu) was less than about 10 Hz, but it was not when Deltanu was greater than 10 Hz. (2) The Deltanu value of amide proton increased with an increase in a mole ratio of H2O to NIPA (rH2O) or with enlargement of the protonated hydration shell, which reduced the energy gap of the cis- and trans conformations. (3) The Deltanu value of H2O and its rH2O dependence in the 3 M HCl solution changed drastically between rH2O = 4.0 and 4.7, in which the hydrophilic hydration shell neighboring the amide extended to form the hydrophobic hydration shell. (4) The Deltanu of methyl proton decreased monotonously with rH2O. This indicates an increase of the rotational mobility of methyl groups in the hydration shell. These results indicate that the elongating lifetime of cis-conformation of amide coupled with the shortened lifetime of double bonding C-N in amide induces the amide-methyne spin-spin-coupling transition and that the cationic state of amide stabilizes the hydrophobic hydration to induce the rotational free motion of amide C-N and the methyl groups. PMID- 26672806 TI - Ghrelin Promotes Functional Angiogenesis in a Mouse Model of Critical Limb Ischemia Through Activation of Proangiogenic MicroRNAs. AB - Current therapeutic strategies for the treatment of critical limb ischemia (CLI) have only limited success. Recent in vitro evidence in the literature, using cell lines, proposes that the peptide hormone ghrelin may have angiogenic properties. In this study, we aim to investigate if ghrelin could promote postischemic angiogenesis in a mouse model of CLI and, further, identify the mechanistic pathway(s) that underpin ghrelin's proangiogenic properties. CLI was induced in male CD1 mice by femoral artery ligation. Animals were then randomized to receive either vehicle or acylated ghrelin (150 MUg/kg sc) for 14 consecutive days. Subsequently, synchrotron radiation microangiography was used to assess hindlimb perfusion. Subsequent tissue samples were collected for molecular and histological analysis. Ghrelin treatment markedly improved limb perfusion by promoting the generation of new capillaries and arterioles (internal diameter less than 50 MUm) within the ischemic hindlimb that were both structurally and functionally normal; evident by robust endothelium-dependent vasodilatory responses to acetylcholine. Molecular analysis revealed that ghrelin's angiogenic properties were linked to activation of prosurvival Akt/vascular endothelial growth factor/Bcl-2 signaling cascade, thus reducing the apoptotic cell death and subsequent fibrosis. Further, ghrelin treatment activated proangiogenic (miR-126 and miR-132) and antifibrotic (miR-30a) microRNAs (miRs) while inhibiting antiangiogenic (miR-92a and miR-206) miRs. Importantly, in vitro knockdown of key proangiogenic miRs (miR-126 and miR-132) inhibited the angiogenic potential of ghrelin. These results therefore suggest that clinical use of ghrelin for the early treatment of CLI may be a promising and potent inducer of reparative vascularization through modulation of key molecular factors. PMID- 26672808 TI - The Effect of Child Distress on Accommodation of Anxiety: Relations With Maternal Beliefs, Empathy, and Anxiety. AB - Little is known about the influence of child behaviors on accommodation of anxiety and how accommodation relates to other parent factors. The present study examined the comparative effect of high and low levels of child distress on mother-reported accommodation, mother factors in relation to accommodation, and moderators of the relation between accommodation and child distress. Maternal perceptions of accommodation were measured by vignettes depicting youth exhibiting high or low levels of distress in anxiety-provoking situations that elicited social anxiety, generalized anxiety, or separation anxiety in a sample of 7- to 17-year-old youth with anxiety disorders (N = 70, M = 11.66, 47.1% male). Findings indicated an effect of child distress on mother-reported accommodation of youth anxiety, such that mothers reported more overall accommodation under conditions of high child distress; situation-level analyses revealed this effect for social and generalized anxiety situations. Furthermore, an association was found between greater mother-reported accommodation and more negative beliefs about their child's experience of anxiety, which held across situations. Maternal empathy moderated the relation between overall accommodation and child distress. Maternal anxiety also moderated the relation between accommodation and child distress, with results varying based on situation type. Findings, consistent with theory, indicate a relation between child distress and mother-reported accommodation and suggest that maternal beliefs about anxiety are an important treatment target. High maternal empathy may be related to a greater degree of adaptability in response to child behaviors, whereas maternal anxiety may be linked with less adaptive responses to child behaviors. PMID- 26672809 TI - Straight ladder inclined angle in a field environment: the relationship among actual angle, method of set-up and knowledge. AB - Ladder inclined angle is a critical factor that could lead to a slip at the base of portable straight ladders, a major cause of falls from heights. Despite several methods established to help workers achieve the recommended 75.5 degrees angle for ladder set-up, it remains unclear if these methods are used in practice. This study explored ladder set-up behaviours in a field environment. Professional installers of a company in the cable and other pay TV industry were observed for ladder set-up at their worksites. The results showed that the actual angles of 265 ladder set-ups by 67 participants averaged 67.3 degrees with a standard deviation of 3.22 degrees . Although all the participants had training on recommended ladder set-up methods, only 3 out of 67 participants applied these methods in their daily work and even they failed to achieve the desired 75.5 degrees angle. Therefore, ladder set-up remains problematic in real-world situations. Practitioner Summary: Professional installers of a cable company were observed for portable straight ladder set-up at their worksites. The ladder inclined angle averaged 67.3 degrees with a standard deviation of 3.22 degrees , while the recommended angle is 75.5 degrees . Only a few participants used the methods that they learned during training in their daily work. PMID- 26672810 TI - The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane and I. Sudol Szopinska, K. Zaniewicz-Kaniewska, A. Warczynska, G. Matuszewska, F. Saied, W. Kunisz The pathogenesis of rheumatoid arthritis in radiological studies. Part II: Imaging studies in rheumatoid arthritis. PMID- 26672811 TI - Surgical mortality in patients more than 80 years of age. AB - INTRODUCTION: Patients aged >80 years account for a considerable proportion of the population admitted to hospital under general surgeons. We aimed to establish the prevalence of mortality in patients aged >80 years who underwent emergency general, vascular and urological surgery within a 13-month period at a large teaching hospital in the UK. MATERIALS AND METHODS: A retrospective analysis was carried out of all patients aged >=80 years admitted on acute on-call emergency under general, vascular or urological surgeons. Patient demographics (including comorbidities and sex) were recorded. American Society of Anesthesiologists scores were reviewed from anaesthetic records. The outcome measure was 30-day mortality for those who had undergone emergency general, vascular or urological surgery. RESULTS: A total of 4,069 patients were admitted under general, vascular and urological surgeons during the study period. Of these patients, 521 were aged >80 years. Sixty-three patients underwent emergency surgery and 12 died <30 days after surgery (mortality = 19%). The most common procedure was laparotomy (20 cases). The most common co-morbidity was cardiac disease, which included hypertension, ischaemic heart disease, and hypercholesterolemia. A considerable proportion of patients also had malignant disease and arthritis. CONCLUSIONS: The present study suggests that emergency surgery should not be denied to subjects aged >80 years based on age alone. Mortality varies according to the type of emergency procedure. Mortality was highest after laparotomy and vascular surgery whereas, for more routine procedures such as hernia repair and abscess drainage, survival was almost 100% after 30 days. PMID- 26672845 TI - Co-Incidence or Co-Existence? Acute Lymphoblastic Leukaemia in HbE-alpha Thalassaemia: A Case Report with Review of Literature. AB - Haemoglobin E (HbE) is a Haemoglobin variant that commonly occurs in many places in Asia. As beta thalassaemia and alpha thalassaemia also occur in the same regions, the co-inheritance of these conditions leads to various phenotypic forms. HbE alpha thalassaemia is less common and of a milder phenotype than HbE beta thalassaemia. Though malignancies are one of the complications in thalassaemia, occurrence of leukaemia is a rare event. Here we present a case of a two-year-old male child co-presenting with pre B acute lymphoblastic leukaemia (ALL) with MLL rearrangement and HbE alpha thalassaemia. The child is on remission 12 months post-therapy with standard ALL high risk protocol with no minimal residual disease (MRD). Haematological and oncological conditions coexisting at presentation is a challenge to therapy. This case is described for its rarity. Informed consent has been obtained from the parents. PMID- 26672846 TI - Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice. AB - BACKGROUND: Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS: We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS: In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [+/-SD] age, 81.0+/-6.1 years vs. 70.2+/-10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS: The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.). PMID- 26672847 TI - IMAGES IN CLINICAL MEDICINE. Scrub Typhus. PMID- 26672848 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 39-2015. A 22-Year-Old Man with Hypoxemia and Shock. PMID- 26672849 TI - Cancer Screening in Unprovoked Venous Thromboembolism. PMID- 26672850 TI - Cancer Screening in Unprovoked Venous Thromboembolism. PMID- 26672851 TI - Cancer Screening in Unprovoked Venous Thromboembolism. PMID- 26672852 TI - Cancer Screening in Unprovoked Venous Thromboembolism. PMID- 26672853 TI - Elective versus Therapeutic Neck Dissection in Oral Cancer. PMID- 26672854 TI - Elective versus Therapeutic Neck Dissection in Oral Cancer. PMID- 26672855 TI - Elective versus Therapeutic Neck Dissection in Oral Cancer. PMID- 26672856 TI - Elective versus Therapeutic Neck Dissection in Oral Cancer. PMID- 26672857 TI - Sitagliptin and Cardiovascular Outcomes in Type 2 Diabetes. PMID- 26672858 TI - Sitagliptin and Cardiovascular Outcomes in Type 2 Diabetes. PMID- 26672859 TI - Sitagliptin and Cardiovascular Outcomes in Type 2 Diabetes. PMID- 26672860 TI - Sitagliptin and Cardiovascular Outcomes in Type 2 Diabetes. PMID- 26672861 TI - Intrapartum Fetal ECG ST-Segment Analysis. PMID- 26672862 TI - Intrapartum Fetal ECG ST-Segment Analysis. PMID- 26672863 TI - Electrolyte and Acid-Base Disturbances in Diabetes Mellitus. PMID- 26672864 TI - Electrolyte and Acid-Base Disturbances in Diabetes Mellitus. PMID- 26672865 TI - Electrolyte and Acid-Base Disturbances in Diabetes Mellitus. PMID- 26672866 TI - Electrolyte and Acid-Base Disturbances in Diabetes Mellitus. PMID- 26672867 TI - Electrolyte and Acid-Base Disturbances in Diabetes Mellitus. PMID- 26672868 TI - Examination of the Retina. PMID- 26672869 TI - Examination of the Retina. PMID- 26672870 TI - Post-Ebola Signs and Symptoms in U.S. Survivors. PMID- 26672871 TI - IMAGES IN CLINICAL MEDICINE. Achalasia with Megaesophagus. PMID- 26672872 TI - Martial Art Training and Cognitive Performance in Middle-Aged Adults. AB - Cognitive performance includes the processes of attention, memory, processing speed, and executive functioning, which typically declines with aging. Previous research has demonstrated that aerobic and resistance exercise improves cognitive performance immediately following exercise. However, there is limited research examining the effect that a cognitively complex exercise such as martial art training has on these cognitive processes. Our study compared the acute effects of 2 types of martial art training to aerobic exercise on cognitive performance in middle-aged adults. We utilized a repeated measures design with the order of the 3 exercise conditions randomly assigned and counterbalanced. Ten recreational middle-aged martial artists (mean age = 53.5 +/- 8.6 years) participated in 3 treatment conditions: a typical martial art class, an atypical martial art class, and a one-hour walk at a self-selected speed. Cognitive performance was assessed by the Stroop Color and Word test. While all 3 exercise conditions improved attention and processing speed, only the 2 martial art conditions improved the highest order of cognitive performance, executive function. The effect of the 2 martial art conditions on executive function was not different. The improvement in executive function may be due to the increased cortical demand required by the more complex, coordinated motor tasks of martial art exercise compared to the more repetitive actions of walking. PMID- 26672888 TI - Answer to the question from page 356. PMID- 26672873 TI - Left atrial strain as evaluated by two-dimensional speckle tracking predicts left atrial appendage dysfunction in patients with acute ischemic stroke. AB - BACKGROUND: Left atrial appendage (LAA) dysfunction predisposes patients with atrial fibrillation (AF) to cardioembolic stroke. Two-dimensional (2D) speckle tracking was reported to be useful for evaluating left atrial (LA) regional function, as well as left ventricular function. However, it remains unclear whether 2D speckle tracking is useful for evaluating LAA dysfunction. Therefore, we investigated whether decreased LA strain may predict LAA dysfunction and thrombus formation in patients with acute ischemic stroke. METHODS: We performed transthoracic and transesophageal echocardiography in 120 patients (83 males, mean age 72 +/- 11 years) within 7 days of onset of an acute ischemic stroke. Longitudinal LA strain was evaluated using 2D speckle tracking imaging at each LA segment, and peak systolic strain was calculated by averaging the results for each segment. RESULTS: Forty-eight patients had LAA dysfunction as defined by the presence of LAA thrombus and/or severe spontaneous echo contrast. LA peak systolic strain was significantly decreased in patients with LAA dysfunction compared to those without (32.3 +/- 13.7% vs. 12.1 +/- 7.2%, p < 0.0001). LA peak systolic strain was significantly correlated with LAA emptying flow velocity (r = 0.693, p < 0.0001). The optimum LA peak systolic strain cut-off value for predicting LAA dysfunction was 19%. Multivariate logistic regression analysis showed that LA peak systolic strain was an independent predictor of LAA dysfunction (odds ratio 0.059, 95% confidence interval 0.018-0.146; p < 0.0001). CONCLUSION: Decreased LA peak systolic strain was independently associated with LAA dysfunction in patients with acute ischemic stroke. PMID- 26672889 TI - Fatal Case of Pericardial Effusion Due to Myroides Odoratus: A Rare Case Report. AB - Myroides spp., previously known as Flavobacterium odoratum, are rare clinical isolates and are often considered non-pathogenic. Natural habitat includes soil, fresh and marine waters, in foods and in sewage treatment plants. We present an unusual case of fatal pericardial effusion due to Myroides odoratus in a patient suffering from chronic kidney disease and undergoing maintenance haemodialysis. This case is presented to show the increasing incidence of rare isolates causing localized and systemic infections and due to their high intrinsic resistance to many antibiotics they can be fatal. Thus isolation of these pathogens is of great clinical importance. PMID- 26672891 TI - Hamartomatous Tumors in the Gastrointestinal Tract. AB - BACKGROUND: Digestive hamartomatous polyps are a rare entity. They may be sporadic (solitary Peutz-Jeghers polyp or solitary juvenile polyp) or reveal genetic predisposition like Peutz-Jeghers syndrome, juvenile polyposis or Cowden disease. SUMMARY: Diagnosis is based on personal and family history and on clinical data including physical signs (in particular dermatological), endoscopic findings (the number of polyps) and histological features of the polyps. The risk of complications and of digestive and extra-digestive cancers may be high, especially in case of genetic predisposition syndromes, and requires multidisciplinary management of the patients (oncogenetic counseling, gastroenterologist, pathologist, dermatologist, gynecologist and endocrinologist). Endoscopic evaluation is very helpful to establish the current situation, to perform polypectomy and to allow for good histological examination of the polyps, whose degeneration has been exceptionally described. The recent development of new molecular techniques (next-generation DNA sequencing) allows for rapid multiple gene sequencing and facilitates diagnosis. KEY MESSAGE: Discovery of a hamartomatous polyp requires a rigorous work-up which should be performed by a multidisciplinary team, including a genetic oncologist, experienced in this pathology. PRACTICAL IMPLICATIONS: The diagnostic procedure in hamartomatous polyps should be based on the number of polyps identified during endoscopy (solitary versus multiple) and on their histological characteristics. The clinical examination must search for mucosal and skin lesions. If a polyposis syndrome is identified, oncogenetic consultation is necessary in order to define screening modalities for family members, aiming at preventing cancer development. Endoscopic resection (polypectomy) of the lesions may prevent complications like bleeding and degeneration and also diminish the risk of surgery and subsequent short bowel syndrome. PMID- 26672890 TI - ESHOL study reanalysis: All-cause mortality considered by competing risks and time-dependent covariates for renal transplantation. AB - BACKGROUND: The ESHOL study showed that post-dilution online haemodiafiltration (OL-HDF) reduces all-cause mortality versus haemodialysis. However, during the observation period, 355 patients prematurely completed the study and, according to the study design, these patients were censored at the time of premature termination. METHODS: The aim of this study was to investigate the outcome of patients who discontinued the study. RESULTS: During follow-up, 207 patients died while under treatment and 47 patients died after discontinuation of the study. Compared with patients maintained on haemodialysis, those randomised to OL-HDF had lower all-cause mortality (12.4 versus 9.46 per 100 patient-years, hazard ratio and 95%CI: 0.76; [0.59-0.98], P= 0.031). For all-cause mortality by time dependent covariates and competing risks for transplantation, the time-dependent Cox analysis showed very similar results to the main analysis with a hazard ratio of 0.77 (0.60-0.99, P= 0.043). CONCLUSION: The results of this analysis of the ESHOL trial confirm that post-dilution OL-HDF reduces all-cause mortality versus haemodialysis in prevalent patients. The original results of the ESHOL study, which censored patients discontinuing the study for any reason, were confirmed in the present ITT population without censures and when all-cause mortality was considered by time-dependent and competing risks for transplantation. PMID- 26672893 TI - BGRcast: A Disease Forecast Model to Support Decision-making for Chemical Sprays to Control Bacterial Grain Rot of Rice. AB - A disease forecast model for bacterial grain rot (BGR) of rice, which is caused by Burkholderia glumae, was developed in this study. The model, which was named 'BGRcast', determined daily conduciveness of weather conditions to epidemic development of BGR and forecasted risk of BGR development. All data that were used to develop and validate the BGRcast model were collected from field observations on disease incidence at Naju, Korea during 1998-2004 and 2010. In this study, we have proposed the environmental conduciveness as a measure of conduciveness of weather conditions for population growth of B. glumae and panicle infection in the field. The BGRcast calculated daily environmental conduciveness, Ci , based on daily minimum temperature and daily average relative humidity. With regard to the developmental stages of rice plants, the epidemic development of BGR was divided into three phases, i.e., lag, inoculum build-up and infection phases. Daily average of Ci was calculated for the inoculum build up phase (Cinf ) and the infection phase (Cinc ). The Cinc and Cinf were considered environmental conduciveness for the periods of inoculum build-up in association with rice plants and panicle infection during the heading stage, respectively. The BGRcast model was able to forecast actual occurrence of BGR at the probability of 71.4% and its false alarm ratio was 47.6%. With the thresholds of Cinc = 0.3 and Cinf = 0.5, the model was able to provide advisories that could be used to make decisions on whether to spray bactericide at the pre- and post heading stage. PMID- 26672895 TI - Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review. AB - BACKGROUND: Ipilimumab improves survival in metastatic melanoma patients. This population frequently develops brain metastases, which have been associated with poor survival and are often treated with radiation. Therefore, outcomes following ipilimumab and radiation are of interest, especially given case reports and animal studies suggest combined treatment may generate abscopal responses outside the radiation field. FINDINGS: We reviewed sixteen consecutive melanoma patients who received 1 to 8 courses of radiation, with a sum total of 51, systematically evaluating abscopal responses by following the largest extra-cranial lesion. We also reviewed other series of patients treated with cranial radiation and ipilimumab. Our patients received between 1 and 8 courses of cranial radiation. Four patients received radiation concurrently with ipilimumab. Median survival was 14 months, and 17 months in patients initially treated with SRS. Interestingly, after radiotherapy, there was a 2.8-fold increased likelihood that the rate of extra-cranial index lesion response improved that didn't reach statistical significance (p = 0.07); this was more pronounced when ipilimumab was administered within three months of radiation (p < 0.01). CONCLUSION: Our experience and review of recently published series suggest ipilimumab and cranial radiation is well tolerated and can result in prolonged survival. Timing of ipilimumab administration in relation to radiation may impact outcomes. Additionally, our results demonstrate a trend for favorable systemic response following radiotherapy worthy of further evaluation in studies powered to detect potential synergies between radiation and immunotherapy. PMID- 26672892 TI - Genetics of ischaemic stroke in young adults. AB - BACKGROUND: Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. SCOPE OF REVIEW: Here we review the single-gene causes of ischemic stroke, bringing the reader from the candidate gene method toward the exciting new horizons of genetic technology. MAJOR CONCLUSIONS: The aetiological diagnosis of ischemic stroke in young adults is more complex than in the elderly. The identification of a genetic cause is important to provide appropriate counseling and to start a correct therapy, when available. The advent of GWAS technology, such as for other complex pathological conditions, has contributed enormously to the understanding of many of these genetic bases. For success large, well phenotyped case cohorts are required, and international collaborations are essential. GENERAL SIGNIFICANCE: This review focuses on the main causes of genetically-based ischemic stroke in young adults, often classified as indeterminate, investigating also the recent findings of the GWAS, in order to improve diagnostic and therapeutic management. PMID- 26672894 TI - Weight Status and Blood Pressure among Adolescent African American Males: The Jackson Heart KIDS Pilot Study. AB - BACKGROUND: Obesity had not been considered a significant factor contributing to high levels of hypertension among African American males until recently. Epidemiologic research on heart disease among males has primarily focused on adults; however, the significant rise in obesity and hypertension prevalence among African American boys indicates that studies examining the relationship between excess body weight and elevated blood pressure among this high-risk population are critically needed. The purpose of our study was to examine the degree to which weight status has implications for elevated blood pressure among young African American males. METHODS: The data for this cross-sectional study were drawn from adolescent males (N=105), aged 12-19 years and who participated in the Jackson Heart KIDS Pilot Study - an offspring cohort study examining cardiovascular disease risks among adolescent descendants of Jackson Heart Study participants. Blood pressure was the primary outcome of interest and weight status was a key independent variable. Other covariates were fruit and vegetable consumption, physical activity, sleep, and stress. RESULTS: Approximately 49% of adolescent males in the study were overweight or obese. Bivariate and multiple variable analyses suggest that obesity may be correlated with elevated diastolic blood pressure (DBP) levels among African American boys. Results from ordinary least squared regression analysis indicate that the DBP for boys carrying excess weight was 4.2 mm Hg (P<.01) higher than the corresponding DBP for their normal weight counterparts, after controlling for age, fruit and vegetable consumption, physical activity, and sleep. CONCLUSIONS: Additional studies are needed to specify the manner through which excess weight and weight gain can accelerate the development and progression of CVD-related diseases among African American males over the life course, thereby providing evidenced-based information for tailored interventions that can reduce risks for premature morbidity, disability, and mortality among this group. PMID- 26672896 TI - First principles design of a core bioenergetic transmembrane electron-transfer protein. AB - Here we describe the design, Escherichia coli expression and characterization of a simplified, adaptable and functionally transparent single chain 4-alpha-helix transmembrane protein frame that binds multiple heme and light activatable porphyrins. Such man-made cofactor-binding oxidoreductases, designed from first principles with minimal reference to natural protein sequences, are known as maquettes. This design is an adaptable frame aiming to uncover core engineering principles governing bioenergetic transmembrane electron-transfer function and recapitulate protein archetypes proposed to represent the origins of photosynthesis. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID- 26672897 TI - Risks of thromboembolism associated with hormonal contraceptives related to body mass index and aging in Japanese women. AB - OBJECTIVE: The aim of this study is to estimate the risk of thromboembolism related to body mass index (BMI) and aging among users of hormonal contraceptives in Japan. METHODS: A case-control study of the risk of obesity and a descriptive study of the risk of age were conducted. We used the Pharmaceuticals and Medical Devices Agency database, and extracted thromboembolic events of combined oral contraceptive (COC) products. Control data were from the National Health and Nutrition Survey in Japan. Denominator of descriptive study was from IMS Health, JPM. RESULTS: A total of 306 thromboembolic events and 6423 controls were analyzed. The odds ratios (95% confidence interval) of the obesity groups (BMI >= 25) were 2.32 (1.71-3.15) for venous thromboembolism (VTE), 1.16 (0.62-2.18) for arterial embolism and thrombosis (ATE), and 1.83 (1.38-2.43) for overall thromboembolic events compared with the standard group (BMI of 18.5-24.9) as a reference. The estimated incidence rates of VTE, ATE and overall thromboembolic events per 10,000 person-years in users of therapeutic remedies for dysmenorrhea (35 MUg ethinylestradiol combined with norethisterone, 20 MUg ethinylestradiol combined with drospirenone and dienogest) among women aged 10-59 years from 2009 to 2013 were 2.38 (2.08-2.74), 0.63 (0.48-0.82), and 3.17 (2.81-3.57), respectively. This tendency was not seen for dienogest. CONCLUSIONS: The risk of VTE in the obesity group among COC users was more than 2 times higher than in the standard group. The incidence rates of VTE in Japanese users of all remedies for dysmenorrhea except dienogest were as high as in people in Western countries. PMID- 26672898 TI - Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. AB - INTRODUCTION: Direct oral anticoagulant (DOAC) intra- and inter-individual variability was previously reported, but its magnitude is still considered negligible for patient management. OBJECTIVE: To evaluate inter- and intra individual variability in real-world atrial fibrillation patients on dabigatran, rivaroxaban or apixaban in four Italian anticoagulation clinics and to assess the correlation between DOAC plasma concentration and creatinine-clearance (CrCl). MATERIALS AND METHODS: A total of 330 consecutive patients were enrolled, of which 160 were on dabigatran (70 and 90 taking 150 mg or 110 mg twice-daily, respectively), 71 on rivaroxaban (37 and 34 taking 20mg or 15 mg once-daily) and 99 on apixaban (73 and 26 taking 5mg or 2.5mg twice-daily). Blood was taken at trough and peak within the first month (15-25 days) of treatment. Diluted thrombin-time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban was performed. RESULTS: Mean inter-individual variability expressed as overall CV values for all drugs was lower at peak (CV=46%) than at trough (CV=63%). Mean CV% intra-individual variability was 36.6% at trough and 34.0% at peak. Correlation with CrCl was poor for all drugs and only dabigatran at trough showed a significant correlation. CONCLUSION: This multicenter study confirms high DOAC inter-individual variability that cannot be explained by the rate of renal clearance to which the three DOAC were subjected since the correlation with CrCl was relatively poor. This poor correlation suggests caution in using CrCl as the sole laboratory parameter to indirectly evaluate residual circulating DOAC. PMID- 26672899 TI - Analysis of RNA metabolism in peripheral WBCs of TDP-43 KI mice identifies novel biomarkers of ALS. AB - Diagnostic biomarkers for amyotrophic lateral sclerosis (ALS) have yet to be identified. One of the causes of neuronal cell death in neurodegenerative diseases is abnormal RNA metabolism, although the mechanisms by which this occurs are unclear. Detection of abnormal RNA metabolism in white blood cells (WBCs) could lead to a new biomarker of ALS onset. TAR DNA-binding protein 43kDa (TDP 43) is an RNA-binding protein that regulates RNA metabolism. We previously developed a mouse model of ALS that exhibits adult-onset motor dysfunction; these mutant TDP-43 knock in (KI) mice heterozygously express mutant human TDP-43 (A382T or G348C). In the present study, we examined TDP-43 mRNA levels in WBCs of KI mice and found that A382T mutant mRNA is significantly higher than G348C. Our results suggest that each mutant TDP-43 induces distinct RNA metabolism, and that the expression of total TDP-43 alone in WBC is not suitable as an ALS biomarker. To identify additional candidates, we focused on survival and apoptosis-related factors and examined their mRNA metabolism in WBCs. mRNA levels of both Smn1 and Naip5 correlated with TDP-43 levels and also differed between A382T and G348C. Together, TDP-43 and these factors may enable detection of abnormalities in individual ALS pathologies. PMID- 26672900 TI - RETURN TO HITTING: AN INTERVAL HITTING PROGRESSION AND OVERVIEW OF HITTING MECHANICS FOLLOWING INJURY. AB - BACKGROUND AND PURPOSE: Participation in baseball is prevalent across all age groups. Baseball injuries are common and can impact a player's ability to participate. An injury to any region can influence the player's ability to swing the bat. As a part of the athlete's rehabilitation, a sports-specific program should be implemented re-introducing the hitting cycle that addresses proper biomechanics as well as providing a progressive atmosphere to return to hitting. Although there are several return to throwing progression programs in the literature, to the author's knowledge no published hitting progression programs exist. Thus, the purpose of this clinical commentary is to propose a progressive return to hitting program that emphasizes proper mechanics for ballplayers who have sustained an injury. DESCRIPTION OF TOPIC: This return to hitting program describes in detail the phases of the baseball hitting cycle. Proper biomechanical information is provided on each phase that can be used to assist the clinician in injury prevention. This article gives the healthcare professional guidance for assessment for appropriate readiness for return to sport using impairment measures, patient-report measures, and physical performance measures. The purpose of this hitting progression is to provide a safe, gradual increase in hitting intensity by moving from a fixed position to soft toss and finally to increasing pitch velocity. DISCUSSION: This interval hitting program guides the clinician from when the patient is ready to begin hitting through a full return to sport. Use of appropriate hitting mechanics must be ensured during rehabilitation to avoid compensation. Similar to the return to throwing programs that exist, this interval hitting progression program can provide a framework to quantify progression and reduce the chance of re-injury from occurring during the return to sport phase of rehab. LEVEL OF EVIDENCE: Level 5. PMID- 26672901 TI - Midwifery student exposure to workplace violence in clinical settings: An exploratory study. AB - Evidence indicates that nurses regularly experience bullying within the workplace which has the potential for health and social effects, as well as worker attrition. Literature suggests that nursing students are exposed to workplace violence during clinical placements including from health professionals and mentors, however little is known about midwifery students. This study sought to examine undergraduate midwifery students' experiences of workplace violence during clinical placements. A cross-sectional approach using a paper-based survey, the Paramedic Workplace Questionnaire, was used to solicit the information. Students were exposed to workplace violence with the main act being intimidation (30%), verbal abuse (17%), physical abuse (3%), and sexual harassment (3%). In more than three-quarters of the incidents the students had some level of apprehension or were frightened as a result of the violence. Students responded to the acts of violence with changes to emotions, self confidence, and a desire to "give up". This paper demonstrates ways in which midwifery students are vulnerable to potential workplace violence from various sources. Support mechanisms need to be developed to ensure this can be minimised. PMID- 26672902 TI - Repetition effects in human ERPs to faces. AB - In the present paper, we review research conducted over the past 25 years addressing the effects of repeating various kinds of information in faces (e.g., pictorial, spatial configural, identity, semantic) on different components in human event-related brain potentials (ERPs). This body of evidence suggests that several ERP components are systematically linked to different functional components of face identity processing. Specifically, we argue (1) that repetition of the category of faces (categorical adaptation) strongly affects the occipitotemporal N170 amplitude, which is systematically suppressed when a face is preceded by another face, irrespective of its identity, whereas (2) the prototypicality of a face's second order spatial configuration has a prominent effect on the subsequent occipitotemporal P200. Longer-latency repetition effects are related to the processing of individual facial identities. These include (3) an ERP correlate of the transient activation of individual representations of repeated faces in the form of an enhanced occipitotemporal N250r as seen in repetition priming experiments, and (4) a correlate of the acquisition of individual face identity representations during learning as seen in a topographically similar long-lasting N250 effect. Finally, (5) the repetition of semantic information in familiar person recognition elicits a central-parietal N400 ERP effect. We hope that this overview will encourage researchers to further exploit the potential of ERPs to provide a continuous time window to neuronal correlates of multiple processes in face perception under comparatively natural viewing conditions. PMID- 26672903 TI - Innovative application of classic and newer techniques for the characterization of haemocytes in the New Zealand black-footed abalone (Haliotis iris). AB - Haemocytes play an important role in innate immune responses within invertebrate organisms. However, identification and quantification of different types of haemocytes can be extremely challenging, and has led to numerous inconsistencies and misinterpretations within the literature. As a step to rectify this issue, we present a comprehensive and detailed approach to characterize haemocytes using a combination of classical (cytochemical and phagocytosis assays with optical microscopy) and novel (flow cytometry with Sysmex XN-1000 and Muse((r)) Cell analyser) techniques. The Sysmex XN-1000 is an innovative fluorescent flow cytometric analyser that can effectively detect, identify and count haemocytes, while the Muse((r)) Cell analyser provides accurate and rapid haemocyte cell counts and viability. To illustrate this approach, we present the first report on morphological and functional features of New Zealand black-footed abalone (Haliotis iris) haemocyte cells. Two types of haemocytes were identified in this study, including type I (monocyte-like) and type II (lymphocyte-like) cells. Granular cells, which have been reported in other molluscan species, were not detected in H. iris. Cell types were categorized based on shape, size, internal structures and function. The lymphocyte-like haemocytes were the most abundant hemocytes in the haemolymph samples, and they had large nuclei and basic cytoplasms. Monocyte-like cells generally were larger cells compared to lymphocyte-like cells, and had low nucleus-cytoplasm ratios. Monocyte-like cells showed higher phagocytic activity when encountering Zymosan A particles compared to lymphocyte-like cells. The present study provides a comprehensive and accurate new approach to identify and quantify haemocyte cells for future comparative studies on the immune system of abalone and other molluscan species. PMID- 26672904 TI - Dietary administration of a commercial mixed-species probiotic improves growth performance and modulates the intestinal immunity of tilapia, Oreochromis niloticus. AB - The growth performance, immunological status, intestinal morphology and microbiology of tilapia, Oreochromis niloticus, were investigated after dietary administration of the commercial probiotic AquaStar((r)) Growout. Tilapia (29.02 +/- 0.33 g) were split into five treatments; control (CON), 1.5 g kg(-1) probiotic (PRO-1.5), 3 g kg(-1) probiotic (PRO-3), pulsed probiotic feeding (PRO PULSE) or an initial probiotic feed followed by control feeding (PRO-INI). After six weeks of experimental feeding, fish fed PRO-3 displayed significantly higher final weight, weight gain and SGR compared to the CON or PRO-INI treatments. Supplementation of the probiotic at this dose induced an up-regulation of intestinal caspase-3, PCNA and HSP70 mRNA levels compared to the CON fed fish. Immuno-modulatory pathways were also affected; significantly higher expression of TLR2, pro-inflammatory genes TNFalpha and IL-1beta, and anti-inflammatory genes IL-10 and TGFbeta suggest that the probiotic may potentiate a higher state of mucosal tolerance and immuno-readiness. Histological appraisal revealed significantly higher numbers of intraepithelial leucocytes in the intestine of PRO-3 fed fish compared with treatments CON, PRO-PULSE and PRO-INI but not PRO 1.5. Additionally, fish receiving PRO-3 had a significantly higher abundance of goblet cells in their mid-intestine when compared with fish from all other treatments. Together, these data suggest that continuous provision of AquaStar((r)) Growout at 3 g kg(-1) can improve tilapia growth and elevate the intestinal immunological status of the host. PMID- 26672906 TI - Rheumatoid cachexia: the undiagnosed, untreated key to restoring physical function in rheumatoid arthritis patients? PMID- 26672905 TI - Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt. AB - OBJECTIVES: Assess the effectiveness and safety of biologic therapy as well as predictors of response at 1 year of therapy, retention rate in biologic treatment and predictors of drug discontinuation in JIA patients in the Portuguese register of rheumatic diseases. METHODS: We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent. RESULTS: A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016). CONCLUSION: Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years. PMID- 26672907 TI - The majority of patients do not store their biologic disease-modifying antirheumatic drugs within the recommended temperature range. AB - OBJECTIVE: To monitor whether biologic DMARD (bDMARD) home storage temperatures comply with the manufacturers' Summary of Product Characteristics (SmPC) recommendations. METHODS: This observational study included consenting adult patients from eight Dutch pharmacies who received their bDMARDs with a validated temperature logger. Patients were instructed to store their packages according to standard label instructions and to return the temperature logger(s) after use. Primary outcome was defined as the proportion of patients that stored their bDMARDs within the SmPC recommended temperature range. In addition, the proportion of patients storing bDMARDs below 0 degrees C or above 25 degrees C for longer than two consecutive hours was estimated. RESULTS: A total of 255 (87.0%) patients (mean age 53.2 (s.d.; 13.1) years, 51.4% female) returned their temperature logger(s) to the pharmacy. Of these, 17 patients (6.7%) stored their bDMARD within the recommended temperature range. The proportion of the patients that stored their bDMARD for more than 2 h consecutive time below 0 degrees C or above 25 degrees C was respectively 24.3% (median duration: 3.7 h (IQR 2.2 h; range 2.0-1,097.1 h) and 2.0% (median duration: 11.8 h (IQR 44.3 h; range 2.0 381.9 h). CONCLUSION: The majority of patients do not store their bDMARDs within the SmPC-recommended temperature range. PMID- 26672908 TI - Abatacept (CTLA-4Ig) treatment reduces T cell apoptosis and regulatory T cell suppression in patients with rheumatoid arthritis. AB - OBJECTIVE: Abatacept (CTLA-4Ig) blocks CD28-mediated T cell activation by binding to the costimulatory B7 ligands CD80/CD86 on antigen presenting cells. Costimulatory molecules, however, can also be expressed on T cells upon activation. Therefore, the aim of our study was to investigate direct effects of CTLA-4Ig on distinct T cell subsets in RA patients. METHODS: Phenotypic and functional analyses of CD4(+) T cells, including CD4(+) FoxP3(+) CD25(+) regulatory T cells (Treg), from RA patients were performed before and during CTLA 4Ig therapy. In addition T cells from healthy volunteers were analysed on in vitro culture with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies. Apoptotic DNA fragmentation in CD4(+) and CD4(+) FoxP3(+) T cells was measured by TUNEL staining. RESULTS: We observed an increase in T cells, including Treg cells, after initiation of CTLA-4Ig therapy, which was linked to a downregulation of activation-associated marker molecules and CD95 on CD4(+) T cells and Treg cells. CTLA-4Ig decreased CD95-mediated cell death in vitro in a dose-dependent manner. Functional analysis of isolated Treg cells from RA patients further revealed a diminished suppression of responder T cell proliferation. This was found to be due to CTLA-4Ig-mediated blocking of CD80 and CD86 on responder T cells that led to a diminished susceptibility for Treg cell suppression. CONCLUSION: CTLA-4Ig therapy in RA patients exerts effects beyond the suppression of T cell activation, which has to be taken into account as an additional mechanism of CTLA 4Ig treatment. PMID- 26672909 TI - Assessment of arterial stiffness from pedal artery Korotkoff sound recordings: feasibility and potential utility. AB - Brachial artery (BA) Korotkoff sound (KS) timing reflects arterial stiffness. We recorded pedal artery (PA) KS in 68 healthy subjects using an electronic stethoscope and electrocardiography. Intervals between QRS complex of the electrocardiogram and KS waveform peaks (termed the QKD interval) were measured for 60 seconds, averaged, and QKD velocity (v) calculated. Carotid-BA and carotid PA pulse wave velocities (PWVs) were measured by applanation tonometry. Analyzable KS recordings were obtained from BA and PA in 100% and 92% subjects. PA QKDv decreased less than BA QKDv with progressive cuff inflation. At diastolic blood pressure + 20 mm Hg (maximal yield), BA QKDv was independently associated with weight and pulse pressure, whereas PA QKDv was related to weight and age. PA QKDv correlated with its corresponding PWV stronger than BA QKDv. In conclusion, PA KS is optimally recorded at diastolic blood pressure + 20 mm Hg; PA QKDv is correlated with age and better correlates with PWV than does BA QKDv. This technique may provide a simple arterial stiffness measure. PMID- 26672910 TI - Is inflammatory bowel disease in dogs and cats associated with a Th1 or Th2 polarization? AB - Mucosal immunity involves complex interactions to generate either immune tolerance or active immune responses. An imbalance of pro- and anti-inflammatory cytokines and chemokines that drive the recruitment of immune cells to the intestinal mucosa are a key characteristic of inflammatory bowel disease in humans, where distinctive helper-T-lymphocyte profiles help to discriminate between Crohn's disease and ulcerative colitis. This review evaluates the current veterinary literature to determine whether a Th1/Th2 (and possibly also Th17) polarization also exists in canine and feline inflammatory bowel disease. PMID- 26672911 TI - Development and characterization of monoclonal antibodies against goose CD3E extracellular domain and their application in detection of CD3(+) T lymphocytes. AB - CD3 is one of the most important cell surface markers of T lymphocytes, and has an important function in signal transmission during antigen recognition. In this study, monoclonal antibodies against goose CD3E extracellular domain were developed and characterized for the first time. The purified recombinant goose CD3E extracellular domain protein and pcDNA3.1-GoCD3Eex were used as immunogens to develop mAbs. Furthermore, recombinant protein was used to screen for mAbs. The characteristics of mAbs were identified through IFA, I-ELISA, Western blot, FCM, and LSCM analyzes. Results showed that mAbs 3C11 and 5A3 may be good candidates for use in detecting goose T lymphocytes and in immunoassaying and exploring the function of the CD3E molecule. PMID- 26672913 TI - Dose-dependent pathogenicity of a pseudorabies virus variant in pigs inoculated via intranasal route. AB - Pseudorabies (PR) or Aujeszky's disease (AD), caused by pseudorabies virus (PRV), is an economically important viral disease in many countries. The modified live vaccine Bartha-K61 strain has played an important role in the control of PR in many countries including China. Since late 2011, however, increasing PR outbreaks caused by an emerging PRV variant have been reported in Bartha-K61-vaccinated swine population on many farms in China. Previously, we showed that the PRV variant TJ strain exhibited enhanced pathogenicity in pigs inoculated via intramuscular route. To develop an animal infection model for accurate evaluation of novel vaccines against the emergent PRV variant, we evaluated the pathogenicity of the PRV TJ strain of different doses in pigs infected via intranasal route. Groups (n=5) of 7-week-old healthy pigs were inoculated intranasally with 10(3), 10(4), 10(5), or 10(6) TCID50 (median tissue culture infective dose) PRV TJ strain. Clinical signs, rectal temperature, virus shedding, pathological changes, and seroconversion were monitored. The results showed that the PRV TJ strain induced varied morbidity and mortality (0/5 to 5/5), clinical signs, and tissue lesions, increasingly correlated with the infection doses, and the median lethal dose (LD50) of the virus was determined to be 10(4.5) TCID50. Together, this study demonstrates the dose-dependent pathogenicity of the PRV variant via the intranasal route of infection, which provides an ideal animal infection model for evaluation of novel vaccines against the emerging PRV variant. PMID- 26672912 TI - Immunophenotyping of immune cell populations in the raccoon (Procyon lotor). AB - The raccoon (Procyon lotor) is a highly adaptable carnivore that has rapidly conquered Europe over the last decades and represents a potential candidate as pathogen reservoir, bearing the risk for transmission of infectious agents, as zoonosis or spill-over, to other wild life and domestic animals and man. Comprehensive investigations of infectious diseases in raccoons require a detailed knowledge of the participating immune cell populations. To close this gap of knowledge, various antibodies were tested for cross-reactivity with leukocytes in lymphoid organs and peripheral blood of raccoons using immunohistochemistry and flow cytometry, respectively. Eight out of 16 antibodies, directed against CD3, CD79alpha, Pax-5, IgG, CD44, MHC class II, myeloid/histiocyte antigen (MAC387), and Iba-1 exhibited a specific immunoreaction with cells in distinct anatomical compartments in formalin-fixed paraffin-embedded lymphoid tissues. Flow cytometric analysis revealed that 7 out of 18 antibodies directed against CD11c, CD14, CD21, CD44, CD79alpha, MHC class I and II cross-reacted with peripheral blood-derived raccoon leukocytes. Summarized, the usefulness of several cross-reacting antibodies was determined for the characterization of raccoon immune cells in immunohistochemistry and flow cytometry, offering the opportunity to study the raccoon immune system under normal and diseased conditions. PMID- 26672914 TI - First comparison of adjuvant for trivalent inactivated Haemophilus parasuis serovars 4, 5 and 12 vaccines against Glasser's disease. AB - Haemophilus parasuis has had a huge impact in the swine industry throughout the world. Inactivated bacterium for H. parasuis is a traditional vaccine that can elicit efficient protection against homologous challenges. The objective of this study was to screen for the adjuvant-enhanced immune effect of trivalent inactivated H. parasuis serovars 4, 5 and 12 (prevalent serovars in China) vaccines against Glasser's disease. The adjuvants of mineral oil, aluminum hydroxide, Montanide GEL 01 PR, Montanide IMS 1313N VG and Montanide ISA 760 VG were used to make emulsified inactivated H. parasuis serovars 4, 5 and 12, respectively. Safety, antibody titer and protective efficacy of these vaccines were examined separately in piglets, and the feasibility of microagglutination test for detecting antibody titer of H. parasuis was confirmed for the first time. Due to easy of injection, high safety, rapidly immune responses, high concentrations of antibody, and 100% of protective efficacy for piglets, Montanide GEL 01 PR adjuvant can provide more homologous serovar protection than other domestically developed inactivated vaccines and should be used as a candidate adjuvant. PMID- 26672915 TI - Morcellation of undiagnosed uterine sarcoma: A critical review. AB - In the recent decades, laparoscopy has replaced open abdominal procedures in the setting of gynecologic surgery. Extraction of large specimens (e.g., large uteri or myomas) following operative laparoscopy is technically challenging. Technological attempts allow the removal of large and solid pelvic masses via small abdominal incisions (using instruments called morcellators), thus reducing unnecessary laparotomies and improving short-term patients' outcomes. However, morcellation of undiagnosed uterine malignancies may lead to worse survival outcomes. Therefore, the Food and Drug Administration (FDA) warns about the use of power morcellators, thus causing ongoing concerns on the applicability of minimally invasive approaches for myomectomy and the removal of large uteri. In the present review, we sought to assess pro and cons regarding minimally invasive morcellation. This review will discuss the effects of morcellation of undiagnosed uterine malignancies, focusing on possible techniques for preoperative detection of uterine sarcoma and for avoiding intra-abdominal dissemination of potentially malignant tissues. Further efforts are necessary in order to identify tools to make a more accurate and reliable preoperative diagnosis of uterine masses. However, on the light of the current evidence, intra-abdominal morcellation should be banned from clinical practice. PMID- 26672916 TI - Pregnancy and sickle cell disease: A review of the current literature. AB - Sickle cell disease (SCD) is the most common hereditary disease worldwide, presenting with anemia and intermittent severe pain. Pregnancy in a patient with SCD is associated with high levels of maternal and fetal morbidity and mortality; the maternal and fetal death rates during pregnancy can attain 11.4% and 20%, respectively. Patient care has improved over time. However, certain management issues remain unresolved; these include the optimum policy in terms of prophylactic blood transfusion, and the use of antiplatelet drugs. Such issues are attributable to the heterogeneous nature of clinical SCD features, and the limitations of uncontrolled and prospective trials. In this review, we seek to facilitate a better understanding of relevant issues via creation of a comparative data profile extracted from current studies. This report may also encourage the drafting of standard operating procedure for management of pregnancy in SCD patients. PMID- 26672917 TI - Computational based functional analysis of Bacillus phytases. AB - Phytase is an enzyme which catalyzes the total hydrolysis of phytate to less phosphorylated myo-inositol derivatives and inorganic phosphate and digests the undigestable phytate part present in seeds and grains and therefore provides digestible phosphorus, calcium and other mineral nutrients. Phytases are frequently added to the feed of monogastric animals so that bioavailability of phytic acid-bound phosphate increases, ultimately enhancing the nutritional value of diets. The Bacillus phytase is very suitable to be used in animal feed because of its optimum pH with excellent thermal stability. Present study is aimed to perform an in silico comparative characterization and functional analysis of phytases from Bacillus amyloliquefaciens to explore physico-chemical properties using various bio-computational tools. All proteins are acidic and thermostable and can be used as suitable candidates in the feed industry. PMID- 26672918 TI - Soyasaponin Ab inhibits lipopolysaccharide-induced acute lung injury in mice. AB - Soyasaponin Ab (SA) has been reported to have anti-inflammatory effect. However, the effects of SA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) have not been reported. The aim of this study was to investigate the anti inflammatory effects of SA on LPS-induced ALI and clarify the possible mechanism. The mice were stimulated with LPS to induce ALI. SA was given 1h after LPS treatment. 12h later, lung tissues were collected to assess pathological changes and edema. Bronchoalveolar lavage fluid (BALF) was collected to assess inflammatory cytokines and nitric oxide (NO) production. In vitro, mice alveolar macrophages were used to investigate the anti-inflammatory mechanism of SA. Our results showed that SA attenuated LPS-induced lung pathological changes, edema, the expression of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissues, as well as TNF-alpha, IL-6, IL-1beta, and NO production in mice. Meanwhile, SA up-regulated the activities of superoxide dismutase (SOD) and catalase decreased by LPS in mice. SA also inhibited LPS-induced TNF-alpha, IL-6 and IL-1beta production as well as NF-kappaB activation in alveolar macrophages. Furthermore, SA could activate Liver X Receptor Alpha (LXRalpha) and knockdown of LXRalpha by RNAi abrogated the anti-inflammatory effects of SA. In conclusion, the current study demonstrated that SA exhibited protective effects against LPS-induced acute lung injury and the possible mechanism was involved in activating LXRalpha, thereby inhibiting LPS-induced inflammatory response. PMID- 26672919 TI - Safety of the CO-Rebreathing Method in Patients with Coronary Artery Disease. AB - PURPOSE: To address and study the safety concerns with the improved carbon monoxide (CO) rebreathing method for measuring total blood volume in patients with coronary artery disease to implement the use of the methodology in this patient group. METHODS: Eighteen patients with stable coronary artery disease (age 62 +/- 7 yr, 24 +/- 5 months since diagnosis) were investigated using the improved CO-rebreathing test. Before, during, and up to 2 h after the test, ECG, blood pressure, arterial oxygen saturation, carbon monoxide bound to hemoglobin (HbCO%), and cardiac function were measured. At 24 h, HbCO% and troponin-T were measured. DESIGN: Cross-over. RESULTS: Six minutes after the CO-rebreathing test, HbCO increased from 1.5% +/- 0.4% to 6.0% +/- 0.6%, with a subsequent decrease to 4.5% +/- 0.4% and 1.4% +/- 0.4% at 2 h and 24 h after the test, respectively. Resting heart rate, stroke volume, cardiac output, and ejection fraction were 64 +/- 11 bpm, 93.9 +/- 16.5 mL per beat, 5.84 +/- 0.99 L, and 48.5% +/- 5.7% and remained unchanged during and 10 min after the rebreathing. All patients were in sinus rhythm during the 2-h observation period, without ST- or T-wave changes, with low numbers of premature beats and normal rate variability. Systolic and diastolic blood pressure gradually decreased during the observation period. Troponin-T was below the 99th percentile for all the participants 24 h after the test. CONCLUSION: Cardiovascular function and safety indices remained unchanged after exposure to approximately 6% HbCO, indicating that the method is safe to perform in patients with stable coronary artery disease. PMID- 26672920 TI - Cycling Exercise Training Alleviates Hypoxia-Impaired Erythrocyte Rheology. AB - PURPOSE: Physical exercise or hypoxic exposure influences hemorheology and acid base homeostasis. Band 3 protein in erythrocytes modulates cells' rheological properties and anion transport ability. This study investigated how cycling aerobic interval training (AIT) and moderate continuous training (MCT) affect the rheological function and band 3 activity of erythrocytes under hypoxic exercise (HE) stress. METHODS: Forty-five healthy sedentary men were randomized to engage in either AIT (3-min intervals at 40% and 80% of VO2max, n = 15) or MCT (sustained 60% of VO2max, n = 15) on a bicycle ergometer for 30 min . d(-1) (5 d . wk(-1) for 5 wk) or to a control group that did not perform any exercise (n = 15). Erythrocyte rheological responses to HE (100 W under 12% O2 for 30 min) were determined before and after various regimens. RESULTS: Acute HE increased the aggregation and osmotic fragility of erythrocytes, decreased the deformability of erythrocytes, and depressed erythrocyte band 3 activity, as indicated by lowered anion transport ability. Following 5 wk of intervention, the AIT group exhibited maximal work rate and VO2max higher than those in the MCT and control groups. Moreover, cycling AIT and MCT diminished the extent of erythrocytes' enhanced aggregation and osmotic fragility and reduced their deformability and band 3 activity caused by HE. Additionally, erythrocyte band 3 activity was directly related to erythrocyte deformability and inversely related to erythrocyte aggregation and osmotic fragility. CONCLUSIONS: Cycling AIT is superior to cycling MCT in enhancing aerobic capacity. Moreover, either cycling AIT or MCT effectively alleviates HE-evoked impairments of erythrocyte rheological characteristics and band 3 function. PMID- 26672921 TI - Excellence in Critical Care Units. PMID- 26672922 TI - Equity of Access to Critical Care Among Elderly Patients in Scotland: A National Cohort Study. AB - OBJECTIVE: To compare elderly (>= 80 yr), older (65-79 yr), and younger (< 65 yr) ICU admissions in Scotland in relation to trends in admission rates, regional variation in admissions, ICU treatment intensity, and ICU and 1-year mortality. DESIGN: National 5-year cohort study of ICU first admissions (January 1, 2005, to December 31, 2009). SETTING: All admissions to ICUs and combined units (level 2/3 care) in Scotland captured by the Scottish Intensive Care Society Audit Group database, linked with hospital discharge data and death records. PATIENTS: A total of 40,142 patients: 3,865 were 80 years old or older (9.6%), 13,904 (34.6%) were 65-79 years old; and 22,373 were younger than 65 years (55.7%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2005 and 2009, elderly admission rates decreased from 36.6/10,000 (95% CI, 34.0-39.2) in 2005 to 28.7/10,000 (95% CI, 26.5-30.9) in 2009 (p < 0.001; relative decrease, 22.0%); older admission rates also decreased, but less steeply (31.1 [95% CI, 29.9-32.2] to 26.1 [95% CI, 25.1-27.1] per 10,000 population; p < 0.001; relative decrease, 16.1%). Rates were static for younger patients. Restricted to mechanically ventilated elderly patients, rates ranged from 13.9 to 30.1/10,000 between healthboard administrative regions (p < 0.001). Emergency surgical diagnoses were more prevalent for elderly patients (elderly, 39.8%; older, 25.1%; younger, 20.3%; p < 0.001). Subgroup analyses limited to pneumonia admissions (elderly, n = 242; older, n = 1,226; younger, n = 1,836) indicated similar acute physiology scores, but fewer preexisting comorbidities among elderly patients (p = 0.007), who received a shorter duration of organ support and ICU stay. Mortality rates were higher in elderly patients at ICU discharge (elderly, 26.5%; older, 25.0%; younger, 17.0%; p < 0.001; confounder adjusted odds ratio elderly vs younger, 2.33 [95% CI, 2.11-2.58]; p < 0.001). Differences persisted at 1 year (elderly, 52.2%; older, 43.8%; younger, 27.6%; adjusted odds ratio elderly vs younger, 3.72 [95% CI, 3.42-4.06]; p < 0.001). CONCLUSIONS: In Scotland, elderly and older ICU admission rates are decreasing, with regional geographic variation. Although limited by an absence of a measure of frailty, patient characteristics and treatment intensity suggest selection of less comorbid elderly patients, indicating possible rationing based on chronologic age. PMID- 26672924 TI - Nurse Research Experiences and Attitudes Toward the Conduct of Intensive Care Research: A Questionnaire Study. AB - OBJECTIVE: To characterize ICU nurses' research experience, work environments, and attitudes toward clinical research in critically ill adults and children. DESIGN: Cross-sectional survey. SETTING: Eight (seven adult and one pediatric) academic ICUs affiliated with the Canadian Critical Care Trials Group. PARTICIPANTS: Four hundred eighty-two ICU nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Response rate was 56%. Most participants had over 6 years of ICU experience (61%) and held a baccalaureate nursing degree (57%). Most participants (63%) had provided care for patients receiving research study procedures more than five times in the past 12 months and agreed that research leads to improved care for the critically ill (78%) and eligible patients should be approached for research participation (78%). Few perceived practicalities of nursing care are considered in study design (20%); 41% agreed that research studies increases nursing workload. Few participants reported receiving adequate information about study progress (24%) or findings (26%). Principal factor analysis identified three factors each in the environmental and attitudinal domains. Linear regression models demonstrated that positive relationships between researchers and clinicians were associated with favorable perceptions of research impact on nursing care (p < 0.001), ICU research acceptability (p < 0.001), and nursing engagement in research (p < 0.05). Nurses with more formal education reported more favorable attitudes toward nursing engagement in research (p < 0.01) and research acceptability (p < 0.01). Lack of experience in study protocol development and/or data analysis was associated with less favorable attitudes about nursing engagement in research (p < 0.01) and impact of research on nursing care (p < 0.01). CONCLUSION: In these research-intensive ICUs, nurses frequently care for research participants and believe ICU research is important. Inclusion of nurses in study protocol development, improved communication of study progress and findings, and investigation of research-related nursing workload are warranted. Such interventions will support intervention fidelity and data reliability during study conduct and translation of evidence into practice on study completion. PMID- 26672923 TI - Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial. AB - OBJECTIVE: The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. DESIGN: A prospective, multicenter, pilot, randomized controlled trial. SETTING: A network of 20 multidisciplinary ICUs. PATIENTS: Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. INTERVENTIONS: At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2>=0.5, positive end-expiratory pressure >=10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. MEASUREMENTS AND MAIN RESULTS: From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. CONCLUSIONS: In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome. PMID- 26672925 TI - Association Between High Arterial Oxygen Tension and Long-Term Survival After Spontaneous Intracerebral Hemorrhage. AB - OBJECTIVE: To determine the relation between high arterial oxygen tension levels (PaO2) and long-term mortality in patients with spontaneous intracerebral hemorrhage treated in the ICU. DESIGN: National observational multicenter cohort study. SETTING: Twenty-one ICUs in Finland. PATIENTS: A total of 3,033 adult patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into high (> 150 mm Hg), intermediate (97.5-150 mm Hg), and low (< 97.5 mm Hg) PaO2 groups based on the lowest measured PaO2/FIO2 ratio during the first 24 hours after ICU admission: 63% (n = 1,923) were in the low group, 29% (n = 892) were in the intermediate group, and 7% (n = 218) were in the high group; 80% were mechanically ventilated. The primary outcome was 6-month mortality, which occurred in 49% of patients and was significantly more frequent in the high PaO2 group than in the intermediate and low PaO2 groups (61% vs 52% and 46%, respectively, p < 0.001). In univariate analysis, patients in the high PaO2 group had a significantly increased risk of 6-month mortality compared with the low PaO2 group (odds ratio, 1.82; 95% CIs, 1.36-2.42; p < 0.001), but this statistically significant relation was lost after adjusting for markers of severity of illness in a logistic mixed-effects regression model (odds ratio, 1.10; 95% CI, 0.76-1.60; p = 0.598). CONCLUSIONS: No significant relation between PaO2 levels and long-term mortality was found. The clinical role of hyperoxemia in patients with intracerebral hemorrhage treated in the ICU remains controversial and warrants further studies. PMID- 26672926 TI - Precision Diagnosis Is a Team Sport. PMID- 26672927 TI - The Elderly Patient and the ICU: Where Are We Going, Where Should We Go? PMID- 26672928 TI - Ventilator-Associated Events in Neonates and Children: A Single Definition for a Heterogeneous Population. PMID- 26672929 TI - Selepressin in Septic Shock: A Step Toward Decatecholaminization? PMID- 26672930 TI - Should We Embrace the "Open Lung" Approach? PMID- 26672931 TI - Saving Patients' Lives Through Activating a Rapid Response System: Willing Is Not Enough, We Must Do. PMID- 26672932 TI - Fentanyl Pharmacokinetics in Critically Ill Patients: A Demonstration of Mixed Effects. PMID- 26672933 TI - Creatinine Tells a Longer Story Than Just "How Are My Kidneys?". PMID- 26672934 TI - Lung Protective Ventilator Strategies: Beyond Scaling Tidal Volumes to Ideal Lung Size. PMID- 26672935 TI - Nonintubated Patients With Acute Respiratory Distress Syndrome: A Watchful Evaluation. PMID- 26672936 TI - Shining a Light on the Problem of Circadian Phase Disruption in the Critically Ill. PMID- 26672937 TI - IV Immunoglobulin: A Useful Tool for the Severe Pneumonia Toolbox? PMID- 26672939 TI - Designing Better, Not Just Bigger, Multicenter Critical Care Trials. PMID- 26672940 TI - The authors reply. PMID- 26672941 TI - Impact of Drug Resistance on Virulence and Fitness of Bacterial Pathogens. PMID- 26672943 TI - Is Dead Space a New Marker for Gravity on Pediatric Acute Hypoxemic Respiratory Failure? PMID- 26672942 TI - The authors reply. PMID- 26672944 TI - The authors reply. PMID- 26672945 TI - Hyperchloremia Versus Nonhyperchloremia or Hyperchloremia Versus Normochloremia? PMID- 26672947 TI - Association of Postoperative Hypoalbuminemia With Acute Kidney Injury Following Liver Transplantation. PMID- 26672946 TI - The authors reply. PMID- 26672948 TI - The authors reply. PMID- 26672949 TI - More Than Meets the Eye: Supervision and Teaching Decisions Need to be Noticed Too. PMID- 26672950 TI - Concomitant Osteochondral Autograft Transplantation and Fixation of Osteochondral Fragment for Treatment of a Massive Osteochondritis Dissecans: A Report of 8-Year Follow-up Results. AB - Numerous procedures exist to treat osteochondritis dissecans (OCD); however, it remains a topic of debate which procedure is most ideal. When restoring a massive osteochondral defect, the use of only one procedure may not always allow complete filling of the defect. This case report presents a massive OCD with displaced osteochondral fragment and loose body in the knee joint that occupied almost all of the weight bearing area of the medial femoral condyle and was treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. To our knowledge, this is a rare report on OCD treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. At 8 years after surgery, the clinical outcome was excellent, and radiographs revealed congruence of the medial femoral condyle. The patient returned to sports activities. In massive and complex OCD lesions, individual techniques have limitations. Two or more techniques are needed to increase the rate of success. PMID- 26672951 TI - Benefits of a transfer clinic in adolescent and young adult kidney transplant patients. AB - BACKGROUND: Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. OBJECTIVE: The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. METHODS: We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. RESULTS: The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer was smaller in the group that attended the transition clinic (-0.9 +/- 13.2 ml/min/1.73 m(2)) compared to those who did not (-12.29 +/- 14.9 ml/min/1.73 m(2)), p = 0.045. CONCLUSIONS: Attendance at a single kidney transplant transfer clinic was associated with improved adherence and renal function in the year following transfer to adult care. If these changes are sustained, they may improve long-term graft outcomes for adolescent kidney transplant recipients. PMID- 26672952 TI - Hormetic Responses of Lonicera Japonica Thunb. To Cadmium Stress. AB - The hormetic responses of Lonicera japonica Thunb. to cadmium (Cd) stress were investigated in a hydroponic experiment. The present results showed that root length and total biomass dry weight increased in comparison with the control at low concentrations Cd. The height of the plant exposed to 2.5 and 5 mg L(-1) Cd increased significantly by 11.9% and 12.8% relative to the control, and with the increase of Cd concentrations in the medium, plant height began to decrease. The responses of photosynthetic pigments contents and relative water content to Cd stress had a similar trend, which all showed significantly an inverted U-shaped dose-response curve and confirmed that the stimulatory effect of low concentrations Cd occurred in the plant. Furthermore, L. japonica, as a new Cd hyperaccumulator, could be considered as a new plant model to study the underlying mechanisms of the hormesis. PMID- 26672954 TI - Tuning surface grafting density of CeO2 nanocrystals with near- and supercritical solvent characteristics. AB - In this work, the solvent effect on the synthesis of CeO2 nanocrystals synthesized in near- and supercritical alcohols is discussed. The materials prepared displayed a unique morphology of small nanocrystals (<10 nm) aggregated into larger nanospheres (~100-200 nm). In such syntheses, alcohol molecules directly interact with the nanocrystal surface through alkoxide and carboxylate bondings. The grafting density was quantified from the weight loss measured using thermogravimetric analysis. A direct correlation between the grafting density and the alcohol chain length can be established. It was demonstrated that the shorter the alcohol chain length (i.e. methanol), the higher the surface coverage is. This trend is independent of the synthesis mode (batch or continuous). Additionally, an influence of the grafting density on the resulting nanocrystal size was established. It is suggested that the surface coverage has a high influence on the early stages of the nucleation and growth. Indeed, when high surface coverages are reached, all surface active sites are blocked, limiting the growth step and therefore leading to smaller particles. This effect was noticed with the materials prepared in the continuous mode where shorter reaction time was performed. PMID- 26672955 TI - YKL-40 and genetic status of CHI3L1 in a large group of asthmatics. AB - BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40, and SNP (-131 C/G, rs4950928). METHODS: In this study, 1,137 patients with asthma, 415 with rhinitis only, and 275 non-asthmatic controls were included. Assessment included a clinical interview concerning the diagnosis of asthma, severity of asthma, and asthma treatment as well as clinical tests to assess asthma and rhinitis. Serum YKL-40 was measured, and genotyping for the SNP (-131 C/G) was conducted. RESULTS: No significant difference in the serum concentration of YKL-40 was found between patients with asthma, patients with rhinitis, and non-asthmatic controls; however, YKL-40 was increased in patients with severe asthma. No association was found between the SNP (-131 C/G rs4950982) and the risk of having asthma (odds ratio = 0.90, p=0.4). Higher levels of serum YKL-40 were found in all subjects when comparing CC genotype to CG and GG genotypes (45 ug/L vs. 32 ug/L and 19 ug/L, p<0.0001). CONCLUSION: There was no association between polymorphisms of SNP (-131 C/G) and asthma. The highest serum YKL-40 concentrations were seen in severe asthmatics. Individuals with less severe asthma showed a smaller difference against controls, limiting its clinical usefulness. More research is needed to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1. PMID- 26672956 TI - Systemic sarcoidosis mimicking malignant metastatic disease. AB - We present a case of systemic sarcoidosis involving the liver, pancreas, lungs, mediastinal and intraabdominal lymph nodes and bones. Multiple organ system manifestations mimicked malignant metastatic disease. The diagnosis was established with clinical, radiological, and pathological findings after neoplasm was ruled out by pathological tests. The patient showed rapid symptom remission with systemic steroid treatment. PMID- 26672957 TI - The contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases. AB - The prevalence of asthma and other atopic diseases has increased markedly during the past decades and the reasons for this are not fully understood. Asthma is still increasing in many parts of the world, notably in developing countries, and this emphasizes the importance of continuing research aimed at studying the aetiological factors of the disease and the causes of its increase in prevalence. Twin studies enable investigations into the genetic and environmental causes of individual variation in multifactorial diseases such as asthma. Thorough insight into these causes is important as this will ultimately guide the development of preventive strategies and targeted therapies. This review explores the contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases. PMID- 26672958 TI - Nurses' and patients' communication in smoking cessation at nurse-led COPD clinics in primary health care. AB - BACKGROUND: Smokers with chronic obstructive pulmonary disease (COPD) have high nicotine dependence making it difficult to quit smoking. Motivational interviewing (MI) is a method that is used in stimulating motivation and behavioral changes. OBJECTIVE: To describe smoking cessation communication between patients and registered nurses trained in MI in COPD nurse-led clinics in Swedish primary health care. METHODS: A prospective observational study with structured quantitative content analyses of the communication between six nurses with basic education in MI and 13 patients in non-smoking consultations. RESULTS: Only to a small extent did nurses' evoke patients' reasons for change, stimulate collaboration, and support patients' autonomy. Nurses provided information, asked closed questions, and made simple reflections. Patients' communication was mainly neutral and focusing on reasons for and against smoking. It was uncommon for patients to be committed and take steps toward smoking cessation. CONCLUSION: The nurses did not adhere to the principles of MI in smoking cessation, and the patients focused to a limited extent on how to quit smoking. PRACTICE IMPLICATIONS: To make patients more active, the nurses need more education and continuous training in motivational communication. PMID- 26672960 TI - 47th Nordic Lung Congress - Oslo 2015. PMID- 26672959 TI - Exercise and asthma: an overview. AB - The terms 'exercise-induced asthma' (EIA) and 'exercise-induced bronchoconstriction' (EIB) are often used interchangeably to describe symptoms of asthma such as cough, wheeze, or dyspnoea provoked by vigorous physical activity. In this review, we refer to EIB as the bronchoconstrictive response and to EIA when bronchoconstriction is associated with asthma symptoms. EIB is a common occurrence for most of the asthmatic patients, but it also affects more than 10% of otherwise healthy individuals as shown by epidemiological studies. EIA and EIB have a high prevalence also in elite athletes, especially within endurance type of sports, and an athlete's asthma phenotype has been described. However, the occurrence in elite athletes shows that EIA/EIB, if correctly managed, may not impair physical activity and top sports performance. The pathogenic mechanisms of EIA/EIB classically involve both osmolar and vascular changes in the airways in addition to cooling of the airways with parasympathetic stimulation. Airways inflammation plays a fundamental role in EIA/EIB. Diagnosis and pharmacological management must be carefully performed, with particular consideration of current anti-doping regulations, when caring for athletes. Based on the demonstration that the inhaled asthma drugs do not improve performance in healthy athletes, the doping regulations are presently much less strict than previously. Some sports are at a higher asthma risk than others, probably due to a high environmental exposure while performing the sport, with swimming and chlorine exposure during swimming as one example. It is considered very important for the asthmatic child and adolescent to master EIA/EIB to be able to participate in physical activity on an equal level with their peers, and a precise early diagnosis with optimal treatment follow-up is vital in this aspect. In addition, surprising recent preliminary evidences offer new perspectives for moderate exercise as a potential therapeutic tool for asthmatics. PMID- 26672961 TI - Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection. AB - BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs. PMID- 26672963 TI - Airway resistance and reactance are affected in systemic sclerosis. AB - BACKGROUND: Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc. METHODS: Seventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls. RESULTS: Patients with lcSSc had higher levels of peripheral airway resistance, that is, R5-R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02-0.09) in lcSSc, 0.01 (0.00-0.04) in dcSSc and 0.04 (0.01-0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15-0.56) in lcSSc, 0.20 (0.11-0.29) in dcSSc and 0.18 (0.08-0.30) in healthy controls, and resonant frequency was 10.9 (8.8-14.8) in lcSSc, 9.0 (8.3-11.6) in dcSSc and 9.1 (8.0 13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations. DISCUSSION: This implies that IOS parameters to some extent are related to fibrosis in patients with SSc. PMID- 26672964 TI - Prevalence of PI*Z and PI*S alleles of alpha-1-antitrypsin deficiency in Finland. AB - The prevalence of PI*Z and PI*S alleles of SERPINA1 gene related to alpha-1 antitrypsin deficiency has previously been estimated to be lower in Finland than in the other countries of Northern Europe. The prevalence of PI*M (Malton) has not been studied in Finland before. We determined alpha-1-antitrypsin PI*Z and PI*S and PI*M (Malton) genotypes from a representative population sample. The number of subjects was 6,354 in the PI*S and PI*M (Malton) genotyping. PI*Z genotyping was performed in a subsample of 2,482 subjects. The allele frequencies were PI*Z 19.7/1,000 and PI*S 10.2/1,000. No PI*M (Malton) was found. The number of carriers of PI*Z and PI*S is significantly higher than previously estimated. The prevalences are in line with the findings in the neighboring countries. PMID- 26672962 TI - Application of nitric oxide measurements in clinical conditions beyond asthma. AB - Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma. PMID- 26672965 TI - TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2. AB - The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 A resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2. PMID- 26672967 TI - Cystic Lymhangioma of the Lesser Sac in Adult Presenting with Features of Gastric Outlet Obstruction - A Case Report. AB - Cystic lymphangioma is a paediatric benign tumour, occurs commonly in head and neck region. Adult intraabdominal lymphangiomas are uncommon and only few cases of lesser sac cystic lymphangioma are reported in the literature. We present a case of lesser sac cystic lymphangioma in a 26-year-old lady who presented with features of gastric outlet obstruction. Clinical examination revealed a 10x10 cm firm, non tender, mobile intraabdominal lump in the epigastrium. An upper gastrointestinal endoscopy showed possible external compression at the body of the stomach. Ultrasound demonstrated a multicystic lesion, with internal echoes in one locule. CECT showed a large multiloculated cystic lesion with hyper-dense content in the lesser sac extending up to the left lobe of the liver and indenting the stomach, lesser sac, and upper border of pancreas. On surgical exploration, a 10X8 cm multi cystic lesion with clear fluid was found in the lesser sac very close to the lesser curvature of stomach. Histopathological examination of the excised lesion showed features of cystic lymphangioma. Though very rare, intraabdominal cystic lymphangiomas should be considered in all atypical cases of gastric outlet obstruction. A reasonable knowledge about these benign lesions will aid in establishing the diagnosis and surgical management. PMID- 26672966 TI - Prenatal Cocaine Exposure and Cardiometabolic Disease Risk Factors in 18- to 20 Year-Old African Americans. AB - OBJECTIVE: The long-term effects of prenatal cocaine exposure (PCE) on physical health are largely unknown. No human studies support or refute a relationship between PCE and the long-term risk for cardiovascular and/or metabolic disease. We investigated the association of PCE on primary cardiometabolic disease risk factors in African Americans (AA) aged 18 to 20 years. DESIGN: Cohort, longitudinal, prospective. SETTING: Miami-Dade County, Florida, and the University of Miami Miller School of Medicine/Jackson Memorial Medical Center. PARTICIPANTS: Healthy full-term inner-city AA adolescents (aged 18 to 20 years, n=350) previously enrolled at birth from 1990-1993. MAIN OUTCOME MEASURES: Fasting serum insulin, glucose, lipids, and high-sensitivity C-reactive protein; systolic and diastolic blood pressures; and the components and prevalence of the metabolic syndrome. RESULTS: There were no PCE-associated differences in cardiometabolic disease risk factors including the metabolic syndrome and its individual components in AAs aged 18 to 20 years. CONCLUSIONS: The results of our study do not support an association between PCE and increased cardiometabolic disease risk in AAs aged 18 to 20 years. Whether PCE is associated with cardiovascular or metabolic disease in adulthood would require further investigation. PMID- 26672969 TI - Is pneumoperitoneum the terra ignota in ultrasonography? AB - In most cases, pneumoperitoneum is caused by gastrointestinal perforation, which usually requires surgical treatment. Many authors believe that ultrasound imaging of pneumoperitoneum is at least as effective as conventional radiography, or even that its efficacy is superior. In such a situation, it is imperative to make this modality one of the main tools in the diagnostic arsenal of emergency medicine. This is the main aim of this paper. First, ultrasound anatomy of so-called thoracic-abdominal border is discussed. The equipment requirements emphasize that the diagnostic process can be conducted with the simplest portable US scanner, even without the Doppler mode. The technique of a US examination, the aim of which is to detect, free air in the peritoneal cavity is also simple and conducted with the patients lying down, either in the supine or lateral position. A convex transducer with the frequency of 3.5-5 MHz is applied above the lower intercostal spaces on the right and left side, to the epigastric region below the xiphoid process and in various sites of the abdominal wall. The most effective examination, however, is conducted in the left lateral position via the right intercostal spaces. The differential diagnosis on the right side under the diaphragm should include the presence of a subdiaphragmatic abscess with gas and a hepatic abscess with a similar content as well as transposition of the colon in between the diaphragm and the liver (Chilaiditi syndrome). It seems that the inclusion of a US examination to the E-FAST method in order to detect free gas in the peritoneal cavity is justified since it is a sign of gastrointestinal perforation in numerous cases, and is clinically as relevant as the presence of free fluid. PMID- 26672968 TI - An Update on Helicobacter pylori as the Cause of Gastric Cancer. AB - BACKGROUND: Gastric cancer is the second most common cause of cancer deaths worldwide. The vast majority of gastric cancers are inflammation-related cancers caused by infection with Helicobacter pylori. H. pylori-induced oxidative stress damages DNA, resulting in genetic instability. In addition, H. pylori itself can cause DNA damage and epigenetic changes that trigger genetic instability and neoplastic transformation. SUMMARY: H. pylori strain-specific components act in combination with host factors and environmental and dietary factors to greatly enhance the inflammatory response and thus the cancer risk. Variations in several key factors, such as the cag pathogenicity island and the VacA protein, can trigger a greater inflammatory response in host cells. Genetic polymorphisms in the host such as in the IL-1beta gene, and chromosomes 9p21.3 and 10q23 also play a contributing role. Finally, diet is a major external factor that modulates the risk of gastric cancer. KEY MESSAGE: The majority of gastric cancers are inflammation-related cancers caused by infection with H. pylori. Eradication of H. pylori is important for the prevention and treatment of gastric cancer. PRACTICAL IMPLICATIONS: H. pylori eradication results in healing of gastritis and prevention of further H. pylori-induced genetic damage. Eradication of H. pylori prior to development of atrophic gastritis can prevent the development of gastric cancer. Japan has undertaken a nationwide program to identify and eliminate H. pylori, along with surveillance for those who underwent H. pylori eradication too late to eliminate cancer risk. Population-wide eradication of H. pylori will result in gastric cancer becoming a vanishingly rare disease. PMID- 26672970 TI - Errors and mistakes in ultrasound diagnostics of the thyroid gland. AB - Ultrasound examination of the thyroid gland permits to evaluate its size, echogenicity, margins, and stroma. An abnormal ultrasound image of the thyroid, accompanied by other diagnostic investigations, facilitates therapeutic decision making. The ultrasound image of a normal thyroid gland does not change substantially with patient's age. Nevertheless, erroneous impressions in thyroid imaging reports are sometimes encountered. These are due to diagnostic pitfalls which cannot be prevented by either the continuing development of the imaging equipment, or the growing experience and skill of the practitioners. Our article discusses the most common mistakes encountered in US diagnostics of the thyroid, the elimination of which should improve the quality of both the ultrasound examination itself and its interpretation. We have outlined errors resulting from a faulty examination technique, the similarity of the neighboring anatomical structures, and anomalies present in the proximity of the thyroid gland. We have also pointed out the reasons for inaccurate assessment of a thyroid lesion image, such as having no access to clinical data or not taking them into account, as well as faulty qualification for a fine needle aspiration biopsy. We have presented guidelines aimed at limiting the number of misdiagnoses in thyroid diseases, and provided sonograms exemplifying diagnostic mistakes. PMID- 26672971 TI - Signalling to the nucleus under the control of light and small molecules. AB - One major regulatory mechanism in cell signalling is the spatio-temporal control of the localization of signalling molecules. We synthetically designed an entire cell signalling pathway, which allows controlling the transport of signalling molecules from the plasma membrane to the nucleus, by using light and small molecules. PMID- 26672972 TI - Nonlinear anisotropic deformation behavior of a graphene monolayer under uniaxial tension. AB - Based on first principle calculations, a graphene monolayer shows a complicated deformation behavior under uniaxial tension. The maximum stress of graphene is reached when the bond stretching ratio is far less than its breaking value, which means that graphene shows the typical "ductile-like" behavior but not the conventionally considered "brittle-like" behavior. Although the graphene monolayer shows isotropic behavior in strength, it is strongly anisotropic in deformation (i.e., the ultimate strain is highly different along the different directions). Under uniaxial tension along the zigzag/armchair direction, the overall deformation is only supported by the C-C bonds in one orientation, whereas the C-C bonds in the other orientation and the C-C-C bond angle have almost no contribution, which cannot be correctly predicted by the empirical potential simulations. The complicated bond deformation means that the conventional constitutive model (sigma = Eepsilon + Depsilon(2)) cannot accurately describe the tensile behavior of the graphene monolayer. According to the bond deformation under uniaxial tension, graphene can be simplified as a spring-network including both nonlinear springs (resisting both the tensile and compressive load) and a very strong compressive angle-spring (resisting the decrease of the C-C-C bond angle). PMID- 26672973 TI - Higher serum phosphorus is associated with catabolic/anabolic imbalance in heart failure. AB - BACKGROUND: A higher serum phosphate level is associated with worse outcome. Energy-demanding intracellular transport of phosphate is needed to secure anion bioavailability. In heart failure (HF), energy starvation may modify intracellular and serum levels of phosphate. We analysed determinants of serum phosphates in HF and assessed if catabolic/anabolic balance (CAB) was associated with elevation of serum phosphate. METHODS: We retrospectively reviewed data from 1029 stable patients with HF and have calculated negative (loss) and positive (gain) components of weight change from the onset of HF till index date. The algebraic sum of these components was taken as CAB. The univariate and multivariable predictors of serum phosphorus were calculated. In quintiles of CAB, we have estimated odds ratios for serum phosphorus above levels previously identified to increase risk of mortality. As a reference, we have selected a CAB quintile with similar loss and gain. RESULTS: Apart from sex, age, and kidney function, we identified serum sodium, N-terminal fragment of pro-brain-type natriuretic peptide, and CAB as independent predictors of serum phosphorus. The odds for serum phosphorus above thresholds found in literature to increase risk were highest in more catabolic patients. In most catabolic quintile relative to neutral balance, the odds across selected phosphorus thresholds rose, gradually peaking at 1.30 mmol/L with a value of 3.29 (95% confidence interval: 2.00-5.40, P < 0.0001) in an unadjusted analysis and 2.55 (95% confidence interval: 1.38 2.72, P = 0.002) in a fully adjusted model. CONCLUSIONS: Metabolic status is an independent determinant of serum phosphorus in HF. Higher catabolism is associated with serum phosphorus above mortality risk-increasing thresholds. PMID- 26672974 TI - Laryngo-tracheal ultrasonography to confirm correct endotracheal tube and laryngeal mask airway placement. AB - Waveform capnography was recommended as the most reliable method to confirm correct endotracheal tube or laryngeal mask airway placements. However, capnography may be unreliable during cardiopulmonary resuscitation and during low flow states. It may lead to an unnecessary removal of a well-placed endotracheal tube, re-intubation and interruption of chest compressions. Real-time upper airway (laryngo-tracheal) ultrasonography to confirm correct endotracheal tube placement was shown to be very useful in cadaveric models and during emergency intubation. Tracheal ultrasonography does not interrupt chest compressions and is not affected by low pulmonary flow or airway obstruction, but is limited by ultrasonography scattering and acoustic artifacts generated in air - mucosa interfaces. Sonographic upper airway assessment emerges as a rapid and easily available method to predict difficult intubation, to assess the laryngeal and hypopharyngeal size and visualize the position of the laryngeal mask airway in situ. This study demonstrates that the replacement of air with saline in endotracheal tube or laryngeal mask airway cuffs and the use of the contrast agents enables detection of cuffs in the airway. It also allows visualization of the surrounding structures or tissues as the ultrasound beam can be transmitted through the fluid - filled cuffs without being reflected from air - mucosal interfaces. PMID- 26672976 TI - Preparation of alpha1- and alpha2-isomers of mono-Ru-substituted Dawson-type phosphotungstates with an aqua ligand and comparison of their redox potentials, catalytic activities, and thermal stabilities with Keggin-type derivatives. AB - Both the alpha1- and the alpha2-isomers of mono-ruthenium (Ru)-substituted Dawson type phosphotungstates with terminal aqua ligands, [alpha1 P2W17O61Ru(III)(H2O)](7-) (alpha1-RuH2O) and [alpha2-P2W17O61Ru(III)(H2O)](7-) (alpha2-RuH2O), were prepared in pure form by cleavage of the Ru-S bond of the corresponding DMSO derivatives, [alpha1-P2W17O61Ru(DMSO)](8-) (alpha1-RuDMSO) and [alpha2-P2W17O61Ru(DMSO)](8-) (alpha2-RuDMSO), respectively. Redox studies indicated that alpha1-RuH2O and alpha2-RuH2O show proton-coupled electron transfer (PCET), and the Ru(III)(H2O) species was reversibly reduced to Ru(II)(H2O) species and oxidized to Ru(IV)([double bond, length as m-dash]O) species and further to Ru(V)([double bond, length as m-dash]O) species in aqueous solution depending on the pH. Their redox potentials and thermal stabilities were compared with those of the corresponding alpha-Keggin-type derivatives ([alpha XW11O39Ru(H2O)](n-); X = Si(4+) (n = 5), Ge(4+) (n = 5), or P(5+) (n = 4)). The basic electronic and redox features of Ru(L)-substituted Keggin- and Dawson-type heteropolytungstates (with L = H2O or O(2-)) were analyzed by means of density functional calculations. Similar to the corresponding alpha-Keggin-type derivatives, both alpha1-RuH2O and alpha2-RuH2O show catalytic activity for water oxidation. PMID- 26672975 TI - Secreted multifunctional Glyceraldehyde-3-phosphate dehydrogenase sequesters lactoferrin and iron into cells via a non-canonical pathway. AB - Lactoferrin is a crucial nutritionally important pleiotropic molecule and iron an essential trace metal for all life. The current paradigm is that living organisms have evolved specific membrane anchored receptors along with iron carrier molecules for regulated absorption, transport, storage and mobilization of these vital nutrients. We present evidence for the existence of non-canonical pathway whereby cells actively forage these vital resources from beyond their physical boundaries, by secreting the multifunctional housekeeping enzyme Glyceraldehyde-3 phosphate dehydrogenase (GAPDH) into the extracellular milieu. This effect's an autocrine/paracrine acquisition of target ligand into the cell. Internalization by this route is extensively favoured even by cells that express surface receptors for lactoferrin and involves urokinase plasminogen activator receptor (uPAR). We also demonstrate the operation of this phenomenon during inflammation, as an arm of the innate immune response where lactoferrin denies iron to invading microorganisms by chelating it and then itself being sequestered into surrounding host cells by GAPDH. PMID- 26672977 TI - Choledocholithiasis diagnostics - endoscopic ultrasound or endoscopic retrograde cholangiopancreatography? AB - It is estimated that 3.4% of patients qualified for cholecystectomy due to cholelithiasis have a coexisting choledocholithiasis. For decades, endoscopic ascending retrograde cholangiopancreatography has been the golden diagnostic standard in cases of suspected choledocholithiasis. The method is associated with a relatively high rate of complications, including acute pancreatitis, the incidence of which is estimated to range between 0.74% and 1.86%. The mechanism of this ERCP-induced complication is not fully understood, although factors increasing the risk of acute pancreatitis, such as sphincter of Oddi dysfunction, previous acute pancreatitis, narrow bile ducts or difficult catheterization of Vater's ampulla are known. It has been suggested to discontinue the diagnostic endoscopic retrograde ascending cholangiopancreatography and replace it with endoscopic ultrasonography due to possible and potentially dangerous complications. Endoscopic ultrasonography has sensitivity of 94% and specificity of 95% regardless of gallstone diameter, as opposed to magnetic resonance cholangiography. However, both of these parameters depend on the experience of the performing physician. The use of endoscopic ultrasonography allows to limit the number of performed endoscopic retrograde cholangiopancreatography procedures by more than 2/3. Ascending endoscopic retrograde cholangiopancreatography combined with an endoscopic incision into the Vater's ampulla followed by a mechanical evacuation of stone deposits from the ducts still remains a golden standard in the treatment of choledocholithiasis. Despite some limitations such as potentially increased treatment costs as well as the necessity of the procedure to be performed by a surgeon experienced in both endoscopic retrograde cholangiopancreatography as well as endoscopic ultrasonography, the diagnostic endoscopic ultrasonography followed by a simultaneous endoscopic retrograde cholangiopancreatography aimed at gallstone removal is the most efficient diagnostic and therapeutic management scheme in cases of suspected choledocholithiasis. PMID- 26672978 TI - Sex-specific consequences of an induced immune response on reproduction in a moth. AB - BACKGROUND: Immune response induction benefits insects in combatting infection by pathogens. However, organisms have a limited amount of resources available and face the dilemma of partitioning resources between immunity and other life history traits. Since males and females differ in their life histories, sex specific resource investment strategies to achieve an optimal immune response following an infection can be expected. We investigated immune response induction of females and males of Heliothis virescens in response to the entomopathogenic bacterium Serratia entomophila, and its effects on mating success and the female sexual signal. RESULTS: We found that females had higher expression levels of immune-related genes after bacterial challenge than males. However, males maintained a higher baseline expression of immune-related genes than females. The increased investment in immunity of female moths was negatively correlated with mating success and the female sexual signal. Male mating success was unaffected by bacterial challenge. CONCLUSIONS: Our results show that the sexes differed in their investment strategies: females invested in immune defense after a bacterial challenge, indicating facultative immune deployment, whereas males had higher baseline immunity than females, indicating immune maintenance. Interestingly, these differences in investment were reflected in the mate choice assays. As female moths are the sexual signallers, females need to invest resources in their attractiveness. However, female moths appeared to invest in immunity at the cost of reproductive effort. PMID- 26672979 TI - Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: history, current applications, and future directions. AB - Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department. PMID- 26672981 TI - Manipulation and measurement of pH sensitive metal-ligand binding using electrochemical proton generation and metal detection. AB - Generator-detector electrodes can be used to both perturb and monitor pH dependant metal-ligand binding equilibria, in situ. In particular, protons generated at the generator locally influence the speciation of metal (Cu(2+)) in the presence of ligand (triethylenetetraamine), with the detector employed to monitor, in real time, free metal (Cu(2+)) concentrations. PMID- 26672980 TI - Physical activity before and after breast cancer diagnosis and survival - the Norwegian women and cancer cohort study. AB - BACKGROUND: The main aim of this study was to investigate pre- and post diagnostic physical activity (PA) levels, as well as changes in pre- and post diagnostic PA levels, and their association with all-cause and breast cancer specific mortality in women with breast cancer. Our study will add to the knowledge on whether a modifiable behavior such as PA can improve survival. METHODS: We included 1,327 women with breast cancer from the population-based Norwegian Women and Cancer study, which enrolled women from 1991 to 2003. Breast cancer cases were identified through linkage to the Cancer Registry of Norway; date and cause of death were obtained from the National Register for Causes of Death through 31 December 2012. Self-reported pre- and post-diagnostic PA levels were assessed, and Cox proportional hazard regression and spline regression were used to evaluate the associations. RESULTS: Pre-diagnostic PA levels were not associated with all-cause or breast cancer-specific mortality. Post-diagnostic PA levels were associated with a significant trend (P<0.001) of decreased all-cause and breast cancer-specific mortality, which was stronger among older women (aged 50-74 years) and did not differ across categories of body mass index. All-cause mortality (hazard ratio [HR]=1.76, 95% confidence interval [CI] 1.21-2.56) and breast cancer-specific mortality (HR=2.05, 95% CI 1.35-3.10) increased among women who reduced their post-diagnostic PA level. These values were similar among women whose maintained an inactive PA level pre- and post-diagnosis. CONCLUSION: Overall, we observed a dose-response trend, with an inverse association between increased post-diagnostic PA level and all-cause and breast cancer-specific mortality, as well as a higher mortality risk among women who reduced their post diagnostic PA levels. Our results are very promising for women with breast cancer, and indicate that health care professionals should consider adding PA as a part of primary cancer treatment. PMID- 26672982 TI - Graphic Warning Labels Elicit Affective and Thoughtful Responses from Smokers: Results of a Randomized Clinical Trial. AB - OBJECTIVE: Observational research suggests that placing graphic images on cigarette warning labels can reduce smoking rates, but field studies lack experimental control. Our primary objective was to determine the psychological processes set in motion by naturalistic exposure to graphic vs. text-only warnings in a randomized clinical trial involving exposure to modified cigarette packs over a 4-week period. Theories of graphic-warning impact were tested by examining affect toward smoking, credibility of warning information, risk perceptions, quit intentions, warning label memory, and smoking risk knowledge. METHODS: Adults who smoked between 5 and 40 cigarettes daily (N = 293; mean age = 33.7), did not have a contra-indicated medical condition, and did not intend to quit were recruited from Philadelphia, PA and Columbus, OH. Smokers were randomly assigned to receive their own brand of cigarettes for four weeks in one of three warning conditions: text only, graphic images plus text, or graphic images with elaborated text. RESULTS: Data from 244 participants who completed the trial were analyzed in structural-equation models. The presence of graphic images (compared to text-only) caused more negative affect toward smoking, a process that indirectly influenced risk perceptions and quit intentions (e.g., image->negative affect->risk perception->quit intention). Negative affect from graphic images also enhanced warning credibility including through increased scrutiny of the warnings, a process that also indirectly affected risk perceptions and quit intentions (e.g., image->negative affect->risk scrutiny->warning credibility >risk perception->quit intention). Unexpectedly, elaborated text reduced warning credibility. Finally, graphic warnings increased warning-information recall and indirectly increased smoking-risk knowledge at the end of the trial and one month later. CONCLUSIONS: In the first naturalistic clinical trial conducted, graphic warning labels are more effective than text-only warnings in encouraging smokers to consider quitting and in educating them about smoking's risks. Negative affective reactions to smoking, thinking about risks, and perceptions of credibility are mediators of their impact. TRIAL REGISTRATION: Clinicaltrials.gov NCT01782053. PMID- 26672983 TI - An Integrated Coral Reef Ecosystem Model to Support Resource Management under a Changing Climate. AB - Millions of people rely on the ecosystem services provided by coral reefs, but sustaining these benefits requires an understanding of how reefs and their biotic communities are affected by local human-induced disturbances and global climate change. Ecosystem-based management that explicitly considers the indirect and cumulative effects of multiple disturbances has been recommended and adopted in policies in many places around the globe. Ecosystem models give insight into complex reef dynamics and their responses to multiple disturbances and are useful tools to support planning and implementation of ecosystem-based management. We adapted the Atlantis Ecosystem Model to incorporate key dynamics for a coral reef ecosystem around Guam in the tropical western Pacific. We used this model to quantify the effects of predicted climate and ocean changes and current levels of current land-based sources of pollution (LBSP) and fishing. We used the following six ecosystem metrics as indicators of ecosystem state, resilience and harvest potential: 1) ratio of calcifying to non-calcifying benthic groups, 2) trophic level of the community, 3) biomass of apex predators, 4) biomass of herbivorous fishes, 5) total biomass of living groups and 6) the end-to-start ratio of exploited fish groups. Simulation tests of the effects of each of the three drivers separately suggest that by mid-century climate change will have the largest overall effect on this suite of ecosystem metrics due to substantial negative effects on coral cover. The effects of fishing were also important, negatively influencing five out of the six metrics. Moreover, LBSP exacerbates this effect for all metrics but not quite as badly as would be expected under additive assumptions, although the magnitude of the effects of LBSP are sensitive to uncertainty associated with primary productivity. Over longer time spans (i.e., 65 year simulations), climate change impacts have a slight positive interaction with other drivers, generally meaning that declines in ecosystem metrics are not as steep as the sum of individual effects of the drivers. These analyses offer one way to quantify impacts and interactions of particular stressors in an ecosystem context and so provide guidance to managers. For example, the model showed that improving water quality, rather than prohibiting fishing, extended the timescales over which corals can maintain high abundance by at least 5-8 years. This result, in turn, provides more scope for corals to adapt or for resilient species to become established and for local and global management efforts to reduce or reverse stressors. PMID- 26672985 TI - Immobilization of myoglobin on Au nanoparticle-decorated carbon nanotube/polytyramine composite as a mediator-free H2O2 and nitrite biosensor. AB - A novel composite film was designed for use as a highly selective mediator-free amperometric biosensor, and a method was created for accomplishing direct electrochemistry of myoglobin on a multi-walled carbon nanotube and tyramine modified composite decorated with Au nanoparticles on a glassy carbon electrode. The ultraviolet-visible and electrochemical impedance spectroscopy results showed that myoglobin retained its native conformation in the interaction with Au-PTy-f MWCNT. The surface coverage of Mb-heme-Fe((II)/(III)) immobilized on Au-PTy-f MWCNT and the heterogeneous electron-transfer rate constant were 2.12 * 10(-9) mol cm(-2) and 4.86 s(-1), respectively, indicating a higher loading capacity of the nanocomposite for direct electron transfer of Mb onto the electrode surface. The proposed Mb/Au-PTy-f-MWCNT biofilm exhibited excellent electrocatalytic behavior toward the reduction of H2O2 and the oxidation of nitrite with linear ranges of 2 to 5000 MUM and 1 to 8000 MUM and lower detection limits of 0.01 MUM and 0.002 MUM, respectively. An apparent Michaelis-Menten constant of 0.12 mM indicated that the Mb immobilized on the Au-PTy-f-MWCNT film retained its native activity. This biosensor can be successfully applied to detect H2O2 and nitrite in disinfectant cream, eye drops, pickle juice, and milk samples. PMID- 26672984 TI - Purification, Cloning and Immuno-Biochemical Characterization of a Fungal Aspartic Protease Allergen Rhi o 1 from the Airborne Mold Rhizopus oryzae. AB - BACKGROUND: Fungal allergy is considered as serious health problem worldwide and is increasing at an alarming rate in the industrialized areas. Rhizopus oyzae is a ubiquitously present airborne pathogenic mold and an important source of inhalant allergens for the atopic population of India. Here, we report the biochemical and immunological features of its 44 kDa sero-reactive aspartic protease allergen, which is given the official designation 'Rhi o 1'. METHOD: The natural Rhi o 1 was purified by sequential column chromatography and its amino acid sequence was determined by mass spectrometry and N-terminal sequencing. Based on its amino acid sequence, the cDNA sequence was identified, cloned and expressed to produce recombinant Rhi o 1. The allergenic activity of rRhi o 1 was assessed by means of its IgE reactivity and histamine release ability. The biochemical property of Rhi o 1 was studied by enzyme assay. IgE-inhibition experiments were performed to identify its cross-reactivity with the German cockroach aspartic protease allergen Bla g 2. For precise characterization of the cross-reactive epitope, we used anti-Bla g 2 monoclonal antibodies for their antigenic specificity towards Rhi o 1. A homology based model of Rhi o 1 was built and mapping of the cross-reactive conformational epitope was done using certain in silico structural studies. RESULTS: The purified natural nRhi o 1 was identified as an endopeptidase. The full length allergen cDNA was expressed and purified as recombinant rRhi o 1. Purified rRhi o 1 displayed complete allergenicity similar to the native nRhi o 1. It was recognized by the serum IgE of the selected mold allergy patients and efficiently induced histamine release from the sensitized PBMC cells. This allergen was identified as an active aspartic protease functional in low pH. The Rhi o 1 showed cross reactivity with the cockroach allergen Bla g 2, as it can inhibit IgE binding to rBla g 2 up to certain level. The rBla g 2 was also found to cross-stimulate histamine release from the effector cells sensitized with anti-Rhi o 1 serum IgE. This cross reactivity was found to be mediated by a common mAb4C3 recognizable conformational epitope. Bioinformatic studies revealed high degree of structural resemblances between the 4C3 binding sites of both the allergens. CONCLUSION/SIGNIFICANCE: The present study reports for the first time anew fungal aspartic protease allergen designated as Rhi o 1, which triggers IgE-mediated sensitization leading to various allergic diseases. Here we have characterized the recombinant Rhi o 1 and its immunological features including cross-reactive epitope information that will facilitate the component-resolved diagnosis of mold allergy. PMID- 26672986 TI - Diiron centre mutations in Ciona intestinalis alternative oxidase abolish enzymatic activity and prevent rescue of cytochrome oxidase deficiency in flies. AB - The mitochondrial alternative oxidase, AOX, carries out the non proton-motive re oxidation of ubiquinol by oxygen in lower eukaryotes, plants and some animals. Here we created a modified version of AOX from Ciona instestinalis, carrying mutations at conserved residues predicted to be required for chelation of the diiron prosthetic group. The modified protein was stably expressed in mammalian cells or flies, but lacked enzymatic activity and was unable to rescue the phenotypes of flies knocked down for a subunit of cytochrome oxidase. The mutated AOX transgene is thus a potentially useful tool in studies of the physiological effects of AOX expression. PMID- 26672988 TI - Correction: Selection Mosaic Exerted by Specialist and Generalist Herbivores on Chemical and Physical Defense of Datura stramonium. PMID- 26672987 TI - Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation. AB - INTRODUCTION: There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs). METHODS: Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR). RESULTS: Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), and interleukin 8 (IL-8) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for PTGS1 and ALOX12. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E2 (PGE2)/ARA for PTGS1 and 12 hydroxyeicosatetraenoic acid (12-HETE)/ARA for ALOX12) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in PTGS1 gene expression was highly positively correlated with ALOX12 gene expression but not with PTGS2, whereas IL 8 and PTGS2 were positively correlated. CONCLUSIONS: The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of PTGS1 and ALOX12 regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals. TRIAL REGISTRATION: clinicaltrials.gov NCT01838239. PMID- 26672989 TI - Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study. AB - MOTIVATION: Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. METHODS: In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. RESULTS AND CONCLUSION: The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID- 26672990 TI - Legume-Cereal Intercropping Improves Forage Yield, Quality and Degradability. AB - Intercropping legume with cereal is an extensively applied planting pattern in crop cultivation. However, forage potential and the degradability of harvested mixtures from intercropping system remain unclear. To investigate the feasibility of applying an intercropping system as a forage supply source to ruminants, two consecutive experiments (experiments 1 and 2) involving a field cultivation trial and a subsequent in vivo degradable experiment were conducted to determine the forage production performance and the ruminally degradable characteristics of a harvested mixture from an alfalfa/corn-rye intercropping system. In experiment 1, the intercropping system was established by alternating alfalfa and corn or rye with a row ratio of 5:2. Dry matter (DM) and nutrient yields were determined. In experiment 2, forages harvested from the different treatments were used as feedstuff to identify nutrient degradation kinetics and distribution of components between the rapidly degradable (a), potentially degradable (b) and the degradation rate constant (c) of 'b' fraction by in sacco method in Small-Tail Han wether Sheep. The intercropping system of alfalfa and corn-rye provided higher forage production performance with net increases of 9.52% and 34.81% in DM yield, 42.13% and 16.74% in crude protein (CP) yield, 25.94% and 69.99% in degradable DM yield, and 16.96% and 5.50% in degradable CP yield than rotation and alfalfa sole cropping systems, respectively. In addition, the harvest mixture from intercropping system also had greater 'a' fraction, 'b' fraction, 'c' values, and effective degradability (E value) of DM and CP than corn or rye hay harvested from rotation system. After 48-h exposure to rumen microbes, intercropping harvest materials were degraded to a higher extent than separately degraded crop stems from the sole system as indicated by visual microscopic examination with more tissues disappeared. Thus, the intercropping of alfalfa and corn-rye exhibited a greater forage production potential, and could be applied as forage supply source for ruminants. The improved effective degradability of harvest mixture material could be attributed to greater degradable components involving the rapidly degradable fractions (a), potentially degradable (b) fractions, and degradable rate constant PMID- 26672992 TI - Challenges to the surveillance of non-communicable diseases--a review of selected approaches. AB - BACKGROUND: The rising global burden of non-communicable diseases (NCDs) necessitates the institutionalization of surveillance systems to track trends and evaluate interventions. However, NCD surveillance capacities vary across high- and low- and middle-income countries. The objective of the review was to analyse existing literature with respect to structures of health facility-based NCD surveillance systems and the lessons low- and middle-income countries can learn in setting up and running these systems. METHODS: A literature review was conducted using Pub Med, Web of Knowledge and WHOLIS databases to identify citations published in English language between 1993 and 2013. In total, 20 manuscripts met inclusion criteria: 12 studies were analysed in respect to the surveillance approach, eight supporting documents in respect to general and regional challenges in NCD surveillance. RESULTS: Eleven of the 12 studies identified were conducted in high-income countries. Five studies had a single disease focus, three a multiple NCD focus and three covered communicable as well as non-communicable diseases. Nine studies were passive assisted sentinel surveillance systems, of which six focused on the primary care level and three had additional active surveillance components, i.e., population-based surveys. The supporting documents reveal that NCD surveillance is rather limited in most low- and middle-income countries despite the increasing disease burden and its socioeconomic impact. Major barriers include institutional surveillance capacities and hence data availability. CONCLUSIONS: The review suggests that given the complex system requirements, multiple surveillance approaches are necessary to collect comprehensive information for effective NCD surveillance. Sentinel augmented facility-based surveillance, preferably supported by population-based surveys, can provide improved evidence and help budget scarce resources. PMID- 26672991 TI - Epigenetic control of phospholipase A2 receptor expression in mammary cancer cells. AB - BACKGROUND: It has recently been proposed that the M-type phospholipase A2 receptor (PLA2R1) acts as a tumour suppressor in certain malignancies including mammary cancer. Considering that DNA methylation is an important regulator of gene transcription during carcinogenesis, in the current study we analyzed the PLA2R1 expression, PLA2R1 promoter methylation, and selected micro RNA (miRNA) levels in normal human mammary epithelial cells (HMEC) and cancer cell lines. METHODS: Levels of PLA2R1 and DNA methyltransferases (DNMT) specific mRNA were determined using real-time RT-PCR. Methylation specific-high resolution melting (MS-HRM) analysis was utilized to quantify the methylation degree of selected CpG sites localized in the promoter region of the PLA2R1 gene. Expression of miRNA was tested using miScript Primer Assay system. RESULTS: Nearly complete methylation of the analyzed PLA2R1 promoter region along with PLA2R1 gene silencing was identified in MDA-MB-453 mammary cancer cells. In MCF-7 and BT-474 mammary cancer cell lines, a higher DNA methylation degree and reduced PLA2R1 expression were found in comparison with those in normal HMEC. Synergistic effects of demethylating agent (5-aza-2'-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) on PLA2R1 transcription in MDA-MB-453 cells confirmed the importance of DNA methylation and histone modification in the regulation of the PLA2R1 gene expression in mammary cells. Furthermore, significant positive correlation between the expression of DNMT1 and PLA2R1 gene methylation and negative correlation between the cellular levels of hsa-mir-141, -181b, and -181d 1 and the expression of PLA2R1 were identified in the analyzed cells. Analysis of combined z-score of miR-23b, -154 and -302d demonstrated a strong and significant positive correlation with PLA2R1 expression. CONCLUSIONS: Our data indicate that (i) PLA2R1 expression in breast cancer cells is controlled by DNA methylation and histone modifications, (ii) hypermethylation of the PLA2R1 promoter region is associated with up-regulation of DNMT1, and (iii) hsa-miR-23b, -154, and -302d, as well as hsa-miR-141, -181b, and -181d-1 are potential candidates for post transcriptional regulation of PLA2R1 expression in mammary cancer cells. PMID- 26672994 TI - Are you pharmiscuous? Take our quiz! PMID- 26672995 TI - Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis. AB - BACKGROUND: In multiple sclerosis (MS), pathophysiology of fatigue is only partially known. OBJECTIVE: The aim of this study was to investigate whether the attention-induced modulation on short- and long-term cortical plasticity mechanisms in primary motor area (M1) is abnormal in patients with MS-related fatigue. METHODS: All participants underwent 5-Hz repetitive transcranial magnetic stimulation (rTMS), reflecting short-term plasticity, and paired associative stimulation (PAS), reflecting long-term plasticity, and were asked to focus their attention on the hand contralateral to the M1 stimulated. A group of age-matched healthy subjects acted as control. RESULTS: In patients with MS, 5-Hz rTMS and PAS failed to induce the normal increase in motor-evoked potential (MEP). During the attention-demanding condition, 5-Hz rTMS- and PAS-induced responses differed in patients with MS with and without fatigue. Whereas in patients with fatigue neither technique induced the attention-induced MEP increase, in patients without fatigue they both increased the MEP response, although they did so less efficiently than in healthy subjects. Attention-induced changes in short-term cortical plasticity inversely correlated with fatigue severity. CONCLUSION: Short-term and long-term plasticity mechanisms are abnormal in MS possibly owing to widespread changes in ion-channel expression. Fatigue in MS reflects disrupted cortical attentional networks related to movement control. PMID- 26672996 TI - Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal appearing gray matter in multiple sclerosis. AB - BACKGROUND: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. OBJECTIVE: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. METHODS: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. RESULTS: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. CONCLUSION: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects. PMID- 26672993 TI - Multifactorial determinants of cognition - Thyroid function is not the only one. AB - BACKGROUND: Since the 1960s hypothyroidism together with iodine deficiency have been considered to be a principal determinant of cognition development. Following iodine supplementation programs and improved treatment options for hypothyroidism this relation might not be valid in 2015. On the other hand neurosciences have added different inputs also related to cognition. SCOPE OF REVIEW: We will examine the characteristics of the original and current publications on thyroid function and cognition and also add some general determinants of intelligence and cognition. One central issue for us is the relation of stress to cognition knowing that both physical and psychological stress, are frequent elements in subjects with thyroid dysfunction. We have considered a special type of stress called pre-natal stress which can influence cognitive functions. Fear and anxiety can be intermingled requiring mechanisms of fear extinction. MAJOR CONCLUSIONS: Recent studies have failed to show an influence of thyroid medication during pregnancy on intellectual development. Neuroscience offers a better explanation of cognition than hypothyroidism and iodine deficiency. Additional factors relevant to cognition are nutrition, infection, prenatal stress, and early life stress. In turn stress is related to low magnesium levels. Magnesium supplementation can correct both latent hypothyroidism and acquired mild cognitive deficits. GENERAL SIGNIFICANCE: Cognition is a complex process that depends on many determinants and not only on thyroid function. Magnesium deficiency appears to be a basic mechanism for changes in thyroid function as well as of cognition. PMID- 26672997 TI - A process evaluation of a home-based occupational therapy intervention for Parkinson's patients and their caregivers performed alongside a randomized controlled trial. AB - OBJECTIVE: To evaluate fidelity, treatment enactment and the experiences of an occupational therapy intervention in Parkinson's disease, to identify factors that affect intervention delivery and benefits. DESIGN: Mixed methods alongside a randomized controlled trial. SUBJECTS: These include 124 home-dwelling Parkinson's disease patients and their primary caregivers (recipients), and 18 occupational therapists. INTERVENTION: Ten-week home-based intervention according to the Dutch guidelines for occupational therapy in Parkinson's disease. MAIN MEASURES: Data were collected on intervention dose, protocol process, content of treatment (fidelity), offered and performed strategies (treatment enactment), and recipients' experiences. Therapists' experiences were collected through case note analyses and focus group interviews. RESULTS: Mean intervention dose was 9.3 (SD 2.3) hours. Mean protocol process adherence was high (93%; SD 9%), however the intervention did not (fully) address the goal for 268 of 617 treatment goals. Frequencies of offered and performed strategies appeared similar, apart from 'using other tools and materials' which showed a drop from 279 advised to 149 used. The recipients were satisfied overall with the intervention (mean score 8 out of 10). The therapists noted positive or negative influencing factors on both process and benefits: the research context, the socio-political healthcare context, the recipients' personal and contextual factors, and the therapists' competence. CONCLUSION: We found some prerequisite factors in equipment provision and available dose important for treatment delivery. Other elicited factors related to, or affected, the required professional competencies and tools to tailor interventions to the complexity of interacting personal and contextual factors of patients and caregivers. PMID- 26672998 TI - Effectiveness of a group-based self-management program for people with chronic fatigue syndrome: a randomized controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of a group-based self-management program for people with chronic fatigue syndrome. DESIGN: A randomized controlled trial. SETTING: Four mid-sized towns in southern Norway and two suburbs of Oslo. SUBJECTS: A total of 137 adults with chronic fatigue syndrome. INTERVENTION: A self-management program including eight biweekly meetings of 2.5 hours duration. The control group received usual care. MAIN MEASURES: Primary outcome measure: Medical Outcomes Study-Short Form-36 physical functioning subscale. SECONDARY OUTCOME MEASURES: Fatigue severity scale, self-efficacy scale, physical and mental component summary of the Short Form-36, and the illness cognition questionnaire (acceptance subscale). Assessments were performed at baseline, and at six-month and one-year follow-ups. RESULTS: At the six-month follow-up, a significant difference between the two groups was found concerning fatigue severity ( p = 0.039) in favor of the control group, and concerning self-efficacy in favor of the intervention group ( p = 0.039). These significant differences were not sustained at the one-year follow-up. No significant differences were found between the groups concerning physical functioning, acceptance, and health status at any of the measure points. The drop-out rate was 13.9% and the median number of sessions attended was seven (out of eight). CONCLUSIONS: The evaluated self-management program did not have any sustained effect, as compared with receiving usual care. PMID- 26672999 TI - Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease. AB - BACKGROUND/AIMS: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. METHODS: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. RESULTS: Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). CONCLUSION: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD. PMID- 26673001 TI - G-Links: a gene-centric link acquisition service. AB - With the availability of numerous curated databases, researchers are now able to efficiently use the multitude of biological data by integrating these resources via hyperlinks and cross-references. A large proportion of bioinformatics research tasks, however, may include labor-intensive tasks such as fetching, parsing, and merging datasets and functional annotations from distributed multi domain databases. This data integration issue is one of the key challenges in bioinformatics. We aim to solve this problem with a service named G-Links, 1) by gathering resource URI information from 130 databases and 30 web services in a gene-centric manner so that users can retrieve all available links about a given gene, 2) by providing RESTful API for easy retrieval of links including facet searching based on keywords and/or predicate types, and 3) by producing a variety of outputs as visual HTML page, tab-delimited text, and in Semantic Web formats such as Notation3 and RDF. G-Links as well as other relevant documentation are available at http://link.g-language.org/. PMID- 26673000 TI - Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. AB - Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali /quantitative modification of upper gastrointestinal microbiota and clinical response. PMID- 26673002 TI - Open-Framework Structures of Anhydrous Sr(CF3COO)2 and Ba(CF3COO)2. AB - Anhydrous Sr(CF3COO)2 and Ba(CF3COO)2 open-framework structures featuring three dimensional connectivity of metal-oxygen polyhedra were crystallized from a mixture of water and CF3COOH. Crystallization was induced via evaporation of the solvent mixture under a dry nitrogen flow. This approach differs from that routinely employed for crystallization of metal trifluoroacetates, which achieves solvent evaporation by heating under air and yields hydrated salts. Thermogravimetric and differential thermal analysis as well as single-crystal and synchrotron powder X-ray diffraction were employed to characterize the alkaline earth trifluoroacetate products. Neither thermal analysis nor single-crystal X ray diffraction detected the presence of crystallization water molecules, demonstrating these trifluoroacetates can be obtained in anhydrous form. Single crystal X-ray diffraction studies showed that Sr(CF3COO)2 and Ba(CF3COO)2 are isostructural and crystallize in the rhombohedral R3 space group. Both compounds belong to the class of organic-inorganic extended hybrids and exhibit an open framework structural motif with three-dimensional connectivity of the metal oxygen polyhedra and one-dimensional channels along the c axis. The channels are decorated with the trifluoromethyl groups of the trifluoroacetate ligands, and their average (minimum) diameters are ~3.75 (2.60) and 3.45 (2.25) A for Sr(CF3COO)2 and Ba(CF3COO)2, respectively. This size range is comparable to the kinetic diameter of small molecules such as hydrogen (2.3 A). Chemical substitution of barium for strontium affects not only the diameter of the channels but also the spatial arrangement of the trifluoromethyl groups within the channels and the coordination environment of the metal atoms. The different coordination requirements of the strontium and barium atoms are accommodated through the displacement of one of the two chemically distinct trifluoroacetate ligands relative to the metal center. PMID- 26673003 TI - Efficacy of Dasatinib in a CML Patient in Blast Crisis with F317L Mutation: A Case Report and Literature Review. AB - The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has significantly increased survival rate and quality of life for patients with CML. Despite the high efficacy of imatinib, not all patients benefit from this treatment. Resistance to imatinib can develop from a number of mechanisms. One of the main reasons for treatment failure is a mutation in the BCR-ABL gene, which leads to therapy resistance and clonal evolution. Clearly, new treatment approaches are required for patients who are resistant to imatinib. However, mutated clones are usually susceptible to second-generation TKIs, such as nilotinib and dasatinib. The choice of the therapy depends on the type of mutation. A large trial program showed that dasatinib is effective in patients previously exposed to imatinib. However, for a minority of patients who experience treatment failure with TKI or progress to advanced-phase disease, allogeneic stem cell transplantation (allo-SCT) remains the therapeutic option. In spite of the high curative potential of allo-SCT, its high relapse rate still requires a feasible strategy of posttransplant treatment and prophylaxis. We report a case of a CML patient with primary resistance to first-line TKI therapy. The patient developed an undifferentiated blast crisis. Before dasatinib therapy, the patient was found to have an F317L mutation. He was successfully treated with dasatinib followed by allo-SCT. In the posttransplant period, preemptive dasatinib treatment was used to prevent disease relapse. PMID- 26673004 TI - Behavioral Cardiovascular Risk Factors - Effect of Physical Activity and Cardiorespiratory Fitness on Cardiovascular Outcomes. AB - Primary and primordial prevention of cardiovascular disease (CVD) requires not only identification of risk factors, but also appropriate and timely therapy. In order to prevent the expected increase in prevalence of CVD, it is essential that clinicians are aware of behavioral cardiovascular risk factors. A basic review is critical to clarify the difference between physical activity and fitness, as well as to discuss the role each plays in cardiovascular outcomes. We discuss observational epidemiological studies and randomized control trials that have examined the effect of physical activity and cardiorespiratory fitness on CVD. PMID- 26673005 TI - Ultrasound assessment of thrombotic complications in pediatric patients with tunneled central venous catheters. AB - Central venous access consists in inserting a vascular catheter to the vena cava and placing its tip in the vicinity of the opening to the right atrium. In the patients of the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdansk, such implantation procedures are conducted 40-50 times in a year using Broviac/Hickman catheters that are placed in the subclavian vein. In the Ultrasound and Biopsy Laboratory at the clinic mentioned above, approximately 200-250 examinations have been conducted since 2005 to assess the central venous access. Implantation of a catheter considerably increases the comfort of patients who require a long-term venous access. Nevertheless, it is an invasive procedure, burdened with a risk of numerous, early and late complications. The late complications are associated with implanted catheters and include catheter-related thrombosis. The aim of this paper was to present three patients of the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdansk, in whom thrombotic complications occurred as a result of long-term central venous catheters. The paper also discusses the possibilities of using sonography in the assessment of such complications. In the presented patients, it was possible to determine the size and localization of a thrombus which enabled effective treatment in two cases. The pathomechanism of catheter-related thrombosis was explained and the risk factors of such complications were discussed. The attention was paid to the necessity of conducting ultrasound examinations in pediatric patients with inserted catheters as soon as the first symptoms of thrombosis appear. Based on own observations and despite the lack of validation of ultrasound imaging in the assessment of central catheters, we believe that this method is highly promising and can be recommended for the assessment of thrombotic complications in pediatric patients with central venous catheters. PMID- 26673006 TI - Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells. AB - PURPOSE: Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. RESULTS: The combination of metformin with MEK-I showed a strong anti proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters. CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9. PMID- 26673008 TI - FGFR1 is an adverse outcome indicator for luminal A breast cancers. AB - Fibroblast growth factor receptor 1 (FGFR1) has been suggested to be the candidate gene for 8p11-12 amplification in breast cancer and its therapeutic/ prognostic value is explored. Most previous studies focused on FGFR1 gene amplification, which may not necessarily lead to protein expression. Therefore, analysis of protein level may have more clinical relevance. We evaluated FGFR1 expression in a large cohort of breast cancer by immunohistochemistry, correlated with the tumor clinic-pathologic features, biomarkers expression, and patient's survival. FGFR1 expression was associated mainly with luminal cancers, particularly luminal B subtype (23.5%; p < 0.001), and it also showed adverse prognostic impact on luminal A cancers. FGFR1 expression was associated with higher pN (p = 0.023), pT (p = 0.003) stages, lymphovascular invasion (p = 0.010), p-cadherin (p = 0.028), synaptophysin (p = 0.009) and SOX2 expression (p = 0.034) in luminal A cancers. FGFR1 expressing luminal A cancers showed a similar outcome as luminal B cancers. Multivariate Cox regression analysis demonstrated FGFR1 positive luminal A cancers to be an independently poor prognosticator for disease free survival in luminal cancers (hazard ratio = 3.341, p = 0.008). Thus FGFR1 could be useful in identifying the aggressive cases amongst heterogeneous luminal A cancers. Given the relevance of FGFR pathway in treatment resistance in luminal cancers, FGFR1 could be an important tumor biomarker and adverse prognostic factor potentially exploitable in the clinical management of luminal cancers. PMID- 26673011 TI - Kinetics of Oxygen Surface Exchange on Epitaxial Ruddlesden-Popper Phases and Correlations to First-Principles Descriptors. AB - Through alignment of theoretical modeling with experimental measurements of oxygen surface exchange kinetics on (001)-oriented La2-xSrxMO4+delta (M = Co, Ni, Cu) thin films, we demonstrate here the capability of the theoretical bulk O 2p band centers to correlate with oxygen surface-exchange kinetics of the Ruddlesden Popper oxide (RP214) (001)-oriented thin films. In addition, we demonstrate that the bulk O 2p-band centers can also correlate with the experimental activation energies for bulk oxygen transport and oxygen surface exchange of both the RP214 and the perovskite polycrystalline materials reported in the literature, indicating the effectiveness of the bulk O 2p-band centers in describing the associated energetics and kinetics. We propose that the opposite slopes of the bulk O 2p-band center correlations between the RP214 and the perovskite materials are due to the intrinsic mechanistic differences of their oxygen surface exchange kinetics and bulk anionic transport. PMID- 26673009 TI - Sphingosine kinase 1 is overexpressed and promotes adrenocortical carcinoma progression. AB - Adrenocortical carcinoma (ACC) is a rare endocrine tumor with a very poor prognosis. Sphingosine kinase 1 (SphK1), an oncogenic kinase, has previously been found to be upregulated in various cancers. However, the role of the SphK1 in ACC has not been investigated. In this study, SphK1 mRNA and protein expression levels as well as clinicopathological significance were evaluated in ACC samples. In vitro siRNA knockdown of SphK1 in two ACC cell lines (H295R and SW13) was used to determine its effect on cellular proliferation and invasion. In addition, we further evaluated the effect of SphK1 antagonist fingolimod (FTY720) in ACC in vitro and in vivo, as a single agent or in combination with mitotane, and attempted to explore its anticarcinogenic mechanisms. Our results show a significant over-expression of SphK1 mRNA and protein expression in the carcinomas compared with adenomas (P < 0.01 for all comparisons). Functionally, knockdown of SphK1 gene expression in ACC cell lines significantly decreased cell proliferation and invasion. FTY720 could result in a decreased cell proliferation and induction of apoptosis, and the combination of mitotane and FTY720 resulted in a greater anti-proliferative effect over single agent treatment in SW13 cells. Furthermore, FTY720 could markedly inhibit tumor growth in ACC xenografts. SphK1 expression is functionally associated to cellular proliferation, apoptosis, invasion and mitotane sensitivity of ACC. Our data suggest that SphK1 might be a potential therapeutic target for the treatment of ACC. PMID- 26673007 TI - Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells. AB - Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notch signaling pathway. Quinomycin treatment resulted in significant inhibition of proliferation and colony formation in pancreatic cancer cell lines, but not in normal pancreatic epithelial cells. Moreover, Quinomycin affected pancreatosphere formation. The compound also decreased the expression of CSC marker proteins DCLK1, CD44, CD24 and EPCAM. In addition, flow cytometry studies demonstrated that Quinomycin reduced the number of DCLK1+ cells. Furthermore, levels of Notch 1-4 receptors, their ligands Jagged1, Jagged2, DLL1, DLL3, DLL4 and the downstream target protein Hes-1 were reduced. The gamma-secretase complex proteins, Presenilin 1, Nicastrin, Pen2, and APH-1, required for Notch activation also exhibited decreased expression. Ectopic expression of the Notch Intracellular Domain (NICD) partially rescued the cells from Quinomycin mediated growth suppression. To determine the effect of Quinomycin on tumor growth in vivo, nude mice carrying tumor xenografts were administered Quinomycin intraperitoneally every day for 21 days. Treatment with the compound significantly inhibited tumor xenograft growth, coupled with significant reduction in the expression of CSC markers and Notch signaling proteins. Together, these data suggest that Quinomycin is a potent inhibitor of pancreatic cancer that targets the stem cells by inhibiting Notch signaling proteins. PMID- 26673012 TI - Zinc-Containing Magnetic Oxides Stabilized by a Polymer: One Phase or Two? AB - Here we developed a new family of Zn-containing magnetic oxides of different structures by thermal decomposition of Zn(acac)2 in the reaction solution of preformed magnetite nanoparticles (NPs) stabilized by polyphenylquinoxaline. Upon an increase of the Zn(acac)2 loading from 0.15 to 0.40 mmol (vs 1 mmol of Fe(acac)3), the Zn content increases, and the Zn-containing magnetic oxide NPs preserve a spinel structure of magnetite and an initial, predominantly multicore NP morphology. X-ray photoelectron spectroscopy (XPS) of these samples revealed that the surface of iron oxide NPs is enriched with Zn, although Zn species were also found deep under the iron oxide NP surface. For all the samples, XPS also demonstrates the atom ratio of Fe(3+)/Fe(2+) = 2:1, perfectly matching Fe3O4, but not ZnFe2O4, where Fe(2+) ions are replaced with Zn(2+). The combination of XPS with other physicochemical methods allowed us to propose that ZnO forms an ultrathin amorphous layer on the surface of iron oxide NPs and also diffuses inside the magnetite crystals. At higher Zn(acac)2 loading, cubic ZnO nanocrystals coexist with magnetite NPs, indicating a homogeneous nucleation of the former. The catalytic testing in syngas conversion to methanol demonstrated outstanding catalytic properties of Zn-containing magnetic oxides, whose activities are dependent on the Zn loading. Repeat experiments carried out with the best catalyst after magnetic separation showed remarkable catalyst stability even after five consecutive catalytic runs. PMID- 26673010 TI - Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors. AB - PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. EXPERIMENTAL DESIGN: We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. RESULTS: sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. CONCLUSIONS: sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs. PMID- 26673013 TI - Light-Induced In Situ Transformation of Metal Clusters to Metal Nanocrystals for Photocatalysis. AB - In situ transformation of glutathione-capped gold (Aux) clusters to gold (Au) nanocrystals under simulated solar light irradiation was achieved and utilized as a facile synthetic approach to rationally fabricate Aux/Au/TiO2 ternary and Au/TiO2 binary heterostructures. Synergistic interaction of Aux clusters and Au nanocrystals contributes to enhanced visible-light-driven photocatalysis. PMID- 26673014 TI - Friendship Security, But Not Friendship Intimacy, Moderates the Stability of Anxiety During Preadolescence. AB - A two-wave longitudinal study of 380 preadolescents (M age = 10.87) from largely middle-class schools in Montreal, Quebec, Canada, assessed the hypothesis that friendship security, but not friendship intimacy, moderates the stability of anxiety during adolescence. This central but largely overlooked question about peer relations concerns which aspects of friendship account for the effects of friendship on emotional adjustment. Anxiety and friendship quality were measured via self-report questionnaires, employing the Network of Relationships Inventory for security and intimacy items. An index of friendship durability, which combined reciprocity and stability within first- and second-best friendship choices, was derived from sociometric measures. A latent variable path analysis examined with structural equation modeling showed that anxiety was less stable for children who perceived their friendships as secure. The moderating effect of intimacy was statistically nonsignificant. A follow-up analysis showed that the effects of security did not result from friendship durability. These findings provide support for the long-standing but previously unaddressed hypothesis that security, rather than intimacy, accounts for friendship's effect on anxiety reduction during early adolescence. PMID- 26673015 TI - Isolation of Nicotinic Acid (Vitamin B3) and N-Propylamine after Myosmine Peroxidation. AB - The alkaloid myosmine (3-(1-pyrroline-2-yl)pyridine) is widespread in biological matrixes including foodstuffs and tobacco products. Some in vitro tests in cellular systems showed mutagenic activity for myosmine. Myosmine activation including peroxidation mechanism employs unstable oxazirane intermediates. The formation of minor metabolite 3-hydroxymethyl-pyridine in rat metabolism experiments as well as in in vitro peroxidation assays suggests its further oxidation to nicotinic acid and possible concomitant formation of n-propylamine. A sensitive high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed for the direct analysis of n-propylamine in the peroxidation assay solution of myosmine employing derivatization with 3,5-dinitrobenzoyl chloride. Additionally, during peroxidation procedures, formation of 3-pyridylmethanol to nicotinic acid, the essential vitamin B3, was observed and characterized using HPLC-UV and gas chromatography/mass spectrometry. This new reaction pathway may present further contribution to our knowledge of myosmine's significance in human food including its activation in human organism, foodstuffs, and biological systems. PMID- 26673016 TI - Non Surgical Correction of Mandibular Deviation and Neuromuscular Coordination after Two years of Mandibular Guidance Therapy: A Case Report. AB - Carcinomas of the mandible may require resection of a segment of bone (continuity defect), partial removal of bone (discontinuity defect), tongue, and floor of the mouth and muscle attachments. Patients undergoing such treatment suffer from facial disfigurement, loss of muscle function, loss of neuromuscular coordination resulting in inability to masticate and swallow acceptably. Surgical reconstruction may not always be possible because of high reoccurrence rate, inability of the patient to cope with another surgery etc. The treatment of choice in non surgical cases is prosthetic rehabilitation using guiding flange prosthesis. This article describes the management of a patient who had undergone hemimandibulectomy and was not willing for a surgical reconstruction. Interim maxillary ramp prosthesis was given to the patient 15 days postoperatively followed by definitive guiding flange prosthesis for two years after which the patient was able to occlude in centric occlusal position without any aid. PMID- 26673017 TI - Nonpathological Lesser Trochanter Fracture in Adult: Case Report and Brief Review of Literature. AB - Lesser trochanter fractures are rare in adult bones. Few cases have been reported in the literature. When fracture of lesser trochanter is met in patients with closed growth plates, it is likely to be precursor of a silent neoplastic process. A case of lesser trochanter fracture in middle aged female with traumatic aetiology is presented here, which came out to be non-pathological despite high degree of suspicion for contrary. Patient responded positively to conservative line of treatment. Correct evaluation and anticipation of further complication take precedence in case rather than rarity. PMID- 26673018 TI - Association between circulating CCL2 levels and modifiable behaviors in overweight and obese adolescents: a cross-sectional pilot study. AB - BACKGROUND: We evaluated the relationship between an early inflammatory biomarker, chemokine (C-C motif) ligand 2 (CCL2), and other clinical biomarkers and lifestyle behaviors, in overweight/obese adolescents at high risk of developing cardiometabolic derangements. METHODS: We collected anthropometric measurements, clinical biomarkers, and three 24-h dietary recalls from 21 vocational high school students (91% male), 14-19 years, with body mass index (BMI) >=25 kg/m2. Pearson's or Spearman's correlation coefficients were used to examine relationships. RESULTS: Mean BMI was 33.2 kg/m2 (range 25.7-45.6) and 38% were prediabetic by fasting glucose. Mean CCL2 was 512.9 pg/mL (range 220-917) and positively correlated with triglycerides (r=0.45; p=0.04) and TNF-alpha (r=0.57; p=0.007) and marginally negatively correlated with fruit/vegetable intake (r=-0.42, p=0.06) and omega-3 fatty acids (r=-0.41, p=0.07). CONCLUSIONS: CCL2 was positively associated with pro-inflammatory biomarkers and negatively associated with some anti-inflammatory dietary factors. PMID- 26673019 TI - Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys. AB - BACKGROUND: We aimed to assess the association between exposure to sunshine during gestation and the risk of type 1 diabetes (T1D) in Danish children. METHODS: The study population included 331,623 individuals born in Denmark from 1983 to 1988; 886 (0.26%) developed T1D by the age of 15 years. The values of sunshine hours were obtained from the Danish Meteorological Institute. Gestational exposure to sunshine was calculated by summing recorded monthly sunshine hours during the full 9 months prior to the month of birth. The linear variable then was split into two categories separated by the median value. RESULTS AND CONCLUSIONS: Cox regression models showed that more sunshine during the third gestational trimester was associated with lower hazards (HR) of T1D at age 5-9 years in males: HR (95% CI): 0.60 (0.43-0.84), p=0.003. Our results should be considered in the context of evidence-based recommendations to the public about skin protection from the sun. PMID- 26673020 TI - The CLU-files: disentanglement of a mystery. AB - The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory clusterin (sCLU), also known as apolipoprotein J (apoJ), is considered one of the most important extracellular chaperones ever found. It is involved in a broad range of physiological and pathophysiological functions, where it exerts a cytoprotective role. Descriptions of various forms of intracellular CLU have led to further and even contradictory functions. To untangle the current state of knowledge of CLU, this review will combine old views in the field, with new discoveries to highlight the nature and function of this fascinating protein(s). In this review, we further describe the expression and subcellular location of various CLU forms. Moreover, we discuss recent insights into the structure of CLU and assess how structural properties as well as the redox environment determine the chaperone activity of CLU. Eventually, the review connects the biochemistry and molecular cell biology of CLU with medical aspects, to formulate a hypothesis of a CLU function in health and disease. PMID- 26673021 TI - Nature Index 2015 China. PMID- 26673022 TI - Building a powerhouse. PMID- 26673023 TI - The rapid rise of a research nation. PMID- 26673024 TI - Three giants tighten their grip. PMID- 26673025 TI - At the very heart of progress. PMID- 26673026 TI - The changing face of industry. PMID- 26673027 TI - Alliances for scientific success. PMID- 26673028 TI - A guide to the Nature Index. PMID- 26673030 TI - Drug Audit of Intravenous Anaesthetic Agents in Tertiary Care Hospital. AB - INTRODUCTION: Drug cost is essential component of anaesthesia pharmacoeconomics. Recently pharmacoeconomics has emerged to measure, compare and evaluate cost of drug therapy to health system and decide which strategies produce best outcomes for resources allocated. The present study was planned to find utilization of intravenous anaesthetic agents in a tertiary care hospital and to find the pharmacoeconomics related to utilized and un-utilized drug data. MATERIALS AND METHODS: Prospective observational study was conducted for 3 months and 200 cases were recorded undergoing surgical procedures under general anaesthesia only. Intravenous drugs were considered excluding inhalational anaesthetics. Data for drug utilized and un-utilized was collected. Cost estimation was done. RESULTS: Thiopentone sodium was frequently used intravenous inducing anaesthetic agent in 75% of patients. On average 6.5 drugs were prescribed per patient as pre anaesthetic and intravenous inducing anaesthetic medications. 100% of drugs were prescribed by generic name, 92.30% were from National Essential Drug List. Amongst intravenous anaesthetic agents maximum wastage was associated with propofol of about 36.59% and in pre-anaesthetics, wastage was maximum for atropine 79% followed by glycopyrrolate 45.95%, pentazocine 45.95%. The cost of wasted drugs for study duration was 29.82% (Rs. 10,276.25) of the total cost of drugs was loaded (Rs.34458.84). Of this, the cost of wastage of vecuronium was maximum being 16.82% (Rs.1728) of the total cost wastage, followed by rocuronium 15.38% (Rs.1580.80), glycopyrrolate 15.22% (Rs.1564), and neostigmine 10.95% (Rs.1125.12). The cost of wasted drug per case was maximum for rocuronium being Rs.158.08 and least for ketamine Rs. 1.18. CONCLUSION: There is need to formulate indicators for intravenous anaesthetic agents utilization. The most commonly prescribed drug glycopyrrolate is still not in National Essential Drug List. The judicious use of these drugs and appropriate measures can effectively decrease the cost in terms of un-utilized drugs. PMID- 26673031 TI - End-of-Life Cancer Care: Temporal Association between Homecare Nursing and Hospitalizations. AB - OBJECTIVES: Most cancer patients want to die at home, but scaleable models to achieve this are not well researched. Our objective was to investigate the temporal association of homecare nursing, especially by generalist nurses, with reduced end-of-life hospitalizations. METHODS: We conducted a retrospective Canadian cohort study of end-of-life cancer decedents during 2004-2009 in Ontario (ON), Nova Scotia (NS), and British Columbia (BC), which have homecare systems that use generalist nurses to provide end-of-life care. Each province linked administrative databases to examine the association during the last six months of life between the homecare nursing rate and the hospitalization rate in the subsequent week, using standardized definitions and controlling for other covariates. We dichotomized nursing into standard and end-of-life care intent. RESULTS: Our cohort included 83,827 cancer decedents. Approximately 55% of decedents were older than 70 and the most common cancer was lung. Nearly 85% of the cohort had at least one hospital admission. Receiving end-of-life compared to standard homecare nursing significantly reduced a patient's hospitalization rate by 34%, 33%, and 17% in ON, BC, and NS. In the last month of life patients having a standard nursing rate of greater than five hours compared to one hour per week had a significantly lower hospitalization rate (relative reduction of 15%-23%) across the three provinces. CONCLUSIONS: Our study showed a protective effect of nursing with an end-of-life intent on hospitalization across the last six months of life and of standard nursing in the last month. This finding's generalizability is strengthened, since the trends were similar across three different homecare systems. PMID- 26673032 TI - Hierarchical Nanowire Arrays as Three-Dimensional Fractal Nanobiointerfaces for High Efficient Capture of Cancer Cells. AB - A hierarchical assembled ITO nanowire array with both horizontal and vertical nanowire branches was fabricated as a new three-dimensional fractal nanobiointerface for efficient cancer cell capture. Comparing with ITO nanowire array without branches, this fractal nanobiointerface exhibited much higher efficiency (89% vs 67%) and specificity in capturing cancer cells and took shorter time (35 vs 45 min) to reach the maximal capture efficiency. As indicated by the immunofluorescent and ESEM images, this enhancement can be attributed to the improvement of topographical interaction between cells and the substrate. The introduction of horizontal and vertical nanowire branches makes the substrate topographically match better with cell filopodia and provides more binding sites for cell capture. The live/dead cell staining and proliferation experiments confirm that this fractal nanobiointerface displays excellent cyto-compatibility with an over 96% cell viability after capture. These results provide new insights and may open up opportunities in designing and engineering new cell-material interfaces for advanced biomedical applications. PMID- 26673033 TI - Comparison of endoscopic submucosal dissection and surgical resection for treating gastric subepithelial tumours. AB - OBJECTIVE: For subepithelial tumours (SETs) of the stomach, surgical resection is the gold standard treatment. With the recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative treatment for SETs. The aim of our study was to evaluate the clinical outcomes of ESD for treating gastric SETs compared with surgical resection. METHODS: Between January 2006 and September 2014, 55 patients with gastric SETs (13 gastrointestinal stromal tumours (GISTs), 27 leiomyomas, and 15 others) were treated by ESD and 27 patients (19 GISTs, two leiomyomas, and six others) underwent surgical resection. We retrospectively reviewed the therapeutic outcomes, procedure-related complications, post-procedure hospital stays, and medical costs of the two groups. RESULTS: The complete resection rate of the ESD group was lower than that of the surgery group (81.8% vs. 100%, p = 0.026). Although the incidence of complications that occurred with ESD was higher than that associated with surgical resection, there were no significant between group differences (12.5% vs. 3.7%, p = 0.261), and all complicated cases were successfully treated without mortality. The ESD group had significantly shorter post-procedural hospital stays (median five days vs. eight days, p = 0.034) and lower medical costs (median $2374 vs. $4954, p <0.001) than the surgery group. There were no recurrences in either group during the follow-up period. CONCLUSIONS: ESD is an efficient treatment tool for gastric SETs in selected patients. Additionally, ESD has the advantages of shorter hospital stays and lower medical costs compared with surgery. PMID- 26673034 TI - Hip Range of Motion Is Lower in Professional Soccer Players With Hip and Groin Symptoms or Previous Injuries, Independent of Cam Deformities. AB - BACKGROUND: Soccer (football) players often have hip and groin symptoms (HGS), and a previous groin injury is a risk factor for a relapse. Decreased hip range of motion (HROM) has been related to both hip and groin pain and the presence of a cam deformity. How these factors interact is unknown. PURPOSE: The first aim was to study whether HGS are associated with HROM. The second aim was to study the association of the presence of a cam deformity with HROM. Additionally, the influence of a cam deformity on the relationship between HGS and HROM was examined. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Seasonal screening data of 2 professional soccer clubs were used. Variables for HGS were current hip or groin pain, the Copenhagen Hip and Groin Outcome Score (HAGOS), and previous hip- and groin-related time-loss injuries (HGTIs). HROM was determined for hip internal rotation (IR), external rotation, and total rotation (TR) in the supine position and for the bent knee fall out (BKFO) test. A cam deformity was defined by an alpha angle >60 degrees on standardized anteroposterior pelvic and frog-leg lateral radiographs. RESULTS: Sixty players (mean [+/-SD] age, 23.1 +/- 4.2 years) were included. All were noninjured at the time of screening. Current hip or groin pain was not associated with HROM. Hips of players in the lowest HAGOS interquartile range (thus most affected by complaints; n = 12) showed less IR (23.9 degrees +/- 8.7 degrees vs 28.9 degrees +/- 7.8 degrees , respectively; P = .036) and TR (58.2 degrees +/- 13.5 degrees vs 65.6 degrees +/- 11.8 degrees , respectively; P = .047) than those in the highest interquartile range (n = 29). No such differences were found for BKFO (P = .417). Hips of players with a previous HGTI showed less IR (21.1 degrees +/- 6.8 degrees vs 28.3 degrees +/- 8.9 degrees , respectively; P < .001) and TR (56.0 degrees +/- 8.2 degrees vs 64.5 degrees +/- 13.6 degrees , respectively; P < .001) than those without a previous HGTI. This was independent of the presence of a cam deformity. BKFO did not differ between groups (P = .983). Hips with a cam deformity showed less but nonsignificant IR (25.5 degrees +/- 10.3 degrees vs 29.0 degrees +/- 7.1 degrees , respectively; P = .066) and TR (P = .062) and higher but nonsignificant BKFO values (17.1 cm +/- 3.4 cm vs 14.2 cm +/- 4.6 cm, respectively; P = .078) than those without a cam deformity. CONCLUSION: Decreased HROM in professional soccer players is associated with more hip- and groin-related symptoms and with previous injuries, independent of the presence of a cam deformity. PMID- 26673035 TI - The Efficacy of Injury Prevention Programs in Adolescent Team Sports: A Meta analysis. AB - BACKGROUND: Intensive sport participation in childhood and adolescence is an established cause of acute and overuse injury. Interventions and programs designed to prevent such injuries are important in reducing individual and societal costs associated with treatment and recovery. Likewise, they help to maintain the accrual of positive outcomes from participation, such as cardiovascular health and skill development. To date, several studies have individually tested the effectiveness of injury prevention programs (IPPs). PURPOSE: To determine the overall efficacy of structured multifaceted IPPs containing a combination of warm-up, neuromuscular strength, or proprioception training, targeting injury reduction rates according to risk exposure time in adolescent team sport contexts. STUDY DESIGN: Systematic review and meta analysis. METHODS: With established inclusion criteria, studies were searched in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, SPORTDiscus, Web of Science, EMBASE, CINAHL, and AusSportMed. The keyword search terms (including derivations) included the following: adolescents, sports, athletic injuries, prevention/warm-up programs. Eligible studies were then pooled for meta-analysis with an invariance random-effects model, with injury rate ratio (IRR) as the primary outcome. Heterogeneity among studies and publication bias were tested, and subgroup analysis examined heterogeneity sources. RESULTS: Across 10 studies, including 9 randomized controlled trials, a pooled overall point estimate yielded an IRR of 0.60 (95% CI = 0.48-0.75; a 40% reduction) while accounting for hours of risk exposure. Publication bias assessment suggested an 8% reduction in the estimate (IRR = 0.68, 95% CI = 0.54-0.84), and the prediction interval intimated that any study estimate could still fall between 0.33 and 1.48. Subgroup analyses identified no significant moderators, although possible influences may have been masked because of data constraints. CONCLUSION: Compared with normative practices or control, IPPs significantly reduced IRRs in adolescent team sport contexts. The underlying explanations for IPP efficacy remain to be accurately identified, although they potentially relate to IPP content and improvements in muscular strength, proprioceptive balance, and flexibility. CLINICAL RELEVANCE: Clinical practitioners (eg, orthopaedics, physical therapists) and sports practitioners (eg, strength and conditioners, coaches) can respectively recommend and implement IPPs similar to those examined to help reduce injury rates in adolescent team sports contexts. PMID- 26673036 TI - Synthesis of a Gemcitabine Prodrug for Remote Loading into Liposomes and Improved Therapeutic Effect. AB - The chemotherapeutic gemcitabine was actively and stably loaded into lipid nanoparticles through the formation of a prodrug. Gemcitabine was chemically modified to increase the lipophilicity and introduce a weak base moiety for remote loading. Several derivatives were synthesized and screened for their potential to be good liposomal drug candidates for remote loading by studying their solubility, stability, cytotoxicity, and loading efficiency. Two morpholino derivatives of GEM (22 and 23) were chosen as the preferred prodrugs for this purpose as they possessed the best loading efficiencies (100% for drug-to-lipid ratio of 0.36 w/w). This is a considerable improvement over a passive loading strategy where typical loading efficiencies are on the order of ~10-20% for a drug-to-lipid ratio of ~0.01. Liposomes loaded with these two prodrugs were studied in an s.c. tumor model in vivo and showed improved therapeutic effect over free GEM (~2-fold) and saline control (8- to 10-fold). This work demonstrates how chemical modification of a known hydrophilic drug can lead to improved loading, stability, and drug delivery in vivo. PMID- 26673037 TI - Surgical and Functional Outcomes in Patients Undergoing Total Knee Replacement With Patient-Specific Implants Compared With "Off-the-Shelf" Implants. AB - BACKGROUND: Total knee arthroplasty (TKA) instrumentation and implant designs have been evolving, with one of the current innovations being patient-specific implants (PSIs). PURPOSE: To evaluate whether there is a significant difference in surgical time, intraoperative blood loss, postoperative range of motion, and length of stay between PSI and conventional TKA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A consecutive series of 621 TKA patients, 307 with PSIs and 314 with conventional implants, was reviewed. Differences in estimated blood loss, length of stay, range of motion, and surgical time/tourniquet time between the 2 cohorts were analyzed. RESULTS: Linear regression analysis demonstrated that PSI decreased estimated blood loss by 44.72 mL (P < .01), decreased length of stay by 0.39 days (P < .01), decreased postoperative range of motion by 3.90 degrees (P < .01), and had a negligible difference on surgical and tourniquet time. CONCLUSION: The use of PSI is associated with decreased estimated blood loss, decreased length of stay, decreased range of motion, and no discernible difference in surgical or tourniquet time, all of which are unlikely to be clinically significant. PMID- 26673038 TI - N-Calpha Bond Cleavage of Zinc-Polyhistidine Complexes in Electron Transfer Dissociation Mediated by Zwitterion Formation: Experimental Evidence and Theoretical Analysis of the Utah-Washington Model. AB - Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of gas-phase ions are widely used for peptide/protein sequencing by mass spectrometry. To understand the general mechanism of ECD/ETD of peptides, we focused on the ETD fragmentation of metal-peptide complexes in the absence of remote protons. Since Zn(2+) strongly binds to neutral histidine residues in peptides, Zn(2+)-polyhistidine complexation does not generate any remote protons. However, in the absence of remote protons, electron transfer to the Zn(2+) polyhistidine complex induced the N-Calpha bond cleavage. The formation pathway for the ETD products was investigated by density functional theory calculations. The calculations showed that the charge-reduced zinc-peptide radical, [M + Zn](*+), can exist in the low-energy zwitterionic amide pi* states, which underwent homolytic N-Calpha bond dissociation. The homolytic cleavage resulted in the donation of an electron from the N-Calpha bond to the nitrogen atom, producing an iminoenol c' anion. The counterpart z(*) radical contained a radical site on the alpha-carbon atom. The iminoenol c' anion then abstracted a proton to presumably form the more stable amide c' fragment. The current experimental and computational joint study strongly suggested that the N-Calpha bond cleavage occurred through the aminoketyl radical-anion formation for Zn(2+)-polyhistidine complexes in ETD. PMID- 26673039 TI - Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. AB - AIM: DNA methylation is the best known epigenetic mark. Cancer and other pathologies show an altered DNA methylome. However, delivering complete DNA methylation maps is compromised by the price and labor-intensive interpretation of single nucleotide methods. MATERIAL & METHODS: Following the success of the HumanMethylation450 BeadChip (Infinium) methylation microarray (450K), we report the technical and biological validation of the newly developed MethylationEPIC BeadChip (Infinium) microarray that covers over 850,000 CpG methylation sites (850K). The 850K microarray contains >90% of the 450K sites, but adds 333,265 CpGs located in enhancer regions identified by the ENCODE and FANTOM5 projects. RESULTS & CONCLUSION: The 850K array demonstrates high reproducibility at the 450K CpG sites, is consistent among technical replicates, is reliable in the matched study of fresh frozen versus formalin-fixed paraffin-embeded samples and is also useful for 5-hydroxymethylcytosine. These results highlight the value of the MethylationEPIC BeadChip as a useful tool for the analysis of the DNA methylation profile of the human genome. PMID- 26673040 TI - Impact of volume expansion on the efficacy and pharmacokinetics of liposome bupivacaine. AB - Liposome bupivacaine is a prolonged-release liposomal formulation of bupivacaine indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia of longer duration than traditional local anesthetics. This review summarizes the available data on how volume expansion may impact the analgesic efficacy of liposome bupivacaine. The Phase II and III clinical studies that involved surgical site administration of liposome bupivacaine at various concentrations in different surgical settings revealed no apparent concentration efficacy relationship. A single-center, prospective study comparing the efficacy of transversus abdominis plane infiltration with liposome bupivacaine administered in a lower (266 mg/40 mL) vs a higher (266 mg/20 mL) dose concentration in subjects undergoing robotic-assisted laparoscopic prostatectomy also reported similar postsurgical pain intensity scores and opioid usage in both treatment groups. The pharmacokinetic profile of liposome bupivacaine following subcutaneous injections in rats was unaltered by differences in drug concentration, dose, or injection volume within the ranges tested. Volume expansion of liposome bupivacaine to a total volume of 300 mL or less does not appear to impact its clinical efficacy or pharmacokinetic profile, thus allowing flexibility to administer the formulation across a wide range of diluent volumes. PMID- 26673041 TI - Reduction of the ages at diagnosis and operation of biliary atresia in Taiwan: A 15-year population-based cohort study. AB - AIM: To describe the ages at diagnosis and operation of biliary atresia (BA) and its incidence over a 15-year period in Taiwan. METHODS: This was a population based cohort study. BA cases were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases, Ninth Revision (ICD-9) code of BA 751.61 plus Kasai operation (ICD-9 procedure code 51.37) or liver transplantation (LT, ICD-9 procedure code 50.5). The patients' characteristics including sex, age at diagnosis, age at receiving Kasai operation and age at receiving LT were compared among three birth cohorts: (1) 1997 to 2001; (2) 2002 to 2006; and (3) 2007 to 2011. RESULTS: There were a total of 540 BA cases (275 females) with an incidence of 1.62 per 10000 live births. No seasonality of BA was noted. The mean ages at diagnosis of three cohorts were 57.9, 55.6 and 52.6 d. A linear regression model demonstrated a decreasing trend of the mean age at diagnosis (1.27 d per year). The proportion of BA cases that received the Kasai operation within 60 d of age increased from 76% to 81%. A total of 189 (35%) BA patients underwent LT. The mean age at LT was reduced from 3-year-old to 1-year-old. The rates of LT were 25.6% and 32.3% in patients who received the Kasai operation within 60 d or after 60 d of age, respectively. All patients who did not undergo a Kasai operation eventually required LT. CONCLUSION: The ages at diagnosis and operation in BA cases have decreased over time. Kasai operation performed at younger age reduces the need for LT. The incidence of BA in Taiwan fluctuates, but without certain trend. PMID- 26673042 TI - Prevalence of Complications and Clinical Audit of Management of Type 2 Diabetes Mellitus: A Prospective Hospital Based Study. AB - INTRODUCTION: Management of type 2 diabetes mellitus (DM) needs multi factorial risk reduction strategies like weight reduction, blood pressure (BP) control and lipid profile regulation, along with glycaemic control. These strategies should be implemented very early in the course of the disease to prevent both microvascular and macro vascular complications. AIM: To find out the prevalence of diabetic complications and to audit the management of glycaemia, blood pressure and serum lipids in the outpatient diabetes clinic in a hospital located in Western U.P. MATERIALS AND METHODS: A prospective study conducted in a tertiary referral teaching hospital, on 105 patients with type 2 diabetes mellitus (mean age 52.84 +/- 1.02 years) who attended the diabetic clinic during June 2014 to April 2015, who had undergone screening for complications. MAIN OUTCOME MEASURES: Weight, height, body mass index (BMI), blood pressure, fasting and post prandial blood sugars, glycated hemoglobin, serum lipids and presence of diabetic microvascular as well as macrovascular complications. Mean of various clinical and biochemical parameters were compared in patients with and without complications. RESULTS: The mean age of patients was estimated as 52.84 +/- 1.02 years. Fifty six percent of patients were males. Average BMI was 28.61 +/- 0.28 kg/m(2). Most of them had abdominal obesity. The average duration of diabetes was 8.39 +/- 0.6 years. The average of systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1C, FBS, PPBS, LDL, HDL and triglyceride were estimated as 129.1 +/- 1.49 mm Hg, 84.85 +/- 0.94 mm Hg, 6.99 +/- 0.08%, 141.33 +/- 2.12 mg/dl, 214.51 +/- 3.11 mg/dl, 155.66 +/- 2.07 mg /dl, 40.07 +/- 0.38 mg/dl, 236.53 +/- 3.31 mg/dl respectively based on 105 patients. Amongst micro vascular complications; retinopathy, neuropathy and nephropathy were documented in 51.4, 77.14 and 30.47% diabetes patients respectively. The prevalence of coronary artery disease, stroke and gangrene were 42.85, 12.38 and 3.80% respectively. CONCLUSION: The prevalence and risk of the complications of type 2 DM significantly increased with age of patients, duration of diabetes, fasting blood sugar and LDL levels. The awareness regarding monitoring of target BP and lipid profile is needed beyond the glycaemic control, amongst patients and health care providers. PMID- 26673044 TI - A technique to visualise the urethral meatus in difficult male catheterisations. PMID- 26673043 TI - Identification and occurrence of endogenous semicarbazide in prawns and crabs from Zhejiang Province, China. AB - Semicarbazide (SEM) is a side-chain metabolite of the antibiotic drug nitrofurazone (NFZ) and is employed as a conclusive marker for the use of banned NFZ. Recent studies have shown that SEM in aquatic crustaceans can be derived natively or from other sources. The presence and distribution of endogenous SEM within aquatic crustaceans is examined in this paper, which finds that the SEM content varies amongst the muscle, shell, and viscera of various prawn and crab species within the range of 0.35-26.62 ng g(-1). The effects of heating and hypochlorite treatment on SEM levels were examined. The results indicate that thermal processing introduced a more significant impact, resulting in a maximum SEM value of 15.48 ng g(-1) in a sample of shell of Portunus trituberculatus crab, while SEM levels in muscle samples were not affected by the duration of heating. Though 6% active chlorine treatment led to SEM production ranging between 39.9 and 196.4 ng g(-1) in muscle samples from various crustaceans, SEM is unlikely to originate from hypochlorite or chlorine in practice where there are limits to actual chlorine in sanitation water and facilities. 5-Nitro-2 furaldehyde (NF) was proposed as a selective marker to differentiate between endogenous SEM and NFZ-derived SEM in seafood. PMID- 26673045 TI - The use of urological hospital services by nonagenarians. AB - INTRODUCTION: The super-elderly population is a small but expanding group of patients who will pose a significant challenge to future healthcare resources. A snapshot audit was completed of all emergency and elective urological nonagenarian activity in a UK general hospital, including surgical outcomes in this group of patients. METHODS: Prospective and retrospective databases and clinical records were examined to identify all patients aged 90-99 years who had patient episodes between January 2006 and August 2012. Patient outcomes were compared with those for a similar cohort of 80-89-year-olds during the same time period. RESULTS: A total of 653 nonagenarian patient episodes were identified (including 138 emergency admissions, 25 emergency surgical procedures, 71 elective surgical procedures, 173 local anaesthetic procedures and 270 outpatient visits). The in-hospital mortality rate for emergency admissions was 10%. The mean length of hospital stay was significantly longer for nonagenarians than for octogenarians (14.4 vs 6.5 days, p<0.00001). The postoperative mortality rate following emergency and elective surgery was 16% and 1% for nonagenarians and octogenarians respectively. CONCLUSIONS: Nonagenarian patients often have complex medical co-morbidities and challenging social circumstances that contribute to delayed recovery from acute illness and surgery as well as long periods of hospitalisation. Adopting a multidisciplinary approach with formal input from specialist geriatric surgical services may improve patient outcomes and allow patients to be discharged to their former places of residence. PMID- 26673046 TI - The three-point landing in mandibular orthognathic surgery--a modified technique. PMID- 26673048 TI - Safe release of gluteus maximus tendon in Kocher-Langenbeck approach for acetabular fracture reconstruction. PMID- 26673047 TI - Impact of a dedicated emergency surgical unit on early laparoscopic cholecystectomy for acute cholecystitis. AB - INTRODUCTION: Emergency general surgery (EGS) accounts for 50% of the surgical workload, and yet outcomes are variable and poorly recorded. The management of acute cholecystitis (AC) at a dedicated emergency surgical unit (ESU) was assessed as a performance target for EGS. METHODS: The outcomes for AC admissions were compared one year before and after inception of the ESU. The impact on cost and compliance with national guidance recommending early laparoscopic cholecystectomy (ELC) within seven days of diagnosis was assessed. RESULTS: The overall ELC rate increased from 26% for the 126 patients admitted in the pre-ESU period to 45% for the 152 patients admitted in the post-ESU period (p=0.001). With those unsuitable for ELC excluded, the ELC rate increased from 34% to 82% (p<0.001). The proportion of patients precluded from ELC for avoidable reasons, particularly owing to 'surgeon preference/skill', was reduced from 69% to 18% (p<0.001). The mean total length of stay (LOS) and postoperative LOS fell by 1.7 days (from 8.3 to 6.6 days, p=0.040) and 2 days (from 5.6 to 3.6 days, p=0.020) respectively. The higher ELC rate and the reduction in LOS produced additional tariff income (L111,930) and estimated savings in bed day (L90,440) and readmission (L27,252) costs. CONCLUSIONS: A dedicated ESU incorporating national recommendations for EGS improves alignment of best practice with best evidence and can also result in financial rewards for a busy district general hospital. PMID- 26673049 TI - Primary gallbladder lymphoma presenting with perforated cholecystitis and hyperamylasaemia. AB - Primary gallbladder lymphoma is rare. Perforated cholecystitis due to primary gallbladder lymphoma and not related to chemotherapy has been unreported. We report the case of an 80-year-old woman presenting with an acute abdomen and clinical peritonitis. Her serum amylase was raised to 878 iu/l. Urgent computed tomography revealed generalised free fluid with a normal pancreas and was non diagnostic as to the underlying pathology. An emergency laparotomy revealed bilious peritonitis with a necrotic patch on a distended gallbladder. A cholecystectomy was carried out and histology of the gallbladder revealed a marginal zone lymphoma. PMID- 26673050 TI - Partial salvage of avulsed tissue after dog bite. AB - Injuries to the nose can be severe from both a functional and cosmetic perspective. After suffering a dog bite to the central part of the face, an 18 year old woman underwent replantation of the avulsed tissue with the help of microsurgical arterial anastomosis. A venous anastomosis was impossible and venous congestion was treated with leech therapy. Subsequent skin necrosis occurred after a few days and the replantation was revised, revealing healthy tissue immediately below. The defect was covered with a full-thickness skin graft. At follow-up review eight months later, the functional and cosmetic result was satisfactory. To our knowledge, this is one of few cases where an injury of this severity healed with a cosmetically acceptable result. PMID- 26673051 TI - The use of a failed flap as a biological dressing. AB - A patient with a narrowly excised squamous cell carcinoma on the scalp underwent a wider excision that involved burring of the underlying calvarium. The defect was reconstructed with a superficial temporal artery pedicled flap, which unfortunately failed. The patient had multiple co-morbidities, limiting reconstructive options. The failed flap was therefore maintained as a 'biological dressing' for several weeks. During this time, the patient was reviewed regularly in the dressing clinic and did not develop a wound infection. Six weeks later, he was taken back to theatre and the flap was debrided under local anaesthesia. Beneath the flap, there was sufficient healthy granulation tissue over the site of previous bony debridement to permit split skin grafting. We advocate this technique as a useful method for managing difficult wounds in complex patients with multiple co-morbidities where other reconstructive techniques are limited. PMID- 26673052 TI - Lost tribe. PMID- 26673053 TI - Ligand-Free Synthesis of Tunable Size Ln:BaGdF5 (Ln = Eu3+ and Nd3+) Nanoparticles: Luminescence, Magnetic Properties, and Biocompatibility. AB - Bifunctional and highly uniform Ln:BaGdF5 (Ln = Eu(3+) and Nd(3+)) nanoparticles have been successfully synthesized using a solvothermal method consisting of the aging at 120 degrees C of a glycerol solution containing the corresponding Lanthanide acetylacetonates and butylmethylimidazolium tetrafluoroborate. The absence of any surfactant in the synthesis process rendered hydrophilic nanospheres (with tunable diameter from 45 nm 85 nm, depending on the cations concentration of the starting solution) which are suitable for bioapplications. The particles are bifunctional because they showed both optical and magnetic properties due to the presence of the optically active lanthanides (Eu(3+) in the visible and Nd(3+) in the NIR regions of the electromagnetic spectrum) and the paramagnetic gadolinium ion, respectively. The luminescence decay curves of the nanospheres doped with different amounts of Eu(3+) and Nd(3+) have been recorded in order to determine the optimum dopant concentration in each case, which turned out to be 5% Eu(3+) and 0.5% Nd(3+). Likewise, proton relaxation times were measured at 1.5 T in water suspensions of the optimum particles found in the luminescence study. The values obtained suggested that both kinds of particles could be used as positive contrast agents for MRI. Finally, it was demonstrated that both the 5% Eu(3+) and 0.5% Nd(3+)-doped BaGdF5 nanospheres showed negligible cytotoxicity for VERO cells for concentrations up to 0.25 mg mL(-1). PMID- 26673054 TI - The impending demise of the item in visual search. AB - The way the cognitive system scans the visual environment for relevant information - visual search in short - has been a long-standing central topic in vision science. From its inception as a research topic, and despite a number of promising alternative perspectives, the study of visual search has been governed by the assumption that a search proceeds on the basis of individual items (whether processed in parallel or not). This has led to the additional assumptions that shallow search slopes (at most a few tens of milliseconds per item for target-present trials) are most informative about the underlying process, and that eye movements are an epiphenomenon that can be safely ignored. We argue that the evidence now overwhelmingly favours an approach that takes fixations, not individual items, as its central unit. Within fixations, items are processed in parallel, and the functional field of view determines how many fixations are needed. In this type of theoretical framework, there is a direct connection between target discrimination difficulty, fixations, and reaction time (RT) measures. It therefore promises a more fundamental understanding of visual search by offering a unified account of both eye movement and manual response behaviour across the entire range of observed search efficiency, and provides new directions for research. A high-level conceptual simulation with just one free and four fixed parameters shows the viability of this approach. PMID- 26673055 TI - Physical fitness of secondary school adolescents in relation to the body weight and the body composition: classification according to World Health Organization. Part I. AB - BACKGROUND: Underweight and obesity are important factors affecting the level of physical fitness. The aim of this study was to assess physical fitness of lower secondary school adolescents in relation to BMI. METHODS: Two-hundred students, aged 14-16, were examined. Respondents were divided into 4 groups according to BMI classification. The body height and weight were determined. Physical fitness was assessed on the basis Zuchora's ISF tests. RESULTS: The body weight deficiency occurred in 3% of girls and 5% of boys, overweight was noted in 14% of both groups, and obesity in 6% and 12% accordingly. Statistically significant differences were determined in the components of physical fitness. They were noted in both genders between the group of children with standard body weight and overweight as well as obese children. Significant negative correlations were determined between and the components of physical fitness. More significant correlations giving evidence to the decrease of Zuchora's ISF score along with the increase of BMI were more significant in girls. CONCLUSIONS: Statistically significant differences between the boys and girls were determined in all five Zuchora's tests. The highest scores in physical fitness were achieved by the boys and girls with weight deficiency. PMID- 26673056 TI - Different competition approaches in a world-class 50-km racewalker during an Olympic year. AB - The aim of this case study was to compare the competition approaches for the Race Walking World Cup and the Olympic Games of a world-class 50-km racewalker. Total training volumes, intensity distribution, performance tests, high altitude stages and the evolution of his haematological values during the season were analysed. The last 12 weeks before the Race Walking World Cup (Approach 1) and the Olympic Games (Approach 2) were used for data analysis. Approach 1 was characterized by lower training volumes (791.7+/-192.8 min vs. 959.0+/-120.0 min ES=1.0, large effect) and a higher incidence of high intensity training (ES<0.8, large effect), than Approach 2. Approach 1 resulted in lower blood lactate values at set speeds, better haematological values and a better performance in the Race Walking World Cup than in the Olympic Games (3h47'30'' vs. 3h51'30"). According to the results of this analysis, it seems that a training strategy characterised by a higher incidence of high intensity training and lower volume of work may lead to superior training adaptations and performance in 50-km racewalking. This may help elite racewalkers and their coaches to achieve an optimum performance in their major goal competitions. PMID- 26673057 TI - Primary intramedullary neurocytoma: Case report and literature analysis. AB - BACKGROUND: Primary intramedullary neurocytoma is extremely rare. Due to its rarity, it is difficult to collect a wide series in a single institution to perform a survival analysis and give indications about prognosis and treatment. CASE DESCRIPTION: Here, we report on a case of a 37-year-old woman with primary intramedullary neurocytoma and perform a systematic statistical analysis of cases reported in the literature. Of 21 articles found, 15 studies and the present case (22 patients) were eligible for the analysis. We studied the impact of age, sex, number of involved levels (<=2 vs. >2), entity of resection, postoperative radiotherapy (RT), proliferation index (Ki67) on the neurological outcome of patients, and on the recurrence of the tumor. Comparison of categorical variables was performed by the chi (2) statistic. The Kaplan-Meier curves were plotted to calculate the progression-free survival (PFS) of these patients. P < 0.05 was considered as statistically significant. The 1-year PFS was 95.45% and the 2-year PFS was 86.36%. A gross total resection was associated to a worsening of the neurological function with no impact on the tumor recurrence. Adjuvant RT significantly improved the neurological function. A lower Ki67 was strongly associated with a lower tumor recurrence. CONCLUSIONS: We think that the goal of the surgery should be to preserve a good neurological function even if a residual tumor has to be left. Ki67 should be always evaluated due to its impact on the prognosis. Although adjuvant RT significantly improved the neurological function, its role in preventing the tumor recurrence is not clearly defined. PMID- 26673058 TI - The pathogenesis of rheumatoid arthritis in radiological studies. Part I and I. Sudol-Szopinska, K. Zaniewicz-Kaniewska, A. Warczynska, G. Matuszewska, F. Saied, W. Kunisz The pathogenesis of rheumatoid arthritis in radiological studies. Part II. PMID- 26673059 TI - Specific targeting and noninvasive imaging of breast cancer stem cells using single-walled carbon nanotubes as novel multimodality nanoprobes. AB - BACKGROUND: The limitation of current breast cancer treatments was elucidated by the presence of cancer stem cells (CSCs) that play essential role in cancer initiation, progression, resistance, recurrence and metastasis. Materials & methods: Biocompatible multimodality single-walled carbon nanotube (SWCNT) nanoprobes were developed. The biodistribution and preferential homing of CD44 antibody-conjugated SWCNTs toward the tumor site were monitored using MRI, single photon emission computed tomography and near-infrared fluorescence imaging noninvasive imaging modalities. RESULTS: Quantification of SWCNTs by sensitively measuring iron content in sorted CSC populations using inductively coupled plasma mass spectrometry confirmed the enhanced selective targeting of anti-CD44 SWCNT and immunohistochemistry analyses revealed enhanced colocalization with areas rich in CD44 receptors. DISCUSSION & CONCLUSION: This preclinical study provided encouraging results for efficient targeting of breast CSCs and perspectives for further clinical studies to confirm the efficacy and safety of the designed nanocarriers. PMID- 26673060 TI - Ultrasound quiz. PMID- 26673061 TI - Provider Agency Practices as a Source of Social Work EBP. AB - Through this article the authors propose that agency service provider systems may be a source of evidence-based practices (EBP). One agency's design and implementation of a program entitled Community Treatment and Rehabilitation is presented as an example. The elements of this program conform to the creation of EBPs. It was formulated with consideration of clients' values and judgments through their participation at every step in the assessment and treatment process. Staff clinicians were trained in established EBP interventions, such as cognitive therapy, embedded in a system of ordered assessment, treatment, and outcome evaluation. A controlled research design was used to gather outcome data to inform clinicians' decisions about interventions that were then systematically applied with clients. The delivery system was organized for clinical supervisors to guide staff clinical practices so that all were operating on the same set of guidelines allowing for similar outcomes to occur with similar interventions. This method of developing EBPs makes them available for application immediately and successfully eliminates the delay between development and implementation that usually occurs with other sources of EBPs. PMID- 26673062 TI - Psychological Gender and Emotional Intelligence in Youth Female Soccer Players. AB - Many sports (for instance soccer) are stereotypically perceived as a male activity. Even so, more and more women decide to become competitive athletes. Since the theory of sport requires comprehensive explanations and the practice of sport needs clear guidelines, interdisciplinary studies into the nature of sport, including its psychological aspects, are necessary. Analysing the psychological profile of female soccer players, particularly those who are about to become professional athletes, can provide many interesting insights into the specific character of female youth sport and show where improvements can be made in athletic training programmes (especially in mental training). It is therefore important to study psychological gender that determines social behaviours and to analyse female athletes' emotional intelligence. Emotional intelligence is defined as a set of emotional competencies that determine the effectiveness of human behaviours. Psychological gender and emotional intelligence have a significant effect on human adaptability and the efficiency of psychosocial functioning. This research was undertaken with the dual purpose of identifying the psychological gender and emotional intelligence of female soccer players. It involved 54 secondary-school girls, some of whom attended a sports class and others played on the Polish national team. The following tools were used to carry out the research: the Gender Assessment Inventory (IPP [This and the other acronyms derive from the Polish language]-developed by Kuczynska) and the Emotional Intelligence Questionnaire (INTE; created by Jaworowska and Matczak). As shown by the analysis of the results, most female soccer players in the study were androgynous and the level of their emotional intelligence was significantly higher than in other participants. This also seems to point to their significantly greater adaptability. At the same time, the level of emotional intelligence in many players was average or low, which seems insufficient and calls for adequate intervention measures to be taken. PMID- 26673077 TI - The near-atomic cryoEM structure of a flexible filamentous plant virus shows homology of its coat protein with nucleoproteins of animal viruses. AB - Flexible filamentous viruses include economically important plant pathogens. Their viral particles contain several hundred copies of a helically arrayed coat protein (CP) protecting a (+)ssRNA. We describe here a structure at 3.9 A resolution, from electron cryomicroscopy, of Pepino mosaic virus (PepMV), a representative of the genus Potexvirus (family Alphaflexiviridae). Our results allow modeling of the CP and its interactions with viral RNA. The overall fold of PepMV CP resembles that of nucleoproteins (NPs) from the genus Phlebovirus (family Bunyaviridae), a group of enveloped (-)ssRNA viruses. The main difference between potexvirus CP and phlebovirus NP is in their C-terminal extensions, which appear to determine the characteristics of the distinct multimeric assemblies - a flexuous, helical rod or a loose ribonucleoprotein. The homology suggests gene transfer between eukaryotic (+) and (-)ssRNA viruses. PMID- 26673078 TI - The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex. AB - The ability to recognize foreign double-stranded (ds)DNA of pathogenic origin in the intracellular environment is an essential defense mechanism of the human innate immune system. However, the molecular mechanisms underlying distinction between foreign DNA and host genomic material inside the nucleus are not understood. By combining biochemical assays and single-molecule techniques, we show that the nuclear innate immune sensor IFI16 one-dimensionally tracks long stretches of exposed foreign dsDNA to assemble into supramolecular signaling platforms. We also demonstrate that nucleosomes represent barriers that prevent IFI16 from targeting host DNA by directly interfering with these one-dimensional movements. This unique scanning-assisted assembly mechanism allows IFI16 to distinguish friend from foe and assemble into oligomers efficiently and selectively on foreign DNA. PMID- 26673079 TI - Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor. AB - Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 A resolution structure reveals selenium occupying the S2B site of FeMo cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 A, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis. PMID- 26673080 TI - S-glutathionylation of buccal cell proteins as biomarkers of exposure to hydrogen peroxide. AB - BACKGROUND: Exogenous or endogenous hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can lead to oxidation of cellular nucleophiles, particularly cysteines in proteins. Commercial mouthwashes containing H2O2 provide the opportunity to determine clinically whether changes in S-glutathionylation of susceptible proteins in buccal mucosa cells can be used as biomarkers of ROS exposure. METHODS: Using an exploratory clinical protocol, 18 disease-free volunteers rinsed with a mouthwash containing 1.5% H2O2 (442 mM) over four consecutive days. Exfoliated buccal cell samples were collected prior and post treatment and proteomics were used to identify S-glutathionylated proteins. RESULTS: Four consecutive daily treatments with the H2O2-containing mouthwash induced significant dose and time-dependent increases in S-glutathionylation of buccal cell proteins, stable for at least 30 min following treatments. Elevated levels of S-glutathionylation were maintained with subsequent daily exposure. Increased S-glutathionylation preceded and correlated with transcriptional activation of ROS sensitive genes, such as ATF3, and with the presence of 8 hydroxy deoxyguanosine. Data from a human buccal cell line TR146 were consistent with the trial results. We identified twelve proteins that were S glutathionylated following H2O2 exposure. CONCLUSIONS: Buccal cells can predict exposure to ROS through increased levels of S-glutathionylation of proteins. These post-translationally modified proteins serve as biomarkers for the effects of H2O2 in the oral cavity and in the future, may be adaptable as extrapolated pharmacodynamic biomarkers for assessing the impact of other systemic drugs that cause ROS and/or impact redox homeostasis. GENERAL SIGNIFICANCE: S glutathionylation of buccal cell proteins can be used as a quantitative measure of exposure to ROS. PMID- 26673082 TI - Association of Mean Platelet Volume with Severity, Serology & Treatment Outcome in Dengue Fever: Prognostic Utility. AB - BACKGROUND: Dengue is the most rapidly spreading mosquito-borne viral disease in the world. Dengue fever (DF) with its severe manifestations such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) has emerged as a major public health problem of international concern. Thrombocytopenia and bleeding are common complications of dengue fever, hence besides platelet counts, there is a need to assess the role of mean platelet volume. AIMS: Studying association of mean platelet volume (MPV) with severity, serology & treatment outcome to assess its prognostic utility, which can be of great help in limiting morbidity & mortality associated with dengue fever. MATERIALS AND METHODS: The present study was conducted in Central Pathology Lab of SMS Medical College & Hospital, Jaipur, Rajasthan from the period of March 2013 till October 2013. Blood samples were collected from 200 patients with NS 1 Antigen positivity experiencing febrile illness, clinically consistent with dengue infection. Evaluation of platelet counts, MPV, IgM and IgG antibodies was done in all these cases. STATISTICAL ANALYSIS: Categorical data were presented as numbers (percent) and were compared among groups using Chi-square test. Groups compared for demographic data were presented as mean and standard deviation and were compared using student t-test, ANOVA and Post-Hoc Test, Tukey Test using SPSS, version 20 for Windows. RESULTS: A total of 200 Dengue fever cases were studied. Out of which, 68% cases were of DF, 23% DHF & 9% DSS i.e. classical dengue fever was most common presentation. Maximum (44%) cases were in age group of 15-24 years. Fever was the presenting complaint in all cases (100%). 98% cases of dengue had thrombocytopenia. MPV showed no significant correlation with severity, serology & treatment outcome, thus excluding its role in dengue cases. CONCLUSION: Mean platelet volume is not important as prognostic parameter in dengue fever. PMID- 26673081 TI - Evaluation of the Nature of Collagen Fibers in KCOT, Dentigerous Cyst and Ameloblastoma using Picrosirius Red Stain - A Comparative Study. AB - BACKGROUND: Reciprocal interaction between dental epithelium and mesenchyme is thought to be crucial for normal odontogenesis. Thus, the mesenchymal influence of the fibrous capsules may play an important role in the maintenance of epithelial expression. Collagen is the major component of the extracellular matrix and possibly there is an alteration in the nature and structure of collagen in various pathological conditions. Studies by polarizing microscopy have also shown that there is a difference in collagen and probably these differences may play a role in their biologic behaviour. AIM: The purpose of this study was to evaluate the nature of collagen fibers in keratocystic odontogenic tumour (KCOT), dentigerous cyst (DC), unicystic ameloblastoma (UA) and solid/multicystic ameloblastoma (SMA) and correlating this with their biological behaviour. MATERIALS AND METHODS: Five diagnosed cases each of UA, SMA, KCOT and DC were taken and stained using Picrosirius red stain kit and evaluated using a polarizing microscope. STATISTICAL ANALYSIS: Chi-square test was used to analyse the results. RESULTS AND CONCLUSION: Collagen fibers in dentigerous cysts showed predominant yellowish-red birefringence and fibers in KCOT and ameloblastomas showed a predominantly greenish-yellow birefringence. Hence, our study suggests that the nature and character of collagen fibers may influence the clinical behaviour of the lesion. Since ours is a pilot study, to corroborate our view, studies with larger sample size are required to substantiate the results. PMID- 26673083 TI - Standards of the Polish Ultrasound Society - update. Ultrasound examination of the kidneys, ureters and urinary bladder. AB - The paper presents the principles of performing proper ultrasound examinations of the urinary tract. The following are discussed: preparation of patients, type of optimal apparatus, technique of examination and conditions which its description should fulfill. Urinary track examination in adults and in children constitutes an integral part of each abdominal examination. Such examinations should be performed with fasting patients or several hours after the last meal, with filled urinary bladder. APPARATUS: Ultrasound examinations in children and infants are performed using transducers with the frequency of 5.0-9.0 MHz and in adults - with the frequency of 2.0-6.0 MHz. Doppler options are desirable since they improve diagnostic capacity of sonography in terms of differentiation between renal focal lesions. SCANNING TECHNIQUE: Renal examinations are performed with the patients in the supine position. The right kidney is examined in the right hypochondriac region using the liver as the ultrasound "window." The left kidney is examined in the left hypochondriac region, preferably in the posterior axillary line. Ultrasound examinations of the upper segment of the ureters are performed after renal examination when the pelvicalyceal system is dilated. A condition necessary for a proper examination of the perivesical portion of the ureter is full urinary bladder. The scans of the urinary bladder are performed in transverse, longitudinal and oblique planes when the bladder is filled. DESCRIPTION OF THE EXAMINATION: The description should include patient's personal details, details of the referring unit, of the unit in which the examination is performed, examining physician's details, type of ultrasound apparatus and transducers as well as the description proper. PMID- 26673084 TI - Effect of Helicobacter pylori Infection on the Composition of Gastric Microbiota in the Development of Gastric Cancer. AB - BACKGROUND: Gastric cancer is one of the most common cancer types worldwide. In China, gastric cancer has become one of the major threats for public health, ranking second on incidence and third on cause of cancer death. Despite the common risk factors that promote the development of gastric cancer, the huge quantity of microorganism colonies within the gastrointestinal tract, particularly Helicobacter pylori infection, demonstrates a correlation with chronic inflammation and gastric carcinogenesis, as epidemiological studies have determined that H. pylori infection confers approximately 75% of the attributable risk for gastric cancer. SUMMARY: The current article draws an overview on the correlation between the microbiota, inflammation and gastric tumorigenesis. H. pylori infection has been identified as the main risk factor as it triggers epithelial barrier disruption, survival signaling as well as genetic/epigenetic modulation. Apart from H. pylori, the existence of a diverse and complex composition of microbiota in the stomach has been identified, which supports a role of microbiota in the development of gastric cancer. Moreover, metagenomics studies focused on the composition and function of the microbiota have associated microbiota with gastric metabolic diseases and even tumorigenesis. Apart from the gastric microbiota, inflammation is another identified contributor to cancer development as well. KEY MESSAGE: Though H. pylori infection and the non-H. pylori microbiota play a role in gastric cancer, the properties of gastric microbiota and mechanisms by which they participate in the genesis of gastric cancer are still not clearly depicted. Moreover, it remains to be understood how the presence of microbiota along with H. pylori infection affects the progress from gastric disease to cancer. PRACTICAL IMPLICATIONS: This article summarized a clue of the current studies on microbiota, H. pylori infection and the progression from gastric disease to cancer. PMID- 26673091 TI - Exceptionally high thermal sensitivity of rattlesnake TRPA1 correlates with peak current amplitude. AB - Extraordinary infrared-sensing ability of snake pit organs closely correlates with rich expression of TRPA1 transcripts in pit-innervating sensory neurons, strongly suggesting that TRPA1 is the molecular basis of the infrared detection. Here, it is shown that temperature coefficient Q10 (the fold current increase over 10 degrees C increase) of rattlesnake TRPA1 heterologously expressed in Xenopus oocytes increases proportionally to current amplitudes when appraised with two independent methods, the canonical Arrhenius plot analysis and newly devised Q10 scanning that assigns Q10 to each recorded temperature point. Moreover, for larger TRPA1 currents, the rise of Q10 from elevation of current sizes was steeper, yielding maximal Q10s up to ~100,000. TRPA1 from boas with less sensitive infrared-sensing ability was also sharply activated by temperature increase in oocytes, while Q10 rise from escalating current amplitudes was moderate compared to rattlesnake TRPA1. In contrast, thermal sensitivity of Drosophila TRPA1 was little dependent on current sizes, indicating that the steeply proportional current amplitude/thermosensitivity relationship is unique to the snake TRPA1s. Taken together, rattlesnake and boa TRPA1s are regulated to generate sufficient thermal sensitivity for infrared detection, providing an interesting context to further study the temperature-dependent activation mechanism of thermo-TRPs. PMID- 26673090 TI - Tasquinimod triggers an early change in the polarization of tumor associated macrophages in the tumor microenvironment. AB - BACKGROUND: Tasquinimod (a quinoline-3-carboxyamide) is a small molecule immunotherapy with demonstrated effects on the tumor microenvironment (TME) involving immunomodulation, anti-angiogenesis and inhibition of metastasis. A target molecule of tasquinimod is the inflammatory protein S100A9 which has been shown to affect the accumulation and function of suppressive myeloid cell subsets in tumors. Given the major impact of myeloid cells to the tumor microenvironment, manipulation of this cell compartment is a desirable goal in cancer therapeutics. METHODS: To understand the consequences of tasquinimod treatment on the TME, we evaluated early treatment effects in tumor infiltrating myeloid cells. Cellular phenotypes were studied by flow cytometry while gene expression both in tumor tissue and in isolated CD11b(+) cells or tumor cells were measured by real time PCR. Effects on angiogenesis were monitored by changes in CD31 levels and by gene expression in tumor tissue. Effects on cytokine levels in tumor tissue and serum were determined by multiplex analysis. RESULTS: The MC38-C215 colon carcinoma tumors showed a substantial infiltration of primarily myeloid cells that were dominated by Ly6C(low)F4/80(+)CD206(+) M2-polarized tumor associated macrophages (TAMs), an immuno-suppressive and pro-angiogenic cell population. Here, we show that tasquinimod treatment induces an anti-tumor effect which is subsequent to a reduction in tumor infiltrating CD206(+) M2 macrophages and a simultaneous increase in M1 macrophages expressing MHC class II and CD86. The tasquinimod induced changes in TAM polarization were evident within 24 h of exposure, emphasizing the ability of tasquinimod to rapidly reprogram the tumor microenvironment. This change in the tumor associated myeloid compartment preceded an increased IL12-production within the tumor and a decrease in tumor neovascularization. The switch in TAM polarization by tasquinimod was confirmed in the 4T1 breast cancer model where tasquinimod also reduce lung metastasis development. CONCLUSION: Our data show that tasquinimod affects tumor infiltrating myeloid cells early after exposure, leading to a change in phenotype from pro-angiogenic and immunosuppressive M2-like TAMs to pro-inflammatory M1 like macrophages. These changes are consistent with the effects of tasquinimod seen on tumor vascularization, immune suppression and metastasis giving further insights to the anti-tumor mechanism of action of tasquinimod. PMID- 26673092 TI - The interfacial properties of the peptide Polybia-MP1 and its interaction with DPPC are modulated by lateral electrostatic attractions. AB - Polybia-MP1 (IDWKKLLDAAKQIL-NH2), extracted from the Brazilian wasp Polybia paulista, exhibits a broad-spectrum bactericidal activity without being hemolytic and cytotoxic. In the present study, we analyzed the surface properties of the peptide and its interaction with DPPC in Langmuir monolayers. Polybia-MP1 formed stable monolayers, with lateral areas and surface potential values suggesting a mostly alpha-helical structure oriented near perpendicular to the membrane plane. In DPPC-peptide mixed monolayers, MP1 co-crystallized with the lipid forming branched domains only when the subphase was pure water. On subphases with high salt concentrations or at acidic or basic conditions, the peptide formed less densely packed films and was excluded from the domains, indicating the presence of attractive electrostatic interactions between peptides, which allow them to get closer to each other and to interact with DPPC probably as a consequence of a particular peptide arrangement. The residues responsible of the peptide-peptide attraction are suggested to be the anionic aspartic acids and the cationic lysines, which form a salt bridge, leading to oriented interactions in the crystal and thereby to branched domains. For this peptide, the balance between total attractive and repulsive interactions may be finely tuned by the aqueous ionic strength and pH, and since this effect is related with lysines and aspartic acids, similar effects may also occur in other peptides containing these residues in their sequences. PMID- 26673093 TI - [Well-being, quality of life and affect regulation in Portuguese adolescents]. AB - OBJECTIVES: The objective of this study is to examine the emotional regulation, quality of life, and subjective well-being in adolescence, taking into account individual and family differences, as well as gender, age and educationlevel of parents. Relationships between the questionnaires wariables were also considered. DESIGN: Descriptive-comparative, cross-sectional, and quantitative study. LOCATION: Two schools in the north of Portugal. PARTICIPANTS: The sample was selected for convenience due to geographic proximity. INCLUSION CRITERIA: adolescents with age between 12 and 18 years old, from compulsory courses and without any special difficulty. Total sample: 619, valid sample: 602. MAIN MEASUREMENTS: Personal Wellness; Health Questionnaire SF-8 (quality of life); and the Measurement of Affect Regulation Styles-trait version Questionnaire. RESULTS: There were no differences between well-being and gender. Health perception is better for boys, and affect regulation for girls. In relation to age, there are negative correlations mainly with variables from the health questionnaire. Significant differences in relation to study level of parents were observed. Main correlations were found between wellness and health variables. CONCLUSIONS: The influence of the education level of parents and age have differentiating role, mainly for well-being and quality of life. From a promotion of wellness perspective in adolescence, potential of health perception and some emotional regulation strategies should be considered in interventions and health education strategy. PMID- 26673094 TI - Effects of Temperature on Systemic Infection and Symptom Expression of Turnip mosaic virus in Chinese cabbage (Brassica campestris). AB - Using the Chinese cabbage (Brassica campestris) cultivar 'Chun-goang' as a host and turnip mosaic virus (TuMV) as a pathogen, we studied the effects of ambient temperature (13 degrees C, 18 degrees C, 23 degrees C, 28 degrees C and 33 degrees C) on disease intensity and the speed of systemic infection. The optimal temperature for symptom expression of TuMV was 18-28 degrees C. However, symptoms of viral infection were initiated at 23-28 degrees C and 6 days post infection (dpi). Plants maintained at 33 degrees C were systemically infected as early as 6 dpi and remained symptomless until 12 or 22 dpi, depending on growth stage at the time of inoculation. It took 45 days for infection of plants grown at 13 degrees C. Quantitative real-time polymerase chain reaction (q-PCR) results showed that the accumulation of virus coat protein was greater in plants grown at 23-28 degrees C. The speed of systemic infection increased linearly with rising ambient temperature, up to 23 degrees C. The zero-infection temperature was 10.1 degrees C. To study the effects of abruptly elevated temperatures on systemic infection, plants inoculated with TuMV were maintained at 10 degrees C for 20 d; transferred to a growth chamber at temperatures of 13 degrees C, 18 degrees C, 23 degrees C, 28 degrees C, or 33 degrees C for 1, 2, or 3 d; and then moved back to 10 degrees C. The numbers of plants infected increased as duration of exposure to higher temperatures and dpi increased. PMID- 26673097 TI - Editorial Comment. PMID- 26673096 TI - Genetic variants in Nogo receptor signaling pathways may be associated with early life adversity in schizophrenia susceptibility. AB - BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder thought to result from abnormal brain development. Nogo, an oligodendrocyte bound molecule, signals by binding to the Nogo receptor (NgR) located on axonal membranes. The NgR co receptors include p75 neurotrophin receptor or TNF receptor orphan Y (TROY). Nogo signaling is responsible for central nervous system myelin regulation and neurite outgrowth during neurodevelopment, and plasticity in the mature brain. METHODS: We examined single nucleotide polymorphisms (SNPs) in NgR, p75, and TROY receptor genes and downstream signaling partner With No Lysine (K) (WNK1) and Myelin transcription factor 1-like (Myt1l) genes in an Australian case-control schizophrenia cohort (n = 268/group). High-throughput SNP genotyping was performed using the MassARRAY(r) genotyping assay. RESULTS: Analysis revealed a significant association between the Myt1l SNP rs2304008 and female schizophrenia subjects. The WNK1 SNP rs1468326 and the Myt1l SNP rs3748988 showed significant associations with schizophrenia in subjects with a maternal mental history and in subjects who experienced childhood trauma respectively. Following Bonferroni correction, all significance was lost. CONCLUSIONS: Despite the lack of positive findings in our population after correction for multiple testing, previous gene expression and association studies in schizophrenia suggest the implication of NgR signaling pathway genes in the etiology of schizophrenia remains topical and timely. GENERAL SIGNIFICANCE: Further investigations will be necessary to fully assess the role of these genes in the pathophysiology of schizophrenia. However these genes may prove useful in further understanding the mechanism by which negative experiences early in life can affect myelin-related processes in the context of schizophrenia. PMID- 26673095 TI - An Examination of Lower Extremity Function and its Correlates in Older African American and White Men. AB - OBJECTIVE: Maintaining functional status and reducing/eliminating health disparities in late life are key priorities. Older African Americans have been found to have worse lower extremity functioning than Whites, but little is known about potential differences in correlates between African American and White men. The goal of this investigation was to examine measures that could explain this racial difference and to identify race-specific correlates of lower extremity function. METHODS: Data were analyzed for a sample of community-dwelling men. Linear regression models examined demographics, medical conditions, health behaviors, and perceived discrimination and mental health as correlates of an objective measure of lower extremity function, the Short Physical Performance Battery (SPPB). Scores on the SPPB have a potential range of 0 to 12 with higher scores corresponding to better functioning. RESULTS: The mean age of all men was 74.9 years (SD=6.5), and the sample was 50% African American and 53% rural. African American men had scores on the SPPB that were significantly lower than White men after adjusting for age, rural residence, marital status, education, and income difficulty (P<.01). Racial differences in cognitive functioning accounted for approximately 41% of the race effect on physical function. Additional models stratified by race revealed a pattern of similar correlates of the SPPB among African American and White men. CONCLUSIONS: The results of this investigation can be helpful for researchers and clinicians to aid in identifying older men who are at-risk for poor lower extremity function and in planning targeted interventions to help reduce disparities. PMID- 26673098 TI - Interactome of the hepatitis C virus: Literature mining with ANDSystem. AB - A study of the molecular genetics mechanisms of host-pathogen interactions is of paramount importance in developing drugs against viral diseases. Currently, the literature contains a huge amount of information that describes interactions between HCV and human proteins. In addition, there are many factual databases that contain experimentally verified data on HCV-host interactions. The sources of such data are the original data along with the data manually extracted from the literature. However, the manual analysis of scientific publications is time consuming and, because of this, databases created with such an approach often do not have complete information. One of the most promising methods to provide actualisation and completeness of information is text mining. Here, with the use of a previously developed method by the authors using ANDSystem, an automated extraction of information on the interactions between HCV and human proteins was conducted. As a data source for the text mining approach, PubMed abstracts and full text articles were used. Additionally, external factual databases were analyzed. On the basis of this analysis, a special version of ANDSystem, extended with the HCV interactome, was created. The HCV interactome contains information about the interactions between 969 human and 11 HCV proteins. Among the 969 proteins, 153 'new' proteins were found not previously referred to in any external databases of protein-protein interactions for HCV-host interactions. Thus, the extended ANDSystem possesses a more comprehensive detailing of HCV-host interactions versus other existing databases. It was interesting that HCV proteins more preferably interact with human proteins that were already involved in a large number of protein-protein interactions as well as those associated with many diseases. Among human proteins of the HCV interactome, there were a large number of proteins regulated by microRNAs. It turned out that the results obtained for protein-protein interactions and microRNA-regulation did not depend on how well the proteins were studied, while protein-disease interactions appeared to be dependent on the level of study. In particular, the mean number of diseases linked to well-studied proteins (proteins were considered well-studied if they were mentioned in 50 or more PubMed publications) from the HCV interactome was 20.8, significantly exceeding the mean number of associations with diseases (10.1) for the total set of well-studied human proteins present in ANDSystem. For proteins not highly poorly-studied investigated, proteins from the HCV interactome (each protein was referred to in less than 50 publications) distribution of the number of diseases associated with them had no statistically significant differences from the distribution of the number of diseases associated with poorly-studied proteins based on the total set of human proteins stored in ANDSystem. With this, the average number of associations with diseases for the HCV interactome and the total set of human proteins were 0.3 and 0.2, respectively. Thus, ANDSystem, extended with the HCV interactome, can be helpful in a wide range of issues related to analyzing HCV-host interactions in the search for anti-HCV drug targets. The demo version of the extended ANDSystem covered here containing only interactions between human proteins, genes, metabolites, diseases, miRNAs and molecular-genetic pathways, as well as interactions between human proteins/genes and HCV proteins, is freely available at the following web address: http://www-bionet.sscc.ru/psd/andhcv/. PMID- 26673099 TI - CORRIGENDUM. AB - [This corrects the article on p. 877 in vol. 10, PMID: 15976421.]. PMID- 26673100 TI - Should we be promoting embryo transfer at blastocyst stage? AB - Improved laboratory standards and better culture media have made extended culture to blastocyst stage a reality to identify embryos with maximum implantation potential. The strategy of extended culture has become more popular across the world at a time when regulatory bodies have emphasized the need to increase the uptake of elective single embryo transfer, minimize complications associated with multiple births and aim for a healthy singleton live-birth as the preferred outcome in IVF. New data on perinatal outcomes suggest that pregnancies after embryo transfer at blastocyst stage are associated with a higher risk of preterm delivery, large for gestational age babies, monozygotic twins and altered sex ratio compared with those following embryo transfers at cleavage stage. In addition, concerns have been raised of increased congenital anomalies and epigenetic modifications with embryo transfer at blastocyst stage. Twenty-four years on from the first embryo transfer at blastocyst stage, we examine the reasons for extended embryo culture, evaluate the risks and benefits of this strategy and suggest the need to reconsider this policy in the interests of fetal safety. PMID- 26673101 TI - Genetic variants of vascular endothelial growth factor are associated with recurrent implantation failure in Korean women. AB - Vascular endothelial growth factor (VEGF) is involved in embryonic development, decidual vascularization and placenta angiogenesis. This study was performed to determine whether there is an association between genetic polymorphisms in the VEGF gene and the development of recurrent implantation failure (RIF) in Korean women. A total of 119 women diagnosed with RIF and 236 control subjects were genotyped for VEGF polymorphic sites including rs833061 (-460T>C), rs25648 ( 7C>T) and rs3025020 (-583C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays and real-time PCR. The VEGF rs833061 C allele and rs25648 T allele were significantly associated with increased RIF risk (odds ratio [OR] = 1.813 [1.161-2.831], P = 0.009, OR = 2.213 [1.254-3.903], P = 0.005). The rs833061/rs25648 TC/CT, TC/CT+TT, and rs833061/rs3025020 TC+CC/TT genotypes were more frequent in the RIF group compared with the control group (OR = 2.130 [1.092-4.156], P = 0.025, OR = 2.130 [1.092-4.156], OR = 4.261 [1.163-15.620], P = 0.028, respectively). The results of this study suggests that VEGF polymorphisms are associated with RIF development. Therefore, we postulate that VEGF polymorphisms might be useful markers to predict RIF development. Further studies are warranted to elucidate the role of VEGF variants and RIF development. PMID- 26673102 TI - Insertion/deletion polymorphism in intron 16 of ACE gene in idiopathic recurrent spontaneous abortion: case-control study, systematic review and meta-analysis. AB - The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin I converting enzyme gene (ACE) has been extensively studied as a predisposing factor for idiopathic recurrent spontaneous abortion (IRSA). A case-control study including 149 women with >=3 spontaneous abortions and 149 controls was performed to test the association of ACE I/D polymorphism with IRSA. A systematic review was conducted of previous case-control studies, with strict selection criteria for meta-analyses. We also aimed to evaluate the potential differences in summary estimates between studies defining IRSA as >=2 and >=3 spontaneous abortions. Genotyping was performed by PCR, and systematic review conducted using PubMed and Scopus. There was no association of the polymorphism with IRSA in Slovenian women. Sixteen case-control studies, showing substantial differences regarding IRSA definition and selection criteria for women were identified. Meta-analysis was performed and included four studies defining IRSA as >=2 spontaneous abortions and the current study, which defined IRSA as >=3 spontaneous abortions. Based on random effects model, meta-analysis conducted on 1192 patients and 736 controls showed no association with IRSA under dominant(DD+IDvsII) and recessive(DDvsID+II) genetic models. Well-designed studies are needed to evaluate the role of ACE I/D polymorphism in IRSA defined as >=3 spontaneous abortions. PMID- 26673103 TI - Spontaneous clinical pregnancy following GNRH agonist trigger for final oocyte maturation and freeze-all approach: a case report. AB - We herein describe a 34-year old infertile woman with polycystic ovary syndrome who was underwent follicle stimulation with a gonadotrophin-releasing hormone (GnRH) agonist, and a freeze-all approach, but still conceived spontaneously without any luteal phase support and without development of ovarian hyperstimulation syndrome. The bilateral antral follicle count of the patient was 22. A fixed GnRH antagonist protocol was used. As the number of follicles wider than 11 mm in diameter on the day of stimulation was 28, the final oocyte maturation was triggered by a GnRH agonist and a freeze-all approach was taken. Although no luteal phase support was used after trigger, the patient conceived spontaneously. In conclusion, the endogenous LH level during the luteal phase may be sufficiently high in selected cases to rescue some of the corpora lutea even when a GnRH agonist has been administered for final oocyte maturation. When a freeze-all approach is taken to avoid ovarian hyperstimulation syndrome, couples should be strictly advised to refrain from sexual intercourse after oocyte retrieval. PMID- 26673104 TI - Abstracts: VI Scandinavian COPD Research Symposium Published with support from Boehringer Ingelheim. PMID- 26673106 TI - Associations with resuscitation choice: Do not resuscitate, full code or undecided. AB - OBJECTIVE: To examine associations of individual exposure and knowledge of resuscitation mechanics and prognosis with specific decision: Do Not Resuscitate (DNR), Full Code (FC) or Undecided (UD). METHODS: Cross-sectional questionnaire at 3 sites: geriatric assessment center, internal medicine resident clinic, and inpatient palliative care service. RESULTS: 407 completed the questionnaire: 27% identified as DNR, 24% as FC and 49% as UD. Few (11.8%) respondents reported discussion of DNR status with their primary care doctor. DNR choice was associated with knowledge of DNR mechanics, OR=2.30 (95%CI: 1.23-4.30), physician discussion, OR=5.58 (95%CI: 2.39-13.04) and confidence in understanding own health problems, OR=2.89 (95%CI: 1.04-8.04). FC choice was associated with knowledge of FC mechanics, OR=2.01 (95%CI: 1.03-3.93) and media code exposure, OR=3.80 (95%CI: 1.46-9.92). Knowledge of resuscitation prognosis was negatively associated with FC, OR =0.48 (95%CI: 0.23-0.98). CONCLUSION: Many individuals lack knowledge or understanding of resuscitation procedure, its risks, and prognosis. Educational efforts, for both patients and healthcare professionals, are needed to improve individual knowledge needed for informed decision. PRACTICE IMPLICATIONS: Scheduled time for physician-patient discussion remains important for education about individual health conditions and risk/benefits related to resuscitation. PMID- 26673105 TI - Multiple protein-protein interactions converging on the Prp38 protein during activation of the human spliceosome. AB - Spliceosomal Prp38 proteins contain a conserved amino-terminal domain, but only higher eukaryotic orthologs also harbor a carboxy-terminal RS domain, a hallmark of splicing regulatory SR proteins. We show by crystal structure analysis that the amino-terminal domain of human Prp38 is organized around three pairs of antiparallel alpha-helices and lacks similarities to RNA-binding domains found in canonical SR proteins. Instead, yeast two-hybrid analyses suggest that the amino terminal domain is a versatile protein-protein interaction hub that possibly binds 12 other spliceosomal proteins, most of which are recruited at the same stage as Prp38. By quantitative, alanine surface-scanning two-hybrid screens and biochemical analyses we delineated four distinct interfaces on the Prp38 amino terminal domain. In vitro interaction assays using recombinant proteins showed that Prp38 can bind at least two proteins simultaneously via two different interfaces. Addition of excess Prp38 amino-terminal domain to in vitro splicing assays, but not of an interaction-deficient mutant, stalled splicing at a precatalytic stage. Our results show that human Prp38 is an unusual SR protein, whose amino-terminal domain is a multi-interface protein-protein interaction platform that might organize the relative positioning of other proteins during splicing. PMID- 26673107 TI - Health beliefs and desire to improve cholesterol levels among patients with hyperlipidemia. AB - OBJECTIVE: Because hyperlipidemia is asymptomatic, many veterans affairs (VA) patients may not perceive it seriously. We assessed key Health Belief model concepts to describe patients' cholesterol-related health beliefs and examine associations between patient-level factors and desire to improve cholesterol control. METHODS: We used baseline data from an ongoing randomized clinical trial. Eligible patients were receiving care at the Durham VA and had CVD risk total cholesterol levels >130 mg/dL and/or <80% medication adherence in the previous 12 months. A survey assessed patients' health beliefs about high cholesterol and self-reported medication adherence. Multivariable logistic regression examined whether there was an association between desire to control cholesterol and cholesterol status. RESULTS: Approximately 64% (n=155) of patients perceived high cholesterol as 'very serious'. In multivariable logistic regression analysis, patients who perceived high cholesterol as 'very serious' (OR 2. 26, p=0.032) and/or with high self-efficacy (OR 4.70, p<0.001) had increased odds of desiring cholesterol control. CONCLUSION: The factors most significantly associated with desire to improve cholesterol control were perceiving hyperlipidemia as 'very serious and self-efficacy for cholesterol control. PRACTICE IMPLICATION: Educating patients, with the goal of appropriately increasing their perceived risk of disease, is likely necessary to impact cholesterol control. PMID- 26673108 TI - Enhancing clinical decisions about care through a pre-consultation sheet that captures patients' views on their health conditions and treatments: A qualitative study in the field of chronic pain. AB - OBJECTIVE: This study examined whether and how a pre-consultation sheet (PCS) that captures patients' views on their condition and treatments can facilitate doctors in identifying targets for medical advice. METHODS: A PCS in the form of a list of questions was developed and implemented in chronic pain consultations. Its value was examined through video-recordings and post-consultation interviews with doctors and patients. RESULTS: Doctors reported that the PCS helped them identify topics that required further discussion with patients, unexpected information, patients' expectations on outcomes, and their attitudes and beliefs about treatments. Patients reported that the PCS helped them collect and structure their views, reduced their anxiety regarding the encounter, and created a setting in which they felt heard. CONCLUSION: The PCS captures patients' views that are valuable in helping doctors identify targets of intervention. It focuses on aspects that matter to patients and that enrich information sharing beyond medical records. PRACTICE IMPLICATIONS: Addressing patients' views on health conditions and treatments facilitates doctors and patients in defining targets for intervention. It assists doctors in tailoring their advice and helps patients present their case. A PCS seems to be a feasible and acceptable instrument to support doctors and patients in this information sharing. PMID- 26673112 TI - Training-induced changes in subsequent-memory effects: No major differences among children, younger adults, and older adults. AB - The neural correlates of encoding mode, or the state of forming new memory episodes, have been found to change with age and mnemonic training. However, it is unclear whether neural correlates of encoding success, termed subsequent memory (SM) effects, also differ by age and mnemonic skill. In a multi-session training study, we investigated whether SM effects are altered by instruction and training in a mnemonic skill, and whether such alterations differ among children, younger adults, and older adults. Before and after strategy training, fMRI data were collected while participants were memorizing word pairs. In all age groups, participants receiving training showed greater performance gains than control group participants. Analysis of task-relevant regions showed training-induced reductions in SM effects in left frontal regions. Reductions in SM effects largely generalized across age and primarily reflected greater training-induced activation increases for omissions than for remembered items, indicating that training resulted in more consistent use of the mnemonic strategy. The present results reveal no major age differences in SM effects in children, younger adults, and older adults. PMID- 26673113 TI - Thinking about thinking: Neural mechanisms and effects on memory. AB - It is a well-established finding that memory encoding is impaired if an external secondary task (e.g. tone discrimination) is performed simultaneously. Yet, while studying we are also often engaged in internal secondary tasks such as planning, ruminating, or daydreaming. It remains unclear whether such a secondary internal task has similar effects on memory and what the neural mechanisms underlying such an influence are. We therefore measured participants' blood oxygenation level dependent responses while they learned word-pairs and simultaneously performed different types of secondary tasks (i.e., internal, external, and control). Memory performance decreased in both internal and external secondary tasks compared to the easy control condition. However, while the external task reduced activity in memory-encoding related regions (hippocampus), the internal task increased neural activity in brain regions associated with self-reflection (anterior medial prefrontal cortex), as well as in regions associated with performance monitoring and the perception of salience (anterior insula, dorsal anterior cingulate cortex). Resting-state functional connectivity analyses confirmed that anterior medial prefrontal cortex and anterior insula/dorsal anterior cingulate cortex are part of the default mode network and salience network, respectively. In sum, a secondary internal task impairs memory performance just as a secondary external task, but operates through different neural mechanisms. PMID- 26673115 TI - How does language distance between L1 and L2 affect the L2 brain network? An fMRI study of Korean-Chinese-English trilinguals. AB - The present study tested the hypothesis that language distance between first language (L1) and second language (L2) influences the assimilation and accommodation pattern in Korean-Chinese-English trilinguals. The distance between English and Korean is smaller than that between Chinese and Korean in terms of orthographic transparency, because both English and Korean are alphabetic, whereas Chinese is logographic. During fMRI, Korean trilingual participants performed a visual rhyming judgment task in three languages (Korean: KK, Chinese: KC, English: KE). Two L1 control groups were native Chinese and English speakers performing the task in their native languages (CC and EE, respectively). The general pattern of brain activation of KC was more similar to that of CC than KK, suggesting accommodation. Higher accuracy in KC was associated with decreased activation in regions of the KK network, suggesting reduced assimilation. In contrast, the brain activation of KE was more similar to that of KK than EE, suggesting assimilation. Higher accuracy in KE was associated with decreased activation in regions of the EE network, suggesting reduced accommodation. Finally, an ROI analysis on the left middle frontal gyrus revealed greater activation for KC than for KE, suggesting its selective involvement in the L2 with more arbitrary mapping between orthography and phonology (i.e., Chinese). Taken together, the brain network involved in L2 reading is similar to the L1 network when L2 and L1 are similar in orthographic transparency, while significant accommodation is expected when L2 is more opaque than L1. PMID- 26673116 TI - Individual and Clustered Rankability of ICUs According to Case-Mix-Adjusted Mortality. AB - OBJECTIVES: The performance of ICUs can be compared by ranking them into a league table according to their risk-adjusted mortality rate. The statistical quality of a league table can be expressed as its rankability, the percentage of variation between ICUs attributable to unexplained differences. We examine whether we can improve the rankability of our league table by using data from a longer period or by grouping ICUs with similar performance constructing a league table of clusters rather than individual ICUs. DESIGN: We developed a league table for risk adjusted mortality rate with its rankability. The effect of assessment period was determined using a resampling procedure. Hierarchical clustering was used to obtain clusters of similar ICUs. PATIENTS: We used data from ICUs participating in the Dutch National Intensive Care Evaluation registry between 2011 and 2013. MEASUREMENTS AND MAIN RESULTS: We constructed league tables using 157,394 admissions from 78 ICUs with risk-adjusted mortality rate between 5.9% and 13.9% per ICU over the inclusion period. The rankability was 73% for 2013 and 89% for the whole period 2011-2013. Rankability over the year 2013 increased till 98% when clustering ICUs, reaching an optimum at a league table of seven clusters. CONCLUSIONS: We conclude that, when using data from a single year, the rankability of a league table of Dutch ICUs based on risk-adjusted mortality rate was unacceptably low. We could improve the rankability of this league table by increasing the period of data collection or by grouping similar ICUs into clusters and constructing a league table of clusters of ICUs rather than individual ICUs. Ranking clusters of ICUs could be useful for identifying possible differences in performance between clusters of ICUs. PMID- 26673114 TI - The origins of metamodality in visual object area LO: Bodily topographical biases and increased functional connectivity to S1. AB - Recent evidence from blind participants suggests that visual areas are task oriented and sensory modality input independent rather than sensory-specific to vision. Specifically, visual areas are thought to retain their functional selectivity when using non-visual inputs (touch or sound) even without having any visual experience. However, this theory is still controversial since it is not clear whether this also characterizes the sighted brain, and whether the reported results in the sighted reflect basic fundamental a-modal processes or are an epiphenomenon to a large extent. In the current study, we addressed these questions using a series of fMRI experiments aimed to explore visual cortex responses to passive touch on various body parts and the coupling between the parietal and visual cortices as manifested by functional connectivity. We show that passive touch robustly activated the object selective parts of the lateral occipital (LO) cortex while deactivating almost all other occipital-retinotopic areas. Furthermore, passive touch responses in the visual cortex were specific to hand and upper trunk stimulations. Psychophysiological interaction (PPI) analysis suggests that LO is functionally connected to the hand area in the primary somatosensory homunculus (S1), during hand and shoulder stimulations but not to any of the other body parts. We suggest that LO is a fundamental hub that serves as a node between visual-object selective areas and S1 hand representation, probably due to the critical evolutionary role of touch in object recognition and manipulation. These results might also point to a more general principle suggesting that recruitment or deactivation of the visual cortex by other sensory input depends on the ecological relevance of the information conveyed by this input to the task/computations carried out by each area or network. This is likely to rely on the unique and differential pattern of connectivity for each visual area with the rest of the brain. PMID- 26673117 TI - Tibial Tunnel Cyst Formation after Anterior Cruciate Ligament Reconstruction Using a Non-Bioabsorbable Interference Screw. AB - Tibial cyst formation following the use of bioabsorbable interference screws in anterior cruciate ligament (ACL) reconstruction is well-described; however, cyst formation after the use of metallic interference screws is not well-documented. We describe a case of osteolytic lesion of the proximal tibia presenting to us 20 years after ACL reconstruction using an autologous bone-tendon-bone graft. The original graft fixation technique was interference fixation with a metal screw in the tibial and femoral tunnels. A two-stage revision reconstruction of the ACL was undertaken with curettage and bone grafting of the tibial lesion in the first stage and reconstruction using a four-strand hamstring tendon in the second stage. The patient recovered satisfactorily with complete healing of the cyst and returned to pre-injury level of activities. We have reviewed case reports and case series that describe the aetiology of intra-osseous cyst formation following ACL reconstruction. PMID- 26673118 TI - Bundle-like alpha'-NaV2O5 mesocrystals: from synthesis, growth mechanism to analysis of Na-ion intercalation/deintercalation abilities. AB - Bundle-like alpha'-NaV2O5 mesocrystals were synthesized successfully by a two step hydrothermal method. Observations using electron microscopy revealed that the obtained NaV2O5 mesocrystals were composed of nanobelts with the preferential growth direction of [010]. The precise crystal structure was further confirmed by Rietveld refinement and Raman spectroscopy. Based on analysis of crystal structure and microscopy, a reaction and growth mechanism, hydrolysis condensation (oxolation and olation)-ion exchange-self-assembly, was proposed and described in detail. Furthermore, electrochemical measurements were used to analyze the Na-ions intercalation/deintercalation abilities in NaV2O5, and indicated that Na-ions were difficult to extract. Importantly, the DFT theoretical calculation results, which showed that the migration energy of Na ions was so huge that migration of Na-ions was quite difficult, can explain and support well the results of the electrochemical measurements. PMID- 26673119 TI - Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. AB - The programmed death 1 (PD-1) receptor is expressed by activated T-cells and engaged by ligands PD-L1 and PD-L2 normally expressed by infiltrating immune cells in response to viral infection. The PD-1/PD-L1 axis is a negative inhibitory pathway that down-regulates T-cells but is also used by tumors to evade anti-tumor immunity. Antibodies targeting PD-1/PD-L1 axis are capable of restoring functional anti-tumor immunity and have demonstrated efficacy in a broad range of tumor types including non-small cell lung cancer in both squamous and adenocarcinoma histologies. Ongoing issues affecting clinical development of these agents include assessment of response, optimal duration of therapy in excellent responders, predictive biomarkers and mechanisms of resistance. In this report, we describe a patient with advanced KRAS mutant heavily pretreated pulmonary adenocarcinoma who developed an excellent response after a single-dose of nivolumab. Pre-treatment tumor was found to have moderate CD3 and PD-L1 positivity by immunohistochemical staining. Evaluation of exceptional responders and non-responders are critical to furthering our understanding of the mechanisms of action (and resistance) to these agents. PMID- 26673120 TI - Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system. AB - Brown adipose tissue (BAT) plays a central role in regulating energy homeostasis, and may provide novel strategies for the treatment of human obesity. BAT-mediated thermogenesis is regulated by mitochondrial uncoupling protein 1 (UCP1) in classical brown and ectopic beige adipocytes, and is controlled by sympathetic nervous system (SNS). Previous work indicated that fish oil intake reduces fat accumulation and induces UCP1 expression in BAT; however, the detailed mechanism of this effect remains unclear. In this study, we investigated the effect of fish oil on energy expenditure and the SNS. Fish oil intake increased oxygen consumption and rectal temperature, with concomitant upregulation of UCP1 and the beta3 adrenergic receptor (beta3AR), two markers of beige adipocytes, in the interscapular BAT and inguinal white adipose tissue (WAT). Additionally, fish oil intake increased the elimination of urinary catecholamines and the noradrenaline (NA) turnover rate in interscapular BAT and inguinal WAT. Furthermore, the effects of fish oil on SNS-mediated energy expenditure were abolished in transient receptor potential vanilloid 1 (TRPV1) knockout mice. In conclusion, fish oil intake can induce UCP1 expression in classical brown and beige adipocytes via the SNS, thereby attenuating fat accumulation and ameliorating lipid metabolism. PMID- 26673121 TI - Are Risks From Medical Imaging Still too Small to Be Observed or Nonexistent? AB - Several radiation-related professional societies have concluded that carcinogenic risks associated with doses below 50-100 mSv are either too small to be detected, or are nonexistent. This is especially important in the context of doses from medical imaging. Radiation exposure to the public from medical imaging procedures is rising around the world, primarily due to increased utilization of computed tomography. Professional societies and advisory bodies consistently recommend against multiplying small doses by large populations to predict excess radiation induced cancers, in large part because of the potential for sensational claims of health impacts which do not adequately take the associated uncertainties into account. Nonetheless, numerous articles have predicted thousands of future cancers as a result of CT scanning, and this has generated considerable concern among patients and parents. In addition, some authors claim that we now have direct epidemiological evidence of carcinogenic risks from medical imaging. This paper critically examines such claims, and concludes that the evidence cited does not provide direct evidence of low-dose carcinogenicity. These claims themselves have adverse public health impacts by frightening the public away from medically justified exams. It is time for the medical and scientific communities to be more assertive in responding to sensational claims of health risks. PMID- 26673123 TI - Multiple Giant Sebaceous Cysts of Scalp. AB - Sebaceous cyst is an epidermal cyst often found on the hairy areas of the body such as scalp, trunk and face. Though commonly encountered in surgical practice, its presentation as multiple giant sebaceous cysts over scalp is rare. However, in long standing cases malignant transformation has also been sparingly reported. We report a case of a 52-year-old male presenting with multiple large sized swellings on the scalp, seven in number. These were present since childhood and gradually progressed to the enormous size of largest measuring 10cm x 8cm. Excision of these cysts was undertaken and specimens were sent for histopathological examination which confirmed the nature of these cysts to be sebaceous cysts. No malignant changes were reported in any of the specimens. The patient was followed up and was doing well. PMID- 26673125 TI - Advancing Health Equity: Honoring the Legacy of Dr. Elijah B. Saunders. PMID- 26673124 TI - SMC1B is present in mammalian somatic cells and interacts with mitotic cohesin proteins. AB - Cohesin is an evolutionarily conserved protein complex that plays a role in many biological processes: it ensures faithful chromosome segregation, regulates gene expression and preserves genome stability. In mammalian cells, the mitotic cohesin complex consists of two structural maintenance of chromosome proteins, SMC1A and SMC3, the kleisin protein RAD21 and a fourth subunit either STAG1 or STAG2. Meiotic paralogs in mammals were reported for SMC1A, RAD21 and STAG1/STAG2 and are called SMC1B, REC8 and STAG3 respectively. It is believed that SMC1B is only a meiotic-specific cohesin member, required for sister chromatid pairing and for preventing telomere shortening. Here we show that SMC1B is also expressed in somatic mammalian cells and is a member of a mitotic cohesin complex. In addition, SMC1B safeguards genome stability following irradiation whereas its ablation has no effect on chromosome segregation. Finally, unexpectedly SMC1B depletion impairs gene transcription, particularly at genes mapping to clusters such as HOX and PCDHB. Genome-wide analyses show that cluster genes changing in expression are enriched for cohesin-SMC1B binding. PMID- 26673122 TI - New Insights into the High-Density Lipoprotein Dilemma. AB - Although high-density lipoprotein-cholesterol (HDL-C) concentration is a negative risk factor for atherosclerotic cardiovascular disease (CVD), efforts to reduce CVD risk by raising HDL-C have not been uniformly successful. Many studies have shown that alcohol consumption, that increases plasma HDL-C concentration, reduces CVD incidence. However, recent genetic studies in large populations have not only removed HDL-C from the causal link between plasma HDL-C concentration and reduced CVD risk, but also suggest that the association is weak. We propose here that the cardioprotective effects of alcohol are mediated by the interaction of its terminal metabolite, acetate, with the adipocyte free fatty acid receptor 2 (FFAR2), which elicits a profound antilipolytic effect that may increase insulin sensitivity without necessarily raising plasma HDL-C concentration. PMID- 26673126 TI - Hip and Wrist Accelerometer Algorithms for Free-Living Behavior Classification. AB - PURPOSE: Accelerometers are a valuable tool for objective measurement of physical activity (PA). Wrist-worn devices may improve compliance over standard hip placement, but more research is needed to evaluate their validity for measuring PA in free-living settings. Traditional cut-point methods for accelerometers can be inaccurate and need testing in free living with wrist-worn devices. In this study, we developed and tested the performance of machine learning (ML) algorithms for classifying PA types from both hip and wrist accelerometer data. METHODS: Forty overweight or obese women (mean age = 55.2 +/- 15.3 yr; BMI = 32.0 +/- 3.7) wore two ActiGraph GT3X+ accelerometers (right hip, nondominant wrist; ActiGraph, Pensacola, FL) for seven free-living days. Wearable cameras captured ground truth activity labels. A classifier consisting of a random forest and hidden Markov model classified the accelerometer data into four activities (sitting, standing, walking/running, and riding in a vehicle). Free-living wrist and hip ML classifiers were compared with each other, with traditional accelerometer cut points, and with an algorithm developed in a laboratory setting. RESULTS: The ML classifier obtained average values of 89.4% and 84.6% balanced accuracy over the four activities using the hip and wrist accelerometer, respectively. In our data set with average values of 28.4 min of walking or running per day, the ML classifier predicted average values of 28.5 and 24.5 min of walking or running using the hip and wrist accelerometer, respectively. Intensity-based cut points and the laboratory algorithm significantly underestimated walking minutes. CONCLUSIONS: Our results demonstrate the superior performance of our PA-type classification algorithm, particularly in comparison with traditional cut points. Although the hip algorithm performed better, additional compliance achieved with wrist devices might justify using a slightly lower performing algorithm. PMID- 26673128 TI - Altering Pace Control and Pace Regulation: Attentional Focus Effects during Running. AB - PURPOSE: To date, there are no published studies directly comparing self controlled (SC) and externally controlled (EC) pace endurance tasks. However, previous research suggests pace control may impact on cognitive strategy use and effort perceptions. The primary aim of this study was to investigate the effects of manipulating perception of pace control on attentional focus, physiological, and psychological outcomes during running. The secondary aim was to determine the reproducibility of self-paced running performance when regulated by effort perceptions. METHODS: Twenty experienced endurance runners completed four 3-km time trials on a treadmill. Subjects completed two SC pace trials, one perceived exertion clamped (PE) trial, and one EC pace time trial. PE and EC were completed in a counterbalanced order. Pacing strategy for EC and perceived exertion instructions for PE replicated the subjects' fastest SC time trial. RESULTS: Subjects reported a greater focus on cognitive strategies such as relaxing and optimizing running action during EC than during SC. The mean HR was 2% lower during EC than that during SC despite an identical pacing strategy. Perceived exertion did not differ between the three conditions. However, increased internal sensory monitoring coincided with elevated effort perceptions in some subjects during EC and a 10% slower completion time for PE (13.0 +/- 1.6 min) than that for SC (11.8 +/- 1.2 min). CONCLUSIONS: Altering pace control and pace regulation impacted on attentional focus. External control over pacing may facilitate performance, particularly when runners engage attentional strategies conducive to improved running efficiency. However, regulating pace based on effort perceptions alone may result in excessive monitoring of bodily sensations and a slower running speed. Accordingly, attentional focus interventions may prove beneficial for some athletes to adopt task-appropriate attentional strategies to optimize performance. PMID- 26673127 TI - Decision Trees for Detection of Activity Intensity in Youth with Cerebral Palsy. AB - PURPOSE: To develop and test decision tree (DT) models to classify physical activity (PA) intensity from accelerometer output and Gross Motor Function Classification System (GMFCS) classification level in ambulatory youth with cerebral palsy (CP) and compare the classification accuracy of the new DT models to that achieved by previously published cut points for youth with CP. METHODS: Youth with CP (GMFCS levels I-III) (N = 51) completed seven activity trials with increasing PA intensity while wearing a portable metabolic system and ActiGraph GT3X accelerometers. DT models were used to identify vertical axis (VA) and vector magnitude (VM) count thresholds corresponding to sedentary (SED) (<1.5 METs), light-intensity PA (LPA) (>=1.5 and <3 METs) and moderate-to-vigorous PA (MVPA) (>=3 METs). Models were trained and cross-validated using the "rpart" and "caret" packages within R. RESULTS: For the VA (VA_DT) and VM DT (VM_DT), a single threshold differentiated LPA from SED, whereas the threshold for differentiating MVPA from LPA decreased as the level of impairment increased. The average cross-validation accuracies for the VC_DT were 81.1%, 76.7%, and 82.9% for GMFCS levels I, II, and III. The corresponding cross-validation accuracies for the VM_DT were 80.5%, 75.6%, and 84.2%. Within each GMFCS level, the DT models achieved better PA intensity recognition than previously published cut points. The accuracy differential was greatest among GMFCS level III participants, in whom the previously published cut points misclassified 40% of the MVPA activity trials. CONCLUSIONS: The GMFCS-specific cut points provide more accurate assessments of MVPA levels in youth with CP across the full spectrum of ambulatory ability. PMID- 26673129 TI - Performance of Activity Classification Algorithms in Free-Living Older Adults. AB - PURPOSE: The objective of this study is to compare activity type classification rates of machine learning algorithms trained on laboratory versus free-living accelerometer data in older adults. METHODS: Thirty-five older adults (21 females and 14 males, 70.8 +/- 4.9 yr) performed selected activities in the laboratory while wearing three ActiGraph GT3X+ activity monitors (in the dominant hip, wrist, and ankle; ActiGraph, LLC, Pensacola, FL). Monitors were initialized to collect raw acceleration data at a sampling rate of 80 Hz. Fifteen of the participants also wore GT3X+ in free-living settings and were directly observed for 2-3 h. Time- and frequency-domain features from acceleration signals of each monitor were used to train random forest (RF) and support vector machine (SVM) models to classify five activity types: sedentary, standing, household, locomotion, and recreational activities. All algorithms were trained on laboratory data (RFLab and SVMLab) and free-living data (RFFL and SVMFL) using 20 s signal sampling windows. Classification accuracy rates of both types of algorithms were tested on free-living data using a leave-one-out technique. RESULTS: Overall classification accuracy rates for the algorithms developed from laboratory data were between 49% (wrist) and 55% (ankle) for the SVMLab algorithms and 49% (wrist) to 54% (ankle) for the RFLab algorithms. The classification accuracy rates for SVMFL and RFFL algorithms ranged from 58% (wrist) to 69% (ankle) and from 61% (wrist) to 67% (ankle), respectively. CONCLUSIONS: Our algorithms developed on free-living accelerometer data were more accurate in classifying the activity type in free-living older adults than those on our algorithms developed on laboratory accelerometer data. Future studies should consider using free-living accelerometer data to train machine learning algorithms in older adults. PMID- 26673130 TI - Postexercise Hypotension after Heart Transplant: Water- versus Land-Based Exercise. AB - PURPOSE: Heart transplant recipients (HTx) have a high prevalence of hypertension. Although exercise training promotes blood pressure (BP) reduction in HTx, the effects of a single exercise bout are unknown. Thus, we analyzed the acute effects of heated water-based exercise (HEx) versus land-based exercise (LEx) on ambulatory BP (ABP) in HTx. METHODS: Eighteen (six females) clinically stable HTx (time since surgery = 5.0 +/- 0.7 yr) age 45.7 +/- 2.7 yr underwent 30 min of HEx (walking inside the pool), LEx (walking on a treadmill), and nonexercise control (CON) intervention in random order (2-5 d between interventions). HEx and LEx intensity was set at 11-13 in the 6-20 RPE scale. Twenty-four-hour (24-h) ABP monitoring was performed after each intervention. RESULTS: No significant differences between interventions were found in 24-h and nighttime BP. However, daytime diastolic BP was significantly lower after HEx than CON (-4 +/- 1.6 mm Hg, P = 0.03), and daytime diastolic BP tended to be lower after LEx than CON (-2.3 +/- 1.1 mm Hg, P = 0.052). Hourly analysis showed that systolic and diastolic BP values were lower after HEx (average reductions of 6.6 to 12.3 mm Hg, P < 0.01) and LEx (average reductions of 5 to 8.3 mm Hg, P < 0.05) than after CON in several hours. No significant differences between HEx and LEx were found in any ABP data. CONCLUSION: HEx and LEx promoted similar reductions in ABP of heart transplant recipients, which suggests that they may be a tool to counteract hypertension in this high-risk population. PMID- 26673131 TI - Binding mechanisms of 1,4-dihydropyridine derivatives to L-type calcium channel Cav1.2: a molecular modeling study. AB - L-type Ca(2+) channels (LTCCs), the heteromultimeric proteins, are associated with electrical signaling and provide the key link between electrical signals and non-electrical processes. 1,4-Dihydropyridine (DHP) derivatives are a major class of blockers for LTCCs, and have experienced widespread use in the treatment of cardiovascular diseases. However, the precise knowledge of the binding mechanism of these ligands to LTCCs at the atomic level has remained unknown because of the unavailability of the crystal structures of LTCCs. In this study, homology modeling, molecular docking, molecular dynamics (MD) simulations, free energy calculations and decomposition were employed to explore the structural requirement of the binding of DHP derivatives to human Cav1.2, a member of LTCCs. The binding conformations of the DHPs in the active site of Cav1.2 were predicted, and the rank of the binding free energies of Cav1.2/DHPs is generally consistent with the experimental data. The structural analysis shows that most studied ligands fit into a hydrophobic pocket formed by Phe1129, Ile1173, Phe1176, Met1177 and Met1509, and form aryl-aryl interaction with Phe1129 or Tyr1508. The consistency between the predictions and experimental data suggest that the developed model is reliable and can be used as a valuable platform for the structure-based design of new potent ligands of Cav1.2. PMID- 26673132 TI - Salmonella Virulence Factor SsrAB Regulated Factor Modulates Inflammatory Responses by Enhancing the Activation of NF-kappaB Signaling Pathway. AB - Effector proteins encoded by Salmonella pathogenicity islands play a key role in promoting bacterial intracellular survival, colonization, and pathogenesis. In this study, we investigated the function of the virulence-associated effector SrfA (SsrAB regulated factor) both in macrophages in vitro and in infected mice in vivo. SrfA was secreted into the cytoplasm during S. Typhimurium infection and disassociated IL-1R-associated kinase-1 (IRAK-1) from the IRAK-1-Toll interacting protein (Tollip) complex by interacting with Tollip. The released IRAK-1 was phosphorylated and subsequently activated the NF-kappaB signaling pathway, which enhanced the LPS-induced expression of inflammatory cytokines, such as IL-8, IL 1beta, and TNF-alpha. The coupling of ubiquitin to endoplasmic reticulum degradation aa 183-219 domain of Tollip is the binding region for SrfA, and both the MDaa207-226 and CTaa357-377 regions of SrfA mediate binding to Tollip and NF kappaB signaling activation. Deletion of SrfA in S. Typhimurium had no notable effects on its replication but impaired the induction of NF-kappaB activation in infected macrophages. The mice infected with srfA-deficient bacteria exhibited a decreased inflammatory response and an increased survival rate compared with those infected with wild-type S. Typhimurium. We conclude that SrfA is a novel Salmonella virulence effector that helps modulate host inflammatory responses by promoting NF-kappaB signaling activation. PMID- 26673133 TI - Cutting Edge: Role of NK Cells and Surfactant Protein D in Dendritic Cell Lymph Node Homing: Effects of Ozone Exposure. AB - The roles of NK cells, surfactant protein D (SP-D), and IFN-gamma, as well as the effect of ozone (O3) inhalation, were studied on recirculation of pulmonary dendritic cells (DC) to the mediastinal lymph nodes. O3 exposure and lack of SP-D reduced NK cell IFN-gamma and lung tissue CCL21 mRNA expression and impaired DC homing to the mediastinal lymph nodes. Notably, addition of recombinant SP-D to naive mononuclear cells stimulated IFN-gamma release in vitro. Because NKp46, a glycosylated membrane receptor, was necessary for dose-dependent SP-D binding to NK cells in vitro and DC migration in vivo, we speculate that SP-D may constitutively stimulate IFN-gamma production by NK cells, possibly via NKp46. This mechanism could then initiate the IFN-gamma/IL-12 feedback circuit, a key amplifier of DC lymph node homing. Inhibition of this process during an acute inflammatory response causes DC retention in the peripheral lung tissue and contributes to injury. PMID- 26673134 TI - Cutting Edge: Ezrin Regulates Inflammation by Limiting B Cell IL-10 Production. AB - IL-10 produced by B cells is important for controlling inflammation, thus underscoring the need to identify mechanisms regulating its production. In this study, we demonstrate that conditional deletion of ezrin in B cells increases IL 10 production induced by TLR4 ligation. The MyD88-independent Toll/IL-1R domain containing adapter inducing IFN-beta-IFN regulatory factor 3 pathway is required for Ezrin-deficient B cells to produce higher IL-10 upon LPS stimulation. Treatment of B cells with a novel small-molecule inhibitor of ezrin induces its dephosphorylation and increases LPS-induced NF-kappaB and IFN regulatory factor 3 activation and IL-10 secretion, indicating a role for threonine 567 phosphorylation of ezrin in limiting IL-10. Loss of ezrin in B cells results in dampened proinflammatory response to a sublethal dose of LPS in vivo, which is dependent on increased IL-10 production. Taken together, our data yield new insights into molecular and membrane-cytoskeletal regulation of B cell IL-10 production and reveal ezrin as a potential therapeutic target in inflammatory diseases. PMID- 26673136 TI - Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection. AB - Although Streptococcus pneumoniae is usually found as a commensal in healthy individuals, it can act as a pathogen in trauma patients, causing such complications as early-onset pneumonia and sepsis. We discovered that treating mice with an A-class CpG-oligodeoxynucleotide (ODN) at 2 h after traumatic injury significantly improved mouse survival following early-onset secondary lung infection with S. pneumoniae. This study used mass cytometry (cytometry by time of-flight) and Luminex technologies to characterize the cellular immune response to secondary S. pneumoniae lung infection at 1 and 3 d postinfection. We found increased expression of CD14, CD64, and PD-L1 on F4-80(+) and F4-80(+)CD11c(+) macrophages, CD11c(+) dendritic cells, and CD14(+)CD172a(+) cells after burn injury and infection, supporting previous reports of innate immune cell activation in sepsis. CpG-ODN treatment at 2 h after burn-injury reversed these effects; improved pathogen clearance; and led to an increased expression of CD25, CD27, MHCII, and IL-17 on or in TCRgammadelta cells at 1 d postinfection. At 3 d postinfection, CpG-ODN treatment increased the expression of PD-L1 on innate cell subsets. Furthermore, we analyzed cytokine levels in lung-washout samples of TCRgammadelta cell-depleted (TCRgammadelta(-)) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRgammadelta cells. In summary, we demonstrate that cytometry by time-of-flight provides an effective strategy to systematically identify specific cellular phenotypic responses to trauma and bacterial pneumonia and to discover changes in immune system phenotypes associated with beneficial immunotherapy. PMID- 26673135 TI - Selective ORAI1 Inhibition Ameliorates Autoimmune Central Nervous System Inflammation by Suppressing Effector but Not Regulatory T Cell Function. AB - The function of CD4(+) T cells is dependent on Ca(2+) influx through Ca(2+) release-activated Ca(2+) (CRAC) channels formed by ORAI proteins. To investigate the role of ORAI1 in proinflammatory Th1 and Th17 cells and autoimmune diseases, we genetically and pharmacologically modulated ORAI1 function. Immunization of mice lacking Orai1 in T cells with MOG peptide resulted in attenuated severity of experimental autoimmune encephalomyelitis (EAE). The numbers of T cells and innate immune cells in the CNS of ORAI1-deficient animals were strongly reduced along with almost completely abolished production of IL-17A, IFN-gamma, and GM CSF despite only partially reduced Ca(2+) influx. In Th1 and Th17 cells differentiated in vitro, ORAI1 was required for cytokine production but not the expression of Th1- and Th17-specific transcription factors T-bet and RORgammat. The differentiation and function of induced regulatory T cells, by contrast, was independent of ORAI1. Importantly, induced genetic deletion of Orai1 in adoptively transferred, MOG-specific T cells was able to halt EAE progression after disease onset. Likewise, treatment of wild-type mice with a selective CRAC channel inhibitor after EAE onset ameliorated disease. Genetic deletion of Orai1 and pharmacological ORAI1 inhibition reduced the leukocyte numbers in the CNS and attenuated Th1/Th17 cell-mediated cytokine production. In human CD4(+) T cells, CRAC channel inhibition reduced the expression of IL-17A, IFN-gamma, and other cytokines in a dose-dependent manner. Taken together, these findings support the conclusion that Th1 and Th17 cell function is particularly dependent on CRAC channels, which could be exploited as a therapeutic approach to T cell-mediated autoimmune diseases. PMID- 26673137 TI - MASP-1 and MASP-2 Do Not Activate Pro-Factor D in Resting Human Blood, whereas MASP-3 Is a Potential Activator: Kinetic Analysis Involving Specific MASP-1 and MASP-2 Inhibitors. AB - It had been thought that complement factor D (FD) is activated at the site of synthesis, and only FD lacking a propeptide is present in blood. The serum of mannose-binding lectin-associated serine protease (MASP)-1/3(-/-) mice contains pro-FD and has markedly reduced alternative pathway activity. It was suggested that MASP-1 and MASP-3 directly activate pro-FD; however, other experiments contradicted this view. We decided to clarify the involvement of MASPs in pro-FD activation in normal, as opposed to deficient, human plasma and serum. Human pro FD containing an APPRGR propeptide was produced in insect cells. We measured its activation kinetics using purified active MASP-1, MASP-2, MASP-3, as well as thrombin. We found all these enzymes to be efficient activators, whereas MASP proenzymes lacked such activity. Pro-FD cleavage in serum or plasma was quantified by a novel assay using fluorescently labeled pro-FD. Labeled pro-FD was processed with t1/2s of ~ 3 and 5 h in serum and plasma, respectively, showing that proteolytic activity capable of activating pro-FD exists in blood even in the absence of active coagulation enzymes. Our previously developed selective MASP-1 and MASP-2 inhibitors did not reduce pro-FD activation at reasonable concentration. In contrast, at very high concentration, the MASP-2 inhibitor, which is also a poor MASP-3 inhibitor, slowed down the activation. When recombinant MASPs were added to plasma, only MASP-3 could reduce the half life of pro-FD. Combining our quantitative data, MASP-1 and MASP-2 can be ruled out as direct pro-FD activators in resting blood; however, active MASP-3 is a very likely physiological activator. PMID- 26673138 TI - The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination. AB - Human colorectal cancer (CRC) is a frequent neoplasia in Western countries, and its metastatic progression is a major cause of cancer-related death. In search of specific molecules upregulated in CRC, with possible clinical relevance, we performed a differential gene-profiling analysis in surgery-derived CRC samples and adjacent uninvolved intestinal mucosa. The chemokine CX3CL1 and its specific receptor CX3CR1 were significantly upregulated in tumors. Higher expression of CX3CL1 and CX3CR1 was confirmed by immunohistochemistry in 100 CRC tumor samples (stages I-III). Unexpectedly, high immune scores of CX3CL1 did not correlate with the density of tumor-infiltrating CD3(+) T cells or CD68(+) macrophages. Coexpression of ligand and receptor by tumor cells (axis-positive tumors) significantly associated with longer disease-free (p = 0.01) and disease-specific survival (p = 0.001). Conversely, axis-negative tumors (with low expression of both ligand and receptor) had increased risk of tumor relapse (p = 0.02), and increased likelihood of metachronous metastasis (p = 0.001), including after stage adjustment (p = 0.006). Transduction of CX3CL1 and CX3CR1 in CRC tumor cell lines induced cell aggregation that strongly inhibited in vitro migration in chemotaxis assays. In a mouse model of spleen-liver metastases, cancer dissemination to liver was dramatically reduced in CX3CL1-CX3CR1-expressing tumors, and ligand-receptor interaction was confirmed in cancer cells in vivo by fluorescence resonance energy transfer analysis. In conclusion, tumoral expression of the CX3CL1-CX3CR1 chemokine axis functions as a retention factor, increasing homotypic cell adhesion and limiting tumor spreading to metastatic sites. Lack or low levels of expression of CX3CL1-CX3CR1 by tumor cells identifies a group of CRC patients at increased risk of metastatic progression. PMID- 26673139 TI - TRPV4-Mediated Detection of Hyposmotic Stress by Skin Keratinocytes Activates Developmental Immunity. AB - As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos. Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms. This occurred through a transient potential receptor vanilloid 4/Ca(2+)/TGF-beta-activated kinase 1/NF-kappaB signaling pathway. Surprisingly, the genes encoding antimicrobial effectors, which do not have the potential to cause tissue damage, are constitutively expressed during development, independently of both commensal microbes and osmotic stress. Our results reveal that osmotic stress is associated with the induction of developmental immunity in the absence of tissue damage and point out to the embryo skin as the first organ with full capacities to mount an innate immune response. PMID- 26673140 TI - Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia. AB - Epidemiologic studies in humans have demonstrated that infection with helminth parasites is associated with a reduced risk of developing autoimmune diseases. Mechanistic studies in mice have linked the protective effect of helminths on autoimmunity to the suppressive activity of helminth-induced regulatory T cells (Tregs) or Th2 cells. In this study, we demonstrate that treatment of mice with Fasciola hepatica excretory-secretory products (FHES) attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Protection was associated with a significant reduction in the infiltration of pathogenic Th1 and Th17 cells into the brain. Although FHES enhanced anti-inflammatory cytokine and Th2 responses, protection against EAE was independent of IL-4, IL-10, and Tregs. However, administration of FHES induced production of the type 2 cytokines IL-33 and IL-5, which promoted accumulation of eosinophils. FHES-induced expansion of eosinophils and protection against EAE was lost in IL-33(-/-) mice and upon neutralization of IL-5. Furthermore, transfer of FHES-induced or IL-33-induced eosinophils conferred protection against EAE. In addition, treatment of mice with recombinant IL-33 attenuated autoimmunity, and this was dependent on IL-5. To our knowledge, this study is the first to report a role for helminth-induced IL-5 and IL-33 in protection against autoimmunity. PMID- 26673141 TI - Differential Responsiveness of Innate-like IL-17- and IFN-gamma-Producing gammadelta T Cells to Homeostatic Cytokines. AB - gammadelta T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing gammadelta T (gammadeltaT-17) and IFN-gamma-producing gammadelta T (gammadeltaT IFNgamma) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional gammadelta T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like gammadeltaT-17 and gammadeltaT-IFNgamma cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional gammadelta T cells, but they do not monopolize the same cytokine. gammadeltaT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. gammadeltaT-IFNgamma cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional gammadelta T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive alphabeta T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that gammadelta T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes. PMID- 26673143 TI - TNF Regulates Essential Alternative Complement Pathway Components and Impairs Activation of Protein C in Human Glomerular Endothelial Cells. AB - Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe renal injury secondary to an overactive alternative complement pathway (AP). aHUS episodes are often initiated or recur during inflammation. We investigated gene expression of the surface complement regulatory proteins (CD55, CD59, CD46, and CD141 [thrombomodulin]) and AP components in human glomerular microvascular endothelial cells (GMVECs) and in HUVECs, a frequently used investigational model of endothelial cells. Surface complement regulatory proteins were also quantified by flow cytometry. All experiments were done with and without exposure to IL-1beta or TNF. Without cytokine stimulation, we found that GMVECs had greater AP activation than did HUVECs. With TNF stimulation, THBD gene expression and corresponding CD141 surface presence in HUVECs and GMVECs were reduced, and gene expression of complement components C3 (C3) and factor B (CFB) was increased. Consequently, AP activation, measured by Ba production, was increased, and conversion of protein C (PC) to activated PC by CD141-bound thrombin was decreased, in GMVECs and HUVECs exposed to TNF. IL-1beta had similar, albeit lesser, effects on HUVEC gene expression, and it only slightly affected GMVEC gene expression. To our knowledge, this is the first detailed study of the expression/display of AP components and surface regulatory proteins in GMVECs with and without cytokine stimulation. In aHUS patients with an underlying overactive AP, additional stimulation of the AP and inhibition of activated PC-mediated anticoagulation in GMVECs by the inflammatory cytokine TNF are likely to provoke episodes of renal failure. PMID- 26673142 TI - Mevalonate Biosynthesis Intermediates Are Key Regulators of Innate Immunity in Bovine Endometritis. AB - Metabolic changes can influence inflammatory responses to bacteria. To examine whether localized manipulation of the mevalonate pathway impacts innate immunity, we exploited a unique mucosal disease model, endometritis, where inflammation is a consequence of innate immunity. IL responses to pathogenic bacteria and LPS were modulated in bovine endometrial cell and organ cultures by small molecules that target the mevalonate pathway. Treatment with multiple statins, bisphosphonates, squalene synthase inhibitors, and small interfering RNA showed that inhibition of farnesyl-diphosphate farnesyl transferase (squalene synthase), but not 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyl diphosphate synthase, reduced endometrial organ and cellular inflammatory responses to pathogenic bacteria and LPS. Although manipulation of the mevalonate pathway reduced cellular cholesterol, impacts on inflammation were independent of cholesterol concentration as cholesterol depletion using cyclodextrins did not alter inflammatory responses. Treatment with the isoprenoid mevalonate pathway intermediates, farnesyl diphosphate and geranylgeranyl diphosphate, also reduced endometrial cellular inflammatory responses to LPS. These data imply that manipulating the mevalonate pathway regulates innate immunity within the endometrium, and that isoprenoids are regulatory molecules in this process, knowledge that could be exploited for novel therapeutic strategies. PMID- 26673144 TI - Dynamic Regulation of Tandem 3' Untranslated Regions in Zebrafish Spleen Cells during Immune Response. AB - Alternative polyadenylation (APA) has been found to be involved in tumorigenesis, development, and cell differentiation, as well as in the activation of several subsets of immune cells in vitro. Whether APA takes place in immune responses in vivo is largely unknown. We profiled the variation in tandem 3' untranslated regions (UTRs) in pathogen-challenged zebrafish and identified hundreds of APA genes with ~ 10% being immune response genes. The detected immune response APA genes were enriched in TLR signaling, apoptosis, and JAK-STAT signaling pathways. A greater number of microRNA target sites and AU-rich elements were found in the extended 3' UTRs than in the common 3' UTRs of these APA genes. Further analysis suggested that microRNA and AU-rich element-mediated posttranscriptional regulation plays an important role in modulating the expression of APA genes. These results indicate that APA is extensively involved in immune responses in vivo, and it may be a potential new paradigm for immune regulation. PMID- 26673146 TI - Exploring the effect of the Ln(III)/Ln(II) redox potential on C-F activation and on oxidation of some lanthanoid organoamides. AB - The divalent europium complexes, and (L(Me/Et) = p-HC6F4N(CH2)2NMe2/Et2), have been prepared from redox-transmetallation/protolysis (RTP) reactions between Eu metal, Hg(C6F5)2 and L(Me/Et)H in thf. The complexes exhibit close (C)F-Ln interactions and the amide ligands feature tridentate N,N',F chelation. The complexes are thermally robust but on exposure to light they undergo C-F activation. From exposure of to light, the Eu(III) mixed fluoride/oxide cluster, was isolated, but other well-defined C-F activation products have proven elusive due to the stability of Eu(II). Oxidation of [Ln(L(R))2(thf)2] (Ln = Eu, R = Me; Ln = Yb, R = Et) with I2 afforded the heteroleptic iodo complexes, [Ln(L(R))2I(thf)n] (Ln = Eu, n = 1; Ln = Yb, n = 0), and the homoleptic complexes, [Ln(L(R))3]. The formation of the iodo complexes and the heteroleptic complexes appear to occur by different routes. shows interesting structural differences from reported [Ln(L(Et))3] (Ln = La, Ce, Nd) complexes, and highlights an incomplete shift towards N,N' chelation to the much smaller Yb ion. was prepared from a protolysis reaction between [Sm(CH2C6H4-NMe2-o)3] and L(Me)H. Heating a solution of in toluene at 110 degrees C for three days did not afford any samarium fluoride complex. An RTP reaction with Sm afforded the heteroleptic samarium complex, , in very low yield. From an attempted protolysis reaction between [Sm(DippForm)2(thf)2] and L(Me)H, the mixed ligand samarium fluoride complex, , was isolated. Overall, the instability of Sm(II) precludes control over the C-F activation reactions. PMID- 26673145 TI - Coexpressed Catalase Protects Chimeric Antigen Receptor-Redirected T Cells as well as Bystander Cells from Oxidative Stress-Induced Loss of Antitumor Activity. AB - Treatment of cancer patients by adoptive T cell therapy has yielded promising results. In solid tumors, however, T cells encounter a hostile environment, in particular with increased inflammatory activity as a hallmark of the tumor milieu that goes along with abundant reactive oxygen species (ROS) that substantially impair antitumor activity. We present a strategy to render antitumor T cells more resilient toward ROS by coexpressing catalase along with a tumor specific chimeric Ag receptor (CAR) to increase their antioxidative capacity by metabolizing H2O2. In fact, T cells engineered with a bicistronic vector that concurrently expresses catalase, along with the CAR coexpressing catalase (CAR CAT), performed superior over CAR T cells as they showed increased levels of intracellular catalase and had a reduced oxidative state with less ROS accumulation in both the basal state and upon activation while maintaining their antitumor activity despite high H2O2 levels. Moreover, CAR-CAT T cells exerted a substantial bystander protection of nontransfected immune effector cells as measured by CD3zeta chain expression in bystander T cells even in the presence of high H2O2 concentrations. Bystander NK cells, otherwise ROS sensitive, efficiently eliminate their K562 target cells under H2O2-induced oxidative stress when admixed with CAR-CAT T cells. This approach represents a novel means for protecting tumor-infiltrating cells from tumor-associated oxidative stress mediated repression. PMID- 26673147 TI - Versatile process for the stereodiverse construction of 1,3-polyols: iterative chain elongation with chiral building blocks. AB - A versatile process for the construction of 1,3-polyols, a key structural element of polyketide-type natural products, is presented. The modular synthesis strategy involves the iterative chain elongation with novel four-carbon building blocks to access all possible stereoisomers of a growing 1,3-polyol chain. These chiral building blocks are designed to install four carbon atoms with two stereogenic centres by performing only four experimentally simple steps per elongation cycle, thus making these building blocks attractive for the realization of a universal platform from which to access a diverse range of polyketidic molecules. PMID- 26673148 TI - Heterotopic pregnancy. A case report. AB - Heterotopic pregnancy is the coexistence of living or dead intrauterine pregnancy, single or multiple, and extrauterine pregnancy located in the oviduct, ovary, uterine corner, cervix or peritoneal cavity. This condition is very rare (1:30 000 pregnancies). Nevertheless, in the latter years because of the development and accessibility of assisted reproductive techniques, the incidence of heterotopic pregnancies increased to 1:100 of pregnancies. The aim of this report is to present a case of early recognized intrauterine and extrauterine pregnancy. The case refers to 25-year-old patient, pregnant for the second time, in more or less 6th week of gestation, who had not been stated any heterotopic pregnancy incidence risk factors. After the observation lasting for several days in the Clinic, the presence of a living intrauterine and coexisting extrauterine pregnancy located in the right oviduct was stated. The patient had her right oviduct removed by means of laparoscopy. After the surgery the patient with the living intrauterine pregnancy was released from the Clinic. Normal further course of intrauterine pregnancy. The patient gave birth around her expected delivery date. The presented case indicates the significance of correctly and carefully performed ultrasound examination. Moreover, it is a warning for the doctors performing ultrasound examinations in the early weeks of pregnancy - the visualization of a normal pregnancy in the ultrasound examination does not release the examiner from a necessity of precise imaging of adnexa of the uterus. Early diagnosis of this pathology, thanks to a precise ultrasound examination, decreases the risk of complication incidence as well as women mortality. PMID- 26673149 TI - Genetic variation and association mapping for 12 agronomic traits in indica rice. AB - BACKGROUND: Increasing rice (Oryza sativa L.) yield is a crucial challenge for modern agriculture. The ideal plant architecture is considered to be critical to enhance rice yield. Elite plant morphological traits should include compact plant type, short stature, few unproductive tillers, thick and sturdy stems and erect leaves. To reveal the genetic variations of important morphological traits, 523 germplasm accessions were genotyped using the Illumina custom-designed array containing 5,291 single nucleotide polymorphisms (SNPs) and phenotyped in two independent environments. Genome-wide association studies were performed to uncover the genotypic and phenotypic variations using a mixed linear model. RESULTS: In total, 126 and 172 significant loci were identified and these loci explained an average of 34.45% and 39.09% of the phenotypic variance in two environments, respectively, and 16 of 298 (~5.37%) loci were detected across the two environments. For the 16 loci, 423 candidate genes were predicted in a 200-kb region (+/-100 kb of the peak SNP). Expression-level analyses identified four candidate genes as the most promising regulators of tiller angle. Known (NAL1 and Rc) and new significant loci showed pleiotropy and gene linkage. In addition, a long genome region covering ~1.6 Mb on chromosome 11 was identified, which may be critical for rice leaf architecture because of a high association with flag leaf length and the ratio of flag leaf length and width. The pyramid effect of the elite alleles indicated that these significant loci could be beneficial for rice plant architecture improvements in the future. Finally, 37 elite varieties were chosen as breeding donors for further rice plant architectural modifications. CONCLUSIONS: This study detected multiple novel loci and candidate genes related to rice morphological traits, and the work demonstrated that genome-wide association studies are powerful strategies for uncovering the genetic variations of complex traits and identifying candidate genes in rice, even though the linkage disequilibrium decayed slowly in self-pollinating species. Future research will focus on the biological validation of the candidate genes, and elite varieties will also be of interest in genome selection and breeding by design. PMID- 26673151 TI - Positivity of both plasma Epstein-Barr virus DNA and serum Epstein-Barr virus capsid specific immunoglobulin A is a better prognostic biomarker for nasopharyngeal carcinoma. AB - BACKGROUND: Positivity of plasma Epstein-Barr virus (EBV)-DNA or serum virus capsid antigen-specific IgA (VCA-IgA) is a biomarker for the prognosis of nasopharyngeal carcinoma (NPC). The objective of this study was to determine the value of positivity for plasma EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC. METHODS: Plasma EBV-DNA and serum VCA-IgA in 506 NPC patients in this retrospective study were detected by quantitative real time polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. The value of positivity for EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC was analyzed. RESULTS: Patients with positivity for both EBV DNA and VCA-IgA had significantly shorter periods of relapse free survival (RFS) and overall survival (OS) than those with positive single measure or negative for both measures, and patients with positive single measure had significantly shorter periods of RFS and OS than those with negative for both. Multivariate analysis indicated that the positivity for EBV-DNA and/or VCA-IgA were significant risk factors for shorter periods of RFS and OS. CONCLUSION: These data indicated that positivity for both EBV-DNA and VCA-IgA was a better biomarker for the prognosis of patients with NPC. Our findings may provide new references for clinical practice. PMID- 26673150 TI - Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. AB - BACKGROUND: Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. RESULTS: We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. CONCLUSIONS: Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk. PMID- 26673152 TI - Functional tooth restoration utilising split germs through re-regionalisation of the tooth-forming field. AB - The tooth is an ectodermal organ that arises from a tooth germ under the regulation of reciprocal epithelial-mesenchymal interactions. Tooth morphogenesis occurs in the tooth-forming field as a result of reaction-diffusion waves of specific gene expression patterns. Here, we developed a novel mechanical ligation method for splitting tooth germs to artificially regulate the molecules that control tooth morphology. The split tooth germs successfully developed into multiple correct teeth through the re-regionalisation of the tooth-forming field, which is regulated by reaction-diffusion waves in response to mechanical force. Furthermore, split teeth erupted into the oral cavity and restored physiological tooth function, including mastication, periodontal ligament function and responsiveness to noxious stimuli. Thus, this study presents a novel tooth regenerative technology based on split tooth germs and the re-regionalisation of the tooth-forming field by artificial mechanical force. PMID- 26673154 TI - New media and critical care ultrasound. AB - The paper discusses the issue of spreading medical knowledge, connected particularly with ultrasonography, by the social media. Such a way of sharing knowledge and experience results from the needs of recipients - physicians who daily have limited free time. The paper presents the phenomenon of the free open access medical education (FOAM) along with its genesis, an open and global nature as well as the main communication channels. It is emphasized that education via the social media is becoming an element of the mainstream medical didactics. The aforementioned phenomenon is depicted in greater detail in the context of emergency ultrasonography. US imaging is one of the more popular issues in the FOAM community. The paper focuses on the Ultrasound Podcast and the initiative associated with it. Our native (Polish) project, CriticalUSG, is also presented together with its numerous editions. Apart from these two projects, other initiatives, which are equally important not only due to ultrasonography, are also briefly mentioned. The aim of the paper is to interest the reader with the FOAM phenomenon as an open access, free and global medical discussion. PMID- 26673153 TI - Metabolomic analysis with GC-MS to reveal potential metabolites and biological pathways involved in Pb &Cd stress response of radish roots. AB - The radish (Raphanus sativus L.) is an important root vegetable crop. In this study, the metabolite profiling analysis of radish roots exposed to lead (Pb) and cadmium (Cd) stresses has been performed using gas chromatography-mass spectrometry (GC-MS). The score plots of principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) showed clear discrimination between control and Pb- or Cd-treated samples. The metabolic profiling indicated Pb or Cd stress could cause large metabolite alteration mainly on sugars, amino acids and organic acids. Furthermore, an integrated analysis of the effects of Pb or Cd stress was performed on the levels of metabolites and gene transcripts from our previous transcriptome work in radish roots. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of integration data demonstrated that exposure of radish to Pb stress resulted in profound biochemical changes including carbohydrate metabolism, energy metabolism and glutathione metabolism, while the treatment of Cd stress caused significant variations in energy production, amino acid metabolism and oxidative phosphorylation-related pathways. These results would facilitate further dissection of the mechanisms of heavy metal (HM) accumulation/tolerance in plants and the effective management of HM contamination in vegetable crops by genetic manipulation. PMID- 26673155 TI - Collagen fragment biomarkers as serological biomarkers of lean body mass - a biomarker pilot study from the DAHANCA25B cohort and matched controls. AB - BACKGROUND: Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying success. Easily applicable serological biomarkers of lean and/or muscle mass and change therein would benefit monitoring of muscle mass during muscle atrophy as well as during recovery. We set out to validate if novel peptide biomarkers derived from Collagen III and VI were markers of lean body mass (LBM) or change therein in head and neck cancer patients in the Danish Head and Neck Cancer Group(DAHANCA) 25B cohort subjected to resistance training as well as in an age-matched and gender-matched control group. METHODS: Blood samples and dual X-ray absorptiometry data were measured at baseline, after 12 and 24 weeks in 41 HNSCC subjects of the DAHANCA 25B cohort of subjects recovering from neck and head cancer (stages provided in Table 1), and at baseline only in 21 healthy age matched and gender-matched controls. Serum from blood was analyzed for the ProC3, IC6, and C6M peptide biomarkers and LBM were derived from the dual X-ray absorptiometry scans. RESULTS: We were not able to show any correlation between biomarkers and LBM or C6M and anabolic response to exercise in recovering head and neck cancer patients. However, we did find that the biomarkers IC6, IC6/C6M, and ProC3 are biomarkers of LBM in the control group subjects (R (2)/P of 0.249/0.035, 0.416/0.007 and 0.178 and P = 0.057, respectively). CONCLUSION: In conclusion, the IC6, ProC3, and IC6/C6M biomarkers are indeed biomarkers of LBM in healthy individuals of both genders, but not in HNSCC patients. PMID- 26673156 TI - Exploring the Potential of Laser Ablation Carbon Isotope Analysis for Examining Ecology during the Ontogeny of Middle Pleistocene Hominins from Sima de los Huesos (Northern Spain). AB - Laser ablation of tooth enamel was used to analyze stable carbon isotope compositions of teeth of hominins, red deer, and bears from middle Pleistocene sites in the Sierra de Atapuerca in northern Spain, to investigate the possibility that this technique could be used as an additional tool to identify periods of physiological change that are not detectable as changes in tooth morphology. Most of the specimens were found to have minimal intra-tooth variation in carbon isotopes (< 2.30/00), suggesting isotopically uniform diets through time and revealing no obvious periods of physiological change. However, one of the two sampled hominin teeth displayed a temporal carbon isotope shift (3.20/00) that was significantly greater than observed for co-occurring specimens. The delta13C value of this individual averaged about -160/00 early in life, and -130/00 later in life. This isotopic change occurred on the canine crown about 4.2 mm from the root, which corresponds to an approximate age of two to four years old in modern humans. Our dataset is perforce small owing to the precious nature of hominid teeth, but it demonstrates the potential utility of the intra-tooth isotope profile method for extracting ontogenetic histories of human ancestors. PMID- 26673157 TI - The value of intraoperative ultrasound in the recognition of pseudo-swelling of the spinal cord. AB - We present the case of a woman who presented with weakness of both legs due to a low grade tumor of the spinal cord. Excision of the tumor was performed and confirmed with intraoperative ultrasound. Prior to dural closure the spinal cord was found to be pushed dorsally with herniation of the cord through the dural defect. Intraoperative ultrasound showed a collection of cerebrospinal fluid in an anterior pocket giving the impression of the cord being swollen. Once cerebrospinal fluid was drained, the cord settled within the thecal space and closure of the dural defect was performed. Surgery for an intramedullary spinal cord tumor can cause a significant amount of swelling and either a duroplasty is required or the dura is left open with meticulous closure of the wound. Ultrasound is helpful to identify pathology anterior to the cord and prevents the potential complications associated with duroplasty or leaving the dura open. PMID- 26673158 TI - Standards of the Polish Ultrasound Society - update. Examination of extracranial carotid and vertebral arteries. AB - The role of a standard is to describe examination techniques, recommended norms as well as principles necessary to obtain results and draw appropriate conclusions, rather than a description of pathologies. The paper presents a technique for carotid artery examination as well as currently recommended standards. According to San Francisco Consensus from 2003, a significant stenosis of 70% may be detected when systolic velocity in the internal carotid artery stenosis is >230 cm/s, and the diastolic velocity is >100 cm/s. The common carotid artery velocity is also taken into account. Hemodynamic evaluation is therefore the primary method for the assessment of the degree of internal carotid artery stenosis. It is important that the examination is performed at an insonation angle of 60 degrees as measurements at higher angles result in an exponential increase in measurement error. Also, an extended version of standards involving measurements performed behind stenosis, which are used in some clinics, is included in the paper. The paper further presents guidelines for the description of the identified pathologies, which ensure that the findings prove unambiguous for clinicians, especially when stenosis eligible for surgical intervention is detected. Morphological measurement of stenosis (according to NASCET criteria) is only of supplementary character (confirming morphological grounds for the increase of velocity) and has no critical importance, especially due to high measurement divergence. Description of atherosclerotic plaques, especially hypoechoic ones, which are considered potentially unstable and may lead to a raised risk of stroke, is a very important element of examination. The paper is based on Standards of the Polish Ultrasound Society and updated based on the latest literature reports. PMID- 26673159 TI - Epithelial ovarian cancer stem-like cells expressing alpha-gal epitopes increase the immunogenicity of tumor associated antigens. AB - BACKGROUND: As ovarian cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and chemo-resistance, new stratagems that selectively target ovarian CSCs are critically significant. Our previous work have demonstrated that ovarian cancer spheroid cells are tumorigenic and chemo resistant, and have the properties of ovarian CSCs. Herein, we hypothesized that expressing alpha-gal epitopes on ovarian spheroid cells may help eliminate CSCs and improve the outcome of therapeutic intervention for ovarian cancer patients. METHODS: Lentivirus-mediated transfer of a pig alpha(1,3)galactosyltransferase [alpha1,3GT] enzyme gene into human ovarian cell line SKOV3 cells formed alpha gal epitope-expressing cells (SKOV3-gal cells), and then these cells were maintained in a serum-free culture system to form SKOV3-gal spheroid cells. Efficacy of this cell vaccine was demonstrated in alpha1,3GT knockout mice (alpha1,3GT KO mice). RESULTS: The antibody titers to alpha-gal epitopes measured by ELISA were significantly increased in alpha1,3GT KO mice after immunization with SKOV3-gal spheroid cells. Furthermore, compared with the non-immunized KO mice, the SKOV3 tumors grafted under renal capsules of KO mice immunized with SKOV3-gal spheroid cells grew slower and began to shrink on day 12. Western blot analysis also showed that immunized KO mice can produce effective antibody against certain tumor associated antigens (TAAs) derived from both SKOV3 cells and SKOV3 spheroid cells. The TAAs were further investigated by mass spectrometry and RNA interference (RNAi) technology. The results suggested that antibodies responding to protein c-erbB-2 may be raised in the sera of the mice after immunization with SKOV3-gal spheroid cells. Ultimately, vaccination with SKOV3 gal spheroid cells induced more CD3+CD4+T cells in the spleen of immunized mice than non-immunized KO mice. CONCLUSIONS: The results suggest that vaccination using ovarian cancer stem-like cells engineered to express alpha-gal epitopes may be a novel strategy for treatment of ovarian cancer. PMID- 26673161 TI - A New Sail-Backed Styracosternan (Dinosauria: Ornithopoda) from the Early Cretaceous of Morella, Spain. AB - A new styracosternan ornithopod genus and species is here described based on a partial postcranial skeleton and an associated dentary tooth of a single specimen from the Arcillas de Morella Formation (Early Cretaceous, late Barremian) at the Morella locality, (Castellon, Spain). Morelladon beltrani gen. et sp. nov. is diagnosed by eight autapomorphic features. The set of autapomorphies includes: very elongated and vertical neural spines of the dorsal vertebrae, midline keel on ventral surface of the second to fourth sacral vertebrae restricted to the anterior half of the centrum, a posterodorsally inclined medial ridge on the postacetabular process of the ilium that meets its dorsal margin and distal end of the straight ischial shaft laterally expanded, among others. Phylogenetic analyses reveal that the new Iberian form is more closely related to its synchronic and sympatric contemporary European taxa Iguanodon bernissartensis and Mantellisaurus atherfieldensis, known from Western Europe, than to other Early Cretaceous Iberian styracosternans (Delapparentia turolensis and Proa valdearinnoensis). The recognition of Morelladon beltrani gen. et sp. nov. indicates that the Iberian Peninsula was home to a highly diverse medium to large bodied styracosternan assemblage during the Early Cretaceous. PMID- 26673160 TI - Y-27632, a ROCK Inhibitor, Promoted Limbal Epithelial Cell Proliferation and Corneal Wound Healing. AB - Transplantation of ex vivo cultured limbal epithelial cells is proven effective in restoring limbal stem cell deficiency. The present study aimed to investigate the promoting effect of Y-27632 on limbal epithelial cell proliferation. Limbal explants isolated from human donor eyes were expanded three weeks on culture dishes and outgrowth of epithelial cells was subsequently subcultured for in vitro experiments. In the presence of Y-27632, the ex vivo limbal outgrowth was accelerated, particularly the cells with epithelial cell-like morphology. Y-27632 dose-dependently promoted the proliferation of in vitro cultured human limbal epithelial cells as examined by phase contrast microscopy and luminescent cell viability assay 30 hours after the treatment. The colony forming efficacy determined 7 days after the treatment was enhanced by Y-27632 also in a dose dependent manner. The number of p63- or Ki67-positive cells was dose-dependently increased in Y-27632-treated cultures as detected by immunofluorescent staining and western blotanalysis. Cell cycle analysis by flow cytometric method revealed an increase in S-phase proliferating cells. The epithelial woundclosure rate was shown to be faster in experimental group received topical treatment withY-27632 than the sham control using a rat corneal wounding model. These resultsdemonstrate that Y-27632 can promote both the ex vivo and in vitro proliferation oflimbal epithelial cell proliferation. The in vivo enhanced epithelial wound healingfurther implies that the Y-27632 may act as a new strategy for treating limbal stem cell deficiency. PMID- 26673162 TI - Cardiometabolic and vascular risks in young and adolescent girls with Turner syndrome. AB - BACKGROUND: Turner syndrome (TS) is the most common chromosomal abnormality in females and is associated with several co-morbidities. It commonly results from X monosomy which is diagnosed on a 30 cell karyotype. Congenital heart disease is a clinical feature in 30% of cases. It is becoming evident that TS patients have an increased risk of cardiovascular and cerebrovascular diseases. SCOPE OF REVIEW: This review provides a detailed overview of the literature surrounding cardiometabolic health in childhood and adolescent TS. In addition, the review also summarises the current data on the impact of growth hormone (GH) therapy on cardiometabolic risk in paediatric TS patients. MAJOR CONCLUSIONS: Current epidemiological evidence suggests that young women and girls with TS have unfavourable cardiometabolic risk factors which predispose them to adverse cardiac and cerebrovascular outcomes in young adulthood. It remains unclear whether this risk is the result of unidentified factors which are intrinsic to TS, or whether modifiable risk factors (obesity, hypertension, hyperglycaemia) are contributing to this risk. GENERAL SIGNIFICANCE: From a clinical perspective, this review highlights the importance of regular screening and pro-active management of cardiometabolic risk from childhood in TS cohorts and that future research should aim to address whether modification of these variables at a young age can alter the disease process and atherosclerotic outcomes in adulthood. PMID- 26673163 TI - Intra-Individual Variability of Surface Electromyography in Front Crawl Swimming. AB - The variability of electromyographic (EMG) recordings between and within participants is a complex problem, rarely studied in swimming. The importance of signal normalization has long been recognized, but the method used might influence variability. The aims of this study were to: (i) assess the intra individual variability of the EMG signal in highly skilled front crawl swimmers, (ii) determine the influence of two methods of both amplitude and time normalization of the EMG signal on intra-individual variability and of time normalization on muscle activity level and (iii) describe the muscle activity, normalized using MVIC, in relation to upper limb crawl stroke movements. Muscle activity of rectus abdominis and deltoideus medialis was recorded using wireless surface EMG in 15 adult male competitive swimmers during three trials of 12.5 m front crawl at maximal speed without breathing. Two full upper limb cycles were analyzed from each of the swimming trials, resulting in six full cycles used for the intra-individual variability assessment, quantified with the coefficient of variation (CV), coefficient of quartile variation (CQV) and the variance ratio (VR). The results of this study support previous findings on EMG patterns of deltoideus medialis and rectus abdominis as prime mover during the recovery (45% activity relative to MVIC), and stabilizer of the trunk during the pull (14.5% activity) respectively. The intra-individual variability was lower (VR of 0.34 0.47) when compared to other cyclic movements. No meaningful differences were found between variability measures CV or VR when applying either of the amplitude or the time normalization methods. In addition to reporting the mean amplitude and standard deviation, future EMG studies in swimming should also report the intra-individual variability, preferably using VR as it is independent of peak amplitude, provides a good measure of repeatability and is insensitive to mean EMG amplitude and the degree of smoothing applied. PMID- 26673164 TI - Correction: IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome. PMID- 26673165 TI - Population Estimation Methods for Free-Ranging Dogs: A Systematic Review. AB - The understanding of the structure of free-roaming dog populations is of extreme importance for the planning and monitoring of populational control strategies and animal welfare. The methods used to estimate the abundance of this group of dogs are more complex than the ones used with domiciled owned dogs. In this systematic review, we analyze the techniques and the results obtained in studies that seek to estimate the size of free-ranging dog populations. Twenty-six studies were reviewed regarding the quality of execution and their capacity to generate valid estimates. Seven of the eight publications that take a simple count of the animal population did not consider the different probabilities of animal detection; only one study used methods based on distances; twelve relied on capture-recapture models for closed populations without considering heterogeneities in capture probabilities; six studies applied their own methods with different potential and limitations. Potential sources of bias in the studies were related to the inadequate description or implementation of animal capturing or viewing procedures and to inadequacies in the identification and registration of dogs. Thus, there was a predominance of estimates with low validity. Abundance and density estimates carried high variability, and all studies identified a greater number of male dogs. We point to enhancements necessary for the implementation of future studies and to potential updates and revisions to the recommendations of the World Health Organization with respect to the estimation of free-ranging dog populations. PMID- 26673166 TI - The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults. AB - BACKGROUND: Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups. METHODS: Using a sample of 7276 respondents drawn from community centers, the REDISCOVER team gathered information on physical activity, CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, tobacco use) and socioeconomic and demographic variables in Malaysia. Because the study required medical examination, a convenience sampling frame was preferred in which all volunteers were included in the study. Fasting blood samples and anthropometric (height, weight and more) measurements were collected by trained staffs. Socio demographic and physical activity variables were recorded through questionnaires. A Chi-square test was performed to identify the bivariate association between the covariates (socioeconomic variables, demographic variables and physical activity) and outcome variable. The association between the main exposure, physical activity, and the outcome variable, cumulative CVD risk factors, was assessed using an ordinal logistic regression model, controlling for socioeconomic status and demographic influences in three different age groups, 35-49, 50-64 and 65 and above. RESULTS: The mean age of participants is 51.8 (SD = 9.4). Respondents in the age groups of 35-49 (aORmoderate = 0.12; 95 % CI: 0.02 - 0.53 ) and 65 and above (aORhigh = 0.58; 95 % CI: 0.24, 0.78) showed a statistically significant inverse relationship between physical activity and cumulative CVD risk factors. However, this relationship was not significant among respondents in the 50-64 age group suggesting the possible influence of other variables, such as stress and environment. CONCLUSIONS: The statistically significant results show a negative association between physical exercise and cumulative CVD risk factors. However, the lack of a significant relationship in the 50-64 age group suggests the need to include other considerations in future studies, such as stress and environment. PMID- 26673167 TI - Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling. AB - Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of alpha-smooth muscle actin, extracellular matrixprotein, transforming growth factor beta1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-alpha and interleukin 6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling. PMID- 26673169 TI - Mandibular Osteolytic Lesion Associated with Exuberant Hyaline Ring Granuloma Reaction. AB - OBJECTIVE: To report an unusual case of oral hyaline ring granuloma (HRG) that caused an extensive osteolytic lesion. CLINICAL PRESENTATION AND INTERVENTION: A 22-year-old female was referred to our hospital with a large expansile cystic lesion in the left mandibular ramus associated with a clinically visible, partially erupted third molar. A diagnosis of paradental cyst was made. After marsupialization of the lesion, histopathological analysis of the surgical specimen showed an unusual exuberant HRG reaction supported by scarce fibrous stroma. CONCLUSION: This was a case of exuberant HRG reaction that caused extensive bone destruction. PMID- 26673170 TI - The ghost of donor passed. PMID- 26673168 TI - Comparative transcriptomics reveals similarities and differences between astrocytoma grades. AB - BACKGROUND: Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic and epigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. METHODS: We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. RESULTS: Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth. We further found that PA I was significantly associated with the mesenchymal subtype typically observed for very aggressive GBM IV. Expression of endothelial and mesenchymal markers (ANGPT2, CHI3L1) indicated a stronger contribution of the micro-environment to the manifestation of the mesenchymal subtype than the tumor biology itself. We further inferred a transcriptional regulatory network associated with specific expression differences distinguishing PA I from AS II, AS III and GBM IV. Major central transcriptional regulators were involved in brain development, cell cycle control, proliferation, apoptosis, chromatin remodeling or DNA methylation. Many of these regulators showed directly underlying DNA methylation changes in PA I or gene copy number mutations in AS II, AS III and GBM IV. CONCLUSIONS: This computational study characterizes similarities and differences between all four astrocytoma grades confirming known and revealing novel insights into astrocytoma biology. Our findings represent a valuable resource for future computational and experimental studies. PMID- 26673171 TI - Revisiting the Anatomy of the Living Heart. AB - An understanding of the complexity of cardiac anatomy is required by all who seek, in the setting of cardiac disease, to interpret the images confronting them. Although the mysteries of cardiac structure have been extensively addressed, significant gaps continue to exist between the descriptions provided by morphologists and by those working in the clinical setting. In part, this reflects the limitations in providing 3D visualization of such a complicated organ. Current 3D imaging technology now permits visualization of the cardiac components using datasets obtained in the living individual. These advances, furthermore, demonstrate the anatomy in the setting of the heart as imaged within the thorax. It has been failure to describe the heart as it lies within the thorax that remains a major deficiency of many morphologists relying on the dissecting room to provide the gold standard. Describing the heart in attitudinally appropriate fashion, a basic rule of clinical anatomy, creates the necessary bridges between anatomists and clinicians. The rapid progression of cardiac interventional techniques, furthermore, emphasizes the need to revisit cardiac anatomy using a multidisciplinary approach. In this review, therefore, we illustrate the advantages of an attitudinally correct approach to cardiac anatomy. We then focus on the morphology of the arterial roots, revealing the accuracy that can now be achieved by clinicians using datasets obtained during life. PMID- 26673172 TI - Health Sector Evolution Plan in Iran; Equity and Sustainability Concerns. AB - In 2014, a series of reforms, called as the Health Sector Evolution Plan (HSEP), was launched in the health system of Iran in a stepwise process. HSEP was mainly based on the fifth 5-year health development national strategies (2011-2016). It included different interventions to: increase population coverage of basic health insurance, increase quality of care in the Ministry of Health and Medical Education (MoHME) affiliated hospitals, reduce out-of-pocket (OOP) payments for inpatient services, increase quality of primary healthcare, launch updated relative value units (RVUs) of clinical services, and update tariffs to more realistic values. The reforms resulted in extensive social reaction and different professional feedback. The official monitoring program shows general public satisfaction. However, there are some concerns for sustainability of the programs and equity of financing. Securing financial sources and fairness of the financial contribution to the new programs are the main concerns of policy-makers. Healthcare providers' concerns (as powerful and influential stakeholders) potentially threat the sustainability and efficiency of HSEP. Previous experiences on extending health insurance coverage show that they can lead to a regressive healthcare financing and threat financial equity. To secure financial sources and to increase fairness, the contributions of people to new interventions should be progressive by their income and wealth. A specific progressive tax would be the best source, however, since it is not immediately feasible, a stepwise increase in the progressivity of financing must be followed. Technical concerns of healthcare providers (such as nonplausible RVUs for specific procedures or nonefficient insurance-provider processes) should be addressed through proper revision(s) while nontechnical concerns (which are derived from conflicting interests) must be responded through clarification and providing transparent information. The requirements of HSEP and especially the key element of progressive tax should be considered properly in the coming sixth national development plan (2016-2021). PMID- 26673173 TI - Navigating Between Stealth Advocacy and Unconscious Dogmatism: The Challenge of Researching the Norms, Politics and Power of Global Health. AB - Global health research is essentially a normative undertaking: we use it to propose policies that ought to be implemented. To arrive at a normative conclusion in a logical way requires at least one normative premise, one that cannot be derived from empirical evidence alone. But there is no widely accepted normative premise for global health, and the actors with the power to set policies may use a different normative premise than the scholars that propose policies - which may explain the 'implementation gap' in global health. If global health scholars shy away from the normative debate - because it requires normative premises that cannot be derived from empirical evidence alone - they not only mislead each other, they also prevent and stymie debate on the role of the powerhouses of global health, their normative premises, and the rights and wrongs of these premises. The humanities and social sciences are better equipped and less reluctant - to approach the normative debate in a scientifically valid manner, and ought to be better integrated in the interdisciplinary research that global health research is, or should be. PMID- 26673174 TI - Validating and determining the weight of items used for evaluating clinical governance implementation based on analytic hierarchy process model. AB - BACKGROUND: The purpose of implementing a system such as Clinical Governance (CG) is to integrate, establish and globalize distinct policies in order to improve quality through increasing professional knowledge and the accountability of healthcare professional toward providing clinical excellence. Since CG is related to change, and change requires money and time, CG implementation has to be focused on priority areas that are in more dire need of change. The purpose of the present study was to validate and determine the significance of items used for evaluating CG implementation. METHODS: The present study was descriptive quantitative in method and design. Items used for evaluating CG implementation were first validated by the Delphi method and then compared with one another and ranked based on the Analytical Hierarchy Process (AHP) model. RESULTS: The items that were validated for evaluating CG implementation in Iran include performance evaluation, training and development, personnel motivation, clinical audit, clinical effectiveness, risk management, resource allocation, policies and strategies, external audit, information system management, research and development, CG structure, implementation prerequisites, the management of patients' non-medical needs, complaints and patients' participation in the treatment process. The most important items based on their degree of significance were training and development, performance evaluation, and risk management. The least important items included the management of patients' non-medical needs, patients' participation in the treatment process and research and development. CONCLUSION: The fundamental requirements of CG implementation included having an effective policy at national level, avoiding perfectionism, using the expertise and potentials of the entire country and the coordination of this model with other models of quality improvement such as accreditation and patient safety. PMID- 26673175 TI - Application of Quality Assurance Strategies in Diagnostics and Clinical Support Services in Iranian Hospitals. AB - BACKGROUND: Iran has a widespread diagnostics and clinical support services (DCSS) network that plays a crucial role in providing diagnostic and clinical support services to both inpatient and outpatient care. However, very little is known on the application of quality assurance (QA) policies in DCSS units. This study explores the extent of application of eleven QA strategies in DCSS units within Iranian hospitals and its association with hospital characteristics. METHODS: A descriptive cross-sectional study was conducted in 2009/2010. Data were collected from 554 DCSS units among 84 hospitals. RESULTS: The average reported application rate for the QA strategies ranged from 57%-94% in the DCSS units. Most frequently reported were checking drugs expiration dates (94%), pharmacopoeia availability (92%), equipment calibration (87%) and identifying responsibilities (86%). Least reported was external auditing of the DCSS (57%). The clinical chemistry and microbiology laboratories (84%), pharmacies, blood bank services (83%) reported highest average application rates across all questioned QA strategies. Lowest application rates were reported in human tissue banks (50%). There was no significant difference between the reported application rates in DCSS in the general/specialized, teaching/research, nonteaching/research hospitals with the exception of pharmacies and radiology departments. They reported availability of a written QA plan significantly more often in research hospitals. Nearly all QA strategies were reported to be applied significantly more often in the DCSS of Social Security Organization (SSO) and private-for profit hospitals than in governmental hospitals. CONCLUSION: There is still room for strengthening the managerial cycle of QA systems and accountability in the DCSS in Iranian hospitals. Getting feedback, change and learning through application of specific QA strategies (eg, external/internal audits) can be improved. Both the effectiveness of QA strategies in practice, and the application of these strategies in outpatient DCSS units require further policy attention. PMID- 26673176 TI - Are Sexual and Reproductive Health Policies Designed for All? Vulnerable Groups in Policy Documents of Four European Countries and Their Involvement in Policy Development. AB - BACKGROUND: Health policies are important instruments for improving population health. However, experience suggests that policies designed for the whole population do not always benefit the most vulnerable. Participation of vulnerable groups in the policy-making process provides an opportunity for them to influence decisions related to their health, and also to exercise their rights. This paper presents the findings from a study that explored how vulnerable groups and principles of human rights are incorporated into national sexual and reproductive health (SRH) policies of 4 selected countries (Spain, Scotland, Republic of Moldova, and Ukraine). It also aimed at discussing the involvement of vulnerable groups in SRH policy development from the perspective of policy-makers. METHODS: Literature review, health policy analysis and 5 semi-structured interviews with policy-makers were carried out in this study. Content analysis of SRH policies was performed using the EquiFrame analytical framework. RESULTS: The study revealed that vulnerable groups and core principles of human rights are differently addressed in SRH policies within 4 studied countries. The opinions of policy-makers on the importance of mentioning vulnerable groups in policy documents and the way they ought to be mentioned varied, but they agreed that a clear definition of vulnerability, practical examples, and evidences on health status of these groups have to be included. In addition, different approaches to vulnerable group's involvement in policy development were identified during the interviews and the range of obstacles to this process was discussed by respondents. CONCLUSION: Incorporation of vulnerable groups in the SRH policies and their involvement in policy development were found to be important in addressing SRH of these groups and providing an opportunity for them to advocate for equal access to healthcare and exercise their rights. Future research on this topic should include representatives of vulnerable communities which could help to build a dialogue and present the problem from multiple perspectives. PMID- 26673177 TI - Sustaining Health for Wealth: Perspectives for the Post-2015 Agenda: Comment on "Improving the World's Health Through the Post-2015 Development Agenda: Perspectives From Rwanda". AB - The sustainable development goals (SDGs) offer a unique opportunity for policy makers to build on the millennium development goals (MDGs) by adopting more sustainable approaches to addressing global development challenges. The delivery of health services is of particular concern. Most African countries are unlikely to achieve the health MDGs, however, significant progress has been made particularly in the area of child and maternal health due in part to significant external support. The weak global recovery, and persistent inequalities in access to healthcare, however, call into question the sustainability of the achievements made. Building on the principles articulated in Binagwaho and Scott, this commentary argues that addressing inequalities and promoting more integrated approaches to health service delivery is vital for consolidating and sustaining the health sector achievements in Africa. PMID- 26673178 TI - Why Good Quality Care Needs Philosophy More Than Compassion: Comment on "Why and How Is Compassion Necessary to Provide Good Quality Healthcare?". AB - Although Marianna Fotaki's Editorial is helpful and challenging by looking at both the professional and institutional requirements for reinstalling compassion in order to aim for good quality healthcare, the causes that hinder this development remain unexamined. In this commentary, 3 causes are discussed; the boundary between the moral and the political; Neoliberalism; and the underdevelopment of reflection on the nature of care. A plea is made for more philosophical reflection on the nature of care and its implications in healthcare education. PMID- 26673179 TI - Imagined in Policy, Inscribed on Bodies: Defending an Ethic of Compassion in a Political Context: Comment on "Why and How Is Compassion Necessary to Provide Good Quality Healthcare?". AB - In response to the International Journal of Health Policy and Management (IJHPM) editorial, this commentary adds to the debate about ethical dimensions of compassionate care in UK service provision. It acknowledges the importance of the original paper, and attempts to explore some of the issues that are raised in the context of nursing practice, research and education. It is argued that each of these fields of the profession are enacted in an escalating culture of corporatism, be that National Health Service (NHS) or university campus, and global neoliberalism. Post-structuralist ideas, notably those of Foucault, are borrowed to interrogate healthcare as discursive practice and disciplinary knowledge; where an understanding of the ways in which power and language operate is prominent. Historical and contemporary evidence of institutional and ideological degradation of sections of humanity, a 'history of the present,' serve as reminders of the import, and fragility, of ethical codes. PMID- 26673180 TI - "Horses for Courses": Comment on "Translating Evidence Into Healthcare Policy and Practice: Single Versus Multi-Faceted Implementation Strategies - Is There a Simple Answer to a Complex Question?". AB - This commentary considers the vexed question of whether or not we should be spending time and resources on using multifaceted interventions to undertake implementation of evidence in healthcare. A review of systematic reviews has suggested that simple interventions may be just as effective as those taking a multifaceted approach. Taking cognisance of the Promoting Action on Research Implementation in Health Services (PARIHS) framework this commentary takes account of the evidence, context and facilitation factors in undertaking implementation. It concludes that a 'horses for courses' approach is necessary meaning that the specific implementation approach should be selected to fit the implementation task in hand whether it be a single or multifaceted approach and reviewed on an individual basis. PMID- 26673181 TI - Wolves and Big Yellow Taxis: How Would Be Know If the NHS Is at Death's Door?: Comment on "Who killed the English National Health Service?". AB - Martin Powell suggests that the death of the English National Health Service (NHS) has been announced so many times we are at risk of not noticing should it actually happen. He is right. If we 'cry wolf' too many times, we risk losing sight of what is important about the NHS and why. PMID- 26673182 TI - Seriously Implementing Health Capacity Strengthening Programs in Africa: Comment on "Implementation of a Health Management Mentoring Program: Year-1 Evaluation of Its Impact on Health System Strengthening in Zambezia Province, Mozambique". AB - Faced with the challenges of healthcare reform, skills and new capabilities are needed to support the reform and it is of crucial importance in Africa where shortages affects the health system resilience. Edwards et al provides a good example of the challenge of implementing a mentoring program in one province in a sub-Saharan country. From this example, various aspects of strengthening the capacity of managers in healthcare are examined based on our experience in action training in Africa, as mentoring shares many characteristics with action training. What practical lessons can be drawn to promote the strengthening so that managers can better intervene in complex contexts? Deeper involvement of health authorities and more rigorous approaches are seriously desirable for the proper development of health capacity strengthening programs in Africa. PMID- 26673183 TI - Slow Poisoning? Interests, Emotions, and the Strength of the English NHS: Comment on "Who Killed the English National Health Service?". AB - Martin Powell makes the point that the death of the National Health Service (NHS) is constantly asserted without criteria. This article suggests that the NHS is many things, which makes criteria unstable. The alignment of interests in the structure of the NHS enables both overheated rhetoric and political strength, and that pluralization of provision might actually undermine that alignment over time. PMID- 26673184 TI - How Single Is "Single" - Some Pragmatic Reflections on Single Versus Multifaceted Interventions to Facilitate Implementation: Comment on "Translating Evidence Into Healthcare Policy and Practice: Single Versus Multifaceted Implementation Strategies - Is There a Simple Answer to a Complex Question?". AB - An earlier overview of systematic reviews and a subsequent editorial on single component versus multifaceted interventions to promote knowledge translation (KT) highlight complex issues in implementation science. In this supplemented commentary, further aspects are in focus; we propose examples from (KT) studies probing the issue of single interventions. A main point is that defining what is a single and what is a multifaceted intervention can be ambiguous, depending on how the intervention is conceived. Further, we suggest additional perspectives in terms of strategies to facilitate implementation. More specifically, we argue for a need to depict not only what activities are done in implementation interventions, but to unpack functions in particular contexts, in order to support the progress of implementation science. PMID- 26673185 TI - Unpacking "Health Reform" and "Policy Capacity": Comment on "Health Reform Requires Policy Capacity". AB - Health reform is the outcome of dispersed policy initiatives in different sectors, at different levels and across time. Policy work which can drive coherent health reform needs to operate across the governance structures as well as the institutions that comprise healthcare systems. Building policy capacity to support health reform calls for clarity regarding the nature of such policy work and the elements of policy capacity involved; and for evidence regarding effective strategies for capacity building. PMID- 26673186 TI - Policy Capacity Meets Politics: Comment on "Health Reform Requires Policy Capacity". AB - It is difficult to disagree with the general argument that successful health reform requires a significant degree of policy capacity or that all players in the policy game need to move beyond self-interested advocacy. However, an overly broad definition of policy capacity is a problem. More important perhaps, health reform inevitably requires not just policy capacity but political leadership and compromise. PMID- 26673187 TI - Cities and Health: A Response to the Recent Commentaries. PMID- 26673188 TI - Erratum: Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: Role in osteoclast-mediated NK cell activation. PMID- 26673189 TI - Simultaneous Determination of Menthol and Eucalyptol by the Densitometric HPTLC Method in Some External Analgesic Formulations. AB - Several analgesic pharmaceutical formulations dispensed for external use contain menthol and eucalyptol. Simultaneous determination of the two monoterpenes was achieved utilizing high-performance thin layer chromatography (HPTLC) densitometric analysis. The stationary phase composed of silica gel 60 F254 (E Merck, Germany) glass-backed plates coated with 0.2 mm layers. The used mobile phase hexane : ethyl acetate 8 : 2 (%, v/v) resulted in sharp, symmetrical and well-resolved peak at an Rf value of 0.34 +/- 0.04 and 0.56 +/- 0.04 for menthol and eucalyptol, respectively. Linearly range for menthol was 100-800 ng/spot (r(2) = 0.9979), whereas that for eucalyptol was 52.25-1107 ng/spot (r(2) = 0.9937). The developed method was validated following the International Conference on Harmonization guidelines. The method was found to be simple, accurate, time saving and enable analyses of many samples simultaneously. PMID- 26673190 TI - Two-Dimensional Micro-TLC Phenolic Fingerprints of Selected Mentha sp. on Cyano Bonded Polar Stationary Phase. AB - Micro-thin-layer chromatography in two-dimensional (2D-mTLC) mode in normal- (NP) and reversed-phase (RP) systems by use of cyanopropyl-bonded stationary phases was applied to make fingerprints of 11 species of Mentha genus and two finished pharmaceutical products. Non-aqueous eluents were used in the NP systems. Mixtures of acetonitrile with water and methanol with water were used in the RP chromatographic systems. Optimization of one-dimensional systems was performed by determining RM vs. composition of mobile phase dependencies for standards occurring in various Mentha sp. On the basis of these dependencies, the most selective chromatographic systems for each run were chosen. Then most selective eluents were applied to optimize two-dimensional systems by creating RF in NP systems vs. RF in RP systems correlations. The best two-dimensional systems were chosen on the basis of R(2) values for RF vs. RF correlations (the lowest values of R(2) coefficients). The 2D-mTLC optimized systems were applied to separate phenolic compounds and make fingerprints of the examined plant materials. PMID- 26673194 TI - Bilayer Deformation, Pores, and Micellation Induced by Oxidized Lipids. AB - The influence of different oxidized lipids on lipid bilayers was investigated with 16 individual 1 MUs atomistic molecular dynamics (MD) simulations. Binary mixtures of lipid bilayers of 1-palmitoyl-2-linoleoyl-sn-glycero-3 phosphatidylcholine (PLPC) and its peroxide and aldehyde products were performed at different concentrations. In addition, an asymmetrical short chain lipid, 1 palmitoyl-2-decanoyl-sn-glycero-3-phosphatidylcholine (PDPC), was used to compare the effects of polar/apolar groups in the lipid tail on lipid bilayer. Although water defects occurred with both aldehyde and peroxide lipids, full pore formation was observed only for aldehyde lipids. At medium concentrations the pores were stable. At higher concentrations, however, the pores became unstable and micellation occurred. Data analysis shows that aldehyde lipids' propensity for pore formation is due to their shorter and highly mobile tail. The highly polar peroxide lipids are stabilized by strong hydrogen bonds with interfacial water. PMID- 26673195 TI - Quantum-Classical Path Integral Simulation of Ferrocene-Ferrocenium Charge Transfer in Liquid Hexane. AB - We employ the quantum-classical path integral methodology to simulate the outer sphere charge-transfer process of the ferrocene-ferrocenium pair in liquid hexane with unprecedented accuracy. Comparison of the simulation results to those obtained by mapping the solvent on an effective harmonic bath demonstrates the accuracy of linear response theory in this system. PMID- 26673196 TI - Density Analysis of Intra- and Intermolecular Vibronic Couplings toward Bath Engineering for Singlet Fission. AB - Vibronic coupling plays a crucial role in singlet fission whereby a singlet exciton splits into two triplet excitons. In order to reveal the physicochemical origin of the vibronic coupling associated with singlet fission as well as to clarify its relationship with chemical structure, we evaluate relevant vibronic couplings from the viewpoint of their spatial contributions described by vibronic coupling density. From the analysis using a model tetracene dimer, a typical singlet fission system, the frequency dependence of vibronic couplings in each electronic state is found to be significantly different from that of another depending on the nature of the electronic structure (intra/intermolecular excitation) and the related vibrational motion. These findings contribute not only to the fundamental understanding of the singlet fission mechanism from the viewpoint of vibronic couplings but also to opening a new path to designing highly efficient singlet fission materials through phonon-bath engineering. PMID- 26673197 TI - Kinetic Analysis of H(+)-Na(+) Selectivity in a Light-Driven Na(+)-Pumping Rhodopsin. AB - Krokinobacter eikastus rhodopsin 2 (KR2) is a recently identified light-driven Na(+) pump from a marine bacterium. KR2 pumps Na(+) in NaCl solution but pumps H(+) in the absence of Na(+) and Li(+). The Na(+) transport mechanism in KR2 has been extensively studied, whereas understanding of the H(+) transport mechanism is very limited. Here we studied ion uptake mechanisms and H(+)-Na(+) selectivity using flash photolysis. The results show that decay of the blue-shifted M intermediate is dependent on both [Na(+)] and [H(+)], indicating that KR2 competitively uptakes Na(+) or H(+) upon M decay. Comprehensive concentration dependence of Na(+) and H(+) revealed that the rate constant of H(+) uptake (kH) was much larger than that of Na(+) uptake (kNa) with a ratio (kH/kNa) of >10(3). Therefore, KR2 pumps only H(+) when Na(+) and H(+) concentrations are similar. On the contrary, KR2 pumps Na(+) exclusively under physiological conditions in which [Na(+)] is much greater than [H(+)]. PMID- 26673198 TI - Nutrition in the Surgical Intensive Care Unit: The Cost of Starting Low and Ramping Up Rates. AB - BACKGROUND: Calorie/protein deficit in the surgical intensive care unit (SICU) is associated with worse clinical outcomes. It is customary to initiate enteral nutrition (EN) at a low rate and increase to goal (RAMP-UP). Increasing evidence suggests that RAMP-UP may contribute to iatrogenic malnutrition. We sought to determine what proportion of total SICU calorie/protein deficit is attributable to RAMP-UP. MATERIALS AND METHODS: This is a retrospective study of a prospectively collected registry of adult patients (N = 109) receiving at least 72 hours of EN in the SICU according to the RAMP-UP protocol (July 2012-June 2014). Subjects receiving only trophic feeds or with interrupted EN during RAMP UP were excluded. Deficits were defined as the amount of prescribed calories/protein minus the actual amount received. RAMP-UP deficit was defined as the deficit between EN initiation and arrival at goal rate. Data included demographics, nutritional prescription/delivery, and outcomes. RESULTS: EN was started at a median of 34.0 hours (interquartile range [IQR], 16.5-53.5) after ICU admission, with a mean duration of 8.7 +/- 4.3 days. The median total caloric deficit was 2185 kcal (249-4730), with 900 kcal (551-1562) attributable to RAMP UP (41%). The protein deficit was 98.5 g (27.5-250.4), with 51.9 g (20.6-83.3) caused by RAMP-UP (53%). CONCLUSIONS: In SICU patients initiating EN, the RAMP-UP period accounted for 41% and 53% of the overall caloric and protein deficits, respectively. Starting EN immediately at goal rate may eliminate a significant proportion of macronutrient deficit in the SICU. PMID- 26673199 TI - Nutrition Support in the Open Abdomen. AB - Early provision of enteral nutrition (EN) in critically ill and injured patients has become standard practice in surgical intensive care units (ICUs) due to its proven role in reducing septic complications. Increasingly, intensivists are confronted with patients with an open abdomen due to the use of damage control surgery and the recognition of the abdominal compartment syndrome; the role and timing of EN in these challenging patients continue to be debated. Patients with an open abdomen are often among the sickest in the ICU and hence could benefit from early nutrition support. However, the exposed abdominal viscera can understandably create anxiety regarding the initiation of EN; there is theoretic concern over exacerbation of bowel distention with resultant inability to close the abdomen and an increased aspiration risk due to paralytic ileus. Recent studies have investigated the utility of EN in the patient with an open abdomen, addressing these clinical concerns. The goal of this clinical review is to provide guidance to physicians caring for these complex patients. PMID- 26673200 TI - Effect of Probiotics on the Incidence of Healthcare-Associated Infections in Mechanically Ventilated Neurocritical Care Patients. AB - BACKGROUND: Healthcare-associated infections (HAIs) are seen in 17% of critically ill patients. Probiotics, live nonpathogenic microorganisms, may aid in reducing the incidence of infection in critically ill patients. We hypothesized that administration of probiotics would be safe and reduce the incidence of HAIs among mechanically ventilated neurocritical care patients. METHODS: We assembled 2 retrospective cohorts of mechanically ventilated neurocritical care patients. In the preintervention cohort from July 1, 2011, to December 31, 2011, probiotics were not used. In the postintervention group from July 1, 2012, to December 31, 2012, 1 g of a combination of Lactobacillus acidophilus and Lactobacillus helveticus was administered twice daily to all patients who were mechanically ventilated for more than 24 hours. RESULTS: There were a total of 167 patients included, 80 patients in the preintervention group and 87 patients in the postintervention group. No patients in the preintervention group received probiotics. Eighty-five (98%) patients in the postintervention group received probiotics for a median of 10 days (interquartile range, 4-20 days). There were 14 (18%) HAIs in the preintervention group and 8 (9%) HAIs in the postintervention group (P = .17). Ventilator days, lengths of stay, in-hospital mortality, and discharge disposition were similar between the pre- and postintervention groups. There were no cases of Lactobacillus bacteremia or other adverse events associated with probiotics use. CONCLUSION: Probiotics are safe to administer in neurocritical care patients; however, this study failed to demonstrate a significant decrease in HAIs or secondary outcomes associated with probiotics. PMID- 26673201 TI - Whole Egg Consumption Prevents Diminished Serum 25-Hydroxycholecalciferol Concentrations in Type 2 Diabetic Rats. AB - Type 2 diabetes (T2D) is characterized by vitamin D deficiency owing to increased urinary loss of 25-hydroxycholecalciferol (25D). Whole eggs are a rich source of vitamin D, particularly 25D, the circulating form that reflects status. Zucker diabetic (type 2) fatty (ZDF) rats and their lean counterparts were fed casein- or whole egg-based diets for 8 weeks. Whole egg consumption attenuated both hyperglycemia and hypertriglyceridemia, as well as reduced weight gain in ZDF rats compared to casein-fed diabetic rats. Circulating 25D was lower in casein fed ZDF rats compared to lean controls; however, ZDF rats fed whole egg exhibited the same circulating 25D concentration as casein-fed lean rats. These data suggest that dietary whole egg can attenuate metabolic anomalies, as well as maintain normal circulating 25D concentrations in T2D rats. This finding may support new dietary recommendations targeting vitamin D deficiency prevention in T2D. PMID- 26673202 TI - Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study. AB - BACKGROUND: Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE). METHODS: Twenty-five male patients (71 [64; 80] years) with wtATTR CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI) (n=14), and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months. RESULTS: A significant decrease of left ventricular (LV) myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03) by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006) was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75), LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; P=0.1), and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3) by echocardiography remained unchanged. CONCLUSION: This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction. PMID- 26673203 TI - Protein disorder reduced in Saccharomyces cerevisiae to survive heat shock. AB - Recent experiments established that a culture of Saccharomyces cerevisiae (baker's yeast) survives sudden high temperatures by specifically duplicating the entire chromosome III and two chromosomal fragments (from IV and XII). Heat shock proteins (HSPs) are not significantly over-abundant in the duplication. In contrast, we suggest a simple algorithm to " postdict " the experimental results: Find a small enough chromosome with minimal protein disorder and duplicate this region. This algorithm largely explains all observed duplications. In particular, all regions duplicated in the experiment reduced the overall content of protein disorder. The differential analysis of the functional makeup of the duplication remained inconclusive. Gene Ontology (GO) enrichment suggested over representation in processes related to reproduction and nutrient uptake. Analyzing the protein-protein interaction network (PPI) revealed that few network central proteins were duplicated. The predictive hypothesis hinges upon the concept of reducing proteins with long regions of disorder in order to become less sensitive to heat shock attack. PMID- 26673206 TI - The Association of American Veterinary Medical Colleges and Academic Veterinary Medicine-Creating the Profession of Veterinary Medicine for 50 Years. PMID- 26673204 TI - Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway. AB - Cholesterol efflux capacity associates strongly and negatively with the incidence and prevalence of human CVD. We investigated the relationships of HDL's size and protein cargo with its cholesterol efflux capacity using APOB-depleted serum and HDLs isolated from five inbred mouse strains with different susceptibilities to atherosclerosis. Like humans, mouse HDL carried >70 proteins linked to lipid metabolism, the acute-phase response, proteinase inhibition, and the immune system. HDL's content of specific proteins strongly correlated with its size and cholesterol efflux capacity, suggesting that its protein cargo regulates its function. Cholesterol efflux capacity with macrophages strongly and positively correlated with retinol binding protein 4 (RBP4) and PLTP, but not APOA1. In contrast, ABCA1-specific cholesterol efflux correlated strongly with HDL's content of APOA1, APOC3, and APOD, but not RBP4 and PLTP. Unexpectedly, APOE had a strong negative correlation with ABCA1-specific cholesterol efflux capacity. Moreover, the ABCA1-specific cholesterol efflux capacity of HDL isolated from APOE-deficient mice was significantly greater than that of HDL from wild-type mice. Our observations demonstrate that the HDL-associated APOE regulates HDL's ABCA1-specific cholesterol efflux capacity. These findings may be clinically relevant because HDL's APOE content associates with CVD risk and ABCA1 deficiency promotes unregulated cholesterol accumulation in human macrophages. PMID- 26673205 TI - Mapping the CgrA regulon of Rhodospirillum centenum reveals a hierarchal network controlling Gram-negative cyst development. AB - BACKGROUND: Several Gram-negative species undergo development leading to the formation of metabolically dormant desiccation resistant cysts. Recent analysis of cyst development has revealed that ~20 % of the Rhodospirillum centenum transcriptome undergo temporal changes in expression as cells transition from vegetative to cyst forms. It has also been established that one trigger for cyst formation is the synthesis of the signaling nucleotide 3', 5'- cyclic guanosine monophosphate (cGMP) that is sensed by a homolog of the catabolite repressor protein called CgrA. CgrA in the presence of cGMP initiate a cascade of gene expression leading to the development of cysts. RESULTS: In this study, we have used RNA-seq and chromatin immunoprecipitation (ChIP-Seq) techniques to define the CgrA-cGMP regulon. Our results indicate that disruption of CgrA leads to altered expression of 258 genes, 131 of which have been previously reported to be involved in cyst development. ChIP-seq analysis combined with transcriptome data also demonstrates that CgrA directly regulates the expression of numerous sigma factors and transcription factors several of which are known to be involved in cyst cell development. CONCLUSIONS: This analysis reveals the presence of CgrA binding sites upstream of many developmentally regulated genes including many transcription factors and signal transduction components. CgrA thus functions as master controller of the cyst development by initiating a hierarchal cascade of downstream transcription factors that induces temporal expression of encystment genes. PMID- 26673207 TI - Association of American Veterinary Medical Colleges (AAVMC): 50 Years of History and Service. AB - The mission of the Association of American Veterinary Medical Colleges (AAVMC) is to advance the quality of academic veterinary medicine. Founded in 1966 by the 18 US colleges of veterinary medicine and 3 Canadian colleges of veterinary medicine then in existence, the AAVMC is celebrating 50 years of public service. Initially, the AAVMC comprised the Council of Deans, the Council of Educators, and the Council of Chairs. In 1984, the tri-cameral structure was abandoned and a new governing structure with a board of directors was created. In 1997, the AAVMC was incorporated in Washington, DC and a common application service was created. Matters such as workforce issues and the cost of veterinary medical education have persisted for decades. The AAVMC is a champion of diversity in the veterinary profession and a strong advocate for One Health. The AAVMC has adopted a global perspective as more international colleges of veterinary medicine have earned COE accreditation and become members. PMID- 26673209 TI - The Changing Fiscal Environment for Academic Veterinary Medicine. AB - The fiscal environment for academic veterinary medicine has changed substantially over the past 50 years. Understanding the flux of state and federal government support and the implications for student debt, academic programs, and scholarly work is critical for planning for the future. The recent precipitous decline in public funding highlights the urgent need to develop and maintain an economically sustainable model that can adapt to the changing landscape and serve societal needs. PMID- 26673208 TI - Fifty Years of Evolving Partnerships in Veterinary Medical Education. AB - The Association of American Veterinary Medical College's (AAVMC's) role in the progression of academic veterinary medical education has been about building successful partnerships in the US and internationally. Membership in the association has evolved over the past 50 years, as have traditions of collaboration that strengthen veterinary medical education and the association. The AAVMC has become a source of information and a place for debate on educational trends, innovative pedagogy, and the value of a diverse learning environment. The AAVMC's relationship with the American Veterinary Medical Association Council on Education (AVMA COE), the accreditor of veterinary medical education recognized by the United Sates Department of Education (DOE), is highlighted here because of the key role that AAVMC members have played in the evolution of veterinary accreditation. The AAVMC has also been a partner in the expansion of veterinary medical education to include global health and One Health and in the engagement of international partners around shared educational opportunities and challenges. Recently, the association has reinforced its desire to be a truly international organization rather than an American organization with international members. To that end, strategic AAVMC initiatives aim to expand and connect the global community of veterinary educators to the benefit of students and the profession around the world. Tables in this article are intended to provide historical context, chronology, and an accessible way to view highlights. PMID- 26673210 TI - Animals Used in Research and Education, 1966-2016: Evolving Attitudes, Policies, and Relationships. AB - Since the inception of the Association of American Veterinary Medical Colleges (AAVMC), the use of animals in research and education has been a central element of the programs of member institutions. As veterinary education and research programs have evolved over the past 50 years, so too have societal views and regulatory policies. AAVMC member institutions have continually responded to these events by exchanging best practices in training their students in the framework of comparative medicine and the needs of society. Animals provide students and faculty with the tools to learn the fundamental knowledge and skills of veterinary medicine and scientific discovery. The study of animal models has contributed extensively to medicine, veterinary medicine, and basic sciences as these disciplines seek to understand life processes. Changing societal views over the past 50 years have provided active examination and continued refinement of the use of animals in veterinary medical education and research. The future use of animals to educate and train veterinarians will likely continue to evolve as technological advances are applied to experimental design and educational systems. Natural animal models of both human and animal health will undoubtedly continue to serve a significant role in the education of veterinarians and in the development of new treatments of animal and human disease. As it looks to the future, the AAVMC as an organization will need to continue to support and promote best practices in the humane care and appropriate use of animals in both education and research. PMID- 26673211 TI - Changing the Face of Veterinary Medicine: Research and Clinical Developments at AAVMC Institutions. AB - This paper provides a 50-year overview of research and clinical advances in AAVMC member colleges in four representative fields of veterinary medicine: oncology, vaccine development, production medicine, and public health. Though emphasis is on the progress since the mid-1960s, the salient background and associated personnel in each field are also identified to the extent that their description informs more recent events. Advances in board certification and post-graduate clinical and research educational opportunities are also described. PMID- 26673212 TI - Driving Success over the Past 50 Years-The Faculty in Academic Veterinary Medicine. AB - The faculty at member schools and colleges of the Association of American Veterinary Medical Colleges (AAVMC) are critical for continued progress in veterinary medicine. The success of those faculty members over the past 50 years has positioned veterinary medicine to engage an ever-widening array of opportunities, responsibilities, and societal needs. Yet the array of skills and accomplishments of faculty in academic veterinary medicine are not always visible to the public, or even within our profession. The quality and the wide range of their scholarship are reflected, in part, through the according of national and international awards and honors from organizations relevant to their particular areas of expertise. The goal of this study was to illustrate the breadth of expertise and the quality of the faculty at 34 schools/colleges of veterinary medicine by examining the diversity of organizations that have recognized excellence in faculty achievements through a variety of awards. PMID- 26673213 TI - Fifty Years in the Life of Veterinary Students. AB - Many changes in US veterinary colleges and their student bodies have occurred during the past 50 years. These have reflected US demographics in many ways. With these changes have come many changes in student life. The Association of American Veterinary Medical Colleges has played an important role in facilitating and tracking many of the changes by creating numerous opportunities for colleges to work together on issues related to admissions, diversity, and scholarly publication in the Journal of Veterinary Medical Education. PMID- 26673214 TI - Instruction and Curriculum in Veterinary Medical Education: A 50-Year Perspective. AB - Our knowledge of veterinary medicine has expanded greatly over the past 50 years. To keep pace with these changes and produce competent professionals ready to meet evolving societal needs, instruction within veterinary medical curricula has undergone a parallel evolution. The curriculum of 1966 has given way, shifting away from lecture-laboratory model with few visual aids to a program of active learning, significant increases in case- or problem-based activities, and applications of technology, including computers, that were unimaginable 50 years ago. Curricula in veterinary colleges no longer keep all students in lockstep or limit clinical experiences to the fourth year, and instead have moved towards core electives with clinical activities provided from year 1. Provided here are examples of change within veterinary medical education that, in the view of the authors, had positive impacts on the evolution of instruction and curriculum. These improvements in both how and what we teach are now being made at a more rapid pace than at any other time in history and are based on the work of many faculty and administrators over the past 50 years. PMID- 26673215 TI - History of the Journal of Veterinary Medical Education. AB - The Journal of Veterinary Medical Education (JVME), with the leadership of seven editors and two interim editors, grew from 33 pages of mostly news and commentary to become the premier source for information exchange in veterinary medical education. The first national publication of the Association of American Veterinary Medical Colleges (AAVMC) was a 21-page newsletter published in December 1973. This one-time newsletter was followed by volume 1, issue 1 of JVME, published in spring 1974 and edited by William W. Armistead. Richard Talbot was the second and longest serving editor, and under his leadership, JVME grew in the number and quality of papers. Lester Crawford and John Hubbell served as interim editors, maintaining quality and keeping JVME on track until a new editor was in place. Robert Wilson, Billy Hooper, Donal Walsh, Henry Baker, and the current editor, Daryl Buss, are major contributors to the success of JVME. The early history of the journal is described by Billy Hooper and followed by a brief history of the periods of each of the editors. This history concludes with objective and subjective evaluations of the impacts of JVME. PMID- 26673216 TI - A patient perspective on shared decision making in stage I non-small cell lung cancer: a mixed methods study. AB - BACKGROUND: Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with a stage I non-small cell lung cancer (NSCLC). Consequently, there is growing interest in studying the role of patients in treatment decision making. We studied how patients with stage I NSCLC perceived shared decision making (SDM) in general, and how they viewed different aspects of SDM. METHODS: A sequential mixed methods design was used, consisting of qualitative interviews (N=11), as well as a survey study (N=76) focusing on different SDM-related aspects. Participants were interviewed to understand their own experience with treatment decision making. In the survey study, patients rated the importance of 20 aspects of shared decision making that were identified during interviews. Descriptive analysis and explorative factor analysis were performed. RESULTS: We assessed six qualitative themes covering SDM aspects that were determined by patients to be important. The survey identified four SDM related factors with sufficient internal consistency, namely (1) 'guidance by clinician' (alpha=.741), (2) 'conduct of clinician' (alpha=.774); (3) 'preparation for treatment decision making' (alpha=.864); and (4) 'active role of patient in treatment decision making' (alpha=.782). Of these, clinician guidance was rated as most important by patients (M=3.61; SD=.44). Only 28.9% of patients in the survey study reported that both treatment options were discussed with them. CONCLUSIONS: Patients with a stage I NSCLC found clinician guidance to be important when making treatment decisions. Nevertheless, the majority of patients reported not being offered both treatment options, which might have influenced this finding. PMID- 26673218 TI - Predicting Agenesis of the Mandibular Second Premolar from Adjacent Teeth. AB - Early diagnosis of agenesis of the mandibular second premolar (P2) enhances management of the dental arch in the growing child. The aim of this study was to explore the relationship in the development of the mandibular first molar (M1) and first premolar (P1) at early stages of P2 (second premolar). Specifically, we ask if the likelihood of P2 agenesis can be predicted from adjacent developing teeth. We selected archived dental panoramic radiographs with P2 at crown formation stages (N = 212) and calculated the likelihood of P2 at initial mineralisation stage 'Ci' given the tooth stage of adjacent teeth. Our results show that the probability of observing mandibular P2 at initial mineralisation stage 'Ci' decreased as both the adjacent P1 and M1 matured. The modal stage at P2 'Ci' was P1 'Coc' (cusp outline complete) and M1 'Crc' (crown complete). Initial mineralisation of P2 was observed up to P1 'Crc' and M1 stage 'R1/2' (root half). The chance of observing P2 at least 'Coc' (coalescence of cusps) was considerably greater prior to these threshold stages compared to later stages of P1 and M1. These findings suggest that P2 is highly unlikely to develop if P1 is beyond 'Crc' and M1 is beyond 'R1/2'. PMID- 26673217 TI - Long-Lived alphaMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection. AB - alphaMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. alphaMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of alphaMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, alphaMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while alphaMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in alphaMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in alphaMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the alphaMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the alphaMUPA myocardium. alphaMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of alphaMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life long increased ischemic tolerance in alphaMUPA mice, indicating the attenuation of cardiac aging. alphaMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR. PMID- 26673220 TI - Factor Structure of Subjective Well-Being in Iran. AB - Subjective well-being is predominantly conceived as having 3 components: life satisfaction, positive affect, and negative affect. This article reports 2 studies that seek to investigate the factor structure of subjective well-being in Iran. One-, two-, and three-factor models of subjective well-being were evaluated using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). The results of Study 1 (N = 2,197) and Study 2 (N = 207) show that whereas the 1- and 2-factor models do not fit the data well, the 3-factor model provides an adequate fit. These results indicate that the 3 components of subjective well-being constitute 3 interrelated, yet distinct, factors. The analyses demonstrate how traditional CFA and ESEM can be combined to obtain a clear picture of the measurement model of subjective well-being and generate new insights about individual items and cross-loadings needed to derive more parsimonious measures. Nuances relating to the assessment of subjective well being in more collectivist and Muslim countries are discussed. PMID- 26673221 TI - Correction: Tolerance of Organ Transplant Recipients to Physical Activity during a High-Altitude Expedition: Climbing Mount Kilimanjaro. PMID- 26673219 TI - Gender Difference in Associations between Chronic Temporomandibular Disorders and General Quality of Life in Koreans: A Cross-Sectional Study. AB - BACKGROUND: Chronic temporomandibular disorder (TMD) is known to have strong correlations with psychological factors and to display gender disparity. However, while chronic TMD is known to affect quality of life, large-scale studies investigating the influence on quality of life by gender are scarce. METHODS: This cross-sectional study assessed the data of 17,198 participants aged >=19 years who completed chronic TMD and EuroQol-5 Dimension sections in the 4th Korean National Health and Nutrition Examination Survey (2007-2009). We adjusted for covariates (health behavior, sociodemographic factors) in regression analysis for complex sampling design to calculate regression coefficients and 95% CIs for gender difference in the association between chronic TMD and quality of life. We also evaluated which covariates of somatic health, mental health, health behavior, and sociodemographic factors weakened the relationship between TMD and EQ-5D. RESULTS: Prevalence of chronic TMD was 1.6% (men 1.3%, women 1.8%), and chronic TMD persisted to negatively impact quality of life even after adjusting for confounding variables. Low sociodemographic factors and health behavior had a negative effect on quality of life. Somatic health and mental health were most affected by chronic TMD. As for quality of life, women were affected to a greater extent than men by TMD. Women were more affected by osteoarthritis and general mental health (stress, depressive symptoms, and thoughts of suicide), and men by employment. CONCLUSIONS: These results imply that chronic diseases and psychological factors are important in chronic TMD, and that there may be physiological and pathological gender differences in TMD. PMID- 26673222 TI - Motor Cost Influences Perceptual Decisions. AB - Perceptual decision making has been widely studied using tasks in which subjects are asked to discriminate a visual stimulus and instructed to report their decision with a movement. In these studies, performance is measured by assessing the accuracy of the participants' choices as a function of the ambiguity of the visual stimulus. Typically, the reporting movement is considered as a mere means of reporting the decision with no influence on the decision-making process. However, recent studies have shown that even subtle differences of biomechanical costs between movements may influence how we select between them. Here we investigated whether this purely motor cost could also influence decisions in a perceptual discrimination task in detriment of accuracy. In other words, are perceptual decisions only dependent on the visual stimulus and entirely orthogonal to motor costs? Here we show the results of a psychophysical experiment in which human subjects were presented with a random dot motion discrimination task and asked to report the perceived motion direction using movements of different biomechanical cost. We found that the pattern of decisions exhibited a significant bias towards the movement of lower cost, even when this bias reduced performance accuracy. This strongly suggests that motor costs influence decision making in visual discrimination tasks for which its contribution is neither instructed nor beneficial. PMID- 26673223 TI - The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part I: Ultrasound anatomy and examination technique and W. Krzyzanowski, M. Tarczynska The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part II: Examples of labral pathologies. PMID- 26673224 TI - TM6SF2 may drive postprandial lipoprotein cholesterol toxicity away from the vessel walls to the liver in NAFLD. PMID- 26673226 TI - HPV vaccination: acceptance and influencing factors among young men in Germany. AB - AIMS: This study aims to determine the factors that influence the acceptance of the HPV vaccination among German males. PATIENT & METHODS: In 2014, we conducted a population-based cross-sectional study in men aged 15-25 years. A questionnaire was mailed to male trainees of the Bayerische Motorenwerke AG (BMW) insured at the BMW health insurance company. RESULTS: The response rate was 10.8%. Of the 378 included men, 74.1% would agree to receive HPV vaccination. Most men primarily consult their physician for health-related topics, but 92.9% had never been informed about HPV infection, risk factors and prevention methods by their doctor. CONCLUSION: Our results demonstrate a high acceptance of male HPV vaccination. Education about HPV infection is low and should be intensified by medical professionals. PMID- 26673225 TI - Open and Calm--a randomized controlled trial evaluating a public stress reduction program in Denmark. AB - BACKGROUND: Prolonged psychological stress is a risk factor for illness and constitutes an increasing public health challenge creating a need to develop public interventions specifically targeting stress and promoting mental health. The present randomized controlled trial evaluated health effects of a novel program: Relaxation-Response-based Mental Health Promotion (RR-MHP). METHODS: The multimodal, meditation-based course was publicly entitled "Open and Calm" (OC) because it consistently trained relaxed and receptive ("Open") attention, and consciously non-intervening ("Calm") witnessing, in two standardized formats (individual or group) over nine weeks. Seventy-two participants who complained to their general practitioner about reduced daily functioning due to prolonged stress or who responded to an online health survey on stress were randomly assigned to OC formats or treatment as usual, involving e.g., unstandardized consultations with their general practitioner. Outcomes included perceived stress, depressive symptoms, quality of life, sleep disturbances, mental health, salivary cortisol, and visual perception. Control variables comprised a genetic stress-resiliency factor (serotonergic transporter genotype; 5-HTTLPR), demographics, personality, self-reported inattentiveness, and course format. RESULTS: Intent-to-treat analyses showed significantly larger improvements in OC than in controls on all outcomes. Treatment effects on self-reported outcomes were sustained after 3 months and were not related to age, gender, education, or course format. The dropout rate was only 6 %. CONCLUSIONS: The standardized OC program reduced stress and improved mental health for a period of 3 months. Further testing of the OC program for public mental health promotion and reduction of stress-related illnesses is therefore warranted. A larger implementation is in progress. TRIAL REGISTRATION: ClinicalTrials.gov.: NCT02140307. Registered May 14 2014. PMID- 26673227 TI - Xanthine oxidoreductase activity assay in tissues using stable isotope-labeled substrate and liquid chromatography high-resolution mass spectrometry. AB - Studies of pathological mechanisms and XOR inhibitor characterization, such as allopurinol, febuxostat, and topiroxostat, require accurate and sensitive measurements of XOR activity. However, the established assays have some disadvantages such as susceptibility to endogenous substances such as uric acid (UA), xanthine, or hypoxanthine. Here, we aimed to develop a novel XOR activity assay utilizing a combination of high-performance liquid chromatography (LC) and high-resolution mass spectrometry (HRMS) for tissues such as the liver, kidney, and plasma. Stable isotope-labeled [(15)N2]-xanthine was utilized as substrate and the production of [(15)N2]-uric acid was determined. [(15)N2]-UA production by XOR was dependent on the amounts of [(15)N2]-xanthine and enzyme and the time of reaction. Because high concentrations of endogenous xanthine and hypoxanthine affect XOR activities, we employed a multi-component analysis using LC/HRMS to improve the accuracy of XOR activity assay. Quantification of [(15)N2]-UA was validated and showed good linearity, accuracy, and precision. We measured the XOR activities of retired ICR mice using [(15)N2]-xanthine and LC/MS. The XOR activities in plasma, kidney, and liver samples were 38.1+/-0.7, 158+/-5, 928+/ 25pmol/min/mg of protein, respectively (mean+/-SD, n=5). Furthermore, we measured the XOR activities in the same samples using the LC/ultraviolet and LC/fluorescence (FL) methods. The level of [(15)N2]-xanthine oxidation by XOR was equal to that of xanthine oxidation and approximately 7.9-8.9 times higher than that of pterin oxidation. We found a good correlation between XOR activities examined using LC/MS assay with [(15)N2]-xanthine and those examined using LC/FL assay with pterin. This result suggested that although both the LC/MS assay with [(15)N2]-xanthine and the LC/FL assay with pterin were useful, the former provided information regarding XOR activities that more directly reflected the physiological condition than the latter. PMID- 26673228 TI - High-performance thin-layer chromatography as a fast screening tool for phosphorylated peptides. AB - This study aimed at developing a rapid chromatographic assay to monitor phosphorylation sites in peptides. For the analysis of nociceptive signal transduction pathways, the detection of phosphorylated proteins/peptides plays a fundamental role. To get further insights in the phosphorylation mechanism of protein kinase C-epsilon (PKC-epsilon) and protein kinase A (PKA), potential targets were divided into subsections resulting in peptides that contain only one possible phospho-binding site. The use of high-performance thin-layer chromatography (HPTLC) offers the possibility of a high throughput of samples and the advantage of a quick sample clean-up. A combined strategy of an effect directed overlay procedure on the TLC plate using specific antibodies (immunostaining, HPTLC-IS) as well as a parallel, direct mass spectrometric methodology by HPTLC-MALDI-TOF-MS was developed. With regard to HPTLC-IS, validation of the data exhibited a lower limit of detection than the traditionally used protein derivatization reagent fluorescamine. Besides the identification of the phosphorylated peptides, a semi-quantitative estimation can be performed with HPTLC-IS. PMID- 26673229 TI - Simultaneous determination of phosphatidylcholine-derived quaternary ammonium compounds by a LC-MS/MS method in human blood plasma, serum and urine samples. AB - The determination of circulating trimethylamine-N-oxide (TMAO), choline, betaine, l-carnitine and O-acetyl-l-carnitine concentration in different human matrices is of great clinical interest. Recent results highlighted the prognostic value of TMAO and quaternary ammonium containing metabolites in the field of cardiovascular and kidney diseases. Herein, we report a method for the rapid and simultaneous measurement of closely related phosphatidylcholine-derived metabolites in three different biological matrices by stable isotope dilution assay. Plasma, serum and urine samples were simply deproteinized and separated by HILIC-chromatography. Detection and quantification were performed using LC-MS/MS with electrospray ionization in positive mode. For accuracy and precision, full calibration was performed covering more than the full reference range. Assay performance metrics include intra- and interday imprecision were below 10% for all analytes. To exclude matrix effects standard addition methods were applied for all matrices. It was shown that calibration standards and quality control prepared in water can be used instead of matrix-matched calibration and controls. The LC/MS/MS-based assay described in this article may improve future clinical studies evaluating TMAO and related substances as prognostic markers for cardiovascular risk and all-cause mortality in different patient populations. PMID- 26673230 TI - Highly sensitive and selective detection of human carboxylesterase 1 activity by liquid chromatography with fluorescence detection. AB - Human carboxylesterases 1 (hCE1), one of the most important human drug metabolizing enzymes, catalyzes the hydrolysis of a large number of structurally diverse of endogenous and exogenous substrates. However, a practical, reliable and sensitive method for the precise measurement of hCE1 activities in complex biological samples has been rarely reported. In this study, a liquid chromatography-fluorescence detection (LC-FD) based method was developed for highly selective and sensitive measurement of hCE1 activities in human tissue and cell preparations. This method was based on the fluorimetric detection of HMBT, the hydrolyzed product of BMBT which was a newly developed specific probe substrate for hCE1. The developed LC-FD method was fully validated in terms of specificity, sensitivity, linearity, precision, recovery and stability. With the help of LC separation, most polar endogenous compounds in biological samples could be eluted in the column dead time, which is very beneficial for accurate determination of hCE1 activities in complex biological samples. The lower limit of quantification for HMBT (product of hCE1) of this LC-FD based method was as low as 20nM, which was quite lower than other reported methods. The method also exhibited good precision, both intra- and inter- assay variances were both lower than 2.5%. Furthermore, the newly developed method was successfully applied to measure hCE1 activity in human liver preparations from individual donors (n=12), as well as in homogenates from eleven different human cell lines. All these findings combined with this practical method are very helpful for the deep understanding of the expression and function of hCE1 in human biological samples. PMID- 26673232 TI - Thymic Small Cell Neuroendocrine Carcinoma Displayed on 18F-FDG PET/CT Imaging. AB - A 52-year-old man presented with chest distress and low back pain for 1 month. CT examination displayed a thymic tumor with the metastases to bilateral lungs as well as mediastinal and bilateral hilar lymph nodes. To evaluate the involved extent of the disease, F-FDG PET/CT scan was carried out, which showed that in addition to the thymic mass, multiple foci of abnormally increased FDG activity in the bilateral lungs, neck and chest lymph nodes, and bones were observed. Finally, the biopsy of the mass confirmed the diagnosis of thymic small cell neuroendocrine carcinoma. PMID- 26673233 TI - Metastatic Malignant Fibrous Histiocytoma Infiltrating Sigmoid Colon: A Case Diagnosed With the Help of 18F-FDG PET/CT. AB - Metastatic malignant fibrous histiocytoma (MFH) in the colon is extremely rare, although MFH is one of the most common soft tissue sarcomas in adults. We report the case of a 45-year-old woman with metastatic MFH in the sigmoid colon, descending colon, and right lung with FDG PET/CT findings. PMID- 26673231 TI - Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia. AB - Streptococcus (S.) pneumoniae is the most common causative pathogen in community acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/-) and wild type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Deltacps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Deltacps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2. PMID- 26673234 TI - A Case of Asymptomatic Venous Air Embolism Demonstrated on 18F FDG PET/CT. AB - We present the findings on F FDG PET/CT in connection with iatrogenic venous air embolism. The patient was referred for a posttreatment evaluation PET/CT for peripheral T-cell lymphoma. On the PET images, an intense FDG-uptake was seen in the injected vein. Simultaneous non-contrast-enhanced CT showed air bubbles of various sizes within the affected veins. Because no intravenous contrast was administered, we conclude that the source of venous air embolism was either the insertion of the peripheral intravenous cannula and/or the injection of F FDG, via a power injector, 1 hour before the scan. PMID- 26673235 TI - Prostate Lymphoma Complicated With Prostatorectal Fistula and Multifocal Infection After Chemotherapy. AB - A 67-year-old man with a biopsy proving prostate diffuse large B-cell lymphoma was referred for an F-FDG PET/CT scan for postchemotherapy treatment monitoring. The FDG PET/CT scan revealed a significant reduction of prostate lymphoma and a prostatorectal fistula formation. The patient developed Klebsiella pneumoniae sepsis, and a follow-up FDG PET/CT 3 months later revealed multifocal lung, bone, and muscle infection. The FDG PET/CT scans of this patient not only demonstrated the effectiveness of chemotherapy for prostate lymphoma but also the complications of a prostatorectal fistula and multiple infectious foci. PMID- 26673236 TI - Black Hole in the Breast. AB - We report an unusual artifact, which was seen on a routine preoperative chest radiograph performed in a patient with breast cancer, before an elective mastectomy. Subsequently, this was identified to be secondary to a preoperative sentinel node injection. The report discusses the diagnostic dilemma caused by this artifact and raises the awareness of this possibility in patients undergoing these commonly performed procedures and investigations. PMID- 26673237 TI - Three-Phase 99mTc MDP Bone Scintigraphy and SPECT-CT in Sinus Tarsi Syndrome. AB - Sinus tarsi syndrome is a pain in the lateral side of the hind foot that is responsive to injection of local anesthetic agents. We report a case of a 42-year old man who presented with pain over the lateral aspect of the right foot. Laboratory investigations and x-ray were normal. Bone scintigraphy showed hyperemia and increase tracer uptake in right hind foot. SPECT-CT localizes this uptake at the inferior aspect of the talus and superior aspects of the calcaneus. Diagnosis of sinus tarsi syndrome was made on the basis of history, clinical examination, and bone scintigraphy findings. Local conservative therapy was initiated. PMID- 26673238 TI - 18F-FDG PET/CT in a Patient With Glomus Vagale Paraganglioma and Eisenmenger Syndrome: Searching for the Missing Link? AB - There is emerging evidence linking cyanotic heart disease and pheochromocytoma paraganglioma through a proposed hypoxia pathway. We present a 59-year-old woman with known Eisenmenger syndrome secondary to delayed diagnosis of ventricular septal defect, in whom F-FDG PET/CT provided comprehensive evaluation of both an F-FDG-avid left glomus vagale paraganglioma and also increased right ventricular myocardial glucose metabolism in response to severe pulmonary hypertension in the chronic shunting state. PMID- 26673239 TI - Dumbbell-Shaped Activity on Meckel's Scintigraphy Caused by Hiatal Hernia. AB - A 13-month-old underwent Meckel's scintigraphy to evaluate a cause of melena. The images revealed a dumbbell-shaped activity. One side of dumbbell was located in the midline lower chest, whereas another side with similar intensity was in the normal location of the stomach. A subsequent contrast CT demonstrated a large hiatal hernia. PMID- 26673240 TI - Spectrum of 68Ga-DOTA TATE Uptake in Patients With Neuroendocrine Tumors. AB - PURPOSE: To analyze the biodistribution of Ga-DOTA-TATE in the normal tissues and uptake in benign, indeterminate, and malignant lesions in a population of patients with known neuroendocrine tumors (NET) using semiquantitative standardized uptake values (SUV) measurements. METHODS: One hundred four consecutively scanned patients (51 men and 53 women; mean age, 56.4 years) with confirmed diagnosis of NET underwent PET/CT 1 hour after administration of Ga DOTA-TATE. SUVmean, and SUVmax were measured in 37 normal anatomical structures for each patient. Abnormal uptake was divided into benign, indeterminate, and malignant categories based on imaging characteristic, clinical follow-up, and pathology. RESULTS: High physiologic uptake (SUVmax > 7) was observed in spleen, renal parenchyma, adrenal glands, pituitary gland, stomach, and liver (in decreasing order). Moderate uptake (3.5-7) was present in the prostate, jejunum, pancreas, ileum, and salivary glands. Mild uptake (2-3.5) was present in the uterus, colon, thyroid, rectum, and skeleton. A total of 678 lesions (limited to 5 lesions with highest uptake per organ) were included in the analysis, including 127 benign and 54 indeterminate lesions. Uptake was significantly higher in malignant lesions than in benign lesions, but an overlap was noted between the groups. CONCLUSIONS: Ga-DOTA TATE uptake in normal and abnormal structures is highly variable in patients with NET. SUV is a useful measure for characterizing benign versus malignant lesions. Anatomical and clinical correlation may be necessary to characterize foci of intermediate uptake. PMID- 26673241 TI - Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra arterially for Liver Metastases. AB - AIM: In patients with progressive, metastatic neuroendocrine tumors (NET), intra arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA] octreotide, 22 +/- 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 +/- 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. METHODS: Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. RESULTS: ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA] octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than In-[DTPA] octreotide but without any significant difference in other organs (spleen, kidneys, and liver). CONCLUSIONS: Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate. PMID- 26673242 TI - Quality and Safety in Health Care, Part VIII: Introduction to Medication Safety. AB - Injuries from medication are common and often preventable. Fortunately, there are many steps that can be taken to increase medication safety. Adopting a culture of safety including more reporting of medication errors and thorough investigation of their causes, better training including medical and communication skills, adopting superior procedures, and enhanced utilization of technology are all very helpful in reducing adverse events from drugs. The nursing staff is an important line of protection against patient injury from drug errors. The final line of protection is the patient and the patient's family, so educating them about their medical condition, their medication regimen, and how to participate in the process of staying healthy is essential for medication safety. PMID- 26673243 TI - Metabolic Activity by 18F-FDG-PET/CT Is Prognostic for Stage I and II Pancreatic Cancer. AB - PURPOSE: Metabolic activity, as defined by F-FDG uptake on PET, is a prognostic marker for multiple malignancies; however, no study has examined the prognostic value of imaging with FDG PET in stage I and II pancreatic cancer. We examined the value of PET FDG uptake in early-stage pancreatic cancer patients. METHODS: We identified patients with early-stage pancreatic cancer (I-II) who had FDG PET scan performed as part of their preoperative evaluation. The patients were divided into either high or low FDG uptake according to the median primary tumor standard uptake value (SUVmax). Our primary end points were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier estimate was used for survival analysis. Pathologic data were compared using the Fisher exact and chi tests. RESULTS: One hundred five patients were identified: 51 patients with low FDG uptake and 54 patients with high FDG uptake. Eighty-five patients (81%) had PET avid tumors, whereas 20 (19%) patients did not. High FDG uptake correlated with pathologic stage (P = 0.012). Patients with low FDG uptake had significantly better median OS than patients with high FDG uptake (28 vs. 16 months; P = 0.036). Patients with low-FDG uptake had significantly longer median RFS than patients with high FDG uptake (14 vs. 12 months; P = 0.049). CONCLUSIONS: Low FDG uptake in PET scans in patients with stage I and II pancreatic cancer correlates with improved OS and RFS. This supports the concept that glucose metabolic pathways are important in pancreatic cancer biology and that PET scan activity can be used as a prognostic biomarker after pancreatectomy. PMID- 26673245 TI - Association of calprotectin with leukocyte chemotactic and inflammatory mediators following acute aerobic exercise. AB - The objective of this study was to examine whether acute aerobic exercise mediated calprotectin in plasma would be associated with monocyte chemotactic protein-1 (MCP-1), myeloperoxidase (MPO), and interleukin-6 (IL-6) in healthy individuals. Eleven healthy participants, aged 18 to 30 years, were recruited to perform a 30-min bout of aerobic exercise at 75% maximal oxygen uptake. Acute aerobic exercise elicited a significant elevation across time in plasma calprotectin, MCP-1, MPO, and IL-6. Body mass index (BMI) was positively correlated with calprotectin area-under-the-curve with "respect to increase" (AUCi) and IL-6 AUCi. Furthermore, calprotectin AUCi was positively correlated with IL-6 AUCi and MPO AUCi, even after controlling for BMI. Although MPO AUCi was positively correlated with IL-6 AUCi, this relationship no longer existed after controlling for BMI. These results suggest that acute aerobic exercise could mediate innate immune response associated with calprotectin and its related leukocyte chemotactic and inflammatory mediators, especially in individuals with elevated BMI. PMID- 26673244 TI - A novel human leiomyoma tissue derived matrix for cell culture studies. AB - BACKGROUND: The composition of the matrix molecules is important in in vitro cell culture experiments of e.g. human cancer invasion and vessel formation. Currently, the mouse Engelbreth-Holm-Swarm (EHS) sarcoma-derived products, such as Matrigel(r), are the most commonly used tumor microenvironment (TME) mimicking matrices for experimental studies. However, since Matrigel(r) is non-human in origin, its molecular composition does not accurately simulate human TME. We have previously described a solid 3D organotypic myoma disc invasion assay, which is derived from human uterus benign leiomyoma tumor. Here, we describe the preparation and analyses of a processed, gelatinous leiomyoma matrix, named Myogel. METHODS: A total protein extract, Myogel, was formulated from myoma. The protein contents of Myogel were characterized and its composition and properties compared with a commercial mouse Matrigel(r). Myogel was tested and compared to Matrigel(r) in human cell adhesion, migration, invasion, colony formation, spheroid culture and vessel formation experiments, as well as in a 3D hanging drop video image analysis. RESULTS: We demonstrated that only 34% of Myogel's molecular content was similar to Matrigel(r). All test results showed that Myogel was comparable with Matrigel(r), and when mixed with low-melting agarose (Myogel LMA) it was superior to Matrigel(r) in in vitro Transwell(r) invasion and capillary formation assays. CONCLUSIONS: In conclusion, we have developed a novel Myogel TME matrix, which is recommended for in vitro human cell culture experiments since it closely mimics the human tumor microenvironment of solid cancers. PMID- 26673246 TI - Acute consumption of p-synephrine does not enhance performance in sprint athletes. AB - P-Synephrine is a protoalkaloid widely used as an ergogenic aid in sports. This substance has been included in the World Anti-Doping Agency monitoring program, although scientific information about its effects on performance and athletes' well-being is scarce. The purpose of this investigation was to determine the effectiveness of p-synephrine to increase performance in sprint athletes. In a randomized and counterbalanced order, 13 experienced sprinters performed 2 acute experimental trials after the ingestion of p-synephrine (3 mg.kg(-1)) or after the ingestion of a placebo (control trial). Forty-five minutes after the ingestion of the substances, the sprinters performed a squat jump, a countermovement jump, a 15-s repeated jump test, and subsequently performed 60-m and 100-m simulated sprint competitions. Self-reported questionnaires were used to assess side-effect prevalence. In comparison with the control trial, the ingestion of p-synephrine did not change countermovement jump height (37.4 +/- 4.2 vs 36.7 +/- 3.3 cm, respectively; P = 0.52), squat jump height (34.4 +/- 3.6 vs 33.9 +/- 3.7 cm; P = 0.34), or average 15-s repeated jumps height (31.8 +/- 4.1 vs 32.2 +/- 3.6 cm; P = 0.18). P-Synephrine did not modify maximal running speed during the 60-m (9.0 +/- 0.5 vs 9.0 +/- 0.4 m.s(-1), respectively; P = 0.55) and 100-m sprint competitions (8.8 +/- 0.5 vs 8.8 +/- 0.5 m.s(-1), respectively; P = 0.92). The ingestion of p-synephrine did not alter the prevalence of headache, gastrointestinal discomforts, muscle pain, or insomnia during the hours following the tests. Acute consumption of 3 mg.kg(-1) of p synephrine was ineffective to increase performance in competitive sprint athletes. Moreover, p-synephrine did not increase the occurrence of side effects after the competition. PMID- 26673248 TI - Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. AB - Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL 37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50% killing of F. tularensis at a concentration of 12.5 MUM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections. PMID- 26673250 TI - Biometric Denture Space- Concept of Neutral Zone Revisited Using A Hydrocolloid Impression Material. AB - Though the concept of neutral zone in making complete denture and its significance are well known, the material of choice has always been experimented to achieve better results. Recording of neutral zone using irreversible hydrocolloid (Alginate) as a material of choice would make the way of recording the neutral zone easier, as well as comfortable for the patient, when compared with other materials used for the purpose. This article describes the method of recording the biometric denture space (neutral zone) using hydrocolloid impression material which is most commonly used in everyday dental practice. PMID- 26673251 TI - Editorial. PMID- 26673249 TI - Long-term lamivudine for chronic hepatitis B and cirrhosis: A real-life cohort study. AB - AIM: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM). METHODS: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups. RESULTS: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group. CONCLUSION: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths. PMID- 26673253 TI - Through the eyes of a chemist. PMID- 26673252 TI - CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts. AB - The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research. PMID- 26673254 TI - Polymer synthesis: To react the impossible ring. PMID- 26673255 TI - Glycofullerenes: Sweet fullerenes vanquish viruses. PMID- 26673256 TI - Supramolecular pathways: Accessible self-assembly. PMID- 26673257 TI - Rhodium roles. PMID- 26673258 TI - Supramolecular catalysis: A rotaxane with the golden touch. PMID- 26673259 TI - Controlling and imaging biomimetic self-assembly. AB - The self-assembly of chemical entities represents a very attractive way to create a large variety of ordered functional structures and complex matter. Although much effort has been devoted to the preparation of supramolecular nanostructures based on different chemical building blocks, an understanding of the mechanisms at play and the ability to monitor assembly processes and, in turn, control them are often elusive, which precludes a deep and comprehensive control of the final structures. Here the complex supramolecular landscape of a platinum(II) compound is characterized fully and controlled successfully through a combination of supramolecular and photochemical approaches. The supramolecular assemblies comprise two kinetic assemblies and their thermodynamic counterpart. The monitoring of the different emission properties of the aggregates, used as a fingerprint for each species, allows the real-time visualization of the evolving self-assemblies. The control of multiple supramolecular pathways will help the design of complex systems in and out of their thermodynamic equilibrium. PMID- 26673260 TI - Real-time observation of multiexcitonic states in ultrafast singlet fission using coherent 2D electronic spectroscopy. AB - Singlet fission is the spin-allowed conversion of a spin-singlet exciton into a pair of spin-triplet excitons residing on neighbouring molecules. To rationalize this phenomenon, a multiexcitonic spin-zero triplet-pair state has been hypothesized as an intermediate in singlet fission. However, the nature of the intermediate states and the underlying mechanism of ultrafast fission have not been elucidated experimentally. Here, we study a series of pentacene derivatives using ultrafast two-dimensional electronic spectroscopy and unravel the origin of the states involved in fission. Our data reveal the crucial role of vibrational degrees of freedom coupled to electronic excitations that facilitate the mixing of multiexcitonic states with singlet excitons. The resulting manifold of vibronic states drives sub-100 fs fission with unity efficiency. Our results provide a framework for understanding singlet fission and show how the formation of vibronic manifolds with a high density of states facilitates fast and efficient electronic processes in molecular systems. PMID- 26673261 TI - Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia. AB - Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis. PMID- 26673263 TI - Completely recyclable biopolymers with linear and cyclic topologies via ring opening polymerization of gamma-butyrolactone. AB - Ring-opening polymerization (ROP) is a powerful synthetic methodology for the chemical synthesis of technologically important biodegradable aliphatic polyesters from cyclic esters or lactones. However, the bioderived five-membered gamma-butyrolactone (gamma-BL) is commonly referred as 'non-polymerizable' because of its low strain energy. The chemical synthesis of poly(gamma butyrolactone) (PgammaBL) through the ROP process has been realized only under ultrahigh pressure (20,000 atm, 160 degrees C) and only produces oligomers. Here we report that the ROP of gamma-BL can, with a suitable catalyst, proceed smoothly to high conversions (90%) under ambient pressure to produce PgammaBL materials with a number-average molecular weight up to 30 kg mol(-1) and with controlled linear and/or cyclic topologies. Remarkably, both linear and cyclic PgammaBLs can be recycled back into the monomer in quantitative yield by simply heating the bulk materials at 220 degrees C (linear polymer) or 300 degrees C (cyclic polymer) for one hour, which thereby demonstrates the complete recyclability of PgammaBL. PMID- 26673264 TI - Synthesis of 'unfeasible' zeolites. AB - Zeolites are porous aluminosilicate materials that have found applications in many different technologies. However, although simulations suggest that there are millions of possible zeolite topologies, only a little over 200 zeolite frameworks of all compositions are currently known, of which about 50 are pure silica materials. This is known as the zeolite conundrum--why have so few of all the possible structures been made? Several criteria have been formulated to explain why most zeolites are unfeasible synthesis targets. Here we demonstrate the synthesis of two such 'unfeasible' zeolites, IPC-9 and IPC-10, through the assembly-disassembly-organization-reassembly mechanism. These new high-silica zeolites have rare characteristics, such as windows that comprise odd-membered rings. Their synthesis opens up the possibility of preparing other zeolites that have not been accessible by traditional solvothermal synthetic methods. We envisage that these findings may lead to a step change in the number and types of zeolites available for future applications. PMID- 26673262 TI - Highly branched and loop-rich gels via formation of metal-organic cages linked by polymers. AB - Gels formed via metal-ligand coordination typically have very low branch functionality, f, as they consist of ~2-3 polymer chains linked to single metal ions that serve as junctions. Thus, these materials are very soft and unable to withstand network defects such as dangling ends and loops. We report here a new class of gels assembled from polymeric ligands and metal-organic cages (MOCs) as junctions. The resulting 'polyMOC' gels are precisely tunable and may feature increased branch functionality. We show two examples of such polyMOCs: a gel with a low f based on a M2L4 paddlewheel cluster junction and a compositionally isomeric one of higher f based on a M12L24 cage. The latter features large shear moduli, but also a very large number of elastically inactive loop defects that we subsequently exchanged for functional ligands, with no impact on the gel's shear modulus. Such a ligand substitution is not possible in gels of low f, including the M2L4-based polyMOC. PMID- 26673265 TI - Catalytic formal [2+2+1] synthesis of pyrroles from alkynes and diazenes via Ti(II)/Ti(IV) redox catalysis. AB - Pyrroles are structurally important heterocycles. However, the synthesis of polysubstituted pyrroles is often challenging. Here, we report a multicomponent, Ti-catalysed formal [2+2+1] reaction of alkynes and diazenes for the oxidative synthesis of penta- and trisubstituted pyrroles: a nitrenoid analogue to classical Pauson-Khand-type syntheses of cyclopentenones. Given the scarcity of early transition-metal redox catalysis, preliminary mechanistic studies are presented. Initial stoichiometric and kinetic studies indicate that the mechanism of this reaction proceeds through a formally Ti(II)/Ti(IV) redox catalytic cycle, in which an azatitanacyclobutene intermediate, resulting from [2+2] alkyne + Ti imido coupling, undergoes a second alkyne insertion followed by reductive elimination to yield pyrrole and a Ti(II) species. The key component for catalytic turnover is the reoxidation of the Ti(II) species to a Ti(IV) imido via the disproportionation of an eta(2)-diazene-Ti(II) complex. PMID- 26673267 TI - Nickel-catalysed Suzuki-Miyaura coupling of amides. AB - The Suzuki-Miyaura coupling has become one of the most important and prevalent methods for the construction of C-C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon-heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki-Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C-N bond after N-tert-butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C-C bonds through cleavage of the C-N bond using non-precious metal catalysis. PMID- 26673266 TI - A threading receptor for polysaccharides. AB - Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (K(a) up to 19,000 M(-1)), and is shown--by nuclear Overhauser effect spectroscopy--to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules. PMID- 26673269 TI - Water Protects Graphitic Surface from Airborne Hydrocarbon Contamination. AB - The intrinsic wettability of graphitic materials, such as graphene and graphite, can be readily obscured by airborne hydrocarbon within 5-20 min of ambient air exposure. We report a convenient method to effectively preserve a freshly prepared graphitic surface simply through a water treatment technique. This approach significantly inhibits the hydrocarbon adsorption rate by a factor of ca. 20*, thus maintaining the intrinsic wetting behavior for many hours upon air exposure. Follow-up characterization shows that a nanometer-thick ice-like water forms on the graphitic surface, which remains stabilized at room temperature for at least 2-3 h and thus significantly decreases the adsorption of airborne hydrocarbon on the graphitic surface. This method has potential implications in minimizing hydrocarbon contamination during manufacturing, characterization, processing, and storage of graphene/graphite-based devices. As an example, we show that a water-treated graphite electrode maintains a high level of electrochemical activity in air for up to 1 day. PMID- 26673268 TI - A supramolecular helix that disregards chirality. AB - The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks. PMID- 26673277 TI - How to avoid the anger of ghosts. PMID- 26673276 TI - THE EFFECTS OF ANTICIPATION ON THE MECHANICS OF THE KNEE DURING SINGLE-LEG CUTTING TASKS: A SYSTEMATIC REVIEW. AB - BACKGROUND: ACL injuries are common in sports, which has resulted in the development of risk screening and injury prevention programs to target modifiable neuromuscular risk factors. Previous studies which have analyzed single-leg cutting tasks have reported that the anticipation status of the task (pre-planned vs. unanticipated) has a significant effect on the mechanics of the knee. HYPOTHESIS/PURPOSE: The purpose of this systematic review is to assess the effect of anticipation on the mechanics of the knee in the sagittal, frontal, and transverse planes during tasks which athletes frequently perform during competition. STUDY DESIGN: Systematic Review. METHODS: The following databases were searched using relevant key words and search limits: Pub Med, SPORTDiscus, CINAHL, and Web of Science. A modified version of the Downs and Black checklist was used to assess the methodological quality of the articles by two independent reviewers. RESULTS: 284 articles were identified during the initial database search. After a screening process, 34 articles underwent further review. Of these articles, 13 met the criteria for inclusion in this systematic review. CONCLUSIONS: It appears that tasks which do not allow a subject to pre-plan their movement strategy promote knee mechanics which may increase an athlete's risk of injury. CLINICAL RELEVANCE: Clinicians involved in the development and implementation of ACL injury risk screening and prevention programs may want to consider incorporating tasks which do not allow time for pre-planning. These unanticipated tasks may more closely mimic the demands of the sports environment and may promote mechanics which increase the risk of injury. LEVEL OF EVIDENCE: Level 1b. PMID- 26673278 TI - Complete Series of Alkali-Metal M(BH3NH2BH2NH2BH3) Hydrogen-Storage Salts Accessed via Metathesis in Organic Solvents. AB - We report a new efficient way of synthesizing high-purity hydrogen-rich M(BH3NH2BH2NH2BH3) salts (M = Li, Na, K, Rb, Cs). The solvent-mediated metathetic synthesis applied here uses precursors containing bulky organic cations and weakly coordinating anions. The applicability of this method permits the entire series of alkali-metal M(BH3NH2BH2NH2BH3) salts (M = Li, Na, K, Rb, Cs) to be obtained, thus enabling their comparative analysis in terms of crystal structures and hydrogen-storage properties. A novel polymorphic form of Verkade's base (C18H39N4PH)(BH3NH2BH2NH2BH3) precursor was also characterized structurally. For all compounds, we present a comprehensive structural, spectroscopic, and thermogravimetric characterization (PXRD, NMR, FTIR, Raman, and TGA/DSC/MS). PMID- 26673279 TI - Outcome of therapeutic penetrating keratoplasty in a tertiary eye care center in Nepal. AB - BACKGROUND: Corneal ulcer is an important cause of blindness in developing countries. Therapeutic keratoplasty for infective keratitis is a frequently performed surgery in these countries. OBJECTIVE: To find out the outcome of therapeutic keratoplasty for infective keratitis. METHODS: Records of 5 years were reviewed of patients who underwent therapeutic keratoplasty from 2006 to 2010. Data collected included demographic parameters, indications for surgery, microbiology of the ulcers, type of surgery performed, and donor tissue details. In the follow-up period, ocular status was evaluated in terms of eradication of disease, anatomic success, graft clarity, visual acuity, and development of glaucoma and cataract. RESULTS: In all, 180 eyes of 180 patients were enrolled in the study; 59.4% of the patients were male. Average age was 44.4+/-16.7 years. Overall, 71% of infective keratitis was perforated. A total of 101 (56%) eyes were positive for organisms of which 49 showed pure fungus and 49 showed pure bacteria. The commonest fungus and bacteria isolated were Aspergillus and Streptococcus, respectively. Average follow-up period was 29+/-23 months. Overall cure rate of infection was 88.8%, anatomical success rate was 89.5%, and graft clarity was 37.2%. Overall, 43.4% had secondary glaucoma. In the postoperative course, 65.8% of phakic eyes had developed cataract. In all, 38.6% of graft had endothelial failure and 24% of the graft failed due to late infective keratitis. Overall functional success with a visual acuity above 6/60 was 25.4%. Bacterial keratitis had a significantly higher cure rate, anatomical success, and graft clarity compared to fungal keratitis. CONCLUSION: Therapeutic keratoplasty is an important procedure to save the eye and preserve vision in severe infective keratitis. There is a high incidence of postoperative glaucoma, cataract, and graft failure in such a surgery. Bacterial keratitis has a better outcome than fungal keratitis. PMID- 26673280 TI - Pancytopenia in Multiple Myeloma- An Enigma: Our Experience from Tertiary Care Hospital. AB - INTRODUCTION: Multiple myeloma is a plasma cell neoplasm that is characterized by clonal proliferation of malignant plasma cell in the bone marrow along with M protein in the serum and/or urine. Pancytopenia as a initial presentation of multiple myeloma is quite unusual. We are presenting a case series having pancytopenia as the presenting complaint. MATERIALS AND METHODS: A retrospective study was conducted for a period of 30 months, wherein all the cases of multiple myeloma presenting with pancytopenia were included. The complete blood picture, peripheral smear examination, bone marrow aspirate & protein electrophoresis of all the cases were reviewed & analysed. RESULTS: During the study period, 10 cases presented with pancytopenia with a mean age of 66.3 years (range: 59-72 years) at presentation with male: female ratio being 8:2. Fatigue and weakness was the most common symptom (100%) & average ESR was 104 mm/hour. High-resolution serum electrophoresis, showed a dense, sharp to wide M band in the gamma globulin region. Bone marrow plasma cell percentage was increased with an average of 63.1%. Bone marrow biopsy correlation was obtained in 100% cases. CONCLUSION: Diagnosing multiple myeloma, presenting as pancytopenia requires a high degree of suspicion to avoid delay in initiation of treatment. PMID- 26673281 TI - The Characteristics of Effective Cancer Education Media Interventions among African Americans: A Systematic Review. AB - Cancer incidence and mortality is a significant area of health disparity between African Americans and Caucasians. In the current article the authors used a systematic review design to examine the characteristics of different cancer media education intervention (CMEI) to increase access to cancer screenings for African Americans within a 30 year period (1980-2010). Ten computerized databases were searched using inclusion-exclusion criteria. Consequently, 179 potential studies were identified, and later reduced to 41 eligible studies through the inclusion exclusion criteria. The eligible studies had a combined sample size of N = 12,764 respondents. The findings revealed that multi-media intervention strategies were the most common media intervention that led to increased cancer screenings among African Americans. The authors conclude with a call for social workers to be more involved in developing and following up with culturally appropriate media strategies that can increase the likelihood of early detection and successful treatment, thus reducing this important area of health disparity. PMID- 26673282 TI - Sonography of abdominal organs in precocious puberty in girls. AB - Precocious puberty constitutes a significant clinical problem due to psychological implications and health concerns as well as consequences associated with girls' fertility. Self-acceptance, peer approval, early motherhood and future fertility - these are only a few issues associated with puberty, the disorders of which may have a negative influence on personality and health. The role of imaging is to determine the causes of early activation of the puberty process, to identify lesions responsible for abnormal sex hormone production and those which are the result of underlying hormonal disorders as well as to diagnose the processes which only mimic symptoms of precocious puberty. Out of all available imaging methods, sonography, thanks to its safety, availability and low cost, seems to be the best method to assess the breasts and internal organs of patients manifesting symptoms of precocious puberty both in early diagnosis and follow-up examinations. Apart from the technique of performing ultrasound examinations, the paper also explains its role in precocious puberty in girls, describes correct parameters of the organs which play the most significant role in the process of puberty as well as presents the features of changes responsible for or resulting from hormonal disorders. PMID- 26673283 TI - Peritonectomy procedures and HIPEC in the treatment of peritoneal carcinomatosis from ovarian cancer: Long-term outcomes and perspectives from a high-volume center. AB - BACKGROUND: Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) represents a radical therapeutic approach to achieve complete cytoreduction in ovarian peritoneal carcinomatosis. The aim of the present study was to analyze the outcomes obtained by the application of these procedures in a single center with extensive experience treating peritoneal carcinomatosis. PATIENTS AND METHODS: A series of 218 consecutive patients diagnosed with peritoneal carcinomatosis from primary or recurrent ovarian cancer (FIGO stage IIIC-IV) and treated with CRS + HIPEC between January 1996 and June 2012 were included in this observational study. RESULTS: Peritoneal carcinomatosis was treated primarily in 56% (124/218) of the cases and recurrently in 43% (94/218). A total of 42/218 patients (19%) presented with FIGO stage IV. Compared to recurrent cases, patients with primary ovarian carcinomatosis were older and presented higher Peritoneal Cancer Index (PCI) and percentage of FIGO stage IV; however, no significant differences in survival (5 year overall survival in patients with R0 cytoreduction, 63% and 56%, respectively) were observed. Cytoreduction score, PCI, lymphatic involvement and surgical morbidity >=Grade III were statistically significant prognostic factors for survival in both univariate and multivariate analysis. CONCLUSIONS: CRS + HIPEC treating macroscopic and microscopic disease is currently an excellent surgical approach to achieve high rates of complete cytoreduction and improve survival in patients with peritoneal carcinomatosis from ovarian cancer. In order to minimize the high potential morbidity of these procedures, CRS + HIPEC should be performed in highly experienced centers. PMID- 26673284 TI - Retrobulbar blood flow and visual organ function disturbance in the course of giant cell arteritis coexisting with optic disc drusen - a case report. AB - The review presented ophthalmologic syndrome connected with visual organ function disorder in giant cell arteritis patient concomitant with optic nerve disc drusen. Diagnostic difficulties were shown in relation to incidence of both similar ophthalmic symptoms as well as interpretation of specialists examinations results (pattern visual evoked potential test, scanning laser polarimetry, and perimetric tests - kinetic and static). Apart from ophthalmic investigations, significant role of radiological examinations was considered, especially color Doppler ultrasonography of retrobulbar circulation - optic artery, central retinal artery, long posterior ciliary arteries. Adequate interpretation of results seems to be crucial to establish scheme and timing of treatment in case of co-occurrence of the abovementioned disorders. In the presented case early implementation of steroid therapy resulted in improvement of blood flow parameters and the regression of ophthalmological complaints. Visual field deficiency in kinetic perimetry, reduced wave amplitude p100 in visual evoked potential test as well as decrease in number of optic nerve fibers in optic nerve disc region in scanning laser polarimetry exam can be diagnostic features in diagnosis of visual impairment in the course of giant cell arteritis and optic nerve disc drusen. Evaluation of blood flow velocity parameters in retrobulbar arteries in color Doppler ultrasonography is the most valuable screening in monitoring ophthalmic dysregulation in presented disorders. PMID- 26673285 TI - Answer to the question from page 117. PMID- 26673291 TI - [Immunocorrection in combined prevention of early postoperative complications in patients with systemic vasculitis]. AB - The authors studied peculiarities of the immune status in angiosurgical patients with systemic vasculitis, as well as possibilities of immunodiagnosis and immunocorrection in prevention of early coagulopathic and reparative complications after angiosurgical interventions in this cohort of patients. A total of 172 angiosurgical patients presenting with systemic vasculitis were subdivided into two groups depending on the preoperative preparation methods used. In Group One (Study Group) comprising 81 patients preoperative preparation was carried out using immunosuppressive therapy with hormones and cytostatics according to the rheumatologist's indications. In Group Two (n=91) hormones and/or cytostatics were replaced by the proposed four-component immunocorrection including various combinations of correcting the lifestyle, use of antioxidative activity immunomodulators, plasmapheresis and intravenous administration of immunoglobulins. It was determined that using this method of correction made it possible to achieve a good anti-inflammatory effect in angiosurgical patients with systemic vasculitis, thus avoiding negative aftermaths of immunosuppression. The developed method of immunocorrection makes it possible to decrease the rate of early postoperative coagulopathic and reparative complications in angiosurgical patients as compared to therapy with hormones and/or cytostatics. PMID- 26673292 TI - [Results of comprehensive management of patients with chronic lower limb ischaemia using gene-engineering technologies of angiogenesis stimulation (Part 2)]. AB - Presented herein are the results of clinical use of gene engineering methods of stimulating angiogenesis in patients with lower limb chronic ischaemia. An open prospective controlled clinical study included a total of 160 patients with lower limb chronic ischaemia. Gene engineering technologies of angiogenesis stimulation were used both as an independent method of treatment in comprehensive conservative therapy (80 patients) and as comprehensive treatment in combination with revascularizing operations (80 patients). Part Two of the article deals with the results of using the above technologies in the composition of comprehensive treatment. It was shown that gene-engineering technologies of angiogenesis stimulation may successfully be used in comprehensive conservative treatment in patients with stage IIB CLLI, as well as stage III. Clinically meaningful improvement is confirmed by objective factors, including better parameters of regional haemodynamics, perfusion, functional reserve of blood flow, etc. Gene engineering methods of angiogenesis stimulation were found demonstrated were associated with good tolerance and an admissible rate of adverse events in patients with CLLI. All undesirable events turned out transitory during the immediate follow-up period. PMID- 26673286 TI - Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis. AB - The conventional photosensitizers used in photodynamic therapy (PDT), such as haematoporphyrin (HP), have not yet reached satisfactory therapeutic effects on port-wine stains (PWSs), due largely to the long-term dark toxicity. Previously we have showed that hypericin exhibited potent photocytotoxic effects on Roman chicken cockscomb model of PWSs. However, the molecular mechanism of hypericin mediated photocytotoxicity remains unclear. In this study, we employed human umbilical vein endothelial cells (HUVECs) to investigate the hypericin-photolytic mechanism. Our study showed that hypericin-PDT induced reactive oxygen species (ROS), resulting in cell killings and an activation of the inflammatory response. Importantly, we have also discovered that photoactivated hypericin induced apoptosis by activating the mitochondrial caspase pathway and inhibiting the activation of the vascular endothelial growth factor-A (VEGF-A)-mediated PI3K/Akt pathway. Notably, we found that hypericin exhibited a more potent photocytotoxic effect than HP, and largely addressed the inconvenience issue associated with the use of HP. Thereby, hypericin may be a better alternative to HP in treating PWSs. PMID- 26673294 TI - [Multispiral computed tomography in diagnosis of vascular pathology in patients with nonspecific aortoarteritis]. AB - Multispiral computed tomography in the angiographic mode is relatively a new method in diagnosis of arterial lesions in patients presenting with nonspecific aortoarteritis. With virtually no contraindications to carrying out the examination, this method makes it possible to obtain an exclusively clear-cut picture of the vascular bed in both two- and three-dimensional projection, to correlate it with osseous structures. This method of diagnosis may also be used for dynamic follow up of patients in the postoperative period. PMID- 26673293 TI - [Treatment of patients with acute lower limb ischaemia: selective thrombolysis or open surgical interventions?]. AB - The study was aimed at bettering therapeutic outcomes in patients with acute arterial lower-limb insufficiency by means of improving the method of selective thrombolysis (STL). We analyzed both immediate and remote results of treating a total of 118 patients presenting with acute lower limb ischaemia of not more than grade 2B (according to I.I. Zatevakhin, 2002) within the terms up to 2 months from the onset of the disease. The Study Group patients (n=67) were subjected to STL and the Control Group patients (n=51) underwent standard open surgical interventions. The remote results of treatment were assessed within the terms up to 1 year in 38 patients of the Study Group and in 31 patients of the Control Group. The main criteria for efficacy of treatment were the incidence rate of amputation and mortality. In the immediate postoperative period in the Control Group, the frequency of amputations of lower limbs was more than 5-fold higher as compared with the Study Group (p<0.005); no significant differences on lethal outcomes were revealed (p>0.05). In the remote period of follow up, the incidence of amputations in the Study and Control Groups did not statistically differ (p>0.05), whereas mortality in Control Group was 4.3-fold higher as compared with the Study Group (p<0.05). PMID- 26673295 TI - [Monitoring of the state of the proximal portion of thrombus in conservative treatment of patients with varicothrombophlebitis]. AB - Ultrasound duplex scanning (USD) was used to study dynamics of the state of the proximal portion of the thrombus in patients presenting with acute varicothrombophlebitis of saphenous veins during conservative treatment. We examined a total of fifty-four 29-to-78-year-old (mean age 53.5 years) patients with acute varicothrombophlebitis of saphenous veins, including 15 (27.8%) men and 39 (72.2%) women. USD was used to determine: localization and extent of thrombosis, proximal level of the thrombus, presence of the free portion of the thrombus, density and structure of the proximal and distal portion of the thrombus, thickness of the inflamed venous wall and paravasal fat at the level of the proximal and distal portions of the thrombus. Twelve (22.2%) patients were found to have signs of thrombus flotation with high embologenic risk; these patients underwent the operation of Troyanov-Trendelenburg and were excluded from the study. The remaining 42 patients received conservative treatment and were dynamically followed up by means of USD. All patients on the background of comprehensive conservative treatment showed positive dynamics consisting in decreased mass and density of the thrombus, shift of its proximal border in the distal direction, decreased thickness of the inflamed venous wall and paravasal fat. Two variants of dynamics were singled out: relatively rapid (during a week) group 1 (n=11) and relatively slow (during one month) - group 2 (n=31). It was determined that the most significant factors promoting rapid lysis of the proximal portion of the thrombus were as follows: the term of seeking medical attention (duration of thrombosis), low echogenicity of the thrombus, cellular pattern of the thrombus and thickness of the paravasal fat. A conclusion was drawn that monitoring of the state of the proximal portion of the thrombus by means of USD makes it possible to maximally approach solving the problem of individualized treatment of patients with thrombosis of saphenous veins. PMID- 26673296 TI - [Scintigraphic assessment of alterations in cardiopulmonary haemodynamics and renal functional activity in patients with endured coronary artery bypass grafting]. AB - OBJECTIVE: By means of scintigraphic methods to assess alterations in cardiopulmonary haemodynamics and renal functional activity in patients with coronary artery disease (CAD) after endured coronary artery bypass grafting (CABG) performed in conditions of extracorporeal circulation (EC) and on the functioning heart. MATERIAL AND METHODS: We examined a total of 40 patients presenting with CAD (mean age 54.90+/-1.12 years) after endured CABG. All patients were subdivided into 2 groups: Group One consisting of 20 patients subjected to CABG performed on the beating heart with the use of myocardial "stabilizer" "Acrobat" (Study Group) and Group Two also comprising 20 patients but undergoing surgery with the use of extracorporeal circulation (Comparison Group). All patients included into the study were subjected to radiocardiopulmonography with (99m)Tc-pertechnetate and dynamic radionuclide renoscintigraphy with (99m)Tc-DTPA before and 6-7 days after operative treatment. RESULTS: In the early postoperative period after CABG, the patients of the both groups were found to have a significant increase in the minute volume, cardiac index, and circulation efficiency coefficient, accompanied by a significant decrease in the period of half-emptying of the left ventricle, thus suggesting improvement of LV contractility. Improved pulmonary microcirculation resulting from operative treatment in the compared groups of patients was confirmed by significantly shortened time of the indicator's passing through pulmonary vessels at the expense of both arterial (TAM) and venous (TVM) components. At the same time, a decrease in these parameters in the Study Group patients was more pronounced as compared with the Comparison Group patients. Thus, the means of the difference between the pre- and postoperative values of TAM and TVM in the Study Group amounted to 1.78 +/- .40 s and 1.78 +/- 0.32 s, and in the Comparison Group to 0.95 +/- 0.22 s and 0.98 +/- 0.16 s, respectively (p=0.029 and p=0.031 for TAM and TVM, respectively). The Comparison Group patients after CABG were found to have a significant decrease in the mean values of the total glomerular filtration rate (GFR) in combination with decelerated clearance of the indicator from blood. 30% of patients under the effect of nonpulsating blood flow developed relatively pronounced renal dysfunction (a decrease in the total GFR and/or GRF of one of the kidneys by 15% and more as compared with the initial level). Besides, these patients also demonstrated significant changes in the half-clearance of the radiopharmaceutical from the renal parenchyma and the index of cortical retention of the indicator on the both sides. Unlike the Comparison Group, in patients without EC the average values of the majority of parameters of renal filtration activity underwent no statistically significant alterations as compared with the baseline (prior to CABG) values. CONCLUSION: Coronary artery bypass grafting without cardiac arrest exerts less pronounced negative influence upon the state of the renal function as compared with the open-heart surgery with extracorporeal circulation, which may partially be conditioned by statistically more significant positive dynamics of microcirculation in the system of pulmonary circulation under the effect of myocardial revascularization with the use of the myocardial stabilizer "off-pump". PMID- 26673297 TI - [Endoprosthetic repair of the abdominal aorta in patients with infrarenal aneurysm and unfavourable anatomy of its proximal neck]. AB - Analysed herein are immediate and remote results of endoprosthetic repair of the abdominal aorta in patients with unfavourable anatomy of its proximal neck. Group I (Study Group) was composed of 31 patients with unfavourable anatomy of the proximal neck, the control group (Group II) comprised a total of 52 patients with no unfavourable anatomical factors. The criteria of assessment were as follows: technical success, adequate position of the endograft, frequency of the development of various endoleaks, duration of the operation and hospital stay, lethality in the remote period, and necessity of secondary interventions. Technical success of endoprosthetic repair was achieved in 100% of patients in the both groups. An adequate position by the proximal end of the coated portion of the endograft was observed in 27 (87.1%) patients of Group I and in 51 (98.1%) patients of the control group (p=0.08). Secondary postdilatation of the endograft's body in the proximal neck was statistically more often performed in the study group of patients. The duration of the operation and hospital stay in the compared groups had no statistically significant differences. In the remote period, patients with unfavourable morphology of the proximal neck were found to develop type I-A endoleaks into the cavity of the aneurysm. By other evaluated criteria such as the total survival rate, secondary interventions, graft migration, type I-B, II and V endoleaks no statistically significant differences were revealed. It was concluded that endoprosthetic repair of the abdominal aorta in patients with unfavourable anatomy of the proximal neck of the aneurysm is associated with admissible immediate, short- and long-term outcomes. Longer follow up is required in order to more adequately asses the reliability of the obtained findings. PMID- 26673298 TI - [Open stenting of thoracic aorta in combination with the borst operation]. AB - Described herein in is a clinical case report concerning combined method of surgical treatment for chronic DeBakey type I aortic dissection: prosthetic repair of the ascending aorta and aortic arch according to Borst's technique in combination with open stenting of the descending aorta with the "Djumbodis" uncoated metal stent. This technique makes it possible to achieve expanding of the vascular prosthesis in the descending portion, thus increasing the probability of thrombosis of the false channel at this level and, consequently, to decrease the probability of further dilatation of the thoracic aorta, which is one of the main purposes in aortic reconstruction. Besides, the use of this technique does not exclude a second stage of surgical treatment, both within the framework of the classical surgical technology and with the use of endovascular methods. PMID- 26673299 TI - [Experience with the ovations stent graft system for totally percutaneous endovascular repair of the infrarenal portion of the abdominal aorta]. AB - Presented in the article are clinical cases of successful totally percutaneous endovascular repair of the infrarenal portion of the abdominal aorta using the Ovation Prime ultra-low profile stent graft in high-surgical-risk patients, yielding good immediate and short-term results, thus demonstrating new possibilities in endovascular treatment of aneurysms of the infrarenal portion of the abdominal aorta. PMID- 26673300 TI - [Use of thrombolytic therapy and rheolytic thrombectomy in treatment of pulmonary artery thromboembolism]. AB - The article deals with the results of combined treatment of patients with pulmonary thromboembolism by means of systemic thrombolytic therapy, anticoagulant therapy, and rheolytic thrombectomy during the period from 2012 to 2013. Thrombolytic therapy was used in 78 of 187 patients with the confirmed diagnosis of pulmonary thromboembolism (Group 1). The diagnosis was verified and therapeutic results were controlled by means of contrast-enhanced spiral computed tomography and perfusion scintigraphy. Thrombolysis was carried out using: tissue plasminogen activator - alteplase (61 cases) with administration of the full dose during 2 hours, streptokinase (14 cases) at a dose of 1.5 million IU in the mode of prolonged infusion during 24 hours and urokinase (3 cases) at a dose of 4400 IU/kg during 12 hours. 109 patients were subjected to anticoagulant therapy (Group 2). Five patients were subjected to rheolytic thrombectomy for desobstruction of the pulmonary artery. The method was used in patients with previously performed ineffective or partially effective thrombolytic therapy, as well as in patients with contraindications to thrombolysis. The lethality rate for TLT amounted to 5.4% and that for anticoagulant therapy 26.6%. Probability of a lethal outcome in Group 2 (anticoagulant therapy) turned out to be 6.71 times higher as compared with Group 1 (thrombolytic therapy). In all cases of using rheolytic thrombectomy we managed to achieve a decrease of the Miller index and systolic pressure in the pulmonary artery. Desobstruction of the pulmonary artery was complete in 3 cases. In two cases rheolytic thrombectomy was partially effective and the patients underwent repeat thrombolysis with a good clinical outcome. Using systemic thrombolysis in patients with pulmonary artery thromboembolism demonstrated a positive effect on the prognosis of survival. Rheolytic thrombectomy contributed to improvement of the results of thrombolytic therapy and may be used as an alternative method of treatment. PMID- 26673301 TI - [Postoperative relapses of varicose disease]. AB - Analysed herein are the results of examining and treating a total of 290 patients presenting with relapses of varicose disease, including 198 women and 92 men. The patients' age averaged 51.6 +/- 8.7 years, with the mean term of the appearance of relapses after surgery amounting to 4.8 +/- 1.4 years and that of reoperation 11.1 +/- 7.5 years. According to the CEAP classification, the patients were subdivided as follows: C2 - 36 (12.4 %), S3 - 117 (40.4 %), S4 - 103 (35.5 %), S5 - 20 (6.9 %), S6 - 14 (4.8 %). All patients underwent ultrasound duplex scanning. Relapses in the basin of the great saphenous vein were revealed in 205 (70.63 %) patients, in the basin of the small saphenous vein in 65 (22.4 %) subjects. Neoangiogenesis was observed in 62 (21.3 %) cases, pathological reflux from pelvic veins as a cause of relapses - in 31 (10.7 %) patients, varicosity-altered tributaries of the great and small saphenous veins, not connected with the pathological stump or unremoved trunk - in 52 (17.9 %) cases. Based on the results of diagnosis, treatment was carried out in 241 patients. 179 patients underwent various types of interventions, of these, 94 with the use of minimally invasive therapeutic technologies. 76 patients were subjected to different methods of phlebosclerosing treatment, of these 62 in outpatient conditions. The study showed negative influence of axial reflux along through deep veins on the appearance and course of varicose veins relapses. The remote results of treatment at terms from one year to 9 years (mean 4.9 +/- 2.6 years) were studied in 76 patients. Good results were noted in 52 (68.5 %) patients, satisfactory outcomes were observed in 22 (28.9 %), and unsatisfactory results - in 2 (2.6 %) patients. PMID- 26673302 TI - [Results of ultrasound-guided foam sclerotherapy of the great saphenous vein according to the improved technique]. AB - Foam sclerotherapy is an innovative method of treatment for varicose disease, including its truncal forms, making it possible in outpatient conditions to achieve favourable therapeutic and cosmetic outcomes. Analysed herein are the results of foam sclerotherapy of the great saphenous vein (GSV) and its tributaries in a total of 326 patients presenting with varicose disease of lower limbs (395 GSVs) according to the improved methodology (elevation of the extremity to 60 degrees , crural bandage, use of a cooled sclerosant solution). 6 14 days after the first session of sclerotherapy, the control ultrasound examination confirmed occlusion of the GSV in its femoral segment with no reflux in 94.9% of cases (375 GSVs). At terms from 1 year to 5 years, occlusion was diagnosed in 91.1% of cases. Besides alterations in the ultrasound image of the venous superficial bed of the limb and reduction of the trunk of the GSV and its affluents, there was positive dynamics of the clinical symptomatology of the disease. PMID- 26673303 TI - [Pathogenesis and prevention of secondary thromboses and thromboembolic complications in patients with endured lower limb deep vein thrombosis]. AB - The study was aimed at revealing the role of thrombophilic states in the pathogenesis of deep vein thrombosis and determining efficacy of pathogenetic prevention of venous thromboembolic complications. The study included a total of 84 patients presenting with lower limb deep vein thrombosis. The patients were subdivided into two groups. The patients of the Study Group (n=44) were examined for thrombophilic states, revealing of which was followed by prescribing specific lifelong therapy aimed at correction of the alterations revealed. The Control Group patients (n=40) received a carefully selected therapeutic dose of warfarin (until the value of the International Normalized Ratio was within the therapeutic range from 2 to 3) and were given recommendations on taking this agent for 6 months followed by discontinuation. The Study Group patients demonstrated less relapses of deep vein thromboses as compared with the Control Group patients. The symptoms of chronic venous insufficiency in the Study Group were also less pronounced. These results are in accord with the findings of ultrasonographic duplex scanning in the remote period after endured thrombosis. A conclusion was drawn on the necessity of carrying out further studies aimed at altering the recommended therapeutic regimen for patients in the remote period after sustained deep vein thrombosis. PMID- 26673304 TI - [Diagnostic peculiarities, surgical policy, and efficacy of reconstructive operations in pathological tortuosity of internal carotid arteries]. AB - We examined a total of 88 patients presenting with unilateral pathological tortuosity of internal carotid arteries (PT ICA), who were subjected to reconstructive interventions. The patients underwent ultrasound duplex scanning of brachiocephalic arteries, CT angiography of the brain, and assessment of cognitive functions according to the Montreal scale (MoCA test). It was proved that absolute indications for operative intervention in patients with pathological tortuosity of ICA comprise coiling, and in kinking - an increase in the linear blood velocity greater than 180 cm/s. Perfusion CT makes it possible to objectively assess the state of blood supply to the cerebral hemispheres. CT angiography of ICAs with 3D reconstruction makes it possible to reveal microaneurysms of the vascular wall in the area of pathological tortuosity. PT leads to deficit of cognitive functions, and performing reconstructive operations improves cognitive functions after 6 months in stage III chronic cerebrovascular insufficiency in 91% of cases, and in stage IV - in 55%. PMID- 26673305 TI - [Fasciotomy as a method of surgical preparation of a conduit for coronary artery bypass grafting]. AB - The study included a total of 59 patients undergoing coronary artery bypass grafting with the use of the radial artery (RA). Group One consisted of 28 patients who while preparing the conduit were subjected to longitudinal dissection of the fascial compartment (fasciotomy) of the RA. Group Two comprised 31 patients not undergoing fasciotomy. In Group One patients prior to fasciotomy, 2 segments were cut off from each RA and incubated in a hypo osmotic solution either in the fascial compartment (n=28) or after fasciotomy (n=28) followed by morphometric analysis. Therapeutic results in all patients were studied averagely 3.3 +/- 0.8 years after surgery. 32 patients underwent control coronary bypass angiography averagely 2.5 +/- 0.54 years after the operation. The morphometric analysis of the RA segments in conditions of simulated oedema revealed that a more pronounced decrease in the RA lumen (by 49.7%) was observed in the segments kept in the fascial compartment as compared with the segments after fasciotomy (1.08 +/- 0.12 mm and 2.21 +/- 0.09 mm, respectively, p=0.0129). In the remote period after the operation (mean 3.3 +/- 0.8 years) Group One patients were found to have fewer cases of renewal and increase of the angina class (n=3; 10.7%) than Group Two patients (n=7; 22.5%; p=0.0289). There were no cases of secondary myocardial infarction in Group One patients, whereas in Group Two there were 2 (6.5%) cases of myocardial infarction in the postoperative period. Based on the findings of coronary bypass angiography, patency of the RA in Group 1 was higher than in Group 2 (91.6 and 78.6%, respectively; p=0.0371). The obtained results are suggestive that fasciotomy of the RA during surgical preparation of the conduit is appropriate, thus decreasing the risk of blood flow reduction via the arterial bypass graft and improving the outcomes of autoarterial coronary bypass grafting. PMID- 26673306 TI - [Reconstructive operations in pathology of central veins, associated with vascular approach]. AB - Presented herein are the results of treatment of 28 patients with stenosis/occlusion of central veins undergoing replacement therapy by means of programmed haemodialysis for terminal renal failure. The clinical symptomatology in all patients manifested itself by chronic lymphovenous insufficiency of the upper limb, dysfunction of the vascular access (14 patients, thrombosis of the vascular approach (5 patients), venous hypertension of the brain (4 patients). 17 patients had aneurysms of the vascular approach in the zone of puncture. In 18 cases for correction of the venous outflow we performed roentgenoendovascular angioplasty, including 3 cases in combination with stenting. Technical success amounted to 83.3% (15 of 18 cases). 13 patients underwent open reconstructive operations, including 5 cases of thrombectomy from the vein (in all cases failed one), in 8 cases bypassing operations (cross cephalic anterior jugular shunting - 5, subclavian-femoral bypass grafting - 1, transposition of the external jugular vein into the internal jugular vein - 1. In-hospital patency of bypasses amounted to 87.5% (7 shunts of 8). The remote results were followed up within the terms up to 43 months (averagely 12.3 +/- 2.2 months). In the group of endovascular treatment more than half of patients (8 of 15) required secondary endovascular interventions. The cumulative requirements in re-do manipulations amounted to 52.4% during the first year and to 89.4% during the second year. The function of the approach was preserved in 93.3% of patients. Of the seven shunts patent in the early postoperative period, occlusion occurred in three cases at 1, 5 and 13 months. The 1-year patency amounted to 50.0%. The function of the approach was preserved in 75.0% of cases. PMID- 26673308 TI - [Use of self-expandable stent grafts in aneurysms of internal carotid arteries]. AB - Open surgical intervention is an operation of choice in lesions of coronary arteries. In some cases, however, performing reconstructive surgery is either impossible or associated with high risk of both intra- and postoperative complications. In such cases it is possible to perform an endovascular intervention, including endoprosthetic repair. The Russian and foreign literature contains either sporadic or small-in-number case reports concerning the use of stent grafts in carotid arteries aneurysms. The article describes cases of successful use of self-expandable stent grafts in three patients with a true aneurysm and pseudoaneurysms of internal carotid arteries. PMID- 26673307 TI - [Effect of extracellular matrix components on adhesion of bone marrow multipotent mesenchymal stromal cells to polytetrafluoroethylene]. AB - Search for new bioengineering materials for creation of small-diameter vascular grafts is currently a priority task. One of the promising trends of creating tissue engineering constructions is coating the internal layer of implants made of polytetrafluoroethylene (PTFE) with autologous mesenchymal multipotent stromal cells. In the study we assessed the ability of separate components of the extracellular matrix such as fibronectin, type I collagen and type IV collagen to influence adhesion, proliferation and morphology of mesenchymal multipotent stromal cells being cultured on PTFE. Bone marrow multipotent stromal cells taken from second-passage Wistar rats in the amount of 106 per 1 cm2 were applied onto PTFE. We used the following variants of preliminary treatment of the material prior to seeding: fibronectin with type I collagen, fibronectin with type IV collagen, fibronectin with a mixture of type I and IV collagens, as well as a control group without coating. After six weeks of cell growth on PTFE patches the samples were subjected to fixation in 10% formalin followed by haematoxylin-eosin stain and morphometric assessment of adhered cells by calculation using the software AxioVision (Carl Zeiss), assessing the number of cells, area of the cellular monolayer, dimensions and ratios of the area of separate cells and the area of cellular nuclei. The maximal area of the monolayer from mesenchymal multipotent stromal cells on the PTFE surface was revealed while culturing with a mixture of fibronectin and type I and IV collagens. Cell colonization density while treatment of the synthetic material with mixtures of fibronectin with type I collagen, type IV collagen and type I and IV collagens demonstrated the results exceeding the parameters of the control specimen 5-, 2.5- and 7-fold, respectively. Hence, extracellular matrix components considerably increase enhance adhesion of cells to PTFE, as well as improve formation of a monolayer from mesenchymal multipotent stromal cells. PMID- 26673309 TI - [State of the carotid artery bifurcation after surgery involving the use of absorbable suture material]. AB - The authors present herein a clinical case report assessing the state of the carotid artery bifurcation zone while performing secondary operation for restenosis 7 years after the primary operation (eversion carotid endarterectomy). The redo operation was carried out using absorbable suture material during anastomosis formation. This suture material used in arterial reconstructions turned out to result in good reparation of the anastomosis, not inducing coarse deformity of the vascular wall, thus in the long run making it possible to simplify the course of the redo operation. PMID- 26673310 TI - [Possibilities of hybrid surgery in treatment of thoracoabdominal aneurysms]. AB - The authors present a clinical case report and review of literature concerning treatment of extremely complicated pathology - thoracoabdominal aortic aneurysm, also reflecting the most difficult problems and complications of classical surgical treatment. A successful clinical example showed advantages of a new, less invasive approach, i.e., hybrid surgery. Based on analysing literature sources, the authors describe controversial points of carrying out a hybrid operation and its results. Accumulating experience in and improving technology of the hybrid operation would make it possible to further improve therapeutic outcomes. PMID- 26673311 TI - High-speed extra-intracranial bypass combined with an assisting low-speed anastomosis: surgical technique and a clinical example. AB - Described herein is the technique of performing assisting low-speed and high speed extra-intracranial bypass, followed by a clinical case report concerning successful application of this technique in trapping of a giant aneurysm of the cavernous portion of the internal carotid artery in a female patient after endured transitory ischaemic attack during the test with temporary balloon mediated occlusion of the internal carotid artery. PMID- 26673312 TI - Screening for and Estimating the Prevalence of Essential Tremor: A Random-Digit Dialing-Based Study in the New York Metropolitan Area. AB - BACKGROUND: There are nearly no published screening instruments for essential tremor (ET). This is a remarkable fact, given its high prevalence. Here, we assess the validity of a screening questionnaire and hand-drawn spirals and also estimate the prevalence of ET in a community sample. METHODS: Four hundred nineteen study subjects living in a geographically defined area in the New York metropolitan area were contacted using a random digit telephone dialing scheme. Seven tremor screening questions were administered and each subject drew 2 spirals. A movement disorders neurologist assigned ET diagnoses based on neurological examination. RESULTS: The spirals were a more sensitive test than the screening questions (73.7 vs. 26.3%); specificities of the 2 tests were similar (95.5 vs. 96.8%). The combination of both tests was not superior to the use of spirals alone. The positive predictive value of the spiral test was 43.8%. The crude prevalence of ET, 19 of 419 (4.53%, 95% CI 2.92-6.97), increased with age (p = 0.049). CONCLUSIONS: A screening spiral was more sensitive than a screening questionnaire for ET and was moderately sensitive. Nearly one-half of subjects who screened positive had ET; therefore, when screening a population, one can expect the number of true positives and false positives to be roughly equivalent. PMID- 26673313 TI - Facet Energy and Reactivity versus Cytotoxicity: The Surprising Behavior of CdS Nanorods. AB - Responsible development of nanotechnology calls for improved understanding of how nanomaterial surface energy and reactivity affect potential toxicity. Here, we challenge the paradigm that cytotoxicity increases with nanoparticle reactivity. Higher-surface-energy {001}-faceted CdS nanorods (CdS-H) were less toxic to Saccharomyces cerevisiae than lower-energy ({101}-faceted) nanorods (CdS-L) of similar morphology, aggregate size, and charge. CdS-H adsorbed to the yeast's cell wall to a greater extent than CdS-L, which decreased endocytosis and cytotoxicity. Higher uptake of CdS-L decreased cell viability and increased endoplasmatic reticulum stress despite lower release of toxic Cd(2+) ions. Higher toxicity of CdS-L was confirmed with five different unicellular microorganisms. Overall, higher-energy nanocrystals may exhibit greater propensity to adsorb to or react with biological protective barriers and/or background constituents, which passivates their reactivity and reduces their bioavailability and cytotoxicity. PMID- 26673314 TI - The correspondence and collaboration of Harvey Cushing and Irvine Page: Lessons from the Cleveland Clinic Archives. AB - Harvey Cushing is well-known as a pioneer of brain surgery and is considered the father of modern neurosurgery. However, Cushing's interests and contributions extend beyond neurosurgery. Through his determined interdisciplinary collaboration in medicine and biomedical research, Cushing was able to contribute to numerous fields including bacteriology, anesthesiology, and endocrinology. With regards to the latter, Cushing corresponds with Irvine Page, well-known for isolating serotonin, discovering the renin-angiotensin system, and postulating of the mosaic theory of hypertension. In a correspondence spanning 3 years, from January 1933 to April 1936, Cushing and Page collaborated to discover a substance responsible for hypertension. In this historical article, the authors review the letters to highlight the collaborative efforts between leaders in disparate fields driven by the scientific curiosity. As national research agencies are focusing their funds toward collaborative and interdisciplinary research, it is interesting to note the historical communication among the scientific leaders that led to discoveries in the respective fields. PMID- 26673315 TI - Nursing Academic Administrators' Lived Experiences With Incivility and Bullying From Faculty: Consequences and Outcomes Demanding Action. AB - There are an increasing number of nursing academic administrators who identify themselves as victims of faculty incivility. This study examined experiences that academic administrators encountered with faculty incivility using a phenomenological research design. Three major themes emerged: faculty inappropriate behaviors, consequences of faculty behaviors on administrator targets, and administrators call for action. Findings revealed that incivility had devastating effects on administrators personally and professionally. PMID- 26673316 TI - Twitter: An Application to Encourage Information Seeking Among Nursing Students. AB - Twitter is a social networking application that has seen limited evaluation in nursing education. The aim of this study was to determine if Twitter could be used to stimulate further exploration about current clinical and professional topics with nurse practitioner students. The students used Twitter to receive tweets on clinical and professional topics from the instructor throughout the semester: 75% demonstrated willingness to follow the links in the tweets to seek more information, and 87% expressed a desire to receive the tweets even after the semester was over. PMID- 26673317 TI - A Differential Item Functional Analysis by Age of Perceived Interpersonal Discrimination in a Multi-racial/ethnic Sample of Adults. AB - We investigated whether individual items on the nine item William's Perceived Everyday Discrimination Scale (EDS) functioned differently by age (<45 vs >= 45) within five racial groups in the United States: Asians (n=2,017); Hispanics (n=2,688); Black Caribbeans (n=1,377); African Americans (n=3,434); and Whites (n=854). We used data from the 2001-2003 National Survey of American Lives and the 2001-2003 National Latino and Asian Studies. Multiple-indicator, multiple cause models (MIMIC) were used to examine differential item functioning (DIF) on the EDS by age within each racial/ethnic group. Overall, Asian and Hispanic respondents reported less discrimination than Whites; on the other hand, African Americans and Black Caribbeans reported more discrimination than Whites. Regardless of race/ethnicity, the younger respondents (aged <45 years) reported less discrimination than the older respondents (aged >= 45 years). In terms of age by race/ethnicity, the results were mixed for 19 out of 45 tests of DIF (40%). No differences in item function were observed among Black Caribbeans. "Being called names or insulted" and others acting as "if they are afraid" of the respondents were the only two items that did not exhibit differential item functioning by age across all racial/ethnic groups. Overall, our findings suggest that the EDS scale should be used with caution in multi-age multi-racial/ethnic samples. PMID- 26673318 TI - Ultrasound elastography for imaging tendons and muscles. AB - Ultrasound elastography is a recently developed ultrasound-based method which allows the qualitative or quantitative evaluation of the mechanical properties of tissue. Strain (compression) ultrasound elastography is the commonest technique performed by applying mild compression with the hand-held transducer to create real-time strain distribution maps, which are color-coded and superimposed on the B-mode images. There is increasing evidence that ultrasound elastography can be used in the investigation of muscle, tendon and soft tissue disease in the clinical practice, as a supplementary tool to conventional ultrasound examination. Based on preliminary data, potential clinical applications include early diagnosis, staging, and guiding interventions musculotendinous and neuromuscular disease as well as monitoring disease during rehabilitation. Ultrasound elastography could also be used for research into the biomechanics and pathophysiology of musculotendinous disease. Despite the great interest in the technique, there is still limited evidence in the literature and there are several technical issues which limit the reproducibility of the method, including differences in quantification methods, artefacts, limitations and variation in the application of the technique by different users. This review presents the published evidence on musculoskeletal applications of strain elastography, discusses the technical issues and future perspectives of this method and emphasizes the need for standardization and further research. PMID- 26673319 TI - USP7 Is a Suppressor of PCNA Ubiquitination and Oxidative-Stress-Induced Mutagenesis in Human Cells. AB - Mono-ubiquitinated PCNA activates error-prone DNA polymerases; therefore, strict regulation of PCNA mono-ubiquitination is crucial in avoiding undesired mutagenesis. In this study, we used an in vitro assay system to identify USP7 as a deubiquitinating enzyme of mono-ubiquitinated PCNA. Suppression of USP1, a previously identified PCNA deubiquitinase, or USP7 increased UV- and H2O2-induced PCNA mono-ubiquitination in a distinct and additive manner, suggesting that USP1 and USP7 make different contributions to PCNA deubiquitination in human cells. Cell-cycle-synchronization analyses revealed that USP7 suppression increased H2O2 induced PCNA ubiquitination throughout interphase, whereas USP1 suppression specifically increased ubiquitination in S-phase cells. UV-induced mutagenesis was elevated in USP1-suppressed cells, whereas H2O2-induced mutagenesis was elevated in USP7-suppressed cells. These results suggest that USP1 suppresses UV induced mutations produced in a manner involving DNA replication, whereas USP7 suppresses H2O2-induced mutagenesis involving cell-cycle-independent processes such as DNA repair. PMID- 26673321 TI - Distinct Pores for Peroxisomal Import of PTS1 and PTS2 Proteins. AB - Two peroxisomal targeting signals, PTS1 and PTS2, recognized by cytosolic receptors Pex5 and cooperating Pex7/Pex18, direct folded proteins to the peroxisomal matrix. A pore consisting of the PTS1 receptor Pex5 and the docking protein Pex14 imports PTS1 proteins. We identified a distinct PTS2-specific pore, which contains the PTS2 co-receptor Pex18 and the Pex14/Pex17-docking complex as major constituents. The estimated maximal pore size of ~ 4.7 nm is large enough to allow import of folded PTS2 proteins. PTS2 cargo proteins modulate complex gating, open probability, and subconductance states of the pore. While the PTS1 channel is transiently activated by arriving receptor-cargo complexes, the reconstituted PTS2 channel is constitutively present in an open state. However, the cargo-loaded PTS2 channel is largely impermeable to solutes and ions. Our results demonstrate that import of PTS1 and PTS2 proteins does not converge at the peroxisomal membrane as previously anticipated but is performed by distinct pores. PMID- 26673320 TI - Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux. AB - Calcium signaling has long been associated with key events of immunity, including chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium flux in motile immune cells in live animals remain challenging. Using light-sheet microscopy for in vivo calcium imaging in zebrafish, we observe characteristic patterns of calcium flux triggered by distinct events, including phagocytosis of pathogenic bacteria and migration of neutrophils toward inflammatory stimuli. In contrast to findings from ex vivo studies, we observe enriched calcium influx at the leading edge of migrating neutrophils. To directly manipulate calcium dynamics in vivo, we have developed transgenic lines with cell specific expression of the mammalian TRPV1 channel, enabling ligand-gated, reversible, and spatiotemporal control of calcium influx. We find that controlled calcium influx can function to help define the neutrophil's leading edge. Cell specific TRPV1 expression may have broad utility for precise control of calcium dynamics in other immune cell types and organisms. PMID- 26673322 TI - Cell-Autonomous Ca(2+) Flashes Elicit Pulsed Contractions of an Apical Actin Network to Drive Apical Constriction during Neural Tube Closure. AB - Neurulation is a critical period in all vertebrates and results in the formation of the neural tube, which gives rise to the CNS. Apical constriction is one of the fundamental morphogenetic movements that drives neural tube closure. Using live imaging, we show that apical constriction during the neurulation is a stepwise process driven by cell-autonomous and asynchronous contraction pulses followed by stabilization steps. Our data suggest that contraction events are triggered by cell-autonomous Ca(2+) flashes and are driven by a transient contractile apical pool of actin. In addition, we provide evidence that the cell autonomy and asynchrony of contraction are required for the correct spatial distribution of constriction and, as a result, are critical for tissue morphogenesis. Finally, we identify Calpain2 as a regulator of apical constriction and show that it is required for the stabilization step, but is dispensable during contraction. PMID- 26673323 TI - The Histone Demethylase KDM5 Activates Gene Expression by Recognizing Chromatin Context through Its PHD Reader Motif. AB - KDM5 family proteins are critically important transcriptional regulators whose physiological functions in the context of a whole animal remain largely unknown. Using genome-wide gene expression and binding analyses in Drosophila adults, we demonstrate that KDM5 (Lid) is a direct regulator of genes required for mitochondrial structure and function. Significantly, this occurs independently of KDM5's well-described JmjC domain-encoded histone demethylase activity. Instead, it requires the PHD motif of KDM5 that binds to histone H3 that is di- or trimethylated on lysine 4 (H3K4me2/3). Genome-wide, KDM5 binding overlaps with the active chromatin mark H3K4me3, and a fly strain specifically lacking H3K4me2/3 binding shows defective KDM5 promoter recruitment and gene activation. KDM5 therefore plays a central role in regulating mitochondrial function by utilizing its ability to recognize specific chromatin contexts. Importantly, KDM5 mediated regulation of mitochondrial activity is likely to be key in human diseases caused by dysfunction of this family of proteins. PMID- 26673324 TI - Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA. AB - Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by a polyglutamine expansion in the androgen receptor (AR) and is associated with misfolding and aggregation of the mutant AR. We investigated the role of an interdomain interaction between the amino (N)-terminal FxxLF motif and carboxyl (C)-terminal AF-2 domain in a mouse model of SBMA. Male transgenic mice expressing polyQ-expanded AR with a mutation in the FxxLF motif (F23A) to prevent the N/C interaction displayed substantially improved motor function compared with N/C-intact AR-expressing mice and showed reduced pathological features of SBMA. Serine 16 phosphorylation was substantially enhanced by the F23A mutation; moreover, the protective effect of AR F23A was dependent on this phosphorylation. These results reveal an important role for the N/C interaction on disease onset in mice and suggest that targeting AR conformation could be a therapeutic strategy for patients with SBMA. PMID- 26673325 TI - Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and beta Cell Failure. AB - Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic beta cell mass and function is unclear. Here, we reveal that mice lacking beta cell OGT (betaOGT-KO) develop diabetes and beta cell failure. betaOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of beta cell mass due to ER-stress induced apoptosis and decreased proliferation. Akt1/2 signaling was also dampened in betaOGT-KO islets. The mechanistic role of these processes was demonstrated by rescuing the phenotype of betaOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. These findings identify OGT as a regulator of beta cell mass and function and provide a direct link between O-GlcNAcylation and beta cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. PMID- 26673329 TI - Prtl99C Acts Together with Protamines and Safeguards Male Fertility in Drosophila. AB - The formation of motile spermatozoa involves the highly conserved formation of protamine-rich, tightly packed chromatin. However, genetic loss of protamine function in Drosophila and mice does not lead to significant decompaction of sperm chromatin. This indicates that other proteins act redundantly or together with protamines. Here, we identify Prtl99C as a Drosophila sperm chromatin associated protein that is essential for male fertility. Whereas the loss of protamines results in modest elongation of sperm nuclei, knockdown of Prtl99C has a much stronger effect on sperm nuclei. Loss of protamines and Prtl99C indicates an additive effect of these proteins on chromatin compaction, in agreement with independent loading of these factors into sperm chromatin. These data reveal that at least three chromatin-binding proteins act together in chromatin reorganization to compact the paternal chromatin. PMID- 26673328 TI - Differential DNA Methylation Analysis without a Reference Genome. AB - Genome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for DNA methylation analysis in non-model organisms, we developed an integrated approach for studying DNA methylation differences independent of a reference genome. Experimentally, our method relies on an optimized 96-well protocol for reduced representation bisulfite sequencing (RRBS), which we have validated in nine species (human, mouse, rat, cow, dog, chicken, carp, sea bass, and zebrafish). Bioinformatically, we developed the RefFreeDMA software to deduce ad hoc genomes directly from RRBS reads and to pinpoint differentially methylated regions between samples or groups of individuals (http://RefFreeDMA.computational-epigenetics.org). The identified regions are interpreted using motif enrichment analysis and/or cross-mapping to annotated genomes. We validated our method by reference-free analysis of cell type-specific DNA methylation in the blood of human, cow, and carp. In summary, we present a cost-effective method for epigenome analysis in ecology and evolution, which enables epigenome-wide association studies in natural populations and species without a reference genome. PMID- 26673327 TI - The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. AB - Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2 induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers. PMID- 26673330 TI - Ethical Perspective: Five Unacceptable Trade-offs on the Path to Universal Health Coverage. AB - This article discusses what ethicists have called "unacceptable trade-offs" in health policy choices related to universal health coverage (UHC). Since the fiscal space is constrained, trade-offs need to be made. But some trade-offs are unacceptable on the path to universal coverage. Unacceptable choices include, among other examples from low-income countries, to expand coverage for services with lower priority such as coronary bypass surgery before securing universal coverage for high-priority services such as skilled birth attendance and services for easily preventable or treatable fatal childhood diseases. Services of the latter kind include oral rehydration therapy for children with diarrhea and antibiotics for children with pneumonia. The article explains why such trade-offs are unfair and unacceptable even if political considerations may push in the opposite direction. PMID- 26673331 TI - A Global Social Support System: What the International Community Could Learn From the United States' National Basketball Association's Scheme for Redistribution of New Talent. AB - If global trade were fair, it is argued, then international aid would be unnecessary and inequalities inherent to the economic system would be justifiable. Here, we argue that while global trade is unfair, in part because richer countries set the rules, we believe that additional interventions must go beyond trade regulation and short-term aid to redress inequalities among countries that will persist and possibly worsen in spite of such measures. Drawing on an example of measures taken to redress the characteristics of a system that inherently increases inequality, the ability of dominant teams in the National Basketball Association (NBA) to recruit the most talented players, we argue that market-based competition even in the context of fair rules will create and amplify economic inequalities. We argue that, just as the NBA created a draft to reduce the emergence of severe inequalities among teams, systems of social support within richer countries should be paralleled by a global system to counterbalance persisting inequalities among countries that are produced by market forces. We explain how such a mechanism might operate among integrated market economies, and identify the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) as an example of such an emerging form of global social support. PMID- 26673326 TI - Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells. AB - To identify therapeutic targets for glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 knockout (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers). In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, most likely as a result of oncogenic signaling, causing GBM-specific lethality. PMID- 26673332 TI - Setting Healthcare Priorities at the Macro and Meso Levels: A Framework for Evaluation. AB - BACKGROUND: Priority setting in healthcare is a key determinant of health system performance. However, there is no widely accepted priority setting evaluation framework. We reviewed literature with the aim of developing and proposing a framework for the evaluation of macro and meso level healthcare priority setting practices. METHODS: We systematically searched Econlit, PubMed, CINAHL, and EBSCOhost databases and supplemented this with searches in Google Scholar, relevant websites and reference lists of relevant papers. A total of 31 papers on evaluation of priority setting were identified. These were supplemented by broader theoretical literature related to evaluation of priority setting. A conceptual review of selected papers was undertaken. RESULTS: Based on a synthesis of the selected literature, we propose an evaluative framework that requires that priority setting practices at the macro and meso levels of the health system meet the following conditions: (1) Priority setting decisions should incorporate both efficiency and equity considerations as well as the following outcomes; (a) Stakeholder satisfaction, (b) Stakeholder understanding, (c) Shifted priorities (reallocation of resources), and (d) Implementation of decisions. (2) Priority setting processes should also meet the procedural conditions of (a) Stakeholder engagement, (b) Stakeholder empowerment, (c) Transparency, (d) Use of evidence, (e) Revisions, (f) Enforcement, and (g) Being grounded on community values. CONCLUSION: Available frameworks for the evaluation of priority setting are mostly grounded on procedural requirements, while few have included outcome requirements. There is, however, increasing recognition of the need to incorporate both consequential and procedural considerations in priority setting practices. In this review, we adapt an integrative approach to develop and propose a framework for the evaluation of priority setting practices at the macro and meso levels that draws from these complementary schools of thought. PMID- 26673333 TI - Comparison of Blood Transfusion Plus Chelation Therapy and Bone Marrow Transplantation in Patients with beta-Thalassemia: Application of SF-36, EQ-5D, and Visual Analogue Scale Measures. AB - BACKGROUND: beta-Thalassemia is a prevalent genetic disease in Mediterranean countries. The most common treatments for this disease are blood transfusion plus iron chelation (BTIC) therapy and bone marrow transplantation (BMT). Patients using these procedures experience different health-related quality of life (HRQoL). The purpose of the present study was to measure HRQoL in these patients using 2 different multiattribute quality of life (QoL) scales. METHODS: In this cross-sectional study, data were gathered using 3 instruments: a socio demographic questionnaire, EQ-5D, and SF-36. A total of 196 patients with beta thalassemia were randomly selected from 2 hospitals in Shiraz (Southern Iran). Data were analyzed using logistic regression and multiple regression models to identify factors that affect the patients' HRQoL. RESULTS: The average EQ-5D index and EQ visual analog scale (VAS) scores were 0.86 (95% CI: 0.83-0.89) and 71.85 (95% CI: 69.13-74.58), respectively. Patients with BMT reported significantly higher EQ VAS scores (83.27 vs 68.55, respectively). The results showed that patients who lived in rural area and patients with BMT reported higher EQ VAS scores (rural; beta= 10.25, P = .006 and BMT; beta= 11.88, P = .000). As well, SF-36 between 2 groups of patients were statistically significant in physical component scale (PCS). CONCLUSION: Patients in the BMT group experienced higher HRQoL in both physical and mental aspects compared to those in the BTIC group. More studies are needed to assess the relative cost-effectiveness of these methods in developing countries. PMID- 26673334 TI - Shaping the Health Policy Agenda: The Case of Safe Motherhood Policy in Vietnam. AB - BACKGROUND: Maternal health remains a central policy concern in Vietnam. With a commitment to achieving the Millennium Development Goal (MDG) 5 target of maternal mortality rate (MMR) of 70/100 000 by 2015, the Ministry of Health (MoH) issued the National Plan for Safe Motherhood (NPSM) 2003-2010. In 2008, reproductive health, including safe motherhood (SM) became a national health target program with annual government funding. METHODS: A case study of how SM emerged as a political priority in Vietnam over the period 2001-2008, drawing on Kingdon's theory of agenda-setting was conducted. A mixed method was adopted for this study of the NPSM. RESULTS: Three related streams contributed to SM priority in Vietnam: (1) the problem of high MMR was officially recognized from high quality research, (2) the strong roles of policy champion from MoH in advocating for the needs to reducing MMR as well as support from government and donors, and (3) the national and international events, providing favorable context for this issue to emerge on policy agenda. CONCLUSION: This paper draws on the theory of agenda-setting to analyze the Vietnam experience and to develop guidance for SM a political priority in other high maternal mortality communities. PMID- 26673335 TI - Health Literacy Impact on National Healthcare Utilization and Expenditure. AB - BACKGROUND: Health literacy presents an enormous challenge in the delivery of effective healthcare and quality outcomes. We evaluated the impact of low health literacy (LHL) on healthcare utilization and healthcare expenditure. METHODS: Database analysis used Medical Expenditure Panel Survey (MEPS) from 2005-2008 which provides nationally representative estimates of healthcare utilization and expenditure. Health literacy scores (HLSs) were calculated based on a validated, predictive model and were scored according to the National Assessment of Adult Literacy (NAAL). HLS ranged from 0-500. Health literacy level (HLL) and categorized in 2 groups: Below basic or basic (HLS <226) and above basic (HLS >=226). Healthcare utilization expressed as a physician, nonphysician, or emergency room (ER) visits and healthcare spending. Expenditures were adjusted to 2010 rates using the Consumer Price Index (CPI). A P value of 0.05 or less was the criterion for statistical significance in all analyses. Multivariate regression models assessed the impact of the predicted HLLs on outpatient healthcare utilization and expenditures. All analyses were performed with SAS and STATA(r) 11.0 statistical software. RESULTS: The study evaluated 22 599 samples representing 503 374 648 weighted individuals nationally from 2005-2008. The cohort had an average age of 49 years and included more females (57%). Caucasian were the predominant racial ethnic group (83%) and 37% of the cohort were from the South region of the United States of America. The proportion of the cohort with basic or below basic health literacy was 22.4%. Annual predicted values of physician visits, nonphysician visits, and ER visits were 6.6, 4.8, and 0.2, respectively, for basic or below basic compared to 4.4, 2.6, and 0.1 for above basic. Predicted values of office and ER visits expenditures were $1284 and $151, respectively, for basic or below basic and $719 and $100 for above basic (P < .05). The extrapolated national estimates show that the annual costs for prescription alone for adults with LHL possibly associated with basic and below basic health literacy could potentially reach about $172 billion. CONCLUSION: Health literacy is inversely associated with healthcare utilization and expenditure. Individuals with below basic or basic HLL have greater healthcare utilization and expendituresspending more on prescriptions compared to individuals with above basic HLL. Public health strategies promoting appropriate education among individuals with LHL may help to improve health outcomes and reduce unnecessary healthcare visits and costs. PMID- 26673336 TI - Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands. AB - Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children <=18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries. PMID- 26673337 TI - Adaptive Policies for Reducing Inequalities in the Social Determinants of Health. AB - Inequalities in the social determinants of health (SDH), which drive avoidable health disparities between different individuals or groups, is a major concern for a number of international organisations, including the World Health Organization (WHO). Despite this, the pathways to changing inequalities in the SDH remain elusive. The methodologies and concepts within system science are now viewed as important domains of knowledge, ideas and skills for tackling issues of inequality, which are increasingly understood as emergent properties of complex systems. In this paper, we introduce and expand the concept of adaptive policies to reduce inequalities in the distribution of the SDH. The concept of adaptive policy for health equity was developed through reviewing the literature on learning and adaptive policies. Using a series of illustrative examples from education and poverty alleviation, which have their basis in real world policies, we demonstrate how an adaptive policy approach is more suited to the management of the emergent properties of inequalities in the SDH than traditional policy approaches. This is because they are better placed to handle future uncertainties. Our intention is that these examples are illustrative, rather than prescriptive, and serve to create a conversation regarding appropriate adaptive policies for progressing policy action on the SDH. PMID- 26673338 TI - Is It Possible to Develop a Compassionate Organization? Comment on "Why and How Is Compassion Necessary to Provide Good Quality Healthcare?". AB - This paper represents a commentary to Marianna Fotaki's Editorial: 'Why and how is compassion necessary to provide good quality healthcare?' Within this commentary, I discuss some of the issues raised by Marianna Fotaki, and conclude that we should work towards an organizational culture which considers the important concept of compassion by focusing on the well-being and teamwork of all involved. PMID- 26673339 TI - Why and How Is Compassion Necessary to Provide Good Healthcare? Comments From an Academic Physician Comment on "Why and How Is Compassion Necessary to Provide Good Quality Healthcare?". AB - This is a short commentary to the editorial issued by Marianna Fotaki, entitled: "Why and how is compassion necessary to provide good quality healthcare." It introduces the necessity of a more cognitive approach to explore further the determinants of behavior towards compassionate care. It raises questions about the importance of training towards a more patient-care and values driven healthcare system. PMID- 26673340 TI - Training for Better Management: Avante Zambezia, PEPFAR and Improving the Quality of Administrative Services Comment on "Implementation of a Health Management Mentoring Program: Year-1 Evaluation of Its Impact on Health System Strengthening in Zambezia Province, Mozambique". AB - The United States President's Emergency Plan for AIDS Relief (PEPFAR) emphasizes health systems strengthening as a cornerstone of programmatic success. Health systems strengthening, among other things, includes effective capacity building for clinical care, administrative management and public health practice. Avante Zambezia is a district-level in-service training program for administrative staff. It is associated with improved accounting practices and human resources and transportation management but not monitoring and evaluation. We discuss other examples of successful administrative training programs that vary in the proportion of time that is spent learning on the job and the proportion of time spent in classrooms. We suggest that these programs be more rigorously evaluated so that lessons learned can be generalized to other countries and regions. PMID- 26673341 TI - Management Certainly Matters, and There Are Multiple Ways to Conceptualize the Process Comment on "Management Matters: A Leverage Point for Health Systems Strengthening in Global Health". AB - The authors of "Management matters: a leverage point for health systems strengthening in global health," raise a crucial issue. Because more effective management can contribute to better performing health systems, attempts to strengthen health systems require attention to management. As a guide toward management capacity building, the authors outline a comprehensive set of core management competencies needed for managing global health efforts. Although, I agree with the authors' central premise about the important role of management in improving global health and concur that focusing on competencies can guide management capacity building, I think it is important to recognize that a set of relevant competencies is not the only way to conceptualize and organize efforts to teach, learn, practice, or conduct research on management. I argue the added utility of also viewing management as a set of functions or activities as an alternative paradigm and suggest that the greatest utility could lie in some hybrid that combines various ways of conceptualizing management for study, practice, and research. PMID- 26673342 TI - The Health Mobility Is All True Mobility? Comment on "Regional Incentives and Patient Cross-border Mobility: Evidence From the Italian Experience". AB - In their study, Brenna and Spandonaro analyzed the mobility into Italian regions. In particular, it analyzes the situation of 5 regions, with very different backgrounds. With this paper, we try to better define the meaning of health mobility and to find its underlying causes. Furthermore, we propose a strategy that could help in controlling mobility flows that currently are the source of health inequalities. PMID- 26673343 TI - Can a Healthcare "Lean Sweep" Deliver on What Matters to Patients? Comment on "Improving Wait Times to Care for Individuals with Multimorbidities and Complex Conditions Using Value Stream Mapping". AB - Disconnects and defects in care - such as duplication, poor integration between services or avoidable adverse events - are costly to the health system and potentially harmful to patients and families. For patients living with multiple chronic conditions, such disconnects can be particularly detrimental. Lean is an approach to optimizing value by reducing waste (eg, duplication and defects) and containing costs (eg, improving integration of services) as well as focusing on what matters to patients. Lean works particularly well to optimize existing processes and services. However, as the burden of chronic illness and frailty overtake episodic care needs, health systems require far greater complex, adaptive change. Such change ought to take into account outcomes in population health in addition to care experiences and costs (together, comprising the Triple Aim); and involve patients and families in co-designing new models of care that better address complex, longer-term health needs. PMID- 26673344 TI - It Is Not That Simple nor Compelling! Comment on "Translating Evidence Into Healthcare Policy and Practice: Single Versus Multi-faceted Implementation Strategies - Is There a Simple Answer to a Complex Question?". AB - Healthcare decisions are often made under pressure, with varying levels of information in a changing clinical context. With limited resources and a focus on improving patient outcomes, healthcare managers and health professionals strive to implement both clinical and cost-effective care. However, the gap between research evidence and health policy/clinical practice persists despite our best efforts. In an attempt to close the gap through behaviour change interventions, there has been a strong held belief that 'more is better,' without understanding the mechanisms and circumstances of knowledge translation (KT). We argue that even a single intervention or strategy in translating evidence into healthcare policy or practice is rarely simple to implement. Nor is the evidence compelling on the best approach. As Harvey and Kitson argued, designing and evaluating KT interventions requires flexibility and responsiveness. If we are to move forward in translation science then we need to use rigorous designs such as randomised controlled trials to test effectiveness of interventions or strategies with embedded process evaluations to understand the reason interventions do or do not work! PMID- 26673345 TI - Achieving a "Grand Convergence" in Global Health by 2035: Rwanda Shows the Way Comment on "Improving the World's Health Through the Post-2015 Development Agenda: Perspectives From Rwanda". AB - Global Health 2035, the report of The Lancet Commission on Investing in Health, laid out a bold, highly ambitious framework for making rapid progress in improving global public health outcomes. It showed that with the right health investments, the international community could achieve a "grand convergence" in global health-a reduction in avertable infectious, maternal, and child deaths down to universally low levels-within a generation. Rwanda's success in rapidly reducing such deaths over the last 20 years shows that convergence is feasible. Binagwaho and Scott have argued that 5 lessons from this success are the importance of equity, quality health services, evidence-informed policy, intersectoral collaboration, and effective collaboration between countries and multilateral agencies. This article re-examines these lessons through the lens of the Global Health 2035 report to analyze how the experience in Rwanda might be generalized for other countries to making progress towards achieving a grand convergence. PMID- 26673346 TI - Health Management Mentoring for Health Systems Strengthening: A Response to Recent Commentaries. PMID- 26673347 TI - Clinical and Pathological Evaluation of Mycobacterium marinum Group Skin Infections Associated With Fish Markets in New York City. AB - BACKGROUND: From December 2013 through May 2014, physicians, dermatopathologists, and public health authorities collaborated to characterize an outbreak of Mycobacterium marinum and other nontuberculous mycobacterial skin and soft tissue infections (SSTIs) associated with handling fish in New York City's Chinatown. Clinicopathologic and laboratory investigations were performed on a series of patients. METHODS: Medical records were reviewed for 29 patients. Culture results were available for 27 patients and 24 biopsy specimens were evaluated by histopathology, immunohistochemistry (IHC) staining for acid-fast bacilli (AFB), and mycobacterial polymerase chain reaction (PCR) assays. RESULTS: All patients received antibiotics. The most commonly prescribed antibiotic regimen was clarithromycin and ethambutol. Of the 29 patients in this case series, 16 (55%) received surgical treatment involving incision and drainage, mass excision, and synovectomy. Of these, 7 (44%) had deep tissue involvement. All patients showed improvement. For those with culture results, 11 of 27 (41%) were positive for M. marinum; the remainder showed no growth. Poorly formed granulomas (96%), neutrophils (75%), and necrosis (79%) were found in 24 biopsies. Of 15 cases that were culture-negative and analyzed by other methods, 9 were PCR positive for M. marinum group species, 8 were IHC positive, and 3 were positive by AFB stains. CONCLUSIONS: A multidisciplinary approach was used to identify cases in an outbreak of M. marinum infections. The use of histopathology, culture, and IHC plus PCR from full thickness skin biopsy can lead to improved diagnosis of M. marinum SSTIs compared to relying solely on mycobacterial culture, the current gold standard. PMID- 26673348 TI - A Combination Strategy of Ceftriaxone, Sulbactam and Disodium Edetate for the Treatment of Multi-Drug Resistant (MDR) Septicaemia: A Retrospective, Observational Study in Indian Tertiary Care Hospital. AB - INTRODUCTION: Previous studies have suggested the use of rational combination therapy for the treatment of multi-drug resistant (MDR) infections. An antibiotic adjuvant entity (AAE) of ceftriaxone, sulbactam and disodium edetate (Elores) was approved for multi-drug resistant infections in India. AIM: This study was designed to investigate the efficacy and safety of this AAE in patients with sepsis due to extended spectrum beta lactamse (ESBL) and metallo-beta lactamase (MBL) producing pathogens. MATERIALS AND METHODS: A retrospective observational study was conducted in patients admitted in intensive care unit (ICU) at tertiary health care site in India, with enrollment from 24 March, 2012 to 7 Aug, 2012. Patients eligible for enrollment had clear infection of bacterial septicaemia, were aged 12-65 years, and were considered for treatment with Cephalosporins categories of antibiotics. RESULTS: Total 18 patients were included in the study and all assigned to combination of ceftriaxone, sulbactam and disodium edetate. Complete clinical cure in terms of relief and no-disease symptoms had observed in 15 (83.3%) subjects, however 3 (16.6%) showed treatment failure (TF). Similarly for bacteriological eradication response, 15 (83.3%) patients displayed complete bacteriological eradication response and 03 (16.6%) subjects showed TF. No serious side effect was observed during the study. CONCLUSION: This study recommends the use of combination of ceftriaxone, sulbactam and disodium edetate (EDTA) for the treatment of MDR septicaemia associated with ESBL and MBL producing microbes. PMID- 26673349 TI - Recent advances in the field of anti-cancer immunotherapy. AB - BACKGROUND: The main goal of anti-cancer therapy is to specifically inhibit the malignant activity of cancer cells, while leaving healthy cells unaffected. As such, for every proposed therapy, it is important to keep in mind the therapeutic index - the ratio of the toxic dose over the therapeutic dose. The use of immunotherapy has allowed a means to both specifically block protein-protein interaction and deliver cytotoxic events to a tumor-specific antigen. REVIEW SCOPE: It is the objective of this review to give an overview on current immunotherapy treatment for cancers using monoclonal antibodies. We demonstrate three exciting targets for immunotherapy, TNF-alpha Converting Enzyme (TACE), Cathepsin S and Urokinase Plasmogen Activator and go over the advances made with one of the most used monoclonal antibodies in cancer therapy, Rituximab; as well as Herceptin, which is used for breast cancer therapy. Furthermore, we touch on other venues of immunotherapy, such as adaptive cell transfer, the use of nucleic acids and the use of dendritic cells. Finally, we summarize some ongoing studies that spell tentative advancements for anti-cancer immunotherapy. GENERAL SIGNIFICANCE: Immunotherapy is at the forefront of anti-cancer therapies, allying both a high degree of specificity to general high effectiveness and fewer side effects. PMID- 26673350 TI - Effect of paracentesis on metabolic activity in patients with advanced cirrhosis and ascites. AB - OBJECTIVE: Patients with decompensated cirrhosis often suffer from malnutrition. To enable appropriate nutritional supplementation a correct estimation of resting energy expenditure (REE) is needed. It is, however, unclear whether the volume of ascites should be included or not in the calculations of the REE. MATERIAL AND METHODS: In 19 patients with cirrhosis and ascites, measurements of REE by indirect calorimetry were performed before paracentesis, after paracentesis, and four weeks after paracentesis. Moreover, handgrip strength (HGS), dual X-ray absorptiometry (DXA), and biochemistry were assessed. RESULTS: Calculated and measured REE differed more than 10% in 63% of the patients at baseline. By including the weight of ascites in the calculation of REE, the REE was overestimated by 283 (-602-1381) kJ/day (p = 0.69). By subtracting the weight of ascites in the calculation of REE, it was underestimated by -379 (-1915 - 219) kJ/day, (p = 0.06). Patients in whom measured REE decreased after paracentesis had higher middle arterial pressure (MAP) (p = 0.02) and p-sodium (p = 0.02) at baseline. Low HGS (M: <30 kg; W < 20 kg) was evident in 68% of the patients. T scores revealed osteopenia and osteoporosis in 58% and 16%, respectively. Reduced vitamin D levels (<50 nmol/l) were found in 68%. CONCLUSIONS: The presence of ascites seems to increase REE, why we suggest that when REE is calculated, the weight of ascites should be included. Indirect calorimetry is, however, preferable for REE estimation. More than two-third of patients with ascites suffer from muscle weakness and/or osteopenia. PMID- 26673351 TI - Paving the way to nanoionics: atomic origin of barriers for ionic transport through interfaces. AB - The blocking of ion transport at interfaces strongly limits the performance of electrochemical nanodevices for energy applications. The barrier is believed to arise from space-charge regions generated by mobile ions by analogy to semiconductor junctions. Here we show that something different is at play by studying ion transport in a bicrystal of yttria (9% mol) stabilized zirconia (YSZ), an emblematic oxide ion conductor. Aberration-corrected scanning transmission electron microscopy (STEM) provides structure and composition at atomic resolution, with the sensitivity to directly reveal the oxygen ion profile. We find that Y segregates to the grain boundary at Zr sites, together with a depletion of oxygen that is confined to a small length scale of around 0.5 nm. Contrary to the main thesis of the space-charge model, there exists no evidence of a long-range O vacancy depletion layer. Combining ion transport measurements across a single grain boundary by nanoscale electrochemical strain microscopy (ESM), broadband dielectric spectroscopy measurements, and density functional calculations, we show that grain-boundary-induced electronic states act as acceptors, resulting in a negatively charged core. Besides the possible effect of the modified chemical bonding, this negative charge gives rise to an additional barrier for ion transport at the grain boundary. PMID- 26673353 TI - Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus associated gastric cancer. AB - BACKGROUND: This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS: Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917 25.525, P = 0.063). CONCLUSION: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC. PMID- 26673354 TI - Silica Ouzo Effect: Amphiphilic Drugs Facilitate Nanoprecipitation of Polycondensed Mercaptosilanes. AB - Amphiphilic drugs are therapeutic agents whose molecular structures contain both hydrophobic and hydrophilic portions. Here we report a systematic study on how amphiphilic drugs can assist in silica nanoprecipitation. 3 Mercaptopropyltrimethoxysilane (MPTMS) was used as the sole silica material and 12 amphiphilic drugs spanning a wide spectrum of therapeutic categories were included. MPTMS polycondensation was conducted in a DMSO-based organic phase. After a sufficient time, particle formation was induced by injecting a small amount of the organic phase into a water solution containing various amphiphiles. The results show that all amphiphilic drugs studied exerted concentration dependent facilitating effect on nanoparticle formation. Under certain preparation conditions, the particle solution showed physical stability over a long period and the formed particles could be as small as 100 nm. By systematically varying drug concentrations and injection volumes, the ability of each amphiphile to promote nanoprecipitation can be quantified and compared, based on two novel indices: the area under the critical volume-concentration curve (AUC) and the critical stabilization concentration (CSC). We demonstrate that both ability indices significantly correlated with the drug's log P and critical micelle concentrations (CMC). Furthermore, we have optimized the aging and particle purification condition and extensively characterized our system through comprehensive TEM and zeta-potential measurements, as well as determinations for drug entrapment and release. In conclusion, we have established a quantitative structure-activity relationship for amphiphilic small molecular drugs in their ability to interact with poly(mercaptopropyl)silsesquioxane species and form nanoparticles via solvent shifting. We speculate that both hydrophobic and electrostatic interactions play important roles in the formation and stabilization of nanoparticles. PMID- 26673352 TI - Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1). AB - BACKGROUND: There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting. PATIENTS AND METHODS: Patients with aUC a creatinine clearance (CrCl) of <60 but >=30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1). They received vinflunine 250 or 280 mg/m(2) (based on baseline CrCl) on day 1, plus either gemcitabine [750 mg/m(2) escalated to 1000 mg/m(2) in cycle 2 if no toxicity grade (G) >=2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days]. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (alpha = 5%, beta = 20%). RESULTS: Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively. CONCLUSION: Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study. CLINICALTRIALS.GOV PROTOCOL IDENTIFIER: NCT 01599013. PMID- 26673355 TI - Can Platelet-Rich Plasma Protect Rat Achilles Tendons From the Deleterious Effects of Triamcinolone Acetonide? AB - BACKGROUND: Triamcinolone acetonide (TA) injections are widely used for tendinitis but have deleterious effects, including tendon degeneration or tendon rupture. PURPOSE: To investigate whether adding platelet-rich plasma (PRP), a blood fraction that participates in tissue repair processes, to TA can prevent its deleterious effects. STUDY DESIGN: Controlled laboratory study. METHODS: Rat Achilles tendons were injected with TA, TA + PRP, PRP alone, or saline (control). Biomechanical testing and histological analyses were performed on Achilles tendons 1 week after injections. RESULTS: The maximum failure loads in the control, TA, TA + PRP, and PRP groups were 31.7 +/- 2.3, 19.0 +/- 3.6, 31.0 +/- 7.1, and 30.2 +/- 6.8 N, respectively. The tendon stiffness in the control, TA, TA + PRP, and PRP groups was 12.1 +/- 1.8, 7.5 +/- 1.8, 11.0 +/- 2.8, and 11.3 +/ 2.5 N/mm, respectively. The maximum failure load and stiffness were significantly lower in the TA group compared with the other 3 groups. There was no significant difference between the TA + PRP and control groups. Cell invasions, vacuolation, collagen attenuation, and increased type III collagen expression were histologically observed in the TA group; however, these changes were prevented by the simultaneous administration of PRP. CONCLUSION: Administering PRP may prevent deleterious effects caused by TA; therefore, PRP may be used as a protective agent in clinical situations. CLINICAL RELEVANCE: PRP can be useful as a protective agent for sports injury patients receiving local corticosteroid injections. PMID- 26673356 TI - Compression of the Popliteal Artery after Posterior Cruciate Ligament Reconstruction Using the Tibial Inlay Technique. AB - Popliteal artery compression rarely occurs after posterior cruciate ligament (PCL) reconstruction using the tibial inlay technique that allows for direct visualization of the surgical field. However, we experienced a popliteal artery compression after PCL reconstruction performed using the technique, which eventually required re-operation. Here, we report this rare case and discuss reasons of popliteal artery compression. PMID- 26673371 TI - Betacellulin in Chronic Periodontitis Patients With and Without Type 2 Diabetes Mellitus: An Immunohistochemical Study. AB - BACKGROUND: The host immune response to bacterial dental plaque determines periodontal disease susceptibility by increasing the secretion of inflammatory cytokines. The Epidermal Growth Factor family cytokines stimulate proliferation and keratinization of cells in dermis and oral epithelium. Epidermal Growth Factor family consists of Amphiregulin, Betacellulin, Epiregulin, Epigen, Heparin binding Epidermal Growth Factor like growth factor and transforming Growth Factor alpha. AIM: The current study aimed to investigate expression of Betacellulin in chronic periodontitis patients with and without type 2 diabetes mellitus and thereby assessing role of betacellulin in periodontal health and disease. MATERIALS AND METHODS: Present study comprised of 90 participants, age ranges from 18 to 60-year-old, for the period of March 2010 to May 2011. Participants were categorized into three groups based Gingival index (GI), probing depth (PD) and clinical attachment loss (CA Loss). Group 1 consisted 30 individuals with clinically healthy periodontium, Group-2 consisted 30 individuals with GI>1, PD>=5 mm, and CA Loss>3 mm. Group-3 (Chronic Periodontitis with type 2 diabetes mellitus) consisted 30 with GI >1, PD>=5 mm, and CA Loss>3 mm. Immunohistochemical localization and quantification of Betacellulin was done in gingival tissue samples from all groups. RESULTS: Data showed expression of Betacellulin were higher in chronic periodontitis as compared to healthy. A positive correlation found in Betacellulin expression and Probing Depth in chronic periodontitis. CONCLUSION: This footmark study impacts the role of Betacellulin in pathogenesis and progression of periodontal disease which will help in exploration of novel immunotherapeutic strategies and immunological research activity in this field. PMID- 26673373 TI - Nursing Ethics: A Lifelong Commitment. AB - Over the past 30 years, the health-care context as well as the roles and responsibilities of nurses have drastically changed. Leaders in nursing around the world recognize that the health-care system is stressed and the well-being of the nursing workforce plagued by the pressures and challenges it faces in everyday practice. We do not intend to make a strong normative argument for why nursing ethics education should be done in a certain way, but instead show from where we have come and to where we can go, so that educators are positioned to address some of the current shortcomings in ethics education. Our goal is to provide an illustration of ethics education as an interwoven, ongoing, and essential aspect of nursing education and professional development. By developing professional identity as character, we hope that professional nurses are given the skills to stand in the face of adversity and to act in a way that upholds the core competencies of nursing. Ultimately, health-care organizations will thrive because of the support they provide nurses and other health-care professionals. PMID- 26673372 TI - Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib. AB - BACKGROUND: Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia. METHODS: Thirty-one patients with advanced (n = 16) or high-risk resected (n = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration. RESULTS: Twelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre treatment sarcopenia was not associated with grades 3-4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p < 0.01) after 3 months of treatment. Grades 1-2 anaemia and grades 1-2 fatigue were more frequent for sarcopenic than non-sarcopenic patients (83% vs. 26%, P < 0.01 and 42% vs. 5%, P = 0.02, respectively). CONCLUSIONS: Sarcopenia is reversible in some GIST patients treated with imatinib. Pre-imatinib sarcopenia is predictive of non severe toxicities, particularly anaemia and fatigue. PMID- 26673374 TI - Shattered, Suffering, and Silenced: Sharon's Story. AB - This chapter presents a case study of a 30-year-old female news reporter in Albuquerque, New Mexico, named Sharon Fullilove. The case is presented as a personal narrative by her mother, who is a critical care nurse, former chief nurse, Level I trauma unit commander, and colonel in the U.S. Air Force. The narrative is followed by excerpts from Sharon's chart that confirm a series of decisions made by both the hospital and the providers. The subsequent narrative is meant to give the reader an opportunity to reflect on the variety of clinical ethics questions that emerge when a patient enters into a contract with a physician and hospital for care. The goal is not to perform a thorough ethical analysis of the case but to let the reader experience what it is like when best practice standards, attention to patient care, and compassionate concern for family members are set aside. The case concludes with a set of broad questions that can be used for further discussion. Hopefully, this case will bring to the forefront the centrality of ethics in professional decision-making within the context of medical care. PMID- 26673375 TI - Family Impact of Military Mental Health Stigma: A Narrative Ethical Analysis. AB - Our past lessons from war trauma have taught us that mental health-care stigma and other issues surrounding mental health-seeking behaviors can negatively impact the healing trajectory and long-term function for service members and their families. It can take years to decades before a service member seeks professional help for psychological distress, if he or she seeks it at all. Unfortunately, signs of personal and family problems can be subtle, and consequences, such as suicide, tragic. In this chapter, we consider the story one military health-care provider submitted in response to a study solicitation that read: Please provide your personal story telling me about any psychological distress you may have experienced after returning from deployment and your personal challenges accessing care and/or remaining in treatment. This story is analyzed to explore the moral implications of his experience for the military and for other service members. The main points to be highlighted are that altruism can leave altruists more vulnerable, military mental health stigma may exacerbate this risk, and military families may profoundly be affected. PMID- 26673376 TI - Ethical Analysis of a Qualitative Researcher's Unease in Encountering a Participant's Existential Ambivalence. AB - Gaining in-depth understanding of the experiences of persons who have suffered traumatic events with physical and psychological sequelae is important for building effective interventions. However, qualitative research of this kind can be emotionally difficult for the researcher whose research interests derive from practice experiences with the population studied. It may be difficult for the researcher to separate the role of inquirer from that of practitioner. We explore this issue using ethical analysis to differentiate the responsibilities of the researcher from those of the clinician. In the first part of the chapter, we provide some background on the population studied and traumatic spinal cord injury and its aftermath as context for the issues raised by the narrative. Then, we describe briefly the first author's research exploring the meaning of bodily changes and embodiment in persons who have suffered a traumatic spinal cord injury. We provide the part of Jack's story that most troubled the researcher and led her to discuss the situation with an ethics colleague. Finally, we use the tools of moral reasoning, ethical analysis, and principles of research ethics to explore the pertinent excerpt of the narrative. The resulting clarifications are laid out for the reader with the intent of assisting other qualitative researchers in determining the extent and limits of their obligations to participants of qualitative studies, especially those that explore sensitive issues. PMID- 26673377 TI - Ethical Issues in Family Care Today. AB - The abstract consideration of ethical questions in family and informal caregiving might rightly be criticized for ignoring the lived experience of people. This chapter seeks to avoid such oversight by reflecting on ethical issues in family care in a way that is based on careful social scientific inquiry into the well being of caregivers. The chapter draws on our research and experience in working with family caregivers, both professionally and personally. We step back from a practical concern with policies to support the well-being of caregivers to consider ethical issues associated with their typically hidden role. The chapter begins by noting the growing reliance on family care today. It proceeds to outline the dynamic experience of moving into and out of the caregiver role, before discussing key ethical issues associated with family care. Many of these stem from the risk that caregivers can come to share in the reduced circumstances and vulnerability of those for whom they care. Critical ethical issues are related to the typically "unboundaried" responsibility of family caregivers for the well-being of the cared-for person, something that can be contrasted with the more boundaried and intermittent responsibility of formal caregivers. Additionally, all too often, family caregivers encounter situations where their responsibilities exceed their capacities, but where a choice to not provide care will result in harm to the cared-for person. In discussing these issues, this chapter seeks to make the case for developing more responsive forms of support that promote positive benefits for both caregivers and care recipients. PMID- 26673378 TI - Self-Neglect: Ethical Considerations. AB - Self-neglect is a significant international public health issue. Estimates suggest that there may be over one million cases per year in the United States. Aging populations will put more people at risk of self-neglect. This chapter presents background literature, self-neglect definitions and policy context, risk factors, and a brief overview of research on perspectives of self-neglect from both clients and community health and social care professionals. A case study is presented from the perspective of an individual and is used to explore ethical issues therein. A person-centered assessment within a multidisciplinary team approach is required for building a therapeutic relationship with clients. Capacity is a central issue in the management of responses to self-neglect. Ethical considerations of importance for community health and social care professionals include beneficence and nonmaleficence, autonomy and capacity, and respect for people's rights and dignity. A model of ethical justification is presented to explain dilemmas, challenges, and actions. Competence of professionals, multidisciplinary team working, informed consent, privacy, confidentiality, and best interest are also critical considerations. Effective decision making by an interdisciplinary team of professionals needs to be person centered and give due consideration to the best interest of self-neglecting clients. The purpose of this chapter is to provide an in-depth discussion and examination of ethical issues and challenges relating to self-neglecting clients. PMID- 26673379 TI - Military Serving at What Cost? The Effects of Parental Service on the Well-Being Our Youngest Military Members. AB - Since the onset of war in Iraq and Afghanistan in April 2002, much attention has been given to the effect of war on servicemen and servicewomen who have now been serving in combat for over thirteen years, the longest sustained war in American history. Many service members have served multiple tours in Iraq and Afghanistan and suffered from the visible and invisible wounds of war. Much work has been done in the Veterans Administration, the Department of Defense, and the civilian sector after observing the effects of multiple deployments and overall military service on the service member. A survey of the literature revealed that the ethics of conducting research on programs to assist these brave men and women is fraught with ethical concerns based on a military culture that often precludes autonomy and privacy. While strides have been made in developing strategies to assist service members deal with their military service issues, a serious lack of information exists on the impact of a parent's service on the health and well being of military children. A discussion of current research on services for children is presented with an analysis of the ethical problems that have precluded adequate study of those who need society's help the most. PMID- 26673380 TI - The Gene Pool: The Ethics of Genetics in Primary Care. AB - AIM: The purpose of this integrative review is to critically analyze the research literature regarding ethical principles that surround the integration of genetics and genomics in primary care clinical practice. BACKGROUND: Advanced practice nurses (APRNs) play an important role in the provision of primary care services, in the areas of obstetrics, pediatrics, family practice, and internal medicine. Advances in genetic and genomic science are infiltrating these day-to-day health care systems and becoming an integral part of health-care delivery. It is imperative for primary care providers to understand the ethical, legal, and social implications of genetics and genomics. METHODS: A comprehensive multistep search of CINAHL, MEDLINE, Academic Search Premier, PsycINFO, Web of Science, and Scopus databases was conducted to identify primary research articles published from 2003 to 2015 that evaluated ethical issues related to genetics and genomics in U. S. primary care practice. A sample of 26 primary research articles met the inclusion criteria. Whittemore and Knafl's (2005) revised framework for integrative reviews was used to guide the analysis and assess the quality of the studies. Key findings from the studies are discussed according to Beauchamp and Childress's (2009) ethical principles of autonomy, beneficence, nonmaleficence, and justice. RESULTS: Research conducted to date is mainly qualitative and descriptive and the analysis revealed several ethical challenges to implementing genetics and genomics in primary care settings. CONCLUSION: The review suggests that there are several implications for research, education, and the development of primary care practice that support APRNs delivering genetic and genomic care while incorporating knowledge of ethical principles. More research needs to be conducted that evaluates the actual genetic/genomic ethical issues encountered by primary care providers. PMID- 26673381 TI - Ethical Considerations Regarding the Use of Smart Home Technologies for Older Adults: An Integrative Review. AB - PROBLEM: With the wide adoption and use of smart home applications, there is a need for examining ethical issues regarding smart home use at the intersection of aging, technology, and home environment. PURPOSE: The purpose of this review is to provide an overview of ethical considerations and the evidence on these ethical issues based on an integrative literature review with regard to the utilization of smart home technologies by older adults and their family members. REVIEW DESIGN AND METHODS: We conducted an integrative literature review of the scientific literature from indexed databases (e. g., MEDLINE, CINAHL, and PsycINFO). The framework guiding this review is derived from previous work on ethical considerations related to telehealth use for older adults and smart homes for palliative care. Key ethical issues of the framework include privacy, informed consent, autonomy, obtrusiveness, equal access, reduction in human touch, and usability. RESULTS: Six hundred and thirty-five candidate articles were identified between the years 1990 and 2014. Sixteen articles were included in the review. Privacy and obtrusiveness issues appear to be the most important factors that can affect smart home technology adoption. In addition, this article recommends that stigmatization and reliability and maintenance of the system are additional factors to consider. IMPLICATIONS: When smart home technology is used appropriately, it has the potential to improve quality of life and maintain safety among older adults, ultimately supporting the desire of older adults for aging in place. The ability to respond to potential ethical concerns will be critical to the future development and application of smart home technologies that aim to enhance safety and independence. PMID- 26673382 TI - No Need to Object: Ethical Obligations for Interprofessional Collaboration in Emergency Department Discharge Planning. AB - Emergency departments (EDs) serve a wide range of patient needs. A crucial aspect of safe and effective care in the ED is to appropriately transition patients to the next level of care. In most EDs, this disposition planning is done exclusively by physicians, which has the potential to result in unacceptable harm. A virtue ethics approach demonstrates the need for explicit inclusion of nurses in disposition planning. In utilizing this approach, it is necessary to examine four focal virtues as they relate to the work of disposition planning and the moral character of the nurse. The virtues of prudence, trustworthiness, vigilance, and courage show that interprofessional collaboration is needed during disposition planning to promote patient safety, facilitate interprofessional relationships, and prevent moral distress. The majority of literature on disposition planning is empirical in nature; this chapter adds a normative argument and a motive for policy reform. PMID- 26673383 TI - Postdeployment Reintegration: The Ethics of Embodied Personal Presence and the Formation of Military Meaning. AB - In 2014, the Institute of Medicine published a meta-analysis on current military reintegration programs, suggesting they have failed to improve postdeployment behavioral health. In this chapter, I explore some of the issues associated with the two paradigm reintegration programs supported by the Department of Defense (DoD), namely, BATTLEMIND postdeployment debriefings and Master Resilience Training. My discussion will be located within a subpopulation of military personnel I call warriors, particularly those men who have been exposed to combat. In performing a normative analysis of current reintegration programs, I rely on an ethics of embodied personal presence as a derivative focus of both nursing ethics and the just war tradition. Using an interdisciplinary approach to evaluate warriors' experiences of training across the military life cycle illustrates how reintegration challenges have been construed as potential pathology because disembodied reintegration programs do not consider the influence of military training and lifestyle in the development of certain health behaviors. When compared to the warrior's lived experience, a broader set of reintegration challenges emerge that cannot be fully captured by the symptoms of posttraumatic stress. Therefore, new reintegration programs need to be developed. Although I do not provide explicit details concerning what these reintegration programs should look at, I suggest that the DoD turn to something akin to the Healthy People campaign. PMID- 26673384 TI - Ethical Issues Encountered by Military Nurses During Wartime. AB - Military nurses encounter similar issues as civilian nurses in daily practice situations; however, wartime and humanitarian missions may bring unique and difficult ethical dilemmas. While nursing has the American Nurses Association code of ethics to provide a framework to guide ethical practice decisions, conflicts may arise from the unique aspects of nursing within a wartime environment. Understanding those conflicts occuring within the military wartime scenario can provide nurses with experiential examples from which to derive strategies for personal coping and professional behavior and decision making. This chapter describes the research that has focused upon the identification of these issues, the effects from uresolved issues, and those directions for future research to better prepare miltiary nurses before and during deployment. PMID- 26673385 TI - The Promise and Potential Perils of Big Data for Advancing Symptom Management Research in Populations at Risk for Health Disparities. AB - Symptom management research is a core area of nursing science and one of the priorities for the National Institute of Nursing Research, which specifically focuses on understanding the biological and behavioral aspects of symptoms such as pain and fatigue, with the goal of developing new knowledge and new strategies for improving patient health and quality of life. The types and volume of data related to the symptom experience, symptom management strategies, and outcomes are increasingly accessible for research. Traditional data streams are now complemented by consumer-generated (i.e., quantified self) and "omic" data streams. Thus, the data available for symptom science can be considered big data. The purposes of this chapter are to (a) briefly summarize the current drivers for the use of big data in research; (b) describe the promise of big data and associated data science methods for advancing symptom management research; (c) explicate the potential perils of big data and data science from the perspective of the ethical principles of autonomy, beneficence, and justice; and (d) illustrate strategies for balancing the promise and the perils of big data through a case study of a community at high risk for health disparities. Big data and associated data science methods offer the promise of multidimensional data sources and new methods to address significant research gaps in symptom management. If nurse scientists wish to apply big data and data science methods to advance symptom management research and promote health equity, they must carefully consider both the promise and perils. PMID- 26673387 TI - Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework. AB - Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements. PMID- 26673389 TI - Gold catalysis in total synthesis - recent achievements. AB - In this critical review the applications of gold catalysed reactions in total synthesis during the years since our last article are reviewed. At the end of this article a literature analysis is conducted to evaluate the progress in this field. PMID- 26673388 TI - The cardiac connexome: Non-canonical functions of connexin43 and their role in cardiac arrhythmias. AB - Connexin43 is the major component of gap junctions, an anatomical structure present in the cardiac intercalated disc that provides a low-resistance pathway for direct cell-to-cell passage of electrical charge. Recent studies have shown that in addition to its well-established function as an integral membrane protein that oligomerizes to form gap junctions, Cx43 plays other roles that are independent of channel (or perhaps even hemi-channel) formation. This article discusses non-canonical functions of Cx43. In particular, we focus on the role of Cx43 as a part of a protein interacting network, a connexome, where molecules classically defined as belonging to the mechanical junctions, the gap junctions and the sodium channel complex, multitask and work together to bring about excitability, electrical and mechanical coupling between cardiac cells. Overall, viewing Cx43 as a multi-functional protein, beyond gap junctions, opens a window to better understand the function of the intercalated disc and the pathological consequences that may result from changes in the abundance or localization of Cx43 in the intercalated disc subdomain. PMID- 26673390 TI - Live-attenuated H7N9 influenza vaccine is weak, yet strong. PMID- 26673392 TI - Identification of novel membrane-associated prostaglandin E synthase-1 (mPGES-1) inhibitors with anti-influenza activities in vitro. AB - Influenza A virus (IAV) is a major public health concern that leads to high morbidity and mortality worldwide. Despite various vaccination programs and development of drugs targeting essential viral proteins, the emergence of drug resistant variants has been frequently reported and the therapeutic options are limited. Because exaggerated inflammation is considered as an important factor in disease pathogenesis, immunomodulatory agents that effectively suppress cytokine responses are needed for the treatment of IAV infection. Membrane-associated prostaglandin E synthase-1 (mPGES-1) is an enzyme responsible for the production of prostaglandin E2 (PGE2) that is the best-characterized immune modulatory lipid in vitro and in vivo models of inflammation. In the present study, we tested the anti-influenza activities of mPGES-1 inhibitors, using a phenotype-based assay involving image analyses. Seven primary hits among 49 compounds targeting mPGES-1 exhibited anti-influenza activities against A/Puerto Rico/8/1934 (H1N1) in a dose dependent manner. The most effective hit, MPO-0047, suppressed influenza-induced p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) activation. We also showed that mRNA levels of TNF-alpha, IL-8, CCL5/RANTES, and CXCL10/IP-10 were significantly reduced by the treatment of influenza-infected cells with MPO-0047. Exogenous PGE2 reversed the inhibitory effects of MPO-0047. Our results showed that this selective mPGES-1 inhibitor has anti-influenza effects by inhibiting PGE2 production, which suppresses the induction of pro inflammatory genes. Taken together our data revealed that mPGES-1 inhibitor has the potential for further development as an influenza therapeutic agent. PMID- 26673391 TI - H7N9 live attenuated influenza vaccine in healthy adults: a randomised, double blind, placebo-controlled, phase 1 trial. AB - BACKGROUND: H7N9 avian influenza viruses characterised by high virulence and presence of mammalian adaptation markers have pandemic potential. Specific influenza vaccines remain the main defence. We assessed the safety and immunogenicity of an H7N9 live attenuated influenza vaccine (LAIV) candidate in healthy adult volunteers. METHODS: We did a phase 1, double-blind, randomised, placebo-controlled trial in Saint Petersburg, Russia. Eligible participants were healthy adults aged 18-49 years. The participants were randomised 3:1 to receive live vaccine or placebo, according to a computer-generated randomisation scheme. Two doses of vaccine or placebo were administered intranasally 28 days apart, each followed by 7 day stays in hospital. Immune responses were assessed in nasal swabs, saliva, and serum specimens collected before and 28 days after each vaccine dose. The primary outcome was the safety profile. This trial is registered with ClinicalTrials.gov, number NCT02480101. FINDINGS: Between Oct 21, 2014, and Oct 31, 2014, 40 adults were randomised, of whom 39 (98%) were included in the per-protocol analysis (29 in the vaccine group and ten in the placebo group). The frequency of adverse events did not differ between the vaccine and placebo groups. Seroconversion of neutralising antibodies was seen in 14 participants after the first vaccine dose (48%, 95% CI 29.4-67.5) and 21 after the second vaccine dose (72%, 52.8-87.3). Immune responses were seen in 27 of 29 recipients (93%, 95% CI 77.2-99.2). Adverse effects were seen in 19 (63%) vaccine recipients and nine (90%) placebo recipients after the first dose and in nine (31%) and four (40%), respectively, after the second dose. These effects were mainly local and all were mild. INTERPRETATION: The H7N9 LAIV was well tolerated and safe and showed good immunogenicity. FUNDING: WHO. PMID- 26673393 TI - Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence. AB - PURPOSE: The aim of this study is to explore whether a methylation diet influences risk for adenomatous polyps (AP) either independently, or interactively with one-carbon metabolism-dependent gene variants, and whether such a diet modifies blood homocysteine, a biochemical phenotype closely related to the phenomenon of methylation. METHODS: 249 subjects were examined using selective fluorescence, PCR and food frequency questionnaire to determine homocysteine, nine methylation-related gene polymorphisms, dietary methionine, 5 methyltetrahydrofolate, vitamins B6 and B12. RESULTS: 1). Both dietary methionine and 5-methyltetrahydrofolate intake are significantly associated with plasma homocysteine. 2). Dietary methionine is related to AP risk in 2R3R-TS wildtype subjects, while dietary B12 is similarly related to this phenotype in individuals heterozygous for C1420T-SHMT, A2756G-MS and 844ins68-CBS, and in those recessive for 2R3R-TS. 3). Dietary methionine has a marginal influence on plasma homocysteine level in C1420T-SHMT heterozygotes, while B6 exhibits the same effect on homocysteine in C776G-TCN2 homozygote recessive subjects. Natural 5 methyltetrahydrofolate intake is interesting: Wildtype A1298C-MTHFR, heterozygote C677T-MTHFR, wildtype A2756G-MS and recessive A66G-MSR individuals all show a significant reciprocal association with homocysteine. 4). Stepwise regression of all genotypes to predict risk for AP indicated A2756G-MS and A66G-MSR to be most relevant (p = 0.0176 and 0.0408 respectively). Results were corrected for age and gender. CONCLUSION: A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR) were directly associated with AP occurrence. PMID- 26673394 TI - Phospholamban spontaneously reconstitutes into giant unilamellar vesicles where it generates a cation selective channel. AB - Phospholamban (PLN) is a small integral membrane protein, which modulates the activity of the Sarcoplasmic Reticulum Ca(2+)-ATPase (SERCA) of cardiac myocytes. PLN, as a monomer, can directly interact and tune SERCA activity, but the physiological function of the pentameric form is not yet fully understood and still debated. In this work, we reconstituted PLN in Giant Unilamellar Vesicles (GUVs), a simple and reliable experimental model system to monitor the activity of proteins in membranes. By Laser Scanning Confocal Microscopy (LSCM) and Fluorescence Correlation Spectroscopy (FCS) we verified a spontaneous reconstitution of PLN into the phospholipid bilayer. In parallel experiments, we measured with the patch clamp technique canonical ion channel fluctuations, which highlight a preference for Cs(+) over K(+) and do not conduct Ca(2+). The results prove that PLN forms, presumably in its pentameric form, a cation selective ion channel. PMID- 26673395 TI - Highly Flexible and Conductive Printed Graphene for Wireless Wearable Communications Applications. AB - In this paper, we report highly conductive, highly flexible, light weight and low cost printed graphene for wireless wearable communications applications. As a proof of concept, printed graphene enabled transmission lines and antennas on paper substrates were designed, fabricated and characterized. To explore its potentials in wearable communications applications, mechanically flexible transmission lines and antennas under various bended cases were experimentally studied. The measurement results demonstrate that the printed graphene can be used for RF signal transmitting, radiating and receiving, which represents some of the essential functionalities of RF signal processing in wireless wearable communications systems. Furthermore, the printed graphene can be processed at low temperature so that it is compatible with heat-sensitive flexible materials like papers and textiles. This work brings a step closer to the prospect to implement graphene enabled low cost and environmentally friendly wireless wearable communications systems in the near future. PMID- 26673396 TI - The Extractive Industries: Can We Find New Solutions to Seemingly Intractable Problems? PMID- 26673397 TI - Opposite Trends in the Regulation of Pornography? Policy Differentiation and Policy Convergence Across 26 Countries Between 1960 and 2010. AB - In recent decades, the regulation of pornography has been confronted with challenges emerging from cultural change, economic interests, and technological progress. As a result, the respective regulatory frameworks have changed substantially in many countries. These changes have been accompanied by fierce political struggles and societal value conflicts. However, there are few comparative studies on the reactions of national governments to these problems. In this article, we present new empirical data on the regulation of pornography in 26 countries between 1960 and 2010. To assess regulatory change, we rely on a new measurement approach that considers the extent to which governments intervene into individual freedoms and the degree to which noncompliance with these rules is actually sanctioned. Our analysis reveals a trend toward more permissive styles of pornography regulation. However, this trend is accompanied by growing regulatory specialization and a convergence toward more interventionist regimes for special types of pornography. PMID- 26673398 TI - Contrast-enhanced ultrasound after endovascular aortic repair-current status and future perspectives. AB - An increasing number of patients with abdominal aortic aneurysms (AAAs) are undergoing endovascular aortic repair (EVAR) instead of open surgery. These patients require lifelong surveillance, and the follow-up imaging modality of choice has been traditionally computed tomography angiography (CTA). Repetitive CTA imaging is associated with cumulative radiation exposure and requires the administration of multiple doses of nephrotoxic contrast agents. Contrast enhanced ultrasound (CEUS) has emerged as an alternative strategy in the follow up of patients with EVAR and demonstrates high sensitivity and specificity for detection of endoleaks. In fact, a series of studies have shown that CEUS is at least performing equal to computed tomography for the detection and classification of endoleaks. This article summarizes current evidence of CEUS after EVAR and demonstrates its usefulness via various patient cases. PMID- 26673399 TI - Correction: A proteomic study of Shengmai injection's mechanism on preventing cardiac ischemia-reperfusion injury via energy metabolism modulation. AB - Correction for 'A proteomic study of Shengmai injection's mechanism on preventing cardiac ischemia-reperfusion injury via energy metabolism modulation' by Shuyu Zhan et al., Mol. BioSyst., 2015, 11, 540-548. PMID- 26673401 TI - Coming of age: pharmacy practice in the 21st century. AB - Individuals, families, health plans and governments are struggling with the growing importance of managing chronic, non-communicable diseases. People in many countries are living longer and thus are facing many years of managing hypertension, diabetes and hyperlipidemia - often complicated by obesity, declining physical activity and changing diets. The financial burden this places on governments, employers, and individuals purchasing health care services is growing and solutions are being sought on how to both finance this care and deliver the best care possible. New ideas are emerging that look to newfound resources, and one untapped resource increasingly being utilized is the clinical pharmacist. After many years being primarily involved in medication supply-chain management, the assistance that highly skilled pharmacists can provide medical providers and their patients is now being recognized. In order to realize fully the benefits of clinical pharmacists, governments, health plans and medical providers are taking a second look at the wisdom of maintaining the long-standing policy of compensating pharmacists only for filling prescriptions. PMID- 26673400 TI - Genetic polymorphisms are associated with hair, blood, and urine mercury levels in the American Dental Association (ADA) study participants. AB - BACKGROUND/AIMS: Mercury (Hg) is a potent toxicant of concern to the general public. Recent studies suggest that several genes that mediate Hg metabolism are polymorphic. We hypothesize that single nucleotide polymorphisms (SNPs) in such genes may underline inter-individual differences in exposure biomarker concentrations. METHODS: Dental professionals were recruited during the American Dental Association (ADA) 2012 Annual Meeting. Samples of hair, blood, and urine were collected for quantifying Hg levels and genotyping (88 SNPs in classes relevant to Hg toxicokinetics including glutathione metabolism, selenoproteins, metallothioneins, and xenobiotic transporters). Questionnaires were administrated to obtain information on demographics and sources of Hg exposure (e.g., fish consumption and use of dental amalgam). Here, we report results for 380 participants with complete genotype and Hg biomarker datasets. ANOVA and linear regressions were used for statistical analysis. RESULTS: Mean (geometric) Hg levels in hair (hHg), blood (bHg), urine (uHg), and the average estimated Hg intake from fish were 0.62ug/g, 3.75ug/L, 1.32ug/L, and 0.12ug/kg body weight/day, respectively. Out of 88 SNPs successfully genotyped, Hg biomarker levels differed by genotype for 25 SNPs, one of which remained significant following Bonferroni correction in ANOVA. When the associations between sources of Hg exposure and SNPs were analyzed with respect to Hg biomarker concentrations, 38 SNPs had significant main effects and/or gene-Hg exposure source interactions. Twenty-five, 23, and four SNPs showed significant main effects and/or interactions for hHg, bHg, and uHg levels, respectively (p<0.05), and six SNPs (in GCLC, MT1M, MT4, ATP7B, and BDNF) remained significant following Bonferroni correction. CONCLUSION: The findings suggest that polymorphisms in environmentally-responsive genes can influence Hg biomarker levels. Hence, consideration of such gene-environment factors may improve the ability to assess the health risks of Hg more precisely. PMID- 26673403 TI - Ethylene glycol-assisted coating of titania on nanoparticles. AB - Coating titania shells onto sub-micron sized particles has been widely studied recently, with success mainly limited to objects with sizes above 50 nm. Direct coating on particles below this size has been difficult to attain especially with good control over properties such as thickness and crystallinity. Here we demonstrate that titanium-glycolate formed by reacting titanium alkoxide and ethylene glycol is an excellent precursor for coating titania on aqueous nanoparticles. The new coating method is particularly useful for its ability to coat materials lacking strong polymers or ligands which are frequently needed to facilitate typical titania coatings. We demonstrate the effectiveness of the process of coating titania on metal nanoparticles ranging from citrate-stabilized gold and silver spheres to gold nanorods and silver nanoplates, and larger particles such as SiO2 microspheres and polymer spheres. Further the thickness of these coatings can be tuned from a few nanometers to ~40 nm through sequential coatings. These coatings can subsequently be crystallized into TiO2 through refluxing in water or by calcination to obtain crystalline shells. This procedure can be very useful for the production of TiO2 coatings with tunable thickness and crystallinity as well as for further study on the effect of TiO2 coatings on nanoparticles. PMID- 26673402 TI - Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. AB - BACKGROUND: Adoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain. METHODS: We prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity. RESULTS: The DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs. CONCLUSIONS: These findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes. PMID- 26673404 TI - Standards of the Polish Ultrasound Society - update. Ultrasound examination of the aorta and arteries of the lower extremities. AB - A Doppler ultrasound examination has an advantage over other vessel imaging methods as it can be carried out by the patient's bedside and allows to make a diagnosis without exposing the patient to the inconveniency of transportation or an X-ray scan. The purpose of testing the lower extremities and the aorta is to objectively confirm a preliminary clinical diagnosis, localize lesions responsible for the symptoms of the disease, determine their severity and nature (e.g., if they are calcifications or soft lesions), and finally evaluate the hemodynamic criteria. In assessment of the aorta attention is paid not only to aortic diameter measurements, but also to the vascular lumen (dissections with the formation of two flow channels, detachments, balloting of atherosclerotic plaques, etc.) and the presence of atherosclerotic plaques with influx into them (PAU - penetrating ulcer in the plaque or lesions surrounding the aorta, such as retroperitoneal fibrosis or mycotic aneurysm). A correct diagnosis of an abdominal aortic aneurysm requires repeated measurements of the abdominal aorta diameter, and in particular its transverse dimension. When assessing the degree of peripheral arterial stenosis on the basis of hemodynamic parameters, degree of morphological stenosis must be taken into consideration. Collateral circulation may reduce the flow through the main vessel, and thus, the achieved systolic velocities are lower and may understate the degree of the assessed stenosis. Calf vessels are difficult to detect, which results both from the thickness of the muscle and the presence of calcifications. This article has been prepared on the basis of Standards of the Polish Ultrasound Society (2011) and updated on the basis of the latest reports from relevant literature. PMID- 26673405 TI - Effect of alpha-Tocopherol on the Microscopic Dynamics of Dimyristoylphosphatidylcholine Membrane. AB - Vitamin E behaves as an antioxidant and is well known for its protective properties of the lipid membrane. The most biologically active form of vitamin E in the human organism is alpha-tocopherol (aToc). Very recently (Marquardt, D.; et al. J. Am. Chem. Soc. 2014, 136, 203-210) it has been shown that aToc resides near the center of dimyristoylphosphatidylcholine (DMPC) bilayer, which is in stark contrast with other PC membranes, where aToc is located near the lipid water interface. Here we report an unusual effect of this exceptional location of aToc on the dynamical behavior of DMPC membrane probed by incoherent elastic and quasielastic neutron scattering. For pure DMPC vesicles, elastic scan data show two step-like drops in the elastic intensity at 288 and 297 K, which correspond to the pre- and main phase transitions, respectively. However, inclusion of aToc into DMPC membrane inhibits the step-like elastic intensity drops, indicating a significant impact of aToc on the phase behavior of the membrane. This observation is supported by our differential scanning calorimetry data, which shows that inclusion of aToc leads to a significant broadening of the main phase transition peak, whereas the peak corresponding to the pretransition disappears. We have performed quasielastic neutron scattering (QENS) measurements on DMPC vesicles with various concentrations of aToc at 280, 293, and 310 K. We have found that aToc affects both the lateral diffusion and the internal motions of the lipid molecules. Below the main phase transition temperature inclusion of aToc accelerates both the lateral and the internal lipid motions. On the other hand, above the main phase transition temperature the addition of aToc restricts only the internal motion, without a significant influence on the lateral motion. Our results support the finding that the location of aToc in DMPC membrane is deep within the bilayer. PMID- 26673406 TI - Single crystal to single crystal [2+2] photoreactions in chloride and sulphate salts of 4-amino-cinnamic acid via solid-solution formation: a structural and kinetic study. AB - A set of molecular salts with general formula [1H]nA.xH2O (1 = 4-amino-cinnamic acid, A(n-) = NO3(-), BF4(-), PF6(-), SO4(2-), x = 0, 1) was prepared and structurally characterized. [1H]Cl and [1H]2SO4.H2O(II) were found to undergo an SCSC stepwise [2+2] photodimerization, which was followed by X-ray diffraction; a kinetic analysis was performed on single crystals of both salts. In the case of [1H]Cl the photoreaction was also studied on polycrystalline materials. PMID- 26673407 TI - Popliteal Artery Thrombosis after Total Knee Replacement: An Unusual Complication. PMID- 26673408 TI - DDA: A Novel Network-Based Scoring Method to Identify Disease-Disease Associations. AB - Categorizing human diseases provides higher efficiency and accuracy for disease diagnosis, prognosis, and treatment. Disease-disease association (DDA) is a precious information that indicates the large-scale structure of complex relationships of diseases. However, the number of known and reliable associations is very small. Therefore, identification of DDAs is a challenging task in systems biology and medicine. Here, we developed a novel network-based scoring algorithm called DDA to identify the relationships between diseases in a large-scale study. Our method is developed based on a random walk prioritization in a protein protein interaction network. This approach considers not only whether two diseases directly share associated genes but also the statistical relationships between two different diseases using known disease-related genes. Predicted associations were validated by known DDAs from a database and literature supports. The method yielded a good performance with an area under the curve of 71% and outperformed other standard association indices. Furthermore, novel DDAs and relationships among diseases from the clusters analysis were reported. This method is efficient to identify disease-disease relationships on an interaction network and can also be generalized to other association studies to further enhance knowledge in medical studies. PMID- 26673409 TI - The pathogenesis of rheumatoid arthritis in radiological studies. Part II: Imaging studies in rheumatoid arthritis. AB - Early diagnosis of rheumatoid arthritis followed by early initiation of treatment, prevent the destruction of joints and progression to disability in the majority of patients. A traditional X-ray fails to capture early inflammatory changes, while late changes (e.g. erosions) appear after a significant delay, once 20-30% of bone mass has been lost. Sonography and magnetic resonance imaging studies have shown that erosions are seen in the first 3 months from the appearance of symptoms in 10-26% of patients, while in 75% they are seen in the first 2 years of the disease. Power Doppler ultrasound and dynamic magnetic resonance studies allow for qualitative, semiquantitative and quantitative monitoring of the vascularization of the synovium. In addition, magnetic resonance enables assessment of the bone marrow. The ultrasonographic examination using a state-of-the-art apparatus with a high-frequency probe allows for images with great spatial resolution and for the visualization of soft tissues and bone surfaces. However, the changes seen in ultrasonography (synovial pathologies, the presence of exudate, tendons changes, cartilage and bone lesions, pathologies of tendon attachments and ligaments - enthesopathies) are not only specific for rheumatoid arthritis and occur in other rheumatic diseases. Qualitative methods are sufficient for diagnosing the disease through ultrasound or magnetic resonance imaging. Whereas semiquantitative and quantitative scales serve to monitor the disease course - efficacy of conservative treatment and qualification for radioisotope synovectomy or surgical synovectomy - and to assess treatment efficacy. PMID- 26673411 TI - Role of co-regulators in metabolic and transcriptional actions of thyroid hormone. AB - Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri iodothyronine (T3)-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T3 binding leads to dismissal of co repressors and recruitment of co-activators to activate transcription. Co repressors and co-activators were proposed to play opposite roles in the regulation of negative T3 target genes and hypothalamic-pituitary-thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T3, local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co regulators that may emerge from the genome-wide TR recruitment analysis. PMID- 26673410 TI - Development and validation of an immunohistochemistry assay to assess glucocorticoid receptor expression for clinical trials of mifepristone in breast cancer. AB - BACKGROUND: Glucocorticoid receptor (GR) activity has been associated with chemotherapy resistance and poor outcomes in patients with triple negative breast cancer (TNBC). The aim of this study was to develop an immunohistochemistry (IHC) assay to assess GR expression in archival formalin-fixed, paraffin-embedded human invasive breast carcinoma samples. METHODS: An optimized GR assay protocol was developed using rabbit monoclonal antibody to GR clone D8H2. Precision and reproducibility of the GR IHC assay was determined by conducting multiple staining runs of four invasive breast carcinoma samples using replicate serial sections. Assay sensitivity was examined in 50 TNBC samples (>10 mm) obtained from a tumor bank, and 43 paired TNBC samples from a tissue microarray (TMA) (1.5 mm). GR positivity was assessed using a percent scoring approach with a >=10% cutoff for nuclear staining of tumor cells at any intensity. Analysis of the paired TMA cores was performed by averaging the scores of the two cores for each case. RESULTS: Equivalent cellular patterns of GR reactivity were observed in all replicates from the multiple staining runs; coefficients of variation did not exceed 4.7% for average H-scores greater than 3.4, thus meeting the criteria for assay precision and reproducibility (coefficient of variation <=20%). GR expression in TNBC single-tissue samples and TMA cores was characterized as mostly nuclear, with some concurrent cytoplasmic reactivity. Eighty-four percent of the 49 evaluable TNBC samples and 60% of the 42 evaluable paired TMA samples were positive for GR expression. CONCLUSION: A robust and reproducible GR IHC assay was successfully developed for use in invasive breast carcinoma tissues. Differences in GR expression between larger single tissues and smaller TMA cores illustrate the heterogeneity of the disease, as well as potential intra-tumoral heterogeneity. This assay is currently being utilized in clinical trials of mifepristone, a GR antagonist, in patients with TNBC. PMID- 26673412 TI - Help the climate, change your diet: A cross-sectional study on how to involve consumers in a transition to a low-carbon society. AB - This paper explores how the transition to a low-carbon society to mitigate climate change can be better supported by a diet change. As climate mitigation is not the focal goal of consumers who are buying or consuming food, the study highlighted the role of motivational and cognitive background factors, including possible spillover effects. Consumer samples in the Netherlands (n = 527) and the United States (n = 556) were asked to evaluate food-related and energy-related mitigation options in a design that included three food-related options with very different mitigation potentials (i.e. eating less meat, buying local and seasonal food, and buying organic food). They rated each option's effectiveness and their willingness to adopt it. The outstanding effectiveness of the less meat option (as established by climate experts) was recognized by merely 12% of the Dutch and 6% of the American sample. Many more participants gave fairly positive effectiveness ratings and this was correlated with belief in human causation of climate change, personal importance of climate change, and being a moderate meat eater. Willingness to adopt the less meat option increased with its perceived effectiveness and, controlling for that, it was significantly related to various motivationally relevant factors. The local food option appealed to consumer segments with overlapping but partly different motivational orientations. It was concluded that a transition to a low carbon society can significantly benefit from a special focus on the food-related options to involve more consumers and to improve mitigation. PMID- 26673413 TI - Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis. AB - BACKGROUND: Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis. However, RNA-seq carries a few limitations, e.g., the requirement of a significant amount of input RNA and complications led by non-specific mapping of short reads. The Ion AmpliSeq Transcriptome Human Gene Expression Kit (AmpliSeq) was recently introduced by Life Technologies as a whole-transcriptome, targeted gene quantification kit to overcome these limitations of RNA-seq. To assess the performance of this new methodology, we performed a comprehensive comparison of AmpliSeq with RNA-seq using two well-established next-generation sequencing platforms (Illumina HiSeq and Ion Torrent Proton). We analyzed standard reference RNA samples and RNA samples obtained from human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). RESULTS: Using published data from two standard RNA reference samples, we observed a strong concordance of log2 fold change for all genes when comparing AmpliSeq to Illumina HiSeq (Pearson's r = 0.92) and Ion Torrent Proton (Pearson's r = 0.92). We used ROC, Matthew's correlation coefficient and RMSD to determine the overall performance characteristics. All three statistical methods demonstrate AmpliSeq as a highly accurate method for differential gene expression analysis. Additionally, for genes with high abundance, AmpliSeq outperforms the two RNA-seq methods. When analyzing four closely related hiPSC-CM lines, we show that both AmpliSeq and RNA seq capture similar global gene expression patterns consistent with known sources of variations. CONCLUSIONS: Our study indicates that AmpliSeq excels in the limiting areas of RNA-seq for gene expression quantification analysis. Thus, AmpliSeq stands as a very sensitive and cost-effective approach for very large scale gene expression analysis and mRNA marker screening with high accuracy. PMID- 26673414 TI - Ascending aortic dissection diagnosed with the use of point-of-care sonography. Case report. AB - The presented case of a patient in cardiogenic shock in the course of aortic dissection with concomitant cerebral circulation illustrates the effectiveness of sonography in the intensive care unit as a tool that aids the diagnostic process. Point-of-care sonography involves ultrasound assessment performed by the attending physician, being an integral part of a physical examination. A 67-year old female was brought to the emergency department with a suspicion of stroke, comatose, with focal neurological deficits and was admitted to the intensive care unit due to circulatory and respiratory failure. Based on the findings from a bedside ultrasound examination, the diagnostic process was extended, and the patient was rapidly transferred to the department of cardiac surgery with diagnosed ascending aortic dissection. The case presented demonstrates how point of-care sonography facilitates and accerelates the diagnostic process and speeds up the implementation of de finitive treatment thus affecting the patient's outcome. PMID- 26673415 TI - High-frequency ultrasound in carpal tunnel syndrome: assessment of patient eligibility for surgical treatment. AB - Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and a frequent cause of sick leaves because of work-related hand overload. That is why an early diagnosis and adequate treatment (conservative or surgical) are essential for optimal patient management. AIM: The aim of the study is to assess the usefulness of high-frequency ultrasound in CTS for the assessment of patient eligibility for surgical treatment. MATERIAL AND METHODS: The study involved 62 patients (50 women and 12 men, aged 28-70, mean age 55.2) with scheduled surgeries of CTS on the basis of clinical symptoms, physical examination performed by a neurosurgeon and a positive result of EMG testing. The ultrasound examinations of the wrist were performed in all these patients. On the basis of the collected data, the author has performed multiple analyses to confirm the usefulness of ultrasound imaging in assessing patient eligibility for surgical treatment of CTS. RESULTS: US examinations showed evidence of median nerve compression at the level of the carpal tunnel in all of the examined patients. This was further confirmed during surgical procedures. The mean value of the cross-sectional area at the proximal part of the pisiform bone was 17.45 mm(2) (min. 12 mm(2), max. 31 mm(2)). Nerve hypoechogenicity proximal to the nerve compression site was visible in all 62 patients (100%). Increased nerve vascularity on the transverse section was present in 50 patients (80.65%). CONCLUSIONS: Ultrasonography with the use of high-frequency transducers is a valuable diagnostic tool both for assessing patient eligibility for surgical treatment of CTS, and in postoperative assessment of the treatment efficacy. PMID- 26673416 TI - Effect of the molecular targeted drug, erlotinib, against endometrial cancer expressing high levels of epidermal growth factor receptor. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, has been clinically applied for the treatment of a variety of tumors with EGFR overexpression. A phase II clinical study of erlotinib (NCIC IND-148) for recurrent or metastatic endometrial carcinoma (EC) resulted in an unfavorable result. However, in that study, the expression levels of EGFR were not accurately analyzed. Thus, the aim of this study was to re-examine the efficacy of erlotinib in EC cells by utilizing in vitro and in vivo models. METHODS: Tissue samples obtained from patients histologically diagnosed with EC of the uterine corpus were subjected to immunohistochemistry and RT-PCR to determine the protein and mRNA expression levels of EGFR. Western blot and WST-1 assays of EGFR siRNA-transfected HEC-1A, KLE, and Ishikawa cells were used to evaluate the efficacy of erlotinib in tumor cell lines expressing different EGFR levels. Furthermore, HEC-1A and Ishikawa cells were implanted into athymic mice treated with either erlotinib or trastuzumab. RESULTS: At our institution, 20.9% of endometrial cancer patients with low grade endometrioid histology have been diagnosed as stage III and IV. Immunohistochemical analysis and RT-PCR revealed the presence of significant EGFR and EGFR mRNA expression in low-grade endometrioid carcinoma in comparison with high-grade endometrioid carcinoma. In vitro study, WST-1 assay and Western blot analysis revealed that EGFR expression levels were correlated with tumor cell viability. Erlotinib reduced the proliferation of HEC-1A expressing high levels of EGFR, while trastuzumab showed similar effect in Ishikawa cells dominantly expressing human epidermal growth factor receptor type2 (HER2). In vivo erlotinib decreased tumor growth in mice xenografted with HEC-1A cells, whereas this tumor-growth inhibition was not observed in trastuzumab-treated mice xenografted with Ishikawa cell. CONCLUSIONS: EGF contributed to tumor proliferation in EC cell lines along with EGFR expression in vitro. Erlotinib also demonstrated anti-tumor effects in xenograft mice models. Our results suggest that erlotinib continues to have clinical usefulness in specific cases, after taking into consideration the EGFR expression levels. PMID- 26673417 TI - Two different motor learning mechanisms contribute to learning reaching movements in a rotated visual environment. AB - Practice of movement in virtual-reality and other artificially altered environments has been proposed as a method for rehabilitation following neurological injury and for training new skills in healthy humans. For such training to be useful, there must be transfer of learning from the artificial environment to the performance of desired skills in the natural environment. Therefore an important assumption of such methods is that practice in the altered environment engages the same learning and plasticity mechanisms that are required for skill performance in the natural environment. We test the hypothesis that transfer of learning may fail because the learning and plasticity mechanism that adapts to the altered environment is different from the learning mechanism required for improvement of motor skill. In this paper, we propose that a model that separates skill learning and environmental adaptation is necessary to explain the learning and aftereffects that are observed in virtual reality experiments. In particular, we studied the condition where practice in the altered environment should lead to correct skill performance in the original environment. Our 2-mechanism model predicts that aftereffects will still be observed when returning to the original environment, indicating a lack of skill transfer from the artificial environment to the original environment. To illustrate the model prediction, we tested 10 healthy participants on the interaction between a simple overlearned motor skill (straight hand movements to targets in different directions) and an artificially altered visuomotor environment (rotation of visual feedback of the results of movement). As predicted by the models, participants show adaptation to the altered environment and after-effects on return to the baseline environment even when practice in the altered environment should have led to correct skill performance. The presence of aftereffect under all conditions that involved changes in environment demonstrates separation of environmental adaptation and skill learning. Our results support the existence of two distinct learning modules with different adaptation properties. Therefore we suggest that adaptation to an altered environment may not be useful for training new skills. PMID- 26673418 TI - Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR. AB - High-throughput CRISPR screens have shown great promise in functional genomics. We present MAGeCK-VISPR, a comprehensive quality control (QC), analysis, and visualization workflow for CRISPR screens. MAGeCK-VISPR defines a set of QC measures to assess the quality of an experiment, and includes a maximum likelihood algorithm to call essential genes simultaneously under multiple conditions. The algorithm uses a generalized linear model to deconvolute different effects, and employs expectation-maximization to iteratively estimate sgRNA knockout efficiency and gene essentiality. MAGeCK-VISPR also includes VISPR, a framework for the interactive visualization and exploration of QC and analysis results. MAGeCK-VISPR is freely available at http://bitbucket.org/liulab/mageck-vispr . PMID- 26673419 TI - Evaluation of Two PCR Tests for Coxiella burnetii Detection in Dairy Cattle Farms Using Latent Class Analysis. AB - Different tests performed on bulk tank milk samples (BTM) are available to determine the C. burnetii status of herds. However, these tests, which are based on the detection of either antibodies directed against C. burnetii (ELISA) or bacterial DNA (PCR), have limitations. A currently disease-free herd infected in the past may continue to test positive with ELISA due to the persistence of antibodies in animals that were infected and that subsequently cleared the infection. Infectious herds can also be misclassified using PCR because of the absence of bacteria in the BTM when the test is performed. Recently, PCR has been used for bacterial DNA detection in the farm environment, which constitutes the main reservoir of C. burnetii. The objectives of this study were to assess and compare the sensitivities and specificities of one commonly used PCR test in BTM (PCR BTM) and of a PCR applied to environmental samples (PCR DUST) in dairy cattle farms. BTM and dust samples were collected (using environmental swabs) in 95 herds. The evaluation of the performance of the 2 tests was conducted using latent class models accounting for within herd disease dynamics. Parameter estimation was carried out using MCMC, within a Bayesian framework. Two types of priors were used for the specificity of PCR DUST. A model with a uniform prior on 0-1 fitted the data better than a model with a uniform prior on 0.95-1. With the best model PCR DUST had a lower sensitivity than PCR BTM (0.75 versus 0.83) and a specificity of 0.72. The moderately low value for the specificity of PCR DUST suggests that the presence of bacteria on farm is not always associated with persistent infections and shedding of bacteria in milk. PMID- 26673422 TI - Purpura Fulminans Secondary to Rickettsial Infection: A Case Report. AB - Purpura fulminans is an acute life threatening disorder characterized by cutaneous haemorrhagic manifestations and necrosis caused by disseminated intravascular coagulation and dermal vascular thrombosis. In this case a 60-year old male presented with purpuric lesions over both upper and lower limbs and consumption coagulopathy following rickettsial infection. It was diagnosed as purpura fulminans secondary to rickettsial infection with disseminated intravascular coagulation and treated with replacement of platelets and coagulation factors along with antibiotics and doxycycline. PMID- 26673420 TI - A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice. AB - Group B Streptococcus (GBS), a commensal organism, can turn into a life threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4 degrees C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. PMID- 26673421 TI - MicroRNA-181a/b-1 Is Not Required for Innate gammadelta NKT Effector Cell Development. AB - Thymic development of alphabeta T lymphocytes into invariant natural killer (NK) T cells depends on their selection via agonistic lipid antigen presented by CD1d. If successful, newly selected NKT cells gain effector functions already in the thymus. Some gammadelta T cell subsets also acquire effector functions in the thymus. However, it is not clear whether agonistic TCR stimulation is involved in thymic gammadelta T cell selection and development. Here we combine two genetic models to address this question. MiR-181a/b-1-/-mice, which show impaired agonistic T cell selection of invariant alphabeta NKT cells, were crossed to Tcrd H2BeGFP reporter mice to monitor selection, intra-thymic expansion and differentiation of gammadelta T cells. We found that miR-181a/b-1-deficiency had no effect on numbers of thymic gammadelta T cell or on their differentiation towards an IL-17- or IFN-gamma-producing effector phenotype. Also, the composition of peripheral lymph node gammadelta T cells was not affected by miR 181a/b-1-deficiency. Dendritic epidermal gammadelta T cells were normally present in knock-out animals. However, we observed elevated frequencies and numbers of gammadelta NKT cells in the liver, possibly because gammadelta NKT cells can expand and replace missing alphabeta NKT cells in peripheral niches. In summary, we investigated the role of miR-181a/b-1 for selection, intrathymic development and homeostasis of gammadelta T cells. We conclude that miR-181a/b-1-dependent modulation of T cell selection is not critically required for innate development of gammadelta NKT cells or of any other gammadelta T cell subtypes. PMID- 26673423 TI - Diffuse Bacterial Meningitis and Myelitis Secondary to a Diplococcus Organism. PMID- 26673424 TI - DNA-based influenza vaccines as immunoprophylactic agents toward universality. AB - Influenza is an illness of global public health concern. Influenza viruses have been responsible for several pandemics affecting humans. Current influenza vaccines have proved satisfactory safety; however, they have limitations and do not provide protection against unexpected emerging influenza virus strains. Therefore, there is an urgent need for alternative approaches to conventional influenza vaccines. The development of universal influenza vaccines will help alleviate the severity of influenza pandemics. Influenza DNA vaccines have been the subject of many studies over the past decades due to their ability to induce broad-based protective immune responses in various animal models. The present review highlights the recent advances in influenza DNA vaccine research and its potential as an affordable universal influenza vaccine. PMID- 26673425 TI - Self-immunity microcapsules for corrosion protection of steel bar in reinforced concrete. AB - A novel microcapsule-based self-immunity system for reinforced concrete is proposed. Its feasibility for hindering the corrosion of steel rebar by means of lifting the threshold value of [Cl(-)]/[OH(-)] is discussed. Precisely controlled release behavior enables corrosion protection in the case of depassivation. The release process is characterized over a designated range of pH values, and its release characteristics of the microcapsules, triggered by decreasing pH value, are captured by observing that the core crystals are released when exposed to a signal (stimulus). The aim of corrosion protection of steel bar is achieved through the constantly-stabilized passive film, and its stability is promoted using continuous calcium hydroxide released from the microcapsule, restoring alkaline conditions. The test results exhibited that the release process of the microcapsules is a function of time. Moreover, the release rate of core materials could interact with environmental pH value, in which the release rate is found to increase remarkably with decreasing pH value, but is inhibited by high pH levels. PMID- 26673426 TI - Correction: Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine-A Randomized Trial. PMID- 26673427 TI - Severe Pelvic Obliquity Affects Femoral Offset in Patients with Total Hip Arthroplasty but Not Leg-Length Inequality. AB - Leg-length inequality is an extensively studied complication of total hip arthroplasty in normal patients. However, few studies have focused on the pelvic obliquity of coronal pelvic malrotation. We hypothesized that pelvic obliquity with a fixed abduction/adduction contracture deformity of the hip may intraoperatively affect the release of soft tissues, ultimately resulting in a leg-length inequality. This study also investigated whether the femoral and vertical offsets of total hip arthroplasty were correlated with pelvic obliquity. This prospective study divided 98 patients into six groups based on the inclination of pelvic obliquity before total hip arthroplasty. Leg-length inequality, variation of pelvic obliquity, offset, and vertical offset were measured after total hip arthroplasty. Leg-length inequality and vertical offset were not significantly different among groups, whereas the variation of pelvic obliquity was significantly higher in type IIC pelvic obliquity than in other groups. Type IC pelvic obliquity had a significantly shorter offset than did the other groups, which may have been an important factor leading to type IC pelvic obliquity. Pelvic obliquity exhibited no significant effect on leg-length inequality in patients with total hip arthroplasty. A shorter offset may be caused by the higher tension of the abductor in the operated hip, which may result in the formation of type IC pelvic obliquity. Releasing the abductor contracture and restoring femoral offset are important for increasing hip stability and maintaining pelvic balance following total hip arthroplasty. PMID- 26673428 TI - Errors and mistakes in the ultrasound diagnostics of the liver, gallbladder and bile ducts. AB - Ultrasonography is the most widespread imaging technique used in the diagnostics of the pathologies concerning the organs in the abdominal cavity. Similarly to other diagnostic tools, errors may occur in ultrasound examinations. They generally result from inappropriate techniques, which do not conform to current standards, or erroneous interpretation of obtained images. A significant portion of mistakes is caused by inappropriate quality of the apparatus, the presence of sonographic imaging artifacts, unfavorable anatomic variants or improper preparation of the patient for the examination. This article focuses on the examiner-related errors. They concern the evaluation of the liver size, echostructure and arterial and venous vascularization as well as inappropriate interpretation of the liver anatomic variants and the vascular and ductal structures localized inside of it. Furthermore, the article presents typical mistakes made during the diagnosis of the most common gallbladder and bile duct diseases. It also includes helpful data concerning differential diagnostics of the described pathologies of the liver, gallbladder and bile ducts. The article indicates the most frequent sources of mistakes as well as false negative and false positive examples which result from these errors. What is more, the norms used in the liver, gallbladder and bile duct evaluations are presented as well as some helpful guidelines referring to the exam techniques and image interpretation, which allows for reducing the error-making risk. The article has been prepared on the basis of the report published in 2005 by the Polish experts in the field of ultrasonography and extended with the latest findings obtained from the pertinent literature. PMID- 26673429 TI - Risky sexual networks and concentrated HIV epidemics among men who have sex with men in Wenzhou, China: a respondent-driven sampling study. AB - BACKGROUND: The high and continually increasing prevalence of human immunodeficiency virus (HIV) and other sexually transmitted diseases among men who have sex with men (MSM) in China underscores the critical importance of examining the exact sexual networks that result in HIV transmission, as well as HIV infection, using powerful sampling methods, such as respondent-driven sampling (RDS), to improve the sexual health of this population. METHODS: Using RDS, a cross-sectional study was conducted among MSM in Wenzhou, Zhejiang province, China from December 2013 to June 2014. The type of sex, numbers of anal sex partners, male oral sex partners and vaginal sex partners, condom use during each type of sex over the previous 6 months, prevention behaviors, risk perception, and the burdens of HIV and syphilis were investigated and analyzed. RESULTS: Of 424 MSM, a great number of them did anal sex, male oral sex, and vaginal sex during the previous 6 months, and weighted estimates for the prevalence that MSM did not conduct these sexual behaviors were 11.2 % (95 % confidence interval [CI] =6.7-16.50 %), 20.3 % (95 % CI = 15.2-27.1 %), and 58.9 % (95 % CI = 52.1-65.8 %), respectively. Multiple sexual partners, engaging in regular, casual and commercial sex, and lack of condom use during all types of sex were common among MSM. The estimated HIV and syphilis prevalences were 22.8 % (95 % CI = 16.9-28.5 %) and 9.7 % (95 % CI = 6.4-13.6 %), respectively. Of the participants, 53.5 % (95 % CI = 45.3-60.2 %) received HIV-related interventions during the previous year, 48.1 % (95 % CI = 39.7-55.1 %) had never been tested for HIV, and only 14.1 % (95 % CI =10.1-19.2 %) perceived a risk of contracting HIV. Multiple logistic regression analysis revealed that age over 44 years (adjusted odds ratio [AOR] = 3.60, 95 % CI = 1.34-9.64), a monthly income of 3001 4000 yuan (approximately 470-630 US$) (AOR = 1.96, 95 % CI = 1.67-3.60), multiple anal sex partners (AOR = 1.93, 95 % CI = 1.15-3.24), awareness of the possibility of contracting HIV (AOR = 3.18, 95 % CI = 1.56-6.48), and current syphilis infection (AOR = 3.01, 95 % CI = 1.44-6.29) were predictors of HIV infection. CONCLUSIONS: HIV transmission has become highly prevalent and will likely become more prevalent among MSM and their female partners if these risky sexual networks persist. Our findings call for urgent and effective interventions to prevent the rapid transmission of HIV among MSM in Wenzhou. PMID- 26673430 TI - [R-ALERGO. Allergy-healthy routes in Valencia]. AB - R-ALERGO is a project developed by researchers from the Universitat Politecnica de Valencia and the Hospital Universitario La Fe (Valencia, Spain). The main objective of the project is to create a mobile application identifying, within the city of Valencia, the most favorable routes for allergic individuals. The application is developed using nine environmental variables with a potential effect on the development of clinical manifestations in allergic individuals. The application combines the use of spatial analysis based on network technology and implemented with a geographic information system software. The first 01 version is under evaluation for a Healthy app hallmark. The next step in this project is to design a clinical validation process to test its usefulness in allergic individuals. PMID- 26673431 TI - Versatility of the O-Z Flap in the Reconstruction of Facial Defects. AB - BACKGROUND: The O-Z flap has traditionally been used for surgical defects adjacent to critical anatomic structures requiring a repair option that minimizes distortion and functional impairment. However, another advantage of the O-Z flap is that it is tissue conservative, particularly in comparison to primary closure. In fact, the design simply takes the Burow's triangles that would be discarded and rotates them inward. OBJECTIVE: The purpose of this work is to detail the type of post-Mohs defects, which might benefit from consideration of the O-Z flap with emphasis on tissue conservation and restoration of contour to the surgical site. Furthermore, the authors wish to describe unique considerations in each location and methods to appropriately plan the O-Z flap in each circumstance. METHODS AND MATERIALS: The authors reviewed all flaps classified as O-Z in their tumor registry. The approximate size of the defect reconstructed, complications, and long-term outcomes were recorded. RESULTS: O-Z flap implementation is described in detail for repair of defects located at the lateral nasal tip, nose cheek junction, medial canthus, and mid-cheek. CONCLUSION: The O-Z flap can be effectively used to repair defects located at the lateral nasal tip, nose-cheek junction, medial canthus, and mid-cheek. It is a mechanically simple flap with predictable tension vectors, which can be specifically oriented to protect the free margin. PMID- 26673432 TI - Comparison of 532 nm Potassium Titanyl Phosphate Laser and 595 nm Pulsed Dye Laser in the Treatment of Erythematous Surgical Scars: A Randomized, Controlled, Open-Label Study. AB - BACKGROUND: The pulsed dye laser (PDL) has long been used for treatment of erythematous and hypertrophic scars. Its effectiveness has been attributed in large part to its vascular-specificity. The vascular-specific potassium titanyl phosphate (KTP) laser has also been reported to be clinically effective for scars, but has not been compared to the PDL. OBJECTIVE: To compare the safety and clinical efficacy of a 532-nm KTP laser versus a 595-nm PDL in improving the appearance of erythematous surgical scars. METHODS: Twenty patients with matched bilateral erythematous surgical scars or a single linear erythematous scar measuring longer than 5 cm were enrolled in the study. Single scars were divided into equal halves with each half randomized to receive 3 successive treatments at 6-week intervals with either a 532-nm KTP laser (Excel V; Brisbane, CA) or a 595 nm PDL (Cynergy; Cynosure Inc., Chelmsford, MA) at equivalent laser parameters. Bilateral matched scars were similarly randomized to receive three 532-nm KTP or 595-nm PDL treatments. Clinical efficacy was evaluated 12 weeks after the third (final) laser treatment by independent, blinded photographic scar assessments. Secondary evaluations included final investigator and subject treatment/satisfaction assessments, Vancouver scar scale (VSS) scores, subject scar symptoms, intraoperative pain scores, and incidence of side effects. RESULTS: Clinical improvement of erythematous surgical scars was observed with both 532-nm KTP and 595-nm PDL systems. No statistically significant differences between the 2 treatment arms were noted in the independent, blinded photographic scar assessments, investigator and subject treatment/satisfaction assessments, subject scar symptoms, and intraoperative pain scores. The KTP arm produced statistically significant improvement for the vascularity component of the VSS only. Side effects were limited to mild treatment discomfort and minimal transient post-treatment erythema and purpura. No vesiculation, infection, scarring or other adverse events were experienced. Subject satisfaction surveys mirrored the observed clinical effects. CONCLUSION: The-532 nm KTP laser is comparable in efficacy and safety to the 595-nm PDL laser in the treatment of erythematous surgical scars. PMID- 26673433 TI - REFINE-1, a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial With ATX-101, an Injectable Drug for Submental Fat Reduction. AB - BACKGROUND: ATX-101, an injectable form of deoxycholic acid, is approved in the United States and Canada for submental fat (SMF) reduction. OBJECTIVE: To report results of REFINE-1, a randomized, double-blind, placebo-controlled, Phase 3 trial investigating the efficacy and safety of ATX-101. METHODS: Subjects dissatisfied with their moderate or severe SMF received ATX-101 (2 mg/cm) or placebo. Coprimary outcome measures were composite >=1-grade and >=2-grade improvements in clinician-assessed and subject-assessed SMF severity using validated scales at 12 weeks after last treatment. Magnetic resonance imaging (MRI) provided an objective measure of submental volume reduction. Patient reported outcomes were assessed. RESULTS: Among 256 ATX-101-treated and 250 placebo-treated subjects, a >=1-grade composite response was achieved in 70.0% and 18.6%, and a >=2-grade composite response in 13.4% and 0%, respectively (p < .001 for both). The proportion of MRI responders was more than 8 times higher with ATX-101 than placebo (46.3% vs 5.3%; p < .001). ATX-101-treated subjects reported improvement in the psychological impact of SMF and satisfaction with treatment (p < .001 for all assessments vs placebo). Of note, 55% and 75% of ATX 101-treated subjects reported 1-grade improvement in clinician-assessed SMF after 2 and 4 treatments, respectively. Adverse events (primarily localized to the injection site) were mostly mild or moderate, and transient. Marginal mandibular nerve paresis reported in 4.3% of ATX-101-treated subjects (1.0% of all ATX-101 treatment sessions) was mostly mild, transient, and resolved without sequelae. CONCLUSION: ATX-101 is a safe and efficacious, first-in-class, injectable drug for SMF reduction. PMID- 26673434 TI - Commentary on the Sharpness of Blades Used in Dermatologic Surgery. PMID- 26673435 TI - Treatment of 63 Subjects With Digital Mucous Cysts With Percutaneous Sclerotherapy Using Polidocanol. AB - BACKGROUND: Digital mucous cysts (digital myxoid cysts or DMCs) are benign cystic swellings typically affecting the digital distal interphalangeal joint or the proximal nail fold. Many treatment modalities exist; however, permanent scarring, wound infection, and recurrence are common. Polidocanol sclerotherapy has been reported as a potential treatment. OBJECTIVE: To assess the efficacy and safety of percutaneous polidocanol sclerotherapy in the treatment of DMC. MATERIALS AND METHODS: The authors performed polidocanol sclerotherapy in 63 patients (23 men and 40 women). For each patient, the DMC contents were extruded and 3% polidocanol (0.02-0.5 mL) was injected to gently refill the cyst to its previous size. Subjects were reviewed after 6 weeks and offered a second treatment if necessary, and reviewed again after 12 weeks. Changes in lesions and adverse reactions were noted. RESULTS: Of the 63 subjects treated, 43 (68.3%) experienced complete resolution of the cyst by 6 weeks, and 49 (77.8%) experienced complete resolution by 12 weeks. Side effects were minor and had resolved in all patients by 12-week review. CONCLUSION: Percutaneous polidocanol sclerotherapy is a simple, safe, and effective approach to treating DMC, and is suitable for office based practice. PMID- 26673436 TI - Correction: The Association between Meditation Practice and Job Performance: A Cross-Sectional Study. PMID- 26673437 TI - Exercise Increases Cystathionine-gamma-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats. AB - Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-gamma-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)alpha and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERalpha while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling. PMID- 26673438 TI - Norwood Procedure Performed on a Patient With Trisomy 13. AB - Trisomy 13 is associated with a variety of congenital anomalies, some of which are life-threatening and related to poor prognosis. Therefore, cardiac surgery is rarely offered to these patients, especially to those with complex cardiac anomalies. We report the case of a neonate weighing 2324 g who was born with severe congenital heart defects. Transthoracic echocardiography revealed the diagnoses of asplenia, single ventricle, aortic stenosis, coarctation of the aorta, hypoplastic aortic arch, and total anomalous pulmonary venous return. She was hemodynamically unstable. Palliative Norwood procedure with right ventricle pulmonary artery conduit (RV-PA conduit) was performed at the age of 1 day to save her life. On postoperative day 7, chromosome analysis revealed trisomy 13. Echocardiography revealed good heart function; stable hemodynamic status was achieved with minimal amounts of inotropic agents. However, she developed anuria, which did not improve despite situational possible interventions, including peritoneal dialysis and continuous hemodiafiltration. On postoperative day 37, she succumbed to sudden cardiorespiratory failure. Nevertheless, this case indicates that a neonate with trisomy 13 can have a better chance at survival with cardiac surgery such as the Norwood procedure with an RV-PA conduit. PMID- 26673439 TI - Incidence, Predictors and Impact of Severe Periprocedural Bleeding According to VARC-2 Criteria on 1-Year Clinical Outcomes in Patients After Transcatheter Aortic Valve Implantation. AB - There are differences in reporting bleeding complications after transcatheter aortic valve implantation (TAVI), which is a consequence of the lack of consensus for their definition. Furthermore, the amount of data on the impact of peri procedural bleeding on the mid-term prognosis is still limited. The aim of this study was to investigate the incidence, predictors, and impact of life threatening and major bleedings as defined by the Valve Academic Research Consortium 2 (VARC-2) in patients after TAVI over the mid-term prognosis.Consecutive patients who underwent TAVI from March 2010 to December 2013 were included. All data were classified according to the VARC-2 criteria. We assessed the incidence and the predictors of serious bleeding events (SBE), defined as life-threatening/disabling (LT/D) or major bleeding, and analyzed their impact on 30-day and 1-year clinical outcome.A total of 129 patients were included (79.1 +/- 8.3 years; mean EuroSCORE = 17.8 +/- 12.7). The SBE occurred in 25 patients (19.4%), of which 9 (7.0%) had LT/D and 16 (12.4%) had major bleeding. Trans-subclavian (TS) access (OR 4.38, 95% CI 2.13-14.29, P = 0.01) and diabetes (OR 2.93, 95% CI 1.08-7.93, P = 0.03) were identified as independent predictors of SBE. Patients with SBE had higher 30-day mortality (20.0% versus 4.0% P = 0.02) and 1-year mortality (40.0% versus 11.1%, P < 0.002). SBE independently predicted 1-year, all-cause mortality (HR 5.88, 95% CI 1.7319,94, P = 0.005).SBE are frequent after TAVI and are associated with decreased short and mid-term survival. Diabetes and TS access are independent risk factors for SBE. PMID- 26673440 TI - Low Stroke Rate of Carotid Stenosis Under the Guideline-Oriented Medical Treatment Compared With Surgical Treatment. AB - Medical treatment for asymptomatic carotid artery stenosis (ACAS) has advanced recently. The outcomes of medical treatment and surgical treatment were evaluated to clarify the optimal treatment for ACAS.Patients with ACAS of >= 50% luminal narrowing underwent serial follow-up carotid artery ultrasonography for one year or more at the Center for Cardiovascular Disease Prevention between November 2006 and October 2013. The incidence of cardiovascular events (stroke, myocardial infarction, cardiovascular death) was examined in 64 patients (medical treatment group), and in 47 patients (surgical group) who underwent surgical treatment (carotid endarterectomy or carotid artery stenting) during this same period at the Department of Neurosurgery.Annual cardiovascular event rate was 0.91% (2/219 person-year) in the group of guideline-oriented medical treatment with an annual check-up for disease management and 5.6% (6/107 person-year) in the surgical group (log-rank P = 0.027; HR in the medical treatment group, 0.19 [medical treatment/surgical]; 95% confidence interval [CI], 0.028 to 0.87). Annual stroke event rate was 0.46% (1/219 person-year) in the medical treatment group and 4.7% (5/107 personyear) in the surgical group (log-rank P = 0.016; HR in the medical treatment group, 0.11 [medical treatment/surgical]; 95% CI, 0.0057 to 0.70). Multivariate logistic analysis showed that the surgical group was an independent variable associated with cardiovascular events (P = 0.049).Annual cardiovascular and stroke event rates were low in patients receiving medical treatment for ACAS and better than surgical treatment. The present study shows that medical treatment is an important option for ACAS. PMID- 26673441 TI - Difference Between Dormant Conduction Sites Revealed by Adenosine Triphosphate Provocation and Unipolar Pace-Capture Sites Along the Ablation Line After Pulmonary Vein Isolation. AB - Dormant pulmonary vein (PV) conduction revealed by adenosine/adenosine triphosphate (ATP) provocation test and exit block to the left atrium by pacing from the PV side of the ablation line ("pace and ablate" method) are used to ensure durable pulmonary vein isolation (PVI). However, the mechanistic relation between ATP-provoked PV reconnection and the unexcitable gap along the ablation line is unclear.Forty-five patients with atrial fibrillation (AF) (paroxysmal: 31 patients, persistent: 14 patients; age: 61.1 +/- 9.7 years) underwent extensive encircling PVI (EEPVI, 179 PVs). After completion of EEPVI, an ATP provocation test (30 mg, bolus injection) and unipolar pacing (output, 10 mA; pulse width, 2 ms) were performed along the previous EEPVI ablation line to identify excitable gaps. Dormant conduction was revealed in 29 (34 sites) of 179 PVs (16.2%) after EEP-VI (22/45 patients). Pace capture was revealed in 59 (89 sites) of 179 PVs (33.0%) after EEPVI (39/45 patients), and overlapping sites, ie, sites showing both dormant conduction and pace capture, were observed in 22 of 179 (12.3%) PVs (17/45 patients).Some of the ATP-provoked dormant PV reconnection sites were identical to the sites with excitable gaps revealed by pace capture, but most of the PV sites were differently distributed, suggesting that the main underling mechanism differs between these two forms of reconnection. These findings also suggest that performance of the ATP provocation test followed by the "pace and ablate" method can reduce the occurrence of chronic PV reconnections. PMID- 26673442 TI - Plasma Pentraxin3 Level Is Associated With Plaque Vulnerability Assessed by Optical Coherence Tomography in Patients With Coronary Artery Disease. AB - The role of pentraxin 3 (PTX3) has been implicated in the process of plaque vulnerability. However, few studies have addressed the direct relationship between plaque morphology and plasma PTX3. We evaluated the relationship between coronary vulnerable plaque, assessed by optical coherence tomography (OCT), and plasma PTX3 in patients with coronary artery disease (CAD).OCT was used to determine plaque vulnerability in 51 patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS; n = 17) and stable angina (SA; n = 34). Both highly sensitive C-reactive protein and systemic plasma PTX3 were measured.Based on the OCT findings, patients were divided into 3 groups; a fibrous plaque (n = 18), thick-cap fibroatheroma (ThCFA) (n = 19), and thin-cap fibroatheroma (TCFA) (n = 14) groups. ThCFA was defined as a lipid-rich plaque (lipid content in >= 2 quadrant) covered with >= 65 MUm thick fibrous cap, and TCFA was that with < 65 MUm. There were no differences in patient characteristics between the 3 groups except for the presence of ACS and eicosapentaenoic acid levels. TCFA was more frequently observed with plaque rupture and intraluminal thrombus compared with the other 2 groups. Plasma PTX3 levels were higher in the TCFA group compared with the fibrous plaque and ThCFA groups, and showed weak correlation with cap thickness.Plasma PTX3 level was associated with plaque vulnerability assessed by OCT in patients with CAD. PMID- 26673443 TI - Predictors of Long-Term Mortality in Patients Hospitalized in an Intensive Cardiac Care Unit. AB - Patients admitted to an intensive cardiac care unit (ICCU) are a heterogeneous population with a high mortality rate. The aim of our study was to investigate which clinical, biochemical, and echocardiographic parameters routinely assessed may affect long-term mortality in a non-selected ICCU population.A total of 392 patients hospitalized between 2008-2011 (mean age, 70 +/- 13.8 years, 43% women) were consecutively and prospectively assessed with the following admission diagnoses: 168 with acute coronary syndromes (ACS), 122 with acute decompensated heart failure (ADHF), and 102 with other acute cardiac disorders. Patients were treated according to the current European Society of Cardiology (ESC) guidelines.During a mean 29.3 (+/- 18.9) months of observation, 152 (38.8%) patients died and 7.9% of the patients needed a red blood cell transfusion (RBC Tx). Patients who died were significantly older and had lower baseline levels of hemoglobin (Hb), serum iron concentration (SIC), total iron binding capacity (TIBC), cholesterol, and left ventricular ejection fraction (LVEF), as well as lower eGFR values, and higher white blood cell (WBC) counts and C-reactive protein (CRP) levels (P < 0.05). Predictors of death in multivariate regression analysis were age, Hb, LVEF, WBC, and CRP. The most powerful factor was hospitalization for non-ACS. The risk of long-term mortality increased with decreasing levels of Hb (P < 0.001), SIC (P = 0.001), TIBC (P = 0.009), and the need for RBC Tx (P < 0.001), as well as the diagnosis of ADHF (P < 0.001) and the absence of ACS (P = 0.007).In ICCU patients, age, Hb, parameters of iron status, and LVEF are strong predictors of long-term mortality. Among the ICCU population, patients with ACS diagnosis have better survival. PMID- 26673444 TI - Ultrasound Accelerated Thrombolysis May Be an Effective and Safe Treatment Modality for Intermediate Risk/Submassive Pulmonary Embolism. AB - Pulmonary embolism (PE) is a potentially life-threatening condition and the fact that 90% of PE originate from lower limb veins highlights the significance of early detection and treatment of deep vein thrombosis. Massive/high risk PE involving circulatory collapse or systemic arterial hypotension is associated with an early mortality rate of approximately 50%, in part from right ventricular (RV) failure. Intermediate risk/submassive PE, on the other hand, is defined as PE-related RV dysfunction, troponin and/or B-type natriuretic peptide elevation despite normal arterial pressure. Without prompt treatment, patients with intermediate risk PE may progress to the massive category with a potentially fatal outcome. In patients with PE and right ventricular dysfunction (RVD), in hospital mortality ranges from 5% to 17%, significantly higher than in patients without RVD. PMID- 26673445 TI - Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes. AB - Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene which encodes dystrophin protein. Dystrophin defect affects cardiac muscle as well as skeletal muscle. Cardiac dysfunction is observed in all patients with DMD over 18 years of age, but there is no curative treatment for DMD cardiomyopathy. To establish novel experimental platforms which reproduce the cardiac phenotype of DMD patients, here we established iPS cell lines from T lymphocytes donated from two DMD patients, with a protocol using Sendai virus vectors. We successfully conducted the differentiation of the DMD patient-specific iPS cells into beating cardiomyocytes. DMD patient-specific iPS cells and iPS cell-derived cardiomyocytes would be a useful in vitro experimental system with which to investigate DMD cardiomyopathy. PMID- 26673446 TI - Lymph nodes' evaluation in relation to colorectal cancer staging among African Americans. AB - BACKGROUND: Lymph nodes' examination in colorectal cancer (CRC) resection specimens is an important determinant that aids in the accuracy of CRC staging and treatment outcomes. Current guidelines call for the examination of at least 12 lymph nodes (LN) in resected specimens in order to establish accurate staging. AIM: To investigate lymph nodes' examination protocol as it relates to accurate CRC staging. METHODS: We reviewed 216 African American CRC patients from 1996 2013 who underwent CRC resection and met inclusion criteria for this study. The number of retrieved LNs, length of resected specimens, tumor grade, stage, location, size and histology were examined. RESULTS: The cohort study was made of 49% males, median age was 63 years and 45% of patients were at stage III and IV. The median (IQR) number of examined LNs was 15 (10-22) and the rate of patients with more than 12 examined LNs was 64%. There was a gradual increase in the percentage of patients with adequate number (>12) of examined LNs during the study period (from 60% in 1996-2000 to 84% in 2010-2013 period, P=0.014). Adequate LNs resection was neither associated with shift of stage from II to III (P=0.3) nor with the changes from stage IIIa to IIIc (P=0.9). Metastatic LNs were observed in 8% of samples with LNs (>12) vs. 13% of samples with <12 examined LNs (P=0.1). Patients that had pre-surgical treatment (chemotherapy and radiotherapy) before surgery had <12 LNs examined. There was also a trend of having more examined lymph nodes in large tumors. CONCLUSIONS: Our study shows that there has been an increase in the number of lymph nodes examined in CRC resections since the advent of the current quality initiative. However this increase does not seem to affect the stage or percentage of metastatic lymph nodes' detection in CRC patients. PMID- 26673447 TI - Prevalence and features of colorectal lesions among Hispanics: A hospital-based study. AB - AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma >= 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using chi(2) statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID- 26673448 TI - Outer membrane protein OmpQ of Bordetella bronchiseptica is required for mature biofilm formation. AB - Bordetella bronchiseptica, an aerobic Gram-negative bacterium, is capable of colonizing the respiratory tract of diverse animals and chronically persists inside the hosts by forming biofilm. Most known virulence factors in Bordetella species are regulated by the BvgAS two-component transduction system. The Bvg activated proteins play a critical role during host infection. OmpQ is an outer membrane porin protein which is expressed under BvgAS control. Here, we studied the contribution of OmpQ to the biofilm formation process by B. bronchiseptica. We found that the lack of expression of OmpQ did not affect the growth kinetics and final biomass of B. bronchiseptica under planktonic growth conditions. The DeltaompQ mutant strain displayed no differences in attachment level and in early steps of biofilm formation. However, deletion of the ompQ gene attenuated the ability of B. bronchiseptica to form a mature biofilm. Analysis of ompQ gene expression during the biofilm formation process by B. bronchiseptica showed a dynamic expression pattern, with an increase of biofilm culture at 48 h. Moreover, we demonstrated that the addition of serum anti-OmpQ had the potential to reduce the biofilm biomass formation in a dose-dependent manner. In conclusion, we showed for the first time, to the best of our knowledge, evidence of the contribution of OmpQ to a process of importance for B. bronchiseptica pathobiology. Our results indicate that OmpQ plays a role during the biofilm development process, particularly at later stages of development, and that this porin could be a potential target for strategies of biofilm formation inhibition. PMID- 26673450 TI - Pleomorphic Adenoma of Cheek Masquerading as Fibrolipoma - Case Report with Review. AB - Salivary gland tumours are rare, comprising 3% of head and neck tumours, of which Pleomorphic Adenoma (PA) constitutes 70-80%. It accounts for 53-74% of parotid tumours, 44-68% submandibular gland tumours and 38-43% of minor salivary gland tumours. It usually presents as painless, firm, slow growing mobile mass. Various diagnostic modalities for early detection of the tumour include FNAC, Ultrasonography, CT and MRI. The choice of treatment of pleomorphic adenoma of the minor salivary glands depends on the aggressiveness of the tumour, the extension of the mass, and its relation with the vital structures. Here, we report a rare case of pleomorphic adenoma of minor salivary glands of cheek in a 40-year-old male patient with emphasis on various diagnostic modalities. PMID- 26673449 TI - Interplay between plasmon and single-particle excitations in a metal nanocluster. AB - Plasmon-generated hot carriers are used in photovoltaic or photochemical applications. However, the interplays between the plasmon and single-particle excitations in nanosystems have not been theoretically addressed using ab initio methods. Here we show such interplays in a Ag55 nanocluster using real-time time dependent density functional theory simulations. We find that the disappearance of the zero-frequency peak in the Fourier transform of the band-to-band transition coefficient is a hallmark of the plasmon. We show the importance of the d-states for hot-carrier generations. If the single-particle d-to-s excitations are resonant to the plasmon frequency, the majority of the plasmon energy will be converted into hot carriers, and the overall hot-carrier generation is enhanced by the plasmon; if such resonance does not exist, we observe an intriguing Rabi oscillation between the plasmon and hot carriers. Phonons play a minor role in plasmonic dynamics in such small systems. This study provides guidance on improving plasmonic applications. PMID- 26673452 TI - A Rapid Colorimetric Sensor of Clenbuterol Based on Cysteamine-Modified Gold Nanoparticles. AB - Demonstrated was a simple visual and rapid colorimetric sensor for detection of clenbuterol (CLB) based on gold nanoparticles (AuNPs) modified with cysteamine (CA) and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-vis. The solution color from red to blue gray with increasing clenbuterol concentration resulted from the aggregation of AuNPs. The detection limit of clenbuterol is 50 nM by naked eyes. The selectivity of CA AuNPs detection system for clenbuterol is excellent compared with other interferents in food. This sensor has been successfully applied to detect clenbuterol in real blood sample. PMID- 26673451 TI - Matrix Metalloproteinase-2 Knockout and Heterozygote Mice Are Protected from Hydronephrosis and Kidney Fibrosis after Unilateral Ureteral Obstruction. AB - Matrix Metalloproteinase-2 (Mmp2) is a collagenase known to be important in the development of renal fibrosis. In unilateral ureteral obstruction (UUO) the obstructed kidney (OK) develops fibrosis, while the contralateral (CL) does not. In this study we investigated the effect of UUO on gene expression, fibrosis and pelvic remodeling in the kidneys of Mmp2 deficient mice (Mmp2-/-), heterozygous animals (Mmp2+/-) and wild-type mice (Mmp2+/+). Sham operated animals served as controls (Cntrl). UUO was prepared under isoflurane anaesthesia, and the animals were sacrificed after one week. UUO caused hydronephrosis, dilation of renal tubules, loss of parenchymal thickness, and fibrosis. Damage was most severe in Mmp2+/+ mice, while both Mmp2-/- and Mmp2+/- groups showed considerably milder hydronephrosis, no tubular necrosis, and less tubular dilation. Picrosirius red quantification of fibrous collagen showed 1.63+/-0.25% positivity in OK and 0.29+/-0.11% in CL (p<0.05) of Mmp2+/+, Mmp2-/- OK and Mmp2-/- CL exhibited only 0.49+/-0.09% and 0.23+/-0.04% (p<0.05) positivity, respectively. Mmp2+/- OK and Mmp2+/- CL showed 0.43+/-0.09% and 0.22+/-0.06% (p<0.05) positivity, respectively. Transcriptomic analysis showed that 26 genes (out of 48 examined) were differentially expressed by ANOVA (p<0.05). 25 genes were upregulated in Mmp2+/+ OK compared to Mmp2+/+ CL: Adamts1, -2, Col1a1, -2, -3a1, -4a1, -5a1, 5a2, Dcn, Fbln1, -5, Fmod, Fn1, Itga2, Loxl1, Mgp, Mmp2, -3, Nid1, Pdgfb, Spp1, Tgfb1, Timp2, Trf, Vim. In Mmp2-/- and Mmp2+/- 18 and 12 genes were expressed differentially between OK and CL, respectively. Only Mmp2 was differentially regulated when comparing Mmp2-/- OK and Mmp2+/- OK. Under stress, it appears that Mmp2+/- OK responds with less Mmp2 upregulation than Mmp2+/+ OK, suggesting that there is a threshold level of Mmp2 necessary for damage and fibrosis to occur. In conclusion, reduced Mmp2 expression during UUO protects mice against hydronephrosis and renal fibrosis. PMID- 26673453 TI - Evaluating predictive screening for children's post-injury mental health: New data and a replication. AB - BACKGROUND: Recommended approaches for secondary prevention of posttrauma mental health difficulties in children require empirically sound predictive screening to determine which children require more intensive monitoring or targeted intervention. Although there are several promising screening tools for injured children, none has emerged as the gold standard, and little replication data are available regarding their performance. OBJECTIVE: To evaluate a predictive screening protocol for risk of later posttraumatic stress (PTS) and depression outcomes and address a crucial lack of replication studies by examining performance of two previously published screening tools (Screening Tool for Early Predictors of PTSD [STEPP] and Child Trauma Screening Questionnaire [CTSQ]). METHOD: The study enrolled 290 children hospitalized after acute injury. A three part screening protocol, including acute PTS and depression symptoms and other empirically derived risk factors, was administered in hospital as part of a stepped care study. PTS and depression symptoms and health-related quality of life (HRQoL) were assessed 6 months post-injury. PMID- 26673454 TI - NICE rejects trastuzumab emtansine for use on NHS. PMID- 26673455 TI - Acute Kidney Injury Care Bundles. AB - Acute kidney injury (AKI) is a common complication that occurs in hospitalized patients and appears susceptible to a wide variability in practice. This may lead to suboptimal quality of care. The concept of a 'care bundle' for AKI has been proposed to improve the reliability and quality of care. A bundle is designed to be a structured method of improving care processes and outcomes. It contains a small set of evidence-based practices intended for a defined population and care setting. The Institute for Healthcare Improvement has developed guidelines for the design of care bundles. Care bundles for critically ill patients focusing on mechanical ventilation, central venous catheters, and sepsis have been widely implemented with modest success in terms of compliance and impact on care processes and outcomes. A care bundle for AKI is highly desired, given the observed practice variation and indication of poor care for AKI patients; however, existing proposals are too comprehensive and have not been focused on a defined population at-risk, clinical context or setting. They have also not engaged local stakeholders in the process. PMID- 26673456 TI - The assessment of usefulness of the qualification card and ultrasonographic consultation. PMID- 26673458 TI - Pre-test probability risk scores and their use in contemporary management of patients with chest pain: One year stress echo cohort study. AB - OBJECTIVES: To compare how patients with chest pain would be investigated, based on the two guidelines available for UK cardiologists, on the management of patients with stable chest pain. The UK National Institute of Clinical Excellence (NICE) guideline which was published in 2010 and the European society of cardiology (ESC) guideline published in 2013. Both guidelines utilise pre-test probability risk scores, to guide the choice of investigation. DESIGN: We undertook a large retrospective study to investigate the outcomes of stress echocardiography. SETTING: A large tertiary centre in the UK in a contemporary clinical practice. PARTICIPANTS: Two thirds of the patients in the cohort were referred from our rapid access chest pain clinics. RESULTS: We found that the NICE risk score overestimates risk by 20% compared to the ESC Risk score. We also found that based on the NICE guidelines, 44% of the patients presenting with chest pain, in this cohort, would have been investigated invasively, with diagnostic coronary angiography. Using the ESC guidelines, only 0.3% of the patients would be investigated invasively. CONCLUSION: The large discrepancy between the two guidelines can be easily reduced if NICE adopted the ESC risk score. PMID- 26673457 TI - A steroid metabolizing gene variant in a polyfactorial model improves risk prediction in a high incidence breast cancer population. AB - BACKGROUND: We have combined functional gene polymorphisms with clinical factors to improve prediction and understanding of sporadic breast cancer risk, particularly within a high incidence Caucasian population. METHODS: A polyfactorial risk model (PFRM) was built from both clinical data and functional single nucleotide polymorphism (SNP) gene candidates using multivariate logistic regression analysis on data from 5022 US Caucasian females (1671 breast cancer cases, 3351 controls), validated in an independent set of 1193 women (400 cases, 793 controls), and reassessed in a unique high incidence breast cancer population (165 cases, 173 controls) from Marin County, CA. RESULTS: The optimized PFRM consisted of 22 SNPs (19 genes, 6 regulating steroid metabolism) and 5 clinical risk factors, and its 5-year and lifetime risk prediction performance proved significantly superior (~ 2-fold) over the Gail model (Breast Cancer Risk Assessment Tool, BCRAT), whether assessed by odds (OR) or positive likelihood (PLR) ratios over increasing model risk levels. Improved performance of the PFRM in high risk Marin women was due in part to genotype enrichment by a CYP11B2 ( 344T/C) variant. CONCLUSIONS AND GENERAL SIGNIFICANCE: Since the optimized PFRM consistently outperformed BCRAT in all Caucasian study populations, it represents an improved personalized risk assessment tool. The finding of higher Marin County risk linked to a CYP11B2 aldosterone synthase SNP associated with essential hypertension offers a new genetic clue to sporadic breast cancer predisposition. PMID- 26673459 TI - Pathogenic Microorganisms and Pancreatic Cancer. AB - BACKGROUND: Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Established risk factors for pancreatic cancer, including smoking, chronic pancreatitis, obesity and type 2 diabetes mellitus, collectively account for less than half of all pancreatic cancer cases. Accumulating reports have demonstrated that there is an association between pathogenic microorganisms and pancreatic cancer. SUMMARY: A substantial amount of preclinical and clinical evidence suggests that microbiota are likely to influence pancreatic carcinogenesis. This review summarizes the literature on studies examining infections that have been linked to pancreatic cancer. KEY MESSAGE: Helicobacter pylori infection may be a risk factor for pancreatic cancer; chronic hepatitis virus and oral microbiota may also play a role in pancreatic carcinogenesis. PRACTICAL IMPLICATIONS: Considering the worldwide burden of the disease, the association between microbiota and pancreatic cancer in this review may provide new ideas to prevent and treat pancreatic cancer more efficiently. Further studies in this direction are urgently needed. PMID- 26673460 TI - Racial Composition Over the Life Course: Examining Separate and Unequal Environments and the Risk for Heart Disease for African American Men. AB - PURPOSE: Studies have demonstrated the effects of segregated social and physical environments on the development of chronic diseases for African Americans. Studies have not delineated the effects of segregated environments specifically on the health of African American men over their lifetime. This study examines the relationship between life course measures of racial composition of social environments and diagnosis of hypertension among African American men. DESIGN: We analyzed cross-sectional data from a convenience sample of African American men seeking health care services in an outpatient primary care clinic serving a medically underserved patient population (N=118). Multivariable logistic regression analyses were used to examine associations between racial composition of multiple environments across the life course (eg, junior high school, high school, neighborhood growing up, current neighborhood, place of employment, place of worship) and hypertension diagnosis. RESULTS: The majority (86%) of participants were not currently in the workforce (retired, unemployed, or disabled) and more than half (54%) reported an annual household income of <$9,999; median age was 53. Results suggest that African American men who grew up in mostly Black neighborhoods (OR=4.3; P=.008), and worked in mostly Black environments (OR=3.1; P=.041) were more likely to be diagnosed with hypertension than those who did not. CONCLUSION: We found associations between mostly Black residential and workplace settings and hypertension diagnoses among African American men. Findings suggest exposure to segregated environments during childhood and later adulthood may impact hypertension risk among African American men over the life course. PMID- 26673461 TI - Design of High-Affinity Stapled Peptides To Target the Repressor Activator Protein 1 (RAP1)/Telomeric Repeat-Binding Factor 2 (TRF2) Protein-Protein Interaction in the Shelterin Complex. AB - Shelterin, a six-protein complex, plays a fundamental role in protecting both the length and the stability of telomeres. Repressor activator protein 1 (RAP1) and telomeric repeat-binding factor 2 (TRF2) are two subunits in shelterin that interact with each other. Small-molecule inhibitors that block the RAP1/TRF2 protein-protein interaction can disrupt the structure of shelterin and may be employed as pharmacological tools to investigate the biology of shelterin. On the basis of the cocrystal structure of RAP1/TRF2 complex, we have developed first-in class triazole-stapled peptides that block the protein-protein interaction between RAP1 and TRF2. Our most potent stapled peptide binds to RAP1 protein with a Ki value of 7 nM and is >100 times more potent than the corresponding wild-type TRF2 peptide. On the basis of our high-affinity peptides, we have developed and optimized a competitive, fluorescence polarization (FP) assay for accurate and rapid determination of the binding affinities of our designed compounds and this assay may also assist in the discovery of non-peptide, small-molecule inhibitors capable of blocking the RAP1/TRF2 protein-protein interaction. PMID- 26673462 TI - Understanding the Role of Public Administration in Implementing Action on the Social Determinants of Health and Health Inequities. AB - Many of the societal level factors that affect health - the 'social determinants of health (SDH)' - exist outside the health sector, across diverse portfolios of government, and other major institutions including non-governmental organisations (NGOs) and the private sector. This has created growing interest in how to create and implement public policies which will drive better and fairer health outcomes. While designing policies that can improve the SDH is critical, so too is ensuring they are appropriately administered and implemented. In this paper, we draw attention to an important area for future public health consideration - how policies are managed and implemented through complex administrative layers of 'the state.' Implementation gaps have long been a concern of public administration scholarship. To precipitate further work in this area, in this paper, we provide an overview of the scholarly field of public administration and highlight its role in helping to understand better the challenges and opportunities for implementing policies and programs to improve health equity. PMID- 26673463 TI - Rights Language in the Sustainable Development Agenda: Has Right to Health Discourse and Norms Shaped Health Goals? AB - While the right to health is increasingly referenced in Sustainable Development Goal (SDG) discussions, its contribution to global health and development remains subject to considerable debate. This hypothesis explores the potential influence of the right to health on the formulation of health goals in 4 major SDG reports. We analyse these reports through a social constructivist lens which views the use of rights rhetoric as an important indicator of the extent to which a norm is being adopted and/or internalized. Our analysis seeks to assess the influence of this language on goals chosen, and to consider accordingly the potential for rights discourse to promote more equitable global health policy in the future. PMID- 26673464 TI - Compliance With Guideline Statements for Urethral Catheterization in an Iranian Teaching Hospital. AB - BACKGROUND: It is believed that healthcare staff play an important role in minimizing complications related to urethral catheterization. The purpose of this study was to determine whether or not healthcare staff complied with the standards for urethral catheterization. METHODS: This study was conducted in Imam Reza teaching hospital, Tabriz, Iran, from July to September 2013. A total of 109 catheterized patients were selected randomly from surgical and medical wards and intensive care units (ICUs). A questionnaire was completed by healthcare staff for each patient to assess quality of care provided for catheter insertion, while catheter in situ, draining and changing catheter bags. Items of the questionnaire were obtained from guidelines for the prevention of infection. Data analysis was performed with SPSS 16. RESULTS: The mean age of the patients was 50.54+/-22.13. Of the 109 patients, 56.88% were admitted to ICUs. The mean duration of catheter use was 15.86 days. Among the 25 patients who had a urinalysis test documented in their hospital records, 11 were positive for urinary tract infection (UTI). The lowest rate of hand-washing was reported before bag drainage (49.52%). The closed drainage catheter system was not available at all. Among the cases who had a daily genital area cleansing, in 27.63% cases, the patients or their family members performed the washing. In 66.35% of cases, multiple-use lubricant gel was applied; single-use gel was not available. The rate of documentation for bag change was 79%. CONCLUSION: The majority of the guideline statements was adhered to; however, some essential issues, such as hand hygiene were neglected. And some patients were catheterized routinely without proper indication. Limiting catheter use to mandatory situations and encouraging compliance with guidelines are recommended. PMID- 26673465 TI - Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters. AB - BACKGROUND: For the purpose of understanding the Food and Drug Administration's (FDA's) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. METHODS: The FDA's warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. RESULTS: Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. CONCLUSION: Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus begun to keep tabs on social media promotions of prescription drugs. PMID- 26673466 TI - Biopharmaceutical Innovation System in China: System Evolution and Policy Transitions (Pre-1990s-2010s). AB - BACKGROUND: This article sets up the initial discussion of the evolution of biopharmaceutical innovation in China through the perspective of sectoral innovation system (SIS). METHODS: Two data sources including archival documentary data and field interviews were used in this study. Archival documentary data was collected from China Food and Drug Administration (CFDA) and Chinese National Knowledge Infrastructure (CNKI). In addition, industrial practitioners and leading researchers in academia were interviewed. RESULTS: Biopharmaceutical in China was established through international knowledge transfer. The firms played more active role in commercializing biopharmaceutical in China though universities and research institutes were starting to interact with local firms and make contribution to biopharmaceutical industrialization. The transition of the Chinese government's policies continuously shapes the evolution of biopharmaceutical sector. Policies have been dramatic changes before and after 1980s to encourage developing biopharmaceutical as a competitive industry for China. CONCLUSION: A SIS for biopharmaceutical has been shaped in China. However, currently biopharmaceutical is still a small sector in China, and for the further growth of the industry more synthetic policies should be implemented. Not only the policy supports towards the research and innovation of biopharmaceuticals in the early stage of development should be attended, but also commercialization of biopharmaceutical products in the later stage of sales. PMID- 26673467 TI - James Bond and Global Health Diplomacy. AB - In the 21st Century, distinctions and boundaries between global health, international politics, and the broader interests of the global community are harder to define and enforce than ever before. As a result, global health workers, leaders, and institutions face pressing questions around the nature and extent of their involvement with non-health endeavors, including international conflict resolution, counter-terrorism, and peace-keeping, under the global health diplomacy (GHD) paradigm. PMID- 26673468 TI - Middle Age Like Fight or Modern Symbiosis? Comment on "Substitutes or Complements? Diagnosis and Treatment With Non-conventional and Conventional Medicine". AB - Complementary and alternative medicine (CAM) is widely used by patients worldwide. Financial factors may influence the decision to use CAM. National Health Systems are requested to consider CAM in their health plans. PMID- 26673469 TI - Policy Capacity Is Necessary but Not Sufficient Comment on "Health Reform Requires Policy Capacity". AB - Policy capacity focuses on the managerial and organizational abilities to inform policy decisions with sound research and analysis, and facilitate policy implementation with operational efficiency. It stems from a view of the policy process that is rational and positivistic, in which optimal policy choices can be identified, selected, and implemented with objectivity. By itself, however, policy capacity neglects the political aspects of policy-making that can dominate the process, even in health policies. These technical capabilities are certainly needed to advance reforms in health policies, but they are not sufficient. Instead, they must be complemented with public engagement and policy advocacy to ensure support from the public that policies are meant to serve. PMID- 26673470 TI - Policy Capacity in the Learning Healthcare System Comment on "Health Reform Requires Policy Capacity". AB - Pierre-Gerlier Forest and his colleagues make a strong argument for the need to expand policy capacity among healthcare actors. In this commentary, I develop an additional argument in support of Forest et al view. Forest et al rightly point to the need to have embedded policy experts to successfully translate healthcare reform policy into healthcare change. Translation of externally generated innovation policy into local solutions is only one source of healthcare system change. We also need to build learning healthcare systems that can discover new health solutions at the frontline of care. Enhanced policy capacity staffing in those organizations will be key to building continuously learning health systems. PMID- 26673471 TI - An Untapped Resource: Patient and Public Involvement in Implementation Comment on "Knowledge Mobilization in Healthcare Organizations: A View From the Resource Based View of the Firm". AB - This commentary considers the potential role of patient and public involvement in implementation. Developing an analytical thread from the resource-based view of the Firm, we argue that this involvement may create unique resources that have the capacity to enhance the impact of implementation activity for healthcare organisations. PMID- 26673472 TI - Balancing Management and Leadership in Complex Health Systems Comment on "Management Matters: A Leverage Point for Health Systems Strengthening in Global Health". AB - Health systems, particularly those in low- and middle-income countries (LMICs), need stronger management and leadership capacities. Management and leadership are not synonymous, yet should be considered together as there can be too much of one and not enough of the other. In complex adaptive health systems, the multiple interactions and relationships between people and elements of the system mean that management and leadership, so often treated as domains of the individual, are additionally systemic phenomena, emerging from these relational interactions. This brief commentary notes some significant implications for how we can support capacity strengthening interventions for complex management and leadership. These would necessarily move away from competency-based models focused on training for individuals, and would rather encompass longer-term initiatives explicitly focused on systemic goals of accountability, innovation, and learning. PMID- 26673473 TI - The Pill vs. the Sword: Additional Considerations Comment on "The Pill Is Mightier Than the Sword". AB - In this paper, I present additional information for policy-makers and researchers to consider in response to the view proposed by Potts et al that "the pill is mightier than the sword." I identify states with both high rates of terrorism and a youth bulge and discuss correlates of both these societal characteristics. The research examined supports the view that factors other than access to family planning are more important in facilitating terrorism. PMID- 26673474 TI - Interregional Patient Mobility in the Italian NHS: A Case of Badly-Managed Decentralization Comment on "Regional Incentives and Patient Cross-Border Mobility: Evidence From the Italian Experience". AB - The article by Brenna and Spandonaro on interregional mobility for acute hospital care in Italy raises important issues concerning social and territorial equity in a healthcare system. Based on Regions and private providers' strategic behavior, the hypothesis adopted to explain patient cross-border mobility (CBM), demonstrated by statistical analysis, may be further explored using qualitative methods. In order to reduce CBM, the central government needs to play a more active role in coordination, even in a highly decentralized National Health Service (NHS). PMID- 26673475 TI - Management Education in Public Health: Further Considerations Comment on "Management Matters: A Leverage Point for Health Systems Strengthening in Global Health". AB - Knowing and applying the basic management functions of planning, organizing, staffing, directing, and controlling, as well as their permutations and combinations, are vital to effective delivery of public health services. Presently, graduate programs that prepare public health professionals neither emphasize teaching management theory, nor its application. This deficit puts those who become managers in public health and those they serve at a distinct disadvantage. This deficit can be remedied by enhanced teaching of management subjects. PMID- 26673476 TI - Necessary but Not Sufficient... Comment on "Knowledge Mobilization in Healthcare Organizations: A View From the Resource-Based View of the Firm". AB - The challenge of mobilizing knowledge to improve patient care, population health and ensure effective use of resources is an enduring one in healthcare systems across the world. This commentary reflects on an earlier paper by Ferlie and colleagues that proposes the resource-based view (RBV) of the firm as a useful theoretical lens through which to study knowledge mobilization in healthcare. Specifically, the commentary considers 3 areas that need to be addressed in relation to the proposed application of RBV: the definition of competitive advantage in healthcare; the contribution of macro level theory to understanding knowledge mobilization in healthcare; and the need to embrace and align multiple theories at the micro, meso, and macro levels of implementation. PMID- 26673477 TI - Moving Toward Universal Health Coverage (UHC) to Achieve Inclusive and Sustainable Health Development: Three Essential Strategies Drawn From Asian Experience Comment on "Improving the World's Health Through the Post-2015 Development Agenda: Perspectives from Rwanda". AB - Binagwaho and colleagues' perspective piece provided a timely reflection on the experience of Rwanda in achieving the Millennium Development Goals (MDGs) and a proposal of 5 principles to carry forward in post-2015 health development. This commentary echoes their viewpoints and offers three lessons for health policy reforms consistent with these principles beyond 2015. Specifically, we argue that universal health coverage (UHC) is an integrated solution to advance the global health development agenda, and the three essential strategies drawn from Asian countries' health reforms toward UHC are: (1) Public financing support and sequencing health insurance expansion by first extending health insurance to the extremely poor, vulnerable, and marginalized population are critical for achieving UHC; (2) Improved quality of delivered care ensures supply-side readiness and effective coverage; (3) Strategic purchasing and results-based financing creates incentives and accountability for positive changes. These strategies were discussed and illustrated with experience from China and other Asian economies. PMID- 26673478 TI - What Money Cannot Buy? Compassion in Healthcare: A Response to the Recent Commentaries. PMID- 26673480 TI - Synthesis of [Pt(SnBu(t)3)(IBu(t))(MU-H)]2, a Coordinatively Unsaturated Dinuclear Compound which Fragments upon Addition of Small Molecules to Form Mononuclear Pt-Sn Complexes. AB - The reaction of Pt(COD)2 with one equivalent of tri-tert-butylstannane, Bu(t)3SnH, at room temperature yields Pt(SnBu(t)3)(COD)(H)(3) in quantitative yield. In the presence of excess Bu(t)3SnH, the reaction goes further, yielding the dinuclear bridging stannylene complex [Pt(SnBu(t)3)(MU-SnBu(t)2)(H)2]2 (4). The dinuclear complex 4 reacts rapidly and reversibly with CO to furnish [Pt(SnBu(t)3)(MU-SnBu(t)2)(CO)(H)2]2 (5). Complex 3 reacts with N,N'-di-tert butylimidazol-2-ylidene, IBu(t), at room temperature to give the dinuclear bridging hydride complex [Pt(SnBu(t)3)(IBu(t))(MU-H)]2 (6). Complex 6 reacts with CO, C2H4, and H2 to give the corresponding mononuclear Pt complexes Pt(SnBu(t)3)(IBu(t))(CO)(H)(7), Pt(SnBu(t)3)(IBu(t))(C2H4)(H)(8), and Pt(SnBu(t)3)(IBu(t))(H)3 (9), respectively. The reaction of IBu(t) with the complex Pt(SnBu(t)3)2(CO)2 (10) yielded an abnormal Pt-carbene complex Pt(SnBu(t)3)2(aIBu(t))(CO) (11). DFT computational studies of the dimeric complexes [Pt(SnR3)(NHC)(MU-H)]2, the potentially more reactive monomeric complexes Pt(SnR3)(NHC)(H) and the trihydride species Pt(SnBu(t)3)(IBu(t))(H)3 have been performed, for NHC = IMe and R = Me and for NHC = IBu(t) and R = Bu(t). The structures of complexes 3-8 and 11 have been determined by X-ray crystallography and are reported. PMID- 26673479 TI - Integrating complementary/alternative medicine into primary care: evaluating the evidence and appropriate implementation. AB - The frequency with which patients utilize treatments encompassed by the term complementary/alternative medicine (CAM) is well documented. A number of these therapies are beginning to be integrated into contemporary medical practice. This article examines three of them: osteopathic manipulation, yoga, and acupuncture, with a focus on their physiological effects, efficacy in treating medical conditions commonly encountered by practitioners, precautions or contraindications, and ways in which they can be incorporated into clinical practice. Physicians should routinely obtain information about use of CAM as part of their patient history and should consider their role based on physiological effects and clinical research results. PMID- 26673481 TI - Aggression behavior and substance use among immigrant children: Mediating effect of antisocial attitudes. AB - In 2010, approximately one out of four youths in the United States were immigrant children. Hispanics and Asians comprised the largest groups (58% and 16%), respectively. Today, the Hispanic population is the largest ethnic minority in the United States (15%) and is a majority of the U.S. foreign-born population (47%). While immigration is a positive process for most immigrants, resettlement into a new country has challenges, including acculturation adjustments. Youth engage in risky behaviors such as substance use and antisocial behaviors. For immigrant youth with limited supportive opportunities, however, the acculturation process can be difficult. Stress, alienation, and stigma often manifest and cause behavioral problems, including aggression. This pilot study examines the mediating effect of antisocial attitudes using sociocultural, developmental, and environmental factors to understand Hispanic youth problem behaviors. We sampled 136 youths, ages 6-12, from predominantly Hispanic elementary schools in the southwestern United States to ascertain the role of aggression and antisocial behavior in substance use attitudes. The results show significant differences in aggression, antisocial attitudes, and substance use according to (1) age, (2) years in the United States, (3) English level, and (4) relationship with mother. Aggression significantly predicted antisocial attitudes and substance use, with antisocial attitudes having a mediating effect on the relationship between aggression and substance use. In developing social service programs to prevent substance use among children from immigrant families, social work educators and practitioners may consider addressing the role of aggression in Hispanic adolescents' future behavior. PMID- 26673482 TI - Malignant Duodeno-Colic Fistula: A Rare Complication of Colorectal Cancer. PMID- 26673483 TI - Effect of Evacuation on Body Weight After the Great East Japan Earthquake. AB - INTRODUCTION: The Great East Japan Earthquake occurred on March 11, 2011, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The government ordered a mandatory evacuation from the high radioactive concentration area in Fukushima, which might have forced many evacuees to change particular aspects of their lifestyles. This study assessed the hypothesis that mean body weight and the proportion of overweight/obese individuals would increase among evacuees after versus before the disaster. METHODS: A longitudinal study examined data collected from 41,633 Japanese participants (mean age, 67 years) sourced from general health checkups conducted in 13 communities between 2008 and 2010. Follow-up examinations were conducted from June 2011 through March 2013. RESULTS: A total of 27,486 participants (12,432 men and 15,054 women; follow-up proportion, 66%) received follow-up examinations after the disaster, with an average follow-up of 1.6 years. Mean body weight significantly increased in both evacuees (n=9,671) and non-evacuees (n=17,815) after the disaster, with greater changes in body weight among evacuees than non-evacuees (+1.2 kg vs +0.3 kg, p<0.001). The proportion of overweight/obese people also increased among evacuees after the disaster, and evacuation was associated with an increased risk of being overweight, despite adjustments for confounding variables. The proportions of overweight evacuees before and after the disaster were 31.8% and 39.4%, respectively, whereas proportions among non-evacuees were 28.3% and 30.3%, respectively. CONCLUSIONS: Body weight and the proportion of overweight/obese people increased among residents, especially evacuees, in the evacuation zone of Fukushima prefecture after the Great East Japan Earthquake. PMID- 26673486 TI - Image of the month: Pseudomelanosis duodeni and Strongyloides stercoralis. PMID- 26673484 TI - Gauging the Effect of U.S. Tobacco Control Policies From 1965 Through 2014 Using SimSmoke. AB - INTRODUCTION: The year 2014 marked the 50th Anniversary of the first Surgeon General's Report. This paper estimates the effect of tobacco control policies in the U.S. after the 1964 Report using the SimSmoke tobacco control simulation model. METHODS: SimSmoke uses National Health Interview Survey data from 1965 through 2012 on smoking prevalence, initiation, and cessation rates, and incorporates policies implemented since 1965. The model projects smoking prevalence and smoking-attributable deaths (SADs) from 1965 through 2065 and is validated against National Health Interview Survey data. Counterfactual scenarios with policies constant since 1965 and with individual policies are estimated. Analysis was conducted in February 2014. RESULTS: SimSmoke generally validated well during the time period from 1965 through 2012. As a result of all policies, smoking prevalence is estimated to have fallen by almost 55% by 2014, with a total of 2 million SADs averted from 1965 through 2014, increasing to 20.1 million SADs by 2065. The Fairness Doctrine is estimated to have reduced adult smoking prevalence by about 24% by 2014 and averted 10.4 million SADs by 2065, while price increases reduced smoking prevalence by 24% by 2014 and averted 7.3 million SADs by 2065. Smoke-free air laws, cessation treatment, and tobacco control spending individually reduced smoking rates by 3%-5.5% by 2014. CONCLUSIONS: By 2014, SimSmoke predicts a 53% reduction in smoking rates and almost 2 million SADs averted due to polices implemented since the 1964 Surgeon General's Report, with most of the health benefit still to occur in future years. PMID- 26673487 TI - Image of the month: Stercoral Colitis. PMID- 26673488 TI - Image of the month: A Red Ball at the Base of the Cecum. PMID- 26673489 TI - Image of the month: A Rare Cause of Upper GI Bleeding: Metastatic Implantation at a Percutaneous Endoscopic Gastrostomy Site Presenting as a Bleeding Gastric Mass. PMID- 26673490 TI - Image of the month: Histoplasmosis of the Small Bowel Acquired While Camping. PMID- 26673491 TI - Image of the month: A Rare Case of Superior Mesenteric Artery Syndrome Causing Upper Gastrointestinal Bleeding. PMID- 26673492 TI - Image of the month: Classic Appearance of a Traditional Serrated Adenoma. PMID- 26673493 TI - Image of the month: Disseminated Nontuberculous Mycobacteriosis. PMID- 26673494 TI - Video of the Month: Transrectal Gallbladder-Preserving Cholecystolithotomy via Pure Natural Orifice Transluminal Endoscopic Surgery: First Time in Humans. PMID- 26673497 TI - Defining the Risk of Small Polyps: Potential Value of CTC. AB - Although the clinical importance of large colorectal polyps and the benign nature of diminutive polyps are generally accepted, elucidating the clinical significance of small polyps (6-9 mm) could have an enormous impact on colorectal cancer (CRC) screening. Serial volumetric measurement via CTC may be a valuable method for assessing changes in polyp size. With the recognition of alternative CRC pathways, a more precise understanding of the natural history of small colorectal polyps is needed and data such as those reported by Nolthenius contribute to that knowledge. PMID- 26673500 TI - Reply to Jia. PMID- 26673501 TI - A Misleading Reference for Fecal Microbiota Transplant. PMID- 26673502 TI - Utility of Fecal Markers to Diagnose and Monitor Inflammatory Bowel Diseases. PMID- 26673503 TI - ACG Guidelines on Management of PTEN-Hamartoma Tumor Syndrome: Does the Evidence Support so Much so Young? PMID- 26673504 TI - Response to Sorrentino et al. PMID- 26673505 TI - Response to Editorial of Peter D.R. Higgins (July 2015). PMID- 26673506 TI - Response to Laine et al. PMID- 26673507 TI - Pilocarpine Hydrochloride Improves Baseline Image of Magnetic Resonance Cholangiopancreatography. PMID- 26673508 TI - Antibodies to Mitotic Apparatus: New Association With Cholestatic Liver Disease. PMID- 26673509 TI - Vedolizumab and Infliximab Combination Therapy in the Treatment of Crohn's Disease. PMID- 26673510 TI - Refractory Peristomal Pyoderma Gangrenosum Successfully Treated With Intravenous Immunoglobulin: A Case Report. PMID- 26673511 TI - The Susceptibility of Celiac Disease Intestinal Microbiota to Clostridium difficile Infection. PMID- 26673513 TI - Corrigendum: Amyloidosis of Duodenum. PMID- 26673514 TI - Corrigendum: Multi-Center Colonoscopy Quality Measurement Utilizing Natural Language Processing. PMID- 26673515 TI - The use of ultrasound in the assessment of the glenoid labrum of the glenohumeral joint. Part I: Ultrasound anatomy and examination technique. AB - The glenohumeral joint is a spherical articulation with a remarkable range of motion in several planes and decreased stability. The maintenance of joint stability is influenced by the functioning of specific muscle groups in the shoulder region, a complex system of ligaments reinforcing the joint capsule, and the labrum which augments the glenoid fossa. Lesions of the aforementioned structures require accurate diagnosis prior to a decision for operative treatment. Ultrasound is one of the imaging methods that has been widely used in the assessment of various shoulder pathologies. In the author opinion, this imaging modality may also be applied for the evaluation of labral tears. Being attached along the glenoid rim, the labrum forms a collar deepening the glenoid fossa thus increasing area of its contact with the head of the humerus. To better describe the location of lesions, the glenoid labrum is usually divided into certain zones. Most of them may be visualized sonographically. The US examination of the posterior labrum can be performed during evaluation of the infraspinatus and teres minor muscles. The anterior labrum along with capsulolabral complex is seen at the glenoid edge under the subscapularis tendon. Sonographic examination of the inferior labrum is best performed using axillar approach. The superior labrum is only partially available for US examination. A crucial part of the sonographic assessment of the labrum is the dynamic examination during rotation of the upper extremity. The paper presents normal sonographic anatomy of the glenoid labrum and technique of the examination. PMID- 26673516 TI - Galectin-3 Immunohistochemical Expression in Thyroid Neoplasms. AB - BACKGROUND: Galectin-3 has been implicated in the regulation of cellular growth, differentiation and malignant transformation in various organs including thyroid gland. It has been extensively studied as an immunohistochemical (IHC) marker in thyroid malignancy. AIM: To evaluate the diagnostic role of Galectin-3 (Gal-3) in differentiating malignant from benign thyroid neoplasm. MATERIALS AND METHODS: In this observational study we evaluated Gal-3 expression in a spectrum of malignant (30) and benign (20) thyroid neoplasms. The final common diagnosis arrived at after histopathologic evaluation of H&E stained sections by two pathologist's was considered the gold standard. The malignant neoplasms included Papillary Thyroid Carcinoma (PTC), Follicular Thyroid Carcinoma (FTC), Medullary Thyroid Carcinoma (MTC), insular carcinoma, Anaplastic Thyroid Carcinoma (ATC), and metastatic carcinoma. The benign neoplasms included Follicular Adenoma (FA), Hurthle cell adenoma and hyalinizing trabecular adenoma. IHC staining for Gal-3 was performed for all neoplasms with the polymeric method using lyophilized mouse monoclonal antibody. STATISTICAL ANALYSIS: Statistical analysis was done using 2x2 contingency table. Chi-square test with Yates correction was used to calculate p value to ascertain statistical significance. RESULTS: Gal-3 expression was significantly higher in malignant thyroid neoplasms as compared to benign neoplasms (p<0.0001). Gal-3 expression in differentiating malignant from benign neoplasms was found to have sensitivity of 86%, specificity of 85%, positive predictive value of 89.66% and negative predictive value of 80.95%. However, no statistical significance was observed (p=0.4718) when comparing PTC and other malignant lesions in terms of Gal-3 expression. Gal- 3 expression in PTC was found to have sensitivity of 91.3%, specificity of 85%, positive predictive value of 87.5% and negative predictive value of 89.47%. CONCLUSION: Diffuse and strong IHC staining for Gal-3 differentiates malignant from benign tumours. This marker can assist in the diagnosis of thyroid neoplasms with equivocal morphologic features. This study highlights the high sensitivity of Gal-3 for PTC. PMID- 26673517 TI - Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned? AB - BACKGROUND: Intracranial hypertension, defined as an intracranial pressure (ICP) >20 mmHg for a period of more than 5 min, worsens neurologic outcome in traumatic brain injury (TBI). While several mechanisms contribute to poor outcome, impaired cerebral perfusion appears to be a highly significant common denominator. Management guidelines from the Brain Trauma Foundation recommend measuring ICP to guide therapy. In particular, hyperosmolar therapy, which includes mannitol or hypertonic saline (HTS), is frequently administered to reduce ICP. Currently, mannitol (20%) is considered the gold standard hyperosmolar agent. However, HTS is increasingly used in this setting. This review sought to compare the efficacy of mannitol to HTS in severe TBI. METHODS: The PubMed database was used to systematically search for articles comparing mannitol to HTS in severe TBI. The following medical subject headings were used: HTS, sodium lactate, mannitol, ICP, intracranial hypertension, and TBI. We included both prospective and retrospective randomized controlled studies of adult patients with intracranial hypertension as a result of severe TBI who received hyperosmolar therapy. RESULTS: Out of 45 articles, seven articles were included in our review: 5 were prospective, randomized trials; one was a prospective, nonrandomized trial; and one was a retrospective, cohort study. CONCLUSIONS: While all seven studies found that both mannitol and HTS were effective in reducing ICP, there was heterogeneity with regard to which agent was most efficacious. PMID- 26673518 TI - Epidemiology and economics of adult patients hospitalized with urinary tract infections. AB - BACKGROUND: Urinary tract infections (UTI) are among the most common bacterial diseases worldwide, with significant clinical and economic burden. Surveillance of pathogen epidemiology and risk factors for resistant pathogens in the hospital setting may improve the management of UTI. OBJECTIVE: To evaluate microbiology and antimicrobial susceptibility of UTI pathogens, with associated costs, in hospitalized patients. METHODS: Patients diagnosed with UTI between July and September 2013 were retrospectively screened for clinical symptoms and treatment within 24 hours of admission, then categorized into groups: community acquired (Group 1); recent healthcare exposure (Group 2); or a history of identification of an extended-spectrum beta lactamase (ESBL)-producing organism (Group 3). Clinical, epidemiological, and financial data were compared between groups. RESULTS: From 308 included patients, a total of 216 pathogens were identified. Escherichia coli was most commonly identified pathogen, but frequencies differed between groups (p = 0.002), as did those of ESBL-producing pathogens (p < 0.001) and Pseudomonas aeruginosa (p = 0.005). Appropriate empirical therapy also differed between groups (p = 0.003). Length of stay was longer for healthcare associated UTI with inappropriate empirical therapy (5.2 versus 6.3 days, p = 0.016). Increased cost was associated with factors other than antimicrobial costs. Intensive care unit (ICU) stay (p < 0.001), care facility at discharge (p = 0.001), Foley catheter (FC) present on admission (p = 0.002), and Charlson comorbidity index (CCI) (p = 0.017) predicted increased cost overall, while ICU stay (p < 0.001), time to appropriate therapy (p < 0.001), and CCI (p = 0.015) predicted higher cost in patients with pathogens identified. CONCLUSIONS: Changes in antimicrobial susceptibility are evident with exposure to healthcare, the presence of a FC, and a history of resistant pathogens. Risk-based empirical prescribing and rapid de-escalation may improve care and reduce costs. PMID- 26673519 TI - Biological and Molecular Characterization of a Korean Isolate of Cucurbit aphid borne yellows virus Infecting Cucumis Species in Korea. AB - Surveys of yellowing viruses in plastic tunnels and in open field crops of melon (Cucumis melo cultivar catalupo), oriental melon (C. melo cultivar oriental melon), and cucumber (C. sativus) were carried out in two melon-growing areas in 2014, Korea. Severe yellowing symptoms on older leaves of melon and chlorotic spots on younger leaves of melon were observed in the plastic tunnels. The symptoms were widespread and included initial chlorotic lesions followed by yellowing of whole leaves and thickening of older leaves. RT-PCR analysis using total RNA extracted from diseased leaves did not show any synthesized products for four cucurbit-infecting viruses; Beet pseudo-yellows virus, Cucumber mosaic virus, Cucurbit yellows stunting disorder virus, and Melon necrotic spot virus. Virus identification using RT-PCR showed Cucurbit aphid-borne yellows Virus (CABYV) was largely distributed in melon, oriental melon and cucumber. This result was verified by aphid (Aphis gossypii) transmission of CABYV. The complete coat protein (CP) gene amplified from melon was cloned and sequenced. The CP gene nucleotide and the deduced amino acid sequence comparisons as well as phylogenetic tree analysis of CABYV CPs showed that the CABYV isolates were undivided into subgroups. Although the low incidence of CABYV in infections to cucurbit crops in this survey, CABYV may become an important treat for cucurbit crops in many different regions in Korea, suggesting that CABYV should be taken into account in disease control of cucurbit crops in Korea. PMID- 26673521 TI - Usefulness of sonography in the diagnosis of rheumatoid hand. AB - Ultrasound examination is becoming more and more common in patients with rheumatoid diseases. Above all, it enables the assessment of articular soft tissues and constitutes a non-invasive examination. In a rheumatologist's everyday practice, it is conducted at the stage of initial diagnosis as well as to monitor the treatment and to confirm the remission if the clinical picture is ambiguous. The first sign of arthritis (including rheumatoid arthritis) that is visible on ultrasound examination is the thickening of the synovial membrane of the joint cavities, tendon sheaths or bursae. It is frequently accompanied by the exudate in the joint, sheath or bursa. In a subsequent stage, in Doppler examination, enhanced vascularization of the synovial membrane is observed. Sometimes, the inflammatory process of the tendon sheaths also affects the tendons, which might lead to their damage. Moreover, ultrasound examination also reveals erosions and inflammatory cysts (geodes) which attest to the advancement of the disease. A dynamic ultrasound examination enables to diagnose the capsule ligamentous contracture of the interphalangeal joints, which occurs due to the lack of rehabilitation that should begin at the moment of the commencement of the inflammation. The ultrasound image does not allow for the differentiation between various rheumatoid entities, including those encompassing the joints in the hand, wrist. The observed changes, i.e. thickening of the synovial membrane, hyperemia, effusions, erosions or tendon damage, may accompany various rheumatoid entities. The purpose of the ultrasound examination is to recognize these irregularities, determine their localization and advancement and, finally, to monitor the course of treatment. Furthermore, ultrasound scan enables to assess the joints and tendons in a dynamic examination in relation to local ailments of the patient as well as to monitor the biopsy, aspiration and medicine administration. Sonography is used for a US-guided administration of radioisotope substances for synoviorthesis. PMID- 26673522 TI - Fat harvesting site is an important determinant of proliferation and pluripotency of adipose-derived stem cells. AB - To define the optimal fat harvest site and detect any potential differences in adipose-derived stem cells (ASCs) proliferation properties in camels, aspirates from the abdomen and hump sites were compared. Obtained results revealed that ASCs from both abdomen and hump exhibited spindle-shaped and fibroblast-like morphology with hump-derived ASCs being smaller in size and narrower in overall appearance than abdominal ASCs. Abdominal ASCs required a greater time for proliferation than the hump-derived cells. These results were further confirmed with a tetrazolium-based colorimetric assay (MTT) which showed a greater cell proliferation rate for hump ASCs than for the abdomen. Under inductive conditions, ASCs from both abdominal and hump fat deposits maintained their lineage differentiation potential into adipogenic, chondrogenic, and osteogenic lineages during subsequent passages without any qualitative difference. However, expression of alkaline phosphatase was higher in osteogenic differentiated cells from the hump compared with those of the abdomen. Moreover, the increase in calcium content in hump-derived stem cells was higher than that in abdominal derived stem cells. In conclusion, our findings revealed that ASCs can be obtained from different anatomical locations, although ASCs from the hump fat region may be the ideal stem cell sources for use in cell-based therapies. PMID- 26673520 TI - Associations of Abdominal Muscle Area with 4-Year Change in Coronary Artery Calcium Differ by Ethnicity Among Post-Menopausal Women. AB - OBJECTIVE: To examine the association of abdominal muscle area with coronary artery calcium (CAC) presence, extent, and progression in a multi-ethnic cohort of older, community-dwelling post-menopausal women. DESIGN AND SETTING: Cross sectional and longitudinal population-based cohort. PARTICIPANTS: The sample comprised 179 non-Hispanic White women, 116 Filipina women and 144 African American women, all without known CVD, who underwent chest and abdominal computed tomography (CT) scans twice about four years apart for abdominal muscle and fat, as well as CAC. MAIN OUTCOME MEASURES: CAC presence, extent and progression. RESULTS: There was a significant interaction of ethnicity with baseline oblique muscle area (p-for-interaction .01), and marginally significant interactions with baseline total and paraspinal muscle for change in CAC (p-for-interactions both .09). Among Filipina women, each standard deviation (SD) greater total muscle area was associated with a 26% (95% CI (-43%, -4%), P=.02) reduced rate of change in CAC; higher paraspinal and oblique muscle area were associated with a 24% ( 38%, -6%, P=.01) and a 37% (-53%, -16%, P=.0002) reduced rate of change in CAC, respectively. These associations were not significant in African American or non Hispanic White women. There were no significant associations of abdominal muscle with CAC presence or extent, nor were there significant ethnicity by muscle interactions in these models. CONCLUSIONS: Among Filipina women, greater abdominal muscle mass is associated with a decreased rate of CAC progression. Higher muscle mass may be important for this group in reducing CVD outcomes. PMID- 26673523 TI - Evaluating the Influence of the Revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Food Allocation Package on Healthy Food Availability, Accessibility, and Affordability in Texas. AB - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) was implemented to improve the health of pregnant women and children of low socioeconomic status. In 2009, the program was revised to provide a wider variety of healthy food choices (eg, fresh fruits, vegetables, and whole grain items). OBJECTIVES: The purpose of this study was to evaluate (1) the impact of the revised WIC Nutrition Program's food allocation package on the availability, accessibility, and affordability of healthy foods in WIC-authorized grocery stores in Texas; and (2) how the impact of the policy change differed by store types and between rural and urban regions. DESIGN: WIC-approved stores (n=105) across Texas were assessed using a validated instrument (88 items). Pre- (June-September 2009) and post-new WIC package implementation (June-September 2012) audits were conducted. Paired-sample t tests were conducted to compare the differences between pre- and post-implementation audits on shelf width and number of varieties (ie, availability), visibility (ie, accessibility), and inflation adjusted price (ie, affordability). RESULTS: Across the 105 stores, post implementation audits showed increased availability in terms of shelf space for most key healthy food options, including fruit (P<0.001), vegetables (P<0.01), cereal (P<0.001), and varieties of vegetables (P<0.001). Food visibility increased for fresh juices (P<0.001). Visibility of WIC labeling improved for foods such as fruits (P<0.05), WIC cereal (P<0.05), and whole-grain or whole wheat bread (P<0.01). Inflation-adjusted prices decreased only for bread (P<0.001) and dry grain beans (P<0.001). The positive effects of the policy change on food availability and visibility were observed in stores of different types and in different locations, although smaller or fewer effects were noted in small stores and stores in rural regions. CONCLUSIONS: Implementation of the revised WIC food package has generally improved availability and accessibility, but not affordability, of healthy foods in WIC-authorized stores in Texas. Future studies are needed to explore the impact of the revised program on healthy food option purchases and consumption patterns among Texas WIC participants. PMID- 26673524 TI - The usefulness of ultrasound in the diagnostics of Sjogrens's syndrome. PMID- 26673525 TI - Albumin adsorption on CoCrMo alloy surfaces. AB - Proteins can adsorb on the surface of artificial joints immediately after being implanted. Although research studying protein adsorption on medical material surfaces has been carried out, the mechanism of the proteins' adsorption which affects the corrosion behaviour of such materials still lacks in situ observation at the micro level. The adsorption of bovine serum albumin (BSA) on CoCrMo alloy surfaces was studied in situ by AFM and SKPFM as a function of pH and the charge of CoCrMo alloy surfaces. Results showed that when the specimens were uncharged, hydrophobic interaction could govern the process of the adsorption rather than electrostatic interaction, and BSA molecules tended to adsorb on the surfaces forming a monolayer in the side-on model. Results also showed that adsorbed BSA molecules could promote the corrosion process for CoCrMo alloys. When the surface was positively charged, the electrostatic interaction played a leading role in the adsorption process. The maximum adsorption occurred at the isoelectric point (pH 4.7) of BSA. PMID- 26673526 TI - Atomic Bomb Survivors Life-Span Study: Insufficient Statistical Power to Select Radiation Carcinogenesis Model. AB - The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the "neutron discrepancy problem" - the apparent difference between the calculated and measured values of neutron flux in Hiroshima - was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required. PMID- 26673527 TI - Comparative transcriptome analysis of grapevine in response to copper stress. AB - Grapevine is one of the most economically important and widely cultivated fruit crop worldwide. With the industrialization and the popular application of cupric fungicides in grape industry, copper stress and copper pollution are also the factors affecting grape production and berry and wine quality. Here, 3,843 transcripts were significantly differently expressed genes in response to Cu stress by RNA-seq, which included 1,892 up-regulated and 1,951 down-regulated transcripts. During this study we found many known and novel Cu-induced and repressed genes. Biological analysis of grape samples were indicated that exogenous Cu can influence chlorophylls metabolism and photosynthetic activities of grapevine. Most ROS detoxification systems, including antioxidant enzyme, stress-related proteins and secondary metabolites were strongly induced. Concomitantly, abscisic acid functioned as a negative regulator in Cu stress, in opposite action to ethylene, auxin, jasmonic acid, and brassinolide. This study also identified a set of Cu stress specifically activated genes coding copper transporter, P1B-type ATPase, multidrug transporters. Overall, this work was carried out to gain insights into the copper-regulated and stress-responsive mechanisms in grapevine at transcriptome level. This research can also provide some genetic information that can help us in better vinery management and breeding Cu-resistant grape cultivars. PMID- 26673528 TI - CLINICAL PROGNOSTIC FACTORS FOR PATIENTS WITH ANTERIOR KNEE PAIN IN PHYSICAL THERAPY; A SYSTEMATIC REVIEW. AB - BACKGROUND: Although many authors have studied the prognostic factors that may contribute to anterior knee pain, synthesis of the existing evidence has not been performed. PURPOSE: The purpose of this systematic review is to summarize and examine existing prognostic models in patients with anterior knee pain that first present to physical therapists (primary care setting). DESIGN: Systematic review. METHOD: For this review Pubmed, Embase and Cinahl databases were searched and published papers that reported prognostic models for patients with anterior knee pain that first present to physical therapists (primary care setting) were selected. The authors extracted and summarized the univariate and multivariate predictors and evaluated which predictors consistently appeared to be relevant to pain, function, or recovery. RESULTS: Nine studies were included. The quality scores of these studies ranged from 9 to 17 positive items out of 21 items included in the assessment for quality. None of the prognostic models were validated internally or externally. Four studies were considered to be of sufficient quality. The authors of these four studies found 14 different predictors significantly related to pain intensity of which seven with limited evidence. Fifteen different predictors were found that were related to function of which seven with limited evidence. Furthermore, strong evidence was found that baseline pain intensity, pain coping and kinesiophobia are of no predictive value for pain, and activity related pain, pain coping and kinesiophobia are of no predictive value for function at follow up. CONCLUSIONS: Because of the low quality of a number of studies and the heterogeneity of the examined variables and outcome measures of most of the studies, only limited evidence for seven predictors related to pain and seven predictors related to function in patients with anterior knee pain in a primary care setting was found. LEVEL OF EVIDENCE: 1b. PMID- 26673529 TI - A multifunctional ELISA to measure oxidised proteins: oxPin1 in Alzheimer's brain as an example. PMID- 26673530 TI - Exceptional H2 sorption characteristics in a Mg(2+)-based metal-organic framework with small pores: insights from experimental and theoretical studies. AB - Experimental sorption measurements, inelastic neutron scattering (INS), and theoretical studies of H2 sorption were performed in alpha-[Mg3(O2CH)6], a metal organic framework (MOF) that consists of a network of Mg(2+) ions coordinated to formate ligands. The experimental H2 uptake at 77 K and 1.0 atm was observed to be 0.96 wt%, which is quite impressive for a Mg(2+)-based MOF that has a BET surface area of only 150 m(2) g(-1). Due to the presence of small pore sizes in the MOF, the isosteric heat of adsorption (Qst) value was observed to be reasonably high for a material with no open-metal sites (ca. 7.0 kJ mol(-1)). The INS spectra for H2 in alpha-[Mg3(O2CH)6] is very unusual for a porous material, as there exist several different peaks that occur below 10 meV. Simulations of H2 sorption in alpha-[Mg3(O2CH)6] revealed that the H2 molecules sorbed at three principal locations within the small pores of the framework. It was discovered through the simulations and two-dimensional quantum rotation calculations that different groups of peaks correspond to particular sorption sites in the material. However, for H2 sorbed at a specific site, it was observed that differences in the positions and angular orientations led to distinctions in the rotational tunnelling transitions; this led to a total of eight identified sites. An extremely high rotational barrier was calculated for H2 sorbed at the most favorable site in alpha-[Mg3(O2CH)6] (81.59 meV); this value is in close agreement to that determined using an empirical phenomenological model (75.71 meV). This rotational barrier for H2 exceeds those for various MOFs that contain open-metal sites and is currently the highest yet for a neutral MOF. This study highlights the synergy between experiment and theory to extract useful and important atomic level details on the remarkable sorption mechanism for H2 in a MOF with small pore sizes. PMID- 26673531 TI - Neuroprotective Effect of Lercanidipine- A Novel Calcium Channel Blocker in Albino Mice. AB - BACKGROUND: The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. OBJECTIVE: (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. MATERIALS AND METHODS: Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc 'Dunnett t-test'. RESULTS: Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension. Combination of lercanidipine (3 mg/kg) and phenytoin had offered 100% protection. The results also revealed that the test drug didn't impair the motor coordination and locomotor activity in mice. CONCLUSION: The present study had demonstrated that lercanidipine could be potential novel candidate for the treatment of convulsions. PMID- 26673532 TI - Stereoselective Alkylation of the Vinylketene Silyl N,O-Acetal and Its Application to the Synthesis of Mycocerosic Acid. AB - Stereoselective alkylation of the vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using activated alkyl halides including allyl iodides, benzyl iodides, and propargyl iodide with Ag(I) ion in the presence of BF3.OEt2. The reaction proceeded to give reduced polyketides in high stereoselectivity. The synthesis of mycocerosic acid, a component of the cell envelope of Mycobacterium tuberculosis, has been accomplished by this methodology. During the synthetic studies, 2-methylbenzimidazole was found to be a bulky proton source which worked in the presence of liquid ammonia. PMID- 26673533 TI - Manual Ambidexterity Predicts Robotic Surgical Proficiency. AB - BACKGROUND: The manual dexterity of a surgeon is known to be related with surgical proficiency. Recently, as an objective measurement of surgical skills, inanimate methods using several types of simulators have been introduced. Using these simulators, we aimed to investigate the impact of manual dexterity on laparoscopic and robotic surgical proficiency. MATERIALS AND METHODS: Fellow surgeons, surgical residents, and medical students (n = 32) participated in this study. For the measurement of dexterity, the sums and differences of the right and left hand performance times for the Grooved Pegboard Test were used as an index of dexterity speed and ambidexterity, respectively. The performance times during three sessions of laparoscopic suturing using a D-box trainer and the performance scores during three sessions using two robotic suturing programs with different degrees of difficulty provided by the da Vinci(r) Skills SimulatorTM (Intuitive Surgical Inc., Sunnyvale, CA) were analyzed according to the measured manual dexterity. RESULTS: Manual dexterity was not a significant factor for performance time during laparoscopic suturing, which was more influenced by participants' surgical experiences. In robotic suturing, the performance score was impacted significantly by manual dexterity in terms of ambidexterity rather than dexterity speed. For an easy robotic suturing task, the gap of proficiency between the lower and higher ambidexterity groups was decreased successively with each of the three sessions. However, that gap in cases with a difficult task was maintained consistently throughout all three sessions. CONCLUSIONS: The degree of ambidexterity was an initial predictor for proficiency with simulated robotic suture. However, this relation could be lessened through a few sessions of training, although for a more difficult task further repetitions would be needed. PMID- 26673534 TI - Three-Dimensional Versus Two-Dimensional Imaging in Adult Versus Pediatric Laparoscopy: A Simulator Box Study. AB - AIM: Three-dimensional (3D) imaging has been shown to enhance depth perception and facilitate operations in training box studies and in adult laparoscopy. However, there are no data on 3D vision in small working spaces, which are common pediatric surgery. Therefore, this study examined the impact of monoscopic versus stereoscopic visualization in large versus small working spaces in individuals with varying surgical expertise. MATERIALS AND METHODS: Twenty-four individuals with varying surgical expertise (experts, surgical residents, and surgical novices) were involved in the study. Participants were asked to perform four tasks in large (24- * 30- * 50-cm) and small (9- * 11- * 18-cm) training boxes, using two-dimensional and 3D imaging. Sixteen standardized procedures were performed by each participant. Primary outcome measure was performance time. Secondary outcome parameters included the number of errors and subjective depth perception. RESULTS: Surgical novices showed a shorter performance time and lesser total number of errors in large and small training boxes using 3D imaging. Residents achieved a significantly shorter performance time in the large and lesser number of errors in the small box. With 3D vision experts performed laparoscopic suturing in the small box and target touching in both boxes significantly faster. The overall performance time and total number of errors of experts were not different in the two boxes. Subjective depth perception with 3D vision in the small box in all groups and in the small box in surgical novices was significantly better. CONCLUSIONS: We identified several advantages of 3D vision in individuals with varying surgical expertise. However, the benefits were rather experienced by surgical novices and residents than by experts. Differences in performance time and number of errors were similar in the large and small simulator boxes. PMID- 26673535 TI - Relationship Between Dental Fluorosis and Intelligence Quotient of School Going Children In and Around Lucknow District: A Cross-Sectional Study. AB - BACKGROUND: Fluoridation of drinking water, despite being regarded as one of the top ten public health achievements of the twentieth century, has remained a much debated concept. Various studies on animals and aborted human fetuses have confirmed that excessive fluoride intake during infancy and early childhood, causes a number of irreversible structural and functional changes in the CNS leading to memory, learning and intellectual deficits. AIM: To compare the IQ levels of school children of two different locations, having different fluoride levels in water, and to establish a relationship between fluoride levels, prevalence of fluorosis and its effect on IQ levels. MATERIALS AND METHODS: A cross-sectional study was conducted among 429 children aged 6 - 12 years, selected by stratified random sampling from two different areas with different levels of fluoride in drinking water in and around Lucknow district. Dental fluorosis was measured using Dean's Fluorosis Index. Intelligence Quotient was measured using Raven's Coloured Progressive Matrices (1998 edition). RESULTS: Majority of the fluorosis free children (76.3%) had an IQ grade 2 (definitely above the average). Majority of the children suffering from very mild and mild dental fluorosis were found to have IQ grade 3 (Intellectually average). Children with moderate cases of dental fluorosis were found to have IQ grade 4 (Definitely below average). Only 5 children with severe fluorosis were included in the study and they all were found to have an IQ grade 5. Hence, a trend of increase in the IQ grade (decrease in intellectual capacity) was observed indicating a strong correlation between fluorosis grade and IQ grade. CONCLUSION: Findings of this study suggest that the overall IQ of the children exposed to high fluoride levels in drinking water and hence suffering from dental fluorosis were significantly lower than those of the low fluoride area. PMID- 26673538 TI - Development and evaluation of a novel product to remove surface contamination of hazardous drugs. AB - Background Even while following best practices, surface exposures of hazardous drugs (HDs) are high and numerous. Thus, it is important to develop new products to reduce the surface contamination of HDs. Hazardous Drug Clean (HDCleanTM) was developed to decontaminate and remove HDs from various types of surfaces and overcome the problems associated with other cleaning products. Methods HDClean was evaluated to remove mock surface exposures of HDs (docetaxel, paclitaxel, ifosfamide, cyclophosphamide, 5-FU, and cisplatin) from various types of surfaces. In two separate cancer centers, studies were performed to evaluate HDClean in reducing surface contamination of HDs in the pharmacy departments where no closed system transfer device (CSTD) was used. In a third cancer center, studies were performed comparing the effectiveness of a CSTD + Surface Safe compared with CSTD + HDClean to remove HDs. Results HDClean was able to completely remove mock exposures of a wide range of HDs from various surfaces (4 and 8 sq ft areas). Daily use of HDClean was equal to or more effective in reducing surface contamination of HDs in two pharmacies compared with a CSTD. HDClean was significantly more effective in removing HDs, especially cisplatin, compared with Surface Safe and does not have the problems associated with decontamination solutions that contain sodium hypochlorite. Conclusion These studies support HDClean as an effective decontaminating product, that HDClean is more effective than Surface Safe in removing HDs and is equal to or more effective than CSTD in controlling HD surface exposures. PMID- 26673539 TI - Morphometric Analysis of Sub-axial Cervical Vertebrae and Its Surgical Implications. AB - BACKGROUND: The predilection of the cervical spine to a wide array of traumatic, degenerative and neoplastic diseases necessitates frequent surgical interventions. For successful surgical management of these conditions, a detailed anatomical knowledge of the cervical spine is required but variability in vertebral dimensions exists amongst different races and prevents the standardization of measurements. AIM: The aim of this study was to present a morphometric reference database for cervical vertebrae of the Indian population and enable comparisons with other populations. MATERIALS AND METHODS: The study was conducted on 203 typical (C3-C6) cervical vertebrae. Linear measurements of the vertebrae were taken with the help of digital Vernier caliper and angular measurements were determined with software Image J. STATISTICAL ANALYSIS: Mean and standard deviation of the morphometric parameters taken into account were analysed. The comparison of morphometric dimensions of the right and left sides was performed using Student's t-test and p-value was calculated. RESULTS: The morphometric analysis of the cervical vertebrae demonstrated that when compared with other races, the mean height (11.39 +/- 1.08 mm) and transverse diameters (22.18 +/- 2.52 mm) of the vertebral body were larger but antero-posterior diameter was less, making the vertebral bodies in Indians transversely longer. The dimensions of the pedicle, laminae, articular processes and spinous process were smaller when compared to other populations. There existed a highly significant difference (p=0.002) between the widths of the right and left superior & inferior articular processes. A great disparity of the pedicle transverse angle was noted in different populations but in Indians the angle was 44.47 +/- 2.81. CONCLUSION: The present morphometric study in Indian population would be valuable for the successful instrumentation of the cervical spine as smaller dimensions of the cervical vertebrae pose a challenge to the surgeons during application of plates and screws. The data would be helpful in designing spinal implants and permit identification of osteological remains. PMID- 26673540 TI - Letter: Anatomy and Auditory Brainstem Implants. PMID- 26673541 TI - Incidence and Prevalence of Musculoskeletal Injury in Ballet: A Systematic Review. AB - BACKGROUND: Most published studies on injuries in the ballet dancer focus on the lower extremity. The rigors of this activity require special training and care. By understanding prevalence and injury pattern to the musculoskeletal system, targeted prevention and treatment for this population can be developed. PURPOSE: To determine the incidence and prevalence of musculoskeletal injuries in ballet. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review registered with PROSPERO was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Level 1 through 4 evidence studies reporting incidence of musculoskeletal injuries in male and female ballet dancers were included, with the numbers and types of injuries extracted from each. Injury rates were recorded and calculated based on professional status, sex, and nature of injury. Incidence was defined as number of injuries sustained over a specific time. Prevalence was defined as proportion of subjects with an injury at a given point in time. RESULTS: The studies analyzed reported injury incidence or prevalence in more than 1365 amateur and 900 professional dancers. The mean age was 16.2 years among amateur and 27.0 years among professional dancers. The incidence of injury among amateur dancers was 0.99 and 1.09 injuries per 1000 dance hours in males and females, respectively; 75% of injuries were overuse, with similar rates among males and females. In professional dancers, the incidence of injury was 1.06 and 1.46 injuries per 1000 dance hours in males and females, respectively, and 64% of female injuries were overuse, compared with 50% in males (P < .001). Only 3 studies provided prevalence data, including 62% prevalence of lumbosacral pain, 58% painful snapping hip, and 29% patellofemoral pain. Lower extremity injuries comprised 66% to 91% of all injuries, with the foot and ankle accounting for 14% to 57%. CONCLUSION: The overall incidence of injury among amateur and professional ballet dancers is 0.97 and 1.24 injuries per 1000 dance hours, respectively. The majority are overuse in both amateur and professional dancers, with amateur ballet dancers showing a higher proportion of overuse injuries than professionals (P < .001). Male professional dancers show a higher proportion of traumatic injuries, accounting for half of their injuries (P < .001). PMID- 26673542 TI - Pharmacological inhibition of eicosanoids and platelet-activating factor signaling impairs zymosan-induced release of IL-23 by dendritic cells. AB - The engagement of the receptors for fungal patterns induces the expression of cytokines, the release of arachidonic acid, and the production of PGE2 in human dendritic cells (DC), but few data are available about other lipid mediators that may modulate DC function. The combined antagonism of leukotriene (LT) B4, cysteinyl-LT, and platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero 3-phosphocholine) inhibited IL23A mRNA expression in response to the fungal surrogate zymosan and to a lower extent TNFA (tumor necrosis factor-alpha) and CSF2 (granulocyte macrophage colony-stimulating factor) mRNA. The combination of lipid mediators and the lipid extract of zymosan-conditioned medium increased the induction of IL23A by LPS (bacterial lipopolysaccharide), thus suggesting that unlike LPS, zymosan elicits the production of mediators at a concentration enough for optimal response. Zymosan induced the release of LTB4, LTE4, 12 hydroxyeicosatetraenoic acid (12-HETE), and PAF C16:0. DC showed a high expression and detectable Ser663 phosphorylation of 5-lipoxygenase in response to zymosan, and a high expression and activity of LPCAT1/2 (lysophosphatidylcholine acyltransferase 1 and 2), the enzymes that incorporate acetate from acetyl-CoA into choline-containing lysophospholipids to produce PAF. Pharmacological modulation of the arachidonic acid cascade and the PAF receptor inhibited the binding of P-71Thr-ATF2 (activating transcription factor 2) to the IL23A promoter, thus mirroring their effects on the expression of IL23A mRNA and IL-23 protein. These results indicate that LTB4, cysteinyl-LT, and PAF, acting through their cognate G protein-coupled receptors, contribute to the phosphorylation of ATF2 and play a central role in IL23A promoter trans-activation and the cytokine signature induced by fungal patterns. PMID- 26673543 TI - The peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents NF-kappaB activation in cisplatin nephrotoxicity through the reduction of p65 acetylation via the AMPK-SIRT1/p300 pathway. AB - The thiazolidinedione pioglitazone, which is also a PPAR-gamma agonist, now is widely used in patients with hypercholesterolemia and hypertriglyceridemia. NF kappaB is a ubiquitously expressed transcription factor controlling the expression of numerous genes involved in inflammation. The aim of the present study was to evaluate whether the activation of PPAR-gamma attenuates the cisplatin-induced NF-kappaB activation in cisplatin nephrotoxicity. The results showed that the PPAR-gamma agonist pioglitazone decreased the expression of NF kappaB p65 transcription target genes (e.g., IL-6, IL-1beta, and TNF-alpha) and inhibited histological injury and inflammatory cells infiltration in cisplatin nephrotoxicity. The suppression of NF-kappaB activity following pioglitazone treatment inhibited the cisplatin-induced IkappaB-alpha degredation and NF-kappaB p65 subunit translocation. Translocation of the NF-kappaB p65 subunit depends on p65 acetylation, which primarily regulated by SIRT1 or p300. Notably, AMP kinase (AMPK) activation not only decreased the phosphorylation, activation and p65 interaction of p300 but also increased SIRT1 expression, activation and p65 binding, thus leading to a significant reduction in p65 acetylation. Interestingly, the reduction of IL-6, TNF-alpha and IL-1beta, the inhibition of histological injury and the inflammatory cells infiltration following pioglitazone treatment in cisplatin nephrotoxicity were attenuated after treatment with the PPAR-gamma antagonist GW9662. These results suggest that the PPAR-gamma agonist pioglitazone prevents NF-kappaB activation in cisplatin nephrotoxicity through a reduction in p65 acetylation via the AMPK-SIRT1/p300 pathway. PMID- 26673544 TI - An in vitro examination of selenium-cadmium antagonism using primary cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes. AB - The present study evaluated the ameliorative properties of selenium (Se) against cadmium (Cd)-induced oxidative stress, using isolated rainbow trout (Oncorhynchus mykiss) hepatocytes in primary culture as the model experimental system. Cadmium (Cd) is known to induce cytotoxic effects by disrupting cellular oxidative homeostasis. On the other hand, selenium (Se) is an essential component of biological antioxidative machinery, and thus may provide protection against the toxic insults of Cd by augmenting the cellular antioxidant response. However, Se, when present above the threshold concentration, can also induce reactive oxygen species (ROS) generation and cause oxidative damage. In this experiment, trout hepatocytes in primary culture were exposed to 100 uM Cd, alone or in combination with different concentrations (25-500 uM) of selenite (SeO3(2-)) or selenomethionine (SeMet) for 48 h. Our findings indicated that both chemical forms of Se, at the lowest concentration used (25 uM), significantly reduced Cd induced cytotoxicity (measured as cell viability). In contrast, Se at higher concentrations (>= 50 uM) did not offer any protection against a Cd induced decrease in cell viability. The reduced cytotoxicity of Cd in the presence of 25 uM selenite or SeMet was associated with reduced intracellular ROS production, recovery of the cellular thiol status (ratio of reduced and oxidized glutathione), and amelioration in the activities of major enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). Co-treatment of hepatocytes with Cd and pharmacological antioxidants (TEMPO and NAC) also reduced Cd-induced oxidative stress in trout hepatocytes. This provided further evidence that Se likely ameliorates Cd toxicity via different antioxidative mechanisms. PMID- 26673545 TI - A highly-efficient blue-light excitable red phosphor: intramolecular pi-stacking interactions in one dinuclear europium(iii) complex. AB - A series of ternary dinuclear europium(iii) complexes [Eu2(2,7-BTFDBC)3 n(DBM)2n(Phen)2] (n = 0, 1, or 2) were synthesized by using 2,7-bis(4'4'4' trifluoro-1,3-dioxobutyl)-(9-ethyl-9H-carbazole) (2,7-BTFDBC), dibenzoylmethane (DBM), 1,10-phenanthroline (Phen) and europium(iii) ions. All these complexes display a broad excitation band in the blue region and high intensity emission with high colour purity. The intensity of emission significantly increases with the increase of DBM in [Eu2(2,7-BTFDBC)3-n(DBM)2n(Phen)2] (n = 0, 1, or 2). The theoretical predictions of the molecular geometry and electronic absorption spectrum of [Eu2(2,7-BTFDBC)(DBM)4(Phen)2] confirm that the pendant phenyl domains engage in multiple T-shaped and parallel-displaced pi-stacking interactions with the coordination sphere of two europium(iii) centers. Using [Eu2(2,7-BTFDBC)(DBM)4(Phen)2] as a red phosphor, a single red LED has been obtained with a ~460 nm-emitting GaN chip. PMID- 26673546 TI - Interconnected Porous Polymers with Tunable Pore Throat Size Prepared via Pickering High Internal Phase Emulsions. AB - Interconnected macroporous polymers were prepared by copolymerizing methyl acrylate (MA) via Pickering high internal phase emulsion (HIPE) templates with modified silica particles. The pore structure of the obtained polymer foams was observed by field-emission scanning electron microscopy (FE-SEM). Gas permeability was characterized to evaluate the interconnectivity of macroporous polymers. The polymerization shrinkage of continuous phase tends to form open pores while the solid particles surrounding the droplets act as barriers to produce closed pores. These two conflicting factors are crucial in determining the interconnectivity of macroporous polymers. Thus, poly-Pickering HIPEs with high permeability and well-defined pore structure can be achieved by tuning the MA content, the internal phase fraction, and the content of modified silica particles. PMID- 26673547 TI - Erratum: A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1. AB - [This corrects the article DOI: 10.7555/JBR.29.20150034.]. PMID- 26673548 TI - Critical field enhancement of asymptotic optical bound states in the continuum. AB - We study spectral singularities and critical field enhancement factors associated with embedded photonic bound states in subwavelength periodic Si films. Ultrahigh Q resonances supporting field enhancement factor exceeding 10(8) are obtained in the spectral vicinity of exact embedded eigenvalues in spite of deep surface modulation and vertical asymmetry of the given structure. Treating relations between the partial resonance Q and field enhancement factors with an analytical coupled-mode model, we derive a general strategy to maximize the field enhancement associated with these photonic bound states in the presence of material dissipation. The analytical expression for the field enhancement quantitatively agrees with rigorous numerical calculations. Therefore, our results provide a general knowledge for designing practical resonance elements based on optical bound states in the continuum in various applications. PMID- 26673549 TI - Burnout in medical residents. PMID- 26673550 TI - Heart failure and new perspectives for internists. PMID- 26673551 TI - Skeletal muscle mass is associated with severe dysphagia in cancer patients. AB - BACKGROUND: The purpose of this study was to assess the association between skeletal muscle mass, activities of daily living (ADLs) and severe dysphagia in cancer patients. METHODS: A nested case-control study was performed in 111 consecutive cancer patients with dysphagia who were prescribed speech therapy. Skeletal muscle mass comprising the cross-sectional area of the left and right psoas muscles was assessed via abdominal computed tomography at the third lumbar vertebral level. ADLs were evaluated by the Barthel Index. The severity of dysphagia was assessed by the Food Intake Level Scale and was characterized by non-oral feeding or oral food intake at discharge. Univariate and logistic regression analyses were applied to examine the associations between dysphagia, skeletal muscle index (SMI) and ADLs. RESULTS: There were 86 men and 25 women (mean age, 70 years). The mean SMI was 5.68 +/- 1.74 cm(2)/m(2) in men and 4.43 +/- 1.21 cm(2)/m(2) in women. The median Barthel Index score was 20. Thirty-three patients were on non-oral feeding at discharge. The mean SMI did not differ significantly between non-oral feeding and oral food intake groups in t-test. The median Barthel Index score was lower in the non-oral feeding group in Mann Whitney U test. Logistic regression analysis of the severity of dysphagia adjusted for age, sex, SMI, Barthel Index score, serum albumin, cancer type and stage, and vocal cord paralysis showed that SMI was associated independently with oral food intake at discharge. Barthel Index score showed a tendency to be associated with oral food intake. CONCLUSIONS: Skeletal muscle mass is associated with severe dysphagia in cancer patients. ADLs show a tendency to be associated with severe dysphagia in cancer patients. PMID- 26673552 TI - Organometallic chemistry meets crystal engineering to give responsive crystalline materials. AB - Dynamically porous crystalline materials have been obtained by engineering organometallic molecules. This feature article deals with organometallic wheel and-axle compounds, molecules with two relatively bulky groups (wheels) connected by a linear spacer. The wheels are represented by half-sandwich Ru(ii) moieties, while the spacer can be covalent or supramolecular in character. Covalent spacers are obtained using divergent bidentate ligands connecting two [(arene)RuX2] groups. Supramolecular spacers are instead obtained by exploiting the dimerization of COOH or C(O)NH2 groups appended to N-based ligands. A careful choice of ligand functional groups and X ligands leads to the isolation of crystalline materials with remarkable host-guest properties, evidenced by the possibility of reversibly capturing/releasing volatile guests through heterogenous solid-gas reactions. Structural correlations between the crystalline arrangement of the apohost and the host-guest compounds allow us to envisage the structural path followed by the system during the exchange processes. PMID- 26673553 TI - Transforming Growth Factor Beta 1 Modulates the Functional Expression of the Neurokinin-1 Receptor in Human Keratocytes. AB - PURPOSE: Transforming growth factor beta 1 (TGF-beta1) is a cytokine involved in a variety of processes, such as differentiation of fibroblasts into myofibroblasts. TGF-beta1 has also been shown to delay the internalization of the neurokinin-1 receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a truncated form, triggering different cellular responses. SP has been shown to affect important events in the cornea - such as stimulating epithelial cell proliferation - processes that are involved in corneal wound healing and thus in maintaining the transparency of the corneal stroma. An impaired signaling through NK-1 R could thus impact the visual quality. We hypothesize that TGF-beta1 modulates the expression pattern of NK-1 R in human corneal stroma cells, keratocytes. The purpose of this study was to test that hypothesis. METHODS: Cultures of primary keratocytes were set up with cells derived from healthy human corneas, obtained from donated transplantation graft leftovers, and characterized by immunocytochemistry and Western blot. Immunocytochemistry for TGF-beta receptors and NK-1 R was performed. Gene expression was assessed with real-time polymerase chain reaction (qPCR). RESULTS: Expression of TGF-beta receptors was confirmed in keratocytes in vitro. Treating the cells with TGF-beta1 significantly reduced the gene expression of NK-1 R. Furthermore, immunocytochemistry for NK-1 R demonstrated that it is specifically the expression of the full-length isotype of the receptor that is reduced after treatment with TGF-beta1, which was also confirmed with qPCR using a specific probe for the full-length receptor. CONCLUSIONS: TGF-beta1 down-regulates the gene expression of the full-length variant of NK-1 R in human keratocytes, which might impact its signaling pathway and thus explain the known delay in internalization after activation by SP seen with TGF-beta1 treatment. PMID- 26673554 TI - Regular consumption of black tea increases circulating kynurenine concentrations: A randomized controlled trial. AB - BACKGROUND: Circulating neopterin and the ratio of kynurenine to tryptophan (KYN/TRP) concentrations are biomarkers of immune activation that have been linked to cardiovascular and total mortality. Several in vitro studies indicated that tea flavonoids and other antioxidants can modulate tryptophan breakdown rates and neopterin production in immune cells. We aimed to assess the effects of regular black tea consumption on tryptophan and neopterin metabolisms in vivo. METHODS: Participants were healthy individuals, with no major illnesses and having normal to mildly elevated systolic blood pressure. They were randomly assigned to consume 3 cups/day of either powdered black tea solids (tea; n = 45) or a flavonoid-free caffeine-matched beverage (control; n = 49). Serum concentrations of tryptophan, kynurenine and neopterin were assessed at baseline and again at 3 and 6 months after daily ingestion of the respective beverage. RESULTS: Regular consumption of tea over 6 months, compared to control, did not significantly alter neopterin (p = 0.13) or tryptophan (p = 0.85) concentrations, but did result in significantly higher kynurenine (p = 0.016) and KYN/TRP (p = 0.012). Relative to the control group, in the tea group kynurenine and KYN/TRP increased during the treatment period by 0.28 MUmol/L (95% CI: - 0.04, 0.60) and 3.2 MUmol/mmol (95% CI: - 1.6, 8.0), respectively at 3 months, and by 0.48 MUmol/L (95% CI: 0.16, 0.80) and 7.5 MUmol/mmol (95% CI: 2.5, 12.5), respectively at 6 months. CONCLUSIONS: Increased circulation of kynurenine and KYN/TRP following regular black tea consumption may indicate enhanced tryptophan breakdown, possibly due to immune activation-induced tryptophan degrading enzyme indoleamine 2,3-dioxygenase. GENERAL SIGNIFICANCE: The influence of black tea consumption on biomarkers of immune system activation could relate to its general health benefits. Data suggests that the net effect strongly depends on the individual immune state, being stimulatory in healthy individuals, while acting more immune dampening in situations with an inflammatory background. PMID- 26673555 TI - Role of leukotrienes in diabetic retinopathy. AB - The pathophysiology of diabetic retinopathy is highly complex and encompasses the detrimental roles of numerous factors/mediators in inducing various molecular pathological alterations. Although the roles of many inflammatory mediators, involved in the progression of this complication, have been thoroughly researched and studied, the part played by leukotrienes remains widely neglected. This review focuses on leukotrienes-induced mediation and aggravation of the pathological pathways, such as inflammation, oxidative stress and retinal angiogenesis, responsible for exhibition of various characteristic events including leukostasis, macular edema, retinal neovascularization and vitreous hemorrhages, hence, marking the advent of diabetic retinopathy. Acknowledging these roles, it might be possible to potentially utilize leukotrienes antagonists for suppressing or reducing the intensity of the mentioned pathological alterations. Hence, leukotrienes antagonists may act as an effective adjuvant therapy either along with other developing novel therapies (such as anti-VEGF or anti-TNF-alpha therapy), or with the established conventional laser photocoagulation treatment, to provide additional symptomatic relief or, possibly prevent the progression of diabetic retinopathy. PMID- 26673556 TI - Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules. AB - Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications may exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile. Most of these CORMs exhibited bactericidal properties that decrease in the following order: CORM-2 > CORM-3 > ALF062 > ALF850 > ALF186 > ALF153 > [Fe(SBPy3)(CO)](BF4)2. A similar yet not entirely coincident decreasing order was found for their induction of intracellular reactive oxygen species (ROS) in E. coli. In contrast, studies in model animal cells showed that for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria. Importantly, these CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney LLC-PK1 epithelial cells, and liver cell line HepG2. CORM-2 and CORM-3 delivered CO to the intracellular space of both E. coli and the two types of tested eukaryotic cells, yet toxicity was only elicited in the case of E. coli. CO delivered by ALF186 into the intercellular space did not enter E. coli cells and the compound was not toxic to either bacteria or to eukaryotic cells. The Fe(ii) carbonyl complex [Fe(SBPy3)(CO)](2+) had the reverse, undesirable toxicity profile, being unexpectedly toxic to eukaryotic cells and non-toxic to E. coli. ALF153, the most stable complex in the whole set, was essentially devoid of toxicity or ROS induction ability in all cells. These results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they can show opposite toxicity profiles towards bacteria and eukaryotic cells; (ii) their activity can be modulated through manipulation of the ancillary ligands, as shown with the three {Ru(CO)3}(2+) and two zerovalent Mo based CORMs; and (iii) their toxicity to eukaryotic cells can be made acceptably low. With this new approach, this work contributes to the understanding of the roots of the bactericidal action of CORMs and helps in establishing strategies for their development into a new class of antibiotics. PMID- 26673557 TI - Annular pancreas in Trichorhinophalangeal syndrome type II with 8q23.3-q24.12 interstitial deletion. AB - BACKGROUND: Trichorhinophalangeal syndrome type II (TRPS II, OMIM # 150230) is a rare autosomal dominant genetic disorder characterized by craniofacial and skeletal abnormalities. Loss of functional copies of the TRPS1 gene at 8q23.3 and the EXT1 gene at 8q24.11 are considered to be responsible for the syndrome. CASE PRESENTATION: Herewith, we report an 8-year-old girl with sparse scalp hair, bulbous nose, thin upper lip, broad eyebrows, phalangeal abnormalities of both hands/toes, multiple exostoses, mild intellectual impairment and severe malnutrition. In addition, the patient also had annular pancreas, a rare co existing feature in patients with TRPS II. CONCLUSIONS: A contiguous 5.47 Mb deletion involving 8q23.3-q24.12 was detected by array comparative genomic hybridization (aCGH), leading to haploinsufficiency of 10 protein coding genes, 1 long non-coding RNA and 1 microRNA. Quantitative PCR (qPCR) examination confirmed half-reduced DNA copy of the patient and normal expression of both parents, indicating a de novo origin of the deletion and complete penetrance of the mutation. PMID- 26673558 TI - Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. PMID- 26673559 TI - Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease. AB - BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 +/- 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress. PMID- 26673560 TI - Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation. AB - BACKGROUND: Patients with atrial fibrillation (AF) often take multiple medications. METHODS AND RESULTS: We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on >= 10. Although polypharmacy was not associated with higher risk of stroke or non-central nervous system embolism (adjusted hazard ratio, 1.02 for >= 10 versus 0-4 medications; 95% confidence interval, 0.76-1.38), it was associated with higher risks of the combined end point of stroke, non-central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for >= 10 versus 0-4 medications; 95% confidence interval, 1.18-1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for >= 10 versus 0-4 medications; 95% confidence interval, 1.31-1.65). There was no significant difference in primary efficacy (adjusted interaction P=0.99) or safety outcomes (adjusted interaction P=0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52-0.95; interaction P=0.0074). There was no evidence of differential outcomes in those treated with >= 1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. CONCLUSIONS: In a population of patients with atrial fibrillation, two thirds were on >= 5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID- 26673561 TI - Serotonin-secreting enteroendocrine cells respond via diverse mechanisms to acute and chronic changes in glucose availability. AB - BACKGROUND: Enteroendocrine cells collectively constitute our largest endocrine tissue, with serotonin (5-HT) secreting enterochromaffin (EC) cells being the largest component (~50 %). This gut-derived 5-HT has multiple paracrine and endocrine roles. EC cells are thought to act as nutrient sensors and luminal glucose is the major absorbed form of carbohydrate in the gut and activates secretion in an array of cell types. It is unknown whether EC cells release 5-HT in response to glucose in primary EC cells. Furthermore, fasting augments 5-HT synthesis and release into the circulation. However, which nutrients cause fasting-induced synthesis of EC cell 5-HT is unknown. Here we examine the effects of acute and chronic changes in glucose availability on 5-HT release from intact tissue and single EC cells. METHODS: We utilised established approaches in our laboratories measuring 5-HT release in intact mouse colon with amperometry. We then examined single EC cells function using our published protocol in guinea-pig colon. Single cell Ca(2+) imaging and amperometry were used with these cells. Real-time PCR was used along with amperometry, on primary EC cells cultured for 24 h in 5 or 25 mM glucose. RESULTS: We demonstrate that acute increases in glucose, at levels found in the gut lumen rather than in plasma, trigger 5-HT release from intact colon, and cause Ca(2+) entry and 5-HT release in primary EC cells. Single cell amperometry demonstrates that high glucose increases the amount of 5-HT released from individual vesicles as they undergo exocytosis. Finally, 24 h incubation of EC cells in low glucose causes an increase in the transcription of the 5-HT synthesising enzyme Tph1 as well as increasing in 5-HT secretion in EC cells. CONCLUSIONS: We demonstrate that primary EC cells respond to acute changes in glucose availability through increases in intracellular Ca(2+) the activation of 5-HT secretion, but respond to chronic changes in glucose levels through the transcriptional regulation of Tph1 to alter 5-HT synthesis. PMID- 26673562 TI - Intestinal Parasitoses in HIV Infected Children in a Nigerian Tertiary Hospital. AB - BACKGROUND: Intestinal parasitoses are common amongst people living in developing countries. They may impact negatively on the growth and health of immune competent children. There is paucity of information on the association between HIV and intestinal parasitoses in African children. OBJECTIVE: To identify the intestinal infections responsible for infections in HIV infected children and document characteristics of HIV infected children at a Nigerian teaching hospital. MATERIALS AND METHODS: Consecutive children attending a Paediatric anti retroviral clinic were studied. Information such as socio-demographics and clinical characteristics elicited from clinical examination were recorded in the proforma. Stool samples of the children were obtained and examined for intestinal parasites. Data was analysed with the SPSS 18 software. RESULTS: A total 52 children were studied and their age ranged between 6 months and 14 years, with a mean of 6.5 years +/- 3.93. The 52 were made up of 27 boys and 25 girls, giving a male: female ratio of 1.1:1. 10 (19.2%) of the 52 children were infected with cryptosporidium spp, while 1(1.9%) had Ascaris lumbricoides infestation. Anti helminthics had previously been administered to 86.5% of children studied. Those who previously received anti-helminthics had lower prevalence estimates of cryptosporidium infections. (p<0.01, RR = 0.42, 95%CI = 0.20 - 0.90). Children on co-trimoxazole prophylaxis had lower prevalence estimates of cryptosporidium infections. (P<0.01, RR = 0.35, 95%CI = 0.14 - 0.91). Use of highly active antiretroviral drugs was also associated with lower prevalence estimates of intestinal cryptosporidium. (p=0.04, RR = 0.58, 95%CI = 0.31 - 1.10). Eight of the 10 children infected with cryptosporidium had recurrent abdominal pain in comparison with the six with recurrent abdominal pain amongst the 42 without cryptosporidial infections. (p<0.01, RR=5.6, 95%CI= 2.51 - 12.1). CONCLUSION: Cryptosporidial infection is the most common intestinal parasitoses among HIV infected children in this study, while intestinal helminthiasis are not so common. Anti-helminthics, Co-trimoxazole prophylaxis and highly active anti retroviral therapy have a protective effect against intestinal cryptosporidium. Screening for intestinal cryptosporidium is suggested in HIV infected children with recurrent abdominal pain, because of the statistically association. PMID- 26673563 TI - Editorial Comment on: Andrzej Smereczynski, Teresa Starzynska, Katarzyna Kolaczyk and Jozef Kladny Role of sonography in assessing complications after laparoscopic cholecystectomy. PMID- 26673564 TI - Lysine-Specific Demethylase 1A (KDM1A/LSD1): Product Recognition and Kinetic Analysis of Full-Length Histones. AB - Lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively. Although the active site is expanded compared to that of members of the greater amine oxidase superfamily, it is too sterically restricted to encompass the minimal 21-mer peptide substrate footprint. The remainder of the substrate/product is therefore expected to extend along the surface of KDM1A. We show that full-length histone H3, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor of KDM1A demethylation activity with a Ki of 18.9 +/- 1.2 nM, a value that is approximately 100-fold higher than that of the 21-mer peptide product. The relative H3 affinity is independent of preincubation time, suggesting that H3 rapidly reaches equilibrium with KDM1A. Jump dilution experiments confirmed the increased binding affinity of full-length H3 was at least partially due to a slow off rate (koff) of 1.2 * 10(-3) s(-1), corresponding to a half-life (t1/2) of 9.63 min, and a residence time (tau) of 13.9 min. Independent affinity capture surface plasmon resonance experiments confirmed the tight-binding nature of the H3/KDM1A interaction, revealing a Kd of 9.02 +/- 2.3 nM, a kon of (9.3 +/- 1.5) * 10(4) M(-1) s(-1), and a koff of (8.4 +/- 0.3) * 10(-4) s(-1). Additionally, no other core histones exhibited inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Together, these data suggest that KDM1A likely contains a histone H3 secondary specificity element on the enzyme surface that contributes significantly to its recognition of substrates and products. PMID- 26673565 TI - CD4+CD25 high Foxp3+ Treg deficiency in a Brazilian patient with Gaucher disease and lupus nephritis. AB - Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients. PMID- 26673566 TI - Guanidinium Pairing Facilitates Membrane Translocation. AB - Ab initio free energy calculations of guanidinium pairing in aqueous solution confirm the counterintuitive conjecture that the like-charge ion pair is thermodynamically stable. Transferring the guanidinium pair to the inside of a POPC lipid bilayer, like-charge ion pairing is found to occur also inside the membrane defect. It is found to contribute to the nonadditivity of ion transfer, thereby facilitating the presence of ions inside the bilayer. The effect is quantified by free energy decomposition and comparison with ammonium ions, which do not form a stable pair. The presence of two charges inside the center of the bilayer leads to the formation of a pore. Potential consequences for cell penetrating peptides and ion conduction are drawn. PMID- 26673567 TI - Isotonic Regression Based-Method in Quantitative High-Throughput Screenings for Genotoxicity. AB - Quantitative high-throughput screenings (qHTSs) for genotoxicity are conducted as part of comprehensive toxicology screening projects. The most widely used method is to compare the dose-response data of a wild-type and DNA repair gene knockout mutants, using model-fitting to the Hill equation (HE). However, this method performs poorly when the observed viability does not fit the equation well, as frequently happens in qHTS. More capable methods must be developed for qHTS where large data variations are unavoidable. In this study, we applied an isotonic regression (IR) method and compared its performance with HE under multiple data conditions. When dose-response data were suitable to draw HE curves with upper and lower asymptotes and experimental random errors were small, HE was better than IR, but when random errors were big, there was no difference between HE and IR. However, when the drawn curves did not have two asymptotes, IR showed better performance (p < 0.05, exact paired Wilcoxon test) with higher specificity (65% in HE vs. 96% in IR). In summary, IR performed similarly to HE when dose-response data were optimal, whereas IR clearly performed better in suboptimal conditions. These findings indicate that IR would be useful in qHTS for comparing dose response data. PMID- 26673569 TI - Entomofaunal Succession Patterns on Burnt and Unburnt Rabbit Carrion. AB - The influence of burning on the decomposition of rabbit carcasses and on insect succession was investigated in three different habitats (agricultural, desert, and urban) in order to provide data for estimating the postmortem interval (PMI). Each site had six carcasses divided into two groups of three rabbits, with the carcasses in one group being partially burned, while the others were not burned. Carrion reached the dry stage within 5 d in the desert and urban habitats and 13 d in the agricultural habitat. The unburnt and burnt carcasses also decomposed at a similar rate in the three study habitats. Adult dipteran and coleopteran insects were collected daily. A total of 24 species and 2,381 specimens were collected; of these, 732 specimens from 21 species were taken from the partially burnt carcasses and 1,649 specimens from 21 species from the unburnt carcasses. There were significantly distinct insect communities between the agricultural habitat and the desert and urban habitats. There were also significant differences in the insect communities between the decay stage and other stages, with fresh and dry stages recording the lowest number of insects. There were some species which only presented themselves during the decay stage of decomposition, namely, Platypalpus sp., Desmometopa varipalpis Malloch, Atherigona orientalis (Schiner), Atherigona yorki Deeming, Musca sorbens Weidemann, and Onthophagus nitidulus Klug. In addition, there were significant distinctions in the insect communities between unburnt carcasses and burnt carcasses. The presence of these distinctions means that it is possible to estimate the PMI from partially burnt rabbit carcasses. PMID- 26673568 TI - Daily transcriptome changes reveal the role of nitrogen in controlling microcystin synthesis and nutrient transport in the toxic cyanobacterium, Microcystis aeruginosa. AB - BACKGROUND: While transcriptomics have become a valuable tool for linking physiology and ecology in aquatic microbes, the temporal dynamics of global transcriptomic patterns in Microcystis have rarely been assessed. Furthermore, while many microbial studies have explored expression of nutrient transporter genes, few studies have concurrently measured nutrient assimilation rates. Here, we considered how the global transcriptomic patterns and physiology of the cyanobacterium, Microcystis aeruginosa, changed daily as cells were grown from replete to deficient nitrogen (N) conditions and then back to replete conditions. RESULTS: During N deprivation, Microcystis downregulated genes involved in photosynthesis and respiration, carbon acquisition, lipid metabolism, and amino acid biosynthesis while upregulating genes involved in N acquisition and transport. With increasing N stress, both the strength of expression and number of genes being differentially expressed increased, until N was restored at which point these patterns reversed. Uptake of (15)N-labeled nitrate, ammonium and urea reflected differential expression of genes encoding transporters for these nutrients, with Microcystis appearing to preferentially increase transcription of ammonium and urea transporters and uptake of these compounds during N deprivation. Nitrate uptake and nitrate transporter expression were correlated for one set of transporters but not another, indicating these were high and low affinity nitrate transporters, respectively. Concentrations of microcystin per cell decreased during N deprivation and increased upon N restoration. However, the transcript abundance of genes involved in the synthesis of this compound was complex, as microcystin synthetase genes involved in peptide synthesis were downregulated under N deprivation while genes involved in tailoring and transport were upregulated, suggesting modification of the microcystin molecule under N stress as well as potential alternative functions for these genes and/or this toxin. CONCLUSIONS: Collectively, this study highlights the complex choreography of gene expression, cell physiology, and toxin synthesis that dynamic N levels can elicit in this ecologically important cyanobacterium. Differing expression patterns of genes within the microcystin synthetase operon in response to changing N levels revealed the potential limitations drawing conclusions based on only one gene in this operon. PMID- 26673571 TI - Novel strategies against Candida biofilms: interest of synthetic compounds. AB - A biofilm is a consortium of microbial cells that are attached to a substratum or an interface. It should be considered a reservoir that may induce serious infections. Indeed, Candidaspp. biofilms may be involved in the persistence or worsening of some chronic inflammatory diseases as well as in systemic infections, which may lead to high morbidity and mortality rates. New strategies are currently being explored, utilizing several synthetic compounds to prevent or fight these Candida biofilms. This article focuses on active synthetic compounds classified with regards to their modes of action: inhibition of early adherence phase, inhibition or control of biofilm maturation and finally elimination of already formed biofilms. Some of them show promise in fighting biofilm. PMID- 26673572 TI - Evaluation of the First Year of National Reporting on a New Healthcare Personnel Influenza Vaccination Performance Measure by US Hospitals. AB - One thousand hospitals were surveyed on a new measure of healthcare personnel influenza vaccination for the 2012-2013 influenza season. Facilities found it easier to collect data on employees than nonemployees; larger facilities reported more challenges than smaller facilities. Barriers may decrease over time as facilities become accustomed to the measure. PMID- 26673570 TI - Synthetic biology for pharmaceutical drug discovery. AB - Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell-cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. PMID- 26673573 TI - Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature. AB - BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38 year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity. PMID- 26673574 TI - Analysis of the American Society of Anesthesiologists Physical Status Classification System and Caprini Risk Assessment Model in Predicting Venous Thromboembolic Outcomes in Plastic Surgery Patients. AB - BACKGROUND: Venous thromboembolism (VTE) can be a fatal outcome of plastic surgery. Risk assessment models attempt to determine a patient's risk, yet few studies have compared different models in plastic surgery patients. OBJECTIVE: The authors investigated preoperative ASA physical status and 2005 Caprini scores to determine which model was more predictive of VTE. METHODS: A retrospective chart review examined 1801 patients undergoing contouring and reconstructive procedures from January 2008 to January 2012. Patients were grouped into risk tiers for ASA scores (1-2 = low, 3+ = high) with 2 cutoffs for Caprini scores (1 4 = low, 5+ high; 1-5 = low, 6+ = high), then re-stratified into 3 tiers using Caprini score cutoffs (1-4 = low, 5-8 = high, 9+ = highest; 1-5 = low, 6-8 = high, 9+ = highest). Median scores of VTE patients were compared to those without VTE. Odds ratio and chi-squared analyses were performed. RESULTS: Of the 1598 patients included in the study, 1.50% developed VTE. Median ASA scores differed significantly between comparison groups but Caprini scores did not vary regardless of cutoff. When examining the 2-tiered Caprini scores, using low risk = 1-5 showed a significant relationship between risk tier and DVT development (P = 0.0266). CONCLUSION: The ASA system yielded the highest odds ratio of VTE development between low and high-risk patients. The Caprini model captured more patients with VTE in its high-risk category. Combining the two models for a more heuristic approach to preoperative care may identify patients at higher risk. LEVEL OF EVIDENCE: 4 Risk. PMID- 26673575 TI - Treatment of Prominent Ears with an Implantable Clip System: A Pilot Study. AB - BACKGROUND: The earFoldTM implantable clip system is a new treatment for prominent ears using an implant made from nickel-titanium alloy, forged into a predetermined shape. The implant is fixed to the cartilage then released, causing the cartilage to fold back. OBJECTIVES: The study aimed to test the safety and behaviour of the implant in vivo. METHODS: This was a Phase 1, prospective, nonrandomised study. Thirty-nine patients were recruited, from 7 to 57 years of age (22 adults and 17 children). Thirty-seven patients were followed up for a minimum of 18 months. A total of 131 implants was used to treat 75 ears. All treatments were performed under local anaesthetic. RESULTS: Eighteen patients asked for their implants to be left in place permanently. Twenty-one patients agreed to have their implants removed at 6, 12, or 18 months after insertion. Complications affected 8 patients and included extrusion, infection, hypertrophic scarring, and Spock-ear formation. No new complications have arisen in any of the patients since the conclusion of the study, up to a maximum of 47 months. Patients were overwhelmingly satisfied with the outcome of treatment. CONCLUSIONS: earFold can be used as a permanent implant to correct prominence of the human ear. It is best suited for treating prominent ears with a poorly formed or absent antihelical fold. The procedure is quick and predictable with a complication rate comparable to suture-based otoplasty techniques. PMID- 26673576 TI - Visual, Physiological, and Aesthetic Factors and Pitfalls in Asian Blepharoplasty. AB - Double eyelid surgery to create an upper-lid crease in Asian patients is one of the more popular aesthetic surgeries among people of Asian descent. Much has been written about the myriad methods, but little has been written about the underlying factors that predispose a patient to complications and suboptimal results. This article touches on some of the possible errors in placement of crease height in upper blepharoplasty and the pitfalls that can be associated with permanent placement of nondissolvable sutures that encircle the complex layers of the upper eyelid, as well as the ideal eyelid crease wound closure and its biodynamics. One should consider these factors in any form of upper eyelid procedure, as they are not merely applicable to upper blepharoplasty. PMID- 26673578 TI - Direct Observation of Photoinduced Charge Separation in Ruthenium Complex/Ni(OH)2 Nanoparticle Hybrid. AB - Ni(OH)2 have emerged as important functional materials for solar fuel conversion because of their potential as cost-effective bifunctional catalysts for both hydrogen and oxygen evolution reactions. However, their roles as photocatalysts in the photoinduced charge separation (CS) reactions remain unexplored. In this paper, we investigate the CS dynamics of a newly designed hybrid catalyst by integrating a Ru complex with Ni(OH)2 nanoparticles (NPs). Using time resolved X ray absorption spectroscopy (XTA), we directly observed the formation of the reduced Ni metal site (~60 ps), unambiguously demonstrating CS process in the hybrid through ultrafast electron transfer from Ru complex to Ni(OH)2 NPs. Compared to the ultrafast CS process, the charge recombination in the hybrid is ultraslow (?50 ns). These results not only suggest the possibility of developing Ni(OH)2 as solar fuel catalysts, but also represent the first time direct observation of efficient CS in a hybrid catalyst using XTA. PMID- 26673577 TI - Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. AB - BACKGROUND: Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin+/-bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2 negative metastatic breast cancer. TRIAL DESIGN: In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple negative breast cancer. METHODS: In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: <=1 versus>1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg*min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg*min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the "winner" of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: <=1 versus >1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression free survival; secondary endpoints include blinded, independently-assessed overall response rate, overall survival, disease control rate, duration of response, and safety. Biomarker and circulating tumor-cell exploratory analyses and quality-of-life assessments will also be performed. A list of approving ethical bodies was provided in Additional file 1. DISCUSSION: The tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01881230 . Date of registration: 17 June 2013. PMID- 26673579 TI - Standards of the Polish Ultrasound Society - update. Sonomammography examination. AB - The use of BIRADS classification has been recommended in sonomammography examinations in Poland since the year 2010. It was developed by the Polish Ultrasound Society and published in Ultrasound Examinations Standards of the Polish Ultrasound Society. Standards, based on BIRADS-usg classification, introduced uniformity in breast ultrasound examination descriptions and in the terminology of pathological lesions in breasts. BIRADS-usg classification takes into account breast morphological structure elements and pathological focal lesions in them. It enables the distinction between benign lesions and lesions suspected of being malignant. It contains information on the malignancy risk of focal lesions and proposals of diagnostic-therapeutic algorithms (including biopsy) in relation to lesions of different character. The Polish Ultrasound Society recommends performing prophylactic sonomammography examinations every 12 months in women over the age of 30 because of the increasing breast cancer morbidity in women from all age groups. In this article a spectrum of focal changes in breasts are presented within the relevant BIRADS-usg classification categories. The features of ultrasound morphology, enabling them to be classified to particular categories of BIRADS-usg classification are discussed. Management algorithms which may help clinicians to diagnose breast cancer and to treat it are proposed. Elements of medical history, physical examination, recommended techniques of sonomammography examination performance, technical parameters of ultrasound machine and examination description standards are presented. This article was prepared based on the Ultrasound Examination Standards of the Polish Ultrasound Society which was published in 2011 and updated. It contains numerous pictures visualizing BIRADS-usg classification. PMID- 26673581 TI - Early resuscitation practices. PMID- 26673580 TI - MEK and PI3K inhibition in solid tumors: rationale and evidence to date. AB - PI3K-AKT-mTOR and Ras-Raf-MEK-ERK are the most commonly altered oncogenic pathways in solid malignancies. There has been a lot of enthusiasm to develop inhibitors to these pathways for cancer therapy. Unfortunately, the antitumor activities of single-agent therapies have generally been disappointing, excluding B-Raf mutant melanoma and renal cell cancer. Preclinical studies have suggested that concurrent targeting of the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is an active combination in various solid malignancies. In the current work, we review the preclinical data of the PI3K and MEK dual targeting as a cancer therapy and the results of early-phase clinical trials, and propose future directions. PMID- 26673582 TI - Research activities among Australian and New Zealand anaesthetists. PMID- 26673583 TI - Viscoelastic point-of-care testing to guide transfusion and antithrombotic therapy in perioperative and critically ill patients: are all parameters created equal? PMID- 26673584 TI - Pitfalls in haemodynamic monitoring in the postoperative and critical care setting. AB - Haemodynamic monitoring is a vital part of daily practice in anaesthesia and intensive care. Although there is evidence to suggest that goal-directed therapy may improve outcomes in the perioperative period, which haemodynamic targets we should aim at to optimise patient outcomes remain elusive and controversial. This review highlights the pitfalls in commonly used haemodynamic targets, including arterial blood pressure, central venous pressure, cardiac output, central venous oxygen saturation and dynamic haemodynamic indices. Evidence suggests that autoregulation in regional organ circulation may change either due to chronic hypertension or different disease processes such as traumatic brain injury, cerebrovascular ischaemia or haemorrhage; this will influence the preferred blood pressure target. Central venous pressure can be influenced by multiple pathophysiological factors and, unless central venous pressure is very low, it is rarely useful as a predictor for fluid responsiveness. Central venous oxygen saturation can be easily increased by a high arterial oxygen tension, making it useless as a surrogate marker of good cardiac output or systemic oxygen delivery in the presence of hyperoxaemia. Many dynamic haemodynamic indices have been reported to predict fluid responsiveness, but they all have their own limitations. There is also insufficient evidence to support that giving fluid until the patient is no longer fluid responsive can improve patient-centred outcomes. With the exception in the context of preventing contrast-induced nephropathy, large randomised controlled studies suggest that excessive fluid treatment may prolong duration of mechanical ventilation without preventing acute kidney injury in the critically ill. PMID- 26673585 TI - The role of an ambient pressure oxygen source during one-lung ventilation for thoracoscopic surgery. AB - Video-assisted thoracoscopic surgery is facilitated by prompt collapse of the non ventilated ('operated') lung, and interrupted and impeded if there is a need for oxygen (O2) delivery by continuous positive airways pressure in order to manage hypoxaemia. It has been proposed that connecting an ambient pressure O2 source to the airway of the non-ventilated lung at the time one-lung ventilation is initiated and before the chest is opened will, by avoiding entrainment of ambient nitrogen, serve to facilitate lung collapse. It has also been proposed that leaving the O2 source connected will enable, not only ongoing apnoeic oxygenation before the chest is opened, but also the thoracoscopic procedure to commence with the operated lung fully pre-oxygenated (with an inspired oxygen fraction of 1), and apnoeic oxygenation to continue throughout the operative procedure in those patients who exhibit a degree of small airways patency at ambient pressure. In reality, several factors can influence the speed of collapse of the operated lung, and very many factors can influence the incidence of hypoxaemia during one lung ventilation. It therefore appears unlikely that the necessary evidence to support these proposals will be forthcoming from randomised clinical studies on large numbers of patients. Rather, the necessary evidence may only be provided by specifically designed within-patient clinical measurement studies. Nevertheless, it is argued that, in the meantime, there is already sufficient rationale for an ambient pressure O2 source to be connected to the airway of the non-ventilated lung, and for it to remain connected for the duration of one-lung ventilation. PMID- 26673586 TI - A trial of nebulised heparin to limit lung injury following cardiac surgery. AB - Cardiac surgery with cardiopulmonary bypass triggers an acute inflammatory response in the lungs. This response gives rise to fibrin deposition in the microvasculature and alveoli of the lungs. Fibrin deposition in the microvasculature increases alveolar dead space, while fibrin deposition in alveoli causes shunting. We investigated whether prophylactic nebulised heparin could limit this form of lung injury. We undertook a single-centre double-blind randomised trial. Forty patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomised to prophylactic nebulised heparin (50,000 U) or placebo. The primary endpoint was the change in arterial oxygen levels over the operative period. Secondary endpoints included end-tidal CO2, the alveolar dead space fraction and bleeding complications. We found nebulised heparin did not improve arterial oxygen levels. Nebulised heparin was, however, associated with a lower alveolar dead space fraction (P <0.05) and lower tidal volumes at the end of surgery (P <0.01). Nebulised heparin was not associated with bleeding complications. In conclusion, prophylactic nebulised heparin did not improve oxygenation, but was associated with evidence of better alveolar perfusion and CO2elimination at the end of surgery. PMID- 26673587 TI - Activities of a Medical Emergency Team: a prospective observational study of 795 calls. AB - Relatively few papers have examined specific causes for Medical Emergency Team (MET) review and the assessment and management undertaken by the MET. The aim of our study was to describe the type of patients who require MET review, the reasons such reviews are requested and the subsequent immediate management of these patients. Our prospective single-centre observational study was conducted in a university-affiliated tertiary hospital in New Zealand between October 2012 and September 2013. Each trigger for MET review was assessed separately to allow analysis of the main associated underlying conditions and interventions. Seven hundred and ninety-five MET calls were generated for 630 patients. Mean patient age was 64 years. Sixty percent of all calls involved medical patients. There was a marked diurnal variation in the incidence of MET calls, with MET calls more likely during the daytime and evening compared to the night. The most common triggers for MET calls were an unresponsive or fitting patient (25.2%), tachycardia (24.2%), and an Early Warning Score of 8 or more (22.8%). Neurological causes (30.7%), cardiovascular failure (hypotension, pulmonary oedema) (26.7%), respiratory failure (22.6%), and sepsis (19.2%) were the most common underlying conditions. One of these top four conditions was present in nearly all patients (99.2%). The majority of MET calls were made for a relatively small number of underlying conditions and triggers, supporting the concept of 'MET syndromes'. The pattern of interventions is predictable from the triggering condition. This may guide education and training of ward staff to improve detection of deteriorating patients and prevent or pre-emptively manage causes of such deterioration prior to MET criteria being reached. The association between time of day and crisis recognition suggests the hospital system does not reliably detect deteriorating patients. This questions the adequacy of monitoring of deteriorating patients on hospital wards. PMID- 26673588 TI - Intravenous fluid bolus therapy: a bi-national survey of critical care nurses' self-reported practice. AB - Knowledge of critical care nurses' intravenous fluid bolus therapy (FBT) practice remains underexplored. Using a multi-choice online survey conducted between September and October 2014, we sought to describe the self-reported practice of critical care nurses located in Australia and New Zealand. Two hundred and ninety five critical care nurses responded to the survey with most practising in adult ICUs. Overall, 0.9% saline solution was the preferred solution for FBT. However, more Australian than New Zealand respondents preferred 'albumin 4%' (31% versus 3.6%, P <0.01) for FBT. In contrast, more New Zealand respondents preferred 'Plasma-Lyte(r)' (33.3% versus 6.4%, P <0.01). Half of the respondents defined FBT as 250 ml administered as quickly as possible. However, FBT volumes ranged from 100 ml to >1000 ml and administration duration from as quickly as possible to 60 minutes. In response to FBT, almost half of the respondents expected an increase in mean arterial pressure of between 11 to 20 mmHg. Similarly, >40% expected a central venous pressure increase >3 mmHg, >70% expected a urinary output increase of 0.5 to 1.0 ml/kg/hr, and >60% expected a decrease in heart rate of >11 /min. Overall, 0.9% saline remains the most common solution for FBT, but there are significant national differences in the preference for albumin and Plasma-Lyte. A volume of 250 ml defines a fluid bolus, with a range from 100 ml to >1000 ml, and speed of delivery from stat to 60 minutes. Most nurses expect substantial physiological effects with FBT. PMID- 26673589 TI - Procedural pain does not raise plasma levels of cortisol or catecholamines in adult intensive care patients after cardiac surgery. AB - The gold standard for quantification of pain is a person's self-report. However, we need objective parameters for pain measurement when intensive care patients, for example, are not able to report pain themselves. An increase in pain is currently thought to coincide with an increase in stress hormones. This observational study investigated whether procedure-related pain is associated with an increase of plasma cortisol, adrenaline, and noradrenaline. In 59 patients receiving intensive care after cardiac surgery, cortisol, adrenaline, and noradrenaline plasma levels were measured immediately before and immediately after patients were turned for washing, either combined with the removal of chest tubes or not. Numeric rating scale scores were obtained before, during, and after the procedure. Unacceptably severe pain (numeric rating scale >= 4) was reported by seven (12%), 26 (44%), and nine (15%) patients, before, during and after the procedure, respectively. There was no statistically significant association between numeric rating scale scores and change in cortisol, adrenaline, and noradrenaline plasma levels during the procedure. Despite current convictions that pain coincides with an increase in stress hormones, procedural pain was not associated with a significant increase in plasma stress hormone levels in patients who had undergone cardiac surgery. Thus, plasma levels of cortisol, adrenaline, and noradrenaline seem unsuitable for further research on the measurement of procedural pain. PMID- 26673590 TI - Day 3 versus Day 1 disseminated intravascular coagulation score among sepsis patients: a prospective observational study. AB - The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of DIC at day 1 (<24 hours post-sepsis diagnosis) and day 3 (48 to 72 hours) were investigated among patients with sepsis. The International Society of Thrombosis and Haemostasis criteria for DIC were used. Among 381 patients initially screened, 219 were enrolled in this study and the incidences of overt DIC were 27.9% and 30.1% on day 1 and day 3, respectively. Patients with pneumonia had a lower incidence of DIC on day 1, but a higher hospital mortality rate compared to those with non-pneumonia sepsis. In multivariate models, although day 1 and day 3 DIC scores were not associated with hospital mortality after adjusting for existing severity scores, the change in DIC scores (odds ratio 1.862; 95% confidence interval 1.061 to 3.266) exhibited a significant association. Day 3 DIC scores were more accurate in predicting hospital mortality than day 1 DIC scores (P <0.001), especially in patients with non-pneumonia sepsis. However, DIC scores did not give additional discriminative power to the existing prognostic scores in predicting mortality of patients with sepsis. In conclusion, the change in DIC score was significantly associated with hospital mortality. Patients with pneumonia sepsis had a lower incidence of DIC on day 1, despite their higher disease severity and mortality rate, compared to those with other sources of sepsis. PMID- 26673592 TI - Obesity prevalence and associated outcomes in cardiothoracic patients: a single centre experience. AB - The objective of this study was to investigate the prevalence of obesity and its relationship with adverse outcomes in ICU cardiothoracic patients. We performed a retrospective analysis of cardiothoracic patients admitted to The Royal Melbourne Hospital ICU between 2002 and 2014. Eight thousand and sixty-four patients who underwent coronary artery bypass, valve replacement/repair, or both, were divided into six categories of body mass index using World Health Organization criteria. Prevalence of obesity over time in the ICU was measured and compared to prevalence of obesity in the adult Australian population. The association between obesity and adverse postoperative outcomes was then analysed. Obesity is currently 1.2 times more prevalent in the Royal Melbourne Hospital ICU cardiothoracic patients than in the adult Australian population, with 33.5% of patients having a body mass index =30 kg/m(2). Over time, this was relatively constant, but an increasing proportion were morbidly obese. Obesity, but not morbid obesity, was associated with reduced 30-day mortality (odds ratio [OR] 0.41). Both obese and morbidly obese patients had reduced odds of return to theatre for bleeding (OR 0.49 and OR 0.19, respectively), but increased odds of new-onset renal failure (OR 1.62 and OR 3.17, respectively). Morbidly obese patients had double the odds of an ICU stay longer than 14 days (OR 2.05). In summary, a growing proportion of our obese ICU patients are morbidly obese, with a dramatically increased length of ICU stay. This has major implications for resource allocation in the ICU, and may inform modelling of future bed utilisation. Obesity, but not morbid obesity, conferred a mortality benefit. PMID- 26673591 TI - Characteristics of sepsis-induced cardiac dysfunction using speckle-tracking echocardiography: a feasibility study. AB - Septic cardiomyopathy is commonly encountered in patients with severe sepsis and septic shock. This study explores whether novel global and segmental echocardiographic markers of myocardial deformation, using two-dimensional speckle tracking, are associated with adverse sepsis outcomes. We conducted a retrospective observational feasibility study, at a tertiary care centre, of patients admitted to the ICU with a diagnosis of sepsis who underwent an echocardiogram within the first week of sepsis diagnosis. Data were collected on chamber dimensions, systolic and diastolic function, demographics, haemodynamics, and laboratory parameters. Global and segmental left ventricular longitudinal strain (LVLS) and tissue mitral annular displacement (TMAD) were assessed on 12 left ventricular segments and six mitral annulus segments in apical views, respectively. We explored associations of abnormal LVLS and TMAD with duration of mechanical ventilation, hospital length of stay, and mortality. Fifty-four patients were included. Global LVLS was not associated with any of the primary study endpoints. However, reduced systolic LVLS of the basal anterior segment was associated with in-hospital mortality. There was a suggestion that patients with a reduced global TMAD were associated with an increased risk of mortality and a short length of hospital stay but these associations were not statistically significant. Reduced global LVLS was associated with lower ejection fraction. Reduced global TMAD was associated with reduced global and segmental LVLS, reduced left ventricular ejection fraction, and increased left ventricular end systolic and end-diastolic volumes. Speckle-tracking echocardiography can be performed feasibly in patients in sepsis. Global and segmental left ventricular deformation indices are associated with ejection fraction. Further studies need to evaluate the ability of these new indices to predict sepsis outcomes. PMID- 26673593 TI - Discordance between ROTEM(r) clotting time and conventional tests during unfractionated heparin-based anticoagulation in intensive care patients on extracorporeal membrane oxygenation. AB - We hypothesised that ROTEM(r) (Basel, Switzerland) INTEM(r) (ROTEM, Basel, Switzerland) clotting time (CT) would have good agreement with activated partial thromboplastin time (aPTT) in determining whether a dose adjustment should be made to the unfractionated heparin (UFH) infusion in patients on extracorporeal membrane oxygenation. All patients treated with extracorporeal membrane oxygenation over a five-year period were included for data analysis. Retrospective analysis was performed of prospectively collected data points, wherein aPTT, activated CT and ROTEM was performed simultaneously to monitor UFH based anticoagulation. Two hundred data points were available for analysis. Turnaround time was shortest for activated CT followed by ROTEM and aPTT. Despite achieving therapeutic aPTT targets, the majority (>50%) of INTEM CT results were within normal limits. The aPTT and INTEM CT results correlated weakly (r=0.31, 95% confidence interval [0.17, 0.43]) and there was no agreement between the directional changes of aPTT and INTEM CT results on successive days (x2 =2.33, P=0.17). Due to relative insensitivity, INTEM CT-guided UFH titration was estimated to result in a 289% increase in incidence of up-titration, over aPTT guided titration. The INTEM CT results (r=0.36, 95% confidence interval [0.23, 0.48]) correlated weakly with UFH infusion rates. The UFH infusion rate only explained 13% variability in INTEM CT values. While haemorrhagic complications were frequent, no major clotting complications were encountered. Our results demonstrated that aPTT and INTEM CT do not provide equivalent information to guide UFH infusion rate titration during extracorporeal membrane oxygenation. Our study suggests caution regarding the use of ROTEM for guiding UFH-based anticoagulation as it may lead to excessive UFH exposure. PMID- 26673594 TI - Enhanced Protein-Energy Provision via the Enteral Route Feeding (PEPuP) protocol in critically ill surgical patients: a multicentre prospective evaluation. AB - Suboptimal levels of feeding in critically ill patients are associated with poor clinical outcomes. The Enhanced Protein-Energy Provision via the Enteral Route Feeding (PEPuP) protocol was developed to improve nutritional delivery in the critically ill and has been studied in several hospitals. However, the experience with this protocol in surgical patients is limited to date. The objective of this analysis was to describe the experience with this protocol in surgical patients. We analysed observational patient data obtained from the 2013 International Nutrition Survey. We compared nutritional practices and outcomes of patients admitted for surgical and medical reasons to ICUs in sites that implemented the PEPuP protocol. We used surgical ICU patients in non-PEPuP sites as a concurrent control group. In sites that implemented the PEPuP protocol, surgical patients received a smaller proportion of prescribed calories (43% versus 61%, P=0.004) and protein (38% versus 57%, P=0.002) compared to medical patients. When compared to the cohort of surgical patients from control sites, the surgical patients from PEPuP sites received similar amounts of calories and protein. Although surgical PEPuP patients were more likely to receive trophic and volume-based feeds compared to surgical patients in control sites, other aspects of the PEPuP protocol were not adequately implemented. We conclude that nutritional delivery to surgical patients remains inadequate and the PEPuP protocol seems ineffective in improving nutritional intake in this population. Further research to determine methods of optimising PEPuP protocol implementation and adherence in surgery patients is needed. PMID- 26673595 TI - Potential donor families' experiences of organ and tissue donation-related communication, processes and outcome. AB - We aimed to describe the experiences of families of potential organ and tissue donors eligible for donation after circulatory death or brain death. Forty-nine family members of potential donors from four Melbourne hospitals were interviewed to assess their experiences of communication, processes and the outcomes of donation. Interviews were recorded, transcribed verbatim and analysed thematically. Families expressed a range of perspectives on themes of communication, hospital processes and care, the processes of consent and donation and reflected on decisions and outcomes. They expressed satisfaction overall with communication when receiving bad news, discussing death and donation. Honest and frank communication and being kept up-to-date and prepared for potential outcomes were important aspects for families, especially those of post circulatory death donors. Participants reported high levels of trust in healthcare professionals and satisfaction with the level of care received. Many donor families indicated the process was lengthy and stressful, but not significantly enough to adversely affect their satisfaction with the outcome. Both the decision itself and knowing others' lives had been saved provided them with consolation. No consenting families, and only some non-consenting families, regretted their decisions. Many expressed they would benefit from a follow-up opportunity to ask questions and clarify possible misunderstandings. Overall, while experiences varied, Australian families valued frank communication, trusted health professionals, were satisfied with the care their family member received and with donation processes, despite some apparent difficulties. Family satisfaction, infrequently assessed, is an important outcome and these findings may assist education for Australian organ donation professionals. PMID- 26673596 TI - Prolonged fasting of children before anaesthesia is common in private practice. AB - Fasting guidelines for children are well established. Despite these guidelines, previous studies have shown children are often fasted for prolonged periods before anaesthesia, potentially causing discomfort and distress. Moreover, recent publications indicate shorter fasting times for oral clear fluids in children may be safe. We audited fasting times of children having elective surgery at a local large private hospital that provides care for both adults and children. We gave feedback and education to our caregivers, then repeated the audit. Data were collected from 307 children (age 6.0 +/- 4.1 years) in an initial eight-week audit, and from 153 children (age 6.7 +/- 4.5 years) in a follow-up four-week audit. We found fasting durations were excessive in many children. Sixty-two percent of children in each audit fasted longer than four hours for clear fluids. Children on morning lists fasted longer than children on afternoon lists. Fasting from solids was also excessively long. In the initial audit, 30% fasted more than 12 hours for solids, including 18 who last ate more than 16 hours before surgery. Data from the follow-up audit were similar. We conclude that fasting of children at our hospital is excessive, despite our efforts to shorten the duration. We suspect that our hospital is not the only one with a high incidence of prolonged fasting for children and suggest possible solutions. PMID- 26673597 TI - Intentions and barriers to research activities among Australian and New Zealand anaesthetists: a Survey. AB - A voluntary, anonymous, cross-sectional online survey was conducted among 997 Fellows of the Australian and New Zealand College of Anaesthetists, using an electronic questionnaire. Details about their demographics, employment, research experience and barriers they had encountered, their perception about research and their future intentions to participate in research, were collected. The survey response rate was 24.6%. At the time of the survey, 29% of the survey respondents were involved in research. Respondents currently involved in research were more likely to be practising at a tertiary hospital, to have previously presented at conferences, to believe in the importance of research and to intend to undertake further research training (P <0.05). Time constraints were the most commonly cited reason for not currently performing research. Those who were involved in research spent about 6.3 more hours per week in public practice than those who were not (P=0.012) and had about 4.4 more hours per week of non-clinical time (P <0.001). In terms of barriers encountered during previous projects, 91% of the respondents cited methodological issues, which included complicated ethics approval processes, difficulty in coordinating teams or recruiting participants, non-compliant patients and difficulty in publishing. Sixty-three percent of those surveyed believed more exposure to research activities during training would increase the number of anaesthetists involved in research and scholarly activities. Through this survey, we have identified several areas that, if satisfactorily addressed, could enhance interest and participation in research amongst anaesthetists in Australia and New Zealand. PMID- 26673598 TI - Serendipitous use of terlipressin. PMID- 26673599 TI - Serendipitous use of terlipressin. PMID- 26673600 TI - Use of a right-sided double lumen tube for lung isolation in a patient with Kartagener's syndrome. PMID- 26673601 TI - Monitoring the appropriateness of surgical antibiotic prophylaxis prescribing in Australia: valid and meaningful indicators provide 'data for action'. PMID- 26673602 TI - Anaphylaxis to sugammadex diagnosed by skin prick testing using both sugammadex and a sugammadex-rocuronium mixture. PMID- 26673603 TI - Leptin levels and clinical outcomes in patients with systemic inflammatory response syndrome. PMID- 26673604 TI - Incentive spirometry through tracheostomy stoma. PMID- 26673605 TI - Reducing finger cuts when opening glass ampoules. PMID- 26673606 TI - Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles. AB - Copper-free click reactions between a dibenzoazocine derivative and azides derived from 5-methyluridine were investigated. The non-catalyzed reaction yielded both regioisomers in an approximately equivalent ratio. The NMR spectra of each regioisomer revealed conformational isomery. The ratio of isomers was dependent on the type of regioisomer and the type of solvent. The synthesis of various analogs, a detailed NMR study and computational modeling provided evidence that the isomery was dependent on the interaction of the azocine and pyrimidine parts. PMID- 26673607 TI - Why consider contrast-enhanced ultrasound (ce-US) in children?: Editorial comment on: M.M. Wozniak, A. Pawelec, A.P. Wieczorek, M.M. Zajaczkowska, H. Borzecka and P. Nachulewicz 2D/3D/4D contrast-enhanced voiding urosnography in the diagnosis and monitoring of treatment of vesicoureteral reflux in children - can it replace voiding cystourethrography? PMID- 26673608 TI - Correction: Self-Regulation of Anterior Insula with Real-Time fMRI and Its Behavioral Effects in Obsessive-Compulsive Disorder: A Feasibility Study. PMID- 26673609 TI - Context-Dependent Diversity-Effects of Seaweed Consumption on Coral Reefs in Kenya. AB - Consumers and prey diversity, their interactions, and subsequent effects on ecosystem function are important for ecological processes but not well understood in high diversity ecosystems such as coral reefs. Consequently, we tested the potential for diversity-effects with a series of surveys and experiments evaluating the influence of browsing herbivores on macroalgae in Kenya's fringing reef ecosystem. We surveyed sites and undertook experiments in reefs subject to three levels of human fishing influence: open access fished reefs, small and recently established community-managed marine reserves, and larger, older government-managed marine reserves. Older marine reserves had a greater overall diversity of herbivores and browsers but this was not clearly associated with reduced macroalgal diversity or abundance. Experiments studying succession on hard substrata also found no effects of consumer diversity. Instead, overall browser abundance of either sea urchins or fishes was correlated with declines in macroalgal cover. An exception was that the absence of a key fish browser genus, Naso, which was correlated with the persistence of Sargassum in a marine reserve. Algal selectivity assays showed that macroalgae were consumed at variable rates, a product of strong species-specific feeding and low overlap in the selectivity of browsing fishes. We conclude that the effects of browser and herbivore diversity are less than the influences of key species, whose impacts emerge in different contexts that are influenced by fisheries management. Consequently, identifying key herbivore species and managing to protect them may assist protecting reef functions. PMID- 26673610 TI - Mesenteric changes in an ultrasound examination can facilitate the diagnosis of neuroendocrine tumors of the small intestine. AB - Neuroendocrine tumors make up an interesting pathology of a variable clinical picture, prognosis, localization, endocrine activity and degree of malignancy. AIM: The aim of this paper is to assess whether ultrasonography can be helpful in diagnosing neuroendocrine tumors in the small intestine by analyzing changes in the mesentery. MATERIAL AND METHODS: From 1996 to 2013, we encountered 17 patients (9 women and 8 men at the mean age of 57) with a neuroendocrine tumor in the small intestine. The diagnosis was confirmed in all patients by pathomorphological examinations. All retrospectively analyzed patients (n =17) had an abdominal US examination conducted in accordance with the previously mentioned protocol. RESULTS: Primary neuroendocrine tumors were visualized ultrasonography in 13 of 17 patients (76.5%). In the remaining 4 patients, tumors in the small bowel were diagnosed in CT enteroclysis (n = 3) and conventional enteroclysis (n = 1). Somatostatin receptor scintigraphy and CT enteroclysis supplemented the ultrasound result by providing information about the stage of the disease in 7 cases. In most of the 17 patients with a neuroendocrine tumor diagnosed by ultrasound (n = 11, 64.7%), changes in the mesentery were prevailing pathological signs that raised suspicion and, consequently, helped localize the primary lesion. The hypoechoic mesenteric lymph nodes were the greatest (9-18 mm), well-circumscribed, and the largest of them showed signs of vascularization. The size of hypoechoic lesions in the mesentery ranged from 25 to 53 mm. These lesions showed moderate blood flow. All of them were single, usually poorly circumscribed; two lesions showed slight calcifications. CONCLUSIONS: In an abdominal US examination, 2/3 of patients with neuroendocrine tumors in the small bowel manifest secondary lesions in the mesentery which are easier to visualize than the primary focus. 30% of them are manifested as hypoechoic masses. The detection of such lesions should prompt the search for the primary focus in the small intestine. PMID- 26673611 TI - Oxygen changes drive non-uniform scaling in Drosophila melanogaster embryogenesis. AB - We previously demonstrated that, while changes in temperature produce dramatic shifts in the time elapsed during Drosophila melanogaster embryogenesis, the relative timing of events within embryogenesis does not change. However, it was unclear if this uniform scaling is an intrinsic property of developing embryos, or if it is specific to thermal fluctuations. To investigate this, here we characterize the embryonic response to changes in oxygen concentration, which also impact developmental rate, using time-lapse imaging, and find it fundamentally different from the temperature response. Most notably, changes in oxygen levels drive developmental heterochrony, with the timing of several morphological processes showing distinct scaling behaviors. Gut formation is severely slowed by decreases in oxygen, while head involution and syncytial development are less impacted than the rest of development, and the order of several developmental landmarks is inverted at different oxygen levels. These data reveal that the uniform scaling seen with changes in temperature is not a trivial consequence of adjusting developmental rate. The developmental rate changes produced by changing oxygen concentrations dwarf those induced by temperature, and greatly impact survival. While extreme temperatures increase early embryo mortality, mild hypoxia increases arrest and death during mid embryogenesis and mild hyperoxia increases survival over normoxia. PMID- 26673613 TI - Green Urine Due to Propofol: A Case Report with Review of Literature. AB - The change in the colour of urine is a known occurrence in an intensive care setting and is always a cause of concern to the clinicians who have to differentiate between benign and pathological causes. Herein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia. The green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs. This discolouration of urine is a rare (less than 1% cases) but a benign side effect of Propofol, which is non-nephrotoxic and gets reversed after discontinuation of the drug. PMID- 26673614 TI - An exploration of role model influence on adult nursing students' professional development: A phenomenological research study. AB - Patients' expectations of being cared for by a nurse who is caring, competent, and professional are particularly pertinent in current health and social care practice. The current drive for NHS values-based recruitment serves to strengthen this. How nursing students' development of professionalism is shaped is not fully known, though it is acknowledged that their practice experience strongly shapes behaviour. This study (in 2013-14) explored twelve adult nursing students' lived experiences of role modelling through an interpretive phenomenological analysis approach, aiming to understand the impact on their development as professional practitioners. Clinical nurses influenced student development consistently. Some students reported that their experiences allowed them to learn how not to behave in practice; a productive learning experience despite content. Students also felt senior staff influence on their development to be strong, citing 'leading by example.' The impact of patients on student professional development was also a key finding. Through analysing information gained, identifying and educating practice-based mentors who are ready, willing, and able to role model professional attributes appear crucial to developing professionalism in nursing students. Those involved in nurse education, whether service providers or universities, may wish to acknowledge the influence of clinical nurse behaviour observed by students both independent of and in direct relation to care delivery and the impact on student nurse professional development. A corollary relates to how students should be guided and briefed/debriefed to work with a staff to ensure their exposure to a variety of practice behaviours. PMID- 26673612 TI - Cognition, Emotion and Behavior in Children with Tourette's Syndrome and Children with ADHD-Combined Subtype-A Two-Year Follow-Up Study. AB - OBJECTIVE: This two-year follow-up study investigates the course of and association among measures of cognitive control, focused attention, decision making and symptom severity (anxiety, depression and behavior) in children and adolescents with Tourette's Syndrome (TS) or Attention-Deficit/Hyperactivity Disorder-Combined subtype (ADHD-C). METHOD: 19 children with TS, 33 with ADHD-C, and 50 typically developing children (TDC) were examined with a battery of psychometric measures and rating forms at baseline and two-years later. RESULTS: All three groups improved likewise in measures of cognitive control over time, whereas only the TDC improved in focused attention. The group of children with TS with comorbidities performed more similar to the children with ADHD-C in cognitive control at T1 and T2, whereas the children with TS without comorbidities performed more similar to the TDC in cognitive control at T1 and T2. In the decision-making task, the children with TS (with or without comorbidities) preferred a safer strategy in selecting advantageous choices than the children with ADHD-C and the TDC at T2. Children with TS and children with ADHD-C showed higher symptoms of anxiety and depression and more problems with emotional control compared with TDC at both time points. Finally, children with ADHD-C self-reported more depression symptoms than those with TS at both assessments. For the TS group, safer decision-making was related to better emotional control, and this relationship was stronger for the TS subgroup without comorbidities. CONCLUSION: This study emphasizes the importance of addressing symptoms of anxiety and depression in children with TS or ADHD-C, identifying the effect of comorbidities in children with TS, and that children with TS or ADHD-C likely differ in their sensitivity to reinforcement contingencies. PMID- 26673615 TI - Ultrasound of soft tissue masses of the hand. AB - Most soft tissue mass lesions of the hand are benign. Ganglia are the commonest lesions encountered, followed by giant cell tumors of the tendon sheath. Malignant tumors are rare. Often a specific diagnosis can be achieved on imaging by considering the location and anatomical relations of the lesion within the hand or wrist, and assessing its morphology. Magnetic resonance imaging is an excellent modality for evaluating soft tissue tumors with its multiplanar capability and ability to characterize tissue. Ultrasound plays a complementary role to MRI. It is often the initial modality used for assessing masses as it is cheap and available, and allows reliable differentiation of cystic from solid lesions, along with a real time assessment of vascularity. This review describes the US appearances of the most frequently encountered soft tissue masses of the wrist and hand, correlating the findings with MRI where appropriate. PMID- 26673616 TI - Spatial-temporal epidemiology of human Salmonella Enteritidis infections with major phage types (PTs 1, 4, 5b, 8, 13, and 13a) in Ontario, Canada, 2008-2009. AB - BACKGROUND: In Ontario and Canada, the incidence of human Salmonella enterica serotype Enteritidis (S. Enteritidis) infections have increased steadily during the last decade. Our study evaluated the spatial and temporal epidemiology of the major phage types (PTs) of S. Enteritidis infections to aid public health practitioners design effective prevention and control programs. METHODS: Data on S. Enteritidis infections between January 1, 2008 and December 31, 2009 were obtained from Ontario's disease surveillance system. Salmonella Enteritidis infections with major phage types were classified by their annual health region level incidence rates (IRs), monthly IRs, clinical symptoms, and exposure settings. A scan statistic was employed to detect retrospective phage type specific spatial, temporal, and space-time clusters of S. Enteritidis infections. Space-time cluster cases' exposure settings were evaluated to identify common exposures. RESULTS: 1,336 cases were available for analysis. The six most frequently reported S. Enteritidis PTs were 8 (n = 398), 13a (n = 218), 13 (n = 198), 1 (n = 132), 5b (n = 83), and 4 (n = 76). Reported rates of S. Enteritidis infections with major phage types varied by health region and month. International travel and unknown exposure settings were the most frequently reported settings for PT 5b, 4, and 1 cases, whereas unknown exposure setting, private home, food premise, and international travel were the most frequently reported settings for PT 8, 13, and 13a cases. Diarrhea, abdominal pain, and fever were the most commonly reported clinical symptoms. A number of phage type specific spatial, temporal, and space-time clusters were identified. Space-time clusters of PTs 1, 4, and 5b occurred mainly during the winter and spring months in the North West, North East, Eastern, Central East, and Central West regions. Space-time clusters of PTs 13 and 13a occurred at different times of the year in the Toronto region. Space-time clusters of PT 8 occurred at different times of the year in the North West and South West regions. CONCLUSIONS: Phage type specific differences in exposure settings, and spatial-temporal clustering of S. Enteritidis infections were demonstrated that might guide public health surveillance of disease outbreaks. Our study methodology could be applied to other foodborne disease surveillance data to detect retrospective high disease rate clusters, which could aid public health authorities in developing effective prevention and control programs. PMID- 26673617 TI - NOVA1 inhibition by miR-146b-5p in the remnant tissue microenvironment defines occult residual disease after gastric cancer removal. AB - Occult residual disease in remnant tissues could be the cause of tumor relapse. To identify signal molecules and target cells that may be indicative of occult residual disease within a remnant microenvironment, proximal resection margin tissues of gastric cancers were used, as these correspond to the nearest remnant tissues after gastrectomy. Increased miR-146b-5p in the remnant microenvironment was determined to be a strong risk factor for tumor relapse and poor survival rate. NOVA1, a target gene of miR-146b-5p, was decreased in remnant tissues of patients with a poor prognosis. NOVA1 was enriched in stromal spindle cells such as fibroblasts within normal tissues. In non-neoplastic inflammation, such as gastritis, NOVA1 was highly enriched in T lymphocytes and stromal spindle cells, while expression of this protein was frequently decreased in those types of cells within gastric cancer tissues. Particularly, decreased NOVA1 in T cells within the gastric cancer tissues was correlated with decreased FOXP3-positive regulatory T cells and was associated with poor patient prognosis. In vitro analysis showed that the NOVA1 gene was inhibited by miR-146b-5p. In immune cells as well as stromal spindle cells, decreased NOVA1, possibly inhibited by miR-146b 5p, is a candidate biomarker predicting poor prognosis of gastric cancer patients and is also a biomarker of occult residual disease in remnant tissues after gastric cancer removal. PMID- 26673618 TI - Differential expression of neurogenes among breast cancer subtypes identifies high risk patients. AB - The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2 enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID- 26673619 TI - MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC). AB - Here we explore the role of microRNA-372 (miR-372) in tumorigenesis and development of endometrial adenocarcinoma (EC) and analyze the underlying mechanism. We found that miR-372 expression is much lower in EC than normal endometrial specimens. Cell function experiments demonstrated that miR-372 overexpression suppressed cell proliferation, migration, and invasion, and led to a G1 phase arrest and promoted the apoptosis of endometrial carcinoma cells in vitro. The nude mouse xenograft assay demonstrated that miR-372 overexpression suppressed tumor growth. RT-PCR and Western blot assays detected the expression of known targets of miR-372 in other malignant tumors and found Cyclin A1 and Cyclin-dependent Kinase 2 (CDK2) was downregulated by miR-372. Bioinformatic predictions and dual-luciferase reporter assays found that RhoC was a possible target of miR-372. RT-PCR and Western blot assays demonstrated that miR-372 transfection reduced the expression of RhoC, matrix metalloproteinase 2 (MMP2) and MMP9, while it increased the expression of cleaved poly (ADP ribose) polymerase (PARP) and bcl-2-associated X protein (Bax). The cell function experiments that transfected siRNA with RhoC showed the same trend as those which were transfected with miR-372. Taken together, our results demonstrated for the first time that miR-372 suppresses tumorigenesis and the development of EC; RhoC is a new and potentially important therapeutic target. PMID- 26673620 TI - MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5 fluorouracil treatment by targeting KSR1. AB - Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR 497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response. PMID- 26673622 TI - A long-day light program accelerates seasonal coat changes but is without effect on semen and metabolic parameters in Shetland pony stallions. AB - Horses are seasonal breeders, and robust breeds may exhibit a winter hypometabolism when kept under semiferal conditions. In this study, we analyzed the effects of artificial long days on rectal temperature, heart rate, heart rate variability, hematology, coat changes, semen parameters, and plasma testosterone concentrations in Shetland stallions stabled overnight and assigned to a control group (CON, n = 9) kept under natural photoperiod, and a treatment group exposed to a long-day light program from 15 December to 20 March (AL, n = 9). During the 8-month study, rectal temperature, heart rate, and heart rate variability at no time differed between groups. Plasma total protein (P < 0.05), hematocrit, leukocyte, and lymphocyte counts (P < 0.001) first increased and then decreased during the study period but did not differ between groups. Length of the guard hair decreased over time (P < 0.001) and this decrease occurred earlier in AL than in CON stallions (time * group P < 0.001). Hair regrowth was faster in CON than in AL stallions (over time P < 0.001, time * group P < 0.001). Total sperm count increased from January to April (AL) and May (CON; P < 0.001) but did not differ between groups. Sperm motility and percentage of membrane-intact spermatozoa showed no clear seasonal changes and semen parameters did not differ between groups. In conclusion, Shetland stallions showed seasonal variations in hair coat and total sperm count but only changes in hair coat but not semen parameters were advanced by a long-day light program. PMID- 26673623 TI - Behaviour-Related Scalar Habitat Use by Cape Buffalo (Syncerus caffer caffer). AB - Studies of habitat use by animals must consider behavioural resource requirements at different scales, which could influence the functional value of different sites. Using Cape buffalo (Syncerus caffer caffer) in the Okavango Delta, Botswana, we tested the hypotheses that behaviour affected use between and within habitats, hereafter referred to as macro- and microhabitats, respectively. We fitted GPS-enabled collars to fifteen buffalo and used the distances and turning angles between consecutive fixes to cluster the resulting data into resting, grazing, walking and relocating behaviours. Distance to water and six vegetation characteristic variables were recorded in sites used for each behaviour, except for relocating, which occurred too infrequently. We used multilevel binomial and multinomial logistic regressions to identify variables that characterised seasonally-preferred macrohabitats and microhabitats used for different behaviours. Our results showed that macrohabitat use was linked to behaviour, although this was least apparent during the rainy season, when resources were most abundant. Behaviour-related microhabitat use was less significant, but variation in forage characteristics could predict some behaviour within all macrohabitats. The variables predicting behaviour were not consistent, but resting and grazing sites were more readily identifiable than walking sites. These results highlight the significance of resting, as well as foraging, site availability in buffalo spatial processes. Our results emphasise the importance of considering several behaviours and scales in studies of habitat use to understand the links between environmental resources and animal behavioural and spatial ecology. PMID- 26673624 TI - Design of a Photoactive Hybrid Bilayer Dielectric for Flexible Nonvolatile Organic Memory Transistors. AB - Organic field-effect transistors (OFETs) featuring a photoactive hybrid bilayer dielectric (PHBD) that comprises a self-assembled monolayer (SAM) of photochromic diarylethenes (DAEs) and an ultrathin solution-processed hafnium oxide layer are described here. We photoengineer the energy levels of DAE SAMs to facilitate the charging and discharging of the interface of the two dielectrics, thus yielding an OFET that functions as a nonvolatile memory device. The transistors use light signals for programming and electrical signals for erasing (<=3 V) to produce a large, reversible threshold-voltage shift with long retention times and good nondestructive signal processing ability. The memory effect can be exercised by more than 10(4) memory cycles. Furthermore, these memory cells have demonstrated the capacity to be arrayed into a photosensor matrix on flexible plastic substrates to detect the spatial distribution of a confined light and then store the analog sensor input as a two-dimensional image with high precision over a long period of time. PMID- 26673621 TI - Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas. AB - Over half of BRAFV600E melanomas display intrinsic resistance to BRAF inhibitors, in part due to adaptive signaling responses. In this communication we ask whether BRAFV600E melanomas share common adaptive responses to BRAF inhibition that can provide clinically relevant targets for drug combinations. We screened a panel of 12 treatment-naive BRAFV600E melanoma cell lines with MAP Kinase pathway inhibitors in pairwise combination with 58 signaling inhibitors, assaying for synergistic cytotoxicity. We found enormous diversity in the drug combinations that showed synergy, with no two cell lines having an identical profile. Although the 6 lines most resistant to BRAF inhibition showed synergistic benefit from combination with lapatinib, the signaling mechanisms by which this combination generated synergistic cytotoxicity differed between the cell lines. We conclude that adaptive responses to inhibition of the primary oncogenic driver (BRAFV600E) are determined not only by the primary oncogenic driver but also by diverse secondary genetic and epigenetic changes ("back-seat drivers") and hence optimal drug combinations will be variable. Because upregulation of receptor tyrosine kinases is a major source of drug resistance arising from diverse adaptive responses, we propose that inhibitors of these receptors may have substantial clinical utility in combination with inhibitors of the MAP Kinase pathway. PMID- 26673625 TI - Giant negative magnetoresistance induced by the chiral anomaly in individual Cd3As2 nanowires. AB - Dirac electronic materials beyond graphene and topological insulators have recently attracted considerable attention. Cd3As2 is a Dirac semimetal with linear dispersion along all three momentum directions and can be viewed as a three-dimensional analogue of graphene. By breaking of either time-reversal symmetry or spatial inversion symmetry, the Dirac semimetal is believed to transform into a Weyl semimetal with an exotic chiral anomaly effect, however the experimental evidence of the chiral anomaly is still missing in Cd3As2. Here we show a large negative magnetoresistance with magnitude of -63% at 60 K and -11% at 300 K in individual Cd3As2 nanowires. The negative magnetoresistance can be modulated by gate voltage and temperature through tuning the density of chiral states at the Fermi level and the inter-valley scatterings between Weyl nodes. The results give evidence of the chiral anomaly effect and are valuable for understanding the Weyl fermions in Dirac semimetals. PMID- 26673626 TI - Stafne's Bone Cavity: A Diagnostic Challenge. AB - Stafne's bone cavity is a rare, asymptomatic, unilateral oval shaped radiolucent defect in the posterior region of the mandible below the inferior alveolar canal. The prevalence ranges from 0.10% to 0.48% and more common in males. It is mostly an incidental finding on panoramic radiograph. This radiolucency is considered to be a deformity of the medial cortex. This article presents five rare cases of Stafne's bone cavity which were referred for opinion or wrongly diagnosed by practicing health professionals as jaw tumour leading to psychological distress in these patients. This article also focuses on reviewing the published literature, differential diagnosis along with use of various diagnostic imaging resources for this bone defect and to add five new Indian cases to the literature. PMID- 26673627 TI - Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma. AB - AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher's exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589 37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070 6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment. CONCLUSION: The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival, but a higher radiation dose improved the survival. PMID- 26673629 TI - EliA is required for inducing the stearyl alcohol-mediated expression of secretory proteins and production of polyester in Ralstonia sp. NT80. AB - Addition of stearyl alcohol to the culture medium of Ralstonia sp. NT80 induced expression of a significant amount of secretory lipase. Comparative proteomic analysis of extracellular proteins from NT80 cells grown in the presence or absence of stearyl alcohol revealed that stearyl alcohol induced expression of several secretory proteins including lipase, haemolysin-coregulated protein and nucleoside diphosphate kinase. Expression of these secreted proteins was upregulated at the transcriptional level. Stearyl alcohol also induced the synthesis of polyhydroxyalkanoate. Secretory protein EliA was required for all these responses of NT80 cells to stearyl alcohol. Accordingly, the effects of stearyl alcohol were significantly reduced in the eliA deletion mutant cells of NT80 (DeltaeliA). The remaining concentration of stearyl alcohol in the culture supernatant of the wild-type cells, but not that in the culture supernatant of the DeltaeliA cells, clearly decreased during the course of growth. These observed phenotypes of the DeltaeliA mutant were rescued by gene complementation. The results suggested that EliA is essential for these cells to respond to stearyl alcohol, and that it plays an important role in the recognition and assimilation of stearyl alcohol by NT80 cells. PMID- 26673628 TI - Interleukin-6 trans-signaling increases the expression of carcinoembryonic antigen-related cell adhesion molecules 5 and 6 in colorectal cancer cells. AB - BACKGROUND: Colorectal cancer (CRC) is among the five most frequent causes for cancer-related deaths in Europe. One of the most important tumor-associated antigens for CRC is carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), which is involved in cell adhesion, migration, anoikis, tumor invasion and metastasis. Its family member CEACAM6 is also upregulated in adenomas and carcinomas of the colon and an independent predictor of poor survival. Previous studies have reported a link between upregulation of CEACAM5 and interleukin-6 (IL-6). IL-6 plays an important role in CRC progression, and signaling is mediated via two pathways (classic and trans-signaling). However, this link could not be confirmed by other studies, and the role of IL-6 trans-signaling in the CEACAM5 upregulation has not been elucidated. Moreover, the impact of IL-6 on the expression of CEACAM6 has not yet been examined. METHODS: The expression of IL-6, IL-6 receptor (IL-6R), glycoprotein (gp) 130, CEACAM5 and CEACAM6 was analyzed by RT-PCR, Western blot, flow cytometry or qPCR. Colon cell lines were incubated with IL-6 or Hyper-IL-6 (mediating IL-6 trans-signaling), and subsequently, the expression of CEACAMs was determined by qPCR or Western blot. FLLL31, an inhibitor of the phosphorylation of signal transducer and activator of transcription-3 (STAT3), was used to determine the role of STAT3 phosphorylation. RESULTS: We confirmed that colon carcinoma cell lines express IL-6 and IL-6R. We observed only a weak upregulation of CEACAM5 and CEACAM6 by classic IL-6 signaling, but a strong increase by IL-6 trans-signaling. This upregulation depended on the phosphorylation of STAT3. CONCLUSIONS: Our data show the upregulation of the tumor-associated antigens CEACAM5/6 by trans-signaling of the pro-inflammatory cytokine IL-6. This mechanism may contribute to the tumor promoting role of IL-6 and could therefore be a target for therapeutic intervention in particular by specific inhibitors such as sgp130Fc. PMID- 26673630 TI - Gold Nanoparticles Deposited Polyaniline-TiO2 Nanotube for Surface Plasmon Resonance Enhanced Photoelectrochemical Biosensing. AB - A novel ternary composite composed of TiO2 nanotubes (TiONTs), polyaniline (PANI), and gold nanoparticles (GNPs) was prepared for photoelectrochemical (PEC) biosensing. PANI was initially coated on TiONTs with an oxidative polymerization method, and 12-phosphotungstic acid was then used as a highly localized photoactive reducing agent to deposit GNPs on TiONT-PANI. The morphology and composition of the composite were characterized by various spectroscopic and microscopic methods. Electrochemical impedance spectroscopy was also conducted to demonstrate the excellent electrical conductivity of the composite. A PEC biosensor was fabricated by immobilizing a mixture of lactate dehydrogenase and the composite onto ITO electrodes, which regenerated nicotinamide adenine dinucleotide (NAD(+)) to complete the enzymatic cycle and led to an improved method for PEC detection of lactate. Because of the surface plasmon resonance enhanced effect of GNPs, the electrochromic performance of PANI, and excellent conductivity and biocompatibility of the composite, this method showed a dynamic range of 0.5-210 MUM, sensitivity of 0.0401 MUA MUM(-1), and a detection limit of 0.15 MUM. PMID- 26673631 TI - Global Update and Trends of Hidden Hunger, 1995-2011: The Hidden Hunger Index. AB - BACKGROUND: Deficiencies in essential vitamins and minerals-also termed hidden hunger-are pervasive and hold negative consequences for the cognitive and physical development of children. METHODS: This analysis evaluates the change in hidden hunger over time in the form of one composite indicator-the Hidden Hunger Index (HHI)-using an unweighted average of prevalence estimates from the Nutrition Impact Model Study for anemia due to iron deficiency, vitamin A deficiency, and stunting (used as a proxy indicator for zinc deficiency). Net changes from 1995-2011 and population weighted regional means for various time periods are measured. FINDINGS: Globally, hidden hunger improved (-6.7 net change in HHI) from 1995-2011. Africa was the only region to see a deterioration in hidden hunger (+1.9) over the studied time period; East Asia and the Pacific performed exceptionally well (-13.0), while other regions improved only slightly. Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anemia due to iron deficiency persisted and even increased. INTERPRETATION: This analysis is critical for informing and tracking the impact of policy and programmatic efforts to reduce micronutrient deficiencies, to advance the global nutrition agenda, and to achieve the Millennium Development Goals (MDGs). However, there remains an unmet need to invest in gathering frequent, nationally representative, high-quality micronutrient data as we renew our efforts to scale up nutrition, and as we enter the post-2015 development agenda. FUNDING: Preparation of this manuscript was funded by Sight and Life. There was no funding involved in the study design, data collection, analysis, or decision to publish. PMID- 26673632 TI - Ultrasound and echocardiographic findings obtained in the second and third trimesters of gestation in fetuses with normal karyotype and increased nuchal translucency. AB - INTRODUCTION: Numerous papers have proven that an increased nuchal translucency is connected with a raised risk of chromosomal aberrations, but few analyses are related to the further state of fetuses with a normal karyotype. THE AIM OF THE STUDY: The aim of the study was to estimate the risk of cardiac defects and other developmental disorders in fetuses with increased nuchal translucency and normal findings of a standard cytogenetic examination. METHODS: The authors carried out a retrospective analysis of 5183 examinations of 3376 patients who reported to the Department of Diagnosis and Prophylaxis of Congenital Malformations in the Polish Mother's Memorial Hospital in Lodz in the period from January 2008 to March 2011 for prenatal ultrasound and echocardiographic examinations. The authors analyzed the results of the examinations performed in the second and third trimesters of gestation in fetuses with an increased nuchal translucency of >=3 mm in the first trimester and with a normal karyotype. RESULTS: Fifty-seven patients (1.7% of the examined group) fulfilled the criteria necessary to be included in the study. In 31 pregnant women (54%) structural defects or anomalies of the fetus were found. Cardiac anomalies were detected in 17 fetuses (29.8%). The authors detected various types of cardiac defects such as tetralogy of Fallot, ventricular septal defect, atrioventricular septal defect, transposition of the great arteries and hypoplastic left heart syndrome. CONCLUSIONS: In more than half of the fetuses with an increased nuchal translucency (NT >= 3 mm) and a normal karyotype, developmental defects of various organs appeared in the further course of pregnancy: mainly heart defects that were either isolated, or accompanied other anomalies. PMID- 26673633 TI - Learning the ABCs of pregnancy and newborn care through mobile technology. AB - BACKGROUND: The diffusion of mobile phones in low- and middle-income countries has taken place faster than any other infrastructural development. Mobile Midwife, a mobile application implemented in Ghana in 2010, sends timely messages in local languages to registered expectant mothers and new parents. The field of mobile health (mHealth) is severely underresearched, yet it can be an alternative for improving health systems and the ways in which health services are delivered. OBJECTIVE: Our goal was to investigate the role that Mobile Midwife technology has played in the lives of pregnant and nursing mothers in Awutu Senya District, Ghana. DESIGN: A total of three focus group discussions and 19 individual interviews were conducted. Discussions and interviews were recorded, transcribed verbatim from the local language to English, and analyzed by means of qualitative content analysis at the manifest and latent levels. RESULTS: The main findings show that while oscillating between modern and traditional practices, women gradually gained trust in Mobile Midwife's counselling and attempted to balance between myths and reality regarding nutrition in pregnancy. In addition, their decisions to seek essential obstetric care were enhanced by Mobile Midwife's advice. Women also felt strengthened in their understanding of the importance of seeking professional care during pregnancy and childbirth as well as recognizing signs of ill health in the newborn. CONCLUSIONS: The findings indicate that Mobile Midwife could be an excellent tool in working towards the improvement of maternal health. Mobile Midwife will hopefully contribute to the stepwise achievement of the Sustainable Development Goals extended from the Millennium Development Goals, which expire at the end of 2015. There is a need for strong political will from key stakeholders, to embark in the field of mHealth as a complementary means to strengthen health systems. PMID- 26673634 TI - Delayed complication of abdominal aortic stent: a rare complication. AB - We hereby present a case of recurrent abdominal aortic aneurysm due to endoleak to outline complications and secondary intervention strategies post endovascular aneurysm repair. PMID- 26673635 TI - Urine Output Assessment as a Clinical Quality Measure. AB - Urine output (UO) is a relevant marker of kidney function and an independent marker of serum creatinine. Although oliguria can be the result of transitory changes in volume status or due to external influences, such as drug administration, UO is currently included as a criterion to diagnose and stage acute kidney injury (AKI). In clinical practice, the potential of earlier alert of kidney injury with frequent assessment of UO can help patient screening and risk assessment. In this review, we will discuss recent studies applying UO for AKI diagnosis and prognostication and propose methods to assess UO and improve quality of care. PMID- 26673636 TI - Enumeration of circulating fibrocytes for clinical use in asthma by an optimized single-platform flow cytometry assay. AB - BACKGROUND: Elevated numbers of circulating fibrocytes are associated with inadequately controlled asthma, poor response to available therapies, and increased risk of adverse outcomes. The lack of reliable and clinically applicable assays precludes a proper evaluation of blood fibrocyte count as a prognostic biomarker in asthma. This report concerns the use of a multiparameter flow cytometry assay for the enumeration of fibrocytes in the whole blood. METHODS: Consenting fibrocyte donors were 19 patients with asthma well controlled by current treatment, 16 patients with treatment-resistant asthma, 9 patients with transiently uncontrolled asthma and 14 age-matched normal individuals. Blood sampling was performed once in patients with transiently uncontrolled asthma and twice, at an interval of one week, in the other subjects. The assay was performed in 100 MUl of whole blood and involved a sequential gating strategy and absolute fibrocyte counting with a single instrument (single-platform assay). RESULTS: The quantification of circulating fibrocytes by this assay was analytically and clinically valid. In individuals with stable clinical conditions, the repeatability of blood fibrocyte counts over one week was good. The intraclass correlation coefficient was 0.939 and 96.88% of the total variability reflected on-average differences among the tested subjects. Stabilized blood samples could be stored at 4 degrees C for up to 96 h before processing. CONCLUSIONS: The novel assay for the enumeration of fibrocytes in the whole blood is reliable and clinically applicable. GENERAL SIGNIFICANCE: This report demonstrates the validity and reliability of the first optimized assay for the enumeration of circulating fibrocytes in multicenter clinical trials. PMID- 26673637 TI - Plenty of moustaches but not enough women: cross sectional study of medical leaders. AB - OBJECTIVES: To draw attention to sex related disparities in academic medical leadership by investigating the representation of female leaders compared with leaders with moustaches. DESIGN: Cross sectional analysis. SETTING: Academic medical departments in the United States. PARTICIPANTS: Clinical department leaders (n=1018) at the top 50 US medical schools funded by the National Institutes of Health (NIH). MAIN OUTCOME MEASURES: The proportions of female leaders and moustachioed leaders across institutions and specialties (n=20). Additionally, the moustache index: the proportion of women compared with the proportion of moustaches, analyzed with multinomial logistic regression models. RESULTS: Women accounted for 13% (137/1018) of department leaders at the top 50 NIH funded medical schools in the US. Moustachioed leaders accounted for 19% (190/1018). The proportion of female department leaders ranged from 0% (0/20) to 26% (5/19) across institutions and 0% (0/53) to 36% (19/53) across specialties. Only seven institutions and five specialties had more than 20% of female department leaders. The overall moustache index of all academic medical departments studied was 0.72 (95% confidence interval 0.58 to 0.90; P=0.004). Only six of 20 specialties had more women than moustaches (moustache index >1). CONCLUSIONS: Moustachioed individuals significantly outnumber women as leaders of medical departments in the US. We believe that every department and institution should strive for a moustache index >=1. Known, effective, and evidence based policies to increase the number of women in leadership positions should be prioritized. PMID- 26673638 TI - Case Study of an Unsustainable Community-Academic Partnership: Toward Core Standards for the Structure of Emerging Participatory Research. AB - This report retrospectively examines the structure of an emerging community academic participatory research (PR) partnership that was not sustainable, despite attempts to adhere to PR principles and demonstrable success in research outcomes. The influence of community and academic parent organizations on the PR process and outcomes is presented in the context of the Donabedian Model. We dissected the structural elements contributed by parent organizations to forming the structure of the PR partnership (memorandum of understanding, policy environment, human resources and effort, community and academic resources, expertise and experience, and funding) and explored the influence of potential and actual conflicts on the PR partnership's sustainability. The effect of potential and actual conflict on the PR process and quality of PR outcomes is discussed. Based on this, we conclude by proposing seven core standards for the establishment and development of emerging community-academic PR partnerships. PMID- 26673639 TI - Fractional flow reserve-guided percutaneous coronary intervention: where to after FAME 2? AB - Fractional flow reserve (FFR) is a well-validated clinical coronary physiological parameter derived from the measurement of coronary pressures and has drastically changed revascularization decision-making in clinical practice. Nonetheless, it is important to realize that FFR is a coronary pressure-derived estimate of coronary blood flow impairment. It is thereby not the same as direct measures of coronary flow impairment that determine the occurrence of signs and symptoms of myocardial ischemia. This consideration is important, since the FAME 2 study documented a limited discriminatory power of FFR to identify stenoses that require revascularization to prevent adverse events. The physiological difference between FFR and direct measures of coronary flow impairment may well explain the findings in FAME 2. This review aims to address the physiological background of FFR, its ambiguities, and its consequences for the application of FFR in clinical practice, as well as to reinterpret the diagnostic and prognostic characteristics of FFR in the light of the recent FAME 2 trial outcomes. PMID- 26673640 TI - Hydroxylation of Longiborneol by a Clm2-Encoded CYP450 Monooxygenase to Produce Culmorin in Fusarium graminearum. AB - A second structural gene required for culmorin biosynthesis in the plant pathogen Fusarium graminearum is described. Clm2 encodes a regio- and stereoselective cytochrome P450 monooxygenase for C-11 of longiborneol (1). Clm2 gene disruptants were grown in liquid culture and assessed for culmorin production via HPLC evaporative light scattering detection. The analysis indicated a complete loss of culmorin (2) from the liquid culture of the DeltaClm2 mutants. Culmorin production resumed in a DeltaClm2 complementation experiment. A detailed analysis of the secondary metabolites extracted from the large-scale liquid culture of disruptant DeltaClm2D20 revealed five new natural products: 3-hydroxylongiborneol (3), 5-hydroxylongiborneol (4), 12-hydroxylongiborneol (5), 15 hydroxylongiborneol (6), and 11-epi-acetylculmorin (7). The structures of the new compounds were elucidated by a combination of HRMS, 1D and 2D NMR, and X-ray crystallography. PMID- 26673641 TI - Gut Microbiota and Hepatocellular Carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of liver diseases such as those related to viral hepatitis and liver cirrhosis. The gut liver axis is gaining increasing attention as a key pathophysiological mechanism responsible for the progression of HCC. Here, we will review the data from the published literature to address the association between HCC and gut microbiota. SUMMARY: The presence of high levels of endotoxemia in the blood results in portal hypertension and ensuing hepatocyte damage, thus leading to the development of HCC. Probiotics can be used to treat or prevent the progression of HCC, because they may decrease the counts of gut microbiota and thus improve the endotoxemia. KEY MESSAGE: Increased bacterial translocation can result in endotoxemia, which may play a critical role in the progression of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention in HCC. PRACTICAL IMPLICATIONS: Breakdown in intestinal barrier function and bacterial overgrowth are main events in the development of HCC. When the intestinal barrier function is disrupted, large amounts of bacterial products can enter the liver and induce inflammation through their receptors, leading to liver diseases. Altering the gut microflora has been proposed as an adjunctive therapy to reduce bacterial translocation and prevent progression of HCC. The purpose of this review is to discuss the relationship between gut microbiota and HCC in both pathogenesis and treatment by probiotics. PMID- 26673642 TI - Exclusive Csp(3)-Csp(3) vs Csp(2)-Csp(3) Reductive Elimination from Pt(IV) Governed by Ligand Constraints. AB - Selective reductive elimination of ethane (Csp(3)-Csp(3) RE) was observed following bromide abstraction and subsequent thermolysis of a Pt(IV) complex bearing both Csp(3)- and Csp(2)-hybridized hydrocarbyl ligands. Through a comparative experimental and theoretical study with two other Pt(IV) complexes featuring greater conformational flexibility of the ligand scaffold, we show that the rigidity of a meridionally coordinating ligand raises the barrier for Csp(2) Csp(3) RE, resulting in unprecedented reactivity. PMID- 26673643 TI - Expanded HTA: Enhancing Fairness and Legitimacy. AB - All societies face the need to make judgments about what interventions (both public health and personal medical) to provide to their populations under reasonable resource constraints. Their decisions should be informed by good evidence and arguments from health technology assessment (HTA). But if HTA restricts itself to evaluations of safety, efficacy, and cost-effectiveness, it risks being viewed as insufficient to guide health decision-makers; if it addresses other issues, such as budget impact, equity, and financial protection, it may be accused of overreaching. But the risk of overreaching can be reduced by embedding HTA in a fair, deliberative process that meets the conditions required by accountability for reasonableness. PMID- 26673644 TI - Care Seeking Patterns of STIs-Associated Symptoms in Iran: Findings of a Population-Based Survey. AB - BACKGROUND: Understanding the prevalence of symptoms associated with sexually transmitted infections (STIs) and how care is sought for those symptoms are important components of STIs control and prevention. People's preference between public and private service providers is another important part of developing a well-functioning STIs surveillance system. METHODS: This cross-sectional survey was carried out in spring 2011, using a nonrandom quota sample of 1190 participants (52% female) in 4 densely-populated cities of Tehran, Kerman, Shiraz, and Babol. Two predictive logistic regression models were constructed to assess the association between the socio-demographic determinants (independent variables) and the dependent variables of history of STIs-associated symptom and seeking care. RESULTS: Around 57% (677 out of 1190; men: 29.70% and women: 81.80%) had experienced at least one STIs-associated symptom during the previous year. History of experiencing STIs-associated symptoms among men, was negatively significantly associated with older age (adjusted odds ratio [AOR] = 0.34, CI 95%: 0.17-0.67). Women who were married, in older ages, and had higher educations were more likely to report a recent (past year) STIs symptom, however all were statistically insignificant in both bivariate and multivariable models. Among those who have had STIs-associated symptoms in the last year, 31.15% did nothing to improve their symptoms, 8.03% attempted self-treatment by over-the-counter (OTC) medications or traditional remedies, and 60.93% sought care in health facilities. In both bivariate and multivariable analyses, care seeking among men was insignificantly associated with any of the collected demographic variables. Care seeking among women was positively significantly associated with being married (AOR = 2.48, 95% CI: 1.60-3.84). CONCLUSION: The reported prevalence of STIs-associated symptoms among our participants is concerning. A considerable number of participants had delayed seeking care and treatment or self-medicated. People should be informed about their sexual health and the consequences of delaying or avoiding seeking care for STIs. Participants preferred seeking care at private sectors which calls for engaging both public and private health sectors for reporting and following up STIs cases. PMID- 26673645 TI - The Relationship Between the Scope of Essential Health Benefits and Statutory Financing: An International Comparison Across Eight European Countries. AB - BACKGROUND: Both rising healthcare costs and the global financial crisis have fueled a search for policy tools in order to avoid unsustainable future financing of essential health benefits. The scope of essential health benefits (the range of services covered) and depth of coverage (the proportion of costs of the covered benefits that is covered publicly) are corresponding variables in determining the benefits package. We hypothesized that a more comprehensive health benefit package may increase user cost-sharing charges. METHODS: We conducted a desktop research study to assess the interrelationship between the scope of covered health benefits and the height of statutory spending in a sample of 8 European countries: Belgium, England, France, Germany, the Netherlands, Scotland, Sweden, and Switzerland. We conducted a targeted literature search to identify characteristics of the healthcare systems in our sample of countries. We analyzed similarities and differences based on the dimensions of publicly financed healthcare as published by the European Observatory on Health Care Systems. RESULTS: We found that the scope of services is comparable and comprehensive across our sample, with only marginal differences. Cost-sharing arrangements show the most variation. In general, we found no direct interrelationship in this sample between the ranges of services covered in the health benefits package and the height of public spending on healthcare. With regard to specific services (dental care, physical therapy), we found indications of an association between coverage of services and cost-sharing arrangements. Strong variations in the volume and price of healthcare services between the 8 countries were found for services with large practice variations. CONCLUSION: Although reducing the scope of the benefit package as well as increasing user charges may contribute to the financial sustainability of healthcare, variations in the volume and price of care seem to have a much larger impact on financial sustainability. Policy-makers should focus on a variety of measures within an integrated approach. There is no silver bullet for addressing the sustainability of healthcare. PMID- 26673646 TI - Introducing New Priority Setting and Resource Allocation Processes in a Canadian Healthcare Organization: A Case Study Analysis Informed by Multiple Streams Theory. AB - BACKGROUND: In this article, we analyze one case instance of how proposals for change to the priority setting and resource allocation (PSRA) processes at a Canadian healthcare institution reached the decision agenda of the organization's senior leadership. We adopt key concepts from an established policy studies framework - Kingdon's multiple streams theory - to inform our analysis. METHODS: Twenty-six individual interviews were conducted at the IWK Health Centre in Halifax, NS, Canada. Participants were asked to reflect upon the reasons leading up to the implementation of a formal priority setting process - Program Budgeting and Marginal Analysis (PBMA) - in the 2012/2013 fiscal year. Responses were analyzed qualitatively using Kingdon's model as a template. RESULTS: The introduction of PBMA can be understood as the opening of a policy window. A problem stream - defined as lack of broad engagement and information sharing across service lines in past practice - converged with a known policy solution, PBMA, which addressed the identified problems and was perceived as easy to use and with an evidence-base from past applications across Canada and elsewhere. Conditions in the political realm allowed for this intervention to proceed, but also constrained its potential outcomes. CONCLUSION: Understanding in a theoretically-informed way how change occurs in healthcare management practices can provide useful lessons to researchers and decision-makers whose aim is to help health systems achieve the most effective use of available financial resources. PMID- 26673647 TI - Governance, Government, and the Search for New Provider Models. AB - A central problem in designing effective models of provider governance in health systems has been to ensure an appropriate balance between the concerns of public sector and/or government decision-makers, on the one hand, and of non governmental health services actors in civil society and private life, on the other. In tax-funded European health systems up to the 1980s, the state and other public sector decision-makers played a dominant role over health service provision, typically operating hospitals through national or regional governments on a command-and-control basis. In a number of countries, however, this state role has started to change, with governments first stepping out of direct service provision and now de facto pushed to focus more on steering provider organizations rather than on direct public management. In this new approach to provider governance, the state has pulled back into a regulatory role that introduces market-like incentives and management structures, which then apply to both public and private sector providers alike. This article examines some of the main operational complexities in implementing this new governance reality/strategy, specifically from a service provision (as opposed to mostly a financing or even regulatory) perspective. After briefly reviewing some of the key theoretical dilemmas, the paper presents two case studies where this new approach was put into practice: primary care in Sweden and hospitals in Spain. The article concludes that good governance today needs to reflect practical operational realities if it is to have the desired effect on health sector reform outcome. PMID- 26673648 TI - Accelerate Implementation of the WHO Global Code of Practice on International Recruitment of Health Personnel: Experiences From the South East Asia Region: Comment on "Relevance and Effectiveness of the WHO Global Code Practice on the International Recruitment of Health Personnel - Ethical and Systems Perspectives". AB - Strengthening the health workforce and universal health coverage (UHC) are among key targets in the heath-related Sustainable Development Goals (SDGs) to be committed by the United Nations (UN) Member States in September 2015. The health workforce, the backbone of health systems, contributes to functioning delivery systems. Equitable distribution of functioning services is indispensable to achieve one of the UHC goals of equitable access. This commentary argues the World Health Organization (WHO) Global Code of Practice on International Recruitment of Health Personnel is relevant to the countries in the South East Asia Region (SEAR) as there is a significant outflow of health workers from several countries and a significant inflow in a few, increased demand for health workforce in high- and middle-income countries, and slow progress in addressing the "push factors." Awareness and implementation of the Code in the first report in 2012 was low but significantly improved in the second report in 2015. An inter country workshop in 2015 convened by WHO SEAR to review progress in implementation of the Code was an opportunity for countries to share lessons on policy implementation, on retention of health workers, scaling up health professional education and managing in and out migration. The meeting noted that capturing outmigration of health personnel, which is notoriously difficult for source countries, is possible where there is an active recruitment management through government to government (G to G) contracts or licensing the recruiters and mandatory reporting requirement by them. According to the 2015 second report on the Code, the size and profile of outflow health workers from SEAR source countries is being captured and now also increasingly being shared by destination country professional councils. This is critical information to foster policy action and implementation of the Code in the Region. PMID- 26673649 TI - Is It More Important to Address the Issue of Patient Mobility or to Guarantee Universal Health Coverage in Europe?: Comment on "Regional Incentives and Patient Cross-Border Mobility: Evidence From the Italian Experience". AB - This paper discusses whether European institutions should devote so much attention and funding to cross-border healthcare or they should instead prioritise guaranteeing universal health coverage (UHC), "addressing inequalities" and tackling the effects of austerity measures. The paper argues through providing the evidence in both areas of research, that the priority at European level from a public health and social justice perspective should be to guarantee UHC for all the population living in Europe and prioritise protective action for those who are most in need. PMID- 26673650 TI - Policy Capacity for Health Reform: Necessary but Insufficient: Comment on "Health Reform Requires Policy Capacity". AB - Forest and colleagues have persuasively made the case that policy capacity is a fundamental prerequisite to health reform. They offer a comprehensive life-cycle definition of policy capacity and stress that it involves much more than problem identification and option development. I would like to offer a Canadian perspective. If we define health reform as re-orienting the health system from acute care to prevention and chronic disease management the consensus is that Canada has been unsuccessful in achieving a major transformation of our 14 health systems (one for each province and territory plus the federal government). I argue that 3 additional things are essential to build health policy capacity in a healthcare federation such as Canada: (a) A means of "policy governance" that would promote an approach to cooperative federalism in the health arena; (b) The ability to overcome the "policy inertia" resulting from how Canadian Medicare was implemented and subsequently interpreted; and (c) The ability to entertain a long range thinking and planning horizon. My assessment indicates that Canada falls short on each of these items, and the prospects for achieving them are not bright. However, hope springs eternal and it will be interesting to see if the July, 2015 report of the Advisory Panel on Healthcare Innovation manages to galvanize national attention and stimulate concerted action. PMID- 26673651 TI - The Slow, Lingering Death of the English NHS: Comment on "Who Killed the English National Health Service?". AB - The death of the English National Health Service (NHS) may be slow in coming but that does not mean that it is not the Conservative-led UK government's desired end state. The government is displaying tactical cunning in achieving its long term purpose to remould the British state. Powell seeks greater clarity amidst the confusion but the lack of clarity is a principal weapon in the government's assault on the public realm, including the NHS. Moreover, there is ample supporting evidence to caution against Powell's tendency to complacency concerning the ultimate fate of the NHS. PMID- 26673652 TI - Whistleblowing Need not Occur if Internal Voices Are Heard: From Deaf Effect to Hearer Courage: Comment on "Cultures of Silence and Cultures of Voice: The Role of Whistleblowing in Healthcare Organisations". AB - Whistleblowing by health professionals is an infrequent and extraordinary event and need not occur if internal voices are heard. Mannion and Davies' editorial on "Cultures of Silence and Cultures of Voice: The Role of Whistleblowing in Healthcare Organisations" asks the question whether whistleblowing ameliorates or exacerbates the 'deaf effect' prevalent in healthcare organisations. This commentary argues that the focus should remain on internal processes and hearer courage . PMID- 26673653 TI - On Management Matters: Why We Must Improve Public Health Management Through Action: Comment on "Management Matters: A Leverage Point for Health Systems Strengthening in Global Health". AB - Public health management is a pillar of public health practice. Only through effective management can research, theory, and scientific innovation be translated into successful public health action. With this in mind, the U.S. Centers for Disease Control and Prevention (CDC) has developed an innovative program called Improving Public Health Management for Action (IMPACT) which aims to address this critical need by building an effective cadre of public health managers to work alongside scientists to prepare for and respond to disease threats and to effectively implement public health programs. IMPACT is a 2-year, experiential learning program that provides fellows with the management tools and opportunities to apply their new knowledge in the field, all while continuing to serve the Ministry of Health (MoH). IMPACT will launch in 2016 in 2 countries with the intent of expanding to additional countries in future years resulting in a well-trained cadre of public health managers around the world. PMID- 26673654 TI - The Role of Employee Whistleblowing and Raising Concerns in an Organizational Learning Culture - Elusive and Laudable?: Comment on "Cultures of Silence and Cultures of Voice: The Role of Whistleblowing in Healthcare Organisations". AB - It is inevitable that healthcare workers throughout their careers will witness actual or potential threats to patient safety in the course of their work. Some of these threats will result in serious harm occurring to others, whilst at other times such threats will result in minimal harm, or a 'near miss' where harm is avoided at the last minute. Despite organizations encouraging employees to 'speak up' about such threats, healthcare systems globally struggle to engage their staff to do so. Even when staff do raise concerns they are often ignored by those with a responsibility to listen and act. Learning how to create the conditions where employees continuously raise and respond to concerns is essential in creating a continuous and responsive learning culture that cherishes keeping patients and employees safe. Workplace culture is a real barrier to the creation of such a learning system but examples in healthcare exist from which we can learn. PMID- 26673655 TI - What Makes Whistleblowers So Threatening?: Comment on "Cultures of Silence and Cultures of Voice: The Role of Whistleblowing in Healthcare Organisations". AB - Whistleblowing is defined by the retaliation that those who speak out receive. Why some organizations find it almost impossible not to retaliate depends more on the properties of the organization than the act of the individual whistleblower. These properties are, to greater or lesser degree, present in all organizations. Not all organizations retaliate against whistleblowers, but the whistleblower represents a threat to every organization. And to every individual within the organization, because the whistleblower challenges the morality and ethics of the rest of us. PMID- 26673656 TI - Cross-Border Mobility in Italy: Some Considerations in Response to the Recent Commentaries. PMID- 26673657 TI - The Challenge of Complementary and Alternative Medicine After Austerity: A Response to Recent Commentaries. AB - Complementary and Alternative Medicine (CAM) is frequently used in Portugal and it contributes to the improvement of people's health. CAM and Western Medicine (WM) are taken as complements both in the diagnosis and the treatment stage. The Portuguese health system is able to generate certified CAM professionals but the provision of CAM care and services is not included in the national health system. In times of austerity, this is not expected to change and access to CAM care continues to be out-of-pocket health expenditure. But the future for health in Portugal may well involve including CAM therapies in an integrated health system. PMID- 26673658 TI - A uniform porous multilayer-junction thin film for enhanced gas-sensing performance. AB - Highly-uniform In2O3/CuO bilayer and multilayer porous thin films were successfully fabricated using a self-assembled soft template and a simple sputtering deposition technique. The sensor based on the In2O3/CuO bilayer porous thin film shows obviously improved sensing performance to ethanol at a lower working temperature, compared to its single layer counterpart sensors. The response of the In2O3/CuO bilayer sensors exhibit nearly 3 and 5 times higher performance than those of the single layer In2O3 and CuO porous film sensors over the same ethanol concentration, respectively. The sensing mechanism based on the p-n hetero-junction, which contributed to the enhanced sensing performance, was also experimentally confirmed by a control experiment in which an SiO2 insulation layer was inserted between the In2O3 and CuO layers to break the p-n junction. In addition, the sensing performance can be further enhanced by increasing the number of In2O3/CuO junction layers. The facile process can be easily extended to the fabrication of other semiconductor oxide gas sensors for practical sensing applications. PMID- 26673659 TI - Neural Mechanisms for Drosophila Contrast Vision. AB - Spatial contrast, the difference in adjacent luminance values, provides information about objects, textures, and motion and supports diverse visual behaviors. Contrast computation is therefore an essential element of visual processing. The underlying mechanisms, however, are poorly understood. In human psychophysics, contrast illusions are means to explore such computations, but humans offer limited experimental access. Via behavioral experiments in Drosophila, we find that flies are also susceptible to contrast illusions. Using genetic silencing techniques, electrophysiology, and modeling, we systematically dissect the mechanisms and neuronal correlates underlying the behavior. Our results indicate that spatial contrast computation involves lateral inhibition within the same pathway that computes motion of luminance increments (ON pathway). Yet motion-blind flies, in which we silenced downstream motion sensitive neurons needed for optomotor behavior, have fully intact contrast responses. In conclusion, spatial contrast and motion cues are first computed by overlapping neuronal circuits which subsequently feed into parallel visual processing streams. PMID- 26673660 TI - The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane. AB - Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s). The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations), bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions). Bone marrow edema occurs in 68-75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression. PMID- 26673661 TI - Maternal and Perinatal Outcome of Life Threatening Obstetrical Complications Requiring Multiple Transfusions. AB - INTRODUCTION: Obstetrical haemorrhage is the direct cause of maternal mortality, which can be prevented by timely recognition followed by quick and adequate treatment. AIM: To evaluate maternal and perinatal outcome of life threatening obstetric complications requiring multiple transfusions. MATERIALS AND METHODS: It is an observational study conducted on 112 antenatal and postnatal women admitted in a tertiary level hospital, requiring blood and blood products transfusion of >1.5 liters in 24 hours, over a period of 15 months (Aug 2011 to Oct 2012). The demographic and obstetrical profile, amount transfused, mode of delivery, duration of hospital stay, maternal and neonatal morbidity and mortality was evaluated. STATISTICAL ANALYSIS: Statistical analysis of the data was performed using chi-squared test. RESULTS: There were 95 women who presented in antepartum period and 17 in the postpartum. Multigravidas comprised of 70 women, 81 had unsupervised pregnancies and 33 women presented in shock. At admission, 76 peripartum women had severe anaemia and 62 had coagulopathy. Obstetrical hysterectomy was done for 33 women and total 17 women expired. Haemorrhage was the most common indication for transfusion. The mean blood transfusion and volume replacement in 24 hours was 4.2 units & 2.25 liters respectively. The mean hospital stay was 10-15 days. Intra-uterine death at the time of admission was present in 40 women and 72 had live births. After birth, 21 babies required neonatal intensive care, of which 6 expired. CONCLUSION: Antenatal care is important to prevent complications though pregnancy is always unpredictable. Patients' condition at admission is single most important factor often influencing the maternal and perinatal outcome. PMID- 26673662 TI - Survive or die? c-MYC has the last word. PMID- 26673663 TI - Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication. AB - Apoptosis of host cells profoundly influences virus propagation and dissemination, events that are integral to influenza A virus (IAV) pathogenesis. The trigger for activation of apoptosis is regulated by an intricate interplay between cellular and viral proteins, with a strong bearing on IAV replication. Though the knowledge of viral proteins and mechanisms employed by IAV to induce apoptosis has advanced considerably of late, we know relatively little about the repertoire of host factors targeted by viral proteins. Thus, identification of cellular proteins that are hijacked by the virus will help us not only to understand the molecular underpinnings of IAV-induced apoptosis, but also to design future antiviral therapies. Here we show that the nucleoprotein (NP) of IAV directly interacts with and suppresses the expression of API5, a host antiapoptotic protein that antagonizes E2F1-dependent apoptosis. siRNA-mediated depletion of API5, in NP-overexpressed as well as IAV-infected cells, leads to upregulation of apoptotic protease activating factor 1 (APAF1), a downstream modulator of E2F1-mediated apoptosis, and cleavage of caspases 9 and 3, although a reciprocal pattern of these events was observed on ectopic overexpression of API5. In concordance with these observations, annexin V and 7AAD staining assays exhibit downregulation of early and late apoptosis in IAV-infected or NP transfected cells on overexpression of API5. Most significantly, while overexpression of API5 decreases viral titers, cellular NP protein as well as mRNA levels in IAV-infected A549 cells, silencing of API5 expression causes a steep rise in the same parameters. From the data reported in this manuscript, we propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication. PMID- 26673664 TI - Loss of STAT1 protects hair cells from ototoxicity through modulation of STAT3, c Jun, Akt, and autophagy factors. AB - Hair cell damage is a side effect of cisplatin and aminoglycoside use. The inhibition or attenuation of this process is a target of many investigations. There is growing evidence that STAT1 deficiency decreases cisplatin-mediated ototoxicity; however, the role of STAT function and the molecules that act in gentamicin-mediated toxicity have not been fully elucidated. We used mice lacking STAT1 to investigate the effect of STAT1 ablation in cultured organs treated with cisplatin and gentamicin. Here we show that ablation of STAT1 decreased cisplatin toxicity and attenuated gentamicin-mediated hair cell damage. More TUNEL-positive hair cells were observed in explants of wild-type mice than that of STAT1(-/-) mice. Although cisplatin increased serine phosphorylation of STAT1 in wild-type mice and diminished STAT3 expression in wild-type and STAT1(-/-) mice, gentamicin increased tyrosine phosphorylation of STAT3 in STAT1(-/-) mice. The early inflammatory response was manifested in the upregulation of TNF-alpha and IL-6 in cisplatin-treated explants of wild-type and STAT1(-/-) mice. Expression of the anti-inflammatory cytokine IL-10 was altered in cisplatin-treated explants, upregulated in wild-type explants, and downregulated in STAT1(-/-) explants. Cisplatin and gentamicin triggered the activation of c-Jun. Activation of Akt was observed in gentamicin-treated explants from STAT1(-/-) mice. Increased levels of the autophagy proteins Beclin-1 and LC3-II were observed in STAT1(-/-) explants. These data suggest that STAT1 is a central player in mediating ototoxicity. Gentamicin and cisplatin activate different downstream factors to trigger ototoxicity. Although cisplatin and gentamicin triggered inflammation and activated apoptotic factors, the absence of STAT1 allowed the cells to overcome the effects of these drugs. PMID- 26673665 TI - Effects of PI3K inhibitor NVP-BKM120 on overcoming drug resistance and eliminating cancer stem cells in human breast cancer cells. AB - The multidrug resistance (MDR) phenotype often accompanies activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which renders a survival signal to withstand cytotoxic anticancer drugs and enhances cancer stem cell (CSC) characteristics. As a result, PI3K/AKT-blocking approaches have been proposed as antineoplastic strategies, and inhibitors of PI3K/AKT are currently being trailed clinically in breast cancer patients. However, the effects of PI3K inhibitors on MDR breast cancers have not yet been elucidated. In the present study, the tumorigenic properties of three MDR breast cancer cell lines to a selective inhibitor of PI3K, NVP-BKM120 (BKM120), were assessed. We found that BKM120 showed a significant cytotoxic activity on MDR breast cancer cells both in vitro and in vivo. When doxorubicin (DOX) was combined with BKM120, strong synergistic antiproliferative effect was observed. BKM120 activity induced the blockage of PI3K/AKT signaling and NF-kappaB expression, which in turn led to activate caspase-3/7 and caspase-9 and changed the expression of several apoptosis-related gene expression. Furthermore, BKM120 effectively eliminated CSC subpopulation and reduced sphere formation of these drug-resistant cells. Our findings indicate that BKM120 partially overcomes the MDR phenotype in chemoresistant breast cancer through cell apoptosis induction and CSC abolishing, which appears to be mediated by the inhibition of the PI3K/AKT/NF-kappaB axis. This offers a strong rationale to explore the therapeutic strategy of using BKM120 alone or in combination for chemotherapy-nonresponsive breast cancer patients. PMID- 26673667 TI - Endosulfan induces male infertility. PMID- 26673666 TI - Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways. AB - Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke. PMID- 26673668 TI - Cellular prion protein promotes post-ischemic neuronal survival, angioneurogenesis and enhances neural progenitor cell homing via proteasome inhibition. AB - Although cellular prion protein (PrP(c)) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To elucidate the role of PrP(c) in post-ischemic brain remodeling, we herein exposed PrP(c) wild type (WT), PrP(c) knockout (PrP-/-) and PrP(c) overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP-/- mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP-/- mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP-/ , indicating that proteasome inhibition mediates the neuroprotective effects of PrP(c). Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1alpha and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrP(c) on intracerebral NPC homing, we intravenously infused GFP(+) NPCs in ischemic WT, PrP-/- and PrP+/+ mice, showing that brain accumulation of GFP(+) NPCs was greatly reduced in PrP-/- mice, but increased in PrP+/+ animals. Our results suggest that PrP(c) induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity. PMID- 26673670 TI - Giant Cell Lesions of Lungs: A Histopathological and Morphometric Study of Seven Autopsy Cases. AB - INTRODUCTION: Macrophages undergo fusion to form multinucleated giant cells (MGC) in several pathologic conditions. The exact mechanism of their generation is still unclear. MGC are a common feature of granulomas that develop during various inflammatory reactions. AIM: To study the histopathological features of giant cell lesions in lungs and correlate the characteristics of giant cells with other histopathological findings. Also, to determine the utility of morphometry to differentiate foreign body and Langhans MGC. MATERIALS AND METHODS: Seven cases were analysed. Specimen of lungs was grossed, sectioned and processed. Routinely, tissue sections were stained by Haematoxylin and Eosin (H&E) stain. Polarizing microscopy and special stains were employed in selected cases. Granulomas and MGC were counted and measured. Several other parameters like location, distribution, type and number of MGC, associated predominant inflammatory component and nature of granulomas were analysed. RESULTS: Five patterns of lesions were observed in seven cases. Aspiration pneumonia was seen in three cases (42.85%) and constituted the most common pattern. However, aspiration pneumonia as the only cause of MGC was seen in only one case (14.28%). Pulmonary tuberculosis and asteroid bodies constituted two cases (28.57%) each. Cryptococcal pneumonia and cholesterol clefts constituted one case (14.28%) each. Crypococci were demonstrated to be positively birefringent by polarized microscopy on Ziehl Neelsen stained sections. Based on statistical analysis of morphometric data, a new index (NP index) was proposed to statistically categorize MGC into foreign body type and Langhans type. NP index value of <=0.016 was found to be statistically significant (p<0.005) in foreign body MGC. It had high sensitivity and efficacy. CONCLUSION: MGC may not be always associated with granulomas. The mechanisms that lead to the occurrence of MGC, independent of granuloma needs to be elucidated. Morphometry may serve as a useful aid. But a pathologist has to rely on the morphological details to categorize MGC. PMID- 26673669 TI - TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes. AB - Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult. PMID- 26673671 TI - CpG promoter methylation status is not a prognostic indicator of gene expression in beryllium challenge. AB - Individuals exposed to beryllium (Be) may develop Be sensitization (BeS) and progress to chronic beryllium disease (CBD). Recent studies with other metal antigens suggest epigenetic mechanisms may be involved in inflammatory disease processes, including granulomatous lung disorders and that a number of metal cations alter gene methylation. The objective of this study was to determine if Be can exert an epigenetic effect on gene expression by altering methylation in the promoter region of specific genes known to be involved in Be antigen-mediated gene expression. To investigate this objective, three macrophage tumor mouse cell lines known to differentially produce tumor necrosis factor (TNF)-alpha, but not interferon (IFN)-gamma, in response to Be antigen were cultured with Be or controls. Following challenges, ELISA were performed to quantify induced TNFalpha and IFNgamma expression. Bisulfate-converted DNA was evaluated by pyrosequencing to quantify CpG methylation within the promoters of TNFalpha and IFNgamma. Be challenged H36.12J cells expressed higher levels of TNFalpha compared to either H36.12E cells or P388D.1 cells. However, there were no variations in TNFalpha promoter CpG methylation levels between cell lines at the six CpG sites tested. H36.12J cell TNFalpha expression was shown to be metal-specific by the induction of significantly more TNFalpha when exposed to Be than when exposed to aluminum sulfate, or nickel (II) chloride, but not when exposed to cobalt (II) chloride. However, H36.12J cell methylation levels at the six CpG sites examined in the TNFalpha promoter did not correlate with cytokine expression differences. Nonetheless, all three cell lines had significantly more promoter methylation at the six CpG sites investigated within the IFNgamma promoter (a gene that is not expressed) when compared to the six CpG sites investigated in the TNFalpha promoter, regardless of treatment condition (p < 1.17 * 10(-9)). These findings suggest that, in this cell system, promoter hypo-methylation may be necessary to allow expression of metal-induced TNFalpha and that promoter hyper-methylation in the IFNgamma promoter may interfere with expression. Also, at the dozen CpG sites investigated in the promoter regions of both genes, beryllium had no impact on promoter methylation status, despite its ability to induce pro-inflammatory cytokine expression. PMID- 26673672 TI - Intracranial blastomycotic abscess mimicking malignant brain neoplasm: Successful treatment with voriconazole and surgery. AB - BACKGROUND: Cerebral blastomycosis is a rarely reported disease, and in the absence of associated, underlying systemic infection, poses a great diagnostic difficulty. Magnetic resonance imaging can sometimes provide equivocal information when trying to pinpoint a diagnosis. Classically, cerebral blastomycosis has been treated with amphotericin B. Voriconazole is a newer triazole antifungal with potential as a follow-up treatment of blastomycosis of the central nervous system after initial therapy with amphotericin B. CASE DESCRIPTION: We describe one such case of a cerebral blastomycotic abscess, presenting in the absence of any systemic disease, which was initially thought to be a neoplasm. It was successfully treated by surgical resection followed by sequential amphotericin B and voriconazole. The patient did well with voriconazole therapy and was followed for voriconazole tolerance with liver function tests, which continued to be stable at 8 months past the initiation of therapy. At 12 months postoperatively, the patient was doing well and showed gradual improvement in a visual field cut, with no sign of recurrent infection. CONCLUSIONS: Isolated cerebral blastomycosis can present a diagnostic challenge. In the absence of systemic infection, surgical resection followed by antifungal therapy is a logical treatment plan. PMID- 26673673 TI - Characterization of Melon necrotic spot virus Occurring on Watermelon in Korea. AB - Melon necrotic spot virus (MNSV) was recently identified on watermelon (Citrullus vulgaris) in Korea, displaying as large necrotic spots and vein necrosis on the leaves and stems. The average occurrence of MNSV on watermelon was found to be 30 65% in Hapcheon and Andong City, respectively. Four isolates of the virus (MNSV HW, MNSV-AW, MNSV-YW, and MNSV-SW) obtained from watermelon plants in different areas were non-pathogenic on ten general indicator plants, including Chenopodium quinoa, while they infected systemically six varieties of Cucurbitaceae. The virus particles purified by 10-40% sucrose density gradient centrifugation had a typical ultraviolet spectrum, with a minimum at 245 nm and a maximum at 260 nm. The morphology of the virus was spherical with a diameter of 28-30 nm. Virus particles were observed scattered throughout the cytoplasm of watermelon cells, but no crystals were detected. An ELISA was conducted using antiserum against MNSV-HW; the optimum concentrations of IgG and conjugated IgG for the assay were 1 MUl/ml and a 1:8,000-1:10,000 dilutions, respectively. Antiserum against MNSV HW could capture specifically both MNSV-MN from melon and MNSV-HW from watermelon by IC/RT-PCR, and they were effectively detected with the same specific primer to produce product of 1,172 bp. The dsRNA of MNSV-HW had the same profile (4.5, 1.8, and 1.6 kb) as that of MNSV-MN from melon. The nucleotide sequence of the coat protein of MNSV-HW gave a different phylogenetic tree, having 17.2% difference in nucleotide sequence compared with MNSV isolates from melon. PMID- 26673674 TI - Social and Medical Determinants of Cardiometabolic Health: The Big Picture. AB - Cardiometabolic diseases, including diabetes and heart disease, account for >12 million years of life lost annually among Black adults in the United States. Health disparities are geographically localized, with ~80% of health disparities occurring within ~6000 (16%) of all 38,000 US ZIP codes. Socio-economic status (SES), behavioral and environmental factors (social determinants) account for ~80% of variance in health outcomes and cluster geographically. Neighborhood SES is inversely associated with prevalent diabetes and hypertension, and Blacks are four times more likely than Whites to live in lowest SES neighborhoods. In ZIP code 48235 (Detroit, 97% Black, 16.2% unemployed, income/capita $18,343, 23.6% poverty), 1082 Medicare fee-for service (FFS) beneficiaries received care for type 2 diabetes (T2D) and coronary artery disease (CAD) in 2012. Collectively, these beneficiaries had 1082 inpatient admissions and 839 emergency department visits, mean cost $27,759/beneficiary and mortality 2.7%. Nationally in 2011, 236,222 Black Medicare FFS beneficiaries had 213,715 inpatient admissions, 191,346 emergency department visits, mean cost $25,580/beneficiary and 2.4% mortality. In addition to more prevalent hypertension and T2D, Blacks appear more susceptible to clinical complications of risk factors than Whites, including hypertension as a contributor to stroke. Cardiometabolic health equity in African Americans requires interventions on social determinants to reduce excess risk prevalence of risk factors. Social-medical interventions to promote timely access to, delivery of and adherence with evidence-based medicine are needed to counterbalance greater disease susceptibility. Place-based interventions on social and medical determinants of health could reduce the burden of life lost to cardiometabolic diseases in Blacks. PMID- 26673675 TI - Diagnosis and treatment of pancreatic pseudocysts and cystic tumors based on own material and quoted literature. AB - Pseudocysts constitute the most basic cystic lesions of the pancreas. Symptomatic cysts may be treated by means of both minimally invasive methods and surgery. Currently, it is believed that approximately 5% of cystic lesions in the pancreas may in fact, be neoplastic cystic tumors. Their presence is manifested by generally irregular multilocular structures, solid nodules inside the cyst or in the pancreatic duct, frequently vascularized, as well as fragmentary thickening of the cystic wall or septation. AIM: The aim of this paper was to present current management, both diagnostic and therapeutic, in patients with pancreatic pseudocysts and cystic tumors. The article has been written based on the material collected and prepared in the author's Department as well as on the basis of current reports found in the quoted literature. MATERIAL AND METHODS RESULTS: In 2000-2012, the Second Department of General, Gastrointestinal and Oncological Surgery of the Alimentary Tract treated 179 patients with cystic lesions in the region of the pancreas. This group comprised 12 cases of cystic tumors and 167 pseudocysts. Twenty-three patients (13.8%) were monitored only and 144 received procedural treatment. Out of the latter group, 75 patients underwent drainage procedures and 48 were qualified to endoscopic cystogastrostomy or cystoduodenostomy. The endoscopic procedure was unsuccessful in 11 cases (23%). In a group of patients with a pancreatic cystic tumor (12 patients), 6 of them (50%) underwent therapeutic resection of the tumor with adequate fragment of the gland. CONCLUSIONS: Endoscopic drainage is an effective and safe method of minimally invasive treatment of pancreatic cysts. The patients who do not qualify to endoscopic procedures require surgical treatment. The differentiation of a neoplasm from a typical cyst is of fundamental significance for the selection of the treatment method. PMID- 26673676 TI - Pulmonary Fibrosis Foundation Summit 2015. PMID- 26673677 TI - Giant barocaloric effect in hexagonal Ni2In-type Mn-Co-Ge-In compounds around room temperature. AB - The most widespread cooling techniques based on gas compression/expansion encounter environmental problems. Thus, tremendous effort has been dedicated to develop alternative cooling technique and search for solid state materials that show large caloric effects. An application of pressure to a material can cause a change in temperature, which is called the barocaloric effect. Here we report the giant barocaloric effect in a hexagonal Ni2In-type MnCoGe0.99In0.01 compound involving magnetostructural transformation, Tmstr, which is accompanied with a big difference in the internal energy due to a great negative lattice expansion(DeltaV/V ~ 3.9%). High resolution neutron diffraction experiments reveal that the hydrostatic pressure can push the Tmstr to a lower temperature at a rate of 7.7 K/kbar, resulting in a giant barocaloric effect. The entropy change under a moderate pressure of 3 kbar reaches 52 J kg(-1) K(-1), which exceeds that of most materials, including the reported giant magnetocaloric effect driven by 5 T magnetic field that is available only by superconducting magnets. PMID- 26673678 TI - Ultrasonography of the tongue in macroglossia - a case report. AB - This paper is an attempt to assess the usefulness of ultrasonography in the diagnosis of the enlargement of the tongue (macroglossia). The role of sonography in diagnosing local pathologies of the tongue, such as neoplasms, abscesses or granulomas, has been well-established for 20 years. Rarely is its usefulness considered with respect to diagnosing macroglossia with concomitant systemic diseases. The starting point of these considerations was the presented case of a 59-year-old patient with considerably enlarged tongue. The patient had difficulty speaking and ingesting meals. Moreover, he complained about swelling and pain in the carpal and proximal interphalangeal joints. Tongue ultrasound examination revealed blurred lingual structure with evident, irregular vascular pattern in the color Doppler. The obtained image helped to rule out local pathology of the tongue and directed our diagnostic considerations towards immunoglobulin-related diseases (deposition diseases). We believe that the presented ultrasound image of the tongue was helpful in the diagnostic process. Establishing the final, correct diagnosis was a particularly strenuous process. The suspicion of a deposition disease had been rejected during two previous stays in two hospitals. This was the consequence of a negative diagnostic test of staining tissue deposits with Congo red. An accurate diagnosis occurred to be a rare form of a deposition disease: lambda light chain disease with symptoms of amyloidosis. Such a diagnosis was based on a thorough hematological analysis. A high level of free lambda light chains in the serum was detected and the bone marrow biopsy showed 13% of plasma cells. The patient underwent chemotherapy. PMID- 26673679 TI - Identification of a highly efficient stationary phase promoter in Bacillus subtilis. AB - A promoter that enabled high-level expression of the target gene during the stationary phase in the absence of an inducer would facilitate the efficient production of heterogeneous proteins at a low cost. In this study, a genome-scale microarray-based approach was employed to identify promoters that induced high level expression of the target genes in Bacillus subtilis from the late log phase to the stationary phase without an inducer. Eleven candidate promoters were selected based on B. subtilis microarray data and the quantitative PCR analysis. Among the selected promoters, Pylb exhibited the highest activity with the reporter bgaB during the stationary phase. Compared with P43 (a commonly used constitutive promoter), promoter Pylb could express two reporter genes (egfp and mApple), and the expression levels of EGFP and RFP were 7.8- and 11.3-fold higher than that of P43, respectively. This finding was verified by overexpression of the genes encoding pullulanase and organophosphorus hydrolase, the activities of which were 7.4- and 2.3-fold higher, respectively, when driven by Pylb compared with P43. Therefore, our results suggest that the Pylb promoter could be used to overexpress target genes without an inducer; this method could facilitate the identification and evaluation of attractive promoters in the genome. PMID- 26673680 TI - Type 2 Diabetes Mellitus and the Association of Candidate Genes in Asian Indian Population from Hyderabad, India. AB - INTRODUCTION: Genetic and environmental factors play an important role in susceptibility to type 2 diabetes mellitus (T2DM). Several genes have been implicated in the development of T2DM. Genetic variants of candidate genes are, therefore, prime targets for molecular analysis. AIM: In this study, we have selected 3 candidate genes, namely, TCF7L2, SLC30A8, and IGF2, for assessing their association with T2DM in an Indian population. MATERIALS AND METHODS: Five hundred individuals were enrolled in this case-control study- 250 T2DM patients and 250 healthy control individuals. Clinical characteristics were obtained for all subjects, and genotype analysis was performed by PCR-RFLP analysis. RESULTS: Allele and genotyping frequencies, odds ratios, and 95% confidence intervals were calculated for 3 single nucleotide polymorphisms (SNPs), 1 each from TCF7L2 (rs7903146), SLC30A8 (rs13266634), and IGF2 (rs680) in T2DM patients. The rs7903146 and rs680 polymorphisms were found to be significantly associated with T2DM (p < 0.05), whereas the rs13266634 polymorphism was not (p > 0.05). The multifactor dimensionality reduction method identified the particular polymorphisms associated with an increased risk of disease. CONCLUSION: The present study indicated that the gene-gene interaction model successfully predicted T2DM risk based on TCF7L2 and SLC30A8 polymorphisms. These results provide strong evidence of independent association between T2DM and the 3 SNPs analysed herein. PMID- 26673681 TI - Heart-type fatty acid binding protein and high-sensitivity troponin T are myocardial damage markers that could predict adverse clinical outcomes in patients with peripheral artery disease. AB - BACKGROUND: Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators of future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD. METHODS AND RESULTS: We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow-up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors. CONCLUSION: The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients. PMID- 26673682 TI - First-principles anharmonic quantum calculations for peptide spectroscopy: VSCF calculations and comparison with experiments. AB - First-principles quantum calculations for anharmonic vibrational spectroscopy of three protected dipeptides are carried out and compared with experimental data. Using hybrid HF/MP2 potentials, the Vibrational Self-Consistent Field with Second Order Perturbation Correction (VSCF-PT2) algorithm is used to compute the spectra without any ad hoc scaling or fitting. All of the vibrational modes (135 for the largest system) are treated quantum mechanically and anharmonically using full pair-wise coupling potentials to represent the interaction between different modes. In the hybrid potential scheme the MP2 method is used for the harmonic part of the potential and a modified HF method is used for the anharmonic part. The overall agreement between computed spectra and experiment is very good and reveals different signatures for different conformers. This study shows that first-principles spectroscopic calculations of good accuracy are possible for dipeptides hence it opens possibilities for determination of dipeptide conformer structures by comparison of spectroscopic calculations with experiment. PMID- 26673683 TI - EFFECT OF RESTRICTED HIP FLEXOR MUSCLE LENGTH ON HIP EXTENSOR MUSCLE ACTIVITY AND LOWER EXTREMITY BIOMECHANICS IN COLLEGE-AGED FEMALE SOCCER PLAYERS. AB - BACKGROUND: Hip flexor tightness is theorized to alter antagonist muscle function through reciprocal inhibition and synergistic dominance mechanisms. Synergistic dominance may result in altered movement patterns and increased risk of lower extremity injury. HYPOTHESIS/PURPOSE: To compare hip extensor muscle activation, internal hip and knee extension moments during double-leg squatting, and gluteus maximus strength in those with and without clinically restricted hip flexor muscle length. DESIGN: Causal-comparative cross-sectional laboratory study. METHOD: Using a modified Thomas Test, female soccer athletes were assigned to a restricted (>0 degrees of sagittal plane hip motion above the horizontal; n=20, age=19.9 +/- 1 years, ht=167.1 +/- 6.4 cm, mass=64.7 +/- 8.2kg) or normal (>15 degrees of sagittal plane hip motion below horizontal; n=20, age=19.4 +/- 1 years, ht=167.2 +/- 5.5 cm, mass=61.2 +/- 8.6 kg) hip flexor muscle length group. Surface electromyographic (sEMG) activity of the gluteus maximus and biceps femoris, and net internal hip and knee extension moments were measured between groups during a double-leg squat. Isometric gluteus maximus strength was assessed using handheld dynamometry. RESULTS: Individuals with restricted hip flexor muscle length demonstrated less gluteus maximus activation (p=0.008) and a lower gluteus maximus : biceps femoris co-activation ratio (p=0.004). There were no significant differences (p>0.05) in hip or knee extension moments, isometric gluteus maximus strength, or biceps femoris activation between groups. CONCLUSIONS: Female soccer athletes with hip flexor muscle tightness exhibit less gluteus maximus activation and lower gluteus maximus : biceps femoris co activation while producing similar net hip and knee extension moments. Thus, individuals with hip flexor muscle tightness appear to utilize different neuromuscular strategies to control lower extremity motion. LEVEL OF EVIDENCE: 3. PMID- 26673684 TI - Identification of Key Proteins in Human Epithelial Cells Responding to Bystander Signals From Irradiated Trout Skin. AB - Radiation-induced bystander signaling has been found to occur in live rainbow trout fish (Oncorhynchus mykiss). This article reports identification of key proteomic changes in a bystander reporter cell line (HaCaT) grown in low-dose irradiated tissue-conditioned media (ITCM) from rainbow trout fish. In vitro explant cultures were generated from the skin of fish previously exposed to low doses (0.1 and 0.5 Gy) of X-ray radiation in vivo. The ITCM was harvested from all donor explant cultures and placed on recipient HaCaT cells to observe any change in protein expression caused by the bystander signals. Proteomic methods using 2-dimensional (2D) gel electrophoresis and mass spectroscopy were employed to screen for novel proteins expressed. The proteomic changes measured in HaCaT cells receiving the ITCM revealed that exposure to 0.5 Gy induced an upregulation of annexin A2 and cingulin and a downregulation of Rho-GDI2, F-actin-capping protein subunit beta, microtubule-associated protein RP/EB family member, and 14 3-3 proteins. The 0.1 Gy dose also induced a downregulation of Rho-GDI2, hMMS19, F-actin-capping protein subunit beta, and microtubule-associated protein RP/EB family member proteins. The proteins reported may influence apoptotic signaling, as the results were suggestive of an induction of cell communication, repair mechanisms, and dysregulation of growth signals. PMID- 26673685 TI - Dearomatization of Indoles via Palladium-Catalyzed Allylic C-H Activation. AB - The first Pd-catalyzed allylic dearomatization of substituted indoles triggered by C-H bond activation is reported. The presence of a catalytic amount of 2,5 DMBQ is proven to be a key factor for the high yield. This one-pot tandem allylic C-H activation/dearomatization sequence provides a straightforward access to 3,3 disubstituted indolines. PMID- 26673686 TI - Attachment in middle childhood: predictors, correlates, and implications for adaptation. AB - Middle childhood is a relative lacuna in behavioral attachment research. We examined antecedents, correlates, and implications of parent-child attachment at age 10 in a longitudinal study of community families from a Midwestern US state (N = 102, mothers, fathers, and children). Dimensions of security, avoidance, ambivalence, and disorganization of children's attachment to each parent were observed in lengthy naturalistic interactions and assessed using Iowa Attachment Behavioral Coding (IABC). IABC scores were meaningfully associated with history of parental responsiveness (7-80 months) and with earlier and concurrent attachment security, assessed with other established instruments (parent- and observer-rated Attachment Q-Set at 25 months, children's reports at age 8 and 10). Structural equation modeling analyses revealed that the overall history of responsive care was meaningfully associated with Security, Avoidance, and Disorganization at age 10, in both mother-child and father-child relationships, and that most recent care uniquely predicted Security. IABC scores were also meaningfully related to a broad range of measures of child adaptation at ages 10 12. Cumulative history of children's security from infancy to middle childhood, integrating measures across relationships and methodologies, also predicted child adaptation at ages 10-12. PMID- 26673687 TI - Bio-Friendly Alternatives for Xylene - Carrot oil, Olive oil, Pine oil, Rose oil. AB - BACKGROUND: Xylene is a flammable liquid with characteristic petroleum or aromatic odours, it is miscible with most of the organic solvents and paraffin wax. Xylene clears tissues rapidly and renders transparency, facilitating clearing endpoint determination, this made it to be used as a clearing agent in routine histopathological techniques. Even though it is a good clearing agent, it causes damage to the tissues by its hardening effect particularly those fixed in non-protein coagulant fixatives. Apart from these tissue effects, it has severe, long lasting ill effects on health of technicians and pathologists when exposed to longer duration. Hence in order to overcome these effects and replace xylene with a safe alternative agent, the present study was carried out to assess the clearing ability and bio-friendly nature of four different natural oils i.e., Carrot oil, Olive oil, Pine oil and Rose oil in comparison with that of Xylene. According to Bernoulli's principle of fluid dynamics, to decrease viscosity of these oils and increase penetration into tissues for rapid clearing hot-air oven technique was used. AIMS: To assess:1) Clearing ability and bio-friendly nature of four different oils i.e., Carrot oil, Olive oil, Pine oil, Rose oil in comparison with that of xylene, 2) Application of Bernoulli's principle of fluid dynamics in rapid clearing of tissues by using hot-air oven. MATERIALS AND METHODS: Forty different formalin fixed tissue samples were taken. Each sample of tissue was cut into 5 bits (40x5=200 total bits) which were subjected for dehydration in differential alcohol gradients. Later, each bit is kept in 4 different oils such as Carrot oil, Olive oil, Pine oil, Rose oil and xylene and transferred into hot-air oven. Further routine steps of processing, sectioning and staining were done. Individual sections cleared in four different oils were assessed for cellular architecture, staining quality and a comparison was done between them. RESULTS: Results showed that all the four oils had ability to clear the tissues similar to that of xylene. Pine oil was superior in its physical and clearing properties, which also maintained good cellular architecture and distinct staining quality, when compared with other oils and xylene. CONCLUSION: Carrot oil, Olive oil, Pine oil, Rose oil, are not only bio friendly and economical but can also be used as clearing agent instead of xylene. In this study stability and longetivity of haematoxyllin and eosin staining was evaluated for over a period of one year and no significant difference in staining quality were observed. PMID- 26673688 TI - Feasibility of a Randomized Clinical Trial for Treatment of Femoroacetabular Impingement of the Hip. AB - BACKGROUND: Symptomatic femoroacetabular impingement (FAI) is currently corrected by surgery. However, it is possible that nonsurgical treatment could resolve symptomatic FAI in some patients; thus, uncertainty about the necessity of surgical treatment exists. The current equipoise concerning FAI treatment presents an opportunity to conduct a randomized controlled trial (RCT) of surgical and nonsurgical treatment options. Given the unique challenge of adequate patient enrollment in RCTs, it is important that a preliminary study is done to appraise the feasibility of conducting an RCT. PURPOSE: To estimate enrollment rates of a planned future RCT to compare surgical and nonsurgical treatments for symptomatic FAI and to identify factors associated with patients' willingness to participate in the randomized trial. STUDY DESIGN: Cross-sectional study; Level of evidence, 4. METHODS: Patients diagnosed with FAI at 2 orthopaedic centers were presented with a hypothetical randomized trial comparing 2 treatment options for FAI. All patients completed forms providing information regarding their willingness to participate and treatment preferences. RESULTS: A total of 75 patients participated in the study: 53 and 22 from 2 centers, respectively. Twenty-eight percent indicated absolute willingness to participate in the trial, 40% were probably willing or unsure, and 32% were definitely not willing; 18.7% had a strong preference for surgery while 2.7% strongly preferred nonsurgical treatment. The majority (78.6%) had no strong preference for either treatment arm. There were correlations between treatment preferences and willingness to participate. Patients with a strong treatment preference and/or a preference for surgery were less likely to be willing to participate. CONCLUSION: The study findings suggest that sufficient patient accrual for a randomized trial of FAI treatment is currently feasible while equipoise still exists among patients and surgeons. PMID- 26673689 TI - An Anomalous Right Subclavian Artery with a Retrotracheal Course: A Case Report. AB - An aberrant right subclavian artery arising as the last vessel of the arch of aorta is an uncommon anatomic anomaly with prevalence reported between 0.2% and 2.0%. In 80% of the cases the aberrant right subclavian artery takes a retro oesophageal course to the right upper limb. During routine dissection of cadavers for teaching undergraduate medical students an anomalous retrotracheal right subclavian artery which is a very rare vascular anomaly was encountered in a 35 year-old male cadaver. The artery arose as the last branch of the arch of aorta and coursed to the right between the trachea and oesophagus. The presence of this vascular anomaly could be an unusual cause of dysphagia and breathing difficulty. The clinical significance and embryological aspects of this vascular variant is discussed in this paper. PMID- 26673690 TI - Be a thought leader. PMID- 26673691 TI - Decreasing workplace incivility. PMID- 26673692 TI - Ganglioside Intake Increases Plasma Ganglioside Content in Human Participants. AB - BACKGROUND: Preclinical studies reveal associations between intestinal ganglioside content and inflammatory bowel disease (IBD). Since a low level of ganglioside is associated with higher production of proinflammatory signals in the intestine, it is important to determine safety and bioavailability of dietary ganglioside for application as a potential therapeutic agent. MATERIALS AND METHODS: Healthy volunteers (HVs; n = 18) completed an 8-week supplementation study to demonstrate safety and bioavailabity of ganglioside consumption. HVs were randomized to consume a milk fat fraction containing 43 mg/d ganglioside or placebo, and patients with IBD (n = 5) consumed ganglioside supplement in a small pilot study. Plasma gangliosides were characterized using reverse-phase liquid chromatography-QQQ mass spectrometry. Intestinal permeability was assessed by oral lactulose/mannitol, and quality of life was assessed by quality of life in the IBD questionnaire. RESULTS: There were no adverse events associated with dietary ganglioside intake. Ganglioside consumption increased ( P < .05) plasma content of total GD3 by 35% over 8 weeks. HVs consuming ganglioside exhibited a 19% decrease in intestinal permeability ( P = .04). Consumption of ganglioside was associated with a 39% increase ( P < .01) in emotional health and a 36% improvement ( P < .02) in systemic symptoms in patients with IBD. CONCLUSION: Impaired intestinal integrity characteristic of IBD results in increased permeability to bacterial antigens and decreased nutrient absorption. Intestinal integrity may be improved by dietary treatment with specific species of ganglioside. Ganglioside is a safe, bioavailable dietary compound that can be consumed to potentially improve quality of life in patients with IBD and treat other disorders involving altered ganglioside metabolism. This study was registered at clinicaltrials.gov as NCT02139709. PMID- 26673694 TI - GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. AB - Transfer RNAs represent the largest, most ubiquitous class of non-protein coding RNA genes found in all living organisms. The tRNAscan-SE search tool has become the de facto standard for annotating tRNA genes in genomes, and the Genomic tRNA Database (GtRNAdb) was created as a portal for interactive exploration of these gene predictions. Since its published description in 2009, the GtRNAdb has steadily grown in content, and remains the most commonly cited web-based source of tRNA gene information. In this update, we describe not only a major increase in the number of tRNA predictions (>367000) and genomes analyzed (>4370), but more importantly, the integration of new analytic and functional data to improve the quality and biological context of tRNA gene predictions. New information drawn from other sources includes tRNA modification data, epigenetic data, single nucleotide polymorphisms, gene expression and evolutionary conservation. A richer set of analytic data is also presented, including better tRNA functional prediction, non-canonical features, predicted structural impacts from sequence variants and minimum free energy structural predictions. Views of tRNA genes in genomic context are provided via direct links to the UCSC genome browsers. The database can be searched by sequence or gene features, and is available at http://gtrnadb.ucsc.edu/. PMID- 26673693 TI - Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation. AB - Ets1 is a sequence-specific transcription factor that plays an important role during hematopoiesis, and is essential for the transition of CD4(-)/CD8(-) double negative (DN) to CD4(+)/CD8(+) double positive (DP) thymocytes. Using genome-wide and functional approaches, we investigated the binding properties, transcriptional role and chromatin environment of Ets1 during this transition. We found that while Ets1 binding at distal sites was associated with active genes at both DN and DP stages, its enhancer activity was attained at the DP stage, as reflected by levels of the core transcriptional hallmarks H3K4me1/3, RNA Polymerase II and eRNA. This dual, stage-specific ability reflected a switch from non-T hematopoietic toward T-cell specific gene expression programs during the DN to-DP transition, as indicated by transcriptome analyses of Ets1(-/-) thymic cells. Coincidentally, Ets1 associates more specifically with Runx1 in DN and with TCF1 in DP cells. We also provide evidence that Ets1 predominantly binds distal nucleosome-occupied regions in DN and nucleosome-depleted regions in DP. Finally and importantly, we demonstrate that Ets1 induces chromatin remodeling by displacing H3K4me1-marked nucleosomes. Our results thus provide an original model whereby the ability of a transcription factor to bind nucleosomal DNA changes during differentiation with consequences on its cognate enhancer activity. PMID- 26673695 TI - MMB-GUI: a fast morphing method demonstrates a possible ribosomal tRNA translocation trajectory. AB - Easy-to-use macromolecular viewers, such as UCSF Chimera, are a standard tool in structural biology. They allow rendering and performing geometric operations on large complexes, such as viruses and ribosomes. Dynamical simulation codes enable modeling of conformational changes, but may require considerable time and many CPUs. There is an unmet demand from structural and molecular biologists for software in the middle ground, which would allow visualization combined with quick and interactive modeling of conformational changes, even of large complexes. This motivates MMB-GUI. MMB uses an internal-coordinate, multiscale approach, yielding as much as a 2000-fold speedup over conventional simulation methods. We use Chimera as an interactive graphical interface to control MMB. We show how this can be used for morphing of macromolecules that can be heterogeneous in biopolymer type, sequence, and chain count, accurately recapitulating structural intermediates. We use MMB-GUI to create a possible trajectory of EF-G mediated gate-passing translocation in the ribosome, with all atom structures. This shows that the GUI makes modeling of large macromolecules accessible to a wide audience. The morph highlights similarities in tRNA conformational changes as tRNA translocates from A to P and from P to E sites and suggests that tRNA flexibility is critical for translocation completion. PMID- 26673696 TI - Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases. AB - MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer. PMID- 26673697 TI - Circularization pathway of a bacterial group II intron. AB - Group II introns are large RNA enzymes that can excise as lariats, circles or in a linear form through branching, circularization or hydrolysis, respectively. Branching is by far the main and most studied splicing pathway while circularization was mostly overlooked. We previously showed that removal of the branch point A residue from Ll.LtrB, the group II intron from Lactococcus lactis, exclusively leads to circularization. However, the majority of the released intron circles harbored an additional C residue of unknown origin at the splice junction. Here, we exploited the Ll.LtrB-DeltaA mutant to study the circularization pathway of bacterial group II introns in vivo. We demonstrated that the non-encoded C residue, present at the intron circle splice junction, corresponds to the first nt of exon 2. Intron circularization intermediates, harboring the first 2 or 3 nts of exon 2, were found to accumulate showing that branch point removal leads to 3' splice site misrecognition. Traces of properly ligated exons were also detected functionally confirming that a small proportion of Ll.LtrB-DeltaA circularizes accurately. Overall, our data provide the first detailed molecular analysis of the group II intron circularization pathway and suggests that circularization is a conserved splicing pathway in bacteria. PMID- 26673698 TI - Transcriptional, post-transcriptional and chromatin-associated regulation of pri miRNAs, pre-miRNAs and moRNAs. AB - MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation. Our understanding about the transcriptional regulation of miRNA genes is limited by inadequate annotation of primary miRNA (pri-miRNA) transcripts. Here, we used CAGE-seq and RNA-seq to provide genome-wide identification of the pri-miRNA core promoter repertoire and its dynamic usage during zebrafish embryogenesis. We assigned pri miRNA promoters to 152 precursor-miRNAs (pre-miRNAs), the majority of which were supported by promoter associated post-translational histone modifications (H3K4me3, H2A.Z) and RNA polymerase II (RNAPII) occupancy. We validated seven miR 9 pri-miRNAs by in situ hybridization and showed similar expression patterns as mature miR-9. In addition, processing of an alternative intronic promoter of miR 9-5 was validated by 5' RACE PCR. Developmental profiling revealed a subset of pri-miRNAs that are maternally inherited. Moreover, we show that promoter associated H3K4me3, H2A.Z and RNAPII marks are not only present at pri-miRNA promoters but are also specifically enriched at pre-miRNAs, suggesting chromatin level regulation of pre-miRNAs. Furthermore, we demonstrated that CAGE-seq also detects 3'-end processing of pre-miRNAs on Drosha cleavage site that correlates with miRNA-offset RNAs (moRNAs) production and provides a new tool for detecting Drosha processing events and predicting pre-miRNA processing by a genome-wide assay. PMID- 26673699 TI - Cancer-predisposition gene KLLN maintains pericentric H3K9 trimethylation protecting genomic stability. AB - Maintenance of proper chromatin states and genomic stability is vital for normal development and health across a range of organisms. Here, we report on the role of KLLN in maintenance of pericentric H3K9 trimethylation (H3K9me3) and genomic stability. Germline hypermethylation of KLLN, a gene uncovered well after the human genome project, has been linked to Cowden cancer-predisposition syndrome (CS) in PTEN wild-type cases. KLLN first identified as a p53-dependent tumor suppressor gene, was believed to bind randomly to DNA and cause S-phase arrest. Using chromatin immunoprecipitation-based sequencing (ChIP-seq), we demonstrated that KLLN binds to DNA regions enriched with H3K9me3. KLLN overexpression correlated with increased H3K9 methyltransferase activity and increased global H3K9me3, while knockdown of KLLN had an opposite effect. We also found KLLN to localize to pericentric regions, with loss of KLLN resulting in dysregulation of pericentric heterochromatin, with consequent chromosomal instability manifested by increased micronuclei formation and numerical chromosomal aberrations. Interestingly, we show that KLLN interacts with DBC1, with consequent abrogation of DBC1 inhibition of SUV39H1, a H3K9 methyltransferase, suggesting the mode of KLLN regulating H3K9me3. These results suggest a critical role for KLLN as a potential regulator of pericentric heterochromatin formation, genomic stability and gene expression. PMID- 26673702 TI - The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. PMID- 26673700 TI - Readers of poly(ADP-ribose): designed to be fit for purpose. AB - Post-translational modifications (PTMs) regulate many aspects of protein function and are indispensable for the spatio-temporal regulation of cellular processes. The proteome-wide identification of PTM targets has made significant progress in recent years, as has the characterization of their writers, readers, modifiers and erasers. One of the most elusive PTMs is poly(ADP-ribosyl)ation (PARylation), a nucleic acid-like PTM involved in chromatin dynamics, genome stability maintenance, transcription, cell metabolism and development. In this article, we provide an overview on our current understanding of the writers of this modification and their targets, as well as the enzymes that degrade and thereby modify and erase poly(ADP-ribose) (PAR). Since many cellular functions of PARylation are exerted through dynamic interactions of PAR-binding proteins with PAR, we discuss the readers of this modification and provide a synthesis of recent findings, which suggest that multiple structurally highly diverse reader modules, ranging from completely folded PAR-binding domains to intrinsically disordered sequence stretches, evolved as PAR effectors to carry out specific cellular functions. PMID- 26673701 TI - Directing an artificial zinc finger protein to new targets by fusion to a non-DNA binding domain. AB - Transcription factors are often regarded as having two separable components: a DNA-binding domain (DBD) and a functional domain (FD), with the DBD thought to determine target gene recognition. While this holds true for DNA bindingin vitro, it appears thatin vivoFDs can also influence genomic targeting. We fused the FD from the well-characterized transcription factor Kruppel-like Factor 3 (KLF3) to an artificial zinc finger (AZF) protein originally designed to target the Vascular Endothelial Growth Factor-A (VEGF-A) gene promoter. We compared genome wide occupancy of the KLF3FD-AZF fusion to that observed with AZF. AZF bound to theVEGF-Apromoter as predicted, but was also found to occupy approximately 25,000 other sites, a large number of which contained the expected AZF recognition sequence, GCTGGGGGC. Interestingly, addition of the KLF3 FD re-distributes the fusion protein to new sites, with total DNA occupancy detected at around 50,000 sites. A portion of these sites correspond to known KLF3-bound regions, while others contained sequences similar but not identical to the expected AZF recognition sequence. These results show that FDs can influence and may be useful in directing AZF DNA-binding proteins to specific targets and provide insights into how natural transcription factors operate. PMID- 26673703 TI - The structural diversity of artificial genetic polymers. AB - Synthetic genetics is a subdiscipline of synthetic biology that aims to develop artificial genetic polymers (also referred to as xeno-nucleic acids or XNAs) that can replicate in vitro and eventually in model cellular organisms. This field of science combines organic chemistry with polymerase engineering to create alternative forms of DNA that can store genetic information and evolve in response to external stimuli. Practitioners of synthetic genetics postulate that XNA could be used to safeguard synthetic biology organisms by storing genetic information in orthogonal chromosomes. XNA polymers are also under active investigation as a source of nuclease resistant affinity reagents (aptamers) and catalysts (xenozymes) with practical applications in disease diagnosis and treatment. In this review, we provide a structural perspective on known antiparallel duplex structures in which at least one strand of the Watson-Crick duplex is composed entirely of XNA. Currently, only a handful of XNA structures have been archived in the Protein Data Bank as compared to the more than 100 000 structures that are now available. Given the growing interest in xenobiology projects, we chose to compare the structural features of XNA polymers and discuss their potential to access new regions of nucleic acid fold space. PMID- 26673704 TI - Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus. AB - Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms.CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. We found the boundaries of the CFTRTAD are conserved among diverse cell types and are dependent on CTCF and cohesin complex. Removal of an upstream CTCF-binding insulator alters the interaction profile, but has little effect on CFTR expression. Within the TAD, intronic enhancers recruit cell-type selective transcription factors and deletion of a pivotal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structure. PMID- 26673705 TI - The European Bioinformatics Institute in 2016: Data growth and integration. AB - New technologies are revolutionising biological research and its applications by making it easier and cheaper to generate ever-greater volumes and types of data. In response, the services and infrastructure of the European Bioinformatics Institute (EMBL-EBI, www.ebi.ac.uk) are continually expanding: total disk capacity increases significantly every year to keep pace with demand (75 petabytes as of December 2015), and interoperability between resources remains a strategic priority. Since 2014 we have launched two new resources: the European Variation Archive for genetic variation data and EMPIAR for two-dimensional electron microscopy data, as well as a Resource Description Framework platform. We also launched the Embassy Cloud service, which allows users to run large analyses in a virtual environment next to EMBL-EBI's vast public data resources. PMID- 26673706 TI - A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei. AB - Antigenic variation in Trypanosoma brucei relies on periodic switching of variant surface glycoproteins (VSGs), which are transcribed monoallelically by RNA polymerase I from one of about 15 bloodstream expression sites (BES). Chromatin of the actively transcribed BES is depleted of nucleosomes, but it is unclear if this open conformation is a mere consequence of a high rate of transcription, or whether it is maintained by a transcription-independent mechanism. Using an inducible BES-silencing reporter strain, we observed that chromatin of the active BES remains open for at least 24 hours after blocking transcription. This conformation is independent of the cell-cycle stage, but dependent upon TDP1, a high mobility group box protein. For two days after BES silencing, we detected a transient and reversible derepression of several silent BESs within the population, suggesting that cells probe other BESs before commitment to one, which is complete by 48 hours. FACS sorting and subsequent subcloning confirmed that probing cells are switching intermediates capable of returning to the original BES, switch to the probed BES or to a different BES. We propose that regulation of BES chromatin structure is an epigenetic mechanism important for successful antigenic switching. PMID- 26673707 TI - Cap homeostasis is independent of poly(A) tail length. AB - Cap homeostasis is a cyclical process of decapping and recapping that maintains the cap on a subset of the cytoplasmic transcriptome. Interfering with cytoplasmic capping results in the redistribution of target transcripts from polysomes to non-translating mRNPs, where they accumulate in an uncapped but nonetheless stable form. It is generally thought that decapping is preceded by shortening of the poly(A) tail to a length that can no longer support translation. Therefore recapped target transcripts would either have to undergo cytoplasmic polyadenylation or retain a reasonably long poly(A) tail if they are to return to the translating pool. In cells that are inhibited for cytoplasmic capping there is no change in the overall distribution of poly(A) lengths or in the elution profile of oligo(dT)-bound targets. Poly(A) tail lengths were similar for target mRNAs on polysomes or in non-translating mRNPs, and the presence of polyadenylated uncapped mRNA in mRNPs was confirmed by separation into capped and uncapped pools prior to assay. Finally, in silico analysis of cytoplasmic capping targets revealed significant correlations with genes encoding transcripts with uridylated or multiply modified 3' ends, and genes possessing multiple 3' untranslated regions (UTRs) generated by alternative cleavage and polyadenylation. PMID- 26673708 TI - A novel RNA-binding mode of the YTH domain reveals the mechanism for recognition of determinant of selective removal by Mmi1. AB - The YTH domain-containing protein Mmi1, together with other factors, constitutes the machinery used to selectively remove meiosis-specific mRNA during the vegetative growth of fission yeast. Mmi1 directs meiotic mRNAs to the nuclear exosome for degradation by recognizing their DSR (determinant of selective removal) motif. Here, we present the crystal structure of the Mmi1 YTH domain in the apo state and in complex with a DSR motif, demonstrating that the Mmi1 YTH domain selectively recognizes the DSR motif. Intriguingly, Mmi1 also contains a potential m(6)A (N(6)-methyladenine)-binding pocket, but its binding of the DSR motif is dependent on a long groove opposite the m(6)A pocket. The DSR-binding mode is distinct from the m(6)A RNA-binding mode utilized by other YTH domains. Furthermore, the m(6)A pocket cannot bind m(6)A RNA. Our structural and biochemical experiments uncover the mechanism of the YTH domain in binding the DSR motif and help to elucidate the function of Mmi1. PMID- 26673709 TI - Different duplex/quadruplex junctions determine the properties of anti-thrombin aptamers with mixed folding. AB - Mixed duplex/quadruplex oligonucleotides have attracted great interest as therapeutic targets as well as effective biomedical aptamers. In the case of thrombin-binding aptamer (TBA), the addition of a duplex motif to the G quadruplex module improves the aptamer resistance to biodegradation and the affinity for thrombin. In particular, the mixed oligonucleotide RE31 is significantly more effective than TBA in anticoagulation experiments and shows a slower disappearance rate in human plasma and blood. In the crystal structure of the complex with thrombin, RE31 adopts an elongated structure in which the duplex and quadruplex regions are perfectly stacked on top of each other, firmly connected by a well-structured junction. The lock-and-key shape complementarity between the TT loops of the G-quadruplex and the protein exosite I gives rise to the basic interaction that stabilizes the complex. However, our data suggest that the duplex motif may have an active role in determining the greater anti-thrombin activity in biological fluids with respect to TBA. This work gives new information on mixed oligonucleotides and highlights the importance of structural data on duplex/quadruplex junctions, which appear to be varied, unpredictable, and fundamental in determining the aptamer functional properties. PMID- 26673710 TI - Conservative site-specific and single-copy transgenesis in human LINE-1 elements. AB - Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage lambda integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, term edattH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis through attH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional in LINE1-targeted hESCs and differentiated progenies. Furthermore, LINE-1 targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi transgenes. PMID- 26673711 TI - MethylAction: detecting differentially methylated regions that distinguish biological subtypes. AB - DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction. PMID- 26673713 TI - canSAR: an updated cancer research and drug discovery knowledgebase. AB - canSAR (http://cansar.icr.ac.uk) is a publicly available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery. canSAR integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and druggability data. canSAR is widely used to rapidly access information and help interpret experimental data in a translational and drug discovery context. Here we describe major enhancements to canSAR including new data, improved search and browsing capabilities, new disease and cancer cell line summaries and new and enhanced batch analysis tools. PMID- 26673712 TI - Cold-inducible RNA-binding protein CIRP/hnRNP A18 regulates telomerase activity in a temperature-dependent manner. AB - The telomerase is responsible for adding telomeric repeats to chromosomal ends and consists of the reverse transcriptase TERT and the RNA subunit TERC. The expression and activity of the telomerase are tightly regulated, and aberrant activation of the telomerase has been observed in >85% of human cancers. To better understand telomerase regulation, we performed immunoprecipitations coupled with mass spectrometry (IP-MS) and identified cold inducible RNA-binding protein (CIRP or hnRNP A18) as a telomerase-interacting factor. We have found that CIRP is necessary to maintain telomerase activities at both 32 degrees C and 37 degrees C. Furthermore, inhibition of CIRP by CRISPR-Cas9 or siRNA knockdown led to reduced telomerase activities and shortened telomere length, suggesting an important role of CIRP in telomere maintenance. We also provide evidence here that CIRP associates with the active telomerase complex through direct binding of TERC and regulates Cajal body localization of the telomerase. In addition, CIRP regulates the level of TERT mRNAs. At the lower temperature, TERT mRNA is upregulated in a CIRP-dependent manner to compensate for reduced telomerase activities. Taken together, these findings highlight the dual roles that CIRP plays in regulating TERT and TERC, and reveal a new class of telomerase modulators in response to hypothermia conditions. PMID- 26673714 TI - Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light. AB - Programmable transcription factors can enable precise control of gene expression triggered by a chemical inducer or light. To obtain versatile transgene system with combined benefits of a chemical inducer and light inducer, we created various chimeric promoters through the assembly of different copies of the tet operator and Gal4 operator module, which simultaneously responded to a tetracycline-responsive transcription factor and a light-switchable transactivator. The activities of these chimeric promoters can be regulated by tetracycline and blue light synergistically or antagonistically. Further studies of the antagonistic genetic circuit exhibited high spatiotemporal resolution and extremely low leaky expression, which therefore could be used to spatially and stringently control the expression of highly toxic protein Diphtheria toxin A for light regulated gene therapy. When transferring plasmids engineered for the gene switch-driven expression of a firefly luciferase (Fluc) into mice, the Fluc expression levels of the treated animals directly correlated with the tetracycline and light input program. We suggest that dual-input genetic circuits using TET and light that serve as triggers to achieve expression profiles may enable the design of robust therapeutic gene circuits for gene- and cell-based therapies. PMID- 26673715 TI - Structural requirements for protein-catalyzed annealing of U4 and U6 RNAs during di-snRNP assembly. AB - Base-pairing of U4 and U6 snRNAs during di-snRNP assembly requires large-scale remodeling of RNA structure that is chaperoned by the U6 snRNP protein Prp24. We investigated the mechanism of U4/U6 annealing in vitro using an assay that enables visualization of ribonucleoprotein complexes and faithfully recapitulates known in vivo determinants for the process. We find that annealing, but not U6 RNA binding, is highly dependent on the electropositive character of a 20 A-wide groove on the surface of Prp24. During annealing, we observe the formation of a stable ternary complex between U4 and U6 RNAs and Prp24, indicating that displacement of Prp24 in vivo requires additional factors. Mutations that stabilize the U6 'telestem' helix increase annealing rates by up to 15-fold, suggesting that telestem formation is rate-limiting for U4/U6 pairing. The Lsm2-8 complex, which binds adjacent to the telestem at the 3' end of U6, provides a comparable rate enhancement. Collectively, these data identify domains of the U6 snRNP that are critical for one of the first steps in assembly of the megaDalton U4/U6.U5 tri-snRNP complex, and lead to a dynamic model for U4/U6 pairing that involves a striking degree of evolved cooperativity between protein and RNA. PMID- 26673716 TI - The Pfam protein families database: towards a more sustainable future. AB - In the last two years the Pfam database (http://pfam.xfam.org) has undergone a substantial reorganisation to reduce the effort involved in making a release, thereby permitting more frequent releases. Arguably the most significant of these changes is that Pfam is now primarily based on the UniProtKB reference proteomes, with the counts of matched sequences and species reported on the website restricted to this smaller set. Building families on reference proteomes sequences brings greater stability, which decreases the amount of manual curation required to maintain them. It also reduces the number of sequences displayed on the website, whilst still providing access to many important model organisms. Matches to the full UniProtKB database are, however, still available and Pfam annotations for individual UniProtKB sequences can still be retrieved. Some Pfam entries (1.6%) which have no matches to reference proteomes remain; we are working with UniProt to see if sequences from them can be incorporated into reference proteomes. Pfam-B, the automatically-generated supplement to Pfam, has been removed. The current release (Pfam 29.0) includes 16 295 entries and 559 clans. The facility to view the relationship between families within a clan has been improved by the introduction of a new tool. PMID- 26673718 TI - A comprehensive comparison of general RNA-RNA interaction prediction methods. AB - RNA-RNA interactions are fast emerging as a major functional component in many newly discovered non-coding RNAs. Basepairing is believed to be a major contributor to the stability of these intermolecular interactions, much like intramolecular basepairs formed in RNA secondary structure. As such, using algorithms similar to those for predicting RNA secondary structure, computational methods have been recently developed for the prediction of RNA-RNA interactions. We provide the first comprehensive comparison comprising 14 methods that predict general intermolecular basepairs. To evaluate these, we compile an extensive data set of 54 experimentally confirmed fungal snoRNA-rRNA interactions and 102 bacterial sRNA-mRNA interactions. We test the performance accuracy of all methods, evaluating the effects of tool settings, sequence length, and multiple sequence alignment usage and quality. Our results show that-unlike for RNA secondary structure prediction--the overall best performing tools are non comparative energy-based tools utilizing accessibility information that predict short interactions on this data set. Furthermore, we find that maintaining high accuracy across biologically different data sets and increasing input lengths remains a huge challenge, causing implications for de novo transcriptome-wide searches. Finally, we make our interaction data set publicly available for future development and benchmarking efforts. PMID- 26673717 TI - L1 retrotransposition requires rapid ORF1p oligomerization, a novel coiled coil dependent property conserved despite extensive remodeling. AB - Detailed mechanistic understanding of L1 retrotransposition is sparse, particularly with respect to ORF1p, a coiled coil-mediated homotrimeric nucleic acid chaperone that can form tightly packed oligomers on nucleic acids. Although the coiled coil motif is highly conserved, it is uniquely susceptible to evolutionary change. Here we studied three ORF1 proteins: a modern human one (111p), its resuscitated primate ancestor (555p) and a mosaic modern protein (151p) wherein 9 of the 30 coiled coil substitutions retain their ancestral state. While 111p and 555p equally supported retrotransposition, 151p was inactive. Nonetheless, they were fully active in bulk assays of nucleic acid interactions including chaperone activity. However, single molecule assays showed that 151p trimers form stably bound oligomers on ssDNA at <1/10th the rate of the active proteins, revealing that oligomerization rate is a novel critical parameter of ORF1p activity in retrotransposition conserved for at least the last 25 Myr of primate evolution. PMID- 26673719 TI - Functional dissection of a plant Argonaute. AB - RNA guided ribonuclease complexes play central role in RNA interference. Members of the evolutionarily conserved Argonaute protein family form the catalytic cores of these complexes. Unlike a number of other plant Argonautes, the role of AGO2 has been obscure until recently. Newer data, however, have indicated its involvement in various biotic and abiotic stress responses. Despite its suggested importance, there is no detailed characterization of this protein to date. Here we report cloning and molecular characterization of the AGO2 protein of the virological model plant Nicotiana benthamiana. We show that AGO2 can directly repress translation via various miRNA target site constellations (ORF, 3' UTR). Interestingly, although AGO2 seems to be able to silence gene expression in a slicing independent fashion, its catalytic activity is still a prerequisite for efficient translational repression. Additionally, mismatches between the 3' end of the miRNA guide strand and the 5' end of the target site enhance gene silencing by AGO2. Several functionally important amino acid residues of AGO2 have been identified that affect its small RNA loading, cleavage activity, translational repression potential and antiviral activity. The data presented here help us to understand how AGO2 aids plants to deal with stress. PMID- 26673720 TI - Single molecule detection of PARP1 and PARP2 interaction with DNA strand breaks and their poly(ADP-ribosyl)ation using high-resolution AFM imaging. AB - PARP1 and PARP2 are implicated in the synthesis of poly(ADP-ribose) (PAR) after detection of DNA damage. The specificity of PARP1 and PARP2 interaction with long DNA fragments containing single- and/or double-strand breaks (SSBs and DSBs) have been studied using atomic force microscopy (AFM) imaging in combination with biochemical approaches. Our data show that PARP1 localizes mainly on DNA breaks and exhibits a slight preference for nicks over DSBs, although the protein has a moderately high affinity for undamaged DNA. In contrast to PARP1, PARP2 is mainly detected at a single DNA nick site, exhibiting a low level of binding to undamaged DNA and DSBs. The enhancement of binding affinity of PARP2 for DNA containing a single nick was also observed using fluorescence titration. AFM studies reveal that activation of both PARPs leads to the synthesis of highly branched PAR whose size depends strongly on the presence of SSBs and DSBs for PARP1 and of SSBs for PARP2. The initial affinity between the PARP1, PARP2 and the DNA damaged site appears to influence both the size of the PAR synthesized and the time of residence of PARylated PARP1 and PARP2 on DNA damages. PMID- 26673722 TI - The Arabidopsis homologs of trithorax (ATX1) and enhancer of zeste (CLF) establish 'bivalent chromatin marks' at the silent AGAMOUS locus. PMID- 26673721 TI - DNA recognition for virus assembly through multiple sequence-independent interactions with a helix-turn-helix motif. AB - The helix-turn-helix (HTH) motif features frequently in protein DNA-binding assemblies. Viral pac site-targeting small terminase proteins possess an unusual architecture in which the HTH motifs are displayed in a ring, distinct from the classical HTH dimer. Here we investigate how such a circular array of HTH motifs enables specific recognition of the viral genome for initiation of DNA packaging during virus assembly. We found, by surface plasmon resonance and analytical ultracentrifugation, that individual HTH motifs of the Bacillus phage SF6 small terminase bind the packaging regions of SF6 and related SPP1 genome weakly, with little local sequence specificity. Nuclear magnetic resonance chemical shift perturbation studies with an arbitrary single-site substrate suggest that the HTH motif contacts DNA similarly to how certain HTH proteins contact DNA non specifically. Our observations support a model where specificity is generated through conformational selection of an intrinsically bent DNA segment by a ring of HTHs which bind weakly but cooperatively. Such a system would enable viral gene regulation and control of the viral life cycle, with a minimal genome, conferring a major evolutionary advantage for SPP1-like viruses. PMID- 26673723 TI - G-quadruplexes with (4n - 1) guanines in the G-tetrad core: formation of a G triad.water complex and implication for small-molecule binding. AB - G-quadruplexes are non-canonical structures of nucleic acids, in which guanine bases form planar G-tetrads (G.G.G.G) that stack on each other in the core of the structure. G-quadruplexes generally contain multiple times of four (4n) guanines in the core. Here, we study the structure of G-quadruplexes with only (4n - 1) guanines in the core. The solution structure of a DNA sequence containing 11 guanines showed the formation of a parallel G-quadruplex involving two G-tetrads and one G-triad with a vacant site. Molecular dynamics simulation established the formation of a stable G-triad.water complex, where water molecules mimic the position of the missing guanine in the vacant site. The concept of forming G quadruplexes with missing guanines in the core broadens the current definition of G-quadruplex-forming sequences. The potential ability of such structures to bind different metabolites, including guanine, guanosine and GTP, in the vacant site, could have biological implications in regulatory functions. Formation of this unique binding pocket in the G-triad could be used as a specific target in drug design. PMID- 26673724 TI - A human transcription factor in search mode. AB - Transcription factors (TF) can change shape to bind and recognize DNA, shifting the energy landscape from a weak binding, rapid search mode to a higher affinity recognition mode. However, the mechanism(s) driving this conformational change remains unresolved and in most cases high-resolution structures of the non specific complexes are unavailable. Here, we investigate the conformational switch of the human mitochondrial transcription termination factor MTERF1, which has a modular, superhelical topology complementary to DNA. Our goal was to characterize the details of the non-specific search mode to complement the crystal structure of the specific binding complex, providing a basis for understanding the recognition mechanism. In the specific complex, MTERF1 binds a significantly distorted and unwound DNA structure, exhibiting a protein conformation incompatible with binding to B-form DNA. In contrast, our simulations of apo MTERF1 revealed significant flexibility, sampling structures with superhelical pitch and radius complementary to the major groove of B-DNA. Docking these structures to B-DNA followed by unrestrained MD simulations led to a stable complex in which MTERF1 was observed to undergo spontaneous diffusion on the DNA. Overall, the data support an MTERF1-DNA binding and recognition mechanism driven by intrinsic dynamics of the MTERF1 superhelical topology. PMID- 26673725 TI - A mass spectrometry-based method for direct determination of pseudouridine in RNA. AB - Pseudouridine (5-ribosyluracil, Psi) is the only 'mass-silent' nucleoside produced by post-transcriptional RNA modification. We describe here a novel mass spectrometry (MS)-based method for direct determination of Psi in RNA. The method assigns a Psi-containing nucleolytic RNA fragment by an accurate measurement of a signature doubly dehydrated nucleoside anion ([C9H7N2O4](1-),m/z207.04) produced by collision-induced dissociation MS, and it determines the Psi-containing nucleotide sequence by pseudo-MS(3), i.e. in-source fragmentation followed by MS(2) By applying this method, we identified all of the known Psis in the canonical human spliceosomal snRNAs and, unexpectedly, found two previously unknown Psis in the U5 and U6 snRNAs. Because the method allows direct determination of Psi in a subpicomole quantity of RNA, it will serve as a useful tool for the structure/function studies of a wide variety of non-coding RNAs. PMID- 26673728 TI - Modelling the biological invasion of Carcinus maenas (the European green crab). AB - This paper proposes a system of integro-difference equations to model the spread of Carcinus maenas, commonly called the European green crab, that causes severe damage to coastal ecosystems. A model with juvenile and adult classes is first studied. Here, standard theory of monotone operators for integro-difference equations can be applied and yields explicit formulas for the asymptotic spreading speeds of the juvenile and adult crabs. A second model including an infected class is considered by introducing a castrating parasite Sacculina carcini as a biological control agent. The dynamics are complicated and simulations reveal the occurrence of periodic solutions and stacked fronts. In this case, only conjectures can be made for the asymptotic spreading speeds because of the lack of mathematical theory for non-monotone operators. This paper also emphasizes the need for mathematical studies of non-monotone operators in heterogeneous environments and the existence of stacked front solutions in biological invasion models. PMID- 26673726 TI - Structural and functional insights into tRNA binding and adenosine N1-methylation by an archaeal Trm10 homologue. AB - Purine nucleosides on position 9 of eukaryal and archaeal tRNAs are frequently modified in vivo by the post-transcriptional addition of a methyl group on their N1 atom. The methyltransferase Trm10 is responsible for this modification in both these domains of life. While certain Trm10 orthologues specifically methylate either guanosine or adenosine at position 9 of tRNA, others have a dual specificity. Until now structural information about this enzyme family was only available for the catalytic SPOUT domain of Trm10 proteins that show specificity toward guanosine. Here, we present the first crystal structure of a full length Trm10 orthologue specific for adenosine, revealing next to the catalytic SPOUT domain also N- and C-terminal domains. This structure hence provides crucial insights in the tRNA binding mechanism of this unique monomeric family of SPOUT methyltransferases. Moreover, structural comparison of this adenosine-specific Trm10 orthologue with guanosine-specific Trm10 orthologues suggests that the N1 methylation of adenosine relies on additional catalytic residues. PMID- 26673727 TI - The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats. AB - Eukaryotic chromatin is a complex yet dynamic structure, which is regulated in part by the assembly and disassembly of nucleosomes. Key to this process is a group of proteins termed histone chaperones that guide the thermodynamic assembly of nucleosomes by interacting with soluble histones. Here we investigate the interaction between the histone chaperone sNASP and its histone H3 substrate. We find that sNASP binds with nanomolar affinity to a conserved heptapeptide motif in the globular domain of H3, close to the C-terminus. Through functional analysis of sNASP homologues we identified point mutations in surface residues within the TPR domain of sNASP that disrupt H3 peptide interaction, but do not completely disrupt binding to full length H3 in cells, suggesting that sNASP interacts with H3 through additional contacts. Furthermore, chemical shift perturbations from(1)H-(15)N HSQC experiments show that H3 peptide binding maps to the helical groove formed by the stacked TPR motifs of sNASP. Our findings reveal a new mode of interaction between a TPR repeat domain and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants, including CenpA and have implications for the mechanism of histone chaperoning within the cell. PMID- 26673729 TI - Size Determination of a Liposomal Drug by Small-Angle X-ray Scattering Using Continuous Contrast Variation. AB - The continuously growing complexity of nanodrugs urges for complementary characterization techniques which can elude the current limitations. In this paper, the applicability of continuous contrast variation in small-angle X-ray scattering (SAXS) for the accurate size determination of a complex nanocarrier is demonstrated on the example of PEGylated liposomal doxorubicin (Caelyx). The mean size and average electron density of Caelyx was determined by SAXS using a gradient of aqueous iodixanol (Optiprep), an iso-osmolar suspending medium. The study is focused on the isoscattering point position and the analysis of the Guinier region of the scattering curves recorded at different solvent densities. An average diameter of (69 +/- 5) nm and electron density of (346.2 +/- 1.2) nm( 3) were determined for the liposomal formulation of doxorubicin. The response of the liposomal nanocarrier to increasing solvent osmolality and the structure of the liposome-encapsulated doxorubicin after the osmotic shrinkage of the liposome are evaluated with sucrose contrast variation in SAXS and wide-angle X-ray scattering (WAXS). In the case of using sucrose as contrast agent, a clear osmolality threshold at 670 mOsm kg(-1) was observed, above which the liposomal drug carriers start to shrink, though preserving the intraliposomal doxorubicin structure. The average size obtained by this technique is smaller than the value measured by dynamic light scattering (DLS), though this difference is expected due to the hydrodynamic size of the PEG moieties attached to the liposomal surface, which are not probed with solvent contrast variation in SAXS. The advantages and drawbacks of the proposed technique are discussed in comparison to DLS, the most frequently used sizing method in nanomedicine. PMID- 26673731 TI - Corrigendum: Transitivity in Arabidopsis can be primed, requires the redundant action of the antiviral Dicer-like 4 and Dicer-like 2, and is compromised by viral-encoded suppressor proteins. PMID- 26673730 TI - Acute Pain and Depressive Symptoms: Independent Predictors of Insomnia Symptoms among Adults with Sickle Cell Disease. AB - No studies to date have systematically investigated insomnia symptoms among adults with sickle cell disease (SCD). The purpose of this study was to (1) describe the prevalence of insomnia symptoms and (2) identify biopsychosocial predictors in community-dwelling adults with SCD. Cross-sectional analysis of baseline data from 263 African American adults with SCD (aged 18 years or older). Measures included the Insomnia Severity Index (ISI), Center for Epidemiologic Studies in Depression scale, Urban Life Stress Scale, Brief Pain Inventory, and a chronic pain item. SCD genotype was extracted from the medical record. A slight majority (55%) of the sample reported clinically significant insomnia symptomatology (ISI >= 10), which suggests that insomnia symptoms are prevalent among community-dwelling African American adults with SCD. While insomnia symptoms were associated with a number of biopsychosocial characteristics, depressive symptoms and acute pain were the only independent predictors. Given the high number of participants reporting clinically significant insomnia symptoms, nurses should screen for insomnia symptoms and explore interventions to promote better sleep among adults with SCD, with an emphasis on recommending treatment for pain and depression. In addition, current pain and depression interventions in this population could add insomnia measures and assess the effect of the intervention on insomnia symptomatology as a secondary outcome. PMID- 26673732 TI - Corrigendum: Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells. PMID- 26673733 TI - Fragmentation reactions using electrospray ionization mass spectrometry: an important tool for the structural elucidation and characterization of synthetic and natural products. AB - Over the last decade, the number of studies reporting the use of electrospray ionization mass spectrometry (ESI-MS) in combination with collision cells (or other activation methods) to promote fragmentation of synthetic and natural products for structural elucidation purposes has considerably increased. However, the lack of a systematic compilation of the gas-phase fragmentation reactions subjected to ESI-MS/MS conditions still represents a challenge and has led to many misunderstood results in the literature. This review article exploits the most common fragmentation reactions for ions generated by ESI in positive and negative modes using collision cells in an effort to stimulate the use of this technique by non-specialists, undergraduate students and researchers in related areas. PMID- 26673734 TI - From one Nobel Prize (P. Ehrlich) to another (Tu Youyou): 100 years of chemotherapy of infectious diseases. PMID- 26673735 TI - Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. AB - Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease. PMID- 26673736 TI - Hybrid Amyloid Membranes for Continuous Flow Catalysis. AB - Amyloid fibrils are promising nanomaterials for technological applications such as biosensors, tissue engineering, drug delivery, and optoelectronics. Here we show that amyloid-metal nanoparticle hybrids can be used both as efficient active materials for wet catalysis and as membranes for continuous flow catalysis applications. Initially, amyloid fibrils generated in vitro from the nontoxic beta-lactoglobulin protein act as templates for the synthesis of gold and palladium metal nanoparticles from salt precursors. The resulting hybrids possess catalytic features as demonstrated by evaluating their activity in a model catalytic reaction in water, e.g., the reduction of 4-nitrophenol into 4 aminophenol, with the rate constant of the reduction increasing with the concentration of amyloid-nanoparticle hybrids. Importantly, the same nanoparticles adsorbed onto fibrils surface show improved catalytic efficiency compared to the same unattached particles, pointing at the important role played by the amyloid fibril templates. Then, filter membranes are prepared from the metal nanoparticle-decorated amyloid fibrils by vacuum filtration. The resulting membranes serve as efficient flow catalysis active materials, with a complete catalytic conversion achieved within a single flow passage of a feeding solution through the membrane. PMID- 26673737 TI - MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis. AB - BACKGROUND: Even though increasing evidences on miRNA involvement in human pathological responses, the distinct roles and related mechanisms of miRNAs in the pathology of osteoarthritis (OA) are not yet fully understood. METHOD: RNA levels or protein levels of Apoptotic genes, HDACs, MMP-13, and miRNAs in human chondrocytes isolated from normal biopsy sample and OA cartilages were analyzed by real-time PCR or western blotting. Exogenous modulation of miR-222 level was performed using delivery of its specific precursor or specific inhibitor and target validation assay was applied to identify its potent target. In vivo study using DMM mice model was performed and assessed the degree of cartilage degradation. RESULTS: According to miRNA profiling, miR-222 was significantly down-regulated in OA chondrocytes. Over-expression of miR-222 significantly suppressed apoptotic death by down-regulating HDAC-4 and MMP-13 level. Moreover, 3'-UTR reporter assays showed that HDAC-4 is a direct target of miR-222. The treatment of chondrocytes with the HDAC inhibitor, trichostatin A (TSA), suppressed MMP-13 protein level and apoptosis, whereas the over-expression of HDAC-4 displayed opposite effects. The introduction of miR-222 into the cartilage of medial meniscus destabilized mice significantly reduced cartilage destruction and MMP-13 level. CONCLUSION: Taken together, our data suggest that miR-222 may be involved in cartilage destruction by targeting HDAC-4 and regulating MMP-13 level. PMID- 26673738 TI - Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-Positive T cells expressing IL-1 receptor type 2 and regulatory T Cells. AB - BACKGROUND: Accumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear. RESULTS: We have shown that age-related developments of T-cell dysfunction, hearing loss, and degeneration of cochlear spiral ganglion (SG) neurons observed in 6-month-old mice were recovered in 12 months old mice which previously given fetal thymus transplants twice. We have also demonstrated that CD4(+) T cells expressing interleukin 1 receptor type 2 (IL-1R2) and naturally occurring regulatory T cells (nTregs), which expanded in aged 12-month-old mice, were reduced in the thymus-grafted mice of the same age. CONCLUSION: It is conceivable that the rejuvenation of systemic immune function by fetal thymus grafts contributes not only to the activation of cellular immunity but also to the decrease of IL-1R2(+) CD4(+) T cells or nTregs, which cells accelerate both age related hearing loss (AHL) and neurodegeneration of the cochlear neurons. Further studies on the interactions among IL-1R2 expression on CD4(+) T cells, Tregs, and neuronal cells and also on the relationships between fetal thymus grafting and the rejuvenation of systemic immunity should be designed in order to advance towards therapeutic effects on neurosenescence, including AHL. PMID- 26673739 TI - Ethylene polymerization by salicylaldimine nickel(II) complexes containing a dibenzhydryl moiety. AB - The synthesis, characterization and ethylene polymerization properties of a series of salicylaldimine Ni(ii) complexes with a dibenzhydryl moiety are described. These Ni complexes are designed to bear systematically varied electron donating and withdrawing substituents. These complexes are among the most active salicylaldimine Ni(ii) catalysts in ethylene polymerization. Moreover, these complexes demonstrate good thermal stability, maintaining high activity at 80 degrees C. The polyethylene generated possesses a high molecular weight, moderate branching density and high melting temperature. Surprisingly, the electronic perturbations only exert moderate influence on the ethylene polymerization process despite the covalently close proximity of the electron donating or withdrawing substituents to the metal center. Comparing with the traditional iso propyl substituted nickel analogue, these new complexes show up to an order of magnitude higher activity, generating polyethylene with much higher molecular weight, similar or slightly lower branching density and much higher melting temperature. PMID- 26673740 TI - In vitro bidirectional permeability studies identify pharmacokinetic limitations of NKCC1 inhibitor bumetanide. AB - Recently, it has been suggested that bumetanide, an inhibitor of the Na-K-2Cl co transporter (NKCC1), may be useful in the treatment of central nervous system (CNS) disorders. However, from a physicochemical perspective, bumetanide may not cross the blood-brain barrier to the extent that is necessary for it to be an effective brain NKCC1 inhibitor in vivo. High plasma-protein binding, potentially high brain-tissue binding and putative efflux transporters including organic anion transporter 3 (OAT3) contribute to the poor pharmacokinetic profile of bumetanide. Bidirectional permeability assays are an in vitro method to determine the impact of plasma-protein/brain tissue binding, as well as efflux transport, on the permeability of a compound. We established and validated a cell line stably overexpressing human OAT3 using lentiviral cloning techniques for use in in vitro bidirectional permeability assays. Using efflux transport studies, we show that bumetanide is a transported substrate of human OAT3, exhibiting a transport ratio of >=1.5, which is attenuated by OAT3 inhibitors. Bidirectional permeability assays were carried out in the presence and absence of either albumin or brain homogenate to elucidate the effect of plasma-protein/brain tissue binding. These tests confirmed the pharmacokinetic limitations for brain delivery of bumetanide. In this experiment, bumetanide is 53% bound to albumin, 77% bound to brain tissue and accumulates in brain cells. Moreover, we conclusively established that bumetanide is a transported substrate of OAT3. Taken together, these bidirectional permeability studies highlight the potential of efflux transporter inhibition as an augmentation strategy for enhanced delivery of bumetanide to the CNS. PMID- 26673741 TI - Deranged iron status in psoriasis: the impact of low body mass. AB - BACKGROUND: Iron deficiency (ID) frequently complicates inflammatory-mediated chronic disorders, irrespective of anaemia. Psoriasis is a chronic, immune mediated skin disease with systemic pro-inflammatory activation; thus, these patients may be prone to develop ID. ID adversely affects immune cells function, which can further contribute to disease progression. This study investigates iron status in psoriasis. METHODS: Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 39 patients with psoriasis (17 men, age: 47 +/- 10 years) and 44 healthy subjects (30 men, age: 53 +/- 6 years). RESULTS: Compared with healthy controls, patients with psoriasis demonstrated similar haematologic status but deranged iron status as evidenced by decreased Tsat and elevated sTfR (negative tissue iron balance) and low levels of hepcidin (depleted iron stores) (all P < 0.05 vs. controls). In patients, the levels of interleukin-6 (level of pro-inflammatory activation) significantly correlated with hepcidin (R = 0.54), but not with ferritin, Tsat, and sTfR. Biomarkers reflecting ID were not associated with the severity of the disease (assessed with the Psoriasis Area and Severity Index) but significantly correlated low body mass index (BMI). Patients with BMI < 24 kg/m(2) compared with those with BMI >= 24 kg/m(2) demonstrated lower levels of ferritin (40 +/- 30 vs. 186 +/- 128 ng/mL, P < 0.001) and hepcidin (4.9 +/- 2.3 vs. 10.7 +/- 6.7 ng/mL, P = 0.03). CONCLUSION: Psoriasis is associated with deranged iron status characterized by depleted iron stores with concomitant unmet cellular iron requirements. The magnitude of these abnormalities is particularly strong in patients with low body mass index. Whether iron deficiency may become a therapeutic target in psoriasis needs to be investigated. PMID- 26673742 TI - Preparation of a novel nanocomposite NaLuF4:Gd,Yb,Tm@SiO2@Ag@TiO2 with high photocatalytic activity driven by simulated solar light. AB - A novel nanocomposite photocatalyst NaLuF4:Gd,Yb,Tm@SiO2@Ag@TiO2 was developed for the first time. This composite material has a sandwich structure, including a NaLuF4:Gd,Yb,Tm upconversion nanocrystals (UCNCs) core, a media shell of amorphous SiO2 decorated with Ag nanoparticles, and an outer shell of anatase TiO2. The designed new structure takes advantage of the synergetic effect of UCNCs, Ag nanoparticles and TiO2. The UCNCs absorb near-infrared (NIR) light and transfer energy to TiO2, which extends the light responsive range of TiO2 to the NIR region. Ag nanoparticles not only enhance upconversion luminescence of the UCNCs but also enhance light harvesting and improve charge separation of TiO2. The results of photocatalytic applications show that the as-prepared catalyst has high photocatalytic activity. This study provides new insights into the fabrication of TiO2-based nanocomposite photocatalysts with high catalytic efficiency through effective integration of upconversion material, noble metal and TiO2 into a hetero-composite nanostructure. PMID- 26673743 TI - Measurement of the Nucleus Area and Nucleus/Cytoplasm and Mitochondria/Nucleus Ratios in Human Colon Tissues by Dual-Colour Two-Photon Microscopy Imaging. AB - We developed two-photon (TP) probes for DNA (ABI-Nu), cytoplasm (Pyr-CT), and mitochondria (BF-MT). We found that ABI-Nu binds to AT in the minor groove, while ABI-Nu and BF-MT are effective for tracking in the cytoplasm and mitochondria, respectively. These probes showed very large effective two-photon action cross section values of 2230, 1555, and 790 Goppert-Mayer units (1 GM = 10(-50) cm(4) s photon(-1) molecule(-1)) at 740 nm with emission maxima at 473, 561, and 560 nm, respectively, in each organelle. Using these probes, we quantitatively estimated the mean nuclear area and the ratios of nuclei to cytoplasm and mitochondria to nuclei in human colon tissues by dual-colour two-photon microscopy imaging within 2 h after biopsy. The mean nuclear area and the nuclei to cytoplasm and mitochondria to cytoplasm ratios increased in the following order: normal colon mucosa 3 years following the resumption of dermal substitute use in May 2012. PMID- 26673776 TI - A case report of aphallia with urorectal septum malformation sequence in a newborn: a very rarely seen condition. AB - Aphallia (absence of penis) is an extremely rare abnormality which has rarely been described in medical literature and can be part of the urorectal septum malformation sequence (URSMS). URSMS has hardly been reported in medical literature and includes the absence of perineal and anal openings in association with ambiguous genitalia and urogenital, colonic, and lumbosacral anomalies. This case report tells the importance of detailed examination of infants that are diagnosed with aphallia. We report a case of a newborn who was diagnosed as aphallia with the URSMS syndrome after birth. The neonate had an endocardial cushion defect (atrial septal defect and ventricular septal defect) and bilateral agenesis of the kidney. The neonate succumbed to death secondary to hypoplastic lung leading to respiratory failure. PMID- 26673777 TI - Scaling in Free-Swimming Fish and Implications for Measuring Size-at-Time in the Wild. AB - This study was motivated by the need to measure size-at-age, and thus growth rate, in fish in the wild. We postulated that this could be achieved using accelerometer tags based first on early isometric scaling models that hypothesize that similar animals should move at the same speed with a stroke frequency that scales with length-1, and second on observations that the speed of primarily air breathing free-swimming animals, presumably swimming 'efficiently', is independent of size, confirming that stroke frequency scales as length-1. However, such scaling relations between size and swimming parameters for fish remain mostly theoretical. Based on free-swimming saithe and sturgeon tagged with accelerometers, we introduce a species-specific scaling relationship between dominant tail beat frequency (TBF) and fork length. Dominant TBF was proportional to length-1 (r2 = 0.73, n = 40), and estimated swimming speed within species was independent of length. Similar scaling relations accrued in relation to body mass 0.29. We demonstrate that the dominant TBF can be used to estimate size-at-time and that accelerometer tags with onboard processing may be able to provide size at-time estimates among free-swimming fish and thus the estimation of growth rate (change in size-at-time) in the wild. PMID- 26673778 TI - Large-scale targeted sequencing comparison highlights extreme genetic heterogeneity in nephronophthisis-related ciliopathies. AB - BACKGROUND: The term nephronophthisis-related ciliopathies (NPHP-RC) describes a group of rare autosomal-recessive cystic kidney diseases, characterised by broad genetic and clinical heterogeneity. NPHP-RC is frequently associated with extrarenal manifestations and accounts for the majority of genetically caused chronic kidney disease (CKD) during childhood and adolescence. Generation of a molecular diagnosis has been impaired by this broad genetic heterogeneity. However, recently developed high-throughput exon sequencing techniques represent powerful and efficient tools to screen large cohorts for dozens of causative genes. METHODS: Therefore, we performed massively multiplexed targeted sequencing using the modified molecular inversion probe strategy (MIPs) in an international cohort of 384 patients diagnosed with NPHP-RC. RESULTS: As a result, we established the molecular diagnoses in 81/384 unrelated individuals (21.1%). We detected 127 likely disease-causing mutations in 18 of 34 evaluated NPHP-RC genes, 22 of which were novel. We further compared a subgroup of current findings to the results of a previous study in which we used an array-based microfluidic PCR technology in the same cohort. While 78 likely disease-causing mutations were previously detected by the array-based microfluidic PCR, the MIPs approach identified 94 likely pathogenic mutations. Compared with the previous approach, MIPs redetected 66 out of 78 variants and 28 previously unidentified variants, for a total of 94 variants. CONCLUSIONS: In summary, we demonstrate that the modified MIPs technology is a useful approach to screen large cohorts for a multitude of established NPHP genes in order to identify the underlying molecular cause. Combined application of two independent library preparation and sequencing techniques, however, may still be indicated for Mendelian diseases with extensive genetic heterogeneity in order to further increase diagnostic sensitivity. PMID- 26673779 TI - CRISPR-Cas9 for medical genetic screens: applications and future perspectives. AB - CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions. PMID- 26673781 TI - Time trends and sex differences in associations between socioeconomic status indicators and overweight-obesity in Mexico (2006-2012). AB - BACKGROUND: Although the associations between specific socioeconomic status (SES) indicators and overweight or obesity (OWOB) have been studied in different countries, fewer evidence exists for these associations when multiple SES indicators are considered simultaneously. Furthermore, there are few studies investigating time trends in OWOB and their relation with SES in upper-middle income countries, especially for men. The present study contributes to a better understanding of the nature and evolution of the associations between SES indicators and OWOB in the Mexican adult population. METHODS: We pooled data from the 2006 and 2012 National Health and Nutrition Surveys in Mexico and obtained covariate-adjusted prevalence from a design-based logistic multiple regression model. Covariates included a wealth index, education, occupational status, marital status, and all interactions for each covariate with sex (male/female) and survey year. RESULTS: For men, the association between wealth and OWOB remained positive in general but curvature was more evident in 2012. The wealth OWOB association in women showed an inverted-U pattern at both years with a positive slope that turned into a negative one as wealth increased. Among women, OWOB prevalence at the college/university education level was approximately 12.0 +/- 2.4 (percentage points +/- standard error) lower compared with the elementary education level. We did not find differences between educational categories for men in 2006, but in 2012 OWOB tended to be higher among the more educated. The prevalence of obesity in women increased at wealth levels from the middle and upper-middle section of the wealth distributions. Overall OWOB prevalence was near 70 % in 2012 for both sexes. CONCLUSIONS: Among Mexican women, the associations between SES indicators and excess body weight were consistent to those found in developed countries. Among Mexican men, higher education was not associated with a lower prevalence of OWOB but the positive association between wealth and OWOB weakened as wealth increased. The overall prevalence of OWOB was very high for both sexes; its reduction should remain a public health priority given the consequences of nutrition-related chronic diseases, disability and health care costs. PMID- 26673780 TI - Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites. AB - Neutrophil extracellular traps (NETs) extruded from neutrophils upon activation are composed of chromatin associated with cytosolic and granular proteins, which ensnare and kill microorganisms. This microbicidal mechanism named classical netosis has been shown to dependent on reactive oxygen species (ROS) generation by NADPH oxidase and also chromatin decondensation dependent upon the enzymes (PAD4), neutrophil elastase (NE) and myeloperoxidase (MPO). NET release also occurs through an early/rapid ROS-independent mechanism, named early/rapid vital netosis. Here we analyze the role of ROS, NE, MPO and PAD4 in the netosis stimulated by Leishmania amazonensis promastigotes in human neutrophils. We demonstrate that promastigotes induce a classical netosis, dependent on the cellular redox imbalance, as well as by a chloroamidine sensitive and elastase activity mechanism. Additionally, Leishmania also induces the early/rapid NET release occurring only 10 minutes after neutrophil-parasite interaction. We demonstrate here, that this early/rapid mechanism is dependent on elastase activity, but independent of ROS generation and chloroamidine. A better understanding of both mechanisms of NET release, and the NETs effects on the host immune system modulation, could support the development of new potential therapeutic strategies for leishmaniasis. PMID- 26673782 TI - Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells. AB - The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (alphaSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+ channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel activity comparable to bladder SMCs which may be important for urological regenerative medicine applications. PMID- 26673783 TI - Nitrite reductase is critical for Pseudomonas aeruginosa survival during co infection with the oral commensal Streptococcus parasanguinis. AB - Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in cystic fibrosis (CF) patients. However, recent evidence suggests that the polymicrobial community of the CF lung may also harbour oral streptococci, and colonization by these micro-organisms may have a negative impact on P. aeruginosa within the CF lung. Our previous studies demonstrated that nitrite abundance plays an important role in P. aeruginosa survival during co-infection with oral streptococci. Nitrite reductase is a key enzyme involved in nitrite metabolism. Therefore, the objective of this study was to examine the role nitrite reductase (gene nirS) plays in P. aeruginosa survival during co infection with an oral streptococcus, Streptococcus parasanguinis. Inactivation of nirS in both the chronic CF isolate FRD1 and acute wound isolate PAO1 reduced the survival rate of P. aeruginosa when co-cultured with S. parasanguinis. Growth of both mutants was restored when co-cultured with S. parasanguinis that was defective for H2O2 production. Furthermore, the nitrite reductase mutant was unable to kill Drosophila melanogaster during co-infection with S. parasanguinis. Taken together, these results suggest that nitrite reductase plays an important role for survival of P. aeruginosa during co-infection with S. parasanguinis. PMID- 26673784 TI - Ultrasound imaging of the liver and bile ducts - expectations of a clinician. AB - Since diseases of the liver and bile ducts are common, a clinician is faced by the need to implement an appropriate diagnostic process. It is necessary to apply diagnostic methods that enable appropriate assessment of the most common pathologies of the liver, i.e. fibrosis, steatosis and focal lesions, as well as initial assessment of the bile ducts. These goals can be achieved using ultrasound methods based on conventional sonography, contrast-enhanced sonography and elastography. The assessment of fatty liver and bile duct dilatation using ultrasound reaches satisfactory levels of sensitivity and specificity. The usage of contrast agents enables unambiguous differentiation between benign and malignant focal lesions, frequently allowing them to be identified accurately without the assistance of other imaging modalities. Elastography has enabled reliable assessment of liver fibrosis. Its results are comparable to those of the standard method, i.e. liver biopsy. PMID- 26673785 TI - Integrating, summarizing and visualizing GWAS-hits and human diversity with DANCE (Disease-ANCEstry networks). AB - MOTIVATION: The 1000 Genomes Project (1KGP) and thousands of Genome-Wide Association Studies (GWAS) performed during the last years have generated an enormous amount of information that needs to be integrated to better understand the genetic architecture of complex diseases in different populations. This integration is important in areas such as genetics, epidemiology, anthropology, as well as admixture mapping design and GWAS-replications. Network-based approaches that explore the genetic bases of human diseases and traits have not yet incorporated information on genetic diversity among human populations. RESULTS: We propose Disease-ANCEstry networks (DANCE), a graph-based web tool that allows to integrate and visualize information on human complex phenotypes and their GWAS-hits, as well as their risk allele frequencies in different populations. DANCE provides an interactive way to explore the human SNP-Disease Network and its projection, a Disease-Disease Network. With these functionalities, DANCE fills a gap in our ability to handle and understand the knowledge generated by GWAS and 1KGP. We provide a number of case studies that show how DANCE can be used to explore the relationships between human complex diseases, their genetic bases and variability in different human populations. AVAILABILITY AND IMPLEMENTATION: DANCE is freely available at http://ldgh.com.br/dance/ We recommend using DANCE with Mozilla Firefox, Safari, Chrome or Internet Explorer (v9 or v10). CONTACT: gilderlanio@gmail.com or maira.r.rodrigues@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26673786 TI - CD248/Endosialin: A Novel Pericyte Target in Renal Fibrosis. PMID- 26673787 TI - Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial. AB - OBJECTIVE: To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. DESIGN: Crossover trial. SETTING: Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. PARTICIPANTS: 24 healthy volunteers aged <=30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. MAIN OUTCOME MEASURES: The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. RESULTS: All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. CONCLUSION: Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. PMID- 26673789 TI - Taxonomic and functional metagenomic analysis of anodic communities in two pilot scale microbial fuel cells treating different industrial wastewaters. AB - The combined processes of microbial biodegradation accompanied by extracellular electron transfer make microbial fuel cells (MFCs) a promising new technology for cost-effective and sustainable wastewater treatment. Although a number of microbial species that build biofilms on the anode surfaces of operating MFCs have been identified, studies on the metagenomics of entire electrogenic communities are limited. Here we present the results of whole-genome metagenomic analysis of electrochemically active robust anodic microbial communities, and their anaerobic digester (AD) sludge inocula, from two pilot-scale MFC bioreactors fed with different distillery wastewaters operated under ambient conditions in distinct climatic zones. Taxonomic analysis showed that Proteobacteria, Bacteroidetes and Firmicutes were abundant in AD sludge from distinct climatic zones, and constituted the dominant core of the MFC microbiomes. Functional analysis revealed species involved in degradation of organic compounds commonly present in food industry wastewaters. Also, accumulation of methanogenic Archaea was observed in the electrogenic biofilms, suggesting a possibility for simultaneous electricity and biogas recovery from one integrated wastewater treatment system. Finally, we found a range of species within the anode communities possessing the capacity for extracellular electron transfer, both via direct contact and electron shuttles, and show differential distribution of bacterial groups on the carbon cloth and activated carbon granules of the anode surface. Overall, this study provides insights into structural shifts that occur in the transition from an AD sludge to an MFC microbial community and the metabolic potential of electrochemically active microbial populations with wastewater-treating MFCs. PMID- 26673788 TI - BEV-IP: Perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis. AB - BACKGROUND: Selected patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) benefit from cytoreductive surgery (CRS) combined with intraperitoneal chemoperfusion (IPC). However, even after optimal cytoreduction, systemic and locoregional recurrence are common. Perioperative chemotherapy with bevacizumab (BEV) may improve the outcome of these patients. METHODS/DESIGN: The BEV-IP study is a phase II, single-arm, open-label study aimed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC. This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality (primary composite endpoint). Secondary endpoints are treatment completion rate, chemotherapy-related toxicity, pathological response, progression free survival, and overall survival. DISCUSSION: The BEV-IP trial is the first prospective assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and IPC for colorectal peritoneal metastases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02399410 EudraCT number: 2015-001187-19 (registered March 9, 2015). PMID- 26673790 TI - OpenLabNotes--An Electronic Laboratory Notebook Extension for OpenLabFramework. AB - Electronic laboratory notebooks (ELNs) are more accessible and reliable than their paper based alternatives and thus find widespread adoption. While a large number of commercial products is available, small- to mid-sized laboratories can often not afford the costs or are concerned about the longevity of the providers. Turning towards free alternatives, however, raises questions about data protection, which are not sufficiently addressed by available solutions. To serve as legal documents, ELNs must prevent scientific fraud through technical means such as digital signatures. It would also be advantageous if an ELN was integrated with a laboratory information management system to allow for a comprehensive documentation of experimental work including the location of samples that were used in a particular experiment. Here, we present OpenLabNotes, which adds state-of-the-art ELN capabilities to OpenLabFramework, a powerful and flexible laboratory information management system. In contrast to comparable solutions, it allows to protect the intellectual property of its users by offering data protection with digital signatures. OpenLabNotes effectively closes the gap between research documentation and sample management, thus making Open LabFramework more attractive for laboratories that seek to increase productivity through electronic data management. PMID- 26673791 TI - RetroMine, or how to provide in-depth retrospective studies from Medline in a glance: the hepcidin use-case. AB - The rapid expansion of biomedical literature has provoked an increased development of advanced text mining tools to rapidly extract relevant events from the continuously increasing amount of knowledge published periodically in PubMed. However, bioinvestigators are still reluctant to use these tools for two reasons: i) a large volume of events is often extracted upon a query, and this volume is hard to manage, and ii) background events dominate search results and overshadow more pertinent published information, especially for domain experts. In this paper, we propose an approach that incorporates the temporal dimension of published events to the process of information extraction to improve data selection and prioritize more pertinent periodically published knowledge for scientists. Indeed, instead of providing the total knowledge associated with a PubMed query, which is usually a mix of trivial background information and non background information, we propose a method that incorporates time and selects non background and highly relevant biological entities and events published over time for bioinvestigators. Before excluding background events from the total knowledge extracted, a quantification of their amount is also provided. This work is illustrated by a case study regarding Hepcidin gene publications over a decade, a duration that is sufficiently long enough to generate alternative views on the overall data extracted. PMID- 26673792 TI - Machine Learning approach to discriminate Saccharomyces cerevisiae yeast cells using sophisticated image features. AB - In biological research, Saccharomyces cerevisiae yeast cells are used to study the behaviour of proteins. This is a time consuming and not completely objective process. Hence, Image analysis platforms are developed to address these problems and to offer analysis per cell as well. The robust segmentation algorithms implemented in such platforms enables us to apply a machine learning approach on the measured cells. Such approach is based on a set of relevant individual cell features extracted from the microscope images of the yeast cells. In this paper, we composed a set of features to represent the intensity and morphology characteristics in a more sophisticated way. These features are based on first and second order histograms and wavelet-based texture measurement. To show the discrimination power of these features, we built a classification model to discriminate between different groups. The building process involved evaluation of a set of classification systems, data sampling techniques, data normalization schemes and attribute selection algorithms. The results show a significant ability to discriminate different cell strains and conditions; subsequently it reveals the benefits of the classification model based on the introduced features. This model is promising in revealing subtle patterns in future high throughput yeast studies. PMID- 26673793 TI - Managing and Documenting Legacy Scientific Workflows. AB - Scientific legacy workflows are often developed over many years, poorly documented and implemented with scripting languages. In the context of our cross disciplinary projects we face the problem of maintaining such scientific workflows. This paper presents the Workflow Instrumentation for Structure Extraction (WISE) method used to process several ad-hoc legacy workflows written in Python and automatically produce their workflow structural skeleton. Unlike many existing methods, WISE does not assume input workflows to be preprocessed in a known workflow formalism. It is also able to identify and analyze calls to external tools. We present the method and report its results on several scientific workflows. PMID- 26673795 TI - Taxonomic Revision of Pinus fujiii (Yasui) Miki (Pinaceae) and Its Implications for the Phytogeography of the Section Trifoliae in East Asia. AB - Pinus trifolia Miki 1939 (Pinaceae) was originally proposed based on seed cones from the upper Miocene of Aichi and Gifu Prefectures, central Japan. However, before the publication of P. trifolia, a different name (Pinus fujiii (Yasui) Miki) was given to a female cone with the same morphology. On the other hand, P. fujiii auct. non (Yasui) Miki has been used for seed cones with different morphologies from Yasui's holotype, i.e., apophyses arranged in 5:8 parastichies and a perexcentromucronate slightly-pointed umbo. As a result of re-examination on the Miki and Yasui specimens, we concluded that P. trifolia was a synonym for P. fujiii and proposed here Pinus mikii sp. nov. for cones assigned to P. fujiii auct. non (Yasui) Miki. We also emended the diagnosis of P. fujiii based on these specimens. Pinus fujiii is characterized by a large female cone in which the apophyses with a centromucronate prickle-like umbo are arranged in 8:13 parastichies, and deciduous seed wings. These characters suggest that P. fujiii belongs to the section Trifoliae of the subgenus Pinus, which is now restricted to North and Central America and the Caribbean islands. Fossil data suggest that the P. fujiii lineage firstly appeared in Japan around the Eocene/Oligocene boundary. We speculate that the P. fujiii lineage might have moved southward to Japan from a refugium located elsewhere in high-latitude areas in response to the late Eocene cooling event, as occurred with other Trifoliae species in North America. PMID- 26673796 TI - Extreme Light Management in Mesoporous Wood Cellulose Paper for Optoelectronics. AB - Wood fibers possess natural unique hierarchical and mesoporous structures that enable a variety of new applications beyond their traditional use. We dramatically modulate the propagation of light through random network of wood fibers. A highly transparent and clear paper with transmittance >90% and haze <1.0% applicable for high-definition displays is achieved. By altering the morphology of the same wood fibers that form the paper, highly transparent and hazy paper targeted for other applications such as solar cell and antiglare coating with transmittance >90% and haze >90% is also achieved. A thorough investigation of the relation between the mesoporous structure and the optical properties in transparent paper was conducted, including full-spectrum optical simulations. We demonstrate commercially competitive multitouch touch screen with clear paper as a replacement for plastic substrates, which shows excellent process compatibility and comparable device performance for commercial applications. Transparent cellulose paper with tunable optical properties is an emerging photonic material that will realize a range of much improved flexible electronics, photonics, and optoelectronics. PMID- 26673794 TI - Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors. AB - BACKGROUND: The capacity for plasticity in the adult brain is limited by the anatomical traces laid down during early postnatal life. Removing certain molecular brakes, such as histone deacetylases (HDACs), has proven to be effective in recapitulating juvenile plasticity in the mature visual cortex (V1). We investigated the chromatin structure and transcriptional control by genome wide sequencing of DNase I hypersensitive sites (DHSS) and cap analysis of gene expression (CAGE) libraries after HDAC inhibition by valproic acid (VPA) in adult V1. RESULTS: We found that VPA reliably reactivates the critical period plasticity and induces a dramatic change of chromatin organization in V1 yielding significantly greater accessibility distant from promoters, including at enhancer regions. VPA also induces nucleosome eviction specifically from retrotransposon (in particular SINE) elements. The transiently accessible SINE elements overlap with transcription factor-binding sites of the Fox family. Mapping of transcription start site activity using CAGE revealed transcription of epigenetic and neural plasticity-regulating genes following VPA treatment, which may help to re-program the genomic landscape and reactivate plasticity in the adult cortex. CONCLUSIONS: Treatment with HDAC inhibitors increases accessibility to enhancers and repetitive elements underlying brain-specific gene expression and reactivation of visual cortical plasticity. PMID- 26673797 TI - The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study. AB - PURPOSE: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer. EXPERIMENTAL DESIGN: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries. RESULTS: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78-2.84; P < 0.0001] and 2.24 (95% CI, 1.75-2.86; P < 0.0001) for the training and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving and not receiving adjuvant antineoplastic therapy. However, in the validation set, the prognostic effect of the marker vanished when looking at patients who received adjuvant antineoplatic therapy (HR 0.90; 95% CI, 0.42-1.93) but was still present in the group not receiving adjuvant chemotherapy (HR 2.88; 95% CI, 1.98-4.21). CONCLUSIONS: The results indicate clinical validity of type IV collagen as a prognostic biomarker in colorectal cancer, although the suggested predictive role of the marker should be validated. Clin Cancer Res; 22(10); 2427-34. (c)2015 AACR. PMID- 26673798 TI - Late Pseudoprogression in Glioblastoma: Diagnostic Value of Dynamic O-(2 [18F]fluoroethyl)-L-Tyrosine PET. AB - PURPOSE: Pseudoprogression (PsP) is characterized by therapy-associated but not tumor growth-associated increases of contrast-enhancing glioblastoma lesions on MRI. Although typically occurring during the first 3 months after radiochemotherapy, PsP may occur later in the course of the disease and may then be particularly difficult to distinguish from true tumor progression. We explored PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET-PET) to approach the diagnostic dilemma. EXPERIMENTAL DESIGN: Twenty-six patients with glioblastoma that presented with increasing contrast-enhancing lesions later than 3 months after completion of radiochemotherapy underwent (18)F-FET-PET. Maximum and mean tumor/brain ratios (TBRmax and TBRmean) of (18)F-FET uptake as well as time-to peak (TTP) and patterns of the time-activity curves were determined. The final diagnosis of true progression versus late PsP was based on follow-up MRI using RANO criteria. RESULTS: Late PsP occurred in 7 patients with a median time from radiochemotherapy completion of 24 weeks while the remaining patients showed true tumor progression. TBRmax and TBRmean were significantly higher in patients with true progression than in patients with late PsP (TBRmax 2.4 +/- 0.1 vs. 1.5 +/- 0.2, P = 0.003; TBRmean 2.1 +/- 0.1 vs. 1.5 +/- 0.2, P = 0.012) whereas TTP was significantly shorter (mean TTP 25 +/- 2 vs. 40 +/- 2 min, P < 0.001). ROC analysis yielded an optimal cutoff value of 1.9 for TBRmax to differentiate between true progression and late PsP (sensitivity 84%, specificity 86%, accuracy 85%, P = 0.015). CONCLUSIONS: O-(2-[(18)F]fluoroethyl)-L-tyrosine PET provides valuable information in assessing the elusive phenomenon of late PsP. Clin Cancer Res; 22(9); 2190-6. (c)2015 AACR. PMID- 26673799 TI - Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. AB - PURPOSE: To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: We established 12 PDXs from BRAF inhibitor-progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and reverse-phase protein arrays. By using multi-arm preclinical trial designs, we identified efficacious precision medicine approaches. RESULTS: We identified alterations previously described as drivers of resistance: NRAS mutations in 3 PDXs, MAP2K1 (MEK1) mutations in 2, BRAF amplification in 4, and aberrant PTEN in 7. At the protein level, re-activation of phospho-MAPK predominated, with parallel activation of PI3K in a subset. Second-line efficacy of the pan-PI3K inhibitor BKM120 with either BRAF (encorafenib)/MEK (binimetinib) inhibitor combination or the ERK inhibitor VX-11e was confirmed in vivo Amplification of MET was observed in 3 PDX models, a higher frequency than expected and a possible novel mechanism of resistance. Importantly, MET amplification alone did not predict sensitivity to the MET inhibitor capmatinib. In contrast, capmatinib as single agent resulted in significant but transient tumor regression in a PDX with resistance to BRAF/MEK combination therapy and high pMET. The triple combination capmatinib/encorafenib/binimetinib resulted in complete and sustained tumor regression in all animals. CONCLUSIONS: Genomic and proteomic data integration identifies dual-core pathway inhibition as well as MET as combinatorial targets. These studies provide evidence for biomarker development to appropriately select personalized therapies of patients and avoid treatment failures. See related commentary by Hartsough and Aplin, p. 1550. PMID- 26673802 TI - Evaluation of weight-adjusted doses of palonosetron for prevention of postoperative nausea and vomiting in day care laparoscopic gynaecological surgery: A dose ranging, randomised controlled trial. AB - BACKGROUND: Palonosetron 75 mcg is being used for the prevention of postoperative nausea and vomiting. However, weight-adjusted doses in laparoscopic surgery are unevaluated. AIM: To determine the response to three doses of palonosetron (0.5, 1.0, or 1.5 mcg kg-1) over 72 h in the postoperative period in women undergoing laparoscopic gynaecological procedures. DESIGN: A randomised dose-response study. SETTING: A tertiary care hospital and research institute in north India from July to December 2014. PATIENTS: American society of Anesthesiologists physical status I and II women, from 18 to 60 years old, undergoing laparoscopic gynaecological procedures on a day care basis. METHODS: Patients were randomised to receive palonosetron 0.5, 1 and 1.5 mcg kg-1 intravenously before induction of anaesthesia. MAIN OUTCOMES MEASURES: The primary outcome was the proportion of patients with a complete response (i.e. who neither vomited nor required additional antiemetic drugs for nausea during the first 72 postoperative hours). The proportion of patients having nausea or emetic episodes and the requirement for rescue antiemetics and analgesics during the 72-h period were recorded as secondary outcomes. RESULTS: With palonosetron, there was a significant dose dependent increase (37.5 vs. 67.5 vs. 75%, P < 0.001) in proportion of patients with a complete response during the 72 h. This was associated with a significant dose-dependent decrease in the proportion of patients with nausea (77.5 vs. 47.5 vs. 35%, P < 0.001) and vomiting (47.5 vs. 32.5 vs. 12.5%, P = 0.003). CONCLUSION: Following laparoscopic gynaecological surgery, intravenous palonosetron has a dose-dependent prophylactic effect against postoperative nausea and vomiting during the first 72 postoperative hours. TRIAL REGISTRATION: The trial was registered with Clinical trial registry of India(CTRI/2014/09/004987). PMID- 26673800 TI - A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer. AB - PURPOSE: Rearranged ROS1 is a crizotinib-sensitive oncogenic driver in lung cancer. The development of acquired resistance, however, poses a serious clinical challenge. Consequently, experimental and clinical validation of resistance mechanisms and potential second-line therapies is essential. EXPERIMENTAL DESIGN: We report the discovery of a novel, solvent-front ROS1(D2033N) mutation in a patient with CD74-ROS1-rearranged lung adenocarcinoma and acquired resistance to crizotinib. Crizotinib resistance of CD74-ROS1(D2033N) was functionally evaluated using cell-based assays and structural modeling. RESULTS: In biochemical and cell based assays, the CD74-ROS1(D2033N) mutant demonstrated significantly decreased sensitivity to crizotinib. Molecular dynamics simulation revealed compromised crizotinib binding due to drastic changes in the electrostatic interaction between the D2033 residue and crizotinib and reorientation of neighboring residues. In contrast, cabozantinib binding was unaffected by the D2033N substitution, and inhibitory potency against the mutant was retained. Notably, cabozantinib treatment resulted in a rapid clinical and near-complete radiographic response in this patient. CONCLUSIONS: These results provide the first example of successful therapeutic intervention with targeted therapy to overcome crizotinib resistance in a ROS1-rearranged cancer. Clin Cancer Res; 22(10); 2351-8. (c)2015 AACR. PMID- 26673801 TI - Hormetic Responses of Food-Supplied Pcb 31 to Zebrafish (Danio Rerio) Growth. AB - Hormesis is commonly defined as a beneficial or stimulatory effect caused by exposure to low doses of a chemical known to be toxic at high doses. Hormetic responses of food-supplied PCB 31 (2, 4', 5-Trichlorobiphenyl) was studied by using zebrafish (Danio rerio) growth as an end point. The results in general followed the hormesis hypothesis, PCB 31 at lower concentrations (0.042 MUg/g and 0.084 MUg/g) exhibited beneficial effects on the growth of zebrafish by weight and length while higher concentrations (10MUg/g and 20MUg/g) revealed inhibitory effects. The magnitude of stimulatory responses of zebrafish growth by weight and length at lower concentrations (0.01-0.084 MUg/g) on days 14 and 21 were in the range 9.09-18.18%; 10-38.09% and 4-14.4%; 6.25-10.93%, respectively as compared to control. Growth and conditions indices also suggested that the zebrafish was healthier at lower concentrations as compared to those at higher concentrations. The results of the present study will elaborate fish toxicological evaluation regarding the hormetic model. PMID- 26673803 TI - Reply to: preventing hypoxia. PMID- 26673804 TI - The assessment of usefulness of the qualification card and ultrasonographic consultation. AB - The result of therapeutic success is always the effect of medical professionals cooperation. The creation of adequate mechanisms of cooperation of these teams demands time and appropriate examples. In the understanding of differentiated behaviors in the line patient - diagnostician - surgeon, particularly the mechanism of the cascade of errors formation, giving simple examples may help - their awareness will facilitate the formation of an adequate pattern of diagnostic-therapeutic chain. The therapeutic team formed in this way provides optimal forms of cooperation and positive result. One of the elements of the cooperation is the surgical procedure qualification card which is an example of the communication between surgeon and diagnostician. The propagation of proven examples seems to be justified by practical reasons. The introduction of the surgical procedure qualification card enabled maintaining of the preoperative and postoperative diagnoses in the range from 88.4% to 89.29%, the barrier of 90% however is still not achieved. The diagnoses discrepancy is still the most often occurring patient safety incident and our results should head towards its mineralization. In particularly complicated cases we come back to a well-known form of medical consultation, that is the form of examination and treatment establishment basing on simultaneous physical and ultrasound examination - hence the colloquial name of ultrasound consultation. The universality of medical consultation makes out of it an excellent tool, particularly in cases of significant discrepancy between physical and ultrasound examination. This is excellent form of the experience exchange and learning about mutual possibilities. We believe that the mechanisms presented will influence the improvement of patient security. PMID- 26673805 TI - Application of ultrasound examination in tactical conditions illustrated with an example of the Field Hospital of the Polish Military Contingent in Afghanistan. AB - It is assumed that tactical medicine encompasses all therapeutic activities performed by a military medical service during military and humanitarian missions. Its scope is only apparently limited by the standards which, when referred to the NATO member countries, have been collected in the Joint Theater Trauma System - Clinical Practice Guidelines. The stage-structured character of medical assistance and treatment of the wounded, injured and sick patients assumes that the scope of therapeutic activities performed at each stage is limited only to essential actions. Consequently, more injured patients may be saved - those for whom life-saving activities are performed prior to their transfer to a higher level. The second level is represented by a field hospital. Its first structure is the trauma room in which a rescue team saves and qualifies the injured for further medical activities. Each injured patient undergoes an eFAST ultrasound examination which allows for a quick decision about a surgical treatment to be provided. Moreover, this technique is helpful in vascular cannulation. The authors present their own experiences with using an ultrasound examination during the work in the Field Hospital of the Polish Military Contingent in Afghanistan. PMID- 26673806 TI - Long-term survival as a treatment benchmark in melanoma: latest results and clinical implications. AB - Historically, stage III-IV melanoma patients have had few options to achieve long term survival. For patients with stage III disease, surgery alone may be curative for approximately 50%. Adjuvant treatment with a slightly greater impact on relapse-free survival at the cost of substantial toxicity, and studies are ongoing to test the adjuvant benefit of other immunotherapies that appear more active and less toxic in advanced melanoma. Achieving long term survival for stage IV patients had been rare until recently and progress was painfully slow with traditional cytotoxic chemotherapy; review of multiple phase II studies showed universally poor results. Fortunately, since the approval by the US Food and Drug Administration of agents targeting the cytotoxic T lymphocyte antigen-4 (CTLA-4) receptor, as well as those targeting B-raf and mitogen-activated protein kinase kinase (MEK) in the mitogen-activated protein kinase (MAPK) pathway for patients whose melanoma is 'driven' by a BRAF mutation, long-term survival of stage IV melanoma is increasing substantially. Here we review the examples of studies documenting potentially curative approaches to melanoma and propose suggestions for the use of various treatments in achieving this important goal. PMID- 26673807 TI - Standards of the Polish Ultrasound Society - update. The liver, gallbladder and bile ducts examinations. AB - Ultrasonography, which usually constitutes an initial imaging method of the gallbladder, liver and bile ducts diseases, allows for final diagnosis or determines another diagnostic step. The continuously progressing technological advancement forces to broaden the indications for ultrasound diagnostics and enables easier and more precise imaging of the tested structures. Performing the examination in accordance with current standards allows for the optimization of the sensitivity and specificity parameters of ultrasound examinations in the diagnosis of the liver, gallbladder and bile ducts pathologies as well as minimizes the probability of error-making. This article presents a recommended liver, gallbladder and bile ducts ultrasound technique which indicates an optimal positioning of the patient for the exam as well as the sites of the ultrasound transducer application. Minimum technical parameters of the apparatus have been specified with respect to the requirements of modern ultrasound techniques which enable imaging with the use of contrast agents and elastography. Furthermore, the article proposes a standard exam description containing essential patient-related data and provides required ultrasound evaluation parameters for the tested organs. Attention has been drawn to the appropriate manner of preparing the patient for the examination and the features of the tested structures have been presented. The article also contains a brief description of the liver, gallbladder and bile ducts diseases which are most often diagnosed by ultrasound examinations. Moreover, the use of elastography as well as contrast-enhanced examinations in the diagnostics of fibrosis and focal changes in the liver have been discussed. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011) and updated with reference to the latest findings in pertinent literature. PMID- 26673808 TI - Metastatic Squamous Cell Carcinoma of the Stomach. AB - Primary squamous cell carcinoma of the stomach is very rare. Its pathogenesis is unclear and the treatment strategy is controversial. We report an agressive primary squamous cell carcinoma of the stomach with liver and lung metastases in a 55-year-old man. The patient presented with a 1-month history of abdominal pain, vomiting and weight loss. Abdominal ultrasound revealed multiple liver metastases. Endoscopic examination showed two tumour masses on the fundus of the stomach. Biopsy of the lesions revealed squamous cell carcinoma of the stomach. Chest x-ray showed multiple large pulmonary nodules highly suggestive of pulmonary metastases. The patient died ten days after he was admitted because of progression of the tumour and before any therapeutic decision. PMID- 26673809 TI - ISO 12189 standard for the preclinical evaluation of posterior spinal stabilization devices--II: A parametric comparative study. AB - The International Standardization Organization (ISO) 12189 standard was recently introduced to preclinically evaluate and compare the mechanical properties of posterior stabilization devices. This scenario presents some new significant steps ahead over the vertebrectomy model recommended by American Society for Testing and Materials (ASTM) F1717 standard: the modular anterior support allows for describing a closer scenario to the effective clinical use as well as to test very flexible and dynamic posterior stabilization devices. Despite these significant advantages, ISO 12189 received little attention in the literature. Anatomical parameters depending on the spinal level were compared to the published data or original measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing the test set-up design, were considered and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by also considering their worst-case combination. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The parametric comparative analysis demonstrates a significant (even beyond +350%) maximum increase in the stress on the device, compared to the standard currently in use. The anterior support stiffness plays the most detrimental effect (maximum stress increases up to 396%). The initial precompression step has an important role in determining the final stress values achieved at peak load (up to +76%). Moreover, when combining these two contributions, an even higher stress increase may be achieved (up to 473%). Despite the other anatomical parameters playing a secondary role, their worst-case combination demonstrates that a device could potentially undergo higher stresses than those reached according to standard suggestions (maximum increase of 22.4% at L1). Any user/designer should be aware of these effects when using ISO 12189 standard for the preclinical evaluation of posterior spinal stabilization devices. PMID- 26673810 TI - Norovirus mechanisms of immune antagonism. AB - Noroviruses are a leading cause of gastroenteritis outbreaks globally. Several lines of evidence indicate that noroviruses can antagonize or evade host immune responses, including the absence of long-lasting immunity elicited during a primary norovirus exposure and the ability of noroviruses to establish prolonged infections that are associated with protracted viral shedding. Specific norovirus proteins possessing immune antagonist activity have been described in recent years although mechanistic insight in most cases is limited. In this review, we discuss these emerging strategies used by noroviruses to subvert the immune response, including the actions of two nonstructural proteins (p48 and p22) to impair cellular protein trafficking and secretory pathways; the ability of the VF1 protein to inhibit cytokine induction; and the ability of the minor structural protein VP2 to regulate antigen presentation. We also discuss the current state of the understanding of host and viral factors regulating the establishment of persistent norovirus infections along the gastrointestinal tract. A more detailed understanding of immune antagonism by pathogenic viruses will inform prevention and treatment of disease. PMID- 26673812 TI - Ibrutinib--a new standard treatment for relapsed mantle cell lymphoma? PMID- 26673811 TI - Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. AB - BACKGROUND: Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. METHODS: This randomised, open label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). FINDINGS: Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0.0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0.43 [95% CI 0.32-0.58]; median progression-free survival 14.6 months [95% CI 10.4-not estimable] vs 6.2 months [4.2-7.9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). INTERPRETATION: Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. FUNDING: Janssen Research & Development, LLC. PMID- 26673813 TI - Metal-Support Interactions of Platinum Nanoparticles Decorated N-Doped Carbon Nanofibers for the Oxygen Reduction Reaction. AB - N-doped carbon materials are discussed as catalyst supports for the electrochemical oxygen reduction reaction (ORR) in fuel cells. This work deals with the preparation of Pt nanoparticles (NPs) supported on N-doped carbon nanofibers (N-CNF) from a polyaniline nanofiber (PANI NF) precursor, and investigates the ORR activity of the produced materials. Initially, Pt NPs are deposited on PANI NFs. The PANI NF precursors are characterized by near-edge X ray absorption fine structure (NEXAFS) and transmission electron microscopy (TEM) measurements. It is shown, that in the PANI NF precursor materials electrons from the Pt are being transferred toward the pi-conjugated systems of the aromatic ring. This strong interaction of Pt atoms with PANI explains the high dispersion of Pt NPs on the PANI NF. Subsequently, the PANI NF precursors are carbonized at different heat-treatment conditions resulting in structurally different N-CNFs which are characterized by NEXAFS, X-ray photoelectron spectroscopy (XPS) ,and TEM measurements. It is shown that an interaction between N-groups and Pt NPs exists in all investigated N-CNFs. However, the N-CNFs differ in the composition of the N-species and the dispersion of the Pt NPs. A small mean Pt NP size with a narrow size distribution is attributed to the presence of pyrdinic N-groups in the N-CNFs, whereas, for the N-CNFs with mainly graphitic and pyrrolic N-groups, an increase in the average Pt NP size with a broad size distribution is found. The ORR activity in alkaline media investigated by Koutecky-Levich analysis of rotating disk electrode measurements showed a largely enhanced ORR activity in comparison to a conventional Pt/C catalyst. PMID- 26673815 TI - A home-based comprehensive care model in patients with Multiple Sclerosis: A study pre-protocol. AB - Background Disability is prevalent in individuals with multiple sclerosis (MS), leading to difficulty in care access, significant caregiver burden, immense challenges in self-care and great societal burden. Without highly coordinated, competent and accessible care, individuals living with progressive MS experience psychological distress, poor quality of life, suffer from life-threatening complications, and have frequent but avoidable healthcare utilizations. Unfortunately, current healthcare delivery models present severe limitations in providing easily accessible, patient-centered, coordinated comprehensive care to those with progressive MS. We propose a home-based comprehensive care model (MAHA) to address the unmet needs, challenges, and avoidable complications in individuals with progressive MS with disabling disease. Objective The article aims to describe the study design and methods used to implement and evaluate the proposed intervention. Method The study will use a randomized controlled design to evaluate the feasibility of providing a 24-month, home-based, patient-centered comprehensive care program to improve quality of life, reduce complications and healthcare utilizations overtime (quarterly) for 24 months. A transdisciplinary team led by a MS-Comprehensivist will carry out this project. Fifty MS patients will be randomly assigned to the intervention and usual care program using block randomization procedures. We hypothesize that patients in the intervention group will have fewer complications, higher quality of life, greater satisfaction with care, and reduced healthcare utilization. The proposed project is also expected to be financially sustainable in fee-for-service models but best suited for and gain financial success in valued-based care systems. Discussion This is the first study to examine the feasibility and effectiveness of a home-based comprehensive care management program in MS patients living with progressive disability. If successful, it will have far-reaching implications in research, education and practice in terms of providing high quality but affordable care to population living with severe complex, disabling conditions. PMID- 26673814 TI - Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans. AB - OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE epsilon4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia. PMID- 26673817 TI - Adrenal insufficiency due to the development of bilateral adrenal haemorrhage following hip replacement surgery. AB - Bilateral adrenal haemorrhage should be considered as a differential diagnosis in patients presenting with non-specific symptoms and hypotension postoperatively. PMID- 26673816 TI - Ternary structure reveals mechanism of a membrane diacylglycerol kinase. AB - Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The gamma phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution. PMID- 26673818 TI - A versatile ex vivo technique for assaying tumor angiogenesis and microglia in the brain. AB - Primary brain tumors are hallmarked for their destructive activity on the microenvironment and vasculature. However, solely few experimental techniques exist to access the tumor microenvironment under anatomical intact conditions with remaining cellular and extracellular composition. Here, we detail an ex vivo vascular glioma impact method (VOGIM) to investigate the influence of gliomas and chemotherapeutics on the tumor microenvironment and angiogenesis under conditions that closely resemble the in vivo situation. We generated organotypic brain slice cultures from rats and transgenic mice and implanted glioma cells expressing fluorescent reporter proteins. In the VOGIM, tumor-induced vessels presented the whole range of vascular pathologies and tumor zones as found in human primary brain tumor specimens. In contrast, non-transformed cells such as primary astrocytes do not alter the vessel architecture. Vascular characteristics with vessel branching, junctions and vessel meshes are quantitatively assessable as well as the peritumoral zone. In particular, the VOGIM resembles the brain tumor microenvironment with alterations of neurons, microglia and cell survival. Hence, this method allows live cell monitoring of virtually any fluorescence-reporter expressing cell. We further analyzed the vasculature and microglia under the influence of tumor cells and chemotherapeutics such as Temozolamide (Temodal/Temcad(r)). Noteworthy, temozolomide normalized vasculare junctions and branches as well as microglial distribution in tumor-implanted brains. Moreover, VOGIM can be facilitated for implementing the 3Rs in experimentations. In summary, the VOGIM represents a versatile and robust technique which allows the assessment of the brain tumor microenvironment with parameters such as angiogenesis, neuronal cell death and microglial activity at the morphological and quantitative level. PMID- 26673819 TI - A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells. AB - All-trans retinoic acid (ATRA) treatment yields cure rates > 80% through proteasomal degradation of the PML-RARalpha fusion protein that typically promotes acute promyelocytic leukemia (APL). However, recent evidence indicates that ATRA can also promote differentiation of leukemia cells that are PML RARalpha negative, such as HL-60 cells. Here, gene expression profiling of HL-60 cells was used to investigate the alternative mechanism of impaired differentiation in APL. The expression of peptidylarginine deiminase 4 (PADI4), encoding PAD4, a protein that post-translationally converts arginine into citrulline, was restored during ATRA-induced differentiation. We further identified that hypermethylation in the PADI4 promoter was associated with its transcriptional repression in HL-60 and NB4 (PML-RARalpha positive) cells. Functionally, PAD4 translocated into the nucleus upon ATRA exposure and promoted ATRA-mediated differentiation. Mechanistic studies using RNAi knockdown or electroporation-mediated delivery of PADI4, along with chromatin immunoprecipitation, helped identify PU.1 as an indirect target and SOX4 as a direct target of PAD4 regulation. Indeed, PAD4 regulates SOX4-mediated PU.1 expression, and thereby the differentiation process, in a SOX4-dependent manner. Taken together, our results highlight an association between PAD4 and DNA hypermethylation in APL and demonstrate that targeting PAD4 or regulating its downstream effectors may be a promising strategy to control differentiation in the clinic. PMID- 26673820 TI - Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling. AB - BACKGROUND: Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling. METHODS: CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo responsiveness. RESULTS: EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively. CONCLUSIONS: MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients. PMID- 26673821 TI - UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation. AB - Phosphorylation of p53 is a key mechanism responsible for the activation of its tumor suppressor functions in response to various stresses. In unstressed cells, p53 is rapidly turned over and is maintained at a low basal level. After DNA damage or other forms of cellular stress, the p53 level increases, and the protein becomes metabolically stable. However, the mechanism of phosphorylated p53 regulation is unclear. In this study, we studied the kinetics of UBE4B, Hdm2, Pirh2, Cop1 and CHIP induction in response to p53 activation. We show that UBE4B coimmunoprecipitates with phosphorylated p53 at serines 15 and 392. Notably, the affinity between UBE4B and Hdm2 is greatly decreased after DNA damage. Furthermore, we observe that UBE4B promotes endogenous phospho-p53(S15) and phospho-p53(S392) degradation in response to IR. We demonstrate that UBE4B and Hdm2 repress p53S15A, p53S392A, and p53-2A(S15A, S392A) functions, including p53 dependent transactivation and growth inhibition. Overall, our results reveal that UBE4B plays an important role in regulating phosphorylated p53 following DNA damage. PMID- 26673822 TI - A tyrosine phosphatase SHP2 gain-of-function mutation enhances malignancy of breast carcinoma. AB - BACKGROUND: Evidence suggests that Src homologous protein phosphotyrosyl phosphatase 2 (SHP2) mutations promote cancer development in several solid tumours. In this study, we focused on the in vivo and in vitro effects of an SHP2 mutation on the breast cancer phenotype to determine whether this mutation is correlated with a malignant phenotype. METHODS: Mutant PTPN11 cDNA (D61G) was transduced into MDA-MB231 and MCF-7 cells. The effects of the D61G mutation on tumourigenesis and malignant behaviours, such as cell adhesion, proliferation, migration and invasion, were examined. Potential underlying molecular mechanisms, i.e., activation of the Gab1-Ras-Erk axis, were also examined. RESULTS: In vitro experiments revealed that tumour adhesion, proliferation, migration and invasion were significantly increased in the SHP2 D61G mutant groups. Consistently, in vivo experiments also showed that the tumour sizes and weights were increased significantly in the SHP2 D61G-MB231 group (p < 0.001) in association with tumour metastasis. Mechanistically, the PTPN11 mutation resulted in activation of the Ras-ErK pathway. The binding between Gab1 and mutant SHP2 was significantly increased. CONCLUSION: Mutant SHP2 significantly promotes tumour migration and invasion at least partially through activation of the Gab1-Ras-Erk axis. This finding could have direct implications for breast cancer therapy. PMID- 26673823 TI - Integrative omics reveals MYCN as a global suppressor of cellular signalling and enables network-based therapeutic target discovery in neuroblastoma. AB - Despite intensive study, many mysteries remain about the MYCN oncogene's functions. Here we focus on MYCN's role in neuroblastoma, the most common extracranial childhood cancer. MYCN gene amplification occurs in 20% of cases, but other recurrent somatic mutations are rare. This scarcity of tractable targets has hampered efforts to develop new therapeutic options. We employed a multi-level omics approach to examine MYCN functioning and identify novel therapeutic targets for this largely un-druggable oncogene. We used systems medicine based computational network reconstruction and analysis to integrate a range of omic techniques: sequencing-based transcriptomics, genome-wide chromatin immunoprecipitation, siRNA screening and interaction proteomics, revealing that MYCN controls highly connected networks, with MYCN primarily supressing the activity of network components. MYCN's oncogenic functions are likely independent of its classical heterodimerisation partner, MAX. In particular, MYCN controls its own protein interaction network by transcriptionally regulating its binding partners.Our network-based approach identified vulnerable therapeutically targetable nodes that function as critical regulators or effectors of MYCN in neuroblastoma. These were validated by siRNA knockdown screens, functional studies and patient data. We identified beta-estradiol and MAPK/ERK as having functional cross-talk with MYCN and being novel targetable vulnerabilities of MYCN-amplified neuroblastoma. These results reveal surprising differences between the functioning of endogenous, overexpressed and amplified MYCN, and rationalise how different MYCN dosages can orchestrate cell fate decisions and cancerous outcomes. Importantly, this work describes a systems-level approach to systematically uncovering network based vulnerabilities and therapeutic targets for multifactorial diseases by integrating disparate omic data types. PMID- 26673824 TI - Urinary neutrophil gelatinase-associated lipocalin is associated with heavy metal exposure in welding workers. AB - Metals cause nephrotoxicity with acute and/or chronic exposure; however, few epidemiological studies have examined impacts of exposure to metal fumes on renal injury in welding workers. In total, 66 welding workers and 12 office workers were recruited from a shipyard located in southern Taiwan. Urine samples from each subject were collected at the beginning (baseline) and end of the work week (1-week exposure). Personal exposure to PM2.5 was measured. The 8-h mean PM2.5 was 50.3 MUg/m(3) for welding workers and 27.4 MUg/m(3) for office workers. iTRAQs coupled with LC-MS/MS were used to discover the pathways in response to welding PM2.5 in the urine, suggesting that extracellular matrix (ECM)-receptor interactions are a critical mechanism. ECM-receptor interaction-related biomarkers for renal injury, kidney injury molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL), were significantly elevated in welding workers post-exposure, as well as were urinary Al, Cr, Mn, Fe, Co, and Ni levels. NGAL was more significantly associated with Al (r = 0.737, p < 0.001), Cr (r = 0.705, p < 0.001), Fe (r = 0.709, p < 0.001), and Ni (r = 0.657, p < 0.001) than was KIM-1, suggesting that NGAL may be a urinary biomarker for welding PM2.5 exposure. Nephrotoxicity (e.g., renal tubular injury) may be an emerging concern in occupational health. PMID- 26673825 TI - A roadmap for the XCMS family of software solutions in metabolomics. AB - Global profiling of metabolites in biological samples by liquid chromatography/mass spectrometry results in datasets too large to evaluate manually. Fortunately, a variety of software programs are now available to automate the data analysis. Selection of the appropriate processing solution is dependent upon experimental design. Most metabolomic studies a decade ago had a relatively simple experimental design in which the intensities of compounds were compared between only two sample groups. More recently, however, increasingly sophisticated applications have been pursued. Examples include comparing compound intensities between multiple sample groups and unbiasedly tracking the fate of specific isotopic labels. The latter types of applications have necessitated the development of new software programs, which have introduced additional functionalities that facilitate data analysis. The objective of this review is to provide an overview of the freely available bioinformatic solutions that are either based upon or are compatible with the algorithms in XCMS, which we broadly refer to here as the 'XCMS family' of software. These include CAMERA, credentialing, Warpgroup, metaXCMS, X(13)CMS, and XCMS Online. Together, these informatic technologies can accommodate most cutting-edge metabolomic applications and offer unique advantages when compared to the original XCMS program. PMID- 26673826 TI - Effects of Photobiomodulation Therapy on Patients with Primary Open Angle Glaucoma: A Pilot Study. AB - OBJECTIVE: The purpose of this work was to study the safety of photobiomodulation therapy in patients with primary open angle glaucoma (POAG). BACKGROUND DATA: Therapeutic options for POAG focus on lowering the intraocular pressure (IOP) but cannot stop disease progression to irreversible damages. METHODS: The study was designed as a controlled, single-blinded, interventional case series (38 patients; 63 eyes). Low-level laser therapy was performed once or twice per week using a continuous wave (CW) diode laser (780 nm; 10 mW; 292 Hz modulation; 3 mm(2) beam spot). The limbus area was circularly irradiated for 30 sec (0.3 W/cm(2); 10 J/cm(2)) at a 1 cm distance. Additional parts of the bulbus were irradiated for 90 sec (30 J/cm(2)) pointing the beam toward retinal areas corresponding to defective visual fields. A control group of 10 patients (20 eyes) received mock treatment. Visual acuity was assessed using Snellen projection optotypes. IOP was determined by applanation tonometry. Visual fields were determined by kinetic Goldmann perimetry. Multifocal visual evoked potential (M-VEP) was recorded in 15 patients (30 eyes). RESULTS: Poor visual acuity (<= 20/25), initially found in 24 of 63 eyes (38.1%), improved in 17 (70.8%) eyes and did not change in 7 eyes (29.2%). Mean IOP dropped from 24.9 +/- 14.9 to 15.0 +/- 6.5 mm Hg (-39.7%, p < 0.001). Visual fields were either fully restored, improved by at least 10 degrees, or remained unchanged in 32, 29, and 2 of 63 eyes (51%, 46%, and 3%), respectively. Mean M-VEP latency was reduced by 13.5 msec (-8%, p < 0.001); mean amplitude increased by +677 nV (+14%, p < 0.001). Adverse effects were not observed. No changes were noted in control eyes. CONCLUSIONS: This first small series of cases indicated that photobiomodulation might be a safe approach to lower IOP and to improve visual acuity and fields in eyes with POAG. PMID- 26673827 TI - Quantification of the concentration gradient of biomarkers between ovarian carcinoma interstitial fluid and blood. AB - BACKGROUND: Tumor interstitial fluid (TIF) rather than plasma should be used in cancer biomarker discovery because of the anticipated higher concentration of locally produced proteins in the tumor microenvironment. Nevertheless, the actual TIF-to-plasma gradient of tumor specific proteins has not been quantified. We present the proof-of-concept for the quantification of the postulated gradient between TIF and plasma. METHODS: TIF was collected by centrifugation from serous (n = 19), endometrioid (n = 9) and clear cell (n = 3) ovarian carcinomas with early (n = 15) and late stage (n = 16) disease in grades 1 (n = 2), 2 (n = 8) and 3 (n = 17), and ELISA was used for the determination of CA-125, osteopontin and VEGF-A. RESULTS: All three markers were significantly up-regulated in TIF compared with plasma (p < 0.0001). The TIF-to-plasma ratio of the ovarian cancer biomarker CA-125 ranged from 1.4 to 24,300 (median = 194) and was inversely correlated to stage (p = 0.0006). The cancer related osteopontin and VEGF-A had TIF-to-plasma ratios ranging from 1 to 62 (median = 15) and 2 to 1040 (median = 59), respectively. The ratios were not affected by tumor stage, indicative of more widespread protein expression. CONCLUSION: We present absolute quantitative data on the TIF-to-plasma gradient of selected proteins in the tumor microenvironment, and demonstrate a substantial and stage dependent gradient for CA-125 between TIF and plasma, suggesting a relation between total tumor burden and tissue-to-plasma gradient. GENERAL SIGNIFICANCE: We present novel quantitative data on biomarker concentration in the tumor microenvironment, and a new strategy for biomarker selection, applicable in future biomarker studies. PMID- 26673828 TI - The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part II: Diagnostic value of BIRADS-US classification, Tsukuba score and FLR ratio. AB - Sonoelastography is a dynamically developing method of ultrasound examination used to differentiate the character of focal lesions in the breasts. The aim of the Part II of the study is to determine the usefulness of sonoelastography in the differentiation diagnosis of focal breast lesions including the evaluation of the diagnostic value of Tsukuba score and FLR ratio in characterizing solid lesions in the breasts. Furthermore, the paper provides a comparison of classic B mode imaging and sonoelastography. MATERIAL AND METHODS: From January to July 2010 in the Ultrasound Department of the Cancer Centre, The Institute of Maria Sklodowska-Curie, 375 breast ultrasound examinations were conducted. The examined group included patients who in B-mode examinations presented indications for pathological verification. They were 80 women aged between 17 and 83 (mean age was 50) with 99 solid focal lesions in the breasts. All patients underwent: the interview, physical examination, B-mode ultrasound examination and elastography of the mammary glands and axillary fossae. The visualized lesions were evaluated according to BIRADS-US classification and Tsukuba score as well as FLR ratio was calculated. In all cases, the histopathological and/or cytological verification of the tested lesions was obtained. RESULTS: In the group of 80 patients, the examination revealed 39 malignant neoplastic lesions and 60 benign ones. The mean age of women with malignant neoplasms was 55.07 (SD = 10.54), and with benign lesions - 46.9 (SD = 15.47). In order to identify threshold values that distinguish benign lesions from malignant ones, a comparative analysis of statistical models based on BIRADS-US classification and Tsukuba score was conducted and the cut-off value for FLR was assumed. The sensitivity and specificity values for BIRADS-US 4/5 were 76.92% and 96.67% and for Tsukuba 3/4 - 64.1% and 98.33% respectively. The assumed FLR threshold value to differentiate between benign and malignant lesions in the breasts equaled 3.13. The combined application of both classifications (with the threshold value of BIRADS-US 4/Tsukuba 3) improved the total value of sensitivity and specificity of character differentiation of focal lesions (87.2% and 95% respectively). CONCLUSIONS: In the case of problematic focal lesions, i.e. BIRADS-US 3, the study revealed that obtaining Tsukuba score of 1 and 2 for lesions classified as BIRADS-US 3 confirms their benign character. This allows to avoid the cytological verification. PMID- 26673829 TI - Pilot Study: Survey Tools for Assessing Parenting Styles and Family Contributors to the Development of Obesity in Arab Children Ages 6 to 12 Years. AB - OBJECTIVE: Our pilot study was conducted to test the reliability of the Caregiver's Feeding Styles Questionnaire (CFSQ) and the Family Nutrition and Physical Activity Assessment (FNPA) in a sample of Arab mothers. DESIGN: Twenty five Arab mothers completed the CFSQ, FNPA, and the Participant Background Survey for the first administration. After 1-2 weeks, participants completed the CFSQ and the FNPA for the second administration. The two administrations of the surveys allowed for test/retest reliability of the CFSQ and the FNPA and to measure the internal consistency of the two surveys. RESULTS: Pearson's correlation between the first and second administrations or the 19-item scale (demandingness) and the 7-item scale (responsiveness) of the CFSQ were .95 and .86, respectively. As for the FNPA, Pearson's correlation was .80. The estimated reliabilities (Cronbach's alpha) of the CFSQ increased from .86 for the first administration to .93 for the second administration. However, the estimated reliabilities of the FNPA slightly increased from .58 for first administration to .59 for the second administration. CONCLUSION: In our pilot study of Arab mothers, the CFSQ and FNPA were shown to be promising in terms of reliability and content validity. PMID- 26673830 TI - Impact of T300A Variant of ATG16L1 on Antibacterial Response, Risk of Culture Positive Infections, and Clinical Course of Crohn's Disease. AB - OBJECTIVES: Autophagy-related 16-like 1 (ATG16L1) deficiency leads to impaired cellular autophagy and bacterial degradation as well as an altered cytokine production. The single-nucleotide polymorphism rs2241880 (T300A) is associated with an increased risk for Crohn's disease (CD). ATG16L1 polymorphisms could therefore have an impact on the risk of infectious complications and disease course in CD. We examined the impact of the T300A genotype on the antibacterial response toward a panel of pathogenic bacteria in vitro, as well as clinical infectious complications in vivo and the disease course in a Danish cohort of patients with CD. METHODS: A total of 236 CD patients were genotyped for ATG16L1(T300A); their clinical records were reviewed, and microbial, radiological, and surgical data were scrutinized. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and CD patients carrying the different ATG16L1 genotypes, and the production of tumor necrosis factor (TNF) alpha and interleukin (IL)-1beta was measured by enzyme-linked immunosorbent assay after stimulation with a panel of pathogenic bacteria of clinical relevance for the gastrointestinal tract, e.g., enteroinvasive Escherichia coli (EIEC), Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, or Mycobacterium avium paratuberculosis. RESULTS: Fifty-seven healthy controls (15, 29, 13) and 236 patients with CD (50, 108, 78) were genotyped for the T300A ATG16L1 polymorphism (AA homozygous, GG homozygous risk variant, AG heterozygous variant, respectively). The median duration of disease was 128 months (range, 30 175). The cumulative follow-up of this cohort was 2,366 patient-years. ATG16L1 gene variations interfered with the production of IL-1beta, which was significantly increased in PBMCs from GG patients in response to all tested bacteria, whereas the TNF-alpha production was decreased in PBMCs from GG patients stimulated with EIEC, L. monocytogenes, and S. typhimurium, but unaffected by the other bacteria tested. Moreover, the GG variant showed a nonsignificant increase in the risk of bowel resections (P=0.07) and postsurgical infections (P=0.08), whereas the risk of non-disease-related infections was unaffected by genotype in the observation period. In addition, patients with AA and AG variants had a higher frequency of complicated fistulizing disease (P=0.03) with an overall more aggravated disease course with an increased number of surgical procedures for fistulous disease from a median 6.5 operations (2.0 in GG patients; P=0.002). This risk was independent on disease phenotype (penetrating vs. non-penetrating) and immunomodulating medication. CONCLUSIONS: The T300A variant in patients with CD strongly increases the risk for complicated fistulizing disease, and significantly affects antibacterial responses in vitro, but the latter effect seems to have a minor role for the infectious risk in CD. PMID- 26673831 TI - Capturing Islet Stem Cells for a Bio-Artificial Pancreas. PMID- 26673832 TI - The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part I and II. PMID- 26673833 TI - The Neuroprotective Effect of Dark Chocolate in Monosodium Glutamate-Induced Nontransgenic Alzheimer Disease Model Rats: Biochemical, Behavioral, and Histological Studies. AB - The vulnerability to oxidative stress and cognitive decline continue to increase during both normal and pathological aging. Dietary changes and sedentary life style resulting in mid-life obesity and type 2 diabetes, if left uncorrected, further add to the risk of cognitive decline and Alzheimer disease (AD) in the later stages of life. Certain antioxidant agents such as dietary polyphenols, taken in adequate quantities, have been suggested to improve the cognitive processes. In this study, we examined the effect of oral administration of dark chocolate (DC) containing 70% cocoa solids and 4% total polyphenol content for three months at a dose of 500 mg/Kg body weight per day to 17-month-old monosodium glutamate treated obese Sprague-Dawley rats, earlier characterized as a nontransgenic AD (NTAD) rat model after reversal of obesity, diabetes, and consequent cognitive impairments. The results demonstrated that DC reduced the hyperglycemia, inhibited the cholinesterase activity in the hippocampal tissue homogenates, and improved the cognitive performance in spatial memory related Barnes maze task. Histological studies revealed an increase in cell volume in the DC treated rats in the CA3 region of the hippocampus. These findings demonstrated the benefits of DC in enhancing cognitive function and cholinergic activity in the hippocampus of the aged NTAD rats while correcting their metabolic disturbances. PMID- 26673835 TI - Factors affecting survival following self-inflicted head and neck gunshot wounds: a single-centre retrospective review. AB - Self-inflicted head and neck gunshot wounds are a common modality of suicide in the USA. This study reviewed all self-inflicted head and neck gunshot wound patients with complete records (n=157) treated at a tertiary centre between 2002 and 2012 inclusive. The associations between mortality and patient/clinical variables were evaluated with the chi(2) test or Fisher's exact test for statistical difference testing. Outcomes recorded were death (n=92, 59%), discharge to long-term care/rehabilitation (n=58, 37%), and discharge home (n=7, 4%). The majority of patients were male (86.6%) and single/separated/divorced (55.5%). The mortality rate by site, in descending order, was temporal 82%, frontal scalp 69%, submental/intraoral 30%, and neck 25%. Involvement of the central nervous system (n=127) resulted in a 70% mortality, but a lower mortality was observed among patients with an avulsion injury (P=0.025). A tracheostomy within 24h of admission was statistically associated with improved survival (P<0.001), but confounding factors were found. Multivariate analysis revealed increasing age, temporal entry site, and the severity of central nervous system involvement to be positively associated with an increased mortality. PMID- 26673834 TI - A protein polymerization cascade mediates toxicity of non-pathological human huntingtin in yeast. AB - Several neurodegenerative amyloidoses, including Huntington disease, are caused by expansion of polyglutamine (polyQ) stretches in otherwise unrelated proteins. In a yeast model, an N-terminal fragment of mutant huntingtin with a stretch of 103 glutamine residues aggregates and causes toxicity, while its non-toxic wild type variant with a sequence of 25 glutamines (Htt25Q) does not aggregate. Here, we observed that non-toxic polymers of various proteins with glutamine-rich domains could seed polymerization of Htt25Q, which caused toxicity by seeding polymerization of the glutamine/asparagine-rich Sup35 protein thus depleting the soluble pools of this protein and its interacting partner, Sup45. Importantly, only polymers of Htt25Q, but not of the initial benign polymers, induced Sup35 polymerization, indicating an intermediary role of Htt25Q in cross-seeding Sup35 polymerization. These data provide a novel insight into interactions between amyloidogenic proteins and suggest a possible role for these interactions in the pathogenesis of Huntington and other polyQ diseases. PMID- 26673836 TI - Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins. AB - Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures. PMID- 26673837 TI - Bilateral Calcifying Cystic Odontogenic Tumour of Mandible: A Rare Case Report and Review of Literature. AB - Calcifying cystic odontogenic tumour (CCOT) is a relatively rare lesion of oral and maxillofacial region and forms only 2% of all odontogenic tumours. It was previously known as Calcifying odontogenic cyst and only recently has been classified as a tumour by WHO. The controversy regarding its origin can be owed to its diverse clinical and histopathological presentation and variation in reported malignant potential. It was first reported by Gorlin in 1962 and since then conundrum regarding its true nature has persisted. It is seen in association with other lesions like odontoma, ameloblastoma and ameloblastic fibroma. Both intra-osseous and extra-osseous forms of CCOT have been reported. It commnoly occurs in anterior region with equal preponderance in maxilla and mandible. Here we present a rare case of bilateral CCOT in the posterior mandible of a 16-year old male patient which was discovered incidentally during a radiographic examination. PMID- 26673838 TI - Analysis of qualitative data from the investigation study in pregnancy of the ASSIST Version 3.0 (the Alcohol, Smoking and Substance Involvement Screening Test). AB - OBJECTIVE: to utilise qualitative data from investigation of the screening tool ASSIST Version 3.0 with pregnant women to help determine its appropriateness for this cohort, thus informing potential innovations to enhance the questionnaire's utility. DESIGN: pregnant women were co-administered the ASSIST Version 3.0 and three established substance use questionnaires (the T-ACE for alcohol, the Timeline FollowBack for cannabis and the Revised Fagerstrom Questionnaire for tobacco). SETTING: antenatal clinics and the antenatal ward of the Women's and Children's Hospital, Adelaide, South Australia. PARTICIPANTS: 104 pregnant substance-users. MEASUREMENTS AND FINDINGS: as well as the quantitative date (reported elsewhere), rich qualitative data documenting participants' perspectives and experiences in antenatal care were thematically analysed. Women constantly reported friends and family urging them to stop use. Although care providers also advocated cessation or curtailment of use, this advice was reported as unpredictable, with only some providers strongly attuned to such recommendations. Some women voiced suggestions for the appropriate level of provider advice. While pregnancy was often reported as a motivator for changing substance-using behaviour, others reported continued attachment to use which was clearly linked to dependence. Those who reported successful control of use were in contrast to others who were more pragmatic, sceptical in relation to attributable harms, and disinterested in change. There were limited reports of experiences of discrimination directed to pregnant substance users. However, those instances were clearly linked with subsequent lack of honest discussions with care providers, resulting in an absence of appropriate support. KEY CONCLUSIONS: current absence of universal screening for substance use has the potential for less than optimal consequences for both mother and baby. IMPLICATIONS FOR PRACTICE: appropriate screening accompanied by honest, non judgmental dialogue can guide the necessary interventions to achieve better outcomes. The recent development of the more concise and easier to administer ASSIST-LITE was partly informed by this investigation. PMID- 26673839 TI - Psychological changes in alcohol-dependent patients during a residential rehabilitation program. AB - BACKGROUND: Alcohol-dependent patients usually experience negative affects under the influence of alcohol, and these affective symptoms have been shown to decrease as a result of alcohol-withdrawal treatment. A recent cognitive affective model suggests an interaction between drug motivation and affective symptoms. The aim of this multicenter study was to evaluate the psychological changes in subjects undergoing a residential rehabilitation program specifically designed for alcohol addiction, and to identify at discharge patients with greater affective symptoms and therefore more at risk of relapse. MATERIALS AND METHODS: The sample included 560 subjects (mean age 46.91+/-10.2 years) who completed 28-day rehabilitation programs for alcohol addiction, following a tailored routine characterized by short duration and high intensity of medical and psychotherapeutic treatment. The psychological clinical profiles of anxiety, depression, psychological distress, psychological well-being, and self-perception of a positive change were assessed using the Cognitive Behavioral Assessment - Outcome Evaluation questionnaire at the beginning and at the end of the program. The changes in the psychological variables of the questionnaire were identified and considered as outcome evaluation of the residential intervention. Moreover, differences in the psychological functioning between patients with different characteristics were investigated. RESULTS: The score measured by the Cognitive Behavioral Assessment - Outcome Evaluation showed significant improvements in all the psychological characteristics assessed, and the profile at discharge was within the normal scores. Some significant differences were found in relation to specific characteristics of the sample, such as age, sex, level of education, type of intervention, and polysubstance use. CONCLUSION: This study shows the changes in psychological profile in subjects undergoing residential rehabilitation from alcohol and how this profile may permit identification of subjects requiring more psychosocial support after discharge. PMID- 26673840 TI - Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury--Results From an Automated Data Collection System Time-Synched to Drug Administration. AB - OBJECTIVES: To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury. Currently, data supporting the efficacy of these medications are insufficient. DESIGN: In this prospective observational study, intracranial hypertension (intracranial pressure >= 20 mm Hg for > 5 min) was treated by clinical protocol. Administration times of medications for intracranial hypertension (fentanyl, 3% hypertonic saline, mannitol, and pentobarbital) were prospectively recorded and synchronized with an automated database that collected intracranial pressure and cerebral perfusion pressure every 5 seconds. Intracranial pressure crises confounded by external stimulation or mechanical ventilator adjustments were excluded. Mean intracranial pressure and cerebral perfusion pressure from epochs following drug administration were compared with baseline values using Kruskal-Wallis analysis of variance and Dunn test. Frailty modeling was used to analyze the time to intracranial pressure crisis resolution. Mixed-effect models compared intracranial pressure and cerebral perfusion pressure 5 minutes after the medication versus baseline and rates of treatment failure. SETTING: A tertiary care children's hospital. PATIENTS: Children with severe traumatic brain injury (Glasgow Coma Scale score <= 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 196 doses of fentanyl, hypertonic saline, mannitol, and pentobarbital administered to 16 children (median: 12 doses per patient). Overall, intracranial pressure significantly decreased following the administration of fentanyl, hypertonic saline, and pentobarbital. After controlling for administration of multiple medications, intracranial pressure was decreased following hypertonic saline and pentobarbital administration; cerebral perfusion pressure was decreased following fentanyl and was increased following hypertonic saline administration. After adjusting for significant covariates (including age, Glasgow Coma Scale score, and intracranial pressure), hypertonic saline was associated with a two-fold faster resolution of intracranial hypertension than either fentanyl or pentobarbital. Fentanyl was significantly associated with the most frequent treatment failure. CONCLUSIONS: Intracranial pressure decreased after multiple drug administrations, but hypertonic saline may warrant consideration as the first-line drug for treating intracranial hypertension, as it was associated with the most favorable cerebral hemodynamics and fastest resolution of intracranial hypertension. PMID- 26673841 TI - Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery. AB - OBJECTIVES: Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay. DESIGN: Single-center retrospective matched cohort study. SETTING: A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California. PATIENTS: Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91). CONCLUSIONS: The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings. PMID- 26673842 TI - Comparison of the New Adult Ventilator-Associated Event Criteria to the Centers for Disease Control and Prevention Pediatric Ventilator-Associated Pneumonia Definition (PNU2) in a Population of Pediatric Traumatic Brain Injury Patients. AB - OBJECTIVES: The new Centers for Disease Control and Prevention paradigm for ventilator-associated events is intended to simplify surveillance of infectious and noninfectious complications of mechanical ventilation in adults. We assessed the ventilator-associated events algorithm in pediatric patients. DESIGN: A retrospective observational cohort study. SETTING: This single-center study took place in a PICU at an urban academic medical facility. PATIENTS: Pediatric (ages 0-18 yr old) trauma patients with moderate-to-severe traumatic brain injury ventilated for greater than or equal to 2 days. MEASUREMENTS AND MAIN RESULTS: We assessed for pediatric ventilator-associated pneumonia (as defined by current Centers for Disease Control and Prevention PNU2 guidelines), adult ventilator associated events, and an experimental ventilator-associated events definition modified for pediatric patients. We compared ventilator-associated events to ventilator-associated pneumonia to calculate the test characteristics. Thirty nine of 119 patients (33%) developed ventilator-associated pneumonia. Sensitivity of the adult ventilator-associated condition definition was 23% (95% CI, 11-39%), which increased to 56% (95% CI, 40-72%) using the modified pediatric ventilator associated pneumonia criterion. Specificity reached 100% for both original and modified pediatric probable ventilator-associated pneumonia using ventilator associated events criteria. Children who developed ventilator-associated pneumonia or ventilator-associated condition had similar baseline characteristics: age, mechanism of injury, injury severity scores, and use of an intracranial pressure monitor. Diagnosis of ventilator-associated pneumonia and ventilator-associated condition portended similarly unfavorable outcomes: longer median duration of ventilation, ICU and hospital length of stay, and more discharges to rehabilitation, home health, or nursing care compared with patients with no pulmonary complication. CONCLUSIONS: Both current and modified ventilator associated events criteria have poor sensitivity but good specificity in identifying pediatric ventilator-associated pneumonia. Despite poor sensitivity, the high specificity of the ventilator-associated events diagnoses does provide a useful and objective metric for interinstitution ICU comparison. Ventilator associated pneumonia and ventilator-associated condition were both associated with excess morbidity in pediatric traumatic brain injury patients. PMID- 26673843 TI - Impact of Retrieval, Distance Traveled, and Referral Center on Outcomes in Unplanned Admissions to a National PICU. AB - OBJECTIVES: Centralization of PICUs requires a transport system that delivers patient outcomes equivalent to that of the same institution admissions. Our aim was to evaluate how pediatric critical care retrieval, distance traveled, and referral center level of ICU support impact on outcomes in unplanned admissions. DESIGN: Retrospective cohort study. SETTING: The national PICU in New Zealand. PATIENTS: A total of 5,609 (45% retrieved) unplanned pediatric admissions (< 15 yr) between January 1, 2004, and January 1, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data analyzed included case-mix, source of admission, diagnostic category, Pediatric Index of Mortality score, PICU-specific resource use, distance traveled, transport duration, and referral hospital ICU level. Outcome measures were crude and risk-adjusted PICU mortality and PICU length of stay. Compared with nontransported admissions, retrieved children were younger, more frequently admitted outside normal working hours, had higher predicted mortality (median Pediatric Index of Mortality score, 4.7% vs 1.5%; p < 0.001) and PICU-specific resource use (respiratory support, vasoactive infusions, and renal replacement therapy). The transport cohort had greater crude mortality rates (8.6% vs 5.6%; p < 0.008) and a median of 29 hours longer PICU stay. There was no significant difference in risk-adjusted mortality between the cohorts (observed/expected mortality ratio for retrieved patients, 0.84 vs nontransported patients, 0.91; p = 0.73). Neither distance traveled (median, 135 km), transport duration (median, 4.4 hr), nor the level of ICU at the referral center had a significant effect on risk-adjusted PICU mortality in the retrieved cohort. CONCLUSIONS: Children retrieved to the national PICU in New Zealand have greater predicted mortality risk and PICU-specific resource use than nontransported patients. There is no significant difference in risk-adjusted mortality between retrieved and the same institution admissions. Critically ill pediatric patients can be transported long distances by specially trained and equipped transport teams, without an increase in risk-adjusted PICU mortality. PMID- 26673844 TI - Pediatric Hematopoietic Stem Cell Transplant and Intensive Care: Have Things Changed? AB - OBJECTIVES: Mortality for pediatric patients who require intensive care posthematopoietic stem cell transplant still remains high. Previously at our institution, survival rates were 44% for patients who required mechanical ventilation posthematopoietic stem cell transplant. We conducted a review of patients to identify whether there has been any improvement in survival over the past 12 years and to identify any risk factors that contribute to mortality. DESIGN: Retrospective chart review. SETTING: PICU and hematopoietic stem cell transplant unit of a single tertiary children's hospital. PATIENTS: Children less than 18 years old undergoing hematopoietic stem cell transplant who required admission to the ICU between January 2000 and December 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 350 separate admissions to the ICU for 206 patients posthematopoietic stem cell transplant. Median Age was 9.3 years (range, 1-17 yr). Median time from hematopoietic stem cell transplant to admission was 35 days (interquartile range, 13-152 d), and 59% of patients were male. Survival to ICU discharge for all admissions was 75%, which equated to 57% of all patients. Of the admissions that required invasive mechanical ventilation, 48% survived to ICU discharge, with a survival to ICU discharge of 36% if there was more than one admission requiring mechanical ventilation. Survival to ICU discharge was 33% if renal replacement therapy was required. Mechanical ventilation, inotrope/vasopressor use, and number of organ dysfunction within an admission were predictors of mortality. Having an underlying malignant condition or an autologous hematopoietic stem cell transplant was associated with a more favorable outcome. CONCLUSIONS: This is the largest single-center series for pediatric patients who require intensive care posthematopoietic stem cell transplant and demonstrates that this group of patients still faces high mortality. There has been an improvement in survival for those patients who require renal replacement therapy and also for patients who require mechanical ventilation more than once; however, the need for mechanical ventilation still remains a significant predictor of mortality. PMID- 26673845 TI - Secondary traumatization and attachment among wives of former POWs: a longitudinal study. AB - The aim of the present study was to examine the directionality of the association between post-traumatic stress symptoms (PTSS) and attachment insecurities across time among indirect trauma survivors. Wives of former prisoners of war (ex-POWs), with and without post-traumatic stress disorder (PTSD), and comparable controls were assessed 30 (T1) and 38 (T2) years after the Yom Kippur War. As expected, wives of ex-POWs endorsed higher PTSS compared to wives of controls. Wives of ex POWs with PTSD endorsed higher PTSS and higher attachment avoidance compared to wives of ex-POWs without PTSD and controls. There were significant associations between PTSS and attachment insecurities. Contrary to the hypothesis, the relationship between PTSS and attachment insecurities among wives of ex-POWs was unidirectional, with attachment anxiety at T1 predicting PTSS at T2, and not vice versa. Results indicate that attachment anxiety might act as a risk factor for secondary traumatic reactions. PMID- 26673846 TI - Measurement of Small Molecular Dopant F4TCNQ and C60F36 Diffusion in Organic Bilayer Architectures. AB - The diffusion of molecules through and between organic layers is a serious stability concern in organic electronic devices. In this work, the temperature dependent diffusion of molecular dopants through small molecule hole transport layers is observed. Specifically we investigate bilayer stacks of small molecules used for hole transport (MeO-TPD) and p-type dopants (F4TCNQ and C60F36) used in hole injection layers for organic light emitting diodes and hole collection electrodes for organic photovoltaics. With the use of absorbance spectroscopy, photoluminescence spectroscopy, neutron reflectometry, and near-edge X-ray absorption fine structure spectroscopy, we are able to obtain a comprehensive picture of the diffusion of fluorinated small molecules through MeO-TPD layers. F4TCNQ spontaneously diffuses into the MeO-TPD material even at room temperature, while C60F36, a much bulkier molecule, is shown to have a substantially higher morphological stability. This study highlights that the differences in size/geometry and thermal properties of small molecular dopants can have a significant impact on their diffusion in organic device architectures. PMID- 26673847 TI - Beer, wine and lifestyle: a cross-sectional study of the Belgian military population. AB - BACKGROUND: A reduction in mortality associated with wine drinking compared to beer drinking has been suggested in the past. A recent meta-analysis could not confirm the observed differential effect. Other characteristics not related to specific components of beer and wine must play a role in the relationship between wine and mortality, thereby explaining the differential protective results. METHODS: A military population was selected to investigate the lifestyle differences between beer and wine drinkers. A food-frequency questionnaire was used to register alcohol and food consumption, together with questionnaires for health-related and lifestyle characteristics. Three dietary patterns were characterized by the Healthy Eating Index 2010, the Mediterranean Diet Score and a pattern obtained by principal component analysis. RESULTS: In the multivariate analysis, beer consumption decreased with increasing age, military rank, physical activity and dietary pattern scores. Beer consumption increased with total energy intake and with smoking. CONCLUSIONS: Wine consumption was associated with a healthier lifestyle compared with beer consumption. Those differences must be taken into account when relating types of alcoholic beverage consumption with health-related outcomes. PMID- 26673848 TI - RELATIONSHIP BETWEEN THE Y BALANCE TEST SCORES AND SOFT TISSUE INJURY INCIDENCE IN A SOCCER TEAM. AB - BACKGROUND: Although the dynamic balance has been proposed as a risk factor for sports-related injuries, few researchers have used the Y balance test to examine this relationship. The purpose of this study was to determine if the Y Balance Test (YBT) is a valid test for determining subjects susceptible to soft tissue injury among soccer players on a professional team. STUDY DESIGN: Prospective cohort. METHODS AND MEASURES: Prior to the 2011 football (soccer) season, the anterior, posteromedial and posterolateral YBT reach distances and limb lengths of 74 soccer players were measured. Athletes' physiotherapists documented how many days the players were unable to play due to the injuries. After normalizing for lower limb length, each of the reach distances, right/left reach distance difference and composite reach distance were examined using odds ratios and logistic regression analysis. RESULTS: Logistic regression models indicated that players with a difference of equal or greater than 4cm between lower limbs in posteromedial direction were 3.86 more likely to sustain a lower extremity injury (p=0.001). Results indicate that players who had lower scores than the mean in each reach direction, independently, were almost two times more likely to sustain an injury. CONCLUSIONS: The results suggest that YBT can be incorporated into physical examinations to identify soccer players who are susceptible to risk of injury. LEVEL OF EVIDENCE: 2b. PMID- 26673850 TI - Duplication of Right Testicular Vein: Embryological and Clinical Consideration- A Case Report. AB - The testis is the organ upon which the survival of the human species depends. Abnormalities of testicular vessels may lead to loss of gametogenesis and hormone production. The gonadal veins are anatomically asymmetric and there are several anatomical variations involving them. In present case, a variation in draining pattern of right gonadal vein was observed during a routine dissection done at Department of Anatomy. Duplication of right gonadal vein near the point of drainage was found. One of the veins was draining in inferior vena cava and other into right renal vein. According to the reviewed literature, a case like this was rarely reported. There was no other vascular abnormality in this case. Variation in gonadal veins remains unnoticed clinically, but these variations are incidental findings during autopsy and surgeries. The presence of such variations can increase risk of varicocoele and infertility in patients. PMID- 26673849 TI - Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan. AB - AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. METHODS: Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.11 0.43], older age (OR = 0.32, 95%CI: 0.16-0.66) and endoscopic atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries. PMID- 26673851 TI - Risk, risk reduction and management of occult malignancy diagnosed after uterine morcellation: a commentary. AB - Minimally invasive surgical techniques compared with laparotomy offer the advantages of less intraoperative blood loss, shorter hospitalization, fewer wound complications and faster return to baseline activity for both hysterectomy and myomectomy. While morcellation allows for the laparoscopic removal of large specimens, it may result in intraperitoneal dissemination of benign disease or upstaging of occult malignancy leading to compromised survival. There has been heightened scrutiny over appropriate patient selection and preoperative assessment in light of recent warnings against power morcellation issued by the US FDA. This commentary therefore summarizes the magnitude of such risks associated with uterine morcellation, current national regulatory statements and potential merits of risk-reducing approaches such as contained morcellation. The importance of patient counseling is underscored. PMID- 26673852 TI - A novel simple measure correlates to the outcome in 57 patients with intracerebellar hematomas. Results of a retrospective analysis. AB - BACKGROUND: The incidence of intracerebellar hemorrhages approaches 5-10% of all intracerebral hematomas. The clinical presentation varies from headaches and dizziness to rapid deterioration of consciousness to the point of coma in severe cases. In order to find some concrete criteria that could influence the prognosis of these patients, we performed this retrospective study. METHODS: We retrospectively analyzed the factors influencing the outcome of 57 patients with intracerebellar hematomas treated in our clinic in the last 7 years. The Glasgow Coma Scale (GCS) on admission, as well as other parameters as hypertension, diabetes mellitus, presence of malign tumors in the medical history, or the intake of anticoagulants were assessed as independent factors influencing the outcome of the patients. On the other hand, various computed tomography parameters on admission were also correlated with the clinical outcome such as, tight posterior fossa (TPF), volume of the hematoma, hydrocephalus, compression of the fourth ventricle, intraventricular bleeding, as well as the ratio of the maximal width of the hematoma in comparison to the width of the PF were taken into consideration. RESULTS: The results of the study showed that patients with poor GCS on admission had also a poor Glasgow Outcome Score. Interestingly there was a statistically significant correlation between the maximal width of the hematoma in comparison to the width of the PF and the outcome of the patients. It could be also shown that the patients with intraventricular hemorrhage, hydrocephalus, compression of the fourth ventricle over 50% of its maximal width and TPF, had a poor clinical outcome. Moreover, there was a statistically significant correlation of the volume of the hematoma and a poor clinical outcome. CONCLUSIONS: We introduced as a new factor that is, the cerebellar hemorrhage/PF ratio and found out that the value >35% was associated to an unfavorable outcome. PMID- 26673853 TI - Treatment of non-muscle invasive bladder cancer with Bacillus Calmette-Guerin (BCG): Biological markers and simulation studies. AB - Intravesical Bacillus Calmette-Guerin (BCG) vaccine is the preferred first line treatment for non-muscle invasive bladder carcinoma (NMIBC) in order to prevent recurrence and progression of cancer. There is ongoing need for the rational selection of i) BCG dose, ii) frequency of BCG administration along with iii) synergistic adjuvant therapy and iv) a reliable set of biochemical markers relevant to tumor response. In this review we evaluate cellular and molecular markers pertinent to the immunological response triggered by the BCG instillation and respective mathematical models of the treatment. Specific examples of markers include diverse immune cells, genetic polymorphisms, miRNAs, epigenetics, immunohistochemistry and molecular biology 'beacons' as exemplified by cell surface proteins, cytokines, signaling proteins and enzymes. We identified tumor associated macrophages (TAMs), human leukocyte antigen (HLA) class I, a combination of Ki-67/CK20, IL-2, IL-8 and IL-6/IL-10 ratio as the most promising markers for both pre-BCG and post-BCG treatment suitable for the simulation studies. The intricate and patient-specific nature of these data warrants the use of powerful multi-parametral mathematical methods in combination with molecular/cellular biology insight and clinical input. PMID- 26673855 TI - LC-UV-Guided Isolation and Structure Determination of Lancolide E: A Nortriterpenoid with a Tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-Bridged System from a "Talented" Schisandra Plant. AB - Lancolide E (1) featuring a complex tetracyclo[5.4.0.0(2,4).0(3,7)]undecane bridged system that is constructed by an eight-, a three-, and two five-membered carbon rings in a sterically congested region was obtained in trace amounts from a "talented" schinortriterpenoid producer Schisandra lancifolia. Its structure was fully characterized by combining 2D NMR spectroscopy, theoretical calculations, and X-ray diffraction analysis. The biogenetic pathway of 1 was proposed to involve a Prins cyclization. PMID- 26673854 TI - Pancreatic Metastases from Tumors in the Urogenital Tract. AB - BACKGROUND: Isolated pancreatic metastases or pancreatic metastases with limited extrapancreatic disease are uncommon and account for only 2-4% of resected malignant pancreatic lesions in surgical series. However, clear-cell renal cell carcinoma is the predominant primary tumor and accounts for more than 60% of cases with isolated pancreatic metastases. Pancreatectomy is the treatment of choice for most patients with isolated pancreatic metastases from renal cell cancer. SUMMARY: This review provides an overview of clinical presentation and diagnosis as well as surgical management, including patient selection for surgery and surgical technique for pancreatic metastases of renal cell carcinoma. KEY MESSAGE: Although there is no high-level evidence that surgical resection of pancreatic metastases improves survival, the survival results of several observational series and of systematic reviews are promising and support pancreatic resection as part of a multimodal treatment. The reported median survival and 5-year survival rates after pancreatic resection range from 6 to 10 years and from 55 to 75%, respectively. Pancreatic resection is effective for local control. However, extrapancreatic progression frequently occurs. With the introduction of novel systemic therapy options such as tyrosine kinase inhibitors, the prognosis of metastatic renal cell carcinoma has improved, and this will affect the role of pancreatic resection for metastases. PRACTICAL IMPLICATIONS: Pancreatic resection for isolated renal cell carcinoma is safe and effective, may confer a survival benefit and should, therefore, be considered in patients for whom no contraindication for surgery exists. PMID- 26673856 TI - Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy. AB - Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 degrees C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future. PMID- 26673857 TI - Comparative Evaluation of Propolis, Metronidazole with Chlorhexidine, Calcium Hydroxide and Curcuma Longa Extract as Intracanal Medicament Against E.faecalis- An Invitro Study. AB - INTRODUCTION: The increase of potential side effects and safety concerns of conventional medicaments have led to the recent popularity of herbal alternative medications. The herbal products are known for its high antimicrobial activity, biocompatibility, anti-inflammatory and antioxidant properties. AIM: The purpose of this study was to investigate and compare the effectiveness of Propolis, Metronidazole with Chlorhexidine gel, Curcuma Longa and Calcium Hydroxide for elimination of E.faecalis bacteria in extracted teeth samples. MATERIALS AND METHODS: Ninety extracted single rooted intact teeth were taken for the study. Decoronation, removal of apices and chemomechanical preparation was done for all samples. These sterilized samples were then contaminated with pure culture of E.faecalis under laminar flow. The samples were incubated for a period of 21 days. The infected samples were assigned to 5 groups: Group I- Propolis; Group II Metronidazole with Chlorhexidine gel; Group III- Calcium hydroxide; Group IV- Curcuma Longa; and control group- Saline. Efficacy of newer intracanal medicaments against E.faecalis were carried out in the samples at the end of 1, 2 & 5 days for each group with the help of colorimeter. Student paired t-test, ANOVA and multiple tukey test were used for statistical analysis. RESULTS: The value of optical density was statistically significant in all groups when compared to that of control group. Group I (Propolis) produced better antimicrobial efficacy followed by Chlorhexidine Metronidazole combination, Curcuma Longa and Calcium hydroxide. CONCLUSION: Within the limitations of this study, it can be concluded that Propolis showed better antimicrobial properties against E.faecalis than other medicaments. PMID- 26673858 TI - A Three Year Clinicopathological Study of Cases of Rupture Uterus. AB - INTRODUCTION: Rupture uterus is a life threatening obstetric complication with serious maternal and fetal side-effects. We report a 3 year (2010-2013) retrospective clinical study of pregnancy with rupture uterus cases attending a tertiary care hospital. AIM: The aim of the study was to evaluate the incidence of rupture uterus, incidence as per age, parity, clinical presentations, risk factors, complications and management. MATERIALS AND METHODS: Retrospective data of 74 cases of rupture uterus in SCB Medical college, Cuttack was collected from case records of 26,547 deliveries during a 3 year span (2010-2013). Parameters like cause of rupture, type, site of rupture and outcome were recorded. The collected data was analysed by SPSS software v19. RESULTS: Out of 26,547 deliveries during the three year period, there were 74 cases of rupture uterus with an incidence of rupture 1 in 359 (0.28%). The mean age of rupture uterus was 27.4 years. 95.8% were multigravida and majority were referred cases from low socioeconomic status. Only 40.5% had the required minimum of four antenatal visits as recommended by WHO (World Health Organisation). A total of 48.6% of cases with rupture uterus had history of previous Caesarean section. Prolonged labour was present in 75.6% of the cases. Only 12.2% of the cases had history of oxytocin use whereas 9.5% had undergone an operative vaginal delivery. Obstructed labour was the cause in 24.3% of cases, 85.1% had complete rupture. Majority had a rupture in the anterior wall (69%) and 81.1% had rupture in lower segment of uterus. Only 17.6% had broad ligament haematoma, 10.8% colporrhexis and 6.8% had associated bladder injury. Repair was possible in only 39.2% of cases, whereas majority landed up in hysterectomy. Internal iliac ligation was done in 2.7% of cases. Perinatal mortality was 90.5% whereas maternal death was seen in 13.5% cases. One patient developed VVF (vesicovaginal fistula). Duration of hospital stay was upto 14 days in 81.1% cases. CONCLUSION: Education and proper care especially of high risk patients like previous caesarean by competent personnal, proper use of oxytocin and early referral may help to reduce the incidence of "rupture uterus". PMID- 26673859 TI - Streptococcus pneumoniae as cause of infection in infants less than 60 days of age: serotypes and antimicrobial susceptibility. AB - OBJECTIVE: The aim of this study was to determine the distribution of serotypes and the antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates causing invasive and non-invasive disease in children aged <=60 days in hospitals in Mexico. METHODS: A 15-year retrospective study was conducted for the period 2000 to 2014. Pneumococcal clinical isolates were serotyped by Quellung reaction, and antimicrobial susceptibility testing was performed with the broth microdilution method. RESULTS: A total of 126 pneumococcal isolates were collected. Pneumonia was the most frequent diagnosis (40.5%), followed by meningitis (29.4%), septicemia (16.7%), and other clinical entities, including otitis media and conjunctivitis (13.5%). The most frequent serotypes before the introduction of heptavalent pneumococcal conjugate vaccine (PCV7) were 19F, 23F, 7F, and 35B. Serotypes 3, 6A, 10A, 12F, and 15A/B increased after the introduction of PCV7. Serotype 19A was isolated most frequently in the pneumonia and meningitis cases only after the introduction of PCV7, and it displayed a high resistance to penicillin. CONCLUSIONS: Although the number of infections in infants aged <=60 days was low, such infections were not unusual events. New vaccination strategies should be evaluated to limit the risks in this age group. PMID- 26673860 TI - Anterior Cruciate Ligament Reconstruction Using a Flexible Reamer System: Technique and Pitfalls. AB - Anatomic reconstruction of the anterior cruciate ligament (ACL) has been shown to improve stability of the knee, particularly rotational stability, potentially leading to superior clinical outcomes and a shorter return to sport. Nonanatomic ACL reconstruction has been linked to graft failure and abnormal cartilage loading thought to contribute to progression of degenerative joint disease. Use of the far anteromedial portal (FAMP) to uncouple the tibial and femoral tunnels has led to improved reproduction of the femoral footprint and facilitates drilling of the femoral tunnel in an anatomic position. The use of the FAMP and straight reamer systems introduces its own set of potential complications, including short femoral tunnels and peroneal nerve injury. These potential complications have been addressed by drilling the femoral tunnel in a hyperflexed position, which can lead to difficulty with positioning the operative extremity, visualization, and identification of anatomic landmarks. The purpose of this case report was to review the advantages and technical aspects of using a flexible reamer system and the FAMP to achieve an anatomic ACL reconstruction while avoiding potential complications and pitfalls. Flexible reamer systems allow an additional way of uncoupling the tibial and femoral tunnels to clearly visualize and establish an anatomic starting point within the femoral footprint of the native ACL while avoiding the complications associated with knee hyperflexion and straight reamers with the far anteromedial portal. In the authors' experience, an anatomic reconstruction of the ACL can be achieved safely using flexible reamers while avoiding some of the difficulties seen with straight reamers used in conjunction with an uncoupled, far anteromedial approach. PMID- 26673861 TI - Radiosynovectomy in rheumatic diseases. AB - Radiosynovectomy is a safe and repeatable treatment method of chronic synovitis with synovial overgrowth and refractory chronic or acute inflammatory joint effusion. It consist in the intraarticular administration of a radioactive isotope in the form of a colloid causing the extinguishing of active synovitis. The radiocolloid causes permanent irradiation of the synovium with beta ray electron beams, which ultimately leads to its fibrosis and extinguishes the inflammatory process destroying the joint. The main indications for radiosynovectomy include chronic and acute arthritis in the course of systemic diseases, intraarticular bleeding in hemorrhagic diatheses (hemophilia), selected cases of osteoarthritis, recurrent effusions following surgery, e.g. arthroplasty, or other iatrogenic post-surgery complications causing arthritis. Radiosynovectomy is also performed in pigmented villonodular synovitis and crystal synovitis. The most common method used to determine the eligibility for radiosynovectomy is an ultrasound, which shows the location and activity of the thickened synovium. The administration of a radiocolloid into the joint, sheath or bursa should also be performed under the control of the ultrasound image, as this ensures a precise location of the puncture needle and full control of the isotope administration process. Clinical efficacy of radiosynovectomy depends on the proper qualification of patients for the procedure. The success rate of radiosynovectomy in common indications is 65-80%. It is confirmed by the visualization of avascular (fibrotic) synovium in follow-up ultrasound tests. The aim of this article is to present techniques and indications for the radiosynovectomy treatment. PMID- 26673863 TI - Chloride capping of CdTiO3 for higher crystallinity and enhanced photocatalytic activity. AB - The crystallinity of cadmium titanate (CdTiO3) was greatly improved when synthesized under mild reaction conditions, in the presence of chloride. The highly crystalline CdTiO3 showed much enhanced photodegradation of methyl orange (MO) under simulated sunlight. CdTiO3 was characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption/desorption, photoluminescence (PL), and UV/vis spectrometry. The enhanced photodegradation was attributed to the better charge separation owing to its higher crystallinity. PMID- 26673862 TI - Histological and Clinicopathological Evaluation of Liver Allograft Biopsy: An Initial Experience of Fifty Six Biopsies. AB - INTRODUCTION: Liver biopsy is gold standard for diagnosis of allograft dysfunction. AIM: The aim of study was to evaluate liver allograft biopsies performed for graft dysfunction, study the pattern of injury and intensity, and timeline of occurrence of graft dysfunction. MATERIALS AND METHODS: Retrospective study was carried out of 56 liver allograft biopsies and their histological findings with clinical presentation were correlated. Totally 56 needle liver allograft biopsies from January 1210 to July 2014, obtained from 35 patients were studied for histological and clinicopathological evaluation. RESULTS: The mean age was 53.2+/-5.48 years. The most common original disease was alcoholic cirrhosis. The most common histological lesion was acute cellular rejection (ACR) in 31 (55.36%) biopsies followed by preservation-reperfusion injury (PRI) in 10 (17.86%) biopsies and drug toxicity in 8 (14.29%) biopsies. Chronic rejection was reported in 2 (3.57%) and recurrence of HCV in 3 (5.36%). Ischemic coagulative necrosis and acute cholangitis were seen in 1 (1.79 %) case each. CONCLUSION: Alcoholic cirrhosis was the most common etiology for end stage liver disease. ACR and PRI were the major complications in liver allograft biopsies at our centre. PMID- 26673864 TI - Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example of the median nerve. AB - Ultrasonography is an established method for imaging peripheral nerves. It serves to supplement the physical examination, electromyography, and magnetic resonance imaging. It enables the identification of post-traumatic changes of nerves, neuropathies secondary to compression syndromes, inflammatory or neoplastic nerve lesions as well as the evaluation of postoperative complications. In certain situations, this technique is the imaging method of choice. It is increasingly used in anesthesiology for regional anesthesia. As in the case of other ultrasound imaging studies, the examination of peripheral nerves is non-invasive, well-tolerated by patients, and relatively inexpensive. This article presents the histological structure of peripheral nerves and their appearance in ultrasonography. It also presents the examination technique, following the example of the median nerve, and includes a series of diagrams and ultrasound images. The interpretation of the shape, echogenicity, thickness and vascularity of nerves is described, as well as their relation to the surrounding tissues. The "elevator technique", which consists of locating a set nerve at a characteristic anatomic point, and following it proximally or distally, has been explained. The undisputed benefits of the ultrasound examination have been presented, including its advantages over other diagnostic methods. These advantages include the dynamic component of the ultrasound examination and the possibility of correlating the patient's symptoms with the ultrasound images. As an example, the proper anatomy and the ultrasonographic appearance of the median nerve were described. This nerve's course is presented, its divisions, and characteristic reference points, so as to facilitate its location and identification, and enable subsequent use of the aforementioned "elevator technique". This article opens a series of publications concerning anatomy, technique of examination and pathologies of peripheral nerves. PMID- 26673866 TI - From the incoming Editor in Chief. PMID- 26673865 TI - Protein aggregation, structural disorder and RNA-binding ability: a new approach for physico-chemical and gene ontology classification of multiple datasets. AB - BACKGROUND: Comparison between multiple protein datasets requires the choice of an appropriate reference system and a number of variables to describe their differences. Here we introduce an innovative approach to discriminate multiple protein datasets (multiCM) and to measure enrichments in gene ontology terms (cleverGO) using semantic similarities. RESULTS: We illustrate the powerfulness of our approach by investigating the links between RNA-binding ability and other protein features, such as structural disorder and aggregation, in S. cerevisiae, C. elegans, M. musculus and H. sapiens. Our results are in striking agreement with available experimental evidence and unravel features that are key to understand the mechanisms regulating cellular homeostasis. CONCLUSIONS: In an intuitive way, multiCM and cleverGO provide accurate classifications of physico chemical features and annotations of biological processes, molecular functions and cellular components, which is extremely useful for the discovery and characterization of new trends in protein datasets. The multiCM and cleverGO can be freely accessed on the Web at http://www.tartaglialab.com/cs_multi/submission and http://www.tartaglialab.com/GO_analyser/universal . Each of the pages contains links to the corresponding documentation and tutorial. PMID- 26673868 TI - NHC-based pincer ligands: carbenes with a bite. AB - In this frontier article we overview the emergence and scope of NHC-based CCC and CNC pincer systems, i.e. complexes containing mer-tridentate ligands bearing two NHC donor groups, comment on their effectiveness in applications, and highlight areas for future development and exploitation. PMID- 26673867 TI - Activin-betaC modulates cachexia by repressing the ubiquitin-proteasome and autophagic degradation pathways. AB - BACKGROUND: Cancer-associated cachexia and muscle wasting are considered key determinants of cancer-related death and reduction in the quality of life of cancer patients. A crucial link has been established between activin signaling and skeletal muscle atrophy-hypertrophy. We previously showed that activin-betaC, a novel activin-A antagonist, is a tumor modulator that abolishes the cancer associated cachexia in a mouse genetic model of gonadal tumorigenesis, in which the normal balance of inhibin/activin signalling is disrupted by a targeted mutation in the Inha gene (inhibin alpha-KO mouse). This study aimed to identify the molecular mechanism by which activin-betaC increases survival and abolishes cancer-associated cachexia in alpha-KO mice. We hypothesized that overexpression of activin-betaC modulates the cachexia phenotype by antagonizing the activin signaling pathway and repressing muscle wasting via the ubiquitin-proteasome and the autophagic-lysosomal degradation pathways. METHODS: Male and female ActC++, alpha-KO, and alpha-KO/ActC++ mice and WT littermate controls were studied. Western blot analysis for the specific E3 ubiquitin ligases, atrogin-1 and MuRF1, markers of the autophagic-lysosomal pathway, Beclin-1, p62, and LC3A/B, effectors Smad-2, Smad-3 and myostatin was performed in the gastrocnemius of age-matched mice. Histopathology of the gastrocnemius and survival analysis were also conducted in animals from the same breeding cohort. Serum levels of activin-A, inflammatory cytokines, hormonal profile, and bone density were also assessed. RESULTS: Increased levels of atrogin-1, MuRF-1, Beclin-1, p62, LC3A/B-I, Smad-2 and serum levels of activin-A were noted in the alpha-KO mice. These mice developed gonadal cancers followed by severe weight loss, and reduced survival. Overexpression of activin- betaC antagonized the activin signaling cascade, attenuating the ubiquitin-proteasome and the autophagic-lysosomal degradation pathways, and reduced serum levels of activin-A. alpha-KO/ActC++ mice displayed a less aggressive cachectic phenotype, reduced tumor weight, and prolonged survival. CONCLUSION: Our findings show for the first time a specific effect of activin-betaC on muscle wasting and transcription factors involved in muscle protein degradation. The study indicates that activin-betaC may be a novel therapy to abrogate cancer-associated weight loss and prolong survival. PMID- 26673869 TI - Glucocorticoids in tuatara (Sphenodon punctatus): Some influential factors, and applications in conservation management. AB - Glucocorticoid (GC) hormones promote basic life processes, regulate life-history transitions, and help individuals cope with challenges and stressors, thereby playing an important fitness role. Here, we review recent evidence for several factors that influence plasma concentrations of corticosterone (CORT), the main GC in tuatara (Sphenodon punctatus), and discuss the application of CORT as a physiological tool to monitor conservation efforts. Observational studies show an association between CORT concentrations and seasonal reproductive activity, ambient temperature, and ecological habitat parameters (including presence of rats/seabird abundance, sex-ratio, and genetic diversity), and experimental studies show a positive influence of acute temperature increase on the CORT response. Recently, CORT physiology has been applied as a monitoring tool in tuatara translocation programmes. No signs of chronic stress in CORT profiles were observed during standard short- and long-term translocation and rat eradication procedures, giving confidence that current conservation efforts are supportive in population recovery. These results provide a foundation for comparative understanding of stress physiology in reptiles, and will be critical for managing future population viability of tuatara in a changing environment. PMID- 26673870 TI - Effect of weather conditions and presence of visitors on adrenocortical activity in captive African penguins (Spheniscus demersus). AB - A number of potential stressors are present in captive environments and it is critically important to identify them in order to improve health and welfare in ex situ animal populations. In this study, we investigated the adrenocortical activity of a colony of African penguins hosted in an immersive zoo in Italy, with respect to the presence of visitors and local microclimatic conditions, using the non-invasive method of assessing faecal glucocorticoid metabolites (FGMs). The penguins' exhibit is a large naturalistic outdoor enclosure, which closely reproduces the natural habitat of this species. Data collection took place from the beginning of June to the end of August 2014, during the period of maximum flow of visitors. We carried out 12 sampling periods, each involving 2 consecutive days; during the first day we counted the visitors and we registered the meteorological data, and on the second day, we collected the faecal samples, which amounted to a total of 285 faecal samples. Our results showed that the number of visitors did not influence the adrenocortical activity of the African penguins. Conversely, the local microclimatic conditions did influence the physiological stress on these birds. We found that an increase of the daily mean temperature induced a significant increase in FGM concentrations, although humidity and wind speed had a moderating effect on temperature and reduced the heat-induced stress. Moreover, we calculated two climatic indices, commonly used to assess the thermal discomfort in animals, namely the THI (Temperature-Humidity Index) and WCI (Wind Chill Index), and we detected a positive relationship between their values and the FGM levels, demonstrating that these indices could be useful indicators of weather discomfort in African penguins. Our study shows that the simulating naturalistic conditions could have significant benefits for zoo animals, such as reducing the negative effect of visitors. Nevertheless, it should be taken into account where the zoological facility is located and if the local microclimatic conditions are compatible with the hosted species, to ensure that they do not differ greatly from their natural habitat. PMID- 26673871 TI - Non-invasive monitoring of stress hormones in the bat Eptesicus isabellinus - Do fecal glucocorticoid metabolite concentrations correlate with survival? AB - Chronic stress may negatively impact fitness and survival in wildlife. Stress hormone analysis from feces is a non-invasive tool for identifying stressors and deducing about individual and population level fitness. Although many bat populations are endangered, fecal stress hormone analysis has not been established in bats as a method for focusing conservation efforts. The isabelline serotine bat, Eptesicus isabellinus, is exposed to human disturbance as its roosts are mostly found in anthropogenic structures. Moreover, this bat is host to various diseases and survival rates between colonies may vary significantly. To validate the analysis of fecal glucocorticoid metabolites, we applied an adrenocorticotropic hormone (ACTH) challenge and tested four different enzyme immunoassays (EIA) for measuring glucocorticoid concentrations. Cortisol and its metabolites showed the highest increase in blood and feces after the ACTH challenge, but corticosterone and its metabolites also increased significantly. Baseline fecal cortisol metabolite (FCM) concentrations did not increase until 1.5h after the animals were captured, which is a convenient time lag for sample collection from captured animals. We furthermore compared baseline FCM concentrations between five colonies of E. isabellinus in Andalusia, Spain, and tested for their correlation with survival rates. FCM concentrations did not vary between colonies, but FCM levels increased with the animals' age. FCM analysis may prove a useful tool for identifying bat colonies that experience uncommon environmental stress. However, inter-individual variation in hormone secretion, due to factors such as age, may require additional information to properly interpret differences in hormone concentrations. PMID- 26673872 TI - Hormonal regulation of platypus Beta-lactoglobulin and monotreme lactation protein genes. AB - Endocrine regulation of milk protein gene expression in marsupials and eutherians is well studied. However, the evolution of this complex regulation that began with monotremes is unknown. Monotremes represent the oldest lineage of extant mammals and the endocrine regulation of lactation in these mammals has not been investigated. Here we characterised the proximal promoter and hormonal regulation of two platypus milk protein genes, Beta-lactoglobulin (BLG), a whey protein and monotreme lactation protein (MLP), a monotreme specific milk protein, using in vitro reporter assays and a bovine mammary epithelial cell line (BME-UV1). Insulin and dexamethasone alone provided partial induction of MLP, while the combination of insulin, dexamethasone and prolactin was required for maximal induction. Partial induction of BLG was achieved by insulin, dexamethasone and prolactin alone, with maximal induction using all three hormones. Platypus MLP and BLG core promoter regions comprised transcription factor binding sites (e.g. STAT5, NF-1 and C/EBPalpha) that were conserved in marsupial and eutherian lineages that regulate caseins and whey protein gene expression. Our analysis suggests that insulin, dexamethasone and/or prolactin alone can regulate the platypus MLP and BLG gene expression, unlike those of therian lineage. The induction of platypus milk protein genes by lactogenic hormones suggests they originated before the divergence of marsupial and eutherians. PMID- 26673873 TI - Estimation of Sex From Index and Ring Finger Lengths in An Indigenous Population of Eastern India. AB - INTRODUCTION: Forensic anthropology involves the identification of human remains for medico-legal purposes. Estimation of sex is an essential element of medico legal investigations when identification of unknown dismembered remains is involved. AIM: The present study was conducted with an aim to estimate sex from index and ring finger lengths of adult individuals belonging to an indigenous population of eastern India. MATERIALS AND METHODS: A total of 500 unrelated adult individuals (18-60 years) from the Rajbanshi population (males: 250, females: 250) took part in the study. A total of 400 (males: 200, 200 female) participants were randomly used to develop sex estimation models using Binary Logistic Regression Analysis (BLR). A separate group of 200 adults (18-60 years) from the Karbi tribal population (males 100, females 100) were included to validate the results obtained on the Rajbanshi population. The univarate and bivariate models derived on the study group (n=400) were tested on hold-out sample of Rajbanshi participants (n=100) and the other test population of the Karbi (n=200) participants. RESULTS: The results indicate that Index Finger Length (IFL) and Ring Finger Length (RFL) of both hands were significantly longer in males as compared to females. The ring finger was longer than the index finger in both sexes. The study successfully highlights the existence of sex differences in IFL and RFL (p<0.05). No sex differences were however, observed for the index and ring finger ratio. The predictive accuracy of IFL and RFL in sex estimation ranged between 70%-75% (in the hold out sample from the Rajbanshi population) and 60-66% (in the test sample from the Karbi population). A Receiver Operating Curve (ROC) analysis was performed to test the predictive accuracy after predicting the probability of IFL and RFL in sex estimation. The predicted probabilities using ROC analysis were observed to be higher on the left side and in multivariate analysis. CONCLUSION: The study concludes that sex estimation from index and ring finger lengths could be of utility when more reliable means of sex estimation are not available during medico-legal investigations. PMID- 26673875 TI - Solid Pseudopapillary Tumor in a Pregnant Woman: Imaging Findings and Literature Review. AB - A solid pseudopapillary neoplasm is a rare pancreatic tumor accounting for 1-2% of exocrine pancreatic neoplasms. It is usually asymptomatic and discovered incidentally. It is mainly seen in young women between the second and third decades of life. Although it usually has a large size at the time of diagnosis, it is considered to have low malignant potential. Solid pseudopapillary tumors (SPTs) have characteristic magnetic resonance imaging (MRI) features that enable it to be differentiated from other more common pancreatic tumors. Here, we report the case of a 34-year-old pregnant woman who was admitted to The Royal Hospital, Oman, with a large mass in her pancreas, which was incidentally discovered during abdominal ultrasonography. The mass was investigated further with MRI. The MRI revealed a well-defined mass related to the tail and body of the pancreas with solid and cystic components. It had a heterogeneous texture with fluid levels of different signal intensities due to the presence of blood of different ages. The cystic-solid appearance of an encapsulated lesion with characteristic signal intensity on MRI suggested the possibility of a SPT. Postoperative histopathology results confirmed the diagnosis of a SPT. In this case report, we highlight the MRI features of a SPT and discuss how to differentiate it from other cystic pancreatic tumors to increase the awareness of clinicians to this rare pancreatic tumor. PMID- 26673874 TI - Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer risk: results from a prospective study of women with a sister with breast cancer. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit several pathways in experimental models of breast carcinogenesis, but epidemiological evidence remains insufficient to support their use for breast cancer prevention. We examined the association between use of NSAIDs and breast cancer risk in a prospective cohort. METHODS: The Sister Study is a prospective cohort study of women who had a sister(s) with breast cancer. As of December 2013, 2118 incident breast cancers were ascertained from 50,884 women enrolled between 2003 and 2009. Lifetime history of NSAID use was estimated from self reported data in pill-years, with 1 pill per week for a year equivalent to 1 pill year. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer in relation to pill-years of use for different NSAIDs, with adjustment for potential confounders. RESULTS: In the full cohort, although there was some evidence that use of non-aspirin, non-COXib NSAIDs was associated with lower breast cancer risk, there was little evidence of overall association for most categories of NSAID use. Among postmenopausal women NSAID use was not associated with reduced risk of breast cancer. However, among premenopausal women there was significantly reduced risk for any NSAID (HR4vs1=0.66, 95% CI: 0.50-0.87) and specifically for aspirin (HR4vs1=0.57, 95% CI: 0.33-0.98), with small, but non significant reductions in risk for other drug classes. CONCLUSION: Women with a sister with breast cancer are themselves at increased risk and might benefit the most from chemoprevention. Although there was little evidence of protective effect from NSAIDs in the overall cohort of women or among the subset who are postmenopausal, there is intriguing evidence that NSAID use, particularly aspirin, may reduce risk among premenopausal women. PMID- 26673876 TI - Molecular Characterization of Five Potyviruses Infecting Korean Sweet Potatoes Based on Analyses of Complete Genome Sequences. AB - Sweet potatoes (Ipomea batatas L.) are grown extensively, in tropical and temperate regions, and are important food crops worldwide. In Korea, potyviruses, including Sweet potato feathery mottle virus (SPFMV), Sweet potato virus C (SPVC), Sweet potato virus G (SPVG), Sweet potato virus 2 (SPV2), and Sweet potato latent virus (SPLV), have been detected in sweet potato fields at a high (~95%) incidence. In the present work, complete genome sequences of 18 isolates, representing the five potyviruses mentioned above, were compared with previously reported genome sequences. The complete genomes consisted of 10,081 to 10,830 nucleotides, excluding the poly-A tails. Their genomic organizations were typical of the Potyvirus genus, including one target open reading frame coding for a putative polyprotein. Based on phylogenetic analyses and sequence comparisons, the Korean SPFMV isolates belonged to the strains RC and O with >98% nucleotide sequence identity. Korean SPVC isolates had 99% identity to the Japanese isolate SPVC-Bungo and 70% identity to the SPFMV isolates. The Korean SPVG isolates showed 99% identity to the three previously reported SPVG isolates. Korean SPV2 isolates had 97% identity to the SPV2 GWB-2 isolate from the USA. Korean SPLV isolates had a relatively low (88%) nucleotide sequence identity with the Taiwanese SPLV-TW isolates, and they were phylogenetically distantly related to SPFMV isolates. Recombination analysis revealed that possible recombination events occurred in the P1, HC-Pro and NIa-NIb regions of SPFMV and SPLV isolates and these regions were identified as hotspots for recombination in the sweet potato potyviruses. PMID- 26673877 TI - Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica. AB - BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-beta treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood. METHODS: OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber. RESULTS: Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin alphavbeta3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways. CONCLUSION: These results indicate that osteopontin is involved in NMO pathology. GENERAL SIGNIFICANCE: Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO. PMID- 26673878 TI - Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice. AB - India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice. PMID- 26673879 TI - Successful intrauterine treatment and good long-term outcome in an extremely severe case of fetal hemolytic disease. AB - A 34-year-old multiparous woman presented with anti-Rh-D antibodies (1: 512) and fetal hydrops at the 21(st) week of gestation. Ultrasound revealed massive fetal skin edema, ascites, hepatomegaly, placentomegaly, and anhydramnios. No fetal movements were observed. Fetal heart was enlarged, with reportedly decreased contractibility. The Doppler parameters were abnormal: the peak systolic velocity in median cerebral artery (MCA PSV) was increased (84 cm/s, 3 MoM), and absent end diastolic flow (AEDF) was reported in the umbilical artery. Ultrasound examination indicated severe fetal anemia and heart failure. Umbilical vein puncture was performed and the fetal blood count was determined (RBC 0.01 * 10(6)/ul, Ht 0.1%, PLT 67 * 10(3)/ul, WBC 2.1 * 10(3)/ul, indeterminable hemoglobin level). Packed red blood cells (0 Rh-, 30 ml) were immediately transfused to the fetus. Altogether, seven intrauterine transfusions were performed. Fetal hydrops disappeared gradually during the next few weeks. The male neonate (1860 g, 45 cm, Apgar score 3-4) was delivered after the last transfusion at 34(th) week of gestation due of intrauterine asphyxia. The infant was discharged after 21 days, in good condition, on breastfeeding. There was one 10 mm focus of periventricular leukomalacia in the brain, diagnosed based on trans-fontanel ultrasound, without any signs of damage to other organs. At the age of 5 years, the child is healthy, with no abnormalities in his neurodevelopmental parameters. PMID- 26673880 TI - Investigating combination HIV prevention: isolated interventions or complex system. AB - INTRODUCTION: Treatment as prevention has mobilized new opportunities in preventing HIV transmission and has led to bold new UNAIDS targets in testing, treatment coverage and transmission reduction. These will require not only an increase in investment but also a deeper understanding of the dynamics of combining behavioural, biomedical and structural HIV prevention interventions. High-income countries are making substantial investments in combination HIV prevention, but is this investment leading to a deeper understanding of how to combine interventions? The combining of interventions involves complexity, with many strategies interacting with non-linear and multiplying rather than additive effects. DISCUSSION: Drawing on a recent scoping study of the published research evidence in HIV prevention in high-income countries, this paper argues that there is a gap between the evidence currently available and the evidence needed to guide the achieving of these bold targets. The emphasis of HIV prevention intervention research continues to look at one intervention at a time in isolation from its interactions with other interventions, the community and the socio-political context of their implementation. To understand and evaluate the role of a combination of interventions, we need to understand not only what works, but in what circumstances, what role the parts need to play in their relationship with each other, when the combination needs to adapt and identify emergent effects of any resulting synergies. There is little development of evidence-based indicators on how interventions in combination should achieve that strategic advantage and synergy. This commentary discusses the implications of this ongoing situation for future research and the required investment in partnership. We suggest that systems science approaches, which are being increasingly applied in other areas of public health, could provide an expanded vocabulary and analytic tools for understanding these complex interactions, relationships and emergent effects. CONCLUSIONS: Relying on the current linear but disconnected approaches to intervention research and evidence we will miss the potential to achieve and understand system-level synergies. Given the challenges in sustaining public health and HIV prevention investment, meeting the bold UNAIDS targets that have been set is likely to be dependent on achieving systems level synergies. PMID- 26673882 TI - Modelling effects of public health educational campaigns on drinking dynamics. AB - This paper deals with the global property of a drinking model with public health educational campaigns. With the help of Lyapunov function, global stability of equilibria of the model is derived. The alcohol-free equilibrium is globally asymptotically stable and the alcohol problems are eliminated from population if [Formula: see text]. A unique alcohol present equilibrium is globally asymptotically stable if [Formula: see text]. Furthermore, the basic reproductive [Formula: see text] for the model is compared with the basic reproductive number [Formula: see text] for the absence of public health educational campaigns. We conclude that the public health educational campaigns of drinking individuals can slow down the drinking dynamics. Some numerical simulations are also given to explain our conclusions. PMID- 26673881 TI - Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition? AB - The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM IV diagnosis of "autism". The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger's Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence. PMID- 26673883 TI - Development of a smart guide wire using an electrostrictive polymer: option for steerable orientation and force feedback. AB - The development of steerable guide wire or catheter designs has been strongly limited by the lack of enabling actuator technologies. This paper presents the properties of an electrostrive actuator technology for steerable actuation. By carefully tailoring material properties and the actuator design, which can be integrated in devices, this technology should realistically make it possible to obtain a steerable guide wire design with considerable latitude. Electromechanical characteristics are described, and their impact on a steerable design is discussed. PMID- 26673884 TI - Performances and mechanistic investigations of a triphosphine trioxide/ionic liquid system for rare earth extraction. AB - The extraction of rare earth elements (REEs) from nitric acid solution with a triphosphine trioxide (TPO) is presented. Performances of such a ligand in ionic liquids vs. a classical solvent (benzyl ether) are compared. TPO seems to be 10 to 100 times more efficient when it is dissolved in ionic media whatever the concentration of nitric acid involved. Mechanistic investigations reveal that cation exchange classically observed in ionic liquids is not consistent with the experimental data. Moreover, clear differences in the TPO/Ln complexes between classical and ionic media are highlighted. A stable complex of 1 lanthanide for 3 TPO is formed in an ionic liquid whereas a complex of 1 lanthanide for 6 to 9 TPO is formed in benzyl ether. Back extraction is also studied and good recovery of REEs could be obtained. The TPO/ionic liquid system shows remarkable performances i.e. efficiency and selectivity towards lanthanides in a simulated leaching solution of a Nd/Fe/B/Dy magnet. PMID- 26673885 TI - Genome-Wide Analysis of Seed Acid Detergent Lignin (ADL) and Hull Content in Rapeseed (Brassica napus L.). AB - A stable yellow-seeded variety is the breeding goal for obtaining the ideal rapeseed (Brassica napus L.) plant, and the amount of acid detergent lignin (ADL) in the seeds and the hull content (HC) are often used as yellow-seeded rapeseed screening indices. In this study, a genome-wide association analysis of 520 accessions was performed using the Q + K model with a total of 31,839 single nucleotide polymorphism (SNP) sites. As a result, three significant associations on the B. napus chromosomes A05, A09, and C05 were detected for seed ADL content. The peak SNPs were within 9.27, 14.22, and 20.86 kb of the key genes BnaA.PAL4, BnaA.CAD2/BnaA.CAD3, and BnaC.CCR1, respectively. Further analyses were performed on the major locus of A05, which was also detected in the seed HC examination. A comparison of our genome-wide association study (GWAS) results and previous linkage mappings revealed a common chromosomal region on A09, which indicates that GWAS can be used as a powerful complementary strategy for dissecting complex traits in B. napus. Genomic selection (GS) utilizing the significant SNP markers based on the GWAS results exhibited increased predictive ability, indicating that the predictive ability of a given model can be substantially improved by using GWAS and GS. PMID- 26673886 TI - Involvement of nucleotide diphosphate kinase 2 in the reopening of the sensitive period of filial imprinting of domestic chicks (Gallus gallus domesticus). AB - Filial imprinting is a behavior characterized by the sensitive or critical period restricted to the first few days after hatching. Once the sensitive period is closed, it is widely believed that chicks can never be imprinted under natural conditions. Previously, we showed that the exogenous injection of T3 reopened the sensitive period which was already closed. That study suggested that T3 functioned by way of a rapid non-genomic action; however, the molecular mechanism of how T3 reopens the sensitive period remains unknown. Here, we show that the phosphorylation level of nucleotide diphosphate kinase 2 (NDPK2) was upregulated following T3 injection. Pharmacological deprivation of the kinase activity of NDPK hampered the molecular process prerequisite for the reopening of the sensitive period of filial imprinting. Moreover, it is shown that the kinase activity of NDPK2 participates in the priming process by T3 signaling which endows the potential for learning. Our data indicate that NDPK2 plays a crucial role downstream of T3 action and that its phosphorylation is involved in the non genomic signaling during imprinting. PMID- 26673887 TI - Characteristics of corticospinal projections to the intrinsic hand muscles in skilled harpists. AB - The process of learning to play a musical instrument necessarily alters the functional organisation of the cortical motor areas that are involved in generating the required movements. In the case of the harp, the demands placed on the motor system are quite specific. During performance, all digits with the sole exception of the little finger are used to pluck the strings. With a view to elucidating the impact of having acquired this highly specialised musical skill on the characteristics of corticospinal projections to the intrinsic hand muscles, focal transcranial magnetic stimulation (TMS) was used to elicit motor evoked potentials (MEPs) in three muscles (of the left hand): abductor pollicis brevis (APB); first dorsal interosseous (FDI); and abductor digiti minimi (ADM) in seven harpists. Seven non-musicians served as controls. With respect to the FDI muscle-which moves the index finger, the harpists exhibited reliably larger MEP amplitudes than those in the control group. In contrast, MEPs evoked in the ADM muscle-which activates the little finger, were smaller in the harpists than in the non-musicians. The locations on the scalp over which magnetic stimulation elicited discriminable responses in ADM also differed between the harpists and the non-musicians. This specific pattern of variation in the excitability of corticospinal projections to these intrinsic hand muscles exhibited by harpists is in accordance with the idiosyncratic functional demands that are imposed in playing this instrument. PMID- 26673888 TI - Sagittal Abdominal Diameter to Measure Visceral Adipose Tissue in Overweight or Obese Adolescent Children and Its Role as A Marker of Insulin Resistance. AB - BACKGROUND: Measurement of sagittal abdominal diameter using a revalidated caliper is simple, inexpensive, non-invasive method. It strongly correlates with insulin resistance and can be used as a surrogate marker to predict risk for Type II Diabetes Mellitus. AIM: To assess visceral abdominal fat by measuring sagittal abdominal diameter using sliding calipers and to predict insulin resistance in obese or overweight adolescent children. STUDY DESIGN: Explorative study for Paediatric age group among over weight and obese children aged 10-18 years in urban population in a Tertiary Care Centre. MATERIALS AND METHODS: Paediatric population satisfying ADA guidelines for diagnosis of prediabetes were included in the study. Anthropometric measurements with SAD were recorded. Blood was collected to investigate for prediabetes and insulin resistance using HOMA-IR. RESULTS: Out of 924 subjects who gave assent to participate in study 108 fulfilled ADA criteria. 33 subjects who didn't come for the follow up were excluded. Out of 75 subjects 12 were detected to have insulin resistance (16%) and 63 were normal (84%). Pearson's partial correlation of HOMA-IR and OGTT with SAD has demonstrated it to be better correlation with Insulin Resistance (IR) than other anthropometric measurements. Fasting Glucose correlated better with Waist Hip Circumference. CONCLUSION: Insulin Resistance was diagnosed in 16% of the population and these had high levels of insulin resistance. SAD in relation to glucose metabolism, had a better correlation with OGTT followed by HOMA-IR and fasting Insulin. SAD with anthropometric measurements had better correlation all the parameters other than Waist Circumference, which had negative correlation. SAD can be used in evaluation of obese or overweight children for evaluation. PMID- 26673889 TI - Evaluation of phenotypic and molecular methods for identification of Streptococcus pneumoniae. AB - AIM: The objective of this study is to compare various Streptococcus pneumoniae identification methods. MATERIALS & METHODS: In total, 1371 putative S. pneumoniae isolates were tested with three phenotypic methods and a molecular based method targeting a virulence factor (CpsA). We assessed the sensitivity and the specificity of each method and widely used S. pneumoniae identification algorithm. RESULTS: None of the methods or the identification algorithm used separately was able to correctly identify all S. pneumoniae isolates. Furthermore, a high rate of optochin resistance was found. CONCLUSIONS: We demonstrated the failure of the current S. pneumoniae identification methods and optochin susceptibility-based algorithm. In addition, the high rate of optochin resistance might justify the necessity of a close monitoring of optochin susceptibility. PMID- 26673890 TI - The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin. AB - Uromodulin is the most abundant protein in the urine. It is exclusively produced by renal epithelial cells and it plays key roles in kidney function and disease. Uromodulin mainly exerts its function as an extracellular matrix whose assembly depends on a conserved, specific proteolytic cleavage leading to conformational activation of a Zona Pellucida (ZP) polymerisation domain. Through a comprehensive approach, including extensive characterisation of uromodulin processing in cellular models and in specific knock-out mice, we demonstrate that the membrane-bound serine protease hepsin is the enzyme responsible for the physiological cleavage of uromodulin. Our findings define a key aspect of uromodulin biology and identify the first in vivo substrate of hepsin. The identification of hepsin as the first protease involved in the release of a ZP domain protein is likely relevant for other members of this protein family, including several extracellular proteins, as egg coat proteins and inner ear tectorins. PMID- 26673891 TI - Specialized areas for value updating and goal selection in the primate orbitofrontal cortex. AB - The macaque orbitofrontal cortex (OFC) is essential for selecting goals based on current, updated values of expected reward outcomes. As monkeys consume a given type of reward to satiety, its value diminishes, and OFC damage impairs the ability to shift goal choices away from devalued outcomes. To examine the contributions of OFC's components to goal selection, we reversibly inactivated either its anterior (area 11) or posterior (area 13) parts. We found that neurons in area 13 must be active during the selective satiation procedure to enable the updating of outcome valuations. After this updating has occurred, however, area 13 is not needed to select goals based on this knowledge. In contrast, neurons in area 11 do not need to be active during the value-updating process. Instead, inactivation of this area during choices causes an impairment. These findings demonstrate selective and complementary specializations within the OFC. PMID- 26673892 TI - Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes. AB - Previously, we reported that ATXN1 oligomers are the primary drivers of toxicity in Spinocerebellar ataxia type 1 (SCA1; Lasagna-Reeves et al., 2015). Here we report that polyQ ATXN1 oligomers can propagate locally in vivo in mice predisposed to SCA1 following intracerebral oligomeric tissue inoculation. Our data also show that targeting these oligomers with passive immunotherapy leads to some improvement in motor coordination in SCA1 mice and to a modest increase in their life span. These findings provide evidence that oligomer propagation is regionally limited in SCA1 and that immunotherapy targeting extracellular oligomers can mildly modify disease phenotypes. PMID- 26673893 TI - A versatile pipeline for the multi-scale digital reconstruction and quantitative analysis of 3D tissue architecture. AB - A prerequisite for the systems biology analysis of tissues is an accurate digital three-dimensional reconstruction of tissue structure based on images of markers covering multiple scales. Here, we designed a flexible pipeline for the multi scale reconstruction and quantitative morphological analysis of tissue architecture from microscopy images. Our pipeline includes newly developed algorithms that address specific challenges of thick dense tissue reconstruction. Our implementation allows for a flexible workflow, scalable to high-throughput analysis and applicable to various mammalian tissues. We applied it to the analysis of liver tissue and extracted quantitative parameters of sinusoids, bile canaliculi and cell shapes, recognizing different liver cell types with high accuracy. Using our platform, we uncovered an unexpected zonation pattern of hepatocytes with different size, nuclei and DNA content, thus revealing new features of liver tissue organization. The pipeline also proved effective to analyse lung and kidney tissue, demonstrating its generality and robustness. PMID- 26673894 TI - AMPylation matches BiP activity to client protein load in the endoplasmic reticulum. AB - The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP affects protein folding homeostasis and the response to ER stress. Reversible inactivating covalent modification of BiP is believed to contribute to the balance between chaperones and unfolded ER proteins, but the nature of this modification has so far been hinted at indirectly. We report that deletion of FICD, a gene encoding an ER-localized AMPylating enzyme, abolished detectable modification of endogenous BiP enhancing ER buffering of unfolded protein stress in mammalian cells, whilst deregulated FICD activity had the opposite effect. In vitro, FICD AMPylated BiP to completion on a single residue, Thr(518). AMPylation increased, in a strictly FICD-dependent manner, as the flux of proteins entering the ER was attenuated in vivo. In vitro, Thr(518) AMPylation enhanced peptide dissociation from BiP 6-fold and abolished stimulation of ATP hydrolysis by J-domain cofactor. These findings expose the molecular basis for covalent inactivation of BiP. PMID- 26673896 TI - Sources of noise during accumulation of evidence in unrestrained and voluntarily head-restrained rats. AB - Decision-making behavior is often characterized by substantial variability, but its source remains unclear. We developed a visual accumulation of evidence task designed to quantify sources of noise and to be performed during voluntary head restraint, enabling cellular resolution imaging in future studies. Rats accumulated discrete numbers of flashes presented to the left and right visual hemifields and indicated the side that had the greater number of flashes. Using a signal-detection theory-based model, we found that the standard deviation in their internal estimate of flash number scaled linearly with the number of flashes. This indicates a major source of noise that, surprisingly, is not consistent with the widely used 'drift-diffusion modeling' (DDM) approach but is instead closely related to proposed models of numerical cognition and counting. We speculate that this form of noise could be important in accumulation of evidence tasks generally. PMID- 26673895 TI - A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. AB - CRM1 is a highly conserved, RanGTPase-driven exportin that carries proteins and RNPs from the nucleus to the cytoplasm. We now explored the cargo-spectrum of CRM1 in depth and identified surprisingly large numbers, namely >700 export substrates from the yeast S. cerevisiae, ~1000 from Xenopus oocytes and >1050 from human cells. In addition, we quantified the partitioning of ~5000 unique proteins between nucleus and cytoplasm of Xenopus oocytes. The data suggest new CRM1 functions in spatial control of vesicle coat-assembly, centrosomes, autophagy, peroxisome biogenesis, cytoskeleton, ribosome maturation, translation, mRNA degradation, and more generally in precluding a potentially detrimental action of cytoplasmic pathways within the nuclear interior. There are also numerous new instances where CRM1 appears to act in regulatory circuits. Altogether, our dataset allows unprecedented insights into the nucleocytoplasmic organisation of eukaryotic cells, into the contributions of an exceedingly promiscuous exportin and it provides a new basis for NES prediction. PMID- 26673897 TI - A case report of lameness in two dairy goat herds; a suspected combination of nutritional factors concurrent with treponeme infection. AB - BACKGROUND: Two dairy goat farms with high level of lameness in lactating animals were presented for further investigation. Farm 1 and Farm 2 presented with 37 and 67% morbidity, respectively. Both farms had an all year round indoor system, feeding ad libitum concentrate with forage available at all times. CASE PRESENTATION: The lameness was found to be based in the foot. Previous treatments consisting of biweekly footbathing with zinc sulphate, spraying lesions with oxytetracycline spray and packing lesions with copper crystals on a single occasion and single injections with long acting oxytetracycline had not been successful. Mild cases had signs of haemorrhaging in the white line or on the sole of the foot. Moderate cases showed under running of the wall horn or small areas of exposed sole corium. Severe cases would consist of horn or wall separation with the corium exposed and infected. In extreme cases only the wall horn of the claw remained, with a large area of necrotic tissue in the centre and no healthy corium visible. Only one animal was seen to have interdigital lesions. Polymerase chain reaction (PCR) and culture of swabs taken from exposed corium and the interdigital space were negative for Dichelobacter nodosus but PCR for treponemes were positive in both the adults and the youngstock tested. Due to the high level of concentrate in the diet of these goats, nutrition was thought to contribute to the problem. Transcutaneous rumen fluid samples were taken and pH was measured on both farms, with 35% of the samples below pH value 5.5. CONCLUSION: No definite diagnosis could be made. However, the results suggest both treponemes and nutrition play a role in the aetiology of the lameness. The initial sole or wall horn lesions were thought to be secondarily infected by treponemes. Further investigation is needed to definitively diagnose the cause and contributing factors for this lameness. PMID- 26673899 TI - Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis. AB - The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (alpha-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of alpha-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing alpha-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing alpha-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver alpha-MSH for DSS-induced ulcerative colitis therapy. PMID- 26673898 TI - Economic Analysis of Immunization Strategies for PRRS Control [corrected]. AB - Porcine reproductive and respiratory syndrome virus (PRRSv) is a swine-specific pathogen that causes significant increases in production costs. When a breeding herd becomes infected, in an attempt to hasten control and elimination of PRRSv, some veterinarians have adopted a strategy called load-close-expose which consists of interrupting replacement pig introductions into the herd for several weeks (herd closure) and exposing the whole herd to a replicating PRRSv to boost herd immunity. Either modified-live virus (MLV) vaccine or live field-virus inoculation (FVI) is used. This study consisted of partial budget analyses to compare MLV to FVI as the exposure method of load-close-expose program to control and eliminate PRRSv from infected breeding herds, and secondly to estimate benefit / cost of vaccinating sow herds preventatively. Under the assumptions used in this study, MLV held economic advantage over FVI. However, sensitivity analysis revealed that decreasing margin over variable costs below $ 47.32, or increasing PRRSv-attributed cost above $18.89 or achieving time-to-stability before 25 weeks resulted in advantage of FVI over MLV. Preventive vaccination of sow herds was beneficial when the frequency of PRRSv infection was at least every 1 year and 9 months [corrected]. The economics of preventative vaccination was minimally affected by cost attributed to field-type PRRSv infection on growing pigs or by the breeding herd productivity level. The models developed and described in this paper provide valuable tools to assist veterinarians in their efforts to control PRRSv. PMID- 26673900 TI - Incorporation of O(6)-methylguanine restricts the conformational conversion of the human telomere G-quadruplex under molecular crowding conditions. AB - Here we systematically studied the incorporation of O(6)-methylguanine (6mG) into different positions of the human telomere G-quadruplex. In contrast to the natural G-quadruplex, the 6mG incorporated G-quadruplexes impeded the conformational conversion of the G-quadruplex from a hybrid to a parallel structure under molecular crowding conditions in a K(+) containing buffer. PMID- 26673901 TI - A Theoretical Study on Stepwise- and Concertedness of the Mechanism of 1,3 Dipolar Cycloaddition Reaction Between Tetra Amino Ethylene and Trifluoro Methyl Azide. AB - The order of reaction, especially in 1,3-dipolar cycloadditions directly affects the products' stereo selectivity. Due to this fact that a wide range of heterocyclic rings of natural products and biologically active molecules are synthesizing via this valuable procedure, understanding about the order of this reaction is so useful in designing the synthesis of different types of heterocyclic species. Therefore, the order of 1, 3-dipolar reaction has been carefully studied by many researchers but it seems that this question is still open despite many valuable answers. Considering this, in the present work, it is attempted to pursue this subject by theoretical investigation of any possible pathway of 1, 3-dipolar reaction of tetra amino ethylene as a highly electron rich dipolarophile and trifluoro methyl azide as an electron poor 1,3-dipole. During the calculations, one, two, and three step mechanism(s) have been found to be possible for the present 1, 3-dipolar reaction. PMID- 26673903 TI - Highly Efficient Computation of the Basal kon using Direct Simulation of Protein Protein Association with Flexible Molecular Models. AB - An essential baseline for determining the extent to which electrostatic interactions enhance the kinetics of protein-protein association is the "basal" kon, which is the rate constant for association in the absence of electrostatic interactions. However, since such association events are beyond the milliseconds time scale, it has not been practical to compute the basal kon by directly simulating the association with flexible models. Here, we computed the basal kon for barnase and barstar, two of the most rapidly associating proteins, using highly efficient, flexible molecular simulations. These simulations involved (a) pseudoatomic protein models that reproduce the molecular shapes, electrostatic, and diffusion properties of all-atom models, and (b) application of the weighted ensemble path sampling strategy, which enhanced the efficiency of generating association events by >130-fold. We also examined the extent to which the computed basal kon is affected by inclusion of intermolecular hydrodynamic interactions in the simulations. PMID- 26673902 TI - Lower CSF Abeta is Associated with HAND in HIV-Infected Adults with a Family History of Dementia. AB - BACKGROUND: Both family history of dementia (FHD) and lower levels of Abeta-42 are indepentently associated with worse neurocognitive functioning in HIVinfected patients. OBJECTIVE: To examine the relationships between cerebrospinal fluid (CSF) Abeta-42 and FHD with HIV-associated neurocognitive disorders (HAND). METHODS: One hundred eighty-three HIV+ adults underwent neuropsychological and neuromedical assessments, and determination of CSF Abeta-42 concentration and FHD (defined as a self-reported first or second-degree relative with a dementia diagnosis). Univariate analyses and multivariable logistic regressions were used. RESULTS: FHD was not associated with HAND (p = 0.24); however, CSF Abeta-42 levels were lower (p = 0.03) in the HAND group, but were not associated with FHD (p = 0.89). Multivariable models showed a main effect of CSF Abeta-42 (p = 0.03) and a trend-level (p = 0.06) interaction between FHD and CSF Abeta-42, such that lower CSF Abeta-42 was associated with HAND in those with FHD (p < 0.01) compared to those without FHD (p = 0.83). An analysis in those with follow-up data showed that higher baseline CSF Abeta-42 was associated with lower risk of neurocognitive decline (p = 0.02). While we did not find an FHD X CSF Abeta-42 interaction (p = 0.83), when analyses were stratified by FHD, lower CSF Abeta-42 was associated at the trend-level with neurocognitive decline in the FHD group (p = 0.08) compared to the no FHD group (p = 0.15). CONCLUSION: FHD moderates the relationship between of CSF Abeta-42 and HAND. The findings highlight the complexities in interpreting the relationships between biomarkers of age-related neurodegeneration and HAND. PMID- 26673904 TI - Anatomic and physiopathologic changes affecting the airway of the elderly patient: implications for geriatric-focused airway management. AB - There are many anatomical, physiopathological, and cognitive changes that occur in the elderly that affect different components of airway management: intubation, ventilation, oxygenation, and risk of aspiration. Anatomical changes occur in different areas of the airway from the oral cavity to the larynx. Common changes to the airway include tooth decay, oropharyngeal tumors, and significant decreases in neck range of motion. These changes may make intubation challenging by making it difficult to visualize the vocal cords and/or place the endotracheal tube. Also, some of these changes, including but not limited to, atrophy of the muscles around the lips and an edentulous mouth, affect bag mask ventilation due to a difficult face-mask seal. Physiopathologic changes may impact airway management as well. Common pulmonary issues in the elderly (eg, obstructive sleep apnea and COPD) increase the risk of an oxygen desaturation event, while gastrointestinal issues (eg, achalasia and gastroesophageal reflux disease) increase the risk of aspiration. Finally, cognitive changes (eg, dementia) not often seen as related to airway management may affect patient cooperation, especially if an awake intubation is required. Overall, degradation of the airway along with other physiopathologic and cognitive changes makes the elderly population more prone to complications related to airway management. When deciding which airway devices and techniques to use for intubation, the clinician should also consider the difficulty associated with ventilating the patient, the patient's risk of oxygen desaturation, and/or aspiration. For patients who may be difficult to bag mask ventilate or who have a risk of aspiration, a specialized supralaryngeal device may be preferable over bag mask for ventilation. Patients with tumors or decreased neck range of motion may require a device with more finesse and maneuverability, such as a flexible fiberoptic broncho-scope. Overall, geriatric-focused airway management is necessary to decrease complications in this patient population. PMID- 26673906 TI - Widespread Bat White-Nose Syndrome Fungus, Northeastern China. PMID- 26673905 TI - Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal. AB - We present a two-photon microendoscope capable of in vivo label-free deep-tissue high-resolution fast imaging through a very long optical fiber. First, an advanced light-pulse spectro-temporal shaping device optimally precompensates for linear and nonlinear distortions occurring during propagation within the endoscopic fiber. This enables the delivery of sub-40-fs duration infrared excitation pulses at the output of 5 meters of fiber. Second, the endoscopic fiber is a custom-made double-clad polarization-maintaining photonic crystal fiber specifically designed to optimize the imaging resolution and the intrinsic luminescence backward collection. Third, a miniaturized fiber-scanner of 2.2 mm outer diameter allows simultaneous second harmonic generation (SHG) and two photon excited autofluorescence (TPEF) imaging at 8 frames per second. This microendoscope's transverse and axial resolutions amount respectively to 0.8 MUm and 12 MUm, with a field-of-view as large as 450 MUm. This microendoscope's unprecedented capabilities are validated during label-free imaging, ex vivo on various fixed human tissue samples, and in vivo on an anesthetized mouse kidney demonstrating an imaging penetration depth greater than 300 MUm below the surface of the organ. The results reported in this manuscript confirm that nonlinear microendoscopy can become a valuable clinical tool for real-time in situ assessment of pathological states. PMID- 26673907 TI - PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians. AB - BACKGROUND: Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. METHODS: A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. RESULTS: Of 114 patients, 66.7% showed elevated serum anti-PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. CONCLUSION: To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy. PMID- 26673908 TI - Dialysis modality choice in elderly patients with end-stage renal disease: a narrative review of the available evidence. AB - The number of elderly patients on maintenance dialysis has rapidly increased in the past few decades, particularly in developed countries, imposing a growing burden on dialysis centres. Hence, many nephrologists and healthcare authorities feel that greater emphasis should be placed on the promotion of home dialysis therapies such as peritoneal dialysis (PD) and home haemodialysis (HD). There is currently no general consensus as to the best dialysis modality for elderly patients with end-stage renal disease. In-centre HD is predominant in most countries, although it is widely recognized that PD has several advantages over HD, including the lack of need for vascular access, continuous slow ultrafiltration, less interference with patients' lifestyle and lower costs. Comparisons of outcomes between elderly patients on PD and HD rely on observational studies, as randomized controlled trials are lacking. The results of these studies are variable. However, most of them suggest that survival rates are largely similar between the two modalities, except for elderly patients with diabetes and/or beyond 1-3 years from dialysis initiation, in which cases HD appears to be superior. An equally important aspect to consider when choosing dialysis modality, particularly in this age group, is the quality of life, and in this regard most studies found no significant differences between PD and HD. In these circumstances, we believe that dialysis modality selection should be guided by patient's preference, based on comprehensive and unbiased information. A multidisciplinary team should review elderly patients starting on dialysis, aiming to identify possible barriers to PD and home HD, including physical, visual, cognitive, psychological and social problems, and to overcome such barriers by adequate care, education, psychological counselling and dialysis assistance. PMID- 26673909 TI - Increased phosphatidylserine-exposing microparticles and their originating cells are associated with the coagulation process in patients with IgA nephropathy. AB - BACKGROUND: Relatively little information is available about phosphatidylserine positive (PS(+)) microparticles (MPs) and their originating cells in IgA nephropathy (IgAN) despite well-established intraglomerular coagulation. Our objectives were to detect PS exposure on MP membranes and MP-origin cells and to evaluate its role in procoagulant activity (PCA) and fibrin formation and their association with pathological lesions in the disease. METHODS: Patients with IgAN and healthy controls were studied. Lactadherin was used to quantify PS exposure on MPs and MP-origin cells. PCA of MPs and MP-origin cells was evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure, fibrin strands and FVa/Xa binding were observed on MPs/cells using confocal microscopy. RESULTS: Using flow cytometry, we found that IgAN patients had high levels of PS(+) MPs derived from lymphocytes, monocytes, neutrophils, platelets, erythrocytes and endothelial cells (ECs). The PS exposure on MP-origin cells also increased in these patients. MPs and MP-origin cells (leukocytes, platelets and erythrocytes) isolated from IgAN patients and ECs cultured with IgAN serum had a significantly shorter median coagulation time (P < 0.001), higher median intrinsic FXa (P < 0.001) and higher thrombin (P < 0.001) generation than controls. These coagulation functional assays were associated with the glomerular lesions. The lesions were also correlated with glomerular fibrin deposition (all P < 0.05). In the presence of patient MPs or their related cells, fibrin formation peaked faster with a higher maximum turbidity when compared with healthy controls. Blocking PS with lactadherin in the IgAN group prolonged coagulation time to control levels, inhibited the PCA up to 80% and markedly reduced fibrin formation. More importantly, we observed that fibrin strands formed on MPs and ECs in the same regions that bound lactadherin, similar to the FVa/Xa costaining. CONCLUSIONS: We find that high levels of PS(+) MPs and the MP-origin cells are associated with the coagulation process in IgAN, and this may provide a previously unrecognized contribution to intraglomerular coagulation. PMID- 26673910 TI - Association of neuropsychiatric syndromes with global clinical deterioration in Alzheimer's disease patients. AB - BACKGROUND: Data on the relationship between behavioral disturbances in Alzheimer's disease (AD) and global clinical deterioration is still controversial. The purpose of this study was to explore potential correlations of neuropsychiatric syndromes with global clinical deterioration in patients with AD, with particular consideration on severity levels of dementia. METHODS: AD patients (n = 156) aged 76.7 years from Brazilian clinical centers were assessed to diagnose the five neuropsychiatric syndromes measured by the Neuropsychiatric Inventory-Clinician rating scale (NPI-C): psychosis, agitation, affective, apathy, and sleep. These syndromes were then analyzed for their correlation with the Global Deterioration Scale (GDS). To analyze the association of neuropsychiatric syndromes with the GDS, considering the total sample and patients grouped by dementia severity levels, we applied the coefficient of multiple correlation (Ryy), adjusted multiple linear regression, and the coefficient of determination (R2yx). We tested the significance of correlation coefficients using the Student t-test for simple correlations (a single independent variable) and analysis of variance (ANOVA) for multiple correlations. ANOVA was also used to compare means of demographic and some clinical variables at different levels of dementia. RESULTS: For the total sample, apathy and agitation syndromes were most strongly correlated (0.74; 0.72, respectively) with clinical deterioration according to the GDS, followed by psychosis (0.59), affective (0.45), and sleep syndromes (0.34). Agitation significantly correlated with mild and moderate dementia (CDR 1: 0.45; and CDR 2: 0.69, respectively). At CDR 2, agitation and affective syndromes were most strongly correlated (0.69; 0.59, respectively) with clinical deterioration while at CDR 3, the apathy syndrome was most strongly correlated with clinical deterioration (0.52). CONCLUSIONS: Agitation, apathy, and affective disorders were the syndromes most strongly correlated with global deterioration in AD patients, becoming more evident at severe stages of dementia. PMID- 26673911 TI - Correction: Predicting Early Mortality in Adult Trauma Patients Admitted to Three Public University Hospitals in Urban India: A Prospective Multicentre Cohort Study. PMID- 26673912 TI - A Scoping Literature Review: The State of Knowledge on Home Care Equipment and Supplies. AB - We explored the state of knowledge on home care supplies and equipment because not much is known about this topic. We used a scoping review for the literature review because it was the most appropriate approach considering the state of the literature. We searched for articles published in both the gray and peer-reviewed literature. We established five overarching themes based on the findings. These were supply management, durable medical equipment, wound care, best practices, and costs. This review demonstrates that although knowledge about home care supplies and equipment is growing, it is still an understudied area. PMID- 26673913 TI - Social Role Theory and Social Role Valorization for Care Management Practice. AB - This article proposes that social role theory (SRT) and social role valorization (SRV) be established as organizing theories for care managers. SRT is a recognized sociological theory that has a distinctive place in care management practice. SRV is an adjunct for SRT that focuses on people who are devalued by being in a negative social position and supports behavior change and movement to a valued social position. PMID- 26673914 TI - Recovering From the Suicide of a Client With Schizophrenia: Recommendations for Case Managers. AB - Many case managers in mental health settings occasionally experience a client's suicide, and this can be an emotionally devastating event. The symptoms of schizophrenia, including the difficulties those client face in forming trusting relationships with others, brings special challenges to the case manager's recovery because of the efforts put into developing that relationship. The purposes of this article are to describe a range of possible reactions of case managers following the suicide of a client with schizophrenia and how those persons can be helped to make a positive recovery from such an event. A summary of suicide risk factors for case managers to assess when working with clients who have schizophrenia is included. PMID- 26673915 TI - The Home-Delivered Meals Program: A Promising Intervention for Suburban Older Adults Living Alone. AB - This study examined differences in perceived benefits of home-delivered meals between older adults living alone and those living with others. Recommendations were also discussed to enhance services by examining differences between these two subgroups. This study used secondary data analysis focusing on two open-ended questions that were collected in a client satisfaction survey conducted by AgeOptions, the Area Agency on Aging (AAA) in suburban Cook County, Illinois. Out of 199 older adults or their caregivers who participated in the survey, 126 (63.3%) older adults were living alone. All of the survey participants shared their perception of home-delivered meals benefits, and 91 respondents (45.7%) offered recommendations on the program. The results suggest that there is a greater need for transportation options, financial security, regular safety checks, and basic support for older adults who live alone compared to those living with others. The most frequent recommendation from all older adults was increasing the variety of meal options. Older adults living alone complained less about taste and the way meals were cooked than older adults living with others, but they requested availability of meals customized for those with unique needs. Additionally, older adults living alone offered a wider range of recommendations for the program as well as identify more diverse benefits from the program than those living with others. PMID- 26673916 TI - A Public Health Nursing Model Assists Women Receiving Temporary Assistance for Needy Families Benefits to Identify a Usual Source of Primary Care. AB - Women enrolled in Florida's Temporary Assistance for Needy Families (TANF) program experience high rates of chronic health problems and often lack a usual source of care. Thus, in this study, we aimed to identify variables related to being in a usual source of care at time of study enrollment and determine whether a public health nursing case management intervention affected the obtainment of a usual source of care. To achieve these aims, we conducted a secondary analysis of a randomized controlled trial of a public health nursing case management intervention, which included women with chronic health conditions enrolled in TANF (n = 432). Results indicated 35% of the women did not identify a usual source of care at time of study enrollment, and the public health nursing intervention was effective in helping women obtain a usual source of care (OR = 2.5, 95% CI 1.004-6.491). Thus, a public health nursing case management intervention is an effective way to connect TANF participants to a usual source of care, which may lead to improved health outcomes in this vulnerable population of women. PMID- 26673917 TI - Incidence of new-onset wheeze: a prospective study in a large middle-aged general population. AB - BACKGROUND: Wheeze is a very common respiratory symptom, which is associated with several factors and diseases. Studies on incidence of new-onset wheeze in general adult populations are rare. The present prospective study aimed to investigate the incidence rate of new-onset wheeze, and predictors for wheeze, in a general, middle-aged population. METHODS: Individuals, born 1943-1973, who had participated in a previous Swedish study in 1993 (n = 15,813), were mailed a new respiratory questionnaire in 2003. The questionnaire, which included items about respiratory symptoms, atopy, and smoking was answered by 11,463 (72%). Incidence rates of new-onset wheeze were calculated. Cox regression analyses were performed with incident wheeze as an event and person-years under observation as dependent variable. RESULTS: Among those free of wheeze at baseline (n = 8885), there were 378 new cases of wheeze during the study period (1993-2003). The incidence rate was 4.3/1000 person-years. The adjusted risk was increased in relation to smoking (HR 2.1;95% CI 1.7-2.7), ex-smoking (HR 1.4;95% CI 1.1-1.9), young age (HR 1.7;95% CI 1.3-2.2), chronic bronchitis (HR 2.3;95% CI 0.96-5.7), and rhinitis (HR 1.8;95% CI 1.4-2.2) at baseline, and body mass index >=30 (HR 1.9;95% CI 1.5 2.6) at follow-up. CONCLUSIONS: This is a unique study that presents an incidence rate for new-onset wheeze in a middle-aged, general population sample previously free of adult wheeze. The results indicate that new-onset wheeze is quite common in this age group. Health care staff should bear this in mind since new-onset wheeze could be one of the earliest symptoms of severe respiratory disease. Special attention should be paid to patients with a smoking history, chronic bronchitis, rhinitis or obesity. PMID- 26673918 TI - Intra-abdominal fat. Part I. The images of the adipose tissue localized beyond organs. AB - Unaltered fat is a permanent component of the abdominal cavity, even in slim individuals. Visceral adiposity is one of the important factors contributing to diabetes, cardiovascular diseases and certain neoplasms. Moreover, the adipose tissue is an important endocrine and immune organ of complex function both when normal and pathological. Its role in plastic surgery, reconstruction and transplantology is a separate issue. The adipose tissue has recently drawn the attention of research institutes owing to being a rich source of stem cells. This review, however, does not include these issues. The identification of fat is relatively easy using computed tomography and magnetic resonance imaging. It can be more difficult in an ultrasound examination for several reasons. The aim of this paper is to present various problems associated with US imaging of unaltered intra-abdominal fat located beyond organs. Based on the literature and experience, it has been demonstrated that the adipose tissue in the abdominal cavity has variable echogenicity, which primarily depends on the amount of extracellular fluid and the number of connective tissue septa, i.e. elements that potentiate the number of areas that reflect and scatter ultrasonic waves. The normal adipose tissue presents itself on a broad gray scale: from a hyperechoic area, through numerous structures of lower reflection intensity, to nearly anechoic regions mimicking the presence of pathological fluid collections. The features that facilitate proper identification of this tissue are: sharp margins, homogeneous structure, high compressibility under transducer pressure, no signs of infiltration of the surrounding structures and no signs of vascularization when examined with the color and power Doppler. The accumulation of fat tissue in the abdominal cavity can be generalized, regional or focal. The identification of the adipose tissue in the abdominal cavity using ultrasonography is not always easy. When in doubt, the diagnostic process should be extended to include computed tomography or magnetic resonance imaging, or sometimes biopsy (preferably the core-needle one). PMID- 26673919 TI - Interactive Cognitive-Motor Step Training Improves Cognitive Risk Factors of Falling in Older Adults - A Randomized Controlled Trial. AB - PURPOSE: Interactive cognitive-motor training (ICMT) requires individuals to perform both gross motor movements and complex information processing. This study investigated the effectiveness of ICMT on cognitive functions associated with falls in older adults. METHODS: A single-blinded randomized controlled trial was conducted in community-dwelling older adults (N = 90, mean age 81.5+/-7) without major cognitive impairment. Participants in the intervention group (IG) played four stepping games that required them to divide attention, inhibit irrelevant stimuli, switch between tasks, rotate objects and make rapid decisions. The recommended minimum dose was three 20-minute sessions per week over a period of 16 weeks unsupervised at home. Participants in the control group (CG) received an evidence-based brochure on fall prevention. Measures of processing speed, attention/executive function (EF), visuo-spatial ability, concerns about falling and depression were assessed before and after the intervention. RESULTS: Eighty one participants (90%) attended re-assessment. There were no improvements with respect to the Stroop Stepping Test (primary outcome) in the intervention group. Compared to the CG, the IG improved significantly in measures of processing speed, visuo-spatial ability and concern about falling. Significant interactions were observed for measures of EF and divided attention, indicating group differences varied for different levels of the covariate with larger improvements in IG participants with poorer baseline performance. The interaction for depression showed no change for the IG but an increase in the CG for those with low depressive symptoms at baseline. Additionally, low and high-adherer groups differed in their baseline performance and responded differently to the intervention. Compared to high adherers, low adherers improved more in processing speed and visual scanning while high-adherers improved more in tasks related to EF. CONCLUSIONS: This study shows that unsupervised stepping ICMT led to improvements in specific cognitive functions associated with falls in older people. Low adherers improved in less complex functions while high-adherers improved in EF. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000671763. PMID- 26673920 TI - Hybrid de novo genome assembly of the Chinese herbal plant danshen (Salvia miltiorrhiza Bunge). AB - BACKGROUND: Danshen (Salvia miltiorrhiza Bunge), also known as Chinese red sage, is a member of Lamiaceae family. It is valued in traditional Chinese medicine, primarily for the treatment of cardiovascular and cerebrovascular diseases. Because of its pharmacological potential, ongoing research aims to identify novel bioactive compounds in danshen, and their biosynthetic pathways. To date, only expressed sequence tag (EST) and RNA-seq data for this herbal plant are available to the public. We therefore propose that the construction of a reference genome for danshen will help elucidate the biosynthetic pathways of important secondary metabolites, thereby advancing the investigation of novel drugs from this plant. FINDINGS: We assembled the highly heterozygous danshen genome with the help of 395 * raw read coverage using Illumina technologies and about 10 * raw read coverage by using single molecular sequencing technology. The final draft genome is approximately 641 Mb, with a contig N50 size of 82.8 kb and a scaffold N50 size of 1.2 Mb. Further analyses predicted 34,598 protein-coding genes and 1,644 unique gene families in the danshen genome. CONCLUSIONS: The draft danshen genome will provide a valuable resource for the investigation of novel bioactive compounds in this Chinese herb. PMID- 26673921 TI - SPAK and OSR1 Sensitive Kir2.1 K+ Channels. AB - BACKGROUND/AIMS: Kir2.1 (KCNJ2) channels are expressed in neurons, skeletal muscle and cardiac tissue and maintain the resting membrane potential. The activity of those channels is regulated by diverse signalling molecules. The present study explored whether Kir2.1 channels are sensitive to the transporter and channels regulating kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are in turn regulated by WNK (with-no-K[Lys]) kinases. METHODS: cRNA encoding Kir2.1 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild type SPAK, constitutively active T233E SPAK, WNK insensitive T233A SPAK, catalytically inactive D212A SPAK, wild-type OSR1, constitutively active T185E OSR1, WNK insensitive T185A OSR1 and catalytically inactive D164A OSR1. Inwardly rectifying K+ channel activity was quantified utilizing dual electrode voltage clamp and Kir2.1 channel protein abundance in the cell membrane was measured utilizing chemiluminescence of Kir2.1 containing an extracellular HA-tag epitope. RESULTS: Kir2.1 activity was significantly enhanced by wild-type SPAK and T233E SPAK, but not by T233A SPAK and D212A SPAK, as well as by wild-type OSR1 and T185E OSR1, but not by T185A OSR1 and D164A OSR1. As shown for SPAK, the kinases enhanced Kir2.1 protein abundance in the cell membrane. The difference of current and conductance between oocytes expressing Kir2.1 together with SPAK or OSR1 and oocytes expressing Kir2.1 alone was dissipated following a 24 hours inhibition of channel insertion into the cell membrane by brefeldin A (5 uM). CONCLUSIONS: SPAK and OSR1 are both stimulators of Kir2.1 activity. They are presumably effective by enhancing channel insertion into the cell membrane. PMID- 26673922 TI - Sulindac sulfide inhibits colon cancer cell growth and downregulates specificity protein transcription factors. AB - BACKGROUND: Specificity protein (Sp) transcription factors play pivotal roles in maintaining the phenotypes of many cancers. We hypothesized that the antineoplastic effects of sulindac and its metabolites were due, in part, to targeting downregulation of Sp transcription factors. METHODS: The functional effects of sulindac, sulindac sulfone and sulindac sulfide on colon cancer cell proliferation were determined by cell counting. Effects of these compounds on expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes were determined by western blot analysis of whole cell lysates and in transient transfection assays using GC-rich constructs. RESULTS: Sulindac and its metabolites inhibited RKO and SW480 colon cancer cell growth and the order of growth inhibitory potency was sulindac sulfide>>sulindac sulfone>sulindac. Treatment of SW480 and RKO cells with sulindac sulfide downregulated expression of Sp1, Sp3 and Sp4 proteins. Sulindac sulfide also decreased expression of several Sp-regulated genes that are critical for cancer cell survival, proliferation and angiogenesis and these include survivin, bcl-2, epidermal growth factor receptor (EGFR), cyclin D1, p65 subunit of NFkappaB and vascular endothelial growth factor (VEGF). Sulindac sulfide also induced reactive oxygen species (ROS) and decreased the level of microRNA-27a in colon cancer cells, which resulted in the upregulation of the Sp repressor ZBTB10 and this resulted in downregulation of Sp proteins. CONCLUSIONS: The results suggest that the cancer chemotherapeutic effects of sulindac in colon cancer cells are due, in part, to its metabolite sulindac sulfide which downregulates Sp transcription factors and Sp-regulated pro-oncogenic gene products. PMID- 26673924 TI - Usability of ultrasound assessment of gastric content. Case reports. AB - The paper presents the use of ultrasound assessment of gastric content in anesthesiological practice. Factors influencing pulmonary aspiration of gastric content and the risk of a complication in the form of aspiration pneumonia are discussed. The examination was performed on two patients hospitalized in a state of emergency who required surgical intervention. The first patient, a 46-year-old male with a phlegmon of the foot, treated for type 2 diabetes, ischemic heart disease and renal insufficiency, required urgent incision of the phlegmon. The second patient, a 36-year-old male with a post-traumatic pericerebral hematoma, qualified for an urgent trepanation. Interviews with the patients and their medical documentation indicated that they had been fasting for the recommended six hours before the surgery. However, during a gastric ultrasound examination it was found that food was still present in the stomach, which caused a change in the anesthesiological procedure chosen. The authors present a method of performing gastric ultrasound examination, determining the nature of the food content present and estimating its volume. PMID- 26673923 TI - TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice. AB - Prior findings in vitro of a TGF-beta3 dependent mechanism induced by low dose rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-beta3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation. PMID- 26673925 TI - Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review. AB - Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. PMID- 26673926 TI - Responding to the needs of refugees. PMID- 26673927 TI - Answer to the question 2 from page 362. PMID- 26673929 TI - Multi-agent System for Obtaining Relevant Genes in Expression Analysis between Young and Older Women with Triple Negative Breast Cancer. AB - Triple negative breast cancer is an aggressive form of breast cancer. Despite treatment with chemotherapy, relapses are frequent and response to these treatments is not the same in younger women as in older women. Therefore, the identification of genes that cause this difference is required. The identification of therapeutic targets is one of the sought after goals to develop new drugs. Within the range of different hybridization techniques, the developed system uses expression array analysis to measure the expression of the signal levels of thousands of genes in a given sample. Probesets of Gene 1.0 ST GeneChip arrays provide categorical genome transcript coverage, providing a measurement of the expression level of the sample. This paper proposes a multi-agent system to manage information of expression arrays, with the goal of providing an intuitive system that is also extensible to analyze and interpret the results. The roles of agent integrate different types of techniques, statistical and data mining methods that select a set of genes, searching techniques that find pathways in which such genes participate, and an information extraction procedure that applies a CBR system to check if these genes are involved in the disease. PMID- 26673928 TI - Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer's Disease. AB - Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional beta-amyloid deposition, or transient overcompensation during early stages of Alzheimer's disease. PMID- 26673930 TI - Discrimination of Brazilian propolis according to the seasoning using chemometrics and machine learning based on UV-Vis scanning data. AB - Propolis is a chemically complex biomass produced by honeybees (Apis mellifera) from plant resins added of salivary enzymes, beeswax, and pollen. The biological activities described for propolis were also identified for donor plant's resin, but a big challenge for the standardization of the chemical composition and biological effects of propolis remains on a better understanding of the influence of seasonality on the chemical constituents of that raw material. Since propolis quality depends, among other variables, on the local flora which is strongly influenced by (a)biotic factors over the seasons, to unravel the harvest season effect on the propolis' chemical profile is an issue of recognized importance. For that, fast, cheap, and robust analytical techniques seem to be the best choice for large scale quality control processes in the most demanding markets, e.g., human health applications. For that, UV-Visible (UV-Vis) scanning spectrophotometry of hydroalcoholic extracts (HE) of seventy-three propolis samples, collected over the seasons in 2014 (summer, spring, autumn, and winter) and 2015 (summer and autumn) in Southern Brazil was adopted. Further machine learning and chemometrics techniques were applied to the UV-Vis dataset aiming to gain insights as to the seasonality effect on the claimed chemical heterogeneity of propolis samples determined by changes in the flora of the geographic region under study. Descriptive and classification models were built following a chemometric approach, i.e. principal component analysis (PCA) and hierarchical clustering analysis (HCA) supported by scripts written in the R language. The UV Vis profiles associated with chemometric analysis allowed identifying a typical pattern in propolis samples collected in the summer. Importantly, the discrimination based on PCA could be improved by using the dataset of the fingerprint region of phenolic compounds (lambda = 280-400etam), suggesting that besides the biological activities of those secondary metabolites, they also play a relevant role for the discrimination and classification of that complex matrix through bioinformatics tools. Finally, a series of machine learning approaches, e.g., partial least square-discriminant analysis (PLS-DA), k-Nearest Neighbors (kNN), and Decision Trees showed to be complementary to PCA and HCA, allowing to obtain relevant information as to the sample discrimination. PMID- 26673932 TI - Integrating data from heterogeneous DNA microarray platforms. AB - DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID- 26673931 TI - UV-visible scanning spectrophotometry and chemometric analysis as tools for carotenoids analysis in cassava genotypes (Manihot esculenta Crantz). AB - In this study, the metabolomics characterization focusing on the carotenoid composition of ten cassava (Manihot esculenta) genotypes cultivated in southern Brazil by UV-visible scanning spectrophotometry and reverse phase-high performance liquid chromatography was performed. Cassava roots rich in beta carotene are an important staple food for populations with risk of vitamin A deficiency. Cassava genotypes with high pro-vitamin A activity have been identified as a strategy to reduce the prevalence of deficiency of this vitamin. The data set was used for the construction of a descriptive model by chemometric analysis. The genotypes of yellow-fleshed roots were clustered by the higher concentrations of cis-beta-carotene and lutein. Inversely, cream-fleshed roots genotypes were grouped precisely due to their lower concentrations of these pigments, as samples rich in lycopene (red-fleshed) differed among the studied genotypes. The analytical approach (UV-Vis, HPLC, and chemometrics) used showed to be efficient for understanding the chemodiversity of cassava genotypes, allowing to classify them according to important features for human health and nutrition. PMID- 26673933 TI - Extracting kinetic information from literature with KineticRE. AB - To better understand the dynamic behavior of metabolic networks in a wide variety of conditions, the field of Systems Biology has increased its interest in the use of kinetic models. The different databases, available these days, do not contain enough data regarding this topic. Given that a significant part of the relevant information for the development of such models is still wide spread in the literature, it becomes essential to develop specific and powerful text mining tools to collect these data. In this context, this work has as main objective the development of a text mining tool to extract, from scientific literature, kinetic parameters, their respective values and their relations with enzymes and metabolites. The approach proposed integrates the development of a novel plug-in over the text mining framework @Note2. In the end, the pipeline developed was validated with a case study on Kluyveromyces lactis, spanning the analysis and results of 20 full text documents. PMID- 26673934 TI - Father's death does not affect growth and maturation but hinders reproduction: evidence from adolescent girls in post-war Estonia. AB - The popular concept of predictive-adaptive responses poses that girls growing up without a father present in the family mature and start reproduction earlier because the father's absence is a cue for environmental harshness and uncertainty that favours switching to a precocious life-history strategy. Most studies supporting this concept have been performed in situations where the father's absence is caused by divorce or abandonment. Using a dataset of Estonian adolescent girls who had lost their fathers over the period of World War II, we show that father's death did not affect the rate of pubertal maturation (assessed on the basis of development of breasts and axillary hair) or growth. Father's death did not affect the age of first birth but, contrary to predictions, reduced lifetime reproductive success. Our findings thus do not support the concept of predictive-adaptive responses and suggest that alternative explanations for covariation between fatherlessness and early maturation are required. PMID- 26673935 TI - Predators modify the evolutionary response of prey to temperature change. AB - As climate regimes shift in many ecosystems worldwide, evolution may be a critical process allowing persistence in rapidly changing environments. Organisms regularly interact with other species, yet whether climate-mediated evolution can occur in the context of species interactions is not well understood. We tested whether a species interaction could modify evolutionary responses to temperature. We demonstrate that predation pressure by Dipteran larvae (Chaoborus americanus) modified the evolutionary response of a freshwater crustacean (Daphnia pulex) to its thermal environment over approximately seven generations in laboratory conditions. Daphnia kept at 21 degrees C evolved higher population growth rates than those kept at 18 degrees C, but only in those populations that were also reared with predators. Furthermore, predator-mediated selection resulted in the evolution of elevated Daphnia thermal plasticity. This laboratory natural selection experiment demonstrates that biotic interactions can modify evolutionary adaptation to temperature. Understanding the interplay between multiple selective forces can improve predictions of ecological and evolutionary responses of organisms to rapid environmental change. PMID- 26673936 TI - A novel form of spontaneous tool use displayed by several captive greater vasa parrots (Coracopsis vasa). AB - Parrots are frequently cited for their sophisticated problem-solving abilities, but cases of habitual tool use among psittacines are scarce. We report the first evidence, to our knowledge, of tool use by greater vasa parrots (Coracopsis vasa). Several members of a captive population spontaneously adopted a novel tool using technique by using pebbles and date pits either (i) to scrape on the inner surface of seashells, subsequently licking the resulting calcium powder from the tool, or (ii) as a wedge to break off smaller pieces of the shell for ingestion. Tool use occurred most frequently just prior to the breeding season, during which time numerous instances of tool transfer were also documented. These observations provide new insights into the tool-using capabilities of parrots and highlight the greater vasa parrot as a species of interest for studies of physical cognition. PMID- 26673938 TI - Ultrasound assessment of selected peripheral nerves pathologies. Part II: Entrapment neuropathies of the lower limb. AB - Similarly to entrapment neuropathies of upper extremities, the ultrasound constitutes a valuable supplementation of diagnostic examinations performed in patients with suspicions of nerve entrapment syndromes of the lower limb. For many years, it was claimed that such pathologies were rare. This probably resulted from the lack of proper diagnostic tools (including high frequency ultrasound transducers) as well as the lack of sufficient knowledge in this area. In relation to the above, the symptoms of compression neuropathies were frequently interpreted as a manifestation of pathologies of the lumbar part of the spine or a other orthopedic disease (degenerative or overuse one). Consequently, many patients were treated ineffectively for many months and even, years which led to irreparable neurological changes and changes in the motor organ. Apart from a clinical examination, the diagnostics of entrapment neuropathies of lower limb is currently based on imaging tests (ultrasound, magnetic resonance) as well as functional assessments (electromyography). Magnetic resonance imaging is characterized by a relatively low resolution (as compared to ultrasound) which results in limited possibilities of morphological evaluation of the visualized pathology. Electromyography allows for the assessment of nerve function, but does not precisely determine the type and degree of change. This article presents examples of the most common entrapment neuropathies of the lower limb concerning the following nerves: sciatic, femoral, lateral femoral cutaneous, obturator, fibular and its branches, tibial and its branches as well as sural. The pathomorphological basis of the neuropathies as well as corresponding ultrasound images are presented in this paper. Attention has been drawn to echogenicity, degree of vascularization and bundle presentation of the trunk of a pathological peripheral nerve. PMID- 26673937 TI - Symbiont transmission entails the risk of parasite infection. AB - Like many animals, firebugs (Hemiptera, Pyrrhocoridae) rely on behavioural adaptations to successfully endow their offspring with microbial mutualists. To transmit the nutritionally beneficial Coriobacteriaceae symbionts, female firebugs smear egg surfaces with symbiont-containing faecal droplets that are subsequently ingested by newly hatched nymphs through active probing to initiate infection. Alternatively, the symbionts can be acquired horizontally through contact with faeces of infected conspecifics. Here, we report that these adaptations ensuring successful transmission of bacterial symbionts among firebugs are exploited by the specialized trypanosomatid parasite Leptomonas pyrrhocoris. Using comparative transcriptomics, fluorescence in situ hybridization (FISH) and controlled bioassays, we demonstrate that the transmission cycle of L. pyrrhocoris mirrors that of the bacterial mutualists, with high efficiency for both vertical and horizontal transmission. This indicates that the parasite capitalizes on pre-existing behavioural adaptations (egg smearing and probing) to facilitate its own transfer within host populations, adaptations that likely evolved to initiate and maintain an association with beneficial gut symbionts. Thus, the transmission of mutualistic microbes across host generations can entail a significant risk of co-transmitting pathogens or parasites, thereby exerting selective pressures on the host to evolve more specific mechanisms of transfer. PMID- 26673939 TI - An association between neuropeptide Y levels and leukocyte subsets in stress exacerbated asthmatic mice. AB - Neuropeptide Y (NPY) was recently proposed to be associated with stress and airway inflammation; however, this has rarely been studied in animal models of asthma. Twenty-four C57BL/6 mice were randomly divided into 3 groups of 8 each: naive control group, asthma group (with an established asthma model), and stressed asthma group (with established asthma and stress models). Bronchoalveolar lavage (BAL) fluid was collected for total cell counts using a hemocytometer and for cytological examinations by Wright stain. Differential inflammatory cell counts were performed to identify eosinophils, macrophages, neutrophils, and lymphocytes. NPY and corticosterone serum levels were determined with enzyme immunoassay kits. Stress was associated with increased airway inflammatory response, which was manifested by the accumulation of total leukocytes and eosinophils in the BAL fluid in comparison with the asthma and the control groups. The levels of NPY (p<0.05) and corticosterone (p<0.01) were elevated in the stressed asthma group in comparison with the control and asthma groups. The concentration of NPY and corticosterone positively correlated with the total leukocyte count (r=0.892, p<0.05 and r=0.937, p<0.01 respectively) and eosinophil numbers (r=0.806, p=0.053 and r=0.885, p<0.01 respectively). Stress may be associated with elevated peripheral NPY level, which was observed to be associated with exacerbated airway inflammation in asthmatic mice. PMID- 26673940 TI - Concentration is not enough to evaluate accumulation of heavy metals and nutrients in plants. AB - Wetland plants produce high aboveground biomass and possess the ability to accumulate heavy metals and nutrients. This ability is used for phytoremediation purposes including removal of nutrients and heavy metals from polluted waters. The concentrations of heavy metals are usually much higher in the belowground then in aboveground biomass, especially in roots which are primary sites of uptake. This may lead to the conclusion that accumulation of heavy metals is higher in the belowground biomass. However, in case the aboveground is much higher than belowground biomass the accumulation could be higher in the aboveground biomass. Concentration of nitrogen and phosphorus is always higher in leaves than in stems. However, the stem biomass is often much higher in robust emergent species such as Phragmites australis and therefore, more nutrients can be stored in stems. The examples shown in this communication clearly reveal that to evaluate properly the accumulation of heavy metals and nutrients in particular plant compartment biomass amount must be taken into consideration. In the first study, concentrations of Cd, Cr and Hg in Phalaris arundinacea belowground/aboveground biomass were 150/80 MUg/kg, 5420/228 MUg/kg and 38/18 MUg/kg. The high aboveground biomass (1196 g/m(2)) and low belowground biomass (244 g/(2)) resulted in much higher accumulation of Cd and Hg in aboveground biomass (96 MUg/m(2) and 21.2 MUg/m(2), respectively) than in belowground biomass (36 MUg/m(2) and 9.3 MUg/m(2), respectively). Only for chromium, belowground accumulation (1312 MUg/m(2)) was higher than aboveground accumulation (272 MUg/m(2)). In the second study, both nitrogen and phosphorus concentrations were higher (26.7 mg/g and 749 mg/kg, respectively) in leaves than in stems (8.2mg/g and 534 mg/kg, respectively) of P. australis. The higher biomass of stems (1835 g/m(2)) than leaves (967 g/m(2)) resulted in higher accumulation of nitrogen but lower accumulation of phosphorus in leaves as compared to stems. PMID- 26673942 TI - Gluten Sensitivity - A Potentially Reversible Cause of Progressive Cerebellar Ataxia and Myoclonus - A Case Report. AB - Gluten sensitivity is an umbrella term used for diverse clinical manifestations occurring as a result of abnormal immunological reactivity to dietary gluten in genetically susceptible individuals. Celiac disease is the most well-known but not the only manifestation of gluten sensitivity. Myoclonus with Ataxia is a rare manifestation of gluten sensitivity and should be considered in the differential diagnosis of all patients with idiopathic sporadic ataxia. The presence of gluten related immune markers in normal population however complicates the reliable diagnosis of gluten related neurological disorders and clinical improvement on gluten free diet can serve as a diagnostic tool for this disease. We report a case of sporadic progressive cerebellar ataxia with myoclonus with positive antigliadin antibodies, which improved with a trial of gluten free diet. This case highlights an important diagnostic and therapeutic principle in management of late onset idiopathic ataxia. PMID- 26673943 TI - VUV-Photocatalytic Degradation of Bezafibrate by Hydrothermally Synthesized Enhanced {001} Facets TiO2/Ti Film. AB - In the present study, a novel TiO2/Ti film with enhanced {001} facets was synthesized by the hydrothermal technique followed by calcination for studying the removal of bezafibrate (BZF), from an aqueous environment. The synthesized photocatalyst was characterized by FE-SEM, XRD, HR-TEM, and PL-technique. The second-order rate constant of (*)OH with BZF was found to be 5.66 * 10(9) M(-1) s(-1). The steady state [(*)OH] was measured as 1.16 * 10(-11) M, on the basis of oxidation of terephthalic acid. The photocatalytic degradation of BZF followed pseudo-first-order kinetics according to the Langmuir-Hinshelwood model (k1 = 2.617 mg L(-1) min(-1) and k2 = 0.0796 (mg L(-1))(-1)). The effects of concentration and the nature of various additives including inorganic anions (NO3(-), NO2(-), HCO3(-), CO3(2-), Cl(-)) and organic species (fulvic acid) and initial solution pHs (2, 4, 6, 9) on photocatalytic degradation of BZF were investigated. It was found that the nature and concentration of studied additives significantly affected the photocatalytic degradation of BZF. The efficiency of the photocatalytic degradation process in terms of electrical energy per order was estimated. Degradation schemes were proposed on the basis of the identified degradation byproducts by ultraperformance liquid chromatography. PMID- 26673941 TI - Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization. AB - High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID- 26673944 TI - Involuntary attentional orienting in the absence of awareness speeds up early sensory processing. AB - A long-standing controversy in the field of human neuroscience has revolved around the question whether attended stimuli are processed more rapidly compared to unattended stimuli. We conducted two event-related potential (ERP) experiments employing a temporal order judgment procedure in order to assess whether involuntary attention accelerates sensory processing, as indicated by latency modulations of early visual ERP components. A non-reportable exogenous cue could precede the first target with equal probability at the same (compatible) or opposite (incompatible) location. The use of non-reportable cues promoted automatic, bottom-up attentional capture, and ensured the elimination of any confounds related to the use of stimulus features that are common to both cue and target. Behavioral results confirmed involuntary exogenous orienting towards the unaware cue. ERP results showed that the N1pc, an electrophysiological measure of attentional orienting, was smaller and peaked earlier in compatible as opposed to incompatible trials, indicating cue-dependent changes in magnitude and speed of first target processing in extrastriate visual areas. Complementary Bayesian analysis confirmed the presence of this effect regardless of whether participants were actively looking for the cue (Experiment 1) or were not informed of it (Experiment 2), indicating purely automatic, stimulus-driven orienting mechanisms. PMID- 26673945 TI - Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility. AB - Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum - VS, ventral tegmental area - VTA), motor (supplementary motor areas - SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex - mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex - lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex - dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control. PMID- 26673946 TI - Shifts in connectivity during procedural learning after motor cortex stimulation: A combined transcranial magnetic stimulation/functional magnetic resonance imaging study. AB - Inhibitory transcranial magnetic stimulation (TMS), of which continuous theta burst stimulation (cTBS) is a common form, has been used to inhibit cortical areas during investigations of their function. cTBS applied to the primary motor area (M1) depresses motor output excitability via a local effect and impairs procedural motor learning. This could be due to an effect on M1 itself and/or to changes in its connectivity with other nodes in the learning network. To investigate this issue, we used functional magnetic resonance imaging to measure changes in brain activation and connectivity during implicit procedural learning after real and sham cTBS of M1. Compared to sham, real cTBS impaired motor sequence learning, but caused no local or distant changes in brain activation. Rather, it reduced functional connectivity between motor (M1, dorsal premotor & supplementary motor areas) and visual (superior & inferior occipital gyri) areas. It also increased connectivity between frontal associative (superior & inferior frontal gyri), cingulate (dorsal & middle cingulate), and temporal areas. This potentially compensatory shift in coupling, from a motor-based learning network to an associative learning network accounts for the behavioral effects of cTBS of M1. The findings suggest that the inhibitory TMS affects behavior via relatively subtle and distributed effects on connectivity within networks, rather than by taking the stimulated area "offline". PMID- 26673948 TI - Enzymatic PEGylated Poly(lactone-co-beta-amino ester) Nanoparticles as Biodegradable, Biocompatible and Stable Vectors for Gene Delivery. AB - We have developed new, efficient gene delivery systems based on PEGylated poly(lactone-co-beta-amino ester) block copolymers that are biodegradable, stable and low in toxicity. The PEG-poly[PDL-co-3-(4-(methylene)piperidin-1 yl)propanoate] (PEG-PPM) diblock and PPM-PEG-PPM triblock copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of omega-pentadecalactone (PDL) and ethyl 3-(4-(hydroxymethyl)piperidin-1 yl)propanoate (EHMPP) with an appropriate PEG (MeO-PEG-OH or HO-PEG-OH). The amphiphilic block copolymers are capable of condensing DNA in aqueous medium via a self-assembly process to form polyplex micelle nanoparticles with desirable particle sizes (70-140 nm). These micelles possess low CMC values and are stable in the medium containing serum protein molecules (FBS). Among the PEG-PPM and PPM PEG-PPM micelles, the PEG-PPM-15% PDL micelle particles exhibited high DNA binding ability, the fastest cellular uptake rate and highest gene transfection efficacy. Flow cytometry analysis shows that LucDNA/PEG-PPM-15% PDL polyplex micelles can effectively escape from endosomal degradation after cellular uptake likely due to the presence of the tertiary amine groups in the copolymer chains that act as proton sponges. In vitro cytotoxicity and hemolysis assay experiments indicate that all copolymer samples are nonhemolytic and have minimal toxicity toward COS-7 cells within the polymer concentration range (<=200 MUg/mL) used for the gene transfection. These results demonstrate that the PEGylated poly(lactone co-beta-amino ester) block copolymers are promising new vectors for gene delivery applications. PMID- 26673949 TI - Using Akaike's information theoretic criterion in population analysis: a simulation study. AB - Akaike's information-theoretic criterion for model discrimination (AIC) is often stated to "overfit", i.e., it selects models with a higher dimension than the dimension of the model that generated the data. However, when no fixed dimensional correct model exists, for example for pharmacokinetic data, AIC, or its bias-corrected version (AICc) might be the selection criterion of choice if the objective is to minimize prediction error. The present simulation study was designed to assess the behavior of AICc when applying it to the analysis of population data, for various degrees of interindividual variability. The simulation study showed that, at least in a relatively simple mixed effects modeling context, minimal mean AICc corresponded to best predictive performance even in the presence of large interindividual variability. PMID- 26673947 TI - Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA. AB - The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production abilities, while left and right ventral anterior insula volumes correlated with ratings of aberrant eating behavior. These two FTD clinical variants show different patterns of insular sub-region atrophy in the left precentral dorsal anterior and bilateral ventral anterior regions, providing further evidence for the role of these sub-regions in speech production and social-emotional function. PMID- 26673950 TI - Pancreatic Cancer: Current Options for Diagnosis, Staging and Therapeutic Management. AB - BACKGROUND: Pancreatic cancer is characterized by frequently delayed diagnosis and aggressive tumor growth which hampers most of the current treatment modalities. This review aims to summarize the available evidence about the diagnostic and therapeutic aspects of resectable and non-resectable pancreatic cancer therapy. SUMMARY: Embedded in the concept of multimodal therapy, surgery plays the central role in the treatment of pancreatic cancer. With advantageous tumor characteristics and complete tumor resection as the most relevant positive prognostic factors, the detection of premalignant or early invasive lesions combined with safe and oncologic adequate surgery is the major therapeutic aim. Most pancreatic adenocarcinomas are locally advanced or metastatic when diagnosed and need to be treated by the combination of surgery and (radio)chemotherapy or by palliative chemotherapy. PMID- 26673951 TI - Preface: Minority Men's Health. PMID- 26673952 TI - The impact of meticillin-resistant Staphylococcus aureus on patients with advanced cancer and their family members: A qualitative study. AB - BACKGROUND: Little is known about the impact of meticillin-resistant Staphylococcus aureus on patients with advanced cancer, such as its impact on the quality of life of this vulnerable group. To date, research on meticillin resistant Staphylococcus aureus in the palliative care setting has had a quantitative focus. AIM: The purpose of this study was to explore the impact of a meticillin-resistant Staphylococcus aureus diagnosis on patients and their carers. DESIGN: This article reports upon a qualitative interview study of nine patients with advanced cancer and meticillin-resistant Staphylococcus aureus and nine family members (n = 18). Framework analysis was used to analyse the data. SETTING/PARTICIPANTS: Patients and family members of patients with advanced cancer either admitted to the specialist palliative care unit or receiving palliative care in the hospital setting, who had a laboratory confirmed diagnosis of meticillin-resistant Staphylococcus aureus colonisation, were considered for inclusion in the study. RESULTS: Four themes were identified using framework analysis: reactions to receiving a meticillin-resistant Staphylococcus aureus diagnosis, the need for effective communication of the meticillin-resistant Staphylococcus aureus diagnosis, the enigmatic nature of meticillin-resistant Staphylococcus aureus, and lessons to guide the future care of meticillin resistant Staphylococcus aureus patients. CONCLUSION: This article indicates that meticillin-resistant Staphylococcus aureus can have a significant impact on advanced cancer patients and their families. This impact may be underestimated, but early and careful face-to-face explanation about meticillin-resistant Staphylococcus aureus and its implications can help patients and their families to cope better with it. These findings should be considered when developing policy relating to meticillin-resistant Staphylococcus aureus management and infection control in specialist palliative care settings. PMID- 26673953 TI - Synthesis of 2-Keto(hetero)aryl Benzox(thio)azoles through Base Promoted Cyclization of 2-Amino(thio)phenols with alpha,alpha-Dihaloketones. AB - An interesting base-promoted protocol for the synthesis of 2-keto(hetero)aryl benzox(thi)azoles has been developed. Starting from commercially available 2 amino(thio)phenols and alpha,alpha-dihaloketones, moderate to good yields of the corresponding heterocycles can be achieved. Notably, only EtNH2 was required as the promoter here, and the reaction can be easily performed on a large scale. PMID- 26673954 TI - Reliability and Validity of the Meaningfulness of Songwriting Scale (MSS) with Adults on Acute Psychiatric and Detoxification Units. AB - BACKGROUND: Songwriting is an intervention with demonstrated clinical benefit for a range of clinical populations. Researchers argue that positive outcomes are in part the result of the meaningfulness of the creative process. However, no measure currently exists to quantify the extent of meaning derived from songwriting processes. OBJECTIVE: To psychometrically evaluate the Meaningfulness of Songwriting Scale (MSS) as a measure of meaning of a therapeutic songwriting process. METHOD: 147 participants receiving short-term mental health care (39 acute psychiatric care; 108 detoxification unit) were asked to complete the MSS and the Short State Flow Scale immediately following a songwriting music therapy session. Six hours later, participants completed the MSS a second time. Analyses were performed by participant cohort to determine the content validity, internal consistency, test-retest reliability, measurement error, and construct validity. RESULTS: Findings indicated that the MSS has good content validity, strong internal consistency (alpha = 0.98, acute psychiatric group, and alpha = 0.96, detoxification group), acceptable test-retest reliability (ICC2,1 = 0.93, acute psychiatric group, and ICC2,1 = 0.89, detoxification group), and construct validity (acute group was r = 0.68, p < 0.001, and detoxification group was r = 0.56, p < 0.001). Measurement error was greater in the detoxification group, suggesting that the measure may be unstable for this group. CONCLUSIONS: Preliminary evidence supports MSS use for research with inpatients on acute psychiatric units; however, cautious use is recommended for use with inpatients in detoxification units due to measurement error. PMID- 26673955 TI - The Music Attentiveness Screening Assessment, Revised (MASA-R): A Study of Technical Adequacy. AB - BACKGROUND: Evidence suggests that attention is an important consideration when designing procedural support interventions for children undergoing distressing medical procedures. As such, the extent to which children can attend to musical stimuli used during music-based procedural support interventions would seem important. The Music Attentiveness Screening Assessment (MASA) was designed to assess a child's ability to attend to musical stimuli, but further revisions were deemed necessary to improve administration, test-retest reliability, and interobserver agreement for the measure's items. OBJECTIVE: This study investigated the technical adequacy of the Music Attentiveness Screening Assessment, Revised (MASA-R), with a non-clinical sample of children aged 4 to 9 years by examining (a) Construct validity using comparator instruments measuring auditory attention; (b) Test-retest reliability following a two-week delay; and (c) Interobserver agreement when administered by two independent examiners. METHODS: This non-clinical sample included 69 children who were administered both items from MASA-R and two comparator instruments: the Auditory Attention subtest from the NEPSY-II (NII-AA) for children aged 5 to 9 years (n = 47); and the Auditory Attention subtest from the Woodcock-Johnson Tests of Cognitive Abilities, 3rd ed. (WJIII-AA), for children aged 4 years (n = 22). RESULTS: A significant proportion of score variance was shared by both MASA-R items and the comparator measures: R (2) = .16, F(2, 66) = 6.30, p = .003. MASA-R score estimates with regard to test-retest reliability (Item I, intra-class correlation [ICC] = .88; Item II, ICC = .91) and interobserver agreement (Item I, ICC = .99; Item II, ICC = .98) also fell into acceptable ranges. CONCLUSIONS: Estimates of MASA-R score construct validity, test-retest reliability, and interobserver agreement appear improved over its predecessor, MASA. While findings are promising, additional investigation of its use with a clinical sample is needed before it can be confidently used in pediatrics. PMID- 26673956 TI - Performative, Arts-Based, or Arts-Informed? Reflections on the Development of Arts-Based Research in Music Therapy. AB - Arts-based research (ABR) has emerged in music therapy in diverse ways, employing a range of interpretive paradigms and artistic media. It is notable that no consensus exists as to when and where the arts are included in the research process, or which music therapy topics are most suited to arts-based study. This diversity may pose challenges for music therapists who are developing, reading, and evaluating arts-based research. This paper provides an updated review of arts based research literature in music therapy, along with four questions for researchers who are developing arts-based research. These questions are 1) When should the arts be introduced? 2) Which artistic medium is appropriate? 3) How should the art be understood? and 4) What is the role of the audience? We argue that these questions are key to understanding arts-based research, justifying methods, and evaluating claims arising from arts-based research. Rather than defining arts-based research in music therapy, we suggest that arts-based research should be understood as a flexible research strategy appropriate for exploring the complexities of music therapy practice. PMID- 26673957 TI - Accumulation Mechanisms of CD4(+)CD25(+)FOXP3(+) Regulatory T Cells in EBV associated Gastric Carcinoma. AB - Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV) and are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are known to be accompanied by massive CD8(+) cytotoxic T cell (CTL) infiltration; however, adoptive cellular immunotherapy based on EBV-specific CD8(+) CTLs has been explored with limited success. Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, we assessed the distribution of Tregs in 45 cases of EBVaGC and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. We showed that Tregs were significantly increased in EBVaGC compared to EBVnGC (15.92 +/- 11.45/HPF vs. 8.45 +/- 6.16/HPF, p = 0.001). In addition, we explored the accumulation mechanisms of Tregs in EBVaGC by using EBV (+) gastric carcinoma cell lines SNU719 and GT39 as ex vivo models. When peripheral blood mononuclear cells (PBMCs) were co-cultured with EBV (+) gastric carcinoma cell lines, the Treg frequency increased, and they underwent phenotypic and functional changes. The enhanced recruitment by CCL22 produced by EBVaGC cells, the decreased emigration due to CCR7 downregulation on the Treg surface, the higher proliferation rate, and the lower apoptosis rate of Tregs at tumour sites may promote the accumulation of Tregs in EBVaGC. PMID- 26673958 TI - Infection in an aging population. AB - The global population is rapidly aging. Currently, 566 million people are >=65 years old worldwide, with estimates of nearly 1.5 billion by 2050, particularly in developing countries. Infections constitute a third of mortality in people >=65 years old. Moreover, lengthening life spans correlate with increased time in hospitals or long-term care facilities and exposure to drug-resistant pathogens. Indeed, the risk of nosocomial infections increases with age, independent of duration spent in healthcare facilities. In this review, we summarize our understanding of how the aging immune system relates to bacterial infections. We highlight the most prevalent infections affecting aging populations including pneumonia, urinary tract infections, and wound infections and make recommendations for future research into infection in aging populations. PMID- 26673959 TI - A misleading feeling of happiness: metamemory for positive emotional and neutral pictures. AB - Emotional information is often remembered better than neutral information, but the emotional benefit for positive information is less consistently observed than the benefit for negative information. The current study examined whether positive emotional pictures are recognised better than neutral pictures, and further examined whether participants can predict how emotion affects picture recognition. In two experiments, participants studied a mixed list of positive and neutral pictures, and made immediate judgements of learning (JOLs). JOLs for positive pictures were consistently higher than for neutral pictures. However, recognition performance displayed an inconsistent pattern. In Experiment 1, neutral pictures were more discriminable than positive pictures, but Experiment 2 found no difference in recognition based on emotional content. Despite participants' beliefs, positive emotional content does not appear to consistently benefit picture memory. PMID- 26673960 TI - Theoretical insights into a potential lead-free hybrid perovskite: substituting Pb(2+) with Ge(2.). AB - In recent years, perovskite solar cells have been considerably developed, however the lead in the absorber MAPbI3 is a potential threat to the environment. To explore potential alternatives, the structural and electronic properties of MAGeX3 (X = Cl, Br, I) were investigated using different density functional theory methods, including GGA-PBE, PBE-SOC, HSE06 and HSE-SOC. The results implied that MAGeI3 exhibits an analogous band gap, substantial stability, remarkable optical properties, and significant hole and electron conductive behavior compared with the so far widely used absorber MAPbI3. Moreover, the calculations revealed that the energy splitting resulting from the spin-orbit coupling is evident on Pb, moderate on Ge, I and Br, and negligible on Cl. Our work not only sheds some light on screening novel absorbers for perovskite solar cells but also deepens the understanding of these functional materials. PMID- 26673962 TI - Ultrasound quiz. PMID- 26673961 TI - Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients. AB - BACKGROUND: Serum profiling using mass spectrometry-based proteomic techniques has great potential to detect biomarkers that might improve the management for advanced breast cancer patients. The albuminome has previously been investigated as a tool in biomarker discovery, however other high abundant blood proteins are also likely to sequester potentially interesting molecules. METHODS: Affinity resin purified and isolated Transferrin and associated bound proteins from normal control and breast cancer patient serum samples were analysed by label-free mass spectrometry during the discovery phase. RESULTS: 21 significant proteins were identified with Fibrinogen and Fibronectin selected for further analysis in an independent sample set, with significant difference found when comparing the controls groups (normal healthy control, inflammatory bowel disease and benign breast disease) to stage IV breast cancer. CONCLUSIONS: The area under the curve value for Fibrinogen compared favourably with cancer antigen 15-3, an established breast cancer tumour marker. A combination of all three biomarkers improved accuracy when comparing control/benign to stage IV breast cancer patient groups. GENERAL SIGNIFICANCE: Mass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence. PMID- 26673963 TI - Roquin--a multifunctional regulator of immune homeostasis. AB - Roquin-1 (Rc3h1) is an E3 ubiquitin ligase originally discovered in a mutational screen for genetic factors contributory to systemic lupus erythematosus-like symptoms in mice. A single base-pair mutation in the Rc3h1 gene resulted in the manifestation of autoantibody production and sustained immunological inflammation characterized by excessive T follicular helper cell activation and formation of germinal centers. Subsequent studies have uncovered a multifactorial process by which Roquin-1 contributes to the maintenance of immune homeostasis. Through its interactions with partner proteins, Roquin-1 targets mRNAs for decay with inducible costimulator being a primary target. In this review, we discuss newly discovered functions of Roquin-1 in the immune system and inflammation, and in disease manifestation, and discuss avenues of further research. A model is presented for the role of Roquin in health and disease. PMID- 26673964 TI - Alterations of the immunosuppressive IL4I1 enzyme activity induced by naturally occurring SNP/mutations. AB - The immunosuppressive phenylalanine oxidase interleukin 4-induced gene 1 (IL4I1), primarily produced by antigen-presenting cells, inhibits T-cell proliferation and promotes the generation of Foxp3(+) regulatory T cells in vitro. Highly expressed by tumour-associated macrophages from human cancers, IL4I1 has a potential role in immune evasion from the anti-tumour immune response. We have reviewed single nucleotide polymorphisms (SNPs) and mutations described for the exon 4 of the IL4I1 isoform 1, which is expressed in lymphoid tissue. Two of them were expressed in an exogenous system to analyse their effect on the enzymatic activity. The N92D SNP leads to a hyperactive enzyme, while the R102G mutation is hypomorphic. Moreover, we show that IL4I1 activity is not only directed against phenylalanine, as initially described, but also at a lower level against arginine. These data pave the way to more extensive analyses of the mutational state of IL4I1 in pathological conditions such as cancer, where its participation in immune system dysfunctions may have therapeutic implications. PMID- 26673965 TI - Variability at the FCGR locus: characterization in Black South Africans and evidence for ethnic variation in and out of Africa. AB - This study set out to comprehensively investigate all known functional FcgammaR variants in South African Black and Caucasian individuals. Population diversity was further assessed using data from the 1000 Genomes Project. In our cohort, Black South Africans neither possessed the haplotypes previously associated with increased surface densities of FcgammaRIIb and FcgammaRIIIa nor the FCGR2C haplotype recently associated with increased vaccine efficacy in the RV144 HIV-1 vaccine trial (despite 48.7% bearing the c.134-96T tag allele). Moreover, Africans (South Africans, Luhya Kenyans and Yoruba Nigerians) lack the FCGR2C c.798+1G splice-site allele required for the expression of functional FcgammaRIIc. Although the presence or absence of surface FcgammaRIIc did not affect natural killer cell-mediated antibody-dependent cellular cytotoxicity capability, this may be significant for other FcgammaRIIc-mediated functions. Overall, allele distribution and linkage disequilibrium in Africans and Caucasians differed in a manner that would suggest a differentially maintained balance of FcgammaR-mediated cell activation in these populations. Finally, significant variation observed among different African populations precludes the use of any one African population as a proxy for FcgammaR diversity in Africans. In conclusion, the findings of this study highlight further ethnic variation at the FCGR gene locus, in particular for FCGR2C, a gene with increasingly recognized clinical significance. PMID- 26673967 TI - Decreased level of serum autoantibody against LG72 is a biosignature of amyotrophic lateral sclerosis. AB - AIM: LG72 can increase mitochondrial ROSs and oxidative stress has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). The serum level of LG72 or LG72-related molecules might therefore be associated with ALS. Here, we aim to determine the serum autoantibody against LG72 has potential as a biomarker for the diagnosis of ALS. MATERIALS: Seventy-eighty patients with ALS, 45 patients with AD, 43 patients with PD and 88 healthy adults were enrolled. RESULTS: The concentration of serum autoantibody against LG72 was more than fourfold lower in ALS than other control groups (p < 0.001). The AUC was 0.9627 when the cut-off value for autoantibody concentration was 0.167 MUg/ml. CONCLUSION: This finding suggests that the autoantibody against LG72 might serve as a surrogate biomarker for ALS. PMID- 26673966 TI - A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels. AB - Long non-coding RNAs (lncRNAs) can regulate the transcript levels of genes in the same genomic region. These locally acting lncRNAs have been found deregulated in human disease and some have been shown to harbour quantitative trait loci (eQTLs) in autoimmune diseases. However, lncRNAs linked to the transcription of candidate risk genes in loci associated to rheumatoid arthritis (RA) have not yet been identified. The TRAF1 and C5 risk locus shows evidence of multiple eQTLs and transcription of intergenic non-coding sequences. Here, we identified a non coding transcript (C5T1lncRNA) starting in the 3' untranslated region (UTR) of C5. RA-relevant cell types express C5T1lncRNA and RNA levels are further enhanced by specific immune stimuli. C5T1lncRNA is expressed predominantly in the nucleus and its expression correlates positively with C5 mRNA in various tissues (P=0.001) and in peripheral blood mononuclear cells (P=0.02) indicating transcriptional co-regulation. Knockdown results in a concurrent decrease in C5 mRNA levels but not of other neighbouring genes. Overall, our data show the identification of a novel lncRNA C5T1lncRNA that is fully located in the associated region and influences transcript levels of C5, a gene previously linked to RA pathogenesis. PMID- 26673968 TI - Screening of Peroxisome Proliferator-Activated Receptors (PPARs) alpha, gamma and alpha Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population. AB - OBJECTIVE: This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes PPARalpha L162V, PPARgamma2 C161T and PPARdelta T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia. METHODS: Socio-demographic data, anthropometric and biochemical measurements (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians). RESULTS: The overall minor allele frequencies were .08, .22 and .30 for PPAR alpha L162V, gamma C161T, delta T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by chi(2) analysis, ethnicity-stratified and logistic regression analyses. Nevertheless, participants with V162 allele of PPARalpha had significantly higher IL-6, while those with T161 allele of PPARgamma2 had significantly lower HOMA-IR. CONCLUSIONS: All PPAR SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malaysia, where only PPARalpha V162 and PPARgamma2 T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively. PMID- 26673969 TI - 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim. AB - Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6 GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6 GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats. PMID- 26673970 TI - Orientation-distribution mapping of polycrystalline materials by Raman microspectroscopy. AB - Raman microspectroscopy provides the means to obtain local orientations on polycrystalline materials at the submicrometer level. The present work demonstrates how orientation-distribution maps composed of Raman intensity distributions can be acquired on large areas of several hundreds of square micrometers. A polycrystalline CuInSe2 thin film was used as a model system. The orientation distributions are evidenced by corresponding measurements using electron backscatter diffraction (EBSD) on the same identical specimen positions. The quantitative, local orientation information obtained by means of EBSD was used to calculate the theoretical Raman intensities for specific grain orientations, which agree well with the experimental values. The presented approach establishes new horizons for Raman microspectroscopy as a tool for quantitative, microstructural analysis at submicrometer resolution. PMID- 26673971 TI - Intact implicit processing of facial threat cues in schizophrenia. AB - An emerging body of research suggests that people with schizophrenia retain the ability to implicitly perceive facial affect, despite well-documented difficulty explicitly identifying emotional expressions. It remains unclear, however, whether such functional implicit processing extends beyond emotion to other socially relevant facial cues. Here, we constructed two novel versions of the Affect Misattribution Procedure, a paradigm in which affective responses to primes are projected onto neutral targets. The first version included three face primes previously validated to elicit varying inferences of threat from healthy individuals via emotion-independent structural modification (e.g., nose and eye size). The second version included the threat-relevant emotional primes of angry, neutral, and happy faces. Data from 126 participants with schizophrenia and 84 healthy controls revealed that although performing more poorly on an assessment of explicit emotion recognition, patients showed normative implicit threat processing for both non-emotional and emotional facial cues. Collectively, these results support recent hypotheses postulating that the initial perception of salient facial information remains intact in schizophrenia, but that deficits arise at subsequent stages of contextual integration and appraisal. Such a breakdown in the stream of face processing has important implications for mechanistic models of social cognitive impairment in schizophrenia and treatment strategies aiming to improve functional outcome. PMID- 26673972 TI - Anticipation and experience of emotions in patients with schizophrenia and negative symptoms. An experimental study in a social context. AB - Negative symptoms play a central role in the impairment of social functioning in schizophrenia. Healthy individuals use anticipated emotions to guide their decisions to seek out social interactions. It is unknown whether social withdrawal in negative symptoms is related to a biased anticipation of emotions that will arise in social situations. This study thus examined differences between patients with negative symptoms of schizophrenia and healthy controls in the anticipation and experience of positive and negative emotions related to a social interaction. In a between-subject factorial design, participants were instructed to either predict or to experience emotions related to a simulated social inclusion and exclusion interaction. Overall, patients anticipated more intense negative emotions than controls. Divided by the type of social situation, however, patients reported less intense positive emotions than controls with regard to social inclusion, but not with regard to social exclusion. The lack of an overall deficit in anticipation of positive emotions speaks against the assumption that anticipation abnormalities in negative symptoms are due to a neurocognitive deficit. Rather, the findings seem to reflect negative beliefs about potentially rewarding social situations in people with negative symptoms. PMID- 26673973 TI - Declining transition rates to psychotic disorder in "ultra-high risk" clients: Investigation of a dilution effect. AB - During recent years, a decrease has been noted in the rate of transition of ultra high risk (UHR) clients to a psychotic disorder. Although important to the concept of the at-risk mental state, the reasons for this decline remain largely unknown. We investigated the possibility of a 'dilution effect' in contributing to the decline, i.e. if later UHR cohorts present with less severe clinical intake characteristics than earlier cohorts. Firstly, clinical intake characteristics of a large UHR sample (n=397) were compared across baseline year epochs (1995-2006). Characteristics showing significant differences were included in a Cox-regression to examine if they could explain the decline in transition rates. Secondly, because later cohorts show lower transition rates, 'more stringent' UHR-criteria were retrospectively applied to these cohorts (post-2000, n=219), investigating if this resulted in a higher transition rate. Results indicated that earlier cohorts presented with (1) a larger array of attenuated psychotic symptoms, (2) higher ratings on conceptual disorganization (formal thought disorder) and (3) a higher proportion of individuals with trait risk factor (all P<.001). However, these factors could not fully account for the decline in transition rates. Applying more stringent UHR-criteria to the post 2000-subsample did not substantially change the rate of transition. Our study suggests that later UHR cohorts presented with different clinical intake characteristics than earlier cohorts. While this may have contributed to the observed decrease in transition rates to psychosis, it does not appear to fully account for this decline, suggesting other factors have also impacted on transition rates over time. PMID- 26673974 TI - The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part I and II. PMID- 26673976 TI - Kernel Target Alignment Parameter: A New Modelability Measure for Regression Tasks. AB - In this paper, we demonstrate that the kernel target alignment (KTA) parameter can efficiently be used to estimate the relevance of molecular descriptors for QSAR modeling on a given data set, i.e., as a modelability measure. The efficiency of KTA to assess modelability was demonstrated in two series of QSAR modeling studies, either varying different descriptor spaces for one same data set, or comparing various data sets within one same descriptor space. Considered data sets included 25 series of various GPCR binders with ChEMBL-reported pKi values, and a toxicity data set. Employed descriptor spaces covered more than 100 different ISIDA fragment descriptor types, and ChemAxon BCUT terms. Model performances (RMSE) were seen to anticorrelate consistently with the KTA parameter. Two other modelability measures were employed for benchmarking purposes: the Jaccard distance average over the data set (Div), and a measure related to the normalized mean absolute error (MAE) obtained in 1-nearest neighbors calculations on the training set (Sim = 1 - MAE). It has been demonstrated that both Div and Sim perform similarly to KTA. However, a consensus index combining KTA, Div and Sim provides a more robust correlation with RMSE than any of the individual modelability measures. PMID- 26673975 TI - Microdroplet photobioreactor for the photoautotrophic culture of microalgal cells. AB - Microalgae, unicellular photoautotrophic microorganisms, have attracted great attention for the production of biofuel and high-value products, but the commercial use of microalgae has been limited by low photosynthetic productivity. To overcome this limitation, it is required to develop an efficient platform for the rapid evaluation of photoautotrophic growth performance and productivity of microalgal strains. Here we describe a droplet-based photobioreactor for high throughput analysis of the photoautotrophic growth of microalgal cells. By integrating micropillar arrays and adjusting the height of the microchamber, we could accurately monitor the growth kinetics of microalgae in an immobilized microdroplet and improve the transfer rate of CO2 into the microdroplet photobioreactor with an increased contact area between the microdroplet and PDMS surface. The improvement of CO2 transfer into the microdroplet was also confirmed by improved microalgal cell growth and a decrease in pH measured using colorimetric and fluorescence-based assays. The photoautotrophic growth kinetics of Chlorella vulgaris were measured under different CO2 concentrations (ambient, 1%, 2.5%, 5% and 7.5%) and light intensity (35, 55, 100, 150, and 200 MUmol photons per m(2) per s) conditions, which are key factors for photoautotrophic growth. Chlorella vulgaris in a microdroplet showed better cell growth performance compared to a flask culture due to the reduced shading effects and improved mass transfer. Finally, we could evaluate the photoautotrophic growth performance of four microalgal strains (Chlorella vulgaris, Chlorella protothecoides, Chlorella sorokiniana and Neochloris oleoabundans) for 120 hours. These results demonstrate that our microdroplet system can be used as an efficient photobioreactor for the rapid evaluation of the photoautotrophic growth of microalgal strains under various conditions. PMID- 26673977 TI - The effects of plane and arc of elevation on electromyography of shoulder musculature in patients with rotator cuff tears. AB - BACKGROUND: Arm elevations in different planes are commonly assessed in clinics and are included in rehabilitation protocols for patients with rotator cuff pathology. The aim of this study was to quantify the effect of plane and angle of elevation on shoulder muscles activity in patients with symptomatic rotator cuff tear to be used for rehabilitation purposes. METHODS: Eight symptomatic patients with rotator cuff tears were assessed by using EMG (11 surface and 2 fine wire electrodes) synchronized with a motion analysis. The subjects completed five elevations in full can position (arm externally rotated and thumb up) in frontal, scapular and sagittal planes. Muscle activity in three elevation arcs of 20 degrees (from 0 degrees to 60 degrees ) was presented as the percentage of mean activity. Data were analyzed by mixed linear models (alpha=0.003), and Tuckey Post-hoc comparisons for significant effects (alpha=0.05). FINDINGS: The effect of plane was significant for supraspinatus, middle trapezius, anterior, middle, and posterior deltoid, triceps, and pectoralis major (P<0.001). Supraspinatus was more active during abduction than scaption and flexion (P<0.05), and its activity did not increase significantly after 40 degrees of elevation (P>0.05). Infraspinatus had similar activity pattern in the three planes of elevation (P>0.003) with increasing trend in accordance with the elevation angle. INTERPRETATION: In any rehabilitation protocol, if less activity of supraspinatus is desired, active arm elevation should be directed toward flexion and scaption and postponed abduction to prevent high level of activity in this muscle. PMID- 26673978 TI - Assessment of the Sheffield Support Snood, an innovative cervical orthosis designed for people affected by neck muscle weakness. AB - BACKGROUND: This study aimed at quantifying the biomechanical features of the Sheffield Support Snood, a cervical orthosis specifically designed for patients with neck muscle weakness. The orthosis is designed to be adaptable to a patient's level of functional limitation using adjustable removable supports, which contribute support and restrict movement only in desired anatomical planes. METHODS: The snood was evaluated along with two commercially available orthoses, the Vista and Headmaster, in a series of flexion, extension, axial-rotation and lateral flexion movements. Characterization was performed with twelve healthy participants with and without the orthoses. Two inertial-magneto sensors, placed on the forehead and sternum, were used to quantify the neck's range of motion. FINDINGS: In its less supportive configuration, the snood was effective in limiting movements to the desired planes, preserving free movement in other planes. The Headmaster was only effective in limiting flexion. The range of motion achieved with the snood in its rigid configuration was equivalent (P>0.05, effect size<0.4) to that achieved with the Vista, both in trials performed reaching the maximum amplitude (range of motion reduction: 25%-34% vs 24%-47%) and at maximum speed (range of motion reduction: 24%-29% vs 25%-43%). INTERPRETATION: The Sheffield Support Snood is effectively adaptable to different tasks and, in its most supportive configuration, offers a support comparable to the Vista, but providing a less bulky structure. The chosen method is suitable for the assessment of range of motions while wearing neck orthoses and is easily translatable in a clinical context. PMID- 26673979 TI - Prognostic Factors in the Outcome of Invasive Fungal Sinusitis in a Pediatric Population. AB - BACKGROUND: Pediatric invasive fungal sinusitis (IFS) is rare, and its prognosticators are poorly understood. The aim of this study was to determine important factors affecting outcome. METHODS: A 10-year retrospective review at a tertiary academic children's hospital was performed using an International Classification of Diseases, 9th revision, and a procedure-based search after institutional review board approval. All relevant demographic and clinical information was collected. RESULTS: Fourteen immune-compromised patients (male:female = 7:7, mean age = 10 years, range 2-16 years) were identified who had hematologic malignancies (11), diabetes mellitus (2) and unknown predisposing factors (1). Fungal species included Aspergillus (5), Mucor (5), Alternaria (2), Rhizopus (1) and Scopulariopsis (1). The cohort underwent an average of 6.1 (median = 5) endoscopic sinus surgeries and were treated with aggressive antifungal therapy. Four deaths occurred in the study population: 2 were attributable to IFS and 2 attributable to their underlying malignancies. There was a significant difference in the median absolute neutrophil count (ANC) at follow-up after treatment of IFS between the survival and the mortality subgroups, with ANC being 4290.5 and 169, respectively (P < 0.001). CONCLUSIONS: Despite the small sample size, this study represents the largest case series in the medical literature on pediatric IFS. Age, gender, underlying cause for immunodeficiency and mycologic agent were not important prognosticators. ANC appears to be the only factor responsible for survival. The role of endoscopic sinus surgeries in survival is indeterminate. PMID- 26673980 TI - Subcutaneous Colletotrichum truncatum Infection in a Child. AB - Human infection with Colletotrichum species is typically limited to ophthalmologic manifestations. We present the first reported pediatric case of subcutaneous Colletotrichum truncatum infection. This case highlights the potential importance of C. truncatum as an agent of subcutaneous or disseminated disease in immunocompromised children. PMID- 26673981 TI - Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin. AB - Forty-three patients with Kawasaki disease who were resistant to initial intravenous immunoglobulin (IVIG) were randomized to receive either a second dose of IVIG (n = 32) or an infliximab (n = 11). With IVIG retreatment 21 patients (65.6%) responded, and with infliximab 10 patients (90.9%) responded. The infliximab group had shorter duration of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar. PMID- 26673982 TI - Roll-Plate Alone Does Not Demonstrate Colonization In Silicone Neonatal Catheters. AB - We compared roll-plate, sonication and slicing for the detection of colonization and catheter-related bloodstream infection (C-RBSI) in 90 silicone neonatal peripherally inserted central catheters. Colonization was detected by roll-plate, sonication and slicing in 3.4%, 6.9% and 10.3% of catheters, respectively. C-RBSI was detected by roll-plate, sonication and slicing only in 4.8% of each. The roll plate technique was not a good predictor of colonization and C-RBSI in silicone neonatal peripherally inserted central catheters. Detecting intraluminal colonization was required. PMID- 26673983 TI - Attachment organization in Arabic-speaking refugees with post traumatic stress disorder. AB - As a part of an ongoing clinical study of refugees with post traumatic stress disorder (PTSD), the primary objective of the current study was to examine and describe the distribution of adult attachment patterns as assessed by the Adult Attachment Interview (AAI) in Arabic-speaking refugees. A total of 43 adult male and female refugees with Iraqi and Palestinian backgrounds completed the AAI. Sixty-seven percent of the sample was classified as Unresolved with respect to loss or trauma and a substantial proportion of insecure attachment representations (14% Secure-Autonomous, 39% Dismissing, 42% Preoccupied, 5% Cannot Classify) was found, in addition to high intake levels of post traumatic stress symptoms and comorbidity. Findings are compared with AAI studies of other PTSD or trauma samples, and the paper elaborates upon the methodological challenges in administering the AAI in a context of simultaneous translation. PMID- 26673984 TI - Rare Enlargement of Genial Tubercles and its Management: A Case Report. AB - Genial tubercles are tiny bony projections located bilaterally around the lingual foramen, on the lingual surface of the mandible giving attachment to geniohyoid inferiorly & genioglossus superiorly. Due to delayed prosthetic rehabilitation & lack of balanced mastication excessive resorption of alveolar processes take place thereby leaving genial tubercles as elevated bony projections. This may pose problems in speech, deglutition & prosthetic rehabilitation. Excessive mobility of tongue may also contribute to enlargement of genial tubercles to such an extent that they may extend beyond the crest of alveolar ridges leaving them vulnerable to spontaneous fracture. This report presents a rare case of excessive enlargement of genial tubercles and its surgical management using a novel technique. This technique not only addresses the removal of the enlarged genial tubercles but also aims at reattachment of muscles attached to these tubercles, in a simple non morbid manner. PMID- 26673985 TI - Patient experiences with self-monitoring renal function after renal transplantation: results from a single-center prospective pilot study. AB - BACKGROUND: After a kidney transplantation, patients have to visit the hospital often to monitor for early signs of graft rejection. Self-monitoring of creatinine in addition to blood pressure at home could alleviate the burden of frequent outpatient visits, but only if patients are willing to self-monitor and if they adhere to the self-monitoring measurement regimen. A prospective pilot study was conducted to assess patients' experiences and satisfaction. MATERIALS AND METHODS: For 3 months after transplantation, 30 patients registered self measured creatinine and blood pressure values in an online record to which their physician had access to. Patients completed a questionnaire at baseline and follow-up to assess satisfaction, attitude, self-efficacy regarding self monitoring, worries, and physician support. Adherence was studied by comparing the number of registered with the number of requested measurements. RESULTS: Patients were highly motivated to self-monitor kidney function, and reported high levels of general satisfaction. Level of satisfaction was positively related to perceived support from physicians (P<0.01), level of self-efficacy (P<0.01), and amount of trust in the accuracy of the creatinine meter (P<0.01). The use of both the creatinine and blood pressure meter was considered pleasant and useful, despite the level of trust in the accuracy of the creatinine device being relatively low. Trust in the accuracy of the creatinine device appeared to be related to level of variation in subsequent measurement results, with more variation being related to lower levels of trust. Protocol adherence was generally very high, although the range of adherence levels was large and increased over time. CONCLUSION: Patients' high levels of satisfaction suggest that at-home monitoring of creatinine and blood pressure after transplantation offers a promising strategy. Important prerequisites for safe implementation in transplant care seem to be support from physicians and patients' confidence in both their own self-monitoring skills and the accuracy of the devices used. PMID- 26673986 TI - Medicare Utilization of Vascular Ultrasound From 1998 to 2013: Continued Growth in Both Radiologist and Nonradiologist Imaging. AB - PURPOSE: The aim of this study was to assess national trends in the utilization of vascular ultrasound (VUS) and changing relative specialty roles in examination interpretation. METHODS: Service-specific claims data for VUS studies were identified using Medicare Physician Supplier Procedure Summary Master Files for the period from 1998 to 2013. Longitudinal national utilization rates were calculated using annual Medicare enrollment data for 1998 to 2012. Procedure volumes by specialty group and site of service were analyzed. RESULTS: Total annual claims for VUS studies for Medicare fee-for-service beneficiaries increased from 4,422,360 to 8,599,677 (+94.5%) between 1998 and 2013. Per 1,000 beneficiaries, overall utilization rose from 145.93 in 1998 to 264.26 in 2012 (+81.1%). However, this peaked in 2009 at 270.43 and has been slowly declining each year since. Overall market share decreased from 43% to 41% for radiology and increased from 10% to 16% and from 9% to 17% for vascular surgery and cardiology, respectively. Compound adjusted growth rate increases were 4.2% for radiology, 7.8% for vascular surgery, and 8.7% for cardiology. CONCLUSIONS: Utilization of VUS in the Medicare population increased from 1998 through 2009 but has been declining ever since. Although radiology has maintained the dominant market share over time, relative growth by cardiology and vascular surgery has outpaced that by radiology. PMID- 26673987 TI - CHANGES IN PATELLOFEMORAL JOINT STRESS DURING RUNNING WITH THE APPLICATION OF A PREFABRICATED FOOT ORTHOTIC. AB - BACKGROUND: Foot orthotics are commonly utilized in the treatment of patellofemoral pain (PFP) and have shown clinical benefit; however, their mechanism of action remains unclear. Patellofemoral joint stress (PFJS) is thought to be one of the main etiological factors associated with PFP. HYPOTHESIS/PURPOSE: The primary purpose of this study was to investigate the effects of a prefabricated foot orthotic with 5 degrees of medial rearfoot wedging on the magnitude and the timing of the peak PFJS in a group of healthy female recreational athletes. The hypothesis was that there would be significant reduction in the peak patellofemoral joint stress and a delay in the timing of this peak in the orthotic condition. STUDY DESIGN: Cross-sectional. METHODS: Kinematic and kinetic data were collected during running trials in a group of healthy, female recreational athletes. The knee angle and moment data in the sagittal plane were incorporated into a previously developed model to estimate patellofemoral joint stress. The dependent variables of interest were the peak patellofemoral joint stress as well as the percentage of stance at which this peak occurred, as both the magnitude and the timing of the joint loading are thought to be important in overuse running injuries. RESULTS: The peak patellofemoral joint stress significantly increased in the orthotic condition by 5.8% (p=.02, ES=0.24), which does not support the initial hypothesis. However, the orthotic did significantly delay the timing of the peak during the stance phase by 3.8% (p=.002, ES=0.47). CONCLUSIONS: The finding that the peak patellofemoral joint stress increased in the orthotic condition did not support the initial hypothesis. However, the finding that the timing of this peak was delayed to later in the stance phase in the orthotic condition did support the initial hypothesis and may be related to the clinical improvements previously reported in subjects with PFP. LEVEL OF EVIDENCE: Level 4. PMID- 26673988 TI - Oral steroid contraception. AB - Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed. PMID- 26673989 TI - Models for projecting supply and demand for nurses in Israel. AB - BACKGROUND: Concern is growing over serious shortages in the nursing workforce and imbalance between supply and demand. Projections indicate that the demand for the nursing workforce will increase due to the aging population and an increase of the percentage of elderly people requiring assistance. STUDY GOALS: To examine the expected balance between supply and several demand projections for nurses in Israel in order to contribute to planning the nursing workforce. METHODS: 1. Open interviews with key figures in the healthcare and nursing care systems; 2. Examination of supply and demand for nurses; 3. Examination of the balance between supply and demand projections. MAIN FINDINGS: A considerable gap was found between the supply and demand projections for registered nurses, which will increase over time according to each of the demand projection models up to 2030. All of the models indicate that the projected shortage will be significantly affected by the age at which the nurses retire. Models based on a fixed ratio of nurses or infrastructure (beds, positions) per population show a particularly great gap between demand and supply. However, a more conservative model (based on hospital utilization), that takes the system's infrastructures and limitations, as well as the growing population and changes in its composition into account, without an increase in the direct ratio of the number of nurses, also predict a significant shortage of nurses within 20 years. CONCLUSIONS: The gaps between the demand and supply projections indicate the need to augment the workforce in addition to the steps currently taken to recruit nursing staff and increase the number of training institutions for nurses. The relatively simple supply prediction models, which are based on available sources of information that can be easily revised, will make it possible to monitor and update projections regularly over time. The models developed in this study should help the process of long-term strategic planning for the number of nurses in Israel. PMID- 26673990 TI - [Triple Negative Breast Cancer]. AB - BACKGROUND: In the Czech Republic, around 6,500 women get breast cancer each year; out of this number, nearly 1,000 women are triple negative subtype. Triple negative breast cancer is characterized by lack of expression of alpha-estrogen, progesterone, and HER2 receptors. Vast majority of these cases are low differentiated carcinomas, majority belonging to the basal-like subgroup defined originally by DNA chips. Clinically, they are characterized by greater aggressiveness, frequent rate of local recurrence and organ metastases. They are more common in younger women and are associated with the occurrence of hereditary forms of breast cancer caused by pathogenic mutations in the BRCA1 gene and in rare cases also BRCA2. AIM: The objective of this review is to provide comprehensive information about current knowledge of triple negative breast cancer. This paper summarizes information about epidemiology and etiopathogenesis of this disease, describes risk factors for both sporadic and hereditary forms of triple negative breast cancer, addresses histopathologic and molecular classification of triple negative breast cancer, and these characteristics associates with treatment and prediction of disease development. The article also addresses new anticancer drugs tested for triple negative breast cancer. CONCLUSION: Triple negative breast cancer is a heterogeneous group of diseases with limited therapeutic options. The key to further shift in therapy is detailed knowledge of its clinical and molecular diversity and identification of predictive biomarkers. Further improvement of therapy results of triple negative breast cancer cannot be expected before targeted therapy of this disease is found. PMID- 26673991 TI - [Immunotherapy for the Prevention and Treatment of Breast Cancer]. AB - The immune system is believed to play a dual role in carcinogenesis. On one hand, it could prompt tumorigenesis and cancer progression, on the other hand, it has the capacity to eradicate tumor cells. There has been an evidence of natural immunogenicity in breast cancer and we have also witnessed several attempts to stimulate non-specific antitumor immune response (Coleys toxin, BCG vaccine etc.). New technologies and further knowledge of molecular basis of immune system and its function encouraged the development of effective immunotherapy capable of inducing a solid antitumor activity. These agents appear promissing in the prevention and therapy of breast carcinoma as well. The assumption is based on the results of several antitumor vaccine trials targeted against HER2, MUC1, CEA and mammaglobin-A, as well as immune checkpoint inhibitors (e.g. CTLA-4, PD-1/ PD L1, LAG3). With regards to different mech-anisms of action of these agents, their combination might bring about synergistic antitumor effects. Nonetheless, monoclonal antibodies and cytostatic agents already approved for breast cancer treatment might be exploited for their immunomodulation effect as well. This article addresses prospects for immunotherapy of breast carcinoma in detail. PMID- 26673992 TI - [Psychological Aspects of Intravenous Treatment in Oncology and Permanent Venous Access Devices Tolerance]. AB - BACKGROUND: This paper deals with the psyche of patients during intravenous therapy. Since any intervention in the physical integrity of individuals are necessarily reflected in their mental level, we decided to conduct a survey dealing with tolerance of intravenous therapy in cancer patients. Especially, we focused on long-term venous access devices tolerance. PATIENTS AND METHODS: The aim of this study was to evaluate descriptively patients' awareness of the administration of parenteral drugs, risks in the application and the differences between the administration of drugs to the central and peripheral venous system. To collect data, own questionnaire containing 21 questions was compiled. It was distributed to patients in the oncology department and outpatient oncology ward at the hospital Novy Jicin. Patients signed an informed consent for data collection. One hundred valid questionnaires were evaluated in the analysis of the data. RESULTS: The results of the study generally indicate that patients do not tolerate venous sampling and intravenous therapy optimally. Patients who have some form of venous access device are mostly satisfied, as it fulfills its mandate of maximum patient comfort. CONCLUSION: The results indicate that most patients know alternatives to peripheral drugs application. However, awareness of this issue is inadequate. The vast majority of patients would recommend the introduction of long-term venous access device to other patients. PMID- 26673993 TI - Thiazolidinediones Regulate the Level of ABC Transporters Expression on Lung Cancer Cells. AB - ATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively efflux various xenobio-tics from the cells across the cell membrane and decrease a drugs efficiency. Lung cancer is the leading cause of death among all types of cancer in the Czech Republic, and its incidence is still rising. Ciglitazone, rosiglitazone and troglitazone belonging to PPARgamma agonist family (formerly used in diabetes mellitus treatment) were selected to investigate their capability to influence expression of ABC transporters on lung cancer cells. Therefore, the effect of PPARgamma of agonists on transcription of following ABC transporters was investigated: multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). We have investigated if these PPARgamma agonists are substrates of ABC transporters using HL60 and HL60 derived cell lines (HL60-MDR1, HL60-MRP1, PLB BCRP) by cytotoxicity test WST-1. We have mapped the changes in mRNA expression level of those transporters in A549 and HEK293 cells after PPARgamma agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPARgamma agonists serve as substrates to at least one ABC transporter under study. PPARgamma activation correlates with up-regulation of PTEN which may modulate the expression of ABC transporters through PI3K/ Akt signaling pathway. We have shown that rosiglitazone and troglitazone inhibit mRNA expression of MDR1 transporter in both cell lines whereas the expression of MRP1 in HEK293 cell was up-regulated after rosiglitazone treatment and the expression of MDR1 was upregulated after ciglitazone treatment. PMID- 26673994 TI - [A Case of Delayed Dia-gnosis of Acral Lentiginous Melanoma]. AB - BACKGROUND: Melanoma is a malignant skin disease. The tumor development is caused by an uncontrollable proliferation of melanocytes. The most common occurrence is on the skin, but melanoma may also develop on the mucous membrane, meninges, and eyes. Some melanomas develop from melanocytic nevus. Acral lentiginous melanoma occurs on palms, feet, fingers and under nails, and is the most common type of melanoma for phototype VI. The most important factor for successful treatment of malignant melanoma is an early detection, excision of the primary tumor and histological staging. Surgical treatment of an early-stage melanoma is a key to successful therapy; however, many patients (mostly men) do not seek medical attention before it istoo late. CASE REPORT: This case study presents a 59-year old patient, who suffers from white coat syndrome and whose finger was amputated for alleged gangrene. Subsequently, brownish black nodules appeared across his arm. Histological examination proved metastases of malignant melanoma. It was only at this phase, when the patient admitted a nevus at the tip of his amputated finger, from which ulceration and gangrene gradually emerged. CONCLUSION: This case demonstrates a combination of multiple unfavorable factors, which led to delayed diagnosis and therapy. PMID- 26673995 TI - [Possible Pitfalls of Ipilimumab Therapy in Malignant Melanoma - a Case Report]. AB - BACKGROUND: Metastatic melanoma is a malignancy with one of the highest mortality rates. However, with the introduction of new drugs during the last decade, the prognosis of patients began to improve. Ipilimumab is one of the first so called modern drugs in melanoma treatment. The therapy is often complicated by adverse effects which are referred as immunerelated adverse events due to its mechanism of action. CASE: We present a case of 68-year- old women with metastatic melanoma who underwent treatment with ipilimumab. The patient encountered several adverse events during the treatment. Some of them are quite common (e.g. skin affections), others (e.g. endocrinopathies) are less frequent. CONCLUSION: This case study highlights the need for close observation not only during the actual treatment with ipilimumab, but also several weeks or months after the last dose. This case study also demonstrates further need of education of doctors who do not usually come in to contact with such patients. PMID- 26673996 TI - Probing Shear Thinning Behaviors of IgG Molecules at the Air-Water Interface via Rheological Methods. AB - Shear thinning behavior, often observed in shear viscosity tests of IgG therapeutic molecules, could lead to significant disparities in the projections for the viscosity profile of a molecule. Despite its importance, molecular determinants of sheer thinning in protein suspensions are largely unknown. To better understand the factors influencing sheer thinning, viscosity profiles of IgG1 and IgG2 molecules were monitored over a wide range of bulk concentrations (0.007-70 mg/mL). The degree of shear-thinning of 70 and 0.007 mg/mL samples was minimal in comparison to the 0.7 mg/mL solution for both IgG molecules. These observations suggest that bulk concentration alone does not determine the degree of sheer thinning, and additional factors play a role. Additional data reveals, within a threshold range of concentrations, that a strong correlation exists between the degree of shear thinning and the surface area to volume (SA:V) ratio of an IgG sample exposed to the interface. The influence of the interface, however, diminishes when the bulk concentration falls outside this concentration window. Also revealed by interfacial oscillatory rheological testing, both IgG molecules showed solid-like behavior (G'i) at the air-water interface at 0.7 mg/mL, whereas liquid-like behavior (G"i) was dominant at 0.007 and 70 mg/mL concentrations. These observations imply that the lack of solid-like behavior was due to the absence of a network structure. Likewise the addition of polysorbate 20 (PS20) to the 0.7 mg/mL solutions decreased the degree of shear thinning by disrupting the network structure at the interface. Taken together, the results presented here suggest that, although shear thinning behavior is a manifestation of an interfacial, rather than a bulk, phenomenon, the extent of it depends on how susceptible the surface molecules are to the air-water interface, where the surface molecular structures are influenced by the bulk properties. PMID- 26673998 TI - Enhancement of oxaliplatin sensitivity in human colorectal cancer by hypericin mediated photodynamic therapy via ROS-related mechanism. AB - The resistance to oxaliplatin (L-OHP) is a major obstacle to ideal therapeutic outcomes in colorectal cancer. Photodynamic therapy (PDT) induces tumor damage through photosensitizer-mediated oxidative cytotoxicity. Hypericin is a well studied photosensitizer. In this study, we explored the role of hypericin mediated PDT (HY-PDT) in sensitizing human colorectal cancer cells towards L-OHP. Pre-treatment with HY-PDT enhanced the anti-tumor activity of L-OHP via decreasing drug efflux and increasing platinum accumulation. Further research showed that HY-PDT-mediated resensitization of resistance cells towards L-OHP was dependent on regulation of MRP-2, instead of p-gp. HY-PDT was also found to inhibit intracellular glutathione (GSH) and Glutathione S-transferase (GST), suggesting the involvement of GSH-related detoxification in the sensitization effect. Additionally, enhanced DNA double-strand breaks (DSBs) was observed following HY-PDT/L-OHP combined treatment. HY-PDT lowered the removing rate of platinum from DNA and down-regulated the expression of ERCC1 and XPF, two critical enzymes involved in nucleotide excision repair (NER) pathway. GSH monoethyl ester (GSH-EE) antagonized HY-PDT-induced ROS and repressed sensitization to platinum. Taken together, HY-PDT mediated sensitization of L-OHP in human colorectal cancer is mediated by ROS, whose mechanism involves affecting drug efflux, GSH-related detoxification and NER-mediated DNA repair. PMID- 26673997 TI - Relation of Paraoxonase1, Arylesterase and Lipid Profile in Ischemic Stroke Patients. AB - BACKGROUND: Paraoxonase 1 (PON1) is an enzyme associated with High density lipoprotein (HDL) in blood and it is considered to have antioxidant and antiatherogenic properties. PON1 plays an important role in protecting HDL and especially low density lipoprotein (LDL) from oxidative modification by hydrolyzing lipid peroxides which are known to be associated with many vascular diseases including atherosclerosis and ischemic stroke. AIM: The aim of the study was to evaluate and correlate serum paraoxonase (PON1) and arylesterase (ARE) activities as well as lipid profile levels in patients with ischemic stroke. MATERIALS AND METHODS: The study population was comprised of 50 ischemic stroke patients and 50 healthy controls. The serum PON1 and ARE activities were measured spectrophotometrically by using paraoxon and phenylacetate as substrate respectively by Eckerson method. Serum lipid was measured using routine biochemical method. RESULTS: The normality of the distribution of the parameters are assessed by Shapiro-Wilk test. Two sample t-test is applied for hypothesis testing. The serum PONI and arylesterase ARE decreased significantly in ischemic stroke patients (p<0.001). The PON1 was positively correlated with HDL. CONCLUSION: This study strongly suggests that the estimation of HDL-C associated PON1 enzyme gives valuable information for prediction of risk of ischemic stroke due to cerebrovascular thromboembolism. The result shows that PON1 and ARE could be considered as a risk factors for ischemic stroke. PMID- 26674000 TI - Structural and mechanistic insight into substrate binding from the conformational dynamics in apo and substrate-bound DapE enzyme. AB - Conformational dynamics in large biomolecular systems is often associated with their physiological roles. The dynamics of a dimeric microbial enzyme, DapE, with great potential as an antibiotic target, has been studied employing long molecular dynamics simulations of the enzyme in apo form and in substrate bound complex form. The essential dynamics of the apo enzyme and the enzyme-substrate complex are extracted from the principal component analysis of the simulations of these two systems where the first two principal components are analyzed in detail. The essential motion of the enzyme in the substrate bound form exhibits a folding motion of its two catalytic domains over the two dimerization domains, which results in repulsion of water molecules away from the active site of the enzyme-substrate complex. This folding motion also leads to a stabilizing binding free energy of the substrate arising from the favorable interaction of the substrate and side chains of the enzyme. The dynamics in the enzyme-substrate complex results in stronger interaction between the catalytic and dimerization domains reflected by an increased number of inter-domain hydrogen bonds. The substrate, located in the catalytic domain of DapE, establishes contacts with the side chains of the dimerization domain of DapE by extended chains of hydrogen bonds, which emphasizes the role of the dimerization domain in substrate binding. PMID- 26673999 TI - Moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori infection. AB - AIM: To assess the efficacy of moxifloxacin-containing triple therapy after non bismuth quadruple therapy failure for Helicobacter pylori (H. pylori) eradication. METHODS: Between January 2010 and December 2012, we screened individuals who were prescribed non-bismuth quadruple therapy for H. pylori eradication. Among them, a total of 98 patients who failed non-bismuth quadruple therapy received 1-wk or 2-wk moxifloxacin-containing triple therapy (400 mg moxifloxacin once daily, and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated using the (13)C-urea breath test 4 wk later, after treatment completion. The eradication rates were determined by intention-to-treat and per-protocol analyses. RESULTS: In total, 60 and 38 patients received 1-wk and 2-wk moxifloxacin-containing triple therapy, respectively. The intention-to-treat and per-protocol eradication rates were 56.7% (95%CI: 45.0-70.0) and 59.6% (95%CI: 46.6-71.7) in the 1-wk group and 76.3% (95%CI: 63.2-89.5) and 80.6% (95%CI: 66.7-91.9) in the 2-wk group (P = 0.048 and 0.036, respectively). All groups had good compliance (95% vs 94.9%). Neither group showed serious adverse events, and the proportions of patients experiencing mild side effects were not significantly different (21.1% vs 13.9%). Clinical factors such as age, sex, alcohol and smoking habits, comorbidities, and presence of gastric or duodenal ulcer did not influence the eradication therapy efficacy. The efficacy of second-line eradication therapy did not differ significantly according to the first-line regimen. CONCLUSION: Two-week moxifloxacin-containing triple therapy showed better efficacy than a 1-wk regimen after non-bismuth quadruple therapy failure. PMID- 26674002 TI - Trigone ventricular meningiomas: Is it possible to achieve good results even in the absence of high tech tools? AB - BACKGROUND: Intraventricular meningiomas constitute 2% of intracranial meningiomas, representing a challenging disease for neurosurgeons; we report our experience through a case series, emphasizing surgical approaches and results. METHODS: Between 2009 and 2012, four patients underwent microsurgical resection in our department. Clinical and imaging findings, surgical approaches, outcomes, and follow-up were analyzed. RESULTS: Four patients (three females and one male) were included and the signs of intracranial hypertension were the main clinical presentation in all cases. The parietal approach through intraparietal sulcus was performed in 3 cases and parieto-occipital interhemispheric surgical route in 1 case. Gross total resection was achieved in all the patients without additional deficits and without the aid of neuronavigation, intraoperative monitoring, and intraoperative magnetic resonance imaging. CONCLUSION: Gross total resection is the gold standard treatment for such tumors and the intraparietal sulcus approach is an excellent choice for most of the cases. Careful anatomical knowledge contributes to a safer procedure even in the absence of high tech equipment assistance. PMID- 26674001 TI - Differential regional fatty acid distribution in normotensive and preeclampsia placenta. AB - BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFAs) are biologically active fatty acids which regulate placental angiogenesis, inflammation, and oxidative stress. Abnormalities in these aspects have been associated with preeclampsia (PE). Further, placenta has a heterogeneous structure with differential vascularization across different regions. We therefore hypothesize that the distribution of fatty acids in various regions of the placenta is altered in PE leading to poor fetal outcome. METHODS: In this cross-sectional study we recruited 69 normotensive control (NC) and 44 women with PE. PE women were further classified as those delivered preterm (PTPE, n = 24) and at term (TPE, n = 20). Fatty acid levels were analyzed from placental samples from four different regions (CF-central fetal, PF-peripheral fetal, CM-central maternal and PM-peripheral maternal). RESULTS: In the NC placenta, AA levels were lower (p < 0.05) in CM as compared with CF region. However, such differences were not seen in the TPE and PTPE. In contrast, the DHA levels varied between regions only in the PTPE placenta. Between groups, DHA levels were lower (p < 0.05 for both) in the CM and CF regions of the PTPE as compared with NC. The levels of DHA in TPE placenta were similar to NC. AA levels were lower (p < 0.05 for both) in CF region of TPE and PF region of PTPE placenta than NC. CONCLUSIONS: There is differential pattern of LCPUFA distribution across various regions of the NC, TPE and PTPE placenta. This may have implications for placental growth and development as well as transfer of LCPUFA to the fetus. PMID- 26674004 TI - Editorial Comment on: K. Zaniewicz-Kaniewska and I. Sudol-Szopinska Usefulness of sonography in the diagnosis of rheumatoid hand. PMID- 26674003 TI - Metastatic Disease in the Stomach. AB - BACKGROUND: Gastric metastases are rare and represent a late and progressed stage of malignant disease. This review highlights epidemiological, clinical and endoscopic findings as well as therapeutic strategies for metastatic disease of the stomach. SUMMARY: The clinical presentation of gastric metastases is highly unspecific. The endoscopic appearance of gastric metastases is heterogeneous, but the most prevalent findings are solitary and submucosal lesions in the gastric wall. The most prevalent primary tumor spreading to the stomach is breast cancer, followed by renal cell cancer and many others. In general, gastric metastases occur in a late stage of malignant disease and frequently indicate short survival. Specific therapy for gastric metastases does not exist and is mainly performed with chemotherapy according to the primary tumor. Compared with other metastatic diseases, gastric metastases of renal cell cancer and breast cancer need distinct consideration. Gastric metastasis of these cancers presents with a better prognosis, as patients with these conditions can be offered effective chemotherapeutic treatment. KEY MESSAGE: Gastric metastatic disease is a rare clinical presentation. The pathophysiology of gastric metastatic seeding is not well understood. PRACTICAL IMPLICATIONS: In the course of malignant disease the presence of gastric metastases should be taken into account if mucosal or submucosal gastric lesions are present. Therapy in general depends on the primary tumor. PMID- 26674005 TI - Milk as Desensitizing Agent for Treatment of Dentine Hypersensitivity Following Periodontal Treatment Procedures. AB - BACKGROUND: Dentinal hypersensitivity is a commonly observed problem after periodontal treatment procedures in periodontal patients. This further complicates preventive oral hygiene procedures by patients which jeopardize periodontal treatment, or even may aid in periodontal treatment failure. AIMS AND OBJECTIVES: The aims and objectives of present study were to assess the problem of dentine hypersensitivity after non-surgical periodontal treatment and selection of cases for evaluation of commercially available milk at room temperature as mouth rinse for the treatment of dentinal hypersensitivity caused by periodontal treatment. MATERIALS AND METHODS: Patients were selected randomly for nonsurgical periodontal treatment and then were assessed for dentine hypersensitivity. Those having dentine hypersensitivity were assigned in two groups. Group one patients were advised to rinse with commercially available milk at room temperature, group two patients were advised to rinse with luke warm water as control. A four point Verbal Rating Score (VRS) was designed to record the numerical value of dentine hypersensitivity. RESULTS: The results show incidence of 42.5% and prevalence of 77.5% for dentine hypersensitivity after periodontal treatment procedures. After rinsing with milk following periodontal treatment procedures, there was found a significant reduction of dentine hypersensitivity with probability by unpaired t-test as 0.0007 and 0.0001 at tenth and fifteenth day post periodontal treatment procedures respectively. CONCLUSION: This study demonstrated that the milk rinse is a suitable, cheaper, fast acting, home-use and easily available solution to the problem of dentine hypersensitivity after non-surgical periodontal treatment. Milk can be used as desensitizing agent and rinsing with milk for few days is effective in quick reduction of dentine hypersensitivity due to periodontal treatment procedures. PMID- 26674006 TI - Effect of Low CD4 Cell Count on Cervical Squamous Intraepithelial Lesions among HIV-Positive Women in Enugu, Southeastern Nigeria. AB - INTRODUCTION: HIV-positive women are more likely to develop cervical neoplasm. HIV-positive women with low CD4 T-lymphocyte cell count may be more predisposed to cervical squamous intraepithelial lesions (SILs). This study aimed to determine the association between low cellular immunity of HIV positive women, and the prevalence and grade of cervical squamous intraepithelial lesions. MATERIALS AND METHODS: Pap smear was carried out on two cohorts of Highly Active Anti Retroviral Therapy (HAART) experienced HIV-positive women (178 per group) at the AIDS Prevention Initiative in Nigeria-Centre for Disease Control Adult Anti Retroviral clinic of the University of Nigeria Teaching Hospital, Enugu, Nigeria from June to November, 2012. The study group had CD4 cell count of < 200 cells/MUl while the control group had CD4 cell count of >=200 cells/MUl. RESULTS: The mean CD4 cell counts of participants in the study (low CD4) group was 127.9 +/- 47.49 cells/ml while that of the control (high CD4) group was 489.2 +/- 186.36 cells/ml (p < 0.001). The prevalence of SIL was 10.2% (18/176) for the low CD4 group, and 5.7% (10/176) for the high CD4 group [OR = 1.9 (95% CI: 0.85, 4.22)]. The commonest category of SILs identified was Low-grade Squamous Intraepithelial Lesion (LSIL), thus 11 (6.3%) in the study versus 7 (4.0%) in the control group (p = 0.703). CONCLUSION: Prevalence of cervical SILs among HIV positive women on HAART in Enugu, Nigeria is low and has no significant relationship with their CD4 cell count. PMID- 26674008 TI - Stabilisation of carbonyl free amidinato-manganese(II) hydride complexes: "masked" sources of manganese(I) in organometallic synthesis. AB - Reaction of the amidinato-manganese(ii) bromide complex, [{(kappa(2)-N,N' Piso)Mn(MU-Br)}3(THF)2] (Piso = [(DipN)2CBu(t)](-), Dip = 2,6-diisopropylphenyl), with K[BHEt3] affords the first example of a structurally authenticated amidinato manganese(ii) hydride complex, [{(N-,eta(3)-arene-Piso)Mn(MU-H)2}2], via a process which involves a change in the amidinate coordination mode. Treatment of the bulkier precursor complex, [{(Piso'')Mn(MU-Br)}n] (Piso'' = [(Dip''N)2CBu(t)](-), Dip'' = C6H2Pr(i)2(CPh3)-2,6,4), with K[BHEt3] did not lead to an isolable manganese hydride complex, but its reaction with the magnesium(i) complex, [{((Mes)Nacnac)Mg}2] ((Mes)Nacnac = [(MesNCMe)2CH](-), Mes = mesityl), did. This reaction presumably proceeds via a reactive manganese(i) intermediate, which abstracts hydrogen from a reaction component to give [{(kappa(2)-N,N' Piso'')Mn(MU-H)}3]. A comparison of the reactivities of [{(N-,eta(3)-arene Piso)Mn(MU-H)2}2] and the isomorphous manganese(i) complex, [{(N-,eta(3)-arene Piso)Mn}2], toward CO, O2 and N2O was carried out. Reactions with the manganese(i) and manganese(ii) species gave identical results, namely the formation of the manganese(i) carbonyl complex, [(kappa(2)-N,N'-Piso)Mn(CO)4] (reactions with CO), and the manganese(iii)-MU-oxo complex, [{(kappa(2)-N,N' Piso)Mn(MU-O)}2] (reactions with O2 and N2O). These results indicate that [{(N ,eta(3)-arene-Piso)Mn(MU-H)2}2] can act as a "masked" source of an amidinato manganese(i) fragment in synthetic transformations. PMID- 26674007 TI - Mesenchymal stromal cells to modulate immune reconstitution early post hematopoietic cell transplantation. AB - Mesenchymal stromal cells (MSCs) are multipotent progenitor cells known to modulate the immune system and to promote hematopoiesis. These dual effects make MSCs attractive for use as cellular therapy in hematopoietic cell transplantation (HCT). MSCs can be used peri-HCT or pre-engraftment to modulate immune reconstitution, promoting hematopoietic stem cell (HSC) engraftment and/or preventing graft-versus-host disease (GVHD). Pre-clinical studies have demonstrated that MSCs can potentiate HSC engraftment and prevent GVHD in a variety of animal models. Clinical trials have been small and largely non randomized but have established safety and early evidence of efficacy, supporting the need for larger randomized trials. PMID- 26674009 TI - Detection and distribution of ostreid herpesvirus 1 in experimentally infected Pacific oyster spat. AB - High mortality rates are reported in spat and larvae of Pacific oyster Crassostrea gigas and associated with ostreid herpesvirus 1 (OsHV-1) detection in France. Although the viral infection has been experimentally reproduced in oyster larvae and spat, little knowledge is currently available concerning the viral entry and its distribution in organs and tissues. This study compares OsHV-1 DNA and RNA detection and localization in experimentally infected oysters using two virus doses: a low dose that did not induce any mortality and a high dose inducing high mortality. Real time PCR demonstrated significant differences in terms of viral DNA amounts between the two virus doses. RNA transcripts were detected in oysters receiving the highest dose of viral suspension whereas no transcript was observed in oysters injected with the low dose. This study also allowed observing kinetics of viral DNA and RNA detection in different tissues of oyster spat. Finally, viral detection was significantly different in function of tissues (p<0.005), time (p<0.005) with an interaction between tissues and time (p<0.005) for each probe. PMID- 26674010 TI - A novel bacterial infection of the edible crab, Cancer pagurus. AB - There are few reports of bacterial diseases in crabs. A juvenile edible crab (Cancer pagurus) with a rickettsial-like infection was found in the intertidal zone at Freshwater East in South West Wales in July, 2012. Large numbers of bacteria-like particles were found in the haemolymph and within fixed phagocytes of the hepatopancreas. Molecular sequencing and subsequent phylogenetic analysis showed that the infectious agent was a member of the order Rhizobiales and therefore distinct to bacteria classified as rickettsia. PMID- 26674011 TI - Comprehensive Coach Education and Practice Contact Restriction Guidelines Result in Lower Injury Rates in Youth American Football. AB - BACKGROUND: Research evaluating the effect of comprehensive coach education and practice contact restriction in youth football injury rates is sparse. In 2012, USA Football released their Heads Up Football coaching education program (HUF), and Pop Warner Football (PW) instituted guidelines to restrict contact during practice. PURPOSE: To compare injury rates among youth football players aged 5 to 15 years by whether their leagues implemented HUF and/or were PW-affiliated. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Athletic trainers (ATs) evaluated and tracked injuries at each practice and game during the 2014 youth football season. Players were drawn from 10 leagues across 4 states. The non-Heads Up Football (NHUF) group consisted of 704 players (none of whom were PW affiliated) from 29 teams within 4 leagues. The HUF+PW group consisted of 741 players from 27 teams within 2 leagues. The HUF-only group consisted of 663 players from 44 teams within 4 leagues. Injury rates and injury rate ratios (IRRs) were reported with 95% CIs. RESULTS: A total of 370 injuries were reported during 71,262 athlete-exposures (AEs) (rate, 5.19/1000 AEs). Compared with the NHUF group (7.32/1000 AEs), the practice injury rates were lower for the HUF+PW group (0.97/1000 AEs; IRR, 0.13; 95% CI, 0.08-0.21) and the HUF-only group (2.73/1000 AEs; IRR, 0.37; 95% CI, 0.26-0.53). Compared with the NHUF group (13.42/1000 AEs), the game injury rate was lower for the HUF+PW group (3.42/1000 AEs; IRR, 0.25; 95% CI, 0.15-0.44) but not for the HUF-only group (13.76/1000 AEs; IRR, 1.02; 95% CI, 0.73-1.43). Also, the HUF+PW game injury rate was lower than that of HUF-only (IRR, 0.20; 95% CI, 0.12-0.36). Higher injury rates were typically found in those aged 11 to 15 years compared with those aged 5 to 10 years. However, stronger effects related to HUF implementation and PW affiliation were seen among 11- to 15-year-olds. When restricted to concussions only, the sole difference was found between the practice concussion rates among 11- to 15 year-olds in the HUF+PW (0.14/1000 AEs) and NHUF groups (0.79/1000 AEs) (IRR, 0.18; 95% CI, 0.04-0.85). CONCLUSION: These findings support comprehensive coach education and practice contact restrictions as effective methods of injury mitigation. Future research should continue evaluating similar programming within other levels of competition and sports. PMID- 26674012 TI - Expression of mouse CD47 on human cancer cells profoundly increases tumor metastasis in murine models. AB - BACKGROUND: Many commonly used xenograft tumor models do not spontaneously metastasize to distant organs following subcutaneous or orthotopic implantation, limiting their usefulness in preclinical studies. It is generally believed that natural killer cells are the key component of the innate immune system in determining tumor metastatic potential in xenograft models. However, recent studies suggest that macrophages may play an important role, as resident macrophages can eliminate the invading tumor cells if they do not express adequate levels of the CD47 molecule. METHODS: We investigated the effect of overexpressing murine CD47 (mCD47) in PC-3 cells, a commonly used human prostate cancer line, on the metastatic potential in three mouse strains with different genetic background and varying degrees of immunodeficiency. We implanted the tumor cells either subcutaneously or orthotopically and then examined their local and distant metastases. RESULTS: Our results show that mCD47-expressing PC-3 cells subcutaneously implanted in NSG and CB17. Scid mice metastasized to the sentinel lymph node, lung and liver significantly more efficiently than the control cells. When implanted orthotopically to NOD. Scid mice, these cells spontaneously metastasized to lung and liver. CONCLUSIONS: Our data demonstrate that mCD47 can facilitate human tumor cell metastasis in murine models, and that these mCD47-expressing tumor cells may be useful for in vivo studies where spontaneous metastases are desirable. PMID- 26674013 TI - Nuclear Fractal Dimensions as a Tool for Prognostication of Oral Squamous Cell Carcinoma. AB - BACKGROUND: Carcinogenesis follows complex molecular alterations, which are triggered by subtle chromatin architectural changes that are imperceptible to the human eye. As the treatment decisions in Oral Squamous Cell Carcinoma (OSCC) are hindered by the imprecise clinical stage determination and inter-observer variability in histological grading, focus in recent years has shifted to discovering identifiers related to neoplastic cell morphology studied through computer-aided image analysis. One such approach is the assessment of fractal geometry, a technique first described by Mandelbrot, which aids in precise assessment of architecture of natural objects. Assessment and quantification of degree of complexity of these fractal objects (self-similarities in structural complexity at different magnifying scales) is described as fractal dimension (FD). AIM: To evaluate the nuclear fractal dimension (NFD) in OSCC using computer aided image analysis. MATERIALS AND METHODS: Histological sections of 14 selected cases of Oral Squamous Cell Carcinoma (OSCC) and 6 samples of normal buccal mucosa (as control) were stained with Haematoxylin-Eosin and Feulgen stain for histopathological examination and evaluation of nuclear complexity respectively. Fifteen HPF at Invasive Tumour Front (ITF) and Tumour Proper (TP) of Feulgen stained sections were selected and photographed in test and control samples. At ITF, TP and normal buccal mucosa 200 nuclei each were selected and analyzed using Image J software to quantify FD. The test and control groups were compared statistically using Independent sample t-test and One-way ANOVA. RESULTS: Nuclear FD increased progressively towards worst tumour staging as compared to normal buccal mucosa. CONCLUSION: Nuclear FD can be considered for quantification of nuclear architectural changes as a prognostic indicator in OSCC. PMID- 26674014 TI - True Intramural Esophageal Duplication Cyst. AB - Esophageal duplication is the second most common site of gastrointestinal duplication and most cases present with complications. These complications include bleeding, infection, dysphagia, and dyspnea. We report an incidental case of a true intramural esophageal duplication cyst in a new military recruit. The patient was diagnosed in Armed Forces Hospital, Oman. The patient came for a pre recruitment routine check-up, he was found to have a suspicious soft tissue lesion on chest X-ray. He was referred to the thoracic surgeon for further investigations. The investigations included computed tomography and magnetic resonance imaging chest scans, barium swallow, endoscopy and, finally, an endoscopic ultrasound. All workup pointed to a diagnosis of esophageal duplication cyst; therefore, the decision was made to excise the lesion after discussion with the patient about the possible diagnosis and nature of the treatment. The cyst was completely excised thoracoscopically with uneventful recovery. The patient was discharged a few days later and was doing well in subsequent visits to the outpatient department. The histopathological exam confirmed the diagnosis of a true congenital duplication cyst, which was lined by pseudostratified ciliated columnar epithelium overlying double layers of thick bundles of smooth muscle fibers. PMID- 26674015 TI - Prevalence of Hypertension in Boloor Diabetes Study (BDS-II) and its Risk Factors. AB - INTRODUCTION: Hypertension is a major public health problem in India and worldwide. Since hypertension is often asymptomatic, it commonly remains undetected, leading to serious complications if untreated. Hypertension is one of the leading causes of end stage renal disease. It doubles the risk of developing coronary artery disease, increases the risk of congestive heart failure by four folds and that of cerebrovascular disease and stroke by seven folds. Hypertension is directly responsible for 57% of all stroke deaths and 42% of coronary heart disease deaths in India. AIM: To identify prevalence and risk factors for hypertension in a semi urban population of Mangalore, who participated in Boloor Diabetes Study (BDS-II). MATERIALS AND METHODS: This cross-sectional study was conducted on 551 subjects aged >= 20 years who were randomly selected. Hypertension was diagnosed and classified according to Joint National Committee 7 (JNC) criteria. Blood pressure was measured by a doctor using calibrated sphygmomanometer. Anthropometric measurements, lipid and glucose estimations were done for all subjects. Statistical analysis was done using Chi-square test and student's t-test (unpaired). Multivariate logistic regression analysis was done using hypertension as dependent variable and the various risk factors as independent variables. RESULTS: Overall prevalence of hypertension in the community was 41% (227/551) (40.9% in men, 41.3% in women). Prehypertension was found in 40% (223/551) (45.4% in men, 38.1% in women), and only 18.3% (101/551) had normal blood pressure. Stage I hypertension was seen in 29.7% (164/551) (28.9% in men, 30.1% in women). Stage II hypertension was seen in 11.4% (63/551) (12% in men, 11% in women). Age, obesity, diabetes, serum cholesterol and serum triglycerides were strongly associated with hypertension. Only 46% (254/551) of the hypertensive subjects were aware that they were hypertensive. CONCLUSION: Prevalence of hypertension was high in this population. Nearly 54% were unaware of their hypertensive status. Prevalence increased with age, obesity, diabetic status and dyslipidemia. Nearly half of subjects were prehypertensives. This study highlights the need for regular screening coupled with educational programmes to detect, improve awareness and optimally treat hypertension in the community to reduce cardiovascular and renal complications. PMID- 26674016 TI - Stochastic models for the Trojan Y-Chromosome eradication strategy of an invasive species. AB - The Trojan Y-Chromosome (TYC) strategy, an autocidal genetic biocontrol method, has been proposed to eliminate invasive alien species. In this work, we develop a Markov jump process model for this strategy, and we verify that there is a positive probability for wild-type females going extinct within a finite time. Moreover, when sex-reversed Trojan females are introduced at a constant population size, we formulate a stochastic differential equation (SDE) model as an approximation to the proposed Markov jump process model. Using the SDE model, we investigate the probability distribution and expectation of the extinction time of wild-type females by solving Kolmogorov equations associated with these statistics. The results indicate how the probability distribution and expectation of the extinction time are shaped by the initial conditions and the model parameters. PMID- 26674017 TI - Normal and sonographic anatomy of selected peripheral nerves. Part II: Peripheral nerves of the upper limb. AB - The ultrasonographic examination is frequently used for imaging peripheral nerves. It serves to supplement the physical examination, electromyography, and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive, well-tolerated by patients, and relatively inexpensive. Part I of this article series described in detail the characteristic USG picture of peripheral nerves and the proper examination technique, following the example of the median nerve. This nerve is among the most often examined peripheral nerves of the upper limb. This part presents describes the normal anatomy and ultrasound picture of the remaining large nerve branches in the upper extremity and neck - the spinal accessory nerve, the brachial plexus, the suprascapular, axillary, musculocutaneous, radial and ulnar nerves. Their normal anatomy and ultrasonographic appearance have been described, including the division into individual branches. For each of them, specific reference points have been presented, to facilitate the location of the set trunk and its further monitoring. Sites for the application of the ultrasonographic probe at each reference point have been indicated. In the case of the ulnar nerve, the dynamic component of the examination was emphasized. The text is illustrated with images of probe positioning, diagrams of the normal course of the nerves as well as a series of ultrasonographic pictures of normal nerves of the upper limb. This article aims to serve as a guide in the ultrasound examination of the peripheral nerves of the upper extremity. It should be remembered that a thorough knowledge of the area's topographic anatomy is required for this type of examination. PMID- 26674018 TI - Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm. AB - BACKGROUND: Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood. Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF. METHODS: Ligation of the left anterior descending coronary artery (n = 13) or sham operation (n = 11) was performed on Wistar Kyoto rats. After 12 weeks, echocardiography and invasive determination of maximal rates of left ventricular (LV) pressure change were performed. Antioxidative and metabolic enzyme activities and expression of catabolic/anabolic markers were assessed in quadriceps and diaphragm muscle. RESULTS: Ligated rats developed CHF (i.e. severe LV dilatation, reduced LV ejection fraction, and impaired maximal rates of LV pressure change; P < 0.001). There was a divergent response for antioxidant enzymes between the diaphragm and quadriceps in CHF rats, with glutathione peroxidase and manganese superoxide dismutase activity increased in the diaphragm but reduced in the quadriceps relative to shams (P < 0.01). Metabolic enzymes were unaltered in the diaphragm, but cytochrome c oxidase activity (P < 0.01) decreased and lactate dehydrogenase activity (P < 0.05) increased in the quadriceps of CHF animals. Protein expression of the E3 ligase muscle ring finger 1 and proteasome activity were increased (P < 0.05) in both the diaphragm and quadriceps in CHF rats compared with shams. CONCLUSION: Chronic heart failure induced divergent antioxidative and metabolic but similar catabolic responses between the diaphragm and quadriceps. Despite the quadriceps demonstrating significant impairments in CHF, apparent beneficial adaptations of an increased antioxidative capacity were induced in the diaphragm. Nevertheless, muscle ring finger 1 and proteasome activity (markers of protein degradation) were elevated and oxidative enzyme activity failed to increase in the diaphragm of CHF rats, which suggest that a myopathy is likely present in respiratory muscle in CHF, despite its constant activation. PMID- 26674019 TI - Plant species forbidden in health food and their toxic constituents, toxicology and detoxification. AB - Many plants with pharmacological efficacies are widely used as ingredients in so called "health foods", but many of them are toxic. In order to ensure the safety of "health food", the Chinese Ministry of Health has listed 59 materials that are forbidden from being used in health food and are called health food forbidden species (HFFS). This review focuses on 47 plants among the HFFS to discuss research regarding their pharmacology, toxicology, and detoxification methods. According to the literature published in the last 2 decades, the main constituents and the pharmacology of such plants are described here, especially their toxic constituents and toxicology. The toxicity mechanisms of several typical toxic components from the 47 plants are outlined and some effective detoxification methods are introduced. Although all HFFS are poisonous, they are considered to be useful in the treatment of many diseases. How to keep their pharmacological effects and at the same time decrease their toxicity is a great challenge. In the future, more attention should be paid to the application of modern science and technology in the exploration of the toxicology and detoxification of HFFS. PMID- 26674020 TI - Resistance Potential of Bread Wheat Genotypes Against Yellow Rust Disease Under Egyptian Climate. AB - Yellow rust (stripe rust), caused by Puccinia striiformis f. sp. tritici, is one of the most destructive foliar diseases of wheat in Egypt and worldwide. In order to identify wheat genotypes resistant to yellow rust and develop molecular markers associated with the resistance, fifty F8 recombinant inbred lines (RILs) derived from a cross between resistant and susceptible bread wheat landraces were obtained. Artificial infection of Puccinia striiformis was performed under greenhouse conditions during two growing seasons and relative resistance index (RRI) was calculated. Two Egyptian bread wheat cultivars i.e. Giza-168 (resistant) and Sakha-69 (susceptible) were also evaluated. RRI values of two year trial showed that 10 RILs responded with RRI value >6 <9 with an average of 7.29, which exceeded the Egyptian bread wheat cultivar Giza-168 (5.58). Thirty three RILs were included among the acceptable range having RRI value >2 <6. However, only 7 RILs showed RRI value <2. Five RILs expressed hypersensitive type of resistance (R) against the pathogen and showed the lowest Average Coefficient of Infection (ACI). Bulked segregant analysis (BSA) with eight simple sequence repeat (SSR), eight sequence-related amplified polymorphism (SRAP) and sixteen random amplified polymorphic DNA (RAPD) markers revealed that three SSR, three SRAP and six RAPD markers were found to be associated with the resistance to yellow rust. However, further molecular analyses would be performed to confirm markers associated with the resistance and suitable for marker-assisted selection. Resistant RILs identified in the study could be efficiently used to improve the resistance to yellow rust in wheat. PMID- 26674021 TI - It's only mental. PMID- 26674022 TI - [Refugees, asylum seekers and us]. PMID- 26674023 TI - [Critical pathways for mental disorders?]. PMID- 26674025 TI - [M. Bretthauer & E. Hem reply]. PMID- 26674024 TI - [Re: Circumcision of boys]. PMID- 26674026 TI - [Re: The practice consultant scheme at a crossroads]. PMID- 26674027 TI - [Lung cancer-changes in incidence by gender, age and county of residence 1984 2013]. PMID- 26674028 TI - [Drugs for smoking cessation on blue prescription?]. PMID- 26674029 TI - [E-cigarettes--an important measure against damages from smoking]. PMID- 26674030 TI - MSIS celebrates 40 years. PMID- 26674031 TI - Creating the interprofessional health team of the future. PMID- 26674032 TI - [Large blood clots in the brain should be removed with thrombectomy]. PMID- 26674033 TI - [Not Available]. PMID- 26674034 TI - [Not Available]. PMID- 26674035 TI - Seasonally adjusted birth frequencies follow the Poisson distribution. AB - BACKGROUND: Variations in birth frequencies have an impact on activity planning in maternity wards. Previous studies of this phenomenon have commonly included elective births. A Danish study of spontaneous births found that birth frequencies were well modelled by a Poisson process. Somewhat unexpectedly, there were also weekly variations in the frequency of spontaneous births. Another study claimed that birth frequencies follow the Benford distribution. Our objective was to test these results. MATERIAL AND METHOD: We analysed 50,017 spontaneous births at Akershus University Hospital in the period 1999-2014. To investigate the Poisson distribution of these births, we plotted their variance over a sliding average. We specified various Poisson regression models, with the number of births on a given day as the outcome variable. The explanatory variables included various combinations of years, months, days of the week and the digit sum of the date. RESULTS: The relationship between the variance and the average fits well with an underlying Poisson process. A Benford distribution was disproved by a goodness-of-fit test (p < 0.01). The fundamental model with year and month as explanatory variables is significantly improved (p < 0.001) by adding day of the week as an explanatory variable. Altogether 7.5% more children are born on Tuesdays than on Sundays. The digit sum of the date is non-significant as an explanatory variable (p = 0.23), nor does it increase the explained variance. INERPRETATION: Spontaneous births are well modelled by a time-dependent Poisson process when monthly and day-of-the-week variation is included. The frequency is highest in summer towards June and July, Friday and Tuesday stand out as particularly busy days, and the activity level is at its lowest during weekends. PMID- 26674037 TI - A forgettable Christmas purchase. PMID- 26674038 TI - [Giant cell arteritis]. PMID- 26674036 TI - Tuberculosis outbreak in Eastern Norway. AB - BACKGROUND: Tuberculosis is a rare disease in Norway, especially among those who are born here. Contact tracing for cases of pulmonary tuberculosis is essential to find others who are ill or infected, and to prevent further infection. This article describes the investigation of an outbreak in which many of those infected or ill were Norwegian adolescents. MATERIAL AND METHOD: Nine persons directly or indirectly associated with the same educational institution were diagnosed with tuberculosis in 2013. Genetic testing of tuberculosis bacteria linked a further 13 cases of the disease reported in Eastern Norway during the period 2009-2013 to the outbreak. Information from the Norwegian Surveillance System for Communicable Diseases (MSIS) was used to investigate the outbreak, and information was also retrieved on exposure and contact networks. RESULTS: The first patient at the educational institution had long-term symptoms before diagnosis. Contact tracing for this case included 319 persons, of whom eight were ill, 49 infected and 37 received preventive therapy. The extent of contract tracing for the remaining 21 cases varied and included a total of 313 persons, of whom two were found to be ill (included in the 21 cases), 30 were infected and 12 received preventive therapy. INTERPRETATION: Delayed diagnosis led to an unusually large tuberculosis outbreak in a Norwegian context. The extent of contact tracing varied with no obvious relation to the infectiousness of the index patient. The outbreak demonstrates the importance of continued vigilance with regard to tuberculosis as a differential diagnosis, also among patients born in Norway. PMID- 26674040 TI - Chronic fatigue syndrome/myalgic encephalo-myelitis--pathophysiology, diagnosis and treatment. PMID- 26674039 TI - [A 14-day-old boy with jaundice and apnoea]. AB - We describe an infant who was readmitted from home at 14 days of age with jaundice and a history of apnoea and episodes of retrocollis/opisthotonos. He had been only mildly jaundiced on discharge from the maternity clinic at 2 days of age. The total serum bilirubin (TSB) on admission was 542 umol/L, and the infant was treated intensively with triple phototherapy and exchange transfusion. In contrast to what is recommended in Norwegian national guidelines for management of neonatal jaundice, the parents had apparently neither received oral nor written information about jaundice and its follow-up at the time of discharge from maternity. They therefore contacted their child healthcare centre when they had questions about jaundice, though the national guidelines specifically state that follow-up for neonatal jaundice during the first 2 weeks of life is the responsibility of the birth hospital. Inappropriate advice resulted in delayed referral, and the child has been diagnosed with chronic kernicterus, probably the first such case in Norway since national guidelines were formalised in 2006. Genetic work-up disclosed compound heterozygosity for Crigler-Najjar syndrome type I, to the best of our knowledge the first instance of this disorder ever to have been diagnosed in Norway. The incidence of kernicterus is Norway is much lower than in other industrialised countries. This is most likely due to national guidelines for management of neonatal jaundice, which place the responsibility for management and follow-up of jaundice with the birth hospital during the crucial first 2 weeks of life. This case report reminds us that tragedies may occur when guidelines are disregarded. PMID- 26674042 TI - [Max Losting--Bergen doctor and artist]. PMID- 26674041 TI - Science, numerology and critical sense. PMID- 26674043 TI - [Recovery from a neck shot]. PMID- 26674044 TI - The three first liver transplantations in Norway, and the road leading to them. AB - Although renal transplantation was a therapeutic reality in Norway from 1969, organ transplantation was largely regarded as experimental surgery from its introduction in the early 1950s until the licensing of ciclosporin in 1982. After the first successful renal transplantation in 1954, 13 years elapsed before a liver and a heart were successfully transplanted, both in 1967. Inspired by the pioneers Thomas Starzl in Denver, Colorado, and Roy Yorke Calne in Cambridge, early in 1968 Snorre Aune, Gunnar Schistad and Andreas Skulberg began experimental studies on pigs at Ulleval Hospital to develop a surgical technique for liver transplantation. They collaborated with a team at Rikshospitalet led by Audun Flatmark and performed transplantations there every other week, and every other week at Ulleval. It took over one year of weekly animal experiments before the first transplanted pig survived. The first three transplantations on humans in Norway were performed at Ward 2, Ulleval Hospital in 1969, 1970 and 1972. The first patient died shortly after surgery, the second after 24 days, the third 54 days after transplantation. Snorre Aune, Gunnar Schistad and Andreas Skulberg were awarded the Michael Skielderup gold medal in 1972 for this pioneering work. The article is based on the author's own experience as an assistant surgeon and junior partner in the animal experiments and the first human liver transplantations in Norway, and a survey of relevant publications. PMID- 26674046 TI - [Influenza A/Sydney/5/97]. PMID- 26674045 TI - [Ebola is not Sierra Leone's biggest problem]. PMID- 26674047 TI - [The century of the life sciences?]. PMID- 26674048 TI - [The language column turns 25]. PMID- 26674049 TI - [Not Available]. PMID- 26674051 TI - [Not Available]. PMID- 26674052 TI - [Not Available]. PMID- 26674054 TI - [Not Available]. PMID- 26674053 TI - [Not Available]. PMID- 26674055 TI - [Not Available]. PMID- 26674056 TI - Phenolate based metallomacrocyclic xanthate complexes of Co(II)/Cu(II) and their exclusive deployment in [2 : 2] binuclear N,O-Schiff base macrocycle formation and in vitro anticancer studies. AB - Potassium salts of phenolate based polydentate xanthate ligands 4,4'-bis(2 dithiocarbonatobenzylideneamino)diphenyl ether () and 4,4'-bis(2 dithiocarbonatonaphthylmethylideneamino)diphenyl ether () have been synthesized and characterized, prior to use. The reaction of or with M(OAc)2 in Et3N affords access to a rare series of binuclear metallomacrocyclic xanthate complexes of the type [M2-MU(2)-bis-(kappa(2)S,S-xan(1)/xan(2))] () which quickly forms [2 : 2] binuclear N,O-bidentate Schiff base macrocyclic complexes of the type [M2-MU(2) bis-(kappa(2)N,O-L(1)/L(2))] ( = 4,4'-bis(2-hydroxybenzylideneamino)diphenyl ether, = 4,4'-bis(2-hydroxynaphthylmethylidene-amino)diphenyl ether) via evolution of CS2 in solution. The compounds were characterized by microanalysis, relevant spectroscopy (FT-IR, UV-visible), mass spectrometry (ESI-MS), and powder and single crystal XRD techniques. In vitro anticancer activity of all the compounds was evaluated against HEP 3B (hepatoma) and IMR 32 (neuroblastoma) by the MTT assay. Remarkably, the binuclear copper(ii) xanthate complexes were found to be extremely active against both the cell lines (IC50: 8.1 +/- 0.8 MUM (), 8.8 +/- 1.7 MUM () against HEP 3B and 1.9 +/- 0.3 MUM () and 7.3 +/- 0.6 MUM () against IMR 32) and this projects them as good candidates for potent antitumor agents and the IC50 values confirm their better potency than the reference drug cisplatin. The flow-cytometric density plot illustrates the induction of apoptosis in HEP 3B and IMR 32 cells after treatment with , , , and . PMID- 26674057 TI - Structural alterations in the rat brain and behavioral impairment after status epilepticus: An MRI study. AB - Temporal lobe epilepsy (TLE) is one of the most common neurologic disorders often associated with behavioral impairments and cognitive deficit. Lithium-pilocarpine model of seizures in rodents reproduces many features of human convulsive status epilepticus (SE) and subsequent TLE. In this study, we have investigated changes in the rat brain after lithium-pilocarpine SE using a high-field MRI system for small animals in early and chronic periods after SE. We have studied the relationship between T2 relaxation time measured in these periods and the development of behavioral exploratory response to novelty and habituation in the open field test. A significant increase in T2 in the hippocampus and associated structures was found 2 days after SE and practically resolved by day seven, while an increase in T2 in the parietal and prefrontal cortex appeared 30 days after SE. High T2 values in the parietal cortex and thalamus on day two after SE were associated with an increased mortality risk. A substantial variability in T2 relaxation time was observed in the hippocampus and amygdala 30 days after SE. Rats survived after SE showed locomotor hyperactivity and disruption of long-term habituation in the open field test carried out 5 weeks after the seizures. Interestingly, T2 in the amygdala 30 days after SE had a strong correlation with hyperactivity in the novel open field. Therefore, the amygdala damage may be an important factor in the development of hyperactivity in the chronic period after SE. PMID- 26674058 TI - NMDA and dopamine D1 receptors within NAc-shell regulate IEG proteins expression in reward circuit during cocaine memory reconsolidation. AB - Reactivation of consolidated memory initiates a memory reconsolidation process, during which the reactivated memory is susceptible to strengthening, weakening or updating. Therefore, effective interference with the memory reconsolidation process is expected to be an important treatment for drug addiction. The nucleus accumbens (NAc) has been well recognized as a pathway component that can prevent drug relapse, although the mechanism underlying this function is poorly understood. We aimed to clarify the regulatory role of the NAc in the cocaine memory reconsolidation process, by examining the effect of applying different pharmacological interventions to the NAc on Zif 268 and Fos B expression in the entire reward circuit after cocaine memory reactivation. Through the cocaine induced conditioned place preference (CPP) model, immunohistochemical and immunofluorescence staining for Zif 268 and Fos B were used to explore the functional activated brain nuclei after cocaine memory reactivation. Our results showed that the expression of Zif 268 and Fos B was commonly increased in the medial prefrontal cortex (mPFC), the infralimbic cortex (IL), the NAc-core, the NAc-shell, the hippocampus (CA1, CA2, and CA3 subregions), the amygdala, the ventral tegmental area (VTA), and the supramammillary nucleus (SuM) following memory reconsolidation, and Zif 268/Fos B co-expression was commonly observed (for Zif 268: 51-68%; for Fos B: 52-66%). Further, bilateral NAc-shell infusion of MK 801 and SCH 23390, but not raclopride or propranolol, prior to addictive memory reconsolidation, decreased Zif 268 and Fos B expression in the entire reward circuit, except for the amygdala, and effectively disturbed subsequent CPP related behavior. In summary, N-methyl-d-aspartate (NMDA) and dopamine D1 receptors, but not dopamine D2 or beta adrenergic receptors, within the NAc shell, may regulate Zif 268 and Fos B expression in most brain nuclei of the reward circuit after cocaine memory reactivation. These findings indicated that the NAc played a key role in regulating addictive memory reconsolidation by influencing the function of the entire addictive memory network. PMID- 26674059 TI - Expert-novice differences in brain function of field hockey players. AB - The aims of this study were to use functional magnetic resonance imaging to examine the neural bases for perceptual-cognitive superiority in a hockey anticipation task. Thirty participants (15 hockey players, 15 non-hockey players) lay in an MRI scanner while performing a video-based task in which they predicted the direction of an oncoming shot in either a hockey or a badminton scenario. Video clips were temporally occluded either 160 ms before the shot was made or 60 ms after the ball/shuttle left the stick/racquet. Behavioral data showed a significant hockey expertise*video-type interaction in which hockey experts were superior to novices with hockey clips but there were no significant differences with badminton clips. The imaging data on the other hand showed a significant main effect of hockey expertise and of video type (hockey vs. badminton), but the expertise*video-type interaction did not survive either a whole-brain or a small volume correction for multiple comparisons. Further analysis of the expertise main effect revealed that when watching hockey clips, experts showed greater activation in the rostral inferior parietal lobule, which has been associated with an action observation network, and greater activation than novices in Brodmann areas 17 and 18 and middle frontal gyrus when watching badminton videos. The results provide partial support both for domain-specific and domain-general expertise effects in an action anticipation task. PMID- 26674060 TI - Thyroid function parameters in normal pregnancies in an iodine sufficient population. AB - BACKGROUND: The aim of this retrospective observational study was to describe thyroid function parameters (fT3, fT4 and TSH) in the course of normal pregnancies. METHODS: Data were obtained between 2006 and 2007 at the University Hospital in Innsbruck, Austria. The starting point was the identification of women who had had a normal birth as recorded in the birth registry of Tyrol. Thyroid function parameters were determined using methods implemented at the Department of Nuclear Medicine in Innsbruck. RESULTS: The fT3 and fT4 values were normally distributed. Grouping the results by trimester revealed the following values: 4.93 +/- 0.59, 4.54 +/- 0.48, and 4.27 +/- 0.45 pmol/l for fT3; and 15.23 +/- 2.43, 13.79 +/- 1.99, and 13.32 +/- 0.2.01 pmol/l for fT4, respectively. The values corresponding to the 10th-percentile were 3.9 pmol/l for fT3 and 11.3 pmol/l for fT4, respectively. TSH values showed a typical left skewed distribution, thus the mean values were calculated after log transformation of the data. The corresponding mean trimestral values for TSH were 1.46 +/- 1.29, 1.68 +/- 1.23, and 1.70 +/- 2.22 mIU/l, respectively. CONCLUSION: In an iodine sufficient population, thyroid function parameters in normal pregnancies do not differ from those in non-pregnant women. Our previously defined reference range for TSH of 0.3 to 3.5 mIU/l is equally valid for normal pregnancies. GENERAL SIGNIFICANCE: The question of cognition and IQ development of children has been proposed to be associated with thyroid function. The addition of data regarding normal thyroid function during pregnancy will contribute to this research. PMID- 26674062 TI - Skip and save: utility of pelvic x-rays in the initial evaluation of blunt trauma patients. AB - BACKGROUND: The cost of medical care is an area of major emphasis in the current healthcare environment. Medical providers have a significant role in reducing costs. One way to achieve this goal is to eliminate practices that add little value to patient care. The pelvic x-ray (PXR) obtained during the initial evaluation of blunt trauma may be an example. The objective of this study was to explore the utility of the pelvic x-ray in the initial evaluation of blunt trauma patients. METHODS: Blunt trauma patients with pelvic fractures of any type admitted to our urban trauma center from January 2012 to December 2013 were reviewed. Demographics including age, sex, race, mechanism of injury, and outcomes were collected. Findings on PXR and computed tomography (CT) were compared for correlation. Patients requiring surgery for their pelvic fractures were identified. RESULTS: Of the 3,217 trauma admissions over the 2-year period, 153 patients sustained a pelvic fracture. Mean age was 50 years (15 to 97), male 54%, and Caucasian 46%, Hispanic 31%, African American 22%, and Asian 1%. The average injury severity score was 12.9. The main mechanism of injury was motor vehicle collisions 45%, followed by fall from standing 22% and auto and/or pedestrian accidents 12%. There were 22 patients that did not have both CT and pelvic imaging for comparison. Of the 131 patients with both CT and pelvic films, findings were the same in 43 (33%). CT identified one or more additional pelvic fractures in 88 (67%) patients compared with the PXR. In 29 patients (22%), pelvic fractures were not evident on PXR with fractures only identified by CT. The most common missed fractures on PXR were sacral and iliac injuries. Of the 153 patients with pelvic fractures, 24% required surgery for their pelvic injuries. Mortality was 4% for nonpelvic fracture-related causes. The PXR findings did not change management provided by trauma team in the emergency department. CONCLUSIONS: As expected, CT is more sensitive in identifying pelvic fractures compared with PXR. Most blunt trauma patients are undergoing further evaluation with CT. We therefore propose that in patients that are normotensive with no pelvic instability or hip dislocation on physical examination who are to undergo further imaging with CT, the pelvic film should be avoided as it adds little value to patient management. The Advanced Trauma Life Support (ATLS) guidelines should be revised to reflect a diminishing role of the PXR in blunt trauma patients. PMID- 26674061 TI - Recurrent skin infection associated with nasal carriage of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus closely related to the EMRSA-15 clone. AB - We report the case of a soldier with recurrent skin infection associated with nasal carriage of a Panton-Valentine leukocidin (PVL)-producing methicillin susceptible Staphylococcus aureus (MSSA), closely related to the EMRSA-15 clone. MSSA isolates causing infection not requiring hospitalization usually go unnoticed; however, their typing may be useful to understand the global distribution of successful staphylococcal lineages related to epidemic clones. PVL-positive MSSA strains might serve as reservoirs from which virulent methicillin-resistant strains may evolve and spread. PMID- 26674063 TI - Clinical presentation and outcome of nonfunctional pancreatic neuroendocrine tumors in a modern cohort. AB - BACKGROUND: The natural history of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is largely unstudied due to its rarity. The primary goal of this study was to characterize clinical features and outcomes of incidental NF-PNETs. METHODS: An institutional review board-approved retrospective study of patients with NF-PNET evaluated by the Surgical Oncology of University of Nebraska Medical Center was performed. Patients were evaluated with dedicated pancreatic and liver imaging using multiphasic computed tomographic scan and dedicated magnetic resonance imaging protocols. RESULTS: Forty-six patients (male, 47.8%) were evaluated, and 35 ultimately resected. Of these, 16 tumors were discovered incidentally. The median age was 62 and 59 years in incidental and symptomatically discovered, respectively. Incidental median size was 2.4 cm vs 6 cm in the symptomatic group, with a P value of .037. The presence of lymphatic and liver metastases was 10% and 25% incidental and 45% and 67% for those with symptoms (lymphatic involvement, P = .05; liver metastases P = .07). Median overall survival was 45 and 76 months (P = .03). CONCLUSIONS: Incidentally discovered NF-PNETs represent a malignancy with more questions than answers. Our series indicates that these cancers are more indolent than previously believed. PMID- 26674065 TI - Sonoelastographic evaluation with the determination of compressibility ratio for symmetrical prostatic regions in the diagnosis of clinically significant prostate cancer. AB - AIM: Sonoelastography is a technique that assesses tissue hardness/compressibility. Utility and sensitivity of the method in prostate cancer diagnostics were assessed compared to the current gold standard in prostate cancer diagnostics i.e. systematic biopsy. MATERIAL AND METHODS: The study involved 84 patients suspected of prostate cancer based on elevated PSA levels or abnormal per rectal examination findings. Sonoelastography was used to evaluate the prostate gland. In the case of regions with hardness two-fold greater than that of symmetric prostate area (strain ratio >2), targeted biopsy was used; which was followed by an ultrasound-guided 8- or 10-core systematic biopsy (regardless of sonoelastography-indicated sites) as a reference point. RESULTS: The mean age of patients was 69 years. PSA serum levels ranged between 1.02 and 885 ng/dl. The mean prostate volume was 62 ml (19-149 ml). Prostate cancer was found in 39 out of 84 individuals. Statistically significant differences in strain ratios between cancers and benign lesions were shown. Sonoelastography guided biopsy revealed 30 lesions - overall sensitivity 77% (sensitivity of the method - 81%). Sonoelastographic sensitivity increased depending on cancer stage according to the Gleason grading system: 6-60%, 7-75%, 8-83%, 9/10-100%. The estimated sensitivity of systematic biopsy was 92%. CONCLUSIONS: Sonoelastography shows higher diagnostic sensitivity in prostate cancer diagnostics compared to conventional imaging techniques, i.e. grey-scale TRUS, Doppler ultrasound. It allows to reduce the number of collected tissue cores, and thus limit the incidence of complications as well as the costs involved. Sonoelastography using the determination of compressibility ratio for symmetrical prostatic regions may prove useful in the detection of clinically significant prostate cancer. PMID- 26674064 TI - Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis. AB - INTRODUCTION: Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. METHODS: 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. RESULTS: RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF beta levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. CONCLUSION: In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli. PMID- 26674068 TI - [Ru(phen)2dppz](2+) luminescence reveals nanoscale variation of polarity in the cyclodextrin cavity. AB - Phosphorylation of beta-cyclodextrin enhances binding with Ru(II)polypyridyl complexes, and promotes selectivity based on chirality and ligand hydrophobicity. For [Ru(phen)2dppz](2+), inclusion of dppz results in a dramatic increase in luminescence with multiple lifetimes. The sensitive response of photophysics to the environment reveals nanoscale variation of polarity. PMID- 26674067 TI - The construct validity of the Dutch version of the activity card sort. AB - PURPOSE: Establishing construct validity of the ACS-NL in individuals with Parkinson's disease (PD). METHOD: Discriminative validity was established in 191 community-dwelling individuals with PD using an extreme groups design (Hoehn and Yahr stages 1 and 3). Convergent validity was determined by relating the performance scores of the ACS-NL to the scores of the Canadian Occupational Performance Measure (COPM) and the Parkinson's Disease Questionnaire (PDQ-39) scores, and relating ACS-NL satisfaction scores to the COPM scores and to the Utrecht Scale for Evaluation of Rehabilitation Participation (USER-P). RESULTS: The ACS-NL discriminated between individuals with PD with H&Y stages 1 and 3 (U = 524.5, Z = -5.453). ACS-NL performance scores correlated weakly with COPM scores (r = (0).19) and moderately with PDQ-39 scores (r = 0.44-0.55). The ACS-NL satisfaction scores correlated weakly with COPM scores (r = 0.23), and moderately with USER-P scores (r >= 0.40). CONCLUSIONS: This study contributed to the validation of the ACS-NL. The assessment enhances the possibility of monitoring participation in activities in individuals with PD. Implications for Rehabilitation The ACS-NL appears to hold good potential for use in the assessment of participation in activities in individuals with PD. The ACS-NL has added value parallel to administration of other instruments measuring participation (COPM) and quality of life (PDQ-39). This study demonstrates the capacity of the ACS to measure a unique construct of participation and helps to improve the psychometric properties and administration of the ACS-NL in practice. PMID- 26674066 TI - Low Doses of Camptothecin Induced Hormetic and Neuroprotective Effects in PC12 Cells. AB - Hormetic response is an adaptive mechanism for a cell or organism surviving in an unfavorable environment. It has been an intriguing subject of researches covering a broad range of biological and medical disciplines, in which the underlying significance and molecular mechanisms are under intensive investigation. In the present study, we demonstrated that topoisomerase I inhibitor camptothecin (CPT), a potent anticancer agent, induced an obvious hormetic response in rat pheochromocytoma PC12 cells. Camptothecin inhibited PC12 cell growth at relative high doses as generally acknowledged while stimulated the cell growth by as much as 39% at low doses. Moreover, low doses of CPT protected the cells from hydrogen peroxide (H2O2)-induced cell death. Phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were reported playing pivotal roles in protecting cells from oxidative stress. We observed that these 2 pathways were upregulated by low doses of CPT, as evidenced by increased levels of phosphorylated PI3K, phosphorylated Akt, phosphorylated mammalian target of rapamycin, Nrf2, and HO-1; and abolishment of the growth promoting and neuroprotective effects of CPT by LY294002, a PI3K inhibitor. These results suggest that the hormetic and neuroprotective effects of CPT at low doses on PC12 cells were attributable, at least partially, to upregulated PI3K/Akt and Nrf2/HO-1 pathways. PMID- 26674069 TI - Is There a Preventive Role for Vernix Caseosa?: An Invitro Study. AB - BACKGROUND: Vernix caseosa is a naturally occurring substance covering the skin of the newborn babies. Chemical composition of Vernix caseosa has been studied. But the antibacterial properties have not been explored phenotypically. There has been only a few studies related to the properties of Vernix caseosa (VC) and most of them focused on deciphering the chemical nature of VC. These studies found that VC has enzymes such as lysozyme, cathelicidin, lactoferrin, defencins, etc, but no study has proved their presence phenotypically. AIM: To know the anti bacterial and mechanical barrier properties of VC. MATERIALS AND METHODS: A cross sectional study done at Government Lady Goshen Hospital, Mangalore, India. Subjects- 63 healthy infants born by LSCS (Lower Segment Caesaren Section) (Confidence interval- 95%, Power- 90%). In lab, sterility of Vernix caseosa was determined. Lawn culture of S.aureus and E.coli on nutrient agar was done and wells were made in it. Vernix broth was prepared using Tween 80 and was put into the well. It was incubated overnight at 37 degrees C and observed for area of Decreased Bacterial Growth (DBG) around the well. Filter papers impregnated with VC were used for testing for mechanical barrier properties. STATISTICAL ANALYSIS: Data was entered in SPSS 12.0 version and analysed. The zone of inhibition (in mm) in case of bacterial growth was expressed as mean with standard deviation. Student's independent t-test was used to compare the means across the groups (males and females). RESULTS: There was no significant difference in the anti bacterial property based on gender. DBG {mean (SD)} for E.coli and S.aureus was 18.06 mm (1.56) and 13.34 mm (1.94) respectively (p-value <0.000). Result for mechanical barrier was inconclusive due to limitations explained in the article. CONCLUSION: Vernix caseosa has antibacterial properties. But further studies are needed to explore the mechanical barrier properties against bacteria. PMID- 26674071 TI - Nanoindentation of Isometric Viruses on Deterministically Corrugated Substrates. AB - It has been just over 100 years since inventor Joseph Coyle perfected the egg carton-a package format that has known very little changes since its first appearance ( Dhillon , S. B. C. Inventor Created Better Way to Carry Eggs. In The Globe and Mail Vancouver , 2013 ). In this article, we extend Coyle's old idea to the study of mechanical properties of viruses. Virus stiffness, strength, and breaking force obtained by force spectroscopy atomic force microscopy (AFM) provide the knowledge required for designing nanocontainers for applications in biotechnology and medicine, and for understanding the fundamentals of virus-host interaction such as virus translocation from one cellular compartment to another. In previous studies, virus particles adsorbed on flat surfaces from a physiological buffer were subjected to directional deformation by a known force exerted via a microscopic probe. The affinity between the virus shell and surface is required to be strong enough to anchor particles on the substrate while they are indented or imaged, yet sufficiently weak to preserve the native structure and interactions prior deformation. The specific question addressed here is whether an experimental scheme characterized by increased contact area and stable mechanical equilibrium under directional compression would provide a more reliable characterization than the traditional flat substrate approach. PMID- 26674072 TI - Clozapine induced pancytopenia leading to severe sepsis: an unusual early complication. AB - BACKGROUND: Clozapine is a second generation antipsychotic used to treat resistant schizophrenia and other psychotic illnesses. Leucopenia or agranulocytosis is a rare side effect of this drug. Pancytopenia is an extremely rare side effect of clozapine and literature review showed only one such case in where the pancytopenia developed several months after starting clozapine together with other antipsychotic drugs. CASE PRESENTATION: A 26-year-old Sri Lankan male was admitted with fever for 3 days. Apart from generalized body aches there were no other significant symptoms. His blood counts showed pancytopenia. He was being treated for a resistant schizophrenia and clozapine was started only 4 weeks before. Common causes for pancytopenia were excluded, and a diagnosis of clozapine induced pancytopenia was made. He was managed in the intensive care unit with broad spectrum antibiotics, antifungals and granulocyte colony stimulating factors. He made a complete recovery after 4 weeks. CONCLUSION: This is a rare and probably the first reported case of early onset clozapine induced pancytopenia complicated by severe sepsis recovering completely. PMID- 26674073 TI - Benefits of Group Foraging Depend on Prey Type in a Small Marine Predator, the Little Penguin. AB - Group foraging provides predators with advantages in over-powering prey larger than themselves or in aggregating small prey for efficient exploitation. For group-living predatory species, cooperative hunting strategies provide inclusive fitness benefits. However, for colonial-breeding predators, the benefit pay-offs of group foraging are less clear due to the potential for intra-specific competition. We used animal-borne cameras to determine the prey types, hunting strategies, and success of little penguins (Eudyptula minor), a small, colonial breeding air-breathing marine predator that has recently been shown to display extensive at-sea foraging associations with conspecifics. Regardless of prey type, little penguins had a higher probability of associating with conspecifics when hunting prey that were aggregated than when prey were solitary. In addition, success was greater when individuals hunted schooling rather than solitary prey. Surprisingly, however, success on schooling prey was similar or greater when individuals hunted on their own than when with conspecifics. These findings suggest individuals may be trading-off the energetic gains of solitary hunting for an increased probability of detecting prey within a spatially and temporally variable prey field by associating with conspecifics. PMID- 26674070 TI - Applications of Multiple Nuclear Genes to the Molecular Phylogeny, Population Genetics and Hybrid Identification in the Mangrove Genus Rhizophora. AB - The genus Rhizophora is one of the most important components of mangrove forests. It is an ideal system for studying biogeography, molecular evolution, population genetics, hybridization and conservation genetics of mangroves. However, there are no sufficient molecular markers to address these topics. Here, we developed 77 pairs of nuclear gene primers, which showed successful PCR amplifications across all five Rhizophora species and sequencing in R. apiculata. Here, we present three tentative applications using a subset of the developed nuclear genes to (I) reconstruct the phylogeny, (II) examine the genetic structure and (III) identify natural hybridization in Rhizophora. Phylogenetic analyses support the hypothesis that Rhizophora had disappeared in the Atlantic-East Pacific (AEP) region and was re-colonized from the IWP region approximately 12.7 Mya. Population genetics analyses in four natural populations of R. apiculata in Hainan, China, revealed extremely low genetic diversity, strong population differentiation and extensive admixture, suggesting that the Pleistocene glaciations, particularly the last glacial maximum, greatly influenced the population dynamics of R. apiculata in Hainan. We also verified the hybrid status of a morphologically intermediate individual between R. apiculata and R. stylosa in Hainan. Based on the sequences of five nuclear genes and one chloroplast intergenic spacer, this individual is likely to be an F1 hybrid, with R. stylosa as its maternal parent. The nuclear gene markers developed in this study should be of great value for characterizing the hybridization and introgression patterns in other cases of this genus and testing the role of natural selection using population genomics approaches. PMID- 26674074 TI - Laterality of Brain Activation for Risk Factors of Addiction. AB - BACKGROUND: Laterality of brain activation is reported for tests of risk factors of addiction- impulsivity and craving-but authors rarely address the potential significance of those asymmetries. OBJECTIVE: The purpose of this study is to demonstrate this laterality and discuss its relevance to cognitive and neurophysiological asymmetries associated with drug abuse vulnerability in order to provide new insights for future research in drug abuse. METHOD: From published reports, brain areas of activation for two tests of response inhibition or craving for drugs of abuse were compiled from fMRI activation peaks and were tabulated for eight sections (octants) in each hemisphere. Percent asymmetries were calculated (R-L/R+L) across studies for each area. RESULTS: For impulsivity, most activation peaks favored the right hemisphere. Overall, the percent difference was 32% (Chi2 = 16.026; p < 0.0001) with the greater asymmetry for anterior peaks (46.8%; Chi(2) = 17.329; p < 0.0001). The asymmetries for cue induced craving were opposite, favoring the left hemisphere by 6.7% (Chi(2) = 4.028; p < 0.05). The consistency of left asymmetry was found for almost all drugs. For nicotine, studies where subjects were not allowed to smoke (deprived) prior to measurement had the same left hemisphere activation but those who smoked (satiated) before the fMRI measure showed right asymmetry. CONCLUSION: Brain activation studies demonstrate different left/right hemispheric contributions for impulsivity versus craving-factors related to addiction. Failure to take laterality into consideration is a missed opportunity in designing studies and gaining insight into the etiology of drug abuse and pathways for treatment. PMID- 26674083 TI - Rapid Emergence and Clonal Dissemination of CTX-M-15-Producing Salmonella enterica Serotype Virchow, South Korea. AB - The prevalence of cefotaxime-resistant Salmonella enterica serotype Virchow has dramatically increased in South Korea since the first isolation in 2011. Of 68 isolates collected over 10 years, 28 cefotaxime-resistant isolates harbored the bla(CTX-M-15) extended-spectrum beta-lactamase gene and were closely related genetically, demonstrating the clonal dissemination of CTX-M-15-producing Salmonella Virchow in South Korea. PMID- 26674085 TI - Correction: Characterization of Chlorinated Aliphatic Hydrocarbons and Environmental Variables in a Shallow Groundwater in Shanghai Using Kriging Interpolation and Multifactorial Analysis. PMID- 26674075 TI - PERK regulated miR-424(322)-503 cluster fine-tunes activation of IRE1 and ATF6 during Unfolded Protein Response. AB - The endoplasmic reticulum (ER) responds to changes in intracellular homeostasis through activation of the unfolded protein response (UPR). UPR can facilitate the restoration of cellular homeostasis, via the concerted activation of three ER stress sensors, namely IRE1, PERK and ATF6. Global approaches in several cellular contexts have revealed that UPR regulates the expression of many miRNAs that play an important role in the regulation of life and death decisions during UPR. Here we show that expression of miR-424(322)-503 cluster is downregulated during UPR. IRE1 inhibitor (4 MU8C) and deficiency of XBP1 had no effect on downregulation of miR-424(322)-503 during UPR. Treatment of cells with CCT030312, a selective activator of EIF2AK3/PERK signalling, leads to the downregulation of miR-424(322) 503 expression. The repression of miR-424(322)-503 cluster during conditions of ER stress is compromised in PERK-deficient MEFs. miR-424 regulates the expression of ATF6 via a miR-424 binding site in its 3' UTR and attenuates the ATF6 transcriptional activity during UPR. Further miR-424 had no effect on IRE1-XBP1 axis but enhanced the regulated IRE1-dependent decay (RIDD). Our results suggest that miR-424 constitutes an obligatory fine-tuning mechanism where PERK-mediated downregulation of miR-424(322)-503 cluster regulates optimal activation of IRE1 and ATF6 during conditions of ER stress. PMID- 26674084 TI - Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice. AB - BACKGROUND: Honokiol is one of the main bioactive constituents of the traditional Chinese herbal drug Magnolia bark (Cortex Magnoliae officinalis, Hou Po). The aim of this study was to probe its anti-type 2 diabetes mellitus effects and the underlying mechanism. METHODS: Type 2 diabetic mouse model was established by intraperitoneally injecting with streptozotocin. Fasting blood glucose, body weight, and lipid profile were measured. The subcutaneous adipose tissue, skeletal muscle, and liver were isolated as well as homogenized. The phospho insulin receptor beta-subunit (IRbeta), IRbeta, phospho-AKT, AKT, phospho-ERK1/2, ERK1/2, phosphotyrosine, and actin were examined by Western blot assay. Cell viability or cytotoxicity was analyzed by using MTT method. The inhibitory potencies of honokiol on the protein tyrosine phosphatase 1B (PTP1B) activity were performed in reaction buffer. Molecular docking and dynamic simulation were also analyzed. RESULTS: In in vivo studies, oral treatment with 200 mg/kg honokiol for 8 weeks significantly decreases the fasting blood glucose in type 2 diabetes mellitus mice. The phosphorylations of the IRbeta and the downstream insulin signaling factors including AKT and ERK1/2 significantly increase in adipose, skeletal muscle, and liver tissue of the honokiol-treated mice. Moreover, honokiol enhanced the insulin-stimulated phosphorylations of IRbeta, AKT, and ERK1/2 in a dose-dependent manner in C2C12 myotube cells. Meanwhile, honokiol enhanced insulin-stimulated GLUT4 translocation. Importantly, honokiol exhibited reversible competitive inhibitory activity against PTP1B with good selectivity in vitro and in vivo. Furthermore, using molecular docking and dynamic simulation approaches, we determined the potential binding mode of honokiol to PTP1B at an atomic level. CONCLUSION: These findings indicated the hypoglycemic effects of honokiol and its mechanism that honokiol improved the insulin sensitivity by targeting PTP1B. Therefore, our study may highlight honokiol as a promising insulin sensitizer for the therapy of type 2 diabetes. PMID- 26674086 TI - Saccharothrix stipae sp. nov., an actinomycete isolated from the rhizosphere of Stipa grandis. AB - An actinomycete, strain D34T, was isolated from a soil sample collected from the rhizosphere of Stipa grandis at Yunwu Mountain in Ningxia, north-west China. Strain D34T showed highest 16S rRNA gene sequence similarity to Saccharothrix espanaensis DSM 44229T (99.0 %), Saccharothrix texasensis NRRL B-16107T (98.7 %) and Saccharothrix variisporea NRRL B-16296T (98.6 %). The strain contained meso diaminopimelic acid, alanine, glycine and glutamic acid as major cell-wall amino acids. Mannose, rhamnose and galactose were the characteristic whole-cell sugars. The fatty acid profile consisted predominantly of iso-C15 : 0, iso-C16 : 0, iso C16 : 1, C17 : 1omega6c, anteiso-C17 : 0 and anteiso-C15 : 0. The phospholipid profile included phosphatidylethanolamine (typical of phospholipid pattern type II). Furthermore, a combination of some physiological and biochemical properties and low DNA-DNA relatedness values indicated that strain D34T was differentiated from members of closely related species. On the basis of these phenotypic, genotypic and chemotaxonomic data, strain D34T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix stipae sp. nov. is proposed. The type strain is D34T ( = JCM 30560T = ACCC19714T). PMID- 26674087 TI - A pilot randomized controlled trial of a self-management group intervention for people with early-stage dementia (The SMART study). AB - BACKGROUND: Self-management equips people to manage the symptoms and lifestyle changes that occur in long-term health conditions; however, there is limited evidence about its effectiveness for people with early-stage dementia. This pilot randomized controlled trial (RCT) explored the feasibility of a self-management intervention for people with early-stage dementia. METHODS: The participants were people with early-stage dementia (n = 24) and for each participant a caregiver also took part. Participants were randomly allocated to either an eight-week self management group intervention or treatment as usual (TAU). Assessments were conducted at baseline, three months and six months post-randomization by a researcher blind to group allocation. The primary outcome measure was self efficacy score at three months. RESULTS: Thirteen people with dementia were randomized to the intervention and 11 to TAU. Two groups were run, the first consisting of six people with dementia and the second of seven people with dementia. There was a small positive effect on self-efficacy with the intervention group showing gains in self-efficacy compared to the TAU group at three months (d = 0.35), and this was maintained at six months (d = 0.23). In terms of intervention acceptability, attrition was minimal, adherence was good, and satisfaction ratings were high. Feedback from participants was analyzed with content analysis. The findings suggest the positive aspects of the intervention were that it fostered independence and reciprocity, promoted social support, offered information, and provided clinician support. CONCLUSIONS: This study has provided preliminary evidence that self-management may be beneficial for people with early-stage dementia. PMID- 26674088 TI - Shifting bottlenecks in acute stroke treatment. PMID- 26674089 TI - Degarelix therapy for prostate cancer in a real-world setting: experience from the German IQUO (Association for Uro-Oncological Quality Assurance) Firmagon(r) registry. AB - BACKGROUND: We investigated the use of the gonadotropin-releasing hormone (GnRH) antagonist degarelix in everyday clinical practice using registry data from uro oncology practices in Germany. METHODS: Data were analysed retrospectively from the IQUO (Association for uro-oncological quality assurance) patient registry. Data were prospectively collected from all consecutive PCa patients treated with degarelix (n = 1010) in 138 uro-oncology practices in Germany between May 2009 and December 2013. RESULTS: Median overall survival had not yet been reached in the all-patient group or in subgroups who had or had not received prior hormonal therapy (HT). Cox regression analysis showed that patients who had received prior HT (n = 542) had a 58 % increased mortality risk (hazard ratio 1.58, 95 % CI 1.20 2.09) versus patients who had not (n = 468) (p = 0.001). Also, in patients who had received prior luteinizing hormone-releasing hormone (LHRH) analogue therapy (LHRH agonists or GnRH antagonists), median time to PSA progression was shorter (209 weeks) than in those who had not received prior LHRH analogues (n = 555; median PSA progression-free survival not yet reached). Degarelix was generally well tolerated. CONCLUSIONS: Degarelix was effective and well tolerated in everyday clinical practice, confirming observations from clinical studies. Patients who received prior HT appeared to have a significantly higher mortality risk. PMID- 26674090 TI - Primary leiomyosarcoma of the submandibular gland: a case report. AB - BACKGROUND: Leiomyosarcoma is a rare malignant mesenchymal tumor that represents 5-7 % of all soft tissue sarcomas. The occurrence of this tumor in the salivary glands is exceptional. Only five cases are reported in the submandibular gland. CASE PRESENTATION: A 65-year-old white Moroccan woman presented with a history of progressive right submandibular swelling which had grown over a period of 8 months. Clinical examination showed a submandibular painless, mobile and hard mass without cervical lymphadenopathy. Ultrasonography and computed tomography revealed a solid and heterogeneous mass measuring 4 * 2 cm involving the submandibular gland. A resection of the gland was performed. Pathological findings were consistent with primary leiomyosarcoma of the submandibular gland. No recurrence occurred after two months of follow-up. CONCLUSION: Primary leiomyosarcoma of the submandibular gland is an extremely rare mesenchymal tumor. Clinical and radiological features are not specific. Differential diagnosis includes metastatic leiomyosarcoma and gastrointestinal stromal tumor, myoepithelioma, sarcomatoid carcinoma, melanoma and other sarcomas. Little is known about the overall biologic behavior of this tumor, but the prognosis seems to be poor. PMID- 26674091 TI - The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini. AB - The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa) experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (<= 20 nN) without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function. PMID- 26674092 TI - Lithium-Sensitive Store-Operated Ca2+ Entry in the Regulation of FGF23 Release. AB - BACKGROUND/AIMS: Lithium, a widely used drug for the treatment of mood disorders, has previously been shown to stimulate the release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)2D3 formation and mineral metabolism. The cellular mechanisms involved have remained elusive. Lithium has been shown to modify Ca2+ signaling. In a wide variety of cells, Ca2+ entry is accomplished by the pore-forming Ca2+ channel subunit Orai1 and its regulator STIM, which stimulates Orai following Ca2+ depletion of intracellular stores. Transcription factors promoting Orai1 expression include NF-kappaB. The present study thus explored whether the effect of lithium on FGF23 involves and requires Ca2+ entry. METHODS: Experiments were performed in UMR106 osteoblastic cells and immortalized primary osteoblasts (IPO). FGF23 and Orai1 transcript levels were estimated from qRT-PCR, cytosolic Ca2+ concentration ([Ca2+]i) from Fura2 fluorescence and store operated Ca2+ entry (SOCE) from an increase in [Ca2+]i following store depletion by inhibition of the sarcoendoplasmatic Ca2+ ATPase (SERCA) with thapsigargin (1 uM). RESULTS: SOCE in UMR106 cells was enhanced by lithium treatment, an effect abrogated by Orai1 inhibitor 2-APB (50 uM). FGF23 transcript levels were increased by lithium and inhibited by Orai1 inhibitors 2-APB (50 uM) and YM58483 (100 nM) as well as NF-kappaB inhibitors wogonin (100 uM) and withaferin A (500 nM). Moreover, Orai1 transcript levels were up-regulated by lithium, an effect attenuated by wogonin and withaferin A. CONCLUSION: Lithium stimulates FGF23 release at least in part by NF-kappaB dependent up-regulation of Orai1 transcription and store operated Ca2+ entry. PMID- 26674093 TI - Editorial. PMID- 26674094 TI - Exercise Plus Metformin in the Fight Against Diabetes. PMID- 26674095 TI - Adipose Tissue Remodeling During Endurance Training. PMID- 26674096 TI - Relapse profile of early breast cancer according to immunohistochemical subtypes: guidance for patient's follow up? AB - PURPOSE: To analyze the profile of annual recurrence rate (ARR) of patients with early breast cancer (BC) in Tunisia. PATIENTS AND METHODS: We classified 293 patients with histologically confirmed early BC relapsing after 1 year of follow up into three subgroups: hormone receptor (HR)+ 'HR' [estrogen receptor (ER)+ or progesterone receptor (PR)+ and human epidermal growth factor receptor 2 (HER2) ], triple negative 'TN' (ER-, PR- and HER2 score 0/1 or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization negative) and HER2 overexpression 'HER2' (HER2+). ARR was restricted to follow-up contribution of each specified time interval. The HR group was the reference group for comparison. RESULTS: A higher proportion of patients who were up to 35 years old (18% versus 10%, p = 0.04), and patients with obesity (46% versus 26%, p = 0.045) was seen in the TN group. Median time to relapse (MTR) was shorter in TN and HER2 groups than in HR patients (20 and 29 months compared with 56 months, respectively, p < 0.001). In the HR group, the ARR was 22%, 16% and 10% at 3, 4 and 5 years respectively, becoming less than 3% at 7 years. In the TN group, 71% of patients relapsed during the first 2 years and the ARR declined rapidly to less than 1.5% after 4 years. In the HER2 group, the ARR peaked at 2 years (29%) and decreased significantly to 7% and 3% at 5 and 7 years respectively. Adjuvant trastuzumab delayed the MTR from 24 to 34 months (p = 0.022). CONCLUSION: The relapse risk in Tunisian patients is higher in young women and patients with HER2+ and TN tumors. A long and close follow up is recommended for patients with HR and HER2. Conversely, we suggest that follow up in patients with TN could be spaced after 4 years (ARR being <1.5% after this period). PMID- 26674098 TI - Wastewater Mediated Activation of Micromotors for Efficient Water Cleaning. AB - We present wastewater-mediated activation of catalytic micromotors for the degradation of nitroaromatic pollutants in water. These next-generation hybrid micromotors are fabricated by growing catalytically active Pd particles over thin metal films (Ti/Fe/Cr), which are then rolled-up into self-propelled tubular microjets. Coupling of catalytically active Pd particles inside the micromotor surface in the presence of a 4-nitrophenol pollutant (with NaBH4 as reductant) results in autonomous motion via the bubble-recoil propulsion mechanism such that the target pollutant mixture (wastewater) is consumed as a fuel, thereby generating nontoxic byproducts. This study also offers several distinct advantages over its predecessors including no pH/temperature manipulation, limited stringent process control and complete destruction of the target pollutant mixture. The improved intermixing ability of the micromotors caused faster degradation ca. 10 times higher as compared to its nonmotile counterpart. The high catalytic efficiency obtained via a wet-lab approach has promising potential in creating hybrid micromotors comprising of multicatalytic systems assembled into one entity for sustainable environmental remediation and theranostics. PMID- 26674099 TI - Assessment of the utility of ultrasonography with high-frequency transducers in the diagnosis of entrapment neuropathies. AB - The primary aim of this paper was to assess the relevance of high-frequency ultra sound examination in qualifying patients for either surgical or conservative treatment of peripheral entrapment neuropathies. The study was conducted in a group of 55 patients aged 7-83 (mean age 43.6), including 28 males and 27 females, who in 2009-2011 were referred to an ultrasound examination due to a clinical suspicion of entrapment neuropathies. For the purposes of the analysis, the patients were divided into four groups: carpal tunnel syndrome (1), ulnar nerve entrapment (2) (cubital tunnel syndrome and Guyon's canal syndrome), posterior interosseous nerve syndrome (3) and other entrapment neuropathies (4). The cases of isolated idiopathic carpal tunnel syndrome were excluded from the analysis. All patients underwent the interview, physical examination and ultrasound examination. Ultrasound examinations were performed with Esaote MyLab 50 and MyLab 60 systems using high-frequency broadband linear transducers: 6-18 MHz. Sixty-seven percent of patients (37 persons) underwent a neurophysiological test. Nerve echostructure, its hyperemia as well as nerve cross-sectional area or, in the case of small nerves, diameter were assessed in all patients. Furthermore, the following were assessed in individual groups: notch sign in group 1, nerve instability in a dynamic ultrasound examination in group 2, nerve angulation in a dynamic ultrasound examination and tenderness on nerve compression at the site of the visualized pathology in group 3. The analyses of the collected material were performed by means of descriptive statistics. The results of clinical and surgical verification were consistent with ultrasound findings in 96.4%. The results indicate that high-frequency ultrasonography is a valuable method in qualifying patients for various types of treatment of peripheral neuropathies resulting from compression. PMID- 26674097 TI - A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients. AB - BACKGROUND: Personalized therapy considering clinical and genetic patient characteristics will further improve breast cancer survival. Two widely used treatments, chemotherapy and radiotherapy, can induce oxidative DNA damage and, if not repaired, cell death. Since base excision repair (BER) activity is specific for oxidative DNA damage, we hypothesized that germline genetic variation in this pathway will affect breast cancer-specific survival depending on treatment. METHODS: We assessed in 1,408 postmenopausal breast cancer patients from the German MARIE study whether cancer specific survival after adjuvant chemotherapy, anthracycline chemotherapy, and radiotherapy is modulated by 127 Single Nucleotide Polymorphisms (SNPs) in 21 BER genes. For SNPs with interaction terms showing p<0.1 (likelihood ratio test) using multivariable Cox proportional hazard analyses, replication in 6,392 patients from nine studies of the Breast Cancer Association Consortium (BCAC) was performed. RESULTS: rs878156 in PARP2 showed a differential effect by chemotherapy (p=0.093) and was replicated in BCAC studies (p=0.009; combined analysis p=0.002). Compared to non-carriers, carriers of the variant G allele (minor allele frequency=0.07) showed better survival after chemotherapy (combined allelic hazard ratio (HR)=0.75, 95% 0.53-1.07) and poorer survival when not treated with chemotherapy (HR=1.42, 95% 1.08-1.85). A similar effect modification by rs878156 was observed for anthracycline-based chemotherapy in both MARIE and BCAC, with improved survival in carriers (combined allelic HR=0.73, 95% CI 0.40-1.32). None of the SNPs showed significant differential effects by radiotherapy. CONCLUSIONS: Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy. These germline SNPs could contribute towards the design of predictive tests for breast cancer patients. PMID- 26674100 TI - Value of ultrasonography in assessment of recent injury of anterior talofibular ligament in children. AB - INTRODUCTION: Sprained ankle is a very common injury in children. Proper treatment of ligament injuries enables full recovery. X-ray and US examinations are commonly available diagnostic methods. MATERIAL AND METHODS: Two hundred and six children (113 girls and 93 boys, mean age 10.6) with recent ankle joint sprain (up to 7 days of injury) were subject to a retrospective analysis. All patients underwent an X-ray and US examination of the ankle joint within 7 days of injury. In 19 patients, anterior talofibular ligament reconstruction was conducted. RESULTS: X-ray failed to visualize a pathology in 129 children (63%); in 24 patients (12%), avulsion fracture of the lateral malleolus was found, and in 36 cases (17%), effusion in the talocrural joint was detected. Ultrasonography failed to visualize a pathology in 19 children (9%); in 60 patients (29%), it showed avulsion fracture of the lateral malleolus involving the attachment of the anterior talofibular ligament (ATFL); in 34 cases (17%), complete ATFL tear was detected, and in 51 patients (25%), partial ATFL injury was found. Other injuries constituted 19%. The surgeries conducted to repair the anterior talofibular ligament (19) confirmed the US/X-ray diagnoses in 100% of cases. Avulsion ATFL injury, i.e. the one that involves the ligament attachment site, is usually found in younger children (median: 8 years of age). Complete ATFL tears (not involving the attachment site) concern older children (median: 14 years of age). CONCLUSIONS: Since X-ray is of limited value in diagnosing ankle joint pathologies in recent sprain injuries in children, soft tissue imaging, i.e. ultrasonography, is the basic examination to assess the ligament complex. Avulsion fractures, which involve the ATFL attachment site and are usually found in younger children, are a consequence of the incomplete ossification and require urgent diagnosis and orthopedic consultation. PMID- 26674101 TI - Ultrasound assessment on selected peripheral nerve pathologies. Part I: Entrapment neuropathies of the upper limb - excluding carpal tunnel syndrome. AB - Ultrasound (US) is one of the methods for imaging entrapment neuropathies, post traumatic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assessment of peripheral nerve trunk pathology - both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrapment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tunnel syndrome, Guyon's canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg's disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonography 2012; 12 (49): 120-163 - Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles). The parameters of ultrasound assessment have been established - echogenicity and echostructure, thickness (edema and related increase in the cross sectional area of the nerve trunk), vascularization and the reciprocal relationship with adjacent tissue. PMID- 26674102 TI - Heart Disease Death Rates in Low Versus High Land Elevation Counties in the U.S. AB - Previous research on land elevation and cancer death rates in the U.S. revealed lower cancer death rates in higher elevations. The present study further tests the possible effect of land elevation on a diffident health outcome, namely, heart disease death rates. U.S. counties not overlapping in their land elevations according to their lowest and highest elevation points were identified. Using an ecological design, heart disease death rates for two races (black and white) corresponding to lower elevation counties were compared to heart disease death rates in higher land elevation counties using the two-sample t-test and effect size statistics. Death rates in higher land elevation counties for both races were lower compared to the death rates in lower land elevation counties (p < 0.001) with large effect sizes (of > 0.70). Since this is an observational study, no causal inference is claimed, and further research is indicated to verify these findings. PMID- 26674104 TI - Hospital trusts need "coherent plan" from government to reduce deficits, says spending watchdog. PMID- 26674103 TI - A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects. AB - Silymarin, a known extract, is used in the treatment of liver diseases with various origins, but its current administration form cannot target the liver because of its poor oral bioavailability. A new type of oral silymarin proliposome aimed at improving silymarin's poor bioavailability and hepatoprotective effects, is introduced in this work. Silymarin-loaded liquid proliposome were prepared using a simple dissolving process. The morphology, particle size, zeta potential, and entrapment efficiency of the silymarin liposomes were analysed. The everted gut sac transport model was used to measure the intestinal transport of liposomes. The liposomal hepatoprotective activity was evaluated in three types of experimental hepatitis animal models. After staining with haematoxylin and eosin, the livers were microscopically examined to analyse any pathological changes. The prepared silymarin proliposome formed silymarin liposomes with a multilayer liposome structure and improved intestinal transport. In an injured liver, the silymarin liposomes produced a stronger hepatoprotective effect through a significant decrease in both the aminotransferase and MDA levels and a significant increase in the SOD and GSH-PX levels compared to orally administered silymarin tablets. This effect was also confirmed histopathologically. In a word, incorporation of silymarin into a liposomal carrier system increased intestinal absorption and showed better hepatoprotective effects compared to silymarin tablets. PMID- 26674105 TI - Configuration-Space Sampling in Potential Energy Surface Fitting: A Space-Reduced Bond-Order Grid Approach. AB - Potential energy surfaces (PESs) for use in dynamics calculations of few-atom reactive systems are commonly modeled as functional forms fitting or interpolating a set of ab initio energies computed at many nuclear configurations. An automated procedure is here proposed for optimal configuration space sampling in generating this set of energies as part of the grid-empowered molecular simulator GEMS (Lagana et al., J. Grid Comput. 2010, 8, 571-586). The scheme is based on a space-reduced formulation of the so-called bond-order variables allowing for a balanced representation of the attractive and repulsive regions of a diatom configuration space. Uniform grids based on space-reduced bond-order variables are proven to outperform those defined on the more conventional bond-length variables in converging the fitted/interpolated PES to the computed ab initio one with increasing number of grid points. Benchmarks are performed on the one- and three-dimensional prototype systems H2 and H3 using both a local-interpolation (modified Shepard) and a global-fitting (Aguado Paniagua) scheme. PMID- 26674106 TI - Effect of localization on the stability of mutualistic ecological networks. AB - The relationships between the core-periphery architecture of the species interaction network and the mechanisms ensuring the stability in mutualistic ecological communities are still unclear. In particular, most studies have focused their attention on asymptotic resilience or persistence, neglecting how perturbations propagate through the system. Here we develop a theoretical framework to evaluate the relationship between the architecture of the interaction networks and the impact of perturbations by studying localization, a measure describing the ability of the perturbation to propagate through the network. We show that mutualistic ecological communities are localized, and localization reduces perturbation propagation and attenuates its impact on species abundance. Localization depends on the topology of the interaction networks, and it positively correlates with the variance of the weighted degree distribution, a signature of the network topological heterogeneity. Our results provide a different perspective on the interplay between the architecture of interaction networks in mutualistic communities and their stability. PMID- 26674107 TI - Intra-abdominal adhesions in ultrasound. Part I: The visceroperitoneal bordeline, anatomy and the method of examination. AB - It needs to be emphasized that ultrasonography is a primary test performed in order to evaluate the abdominal wall and structures located in their vicinity. It allows for the determination of the anatomy and lesions in this localization. Thorough knowledge concerning the ultrasound anatomy of the tested structures constitutes a basis of all diagnostic successes. Therefore, this part of the article is devoted to this subject matter. The possibility to diagnose intra abdominal adhesions with ultrasound is underestimated and rarely used. The aim of this paper is to discuss and document the ultrasound anatomy of the posterior surface of the abdominal wall as well as to present techniques directed at the detection of adhesions, in particular the visceroperitoneal ones. The posterior surface of the abdominal wall constitutes an extensive tissue area of complex structure, with folds and ligaments surrounded by various amounts of the epiperitoneal fat. In some places, this tissue separates the components of the fascia and peritoneum complex. The ultrasound manifestation of this complex is two hyperechogenic lines placed parallelly to each other in the places where they are not separated by the accumulated adipose tissue. Another factor which separates the peritoneum from the viscera is of dynamic character. It is a so called visceral slide induced by easy or deep breathing. Its size should not be lower than 1 cm and the deflections gradually and symmetrically diminish from the epigastric to hypogastric region. Last but not least, the evaluation of the reciprocal relation of the abdominal wall with viscera may be aided by rhythmical manual compressions on the abdominal wall (ballottement sign) performed below the applied ultrasound transducer. During this test, the size of the visceral slide in relation to the abdominal wall is observed. The maneuver is usually performed in uncooperative patients or those with shallow breath. The authors' own experiences indicate that the effectiveness of the test is increased when lower extremities are moderately bent. This relaxes the muscle tension in the anterior wall of the abdomen. To assess the condition of these structures, linear transducers with the frequency of 5-9 MHz prove the most appropriate. In obese patients, a convex transducer with the frequency of 3.5-5 MHz also may be used. The acoustic focus should be set on the borderline of the abdominal wall and viscera and in order to visualize the changes it might be helpful to use harmonic, compound and XRes imaging. When examining the abdominal wall, the cross and longitudinal sections should be made. The complete evaluation of the visceroperitoneal borderline includes nine segments - three in the epigastrium, three in the mid-abdomen and three in the hypogastrium. PMID- 26674108 TI - Atrial Septal Defect with Cyanosis Due To Over-Developed Eustachian Valve Directed Towards Left Atrium: A Very Rare Scenario. AB - Cyanosis in a case of ASD (atrial septal defect) without pulmonary arterial hypertension is quite rare. A patient with ASD and pneumonia is described who had a central cyanosis resulting from the drainage of deoxygenated blood from the inferior vena cava directly into the left atrium through the atrial septal defect due to the presence of an over-developed malpositioned Eustachian valve directed to the left atrium. In conclusion, ASD can present with cyanosis due to an over developed Eustachian valve. PMID- 26674109 TI - Self-Assembly of Parallelly Aligned NiO Hierarchical Nanostructures with Ultrathin Nanosheet Subunits for Electrochemical Supercapacitor Applications. AB - Parallelly aligned NiO hierarchical nanostructures were fabricated using a templated self-assembly method followed by calcinations, where rationally employed pluronic triblock copolymers (P123) are acting as molecular templates for geometrical manipulation of nanocrystals and short-chain alcohols are acting as cosolvents and cosurfactants. Such aligned nanostructure is constructed orderly with several ultrathin two-dimensional (2D) nanosheet subunits with an exceptionally small thickness of only 3 nm in a high degree of orientation and separation. Moreover, the number of assembled nanosheets in a unit can be tuned by changing the concentration of the involving P123. This is the first time to synthesize highly hierarchically ordered and bilaterally symmetrical nanostructures, distributed in diameter of around 200-300 nm, via self-assembly in the liquid phase without solid substrates. The as-synthesized NiO delivered high capacitances of 418 F/g at the current density of 2 A/g with well cycling stability (still maintained 85% after 2000 cycles) and 333 F/g at 10 A/g in rates performance after 60 cycles. These fine electrochemical performances are supposed to be attributed to the hierarchical structures with high specific surface area (SSA, ~164.87 m(2)/g) and ordered multilevel mesopores, which facilitate the electrolyte accessibility and provide more active sites for redox reaction. PMID- 26674110 TI - Colorectal Cancer in Inflammatory Bowel Disease: Epidemiology, Pathogenesis and Surveillance. AB - BACKGROUND: Inflammatory bowel disease (IBD; including ulcerative colitis and Crohn's disease) is associated with an increased risk for colorectal cancer (CRC). Chronic mucosal inflammation is a key factor in the onset of carcinogenesis in IBD patients. Although most gene alterations that cause sporadic CRCs also occur in patients with IBD-associated CRC, some gene sequences and mutation frequencies differ between sporadic CRCs and IBD-associated CRCs. SUMMARY: This review explores the incidence of CRC in IBD patients, with the goal of identifying the risk and protective factors for CRC in order to facilitate dysplasia management via individualized surveillance strategies. KEY MESSAGE: The incidence of CRC is higher among IBD patients. Identifying the risk and protective factors for CRC will facilitate dysplasia management via individualized surveillance strategies. PRACTICAL IMPLICATIONS: Several risk factors, including active inflammation, the coexistence of primary sclerosing cholangitis, a family history of sporadic CRC and the extent and duration of colonic disease, can lead to the development of CRC in patients with IBD. These risk factors should be utilized in individualized surveillance strategies to lower CRC incidence among IBD patients. Use of 5-aminosalicylic acid may play an important role in CRC prevention. Until newer, more reliable markers of IBD associated CRC risk are found, dysplasia will continue to be the best marker of CRC risk in IBD. Dysplasia management continues to play a key role in preventing the progression of carcinogenesis. PMID- 26674111 TI - A phase I study of carfilzomib for relapsed or refractory acute myeloid and acute lymphoblastic leukemia. PMID- 26674112 TI - Leukocyte telomere length and hippocampus volume: a meta-analysis. AB - Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI 0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma. PMID- 26674113 TI - HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene. AB - Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART is gene therapy that targets the CCR5 co-receptor and creates a population of genetically modified host cells that are less susceptible to viral infection. With generic mathematical models we show that gene therapy that only targets the CCR5 co receptor fails to suppress HIV-1 (which is in agreement with current data). We predict that the same gene therapy can be markedly improved if it is combined with a suicide gene that is only expressed upon HIV-1 infection. PMID- 26674114 TI - Identification of functional genes involved in Cd(2+) response of Chinese surf clam (Mactra chinensis) through transcriptome sequencing. AB - The Chinese surf clam Mactra chinensis is an economically important bivalve species in the coastal waters of Liaoning and Shandong Province, China. In this study, we carried out transcriptome sequencing to develop molecular resources for M. chinensis and conducted an acute test of Cd(2+) stimulation through quantitative real-time PCR (qRT-PCR) to analyze the relative expression of six functional genes. A total of 100,839 transcripts and 56,712 unigenes were obtained from 39.9 million filtered reads and 21,305 unigenes were annotated by hitting against NCBI database. According to the results of qRT-PCR, heat shock protein 22 (Hsp22) and cytochrome P450 (CYP450(2C31)) were inhibited in the low concentration, and induced in the high concentration of Cd(2+); thioredoxin peroxidase (TPx-A) was at normal level in low concentration, but induced in high concentration of Cd(2+); glutathione peroxidase A (GPA), glutathione peroxidase 1 (GPA1) and Mn superoxide dismutase gene (MnSOD) were down-regulated when exposed to any treatment groups. Expression levels of the six functional genes following Cd(2+) exposure indicated that these genes were linked to environmental stress. Moreover, the present work enriched the molecule genetic data of M. chinensis. PMID- 26674115 TI - Single and joint ecotoxicity data estimation of organic UV filters and nanomaterials toward selected aquatic organisms. Urban groundwater risk assessment. AB - The hazardous potential of organic UV filters (UV-Fs) is becoming an issue of great concern due to the widespread application of these compounds in most daily use goods, such as hygiene and beauty products. Nanomaterials (NMs) have also been used in personal care products (PCPs) for many years. Nowadays, both classes of chemicals are considered environmental emerging contaminants. Despite some studies performed in vitro and in vivo reported adverse effects of many UV-Fs on the normal development of organisms, there is scarce data regarding acute and chronic toxicity. The aim of the present study was to determine the EC50 values of selected UV-Fs using standardised toxicity assays on three aquatic species i.e. Daphnia magna, Raphidocelis subcapitata and Vibrio fischeri. EC50 values obtained were in the mgl(-1) range for all the species. The estimated toxicity data allowed us to assess the environmental risk posed by selected UV-Fs in urban groundwater from Barcelona (Spain). The calculated ecological risk indicated a negligible impact on the aquifer. Giving the increasing importance of studying mixtures of pollutants and due to the widespread presence of nanomaterials (NMs) in the aquatic environment, other objective of this work was to explore the response on D. magna after exposure to both binary combinations of UV-Fs among them and UV-F with NMs. In all cases but the nano-silver mixtures, joint toxicity was mitigated or even eradicated. PMID- 26674116 TI - Advancing Racial/Ethnic Minority Men's Health Using a Life Course Approach. PMID- 26674117 TI - Intravenous contrast-enhanced sonography in children and adolescents - a single center experience. AB - Compared to adult patients, ultrasonography in children and adolescents is much more common, due to lack of ionizing radiation, and its wide availability. With the introduction of contrast-media for use in ultrasonography, one major drawback of the method could be overcome. In Europe, SonoVue((r)) is the only widely available agent, which due to improved stability makes it possible to image normal and diseased tissue perfusion and vascularization with high accuracy. Inability to hold the breath and voluntary body movement of the patient is less of an obstacle compared to color Doppler techniques and makes the method very attractive for use in children, which, depending on age, may not be very cooperative. Use of intravenous contrast-medium in minors is currently very limited for several reasons: availability, lack of recommendation in national and international guidelines, and lack of official licensing. The article will touch medical indications, technique, safety considerations, and perspective of intravenous use of contrast-media in children and adolescents, including data from a 6-year period in 37 patients. PURPOSE: The purpose of the study was to collect data on ultrasonographic examinations, expanded by intravenous administration of the contrast agent SonoVue((r)) in children and adolescents. Besides assessing diagnostic yield, data on adverse medication effects was collected. MATERIALS AND METHODS: The study includes contrast-enhanced ultrasound examinations in 37 children at a single institution. Indications for the examinations were tumor lesions, infections, traumatic organ injuries, and parenchymal organ ischemia. Parents of the patients and adolescent patients were informed about the off-label use of the contrast agent. Thirty-nine examinations were performed, the average age of the patient was 11.1 years (range 1 to 17 years). RESULTS: All of the examinations yielded additional diagnostic value, always expanding results from B mode and color coded sonography. Overall, most examinations were done to assess the liver (n=16), followed by the kidney in 10 cases. The different etiologies were encountered in the following order: tumor (n=22), infection (n=9), trauma (n=5), ischemia (n=4). Most examinations were performed to evaluate a hepatic lesion (n=12). There was one incident recorded that fit the criteria of a possible adverse effect. In an 8-year-old girl nausea was noted, that started 15 minutes after the end of the examination and resolved spontaneously. In none of the patients medical treatment for adverse effects was necessary. CONCLUSION: Ultrasonography in children, enhanced by intravenous use of contrast medium is feasible and allows for further evaluating cystic and solid tumors, and organ perfusion. Given that proper medical equipment and correct ultrasound machine settings are used, it is a robust method without diagnostic failures. In this small-sized case series there were no severe adverse effects, however, off-label use in children needs to be addressed. PMID- 26674118 TI - IL-8 as mediator in the microenvironment-leukaemia network in acute myeloid leukaemia. AB - The bone marrow microenvironment is physiologically hypoxic with areas being as low as 1% O2, e.g. the stem cell niche. Acute myeloid leukaemia (AML) blasts misuse these bone marrow niches for protection by the local microenvironment, but also might create their own microenvironment. Here we identify IL-8 as a hypoxia regulated cytokine in both AML cell lines and primary AML samples that is induced within 48 hours of severe hypoxia (1% O2). IL-8 lacked effects on AML cells but induced migration in mesenchymal stromal cells (MSC), an integral part of the bone marrow. Accordingly, MSC were significantly increased in AML bone marrow as compared to healthy bone marrow. Interestingly, mononuclear cells obtained from healthy bone marrow displayed both significantly lower endogenous and hypoxia induced production of IL-8. IL-8 mRNA expression in AML blasts from 533 patients differed between genetic subgroups with significantly lower expression of IL-8 in acute promyelocytic leukaemia (APL), while in non APL-AML patients with FLT ITD had the highest IL-8 expression. In this subgroup, high IL-8 expression was also prognostically unfavourable. In conclusion, hypoxia as encountered in the bone marrow specifically increases IL-8 expression of AML, which in turn impacts niche formation. High IL-8 expression might be correlated with poor prognosis in certain AML subsets. PMID- 26674119 TI - Body Size Perceptions among Overweight and Obese African American Women. AB - OBJECTIVE: Understanding body size perceptions and discrepancies among African American women may have implications for effective weight-loss interventions. The purpose of this study is to examine body size perceptions of economically disadvantaged, overweight and obese African American women. DESIGN: Cross sectional using baseline data from a randomized controlled trial. SETTING: 18 census tracts in a central South Carolina city where >= 25% of residents were below poverty income. PARTICIPANTS: 147 economically disadvantaged, overweight and obese African American women. MAIN OUTCOME MEASURES: Using Pulvers' figure rating scale, participants chose the figure: 1) closest to their current figure; 2) they would be satisfied with; and 3) with a body weight that would be a health problem for the average person. Mean body mass indices corresponding to each figure were compared with those in a large sample of White women. RESULTS: Most participants wanted to be smaller (mean=2.6 figures smaller) than their current size. A majority (67%) chose the largest figure as representing a body size that could lead to a health problem, and most (60%) chose a current figure smaller than the figure they believed would be associated with health problems. The mean body mass index for women selecting any given figure as their current size was significantly larger (5.2-10.8 kg/m(2) larger, P<.0001) than those established in the sample of White women. CONCLUSIONS: Although women desired a smaller body size, there nonetheless were misperceptions of body size and the associated health consequences. Body size misperceptions and/or satisfaction may pose barriers for effective weight-loss. PMID- 26674120 TI - ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers. AB - BACKGROUND: Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia mutated and rad3 related (ATR) and DNA-dependent protein kinase catalytic sub-unit (DNA PKcs) play critical roles in DNA damage response (DDR) by linking DNA damage sensing to DDR effectors that regulate cell cycle progression and DNA repair. Our objective was to evaluate if ATM, ATR and DNA-PKcs expressions could predict response to therapy and clinical outcome in epithelial ovarian cancers. METHODS: We investigated ATM, ATR, and DNA-PKcs expressions in ovarian epithelial cancers [protein expression (n = 194 patients), mRNA expression (n = 156 patients)] and correlated to clinicopathological outcomes as well as expression of X-ray repair cross-complementing protein 1 (XRCC1), cell division cycle-45 (CDC45), cyclin dependent kinase 1(CDK1) and Ki-67 in tumours. RESULTS: High ATM protein expression was associated with serous cystadenocarcinomas (p = 0.021) and platinum resistance (p = 0.017). High DNA-PKcs protein expression was associated with serous cystadenocarcinomas (p = 0.006) and advanced stage tumours (p = 0.018). High ATM protein (p = 0.001), high ATM mRNA (p = 0.018), high DNA-PKcs protein (p = 0.002), high DNA-PKcs mRNA (p = 0.044) and high ATR protein (p = 0.001) expressions are correlated with poor ovarian cancer specific survival (OCSS). In multivariate Cox model, high DNA-PKcs (p = 0.006) and high ATR (p = 0.043) protein expressions remain independently associated with poor OCSS. CONCLUSIONS: ATM, ATR and DNA-PKcs expressions may have prognostic and predictive significances in epithelial ovarian cancer. GENERAL SIGNIFICANCE: The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer. PMID- 26674121 TI - Nano-formulation of a photosensitizer using a DNA tetrahedron and its potential for in vivo photodynamic therapy. AB - Photodynamic therapy (PDT) is a cytotoxic treatment using singlet oxygen produced by photosensitizers. Approved porphyrinoid PDT still suffers from a lack of robust production methods and low water solubility. Methylene blue (MB) is a good candidate for the PDT drug, because the dye is an effective photosensitizer, can be easily synthesized, and is already being used in other clinical fields. However, its poor cell/tissue penetration and low stability against the reducible biological conditions should be addressed by using a proper delivery vehicle. Here, we employed a DNA tetrahedron, a self-assembled nanostructure as the carrier for intracellular delivery of MB by taking advantage of the DNA binding property of the photosensitizer and demonstrated photo-induced cytotoxicity by the MB delivered by the DNA nanocarrier. We also evaluated the PDT potency of the MB-loaded DNA nanoconstruct in vivo tumor model to suppress tumor growth. PMID- 26674122 TI - Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline. AB - Cognitive rehabilitation for mild cognitive impairment (MCI) and early Alzheimer's disease is readily available to the geriatric population. Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone. Seventy four adults with subclinical cognitive decline were randomly assigned to computerised cognitive training (CCT), Cognitive Vitality Training (CVT), or an Active Control Group (ACG), and underwent neuropsychological evaluations at baseline and four-month follow-up. Significant differences were found in changes in performance on the Modified Mini Mental State Examination (mMMSE) and measures of verbal learning and memory across treatment groups. Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group, the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory, and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory. There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory. It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone, although both appear superior to more generic forms of cognitive stimulation. PMID- 26674123 TI - The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation. AB - BACKGROUND: UV, including UVA and UVB radiation, is one of the most ubiquitous environmental stress factors to human skin and leads to redox imbalance and, consequently, photoaging and cancer development. The aim of the study was to verify which skin cells, keratinocytes or fibroblasts, were more susceptible to UVA or UVB irradiation. OBJECTIVE: Keratinocytes and fibroblasts were subjected to UVA and UVB irradiation. METHODS: The redox potential (superoxide anion generation and antioxidant level/activity), electrophile level and endocannabinoid system were estimated. RESULTS: The results presented in this paper demonstrate a strong relationship between UV-induced oxidative stress and changes in the endocannabinoid system. Simultaneously, in irradiated cells, the transcription factors Nrf1, Nrf2 and NFkappaB are activated to varying degrees. Fibroblasts have a greater susceptibility to ROS generation and transcription factor activation after both UVA and UVB irradiation than keratinocytes. Keratinocytes are more sensitive to changes in the electrophile levels connected with oxidative stress compared to fibroblasts. CONCLUSION: The differences demonstrated in the response of the tested cells to UV irradiation allow for a better understanding of the mechanisms occurring in the human skin, which may be exploited for future therapies in dermatology. PMID- 26674124 TI - Efficient antigen delivery to the draining lymph nodes is a key component in the immunogenic pathway of the intradermal vaccine. AB - BACKGROUND: It has been clinically demonstrated that intradermal (ID) vaccines have a potential to confer a superior immunogenic profile compared to intramuscular (IM) or subcutaneous (SC) vaccines. In terms of distribution of a vaccine antigen depending on the administration routes, at least two independent immunogenic pathways of the vaccines have been proposed: (1) the antigen recognition by the immune cells present at the vaccine-administered site and (2) the antigen recognition by the lymph node (LN)-resident immune cells through the lymphatic flow from the vaccine-administered site after the antigen is directly delivered into the draining LNs. OBJECTIVE: In order to clarify the key components for the immunogenic pathway of the ID vaccine, the correlation between the kinetics of the antigen distribution to the draining LNs and antibody responses to the antigen were evaluated. METHODS: We compared the antibody responses in the groups with by surgical removal of the administration site immediately after the ID administration, and by surgical removal of the draining LNs before the ID administration. RESULTS: The results suggested that the efficient and direct antigen delivery to the draining LNs plays an important role in the antibody responses to the ID vaccine. Indeed, it was confirmed that the direct administration into the draining LNs with the antigen elicited comparable levels of the antibody responses with the ID vaccine. At the cellular level, it was shown that the LN-resident immune cells such as B cells, dendritic cells, and macrophages including medullary macrophages and subcapsular sinus macrophages interacting with the antigens following the ID administration. Finally, we demonstrated by immunofluorescence analysis that the lymphatic vessels are more diffusely distributed in the dermis as compared with the subcutaneous area and muscle. CONCLUSION: The results of the present study suggested that the skin is an optimal tissue to facilitate the vaccine antigen access to the draining LNs, which is an important immunogenic pathway of the ID vaccine. Further elucidation of regulatory mechanisms underlying such an immunogenic pathway of the ID vaccine would provide us with elements for the development of novel adjuvants and devices to enhance the immunogenicity of the ID vaccines. PMID- 26674125 TI - Addressing gaps in the contraceptive method mix: methods in development. AB - Despite the availability of a variety of contraceptive methods, millions of women still have an unmet need for contraceptive choices. Short-acting methods are plagued by issues with adherence, leading to imperfect or inconsistent use and subsequent unintended pregnancy. Long-acting contraceptive methods such as intrauterine devices and contraceptive implants, while providing highly effective and safe contraception, do not meet the needs of all women, often due to cost, access or acceptability issues. Several new methods are in various stages of development and are designed to address the shortcomings of current methods. Providers should be aware of these future options and how they might better meet women's needs. PMID- 26674126 TI - Emulating avian orographic soaring with a small autonomous glider. AB - This paper explores a method by which an unpowered, fixed-wing micro air vehicle (MAV) may autonomously gain height by utilising orographic updrafts in urban environments. These updrafts are created when wind impinges on both man-made and natural obstacles, and are often highly turbulent and very localised. Thus in contrast to most previous autonomous soaring research, which have focused on large thermals and ridges, we use a technique inspired by kestrels known as 'wind hovering', in order to maintain unpowered flight within small updrafts. A six degree-of-freedom model of a MAV was developed based on wind-tunnel tests and vortex-lattice calculations, and the model was used to develop and test a simple cascaded control system designed to hold the aircraft on a predefined trajectory within an updraft. The wind fields around two typical updraft locations (a building and a hill) were analysed, and a simplified trajectory calculation method was developed by which trajectories for height gain can be calculated on board the aircraft based on a priori knowledge of the wind field. The results of simulations are presented, demonstrating the behaviour of the system in both smooth and turbulent flows. Finally, the results from a series of flight tests are presented. Flight tests at the hill were consistently successful, while flights around the building could not be sustained for periods of more than approximately 20 s. The difficulty of operating near a building is attributable to significant levels of low-frequency unsteadiness (gustiness) in the oncoming wind during the flight tests, effectively resulting in a loss of updraft for sustained periods. PMID- 26674127 TI - Boosting Belligerence: How the July 7, 2005, London Bombings Affected Liberals' Moral Foundations and Prejudice. AB - Major terrorist events, such as the recent attacks in Ankara, Sinai, and Paris, can have profound effects on a nation's values, attitudes, and prejudices. Yet psychological evidence testing the impact of such events via data collected immediately before and after an attack is understandably rare. In the present research, we tested the independent and joint effects of threat (the July 7, 2005, London bombings) and political ideology on endorsement of moral foundations and prejudices among two nationally representative samples (combined N = 2,031) about 6 weeks before and 1 month after the London bombings. After the bombings, there was greater endorsement of the in-group foundation, lower endorsement of the fairness-reciprocity foundation, and stronger prejudices toward Muslims and immigrants. The differences in both the endorsement of the foundations and the prejudices were larger among people with a liberal orientation than among those with a conservative orientation. Furthermore, the changes in endorsement of moral foundations among liberals explained their increases in prejudice. The results highlight the value of psychological theory and research for understanding societal changes in attitudes and prejudices after major terrorist events. PMID- 26674128 TI - The Critical Importance of Retrieval--and Spacing--for Learning. AB - We examined the impact of repeated testing and repeated studying on long-term learning. In Experiment 1, we replicated Karpicke and Roediger's (2008) influential results showing that once information can be recalled, repeated testing on that information enhances learning, whereas restudying that information does not. We then examined whether the apparent ineffectiveness of restudying might be attributable to the spacing differences between items that were inherent in the between-subjects design employed by Karpicke and Roediger. When we controlled for these spacing differences by manipulating the various learning conditions within subjects in Experiment 2, we found that both repeated testing and restudying improved learning, and that learners' awareness of the relative mnemonic benefits of these strategies was enhanced. These findings contribute to understanding how two important factors in learning-test-induced retrieval processes and spacing-can interact, and they illustrate that such interactions can play out differently in between-subjects and within-subjects experimental designs. PMID- 26674129 TI - Beyond Faces and Expertise: Facelike Holistic Processing of Nonface Objects in the Absence of Expertise. AB - Holistic processing-the tendency to perceive objects as indecomposable wholes-has long been viewed as a process specific to faces or objects of expertise. Although current theories differ in what causes holistic processing, they share a fundamental constraint for its generalization: Nonface objects cannot elicit facelike holistic processing in the absence of expertise. Contrary to this prevailing view, here we show that line patterns with salient Gestalt information (i.e., connectedness, closure, and continuity between parts) can be processed as holistically as faces without any training. Moreover, weakening the saliency of Gestalt information in these patterns reduced holistic processing of them, which indicates that Gestalt information plays a crucial role in holistic processing. Therefore, holistic processing can be achieved not only via a top-down route based on expertise, but also via a bottom-up route relying merely on object-based information. The finding that facelike holistic processing can extend beyond the domains of faces and objects of expertise poses a challenge to current dominant theories. PMID- 26674131 TI - The prognostic value of combination of CD90 and OCT4 for hepatocellular carcinoma after curative resection. AB - CD90 has been identified as a candidate marker of cancer stem cells (CSCs) for HCC, whereas it also has been considered as a marker for tumor-associated fibroblasts (CAFs). OCT4, as a key transcription factor required to maintain pluripotency of human embryonic stem cell and cancer cells, has been characterized to be involved in malignant transformation and tumorigenesis of various cancers. This study aimed to examine expression patterns of CD90 in HCC and investigate whether combination of both CD90 and OCT4 could provide a more powerful predictor for prognosis of HCC than either one alone.CD90 and OCT4 were examined by immunohistochemistry. The relationship between CD90/OCT4 expression and clinicopathologic characteristics was analyzed. The correlation between CD90/OCT4 expression and overall survival and disease-free survival was determined with Kaplan-Meier analysis.CD90 was found mainly expressed in tumor associated CAFs and OCT4 was mainly expressed in tumor cells. The expression of CD90 and OCT4 in HCC was significantly higher than in adjacent non-tumor and normal liver tissues. CD90 expression was correlated with pathological grade, satellite lesion, PVTT and recurrence. OCT4 expression was correlated with pathological grade, tumor size and recurrence. Data demonstrated no correlation between CD90 and OCT4. High expression of CD90 or OCT4 predicts a poor prognosis. Furthermore, combination of both CD90 and OCT4 provides a more sensitive predictor for prognosis of HCC than either marker alone.CD90 and OCT4 are both independent and reliable biomarker for predicting prognosis of HCC patients after hepatic resection. Our results indicated the accuracy of prediction can be enhanced by their combination. PMID- 26674130 TI - Critical considerations for developing nucleic acid macromolecule based drug products. AB - Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve. This review provides a synopsis of challenges in the formulation and stability of DNA/m-RNA based medicines and probable mitigation strategies including a brief summary of delivery options to the target cells. Nucleic acid based drugs at various stages of ongoing clinical trials are compiled. PMID- 26674132 TI - Mismatch repair deficiency associated with complete remission to combination programmed cell death ligand immune therapy in a patient with sporadic urothelial carcinoma: immunotheranostic considerations. AB - BACKGROUND: Mismatch repair deficiency (MMRD) is a common pathway of malignant transformation accounting for approximately 15-20 % of human carcinogensis. It has been postulated that MMRD increases tumor antigenicity and highlights a role for immunotherapeutic approach MMR-deficient cancers. This strategy was pursued in a patient with upper tract urothelial carcinoma, and the results are reported here. CASE PRESENTATION: Molecular profiling was performed using next generation DNA sequencing and (IHC) testing for MMR and PD-L1. A patient with sporadic, high grade urothelial carcinoma of the renal pelvis was found to have a hypermutator genotype with 73 mutations occurring amidst 62 known drivers of malignancy, and 340 VUS alterations. MMR deficiency phenotype was confirmed by the absence of MSH2 and MSH6 as well as deleterious mutations in these genes. IHC staining for programmed cell death ligand-1 [PD-L1] revealed 2+ staining in 80 % of cells. The patient gained access to combination immunotherapy trial utilizing MEDI4736 and MEDI0680 through a clinical trial. The patient achieved a prolonged, complete remission within two months and had no severe ill effects from the treatment. CONCLUSION: Given their ability to generate neo-antigens, MMR-deficient cancers may be uniquely susceptible to immune checkpoint inhibitor strategies, including urothelial tract cancers. Screening for MMR deficient cancers has the potential to become a routine strategy for evaluating the role of PD-L1 inhibitors for patient with advanced disease. ( TRIAL REGISTRATION: Clinicaltrials.gov NCT00938834. Registered 13 July 2009). PMID- 26674133 TI - Risks and benefits of compost-like materials prepared by the thermal treatment of raw scallop hepatopancreas for supplying cadmium and the growth of alfalfa (Medicago sativa L.). AB - Scallop hepatopancreas, fishery waste, contains relatively high levels of Cd and organic nitrogen compounds, the latter of which represent a fertilizer. In this study, raw scallop hepatopancreas tissue was thermally treated with sawdust and red loam in the presence of an iron catalyst to produce compost-like materials (CLMs). Two CLM samples were prepared by varying the content of raw scallop hepatopancreas tissue: 46 wt.% for CLM-1 and 18 wt.% for CLM-2. Mixtures of control soil (CTL) and CLMs (CLM content: 10 and 25 wt.%) were examined for the growth of alfalfa (Medicago sativa L.) to evaluate the risks and benefits of using this material for fertilization. The Cd content in shoots and roots of alfalfa, that were grown in the presence of CLMs, was significantly higher than those for the plants grown in the CTL, indicating that Cd had accumulated in the plants from CLMs. The accumulation of Cd in the alfalfa roots was quite high in the case of the 25% CLM-1 sample. However, alfalfa growth was significantly promoted in the presence of 10% CLM-1. This can be attributed to the higher levels of nitrogen and humic substances, which serve as fertilizer components. Although the fertilization effect in case of CLM-1showed a potential benefit, the accumulation of Cd in alfalfa was clearly increased in the presence of both CLMs. In conclusion, the use of CLMs produced from raw scallop hepatopancreas tissue can be considered to have a desirable benefit from standpoint of its use as fertilizer, but is accompanied by a risk of the accumulation of Cd in alfalfa plants. PMID- 26674135 TI - Long term puzzles of the CH and CD energetics and related phenomena revisited; solutions sought through REMPI-photofragmentations of bromomethanes. AB - Ever since the pioneering work by Herzberg and Johns in 1969 (The Astrophysical Journal, 1969, 158, 399) the spectral assignment and the energetics of the fundamental molecular fragment CH, in the region of 63 000-65 000 cm(-1) (7.81 8.06 eV), have remained a puzzle to a large extent. The dissociation of bromoform and deuterated bromoform following two-photon resonance excitations to molecular Rydberg states forms the fragment species CH* and CD* in the excited state A(2)Delta(v' =0) as well as carbon and bromine atoms in the ground and first excited states, C/C* and Br/Br*. Further (1r + 1i)REMPI of CH* and CD* resonance excites the fragments to the energy region of concern, whereas the atom fragments were identified by further (2r + 1i)REMPI. Analysis based on spectral simulations, isotope shifts and comparison with other data allowed spectral identifications, assignments and partial characterization of four highly excited bound states for each of the molecular fragments (CH**/CD**); including the (3)(2)Pi valence state and the (4)(2)Pi Rydberg state, for the first time. Perturbations, shown as line-shifts, line-intensity and/or line-width alterations, due to the level-to-level state interactions between the bound states and predissociations by a repulsive state are recognized. Recording of C(+) signals in REMPI of several bromomethanes for a one-photon energy of about 40 333 cm(-1) allows the clarification of a mystery concerning a broad C(+) band frequently observed. This work, presented, demonstrates the usefulness of molecular REMPI for fragment analysis. PMID- 26674134 TI - Isolation and enrichment of low abundant particles with insulator-based dielectrophoresis. AB - Isolation and enrichment of low-abundant particles are essential steps in many bio-analytical and clinical applications. In this work, the capability of an insulator-based dielectrophoresis (iDEP) device for the detection and stable capture of low abundant polystyrene particles and yeast cells was evaluated. Binary and tertiary mixtures of particles and cells were tested, where the low abundant particles had concentration ratios on the order of 1:10 000 000 compared to the other particles present in the mixture. The results demonstrated successful and stable capture and enrichment of rare particles and cells (trapping efficiencies over 99%), where particles remained trapped in a stable manner for up to 4 min. A device with four reservoirs was employed for the separation and enrichment of rare particles, where the particles of interest were first selectively concentrated and then effectively directed to a side port for future collection and analysis. The present study demonstrates that simple iDEP devices have appropriate screening capacity and can be used for handling samples containing rare particles; achieving both enrichment and isolation of low abundant particles and cells. PMID- 26674136 TI - RELIABILITY OF TWO METHODS OF CLINICAL EXAMINATION OF THE FLEXIBILITY OF THE HIP ADDUCTOR MUSCLES. AB - BACKGROUND: An inadequate level of flexibility of the adductor muscles is one of the most critical risk factors for chronic groin pain and strains. However, measurement methods of adductor muscle flexibility are not well defined. PURPOSE: To determine the inter-session reliability of the biarticular and monoarticular adductor muscle flexibility measures obtained from passive hip abduction with the knee flexed over the edge of the plinth test (PHA) and the passive hip abduction test at 90 degrees of hip flexion (PHA90 degrees ). STUDY DESIGN: Clinical Measurement Reliability study. METHODS: Fifty healthy recreational athletes participated in this study. All participants performed the PHA and PHA90 degrees on four different occasions, with a two-week interval between testing sessions. Reliability was examined through the change in the mean between consecutive pairs of testing sessions (ChM), standard error of measurement expressed in absolute values (SEM) and as a percentage of the mean score (%SEM), minimal detectable change at 95% confidence interval (MDC95), and intraclass correlation coefficients (ICC2,k). RESULTS: The findings showed negligible or trivial ChM values for the two adductor flexibility measures analyzed (<2 degrees ). Furthermore, the SEM and MDC95 were 2.1 degrees and 5.9 degrees and 2.2 degrees and 6.2 degrees for the measures obtained from the PHA and PHA90 degrees , respectively, with %SEM scores lower than 5% and ICC scores higher than 0.90. CONCLUSION: The findings from this study suggest that the adductor muscle flexibility measures analyzed have good to excellent inter-session reliability in recreational athletes. Thus, clinicians can be 95% confident that an observed change between two measures larger than 5.9 degrees and 6.2 degrees for the flexibility measures obtained from the PHA and PHA90 degrees , respectively, would indicate a real change in muscle flexibility. LEVEL OF EVIDENCE: 2. PMID- 26674137 TI - Vanishing Mandible: A Rare Case Report with Accent to Recent Concepts on Aetio pathogenesis. AB - Massive osteolysis is a rare idiopathic bone disease resulting in progressive destruction of bone. Considering the rarity of encountering this fascinating bone disease, it is often misinterpreted as some other osteolytic disease. Hence, we present a well-documented case of massive osteolysis in a 29-year-old female patient with complete clinical, radiographic, macroscopic and microscopic features along with surgical photographs, which has been effectively managed at our hospital. PMID- 26674139 TI - Errors in the ultrasound diagnosis of the kidneys, ureters and urinary bladder. AB - The article presents the most frequent errors made in the ultrasound diagnosis of the urinary system. They usually result from improper technique of ultrasound examination or its erroneous interpretation. Such errors are frequent effects of insufficient experience of the ultrasonographer, inadequate class of the scanner, insufficient knowledge of its operation as well as of wrong preparation of patients, their constitution, severe condition and the lack of cooperation during the examination. The reasons for misinterpretations of ultrasound images of the urinary system may lie in a large polymorphism of the kidney (defects and developmental variants) and may result from improper access to the organ as well as from the presence of artefacts. Errors may also result from the lack of knowledge concerning clinical and laboratory data. Moreover, mistakes in ultrasound diagnosis of the urinary system are frequently related to the lack of knowledge of the management algorithms and diagnostic possibilities of other imaging modalities. The paper lists errors in ultrasound diagnosis of the urinary system divided into: errors resulting from improper technique of examination, artefacts caused by incorrect preparation of patients for the examination or their constitution and errors resulting from misinterpretation of ultrasound images of the kidneys (such as their number, size, fluid spaces, pathological lesions and others), ureters and urinary bladder. Each physician performing kidney or bladder ultrasound examination should possess the knowledge of the most frequent errors and their causes which might help to avoid them. PMID- 26674140 TI - Study on Subclinical Hypothyroidism and its Association with Various Inflammatory Markers. AB - INTRODUCTION: Subclinical hypothyroidism shows the mimic reaction more like to frank hypothyroidism which creates the dilemma. Inflammatory markers can be helpful in assessment of adverse effects of subclinical hypothyroidism, are not very well studied in the past. So the aim of this study was to investigate the role of inflammatory markers in Subclinical hypothyroidism patients. MATERIALS AND METHODS: The study population consisted of 154 patients with recently diagnosed subclinical hypothyroidism and 100 healthy controls. TSH, FT4 & T3 were estimated by enzyme linked Immunosorbent assay (ELISA) for diagnosis of subclinical hypothyroidism. Total cholesterol, triglycerides, and HDL-C were estimated by spectrophotometric method. LDL - C was calculated by Friedewald formula. Inflammatory markers (ESR, C-reactive protein & Interleukin 6) were also estimated by enzyme linked Immunosorbent assay (ELISA). RESULTS: In this study the level of TSH Mean +/- SD (11.12+/-4.17 vs 2.73+/-0.80) and T3 Mean +/- SD (0.96+/-0.17 vs 1.08+/-0.26) were significantly higher (<0.001) in subclinical hypothyroidism. Serum concentration of FT4 was not significantly different between the groups. Total cholesterol, triglycerides, and LDL-C were significantly higher in patients group. While the level of HDL-C was significantly lower in SCH patients compared to euthyroid group. TSH level was positively correlated with inflammatory markers in subclinical hypothyroidism, which were significantly different in subclinical hypothyroidism. CONCLUSION: This study suggests that subclinical hypo-thyroidism patients have increased inflammatory markers along with dyslipidemia and due to that future risk of further development of cardiovascular disorder can occur. Level of inflammatory markers increases in patients as disease progress if left untreated. PMID- 26674141 TI - An Assessment of Coliform Bacteria in Water Sources Near Appalachian Trail Shelters Within the Great Smoky Mountains National Park. AB - OBJECTIVE: Hikers and campers are exposed to risks while in the wilderness. One of these risks is the possibility of contracting an illness, including infectious diarrhea. This project tested for coliform bacteria in water samples taken near popular Appalachian Trail shelters. METHODS: Water was collected from access points within the Great Smoky Mountains National Park. Samples were collected in sterile bottles and inoculated on a commercially available coliform detection kit for quantitative determination of total coliform and Escherichia coli counts. RESULTS: Water samples were taken during summer and fall seasons. During summer, 7 of 10 samples were positive for coliform bacteria and 6 of those 7 for E coli. The most probable number (MPN) of colony-forming units (CFU) for coliform bacteria ranged from 0 to 489 CFU/100 mL, with the MPN for E coli varying from 0 to 123 CFU/100 mL. These data differed from the fall collection, revealing 3 of 7 samples positive for coliform bacteria and 1 of those 3 for E coli. The MPN of CFU for coliform bacteria in fall samples varied from 0 to 119 CFU/100 mL and 0 to 5 to CFU/100 mL for E coli. CONCLUSIONS: Environmental Protection Agency drinking water standards set the standard of 0 CFU/100 mL to be considered safe. This analysis of water samples along the Appalachian Trail emphasizes that the majority of water access points require treatment during the summer season. Coliform burden was not as high through the fall months. These data suggest one infectious disease risk for wilderness travelers. PMID- 26674138 TI - Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons. AB - BACKGROUND: Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. RESULTS: In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. CONCLUSION: These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents. PMID- 26674142 TI - Injuries and Fatalities on Sailboats in the United States 2000-2011: An Analysis of US Coast Guard Data. AB - BACKGROUND: Prior sailing injury studies have been small, focused investigations. This large, population-based study examined the mechanisms and factors contributing to sailboat-related injuries and deaths. METHODS: A retrospective data analysis of the Boating Accident Report Database compiled by the US Coast Guard between 2000 and 2011 was performed. The database was analyzed looking at frequency of events. For each subgroup, proportions were determined and 95% CIs were calculated. These data, used in conjunction with the 2011 US Coast Guard National Recreational Boating Survey, were used to estimate a fatality rate. RESULTS: Two hundred seventy-one sailing-related fatalities and 841 injuries were reported. A fatality rate was calculated at 1.19 deaths per million sailing person-days. Weather or hazardous waters were listed as primary contributing factors in 28.0% (95% CI, 22.7-33.4) of deaths; 70.1% (95% CI, 64.7-75.6) of deaths occurred after falling overboard or capsizing. Drowning was the most common cause of death (73.1%; 95% CI, 67.8-78.4), and 81.6% of victims were not wearing a life jacket. Alcohol intoxication contributed to 12.2% (95% CI, 8.3 16.1) of deaths. Operator- or passenger-preventable factors contributed to 52.7% (95% CI, 49.3-56.1) of all injuries; 51.6% (95% CI, 46.1-57.1) of injuries on nonmotorized sailboats were the result of capsizing, and 46.4% (95% CI, 42.1 50.7) of all injuries on motorized sailboats were the result of collisions or grounding. CONCLUSIONS: The calculated fatality rate is similar to that of alpine skiing. Falls overboard and capsizing were the most common fatal accidents. Operator inattention, inexperience, and alcohol use were common preventable factors contributing to fatal and nonfatal injury. PMID- 26674143 TI - Distribution of CD4(+) and CD8(+) T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking. AB - BACKGROUND AND OBJECTIVE: The immune system plays an important role in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the infiltration patterns of CD4(+) and CD8(+) T cells in NSCLC and to analyze their relation to COPD, smoking status and other clinicopathologic variables. MATERIALS AND METHODS: Lung tissue specimens from 50 patients who underwent surgery for NSCLC (stages I-III) and 10 control group subjects were analyzed immunohistochemically. RESULTS: NSCLC patients had a greater number of CD4(+) and CD8(+) T cells infiltrating the lung tissue than the control group (P=0.001) with predominant infiltration in the tumor stroma. We found a significant association between the number of total and tumor stroma infiltrating CD4(+) and CD8(+) T cells, and smoking status (P<0.05). There were more CD8(+) T cells in the tumor stroma and fewer in the tumor islets in NSCLC patients with COPD as compared to NSCLC patients without COPD (P<0.05). However, there was no such association between CD4(+) T cells and COPD status. A high level of CD8(+) T cell infiltration in the tumor stroma was independently associated with the coexistence of COPD in multivariate analysis (P<0.05). CONCLUSIONS: According to our data, COPD but not smoking seems to be associated with higher infiltration of CD8(+) T cells in the tumor stroma of patients with NSCLC. It allows us to hypothesize that NSCLC patients with coexisting COPD may have a more favorable outcome due to anticancer properties of stromal CD8(+) T cells. PMID- 26674144 TI - Factors associated with bone mineral density loss in patients with spondyloarthropathies: A 4-year follow-up study. AB - OBJECTIVE: To explore the relationship between laboratory, functional, disease activity markers and bone mineral density (BMD) loss in patients with spondyloarthropathies (SpAs). METHODS: A cohort of 41 SpA patients were followed up for 4 years. Disease activity indices, spinal mobility and laboratory tests, BMD using were monitored at the baseline and 4-year follow-up. The 4% BMD loss at either of the proximal femurs was defined as significant. RESULTS: Over the 4 year study period, 27% of SpA patients experienced femoral BMD loss. Baseline BMD>0.85g/cm(2) (p=0.011) was the baseline factor associated with BMD loss at 4 year follow-up. Several clinical and functional tests were helpful in identifying the BMD loss at follow-up: CRP>15.6mg/L (sens. 91%, spec. 70%), ESR>29mm/h (sens. 82%, spec. 73%), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)>4.75 (sens. 91%, spec. 62%). At follow-up anti-TNFalpha treatment history, stable or improved lateral flexion and intermalleolar distance (NPV, accordingly, 95%, 88% and 87%), made BMD loss unlikely. Deterioration of the physician assessment of global disease activity (PAGDA) score from baseline to follow-up was a remarkable predictor of BMD loss (PPV=0.83), while stable or improved score excluded the BMD loss (NPV=0.83). According to multiple logistic regression analysis, baseline BMD value and follow-up CRP levels, when considered together, identify BMD status correctly in 85% of SpA patients (Nagelkerke R(2)=0.676). CONCLUSION: Baseline BMD, anti-TNFalpha treatment, PAGDA score, spinal mobility tests and disease activity markers are useful factors in predicting the BMD loss in SpA patients and can provide surrogate information on BMD status. PMID- 26674145 TI - Cesarean section rates in Lithuania using Robson Ten Group Classification System. AB - BACKGROUND AND OBJECTIVE: The aim of this study was to analyze cesarean section (CS) rates using Robson Ten Group Classification System (TGCS) and to identify the main contributors to the overall CS rate in Lithuania. MATERIALS AND METHODS: A prospective cross-sectional study was carried out. All women who delivered between January 1 and December 31, 2012, in Lithuania were classified using the TGCS. The CS rates overall and in each Robson group were calculated, as was the contribution of each group to the overall CS rate. RESULTS: The CS rate was 26.4% (6697 among 25,373 deliveries) in 2012. Nulliparous women with single cephalic full-term pregnancy in spontaneous labor (Group 1) or who underwent induction of labor or prelabor CS (Group 2) and multiparous women with a previous CS (Group 5) were the greatest contributors (67.7%) to the overall CS rate. In addition, significant variation of CS rates between different institutions was observed, especially in women with single cephalic full-term pregnancy without previous CS (Groups 1-4), showing big differences in obstetric care across country. CONCLUSIONS: Women in Groups 1, 2 and 5 were the largest contributions to the overall CS rate in Lithuania. It seems that efforts to reduce the overall CS rate should be directed on increasing vaginal birth after CS and reducing CS rates in nulliparous women with single cephalic full-term pregnancy (Groups 1 and 2). PMID- 26674146 TI - Correlation between throat-related symptoms and histological examination in adults with chronic tonsillitis. AB - OBJECTIVE: The aim of the study was to evaluate correlations between throat related symptoms and histological findings in adults with chronic tonsillitis. MATERIALS AND METHODS: A prospective cohort study was carried out. Throat-related symptoms (complaints, tonsillitis rate, and pharyngeal findings) of 81 adults with histologically proven chronic tonsillitis followed by tonsillectomy were analyzed. Four types of histological changes in removed tonsils were determined: (1) pure hyperplasia, (2) chronic inflammation, (3) chronic inflammation with hyperplasia, (4) chronic inflammation with scarring/fibrosis. The power of correlation was tested using the Pearson contingency coefficient (CC). RESULTS: Recurrent throat infections were the most common complaint (74.1%). The mean tonsillitis rate was 3.6 (SD 1.9) episodes per year. Tonsillar cryptic debris (61.7%) and hyperemia of the anterior pillars (59.3%) were the most common pharyngeal findings. Chronic inflammation with hyperplasia was predominant (38.3%) histological type of chronic tonsillitis. The statistically significant correlations between histological type and combination of tonsillitis rate >=3 times per year with cryptic debris (CC=0.346; P=0.010) and cryptic debris alone (CC=0.294; P=0.051) were detected. CONCLUSIONS: Assessment of throat-related symptoms is complementary to histological examination in adults with chronic tonsillitis. PMID- 26674147 TI - The influence of the extended indications for sentinel node biopsy on the identification of metastasis-free and metastatic sentinel nodes. AB - BACKGROUND AND OBJECTIVE: Rates of sentinel node (SN) identification and metastasis-positive SNs were compared between the group with highly selective indications for sentinel node biopsy (SNB) and the group with merely no contraindications for SNB (Groups A and B, respectively). MATERIALS AND METHODS: We performed a single-center retrospective data analysis of 471 breast cancer patients treated during 2004-2010. Data on clinical and pathologic staging, frozen section results, radiological measurements and pathologic examination results were obtained from patient records. Patients were analyzed in two groups. Group A (n=143) had SNB performed only when the patients fulfilled to the following criteria: breast tumor no greater than 3cm in diameter, unifocal disease, no pure ductal carcinoma in situ, no history of previous breast or lymph node surgery, and no neoadjuvant chemotherapy. Indications for SNB were extended in Group B (n=328) so that inflammatory breast cancer and positive lymph nodes became the only exclusion criteria. RESULTS: The rate of SN identification was 97.9% in Group A vs. 99.09% in Group B (P=0.29). SNs were metastasis positive and frozen sections false negative at comparable proportions in both groups. CONCLUSIONS: The extension of indications for SNB did not reduce the rates of SN identification or did not create any impact on the rate of metastatic SNs. PMID- 26674148 TI - Treatment procedures and referral patterns of general dentists in Lithuania. AB - BACKGROUND AND OBJECTIVE: The requirement for dental specialties and the number of specialists in each country depends on the content and execution of undergraduate dental education, the complex oral health care needs of the society and other factors. The aim of our study was to assess specific treatment procedures of Lithuanian general dentists and their need to refer patients to specialists. MATERIALS AND METHODS: Census sampling was employed and the data collected by means of a structured questionnaire asking dentists about the frequency of specific treatment procedures they perform and the frequency of referrals they make to different dental specialists. The results are of a self reported nature. RESULTS: From general dental practice, 76.3% of cases needing orthodontic treatment were referred to orthodontists. About half of patients needing specialized care were referred to periodontists (50.2%), orthopedists (46.9%) and oral surgeons (45.0). More than one-third (39%) of the cases needing specialist care were referred to endodontists. Only one-third of patients were referred to pediatric dentists. In about 60% of cases needing respective care general dentists extracted teeth and roots, made incisions in acute jaw infections and treated young children; in about half of cases general dentists performed complex endodontic manipulations and treatment with fixed and removable prostheses. CONCLUSIONS: There is a clear need for Lithuanian dental practitioners to refer patients to all types of dental specialists. Undergraduate dental education program and postgraduate training should be more directed toward the extraction of teeth and roots, treatment of young children and provision of dental prostheses to patients. PMID- 26674149 TI - Evaluation of low-dose proton beam radiation efficiency in MIA PaCa-2 pancreatic cancer cell line vitality and H2AX formation. AB - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the efficiency of proton beam irradiation in pancreatic cancer cell line MIA PaCa-2 and its role in the cell cycle, apoptosis, and formation of histone gammaH2AX in different reparation times (72-h follow-up). MATERIAL AND METHODS: The MIA PaCa-2 pancreatic carcinoma cell line was irradiated with 1.6-Gy proton beam. After irradiation, cell viability was measured colorimetrically, and the cell cycle, apoptosis, and gammaH2AX expression were evaluated on a FACScan cytometer. RESULTS: Low-dose proton beam irradiation had an effect on the MIA PaCa-2 tumor cell line already 1h after exposure, but maximal lethality was reached after 72h postirradiation with a cell viability rate of 24%. The cell cycle went into partial G1/0 arrest, and was released after 72h. The expression of gammaH2AX was strong and its levels were significantly elevated as late as 48h post radiation. The apoptosis levels increased with post radiation incubation time to reach 79% after 72h. CONCLUSIONS: Our data demonstrate that low-doses proton beam irradiation had an effect on MIA PaCa-2 pancreatic carcinoma cell line. Full extent of irradiation had an impact only 24h postirradiation, triggering DNA arrested cell cycle in G1/0 phase. Formed DNA DSBs were found to be repaired via the NHEJ pathway mechanism within 72h. Unsuccessful repaired DSBs induced apoptotic cell death. After 72h reparation processes were completed, and cell cycle was released from arrest in G1/0 phase. PMID- 26674150 TI - Spinal posture in different DanceSport dance styles compared with track and field athletes. AB - BACKGROUND AND OBJECTIVE: In DanceSport, athletes train for many years to develop a very specific posture. Presently there are few data as to whether these adaptations are habitual or cause permanent anatomical changes to the spine. The aim of the current study was to evaluate lumbar lordosis and thoracic kyphosis of the international level DanceSport dancers using track and field athletes as controls. MATERIALS AND METHODS: Thirty competitive DanceSport couples (15 men aged 23.4+/-6.6 years; 15 women aged 22.5+/-6.4 years) and 29 track and field athletes (16 mean aged 27+/-4.4 years and 13 women aged 22+/-4.1 years) volunteered. Twelve couples were Standard, 7 Latin American and 11 were Ten Dance couples. Thoracic kyphosis and lumbar lordosis angle were assessed in lateral view using a Vertebral Fracture Assessment scan. RESULTS: DanceSport athletes had smaller S-shaped vertebral curvatures compared to track and field athletes. Male (5.7+/-4.7 degrees ) and female dancers (8.7+/-5.9 degrees ) had significantly smaller lumbar lordosis angle compared to their track and field counterparts (22.3+/-9.9 degrees for men; 20.3+/-5.9 degrees for women). Female dancers (25.3+/-8.0 degrees ) also demonstrated significantly smaller thoracic kyphosis angle than female track and field (32.1+/-8.9 degrees ) participants. It was further revealed that female Latin American dancers had significantly smaller lumbar lordosis values (3.7+/-3.1 degrees ) compared with female Standard (10.7+/ 6.1 degrees ) and Ten Dance dancers (9.7+/-5.5 degrees ). CONCLUSIONS: The results of the present study suggest that smaller S-shaped vertebral curvatures of DanceSport athletes compared with track and field athletes are permanent changes rather than habitual. PMID- 26674151 TI - Regional inequalities of hospital morbidity and associations with mortality in Lithuania. AB - BACKGROUND AND OBJECTIVE: In Lithuania, hospitalization was planned to be reduced with the approval of the national healthcare restructuring program. The aim of this study was to describe regional inequalities of hospitalization and hospital morbidity in Lithuania and to associate them with mortality in the regions. MATERIALS AND METHODS: Routine hospital discharge data of Lithuanian hospitals, reimbursed by the Compulsory Health Insurance Fund and registered in database SVEIDRA, was used. Age-adjusted general hospitalization and hospital morbidity rates (per 1000 population) due to cardiovascular diseases (CVD), malignant neoplasms and external causes were calculated. Contribution of diseases, causing major public health problems, to general hospitalization was evaluated by analysis of components. Association of general hospitalization or hospital morbidity and mortality of respective causes was evaluated using non-parametric Spearman correlation. RESULTS: General hospitalization and hospital morbidity of CVD, malignant neoplasms and external causes had increased from 2005 to 2011. Inequalities of hospitalization and hospital morbidity existed between regions of Lithuania. In Siauliai, Klaipeda, Utena and Panevezys regions, general hospitalization remained higher than national level. In Marijampole, Alytus and Kaunas regions, general hospitalization became lower than Lithuanian average. There was no statistically significant correlation between variation in hospitalization and mortality rates in the regions. CONCLUSIONS: Despite national efforts to decrease hospital care, our study detected the failure of hospitalization reduction and revealed an increase of hospitalization with the existing regional inequalities in Lithuania. PMID- 26674152 TI - Molecular basis and functional significance of Angiotensin II-induced increase in Discoidin Domain Receptor 2 gene expression in cardiac fibroblasts. AB - Delineation of mechanisms underlying the regulation of fibrosis-related genes in the heart is an important clinical goal as cardiac fibrosis is a major cause of myocardial dysfunction. This study probed the regulation of Discoidin Domain Receptor 2 (DDR2) gene expression and the regulatory links between Angiotensin II, DDR2 and collagen in Angiotensin II-stimulated cardiac fibroblasts. Real-time PCR and western blot analyses showed that Angiotensin II enhances DDR2 mRNA and protein expression in rat cardiac fibroblasts via NADPH oxidase-dependent reactive oxygen species induction. NF-kappaB activation, demonstrated by gel shift assay, abolition of DDR2 expression upon NF-kappaB inhibition, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of DDR2 by NF-kappaB in Angiotensin II-treated cells. Inhibitors of Phospholipase C and Protein kinase C prevented Angiotensin II-dependent p38 MAPK phosphorylation that in turn blocked NF-kappaB activation. Angiotensin II also enhanced collagen gene expression. Importantly, the stimulatory effects of Angiotensin II on DDR2 and collagen were inter-dependent as siRNA-mediated silencing of one abolished the other. Angiotensin II promoted ERK1/2 phosphorylation whose inhibition attenuated Angiotensin II-stimulation of collagen but not DDR2. Furthermore, DDR2 knockdown prevented Angiotensin II induced ERK1/2 phosphorylation, indicating that DDR2-dependent ERK1/2 activation enhances collagen expression in cells exposed to Angiotensin II. DDR2 knockdown was also associated with compromised wound healing response to Angiotensin II. To conclude, Angiotensin II promotes NF-kappaB activation that up-regulates DDR2 transcription. A reciprocal regulatory relationship between DDR2 and collagen, involving cross-talk between the GPCR and RTK pathways, is central to Angiotensin II-induced increase in collagen expression in cardiac fibroblasts. PMID- 26674153 TI - The prognostic significance of tumour-stroma ratio in endometrial carcinoma. AB - BACKGROUND: High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters. METHODS: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n=400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen's Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons. RESULTS: TSR as a continuous variable associated with worse OS (P=0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR=2.51; 95% CI=1.22-5.12; P=0.021) and DFS (HR=2.19; 95% CI=1.15 4.17; P=0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P<0.001) and lymphovascular space invasion (P<0.001), both of which had independent prognostic significance in this study population. CONCLUSIONS: Low tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many--although not all--cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types. PMID- 26674154 TI - Aspartate transaminase to platelet ratio index in hepatitis C virus and Schistosomiasis coinfection. AB - AIM: To assess the diagnostic accuracy, of aminotransferase-to-platelet ratio index (APRI) alone and with antischistosomal antibody (Ab) in patients with hepatitis C virus (HCV) and schistosomiasis coinfection. METHODS: This retrospective study included medical records of three hundred and eighty three Egyptian men patients who had undergone percutaneous liver biopsy between January 2006 to April 2014 in tertiary care hospital in Qatar for diagnosis or monitoring purpose were selected. Data of patients > 18 years of age were included in the study. The values of HCV RNA titer and antischistosomal antibody titer were also taken into consideration. Patients were excluded from the study if they had any other concomitant chronic liver disease, including; history of previous antiviral or interferon therapy, immunosuppressive, therapy, chronic hepatitis B infection, human immunodeficiency virus co-infection, autoimmune hepatitis, decompensated liver disease, hepatocellular carcinoma, prior liver transplantation, and if no data about the liver biopsy present. RESULTS: Median age of patients was 46 years. About 7.1% had no fibrosis, whereas 30.4%, 37.5%, 20.4%, and 4.6% had fibrosis of stage I, II, III, and IV respectively. In bivariate analysis, APRI score, levels of AST, platelet count and age of patient showed statistically significant association with liver fibrosis (P < 0.0001); whereas antischistosomal antibody titer (P = 0.52) and HCV RNA titer (P = 0.79) failed to show a significant association. The respective AUC values for no fibrosis, significant fibrosis, severe fibrosis and cirrhosis of APRI score were 63%, 73.2%, 81.1% and 88.9% respectively. This showed good sensitivity and specificity of APRI alone for grading of liver fibrosis. But the inclusion of anti Schistosoma antibody did not improve the prediction of fibrosis stage. CONCLUSION: The study results suggest that noninvasive biochemical markers like APRI are sensitive and specific in diagnosing the degree of fibrosis and cirrhosis in patients with coinfection of HCV and schistosomiasis as compared to biopsy. The addition of antischistosomal Ab to APRI did not improve sensitivity for predicting the degree of cirrhosis. PMID- 26674155 TI - Multimodal navigated skull base tumor resection using image-based vascular and cranial nerve segmentation: A prospective pilot study. AB - BACKGROUND: Skull base tumors frequently encase or invade adjacent normal neurovascular structures. For this reason, optimal tumor resection with incomplete knowledge of patient anatomy remains a challenge. METHODS: To determine the accuracy and utility of image-based preoperative segmentation in skull base tumor resections, we performed a prospective study. Ten patients with skull base tumors underwent preoperative 3T magnetic resonance imaging, which included thin section three-dimensional (3D) space T2, 3D time of flight, and magnetization-prepared rapid acquisition gradient echo sequences. Imaging sequences were loaded in the neuronavigation system for segmentation and preoperative planning. Five different neurovascular landmarks were identified in each case and measured for accuracy using the neuronavigation system. Each segmented neurovascular element was validated by manual placement of the navigation probe, and errors of localization were measured. RESULTS: Strong correspondence between image-based segmentation and microscopic view was found at the surface of the tumor and tumor-normal brain interfaces in all cases. The accuracy of the measurements was 0.45 +/- 0.21 mm (mean +/- standard deviation). This information reassured the surgeon and prevented vascular injury intraoperatively. Preoperative segmentation of the related cranial nerves was possible in 80% of cases and helped the surgeon localize involved cranial nerves in all cases. CONCLUSION: Image-based preoperative vascular and neural element segmentation with 3D reconstruction is highly informative preoperatively and could increase the vigilance of neurosurgeons for preventing neurovascular injury during skull base surgeries. Additionally, the accuracy found in this study is superior to previously reported measurements. This novel preliminary study is encouraging for future validation with larger numbers of patients. PMID- 26674156 TI - Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis. AB - BACKGROUND: Stroke prevention by warfarin, a vitamin K antagonist, has been an integral part in the management of atrial fibrillation. Vitamin K-dependent matrix Gla protein (MGP) has been known as a potent inhibitor of arterial calcification and osteoporosis. Therefore, we hypothesized that warfarin therapy affects bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. METHODS: We studied 42 atrial fibrillation patients at high-risk for atherosclerosis having one or more coronary risk factors. Twenty-four patients had been treated with warfarin for at least 12 months (WF group), and 18 patients without warfarin (non-WF group). Bone alkaline phosphatase (BAP) and under carboxylated osteocalcin (ucOC) and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured as bone metabolism markers. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index measured by Endo-PAT2000 was used as an indicator of vascular endothelial function. RESULTS: There were no significant differences in patient background characteristics and other clinical indicators between the two groups. In WF group, the ucOC levels were significantly higher than those in the non-WF group (10.3 +/- 0.8 vs. 3.4 +/- 0.9 ng/mL; P < 0.01), similarly, the RANKL levels in the WF group were higher than those in the non-WF group (0.60 +/- 0.06 vs. 0.37 +/- 0.05 ng/mL; P = 0.007). Moreover, RH-PAT index was significantly lower in the WF group compared to those in the non-WF group (1.48 +/- 0.11 vs. 1.88 +/- 0.12; P = 0.017). CONCLUSIONS: Long-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60 80 year old hypertensive patients. PMID- 26674157 TI - Petatewalide B, a novel compound from Petasites japonicus with anti-allergic activity. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The giant butterbur Petasites japonicus is used to treat asthma and allergic diseases in traditional Korean, Japanese, and Chinese medicine. AIM OF THE STUDY: To elucidate the anti-allergic effect of Petasites genus, we studied effects of several compounds from Petasites japonicus leaves and found a novel bakkenolide-type sesquiterpine. In the present study, anti-allergic and anti-inflammatory effects of the new compound was examined using in vivo and in vitro experiments. MATERIALS AND METHODS: The novel compound was isolated from Petasites japonicus leaves and named petatewalide B. Antigen induced degranulation and Ca(2+) mobilization were measured in RBL-2H3 mast cells by measuring beta-hexosaminidase activity and fluorescence change of Ca(2+) probe, fura-2. Induction of inducible nitric oxide synthase and cyclooxygenase 2 was measured by Western blotting in peritoneal macrophages. In addition, ovalbumin-induced asthma model was used for in vivo efficacy test of petatewalide B. Membrane potential was estimated by measuring fluorescence change of DiBAC in C6 glioma cells. RESULTS: Petatewalide B inhibited the antigen-induced degranulation of beta-hexosaminidase in RBL-2H3 mast cells, but did not affect antigen-induced Ca(2+) increase in the cells. Petatewalide B also showed inhibition of the LPS-induced induction of iNOS, but not COX-2 in mouse peritoneal macrophages. Nitric oxide production was also inhibited by petatewalide B in macrophages. In the ovalbumin-induced asthma model, petatewalide B strongly inhibited accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Petatewalide B increased the membrane potential of C6 glioma cells in a concentration-dependent manner. CONCLUSION: Petatewalide B from Petasites genus not only has anti-allergic and anti-inflammatory effects but also induces a transient increase of membrane potential in C6 glioma cells. PMID- 26674158 TI - Cleistochlamys kirkii chemical constituents: Antibacterial activity and synergistic effects against resistant Staphylococcus aureus strains. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cleistochlamys kirkii (Benth) Oliv., (Annonaceae) is a medicinal plant traditionally used in Mozambique to treat infectious diseases. AIMS OF THE STUDY: To find antibacterial lead compounds from C. kirkii and provide scientific validation for its use in traditional medicine. MATERIALS AND METHODS: Through bioassay-guided fractionation, nine compounds (1-9), with different scaffolds, were isolated from the methanol extract of C. kirkii whose structures were identified by spectroscopic methods. Compounds 1-9 were evaluated for their in vitro antibacterial activity against a panel of eight Gram-positive, including five drug-resistant strains of Staphylococcus aureus, vancomycin resistant Enterococcus faecalis, and two Gram-negative bacteria strains. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. A chemosensitization assay, using the checkerboard method, was also performed in order to evaluate the type of interaction of compounds with antibiotics/compounds against two S. aureus resistant strains (ATCC 9144 and CIP 106760) and a susceptible strain (ATCC 6538). RESULTS: Dichamanetin (3), a rare C benzylated flavanone, was very active against all the Gram-positive strains tested, displaying MIC values in the range of 1-7.5 MUg/mL. The C-benzylated flavanones chamanetin (1), isochamanetin (2), and the alpha,beta-unsaturated lactone (-)-cleistenolide (6) also showed relevant antibacterial activity against some of the Gram-positive strains assayed. Compounds 4, 5, and 7-9 have shown no significant activity at the concentration ranges tested. In the combination with antibiotics, polycarpol (8) (MIC 125 MUg/mL) showed a strong synergistic effect against the methicillin-resistant S. aureus ATCC 9144. When combined with oxacillin (MIC 125 MUg/mL), compound 8 reduced the MIC to 1.5 MUg/mL (FICI=0.11). Similarly, it reduced the MIC of amoxicillin (MIC 250 MUg/mL) to 7.5 MUg/mL (FICI=0.18). Synergy was also obtained when this compound was combined with both beta-lactam antibiotics (FICI=0.30) and with vancomycin (FICI=0.24) against vancomycin-intermediate S. aureus (VISA) CIP 106760. Remarkable, compound 8 was also able to reduce synergistically the MIC value of dichamanetin (3) (FICI=0.18) against this strain. CONCLUSIONS: These results suggested that C. kirkii constituents may be valuable as a leads for restoring antibiotic activity against resistant S. aureus strains. PMID- 26674159 TI - Cassia obtusifolia seed ameliorates amyloid beta-induced synaptic dysfunction through anti-inflammatory and Akt/GSK-3beta pathways. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tea infused with the seed of Cassia obtusifolia has been traditionally used as an herbal remedy for liver, eye, and acute inflammatory diseases. Recent pharmacological reports have indicated that Cassiae semen has neuroprotective effects, attributable to its anti-inflammatory actions, in ischemic stroke and Parkinson's disease models. AIM OF THE STUDY: Previously, the ethanol extract of C. obtusifolia seeds (COE) was reported to have memory enhancing properties. However, the effects of COE in an Alzheimer's disease (AD) model are currently unknown. In this study, we investigated the effect(s) of COE on aberrant synaptic plasticity and memory impairment induced by amyloid beta (Abeta), a key toxic component found in the AD brain. MATERIALS AND METHODS: To determine the effect of COE on Abeta-induced aberrant synaptic plasticity, we used acute mouse hippocampal slices and delivered theta burst stimulation to induce long-term potentiation (LTP). Western blots were used to detect Abeta- and/or COE-induced changes in signaling proteins. The novel object location recognition test was conducted to determine the effect of COE on Abeta-induced recognition memory impairment. RESULTS: COE was found to ameliorate Abeta-induced LTP impairment in the acute hippocampal slices. Glycogen synthase kinase-3beta (GSK-3beta), a key molecule in LTP impairment, was activated by Abeta. However, this process was inhibited by COE via Akt signaling. Moreover, COE was found to attenuate Abeta-induced microglia, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX) activation. In the in vivo studies performed, COE ameliorated the Abeta-induced object recognition memory impairment. CONCLUSION: These results suggest that COE exhibits neuroprotective activities against Abeta induced brain disorders. PMID- 26674160 TI - Asaia lannensis bacteremia in a 'needle freak' patient. AB - The genus Asaia has gained much interest lately owing to constant new species discoveries and its role as a potential opportunistic pathogen to humans. Here we describe a transient bacteremia due to Asaia lannensis in a patient with a psychiatric disorder (compulsive self-injection of different substances). Common phenotypic methods of identification failed to identify this organism, and only restriction fragment lenght polymorphism of PCR-amplified 16S rRNA gene allowed for proper identification. The isolate was highly resistant to most antibiotics. The paper also discusses the currently available medical literature, acknowledges the potential problems linked to the isolation of these strains and proposes an approach to species identification that can be applied in a clinical microbiology laboratory. PMID- 26674161 TI - Surgical complications following ESIN for clavicular mid-shaft fractures do not limit functional or patient-perceived outcome. AB - Elastic intramedullary nailing (ESIN) has been proposed as an alternative minimal invasive method for the operative management of mid-shaft fractures of the clavicle. However, a relevant complication rate has been reported in previous cohorts. The present retrospective single-centre study aimed to analyse the complications following ESIN in adult patients with clavicular mid-shaft fractures (Allman type I) and their impact on functional and patient-perceived outcome measures. Results were compared to a control group receiving locking plate osteosynthesis. The clinical course and outcome of operatively managed patients with clavicular mid-shaft fractures were retrospectively analysed. Patients were assigned to group A (ESIN) and group B (plate fixation). Radiological, functional (Constant Murley Shoulder Outcome Score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) Score, the Oxford Shoulder Score (OSS)), and patient perceived aesthetic and clinical outcome were measured. A total of 47 (33 male, 14 female) operatively managed patients with a mean age of 26.7 +/- 14.9 years and a follow up time of 38.1 +/- 19.4 months were analysed. 36 patients were treated by ESIN (Group A), whereas 11 patients received open reduction and internal plate fixation (Group B). Patients were operatively treated with a mean delay of 7.4 +/- 9.3 days (group A: 6.6 +/- 8.7 days, group B: 10.2 +/- 11.1 days, p=0.326) between trauma and the surgical index procedure. There were no significant differences in the functional (CS: p=0.338, DASH: p=0.247, OSS: p=0.434) and patient-perceived (p=0.346) outcome measures between both groups. Surgical complications were noted in 14 patients (group A: 12, group B: 2) and non-union in 4 patients (group A: 3, group B: 1). There was no correlation between the recorded complications as assessed by the Clavien and Dindo classification and the functional as well as the patient-perceived outcome measures. Despite a relevant incidence rate of surgical complications, ESIN provides good to excellent functional and patient-perceived results in the treatment of clavicular mid-shaft fractures. PMID- 26674162 TI - Health behaviour of miners. AB - BACKGROUND: What significantly affects the health of an individual health behaviour. It is of particular importance in the case of people working in very harsh environmental conditions. The aim of this study is to examine health behaviour among miners. MATERIAL AND METHODS: The research data was collected with the use of the diagnostic survey method based on the Health Behaviour Inventory questionnaire developed by Juczynski. Two hundred coal miners were surveyed. The results obtained were subjected to a statistical analysis. A significance level of p < 0.05 was assumed, which indicates the occurrence of statistically significant differences or relations. RESULTS: The level of health behaviour among miners may be determined as medium and low. The research group obtained the best results with regard to their mental attitude, while their preventive behaviour received the worst evaluation. CONCLUSIONS: The research confirms the necessity of implementing health promotion programmes among miners, which would be focusing particularly on health behaviour. PMID- 26674163 TI - Is water in dental units microbiologically safe? AB - BACKGROUND: Water supplied to the dental units must be of sufficient quality. The article presents the results of the microbiological analysis of cold municipal water which flows into a patient's disposable mouthwash cup, and demineralized water which flows through a waterline into the tool panel of a dental unit from the tank placed in the water group. MATERIAL AND METHODS: In order to assess the degree of purity (impurities) of water used in dental units, 2 series of microbiological tests were carried out in 6 dental surgeries from April to June, 2013. The water samples for microbiological testing were collected into sterile microbiological bottles in accordance with the current methodology. The water for the tests was collected from a sterile cup-filling tap (municipal water) and from an air/water syringe (demineralized water). The bacteria were cultured according to the Polish Standards - PN-EN ISO 6222, PN-EN ISO 9308-1, and PN-EN ISO 16266. RESULTS: In the tested samples of water numerous psychrophilic bacteria (max 29 100 CFU/ml) and mesophilic bacteria (max 24 700 CFU/ml), including single coliforms, were found. CONCLUSIONS: The results show that water delivered to a dental unit should be periodically tested bacteriologically and in terms of physical and chemical properties. Water systems of dental units should also be periodically disinfected to eliminate bacteria and biofilm. PMID- 26674164 TI - Back and neck pain among school teachers in Poland and its correlations with physical activity. AB - BACKGROUND: Back pain represents one of the most common diseases across various populations of workers worldwide. This study analyzes the prevalence and severity of back pain, based on selected demographic variables, and the relationship with physical activity among school teachers. MATERIAL AND METHODS: The study included 998 professionally active teachers (840 females and 158 males) from the southern part of Poland. Validated psychometric tools, namely: 1) for evaluation of disability due to back pain - a Polish version of the Oswestry Disability Index (ODI) and Neck Disability Index (NDI), 2) for physical activity assessment - the Subjective Experience of Work Load (SEWL) as well as the authors' supplementary questionnaire, addressing demographic and anthropometric variables were used. RESULTS: There was no correlation between age and the NDI scores in females (r = 0.027), in contrast to males (r = 0.202; p <= 0.05). Statistically significant correlations (p <= 0.05) were reported between: age and the ODI, in both females (r = 0.219) and males (r = 0.180). No associations between the body mass index (BMI)-ODI, and BMI-NDI were found. In the case of women, disability related to low back pain (LBP) had a negative impact on the indicators of their activity during work, sports, and leisure time. In the case of men, the NDI and ODI scores did not differ, based on activity indicators. CONCLUSIONS: Our findings confirm that back pain represents a serious concern among teachers. Age appears to be a prognostic factor, while no association between the BMI and LBP has been revealed. The limitation of physical activity leads to more frequent back pain. PMID- 26674166 TI - [Temperament vs. chronic fatigue in police officers]. AB - BACKGROUND: Chronic fatigue is a problem affecting a still growing number of people. Among them there are representatives of different professions who are forced to cope not only with occupational stress, but also with the problem of fatigue. The police is one of such occupational groups, in which exposure to stressful and often traumatic situations, contact with those who violate the law, shift work and contact with superiors can play a key role in the development of chronic fatigue. However, chronic fatigue, induced by the above mentioned factors, does not affect all police officers since its occurrence also depends on many personal traits, including temperament. MATERIAL AND METHODS: We studied a group of 61 police officers of the Kuyavian-Pomeranian garrison. The study was conducted using the Buss and Plomin EAS (emotionality, activity, sociability) Temperament Questionnaire, CIS-20R (community, innovation, survey) Questionnaire, developed by Vercoulen et al. and a questionnaire on socio-demographic data. RESULTS: The results indicated the relationship between chronic fatigue and emotionality. Statistical analyses showed a negative correlation between the nature of emotional components, distress, fear, anger, and the general rate of chronic fatigue. There was no statistically significant correlation between age, and service experience and the level of chronic fatigue. CONCLUSIONS: The results indicate that the officers of the study group show dramatically high levels of chronic fatigue. The results also revealed that temperament characteristics, such as sociability and activity, reported in the literature as factors reducing fatigue and stress, did not show relevance to chronic fatigue in the study group. PMID- 26674165 TI - [Bacterial and fungal aerosols in the work environment of cleaners]. AB - BACKGROUND: Cleaning services are carried out in almost all sectors and branches of industry. Due to the above, cleaners are exposed to various harmful biological agents, depending on the tasks performed and the commercial sector involved. The aim of this study was to assess the exposure of cleaning workers to biological agents based on quantitative and qualitative characteristics of airborne microflora. MATERIAL AND METHODS: A six-stage Andersen sampler was used to collect bioaerosols during the cleaning activities in different workplaces, including schools, offices, car services, healthy services and shops. Standard Petri dishes filled with blood trypticase soy agar and malt extract agar were used for bacterial and fungal sampling, respectively. RESULTS: The bioaerosol concentration values obtained during testing of selected workposts of cleaners were lower than the Polish recommended threshold limit values for microorganisms concentrations in public service. The most prevalent bacterial species in studied places were Gram-positive cocci (mainly of genera Micrococcus, Staphylococcus) and endospore-forming Gram-positive rods (mainly of genera Bacillus). Among the most common fungal species were those from genera Penicillium and Aspergillus. The size distribution analysis revealed that bioaerosols present in the air of workposts at shops, schools and car services may be responsible for nose and eye mucosa irritation and allergic reactions in the form of asthma or allergic inflammation in the cleaning workers. CONCLUSIONS: The study shows that occupational activities of cleaning workers are associated with exposure to airborne biological agents classified into risk groups, 1. and 2., according to their level of infection risk, posing respiratory hazard. PMID- 26674167 TI - [Electromagnetic fields in the vicinity of DECT cordless telephones and mobile phones]. AB - BACKGROUND: Mobile telephones belong to the most frequently used personal devices. In their surroundings they produce the electromagnetic field (EMF), in which exposure range there are not only users but also nearby bystanders. The aim of the investigations and EMF measurements in the vicinity of phones was to identify the electric field levels with regard to various working modes. MATERIAL AND METHODS: Twelve sets of DECT (digital enhanced cordless telecommunications) cordless phones (12 base units and 15 handsets), 21 mobile telephones produced by different manufactures, and 16 smartphones in various applications, (including multimedia) in the conditions of daily use in living rooms were measured. Measurements were taken using the point method in predetermined distances of 0.05 1 m from the devices without the presence of users. RESULTS: In the vicinity of DECT cordless phone handsets, electric field strength ranged from 0.26 to 2.30 V/m in the distance of 0.05 m - 0.18-0.26 V/m (1 m). In surroundings of DECT cordless telephones base units the values of EMF were from 1.78-5.44 V/m (0.05 m) to 0.19- 0.41 V/m (1 m). In the vicinity of mobile phones working in GSM mode with voice transmission, the electric field strength ranged from 2.34-9.14 V/m (0.05 m) to 0.18-0.47 V/m (1 m) while in the vicinity of mobile phones working in WCDMA (Wideband Code Division Multiple Access) mode the electric field strength ranged from 0.22-1.83 V/m (0.05 m) to 0.18-0.20 V/m (1 m). CONCLUSIONS: The mean values of the electric field strength for each group of devices, mobile phones and DECT wireless phones sets do not exceed the reference value of 7 V/m, adopted as the limit for general public exposure. PMID- 26674168 TI - [Realities of the prophylactic health care of workers in Poland]. AB - BACKGROUND: The Polish occupational health system (OHS), existing over the past 17 years, has recently been contested as never before. Critical voices pertain to both legislative and executive aspects of the system, in which key roles are played by employers and occupational medicine service. There are some reasons for making a hypothesis that relevant norms are not always respected by the main actors. MATERIAL AND METHODS: The data on the observance of norms by entities responsible for providing workers with prophylactic health care were analyzed. They were obtained from the existing external resources and materials collected during the implementation of tasks assigned by the Ministry of Health. RESULTS: Legal norms, which constitute OHS in Poland are generally neither respected by the employers, nor by the representatives of occupational medicine service. Nearly half (45-47%) of employers infringe provisions relating to medical examinations of workers. Such a degree of non-observance of respective laws would have not been the case if it was not for the attitudes and "silent approval" of many (but not all) occupational physicians. Laws defining the responsibilities of occupational medicine service units on one hand, and of employers on the other, are for many reasons infringed by both groups. CONCLUSIONS: The data analyses indicate that the Polish OHS is, to a large extent, not acceptable and should be replaced with another one founded on other assumptions and responsive to contemporary occupational health challenges. New provisions should be formulated on the basis of merit and guided by socially accepted norms. PMID- 26674169 TI - [Smoking at workplace - Legislation and health aspect of exposure to second-hand tobacco smoke]. AB - Tobacco smoke contains thousands of xenobiotics harmful to human health. Their irritant, toxic and carcinogenic potential has been well documented. Passive smoking or exposure to second-hand smoke (SHS) in public places, including workplace, poses major medical problems. Owing to this fact there is a strong need to raise workers' awareness of smoking-related hazards through educational programs and to develop and implement legislation aimed at eliminating SHS exposure. This paper presents a review of reports on passive exposure to tobacco smoke and its impact on human health and also a review of binding legal regulations regarding smoking at workplace in Poland. It has been proved that exposure to tobacco smoke during pregnancy may lead to, e.g., preterm delivery and low birth weight, sudden infant death syndrome, lung function impairment, asthma and acute respiratory illnesses in the future. Exposure to tobacco smoke, only in the adult age, is also considered as an independent risk factor of cardiovascular diseases, acute and chronic respiratory diseases and cancer. Raising public awareness of tobacco smoke harmfulness should be a top priority in the field of workers' health prevention. Occupational medicine physicians have regular contacts with occupationally active people who smoke. Thus, occupational health services have a unique opportunity to increase employees and employers' awareness of adverse health effects of smoking and their prevention. PMID- 26674170 TI - [Chemical analysis of wastewater as a new way of monitoring drugs and medicines consumption at workplace]. AB - The available information on the quality and frequency of illegal psychoactive substances used or medicines misused by workers, are often out of date at the time of its publication. This is due to the dynamic introduction of new synthetic drugs on the black market, changes in trends in the recreational use of medicines and the lack of readily available and reliable tests for fast identification. Strategy for detection of narcotic and non-medical psychoactive drugs use at workplace should embrace all possible sources of information. Classical sources of information on the use of psychoactive substances at the workplace include: statistical data (general information on trends and magnitude of drug and medicine addiction collected by the Polish National Police, the National Bureau for Drug Prevention and emergency medical services), surveys, psychomotor tests and qualitative and quantitative analyses of biological material. Of the new and promising methods, used throughout the world in recent years, chemical toxicological analysis of surface water and wastewater deserve special mention. An increasing interest in the study of urban waste water can significantly complement the source of knowledge about drug and medicine addiction using obtainable conventional methods. In recent years, a municipal wastewater analysis has become a new and very promising way of collecting updated information on the use of psychoactive substances and medicines. It seems that this kind of study may play an important role in the ongoing monitoring of drug and/or medicines use by selected groups of population (e.g., students, military, firemen, policemen, etc.). PMID- 26674171 TI - Cooperative reduction by Ln(2+) and Cp*(-) ions: synthesis and properties of Sm, Eu, and Yb complexes with 3,6-di-tert-butyl-o-benzoquinone. AB - The first examples of samarium, europium, and ytterbium complexes with 3,6-di tert-butyl-o-benzoquinone(3,6-dbbq) in the form of catecholate have been obtained by reactions of the quinone with the corresponding lanthanocenes, [LnCp2*(thf)n] (n = 1 or 2) in solution. In the course of the reactions lanthanide ions lose one or two Cp* ligands, which take part in reduction of a quinone molecule into a catecholate anion (dbcat, 2(-)). As a result of the reactions, Sm and Yb clearly yield dimeric complexes[(LnCp*)2(dbcat)2], where each Ln ion loses one Cp* ligand. Eu forms a trimeric complex [(EuCp*)-(Eu.thf)2(dbcat)3], in which one Eu ion is coordinated by one Cp* ligand, while two Eu ions have lost all Cp* ligands and are coordinated by THF molecules instead. Magnetic properties corroborate the assignment of oxidation states made on the basis of single-crystal X-ray diffraction: all the quinone ligands are present in the catecholate state; both Sm/Yb ions in the dimers are in the +3 oxidation state, whereas the Eu trimer contains two Eu(II) and one Eu(III) ions. Cyclovoltammetry studies show the presence of two reversible oxidation waves for all complexes, presumably concerned with the redox transitions of the dbcat ligands. PMID- 26674172 TI - The effect of extrusion on the functional components and in vitro lycopene bioaccessibility of tomato pulp added corn extrudates. AB - The effect of processing on functional ingredients and their in vitro bioaccessibility should be investigated to develop better food products. Tomato pulp was added as a functional ingredient to extrudates. The effects of extrusion on the functional properties of the extrudates and the in vitro bioaccessibility of lycopene were investigated. Two different temperature sets were applied during extrusion: 80 degrees C, 90 degrees C, 100 degrees C and 130 degrees C and 80 degrees C, 100 degrees C, 130 degrees C and 160 degrees C. Screw speed and feed rate were kept constant at 225 rpm and 36 +/- 1 g min(-1), respectively. The feed moisture content was adjusted to 30 +/- 1% by mixing the tomato pulp to the corn grit. Antioxidant activity and the total phenolic content decreased after the extrusion process. High performance liquid chromatography (HPLC) analysis indicated that the lycopene content decreased after the extrusion process when feed and extrudates were compared. In vitro bioaccessibility of lycopene for the extruded samples with 160 degrees C last zone treatment temperature was higher than the feed and extruded samples with 130 degrees C last zone treatment temperature. The results indicate that extrusion affects the food matrix and the release of functional components. PMID- 26674174 TI - Enhanced ELISA using a handheld pH meter and enzyme-coated microparticles for the portable, sensitive detection of proteins. AB - This work describes a general methodology for enhanced enzyme-linked immunosorbent assay (ELISA) that integrates enzyme-coated microparticle probes for robust yet highly efficient signal amplification and a handheld pH meter for a simple, portable, quantitative readout. Its utility is well demonstrated with the detection of the target protein with a 14-fold enhancement of sensitivity in comparison with the conventional optical ELISA. PMID- 26674173 TI - Viruses, Other Pathogenic Microorganisms and Esophageal Cancer. AB - BACKGROUND: Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. SUMMARY: Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. KEY MESSAGE: Among the above mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. PRACTICAL IMPLICATIONS: Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti infection measures to prevent EC. PMID- 26674175 TI - Silk Fibroin Aqueous-Based Adhesives Inspired by Mussel Adhesive Proteins. AB - Silk fibroin from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that end-cap a hydrophobic core consisting of repeating sequences of glycine, alanine, and serine residues. Taking inspiration from mussels that produce proteins rich in L-3,4 dihydroxyphenylalanine (DOPA) to adhere to a variety of organic and inorganic surfaces, the silk fibroin was functionalized with catechol groups. Silk fibroin was selected for its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and wide availability. The synthesis of catechol-functionalized silk fibroin polymers containing varying amounts of hydrophilic polyethylene glycol (PEG, 5000 g/mol) side chains was carried out to balance silk hydrophobicity with PEG hydrophilicity. The efficiency of the catechol functionalization reaction did not vary with PEG conjugation over the range studied, although tuning the amount of PEG conjugated was essential for aqueous solubility. Adhesive bonding and cell compatibility of the resulting materials were investigated, where it was found that incorporating as little as 6 wt % PEG prior to catechol functionalization resulted in complete aqueous solubility of the catechol conjugates and increased adhesive strength compared with silk lacking catechol functionalization. Furthermore, PEG-silk fibroin conjugates maintained their ability to form beta-sheet secondary structures, which can be exploited to reduce swelling. Human mesenchymal stem cells (hMSCs) proliferated on the silks, regardless of PEG and catechol conjugation. These materials represent a protein-based approach to catechol-based adhesives, which we envision may find applicability as biodegradable adhesives and sealants. PMID- 26674176 TI - Comparative Evaluation of Oral Health Knowledge, Practices and Attitude of Pregnant and Non-Pregnant Women, and Their Awareness Regarding Adverse Pregnancy Outcomes. AB - BACKGROUND: Adverse pregnancy outcomes are undesirable events occurring during pregnancy and childbirth in mother or child, such as Preterm Low Birth Weight (PLBW) and preeclampsia. There is growing evidence that periodontitis may be a risk factor for preterm birth even after adjusting for known risk factors. AIM: 1. To determine the knowledge and attitude of pregnant females about oral health. 2. To evaluate the oral hygiene practices of pregnant females. 3. To evaluate their awareness regarding effect of oral health on adverse pregnancy outcomes. 4. To assess whether there was any significant difference from their non pregnant counter parts. 5. To evaluate whether their awareness towards dental treatment had increased after conceiving. MATERIALS AND METHODS: 200 pregnant and 200 non pregnant women filled up a validated questionnaire which comprised of questions on personal data, oral hygiene knowledge, attitude, oral hygiene practices and their awareness regarding the correlation of oral health to adverse pregnancy outcomes. STATISTICAL ANALYSIS: Analyses were conducted using SPSS for Windows (version 15.0; SPSS Inc., Chicago, IL, USA). RESULTS: The results indicate no statistically significant differences in the variables assessed in both the groups, indicating that no further knowledge had been imparted to the women after they conceived. 96% women of both groups (p>0.05) had received no knowledge from the gynaecologist regarding the impact of oral health on pregnancy outcomes. 93.9% of pregnant women, and 89.5% of non pregnant women (p>0.05) did not go for routine dental check-ups. Only 3% of pregnant women were aware of oral health having a correlation with adverse pregnancy outcomes. CONCLUSION: In our study, pregnancy did little to change future attitudes to dental care. To provide better oral health care, more knowledge needs to be made available to the pregnant women and the medical community. PMID- 26674178 TI - A delay differential equation model of follicle waves in women. AB - This article presents a mathematical model for hormonal regulation of the menstrual cycle which predicts the occurrence of follicle waves in normally cycling women. Several follicles of ovulatory size that develop sequentially during one menstrual cycle are referred to as follicle waves. The model consists of 13 nonlinear, delay differential equations with 51 parameters. Model simulations exhibit a unique stable periodic cycle and this menstrual cycle accurately approximates blood levels of ovarian and pituitary hormones found in the biological literature. Numerical experiments illustrate that the number of follicle waves corresponds to the number of rises in pituitary follicle stimulating hormone. Modifications of the model equations result in simulations which predict the possibility of two ovulations at different times during the same menstrual cycle and, hence, the occurrence of dizygotic twins via a phenomenon referred to as superfecundation. Sensitive parameters are identified and bifurcations in model behaviour with respect to parameter changes are discussed. Studying follicle waves may be helpful for improving female fertility and for understanding some aspects of female reproductive ageing. PMID- 26674177 TI - Comparative Study between Monopolar Electrodes and Bipolar Electrodes in Hysteroscopic Surgery. AB - BACKGROUND: The hysteroscopic surgery has become a simple and safe technique, with the use of small hysteroscopes and bipolar energy with trained surgeons, which can prevent abortions and probably increase fertility. AIM: The study was conducted to evaluate the outcomes after hysteroscopic surgery by using uninopolar or bipolar electrodes. SETTING AND DESIGN: At the department of Obstetrics and Gynaecology, Qena university hospital and is a prospective non randomized clinical study. MATERIALS AND METHODS: One hundred fifty patients who included in this study were non randomly classified into two groups; one for hysteroscopic surgery by using bipolar electrode and the second group using unipolar electrode. Operative complications; bleeding, perforation, fluid over load and hyponatraemia were recorded. Also, operative time and hospital stay were included. RESULTS: There were no statistically significant differences between both groups in patient's characteristics, ultrasono-graphic findings, serum sodium levels before surgical interference, perforation and intraoperative bleeding. The fluid overload was significantly higher in unipolar group (p value= 0.03), postoperative hyponatraemia was significantly marked in unipolar group (p<0.05) and the changes of the levels of serum sodium in unipolar group in comparison to bipolar group were significantly different (p = 0.01). The mean operative time was significantly less in the bipolar group when compared to the unipolar group (p = 0.01) and the hospital stay was obviously less for patients of the bipolar group in comparison to unipolar group (p=0.04). CONCLUSION: Operative hysteroscopy using bipolar electrodes associated with significant decrease in hyponatraemia, operative time and postoperative hospital stay. So, it is safe and effective method when compared to using the unipolar electrodes. PMID- 26674179 TI - Modeling human development and disease in Xenopus. Preface. PMID- 26674180 TI - Right ventricular function assessment using tissue Doppler imaging and speckle tracking echocardiography. AB - Modern echocardiographic techniques, i.e. tissue Doppler imaging and speckle tracking echocardiography, allow for an assessment of global and regional right ventricular function. The right ventricular myocardial performance index and tricuspid annulus motion are used in the assessment of global right ventricular function, whereas duration of the cardiac cycle phases and myocardial velocities are used in the assessment of regional function. Strain and strain rate allow for an evaluation of both regional and global myocardial function. Literature reports provide data on the usefulness of these methods in patients with pressure and volume overload as well as with direct myocardial damage involving the right ventricle. In pulmonary hypertension, S' wave assessment may be used for therapeutic efficacy evaluation. Longitudinal strain reduction indicates an increased risk of vascular events, while an increased value of myocardial performance index is a predictor for a survival in pulmonary hypertension. A decreased S' wave velocity is associated with limited pulmonary vascular flow in patients with pulmonary embolism. In patients after atrial baffle repair for transposition of the great arteries, decreased longitudinal strain was an independent predictor for heart failure. A statistically significant decrease in both the S' wave as well as acceleration during isovolumic contraction were observed in arrhythmogenic right ventricular cardiomyopathy. S' wave and global right ventricular longitudinal strain values were lower in patients in the acute phase of myocardial infarction involving the right ventricle compared to the corresponding parameters in healthy individuals. In the case of tetralogy of Fallot correction, the evaluation of S' wave velocity may prove useful in identifying patients with reduced cardiac systolic reserve; a good correlation was also found between the global right ventricular longitudinal strain and right ventricular ejection fraction in MRI. PMID- 26674181 TI - Return to Play After Soleus Muscle Injuries. AB - BACKGROUND: Soleus muscle injuries are common in different sports disciplines. The time required for recovery is often difficult to predict, and reinjury is common. The length of recovery time might be influenced by different variables, such as the involved part of the muscle. HYPOTHESIS: Injuries in the central aponeurosis have a worse prognosis than injuries of the lateral or medial aponeurosis as well as myofascial injuries. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 61 high-level or professional athletes from several sports disciplines (soccer, tennis, track and field, basketball, triathlon, and field hockey) were reviewed prospectively to determine the recovery time for soleus muscle injuries. Clinical and magnetic resonance imaging evaluation was performed on 44 soleus muscle injuries. The association between the different characteristics of the 5 typical muscle sites, including the anterior and posterior myofascial and the lateral, central, and medial aponeurosis disruption, as well as the injury recovery time, were determined. Recovery time was correlated with age, sport, extent of edema, volume, cross sectional area, and retraction extension or gap. RESULTS: Of the 44 patients with muscle injuries who were analyzed, there were 32 (72.7%) strains affecting the myotendinous junction (MT) and 12 (23.7%) strains of the myofascial junction. There were 13 injuries involving the myotendinous medial (MTM), 7 affecting the MT central (MTC), 12 the MT lateral (MTL), 8 the myofascial anterior (MFA), and 4 the myofascial posterior (MFP). The median recovery time (+/-SD) for all injuries was 29.1 +/- 18.8 days. There were no statistically significant differences between the myotendinous and myofascial injuries regarding recovery time. The site with the worst prognosis was the MTC aponeurosis, with a mean recovery time of 44.3 +/- 23.0 days. The site with the best prognosis was the MTL, with a mean recovery time of 19.2 +/- 13.5 days (P < .05). There was a statistically significant correlation between recovery time and age (P < .001) and between recovery time and the extent of retraction (P < .05). CONCLUSION: Wide variation exists among the different types of soleus injuries and the corresponding recovery time for return to the same level of competitive sports. Injuries in the central aponeurosis have a significantly longer recovery time than do injuries in the lateral and medial aponeurosis and myofascial sites. PMID- 26674182 TI - Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy. AB - INTRODUCTION: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments. AREAS COVERED: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME. A literature search was performed using the following terms: anti VEGF, DME, aflibercept, bevacizumab, ranibizumab, refractory macular edema, and VEGF. EXPERT OPINION: Focal extrafoveal DME may be treated first-line with laser. In patients with center-involving DME and only mild vision loss, consider starting treatment with bevacizumab, especially when cost is an issue, whereas aflibercept may be considered more strongly in patients with moderate visual loss or worse. There are no standard protocols that define 'treatment failure,' but several studies have reported that switching from bevacizumab to either ranibizumab or aflibercept will result in further reduction of CSFT and improvement in BCVA. Further study with prospective randomized trials is warranted to validate these findings. Switching to intravitreal corticosteroids may be of particular benefit to pseudophakic patients. Anti-VEGF combination with sustained-release corticosteroids also appears promising for refractory DME. PMID- 26674183 TI - Analytical Model for Estimating Terrestrial Cosmic Ray Fluxes Nearly Anytime and Anywhere in the World: Extension of PARMA/EXPACS. AB - By extending our previously established model, here we present a new model called "PHITS-based Analytical Radiation Model in the Atmosphere (PARMA) version 3.0," which can instantaneously estimate terrestrial cosmic ray fluxes of neutrons, protons, ions with charge up to 28 (Ni), muons, electrons, positrons, and photons nearly anytime and anywhere in the Earth's atmosphere. The model comprises numerous analytical functions with parameters whose numerical values were fitted to reproduce the results of the extensive air shower (EAS) simulation performed by Particle and Heavy Ion Transport code System (PHITS). The accuracy of the EAS simulation was well verified using various experimental data, while that of PARMA3.0 was confirmed by the high R2 values of the fit. The models to be used for estimating radiation doses due to cosmic ray exposure, cosmic ray induced ionization rates, and count rates of neutron monitors were validated by investigating their capability to reproduce those quantities measured under various conditions. PARMA3.0 is available freely and is easy to use, as implemented in an open-access software program EXcel-based Program for Calculating Atmospheric Cosmic ray Spectrum (EXPACS). Because of these features, the new version of PARMA/EXPACS can be an important tool in various research fields such as geosciences, cosmic ray physics, and radiation research. PMID- 26674184 TI - Nature of low-frequency noise in homogeneous semiconductors. AB - This report deals with a 1/f noise in homogeneous classical semiconductor samples on the base of silicon. We perform detail calculations of resistance fluctuations of the silicon sample due to both a) the charge carrier number changes due to their capture-emission processes, and b) due to screening effect of those negative charged centers, and show that proportionality of noise level to square mobility appears as a presentation parameter, but not due to mobility fluctuations. The obtained calculation results explain well the observed experimental results of 1/f noise in Si, Ge, GaAs and exclude the mobility fluctuations as the nature of 1/f noise in these materials and their devices. It is also shown how from the experimental 1/f noise results to find the effective number of defects responsible for this noise in the measured frequency range. PMID- 26674185 TI - The Shifting Climate Portfolio of the Greater Yellowstone Area. AB - Knowledge of climatic variability at small spatial extents (< 50 km) is needed to assess vulnerabilities of biological reserves to climate change. We used empirical and modeled weather station data to test if climate change has increased the synchrony of surface air temperatures among 50 sites within the Greater Yellowstone Area (GYA) of the interior western United States. This important biological reserve is the largest protected area in the Lower 48 states and provides critical habitat for some of the world's most iconic wildlife. We focused our analyses on temporal shifts and shape changes in the annual distributions of seasonal minimum and maximum air temperatures among valley bottom and higher elevation sites from 1948-2012. We documented consistent patterns of warming since 1948 at all 50 sites, with the most pronounced changes occurring during the Winter and Summer when minimum and maximum temperature distributions increased. These shifts indicate more hot temperatures and less cold temperatures would be expected across the GYA. Though the shifting statistical distributions indicate warming, little change in the shape of the temperature distributions across sites since 1948 suggest the GYA has maintained a diverse portfolio of temperatures within a year. Spatial heterogeneity in temperatures is likely maintained by the GYA's physiographic complexity and its large size, which encompasses multiple climate zones that respond differently to synoptic drivers. Having a diverse portfolio of temperatures may help biological reserves spread the extinction risk posed by climate change. PMID- 26674186 TI - Nonsteroidal antiinflammatory drug induced acute granulomatous interstitial nephritis. AB - BACKGROUND: Acute interstitial nephritis is a common cause of acute kidney injury (AKI). The granulomatous inflammation is rarely but often manifests as a form of a granulomatous interstitial nephritis (GIN) in the kidney. Acute granulomatous interstitial nephritis is mainly associated with drugs, infection and autoimmune diseases. CASE PRESENTATION: A 44-year-old-male visited our out-patient department with symptoms of nausea, vomiting, and general weakness that had developed over the previous 2 weeks. He had history of medication, nonsteroidal anti-inflammatory drugs. On admission to the general ward, his serum creatinine level was markedly elevated. GIN was confirmed by renal biopsy and 30 mg of corticosteroid per day was immediately initiated. Subsequently, his serum creatinine level and uremic symptoms dramatically decreased. CONCLUSION: Acute granulomatous interstitial nephritis is a rare but important disease on AKI. As long as we can carefully exclude infectious diseases as the cause of granulomatous lesion, acute granulomatous interstitial nephritis can be treated with steroid regardless of the etiologies. Since there is no proven treatment for the GIN yet, we can carefully suggest that moderate to high dosage corticosteroid can be helpful for prognosis in case of acute granulomatous interstitial nephritis of patients with AKI. PMID- 26674187 TI - A randomized trial testing the efficacy of modifications to the nutrition facts table on comprehension and use of nutrition information by adolescents and young adults in Canada. AB - INTRODUCTION: Given the proposed changes to nutrition labelling in Canada and the dearth of research examining comprehension and use of nutrition facts tables (NFts) by adolescents and young adults, our objective was to experimentally test the efficacy of modifications to NFts on young Canadians' ability to interpret, compare and mathematically manipulate nutrition information in NFts on prepackaged food. METHODS: An online survey was conducted among 2010 Canadians aged 16 to 24 years drawn from a consumer sample. Participants were randomized to view two NFts according to one of six experimental conditions, using a between groups 2 x 3 factorial design: serving size (current NFt vs. standardized serving sizes across similar products) x percent daily value (% DV) (current NFt vs. "low/med/high" descriptors vs. colour coding). The survey included seven performance tasks requiring participants to interpret, compare and mathematically manipulate nutrition information on NFts. Separate modified Poisson regression models were conducted for each of the three outcomes. RESULTS: The ability to compare two similar products was significantly enhanced in NFt conditions that included standardized serving-sizes (p <= .001 for all). Adding descriptors or colour coding of % DV next to calories and nutrients on NFts significantly improved participants' ability to correctly interpret % DV information (p <= .001 for all). Providing both standardized serving-sizes and descriptors of % DV had a modest effect on participants' ability to mathematically manipulate nutrition information to calculate the nutrient content of multiple servings of a product (relative ratio = 1.19; 95% confidence limit: 1.04-1.37). CONCLUSION: Standardizing serving-sizes and adding interpretive % DV information on NFts improved young Canadians' comprehension and use of nutrition information. Some caution should be exercised in generalizing these findings to all Canadian youth due to the sampling issues associated with the study population. Further research is needed to replicate this study in a more heterogeneous sample in Canada and across a range of food products and categories. PMID- 26674189 TI - Chronic Disease and Injury Indicator Framework: Quick Stats, 2015 Edition. PMID- 26674188 TI - Trends in prevalence, incidence and mortality of diagnosed and silent coronary heart disease in Quebec. AB - INTRODUCTION: Of all cardiovascular causes of mortality, coronary heart disease (CHD) remains the leading cause of death. Our objectives were to establish trends in the prevalence and incidence of CHD in the province of Quebec, and to determine the proportion of CHD mortality that had no previous CHD diagnosis. METHODS: Trends in prevalence, incidence and mortality were examined with a population-based study using the Quebec Integrated Chronic Disease Surveillance System, which links several health administrative databases. Data are presented using two case definitions for Quebecers aged 20 years and over: 1) a validated definition, and 2) CHD causes of death codes added to estimate the proportion of deaths that occurred without any previous CHD diagnosis as a proxy for sudden cardiac death (SCD). RESULTS: In 2012/2013, the crude prevalence of CHD was 9.4% with the first definition (593 000 people). Between 2000/2001 and 2012/2013, the age-standardized prevalence increased by 14%, although it has been decreasing slightly since 2009/2010. Age-standardized incidence and mortality rates decreased by 46% and 26% respectively, and represented a crude rate of 6.9 per 1000 and 5.2% in 2012/2013. The proportion identified only by CHD mortality, our SCD proxy, was only significant for the incident cases (0.38 per 1000 in 2009/2010) and declined over the study period. CONCLUSION: The prevalence of CHD has tended to decrease in recent years, and incidence and mortality have been declining in Quebec. Most CHD mortality occurs in previously diagnosed patients and only a small proportion of incident cases were not previously identified. PMID- 26674190 TI - Type 1 Retinopathy of Prematurity and Its Laser Treatment of Large Preterm Infants in East China. AB - PURPOSE: To describe Type 1 retinopathy of prematurity (ROP) and its laser treatment outcomes in premature infants with birth weight > 1250 g in Eastern China. METHODS: A retrospective review of 3175 ROP records was conducted at Shanghai Eye & ENT Hospital of Fudan University. The records were collected at the ROP clinic from 2006 to 2014, including their demographic and medical information such as gestational age, birth weight, supplemental oxygen therapy, systemic complications, ROP stage, location, presence of plus disease. All infants were examined by RetCam fundus camera. Those with Type 1 ROP were also examined by indirect ophthalmoscope before undergoing transpupillary laser treatment. RESULTS: A total of 12 infants (24 eyes) with Type 1 ROP and birth weight > 1250 g were enrolled. All infants enrolled had plus disease and ROP in zone II retina. Specifically, 16 eyes (67%) had stage 2 ROP. 8 eyes (33%) had stage 3 ROP. ROP regressed in 23 eyes (96%) following laser treatment. Partial retinal detachment developed in one eye (4%). No severe involution sequelaes or laser-related complications were recorded. Mean follow-up was 30+/-6 weeks. CONCLUSION: Type 1 ROP may occur in large premature infants who have undergone supplemental oxygen therapy. This Type 1 ROP is mainly located in zone II retina. Laser treatment is a safe and effective intervention for these infants. PMID- 26674191 TI - Unpicking the signal thread of the sector web spider Zygiella x-notata. AB - Remote sensing allows an animal to extend its morphology with appropriate conductive materials and sensors providing environmental feedback from spatially removed locations. For example, the sector web spider Zygiella x-notata uses a specialized thread as both a structural bridge and signal transmitter to monitor web vibrations from its retreat at the web perimeter. To unravel this model multifunctional system, we investigated Zygiella's signal thread structure with a range of techniques, including tensile testing, laser vibrometry, electron microscopy and behavioural analysis. We found that signal threads varied significantly in the number of filaments; a result of the spider adding a lifeline each time it runs along the bridge. Our mechanical property analysis suggests that while the structure varies, its normalized load does not. We propose that the signal thread represents a complex and fully integrated multifunctional structure where filaments can be added, thus increasing absolute load-bearing capacity while maintaining signal fidelity. We conclude that such structures may serve as inspiration for remote sensing design strategies. PMID- 26674192 TI - Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement. AB - Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro. Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo. It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a 'peel-back' leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 +/- 2.04% versus circular = 11.77 +/- 1.61%, p = 0.0014, hypertension: eccentric = 15.07 +/- 1.13% versus circular = 13.56 +/- 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve. PMID- 26674193 TI - Maintenance of phenotypic diversity within a set of virulence encoding genes of the malaria parasite Plasmodium falciparum. AB - Infection by the human malaria parasite Plasmodium falciparum results in a broad spectrum of clinical outcomes, ranging from severe and potentially life threatening malaria to asymptomatic carriage. In a process of naturally acquired immunity, individuals living in malaria-endemic regions build up a level of clinical protection, which attenuates infection severity in an exposure-dependent manner. Underlying this shift in the immunoepidemiology as well as the observed range in malaria pathogenesis is the var multigene family and the phenotypic diversity embedded within. The var gene-encoded surface proteins Plasmodium falciparum erythrocyte membrane protein 1 mediate variant-specific binding of infected red blood cells to a diverse set of host receptors that has been linked to specific disease manifestations, including cerebral and pregnancy-associated malaria. Here, we show that cross-reactive immune responses, which minimize the within-host benefit of each additionally expressed gene during infection, can cause selection for maximum phenotypic diversity at the genome level. We further show that differential functional constraints on protein diversification stably maintain uneven ratios between phenotypic groups, in line with empirical observation. Our results thus suggest that the maintenance of phenotypic diversity within P. falciparum is driven by an evolutionary trade-off that optimizes between within-host parasite fitness and between-host selection pressure. PMID- 26674194 TI - Impacts of feeding less food-competing feedstuffs to livestock on global food system sustainability. AB - Increasing efficiency in livestock production and reducing the share of animal products in human consumption are two strategies to curb the adverse environmental impacts of the livestock sector. Here, we explore the room for sustainable livestock production by modelling the impacts and constraints of a third strategy in which livestock feed components that compete with direct human food crop production are reduced. Thus, in the outmost scenario, animals are fed only from grassland and by-products from food production. We show that this strategy could provide sufficient food (equal amounts of human-digestible energy and a similar protein/calorie ratio as in the reference scenario for 2050) and reduce environmental impacts compared with the reference scenario (in the most extreme case of zero human-edible concentrate feed: greenhouse gas emissions 18%; arable land occupation -26%, N-surplus -46%; P-surplus -40%; non-renewable energy use -36%, pesticide use intensity -22%, freshwater use -21%, soil erosion potential -12%). These results occur despite the fact that environmental efficiency of livestock production is reduced compared with the reference scenario, which is the consequence of the grassland-based feed for ruminants and the less optimal feeding rations based on by-products for non-ruminants. This apparent contradiction results from considerable reductions of animal products in human diets (protein intake per capita from livestock products reduced by 71%). We show that such a strategy focusing on feed components which do not compete with direct human food consumption offers a viable complement to strategies focusing on increased efficiency in production or reduced shares of animal products in consumption. PMID- 26674195 TI - A generative inference framework for analysing patterns of cultural change in sparse population data with evidence for fashion trends in LBK culture. AB - Cultural change can be quantified by temporal changes in frequency of different cultural artefacts and it is a central question to identify what underlying cultural transmission processes could have caused the observed frequency changes. Observed changes, however, often describe the dynamics in samples of the population of artefacts, whereas transmission processes act on the whole population. Here we develop a modelling framework aimed at addressing this inference problem. To do so, we firstly generate population structures from which the observed sample could have been drawn randomly and then determine theoretical samples at a later time t2 produced under the assumption that changes in frequencies are caused by a specific transmission process. Thereby we also account for the potential effect of time-averaging processes in the generation of the observed sample. Subsequent statistical comparisons (e.g. using Bayesian inference) of the theoretical and observed samples at t2 can establish which processes could have produced the observed frequency data. In this way, we infer underlying transmission processes directly from available data without any equilibrium assumption. We apply this framework to a dataset describing pottery from settlements of some of the first farmers in Europe (the LBK culture) and conclude that the observed frequency dynamic of different types of decorated pottery is consistent with age-dependent selection, a preference for 'young' pottery types which is potentially indicative of fashion trends. PMID- 26674196 TI - Design of a bistable switch to control cellular uptake. AB - Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation-repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on-off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. PMID- 26674197 TI - Older people coping with low mood: a qualitative study. AB - BACKGROUND: To gain new insight into support for older people with low mood, the perceptions, strategies, and needs of older people with depressive symptoms were explored. METHODS: Two in-depth interviews were held with 38 participants (aged >=77 years) who screened positive for depressive symptoms in general practice. To investigate the influence of the presence of complex health problems, 19 persons with and 19 without complex problems were included. Complex problems were defined as a combination of functional, somatic, psychological or social problems. RESULTS: All participants used several cognitive, social or practical coping strategies. Four patterns emerged: mastery, acceptance, ambivalence, and need for support. Most participants felt they could deal with their feelings sufficiently, whereas a few participants with complex problems expressed a need for professional support. Some participants, especially those with complex problems, were ambivalent about possible interventions mainly because they feared putting their fragile balance at risk due to changes instigated by an intervention. CONCLUSION: Most older participants with depressive symptoms perceived their coping strategies to be sufficient. The general practitioners (GPs) can support self-management by talking about the (effectiveness of) personal coping strategies, elaborating on perceptions of risks, providing information, and discussing alternative options with older persons. PMID- 26674198 TI - Polymer-based Drug Delivery Systems Applied to Insects Repellents Devices: A Review. AB - Insects-borne diseases constitute a public health concern. Since there is no vaccine or curative treatment for many of these diseases, individual protection is the main approach to prevent them. Nowadays, the search for replacing synthetic molecules for insect repellents from natural sources, such as essential oils, is increasing. However, most of them present low efficiency compared to synthetic repellents. Therefore, decreasing skin permeation of synthetic repellents or yet, increasing effectiveness of natural repellents are challenges that must be overcome during the development of novel insect repellent formulations. In this context, polymer-based formulations allow entrapping active ingredients and provide release control. Encapsulation into polymeric micro/nanocapsules, cyclodextrins, polymeric micelles or hydrogels constitutes an approach to modify physicochemical properties of encapsulated molecules. Such techniques, applied in topical formulations, fabrics modification for personal protection, or food packaging have proved to be more effective in increasing repellency time and also in reducing drug dermal absorption, improving safety profiles of these products. In this work, the main synthetic and natural insect repellents are described as well as their polymeric carrier systems and their potential applications. PMID- 26674199 TI - PEGylated Biodegradable Polyesters for PGSS Microparticles Formulation: Processability, Physical and Release Properties. AB - BACKGROUND: Particles from Gas Saturated Solution (PGSS) is an emergent method that employs supercritical carbon dioxide (scCO2) to produce microparticles. It is suitable for encapsulating biologically active compounds including therapeutic peptides and proteins. Poly(lactide acid) (PLA) and/or poly(lactic-coglycolic acid) (PLGA) are the most commonly used materials in PGSS, due to their good processability in scCO2. Previous studies demonstrated that the properties of the microparticles can be modulated by adding polyethylene glycol (PEG) or tri-block PEGylated copolymers. OBJECTIVE: In the present work, the effect of the addition of biodegradable PEGylated di-block copolymers on the physical properties and drug release performance of microparticles prepared by PGSS technique was evaluated. METHOD: mPEG5kDa-P(L)LA and mPEG5kDa-P(L)LGA with similar molecular weights were synthesized and their behaviour, when exposed to supercritical CO2, was investigated. Different microparticle formulations, composed of a high (81%) or low (9%) percentage of the synthesized copolymers were prepared and compared in terms of particle size distribution, morphology, yield and protein release. Drug release studies were performed using bovine serum albumin (BSA) as a model protein. RESULTS: PEGylated copolymers showed good processability in PGSS without significant changes to the physical properties of the microparticles. However, the addition of PEG exerted a modulating effect on the microparticle drug dissolution behaviour, increasing the rate of BSA release as a function of its content in the formulation. CONCLUSION: This study demonstrated the feasibility of producing microparticles by using PEGylated di-block copolymers through a PGSS technique at mild operating conditions (low operating pressure and temperature). PMID- 26674200 TI - Improving Cycling Performance: Transcranial Direct Current Stimulation Increases Time to Exhaustion in Cycling. AB - The central nervous system seems to have an important role in fatigue and exercise tolerance. Novel noninvasive techniques of neuromodulation can provide insights on the relationship between brain function and exercise performance. The purpose of this study was to determine the effects of transcranial direct current stimulation (tDCS) on physical performance and physiological and perceptual variables with regard to fatigue and exercise tolerance. Eleven physically active subjects participated in an incremental test on a cycle simulator to define peak power output. During 3 visits, the subjects experienced 3 stimulation conditions (anodal, cathodal, or sham tDCS-with an interval of at least 48 h between conditions) in a randomized, counterbalanced order to measure the effects of tDCS on time to exhaustion at 80% of peak power. Stimulation was administered before each test over 13 min at a current intensity of 2.0 mA. In each session, the Brunel Mood State questionnaire was given twice: after stimulation and after the time-to-exhaustion test. Further, during the tests, the electromyographic activity of the vastus lateralis and rectus femoris muscles, perceived exertion, and heart rate were recorded. RM-ANOVA showed that the subjects performed better during anodal primary motor cortex stimulation (491 +/- 100 s) compared with cathodal stimulation (443 +/- 11 s) and sham (407 +/- 69 s). No significant difference was observed between the cathodal and sham conditions. The effect sizes confirmed the greater effect of anodal M1 tDCS (anodal x cathodal = 0.47; anodal x sham = 0.77; and cathodal x sham = 0.29). Magnitude-based inference suggested the anodal condition to be positive versus the cathodal and sham conditions. There were no differences among the three stimulation conditions in RPE (p = 0.07) or heart rate (p = 0.73). However, as hypothesized, RM- ANOVA revealed a main effect of time for the two variables (RPE and HR: p < 0.001). EMG activity also did not differ during the test accross the different conditions. We conclude that anodal tDCS increases exercise tolerance in a cycling-based, constant-load exercise test, performed at 80% of peak power. Performance was enhanced in the absence of changes in physiological and perceptual variables. PMID- 26674201 TI - Virgibacillus flavescens sp. nov., isolated from marine sediment. AB - A Gram-stain-variable, rod-shaped, motile bacterial strain, designated S1-20T, was isolated from marine sediment of the Yellow Sea in China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S1-20T was related to the genus Virgibacillus and had highest 16S rRNA gene sequence similarities with the type strains of Virgibacillus necropolis (98.1 %), Virgibacillus arcticus (97.7 %) and Virgibacillus carmonensis (97.3 %). The predominant cellular fatty acids of strain S1-20T were anteiso-C15 : 0 and anteiso-C17 : 0. The main menaquinone was MK-7. The genomic DNA G+C content of strain S1-20T was 38.3 mol%. The polar lipids profile contained diphosphatidylglycerol, phosphatidylglycerol, five unidentified phospholipids, one unknown aminophospholipid and an aminolipid. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain S1-20T is a representative of a novel species of the genus Virgibacillus, for which the name Virgibacillus flavescens sp. nov. is proposed. The type strain is S1-20T ( = LMG 28381T = DSM 29015T). PMID- 26674202 TI - Retrospective observation of mental disorders during postpartum period: Results from the Singapore mental health study. AB - BACKGROUND: The perinatal period has been identified as a period of vulnerability for various disorders (particularly anxiety and depressive disorders), which have been associated with negative outcomes for both mother and infant. The current study utilized data from the Singapore Mental Health Study (SMHS) to examine the temporal relationship between mental disorders and the perinatal period, as well as associated risk factors. METHODS: Life table estimation method was used to derive the estimated hazard rate for any mood or anxiety disorders following pregnancy. Multivariate logistic regression was used to examine the association between socio-demographic factors and onset of mental disorders after the first pregnancy. RESULTS: Among women with children (n = 2278), 1.5 % were found to have an onset of any mental disorder (i.e., mood disorders, anxiety disorders, alcohol use disorders), within 2 years after pregnancy. A peak in hazard rate was noted at approximately 1 year following pregnancy for anxiety disorders but not mood disorders. Women who were married, employed and physically healthy were less likely to have had developed any mental disorder. CONCLUSIONS: The prevalence of mental disorders during pregnancy and postpartum was found to be low among women with children in our community sample, with increased vulnerability following delivery. The results offer some insight into the occurrence of mental disorders during the perinatal period among women in Singapore. PMID- 26674204 TI - Early Neurodegeneration of the Inner Retinal Layers in Type 1 Diabetes Mellitus. AB - PURPOSE: This study explores retinal structural changes in type 1 diabetes without clinically diagnosed diabetic retinopathy (DR). METHODS: Peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell complex (GCC) thickness, and macular thickness (MT) were measured in 90 type 1 diabetic patients by using spectral domain optical coherence tomography. The values were compared with 100 sex- and age-matched healthy controls. The independent t test was used to assess differences in the mean age, mean diabetic and ocular parameters, and the thickness values between the diabetic and control groups. Multiple linear regression analysis was performed to investigate the correlation between the thickness values and diabetic and ocular parameters. RESULTS: Whole RNFL, the superior and inferior quadrants, and the superior half of the peripapillary RNFL thicknesses were significantly thinner in diabetic patients compared with controls (p < 0.05). GCC thicknesses in the average macular, outer temporal superior and outer temporal inferior sectors were significantly thinner in diabetic patients (p < 0.05). Central and average MTs were similar in both groups (p > 0.05). There were significant negative correlations of the duration of type 1 diabetes with the inner nasal MT, inner temporal superior GCC thickness, inner nasal inferior GCC thickness, and outer nasal superior GCC thickness (p < 0.05). Similarly, there were significant negative correlations of the level of HbA1c with the whole-RNFL thickness, superior-half-RNFL thickness, and superior-quadrant-RNFL thickness (p < 0.05). CONCLUSIONS: Type 1 diabetic patients without clinically diagnosed DR had neurodegeneration in the inner retinal layers compared with healthy controls. PMID- 26674203 TI - Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy. AB - Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes. PMID- 26674206 TI - Synthesis and Three-Dimensional Magnetic Field Mapping of Co2FeGa Heusler Nanowires at 5 nm Resolution. AB - We present the synthesis of Co2FeGa Heusler nanowires and the results of our investigations on their three-dimensional (3D) electric and magnetic internal and external fields mapped by electron holographic tomography (EHT). These fields will be of great importance in next-generation nanomagnets integrated in spintronics and memory devices. The Co2FeGa nanowires with a L21 ordered structure are prepared by a SBA-15 silica-assisted method. The magnetic dipole like stray fields of several Co2FeGa nanowires are revealed by holographically reconstructed phase images. Based on the measured magnetic phase shifts of an individual nanowire and its 3D reconstruction using EHT, we obtain an internal magnetic induction with a magnitude of 1.15 T and a nonmagnetic surface layer of 10 nm thickness. Furthermore, we also reconstruct the 3D distribution of the electrostatic potential of the same nanowire. PMID- 26674205 TI - Resveratrol elicits anti-colorectal cancer effect by activating miR-34c-KITLG in vitro and in vivo. AB - BACKGROUND: Silence of the tumor suppressor miR-34c is implicated in the development of colorectal cancer (CRC). For the past few years, Resveratrol (Res) has been introduced to oncotherapies alone or with traditional chemotherapeutic drugs. However, the study of molecular mechanism involved in the anti-CRC effect of Res is still ongoing. METHODS: The anti-CRC effect of Res alone or with Oxaliplatin (Oxa) was determined by cell viability assay, soft agar colony formation assay, flow cytometry and real-time cellular analyzer in HT-29 (p53+) and HCT-116 (p53-) CRC cell lines. Expressions of miR-34c and its targets were detected by qPCR and/or western blot. To evaluate the role of miR-34c in anti-CRC effect by Res alone or with Oxa, miR-34c was up or down-regulated by lentiviral mediation or specific inhibitor, respectively. To investigate how miR-34c was increased by Res, the methylation status of miR-34c promoter was detected by MSP. The tumor bearing mouse model was established by subcutaneous injection of HCT 116 cells to assess anti-CRC effect of Res alone or with Oxa in vivo. IL-6 and TNF-alpha in xenografts were detected by ELISA. RESULTS: Res inhibited cell viability, proliferation, migration and invasion as well as promoted apoptosis both in HT-29 and HCT-116 CRC cells. The anti-CRC effect of Res was partially but specifically through up-regulating miR-34c which further knocked down its target KITLG; and the effect was enhanced in the presence of p53 probably through inactivating PI3K/Akt pathway. Besides, Res sensitized CRC cells to Oxa in a miR 34c dependent manner. The xenograft experiments showed that exposure to Res or Oxa suppressed tumor growth; and the efficacy was evidently augmented by the co treatment of Res and Oxa. Likewise, miR-34c level was elevated in xenografts of Res-treated mice while the KITLG was decreased. Finally, Res clearly reduced IL-6 in xenografts. CONCLUSION: Res suppressed CRC by specifically activating miR-34c KITLG in vitro and in vivo; and the effect was strengthened in the presence of p53. Besides, Res exerted a synergistic effect with Oxa in a miR-34c dependent manner. We also suggested that Res-increased miR-34c could interfere IL-6 triggered CRC progression. PMID- 26674207 TI - Histomorphological Features of Intestinal Atresia and its Clinical Correlation. AB - INTRODUCTION: Intestinal atresia accounts for approximately one third of all cases of neonatal intestinal obstruction. There is controversy regarding pathogenesis of congenital atresia and stenosis of small bowel. Studies regarding clinical manifestations and specific histopathological features of neonatal intestinal atresia are scarce in Indian literature. AIM: To understand the histomorphological features and thus suggest pathophysiology of cases with Intestinal Atresia. MATERIALS AND METHODS: Out of 147 cases, of intestinal obstruction in newborn studied over a period of 5 years, 39 cases of intestinal atresia were found. Their histomorphological details with clinical manifestations were studied. RESULTS: Type II was the commonest type of atresia. Associated anomalies noted were gastroschisis, volvulus, anal stenosis, microcolon, annular pancreas, meconium cyst and duplication cyst. Histological changes observed were ulceration, flattening, abnormal villous configuration, luminal obliteration, narrowing, haemangiomatous proliferation of blood vessels, fibrosis, haemorrhage, calcification, and mesenchymal condensation around the blood vessels. Gangrene and perforation has also noted in some cases. CONCLUSION: An intrauterine intestinal ischemia due to vascular pathology followed by resorption of the bowel is the possible explanation for the development of intestinal atresia. PMID- 26674208 TI - Quantitative Activity Measurements of Brown Adipose Tissue at 7 T Magnetic Resonance Imaging After Application of Triglyceride-Rich Lipoprotein 59Fe Superparamagnetic Iron Oxide Nanoparticle: Intravenous Versus Intraperitoneal Approach. AB - OBJECTIVES: The aim of this study was to determine metabolic activity of brown adipose tissue (BAT) with in vivo magnetic resonance imaging (MRI) after intravenous (IV) and intraperitoneal (IP) injection of radioactively labeled superparamagnetic iron oxide nanoparticles (SPIOs) embedded into a lipoprotein layer. MATERIALS AND METHODS: Fe-labeled SPIOs were either polymer-coated or embedded into the lipid core of triglyceride-rich lipoproteins (TRL-Fe-SPIOs). First biodistribution and blood half time analysis in thermoneutral mice after IP injection of either TRL-Fe-SPIOs or polymer-coated Fe-SPIOs (n = 3) were performed. In the next step, cold-exposed (24 hours), BAT-activated mice (n = 10), and control thermoneutral mice (n = 10) were starved for 4 hours before IP (n = 10) or IV (n = 10) injection of TRL-Fe-SPIOs. In vivo MRI was performed before and 24 hours after the application of the particles at a 7 T small animal MRI scanner using a T2*-weighted multiecho gradient echo sequence. R2* and DeltaR2* were estimated in the liver, BAT, and muscle. The biodistribution of polymer-coated Fe-SPIOs and TRL-Fe-SPIOs was analyzed ex vivo using a sensitive, large-volume Hamburg whole-body radioactive counter. The amount of Fe-SPIOs in the liver, BAT, and muscle was correlated with the MRI measurements using the Pearson correlation coefficient. Tissue uptake of Fe-SPIOs was confirmed by histological and transmission electron microscopy analyses. RESULTS: Triglyceride rich lipoprotein Fe-SPIOs exhibited a higher blood concentration after IP injection (10.1% +/- 0.91% after 24 hours) and a greater [INCREMENT]R2* in the liver (103 +/- 5.0 s), while polymer-coated SPIOs did not increase substantially in the blood stream (0.19% +/- 0.01% after 24 hours; P < 0.001) and the liver (57 +/- 4.08 s; P < 0.001). In BAT activity studies, significantly higher uptake of TRL-Fe-SPIOs was detected in the BAT of cold-exposed mice, with [INCREMENT]R2* of 107 +/- 5.5 s after IV application (control mice: [INCREMENT]R2* of 22 +/- 5.8 s; P < 0.001) and 45 +/- 5.5 s after IP application (control mice: [INCREMENT]R2* of 11 +/- 2.9 s; P < 0.01). Fe radioactivity measurements and [INCREMENT]R2* values correlated strongly in BAT (r > 0.85; P < 0.001) and liver tissue (r > 0.85; P < 0.001). Histological and transmission electron microscopy analyses confirmed the uptake of TRL-Fe-SPIOs within the liver and BAT for both application approaches. CONCLUSIONS: Triglyceride-rich lipoprotein-embedded SPIOs were able to escape the abdominal cavity barrier, whereas polymer-coated SPIOs did not increase substantially in the blood stream. Brown adipose tissue activity can be determined via MRI using TRL-Fe-SPIOs. The quantification of [INCREMENT]R2* using TRL-Fe-SPIOs is feasible and may serve as a noninvasive tool for the quantitative estimation of BAT activity. PMID- 26674209 TI - Evaluation of Variable Density and Data-Driven K-Space Undersampling for Compressed Sensing Magnetic Resonance Imaging. AB - OBJECTIVES: The aim of this study was to investigate the influence of variable density and data-driven k-space undersampling patterns on reconstruction quality for compressed sensing (CS) magnetic resonance imaging to provide recommendations on how to avoid suboptimal CS reconstructions. MATERIALS AND METHODS: First, we investigated the influence of randomness and sampling density on the reconstruction quality when using random variable density and variable density Poisson disk undersampling. Compressed sensing reconstructions on 1 knee and 2 brain data sets were compared with fully sampled data sets and reconstruction errors were measured. Sampling coherence was evaluated on the undersampling patterns to investigate whether there was a relation between this coherence measure and reconstruction error.Second, we investigated whether data-driven undersampling methods could improve reconstruction quality when 1 or more fully sampled scans are available as a training set. We implemented 3 different data driven undersampling methods: (1) Monte Carlo optimization of variable density and variable density Poisson disk undersampling, (2) calculating sampling probabilities directly from the k-space power spectra of the training data, and (3) iterative design of undersampling patterns based on CS reconstruction errors in k-space.Two cross-validation experiments were set up using retrospective undersampling to evaluate the 3 data-driven methods and the influence of the size of the training set. Furthermore, in an experiment that included prospective under sampling, we show the practical applicability of 2 of the data-driven methods. Compressed sensing reconstruction quality was measured with both the normalized root-mean-square error metric and the mean structural similarity index measure. RESULTS: Different optimal variable sampling densities were found for each of the data sets, showing that the optimal sampling density is data dependent. Choosing a sampling density other than the optimal density decreased reconstruction quality. These results suggest that choosing a sampling density without having any reference scans is likely suboptimal. Furthermore, no meaningful correlation was found between sampling coherence and reconstruction error.For the data-driven methods, the iterative method yielded statistically significantly higher reconstruction quality in both retrospective and prospective experiments. In retrospective experiments, the power spectrum method yielded a reconstruction quality that was comparable with the data-driven variable density method. The size of the training set had only a minor influence on the reconstruction quality. CONCLUSIONS: Data-driven undersampling methods can be used to avoid suboptimal reconstruction quality in CS magnetic resonance imaging, provided that at least 1 fully sampled scan is available to train the data-driven method. The iterative design method resulted in the highest reconstruction quality. PMID- 26674210 TI - Well-Known Mediators of Selective Oxidation with Unknown Electronic Structure: Metal-Free Generation and EPR Study of Imide-N-oxyl Radicals. AB - Nitroxyl radicals are widely used in chemistry, materials sciences, and biology. Imide-N-oxyl radicals are subclass of unique nitroxyl radicals that proved to be useful catalysts and mediators of selective oxidation and CH-functionalization. An efficient metal-free method was developed for the generation of imide-N-oxyl radicals from N-hydroxyimides at room temperature by the reaction with (diacetoxyiodo)benzene. The method allows for the production of high concentrations of free radicals and provides high resolution of their EPR spectra exhibiting the superhyperfine structure from benzene ring protons distant from the radical center. An analysis of the spectra shows that, regardless of the electronic effects of the substituents in the benzene ring, the superhyperfine coupling constant of an unpaired electron with the distant protons at positions 4 and 5 of the aromatic system is substantially greater than that with the protons at positions 3 and 6 that are closer to the N-oxyl radical center. This is indicative of an unusual character of the spin density distribution of the unpaired electron in substituted phthalimide-N-oxyl radicals. Understanding of the nature of the electron density distribution in imide-N-oxyl radicals may be useful for the development of commercial mediators of oxidation based on N hydroxyimides. PMID- 26674212 TI - A Successful Endovascular Treatment of an Ischemic Stroke following Cardiac Surgery. AB - Ischemic stroke following cardiac surgery is one of the devastating complications that surgeons may encounter, and may lead to serious disabilities for the patient. The clinical course of such a complication may be prolonged if it is not treated properly. Making a quick decision when choosing a revascularization method is very helpful in this matter. Effective treatment options are usually limited. Neurointerventional maneuvers have recently emerged as a possible therapeutic modality in this field. We present the case of a 52-year-old woman who had open heart surgery in Queen Alia Heart Institute, Jordan, to replace a severely stenotic rheumatic mitral valve and repair a leaking tricuspid valve. Her surgery went smoothly with no major event. However, she developed a massive ischemic stroke during her recovery period despite being on adequate anticoagulation therapy. Urgent radiological work-up confirmed the diagnosis of ischemic stroke in the territory of the right middle cerebral artery. We chose a neuro-interventional method for her treatment, and mechanical thrombectomy was performed with a successful outcome and no apparent complications. PMID- 26674211 TI - Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis. AB - BACKGROUND: The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE: To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS: We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS: ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE: I. PMID- 26674213 TI - A meta-analysis of efficacy and safety of aripiprazole in adult and pediatric bipolar disorder in randomized controlled trials and observational studies. AB - BACKGROUND: Aripiprazole (ARP) has been shown to be effective in the treatment of bipolar disorder (BD). However, no prior investigation considered both randomized clinical trials (RCTs) and non-RCTs. We here evaluated the efficacy and safety of ARP compared with placebo (PCB) and other drugs at 3- and 12-weeks in adult and pediatric population including, for the first time, both observational and controlled studies. METHODS: All studies were systematically located by searching electronic sources (EMBASE, MEDLINE, CINHAIL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and ClinicalTrials.gov) till June 30th, 2015. The primary outcome was ARP efficacy (mean change from baseline in Young Mania Rating Scale); secondary outcomes regarded acceptability and safety. Results Sixteen RCTs and 6 non-RCTs met our inclusion criteria; 2505 and 2932 patients were included in the analyses of acute and stabilization phase, respectively. In both the acute and stabilization phases ARP efficacy was superior to PCB and comparable to other drugs. The safety profile was similar to other drugs considering in particular sedation, akathisia, weight gain, extrapyramidal and gastroenteric symptoms, with a significant lower risk of hyperprolactinemia particularly at 12-weeks. LIMITATIONS: Data on failed trials are generally limited. CONCLUSIONS: ARP resulted to be an effective treatment in children and adults with BD at 3- and 12-weeks both in a controlled experimental setting or in the real world clinical practice, being poorly associated with hyperprolactinemia. Larger studies are needed to confirm our results related to the maintenance phases and to the pediatric bipolar population. PMID- 26674216 TI - Polyaniline-Reduced Graphene Oxide Hybrid Nanosheets with Nearly Vertical Orientation Anchoring Palladium Nanoparticles for Highly Active and Stable Electrocatalysis. AB - We report a nearly vertical reduced graphene oxide (VrGO) nanosheet coupled with polyaniline (PANI) for supporting palladium (Pd) nanoparticles. The PANI-coupled VrGO (PANI@VrGO) nanosheet is prepared by a simple one-step electrodeposition technique ,and Pd nanoparticles are anchored on the support of PANI@VrGO through the spontaneous redox reaction of PANI with a palladium salt. The designed PANI@VrGO nanosheet efficiently exposes the surface of rGO sheets and stabilizes metal nanoparticles. Consequently, the Pd/PANI@VrGO electrocatalyst exhibits high catalytic activity and excellent durability for alcohol oxidation reaction. The proposed nanoarchitecture offers a new pathway to greatly promote the performances of rGO in various applications; moreover, this work provides a powerful and universal synthetic strategy for such an architecture. PMID- 26674214 TI - Peripheral sub-inflammation is associated with antidepressant consumption in schizophrenia. Results from the multi-center FACE-SZ data set. AB - OBJECTIVES: The relation between C-Reactive Protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a high rate of depression comorbidity. The objectives of this study were: (i) to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multicenter community dwelling sample of subjects with schizophrenia (ii) to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia. METHOD: 219 stable patients with schizophrenia (mean age=31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Axis I Disorders and Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels >3mg/L. Current medication was recorded. RESULTS: Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with body mass index (BMI) (p<0.0001), hypertriglyceridemia (p=0.0015), high waist circumference (p<0.0001), metabolic syndrome (p=0.0011), abdominal obesity (p<0.0001) and with antidepressant consumption (p=0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status, hypertension or high fasting glucose were not (all p>0.05). In a multivariate model, abnormal CRP was associated with antidepressant consumption independently of other confounding variables (adjusted Odds Ratio=2.8, 95% confidence interval 1.22-6.62). Metabolic syndrome was also independently associated with abnormal CRP (adjusted Odds Ratio=2.6, 95% confidence interval 1.01-6.71). CONCLUSION: Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression. The potential mechanisms were discussed. Antidepressant consumption should be systematically recorded in future studies exploring inflammation in schizophrenia. Future clinical trials of interventions directed at lowering the level of CRP and other inflammatory markers are discussed. PMID- 26674217 TI - Perfluoroalkyl Cobalt(III) Fluoride and Bis(perfluoroalkyl) Complexes: Catalytic Fluorination and Selective Difluorocarbene Formation. AB - Four perfluoroalkyl cobalt(III) fluoride complexes have been synthesized and characterized by elemental analysis, multinuclear NMR spectroscopy, X-ray crystallography, and powder X-ray diffraction. The remarkable cobalt fluoride (19)F NMR chemical shifts (-716 to -759 ppm) were studied computationally, and the contributing paramagnetic and diamagnetic factors were extracted. Additionally, the complexes were shown to be active in the catalytic fluorination of p-toluoyl chloride. Furthermore, two examples of cobalt(III) bis(perfluoroalkyl)complexes were synthesized and their reactivity studied. Interestingly, abstraction of a fluoride ion from these complexes led to selective formation of cobalt difluorocarbene complexes derived from the trifluoromethyl ligand. These electrophilic difluorocarbenes were shown to undergo insertion into the remaining perfluoroalkyl fragment, demonstrating the elongation of a perfluoroalkyl chain arising from a difluorocarbene insertion on a cobalt metal center. The reactions of both the fluoride and bis(perfluoroalkyl) complexes provide insight into the potential catalytic applications of these model systems to form small fluorinated molecules as well as fluoropolymers. PMID- 26674215 TI - The transcriptional coregulator PGC-1beta controls mitochondrial function and anti-oxidant defence in skeletal muscles. AB - The transcriptional coregulators PGC-1alpha and PGC-1beta modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1beta is poorly understood in skeletal muscle, a tissue of high mitochondrial content to produce ATP levels required for sustained contractions. Here we determine the physiological role of PGC-1beta in skeletal muscle using mice, in which PGC-1beta is selectively ablated in skeletal myofibres at adulthood (PGC-1beta((i)skm-/-) mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1beta((i)skm-/-) mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1beta((i)skm-/-) muscles leads to mitochondrial structural and functional abnormalities, impaired muscle oxidative capacity and reduced exercise performance. Moreover, enhanced free radical leak and reduced expression of the mitochondrial anti-oxidant enzyme Sod2 increase muscle oxidative stress. PGC-1beta is therefore instrumental for skeletal muscles to cope with high energetic demands. PMID- 26674218 TI - Medical Students' Perception about the Educational Environment in Western Maharashtra in Medical College using DREEM Scale. AB - INTRODUCTION: Educational Environment (EE) has significant impact on teaching learning, satisfaction, performance and academic progress of students. Feedback obtained through structured questionnaire designed for them can serve as tool for identifying and solving these EE related problems. OBJECTIVE: To assess the perceptions of medical students concerning their educational environment (EE) using Dundee Ready Education Environment Measure (DREEM) scale. MATERIALS AND METHODS: Study involved all three years medical students; surveyed with DREEM questionnaire consisted of 50 items based on the Likert 's scale (scores from 0 to 200); and 5 domains namely students' perceptions of learning (SPL), perceptions of teachers (SPT), academic self-perceptions (SAP), perceptions of atmosphere (SPA) and social self-perceptions (SSP). RESULTS: The overall total score on Likert's scale was 136 (interpretation: predominantly positive). The scores obtained in the different domains were 35.5 in SPL (interpretation: a more positive perception); 30.9 in SPT (interpretation: moving in the right direction); 21 in SAP (interpretation: feeling more in the positive side); 29.8 in SPA (interpretation: a more positive atmosphere); and 16.1 in SSP (interpretation: satisfactory. The DREEM score assigned by female students was significantly greater (p<0.05) than male students. The second-year students were more positive in their perception of EE (p<0.05). CONCLUSION: Overall, student's perception about EE was satisfactory. However, the item with score <2 points i.e. authoritarian/strict teachers, factual, teacher-centred learning, inability to memorize all, poor support system for bored, tired or stressed students during their academic life were the problem areas identified need to be revisited and improvised to further improve learning experience. PMID- 26674219 TI - Ultrasound-diagnosed bone and joint destruction as a typical image in advanced Charcots arthropathy - case report. AB - The paper presents a case of Charcot foot in a patient with long standing type 2 diabetes and complicated by peripheral neuropathy. It was initially diagnosed by an ultrasound examination and subsequently confirmed by an X-ray and an magnetic resonance imaging. Diabetic neuropathy is nowadays the most frequent cause of Charcot arthropathy, although it can be also a result of other diseases of the nervous system. In the acute phase the patient usually presents with edema, redness and increased temperature of the foot, which can suggest many other diagnoses including bacterial infection, gout, venous thrombosis or trauma. Because of its non specific clinical presentation and unsufficient awareness of the specificity of the diabetic foot syndrome among health professionals and the patients the diagnosis of this process is in many cases delayed. In the acute phase appropriate treatment needs to be initiated (mainly off loading and immobilization of the foot in a total contact cast), otherwise a rapidly progressing destruction of the bones and joints will usually begin, leading to fractures, dislocations and a severe foot deformity. Increased awareness among doctors taking care of the diabetic patients and appropriate use of the imaging methods can definitely improve efficacy of the diagnostic process and help to optimize the treatment of Charcot arthropathy. The standard approach usually includes use of radiography, magnetic resonance imaging and scintigraphy. In some cases a sonographer may be the first one to notice typical signs of bony destruction in a patient with Charcot arthropathy and suggest immediate further imaging in order to confirm the diagnosis and to minimize the risk of mutilating complications. PMID- 26674220 TI - Hypermetabolism: should cancer types, pathological stages and races be considered in assessing metabolism and could elevated resting energy expenditure be the therapeutic target in patients with advanced cancer? PMID- 26674222 TI - Antifungal Activities of Crude Extractum from Camellia semiserrata Chi (Nanshancha) Seed Cake Against Colletotrichum musae, Colletotrichum gloeosporioides and Penicillium italicum in vitro and in vivo Fruit Test. AB - Antifungal activities of crude extractum of Nanshancha Seed Cake (NSC), to inactivate postharvest pathogens were investigated. Highest inhibitory rate was found against C. musae, C. gloeosporioides and C. papaya P.Henn, which was much stronger than that by tea saponin. Compared to tea saponin, effects of NSC extractum was relatively weak and similar on C. gloeosporioides Penzig and P. italicum. In an in vivo study, best controlling effects by NSC extractum was found with banana anthracnose disease development, which showed no inhibitory effects by tea saponin. NSC extractum controlled in vitro C. musae growth through directly inhibiting germination rate and germ tube elongation, and causing distortation, rupture and indentation of C. musae mycelium. In banana fruit subject to C. musae inoculation, higher PAL, POD, GLU and CHT activity was observed in banana fruit treated with crude NSC extractum than that of water control fruits. Current study proved the best controlling effects of crude NSC extractum in C. musae in vitro and in vivo development, which through direct inhibition of C. musae growth and increasing defense system of the banana fruit. PMID- 26674221 TI - L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats. AB - This study assessed the effects of thyroid hormones on the enzymes involved in l arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. PMID- 26674223 TI - GC-elements controlling HRAS transcription form i-motif structures unfolded by heterogeneous ribonucleoprotein particle A1. AB - HRAS is regulated by two neighbouring quadruplex-forming GC-elements (hras-1 and hras-2), located upstream of the major transcription start sites (doi: 10.1093/nar/gku 5784). In this study we demonstrate that the C-rich strands of hras-1 and hras-2 fold into i-motif conformations (iMs) characterized under crowding conditions (PEG-300, 40% w/v) by semi-transitions at pH 6.3 and 6.7, respectively. Nondenaturing PAGE shows that the HRAS C-rich sequences migrate at both pH 5 and 7 as folded intramolecular structures. Chromatin immunoprecipitation shows that hnRNP A1 is associated under in vivo conditions to the GC-elements, while EMSA proves that hnRNP A1 binds tightly to the iMs. FRET and CD show that hnRNP A1 unfolds the iM structures upon binding. Furthermore, when hnRNP A1 is knocked out in T24 bladder cancer cells by a specific shRNA, the HRAS transcript level drops to 44 +/- 5% of the control, suggesting that hnRNP A1 is necessary for gene activation. The sequestration by decoy oligonucleotides of the proteins (hnRNP A1 and others) binding to the HRAS iMs causes a significant inhibition of HRAS transcription. All these outcomes suggest that HRAS is regulated by a G-quadruplex/i-motif switch interacting with proteins that recognize non B-DNA conformations. PMID- 26674224 TI - CDH1/E-cadherin and solid tumors. An updated gene-disease association analysis using bioinformatics tools. AB - Cancer is a group of diseases that causes millions of deaths worldwide. Among cancers, Solid Tumors (ST) stand-out due to their high incidence and mortality rates. Disruption of cell-cell adhesion is highly relevant during tumor progression. Epithelial-cadherin (protein: E-cadherin, gene: CDH1) is a key molecule in cell-cell adhesion and an abnormal expression or/and function(s) contributes to tumor progression and is altered in ST. A systematic study was carried out to gather and summarize current knowledge on CDH1/E-cadherin and ST using bioinformatics resources. The DisGeNET database was exploited to survey CDH1-associated diseases. Reported mutations in specific ST were obtained by interrogating COSMIC and IntOGen tools. CDH1 Single Nucleotide Polymorphisms (SNP) were retrieved from the dbSNP database. DisGeNET analysis identified 609 genes annotated to ST, among which CDH1 was listed. Using CDH1 as query term, 26 disease concepts were found, 21 of which were neoplasms-related terms. Using DisGeNET ALL Databases, 172 disease concepts were identified. Of those, 80 ST disease-related terms were subjected to manual curation and 75/80 (93.75%) associations were validated. On selected ST, 489 CDH1 somatic mutations were listed in COSMIC and IntOGen databases. Breast neoplasms had the highest CDH1 mutation rate. CDH1 was positioned among the 20 genes with highest mutation frequency and was confirmed as driver gene in breast cancer. Over 14,000 SNP for CDH1 were found in the dbSNP database. This report used DisGeNET to gather/compile current knowledge on gene-disease association for CDH1/E-cadherin and ST; data curation expanded the number of terms that relate them. An updated list of CDH1 somatic mutations was obtained with COSMIC and IntOGen databases and of SNP from dbSNP. This information can be used to further understand the role of CDH1/E-cadherin in health and disease. PMID- 26674225 TI - GPCR-drug interactions prediction using random forest with drug-association matrix-based post-processing procedure. AB - G-protein-coupled receptors (GPCRs) are important targets of modern medicinal drugs. The accurate identification of interactions between GPCRs and drugs is of significant importance for both protein function annotations and drug discovery. In this paper, a new sequence-based predictor called TargetGDrug is designed and implemented for predicting GPCR-drug interactions. In TargetGDrug, the evolutionary feature of GPCR sequence and the wavelet-based molecular fingerprint feature of drug are integrated to form the combined feature of a GPCR-drug pair; then, the combined feature is fed to a trained random forest (RF) classifier to perform initial prediction; finally, a novel drug-association-matrix-based post processing procedure is applied to reduce potential false positive or false negative of the initial prediction. Experimental results on benchmark datasets demonstrate the efficacy of the proposed method, and an improvement of 15% in the Matthews correlation coefficient (MCC) was observed over independent validation tests when compared with the most recently released sequence-based GPCR-drug interactions predictor. The implemented webserver, together with the datasets used in this study, is freely available for academic use at http://csbio.njust.edu.cn/bioinf/TargetGDrug. PMID- 26674226 TI - Preface. PMID- 26674227 TI - Green synthesis, characterization and catalytic activity of the Pd/TiO2 nanoparticles for the ligand-free Suzuki-Miyaura coupling reaction. AB - A green synthesis process was developed for production of the Pd/TiO2 nanoparticles (NPs) without using toxic, hazardous and dangerous materials. Myrtus communis L. leaf extract serves as a mild, renewable and non-toxic reducing agent. The advantages of this biosynthesis method include use of cheap, clean, nontoxic and environmentally benign precursors and simple procedures without time-consuming polymerization and problems with treatment of a highly viscous polymeric resin. More importantly, the synthesized Pd/TiO2 NPs presented excellent catalytic activity for ligand-free Suzuki-Miyaura coupling which could be easily separated from the reaction mixture and reused many times with no loss of activity. Therefore, these properties indicate demonstrative benefits of the catalyst. The Pd/TiO2 NPs was characterized by FESEM, TEM, FT-IR, UV-vis spectroscopy and EDS. PMID- 26674228 TI - Pathways from disordered to ordered nanostructures from defect guided dewetting of ultrathin bilayers. AB - Transitions from spinodal to pattern-guided dewetting of a bilayer of ultrathin films (<10nm) confined between a pair of patterned surfaces have been explored employing molecular dynamic (MD) simulations. The physical or chemical defects of different sizes and shapes are decorated on the confining substrates by either removal or addition of multiple layers of similar or dissimilar atoms. The simulations are performed to identify the transition from spinodal pathway to the heterogeneous nucleation route, with the variation in the size of the substrate patterns. The MD simulations reveal the limits beyond which the defects can guide the dewetting to generate ordered patterns of nanoscopic size and periodicity. Comparing the results obtained from the MD simulations with the more widely employed continuum dynamics approach highlights the importance of the MD approach in quantitatively analyzing the dynamics of the dewetting of ultrathin films. The study demonstrates that the pattern-guided dewetting of confined bilayers can lead to ordered holes, droplets, and stripes with size and periodicity less than 10nm, which are yet to be realized experimentally and can be of significance for a number of future applications. PMID- 26674229 TI - Antimicrobial and cell viability measurement of bovine serum albumin capped silver nanoparticles (Ag/BSA) loaded collagen immobilized poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV) film. AB - Bacterial infection of orthopedic devices has been a major concern in joint replacement procedures. Therefore, this study is aimed at formulating collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film loaded with bovine serum albumin capped silver nanoparticles (Ag/BSA NPs) to inhibit bacterial growth while retaining/promoting osteoblast cells viability. The nanoparticles loaded collagen immobilized PHBV film was characterized for its composition by X-ray Photoelectron Spectroscopy and Anodic Stripping Voltammetry. The extent of loading of Ag/BSA NPs on collagen immobilized PHBV film was found to depend on the chemistry of the functionalized PHBV film and the concentration of Ag/BSA NPs solution used for loading nanoparticles. Our results showed that more Ag/BSA NPs were loaded on higher molecular weight collagen immobilized PHEMA g-PHBV film. Maximum loading of Ag/BSA NPs on collagen immobilized PHBV film was observed when 16ppm solution was used for adsorption studies. Colony forming unit and optical density measurements showed broad antimicrobial activity towards Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa at significantly lower concentration i.e., 0.19 and 0.31MUg/disc, compared to gentamicin and sulfamethoxazole trimethoprim while MTT assay showed that released nanoparticles from Ag/BSA NPs loaded collagen immobilized PHBV film has no impact on MCTC3-E1 cells viability. PMID- 26674231 TI - Destabilising Pickering emulsions by drop flocculation and adhesion. AB - We have investigated how emulsions of water drops coated by organoclay particles destabilise in organic solvents. The drops destabilise and the emulsions undergo a fluid-solid transition if the particles are poorly wetted by the solvent. We show that the drops adhere together and form three-dimensional networks as the fraction of the poor-quality solvent in the mixture increases. Microscopic observations revealed that the drops coalesce into buckled, non-spherical shapes in mixtures rich in poor-quality solvent. A key finding is that destabilisation is favoured under conditions where the energy of adhesion between the particle layers coating drops is comparable to the energy required to detach the particles from the drops. Rupture of the interfacial layer produces particle flocs and uncoated, unstable water drops that settle out of the emulsion. PMID- 26674230 TI - Cellular uptake of poly(allylamine hydrochloride) microcapsules with different deformability and its influence on cell functions. AB - It is important to understand the safety issue and cell interaction pattern of polyelectrolyte microcapsules with different deformability before their use in biomedical applications. In this study, SiO2, poly(sodium-p-styrenesulfonate) (PSS) doped CaCO3 and porous CaCO3 spheres, all about 4MUm in diameter, were used as templates to prepare microcapsules with different inner structure and subsequent deformability. As a result, three kinds of covalently assembled poly(allylaminehydrochloride)/glutaraldehyde (PAH/GA) microcapsules with similar size but different deformability under external osmotic pressure were prepared. The impact of different microcapsules on cell viability and functions are studied using smooth muscle cells (SMCs), endothelial cells (ECs) and HepG2 cells. The results demonstrated that viabilities of SMCs, ECs and HepG2 cells were not significantly influenced by either of the three kinds of microcapsules. However, the adhesion ability of SMCs and ECs as well as the mobility of SMCs, ECs and HepG2 cells were significantly impaired after treatment with microcapsules in a deformability dependent manner, especially the microcapsules with lower deformability caused higher impairment on cell functions. The cellular uptake kinetics, uptake pathways, intracellular distribution of microcapsules are further investigated in SMCs to reveal the potential mechanism. The SMCs showed faster uptake rate and exocytosis rate of microcapsules with lower deformability (Cap@CaCO3/PSS and Cap@CaCO3), leading to higher intracellular accumulation of microcapsules with lower deformability and possibly larger retardation of cell functions. The results pointed out that the deformability of microcapsules is an important factor governing the biological performance of microcapsules, which requires careful adjustment for further biomedical applications. PMID- 26674232 TI - Carbon dots on based folic acid coated with PAMAM dendrimer as platform for Pt(IV) detection. AB - Carbon quantum dots (CQDs) coated with poly(amidoamine) (PAMAM-NH2) dendrimer are prepared from folic acid and phosphoric acid under a hydrothermal procedure. The obtained nanoparticles are successfully used as fluorescent sensor for Pt(IV) (in the form of chloroplatinate ion). CQDs possess many attractive features including uniform dispersion with average size about 13nm for unmodified particles and, ~30nm when they are coated with PAMAM-NH2 dendrimer. The synthesized nanoparticles have been characterized by elemental analysis, attenuated total reflectance (ATR), X-ray photoelectron (XPS) and Raman spectroscopies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and steady-state and life-time fluorescence. CQDs are used as fluorescent sensor of Pt(IV) ion in aqueous media showing linear quenching effect of their fluorescence. The results obtained demonstrated a limit of detection of 657nM with an accuracy of the method of 0.13% (as RSD, n=10) and sensitivity of 78nM. Moreover, with the presence of other interference species, good results are obtained when applied in real samples from platinum nanoparticles synthesis. The dissolved platinum ions can be quantified in the range 6-96MUM with an accuracy of 2.5%. PMID- 26674233 TI - Hydrolysis driven surface activity of esterquat surfactants. AB - HYPOTHESIS: Surface activity of selected cleavable esterquat cationic surfactants is determined by the synergistic effect of surface active products of their hydrolysis. EXPERIMENTS: Interfacial behavior of two classes of esterquat surfactants, quaternary alkylammmoniumesters and amino acid betaine (trimethylglycine) esters of fatty acids were examined both experimentally and theoretically. The surface tension measurements at air/water interface were performed by the pendant drop shape analysis method, then the obtained isotherms were theoretically described by the model of adsorption of ionic/non-ionic surfactants mixtures taking into account the presence of surface active products of surfactant hydrolysis. FINDINGS: We found that surface activity of the mixture of surface active compounds resulting from the esterquat basic hydrolysis increases with time and it is higher when the ester carbonyl group is connected with the quaternary amine by bridging oxygen than in the inverted (betaine ester type) arrangement. That is, in the first case, the consequence of strong synergistic effect between the cationic esterquat surfactant and the anionic product of its hydrolysis - dodecanoate ion, while in the second case, the non ionic hydrolysis product - dodecanol exhibits much weaker synergy. The addition of side CH3 group into the esterquat head-group slows down the hydrolysis that leads to the lower surface activity of the resulting mixture. PMID- 26674234 TI - Adsorption of carbendazim pesticide on plasmonic nanoparticles studied by surface enhanced Raman scattering. AB - Surface-Enhanced Raman Spectra (SERS) of methyl N-(1H-benzimidazol-2-yl)carbamate (MBC), usually named carbendazim, have been recorded on silver colloids at different pH values. In order to identify the neutral, protonated or deprotonated species of MBC that originate the SERS, the vibrational wavenumbers of these three isolated forms and linked to a silver atom have been predicted by carrying out DFT calculations. The results indicate that the active SERS species in the studied pH range correspond to the neutral MBC and its deprotonated ion in the amidate form. According to theoretical calculations, neutral MBC is linked to the metal through the imidazolic nitrogen atom, while the deprotonated MBC could be linked through the imidazolic nitrogen together with the amidic nitrogen atom or the carbonyl oxygen atom. Both adsorbed species, neutral and deprotonated, have the benzimidazolic ring orientated almost perpendicular to the silver surface and no molecular reorientation has been detected. pH of the bulk controls the relative abundance of the neutral MBC and its amidate anion which can be monitored through the intensities of the SERS bands recorded at about 1230 and 1270cm(-1). These two key bands correspond to the in-plane NH deformation of amidic and imidazolic groups, respectively. PMID- 26674235 TI - Kinetic studies of nucleation and growth of palladium nanoparticles. AB - In this paper, the kinetic studies of nucleation and growth processes of palladium nanoparticles formation are presented. As a palladium precursor the chloride complex of Pd(II) and as a reductant l-ascorbic acid, were used. Kinetic studies were conducted under different experimental conditions such as initial concentration of metal ions, ascorbic acid, chloride ions as well as at different temperature and ionic strength. Using Finke-Watzky model kinetic rate constants were established and discussed. The value of activation enthalpy and entropy have also been determined using Eyring-Polanyi equation. For all obtained colloids, plasmons and values of hydrodynamic radius were registered. PMID- 26674236 TI - Thermoreversible crystallization of charged colloids due to adsorption/desorption of ionic surfactants. AB - We report that charged colloids exhibit thermoreversible crystallization via the adsorption of ionic surfactants onto particle surfaces. Due to the temperature dependence of the adsorption quantity, the colloids crystallized upon cooling and melted upon heating. To clarify the influences of surfactant adsorption on the crystallization, polystyrene (PS) particles dispersed in ethylene glycol (EG)/water mixtures were employed, enabling continuous tuning of the adsorption quantity by changing the EG concentration. The thermoreversible crystallization/melting behavior was found to be mainly attributable to changes in the ionic strength of the medium resulting from variation in the concentration of the non-adsorbed ionic surfactant molecules with temperature. We expect that the present findings will be useful for fine control of colloidal crystallization and the further study of colloidal crystallization in low permittivity media. PMID- 26674237 TI - Inkjet printed highly porous TiO2 films for improved electrical properties of photoanode. AB - The aim of presented work is to show the improvements obtained in the properties of TiO2 films for dye sensitized solar cells fabricated by inkjet printing using an innovative methodology. We describe the development and properties of TiO2 based inks used in a lab-scale printer, testing various commercial TiO2 pastes. The porosity of the deposited inkjet printed TiO2 films is much higher than using the conventional "doctor blade" deposition technique, as the ink solvent evaporates during the droplet fly from the nozzle to the substrate due to its picoliter volume and the applied heating of a printing stage (70 degrees C). Thanks to higher surface area, the dye sensitized solar cells incorporating inkjet printed TiO2 film gave higher efficiencies (etamax~3.06%) than the more compact films obtained by the "doctor blade" method (etamax~2.56%). Furthermore, electrochemical analysis indicates that for whole tested thickness range, the inkjet printed layers have higher effective electron diffusion length indicating their better transport properties. PMID- 26674238 TI - An EDTA-beta-cyclodextrin material for the adsorption of rare earth elements and its application in preconcentration of rare earth elements in seawater. AB - The separation and recovery of Rare earth elements (REEs) from diluted aqueous streams has attracted great attention in recent years because of ever-increasing REEs demand. In this study, a green synthesized EDTA-cross-linked beta cyclodextrin (EDTA-beta-CD) biopolymer was prepared and employed in adsorption of aqueous REEs, such as La(III), Ce(III), and Eu(III). EDTA acts not only as cross linker but also as coordination site for binding of REEs. The adsorption properties for the adsorption of REEs by varying experimental conditions were carried out by batch tests. The kinetics results revealed that the surface chemical sorption and the external film diffusion were the rate-determining steps of the adsorption process. The obtained maximum adsorption capacities of EDTA beta-CD were 0.343, 0.353, and 0.365mmolg(-1) for La(III), Ce(III) and Eu(III), respectively. Importantly, the isotherms fitted better to Langmuir than Freundlich and Sips models, suggesting a homogenous adsorption surface for REEs on the adsorbent. Moreover, the multi-component adsorption, which was modeled by extended Sips isotherms, revealed adsorbent's selectivity to Eu(III). More significantly, the successful recoveries of the studied ions from tap water and seawater samples makes EDTA-beta-CD a promising sorbent for the preconcentration of REEs from diluted aqueous streams. PMID- 26674239 TI - Effective photocatalytic efficacy of hydrothermally synthesized silver phosphate decorated titanium dioxide nanocomposite fibers. AB - Hierarchical Ag3PO4/TiO2 nanocomposite fibers were prepared by combining electrospinning technique and hydro-thermal growth method. As-synthesized samples were characterized by using field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Photoluminescence (PL), and Fourier transform infra-red (FT-IR) spectroscopy. The FE-SEM image revealed a uniform decoration of Ag3PO4 nanoparticles without aggregation on primary TiO2 nanofibers. The photocatalytic and antibacterial studies were performed and results were shown that the Ag3PO4/TiO2 nanocomposite fibers show an enhanced photocatalytic and antibacterial activity toward the degradation of dye methylene blue and bacteria (Escherichia coli, Staphylococcus aureus) respectively. Our results can provide new insights of Ag3PO4/TiO2 nanocomposite fibers for the potential applications in antibacterial and waste water treatment. PMID- 26674240 TI - Molecular simulation of the effects of humidity and of interfacial Si- and B hydroxyls on the adhesion energy between glass plates. AB - Adhesion energies for sub-micron particles cannot be accurately calculated with macro-scale theories, in part because heterogeneities in surface morphology and chemistry play a significant role. Atomistic models have been used previously to quantify adhesion energies in wet environments for pure silica surfaces. To extend such modeling to more complex glass materials, we adopt a more comprehensive amorphous glass potential, and use a simplified approach to define the interaction between the hydroxylated surface and SPC/E water. We compute adhesion energies for pure SiO2, and 90mol% SiO2+10mol% B2O3, in dry and humid conditions. We find that the addition of B2O3 reduces adhesion, due to multiple effects which result in reduced hydrogen bonding. At high RH, the water between the plates forms a clear liquid bridge, whereas at the lowest RH, the water connects in chains of hydrogen bonded molecules that form and break during the adhesion process, so that capillary forces do not come into play. We also find that for under-hydroxylated pure SiO2 surfaces, a transitional state which may be found after heating or during glass formation, adhesion energies are the highest. PMID- 26674241 TI - Direct surface modification of ligand-free silicon quantum dots prepared by femtosecond laser ablation in deionized water. AB - Amine-terminated, ultra-small silicon nanoparticles (Si-NPs) were prepared in one step avoiding the conventional chemical or thermal treatment of Si surface, by introducing organosilane in Si-NPs colloidal solution freshly prepared by ultra fast laser ablation of silicon target in deionized water. Surface chemistry studies of Si-NPs conducted by Raman and Fourier infrared spectroscopy demonstrated the hydroxyl-terminated surface of Si-NPs. The reactivity of hydroxyl-terminated surface with aminopropyltriethoxysilane in aqueous solution was investigated. Electron microscopy, dynamic light scattering, infrared spectroscopy and stability studies confirmed the successful functionalization of Si-NPs leading to 5nm Si dots covered by aminopropyltriethoxysilane thick layer. Detailed infrared spectroscopy analysis of the Si-O-Si region as a function of immersion time revealed the formation of interfacial Si-O bonds between the organosilane and hydroxyl groups of the nanoparticles. The biocompatible Si nanostructure containing amine functional group prepared using a one-step green protocol opens the route for biomedical applications and successful translation into clinical setting, as bio-labels, contrast agents and vector delivery. PMID- 26674242 TI - Green synthesis of Pd/RGO/Fe3O4 nanocomposite using Withania coagulans leaf extract and its application as magnetically separable and reusable catalyst for the reduction of 4-nitrophenol. AB - A reduced graphene oxide (RGO)/Fe3O4 based nanocomposite with palladium nanoparticles (Pd NPs) has been synthesized via a green route by Withania coagulans leaf extract as a reducing and stabilizing agent and its catalytic activity has been tested for the reduction of 4-nitrophenol (4-NP) in water at room temperature. The hydroxyl groups of phenolics in W. coagulans leaf extract is directly responsible for the reduction of Pd(2+), Fe(3+) ions and GO. The nanocomposite was characterized by X-ray diffraction (XRD), fourier transformed infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FE SEM), energy dispersive X-ray spectroscopy (EDS), Vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM). Furthermore, due to the magnetic separability and high stability of the composite the catalyst can be recovered and recycled several times without marked loss of activity. PMID- 26674243 TI - Protein-based emulsion electrosprayed micro- and submicroparticles for the encapsulation and stabilization of thermosensitive hydrophobic bioactives. AB - This work shows the potential of emulsion electrospraying of proteins using food grade emulsions for the microencapsulation and enhanced protection of a model thermosensitive hydrophobic bioactive. Specifically, gelatin, a whey protein concentrate (WPC) and a soy protein isolate (SPI) were compared as emulsion stabilizers and wall matrices for encapsulation of alpha-linolenic acid. In a preliminary stage, soy bean oil was used as the hydrophobic component for the implementation of the emulsion electrospraying process, investigating the effect of protein type and emulsion protocol used (i.e. with or without ultrasound treatment) on colloidal stability. This oil was then substituted by the omega-3 fatty acid and the emulsions were processed by electrospraying and spray-drying, comparing both techniques. While the latter resulted in massive bioactive degradation, electrospraying proved to be a suitable alternative, achieving microencapsulation efficiencies (MEE) of up to ~70%. Although gelatin yielded low MEEs due to the need of employing acetic acid for its processing by electrospraying, SPI and WPC achieved MEEs over 60% for the non-sonicated emulsions. Moreover, the degradation of alpha-linolenic acid at 80 degrees C was significantly delayed when encapsulated within both matrices. Whilst less than an 8% of its alkene groups were detected after 27h of thermal treatment for free alpha-linolenic acid, up to 43% and 67% still remained intact within the electrosprayed SPI and WPC capsules, respectively. PMID- 26674244 TI - Preparation, characterization and catalytic activity of CoFe2O4 nanoparticles as a magnetically recoverable catalyst for selective oxidation of benzyl alcohol to benzaldehyde and reduction of organic dyes. AB - The CoFe2O4 nanoparticles (NPs) performance was studied in the oxidation of benzyl alcohol (BzOH) to benzaldehyde (BzH) with hydrogen peroxide as an oxidant under solvent-free conditions. The influences of reaction conditions like the amount of catalyst, the molar ratio of H2O2:BzOH, reaction temperature and times on the oxidation of BzOH by using CoFe2O4 NPs were investigated in details. Under optimum conditions, excellent result, >99% conversation of BzOH to BzH as the only product, was obtained. The nanocatalyst was also used for the reduction of 4 nitrophenol (4-NP), Congo red (CR), Methylene blue (MB) in water at room temperature. The magnetic properties of the catalyst provided a convenient and easy route for the separation of the catalyst from the reaction mixture by an external bar magnet. No obvious loss of activity was observed when the spent catalyst reused in three consecutive runs. PMID- 26674245 TI - Green chemistry approach for the synthesis of ZnO-carbon dots nanocomposites with good photocatalytic properties under visible light. AB - We report on a simple and one-pot synthetic method to produce ZnO/carbon quantum dots (ZnO/CQDs) nanocomposites. The morphological features and chemical composition of the nanocomposites were characterized using X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analyses (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The optical properties of the nanocomposites were examined using UV-visible (UV-vis) spectrophotometry. The photocatalytic activity of the ZnO/CQDs was evaluated for the degradation of a model organic pollutant, rhodamine B, under visible light irradiation at room temperature. The highly efficient photodegradation capability of the nanocomposite was demonstrated by comparison with ZnO particles, prepared using identical experimental conditions. Overall, the present approach adheres to green chemistry principles and the nanocomposite holds promise for the development of remarkably efficient catalytic systems. PMID- 26674246 TI - Impact of self esteem on risky sexual behaviors among Nigerian adolescents. AB - Although improved knowledge is often the first approach in HIV prevention for adolescents, studies have shown that despite being well informed, adolescents still engage in risky sexual behavior (RSB). Low self-esteem has been considered to be a psychological explanation for behavioral problems, but little is known about the impact of self-esteem on RSB among adolescents in Nigeria. The purpose of this study was to determine whether adolescents with high self-esteem demonstrate lower RSB compared to those with low self-esteem. We conducted a cross-sectional survey of 361 adolescents in 9 secondary schools in Jos Plateau, Nigeria. The Rosenberg Self Esteem Scale was used to measure self-esteem and the Brief HIV Screener (BHS) was used to measure RSB. All data were analyzed using SPSS 21. Chi square and odds ratios were calculated to determine differences in BHS questions based on predetermined low or high self-esteem categories. Independent t-test were utilized to determine difference in mean BHS scores based on self-esteem categories. Participants were 169 male (46.8%) and 192 female (53.2%) with a mean age of 16.9. Mean self-esteem score was 27.6 with no significant difference in self-esteem scores by gender. Adolescents with low self esteem were 1.7 times more likely to be sexually active and had a higher mean BHS scores compared to adolescents with high self-esteem. Programs aimed at reducing RSB and in-turn HIV/AIDS should consider interventions to raise adolescents' self esteem. PMID- 26674247 TI - Role of sonography in assessing complications after laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy, which was introduced to the arsenal of surgical procedures in the middle of the 1980s, is a common alternative for conventional cholecystectomy. Its primary advantage is less invasive character which entails shorter hospitalization and faster recovery. Nevertheless, the complications of both procedures are comparable and encompass multiple organs and tissues. The paper presents ultrasound presentation of the surgical bed after laparoscopic cholecystectomy and of complications associated with this procedure. In the first week following the surgery, the presence of up to 60 ml of fluid in the removed gallbladder bed should be considered normal in certain patients. The fluid will gradually absorb. In single cases, slight amounts of fluid are detected in the peritoneal cavity, which also should not be alarming. Carbon dioxide absorbs from the peritoneal cavity within two days. Ultrasound assessment of the surgical bed after cholecystectomy is inhibited by hemostatic material left during the surgery. Its presentation may mimic an abscess. In such cases, the decisive examination is magnetic resonance imaging but not computed tomography. On the other hand, rapidly accumulating fluid around the liver is an alarming symptom, particularly when there is inadequate blood supply or when peritoneum irritation symptoms develop. Depending on the suspected cause of the patient's deteriorating condition, it is essential to perform urgent computed tomography angiography, celiac angiography or endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. The character of the fluid collection may be determined by its ultrasound-guided puncture. This procedure allows for aspiration of fluid and placement of a drain. Moreover, transabdominal ultrasound examination after laparoscopic cholecystectomy may contribute to the identification of: dropped stones in the right hypochondriac region, residual fragment of the gallbladder with possible concretions, undiagnosed choledocholithiasis, existing cholestasis, pseudoaneurysm of the hepatic artery, portal vein thrombosis and hematoma as well as hernias of the abdominal walls. Moreover, ultrasound examination helps to identify optimal sites in the abdominal integuments, which enables collision-free access to the peritoneal cavity. PMID- 26674248 TI - Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy. AB - BACKGROUND AND AIM: It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD. METHODS: The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients. RESULTS: The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase alpha, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) gamma compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. CONCLUSIONS: Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARgamma, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD. GENERAL SIGNIFICANCE: These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD. PMID- 26674249 TI - Detection and Quantification of Free Radicals in Peroxisomal Disorders: A Comparative Study with Oxidative Stress Parameters. AB - INTRODUCTION: Free radicals have been thought to participate in pathogenesis of peroxisomal disorders. OBJECTIVE: The aim of the work is to detect free oxide radicals in blood of patients with peroxisomal disorders and to study their relation with various oxidative stress parameters. MATERIALS AND METHODS: Twenty patients with peroxisomal disorders and 14 age and sex matched healthy subjects were included in the study. Patients with peroxisomal disorders were subdivided according to diagnosis into peroxisomal biogenesis disorders and single enzyme deficiency. Oxidative stress was evaluated in both patients and control subjects by assessment of free radicals, malondialdehyde, nitric oxide metabolites and superoxide dismutase. RESULTS: There was increase in free radicals, malondialdehyde, nitric oxide metabolites in patients compared with control subjects. However, there was decrease in superoxide dismutase levels in patients compared with control subjects. CONCLUSION: We concluded that there is excess free radicals production accompanied with decrease in antioxidant defenses in patients with peroxisomal disorders. These results strongly support a role of free radicals in the pathophysiology of peroxisomal disorders and strengthen the importance of oxidative stress phenomenon in peroxisomal disorders pathogenesis. PMID- 26674250 TI - DockTope: a Web-based tool for automated pMHC-I modelling. AB - The immune system is constantly challenged, being required to protect the organism against a wide variety of infectious pathogens and, at the same time, to avoid autoimmune disorders. One of the most important molecules involved in these events is the Major Histocompatibility Complex class I (MHC-I), responsible for binding and presenting small peptides from the intracellular environment to CD8(+) T cells. The study of peptide:MHC-I (pMHC-I) molecules at a structural level is crucial to understand the molecular mechanisms underlying immunologic responses. Unfortunately, there are few pMHC-I structures in the Protein Data Bank (PDB) (especially considering the total number of complexes that could be formed combining different peptides), and pMHC-I modelling tools are scarce. Here, we present DockTope, a free and reliable web-based tool for pMHC-I modelling, based on crystal structures from the PDB. DockTope is fully automated and allows any researcher to construct a pMHC-I complex in an efficient way. We have reproduced a dataset of 135 non-redundant pMHC-I structures from the PDB (Calpha RMSD below 1 A). Modelling of pMHC-I complexes is remarkably important, contributing to the knowledge of important events such as cross-reactivity, autoimmunity, cancer therapy, transplantation and rational vaccine design. PMID- 26674252 TI - Increased hypoxemia in patients with COPD and pulmonary hypertension undergoing bronchoscopy with biopsy. AB - BACKGROUND AND OBJECTIVE: Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB), but data concerning the degree of PH are often lacking. We investigated whether COPD patients with PH who undergo bronchoscopy are at greater risk for complications. METHODS: This prospective study included 207 consecutive COPD patients undergoing FB. All underwent an echo-Doppler to evaluate pulmonary artery pressure on the day of the bronchoscopy procedure. Pulmonologists were blinded to the echocardiogram results. RESULTS: A total of 167 patients (80.7%) had normal pulmonary pressure. The remaining 40 patients (19.3%) had PH: 27 (13.0%) mild, eight (3.9%) moderate, and five (2.4%) severe. Noninvasive hemodynamic parameters between groups before and after FB were similar. Two patients with normal pulmonary pressure developed supraventricular tachycardia. None developed hemodynamically significant dysrhythmia. Bleeding episodes between groups in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) did not differ. PH patients who underwent BAL and TBB had decreased O2 saturation during the procedure compared with the non-PH group (23.5% vs 6.9%, P=0.033). No deaths were attributable to FB. CONCLUSION: PH is common among COPD patients undergoing FB. PH patients undergoing BAL and TBB are at higher risk of decreased O2 saturation than those without PH. Further studies should assess the risk among COPD patients with moderate-to-severe PH. PMID- 26674251 TI - Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy. AB - Long-term survival and antitumor immunity of adoptively transferred CD8(+) T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (DeltaPsim). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low DeltaPsim-sorted CD8(+) T cells. Transfer of these low-DeltaPsim T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-DeltaPsim cells. Use of DeltaPsim-based sorting to enrich for cells with superior metabolic features was observed in CD8(+), CD4(+) T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer. PMID- 26674253 TI - Dark chocolate supplementation reduces the oxygen cost of moderate intensity cycling. AB - BACKGROUND: Dark chocolate (DC) is abundant in flavanols which have been reported to increase the bioavailability and bioactivity of nitric oxide (NO). Increasing NO bioavailability has often demonstrated reduced oxygen cost and performance enhancement during submaximal exercise. METHODS: Nine moderately-trained male participants volunteered to undertake baseline (BL) measurements that comprised a cycle VO(2max) test followed by cycling at 80% of their established gas exchange threshold (GET) for 20-min and then immediately followed by a two-minute time trial (TT). Using a randomised crossover design participants performed two further trials, two weeks apart, with either 40 g of DC or white chocolate (WC) being consumed daily. Oxygen consumption, RER, heart rate and blood lactate (BLa) were measured during each trial. RESULTS: DC consumption increased GET and TT performance compared to both BL and WC (P < 0.05). DC consumption increased VO(2max) by 6% compared to BL (P < 0.05), but did not reach statistical significance compared to WC. There were no differences in the moderate-intensity cycling for VO2, RER, BLa and heart rate between conditions, although, VO2 and RER exhibited consistently lower trends following DC consumption compared to BL and WC, these did not reach statistical significance. CONCLUSION: Chronic supplementation with DC resulted in a higher GET and enhanced TT performance. Consequently, ingestion of DC reduced the oxygen cost of moderate intensity exercise and may be an effective ergogenic aid for short-duration moderate intensity exercise. PMID- 26674254 TI - Curcumin loaded mesoporous silica: an effective drug delivery system for cancer treatment. AB - In the present study, we report the delivery of anti-cancer drug curcumin to cancer cells using mesoporous silica materials. A series of mesoporous silica material based drug delivery systems (S2, S4 and S6) were first designed and developed through the amine functionalization of KIT-6, MSU-2 and MCM-41 followed by the loading of curcumin. The curcumin loaded materials were characterized with several physico-chemical techniques and thoroughly screened on cancer cells to evaluate their in vitro drug delivery efficacy. All the curcumin loaded silica materials exhibited higher cellular uptake and inhibition of cancer cell viability compared to pristine curcumin. The effective internalization of curcumin in cancer cells through the mesoporous silica materials initiated the generation of intracellular reactive oxygen species and the down regulation of poly ADP ribose polymerase (PARP) enzyme levels compared to free curcumin leading to the activation of apoptosis. This study shows that the anti-cancer activity of curcumin can be potentiated by loading onto mesoporous silica materials. Therefore, we strongly believe that mesoporous silica based curcumin loaded drug delivery systems may have future potential applications for the treatment of cancers. PMID- 26674255 TI - Patient Perceptions of Patient-Centered Medical Home Characteristics and Satisfaction with Free Clinic Services. AB - The patient-centered medical home (PCMH) is a model of health care delivery designed to improve patient health outcomes by increasing the effectiveness of primary care. The effectiveness of PCMH on vulnerable populations is still largely unknown. The purpose of this study was to examine the relationship between patient perceptions of PCMH characteristics and patient satisfaction among Spanish-speaking and non-Spanish-speaking patients receiving health care at free clinics. A self-administered survey was used to collect data in 2 free clinics in the United States in 2013. Patients were primarily young and female; 44% were Spanish speaking. Patient perceptions of PCMH characteristics were assessed using multi-item Consumer Assessment of Healthcare Providers and Systems scales developed by the Agency for Healthcare Research and Quality. Patient satisfaction was assessed as satisfaction with care received at the clinic and willingness to recommend the provider. Multivariate logistic regression modeled the association between PCMH components and these 2 patient satisfaction measures. In adjusted analyses among Spanish speakers, satisfaction with clinic care was associated with staff helpfulness (OR = 6.03, 95% CI = 1.87-19.46) and no perceived discrimination (OR = 2.55, 95% CI = 1.22-5.33). For non-Spanish speakers, provider communication and politeness significantly increased odds of satisfaction with clinic services. Provider communication was strongly associated with patients' intention to recommend the provider to others for both Spanish speakers and non-Spanish speakers (OR = 4.83, 95% CI = 1.35-17.24; OR = 5.42, 95% CI = 1.54-19.09, respectively). Findings suggest that interpersonal characteristics of providers and clinic staff are critical to patient satisfaction among vulnerable populations served by free clinics. Future studies should examine PCMH components and clinical outcomes among this population. PMID- 26674256 TI - Characterisation of a chromosomally-encoded extended-spectrum beta-lactamase gene blaPER-3 in Aeromonas caviae of chicken origin. PMID- 26674257 TI - Effects of Market, E-Marketing, and Technology Orientations on Innovativeness and Performance in Turkish Health Organizations. AB - This article investigates the effects of strategic orientation on innovativeness and performance in health organizations in Turkey. We hypothesize that market, e marketing, and technology orientations positively affect innovativeness and performance. Market and technology orientations are found not have a significant effect on performance, but e-marketing orientation and innovativeness have a significant and positive effect. We also investigate indirect effects on innovativeness and performance. The analyses of direct and indirect effects are an important contribution to understanding relationships among research variables. PMID- 26674258 TI - Who Is the Biggest Loser? Fat News Coverage Is a Barrier to Healthy Lifestyle Promotion. AB - Through a textual and visual analysis of online news stories and public commentary about fat bodies, this article provides insights into the media's reporting on the "war on obesity." It identifies the stigmatizing role that the media plays. Specifically, the media draws on five key discourses in constructing fat bodies: pathologized, gazed upon, marginalized, controlled, and gendered. As news media coverage influences how society views health and policy issues, we argue that social marketers need to take an active role in changing the public's antifat attitudes through healthy lifestyle promotion tactics and strategies that reduce weight stigma. PMID- 26674260 TI - Muscles - histology, micro/macroanatomy and US anatomy, a brand new perspective. PMID- 26674259 TI - Why Does Exercise "Trigger" Adaptive Protective Responses in the Heart? AB - Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to "trigger" cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study. PMID- 26674261 TI - Current Perspective on the Pathogenesis of Small Intestinal Neuroendocrine Tumors: Progress in Biomarkers and Molecular Events. AB - BACKGROUND: Neuroendocrine tumors of the gastrointestinal tract differ in their histopathologic and clinical presentation. Small intestinal neuroendocrine tumors (SI-NETs), representing only a small portion within gastrointestinal malignancies, are often associated with a delayed diagnosis due to their non specific symptoms. The increased incidence of SI-NETs during the last decades demands earlier diagnosis and more effective treatment, which both rely on a better understanding on the underlying molecular mechanisms. SUMMARY: The purpose of this review is to discuss the biomolecular changes responsible for the pathogenesis of SI-NETs, and potential biomarkers in the diagnostic and prognostic evaluation. PMID- 26674262 TI - Phenytoin Induced Osteopathy -Too Common to be Neglected. AB - Anticonvulsants have the broad spectrum of side effects on the bone that are collectively known as osteopathy. Anticonvulsant induced osteopathy can have detrimental consequences. We present an unusual case that uniquely highlights both adverse effects of phenytoin on bone metabolism and side effects of its overtreatment. A 29-year-old lady came for evaluation of metabolic bone disease. Since last one year, she had severe bilateral hip pain resulting in restriction of movements. She was taking phenytoin 300 mg daily for last ten years for a seizure disorder. During evaluation at another center, she was diagnosed to have vitamin D deficiency, osteomalacia and secondary hyperparathyroidism. She received recombinant parathormone, high doses of vitamin D along with phenytoin. She presented at our centre with persistent pain and hypervitaminosis D. We stopped recombinant PTH, vitamin D and changed phenytoin to levetiracetam. Her condition improved over next six months with normalization of vitamin D. Thus, patients on phenytoin should be actively screened for side effects and the appropriate preventive and correctional measures should be undertaken. While managing these side effects overtreatment should be avoided. PMID- 26674263 TI - Was Hypervascular Hepatocellular Carcinoma Visible on Previous Gadoxetic Acid Enhanced Magnetic Resonance Images? AB - BACKGROUND: During the follow-up of patients with chronic liver disease, hypervascular hepatocellular carcinomas (HCCs) can develop either from pre existing high-risk nodules or by de novo hepatocarcinogenesis. The purpose of this study was to evaluate, by retrospective analysis, the detectability and signal intensity on previous hepatocyte-phase gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) of hypervascular HCC initially detected on current EOB-MRIs. METHODS: We examined 50 initially detected hypervascular HCCs that showed typical enhancement features on EOB-MRI in 39 patients whose previous EOB-MRI images obtained 6-19 months earlier were available. The detectability of each hypervascular HCC on the hepatocyte phase images of previous EOB-MRIs was assessed. The imaging features on hepatocyte-phase images of previous EOB-MRIs at the locations where hypervascular HCCs were found on the current EOB-MRI images were classified as detectable or undetectable. The signal intensities of detectable nodules (defined as group A) on hepatocyte-phase images of previous EOB-MRIs were classified as hypo-, iso-, or hyperintensity. Nodules undetectable on the hepatocyte-phase images of previous EOB-MRIs were assigned to group B. RESULTS: Twenty-two (22/50, 44%) hypervascular HCCs were detectable on the earlier hepatocyte phase images (group A). In contrast, 28 (28/50, 56%) hypervascular HCCs were not detectable on the hepatocyte phase of earlier EOB-MRI images (group B). CONCLUSION: When the previous EOB-MRI images were used as the reference, more than half (28/50, 56%) of hypervascular HCCs initially appearing on the current EOB-MRI images were found not to have developed from nodules detectable on the previous MRIs through the traditionally accepted process of multistep carcinogenesis. Instead, they seemed to have developed via an "imaging-occult" process of carcinogenesis in patients with chronic liver diseases. PMID- 26674265 TI - Dynamic left ventricular outflow tract obstruction: underestimated cause of hypotension and hemodynamic instability. AB - Left ventricular outflow tract obstruction, which is typically associated with hypertrophic cardiomyopathy, is the third most frequent cause of unexplained hypotension. This underestimated problem may temporarily accompany various diseases (it is found in even <1% of patients with no tangible cardiac disease) and clinical situations (hypovolemia, general anesthesia). It is currently assumed that left ventricular outflow tract obstruction is a dynamic phenomenon, the occurrence of which requires the coexistence of predisposing anatomic factors and a physiological condition that induces it. The diagnosis of left ventricular outflow tract obstruction should entail immediate implementation of the therapy to eliminate the factors that can potentially intensify the obstruction. Echocardiography is the basic modality in the diagnosis and treatment of left ventricular outflow tract obstruction. This paper presents four patients in whom the immediate implementation of bedside echocardiography enabled a rapid diagnosis of left ventricular outflow tract obstruction and implementation of proper treatment. PMID- 26674264 TI - Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10. AB - Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB. PMID- 26674266 TI - The status of temporomandibular and cervical spine education in credentialed orthopedic manual physical therapy fellowship programs: a comparison of didactic and clinical education exposure. AB - OBJECTIVE: The purpose of this investigation was to establish a baseline of physical therapist education on temporomandibular disorders (TMD)-related topics during credentialed orthopedic manual physical therapy fellowship training and compare it to cervical spine disorders education. METHOD: An online survey was distributed electronically to each fellowship program credentialed by the American Physical Therapy Association (APTA) and recognized by the Academy of Orthopedic Manual Physical Therapists (AAOMPT). Data were analyzed to compare overall exposure to TMD educational content, including a direct comparison of TMD and cervical spine disorders education. RESULTS: The response rate was 79%. Thirteen programs (87%) reported providing both didactic and clinical training on both TMD and cervical spine disorders. Didactic education for cervical spine disorders ranged from 16-20 hours to over 25 hours, whereas TMD hours ranged from 0 to 6-10 hours. Clinical education for cervical spine disorders ranged from 11 15 hours to over 25 hours, whereas TMD hours ranged from 0 to 6-10 hours. The number of hours of exposure during didactic training and the number of patients exposed to during clinical training were significantly different when comparing TMD to cervical spine disorders exposure (P<0.0001). DISCUSSION: The data indicate a lack of uniformity between credentialed fellowship programs in orthopedic manual physical therapy with respect to the extent to which programs expose trainees to evaluation and management of TMD. There is consistency in that all programs provided more training on cervical spine disorders than TMD. Despite a high level of clinical specialization, fellows-in-training receive minimal TMD education. PMID- 26674267 TI - A Life Course Approach to Inequality: Examining Racial/Ethnic Differences in the Relationship between Early Life Socioeconomic Conditions and Adult Health Among Men. AB - OBJECTIVE: Previous research has documented a relationship between childhood socioeconomic conditions and adult health, but less is known about racial/ethnic differences in this relationship, particularly among men. This study utilizes a life course approach to investigate racial/ethnic differences in the relationships among early and later life socioeconomic circumstances and health in adulthood among men. DESIGN: Panel data from the Health and Retirement Study and growth curve models are used to examine group differences in the relationships among childhood and adult socioeconomic factors and age trajectories of self-rated health among White, Black and Mexican American men aged 51-77 years (N=4147). RESULTS: Multiple measures of childhood socioeconomic status (SES) predict health in adulthood for White men, while significantly fewer measures of childhood SES predict health for Black and Mexican American men. Moreover, the health consequences of childhood SES diminish with age for Black and Mexican American men. The childhood SES-adult health relationship is largely explained by measures of adult SES for White men. CONCLUSIONS: The life course pathways linking childhood SES and adult health differ by race/ethnicity among men. Similar to arguments that the universality of the adult SES-health relationship should not be assumed, results from our study suggest that scholars should not assume that the significance and nature of the association between childhood SES and health in adulthood is similar across race/ethnicity among men. PMID- 26674268 TI - Prevention, Detection and Management of Coronary Artery Disease in Minority Females. AB - BACKGROUND AND SIGNIFICANCE: Heart disease is the leading cause of death for women living in the United States; this disease claims more female lives than all cancers combined. Additionally, according to the Centers of Disease Control data between the years 1979 and 2006, while cardiac-related mortality among men decreased significantly, only a modest decline was found among women. This disparity is greatest among minority females including Blacks and Hispanics who have an even greater prevalence of CVD and its risk factors. PREVENTION: There are several risk factors for coronary artery disease (CAD). Modifiable risk factors include: tobacco smoking, hypertension, diabetes, hyperlipidemia, obesity and physical inactivity. The prevention of CAD is grounded in decreasing or removing these modifiable risk factors. DETECTION: Accurately diagnosing CAD is dependent on an accurate assessment of the patient's pre-test probability to determine the best diagnostic approach to pursue. The patient's functional status, resting EKG and cardiac risk factors also assist in determining the best non-invasive cardiac test to pursue. MANAGEMENT: The goals and mainstay in the management of minority females with stable CAD includes surveillance for CAD symptoms, management of hypertension, diabetes mellitus and hyperlipidemia, as well as encouraging healthy habits. CONCLUSION: Heart disease remains the leading cause of death in minority females. Providers must be diligent to aggressively decrease patients' cardiovascular risk and, when patients do present with cardiovascular symptoms, providers must be aggressive in accurately diagnosing and treating these patients to decrease cardiac morbidity and mortality. PMID- 26674269 TI - Perihepatic lymphadenopathy in children with chronic viral hepatitis. PMID- 26674270 TI - Errors and mistakes in the ultrasound diagnosis of the pancreas. AB - The differential diagnosis of the focal lesions in the region of the pancreas is difficult due to the similarity of clinical and radiological pictures of neoplastic and non-neoplastic lesions. This paper presents the most common causes of errors in ultrasound diagnosis of pancreatic pathologies. Attention was paid to the errors resulting from the structural variants of the pancreas and those caused by the neighborhood of intestine, stomach and other organs or vessels. Moreover, the article presents mistakes in the interpretation of ultrasound images of normal pancreas as well as its inflammatory and neoplastic lesions. The errors and mistakes in question were divided into three categories: 1) mistakes related to the anatomical structure of the pancreas (anatomical variants, echostructure and echogenicity, course of the splenic artery); 2) mistakes related to anatomical structures localized in the vicinity of the pancreas (caudate lobe of the liver, other organs and intestinal loops surrounding the head of the pancreas, vessels and bile ducts, lymph nodes in the region of the pancreas or duodenal diverticula and tumors); 3) mistakes related to the pathologies of the pancreas (inflammatory and neoplastic lesions including differentiation between inflammatory tumors and malignant masses). In spite of the progress of imaging techniques, the differential diagnosis of focal solid lesions remains the prime problem of imaging examinations of the pancreas. The major aim of the ultrasound examination is early detection of pancreatic neoplasm. Improper performance of the examination or a failure to perform a repeated scan when the conditions for the assessment of the pancreas are not favorable or, what is worse, description of normal pancreas when it is not clearly and entirely visible, constitute errors. PMID- 26674271 TI - SLiMScape 3.x: a Cytoscape 3 app for discovery of Short Linear Motifs in protein interaction networks. AB - Short linear motifs (SLiMs) are small protein sequence patterns that mediate a large number of critical protein-protein interactions, involved in processes such as complex formation, signal transduction, localisation and stabilisation. SLiMs show rapid evolutionary dynamics and are frequently the targets of molecular mimicry by pathogens. Identifying enriched sequence patterns due to convergent evolution in non-homologous proteins has proven to be a successful strategy for computational SLiM prediction. Tools of the SLiMSuite package use this strategy, using a statistical model to identify SLiM enrichment based on the evolutionary relationships, amino acid composition and predicted disorder of the input proteins. The quality of input data is critical for successful SLiM prediction. Cytoscape provides a user-friendly, interactive environment to explore interaction networks and select proteins based on common features, such as shared interaction partners. SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery (SLiMFinder and QSLiMFinder) and identifying occurrences/enrichment of known SLiMs (SLiMProb) within this interactive framework. SLiMScape makes it easier to (1) generate high quality hypothesis driven datasets for these tools, and (2) visualise predicted SLiM occurrences within the context of the network. To generate new predictions, users can select nodes from a protein network or provide a set of Uniprot identifiers. SLiMProb also requires additional query motif input. Jobs are then run remotely on the SLiMSuite server ( http://rest.slimsuite.unsw.edu.au) for subsequent retrieval and visualisation. SLiMScape can also be used to retrieve and visualise results from jobs run directly on the server. SLiMScape and SLiMSuite are open source and freely available via GitHub under GNU licenses. PMID- 26674272 TI - WIDESPREAD MACULAR NEUROSENSORY DETACHMENT AFTER OCRIPLASMIN INTRAVITREAL INJECTION. AB - PURPOSE: To present the case of a patient with vitreomacular traction who experienced immediate severe acute complications after ocriplasmin intravitreal injection. METHODS: Case report. RESULTS: A 61-year-old woman with vitreomacular traction underwent ocriplasmin treatment. Within 24 hours after injection, she noticed severe reduction in visual acuity. Spectral domain optical coherence tomography revealed release of vitreous traction, together with widespread subretinal fluid and decreased reflectivity in the outer retina. Ten weeks after treatment, visual acuity improved, although below pretreatment levels, with partial reduction in subretinal fluid. CONCLUSION: Intravitreal ocriplasmin can produce acute visual acuity changes with widespread subretinal fluid and outer retinal ellipsoid zone hyporeflectivity on spectral domain optical coherence tomography. The overall acute and long-term safety profile of ocriplasmin remains unknown. PMID- 26674273 TI - CENTRAL VISUAL PHENOMENA AS CLUES TO VITREOMACULAR TRACTION IN PATIENTS WITH NORMAL FUNDUS OCULI. AB - PURPOSE: To report two cases where the primary visual complaints were central visual phenomena, with normal fundus biomicroscopy. METHODS: History and clinical examination, fundus autofluorescence, and spectral domain-optical coherence tomography. RESULTS: The authors report 2 patients, a 66-year-old woman and a 77 year-old woman, who complained of a central visual disturbance in one eye. Best corrected visual acuity was normal. Ophthalmoscopy in the first case was unremarkable and showed minimal retinal pigment epithelial mottling in Case 2. Spectral domain-optical coherence tomography revealed vitreomacular traction with foveal distortion in both eyes, associated with small cysts in the inner retinal layers and in one patient disruption of photoreceptors. CONCLUSION: Central visual phenomena are important clues for central vitreomacular traction, even in the presence of a normal fundus examination. The authors highlight the importance of performing spectral domain-optical coherence tomography evaluation in this setting before considering neurologic or systemic causes. PMID- 26674274 TI - TEMPORAL INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR A MACULAR HOLE PATIENT UNABLE TO MAINTAIN POSTOPERATIVE PRONE POSITIONING. AB - PURPOSE: To report the surgical technique and efficacy of the temporal inverted internal limiting membrane (ILM) flap technique for a patient with an idiopathic macular hole (MH) who is unable to maintain postoperative prone positioning. METHODS: Case report. RESULTS: A 73-year-old man with a Stage III MH in his left eye was scheduled to undergo surgery. Owing to his inability to maintain postoperative prone positioning for continuous placement of a transdermal bladder catheter after radical cystoprostatectomy to treat urinary bladder cancer, he underwent pars plana vitrectomy combined with the temporal inverted ILM flap technique and intraocular sulfur hexafluoride gas tamponade. The technique included ILM peeling at a temporal area of the macula to create one 2-disk diameter semicircular ILM flap and inversion of the ILM flap nasally to cover the MH. Optical coherence tomography showed that MH closure started from the top of the MH just beneath the covered ILM flap; the closure process gradually extended toward the bottom of the MH. The well-aligned fovea recovered in 5 weeks postoperatively. The visual acuity was 20/200 preoperatively and improved to 20/50 postoperatively. CONCLUSION: The temporal inverted ILM flap technique, a simple surgery to treat MHs, provides scaffolding for retinal gliosis and may facilitate bridge formation between the walls of the MH beneath the flap. The procedure may be a good option to achieve MH closure without postoperative prone positioning. PMID- 26674275 TI - MYCOBACTERIUM MANITOBENSE MASQUERADING AS CORYNEBACTERIUM PSEUDODIPHTHERITICUM IN A CASE OF POSTCATARACT SURGERY ENDOPHTHALMITIS. AB - PURPOSE: To describe a case of postoperative Mycobacterium manitobense endophthalmitis with good visual outcome that is the first report of endophthalmitis by this organism. METHODS: Clinical and microbiological description of a patient with postoperative endophthalmitis. RESULTS: A 50-year old chronic alcoholic man was referred to us with decreased vision in his right eye for 4 days. He had undergone cataract surgery with intraocular lens implantation in his right eye a month ago. The presenting vision in his right eye was counting fingers close to face. He was diagnosed as a case of postoperative endophthalmitis. Subsequently, the patient underwent pars plana vitrectomy and vitreous biopsy. The microbiologic investigation of the vitreous biopsy showed poorly stained gram-positive beaded bacilli that were acid fast, and growth in culture was identified as Corynebacterium pseudodiphtheriticum by Vitek 2 bacterial identification system. However, DNA analysis confirmed the organism to be M. manitobense. The patient responded well to repeat interventions with intravitreal antibiotics with a final reported visual acuity of 20/30 at 4 months after first intervention. CONCLUSION: Although known to be an organism causing soft-tissue infections, M. manitobense can also cause postsurgical endophthalmitis. The diagnosis can be confused with Corynebacterium sp. on smear and culture. Subsequent DNA sequencing of the culture provides definite identification of the organism. PMID- 26674276 TI - RETINAL CAVERNOUS HEMANGIOMA DOCUMENTED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AND CONFOCAL SCANNING LASER OPHTHALMOSCOPE RETRO-MODE IMAGING. AB - PURPOSE: To report a case of retinal cavernous hemangioma documented by spectral domain optical coherence tomography and retro-mode retinal imaging by confocal scanning laser ophthalmoscope. METHODS: Clinical examination, fluorescein angiography, spectral domain optical coherence tomography, and scanning laser ophthalmoscope retro-mode imaging were performed. RESULTS: Fundus examination of the left eye of an asymptomatic 39-year-old woman showed an irregularly elevated dark red lesion with a cluster of various-sized saccular aneurysms. The retinal cavernous hemangioma lesions were in the upper vascular arcade. A late-phase fluorescein angiography image showed a typical finding, known as fluorescence capping, characterized by incomplete perfusion because of plasma-erythrocyte separation, which was seen in some larger aneurysms. Spectral domain optical coherence tomography showed that various-sized dilated cystic spaces corresponded to the aneurysms. The image showed the horizontal line, which corresponded to the fluorescence capping in some larger aneurysms. Scanning laser ophthalmoscope retro-mode images showed the individual sizes and septum of the aneurysms. The image also showed the characteristic dots-and-lines pattern around the retinal cavernous hemangioma at the corresponding area of inner retinoschisis attributed to the aneurysms without outer retinoschisis on the spectral domain optical coherence tomography images. CONCLUSION: Spectral domain optical coherence tomography and scanning laser ophthalmoscope retro-mode imaging may be useful for evaluating the pathophysiologic features and the full extent of the retinal cavernous hemangioma. PMID- 26674277 TI - GRANULAR HYPERREFLECTIVE SPECKS BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AS SIGNS OF WEST NILE VIRUS INFECTION: THE STARDUST SIGN. AB - PURPOSE: To report the retinal findings and evolution of a visually symptomatic case of West Nile virus meningoencephalitis. METHODS: Case report. Main outcome measures include serologic testing for West Nile virus as well as longitudinal funduscopic examination, fluorescein angiography, and spectral domain optical coherence tomography. RESULTS: A 47-year-old diabetic man was referred for ophthalmic evaluation after hospitalization and treatment for West Nile meningoencephalitis. The patient presented with decreased vision and black spots in the right eye. Baseline visual acuity was 20/100 in the right eye and 20/40 in the left. Funduscopic examination and fluorescein angiography revealed multiple outer-retinal, punctate white spots in the macula and midperiphery of the right eye with no irregularities noted in the left eye. Spectral domain optical coherence tomography revealed granular hyperreflective specks casting variably dense shadows scattered throughout multiple retinal layers, most prominently within the outer and inner nuclear layers of the right eye. The patient was observed over the course of 14 weeks, and final visual acuity was 20/50 in the right eye. Longitudinally, the number of specks progressively decreased. CONCLUSION: During West Nile virus infection, granular hyperreflective specks located predominantly within the outer and inner nuclear layers were visualized by spectral domain optical coherence tomography and may be a sign of West Nile virus infection. PMID- 26674278 TI - SURGICAL EMBOLECTOMY FOR FOVEA-THREATENING ACUTE RETINAL ARTERY OCCLUSION. AB - PURPOSE: To describe a technique of surgical intraocular embolectomy in patients with acute fovea-threatening branch retinal artery occlusion. METHODS: Pars plana vitrectomy with embolectomy involving embolus isolation, dissection, and removal in patients with an acute fovea-threatening arterial occlusion without a patent cilioretinal artery. RESULTS: The surgical technique involves a core vitrectomy. The blocked artery is incised using a microvitreoretinal blade, and microsurgical forceps are used to retrieve the embolus. No significant complications were noted. The study technique offers an excellent safety profile and minimizes the risk of vitreous hemorrhage by carefully dissecting the vascular adventitial sheath and isolating the embolus. CONCLUSION: Surgical embolectomy is a viable technique for patients with acute fovea-threatening arterial occlusions without patent cilioretinal artery. Careful dissection and retrieval of the embolus minimizes the risk of vitreous hemorrhage, which is an important improvement in previous techniques for management of acute retinal arterial occlusions. PMID- 26674279 TI - The unique contributions of Professor Anton Amann to the field of breath research. PMID- 26674280 TI - Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses. AB - Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE) as IFN-alpha producers and promoters of T-cell activation or tolerance. Here, we demonstrated by flow-cytometry and confocal microscopy that Siglec-1, a molecule involved in the regulation of adaptive immunoresponses, is expressed in a subset of semi-mature, myeloid-like pDCs in human blood. These pDCs express lower BDCA-2 and CD123 and higher HLA-DR and CD11c than Siglec-1-negative pDCs and do not produce IFN-alpha via TLR7/TLR9 engagement. In vitro, Siglec-1 expression was induced in Siglec-1-negative pDCs by influenza virus. Proportions of Siglec-1-positive/Siglec-1-negative pDCs were higher in SLE than in healthy controls and correlated with disease activity. Healthy donors immunized with yellow fever vaccine YFV-17D displayed different kinetics of the two pDC subsets during protective immune response. PDCs can be subdivided into two subsets according to Siglec-1 expression. These subsets may play specific roles in (auto)immune responses. PMID- 26674281 TI - Cardiovascular sympathetic arousal in response to different mental stressors. AB - The altered regulation of autonomic response to mental stress can result in increased cardiovascular risk. The laboratory tests used to simulate the autonomic responses to real-life stressors do not necessarily induce generalized sympathetic activation; therefore, the assessment of regulatory outputs to different effector organs could be important. We aimed to study the cardiovascular sympathetic arousal in response to different mental stressors (Stroop test, mental arithmetic test) in 20 healthy students. The conceivable sympathetic vascular index--spectral power of low frequency band of systolic arterial pressure variability (LF-SAP) and novel potential cardio-sympathetic index--symbolic dynamics heart rate variability index 0V% were evaluated. The heart and vessels responded differently to mental stress--while Stroop test induced increase of both 0V% and LF-SAP indices suggesting complex sympathetic arousal, mental arithmetic test evoked only 0V% increase compared to baseline (p<0.01, p<0.001, p<0.01, respectively). Significantly greater reactivity of LF SAP, 0V%, heart rate (HR) and mean arterial pressure (MAP) were found in response to Stroop test compared to mental arithmetic test potentially indicating the effect of different central processing (0V%, LF-SAP: p<0.001; HR, MAP: p<0.01). The different effectors' sympathetic responses to cognitive stressors could provide novel important information regarding potential pathomechanisms of stress related diseases. PMID- 26674282 TI - Participation of heart mitochondria in myocardial protection against ischemia/reperfusion injury: benefit effects of short-term adaptation processes. AB - Acute streptozotocin diabetes mellitus (DM) as well as remote ischemic preconditioning (RPC) has shown a favorable effect on the postischemic reperfusion function of the myocardium. Cardioprotective mechanisms offered by these experimental models involve the mitochondria with the changes in functional properties of membrane as the end-effector. The aim was to find out whether separate effects of RPC and DM would stimulate the mechanisms of cardioprotection to a maximal level or whether RPC and DM conditions would cooperate in stimulation of cardioprotection. Experiments were performed on male Wistar rats divided into groups: control, DM, RPC and DM treated by RPC (RPC+DM). RPC protocol of 3 cycles of 5-min hind limb ischemia followed by 5-min reperfusion was used. Ischemic-reperfusion injury was induced by 30-min ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Mitochondria were isolated by differential centrifugation, infarct size assessed by staining with 1 % 2,3,5 triphenyltetrazolium chloride, mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ(9) and CoQ(10) with HPLC. Results revealed that RPC as well as DM decreased the infarct size and preserved mitochondrial function by increasing the mitochondrial membrane fluidity. Both used models separately offered a sufficient protection against ischemic-reperfusion injury without an additive effect of their combination. PMID- 26674283 TI - The effect of alpha-tocopheryl succinate on succinate respiration in rat liver mitochondria. AB - We compared the effect of alpha-tocopheryl succinate (TOS) on succinate-dependent respiration in rat liver mitochondria, homogenate and permeabilized hepatocytes in both a coupled and uncoupled state. In isolated mitochondria, a significant inhibitory effect was observed at a concentration of 5 microM, in liver homogenate at 25 microM and in permeabilized hepatocytes at 50 microM. The inhibitory effect of TOS on succinate respiration in an uncoupled state was less pronounced than in a coupled state in all the experimental models tested. When the concentration dependence of the TOS inhibitory effect was tested, the most sensitive in both states were isolated mitochondria; the most resistant were permeabilized hepatocytes. PMID- 26674284 TI - Signs of myelin impairment in cerebrospinal fluid after osmotic opening of the blood-brain barrier in rats. AB - A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons. PMID- 26674285 TI - Testosterone in relation to behavioral problems in pre-pubertal boys with autism spectrum disorders. AB - Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impairment in social communication and presence of stereotyped/restricted behaviors. Children with ASD very often demonstrate co-morbid psychiatric problems, problems known to be affected by testosterone in neurotypical populations. However, there are few reports investigating relationships between testosterone and psychiatric conditions in children with ASD. The aim of this study was to determine the relationship between plasmatic levels of testosterone and behavioral/emotional problems in pre-pubertal boys with ASD. The study sample consisted of 31 pre-pubertal boys (ages 3-10) with ASD. Parents completed the Nisonger Child Behavior Rating Form (NCBRF) to assess specific behavioral/emotional problems as observed in the previous 2 months. Plasmatic testosterone levels were determined in boys according to standardized procedures. It was found that there were positive correlations between testosterone levels and the conduct problems subscale (p=0.034, rs=0.382) of NCBRF and also between testosterone levels and the hyperactive subscale (p=0.025, rs=0.402) of NCBRF. Findings in this study are in line with research conducted in the neurotypical population. This is the first large study investigating testosterone and emotional/behavioral problems in ASD and warrants further research in this field in order to clarify the etiopathogenesis of psychiatric co-morbidities and improve their treatment. PMID- 26674286 TI - Effect of maturation on the resistance of rat hearts against ischemia. Study of potential molecular mechanisms. AB - Reduced tolerance to ischemia/reperfusion (IR) injury has been shown in elder human and animal hearts, however, the onset of this unfavorable phenotype and cellular mechanisms behind remain unknown. Moreover, aging may interfere with the mechanisms of innate cardioprotection (preconditioning, PC) and cause defects in protective cell signaling. We studied the changes in myocardial function and response to ischemia, as well as selected proteins involved in "pro-survival" pathways in the hearts from juvenile (1.5 months), younger adult (3 months) and mature adult (6 months) male Wistar rats. In Langendorff-perfused hearts exposed to 30-min ischemia/2-h reperfusion with or without prior PC (one cycle of 5-min ischemia/5-min reperfusion), we measured occurrence of reperfusion-induced arrhythmias, recovery of contractile function (left ventricular developed pressure, LVDP, in % of pre-ischemic values), and size of infarction (IS, in % of area at risk size, TTC staining and computerized planimetry). In parallel groups, LV tissue was sampled for the detection of protein levels (WB) of Akt kinase (an effector of PI3-kinase), phosphorylated (activated) Akt (p-Akt), its target endothelial NO synthase (eNOS) and protein kinase Cepsilon (PKCepsilon) as components of "pro-survival" cascades. Maturation did not affect heart function, however, it impaired cardiac response to lethal IR injury (increased IS) and promoted arrhythmogenesis. PC reduced the occurrence of malignant arrhythmias, IS and improved LVDP recovery in the younger animals, while its efficacy was attenuated in the mature adults. Loss of PC protection was associated with age dependent reduced Akt phosphorylation and levels of eNOS and PKCepsilon in the hearts of mature animals compared with the younger ones, as well as with a failure of PC to upregulate these proteins. Aging-related alterations in myocardial response to ischemia may be caused by dysfunction of proteins involved in protective cell signaling that may occur already during the process of maturation. PMID- 26674287 TI - Different doxorubicin formulations affect plasma 4-hydroxy-2-nonenal and gene expression of aldehyde dehydrogenase 3A1 and thioredoxin reductase 2 in rat. AB - Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin. PMID- 26674288 TI - The effect of oleic and palmitic acid on induction of steatosis and cytotoxicity on rat hepatocytes in primary culture. AB - In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5 1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production. OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone. In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone. PMID- 26674289 TI - The effect of D-galactosamine on lean and steatotic rat hepatocytes in primary culture. AB - The aim of our work was to compare the effect of D-galactosamine (GalN) on primary cultures of lean and steatotic rat hepatocytes isolated from intact and fatty liver, respectively. GalN caused more severe injury to steatotic hepatocytes than to lean cells as documented by lactate dehydrogenase leakage. Necrotic mode of cell death strongly prevails over apoptosis since we did not observe any significant increase in activities of caspase 3, 8 and 9 in any group of hepatocytes treated with GalN. Reactive oxygen species (ROS) formation and lipid peroxidation were elevated in a dose-dependent manner by GalN and were significantly more pronounced in fatty hepatocytes. A decrease in the percentage of hepatocytes with energized mitochondria was observed from 30 mM and 10 mM GalN in lean and steatotic hepatocytes, respectively. Our results undoubtedly indicate that steatotic hepatocytes exert higher sensitivity to the toxic effect of GalN. This sensitivity may be caused by more intensive GalN-induced ROS production and lipid peroxidation and by higher susceptibility of mitochondria to loss of mitochondrial membrane potential in steatotic hepatocytes. In our experimental arrangement, apoptosis does not seem to participate considerably on hepatotoxic action of GalN in either group of hepatocytes. PMID- 26674290 TI - Heart rate variability and inflammatory response in rats with lipopolysaccharide induced endotoxemia. AB - The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS) induced endotoxemia. Animals were injected intraperitoneally with LPS (100 microg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low (LF) and high frequency (HF) bands. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2+/-0.5 vs. 1.9+/-0.6 ms(2), P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0+/-0.6 vs. 26.4+/-4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia. PMID- 26674291 TI - Use of electrogastrography in preclinical studies of cholinergic and anticholinergic agents in experimental pigs. AB - Electrogastrography (EGG) is a non-invasive method for the assessment of gastric myoelectrical activity. Porcine EGG is comparable with human one. The purpose of this study was to evaluate the effect of atropine and neostigmine on the EGG in experimental pigs. Adult female pigs were administrated atropine (1.5 mg i.m., n=6) and neostigmine (0.5 mg i.m., n=6) after the baseline EGG, followed by a 90 min trial recording (MMS, Enschede, the Netherlands). Running spectral analysis was used for the evaluation. The results were expressed as dominant frequency of slow waves and EGG power (areas of amplitudes). Neostigmine increased continuously the dominant frequency and decreased significantly the EGG power. Atropine did not change the dominant frequency significantly. However, atropine increased significantly the EGG power (areas of amplitudes) from basal values to the maximum at the 10-20-min interval. After that period, the areas of amplitudes decreased significantly to the lowest values at the 60-90-min interval. In conclusion, cholinergic and anticholinergic agents affect differently EGG in experimental pigs. PMID- 26674292 TI - The development of selected cardiovascular parameters in patients with type 2 diabetes mellitus during a spa treatment. AB - Diabetes mellitus is not just a simple metabolic disorder, however, it is considered to be a cardiovascular disease of a metabolic origin. This is apparent especially when speaking about type 2 diabetes (DM II). The objective of our study was to determine whether a comprehensive spa treatment (procedures and drinking cure) may affect the level of the sympathetic tone of patients suffering from DM II. As an indicator of the sympathetic tone, selected electrocardiographic parameters derived from the heart rate variability and microwave alternans were chosen. There were 96 patients enrolled in our study: 38 patients with poorly controlled DM II and two control groups: 9 patients with compensated DM II and 49 patients, average age without diabetes or other disorders of the glucose metabolism. All received an identical spa treatment and continued their medical therapy. The electrophysiological examination of patients was performed before and after a three-week spa treatment using the KARDiVAR system. Parameters derived from the analysis of heart rate variability (HRV), microvolt T-wave alternans, and microvolt R-wave alternans were analyzed in order to evaluate the tones of the autonomic nervous system (ANS). The control group showed a slight increase of parameter the index of activity of regulatory systems (IRSA) (4.4+/-1.3 vs. 3.8+/-1.4; p=0.006) after the spa treatment, while increased heart rate (80.9+/-11.0 vs. 74.6+/-9.6; p=0.028), reduced index of centralization (IC) (1.3+/-0.6 vs. 2.9+/-1.4; p=0.027) and reduced index of myocardium (IM) (9.9+/-7.4 vs. 18.0+/-6.3; p=0.041) were found in patients with a compensated DM II. Patients with a poorly compensated DM II showed a decreased IM (10.9+/-8.6 vs. 16.9+/-5.2; p=0.001) and also a reduced IRSA (4.1+/-3.5 vs. 6.3+/ 1.9; p=0.001). The results proved favorable changes in ANS cardiovascular control of patients with DM II after a spa treatment, especially in terms of reducing the sympathoadrenal system activity (decreased IRSA), improving electrical stability of the myocardium and increasing centrally controlled heart rate variability without overloading the cardiovascular system (drop of IM). PMID- 26674293 TI - Head-up tilt rapidly compromises hemodynamics in healthy anesthetized swine. AB - The aims were to explore the effect of head-up tilt (HUT) to 30 and 60 degrees on hemodynamics and tissue oxygenation in anesthetized healthy swine. The data serve as a reference for a study of resuscitation efficacy at HUT such as during transport. Nine healthy swine (49+/-4 kg) were anesthetized and multiple sensors including myocardial pressure-volume loops catheter, carotid flow probe, blood pressure catheters, near infrared spectroscopy (NIRS) tissue oximetry and mixed venous oximetry (SVO2) catheter were introduced and parameters continuously recorded. Experimental protocol consisted of baseline in supine position (15 min), 30 degrees HUT (15 min), recovery at supine position (15 min) and 60 degrees HUT (5 min). Vacuum mattress was used for body fixation during tilts. We found that 30 and 60 degrees inclination led to significant immediate reduction in hemodynamic and oximetry parameters. Mean arterial pressure (mm Hg) decreased from 98 at baseline to 53 and 39, respectively. Carotid blood flow dropped to 47 % and 22 % of baseline values, end diastolic volume to 49 % and 53 % and stroke volume to 47 % and 45 % of baseline. SVO2 and tissue oximetry decreased by 17 and 21 percentage points. The values are means. In conclusions, within minutes, both 30 and 60 degrees head-up tilting is poorly tolerated in anesthetized swine. Significant differences among individual animals exist. PMID- 26674294 TI - Electrocardiographic changes in diabetes mellitus. AB - Diabetes mellitus (DM) has been known for many years to be associated with poor cardiovascular prognosis. Due to the sensitive neuropathy, the coronary artery disease in diabetic patients is frequently asymptomatic. Also twelve leads resting ECG can be within normal limits even in an advanced stage of coronary artery disease. Therefore in addition to the standard ECG other electrocardiographic procedures started to be studied in order to find some typical signs of myocardial damages caused by DM. Repeatedly reported results showed in DM patients without cardiovascular complications the tachycardia, shortening of the QRS and QT intervals, increase of the dispersion of QT interval, decreased amplitudes of depolarization waves, shortened activation time of ventricular myocardium and a flattening of T waves confirmed by the lower value of maximum and minimum in repolarization body surface isopotential maps. Most of these changes are even more pronounced in patients with cardiac autonomic neuropathy. Comparison with similar ECG changes in other diseases suggests that the electrocardiographic changes in DM patients are not specific and that they are particularly caused by an increased tone of the sympathetic nervous system what was indirectly confirmed by the heart rate variability findings in these patients. PMID- 26674295 TI - Jan Evangelista Purkyne and the cerebellum then and now. AB - The name of Jan Evangelista Purkyne and the cerebellum belong inseparably together. He was the first who saw and described the largest nerve cells in the brain, de facto in the cerebellum. The most distinguished researchers of the nervous system then showed him the highest recognition by naming these neurons as Purkinje cells. Through experiments by J. E. Purkyne and his followers properly functionally was attributed to the cerebellum share in precision of motor skills. Despite ongoing and fruitful research, after a relatively long time, especially in the last two decades, scientists had to constantly replenish and re-evaluate the traditional conception of the cerebellum and formulate a new one. It started in the early 1990s, when it was found that cerebellar cortex contains more neurons than the cerebral cortex. Shortly thereafter it was gradually revealed that such enormous numbers of neural cells are not without an impact on brain functions and that the cerebellum, except its traditional role in the motor skills, also participates in higher nervous activity. These new findings were obtained thanks to the introduction of modern methods of examination into the clinical praxis, and experimental procedures using animal models of cerebellar disorders described below. PMID- 26674296 TI - Kinetic and isotherm error optimization studies for adsorption of atrazine and imidacloprid on bark of Eucalyptus tereticornis L. AB - The aim of this study was to establish the bark of Eucalyptus tereticornis L. (EB) as a low cost bio-adsorbent for the removal of imidacloprid and atrazine from aqueous medium. The pseudo-first-order (PFO), pseudo-second-order (PSO), Elovich and intra-particle diffusion (IPD) models were used to describe the kinetic data and rate constants were evaluated. Adsorption data was analysed using ten 2-, 3- and 4-parameter models viz. Freundlich, Jovanovic, Langmuir, Temkin, Koble-Corrigan, Redlich-Peterson, Sips, Toth, Radke-Prausnitz, and Fritz Schluender isotherms. Six error functions were used to compute the best fit single component isotherm parameters by nonlinear regression analysis. The results showed that the sorption of atrazine was better explained by PSO model, whereas the sorption of imidacloprid followed the PFO kinetic model. Isotherm model optimization analysis suggested that the Freundlich along with Koble Corrigan, Toth and Fritz-Schluender were the best models to predict atrazine and imidacloprid adsorption onto EB. Error analysis suggested that minimization of chi-square (chi(2)) error function provided the best determination of optimum parameter sets for all the isotherms. PMID- 26674297 TI - Providing surgery in a war-torn context: the Medecins Sans Frontieres experience in Syria. AB - BACKGROUND: Since 2011, civil war has crippled Syria leaving much of the population without access to healthcare. Various field hospitals have been clandestinely set up to provide basic healthcare but few have been able to provide quality surgical care. In 2012, Medecins Sans Frontieres (MSF) began providing surgical care in the Jabal al-Akrad region of north-western Syria. Based on the MSF experience, we describe, for the period 5th September 2012 to 1st January 2014: a) the volume and profile of surgical cases, b) the volume and type of anaesthetic and surgical procedures performed, and c) the intraoperative mortality rate. METHODS: A descriptive study using routinely collected MSF programme data. Quality surgical care was assured through strict adherence to the following minimum standards: adequate infrastructure, adequate water and sanitation provisions, availability of all essential disposables, drugs and equipment, strict adherence to hygiene requirements and universal precautions, mandatory use of sterile equipment for surgical and anaesthesia procedures, capability for blood transfusion and adequate human resources. RESULTS: During the study period, MSF operated on 578 new patients, of whom 57 % were male and median age was 25 years (Interquartile range: 21-32 years). Violent trauma was the most common surgical indication (n-254, 44 %), followed by obstetric emergencies (n-191, 33 %) and accidental trauma (n-59, 10 %). In total, 712 anaesthetic procedures were performed. General anaesthesia without intubation was the most common type of anaesthesia (47 % of all anaesthetics) followed by spinal anaesthesia (25 %). A total of 831 surgical procedures were performed, just over half being minor/wound care procedures and nearly one fifth, caesarean sections. There were four intra-operative deaths, giving an intra-operative mortality rate of 0.7 %. CONCLUSIONS: Surgical needs in a conflict-afflicted setting like Syria are high and include both combat and non-combat indications, particularly obstetric emergencies. Provision of quality surgical care in a complex and volatile setting like this is possible providing appropriate measures, supported by highly experienced staff, can be implemented that allow a specific set of minimum standards of care to be adhered to. This is particularly important when patient outcomes - as a reflection of quality of care - are difficult to assess. PMID- 26674298 TI - Classical and semiclassical dynamics in statistical environments with a mixed dynamical and statistical representation. AB - We present a basic theory to study real-time dynamics embedded in a large environment that is treated using a statistical method. In light of great progress in the molecular-level studies on time-resolved spectroscopies, chemical reaction dynamics, and so on, not only in the gas phase but also in condensed phases like liquid solvents and even in crowded environments in living cells, we need to bridge over a gap between statistical mechanics and microscopic real-time dynamics. For instance, an analogy to gas-phase dynamics in which molecules are driven by the gradient of the potential energy hyper-surfaces (PESs) suggests that particles in condensed phases should run on the free energy surface instead. The question is whether this anticipation is correct. To answer it, we here propose a mixed dynamics and statistical representation to treat chemical dynamics embedded in a statistical ensemble. We first define the entropy functional, which is a function of the phase-space position of the dynamical subsystem, being dressed with statistical weights from the statistical counterpart. We then consider the functionals of temperature, free energy, and chemical potential as their extensions in statistical mechanics, through which one can clarify the relationship between real-time microscopic dynamics and statistical quantities. As an illustrative example we show that molecules in the dynamical subsystem should run on the free-energy functional surface, if and only if the spatial gradients of the temperature functional are all zero. Otherwise, additional forces emerge from the gradient of the temperature functional. Numerical demonstrations are presented at the very basic level of this theory of molecular dissociation in atomic cluster solvents. PMID- 26674300 TI - TEMPORAL PATTERN OF KINESIOLOGY TAPE EFFICACY ON HAMSTRING EXTENSIBILITY. AB - BACKGROUND: Kinesiology tape has been advocated as a means of improving muscle flexibility, a potential modifiable risk factor for injury, over time. The epidemiology and etiology of hamstring injuries in sport have been well documented. PURPOSE: To compare the temporal pattern of efficacy of kinesiology tape and traditional stretching techniques on hamstring extensibility over a five day period. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty recreationally active male participants (Mean +/- SD: age 20.0 +/- 1.55 years; height 179.3 +/- 4.94 cm; mass 76.9 +/- 7.57 kg) completed an active knee extension assessment (of the dominant leg) as a measure of hamstring extensibility. Three experimental interventions were applied in randomized order: Kinesiology tape (KT), static stretch (SS), proprioceptive neuromuscular facilitation (PNF). Measures were taken at baseline, +1min, + 30mins, + 3days and +5days days after each intervention. The temporal pattern of change in active knee extension was modelled as a range of regression polynomials for each intervention, quantified as the regression coefficient. RESULTS: Hamstring ROM with KT application at +3days was significantly greater than baseline (129.18 +/- 15.46%, p = 0.01), SS (106.99 +/- 9.84%, p = 0.03) and PNF (107.42 +/- 136.13%, p = 0.03) interventions. The temporal pattern of changes in ROM for SS and PNF were best modelled by a negative linear function, although the strength of the correlation was weak in each case. In contrast, the KT data was optimised using a quadratic polynomial function (r(2) = 0.60), which yielded an optimum time of 2.76 days, eliciting a predicted ROM of 129.6% relative to baseline. CONCLUSION: Each intervention displayed a unique temporal pattern of changes in active knee extension. SS was best suited to immediate improvements, and PNF to +30 minutes in hamstring extensibility, whereas kinesiology tape offered advantages over a longer duration, peaking at 2.76 days. These findings have implications for the choice of intervention, timing and duration to assist clinicians in both a sporting and clinical context. LEVEL OF EVIDENCE: 2c. PMID- 26674299 TI - Alternating current electrohydrodynamics in microsystems: Pushing biomolecules and cells around on surfaces. AB - Electrohydrodynamics (EHD) deals with the fluid motion induced by an electric field. This phenomenon originally developed in physical science, and engineering is currently experiencing a renaissance in microfluidics. Investigations by Taylor on Gilbert's theory proposed in 1600 have evolved to include multiple contributions including the promising effects arising from electric field interactions with cells and particles to influence their behaviour on electrode surfaces. Theoretical modelling of electric fields in microsystems and the ability to determine shear forces have certainly reached an advanced state. The ability to deftly manipulate microscopic fluid flow in bulk fluid and at solid/liquid interfaces has enabled the controlled assembly, coagulation, or removal of microstructures, nanostructures, cells, and molecules on surfaces. Furthermore, the ability of electrohydrodynamics to generate fluid flow using surface shear forces generated within nanometers from the surface and their application in bioassays has led to recent advancements in biomolecule, vesicle and cellular detection across different length scales. With the integration of Alternating Current Electrohydrodynamics (AC-EHD) in cellular and molecular assays proving to be highly fruitful, challenges still remain with respect to understanding the discrepancies between each of the associated ac-induced fluid flow phenomena, extending their utility towards clinical diagnostic development, and utilising them in tandem as a standard tool for disease monitoring. In this regard, this article will review the history of electrohydrodynamics, followed by some of the recent developments in the field including a new dimension of electrohydrodynamics that deals with the utilization of surface shear forces for the manipulation of biological cells or molecules on electrode surfaces. Recent advances and challenges in the use of electrohydrodynamic forces such as dielectrophoresis and ac electrosmosis for the detection of biological analytes are also reviewed. Additionally, the fundamental mechanisms of fluid flow using electrohydrodynamics forces, which are still evolving, are reviewed. Challenges and future directions are discussed from the perspective of both fundamental understanding and potential applications of these nanoscaled shear forces in diagnostics. PMID- 26674301 TI - Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part II: Inflammatory background of osteoarthritis. AB - Osteoarthritis is the most common rheumatoid disease. It may develop as a primary disease of the motor organ or as a secondary one in the course of other inflammatory joint diseases. Similarly to the majority of rheumatoid conditions, the pathogenesis of osteoarthritis has not been fully explained. The fact that its development is determined by adipocytokines, which are inflammatory mediators produced in the adipose tissue, has been known for several years. Additionally, inflammatory processes taking place in the adipose tissue that lead to degenerative changes are the main subject of studies conducted by various immunological laboratories. Degenerative changes in patients with osteoarthritis are frequently accompanied by secondary inflammation with cellular infiltrations in the synovial membrane. In numerous cases, the intensification of inflammatory lesions resembles changes seen in arthritis, particularly in rheumatoid arthritis, which inhibits the differential diagnosis by means of imaging examinations. This may have significant clinical implications, e.g. with respect to sonography, which is the basic imaging examination in diagnosing rheumatoid arthritis, monitoring the efficacy of implemented treatment or confirming remission. This article discusses the pathogenesis of three elements of osteoarthritis, i.e. synovitis (due to the difficulties in differentiation of synovitis in the course of osteoarthritis and in rheumatoid arthritis) as well as osteophytes and subchondral sclerosis (due to the significance of the inflammatory factor in their development). PMID- 26674302 TI - Comorbidities and pharmacotherapies in patients with Gaucher disease type 1: The potential for drug-drug interactions. AB - PURPOSE: Clinical care for patients with rare diseases may be complicated by comorbidities. Administration of medications to treat comorbidities may elicit potentially harmful drug-drug interactions (DDIs). Genetic background may also influence DDI occurrence. We investigated the range of comorbid conditions in patients with Gaucher disease type I (GD1), the pharmacotherapies prescribed and the potential for DDI with enzyme replacement and substrate reduction therapies and additional medications, specifically cytochrome P450 (CYP) metabolizing medications. METHODS: A literature review examined comorbid conditions and pharmacotherapies reported in GD1. Analysis of two national databases reported real-world prescription practices in patients with GD1 (Germany, N=87; US, N=374). Prescribed drugs were assessed for known interactions with isoenzymes from the hepatic CYP enzyme family. RESULTS: The literature reported GD1 symptomatology and comorbid conditions in broad agreement with the known clinical picture. German patients received 86 different medications whereas US patients received 329 different medications. An average of 3.2 medications (Germany) and 7 medications (US) per patient were prescribed. Moderate/strong inhibitors of CYP isoenzymes were prescribed to 20% and 57% of patients in the US and Germany, respectively. CONCLUSION: This study describes the extensive number of comorbid conditions and drugs prescribed to patients with GD1, and the importance of determining CYP isoenzyme interaction to reduce DDI risk. PMID- 26674303 TI - Acute Phase Proteins and Their Role in Periodontitis: A Review. AB - Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-alpha and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID- 26674304 TI - Conventional and Advanced Lipid Parameters in Premature Coronary Artery Disease Patients in India. AB - BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide and has assumed alarming proportions in India with gradual increase in its incidence and prevalence over the last decade. India is in the middle of epidemic of coronary artery disease which is leading cause of hospital admissions, morbidity and mortality. In the Indian population, there is higher tendency to develop CAD at a younger age, which cannot be explained on the basis of conventional lipid parameters. AIM: The purpose of this study is to find advanced lipid parameters which correlate better with premature CAD, as compared to the conventional lipid parameters. MATERIALS AND METHODS: Thirty middle aged individuals suffering from premature CAD and 30 age and gender matched healthy individuals without any history of clinical evidence suggestive of CAD were studied. Fasting venous blood samples of all the subjects under study were collected after an overnight fasting and conventional lipid parameters and advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) were estimated. Correlation of conventional and advanced lipid parameters with premature CAD and among each other was calculated using Pearson correlation coefficient. RESULTS: In our study the values of ox-LDL, sdLDL, Lp (a) and ApoB, total cholesterol, TG, LDL-C were significantly higher while HDL-C and Apo A1 and were significantly lower in cases than in controls. Advanced lipid parameters have higher correlation with premature CAD as compared to conventional lipid parameters. Ox-LDL show the highest correlation coefficient (r=+0.89) among these parameters followed by Lp (a) (r=+0.86) and ApoB (r=+0.79). CONCLUSION: Advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) are better discriminator of premature CAD as compared to conventional lipid parameters (total cholesterol, triglycerides, low density lipoprotein and high density lipoprotein). Oxidised LDL, small dense LDL and lipoprotein (a) can explain occurrence of CAD in normolipidemic patients and proved to be better markers for explaining high degree of prematurity, morbidity and mortality of CAD in Indian population. They can prove to be better marker for early detection and intervention in premature CAD and site for targeted drug therapy. PMID- 26674305 TI - Serial Magnetic Resonance Imaging in Active Surveillance of Prostate Cancer: Incremental Value. AB - PURPOSE: We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. MATERIALS AND METHODS: A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model. RESULTS: The mean interval between baseline and followup multiparametric magnetic resonance imaging was 28.3 months (range 11 to 43). Pathological progression occurred in 19 patients (39%). The sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging was 37%, 90%, 69% and 70%, respectively. Area under the receiver operating characteristic curve was 0.63. A logistic regression model using clinical information (maximum cancer core length greater than 3 mm on baseline biopsy or a prostate specific antigen density greater than 0.15 ng/ml(2) at followup biopsy) had an AUC of 0.87 for predicting pathological progression. The addition of serial multiparametric magnetic resonance imaging data significantly improved the AUC to 0.91 (p=0.044). CONCLUSIONS: Serial multiparametric magnetic resonance imaging adds incremental value to prostate specific antigen density and baseline cancer core length for predicting Gleason 6 upgrading in men on active surveillance. PMID- 26674306 TI - Metabolomics of dates (Phoenix dactylifera) reveals a highly dynamic ripening process accounting for major variation in fruit composition. AB - BACKGROUND: Dates are tropical fruits with appreciable nutritional value. Previous attempts at global metabolic characterization of the date metabolome were constrained by small sample size and limited geographical sampling. In this study, two independent large cohorts of mature dates exhibiting substantial diversity in origin, varieties and fruit processing conditions were measured by metabolomics techniques in order to identify major determinants of the fruit metabolome. RESULTS: Multivariate analysis revealed a first principal component (PC1) significantly associated with the dates' countries of production. The availability of a smaller dataset featuring immature dates from different development stages served to build a model of the ripening process in dates, which helped reveal a strong ripening signature in PC1. Analysis revealed enrichment in the dry type of dates amongst fruits with early ripening profiles at one end of PC1 as oppose to an overrepresentation of the soft type of dates with late ripening profiles at the other end of PC1. Dry dates are typical to the North African region whilst soft dates are more popular in the Gulf region, which partly explains the observed association between PC1 and geography. Analysis of the loading values, expressing metabolite correlation levels with PC1, revealed enrichment patterns of a comprehensive range of metabolite classes along PC1. Three distinct metabolic phases corresponding to known stages of date ripening were observed: An early phase enriched in regulatory hormones, amines and polyamines, energy production, tannins, sucrose and anti-oxidant activity, a second phase with on-going phenylpropanoid secondary metabolism, gene expression and phospholipid metabolism and a late phase with marked sugar dehydration activity and degradation reactions leading to increased volatile synthesis. CONCLUSIONS: These data indicate the importance of date ripening as a main driver of variation in the date metabolome responsible for their diverse nutritional and economical values. The biochemistry of the ripening process in dates is consistent with other fruits but natural dryness may prevent degenerative senescence in dates following ripening. Based on the finding that mature dates present varying extents of ripening, our survey of the date metabolome essentially revealed snapshots of interchanging metabolic states during ripening empowering an in-depth characterization of underlying biology. PMID- 26674307 TI - Environmental Effects of BPA: Focus on Aquatic Species. AB - Research on bisphenol A (BPA) as an environmental contaminant has now major regulatory implications toward the ecosystem health, and hence it is incumbent on scientists to do their research to the highest standards possible, in order that the most appropriate decisions are made to mitigate the impacts to aquatic wildlife. However, the contribution given so far appears rather fragmented. The present overview aims to collect available information on the effects of BPA on aquatic vertebrates and invertebrates to provide a general scenario and to suggest future developments toward more comprehensive approaches useful for aquatic species protection. PMID- 26674308 TI - RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression. AB - Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry. PMID- 26674310 TI - Endocardial-to-mesenchymal transformation and mesenchymal cell colonization at the onset of human cardiac valve development. AB - The elucidation of mechanisms in semilunar valve development might enable the development of new therapies for congenital heart disorders. Here, we found differences in proliferation-associated genes and genes repressed by VEGF between human semilunar valve leaflets from first and second trimester hearts. The proliferation of valve interstitial cells and ventricular valve endothelial cells (VECs) and cellular density declined from the first to the second trimester. Cytoplasmic expression of NFATC1 was detected in VECs (4 weeks) and, later, cells in the leaflet/annulus junction mesenchyme expressing inactive NFATC1 (5.5-9 weeks) were detected, indicative of endocardial-to-mesenchymal transformation (EndMT) in valvulogenesis. At this leaflet/annulus junction, CD44(+) cells clustered during elongation (11 weeks), extending toward the tip along the fibrosal layer in second trimester leaflets. Differing patterns of maturation in the fibrosa and ventricularis were detected via increased fibrosal periostin content, which tracked the presence of the CD44(+) cells in the second trimester. We revealed that spatiotemporal NFATC1 expression actively regulates EndMT during human valvulogenesis, as early as 4 weeks. Additionally, CD44(+) cells play a role in leaflet maturation toward the trilaminar structure, possibly via migration of VECs undergoing EndMT, which subsequently ascend from the leaflet/annulus junction. PMID- 26674309 TI - Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix. AB - The enteric nervous system (ENS) develops from neural crest cells that migrate along the intestine, differentiate into neurons and glia, and pattern into two plexuses within the gut wall. Inductive interactions between epithelium and mesenchyme regulate gut development, but the influence of these interactions on ENS development is unknown. Epithelial-mesenchymal recombinations were constructed using avian hindgut mesenchyme and non-intestinal epithelium from the bursa of Fabricius. These recombinations led to abnormally large and ectopically positioned ganglia. We hypothesized that sonic hedgehog (Shh), a secreted intestinal epithelial protein not expressed in the bursa, mediates this effect. Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in large, ectopic ganglia adjacent to the epithelium. Shh overexpression, achieved in ovo using Shh-encoding retrovirus and in organ culture using recombinant protein, led to intestinal aganglionosis. Shh strongly induced the expression of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulfate proteoglycans that are known to be inhibitory to neural crest cell migration. Shh also inhibited enteric neural crest-derived cell (ENCC) proliferation, promoted neuronal differentiation, and reduced expression of Gdnf, a key regulator of ENS formation. Ptc1 and Ptc2 were not expressed by ENCCs, and migration of isolated ENCCs was not inhibited by Shh protein. These results suggest that epithelial-derived Shh acts indirectly on the developing ENS by regulating the composition of the intestinal microenvironment. PMID- 26674312 TI - Prevascularization in tissue engineering: Current concepts and future directions. AB - The survival of engineered tissue constructs during the initial phase after their implantation depends on the rapid development of an adequate vascularization. This, in turn, is a major prerequisite for the constructs' long-term function. 'Prevascularization' has emerged as a promising concept in tissue engineering, aiming at the generation of a preformed microvasculature in tissue constructs prior to their implantation. This should shorten the time period during which the constructs are avascular and suffer hypoxic conditions. Herein, we provide an overview of current strategies for the generation of preformed microvascular networks within tissue constructs. In vitro approaches use cell seeding, spheroid formation or cell sheet technologies. In situ approaches use the body as a natural bioreactor to induce vascularization by angiogenic ingrowth or flap and arteriovenous (AV)-loop techniques. In future, these strategies may be supplemented by the transplantation of adipose tissue-derived microvascular fragments or the in vitro generation of highly organized microvascular networks by means of sophisticated microscale technologies and microfluidic systems. The further advancement of these prevascularization concepts and their adaptation to individual therapeutic interventions will markedly contribute to a broad implementation of tissue engineering applications into clinical practice. PMID- 26674313 TI - Endoscopic ultrasonography-guided drainage for patients with symptomatic obstruction and enlargement of the pancreatic duct. AB - AIM: To evaluate the use of translumenal pancreatography with placement of endoscopic ultrasonography (EUS)-guided drainage of the pancreatic duct. METHODS: This study enrolled all consecutive patients between June 2002 and April 2014 who underwent EUS-guided pancreatography and subsequent placement of a drain and had symptomatic retention of fluid in the pancreatic duct after one or more previous unsuccessful attempts at endoscopic retrograde cannulation of the pancreatic duct. In all, 94 patients underwent 111 interventions with one of three different approaches: (1) EUS-endoscopic retrograde drainage with a rendezvous technique; (2) EUS-guided drainage of the pancreatic duct; and (3) EUS-guided, internal, antegrade drainage of the pancreatic duct. RESULTS: The mean duration of the interventions was 21 min (range, 15-69 min). Mean patient age was 54 years (range, 28-87 years); the M:F sex ratio was 60:34. The technical success rate was 100%, achieving puncture of the pancreatic duct including pancreatography in 94/94 patients. In patients requiring drainage, initial placement of a drain was successful in 47/83 patients (56.6%). Of these, 26 patients underwent transgastric/transbulbar positioning of a stent for retrograde drainage; plastic prostheses were used in 11 and metal stents in 12. A ring drain (antegrade internal drainage) was placed in three of these 26 patients because of anastomotic stenosis after a previous surgical intervention. The remaining 21 patients with successful drain placement had transpapillary drains using the rendezvous technique; the majority (n = 19) received plastic prostheses, and only two received metal stents (covered self-expanding metal stents). The median follow-up time in the 21 patients with transpapillary drainage was 28 mo (range, 1-79 mo), while that of the 26 patients with successful transgastric/transduodenal drainage was 9.5 mo (range, 1-82 mo). Clinical success, as indicated by reduced or absence of further pain after the EUS-guided intervention was achieved in 68/83 patients (81.9%), including several who improved without drainage, but with manipulation of the access route. CONCLUSION: EUS-guided drainage of the pancreatic duct is a safe, feasible alternative to endoscopic retrograde drainage when the papilla cannot be reached endoscopically or catheterized. PMID- 26674314 TI - Antifungal prophylaxis: why, what and how? AB - 41st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2015), Istanbul, Turkey, 22-25 March 2015 The European Society for Blood and Marrow Transplantation (EBMT) is the leading scientific society for professionals involved in hematopoietic stem-cell transplantation (HSCT) and represents 563 transplant centers from 57 countries within and outside Europe. Each year, the EBMT Annual Meeting brings together over 4,500 scientists, physicians, nurses, biologists, technicians and patients to discuss scientific data that build on past achievements in the field of HSCT. The procedure offers the chance of long-term remission of hematological and lymphoid cancers, but patients are at increased risk of serious infections, especially after allogeneic HSCT. These infections include the invasive fungal infections that were among the important topics discussed during EBMT 2015. PMID- 26674311 TI - The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate in response to local signaling cues. AB - Vertebrate body axis formation depends on a population of bipotential neuromesodermal cells along the posterior wall of the tailbud that make a germ layer decision after gastrulation to form spinal cord and mesoderm. Despite exhibiting germ layer plasticity, these cells never give rise to midline tissues of the notochord, floor plate and dorsal endoderm, raising the question of whether midline tissues also arise from basal posterior progenitors after gastrulation. We show in zebrafish that local posterior signals specify germ layer fate in two basal tailbud midline progenitor populations. Wnt signaling induces notochord within a population of notochord/floor plate bipotential cells through negative transcriptional regulation of sox2. Notch signaling, required for hypochord induction during gastrulation, continues to act in the tailbud to specify hypochord from a notochord/hypochord bipotential cell population. Our results lend strong support to a continuous allocation model of midline tissue formation in zebrafish, and provide an embryological basis for zebrafish and mouse bifurcated notochord phenotypes as well as the rare human congenital split notochord syndrome. We demonstrate developmental equivalency between the tailbud progenitor cell populations. Midline progenitors can be transfated from notochord to somite fate after gastrulation by ectopic expression of msgn1, a master regulator of paraxial mesoderm fate, or if transplanted into the bipotential progenitors that normally give rise to somites. Our results indicate that the entire non-epidermal posterior body is derived from discrete, basal tailbud cell populations. These cells remain receptive to extracellular cues after gastrulation and continue to make basic germ layer decisions. PMID- 26674316 TI - Cervicovaginal bacterial count and failure of metronidazole therapy for bacterial vaginosis. AB - OBJECTIVE: To evaluate whether total bacterial count in cervicovaginal fluid is associated with failure of metronidazole therapy for bacterial vaginosis. METHODS: In a cross-sectional study, women attending a primary health center in Botucatu, Sao Paulo, Brazil, for routine cervical screening between September 2012 and October 2013 were enrolled. Women who tested positive for bacterial vaginosis (Nugent classification) were offered oral metronidazole. Women who completed metronidazole treatment and an equal number of control women with normal vaginal flora at initial screening were included in analyses of total bacterial count, assessed by flow cytometry of cervicovaginal fluid samples. RESULTS: Of 287 women who enrolled, 49 were excluded because they tested positive for trichomoniasis, chlamydial endocervicitis, gonorrhea, or candidiasis. Among the remaining 238, 85 (35.7%) had bacterial vaginosis. Among 36 women evaluated at follow-up, 23 (63.9%) had successfully restored lactobacilli-dominant flora, 12 (33.3%) had persistent bacterial vaginosis, and 1 (2.8%) had vaginal candidiasis (excluded from flow cytometry). Total bacterial count did not differ between 35 women with bacterial vaginosis and 35 with normal vaginal flora (P=0.62). Total bacterial count did not differ at enrollment between women who went on to have persistent bacterial vaginosis and those who had successful treatment (P=0.78). CONCLUSION: Failure of oral metronidazole therapy for bacterial vaginosis was not associated with total bacterial count in cervicovaginal fluid. PMID- 26674315 TI - Clinical characteristics of early-onset pre-eclampsia in singleton versus multiple pregnancies. AB - OBJECTIVE: To analyze the clinical differences between multiple and singleton pregnancies with early-onset pre-eclampsia. METHODS: The present retrospective cohort study included patients with early-onset pre-eclampsia diagnosed at a tertiary hospital in China between January 2012 and June 2014. The patients were divided into a multiple pregnancy group (MP group) and a singleton pregnancy group (SP group). Differences in maternal and fetal outcomes before and after birth were compared between the two groups. RESULTS: Overall, 100 patients were included (21 MP group; 79 SP group). The systolic and diastolic blood pressure values at admission were significantly lower in the MP group than in the SP group (P=0.032 and P=0.015, respectively), and the incidence of pregnancy edema was significantly higher (P=0.015). Moreover, the mean neonatal birth weight in the MP group was significantly higher than that in the SP group (P<0.001). The frequencies of abnormal umbilical arterial resistance score, abnormal fetal heart rate, low birth weight, low Apgar score, neonatal cardiovascular abnormalities, and neonatal infections were significantly lower in multiple pregnancies (P<0.05 for all). CONCLUSION: Early-onset pre-eclampsia in multiple pregnancies seems to have a protective effect on neonatal survival and improves maternal and fetal outcomes. Disease progression might be delayed when compared with early-onset pre eclampsia in singleton pregnancies. PMID- 26674317 TI - Carcinoembryonic antigen as a biomarker for meconium-stained amniotic fluid. AB - OBJECTIVE: To assess whether elevated carcinoembryonic antigen (CEA) concentration in amniotic fluid can indicate meconium-stained amniotic fluid (MSAF). METHODS: In a prospective cohort study, women with a term singleton pregnancy who were in labor but had intact membranes were recruited at a center in Israel over a 5-month period in 2013. Only women who subsequently underwent artificial rupture of membranes following a clear medical indication were included. Samples of amniotic fluid, urine, and serum were collected. Amniotic fluid was examined by sight and classified as clear, MSAF, or undetermined. CEA concentration in the samples was measured. RESULTS: Among 81 participants, 45 had clear amniotic fluid, 28 had MSAF, and eight had undetermined amniotic fluid. Mean CEA concentration was more than 10 times higher in MSAF (2658 MUg/L, standard error 250) than in clear amniotic fluid (238 MUg/L, standard error 29; P<0.001). Receiver operating characteristic curve analysis demonstrated a sensitivity of 96% and a specificity of 100% for distinguishing MSAF from clear amniotic fluid at a CEA cutoff of 799.2 MUg/L. CEA concentrations in urine and serum were all within the normal range (<=5 MUg/L), irrespective of amniotic fluid status. CONCLUSION: High CEA concentrations in amniotic fluid can assist in the diagnosis of MSAF. These findings could provide the basis for a bedside test to detect MSAF following rupture of membranes. PMID- 26674318 TI - Human parvovirus B19 and low hemoglobin levels in pregnant Sudanese women. AB - OBJECTIVE: To investigate risk factors for, and the seroprevalence of, parvovirus B19 (B19V), as well as the effect of B19V infection on patient hemoglobin levels. METHODS: A cross-sectional study was conducted in Medani Hospital, Sudan between March and July, 2012. Patients with singleton pregnancies were enrolled in the study. Sociodemographic and obstetric characteristics were recorded and enzyme immunoassays were performed to screen for B19V IgG and IgM antibodies. RESULTS: The study enrolled 147 patients. The mean age, parity and duration of pregnancy of the patients were 27.1+/-5.4years, 2.1+/-1.3, and 28.1+/-6.5weeks of pregnancy, respectively. B19V IgG seropositivity was recorded in 73 (49.7%) individuals, with 1 (0.7%) patient seropositive for both B19V IgG and B19V IgM antibodies. Higher parity and residing in rural areas were associated with B19V IgG seropositivity under univariate analyses; however, no sociodemographic or obstetric characteristics were associated with B19V IgG seropositivity when multivariate analyses were performed. Hemoglobin levels were significantly lower in patients who were seropositive for B19V IgG in comparison with patients who were seronegative (99.0+/-10.0g/L vs 104.0+/-10.0g/L; P=0.008). Linear regression demonstrated a significant correlation between B19V IgG seropositivity and hemoglobin level (P=0.008). CONCLUSION: B19V IgG seropositivity was 49.7% among the study group. These patients exhibited lower hemoglobin levels and a significant association was found between B19V IgG seropositivity and hemoglobin level. PMID- 26674319 TI - Characteristics of bacterial acute diarrhea among women. AB - OBJECTIVE: To describe the clinical and microbiological characteristics of women presenting with acute gastroenteritis due to infection with Salmonella spp. or Shigella spp. METHODS: A cross-sectional retrospective study was conducted using data for patients with specimens positive for Shigella spp. and Salmonella spp. attending two major women's hospitals in Porto Alegre, Brazil, between January 2003 and July 2014. Women were included if they had symptoms compatible with bacterial acute diarrhea. Isolates were evaluated to determine antimicrobial susceptibility and patient clinical profile. RESULTS: Among 45 eligible patients, Salmonella spp. was identified in 32 (71%) and Shigella spp. in 13 (29%). The highest antimicrobial sensitivity rates were observed for ciprofloxacin and ceftriaxone (n=44, 98% for both) whereas the greatest resistance rate was seen for ampicillin (n=20, 44%). Seven (16%) of the women were pregnant. CONCLUSION: Ciprofloxacin, ceftriaxone, and sulfamethoxazole/trimethoprim are suitable choices for the treatment of bacterial acute diarrhea. However, the maternal and fetal safety profile of prescribed medications should be considered when treating pregnant patients. PMID- 26674320 TI - A Korean multicenter study of prenatal risk factors for overt diabetes during the postpartum period after gestational diabetes mellitus. AB - OBJECTIVE: To identify prenatal risk factors for postpartum diabetes among pregnant women with gestational diabetes mellitus (GDM). METHODS: In a retrospective study, baseline characteristics and data from a postpartum 75-g glucose tolerance test (GTT) were reviewed for patients with GDM who had delivered in four Korean tertiary institutions from 2006 to 2012. Clinical characteristics were compared between women with and those without postpartum diabetes. Cutoffs to predict postpartum diabetes and diagnostic values were calculated from receiver operating characteristic (ROC) curves. RESULTS: Of 1637 patients with GDM, 498 (30.4%) underwent a postpartum 75-g GTT. Postpartum diabetes was diagnosed in 40 (8.0%) patients and impaired glucose intolerance in 157 (31.5%). Women with postpartum diabetes had higher glycated hemoglobin (HbA1c) levels at GDM diagnosis (P=0.008) and higher 100-g GTT values (P<0.05 for all). In ROC curve analysis, optimal cutoffs for predicting postpartum diabetes were 0.058 for HbA1c level and 5.3 mmol/L (fasting), 10.9 mmol/L (1h), 10.2 mmol/L (2h), and 8.6 mmol/L (3h) for 100-g GTT. The highest sensitivity was observed for 3-h 100-g GTT (76.9%) and the highest positive predictive value was for HbA1c at diagnosis (15.2%). CONCLUSION: HbA1c level at GDM diagnosis and 100 g GTT values could be used to identify patients at high risk of postpartum diabetes who should undergo postpartum screening. PMID- 26674321 TI - Epigenetic regulation of CDH1 exon 8 alternative splicing in gastric cancer. AB - BACKGROUND: The tumor suppressor gene CDH1 is critical for intercellular adhesion. In our previous work, we reported a nonfunctional CDH1 transcript that lacks the final 83 base pairs of exon 8 (1054del83). In this work, we probed the role of histone epigenetic modifications as well as DNA methylation in selection of this isoform. METHODS: RT-qPCR was used to detect CDH1 RNA expression. Methylation of CDH1 was analyzed by bisulphite sequencing PCR. ChIP assay was performed to show histones level. Cell lines were treated with DNA methyltransferase inhibitor AZA, HDAC inhibitor TSA, or siRNA oligonucleotides to test regulation of CDH1 splicing. RESULTS: Greater CDH1 1054del83 transcripts were observed in gastric cancer (GC) cell lines than human gastric mucosal epithelial cell line GES-1. All the cell lines showed significant methylation pattern at the CpG sites of CDH1 exon 8. AZA treatment did not influence selection of 1054del83 transcripts. A significant decrease in acetylation for histones H3 and H4K16Ac in an internal region of the CDH1 gene surrounding the alternative exon 8 were detected in GC cell lines. Treatment with TSA preferentially expressed the correctly spliced transcript and not the exon 8 skipped aberrant transcripts, showing that histone acetylation was involved in the splicing regulation. SiRNA-mediated knockdown of SETD2 (The specific methyltransferase of H3K36) decreased exclusion of exon 8, suggesting that the presence of this mark correlates with increased skipping of the final 83 base pairs of CDH1 exon 8. However, CDH1 splicing was not affected by SRSF2 knockdown. CONCLUSIONS: H3K36me3 correlates with increased skipping of the final 83 base pairs of CDH1 exon 8. Histone acetylation was involved in the splicing regulation as well. PMID- 26674322 TI - Progressive Evaluation of Apoptosis, Proliferation, and Angiogenesis in Fresh Rat Ovarian Autografts Under Remote Ischemic Preconditioning. AB - This study evaluated the remote ischemic preconditioning (R-IPC) early and late repercussion on fresh ovarian transplants, aiming to assess a probable protective effect in ovarian follicular pool. Sixty Wistar EPM-1 rats were used, divided in 2 study groups: ovarian transplantation (Tx) and Tx + R-IPC, submitted to ovary transplant with or without R-IPC, respectively. These groups were subdivided according to the date for euthanasia: 4th, 7th, 14th, 21st, and 30th days of the postoperatory period. Morphology, morphometry, neoangiogenesis (vascular endothelial growth factor [VEGF]), proliferative activity (Ki-67), and apoptosis (cleaved caspase-3) were evaluated. Remote ischemic preconditioning was performed in the common iliac artery. Fresh autologous ovarian tissue was implanted integrally in the retroperitoneum. All animals showed resumption of estrous phase after ovary transplantation. Remote ischemic preconditioning attenuated the lesions progressively from the 7th day, with greater number of the immature follicles (14 days, P < .05), but didn't affect mature follicles and corpora lutea (P > .05). Immunohistochemical analyzes, taken as a whole, show that R-IPC benefic effect is more evident in the later periods of evaluation, when a greater proliferative activity (14, 21, and 30 days, P < .05) and lesser cell apoptotic activity (21 and 30 days, P < .05). The VEGF expression was similar in all times (P > .05). Remote ischemic preconditioning could have a benefic effect in the progressive evaluation of freshly grafted ovarian, especially on the latest phases of the posttransplant period. The 14th day was a landmark in the recuperation of the graft. Further investigations are necessary to determine the role of R-IPC in this scenario and its effect in frozen-thawed ovarian tissue. PMID- 26674323 TI - rhTNFR: Fc Suppresses the Development of Endometriosis in a Mouse Model by Downregulating Cell Proliferation and Invasiveness. AB - Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, may play an important role in the pathogenesis of endometriosis; therefore, TNF-alpha inhibitors potentially have an effect on endometriosis. To investigate the effect of anti-TNF-alpha treatment on endometriosis, 2 TNF-alpha inhibitors: recombinant human TNF receptor: Fc fusion protein (rhTNFR: Fc) and TNF-alpha monoclonal antibody (TNF-alpha mAb) were used to treat human eutopic endometrial stromal cells (hESCs), and the effects on cell survival, cell cycle, and invasiveness were compared. It was found that rhTNFR: Fc suppressed the TNF-alpha-induced hESC survival and invasiveness but not TNF-alpha mAb. Recombinant human TNF receptor: Fc fusion protein decreased the S phase of hESC compared with the TNF-alpha treated group. Then, we used a surgically induced mouse model of endometriosis to study the effect of rhTNFR: Fc treatment in vivo. The fluorescence intensity and the size of implanted endometriotic lesions in the mouse model were decreased by rhTNFR: Fc. In conclusion, rhTNFR: Fc suppresses hESC survival and invasiveness and decreases the fluorescence intensity and implant size in the mouse model of endometriosis. PMID- 26674324 TI - Hydrothermal synthesis and structural characterization of metal-organic frameworks based on new tetradentate ligands. AB - The hydrothermal reaction of two new tetradentate ligands with different metal salts of cadmium nitrate, zinc chloride, cobalt nitrate and deprotonated terephthalic acid (H2tp), isophthalic acid (H2ip), 4,4'-oxybisbenzoic acid (H2obba) in H2O/DMF or H2O/methanol gave three metal-organic frameworks (MOFs): {[Zn2(L1)(tp)(formate)2].H2O}n (), {[Cd2(L2)(ip)2].2H2O}n (), {[Co2(L2)(obba)2]}n () (L1 = 1,2-bis {2,6-bis [(1H-imidazol-1-yl) methyl]-4-methylphenoxy} ethane, L2 = 1,3-bis {2,6-bis [(1H-imidazol-1-yl) methyl]-4-methylphenoxy} propane). The structures of the frameworks are established by single-crystal X-ray diffraction. Compound is a three-dimensional (3D) framework with a 2-fold interpenetrated form, which exhibits a 2-nodal (3,4)-connected fsh-3,4-P21/c net with a {8(3)}2{8(5).10} topology. Compound has a 2-nodal (4,8)-connected 3D framework where the dinuclear cadmium cluster secondary building units (SBUs) assemble with isophthalate and ligand L2 to construct a rare topological type sqc22 net with a {3(2).5(4)}{3(4).4(4).5(10).6(10)} topology. Whereas, Compound can be extended to a 2D interlocked (4,4)-connected 4,4 L28 net with the point symbol {4.6(4).8}2{4(2).6(4)}. L1 and L2 are tetradentate ligands with diverse linkers and display different coordination modes. In addition, the thermal stability and photochemical properties of the frameworks are also investigated. PMID- 26674325 TI - Nonfunctioning giant pituitary adenomas: Invasiveness and recurrence. AB - BACKGROUND: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. METHODS: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. RESULTS: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. CONCLUSION: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence. PMID- 26674326 TI - Bioefficacy of Graviola leaf extracts in scavenging free radicals and upregulating antioxidant genes. AB - The aims of this study were to determine bioactive components of Graviola leaf extracts and to examine the radical scavenging capacity, gene expression and transcription factors of antioxidant enzymes. Rutin, kaempferol-rutinoside, and vitamin U were identified from the steaming and 50% EtOH extracts of Graviola leaves. Graviola leaf extracts effectively scavenged peroxy and nitrogen radicals. 50% EtOH of Graviola leaves provided a 1-2.9 times higher trolox equivalent than the steaming extract. It also had a higher VCEAC. Graviola leaf extracts reduced the generation of reactive oxygen species (ROS) induced by H2O2 in a dose-dependent manner. The 50% EtOH extract of Graviola leaves upregulated SOD1 and Nrf2, but catalase and HMOX1 were not altered by the 50% EtOH extract of Graviola leaves. PMID- 26674328 TI - Odors Help Fruit Flies Escape Parasitoid Wasps. PMID- 26674329 TI - Phosphorylation of GSK3alpha/beta correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients. AB - BACKGROUND: Acute myeloid leukemia (AML) patients with highly active AKT tend to do poorly. Cell cycle arrest and apoptosis are tightly regulated by AKT via phosphorylation of GSK3alpha and beta isoforms which inactivates these kinases. In the current study we examine the prognostic role of AKT mediated GSK3 phosphorylation in AML. METHODS: We analyzed GSK3alpha/beta phosphorylation by reverse phase protein analysis (RPPA) in a cohort of 511 acute myeloid leukemia (AML) patients. Levels of phosphorylated GSK3 were correlated with patient characteristics including survival and with expression of other proteins important in AML cell survival. RESULTS: High levels of p-GSK3alpha/beta correlated with adverse overall survival and a lower incidence of complete remission duration in patients with intermediate cytogenetics, but not in those with unfavorable cytogenetics. Intermediate cytogenetic patients with FLT3 mutation also fared better respectively when p-GSK3alpha/beta levels were lower. Phosphorylated GSK3alpha/beta expression was compared and contrasted with that of 229 related cell cycle arrest and/or apoptosis proteins. Consistent with p GSK3alpha/beta as an indicator of AKT activation, RPPA revealed that p GSK3alpha/beta positively correlated with phosphorylation of AKT, BAD, and P70S6K, and negatively correlated with beta-catenin and FOXO3A. PKCdelta also positively correlated with p-GSK3alpha/beta expression, suggesting crosstalk between the AKT and PKC signaling pathways in AML cells. CONCLUSIONS: These findings suggest that AKT-mediated phosphorylation of GSK3alpha/beta may be beneficial to AML cell survival, and hence detrimental to the overall survival of AML patients. Intrinsically, p-GSK3alpha/beta may serve as an important adverse prognostic factor for a subset of AML patients. PMID- 26674330 TI - Recognizing and preventing epilepsy-related mortality: A call for action. AB - Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half of all epilepsy-related deaths. Some epilepsy groups are especially vulnerable: individuals from low socioeconomic status groups and those with comorbid psychiatric illness die more often than controls. Despite clear evidence of an important public health problem, efforts to assess and prevent epilepsy related deaths remain inadequate. We discuss factors contributing to the underestimation of SUDEP and other epilepsy-related causes of death. We suggest the need for a systematic classification of deaths directly due to epilepsy (e.g., SUDEP, drowning), due to acute symptomatic seizures, and indirectly due to epilepsy (e.g., suicide, chronic effects of antiseizure medications). Accurately estimating the frequency of epilepsy-related mortality is essential to support the development and assessment of preventive interventions. We propose that educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors may reduce epilepsy-related mortality. Educational campaigns regarding sudden infant death syndrome and fires, which kill far fewer Americans than epilepsy, have been widely implemented. We have done too little to prevent epilepsy-related deaths. Everyone with epilepsy and everyone who treats people with epilepsy need to know that controlling seizures will save lives. PMID- 26674331 TI - Oxidative phosphorylation and lacunar stroke: Genome-wide enrichment analysis of common variants. AB - OBJECTIVE: We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA). METHODS: In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes. RESULTS: There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07). CONCLUSIONS: Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes. PMID- 26674332 TI - White and gray matter damage in primary progressive MS: The chicken or the egg? AB - OBJECTIVE: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). METHODS: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. RESULTS: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal appearing WM at 2 years in 3 tracts. CONCLUSION: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID- 26674334 TI - Change in brain network connectivity during PACAP38-induced migraine attacks: A resting-state functional MRI study. AB - OBJECTIVE: To investigate resting-state functional connectivity in the salience network (SN), the sensorimotor network (SMN), and the default mode network (DMN) during migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38 (PACAP38). METHODS: In a double-blind, randomized study, 24 female migraine patients without aura received IV PACAP38 or vasoactive intestinal polypeptide (VIP) over 20 minutes. Both peptides are closely related and cause vasodilation, but only PACAP38 induces migraine attacks. VIP was therefore used as active placebo. Resting-state functional MRI was recorded before and during PACAP38-induced migraine attacks and before and after VIP infusion. We analyzed data by Statistical Parametric Mapping 8 and the Resting-State fMRI Data Analysis Toolkit for Matlab in a seed-based fashion. RESULTS: PACAP38 (n = 16) induced migraine attacks and increased connectivity with the bilateral opercular part of the inferior frontal gyrus in the SN. In SMN, there was increased connectivity with the right premotor cortex and decreased connectivity with the left visual cortex. Several areas showed increased (left primary auditory, secondary somatosensory, premotor, and visual cortices) and decreased (right cerebellum and left frontal lobe) connectivity with DMN. We found no resting-state network changes after VIP (n = 15). CONCLUSIONS: PACAP38-induced migraine attack is associated with altered connectivity of several large-scale functional networks of the brain. PMID- 26674335 TI - Clinician judgment vs formal scales for predicting intracerebral hemorrhage outcomes. AB - OBJECTIVE: To compare the performance of formal prognostic instruments vs subjective clinical judgment with regards to predicting functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This prospective observational study enrolled 121 ICH patients hospitalized at 5 US tertiary care centers. Within 24 hours of each patient's admission to the hospital, one physician and one nurse on each patient's clinical team were each asked to predict the patient's modified Rankin Scale (mRS) score at 3 months and to indicate whether he or she would recommend comfort measures. The admission ICH score and FUNC score, 2 prognostic scales selected for their common use in neurologic practice, were calculated for each patient. Spearman rank correlation coefficients (r) with respect to patients' actual 3-month mRS for the physician and nursing predictions were compared against the same correlation coefficients for the ICH score and FUNC score. RESULTS: The absolute value of the correlation coefficient for physician predictions with respect to actual outcome (0.75) was higher than that of either the ICH score (0.62, p = 0.057) or the FUNC score (0.56, p = 0.01). The nursing predictions of outcome (r = 0.72) also trended towards an accuracy advantage over the ICH score (p = 0.09) and FUNC score (p = 0.03). In an analysis that excluded patients for whom comfort care was recommended, the 65 available attending physician predictions retained greater accuracy (r = 0.73) than either the ICH score (r = 0.50, p = 0.02) or the FUNC score (r = 0.42, p = 0.004). CONCLUSIONS: Early subjective clinical judgment of physicians correlates more closely with 3-month outcome after ICH than prognostic scales. PMID- 26674337 TI - Biology Open: evaluating impact. PMID- 26674336 TI - Gastric Cancer: New Drugs - New Strategies. AB - BACKGROUND: Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed. SUMMARY: The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. KEY MESSAGE: The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways. PRACTICAL IMPLICATIONS: Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under development. PMID- 26674338 TI - Physical Modeling of Gate-Controlled Schottky Barrier Lowering of Metal-Graphene Contacts in Top-Gated Graphene Field-Effect Transistors. AB - A new physical model of the gate controlled Schottky barrier height (SBH) lowering in top-gated graphene field-effect transistors (GFETs) under saturation bias condition is proposed based on the energy conservation equation with the balance assumption. The theoretical prediction of the SBH lowering agrees well with the experimental data reported in literatures. The reduction of the SBH increases with the increasing of gate voltage and relative dielectric constant of the gate oxide, while it decreases with the increasing of oxide thickness, channel length and acceptor density. The magnitude of the reduction is slightly enhanced under high drain voltage. Moreover, it is found that the gate oxide materials with large relative dielectric constant (>20) have a significant effect on the gate controlled SBH lowering, implying that the energy relaxation of channel electrons should be taken into account for modeling SBH in GFETs. PMID- 26674333 TI - Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke. AB - OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 * 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 * 10(-8); rs941898 [EVL], p = 4.0 * 10(-8); rs962888 [C1QL1], p = 1.1 * 10(-8); rs9515201 [COL4A2], p = 6.9 * 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. PMID- 26674339 TI - Injury Risk in International Rugby Union: Three-Year Injury Surveillance of the Welsh National Team. AB - BACKGROUND: Within international Rugby Union, only injury rates during the Rugby World Cup have been reported. Therefore, injury rates and types during other international tournaments are unknown. PURPOSE: To assess the 3-year incidence, severity, nature, and causes of match and training injuries sustained during different international tournaments played by the Welsh national Rugby Union team. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury data for all players (n = 78) selected for 1 national Rugby Union team over a 3-year period were analyzed using the international consensus statement methods. Player height (cm) and mass (kg) were recorded. Tournaments were grouped for comparisons as: autumn tournaments (2012 and 2013), Rugby World Cup (RWC; 2011), Six Nations (2012, 2013, and 2014), and summer tournaments (2012, 2013, and 2014). Injury incidence (injuries/1000 hours), prevalence (% of players unavailable), and severity (days lost) were calculated for each tournament. Injury location, type, and cause of match and training injuries were analyzed. RESULTS: Match injury incidence was highest during autumn tournaments (262.5/1000 match-hours) and lowest during the RWC (178.6/1000 match-hours). Summer tournaments had the highest training incidence (5.5 injuries/1000 training-hours). Mild injuries were most likely during the RWC (risk ratio [RR], 2.02; 95% CI, 1.26-3.24), while severe injuries were most likely during autumn tournaments (RR, 3.27; 95% CI, 1.70-6.29). Quadriceps hematomas (18.8/1000 match-hours; 95% CI, 11.3-31.1) and concussions (13.8/1000 match-hours; 95% CI, 7.6-24.8) were the most common match injuries, with shoulder dislocations being the most severe (111 mean days lost per injury). CONCLUSION: Injury rates were considerably higher than those previously reported for multiple teams during RWC tournaments. Further investigation of injury rates and risk factors is recommended to accurately gauge their impact within international Rugby Union, particularly with regard to lower limb hematoma, concussion, and shoulder injuries. PMID- 26674340 TI - The Association of Low-To-Moderate Alcohol Consumption with Breast Cancer Subtypes Defined by Hormone Receptor Status. AB - BACKGROUND: Alcohol is a well-established risk factor for breast cancer, but pathways involved in alcohol-related breast carcinogenesis are not clearly defined. We examined the association between low-to-moderate alcohol intake and breast cancer subtypes by tumor hormone receptor status. MATERIALS AND METHODS: A hospital-based case-control study was performed in 585 cases and 1,170 controls. Information on alcohol intake and other risk factors was collected via a questionnaire. Logistic regression was used for analyses. All statistical tests were two-sided. RESULTS: The odds ratio of breast cancer was 1.75 (95% confidence interval [CI]: 1.21-2.53) in women who consumed <=5 drinks/week, and 3.13 (95% CI: 1.81-5.43) in women who consumed >5 drinks/week, both compared with non drinkers for >=10 years, after adjustment for age and other confounders. The association of alcohol intake with estrogen receptor-positive breast cancer was stronger than with estrogen receptor-negative: the odds ratio per 1 category increase was 2.05 (95% CI: 1.49-2.82) and 1.29 (95% CI: 0.85-1.94) (P heterogeneity = 0.07). There was no evidence of an interaction between alcohol intake and menopausal status (P = 0.19) in overall group; however, it was significant in estrogen receptor-positive breast cancer (P = 0.04). CONCLUSIONS: Low-to-moderate alcohol intake is associated with the risk of estrogen receptor positive breast cancer with the strongest association in postmenopausal women. Since alcohol intake is a modifiable risk factor of breast cancer, every woman should be informed and advised to control alcohol use. PMID- 26674341 TI - Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells. AB - Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/beta-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/beta-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering. [BMB Reports 2016; 49(3): 179-184]. PMID- 26674342 TI - A systematic study of nuclear interactome of C-terminal domain small phosphatase like 2 using inducible expression system and shotgun proteomics. AB - RNA polymerase II C-terminal domain phosphatases are newly emerging family of phosphatases that contain FCPH domain with Mg+2-binding DXDX(T/V) signature motif. Its subfamily includes small CTD phosphatases (SCPs). Recently, we identified several interacting partners of human SCP1 with appearance of dephosphorylation and O-GlcNAcylation. In this study, using an established cell line with inducible CTDSPL2 protein (a member of the new phosphatase family), proteomic screening was conducted to identify binding partners of CTDSPL2 in nuclear extract through immunoprecipitation of CTDSPL2 with its associated. This approach led to the identification of several interacting partners of CTDSPL2. This will provide a better understanding on CTDSPL2. [BMB Reports 2016; 49(6): 319-324]. PMID- 26674343 TI - Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif. AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a homo trimeric cytotoxic ligand. Several studies have demonstrated that incorporation of artificial trimerization motifs into the TRAIL protein leads to the enhancement of biological activity. Here, we show that linkage of the isoleucine zipper hexamerization motif to the N-terminus of TRAIL, referred as ILz(6):TRAIL, leads to multimerization of its trimeric form, which has higher cytotoxic activity compared to its native state. Size exclusion chromatography of ILz(6):TRAIL revealed possible existence of various forms such as trimeric, hexameric, and multimeric (possibly containing one-, two-, and multi-units of trimeric TRAIL, respectively). Increased number of multimerized ILz(6):TRAIL units corresponded with enhanced cytotoxic activity. Further, a high degree of ILz(6):TRAIL multimerization triggered rapid signaling events such as activation of caspases, tBid generation, and chromatin condensation. Taken together, these results indicate that multimerization of TRAIL significantly enhances its cytotoxic activity. [BMB Reports 2016; 49(5): 282-287]. PMID- 26674344 TI - Dopamine-dependent synaptic plasticity in an amygdala inhibitory circuit controls fear memory expression. AB - Of the numerous events that occur in daily life, we readily remember salient information, but do not retain most less-salient events for a prolonged period. Although some of the episodes contain putatively emotional aspects, the information with lower saliency is rarely stored in neural circuits via an unknown mechanism. We provided substantial evidence indicating that synaptic plasticity in the dorsal ITC of amygdala allows for selective storage of salient emotional experiences, while it deters less-salient experience from entering long term memory. After activation of D4R or weak fear conditioning, STDP stimulation induces LTD in the LA-ITC synapses. This form of LTD is dependent upon presynaptic D4R, and is likely to result from enhancement of GABA release. Both optogenetic abrogation of LTD and ablation of D4R at the dorsal ITC in vivo lead to heightened and over-generalized fear responses. Finally, we demonstrated that LTD was impaired at the dorsal ITC of PTSD model mice, which suggests that maladaptation of GABAergic signaling and the resultant LTD impairment contribute to the endophenotypes of PTSD. PMID- 26674345 TI - Investigation of the Possibility of Using Serum Ischemia Modified Albumin (IMA) as a Novel and Early Marker of the Extent of Oxidative Stress Induced by Various Tobacco Products. AB - BACKGROUND: Ischemia Modified Albumin (IMA) is an altered serum albumin that forms under the conditions of oxidative stress and is considered as a biomarker of cardiac ischemia. The objective of this study was to evaluate the ischemia modified albumin (IMA) in the serum of the individuals with different types of tobacco habits in order to investigate the possibility of using this as a biomarker for the oxidative stress induced by the tobacco products. MATERIALS AND METHODS: The study included 90 subjects, who were Grouped as control (30), Group I (betel quid chewers), Group II (gutkha chewers), Group III (smokers) and Group IV (mixed). Serum was collected from subjects of all Groups and IMA estimation was done using Albumin Cobalt binding assay. The results were tabulated and analysed statistically. RESULTS: The mean serum IMA levels in control, Group I, Group II, Group III and Group IV were 0.52547 ABSU, 0.68767 ABSU, 0.47433 ABSU,0.36540 ABSU and 0.54593 ABSU respectively. CONCLUSION: The results show that serum IMA levels were increased in betel quid chewers and mixed Group compared to the controls. From the results noted in this study we suggest that IMA can be used as an early marker for tobacco related oxidative stress. PMID- 26674346 TI - Resin from Virola oleifera Protects Against Radiocontrast-Induced Nephropathy in Mice. AB - Contrast-induced nephropathy (CIN) is an iatrogenic medical event for which there is not yet a successful therapy. Increasing evidence in rodents has suggested that this disease is associated with renal tubular and vascular injury that is triggered directly by oxidative stress. In the present study, we evaluated whether the antioxidant resin from Virola oleifera (RV) could attenuate renal damage in an experimental mouse model of CIN. Adult male Swiss mice were divided into six groups and pre-treated orally with RV (10, 100 and 300 mg/kg), N acetylcysteine (200 mg/kg) or vehicle for 5 days before the induction of CIN and Control group. Renal function was assessed by measuring plasma creatinine and urea levels. Additionally, renal oxidative stress and apoptosis/cell viability were determined with flow cytometry. Finally, kidney tissues were sectioned for histopathological examination. In this CIN model, pre-treatment with RV improved renal function, lowered the mortality rate, and reduced oxidative stress and apoptosis in both the medulla and cortex renal cells in a dose-dependent manner. Moreover, the RV treatment had beneficial effects on kidney histopathology that were superior to the standard treatment with N-acetylcysteine. These data suggest that because of its antioxidative and antiapoptotic effects and its ability to preserve renal function, resin from Virola oleifera may have potential as a new therapeutic approach for preventing CIN. PMID- 26674347 TI - The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations. AB - Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient. PMID- 26674348 TI - An Active 32-kDa Cathepsin L Is Secreted Directly from HT 1080 Fibrosarcoma Cells and Not via Lysosomal Exocytosis. AB - Cathepsin L [EC 3.4.22.15] is secreted via lysosomal exocytosis by several types of cancer cells, including prostate and breast cancer cells. We previously reported that human cultured fibrosarcoma (HT 1080) cells secrete cathepsin L into the medium; this secreted cathepsin is 10-times more active than intracellular cathepsin. This increased activity was attributed to the presence of a 32-kDa cathepsin L in the medium. The aim of this study was to examine how this active 32-kDa cathepsin L is secreted into the medium. To this end, we compared the secreted active 32-kDa cathepsin L with lysosomal cathepsin L by using a novel gelatin zymography technique that employs leupeptin. We also examined the glycosylation and phosphorylation status of the proteins by using the enzymes endoglycosidase H [EC 3.2.1.96] and alkaline phosphatase [EC 3.1.3.1]. Strong active bands corresponding to the 32-kDa and 34-kDa cathepsin L forms were detected in the medium and lysosomes, respectively. The cell extract exhibited strong active bands for both forms. Moreover, both forms were adsorbed onto a concanavalin A-agarose column. The core protein domain of both forms had the same molecular mass of 30 kDa. The 32-kDa cathepsin L was phosphorylated, while the 34-kDa lysosomal form was dephosphorylated, perhaps because of the lysosomal marker enzyme, acid phosphatase. These results suggest that the active 32-kDa form does not enter the lysosomes. In conclusion, our results indicate that the active 32-kDa cathepsin L is secreted directly from the HT 1080 cells and not via lysosomal exocytosis. PMID- 26674349 TI - Prolapse of fallopian tube through abdominal wound after caesarean section mimicking scar endometriosis: a case report. AB - INTRODUCTION: Prolapse of the fallopian tube after hysterectomy is a rare but known complication. Cases of prolapse of the fallopian tube through the vaginal vault have been reported after abdominal, vaginal or laparoscopic hysterectomies. This is the first case report to the best of our knowledge on the prolapse of a fallopian tube through an abdominal wound after caesarean section. CASE PRESENTATION: We report a case of the prolapse of the fimbrial end of a fallopian tube through an abdominal scar after caesarean section mimicking scar endometriosis. A 24-year-old primipara South Asian woman of Punjabi ethnicity presented to our institute with a fleshy mass protruding through her abdominal scar and bleeding from the mass during menstruation for the past 5 months. She underwent a caesarean section 6 months earlier for breech presentation. Her history revealed she had wound dehiscence on the sixth postoperative day. The major portion of her wound healed in 1 month leaving a 2 cm area in the middle of her vertical scar. An abdominal examination revealed a 2*2 cm fleshy mass protruding through the middle part of her infraumbilical abdominal scar. At the time of the surgery we found that the fimbrial end of her left fallopian tube was protruding through her abdominal scar. CONCLUSION: Awareness of this complication may prevent improper management of wound dehiscence and such complication causing prolonged agony to the patient. PMID- 26674350 TI - Brevundimonas albigilva sp. nov., isolated from forest soil. AB - Strain NHI-13T, a Gram-stain-negative, aerobic and short rod-shaped bacterium, was isolated from forest soil at Kyonggi University in Suwon, South Korea. It grew optimally in R2A medium, at 20-30 degrees C, in the presence of 0-4 % NaCl. Colonies resulting from incubation of the strain on agar plates for 2 days were circular, raised, translucent, viscous and whitish-yellow, with entire margins. This strain exhibited high catalase activity but was negative for oxidase. 16S rRNA gene sequence analysis showed that strain NHI-13T formed a coherent cluster with members of the genus Brevundimonas. Its similarities were 98.0 % with Brevundimonas aurantiaca DSM 4731T, 97.9 % with Brevundimonas vesicularis LMG 2350T, 97.6 % with Brevundimonas intermedia ATCC 15262T, 97.5 % with Brevundimonas nasdae GTC 1043T, 97.1 % with 'Brevundimonas olei' MJ15, 97.1 % with Brevundimonas mediterranea V4.BO.10T and 97.0 % with Brevundimonas poindexterae FWC40T. The major cellular fatty acids were summed feature 8 (C18 : 1omega7c/C18 : 1omega6c), C16 : 0 and 11-methyl C18 : 1omega7c. The DNA G+C content was 63 mol%. The predominant quinone was ubiquinone Q-10. The polar lipid profile contained 1,2-di-O-acyl-3-O-alpha-d-glycopyranuronosyl glycerol, 1,2-di-O acyl-3-O-alpha-d-glycopyranosyl glycerol, 1,2-di-O-acyl-3-O-[d-glycopyranosyl (1 > 4)-alpha-d-glucopyranuronosyl] glycerols, phosphatidylglycerol, 1,2-diacyl-3- O (6'-phosphatidyl-alpha-d-glucopyranosyl) glycerol and other unknown lipids. The DNA relatedness of strain NHI-13T with its reference strains was in the range of 43-56 %. On the basis of its phenotypic, genotypic, chemotaxonomic and phylogenetic distinctiveness, strain NHI-13T is suggested to be a representative of a novel species, belonging to the genus Brevundimonas. Therefore, the name Brevundimonas albigilva. sp. nov. is proposed, with the type strain being NHI-13T ( = KEME 9005-016T = KACC 18249T = JCM 30385T). PMID- 26674351 TI - Logic regression-derived algorithms for syndromic management of vaginal infections. AB - BACKGROUND: Syndromic management of vaginal infections is known to have poor diagnostic accuracy. Logic regression is a machine-learning procedure which allows for the identification of combinations of variables to predict an outcome, such as the presence of a vaginal infection. METHODS: We used logic regression to develop predictive models for syndromic management of vaginal infection among symptomatic, reproductive-age women in south India. We assessed the positive predictive values, negative predictive values, sensitivities and specificities of the logic regression procedure and a standard WHO algorithm against laboratory confirmed diagnoses of two conditions: metronidazole-sensitive vaginitis [bacterial vaginosis or trichomoniasis (BV/TV)], and vulvovaginal candidiasis (VVC). RESULTS: The logic regression procedure created algorithms which had a mean positive predictive value of 61 % and negative predictive value of 80 % for management of BV/TV, and a mean positive predictive value of 26 % and negative predictive value of 98 % for management of VVC. The results using the WHO algorithm were similarly mixed. CONCLUSIONS: The logic regression procedure identified the most predictive measures for management of vaginal infections from the candidate clinical and laboratory measures. However, the procedure provided further evidence as to the limits of syndromic management for vaginal infections using currently available clinical measures. PMID- 26674352 TI - Perioperative Safety of Warfarin Therapy and Reversal. AB - BACKGROUND: Warfarin is the most widely prescribed oral anticoagulant frequently encountered in the patients presenting for both elective and emergent surgery. Maintaining therapeutic levels of warfarin therapy may increase the risk of blood loss and procedural complications, including complications from neuraxial and regional anesthetic techniques. However, in some vulnerable patient groups, discontinuing therapy may result in negative thromboembolic consequences. OBJECTIVE: To review the published guidelines and supporting data from clinical studies addressing the safe and coordinated management of patients on warfarin therapy who present for perioperative care. METHOD: This review highlights the most up-to-date research from clinical trials as well as from retrospective studies in addition to multidisciplinary consensus guidelines regarding the safety of warfarin therapy and reversal in the perioperative period. RESULTS: Based on the most up-to-date literature, certain patient groups may be more vulnerable to cessation of warfarin therapy before surgery and there exists a risk stratification algorithm. In many other cases, particularly emergent surgery, it may be necessary to reverse warfarin therapy preoperatively. There are anesthetic, surgical and safety implications in these clinical decision points. CONCLUSION: With the aging of the United States population, the prevalence of preoperative patients therapeutic on warfarin will continue to increase, necessitating the multidisciplinary and coordinated care of perioperative clinicians to ensure patient safety and optimize clinical outcomes. PMID- 26674353 TI - Comparison of the Roche cobas(r) 4800 and Digene Hybrid Capture(r) 2 HPV tests for primary cervical cancer screening in the HPV FOCAL trial. AB - BACKGROUND: HPV FOCAL is a randomized trial (ISRCTN79347302, registered 20 Apr 2007) comparing high-risk (hr) HPV testing vs. liquid-based cytology (LBC) for cervical cancer screening of women aged 25-65. We compared the Digene Hybrid Capture(r) 2 High-Risk HPV DNA Test(r) (HC2) and the Roche cobas(r) 4800 HPV Test (COBAS) for primary screening. METHODS: Women (n=6,172) were screened at baseline by HC2 and COBAS and by LBC 24 months later. We assessed HPV genotyping and reflex LBC for colposcopy triage of baseline HPV positive women. RESULTS: Overall HC2/COBAS agreement was 96.1% (kappa 0.75) and positive agreement was 77.5%. Baseline CIN2 and CIN3+ rates based on HPV screening were 8.6/1,000 and 6.6/1,000 respectively; 24 month rates were 0.7/1,000 and 0.4/1,000 (LBC screening). HC2 and COBAS were concordant positive for 91% of round 1 CIN2 and 98% of CIN3+. CIN3+ was significantly associated with HPV 16 (Odds Ratio [OR] 5.11; 95% confidence interval [CI] 2.30, 11.37), but not HPV 18 (OR 2.62; 95% CI 0.73, 9.49), vs. non-HPV 16/18 HPV at baseline. There was no significant association between HPV genotype and CIN2. CIN3+ was significantly more likely for high-grade (OR 5.99; 95% CI 2.53, 14.18), but not low-grade (OR 0.54; 95% CI 0.20, 1.49), vs. negative LBC. No significant association was observed between LBC grade and CIN2. HPV 16 and 18 were associated with 33% of CIN2 and 68% of CIN3+ identified at baseline. CONCLUSIONS: For hrHPV positive women, abnormal reflex LBC is appropriate for colposcopy triage. In addition, immediate referral of women with HPV 16/18 and normal cytology may allow for earlier detection of CIN2+ lesions which would not be detected until after follow-up testing. PMID- 26674354 TI - Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases. AB - BACKGROUND: In asthma and chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion contributes to impaired mucociliary clearance, mucostasis and, potentially, the development of mucus plugging of the airways. SUMMARY: Excess mucus production can be targeted via therapies that focus on inhibition mucin synthesis, via reducing expression of mucin (MUC) genes, and/or inhibition of mucin secretion into the airways. KEY MESSAGES: This review discusses a number of therapeutic approaches to reduce airway mucus in asthma and COPD, including the use of synthetic and natural products. In particular, it highlights areas where clinical trials of inhibitors of particular target molecules are lacking. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are an example of a targeted therapy that has been researched to reduce mucus synthesis, as have inhibitors of EGFR's downstream signalling pathways, for example, mitogen activated protein kinase-13 and hypoxia inducible factor-1. However, their efficacy and safety profiles are currently not up to the mark. There is clinical potential in Bio-11006, which reduces mucus secretion via the inhibition of myristoylated alanine-rich C-kinase substrate and is currently in Phase IIb trial. PMID- 26674355 TI - The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3beta Inactivation. AB - Glycogen synthase kinase-3beta (GSK-3beta) acts as a negative regulator of NF-E2 related factor 2 (Nrf2) by inducing Nrf2 degradation and nuclear export. Our previous study demonstrated that the flavonoid hyperoside elicits cytoprotection against oxidative stress by activating the Keap1-Nrf2-ARE signaling pathway, thus increasing the expression of antioxidant enzymes, such as heme oxygenase-1 (HO 1), superoxide dismutase (SOD) and catalase. However, the role of GSK-3beta in hyperoside-mediated Nrf2 activation is unclear. Here, we demonstrate that in a normal human hepatocyte cell line, (L02), hyperoside is capable of inducing the phosphorylation of GSK-3beta at Ser9 without affecting the protein levels of GSK 3beta and its phosphorylation at Thr390. Lithium chloride (LiCl) and short interfering RNA (siRNA)-mediated inhibition of GSK-3beta significantly enhanced the ability of hyperoside to protect L02 liver cells from H2O2-induced oxidative damage, leading to increased cell survival shown by the maintenance of cell membrane integrity and elevated levels of glutathione (GSH), one of the endogenous antioxidant biomarkers. Further study showed that LiCl and siRNA mediated inhibition of GSK-3beta increased hyperoside-induced HO-1 expression, and the effect was dependent upon enhanced Nrf2 nuclear translocation and gene expression. These activities were followed by ARE-mediated transcriptional activation in the presence of hyperoside, which was abolished by the transfection of the cells with Nrf2 siRNA. Furthermore, the siRNA-mediated inhibition of Keap1 also enhanced hyperoside-induced Nrf2 nuclear accumulation and HO-1 expression, which was relatively smaller than the effects obtained from GSK-3beta siRNA administration. Moreover, Keap1 siRNA administration alone had no significant effect on the phosphorylation and protein expression of GSK-3beta. Collectively, our data provide evidence that hyperoside attenuates H2O2 -induced L02 cell damage by activating the Nrf2-ARE signaling pathway through both an increase in GSK-3beta inhibitory phosphorylation at Ser9 and an inhibition of Keap1 and that hyperoside-mediated GSK-3beta inhibition exhibits more significant effects. PMID- 26674356 TI - Sonographic assessment of the inferior vena cava/aorta index measured with the transducer placed in the anterior median line and right anterior axillary line - a comparison. AB - The aim of the study was to compare the values of the sonographic inferior vena cava/ aorta index obtained with the transducer placed in the median line and right anterior axillary line. MATERIAL AND METHODS: The study enrolled 45 volunteers, including 33 women, aged 22.5 +/- 1.26 with a negative history of circulatory and renal diseases. The study consisted in a sonographic assessment and measurement of the inferior vena cava and aorta by placing the transducer in the anterior median line and right anterior axillary line. The value of the inferior vena cava/aorta index was obtained by calculating the ratio of the diameters of the inferior vena cava and aorta. The diameter measurements were taken by placing the ultrasound transducer in the anterior median line and right anterior axillary line. Two examiners performed the measurement three times and used convex probes of 3.5-5 MHz. Additionally, the subjects' weight, height and arterial blood pressure were taken. RESULTS: Following a statistical analysis with the use of STATISTICA software, the following values of the inferior vena cava/aorta index were obtained: in the anterior median line - 1.43 +/- 0.21, and in the right anterior axillary line - 1.285 +/- 0.19. There was no statistically significant difference between the measurements obtained by the two examiners (p = 0.17). A strong correlation was noted between the inferior vena cava/ aorta indices calculated in both sites of transducer placement, which was irrespective of the examiners (the correlation coefficient: r = 0.61 and r = 0.71). The study indicate that the inferior vena cava/aorta index measured in the right anterior axillary line is a simple and reproducible method for determining the body fluid status; the examinations conducted in both sites may be used interchangeably. Further studies are needed to determine reference values for the inferior vena cava/aorta index measured in the right anterior axillary line. PMID- 26674357 TI - A Mathematical Model of Intra-Colony Spread of American Foulbrood in European Honeybees (Apis mellifera L.). AB - American foulbrood (AFB) is one of the severe infectious diseases of European honeybees (Apis mellifera L.) and other Apis species. This disease is caused by a gram-positive, spore-forming bacterium Paenibacillus larvae. In this paper, a compartmental (SI framework) model is constructed to represent the spread of AFB within a colony. The model is analyzed to determine the long-term fate of the colony once exposed to AFB spores. It was found out that without effective and efficient treatment, AFB infection eventually leads to colony collapse. Furthermore, infection thresholds were predicted based on the stability of the equilibrium states. The number of infected cell combs is one of the factors that drive disease spread. Our results can be used to forecast the transmission timeline of AFB infection and to evaluate the control strategies for minimizing a possible epidemic. PMID- 26674358 TI - Histological Spectrum of Large Intestinal Lesions with Clinicopathological Correlation. AB - INTRODUCTION: Large intestine is affected by various types of lesions, both non neoplastic and neoplastic. Due to vague symptoms, the clinical diagnosis is usually delayed. A battery of laboratory tests including biopsy is essential to arrive at a specific diagnosis for appropriate management. MATERIALS AND METHODS: This five years study was done during the period of 2005 to 2010 in a tertiary care centre which included 124 biopsies and resected specimens of large intestine and 64 from Anal canal. All tissues were fixed in formalin, stained with H&E and special stains like Periodic Acid Schiff (PAS), Reticulin, Zeihl Neelsen (ZN) along with Immunohistochemistry (IHC) were done as and when required. RESULTS: Out of the 124 cases of large intestine 38 were non-neoplastic, 77 were neoplastic and 9 were inadequate biopsies. Sixty four cases from Anal canal included 55 non-neoplastic and 9 neoplastic lesions. The non-neoplastic conditions included congenital anomalies, infective and ischaemic lesions while neoplastic included benign and malignant lesions. Most of the cases presented with symptoms like abdominal pain, vomiting and constipation. CONCLUSION: We observed that neoplastic lesions were more common in large intestine while non neoplastic lesions were frequently seen in Anal canal. Present study emphasizes the need for early histopathological diagnosis for appropriate treatment. PMID- 26674359 TI - Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection. AB - OBJECTIVE: Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection. DESIGN: NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV infected individuals by flow cytometry and ELISA, respectively. NK cell degranulation and cytokine secretion were determined by flow cytometry. 65 patients with chronic HBV infection, 84 with chronic biliary disorders and 168 healthy donors served as controls. RESULTS: Expression of Siglec-7 was significantly decreased on NK cells from HCV-infected and HBV-infected patients and, conversely, serum Siglec-7 was significantly increased in these patients compared with controls. The frequency of Siglec-7pos NK cells was significantly higher at baseline in sustained virological responders to pegylated interferon alpha/ribavirin treatment than in non-responders. Activating receptor expression was significantly higher in Siglec-7pos NK cells and was associated with increased degranulation and cytokine secretion compared with Siglec-7neg cells. In chronic HCV infection, there was an inverse correlation between Siglec-7 expression and serum aminotransferases, gamma-glutamyl transpeptidase, liver stiffness, aspartate aminotransferase to platelet ratio index and fibrosis-4 scores, and a positive correlation between serum Siglec-7 and the same clinical parameters, including histological staging. CONCLUSIONS: These findings identify Siglec-7neg NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection. PMID- 26674360 TI - Adenoma detection with Endocuff colonoscopy versus conventional colonoscopy: a multicentre randomised controlled trial. AB - BACKGROUND AND AIMS: Colonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC). METHODS: We performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as well as symptomatic patients (>45 years). Consenting patients were randomised 1:1 to EAC or CC. All colonoscopies were performed by experienced colonoscopists (>=500 colonoscopies) who were trained in EAC. All colonoscopy quality indicators were prospectively recorded. FINDINGS: Of the 1063 included patients (52% male, median age 65 years), 530 were allocated to EAC and 533 to CC. More adenomas were detected with EAC, 722 vs 621, but the gain in MAP was not significant: on average 1.36 per patient in the EAC group versus 1.17 in the CC group (p=0.08). In a per-protocol analysis, the gain was 1.44 vs 1.19 (p=0.02), respectively. In the EAC group, 275 patients (52%) had one or more adenomas detected versus 278 in the CC group (52%; p=0.92). For advanced adenomas these numbers were 109 (21%) vs 117 (22%). The adjusted caecal intubation rate was lower with EAC (94% vs 99%; p<0.001), however when allowing crossover from EAC to CC, they were similar in both groups (98% vs 99%; p value=0.25). INTERPRETATION: Though more adenomas are detected with EAC, the routine use of Endocuff does not translate in a higher number of patients with one or more adenomas detected. Whether increased detection ultimately results in a lower rate of interval carcinomas is not yet known. TRIAL REGISTRATION NUMBER: http://www.trialregister.nl Dutch Trial Register: NTR3962. PMID- 26674361 TI - Frequency of Sperm DNA Fragmentation According to Selection Method: Comparison and Relevance of a Microfluidic Device and a Swim-up Procedure. AB - INTRODUCTION: Multiple rounds of centrifugation or washing spermatozoa can cause sperm DNA fragmentation (SDF); however, a microfluidic approach to select spermatozoa does not require centrifugation. Reports have suggested that sperm sorting using a microfluidic device is an effective method to select good quality spermatozoa, however, it is not known whether it reduces sperm DNA damage. We investigated whether the frequency of SDF was affected by selection method during sperm processing. MATERIALS AND METHODS: Semen samples from ten men with normal, oligozoospermia and asthenozoospermia were split into two groups and sorted using a microfluidic device or by a swim-up method. Subsequently, semen parameters and SDF were measured and analyzed using paired or non-paired Student's t-tests. RESULTS: For samples sorted by the microfluidic device (Sperm Sorter Qualis((r)); Menicon, Kasugai, Japan) or the swim-up method, both showed a decrease in SDF. However, the decrease was more significant when the microfluidic device was used. CONCLUSION: Sorting using the microfluidic device resulted in less SDF than did the swim-up method. PMID- 26674362 TI - Levels of depressive symptoms may modify the relationship between the WHOQOL-BREF and its determining factors in community-dwelling older adults. AB - BACKGROUND: Depression is closely associated with quality of life (QOL) in older adults. Being elderly and exhibiting mild depressive symptoms may not lead to a depression diagnosis, but these attributes are clinically important. However, the extent to which these factors influence QOL and its determinants in older adults remains unclear. METHODS: Questionnaires were administered to people aged 65 years or older at community senior centers in Taiwan to collect socio-demographic information and to assess results from the brief version of the World Health Organization's Quality of Life instrument (WHOQOL-BREF), Modified Barthel Index (MBI), 15-item Geriatric Depression Scale (GDS), and Mini-Mental State Examination (MMSE). Levels of depressive symptoms were classified as no depressive symptoms (NDS), lower level of depressive symptoms (LLDS), and higher level of depressive symptoms (HLDS), corresponding to GDS = 0, 1?GDS?5, and GDS>5, respectively. Multiple linear regression analyses were conducted to assess associations between the WHOQOL-BREF and its covariates for different levels of depressive symptoms. RESULTS: A total of 454 older adults participated. The GDS and MBI scores significantly affected the WHOQOL-BREF physical and psychological domain scores in the LLDS group. Gender influenced the WHOQOL-BREF scores in the NDS group, and increased age demonstrated protective effects on the three domains in the HLDS group. Moreover, the association between the WHOQOL-BREF and its covariates varied for different levels of depressive symptoms. CONCLUSIONS: Treatment for depressive symptoms is of high priority, and early recognition of and appropriate intervention for mild depressive symptoms may improve community dwelling older adults' QOLs. PMID- 26674363 TI - Common Presentation with Uncommon Diagnosis: Multifocal Epithelioid Hemangioendothelioma. AB - A young female patient presenting with recurrent hemoptysis, neck swelling, and mediastinal mass mimicking lymphadenopathy was admitted to the Institute of Post Graduate Medical Education and Research and SSKM hospital, Kolkata, India. Clinical features, radiological studies, fibre optic bronchoscopy, and fine needle aspiration cytology from the neck swelling created a diagnostic dilemma until surgical resection and immunohistochemistry reports confirmed the diagnosis of multifocal epithelioid hemangioendothelioma, a rare vascular tumor with intermediate malignancy potential. Because it is a slow-progressing disease and due to the non-availability of standard chemotherapy, the patient, and her legal guardian, opted for palliative care only. She was asymptomatic for four years but again presented with hemoptysis, reappearance of the neck swelling on the same side, and a mediastinal mass compressing the superior vena cava and right pulmonary artery. This report describes the diagnostic problems and therapeutic challenges in the management of this rare tumor over a four-year follow-up period. The clinical course emphasizes the highly unpredictable nature of this tumor. PMID- 26674364 TI - Enhancing the Scratch Resistance by Introducing Chemical Bonding in Highly Stretchable and Transparent Electrodes. AB - Stretchable transparent electrodes are key elements in flexible electronics and e skins. However, existing stretchable transparent electrodes, including graphene sheets, carbon nanotube, and metal nanowire networks, weakly adheres to the substrate by van der Waals forces. Such electrodes suffer from poor scratch resistance or poor durability, and this issue has been one of the biggest problems for their applications in industry. Here we show that, by introducing a Au-S bond between a Au nanomesh (AuNM) and the underlying elastomeric substrate, the AuNM strongly adheres to the substrate and can withstand scratches of a pressure of several megapascals. We find that the strong chemical bond, on the other hand, leads to a stiffening effect and localized rupture of the AuNM upon stretching; thus the stretchability is poor. A prestraining process is applied to suppress the localized rupture and has successfully improved the stretchability: electrical resistance of the prestrained AuNM exhibits modest change by one-time stretching to 160%, or repeated stretching to 50% for 25 000 cycles. This conductor is an ideal platform for robust stretchable photoelectronics. The idea of introducing a covalent bond to improve the scratch-resistance may also be applied to other systems including Ag nanowire films, carbon nanotube films, graphene, and so forth. PMID- 26674365 TI - Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions. AB - OBJECTIVE: Individuals are often infected with multiple genotypes of human papillomavirus (HPV) simultaneously, but the role these infections play in the development of cervical disease is not well established. This study aimed to determine the association of multiple HPV infections with high-risk cervical lesions (hrCLs). STUDY DESIGN: HPV genotyping was performed on 798 SurePath specimens collected between December 1, 2009, and April 30, 2011. The cases were classified as hrCL (n = 90) or non-hrCL (n = 708) based on cytology diagnoses. The association between hrCL and HPV infection patterns was analyzed. RESULTS: Multiple HPV infections were frequently encountered (38.2%) in the cohort. Increased frequency of hrCLs was associated with a single high-risk HPV (hrHPV) infection. An additive or synergistic effect was not observed for hrCL in multiple HPV infections. The hrCL rates appeared to decrease in various patterns of multiple HPV infections, but the reduction was not statistically significant. CONCLUSIONS: Multiple HPV infections are common with no additive or synergistic effect on the development of hrCL. Conversely, reduced hrCL rates were observed in various patterns of multiple HPV infections compared to their single-genotype infection counterparts, suggestive of possible intergenotypic competition or more effective immune response triggered by multiple infections. Further studies in larger cohorts are needed. PMID- 26674366 TI - EEG Abnormalities Are Associated With Poorer Depressive Symptom Outcomes With Escitalopram and Venlafaxine-XR, but Not Sertraline: Results From the Multicenter Randomized iSPOT-D Study. AB - Rationale Limited research is available on electrophysiological abnormalities such as epileptiform EEG or EEG slowing in depression and its association with antidepressant treatment response. Objectives We investigated the association between EEG abnormalities and antidepressant treatment response in the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Methods Of 1008 participants with major depressive disorder randomized to escitalopram, sertraline, or venlafaxine-XR, 622 completed 8 weeks of treatment per protocol. The study also recruited 336 healthy controls. Treatment response was established after 8 weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed. EEG abnormalities including epileptiform activity, EEG slowing, and alpha peak frequency (APF) were scored for all subjects, blind to treatment outcome. Results Patients and controls did not differ in the occurrence of EEG abnormalities. Furthermore, in the per protocol sample the occurrence of epileptiform EEG and EEG slowing (as a combined marker) were associated with a reduced likelihood of responding to escitalopram (P = .019; odds ratio [OR] = 3.56) and venlafaxine-XR (P = .043; OR = 2.76), but not sertraline (OR = 0.73). The response rates for this "any EEG abnormality" groups versus the "no abnormality" group were 33% and 64% for escitalopram and 41% and 66% for venlafaxine-XR, respectively. A slow APF was associated with treatment response only in the sertraline group (P = .21; d = .027). Conclusions EEG abnormalities are associated with nonresponse to escitalopram and venlafaxine-XR, but not sertraline, whereas a slow APF is associated to response for sertraline only. PMID- 26674367 TI - Substrate-Mediated Laser Ablation under Ambient Conditions for Spatially-Resolved Tissue Proteomics. AB - Numerous applications of ambient Mass Spectrometry (MS) have been demonstrated over the past decade. They promoted the emergence of various micro-sampling techniques such as Laser Ablation/Droplet Capture (LADC). LADC consists in the ablation of analytes from a surface and their subsequent capture in a solvent droplet which can then be analyzed by MS. LADC is thus generally performed in the UV or IR range, using a wavelength at which analytes or the matrix absorb. In this work, we explore the potential of visible range LADC (532 nm) as a micro sampling technology for large-scale proteomics analyses. We demonstrate that biomolecule analyses using 532 nm LADC are possible, despite the low absorbance of biomolecules at this wavelength. This is due to the preponderance of an indirect substrate-mediated ablation mechanism at low laser energy which contrasts with the conventional direct ablation driven by sample absorption. Using our custom LADC system and taking advantage of this substrate-mediated ablation mechanism, we were able to perform large-scale proteomic analyses of micro-sampled tissue sections and demonstrated the possible identification of proteins with relevant biological functions. Consequently, the 532 nm LADC technique offers a new tool for biological and clinical applications. PMID- 26674369 TI - Tributyltin promoted hepatic steatosis in zebrafish (Danio rerio) and the molecular pathogenesis involved. AB - Endocrine disruptor effects of tributyltin (TBT) are well established in fish. However, the adverse effects on lipid metabolism are less well understood. Since the liver is the predominant site of de novo synthesis of lipids, the present study uses zebrafish (Danio rerio) to examine lipid accumulation in the livers and hepatic gene expression associated with lipid metabolism pathways. After exposure for 90 days, we found that the livers in fish exposed to TBT were yellowish in appearance and with accumulation of lipid droplet, which is consistent with the specific pathological features of steatosis. Molecular analysis revealed that TBT induced hepatic steatosis by increasing the gene expression associated with lipid transport, lipid storage, lipiogenic enzymes and lipiogenic factors in the livers. Moreover, TBT enhanced hepatic caspase-3 activity and up-regulated genes related to apoptosis and cell-death, which indicated steatotic livers of fish exposed to TBT and the subsequent liver damage were likely due to accelerated hepatocyte apoptosis or cell stress. In short, TBT can produce multiple and complex alterations in transcriptional activity of lipid metabolism and cell damage, which provides potential molecular evidence of TBT on hepatic steatosis. PMID- 26674370 TI - Gas-Phase Spectroscopic Detection and Structural Elucidation of Carbon-Rich Group 14 Binary Clusters: Linear GeC3Ge. AB - Guided by high-level quantum-chemical calculations at the CCSD(T) level of theory, the first polyatomic germanium-carbon cluster, linear Ge2C3, has been observed at high spectral resolution in the gas phase through its remarkably complex fundamental antisymmetric C-C stretching mode nu3 located at 1932 cm(-1). The observation of a total of six isotopic species permits the derivation of a highly accurate value for the equilibrium Ge-C bond length. The present study suggests that many more Ge-C species might be detectable in the future using a combination of laser-ablation techniques for production and high-resolution infrared and/or microwave techniques for spectroscopic detection. PMID- 26674368 TI - The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes. AB - One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and alpha-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended. PMID- 26674373 TI - Brief Report: HIV-1 gp120 T-Cell Responses Correspond to Infection Outcomes in the Global iPrEx Chemoprophylaxis Trial. AB - Association of HIV-1-specific T-cell responses to infection risk in seronegative individuals is controversial. We quantified and phenotypically characterized gp120-specific T-cell responses in HIV-1 exposed, but uninfected subjects enrolled in the global Pre-exposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial. IFNgamma ELISpot responses were detected in 24% of subjects irrespective of infection outcome. HIV-1 gp120 envelope-specific T-cell responses were more uniformly IFN-gamma+TNF-alpha+Mip-1beta+ in persistently seronegative subjects relative to subjects who later seroconverted (median frequency of 76.5% and 66.5%, respectively). IFNgamma responses targeted the V2 loop for subjects who remained seronegative. HIV-1 gp120 envelope V2 loop specific CD8 T-cell responses may help to protect against HIV-1 acquisition. PMID- 26674372 TI - Feasibility, Acceptability, and Tolerability of Targeted Naltrexone for Nondependent Methamphetamine-Using and Binge-Drinking Men Who Have Sex with Men. AB - BACKGROUND: There are no effective pharmacologic strategies for nondependent methamphetamine (meth)-using and binge-drinking men who have sex with men (MSM) at high-risk for HIV. We sought to determine the feasibility of enrolling and retaining this population in a pharmacologic trial; the acceptability of pharmacotherapy study procedures; and the tolerability of targeted naltrexone versus placebo. METHODS: Thirty meth-using and binge-drinking MSM were randomly assigned 1:1 to 50 mg naltrexone or placebo for 8 weeks for targeted administration (ie, during craving or in anticipation of meth or alcohol use). Substance use counseling and behavioral assessments were conducted every 2 weeks. Medication use was measured using WisePill dispensers. RESULTS: Trial completion was 93%; visit completion rate was 95%. Mean weekly number of medication pills taken was 2.1 and was similar between arms. Participant satisfaction rate was 96%. There were neither serious adverse events nor differences in adverse event rates between arms. In exploratory intention-to-treat analyses, there were no differences in meth use and drinking. Naltrexone participants had greater reductions in serodiscordant receptive anal intercourse [incident rate ratio (IRR) = 0.15; 95% CI = 0.05 to 0.42] and serodiscordant condomless receptive anal intercourse (IRR = 0.11; 95% CI = 0.03 to 0.37), compared with placebo. In subgroup analyses among frequent meth users, naltrexone participants had greater reductions in meth-using days (IRR = 0.78; 95% CI = 0.62 to 0.99). In as-treated analyses, frequent study medication users in the naltrexone arm had greater reductions in binge drinking days (IRR = 0.72; 95% CI = 0.54 to 0.97). CONCLUSIONS: Targeted naltrexone is a feasible, acceptable, and tolerable intervention strategy for nondependent meth-using and binge-drinking MSM. Naltrexone was associated with significant sexual risk reductions; and for some individuals, naltrexone was associated with meth and binge-drinking reductions. PMID- 26674374 TI - Pattern and Trend of Morbidity in the Infectious Disease Ward of North Bengal Medical College and Hospital. AB - BACKGROUND: In spite of experiencing a large decline in the spread and burden of infectious diseases, the Global Burden of Disease Project suggests that about 30% of the disease burden in India is attributable to infections. The hospital data constitute a basic and primary source of information for continuous follow up of this changing pattern of morbidity and mortality. AIM: To identify the pattern and trend of different infectious diseases among admissions in the Infectious Disease ward of North Bengal Medical College and Hospital. MATERIALS AND METHODS: Retrospective analysis of inpatient hospital database over 5 years period (January 2008 - December 2012) of Infectious Disease ward of North Bengal Medical College & Hospital. RESULTS: Among 3277 admissions in the Infectious Disease ward during 2008-12, diarrhoeal diseases (84.3%) were most common. The highest mortality was recorded for rabies cases (83.9%), followed by tetanus (32.6%) and diphtheria (27.3%). The majority cases of diphtheria (78.9%) and measles (53.1%) belonged to below 9 years age. Except the year 2010, there was a gradual rise in admissions from 2008 to 2012. CONCLUSION: Review of hospital records provided information regarding the pattern of diseases but no definite trend among admissions in the infectious diseases ward. PMID- 26674375 TI - Electrochemical Behavior of TiO(x)C(y) as Catalyst Support for Direct Ethanol Fuel Cells at Intermediate Temperature: From Planar Systems to Powders. AB - To achieve complete oxidation of ethanol (EOR) to CO2, higher operating temperatures (often called intermediate-T, 150-200 degrees C) and appropriate catalysts are required. We examine here titanium oxycarbide (hereafter TiOxCy) as a possible alternative to standard carbon-based supports to enhance the stability of the catalyst/support assembly at intermediate-T. To test this material as electrocatalyst support, a systematic study of its behavior under electrochemical conditions was carried out. To have a clear description of the chemical changes of TiOxCy induced by electrochemical polarization of the material, a special setup that allows the combination of X-ray photoelectron spectroscopy and electrochemical measurements was used. Subsequently, an electrochemical study was carried out on TiOxCy powders, both at room temperature and at 150 degrees C. The present study has revealed that TiOxCy is a sufficiently conductive material whose surface is passivated by a TiO2 film under working conditions, which prevents the full oxidation of the TiOxCy and can thus be considered a stable electrode material for EOR working conditions. This result has also been confirmed through density functional theory (DFT) calculations on a simplified model system. Furthermore, it has been experimentally observed that ethanol molecules adsorb on the TiOxCy surface, inhibiting its oxidation. This result has been confirmed by using in situ Fourier transform infrared spectroscopy (FTIRS). The adsorption of ethanol is expected to favor the EOR in the presence of suitable catalyst nanoparticles supported on TiOxCy. PMID- 26674377 TI - Shaping Taste: The Molecular Discovery of Rice Genes Improving Grain Size, Shape and Quality. PMID- 26674376 TI - Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch. AB - RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein phosphatases PP1 and PP2A-B56 regulate the chromosome targeting of Aurora-B kinase and RepoMan, respectively. Here we show that this task division is critically dependent on the phosphorylation of RepoMan by protein kinase Cyclin-dependent kinase 1 (Cdk1), which reduces the binding of PP1 but facilitates the recruitment of PP2A-B56. The inactivation of Cdk1 in early anaphase reverses this phosphatase switch, resulting in the accumulation of PP1-RepoMan to a level that is sufficient to catalyse its own chromosome targeting in a PP2A-independent and irreversible manner. Bulk-targeted PP1-RepoMan also inactivates Aurora B and initiates nuclear envelope reassembly through dephosphorylation-mediated recruitment of Importin beta. Bypassing the Cdk1 regulation of PP1-RepoMan causes the premature dephosphorylation of its mitotic-exit substrates in prometaphase. Hence, the regulation of RepoMan-associated phosphatases by Cdk1 is essential for the timely dephosphorylation of their mitotic substrates. PMID- 26674378 TI - Enhanced Expression of miR-425 Promotes Esophageal Squamous Cell Carcinoma Tumorigenesis by Targeting SMAD2. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers in the world. Currently, clinical therapy of ESCC remains limited and the five-year survival rate is poor. The function of miR-425 has been reported in multiple human cancers. However, the tumorigenic role and clinical significance of miR-425 in ESCC remains unclear. We found that enhanced expression of miR-425 in ESCC cell lines not only promoted cell proliferation and colony formation, but also increased cellular metastasis. Furthermore, we revealed the mechanism that miR-425 inhibited the expression of SMAD2 by targeting the second binding site in the 3'-untranslated region (3'-UTR) in ESCC. This mode of action influenced not only SMAD2 mRNA expression but also protein expression. In addition, we detected the expression of miR-425 in ESCC tissues and plasma. Moreover, we analyzed the relationship between miR-425 expression and SMAD2 mRNA expression. We found that miR-425 was overexpressed in ESCC tissues and the plasma relative to adjacent normal tissues and plasma of healthy individuals. Furthermore, there was a negative correlation between miR-425 expression and SMAD2. Taken together, our results show that miR-425 functions as an oncogene by targeting the 3'-UTR of SMAD2 and indicate the potential utility of plasma miR-425 as a novel biomarker for ESCC diagnosis. PMID- 26674379 TI - Galphas Relays Sphingosine-1-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity. AB - Sphingosine-1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor (GPCR), controls vascular stability by stabilizing vascular endothelial (VE)-cadherin junctional localization and inhibiting vascular endothelial growth factor receptor 2 (VEGFR2) signaling. However, the molecular mechanisms that link S1PR1 signaling to intracellular effectors remain unknown. In this study, we demonstrate that the heterotrimeric G protein subfamily member Galphas, encoded by GNAS, acts as a relay mediator of S1PR1 signaling to control vascular integrity by stabilizing VE-cadherin at endothelial junctions. The endothelial cell-specific deletion of Galphas in mice causes early embryonic lethality with massive hemorrhage and a disorganized vasculature. The immunostaining results revealed that Galphas deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mural cell coverage of the vessels is not impaired. In addition, we found that Galphas depletion blocks the S1PR1-activation induced VE cadherin stabilization at junctions, supporting that Galphas acts downstream of S1PR1 signaling. Thus, our results demonstrate that Galphas is an essential mediator to relay S1PR1 signaling and maintain vascular integrity. PMID- 26674380 TI - Dynamic and Coordinated Expression Changes of Rice Small RNAs in Response to Xanthomonas oryzae pv. oryzae. AB - Endogenous small RNAs are newly identified players in plant immune responses, yet their roles in rice (Oryza sativa) responding to pathogens are still less understood, especially for pathogens that can cause severe yield losses. We examined the small RNA expression profiles of rice leaves at 2, 6, 12, and 24 hours post infection of Xanthomonas oryzae pv. oryzae (Xoo) virulent strain PXO99, the causal agent of rice bacterial blight disease. Dynamic expression changes of some miRNAs and trans-acting siRNAs were identified, together with a few novel miRNA targets, including an RLK gene targeted by osa-miR159a.1. Coordinated expression changes were observed among some small RNAs in response to Xoo infection, with small RNAs exhibiting the same expression pattern tended to regulate genes in the same or related signaling pathways, including auxin and GA signaling pathways, nutrition and defense-related pathways. These findings reveal the dynamic and complex roles of small RNAs in rice-Xoo interactions, and identify new targets for regulating plant responses to Xoo. PMID- 26674381 TI - Competitive Expression of Endogenous Wheat CENH3 May Lead to Suppression of Alien ZmCENH3 in Transgenic Wheat * Maize Hybrids. AB - Uniparental chromosome elimination in wheat * maize hybrid embryos is widely used in double haploid production of wheat. Several explanations have been proposed for this phenomenon, one of which is that the lack of cross-species CENH3 incorporation may act as a barrier to interspecies hybridization. However, it is unknown if this mechanism applies universally. To study the role of CENH3 in maize chromosome elimination of wheat * maize hybrid embryos, maize ZmCENH3 and wheat alphaTaCENH3-B driven by the constitutive CaMV35S promoter were transformed into wheat variety Yangmai 158. Five transgenic lines for ZmCENH3 and six transgenic lines for alphaTaCENH3-B were identified. RT-PCR analysis showed that the transgene could be transcribed at a low level in all ZmCENH3 transgenic lines, whereas transcription of endogenous wheat CENH3 was significantly up regulated. Interestingly, the expression levels of both wheat CENH3 and ZmCENH3 in the ZmCENH3 transgenic wheat * maize hybrid embryos were higher than those in the non-transformed Yangmai 158 * maize hybrid embryos. This indicates that the alien ZmCENH3 in wheat may induce competitive expression of endogenous wheat CENH3, leading to suppression of ZmCENH3 over-expression. Eliminations of maize chromosomes in hybrid embryos of ZmCENH3 transgenic wheat * maize and Yangmai 158 * maize were compared by observations on micronuclei presence, by marker analysis using maize SSRs (simple sequence repeats), and by FISH (fluorescence in situ hybridization) using 45S rDNA as a probe. The results indicate that maize chromosome elimination events in the two crosses are not significantly different. Fusion protein ZmCENH3-YFP could not be detected in ZmCENH3 transgenic wheat by either Western blotting or immnunostaining, whereas accumulation and loading of the alphaTaCENH3-B-GFP fusion protein was normal in alphaTaCENH3-B transgenic lines. As ZmCENH3-YFP did not accumulate after AM114 treatment, we speculate that low levels of ZmCENH3 protein in transgenic wheat may be one of the factors that lead to failure of suppression of maize chromatin elimination in ZmCENH3 transgenic wheat * maize hybrids. PMID- 26674382 TI - Digital Karyotyping with Whole Genomic Sequencing for Complex Congenital Disorder. PMID- 26674383 TI - Variation in Chromosome Constitution of the Xiaoyan Series Partial Amphiploids and Its Relationship to Stripe Rust and Stem Rust Resistance. PMID- 26674384 TI - Diagnostic anatomy and diagnostics of enthesal pathologies of the rotator cuff. AB - Detailed anatomy, crucial in modern high-definition diagnostics imaging, is a base for understanding diagnostic images and the nature of the diagnosed disease. THE AIM OF THIS PAPER: is presentation of a new anatomical model of the rotator cuff, which includes definition of tendinous and capsule-ligamentous layers as equally important to rotator cuff function understanding. Schematic and diagnostic (ultrasonography, magnetic resonance imaging) anatomy of the rotator cuff based on the core tendon concept is presented. Appropriate tissue layers of the cuff are discussed in detail. In the diagnostics part some enthesal pathologies of the rotator cuff are presented. MATERIAL AND METHODS: New anatomical data was analyzed in the context of rotator cuff layers - their presence, thickness and structure observed on magnetic resonance imaging and ultrasonographic images. CONCLUSIONS: Rotator cuff should be regarded as a multilayer structure consisting of fused fibers of tendons and capsuloligamentous complex. The thickness of these layers is comparable therefore it is important to realize that capsular pathologies may become a serious obstacle to normal shoulder joint function. Understanding of anatomical rotator cuff layers explains the formation of calcific cavities within the rotator cuff. In fact between layers of the cuff. Calcific cavities are a sequelae of chronic enthesopathy/enthesal tear with hydroxyapatite filling and probably delaminating the tendinous layer from the capsuloligamentous one. PMID- 26674385 TI - Exhaled nitric oxide in school children: Searching for the lost variability. AB - OBJECTIVE: The factors - including asthma and rhinoconjunctivitis - which influence FeNO values in a general population of school children have been studied in order to know to what extent the variability of those values can be explained. METHODS: FeNO was measured in a population of 240 school children aged 6-12 years by means of a Niox-MinoTM device in a standardised way. Parents filled in an ISAAC-validated questionnaire of symptoms and environmental factors. Diagnoses were checked against clinical records. Height and weight were measured. A multivariate regression analysis including all variables in the questionnaire was performed, which was followed by two Xi stepwise tests in order to build a predictive model which included the main variables influencing FeNO values. RESULTS: Among the 240 children, 10 suffered from asthma, 16 from rhinoconjunctivitis and 15 from both conditions. FeNO values (GM+/-GSD) in children with rhinoconjunctivitis (19.61+/-1.20ppb), with asthma (18.62+/ 1.32ppb), and with both conditions (17.62+/-1.19ppb) tended to be significantly higher than control children (11.42+/-1.04ppb), p=0.0016, p=0.08 and p=0.01, respectively. The different predictive models were able to explain only 20-27% of FeNO variability. CONCLUSIONS: The proportion of FeNO inter-individual variability which can be explained by individual (including suffering from asthma or rhinoconjunctivitis), family, and environmental factors is very low (20-27%). This could have implications on the usefulness of FeNO as a diagnostic tool in asthma. PMID- 26674387 TI - Huang PY, mactier S, armacki N, et al. Protein profiles distinguish stable and progressive chronic lymphocytic leukemia. Leuk lymphoma 2016;57:1033-1043. http://dx.doi.org/10.3109/10428194.2015.1094692. PMID- 26674386 TI - Physical Changes in Satsuma Mandarin Leaf after Infection of Elsinoe fawcettii Causing Citrus Scab Disease. AB - Citrus scab disease is one of the destructive diseases that reduce the value of fruit for the fresh market. We analyzed the process of symptom development after infection with scab pathogen Elsinoe fawcettii in the susceptible satsuma mandarin leaves to observe the structural modification against pathogen. The cuticle and epidermal cells along with 3-5 layers of mesophyll tissue were degraded 1-2 days post inoculation. Surrounding peripheral cells of degraded tissues grew rapidly and then enveloped the necrotic area along with the growing conidia. Cross sections through the lesion revealed hyphal colonization in epidermis and mesophyll tissues. In response to the pathogen colonization, host cell walls were lignified, inner cells were rapidly compartmentalized and a semi circular boundary was formed that separated the infected region from the non infected region, and finally prevented the intercellular pathogen spread. PMID- 26674388 TI - Ghrelin response to hedonic eating in underweight and short-term weight restored patients with anorexia nervosa. AB - Recently, anorexia nervosa (AN) has been conceptualized as a reward-related disorder, and alterations in brain reward processes have been documented in both acute and recovered AN patients. However, the role of endogenous biochemical mediators, such as ghrelin, in the modulation of reward processes has been poorly investigated in this eating disorder. Hedonic eating, that is the consumption of food exclusively for pleasure and not to maintain energy homeostasis, is a useful paradigm to investigate the physiology of food-related reward. Therefore, we assessed the response of peripheral ghrelin to hedonic eating in 7 underweight and 7 recently weight-restored AN patients and compared it to that of previously studied healthy controls. We found that in satiated underweight patients with AN plasma ghrelin levels progressively decreased after the exposure and the consumption of both the favorite and unfavorite food whereas in satiated weight restored AN patients and satiated healthy controls plasma ghrelin concentrations significantly increased after the exposure to the favorite food and after eating it, but decreased after the unfavorite food. These results suggest a derangement in the ghrelin modulation of food-related pleasurable and rewarding feelings, which might sustain the reduced motivation toward food intake of acute AN patients. PMID- 26674390 TI - Novel mechanism of ghrelin therapy for cachexia. PMID- 26674392 TI - Science, Death, and Consciousness. PMID- 26674389 TI - Cancer metabolism and oxidative stress: Insights into carcinogenesis and chemotherapy via the non-dihydrofolate reductase effects of methotrexate. AB - Methotrexate has been in use as an anti-cancer agent for over 60 years. Though inhibition of dihydrofolate reductase is its best known mechanisms of action, its non-dihydrofolate reductase dependent mechanisms disrupt metabolic pathways resulting in a depletion of NAD(P)H and increasing oxidative stress. These mechanisms highlight a novel dependence of cancer cells on their metabolic abnormalities to buffer oxidative stress and chemotherapeutic agents interfere with these cellular abilities. Mitochondria appear to play a significant role in maintaining cancer cell viability and alterations in metabolism seen in cancer cells aid this mitochondrial ability. Further research is needed to understand the effects of other chemotherapeutic agents on these pathways. PMID- 26674391 TI - Basic dissecting techniques in ultrasound-guided surgery. AB - Ultrasound-guided surgery is an area of minimally-invasive surgery where surgical procedures are performed with the aid of ultrasound imaging throghout the operation. This requires the operator to posses a certain degree of experience in endoscopic procedures, and to be adeptly skillfull in conducting US examinations. It is combining and finely tuning together these two elements that allows to perform efficiently an ultrasound-guided surgical procedure. Accessing an affected site correctly is of utmost importance in surgery, being oftentimes decisive in terms of the procedure's final outcome. In ultrasound-guided procedures, the operative site is accessed percutaneously, with a single point incision, yet tissues situated deeper within are dissected with dissecting techniques in a fluid evironment, typical for this area of surgery. Dissecting techniques in ultrasound-guided surgery are currently divided into basic ones which employ either a hydrodissection needle, surgical instruments, electrosurgical instruments, a thread, or a combination thereof, and advanced ones where either a balloon, a hook dissection technique, or a hybrid one is used. Hydrodissection with a needle was devised based on the rule of complementarity, and is the most frequently applied technique in ultrasound guided surgery. The immense possibilities that go along with this modality will be of huge benefit to any surgeon, regardless of their field. Dissection with a variety of surgical instruments and electrosurgery instruments is a standard practice in all surgery areas, yet the method of imaging we employ in ultrasound guided surgery results in certain modifications of these techniques. It is, however, learning the thread technique that facilitates a precise and oftentimes extensive dissection. This technique is successfully applied for dissecting muscle, ligament, tendon, vascular and other structures. Having mastered dissecting techniques allows to perform any minimally-invasive procedure efficiently, be they ultrasound-guided, artroscopic, or endoscopic ones. Various surgical techniques are bridged, resulting in applying the so-called hybrid ones. Their strength lies in excellent imaging results allowing to conduct a surgical procedure both in a body cavity and within a parenchymal organ. PMID- 26674393 TI - Effect of dietary inclusion of toasted guar (Cyamopsis tetragonoloba) meal as a source of protein on performance of White Leghorn layers. AB - Two experiments were conducted to study the effect of including toasted (120 degrees C/35 min) guar meal (GM, Cyamopsis tetragonoloba) in the diet on performance and egg shell quality of White Leghorn (WL) layers. Totals of 2376 and 2816 layer chickens (Babcock, BV 300) were randomly distributed into 27 and 32 replicates with 88 birds each in Experiments 1 and 2, respectively. Three diets in Experiment 1 (0, 50 and 100 g GM) and 4 diets in Experiment 2 (0, 50, 100 and 150 g GM/kg) were prepared having similar concentrations of energy and protein. Each diet was fed ad libitum to 9 and 8 replicates, respectively, in Experiments 1 (from 53 to 68 weeks) and 2 (35 to 46 weeks of age). Compared to soya bean meal (SBM) GM contained similar concentrations of protein, but was deficient in all essential amino acids except arginine, which was 70% higher than in SBM. Total non-starch polysaccharide (NSP) content in GM (166 g/kg) was lower than that of SBM (179 g/kg). Amongst different NSP fractions, GM contained higher levels of arabans, xylans, mannans and glucans compared to SBM. The galactomannan gum content in GM was 46 g/kg. Egg production (EP), body weight (BW), food intake (FI), food efficiency (FE) and egg quality (shell weight, shell per cent, shell thickness, Haugh unit score, egg density and egg breaking strength) parameters were not affected by incorporating GM up to 100 g/kg diet in Experiment 1. However, egg weight (EW) and egg mass (EM) were reduced significantly in groups fed on 100 g/kg diet. In Experiment 2, EP and FE were not affected by incorporating GM up to 100 g/kg, but were reduced at 150 g/kg diet. FI, EW, BW and egg quality parameters were not affected by incorporating toasted GM up to 150 g/kg diet. Based on the results of both experiments, it is concluded that toasted GM can be included in WL layer diets up to 100 g/kg without affecting EP, FE, EW, EM, Haugh unit score, BW and egg shell quality parameters. PMID- 26674394 TI - Strong, Multi-Scale Heterogeneity in Earth's Lowermost Mantle. AB - The core mantle boundary (CMB) separates Earth's liquid iron outer core from the solid but slowly convecting mantle. The detailed structure and dynamics of the mantle within ~300 km of this interface remain enigmatic: it is a complex region, which exhibits thermal, compositional and phase-related heterogeneity, isolated pockets of partial melt and strong variations in seismic velocity and anisotropy. Nonetheless, characterising the structure of this region is crucial to a better understanding of the mantle's thermo-chemical evolution and the nature of core mantle interactions. In this study, we examine the heterogeneity spectrum from a recent P-wave tomographic model, which is based upon trans-dimensional and hierarchical Bayesian imaging. Our tomographic technique avoids explicit model parameterization, smoothing and damping. Spectral analyses reveal a multi-scale wavelength content and a power of heterogeneity that is three times larger than previous estimates. Inter alia, the resulting heterogeneity spectrum gives a more complete picture of the lowermost mantle and provides a bridge between the long wavelength features obtained in global S-wave models and the short-scale dimensions of seismic scatterers. The evidence that we present for strong, multi scale lowermost mantle heterogeneity has important implications for the nature of lower mantle dynamics and prescribes complex boundary conditions for Earth's geodynamo. PMID- 26674396 TI - Adaptive Measurement of Well-Being: Maximizing Efficiency and Optimizing User Experience during Individual Assessment. AB - Well-being is linked to important societal factors such as health care costs and productivity and has experienced a surge in development activity of both theories and measurement. This study builds on validation of the Well-Being 5 survey and for the first time applies Item Response Theory, a modern and flexible measurement paradigm, to form the basis of adaptive population well-being measurement. Adaptive testing allows survey questions to be administered selectively, thereby reducing the number of questions required of the participant. After the graded response model was fit to a sample of size N = 12,035, theta scores were estimated based on both the full-item bank and a simulation of Computerized Adaptive Testing (CAT). Comparisons of these 2 sets of score estimates with each other and of their correlations with external outcomes of job performance, absenteeism, and hospital admissions demonstrate that the CAT well-being scores maintain accuracy and validity. The simulation indicates that the average survey taker can expect a reduction in number of items administered during the CAT process of almost 50%. An increase in efficiency of this extent is of considerable value because of the time savings during the administration of the survey and the potential improvement of user experience, which in turn can help secure the success of a total population-based well-being improvement program. (Population Health Management 2016;19:284-290). PMID- 26674395 TI - Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats. AB - BACKGROUND: In a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization. METHODS: Using an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 MUg/mL or 5 MUg/mL. We intravitreally injected 0.1 MUg/mL or 5 MUg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays. RESULTS: Human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 MUg/mL (P<0.05), while 5 MUg/mL netrin-1 had an opposite effect (P<0.05) in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b-waves (a-wave: 0.1 MUg/mL netrin-1 =17.67+/ 3.39 MUm, 5 MUg/mL netrin-1 =28.50+/-1.31 MUm, phosphate-buffered saline [PBS] treated =17.67+/-3.39 MUm; b-wave: 0.1 MUg/mL netrin-1 =44.67+/-4.80 MUm, 5 MUg/mL netrin-1 =97.17+/-9.63 MUm, PBS-treated =44.67+/-4.80 MUm) and the expression of VEGF-A (no-treatment rats, 9.29+/-0.80 pg/mL; PBS-treated rats, 19.64+/-3.77 pg/mL; 0.1 MUg/mL netrin-1 treated rats, 21.37+/-3.64 pg/mL; 5 MUg/mL netrin-1 treated rats, 9.85+/-0.54 pg/mL, at 6 weeks after induction). By comparing fluoresce in angiography, level of inner blood retinal barrier breakdown (% of control), retinal hematoxylin-eosin staining, and collagen-IV fluorescence assays in the retinas of PBS-treated rats, netrin-1 was found to suppress and reverse retinal neovascularization at a concentration of 5 MUg/mL (P<0.05), while 0.1 MUg/mL netrin-1 (P<0.05) led to an increase in the number of new retinal blood vessels, after 6 weeks' injection. CONCLUSION: Netrin-1 could play a significant role in retinal neovascularization by dual-direction regulating angiogenesis dependent on dosage. PMID- 26674397 TI - Antibiotics Use and Misuse in Children: A Knowledge, Attitude and Practice Survey of Parents in India. AB - INTRODUCTION: Antibiotic resistance is a topic of global concern these days. Irrational, excessive use of antibiotics by the general public is one of the key factors responsible for this. AIM: Through this study, we aim to analyse the knowledge, attitude and practices of antibiotics use among parents of children presenting to a tertiary care hospital in India. Also, correlate it with the gender, education level and previous use of antibiotics by the parents. MATERIALS AND METHODS: A cross sectional study was conducted at a tertiary care hospital in Navi Mumbai, India from September to November 2014 and a total of 1000 parents were interviewed using a questionnaire designed by the authors. Descriptive statistics were used for the analysis of data. RESULTS: A total of 872 parents were included in the study. Around one in every four (28%) parents correctly identified that antibiotics are used against bacterial infections while only 15.5% parents knew the meaning of the term antibiotic resistance. Majority of the respondents appreciated that unnecessary use of antibiotics could harm the child (73.6%). It was noteworthy that 85.2% parents stated that they don't use leftover antibiotics from the previous prescription for the next time without doctor's consult. Males, parents with higher level of formal education and use of antibiotics previously were found to have more knowledge regarding antibiotics and lesser misconceptions (p<0.05). CONCLUSION: Overall, in this study it was found that misconceptions exist about the use and indications of antibiotics. Lack of knowledge regarding antibiotic resistance was prevalent. But participants were aware of the risks associated with use of excessive antibiotics. More interaction with paediatricians and involvement of mass media may help to improve the antibiotics knowledge and practices among parents and consequently, control the problem of antibiotic resistance. PMID- 26674398 TI - Seat pan and backrest pressure distribution while sitting in office chairs. AB - Nowadays, an increasing amount of time is spent seated, especially in office environments, where sitting comfort and support are increasingly important due to the prevalence of musculoskeletal disorders. The aim of this study was to develop a methodology for chair-specific sensor mat calibration, to evaluate the interconnections between specific pressure parameters and to establish those that are most meaningful and significant in order to differentiate pressure distribution measures between office chairs. The shape of the exponential calibration function was highly influenced by the material properties and geometry of the office chairs, and therefore a chair-specific calibration proved to be essential. High correlations were observed between the eight analysed pressure parameters, whereby the pressure parameters could be reduced to a set of four and three parameters for the seat pan and the backrest respectively. In order to find significant differences between office chairs, gradient parameters should be analysed for the seat pan, whereas for the backrest almost all parameters are suitable. PMID- 26674399 TI - Effects of overhead work configuration on muscle activity during a simulated drilling task. AB - Overhead work is a known catalyst for occupational shoulder injury. Industrial workers must often adopt awkward overhead postures and loading profiles to complete required tasks, potentially elevating injury risk. This research examined the combined influence of multiple overhead working parameters on upper extremity muscular demands for an industrial drilling application. Twenty-two right-handed males completed 24 unilateral and bilateral overhead work exertions stratified by direction (upward, forward), point of force application (15, 30 and 45 cm in front of the body), and whole-body posture (seated, standing). The dependency of electromyographic (EMG) activity on several factors was established. Significant two-way interactions existed between point of force application and direction (p < 0.0001) and direction and whole body posture (p < 0.0001). An average increase in muscular activity of 6.5% maximal voluntary contraction (MVC) occurred for the contralateral limb when the bilateral task was completed, compared to unilateral tasks, with less than a 1% MVC increase for the active limb. These findings assist evidence-based approaches to overhead tasks, specifically in the construction industry. A bilateral task configuration is recommended to reduce glenohumeral stability demands. As well, particularly for tasks with a far reach distance, design tasks to promote a forward directed exertion. The considerable inter-subject variability suggests that fixed heights are not ideal, and should be avoided, and where this is not possible reaches should be reduced. PMID- 26674400 TI - Effects of EVA gloves on grip strength and fatigue under low temperature and low pressure. AB - OBJECTIVE: To study the effects of wearing extravehicular activity (EVA) gloves on grip strength and fatigue in low temperature, low pressure and mixing of two factors (low temperature and low pressure). METHODS: The maximum grip strength and fatigue tests were performed with 10 healthy male subjects wearing gloves in a variety of simulated environments. The data was analysed using the normalization method. RESULTS: The results showed that wearing gloves significantly affected the maximum grip strength and fatigue. Pressure (29.6, 39.2 kPa) had more influence on the maximum grip compared with control group while low temperatures (-50, -90, -110 degrees C) had no influence on grip but affected fatigue dramatically. The results also showed that the maximum grip strength and fatigue were influenced significantly in a compound environment. CONCLUSIONS: Space environment remarkably reduced strength and endurance of the astronauts. However, the effects brought by the compound environment cannot be understood as the superimposition of low temperature and pressure effects. PMID- 26674401 TI - Climatic and psychosocial risks of heat illness incidents on construction site. AB - The study presented in this paper aims to identify prominent risks leading to heat illness in summer among construction workers that can be prioritised for developing effective interventions. Samples are 216 construction workers' cases at the individual level and 26 construction projects cases at the organisation level. A grounded theory is generated to define the climatic heat and psychosocial risks and the relationships between risks, timing and effectiveness of interventions. The theoretical framework is then used to guide content analysis of 36 individual onsite heat illness cases to identify prominent risks. The results suggest that heat stress risks on construction site are socially constructed and can be effectively managed through elimination at supply chain level, effective engineering control, proactive control of the risks through individual interventions and reactive control through mindful recognition and response to early symptoms. The role of management infrastructure as a base for effective interventions is discussed. PMID- 26674402 TI - Evaluation of load carriage systems used by active duty police officers: Relative effects on walking patterns and perceived comfort. AB - OBJECTIVES: This study aimed to examine the effects of two different load carriage systems on gait kinematics, temporospatial gait parameters and self reported comfort in Swedish police. METHODS: 21 active duty police officers were recruited for this crossover study design. Biomechanical and self-report data was collected on two testing occasions. On occasion 1, three dimensional kinematic data was collected while police wore a/no equipment (control), b/their standard issues belt and ballistic protection vest and c/a load bearing vest with ballistic protection vest. Police then wore the load bearing vest for a minimum of 3 months before the second testing occasion. RESULTS: The load bearing vest was associated with a significant reduction in range of motion of the trunk, pelvis and hip joints. Biomechanical changes associated with the load bearing vest appeared to reduce with increased wear time. In both the standard issue belt condition and the load bearing vest condition, police walked with the arms held in a significantly greater degree of abduction. Self-report data indicated a preference for the load bearing vest. CONCLUSION: The two load carriage designs tested in this study were found to significantly alter gait kinematics. The load bearing vest design was associated with the greatest number of kinematic compensations however these reduced over time as police became more accustomed to the design. Results from this study do not support selection of one load carriage design over the other and providing individuals with the option to choose a load carriage design is considered appropriate. PMID- 26674404 TI - An integrated biomechanical modeling approach to the ergonomic evaluation of drywall installation. AB - Three different methodologies: work sampling, computer simulation and biomechanical modeling, were integrated to study the physical demands of drywall installation. PATH (Posture, Activity, Tools, and Handling), a work-sampling based method, was used to quantify the percent of time that the drywall installers were conducting different activities with different body segment (trunk, arm, and leg) postures. Utilizing Monte-Carlo simulation to convert the categorical PATH data into continuous variables as inputs for the biomechanical models, the required muscle contraction forces and joint reaction forces at the low back (L4/L5) and shoulder (glenohumeral and sternoclavicular joints) were estimated for a typical eight-hour workday. To demonstrate the robustness of this modeling approach, a sensitivity analysis was conducted to examine the impact of some quantitative assumptions that have been made to facilitate the modeling approach. The results indicated that the modeling approach seemed to be the most sensitive to both the distribution of work cycles for a typical eight-hour workday and the distribution and values of Euler angles that are used to determine the "shoulder rhythm." Other assumptions including the distribution of trunk postures did not appear to have a significant impact on the model outputs. It was concluded that the integrated approach might provide an applicable examination of physical loads during the non-routine construction work, especially for those operations/tasks that have certain patterns/sequences for the workers to follow. PMID- 26674403 TI - Validity and reliability of pressure-measurement insoles for vertical ground reaction force assessment in field situations. AB - This study aimed to test the validity and reliability of pressure-measurement insoles (medilogic(r) insoles) when measuring vertical ground reaction forces in field situations. Various weights were applied to and removed from the insoles in static mechanical tests. The force values measured simultaneously by the insoles and force plates were compared for 15 subjects simulating work activities. Reliability testing during the static mechanical tests yielded an average interclass correlation coefficient of 0.998. Static loads led to a creeping pattern of the output force signal. An individual load response could be observed for each insole. The average root mean square error between the insoles and force plates ranged from 6.6% to 17.7% in standing, walking, lifting and catching trials and was 142.3% in kneeling trials. The results show that the use of insoles may be an acceptable method for measuring vertical ground reaction forces in field studies, except for kneeling positions. PMID- 26674405 TI - The effect of rest break schedule on acute low back pain development in pain and non-pain developers during seated work. AB - A significant portion of the population (25-50%) is known to develop acute low back pain (LBP) within a bout of prolonged sitting. Previous research has supported the use of frequent rest breaks, from seated office work, in order to reduce self-reported LBP, however, there is limited consensus about the recommended frequency and duration of rest breaks. This may be due to the limited consideration of individual differences in acute LBP development. The purpose of this study was to examine the effect of three different standing rest-break conditions on a group of pain developers (PD) and non-pain developers (NPD) engaged in prolonged seated work. Twenty participants completed four one-hour long bouts of seated typing: Condition A - no rest; Condition B - 5 min of standing rest every 30 min; Condition C - 2.5 min of standing rest every 15 min; Condition D - 50 s of standing rest every 5 min. Self-reported LBP, self-reported mental fatigue and 30-s samples of EMG were collected every 10 min throughout each session. Eight out of 20 participants (40%) reported LBP during Condition A (classified as PD). Only PD demonstrated clinically relevant increases in LBP across conditions where Conditions B, C, or D provided some relief, but did not restore pain scores to their original level, prior to sitting. PD and NPD developed mental fatigue equally, with Conditions B and D helping to reduce fatigue. No differences in productivity were observed between conditions or groups and no main effects were observed for muscle activity, median power frequency or co-contraction. These data suggests that frequent, short, standing rest breaks may help to reduce symptoms of LBP, however they are only a temporary solution as PD still developed clinically important LBP, even with frequent rest breaks. PMID- 26674406 TI - Intrinsic movement variability at work. How long is the path from motor control to design engineering? AB - For several years, increasing numbers of studies have highlighted the existence of movement variability. Before that, it was neglected in movement analysis and it is still almost completely ignored in workstation design. This article reviews motor control theories and factors influencing movement execution, and indicates how intrinsic movement variability is part of task completion. These background clarifications should help ergonomists and workstation designers to gain a better understanding of these concepts, which can then be used to improve design tools. We also question which techniques--kinematics, kinetics or muscular activity--and descriptors are most appropriate for describing intrinsic movement variability and for integration into design tools. By this way, simulations generated by designers for workstation design should be closer to the real movements performed by workers. This review emphasises the complexity of identifying, describing and processing intrinsic movement variability in occupational activities. PMID- 26674407 TI - A human factors approach to snowsport safety: Novel research on pediatric participants' behaviors and head injury risk. AB - OBJECTIVE: This study applied a human factors approach to snowsport resort systems to contribute to the understanding of the incidence and severity of pediatric snowsport head accelerations. BACKGROUND: Previous research indicates low magnitude head accelerations are common among snowsport participants. This study adds to the knowledge of snowsport safety by measuring aspects of participants' snowsport behavior and linking this with head acceleration data. METHOD: School-aged students (n = 107) wore telemetry-fitted helmets and Global Positioning System (GPS) devices during snowsport activity. Data was collected over 159 sessions (total hours 701). Head accelerations recorded by the telemetry units were compared with GPS-generated data. RESULTS: This study found speeds attained normally exceed the testing rating for which helmets are designed; lower rates of head accelerations compared to earlier studies and that when head accelerations did occur they were generally below the threshold for concussions. CONCLUSION: Pediatric snowsport head accelerations are rare and are generally of low magnitude. Those most at risk of a head acceleration >40 g were male snowboarders. Given the recorded speeds in first time participants, increased targeting of novice snowsport participants to encourage education about the use of protective equipment, including helmets, is warranted. Post event recall was not a good indicator of having experienced a head impact. Consideration should be given to raising the standard design speed testing for snowsport helmet protective devices to reflect actual snowsport behaviors. PMID- 26674408 TI - Correction factors for assessing immersion suits under harsh conditions. AB - Many immersion suit standards require testing of thermal protective properties in calm, circulating water while these suits are typically used in harsher environments where they often underperform. Yet it can be expensive and logistically challenging to test immersion suits in realistic conditions. The goal of this work was to develop a set of correction factors that would allow suits to be tested in calm water yet ensure they will offer sufficient protection in harsher conditions. Two immersion studies, one dry and the other with 500 mL of water within the suit, were conducted in wind and waves to measure the change in suit insulation. In both studies, wind and waves resulted in a significantly lower immersed insulation value compared to calm water. The minimum required thermal insulation for maintaining heat balance can be calculated for a given mean skin temperature, metabolic heat production, and water temperature. Combining the physiological limits of sustainable cold water immersion and actual suit insulation, correction factors can be deduced for harsh conditions compared to calm. The minimum in-situ suit insulation to maintain thermal balance is 1.553 0.0624.TW + 0.00018.TW(2) for a dry calm condition. Multiplicative correction factors to the above equation are 1.37, 1.25, and 1.72 for wind + waves, 500 mL suit wetness, and both combined, respectively. Calm water certification tests of suit insulation should meet or exceed the minimum in-situ requirements to maintain thermal balance, and correction factors should be applied for a more realistic determination of minimum insulation for harsh conditions. PMID- 26674409 TI - Influence of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing. AB - PURPOSE: The present study was an attempt to investigate the effect of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing. METHODS: Ten healthy subjects were recruited to stand for 2 h in three footwear conditions: barefoot, flat-bottomed shoe and unstable shoe. During standing, lower leg discomfort and EMG activity of medial gastrocnemius (MG) and tibialis anterior (TA) muscles were continuously monitored. Changes in lower leg volume over standing time also were measured. RESULTS: Lower leg discomfort rating reduced significantly while subjects standing on unstable shoe compared to the flat-bottomed shoe and barefoot condition. For lower leg volume, less changes also were observed with unstable shoe. The activity level and variation of right MG muscle was greater with unstable shoe compared to the other footwear conditions; however regarding the left MG muscle, significant difference was found between unstable shoe and flat bottomed shoe only for activity level. Furthermore no significant differences were observed for the activity level and variation of TA muscles (right/left) among all footwear conditions. CONCLUSIONS: The findings suggested that prolonged standing with unstable footwear produces changes in lower leg muscles activity and leads to less volume changes. Perceived discomfort also was lower for this type of footwear and this might mean that unstable footwear can be used as ergonomic solution for employees whose work requires prolonged standing. PMID- 26674410 TI - Evaluation of four sensor locations for physical activity assessment. AB - Direct measurements of physical activity (PA) obtained with inertial measurement units (IMUs) secured to the upper arms and trunk of 36 registered nurses working a full shift were compared to measurements obtained with a commercially-available PA monitor (ActiGraph wGT3X-BT) worn at the waist. Raw accelerations from each device were summarized into PA counts/min and metabolic equivalent (METs) categories using standard definitions. Differences between measurements were examined using repeated measures one-way analyses of variance (ANOVA) and agreement was assessed using Bland-Altman plots. Statistically significant differences were observed between all sensor locations for all PA summary metrics except for between the left and right arm for percentages of work time in the light and moderate counts/min categories. Bland-Altman plots suggested limited agreement between measurements obtained with the IMUs and measurements obtained with the wGT3X-BT waist-worn PA monitor. Results indicate that PA measurements vary substantially based on sensor location. PMID- 26674412 TI - Psychometric Properties of a New HIV/AIDS Knowledge Measure for Adults. AB - The aim of this study was to develop a new 29-item HIV/AIDS knowledge measure and to examine its psychometric properties for three samples of adults: non-HIV positive heterosexual people, non-HIV-positive men who have sex with men (MSM), and people living with HIV/AIDS (PLWHA). The authors collected data using an online questionnaire. A total of 9,349 Italian individuals agreed to participate in the study: 694 individuals (7.4%) were PLWHA, 5,232 (56.0%) were HIV negative, and the remaining 3,423 (36.6%) were MSM. Using two-parameter item response theory analysis, a bifactor model was found to be better fitting than a one factor model or a 12 correlated first-order factor model. Differential item functioning showed evidence of measurement nonequivalence of the instrument for the three samples of adults. The reliability of HIV/AIDS knowledge scale among PLWHA was satisfactory. Criterion-related validity was only achieved among non HIV-positive heterosexual people, non-HIV-positive MSM, as the HIV/AIDS knowledge scale was related with attitudes toward condom use, condom use with casual partners, unknown HIV status of partner, and HIV stigma. Among non-HIV-positive heterosexual people, the HIV/AIDS knowledge scale adds to the prediction of condom use above that of attitudes toward condom use scale. The HIV/AIDS knowledge scale is especially discriminating at low to medium levels of knowledge. PMID- 26674411 TI - Targeting the indoleamine 2,3-dioxygenase pathway in cancer. AB - Tumor cells escape the immune surveillance system of the host through a process called immune tolerance. Immunotherapy targets molecules that serve as checks and balances in the regulation of immune response. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme, which through the process of tryptophan depletion exerts an immunosuppressive effect, facilitating immune escape of tumors. This review summarizes our current knowledge on IDO expression in malignancies, the IDO inhibitors that are currently available and those under clinical development. PMID- 26674413 TI - Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder. AB - Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen insula/operculum connectivity in OCD is discussed. PMID- 26674414 TI - RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA. AB - MicroRNAs (miRNAs) integrate with Argonaut (Ago) to create the RNA-induced silencing complex, and regulate gene expression by silencing target mRNAs. RNA editing of miRNA may affect miRNA processing, assembly of the Ago complex and target mRNA binding. However, the function of edited miRNA, assembled within the Ago complex, has not been extensively investigated. In this study, sequence analysis of the Ago complex of Marsupenaeus japonicus shrimp infected with white spot syndrome virus (WSSV) revealed that host ADAR (adenosine deaminase acting on RNA) catalysed A-to-I RNA editing of a viral miRNA (WSSV-miR-N12) at the +16 site. This editing of the non-seed sequence did not affect association of the edited miRNA with the Ago protein, but inhibited interaction between the miRNA and its target gene (wsv399). The WSSV early gene wsv399 inhibited WSSV infection. As a result, the RNA editing of miRNA caused virus latency. Our results highlight a novel example of miRNA editing in the miRNA-induced silencing complex. PMID- 26674415 TI - Naturally produced opsonizing antibodies restrict the survival of Mycobacterium tuberculosis in human macrophages by augmenting phagosome maturation. AB - This study investigated the hypothesis that serum antibodies against Mycobacterium tuberculosis present in naturally infected healthy subjects of a tuberculosis (TB) endemic area could create and/or sustain the latent form of infection. All five apparently healthy Indian donors showed high titres of serum antibodies against M. tuberculosis cell membrane antigens, including lipoarabinomannan and alpha crystallin. Uptake and killing of bacilli by the donor macrophages was significantly enhanced following their opsonization with antibody-rich, heat-inactivated autologous sera. However, the capability to opsonize was apparent for antibodies against some and not other antigens. High content cell imaging of infected macrophages revealed significantly enhanced colocalization of the phagosome maturation marker LAMP-1, though not of calmodulin, with antibody-opsonized compared with unopsonized M. tuberculosis. Key enablers of macrophage microbicidal action--proinflammatory cytokines (IFN gamma and IL-6), phagosome acidification, inducible NO synthase and nitric oxide- were also significantly enhanced following antibody opsonization. Interestingly, heat-killed M. tuberculosis also elevated these mediators to the levels comparable to, if not higher than, opsonized M. tuberculosis. Results of the study support the emerging view that an efficacious vaccine against TB should, apart from targeting cell-mediated immunity, also generate 'protective' antibodies. PMID- 26674416 TI - Transcriptional and phenotypical heterogeneity of Trypanosoma cruzi cell populations. AB - Trypanosoma cruzi has a complex life cycle comprising pools of cell populations which circulate among humans, vectors, sylvatic reservoirs and domestic animals. Recent experimental evidence has demonstrated the importance of clonal variations for parasite population dynamics, survival and evolution. By limiting dilution assays, we have isolated seven isogenic clonal cell lines derived from the Pan4 strain of T. cruzi. Applying different molecular techniques, we have been able to provide a comprehensive characterization of the expression heterogeneity in the mucin-associated surface protein (MASP) gene family, where all the clonal isogenic populations were transcriptionally different. Hierarchical cluster analysis and sequence comparison among different MASP cDNA libraries showed that, despite the great variability in MASP expression, some members of the transcriptome (including MASP pseudogenes) are conserved, not only in the life cycle stages but also among different strains of T. cruzi. Finally, other important aspects for the parasite, such as growth, spontaneous metacyclogenesis or excretion of different catabolites, were also compared among the clones, demonstrating that T. cruzi populations of cells are also phenotypically heterogeneous. Although the evolutionary strategy that sustains the MASP expression polymorphism remains unknown, we suggest that MASP clonal variability and phenotypic heterogeneities found in this study might provide an advantage, allowing a rapid response to environmental pressure or changes during the life cycle of T. cruzi. PMID- 26674418 TI - Association Between Air Temperature and Cancer Death Rates in Florida: An Ecological Study. AB - Proponents of global warming predict adverse events due to a slight warming of the planet in the last 100 years. This ecological study tests one of the possible arguments that might support the global warming theory - that it may increase cancer death rates. Thus, average daily air temperature is compared to cancer death rates at the county level in a U.S. state, while controlling for variables of smoking, race, and land elevation. The study revealed that lower cancer death rates were associated with warmer temperatures. Further study is indicated to verify these findings. PMID- 26674417 TI - Dual functionality of O-GlcNAc transferase is required for Drosophila development. AB - Post-translational modification of intracellular proteins with O-linked N acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. PMID- 26674419 TI - Acute Cyclophosphamide Hemorrhagic Myopericarditis: Dilemma Case Report, Literature Review and Proposed Diagnostic Criteria. AB - Cyclophosphamide is a potent DNA alkylating agent used in chemotherapy and immunosuppression. Although an old agent, its use in the present day has expanded for cases of refractory autoimmune disease. In this report, a case of haemorrhagic myopericarditis resulting from high-dose cyclophosphamide for chronic inflammatory demyelinating polyneuropathy is presented. The patient had no predisposing cardiovascular risk factors and a structurally normal heart on previous echocardiogram. Following administration of high-dose cyclophosphamide, the patient developed acute congestive heart failure. Serial echocardiography demonstrated pericardial effusion, myocardial thickening, and progressive right ventricular dysfunction. Histopathology on autopsy revealed acute myocardial necrosis, intra-myocardial extravasation of blood, fibrin, and fibrin-platelet microthrombi compatible with the diagnosis of haemorrhagic myopericarditis. The ante-mortem diagnostic dilemma is described to emphasize the need for pattern recognition and clinical criteria for diagnosis. Subsequent comprehensive literature review was performed to identify features that will facilitate earlier diagnosis of haemorrhagic myopericarditis by healthcare providers. PMID- 26674420 TI - Ultrasound quiz 2. PMID- 26674421 TI - Histone methyltransferases and demethylases: regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing family and the Jumonji C (JmjC) domain-containing family represent the major histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containing KMTs and JmjC domain containing KDMs balance the osteogenic and adipogenic differentiation of MSCs. PMID- 26674422 TI - Single CD271 marker isolates mesenchymal stem cells from human dental pulp. AB - Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow (BMSCs), adult MSCs are isolated from craniofacial tissues including dental pulp tissues (DPs) using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cells (DMSCs). In this study, we used different combinations of surface markers (CD51/CD140alpha, CD271, and STRO-1/CD146) to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells (DPCs) obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence activated cell sorting revealed that 27.3% of DPCs were CD51(+)/CD140alpha(+), 10.6% were CD271(+), and 0.3% were STRO-1(+)/CD146(+). Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271(+) DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271(+) DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine. PMID- 26674423 TI - Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers. AB - Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140alpha, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence activated cell sorting analysis revealed that 24% of PDLCs were CD51(+)/CD140alpha(+), 0.8% were CD271(+), and 2.4% were STRO-1(+)/CD146(+). Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271(+) DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine. PMID- 26674425 TI - Expression analysis of alpha-smooth muscle actin and tenascin-C in the periodontal ligament under orthodontic loading or in vitro culture. AB - alpha-smooth muscle actin (alpha-SMA) and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of alpha-SMA and tenascin-C was altered in the periodontal ligament (PDL) under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-beta1 (TGF-beta1) and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells (hPDLCs). The hPDLCs under higher tensile or compressive stress significantly increased their levels of alpha-SMA and tenascin C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in alpha-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time dependent variation of alpha-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading. PMID- 26674424 TI - The effects of interleukin-1beta in modulating osteoclast-conditioned medium's influence on gelatinases in chondrocytes through mitogen-activated protein kinases. AB - Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little is known regarding the influence of the signalling from bone. Additionally, the collagenases and stromelysin-1 are involved in cartilage catabolism through mitogen-activated protein kinase (MAPK) signalling, but the role of the gelatinases has not been elucidated. Here, we studied the influence of osteoclastic signals on chondrocytes by characterising the expression of interleukin-1beta (IL-1beta) induced gelatinases through MAPK signalling. We found that osteoclast-conditioned media attenuated the gelatinase activity in chondrocytes. However, IL-1beta induced increased levels of gelatinase activity in the conditioned media group relative to the mono-cultured chondrocyte group. More specifically, IL-1beta restored high levels of gelatinase activity in c-Jun N-terminal kinase inhibitor pretreated chondrocytes in the conditioned media group and led to lower levels of gelatinase activity in extracellular signal-regulated kinase or p38 inhibitor pretreated chondrocytes. Gene expression generally correlated with protein expression. Taken together, these results show for the first time that signals from osteoclasts can influence gelatinase activity in chondrocytes. Furthermore, these data show that IL-1beta restores gelatinase activity through MAPK inhibitors; this information can help to increase the understanding of the gelatinase modulation in articular cartilage. PMID- 26674426 TI - Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss. AB - Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1beta, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor kappaB ligand) and macrophage colony stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases. PMID- 26674428 TI - Epidemiological features of traumatic spinal cord injury in Chongqing, China. AB - OBJECTIVE: To describe the epidemiological characteristics and trends of traumatic spinal cord injury in Chongqing, China. STUDY DESIGN: Hospital-based retrospective research. SETTING: Xinqiao Hospital, Chongqing. METHODS: We reviewed medical records of 554 patients with traumatic spinal cord injury (TSCI) admitted to Xinqiao Hospital from 2009 to 2013. Variables included gender, age, marital status, etiology, occupation, time of injury, level of injury, and severity of injury, the length of hospital stay, and treatment. RESULTS: The mean age of patients with TSCI was 45.6 +/- 13.8 years, and the male/female ratio was 4.33:1. 94.2% (522 patients) of all patients with TSCI were married. Falls, comprising low falls and high falls (10.8% and 50.9%, respectively), were the leading reason for a hospital visit. And the second reason was MVCs (21.8%). The most common injury site was the cervical spinal cord, accounting for nearly more than 54%. The length of hospital stay ranged between 1 and 219 days (mean: 28.3 days). The proportions of complete tetraplegia, incomplete tetraplegia, complete paraplegia and incomplete paraplegia were 17.1%, 37.8%, 22.2%, and 22.9%, respectively. CONCLUSION: The result revealed that the proportion of males was higher, as well as falls and MVCs were the first two main reasons, with older mean age of patients with TSCI than other countries. The occupations with highest risk for TSCI were peasants and laborers. All of these results prompted that preventive methods should be based on the characteristics of different type of patients with TSCI. PMID- 26674427 TI - Osteoblast integration of dental implant materials after challenge by sub gingival pathogens: a co-culture study in vitro. AB - Sub-gingival anaerobic pathogens can colonize an implant surface to compromise osseointegration of dental implants once the soft tissue seal around the neck of an implant is broken. In vitro evaluations of implant materials are usually done in monoculture studies involving either tissue integration or bacterial colonization. Co-culture models, in which tissue cells and bacteria battle simultaneously for estate on an implant surface, have been demonstrated to provide a better in vitro mimic of the clinical situation. Here we aim to compare the surface coverage by U2OS osteoblasts cells prior to and after challenge by two anaerobic sub-gingival pathogens in a co-culture model on differently modified titanium (Ti), titanium-zirconium (TiZr) alloys and zirconia surfaces. Monoculture studies with either U2OS osteoblasts or bacteria were also carried out and indicated significant differences in biofilm formation between the implant materials, but interactions with U2OS osteoblasts were favourable on all materials. Adhering U2OS osteoblasts cells, however, were significantly more displaced from differently modified Ti surfaces by challenging sub-gingival pathogens than from TiZr alloys and zirconia variants. Combined with previous work employing a co-culture model consisting of human gingival fibroblasts and supra-gingival oral bacteria, results point to a different material selection to stimulate the formation of a soft tissue seal as compared to preservation of osseointegration under the unsterile conditions of the oral cavity. PMID- 26674429 TI - Current Options for the Diagnosis, Staging and Therapeutic Management of Colorectal Cancer. AB - BACKGROUND: Colorectal cancer (CRC) is the one of the most common malignancies and is a leading cause of cancer death worldwide. The incidence of mortality from CRC has decreased in Western countries because of earlier diagnosis and improved treatment modalities; however, mortality is still increasing in most other regions of the world. SUMMARY: Progress in the development of imaging modalities has enabled more accurate staging based on the TNM classification. The therapeutic management of CRC should involve a multi-modal approach, including high-quality surgery and an optimal choice of chemotherapy and radiotherapy regimens according to disease characteristics and patient preferences. Even in the case of metastatic disease, the optimal multi-modal treatments could achieve potential cure or long-term survival benefit in some patients. The aim of this review is to present current options regarding the diagnosis, staging and treatment management for CRC based on published research reports and the current management guidelines. PMID- 26674440 TI - Vertebral anomalies accompanying Robinow syndrome. PMID- 26674441 TI - Vertebral compression fracture within a solid fusion mass without trauma after removal of pedicle screws. AB - BACKGROUND CONTEXT: Many complications of lumbar fusion have been reported. However, reports of complications related to implant removal after solid fusion are rare. In addition, there are almost no reports of compression fractures occurring within a fusion mass. PURPOSE: This work aimed to report a case of vertebral body compression fracture within a solid lumbar fusion mass after removal of fusion instrumentation, and to investigate the contributing factors. STUDY DESIGN: A case report was carried out. METHODS: A 67-year-old woman presented with gait disturbance and pain radiating from both lower extremities. She had a history of lumbar fusion at L2-L5 because of degenerative stenosis. We found spinal stenosis at L5-S1 and ossification of the ligamentum flavum at T12 L2. Posterior decompression and fusion were performed for the lesion, and previously inserted fusion instrumentation was removed at L2-L5 in accordance with the patient's request. After surgery, her symptoms decreased and she was discharged. Five weeks after surgery, the patient returned with sudden, severe back pain that occurred without trauma. Compression fracture at the L3 lower end plate was observed via magnetic resonance imaging. We treated her back pain with analgesics and a thoracolumbosacral orthosis. After 2 weeks, her back pain had decreased, and she was discharged. RESULTS: Before removal of instrumentation, we verified complete union using computed tomography. However, an unexpected compression fracture occurred within the fusion mass, without trauma. We suspect that the causes of the compression fracture were the straight sagittal imbalance of the spine, the cantilever motion in the anterior disc after posterior fusion, and decreased bone strength. CONCLUSIONS: Vertebral compression fracture in a solid fusion mass may occur as a complication of implant removal. Surgeons must take care to maintain normal sagittal alignment during spinal fusion, and they should consider careful removal of instrumentation for patients with risk factors such as osteoporosis, sagittal imbalance, long spine fusion, and certain types of fusion. PMID- 26674442 TI - Fatal cervical spine injuries: a Finnish nationwide register-based epidemiologic study on data from 1987 to 2010. AB - BACKGROUND CONTEXT: The number of cervical spine injuries (CSIs) is increasing. Cervical spine injuries are associated with high morbidity and mortality. Identifying those who are at risk for CSI-related death can help develop national and international interventions and policies to reduce mortality. PURPOSE: This study aimed to determine the trends in the incidence and the characteristics of fatal CSIs in Finland over a 24-year study period from 1987 to 2010. STUDY DESIGN/SETTING: A large nationwide, retrospective, register-based study was carried out. PATIENT SAMPLE: The population-based sample was collected from death certificates issued in Finland between 1987 and 2010. The death certificates were obtained from the official Cause-of-Death Register, coordinated by Statistics Finland, which covers all deaths occurring in Finland. OUTCOME MEASURES: Sociodemographics and injury- and death-related data were used for outcome measures. METHODS: All death certificates issued in Finland (1987-2010) containing a CSI as the cause of death were carefully reviewed. RESULTS: A total of 2,041 fatal CSIs were identified. These constituted 0.17% of all deaths in Finland within the study period. The average annual incidence of fatal CSIs was 16.5 per million (range: 12.5-21.2). The majority of the victims were male (72.9%) and had concurrent spinal cord injury (83.0%). Traffic accidents (40.1%) and falls (45.0%) were the most common injury mechanisms. Almost one-third (29.8%) of the deaths were alcohol-related. Among the young victims (<60 years) with upper CSI (C0-C2), the majority (91.8%) died within 24 hours post-injury. One-third of elderly victims' (>=60 years) CSI-related deaths occurred after 1 week post-injury and were mostly (74.2%) caused by respiratory and circulatory system diseases. Within the 24-year period, the incidence of fatal CSIs (+2/million), as well as the average age of sustaining a fatal CSI (+13.5 years), increased markedly. Fall-induced accidents among elderly males were the most prominently increasing subpopulation of fatal CSI victims. CONCLUSIONS: In recent decades, fatal CSI incidence (death certificate-based) has increased, being 18.6 per million in Finland in 2010. Victims of fatal CSIs tend to be older than in the past, and for a substantial number of males, low-energy falls lead to cervical trauma and death. PMID- 26674443 TI - Parasacral malignant fibrous histiocytoma presenting with low back pain. PMID- 26674444 TI - Pulmonary edema and hemorrhage after acute spinal cord injury in rats. AB - BACKGROUND CONTEXT: Respiratory complications are a major cause of morbidity and mortality during the first days after acute spinal cord injury (ASCI). However, the pathophysiology of respiratory insufficiency resulting from spinal cord injury that involves lower levels is less well understood. PURPOSE: The aim of the present study was to investigate pulmonary pathophysiology after ASCI. STUDY DESIGN: This is an experimental animal study of ASCI investigating pulmonary pathophysiology after ASCI. METHODS: Eighty-four (N=84) rats were divided into two groups: a sham surgery (n=42) and an injury group (n=42). In the injury group, ASCI was induced at the level of the tenth thoracic vertebra by a modified Allen method. Rats were sacrificed 6 hours, 12 hours, 24 hours, 3 days, 1 week, 2 weeks, and 4 weeks after surgery. Pulmonary edema was assessed by calculating the ratio of the wet-to-dry lung weight (W:D). Pulmonary edema and hemorrhage were evaluated by observing gross and microscopic morphology. The study was funded by Natural Science Foundation of China (NSFC, 81272172). The funder of the present study had no capacity to influence the scholarly conduct of the research, interpretation of results, or dissemination of study outcomes. RESULTS: In the injury group, W:D was significantly increased 12 hours after surgery compared with the sham surgery group; W:D peaked 3 days after ASCI (p<.05). Gross morphologic observations showed hemorrhagic lesions on the lung tissue 12 hours after ASCI and pulmonary edema 24 hours after ASCI. Pulmonary edema peaked 3 days after ASCI and was obviously decreased 1 week after ASCI. Hemorrhage was apparent until 2 weeks after ASCI. Light microscopy showed congestion of pulmonary capillaries 6 hours after ASCI. The pulmonary alveoli were filled with erythrocytes and serous extravasate 12 hours after ASCI. Hemorrhage and edema were observed in the interstitium and lung alveoli 24 hours after ASCI. CONCLUSIONS: Early pathologic changes such as pulmonary congestion, hemorrhage, and edema after injury may be the basis for early respiratory dysfunction following ASCI. PMID- 26674445 TI - Total disc arthroplasty versus anterior cervical interbody fusion: use of the Spine Tango registry to supplement the evidence from randomized control trials. AB - BACKGROUND CONTEXT: Several randomized controlled trials (RCTs) have compared patient outcomes of anterior (cervical) interbody fusion (AIF) with those of total disc arthroplasty (TDA). Because RCTs have known limitations with regard to their external validity, the comparative effectiveness of the two therapies in daily practice remains unknown. PURPOSE: This study aimed to compare patient reported outcomes after TDA versus AIF based on data from an international spine registry. STUDY DESIGN AND SETTING: A retrospective analysis of registry data was carried out. PATIENT SAMPLE: Inclusion criteria were degenerative disc or disc herniation of the cervical spine treated by single-level TDA or AIF, no previous surgery, and a Core Outcome Measures Index (COMI) completed at baseline and at least 3 months' follow-up. Overall, 987 patients were identified. OUTCOME MEASURES: Neck and arm pain relief and COMI score improvement were the outcome measures. METHODS: Three separate analyses were performed to compare TDA and AIF surgical outcomes: (1) mimicking an RCT setting, with admission criteria typical of those in published RCTs, a 1:1 matched analysis was carried out in 739 patients; (2) an analysis was performed on 248 patients outside the classic RCT spectrum, that is, with one or more typical RCT exclusion criteria; (3) a subgroup analysis of all patients with additional follow-up longer than 2 years (n=149). RESULTS: Matching resulted in 190 pairs with an average follow-up of 17 months that had no residual significant differences for any patient characteristics. Small but statistically significant differences in outcome were observed in favor of TDA, which are potentially clinically relevant. Subgroup analyses of atypical patients and of patients with longer-term follow-up showed no significant differences in outcome between the treatments. CONCLUSIONS: The results of this observational study were in accordance with those of the published RCTs, suggesting substantial pain reduction both after AIF and TDA, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients. PMID- 26674446 TI - The core contribution of transmission electron microscopy to functional nanomaterials engineering. AB - Research on nanomaterials and nanostructured materials is burgeoning because their numerous and versatile applications contribute to solve societal needs in the domain of medicine, energy, environment and STICs. Optimizing their properties requires in-depth analysis of their structural, morphological and chemical features at the nanoscale. In a transmission electron microscope (TEM), combining tomography with electron energy loss spectroscopy and high magnification imaging in high-angle annular dark-field mode provides access to all features of the same object. Today, TEM experiments in three dimensions are paramount to solve tough structural problems associated with nanoscale matter. This approach allowed a thorough morphological description of silica fibers. Moreover, quantitative analysis of the mesoporous network of binary metal oxide prepared by template-assisted spray-drying was performed, and the homogeneity of amino functionalized metal-organic frameworks was assessed. Besides, the morphology and internal structure of metal phosphide nanoparticles was deciphered, providing a milestone for understanding phase segregation at the nanoscale. By extrapolating to larger classes of materials, from soft matter to hard metals and/or ceramics, this approach allows probing small volumes and uncovering materials characteristics and properties at two or three dimensions. Altogether, this feature article aims at providing (nano)materials scientists with a representative set of examples that illustrates the capabilities of modern TEM and tomography, which can be transposed to their own research. PMID- 26674447 TI - Biologically active antimicrobial and antioxidant substances in the Helianthus annuus L. bee pollen. AB - The objective of this study was to measure the content of flavonoids, polyphenols, and carotenoids in the Helianthus annuus L. bee pollen. It was also to evaluate the ability of the dried, frozen, and freeze-dried extracts of sunflower (H. annuus) pollen, its scavenged free radicals and reducing action. Another aim of this study was to investigate the antimicrobial in vitro action of the H. annuus pollen extracts against the Gram-positive and Gram-negative bacteria and fungi. All pollen extracts showed medium antiradical activity and reductive ability. The most effective was the freeze-dried extract in both evaluation systems. The evaluation of the protective effects of DNA using a biosensor showed an opposite trending-frozen ? dried ? freeze-dried pollen. For the evaluation of antiradical activity, the DPPH method was used, and reductive ability was assessed by means of phosphomolybdic complex formation. The comparison of the polyphenols content shows higher values in freeze-dried bee pollen than in the dried and frozen pollen. The highest content of flavonoids was found in the frozen samples and the most carotenoids were present in the dried samples. In our study, the best antibacterial effects of the dried sunflower bee pollen extracts were found against Paenibacillus larvae, Pseudomonas aeruginosa, and Enterococcus raffinosus. The best inhibitory properties of the frozen sunflower bee pollen extracts were found against Escherichia coli, Pseudomonas aeruginosa, and Paenibacillus larvae. Very good inhibitory effects of freeze dried sunflower bee pollen were found against Paenibacillus larvae, Brochotrix thermosphacta, and Enterococcus raffinosus. The best antifungal activity of the sunflower bee pollen was found in the frozen bee pollen extracts against Aspergillus ochraceus and freeze-dried bee pollen extracts against Aspergillus niger. PMID- 26674448 TI - What's New in Shock, January 2016? PMID- 26674449 TI - Comprehensive Interpretation of Central Venous Oxygen Saturation and Blood Lactate Levels During Resuscitation of Patients With Severe Sepsis and Septic Shock in the Emergency Department. AB - OBJECTIVES: We evaluated central venous oxygen saturation (Scvo2) and lactate levels as a combination measure to predict mortality in patients with severe sepsis or septic shock. METHODS: We included patients older than 18 years of age who presented to a single tertiary emergency center with septic shock or severe sepsis and received early goal-directed therapy. We classified the sample into four groups according to lactate (cut-off: 4 mmol/L) and Scvo2 (cut-off: 70%) levels at the time of initial resuscitation: Group 1, high-Scvo2, and low lactate; Group 2, low-Scvo2, and low-lactate; Group 3, high-Scvo2, and high lactate; Group 4, low-Scvo2, and high-lactate. The primary outcome was 28-day mortality determined by multivariable Cox-regression analysis. RESULTS: A total of 880 patients were included in this study. The 28-day mortality was 6.7% in Group 1, 15.7% in Group 2, 26.7% in Group 3, and 25.5% in Group 4 (P < 0.01). Compared with Group 1, all other groups showed significant differences in mortality (P < 0.01 by the log-rank test). There was, however, no difference between Groups 3 and 4. Multivariable Cox regression analysis showed that all other groups exhibited significantly increased hazard ratios for 28-day mortality, compared with Group 1. CONCLUSIONS: Oxygenation category, as represented by initial Scvo2 and lactate levels, was significantly associated with 28-day mortality in patients with severe sepsis or septic shock. Associations between Scvo2 >=70% and 28-day survival were observed only in patients without severe lactic acidosis. PMID- 26674450 TI - Incidence of Sepsis and Mortality With Prior Exposure of HMG-COA Reductase Inhibitors in a Surgical Intensive Care Population. AB - The anti-inflammatory properties of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may reduce the risk of developing sepsis in surgical intensive care patients and improve outcomes in those who do become septic. The objective of this study was to assess whether surgical intensive care unit (SICU) patients with prior exposure to HMG-CoA reductase inhibitors had a lower incidence of developing sepsis and improved outcomes. A retrospective cohort study was conducted. Patient demographic data, statin use, sequential organ failure assessment (SOFA) scores, vasopressor requirements, ventilator days, length of SICU stay, and mortality in septic patients were collected. Incidence of development of sepsis was determined using systemic inflammatory response syndrome criteria. Patients were grouped into cohorts based on whether they met the sepsis criteria and if they had previously received statins. Cohorts of patients who did and did not become septic with prior statin exposure were compared and an odds ratio was calculated to determine a protective effect. The setting was a SICU. The study comprised of 455 SICU patients and had no interventions. Among the 455 SICU patients, 427 patients were included for the final results. Patients receiving statins verses not receiving statins were similar in demographics. Previous statin exposure had a protective effect in the development of sepsis (9.77% on statins vs. 33.6% without statins; odds ratio 0.203, confidence interval 0.118-0.351). Of those patients who developed sepsis, there was a statistically significant decrease in 28-day mortality in patients with prior statin exposure (P = 0.0341). No statistical difference was noted in length of stay, vasopressor requirements, or days on mechanical ventilation. Prior exposure to statins may have a protective effect on the development of sepsis and decrease mortality in critically ill surgical patients. PMID- 26674451 TI - Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients. AB - BACKGROUND: In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. METHODS: Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. RESULTS: Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not differ significantly. CONCLUSIONS: Despite improvements in the management of cirrhotic patients admitted to the ICU and in the management of MV for the treatment of ARDS, cirrhosis remained associated with a poorer prognosis in ARDS patients. The prognosis of cirrhotic patients with ARDS appears related to extrapulmonary organ dysfunctions rather than pulmonary dysfunction. PMID- 26674452 TI - The Role of Lipopolysaccharide Structure in Monocyte Activation and Cytokine Secretion. AB - BACKGROUND: The lipopolysaccharide (LPS) molecule is composed of a hydrophobic lipid region (Lipid A), an oligosaccharide core, and an O-Antigen chain. Lipid A has been described as the molecular region responsible for inducing activation of immune cells. We hypothesize that the O-Antigen plays a critical role in the activation and responsiveness of mononuclear cell immune function. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were stimulated with LPS, LPS with attenuated O-Antigen (RF5), or Lipid A (DPL), which lacks an O-Antigen. Selected cells were pretreated with a blocking antibody to CD14. Western blots were performed to determine activation of mitogen-activated protein kinases (MAPK) p38, ERK, and JNK at selected time-points. RNA was extracted for RT-PCR quantification of TNF-alpha and IL-10 gene transcription. Supernatants were harvested and analyzed by ELISA for tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10). RESULTS: LPS elicited maximal response, including phosphorylation of p38, ERK, and JNK, synthesis of TNF-alpha and IL-10 mRNA, and secretion of TNF-alpha and IL-10. Stimulation with RF5 activated the same pathways to a lesser degree. DPL led to increased phosphorylation of p38 and ERK and increased secretion of IL-10. CD14 blockade was associated with a significant decrease in cytokine secretion by LPS, and abolished cytokine secretion in cells stimulated with RF5 or DPL. CONCLUSIONS: Structural variants of LPS activate monocytes differentially. The complete O-Antigen is important for maximal activation of MAPK, cytokine synthesis, and cytokine secretion. LPS with attenuated O-Antigen and Lipid A activate only certain components of these pathways. LPS with a complete O-Antigen stimulates cytokine secretion that is partially independent of CD14, but shortening or removal of the O-Antigen inhibits this secretion. PMID- 26674453 TI - Enhanced Innate Inflammation Induced by Anti-BTLA Antibody in Dual Insult Model of Hemorrhagic Shock/Sepsis. AB - Sepsis following hemorrhagic shock is a common clinical condition, in which innate immune system suffers from severe suppression. B and T lymphocyte attenuator (BTLA) is an immune-regulatory coinhibitory receptor expressed not only on adaptive, but also on innate immune cells. Our previous data showed that BTLA gene deficient mice were protected from septic mortality when compared with wild-type control C57BL/6 mice. Here, we extended our study by treating C57BL/6 mice with an anti-BTLA monoclonal antibody (clone 6A6; reported to have the ability to neutralize or agonize/potentiate BTLA signaling) in a mouse model of hemorrhagic shock (Hem) followed by sepsis induced by cecal ligation and puncture (CLP); positing initially that if BTLA engagement was neutralized, like gene deficiency, an anti-BTLA mAb would have the similar effects on the inflammatory response/morbidity in these mice after such insults. Here, we report that BTLA expression is elevated on innate immune cells after Hem/CLP. However, anti-BTLA antibody treatment increased cytokine (TNF-alpha, IL-12, IL-10)/chemokine (KC, MIP-2, MCP-1) levels and inflammatory cells (neutrophils, macrophages, dendritic cells) recruitment in the peritoneal cavity, which in turn aggravated organ injury and elevated these animals' mortality in Hem/CLP. When compared with the protective effects of our previous study using BTLA gene deficient mice in a model of lethal septic challenge, we further confirmed BTLA's contribution to enhanced innate cell recruitment, elevated IL-10 levels, and reduced survival, and that engagement of antibody with BTLA potentiates/exacerbates the pathophysiology in Hem/sepsis. PMID- 26674454 TI - Vitamin C Attenuates Hemorrhagic Hypotension Induced Epithelial-Dendritic Cell Transformation in Rat Intestines by Maintaining GSK-3beta Activity and E-Cadherin Expression. AB - OBJECTIVE: To investigate the roles of epithelial-dendritic cell transformation (EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in the occurrence of tissue inflammation induced by hemorrhagic hypotension (HH), the protective effect of vitamin C (VitC), and the potential mechanisms. METHODS: We conducted an in vitro study using the rat intestinal epithelial cells (IEC-6). After hypoxic culture with or without VitC for 2, 6, 24, and 48 h (n = 3 per group), the expression levels of DC-SIGN, E-cadherin, and Glycogen synthase kinase-3beta-S9 (GSK-3beta S9) in IEC-6 cells, IL-1beta, and IL-6 concentrations in the cell culture medium were measured. To investigate the potential mechanism, we inhibited E-cadherin expression by siRNA and GSK-3beta activity by TDZD-8, respectively. The in vivo study was conducted by establishing SD rat HH model. We observed the expression levels and location of DC-SIGN in the intestines. We also showed histological damage, TNF-alpha and IL-6 concentrations, and organ injury scores at 2, 6, and 24 h after HH (n = 6 per group), with or without VitC pretreatment. RESULTS: Hypoxia-induced DC-SIGN expression in IEC-6 cells in a time-dependent manner and the inflammatory factors were also increased. VitC inhibited all these phenomena. Hypoxia inhibited GSK-3beta activity and E-cadherin expression. VitC could ease these inhibitions. The inhibitory effect of VitC on DC-SIGN was diminished when E cadherin expression was inhibited in advance. TDZD-8 diminished the protective effect of VitC on E-cadherin and abolished inhibitory effect of VitC on DC-SIGN expression. HH-induced DC-SIGN expression in rat intestine epithelial cells and the histological damage scores and pro-inflammatory cytokine levels were also increased. CONCLUSIONS: HH induces EDT in rat intestine epithelial cells. VitC maintains GSK-3beta activity, attenuates the suppression of E-cadherin caused by hypoxia, and ultimately decreases DC-SIGN expression. PMID- 26674455 TI - Early Utilization of Extracorporeal CO2 Removal for Treatment of Acute Respiratory Distress Syndrome Due to Smoke Inhalation and Burns in Sheep. AB - INTRODUCTION: In thermally injured patients, inhalation injury is often associated with acute respiratory distress syndrome (ARDS), and is an independent predictor of increased morbidity and mortality. Extracorporeal CO2 removal (ECCO2R) therapy offers new possibilities in protective mechanical ventilation in ARDS patients. We performed an early application of ECCO2R in mild-to-moderate ARDS in sheep ventilated in BiPAP mode. Our aim was to investigate its effect on severity of the lung injury. MATERIAL AND METHODS: Non-pregnant farm-bred ewes (n = 15) were anesthetized and injured by a combination of wood-bark smoke inhalation and a 40% total body surface area full-thickness burn, and were observed for 72 h or death. The animals were randomized to a Hemolung group (n = 7) or a Control group (n = 8) at time of ARDS onset. ECCO2R was performed in the Hemolung group after onset of ARDS.Histopathology, CT scans, systemic and pulmonary variables, and CO2 removal were examined. RESULTS: Early application of ECCO2R therapy with Hemolung in spontaneously breathing sheep decreased PaCO2 significantly, while the device removed about 70 mL of CO2 per minute. This did not result in lower minute ventilation in the Hemolung group. Lungpathology and CT scans did not show a difference between groups. CONCLUSION: In an ovine model of ARDS due to smoke inhalation and burn injury, early institution of ECCO2R in spontaneously breathing animals was effective in removing CO2 and in reducing PaCO2. However, it had no effect on reducing the severity of lung injury or mortality. Further studies are necessary to detail the interaction between extracorporeal CO2 removal and pulmonary physiology. PMID- 26674456 TI - Effect of External Pressure and Catheter Gauge on Flow Rate, Kinetic Energy, and Endothelial Injury During Intravenous Fluid Administration in a Rabbit Model. AB - The effects of intravenous (IV) catheter gauge and pressurization of IV fluid (IVF) bags on fluid flow rate have been studied. However, the pressure needed to achieve a flow rate equivalent to that of a 16 gauge (G) catheter through smaller G catheters and the potential for endothelial damage from the increased kinetic energy produced by higher pressurization are unclear. Constant pressure on an IVF bag was maintained by an automatic adjustable pneumatic pressure regulator of our own design. Fluids running through 16 G, 18 G, 20 G, and 22 G catheters were assessed while using IV bag pressurization to achieve the flow rate equivalent to that of a 16 G catheter. We assessed flow rates, kinetic energy, and flow injury to rabbit inferior vena cava endothelium. By applying sufficient external constant pressure to an IVF bag, all fluids could be run through smaller (G) catheters at the flow rate in a 16 G catheter. However, the kinetic energy increased significantly as the catheter G increased. Damage to the venous endothelium was negligible or minimal/patchy cell loss. We designed a new rapid infusion system, which provides a constant pressure that compresses the fluid volume until it is free from visible residual fluid. When large-bore venous access cannot be obtained, multiple smaller catheters, external pressure, or both should be considered. However, caution should be exercised when fluid pressurized to reach a flow rate equivalent to that in a 16 G catheter is run through a smaller G catheter because of the profound increase in kinetic energy that can lead to venous endothelium injury. PMID- 26674457 TI - 1,1,2,2-Tetracyanocyclopropane (TCCP) as supramolecular synthon. AB - The 1,1,2,2-tetracyanocyclopropane (TCCP) unit presents a synthetically accessible and versatile synthon that can interact with lone-pair or pi-electrons by 'non-covalent carbon bonding'. Complexes of TCCP with common small molecules, anions, aromatics like fullerenes, amino acids and nucleobases were computed at the DFT BP86-D3/def2-TZVP level of theory. Binding energies vary between about 10 kcal mol(-1) for neutral guests and -15 to -50 kcal mol(-1) for anionic species. This is comparable to strong and very strong hydrogen bonding respectively. Thus, in addition to synthons that contain polarized hydrogen or halogen atoms, TCCP presents a new supramolecular synthon that awaits experimental exploitation. PMID- 26674458 TI - Self-organization of dislocation-free, high-density, vertically aligned GaN nanocolumns involving InGaN quantum wells on graphene/SiO2 covered with a thin AlN buffer layer. AB - We demonstrated the self-organization of high-density GaN nanocolumns on multilayer graphene (MLG)/SiO2 covered with a thin AlN buffer layer by RF-plasma assisted molecular beam epitaxy. MLG/SiO2 substrates were prepared by the transfer of CVD graphene onto thermally oxidized SiO2/Si [100] substrates. Employing the MLG with an AlN buffer layer enabled the self-organization of high density and vertically aligned nanocolumns. Transmission electron microscopy observation revealed that no threading dislocations, stacking faults, or twinning defects were included in the self-organized nanocolumns. The photoluminescence (PL) peak intensities of the self-organized GaN nanocolumns were 2.0-2.6 times higher than those of a GaN substrate grown by hydride vapor phase epitaxy. Moreover, no yellow luminescence or ZB-phase GaN emission was observed from the nanocolumns. An InGaN/GaN MQW and p-type GaN were integrated into GaN nanocolumns grown on MLG, displaying a single-peak PL emission at a wavelength of 533 nm. Thus, high-density nitride p-i-n nanocolumns were fabricated on SiO2/Si using the transferred MLG interlayer, indicating the possibility of developing visible nanocolumn LEDs on graphene/SiO2. PMID- 26674459 TI - Locoregional Therapy for Hepatocellular Carcinoma. PMID- 26674460 TI - Standards of the Polish Ultrasound Society. Ultrasound examination in anesthesiology and intensive care. AB - This article has been prepared on the basis of the Ultrasonography Standards of the Polish Ultrasound Society (2011) and updated based on the latest findings and reports. Various applications of ultrasonography are used in anesthesiology and intensive therapy both for diagnosis and as a supportive tool during invasive procedures (such as vascular cannulation or regional anesthesia). Ultrasound examinations performed by anesthesiologists in intensive care units are not detailed scans, but they are focused on immediate identification of pathologies that lead to life-threatening conditions. Performing repeated US exams in time intervals enables a physician to monitor the effectiveness of the instituted treatment. Many simplified protocols are used in clinical practice which help to systemize the examination. Focused US examination should be verified by a physician competent in this imaging method as soon as possible. Due to the specificity of anesthesiologists' practice and spatial limitations of operating rooms and intensive care units, portable robust ultrasound equipment with short power-on to scanning time is preferable. A growing number of indications show that ultrasound machine should be equipped with three basic transducers (linear, convex and sector), and in higher-reference centers with a transesophageal probe. The specificity of certain procedures guided by ultrasonography requires adherence to safety measures, e.g. full sterility condition during vein cannulation. PMID- 26674461 TI - Conversion of the helical tomotherapy plans to the step-and-shoot IMRT plans for patients with hip prosthesis during radiotherapy for prostate cancer. AB - PURPOSE: To evaluate the SharePlan software in conversion of helical tomotherapy (HT) to a step and shoot IMRT (sIMRT) for patients with high-risk prostate cancer and hip prosthesis. METHODS: Analysis was performed for 16 consecutive patients treated on HT. The HT plans were converted to sIMRT plans. 3DCRT, sliding window IMRT (dIMRT) and VMAT plans for a c-arm linear accelerator (CLA) were created manually. The doses in planning target volume (PTV), bladder, rectum, bowels, femoral heads and hip prosthesis were compared using: (i) a qualitative analysis of doses in averaged dose-volume histograms, (ii) a quantitative, ranking procedure performed for each patient separately, and (iii) statistical testing based on the Friedman ANOVA and Nemenyi method. RESULTS: For the bladder, rectum, and femoral head, the best dose distributions were observed for HT and sIMRT and then for dIMRT, VMAT, and finally for 3DCRT (p-values were, respectively, 0.002, 0.004 and p = 0.024). For the bowels, 3DCRT was significantly different from the rest of the techniques (p = 0.009). For the hip prosthesis, the differences were only between 3DCRT and HT/sIMRT (p = 0.038). CONCLUSION: The SharePlan is an efficient tool for the conversion of HT plans for patients with prostate cancer and hip prosthesis. Dose distributions in sIMRT and in HT plans are similar and are generally better than in CLA plans. PMID- 26674462 TI - 3D imaging options and ultrasound contrast agents for the ultrasound assessment of pediatric rheumatic patients. AB - The application of 3D imaging in pediatric rheumatology helps to make the assessment of inflammatory changes more objective and to estimate accurately their volume and the actual response to treatment in the course of follow-up examinations. Additional interesting opportunities are opened up by the vascularity analysis with the help of power Doppler and color Doppler in 3D imaging. Contrast-enhanced ultrasound examinations enable a more sensitive assessment of the vascularity of inflamed structures of the locomotor system, and a more accurate analysis of treatment's effect on changes in vascularity, and thereby the inflammation process activity, as compared to the classical options of power and color Doppler. The equipment required, time limitations, as well as the high price in the case of contrast-enhanced ultrasound, contribute to the fact that the 3D analysis of inflammatory changes and contrast-enhanced ultrasound examinations are not routinely applied for pediatric patients. PMID- 26674463 TI - Acute intravenous glucose load impairs early insulin secretion and insulin content in islet beta cells in mice. AB - AIMS: To investigate insulin secretion and content in islet beta cells after intravenous glucose load in mice. MATERIALS AND METHODS: Acute hyperglycemia (>=16.7 mmol/L) in C57BL/J6 mice was achieved by hyperglycemic clamp. Mice were divided into four groups: a 2-hour and a 4-hour high glucose-infusion (2 h-HG and 4 h-HG) with 25% dextrose groups and control groups with saline infusion of the same duration. Insulin levels and response were measured using intraperitoneal glucose tolerance test (IPGTT) in mice and glucose-stimulated insulin secretion (GSIS) for isolated islets after overnight culture. Immunohistochemistry and electron microscopy (EM) for islet beta cells were used after the hyperglycemic clamp to study morphologic changes of insulin granules and to assess the impact of acute glucose load on islet histology. KEY FINDINGS: Blood glucose at 15, 30, 60 and 120 min was significantly higher in 4 h-HG compared with the other groups. Serum plasma insulin significantly decreased only at 15 min as a first-phase insulin response (FPIR). Insulin secretion at 2.8 and 16.7 mmol/L glucose stimulus in 4 h-HG group decreased 77% and 64% more than those in 2 h-HG, respectively (P<0.05). Similarly, residual insulin content in islet beta cells after 2.8 and 16.7 mmol/L glucose challenge decreased 30% and 43% more than those in 2 h-HG, respectively (P<0.05). EM showed decreased insulin granules in islet cells and swollen mitochondria only in 4 h-HG. SIGNIFICANCE: Short time intravenous glucose load blunted FPIRs and decreased insulin content of islet beta cells. PMID- 26674464 TI - Decreased reactive oxygen species production and NOX1, NOX2, NOX4 expressions contribute to hyporeactivity to phenylephrine in aortas of pregnant SHR. AB - AIMS: We determined whether decreased reactive oxygen species (ROS) production in the aorta of pregnant spontaneously hypertensive rats (SHR) resulted in increased nitric oxide (NO) bioavailability and hyporeactivity to phenylephrine (PE). MAIN METHODS: Systemic and aortic oxidative stress were measured in pregnant and non pregnant Wistar rats and SHR. Furthermore, the hypotensive effects of apocynin (30 mg/kg) and Tempol (30 mg/kg) were analyzed. Intact aortic rings of pregnant and non-pregnant rats were stimulated with PE in the absence of or after incubation (30 min) with apocynin (100 MUmol/L). The effect of apocynin on the concentrations of NO and ROS were measured in aortic endothelial cells (AEC) using DAF-2DA (10 mmol/L) and DHE (2.5 mmol/L), respectively. Western blotting was performed to analyze eNOS, NOX1, NOX2, NOX4 and SOD expression. ROS production was analyzed by the lucigenin chemiluminescence method. KEY FINDINGS: Aortic oxidative stress and ROS concentration in AEC were reduced in pregnant Wistar rats and SHR, when compared to non-pregnant rats. ROS production and NOX1, NOX2 and NOX4 expression in the aortas were decreased in pregnant SHR, but not in pregnant Wistar rats. Increased eNOS expression in aortas and NO concentration in AEC were observed in pregnant Wistar rats and SHR. Apocynin reduced PE-induced vasoconstriction in the aortas of non-pregnant Wistar rats and SHR, and pregnant Wistar rats, but not in the aortas of pregnant SHR. SIGNIFICANCE: Taken together, these results suggest that ROS production was decreased in the aortas of pregnant SHR and could contribute to higher NO bioavailability and hyporeactivity to PE in the aortas of pregnant SHR. PMID- 26674465 TI - Adaptation of the Psychological-Behavioral Acculturation Scale to a Community of Urban-based Mexican Americans in the United States. AB - OBJECTIVE: To report the psychometric properties of the Psychological-Behavioral Acculturation Scale (P-BAS), a tool gauging behavioral and psychological acculturation after adapting it through formative research to people of Mexican origin in the United States. METHODS: We analyzed data from adapted P-BAS questionnaires in the TalaSurvey study, using standard methods to establish internal consistencies (Cronbach's alpha), construct validity, and ascertain if the value orientation profile differed by ethnic group. RESULTS: In 2012-13, 505 respondents (mean age 45.2 +/- 14.1, 56% female) participated: 250 European Americans (EA) and 255 people of Mexican origin (MA). CONCLUSIONS: Although internal consistencies of 15 value orientation measures were occasionally low, overall results were encouraging. A weighted combination of value orientation scores strongly discriminated between EA and MA. Additionally, the pattern of relationships among MAs identified between acculturation scores and the validity contrasts supported the construct validity of the proposed dual framework. The trend was particularly evident for most behavioral variables. PMID- 26674466 TI - Treatment Resistant Hypertension. AB - Treatment resistant hypertension (TRH) is defined by office blood pressure (BP) uncontrolled on >= 3 or controlled on >= 4 antihypertensive medications, preferably at optimal doses and including a diuretic. Apparent (a)TRH is used when optimal therapy, adherence, and measurement artifacts are unknown. Among treated hypertensives, ~30% of uncontrolled and 10% of controlled individuals have aTRH, with a higher prevalence in Blacks than other race-ethnicity groups. In >= 50% of aTRH patients, BP measurement artifacts ('office' TRH), suboptimal regimens, or suboptimal adherence are present, ie, pseudo-resistance. While patients with 'office' TRH have fewer cardiovascular events than those with 'true' TRH, no evidence confirms that patients with suboptimal regimens or adherence are spared. Averaging several office BPs obtained with an automated monitor can reduce 'office' TRH. Home or ambulatory BP monitoring can identify office resistance. Prescribing >= 3 different antihypertensive medication classes, eg, thiazide-type diuretic, renin-angiotensin blocker and calcium antagonist at >= 50% of maximum recommended doses reasonably defines optimal therapy. Intensifying diuretic therapy, eg, adding an aldosterone antagonist, is effective for many TRH patients who are volume expanded. Clinical information, hemodynamic and renin-guided therapeutics can inform other treatment options. Attention to adverse effects, medication costs, and pill burden can improve adherence and control. Patients with aTRH and suspected secondary hypertension should be evaluated. Interfering substances or medications should be discontinued. These approaches will identify or correct the problem in ~80% of aTRH patients. Referral to a hypertension specialist and newer therapeutic approaches are options for TRH patients who cannot take or do not respond to optimal therapy. PMID- 26674467 TI - Ultrasound assessment of the jugular and vertebral veins in healthy individuals: selected physiological aspects and morphological parameters. AB - AIM: Ultrasound assessment of morphological parameters of the internal jugular veins and vertebral veins in healthy individuals as well as their dependence on the patient's position. MATERIAL: The examinations were conducted in 185 healthy individuals (101 females and 84 males) aged 18-89. Ultrasound examinations were conducted with the use of a linear probe with the frequency of 5-9 MHz in the supine (0 degrees ) and sitting position (90 degrees ). RESULTS: In 154 cases (83.2%) on the left side and in 150 cases (81.1%) on the right side, the jugular veins were completely closed in the sitting position. In 31 cases (16.8%) on the left side and in 35 cases (18.9%) on the right side, they were merely narrowed. By contrast with the jugular veins, the cross-sectional area (CSA) of the vertebral veins was greater in the sitting position than in the supine position in a statistically significant way. The CSA values of the jugular veins in the supine position ranged from 0 cm(2) to 4.3 cm(2). There were no statistically significant differences in the CSA between men and women. The cross-sectional area of the right jugular vein in the supine position was greater in a statistically significant way than that of the left jugular vein. In this study population, the ratio of the cross-sectional areas of the jugular veins on both sides amounted to 8.5:1. CONCLUSIONS: The width of the jugular and vertebral veins significantly varies depending on the patient's position. The range of the CSA values for the jugular veins is broad, which should be taken into account when interpreting imaging findings. The internal jugular veins can show considerable asymmetry. PMID- 26674468 TI - Prenatal undernutrition results in greater lipopolysaccharide-induced changes in hypothalamic TNF-alpha expression, but does not affect the equivalent changes in the serum levels of luteinizing hormone and testosterone, in adult male rats. AB - Immune stress can cause reproductive dysfunction. Some hypothalamic factors such as pro-inflammatory cytokines play pivotal roles in reproductive disorders under immune stress conditions. Recently, it has been reported that prenatal undernutrition affects not only metabolic functions, but also the responses of physiological functions to immune stress in adulthood. In this study, the long term effects of prenatal undernutrition on the responses of hypothalamic pro inflammatory cytokine (interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6) expression; reproductive endocrine factors; i.e., the serum levels of gonadotropins and testosterone; and hypothalamic kisspeptin expression to lipopolysaccharide (LPS) were examined in male rats. Pregnant rats were divided into two groups; i.e., the normally nourished group and the undernourished (50% food restricted) group. The offspring of the normally nourished mothers (control) and undernourished mothers (the intrauterine growth restriction [IUGR] group) were sub-divided into saline-injected and LPS (500 MUg, i.p.)-injected groups at 10 weeks of age. The rats' hypothalamic pro-inflammatory cytokine levels and serum luteinizing hormone (LH) and testosterone levels were measured and compared between the control and IUGR groups. The hypothalamic pro-inflammatory cytokine mRNA levels of the LPS-injected rats were significantly higher than those of the saline-injected rats in both the control and IUGR groups. The changes in the hypothalamic expression level of TNF-alpha, but not those of the other cytokines, induced in response to LPS were more marked in the IUGR group than in the control group. On the other hand, although the serum LH and testosterone levels of the LPS-injected rats were significantly lower than those of the saline-injected rats in both the control and IUGR groups, their levels did not differ between the control and IUGR groups under the LPS-injected conditions. These results suggest that prenatal undernutrition results in more marked LPS-induced changes in hypothalamic TNF-alpha expression, but does not alter the effects of LPS on the serum levels of LH or testosterone, in adult male rats. PMID- 26674469 TI - Cribriform carcinoma mimicking breast abscess - case report. Diagnostic and therapeutic management. AB - The authors presents a case of cribriform breast carcinoma in a cyst that clinically imitated an abscess. The case concerns a 71-year-old female patient treated for ankylosing spondylitis, with a positive family history of breast cancer. The patient presented at the surgical clinic for incision of an abscess of the mammary gland localized in the lower inner quadrant that was a consequence of previous trauma to the right breast. The abscess was incised and the serosanguineous contents were evacuated. The wound was drained and antibiotics (Dalacin with Metronidazol) were administered for the period of 10 days. During the treatment, a cutaneous fistula was formed. At the incision site, a hard thickening was palpable (tumor). Core needle biopsy of the clinically palpable tumor was performed and the purulent material from the fistula was collected for a culture test. Complete blood count did not reveal leucocytosis. In accordance with the obtained sensitivity report, the patient was started on antibiotics again. Breast ultrasound performed upon the completion of the antibiotic therapy, in the right breast, revealed two solidcystic oval lesions with thick echogenic walls and blurred margins. Both masses contained dense levels of fluid material and solid polycyclic structures. On sonoelastography, the lesions were heterogeneous with a high Young's modulus. In the right axillary fossa, ultrasound examination revealed three abnormal lymph nodes enlarged to 31 mm length, which were rounded, hypoechoic and without visible sinuses. Histopathology of the core needle biopsy performed at admittance and after the antibiotic therapy indicated a breast abscess (presence of fibrinous and partly fibrinopurulent material). The mass was finally resected to confirm histopathology. The resected material revealed the presence of an invasive, moderately differentiated cribriform carcinoma, which developed within a cyst, with a 40% necrotic component. Eighteen months after the commencement of treatment, the patient remains under oncological supervision and continues hormonal therapy. There are no signs of relapse or foci of distant metastases. The occurrence of breast carcinoma within an abscess emphasises the need for comprehensive assessment and correlation of the clinical picture with imaging and histopathological findings. It also highlights the necessity to include breast abscess in the differential diagnosis of rare forms of carcinomas. PMID- 26674470 TI - Efflux pump induction by quaternary ammonium compounds and fluoroquinolone resistance in bacteria. AB - Biocides, primarily those containing quaternary ammonium compounds (QAC), are heavily used in hospital environments and various industries (e.g., food, water, cosmetic). To date, little attention has been paid to potential implications of QAC use in the emergence of antibiotic resistance, especially fluoroquinolone resistant bacteria in patients and in the environment. QAC-induced overexpression of efflux pumps can lead to: cross resistance with fluoroquinolones mediated by multidrug efflux pumps; stress response facilitating mutation in the Quinolone Resistance Determining Region; and biofilm formation increasing the risk of transfer of mobile genetic elements carrying fluoroquinolone or QAC resistance determinants. By following the European Biocidal Product Regulation, manufacturers of QAC are required to ensure that their QAC-based biocidal products are safe and will not contribute to emerging bacterial resistance. PMID- 26674471 TI - Biological inflammatory markers mediate the effect of preoperative pain-related behaviours on postoperative analgesics requirements. AB - BACKGROUND: The predictive value of an individual's attitude towards painful situations and the status of his immune system for postoperative analgesic requirements are not well understood. These may help the clinician to anticipate individual patient's needs. METHODS: Sixty patients, who underwent a laparoscopic cholecystectomy under standardised general anaesthesia, were included. The total analgesic requirements during the first 48 h were the primary endpoint (unitary dosage, UD). The individual's attitude towards imaginary painful situations was measured with the Situational Pain Scale (SPS). The emotional status was assessed by the Hospital Anxiety and Depression Scale (HADS) and the inflammatory status by the neutrophil-to-lymphocyte ratio (NLR). RESULTS: Univariate analyses revealed a significant association between UD and SPS, HADS and NLR. A negative relationship between SPS and NLR (NLR = 0.820-0.180*SPS;R(2) = 0.211;P < 0.001) and a positive relationship between SPS and HADS (HADS = 14.8 + 1.63*SPS; R(2) = 0.159;P = 0.002) were observed. A multiple linear regression analysis showed that the contribution of NLR to the UD was the most effective. A mediation analysis showed a complete mediation of the effect of SPS on UD (R(2) = 0.103;P = 0.012), by the NLR (SPS on NLR: R(2) = 0.211;P = <0.001), the HADS (SPS on HADS: R(2) = 0.159;P = 0.002). The variance in UD explained by the SPS was indirect and amounts to 46% through NLR and to 34% through HADS. CONCLUSIONS: In this series, preoperative pain-related attitudes (SPS) were associated with the postoperative analgesic requirements (UD) after a cholecystectomy. Eighty per cent of this effect was mediated by the HADS and the NLR. PMID- 26674472 TI - Effects of wild type tau and disease-linked tau mutations on microtubule organization and intracellular trafficking. AB - We investigate the effects of transient expression of wild type (WT) and disease linked mutations of tau (R406W, P301L, DeltaN296) on cytoskeletal organization and cargo transport in COS-7 cells, which are natively tau-free. The introduction of tau proteins (either WT or mutant forms) leads to a dramatic restructuring of the microtubule cytoskeleton, as observed using immunofluorescence microscopy. Yet, this microtubule bundling and aggregation has a modest effect on the speed and travel distance of motor-driven cargo transport, as measured by the motions of fluorescently-labeled lysosomes. This suggests that localized transport events are insensitive to the global structure of the microtubule cytoskeleton. Importantly, we also found no evidence that the disease-linked tau mutants were particularly toxic; in fact we found that expression of mutant and WT tau had similar effects on overall microtubule structure and transport phenotypes. PMID- 26674473 TI - Lateral migration of a capsule in a parabolic flow. AB - Red blood cells migrate to the center of the blood vessel in a process called axial migration, while other blood cells, such as white blood cells and platelets, are disproportionately found near the blood vessel wall. However, much is still unknown concerning the lateral migration of cells in the blood; the specific effect of hydrodynamic factors such as a wall or a shear gradient is still unclear. In this study, we investigate the lateral migration of a capsule using the boundary integral method, in order to compute exactly an infinite computational domain for an unbounded parabolic flow and a semi-infinite computational domain for a near-wall parabolic flow in the limit of Stokes flow. We show that the capsule lift velocity in an unbounded parabolic flow is linear with respect to the shear gradient, while the lift velocity in a near-wall parabolic flow is dependent on the distance to the wall. Then, using these relations, we give an estimation of the relative effect of the shear gradient as a function of channel width and distance between the capsule and the wall. This estimation can be used to determine cases in which the effect of the shear gradient or wall can be neglected; for example, the formation of the cell-free layer in blood vessels is determined to be unaffected by the magnitude of the shear gradient. PMID- 26674474 TI - High-dose vitamin D supplementation does not alter bone mass or muscle function over 1 year in postmenopausal women. PMID- 26674476 TI - A double decker type complex: copper(i) iodide complexation with mixed donor macrocycles via [1 : 1] and [2 : 2] cyclisations. AB - 19-membered and a 38-membered macrocycles obtained as a mixture via respective [1 : 1] and [2 : 2] cyclisations were separated and their coordination behaviours with copper(i) iodide were investigated. One of the notable products isolated is a tetranuclear bis(macrocycle) complex with the larger macrocycle adopting a double decker type structure. Furthermore, removal of the lattice solvent molecules in the above complex in air motivates the displacement of the double decker units along the a-axis by sliding in a single-crystal-to-single-crystal manner. PMID- 26674475 TI - Synthesis and Self-Assembly of Bundle-Forming alpha-Helical Peptide-Dendron Hybrids. AB - Dendronized helix bundle assemblies combine the sequence diversity and folding properties of proteins with the tailored physical properties of dendrimers. Assembly of peptide-dendron hybrids into alpha-helical bundles encapsulates the helix bundle motif in a dendritic sheath that will allow the functional, protein like domain to be transplanted to nonbiological environments. A bioorthogonal graft-to synthetic strategy for preparing helix bundle-forming peptide-dendron hybrids is described herein for hybrids 1a, 1b, and 2. Titration experiments monitored by circular dichroism spectroscopy support our self-assembly model for how the peptide-dendron hybrids self-assemble into alpha-helical bundles with the dendrons on outside of the bundle. PMID- 26674477 TI - A comparison of the bioactivity and phytochemical profile of three different cultivars of globe amaranth: red, white, and pink. AB - The phytochemical profiles and bioactivities of red, white and pink globe amaranth (Gomphrena haageana K., Gomphrena globosa var. albiflora and Gomphrena sp., respectively), much less studied than the purple species (G. globosa L.), were compared. The chemical characterization of the samples included the analysis of macronutrients and individual profiles of sugars, organic acids, fatty acids, tocopherols, and phenolic compounds. Their bioactivity was evaluated by determining the antioxidant and anti-inflammatory activities; the absence of cytotoxicity was also determined. Red and pink samples showed the highest sugar content. Otherwise, the white sample gave the highest level of organic acids, and together with the pink one showed the highest tocopherol and PUFA levels. Quercetin-3-O-rutinoside was the major flavonol in white and pink samples, whereas a tetrahydroxy-methylenedioxyflavone was the major compound in the red variety, which revealed a different phenolic profile. The pink globe amaranth hydromethanolic extract revealed the highest antioxidant activity, followed by those of red and white samples. The anti-inflammatory activity was more relevant in red and pink varieties. None of the samples presented toxicity in liver cells. Overall, these samples can be used in bioactive formulations against inflammatory processes and in free radical production. PMID- 26674479 TI - Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review. AB - BACKGROUND: Delirium is the most often encountered psychiatric diagnosis in the general hospital, with an incidence of up to 82% in the intensive care unit setting and with significant detrimental effects on patients' morbidity and mortality. Antipsychotics are often considered the first-line pharmacological treatment of delirium, but their use may be limited by lack of efficacy, existing contraindications (e.g., prolonged QTc intervals), or resulting side effects (e.g., akathisia). Valproic acid (VPA) is a potential alternative or adjunct treatment. It has multiple mechanisms of action, including effects on neurotransmitter modulation, neuroinflammation, oxidative stress, and transcription, all of which are implicated in the pathophysiology of delirium. Yet, data on the use of this agent in delirium are limited. OBJECTIVE/METHODS: In this article, we discuss postulated mechanisms of VPA action that provide a theoretical basis for its use in the treatment of hyperactive and mixed type delirium, based on the known and theorized pathophysiology of delirium. We also discuss potential side effects and considerations with use of VPA. CONCLUSIONS: VPA has multiple modulatory effects on neurotransmitter systems, inflammation, oxidative stress, and transcriptional changes implicated in pathophysiology of delirium. When carefully chosen, VPA can be an effective and well-tolerated treatment option for the management of hyperactive and mixed type delirium. Randomized controlled trials are needed to establish tolerability and efficacy of VPA for treatment of delirium. PMID- 26674480 TI - Memorial Minute. PMID- 26674481 TI - Memorial Minute. PMID- 26674478 TI - The emerging role of Slit-Robo pathway in gastric and other gastro intestinal cancers. AB - Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Due to the high frequency of metastasis, it is still one of the most lethal malignancies in which kinds of signaling pathways are involved in. The Roundabout (ROBO) receptors and their secreted SLIT glycoprotein ligands, which were originally identified as important axon guidance molecules, have implication in the regulation of neurons and glia, leukocytes, and endothelial cells migration. Recent researches also put high emphasis on the important roles of the Slit-Robo pathway in tumorigenesis, cancer progression and metastasis. Herein we provide a comprehensive review on the role of these molecules and their associated signaling pathway in gastric and other gastrointestinal cancers. Improved knowledge of the Slit-Robo signaling pathway in gastric carcinoma will be useful for deep understanding the mechanisms of tumor development and identifying ideal targets of anticancer therapy in gastric carcinoma. PMID- 26674482 TI - The Roots of Psychosomatic Medicine II: George L. Engel. AB - OBJECTIVE: The purpose of this article is to examine and appreciate the contributions of George Libman Engel, MD, to psychosomatic medicine. CONCLUSION: Engel was a prolific researcher, medical educator, and writer who championed the biopsychosocial model, which has been widely embraced and practiced in psychiatry and medicine to this day. In the late 1970s, when Engel published his seminal article on the biopsychosocial model, the dominant model of medicine was still the biomedical model. This model considered the most important and scientifically sound aspects of patient history to be those that could be easily quantified, such as laboratory values. The biomedical model left no room for the psychosocial aspects, such as the patient's relationships and social status, to be integrated into patient care. Though many had expressed dissatisfaction with the biomedical model and suspected that it was too 1 dimensional to provide adequate patient care, Engel was among the first to propose a replacement model. Furthermore, he stipulated that there is a scientific necessity to consider psychosocial aspects of patient history to provide the most complete diagnoses and treatment plan. Along with his biopsychosocial approach to the patient, Engel also contributed heavily to research and to education of medical students. His legacy is one of compassionate, scientific doctoring. PMID- 26674483 TI - The Early-Career Consultation Psychiatrist: Leading the Integration of Substance Use Treatment Into the Primary Care Setting. PMID- 26674484 TI - Suspected Secondhand Smoke and Clozapine Toxicity. PMID- 26674485 TI - Intracerebral Bullet Fragments: Toxic or Concussive Effect? PMID- 26674486 TI - Barriers beyond clinical control affecting timely hospital discharge for a patient requiring guardianship. PMID- 26674487 TI - Rilpivirine and Depression. PMID- 26674488 TI - Capacity Evaluations in Late-Stage Pregnancy. PMID- 26674489 TI - Synthetic Cannabis and Myocardial Infarction: A Complication Less Known! PMID- 26674490 TI - Polycistronic transcription of fused cassettes and identification of translation initiation signals in an unusual gene cassette array from Pseudomonas aeruginosa. AB - The gene cassettes found in class 1 integrons are generally promoterless units composed by an open reading frame (ORF), a short 5' untranslated region (UTR) and a 3' recombination site ( attC). Fused gene cassettes are generated by partial or total loss of the attC from the first cassette in an array, creating, in some cases, a fusion with the ORF from the next cassette. These structures are rare and little is known about their mechanisms of mobilization and expression. The aim of this study was to evaluate the dynamic of mobilization and transcription of the gcu14-bla GES-1 /aacA4 gene cassette array, which harbours a fused gene cassette represented by bla GES-1 /aacA4. The cassette array was analyzed by Northern blot and real-time reverse transcription-polymerase chain reaction (RT PCR) in order to assess the transcription mechanism of bla GES-1 /aacA4 fused cassette. Also, inverse polymerase chain reactions (PCR) were performed to detect the free circular forms of gcu14, bla GES-1 and aacA4. The Northern blot and real time RT-PCR revealed a polycistronic transcription, in which the fused cassette bla GES-1 /aacA4 is transcribed as a unique gene, while gcu14 (with a canonical attC recombination site) has a monocistronic transcription. The gcu14 cassette, closer to the weak configuration of cassette promoter (PcW), had a higher transcription level than bla GES-1/ aacA4, indicating that the cassette position affects the transcript amounts. The presence of ORF-11 at attI1, immediately preceding gcu14, and of a Shine-Dalgarno sequence upstream bla GES-1/ aacA4 composes a scenario for the occurrence of array translation. Inverse PCR generated amplicons corresponding to gcu14, gcu14-aacA4 and gcu14-bla GES-1/ aacA4 free circular forms, but not to bla GES-1 and aacA4 alone, indicating that the GES-1 truncated attC is not substrate of integrase activity and that these genes are mobilized together as a unique cassette. This study was original in showing the transcription of fused cassettes and in correlating cassette position with transcription. PMID- 26674491 TI - The association of mobility disability, weight status and job strain: A cross sectional study. AB - AIMS: The study investigated whether people with mobility disability (MD) and/or obesity had higher job strain than people without it, and whether social support at work modifies this association. METHODS: The study included 35,160 individuals (25-64 years of age) from the Stockholm Public Health Surveys of 2006 and 2010. Data on MD and obesity (BMI ? 30 kg/m(2)calculated from weight (kg) and height (m)) were self-reported. According to the Demand-Control-Support theory job strain, collective strain, and isolated strain were calculated for six groups of people based on the presence of MD and obesity, using the subtraction approach (demand minus control). Differences in job strain mean scores were estimated by multivariate linear regression. Social support at work was analyzed as a potential effect modifier (high/low). RESULTS: Obese people with MD had the highest job strain (beta = 0.92, 95% CI 0.64-1.19), compared to normal weight people without MD (reference group). We found that social support at work significantly (p<0.001) modifies the association between job strain, MD and obesity. Obese people with MD had the highest isolated strain (beta = 2.92, 95% CI 2.52-3.31), and the highest collective strain, although of smaller magnitude (beta = 0.34, 95% CI 0.05-0.63), compared to the reference group. CONCLUSIONS: Obese people with MD perceive higher job strain than non-disabled people of normal weight. Strategies aiming to increase the social support at work may be important for this group of people to prevent them from experiencing unhealthy job strain. PMID- 26674492 TI - Screening of a healthy newborn identifies three adult family members with symptomatic glutaric aciduria type I. AB - We report three adult sibs (one female, two males) with symptomatic glutaric acidura type I, who were diagnosed after a low carnitine level was found by newborn screening in a healthy newborn of the women. All three adults had low plasma carnitine, elevated glutaric acid levels and pronounced 3-hydroxyglutaric aciduria. The diagnosis was confirmed by undetectable glutaryl-CoA dehydrogenase activity in lymphocytes and two pathogenic heterozygous mutations in the GCDH gene (c.1060A > G, c.1154C > T). These results reinforce the notion that abnormal metabolite levels in newborns may lead to the diagnosis of adult metabolic disease in the mother and potentially other family members. PMID- 26674494 TI - Cost-effectiveness of a cardiac output-guided haemodynamic therapy algorithm in high-risk patients undergoing major gastrointestinal surgery. AB - BACKGROUND: The use of cardiac output monitoring to guide intra-venous fluid and inotropic therapies may improve peri-operative outcomes, but uncertainty exists regarding clinical effectiveness and robust cost-effectiveness evidence is lacking. The objective of the study was to evaluate the cost-effectiveness of peri-operative cardiac output-guided haemodynamic therapy versus usual care in high-risk patients undergoing major gastrointestinal surgery. METHODS: The study undertook a cost-effectiveness analysis using data from a multi-centre randomised trial that recruited patients from 17 hospitals in the United Kingdom. The trial compared cardiac output-guided, haemodynamic therapy algorithm for intra-venous fluid and inotrope (dopexamine) infusion during and 6 h following surgery, with usual care. Resource use and outcome data on 734 high-risk trial patients aged over 50 years undergoing major gastrointestinal surgery were used to report cost effectiveness at 6 months and to project lifetime cost-effectiveness. The cost effectiveness analysis used information on health-related quality of life (QoL) at randomisation, 30 days, and 6 months combined with information on vital status to report quality-adjusted life years (QALYs). Each QALY was valued using the National Institute for Health and Care Excellence (NICE) recommended threshold of willingness to pay (L20,000 per QALY) in conjunction with the costs of each group to report the incremental net monetary benefits (INB) of the treatment algorithm versus usual care. RESULTS: The mean [SD] quality of life at 30 days and 6 months was similar between the treatment groups (at 6 months, intervention group 0.73 [0.28] versus usual care group 0.71 [0.30]; mean gain 0.03 [95 % confidence interval (CI) -0.01 to 0.08]). At 6 months, survival, mean QALYs and mean healthcare costs (intervention group L8574 versus usual care group L8974) were also similar. At the cost-effectiveness threshold of L20,000 per QALY gained, the incremental net benefit of haemodynamic therapy over the patients' lifetime was positive (L4168 [95 % CI -L3063 to L11,398]). This corresponds to an 87 % probability that this intervention is cost-effective. CONCLUSIONS: Cardiac output guided haemodynamic therapy algorithm was associated with an average cost reduction and improvement in QALY and is likely to be cost-effective. Further research is needed to confirm the clinical and cost-effectiveness of this treatment. TRIAL REGISTRATION: ISRCTN04386758. PMID- 26674493 TI - Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit. AB - Detecting danger is one of the foremost tasks for a neural system. Larval parasitoids constitute clear danger to Drosophila, as up to 80% of fly larvae become parasitized in nature. We show that Drosophila melanogaster larvae and adults avoid sites smelling of the main parasitoid enemies, Leptopilina wasps. This avoidance is mediated via a highly specific olfactory sensory neuron (OSN) type. While the larval OSN expresses the olfactory receptor Or49a and is tuned to the Leptopilina odor iridomyrmecin, the adult expresses both Or49a and Or85f and in addition detects the wasp odors actinidine and nepetalactol. The information is transferred via projection neurons to a specific part of the lateral horn known to be involved in mediating avoidance. Drosophila has thus developed a dedicated circuit to detect a life-threatening enemy based on the smell of its semiochemicals. Such an enemy-detecting olfactory circuit has earlier only been characterized in mice and nematodes. PMID- 26674495 TI - Information resources to aid parental decision-making on when to seek medical care for their acutely sick child: a narrative systematic review. AB - OBJECTIVE: To identify the effectiveness of information resources to help parents decide when to seek medical care for an acutely sick child under 5 years of age, including the identification of factors influencing effectiveness, by systematically reviewing the literature. METHODS: 5 databases and 5 websites were systematically searched using a combination of terms on children, parents, education, acute childhood illness. A narrative approach, assessing quality via the Mixed Methods Appraisal Tool, was used due to non-comparable research designs. RESULTS: 22 studies met the inclusion criteria: 9 randomised control trials, 8 non-randomised intervention studies, 2 qualitative descriptive studies, 2 qualitative studies and 1 mixed method study. Consultation frequency (15 studies), knowledge (9 studies), anxiety/reassurance (7 studies), confidence (4 studies) satisfaction (4 studies) and antibiotic prescription (4 studies) were used as measures of effectiveness. Quality of the studies was variable but themes supported information needing to be relevant and comprehensive to enable parents to manage an episode of minor illness Interventions addressing a range of symptoms along with assessment and management of childhood illness, appeared to have the greatest impact on the reported measures. The majority of interventions had limited impact on consultation frequencies, No conclusive evidence can be drawn from studies measuring other outcomes. CONCLUSIONS: Findings confirm that information needs to be relevant and comprehensive to enable parents to manage an episode of minor illness. Incomplete information leaves parents still needing to seek help and irrelevant information appears to reduce parents' trust in the intervention. Interventions are more likely to be effective if they are also delivered in non-stressful environments such as the home and are coproduced with parents. PMID- 26674496 TI - Primary care consultation rates among people with and without severe mental illness: a UK cohort study using the Clinical Practice Research Datalink. AB - OBJECTIVES: Little is known about service utilisation by patients with severe mental illness (SMI) in UK primary care. We examined their consultation rate patterns and whether they were impacted by the introduction of the Quality and Outcomes Framework (QOF), in 2004. DESIGN: Retrospective cohort study using individual patient data collected from 2000 to 2012. SETTING: 627 general practices contributing to the Clinical Practice Research Datalink, a large UK primary care database. PARTICIPANTS: SMI cases (346,551) matched to 5 individuals without SMI (1,732,755) on age, gender and general practice. OUTCOME MEASURES: Consultation rates were calculated for both groups, across 3 types: face-to-face (primary outcome), telephone and other (not only consultations but including administrative tasks). Poisson regression analyses were used to identify predictors of consultation rates and calculate adjusted consultation rates. Interrupted time-series analysis was used to quantify the effect of the QOF. RESULTS: Over the study period, face-to-face consultations in primary care remained relatively stable in the matched control group (between 4.5 and 4.9 per annum) but increased for people with SMI (8.8-10.9). Women and older patients consulted more frequently in the SMI and the matched control groups, across all 3 consultation types. Following the introduction of the QOF, there was an increase in the annual trend of face-to-face consultation for people with SMI (average increase of 0.19 consultations per patient per year, 95% CI 0.02 to 0.36), which was not observed for the control group (estimates across groups statistically different, p=0.022). CONCLUSIONS: The introduction of the QOF was associated with increases in the frequency of monitoring and in the average number of reported comorbidities for patients with SMI. This suggests that the QOF scheme successfully incentivised practices to improve their monitoring of the mental and physical health of this group of patients. PMID- 26674498 TI - Exercise Programme in Endometrial Cancer; Protocol of the Feasibility and Acceptability Survivorship Trial (EPEC-FAST). AB - INTRODUCTION: Obesity has been associated with impaired quality of life and poorer outcomes in endometrial cancer survivors. Lifestyle interventions promoting exercise and weight reduction have been proposed for survivorship care. However, studies evaluating exercise programmes for endometrial cancer survivors are lacking. PURPOSE: The objective of this study is to evaluate the feasibility of an individualised exercise intervention for endometrial cancer survivors to improve quality of life. METHODS AND ANALYSIS: This is a feasibility study in which women will undergo a 10-week exercise programme with a personal trainer. The study population comprises women with confirmed diagnosis of endometrial cancer, who have completed surgical treatment with curative intent, and are aged 18 years or older. The study will take place at the Royal Cornwall Hospital Trust, UK. Feasibility will be evaluated in terms of recruitment, adherence and compliance to the programme. Secondary outcomes are quality of life, psychological distress, fatigue, pain and complication rates. In addition, the acceptability of the programme will be assessed. ETHICS AND DISSEMINATION: Ethical approval was obtained through the Exeter NRES Committee. The study results will be used to optimise the intervention content, and may serve as the foundation for a larger definitive trial. Results will be disseminated through peer-review journals, congresses, relevant clinical groups and presented on the Trust's website. TRIAL REGISTRATION NUMBER: NCT02367950; pre-results. PMID- 26674497 TI - MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol. AB - INTRODUCTION: Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD. METHODS AND ANALYSIS: Adult patients affected by PAOD at stages III and IV of Leriche-Fontaine classification, who are opioid-naive, and who have been admitted to our Acute Pain Service for intractable pain, will be eligible. Patients will be randomised to the control group, treated with standard therapy (oxycodone and pregabalin) plus placebo for 2 weeks, or to the experimental group (standard therapy plus magnesium oxide). Patients will be evaluated on days 0, 2, 4, 6, 8, 12 and 14; the following information will being collected: daily oxycodone dose; average and maximum pain (Numerical Rating Scale); pain relief (Pain Relief Scale); characteristics of the pain (Neuropathic Pain Scale); impact of pain on the patient's daily activities (Brief Pain Inventory). The primary outcome will be oxycodone dosage needed to achieve satisfactory analgaesia on day 14. Secondary outcomes will be pain relief on day 2, time needed to achieve satisfactory analgaesia and time needed to achieve a pain reduction of 50%. A sample size calculation was performed for the primary outcome, which estimated a required sample size of 150 patients (75 per group). ETHICS AND DISSEMINATION: Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy. Trial results will be disseminated through scientific journal manuscripts and scientific conference presentations. TRIAL REGISTRATION NUMBER: NCT02455726. PMID- 26674500 TI - Trends in serum creatinine testing in Oxfordshire, UK, 1993-2013: a population based cohort study. AB - OBJECTIVES: To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time. DESIGN: Retrospective study of all serum creatinine, urine albumin and urine creatinine tests. SETTING: Primary and secondary care in Oxfordshire from 1993 to 2013. PARTICIPANTS: Unselected population of 1,220,447 people. MAIN OUTCOME MEASURES: The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored. RESULTS: Creatinine requests from primary care increased steadily from 1997 and exceeded 220,000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m(2)) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3-5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year. CONCLUSIONS: There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful. PMID- 26674501 TI - Impact of geography on the control of type 2 diabetes mellitus: a review of geocoded clinical data from general practice. AB - OBJECTIVE: To review the clinical data for people with diabetes mellitus with reference to their location and clinical care in a general practice in Australia. MATERIALS AND METHODS: Patient data were extracted from a general practice in Western Australia. Iterative data-cleansing steps were taken. Data were grouped into Statistical Area level 1 (SA1), designated as the smallest geographical area associated with the Census of Population and Housing. The data were analysed to identify if SA1s with people aged 70 years and older, and with relatively high glycosylated haemoglobin (HbA1c) were significantly clustered, and whether this was associated with their medical consultation rate and treatment. The analysis included Cluster and Outlier Analysis using Moran's I test. RESULTS: The overall median age of the population was 70 years with more males than females, 53% and 47%, respectively. Older people (>70 years) with relatively high HbA1c comprised 9.3% of all people with diabetes in the sample, and were clustered around two 'hotspot' locations. These 111 patients do not attend the practice more or less often than people with diabetes living elsewhere in the practice (p=0.098). There was some evidence that they were more likely to be recorded as having consulted with regard to other chronic diseases. The average number of prescribed medicines over a 13-month time period, per person in the hotspots, was 4.6 compared with 5.1 in other locations (p=0.26). Their prescribed therapy was deemed to be consistent with the management of people with diabetes in other locations with reference to the relevant diabetes guidelines. CONCLUSIONS: Older patients with relatively high HbA1c are clustered in two locations within the practice area. Their hyperglycaemia and ongoing cardiovascular risk indicates causes other than therapeutic inertia. The causes may be related to the social determinants of health, which are influenced by geography. PMID- 26674499 TI - VITALITY trial: protocol for a randomised controlled trial to establish the role of postnatal vitamin D supplementation in infant immune health. AB - INTRODUCTION: Postnatal vitamin D supplementation may be associated with a reduction in IgE-mediated food allergy, lower respiratory tract infections and improved bone health. Countries in the Northern hemisphere recommend universal infant vitamin D supplementation to optimise early vitamin D levels, despite the absence of large trials proving safety or efficacy for any disease outcome. With the aim of determining the clinical and cost-effectiveness of daily vitamin D supplementation in breastfed infants from age 6-8 weeks to 12 months of age, we have started a double-blind, randomised, placebo-controlled trial of daily 400 IU vitamin D supplementation during the first year of life, VITALITY. METHODS ND ANALYSIS: Infants (n=3012) who are fully breastfed and not receiving vitamin D supplementation will be recruited at the time of their first immunisation, from council-led immunisation clinics throughout metropolitan Melbourne, Australia. The primary outcome is challenge-proven food allergy at 12 months of age. Secondary outcomes are food sensitisation (positive skin prick test), number of lower respiratory infections (through hospital linkage), moderately-severe and persistent eczema (by history and examination) and vitamin D deficiency (serum vitamin D <50 nmol/L) at age 12 months. The trial is underway and the first 130 participants have been recruited. ETHICS AND DISSEMINATION: The VITALITY study is approved by the Royal Children's Hospital (RCH) Human Research Ethics Committee (#34168). Outcomes will be disseminated through publication and will be presented at scientific conferences. TRIAL REGISTRATION NUMBERS: ANZCTR12614000334606 and NCT02112734; pre-results. PMID- 26674502 TI - Correlation between symptoms and objective findings may improve the symptom-based diagnosis of chronic rhinosinusitis for primary care and epidemiological studies. AB - BACKGROUND: In primary care and epidemiological studies of chronic rhinosinusitis (CRS), symptom-based diagnosis is common, yet limited, because endoscopic and radiological signs are not considered. OBJECTIVES: To evaluate the correlation between symptoms and objective findings of CRS to improve its symptom-based diagnosis for primary care and epidemiological studies by using data from a large scale nationwide epidemiological study, the Korean National Health and Nutrition Examination Survey (KNHANES). DESIGN: Cross-sectional study. SETTING: Data from 2008 to 2012 KNHANES. PARTICIPANTS: 29,225 Adults aged >19 years. OUTCOME MEASURES: Questionnaires targeted two major (nasal blockage and anterior/posterior nasal drip) and two minor (facial pain/pressure and reduction or loss of smell) symptoms. Nasal polyps or mucopurulent discharge from the middle meatus was defined as positive endoscopic findings for diagnosing CRS. RESULTS: Of the four symptoms, reduction or loss of smell was the symptom most significantly related to positive endoscopic findings in multivariable analysis (OR=1.936 (95% CI 1.604 to 2.337)). The combinations of symptoms showed higher ORs than individual symptoms and combinations of reduction or loss of smell with other symptoms were statistically more reliable for positive endoscopic findings than other combinations. CONCLUSIONS: Our results show that reduction or loss of smell was the symptom most significantly related to positive nasal endoscopic findings. Therefore, symptom-based diagnosis of CRS can be improved by considering reduction or loss of smell as an important symptom for positive endoscopic findings of CRS. PMID- 26674504 TI - Survey of the capacity for essential surgery and anaesthesia services in Papua New Guinea. AB - OBJECTIVE: To assess capacity to provide essential surgical services including emergency, obstetric and anaesthesia care in Papua New Guinea (PNG) in order to support planning for relevant post-2015 sustainable development goals for PNG. DESIGN: Cross-sectional survey. SETTING: Hospitals and health facilities in PNG. PARTICIPANTS: 21 facilities including 3 national/provincial hospitals, 11 district/rural hospitals, and 7 health centres. OUTCOME MEASURES: The WHO Situational Analysis Tool to Assess Emergency and Essential Surgical Care (WHO SAT) was used to measure each participating facility's capacity to deliver essential surgery and anaesthesia services, including 108 items related to relevant infrastructure, human resources, interventions and equipment. RESULTS: While major surgical procedures were provided at each hospital, fewer than 30% had uninterrupted access to oxygen, and 57% had uninterrupted access to resuscitation bag and mask. Most hospitals reported capacity to provide general anaesthesia, though few hospitals reported having at least one certified surgeon, obstetrician and anaesthesiologist. Access to anaesthetic machines, pulse oximetry and blood bank was severely limited. Many non-hospital health centres providing basic surgical procedures, but almost none had uninterrupted access to electricity, running water, oxygen and basic supplies for resuscitation, airway management and obstetric services. CONCLUSIONS: Capacity for essential surgery and anaesthesia services is severely limited in PNG due to shortfalls in physical infrastructure, human resources, and basic equipment and supplies. Achieving post 2015 sustainable development goals, including universal healthcare, will require significant investment in surgery and anaesthesia capacity in PNG. PMID- 26674503 TI - Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system). AB - PURPOSE: The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events. PARTICIPANTS: Between March 2013 and October 2014, a total of 3000 men and women aged >= 60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%). FINDINGS TO DATE: Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at -80 degrees C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men. FUTURE PLANS: Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration. PMID- 26674505 TI - Therapeutic management of complex anal fistulas by installing a nitinol closure clip: study protocol of a multicentric randomised controlled trial--FISCLOSE. AB - INTRODUCTION: Complex anal fistulas are responsible for pain, faecal incontinence and impaired quality of life. The rectal mucosa advancement flap (RMAF) procedure to cover the internal opening of the fistula remains a strategy of choice. However, a new procedure for closing anal fistulas is now available with the use of a nitinol closure clip (OTSC Proctology, OVESCO), which should ensure a better healing rate. This procedure is currently becoming more widespread, though without robust scientific validation, and it is therefore essential to carry out a prospective evaluation in order to determine the efficacy and safety of this new medical device for complex anal fistulas. METHODS AND ANALYSIS: The FISCLOSE trial is aimed at evaluating the efficacy and safety of a nitinol closure clip compared to the RMAF procedure for the management of complex anal fistulas. This trial is a prospective, randomised, controlled, single-blind, bicentre and interventional study. Patients (n=46 per group) will be randomly assigned for management with either a closure clip or RMAF. The main objectives are to improve the healing rate of the anal fistula, lessen the postoperative pain and faecal incontinency, enhance the quality of life, and lower the number of reinterventions and therapeutic management costs. The primary outcome is the proportion of patients with a healed fistula at 3 months. The secondary outcomes are anal fistula healing (6 and 12 months), proctological pain (visual analogue scale), the faecal incontinence score (Jorge and Wexner questionnaire), digestive disorders and quality of life (Gastrointestinal Quality of Life Index and Euroqol EQ5D-3 L) up to 1 year. ETHICS AND DISSEMINATION: The study was approved by an independent medical ethics committee 1 (IRB00008526, CPP Sud-Est 6, Clermont Ferrand, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international congresses. TRIAL REGISTRATION NUMBER: NCT02336867; pre-result. PMID- 26674506 TI - Identifying research priorities in anaesthesia and perioperative care: final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership. AB - OBJECTIVE: To identify research priorities for Anaesthesia and Perioperative Medicine. DESIGN: Prospective surveys and consensus meetings guided by an independent adviser. SETTING: UK. PARTICIPANTS: 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. OUTCOMES: First 'ideas-gathering' survey: Free text research ideas and suggestions. Second 'prioritisation' survey: Shortlist of 'summary' research questions (derived from the first survey) ranked by respondents in order of priority. Final 'top ten': Agreed by consensus at a final prioritisation workshop. RESULTS: First survey: 1420 suggestions received from 623 respondents (49% patients/public) were refined into a shortlist of 92 'summary' questions. Second survey: 1718 respondents each nominated up to 10 questions as research priorities. Top ten: The 25 highest-ranked questions advanced to the final workshop, where 23 stakeholders (13 professional, 10 patient/carer) agreed the 10 most important questions: ? What can we do to stop patients developing chronic pain after surgery? ? How can patient care around the time of emergency surgery be improved? ? What long-term harm may result from anaesthesia, particularly following repeated anaesthetics?? What outcomes should we use to measure the 'success' of anaesthesia and perioperative care? ? How can we improve recovery from surgery for elderly patients? ? For which patients does regional anaesthesia give better outcomes than general anaesthesia? ? What are the effects of anaesthesia on the developing brain? ? Do enhanced recovery programmes improve short and long-term outcomes? ? How can preoperative exercise or fitness training, including physiotherapy, improve outcomes after surgery? ? How can we improve communication between the teams looking after patients throughout their surgical journey? CONCLUSIONS: Almost 2000 stakeholders contributed their views regarding anaesthetic and perioperative research priorities. This is the largest example of patient and public involvement in shaping anaesthetic and perioperative research to date. PMID- 26674507 TI - Protocol for a mixed-methods longitudinal study to identify factors influencing return to work in the over 50s participating in the UK Work Programme: Supporting Older People into Employment (SOPIE). AB - INTRODUCTION: Increasing employment among older workers is a policy priority given the increase in life expectancy and the drop in labour force participation after the age of 50. Reasons for this drop are complex but include poor health, age discrimination, inadequate skills/qualifications and caring roles; however, limited evidence exists on how best to support this group back to work. The Work Programme is the UK Government's flagship policy to facilitate return to work (RTW) among those at risk of long-term unemployment. 'Supporting Older People Into Employment' (SOPIE) is a mixed-methods longitudinal study involving a collaboration between academics and a major Work Programme provider (Ingeus). The study will investigate the relationship between health, worklessness and the RTW process for the over 50s. METHODS AND ANALYSIS: There are three main study components. Embedded fieldwork will document the data routinely collected by Ingeus and the key interventions/activities delivered. The quantitative study investigates approximately 14,000 individuals (aged 16-64 years, with 20% aged over 50) who entered the Ingeus Work Programme (referred to as 'clients') in a 16 month period in Scotland and were followed up for 2 years. Employment outcomes (including progression towards work) and how they differ by client characteristics (including health), intervention components received and external factors will be investigated. The qualitative component will explore the experiences of clients and Ingeus staff, to better understand the interactions between health and (un)employment, Work Programme delivery, and how employment services can be better tailored to the needs of the over 50s. ETHICS AND DISSEMINATION: Ethical approval was received from the University of Glasgow College of Social Sciences Research Ethics Committee (application number 400140186). RESULTS: Results will be disseminated through journal articles, national and international conferences. Findings will inform current and future welfare-to-work and job retention initiatives to extend healthy working lives. PMID- 26674508 TI - Reconfigurable Solid-state Dye-doped Polymer Ring Resonator Lasers. AB - This paper presents wavelength configurable on-chip solid-state ring lasers fabricated by a single-mask standard lithography. The single- and coupled-ring resonator hosts were fabricated on a fused-silica wafer and filled with 3,3' Diethyloxacarbocyanine iodide (CY3), Rhodamine 6G (R6G), and 3,3' Diethylthiadicarbocyanine iodide (CY5)-doped polymer as the reconfigurable gain media. The recorded lasing threshold was ~220 nJ/mm(2) per pulse for the single ring resonator laser with R6G, marking the lowest threshold shown by solid-state dye-doped polymer lasers fabricated with a standard lithography process on a chip. A single-mode lasing from a coupled-ring resonator system with the lasing threshold of ~360 nJ/mm(2) per pulse was also demonstrated through the Vernier effect. The renewability of the dye-doped polymer was examined by removing and redepositing the dye-doped polymer on the same resonator hosts for multiple cycles. We recorded consistent emissions from the devices for all trials, suggesting the feasibility of employing this technology for numerous photonic and biochemical sensing applications that entail for sustainable, reconfigurable, and low lasing threshold coherent light sources on a chip. PMID- 26674509 TI - Tobacco Control in India; A Myth or Reality- Five Year Retrospective Analysis Using WHO MPOWER for Tobacco Control. AB - INTRODUCTION: Tobacco use is a major public health challenge in India and government of India has taken various initiatives for tobacco control in the country. India was among the first few countries to ratify WHO the Framework Convention on Tobacco Control (WHO FCTC) in 2004 and to make it easy, WHO introduced the MPOWER measures. OBJECTIVE: This study aimed to quantify the implementation of MPOWER tobacco control policies in India. MATERIALS AND METHODS: In this retrospective analysis information was collected from the WHO report on the Global Tobacco Epidemic Program, India for the year 2009, 2011 and 2013 using MPOWER and this analysis was based on the checklist which was designed previously by Iranian and international tobacco control specialists in their study on tobacco control and its cut-offs were set according to the scoring of key sections of the MPOWER 2011 report. RESULTS: In this study India was ranked by scores and these scores were obtained from each indicator for each activity. The highest scores were achieved in 2013 and there are marked increase in scores in health warning on cigarette packages but as far as the cessation programmes and taxation is concerned, there is decline in the progress. CONCLUSION: MPOWER programmes are accepted in the India but there is considerable room for improvement as we are still far from the ideal situation. PMID- 26674510 TI - Rethinking Adolescent Inpatient Psychiatric Care: The Importance of Integrated Interventions for Suicidal Youth With Substance Use Problems. AB - Adolescents psychiatrically hospitalized following a suicide attempt are at high risk for a repeat attempt or suicide completion, and substance use is consistently implicated as a risk factor for continued suicidal behavior in adolescents. Despite this knowledge, there have been few studies that have investigated the effectiveness of combined suicidality and substance use interventions within acute psychiatric care settings for suicidal youth with substance use problems. While social workers are well-positioned to deliver such interventions, greater emphasis on teaching integrated therapeutic techniques in social work curriculum and professional training is needed to ensure their implementation. PMID- 26674511 TI - Neurolaw: recognizing opportunities and challenges for psychiatry. PMID- 26674512 TI - Successful management of clozapine adverse effects with extended (alternate day) antipsychotic dosing in a patient with schizophrenia. PMID- 26674513 TI - PRE-OPERATIVE LOW BACK PAIN NEGATIVELY AFFECTS SELF-REPORTED FUNCTION IN INDIVIDUALS UNDERGOING HIP ARTHROSCOPY. AB - BACKGROUND/PURPOSE: Low back pain (LBP) is a common source of disability in adults and highly prevalent in patients with painful hip pathology. Persistent LBP after hip arthroplasty is associated with lower self-reported function, however, the effect of pre-operative LBP in patients undergoing hip arthroscopy for FAI has not been evaluated. The purpose of this study was to determine whether improvements in self-reported hip function following arthroscopic surgery for femoroacetabular impingement (FAI) differed between those with and without reports of pre-operative low back pain. STUDY DESIGN: Cohort. METHODS: Three hundred eighteen subjects undergoing primary hip arthroscopy for clinically and radiographically-confirmed FAI were recruited and consented. One hundred fifty six of these subjects completed the International Hip Outcomes Tool (iHOT-33) and the Hip Outcome Score Activities of Daily Living Subscale (HOS-ADL) before, and six and 12 months after surgery. Subjects were grouped based on the self-reported presence or absence of LBP prior to arthroscopy. A repeated measures analysis of variance was used to determine the effects of time and low back pain on iHOT-33 and HOS-ADL scores. RESULTS: Seventy-five of 156 subjects (48.1%) reported LBP prior to surgery. A main effect of time was found for both outcome measures (p<0.001), demonstrating improvement in self-reported outcomes over the testing period. There was a main effect of group for the iHOT-33 (LBP: 52.0 [47.9,56.0]; no LBP 57.9 [53.9,61.8]; p = 0.043) but not for the HOS-ADL (LBP: 75.2 [72.2,78.2]; no LBP 78.8 [75.9,81.7]; p = 0.088) indicating that subjects with pre-operative LBP had poorer self-reported function per the iHOT-33 compared to those without LBP. CONCLUSION: Self-reported hip function scores improved regardless of the presence of pre-operative LBP; however subjects with LBP reported poorer self-reported function per the iHOT-33 as compared to those without LBP up to 12 months post-operatively. LEVEL OF EVIDENCE: 3c. PMID- 26674515 TI - Relevance of ultrasound examination in general practice. A case report of a patient with autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease is a genetic disorder which results in the development of multiple cysts in the kidneys and other parenchymal organs. The two genes in which mutations are known to cause autosomal dominant polycystic kidney disease are PKD1 and PKD2. Approximately 50% of individuals with autosomal dominant polycystic kidney disease will develop end-stage renal disease by the age of 60. Early stages of the disease are usually asymptomatic and at the moment of establishing a definitive diagnosis, complications and associated disorders, including end-stage renal disease, occur frequently. About 95% of individuals with autosomal dominant polycystic kidney disease have an affected parent and about 5% have a de novo mutation. Each child of an affected individual has a 50% chance of inheriting the mutation. The first symptoms of disease usually develop in the third or fourth decades of life. Imaging examinations of relatives at risk allow for an early detection when no clinical symptoms are present as well as enable treatment of complications and associated disorders. Ultrasound examination as a basic and minimally invasive imaging technique can be easily used in general practice. In the majority of patients with autosomal dominant polycystic kidney disease, sonography allows for a certain and reliable diagnosis of this disease. Additionally, it enables to perform follow-up examinations both of the patient and their family. The possibility of ultrasound imaging in general practice broadens clinical examination and facilitates establishing a proper diagnosis. The paper presents a case report of a patient with autosomal dominant polycystic kidney disease. Its aim was to present the relevance of ultrasound examination in general practice. PMID- 26674514 TI - Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure. AB - The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet) for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14 fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm) or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs) after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid) concentrations but no clear dose-related increases in DEG numbers. PMID- 26674516 TI - Serum Basal Paraoxonase 1 Activity as an Additional Liver Function Test for the Evaluation of Patients with Chronic Hepatitis. AB - BACKGROUND: The diagnostic accuracy of currently available standard panel of liver function tests is not satisfactory for the reliable diagnosis of chronic liver disorders. Earlier studies have reported that serum basal paraoxonase 1 (PON1) activity measurement may add a significant contribution to the liver function tests. AIM: To assess whether the measurement of serum basal paraoxonase 1 (PON1) activity would be useful as an index of liver function status in chronic hepatitis patients. MATERIALS AND METHODS: The study included 50 chronic hepatitis patients and 50 apparently healthy controls based on inclusion & exclusion criteria. In all the subjects, standard liver function tests were analysed by using standard methods. Basal PON1 activity was estimated using spectrophotometric method by the hydrolysis of p-nitrophenylacetate. Student t test, Pearson's correlation coefficient, diagnostic validity tests and ROC curve analysis were the methods used for the statistical analysis of the data. RESULTS: The serum basal PON1 activity was significantly decreased in chronic hepatitis cases when compared to controls (p< 0.001). Also basal PON1 activity was positively correlated with serum total protein and albumin, and negatively correlated with serum total bilirubin, alanine amino transferase (ALT), and alkaline phosphatase (ALP) (p< 0.001) in chronic hepatitis cases but not in healthy controls. Diagnostic validity tests showed, basal PON1 activity was a better discriminator of chronic hepatitis than total protein, albumin and ALP with sensitivity of 68%, specificity of 100%, positive predictive value of 100% and negative predictive value of 75%. ROC curve analysis demonstrated highest diagnostic accuracy for ALT (AUC = 0.999) followed by PON1 (AUC = 0.990), total bilirubin (AUC = 0.977), ALP (AUC = 0.904), total protein (AUC = 0.790) and albumin (AUC = 0.595). CONCLUSION: Diagnostic accuracy of serum PON1 activity is better than total bilirubin, total protein, albumin and ALP. PON1 activity measurement could significantly improve the current efficiency of a laboratory's evaluation of patients with suspected chronic hepatitis. PMID- 26674517 TI - Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis. AB - BACKGROUND: Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples. METHODS: TB related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods. RESULTS: Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%). CONCLUSIONS: Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical application. PMID- 26674518 TI - Totally robotic vs 3D laparoscopic colectomy: A single centers preliminary experience. AB - AIM: To compare robotic and three-dimensional (3D) laparoscopic colectomy based on the literature and our preliminary experience. METHODS: This retrospective observational study compared operative measures and postoperative outcomes between laparoscopic 3D and robotic colectomy for cancer. From September 2013 to September 2014, 24 robotic colectomies and 23 3D laparoscopic colectomy were performed at our Department. Data were analyzed and reported both by approach and by colectomy side. Robotic left colectomy (RL) vs laparoscopic 3D left colectomy (LL 3D) and Robotic right colectomy (RR) vs laparoscopic 3D (LR 3D). Rectal cancer procedures were not included. RESULTS: There were 18 RR and 11 LR 3D, 6 RL and 12 LL 3D. As regards LR 3D, extracorporeal anastomosis (EA) was performed in 7 patients and intracorporeal anastomosis (IA) in 4; the RR group included 14 IA and 4 EA. There was no mortality. Median operative time was higher for the robotic group while conversion rate (12.5% vs 13%) and lymph nodes removed (14 vs 13) were similar for both. First flatus time was 1 d for RR and 2 d the other patient groups. Oral intake was resumed in 1 d by LR and in 2 d by the other patients (P = 0.012). Overall cost was ?4950 and ?1950 for RL and LL 3D, and ?4450 and ?1450 for RR and LR 3D, respectively. CONCLUSION: There were no differences between RR and LR 3D, except that IA was easier with RR, and probably contributed with the learning curve to the longer operative time recorded. Both techniques offer similar advantages for the patient with significantly different costs. In left colectomies robotic colectomy provided better outcomes, especially in resections approaching the rectum. PMID- 26674519 TI - Detection of unruptured intracranial aneurysms on noninvasive imaging. Is there still a role for digital subtraction angiography? AB - BACKGROUND: To determine the utility of digital subtraction angiography (DSA) in patients with unruptured intracranial aneurysms (UIA) detected on noninvasive imaging, such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA). The follow-up of patients with untreated UIAs involves serial imaging; however, this diagnosis may be based on false positive (FP) results. We examined the incidence of FPs in our institutional series. METHODS: DSAs performed at our institution from January 2011 to June 2014 were retrospectively reviewed and patients referred with UIA detected on noninvasive imaging were selected. Clinical presentation as well as aneurysm location, size, and number reported on DSA and noninvasive imaging were assessed. RESULTS: Two hundred and eighty six patients (mean age 56.8 years, female 74.8%) with a total of 355 UIA were included. Thirty-one patients had a symptomatic presentation. Analysis per patient showed the pooled FP rate of noninvasive imaging was 15%. MRA FP was 13% (22/171) and CTA FP was 18% (22/120). FP increased significantly with aneurysm size < 3.5 mm on MRA (P < 0.001) and <4.0 mm on CTA (P = 0.01). Mean aneurysm size among symptomatic patients was significantly larger (P < 0.001) as compared to the incidental group (17.8 vs. 7.7 mm). No location was significantly susceptible to false detection of aneurysms. CONCLUSION: DSA detection of FP UIA diagnosed on noninvasive imaging is significantly higher for aneurysms <4.0 mm. Accurate diagnosis with DSA may eliminate the need for further follow-up and its associated negative psychological and economic effects. Within the limitations of this retrospective study, we conclude that DSA has a diagnostic role in small aneurysms detected on noninvasive imaging. PMID- 26674520 TI - Simvastatin augmentation for recent-onset psychotic disorder: A study protocol. PMID- 26674521 TI - Epigenetic Biomarkers for the Early Detection of Gastrointestinal Cancer. AB - BACKGROUND: Gastric cancer and colorectal cancer, the two most frequent cancers within the gastrointestinal tract, account for a large proportion of human malignancies worldwide. The initiation and progression of gastrointestinal cancer (GIC) is controlled by both genetic and epigenetic events. Epigenetic alterations, including changes in DNA methylation, specific histone modifications, chromatin remodeling and noncoding RNA-mediated gene silencing, are potentially reversible and heritable. SUMMARY: In this article, we summarize the current advances in epigenetic biomarkers as potential substrates for GIC detection. The combined screening of a panel of methylated genes, hyperacetylated histones, microRNAs or other noncoding RNAs is currently under evaluation to improve sensitivity. KEY MESSAGE: Current studies concentrated on the development of cost-effective epigenetic diagnostic biomarkers for GIC based on noninvasive blood or stool samples. The combined blood or stool test with a relatively high sensitivity could be a cost-effective screening tool for the detection of patients with asymptomatic cancers who could therefore choose whether or not to go for further examinations, such as endoscopy or colonoscopy. PRACTICAL IMPLICATIONS: A better understanding of epigenetic mechanisms has not only offered new insights into a deeper understanding of the underlying mechanisms of carcinogenesis, but has also allowed identification of clinically relevant putative biomarkers for the early detection, disease monitoring, prognosis and risk assessment of GIC. In particular, noninvasive biomarkers in serum or fecal samples for the detection of GIC could have potential for better compliance and can be incorporated into routine clinical practice in the foreseeable future, pending their validation in large-scale prospective trials. PMID- 26674522 TI - Evaluation of Shear Bond Strength of Feldspathic CAD/CAM Ceramic with Dentin using 2 Bonding Agents and 2 Surface Treatments- An Invitro Study. AB - BACKGROUND: All ceramics are the material of choice for aesthetic tooth replacements. The success of all ceramic restoration depends on the bond between the ceramic and the tooth surface hence this study was done to evaluate the shear bond strength of Feldspathic CAD/CAM ceramic with <5% hydrofluoric acid and hydrofluoric acid combined with silane coupling agent. AIM: To evaluate the shear bond strength of Feldspathic CAD/CAM ceramic with Dentin using bonding agents Prime & Bond NT, XenoIII and surface treatments <5% hydrofluric acid, hydrofluric acid combined with silane coupling agent. MATERIALS AND METHODS: Forty cylinders with 6mm diameter and 5mm height were milled from CEREC Blocs through CAD/CAM technology. Cerec blocks were bonded to etch freshly extracted tooth surface using a self etch and total etch bonding agent. The samples were divided into 4 groups. Group A1-Ceramic cylinders were treated with < 5% HF and bonded using Prime & Bond NT and Variolink II. Group A2- treated with < 5% HF and silane coupling agent and bonded same as group A1. Group B1- treated with < 5% HF and bonded using Xeno III and Variolink II. Group B2- treated with < 5% HF and silane coupling agent, and bonded same as Group A3. The shear bond strength was evaluated after 24 hours by Storing in distilled water in Instron 3385 universal testing machine with 10-KN force. RESULTS: Statistical analysis was done using student's t-test and Lavene's test. The p-value <0.05 shows significant difference in bond strength between A1 and A2 & B1and B2. CONCLUSION: The application of a silane coupling agent to the ceramic surface after etching with hydrofluoric acid increased the adhesion strength with both bonding agents. Student's t-test revealed a significant effect of silanization. PMID- 26674523 TI - Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival. AB - OBJECTIVE: To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC). METHODS: This retrospective study included 114 patients with stage I-IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association. RESULTS: In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412-7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367-7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573-9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613-49.711], 39.717 [35.471-43.964], 30.197 [24.030-36.327], respectively. CONCLUSIONS: Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6 integrins and GS, and also between the ITGA3 integrin and DFS, in patients with colorectal tumours. A risk scoring system based on detected hyperexpression of 0, 1, or 2 markers (e.g., ITGAV and/or ITGA6) was also found to accurately correlate with the GS curves generated for the present cohort. PMID- 26674524 TI - Lower Extremity Overuse Conditions Affecting Figure Skaters During Daily Training. AB - BACKGROUND: Most ice figure skaters train and compete with ongoing issues in the lower extremities, which are often overlooked by the skaters and considered injuries only when they prevent the athletes from skating. Although not severe, these conditions impair the quality of daily training and compromise the skaters' state of mind and performances. PURPOSE: (1) To determine the point prevalence of the ongoing lower extremity overuse conditions in a population of ice figure skaters of all ages and levels and (2) to identify the risk factors contributing to the development of the most common ongoing conditions. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: A total of 95 skaters of all ages and skating levels were evaluated in a single examination in the middle of the competitive season. Data collection consisted of a questionnaire, clinical examination, and measurement of the skaters' characteristics and the equipment used. RESULTS: Retrocalcaneal bursitis was the most common problem, affecting at least 1 foot in 34% of the skaters evaluated, followed by posterior heel skin calluses and superficial calcaneal bursitis, which affected 29% and 28% of skaters, respectively. The prevalence of the majority of these conditions was 10% to 32% higher in elite skaters than in nonelite skaters. Higher boot-foot length difference was associated with greater risk of superficial calcaneal bursitis in the landing foot of elite skaters, while higher body weight and greater in-skate ankle flexibility were associated with the development of retrocalcaneal bursitis in nonelite skaters. Only 30 skaters (32%) wore the appropriate boot size, while 57 skaters (51%) could not dorsiflex their ankles properly while wearing skates. CONCLUSION: The heel represents a major area of concern for the high prevalence of calcaneal bursitis and calluses in proximity of the Achilles tendon, suggesting that improvements on the boot heel cup design should take priority. The association of bursitis with higher in-skate ankle flexibility suggests that these conditions may be the results of a process developing when the ankle is bending within the boot. Also, since wearing oversized boots is a major risk factor for the development of subcutaneous bursitis and skin abrasions, boot retailers should be better educated to sell the appropriate boot size to the skaters. PMID- 26674525 TI - Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy that has a poor prognosis because there is lack of methods for early diagnosis. We aimed to utilize two serum long non-coding RNAs (lncRNAs), uc001ncr and AX800134, to diagnose hepatitis B virus (HBV)-positive HCC. METHODS: lncRNA microarrays were utilized to measure the differential expression of lncRNAs between tumor tissues and corresponding non-tumor tissues in HBV-positive hapatocellular carcinoma. uc001ncr and AX800134 were selected as candidate lncRNAs and detected in three independent cohorts containing a total of 684 participants (healthy individuals and chronic HBV patients and HBV-positive HCC patients) who were recruited between March 2011 and December 2012. A logistic regression model was constructed using a training cohort (n = 353) and validated using an independent cohort (n = 181). The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the diagnostic accuracy. RESULTS: We determined that a panel based on the expression of uc001ncr and AX800134 accurately diagnosed HBV positive HCC (AUC values of 0.9494 and 0.9491 for the training and validation cohorts, respectively). The diagnostic performance of the panel remained high in patients with AFP<=400 ng/ml (AUC values of 0.9371 and 0.9527 for the training and validation cohorts, respectively). The panel also diagnosed early HCC (AUC values of 0.9450 and 0.9564 for the training and validation cohorts, respectively). CONCLUSION: Our results indicated that the serum expression of uc001ncr and AX800134 has potential as novel potential biomarker for the diagnosis of HCC, especially in patients with AFP<=400 ng/ml or early-stage disease (BCLC 0+A). PMID- 26674526 TI - Interventions to Improve Adherence in Patients with Immune-Mediated Inflammatory Disorders: A Systematic Review. AB - BACKGROUND: In patients with immune-mediated inflammatory disorders, poor adherence to medication is associated with increased healthcare costs, decreased patient satisfaction, reduced quality of life and unfavorable treatment outcomes. OBJECTIVE: To determine the impact of different interventions on medication adherence in patients with immune-mediated inflammatory disorders. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and Cochrane Library. STUDY ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included studies were clinical trials and observational studies in adult outpatients treated for psoriasis, Crohn's disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or multiple sclerosis. STUDY APPRAISAL AND SYNTHESIS METHODS: Intervention approaches were classified into four categories: educational, behavioral, cognitive behavioral, and multicomponent interventions. The risk of bias/study limitations of each study was assessed using the GRADE system. RESULTS: Fifteen studies (14 clinical trials and one observational study) met eligibility criteria and enrolled a total of 1958 patients. Forty percent of the studies (6/15) was conducted in patients with inflammatory bowel disease, half (7/15) in rheumatoid arthritis patients, one in psoriasis patients and one in multiple sclerosis patients. Seven out of 15 interventions were classified as multicomponent, four as educational, two as behavioral and two as cognitive behavioral. Nine studies, of which five were multicomponent interventions, had no serious limitations according to GRADE criteria. Nine out of 15 interventions showed an improvement of adherence: three multicomponent interventions in inflammatory bowel disease; one intervention of each category in rheumatoid arthritis; one multicomponent in psoriasis and one multicomponent in multiple sclerosis. CONCLUSION: The assessment of interventions designed for increasing medication adherence in IMID is rare in the literature and their methodological quality may be improved in upcoming studies. Nonetheless, multicomponent interventions showed the strongest evidence for promoting adherence in patients with IMID. PMID- 26674527 TI - Successful use of laparoscopic myomectomy to remove a giant uterine myoma: a case report. AB - INTRODUCTION: Uterine leiomyomas are the most common benign neoplasms of the female reproductive tract. Myomectomy is the preferred surgical treatment in reproductive-aged women who desire to retain their fertility. The use of a laparoscopic approach for large myomas is still controversial, although there are several compelling reasons for its use. The laparoscopic removal of giant uterine myomas is rare, and only a few cases have been published in the literature. CASE PRESENTATION: We report the case of a 33-year-old white woman who was referred to our clinic with progressive abdominal distension. An ultrasonic examination revealed a markedly enlarged uterus containing a 17 cm uterine myoma. Laparoscopic myomectomy was selected as the treatment option. The laparoscopy confirmed the 17 cm fundal intramural myoma. The myoma was totally enucleated and removed without disturbing her endometrial cavity. The myometrial defect was repaired with a continuous suture using the V-loc suture in two layers. The entire myoma was removed using a tissue morcellator. The total weight of the myoma removed was 2005g, and the operation lasted for 140 minutes. Her postoperative course was unremarkable. CONCLUSIONS: Laparoscopic myomectomy offers many advantages compared with abdominal myomectomy. Although the use of a laparoscopic approach to treat very large myomas is controversial and technically demanding, we successfully performed a laparoscopic myomectomy in a patient with a giant myoma. This case confirms the efficiency, reliability, and safety of a minimally invasive surgical approach to treating a giant uterine myoma. Laparoscopic myomectomy can be performed by experienced surgeons regardless of the size of the myoma. PMID- 26674528 TI - Tenacibaculum ascidiaceicola sp. nov., isolated from the golden sea squirt Halocynthia aurantium. AB - A Gram-stain-negative, non-flagellated, non-spore-forming bacterial strain motile by gliding, designated RSS1-6T, was isolated from a golden sea squirt Halocynthia aurantium and its taxonomic position was investigated by using a polyphasic approach. Strain RSS1-6T grew optimally at 30-37 degrees C and in the presence of 1.0-4.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain RSS1-6T fell within the clade comprising species of the genus Tenacibaculum, clustering with the type strains of Tenacibaculum discolor, Tenacibaculum litoreum and Tenacibaculum gallaicum with which it exhibited 16S rRNA gene sequence similarity values of 98.5-99.5 %. Strain RSS1-6T contained MK 6 as the predominant menaquinone and iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) as the major fatty acids. The major polar lipids of strain RSS1-6T were phosphatidylethanolamine, two unidentified lipids, one unidentified aminophospholipid and one unidentified glycolipid. The DNA G+C content was 32.5 mol% and the mean DNA-DNA relatedness values with the type strains of T. discolor, T. litoreum and T. gallaicum were 17.3-25.2 %. The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain RSS1-6T is separated from other recognized species of the genus Tenacibaculum. On the basis of the data presented, strain RSS1-6T is considered to represent a novel species of the genus Tenacibaculum, for which the name Tenacibaculum ascidiaceicola sp. nov. is proposed. The type strain is RSS1-6T ( = KCTC 42702T = NBRC 111225T). PMID- 26674529 TI - The organizational dynamics enabling patient portal impacts upon organizational performance and patient health: a qualitative study of Kaiser Permanente. AB - BACKGROUND: Patient portals may lead to enhanced disease management, health plan retention, changes in channel utilization, and lower environmental waste. However, despite growing research on patient portals and their effects, our understanding of the organizational dynamics that explain how effects come about is limited. METHODS: This paper uses qualitative methods to advance our understanding of the organizational dynamics that influence the impact of a patient portal on organizational performance and patient health. The study setting is Kaiser Permanente, the world's largest not-for-profit integrated delivery system, which has been using a portal for over ten years. We interviewed eighteen physician leaders and executives particularly knowledgeable about the portal to learn about how they believe the patient portal works and what organizational factors affect its workings. Our analytical framework centered on two research questions. (1) How does the patient portal impact care delivery to produce the documented effects?; and (2) What are the important organizational factors that influence the patient portal's development? RESULTS: We identify five ways in which the patient portal may impact care delivery to produce reported effects. First, the portal's ability to ease access to services improves some patients' satisfaction as well as changes the way patients seek care. Second, the transparency and activation of information enable some patients to better manage their care. Third, care management may also be improved through augmented patient-physician interaction. This augmented interaction may also increase the 'stickiness' of some patients to their providers. Forth, a similar effect may be triggered by a closer connection between Kaiser Permanente and patients, which may reduce the likelihood that patients will switch health plans. Finally, the portal may induce efficiencies in physician workflow and administrative tasks, stimulating certain operational savings and deeper involvement of patients in medical decisions. Moreover, our analysis illuminated seven organizational factors of particular importance to the portal's development -and thereby ability to impact care delivery: alignment with financial incentives, synergy with existing IT infrastructure and operations, physician-led governance, inclusive decision making and knowledge sharing, regional flexibility to implementation, continuous innovation, and emphasis on patient-centered design. CONCLUSIONS: These findings show how organizational dynamics enable the patient portal to affect care delivery by summoning organization-wide support for and use of a portal that meets patient needs. PMID- 26674530 TI - Prediction of Spontaneous Protein Deamidation from Sequence-Derived Secondary Structure and Intrinsic Disorder. AB - Asparagine residues in proteins undergo spontaneous deamidation, a post translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis". PMID- 26674531 TI - Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and -2. AB - BACKGROUND: Metastasis is the major cause of death in breast cancers. MMPs play a key role in tumor microenvironment that facilitates metastasis. The existing researches suggest that the high expression of gelatinase A and B (MMP2 and MMP9) promote the metastasis of breast cancer. Therefore, gelatinase inhibitor can effectively suppress tumor metastasis. However, at present, there is no dramatically effective gelatinase inhibitor against breast cancer. METHODS: We screened gelatinase inhibitor among Chinese herbal medicine by molecular docking technology; investigated the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line in response to the treatment with the screened inhibitor by wound assay, invasion assay and gelatin zymography; then further examined the effects of inhibitor on allograft mammary tumors of mice by immunohistochemistry. RESULTS: We successfully screened an Chinese herbal medicine-Plantamajoside(PMS)-which can reduce the gelatinase activity of MMP9 and MMP2. In vitro, PMS can inhibit the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line by decreasing MMP9 and MMP2 activity. In vivo, oral administration of PMS to the mice bearing 4T1 cells induced tumors resulted in significant reduction in allograft tumor volume and weights, significant decrease in microvascular density and significant lower lung metastasis rate. CONCLUSIONS: Our results indicate that as a promising anti-cancer agent, PMS may inhibit growth and metastasis of breast cancer by inhibiting the activity of MMP9 and MMP2. PMID- 26674532 TI - Near-Total Bone Flap Resorption following Autologous Bone Cranioplasty in a Child. PMID- 26674533 TI - Mitochondrial Haplotype Diversity in Zambian Lions: Bridging a Gap in the Biogeography of an Iconic Species. AB - Analysis of DNA sequence diversity at the 12S to 16S mitochondrial genes of 165 African lions (Panthera leo) from five main areas in Zambia has uncovered haplotypes which link Southern Africa with East Africa. Phylogenetic analysis suggests Zambia may serve as a bridge connecting the lion populations in southern Africa to eastern Africa, supporting earlier hypotheses that eastern-southern Africa may represent the evolutionary cradle for the species. Overall gene diversity throughout the Zambian lion population was 0.7319 +/- 0.0174 with eight haplotypes found; three haplotypes previously described and the remaining five novel. The addition of these five novel haplotypes, so far only found within Zambia, nearly doubles the number of haplotypes previously reported for any given geographic location of wild lions. However, based on an AMOVA analysis of these haplotypes, there is little to no matrilineal gene flow (Fst = 0.47) when the eastern and western regions of Zambia are considered as two regional sub populations. Crossover haplotypes (H9, H11, and Z1) appear in both populations as rare in one but common in the other. This pattern is a possible result of the lion mating system in which predominately males disperse, as all individuals with crossover haplotypes were male. The determination and characterization of lion sub-populations, such as done in this study for Zambia, represent a higher resolution of knowledge regarding both the genetic health and connectivity of lion populations, which can serve to inform conservation and management of this iconic species. PMID- 26674534 TI - Targeting MET Receptor in Rhabdomyosarcoma: Rationale and Progress. AB - MET is a tyrosine kinase receptor, which binds hepatocyte growth factor (HGF). It regulates many physiological processes and participates in the regulation of proliferation, differentiation and motility of various cells. It plays an important role in embryogenesis as well as in adult life. Aberrations within the regulatory pathways activated by MET can be one of the causes of tumor development. Recently novel important functions of MET signaling in tumor development have been described, such as maintenance of cancer stem cells or importance of endosomal localization of MET. Moreover, MET is considered as one of the important factors responsible for development of rhabdomyosarcoma (RMS), a soft tissue sarcoma related to myogenic lineage. Its origin remains debatable but it is suggested that it derives from defect in differentiation of the satellite cells or of the mesenchymal stem cells. In RMS MET downregulation induces differentiation of tumor cells and in consequence, metastatic potential of RMS cells is diminished. Therefore, blocking of MET may be clinically useful in novel differentiationbased therapies of RMS in future. PMID- 26674535 TI - Quantifying the Heterogeneity of Chemical Structures in Complex Charged Polymers through the Dispersity of Their Distributions of Electrophoretic Mobilities or of Compositions. AB - The complexity of synthetic and natural polymers used in industrial and medical applications is expanding; thus, it becomes increasingly important to improve and develop methods for their molecular characterization. Free-solution capillary electrophoresis is a robust technique for the separation and characterization of both natural and synthetic complex charged polymers. In the case of polyelectrolytes, free-solution capillary electrophoresis is in the "critical conditions" (CE-CC): it allows their separation by factors other than molar mass for molar masses typically higher than 20000 g/mol. This method is thus complementary to size-exclusion chromatography (SEC). SEC is widely used to determine molar mass distributions and their dispersities. Utilizing CE-CC, an analogous calculation of dispersity based on the distributions of electrophoretic mobilities was derived and the heterogeneity of composition or branching in different polysaccharides or synthetic polymers was obtained in a number of experimental cases. Calculations are based on a ratio of moments and could therefore be compared to simulations of polymerization processes, in analogy to the work performed on molar mass distributions. Among four possible types of dispersity, the most precise values were obtained with the calculation analogous with the dispersity of molar mass distribution Mw/Mn. In addition, the dispersity value allows conclusions based on a single value: the closer the dispersity is to 1, the more homogeneous the polymer is in terms of composition or branching. This approach allows the analysis of dispersity of important molecular attributes of polymers other than molar mass and aims at improving the overall molecular characterization of both synthetic and natural polymers. The dispersity can also be monitored online while performing a chemical reaction within the CE instrument. PMID- 26674537 TI - Ovarian Leiomyoma Along with Uterine Leiomyomata: A Common Tumour at an Uncommon Site. AB - Ovarian leiomyoma is one of the rarest benign tumours of the ovary, mostly seen in women of reproductive age group. Here we report a case of ovarian leiomyoma as an incidental finding in a patient of 38-year-old woman with uterine leiomyomata. Peroperatively, her left ovary appeared bulky & she underwent total abdominal hysterectomy with left salpingo-oophorectomy. Macroscopically, in addition to uterine leiomyomata, a grey-white solid mass was seen entirely within the ovary without any capsular breach. Microscopically, the ovarian mass resembled its uterine counterpart without any evidence of atypia or necrosis. Masson trichrome stain & immunohistochemistry for desmin positivity confirmed the smooth muscle origin of the tumour cells. Despite its rarity, ovarian leiomyoma has to be considered as one of the differential diagnosis of ovarian spindle cell tumours. In difficult cases, immunohistochemistry aids the diagnosis. PMID- 26674536 TI - Access To Care And Affordability Have Improved Following Affordable Care Act Implementation; Problems Remain. AB - There is growing evidence that millions of adults have gained insurance coverage under the Affordable Care Act, but less is known about how access to and affordability of care may be changing. This study used data from the Health Reform Monitoring Survey to describe changes in access and affordability for nonelderly adults from September 2013, just prior to the first open enrollment period in the Marketplace, to March 2015, after the end of the second open enrollment period. Overall, we found strong improvements in access to care for all nonelderly adults and across income and state Medicaid expansion groups. We also found improvements in the affordability of care for all adults and for low- and moderate-income adults. Despite this progress, there were still large gaps in access and affordability in March 2015, particularly for low-income adults. PMID- 26674538 TI - Editorial Comment on: I. Sudol-Szopinska, E. Kontny, K. Zaniewicz-Kaniewska, M. Prohorec-Sobieszek, F. Saied and W. Maslinski Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I and I. Sudol-Szopinska, P. Hrycaj and M. Prohorec-Sobieszek Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part II. PMID- 26674539 TI - Major Placenta Previa: Rate, Maternal and Neonatal Outcomes Experience at a Tertiary Maternity Hospital, Sohag, Egypt: A Prospective Study. AB - INTRODUCTION: Major degree placenta is a serious health issue and is associated with high fetal-maternal morbidity and mortality. Literature from developing countries is scant. AIM: To determine the prevalence and maternal and neonatal outcomes among women with major placenta previa (PP). MATERIALS AND METHODS: A prospective descriptive study of 52 singleton pregnancies with PP was evaluated in this study. The study was conducted at Sohag University Hospital, Egypt from January through June 2014. Outcome measures, including the prevalence of PP, maternal and neonatal outcomes, and case-fatality rate. RESULTS: The total number of deliveries performed during the study period was 3841, of them, 52 cases were placenta previa. Thus, the prevalence of PP was 1.3%. The mean of previous cesarean scars was 2.2+/-1.4. Of women with PP, 26.4% (n=14) had placenta accreta. In total, 15.1% (n=8) of women underwent an obstetric hysterectomy. From the total no. of babies, 13.2% (n=7) were delivered fresh stillborn babies. Of the surviving babies (n=45), 20% (n=9) required admission to NICU. The frequencies of bowel and bladder injuries were 3.8% (n=2) and 13.2% (n=7) respectively. There was no maternal death in this study. CONCLUSION: The rate of PP is comparable to previous studies, however, the rate of placenta accreta is high. Also, there are high rates of neonatal mortality and intraoperative complications which can be explained by accreta. The study highlights the need to revise maternity and child health services. PMID- 26674540 TI - Large intracranial volume accelerates conversion to dementia in males and APOE4 non-carriers with mild cognitive impairment. AB - BACKGROUND: It is unclear how brain reserve interacts with gender and apolipoprotein E4 (APOE4) genotype, and how this influences the progression of Alzheimer's disease (AD). The association between intracranial volume (ICV) and progression to AD in subjects with mild cognitive impairment (MCI), and differences according to gender and APOE4 genotype, was investigated. METHODS: Data from subjects initially diagnosed with MCI and at least two visits were downloaded from the ADNI database. Those who progressed to AD were defined as converters. The longitudinal influence of ICV was determined by survival analysis. The time of conversion from MCI to AD was set as a fiducial point, as all converters would be at a similar disease stage then, and longitudinal trajectories of brain atrophy and cognitive decline around that point were compared using linear mixed models. RESULTS: Large ICV increased the risk of conversion to AD in males (HR: 4.24, 95% confidence interval (CI): 1.17-15.40) and APOE4 non-carriers (HR: 10.00, 95% CI: 1.34-74.53), but not in females or APOE4 carriers. Cognitive decline and brain atrophy progressed at a faster rate in males with large ICV than in those with small ICV during the two years before and after the time of conversion. CONCLUSIONS: Large ICV increased the risk of conversion to AD in males and APOE4 non-carriers with MCI. This may be due to its influence on disease trajectory, which shortens the duration of the MCI stage. A longitudinal model of progression trajectory is proposed. PMID- 26674542 TI - Vertical Ge/Si Core/Shell Nanowire Junctionless Transistor. AB - Vertical junctionless transistors with a gate-all-around (GAA) structure based on Ge/Si core/shell nanowires epitaxially grown and integrated on a ?111? Si substrate were fabricated and analyzed. Because of efficient gate coupling in the nanowire-GAA transistor structure and the high density one-dimensional hole gas formed in the Ge nanowire core, excellent P-type transistor behaviors with Ion of 750 MUA/MUm were obtained at a moderate gate length of 544 nm with minimal short channel effects. The experimental data can be quantitatively modeled by a GAA junctionless transistor model with few fitting parameters, suggesting the nanowire transistors can be fabricated reliably without introducing additional factors that can degrade device performance. Devices with different gate lengths were readily obtained by tuning the thickness of an etching mask film. Analysis of the histogram of different devices yielded a single dominate peak in device parameter distribution, indicating excellent uniformity and high confidence of single nanowire operation. Using two vertical nanowire junctionless transistors, a PMOS-logic inverter with near rail-to-rail output voltage was demonstrated, and device matching in the logic can be conveniently obtained by controlling the number of nanowires employed in different devices rather than modifying device geometry. These studies show that junctionless transistors based on vertical Ge/Si core/shell nanowires can be fabricated in a controlled fashion with excellent performance and may be used in future hybrid, high-performance circuits where bottom-up grown nanowire devices with different functionalities can be directly integrated with an existing Si platform. PMID- 26674544 TI - Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure. AB - BACKGROUND: We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats. METHODS: Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated with levosimendan (3 mg.kg.d) 3 days before surgery [n = 10, prevention (PREV)], 3 weeks after surgery [n = 10, reversal (REV)] or vehicle (n = 10, VEH). Sham operated rats received vehicle (n = 16, SHAM). Right ventricular function was evaluated 7 weeks after surgery by echocardiography, magnetic resonance imaging, pressure-volume relations, gross anatomy, and histology. RESULTS: PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index (CI) without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs. PREV 281 +/- 17 vs. 362 +/- 34 mL.min.kg, P <= 0.05, RVEF: VEH vs. PREV 57 +/- 2% vs. 68 +/- 3%, P <= 0.01) to values similar to SHAM (CI: 345 +/- 21 mL.min.kg, RVEF: 71 +/- 2%). RV contractility was improved in the REV group measured by preload recruitable stroke work (VEH vs. REV 39 +/- 3 vs. 66 +/- 10 mmHg P <= 0.05). CONCLUSIONS: Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure. PMID- 26674545 TI - Fifty Years of Chemical Reaction Dynamics. PMID- 26674543 TI - The pan-class I phosphatidyl-inositol-3 kinase inhibitor NVP-BKM120 demonstrates anti-leukemic activity in acute myeloid leukemia. AB - Aberrant activation of the PI3K/Akt/mTOR pathway is a common feature of acute myeloid leukemia (AML) patients contributing to chemoresistance, disease progression and unfavourable outcome. Therefore, inhibition of this pathway may represent a potential therapeutic approach in AML. The aim of this study was to evaluate the pre-clinical activity of NVP-BKM120 (BKM120), a selective pan-class I PI3K inhibitor, on AML cell lines and primary samples. Our results demonstrate that BKM120 abrogates the activity of the PI3K/Akt/mTOR signaling, promoting cell growth arrest and significant apoptosis in a dose- and time-dependent manner in AML cells but not in the normal counterpart. BKM120-induced cytotoxicity is associated with a profound modulation of metabolic behaviour in both cell lines and primary samples. In addition, BKM120 synergizes with the glycolitic inhibitor dichloroacetate enhancing apoptosis induction at lower doses. Finally, in vivo administration of BKM120 to a xenotransplant mouse model of AML significantly inhibited leukemia progression and improved the overall survival of treated mice. Taken together, our findings indicate that BKM120, alone or in combination with other drugs, has a significant anti-leukemic activity supporting its clinical development as a novel therapeutic agent in AML. PMID- 26674546 TI - Histopathological Spectrum of Tumor and ?Tumor-like Lesions of the Paratestis in a ?Tertiary Care Hospital. AB - OBJECTIVES: Tumors and tumor-like lesions (TLL) of the paratesticular region are rare. Very few studies depicting the spectrum of lesions of this location are available in the literature. Malignant neoplasms arising in the paratesticular region represent only 7.0% of malignant tumors presenting as a scrotal mass. TLL and benign tumors are of great interest, because of their topography they can simulate a neoplasm in the paratesticular structures. We sought to study the incidence, nature, pattern, clinical, immune, and histopathological characteristics of tumors and TLL of the paratestis. METHODS: In this six-year study, records of the cases were reviewed and the histopathology slides were reassessed. Blocks were retrieved and stained immunohistochemically for relevant markers. RESULTS: A total of 47 cases of tumor and TLL of the paratestis were diagnosed over a six-year period. The patients ranged from one to 76 years old and most presented with a scrotal mass. Of these, seven (14.9%) were benign. Lipoma was the most common benign tumor. One case each of adenomatoid tumor, scrotal hemangioma, solitary fibrous tumor, and papillary cyst adenoma were reported. The TLL (70.2%) comprised of 17 cases of epididymal cyst, seven cases of tuberculous epididymitis, four cases of filarial epididymitis, two cases each of non-specific granulomatous epididymitis and fibromatous periorchitis, and one case of mesothelial cyst. Seven malignant tumors (14.9%) were diagnosed all of which were sarcomas. All seven were primary to the paratesticular region. The most common malignant tumor was embryonal rhabdomyosarcoma. One case each of malignant mesothelioma, malignant fibrous histiocytoma, atypical lipomatous tumor/well-differentiated liposarcoma, and myxoid liposarcoma were identified. CONCLUSION: Neoplasms of the paratesticular region affect patients of all ages, with potentially life-threatening sequelae. Awareness of the entire spectrum and meticulous histopathological examination and immunohistochemical studies are of prime importance in the diagnosis of the various lesions as these influence the mode of therapy and subsequent prognosis of the patient. PMID- 26674547 TI - The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex. AB - The basal fungus Allomyces macrogynus (A. macrogynus) produces motile male gametes displaying well-studied chemotaxis toward their female counterparts. This chemotaxis is driven by sirenin, a sexual pheromone released by the female gametes. The pheromone evokes a large calcium influx in the motile gametes, which could proceed through the cation channel of sperm (CatSper) complex. Herein, we report the total synthesis of sirenin in 10 steps and 8% overall yield and show that the synthetic pheromone activates the CatSper channel complex, indicated by a concentration-dependent increase in intracellular calcium in human sperm. Sirenin activation of the CatSper channel was confirmed using whole-cell patch clamp electrophysiology with human sperm. Based on this proficient synthetic route and confirmed activation of CatSper, analogues of sirenin can be designed as blockers of the CatSper channel that could provide male contraceptive agents. PMID- 26674548 TI - Bipolar membrane electrodialysis for generation of hydrochloric acid and ammonia from simulated ammonium chloride wastewater. AB - Simulated ammonium chloride wastewater was treated by a lab-scale bipolar membrane electrodialysis for the generation of HCl and NH3.H2O and desalination. The influence of initial concentration of NH4Cl, current density, salt solution volume, initial concentration of acid and base and membrane stack structure on the yields of HCl and NH3.H2O was investigated. The current efficiency and energy consumption were also examined under different conditions. The results showed that, at the current density of 48 mA/cm(2), the highest concentration of HCl and NH3.H2O with initial concentration of 110 g/L NH4Cl was 57.67 g/L and 45.85 g/L, respectively. Higher initial concentration of NH4Cl was favor to reduce unit energy consumption and increase current efficiency of the BMED system. The membrane stack voltage of BMED increased quickly under constant current when the concentration of NH4Cl contained in the solution of salt compartment was depleted below the "inflection point concentration" about 8000 mg/L. It means that the concentration of NH4Cl below 8000 mg/L was no longer suitable for BMED because of higher energy consumption. The HCl and NH3.H2O concentration increased more quickly following the increase of current density. When increasing the volume of NH4Cl, the concentration of HCl and NH3.H2O also increased. The high initial concentration of acid and base could improve the final concentration of them, while the growth rate was decreased. Compared with the BMED system with three compartments, the growth rate of HCl concentration with the two compartments was higher and its unit energy consumption was lower. It meant that the performance of the BMED system could be improved by optimizing operation conditions. The application feasibility of the generation of HCl and NH3.H2O and desalination of ammonium chloride wastewater by BMED was proved. PMID- 26674549 TI - Membrane-based processes for wastewater nutrient recovery: Technology, challenges, and future direction. AB - Wastewater nutrient recovery holds promise for more sustainable water and agricultural industries. We critically review three emerging membrane processes - forward osmosis (FO), membrane distillation (MD) and electrodialysis (ED) - that can advance wastewater nutrient recovery. Challenges associated with wastewater nutrient recovery were identified. The advantages and challenges of applying FO, MD, and ED technologies to wastewater nutrient recovery are discussed, and directions for future research and development are identified. Emphasis is given to exploration of the unique mass transfer properties of these membrane processes in the context of wastewater nutrient recovery. We highlight that hybridising these membrane processes with existing nutrient precipitation process will lead to better management of and more diverse pathways for near complete nutrient recovery in wastewater treatment facilities. PMID- 26674551 TI - The Chemistry of Cold: Mechanisms of Torpor Regulation in the Siberian Hamster. AB - Siberian hamsters use spontaneous daily torpor, a state of hypometabolism and hypothermia, to save energy during winter. Multiple neuroendocrine signals set the scene for spontaneous torpor to occur, and several brain areas have been identified as potential sites for torpor regulation. Here, we summarize the known mechanisms of a fascinating physiological state in the Siberian hamster. PMID- 26674550 TI - Pulsatility of Hypothalamo-Pituitary Hormones: A Challenge in Quantification. AB - Neuroendocrine systems control many of the most fundamental physiological processes, e.g., reproduction, growth, adaptations to stress, and metabolism. Each such system involves the hypothalamus, the pituitary, and a specific target gland or organ. In the quantification of the interactions among these components, biostatistical modeling has played an important role. In the present article, five key challenges to an understanding of the interactions of these systems are illustrated and discussed critically. PMID- 26674552 TI - The Role of Hydrogen Sulfide in Evolution and the Evolution of Hydrogen Sulfide in Metabolism and Signaling. AB - The chemical versatility of sulfur and its abundance in the prebiotic Earth as reduced sulfide (H2S) implicate this molecule in the origin of life 3.8 billion years ago and also as a major source of energy in the first seven-eighths of evolution. The tremendous increase in ambient oxygen ~ 600 million years ago brought an end to H2S as an energy source, and H2S-dependent animals either became extinct, retreated to isolated sulfide niches, or adapted. The first 3 billion years of molecular tinkering were not lost, however, and much of this biochemical armamentarium easily adapted to an oxic environment where it contributes to metabolism and signaling even in humans. This review examines the role of H2S in evolution and the evolution of H2S metabolism and signaling. PMID- 26674554 TI - In Reply to the Letter to the Editor regarding Analysis of Changing Paradigms of Management in 179 Patients with Spinal Tuberculosis During a 12-Year Period and Proposal of a New Management Algorithm. PMID- 26674553 TI - Factors Related to Non-Referral of Patients with Presumptive Pulmonary TB to Designated Microscopy Centers (DMCs) by Registered Private Practitioners in Urban Areas of Punjab, India. AB - BACKGROUND: Early diagnosis and proper treatment under RNTCP guidelines, forms the mainstay of management of a TB patient. A large proportion of patients with presumptive tuberculosis (TB) visit a Private Practitioner (PP) in the first place. Studies have shown that PPs rely more on X-rays and other diagnostic tools rather than referring the patient to the nearest Designated Microscopy Centre (DMC) for sputum microscopy. AIM: The present study was planned to look in to factors responsible for non-referral of patients with presumptive pulmonary TB to the DMCs for diagnosis by PPs. MATERIALS AND METHODS: Present study was a case control study conducted over a period of one year among registered PPs in urban areas of Punjab. The study was carried out in five major cities which have approximately half of the urban population of Punjab. Forty three Private Practitioners per city for referral group and 43 matched PPs for non-referral group were selected. RESULTS: Knowledge regarding RNTCP was low in both the referral (38.1%) as well as non-referral (25.6%) group of PPs. Allopathic doctors had significantly higher knowledge regarding TB as compared to ayurvedic and homeopathy doctors, and Registered Medical Practitioners (RMP). Both the knowledge of PPs regarding nearest DMC as well as perception about accessibility of the nearest DMC for the patients were found to be significantly higher in the referral group. Only 15.3% of practitioners in the non-referral group said that they had been contacted by RNTCP staff. CONCLUSION: The main factors responsible for non-referral of pulmonary TB suspects to DMCs for diagnosis in the present study included low knowledge regarding RNTCP, lack of awareness regarding place and accessibility of nearest DMC, and inadequate sensitization of PPs by the RNTCP staff. PMID- 26674555 TI - Pathotypes of Bacterial Spot Pathogen Infecting Capsicum Peppers in Korea. AB - Sixty-seven isolates of bacterial spot pathogen (Xanthomonas spp.) collected from six provinces of Korea were tested for the identification of their pathotypes and determination of their distribution throughout Korea in an effort to genetically manage the disease. Near isogenic lines of Early Calwonder (Capsicum annuum) pepper plants carrying Bs1 , Bs2 and Bs3 , and PI235047 (C. pubescens) were used as differential hosts. Race P1 was found to be predominant, followed by race P7, and races P3 and P8 were also observed. This is the first report of races P7 and P8 in Korea. The races P7 and P8 were differentiated from the former races P1 and P3, respectively, on the basis of their ability to elicit hypersensitive reactions to PI235047. PMID- 26674556 TI - Quantitative expression of regulatory and differentiation-related genes in the key steps of human hematopoiesis: The LeukoStage Database. AB - Differentiation during hematopoiesis leads to the generation of many cell types with specific functions. At various stages of maturation, the cells may change pathologically, leading to diseases including acute leukemias (ALs). Expression levels of regulatory molecules (such as the IKZF, GATA, HOX, FOX, NOTCH and CEBP families, as well as SPI-1/PU1 and PAX5) and lineage-specific molecules (including CD2, CD14, CD79A, and BLNK) may be compared between pathological and physiological cells. Although the key steps of differentiation are known, the available databases focus mainly on fully differentiated cells as a reference. Precursor cells may be a more appropriate reference point for diseases that evolve at immature stages. Therefore, we developed a quantitative real-time polymerase chain reaction (qPCR) array to investigate 90 genes that are characteristic of the lymphoid or myeloid lineages and/or are thought to be involved in their regulation. Using this array, sorted cells of granulocytic, monocytic, T and B lineages were analyzed. For each of these lineages, 3-5 differentiation stages were selected (17 stages total), and cells were sorted from 3 different donors per stage. The qPCR results were compared to similarly processed AL cells of lymphoblastic (n=18) or myeloid (n=6) origins and biphenotypic AL cells of B cell origin with myeloid involvement (n=5). Molecules characteristic of each lineage were found. In addition, cells of a newly discovered switching lymphoblastic AL (swALL) were sorted at various phases during the supposed transdifferentiation from an immature B cell to a monocytic phenotype. As demonstrated previously, gene expression changed along with the immunophenotype. The qPCR data are publicly available in the LeukoStage Database in which gene expression in malignant and non-malignant cells of different lineages can be explored graphically and differentially expressed genes can be identified. In addition, the LeukoStage Database can aid the functional analyses of next-generation sequencing data. PMID- 26674557 TI - Fertility preservation in pre-pubertal girls with cancer: the role of ovarian tissue cryopreservation. AB - With the increasing numbers of survivors of cancer in young people, future fertility and ovarian function are important considerations that should be discussed before treatment commences. Some young people, by nature of the treatment they will receive, are at high risk of premature ovarian insufficiency and infertility. For them, ovarian tissue cryopreservation (OTC) is one approach to fertility preservation that remains both invasive and for young patients experimental. There are important ethical and consent issues that need to be explored and accepted before OTC can be considered established in children with cancer. In this review we have discussed a framework for patient selection which has been shown to be effective in identifying those patients at high risk of premature ovarian insufficiency and who can be offered OTC safely. PMID- 26674558 TI - Detection of intratubular germ cell neoplasia in nonobstructive azoospermia: is it relevant? PMID- 26674559 TI - Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims data. AB - OBJECTIVE: To determine the incidence of chronic medical conditions of men with infertility. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Subjects contained within the Truven Health MarketScan claims database from 2001 to 2009. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The development of chronic medical conditions including hypertension, diabetes, hyperlipidemia, renal disease, pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder. RESULT(S): In all, 13,027 men diagnosed with male factor infertility were identified with an additional 23,860 receiving only fertility testing. The average age was 33.1 years for men diagnosed with infertility and 32.8 years for men receiving testing alone. After adjusting for confounding factors, men diagnosed with male factor infertility had a higher risk of developing diabetes (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10-1.53), ischemic heart disease (HR 1.48, 95% CI 1.19-1.84), alcohol abuse (HR 1.48, 95% CI 1.07-2.05), and drug abuse (1.67, 95% CI 1.06-2.63) compared with men who only received infertility testing. Similar patterns were identified when comparing those with male factor infertility to vasectomized men. The association between male factor infertility and later health outcomes were strongest for men with longer follow up. CONCLUSION(S): In this cohort of patients in a national insurance database, men diagnosed with male factor infertility had a significantly higher risk of adverse health outcomes in the years after an infertility evaluation. These findings suggest the overall importance of men's reproductive health and warrant additional investigation to understand the association and identify interventions to improve outcomes for these patients. PMID- 26674560 TI - Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb. AB - The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the "elevator technique". All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the "Journal of Ultrasonography". PMID- 26674561 TI - Plasmablastic lymphoma is treatable in the HAART era. A 10 year retrospective by the AIDS Malignancy Consortium. PMID- 26674562 TI - CaM Kinases: From Memories to Addiction. AB - Drug addiction is a major psychiatric disorder with a neurobiological basis that is still insufficiently understood. Initially, non-addicted, controlled drug consumption and drug instrumentalization are established. They comprise highly systematic behaviours acquired by learning and the establishment of drug memories. Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are important Ca(2+) sensors translating glutamatergic activation into synaptic plasticity during learning and memory formation. Here we review the role of CaMKs in the establishment of drug-related behaviours in animal models and in humans. Converging evidence now shows that CaMKs are a crucial mechanism of how addictive drugs induce synaptic plasticity and establish various types of drug memories. Thereby, CaMKs are not only molecular relays for glutamatergic activity but they also directly control dopaminergic and serotonergic activity in the mesolimbic reward system. They can now be considered as major molecular pathways translating normal memory formation into establishment of drug memories and possibly transition to drug addiction. PMID- 26674563 TI - No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy. AB - Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI) resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents. PMID- 26674564 TI - Key Signaling Events for Committing Mouse Pluripotent Stem Cells to the Germline Fate. AB - The process of germline development carries genetic information and preparatory totipotency across generations. The last decade has witnessed remarkable successes in the generation of germline cells from mouse pluripotent stem cells, especially induced germline cells with the capacity for producing viable offspring, suggesting clinical applications of induced germline cells in humans. However, to date, the culture systems for germline induction with accurate sex specific meiosis and epigenetic reprogramming have not been well-established. In this study, we primarily focus on the mouse model to discuss key signaling events for germline induction. We review mechanisms of competent regulators on primordial germ cell induction and discuss current achievements and difficulties in inducing sex-specific germline development. Furthermore, we review the developmental identities of mouse embryonic stem cells and epiblast stem cells under certain defined culture conditions as it relates to the differentiation process of becoming germline cells. PMID- 26674565 TI - ADDITIONS AND CORRECTIONS. Effects of Synchronous and Asynchronous Embryo Transfer on Postnatal Development, Adult Health, and Behavior in Mice. PMID- 26674566 TI - The Transcription Factor Interferon Regulatory Factor-1 (IRF1) Plays a Key Role in the Terminal Effector Pathways of Human Preterm Labor. AB - Preterm birth is the largest single cause of neonatal death and morbidity. By activating cytokine- and Toll-like receptor (TLR)-signaling pathways, infection and/or inflammation are strongly associated with preterm delivery. Interferon regulatory factor-1 (IRF1) is an important regulator of the inflammatory response. The aims of this study were to establish the effect of 1) labor on IRF1 expression in human fetal membranes and myometrium, 2) prolabor mediators on IRF1 expression and activity, and 3) IRF1 small interfering RNA on the expression of prolabor mediators. IRF1 expression was higher in fetal membranes and myometrium after spontaneous term labor and in preterm fetal membranes with infection. The proinflammatory cytokine IL1B, the bacterial product fsl-1, and viral analog polyinosinic:polycytidylic acid (poly [I:C]) significantly increased IRF1 mRNA expression and transcriptional activity in human primary myometrial cells. In addition, IL1B increased IRF1 activity in primary amnion cells. IRF1 silencing in myometrial cells decreased IL1B-, fsl-1-, and poly (I:C)-induced cytokine (IL6, TNF, IL1B) and chemokine (CXCL8, CCL2) mRNA expression and IL6, CXCL8, and CCL2 release. IL1B-, fsl-1-, and poly (I:C)-induced PTGS2 mRNA expression and IL1B induced prostaglandin release was also decreased by IRF1 silencing. In conclusion, IRF1 upregulation in fetal membranes and myometrium after term labor indicates a proinflammatory role for IRF1 in human parturition. IRF1 is involved in TLR- and cytokine-mediated signaling in human myometrium. These data provide new insights into the mechanisms associated with inflammation- and infection associated preterm birth. IRF1 inhibitors as therapeutics for the management of spontaneous preterm birth warrants further investigation. PMID- 26674567 TI - Comparative Proteomic, Physiological, Morphological, and Biochemical Analyses Reveal the Characteristics of the Diploid Spermatozoa of Allotetraploid Hybrids of Red Crucian Carp (Carassius auratus) and Common Carp (Cyprinus carpio). AB - The generation of diploid spermatozoa is essential for the continuity of tetraploid lineages. The DNA content of diploid spermatozoa from allotetraploid hybrids of red crucian carp and common carp was nearly twice as great as that of haploid spermatozoa from common carp, and the durations of rapid and slow progressive motility were longer. We performed comparative proteomic analyses to measure variations in protein composition between diploid and haploid spermatozoa. Using two-dimensional electrophoresis followed by liquid chromatography tandem mass spectrometry, 21 protein spots that changed in abundance were analyzed. As the common carp and the allotetraploid hybrids are not fully sequenced organisms, we identified proteins by Mascot searching against the National Center for Biotechnology Information non-redundant (NR) protein database for the zebrafish (Danio rerio), and verified them against predicted homologous proteins derived from transcriptomes of the testis. Twenty protein spots were identified successfully, belonging to four gene ontogeny categories: cytoskeleton, energy metabolism, the ubiquitin-proteasome system, and other functions, indicating that these might be associated with the variation in diploid spermatozoa. This categorization of variations in protein composition in diploid spermatozoa will provide new perspectives on male polyploidy. Moreover, our approach indicates that transcriptome data are useful for proteomic analyses in organisms lacking full protein sequences. PMID- 26674568 TI - Enthesopathies and enthesitis. Part 1. Etiopathogenesis. AB - The pathologies of tendon and ligament attachments are called enthesopathies. One of its types is enthesitis which is a characteristic sign of peripheral spondyloarthropathy. Clinical diagnosis of enthesitis is based on rather non specific clinical signs and results of laboratory tests. Imaging examinations are highly promising. Numerous publications prove that enthesitis can be differentiated from other enthesopathic processes in an ultrasound examination or magnetic resonance imaging. However, some reports indicate the lack of histological criteria, specific immunological changes and features in imaging examinations that would allow the clinical diagnosis of enthesitis to be confirmed. The first part of the publication presents theories on the etiopathogenesis of enthesopathies: inflammatory, mechanical, autoimmune, genetic and associated with the synovio-entheseal complex, as well as theories on the formation of enthesophytes: inflammatory, molecular and mechanical. The second part of the paper is a review of the state-of-the-art on the ability of imaging examinations to diagnose enthesitis. It indicates that none of the criteria of inflammation used in imaging medicine is specific for this pathology. As enthesitis may be the only symptom of early spondyloarthropathy (particularly in patients with absent HLA-B27 receptor), the lack of its unambiguous picture in ultrasound and magnetic resonance scans prompts the search for other signs characteristic of this disease and more specific markers in imaging in order to establish diagnosis as early as possible. PMID- 26674569 TI - Genetic polymorphisms (Pro197Leu of Gpx1, +35A/C of SOD1, -262C/T of CAT), the level of antioxidant proteins (GPx1, SOD1, CAT) and the risk of distal symmetric polyneuropathy in Polish patients with type 2 diabetes mellitus. AB - PURPOSE: Oxidative stress and impaired anti-oxidant defense are regarded as contributory factors for distal symmetric polyneuropathy (DSPN). The purpose of the study was to evaluate the plasma level of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) and the association between polymorphic variants in genes encoding for GPx1, SOD, CAT and the risk of DSPN in T2DM patients. MATERIAL/METHODS: We included 401 individuals: 110 T2DM patients with DSPN, 135 T2DM patients without DSPN, and 156 control subjects with normoglycemia, and without DSPN. We employed RFPL-PCR to genotype polymorphic variants Pro197Leu of Gpx1, +35A/C of SOD1, -262C/T of CAT and ELISA tests to measure plasma level of SOD1, GPx1 and CAT. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. RESULTS: There was a significant decrease in the level of GPx1 (p<0.05), SOD1 (p<0.05) in T2DM patients with DSPN compared to healthy subjects. T2DM patients without DSPN showed a statistically lower serum level of GPX1 (p<0.05) than healthy subjects. SOD 1 and CAT levels were lower in T2DM patients with DSPN compared to T2DM patients without DSPN (p<0.05). The genetic analysis revealed the lack of association between examined polymorphic variants and the risk of DSPN. CONCLUSIONS: The examined polymorphic variants are not associated with DSPN in Polish T2DM patients. The obtained results suggest that disturbances in antioxidant defense system may play significant role in the development and progression of DSPN. PMID- 26674570 TI - Serum adiponectin level in obstructive sleep apnea: Relation of adiponectin to obesity and long-term continuous positive airway pressure therapy. AB - PURPOSE: The study aimed to determine the effect of OSA and obesity on the plasma levels of adiponectin and the long-term effect of CPAP on its plasma levels and obesity parameters. MATERIAL/METHODS: A prospective observational study included 159 newly diagnosed OSA patients. The cohort was divided into CPAP treated (n=82) and control group (n=77). Both groups were examined at the beginning and a year later. The CPAP-treated patients were additionally tested after a month of therapy. The examinations included Epworth Sleepiness Scale questionnaire, anthropometric and polysomnographic measurements, and blood serum tests. Changes in the studied parameters of OSA, obesity, and adiponectin obtained at the beginning and after follow-up period were compared in each group. RESULTS: In CPAP group, all studied OSA parameters improved already after a month of CPAP therapy. Contrarily, obesity parameters (except of neck and waist circumference) remained unchanged after CPAP therapy. Serum adiponectin levels dropped during CPAP therapy. In the control group, both obesity and OSA parameters did not show changes. The only exceptions were deteriorated mean SpO2 and decreased hip circumference. Adiponectin remained unchanged in this group. In neither group, the Spearman correlation analyses showed any association of serum adiponectin levels with obesity or OSA parameters, except of mean SpO2. CONCLUSIONS: Only correlation found was between adiponectin and mean SpO2. Although CPAP therapy improves all OSA parameters, it did not change most obesity parameters. Additionally in the CPAP group, there was a significant drop in adiponectin levels, suggesting its protective role in this group of patients. PMID- 26674571 TI - TPMT and ITPA genetic variants in Lithuanian inflammatory bowel disease patients: Prevalence and azathioprine-related side effects. AB - PURPOSE: Inter-individual thiopurine metabolism variability can influence treatment outcomes in inflammatory bowel disease (IBD) patients. Genetic polymorphisms in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) were linked with toxicity of azathioprine (AZA). The aim of the study was to investigate frequencies of TPMT and ITPA polymorphisms in Lithuanian IBD patients and analyze their association with AZA-related adverse events. MATERIALS/METHODS: Polymorphisms in TPMT (TPMT*2,*3B,*3C,*3A) and ITPA (rs1127354, rs7270101) genes were determined using PCR-RFLP and TaqMan((r)) genotyping assays. 551 consecutive Lithuanian IBD patients were genotyped. The use of AZA and its side effects were assessed retrospectively according to hospital medical records. RESULTS: Frequencies of TPMT*3A, TPMT*3B and TPMT*3C alleles were 3.1%, 0.5% and 0.1%, respectively. TPMT*2 genetic variant was not detected in the study group. The distribution of minor alleles for ITPA rs1127354 and rs7270101 polymorphisms was 9.9% and 10.5%, respectively. AZA was prescribed in 82 patients and it provoked myelotoxicity in 11%, hepatotoxicity in 6.1%, dyspepsia in 6.1%, and pancreatitis in 3.6% of cases. Among patients who had AZA related myelotoxicity, 11.1% were TPMT compound heterozygous, 44.4% had heterozygous genotype (P<0.01). Frequencies of ITPA minor alleles were similar among the patients with and without AZA-related side effects. CONCLUSION: Frequencies of TPMT and ITPA variant alleles in Lithuanian IBD group were similar to those observed in the Northern-Eastern Europe Caucasian populations. Polymorphisms in TPMT might be associated with myelotoxicity and leukopenia in AZA treated patients, while ITPA variant alleles appear not to be linked with treatment-related side effects. PMID- 26674572 TI - Sex hormone effects on autonomic mechanisms of thermoregulation in humans. AB - Autonomic mechanisms are fundamental to human physiological thermoregulation, and female reproductive hormones have substantial influences on several aspects of these mechanisms. Of these, the best recognized are the thermoregulatory responses that occur at menopause (hot flushes) and the changes in body temperature within the menstrual cycle which may help couples predict ovulation. Our goal in this brief review is to summarize current knowledge regarding the influences of reproductive hormones on autonomic mechanisms in human thermoregulation. In general, estrogens tend to promote lower body temperatures via augmentation of heat dissipation responses, whereas progesterone tends to promote higher body temperatures. Recent evidence suggests specific influences of estrogens on central autonomic nuclei involved in control of skin blood flow and sweating. Estrogens also augment vasodilation by direct effects on peripheral blood vessels. Influences of progesterone are less well understood, but include both centrally regulated changes in thermoregulatory set-point as well as and peripheral effects, including augmented vasoconstriction in the skin. We conclude with a brief discussion of thermoregulatory adjustments associated with changing hormone levels during menopause, pregnancy and polycystic ovary syndrome. PMID- 26674583 TI - Concern regarding quality and quality of muscle. PMID- 26674573 TI - Comprehensive Application of Time-of-flight Secondary Ion Mass Spectrometry (TOF SIMS) for Ionic Imaging and Bio-energetic Analysis of Club Drug-induced Cognitive Deficiency. AB - Excessive exposure to club drug (GHB) would cause cognitive dysfunction in which impaired hippocampal Ca(2+)-mediated neuroplasticity may correlate with this deficiency. However, the potential changes of in vivo Ca(2+) together with molecular machinery engaged in GHB-induced cognitive dysfunction has never been reported. This study aims to determine these changes in bio-energetic level through ionic imaging, spectrometric, biochemical, morphological, as well as behavioral approaches. Adolescent rats subjected to GHB were processed for TOF SIMS, immunohistochemistry, biochemical assay, together with Morris water maze to detect the ionic, molecular, neurochemical, and behavioral changes of GHB-induced cognitive dysfunction, respectively. Extent of oxidative stress and bio energetics were assessed by levels of lipid peroxidation, Na(+)/K(+) ATPase, cytochrome oxidase, and [(14)C]-2-deoxyglucose activity. Results indicated that in GHB intoxicated rats, decreased Ca(2+) imaging and reduced NMDAR1, nNOS, and p CREB reactivities were detected in hippocampus. Depressed Ca(2+)-mediated signaling corresponded well with intense oxidative stress, diminished Na(+)/K(+) ATPase, reduced COX, and decreased 2-DG activity, which all contributes to the development of cognitive deficiency. As impaired Ca(2+)-mediated signaling and oxidative stress significantly contribute to GHB-induced cognitive dysfunction, delivering agent(s) that improves hippocampal bio-energetics may thus serve as a promising strategy to counteract the club drug-induced cognitive dysfunction emerging in our society nowadays. PMID- 26674584 TI - Characterization of environmental Vibrio cholerae serogroups O1 and O139 in the Pearl River Estuary, China. AB - Toxigenic isolates of Vibrio cholerae serogroups O1 and O139 from aquatic reservoirs are a key source for recurrent epidemics of cholera in human populations. However, we do not have an optimal understanding of the microbiology of the strains within these reservoirs, particularly outside of the time periods when there are active cholera cases in the surrounding community. The main objective of the present study was to identify and characterize V. cholerae O1 and O139 in the Pearl River Estuary at a time when active disease was not being identified, despite prior occurrence of epidemic cholera in the region. Water samples were collected at 24 sites in the research area at monthly intervals between 2007 and 2010, and screened for the presence of V. cholerae O1 and O139. All isolates were screened for the presence of ctxAB, ompW, toxR, and tcpA genes. Multilocus variable number tandem repeat analysis (MLVA) was used to assess possible relationships among strains. The results show that Vibrio cholerae O1 or O139 was isolated, on average, from 6.7% of the sites screened at each time point. All V. cholerae O1 and O139 isolates were ctxAB negative, and 37% were positive for tcpA. Isolation was most common in the oldest, most urbanized district compared with other districts, and was associated with lower pH. Despite year-to-year variability in isolation rates, there was no evidence of seasonality. MLVA of 27 selected isolates showed evidence of high genetic diversity, with no evidence of clustering by year or geographic location. In this region where cholera has been epidemic in the past, there is evidence of environmental persistence of V. cholerae O1 and O139 strains. However, environmental strains were consistently nontoxigenic, with a high level of genetic diversity; their role as current or future agents of human disease remains uncertain. PMID- 26674585 TI - Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter. AB - BACKGROUND: Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients. N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients. We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC. METHODS: A total of 368 patients with COPD were recruited and the polymorphisms of their HO-1 gene promoter were classified into three subclasses according to the number of (GT)n repeats, as previously reported: class S (<27 (GT)n repeats), class M (27-32 (GT)n repeats), and class L (>32 (GT)n repeats). These subjects were then classified as L+ group (with the L allele: L/L, L/M, L/S) and L- group (without the L allele: M/M, M/S, S/S). All the patients were allocated to standard therapy plus NAC 600 mg bid over a 1-year period and were observed over that year. RESULTS: The L- group saw improvements in forced expiratory volume in 1 second (FEV1) (from 1.44+/-0.37 to 1.58+/-0.38, P=0.04) and FEV1% predicted (from 56.6+/-19.2 to 59.7+/-17.2, P=0.03). No improvement was found in forced vital capacity of each group and the decline of forced vital capacity in both of the groups was not statistical significant. The number of yearly COPD exacerbations of the L- group was 1.5+/-0.66 which was lower than the 2.1+/-0.53 of the L+ group (P<0.01). For the changes of St George's Respiratory Questionnaire (SGRQ) score, only the activity score of the L- group was more significant than that of the L+ group (P=0.02). The improvement of the outcome of 6-minute walking distance test in L- group (from 290.1+/-44.9 meters to 309.7+/ 46.9 m) was higher than that in the L+ group (from 289.7+/-46.2 m to 300.3+/-44.2 m) (P=0.03). CONCLUSION: A 600 mg bid oral NAC treatment for 1-year on COPD patients without the L allele can improve the FEV1, FEV1% predicted, the SGRQ activity score, and the result of 6-minute walking distance test, and the exacerbation rate of the L allele carrier in COPD patients is much higher than in the COPD patients without the L allele. PMID- 26674586 TI - Pathogenic ability and saline stress tolerance of two Fusarium isolates from Odontesthes bonariensis eggs. AB - BACKGROUND: Several fungal species represent a potential risk to embryos of Odontesthes bonariensis (Cuvier and Valenciennes, 1835), a euryhaline freshwater fish that lives in the Pampean inland waters and has potential economic relevance. AIMS: To identify two fungi isolated from O. bonariensis eggs exposed to saline conditions and to characterize their pathogenicity and tolerance to sodium chloride solutions. METHODS: The isolates were identified by morphological features, and a preliminar phylogenetic analysis using sequences of translation elongation factor 1-alpha (EF-1alpha) and calmodulin (CAM) was performed. Koch's postulates were tested to identify the causative agent of fungal infection. The influence of NaCl on the fungal growth was evaluated in in vitro assays. RESULTS: The isolates LPSC 1001 and 1002 were identified as representatives of the genus Fusarium, and belonging to the Fusarium incarnatum-Fusarium equiseti species complex (FIESC) and the Fusarium solani species complex (FSSC), respectively. Histological observations on eggs exposed in vitro to both isolates in infectivity assays confirmed the ability of the fungal isolates to penetrate to egg's chorionic membrane, leading to the death of embryos. Increasing NaCl concentration in the culture medium reduced the growth of the isolates LPSC 1001 and 1002, being completely inhibited at 160 and 120g/l NaCl respectively. CONCLUSIONS: The isolates LPSC 1001 (FIESC) and 1002 (FSSC) were identified as fungal pathogens to O. bonariensis eggs. The use of NaCl solutions as antifungal treatment was not effective to control the infection with these strains. PMID- 26674587 TI - Neural Substrates of Emotion-Processing Abnormalities in Borderline Personality Disorder. PMID- 26674588 TI - A More Global Look at Altered Neural Structure and Resting-State Function in Borderline Personality Disorder. PMID- 26674589 TI - Coronary artery fistula between single right coronary artery and right pulmonary artery: a case report and literature review. AB - BACKGROUND: Coronary artery fistula and single coronary artery are two different rare congenital anomalies. The cases with co-existed the two anomalies are more rare. To the best of our knowledge with literature review, the coronary artery fistula between single right coronary artery and right pulmonary artery has not been previously reported. CASE PRESENTATION: In the present article, we report a Chinese patient (a 8-month-old male) who presented cyanosis when cried and heart murmur. The cardiac angiography confirmed coronary artery fistula between single coronary artery arising from the right aortic sinus and right pulmonary artery. Furthermore, the right pulmonary artery was interrupted with main pulmonary artery and the pulmonary blood supplied by single right coronary artery. Following the surgical procedure, the anomalous fistula vessel was cut and sutured. The right pulmonary artery was reconstructed to connect with main pulmonary artery. The patient had an uneventful postoperative course and discharged. Then we reviewed the related literature with Medline and Pubmed databases for further details. CONCLUSION: We believe our patient is the very particular case about coronary artery fistula combined with single coronary artery, and it is first reported with our literature review. As other coronary anomalies, coronary or aortic root angiography is the gold standard method for the diagnosis. Furthermore, early surgery is an optimal treatment in our case. PMID- 26674590 TI - Efficacy of Endoscopically Created Bypass Anastomosis in Treatment of Afferent Limb Syndrome: A Single-Center Study. AB - Afferent limb syndrome is a postoperative complication of gastrointestinal surgery, resulting from obstruction of a biliary-enteric limb. Surgery has been the cornerstone of treatment for this condition, but advances in endoscopic and percutaneous techniques could offer less-invasive options. Creation of an internal endoscopic anastomosis between the obstructed afferent limb and an adjacent gastrointestinal lumen can relieve symptoms and might provide a long term solution. We report the efficacy of endoscopic treatment of afferent limb syndrome using lumen-apposing self-expandable metal stents to create 3 types of enteric anastomoses: a jejunojejunostomy, 2 gastrojejunostomies, and a duodenuojejunostomy in patients who developed afferent limb obstruction following a resection for pancreaticobiliary cancer. PMID- 26674591 TI - Esophageal Cancer: Current Options for Therapeutic Management. AB - BACKGROUND: Esophageal cancer (EC) is the eighth most common cancer worldwide. A worldwide-established consensus on therapeutic pathways for EC is still missing. Debate exists on whether neoadjuvant and adjuvant treatment regimens improve the prognosis and which surgical approach reaches objective benefits. SUMMARY: This article discusses the appropriate option of the current different curative treatments in patients with EC, including surgical treatment and adjuvant therapy. KEY MESSAGE: To maximize survival and quality of life and also decrease postoperative complications, the present recommended therapeutic management of EC should be individualized multidisciplinary team approaches according to patients' staging and physiologic reserve. PRACTICAL IMPLICATIONS: The aim of this article is to provide a decision support and also a discussion based on clinical therapeutic strategy in order to characterize the beneficial approach which reaches an optimal balance between radical resection, postoperative outcome and long-term survival of EC. PMID- 26674592 TI - Current Status of Hepatic Arterial Infusion Chemotherapy. AB - BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) is frequently used to treat advanced hepatocellular carcinoma (HCC) in Asian countries. However, there is a lack of evidence supporting the use of HAIC. SUMMARY: Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic measures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-labelled, randomized clinical trial of HAIC in advanced HCC is currently in progress. Optimization of HCC treatment protocols and regimens is also required. KEY MESSAGE: We think that both HAIC and sorafenib are effective treatments for advanced HCC, and this review presents evidence supporting this contention. PMID- 26674593 TI - Crystal phase competition by addition of a second metal cation in solid solution metal-organic frameworks. AB - Herein we report a synthetic study focused on the preparation of solid-solution metal-organic frameworks, MOFs, with the use of two kinds of linkers. In particular, we have explored the system composed by zinc, cobalt, 1,2,4-triazole and 4,4'-hexafluoroisopropylidenebisbenzoic acid (H2hfipbb). During this study, four new MOFs have been isolated, denoted TMPF-88 [M3(hfipbb)2(triazole)2(H2O)], TMPF-90 [M2(triazole)3(OCH2CH3)], TMPF-91 [M2(hfipbb)(triazole)2(H2O)] and TMPF 95 [M5(hfipbb)4(triazole)2(H2O)] (TMPF = transition metal polymeric framework, M = Zn, Co, or mixture of them). The study demonstrates that the addition of a second metal element during the MOF synthesis has a major effect in the formation of new phases, even at very high Zn/Co metal ratios. Furthermore, we show that during the MOF formation reaction, there is a competition among different crystal phases, where kinetically favoured phases of various compositions crystallize in short reaction times, precluding the formation of the pure solid-solution phases of other energetically more stable MOFs. PMID- 26674594 TI - Clinical Profile and Chemotherapy Response in Children with Hodgkin Lymphoma at a Tertiary Care Centre. AB - INTRODUCTION: Optimal treatment strategy in children with advance stage Hodgkin Lymphoma (HL) still remains controversial. AIM: To evaluate the clinical profile and the efficacy of chemotherapy (CT) as a treatment modality in paediatric HL. MATERIAL AND METHODS: Retrospective case record evaluation of paediatric HL cases over 5 years (October 2005 to October 2010) period. RESULTS: Thirty five cases (31 boys) with a median age of eight years were studied. 24 cases were <10-year old, and 23 had late stage disease (stage III to IV). B-symptoms were present in 60%, bulky mediastinal disease in 25.7%, and spleen involvement in 60% cases. None had bone marrow involvement. Most common histological type was nodular sclerosis (28.6%). Most cases received ABVD/COPP or ABVD regimen. Two cases needed BEACOPP due to progressive disease, and 4 needed low-dose involved field radiotherapy (RT). At a mean (SD) extended event-free follow-up of 42.7(+/-17.1) months, four cases relapsed (one was lost to follow-up, and three were treated with chemotherapy and low-dose involved field RT). None died due to the disease. CONCLUSION: Present study found systemic CT alone to be an effective therapy in childhood Hodgkin lymphoma. However, a small sample in present study limits the generalisability of these findings. The findings needs to be replicated in larger population, preferably randomized clinical trials, before any firm conclusion can be made. PMID- 26674595 TI - The feature selection bias problem in relation to high-dimensional gene data. AB - OBJECTIVE: Feature selection is a technique widely used in data mining. The aim is to select the best subset of features relevant to the problem being considered. In this paper, we consider feature selection for the classification of gene datasets. Gene data is usually composed of just a few dozen objects described by thousands of features. For this kind of data, it is easy to find a model that fits the learning data. However, it is not easy to find one that will simultaneously evaluate new data equally well as learning data. This overfitting issue is well known as regards classification and regression, but it also applies to feature selection. METHODS AND MATERIALS: We address this problem and investigate its importance in an empirical study of four feature selection methods applied to seven high-dimensional gene datasets. We chose datasets that are well studied in the literature-colon cancer, leukemia and breast cancer. All the datasets are characterized by a significant number of features and the presence of exactly two decision classes. The feature selection methods used are ReliefF, minimum redundancy maximum relevance, support vector machine-recursive feature elimination and relaxed linear separability. RESULTS: Our main result reveals the existence of positive feature selection bias in all 28 experiments (7 datasets and 4 feature selection methods). Bias was calculated as the difference between validation and test accuracies and ranges from 2.6% to as much as 41.67%. The validation accuracy (biased accuracy) was calculated on the same dataset on which the feature selection was performed. The test accuracy was calculated for data that was not used for feature selection (by so called external cross validation). CONCLUSIONS: This work provides evidence that using the same dataset for feature selection and learning is not appropriate. We recommend using cross validation for feature selection in order to reduce selection bias. PMID- 26674596 TI - Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment. AB - The relative cardiovascular (CV) safety of oral anticoagulants continues to be debated, and in particular concerns for risk of myocardial infarction (MI) have been raised. We analyzed the risk of MI in patients treated long term with oral anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or pulmonary embolism using a network meta-analysis (NMA). METHODS: Randomized, phase 3 trials comparing novel anticoagulants to VKA were searched. Information on study design and clinical outcomes was extracted. The primary end-point of the analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple treatment analysis was performed using fixed-effect and random-effects modeling. RESULTS: Twelve trials including 100,524 randomized patients were analyzed. The odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban, apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59 CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for dabigatran. CONCLUSIONS: There is a considerable heterogeneity regarding CV safety among oral anticoagulants. Differences in risk of MI may influence the choice of treatment. Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting the concerns regarding its CV safety. PMID- 26674597 TI - Using Unlicensed Health Coaches to Improve Care for Insured Patients with Diabetes and Hypertension: Patient and Physician Perspectives on Recruitment and Uptake. AB - Health coach programs using low-cost unlicensed providers have largely targeted uninsured or underserved populations, raising questions about uptake and effectiveness for insured patients. This observational study evaluated the referral process, uptake, and effectiveness of a health coach program for patients with diabetes and/or hypertension at a multispecialty clinic. Data included appointment observations; interviews with patients, physicians, and health coaches; patient and physician characteristics; and measures of utilization and clinical outcomes. Out of 1313 eligible patients, 308 (23.5%) were referred over a 12-month period and 169 (54.9%) had at least 1 health coach appointment. Although the health coach program did not change patients' biometrics, physicians and patients reported improved care processes and reduced physician workload. Barriers to enrollment included variability in physician referral practices, patient willingness, and scheduling difficulties. Modifications to physician and health coach workflow are needed to determine the program's true effectiveness. PMID- 26674598 TI - Mental Health and Medical Health Disparities in 5135 Transgender Veterans Receiving Healthcare in the Veterans Health Administration: A Case-Control Study. AB - PURPOSE: There are no large controlled studies of health disparities in transgender (TG) or gender dysphoric patients. The Veterans Health Administration (VHA) is the largest healthcare system in the United States and was an early adopter of electronic health records. We sought to determine whether medical and/or mental health disparities exist in VHA for clinically diagnosed TG veterans compared to matched veterans without a clinical diagnosis consistent with TG status. METHODS: Using four ICD-9-CM codes consistent with TG identification, a cohort of 5135 TG veterans treated in VHA between 1996 and 2013 was identified. Veterans without one of these diagnoses were matched 1:3 in a case-control design to determine if medical and/or mental health disparities exist in the TG veteran population. RESULTS: In 2013, the prevalence of TG veterans with a qualifying clinical diagnosis was 58/100,000 patients. Statistically significant disparities were present in the TG cohort for all 10 mental health conditions examined, including depression, suicidality, serious mental illnesses, and post-traumatic stress disorder. TG Veterans were more likely to have been homeless, to have reported sexual trauma while on active duty, and to have been incarcerated. Significant disparities in the prevalence of medical diagnoses for TG veterans were also detected for 16/17 diagnoses examined, with HIV disease representing the largest disparity between groups. CONCLUSION: This is the first study to examine a large cohort of clinically diagnosed TG patients for psychiatric and medical health outcome disparities using longitudinal, retrospective medical chart data with a matched control group. TG veterans were found to have global disparities in psychiatric and medical diagnoses compared to matched non-TG veterans. These findings have significant implications for policy, healthcare screening, and service delivery in VHA and potentially other healthcare systems. PMID- 26674599 TI - HSP90 Inhibitor Geldanamycin as a Radiation Response Modificator in Human Blood Cells. AB - Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone, involved in the folding, assembly, stabilization and activation of numerous proteins with unrelated amino acid sequences and functions. Geldanamycin (GA), a natural benzoquinone, can inhibit the chaperone activity of Hsp90. It has been shown that GA can produce superoxide anions and increase the intracellular oxidative stress, which, in addition to the direct inhibition of Hsp90, might also contribute to the modifying effects of the inhibitor on the early response in human mononuclear cells exposed to ionizing radiation. The present study shows that GA antagonizes the radiation-induced suppression on MnSOD and catalase, key enzymes of the radical scavenging systems. By significantly up-regulating catalase levels over the entire range of doses from 0.5 to 4 Gy, the inhibitor of Hsp90 exerted adaptive protection and modified the early radiation response of the human blood cells. PMID- 26674600 TI - 2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and monitoring of treatment of vesicoureteral reflux in children - can it replace voiding cystourethrography? AB - INTRODUCTION: Vesicoureteral reflux appears in 20-50% of pediatric patients with recurrent urinary tract infections. The most common method of diagnosing this disease is voiding cystourethrography. However, contemporary pediatric radiology does not favor this method due to exposure to X-radiation. AIM: The aim of this study was to assess the usefulness of 2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and treatment monitoring of vesicoureteral reflux in children and the possibility of using contrast-enhanced voiding urosonography to replace voiding cystourethrography. MATERIAL AND METHODS: Voiding cystourethrography and contrast-enhanced voiding urosonography were conducted in 80 pediatric patients in order to assess sensitivity, specificity, positive and negative predictive values as well as the number of vesicoureteral refluxes detected by each of the two methods. The second stage of the study involved performing voiding urosonography in an extended protocol in 58 children in order to determine the usefulness of three-dimensional (3D/4D) examinations in the assessment of vesicoureteral reflux and the ability to assess the urethra. RESULTS: The concordance between the two methods was 86.95%. The sensitivity of voiding urosonography was 84.51%, specificity - 90.99%, positive predictive value - 85.71% and negative predictive value - 90.17%. A 3D/4D assessment of the urinary bladder and transperineal 2D morphological assessment of the urethra were possible in all patients (100%). Assessment of the urethra during micturition with the use of 2D/3D/4D techniques was possible in all patients in whom voiding was elicited (95.83%), and 3D/4D assessment of vesicoureteral reflux was possible in all patients with reflux (100%). Although the application of 3D/4D techniques allowed accurate specification of the grade of reflux in all cases (100%), it appeared particularly useful in differentiating between grades II and III (70.97%). CONCLUSIONS: Contrast-enhanced voiding urosonography allows the diagnosis and monitoring of treatment of vesicoureteral reflux in pediatric patients as well as assessment of the urethra in both girls and boys. The method is characterized by high sensitivity and specificity. Moreover, it is safe, relatively inexpensive and can replace voiding cystourethrography. PMID- 26674601 TI - Lgr5 expression is a valuable prognostic factor for colorectal cancer: evidence from a meta-analysis. AB - BACKGROUND: Lgr5 has recently been identified as a reliable biomarker of cancer stem cells (CSCs) in colorectal cancer (CRC); however, its prognostic value is still controversial. METHODS: We searched PubMed, Web of Science, and Wanfang databases with identical strategies to retrieve articles. We evaluated the impact of Lgr5 expression on survival of CRC patients through meta-analysis. RESULTS: A total of 12 studies comprising 2600 patients revealed that Lgr5 overexpression was negatively associated with overall survival (OS) (HR=1.73, 95% CI: 1.28-2.33; P=0.00) and disease free survival (DFS) (HR=2.89, 95% CI: 1.89-4.44; P=0.000) in CRC patients. Subgroup analysis suggested that Lgr5 overexpression was significantly associated with worse OS in subgroups with IHC as the method of Lgr5 assessment (HR=2.01, 95% CI: 1.39-2.89; P=0.001), patients from Asia (HR=1.81, 95% CI: 1.27-2.58; P=0.000), and NOS scores greater than 6 (HR=2.12, 95% CI: 1.41-3.19; P=0.000). Furthermore, sensitivity analysis showed that the estimated HR ranged from 1.6 to 1.86 upon excluding one study sequentially from each analysis. In addition, Lgr5 overexpression was significantly associated with deep invasion of CRC (OR=0.39, 95% CI: 0.17-0.87; P=0.002), lymphnode metastasis (OR=0.45, 95% CI: 0.26-0.76; P=0.003), distant metastasis (OR=0.37, 95% CI: 0.22 0.62; P=0.000), and AJCC stage (OR=0.35, 95% CI: 0.15-0.78; P=0.01). However, Lgr5 overexpression was not correlated with tumor grade (OR=0.75 95% CI: 0.37 1.54; P=0.433). CONCLUSIONS: This study shows that Lgr5 can be a valuable and reliable prognostic factor of colorectal cancer progression. PMID- 26674603 TI - The effect of fluorophore incorporation on fluorescence enhancement in colloidal photonic crystals. AB - The significant effect of photonic crystals (PhCs) on fluorophore emission has recently received intense interest. However, so far little attention has been paid on the influence of the fluorophore incorporation method on the performance of PhCs, particularly in practical applications. In this study, rhodamine B is immobilised on polystyrene spheres using a diffusion-swelling method, which are self-assembled into three-dimensional colloidal photonic crystal films. This immobilization method has resulted in 230-fold fluorescence enhancement compared to control films, the greatest fluorescence enhancement of RhB immobilised on monolithic colloidal photonic crystals compared to other immobilization methods such as infiltration and electrostatic charge-facilitated dye attachment on the particle surface. We further demonstrate the stability of dye attachment and the relationship between fluorescence intensity enhancement and the pseudo bandgap position relative to a fluorophore fluorescence peak. PMID- 26674602 TI - Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus. AB - Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID- 26674604 TI - Point-of-care ultrasonography during rescue operations on board a Polish Medical Air Rescue helicopter. AB - Point-of-care ultrasound examination has been increasingly widely used in pre hospital care. The use of ultrasound in rescue medicine allows for a quick differential diagnosis, identification of the most important medical emergencies and immediate introduction of targeted treatment. Performing and interpreting a pre-hospital ultrasound examination can improve the accuracy of diagnosis and thus reduce mortality. The authors' own experiences are presented in this paper, which consist in using a portable, hand-held ultrasound apparatus during rescue operations on board a Polish Medical Air Rescue helicopter. The possibility of using an ultrasound apparatus during helicopter rescue service allows for a full professional evaluation of the patient's health condition and enables the patient to be brought to a center with the most appropriate facilities for their condition. PMID- 26674605 TI - Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption. AB - Drug absorption is a complex process involving dissolution and precipitation, along with other kinetic processes. The purpose of this work was to (1) establish an in vitro methodology to study dissolution and precipitation in early stages of drug development where low compound consumption and high throughput are necessary, (2) develop a mathematical model for a mechanistic explanation of generated in vitro dissolution and precipitation data, and (3) extrapolate in vitro data to in vivo situations using physiologically based models to predict oral drug absorption. Small-scale pH-shift studies were performed in biorelevant media to monitor the precipitation of a set of poorly soluble weak bases. After developing a dissolution-precipitation model from this data, it was integrated into a simplified, physiologically based absorption model to predict clinical pharmacokinetic profiles. The model helped explain the consequences of supersaturation behavior of compounds. The predicted human pharmacokinetic profiles closely aligned with the observed clinical data. In summary, we describe a novel approach combining experimental dissolution/precipitation methodology with a mechanistic model for the prediction of human drug absorption kinetics. The approach unifies the dissolution and precipitation theories and enables accurate predictions of in vivo oral absorption by means of physiologically based modeling. PMID- 26674606 TI - Transient Parotitis After Oesophagogastroduodenoscopy: A Rare Complication. PMID- 26674607 TI - Answer to the question 1 from page 361. PMID- 26674608 TI - Characterization and quantification of histidine degradation in therapeutic protein formulations by size exclusion-hydrophilic interaction two dimensional liquid chromatography with stable-isotope labeling mass spectrometry. AB - Two dimensional liquid chromatography (2D-LC) coupling size exclusion (SEC) and hydrophilic interaction chromatography (HILIC) is demonstrated as a useful tool to study polar excipients, such as histidine and its degradant, in protein formulation samples. The SEC-HILIC setup successfully removed interferences from complex sample matrices and enabled accurate mass measurement of the histidine degradation product, which was then determined to be trans-urocanic acid. Because the SEC effluent is a strong solvent for the second dimension HILIC, experimental parameters needed to be carefully chosen, i.e., small transferring loop, fast gradient at high flow rates for the second dimension gradient, in order to mitigate the solvent mismatch and to ensure good peak shapes for HILIC separations. In addition, the generation of trans-urocanic acid was quantified by single heart-cutting SEC-HILIC 2D-LC combined with stable-isotope labeling mass spectrometry. Compared with existing 2D quantification methods, the proposed approach is fast, insensitive to solvent mismatch between dimensions, and tolerant of small retention time shifts in the first dimension. Finally, the first dimension diode array detector was found to be a potential degradation source for photolabile analytes such as trans-urocanic acid. PMID- 26674610 TI - Locked-In Syndrome: Case Report and Discussion of Decisional Capacity. AB - Locked-in syndrome (LIS) is a rare neurologic disorder rendering an individual quadriplegic and anarthric with preserved self-awareness and normal if not near normal cognition. A lesion to the ventral pons causes the classic form of LIS, and patients can typically interact with their environment with eye/eyelid movements. LIS patients may live for years with preserved quality of life (QoL) and cognitive function, but with severe disability. However, medical providers and family often underestimate the patient's QoL, and choose less aggressive care. Prompt assessment of decisionality in LIS patients is challenging, but it must be done to allow these patients to participate in their care. We present the case of a 54-year-old man with LIS. The medical team recommended comfort measures, but the family advocated involving the patient in goals of care discussions. The patient was determined to be decisional during the acute hospitalization, and he elected for life-prolonging care. This case emphasizes the importance of unbiased shared decision making, but also the importance of utilizing a practical framework to assess the decision-making capacity in these patients. We provide a suggested approach to determining decision-making capacity in similar cases or conditions. PMID- 26674609 TI - Population-Based Quality Indicators for Palliative Care Programs for Cancer Patients in Japan: A Delphi Study. AB - CONTEXT: Cancer control programs in Japan strongly endorse the dissemination of palliative care, and various policy measures have been implemented; however, indicators for evaluating palliative care programs have not been defined. OBJECTIVES: The aim of this study was to develop quality indicators for palliative care programs taking a population-based view to meet the challenge of cancer control in the Japanese population. METHODS: We conducted a modified Delphi survey. The panelists rated a list of indicators over three iterative rounds according to four perspectives: 1) consistency with the policy target, 2) relevance to the problem, 3) clarity of expression, and 4) measurement feasibility. The criterion for adoption of candidate indicators was set at a total mean score of 7 or more. Finally, the most relevant and important indicators were selected; consensus was defined by agreement of panelists at the panel meeting. RESULTS: Among 49 panelists surveyed, 48 (98%), 39 (80%), and 43 (88%) responded over the three rounds, respectively. The 15 indicators were identified from 11 domains: patient-reported quality of life, bereaved family reported quality at the end of life, family care, place of death, bereaved family reported quality of palliative care, specialized palliative care services, opioid utilization, public perceptions about palliative care, palliative care education to primary care providers, specialist palliative care services, and regional palliative care. CONCLUSION: Comprehensive quality indicators for palliative care programs were identified. The indicators are currently being used, and the feasibility of measuring change over time will be examined. It is expected that the indicators will be used effectively in the future. It is important to evaluate outcomes of the program, to improve weaknesses, improve outcomes, and promote the welfare of cancer patients. PMID- 26674611 TI - nCounter((r)) PanCancer Immune Profiling Panel (NanoString Technologies, Inc., Seattle, WA). PMID- 26674612 TI - Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes. AB - Many patients with schizophrenia have poor clinical and social outcomes. Some risk alleles closely related to the onset of schizophrenia have been reported to be associated with their clinical phenotypes, but the direct relationship between genetic vulnerability to schizophrenia and clinical/social outcomes of schizophrenia, as evaluated by both practical clinical scales and 'real-world' function, has not been investigated. We evaluated the clinical and social outcomes of 455 Japanese patients with schizophrenia by severity of illness according to the Clinical Global Impression-Severity Scale (CGI-S) and social outcomes by social adjustment/maladjustment at 5 years after the first visit. We examined whether 46 single nucleotide polymorphisms (SNPs) selected from a Japanese genome-wide association study of susceptibility to schizophrenia were associated with clinical and social outcomes. We also investigated the polygenic risk scores of 46 SNPs. Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. Point estimates of odds ratios showed positive relationships between polygenic risk scores and clinical/social outcomes; however, the results were not statistically significant. Because these results are exploratory, we need to replicate them with a larger sample in a future study. PMID- 26674613 TI - Investigation of the effects of myocardial anisotropy for shear wave elastography using impulsive force and harmonic vibration. AB - The myocardium is known to be an anisotropic medium where the muscle fiber orientation changes through the thickness of the wall. Shear wave elastography methods use propagating waves which are measured by ultrasound or magnetic resonance imaging (MRI) techniques to characterize the mechanical properties of various tissues. Ultrasound- or MR-based methods have been used and the excitation frequency ranges for these various methods cover a large range from 24 500 Hz. Some of the ultrasound-based methods have been shown to be able to estimate the fiber direction. We constructed a model with layers of elastic, transversely isotropic materials that were oriented at different angles to simulate the heart wall in systole and diastole. We investigated the effect of frequency on the wave propagation and the estimation of fiber direction and wave speeds in the different layers of the assembled models. We found that waves propagating at low frequencies such as 30 or 50 Hz showed low sensitivity to the fiber direction but also had substantial bias in estimating the wave speeds in the layers. Using waves with higher frequency content (>200 Hz) allowed for more accurate fiber direction and wave speed estimation. These results have particular relevance for MR- and ultrasound-based elastography applications in the heart. PMID- 26674615 TI - RNA-Seq workflow: gene-level exploratory analysis and differential expression. AB - Here we walk through an end-to-end gene-level RNA-Seq differential expression workflow using Bioconductor packages. We will start from the FASTQ files, show how these were aligned to the reference genome, and prepare a count matrix which tallies the number of RNA-seq reads/fragments within each gene for each sample. We will perform exploratory data analysis (EDA) for quality assessment and to explore the relationship between samples, perform differential gene expression analysis, and visually explore the results. PMID- 26674614 TI - Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue. AB - For many years, it was thought that synovial cells and chondrocytes are the only sources of proinflammatory cytokines and growth factors found in the synovial fluid in patients suffering from osteoarthritis and rheumatoid arthritis. Currently, it is more and more frequently indicated that adipose tissue plays a significant role in the pathogenesis of these diseases as well as that a range of pathological processes that take place in the adipose tissue, synovial membrane and cartilage are interconnected. The adipose tissue is considered a specialized form of the connective tissue containing various types of cells which produce numerous biologically active factors. The latest studies reveal that, similarly to the synovial membrane, articular adipose tissue may take part in the local inflammatory response and affect the metabolism of the cartilage and subchondral osseous tissue. In in vitro conditions, the explants of this tissue obtained from patients suffering from osteoarthritis and rheumatoid arthritis produce similar pro- and anti-inflammatory cytokines to the explants of the synovial membrane. At this stage already, knowledge translates into imaging diagnostics. In radiological images, the shadowing of the periarticular soft tissues may not only reflect synovial membrane pathologies or joint effusion, but may also suggest inflammatory edema of the adipose tissue. On ultrasound examinations, abnormal presentation of the adipose tissue, i.e. increased echogenicity and hyperemia, may indicate its inflammation. Such images have frequently been obtained during ultrasound scanning and have been interpreted as inflammation, edema, hypertrophy or fibrosis of the adipose tissue. At present, when the knowledge concerning pathogenic mechanisms is taken into account, abnormal echogenicity and hyperemia of the adipose tissue may be considered as a proof of its inflammation. In the authors' own practice, the inflammation of the adipose tissue usually accompanies synovitis. However, we also diagnose cases in which the inflammatory process in the joint is no longer active, but abnormal vascularity still persists in the adipose tissue. There are also cases where abnormal adipose tissue is the only sign of inflammation. Therefore, ultrasound examination confirms the existence of the additional site of inflammation, i.e. the adipose tissue which should be evaluated at the stage of initial diagnosis and during follow-up, also in terms of remission. PMID- 26674616 TI - Deciphering the role of interleukin-22 in metabolic alterations. AB - Inflammatory processes and metabolic alterations are supposed to substantially interact. Recently, cumulating reports describe a profound role of interleukin(IL)-22 in this relationship. IL-22 is a particular kind of immune mediator that is produced by certain lymphocyte populations and regulates the function of several tissue cells but not immune cells. So far, IL-22 was known to plays a fundamental role in the elimination of bacterial infections at border surfaces of the body and to protect tissues from damage. This research highlight article arranges the facts regarding the effects of IL-22 in the context of adiposity and metabolic alterations and postulates a new function of the immune system. PMID- 26674617 TI - Standards in neurosonology. Part I. AB - The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler). Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-toleft shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity). PMID- 26674620 TI - [A better understanding in patients with asthma is the cornerstone to improve their overall disease control]. PMID- 26674621 TI - [Severe sepsis in critical care remains a big challenge for physicians]. PMID- 26674619 TI - Results After Anterior Cruciate Ligament Reconstruction in Patients Older Than 40 Years: How Do They Compare With Younger Patients? A Systematic Review and Comparison With Younger Populations. AB - CONTEXT: Anterior cruciate ligament (ACL) reconstruction in older patients is a controversial topic among orthopaedic surgeons. OBJECTIVE: To determine the outcomes, failure, and morbidity associated with ACL reconstruction in patients older than 40 years and to compare it with nonoperative treatment as well as results of ACL reconstruction in a younger patient population. DATA SOURCES: A systematic review of the literature from 1970 to 2015 was conducted utilizing MEDLINE, CINAHL, and the Cochrane Central Register databases using PRISMA guidelines. STUDY SELECTION: Inclusion criteria were studies with longer than 2 year follow-up of primary ACL reconstruction and minimum age of patients older than 40 years, inclusive of any graft type or source and of any concomitant meniscal pathology. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Two independent reviewers collected demographic, preoperative, intraoperative, and postoperative data. RESULTS: Twelve studies with a total of 452 patients were included. The mean patient age was 47.8 years (range, 40-66 years) with a mean follow-up of 53.3 months (minimum, 24 months). Lysholm scores improved from 53.9 to 90.5 in the 11 operative studies. The only nonoperative study reported a mean Lysholm score of 82 after rehabilitation. International Knee Documentation Committee (IKDC) scores of A or B were found in 81%. Tegner activity scores averaged 4.7 preinjury, fell to 2.9 preoperatively, and returned to 4.7 postoperatively. The reported failure rate was 2.3%. There were few complications, and failure rate was similar in younger patients. CONCLUSION: The data confirm that ACL reconstruction can be recommended to patients older than 40 years who wish to maintain an active lifestyle or have symptomatic instability with daily activities. Patient-based outcomes scores were better in the operative studies compared with the single nonoperative study in this patient population. PMID- 26674618 TI - Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells. AB - Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions. PMID- 26674622 TI - [An epidemiological survey on management and insights of asthma in China in 2009 to 2010]. AB - OBJECTIVE: Through the analysis of relevant data of China Asthma and Risk factors Epidemiologic investigation (CARE study), we understand the status quo of management and insights of asthma patients in our country. METHODS: Using multi stage random cluster sampling method, epidemiological survey was performed on the prevalence rate in 8 provinces (cities) of China residents who aged over 14 years from 2009 to 2010. Detailed epidemiological data was collected via face-to-face home visit interview among 2 034 asthmatics who were diagnosed in the last epidemiology survey. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS12.0 software was conducted for statistical analysis and the status of asthma control was investigated. RESULTS: This survey has shown that 22.71% (462/2 034) asthmatics had ever taken a lung functional test in the past year. A total of 294 (14.45%) people had peak flow meters but only 1.62% (33/2 034) regularly used it daily. There were 22.42% (456/2 034) asthmatics aware that bronchial asthma is characterized by chronic airway inflammation. 14.85% (302/2 034) asthmatics understood that the treatment goal of this disease is long-term good control or complete control. This survey has found that 59.64% (1 213/2 034) patients complained that asthma has affected their work, life and entertainment, including 8.90% (181/2 034) asthmatics dependent on instruments in daily life and 4.57% attempting to suicide. This suggested that allergic asthma has seriously decreased the quality of life. CONCLUSION: Therefore it is necessary to educate the asthmatics, guide the patients to the long-term management and standardized therapy and raise the level of disease understanding, thus reducing the burden of disease to society. Gaining better insight of patient's attitude about self-care is critical to the improvement of asthma management. PMID- 26674623 TI - [IgG4-related lung disease:a clinical analysis and literature review]. AB - OBJECTIVE: To summarize the clinical features, diagnosis and treatment experience of IgG4-related lung disease for the sake of improving clinical understanding of this disease and reducing the misdiagnosis and mistreatment rates. METHODS: To analyze the general situation, clinical manifestation, laboratory examination, histopathology, therapy and prognosis of 2 patients with IgG4-related lung disease, who were admitted in the department of respiratory diseases at Changhai Hospital. Publications related to IgG4 lung disease were reviewed. RESULTS: Both patients were male with elevated serum IgG4 level (2.25 g/L and 10 g/L respectively). In one patient, radiologic finding showed solid nodules in the lung with ileocecal involvement. He responded well to glucocorticoid. The other patient's computed tomography of lung demonstrated bronchovascular type. Glucocorticoid therapy was effective to both patients. A total of 69 cases with IgG4-related lung disease were reported worldwide, among whom 39 cases were admitted with chief complaints of respiratory symptoms. However, there were 41 cases suffering extra-pulmonary involvement. Serum IgG4 levels detected in 48 cases were significantly elevated (307-52 500 mg/L). The radiographic pattern of solid nodule type was the most frequent, accounting for 50.7% (35 cases). A total of 31 (44.9%) patients received glucocorticoid therapy with good response and prognosis. CONCLUSION: IgG4-related lung disease is a rare immunological disease lack of specific symptoms. Serum immunological examination, radiographic characteristics and histopathology should be comprehensively considered for diagnosis. Glucocorticoid is so far the most acceptable therapy with good response rate. PMID- 26674624 TI - [The impact of obstructive sleep apnea hypopnea syndrome on glucose metabolism]. AB - OBJECTIVE: To study the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on glucose metabolism and comprehensively analyze its related factors. METHODS: A total of 180 snoring patients were recruited in Sleep Disorder Center of Nanfang Hospital of Southern Medical University between January 2010 to June 2011. There were 140 patients with OSAHS and 40 subjects without OSAHS. All patients underwent both a full polysomnography (PSG) and plasma glucose measure, including fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The FPG, 1-hour post-challenge glucose (1 hPG) and 2-hour post-challenge glucose (2 hPG) were respectively compared in patients with different apnea hypopnea index (AHI), the lowest saturation of pulse oximetry (SpO2) and sleep architecture. RESULTS: The incidence of glucose metabolism disorders was higher in patients with OSAHS than that of those without (diabetes: 21.4% vs 5.0%; prediabetes: 34.3% vs 25.0%). The FPG, 1 hPG and 2 hPG in patients with different AHI was significantly different respectively (all P < 0.01), so as in patients with different lowest oxygen saturation (all P < 0.01). Post-load glucose levels of patients with different AHI were still significantly different after adjustment for neck circumference (1 hPG: P = 0.004; 2 hPG: P = 0.048). FPG, 1 hPG and 2 hPG were associated with AHI (r = 0.167, 0.277, 0.196, all P < 0.05), mean SpO2(r = -0.154, -0.214, -0.182, all P < 0.05) and the lowest SpO2(r = 0.224, -0.231, -0.159, all P < 0.05); While FPG, 1 hPG and 2 hPG were not significantly associated with N1 + N2, N3 and rapid eye movement (REM) sleeps (all P > 0.05). CONCLUSIONS: The risk of glucose metabolism disorders increased with the severity of OSAHS. Compared with fasting glucose, post-load glucose was more affected by OSAHS independent of obesity. Compared with sleep architecture or sleep efficiency, glucose metabolism disorders seem to be associated with hypoxia caused by OSAHS. PMID- 26674625 TI - [The relationship between idiopathic pulmonary fibrosis and gastroesophageal reflux disease]. AB - OBJECTIVE: To study the prevalence and characteristics of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: A total of 48 patients with diffuse parenchymal lung disease (DPLD) including 25 IPF and 23 other DPLD were enrolled from Department of Respiratory Disease in the First Affiliated Hospital of China Medical University. All patients were subjected to 24-hour esophageal pH monitoring. Pulmonary function test and HRCT of lung were performed at the same time. RESULTS: The prevalence of GERD in IPF patients was 64.0%, which was significantly higher than that in other DPLD patients. DeMeester scores were significantly higher in IPF patients than those in non-IPF group [(22.8 +/- 21.5) score vs (15.7 +/- 14.0) score respectively P < 0.05]. Numbers of reflux longer than 5 minutes [(3.8 +/- 4.1) time vs (2.1 +/- 2.1) time respectively) and reflux index (1.8 +/- 1.7 vs 1.3 +/- 1.2) in IPF group were higher than those in non-IPF group, yet without statistical significance. Patients with IPF had significantly higher values of following parameters than those in non-IPF patients including percentage of total reflux time (pH < 4.0) (9.2 +/- 5.1)%, percentage of upright reflux time (8.5 +/- 5.2)%, percentage of supine reflux time (10.8 +/- 10.7)%, numbers of reflux (54.2 +/- 22.7) time, numbers of regurgitation longer than 5 minutes (6.3 +/- 4.2) time, the longest reflux time (14.5 +/- 15.3) min, reflux index 2.5 +/- 1.7 and DeMeester scores (34.9 +/- 20.3) time (P < 0.05). DeMeester score was positively correlated with gastroesophageal reflux diseases questionnaire (GerdQ) score (r = 0.667, P < 0.01). The prevalence of typical GERD sympotoms in the IPF-GERD patients was higher (heartburn 7/16, regurgitation 6/16) than that in IPF patients without GERD (heartburn 2/9, regurgitation 1/9). CONCLUSION: Patients with IPF have a high prevalence of GERD, but usually without typical GERD symptoms. In the hospitals 24-hour esophageal pH monitoring not available, GerdQ can be used to identify GERD in IPF patients. PMID- 26674626 TI - [The efficacy and prognostic predictors of different treatment courses with pegylated interferon alpha-2a and ribavirin combination in recurrent chronic hepatitis C patients]. AB - OBJECTIVE: To study the efficacy and outcome predictors of combined re-treatment with pegylated interferon (Peg-IFN) alpha-2a and ribavirin in recurrent chronic hepatitis C (CHC) patients. METHODS: A multicenter, prospective, randomized trial was designed. A total of 125 recurrent CHC patients were recruited in 16 clinical centers and randomly assigned into two groups: one was Peg-IFNalpha-2a combined with ribavirin for 48 weeks (group A) and the other the same combination for 72 weeks (group B). HCV RNA levels in patients' serum were detected at baseline, week 4, 12, 24, 48, 72 (group B) after treatment initiation, and 24 weeks after treatment. RESULTS: Of all the 90 patients who completed treatment and 24 weeks follow-up, 80.0% achieved sustained virological response (SVR) yet 12.2% relapsed. There was no significant difference between two groups. The SVR rate in patients previously treated with interferon alone was higher than that in patients with interferon plus ribavirin (92.6% vs 74.6%), but the difference was of no statistical significance (P = 0.05). Moreover, patients previously treated with common interferon (c-IFN) showed a higher SVR rate than patients with Peg IFN (84.7% vs 71.0%, P > 0.05). The positive predictive value (PV) of rapid virological response (RVR) and complete early virological response for SVR was 92.3% and 86.4% respectively, and the negative PV of RVR, early virological response and delayed virological response for SVR was 36.8%, 66.7% and 100.0% respectively. Overall, 62.1% patients reported adverse events (AEs) and 1.6% patients were severe AEs. CONCLUSIONS: A high SVR rate has been achieved in recurrent CHC patients who were retreated with Peg-IFNalpha-2a and ribavirin for 48 weeks. Better SVR cannot be achieved in spite of a prolonged course of 72 weeks. Early virological response at week 12 was the most important predictor for SVR. PMID- 26674627 TI - [The predictive factors of good glycaemic control in Chinese patients receiving biphasic insulin as part 30: a subgroup analyses from the A1 chieve study]. AB - OBJECTIVE: To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c (HbA1c) < 7.0% in Chinese patients receiving biphasic insulin as part 30 (BIAsp 30), who were previously inadequately controlled with oral anti-diabetic drugs (OADs). METHODS: A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician's clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions (SADRs) including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose (FPG), 2h post-prandial plasma glucose (2 hPG) from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c < 7.0% after treatment were examined using multivariate analysis. RESULTS: In China, 4 100 patients initiated BIAsp 30 [54.2% males, age (56.2 +/- 13.6) years]. No SADRs were reported. Mean HbA1c was reduced from (9.3 +/- 2.1)% to (7.0 +/- 1.0)%; FPG was reduced from (10.2 +/- 3.3) mmol/L to (6.8 +/- 1.3) mmol/L. Changes in 2 hPG after breakfast, lunch and dinner were (-5.6 +/ 4.7), (-4.9 +/- 4.3) and (-4.2 +/- 4.1) mmol/L, respectively (all P < 0.001). The proportion of patients achieving HbA1c < 7.0% increased from 9.7% at baseline to 54.2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbA1c, FPG, 2 hPG and HbA1c < 7.0% after treatment. CONCLUSIONS: In the Chinese subgroup of the A1 chieve study, lower baseline HbA1c, FPG, 2 hPG were predictive factors for achieving HbA1c < 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target. PMID- 26674628 TI - [The value of chest computerized tomography in evaluation of bone disease and clinical prognosis of multiple myeloma]. AB - OBJECTIVE: To assess the status and severity of bone disease in patients with multiple myeloma (MM) by using chest computerized tomography (CT) and the relationship between clinical prognostic parameters and bone disease. METHODS: All 46 newly diagnosed MM in-patients received both imaging tests of chest CT and plain X ray. An experienced radiologist reviewed all the imaging data. Clinical laboratory parameters, stages of Durie-Salmon (DS) and International Staging System (ISS) were evaluated. Five cytogenetic abnormalities of bone marrow myeloma cells were tested by fluorescence in situ hybridization (FISH). RESULTS: The sensitivity of CT and X ray to determine pathological fractures was comparable, the positive rates of which were 41.3% (19/46) and 30.4% (14/46) respectively (P = 0.29). Nevertheless, the positive rate of osteolytic lesions ascertained by CT was significantly higher than that by X ray (P < 0.001), 60.9% (28/46) vs 13.0% (6/46) with diameter 5-10 mm and 50.0% (23/46) vs 10.9% (5/46) with diameter more than 10 mm. Osteolytic lesion numbers found by CT were more than those by X ray [5(0-21) vs 0(0-4) lesions with diameter 5-10 mm (P < 0.001), 2(0-14) vs 0(0-2) lesions with diameter more than 10 mm (P < 0.001), respectively]. Patients with positive osteolytic lesions had higher percentage of RB1 gene deletion [46.7% (14/30) vs 18.8% (3/16), P < 0.001], D13s319 deletion [43.3% (13/30) vs 18.8% (3/16), P < 0.001] and high risk cytogenetic abnormalities [50.0% (15/30) vs 25.0% (4/16), P < 0.001]. CONCLUSIONS: Chest CT is more sensitive than plain X ray in detecting osteolytic myeloma bone disease. Osteolysis determined by CT is relevant to clinical DS stages and risk stratification of cytogenetic abnormalities. PMID- 26674629 TI - [The clinical and muscular pathological features of statin-induced myopathy]. AB - OBJECTIVE: To explore clinical and muscular pathological features of statin induced myopathy. METHODS: Nine patients were enrolled in this study, who were diagnosed as statin-induced myopathy by muscle biopsy in Peking University First Hospital from April, 2012 to October, 2014. The clinical data and pathological findings were analyzed. RESULTS: The exposure time to statins varied from 4 days to 4 years in the total of 9 patients, 6 males and 3 females, with the average age of 63 +/- 6 (55 to 74) years old. Three patients suffered from myalgia and 6 patients complained of weakness mainly at the proximal limbs, while no symptoms occured in 3 patients. Serum creatine kinase (CK) increased in all patients with the maximum value varied from 468 to 8 000 U/L. Serum myositis antibodies were tested in 7 patients and all were negative. Electromyogram was performed in six patients with myogenic damage found in 2 patients. MRI of bilateral thigh muscle was carried out in six patients with muscle edema and mild fatty infiltration found in 2 patients. All patients underwent skeletal muscle biopsy with histochemical and immunohistochemical staining. The main muscular pathological features were muscle fiber atrophy, necrosis, regeneration and increased lipid droplets. Ragged blue fiber, cytochrome C oxidase-negative muscle fibers and decreased NADH activity were observed in some patients. MHC-I expressed in the sarcolemma of muscle fibers at various levels. Mild C5b-9 staining was found in the endomysium, capillary and cytoplasm. Symptoms and the level of CK were improved in 7 patients after discontinuing statins or changing to another statin, while the immunosuppressive therapy were used in 2 patients and shown to be effective. CONCLUSIONS: Statin induced myopathy is self-limiting in most patients, with improvement after discontinuation of statins. Few patients with autoimmune necrotic myopathy need immunosuppressive therapy. PMID- 26674630 TI - [To evaluate the cervical spine curvature and growth rate for studying the pathogenesis of Hirayama disease in adolescents]. AB - OBJECTIVE: To explore the pathogenesis of Hirayama disease from juvenile cervical curvature and growth rate. METHODS: Totally 60 patients diagnosed with Hirayama disease (HD) from 2009 to 2011 in our hospital were included in the present study. Patient's height and growth rate 1-2 years prior to the onset of disease were recalled by patients and family members. Lateral cervical X-ray was examined, and cervical curvature was measured by Borden's method. RESULTS: All the patients were adolescents with onset age at 12-25 (17.0 +/- 2.4) years old and peak age of onset at 15-18 [45 cases (75.0%)]. Fifty-seven cases were male and 3 cases were female. Cervical MRI examination of the 60 cases showed that the spinal cord atrophy involving C4-C8 vertebral level. The C line values for cervical curvature by Borden's method of the patients was 2.6 (1.2, 4.2) mm. Among 60 patients, 57 of them were with abnormal cervical curvature. The average height growth rate 1 year prior to the onset was (7.1 +/- 1.8) cm. CONCLUSIONS: The clinical manifestations that featured in overgrowth in the first two years and abnormal cervical vertebra curvature are possible related with pathogenesis of HD. HD is possibly a cervical spinal cord compression disease, which is associated with cervical spinal dysplasia during juvenile growth. PMID- 26674632 TI - Cognitive-behavioural therapy for insomnia: effective, long-lasting and safe. PMID- 26674631 TI - Neighborhood Social Predictors of Weight-related Measures in Underserved African Americans in the PATH Trial. AB - African Americans have the highest rate of obesity in the United States relative to other ethnic minority groups. Bioecological factors including neighborhood social and physical environmental variables may be important predictors of weight related measures specifically body mass index (BMI) in African American adults. Baseline data from the Positive Action for Today's Health (PATH) trial were collected from 417 African American adults. Overall a multiple regression model for BMI was significant, showing positive associations with average daily moderate-to-vigorous physical activity (MVPA) (B =-.21, P<.01) and neighborhood social interaction (B =-.13, P<.01). Consistent with previous literature, results show that neighborhood social interaction was associated with healthier BMI, highlighting it as a potential critical factor for future interventions in underserved, African American communities. PMID- 26674633 TI - Preschool hyperactivity increases costs into early adulthood. PMID- 26674635 TI - Corrigendum: Phytogenic Feed Additives as an Alternative to Antibiotic Growth Promoters in Broiler Chickens. AB - [This corrects the article on p. 21 in vol. 2, PMID: 26664950.]. PMID- 26674634 TI - Cortical Responsiveness to Nociceptive Stimuli in Patients with Chronic Disorders of Consciousness: Do C-Fiber Laser Evoked Potentials Have a Role? AB - It has been shown that the presence of Adelta-fiber laser evoked potentials (Adelta-LEP) in patients suffering from chronic disorders of consciousness (DOC), such as vegetative state (VS) and minimally conscious state (MCS), may be the expression of a residual cortical pain arousal. Interestingly, the study of C fiber LEP (C-LEP) could be useful in the assessment of cortical pain arousal in the DOC individuals who lack of Adelta-LEP. To this end, we enrolled 38 DOC patients following post-anoxic or post-traumatic brain injury, who met the international criteria for VS and MCS diagnosis. Each subject was clinically evaluated, through the coma recovery scale-revised (CRS-R) and the nociceptive coma scale-revised (NCS-R), and electrophysiologically tested by means of a solid state laser for Adelta-LEP and C-LEP. VS individuals showed increased latencies and reduced amplitudes of both the Adelta-LEP and C-LEP components in comparison to MCS patients. Although nearly all of the patients had both the LEP components, some VS individuals showed only the C-LEP ones. Notably, such patients had a similar NCS-R score to those having both the LEP components. Hence, we could hypothesize that C-LEP generators may be rearranged or partially spared in order to still guarantee cortical pain arousal when Adelta-LEP generators are damaged. Therefore, the residual presence of C-LEP should be assessed when Adelta-LEP are missing, since a potential pain experience should be still present in some patients, so to properly initiate, or adapt, the most appropriate pain treatment. PMID- 26674636 TI - Mutual regulation causes co-entrainment between a synthetic oscillator and the bacterial cell cycle. AB - The correct functioning of cells requires the orchestration of multiple cellular processes, many of which are inherently dynamical. The conditions under which these dynamical processes entrain each other remain unclear. Here we use synthetic biology to address this question in the case of concurrent cellular oscillations. Specifically, we study at the single-cell level the interaction between the cell division cycle and a robust synthetic gene oscillator in Escherichia coli. Our results suggest that cell division is able to partially entrain the synthetic oscillations under normal growth conditions, by driving the periodic replication of the genes involved in the oscillator. Coupling the synthetic oscillations back into the cell cycle via the expression of a key regulator of chromosome replication increases the synchronization between the two periodic processes. A simple computational model allows us to confirm this effect. PMID- 26674637 TI - A Fish Assemblage from the Middle Eocene from Libya (Dur At-Talah) and the Earliest Record of Modern African Fish Genera. AB - In the early nineteen sixties, Arambourg and Magnier found some freshwater fish (i.e., Polypterus sp., Siluriformes indet. and Lates sp.) mixed with marine members in an Eocene vertebrate assemblage at Gebel Coquin, in the southern Libyan Desert. This locality, aged ca 37-39Ma and now known under the name of Dur At-Talah, has been recently excavated. A new fish assemblage, mostly composed of teeth, was collected by the Mission Paleontologique Franco-Libyenne. In this paper, we describe freshwater fish members including a dipnoan (Protopterus sp.), and several actinopterygians: bichir (Polypterus sp.), aba fish (Gymnarchus sp.), several catfishes (Chrysichthys sp. and a mochokid indet.), several characiforms (including the tiger fish Hydrocynus sp., and one or two alestin-like fish), and perciforms (including the snake-head fish Parachanna sp. and at least one cichlid). Together with the fossiliferous outcrops at Birket Qarun in Egypt, the Libyan site at Dur At-Talah reduces a 10-Ma chronological gap in the fossil record of African freshwater fish. Their fish assemblages overlap in their composition and thus constitute a rather homogenous, original and significant amount of new elements regarding the Paleogene African ichthyofauna. This supports the establishment of the modern African freshwater fish fauna during this time period because these sites mostly contain the earliest members known in modern genera. PMID- 26674638 TI - Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies. AB - OBJECTIVE: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. METHODS: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. RESULTS: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 +/- 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual perceptual domain were present in both MCI-DLB and AD. CONCLUSIONS: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB. PMID- 26674639 TI - Discovering Molecules That Regulate Efferocytosis Using Primary Human Macrophages and High Content Imaging. AB - Defective clearance of apoptotic cells can result in sustained inflammation and subsequent autoimmunity. Macrophages, the "professional phagocyte" of the body, are responsible for efficient, non-phlogistic, apoptotic cell clearance. Controlling phagocytosis of apoptotic cells by macrophages is an attractive therapeutic opportunity to ameliorate inflammation. Using high content imaging, we have developed a system for evaluating the effects of antibody treatment on apoptotic cell uptake in primary human macrophages by comparing the Phagocytic Index (PI) for each antibody. Herein we demonstrate the feasibility of evaluating a panel of antibodies of unknown specificities obtained by immunization of mice with primary human macrophages and show that they can be distinguished based on individual PI measurements. In this study ~50% of antibodies obtained enhance phagocytosis of apoptotic cells while approximately 5% of the antibodies in the panel exhibit some inhibition. Though the specificities of the majority of antibodies are unknown, two of the antibodies that improved apoptotic cell uptake recognize recombinant MerTK; a receptor known to function in this capacity in vivo. The agonistic impact of these antibodies on efferocytosis could be demonstrated without addition of either of the MerTK ligands, Gas6 or ProS. These results validate applying the mechanism of this fundamental biological process as a means for identification of modulators that could potentially serve as therapeutics. This strategy for interrogating macrophages to discover molecules regulating apoptotic cell uptake is not limited by access to purified protein thereby increasing the possibility of finding novel apoptotic cell uptake pathways. PMID- 26674640 TI - Puncture Reduction in Percutaneous Transforaminal Endoscopic Discectomy with HE's Lumbar LOcation (HELLO) System: A Cadaver Study. AB - BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) usually requires numerous punctures under X-ray fluoroscopy. Repeated puncture will lead to more radiation exposure and reduce the beginners' confidence. OBJECTIVE: This cadaver study aimed to investigate the efficacy of HE's Lumbar Location (HELLO) system in puncture reduction of PTED. STUDY DESIGN: Cadaver study. SETTING: Comparative groups. METHODS: HELLO system consists of self-made surface locator and puncture locator. One senior surgeon conducted the puncture procedure of PTED on the left side of 20 cadavers at L4/L5 and L5/S1 level with the assistance of HELLO system (Group A). Additionally, the senior surgeon conducted the puncture procedure of PTED on the right side of the cadavers at L4/L5 and L5/S1 level with traditional methods (Group B). On the other hand, an inexperienced surgeon conducted the puncture procedure of PTED on the left side of the cadavers at L4/L5 and L5/S1 level with the assistance of our HELLO system (Group C). RESULTS: At L4/L5 level, there was significant difference in puncture times between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.811). Similarly at L5/S1 level, there was significant difference in puncture times between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.981). At L4/L5 level, there was significant difference in fluoroscopy time between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.290). Similarly at L5/S1 level, there was significant difference in fluoroscopy time between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.523). As for radiation exposure, HELLO system reduced 39%-45% radiation dosage when comparing Group A and Group B, but there was no significant difference in radiation exposure between Group A and Group C whatever at L4/L5 level or L5/S1 level (P>0.05). There was no difference in location time between Group A and Group B or Group A and Group C either at L4/L5 level or L5/S1 level (P>0.05). LIMITATIONS: Small-sample preclinical study. CONCLUSION: HELLO system was effective in reducing puncture times, fluoroscopy time and radiation exposure, as well as the difficulty of learning PTED. (2015-RES-127). PMID- 26674641 TI - Synergism of MSC-secreted HGF and VEGF in stabilising endothelial barrier function upon lipopolysaccharide stimulation via the Rac1 pathway. AB - BACKGROUND: Mesenchymal stem cells (MSCs) stabilise endothelial barrier function in acute lung injury via paracrine hepatocyte growth factor (HGF). Vascular endothelial growth factor (VEGF), which is secreted by MSCs, is another key regulator of endothelial permeability; however, its role in adjusting permeability remains controversial. In addition, whether an interaction occurs between HGF and VEGF, which are secreted by MSCs, is not completely understood. METHODS: We introduced a co-cultured model of human pulmonary microvascular endothelial cells (HPMECs) and MSC conditioned medium (CM) collected from MSCs after 24 h of hypoxic culture. The presence of VEGF and HGF in the MSC-CM was neutralised by anti-VEGF and anti-HGF antibodies, respectively. To determine the roles and mechanisms of MSC-secreted HGF and VEGF, we employed recombinant humanised HGF and recombinant humanised VEGF to co-culture with HPMECs. Additionally, we employed the RhoA inhibitor C3 transferase and the Rac1 inhibitor NSC23766 to inhibit the activities of RhoA and Rac1 in HPMECs treated with MSC-CM or VEGF/HGF with the same dosage as in the MSC-CM. Then, endothelial paracellular and transcellular permeability was detected. VE-cadherin, occludin and caveolin-1 protein expression in HPMECs was measured by western blot. Adherens junction proteins, including F-actin and VE-cadherin, were detected by immunofluorescence. RESULTS: MSC-CM treatment significantly decreased lipopolysaccharide-induced endothelial paracellular and transcellular permeability, which was significantly inhibited by pretreatment with HGF antibody or with both VEGF and HGF antibodies. Furthermore, MSC-CM treatment increased the expression of the endothelial intercellular adherence junction proteins VE cadherin and occludin and decreased the expression of caveolin-1 protein. MSC-CM treatment also decreased endothelial apoptosis and induced endothelial cell proliferation; however, the effects of MSC-CM treatment were inhibited by pretreatment with HGF antibody or with both HGF and VEGF antibodies. Additionally, the effects of MSC-CM and VEGF/HGF on reducing endothelial paracellular and transcellular permeability were weakened when HPMECs were pretreated with the Rac1 inhibitor NSC23766. CONCLUSION: HGF secreted by MSCs protects the endothelial barrier function; however, VEGF secreted by MSCs may synergize with HGF to stabilise endothelial cell barrier function. Rac1 is the pathway by which MSC-secreted VEGF and HGF regulate endothelial permeability. PMID- 26674642 TI - Trichosporon heliocopridis sp. nov., a urease-negative basidiomycetous yeast associated with dung beetles (Heliocopris bucephalus Fabricius). AB - Ninety-six yeast isolates associated with dung beetles (Heliocopris bucephalus Fabricius) were examined based on a culture-dependent method. A comparison of the colony morphology and PCR-fingerprints obtained by (GTG)5 microsatellite-primed PCR indicated that 84 of these isolates belonged to one group. Five strains (DD1 1T, DD2-33, DD4-11, DD5-15 and DD6-1) were selected as the representatives of this main group, where each of the five selected strains had been derived from a different dung beetle collected in northern Thailand. A comparison of the D1/D2 domain sequence of the large subunit rRNA gene (LSU D1/D2) and the internal transcribed spacer (ITS) sequences revealed that these five strains were the same and were related to the genus Trichosporon. Phylogenetic analysis based on the LSU D1/D2 plus ITS sequences placed this group within the Trichosporon brassicae clade, but it was clearly separated from any known species. In addition, physiological tests showed that this group had the unusual property of the inability to hydrolyse urea, which was distinctly different from the related taxon. Therefore a novel yeast species named Trichosporon heliocopridis sp. nov. (ex-type strain DD1-1T = TISTR 5946T = JCM 30786T = CBS 14168T) is proposed. The MycoBank number is MB812098. PMID- 26674643 TI - Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect. AB - Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS) in semi-field conditions and long lasting insecticidal nets (LLINs) in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46%) but high for other predominant species such as Mansonia africana (93% to 97%). There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001). Furthermore, mortality was 23.71% for OlyseNet(r) and 39.06% for PermaNet(r). However, with laboratory susceptible "Kisumu", mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted. PMID- 26674645 TI - Stair Climbing Test Streamlines the Evaluation of Nonmalignant Lung Resection Candidates. PMID- 26674644 TI - RUNX1-Evi-1 fusion gene inhibited differentiation and apoptosis in myelopoiesis: an in vivo study. AB - BACKGROUND: Acute myeloid leukemia (AML) 1-Evi-1 is a chimeric gene generated by the t (3; 21) (q26; q22) translocation, which leads into malignant transformation of hematopoietic stem cells by unclear mechanisms. This in vivo study aimed to establish a stable line of zebrafish expressing the human RUNX1-Evi-1 fusion gene under the control of a heat stress-inducible bidirectional promoter, and investigate its roles in hematopoiesis and hematologic malignancies. METHODS: We introduced human RUNX1-Evi-1 fusion gene into embryonic zebrafish through a heat shock promoter to establish Tg(RE:HSE:EGFP) zebrafish. Two males and one female mosaic F0 zebrafish embryos (2.1%) were identified as stable positive germline transgenic zebrafish. RESULTS: The population of immature myeloid cells and hematopoietic blast cells were accumulated in peripheral blood and single cell suspension from kidney of adult Tg(RE:HSE:EGFP) zebrafish. RUNX1-Evi-1 presented an intensive influence on hematopoietic regulatory factors. Consequently, primitive hematopoiesis was enhanced by upregulation of gata2 and scl, while erythropoiesis was downregulated due to the suppression of gata1. Early stage of myelopoiesis was flourishing with the high expression of pu.1, but it was inhibited along with the low expression of mpo. Microarray analysis demonstrated that RUNX1-Evi-1 not only upregulated proteasome, cell cycle, glycolysis/gluconeogenesis, tyrosine metabolism, drug metabolism, and PPAR pathway, but also suppressed transforming growth factor beta, Jak-STAT, DNA replication, mismatch repair, p53 pathway, JNK signaling pathway, and nucleotide excision repair. Interestingly, histone deacetylase 4 was significantly up regulated. Factors in cell proliferation were obviously suppressed after 3-day treatment with histone deacetylase inhibitor, valproic acid. Accordingly, higher proportion of G1 arrest and apoptosis were manifested by the propidium iodide staining. CONCLUSION: RUNX1-Evi-1 may promote proliferation and apoptosis resistance of primitive hematopoietic cell, and inhibit the differentiation of myeloid cells with the synergy of different pathways and factors. VPA may be a promising choice in the molecular targeting therapy of RUNX1-Evi-1-related leukemia. PMID- 26674646 TI - Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers. AB - COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID- 26674648 TI - An Unrecorded Pre-Pre-Analytical Error in Serum Iron Analysis. PMID- 26674647 TI - Health promotion programme design and efficacy in relation to ageing persons with culturally and linguistically diverse backgrounds: a systematic literature review and meta-analysis. AB - BACKGROUND: Health promotion has the potential to empower people to develop or maintain healthy lifestyles. However, previous research has visualised serious health and healthcare inequities associated with ageing, cultural affiliations and linguistic preferences. Therefore, this study was part of a larger health promotion project, set out to bridge barriers to health for ageing persons who have migrated to Sweden. More specifically, the present study aimed to elucidate the content and effects of multidimensional health promotion programmes in the context of ageing persons with culturally and linguistically diverse backgrounds. METHODS: Databases were systematically searched to identify relevant randomised controlled trial publications. All potentially relevant publications were assessed for relevance and design and after this screening, a final sample of eight publications could be included in the review. Those publications evaluated six different programmes and a mixed-methods approach to data analysis was applied, using a combination of narrative synthesis, meta-analyses and evidence grading. RESULTS: The findings suggest a multidimensional health promotion programme design for ageing persons with culturally and linguistically diverse backgrounds, involving culturally and linguistically modified activities and health information that should be provided by professionals with a person-centred approach. In addition, the meta-analyses revealed statistically significant effects in favour of health promotion on: general health, depression, mental health, physical health, and vitality. However, the evidence for the identified effects is low, and further research findings are likely to change the estimations. CONCLUSIONS: The present study provides an aggregation of health promotion intervention research with older persons with culturally and linguistically diverse backgrounds; a group of people who are commonly excluded from research, and marginalised when it comes to health and healthcare. By visualising the core components of health promotion programmes with proven efficacy, the findings provide guidance for further explorations of how health promotion should be designed to minimise inequities in health. PMID- 26674649 TI - Effective universal health coverage and improved 1-year survival after acute myocardial infarction: the Chilean experience. AB - In 2005, Chile implemented a universal system of health guarantees (AUGE) aimed at improving equitable access to quality medical care for priority health conditions, including acute myocardial infarction (MI). OBJECTIVE: To evaluate 1 year survival in MI patients before and after AUGE. METHODS: Retrospective cohorts of patients with MI (with and without ST segment elevation) discharged alive from six public hospitals between January 2001-June 2005 (pre-AUGE) and July 2008-March 2009 (post-AUGE). Chilean national mortality and MI Registry (hospital-based) databases were linked using a unique identification number (ICD 10 codes I00-I99 were used to identify cardiovascular deaths). One-year survival was assessed using Weibull multivariate regression. RESULTS: About 1867 patients were discharged alive pre-AUGE and 534 post-AUGE; 25% were women in both periods. When comparing pre-AUGE and post-AUGE, there was an increase in the use of primary and elective angioplasty (1.7 vs 23.6% and 7.3 vs 20.0%), beta-blockers (62 vs 71%) and statins (40 vs 90%); P < 0.001 all. One-year survival was 92% pre-AUGE (95% CI: 91-93%) and 96% post-AUGE (95% CI: 94-97%) (HR = 0.50, 95% CI: 0.31-0.82; P = 0.003). The post-AUGE improvement persisted after adjusting for variables associated with long-term case-fatality (HR = 0.44, 95% CI: 0.26 0.75). Percutaneous coronary intervention (HR = 0.31, 95% CI: 0.09-0.99) and statins use at discharge (HR = 0.45, 95% CI: 0.31-0.66) had the highest effects associated with lower case-fatality and both treatments increased in the post AUGE period. CONCLUSIONS: The implementation of AUGE in Chile appears to have contributed to improved treatment of MI in public hospitals and increased 1-year survival, which is consistent with its aim to improve access to quality medical care and to reduce health inequities. PMID- 26674650 TI - Promising clinical practices of metformin in women with PCOS and early-stage endometrial cancer. AB - Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial cancer (EC). There is an urgent need for non-surgical prevention and treatment strategies for these patients who fail to respond to progesterone treatment and wish to preserve their fertility. Recently, we have reported that the combined treatment with metformin and progesterone-based oral contraceptives has successfully reversed the early-stage EC into normal endometria in addition to improvement of insulin resistance in women with PCOS. More importantly, one of these treated women has successfully delivered a healthy newborn baby. However, before such treatment can be recommended to the clinical practice, the molecular basis of metformin in the endometrium under physiological and pathological conditions must be elucidated. PMID- 26674651 TI - Cellular Antiviral Factors that Target Particle Infectivity of HIV-1. AB - BACKGROUND: In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. CONCLUSION: A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated. PMID- 26674652 TI - The Effect of Intra-articular Corticosteroids on Articular Cartilage: A Systematic Review. AB - BACKGROUND: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. PURPOSE: To review the current literature on the effects of IA corticosteroids on articular cartilage. STUDY DESIGN: Systematic review. METHODS: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. RESULTS: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. CONCLUSION: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID- 26674654 TI - Sir Victor Horsley at the birth of neurosurgery. PMID- 26674653 TI - Migraine induced by hypoxia: an MRI spectroscopy and angiography study. AB - Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P < 0.05). We found no difference in the metabolic or vascular responses to hypoxia between migraine patients and controls. In conclusion, hypoxia induced migraine-like attacks with and without aura and dilated the cranial arteries in patients with migraine with aura. Hypoxia-induced attacks were not associated with altered concentration of glutamate or other metabolites. The present study suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated. PMID- 26674656 TI - Effect of Different Anti-Oxidants on Shear Bond Strength of Composite Resins to Bleached Human Enamel. AB - INTRODUCTION: The bond strength of the composite to the bleached enamel plays a very important role in the success and longevity of an aesthetic restoration. AIM: The aim of this study was to compare and evaluate the effect of Aloe Vera with 10% Sodium Ascorbate on the Shear bond strength of composite resin to bleached human enamel. MATERIALS AND METHODS: Fifty freshly extracted human maxillary central incisors were selected and divided into 5 groups. Group I and V are unbleached and bleached controls groups respectively. Group II, III, IV served as experimental groups. The labial surfaces of groups II, III, IV, V were treated with 35% Carbamide Peroxide for 30mins. Group II specimens were subjected to delayed composite bonding. Group III and IV specimens were subjected to application of 10% Sodium Ascorbate and leaf extract of Aloe Vera following the Carbamide Peroxide bleaching respectively. Specimens were subjected to shear bond strength using universal testing machine and the results were statistically analysed using ANOVA test. Tukey (HSD) Honest Significant Difference test was used to comparatively analyse statistical differences between the groups. A p value <0.05 is taken as statistically significant. RESULTS: The mean shear bond strength values of Group V showed significantly lower bond strengths than Groups I, II, III, IV (p-value <0.05). There was no statistically significant difference between the shear bond strength values of groups I, II, III, IV. CONCLUSION: Treatment of the bleached enamel surface with Aloe Vera and 10% Sodium Ascorbate provided consistently better bond strength. Aloe Vera may be used as an alternative to 10% Sodium Ascorbate. PMID- 26674658 TI - Ultrafine-Particle Emission Factors as a Function of Vehicle Mode of Operation for LDVs Based on Near-Roadway Monitoring. AB - This paper presents ultrafine-particle (UFP) emission factors (EFs) as a function of vehicle mode of operation (free flow and congestion) using (1) concurrent 5 min measurements of UFPs and carbon monoxide (CO) concentration, wind speed and direction, traffic volume and speed near a roadway that is restricted to light duty vehicles (LDVs) and (2) inverse dispersion model calculations. Short-term measurements are required to characterize the highly variable and rapidly changing UFP concentration generated by vehicles. Under congestion conditions, the UFP vehicle EFs increased from 0.5 * 10(13) to 2 * 10(13) (particles km(-1) vehicle(-1)) when vehicle flow increased from 5500 to 7500 vehicles/h. For free flow conditions, the EF is constant at 1.5 * 10(13) (particles km(-1) vehicle( 1)). The analysis is based on the assumption that air-quality models adequately describe the dilution process due to both traffic and atmospheric turbulence. The approach used to verify this assumption was to use an emission factor model to determine EFs for CO and then estimate dilution factors using measured CO concentrations. This procedure eliminates the need to rely only on air quality models to generate dilution factors. The EFs are suitable for fleet emissions under real-world traffic conditions. PMID- 26674657 TI - Evaluation of Respiratory Muscle Strength and Pulmonary Function in Patients with Charcot-Marie-Tooth Disease Type 2. AB - The aim of this study was to evaluate the pulmonary condition in a large family with Charcot-Marie-Tooth disease type 2 (CMT2). Eighteen participants diagnosed with CMT2 and 20 healthy individuals were evaluated by spirometry and maximal expiratory and maximal inspiratory pressures (MEP and MIP, respectively). Clinical disability was measured with CMT neuropathy score (CMTNS; range 0-36). One control group (CG) comprising 20 individuals, matched for age, sex and body mass index, were used for comparison. Eight patients were female (44.5%) and 10 patients were male (55.5%); mean age was 31.8 years (range 11-79) and CMTNS range was 6-26. Differences between CMT2 and CG in the spirometry and respiratory muscle strength were statistically significant for all dimensions. There were significant correlations between CMTNS and MIP (Pearson = -0.581) and MEP (Pearson = -0.5090). The results of this study show that patients with CMT, in spite of not showing clinical signs of advanced respiratory impairment, may present subclinical respiratory changes. The respiratory comprise in the CMT disease can be silent and insidious without presenting characteristic clinical signals. PMID- 26674655 TI - Clinical features of TBK1 carriers compared with C9orf72, GRN and non-mutation carriers in a Belgian cohort. AB - We identified in a cohort of patients with frontotemporal dementia (n = 481) or amyotrophic lateral sclerosis (n = 147), 10 index patients carrying a TBK1 loss of function mutation reducing TBK1 expression by 50%. Here, we describe the clinical and pathological characteristics of the 10 index patients and six of their affected relatives carrying a TBK1 mutation. Six TBK1 carriers were diagnosed with frontotemporal dementia, seven with amyotrophic lateral sclerosis, one with both clinical phenotypes and two with dementia unspecified. The mean age at onset of all 16 TBK1 carriers was 62.1 +/- 8.9 years (range 41-73) with a mean disease duration of 4.7 +/- 4.5 years (range 1-13). TBK1 carriers with amyotrophic lateral sclerosis had shorter disease duration than carriers with frontotemporal dementia. Six of seven TBK1 carriers were diagnosed with the behavioural variant of frontotemporal dementia, presenting predominantly as disinhibition. Memory loss was an important associated symptom in the initial phase of the disease in all but one of the carriers with frontotemporal dementia. Three of the patients with amyotrophic lateral sclerosis exhibited pronounced upper motor neuron symptoms. Overall, neuroimaging displayed widespread atrophy, both symmetric and asymmetric. Brain perfusion single-photon emission computed tomography or fluorodeoxyglucose-positron emission tomography showed asymmetric and predominantly frontotemporal involvement. Neuropathology in two patients demonstrated TDP-43 type B pathology. Further, we compared genotype-phenotype data of TBK1 carriers with frontotemporal dementia (n = 7), with those of frontotemporal dementia patients with a C9orf72 repeat expansion (n = 65) or a GRN mutation (n = 52) and with frontotemporal dementia patients (n = 259) negative for mutations in currently known causal genes. TBK1 carriers with frontotemporal dementia had a later age at onset (63.3 years) than C9orf72 carriers (54.3 years) (P = 0.019). In clear contrast with TBK1 carriers, GRN carriers were more often diagnosed with the language variant than the behavioural variant, and presented in case of the diagnosis of behavioural variant, more often than TBK1 carriers with apathy as the predominant characteristic (P = 0.004). Also, TBK1 carriers exhibited more often extrapyramidal symptoms than C9orf72 carriers (P = 0.038). In conclusion, our study identified clinical differences between the TBK1, C9orf72 and GRN carriers, which allows us to formulate guidelines for genetic diagnosis. After a negative result for C9orf72, patients with both frontotemporal dementia and amyotrophic lateral sclerosis should be tested first for mutations in TBK1. Specifically in frontotemporal dementia patients with early memory difficulties, a relatively late age at onset or extrapyramidal symptoms, screening for TBK1 mutations should be considered. PMID- 26674659 TI - Rare Neoplasia of the Stomach. AB - BACKGROUND: Gastric adenocarcinoma accounts for more than 90% of malignant lesions of the stomach. Besides this entity, numerous neoplastic lesions with malignant or benign characteristics as well as lesions with uncertain malignant potential occur. This review gives an overview on rare neoplasia of the stomach, focusing on gastric polyps, gastrointestinal stromal tumors, gastric lymphoma and neuroendocrine neoplasia. SUMMARY: A broad spectrum of rare neoplastic lesions of the stomach with significant differences in malignant potential and with specific demands of interventional therapy is known. In addition to the use of high definition endoscopy techniques, the histopathological assessment of lesions and of the surrounding mucosa is mandatory to characterize and differentiate malignant and benign tumors. KEY MESSAGE: Rare neoplasia of the stomach is detected in approximately 6% of patients undergoing esophagogastroduodenoscopy. Diligent examination of the gastric mucosa remains essential to detect mucosal and submucosal lesions. PRACTICAL IMPLICATIONS: Presenting with a broad spectrum of symptoms, ranging from unspecific abdominal discomfort to gastrointestinal bleeding or symptoms of gastric outlet obstruction, different rare neoplastic lesions of the stomach with demand of specific diagnostic and therapeutic work-up occur. Diligent endoscopic evaluation of the entire gastric mucosa, preferably by high-definition endoscopy techniques, is essential in addition to histopathological examination of lesional and surrounding tissue. PMID- 26674660 TI - Primary Squamous Cell Carcinoma of Urinary Bladder - A Rare Histological Variant. AB - Primary squamous cell carcinoma of urinary bladder is a rare histological variant of epithelial bladder tumours. Histopathological types are associated with significant disease outcome, so it is essential to find, on microscopy the exact type of urothelial carcinoma. Herewith, we present a 70-year-old male having 3 months history of difficulty in micturition, reduced frequency of urine and associated pain. On Contrast Enhanced CT scan abdomen pelvis, showed irregular large urinary bladder mass with hydroureter and hydronephrosis. Internal iliac group of lymphnodes was enlarged. On histopathology diagnosed as pure squamous cell carcinoma of urinary bladder grade II with muscle invasion. We are presenting this case for its clinical, radiological and histopathological findings. PMID- 26674661 TI - IMMEDIATE EFFECTS OF A DYNAMIC ROTATION-SPECIFIC WARM-UP ON X-FACTOR AND X-FACTOR STRETCH IN THE AMATEUR GOLFER. AB - BACKGROUND: Recent evidence suggests performing a warm-up prior to golf can improve performance and reduce injuries. While some characteristics of effective golf warm-ups have been determined, no studies have explored the immediate effects of a rotational-specific warm-up with elements of motor control on the biomechanical aspects of the full X-Factor and X-Factor Stretch during the golf swing. METHODS: Thirty-six amateur golfers (mean +/- SD age: 64 +/- 8 years old; 75% male) were randomized into a Dynamic Rotation-Specific Warm-up group (n=20), or a Sham Warm-up group (n=16). X-Factor and X-Factor Stretch were measured at baseline and immediately following the warm-up. Mixed model ANCOVAs were used to determine if a Group*Time interaction existed for each variable with group as the between-subjects variable and time as the within-subjects variable. RESULTS: The mixed model ANCOVAs did not reveal a statistically significant group*time interaction for X-Factor or X-Factor Stretch. There was not a significant main effect for time for X-Factor but there was for X-Factor Stretch. These results indicate that neither group had a significant effect on improving X-Factor, however performing either warm-up increased X-Factor Stretch without significant difference between the two. CONCLUSIONS: The results of this study suggest that performing the Dynamic Rotation-Specific Warm-up did not increase X-Factor or X Factor Stretch when controlled for age compared to the Sham Warm-up. Further study is needed to determine the long-term effects of the Dynamic Rotation Specific Warm-up on performance factors of the golf swing while examining across all ages. LEVEL OF EVIDENCE: 2b. PMID- 26674662 TI - Pattern of circulating microparticles in chronic heart failure patients with metabolic syndrome: Relevance to neurohumoral and inflammatory activation. PMID- 26674663 TI - Editorial Comment on: A. Smereczynski, T. Szopinski, T. Golabek, O. Ostasz and S. Bojko Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder. PMID- 26674664 TI - Sonic Hedgehog Signalling Pathway and Ameloblastoma - A Review. AB - Ameloblastoma is a benign but aggressive odontogenic neoplasm arising from odontogenic epithelium. Many theories have been proposed to explain the pathogenesis of ameloblatoma. Numerous signalling pathways have been implicated to be associated in the development and progression of this neoplasm. Studies have found association of various signalling molecules of Sonic Hedgehog Pathway, namely SHH, PTCH1, SMO, Gli 1, Gli 2, Gli 3, with ameloblastoma. Knowledge about this pathway will help us to understand the nature and behaviour of this neoplasm. This will open the door towards new treatment modalities. PMID- 26674666 TI - Sphincter lesions observed on ultrasound after transanal endoscopic surgery. AB - AIM: To assess the morphological impact of transanal endoscopic surgery on the sphincter apparatus using the modified Starck classification. METHODS: A prospective, observational study of 118 consecutive patients undergoing Transanal Endoscopic Operation/Transanal Endoscopic Microsurgery (TEO/TEM) from March 2013 to May 2014 was performed. All the patients underwent an endoanal ultrasound prior to surgery and one and four months postoperatively in order to measure sphincter width, identify sphincter defects and to quantify them in terms of the level, depth and size of the affected anal canal. To assess the lesions, we used the "modified" Starck classification, which incorporates the variable "sphincter fragmentation". The results were correlated with the Wexner incontinence questionnaire. RESULTS: Of the 118 patients, twelve (sphincter lesions) were excluded. The results of the 106 patients were as follows after one month: 31 (29.2%) lesions found on ultrasound after one month, median overall Starck score of 4 (range 3-6); 10 (9.4%) defects in the internal anal sphincter (IAS) and 3 (2.8%) in the external anal sphincter (EAS); 17 patients (16%) had fragmentation of the sphincter apparatus with both sphincters affected in one case. At four months: 7 (6.6%) defects, all in the IAS, overall median Starck score of 4 (range 3-6). Mean IAS widths were 3.5 mm (SD 1.14) preoperatively, 4.38 mm (SD 2.1) one month postoperatively and 4.03 mm (SD 1.46) four months postoperatively. The only statistically significant difference in sphincter width in the IAS measurements was between preoperatively and one month postoperatively. No incontinence was reported, even in cases of ultrasound abnormalities. CONCLUSION: TEO/TEM may produce ultrasound abnormalities but this is not accompanied by clinical changes in continence. The modified Starck classification is useful for describing and managing these disorders. PMID- 26674667 TI - Humanitarian Medical Response to the Syrian Arab Republic (April 7, 2013 to April 23, 2013). AB - The Syrian Arab Republic is entrenched in a deadly civil war, plunging the country into a state of chaos. With 3.2 million refugees abroad, 7.6 million internally displaced persons, and more than 200,000 killed, humanitarian assistance and international intervention are in dire need. This report outlines the response to the Syrian humanitarian crisis by a South African-based nongovernmental organization (NGO). It describes the experiences of a health care worker, the patient profiles, and the lessons learned in a war zone. Responding to a nation in need is of paramount importance. In order to maximize the benefit conferred, the team should always attempt to implement measures that leave a lasting legacy. PMID- 26674665 TI - Significance of ultrasonography in selecting methods for the treatment of acute cholecystitis. AB - Surgical removal of the gallbladder is indicated in nearly all cases of complicated acute cholecystitis. In the 1990s, laparoscopic cholecystectomy became the method of choice in the treatment of cholecystolithiasis. Due to a large inflammatory reaction in the course of acute inflammation, a laparoscopic procedure is conducted in technically difficult conditions and entails the risk of complications. THE AIM OF THIS PAPER: The aim of this paper was: 1) to analyze ultrasound images in acute cholecystitis; 2) to specify the most common causes of conversion from the laparoscopic method to open laparotomy; 3) to determine the degree to which the necessity for such a conversion may be predicted with the help of ultrasound examinations. MATERIAL AND METHODS: In 1993-2011, in the Second Department and Clinic of General, Gastroenterological and Oncological Surgery of the Medical University in Lublin, 5,596 cholecystectomies were performed including 4,105 laparoscopic procedures that constituted 73.4% of all cholecystectomies. Five hundred and forty-two patients (13.2%) were qualified for laparoscopic procedure despite manifesting typical symptoms of acute cholecystitis in ultrasound examination, which comprise: thickening of the gallbladder wall of > 3 mm, inflammatory infiltration in the Calot's triangle region, gallbladder filled with stagnated or purulent contents and mural or intramural effusion. RESULTS: In the group of operated patients, the conversion was necessary in 130 patients, i.e. in 24% of cases in comparison with 3.8% of patients with uncomplicated cholecystolithiasis (without the signs of inflammation). The conversion most frequently occurred when the assessment of the anatomical structures of the Calot's triangle was rendered more difficult due to local inflammatory process, mural effusion and thickening of the gallbladder wall of >5 mm. The remaining changes occurred more rarely. CONCLUSIONS: Based on imaging scans, the most common causes of conversion included inflammatory infiltration in the Calot's triangle region, mural effusion and wall thickening to > 5 mm. The classical cholecystectomy in acute cholecystitis should be performed in patients with three major local complications detected on ultrasound examination and in those, who manifest acute clinical symptoms. PMID- 26674668 TI - Usefulness of protein analysis for detecting pathologies in bone remains. AB - Forensic pathology often uses osteobiography, which involves biological profiles based on a determination of the age, sex, constitution, pathological states and other anomalies (paleopathology) of subjects for identification purposes. In this paper, proteins were analysed in bone remains. A total of 45 long bones from 45 different cadavers (29 males, 16 females) with a mean age of 66.31 years (S.D.=19.48, range 20-97) were used to search for pathological biomarkers which are closely related to several diseases. The bones were removed from the cement niches of a cemetery in Murcia (south-eastern Spain), where they had lain for between 18 and 45 years (mean time 25.84 years, S.D.=8.91). After a specific extraction using Tris-Urea buffer, were measured using HPLC/MS/MS. Our results show that proteins resulting from tumoral diseases and bacterial and viral pathogens can be detected and identified in the skeletal remains, making them useful pathological biomarkers for constructing biological profiles. PMID- 26674669 TI - A generic strategy for CRISPR-Cas9-mediated gene tagging. AB - Genome engineering has been greatly enhanced by the availability of Cas9 endonuclease that can be targeted to almost any genomic locus using so called guide RNAs (gRNAs). However, the introduction of foreign DNA sequences to tag an endogenous gene is still cumbersome as it requires the synthesis or cloning of homology templates. Here we present a strategy that enables the tagging of endogenous loci using one generic donor plasmid. It contains the tag of interest flanked by two gRNA recognition sites that allow excision of the tag from the plasmid. Co-transfection of cells with Cas9, a gRNA specifying the genomic locus of interest, the donor plasmid and a cassette-specific gRNA triggers the insertion of the tag by a homology-independent mechanism. The strategy is efficient and delivers clones that display a predictable integration pattern. As showcases we generated NanoLuc luciferase- and TurboGFP-tagged reporter cell lines. PMID- 26674670 TI - Discrimination Enhancement with Transient Feature Analysis of a Graphene Chemical Sensor. AB - A graphene chemical sensor is subjected to a set of structurally and chemically similar hydrocarbon compounds consisting of toluene, o-xylene, p-xylene, and mesitylene. The fractional change in resistance of the sensor upon exposure to these compounds exhibits a similar response magnitude among compounds, whereas large variation is observed within repetitions for each compound, causing a response overlap. Therefore, traditional features depending on maximum response change will cause confusion during further discrimination and classification analysis. More robust features that are less sensitive to concentration, sampling, and drift variability would provide higher quality information. In this work, we have explored the advantage of using transient-based exponential fitting coefficients to enhance the discrimination of similar compounds. The advantages of such feature analysis to discriminate each compound is evaluated using principle component analysis (PCA). In addition, machine learning-based classification algorithms were used to compare the prediction accuracies when using fitting coefficients as features. The additional features greatly enhanced the discrimination between compounds while performing PCA and also improved the prediction accuracy by 34% when using linear discrimination analysis. PMID- 26674672 TI - Gold Nanoparticle-Decorated Scaffolds Promote Neuronal Differentiation and Maturation. AB - Engineered 3D neuronal networks are considered a promising approach for repairing the damaged spinal cord. However, the lack of a technological platform encouraging axonal elongation over branching may jeopardize the success of such treatment. To address this issue we have decorated gold nanoparticles on the surface of electrospun nanofiber scaffolds, characterized the composite material, and investigated their effect on the differentiation, maturation, and morphogenesis of primary neurons and on an immature neuronal cell line. We have shown that the nanocomposite scaffolds have encouraged a longer outgrowth of the neurites, as judged by the total length of the branching trees and the length and total distance of neurites. Moreover, neurons grown on the nanocomposite scaffolds had less neurites originating out of the soma and lower number of branches. Taken together, these results indicate that neurons cultivated on the gold nanoparticle scaffolds prefer axonal elongation over forming complex branching trees. We envision that such cellular constructs may be useful in the future as implantable cellular devices for repairing damaged neuronal tissues, such as the spinal cord. PMID- 26674673 TI - Prediction of Preeclampsia by First Trimester Combined Test and Simple Complete Blood Count Parameters. AB - INTRODUCTION: Preeclampsia is a serious disease which may result in maternal and neonatal mortality and morbidity. Improving the outcome for preeclampsia necessitates early prediction of the disease to identify women at high risk. Measuring blood cell subtype ratios, such as the neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios, might provide prognostic and diagnostic clues to diseases. AIM: To investigate hematological changes in early pregnancy, using simple complete blood count (CBC) and blood concentrations of beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP A) to determine whether these measures are of any value in the prediction and early diagnosis of preeclampsia. MATERIALS AND METHODS: Six hundred fourteen consecutive pregnant women with preeclampsia (288 with mild disease and 326 with severe disease) and 320 uncomplicated pregnant women were included in the study. Blood samples for routine CBC and first trimester screen, which combines PAPP-A and free beta-hCG blood concentrations, were analyzed. RESULTS: The NLR values were significantly higher in the severe preeclampsia group compared with the control group (p<0.001). We also confirmed that levels of PAPP-A were lower in patients who developed preeclampsia. CONCLUSION: Because measuring CBC parameters, particularly NLR, is fast and easily applicable, they may be used to predict preeclampsia. PMID- 26674674 TI - Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA. AB - High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of "stem like" cells to render them more susceptible to the killing action of cytotoxic anticancer drugs. PMID- 26674675 TI - Effects of Focused Extracorporeal Shock Waves on Bone Marrow Mesenchymal Stem Cells in Patients with Avascular Necrosis of the Femoral Head. AB - To observe the effect of extracorporeal shock waves (ESWs) on bone marrow mesenchymal stem cells (MSCs) in patients with avascular necrosis of the femoral head, we collected bone marrow donated by patients and then cultivated and passaged MSCs in vitro using density gradient centrifugation combined with adherence screening methods. The P3 generation MSCs were divided into the ESW group and the control group. The cell counting kit for MSCs detected some proliferation differences. Cytochemistry, alkaline phosphatase staining and Alizarin red staining were used to determine alkaline phosphatase content. Simultaneously, real-time polymerase factor alpha1, osteocalcin and peroxisome proliferator-activated receptor gamma. Together, the results of our study first indicate that moderate ESW intensity, which is instrumental in enhancing MSC proliferation, inducing conversion of MSCs into osteoblasts, and inhibiting differentiation of MSCs into adipocytes from MSCs, is one of the effective mechanisms for treating avascular necrosis of the femoral head. PMID- 26674676 TI - Fluid Viscosity Affects the Fragmentation and Inertial Cavitation Threshold of Lipid-Encapsulated Microbubbles. AB - Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (~4 cP). In this study, ultrahigh-speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25-2 MPa). The propensity for individual microbubble (n = 220) fragmentation was found to significantly decrease in 4-cP fluid compared with 1-cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4-cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g., ultraharmonic) with increasing pressure, compared with those in 1-cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations. PMID- 26674677 TI - Establishment of an Agrobacterium-mediated Inoculation System for Cucumber Green Mottle Mosaic Virus. AB - The infectious full-length cDNA clones of Cucumber green mottle mosaic virus (CGMMV) isolates KW and KOM, which were isolated from watermelon and oriental melon, respectively, were constructed under the control of the cauliflower mosaic virus 35S promoter. We successfully inoculated Nicotiana benthamiana with the cloned CGMMV isolates KW and KOM by Agrobacterium-mediated infiltration. Virulence and symptomatic characteristics of the cloned CGMMV isolates KW and KOM were tested on several indicator plants. No obvious differences between two cloned isolates in disease development were observed on the tested indicator plants. We also determined full genome sequences of the cloned CGMMV isolates KW and KOM. Sequence comparison revealed that only four amino acids (at positions 228, 699, 1212, and 1238 of the replicase protein region) differ between the cloned isolates KW and KOM. A previous study reported that the isolate KOM could not infect Chenopodium amaranticolor, but the cloned KOM induced chlorotic spots on the inoculated leaves. When compared with the previously reported sequence of the original KOM isolate, the cloned KOM contained one amino acid mutation (Ala to Thr) at position 228 of the replicase protein, suggesting that this mutation might be responsible for induction of chlorotic spots on the inoculated leaves of C. amaranticolor. PMID- 26674678 TI - Community shift of biofilms developed in a full-scale drinking water distribution system switching from different water sources. AB - The bacterial community of biofilms in drinking water distribution systems (DWDS) with various water sources has been rarely reported. In this research, biofilms were sampled at three points (A, B, and C) during the river water source phase (phase I), the interim period (phase II) and the reservoir water source phase (phase III), and the biofilm community was determined using the 454 pyrosequencing method. Results showed that microbial diversity declined in phase II but increased in phase III. The primary phylum was Proteobacteria during three phases, while the dominant class at points A and B was Betaproteobacteria (>49%) during all phases, but that changed to Holophagae in phase II (62.7%) and Actinobacteria in phase III (35.6%) for point C, which was closely related to its water quality. More remarkable community shift was found at the genus level. In addition, analysis results showed that water quality could significantly affect microbial diversity together, while the nutrient composition (e.g. C/N ration) of the water environment might determine the microbial community. Furthermore, Mycobacterium spp. and Pseudomonas spp. were detected in the biofilm, which should give rise to attention. This study revealed that water source switching produced substantial impact on the biofilm community. PMID- 26674679 TI - Hepatotoxicity and nephrotoxicity induced by the chlorpyrifos and chlorpyrifos methyl metabolite, 3,5,6-trichloro-2-pyridinol, in orally exposed mice. AB - 3,5,6-Trichloro-2-pyridinol (TCP) is a primary degradation product of chlorpyrifos and chlorpyrifos-methyl. TCP has longer half-life in soil and greater solubility in water than its parent compound, and cause wide contamination in environments. However, studies about the toxic effects of TCP are limited and outdate. In this study, 5 mg/kg/day, 50 mg/kg/day, and 150 mg/kg/day TCP were given to male mice through gavage for four weeks. As a result, the final body weights of TCP treated groups were significantly lower than control, and the relative organ weights of the liver and kidney were significantly higher than that of control. In addition, NMR-based metabolomics was used to investigate the toxic effects of TCP. It was found that a total of 39 serum metabolites were significantly changed in the TCP-treated groups, and these metabolites are related to hepatotoxicity and nephrotoxicity. These results were also confirmed by histopathology, serum biochemical, and oxidative stress analysis. In addition, metabolic disturbances due to TCP exposure were also observed based on altered metabolites. As far as we know, these results are the first to show the metabolomic toxicity of TCP, which warrants further research. PMID- 26674680 TI - Co-evolution of hydrological components under climate change scenarios in the Mediterranean area. AB - The Mediterranean area is historically characterized by high human pressure on water resources. Today, while climate is projected to be modified in the future, through precipitation decrease and temperature increase, that jointly and non linearly may affect runoff, concerns about water availability are increasing. For these reasons, quantitative assessment of future modifications in the mean annual water availability are important; likewise, the description of the future interannual variability of some hydrological components such as runoff and evapotranspiration are highly wished for water management and ecosystems dynamics analyses. This study investigates at basin spatial scale future runoff and evapotranspiration, exploring their probability density functions and their interdependence as functions of climatic changes. In order to do that, a parsimonious conceptual lumped model is here used. The model is forced by different future climate scenarios, generated through a weather generator based on a stochastic downscaling of an ensemble of General Circulation Models (GCMs) realizations. The use of the adopted hydrological model, under reliable stochastic future climate scenarios, allows to project future values of evapotranspiration and runoff in a probabilistic framework and, at the same time, the evaluation of their bivariate frequency distributions for changes through the Multivariate Kernel Density Estimation method. As a case study, a benchmark Mediterranean watershed has been proposed (Imera Meridionale, Italy). Results suggest a radical shift and shape modification of the annual runoff and evapotranspiration probability density functions. Possible implications and impacts on water resources management are here addressed and discussed. PMID- 26674671 TI - Global Assessment of Bisphenol A in the Environment: Review and Analysis of Its Occurrence and Bioaccumulation. AB - Because bisphenol A (BPA) is a high production volume chemical, we examined over 500 peer-reviewed studies to understand its global distribution in effluent discharges, surface waters, sewage sludge, biosolids, sediments, soils, air, wildlife, and humans. Bisphenol A was largely reported from urban ecosystems in Asia, Europe, and North America; unfortunately, information was lacking from large geographic areas, megacities, and developing countries. When sufficient data were available, probabilistic hazard assessments were performed to understand global environmental quality concerns. Exceedances of Canadian Predicted No Effect Concentrations for aquatic life were >50% for effluents in Asia, Europe, and North America but as high as 80% for surface water reports from Asia. Similarly, maximum concentrations of BPA in sediments from Asia were higher than Europe. Concentrations of BPA in wildlife, mostly for fish, ranged from 0.2 to 13 000 ng/g. We observed 60% and 40% exceedences of median levels by the US Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey in Europe and Asia, respectively. These findings highlight the utility of coordinating global sensing of environmental contaminants efforts through integration of environmental monitoring and specimen banking to identify regions for implementation of more robust environmental assessment and management programs. PMID- 26674681 TI - Coupling effects of abiotic and biotic factors on molecular composition of dissolved organic matter in a freshwater wetland. AB - In this study, temporal and spatial variations in five defined molecular size fractions of dissolved organic matter (DOM) were examined for a well preserved wetland (Upo Wetland) and its surrounding areas, and the influencing factors were explored with many biotic and abioic parameters. For each DOM sample, the five size fractions were determined by size-exclusion chromatography coupled with organic carbon detector (SEC-OCD). For 2-year long monthly monitoring, bio polymers (BP), humic substances (HS), building blocks (BB), low molecular-weight (LMW) neutrals, and LMW acids displayed the median values of 264, 1884, 1070, 1090, and 11 MUg-CL(-1), respectively, accounting for 6.2%, 41.7%, 24.5%, 26.4%, and 0.4% of dissolved organic carbon (DOC). The dominant presence of HS indicated that terrestrial input played important roles in DOM composition of the freshwater ecosystem, which contrasted with coastal wetlands in other reports. Both seasonal and periodic patterns in the variations were found only for HS and BB among the size fractions. It was also notable that the sources of HS were seasonally shifted from aquagenic origin in winter to pedogenic origin in summer. The correlations among the size fractions revealed that BB and LMW neutrals might be degradation products from HS and humic-like substances (HS+BB), respectively, while LMW acids, from LMW neutrals. Principle component analysis revealed that the humic-like substances and the aromaticity of DOM were associated with temperature, chlorophyll a, phosphorous, and rainfall, whereas the other fractions and the molecular weight of HS were primarily affected by solar irradiation. Significant correlations between DOM composition and some biotic factors further suggested that DOM may even affect the biological communities, which provides an insight into the potential coupling effects of biotic and abiotic factors on DOM molecular composition in freshwater wetlands. PMID- 26674682 TI - Organic pollutants profiling of wood ashes from biomass power plants linked to the ash characteristics. AB - PURPOSE: Wood ash, characterized by high content of certain nutrients and charcoal, can be applied to soils as a means of managing this waste product improving the soil quality. The associated environmental risk must be assessed. The objective of this study was to characterize the bottom and fly ash collected from 15 biomass power plants in Spain by determining the benzene, toluene, ethylbenzene, xylene and styrene (BTEX+S), PAHs and aliphatic hydrocarbon contents of both types of ash. Biochar was also used for comparison purposes. METHODS: Gas chromatography-mass spectrometric methods were used for the identification and determination of both BTEX+S and aliphatic hydrocarbon contents in bottom and fly ashes, as well as biochar. High performance liquid chromatography with fluorescence detection was used for PAHs measurements. Multivariate correlation analysis was used to determine the relationship between sample characteristics and pollutants identified by partial least squares regression analysis. RESULTS AND DISCUSSION: In general, the degree to which organic matter in the sample is burned increases with T50 or the "50% burn off" temperature (possibly due to the addition of fuel), and the BTEX+S also tended to increase. However, as the Q/MO (the heat of combustion divided by organic matter mass) increased, the combustion decreased or proceeded with less oxygen, which appears to be related to an increased presence of PAHs. The results confirm that the amounts of organic pollutants (PAHs and BTEX+S, together with total aliphatic hydrocarbons) in the wood ash do not exceed limits established for different soil or industrial uses. CONCLUSIONS: Both types of ash, together with biochar, may therefore be suitable for application to soil as a fertilizer and an organic amendment, taking into account the target organic pollutants. PMID- 26674683 TI - A 70-year perspective on tropical forest regeneration. AB - Forested areas of the world decreased by 129 million hectare during the past quarter-century, and only 35 % of remainder is primary forest. Secondary forests are therefore relatively more important for biodiversity conservation, catchment protection, climate control, and the ecological services they provide. Many governments expend large resources on afforestation projects, which may not be supported by objective data on rates and pathways of natural succession in secondary forest. This paper describes a 70-year succession of tropical forest in Hong Kong under different management regimes including afforestation programs, frequent fire, and fire protection. From complete destruction of its forest during the Second World War, forest has established rapidly in areas where a shrub cover was able to colonize. The practice of afforestation as a nursery stage on degraded hillsides, for establishment of forest seedlings by natural invasion is not supported by the evidence, as when the native Pinus massoniana plantations were eliminated by disease during the 1970s, no forest or woody species were seen in the areas affected. In fact there was a reversion to grassland, which persisted there for almost three decades, until recent shrub invasion. The fastest period of forest regeneration, at 10.9% annually between 1989 and 2001, occurred when shrubland edge was greatest and forest was able to colonize across interfluves between linear-shaped riparian shrublands in valley bottoms. After 2001, succession to forest was slower, at 7.8% annually, as forest patches consolidated and edge habitats reduced. Effective forest management policies could include seeding of native shrubs extending linearly from established forest, to maximize edge length between woody species and grasslands, and planting of late successional species in areas where forest pioneers are in decline. PMID- 26674684 TI - Assessment of contaminant fate in catchments using a novel integrated hydrobiogeochemical-multimedia fate model. AB - Models for pollution exposure assessment typically adopt an overly simplistic representation of geography, climate and biogeochemical processes. This strategy is unsatisfactory when high temporal resolution simulations for sub-regional spatial domains are performed, in which parameters defining scenarios can vary interdependently in space and time. This is, for example, the case when assessing the influence of biogeochemical processing on contaminant fate. Here we present INCA-Contaminants, the Integrated Catchments model for Contaminants; a new model that simultaneously and realistically solves mass balances of water, carbon, sediments and contaminants in the soil-stream-sediment system of catchments and their river networks as a function of climate, land use/management and contaminant properties. When forced with realistic climate and contaminant input data, the model was able to predict polychlorinated biphenyls (PCBs) concentrations in multiple segments of a river network in a complex landscape. We analyzed model output sensitivity to a number of hydro-biogeochemical parameters. The rate of soil organic matter mineralization was the most sensitive parameter controlling PCBs levels in river water, supporting the hypothesis that organic matter turnover rates will influence re-mobilization of previously deposited PCBs which had accumulated in soil organic matrix. The model was also used to project the long term fate of PCB 101 under two climate scenarios. Catchment diffuse run off and riverine transport were the major pathways of contaminant re mobilization. Simulations show that during the next decade the investigated boreal catchment will shift from being a net atmospheric PCB sink to a net source for air and water, with future climate perturbation having little influence on this trend. Our results highlight the importance of using credible hydro biogeochemical simulations when modeling the fate of hydrophobic contaminants. PMID- 26674685 TI - Using a tiered approach based on ecotoxicological techniques to assess the ecological risks of contamination in a subtropical estuarine protected area. AB - This study sought to assess the ecological risks of sediments from the northern portion of an estuarine protected area (Cananeia-Iguape-Peruibe Protected Area- CIP-PA). The CIP-PA is located on the southern coast of Sao Paulo State, Brazil and is influenced by former mining activities along the Ribeira de Iguape River (RIR). We used a tiered approach based on multiple lines of evidence (geochemical analyses, toxicity tests, and whole sediment toxicity identification and evaluation) in order to assess environmental quality. The sediments presented a heterogeneous composition, but the samples collected close to the RIR exhibited higher concentrations of metals (Cd, Cr, Cu, Pb) and toxicity. Multivariate analysis showed that toxicity was associated with metals, mud, organic matter, and CaCO3 quantities. The whole-sediment toxicity identification evaluation approach indicated that ammonia and metals were responsible for sediment toxicity. Overall, we concluded that the sediments collected at depositional areas from the northern portion of the CIP-PA presented high levels of metals, which originated from former mining areas located in the upper RIR basin, and that this contamination had toxic effects on aquatic invertebrates. The tiered approach was useful for identifying the degradation of sediment quality and also for indicating the causes of toxicity. Because the CIP-PA is an important estuarine protected area that is ecologically at risk, large-scale measures are required to control the sources of contamination. PMID- 26674686 TI - Estimating size and scope economies in the Portuguese water sector using the Bayesian stochastic frontier analysis. AB - This study aims to search for economies of size and scope in the Portuguese water sector applying Bayesian and classical statistics to make inference in stochastic frontier analysis (SFA). This study proves the usefulness and advantages of the application of Bayesian statistics for making inference in SFA over traditional SFA which just uses classical statistics. The resulting Bayesian methods allow overcoming some problems that arise in the application of the traditional SFA, such as the bias in small samples and skewness of residuals. In the present case study of the water sector in Portugal, these Bayesian methods provide more plausible and acceptable results. Based on the results obtained we found that there are important economies of output density, economies of size, economies of vertical integration and economies of scope in the Portuguese water sector, pointing out to the huge advantages in undertaking mergers by joining the retail and wholesale components and by joining the drinking water and wastewater services. PMID- 26674687 TI - Patterns and possible mechanisms of soil CO2 uptake in sandy soil. AB - It has been reported that soils in drylands can absorb CO2, although the patterns and mechanisms of such a process remain under debate. To address this, we investigated the relationships between soil CO2 flux and meteorological factors and soil properties in Northwest China to reveal the reasons for "anomalous" soil CO2 flux in a desert ecosystem. Soil CO2 flux increased significantly and exponentially with surficial turbulence at the diel scale under dry conditions (P<0.05), whereas the relationship under wet conditions was insignificant. Furthermore, soil CO2 flux demonstrated remarkable negative correlation with soil air pressure (P<0.05) in both dry and wet conditions. Analysis considering Henry's Law indicated that soil water content was insufficient to dissolve the absorbed CO2 in dry conditions, but was sufficient in wet conditions. The concentration of soil HCO3(-) in the morning was higher than in the evening in dry conditions, but this pattern was reversed in wet conditions. These results imply that CO2 outgassing induced by turbulence, expansion of soil air, CO2 effusion from soil water, and carbonate precipitation during daytime can explain the abiotic diurnal CO2 release. Moreover, CO2 pumping from the atmosphere into the soil, caused mainly by carbonate dissolution, can account for nocturnal CO2 absorption in dry conditions. The abiotic soil CO2 flux pattern (CO2 absorption throughout the diel cycle) in wet conditions can be attributed to downward mass flow of soil CO2 and intensified soil air shrinkage, CO2 dissolving in soil water, and carbonate dissolution. These results provide a basis for determining the location of abiotic fixed carbon within soils in desert ecosystems. PMID- 26674688 TI - Perfluorinated carboxylic acids in human breast milk from Spain and estimation of infant's daily intake. AB - Human milk samples were collected from 67 mothers in 2014 at a Primary Care Centre in Murcia (Spain) and analyzed for perfluorinated carboxylic acids (PFCAs). Concentrations measured for perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorododecanoic acid (PFDoDA) ranged from = 90th percentile of DTR. RESULTS: Risk of mortality on high DTR days was associated with age 75-84 years (odds ratio 1.07; 95% confidence interval 1.01-1.14) and >= 85 years (1.16; 1.08-1.24) as compared with age <= 64 years. The risk of the association was less for the Dai ethnic minority than Chinese Han (0.85; 0.75-0.96). Farmers (1.08; 1.03-1.14) and people with hypertension (1.09; 1.02-1.16) showed greater risk of dying on high DTR days than non-farmers and people without hypertension, respectively. Compared with "other" mortality causes, the risk was greater with cardiovascular causes (1.09; 1.04 1.15), notably ischemic heart disease (1.16; 1.08-1.25) and myocardial infarction (1.18; 1.08-1.29) in heart disease (1.11; 1.04-1.17), and ischemic stroke (1.17; 1.06-1.28) in stroke deaths (1.09; 1.03-1.15), as well as chronic bronchitis (1.22; 1.11-1.33) and chronic obstructive pulmonary disease (1.12; 1.05-1.20) in respiratory deaths (1.11; 1.04-1.18). CONCLUSIONS: Individual characteristics and specific mortality causes can modify the association of high DTR and mortality. This knowledge may help in better targeting the vulnerable populations and developing more effective intervention strategies. PMID- 26674693 TI - Reactivity of vinca alkaloids during water chlorination processes: Identification of their disinfection by-products by high-resolution quadrupole-Orbitrap mass spectrometry. AB - Concerns about the presence of anticancer drugs in the environment are rapidly increasing mainly due to their growing use in the developed countries and their known cytotoxic effects. Vinca alkaloids are widely used in cancer therapy; however, very scarce information is available on their occurrence, environmental fate and toxicological effects on aquatic organisms. Even less attention has been paid to their potential transformation products, which can exert higher toxicity than the parent compounds. Thus, in the present work, the reactivity of vincristine, vinblastine, vinorelbine and its metabolite 4-O-deacetyl vinorelbine during water chlorination processes has been investigated for the first time. Under the studied chlorination conditions, vincristine was fairly stable whereas vinblastine, vinorelbine and 4-O-deacetyl vinorelbine were quickly degraded. A total of sixty-five disinfection by-products were tentatively identified by ultra high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Among them, twenty by-products corresponded to mono-chlorinated compounds, eight to di-chlorinated compounds and two to tri-chlorinated compounds, which may be of major environmental concern. Other disinfection by-products involved hydroxylation and oxidation reactions. Although the structures of these by-products could not be positively confirmed due to lack of commercial standards, their chemical formulas and product ions can be added to databases, which will allow their screening in future monitoring studies. PMID- 26674694 TI - Geo-climatic heterogeneity in self-reported asthma, allergic rhinitis and chronic bronchitis in Italy. AB - BACKGROUND: Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases. AIM: To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy. METHODS: Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20-44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta regression models. RESULTS: 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I(2)=59.5%, p=0.022) and CB (I(2)=60.5%, p=0.019), but not in that of asthma like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p=0.017), but not with differences in the topographic one. CONCLUSIONS: Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean climates, and lower in rainy-cold northern climates. PMID- 26674695 TI - Exposure of children to arsenic in drinking water in the Tharparkar region of Sindh, Pakistan. AB - Humans can be exposed to arsenic (As) through air, drinking water, and food. The aim of this study was to calculate the hazard quotient (HQ) of As, based on its concentration in drinking water and the scalp hair of children (males) belonging to two age groups (5-10 and 11-14 years) who consumed water contaminated with different concentrations of As. The water samples were collected from As-exposed and nonexposed areas, which were classified as low-exposed (LE), high-exposed (HE), and nonexposed (NE) areas. The total concentration of inorganic As (iAs) and its species (As(III) and As(V)) in water samples of all selected areas was determined by advanced extraction methods. For purposes of comparison, the total As level was also determined in all water samples. The resulting data indicated that the predominant inorganic As species in groundwater samples was arsenate (As(V)). The As concentrations in drinking water of LE and HE areas were found to be 2.6-230-fold higher than the permissible limit for drinking water established by the World Health Organization (2004). However, the As levels in drinking water of the NE area was within the permissible limit (<10 MUg/L). The As levels in the scalp hair samples from boys of NE, LE, and HE areas ranged from 0.16 to 0.36, 0.36 to 0.83, and 11.5 to 31.9 mg/kg, respectively. A significant, positive correlation was observed between the As levels in drinking water and scalp hair samples of children from the HE area, compared with the other two groups (p>0.01). The As toxicity risk assessment based on HQ for the NE, LE, and HE areas corresponded to <10, >= 10, and >10, respectively. These HQ values indicated the noncarcinogenic, less carcinogenic, and highly carcinogenic exposure risks faced by children from the NE, LE, and HE areas, respectively. It can be concluded that children consuming the groundwater of the LE (Khairpur Mir's) and HE (Tharparkar) areas of Pakistan are at a potential risk of chronic As toxicity. PMID- 26674696 TI - Contamination of phthalate esters, organochlorine pesticides and polybrominated diphenyl ethers in agricultural soils from the Yangtze River Delta of China. AB - To reveal the pollution status associated with rapid urbanization and economic growth, extensive areas of agricultural soils (approximately 45,800 km(2)) in the Yangtze River Delta of China were investigated with respect to selected endocrine disruptor compounds (EDCs), including phthalate esters (PAEs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). The residues of sum of 15 PAEs, sum of 15 OCPs and sum of 13 PBDEs were in the range of 167-9370 ng/g, 1.0-3520 ng/g, and <1.0-382 ng/g, respectively. The OCPs residuals originated from both historical usage and recent input. Agricultural plastic film was considered to be an important source of PAEs. Discharge from furniture industry was potential major source of PBDEs in this region. The selected pollutants showed quite different spatial distributions within the studied region. It is worth noting that much higher concentrations of the EDCs were found on the borders between Shanghai and the two neighboring provinces, where agriculture and industry developed rapidly in recent years. Contaminants from both agricultural and industrial activities made this area a pollution hotspot, which should arouse more stringent regulation to safeguard the environment and food security. PMID- 26674697 TI - Fingerprinting two metal contaminants in streams with Cu isotopes near the Dexing Mine, China. AB - Transition metal isotope signatures are becoming useful for fingerprinting sources in surface waters. This study explored the use of Cu isotope values to trace dissolved metal contaminants in stream water throughout a watershed affected by mining by-products of the Dexing Mine, the largest porphyry Cu operation in Asia. Cu isotope values of stream water were compared to potential mineral sources of Cu in the mining operation, and to proximity to the known Cu sources. The first mineral source, chalcopyrite, CuFeS2 has a 'tight' cluster of Cu isotope values (-0.150/00 to +1.650/00; +0.37 +/- 0.60/00, 1sigma, n=10), and the second mineral source, pyrite (FeS2), has a much larger range of Cu isotope values (-40/00 to +11.90/00; 2.7 +/- 4.30/00, 1sigma, n=16). Dissolved Cu isotope values of stream water indicated metal derived from either chalcopyrite or pyrite. Above known Cu mineralization, stream waters are approximately +1.50/00 greater than the average chalcopyrite and are interpreted as derived from weathering of chalcopyrite. In contrast, dissolved Cu isotope values in stream water emanating from tailings piles had Cu isotope values similar to or greater than pyrite (>+60/00, a common mineral in the tailings). These values are interpreted as sourced from the tailings, even in solutions that possess significantly lower concentrations of Cu (<0.05 ppm). Elevated Cu isotope values were also found in two soil and two tailings samples (delta(65)Cu ranging between +2 to +50/00). These data point to the mineral pyrite in tailings as the mineral source for the elevated Cu isotope values. Therefore, Cu isotope values of waters emanating from a clearly contaminated drainage possess different Cu isotope values, permitting the discrimination of Cu derived from chalcopyrite and pyrite in solution. Data demonstrate the utility of Cu isotopic values in waters, minerals, and soils to fingerprint metallic contamination for environmental problems. PMID- 26674698 TI - Shifts in the suitable habitat available for brown trout (Salmo trutta L.) under short-term climate change scenarios. AB - The impact of climate change on the habitat suitability for large brown trout (Salmo trutta L.) was studied in a segment of the Cabriel River (Iberian Peninsula). The future flow and water temperature patterns were simulated at a daily time step with M5 models' trees (NSE of 0.78 and 0.97 respectively) for two short-term scenarios (2011-2040) under the representative concentration pathways (RCP 4.5 and 8.5). An ensemble of five strongly regularized machine learning techniques (generalized additive models, multilayer perceptron ensembles, random forests, support vector machines and fuzzy rule base systems) was used to model the microhabitat suitability (depth, velocity and substrate) during summertime and to evaluate several flows simulated with River2D(c). The simulated flow rate and water temperature were combined with the microhabitat assessment to infer bivariate habitat duration curves (BHDCs) under historical conditions and climate change scenarios using either the weighted usable area (WUA) or the Boolean-based suitable area (SA). The forecasts for both scenarios jointly predicted a significant reduction in the flow rate and an increase in water temperature (mean rate of change of ca. -25% and +4% respectively). The five techniques converged on the modelled suitability and habitat preferences; large brown trout selected relatively high flow velocity, large depth and coarse substrate. However, the model developed with support vector machines presented a significantly trimmed output range (max.: 0.38), and thus its predictions were banned from the WUA based analyses. The BHDCs based on the WUA and the SA broadly matched, indicating an increase in the number of days with less suitable habitat available (WUA and SA) and/or with higher water temperature (trout will endure impoverished environmental conditions ca. 82% of the days). Finally, our results suggested the potential extirpation of the species from the study site during short time spans. PMID- 26674700 TI - Environmental impact assessment of wood ash utilization in forest road construction and maintenance--A field study. AB - The ever increasing use of wood material as fuel for green energy production requires innovative, environmentally safe strategies for recycling of the remaining wood ash. Utilizing wood ash in forest road construction and maintenance to improve mechanical stability has been suggested as a feasible recycling option. To investigate the environmental impact of wood ash application in forest road maintenance, a two-year field experiment was conducted at two Austrian forest sites (Kobernausserwald (KO) (soil pH 5.5) and Weyregg (WE) (pH 7.7)) differing in their soil chemical properties. Two different ashes, one produced by grate incineration (GA) and the other by fluidized bed incineration in a mixture with 15 vol% burnt lime (FBA), were incorporated in repeated road sections at a 15:85% (V/V) ash-to-soil rate. Leaching waters from the road body were collected and analyzed for 32 environmentally relevant parameters over two years. Upon termination of the experiment, sub-road soil samples were collected and analyzed for ash-related changes in soil chemistry. Even though a larger number of parameters was affected by the ash application at the alkaline site (WE), we observed the most pronounced initial increases of pH as well as Al, As, Fe, Mn, Ni, Co, Cu, Mo, and NO2(-) concentrations in leachates beneath GA-treated road bodies at Kobernausserwald due to the lower soil buffer capacity at this site. Despite the observed effects our results indicate that, when specific requirements are met (i.e. appropriate ash quality, sufficient soil buffer capacity below the road body, and single time-point ash incorporation within several decades), wood ash application in forest road construction is generally environmentally acceptable. PMID- 26674699 TI - Assessing arsenic exposure in households using bottled water or point-of-use treatment systems to mitigate well water contamination. AB - There is little published literature on the efficacy of strategies to reduce exposure to residential well water arsenic. The objectives of our study were to: 1) determine if water arsenic remained a significant exposure source in households using bottled water or point-of-use treatment systems; and 2) evaluate the major sources and routes of any remaining arsenic exposure. We conducted a cross-sectional study of 167 households in Maine using one of these two strategies to prevent exposure to arsenic. Most households included one adult and at least one child. Untreated well water arsenic concentrations ranged from <10 MUg/L to 640 MUg/L. Urine samples, water samples, daily diet and bathing diaries, and household dietary and water use habit surveys were collected. Generalized estimating equations were used to model the relationship between urinary arsenic and untreated well water arsenic concentration, while accounting for documented consumption of untreated water and dietary sources. If mitigation strategies were fully effective, there should be no relationship between urinary arsenic and well water arsenic. To the contrary, we found that untreated arsenic water concentration remained a significant (p <= 0.001) predictor of urinary arsenic levels. When untreated water arsenic concentrations were <40 MUg/L, untreated water arsenic was no longer a significant predictor of urinary arsenic. Time spent bathing (alone or in combination with water arsenic concentration) was not associated with urinary arsenic. A predictive analysis of the average study participant suggested that when untreated water arsenic ranged from 100 to 500 MUg/L, elimination of any untreated water use would result in an 8%-32% reduction in urinary arsenic for young children, and a 14%-59% reduction for adults. These results demonstrate the importance of complying with a point-of-use or bottled water exposure reduction strategy. However, there remained unexplained, water related routes of exposure. PMID- 26674701 TI - Short and long term biosorption of silica-coated iron oxide nanoparticles in heterotrophic biofilms. AB - The increased application of engineered nanoparticles (ENP) in industrial processes and consumer products has raised concerns about their impact on health and environmental safety. When ENP enter the global water cycle by e.g. wastewater streams, wastewater treatment plants (WWTP) represent potential sinks for ENP. During biological WWT, the attachment of ENP to biofilms is responsible for the desired removal of ENP from the water phase avoiding their release into the aquatic environment. However, the fundamental mechanisms guiding the interactions between ENP and biofilms are not yet fully understood. Therefore, this study investigates the behavior and biosorption of inorganic ENP, here magnetic iron oxide nanoparticles coated with silica (scFe3O4-NP), with heterotrophic biofilms at different time scales. Their magnetic properties enable to follow scFe3O4-NP in the biofilm system by a magnetic susceptibility balance and magnetic resonance imaging. Biofilms were exposed to scFe3O4-NP at short contact times (5 min) in flow cells and complementary, scFe3O4-NP were introduced into a moving bed biofilm reactor (MBBR) to be observed for 27 d. Mass balances revealed that scFe3O4-NP sorbed to the biofilm within a few minutes, but that the total biosorption was rather low (3.2 MUg Fe/mg TSS). scFe3O4-NP mainly sorbed to the biofilm surface inducing the detachment of outer biofilm parts starting after an exposure time of 3h in the MBBR. The biosorption depended on the exposure concentration of scFe3O4-NP, but less on the contact time. Most scFe3O4-NP exited the flow cell (up to 65%) and the MBBR (57%) via the effluent. This effect was favored by the stabilization of scFe3O4-NP in the bulk liquid by organic matter leading to a low retention capacity of the MBBR system. The results contribute to improve our understanding about the fate of ENP in environmental and in technical biofilm systems and give indications for future investigations needed. PMID- 26674702 TI - Influences upon the lead isotopic composition of organic and mineral horizons in soil profiles from the National Soil Inventory of Scotland (2007-09). AB - Some 644 individual soil horizons from 169 sites in Scotland were analyzed for Pb concentration and isotopic composition. There were three scenarios: (i) 36 sites where both top and bottom (i.e. lowest sampled) soil horizons were classified as organic in nature, (ii) 67 with an organic top but mineral bottom soil horizon, and (iii) 66 where both top and bottom soil horizons were mineral. Lead concentrations were greater in the top horizon relative to the bottom horizon in all but a few cases. The top horizon (206)Pb/(207)Pb ratio was lesser (outside analytical error) than the corresponding bottom horizon (206)Pb/(207)Pb ratio at (i) 64%, (ii) 94% and (iii) 73% of sites, and greater at only (i) 8%, (ii) 3% and (iii) 8% of sites. A plot of (208)Pb/(207)Pb vs. (208)Pb/(206)Pb ratios showed that the Pb in organic top (i, ii) and bottom (i) horizons was consistent with atmospherically deposited Pb of anthropogenic origin. The (206)Pb/(207)Pb ratio of the organic top horizon in (ii) was unrelated to the (206)Pb/(207)Pb ratio of the mineral bottom horizon as demonstrated by the geographical variation in the negative shift in the ratio, a result of differences in the mineral horizon values arising from the greater influence of radiogenic Pb in the north. In (iii), the lesser values of the (206)Pb/(207)Pb ratio for the mineral top horizon relative to the mineral bottom horizon were consistent with the presence of anthropogenic Pb, in addition to indigenous Pb, in the former. Mean anthropogenic Pb inventories of 1.5 and 4.5 g m(-2) were obtained for the northern and southern halves of Scotland, respectively, consistent with long-range atmospheric transport of anthropogenic Pb (mean (206)Pb/(207)Pb ratio~1.16). For cultivated agricultural soils (Ap), this corresponded to about half of the total Pb inventory in the top 30 cm of the soil column. PMID- 26674703 TI - Modelling the impact of land subsidence on urban pluvial flooding: A case study of downtown Shanghai, China. AB - This paper presents a numerical analysis of pluvial flooding to evaluate the impact of land subsidence on flood risks in urban contexts using a hydraulic model (FloodMap-HydroInundation2D). The pluvial flood event of August 2011 in Shanghai, China is used for model calibration and simulation. Evolving patterns of inundation (area and depth) are assessed over four time periods (1991, 1996, 2001 and 2011) for the downtown area, given local changes in topography and rates of land subsidence of up to 27 mm/yr. The results show that land subsidence can lead to non-linear response of flood characteristics. However, the impact on flood depths is generally minor (<5 cm) and limited to areas with lowest-lying topographies because of relatively uniform patterns of subsidence and micro topographic variations at the local scale. Nonetheless, the modelling approach tested here may be applied to other cities where there are more marked rates of subsidence and/or greater heterogeneity in the depressed urban surface. In these cases, any identified hot-spots of subsidence and focusing of pluvial flooding may be targeted for adaptation interventions. PMID- 26674704 TI - Wide range of metallic and organic contaminants in various tissues of the Antarctic prion, a planktonophagous seabird from the Southern Ocean. AB - Trace elements (n=14) and persistent organic pollutants (POPs, n=30) were measured in blood, liver, kidney, muscle and feathers of 10 Antarctic prions (Pachyptila desolata) from Kerguelen Islands, southern Indian Ocean, in order to assess their concentrations, tissue distribution, and inter-tissue and inter contaminant relationships. Liver, kidney and feathers presented the highest burdens of arsenic, cadmium and mercury, respectively. Concentrations of cadmium, copper, iron, and zinc correlated in liver and muscle, suggesting that uptake and pathways of metabolism and storage were similar for these elements. The major POPs were 4,4'-DDE, mirex, PCB-153 and PCB-138. The concentrations and tissue distribution patterns of environmental contaminants were overall in accordance with previous results in other seabirds. Conversely, some Antarctic prions showed surprisingly high concentrations of BDE-209. This compound has been rarely observed in seabirds before, and its presence in Antarctic prions could be due to the species feeding habits or to the ingestion of plastic debris. Overall, the study shows that relatively lower trophic level seabirds (zooplankton-eaters) breeding in the remote southern Indian Ocean are exposed to a wide range of environmental contaminants, in particular cadmium, selenium and some emerging POPs, which merits further toxicological investigations. PMID- 26674705 TI - Properties of plant nutrient: Comparison of two nutrient recovery techniques using liquid fraction of digestate from anaerobic digester treating pig manure. AB - Anaerobic digestate has valuable potential as organic fertilizer or soil amendment, given that it typically contains high amounts of plant nutrients, such as nitrogen, phosphate and plant hormones. In this study, ammonia stripping and vacuum evaporation were tested to compare their technical feasibilities and their effects on plant nutrient properties in the liquid fraction of digestate. Results of the batch experiments showed that the nutrient characteristics of liquid digestate, including total ammonia nitrogen (TAN), soluble P, gibberellic acid (GA), indoleacetic acid (IAA) and abscisic acid (ABA), were strongly dependent on the initial pH in both ammonia stripping and vacuum evaporation processes. A low plant nutrient concentration (TAN 137 mg . L(-1), soluble P 1.5 mg . L(-1), GA3/ABA 0.04) in the liquid digestate was achieved in the ammonia stripping process with Ca(OH)2 addition of 12 g . L(-1), whereas a high nutrient concentration (TAN 2998 mg . L(-1), soluble P 178.3 mg . L(-1), IAA 60.9 mg . L( 1) and GA3/ABA 0.4) was achieved in vacuum evaporation at a pH level of 6. According to the results, both ammonia stripping and vacuum evaporation can be used as an alternative of nutrient recovery techniques, which should be chosen based on the potential different applications of liquid digestate (e.g., soaking seed, increasing plant tolerance, and nutrients transportation). PMID- 26674706 TI - Passive samplers accurately predict PAH levels in resident crayfish. AB - Contamination of resident aquatic organisms is a major concern for environmental risk assessors. However, collecting organisms to estimate risk is often prohibitively time and resource-intensive. Passive sampling accurately estimates resident organism contamination, and it saves time and resources. This study used low density polyethylene (LDPE) passive water samplers to predict polycyclic aromatic hydrocarbon (PAH) levels in signal crayfish, Pacifastacus leniusculus. Resident crayfish were collected at 5 sites within and outside of the Portland Harbor Superfund Megasite (PHSM) in the Willamette River in Portland, Oregon. LDPE deployment was spatially and temporally paired with crayfish collection. Crayfish visceral and tail tissue, as well as water-deployed LDPE, were extracted and analyzed for 62 PAHs using GC-MS/MS. Freely-dissolved concentrations (Cfree) of PAHs in water were calculated from concentrations in LDPE. Carcinogenic risks were estimated for all crayfish tissues, using benzo[a]pyrene equivalent concentrations (BaPeq). ?PAH were 5-20 times higher in viscera than in tails, and ?BaPeq were 6-70 times higher in viscera than in tails. Eating only tail tissue of crayfish would therefore significantly reduce carcinogenic risk compared to also eating viscera. Additionally, PAH levels in crayfish were compared to levels in crayfish collected 10 years earlier. PAH levels in crayfish were higher upriver of the PHSM and unchanged within the PHSM after the 10-year period. Finally, a linear regression model predicted levels of 34 PAHs in crayfish viscera with an associated R-squared value of 0.52 (and a correlation coefficient of 0.72), using only the Cfree PAHs in water. On average, the model predicted PAH concentrations in crayfish tissue within a factor of 2.4 +/- 1.8 of measured concentrations. This affirms that passive water sampling accurately estimates PAH contamination in crayfish. Furthermore, the strong predictive ability of this simple model suggests that it could be easily adapted to predict contamination in other shellfish of concern. PMID- 26674707 TI - Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4. AB - Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) are commonly used for treating major depression. Regretfully, significant heterogeneity exists regarding the benefits of SSRI/SNRI in individual cases. We previously reported that a polymorphism located in the serotonin transporter linked promoter region (5-HTT LPR) is associated with an interindividual difference in SSRI treatment efficacy. However, this explains only a small part of the variation of this complex phenotype. Other 5-HTT variants in the coding regions, 3' untranslated region (3' UTR), and introns adjacent to each exon could also contribute to treatment response. Therefore, we performed a sequencing analysis of the SLC6A4 gene (coding for 5-HTT) and investigated the association between variants detected in this study and the antidepressant response to SSRI/SNRI in 201 Japanese depressive patients. Seventeen novel mutations were identified by sequencing analysis. We found that the polymorphism G2563T (rs3813034) as a tag single-nucleotide polymorphism of IVS9 A-90G (rs140701), G2356T (rs1042173), and A3641C (rs7224199) is associated with interindividual variability of SSRI/SNRI efficacy at week 6, independent from clinical variables and effect of 5-HTT LPR (P < 0.001 by multiple regression analysis). This polymorphism could help determine individualized SSRI/SNRI treatments for depressive patients in combination with 5-HTT LPR. PMID- 26674709 TI - Spectrum of Sinonasal Tumors: A 10-year Experience at a Tertiary Care Hospital in North India. AB - OBJECTIVE: Sinonasal tumors are a highly heterogeneous group of tumors that account for less than 1% of all cancers. Precise diagnosis is essential because the natural history, treatment, and prognosis vary for different neoplasms. We reviewed 610 cases of sinonasal lesions to understand this entity better. METHODS: A total of 610 sinonasal biopsies/specimens were received over a period of 10 years (2004-14). All the samples were processed and stained with hematoxylin and eosin. Special staining for microorganisms and immunohistochemistry were performed where indicated. RESULTS: Benign lesions were 72% with nasal polyp being the most common. Malignant lesions made up 21.2% of lesions with nasopharyngeal carcinoma being the most common while 7.7% cases were inflammatory/non-neoplastic. The most common cause for this was fungal sinusitis. The maxillary sinus was the most frequently involved site in all the lesions (62%). The average age of presentation was 40 years old, and the male to female ratio was 3:1 in those with benign tumors. The average age of presentation in the malignant and inflammatory group were 45 and 43 years, respectively, with an almost equal sex ratio in both categories. Computed tomography and magnetic resonance imaging scans were done in virtually all cases to assess the extent of the tumor as well as bony destruction. Local recurrence was the most frequent cause of treatment failure. CONCLUSION: Tumors of the nasal cavity are often grouped with those in the paranasal sinuses. Benign tumors constituted approximately 75% of tumors in our hospital. Squamous cell carcinoma was the most common malignancy of this region. These tumors need to be studied closely and accurately because their proximity to vital structures pose significant challenges for their treatment and may be the source of significant patient morbidity. PMID- 26674708 TI - Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation. AB - Both chemical and mechanical stimuli can dramatically influence cell behavior. By optimizing the signals cells experience, it may be possible to control the behavior of therapeutic cell populations. In this work, biomimetic geometries of adhesive ligands, which recapitulate the morphology of mature cells, are used to direct human mesenchymal stem cell (HMSC) differentiation toward a desired lineage. Specifically, adipocytes cultured in 2D are imaged and used to develop biomimetic virtual masks used in laser scanning lithography to form patterned fibronectin surfaces. The impact of adipocyte-derived pattern geometry on HMSC differentiation is compared to the behavior of HMSCs cultured on square and circle geometries, as well as adipocyte-derived patterns modified to include high stress regions. HMSCs on adipocyte mimetic geometries demonstrate greater adipogenesis than HMSCs on the other patterns. Greater than 45% of all HMSCs cultured on adipocyte mimetic patterns underwent adipogenesis as compared to approximately 19% of cells on modified adipocyte patterns with higher stress regions. These results are attributed to variations in cytoskeletal tension experienced by cells on the different protein micropatterns. The effects of geometry on adipogenesis are mitigated by the incorporation of a cytoskeletal protein inhibitor; exposure to this inhibitor leads to increased adipogenesis on all patterns examined. PMID- 26674710 TI - Ultrasonographic diagnostics of pain in the lateral cubital compartment and proximal forearm. AB - Pain in the lateral compartment of the elbow joint and decreased strength of the extensor muscle constitute a fairly common clinical problem. These symptoms, occurring in such movements as inverting and converting the forearm, pushing, lifting and pulling, mostly affect people who carry out daily activities with an intense use of wrist, e.g. work on computer. Strains in this area often result from persistent overload and degeneration processes of the common extensor tendon and the radial collateral ligament. Similar symptoms resulting from the compression of deep branch of the radial nerve in radial nerve tunnel should be remembered as well. It happens that both conditions occur simultaneously. A proper diagnosis is essential in undertaking an effective treatment. Ultrasonography is a non-invasive method and the application of high-end apparatus with heads of frequencies exceeding 12 MHz allows for a precise evaluation of joint structures, tendons and nerves. In case of the so-called tennis elbow, the examination allows for evaluation of the degree and extent of injury to the radial collateral ligament and common extensor tendon, in addition to the presence of blood vessels in inflicted area. Administration of autologous blood platelets concentrate containing growth factors, used in treatment of tennis elbow, is performed under ultrasound image control conditions. This allows for a precise incision of scar whilst keeping a healthy (unaffected) tissue margin to form fine channels enabling the penetration of growth factors. Post surgery medical check-up allows for the evaluation of treatment effectiveness. In radial nerve tunnel syndrome, the ultrasound examination can reveal abnormalities in the deep branch of the radial nerve and within the anatomical structures adjacent to the nerve in the radial nerve tunnel. Furthermore, the ultrasound examination allows for detection of other articular and extraarticular pathologies, which affect the compression of the deep branch of radial nerve, such as skeletal deformations, post-traumatic changes, arthritis, and the presence of tumors. The ultrasonography is also helpful in differentiation of symptoms arising from cervical radiculopathy or brachial plexus injury. PMID- 26674711 TI - Prevalence of Multidrug Resistant Pulmonary Tuberculosis in North Bihar. AB - INTRODUCTION: Multidrug resistant tuberculosis (MDR-TB) is caused by Infection with Mycobacterium tuberculosis which is resistant to both isoniazid (INH) and rifampicin (RIF), with or without any other anti tubercular drug. It is caused by resistant mutant strains due to inadequate treatment and poor compliance. Due to time taking conventional diagnostic methods, drug resistant strains continue to spread. Therefore rapid diagnosis and treatment of MDR-TB strains are prerequisites for the worldwide fight against TB. OBJECTIVE: To determine the prevalence of MDR TB in North Bihar by molecular diagnostic method and to facilitate early diagnosis and treatment. Also, to find out the number of those diagnosed cases who were successfully initiated the treatment in MDR TB Centre of DMCH. MATERIALS AND METHODS: This six month observational study was carried out in IRL Darbhanga, Damien TB research Centre of the Darbhanga Medical College and Hospital, Bihar, India. During the period of February-July 2014, 256 sputum samples were collected from suspected cases of multidrug resistant tuberculosis, from 6 districts of North Bihar around Darbhanga. These samples were subjected to routine microscopy and culture to detect Mycobacterium tuberculosis. Positive cases were subjected to drug sensitivity test by a molecular diagnostic method, Using Genotype MTBDR plus kit. RESULT: Out of 256 sputum samples from suspected cases of MDR TB, 122 cases were microscopy positive for tuberculosis. Among these 122 cases, tuberculosis was confirmed by PCR in 114 cases. Finally with the help of Line Probe Assay (LPA), 39(15%) samples were found to have resistance to both INH and Rifampicin. Male female ratio was 4:1. CONCLUSION: The Prevalence of Multi drug resistant pulmonary tuberculosis in North Bihar is 15%. It needs early diagnosis by molecular diagnostic method and prompt treatment to reduce the spread of MDR TB cases. PMID- 26674712 TI - In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes. AB - Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1-200 MUg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2-10.8 mg/m(3)) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the gamma-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1-200 MUg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m(3)). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 MUg/cm(2)), while MWCNT-T increased strand breakage only at 200 MUg/cm(2). Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs. PMID- 26674722 TI - Editorial: Improving the data reproducibility and general interest of natural product submissions. PMID- 26674723 TI - Corrigendum: Training-induced alterations of skeletal muscle mitochondrial biogenesis proteins in non-insulin-dependent type 2 diabetic men. PMID- 26674724 TI - Determinants of mastitis in women in the CASTLE study: a cohort study. AB - BACKGROUND: Mastitis is an acute, debilitating condition that occurs in approximately 20 % of breastfeeding women who experience a red, painful breast with fever. This paper describes the factors correlated with mastitis and investigates the presence of Staphylococcus aureus in women who participated in the CASTLE (Candida and Staphylococcus Transmission: Longitudinal Evaluation) study. The CASTLE study was a prospective cohort study which recruited nulliparous women in late pregnancy in two maternity hospitals in Melbourne, Australia in 2009-2011. METHODS: Women completed questionnaires at recruitment and six time-points in the first eight weeks postpartum. Postpartum questionnaires asked about incidences of mastitis, nipple damage, milk supply, expressing practices and breastfeeding problems. Nasal and nipple swabs were collected from mothers and babies, as well as breast milk samples. All samples were cultured for S. aureus. "Time at risk" of mastitis was defined as days between birth and first occurrence of mastitis (for women who developed mastitis) and days between birth and the last study time-point (for women who did not develop mastitis). Risk factors for incidence of mastitis occurring during the time at risk (Incident Rate Ratios [IRR]) were investigated using a discrete version of the multivariable proportional hazards regression model. RESULTS: Twenty percent (70/346) of participants developed mastitis. Women had an increased risk of developing mastitis if they reported nipple damage (IRR 2.17, 95 % CI 1.21, 3.91), over-supply of breast milk (IRR 2.60, 95 % CI 1.58, 4.29), nipple shield use (IRR 2.93, 95 % CI 1.72, 5.01) or expressing several times a day (IRR 1.64, 95 % CI 1.01, 2.68). The presence of S. aureus on the nipple (IRR 1.72, 95 % CI 1.04, 2.85) or in milk (IRR 1.78, 95 % CI 1.08, 2.92) also increased the risk of developing mastitis. CONCLUSIONS: Nipple damage, over supply of breast milk, use of nipple shields and the presence of S. aureus on the nipple or in breast milk increased the mastitis risk in our prospective cohort study sample. Reducing nipple damage may help reduce maternal breast infections. PMID- 26674725 TI - Correlation of findings in clinical and high resolution ultrasonography examinations of the painful shoulder. AB - OBJECTIVE: High resolution ultrasonography is a non-painful and non-invasive imaging technique which is useful for the assessment of shoulder pain causes, as clinical examination often does not allow an exact diagnosis. The aim of this study was to compare the findings of clinical examination and high resolution ultrasonography in patients presenting with painful shoulder. METHODS: Non interventional observational study of 100 adult patients suffering from unilateral shoulder pain. Exclusion criteria were shoulder fractures, prior shoulder joint surgery and shoulder injections in the past month. The physicians performing the most common clinical shoulder examinations were blinded to the results of the high resolution ultrasonography and vice versa. RESULTS: In order to detect pathology of the m. supraspinatus tendon, the Hawkins and Kennedy impingement test showed the highest sensitivity (0.86) whereas the Jobe supraspinatus test showed the highest specificity (0.55). To identify m. subscapularis tendon pathology the Gerber lift off test showed a sensitivity of 1, whereas the belly press test showed the higher specificity (0.72). The infraspinatus test showed a high sensitivity (0.90) and specificity (0.74). All AC tests (painful arc II(a), AC joint tenderness(b), cross body adduction stress test(c)) showed high specificities ((a)0.96, (b)0.99, (c)0.96). Evaluating the long biceps tendon, the palm up test showed the highest sensitivity (0.47) and the Yergason test the highest specificity (0.88). CONCLUSION: Knowledge of sensitivity and specificity of various clinical tests is important for the interpretation of clinical examination test results. High resolution ultrasonography is needed in most cases to establish a clear diagnosis. PMID- 26674728 TI - A Plumbing Solution for Stem Cell-Derived Kidneys. PMID- 26674729 TI - Organ Trade: Knowledge, Awareness, and Nonlegislative Responses. PMID- 26674730 TI - Jose Medina Pestana, MD, PhD, FRCS: Head of Transplant Division. PMID- 26674731 TI - N-octanoyl Dopamine Attenuates the Development of Transplant Vasculopathy in Rat Aortic Allografts Via Smooth Muscle Cell Protective Mechanisms. AB - BACKGROUND: Transplant vasculopathy (TV) is a major cause for late graft loss after cardiac transplantation. Endothelial damage and T cell infiltration play a pivotal role in the development of TV. Because N-octanoyl dopamine (NOD) inhibits vascular inflammation and suppresses T cell activation in vitro, we here tested the hypothesis that NOD treatment ameliorates TV. METHODS: Aortic grafts were orthotopically transplanted in the Dark Agouti to Brown Norway strain combination. Recipient rats were treated with NOD or vehicle administered via osmotic minipumps. Histology and quantitative polymerase chain reaction (qPCR) were performed on nontransplanted aortas and grafts explanted 2 and 4 weeks after transplantation to assess the degree of TV, inflammation, apoptosis, and number of (proliferating) alpha smooth muscle actin (alphaSMA) neointimal cells. In vitro analyses of human aortic smooth muscle cells were performed to test the effect of NOD on proliferation (WST-1 assay), cell cycle (flow cytometry and qPCR), and cytokine-induced apoptosis (flow cytometry). RESULTS: Allografts from vehicle-treated recipients developed neointimal lesions predominantly consisting of alphaSMA-expressing cells. NOD treatment significantly reduced neointima formation and neointimal alphaSMA cells. In situ, smooth muscle cell proliferation (Ki67) was not influenced by NOD. Macrophage (CD68), T (CD3), and Natural Killer (ANK61) cell infiltration as well as intragraft TNFalpha and IFNgamma mRNA expression were similar in both groups. Medial apoptosis (cleaved caspase-3) was significantly reduced by NOD. In vitro, NOD inhibited proliferation of human aortic smooth muscle cells by causing a G1-arrest and protected from TNFalpha-induced apoptosis. CONCLUSIONS: This study identified NOD as potential treatment modality to attenuate TV. Our data clearly support a vasculoprotective effect of NOD by reducing smooth muscle cell proliferation and inflammation-induced apoptosis. PMID- 26674732 TI - Elevation of serum interleukins 8, 4, and 1beta levels in patients with gastrointestinal low-grade B-cell lymphoma. AB - Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P = 6.7E-05), IL-4 (P = 7.5E-05), and IL-1beta (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 beta levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development. PMID- 26674733 TI - Rare-earth metal bis(silylamide) complexes supported by mono-dentate arylamido ligand: synthesis, reactivity, and catalyst precursors in living cis-1,4 selective polymerization of isoprene. AB - The salt metathesis reaction of LnCl3 with 1 equivalent of arylamido lithium [2,6 (i)Pr2C6H3N(SiMe3)]Li followed by addition of 2 equivalents of LiN(SiHMe2)2 in THF at room temperature obtained neutral mono-arylamido-ligated rare-earth metal bis(silylamide) complexes [2,6-(i)Pr2C6H3N(SiMe3)]Ln[N(SiHMe2)2]2(THF) (Ln = Y (), Lu (), La ()) in good isolated yields. Treatment of with excess AlMe3 produced the mono(arylamido) Ln/Al heterotrinuclear methyl complexes [2,6 (i)Pr2C6H3N(SiMe3)]Ln[(MU-Me)2AlMe2]2 (Ln = Y (), Lu (), La ()) via amide-alkyl exchange. All these complexes were well-characterized by elemental analysis, NMR spectroscopy and FT-IR spectroscopy. , and were further structurally authenticated by X-ray crystallography. In the presence of [Ph3C][B(C6F5)4] and Al(i)Bu3, were highly active for cis-1,4-selective polymerization of isoprene, whereas /[Ph3C][B(C6F5)4]/Al(i)Bu3 promoted the polymerization in a living fashion. PMID- 26674735 TI - Single nucleotide polymorphisms of the SLC22A2 gene within the Xhosa population of South Africa. AB - Human organic cation transporter 2 (hOCT2) is thought to play a critical role in the uptake, pharmacological effects and/or adverse effects of many cationic clinical therapeutics and xenobiotics. Moreover, genetic variations in hOCT2 gene, SLC22A2, are increasingly being recognized as a possible mechanism that can explain individual variation in drug response. To screen for variations in this gene, SLC22A2 was directly sequenced in 96 healthy Xhosa individuals. A total of 27 variations, including three novel ones, were identified in SLC22A2: eight in exons, 15 in introns, and four in the 5'-untranslated region. The minor allele frequencies (MAF) of genetic variants observed in the Xhosa population were compared both to other African and other world populations. Seventeen of the variants observed in the SLC22A2 gene of the Xhosa population were specific to/or occurred at a higher frequency in African populations or populations with a recent connection to the African continent. PMID- 26674736 TI - Adverse drug reactions and organ damage: The skin. AB - Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. PMID- 26674737 TI - Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey. AB - AIMS: Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. METHODS AND RESULTS: A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. CONCLUSIONS: The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks. PMID- 26674734 TI - High density lipoproteins: Measurement techniques and potential biomarkers of cardiovascular risk. AB - Plasma high density lipoprotein cholesterol (HDL) comprises a heterogeneous family of lipoprotein species, differing in surface charge, size and lipid and protein compositions. While HDL cholesterol (C) mass is a strong, graded and coherent biomarker of cardiovascular risk, genetic and clinical trial data suggest that the simple measurement of HDL-C may not be causal in preventing atherosclerosis nor reflect HDL functionality. Indeed, the measurement of HDL-C may be a biomarker of cardiovascular health. To assess the issue of HDL function as a potential therapeutic target, robust and simple analytical methods are required. The complex pleiotropic effects of HDL make the development of a single measurement challenging. Development of laboratory assays that accurately HDL function must be developed validated and brought to high-throughput for clinical purposes. This review discusses the limitations of current laboratory technologies for methods that separate and quantify HDL and potential application to predict CVD, with an emphasis on emergent approaches as potential biomarkers in clinical practice. PMID- 26674738 TI - Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma. AB - BACKGROUND: KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features. METHODS: Total RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients. RESULTS: The two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6% (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4% (135/143) HCC samples and the mean H score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p=0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival. CONCLUSION: In this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients. PMID- 26674739 TI - Methods for flexible sample-size design in clinical trials: Likelihood, weighted, dual test, and promising zone approaches. AB - Sample size plays a crucial role in clinical trials. Flexible sample-size designs, as part of the more general category of adaptive designs that utilize interim data, have been a popular topic in recent years. In this paper, we give a comparative review of four related methods for such a design. The likelihood method uses the likelihood ratio test with an adjusted critical value. The weighted method adjusts the test statistic with given weights rather than the critical value. The dual test method requires both the likelihood ratio statistic and the weighted statistic to be greater than the unadjusted critical value. The promising zone approach uses the likelihood ratio statistic with the unadjusted value and other constraints. All four methods preserve the type-I error rate. In this paper we explore their properties and compare their relationships and merits. We show that the sample size rules for the dual test are in conflict with the rules of the promising zone approach. We delineate what is necessary to specify in the study protocol to ensure the validity of the statistical procedure and what can be kept implicit in the protocol so that more flexibility can be attained for confirmatory phase III trials in meeting regulatory requirements. We also prove that under mild conditions, the likelihood ratio test still preserves the type-I error rate when the actual sample size is larger than the re calculated one. PMID- 26674740 TI - Development and validation of an indirect competitive ELISA for quantification of recombinant staphylokinase in rabbit plasma: Application to pharmacokinetic study. AB - The relatively short circulatory half-life (2-3 min) of staphylokinase is a major drawback in the development of SAK- (staphylokinase) based thrombolytic drug. A rapid and sensitive method, based on indirect competitive ELISA, was developed and validated for quantitative determination of SAK in rabbit plasma. The dynamic range of the assay varied between 0.41 +/- 0.16 MUg/L and 9.03 +/- 0.38 MUg/L (R(2) = 0.98) for SAK in rabbit plasma. There were no dilution linearity issues apparent with this assay. The precision (% CV) ranged from 4.6-9.7% for the intraassay and from 17.1-19.3% for interassay. This validated method was successfully employed for evaluation of various pharmacokinetic parameters of SAK in rabbit. PMID- 26674741 TI - TALEN-mediated homologous recombination in Daphnia magna. AB - Transcription Activator-Like Effector Nucleases (TALENs) offer versatile tools to engineer endogenous genomic loci in various organisms. We established a homologous recombination (HR)-based knock-in using TALEN in the crustacean Daphnia magna, a model for ecological and toxicological genomics. We constructed TALENs and designed the 67 bp donor insert targeting a point deletion in the eyeless mutant that shows eye deformities. Co-injection of the TALEN mRNA with donor DNA into eggs led to the precise integration of the donor insert in the germ line, which recovered eye deformities in offspring. The frequency of HR events in the germ line was 2% by using both plasmid and single strand oligo DNA with 1.5 kb and 80 nt homology to the target. Deficiency of ligase 4 involved in non-homologous end joining repair did not increase the HR efficiency. Our data represent efficient HR-based knock-in by TALENs in D. magna, which is a promising tool to understand Daphnia gene functions. PMID- 26674742 TI - Irisin - a myokine potentially bridging muscle and fat tissue in cachexia. PMID- 26674744 TI - Regulatory exclusivities for medicinal products for human use in the EU. PMID- 26674743 TI - Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor. AB - Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People's Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. PMID- 26674745 TI - Standardized data collection to build prediction models in oncology: a prototype for rectal cancer. AB - The advances in diagnostic and treatment technology are responsible for a remarkable transformation in the internal medicine concept with the establishment of a new idea of personalized medicine. Inter- and intra-patient tumor heterogeneity and the clinical outcome and/or treatment's toxicity's complexity, justify the effort to develop predictive models from decision support systems. However, the number of evaluated variables coming from multiple disciplines: oncology, computer science, bioinformatics, statistics, genomics, imaging, among others could be very large thus making traditional statistical analysis difficult to exploit. Automated data-mining processes and machine learning approaches can be a solution to organize the massive amount of data, trying to unravel important interaction. The purpose of this paper is to describe the strategy to collect and analyze data properly for decision support and introduce the concept of an 'umbrella protocol' within the framework of 'rapid learning healthcare'. PMID- 26674746 TI - A comparison of the relative biological effectiveness of low energy electronic brachytherapy sources in breast tissue: a Monte Carlo study. AB - Electronic brachytherapy sources use low energy photons to treat the tumor bed during or after breast-conserving surgery. The relative biological effectiveness of two electronic brachytherapy sources was explored to determine if spectral differences due to source design influenced radiation quality and if radiation quality decreased with distance in the breast. The RBE was calculated through the number of DNA double strand breaks (RBEDSB) using the Monte Carlo damage simulator (MCDS) in combination with other Monte Carlo electron/photon spectrum calculations. 50kVp photons from the Intrabeam (Carl Zeiss Surgical) and Axxent (Xoft) through 40-mm spherical applicators were simulated to account for applicator and tissue attenuation in a variety of breast tissue compositions. 40kVp Axxent photons were also simulated. Secondary electrons (known to be responsible for most DNA damage) spectra at different distance were inputted into MCDS to calculate the RBEDSB. All RBEDSB used a cobalt-60 reference. RBEDSB data was combined with corresponding average photon spectrum energy for the Axxent and applied to model-based average photon energy distributions to produce an RBEDSB map of an accelerated partial breast irradiation (APBI) patient. Both Axxent and Intrabeam 50kVp spectra were shown to have a comparable RBEDSB of between 1.4 and 1.6 at all distances in spite of progressive beam hardening. The Axxent 40kVp also demonstrated a similar RBEDSB at distances. Most RBEDSB variability was dependent on the tissue type as was seen in rib (RBEDSB ~ 1.4), gland (~1.55), adipose (~1.59), skin (~1.52) and lung (~1.50). RBEDSB variability between both sources was within 2%. A correlation was shown between RBEDSB and average photon energy and used to produce an RBEDSB map of a dose distribution in an APBI patient dataset. Radiation quality is very similar between electronic brachytherapy sources studied. No significant reductions in RBEDSB were observed with increasing distance from the source. PMID- 26674747 TI - Trends in Sickle Cell Disease-related Priapism in U.S. Children's Hospitals. AB - OBJECTIVE: To define rates of priapism diagnosis and inpatient admission among males with sickle cell disease (SCD). PATIENTS AND METHODS: We retrospectively reviewed the Pediatric Health Information System database for males aged <21 years treated 2004-2012. We identified patients with SCD and priapism based on the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Logistic regression and generalized estimating equation models were used to control for confounding and to adjust for within hospital clustering of similar patients. RESULTS: We identified 17,186 males who were admitted 137,710 times during the study period. Of these, 362 (2.1%) were diagnosed with priapism on 748 admissions. There was a significant decrease in the number of priapism admissions among patients with SCD over time (0.81% in 2004 to 0.44% in 2012, P < .001). The number of patients diagnosed with SCD related priapism varied over time without a statistically significant trend (2.3% in 2004, 2.69% in 2008, 1.01% in 2012, P = .34). Rates of priapism admissions (0-4.4%) varied widely between hospitals. Older patient age was associated with an increased likelihood of a priapism admission in the multivariate logistic regression model after adjusting for treatment year, hospital region, and for hospital-level clustering of similar patients. CONCLUSION: From 2004 to 2012, the number of admissions for SCD-related priapism declined whereas the number of individual patients diagnosed with SCD-related priapism did not. Rates of priapism-related admissions in males with SCD vary widely among PHIS hospitals. PMID- 26674748 TI - Urothelial Cancer in Renal Transplant Recipients: Incidence, Risk Factors, and Oncological Outcome. AB - OBJECTIVE: To evaluate the incidence and risk factors for urothelial cancer (UC) as well as the oncological outcome and allograft function in renal transplant recipients. SUBJECTS/PATIENTS: We conducted a retrospective analysis of 1855 consecutive patients undergoing renal transplantation (TX) between February 1982 and May 2014 at a single center. UC incidence, overall and cancer-specific survival, recurrence and progression rates, risk factors for UC, and renal function were determined. Fisher's exact test and log-rank Mantel-Cox test were used as appropriate. RESULTS: In renal transplant recipients, incidence of de novo UC was 1.35% (25/1855). Deceased donor transplantation (P = .002), increased age at transplantation (P = .011), and analgesic abuse (P = .005) were significant risk factors for the development of UC post-TX. Progression rate and recurrence rate were doubled for post-TX-UC but stable for patients with pre-TX UC compared with the general population. Analgesic abuse was associated with worse cancer specific and overall survival in post-TX patients. The overall survival status was significantly lower for post-TX patients at a median of 34 months vs 222 months in control patients. Adjuvant treatment was scarcely used. UC had no significant influence on graft function. CONCLUSION: A higher incidence of UC was identified in renal transplant recipients compared with that for the general population. These observations justify screening for UC in renal transplant patients, especially considering that in a large proportion, a tentative diagnosis was possible with noninvasive urine analysis. Prudent adjuvant treatment for UC should be used. Limitations of this study were the retrospective design and the single-center experience. PMID- 26674749 TI - Evaluation of the Initial Treatment of Ureteroceles. AB - OBJECTIVE: To assess the results of the initial therapeutic approach to ureteroceles at our institution and the need for further interventions. PATIENTS AND METHODS: This is a retrospective study of all pediatric cases of ureterocele diagnosed at our center between January 2000 and December 2011. RESULTS: Forty three patients were analyzed. Initial diagnoses were ureterohydronephrosis in 34 (33 prenatal), febrile urinary tract infection in 5, and prolapsed ureterocele in 3. Expectant management was decided upon in 6 patients (14%). Of these, 1 required surgery. The remaining 37 (86%) initially underwent surgery: transurethral puncture (18), heminephrectomy (14), nephrectomy (3), and reimplantation (2). Twelve (66.6%) of the 18 patients who underwent primary puncture progressed well and required no further intervention. New-onset vesicoureteral reflux to the upper pole appeared after puncture in 3 patients, but none required treatment. Only 6 patients (33.3%) underwent a second procedure. Mean follow-up was 8.5 years (standard deviation: 3.08). CONCLUSION: Early endoscopic puncture is useful for decompression and often the definitive treatment. Although new-onset vesicoureteral reflux into the punctured system is the most common complication, it often resolves spontaneously. Early heminephrectomy in patients with nonfunctioning upper moieties yields excellent results but may not be necessary. Some patients may not need transurethral puncture or any surgical intervention at all. PMID- 26674750 TI - Short Stimulus, Long Response: Sodium and Calcium Dynamics Explain Persistent Neuronal Firing. PMID- 26674751 TI - A motor learning approach to training wheelchair propulsion biomechanics for new manual wheelchair users: A pilot study. AB - CONTEXT/OBJECTIVE: Developing an evidence-based approach to teaching wheelchair skills and proper propulsion for everyday wheelchair users with a spinal cord injury (SCI) is important to their rehabilitation. The purpose of this project was to pilot test manual wheelchair training based on motor learning and repetition-based approaches for new manual wheelchair users with an SCI. DESIGN: A repeated measures within-subject design was used with participants acting as their own controls. METHODS: Six persons with an SCI requiring the use of a manual wheelchair participated in wheelchair training. The training included nine 90-minute sessions. The primary focus was on wheelchair propulsion biomechanics with a secondary focus on wheelchair skills. OUTCOME MEASURES: During Pretest 1, Pretest 2, and Posttest, wheelchair propulsion biomechanics were measured using the Wheelchair Propulsion Test and a Video Motion Capture system. During Pretest 2 and Posttest, propulsion forces using the WheelMill System and wheelchair skills using the Wheelchair Skills Test were measured. RESULTS: Significant changes in area of the push loop, hand-to-axle relationship, and slope of push forces were found. Changes in propulsion patterns were identified post-training. No significant differences were found in peak and average push forces and wheelchair skills pre- and post-training. CONCLUSIONS: This project identified trends in change related to a repetition-based motor learning approach for propelling a manual wheelchair. The changes found were related to the propulsion patterns used by participants. Despite some challenges associated with implementing interventions for new manual wheelchair users, such as recruitment, the results of this study show that repetition-based training can improve biomechanics and propulsion patterns for new manual wheelchair users. PMID- 26674752 TI - Helium stability and its interaction with H in alpha-Al2O3: a first-principles study. AB - Little is known about hydrogen interaction with helium, an extrinsic defect, present in alpha-Al2O3 TPBs due to tritium decay and (n, a) reaction. Using density functional theory (DFT), the stability, structure and diffusion of He related complexes at the different positions (VAl(3-), V, Oi(2-) and octahedral interstitial sites (OISs)) in alpha-Al2O3, as well as the interactions with H, are determined under H2-rich conditions. A He atom favors occupation of Al vacancies, the centers of OISs or forms a dumbbell around Al vacancies, forming Hei, HeAl(3-), Hei-HeAl(3-), [V-Hei](0) and [Oi(2-)-He](2-) complexes, among of which HeAl(3-) forms most readily. VAl(3-) can attract He to form small stable He HeAl(3-) clusters, whereas only a He atom is trapped by an OIS, V and Oi(2-). Hei is more likely to diffuse into VAl(3-) and V than diffuse along the c-axis from one OIS to another. Hi(+) trapping into HeAl(3-) and [V-Hei](0) is thermodynamically and kinetically feasible, whereas dissociation of [Hei-H(+)](+) is more feasible. Forms of H-He complex defects in alpha-Al2O3 are Hei, Hi(+), [Hei-H(+)](+), [HeAl(3-)-H(+)](2-) and [HO(+)-Hei](+). HeAl(3-) and [V-Hei](0) present will increase the activation energy of H migration in alpha-Al2O3, which is favored for low H transport of TPBs. PMID- 26674753 TI - Prediction of Ocular Drug Distribution from Systemic Blood Circulation. AB - Systemically circulating drugs may distribute to ocular tissues across the blood ocular barriers. Ocular distribution is utilized in the treatment of ocular diseases with systemic medications, but ocular delivery of systemic drugs and xenobiotics may also lead to adverse ocular effects. Ocular distribution after systemic drug administration has not been predicted or modeled. In this study, distribution clearance between vitreous and plasma was obtained from a previous QSPR model for clearance of intravitreal drugs. These values were used in a pharmacokinetic simulation model to describe entry of unbound drug from plasma to vitreous. The simulation models predicted ocular distribution of 10 systemic drugs in rabbit eyes within 1.96 mean fold error and the distribution of cefepime from plasma to vitreous in humans. This is the first attempt to predict ocular distribution of systemic drugs. Reliable predictions were obtained using systemic concentrations of unbound drug, computational value of ocular distribution clearance, and a simple pharmacokinetic model. This approach can be used in drug discovery to estimate ocular drug exposure at an early stage. PMID- 26674754 TI - Chronic Pancreatitis and Pancreatic Cancer. AB - BACKGROUND: Pancreatic cancer (PC) is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Chronic pancreatitis (CP) is a common chronic inflammatory disease of unknown etiology that affects the pancreas. Epidemiological studies have identified CP to be a major risk factor for PC. SUMMARY: A greater understanding of the molecular mechanisms linking CP and PC has identified several common pathways that provide targets for future interventions. This article reviews those components in the CP-PC connection, including the role of macrophages, the maintenance of genome stability, cytokines, and other nodal factors such as nuclear factor kappa B, COX-2 and reactive oxygen species. KEY MESSAGE: The molecular mechanisms that underlie CP and PC provide novel targets for future therapies for PC. PRACTICAL IMPLICATIONS: The stromal-desmoplastic reaction plays an important role in initiating and sustaining chronic inflammation and tumor progression. Recently, two targeted anti-tumor agents, erlotinib and nab-paclitaxel, have shown promising therapeutic efficacy. Notably, both these agents target components (EGFR and SPARC) within the inflammatory stroma surrounding malignant cells, underscoring the importance of inflammation in pancreatic carcinogenesis. Identifying the common pathways linking CP and PC may help uncover additional novel targets for future therapies. PMID- 26674755 TI - Superoxide-hydrogen peroxide imbalance interferes with colorectal cancer cells viability, proliferation and oxaliplatin response. AB - The role of superoxide dismutase manganese dependent enzyme (SOD2) in colorectal cancer is presently insufficiently understood. Some studies suggest that high SOD2 levels found in cancer tissues are associated with cancer progression. However, thus far, the role of colorectal cancer superoxide-hydrogen peroxide imbalance has not yet been studied. Thus, in order to address this gap in extant literature, we performed an in vitro analysis using HT-29 colorectal cell line exposed to paraquat, which generates high superoxide levels, and porphyrin, a SOD2 mimic molecule. The effect of these drugs on colorectal cancer cell response to oxaliplatin was evaluated. At 0.1 MUM concentration, both drugs exhibited cytotoxic and antiproliferative effect on colorectal cancer cells. However, this effect was more pronounced in cells exposed to paraquat. Paraquat also augmented the oxaliplatin cytotoxic and antiproliferative effects by increasing the number of apoptosis events, thus causing the cell cycle arrest in the S and M/G2 phases. The treatments were also able to differentially modulate genes related to apoptosis, cell proliferation and antioxidant enzyme system. However, the effects were highly variable and the results obtained were inconclusive. Nonetheless, our findings support the hypothesis that imbalance caused by increased hydrogen peroxide levels could be beneficial to cancer cell biology. Therefore, the use of therapeutic strategies to decrease hydrogen peroxide levels mainly during oxaliplatin chemotherapy could be clinically important to the outcomes of colorectal cancer treatment. PMID- 26674756 TI - Microalbuminuria in subjects with hypertension attending specialist blood pressure clinics. AB - Albuminuria is associated with increased risk of cardiovascular disease and target organ damage in patients with diabetes mellitus. In nondiabetic hypertensive patients, the threshold at which microalbuminuria (MAU) increases risk is unclear and there is evidence that cardiovascular risk may be increased in individuals with MAU levels lower than the usual recommended screening thresholds. We compared two definitions of MAU (on the basis of three early morning urine samples) in a cohort of hypertensive patients attending two specialist clinics in Scotland: conventional (MAU(C)) albumin-to-creatinine ratio (ACR) >2.5-25 mg mmol(-1) in males or >3.5-25 mg mmol(-1) in females; and low grade (MAU(L)) ACR 1.2-2.5 in males or 1.7-3.5 mg mmol(-1) in females. Of the 1059 subjects screened, 786 (74%) were nondiabetic, with estimated glomerular filtration rate ?30 ml min(-1) per 1.73 m(2) and without gross proteinuria (low risk subset). The average age was 58+/-15 years, body mass index 30+/-6 kg m(-2) and 46% were males. The prevalence of MAU(C) was 11% and 9.5% in the overall and low-risk subset, respectively, whereas MAU(L) prevalence was 11.1% and 10% respectively. The prevalence of cardiovascular disease was higher (24%) with albuminuria (both MAU(C) and MAU(L)) compared with 14% among those without albuminuria. The use of MAU(L) doubled the number of hypertensive subjects with increased cardiovascular risk who can be targeted for more rigorous risk reduction strategies. Consideration should be given to reducing the current threshold for MAU. PMID- 26674757 TI - Incidence, aetiology and mortality secondary to hypertensive emergencies in a large-scale referral centre in Israel (1991-2010). AB - Hypertensive emergency (HE) is a life-threatening condition that requires immediate blood pressure (BP) reduction. Although it has been on the decline, the incidence of HE has recently increased in a few countries. The aim of the present retrospective study was to evaluate the incidence, aetiology and 1-year mortality of HE in a large medical centre over a 20-year period (1991-2010). The electronic medical records of all patient files who were hospitalized in the Chaim Sheba Medical Center in Israel from 1991 to 2010 with a primary diagnosis (at admission or discharge) of Malignant Hypertension, Hypertensive Emergency or Accelerated Hypertension were retrieved and analysed. The study interval was divided into four periods of 5 years each. Among 306 files reviewed, only 142 patients had a true HE. Average age at presentation was 63.3+/-16.5 years. Men were younger than women (59+/-16 vs 68+/-16 years; P<0.001). At presentation, most patients (80.3%) had been diagnosed with essential hypertension previously and were undertreated. Average maximum mean arterial pressure (MAP) was higher in men (169+/-22 mm Hg) than in women (161+/-17 mm Hg; P=0.026). The rate of HE decreased over the course of the study, from 12.7/100 000 admissions during 1991-1995 to 6.2/100 000 admissions (2006-2010). Similarly, 1-year mortality decreased from 16.7 to 3.6%. The rate of HE has decreased and the prognosis has improved over the last two decades. Appropriate BP control of patients with essential hypertension may further decrease the risk of HE. PMID- 26674758 TI - Pulse blood pressure and cardiovascular mortality in a population-based cohort of elderly Costa Ricans. AB - We studied the relationships between blood pressure (BP), pulse pressure (PP) and cardiovascular (CV) death in older adults using data from 2346 participants enrolled in the Costa Rican CRELES study, mean age 76 years (s.d. 10.2), 31% qualified as wide PP. All covariates included and analyzed were collected prospectively as part of a 4-year home-based follow-up; mortality was tracked for an additional 3 years, identifying 266 CV deaths. Longitudinal data revealed little change over time in systolic BP (SBP), a decline in diastolic BP, and widening of PP. Wide PP was associated with higher risk of CV death but only among individuals receiving antihypertensive drug therapy. Individuals with both wide PP and receiving therapy had 2.6 hazard rate of CV death relative to people with normal-PP plus not taking treatment (TRT), even adjusting for SBP. Increasing PP between visits was significantly associated to higher CV death independently of TRT status. SBP and DBP were not significantly associated to CV death when the effect of PP was controlled for. CONCLUSION: elderly hypertensive patients with wide or increasing PP, especially if receiving TRT, are the highest CV risk group, thus must be carefully assessed, monitored and treated with caution. PMID- 26674760 TI - Transphyseal Injury of Distal Humerus: A Commonly Missed Diagnosis in Neonates. AB - Distal humeral physeal injury is a rare entity in newborns. Lack of ossific nuclei of the distal humerus in neonates results in a diagnostic dilemma as the injury is radiologically not visible and is often mistaken as elbow dislocation. Ultrasonography and Magnetic resonance imaging help to clinch diagnosis in the early period where plain radiographs fail to detect this entity. This condition warrants high index of suspicion along with good clinical acumen for early diagnosis and immediate management with closed reduction and immobilization to avoid long term complications. We present a case of delayed diagnosis of distal humeral physeal separation in a neonate which was managed conservatively at our neonatal intensive care unit with a good outcome without functional deformity. PMID- 26674759 TI - Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis. AB - Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was <130 mm Hg before randomization for interventional studies or at baseline for prospective cohort studies. We identified nine eligible studies (486 patients): five randomized placebo-controlled trials; three randomized active drug-controlled trials; and one single-arm observational study. The mean differences in office SBP and diastolic BP (DBP) between the MRA and placebo groups were -9.4 (95% confidence interval (CI) -12.9 to -5.9) and -3.8 (95% CI, -5.5 to -2.2) mm Hg, respectively. Subgroup analysis results for study type, age, baseline office SBP and follow-up duration were similar to those of the main analysis. MRA mildly increased serum potassium (0.4 mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia. PMID- 26674761 TI - Plasma Concentrations of Trimethylamine-N-oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population. AB - BACKGROUND: Trimethylamine-N-oxide (TMAO) is a metabolite of carnitine, choline, and phosphatidylcholine, which is inversely associated with survival of cardiovascular disease (CVD) patients. OBJECTIVE: We examined the associations of diet with plasma concentrations of TMAO, choline, and betaine and the associations of TMAO with plasma concentrations of various cytokines. METHODS: Plasma TMAO, choline, and betaine concentrations were measured using LC-high resolution mass spectrometry in 271 participants, >=18 y old, of the Second Bavarian Food Consumption Survey, conducted in 2002 and 2003. Food consumption was assessed using at least two 24-h dietary recalls. Cytokines were measured in plasma with enzyme-linked immunosorbent assays. Geometric mean concentrations of TMAO, choline, and betaine by categories of meat, dairy food, egg, and fish consumption were computed, adjusted for sex, age, and BMI. Multivariable-adjusted geometric mean concentrations of cytokines [tumor necrosis factor-alpha (TNF alpha), soluble TNF receptors (sTNF-R) p55, sTNF-R p75, interleukin-6 (IL-6), and C-reactive protein (CRP)] were computed by quartiles of TMAO concentration using general linear models. RESULTS: Meat, egg, or fish consumption was not associated with TMAO, choline, or betaine concentrations (all P-trend >= 0.05). With increases in milk and other dairy food consumption, the plasma TMAO concentration increased [geometric mean bottom quartile of milk consumption: 2.08 MUM (95% CI: 1.69, 2.57 MUM); compared with top quartile: 3.13 MUM (95% CI: 2.56, 3.84 MUM); P trend = 0.008]. Participants in the top TMAO quartile had higher plasma concentrations of TNF-alpha, sTNF-R p55, and sTNF-R p75 than participants in the bottom quartile (percentage difference ranging between 14.4% and 17.3%; all P trend < 0.05), but there were no differences in plasma concentrations of CRP and IL-6 (all P-trend >= 0.05). CONCLUSIONS: Results of this study conducted among healthy adults from the general population do not indicate a strong effect of diet on plasma concentrations of TMAO, choline, or betaine, with the exception of a positive association between dairy food consumption and plasma TMAO concentrations. Also, plasma TMAO concentrations were positively associated with inflammation. Whether habitual diet is strongly linked to the plasma TMAO concentration, a potential marker of CVD risk, needs to be determined in further studies. PMID- 26674762 TI - High-Protein Exposure during Gestation or Lactation or after Weaning Has a Period Specific Signature on Rat Pup Weight, Adiposity, Food Intake, and Glucose Homeostasis up to 6 Weeks of Age. AB - BACKGROUND: Early-life nutrition has a programming effect on later metabolic health; however, the impact of exposure to a high-protein (HP) diet is still being investigated. OBJECTIVE: This study evaluated the consequences on pup phenotype of an HP diet during gestation and lactation and after weaning. METHODS: Wistar rat dams were separated into 2 groups fed an HP (55% protein) or normal protein (NP) (control; 20% protein) isocaloric diet during gestation, and each group subsequently was separated into 2 subgroups that were fed an HP or NP diet during lactation. After weaning, male and female pups from each mother subgroup were separated into 2 groups that were fed either an NP or HP diet until they were 6 wk old. Measurements included weight, food intake, body composition, blood glucose, insulin, glucagon, leptin, insulin-like growth factor I, and lipids. RESULTS: Feeding mothers the HP diet during gestation or lactation induced lower postweaning pup weight (gestation diet * time, P < 0.0001; lactation diet * time, P < 0.0001). Regardless of dams' diets, pups receiving HP compared with NP diet after weaning had 7% lower weight (NP, 135.0 +/- 2.6 g; HP, 124.4 +/- 2.5 g; P < 0.0001), 16% lower total energy intake (NP, 777 +/- 14 kcal; HP, 649 +/- 13 kcal; P < 0.0001) and 31% lower adiposity (P < 0.0001). Pups receiving HP compared with NP diet after weaning had increased blood glucose, insulin, and glucagon when food deprived (P < 0.0001 for all). The HP compared with the NP diet during gestation induced higher blood glucose in food-deprived rats (NP, 83.2 +/- 2.1 mg/dL; HP, 91.2 +/- 2.1 mg/dL; P = 0.046) and increased plasma insulin in fed pups receiving the postweaning NP diet (gestation diet * postweaning diet, P = 0.02). CONCLUSION: Increasing the protein concentration of the rat dams' diet during gestation, and to a lesser extent during lactation, and of the pups' diet after weaning influenced pup phenotype, including body weight, fat accumulation, food intake, and glucose tolerance at 6 wk of age. PMID- 26674764 TI - Zinc Absorption by Adults Is Similar from Intrinsically Labeled Zinc-Biofortified Rice and from Rice Fortified with Labeled Zinc Sulfate. AB - BACKGROUND: Biofortification of staple food crops is a promising strategy to combat zinc deficiency, and it is of particular interest for rice and crops that are not consumed as flours and therefore not suitable for postharvest fortification. Because zinc absorption is decreased by phytic acid (PA) and perhaps other dietary components, it is important to measure the absorption of zinc from a biofortified crop before determining its efficacy. OBJECTIVE: In this study, we compared the zinc absorption from zinc-biofortified rice (hydroponically enriched with (70)Zn) with that from a control rice of the same variety fortified with (70)ZnSO4 at point of use to reach the same total zinc content of 1.1 mg/meal. Both rice meals had a PA:Zn molar ratio of 12. METHODS: Fractional absorption of zinc (FAZ) was measured with the use of the double isotope tracer ratio method in 16 apparently healthy adults [18-45 y old; BMI (in kg/m(2)) 19-25] who consumed 2 single meals at 4-wk intervals in random order in a crossover design. RESULTS: The FAZ from the biofortified rice (mean +/- SD: 25.1 +/- 8.7%) did not differ significantly from that of the point-of-use fortified rice (mean +/- SD: 20.8 +/- 7.1%) (P = 0.08). CONCLUSIONS: These results suggest that the native zinc accumulated in the biofortified rice was readily released from the rice matrix and that its absorption by adults was influenced by PA and other food components in a similar way to the inorganic zinc compound added to the rice at point of use. Moreover, rice biofortification is likely to be as good as postharvest zinc fortification as an intervention strategy to combat zinc deficiency. This trial was registered at clinicaltrials.gov as NCT01633450. PMID- 26674763 TI - Absorption and Distribution Kinetics of the 13C-Labeled Tomato Carotenoid Phytoene in Healthy Adults. AB - BACKGROUND: Phytoene is a tomato carotenoid that may contribute to the apparent health benefits of tomato consumption. Although phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lycopene, suggesting the kinetics of phytoene and lycopene differ. OBJECTIVE: The objective of this study was to characterize the kinetic parameters of phytoene absorption, distribution, and excretion in adults, to better understand why biodistribution of phytoene differs from lycopene. METHODS: Four adults (2 males, 2 females) maintained a controlled phytoene diet (1-5 mg/d) for 42 d. On day 14, each consumed 3.2 mg (13)C-phytoene, produced using tomato cell suspension culture technology. Blood samples were collected at 0, 1-15, 17, 21, and 24 h and 2, 3, 4, 7, 10, 14, 17, 21, and 28 d after (13)C-phytoene consumption. Plasma unlabeled and plasma-labeled phytoene concentrations were determined using ultra HPLC-quadrupole time-of-flight-mass spectrometry, and data were fit to a 7 compartment carotenoid kinetic model using WinSAAM 3.0.7 software. RESULTS: Subjects were compliant with a controlled phytoene diet, consuming a mean +/- SE of 2.5 +/- 0.6 mg/d, resulting in a plasma unlabeled phytoene concentration of 71 +/- 14 nmol/L. A maximal plasma (13)C-phytoene concentration of 55.6 +/- 5.9 nM was achieved 19.8 +/- 9.2 h after consumption, and the plasma half-life was 2.3 +/- 0.2 d. Compared with previous results for lycopene, phytoene bioavailability was nearly double at 58% +/- 19%, the clearance rate from chylomicrons was slower, and the rates of deposition into and utilization by the slow turnover tissue compartment were nearly 3 times greater. CONCLUSIONS: Although only differing from lycopene by 4 double bonds, phytoene exhibits markedly different kinetic characteristics in human plasma, providing insight into metabolic processes contributing to phytoene enrichment in plasma and tissues compared with lycopene. This trial was registered at clinicaltrials.gov as NCT01692340. PMID- 26674765 TI - Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats. AB - BACKGROUND: In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value. OBJECTIVE: The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model. METHODS: In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats. RESULTS: Fecal Bifidobacterium concentrations (mean log copy number +/- SEM) were higher (P = 0.003) in BF (8.17 +/- 0.3) and SPCF-fed infants (8.29 +/- 0.3) compared with those fed the SFs (6.94 +/- 0.3). Fecal acetic acid (mean +/- SEM) was also higher (P = 0.007) in the BF (5.5 +/- 0.2 mg/g) and SPCF (5.3 +/- 2.4 mg/g) groups compared with SF-fed babies (4.3 +/- 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 +/- 2.6 mg/g) than in those fed SPCF (30.6 +/- 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF. CONCLUSIONS: Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiao tong University School of Medicine as XHEC-C-2012-024. PMID- 26674767 TI - Ultrasound and echocardiographic findings obtained in the second and third trimesters of gestation in fetuses with normal karyotype and increased nuchal translucency. PMID- 26674766 TI - Recent Advances in Tumor Ablation for Hepatocellular Carcinoma. AB - Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID- 26674768 TI - Morphological and Molecular Characterization of Phasmarhabditis huizhouensis sp. nov. (Nematoda: Rhabditidae), a New Rhabditid Nematode from South China. AB - The genus Phasmarhabditis is an economically important group of rhabditid nematodes, to which the well-known slug-parasite P. hermaphrodita belongs. Despite the commercial use of Phasmarhabditis species as an attractive and promising approach for pest control, the taxonomy and systematics of this group of rhabditids are poorly understood, largely because of the lack of diagnostic morphological features and DNA sequences for distinguishing species or inferring phylogenetic relationship. During a nematode sampling effort for identifying free living relatives of Caenorhabditis elegans in Huizhou City, Guangdong, China, a novel species belonging to the genus Phasmarhabditis was isolated from rotting leaves. Detailed morphology of the gonochoristic P. huizhouensis sp. nov. was described and illustrated. The adult female has a robust body, a relatively short and wide buccal capsule conjoined by a rhabditiform pharynx. Females are characterized by a short cupola-shaped tail end bearing a slender pointed tip, with the junction flanked by a pair of 'rod-like' phasmids. Males have an open peloderan bursa that is supported by 9 pairs of genital papillae and 1 terminal pair of phasmids. P. huizhouensis sp. nov. is morphologically very similar to the type species Phasmarhabditis papillosa but is distinguishable by its male caudal traits. The new species is readily differentiated from other taxa in the genus by its female tail shape. Molecular phylogenetic inferences based on small subunit (SSU) and the D2-D3 domain of large subunit (LSU) ribosomal DNA genes reveal that P. huizhouensis sp. nov. forms a unique branch in both phylogenies which is genetically related to P. hermaphrodita and other parasites such as Angiostoma spp. The host associations of P. huizhouensis sp. nov. and its ability to parasitize slugs are unknown. PMID- 26674769 TI - Reconsidering Health Consequences of the Chernobyl Accident. AB - The Chernobyl accident led to major human suffering caused by the evacuation and other counter-measures. However, the direct health consequences of the accident related radiation exposures, besides the acute effects and small number of thyroid cancers, have not been observed. This absence is challenged by some influential groups affecting public policies who claim that the true extent of radiogenic health consequences is covered up. We consider such claims. The most conservative (in this case - overestimating) linear no-threshold hypothesis was used to calculate excess cancer expectations for cleanup workers, the population of the contaminated areas and the global population. Statistical estimations were performed to verify whether such expected excess was detectable. The calculated cancer excess for each group is much less than uncertainties in number of cancer cases in epidemiological studies. Therefore the absence of detected radiation carcinogenesis is in full correspondence with the most conservative a priori expectations. Regarding the cover-up claims, rational choice analysis was performed. Such analysis shows that these claims are ill-founded. The present overcautious attitude to radiological hazards should be corrected in order to mitigate the present suffering and to avoid such suffering in the future. PMID- 26674770 TI - Podocalyxin as a Prognostic Marker in Gastric Cancer. AB - BACKGROUND: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein associated with aggressive tumor phenotype and poor prognosis in several forms of cancer. The aim of this study was to investigate PODXL expression in gastric cancer by use of two different antibodies. METHODS: By tumor-tissue microarrays and immunohistochemistry we evaluated PODXL expression in tumor specimens from 337 patients who underwent surgery for gastric adenocarcinoma at Helsinki University Hospital. We used two different antibodies: HPA2110, which is a polyclonal antibody and an in-house monoclonal antibody called HES9, to investigate the association of PODXL expression with clinicopathologic variables and patient survival. RESULTS: PODXL staining was positive by the polyclonal antibody in 153 (57.5%) cases and by the monoclonal antibody in 212 (76%). Polyclonal antibody expression was associated with intestinal cancer type (p<0.001). Monoclonal antibody staining was associated with age over 66 (p = 0.001), with intestinal cancer (p<0.001), and with small tumor size (<= 5 cm; p = 0.024). Both antibodies were associated with high S-phase fraction (p = 0.022; p = 0.010), and high tumor proliferation index (Ki-67; p = 0.003; p = 0.001). PODXL positivity by the polyclonal antibody indicated reduced gastric-cancer-specific 5-year survival of 24.0% (95% CI 16.9-31.1), compared to 43.3% (95% CI 33.7-52.9) for patients with PODXL negativity (p = 0.001). The result remained significant in multivariable analysis (HR = 3.17; 95% CI 1.37-7.34, p = 0.007). CONCLUSION: In gastric cancer, PODXL expression by the polyclonal antibody HPA2110 is an independent marker of poor prognosis. PMID- 26674773 TI - Bacillus piscicola sp. nov., isolated from Thai fish sauce (Nam-pla). AB - A Gram-reaction-positive, spore-forming, rod-shaped bacterium, designated NR1-3 2T, was isolated from fish sauce collected from a factory in Chonburi province, Thailand. Strain NR1-3-2T grew at pH 5-10 (optimum 7.5), at 21-48 degrees C (optimum 37 degrees C) and with 0-15 % (w/v) NaCl (optimum 1-3 %). The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. Menaquinone with seven isoprene units (MK-7) was the major isoprenoid quinone. The strain contained anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0 as major cellular fatty acids. Diphosphatidylglycerol, phosphatidyl glycerol and one unknown glycolipid were detected as major polar lipids. On the basis of 16S rRNA gene sequence analysis, strain NR1-3-2T belonged to the genus Bacillus and was closely related to Bacillus iranensis DSM 23995T (97.4 % similarity). Strain NR1 3-2T exhibited low DNA-DNA relatedness (31.2-39.8 %) with B. iranensis DSM 23995T. The DNA G+C content was 44.2 mol%. On the basis of phenotypic characteristics, DNA-DNA relatedness and phylogenetic analyses, the strain is considered to represent a novel species of the genus Bacillus and the name Bacillus piscicola sp. nov. is proposed. The type strain is NR1-3-2T ( = JCM 19598T = LMG 28281T = PCU 340T = TISTR 2295T). PMID- 26674772 TI - Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population. AB - Multiple risk variants of schizophrenia have been identified by Genome-wide association studies (GWAS). As a complement for GWAS, previous pathway-based analysis has indicated that cell adhesion molecules (CAMs) pathway might be involved in the pathogenesis of schizophrenia. However, less replication studies have been reported. Our objective was to investigate the association between CAMs pathway and schizophrenia in the Chinese Han population. We first performed a pathway analysis utilizing our previous GWAS data. The CAMs pathway (hsa04514) was significantly associated with schizophrenia using hybrid gene set-based test (P = 1.03*10-10) and hypergeometric test (P = 5.04*10-6). Moreover, 12 genes (HLA A, HLA-C, HLA-DOB, HLA-DPB1, HLA-DQA2, HLA-DRB1, MPZ, CD276, NLGN1, NRCAM, CLDN1 and ICAM3) were modestly significantly associated with schizophrenia (P<0.01). Then, we selected one promising gene neuroligin 1 (NLGN1) to further investigate the association between eight significant SNPs and schizophrenia in an independent sample (1814 schizophrenia cases and 1487 healthy controls). Our study showed that seven SNPs of NLGN1 and two haplotype blocks were significantly associated with schizophrenia. This association was confirmed by the results of combined analysis. Among them, SNP rs9835385 had the most significant association with schizophrenia (P = 2.83*10-7). Furthermore, in silico analysis we demonstrated that NLGN1 is preferentially expressed in human brain and SNP rs1488547 was related to the expression level. We validated the association of CAMs pathway with schizophrenia in pathway-level and identified one susceptibility gene NLGN1. Further investigation of the roles of CAMs pathway in the pathogenesis of schizophrenia is warranted. PMID- 26674771 TI - The microbiome of the built environment and mental health. AB - The microbiome of the built environment (MoBE) is a relatively new area of study. While some knowledge has been gained regarding impacts of the MoBE on the human microbiome and disease vulnerability, there is little knowledge of the impacts of the MoBE on mental health. Depending on the specific microbial species involved, the transfer of microorganisms from the built environment to occupant's cutaneous or mucosal membranes has the potential to increase or disrupt immunoregulation and/or exaggerate or suppress inflammation. Preclinical evidence highlighting the influence of the microbiota on systemic inflammation supports the assertion that microorganisms, including those originating from the built environment, have the potential to either increase or decrease the risk of inflammation-induced psychiatric conditions and their symptom severity. With advanced understanding of both the ecology of the built environment, and its influence on the human microbiome, it may be possible to develop bioinformed strategies for management of the built environment to promote mental health. Here we present a brief summary of microbiome research in both areas and highlight two interdependencies including the following: (1) effects of the MoBE on the human microbiome and (2) potential opportunities for manipulation of the MoBE in order to improve mental health. In addition, we propose future research directions including strategies for assessment of changes in the microbiome of common areas of built environments shared by multiple human occupants, and associated cohort-level changes in the mental health of those who spend time in the buildings. Overall, our understanding of the fields of both the MoBE and influence of host-associated microorganisms on mental health are advancing at a rapid pace and, if linked, could offer considerable benefit to health and wellness. PMID- 26674775 TI - Will transoesophageal echocardiography become a standard tool for anesthetists to assess haemodynamic status during non-cardiac surgeries? Case report and literature review. AB - A 53-year-old male, with no history of cardiovascular diseases, underwent elective extended right hemihepatectomy for large metastatic tumor. Approximately 2 hours after the start of procedure sudden onset of severe hypotension associated with profound desaturation and significant fall in end-tidal carbon dioxide pressure was noted. Transoesophageal echocardiography was performed and massive air embolism was confirmed. Patient was turned into Trendelenburg position, inspired oxygen was increased to 100% and positive end-expiratiory pressure turned up to 10 cm H20. Patient was further resuscitated with iv fluids, blood products and vasopressors under surveillance of transoesophageal echocardiography. In this report we present a case in which intraoperative use of transoesophageal echocardiography by trained anaesthetist helped to immediately identify the cause of sudden hypotension and hypoxaemia. Transoesophageal echocardiographywas also a valuable tool for direct monitoring of efficacy of instituted treatment. PMID- 26674776 TI - Phase IIb clinical trial of ranibizumab for the treatment of uveitic and idiopathic choroidal neovascular membranes. AB - AIM: To assess the efficacy of intravitreal ranibizumab for the treatment of new onset inflammatory choroidal neovascularisation (iCNV), including both uveitic and idiopathic CNVs. METHODS: Single-centre, open-label, non-randomised Phase IIb clinical trial. Patients fulfilling strict entry criteria of new onset iCNV were given monthly intravitreal ranibizumab injections for 3 months. Thereafter, re treatment was based on evidence of persisting activity. All patients completed trial follow-up. Optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) were performed at every visit. Fluorescein angiography was performed at baseline, months 4 and 12. Descriptive analysis and Wilcoxon non parametric test were performed for analysis. RESULTS: 15 patients, 10 women with a mean age of 48.8 years (range 24-85 years) were included in the study. The mean number of injections was 4.33 (range 3-7). There was a statistically significant difference in the BCVA at month 4 (p=0.001) and at month 12 (p=0.001) compared with baseline. The mean gain in BCVA at month 4 compared with baseline was 20+/ 15.36 letters (mean+/-SD), and at month 12 was 21+/-16.97 letters. There was a statistically significant difference in the mean central subfield thickness (CST) at baseline versus month 4 (p=0.003) and month 12 (p=0.001). CONCLUSION: Patients gained vision (mean of 21 letters at 12 months) and showed reduced CST. These results support the continued use of ranibizumab in the treatment of iCNV. TRIAL REGISTRATION NUMBER: 2008-007476-19, results. PMID- 26674774 TI - Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK. AB - The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host's cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-DeltaN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that process. PMID- 26674777 TI - Evaluation and comparison of the new swept source OCT-based IOLMaster 700 with the IOLMaster 500. AB - PURPOSE: To compare the measurements and failure rates obtained with a new swept source optical coherence tomography (OCT)-based biometry to IOLMaster 500. SETTING: Eye Clinic, Baskent University Faculty of Medicine, Ankara, Turkey. DESIGN: Observational cross-sectional study and evaluation of a new diagnostic technology. METHODS: 188 eyes of 101 subjects were included in the study. Measurements of axial length (AL), anterior chamber depth (ACD), corneal power (K1 and K2) and the measurement failure rate with the new Zeiss IOLMaster 700 were compared with those obtained with the IOLMaster 500. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired samples t test, and their correlation was evaluated by intraclass correlation coefficient (ICC). RESULTS: The mean age was 68.32+/-12.71 years and the male/female ratio was 29/72. The agreements between two devices were outstanding regarding AL (ICC=1.0), ACD (ICC=0.920), K1 (ICC=0.992) and K2 (ICC=0.989) values. IOLMaster 700 was able to measure ACD AL, K1 and K2 in all eyes within high-quality SD limits of the manufacturer. IOLMaster 500 was able to measure ACD in 175 eyes, whereas measurements were not possible in the remaining 13 eyes. AL measurements were not possible for 17 eyes with IOLMaster 500. Nine of these eyes had posterior subcapsular cataracts and eight had dense nuclear cataracts. CONCLUSIONS: Although the agreement between the two devices was excellent, the IOLMaster 700 was more effective in obtaining biometric measurements in eyes with posterior subcapsular and dense nuclear cataracts. PMID- 26674778 TI - Microcatheter-assisted trabeculotomy versus rigid probe trabeculotomy in childhood glaucoma. AB - PURPOSE: To compare microcatheter-assisted trabeculotomy with standard rigid probe trabeculotomy for the treatment of childhood glaucoma. METHODS: The early postoperative (12 months) results of microcatheter-assisted trabeculotomy (group 1) performed by single surgeon were retrospectively compared with those of rigid probe trabeculotomy (group 2) performed by the same surgeon in patients treated for childhood glaucoma. Success was defined as an intraocular pressure (IOP) <21 mm Hg with at least a 30% reduction from preoperative IOP with (qualified success) or without (complete success) the use of anti-glaucoma medication. RESULTS: A total of 43 eyes of 36 patients were included. Mean IOP in group 1 was significantly lower than that in group 2 at 6 months (17.0+/-5.1 vs 22.5+/-9.8; p=0.042), 9 months (16.3+/-5.0 vs 21.6+/-9.6; p=0.009) and 12 months (14.8+/-2.5 vs 19.0+/-7.1; p=0.049) postoperatively. The mean percentage reduction in IOP from preoperative to the last postoperative follow-up was greater in group 1 (47.3+/-17.7%) than in group 2 (34.2+/-21.9%) (p=0.036). group 1 demonstrated an 81.0% complete and 86.4% qualified success rate, exceeding the 51.6% complete (p=0.060) and 61.9% qualified (p=0.037) success rate of group 2. There were no long-term complications in either group, but choroidal detachment occurred in one eye in group 2. CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is a more effective treatment and is as safe as traditional trabeculotomy with a rigid probe for primary congenital glaucoma in the early postoperative course. TRIAL REGISTRATION NUMBER: ChiCTR-OCC-15005789, Results. PMID- 26674779 TI - Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up. AB - AIMS: To compare the outcomes of Ex-PRESS versus trabeculectomy at 3 years. METHODS: Consenting patients aged 18-85 years with medically uncontrolled open angle glaucoma scheduled for trabeculectomy were included in this study. 63 subjects were randomised to undergo Ex-PRESS (32) or trabeculectomy (31). Follow up data included intraocular pressure (IOP), glaucoma medications, visual acuity (VA), complications and additional interventions. Complete success was defined as IOP between 5 and 18 mm Hg and 20% reduction from baseline without glaucoma medications, while qualified success was with or without glaucoma medications. RESULTS: Complete success at 2 and 3 years was 43% vs 42% (p=0.78) and 35% vs 38% (p=0.92) in Ex-PRESS versus trabeculectomy, respectively. Qualified success at 2 and 3 years was 59% vs 76% (p=0.20) and 52% vs 61% (p=0.43) in Ex-PRESS versus trabeculectomy, respectively. Mean IOP at 2 and 3 years was 12.5+/-5.1 mm Hg vs 10.3+/-3.7 mm Hg (p=0.07) and 13.3+/-4.5 mm Hg vs 11.1+/-4.4 mm Hg (p=0.10) for Ex-PRESS versus trabeculectomy, respectively. At 3 years, 47.6% of Ex-PRESS and 50% of trabeculectomy patients were on glaucoma medications (p=1.00). No difference in VA was found after 3 years (logarithm of minimum angle of resolution 0.43+/-0.4 vs 0.72+/-0.8 for Ex-PRESS vs trabeculectomy, p=0.11). When excluding patients who underwent reoperation VA was better in the Ex-PRESS group at 1, 2 and 3 years. There were no complications after the first year in either group. CONCLUSIONS: We found no difference in success rates, mean IOP or other secondary outcomes between Ex-PRESS and trabeculectomy after 3 years of follow up. TRIAL REGISTRATION NUMBER: NCT01263561; post results. PMID- 26674780 TI - Incidence and factors associated with complications of sutured and sutureless cataract surgery following pars plana vitrectomy at a tertiary referral centre in Turkey. AB - AIMS: To evaluate the incidence of and factors contributing to intraoperative and postoperative complications of eyes with previous pars plana vitrectomy (PPV) undergoing phacoemulsification and intraocular lens (IOL) implantation for cataract. METHODS: The intraoperative and postoperative complications and observations in 513 eyes of 485 patients with previous PPV undergoing sutured and sutureless cataract surgery were assessed. Associations between preoperative characteristics and complications during and after the surgery were explored. RESULTS: The median interval from PPV to cataract surgery was 15.7+/-19.5 months. The mean follow-up period was 35.1+/-31.4 months. Intraoperative complications and observations were: posterior capsular plaque in 50 eyes (9.7%), posterior capsule rupture in 28 eyes (5.5%), loss of nuclear material into vitreous in 17 eyes (3.3%), and zonular dialysis in 12 eyes (2.3%). The most common postoperative complication was posterior capsular opacification (PCO) in 171 eyes (33.3%). PCO correlated with duration of PPV (p<0.001), younger age (p=0.003), and shorter interval from PPV to cataract surgery (p=0.01). Higher rates of postoperative IOL decentration and dislocation correlated with male sex, 20-gauge PPV, 20-gauge PPV with scleral buckling surgery (p<0.001), and longer interval from PPV to silicone oil extraction (p=0.006). Endophthalmitis was not observed in either the sutured or sutureless groups of patients. CONCLUSIONS: Longer duration of PPV surgery, a longer interval from PPV to silicone oil extraction, prior 20-gauge PPV, and 20-gauge PPV with scleral buckling surgery seem to influence the safety and outcomes of cataract surgery. Sutureless phacoemulsification in vitrectomised eyes was not associated with a higher incidence of endophthalmitis, suprachoroidal effusion or haemorrhage. PMID- 26674782 TI - Prelemniscal Radiations: A New Reliable Landmark of the Thalamic Nucleus Ventralis Intermedius Location. AB - BACKGROUND: The thalamic nucleus ventralis intermedius (Vim nucleus) is the main surgical target for the management of intractable tremor. The Vim nucleus cannot be reliably located with routine stereotactic imaging, and so targeting relies on indirect coordinates. OBJECTIVE: We propose to investigate if colored fractional anisotropy (FA) mapping can help to locate the Vim nucleus by identifying its borders, particularly the prelemniscal radiations (Raprl) that lie below and behind the nucleus. METHOD: We retrospectively reviewed the colored FA maps for 18 consecutive patients having undergone gamma knife stereotactic Vim thalamotomy for disabling tremor. RESULTS: The Raprl were easily located on colored FA maps and enabled the identification of the lower and posterior borders of the Vim nucleus in all patients. In the medial plane, the mean distance +/- SD between the Raprl and Vim nucleus was 0.77 +/- 1.19 mm (range: 0.1-3.3). The Raprl were located 1.35 +/- 1.33 mm (range: 0.2-3.9) behind the Vim nucleus and 1.99 +/- 1.23 mm (range: 0.7-4.4) below it. The mean vector distance +/- SD between the Vim nucleus and the Raprl was 3 +/- 1.38 mm (range: 1.25-5.2). CONCLUSION: The Raprl can be easily seen on colored FA maps and constitute a reliable landmark for the borders of the Vim nucleus. PMID- 26674781 TI - The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis. AB - Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 MUg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 MUg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis. PMID- 26674783 TI - China's human resources for maternal and child health: a national sampling survey. AB - BACKGROUND: In order to achieve the Millennium Development Goals (MDG) 4 and 5, the Chinese Government has invested greatly in improving maternal and child health (MCH) with impressive results. However, one of the most important barriers for further improvement is the uneven distribution of MCH human resources. There is little information about the distribution, quantity and capacity of the Chinese MCH human resources and we sought to investigate this. METHODS: Cities at prefectural level were selected by random cluster sampling. All medical and health institutions providing MCH-related services in the sampled areas were investigated using a structured questionnaire. The data were weighted based on the proportion of the sampled districts/cities. Amount, proportions and numbers per 10,000 population of MCH human resources were estimated in order to reveal the quantity of the Chinese MCH human resources. The capacity of MCH human resources was evaluated by analyzing data on the education level and professional skills of the staff. RESULTS: There were 77,248 MCH workers in China in 2010. In general, 67.6% and 71.9% of the women's and children's health care professionals had an associate degree or higher, whereas around 30% had only high-school or lower degrees. More than 40% of the women's health workers were capable of providing skilled birth attendance, but these proportions varied between different institutions and locations. CONCLUSIONS: Evidence from this study highlights that Chinese MCH human resources are not in shortage in the national level. However, the quantity and capacity of MCH human resources are not evenly distributed among different institutions and locations. Finally there is a need in the improvement of the MCH services by improving the quality of MCH human resources. PMID- 26674785 TI - Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents. AB - Melanoma is a leading cause of mortality from skin cancer and has a poor prognosis. Despite rapid advances in the treatment of this tumor type, the efficacy of current chemo-/targeted-therapies is still limited owing to the lack of sufficient drug accumulation in the tumor tissue and development of chemo resistance. Recently, the application of mesenchymal stem cells (MSCs) in cancer therapy has gained substantial attention, suggesting their potential roles as an intriguing vehicle in improving the delivery of targeted agents. MSCs are genetically modified with suicide tumor suppressor genes to inhibit cell signaling pathways associated with the progression and metastatic features of melanoma. Here we describe the clinical application of MSCs in melanoma with a particular emphasis on recent findings on the role of MSC expressing a distinct set of biologically functional chemokines and tumor suppressing agents. Accumulating data has shown the tumor- oriented homing capacity of MSCs and their applications as a vehicle (e.g., adipose derived mesenchymal stem cells expressing TRAIL, interferon-alpha/gamma, pigment epithelium-derived factor and cytosine deaminase). Several questions regarding possible potential and intrinsic mechanisms that might induce tumorigenesis and drug resistance are yet to be addressed for tailoring MSC-nbased treatment of melanoma. PMID- 26674784 TI - Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population. AB - BACKGROUND: Methylation is a common epigenetic modification which may play a crucial role in cancer development. To investigate the association between methylation of COX-2 in blood leukocyte DNA and risk of gastric cancer (GC), a nested case-control study was conducted in Linqu County, Shandong Province, a high risk area of GC in China. METHODS: Association between blood leukocyte DNA methylation of COX-2 and risk of GC was investigated in 133 GCs and 285 superficial gastritis (SG)/ chronic atrophic gastritis (CAG). The temporal trend of COX-2 methylation level during GC development was further explored in 74 pre GC and 95 post-GC samples (including 31 cases with both pre- and post-GC samples). In addition, the association of DNA methylation and risk of progression to GC was evaluated in 74 pre-GC samples and their relevant intestinal metaplasia (IM)/dysplasia (DYS) controls. Methylation level was determined by quantitative methylation-specific PCR (QMSP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis. RESULTS: The medians of COX-2 methylation levels were 2.3% and 2.2% in GC cases and controls, respectively. No significant association was found between COX-2 methylation and risk of GC (OR, 1.15; 95% CI: 0.70-1.88). However, the temporal trend analysis showed that COX-2 methylation levels were elevated at 1-4 years ahead of clinical GC diagnosis compared with the year of GC diagnosis (3.0% vs. 2.2%, p=0.01). Further validation in 31 GCs with both pre- and post-GC samples indicated that COX-2 methylation levels were significantly decreased at the year of GC diagnosis compared with pre-GC samples (1.5% vs. 2.5%, p=0.02). No significant association between COX-2 methylation and risk of progression to GC was found in subjects with IM (OR, 0.50; 95% CI: 0.18-1.42) or DYS (OR, 0.70; 95% CI: 0.23-2.18). Additionally, we found that elder people had increased risk of COX-2 hypermethylation (OR, 1.55; 95% CI: 1.02-2.36) and subjects who ever infected with H. pylori had decreased risk of COX-2 hypermethylation (OR, 0.54; 95% CI: 0.34-0.88). CONCLUSIONS: COX-2 methylation exists in blood leukocyte DNA but at a low level. COX-2 methylation levels in blood leukocyte DNA may change during GC development. PMID- 26674786 TI - Mnesic Profiles According to the Size of Pericerebral Hematoma in Patients with Traumatic Brain Injury. AB - OBJECTIVE: The study aims to assess mnesic performances of patients, following a head injury with pericerebral hematoma, according to the size of the hematoma. METHODS: Cognitive performances of a group of 25 patients with large (>=10 mm) pericerebral hematomas were compared with those of a matched group of 25 patients with small (<10 mm) ones and a matched group of patient with moderate-severe traumatic brain injury with no pericerebral hematoma. RESULTS: Executive function and information processing speed were not significantly different. Mnesic performances of the large hematomas group were more impaired: cuing effect (63.5 vs. 80% and 83%; p = 0.002; x03B7;2 = 0.183) and total recall (37.5/48 vs. 43.2 and 44.2; p = 0.022; x03B7;2 = 0.65) of the Free and Cued Recall Test. CONCLUSION: Memory of those in the large hematomas group was impaired with probable storage/consolidation disorders. To identify specific cognitive disorders resulting from large hematomas, it is justified to systematically screen these disorders and to adapt their management. PMID- 26674787 TI - B-Cell Disorders and Curcumin. AB - Clinical studies with patients with early hematological malignancies (ie, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or stage 0/1 chronic lymphocytic leukemia) suggest that early intervention with curcumin, derived from the spice turmeric, may lead to prolonged survival and delay in progressive disease in some of these patients. PMID- 26674788 TI - [High-risk non-disabling ischemic cerebrovascular events: a window of opportunity for stroke control]. PMID- 26674789 TI - [Attending and strengthening the use of non-invasive positive pressure therapy for motor neuron disease]. PMID- 26674790 TI - [Ventilation function disorder of flail arm syndrome]. AB - OBJECTIVE: To study the features of ventilation function in patients with flail arm syndrome (FAS). METHODS: The clinical data of 351 patients with sporadic amyotrophic lateral sclerosis (ALS) from 2009 to 2013 were retrospectively reviewed. Among them, 329 were classical ALS and 22 were FAS. The differences of forced vital capacity (FVC) between FAS and classical ALS were analyzed. RESULTS: The percent predicted FVC (FVC% pred) values were (88.0 +/- 9.5)% in FAS and (84.3 +/- 16.8)% in classical ALS including 4 and 128 patients with abnormal FVC% pred (< 80%) in FAS and classical ALS, respectively. The FVC% pred levels were significantly higher in FAS subjects [(88.0 +/- 9.5)%] than in classical ALS subjects of bulb [(80.0 +/- 14.8)%] or those of upper limb [(80.8 +/- 16.0)%] onset with duration over 12 months (All P < 0.05). The proportion of subjects with FVC% pred < 80% was statistically lower in FAS [18.2% (4/22)] than in both classical ALS of upper limb onset [42.8% (80/187); P = 0.037] and classical ALS with duration over one year [48.5% (48/99); P = 0.009]. CONCLUSIONS: Impaired ventilation function occurs less and later in FAS than that in classical ALS of upper limb onset with duration over one year, suggesting later and less requirement for non-invasive positive pressure ventilation treatment for FAS patients. Differentiation of FAS subjects from ALS helps assess prognosis and make treatment plan for these patients. PMID- 26674791 TI - [Clinical study of stroke in young adults with infective endocarditis]. AB - OBJECTIVE: To investigate the clinical features of stroke in young adults with infective endocarditis (IE). METHODS: This is a retrospective analysis of clinical data of young patients (aged between 18 and 44 years) diagnosed with IE in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2003 to March 2013. RESULTS: Three hundred IE patients (209 male and 91 female) were enrolled with mean age of (31.8 +/- 7.8) years old. Fourteen of them were prosthetic valve endocarditis. All of the cases were found vegetations. The vegetations were mainly distributed in the mitral valve and/or aortic valve (262/300 patients). Congenital heart disease and rheumatic valvular disease were most frequently background diseases. Thirty-five cases (11.7%) were complicated with stroke. Among them, 21 cases were with cerebral infarction (including 7 subjects with hemorrhagic transformation), 9 cases with cerebral hemorrhage, 3 cases with subarachnoid hemorrhage, and 2 with reasons unknown. Within the 21 cerebral infarction cases, the infarction sites were mainly distributed in internal carotid artery system with 5 cases involving bilateral internal carotid artery systems and 2 vertebro-basilar artery systems. As to the cerebral hemorrhage, lobar were the bleeding sites in all cases, and mainly distributed in internal carotid artery system. The proportions of left-sided endocarditis and rheumatic valvular disease were significantly higher in patients with stroke than those without [100.0% (35/35) vs 86.4% (229/265), P = 0.02; 22.8% (8/35) vs 6.4% (17/265), P = 0.001, respectively]. Regression analysis showed that the OR of the rheumatic valvular disease for stroke in young IE patients was 4.950 (95% CI 1.626-15.072), and the OR of stroke for death was 8.387 (95% CI 1.997-35.225), respectively. CONCLUSIONS: Stroke is common in young patients with IE. Cerebral infarction often involves multiple vascular systems, and is prone to hemorrhagic transformation. Intracerebral hemorrhage often occurs in lobar. Rheumatic valvular disease might be a risk factor for stroke in young patients with IE, which is an independent risk factor for death of these patients. PMID- 26674792 TI - [Clinicopathological study of non-Langerhans cell histiocytosis in central nervous system]. AB - OBJECTIVE: To explore the clinicopathological features and imaging characteristics of non-Langerhans cell histiocytosis in central nerve system, thus to facilitate the diagnosis and differential diagnosis. METHODS: A total of ten cases were enrolled in the study, with seven cases of Rosai-Dorfman disease (RDD) and three cases of xanthoma disseminatum (XD). Data on the clinicopathological features, imaging, immunophenotype and prognosis were collected and analyzed. RESULTS: Seven patients with RDD, 5 males and 2 females with the mean age of 46.7 years old, all presented as dural-based or intraparenchymal hypo- to isointense lesions on T1 and T2 with post-contrast enhancement. The polymorphous admixture of histiocytes, lymphocytes and plasma cells was observed in a fibrous stroma, with emperipolesis of some histiocytes. The immunohistostaining of CD11c, CD68, MAC387 and S-100 was positive in the histiocytes, while the staining of CD1alpha was negative. Five patients recovered after the operation, while one patient died of the disease. All the 3 XD patients were female, with the median age of 20.7 years old. All XD patients presented as multiple intraparenchymal hypointense lesions on T1 and hyperintense lesions on T2 with post-contrast enhancement. The infiltration of foam-like histiocytes, a few Touton giant cells, lymphocytes and eosnophils was observed in all XD patients. The immunohistostaining of CD68 and CD11c was positive in the histiocytes and that of MAC387 partly positive, while the staining of S-100 and CD1alpha was negative. One XD patient survived well, while another one died of the disease. CONCLUSIONS: The diagnosis of RDD and XD should be based on their typical morphology and immunophenotype and should be differentiated from Langerhans cell histiocytosis and other non-Langerhans cell histiocytosis. Non Langerhans cell histiocytosis in central nerve system often presents untypical clinical presentation and imaging features, thus the communication and cooperation between clinician and pathologist is needed. PMID- 26674793 TI - [A clinical analysis of 16 patients with maternal listeriosis]. AB - OBJECTIVE: To summarize the clinical characteristics and outcome of maternal listeriosis so as to improve the understanding of disease and the level of diagnosis and treatment. METHODS: Retrospectively, 16 cases of maternal listeriosis, who were treated at Peking Union Medical College Hospital between March 2007 and December 2014 were reviewed. Maternal listeriosis is defined when a pregnant woman presents with symptoms as listeriosis, meanwhile Listeria monocytogenes is isolated from sterile tissue or peripheral blood, or from a non sterile site (uterus swab) or pathological evidence of chorioamnionitis. The neonatal listeriosis is diagnosed as acute listeria sepsis. RESULTS: The mean age of these 16 patients was (30.0 +/- 3.9) years old. There were 1, 8, 7 patients with listeriosis diagnosed in the first, second and third trimester of pregnancy, respectively. All had an acute onset of illness (<= 2 weeks), the median time from onset to presentation was 2.5 days. Clinical manifestations included fever (93.8%, 15/16), leukocytosis (78.6%, 11/14), chorioamnionitis (77.8%, 7/9), gastrointestinal symptoms (37.5%, 6/16) and fetal movement decrease (31.3%, 5/16). Listeria monocytogenes were isolated from blood (6 cases), uterus swab (6 cases), blood plus uterus swab (1 case), and neonates (3 cases). All maternal cases recovered well after the termination of pregnancy, even none of them had received empiric antibiotics sensitive to listeria. A very high proportion of adverse pregnancy outcomes occurred (15/16, 93.8%). There were 8 fetal losses. Seven neonates were complicated with listeria sepsis and treated successfully. CONCLUSIONS: The patients with maternal listeriosis commonly presented with acute fever and an extremely high incidence of adverse pregnancy outcomes, however empiric antibiotics can hardly cover this pathogenic bacterium. So both pregnant women and clinicians should maintain a high level of vigilance against listeriosis and pay more attention to dietetic hygiene. PMID- 26674794 TI - [Association between serum leptin, adiponectin, visfatin, obesity and hypertension in female]. AB - OBJECTIVE: This study was aimed to investigate the relationship between serum leptin, adiponectin, visfatin levels and obesity and essential hypertension in female subjects. METHODS: According to BMI and blood pressure, 206 female participants enrolled were divided into four groups: group 1: obesity and hypertension (48 cases); group 2: non-obesity but hypertension (48 cases); group 3: obesity and normotension (56 cases) and group 4: normal BMI and blood pressure (54 cases). Serum leptin, adiponectin and visfatin levels were detected and their relationships to BMI, blood pressure and waist circumference were analysed. RESULTS: Serum leptin levels were significantly higher in non-obese groups [group 2: (4.47 +/- 1.26) ng/L, group 4: (3.73 +/- 1.18) ng/L] than in obese groups [group 1: (2.97 +/- 1.46) ng/L, group 3: (3.02 +/- 1.18) ng/L], and higher in hypertension groups than in normotension groups. Serum adiponectin levels were obviously higher in group 4 [38.99 (19.75, 103.71) ug/L] than in the other three groups. There were no significant differences in adiponectin levels among group 1, 2 and 3. Serum levels of visfatin were lower in normotension groups [group 3: 3.19 (0.96, 9.45) ng/L; group 4:3.23 (1.92, 4.64) ng/L] than in hypertension groups [group 1: 3.84 (3.40, 5.35) ng/L; group 2: 3.75(1.63, 6.67) ng/L] irrespective of obesity. Logistics regression analysis showed that there was 1.6%, 8.3%, or 5.45% increased risk for hypertension for each 1 ug/L decrease in adiponectin, 1 cm increase in waist circumference, or 1 ug/L increase in visfatin level in obesity, respectively. No relationship could be viewed between leptin and hypertension. CONCLUSIONS: Adiponectin and visfatin levels were correlated with obesity and blood pressure in females. Both adipokines may play a crucial role in the development of hypertension in female obesity. PMID- 26674795 TI - [The application of peripartum use of pulmonary artery catheter in pregnant patients with pulmonary hypertension]. AB - OBJECTIVE: To investigate the application and value of pulmonary artery catheterization (PAC) in pregnant patients with pulmonary hypertension (PH). METHODS: The clinical data of pregnant patients with PH who were treated between 2006 and 2014 in surgical intensive care unit (SICU) at Capital Medical University affiliated Beijing Anzhen Hospital were retrospectively analysed. The differences of the clinical characteristics and outcome between PAC inserted patients and PAC not inserted patients were compared. RESULTS: The systolic pulmonary artery pressure (sPAP) measured by preoperative echocardiography has no significant difference between the PAC inserted patients [(103.0 +/- 24.1) mmHg (1 mmHg = 0.133 kPa)] and PAC not inserted patients [(96.4 +/- 27.3) mmHg; P = 0.175]. SPAP may be overestimated or underestimated by echocardiography compared with PAC with a gap from -38.4 mmHg to 49.5 mmHg. The rates of idiopathic pulmonary arterial hypertension (20.0% vs 3.2%) and continuous use of epidural anesthesia (89.1% vs 65.1%) were higher in PAC inserted patients compared with PAC not inserted patients. Norepinephrine, dobutamine, sildenafil, alprostadil, iloprost and low molecular weight heparin were more widely used in PAC inserted patients. The mortality rate and the rates of low birth weight (63.9% vs 30.6%) and very low birth weight infants (19.4% vs 13.9%) were all higher in PAC inserted patients, while the rate of induced abortion was lower in this group (5.5% vs 17.5%). The length of stay in surgical intensive care unit [6.0 (5.0) d vs 1.0 (3.0) d], postoperative length of stay [8.0 (6.0) d vs 8.0 (4.0) d] and total hospital costs [43 999.22 (38 267.27) RMB vs 14 878.24 (10 564.47) RMB] were all higher in PAC inserted patients. The incidence rate of PAC related complications was 7.3%. CONCLUSIONS: In moderate or severe PH pregnant patients with severe clinical symptoms, perioperative insertion of PAC helps to monitor the perinatal pulmonary arterial pressure(PAP) and guide treatment, potentially improving clinical outcomes and lowering the short term mortality. PAC can't be replaced by echocardiography in measuring PAP. PMID- 26674796 TI - [A comparative study of different bedside lung ultrasound examination for the location and signs of diaphragmatic points]. AB - OBJECTIVE: To investigate the differences of the locations and signs of the phrenic points between the Modified Bedside Lung Ultrasound Examination (M-BLUE) and Bedside Lung Ultrasound Examination (BLUE). METHODS: A total of 61 consecutive patients who were treated in the Department of Critical Care Medicine at Peking Union Medical College Hospital in January and February of 2015 were enrolled in this study. BLUE and M-BLUE were both performed on each patient. The differences of examination results were compared. RESULTS: (1) There were 47.5% (58/122) different locations of the phrenic points and 18.0% (22/122) different echo-signs between the BLUE protocol and the M-BLUE protocol. (2) Compared with BLUE protocol, changes of locations [67.9% (19/28) vs 33.3% (11/33)] and signs [42.9% (12/28) vs 12.1% (4/33)] of the phrenic points in the M-BLUE protocol in patients with respiratory failure were significantly higher than those without pulmonary diseases. Among 5 patients with acute respiratory distress syndrome and 6 patients with chronic obstructive pulmonary disease, all presented changes in locations of the phrenic point in the M-BLUE protocol, while 3 and 4 showed changes in signs respectively. (3) Signs of the phrenic point in the M-BLUE protocol were more consistent with the result of the chest CT than those in the BLUE protocol. CONCLUSION: Compared with BLUE protocol, M-BLUE protocol seems more accurate in locating the phrenic point and more specific for the diagnosis of pulmonary disease. Compared with BLUE protocol, M-BLUE is more valuable for critical patients. PMID- 26674797 TI - [The relationship between anti-phospholipase A2 receptor antibody and idiopathic membranous nephropathy]. AB - OBJECTIVE: To explore the value of anti-phospholipase A2 receptor (PLA2R) antibody in the diagnosis and disease activity monitoring of idiopathic membranous nephropathy (IMN). METHODS: A total of 233 patients with IMN proven by kidney biopsy at Peking Union Medical College Hospital from January 2012 to March 2014 were enrolled in this study. Another 46 patients with non-IMN kidney diseases at the same period were selected as control group. Serum titer of anti PLA2R antibody was measured by quantitative enzyme-linked immuno sorbent assay (ELISA) at the time of renal biopsy. Clinical data were reviewed and retrospectively analyzed. The diagnostic accuracy of anti-PLA2R antibody in IMN was estimated by ROC curve. RESULTS: The total sensitivity of anti-PLA2R antibody was 60.0% in IMN. However, the sensitivity increased to 71.3% in patients who did not receive immuno-suppression therapies. The specificity of anti-PLA2R antibody was 100.0%, of which was not detected in any of the 25 control patients with lupus nephritis. The area under ROC curve of anti-PLA2R antibody for IMN diagnosis was 0.800. The prevalence of positive anti-PLA2R antibody in nephrotic range proteinuria group and non-nephrotic range proteinuria group were 68.3% and 41.7% (P < 0.05), respectively. The positive rates in patients with serum albumin level less than 30 g/L and more than 30 g/L were 67.3% and 44.6% (P < 0.05), respectively. Hypoalbuminemia became worse (P < 0.05) and the proportion of nephrotic arrange proteinuria rose significantly (P < 0.05) according to the elevation of antibody level. CONCLUSIONS: Anti-PLA2R antibody has high sensitivity and notable specificity for the diagnosis of IMN, which reveals good diagnostic accuracy. The antibody positive rate is affected by immunosuppression therapy, disease activity and other clinical status. Moreover, the antibody could reflect the disease activity. PMID- 26674798 TI - [An analysis of the questionnaire survey about the first year residency training in internal medicine in Peking Union Medical College Hospital]. AB - OBJECTIVE: To evaluate the effects of medical residency training program in postgraduate-year-one (PGY-1) residents at Peking Union Medical College (PUMC) Hospital. METHODS: PGY-1 medical residents at PUMC Hospital were surveyed by a self-administered questionnaire after they completed their first year residency. RESULTS: Forty-nine residents who completed their first year residency training participated in the survey with a 100% response rate. Before training, only a few had bedside (n = 18) and on-call experiences (n = 10). At the end of the one-year training, all the residents (100%) considered themselves being improved to certain degrees, especially in clinical practice capability, and passed all the examinations. However, 53.1% and 8.2% of all the residents agreed that they need to improve their abilities in teaching (n = 26) and doctor-patient communication (n = 4), respectively. All residents hoped to get further improved by taking part in various forms of teaching activities, including experience summary/sharing and basic skills training. During the first year, 95.9% of them participated in all teaching activities in medicine actively. CONCLUSIONS: The tradition and current models of medical residency training program at PUMC Hospital had a significant impact on professional development of the 1st year resident physicians. It is critical to focus on basic skill training and multi-level teaching to improve residents' clinical competency. PMID- 26674799 TI - Can Erectile Dysfunction in Young Patients Serve as a Surrogate Marker for Coronary Artery Disease? AB - INTRODUCTION: Early diagnosis and expeditious management of coronary artery disease (CAD) has a rewarding survival benefit. AIM: To study whether erectile dysfunction (ED) serves as a surrogate marker for CAD in a young patient. SETTINGS AND DESIGN: Males (n=207) between ages 20-60 years with ED were evaluated prospectively for risk factors for CAD. MATERIALS AND METHODS: Blood Glucose Levels (BGL) fasting and post meal), lipid profile (LP) and 12 lead electrocardiogram (ECG) was done in all of them. International Index of Erectile Function-5 (IEF-5) was used for the evaluation of ED. Those with abnormal parameters were assessed by cardiologists by echocardiography, stress test and if necessary coronary angiography (Non-Invasive or Invasive). STATISTICAL ANALYSIS: All the data were analysed using SPSS. 16 statistical software (SPSS Inc., Chicago, IL, USA). All data are expressed as mean and standard deviation. The Student's t-test was used to compare means between groups, and the chi-square test was used to compare proportions between the groups. P-value <0.05 was considered statistically significant. All confidence intervals (CIs) are two tailed and calculated at the 0.05 level. RESULTS: Out of 207, 149 patients had at least one abnormal screening parameter. All underwent cardiology consultation and 2D ECHO and Stress test. Thirty six patients underwent coronary angiography. CAD was found in 22 patients. Of these, 19 patients had severe ED. Nine patients were between 20-40 years of age (13.23%). All 9 young patients had deranged LP; severe ED. Six patients were smokers while nobody was hypertensive. CONCLUSION: ED serves as a surrogate marker for CAD in young patients (p=0.001). Presence of risk factors and lab abnormalities in young patients with ED warrants a cardiology referral to detect CAD. PMID- 26674801 TI - Food security top issue for Diabetes in Indigenous Peoples Stream. PMID- 26674800 TI - Addressing biological uncertainties in engineering gene circuits. AB - Synthetic biology has grown tremendously over the past fifteen years. It represents a new strategy to develop biological understanding and holds great promise for diverse practical applications. Engineering of a gene circuit typically involves computational design of the circuit, selection of circuit components, and test and optimization of circuit functions. A fundamental challenge in this process is the predictable control of circuit function due to multiple layers of biological uncertainties. These uncertainties can arise from different sources. We categorize these uncertainties into incomplete quantification of parts, interactions between heterologous components and the host, or stochastic dynamics of chemical reactions and outline potential design strategies to minimize or exploit them. PMID- 26674802 TI - Effect of Quorum Sensing by Staphylococcus epidermidis on the Attraction Response of Female Adult Yellow Fever Mosquitoes, Aedes aegypti aegypti (Linnaeus) (Diptera: Culicidae), to a Blood-Feeding Source. AB - Aedes aegypti, the principal vector of yellow fever and dengue fever, is responsible for more than 30,000 deaths annually. Compounds such as carbon dioxide, amino acids, fatty acids and other volatile organic compounds (VOCs) have been widely studied for their role in attracting Ae. aegypti to hosts. Many VOCs from humans are produced by associated skin microbiota. Staphyloccocus epidermidis, although not the most abundant bacteria according to surveys of relative 16S ribosomal RNA abundance, commonly occurs on human skin. Bacteria demonstrate population level decision-making through quorum sensing. Many quorum sensing molecules, such as indole, volatilize and become part of the host odor plum. To date, no one has directly demonstrated the link between quorum sensing (i.e., decision-making) by bacteria associated with a host as a factor regulating arthropod vector attraction. This study examined this specific question with regards to S. epidermidis and Ae. aegypti. Pairwise tests were conducted to examine the response of female Ae. aegypti to combinations of tryptic soy broth (TSB) and S. epidermidis wildtype and agr- strains. The agr gene expresses an accessory gene regulator for quorum sensing; therefore, removing this gene inhibits quorum sensing of the bacteria. Differential attractiveness of mosquitoes to the wildtype and agr- strains was observed. Both wildtype and the agr- strain of S. epidermidis with TSB were marginally more attractive to Ae. aegypti than the TSB alone. Most interestingly, the blood-feeder treated with wildtype S. epidermidis/TSB attracted 74% of Ae. aegypti compared to the agr- strain of S. epidermidis/TSB (P <= 0.0001). This study is the first to suggest a role for interkingdom communication between host symbiotic bacteria and mosquitoes. This may have implications for mosquito decision-making with regards to host detection, location and acceptance. We speculate that mosquitoes "eavesdrop" on the chemical discussions occurring between host-associated microbes to determine suitability for blood feeding. We believe these data suggest that manipulating quorum sensing by bacteria could serve as a novel approach for reducing mosquito attraction to hosts, or possibly enhancing the trapping of adults at favored oviposition sites. PMID- 26674803 TI - Vehicle Systems and Excipients Used in Minipig Drug Development Studies. AB - Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal nonclinical studies, in lieu of the dog or nonhuman primate, for compounds delivered via standard systemic routes of administration. Little is known about the tolerability of different excipients in minipigs; sharing knowledge of excipient tolerability and compositions previously used in nonclinical studies may avoid testing of inadequate formulations, thereby contributing to reduced animal usage. This article reviews vehicles employed in the Gottingen((r))minipig based on the combined experience from a number of pharmaceutical companies and contract research organizations. The review includes vehicles tolerated for single or multiple dosing by the Gottingen minipig, some of which are not appropriate for administration to other common nonrodent species (e.g., dogs). By presenting these data for dermal, oral, subcutaneous, and intravenous routes of administration, studies to qualify these vehicles in minipigs can be minimized or avoided. Additionally, investigators may more frequently consider using the minipig in place of higher species if the tolerability of a vehicle in the minipig is known. PMID- 26674804 TI - The Use of Minipig in Drug Discovery and Development: Pros and Cons of Minipig Selection and Strategies to Use as a Preferred Nonrodent Species. AB - The pig was introduced more than 20 years ago in drug development following attempts of finding a species that shares better homology with human than the dog, based on biophysiological parameters. However, miniaturization, standardized breeding, and health status control were required before the pig could find a broader than niche application in pharmaceutical industry. During the years of experience with minipigs in pharmaceutical research and the science evolving rapidly, the selection of a nonrodent animal species for preclinical safety testing became primarily driven by pharmacological (target expression homologous function), pharmacokinetic, and biophysiological considerations. This offered a broad field of application for the minipig, besides the well-established use in dermal projects in all areas of drug development but also in novel approaches including genetically modified animals. In this article, we look at recent approaches and requirements in the optimal selection of a nonrodent model in pharmaceutical development and critically ask how good a choice the minipig offers for the scientist, how did the testing environment evolve, and what are the key requirements for a broader use of the minipig compared to the other well established nonrodent species like dog or monkey. PMID- 26674806 TI - Determinants of venom-specific IgE antibody concentration during long-term wasp venom immunotherapy. AB - BACKGROUND: Venom immunotherapy (VIT) is an effective treatment for subjects with systemic allergic reactions (SR) to Hymenoptera stings, however there are few studies concerning the relevance of the venom specific IgE changes to decide about VIT cessation. We assessed IgE changes during a 5-year VIT, in patients stung and protected within the first 3 years (SP 0-3) or in the last 2 years (SP 3-5), and in patients not stung (NoS), to evaluate possible correlations between IgE changes and clinical protection. METHODS: Yellow jacket venom (YJV)-allergic patients who completed 5 years of VIT were retrospectively evaluated. Baseline IgE levels and after the 3rd and the 5th year of VIT were determined; all patients were asked about field stings and SRs. RESULTS: A total of 232 YJV allergic patients were included and divided into the following groups: 84 NoS, 72 SP 0-3 and 76 SP 3-5. IgE levels decreased during VIT compared to baseline values (chi(2) = 346.029, p < 0.001). Recent vespid stings accounted for significantly higher IgE levels despite clinical protection. IgE levels after 5 years of VIT correlated significantly with Mueller grade (F = 2.778, p = 0.012) and age (F = 6.672, p = 0.002). During follow-up from 1 to 10 years after VIT discontinuation, 35.2 % of the contacted patients reported at least one field sting without SR. CONCLUSIONS: The yellow jacket-VIT temporal stopping criterion of 5 years duration did not result in undetectable IgE levels, despite a long-lasting protection. A mean IgE decrease from 58 to 70 % was observed, and it was less marked in elderly patients or in subjects with higher Mueller grade SR. PMID- 26674807 TI - Synthesis of 2,3,5,6-tetrafluoro-pyridine derivatives from reaction of pentafluoropyridine with malononitrile, piperazine and tetrazole-5-thiol. AB - Some pentafluoropyridine derivatives have been synthesized by the reaction of pentafluoropyridine with appropriate C, S and N-nucleophile such as malononitrile, 1-methyl-tetrazole-5-thiol and piperazine. These reactions provided 4-substituted 2,3,5,6-tetrafluoropyridine derivatives in good yields. All the compounds were characterized using (1)H, (13)C and (19)F-NMR spectroscopy and X-ray crystallography. PMID- 26674805 TI - Identifying gene-gene interactions that are highly associated with Body Mass Index using Quantitative Multifactor Dimensionality Reduction (QMDR). AB - BACKGROUND: Despite heritability estimates of 40-70 % for obesity, less than 2 % of its variation is explained by Body Mass Index (BMI) associated loci that have been identified so far. Epistasis, or gene-gene interactions are a plausible source to explain portions of the missing heritability of BMI. METHODS: Using genotypic data from 18,686 individuals across five study cohorts - ARIC, CARDIA, FHS, CHS, MESA - we filtered SNPs (Single Nucleotide Polymorphisms) using two parallel approaches. SNPs were filtered either on the strength of their main effects of association with BMI, or on the number of knowledge sources supporting a specific SNP-SNP interaction in the context of BMI. Filtered SNPs were specifically analyzed for interactions that are highly associated with BMI using QMDR (Quantitative Multifactor Dimensionality Reduction). QMDR is a nonparametric, genetic model-free method that detects non-linear interactions associated with a quantitative trait. RESULTS: We identified seven novel, epistatic models with a Bonferroni corrected p-value of association < 0.1. Prior experimental evidence helps explain the plausible biological interactions highlighted within our results and their relationship with obesity. We identified interactions between genes involved in mitochondrial dysfunction (POLG2), cholesterol metabolism (SOAT2), lipid metabolism (CYP11B2), cell adhesion (EZR), cell proliferation (MAP2K5), and insulin resistance (IGF1R). Moreover, we found an 8.8 % increase in the variance in BMI explained by these seven SNP-SNP interactions, beyond what is explained by the main effects of an index FTO SNP and the SNPs within these interactions. We also replicated one of these interactions and 58 proxy SNP-SNP models representing it in an independent dataset from the eMERGE study. CONCLUSION: This study highlights a novel approach for discovering gene-gene interactions by combining methods such as QMDR with traditional statistics. PMID- 26674808 TI - Isolated axillary lymph node tuberculosis in ultrasonography. A case report. AB - We present a rare case of isolated axillary lymph node tuberculosis. A 66-year old patient was admitted in order to perform the diagnostics of a painless tumor of the left armpit. Blood biochemistry tests and chest X-ray did not show any abnormalities. In the ultrasound examination a solid structure of the dimensions of 1.8*1 cm of irregular outline with adjacent hypoechogenic lymph nodes was visualized. The diagnosis of tuberculosis was based on histopathologic examination of the excised tumor. In the latter years an increase in extrapulmonary type of tuberculosis has been observed. Extrapulmonary tuberculosis may appear in practically each organ, nevertheless it affects pleura most often. Lymph node tuberculosis is the second, when it comes to the prevalence rate, type of extrapulmonary tuberculosis. In the majority of cases of lymph node tuberculosis it affects superficial lymph nodes. In the ultrasound examination a packet of pathological, enlarged and hypoechogenic lymph nodes is stated. In 1/3 of cases the central part of the nodes is hyperechogenic which indicates its caseation necrosis. Lymph nodes have a tendency to be matted and they have blurred outline. We observed this type of lymph node image in the presented patient. This image may be a diagnostic hint. Nevertheless, in the differentiation diagnostics one should take many other disease entities into consideration, inter alia: sarcoidosis, lymphomas, fungal infections, neoplastic metastases; the latter ones have an image most similar to tuberculosis lymph nodes. Tuberculosis ought to be considered in differential diagnosis of atypical masses. PMID- 26674809 TI - Blood safety and zoonotic emerging pathogens: now it's the turn of Zika virus! PMID- 26674810 TI - Expression and function of purinergic receptors in platelets from apheresis derived platelet concentrates. AB - BACKGROUND: The storage of platelets affects platelet integrity and functionality, a process named platelet storage lesion (PSL). Reduced adenosine diphosphate (ADP)-induced platelet aggregation is a typical manifestation of PSL. However, the role of ADP receptors in this context has not been evaluated yet. The aim of this study was, therefore, to investigate surface expression and function of the purinergic receptors P2Y1, P2Y12 and P2X1 in stored platelet concentrates. MATERIAL AND METHODS: Platelets were obtained from venous whole blood and from apheresis-derived platelet concentrates stored for 0, 2 and 5 days. Purinergic receptor expression was measured by flow cytometry and western blot analysis. Receptor function was determined by calcium-induced fluorescence (P2Y1 and P2X1) or by flow cytometric measurement of the platelet reactivity index (P2Y12). RESULTS: The basal surface expression and total content of purinergic receptors remained unchanged throughout storage. After an initial reduction during apheresis, P2X1-mediated calcium flux was maintained, whereas the P2Y1-mediated increase of calcium flux gradually decreased during the course of storage. In contrast, the platelet reactivity index was comparable in freshly obtained and stored platelets. DISCUSSION: The function of the P2Y12 receptor is maintained during storage of apheresis-derived platelet concentrates. However, the impairment of P2X1 and especially of P2Y1 receptor function indicated by decreased receptor-mediated calcium flux is an important mechanism contributing to reduced ADP responsiveness of stored platelets. PMID- 26674811 TI - Convalescent plasma: new evidence for an old therapeutic tool? AB - Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20(th) century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme. PMID- 26674812 TI - Iron-deficiency anaemia in the Emergency Room: a new opportunity for the use of intravenous iron. PMID- 26674813 TI - Donating blood for research: a potential method for enhancing customer satisfaction of permanently deferred blood donors. AB - BACKGROUND: Each year, a large number of individuals in Australia are deferred from donating blood. A deferral may have a negative impact on donor satisfaction and subsequent word-of-mouth communication. The Australian Red Cross Blood Service (the Blood Service) is, therefore, investigating options for managing service interactions with deferred donors to maintain positive relationships. While public research institutes in Australia have established independent research donor registries, other countries provide programmes allowing deferred donors to donate blood for research via blood collection agencies. This study examined attitudes towards donating blood for research use in a sample of permanently deferred Australian donors. MATERIALS AND METHODS: Donors permanently deferred because of a risk of variant Creutzfeldt-Jakob disease (n=449) completed a postal survey that examined attitudes towards research donation. RESULTS: The majority of participants were interested in donating blood for research (96%), and joining a registry of research donors (93%). Participants preferred to donate for transfusion or clinical research, and were willing to travel large distances. Results indicated that positive attitudes towards the Blood Service would be extended if the opportunity to donate blood was provided. These findings indicate a desire for continued engagement with the Blood Service despite deferral. DISCUSSION: Donating blood for research is a potential way of maintaining positive relationships with permanently deferred donors which also benefits the health research community. Through maintaining positive relationships with deferred donors, positive word-of-mouth activity can be stimulated. Further work is needed to determine the feasibility of implementing research donation through the Blood Service in Australia. PMID- 26674814 TI - Differences in social representation of blood donation between donors and non donors: an empirical study. AB - BACKGROUND: Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. MATERIALS AND METHODS: Participants filled in the Adapted Self Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. RESULTS: The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. DISCUSSION: Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments. PMID- 26674815 TI - Zika virus and the never-ending story of emerging pathogens and transfusion medicine. AB - In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naive territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine. PMID- 26674816 TI - Beyond stopping the bleed: short-term episodic prophylaxis with recombinant activated factor FVII in haemophilia patients with inhibitors. AB - Preventing haemarthroses and arthropathy is a major challenge in patients with haemophilia and inhibitors, as treatment options are limited. One potential strategy is short-term episodic prophylaxis, which extends bypassing agent therapy beyond the resolution of bleeding to include the post-bleed inflammatory phase. At the 13th Zurich Haemophilia Forum, an expert panel reviewed the rationale behind this strategy, explored its current use with recombinant activated factor VII (rFVIIa) and considered treatment monitoring and optimisation. Two protocols are currently used for short-term episodic prophylaxis, both of which stipulate on-demand rFVIIa until resolution of bleeding, followed by daily dosing for >=3 days to prevent re-bleeds. Short-term episodic prophylaxis should be individualised to optimise outcomes, perhaps through early treatment initiation or by combining rFVIIa with other treatments (e.g. factor VIII, tranexamic acid). Encouraging treatment compliance can also improve outcomes. Additionally, there is a need to develop objective clinical outcome measures, biomarkers and imaging protocols that can monitor treatment outcomes and joint disease in patients with inhibitors. A proactive approach incorporating a systematic package of care is needed. Currently, short-term episodic prophylaxis with rFVIIa may be an alternative treatment option to on demand treatment for patients with inhibitors. PMID- 26674817 TI - On risk appraisal of behaviour. PMID- 26674818 TI - Severe skin radiodermatitis fully healed with the use of platelet gel and a hyperbaric chamber. PMID- 26674819 TI - A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia. AB - BACKGROUND: Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron deficiency anaemia in a fast-track anaemia clinic within the ED. MATERIALS AND METHODS: From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb>=12 g/dL and/or Hb increment >=2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. RESULTS: Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9+/-2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. DISCUSSION: Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID- 26674820 TI - Low-dose continuous infusion of factor VIII in patients with haemophilia A. AB - BACKGROUND: Patients with haemophilia A (HA) or B (HB) can be given prophylactic or on-demand treatment administered by continuous infusion or bolus injections of factor VIII (FVIII) or IX (FIX). In this study we evaluated the efficacy and safety of low-dose continuous infusion of FVIII or FIX. MATERIAL AND METHODS: We studied all eligible patients with HA or HB treated with continuous infusion of factor concentrates over an 18-year period in a single Slovenian Haemophilia Comprehensive Care Centre. Treatment started with a bolus injection of FVIII or FIX, followed by continuous infusion at the initial rate of 2 IU/kg/h of FVIII in HA patients and 4.5 IU/kg/h of FIX in HB patients. The infusion rate was subsequently adjusted according to the indication for therapy. RESULTS: A total of 66 continuous infusions (40 in major surgery, 10 in minor surgery and 16 with bleeding episode) in 46 HA patients and 16 (15 in severe and 1 in mild HA) in eight HB patients were included in the study. During the first week of treatment, the median continuous infusion rates in HA patients undergoing major surgery, minor surgery and a bleeding event were 2.18 (0.75-3.68), 1.48 (1.0-2.54) and 2.24 (1.33-3.93) IU/kg/h, respectively. The median FVIII activities were 0.69 (0.37-1.19), 0.47 (0.39-0.84) and 0.52 (0.36-1.06) IU/mL. After the first week of treatment, even lower doses of FVIII were needed. Red blood cell transfusions had to be administered to three patients (2 with severe and 1 with moderate HA) during the continuous infusion and inhibitors developed in five patients. In HB patients, the median continuous infusion rate was 1.85 (1.07-2.94) IU/kg/h and the median FIX activity was 0.62 (0.30-1.04) IU/mL. Red blood cell transfusions were not required, and thrombophlebitis and inhibitors did not appear. DISCUSSION: Overall, low-dose continuous infusion was shown to be an effective and safe way of treating patients with HA. The protocol used also proved efficient and safe in all HB patients. PMID- 26674821 TI - Carrion's disease after blood transfusion. PMID- 26674822 TI - Presence of anti-HBs antibodies in blood donors 18-22 years after vaccination and implications for the selection of candidates for plasmapheresis for the production of hyperimmune plasma. PMID- 26674823 TI - Evaluation of red blood cell and platelet antigen genotyping platforms (ID CORE XT/ID HPA XT) in routine clinical practice. AB - BACKGROUND: High-throughput genotyping platforms enable simultaneous analysis of multiple polymorphisms for blood group typing. BLOODchip(r) ID is a genotyping platform based on Luminex(r) xMAP technology for simultaneous determination of 37 red blood cell (RBC) antigens (ID CORE XT) and 18 human platelet antigens (HPA) (ID HPA XT) using the BIDS XT software. MATERIALS AND METHODS: In this international multicentre study, the performance of ID CORE XT and ID HPA XT, using the centres' current genotyping methods as the reference for comparison, and the usability and practicality of these systems, were evaluated under working laboratory conditions. DNA was extracted from whole blood in EDTA with Qiagen methodologies. Ninety-six previously phenotyped/genotyped samples were processed per assay: 87 testing samples plus five positive controls and four negative controls. RESULTS: Results were available for 519 samples: 258 with ID CORE XT and 261 with ID HPA XT. There were three "no calls" that were either caused by human error or resolved after repeating the test. Agreement between the tests and reference methods was 99.94% for ID CORE XT (9,540/9,546 antigens determined) and 100% for ID HPA XT (all 4,698 alleles determined). There were six discrepancies in antigen results in five RBC samples, four of which (in VS, N, S and Do(a)) could not be investigated due to lack of sufficient sample to perform additional tests and two of which (in S and C) were resolved in favour of ID CORE XT (100% accuracy). The total hands-on time was 28-41 minutes for a batch of 16 samples. Compared with the reference platforms, ID CORE XT and ID HPA XT were considered simpler to use and had shorter processing times. DISCUSSION: ID CORE XT and ID HPA XT genotyping platforms for RBC and platelet systems were accurate and user friendly in working laboratory settings. PMID- 26674824 TI - Blood banking-induced alteration of red blood cell oxygen release ability. AB - BACKGROUND: Current blood banking procedures may not fully preserve red blood cell (RBC) function during storage, contributing to the decrease of RBC oxygen release ability. This study was undertaken to evaluate the impact of routine cold storage on RBC oxygen release ability. MATERIALS AND METHODS: RBC units were collected from healthy donors and each unit was split into two parts (whole blood and suspended RBC) to exclude possible donor variability. Oxygen dissociation measurements were performed on blood units stored at 4 degrees C during a 5-week period. 2,3-diphosphoglycerate levels and fluorescent micrographs of erythrocyte band 3 were also analysed. RESULTS: P50 and oxygen release capacity decreased rapidly during the first 3 weeks, and then did not change significantly. In contrast, the kinetic properties (PO2-t curve and T*50) of oxygen release changed slowly during the first 3 weeks of storage, but then decreased significantly in the last 2 weeks. 2,3-diphosphoglycerate decreased quickly during the first 3 weeks of storage to almost undetectable levels. Band 3 aggregated significantly during the last 2 weeks of storage. DISCUSSION: RBC oxygen release ability appears to be sensitive to routine cold storage. The thermodynamic characteristics of RBC oxygen release ability changed mainly in the first 3 weeks of storage, due to the decrease of 2,3-diphosphoglycerate, whereas the kinetic characteristics of RBC oxygen release ability decreased significantly at the end of storage, probably affected by alterations of band 3. PMID- 26674826 TI - Rapid detection of DEHP in packed red blood cells stored under European and US standard conditions. PMID- 26674825 TI - The prognostic value of ABO blood group in cancer patients. AB - The antigens of the ABO system are expressed on red blood cell membranes as well as on the surface of several other normal and pathological cells and tissues. Following the first clinical observations more than 60 years ago, the role of ABO blood group in cancer biology has been intensely studied by several investigators, and it is now widely recognised that ABO antigens are associated with the risk of developing several types of tumours, namely pancreatic and gastric cancers. However, whether this association also affects the clinical outcome of cancer patients is less certain. In this narrative review, based on literature data, we discuss the role of ABO blood types as prognostic biomarkers in different types of cancers. The current knowledge of the underlying pathogenic mechanisms of the association is also analysed. PMID- 26674827 TI - Subclinical paroxysmal nocturnal haemoglobinuria associated with myelodysplastic syndrome: a case report. PMID- 26674829 TI - Hypoxanthine: a new paradigm to interpret the origin of transfusion toxicity. PMID- 26674830 TI - ABO blood group and neurodegenerative disorders: more than a casual association. PMID- 26674828 TI - Improving platelet transfusion safety: biomedical and technical considerations. AB - Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 degrees C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 degrees C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. PMID- 26674831 TI - Infectious agents, Leptospira spp. and Bartonella spp., in blood donors from Cajamarca, Peru. PMID- 26674832 TI - Coagulopathy and transfusion strategies in trauma. Overwhelmed by literature, supported by weak evidence. PMID- 26674834 TI - Deciphering Antigenic Determinants of Streptococcus pneumoniae Serotype 4 Capsular Polysaccharide using Synthetic Oligosaccharides. AB - Streptococcus pneumoniae is a major cause of mortality and morbidity worldwide. More than 90 S. pneumoniae serotypes are distinguished based on the structure of their primary targets to the human immune system, the capsular polysaccharides (CPSs). The CPS of the prevalent serotype 4 (ST4) is composed of tetrasaccharide repeating units and is included in existing pneumococcal vaccines. Still, the structural antigenic determinants that are essential for protective immunity, including the role of the rare and labile cyclic trans-(2,3) pyruvate ketal modification, remain largely unknown. Molecular insights will support the design of synthetic subunit oligosaccharide vaccines. Here, we identified the key antigenic determinants of ST4 CPS with the help of pyruvated and nonpyruvated synthetic repeating unit glycans. Glycan arrays revealed oligosaccharide antigens recognized by antibodies in the human reference serum. Selected depyruvated ST4 oligosaccharides were used to formulate neoglycoconjugates and immunologically evaluated in mice. These oligosaccharides were highly immunogenic, but the resulting antiglycan antibodies showed only limited binding to the natural CPS present on the bacterial surface. Glycan array and surface plasmon resonance analysis of murine polyclonal serum antibodies as well as monoclonal antibodies revealed that terminal sugars are important in directing the immune responses. The pyruvate modification on the oligosaccharide is needed for cross-reactivity with the native CPS. These findings are an important step toward the design of oligosaccharide-based vaccines against S. pneumoniae ST4. PMID- 26674833 TI - Deterioration of red blood cell mechanical properties is reduced in anaerobic storage. AB - BACKGROUND: Hypothermic storage of red blood cells (RBCs) results in progressive deterioration of the rheological properties of the cells, which may reduce the efficacy of RBC transfusions. Recent studies have suggested that storing RBC units under anaerobic conditions may reduce this storage-induced deterioration. MATERIALS AND METHODS: The aim of this study was to compare the rheological properties of conventionally and anaerobically stored RBC and provide a measure of the relationship between oxidative damage to stored RBC and their ability to perfuse microvascular networks. Three different microfluidic devices were used to measure the ability of both types of stored RBC to perfuse artificial microvascular networks. Flow rates of the RBC passing through the entire network (bulk perfusion) and the individual capillaries (capillary perfusion) of the devices were measured on days 2, 21, 42, and 63 of storage. RESULTS: The bulk perfusion rates for anaerobically stored RBC were significantly higher than for conventionally stored RBCs over the entire duration of storage for all devices (up to 10% on day 42; up to 14% on day 63). Capillary perfusion rates suggested that anaerobically stored RBC units contained significantly fewer non-deformable RBC capable of transiently plugging microfluidic device capillaries. The number of plugging events caused by these non-deformable RBC increased over the 63 days of hypothermic storage by nearly 16- to 21-fold for conventionally stored units, and by only about 3- to 6-fold for anaerobically stored units. DISCUSSION: The perfusion measurements suggest that anaerobically stored RBC retain a greater ability to perfuse networks of artificial capillaries compared to conventionally (aerobically) stored RBC. It is likely that anaerobic storage confers this positive effect on the bulk mechanical properties of stored RBC by significantly reducing the number of non-deformable cells present in the overall population of relatively well-preserved RBC. PMID- 26674835 TI - Change in size, morphology and stability of DNA polyplexes with hyperbranched poly(ethyleneimines) containing bulky maltose units. AB - Polyplexes between Salmon DNA and non-modified hyperbranched poly(ethyleneimines) of varying molar mass, i.e., PEI(5 k) with 5000 g/mol and PEI(25 k) with 25,000 g/mol, and modified PEI(5 k) with maltose units (PEI-Mal) were investigated in dependence on the molar N/P ratio by using dynamic light scattering (DLS), zeta potential measurements, micro differential scanning calorimetry (MU-DSC), scanning-transmission electron microscopy (STEM), and cryo-scanning electron microscopy (cryo-SEM). A reloading of the polyplexes can be observed by adding the unmodified PEI samples of different molar mass. In excess of PEI a morphological transition from core-shell particles (at N/P 8) to loosely packed onion-like polyplexes (at N/P 40) is observed. The shift of the DSC melting peak from 88 degrees C to 76 degrees C indicates a destabilization of the DNA double helix due to the complexation with the unmodified PEI. Experiments with the maltose-modified PEI show a reloading already at a lower N/P ratio. Due to the presence of the sugar units in the periphery of the polycation electrostatic interactions between DNA become weaker, but cooperative H-bonding forces are reinforced. The resulting less-toxic, more compact polyplexes in excess of the PEI-Mal with two melting points and well distributed DNA segments are of special interest for extended gene delivery experiments. PMID- 26674836 TI - Bioinspired lubricating films of cellulose nanofibrils and hyaluronic acid. AB - The development of materials that combine the excellent mechanical strength of cellulose nanofibrils (CNF) with the lubricating properties of hyaluronic acid (HA) is a new, promising approach to cartilage implants not explored so far. A simple, solvent-free method to produce a very lubricating, strong cellulosic material by covalently attaching HA to the surface of CNF films is described in this work. A detailed analysis of the tribological properties of the CNF films with and without HA is also presented. Surface and friction forces at micro/nanoscale between model hard surfaces (glass microspheres) and the CNF thin films were measured using an atomic force microscope and the colloid probe technique. The effect of HA attachment, the pH and the ionic strength of the aqueous medium on the forces was examined. Excellent lubrication was observed for CNF films with HA attached in conditions where the HA layer was highly hydrated. These results pave the way for the development of new nanocellulose-based materials with good lubrication properties that could be used in biomedical applications. PMID- 26674837 TI - Alginate/magnetite hybrid beads for magnetically stimulated release of dopamine. AB - Hybrid beads composed of magnetite nanoparticles (MNP) and alginate (Alg) were synthesized and coded as Alg-MNP. They were incubated in dopamine (DOPA) solution (5 g/L), at pH 7.4 and 8 degrees C, during 12 h, promoting the DOPA loaded magnetic beads, coded as Alg-MNP/DOPA. The release of DOPA was further evaluated in the absence and the presence of external magnetic field (EMF) of 0.4 T. The products Alg-MNP and Alg-MNP/DOPA were characterized by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared vibrational spectroscopy (FTIR), UV spectrophotometry, thermogravimetric analyses (TGA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) analyses and superconducting quantum interference device (SQUID) magnetometer. The magnetic and chemical properties of Alg-MNP beads were not affected by DOPA loading. The incorporation of DOPA into the beads depended on the pH and on the negative charge density. At pH 7.4 38% of DOPA were loaded into Alg-MNP beads, whereas at pH 2 or using neat Alg beads (lower charge density than Alg-MNP) the loading efficiency decreased to one third or less. In the absence of EMF, 24% of the loaded DOPA was released from Alg-MNP at pH 7.4 over a period of 26 h. The released amount increased to 33% under the stimulus of EMF. A model was proposed to explain the loading efficiency of charged drugs, as DOPA, into hybrid beads and the role played by EMF on delivery systems, where drug and matrix are oppositely charged. The results suggest that the alginate combined with magnetite nanoparticles is a promising system for release of DOPA in the presence of EMF. PMID- 26674838 TI - Bactericidal activity and mechanism of AgI/AgBr/BiOBr(0.75)I(0.25) under visible light irradiation. AB - The AgI/AgBr/BiOBr0.75I0.25 nanocomposites were synthesized by a solvothermal process, followed by an in-situ ion exchange reaction. The disinfection activities of the as-synthesized photocatalyst to model cell type, Gram-negative Escherichia coli (E. coli), were investigated under visible light irradiation condition (lambda>=400 nm). Results showed that 80 mg/L AgI/AgBr/BiOBr0.75I0.25 could completely inactivate 3*10(7) CFU mL(-1)E. coli cells within 30 min under visible light irradiation. Moreover, the bactericidal mechanisms involved in the photocatalytic disinfection process were systematically investigated. Ag(+) ions released from the nanocomposites negligibly contributed to the bactericidal activity, while active species including h(+), e(-) and .O2(-) played important roles in the disinfection system. Direct contact of bacterial cells and nanoparticles was found to be the prerequisite for both the generation of .O2(-) and the disinfection processes. The disruption of cell membrane and emission of cytoplasm directly inactivated E. coli cells. In addition, AgI/AgBr/BiOBr0.75I0.25 exhibited strong antibacterial activity toward E. coli even in four consecutive reused cycles. PMID- 26674839 TI - Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret. AB - A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects. PMID- 26674840 TI - PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine based surfactant for pH-triggered doxorubicin release. AB - The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy. PMID- 26674841 TI - pH-sensitive polymeric cisplatin-ion complex with styrene-maleic acid copolymer exhibits tumor-selective drug delivery and antitumor activity as a result of the enhanced permeability and retention effect. AB - Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA-CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA-CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA-CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA-CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA-CDDP than of free CDDP. SMA-CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg*3 caused a weight loss of more than 5%; SMA-CDDP at 60 mg/kg (CDDP equivalent)*3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA-CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP. PMID- 26674842 TI - Budesonide-hydroxypropyl-beta-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels. AB - Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-beta-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-beta-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc=8662.8 M(-1)), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-beta-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-beta-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (Tm) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-beta-CD or BUD:HP beta-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-beta-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-beta CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis. PMID- 26674843 TI - Prehospital Spinal Immobilization: Effect of Effort on Kinematics of Voluntary Head-neck Motion Assessed using Accelerometry. AB - INTRODUCTION: Standards for immobilizing potentially spine-injured patients in the prehospital environment are evolving. Current guidelines call for more research into treatment practices. Available research into spinal immobilization (SI) reveals a number of limitations. PROBLEM: There are currently few techniques for measuring head and neck motion that address identified limitations and can be adapted to clinically relevant scenarios. This study investigates one possible method. METHODS: Study participants were fitted with miniaturized accelerometers to record head motion. Participants were exposed to three levels of restraint: none, cervical-collar only, and full immobilization. In each condition, participants were instructed to move in single planes, with multiple iterations at each of four levels of effort. Participants were also instructed to move continuously in multiple planes, with iterations at each of three levels of simulated patient movement. Peak and average displacement and acceleration were calculated for each immobilization condition and level of effort. Comparisons were made with video-based measurement. Participant characteristics also were tracked. RESULTS: Acceleration and displacement of the head increased with effort and decreased with more restraint. In some conditions, participants generated measurable acceleration with minimal displacement. Continuous, multi-dimensional motions produced greater displacement and acceleration than single-plane motions under similar conditions. CONCLUSION: Study results suggest a number of findings: acceleration complements displacement as a measure of motion in potentially spine injured patients; participant effort has an effect on outcome measures; and continuous, multi-dimensional motion can produce results that differ from single plane motions. Miniaturized accelerometers are a promising technology for future research to investigate these findings in realistic, clinically relevant scenarios. PMID- 26674844 TI - Effect of Interleukin-10 and Laminar Shear Stress on Endothelial Nitric Oxide Synthase and Nitric Oxide in African American Human Umbilical Vein Endothelial Cells. AB - BACKGROUND: African Americans have a predisposition to heightened systemic inflammation and a high prevalence of hypertension. OBJECTIVE: The purpose of this study was to evaluate the influence of interleukin-10 (IL-10) and laminar shear stress (LSS) on African American endothelial cells by measuring total endothelial nitric oxide synthase (eNOS) protein expression and its phosphorylated form (p-eNOS) at Serine 1177, and nitric oxide (NO) levels, in response to IL-10 incubation and high physiological levels of LSS, used as an in vitro mimetic for aerobic exercise training (AEXT). DESIGN: Human umbilical vein endothelial cells (HUVEC) from an African American donor were cultured. The experimental conditions included Static, Static with IL-10 Incubation, LSS at 20 dynes/cm2, and LSS at 20 dynes/cm2 with IL-10 Incubation. Western blotting was used to measure eNOS and p-eNOS protein expression in the cells. A modified Griess assay was used to measure NO metabolites in the cell culture media. RESULTS: There were significant increases in p-eNOS, eNOS, and NO in the LSS at 20 dynes/cm2 and LSS at 20 dynes/cm2 with IL-10 Incubation experimental conditions when compared to the Static experimental condition. There were no other statistically significant differences demonstrating that IL-10 did not have an additive effect on eNOS activity in our study. CONCLUSION: The significant increases in p-eNOS, eNOS, and NO as a result of LSS in African American HUVECs suggest that AEXT may be a viable, nonpharmacologic method to improve vascular inflammation status and vasodilation, and thereby contribute to hypertension reduction in the African American population. PMID- 26674846 TI - Pyrrolo-[3,2-b]pyrroles for Photochromic Analysis of Halocarbons. AB - Dramatic photochromic-change of 2,5-bis(triphenylamine)-substituted N,N' diphenylpyrrolo-[3,2-b]pyrrole (1) with halocarbons provides an effective route for halocarbon analysis with the naked eye. The visual detection range can reach as low as 10(-4) ~ 10(-5) M (1-10 ppm) in CH3CN. This method can also be applied for detection of CHCl3 in water. Fabrication of a disposable paper test cartridge along with using a camera flash as the light source allows on-site halocarbon detection in seconds. Quantitative analysis for CHCl3 and CH2Cl2 have also been demonstrated. PMID- 26674845 TI - Corrigendum: Rare coding variants and X-linked loci associated with age at menarche. PMID- 26674847 TI - Scrotal imaging. AB - Pathological lesions within the scrotum are relatively rare in imaging except for ultrasonography. The diseases presented in the paper are usually found in men at the age of 15-45, i.e. men of reproductive age, and therefore they are worth attention. Scrotal ultrasound in infertile individuals should be conducted on a routine basis owing to the fact that pathological scrotal lesions are frequently detected in this population. Malignant testicular cancers are the most common neoplasms in men at the age of 20-40. Ultrasound imaging is the method of choice characterized by the sensitivity of nearly 100% in the differentiation between intratesticular and extratesticular lesions. In the case of doubtful lesions that are not classified for intra-operative verification, nuclear magnetic resonance is applied. Computed tomography, however, is performed to monitor the progression of a neoplastic disease, in pelvic trauma with scrotal injury as well as in rare cases of scrotal hernias involving the ureters or a fragment of the urinary bladder. PMID- 26674850 TI - Excitonic Diffusion in InGaN/GaN Core-Shell Nanowires. AB - We report on the direct observation of the diffusion of carriers in graded InGaN/GaN quantum wells in a nanowire. By probing the local dynamics at the nanoscale, along the wire for different temperatures between 4 and 250 K, we conclude that this diffusion process is thermally activated. In addition, the analysis of the cathodoluminescence lifetime for different temperatures shows that the carrier motion is isotropic and does not follow the indium gradient. Our observations are interpreted in terms of a hopping process between localized states. We find that the random alloy fluctuations prevent any directional drift of excitons along the In gradient and therefore any carrier accumulation. Our results therefore confirm the potential of core-shell nanowires for lighting devices. Indeed, the short lifetime of m-plane quantum wells together with their large active area and the homogeneous distribution of carrier along the quantum well will decrease influence of any high carrier density effect on the efficiency of these light-emitting diodes. PMID- 26674849 TI - Diagnostic value of ultrasound indicators of neoplastic risk in preoperative differentiation of adnexal masses. AB - AIM: To assess the diagnostic value of the risk of malignancy indices and simple ultrasound- based rules in preoperative differentiation of adnexal masses. MATERIAL AND METHODS: Retrospective examination of 87 patients admitted to hospital due to adnexal tumors. The lesions were evaluated on the basis of international ultrasound classification of ovarian tumors and four risk of malignancy indices were calculated based on ultrasound examination, concentration of CA 125 and menopausal status. RESULTS: The patients were aged between 17 and 79, the mean age was 44.5 (standard deviation SD=16.6). Most of the patients (60.91%) were before their menopause. The sensitivity of the simple ultrasound based rules in the diagnosis of malignancies equaled 64.71% and the specificity constituted 90.00%. A significant statistical difference in the presence of the malignant process was demonstrated in relation to age, menopausal status, CA 125 concentration and analyzed ultrasound score. All indices were characterized by similar sensitivity and specificity. The highest specificity and predictive value of malignant lesions out of the assessed ones was demonstrated by the risk of malignancy index proposed by Yamamoto. The risk of malignancy index according to Jacobs, however, showed the highest predictive value in the case of non-malignant lesions. CONCLUSIONS: The multiparametric ultrasound examination may facilitate the selection of patients with adnexal tumors to provide them with an appropriate treatment - observation, laparotomy and laparoscopy. These parameters constitute a simple ambulatory method of determining the character of adnexal masses before recommending appropriate treatment. PMID- 26674851 TI - Multiple HPV-Induced Squamous Cell Carcinomas on the Fingers of a Patient with Systemic Lupus Erythematosus: A Case and Review. AB - Human papilloma virus (HPV) infection is documented to be involved in the development of epithelial malignancies, mostly in cervical cancer. Systemic lupus erythematosus (SLE) patients have an increased prevalence of such an infection. We report the case of a 55-year-old female SLE patient who developed multiple in situ squamous cell carcinomas on her fingers, after chronic HPV infection. HPV-33 DNA was isolated from the lesions. The purpose of this case presentation is to raise awareness about HPV-induced malignancies for this high-risk group and propose an early HPV vaccination to efficiently prevent such comorbidities. PMID- 26674853 TI - Prof. Randall Starling: left ventricular assist device therapy for advanced heart failure. PMID- 26674848 TI - Skeletal muscle as a therapeutic target for delaying type 1 diabetic complications. AB - Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease targeting the pancreatic beta-cells and rendering the person hypoinsulinemic and hyperglycemic. Despite exogenous insulin therapy, individuals with T1DM will invariably develop long-term complications such as blindness, kidney failure and cardiovascular disease. Though often overlooked, skeletal muscle is also adversely affected in T1DM, with both physical and metabolic derangements reported. As the largest metabolic organ in the body, impairments to skeletal muscle health in T1DM would impact insulin sensitivity, glucose/lipid disposal and basal metabolic rate and thus affect the ability of persons with T1DM to manage their disease. In this review, we discuss the impact of T1DM on skeletal muscle health with a particular focus on the proposed mechanisms involved. We then identify and discuss established and potential adjuvant therapies which, in association with insulin therapy, would improve the health of skeletal muscle in those with T1DM and thereby improve disease management- ultimately delaying the onset and severity of other long-term diabetic complications. PMID- 26674852 TI - Effect of Occupational Exposure on Blood Cell Counts, Electrocardiogram and Blood Pressure in Rice Mill Workers. AB - INTRODUCTION: Under normal conditions, parasympathetic and sympathetic nervous systems interact to regulate the heart rate of about 70 beats per minute. Activation of sympathetic nervous system by emotional or physical stress increases heart rate and the force of heart beat. There are many factors which alter the heart rate. The chemical and mechanical stimulation of receptors can also cause change in blood pressure through autonomic nervous system. Exposure to dust also causes alteration in blood cell counts. This can be due to allergic reactions and inflammation which in turn evoked by dust entering the lungs. OBJECTIVES: Aim of the study was to evaluate the effect of occupational exposure on haematological and cardiovascular parameters of rice mill workers by analysing Blood Cell Counts, ECG and Blood Pressure. MATERIALS AND METHODS: This cross sectional study was carried on 134 rice mill workers and an equal number of age and sex matched healthy individual. The blood cell counts were determined by automated cell counter machine, ECG was recorded by using ECG machine and Blood Pressure was measured by using mercurial sphygmomanometer. RESULTS: Neurtrophil, Eosinophil and Lymphocyte count among haematological parameters were significantly increased in exposed individuals. Marked variation was seen in ECG and Blood pressure among cardiovascular parameters of exposed individuals compared with control group. CONCLUSION: The findings of our study clearly indicate that the rice mill workers are under high level of dust exposure which has deleterious effects on their blood and tissues. It is due to high oxidative stress. There are abnormalities seen in cardiovascular system. PMID- 26674854 TI - Effect of edge pruning on structural controllability and observability of complex networks. AB - Controllability and observability of complex systems are vital concepts in many fields of science. The network structure of the system plays a crucial role in determining its controllability and observability. Because most naturally occurring complex systems show dynamic changes in their network connectivity, it is important to understand how perturbations in the connectivity affect the controllability of the system. To this end, we studied the control structure of different types of artificial, social and biological neuronal networks (BNN) as their connections were progressively pruned using four different pruning strategies. We show that the BNNs are more similar to scale-free networks than to small-world networks, when comparing the robustness of their control structure to structural perturbations. We introduce a new graph descriptor, 'the cardinality curve', to quantify the robustness of the control structure of a network to progressive edge pruning. Knowing the susceptibility of control structures to different pruning methods could help design strategies to destroy the control structures of dangerous networks such as epidemic networks. On the other hand, it could help make useful networks more resistant to edge attacks. PMID- 26674856 TI - Global and Specific Motor Inhibitory Mechanisms during Action Preparation. PMID- 26674855 TI - Enantioselective Rh-Catalyzed Carboacylation of C?N Bonds via C-C Activation of Benzocyclobutenones. AB - Herein we describe the first enantioselective Rh-catalyzed carboacylation of oximes (imines) via C-C activation. In this transformation, the benzocyclobutenone C1-C2 bond is selectively activated by a low valent rhodium catalyst and subsequently the resulting two Rh-C bonds add across a C?N bond, which provides a unique approach to access chiral lactams. A range of polycyclic nitrogen-containing scaffolds were obtained in good yields with excellent enantioselectivity. Further derivatization of the lactam products led to a rapid entry to various novel fused heterocycles. PMID- 26674857 TI - The Neural Mechanisms of Bayesian Belief Updating. PMID- 26674859 TI - Acetylcholine from Visual Circuits Modulates the Activity of Arousal Neurons in Drosophila. AB - Drosophila melanogaster's large lateral ventral neurons (lLNvs) are part of both the circadian and sleep-arousal neuronal circuits. In the past, electrophysiological analysis revealed that lLNvs fire action potentials (APs) in bursting or tonic modes and that the proportion of neurons firing in those specific patterns varies circadianly. Here, we provide evidence that lLNvs fire in bursts both during the day and at night and that the frequency of bursting is what is modulated in a circadian fashion. Moreover, we show that lLNvs AP firing is not only under cell autonomous control, but is also modulated by the network, and in the process we develop a novel preparation to assess this. We demonstrate that lLNv bursting mode relies on a cholinergic input because application of nicotinic acetylcholine receptor antagonists impairs this firing pattern. Finally, we found that bursting of lLNvs depends on an input from visual circuits that includes the cholinergic L2 monopolar neurons from the lamina. Our work sheds light on the physiological properties of lLNvs and on a neuronal circuit that may provide visual information to these important arousal neurons. SIGNIFICANCE STATEMENT: Circadian rhythms are important for organisms to be able to anticipate daily changes in environmental conditions to adjust physiology and behavior accordingly. These rhythms depend on an endogenous mechanism that operates in dedicated neurons. In the fruit fly, the large lateral ventral neurons (lLNvs) are part of both the circadian and sleep-arousal neuronal circuits. Here, we provide new details about the firing properties of these neurons and demonstrate that they depend, not only on cell-autonomous mechanisms, but also on a specific neurotransmitter derived from visual circuits. Our work sheds light on the physiological properties of lLNvs and on a neuronal circuit that may provide visual information to these important arousal neurons. PMID- 26674858 TI - Heading Tuning in Macaque Area V6. AB - Cortical areas, such as the dorsal subdivision of the medial superior temporal area (MSTd) and the ventral intraparietal area (VIP), have been shown to integrate visual and vestibular self-motion signals. Area V6 is interconnected with areas MSTd and VIP, allowing for the possibility that V6 also integrates visual and vestibular self-motion cues. An alternative hypothesis in the literature is that V6 does not use these sensory signals to compute heading but instead discounts self-motion signals to represent object motion. However, the responses of V6 neurons to visual and vestibular self-motion cues have never been studied, thus leaving the functional roles of V6 unclear. We used a virtual reality system to examine the 3D heading tuning of macaque V6 neurons in response to optic flow and inertial motion stimuli. We found that the majority of V6 neurons are selective for heading defined by optic flow. However, unlike areas MSTd and VIP, V6 neurons are almost universally unresponsive to inertial motion in the absence of optic flow. We also explored the spatial reference frames of heading signals in V6 by measuring heading tuning for different eye positions, and we found that the visual heading tuning of most V6 cells was eye-centered. Similar to areas MSTd and VIP, the population of V6 neurons was best able to discriminate small variations in heading around forward and backward headings. Our findings support the idea that V6 is involved primarily in processing visual motion signals and does not appear to play a role in visual-vestibular integration for self-motion perception. SIGNIFICANCE STATEMENT: To understand how we successfully navigate our world, it is important to understand which parts of the brain process cues used to perceive our direction of self-motion (i.e., heading). Cortical area V6 has been implicated in heading computations based on human neuroimaging data, but direct measurements of heading selectivity in individual V6 neurons have been lacking. We provide the first demonstration that V6 neurons carry 3D visual heading signals, which are represented in an eye centered reference frame. In contrast, we found almost no evidence for vestibular heading signals in V6, indicating that V6 is unlikely to contribute to multisensory integration of heading signals, unlike other cortical areas. These findings provide important constraints on the roles of V6 in self-motion perception. PMID- 26674860 TI - Intertrial Variability in the Premotor Cortex Accounts for Individual Differences in Peripersonal Space. AB - We live in a dynamic environment, constantly confronted with approaching objects that we may either avoid or be forced to address. A multisensory and sensorimotor interface, the peripersonal space (PPS), mediates every physical interaction between our body and the environment. Behavioral investigations show high variability in the extension of PPS across individuals, but there is a lack of evidence on the neural underpinnings of these large individual differences. Here, we used approaching auditory stimuli and fMRI to capture the individual boundary of PPS and examine its neural underpinnings. Precisely, we tested the hypothesis that intertrial variability (ITV) in brain regions coding PPS predicts individual differences of its boundary at the behavioral level. Selectively in the premotor cortex, we found that ITV, rather than trial-averaged amplitude, of BOLD responses to far rather than near dynamic stimuli predicts the individual extension of PPS. Our results provide the first empirical support for the relevance of ITV of brain responses for individual differences in human behavior. SIGNIFICANCE STATEMENT: Peripersonal space (PPS) is a multisensory and sensorimotor interface mediating every physical interaction between the body and the environment. A major characteristic of the boundary of PPS in humans is the extremely high variability of its location across individuals. We show that interindividual differences in the extension of the PPS are predicted by variability of BOLD responses in the premotor cortex to far stimuli approaching our body. Our results provide the first empirical support to the relevance of variability of evoked responses for human behavior and its variance across individuals. PMID- 26674861 TI - Corticostriatal Divergent Function in Determining the Temporal and Spatial Properties of Motor Tics. AB - Striatal disinhibition leads to the formation of motor tics resembling those expressed during Tourette syndrome and other tic disorders. The spatial properties of these tics are dependent on the location of the focal disinhibition within the striatum; however, the factors affecting the temporal properties of tic expression are still unknown. Here, we used microstimulation within the motor cortex of freely behaving rats before and after striatal disinhibition to explore the factors underlying the timing of individual tics. Cortical activation determined the timing of individual tics via an accumulation process of inputs that was dependent on the frequency and amplitude of the inputs. The resulting tics and their neuronal representation within the striatum were highly stereotypic and independent of the cortical activity properties. The generation of tics was limited by absolute and relative tic refractory periods that were derived from an internal striatal state. Thus, the precise time of the tic expression depends on the interaction between the summation of incoming excitatory inputs to the striatum and the timing of the previous tic. A data driven computational model of corticostriatal function closely replicated the temporal properties of tic generation and enabled the prediction of tic timing based on incoming cortical activity and tic history. These converging experimental and computational findings suggest a clear functional dichotomy within the corticostriatal network, pointing to disparate temporal (cortical) versus spatial (striatal) encoding. Thus, the abnormal striatal inhibition typical of Tourette syndrome and other tic disorders results in tics due to cortical activation of the abnormal striatal network. SIGNIFICANCE STATEMENT: The factors underlying the temporal properties of tics expressed in Tourette syndrome and other tic disorders have eluded clinicians and scientists for decades. In this study, we highlight the key role of corticostriatal activity in determining the timing of individual tics. We found that cortical activation determined the timing of tics but did not determine their form. A data-driven computational model of the corticostriatal network closely replicated the temporal properties of tic generation and enabled the prediction of tic timing based on incoming cortical activity and tic history. This study thus shows that, although tics originate in the striatum, their timing depends on the interplay between incoming excitatory corticostriatal inputs and the internal striatal state. PMID- 26674862 TI - Perceptual Integration Deficits in Autism Spectrum Disorders Are Associated with Reduced Interhemispheric Gamma-Band Coherence. AB - The integration of visual details into a holistic percept is essential for object recognition. This integration has been reported as a key deficit in patients with autism spectrum disorders (ASDs). The weak central coherence account posits an altered disposition to integrate features into a coherent whole in ASD. Here, we test the hypothesis that such weak perceptual coherence may be reflected in weak neural coherence across different cortical sites. We recorded magnetoencephalography from 20 adult human participants with ASD and 20 matched controls, who performed a slit-viewing paradigm, in which objects gradually passed behind a vertical or horizontal slit so that only fragments of the object were visible at any given moment. Object recognition thus required perceptual integration over time and, in case of the horizontal slit, also across visual hemifields. ASD participants were selectively impaired in the horizontal slit condition, indicating specific difficulties in long-range synchronization between the hemispheres. Specifically, the ASD group failed to show condition-related enhancement of imaginary coherence between the posterior superior temporal sulci in both hemispheres during horizontal slit-viewing in contrast to controls. Moreover, local synchronization reflected in occipitocerebellar beta-band power was selectively reduced for horizontal compared with vertical slit-viewing in ASD. Furthermore, we found disturbed connectivity between right posterior superior temporal sulcus and left cerebellum. Together, our results suggest that perceptual integration deficits co-occur with specific patterns of abnormal global and local synchronization in ASD. SIGNIFICANCE STATEMENT: The weak central coherence account proposes a tendency of individuals with autism spectrum disorders (ASDs) to focus on details at the cost of an integrated coherent whole. Here, we provide evidence, at the behavioral and the neural level, that visual integration in object recognition is impaired in ASD, when details had to be integrated across both visual hemifields. We found enhanced interhemispheric gamma-band coherence in typically developed participants when communication between cortical hemispheres was required by the task. Importantly, participants with ASD failed to show this enhanced coherence between bilateral posterior superior temporal sulci. The findings suggest that visual integration is disturbed at the local and global synchronization scale, which might bear implications for object recognition in ASD. PMID- 26674863 TI - Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress. AB - Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. SIGNIFICANCE STATEMENT: Women have a higher incidence of depression than men. However, preclinical models, the first step in developing new diagnostics and therapeutics, have been performed mainly on male subjects. Using a stress-based animal model of depression that causes behavioral effects in females but not males, we demonstrate a sex-specific transcriptional profile in brain reward circuitry. This transcriptional profile can be altered by removal of an epigenetic mechanism, which normally suppresses DNA transcription, creating a hybrid male/female transcriptional pattern. Removal of this epigenetic mechanism also induces behavioral resilience to stress in females. These findings shed new light onto molecular factors controlling sex differences in stress response. PMID- 26674864 TI - A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1. AB - An important function of glia is the maintenance of the ionic composition and pH of the synaptic microenvironment. In terms of pH regulation, HCO3 (-) buffering has been shown to be important in both glia and neurons. Here, we used in vivo fluorescent pH imaging and RNA sequencing of the amphid sheath glia of Caenorhabditis elegans to reveal a novel mechanism of cellular HCO3 (-) uptake. While the classical mechanism of HCO3 (-) uptake involves Na(+)/HCO3 (-) cotransporters, here we demonstrate that the C. elegans ClC Cl(-) channel CLH-1 is highly permeable to HCO3 (-) and mediates HCO3 (-) uptake into amphid sheath glia. CLH-1 has homology and electrophysiological properties similar to the mammalian ClC-2 Cl(-) channel. Our data suggest that, in addition to maintaining synaptic Cl(-) concentration, these channels may also be involved in maintenance of synaptic pH via HCO3 (-) flux. These findings provide an exciting new facet of study regarding how pH is regulated in the brain. SIGNIFICANCE STATEMENT: Maintenance of pH is essential for the physiological function of the nervous system. HCO3 (-) is crucial for pH regulation and is transported into the cell via ion transporters, including ion channels, the molecular identity of which remains unclear. In this manuscript, we describe our discovery that the C. elegans amphid sheath glia regulate intracellular pH via HCO3 (-) flux through the voltage-gated ClC channel CLH-1. This represents a novel function for ClC channels, which has implications for their possible role in mammalian glial pH regulation. This discovery may also provide a novel therapeutic target for pathologic conditions, such as ischemic stroke where acidosis leads to widespread death of glia and subsequently neurons. PMID- 26674865 TI - The Occipital Face Area Is Causally Involved in Facial Viewpoint Perception. AB - Humans reliably recognize faces across a range of viewpoints, but the neural substrates supporting this ability remain unclear. Recent work suggests that neural selectivity to mirror-symmetric viewpoints of faces, found across a large network of visual areas, may constitute a key computational step in achieving full viewpoint invariance. In this study, we used repetitive transcranial magnetic stimulation (rTMS) to test the hypothesis that the occipital face area (OFA), putatively a key node in the face network, plays a causal role in face viewpoint symmetry perception. Each participant underwent both offline rTMS to the right OFA and sham stimulation, preceding blocks of behavioral trials. After each stimulation period, the participant performed one of two behavioral tasks involving presentation of faces in the peripheral visual field: (1) judging the viewpoint symmetry; or (2) judging the angular rotation. rTMS applied to the right OFA significantly impaired performance in both tasks when stimuli were presented in the contralateral, left visual field. Interestingly, however, rTMS had a differential effect on the two tasks performed ipsilaterally. Although viewpoint symmetry judgments were significantly disrupted, we observed no effect on the angle judgment task. This interaction, caused by ipsilateral rTMS, provides support for models emphasizing the role of interhemispheric crosstalk in the formation of viewpoint-invariant face perception. SIGNIFICANCE STATEMENT: Faces are among the most salient objects we encounter during our everyday activities. Moreover, we are remarkably adept at identifying people at a glance, despite the diversity of viewpoints during our social encounters. Here, we investigate the cortical mechanisms underlying this ability by focusing on effects of viewpoint symmetry, i.e., the invariance of neural responses to mirror symmetric facial viewpoints. We did this by temporarily disrupting neural processing in the occipital face area (OFA) using transcranial magnetic stimulation. Our results demonstrate that the OFA causally contributes to judgments facial viewpoints and suggest that effects of viewpoint symmetry, previously observed using fMRI, arise from an interhemispheric integration of visual information even when only one hemisphere receives direct visual stimulation. PMID- 26674866 TI - Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons. AB - Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT: This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both channel types participate in action potential repolarization about equally, they have contrasting and partially opposite effects in regulating neuronal firing at frequencies typical of bursting. Our analysis shows that this results from their different kinetic properties, with fast-activating BK channels serving to short circuit activation of Kv2 channels, which tend to slow firing by producing a deep afterhyperpolarization. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. PMID- 26674868 TI - Role of IL-10 in Resolution of Inflammation and Functional Recovery after Peripheral Nerve Injury. AB - A rapid proinflammatory response after peripheral nerve injury is required for clearance of tissue debris (Wallerian degeneration) and effective regeneration. Unlike the CNS, this response is rapidly terminated in peripheral nerves starting between 2 and 3 weeks after crush injury. We examined the expression and role of the anti-inflammatory cytokine IL-10 in the resolution of inflammation and regeneration after sciatic nerve crush injury in mice. IL-10 mRNA increased over the first 7 d after injury, whereas at the protein level, immunofluorescence labeling showed IL-10(+) cells increased almost 3-fold in the first 3 weeks, with macrophages being the major cell type expressing IL-10. The role of IL-10 in nerve injury was assessed using IL-10-null mice. Increased numbers of macrophages were found in the distal segment of IL-10-null mice at early (3 d) and late (14 and 21 d) time points, suggesting that IL-10 may play a role in controlling the early influx and the later efflux of macrophages out of the nerve. A chemokine/cytokine PCR array of the nerve 24 h after crush showed a 2- to 4-fold increase in the expression of 10 proinflammatory mediators in IL-10(-/-) mice. In addition, myelin phagocytosis in vitro by LPS stimulated bone-marrow-derived macrophages from IL-10-null mice failed to downregulate expression of proinflammatory chemokines/cytokines, suggesting that IL-10 is required for the myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti inflammatory/pro-repair phenotype. The failure to switch off inflammation in IL 10-null mice was accompanied by impaired axon regeneration and poor recovery of motor and sensory function. SIGNIFICANCE STATEMENT: An appropriately regulated inflammatory response after peripheral nerve injury is essential for axon regeneration and recovery. The aim of this study was to investigate the expression and role of the anti-inflammatory cytokine IL-10 in terminating inflammation after sciatic nerve crush injury and promoting regeneration. IL-10 is rapidly expressed by macrophages after crush injury. Its role was assessed using IL-10-null mice, which showed that IL-10 plays a role in controlling the early influx and the later efflux of macrophages out of the injured nerve, reduces the expression of proinflammatory chemokines and cytokines, and is required for myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory. Furthermore, lack of IL-10 leads to impaired axon regeneration and poor recovery of motor and sensory function. PMID- 26674867 TI - Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception. AB - Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS (1)H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT: Our study describes a decrease in cholinergic neurotransmission in the posterior insular cortex in neuropathic pain condition and the involvement of M2 receptors. Targeting these cortical muscarinic M2 receptors using central cholinomimetics could be an effective therapy for neuropathic pain treatment. PMID- 26674869 TI - Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST Associated Chromatin-Modifying Proteins. AB - Ischemia induces extensive temporal changes in cerebral transcriptome that influences the neurologic outcome after stroke. In addition to protein-coding RNAs, many classes of noncoding RNAs, including long noncoding RNAs (LncRNAs), also undergo changes in the poststroke brain. We currently evaluated the functional significance of an LncRNA called Fos downstream transcript (FosDT) that is cogenic with Fos gene. Following transient middle cerebral artery occlusion (MCAO) in adult rats, expression of FosDT and Fos was induced. FosDT knockdown significantly ameliorated the postischemic motor deficits and reduced the infarct volume. Focal ischemia also increased FosDT binding to chromatin modifying proteins (CMPs) Sin3a and coREST (corepressors of the transcription factor REST). Furthermore, FosDT knockdown derepressed REST-downstream genes GRIA2, NFkappaB2, and GRIN1 in the postischemic brain. Thus, FosDT induction and its interactions with REST-associated CMPs, and the resulting regulation of REST downstream genes might modulate ischemic brain damage. LncRNAs, such as FosDT, can be therapeutically targeted to minimize poststroke brain damage. SIGNIFICANCE STATEMENT: Mammalian brain is abundantly enriched with long noncoding RNAs (LncRNAs). Functional roles of LncRNAs in normal and pathological states are not yet understood. This study identified that LncRNA FosDT induced after transient focal ischemia modulates poststroke behavioral deficits and brain damage. These effects of FosDT in part are due to its interactions with chromatin-modifying proteins Sin3a and coREST (corepressors of the transcription factor REST) and subsequent derepression of REST-downstream genes GRIA2, NFkappaB2, and GRIN1. Therefore, LncRNA-mediated epigenetic remodeling could determine stroke outcome. PMID- 26674870 TI - Unbiased, High-Throughput Electron Microscopy Analysis of Experience-Dependent Synaptic Changes in the Neocortex. AB - Neocortical circuits can be altered by sensory and motor experience, with experimental evidence supporting both anatomical and electrophysiological changes in synaptic properties. Previous studies have focused on changes in specific neurons or pathways-for example, the thalamocortical circuitry, layer 4-3 (L4-L3) synapses, or in the apical dendrites of L5 neurons- but a broad-scale analysis of experience-induced changes across the cortical column has been lacking. Without this comprehensive approach, a full understanding of how cortical circuits adapt during learning or altered sensory input will be impossible. Here we adapt an electron microscopy technique that selectively labels synapses, in combination with a machine-learning algorithm for semiautomated synapse detection, to perform an unbiased analysis of developmental and experience-dependent changes in synaptic properties across an entire cortical column in mice. Synapse density and length were compared across development and during whisker-evoked plasticity. Between postnatal days 14 and 18, synapse density significantly increases most in superficial layers, and synapse length increases in L3 and L5B. Removal of all but a single whisker row for 24 h led to an apparent increase in synapse density in L2 and a decrease in L6, and a significant increase in length in L3. Targeted electrophysiological analysis of changes in miniature EPSC and IPSC properties in L2 pyramidal neurons showed that mEPSC frequency nearly doubled in the whisker spared column, a difference that was highly significant. Together, this analysis shows that data-intensive analysis of column-wide changes in synapse properties can generate specific and testable hypotheses about experience-dependent changes in cortical organization. SIGNIFICANCE STATEMENT: Development and sensory experience can change synapse properties in the neocortex. Here we use a semiautomated analysis of electron microscopy images for an unbiased, column-wide analysis of synapse changes. This analysis reveals new loci for synaptic change that can be verified by targeted electrophysiological investigation. This method can be used as a platform for generating new hypotheses about synaptic changes across different brain areas and experimental conditions. PMID- 26674872 TI - Bidirectional Signaling of Neuregulin-2 Mediates Formation of GABAergic Synapses and Maturation of Glutamatergic Synapses in Newborn Granule Cells of Postnatal Hippocampus. AB - Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses. SIGNIFICANCE STATEMENT: The hippocampal dentate gyrus is one of special brain regions where neurogenesis persists throughout adulthood. Synaptogenesis is a critical step for newborn neurons to be integrated into preexisting neural network. Because neuregulin-2 (NRG2), a growth factor, is intensely expressed in these regions, we investigated whether it plays a role in synaptogenesis and dendritic growth. We found that NRG2 has dual roles in the development of newborn neurons. For GABAergic synaptogenesis, the extracellular domain of NRG2 acts as a ligand for a receptor on GABAergic neurons. In contrast, its intracellular domain was essential for dendritic outgrowth and glutamatergic synapse maturation. These results imply that NRG2 may play a critical role in network integration of newborn neurons. PMID- 26674871 TI - Selective VIP Receptor Agonists Facilitate Immune Transformation for Dopaminergic Neuroprotection in MPTP-Intoxicated Mice. AB - Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration used to model Parkinson's disease (PD). Survival of tyrosine hydroxylase neurons in the substantia nigra was determined by stereological tests after MPTP intoxication in mice pretreated with either VIPR1 or VIPR2 agonist or after adoptive transfer of splenic cell populations from agonist-treated mice administered to MPTP-intoxicated animals. Treatment with VIPR2 agonist or splenocytes from agonist-treated mice resulted in increased neuronal sparing. Immunohistochemical tests showed that agonist-treated mice displayed reductions in microglial responses, with the most pronounced effects in VIPR2 agonist-treated, MPTP-intoxicated mice. In parallel studies, we observed reductions in proinflammatory cytokine release that included IL-17A, IL-6, and IFN-gamma and increases in GM-CSF transcripts in CD4(+) T cells recovered from VIPR2 agonist-treated animals. Moreover, a phenotypic shift of effector to regulatory T cells was observed. These results support the use of VIPR2-selective agonists as neuroprotective agents for PD treatment. SIGNIFICANCE STATEMENT: Vasoactive intestinal peptide receptor 2 can elicit immune transformation in a model of Parkinson's disease (PD). Such immunomodulatory capabilities can lead to neuroprotection by attenuating microglial activation and by slowing degradation of neuronal cell bodies and termini in MPTP-intoxicated mice. The protective mechanism arises from altering a Th1/Th2 immune cytokine response into an anti inflammatory and neuronal sparing profile. These results are directly applicable for the development of novel PD therapies. PMID- 26674874 TI - miR-155-3p Drives the Development of Autoimmune Demyelination by Regulation of Heat Shock Protein 40. AB - microRNA-155 (miR-155) plays an important role in posttranscriptional gene regulation of the immune system. We and others have described miR-155 upregulation in T helper cells (Th) during the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We have shown that mice in which the miR-155 host gene (MIR155HG) has been deactivated are resistant to EAE. MIR155HG produces two different miRNA strands, miR-155-5p and miR-155-3p, and miR-155-5p has been considered the only functional miR-155 form. Surprisingly, we found that miR-155-3p is also strongly upregulated in Th cells infiltrating the brain in EAE. Functional manipulation of miR-155-3p expression revealed its particular role in regulation of Th17 development. The search for miRNA-155-3p target genes highlighted transcripts of two heat shock protein 40 genes, Dnaja2 and Dnajb1. These two genes negatively regulated Th17 differentiation, leading to decreased EAE. Therefore, our findings provide new insights into a previously unknown mechanism by which miR-155-3p controls Th17 cell differentiation and autoimmune demyelination. SIGNIFICANCE STATEMENT: Multiple sclerosis (MS) is brain-specific autoimmune disease mediated by T helper (Th) cells autoreactive to myelin. The mechanisms leading to MS are not fully understood and microRNAs (miRNAs) emerge as important regulators of the process. We report that, in an MS murine model of experimental autoimmune encephalomyelitis, miR-155 controls Th cell function by an unusual mechanism involving a rare form, miR-155-3p. miR-155-3p is specifically found in brain infiltrating myelin-autoreactive CD4(+) T cells and contributes to the development of an encephalitogenic Th17 population. miR-155-3p promotes Th17 by inhibiting two heat shock protein 40 genes, Dnaja2 and Dnajb1. Our findings indicate a unique miRNA function in the brain-infiltrating Th cells and suggest Dnaja2 and Dnajb1 as targets for intervention in autoimmune demyelination. PMID- 26674873 TI - Dopamine Modulates the Activity of Sensory Hair Cells. AB - The senses of hearing and balance are subject to modulation by efferent signaling, including the release of dopamine (DA). How DA influences the activity of the auditory and vestibular systems and its site of action are not well understood. Here we show that dopaminergic efferent fibers innervate the acousticolateralis epithelium of the zebrafish during development but do not directly form synapses with hair cells. However, a member of the D1-like receptor family, D1b, tightly localizes to ribbon synapses in inner ear and lateral-line hair cells. To assess modulation of hair-cell activity, we reversibly activated or inhibited D1-like receptors (D1Rs) in lateral-line hair cells. In extracellular recordings from hair cells, we observed that D1R agonist SKF-38393 increased microphonic potentials, whereas D1R antagonist SCH-23390 decreased microphonic potentials. Using ratiometric calcium imaging, we found that increased D1R activity resulted in larger calcium transients in hair cells. The increase of intracellular calcium requires Cav1.3a channels, as a Cav1 calcium channel antagonist, isradipine, blocked the increase in calcium transients elicited by the agonist SKF-38393. Collectively, our results suggest that DA is released in a paracrine fashion and acts at ribbon synapses, likely enhancing the activity of presynaptic Cav1.3a channels and thereby increasing neurotransmission. SIGNIFICANCE STATEMENT: The neurotransmitter dopamine acts in a paracrine fashion (diffusion over a short distance) in several tissues and bodily organs, influencing and regulating their activity. The cellular target and mechanism of the action of dopamine in mechanosensory organs, such as the inner ear and lateral-line organ, is not clearly understood. Here we demonstrate that dopamine receptors are present in sensory hair cells at synaptic sites that are required for signaling to the brain. When nearby neurons release dopamine, activation of the dopamine receptors increases the activity of these mechanosensitive cells. The mechanism of dopamine activation requires voltage gated calcium channels that are also present at hair-cell synapses. PMID- 26674875 TI - Causal Role of Motor Simulation in Turn-Taking Behavior. AB - Overlap between sensory and motor representations has been documented for a range of human actions, from grasping (Rizzolatti et al., 1996b) to playing a musical instrument (Novembre and Keller, 2014). Such overlap suggests that individuals use motor simulation to predict the outcome of observed actions (Wolpert, 1997). Here we investigate motor simulation as a basis of human communication. Using a musical turn-taking task, we show that pianists call on motor representations of their partner's part to predict when to come in for their own turn. Pianists played alternating solos with a videoed partner, and double-pulse transcranial magnetic stimulation was applied around the turn-switch to temporarily disrupt processing in two cortical regions implicated previously in different forms of motor simulation: (1) the dorsal premotor cortex (dPMC), associated with automatic motor resonance during passive observation of hand actions, especially when the actions are familiar (Lahav et al., 2007); and (2) the supplementary motor area (SMA), involved in active motor imagery, especially when the actions are familiar (Baumann et al., 2007). Stimulation of the right dPMC decreased the temporal accuracy of pianists' (right-hand) entries relative to sham when the partner's (left-hand) part had been rehearsed previously. This effect did not occur for dPMC stimulation without rehearsal or for SMA stimulation. These findings support the role of the dPMC in predicting the time course of observed actions via resonance-based motor simulation during turn-taking. Because turn taking spans multiple modes of human interaction, we suggest that simulation is a foundational mechanism underlying the temporal dynamics of joint action. SIGNIFICANCE STATEMENT: Even during passive observation, seeing or hearing somebody execute an action from within our repertoire activates motor cortices of our brain. But what is the functional relevance of such "motor simulation"? By combining a musical duet task with a real-time repetitive transcranial magnetic stimulation protocol, we provide evidence indicating that the dorsal premotor cortex plays a causal role in accurate turn-taking coordination between a pianist and their observed interaction partner. Given that turn-taking behavior is a fundamental feature of human communication, we suggest that simulation is a foundational mechanism underlying the temporal dynamics of communicative joint action. PMID- 26674876 TI - Neural Estimates of Imagined Outcomes in Basolateral Amygdala Depend on Orbitofrontal Cortex. AB - Reciprocal connections between the orbitofrontal cortex (OFC) and the basolateral nucleus of the amygdala (BLA) provide a critical circuit for guiding normal behavior when information about expected outcomes is required. Recently, we reported that outcome signaling by OFC neurons is also necessary for learning in the face of unexpected outcomes during a Pavlovian over-expectation task. Key to learning in this task is the ability to build on prior learning to infer or estimate an amount of reward never previously received. OFC was critical to this process. Notably, in parallel work, we found that BLA was not necessary for learning in this setting. This suggested a dissociation in which the BLA might be critical for acquiring information about the outcomes but not for subsequently using it to make novel predictions. Here we evaluated this hypothesis by recording single-unit activity from BLA in rats during the same Pavlovian over expectation task used previously. We found that spiking activity recorded in BLA in control rats did reflect novel outcome estimates derived from the integration of prior learning, however consistent with a model in which this process occurs in the OFC, these correlates were entirely abolished by ipsilateral OFC lesions. These data indicate that this information about these novel predictions is represented in the BLA, supported via direct or indirect input from the OFC, even though it does not appear to be necessary for learning. SIGNIFICANCE STATEMENT: The basolateral nucleus of the amygdala (BLA) and the orbitofrontal cortex (OFC) are involved in behavior that depends on knowledge of impending outcomes. Recently, we found that only the OFC was necessary for using such information for learning in a Pavlovian over-expectation task. The current experiment was designed to search for neural correlates of this process in the BLA and, if present, to ask whether they would still be dependent on OFC input. We found that although spiking activity in BLA in control rats did reflect the novel outcome estimates underlying learning, these correlates were entirely abolished by OFC lesions. PMID- 26674877 TI - Lin28B and Let-7 in the Control of Sympathetic Neurogenesis and Neuroblastoma Development. AB - The RNA binding protein Lin28B is expressed in developing tissues and sustains stem and progenitor cell identity as a negative regulator of the Let-7 family of microRNAs, which induces differentiation. Lin28B is activated in neuroblastoma (NB), a childhood tumor in sympathetic ganglia and adrenal medulla. Forced expression of Lin28B in embryonic mouse sympathoadrenal neuroblasts elicits postnatal NB formation. However, the normal function of Lin28B in the development of sympathetic neurons and chromaffin cells and the mechanisms involved in Lin28B induced tumor formation are unclear. Here, we demonstrate a mirror-image expression of Lin28B and Let-7a in developing chick sympathetic ganglia. Lin28B expression is not restricted to undifferentiated progenitor cells but, is observed in proliferating noradrenergic neuroblasts. Lin28 knockdown in cultured sympathetic neuroblasts decreases proliferation, whereas Let-7 inhibition increases the proportion of neuroblasts in the cell cycle. Lin28B overexpression enhances proliferation, but only during a short developmental period, and it does not reduce Let-7a. Effects of in vivo Lin28B overexpression were analyzed in the LSL-Lin28B(DBHiCre) mouse line. Sympathetic ganglion and adrenal medulla volume and the expression level of Let-7a were not altered, although Lin28B expression increased by 12- to 17-fold. In contrast, Let-7a expression was strongly reduced in LSL-Lin28B(DbhiCre) NB tumor tissue. These data demonstrate essential functions for endogenous Lin28 and Let-7 in neuroblast proliferation. However, Lin28B overexpression neither sustains neuroblast proliferation nor affects let-7 expression. Thus, in contrast to other pediatric tumors, Lin28B-induced NB is not due to expansion of proliferating embryonic neuroblasts, and Let-7-independent functions are implicated during initial NB development. SIGNIFICANCE STATEMENT: Lin28A/B proteins are highly expressed in early development and maintain progenitor cells by blocking the biogenesis and differentiation function of Let-7 microRNAs. Lin28B is aberrantly upregulated in the childhood tumor neuroblastoma (NB). NB develops in sympathetic ganglia and adrenal medulla and is elicited by forced Lin28B expression. We demonstrate that Lin28A/B and Let-7 are essential for sympathetic neuroblast proliferation during normal development. Unexpectedly, Lin28B upregulation in a mouse model does not affect neuroblast proliferation, ganglion size, and Let-7 expression during early postnatal development. Lin28B induced NB, in contrast to other pediatric cancers, does not evolve from neuroblasts that continue to divide and involves Let-7-independent functions during initial development. PMID- 26674878 TI - Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade. AB - Emerging evidence has indicated that the pathogenesis of neuropathic pain is mediated by spinal neural plasticity in the dorsal horn, which provides insight for analgesic therapy. Here, we report that the abundance of tumor necrosis factor receptor-associated factor 2 and NcK-interacting kinase (TNIK), a kinase that is presumed to regulate neural plasticity, was specifically enhanced in ipsilateral dorsal horn neurons after spinal nerve ligation (SNL; left L5 and L6). Spinal TNIK-associated allodynia is mediated by downstream TNIK-GluR1 coupling and the subsequent phosphorylation-dependent trafficking of GluR1 toward the plasma membrane in dorsal horn neurons. Tumor necrosis factor receptor associated factor 2 (TRAF2), which is regulated by spinal F-box protein 3 (Fbxo3) dependent F-box and leucine-rich repeat protein 2 (Fbxl2) ubiquitination, contributes to SNL-induced allodynia by modifying TNIK/GluR1 phosphorylation associated GluR1 trafficking. Although exhibiting no effect on Fbxo3/Fbxl2/TRAF2 signaling, focal knockdown of spinal TNIK expression prevented SNL-induced allodynia by attenuating TNIK/GluR1 phosphorylation-dependent subcellular GluR1 redistribution. In contrast, intrathecal administration of BC-1215 (N1,N2-Bis[[4 (2-pyridinyl)phenyl]methyl]-1,2-ethanediamine) (a novel Fbxo3 inhibitor) prevented SNL-induced Fbxl2 ubiquitination and subsequent TFAF2 de-ubiquitination to ameliorate behavioral allodynia via antagonizing TRAF2/TNIK/GluR1 signaling. By targeting spinal Fbxo3-dependent Fbxl2 ubiquitination and the subsequent TRAF2/TNIK/GluR1 cascade, spinal application of a TNF-alpha-neutralizing antibody ameliorated SNL-induced allodynia, and, conversely, intrathecal TNF-alpha injection into naive rats induced allodynia via a spinal Fbxo3/Fbxl2-dependent modification of the TRAF2/TNIK/GluR1 cascade. Together, our results suggest that spinal TNF-alpha contributes to the development of neuropathic pain by upregulating TRAF2/TNIK/GluR1 signaling via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic pain by targeting the F-box protein or TNIK. SIGNIFICANCE STATEMENT: TNF-alpha participates in neuropathic pain development by facilitating the spinal TRAF2-dependent TNIK-GluR1 association, which drives GluR1-containing AMPA receptor trafficking toward the plasma membrane. In addition, F-box protein 3 modifies this pathway by inhibiting F-box and leucine-rich repeat protein 2 mediated TRAF2 ubiquitination, suggesting that protein ubiquitination contributes crucially to the development of neuropathic pain. These results provide a novel therapeutic strategy for pain relief. PMID- 26674879 TI - Comparison of Penetration of Irrigant Activated by Traditional Methods with A Novel Technique. AB - INTRODUCTION: The effectiveness of irrigation depends upon various irrigation activation methods & devices used. AIM: To compare and evaluate the penetration of irrigant upto working length and into simulated lateral canals using four different irrigation activation techniques. MATERIALS AND METHODS: The root canals of 60 single-rooted teeth were instrumented using the proTaper rotary system. After decalcification of each sample tooth, three simulated lateral canals were created at 2mm, 4mm and 6mm levels from the root apex using a 06-size C+ file. After clearing the samples they were randomly assigned into four experimental groups (n=15) and 1ml of Irrigating Contrast Solution (ICS) was delivered into all samples and then it is activated with 4 different methods Group I-Conventional syringe and needle, Group II - Sonic activation with Endo activator, Group III - Ultrasonic activation with ultrasonic tips and Group IV - Activation using reciprocation movement. All the samples were examined under a stereomicroscope and irrigant penetration was evaluated by means of penetration of ICS. RESULTS: Group III and Group IV resulted in better penetration of ICS into lateral canals at 2mm and 4mm depth (p<0.001), when compared with Group I and II. At lateral canals 6mm all the groups except Group I, had shown 100 % penetration. CONCLUSION: The activation of irrigant using reciprocation was able to achieve penetration of irrigating contrast solution both up to the working length and into lateral canals. Hence the clinical significance of this method of irrigant activation is that it can be used for effective penetration of irrigants both upto working length and into lateral canals. PMID- 26674880 TI - Viral load is associated with abnormal serum levels of micronutrients and glutathione and glutathione-dependent enzymes in genotype 3 HCV patients. AB - BACKGROUND: Oxidative stress in hepatitis C patients has been linked to hepatitis C virus. We verified this assumption in HCV genotype 3 patients by detecting the relationship between viral load and certain specific oxidative stress markers like Cu, Mn, Fe, Se, Zn and glutathione and glutathione-dependent enzymes. METHOD: Subjects (n = 200, average age 24 years) with quantitative HCV RNA polymerase chain reaction-proven genotype 3 hepatitis C were simultaneously evaluated. Cu, Mn, Fe, Se and Zn serum levels were by using atomic absorption spectrophotometer. Internationally accepted methods were used for viral load quantification of glutathione, GR and Gpx serum levels. RESULT: There was a significant correlation between HCV viral load and studied parameters. With the increase of viral load from mild group (200,000-1,000,000 copies/ml) to severe group (5,000,000-25,000,000 copies/ml) the serum levels of Cu, Mn, Zn, and Fe and glutathione reductase were found to be abnormally high. However, in severe viral load group serum concentration of Se and glutathione was less than the healthy controls. CONCLUSION: As a significant correlation was detected between the study parameters in genotype 3 HCV patients, it is concluded that the studied micronutrients and glutathione and glutathione-dependent enzymes are the biomolecular targets of HCV to induce oxidative stress. GENERAL SIGNIFICANCE: Constant monitoring and regulation of the recommended biomolecular targets of HCV can improve the plight of more than 170 million patients suffering from hepatitis C virus around the globe. PMID- 26674881 TI - Gut Microbiota and Colorectal Cancer. AB - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide whose incidence has increased rapidly in recent years. There is growing evidence that the complex gut microbiota community plays an important role in the development of intestinal tumorigenesis. SUMMARY: This review aimed to explore the correlation between gut microbiota and CRC as well as to identify the pathogens and their metabolites that affect CRC and the potential models of gut microbiota action. It promotes our understanding of the correlation between gut microbiota and CRC. KEY MESSAGE: Our knowledge of the risk factors associated with gut microbiota for CRC development, as well as of the mechanism how intestinal bacteria act on colorectal tumorigenesis, has improved, leading to a better understanding of the correlation between gut microbiota and CRC. PRACTICAL IMPLICATIONS: The intestinal microbiota community has a close relationship with CRC by influencing the mechanism of the body and by regulating the physiological function of the colorectum and even the entire digestive system. Gut microbiota have been linked to CRC based upon their toxic and genotoxic metabolites production by fermentation of dietary ingredients. These metabolites could bind specific intestinal cell surface receptors and subsequently affect intracellular signal transduction. The mechanisms by which gut microbiota affect CRC development include the 'Alpha-bug' model, the 'driver-passenger' model and the 'intestinal microbiota adaptions' model. This review promotes our understanding of the correlation between gut microbiota and CRC. PMID- 26674882 TI - Incidence and Severity of Foot and Ankle Injuries in Men's Collegiate American Football. AB - BACKGROUND: American football is an extremely physical game with a much higher risk of injury than other sports. While many studies have reported the rate of injury for particular body regions or for individual injuries, very little information exists that compares the incidence or severity of particular injuries within a body region. Such information is critical for prioritizing preventative interventions. PURPOSE: To retrospectively analyze epidemiological data to identify the most common and most severe foot and ankle injuries in collegiate men's football. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury data were obtained from the National Collegiate Athletic Association (NCAA) Injury Surveillance System (ISS) for all foot and ankle injuries during the 2004 2005 to 2008-2009 seasons. Injuries were analyzed in terms of incidence and using multiple measures of severity (time loss, surgeries, medical disqualifications). This frequency and severity information is summarized in tabular form as well as in a 4 * 4 quantitative injury risk assessment matrix (QIRAM). RESULTS: The rate of foot and ankle injuries was 15 per 10,000 athletic exposures (AEs). Five injuries were found to be responsible for more than 80% of all foot and ankle injuries: lateral ankle ligament sprains, syndesmotic (high ankle) sprains, medial ankle ligament sprains, midfoot injuries, and first metatarsophalangeal joint injuries. Ankle dislocations were found to be the most severe in terms of median time loss (100 days), percentage of surgeries (83%), and percentage of medical disqualifications (94%), followed by metatarsal fractures (38 days, 36%, and 49%, respectively) and malleolus fractures (33 days, 41%, and 59%, respectively). Statistical analysis suggests that the 3 measures of severity are highly correlated (r > 0.94), thereby justifying the use of time loss as a suitable proxy for injury severity in the construction of the QIRAM. CONCLUSION: Based on the QIRAM analysis, the 5 highest risk injuries were identified based on both incidence and severity (ankle dislocations, syndesmotic sprains, lateral ankle ligament sprains, metatarsal fractures, and malleolus fractures). A better understanding of the relative incidence and severity of these injuries will allow coaches, trainers, and researchers to more effectively focus their preventative interventions. PMID- 26674883 TI - Eosinophilic Angiocentric Fibrosis of Sinonasal Region: A Rare & Under Reported Entity. AB - Eosinophilic angiocentric fibrosis is a rare pathology of the sinonasal tract and the upper respiratory system characterised by fibrosis with poorly understood pathogenesis. A 47-year-old male presented with a swelling over the dorsum of the nose. The possibility of fungal granuloma was being suggested on Magnetic Resonance Imaging (MRI). Histopathology showed thick collagen bundles whorling around vessels giving an onion skin appearance with focal area of vasculitis. An inflammatory reaction rich in eosinophils along with a fibrotic stroma was seen which was highly characteristic of eosinophilic angiocentric fibrosis. Clinically & microscopically it mimics Granuloma faciale, Wegener's Granulomatosis, Churg Strauss Syndrome, Kimura's disease and few other granulomatous conditions thus making diagnosis difficult. A probable allergic origin is being suggested because of the typical eosinophil-rich inflammatory reaction. Finally the diagnosis of Eosinophilic Angiocentric Fibrosis was given. It is a diagnosis of exclusion having characteristic histomorphological findings thus biopsy is always required to distinguish it from other lesions whose treatment differs. PMID- 26674884 TI - Asenapine for bipolar disorder. AB - Asenapine (Saphris((r))) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD. PMID- 26674885 TI - Analysis of Lid Contour in Thyroid Eye Disease With Upper and Lower Eyelid Retraction Using Multiple Radial Midpupil Lid Distances. AB - PURPOSE: The aim of this study was to analyze upper and lower eyelid contours in adult patients with thyroid eye disease (TED) and normal adults using a software program that measures multiple radial midpupil lid distance (MPLD). METHODS: Analysis targeted 61 eyes from 61 normal adults who had never undergone eyelid surgery or ophthalmic surgery and 63 eyes from 63 patients with TED. Digital pictures of primary gaze were analyzed using custom software. Conventional MPLD (90 degrees , 270 degrees ) and 12 oblique MPLDs were collected every 15 degrees across the temporal (105 degrees , 120 degrees , 135 degrees , 150 degrees , 165 degrees , 180 degrees ) and nasal (75 degrees , 60 degrees , 45 degrees , 30 degrees , 15 degrees , 0 degrees ) sectors of the upper eyelid. For lower eyelid contours, 9 oblique MLPDs in the temporal sector (255 degrees , 240 degrees , 225 degrees , 210 degrees , 195 degrees ) and nasal sector (285 degrees , 300 degrees , 315 degrees , 330 degrees ) of the lower eyelid were analyzed. RESULTS: From all angles, the MPLD of patients with TED was larger than that of the control group. The mean difference between the 2 groups was larger for the upper eyelid (0 degrees ~ 180 degrees ) than the lower eyelid (195 degrees ~ 330 degrees ). When comparing symmetry by dividing into each angle, the ratio of 90 degrees /270 degrees (MRD1/MRD2) demonstrated greater in patients with TED (P = 0.000). Temporal/nasal eyelid contour symmetry in the upper eyelid, investigated using the distance ratio of the nasal sector/temporal sector (15 degrees /165 degrees , 30 degrees /150 degrees , 45 degrees /135 degrees , 60 degrees /120 degrees , 75 degrees /105 degrees ), was significantly smaller in patients with TED (P < 0.05). However, there was no significant difference between the 2 groups regarding temporal/nasal eyelid contour symmetry of the lower eyelid (330 degrees /210 degrees , 315 degrees /225 degrees , 300 degrees /240 degrees , 285 degrees /255 degrees ). CONCLUSIONS: Radial MPLD is effective for analyzing eyelid contour. In our study, lateral flare of upper lid retraction and flat appearance of lower lid retraction were distinct characteristics in patients with TED. Consideration of eyelid contour in patients with TED may improve corrective surgery for eyelid retraction. PMID- 26674886 TI - Patient-Specific Orbital Implants: Development and Implementation of Technology for More Accurate Orbital Reconstruction. AB - Fracture of the orbital floor is commonly seen in facial trauma. Accurate anatomical reconstruction of the orbital floor contour is challenging. The authors demonstrate a novel method to more precisely reconstruct the orbital floor on a 50-year-old female who sustained an orbital floor fracture following a fall. Results of the reconstruction show excellent reapproximation of the native orbital floor contour and complete resolution of her enopthalmos and facial asymmetry. PMID- 26674887 TI - A Cadaveric Study of the Communication Patterns Between the Buccal Trunks of the Facial Nerve and the Infraorbital Nerve in the Midface. AB - Most nerve communications reported in the literature were found between the terminal branches. This study aimed to clarify and classify patterns of proximal communications between the buccal branches (BN) of the facial nerve and the infraorbital nerve (ION).The superficial musculoaponeurotic system protects any communication sites from conventional dissections. Based on this limitation, the soft tissues of each face were peeled off the facial skull and the facial turn down flap specimens were dissected from the periosteal view. Dissection was performed in 40 hemifaces to classify the communications in the sublevator space. Communication site was measured from the ala of nose.A double communication was the most common type found in 62.5% of hemifaces. Triple and single communications existed in 25% and 10% of 40 hemiface specimens, respectively. One hemiface had no communication. The most common type of communication occurred between the lower trunk of the BN of the facial nerve and the lateral labial (fourth) branch of the ION (70% in 40 hemifaces). Communication site was deep to the levator labii superioris muscle at 16.2 mm from the nasal ala. Communications between the motor and the sensory nerves in the midface may be important to increase nerve endurance and to compensate functional loss from injury.Proximal communications between the main trunks of the facial nerve and the ION in the midface exist in every face. This implies some specific functions in normal individuals. Awareness of these nerves is essential in surgical procedure in the midface. PMID- 26674888 TI - Evaluation of Interforaminal Mandible Region of Individuals With Pierre Robin Sequence and Treacher Collins Syndrome Through the Cone-Beam Computed Tomography. AB - The Pierre Robin sequence (PRS) and the Treacher Collins syndrome (TCS) are conditions that cause significant abnormalities of jaw. This study was conducted in anticipation of evaluating the morphology of interforaminal region and identify the anatomic variations: anterior loop and mandibular incisive canal, in individuals with PRS and TCS by cone-beam computed tomography and compare them with individuals without craniofacial anomalies. By applying the t-test, the results showed no statistically significant difference, allowing to infer that there are no significant differences in interforaminal mandible morphology between groups and indicated that the prevalence and location of the studied anatomic variations are consistent with those described in literature. PMID- 26674889 TI - Stress Over Implants of One-Piece Cast Frameworks Made With Different Materials. AB - This study aims to compare stress transmitted to implants and passive fit of one piece cast frameworks fabricated with 3 different materials: commercially pure titanium (G1-CP Ti), cobalt-chromium alloy (G2-Co-Cr), and nickel-chromium titanium alloy (G3-Ni-Cr-Ti). In total, 12 frameworks simulating bars for fixed prosthesis in a model with 5 implants were fabricated. The passive fit of the framework interface was measured using an optical microscope and the stresses transmitted to implants were measured using quantitative photoelastic analysis. Data were statistically analyzed by analysis of variance (ANOVA) and least significant difference (LSD) tests (alpha = 0.05). Mean and standard deviation values of passive fit and stress over implants are presented, respectively: G1 [472.49 (109.88) MUm and 11.38 (9.23) KPa], G2 [584.84 (120.20) MUm and 15.83 (9.30) KPa], and G3 [462.70 (179.18) MUm and 16.39 (9.51) KPa]. For stress over implants, there were significant differences between G1, G2, and G3 (P = 0.035), being the lowest values for the G1. There were no significant differences for passive fit between G1 and G3 (P = 0.844), but both were statistically different from G2 (P = 0.028 and P = 0.035, respectively), which showed the worse results. It may be concluded that the stress over implants was affected by the tested materials. The CP Ti presented the best values for the evaluated items. PMID- 26674890 TI - The Effect of Selenium on Ischemia-Reperfusion Injury: An Experimental Study on a Transverse Rectus Abdominis Musculocutaneous Flap Model. AB - BACKGROUND: The aim of this study is to investigate effects of selenium and enlighten the possible mechanism of action in a rat transverse musculocutaneous flap model following ischemia-reperfusion injury. MATERIALS AND METHODS: In this study, an experimental model, which mimicked free tissue transfer, was applied. Twenty-four male Wistar Albino rats were divided into a control group (N = 12), and a selenium treated group (N = 12). A superiorly based transverse rectus abdominis musculocutaneous (TRAM) flap was elevated and an ischemic insult for 4 hours was given. In selenium treated group (Group 2), sodium selenite (0.625 mg/kg) was injected intraperitoneally (i.p), 2 hours before the induction of ischemia. Six rats from each group were sacrificed at 24 hours after the operation and malonyldialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels were measured biochemically, whereas the intensity of neutrophil infiltration was evaluated. For the rest of the rats in Group 2, sodium selenite was injected at the same dose everyday to the postoperative 10th day, in which the remaining 6 rats from each group were sacrificed. On postoperative 10th day, flap viability was assessed along with the evaluation of intensity of neovascularization. RESULTS: In Group 1, MDA levels were higher significantly (P < 0.05) when compared with Group 2. No statistical difference, however, was found for NO (P > 0.05), and GSH (P > 0.05) levels among Group 1 and 2. Neutrophil infiltration was more intense in Group 1, when compared with Group 2 whereas neovascularization was more abundant in samples of Group 2. Group 2 shows higher average flap surface areas when compared with Group 1 (P < 0.05). DISCUSSION: The results of this study demonstrated the preventive effect of selenium against ischemia-reperfusion injury by reducing tissue necrosis in muscle flaps possibly by decreasing MDA, increasing neovascularization, and decreasing neutrophil infiltration, thus suppressing inflammation. PMID- 26674891 TI - Pediatric Facial Fractures. AB - INTRODUCTION: There are few published articles describing the epidemiology of facial fractures in South Africa, and there is only one published study in pediatric patients. MATERIAL AND METHODS: This study retrospectively reviewed all medical records in a major metropolitan pediatric hospital in Cape Town, South Africa from September 2006 through May 2014. Inclusion criteria were children aged under the age of 13 with facial fractures. Fractures were assessed through head computed tomography (CT) scans. Patient's age, sex, cause of injury, general condition, existence of concomitant injuries, location of fractures, type of interventions, and length of stay were recorded and analyzed. RESULTS: A total of 53 men and 34 women were included in the study. Motor vehicle collisions (MVC) were the most common cause of facial fractures (56.3%). One hundred thirty facial fractures were presented on CT scans. The most common fractures in this study were mandible (43.1%). Comparing unrestrained motor vehicle collisions (UMVC) patients with those of other etiologies (OE), there was an increase in the average number of fractures (OE: 1.1, UMVC: 1.9; P < 0.0001), the average length of stay (OE: 4 days, UMVC: 9 days; P < 0.003), and the probabilities of sustaining concomitant injuries (OE: 31.0%, UMVC: 68.8%; P < 0.05) and requiring an operation (OE: 42.3%, UMVC: 81.3%; P < 0.01). DISCUSSION: This study establishes MVC as the most common etiology of facial fractures in South Africa. It demonstrates an increase in the complexity of facial injuries in unrestrained MVCs, suggesting the need for public awareness campaigns to install restraint devices in automobiles in South Africa. PMID- 26674892 TI - Treatment for Infantile Hemangiomas: Selection Criteria, Safety, and Outcomes Using Oral Propranolol During the Early Phase of Propranolol Use for Hemangiomas. AB - OBJECTIVE: Despite the increasing popularity of propranolol for treatment of infantile hemangioma (IH), there is need for further evidence of efficacy and safety. This study is a retrospective review of one institution's experience treating IH with propranolol using a standard protocol. METHODS: Between 2009 and 2014, patients with IH were evaluated for treatment with propranolol. Exclusion criteria included a history of hypoglycemia, respiratory disorders, and cardiovascular disorders. Propranolol, 2 mg/kg/d, was initiated during 48-hour inpatient stay. Weight and complications were monitored. Appearance was assessed by Visual Analog Cosmetic Scale (VACS) via serial photography. RESULTS: Twenty three patients were treated with propranolol. Average age at initiation of therapy was 14.9 weeks. Twenty-two lesions were on the head and neck, and 1 was on the trunk. Average treatment duration was 54.3 weeks (range 24-148 wk). Treatment was confirmed to be complete in 23 patients at the time of review (91.3%). Two patients were lost to follow-up. Posttreatment color, size, and VACS improved significantly (P < 0.05). There was no significant difference between first and most recent weight. Two patients experienced hypoglycemia, 1 during a diarrheal illness and 1 during inpatient treatment initiation. CONCLUSION: The authors present a series of patients with IH safely treated with 2 mg/kg/d of propranolol. Using a strict protocol, few complications were observed. Patients achieved significant reduction in size and improvement of the overall appearance of IH. PMID- 26674893 TI - Le Fort II Setback Osteotomy to Correct Naso-Ethmoido-Maxillary Protrusion. AB - BACKGROUND: Marked class II dentofacial deformity associated with centrofacial protrusion may be difficult to treat successfully. The purpose of this article was to report on Le Fort II setback osteotomy (LIISBO) to correct Naso-Ethmoido Maxillary Protrusion (NEMP), to describe its indications and surgical techniques, and to analyze aesthetic and occlusal changes. MATERIALS AND METHODS: From November 2011 to November 2014, patients with NEMP, treated with LIISBO, were included in the study. Cephalometric analysis of Delaire was performed before and 1 year after surgery. Skeletal and soft tissues movements were measured between preoperative and postoperative lateral cephalographs. RESULTS: Fourteen patients were treated in our department by LIISBO. Ten patients were analyzed and presented a stable class I occlusion with reliable aesthetic results. The mean maxillary setback was -2.8 mm at nasopalatal point (Np), -3.1 mm at A point, and 3.7 mm at Pti (inferior pterygomaxilar point). The mean maxillary impaction was 2.4 mm at Np, -3 mm at A point, and -0.6 mm at Pti. The B, mental, and pogonion points showed an advancement with an average of +7.4, +7.9, and +7.7 mm, respectively. Measured soft tissues variations showed a backward movement of the nasal tip, the subnasal point, and the upper lip of -1.5, -1.6, and -0.7 mm, respectively. The lower lip, sublabial point, and the skin pogonion were advanced by +3.2, +5.4, and +6.2 mm, respectively. CONCLUSIONS: Le Fort II setback osteotomy may be regarded as the ideal treatment for adult patient presenting a NEMP syndrome. PMID- 26674894 TI - Design, Manufacturing, and In Vitro Testing of a Patient-Specific Shape-Memory Expander for Nose Reconstruction With Forehead Flap Technique. AB - Forehead skin is widely acknowledged as a good donor site for total nasal reconstruction, thanks to its matching color, texture, and abundant vascularity. The forehead flap technique uses an axial pattern flap forehead skin to replace missing nasal tissue. To increase the amount of available tissue and reduce the size of the tissue defect after flap mobilization, tissue expanders may be used. Although this is a relatively established technique, limitations include reduced moldability of the forehead skin (which is thicker than the nasal skin), and the need for multiple sessions of expansion to achieve a sufficient yield to close the forehead.Shape-memory metals, such as nitinol, can be programmed to "remember" complex shapes. In this work, the methodology for producing a prototype of nitinol tissue expander able to mold the skin in a predetermined patient-specific skin shape is described. A realistic nose mold was manufactured using metal rapid prototyping; nitinol sheet and mesh were molded into nose-shape constructs, having hyperelastic as well as shape-memory capability. Computed tomography scanning was performed to assess the ability of the structure to regain its shape after phase transformation upon cooling within 2% of initial dimensions. The prototypes were implanted in a pig forehead to test its ability to impose a nose shape to the forehead skin.The shape-memory properties of nitinol offer the possibility of producing bespoke tissue expanders able to deliver complex, precisely designed skin envelopes. The hyperelastic properties of nitinol allow constant preprogrammed expansion forces to be generated throughout the expansion process. PMID- 26674895 TI - Orbicularis Oculi Myocutaneous Flap for Upper Cicatricial Ectropion. AB - The correction of cicatricial ectropion often presents a challenge to plastic surgeons because of the difficulty obtaining tissue of similar color and texture and producing minor morbidity to donor sites. The authors present the correction of upper cicatricial ectropion by rotating the orbicularis myocutaneous flap from the same lid. From April 2008 to March 2014, 8 consecutive patients with upper cicatricial ectropion underwent transfer of orbicularis oculi myocutaneous flap. The main outcome measures included the complications, recurrence, and cosmesis. All flaps were viable with partial recurrence observed in 1 severe case. Satisfactory function and cosmesis were obtained in the evaluation of the patients during the follow-up period with a 4- to 41-month range. The redundant flap which should be excised during the blepharoplasty can be used to correct upper cicatricial ectropion. Good results can be obtained because of the well hidden incision scar and minor donor-site morbidity. PMID- 26674896 TI - Reconstruction of the Auricular Defect After Excision of Verrucous Carcinoma. AB - Verrucous carcinoma is a highly differentiated variant of squamous cell carcinoma with a high local recurrence rate. Few studies of primary verrucous carcinoma of the auricle have reported on the surgical outcome. The authors present herein a case in which a verrucous carcinoma of the auricle was successfully removed and reconstructed using a retroauricular pull-through island flap, and the authors briefly review the relevant literature. PMID- 26674897 TI - Temporalis Muscle Transfer for the Treatment of Lagophthalmos in Patients With Leprosy: Refinement in Surgical Techniques to Prevent Postoperative Ptosis. AB - Facial paralysis resulting from leprosy has a serious impact on the entire face especially in the areas innervated by the facial nerves. In particular, lagophthalmos in patients with leprosy causes exposure keratitis, corneal, and conjunctival dryness, which can progress to blindness and disfigurement. Recently, we conducted 4 different temporalis muscle transfer (TMT) methods over the last 4 years to reduce ptosis. The methods used included Brown-McDowell, McCord-Codner, modified Gillies-Anderson, and modified Gillies. Seventy-five TMT operations in 60 patients were performed between 2011 and 2014. The mean age was 70.1. Fifteen patients had bilateral TMT procedures. As a result, ptosis appeared in 14(18.7%) of 75 TMT procedures for 4 years. To prevent or correct this complication, the following 4 technical refinements have simplified the surgery and yield better surgical outcomes. First, an increase in the length of the temporalis muscle flap to approximately 8 cm with a parallel course to the lateral canthus will reduce oblique pull. Second, the width of the fascia sling in the upper eyelid is narrowed (3-4 mm) to reduce weight on the eyelid. Third, the fascia sling in the upper lid should not be located along the full length of the upper lid but terminate 3.5 cm medial to lateral canthal tendon and in other words, should not be tied at the medial canthal tendon to reduce tension and weight. Lastly, the fascia sling in the eyelid should be located shallow (probably in subdermal layer) and as near as possible to the lid margin to prevent any functional disturbance in levator aponeurosis. PMID- 26674898 TI - The Efficacy of Preoperative Oral Tranexamic Acid on Intraoperative Bleeding During Rhinoplasty. AB - BACKGROUND: Perioperative bleeding is a common side effect of rhinoplasty which may impose the blood transfusion to the patients. As a result of risks and cost of blood transfusion, this study is planned to reduce blood loss in these surgeries. Since tranexamic acid (TXA) has been reported to reduce bleeding and subsequent possible need for blood transfusion, the purpose of this study was to evaluate the efficacy of oral TXA on blood loss during rhinoplasty. METHODS AND MATERIALS: In this double-blind, randomized, placebo-controlled clinical trial, 50 participants underwent rhinoplastic surgery. These participants were divided into 2 groups; 25 were randomly assigned to each 1. The patients in the first group received 1 g (2 * 500 mg) tranexamic acid tablets, and the patients in the second group received placebo 2 hours before starting the surgery. All patients were operated by the same surgical team and the same anesthetic techniques were used during the surgery. Gender, age, BMI, duration of operation, the amount of blood loss, and surgeon's satisfaction rate were the variables studied. RESULTS: The first group (TXA group) consisted of 11 males (44%) and 14 females (56%) and the second group consisted of 13 males (52%) and 12 females (48%). There was no statistical difference in the distribution of the variables between the 2 groups, except for the blood loss, duration of operation, and surgeon's satisfaction. The mean total blood loss was 144.6 +/- 60.28 mL in "group 1" and 199.6 +/- 73.05 mL in "group 2" (P < 0.05). Duration of operation in the first group was less than the second group (2.60 +/- 0.53 hours vs. 2.99 +/- 0.59 hours) (P = 0.017). The surgeon was more satisfied with the quality of surgical field and visualization in "group 1" (3.76 +/- 0.72) than "group 2" (2.16 +/- 0.50) (P = 0.001). CONCLUSION: The preoperative administration of 1 g oral tranexamic acid significantly decreased the blood loss in patients undergoing rhinoplastic surgery without any significant adverse effects.Iranian registry no:IRCT201312271674N10 (www.irct.ir). PMID- 26674899 TI - Endoscopic Browlift in the Receding Hairline Patient. AB - The upper third of the face, composed of the forehead and the brow, is a critical aesthetic subunit. Brow ptosis is a common presenting complaint for patients seeking elective improvement of their facial appearance. Browlift surgery has a long history of technique evolution, with various reported methods and refinements. Since the introduction of the endoscopic brow lifting in the 1990s, it has become widely accepted as an approach to forehead rejuvenation. Endoscopy provides minimal incisions in well hidden areas, avoiding long, visible scars. A great number of patients who seek forehead rejuvenation already have a receding hairline. The patient with a receding hairline has been viewed as an unfavorable candidate for the endoscopic browlift approach. This report describes the case of a 67-year-old man with a receding hairline that was referred for brow ptosis and upper eyelid dermatochalasis. An upper eyelid blepharoplasty and an endoscopic browlift were performed. Incisions were placed in the temporal region bilaterally, as well as a single central incision placed in the anterior hairline. Two small horizontal incisions were placed in forehead crease lines for placement of the anchoring pins. This technique allowed for ease of dissection and resulted in inconspicuous scars. There was no elevation of the hairline; the brow was examined to be at a normal position at the level of the supraorbital rim at 12 months postoperative. The patient was highly satisfied with the operative outcome. LEVEL OF EVIDENCE: V. PMID- 26674900 TI - Quantitative Mandibular Angle Ostectomy Facilitated by Oscillating-Blade Saw With Scalable Guide. AB - BACKGROUND: Although various techniques of mandibular angle ostectomy have been devised to correct overly prominent bony contours, none have incorporated methods to delineate the surgical line with precision. Herein, the authors describe one means of marking an ostectomy line more easily, using a specially designed oscillating-blade saw. METHODS: Between July 2013 and June 2014, a total of 75 patients underwent quantitative mandibular angle ostectomy using a custom oscillating-blade saw equipped with a scalable guide. Corticectomy, also done routinely to improve frontal appearance, called for a reciprocating saw only. Aesthetic outcomes gauged subjectively by the questionnaire about satisfaction and symmetry after postoperative 6 months. RESULTS: Satisfaction score was 4.9 and symmetric score was 4.7. No major complications, such as persistent nerve injury or fracture, were encountered. CONCLUSIONS: Use of an oscillating-blade saw equipped with a scalable guide facilitated quantitative mandibular angle ostectomy, enabling precise, and reproducible surgery with satisfactory outcomes with less complications. PMID- 26674901 TI - Mandibular Reconstruction in a Patient With Rosai-Dorfman Disease. AB - OBJECTIVE: The Rosai-Dorfman disease (RDD) is a rare disorder known as sinus histiocytosis with massive lymphadenopathy which affects other organs besides the lymphatic nodes. The most frequent clinical presentation is the skin involvement, but the most serious one is when the central nervous system is compromised. There are not clinical cases in the literature reporting the mandibular involvement and its management. The aim of this study is to report the case of a patient with this disease, her treatment, and her follow-up. STUDY: A 32-year-old woman with RDD, who underwent a right mandibulectomy to treat osteomyelitis, and who suffered hemolytic anemia, lymphoproliferative syndrome, and bacterial meningitis by meningococcus treated successfully, is presented. She also had osteosynthesis plate exposure in 3 occasions. The authors performed a mandibular reconstruction with a fibula free flap. Vertical osteogenic distraction was done to improve the vertical height of the bone for osteointegrated implants and later oral rehabilitation. METHODS: The senior authors performed mandibular reconstruction with a fibula free flap. Vertical osteogenic distraction was performed to improve the vertical height of the bone for osteointegrated implants and later oral rehabilitation. The patient achieved adequate function with a good mandibular height and occlusion. RESULTS: The patient had a follow-up of 6 months. She is highly satisfied with her result. Preoperative and postoperative photos are shown. DISCUSSION: In this rare case, the authors show the difficulties when treating this disease. The follow-up of the patient showed a successful reconstruction with good functional results. PMID- 26674902 TI - The Role of Resorbable Mesh as a Fixation Device in Craniosynostosis. AB - The purpose of the study was to present our experience with endocranial fixation using the Resorb-X mesh (KLS Martin, Jacksonville, FL) in frontoorbital reconstruction. A retrospective review of all patients underwent frontoorbital advancement at our institution from 2003 to 2012 was performed. Inclusion criterion included: pediatric patients who underwent frontoorbital advancement for craniosynostosis; patients underwent treatment of the craniosynostosis only at our center; resorbable fixation devises were applied only endocranially; and follow-up was >= 2 years. Patients' evaluation included demographic information, postoperative complications, surgical outcomes, and postoperative computed tomographic imaging if accessible. Thirty-nine patients met the inclusion criteria. Resorbable plates were used in 16 patients and Resorb-X mesh in 23 patients. Observed complications were unrelated to the fixation system used. Resorption of fixation devices was evident in all patients after 20 months following reconstruction. There were no incidents of local reaction to the fixation system. Frontoorbital area contour was deemed good in 24 patients and excellent in 15 patients by both families and attending surgeon. There was a statistical significant difference (P = 0.030) between patients <= 12 months and >12 months regarding the complications rate. Endocranial fixation using the Resorb-X mesh is easily applicable, avoids material palpability, and provides stable and secure fixation. This technique is superior to the conventional endocranial osseous fixation with absorbable plates, as it avoids some of its possible complications while providing all the benefits of resorbable fixation. PMID- 26674903 TI - The Efficacy of Continuous Negative Pressure and Irrigation Treatment Inside the Wound by a Closed System in Reconstruction of All Layers of the Cranium Accompanying Infection and Cerebrospinal Fluid Leakage. AB - There have been many reports to date with respect to treatments on reconstruction of the cranium without accompanying infections following trauma and tumor resection. The morality is, however, high in patients observed with generation of cranial bone defect of all layers accompanying infection and cerebrospinal fluid leakage, and moreover, there are barely any reports on such cases because of the reconstruction thereof being very difficult. In this study, the authors were able to cure such 2 cases by carrying out continuous negative pressure and irrigation treatment inside the wound by a closed system following transplant of free latissimus dorsi muscle flap. This method is believed to be very effective for cranial bone defect of all layers accompanying infection and cerebrospinal fluid leakage, in which treatment was determined to be very difficult. PMID- 26674904 TI - Delayed Superior Orbital Fissure Syndrome After Reconstruction of Blowout Fracture. AB - The superior orbital fissure syndrome (SOFS) has been known to be a condition caused by impairment of the nerves that cross the superior orbital fissure. Traumatic SOFS is an uncommon complication which occurs usually within 48 hours after a facial injury. A 25-year-old male sustained facial trauma following an altercation. Clinical findings on presentation included swelling, ecchymosis, hyphema, subretinal hemorrhage, and mild extraocular movement limitation upon lateral gaze on his right eyelids. Facial computed tomography scan confirmed fractures of the medial walls of the right orbit and herniation of orbital soft tissue without the incarceration of medial rectus muscle. Ten days after the trauma, the operation was performed. On postoperative day 16, the patient showed ptosis of the right upper eyelid with a fixed pupil, and there was a hypoesthesia over the distribution of the right supraorbital and supratrochlear nerves. The authors diagnosed as a delayed SOFS and prescribed 4 mg of methylprednisolone q.i.d. for 30 days. After steroid therapy, extraocular movement limitations improved progressively. After 8 months, movement was completely restored. The authors experienced delayed SOFS on posttrauma day 27, and it was treated by steroid therapy. Surgical intervention is required when there is an evident etiology such as underlying hematoma or plate migration. If the reason is not clear like our case, steroid therapy can be considered as one of the options. Particularly, the authors should give special attention to the patient who has congenitally narrow superior orbital fissure, like Fujiwara et al suggested. PMID- 26674905 TI - Rehabilitation of Atrophied Low-Density Posterior Maxilla by Implant-Supported Prosthesis. AB - The rehabilitation of edentulous posterior maxilla is a challenging task that could be complicated by the availability of low-density and reduced height of alveolar bone. Patients were enrolled in this study upon the presence of type IV bone and residual bone height <5 mm in posterior maxilla. Novel procedure for transalveolar sinus floor elevation was described to insert 10 short implants in 4 patients. Neither implant failure nor prosthetic failure was observed during a follow-up of 44 +/- 3 months. Mesial bone loss of 0.5 +/- 0.6 mm and a distal bone loss 1.3 +/- 0.9 mm were measured after 35 +/- 4 months of loading. PMID- 26674906 TI - The Management for Intracranial Metastatic Neuroendocrine Tumor With Lung Origin. AB - Neuroendocrine tumor (NET) is not a common source of brain metastasis and the standard management of intracranial metastatic NET with lung origin remains unclear as a result of its rarity. We aimed to generalize some applicable protocols from our current 2 cases and relevant literature. PMID- 26674907 TI - Eggshell-Derived Hydroxyapatite: A New Era in Bone Regeneration. AB - BACKGROUND: Defects of maxillofacial skeleton lead to personal (functional and aesthetic), social and behavioral problems; which make the person to isolate from the main stream of society. So, bone regeneration is the need for proper structure, function, and aesthetics following cyst enucleation, trauma, and tumor ablative surgery; which helps for overall health of the individual. AIM AND OBJECTIVES: The preliminary study is planned to evaluate and compare the efficacy of eggshell-derived hydroxyapatite (EHA) and synthetic hydroxyapatite (SHA) following cystectomy. MATERIAL AND METHODS: Microwave-processed calcium deficient EHA and commercially available SHA are used for grafting. Total 20 patients enrolled in this study, consisting 10 in each group between 20 and 45 years of age. All the patients were evaluated for bone regeneration at first, second, third, and sixth month's interval, postsurgically, using radiovisiograph and clinical parameters. RESULTS: The bone formation characteristics vary at second month when compared to SHA. This difference may be because of the kinetics involved in the regeneration pattern. The pattern of bone healing was trabecular after third month, indicating complete bone formation. The study showed constant raise of density and remained same at the end of study period. CONCLUSIONS: Both EHA and SHA graft materials are equally efficient in early bone regeneration. Within the limitations of this study the EHA showed promising results. Which indicates the eggshell waste-bio mineral is worthwhile raw material for the production of HA and is a Go Green procedure. Eggshell-derived hydroxyapatite is economic, compared with SHA. PMID- 26674908 TI - A Novel Technique for Short Nose Correction: Hybrid Septal Extension Graft. AB - BACKGROUND: There are many techniques for correcting short nose deformities and the septal extension graft is the most commonly performed technique among Asians. In many Asian patients septal cartilage, however, is too small and insufficient to perform an effective septal extension graft. Therefore, we designed a novel technique, named hybrid septal extension graft to overcome this pitfall in Asian tip plasty. METHODS: From February 2010 to March 2013, 41 patients with primary (N = 30) or secondary (N = 11) short nose deformity underwent a hybrid septal extension graft. The hybrid septal extension graft is a modified septal extension graft which uses the small septal cartilage along with irradiated homologous costal cartilage. Irradiated homologous costal cartilage was carved into a shape of a thin batten and securely fixed bilaterally to the caudal septum. Harvested septal cartilage was located between the 2 irradiated homologous costal cartilage batten grafts and fixed with sutures. Then, the alar cartilage was fixed at the end of the septal cartilage graft. The nasal lengths, nasal tip projections, and nasolabial angles were measured pre- and postoperatively. RESULTS: The hybrid septal extension graft showed enough nose lengthening and a decreased nostril show, even in cases with a very small septal cartilage. CONCLUSIONS: The authors present a novel technique for correction of short nose deformity in Asians. The hybrid septal extension graft provides good results with minimal complications and overall patient satisfaction was very high. PMID- 26674909 TI - Posterior Pharyngeal Flap for Velopharyngeal Insufficiency Patients: A New L Shaped Flap. AB - OBJECTIVE: To describe and assess the results of central inset L-shaped posterior pharyngeal flap (PF) for treatment of velopharyngeal incompetence. METHODS: This study included 12 patients who were diagnosed as persistent velopharyngeal insufficiency. L-shaped central inset superiorly based PF was harvested from oropharynx and inserted into the soft palate through a transverse full-thickness palatal incision 1 cm behind the posterior margin of the hard palate, then the flap was spread 1 cm horizontally and 1 cm in the anteroposterior direction in soft palate. Before and after surgery, patients were assessed by examination, video: nasoendoscopy, and speech assessment. RESULTS: Postoperative speech assessment showed significant improvement in the nasal emission, resonance, intraoral pressure, and articulation defects. Grade 4 velopharyngeal valve closure (complete closure) could be achieved in all patients. No patients showed dehiscence (partial or total) of the flap and no obstructive sleep apnea reported. CONCLUSIONS: The new used L-shaped PF could properly correct velopharyngeal functions (closure and speech) in patients with persistent velopharyngeal insufficiency with no reported complication. PMID- 26674910 TI - Surgical Correction of an Extensive Skull Base Defect as a Result of Pneumocele. AB - Pneumocele is a condition involving the pathologic expansion of paranasal sinuses with corresponding bony erosion of the skull base. Extensive pneumocele can lead to pneumocephalus, especially in patients with long-term cerebrospinal fluid shunts. Here, the authors present a case of pneumocele in an adult with a history of congenital hydrocephalus managed with a ventriculoperitoneal shunt. The patient underwent reconstruction of a posterior table defect with a pericranial flap followed by frontal sinus obliteration with abdominal fat. PMID- 26674912 TI - Management of the Airway in Apert Syndrome. AB - The management of the airway in Apert syndrome is complex and multidisciplinary. This rare syndrome, occurring in up to approximately 1 in 65,000 live births, results in airway compromise at various anatomic levels, in addition to abnormal central respiratory drive. Obstructive apneas arise because of decreased airway caliber, which may occur in the form of congenital bony nasal stenosis, choanal atresia, a deviated nasal septum, a narrowed nasopharynx, a thick long soft palate, lateral palatal swellings, and a tracheal cartilage sleeve. Central apneas in Apert syndrome arise because of raised intracranial pressure and/or Chiari malformations. The purpose of this study was to investigate our treatment methods and outcomes in optimizing the airway in this complex, rare and interesting cohort of patients who present with airway compromise. Patients with Apert syndrome were retrospectively evaluated during a period from 1990 to 2013. Treatments for obstructive apnea were dilatation of nasal airways and choanal atresia repair, adenoidectomy, tonsillectomy, early midface advancement, and noninvasive ventilation. The insertion of ventriculoperitoneal shunts, fronto orbital advancement, and Chiari decompression aid in managing central apneas. The authors present our experience at Alder Hey Children's Hospital, Liverpool, one of the 4 Supraregional Craniofacial Units in the United Kingdom. PMID- 26674913 TI - Comparative Study of Naugle and Hertel Exophthalmometry in Orbitozygomatic Fracture. AB - Accurate perioperative evaluation of enophthalmos is important to determine the adequacy of surgical repair in orbitozygomatic fracture. In this study, the authors evaluated the degree of enophthalmos using Hertel and Naugle exophthalmometry in patients with pure blowout fracture and orbitozygomatic fracture, and compared the results. Fifty patients were divided into 2 groups: pure blowout fracture (Group A: control group, 25 patients) and orbitozygomatic fracture with displaced lateral orbital rim (Group B: experimental group, 25 patients). Hertel and Naugle scales were measured before and 6 months after surgery. The degree of lateral orbital rim advancement was assessed by comparing the difference between the perioperative change of the Hertel and Naugle scales. In Group A, the difference between the pre- and postoperative scales in the 2 exophthalmometry was statistically significant (P < 0.05). In Group B, the Hertel scale increased from -0.20 to -0.16 mm, with an insignificant difference between pre- and postoperative values (P > 0.05) and the Naugle scale increased from 0.88 to -0.20 mm, with a significant difference (P < 0.05). The Delta Hertel scale differed from the Delta Naugle scale by a mean of -0.64 mm, which represents the degree of lateral orbital rim advancement. Naugle exophthalmometry is a more reliable method for evaluation of enophthalmos in lateral orbital rim displaced orbitozygomatic fractures than Hertel exophthalmometry. The degree of lateral orbital rim advancement can be assessed by combined use of the Hertel and Naugle exophthalmometry in orbitozygomatic fractures. PMID- 26674914 TI - Augmentation Genioplasty Using Double Folded Dermal Graft. AB - INTRODUCTION: The chin is a very important aesthetic subunit of the face. The diverse materials and methods for chin augmentation can be classified according to autologous tissues and artificial ones. Among them, reports on the effectiveness of dermal graft for chin augmentation are scarce. The authors report on our new techniques and surgical results regarding chin augmentation using a dermal graft. PATIENTS AND METHODS: From July 2010 to January 2013, the authors performed supraperiosteal chin augmentation using a double folded dermal graft for 58 patients (15 men and 43 women; range of age: 20-45, average was 29.4). Periodic sonography was performed routinely to measure the change of thickness of the dermal graft (preoperative, postoperatively 1, 6, and 12 months). RESULTS: Thickness of the survived dermal graft was 8.33 +/- 1.21 mm and 7.99 +/- 1.19 mm at postoperative 6 and 12 months separately. Statistics showed that the average resorption rate was 32.17% (SD = 10.99) at postoperative 6 months and 34.93% (SD = 10.74) at postoperative 12 months. Of 56 patients 54 (2 patients were excluded from the study) did not request additional surgery during the 3-year follow-up period and showed a high level of satisfaction with the surgical results. CONCLUSIONS: The authors consider that our unique design and surgical techniques of double folded dermal graft have many advantages and provide consistent evidence-based results to meet patients' desire for a natural appearance after chin augmentation, particularly patients who refuse to get artificial implants. PMID- 26674915 TI - Correlation Between the Septal Body and the Nasal Turbinates in Patients With Deviated Nasal Septum. AB - OBJECTIVE: The purpose of this study was to evaluate the degree of deviation and the sizes of nasal turbinates and the septal body (SB) on each side separately and to compare the 2 sides, and to evaluate if there is a correlation between SB size and middle and inferior turbinate (IT) sizes on each side. MATERIAL AND METHODS: A retrospective analysis was made of paranasal computerized tomography scans obtained randomly from the database. Computerized tomography was performed at 120 kVp and 100 mA with 2 mm slice thickness. The study comprised 199 paranasal computerized tomography scans on each of which the width of the SB, the degree of deviation, and the width of the inferior and middle turbinates (MTs) were measured on each side separately. RESULTS: In cases of moderate and severe deviation, the sizes of the SB, the MT, and IT contralateral to the deviation were statistically significantly larger than those on the ipsilateral side (P < 0.001). There was a negative correlation between SB size and the MT and IT sizes in each nasal cavity. CONCLUSIONS: The SB is a dynamic structure and may play a role in regulation of nasal airflow. PMID- 26674917 TI - Comparison of Local Recurrence Rate of Three Treatment Modalities for Kimura Disease. AB - Eosinophilic hyperplastic lymphogranuloma, also known as Kimura disease, is a benign and chronic inflammatory condition, predominantly involving the head and neck region. Surgical excision, radiotherapy (RA), surgical resection combined with low-dose postoperative radiotherapy and oral corticosteroids are 4 treatment modalities reported to control this disease effectively. Local recurrence, however, is common and the optimum treatment for Kimura disease is controversial. Thus, the present meta-analysis was performed to identify the treatment modality associated with the lowest local recurrence. Electronic databases (Cochrane Library, Wiley Online Library, PubMed, Chinese National Knowledge Infrastructure, and Wanfang Data) were searched. Data were also obtained from other sources such as related references and communication with the relevant authors. Two reviewers screened the literature according to preselected criteria. All studies involving different treatments for Kimura disease were collected. After data extraction and research quality assessment, the meta-analysis of 22 studies involving 570 patients was conducted using STATA 12.1 software. Meta-analysis revealed that administration of RA or surgical excision alone were inferior in controlling local recurrence compared with surgical resection combined with postoperative RA (risk ratio (RR) = 2.72; 95% confidence interval (CI), 1.47-5.04 and RR = 4.72; 95% CI, 2.53-8.82). Surgical excision alone did not show significant advantage in controlling local recurrence compared with RA alone (RR = 2.13; 95% CI, 0.88 5.17). Surgical resection combined with postoperative RA is superior to either surgery or RA alone in treating Kimura disease. More large scale prospective randomized controlled trials, however, should be conducted to assess the long term effects and safety issues. PMID- 26674916 TI - Effect of Reflection of Temporalis Muscle During Cranioplasty With Titanium Mesh After Standard Trauma Craniectomy. AB - Cranioplasty (CP) with titanium mesh after standard trauma craniectomy (STC) has been proven to be a favorable technology. According to reflection of temporalis muscle or not, the CP was divided into 2 operation ways. Effect of reflection of temporalis muscle has not been systematically researched. Thirty-nine patients were enrolled to assess the effect of reflection of temporalis muscle during CP after STC. Cranial index of symmetry was adopted to evaluate the aesthetic results, transcranial Doppler was used to assess change of cerebral blood flow (CBF), functional independence measurements were performed to monitor the improvement of neuronal function, and complications associated with CP were also recorded. The results displayed that reflection of temporalis muscle or not had no effect on the anesthetic results. Both operation ways could improve CBF and neuronal function. Cranioplasty with reflection of temporalis muscle could improve CBF and neuronal function more significantly. Furthermore, reflection of temporalis muscle would not increase complications associated with CP. Reflection of temporalis muscle during CP with titanium mesh after STC proves to be an effective and safe operation way. PMID- 26674918 TI - Nonfatal Cervical-Neck Lesion With a Wooden Foreign Body: Diagnosis and Management. AB - Penetrating cervical lesions caused by a foreign body are rare events. The neck is a complex and delicate body region, given the important vascular structures it holds. The most frequent fatal complications often involve vascular injuries, and as a consequence, the mortality rate increases by approximately 50%. Civilian patients are mainly victims of violence or motor vehicle accidents and rural accidents involving neck are not very common. When a cervical lesion is because of a wooden foreign body, infectious risk increases for its organic peculiarity. The authors report a rural nonfatal cervical lesion in a civilian, and its management. PMID- 26674919 TI - Morphologic Study of Superior Temporal Sulcus-Amygdaloid Body and Lateral Fissure Amygdaloid Body Surgical Approach by Using Magnetic Resonance Imaging Volume Rendering. AB - In this research, 83 patients were measured by magnetic resonance imaging volume rendering technique. The authors acquired the curve length of the superior temporal sulcus and the lateral fissure on the cerebral hemisphere, the shortest distance from the superior temporal sulcus and the lateral fissure to the center of amygdaloid body separately, the vertical diameter, the transversal diameter, and the anteroposterior diameter of the amygdaloid body and the 2 approach angles between the median sagittal plane and the shortest segment from the superior temporal sulcus to the center of amygdaloid body and the shortest segment from lateral fissure to the center of the amygdaloid body. At the same time, we preliminarily oriented the 2 points of the superior temporal sulcus and the lateral fissure, which are closest to the center of amygdaloid body, aimed at finding out the best entrance points of surgical approach through the superior temporal sulcus and the lateral fissure to the amygdaloid body and reducing the damage to the nerve fibers or blood vessels during the operation. The results indicate that the point at the front side 1/4 of the superior temporal sulcus may be the ideal surgical approach entrance point and the point at the front side 1/3 of the lateral fissure. There is no difference between 2 cerebral hemispheres (P < 0.05). PMID- 26674920 TI - Trigeminal Neuralgia Caused by Cerebellopontine Angle Arteriovenous Malformation Treated With Gamma Knife Radiosurgery. AB - Trigeminal neuralgia is a facial pain syndrome characterized as sudden onset and lightening-like sensation over somatosensorial branch(es) of fifth cranial nerve. Rarely, some underlying diseases or disorders could be diagnosed, such as multiple sclerosis, brain tumors, and vascular malformations. The authors present a 47-year-old man with trigeminal neuralgia over left V2 and V3 dermatomes. He had a previous transarterial embolization and long use of carbamazepine with partial response to treatment. Gamma knife radiosurgery (GKR) was planned. A marginal dose of 15 Gy was given to 50% isodose line. His pain was relieved by GKR in 1.5 years. Treatment of posterior fossa arteriovenous malformations causing trigeminal neuralgia, with GKR has a very limited use in the literature. It, however, is obvious that success rate as pain relief, in a very challenging field of functional neurosurgery, is satisfactory. Large series, however, are in need to make a more comprehensive statement about efficacy and safety of the procedure in these pathologies. PMID- 26674921 TI - Application of high-frequency ultrasonography in closing small blood vessels. AB - One of the most common treatments performed in phlebological and aesthetic medicine clinics is closing small blood vessels in the lower extremities, so called telangiectasias and reticular vessels. Currently, there are several methods that allow for closing the dilated vessels and obtaining desirable effects, both therapeutic and aesthetic. Unfortunately, despite applying various methods and instruments, the effects of treatments are frequently not satisfactory. The factor that largely contributes to decreasing the efficacy of such procedures is complicated anatomy of the venous system and the lack of a method to precisely specify the vessel's course, its diameter, location in the skin etc. High-frequency ultrasonography is a method enabling accurate determination of the vessels' course as well as the measurement of their basic parameters, such as diameter, depth in the skin and presence or absence of perfusion. Thanks to ultrasound imaging with the use of high-frequency transducers, an adequate treatment method and procedure parameters may be selected, which entails enhancing the efficacy of the procedure itself. Ultrasonography may be also used for monitoring the performed procedures. PMID- 26674922 TI - Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker. AB - BACKGROUND: Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways. METHODS: We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case-control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n = 253) and a secondary cross-sectional cohort (over 65s; n = 649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender. CONCLUSIONS: Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines. GENERAL SIGNIFICANCE: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker. PMID- 26674923 TI - Incidence and relapse risk of intracranial metastases within the perihippocampal region in 314 patients with breast cancer. AB - PURPOSE: The safe prerequisite of hippocampal-sparing whole brain radiotherapy (HS-WBRT) for patients with breast cancer is unclear. This study investigated the risk and relapse of perihippocampal (PH) metastases in breast cancer. METHODS: Consecutive breast cancer patients with brain metastasis (BM) were reviewed. Metastases and hippocampi were contoured in cranial magnetic resonance imaging (MRI). The closest distance from metastasis to hippocampus was calculated. Clinical and radiographic variables were correlated with PH (in or within 5mm around the hippocampus) metastasis. The risk of post-treatment PH recurrence was estimated. RESULTS: Three hundred and fourteen patients with 1678 metastases exhibited a median breast cancer-specific overall survival (OS) and OS after BM (BMOS) of 75.4 and 14.3 months, respectively. Hippocampal metastases were identified in 1.2% of metastases and 4.1% of patients. PH lesions comprised 3.5% of lesions in 11.1% of patients. The number and aggregated volume of BM were associated with PH disease probability (univariate). Only the number of BM significantly correlated with PH disease in the multivariate analysis. The patients with PH lesions exhibited more non-oligometastatic disease, increased tumor volume, and poor BMOS. One hundred and eleven patients without original PH lesions developed intracranial progression post-treatment. The risks of PH metastasis recurrence were 4.6% for WBRT and 6.8% for sub-therapeutic irradiation in the PH region. The increase in the absolute risk of PH recurrence with hippocampal-sparing irradiation was approximately 2%. CONCLUSIONS: These novel findings indicate that BM from breast cancer exhibits low risks of metastases and relapse within the hippocampal avoidance region. Non-oligometastatic disease is associated with PH metastasis. Thus, HS-WBRT is considered safe and suitable for breast cancer. PMID- 26674925 TI - A New Device to Place Elastic Separators. AB - Separation of teeth is an important and integral aspect of orthodontic treatment. Elastomeric separators are the most common devices used today which require special instrument to place them. The purpose of this study was to design a separator placing instrument of dental probe/explorer which can be used as an alternative to the special instrument required. The materials required were two dental probes/explorers, a light wire plier and elastomeric separators. The modified instrument made is easy to fabricate, inexpensive and can partially or completely replace the special separator placing plier. PMID- 26674924 TI - [(18)F]Fluoro-2-deoxy-2-d-glucose versus 3'-deoxy-3'-[(18)F]fluorothymidine for defining hematopoietically active pelvic bone marrow in gynecologic patients. AB - BACKGROUND AND PURPOSE: We compared [(18)F]fluoro-2-deoxy-2-d-glucose (FDG) versus 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) for the purpose of identifying active pelvic bone marrow (BM), quantifying its locational variation, and determining which technique is likely to be better for BM-sparing radiation planning. MATERIAL AND METHODS: We sampled 41 patients, of which 25 underwent FDG PET/CT only, 7 underwent FLT-PET/CT only, and 9 underwent both. Active BM subvolumes were defined as subsets of the pelvic BM with the highest standardized uptake values comprising 40%, 50%, and 60% of the total pelvic BM volume. We used the Dice similarity coefficient to quantify the percent overlap of active BM volumes of equal size. Differences in the spatial distribution of active BM were assessed using a region-growing algorithm. RESULTS: For patients with both modalities, the mean Dice coefficients for the 40%, 50%, and 60% subvolumes were 0.683, 0.732, and 0.781 respectively. Comparing individual active BM subvolumes to the mean subvolume, Dice coefficients varied from 0.598-0.889 for FDG and 0.739-0.912 for FLT. Region growing analysis showed FLT-PET defined more highly clustered active BM subvolumes. CONCLUSIONS: Within the limitations of a small sample size, we found significant agreement between FDG-PET and FLT-PET; however, FLT-PET had significantly less individual variation and is likely to be superior to FDG-PET for BM-sparing radiotherapy. PMID- 26674926 TI - Endoscopy in neutropenic and/or thrombocytopenic patients. AB - AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm(3) in four studies and less than 10000/mm(3) in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm(3) in one study and less than 20000/mm(3) in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm(3) in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be considered in some cases and should be individualized. PMID- 26674927 TI - Neutrophil CD64 expression is not a useful biomarker for detecting serious bacterial infections in febrile children at the emergency department. AB - BACKGROUND: CD64 is expressed on the surface membrane of neutrophils (nCD64) in the presence of bacterial infection. Although initial studies in intensive care settings have been promising, only two small, methodologically flawed studies have been performed in feverish children presenting to the emergency department (ED), both of which were showing a moderate diagnostic value of nCD64 to detect a serious bacterial infection (SBI). This study aimed to determine the diagnostic value of nCD64 in children presenting with fever to the ED for detecting SBI. METHODS: In this prospective observational multi-centre study previously healthy children aged 1 month-16 years with fever, presenting to the ED of two hospitals in the Netherlands in 2011-2012 were included. Standardised information on clinical features were collected and nCD64 and CRP were measured routinely. Multivariable logistic regression was used to determine the discriminative ability to detect SBI (ROC-area) of nCD64 compared with CRP. Diagnostic performance measures including sensitivity, specificity and likelihood ratios were calculated. RESULTS: In 392 children (45%) with both CRP and nCD64 determined, 52 children (13%) had an SBI. The AUC of the ROC curve for CD64 was 0.62 (95% CI = 0.54-0.70) and 0.75 (95% CI = 0.67-0.83) for CRP. Neither duration of fever nor deviated vital signs influenced the diagnostic performance of nCD64. CONCLUSION: NCD64 expression has poor discriminative value to detect children with an SBI in a general population of febrile children at the ED. It has no superior value compared to CRP in this setting, neither in total nor in sub populations. PMID- 26674929 TI - Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane. AB - OBJECTIVES: Squamous cell carcinoma (SCC) is the most common oral malignancy, and verrucous carcinoma (VC) is a less invasive type of SCC. Leukoplakia (LP) is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV) has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high risk subtypes (HPV HR) has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions. METHODS: One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs) and 18 normal mucosa samples (as a control group) were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction. RESULTS: The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%), we observed the presence of HPV HR (types 16 and 18). All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230). Additionally, 15 (13.1%) SCCs showed HPV positivity, but this was not significant (p=0.830). The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11). A statistically significant association was not observed between HPV and SCC or VC in the oral cavity. CONCLUSION: More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions. PMID- 26674928 TI - TSI ultrasound elastography for the diagnosis of chronic allograft nephropathy in kidney transplanted patients. AB - PURPOSE: To answer the question whether the TSI (tissue strain imaging) sonoelastography technique can contribute to the diagnosis of chronic renal allograft damage. MATERIAL AND METHODS: A prospective study of 112 patients between June 2010 and April 2011 was conducted to compare elastography data with biopsy results and laboratory parameters in order to determine whether any correlations exist. Elastography parameters were acquired with a high-end ultrasound system and analyzed using the semiquantitative strain ratio. For comparison, patients were divided into three groups based on biopsy findings (Banff classification): group A: biopsy not necessary; group B: Banff grade I; group C: Banff grades II and III. Correlations were assessed by means of correlation (Pearson) and regression analysis. Differences between ordinal groups were tested for statistical significance by the Mann-Whitney U test. RESULTS: Mean patient age was 54.2 +/- 15.01 years. Fifty-nine percent of the patients were male. The calculated TSI strain ratio of groups A and C differed significantly (p = 0.024). Groups B and C (p = 0.056) and groups A and B (p = 0.88) showed no significant difference. The TSI strain ratio did not correlate with glomerular filtration rate (r = 0.105) or creatinine (r = 0.092). CONCLUSION: The TSI sonoelastography technique can contribute to the differentiation of different stages of renal graft damage (according to Banff classification). However, significant results were not observed for all investigated features. The TSI technique should be further evaluated in future studies including larger numbers of patients. PMID- 26674930 TI - Loop-mediated Isothermal Amplification Assay to Rapidly Detect Wheat Streak Mosaic Virus in Quarantined Plants. AB - We developed a loop-mediated isothermal amplification (LAMP) method to rapidly diagnose Wheat streak mosaic virus (WSMV) during quarantine inspections of imported wheat, corn, oats, and millet. The LAMP method was developed as a plant quarantine inspection method for the first time, and its simplicity, quickness, specificity and sensitivity were verified compared to current reverse transcription-polymerase chain reaction (RT-PCR) and nested PCR quarantine methods. We were able to quickly screen for WSMV at quarantine sites with many test samples; thus, this method is expected to contribute to plant quarantine inspections. PMID- 26674931 TI - Cancer Mortality Among People Living in Areas With Various Levels of Natural Background Radiation. AB - There are many places on the earth, where natural background radiation exposures are elevated significantly above about 2.5 mSv/year. The studies of health effects on populations living in such places are crucially important for understanding the impact of low doses of ionizing radiation. This article critically reviews some recent representative literature that addresses the likelihood of radiation-induced cancer and early childhood death in regions with high natural background radiation. The comparative and Bayesian analysis of the published data shows that the linear no-threshold hypothesis does not likely explain the results of these recent studies, whereas they favor the model of threshold or hormesis. Neither cancers nor early childhood deaths positively correlate with dose rates in regions with elevated natural background radiation. PMID- 26674932 TI - Choosing GnRH Antagonist Protocol Shows Improved Oocyte and Embryo Quality, Coherent with the Perifollicular Vascularity (PFV) in Assisted Reproductive Techniques. AB - INTRODUCTION: The parent oocyte from which the embryo is derived, determines its quality and the perifollicular vascularity (PFV) determines the micro-environment of the developing ovum. The PFV correlates well with the follicular oxygenation, oocyte maturation and embryo viability. PFV is imaged with Power Doppler Ultrasound. AIM: To study and compare the association of the PFV of follicles with the quality of the oocytes and embryos in agonist and antagonist protocol, employed in Assisted Reproductive techniques (ART). STUDY DESIGN: A prospective observational study was conducted on 75 patients, who were recruited for ART cycles, out of which 25 were given the Agonist protocol and the remaining 50 received the Antagonist protocol. MATERIALS AND METHODS: The patients underwent the stimulation protocol. The PFV of preovulatory follicles were studied with Transvaginal Power Doppler and graded. Each oocyte retrieved carried the same label of its parent follicle. Embryos were cultured. The embryologist was blinded. The oocyte and embryo quality were assessed and compared with the PFV of parent follicle. RESULTS: Follicles with grade 1 and 2 PFV were predominantly observed. The yield of oocytes was independent of PFV. The mean yield of good quality embryos in conjunction with the PFV of the parent follicle was found to be highly significant in both the groups. The antagonist group had statistically significant yield of mature oocytes and embryos, compared to the agonist group. CONCLUSION: Antagonist protocol had favourable outcomes compared with the agonist protocol. The retrieval of oocytes, even the mature ones and the yield of high grade embryos were found higher. As the PFV increased, the yield and overall pregnancy rates were higher. PFV as assessed by Power Doppler is a useful non invasive biomarker of embryo quality and can be employed in conjunction with other biomarkers in ART to predict successful outcome. PMID- 26674933 TI - Crocin, a carotenoid component of Crocus cativus, exerts inhibitory effects on L type Ca(2+) current, Ca(2+) transient, and contractility in rat ventricular myocytes. AB - Crocin, a carotenoid component of Crocus sativus L. belonging to the Iridaceae family, has demonstrated cardioprotective effects. To investigate the cellular mechanisms of these cardioprotective effects, here we studied the influence of crocin on L-type Ca(2+)current (I(Ca-L)), intracellular Ca(2+) ([Ca(2+)]i), and contraction of isolated rat cardiomyocytes by using the whole-cell patch-clamp technique and video-based edge detection and dual excitation fluorescence photomultiplier systems. Crocin inhibited I(Ca-L) in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) of 45 MUmol/L and the maximal inhibitory effect of 72.195% +/- 1.54%. Neither current-voltage relationship of I(Ca-L), reversal potential of I(Ca-L), nor the activation/inactivation of I(Ca-L) was significantly changed. Crocin at 1 MUmol/L reduced cell shortening by 44.64% +/- 2.12% and the peak value of the Ca(2+) transient by 23.66% +/- 4.52%. Crocin significantly reduced amplitudes of myocyte shortening and [Ca(2+)]i with an increase in the time to reach 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of crocin may be attributed to the attenuation of [Ca(2+)]i through the inhibition of I(Ca-L) in rat cardiomyocytes and negative inotropic effects on myocardial contractility. PMID- 26674943 TI - Family Planning Practices, Programmes and Policies in India Including Implants and Injectables with a Special Focus on Jharkhand, India: A Brief Review. AB - The National Family Health Survey (NFHS)-3 clearly delineates that the usage of contraceptive practices has increased considerably but is more inclined toward terminal methods of contraception especially the female sterilization. The fact is also evident from various studies carried out from time to time in different Indian states. Given the context we carried out a short review to understand the family planning practices, programs and policies in India including implants and injectable contraceptives with a special focus on the state of Jharkhand. We found that among the reversible methods IUCD (intra uterine contraceptive devices), OC (oral contraceptive) pills and condoms are the most commonly used methods. In this review, in addition to national picture, we specially focused on the state of Jharkhand owing to its very gloomy picture of family planning practices as per NFHS -3 reports. The current usage of any methods of contraception in Jharkhand is only 35.7% out of which terminal methods especially female sterilization accounts to 23.4% and male sterilization being only 0.4%. Similar picture is also reflected in the conventional methods such as; IUCD-0.6%, oral pill -3.8% and condom-2.7%. Compared to the national figure the unmet need for family planning in Jharkhand is also relatively high for the conventional reversible methods than that of terminal methods which is 11.9 and 11.3 respectively. Injectable contraceptives are available only through private or social marketing channels, because of which their use is limited. The studies carried out in different Indian states show improvement in contraceptive prevalence but the same needs further improvement. PMID- 26674945 TI - The evolutionary convergence of avian lifestyles and their constrained coevolution with species' ecological niche. AB - The fit between life histories and ecological niche is a paradigm of phenotypic evolution, also widely used to explain patterns of species co-occurrence. By analysing the lifestyles of a sympatric avian assemblage, we show that species' solutions to environmental problems are not unbound. We identify a life-history continuum structured on the cost of reproduction along a temperature gradient, as well as habitat-driven parental behaviour. However, environmental fit and trait convergence are limited by niche filling and by within-species variability of niche traits, which is greater than variability of life histories. Phylogeny, allometry and trade-offs are other important constraints: lifetime reproductive investment is tightly bound to body size, and the optimal allocation to reproduction for a given size is not established by niche characteristics but by trade-offs with survival. Life histories thus keep pace with habitat and climate, but under the limitations imposed by metabolism, trade-offs among traits and species' realized niche. PMID- 26674944 TI - Striking cuticular hydrocarbon dimorphism in the mason wasp Odynerus spinipes and its possible evolutionary cause (Hymenoptera: Chrysididae, Vespidae). AB - Cleptoparasitic wasps and bees smuggle their eggs into the nest of a host organism. Here the larvae of the cleptoparasite feed upon the food provision intended for the offspring of the host. As cleptoparasitism incurs a loss of fitness for the host organism (offspring of the host fail to develop), hosts of cleptoparasites are expected to exploit cues that alert them to potential cleptoparasite infestation. Cuticular hydrocarbons (CHCs) could serve as such cues, as insects inevitably leave traces of them behind when entering a nest. By mimicking the host's CHC profile, cleptoparasites can conceal their presence and evade detection by their host. Previous studies have provided evidence of cleptoparasites mimicking their host's CHC profile. However, the impact of this strategy on the evolution of the host's CHC profile has remained unexplored. Here, we present results from our investigation of a host-cleptoparasite system consisting of a single mason wasp species that serves syntopically as the host to three cuckoo wasp species. We found that the spiny mason wasp (Odynerus spinipes) is able to express two substantially different CHC profiles, each of which is seemingly mimicked by a cleptoparasitic cuckoo wasp (i.e. Chrysis mediata and Pseudospinolia neglecta). The CHC profile of the third cuckoo wasp (Chrysis viridula), a species not expected to benefit from mimicking its host's CHC profile because of its particular oviposition strategy, differs from the two CHC profiles of its host. Our results corroborate the idea that the similarity of the CHC profiles between cleptoparasitic cuckoo wasps and their hosts are the result of chemical mimicry. They further suggest that cleptoparasites may represent a hitherto unappreciated force that drives the evolution of their hosts' CHCs. PMID- 26674946 TI - Ocean acidification boosts larval fish development but reduces the window of opportunity for successful settlement. AB - Locating appropriate settlement habitat is a crucial step in the life cycle of most benthic marine animals. In marine fish, this step involves the use of multiple senses, including audition, olfaction and vision. To date, most investigations of larval fish audition focus on the hearing thresholds to various frequencies of sounds without testing an ecological response to such sounds. Identifying responses to biologically relevant sounds at the development stage in which orientation is most relevant is fundamental. We tested for the existence of ontogenetic windows of reception to sounds that could act as orientation cues with a focus on vulnerability to alteration by human impacts. Here we show that larvae of a catadromous fish species (barramundi, Lates calcarifer) were attracted towards sounds from settlement habitat during a surprisingly short ontogenetic window of approximately 3 days. Yet, this auditory preference was reversed in larvae reared under end-of-century levels of elevated CO2, such that larvae are repelled from cues of settlement habitat. These future conditions also reduced the swimming speeds and heightened the anxiety levels of barramundi. Unexpectedly, an acceleration of development and onset of metamorphosis caused by elevated CO2 were not accompanied by the earlier onset of attraction towards habitat sounds. This mismatch between ontogenetic development and the timing of orientation behaviour may reduce the ability of larvae to locate habitat or lead to settlement in unsuitable habitats. The misinterpretation of key orientation cues can have implications for population replenishment, which are only exacerbated when ontogenetic development decouples from the specific behaviours required for location of settlement habitats. PMID- 26674947 TI - Fossils and living taxa agree on patterns of body mass evolution: a case study with Afrotheria. AB - Most of life is extinct, so incorporating some fossil evidence into analyses of macroevolution is typically seen as necessary to understand the diversification of life and patterns of morphological evolution. Here we test the effects of inclusion of fossils in a study of the body size evolution of afrotherian mammals, a clade that includes the elephants, sea cows and elephant shrews. We find that the inclusion of fossil tips has little impact on analyses of body mass evolution; from a small ancestral size (approx. 100 g), there is a shift in rate and an increase in mass leading to the larger-bodied Paenungulata and Tubulidentata, regardless of whether fossils are included or excluded from analyses. For Afrotheria, the inclusion of fossils and morphological character data affect phylogenetic topology, but these differences have little impact upon patterns of body mass evolution and these body mass evolutionary patterns are consistent with the fossil record. The largest differences between our analyses result from the evolutionary model, not the addition of fossils. For some clades, extant-only analyses may be reliable to reconstruct body mass evolution, but the addition of fossils and careful model selection is likely to increase confidence and accuracy of reconstructed macroevolutionary patterns. PMID- 26674948 TI - Intrinsic and realized generation intervals in infectious-disease transmission. AB - The generation interval is the interval between the time when an individual is infected by an infector and the time when this infector was infected. Its distribution underpins estimates of the reproductive number and hence informs public health strategies. Empirical generation-interval distributions are often derived from contact-tracing data. But linking observed generation intervals to the underlying generation interval required for modelling purposes is surprisingly not straightforward, and misspecifications can lead to incorrect estimates of the reproductive number, with the potential to misguide interventions to stop or slow an epidemic. Here, we clarify the theoretical framework for three conceptually different generation-interval distributions: the 'intrinsic' one typically used in mathematical models and the 'forward' and 'backward' ones typically observed from contact-tracing data, looking, respectively, forward or backward in time. We explain how the relationship between these distributions changes as an epidemic progresses and discuss how empirical generation-interval data can be used to correctly inform mathematical models. PMID- 26674950 TI - An ambusher's arsenal: chemical crypsis in the puff adder (Bitis arietans). AB - Ambush foragers use a hunting strategy that places them at risk of predation by both visual and olfaction-oriented predators. Resulting selective pressures have driven the evolution of impressive visual crypsis in many ambushing species, and may have led to the development of chemical crypsis. However, unlike for visual crypsis, few studies have attempted to demonstrate chemical crypsis. Field observations of puff adders (Bitis arietans) going undetected by several scent orientated predator and prey species led us to investigate chemical crypsis in this ambushing species. We trained dogs (Canis familiaris) and meerkats (Suricata suricatta) to test whether a canid and a herpestid predator could detect B. arietans using olfaction. We also tested for chemical crypsis in five species of active foraging snakes, predicted to be easily detectable. Dogs and meerkats unambiguously indicated active foraging species, but failed to correctly indicate puff adder, confirming that B. arietans employs chemical crypsis. This is the first demonstration of chemical crypsis anti-predatory behaviour, though the phenomenon may be widespread among ambushers, especially those that experience high mortality rates owing to predation. Our study provides additional evidence for the existence of an ongoing chemically mediated arms race between predator and prey species. PMID- 26674949 TI - Interactions among bacterial strains and fluke genotypes shape virulence of co infection. AB - Most studies of virulence of infection focus on pairwise host-parasite interactions. However, hosts are almost universally co-infected by several parasite strains and/or genotypes of the same or different species. While theory predicts that co-infection favours more virulent parasite genotypes through intensified competition for host resources, knowledge of the effects of genotype by genotype (G * G) interactions between unrelated parasite species on virulence of co-infection is limited. Here, we tested such a relationship by challenging rainbow trout with replicated bacterial strains and fluke genotypes both singly and in all possible pairwise combinations. We found that virulence (host mortality) was higher in co-infections compared with single infections. Importantly, we also found that the overall virulence was dependent on the genetic identity of the co-infecting partners so that the outcome of co-infection could not be predicted from the respective virulence of single infections. Our results imply that G * G interactions among co-infecting parasites may significantly affect host health, add to variance in parasite fitness and thus influence evolutionary dynamics and ecology of disease in unexpected ways. PMID- 26674951 TI - Sustained fitness gains and variability in fitness trajectories in the long-term evolution experiment with Escherichia coli. AB - Many populations live in environments subject to frequent biotic and abiotic changes. Nonetheless, it is interesting to ask whether an evolving population's mean fitness can increase indefinitely, and potentially without any limit, even in a constant environment. A recent study showed that fitness trajectories of Escherichia coli populations over 50 000 generations were better described by a power-law model than by a hyperbolic model. According to the power-law model, the rate of fitness gain declines over time but fitness has no upper limit, whereas the hyperbolic model implies a hard limit. Here, we examine whether the previously estimated power-law model predicts the fitness trajectory for an additional 10 000 generations. To that end, we conducted more than 1100 new competitive fitness assays. Consistent with the previous study, the power-law model fits the new data better than the hyperbolic model. We also analysed the variability in fitness among populations, finding subtle, but significant, heterogeneity in mean fitness. Some, but not all, of this variation reflects differences in mutation rate that evolved over time. Taken together, our results imply that both adaptation and divergence can continue indefinitely--or at least for a long time--even in a constant environment. PMID- 26674952 TI - The hyoid arch and braincase anatomy of Acanthodes support chondrichthyan affinity of 'acanthodians'. AB - Solving the evolutionary relationships of the acanthodians is one of the key problems in reconstructing ancestral anatomical conditions for the jawed vertebrates (gnathostomes). Current debate concerns whether acanthodians are an assemblage of stem chondrichthyans, or a more generalized grade encompassing some early stem osteichthyans. The skull anatomy of Acanthodes bronni has been pivotal in these debates, owing to tension between chondrichthyan- and osteichthyan-like models of reconstruction. We use computed tomography scanning and traditional palaeontological techniques to resolve the long-standing debate about the anatomy of the jaw suspension. We establish the correct length of the hyomandibula and show that it attaches to a process on the ventrolateral angle of the braincase below the jugular vein groove. This condition corresponds precisely to that in chondrichthyans. This character represents an unambiguously optimized synapomorphy with chondrichthyans given current gnathostome phylogenies, corroborating the growing consensus of the chondrichthyan affinity of acanthodians. PMID- 26674953 TI - A horizontally transferred nuclear gene is associated with microhabitat variation in a natural plant population. AB - Horizontal gene transfer involves the non-sexual interspecific transmission of genetic material. Even if they are initially functional, horizontally transferred genes are expected to deteriorate into non-expressed pseudogenes, unless they become adaptively relevant in the recipient organism. However, little is known about the distributions of natural transgenes within wild species or the adaptive significance of natural transgenes within wild populations. Here, we examine the distribution of a natural plant-to-plant nuclear transgene in relation to environmental variation within a wild population. Festuca ovina is polymorphic for an extra (second) expressed copy of the nuclear gene (PgiC) encoding cytosolic phosphoglucose isomerase, with the extra PgiC locus having been acquired horizontally from the distantly related grass genus Poa. We investigated variation at PgiC in samples of F. ovina from a fine-scale, repeating patchwork of grassland microhabitats, replicated within spatially separated sites. Even after accounting for spatial effects, the distributions of F. ovina individuals carrying the additional PgiC locus, and one of the enzyme products encoded by the locus, are significantly associated with fine-scale habitat variation. Our results suggest that the PgiC transgene contributes, together with the unlinked 'native' PgiC locus, to local adaptation to a fine-scale mosaic of edaphic and biotic grassland microhabitats. PMID- 26674954 TI - Are flies kind to kin? The role of intra- and inter-sexual relatedness in mediating reproductive conflict. AB - As individual success often comes at the expense of others, interactions between the members of a species are frequently antagonistic, especially in the context of reproduction. In theory, this conflict may be reduced in magnitude when kin interact, as cooperative behaviour between relatives can result in increased inclusive fitness. Recent tests of the potential role of cooperative behaviour between brothers in Drosophila melanogaster have proved to be both exciting and controversial. We set out to replicate these experiments, which have profound implications for the study of kin selection and sexual conflict, and to expand upon them by also examining the potential role of kinship between males and females in reproductive interactions. While we did observe reduced fighting and courtship effort between competing brothers, contrary to previous studies we did not detect any fitness benefit to females as a result of the modification of male antagonistic behaviours. Furthermore, we did not observe any differential treatment of females by their brothers, as would be expected if the intensity of sexual conflict was mediated by kin selection. In the light of these results, we propose an alternative explanation for observed differences in male-male conflict and provide preliminary empirical support for this hypothesis. PMID- 26674955 TI - Investigating the genetic architecture of conditional strategies using the environmental threshold model. AB - The threshold expression of dichotomous phenotypes that are environmentally cued or induced comprise the vast majority of phenotypic dimorphisms in colour, morphology, behaviour and life history. Modelled as conditional strategies under the framework of evolutionary game theory, the quantitative genetic basis of these traits is a challenge to estimate. The challenge exists firstly because the phenotypic expression of the trait is dichotomous and secondly because the apparent environmental cue is separate from the biological signal pathway that induces the switch between phenotypes. It is the cryptic variation underlying the translation of cue to phenotype that we address here. With a 'half-sib common environment' and a 'family-level split environment' experiment, we examine the environmental and genetic influences that underlie male dimorphism in the earwig Forficula auricularia. From the conceptual framework of the latent environmental threshold (LET) model, we use pedigree information to dissect the genetic architecture of the threshold expression of forceps length. We investigate for the first time the strength of the correlation between observable and cryptic 'proximate' cues. Furthermore, in support of the environmental threshold model, we found no evidence for a genetic correlation between cue and the threshold between phenotypes. Our results show strong correlations between observable and proximate cues and less genetic variation for thresholds than previous studies have suggested. We discuss the importance of generating better estimates of the genetic variation for thresholds when investigating the genetic architecture and heritability of threshold traits. By investigating genetic architecture by means of the LET model, our study supports several key evolutionary ideas related to conditional strategies and improves our understanding of environmentally cued decisions. PMID- 26674956 TI - Evidence for carry-over effects of predator exposure on pathogen transmission potential. AB - Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite Plasmodium falciparum, the mosquito vector Anopheles coluzzii and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to P. falciparum, it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology. PMID- 26674957 TI - Disintegration of Carbon Dioxide Molecules in a Microwave Plasma Torch. AB - A pure carbon dioxide torch is generated by making use of 2.45 GHz microwave. Carbon dioxide gas becomes the working gas and produces a stable carbon dioxide torch. The torch volume is almost linearly proportional to the microwave power. Temperature of the torch flame is measured by making use of optical spectroscopy and thermocouple. Two distinctive regions are exhibited, a bright, whitish region of high-temperature zone and a bluish, dimmer region of relatively low temperature zone. Study of carbon dioxide disintegration and gas temperature effects on the molecular fraction characteristics in the carbon dioxide plasma of a microwave plasma torch under atmospheric pressure is carried out. An analytical investigation of carbon dioxide disintegration indicates that substantial fraction of carbon dioxide molecules disintegrate and form other compounds in the torch. For example, the normalized particle densities at center of plasma are given by nCO2/nN = 6.12 * 10(-3), nCO/nN = 0.13, nC/nN = 0.24, nO/nN = 0.61, nC2/nN = 8.32 * 10(-7), nO2/nN = 5.39 * 10(-5), where nCO2, nCO, nC, nO, nC2, and nO2 are carbon dioxide, carbon monoxide, carbon and oxygen atom, carbon and oxygen molecule densities, respectively. nN is the neutral particle density. Emission profiles of the oxygen and carbon atom radicals and the carbon monoxide molecules confirm the theoretical predictions of carbon dioxide disintegration in the torch. PMID- 26674958 TI - Diagnosis of Helicobacter Pylori Infection is Associated with Lower Prevalence and Subsequent Incidence of Crohn's Disease. AB - BACKGROUND AND AIMS: Helicobacter pylori infection may protect against some chronic inflammatory diseases. This study examined H. pylori infection and its association with the prevalence of the gastrointestinal diseases Crohn's disease [CD], ulcerative colitis [UC], and coeliac disease [CeD]. Incident cases in a follow-up period after H. pylori testing were recorded to investigate if protective effects of H. pylori persisted after probable eradication. METHODS: This was a historical cohort study performed in the Central Denmark Region. Patients were enrolled consecutively from primary health care centres after a urea breath test [UBT] for H. pylori and were then followed for a median of 6 years. The patient's diseases, country of birth, and gender were acquired from nationwide administrative registries. We used logistic regression to compare the prevalences of CD, UC, and CeD and Cox regression to compare the incidences of CD, UC, and CeD between H. pylori-positive and H. pylori-negative patients, adjusting for confounding variables. RESULTS: We found a lower prevalence of CD in H. pylori-positive than in H. pylori-negative patients (odds ratio = 0.36 [0.17-0.75]). There were fewer incident cases of CD in H. pylori-positive than H. pylori-negative patients in the follow-up period (hazard ratio = 0.59 [0.36 0.96]). Similar trends were found for CeD but not for UC. CONCLUSIONS: H. pylori infection may be a protective factor against the development of CD. However, the incidence of CD is still reduced after UBT and probable H. pylori eradication; thus, H. pylori status may be a marker for other factors that protect against CD. PMID- 26674959 TI - Modified Side-To-Side Isoperistaltic Strictureplasty over the Ileocaecal Valve: An Alternative to Ileocaecal Resection in Extensive Terminal Ileal Crohn's Disease. AB - BACKGROUND: A modified Michelassi strictureplasty over the ileocaecal valve or ileocolic anastomosis could be an alternative to ileocaecal resection. This study assessed the outcome of the modified Michelassi strictureplasty in patients with extensive stenotic terminal ileal Crohn's disease [CD]. METHODS: This type of strictureplasty was proposed to all patients with an extensive strictured [neo-] terminal ileal segment [> 20 cm]. Short- and long-term outcome data were retrieved from a prospectively maintained database. Safety and medium-term efficacy were studied, using both postoperative magnetic resonance enterography [MRE] and ileocolonoscopy at 6 months. RESULTS: Between June 2009 and September 2014, 29 CD patients had a modified strictureplasty [male 9/29, median age 38 [range: 16-64] years]. The median length of strictureplasty was 50 [27-110] cm. Twelve patients underwent a total of 30 additional procedures during surgery, mainly additional short strictureplasties, but also segmental resections. The majority had a laparoscopic-assisted procedure. Median length of hospital stay was 9 [6-17] days. Two patients had an early rescue procedure to oversew a small anastomotic leak. MRE and ileocolonoscopy at follow-up showed a remarkable regression of inflammation and bowel wall thickness. Clinical recurrence, necessitating initiation or modification of medical therapy, and surgical recurrence were reported in 11 and 1 patient after a median follow-up of 21 [1 54] months, respectively. CONCLUSION: A modified long Michelassi strictureplasty appears to be safe in patients with extensive stricturing Crohn's ileitis. Significant mucosal and bowel wall healing is observed and suggests that clearance of microbial stasis may play a role in this process. PMID- 26674960 TI - Assessment of the utility of ultrasonography with high-frequency transducers in the diagnosis of postoperative neuropathies. AB - The primary aim of this paper was to assess the relevance of high-frequency ultrasound examination in qualifying patients for either surgical or conservative treatment of postoperative peripheral neuropathies. The study was conducted in a group of 71 patients who in 2009-2011 were referred to ultrasound examinations due to a clinical suspicion of peripheral neuropathies. For the purposes of this analysis, the suspected postoperative neuropathies were divided into three groups: after surgical treatment of the median nerve (1), after surgical treatment of the ulnar nerve (2) and other postoperative neuropathies (3). All patients underwent the interview, physical examination and ultrasound examination. The ultrasound examinations were performed with Esaote MyLab 50 and MyLab 60 systems. Based on the clinical and US examinations, the patients were qualified for either surgical (51 cases) or conservative treatment (20 cases). An EMG examination was also performed in certain patients (60 cases). Mean values of cross-sectional areas and diameters of the nerve trunks were calculated in individual pathology groups. The ultrasound features of the peripheral nerves analyzed in the study, such as echostructure, notch sign, hyperemia and continuity of the transverse ligament, were divided into subgroups. Moreover, the frequency of adhesions between the nerve trunks and adjacent tissues, occurrence of pain on compression with a transducer and instability of the ulnar nerve as well as angulation of the posterior interosseous nerve in a dynamic examination was calculated. The analyses of the collected material were performed by means of descriptive statistics. The results of clinical and surgical verification were consistent with ultrasound findings in 100% of cases. The results indicate that high-frequency ultrasonography is a valuable method in qualifying patients for various types of treatment of peripheral postoperative neuropathies. PMID- 26674962 TI - Editorial Comment on: U. Zaleska-Dorobisz, A. Biel, D. Sokolowska-Dabek, C. Olchowy, M. Lasecki Ultrasonography in the diagnosis of hemorrhagic cystitis - a complication of bone marrow transplantation in pediatric oncology patients. PMID- 26674961 TI - Decreased PCSK9 expression in human hepatocellular carcinoma. AB - BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC. PMID- 26674963 TI - Characterization of Ca(2+)-Dependent Protein-Protein Interactions within the Ca(2+) Release Units of Cardiac Sarcoplasmic Reticulum. AB - In the heart, excitation-contraction (E-C) coupling is mediated by Ca(2+) release from sarcoplasmic reticulum (SR) through the interactions of proteins forming the Ca(2+) release unit (CRU). Among them, calsequestrin (CSQ) and histidine-rich Ca(2+) binding protein (HRC) are known to bind the charged luminal region of triadin (TRN) and thus directly or indirectly regulate ryanodine receptor 2 (RyR2) activity. However, the mechanisms of CSQ and HRC mediated regulation of RyR2 activity through TRN have remained unclear. We first examined the minimal KEKE motif of TRN involved in the interactions with CSQ2, HRC and RyR2 using TRN deletion mutants and in vitro binding assays. The results showed that CSQ2, HRC and RyR2 share the same KEKE motif region on the distal part of TRN (aa 202-231). Second, in vitro binding assays were conducted to examine the Ca(2+) dependence of protein-protein interactions (PPI). The results showed that TRN-HRC interaction had a bell-shaped Ca(2+) dependence, which peaked at pCa4, whereas TRN-CSQ2 or TRN-RyR2 interaction did not show such Ca(2+) dependence pattern. Third, competitive binding was conducted to examine whether CSQ2, HRC, or RyR2 affects the TRN-HRC or TRN-CSQ2 binding at pCa4. Among them, only CSQ2 or RyR2 competitively inhibited TRN-HRC binding, suggesting that HRC can confer functional refractoriness to CRU, which could be beneficial for reloading of Ca(2+) into SR at intermediate Ca(2+) concentrations. PMID- 26674964 TI - Estrogen Receptor alpha Regulates Dlx3-Mediated Osteoblast Differentiation. AB - Estrogen receptor alpha (ER-alpha), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER alpha in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-alpha is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-alpha interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-alpha is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-alpha, and that ER-alpha regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3. PMID- 26674965 TI - Over-Expression of Ephrin-A5 in Mice Results in Decreasing the Size of Progenitor Pool through Inducing Apoptosis. AB - Eph receptors and their ligands, ephrins, mediate cell-to-cell contacts in a specific brain region and their bidirectional signaling is implicated in the regulation of apoptosis during early brain development. In this report, we used the alpha(alpha)-Cre transgenic line to induce ephrin-A5 over-expression in the distal region of the neural retina. Using this double transgenic embryo, we show that the over-expression of ephrin-A5 was responsible for inducing massive apoptosis in both the nasal and temporal retinas. In addition, the number of differentiated retinal neurons with the exception of the bipolar neuron was significantly reduced, whereas the laminar organization of the mature retina remained intact. Consistent with this finding, an analysis of the mature retina revealed that the size of the whole retina--particularly the nasal and temporal regions--is markedly reduced. These results strongly suggest that the level of ephrin-A5 expression plays a role in the regulation of the size of the retinal progenitor pool in the neural retina. PMID- 26674966 TI - CaPUB1, a Hot Pepper U-box E3 Ubiquitin Ligase, Confers Enhanced Cold Stress Tolerance and Decreased Drought Stress Tolerance in Transgenic Rice (Oryza sativa L.). AB - Abiotic stresses such as drought and low temperature critically restrict plant growth, reproduction, and productivity. Higher plants have developed various defense strategies against these unfavorable conditions. CaPUB1 (Capsicum annuum Putative U-box protein 1) is a hot pepper U-box E3 Ub ligase. Transgenic Arabidopsis plants that constitutively expressed CaPUB1 exhibited drought sensitive phenotypes, suggesting that it functions as a negative regulator of the drought stress response. In this study, CaPUB1 was over-expressed in rice (Oryza sativa L.), and the phenotypic properties of transgenic rice plants were examined in terms of their drought and cold stress tolerance. Ubi:CaPUB1 T3 transgenic rice plants displayed phenotypes hypersensitive to dehydration, suggesting that its role in the negative regulation of drought stress response is conserved in dicot Arabidopsis and monocot rice plants. In contrast, Ubi:CaPUB1 progeny exhibited phenotypes markedly tolerant to prolonged low temperature (4 degrees C) treatment, compared to those of wild-type plants, as determined by survival rates, electrolyte leakage, and total chlorophyll content. Cold stress-induced marker genes, including DREB1A, DREB1B, DREB1C, and Cytochrome P450, were more up regulated by cold treatment in Ubi:CaPUB1 plants than in wild-type plants. These results suggest that CaPUB1 serves as both a negative regulator of the drought stress response and a positive regulator of the cold stress response in transgenic rice plants. This raises the possibility that CaPUB1 participates in the cross-talk between drought and low-temperature signaling pathways. PMID- 26674967 TI - Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway. AB - Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-3beta activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy. PMID- 26674969 TI - Leaching lithium from the anode electrode materials of spent lithium-ion batteries by hydrochloric acid (HCl). AB - Spent lithium-ion batteries (LIBs) are considered as an important secondary resource for its high contents of valuable components, such as lithium and cobalt. Currently, studies mainly focus on the recycling of cathode electrodes. There are few studies concentrating on the recovery of anode electrodes. In this work, based on the analysis result of high amount of lithium contained in the anode electrode, the acid leaching process was applied to recycle lithium from anode electrodes of spent LIBs. Hydrochloric acid was introduced as leaching reagent, and hydrogen peroxide as reducing agent. Within the range of experiment performed, hydrogen peroxide was found to have little effect on lithium leaching process. The highest leaching recovery of 99.4wt% Li was obtained at leaching temperature of 80 degrees C, 3M hydrochloric acid and S/L ratio of 1:50g/ml for 90min. The graphite configuration with a better crystal structure obtained after the leaching process can also be recycled. PMID- 26674968 TI - A Role for Arabidopsis miR399f in Salt, Drought, and ABA Signaling. AB - MiR399f plays a crucial role in maintaining phosphate homeostasis in Arabidopsis thaliana. Under phosphate starvation conditions, AtMYB2, which plays a role in plant salt and drought stress responses, directly regulates the expression of miR399f. In this study, we found that miR399f also participates in plant responses to abscisic acid (ABA), and to abiotic stresses including salt and drought. Salt and ABA treatment induced the expression of miR399f, as confirmed by histochemical analysis of promoter-GUS fusions. Transgenic Arabidopsis plants overexpressing miR399f (miR399f-OE) exhibited enhanced tolerance to salt stress and exogenous ABA, but hypersensitivity to drought. Our in silico analysis identified ABF3 and CSP41b as putative target genes of miR399f, and expression analysis revealed that mRNA levels of ABF3 and CSP41b decreased remarkably in miR399f-OE plants under salt stress and in response to treatment with ABA. Moreover, we showed that activation of stress-responsive gene expression in response to salt stress and ABA treatment was impaired in miR399f-OE plants. Thus, these results suggested that in addition to phosphate starvation signaling, miR399f might also modulates plant responses to salt, ABA, and drought, by regulating the expression of newly discovered target genes such as ABF3 and CSP41b. PMID- 26674970 TI - Copper(I) complexes with phosphine derived from sparfloxacin. Part II: a first insight into the cytotoxic action mode. AB - In this paper we present a first insight into the cytotoxic action mode of copper(I) iodide or copper(I) thiocyanate complexes with a phosphine derivative of sparfloxacin (a 3rd generation fluoroquinolone antibiotic agent) and 2,9 dimethyl-1,10-phenanthroline or 2,2'-biquinoline as auxiliary ligands. The in vitro cytotoxic activity of the new complexes was tested against two cancer cell lines (CT26--mouse colon carcinoma and A549--human lung adenocarcinoma). An ICP MS study revealed a marked time-dependent intracellular copper accumulation of the tested compounds. In addition, confocal microscopy imaging showed accumulation of the complexes inside whole cells and their emission of blue light. The complexes generate reactive oxygen species in the cancer cells, which was examined by using two different fluorescent probes. Moreover, (I) DNA intercalation studied by luminescence spectroscopy, circular dichroism and molecular docking, and (II) plasmid DNA damage also demonstrate their significant cytotoxicity. All these observed biological effects contribute to the induction of apoptosis, observed at a great predominance. PMID- 26674971 TI - A novel relational regularization feature selection method for joint regression and classification in AD diagnosis. AB - In this paper, we focus on joint regression and classification for Alzheimer's disease diagnosis and propose a new feature selection method by embedding the relational information inherent in the observations into a sparse multi-task learning framework. Specifically, the relational information includes three kinds of relationships (such as feature-feature relation, response-response relation, and sample-sample relation), for preserving three kinds of the similarity, such as for the features, the response variables, and the samples, respectively. To conduct feature selection, we first formulate the objective function by imposing these three relational characteristics along with an l2,1-norm regularization term, and further propose a computationally efficient algorithm to optimize the proposed objective function. With the dimension-reduced data, we train two support vector regression models to predict the clinical scores of ADAS-Cog and MMSE, respectively, and also a support vector classification model to determine the clinical label. We conducted extensive experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to validate the effectiveness of the proposed method. Our experimental results showed the efficacy of the proposed method in enhancing the performances of both clinical scores prediction and disease status identification, compared to the state-of-the-art methods. PMID- 26674973 TI - Polymorphisms in IL-10 and INF-gamma genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults. AB - Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103) and carotid arteries (CA, n = 66) of autopsied young adults (< 30 years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-alpha (- 308G/A and - 238 G/A), IFN-gamma (+ 874 A/T), MMP-9 (- 1562 C/T), IL-10 (- 1082 A/G and - 819 C/T), NOS3 (894 G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-beta (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-gamma and IL-10 (- 1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-gamma (p < 0.001) and IL-10 (p = 0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification. PMID- 26674972 TI - On characterizing population commonalities and subject variations in brain networks. AB - Brain networks based on resting state connectivity as well as inter-regional anatomical pathways obtained using diffusion imaging have provided insight into pathology and development. Such work has underscored the need for methods that can extract sub-networks that can accurately capture the connectivity patterns of the underlying population while simultaneously describing the variation of sub networks at the subject level. We have designed a multi-layer graph clustering method that extracts clusters of nodes, called 'network hubs', which display higher levels of connectivity within the cluster than to the rest of the brain. The method determines an atlas of network hubs that describes the population, as well as weights that characterize subject-wise variation in terms of within- and between-hub connectivity. This lowers the dimensionality of brain networks, thereby providing a representation amenable to statistical analyses. The applicability of the proposed technique is demonstrated by extracting an atlas of network hubs for a population of typically developing controls (TDCs) as well as children with autism spectrum disorder (ASD), and using the structural and functional networks of a population to determine the subject-level variation of these hubs and their inter-connectivity. These hubs are then used to compare ASD and TDCs. Our method is generalizable to any population whose connectivity (structural or functional) can be captured via non-negative network graphs. PMID- 26674975 TI - The resurgence of indefiniteness? PMID- 26674974 TI - Cytokeratin 20 positive circulating tumor cells are a marker for response after neoadjuvant chemoradiation but not for prognosis in patients with rectal cancer. AB - BACKGROUND: Several studies have shown, that circulating tumor cells (CTC) have a negative prognostic value in colorectal cancer patients. Aim of this study was to evaluate the role of CTC in specifically rectal cancer patients regarding the influence on overall survival and to elucidate the impact of CTC in predicting response after chemoradiation (RCTX). METHODS: In this prospective monocentric study 267 patients with rectal cancer were included. Patients with locally advanced tumors were treated with RCTX followed by surgery. The primary endpoints were: Evaluation of CTC at the time of surgery and correlation with main tumor characteristics, response to neoadjuvant RCTX and overall survival (OS). CTC were detected in the blood using CK20 RT-PCR. RESULTS: Sixty-three patients were treated with neoadjuvant RCTX. In 46.8% of the patients receiving neoadjuvant RCTX CTC were detected, which was significantly higher than in the group without RCTX (p=0.002). Histopathologic regression after RCTX was evident in 27.8% of the patients. In the subgroup of responders after RCTX we found CTC at a significantly lower rate than in non-responders (p=0.03). No significant association was found between CTC detection and tumor characteristics and OS. The OS was significantly improved for responders compared to non-responders (p=0.007). CONCLUSIONS: Responders after neoadjuvant RCTX had a lower incidence of CTC compared to non-responders, which might be a result of effective systemic and local treatment prior to surgery. Interestingly, detection of CTC did not correlate with tumor stage and OS, which is in contrast to previous reports of patients with colon cancer. PMID- 26674976 TI - Bacterial Exopolysaccharide of Shallow Marine Vent Origin as Agent in Counteracting Immune Disorders Induced by Herpes Virus. AB - Herpes simplex virus type 2 (HSV-2) is responsible of the continuously increasing viral infections in humans. In a previous study we demonstrated that the exopolysaccharide produced by Bacillus licheniformis strain B3-15 (EPS-B3-15), was able to hinder the HSV-2 replication in peripheral blood mononuclear cells (PBMC) and this antiviral activity appear to be related to a significant stimulation of the Th1-cytokines. In this study we analyse the role of EPS-B3-15 on Th2 cytokine production by PBMC infected or not with HSV-2. EPS-B3-15 demonstrate the ability to induce a particular cytokine network with consequent effects on the immune cells during HSV-2 infection. PMID- 26674977 TI - Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir. AB - BACKGROUND/AIMS: We aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on viral kinetics and virologic response to tenofovir and entecavir treatment in patients with chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: This study was designed as a retrospective multicenter cohort study. The impact of hepatosteatosis on pre-treatment serum HBV DNA levels and also on the virologic response to either tenofovir or entecavir at 6 and 12 months of therapy was investigated. RESULTS: A total of 145 cases were involved in the study [median age 40 (18-73) years, 90 (62%) males]. In multivariate analysis, it was detected that patients with NAFLD were older and had a higher body mass index (BMI) [Odds ratio (95% confidence interval) and p-value for age were 1.040 (1.003-1.079) and 0.033 and for BMI were 1.348 (1.190-1.528) and 0.0001, respectively]. When only the 43 patients who were younger than 35.5 years old and who had a BMI less than 27.59 were investigated, serum high-density lipoprotein (HDL) levels and serum HBV DNA levels were lower in patients with NAFLD in multivariate analysis [Odds ratio (95% confidence interval) and p-values for serum HDL level and HBV DNA level were 0.864 (0.061-0.980) and 0.023 and 0.995 (0.990-0.999) and 0.025, respectively]. Totally, 57 and 75 of the patients had received entecavir and tenofovir, respectively. CONCLUSION: Viral replication decreases in patients with chronic HBV infection in the presence of NAFLD, and NAFLD had no impact on the virologic response to entecavir and tenofovir treatment. PMID- 26674978 TI - Effectiveness and safety of biliary stenting in the management of difficult common bile duct stones in elderly patients. AB - BACKGROUND/AIMS: To investigate the efficacy and safety of endoscopic biliary stenting for difficult common bile duct (CBD) stones in elderly patients. MATERIALS AND METHODS: Elderly patients (>=65 years) with large (>=20 mm) or multiple (>=3) CBD stones were studied. The patients underwent placement of single (n=34, group A) or double (n=30, group B) plastic stents at the time of initial endoscopic retrograde cholangiopancreatography (ERCP). Approximately 3 months later, stone removal was attempted at the second ERCP. The reduction of stone size and number before and after biliary stenting, complete stone removal, 3-month stent patency rate, and complications were compared. RESULTS: The mean size (longitudinal/transverse diameter) of the CBD stones was significantly reduced after biliary stenting in both groups (p<0.001). Complete stone removal at the second ERCP was 94.1% in group A and 100% in group B (p=0.494). Kaplan Meier analysis indicated that group B had a higher 3-month stent patency rate than group A (p=0.008). CONCLUSION: Endoscopic biliary stenting is safe and feasible for the management of difficult CBD stones in elderly patients, while double biliary stenting is superior to single stenting in maintaining higher stent patency rates. PMID- 26674979 TI - Changes in pressure waves after endoscopic intervention in patients with achalasia: A focus on peristaltic recovery of the esophageal body. AB - BACKGROUND/AIMS: We conducted the present study to investigate the recovery of peristalsis of the esophageal body and evaluate the pressure changes observed on manometry before and after endoscopic intervention. MATERIALS AND METHODS: Forty five patients were diagnosed with achalasia, and 36 received endoscopic or surgical treatment. We collected the data of 24 patients who underwent manometry before and after treatment (pneumatic balloon dilatation, n=7; botulinum toxin injection, n=10; peroral endoscopic myotomy, n=7). RESULTS: The lower esophageal sphincter (LES) resting pressure and nadir LES relaxation pressure decreased regardless of the achalasia subtype or type of endoscopic intervention following treatment (p<0.05). Among patients with a nadir LES relaxation pressure of <4 mmHg, 42.9% (6/14) exhibited partial esophageal peristaltic wave recovery. However, no patients with a nadir LES relaxation pressure of >4 mmHg exhibited peristaltic wave recovery (p=0.024). Of the six patients with peristaltic wave recovery, two had type I achalasia (15.4%), three had type II (33.3%), and one had type III (100.0%). The Eckardt score, symptom duration, and type of intervention were not associated with the recovery of peristaltic waves. CONCLUSION: Our results suggest that normalization of the nadir LES relaxation pressure can be a predictive factor for the recovery of esophageal peristalsis. PMID- 26674980 TI - A systematic review of the prevalence and risk factors of irritable bowel syndrome among medical students. AB - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) represents a great challenge to public health, particularly among medical students. The aim of the study was to determine the global prevalence and risk factors of IBS among medical students. MATERIALS AND METHODS: Data were obtained through searches in PubMed, Ovid, the Cochrane database, Embase, Google scholar, Institute for Scientific Information (ISI) "Web of Science," and Medline from 1990 to June 2015. The search terms included "Irritable Bowel Syndrome" and "Medical students" and "prevalence, risk factors". More than 100 articles were reviewed, scrutinized, and critically appraised for the eligibility criteria, and the relevant articles were selected. RESULTS: Sixteen studies were identified, and the prevalence of IBS among medical students ranged from 9.3% to 35.5%. The relatively high prevalence among medical students may be attributed to their special stressful learning environment. Some studies found that female gender, family history of IBS, psychiatric stress, anxiety, depression, infections, dietary factors, and sleep disorders were associated with IBS. CONCLUSION: A relatively high prevalence of IBS was prevalent among medical students. Annual screening of IBS and introduction of stress management courses are recommended. PMID- 26674981 TI - Post-colonoscopy colorectal cancers in average-risk Korean subjects with a normal initial colonoscopy. AB - BACKGROUND/AIMS: There are relatively few studies regarding the incidence of post colonoscopy colorectal cancer (PCCRC) in Asian countries. We evaluated the characteristics of PCCRC in average-risk Korean subjects. MATERIALS AND METHODS: This study included subjects who were >=50 years of age and had undergone a first completed colonoscopy between January 2001 and December 2004, at which no baseline adenoma had been detected, followed by a second colonoscopy 1-5 years later. The incidences and characteristics of advanced neoplasia in these subjects were assessed. RESULTS: A total of 343 subjects underwent follow-up colonoscopy within 5 years. Seventy-three (21.3%) subjects were found to have at least one adenoma on follow-up colonoscopy. Advanced adenoma was found in eight (2.3%) subjects, and non-advanced adenomas were found in 65 (19.0%). Five (1.5%) subjects were diagnosed with invasive CRC following a normal colonoscopy. The putative reason for PCCRCs was missed lesions in two (40.0%) subjects and a new cancer in three (60.0%). CONCLUSION: The risk of advanced neoplasia (including PCCRCs) within 5 years after a normal baseline colonoscopy in our cohort was not low. Considering that 40% of PCCRCs were attributable to missed lesions, our results emphasize the need for technical improvement of colonoscopic examinations to improve adenoma detection. PMID- 26674982 TI - Can eicosapentaenoic acid maintain the original ribavirin dose or affect the response during the treatment course of chronic hepatitis C virus (HCV) patients? AB - BACKGROUND/AIMS: Combination therapy with peginterferon (PEG-IFN) and ribavirin (RBV) has been recommended as a standard therapy for patients with chronic hepatitis C virus (HCV). Our aim was to evaluate the efficacy of eicosapentaenoic acid (EPA) against RBV-associated hemolytic anemia. MATERIALS AND METHODS: Two hundred and forty HCV patients included in the study were randomized to either the EPA group (n=120) or non-EPA group (n=120), and they received combination therapy with or without EPA. We compare changes in hemoglobin levels with RBV dose reduction rate in each group as well as treatment response. RESULTS: Of 120 patients randomized to receive combination therapy with EPA, 15/86 (17.5%) patients required RBV dose reduction, whereas 71/86 (82.5%) patients did not require RBV dose reduction; in the non-EPA group, 22/80 (27.5%) patients required RBV dose reduction and 58/80 (72.5%) patients did not require RBV dose reduction. There was no significant difference between the two groups in the rates of virologic response. CONCLUSION: EPA can decrease the rate of RBV dose reduction and RBV-induced hemolysis during the course of combination treatment. Further trials are required to investigate the role of EPA in the current regimens of HCV treatment that include ribavirin. PMID- 26674983 TI - A case for the use of receiver operating characteristic analysis of potential clinical efficacy biomarkers in advanced renal cell carcinoma. AB - AIM: Assess patient-level utility of suggested pretreatment biomarkers of sunitinib in advanced renal cell carcinoma. PATIENTS & METHODS: Kaplan-Meier analysis of data from a randomized, Phase II study (n = 292) suggested baseline predictive value for circulating soluble Ang-2 and MMP-2 and HIF-1alpha percentage of tumor expression. Using this dataset, the sensitivity, specificity and area under the curve (AUC) were calculated, using receiver operating characteristic (ROC) curves. RESULTS: Based on a ROC (sensitivity vs 1 - specificity) threshold AUC value of >0.8, neither Ang-2 (0.67) nor MMP-2 (0.65), nor HIF-1alpha percentage of tumor expression (0.65), performed appropriately from a patient-selection standpoint. CONCLUSION: To properly assess potential biomarkers, sensitivity and specificity characteristics should be obtained by ROC analysis. PMID- 26674984 TI - Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments. AB - The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (>= 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments. PMID- 26674985 TI - The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARgamma dependent PTEN expression. AB - Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARgamma and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARgamma dependent PTEN/p-Akt expression in the granulosa cells. PMID- 26674986 TI - Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure. AB - OBJECTIVE: We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF). METHODS: Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range (AHRR; calculated as maximum minus minimum heart rate using 24 h Holter monitor data, including paced and non-sinus complexes) in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction. RESULTS: After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (R(2)=0.2; p<0.001) and with peak exercise-test heart rate (R(2)=0.33; p<0.001). Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode specific death as described in the derivation cohort. CONCLUSIONS: AHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity. PMID- 26674988 TI - From comorbidities to heart failure with preserved ejection fraction: a story of oxidative stress. PMID- 26674987 TI - Reducing myocardial infarct size: challenges and future opportunities. AB - Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is 'myocardial reperfusion injury', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. PMID- 26674989 TI - Roadmap for biomarkers of cancer therapy cardiotoxicity. AB - Contemporary cancer treatment uses multiple modalities such as chemotherapy, targeted therapy and radiotherapy. These therapies, often used in combination, are associated with an increased risk of cardiotoxicity, specifically cardiomyopathy and heart failure. Cardiologists and oncologists are faced with the challenge of maximising the clinical benefit from cancer therapy while minimising the risk of early and late-onset cardiotoxicity. The current paradigm for cardiotoxicity detection and management relies primarily upon the assessment of left ventricular ejection fraction (LVEF). However, LVEF alone is limited in both diagnostic and prognostic ability. There is growing enthusiasm over the identification of newer biomarkers of cardiotoxicity that can detect cardiac injury at earlier stages of disease and could be used as an adjunctive prognostic measure to routine LVEF assessment. Thus, imaging and circulating biomarkers are currently under active investigation for use throughout the continuum of cancer care-for risk stratification of cardiotoxicity prior to treatment, detection of early cardiotoxicity during treatment and diagnosis of late cardiotoxicity in survivorship. Myocardial strain, cardiac troponin and brain natriuretic peptide are the most prominent biomarkers currently being studied, although data on novel circulating biomarkers are emerging. PMID- 26674990 TI - PBS machine interlocks using EWMA. AB - Delivery of pencil beam scanning (PBS) requires the on-line measurement of several beam parameters. If the measurement is outside of specified tolerances and a binary threshold algorithm is used, the beam will be paused. Given instrumentation and statistical noise such a system can lead to many pauses which could increase the treatment time. Statistical quality control methods are typically used on manufacturing lines to monitor a process and give early detection of a gradual problem and stop the process if a deviation is statistically significant. These methods can be used to develop a more intuitive algorithm for (PBS) delivery systems that is robust and safe and leads to decreased treatment times. The Exponentially Weighted Moving Average (EWMA) control scheme monitors deviations in beam properties which are averaged over a specified number of measurements with greater weight applied to the more recent ones. Simulation of an EWMA-style algorithm safely detected shifts in random and systematic delivery errors without false alarms. Binary and EWMA methods can be combined for improved reliability without sacrificing patient safety. In the EWMA method, the mean of a beam property can be related to systematic uncertainties and the standard deviation can be related to random uncertainties. This method allows one to have separate interlock levels for each type of uncertainty and to detect systematic trends. PMID- 26674991 TI - Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD. AB - BACKGROUND: The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown. METHODS: In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity. RESULTS: The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target-disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo. CONCLUSION: This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD. PMID- 26674992 TI - The FAITH Trial: Baseline Characteristics of a Church-based Trial to Improve Blood Pressure Control in Blacks. AB - OBJECTIVE: To describe the baseline characteristics of participants in the Faith based Approaches in the Treatment of Hypertension (FAITH) Trial. DESIGN: FAITH evaluates the effectiveness of a faith-based lifestyle intervention vs health education control on blood pressure (BP) reduction among hypertensive Black adults. SETTING PARTICIPANTS AND MAIN MEASURES: Participants included 373 members of 32 Black churches in New York City. Baseline data collected included participant demographic characteristics, clinical measures (eg, blood pressure), behaviors (eg, diet, physical activity), and psychosocial factors (eg, self efficacy, depressive symptoms). RESULTS: Participants had a mean age of 63.4 +/- 11.9 years and 76% were female. About half completed at least some college (53%), 66% had an income >=$20,000, and 42.2% were retired or on disability. Participants had a mean systolic and diastolic BP of 152.1 +/- 16.8 mm Hg and 86.2 +/- 12.2 mm Hg, respectively, and a mean BMI of 32 kg/m2. Hypertension (HTN) medications were taken by 95% of participants, but most (79.1%) reported non adherence to their regimen. Participants reported consuming 3.4 +/- 2.6 servings of fruits and vegetables and received 30.9% of their energy from fat. About one third (35.9%) reported a low activity level. CONCLUSIONS: Participants in the FAITH trial exhibited several adverse clinical and behavioral characteristics at baseline. Future analyses will evaluate the effectiveness of the faith-based lifestyle intervention on changes in BP and lifestyle behaviors among hypertensive Black adults. PMID- 26674993 TI - Recommendation without experts? Epistemological implications in the development of screening guidelines. AB - Controversies concerning mammographic and cervical cancer screening with HPV-DNA recommendations lead to an analysis of the role played by a knowledge of disease epidemiology, natural history and pathogenesis in producing sound recommendations. This analysis calls into question the decision to exclude experts on the specific topic from guideline and recommendation development because such experts may bring prejudices or even conflicts of interest to the debate. According to this approach, methodology is the only factor that guarantees the soundness of evidence assessment. The assumption underlying such an epistemological point of view is that evidence is "absolute," i.e. not linked to any interpretative model or conjecture. Actually, any form of scientific knowledge includes conjectures, which by definition are not demonstrable, in order to interpret evidence. Even as we assess evidence, we need to select or formulate conjectures that explain most of the evidence available. In order to decide on such conjectures, we require individuals who are familiar with the epidemiology and the aetiology of the disease, as well as with the rationale behind the technologies or interventions proposed. Finally, we need individuals who know the strengths and the weaknesses of alternative conjectures; in other words, we also require content experts. PMID- 26674994 TI - Evaluation of the biphasic calcium composite (BCC), a novel bone cement, in a minipig model of pulmonary embolism. AB - Polymethylmethacrylate (PMMA) bone cement, which is used as a filler material in vertebroplasty, is one of the major sources of pulmonary embolism in patients who have undergone vertebroplasty. In the present study, we established and evaluated two animal models of pulmonary embolism by injecting PMMA or biphasic calcium composite (BCC) bone cement with a negative surface charge. A total of 12 adults and healthy Wuzhishan minipigs were randomly divided into two groups, the PMMA and BBC groups, which received injection of PMMA bone cement and BBC bone cement with a negative surface charge in the circulation system through the pulmonary trunk, respectively, to construct animal models of pulmonary embolism. The hemodynamics, arterial blood gas, and plasma coagulation were compared between these two groups. In addition, morphological changes of the lung were examined using three-dimensional computed tomography. The results showed that both PMMA and BCC injections induced pulmonary embolisms in minipigs. Compared to the PMMA group, the BCC group exhibited significantly lower levels of arterial pressure, pulmonary artery pressure, blood oxygen pressure, blood carbon dioxide pressure, blood bicarbonate, base excess, antithrombin III and D-dimer. In conclusion, BCC bone cement with a negative surface charge is a promising filler material for vertebroplasty. PMID- 26674995 TI - Impact of the electron-phonon coupling symmetry on the polaron stability and mobility in organic molecular semiconductors. AB - The influence of the interplay between symmetric and antisymmetric inter molecular electron-phonon (e-ph) coupling mechanisms on the polaron stability and mobility in organic semiconductors has been theoretically investigated at a molecular level. A semi-empirical Holstein-Peierls model is used which in addition to the symmetric and antisymmetric inter-molecular e-ph interactions also includes an antisymmetric intra-molecular e-ph coupling. Our results show that the symmetric e-ph coupling plays the role of destabilizing the polaron as a result of temperature induced phonons that, via the symmetric coupling, affects the charge distribution of the polaron. Considering this kind of coupling, the parameter space for which the polaron is dynamically stable is strongly temperature-dependent. For the combination of symmetric e-ph coupling strength and temperature, which results in a stable polaron, the velocity of the polaron, and therefore also the charge carrier mobility, is not affected by the symmetric e-ph coupling strength. PMID- 26674996 TI - Immunoregulation at the gliovascular unit in the healthy brain: A focus on Connexin 43. AB - In the brain, immune cell infiltration is normally kept at a very low level and a unique microenvironment strictly restricts immune reactions and inflammation. Even in such quiescent environment, a constant immune surveillance is at work allowing the brain to rapidly react to threats. To date, knowledge about the factors regulating the brain-immune system interrelationship in healthy conditions remains elusive. Interestingly, astrocytes, the most abundant glial cells in the brain, may participate in many aspects of this unique homeostasis, in particular due to their close interaction with the brain vascular system and expression of a specific molecular repertoire. Indeed, astrocytes maintain the blood-brain barrier (BBB) integrity, interact with immune cells, and participate in the regulation of intracerebral liquid movements. We recently showed that Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the BBB interface, is an immunoregulating factor. The absence of astroglial Cx43 leads to a transient endothelial activation, a continuous immune recruitment as well as the development of a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein expressed by astrocytes. In this review, we propose to gather current knowledge on how astrocytes may influence the immune system in the healthy brain, focusing on their roles at the gliovascular interface. We will also consider pathological situations involving astrocyte-specific autoimmunities. Finally, we will discuss the specific role of astroglial Cx43 and the physiological consequences of immune regulations taking place on inflammation, cognition and behavior in the absence of Cx43. PMID- 26674997 TI - Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation. AB - BACKGROUND: In a previous study, we found an up-regulated inflammatory monocyte gene expression profile in major depressive disorder (MDD) patients aged ? 28 years and a down-regulated inflammatory gene expression profile in MDD patients aged<28 years. In the same sample of patients, we aimed to investigate immune dysregulation in the lymphocyte arm of the immune system, particularly in the context of the described monocyte (de-)activation states. METHODS: From deep frozen leukocytes, circulating percentages of monocytes, lymphocytes, B, T, and natural killer (NK) cells, and various functional subsets of T and T helper (Th) cells (Th1, Th2, Th17, and natural T regulatory cells) were measured in N=50 MDD patients and N=58 age- and gender-matched healthy controls (HC). In addition, serum levels of interleukin (IL)-6, sCD25, IL-7, IL-3, SCF, IGF-BP2, and EGF were evaluated. RESULTS: MDD patients were in general characterized by an impaired maturation of Th2 cells, Th17 cells, and NK cells and by decreased serum levels of IL-7 and sCD25. MDD patients aged ? 28 years additionally exhibited decreased percentages of CD4(+)CD25(high)FoxP3(+) T regulatory cells, next to signs of the above described partial T cell defects. Natural T regulatory cells were inversely associated with the pro-inflammatory state of the monocytes (r=-.311; p=.034) that characterized this patient subgroup. CONCLUSIONS: Deficiencies of the NK and T (regulatory) cell system and inflammatory monocyte immune activation co-occur as partly interrelated phenomena within the same MDD patients. PMID- 26674998 TI - Kangaroo care by fathers and mothers: comparison of physiological and stress responses in preterm infants. AB - OBJECTIVE: To compare physiological and biochemical responses in stable preterm neonates and their parents following kangaroo mother care (KMC) and kangaroo father care (KFC). STUDY DESIGN: We conducted a prospective cross-over design study of stable preterm neonates of <35 weeks gestation in a tertiary Neonatal Unit in Toronto. All neonates received KMC and KFC for 1 h on consecutive days in a random order. Heart rate, temperature, blood pressure, oxygen saturation and salivary cortisol in infants before and after kangaroo care and heart rate, temperature and salivary cortisol in parents before and after kangaroo care were measured. Pairwise comparisons of changes in these measures were analyzed. RESULT: Twenty-six sets of neonates and their parents were studied for physiological parameters, of which 19 had adequate samples for salivary cortisol assessment. The infants had a mean birth weight of 1096 g (s.d.=217) and a mean postmenstrual age at study of 32 weeks (s.d.=2). There were no significant differences in the changes in mean heart rate (P=0.51), temperature (P=0.37), oxygen saturation (P=0.50), systolic blood pressure (P=0.32), mean blood pressure (0.10) and salivary cortisol (P=0.50) before and after KMC or KFC in the neonates. The changes in mean heart rate (P=0.62), temperature (P=0.28) and salivary cortisol (P=0.59) before and after kangaroo care were similar between mothers and fathers. CONCLUSION: No significant differences in physiological and stress responses were identified following KMC or KFC in preterm neonates. KFC may be as safe and as effective as KMC. PMID- 26674999 TI - Maturational, comorbid, maternal and discharge domain impact on preterm rehospitalizations: a comparison of planned and unplanned rehospitalizations. AB - OBJECTIVE: To determine the predictive value of (1) maternal, (2) maturational, (3) comorbid and (4) discharge domains associated with preterm infant rehospitalization. STUDY DESIGN: Retrospective, cohort study of preterm infants discharged home from a level IV neonatal intensive care unit. Rates of unplanned and planned 6-month readmissions were assessed. The four domains were modeled incrementally and separately to predict relative and combined contributions to the readmission risk. RESULT: Out of 504 infants, 5% had 30-day readmissions (22 unplanned, three planned). By 6 months, 13% were rehospitalized (52 unplanned, 15 planned). Sixty-seven infants had 96 readmission events with 30% of readmission events elective. The four domains together predicted 78% of total 1-month, all 6 month and unplanned 6-month readmissions. Discharge complexity was as predictive as comorbidity in all models. CONCLUSION: These four-domain models were more predictive than single domains. Many total readmission events were planned, suggesting parsing planned and unplanned rehospitalizations may benefit quality improvement efforts. PMID- 26675000 TI - High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia. AB - OBJECTIVE: To identify the specific microRNA (miRNA) biomarkers of preeclampsia (PE), the miRNA profiles analysis were performed. STUDY DESIGN: The blood samples were obtained from five PE patients and five normal healthy pregnant women. The small RNA profiles were analyzed to identify miRNA expression levels and find out miRNAs that may associate with PE. The quantitative reverse transcriptase-PCR (qRT-PCR) assay was used to validate differentially expressed peripheral leucocyte miRNAs in a new cohort. RESULT: The data analysis showed that 10 peripheral leucocyte miRNAs were significantly differently expressed in severe PE patients. Four differently expressed miRNAs were successfully validated using qRT PCR method. CONCLUSION: We successfully constructed a model with high accuracy to predict PE. A combination of four peripheral leucocyte miRNAs has great potential to serve as diagnostic biomarkers of PE. PMID- 26675001 TI - Predictors of caregiver satisfaction with visiting nurse home visits after NICU discharge. AB - OBJECTIVE: High-risk infants are commonly referred to Visiting Nurse Association (VNA) agencies for post-hospitalization services after discharge from the neonatal intensive care unit (NICU). Little is known about the effectiveness and perceived benefits of routine VNA services for these infants. The objective of this study was to identify factors predictive of family satisfaction with VNA services after NICU discharge. STUDY DESIGN: This is an observational study using data collected from routine quality assurance phone calls to families after NICU discharge. The setting is a single NICU at a large, urban academic medical center in Boston, MA, USA. We included all hospitalized infants discharged from the NICU from 1 January 2008 to 31 July 2014. Predictors included markers of infant biological and social risk and a survey measure of parent and nurse perceptions of parents' preparedness at discharge. The outcome was parent response to the question, 'Did you find the VNA visit helpful?' at 2 weeks post discharge. RESULTS: Bivariate analyses showed perceived helpfulness of VNA visits associated with low maternal parity, lower 1-min Apgar score, lower birth weight and gestational age, diagnosis of respiratory distress syndrome and intraventricular hemorrhage and low discharge readiness scores. Only low maternal parity (odds ratio (OR) 1.82, 95% confidence interval (CI) 1.35, 2.46) and birth <35 weeks' gestation (OR 1.45, 95% CI 1.15, 1.83) were significant predictors in multivariable analysis. CONCLUSIONS: Low maternal parity and gestational age <35 weeks predicted parent satisfaction with VNA services. Referral for VNA services is common after NICU discharge. There are currently no guidelines indicating which infants and families stand to benefit most from such services. Our findings may help in developing and streamlining processes for post-hospitalization VNA service referrals for high-risk infants. PMID- 26675002 TI - Maternal juvenile rheumatoid arthritis may be associated with preterm birth but not poor fetal growth. AB - OBJECTIVE: Adverse pregnancy outcomes in mothers with juvenile rheumatoid arthritis (JRA) are not known. The objective of this study was to examine the risk of preterm birth and restricted fetal growth in pregnant mothers diagnosed with JRA, and to examine the impact of race/ethnicity and maternal age on this association. STUDY DESIGN: Hospital discharge records for mothers who gave birth in 2011 and 2012 were examined in the National Inpatient Sample (NIS) database. JRA, preterm birth (<37 weeks of gestation), birth weight that is small for gestational age (SGA) and other demographic and clinical variables were identified using ICD-9 (International Classification of Disease--9th revision) diagnostic codes. The associations of JRA with preterm birth and restricted fetal growth were examined controlling for confounding variables. RESULT: The sample included 8,273,987 birthing mothers, of these 1236 (0.01%) had JRA. The prevalence of preterm birth and SGA was 6.08% and 2.34%, respectively. Preterm birth in mothers with JRA was 12.9% compared with 6.1% in mothers without JRA with an adjusted odds ratio (OR) of 2.1 (confidence interval (CI): 1.74 to 2.42, P<0.001). The incidence of SGA in infants born to mothers with JRA was 3.34% compared with 2.34% in non-JRA mothers, which was not statistically significant. Adjusted OR for preterm birth in association with JRA among White mothers was 1.78 (CI: 1.41 to 2.24, P<0.001). However, Hispanic mothers with JRA (12%) were the ethnicity to suffer the most from preterm birth with an adjusted OR of 4.43 (CI: 2.97 to 6.62, P<0.001). Preterm birth among advanced maternal age (AMA) mothers with JRA was 25% compared with 7% in those without JRA with an adjusted OR of 5.42 (CI: 3.51 to 8.35, P<0.001). CONCLUSION: JRA is associated with preterm birth but not with SGA. This association is significantly influenced by race/ethnicity and maternal age. More studies are needed to examine these findings in relation to medications used, severity of the disease and exacerbation during pregnancy to understand the genetic/socioeconomic factors behind these racial/ethnic differences. PMID- 26675004 TI - Colorectal Cancer: Basic and Translational Research. AB - BACKGROUND: Colorectal cancer (CRC) still accounts for high mortality and morbidity of cancer patients worldwide. Early detection screening and therapeutic management of CRC are still traditional, with some important progress including cetuximab, microsatellite instability and the concept of CRC intrinsic subtypes. SUMMARY: Most achievements are derived from translational cancer research. Translational cancer research attempts to better understand the heterogeneity of human cancer and further turn discoveries into benefits for cancer patients. The four basic strategies of translational research can be depicted as (a) biomarker discovery, (b) identification in xenografts, (c) population-based verification and (d) clinical validation. PMID- 26675003 TI - Modeling Fatty Acid Transfer from Artery to Cardiomyocyte. AB - Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves. PMID- 26675005 TI - Sun safety knowledge and practice in UK postal delivery workers. AB - BACKGROUND: Postal delivery workers spend a large proportion of their work time outdoors, placing them at increased risk of skin cancer. To date, no studies have examined occupational sun safety knowledge and practice within this group in the UK. AIMS: To describe the occupational sun safety knowledge and practice of UK postal delivery workers and to investigate the association of demographic, personal and occupational factors with knowledge and practice in order to identify potential strategies for improving sun safety in this occupational group. METHODS: Postal delivery workers completed a questionnaire that collected data on occupational sun safety knowledge and practice in addition to demographic, personal and workplace characteristics. One-way analysis of variances were applied to assess differences in knowledge and practice by these characteristics. RESULTS: A total of 1153 postal delivery workers completed the questionnaire, a 60% response rate. Thirty-three per cent reported receiving sun safety training within the previous 12 months. The majority of respondents reported correct knowledge on three of the six domains and good practice on four of the six behavioural domains. However, only one-fifth of respondents reported wearing sunglasses and ensuring a plentiful intake of water. Knowledge and practice differed significantly according to demographic, personal and workplace characteristics. CONCLUSIONS: There is a need to raise the profile of occupational skin cancer in this occupational group and to increase the priority given to occupational sun safety policies alongside targeted and tailored interventions, the effect of which can be evaluated. PMID- 26675006 TI - Abuse and Neglect of Healthy Newborn by Parents: A Social Problem with a Long History. AB - A Two-day-old girl who was found in garbage by police and transferred to hospital. She was irritable and dehydrated; also there were burn injuries around her knees and right cheek. Her weight was 3100 grams and physical examinations were normal. Opium was found in urine. Phenobarbital (4 mg/kg/day intravenous every 12 hours) was started for her irritability. After 20 days, infant was entrusted to a welfare organization with coordination of social support of hospital. The prevention of child abuse and neglect is an urgent public health concern. Home visit by welfare organization has been proposed as a promising approach to prevent health and developmental problems among children. We report this case of an abused and neglected newborn. PMID- 26675007 TI - Plasmodium vivax Malaria in Pregnant Women in the Brazilian Amazon and the Risk Factors Associated with Prematurity and Low Birth Weight: A Descriptive Study. AB - INTRODUCTION: Plasmodium vivax is the most prevalent malaria species in the American region. Brazil accounts for the higher number of the malaria cases reported in pregnant women in the Americas. This study aims to describe the characteristics of pregnant women with malaria in an endemic area of the Brazilian Amazon and the risk factors associated with prematurity and low birth weight (LBW). METHODS/PRINCIPAL FINDINGS: Between December 2005 and March 2008, 503 pregnant women with malaria that attended a tertiary health centre were enrolled and followed up until delivery and reported a total of 1016 malaria episodes. More than half of study women (54%) were between 20-29 years old, and almost a third were adolescents. The prevalence of anaemia at enrolment was 59%. Most women (286/503) reported more than one malaria episode and most malaria episodes (84.5%, 846/1001) were due to P. vivax infection. Among women with only P. vivax malaria, the risk of preterm birth and low birth weight decreased in multigravidae (OR, 0.36 [95% CI, 0.16-0.82]; p = 0.015 and OR 0.24 [95% CI, 0.10 0.58]; p = 0.001, respectively). The risk of preterm birth decreased with higher maternal age (OR 0.43 [95% CI, 0.19-0.95]; p = 0.037) and among those women who reported higher antenatal care (ANC) attendance (OR, 0.32 [95% CI, 0.15-0.70]; p = 0.005). CONCLUSION: This study shows that P. vivax is the prevailing species among pregnant women with malaria in the region and shows that vivax clinical malaria may represent harmful consequences for the health of the mother and their offsprings particularly on specific groups such as adolescents, primigravidae and those women with lower ANC attendance. PMID- 26675009 TI - Growing Up in Poverty, Growing Old in Infirmity: The Long Arm of Childhood Conditions in Great Britain. AB - BACKGROUND: The ageing population poses a tremendous challenge in understanding the sources of inequalities in health. Though they appear to be far removed, childhood conditions are known to be inextricably linked with adult health, and in turn on health in later life. The long arm of childhood conditions hypothesis is often tested using recollection of childhood circumstances, but such subjective recall can yield potentially inaccurate or possibly biased inferences. We tested the long arm hypothesis on three outcomes in later life, arrayed from objective to subjective health, namely: gait speed, episodic memory and mental health. METHODS AND FINDINGS: We used the English Longitudinal Study of Ageing 2006 enriched with retrospective life history (N = 5,913). To deal with recall problems two solutions, covariate measurement and endogenous treatment models, were applied. Retrospective childhood material lack includes growing up without running hot or cold water, fixed bath, indoor lavatory and central heating. Adjustment is made for an extensive set of confounders including sex, age, adult health, wealth, education, occupation, social support, social connections, chronic conditions, smoking, drinking, and physical exercise. It is found that material poverty when growing up shows no association with health when growing old, assuming accurate recall. Once recall problems are controlled, we found that childhood material poverty changes inversely with later life health. CONCLUSION: A poorer childhood goes with slower gait, poorer memory and more depression in later life. This result provides a further impetus to eliminate child poverty. PMID- 26675010 TI - Optimal screening and donor management in a public stool bank. AB - BACKGROUND: Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. RESULTS: Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. CONCLUSIONS: More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly. PMID- 26675008 TI - In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors. AB - The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-beta3, BMP 2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors. PMID- 26675011 TI - Long-term (1998-2010) large-scale comparison of the ecological quality status of gulf of lions (NW Mediterranean) benthic habitats. AB - A comprehensive Mediterranean data set has been used to address 3 questions associated with the use of sensitivity/tolerance based biotic indices to infer the Ecological Quality status (EcoQs) of benthic habitats. Our results showed: (1) a significant effect of the reference database on derived sensitivity/tolerance measure (ES500.05) as well as associated Benthic Quality Index values and derived EcoQs; (2) a lack of correlation neither between BQI and AZTI Marine Biotic Index values nor between BQI and Multivariate-AZTI Marine Biotic Index values; (3) a lack of correlation between the values of the Benthic Habitat Quality Index (index derived from Sediment Profile Imagery) and those of either of the 3 tested biotic indices; and (4) a general agreement between the 3 tested biotic indices in describing the lack of global trend for the EcoQs of the Gulf of Lions despite the occurrence of significant changes in benthic macrofauna composition between 1998 and 2010. PMID- 26675012 TI - Pseudomonas helleri sp. nov. and Pseudomonas weihenstephanensis sp. nov., isolated from raw cow's milk. AB - Analysis of the microbiota of raw cow's milk and semi-finished milk products yielded seven isolates assigned to the genus Pseudomonas that formed two individual groups in a phylogenetic analysis based on partial rpoD and 16S rRNA gene sequences. The two groups could be differentiated from each other and also from their closest relatives as well as from the type species Pseudomonas aeruginosa by phenotypic and chemotaxonomic characterization and average nucleotide identity (ANIb) values calculated from draft genome assemblies. ANIb values within the groups were higher than 97.3 %, whereas similarity values to the closest relatives were 85 % or less. The major cellular lipids of strains WS4917T and WS4993T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol; the major quinone was Q-9 in both strains, with small amounts of Q-8 in strain WS4917T. The DNA G+C contents of strains WS4917T and WS4993T were 58.08 and 57.30 mol%, respectively. Based on these data, strains WS4917T, WS4995 ( = DSM 29141 = LMG 28434), WS4999, WS5001 and WS5002 should be considered as representatives of a novel species of the genus Pseudomonas, for which the name Pseudomonas helleri sp. nov. is proposed. The type strain of Pseudomonas helleri is strain WS4917T ( = DSM 29165T = LMG 28433T). Strains WS4993T and WS4994 ( = DSM 29140 = LMG 28438) should be recognized as representing a second novel species of the genus Pseudomonas, for which the name Pseudomonas weihenstephanensis sp. nov. is proposed. The type strain of Pseudomonas weihenstephanensis is strain WS4993T ( = DSM 29166T = LMG 28437T). PMID- 26675013 TI - Usefulness of 3D sonography of the central nervous system in neonates and infants in the assessment of intracranial bleeding and its consequences when examined through the anterior fontanelle. AB - Due to the possibility to examine at the patient bedside or incubator, ultrasound imaging of the central nervous system, particularly through the anterior fontanelle, is the most common diagnostic examination performed in neonates and infants with neurological problems. Despite its common application, this method has certain limitations. These limitations are associated with cross-sections of the cerebral structures that can be obtained when examining through the anterior fontanelle. The aim of the paper was to assess the usefulness of three dimensional sonography of the central nervous system in neonates and infants in the assessment of intracranial bleeding and its consequences when examined through the anterior fontanelle. The study enrolled 283 patients treated at the Pediatric Teaching Hospital at the Medical University of Lublin in whom a transfontanelle cerebral examination was indicated. The two- and three dimensional ultrasound examinations of the central nervous system were conducted in 283 patients aged from 1 day to 18 months (mean age: 2 months). 254 three dimensional examinations were of diagnostic value. The number of detected pathological lesions was higher in a statistically significant way (p = 0.007) in the three-dimensional ultrasound examination. In the authors' own studies, the highest sensitivity and statistically significant superiority of the three dimensional method over the two-dimensional one referred to detecting intraventricular or intracerebral hemorrhages. Novel techniques of ultrasound imaging, including the three-dimensional one, have undoubtedly increased the diagnostic possibilities of sonography and, at the same time, retained all its advantages. PMID- 26675014 TI - Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers: Flowcytometry Measurements of T, B, NK and NKT Cells. AB - The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant "Kozloduy", Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with regard to cumulative doses, length of service and age. The average values of the studied parameters of cellular immunity were in the reference range relative to age and for most of the workers were not significantly different from the control values. Low doses of ionizing radiation showed some trends of change in the number of CD3+CD4+ helper-inducer lymphocytes, CD3+ CD8+ and NKT cell counts. The observed changes in some of the studied parameters could be interpreted in terms of adaptation processes at low doses. At doses above 100-200 mSv, compensatory mechanisms might be involved to balance deviations in lymphocyte subsets. The observed variations in some cases could not be attributed only to the radiation exposure because of the impact of a number of other exogenous and endogenous factors on the immune system. PMID- 26675015 TI - Potential Role of Phosphorylation as a Regulator of Aspartyl-(asparaginyl)-beta hydroxylase: Relevance to Infiltrative Spread of Human Hepatocellular Carcinoma. AB - Abundant expression of aspartyl-(asparaginyl)-beta-hydroxylase (AAH) correlates with infiltrative growth of hepatocellular carcinoma (HCC). Herein, we examine the role of phosphorylation in relation to AAH's protein expression, hydroxylase activity, promotion of cell motility, and activation of Notch signaling in human Huh7 hepatoma cells. Predicted glycogen synthase kinase-3beta (GSK-3beta), protein kinase A (PKA), protein kinase C (PKC), and casein kinase 2 (CK2) phosphorylation sites encoded by human AAH cDNA were ablated by S/T->A site directed mutagenesis using N-Myc-tagged constructs in which gene expression was controlled by a cytomegalovirus promoter. Functional consequences were assessed in transiently transfected Huh7 cells. Cells transfected with wildtype AAH had significantly increased AAH expression, catalytic activity, HES-1 expression, and directional motility relative to controls. Single phosphorylation site mutations in the C-terminus largely abrogated these effects and further inhibited catalytic activity relative to that in cells transfected with empty vector, whereas the effects of single point mutations within the N-terminus were more varied. In contrast, AAH cDNAs carrying multiple phosphorylation site mutations exhibited wildtype levels of AAH catalytic activity suggesting that the effects of AAH phosphorylation are complex and non-uniform. AAH expression and function can be modulated by direct phosphorylation of the protein. These findings suggest additional strategies for inhibiting infiltrative growth of HCC. PMID- 26675016 TI - A Genome-Wide Association Study Uncovers a Genetic Locus Associated with Thoracic to-Hip Ratio in Koreans. AB - The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 * 10-6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 * 10-2; rs2074356: p = 1.10 * 10-2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = -0.008624, p = 6.19 * 10-9; rs2074356: effect size = -0.008762, p = 1.89 * 10-8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients' risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men. PMID- 26675017 TI - [The middle east respiratory syndrome-we are concerned but no panic]. PMID- 26675018 TI - [Preliminary suggestions on revision of de-escalating strategy of antibacterial therapy in severe infections]. PMID- 26675019 TI - [Viewpoints of undefined invasive fungal disease]. PMID- 26675020 TI - [Do not resuscitate and hospice care]. PMID- 26675021 TI - [Antimicrobial resistance monitoring of gram-negative bacilli isolated from 15 teaching hospitals in 2014 in China]. AB - OBJECTIVE: To investigate the current situation of antimicrobial resistance of nosocomial gram-negative bacilli in 2014 in China. METHODS: About 1 430 consecutive and non-repetitive strains of gram-negative bacilli were isolated from 15 teaching hospitals from March to August in 2014. All of these isolates were sent to the central laboratory for reidentification and susceptibility testing. The minimal inhibitory concentration (MIC) of meropenem and other antibacterial agents were determined by agar dilution method. The data were analyzed by using WHONET-5.6 software. RESULTS: The activity of antimicrobial agents against Enterobacteriaceae was listed as followings in descending order of susceptibility: meropenem (94.7%, 913/964), amikacin (94.4%, 910/964), imipenem (88.5%, 853/964), ertapenem (87.8%, 847/964), piperacillin-tazobactam (87.2%, 841/964), cefoperazone-sulbactam (86.7%, 836/964), polymyxin B (77%, 742/964), cefepime (74.5%, 718/964), cefiazidime (71.8%, 692/964), levofloxacin (71.1%, 685/964), ciprofloxacin (67.7%, 653/964), minocyline (64.2%, 619/964), ceftriaxone (56.8%, 548/964), cefotaxime (55.8%, 538/964), cefoxitin (45.5%, 439/964). The prevalence of extended-spectrum beta-lactamases (ESBLs) was 57.6% (114/198) in E. coli and 24.6% (49/199) in Klebsiella pneumonia. The sensitivity of E. coli to carbapenems, amikacin, piperacillin-tazobactam, polymyxin B and cefoperazone-sulbactam was all over 80%. However, over 60% E. coli strains were resistant to ciprofloxacin, levofloxacin, ceftriaxone and cefotaxime. Polymyxin B was the most susceptible antibiotic to Klebsiella pneumoniae (99.5% sensitive), followed by amikacin (89.9%), meropenem (86.4%), imipenem (86.4%) and piperacillin-tazobactam (81.9%), while ceftriaxone (60.8%) and cefotaxime (59.8%) were less sensitive. The activity of antimicrobial agents against E. cloacae, E. aerogenes and Citrobacter freundii was listed as followings in descending order of susceptibility: meropenem (96.1%-97.4%), imipenem (95.1%-97.1%), polymyxin B (92.6%-99.0%), cefoperazone/sulbactam (87.3%-92.6%), ertapenem (85.6%-93.3%), piperacillin-tazobactam (65.0%-89.8%). The susceptibility rates of meropenem, cefoperazone-sulbactam, piperacillin-tazobactam, cefepime to Proteus mirabilis, Proteus vulgaris and Morganella morganii were all more than 90.0%. The most active agents against Pseudomonas aeruginosa were polymyxin B (99.5%), followed by amikacin (92.0%) and ciprofloxacin (82.1%). A. baumanni was most susceptible to polymyxin B (99.0%), while resistant to imipenem, meropenem and cefoperazone sulbactam (29.2%, 28.2% and 29.7% respectively), mediate to minocycline (67.0%). Based on the new breakpoints for cefepime to Enterobacteriaceae, the drug susceptible rates decreased 25.8% to E. coli and 14.7% to E. cloacae. CONCLUSIONS: Carbapenems remain high susceptibility against Enterobacteriaceae, however carbapenem-resistant Enterobacteriaceae (CREs) have emerged. The sensitivity of Enterobacteriaceae against cefepime has been decreased according to the new breakpoint. Multi-drug resistant A. baumanni should be monitored persistently. PMID- 26675022 TI - [The clinical characteristics of twenty-five cases of acute HIV-1 infection in China]. AB - OBJECTIVE: To summarize the clinical features, immunological and virological characteristics of HIV-1 infected patients in the acute phase for the sake of improving the understanding of acute HIV-1 infection and early diagnosis. METHODS: To retrospectively analyze the clinical manifestation and laboratory data of 25 patients with acute HIV infection, who were admitted to the Department of Infectious Diseases, Peking Union Medical College Hospital from 2006 to 2013. RESULTS: Among the total 25 patients, 19 (76%) patients were sexually transmitted, including 17 (68%) of whom were homosexual. Twenty two (88%) patients presented significant symptoms. Common symptoms consisted of fever (15 patients, 60%), cervical lymphoadenopathy (8 patients, 32%), skin rashes (6 patients, 24%), diarrhea (5 patients, 20%), shortness of breath (3 patients, 12%), sore throat (3 patients, 12%), and cough (3 patients, 12%), while only one case represented as Guillain-Barr syndrome, upper arm cellulitis, headache and vomiting, and perianal abscess. Laboratory examination indicated elevated peripheral lymphocytes (13 patients, 52%), abnormal liver function (11 patients, 44%), thrombocytopenia (1 patients, 4%). Notably, 2 patients (8%) revealed negative results of HIV antibody, who were diagnosed with positive plasma viral load. The average viral load was (4.68 +/- 0.83) lg copies/ml. CD(+)(4) T cell count was 473 (343,621) cells/ul. CD(+)(8) T cell count was 1 296 (997, 2 177) cells/ul with maximal value of 7 984 cells/ul. The CD4/CD8 ratio was 0.33 (0.22, 0.53) including 24 (96%) patients with obvious inverted ratio. The positive rates of immune activation markers HLA-DR and CD38 on the surface of CD(+)(8) T cells were (74.9 +/- 16.1) % and (84.9 +/- 12.5) % respectively. The viral load had a significant positive correlation with the expression of HLA-DR and CD38. CONCLUSIONS: The most common symptoms of acute HIV-1 infection are fever, cervical lymphadenopathy, skin rashes and diarrhea. Significantly elevated CD(+)(8) T cell count, inverted CD4/CD8 ratio and abnormal immune activation markers contribute to the early diagnosis of acute HIV infection. PMID- 26675023 TI - [Long-term outcome of patients discharged with fever of unknown origin in the Department of General Internal Medicine of Peking Union Medical College Hospital]. AB - OBJECTIVE: To investigate the clinical characteristics and outcome of patients with undiagnosed fever of unknown origin (FUO). METHODS: To retrospectively review the clinic data of patients discharged with FUO from the Department of General Internal Medicine, Peking Union Medical College Hospital during 2004 to 2008. Medical records and phone call follow-up data were collected until 2014. RESULTS: Among 758 in-patients diagnosed with FUO, 70 patients still discharged with FUO were enrolled in this study, including 23 males and 47 females. There were 14 missing patients. Finally, definite diagnoses were made in 20 patients by clinical reassessments, empirical therapy or repeated biopsies, in whom 3 patients dying from underlying diseases. A total of 36 patients did not get final diagnoses, while fever was relieved in 23 patients, including 10 treated with corticosteroids or non-steroid anti-inflammatory drugs (NSAIDs) from 1 month to 12 months due to suspected connective tissue diseases. Another 3 patients still had episodic fever. Seven patients died shortly after discharge. There were 3 dying in the long-term follow-up. The overall FUO-related mortality was 18.6%. Mortality was correlated with the number of dysfunctional organs, especially cytopenia, coagulation dysfunction, bleeding events, respiratory damage and acute renal failure with OR 2.1, 9.9, 3.3 and 6.6 (P < 0.05) respectively. CONCLUSIONS: Close follow-up, intermittent clinical reassessments, repeated biopsies will contribute to the diagnosis of patients discharged with FUO. Empirical therapy with corticosteroids, NSAIDs or anti-tubercular drugs in selected patients may be safe and effective. Mortality rates increased with impaired organs, especially the hematological, respiratory and renal systems. PMID- 26675024 TI - [The application of combined central venous pressure and oxygen metabolism parameters monitoring in diagnosing septic shock-induced left ventricular dysfunction]. AB - OBJECTIVE: To evaluate the value of central venous pressure (CVP), central venous oxygen saturation (ScvO2) and venous-arterial carbon dioxide partial pressure gradient (Pv-aCO2)) in the diagnosis of septic shock-induced left ventricular dysfunction. METHODS: Consecutive patients with septic shock were enrolled from September 2013 to September 2014 in ICU at Peking Union Medical College Hospital. The data of CVP, Pv-aCO2) and ScvO2) were recorded and analyzed. According to the left ventricular ejection fraction (LVEF) tested by bedside echocardiography, the patients were divided into two groups: new onset of left ventricular dysfunction (LVEF < 50%) group and non-left ventricular dysfunction (LVEF >= 50%) group. A diagnostic model was created by logistic regression. The diagnostic performance and cut-off values of CVP, Pv-aCO2, ScvO2) were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Among 93 patients enrolled, 39 were diagnosed with left ventricular dysfunction. In the new onset group, CVP [(12.5 +/- 3.9) mmHg (1 mmHg = 0.133 kPa) vs (10.4 +/- 2.5) mmHg; P = 0.005] and Pv-aCO2[(7.5 +/- 3.9) mmHg vs (4.5 +/- 2.6) mmHg; P < 0.001] were significantly higher than those in the non-left ventricular dysfunction group, while Scv2 [(62.4 +/- 10.5)% vs (72.6 +/- 9.0)%; P < 0.001] was significantly lower. As far as the diagnostic value of these three parameters were concerned for left ventricular dysfunction, the sensitivity of CVP >= 12.5 mmHg was 46.2%, specificity 81.5% with an area under ROC curve (AUCROC) 0.674; the sensitivity of Pv-aCO2>= 5.0 mmHg 76.9%, specificity 37.0%, AUCROC 0.738; the sensitivity of ScvO2<= 65.8% 64.1%, specificity 78.6%, AUCROC 0.775. When the cut-off values were determined by ROC, the diagnostic performance of the model was >= 0.377 with the sensitivity, specificity and AUCROC 82.1%, 79.6% and 0.835, respectively. CONCLUSION: In patients with septic shock, the logistic regression model established by CVP, Pv-aCO2and ScvO2contributes to the diagnosis of septic shock induced left ventricular dysfunction. PMID- 26675025 TI - [Association between Tbx20 gene polymorphism and congenital atrial septal defects]. AB - OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SPN) of Tbx20 gene and congenital atrial septal defects (ASD) in the Xinjiang Han population. METHODS: A total of 214 ASD patients and 382 controls were included in the present study. Two SNPs (rs17675131, rs4720169) in Tbx20 gene were genotyped by TaqMan SNP genotyping method. RESULTS: The distribution of the rs17675131 of Tbx20 were significantly different between normal controls and ASD patients (P = 0.014), in which both the A/G allele distribution (P = 0.004) and the dominant model (GG vs AG + AA) were significantly different between the 2 groups (P = 0.007, OR = 0.626). Same is true for the rs4720169 SNP. Its genotype showed significantly different distributions between the 2 groups (P = 0.016) specifically for the A/G allele distribution frequencies (P = 0.016) and the recessive model (AA vs AG + GG) (P = 0.008, OR = 1.96). The A-A haplotype was found to be associated with ASD. CONCLUSION: Both rs17675131 and rs4720169 of Tbx20 gene are associated with congenital ASD in the Xinjiang Han population in China. PMID- 26675026 TI - [Esophageal motility abnormalities and their impact on esophageal acid exposure in patients with gastroesophageal reflux disease]. AB - OBJECTIVE: To identify the characteristics of esophageal motility abnormalities in patients with gastroesophageal reflux disease (GERD) and its influence on esophageal acid exposure. METHODS: Patients with typical reflux symptoms and diagnosis of reflux esophagitis (RE) or non-erosive reflux disease (NERD), and healthy subject were enrolled in this prospective controlled study. The esophageal manometry and esophageal 26 hours pH monitoring were performed. GERD patients were divided into 3 groups according to their esophageal motility abnormalities: 1 low lower esophageal sphincter pressure (LESP) group, 2 ineffective esophageal motivation (IEM) group, 3 IEM and low LESP group. Esophageal acid exposure was analyzed among different groups. RESULTS: A total of 27 GERD patients (15 RE, 12 NERD) and 10 healthy subjects were enrolled in this study. The esophageal motility abnormalities in GERD patients mainly presented as the decrease of LESP and distal esophageal body pressure. The proportion of 3 kinds of esophageal motility abnormalities has significant difference between RE and NERD patients (P = 0.017). In IEM and low LESP group, all patients suffered from RE, with the total number of acid exposure, the total acid exposure time and the acid exposure time in fasting higher than those in low LESP group [98.0 (63.3, 282.8) times vs 41.0 (25.0, 82.0) times, P = 0.029; 11.7% (4.1%, 30.0%) vs 2.2% (1.4%, 9.6%), P = 0.045; 2.6% (0.9%, 4.9%) vs 0.0 (0.0, 1.2%), P = 0.015]. CONCLUSIONS: Esophageal motility abnormalities in GERD patients are characterized as low LESP and IEM in distal esophagus. The coexistence of low LESP and IEM exacerbates esophageal acid exposure, which might explain the mechanism of esophageal mucosal injury in RE patients. PMID- 26675027 TI - Multilevel fluidic flow control in a rotationally-driven polyester film microdevice created using laser print, cut and laminate. AB - This paper presents a simple and cost-effective polyester toner microchip fabricated with laser print and cut lithography (PCL) to use with a battery powered centrifugal platform for fluid handling. The combination of the PCL microfluidic disc and centrifugal platform: (1) allows parallel aliquoting of two different reagents of four different volumes ranging from nL to MUL with an accuracy comparable to a piston-driven air pipette; (2) incorporates a reciprocating mixing unit driven by a surface-tension pump for further dilution of reagents, and (3) is amenable to larger scale integration of assay multiplexing (including all valves and mixers) without substantially increasing fabrication cost and time. For a proof of principle, a 10 min colorimetric assay for the quantitation of the protein level in the human blood plasma samples is demonstrated on chip with a limit of detection of ~5 mg mL(-1) and coefficient of variance of ~7%. PMID- 26675028 TI - Small Bowel Carcinoids: A Single Surgeon's Experience in Southern India. AB - INTRODUCTION: Small bowel carcinoid tumours are indolent neuroendocrine tumours usually seen in the 6(th) and 7(th) decades. Most often, they are silent with non specific symptoms. They generate serotonin, provoking a desmoplastic reaction in the mesentery leading to bowel ischemia and obstruction. While CECT abdomen can help raise suspicion and show regional spread, elevated 24-hour urinary 5-HIAA levels, histopathology and immunohistochemistry for Chromogranin A are confirmatory. AIM: To analyse a single surgeon's experience of clinical features and diagnosis of carcinoid tumours of the small intestine. SETTING AND DESIGN: Retrospective study conducted at MS Ramaiah Medical College and Hospital, Bangalore, India. MATERIALS AND METHODS: Fourteen cases of carcinoid of the small bowel presenting to our institution over a 9-year period between December 2005 and November 2014 comprised the study. This included 10 males to 4 females aged 43 to 67 years (Mean: 54.4 years). The patients were investigated using x-ray abdomen, barium study, CECT abdomen, colonoscopy and 24-hour urinary 5- HIAA levels. All patients were surgically treated and histological examination of the resected tumours and immunohistochemistry for Chromogranin A was performed. RESULTS: Twelve patients with ileal carcinoids presented with long standing intestinal colic and sub-acute obstruction. Two patients with jejunal carcinoids had epigastric pain. X-ray abdomen was suggestive of small bowel obstruction in 12 patients. CECT abdomen done in 6 patients, showed ileal narrowing causing proximal dilatation; and cocooining of ileal loops at ileo-caecal junction in 2 cases. Ten patients underwent segmental resection-anastomosis of the tumour bearing intestine while 4 patients underwent a right hemicolectomy. Lymph node spread was seen in 8 patients of whom 4 had liver metastases. Histopathology and Chromogranin A positivity confirmed the diagnoses. Postoperatively, 24-hour urinary 5-HIAA was mildly elevated in 2 patients. 12 patients were disease free at mean follow up of 4.3 years. 2 patients died due to inanition at 3 and 5 months postoperatively. CONCLUSION: Carcinoid tumours of small intestine are uncommon in southern India. But they should be considered as differential diagnosis when intestinal tuberculosis is suspected in the elderly presenting with intestinal colic or sub-acute obstruction. They are associated with good prognosis after adequate resection. PMID- 26675030 TI - Bladder Leiomyosarcoma 25 Years after Treatment with Cyclophosphamide in Patient with History of Retinoblastoma. AB - The objective of this case report is to present a rare bladder tumour in a young patient 25 years after the treatment with cyclophosphamide because of a neuroblastoma of the right eye. The first symptom of the tumour was macroscopic haematuria with dysuria and pollakiuria. The final diagnosis was dictaminated by the pathologist and the best treatment option was radical cystoprostatectomy. Leiomyosarcoma was presented in a 26-year-old patient like the third different tumour, the second was an esphenoidal meningioma. At the 8th year of follow-up after the radical surgery, the patient is free of bladder disease. Bladder leiomyosarcoma is a rare tumour of the bladder and its early diagnosis and treatment are mandatory for best prognosis. PMID- 26675029 TI - Tissue reactions of abdominal integuments to surgical sutures in sonography. AB - Classical abdominal surgeries usually require long incisions of the abdominal integuments followed by tight closure with adequate suturing material. Nonabsorbable sutures may cause various reactions, including granuloma reactions, both sterile and inflammatory. THE AIM OF THE STUDY: The aim of the study was to analyze prospective ultrasound examinations of the abdominal integuments in order to detect tissue reactions to surgical sutures. MATERIAL AND METHODS: For 10 years, ultrasound examinations of the abdominal integuments involved the assessment of surgical scars in all patients who underwent open or closed surgeries for various reasons (in total 2254 patients). Ultrasound examinations were performed only with the use of linear probes with the frequency ranging from 7 to 12 MHz. Each scar in the abdominal integuments was scanned in at least two planes. When a lesion was detected, the image was enlarged and the transducer was rotated by approximately 180 degrees in order to capture the dimensions of the granuloma and the most characteristic image of the suture. Moreover, vascularization of the lesion was also assessed with the use of color Doppler mode set to detect the lowest flows. RESULTS: All granulomas (19 lesions, two in one patient) created hypoechoic oval or round nodules, were relatively well circumscribed and their size ranged from 8 * 4 mm to 40 * 14 mm. In the center of the lesion, it was possible to notice a thread that was coiled to various degrees and presented itself as a double, curved hyperechoic line. In 9 out of 19 granulomas, slight peripheral vascularization was observed. The substantial majority of the lesions (n = 15) were in contact with the fascia. In seven patients, compression with the transducer induced known local pain (n = 4) or intensified pain that had already been present (n = 3); all of these granulomas infiltrated the fascia and showed slight peripheral vascularization. Cutaneous fistulae developed in two patients with purulent reactions to the running stitch (in one patient - two fistulae). CONCLUSIONS: Suture granulomas in the abdominal integuments manifest themselves as nodular hypoechoic lesions, usually localized at the edge of the fascia - subcutaneous fat. A pathognomonic sign of this type of granulomas is the presence of a thread in their center that usually manifests itself as a chaotically shaped, double hyperechoic line. In some granulomas, particularly those with clinical presentation, slight peripheral vascularization is observed. PMID- 26675031 TI - How should individual participant data (IPD) from publicly funded clinical trials be shared? AB - BACKGROUND: Individual participant data (IPD) from completed clinical trials should be responsibly shared to support efficient clinical research, generate new knowledge and bring benefit to patients. The Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) has developed guidance to facilitate the sharing of IPD from publicly funded clinical trials. METHODS: Development of the guidance was completed over four phases which included a focussed review of policy documents, a web-based survey of the UK Clinical Research Collaboration (CRC) Registered Clinical Trials Units (CTU) Network, participation of an expert committee and an open consultation with the UKCRC Registered CTU Network. The project was funded by the MRC HTMR (MR/L004933/1-R39). RESULTS: Good practice principles include: (i) the use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (ii) seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (iii) establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UKCRC Registered CTU Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance. CONCLUSIONS: Implementation of these principles will improve transparency, increase the coherent sharing of IPD from publicly funded trials, and help publicly funded trials to adhere to trial funder and journal requirements for data sharing. PMID- 26675032 TI - Only-Child Status in Relation to Perceived Stress and Studying-Related Life Satisfaction among University Students in China: A Comparison with International Students. AB - OBJECTIVES: University students in general face multiple challenges, which may affect their levels of perceived stress and life satisfaction. Chinese students currently face specific strains due to the One-Child Policy (OCP). The aim of this study was to assess (1) whether the levels of perceived stress and studying related life satisfaction are associated with only-child (OC) status after controlling for demographic and socio-economic characteristics and (2) whether these associations differ between Chinese and international students. MATERIALS AND METHODS: A cross-sectional health survey based on a self-administrated standardised questionnaire was conducted among 1,843 (1,543 Chinese, 300 international) students at two Chinese universities in 2010-2011. Cohen's Perceived Stress Scale (PSS-14) and Stock and Kraemer's Studying-related Life Satisfaction Scale were used to measure perceived stress and studying-related life satisfaction respectively. Multivariable logistic regression analyses were used to examine the associations of OC status with perceived stress and studying related life satisfaction by sex for Chinese students and international students separately. RESULTS: The Chinese non-only-children (NOCs) were more likely to come from small cities. Multivariable regression models indicate that the Chinese NOCs were more stressed than OCs (OR = 1.39, 1.11-1.74) with a stronger association in men (OR = 1.48, 1.08-2.02) than women (OR = 1.26, 0.89-1.77). NOCs were also more dissatisfied than their OC fellows in the Chinese subsample (OR = 1.37, 1.09-1.73). Among international students, no associations between OC status and perceived stress or studying-related life satisfaction were found. CONCLUSIONS: To promote equality between OCs and NOCs at Chinese universities, the causes of more stress and less studying-related life satisfaction among NOCs compared to OCs need further exploration. PMID- 26675033 TI - Dietary calcium intake and the risk of colorectal cancer: a case control study. AB - BACKGROUND: High intake of dietary calcium has been thought to be a protective factor against colorectal cancer. To explore the dose-response relationship in the associations between dietary calcium intake and colorectal cancer risk by cancer location, we conducted a case-control study among Korean population, whose dietary calcium intake levels are relatively low. METHODS: The colorectal cancer cases and controls were recruited from the National Cancer Center in Korea between August 2010 and August 2013. Information on dietary calcium intake was assessed using a semi-quantitative food frequency questionnaire and locations of the colorectal cancers were classified as proximal colon cancer, distal colon cancer, and rectal cancer. Binary and polytomous logistic regression models were used to evaluate the association between dietary calcium intake and risk of colorectal cancer. RESULTS: A total of 922 colorectal cancer cases and 2766 controls were included in the final analysis. Compared with the lowest calcium intake quartile, the highest quartile group showed a significantly reduced risk of colorectal cancer in both men and women. (Odds ratio (OR): 0.16, 95% confidence interval (CI): 0.11-0.24 for men; OR: 0.16, 95% CI: 0.09-0.29 for women). Among the highest calcium intake groups, decrease in cancer risk was observed across all sub-sites of colorectum in both men and women. CONCLUSION: In conclusion, calcium consumption was inversely related to colorectal cancer risk in Korean population where national average calcium intake level is relatively lower than Western countries. A decreased risk of colorectal cancer by calcium intake was observed in all sub-sites in men and women. PMID- 26675034 TI - Living Long and Well: Prospects for a Personalized Approach to the Medicine of Ageing. AB - Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large scale cohort studies in humans, similar systematic studies in model organisms as well as detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and they can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains or genetic reference populations of mice. Combining the two, a comprehensive picture of the various determinants of ageing and 'health span' can be studied in detail, and an appreciation of the relevance of results from model organisms to humans is emerging. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase the success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of the health span enables us to refocus health care spending on individual prevention, starting in late adulthood, and on the brief period of morbidity at very old age. PMID- 26675035 TI - Resting Orientations of Dinosaur Scapulae and Forelimbs: A Numerical Analysis, with Implications for Reconstructions and Museum Mounts. AB - The inclination of the scapular blade and the resting pose of the forelimb in dinosaurs differ among reconstructions and among skeletal mounts. For most dinosaurian taxa, no attempt has previously been made to quantify the correct resting positions of these elements. Here, we used data from skeletons preserved in articulation to quantify the resting orientations of the scapula and forelimb in dinosaurs. Specimens were included in the study only if they were preserved lying on their sides; for each specimen the angle between forelimb bones at a given joint was included in the analysis only if the joint was preserved in articulation. Using correlation analyses of the angles between the long axis of the sacrum, the first dorsal centrum, and the scapular blade in theropods and Eoraptor, we found that vertebral hyperextension does not influence scapular orientation in saurischians. Among examined taxa, the long axis of the scapular blade was found to be most horizontal in bipedal saurischians, most vertical in basal ornithopods, and intermediate in hadrosauroids. We found that in bipedal dinosaurs other than theropods with semilunate carpals, the resting orientation of the elbow is close to a right angle and the resting orientation of the wrist is such that the hand exhibits only slight ulnar deviation from the antebrachium. In theropods with semilunate carpals the elbow and wrist are more flexed at rest, with the elbow at a strongly acute angle and with the wrist approximately at a right angle. The results of our study have important implications for correct orientations of bones in reconstructions and skeletal mounts. Here, we provide recommendations on bone orientations based on our results. PMID- 26675036 TI - Epithelial-Myoepithelial Carcinoma of the Salivary Gland Harboring HRAS Codon 61 Mutations With Lung Metastasis. AB - Here, we report a case involving a 43-year-old man diagnosed with Burkitt lymphoma in 2007. At the same time, 2 small lung nodules were incidentally found; however, they presented no indication of growth throughout the follow-up period. However, a 1.5-cm nodule located in the right parotid gland in 2010 gradually increased in size to 2.8 cm by 2012. A parotidectomy revealed an epithelial myoepithelial carcinoma, characterized by biphasic tubular structures and solid areas presenting myoepithelial overgrowth. Tumor necrosis and regional lymph node invasion were also observed. During clinical follow-up in 2013, a new 1.3-cm nodule was identified in the left lower lobe of the lung, which enlarged to 3 cm by 2014. Wedge resection of the left lung nodules revealed round nodes with well defined borders. Histologically, these lung tumors predominantly comprised spindle-shaped myoepithelial cells with occasional tubular structures. Numerous cleft-like spaces lined by entrapped TTF-1-immunoreactive pneumocytes were observed inside the nodules. The lung nodules were characterized by a morphology similar to that of the parotid cancer. Epithelial-myoepithelial carcinoma with lung metastasis was confirmed by molecular testing, which revealed identical HRAS codon 61 (Q61K) mutations in the primary parotid tumor as well as in the lung metastases. PMID- 26675037 TI - Coordination Modes of Americium in the Am2(C2O4)3(H2O)6.4H2O Oxalate: Synthesis, Crystal Structure, Spectroscopic Characterizations and Comparison in the M2(C2O4)3(H2O)6.nH2O (M = Ln, An) Series. AB - Americium oxalate single crystals, Am2(C2O4)3(H2O)6.4H2O, were prepared by in situ oxalic acid generation by slow hydrolysis of the diester. Their structure was determined by single-crystal X-ray diffraction and was solved by the direct methods and Fourier difference techniques. The structure (space group P21/c, a = 11.184(4) A, b = 9.489(4) A, c = 10.234(4) A, beta = 114.308(8) degrees , Z = 2) consists of layers formed by six-membered rings of actinide metals connected through oxalate ions. The americium atoms are nine-coordinated by six oxygen atoms from three bidentate oxalate ligands and three water molecules. The distances within the coordination sphere as well as infrared and Raman spectra of several isostructural lanthanide (Ce(III), Pr(III), Nd(III), Sm(III), Gd(III)) and actinide (Pu(III), Am(III)) oxalates were compared to evaluate the similarities and the differences between the two series. PMID- 26675039 TI - Serum BPIFB4 levels classify health status in long-living individuals. AB - BACKGROUND: People that reach extreme ages (Long-Living Individuals, LLIs) are object of intense investigation for increase/decrease of genetic variant frequencies, genetic methylation levels, protein abundance in serum and tissues. The aim of these studies is the discovery of the mechanisms behind LLIs extreme longevity and the identification of markers of well-being. We have recently associated a BPIFB4 haplotype (LAV) with exceptional longevity under a homozygous genetic model, and identified that CD34(+) of LLIs subjects express higher BPIFB4 transcript as compared to CD34(+) of control population. It would be of interest to correlate serum BPIFB4 protein levels with exceptional longevity and health status of LLIs. METHODS: Western blots on cellular medium to detect BPIFB4 secretion in transfected HEK293T cells with plasmid carrying BPIFB4 and ELISA on LLIs serum to detect BPIFB4 levels. RESULTS: Here we show that BPIFB4 is a secreted protein and its levels are increased in serum of LLIs, and high BPIFB4 levels classify their health status. CONCLUSIONS: Serum BPIFB4 protein levels classify longevity and health status in LLIs. Further studies are required to evaluate the possible role of BPIFB4 in monitoring disease progression. PMID- 26675038 TI - Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. AB - In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015. PMID- 26675040 TI - Abdominal integument atrophy after operative procedures. AB - THE AIM OF THE STUDY: was to analyze clinical material concerning postoperative atrophy of abdominal integument. MATERIAL AND METHODS: The evaluated group consisted of 29 patients with sonographically revealed atrophy of the abdominal wall. Those changes were observed after various surgical procedures: mainly after long, anterolateral laparotomies or several classical operations. Ultrasound examinations up to the year 2000 were performed with analog apparatus, in the latter years only with digital apparatus with linear transducers (7-12 MHz) and sometimes convex type conducers (3-5 MHz). The location, size and intestine stratified wall structure were evaluated. In each case the integument thickness was measured in millimeters in the site of the greatest atrophy and it was compared with the integument thickness from the side that had not been operated which enabled the calculation of the percentage reduction of integument in the area of the scar. RESULTS: In 3 patients who underwent several laparotomies there was a total reduction of muscular mass in the operated area. In these cases we stated only skin and slightly echogenic subcutaneous strand; probably corresponding to fibrous tissue - the thickness of integument in this area was in the range from 3 to 8 mm. In the remaining 26 patients the integument atrophy on the scar level included muscles in a greater extent and covered an extensive area after classical urological procedures on the upper urinary tract: after nephrectomy and even ureter stone evacuation or kidney cyst excision by means of classical anterolateral approach with the integument incision on the length of almost 20 cm. Reduction in the integument thickness was observed on the smaller area after classical cholecystectomies, appendectomies and other surgical procedures with the incision across the integument. The integument atrophy in the operated sites expressed in absolute numbers was in the range of 7-20 mm (average 14 mm). These values are markedly lower than the comparative integument thickness on the not operated side: 17-52 mm (average 25.4 mm). The percentage value of the integument thickness reduction oscillated in the range of 32-67% (average 44.2%). In most cases the atrophy involved all layers of the abdominal wall, what demonstrated as regional prominence of the integument, mimicking the presence of hernia. CONCLUSIONS: Ultrasonography allows precise evaluation of the size and extent of atrophy as well as depiction of other lesions simulating that effect. Establishing the correct diagnosis should prevent the unnecessary reconstructions of the abdominal integument. PMID- 26675041 TI - Leucanicidin and Endophenasides Result from Methyl-Rhamnosylation by the Same Tailoring Enzymes in Kitasatospora sp. MBT66. AB - The increasing bacterial multidrug resistance necessitates novel drug-discovery efforts. One way to obtain novel chemistry is glycosylation, which is prevalent in nature, with high diversity in both the sugar moieties and the targeted aglycones. Kitasatospora sp. MBT66 produces endophenaside antibiotics, which is a family of (methyl-)rhamnosylated phenazines. Here we show that this strain also produces the plecomacrolide leucanicidin (1), which is derived from bafilomycin A1 by glycosylation with the same methyl-rhamnosyl moiety as present in the endophenasides. Immediately adjacent to the baf genes for bafilomycin biosynthesis lie leuA and leuB, which encode a sugar-O-methyltransferase and a glycosyltransferase, respectively. LeuA and LeuB are the only enzymes encoded by the genome of Kitasatospora sp. MBT66 that are candidates for the methyl rhamnosylation of natural products, and mutation of leuB abolished glycosylation of both families of natural products. Thus, LeuA and -B mediate the post-PKS methyl-rhamnosylation of bafilomycin A1 to leucanicidin and of phenazines to endophenasides, showing surprising promiscuity by tolerating both macrolide and phenazine skeletons as the substrates. Detailed metabolic analysis by MS/MS based molecular networking facilitated the characterization of nine novel phenazine glycosides 6-8, 16, and 22-26, whereby compounds 23 and 24 represent an unprecedented tautomeric glyceride phenazine, further enriching the structural diversity of endophenasides. PMID- 26675042 TI - Protecting the Health and Well-being of Populations from Disasters: Health and Health Care in The Sendai Framework for Disaster Risk Reduction 2015-2030. AB - The Sendai Framework for Disaster Risk Reduction (DRR) 2015-2030 is the first of three United Nations (UN) landmark agreements this year (the other two being the Sustainable Development Goals due in September 2015 and the climate change agreements due in December 2015). It represents a step in the direction of global policy coherence with explicit reference to health, economic development, and climate change. The multiple efforts of the health community in the policy development process, including campaigning for safe schools and hospitals, helped to put people's mental and physical health, resilience, and well-being higher up the DRR agenda compared with its predecessor, the 2005 Hyogo Framework for Action. This report reflects on these policy developments and their implications and reviews the range of health impacts from disasters; summarizes the widened remit of DRR in the post-2015 world; and finally, presents the science and health calls of the Sendai Framework to be implemented over the next 15 years to reduce disaster losses in lives and livelihoods. PMID- 26675043 TI - Cachexia: a nutritional syndrome? AB - Cachexia leads to nutritional deficits including anorexia and loss of fat and muscle mass. In persons with precachexia or early cachexia, for example, old persons with weight loss and chronic obstructive pulmonary disease, there is strong evidence that nutritional support improves outcomes. Limited evidence suggests that this may be true for heart failure and chronic kidney disease. The evidence for nutritional support in refractory cachexia is, not surprisingly, less dramatic. It would appear that early in the cachectic process, nutrition, coupled with exercise, may be an important therapeutic approach. PMID- 26675044 TI - A continuous kinetic assay for protein and DNA methyltransferase enzymatic activities. AB - BACKGROUND: Methyltransferases (MTs) catalyze the S-adenosylmethionine (SAM) dependent methylation of a wide variety of protein and DNA substrates. Methylation of lysine, arginine or cytosine regulates a variety of biological processes including transcriptional activation and gene silencing. Despite extensive studies of the cellular roles of MTs, their quantitative kinetic characterization remains challenging. In the past decade, several assays have been developed to monitor methyl transfer activity utilizing different approaches including radiolabeling, antibodies or mass-spectrometry analysis. However, each approach suffers from different limitation and no easy continuous assay for detection of MT activity exists. RESULTS: We have developed a continuous coupled assay for the general detection of MTs activity. In this assay, the formation of S-adenosylhomocysteine (SAH) product is coupled NAD(P)H oxidation through three enzyme reactions including glutamate dehydrogenase leading to absorbance changes at 340 nm. The utility and versatility of this assay is demonstrated for SET7/9 and SETD6 with peptides and full length protein substrates and for M.HaeIII with a DNA substrate. CONCLUSIONS: This study shows a simple and robust assay for the continuous monitoring of MT enzymatic activity. This assay can be used for the determination of steady-state kinetic enzymatic parameters (e.g., k cat and K M) for a wide variety of MTs and can be easily adapted for high-throughput detection of MT activity for various applications. PMID- 26675045 TI - New Tools for Characterizing Metallic Nanoparticles: AgNPs, A Case Study. AB - Currently, transmission electron microscopy (TEM) is the main technique for estimating the sizes of spherical nanoparticles (NPs) and through them, their concentrations. This paper demonstrates for the first time that C18 reversed phase capillary liquid chromatography (Cap-LC) coupled to diode array detection (DAD) has the potential to estimate mean concentrations of silver nanoparticles (AgNPs) and thereby determine their average size. Direct injection of the sample without previous extraction or separation steps is carried out. Only a unique standard with a known AgNP size is needed for the calibration. In a first approach, the new method has been tested over silver nanoparticles, produced using different methods of synthesis, and their water dilutions. Good results were achieved: relative errors ranged up to 5% compared with TEM. Also stability and functionality-related NP properties, as well as nonspherical AgNPs, can be studied using this method. Moreover, by coupling online in-tube solid-phase microextraction (IT-SPME) to Cap-LC-DAD, the effect of the dilution can be studied as particles distribute by polarity in two groups, a distribution that responds to average particle size of not only AgNPs, but also gold nanoparticles (AuNPs). In such a distribution, the average particle size is correlated with the peak area ratio. Additionally, besides higher sensitivity and concentration dependent signals, IT-SPME-Cap-LC responds to changes in the particle's hydrodynamic diameter allowing, for instance, the detection of cationic surfactants. Size-exclusion and hydrophobic effects are the mechanisms involved to explain this behavior. PMID- 26675046 TI - Evaluation of fatty acid profile and biodiesel properties of microalga Scenedesmus abundans under the influence of phosphorus, pH and light intensities. AB - The present study dealt with biomass, lipid concentration, fatty acid profile and biodiesel properties of microalga Scenedesmus abundans under different phosphate concentrations, pH and light intensities, one at a time. Among different phosphate concentrations, higher biomass (770.10+/-11.0mg/L) and lipid concentration (176.87+/-4.6mg/L) were at the concentration of 60mg/L. Light intensity at 6000lux yielded higher biomass and lipid concentration of 742.0+/ 9.7 and 243.15+/-9.1mg/L, respectively. The biomass (769.0+/-12.3mg/L) and lipid (179.47+/-5.5mg/L) concentration were highest at pH 8 and pH 6, respectively. All the culture treatments showed marked effect on the fatty acid profile and biodiesel properties of the extracted oil. FAME derived biodiesel properties were compared with European biodiesel standards (EN 14214), Indian biodiesel standards (IS 15607) and American biodiesel standards (ASTM D 6751-08) to assess the suitability of algal oil as biodiesel feedstock. PMID- 26675047 TI - Improving enzymatic saccharification of bamboo shoot shell by alkalic salt pretreatment with H2O2. AB - Pretreatment of bamboo shoot shell (BSS) by a combination of alkalic salts with hydrogen peroxide (H2O2) was evaluated for its delignification effect and for its ability to enhance enzymatic saccharification of pretreated solids. By comparing different alkalic salts, the combination of 9% Na3PO4.12H2O and 0.3g/g H2O2 (ASHP) was identified as an effective system that showed the highest delignification of 87.7% and the total reducing sugar yield of 97.1% when pretreated BSS at a solid to liquid ratio of 1/20 (w/w) at 80 degrees C for 2h. The delignification effect and the disruption of the lignocelluloses structure by this novel pretreatment method were deduced to be the main reasons that led to enhanced enzymatic saccharification as supported by the chemical composition analysis and the results of SEM, FTIR and XRD analyses of the untreated and alkalic salt pretreated BSS. PMID- 26675049 TI - The value of ultrasound in the diagnosis of limited scleroderma - a case report. AB - Systemic sclerosis, popularly referred to as scleroderma, is a chronic connective tissue disease with present autoantibodies against platelet-derived growth factor receptor. These antibodies activate directly fibroblasts causing the dermis and internal organs' fibrosis and vascular damage. Additionally, calcific collections, including hydroxyapatite crystals, may develop in subcutaneous tissue and juxta-articular soft tissue. Herein, we report a case of a 72-year-old woman, referred by a rheumatologist for plain radiography and ultrasound examination of hands due to pain and swelling of the fourth finger of the left hand. Dermal induration affecting hands, especially fourth finger on the left side and the Raynaud phenomenon were observed on physical examination. Furthermore, the patient had noticed periodic discharge with a toothpaste consistency from a tiny fistula localised in the vicinity of the fourth finger alterations. The paper emphasises a possible application of the twinkling artefact and MicroPure option on ultrasound examination in differential diagnosis of soft tissue calcifications. Making the correct diagnosis can attribute to precise planning of surgical treatment. PMID- 26675048 TI - T7 replisome directly overcomes DNA damage. AB - Cells and viruses possess several known 'restart' pathways to overcome lesions during DNA replication. However, these 'bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly. PMID- 26675050 TI - Strategies for Controlling Blood Pressure and Reducing Cardiovascular Disease Risk in Patients with Chronic Kidney Disease. AB - Patients with chronic kidney disease (CKD) suffer from an increased prevalence of cardiovascular disease (CVD) risk factors, and a high rate of premature CV morbidity and mortality. The confluence of CV risk factors, in the context of cardio-metabolic perturbations that vary as renal function declines, complicates strategies for the care of patients with CKD. Understanding the existing evidence for effective CVD treatment strategies can help providers better care for these patients, navigate the complex treatment guidelines, which often differ across major organizations, and minimize the conflicting recommendations that new studies may pose. A pragmatic approach is to target a BP <140/90 mm Hg, which frequently requires more than two or three antihypertensive agents. Most guidelines recommend a combination of diuretic and angiotensin converting enzyme inhibitor or angiotensin receptor blockers, along with a dihydropyridine calcium channel blocker, beta blocker or other agent based on co-existing medical conditions. Consideration for a lower BP goal and/or other therapeutic interventions should be based on the etiology of CKD, stage of CKD, and/or presence of proteinuria. Finally, most patients with CKD, not on dialysis, would benefit from treatment with statins and non-pharmacologic lifestyle interventions should be promoted for all patients with CKD. PMID- 26675051 TI - Evaluation of the Finnish Diabetes Risk Score to predict type 2 diabetes mellitus in a Colombian population: A longitudinal observational study. AB - AIM: To assess the performance of the Finnish Diabetes Risk Score (FINDRISC) questionnaire for detecting and predicting type 2 diabetes mellitus (DM2) in a Colombian population. METHODS: This is a longitudinal observational study conducted in Floridablanca, Colombia. Adult subjects (age >= 35 years) without known diabetes, were included. A modified version of FINDRISC was completed, and the glycemia values from all the subjects were collected from the hospital's database. Firstly, a cross-sectional analysis was performed and then, the subsample of prediabetic participants was followed for diabetes incidence. RESULTS: A total of 772 subjects were suitable for the study. The overall prevalence of undiagnosed DM2 was 2.59%, and the incidence of DM2 among the prediabetic participants was 7.5 per 100 person-years after a total of 265257 person-years follow-up. The FINDRISC at baseline was significantly associated with undiagnosed and incident DM2. The area under receiver operating characteristics curve of the FINDRISC score for detecting undiagnosed DM2 in both men and women was 0.7477 and 0.7175, respectively; and for predicting the incidence of DM2 among prediabetics was 71.99% in men and 67.74% in women. CONCLUSION: The FINDRISC questionnaire is a useful screening tool to identify cross-sectionally unknown DM2 and to predict the incidence of DM2 among prediabetics in the Colombian population. PMID- 26675052 TI - Large Conductance Switching in a Single-Molecule Device through Room Temperature Spin-Dependent Transport. AB - Controlling the spin of electrons in nanoscale electronic devices is one of the most promising topics aiming at developing devices with rapid and high density information storage capabilities. The interface magnetism or spinterface resulting from the interaction between a magnetic molecule and a metal surface, or vice versa, has become a key ingredient in creating nanoscale molecular devices with novel functionalities. Here, we present a single-molecule wire that displays large (>10000%) conductance switching by controlling the spin-dependent transport under ambient conditions (room temperature in a liquid cell). The molecular wire is built by trapping individual spin crossover Fe(II) complexes between one Au electrode and one ferromagnetic Ni electrode in an organic liquid medium. Large changes in the single-molecule conductance (>100-fold) are measured when the electrons flow from the Au electrode to either an alpha-up or a beta down spin-polarized Ni electrode. Our calculations show that the current flowing through such an interface appears to be strongly spin-polarized, thus resulting in the observed switching of the single-molecule wire conductance. The observation of such a high spin-dependent conductance switching in a single molecule wire opens up a new door for the design and control of spin-polarized transport in nanoscale molecular devices at room temperature. PMID- 26675053 TI - The usefulness of ultrasound in the diagnostics of Sjogren's syndrome. AB - Sjogren's syndrome is an autoimmune exocrinopathy which manifests itself with dryness of the eyes and the oral cavity. These symptoms comprise a so-called sicca syndrome (xerostomia and xerophthalmia). Two forms of this disease may be distinguished: primary Sjogren's syndrome which affects salivary glands and secondary Sjogren's syndrome with other autoimmune diseases present such as rheumatoid arthritis, systemic lupus erythematosus or systemic scleroderma. The diagnosis is based on the classification criteria established in 2002 by a group of American and European scientists (American-European Consensus Group), which involve the interview and physical examination as well as serological, histopathological and radiological tests. Most of these examinations show some limitations such as invasiveness, expensiveness or limited accessibility. The latest research suggests that ultrasound examination may appear promising in the diagnostics of the main salivary glands: submandibular and parotid glands. It is an accessible and relatively cheap examination with high sensitivity and specificity values which are comparable to those obtained via conventional means used in the diagnostics of this disease, i.e. biopsy of the minor salivary glands, sialography and scintigraphy, as well as superior to those obtained in sialometry and Schirmer's test. Additionally, ultrasonography correlates with the results of magnetic resonance imaging. Therefore, a number of authors claim that US examination should be included in the classification criteria of Sjogren's syndrome. The aim of this article is to present the diagnostic capacity of the US examination in Sjogren's syndrome using the current ultrasound classification systems based on the grey-scale, Doppler and contrast-enhanced examinations. The latest research confirms that the most valuable diagnostic criterion in Sjogren's syndrome is the heterogeneity of the glandular parenchyma. The outcome of the examination greatly depends on the examiner's experience. PMID- 26675054 TI - Cardiac anomalies in a group of HIV-infected children in a pediatric hospital: an echocardiographic study in Yaounde, Cameroon. AB - BACKGROUND: Cardiac manifestations associated with the HIV infection are known adversely prognosis in adults and children, even at the infraclinical stage. Although cardiac complications of HIV infection are well described in adults, there are few reports in the paediatric age group. We performed echocardiography on a group of HIV-infected children in order to describe the spectrum of the anomalies associated with the HIV infection. METHODS: We carried out a cross sectional descriptive study on a cohort of HIV-infected children followed-up in a children's out-patient clinic. All had a thorough clinical evaluation and transthoracic echocardiography with Doppler flux analysis. The data collected were analyzed with SPPS 18.0, IBM, Chicago. Statistical significance was set at P value <0.05. RESULTS: One hundred children (52 males and 48 females) were studied. Their ages ranged from 1 to 15 years with a mean of 7 years. Forty four (44%) and 33 (33%) of the children were in World Health Organization (WHO) clinical stage III and IV respectively. Fifty seven (57%) did not have any significant immune depression. The mean age at diagnosis of HIV infection was 3 years. Ninety one percent of the participants were on highly active antiretroviral therapies (HAART). At least one cardiac abnormality was found in 89% of the participants; right ventricular (RV) dilatation in 76%, LV diastolic dysfunction in 32%, LV hypertrophy in 12%, pericardial effusion in 11% and LV systolic dysfunction in 2%. These abnormalities were more prevalent in late stages of the infection. CONCLUSIONS: Cardiac abnormalities are frequent in HIV infected children, most of which remain asymptomatic. Routine echocardiography in HIV infected children will aid prompt diagnosis. PMID- 26675055 TI - Comparative study of vaginal danazol vs diphereline (a synthetic GnRH agonist) in the control of bleeding during hysteroscopic myomectomy in women with abnormal uterine bleeding: a randomized controlled clinical trial. AB - OBJECTIVE: To compare the usefulness of vaginal danazol and diphereline in the management of intra-operative bleeding during hysteroscopy. DESIGN: Randomized controlled clinical trial. SETTING: University hospital. PATIENTS: One hundred and ninety participants of reproductive age were enrolled for operative hysteroscopy. Thirty women were excluded from the study. INTERVENTIONS: One hundred and sixty participants with submucous myomas were allocated at random to receive either vaginal danazol (200mg BID, 30 days before surgery) or intramuscular diphereline (twice with a 28-day interval). MAIN OUTCOME MEASURES: Severity of intra-operative bleeding, clarity of the visual field, volume of media, operative time, success rate for completion of operation and postoperative complications. RESULTS: Overall, 145 patients completed the study. In the danazol group, 78.1% of patients experienced no intra-operative uterine bleeding, and 21.9% experienced mild bleeding. In the diphereline group, 19.4% of patients experienced no intra-operative uterine bleeding, but mild, moderate and severe bleeding was observed in 31.9%, 45.8% and 2.8% of patients, respectively. The difference between the groups was significant (p<0.001). A clear visual field was reported more frequently in the danazol group compared with the diphereline group (98.6% vs 29.2%, p<0.001). The mean operative time was 10.9 min and 10.6 min in the danazol and diphereline groups, respectively (p=0.79). The mean volume of infused media was 2.0L in both groups (p=0.99). The success rate was 100% for both groups with no intra-operative complications. CONCLUSION: Both vaginal danazol and diphereline were effective in controlling uterine bleeding during operative hysteroscopy. However, vaginal danazol provided a clearer visual field. PMID- 26675056 TI - Bipolar versus balloon endometrial ablation in the office: a randomized controlled trial. AB - OBJECTIVE: To compare the effectiveness of bipolar radiofrequency (Novasure(r)) ablation and balloon endometrial ablation (Thermablate(r)). STUDY DESIGN: We performed a multi-center double blind, randomized controlled trial in three hospitals in The Netherlands. Women with heavy menstrual bleeding were randomly allocated to bipolar or balloon endometrial ablation, performed in the office, using a paracervical block. The primary outcome was amenorrhea. Secondary outcome measures were pain, satisfaction, quality of life and reintervention. RESULTS: 104 women were randomized into the bipolar (52) and balloon (52) groups. After 12 months amenorrhea rates were 56% (29/52) in the bipolar group and 23% (12/52) in the balloon group (relative risk (RR) 0.6, 95% confidence interval (CI) 0.4-0.8). The mean visual analog pain score of the total procedure was 7.1 in the bipolar group and 7.4 in the balloon group (P<.577). 87% (45/52) of the patients in the bipolar group were satisfied with the result of the treatment versus 69% (36/52) in the balloon group (RR 0.44, 95% CI 0.2-0.97). The reintervention rates were 5/52 (10%) in the bipolar group and 6/52 (12%) in the balloon group (RR 1.02, 95% CI 0.9-1.2). Quality of life (Shaw score) improved over time (P<.001) and was significantly higher in the bipolar group at 12 months follow-up (P=.025). CONCLUSION: In the treatment of heavy menstrual bleeding, bipolar radiofrequency endometrial ablation is superior to balloon endometrial ablation as an office procedure in amenorrhea rate, patient satisfaction and quality of life. PMID- 26675058 TI - Cystic Lesions in Autoimmune Pancreatitis. AB - Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases. PMID- 26675057 TI - Predicting the impact of promoter variability on regulatory outputs. AB - The increased availability of whole genome sequences calls for quantitative models of global gene expression, yet predicting gene expression patterns directly from genome sequence remains a challenge. We examine the contributions of an individual regulator, the ferrous iron-responsive regulatory element, BqsR, on global patterns of gene expression in Pseudomonas aeruginosa. The position weight matrix (PWM) derived for BqsR uncovered hundreds of likely binding sites throughout the genome. Only a subset of these potential binding sites had a regulatory consequence, suggesting that BqsR/DNA interactions were not captured within the PWM or that the broader regulatory context at each promoter played a greater role in setting promoter outputs. The architecture of the BqsR operator was systematically varied to understand how binding site parameters influence expression. We found that BqsR operator affinity was predicted by the PWM well. At many promoters the surrounding regulatory context, including overlapping operators of BqsR or the presence of RhlR binding sites, were influential in setting promoter outputs. These results indicate more comprehensive models that include local regulatory contexts are needed to develop a predictive understanding of global regulatory outputs. PMID- 26675059 TI - Effect of Structured and Unstructured Physical Activity Training on Cognitive Functions in Adolescents - A Randomized Control Trial. AB - BACKGROUND: Regular physical activity in children and adolescents promotes not only their physical health but also improves their cognition. Paper and pencil Neurocognitive tests (NCT) are commonly used to assess the various cognitive domains of a person and can be used as simple tests to assess improvements, if any, in the cognitive abilities of growing adolescents who practice regular physical activity. AIM: To study the effect of six months of structured and unstructured physical activity on cognitive functions in adolescents. MATERIALS AND METHODS: We recruited 439 healthy adolescent volunteers in the age group of 12 to 17 years (boys 250, girls 189) from a residential school (Jawahar Navodaya Vidyalaya, Pondicherry). The following paper and pencil neuropsychological cognitive tests were administered: Two Target Letter Cancellation test, Trail Making test A and B, Ruff Figural Fluency test (RFFT). These participants were then divided into Structured Physical Activity (SPA: n=219; boys 117, girls 102) and Unstructured Physical Activity (USPA: n=220; boys 119, girls 101) groups based on age and gender block randomization method. Six-month intervention was successfully completed by 347 participants only (SPA group: n= 136; boys 77, girls 59; USPA group: n = 139; boys 75, girls 64) and the tests were repeated. STATISTICAL ANALYSIS: The data were recorded and statistically analysed by per protocol analysis method, using the Statistical Package for Social Sciences (SPSS), version 19. RESULTS: After six months of intervention, both SPA and USPA group participants showed significant improvements in all the tested neurocognitive parameters. On inter-group comparison, participants in SPA group showed significantly better improvements. CONCLUSION: Physical activity training in adolescents is more beneficial when structured as per WHO guidelines, probably due to higher cognitive loading. PMID- 26675060 TI - Increasing Therapist Productivity: Using Lean Principles in the Rehabilitation Department of an Academic Medical Center. AB - The Department of Rehabilitation Services, within the University of Maryland Medical Center's 650-bed academic medical center, was experiencing difficulty in meeting productivity standards. Therapists in the outpatient division believed they were not spending enough time performing billable patient care activities. Therapists in the inpatient division had difficulty keeping pace with the volume of incoming referrals. Collectively, these issues caused dissatisfaction among referral sources and frustration among the staff within the rehabilitation department. The department undertook a phased approach to address these issues that included examining the evidence, using Lean process improvement principles, and employing transformational leadership strategies to drive improvements in productivity and efficiency. The lessons learned support the importance of having meaningful metrics appropriate for the patient population served, the use of Lean as an effective tool for improving productivity in rehabilitation departments, the impact of engaging staff at the grassroots level, and the importance of having commitment from leaders. The study findings have implications for not only rehabilitation and hospital leadership, but CEOs and managers of any business who need to eliminate waste or increase staff productivity. PMID- 26675061 TI - Knee Extension Range of Motion at 4 Weeks Is Related to Knee Extension Loss at 12 Weeks After Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: The anterior cruciate ligament (ACL) is commonly torn, and surgical reconstruction is often required to allow a patient to return to their prior level of activity. Avoiding range of motion (ROM) loss is a common goal, but little research has been done to identify when ROM loss becomes detrimental to a patient's future function. PURPOSE: To determine whether there is a relationship between early knee side-to-side extension difference after ACL reconstruction and knee side-to-side extension difference at 12 weeks. The hypothesis was that early (within the first 8 weeks) knee side-to-side extension difference will be predictive of knee side-to-side extension difference seen at 12 weeks. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Knee side-to-side extension difference measures were taken on 74 patients undergoing ACL reconstruction rehabilitation at the initial visit and 4, 8, and 12 weeks postoperatively. Visual analog scores (VAS) and International Knee Documentation Committee (IKDC) scores were also recorded at these time frames. RESULTS: There was a strong relationship between knee extension ROM at 4 and 12 weeks (r = 0.639, P < .001) and 8 and 12 weeks (r = 0.742, P < .001). When the variables of knee extension ROM at initial visit and 4 and 8 weeks were entered into a regression analysis, the predictor variable explained 61% (R (2) = 0.611) of variance for knee extension ROM at 12 weeks, with 4 weeks (R (2) = 0.259) explaining the majority of this variance. CONCLUSION: This study found that a patient's knee extension at 4 weeks was strongly correlated with knee extension at 12 weeks. CLINICAL RELEVANCE: This information may be useful for clinicians treating athletic patients who are anxious for return to sport by providing them an initial goal to work toward in hopes of ensuring successful rehabilitation of their knee. PMID- 26675062 TI - Lung Size and the Risk of Radiation Pneumonitis. AB - PURPOSE: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. METHODS AND MATERIALS: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a function of lung dose and other factors. RESULTS: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. CONCLUSIONS: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis. PMID- 26675063 TI - Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography Based Metrics. AB - PURPOSE: To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. METHODS AND MATERIALS: Eighty five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. RESULTS: Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion >=30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. CONCLUSIONS: Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion >=30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced with anatomic correction methods. PMID- 26675065 TI - Giant Raman Response to the Encapsulation of Sulfur in Narrow Diameter Single Walled Carbon Nanotubes. AB - Encapsulation of sulfur in HiPCO-SWNTs leads to large changes in the Raman spectra with the appearance of new peaks at 319, 395, and 715 cm(-1) which originate from the sulfur species within the SWNTs, while the high frequency SWNT bands (nu > 1200 cm(-1)) are decreased in intensity. The encapsulated species also shifts the near-IR interband electronic transitions to lower energy by more than 10%. These effects seem to originate with the van der Waals interaction of the confined sulfur species with the walls of the SWNTs which are not expected to be significant in the case of the previously studied large diameter SWNTs. We suggest that sulfur in the small diameter SWNTs exists as a helical polymeric sulfur chain that enters the SWNT interior in the form of S2 ((3)Sigma(g)(-)) molecules which undergo polymerization to linear diradicals. PMID- 26675064 TI - A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck. AB - PURPOSE: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5 fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. METHODS AND MATERIALS: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m(2) day 1; cisplatin, 75 mg/m(2) day 1; 5-fluorouracil [5-FU], 750 mg/m(2) day 1-5) and cetuximab, 250 mg/m(2) weekly (loading dose of 400 mg/m(2)). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. RESULTS: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). CONCLUSIONS: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose. PMID- 26675067 TI - Amphibians have immunoglobulins similar to ancestral IgD and IgA from Amniotes. AB - We studied the immunoglobulin genes from either the genomes or RNAs of amphibians. In particular, we obtained data from one frog genome (Nanorana parkeri) and three transcriptomes of the Caudata order (Andrias davidianus, Notophthalmus viridescens and Cynops pyrrhogaster). Apart from the immunoglobulins IgM and IgY previously described, we identified several IgD related immunoglobulins. The species N. parkeri, N. viridescens and C. pyrrhogaster have two IgD genes, while Andrias davidianus has three such genes. The three Caudata species have long IgD immunoglobulins similar to IgD of reptiles, and could be an ancient relic from the common ancestor of IgD of all mammals and reptiles. We also found two IgA isotypes. The results suggest that one of the IgA may be the ancestor of IgA in crocodiles and birds, while the other could be the ancestor IgA found in mammals. These results provide information that could help understand the evolution of immunoglobulins in terrestrial vertebrates. PMID- 26675066 TI - Noninvasive diagnostics of mitochondrial disorders in isolated lymphocytes with high resolution respirometry. AB - BACKGROUND: Mitochondrial diseases belong to the most severe inherited metabolic disorders affecting pediatric population. Despite detailed knowledge of mtDNA mutations and progress in identification of affected nuclear genes, diagnostics of a substantial part of mitochondrial diseases relies on clinical symptoms and biochemical data from muscle biopsies and cultured fibroblasts. METHODS: To investigate manifestation of oxidative phosphorylation defects in isolated lymphocytes, digitonin-permeabilized cells from 48 children were analyzed by high resolution respirometry, cytofluorometric detection of mitochondrial membrane potential and immunodetection of respiratory chain proteins with SDS and Blue Native electrophoreses. RESULTS: Evaluation of individual respiratory complex activities, ATP synthesis, kinetic parameters of mitochondrial respiratory chain and the content and subunit composition of respiratory chain complexes enabled detection of inborn defects of respiratory complexes I, IV and V within 2 days. Low respiration with NADH-dependent substrates and increased respiration with glycerol-3-phosphate revealed complex I defects; changes in p 50 for oxygen and elevated uncoupling control ratio pointed to complex IV deficiency due to SURF1 or SCO2 mutation; high oligomycin sensitivity of state 3-ADP respiration, upregulated mitochondrial membrane potential and low content of complex V were found in lymphocytes with ATP synthase deficiency due to TMEM70 mutations. CONCLUSION: Based on our results, we propose the best biochemical parameters predictive for defects of respiratory complexes I, IV and V manifesting in peripheral blood lymphocytes. GENERAL SIGNIFICANCE: The noninvasiveness, reliability and speed of an approach utilizing novel biochemical criteria demonstrate the high potential of isolated lymphocytes for diagnostics of oxidative phosphorylation disorders in pediatric patients. PMID- 26675069 TI - Expression of DNAM-1 (CD226) on inflammatory monocytes. AB - DNAM-1 is an activating receptor expressed on NK cells and T cells and plays an important role in cytotoxicity of these cells against target cells. Although the role of DNAM-1 in the function of T cells and NK cells has been well studied, the expression and function of DNAM-1 on myeloid cells have been incompletely understood. In this study, we investigated expression of DNAM-1 on monocyte subsets in mouse peripheral blood and found that only inflammatory monocytes (iMos), but not patrolling monocytes (pMos), expressed high levels of DNAM-1. In addition, we found that DNAM-1 was highly expressed on iMos, rather than pMos, also in human. Furthermore, we found that DNAM-1 on inflammatory monocytes was involved in cell adhesion to CD155-expressing cells. Therefore, we propose that expression of DNAM-1 on inflammatory monocytes are evolutionally conserved and act as an adhesion molecule on blood inflammatory monocytes. PMID- 26675068 TI - Anti-complement activity of the Ixodes scapularis salivary protein Salp20. AB - Complement, a major component of innate immunity, presents a rapid and robust defense of the intravascular space. While regulatory proteins protect host cells from complement attack, when these measures fail, unrestrained complement activation may trigger self-tissue injury, leading to pathologic conditions. Of the three complement activation pathways, the alternative pathway (AP) in particular has been implicated in numerous disease and injury states. Consequently, the AP components represent attractive targets for therapeutic intervention. The common hard-bodied ticks from the family Ixodidae derive nourishment from the blood of their mammalian hosts. During its blood meal the tick is exposed to host immune effectors, including the complement system. In defense, the tick produces salivary proteins that can inhibit host immune functions. The Salp20 salivary protein of Ixodes scapularis inhibits the host AP pathway by binding properdin and dissociating C3bBbP, the active C3 convertase. In these studies we examined Salp20 activity in various complement-mediated pathologies. Our results indicate that Salp20 can inhibit AP-dependent pathogenesis in the mouse. Its efficacy may be part in due to synergic effects it provides with the endogenous AP regulator, factor H. While Salp20 itself would be expected to be highly immunogenic and therefore inappropriate for therapeutic use, its emergence speaks for the potential development of a non-immunogenic Salp20 mimic that replicates its anti-properdin activity. PMID- 26675070 TI - Unusual Clinical Presentation of Gastrointestinal Clear Cell Sarcoma. AB - BACKGROUND: Use of molecular assays is gradually becoming a mandatory part of the clinical management of soft tissue tumors, however the choice and the interpretation of these tests may present a challenge. SUMMARY: This report demonstrates an unusual presentation of sarcoma, which was initially diagnosed as a tumor of unknown primary site. Given the presence of vimentin, Fli-1, CD99 and S100 markers, lack of immunostaining for melan A, HMB45, MITF, synaptophysin, CD56, myf4, CKAE1/3 and WT-1, as well as the presence of EWSR1 translocation determined by a break-apart FISH assay, Ewing's sarcoma (ES) diagnosis seemed to be well justified. However, polymerase chain reaction testing for ES-specific rearrangements (EWSR1/FLI1, EWSR1/ERG, EWSR1/ETV1, EWSR1/ETV4, EWS/FEV) failed to confirm the ES origin of the neoplastic tissue. We further considered clinical, morphological, immunohistochemical and molecular diagnostic features of other types of EWSR1-rearranged sarcomas and performed molecular testing for gastrointestinal clear cell sarcoma. The polymerase chain reaction assay revealed EWSR1ex7/ATF1ex5 fusion, thus confirming the latter diagnosis. Subsequent high precision computed tomography of the abdominal cavity revealed a 5-cm tumor of the small bowel, which was subjected to surgical resection. KEY MESSAGE: This report exemplifies that the use of anonymous cytogenetic assays, such as break apart FISH EWSR1 testing, may not be sufficient even in case of a perfect match with relevant morphological and immunohistochemical tumor features. PRACTICAL IMPLICATIONS: Explicit identification of the translocation gene partners is indeed important for proper sarcoma diagnosis management. PMID- 26675071 TI - Cystic Change in Pleomorphic Adenoma: A Rare Finding and a Diagnostic Dilemma. AB - Pleomorphic adenoma forms the majority of salivary gland neoplasms. Cystic change in pleomorphic adenomas is a diagnostic dilemma and can mimic mucoepidermoid carcinoma, mucocele or carcinoma ex pleomorphic adenoma and squamous cell carcinoma. Hereby we report this interesting and rare case of cystic pleomorphic adenoma in a 32-year-old male. PMID- 26675080 TI - Transporter modulation by Chinese herbal medicines and its mediated pharmacokinetic herb-drug interactions. AB - The increasing use of Chinese herbal medicines (CHMs) as complementary therapy and dietary supplement has been greatly raising the concerns about potential herb drug interactions (HDIs). HDIs may cause the augmented or antagonized effects of prescription drugs, resulting in unexpected clinical outcomes. Therefore, it is of significance to identify or predict potential HDIs, and to delineate the underlying mechanisms. Drug transporters play key roles in transmembrane passage of a large number of drugs, affecting their absorption, distribution and elimination. Modulation of drug transporters has been recognized as one of the main causes of HDIs. In the last decade, a growing number of Chinese medicinal herbs and their derived phytochemicals have been identified to have modulatory effect toward transporter proteins, leading to pharmacokinetic HDIs when concomitantly used with conventional drugs. Some of these transporter-mediated interactions have already shown clinical significance. This review article focuses on two major transporter superfamilies, the solute carrier (SLC) and the ATP-binding cassette (ABC) transporters, to provide the recent advanced knowledge on CHMs and their inherent phytochemicals that interact with these transporters, and their induced pharmacokinetic HDIs from both preclinical and clinical aspects. In addition, the challenges and strategy for studying HDIs are also discussed. PMID- 26675081 TI - Randomized Controlled Trial to Evaluate the Efficacy of Oral Dexamethasone and Intramuscular Dexamethasone in Mandibular Third Molar Surgeries. AB - INTRODUCTION: Surgical removal of impacted third molar is the most commonly performed dento-alveolar procedure and is associated with post-operative pain, swelling and trismus. AIM: The aim of the study was to compare the efficacy of dexamethasone administered orally with that of dexamethasone administered as an intra-masseteric injection in surgical removal of mandibular third molars. MATERIALS AND METHODS: Sixty patients with impacted mandibular third molars were selected to undergo surgical removal of mandibular third molars. They were divided into three groups of twenty each, viz., Control Group, Group taking Oral dexamethasone and Group taking Intra-masseteric dexamethasone. Evaluation was done over a period of seven days postoperatively to study the effects of the drug in terms of swelling, trismus and pain. RESULTS: ANOVA test was done and comparisons were made. It was found that there was a statistically significant difference with respect to the group taking oral dexamethasone in terms of resolution of trismus. It was also found that there was no statistical significance with respect to reduction in swelling in either of the groups. CONCLUSION: Thus, it can be concluded that the oral route is superior compared to the intramuscular route when administering dexamethasone in surgical removal of mandibular third molars, with respect to drug dosage, bio-availability and resolution of trismus. PMID- 26675082 TI - Relative Stability of Wild-Type and Mutant p53 Core Domain: A Molecular Dynamic Study. AB - The p53 protein is a stress response protein that functions primarily as a tetrameric transcription factor. A tumor suppressor p53 binds to a specific DNA sequence and transactivates target genes, leading to cell cycle apoptosis. Encoded by the human gene TP53, p53 is a stress response protein that functions primarily as a tetrameric transcription factor. This gene regulates a large number of genes in response to a variety of cellular functions, including oncogene activation and DNA damage. Mutations in p53 are common in human cancer types. Herein we mutate a wild-type p53, 1TSR with four of its mutated proteins. The energy for the wild-type and mutated proteins is calculated by using molecular dynamics simulations along with simulated annealing. Our results show significant differences in energy between hotspot mutations and the wild type. Based on the findings, we investigate the correlation between molar masses of the target residue and the relative energy with respect to the wild type. Our results indicate that the relative energy changes play a pivotal role in bioactivity, in conformity with observations in the rate of mutation in biology. PMID- 26675083 TI - Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain. AB - BACKGROUND: Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB]) in cancer patients with severe neuropathic pain. However, high doses of TB of 140 ug/h are rarely used. PATIENTS AND METHODS: Three cancer patients with severe neuropathic Numeric Rating Scale (NRS) pain scores of 8-10 who were successfully treated with high doses of TB up to 140 ug/h along with other opioids and adjuvant analgesics. RESULTS: TB was administered for a long period of follow-up (9 months to 4 years, including 34-261 days of treatment with the dose of 140 ug/h), which allowed achievement of satisfactory analgesia (NRS 3-5) and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 ug/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment. CONCLUSION: TB at doses of up to 140 ug/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients' quality of life. Clinical studies may explore higher than maximal 140 ug/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. PMID- 26675085 TI - New sonographically-guided test for anterior knee instability - preliminary report. AB - AIM OF THE STUDY: Ultrasound examination is widely used in orthopedic diagnostics, however sonographic evaluation of traumatic anterior cruciate ligament insufficiency is still inadequate. Aim of this study is to evaluate diagnostic capability of a new sonographically-guided test for diagnosing complete anterior cruciate ligament insufficiency. MATERIAL AND METHODS: In 47 patients, with suspicion of unilateral anterior cruciate ligament injury (based on magnetic resonance imaging), the sonographically-guided test for anterior instability was performed. The translation of the intercondylar eminence against the patellar tendon was measured in both knees. Afterwards all patients underwent arthroscopy. RESULTS: In 37 patients, with arthroscopically confirmed complete anterior cruciate ligament insufficiency, the mean anterior knee translation was 8.3 mm (SD = 2.8) in affected knee vs. 3 mm (SD = 1.1) in uninjured knee (p < 0.001). In 10 patients with no anterior cruciate ligament insufficiency the difference between body sides was not significant (2.6 mm, SD = 1.4 in injured knee vs. 2.5 mm, SD = 1.1 in uninjured joint; p < 0.7753). CONCLUSIONS: The proposed test supports the clinician with fast and non-invasive examination that can facilitate evaluation of anterior knee instability. PMID- 26675084 TI - Evolution of cellular morpho-phenotypes in cancer metastasis. AB - Intratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments. VAMPIRE analysis of ~39,000 cells from 13 previously sequenced patient-derived pancreatic cancer samples indicate that metastasized cells present significantly lower heterogeneity than primary tumor cells. We found the same morphological signature for metastasis for a cohort of 10 breast cancer cell lines. We further decipher the relative contributions to heterogeneity from cell cycle, cell-cell contact, cell stochasticity and heritable morphological variations. PMID- 26675086 TI - Different forms of exercise for chronic low back pain (PEDro synthesis). PMID- 26675087 TI - Qualitative review of hazing in collegiate and school sports: consequences from a lack of culture, knowledge and responsiveness. AB - BACKGROUND: As with most mental health disorders, the topic of hazing is not exclusive to the student athlete. However, it is also clear that the unique set of situations faced by athletes create a set of additional and difficult challenges to their mental and physical well-being. A deep-rooted culture, a lack of knowledge about hazing and its causal relationships, and a failure to act by teammates and adults all play a role in the propagation of this danger. Also, in an era where the popular press similarly celebrates and chastises episodes of hazing, it is increasingly crucial to turn to the scientific literature for guidance. PURPOSE: To provide a comprehensive review of the scientific research on hazing in sports and to make recommendations for enhancing the approach and assistance to those in need on an individual and societal level. STUDY DESIGN: Qualitative literature review of hazing in collegiate and school sports. METHODS: Databases including PubMed, Google Scholar, SPORTDiscus, EMBASE and MEDLINE were searched using standardised terms, alone and in combination, including 'hazing', 'bullying', 'sport', 'athlete', 'college', 'school' and 'youth'. FINDINGS: Despite increased attention to its dangers, hazing remains pervasive throughout the sports world. However, many do not recognise those actions as consistent with hazing. A change in culture, increased education and awareness, along with methodologically sound strategies for action must occur in order to reduce the ill effects and cycle of hazing. To date, current information and efforts are lacking. PMID- 26675088 TI - Mental health implications and consequences following sport-related concussion. PMID- 26675089 TI - Short biceps femoris fascicles and eccentric knee flexor weakness increase the risk of hamstring injury in elite football (soccer): a prospective cohort study. AB - BACKGROUND/AIM: To investigate the role of eccentric knee flexor strength, between-limb imbalance and biceps femoris long head (BFlh) fascicle length on the risk of future hamstring strain injury (HSI). METHODS: Elite soccer players (n=152) from eight different teams participated. Eccentric knee flexor strength during the Nordic hamstring exercise and BFlh fascicle length were assessed at the beginning of preseason. The occurrences of HSIs following this were recorded by the team medical staff. Relative risk (RR) was determined for univariate data, and logistic regression was employed for multivariate data. RESULTS: Twenty seven new HSIs were reported. Eccentric knee flexor strength below 337 N (RR=4.4; 95% CI 1.1 to 17.5) and possessing BFlh fascicles shorter than 10.56 cm (RR=4.1; 95% CI 1.9 to 8.7) significantly increased the risk of a HSI. Multivariate logistic regression revealed significant effects when combinations of age, history of HSI, eccentric knee flexor strength and BFlh fascicle length were explored. From these analyses the likelihood of a future HSI in older athletes or those with a HSI history was reduced if high levels of eccentric knee flexor strength and longer BFlh fascicles were present. CONCLUSIONS: The presence of short BFlh fascicles and low levels of eccentric knee flexor strength in elite soccer players increases the risk of future HSI. The greater risk of a future HSI in older players or those with a previous HSI is reduced when they have longer BFlh fascicles and high levels of eccentric strength. PMID- 26675090 TI - Ectopic Supernumerary Tooth at the Anterior Nasal Spine- A Developmental Glitch. PMID- 26675091 TI - The Role of Parafibromin, Galectin-3, HBME-1, ?and Ki-67 in the Differential Diagnosis of Parathyroid Tumors. AB - OBJECTIVES: Parathyroid carcinoma (PC) is a rare parathyroid tumor compared to parathyroid adenoma (PA) and atypical parathyroid adenoma (APA). Recent studies have suggested parafibromin has a role in the differential diagnosis of parathyroid tumors. We sought to determine the role of parafibromin as well as galectin-3, Ki-67, and HBME-1 as diagnostic markers in the differential diagnosis of parathyroid tumors. METHODS: A total of 92 cases diagnosed with PA, APA, or PC at Sifa University and Private Ege Pathology Laboratory between 2006-2012 were included in the study. Parafibromin (microarray), galectin-3, Ki-67, and HBME-1 were evaluated using immunohistochemistry in all parathyroid tumors. RESULTS: Eighty-four cases were diagnosed with PA, six with APA, and two with PC. The study group consisted of 82 females and 10 males. Their mean age was 50.9 years, and the mean tumor diameter was 1.97 cm. Parafibromin was negative in the two PC cases but positive in all APA and PA cases. Positivity was observed with galectin 3 in 17 adenoma cases, three atypical adenomas, and two carcinoma cases. Positivity with HBME-1 was found in 26 PA cases and one PC case. Parafibromin and galectin-3 expression was significant between the three tumor groups but not for HBME-1 expression. Parafibromin expression increased in PA whereas galectin-3 expression decreased. A statistical significance was found between the three tumor groups according to the Ki-67 score (p=0.010). Additionally, the Ki-67 proliferation index was under 1% in PAs. CONCLUSION: The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki 67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors. PMID- 26675092 TI - Knowledge of carbohydrate counting and insulin dose calculations in paediatric patients with type 1 diabetes mellitus. AB - BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) who are able to adjust their insulin doses according to the carbohydrate content of a meal, as well as their blood glucose, are likely to have improved glycaemic control (Silverstein et al., 2005). With improved glycaemic control, patients have a lower risk of developing long-term microvascular complications associated with T1DM (Diabetes Control and Complications Trial Research Group, 1993). To assess the carbohydrate and insulin knowledge of patients attending our paediatric diabetes clinic at the University Hospital Limerick (UHL), the validated PedCarbQuiz (PCQ) was applied to our clinic population. METHODS: This study was completed by applying a questionnaire called the PedCarbQuiz (PCQ) to children exclusively attending our paediatric diabetes clinic at UHL. Of the clinic's 220 patients, 81 participated in the study. RESULTS: The average total PCQ score (%) was higher in the continuous subcutaneous insulin infusion (CSII) group compared with the multiple daily insulin (MDI) injection user group (79.1 +/- 12.1 versus 65.9 +/- 6.6 p = 0.005). The CSII group also had a higher average carbohydrate score (%) compared with the MDI group (79.4 +/- 12.4 versus 66.3 +/- 16.2, p = 0.004). CONCLUSIONS: This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is better among patients treated with CSII compared with MDI. However, knowledge in both groups is poorer than in the original US sample. GENERAL SIGNIFICANCE: This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is poorer than in a US based sample, although this knowledge is better among patients treated with CSII compared with MDI. This highlights the need for improved resources for diabetes and carbohydrate counting education for patients with T1DM. PMID- 26675094 TI - Answer to the question page 508. PMID- 26675093 TI - Endoscopy vs surgery in the treatment of early gastric cancer: Systematic review. AB - AIM: To report a systematic review, establishing the available data to an unpublished 2a strength of evidence, better handling clinical practice. METHODS: A systematic review was performed using MEDLINE, EMBASE, Cochrane, LILACS, Scopus and CINAHL databases. Information of the selected studies was extracted on characteristics of trial participants, inclusion and exclusion criteria, interventions (mainly, mucosal resection and submucosal dissection vs surgical approach) and outcomes (adverse events, different survival rates, mortality, recurrence and complete resection rates). To ascertain the validity of eligible studies, the risk of bias was measured using the Newcastle-Ottawa Quality Assessment Scale. The analysis of the absolute risk of the outcomes was performed using the software RevMan, by computing risk differences (RD) of dichotomous variables. Data on RD and 95%CIs for each outcome were calculated using the Mantel-Haenszel test and inconsistency was qualified and reported in chi(2) and the Higgins method (I (2)). Sensitivity analysis was performed when heterogeneity was higher than 50%, a subsequent assay was done and other findings were compiled. RESULTS: Eleven retrospective cohort studies were selected. The included records involved 2654 patients with early gastric cancer that filled the absolute or expanded indications for endoscopic resection. Three-year survival data were available for six studies (n = 1197). There were no risk differences (RD) after endoscopic and surgical treatment (RD = 0.01, 95%CI: -0.02-0.05, P = 0.51). Five-year survival data (n = 2310) showed no difference between the two groups (RD = 0.01, 95%CI: -0.01-0.03, P = 0.46). Recurrence data were analized in five studies (1331 patients) and there was no difference between the approaches (RD = 0.01, 95%CI: -0.00-0.02, P = 0.09). Adverse event data were identified in eight studies (n = 2439). A significant difference was detected (RD = -0.08, 95%CI: -0.10--0.05, P < 0.05), demonstrating better results with endoscopy. Mortality data were obtained in four studies (n = 1107). There was no difference between the groups (RD = -0.01, 95%CI: -0.02-0.00, P = 0.22). CONCLUSION: Three-, 5-year survival, recurrence and mortality are similar for both groups. Considering complication, endoscopy is better and, analyzing complete resection data, it is worse than surgery. PMID- 26675095 TI - Is Hydroxyethyl Starch Irrelevant to Hemostasis in Patients Undergoing Liver Transplantation?--In vitro Analysis Based on Thromboelastometry. AB - BACKGROUND: Liver transplantation may be associated with severe bleeding that requires intensive fluid management. Aggressive fluid administration could result in hemodilution, triggering dilutional coagulopathy that intensifies bleeding. Colloids are plasma expanders used in daily practice. Fibrinogen, malfunctioning in liver cirrhosis, is the earliest decreasing clotting factor while bleeding. Fibrinogen supplementation is recommended as the first-choice therapy in such cases. Therefore, the influence of hemodilution on fibrin clot formation among patients with liver cirrhosis was analyzed, followed by the assessment of fibrinogen supplementation in clot restitution. MATERIAL AND METHODS: Blood collected from 22 patients with post-inflammatory liver cirrhosis was diluted up to 30% and 60% with crystalloid (0.9% NaCl) or colloid (6% hydroxyethyl starch 130/0.4), followed by fibrinogen supplementation corresponding to an overall dose of 4 g. The influence of hemodilution on plasma fibrinogen concentration and on thromboelastometry FIBTEM test was analyzed, as well as the influence of fibrinogen supplementation. RESULTS: Hemodilution lowers fibrinogen concentration and decreases fibrin clot formation. The higher the grade of dilution, the more profound the disturbances observed; 6% hydroxyethyl starch 130/0.4 cause more intense effect on fibrin clot formation than 0.9% NaCl. Fibrinogen supplementation improves fibrin clot formation as assessed in FIBTEM. CONCLUSIONS: Fibrinogen supplementation among patients with liver cirrhosis might improve fibrin clot formation during hemodilution. Fibrinogen supplementation might by considered as a possible treatment of coagulopathy during liver transplantation, but further clinical studies need to be performed. PMID- 26675096 TI - [Aging well]. PMID- 26675097 TI - [Pain management in subarachnoid hemorrhages]. AB - Pain and anxiety are among the recurring complaints in patients with a subarachnoid haemorrhage. A team assessed the efficacy and quality of pain management in a clinical neuroradiology unit. A global pain management procedure, including antalgic drug protocols and recommendations, was then put in place. PMID- 26675098 TI - [Visual materials for the education of patients with diabetes]. AB - Some people living with diabetes are not included in any educational approach due to their cultural or linguistic particularities, their level of elementary education or their metacognitive deficiencies. It is essential for the caregiver to reflect on how to provide adapted and relevant therapeutic education to these patients. In this context, visual materials have been designed in order to be able to offer personalised support. PMID- 26675099 TI - [Ethics or the quest for the best]. PMID- 26675100 TI - [Foundations and construction of the ethical approach in nursing practice]. AB - The evolution of science and our society raises ethical questions in medical and nursing practice. These give rise to the requirement for individual and collective reflection in order to consider the consequences of decisions and to judge on sometimes complex choices. This reflection concerns both nursing practices and the organisation of the health system. PMID- 26675101 TI - [Nursing care: an ethical act]. AB - Care means taking care, paying extreme attention to others in vulnerable situations, "helping and not hurting". Admitting that ethical care exists would require recognizing that there are also treatments which are not ethical. However, care can only be ethical. PMID- 26675102 TI - [Bioethics, science and conscience]. AB - Both object of science and conscience, bioethics is concerned about the impact of biomedical research and its applications for the human person. Object of pluralistic and multidisciplinary thought and proposal, bioethics seeks to reconcile respect for fundamental values and progress in life sciences. PMID- 26675103 TI - [Bioethics in the Council of Europe]. AB - The Council is an intergovernmental institution that actively defends human rights in biomedicine through its experts' Committee on Bioethics. The field of biomedical science and technology is in constant development. Bioethics provisions must take account. PMID- 26675104 TI - [The local ethics committee, an opportunity for the hospital?]. AB - Meeting both a legal obligation and a motivation of professionals to lead an ethical reflection about the complex issues of their activities, the local ethics committee is based on exchange, listening and collegiality. It gives to everyone a real resource for its own exercise and collective contribution to the quality of care. PMID- 26675105 TI - [Thinking ethics education]. AB - Ethics emerges in the interstices of deontology, in difficult situations generating internal conflicts for the caregiver, sources of anxiety and questioning. Ethics education has always played a major in nursing programs by initiating a reflection on human values. Faced with current uncertainties in the context of care, it is now based on the appropriation of a reflexive approach to the meaning of action. PMID- 26675106 TI - [The student nurse faced with ethical dilemmas]. AB - Although student nurses are taught ethics, the theoretical dimension is not enough. Students must be given support and guidance in their practice to enable them to carry out ethical reflection and to adapt their nursing approach. PMID- 26675107 TI - [The decision to withhold and withdraw active treatments, an ethical approach]. AB - Intensive care medicine is confronted with situations of suffering and dependence experienced as the appropriation of the body or medical futility. In this context, withholding and withdrawing active intensive care must be given a framework. The ethical challenge is to decide to continue or not with care considered vain or futile. The "Leonetti Law", in particular, helps to clarify the situation for professionals and families. PMID- 26675108 TI - [The ethical concerns of the private practice nurse]. AB - Ethics, by its definition, is a philosophical discipline which enables human beings to behave, to act and to be, in the best way possible, between themselves and towards their environment. In private nursing practice, the ethical dimension is based on personal reflection which enables each individual to adapt their attitude in order to act for the best. PMID- 26675110 TI - [Ethical issues "impertinent" hospital business]. PMID- 26675109 TI - [The ethical reflection approach in decision-making processes in health institutes]. AB - Except in the specific case of end-of-life care, the law says nothing about the way in which health professionals must carry out ethical reflection regarding the treatment of their patients. A problem-solving methodology called the "ethical reflection approach" performed over several stages can be used. The decision making process involves the whole team and draws on the ability of each caregiver to put forward a reasoned argument, in the interest of the patient. PMID- 26675111 TI - [Cooperation protocols, state and perspectives]. PMID- 26675112 TI - Targeting cyst wall is an effective strategy in improving the efficacy of marketed contact lens disinfecting solutions against Acanthamoeba castellanii cysts. AB - Acanthamoeba cysts are highly resistant to contact lens disinfecting solutions. Acanthamoeba cyst wall is partially made of 1,4 beta-glucan (i.e., cellulose) and other complex polysaccharides making it a hardy shell that protects the resident amoeba. Here, we hypothesize that targeting the cyst wall structure in addition to antiamoebic compound would improve the efficacy of marketed contact lens disinfecting solutions. Using chlorhexidine as an antiamoebic compound and cellulase enzyme to disrupt cyst wall structure, the findings revealed that combination of both agents abolished viability of Acanthamoeba castellanii cysts and trophozoites. When tested alone, none of the agents nor contact lens disinfecting solutions completely destroyed A. castellanii cysts and trophozoites. The absence of cyst wall-degrading enzymes in marketed contact lens disinfecting solutions render them ineffective against Acanthamoeba cysts. It is concluded that the addition of cyst wall degrading molecules in contact lens disinfecting solutions will enhance their efficacy in decreasing the incidence of Acanthamoeba effectively. PMID- 26675113 TI - Simultaneous determination of CRP and D-dimer in human blood plasma samples with White Light Reflectance Spectroscopy. AB - A dual-analyte assay for the simultaneous determination of C-reactive protein (CRP) and D-dimer in human blood plasma based on a white light interference spectroscopy sensing platform is presented. Measurement is accomplished in real time by scanning the sensing surface, on which distinct antibody areas have been created, with a reflection probe used both for illumination of the surface and collection of the reflected interference spectrum. The composition of the transducer, the sensing surface chemical activation and biofunctionalization procedures were optimized with respect to signal magnitude and repeatability. The assay format involved direct detection of CRP whereas for D-dimer a two-site immunoassay employing a biotinylated reporter antibody and reaction with streptavidin was selected. The assays were sensitive with detection limits of 25ng/mL for both analytes, precise with intra- and inter-assay CV values ranging from 3.6% to 7.7%, and from 4.8% to 9.5%, respectively, for both assays, and accurate with recovery values ranging from 88.5% to 108% for both analytes. Moreover, the values determined for the two analytes in 35 human plasma samples were in excellent agreement with those received for the same samples by standard diagnostic laboratory instrumentation employing commercial kits. The excellent agreement of the results supported the validity of the proposed system for clinical application for the detection of multiple analytes since it was demonstrated that up to seven antibody areas can be created on the sensing surface and successfully interrogated with the developed optical set-up. PMID- 26675114 TI - Comparisons of Pathological Responses in Carrot to Root-knot Nematodes. AB - Carrot (Dacus carota var. sativus) is one of the top-ten most economically important vegetable crops produced worldwide, and the root-knot nematodes, Meloidogyne spp., are one of the most important pests in the carrot. In Korea, M. hapla and M. incognita are presumed to be the major root-knot nematodes distributing mostly in open carrot fields and greenhouses, respectively. In our study, currently-developed and commercial carrot cultivars and the parental lines were examined for their pathological responses to M. incognita and M. hapla 7 weeks after inoculation with about 1,000 second-stage juveniles (J2) of the nematodes. All the carrot cultivars and lines showed susceptible responses to both nematodes with the gall index (GI) of 2.4-4.4, which were always higher on the carrot plants infected with M. incognita than M. hapla. Gall sizes were remarkably larger with more serious reduction of the root growths in the plants infected with M. incognita than M. hapla, suggesting the carrot lines examined in our study were more susceptible to the former than the latter. In the infection sites of the root tissues, giant cells were more extensively formed, occupying larger stellar regions with the prominent destruction of adjacent xylem vessels by M. incognita than M. hapla. All of these results suggest M. incognita affect more seriously on the carrot plants that are grown in greenhouses, compared to M. hapla that has a major distribution in open carrot fields, which would be used for determining cropping systems based on target nematode species, their damage and pathological characteristics. PMID- 26675115 TI - Tetracyanobutadiene functionalized ferrocenyl BODIPY dyes. AB - Tetracyanobutadiene (TCBD) derivatives of ferrocenyl BODIPYs 2a-2c were designed and synthesized by [2 + 2] cycloaddition-retroelectrocyclization reaction of tetracyanoethylene (TCNE) with meso alkynylated ferrocenyl BODIPYs. The TCBD substituted ferrocenyl BODIPYs were designed in such a way that the distance between the ferrocenyl unit and the TCBD remains constant, whereas the distance between the BODIPY and the TCBD unit varies. The TCBD and BODIPY units were connected directly through a single bond (in 2a), through a phenylacetylene linkage (in 2b) and through a vinyl linkage (in 2c). The photonic and electrochemical properties of ferrocenyl BODIPYs were strongly perturbed by the incorporation of TCBD. The TCBD derivatives 2a-2c show red shifted absorption compared to their precursors 1a-1c. The single crystal structures of TCBD functionalized ferrocenyl BODIPYs 2a and 2c reveal extensive intermolecular hydrogen bonding but lack pi-pi stacking interactions. PMID- 26675116 TI - Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes. AB - The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 MUg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 MUg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR. PMID- 26675117 TI - Heart failure in nursing home residents; a cross-sectional study to determine the prevalence and clinical characteristics. AB - BACKGROUND: Heart failure (HF) is expected to be highly prevalent in nursing home residents, but precise figures are scarce. The aim of this study was to determine the prevalence of HF in nursing home residents and to get insight in the clinical characteristics of residents with HF. METHODS: The study followed a multi-centre cross-sectional design. Nursing home residents (n = 501) in the southern part of the Netherlands aged over 65 years and receiving long-term somatic or psychogeriatric care were included in the study. The diagnosis of HF and related characteristics were based on data collected from actual clinical examinations (including history, physical examination, ECG, cardiac markers and echocardiography), patient records and questionnaires. A panel of two cardiologists and a geriatrician ultimately judged the data to diagnose HF. RESULTS: The overall prevalence of HF in nursing home residents was 33 %, of which 52 % had HF with preserved ejection fraction. The symptoms dyspnoea and oedema and a cardiac history were more common in residents with HF. Diabetes mellitus, chronic obstructive pulmonary disease (COPD) were also more prevalent in those with HF. Residents with HF had a higher score on the Mini Mental State Examination. 54 % of those with HF where not known before, and in 31 % with a history of HF, this diagnosis was not confirmed by the expert panel. CONCLUSION: This study shows that HF is highly prevalent in nursing home residents with many unknown or falsely diagnosed with HF. Equal number of HF patients had reduced and preserved left-ventricular ejection fraction. TRIAL REGISTRATION: The Netherlands National Trial Register NTR2663 (27-12-2010). PMID- 26675118 TI - Breast ultrasound scans - surgeons' expectations. AB - Recent years have witnessed a dynamic development of mammary gland imaging techniques, particularly ultrasonography and magnetic resonance imaging. A challenge related to these studies is the increase in the precision of the anatomical assessment of breast, particularly for early detection of subclinical lesions, performance of ultrasound- guided biopsy procedures, and accurate preoperative location of pathological lesions so as to optimize the surgical treatment. Ultrasound imaging is a primary and baseline diagnostic procedure the patient with suspected pathological lesions within breast is referred to by the surgeon. Lesions visualized in ultrasound scans are classified according to the BI-RADS US assessment categories. The successive categories (2 through 6) encompass individual pathological lesions, estimating the risk of malignancy and provide guidelines for further diagnostic and therapeutic management. This article described the important aspects of ultrasonographic imaging of focal lesions within the breasts as significant from the standpoint of surgical treatment of patients falling within BI-RADS US categories 3, 4, 5, and 6. Attention is drawn to the importance of ultrasound scans in the assessment of axillary fossa lymph nodes before the decision regarding the surgical treatment. PMID- 26675119 TI - Thanatophoric Dysplasia: A Case Report. AB - Thanatophoric Dysplasia (TD) is a congenital, sporadic and the most lethal skeletal dysplasia caused by new mutation in the FGFR3 gene. At birth, it is characterized by shortening of the limbs (micromelia), small conical thorax, platyspondyly (flat vertebral bodies) and macrocephaly. TD is divided into two clinically defined subtypes: type I and II with some clinical overlap between the two subtypes. They can be differentiated by the skull shape and femur morphology. Ultrasound examination in the second trimester is often straight forward in diagnosing the congenital anomaly. We report a case of pre term fresh stillborn baby with dysmorphic facies, macrocephaly, micromelia with short stubby fingers and deep skin creases, narrow thorax and protuberant abdomen which delivered at our hospital. The ultrasound examination showed shortening of long bones with femur shaped like telephone receiver. Dysmorphic facial features and skeletal abnormalities in the baby lead us to make the diagnosis of TD type I. Because of the rarity of this condition we report this case of thanatophoric dysplasia with a short review of literature. PMID- 26675120 TI - Test Re-Test Reliability and Validity of Different Visual Acuity and Stereoacuity Charts Used in Preschool Children. AB - BACKGROUND: Preschool vision screenings are cost effective ways to detect children with vision impairments. The use of any vision tests in children must be age appropriate, testable, repeatable and valid. AIM: To compare the test re-test reliability, sensitivity and specificity of different visual acuity and stereo acuity charts used in preschool children. MATERIALS AND METHODS: Monocular visual acuity of 90 subjects (180 eyes) of age 36 to 71 months was assessed with HOTV, Lea and E-chart in a preschool located in a semi urban area, Manipal, Karnataka. After the vision assessment, stereo acuity was recorded using Frisby and Titmus stereo charts followed by comprehensive eye examination. Repeated measurements of visual acuity and stereo acuity were done one week after the initial assessment. RESULTS: Mean age of children was 53+/- 10 months with equal gender distribution. Intra class correlation (ICC) of Lea, HOTV, E-chart, Frisby and Titmus charts were 0.96, 0.99, 0.92, 1.0 and 1.0 respectively. The area under receiver operating curve (ROC) for Lea and E-chart was 0.892 and 0.776. HOTV was considered as the gold standard as it showed the least difference on repeated measurements. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of E-chart was 99, 15, 45, 94 and 21.8 percent, and Lea was 93, 56, 59 and 92 percent. The sensitivity, specificity, PPV and NPV of Frisby was 75, 27, 9, 92 percent were as of Titmus was 75, 13, 8 and 85 percent respectively. CONCLUSION: HOTV chart can be used as the gold standard for measuring visual acuity of pre-schoolers in a semi urban area. Lea chart can be used in the absence of HOTV chart. Frisby and Titmus charts are good screening tools, but with poor diagnostic criteria. PMID- 26675121 TI - Stimulation of laccases from Trametes pubescens: Use in dye decolorization and cotton bleaching. AB - The production of laccases from Trametes pubescens was investigated along with the role of nutrients and elicitors. Copper proved to be a fundamental inducer, although productivity yields were consistently enhanced only in the presence of additional compounds (textile dyes). Using a central composite design, the optimal culture condition was examined, by taking into consideration the three distinct variables and their combinatorial effect. The 290 U ml(-1) of laccases were produced after setting nitrogen, copper, and reactive blue 19 concentration; in a bioreactor, activity recovery was lower (90 U ml(-1)) and pellet morphology was different. The activity of the laccase crude extract was maximal at 60 degrees C and stable for 14 h at 50 degrees C and for 2 months at pH 6 and room temperature. The biotechnological potential was assessed, confirming the capacity to decolorize single or mixed solutions of textile dyes and to enhance the whitening yield of raw cotton fibers, working in synergism with the conventional H2O2-based method. PMID- 26675122 TI - Radial sesamoid fracture of the second MCP joint - a case report. AB - A fracture of the sesamoid bone of the hand is rarely seen. In most cases, it is strictly associated with the trauma. The patient complains of a long-lasting, due to unclear diagnosis, painful swelling of the joint with an inability to flex the affected finger. Limited blood supply makes the untreated fracture prone to avascular necrosis. Thus, it is extremely important to make a proper diagnosis early. Bilateral comparing the affected areas with ultrasonography seems to be the method of choice. The treatment is conservative or surgical when needed. We present a case of a radial sesamoid fracture of the second metacarpophalangeal joint without a history of trauma. PMID- 26675123 TI - Teaching residents screening, brief intervention, and referral to treatment (SBIRT) skills for alcohol use: Using chart-stimulated recall to assess curricular impact. AB - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) improves identification and intervention for patients at risk for developing an alcohol use disorder (AUD). Residency curriculum is designed to teach SBIRT skills, but resources are needed to promote skill implementation. The electronic health record (EHR) can facilitate implementation through integration of decision support tools. The authors developed electronic tools to facilitate documentation of alcohol assessment and brief intervention and to reinforce skills from an SBIRT curriculum. This prospective cohort study assessed primary care internal medicine residents' use of SBIRT skills and EHR tools in practice using chart stimulated recall (CSR). METHODS: Postgraduate year 2 and 3 residents received a 5-hour SBIRT curriculum with skills practice and instruction on SBIRT electronic tools. Participants were then given a list of their patients seen in a 1-year period who were drinking at/above the recommended limit. Trainees selected 3 patients to review with a faculty member in a CSR. Faculty used a 24-item chart checklist to assess application of SBIRT skills and electronic tool use and met with residents to complete a CSR interview. CSR interview notes were analyzed qualitatively to understand application of SBIRT skills and EHR tool use. RESULTS: Eighteen of 20 residents participated in the CSR, and 5 faculty reviewed 46 patient charts. Residents documented alcohol use (84.2% of charts) and assessment of quantity/frequency of use (71.0%) but were less likely to document assessment for an AUD (34%), an appropriate plan (50.0%), or follow-up (55%). Few residents used EHR tools. Residents reported barriers in addressing alcohol use, including lack of knowledge, patient barriers, and time constraints. CONCLUSIONS: More intensive training in SBIRT with opportunities for practice and feedback may be necessary for residents to consistently apply SBIRT skills in practice. EHR tools need to be better integrated into the clinic workflow in order to be useful. PMID- 26675124 TI - A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan. AB - Although development of nanomedicines has been a promising direction in tumor treatment, the therapeutic outcome of current nanomedicines is unsatisfying, partly because of the poor retention and penetration in tumors. Recently, a kind of tumor microenvironment sensitive size shrinkable nanoparticles (DOX-AuNPs GNPs) has been developed by our lab, which could enhance the tumor penetration and retention depending on the size shrinking. However, the further enhancement is still restricted by dense collagen network in tumors. Thus in this study, we combined DOX-AuNPs-GNPs with losartan to deplete tumor collagen (constituted up to 90% of extracellular matrix) to further improve tumor penetration. In vitro, DOX-AuNPs-GNPs can shrink from over 117.8nm to less than 50.0nm and release DOX AuNPs under the triggering of tumor overexpressed matrix metalloproteinases-2 (MMP-2). In vivo, pretreatment with losartan significantly decrease the collagen level and improve the tumor penetration. In combination, losartan combined with DOX-AuNPs-GNPs showed the best drug delivery efficiency, striking penetration efficiency and best 4T1 breast tumor inhibition effect. In conclusion, this study provided a promising synergetic strategy to improve the tumor treatment efficiency of nanomedicines. STATEMENT OF SIGNIFICANCE: We have developed a dual strategy for deep tumor penetration through combining size shrinkable DOX-AuNPs GNPs with depleting tumor collagen by losartan. Additionally, we demonstrate therapeutic efficacy in breast tumor bearing mouse model. DOX-AuNPs-GNPs co administration with losartan is a novel and highly attractive strategy for anti tumor drug delivery with the potential for broad applications in clinic. PMID- 26675125 TI - The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue. AB - The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R(2)=0.885, p<0.001). STATEMENT OF SIGNIFICANCE: This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment. PMID- 26675127 TI - Direct surface visualization of biofilms with high spin coordination clusters using Magnetic Resonance Imaging. AB - Magnetic Resonance Imaging is a powerful tool for the investigation of a biofilms' physical structure determining mass transport behavior which is of major importance in biofilm research. The entire biofilm is imaged in situ non invasively and non-destructively on a meso-scale. In this study, different contrast agents were applied to study the biofilm's properties with the focus on mass transport, which is achieved by varying the contrast agents with respect to their NMR and interaction properties. The spatio-temporal tracking of these cluster, molecular and particulate contrast agents in biofilms was achieved by T1 , T2-weighted and proton density images during short (20h) and long (14 d) term exposures. The best biofilm surface visualization was observed when applying a new high spin coordination cluster (Fe10Gd10) showing a high affinity to the biofilm's surface and a fast immobilization within minutes. Contrarily, the small molecular contrast agents show no immobilization and fully penetrated into the biofilm. A concentration equilibrium was observed which was confirmed in back diffusion experiments. Interactions between larger nanoparticulate contrast agents and the biofilm required hours to achieve immobilization. Thus, the penetration depth into the biofilm is predominantly size-dependent. Here, it is shown that biofilm surface interactions can be observed in situ and spatio temporarily resolved. The reported methodology demonstrates a new means to explore mass transfer of various substances in biofilms. STATEMENT OF SIGNIFICANCE: In biofilm research, the investigation of the biofilms' physical structure is of high relevance for the understanding of mass transport processes. However, commonly used imaging techniques for biofilm imaging such as CLSM or electron microscopy rarely visualize the real biofilm due to their invasiveness and destructiveness. Magnetic Resonance Imaging (MRI) represents the ideal tool to image the biofilm in situ, non-invasively and non-destructively with a spatial resolution of several 10MUm. To gain specific structural and functional information, a variety of MRI contrast agents (molecular and particulate) was applied with different properties for the first time. Results elucidate the interactions between the biofilms' surface and the contrast agents and open a new field for biotechnological applications by functional contrast enhancement. PMID- 26675126 TI - Titanium surface characteristics, including topography and wettability, alter macrophage activation. AB - Biomaterial surface properties including chemistry, topography, and wettability regulate cell response. Previous studies have shown that increasing surface roughness of metallic orthopaedic and dental implants improved bone formation around the implant. Little is known about how implant surface properties can affect immune cells that generate a wound healing microenvironment. The aim of our study was to examine the effect of surface modifications on macrophage activation and cytokine production. Macrophages were cultured on seven surfaces: tissue culture polystyrene (TCPS) control; hydrophobic and hydrophilic smooth Ti (PT and oxygen-plasma-treated (plasma) PT); hydrophobic and hydrophilic microrough Ti (SLA and plasma SLA), and hydrophobic and hydrophilic nano-and micro-rough Ti (aged modSLA and modSLA). Smooth Ti induced inflammatory macrophage (M1-like) activation, as indicated by increased levels of interleukins IL-1beta, IL-6, and TNFalpha. In contrast, hydrophilic rough titanium induced macrophage activation similar to the anti-inflammatory M2-like state, increasing levels of interleukins IL-4 and IL-10. These results demonstrate that macrophages cultured on high surface wettability materials produce an anti-inflammatory microenvironment, and this property may be used to improve the healing response to biomaterials. STATEMENT OF SIGNIFICANCE: Metals like titanium (Ti) are common in orthopaedics and dentistry due to their ability to integrate with surrounding tissue and good biocompatibility. Roughness- and wettability-increasing surface modifications promote osteogenic differentiation of stem cells on Ti. While these modifications increase production of osteoblastic factors and bone formation, little is known about their effect on immune cells. The initial host response to a biomaterial is controlled primarily by macrophages and the factors they secrete in response to the injury caused by surgery and the material cues. Here we demonstrate the effect of surface roughness and wettability on the activation and production of inflammatory factors by macrophages. Control of inflammation will inform the design of surface modification procedures to direct the immune response and enhance the success of implanted materials. PMID- 26675128 TI - A mechanistic study of the interaction of water-soluble borate glass with apatite bound heterocyclic nitrogen-containing bisphosphonates. AB - Long-term oral and intravenous use of nitrogen-containing bisphosphonates (N-BPs) is associated with osteonecrosis of the jaw. Although N-BPs bind strongly to bone surfaces via non-covalent bonds, it is possible for extrinsic ions to dissociate bound N-BPs from mineralized bone by competitive desorption. Here, we investigate the effects and mechanism of using an ionic cocktail derived from borate bioactive glass for sequestration of heterocyclic N-BPs bound to apatite. By employing solid-state and solution-state analytical techniques, we confirmed that sequestration of N-BPs from bisphosphonate-bound apatite occurs in the presence of the borate-containing ionic cocktail. Simulations by density functional theory computations indicate that magnesium cation and borate anion are well within the extent of the risedronate or zoledronate anion to form precipitate complexes. The sequestration mechanism is due to the borate anion competing with bisphosphonates for similar electron-deficient sites on the apatite surface for binding. Thus, application of the borate-containing ionic cocktail represents a new topical lavage approach for removing apatite-bound heterocyclic N-BPs from exposed necrotic bone in bisphosphonate-related osteonecrosis of the jaw. STATEMENT OF SIGNIFICANCE: Long-term oral consumption and injections of nitrogen-containing bisphosphonates (N-BPs) may result in death of the jaw bone when there is traumatic injury to the bone tissues. To date, there is no effective treatment for such a condition. This work reported the use of an ionic cocktail derived from water-soluble borate glass microfibers to displace the most potent type of N BPs that are bound strongly to the mineral component on bone surfaces. The mechanism responsible for such an effect has been identified to be cation mediated complexation of borate anions with negatively-charged N-BPs, allowing them to be released from the mineral surface. This borate-containing cocktail may be developed into a novel topical rinse for removing mineral-bound N-BPs from exposed dead bone. PMID- 26675129 TI - Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments. AB - The experimental systems that recapitulate the complexity of native tissues and enable precise control over the microenvironment are becoming essential for the pre-clinical tests of therapeutics and tissue engineering. Here, we described a strategy to develop an in vitro platform to study the developmental biology of craniofacial osteogenesis. In this study, we directly osteo-differentiated cranial neural crest cells (CNCCs) in a 3-D in vitro bioengineered microenvironment. Cells were encapsulated in the gelatin-based photo crosslinkable hydrogel and cultured up to three weeks. We demonstrated that this platform allows efficient differentiation of p75 positive CNCCs to cells expressing osteogenic markers corresponding to the sequential developmental phases of intramembranous ossification. During the course of culture, we observed a decrease in the expression of early osteogenic marker Runx2, while the other mature osteoblast and osteocyte markers such as Osterix, Osteocalcin, Osteopontin and Bone sialoprotein increased. We analyzed the ossification of the secreted matrix with alkaline phosphatase and quantified the newly secreted hydroxyapatite. The Field Emission Scanning Electron Microscope (FESEM) images of the bioengineered hydrogel constructs revealed the native-like osteocytes, mature osteoblasts, and cranial bone tissue morphologies with canaliculus-like intercellular connections. This platform provides a broadly applicable model system to potentially study diseases involving primarily embryonic craniofacial bone disorders, where direct diagnosis and adequate animal disease models are limited. PMID- 26675130 TI - Modulation of MAPK signalling by immobilized adhesive peptides: Effect on stem cell response to BMP-9-derived peptides. AB - Biomimetic materials were developed to regulate stem cell behaviour. We have analyzed the influence of polycaprolactone (PCL) films, functionalized with adhesive peptides derived from fibronectin (pFibro) or bone sialoprotein (pBSP), on the response of murine multipotent C3H10T1/2 cells to bone morphogenetic protein-9 (BMP-9) and its derived peptides (pBMP-9 and SpBMP-9). PCL-pFibro promoted better cell cytoskeleton organization and faster focal adhesion kinase activation than did PCL-pBSP. PCL-pFibro also promoted MAPK signalling to improve the cell response to BMP-9 by inactivating ERK1/2 and stimulating p38 and JNK. BMP-9, pBMP-9 and SpBMP-9 induced greater phosphorylation of Smad1/5/8 in cells attached to PCL-pFibro than in cells on PCL-pBSP. These phosphorylated Smad1/5/8 were translocated to the nucleus. BMP-9 and its derived peptides restored the phosphorylation of JNK in cells on PCL-pBSP, but it remained less phosphorylated than in cells on PCL-pFibro stimulated with pBMP-9 and SpBMP-9. Cells attached to PCL-pFibro contained more Runx2, essential for stem cell commitment to become osteoblasts, than did cells on PCL-pBSP when incubated with BMP-9 and its derived peptides. Runx2 was no longer detected when the cells were pre-treated with JNK inhibitor. Therefore pFibro plus BMP-9 and its derived peptides may be a promising strategy to develop biomimetic materials. STATEMENT OF SIGNIFICANCE: Biomaterials functionalized with adhesive peptides to favour bone repair have generated a great interest over the past decade. However, the effect of these materials on the ability of cells to respond to growth factors remains poorly known. One major growth factor subfamily involved in bone formation is the bone morphogenetic protein (BMP). However, these BMPs are expensive. We therefore developed less costly derived molecules. We showed how adhesive peptides derived from bone matrix proteins grafted onto polymer films affect the intracellular signalling and thus the ability of stem cells to be activated by BMP and its derived molecules. We have therefore identified a combination of bioactive polymers and BMP molecules that direct the stem cells towards bone forming cells. PMID- 26675131 TI - L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice. AB - Microglia activation-induced neuroinflammation contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglia activation and reduction of major neurotoxic cytokines have been becoming a therapeutic strategy for neurodegenerative diseases. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and Alzheimer's disease animal models. The present study investigated the immune modulatory effects of L-NBP on pro inflammatory cytokines and microglia activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Our results showed that systemic LPS treatment induced microglia activation in the brain. L-NBP treatment significantly suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor (TNFalpha), interlukin-1beta (IL-1beta), interlukin 6 (IL-6), and interlukin-10 (IL-10) in LPS-treated mice. At the meantime, L-NBP treatment decreased the morphological activation of microglia. In addition, the phosphorylation level of JNK MAP kinase-signaling pathway was also inhibited by L NBP in LPS-treated mice. Furthermore, L-NBP upregulated the expression of heme oxygenase (HO)-1, a key element in the anti-inflammation and anti-oxidative stress. These results suggested that L-NBP might be a promising candidate in delaying and reversing the progress of neurodegenerative diseases by inhibiting microglia activation. PMID- 26675133 TI - Incorporating the effect of fractionation in the evaluation of proton plan robustness to setup errors. AB - To ensure the safe delivery of proton therapy treatments it is important to evaluate the effect of potential uncertainties, such as patient mispositioning, on the intended dose distribution. However, it can be expected that the uncertainty resulting from patient positioning is reduced in a fractionated treatment due to the convergence of random variables with the delivery of repeated treatments. This is neglected by current approaches to robustness analysis resulting in an overly conservative assessment of the robustness which can lead to sub-optimal plans. Here, a fast method of accounting for this reduced uncertainty is presented. An estimated bound to the error in the dose distribution resulting from setup uncertainty over a specified number of fractions is calculated by considering the distribution of values for each voxel across 14 initial error scenarios. The bound on the error in a given voxel is estimated using a 99.9% confidence limit assuming a convergence towards a normal distribution in line with the central limit theorem, and a correction of [Formula: see text] accounting for the reduction in the standard deviation over n fractions. The proposed method was validated in 5 patients by comparison to Monte Carlo simulations of 300 treatment courses. A voxelwise and volumetric analysis of the estimated and simulated bounds to the uncertainty in the dose distribution demonstrate that the proposed technique can be used to assess proton plan robustness more accurately allowing for less conservative treatment plans. PMID- 26675132 TI - The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. AB - Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Galphagust(-/-) mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model. PMID- 26675134 TI - Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications. AB - BACKGROUND: Fibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen. METHODS: A series of plasma samples was obtained from two individuals suffering an acute phase response. Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and beta1,4 galactosidase. RESULTS: The Bbeta and gamma chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bbeta chain showed an additional decrease corresponding to a further loss of NAcGlc. Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. beta1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal. CONCLUSIONS AND IMPLICATIONS: The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge. PMID- 26675135 TI - Guar gum succinate as a carrier for colon-specific drug delivery. AB - A novel type of pH-sensitive colon-specific controlled drug delivery carrier based on guar gum succinate (GGS) was prepared by reacting guar gum (GG) with succinic anhydride (SA) in the presence of 4-dimethylaminopyridine (DMAP). The formation of GGS was confirmed by FT-IR and (1)H NMR and characterized using XRD techniques. GGS microparticles with 460-740 MUm in size were prepared using sodium trimetaphosphate (STMP) as a cross-linking agent. The size and morphologies of GGS microparticles were assessed by scanning electron microscopy (SEM). The swelling degree of the GGS microparticles was found to be higher in pH 7.4 than in pH 1.2. In addition, GGS microparticles showed a pH dependent drug release profile when compared to the GG microparticles. The MTT assay revealed that there is no apparent cytotoxicity of GGS against a mouse mesenchymal stem cell line at a concentration range of 0-200 MUg/ml. These results confirm that GGS could be used as a carrier for colon-specific drug delivery. PMID- 26675136 TI - Macromolecular cross-linked enzyme aggregates (M-CLEAs) of alpha-amylase. AB - Macromolecular cross-linked enzyme aggregates (M-CLEAs) of alpha-amylase were prepared by precipitation and subsequent cross-linking. The non-toxic, biodegradable, biocompatible, renewable polysaccharide based macromolecular cross linkers viz. agar, chitosan, dextran, and gum arabic were used as a substitute for traditional glutaraldehyde to augment activity recovery toward macromolecular substrate. Macromolecular cross-linkers were prepared by periodate mediated controlled oxidation of polysaccharides. The effects of precipitating agent, concentration and different cross-linkers on activity recovery of alpha-amylase CLEAs were investigated. alpha-Amylase aggregated with ammonium sulphate and cross-linked by dextran showed 91% activity recovery, whereas glutaraldehyde CLEAs (G-CLEAs) exhibited 42% activity recovery. M-CLEAs exhibited higher thermal stability in correlation with alpha-amylase and G-CLEAs. Moreover, dextran and chitosan M-CLEAs showed same affinity for starch hydrolysis as of free alpha amylase. The changes in secondary structures revealed the enhancements in structural and conformational rigidity attributed by cross-linkers. Finally, after five consecutive cycles dextran M-CLEAs retained 1.25 times higher initial activity than G-CLEAs. PMID- 26675137 TI - Heterologous overexpression and biochemical characterization of the (galactophospho)lipase from Fusarium solani in Pichia pastoris that is expressed in planta. AB - High-level extracellular production of Fusarium solani (galactophospho)lipase, named FSL, was achieved using a Pichia pastoris X33 expression system. The (galactophospho) lipase encoding gene was cloned into pGAPZalphaA with the Saccharomyces cerevisiae alpha-factor signal sequence by two different ways. The two constructs consist of an additional sequence of a (His)6-tag of the vector fused to the N-terminus of this enzyme (tFSL) while the other expression vector was constructed without any additional sequence (rFSL). Compared to the native enzyme (nFSL) (18.75 mg/L), a high level secretion of rFSL (310 mg/L) and tFSL (240 mg/L) was achieved providing an important improvement in enzyme production. Biochemical characterization showed that pure recombinant proteins (rFSL and tFSL) presented similar behaviour towards triglycerides, phospholipid and galactolipid. Like the nFSL, rFSL and tFSL are active at high concentration of bile salts (4mM) and calcium ions enhanced lipase activity. During plant infection, transcripts of this fungal lipase gene were detected 3, 7 and 10 days post infection. PMID- 26675139 TI - Additive polarizabilities in ionic liquids. AB - An extended designed regression analysis of experimental data on density and refractive indices of several classes of ionic liquids yielded statistically averaged atomic volumes and polarizabilities of the constituting atoms. These values can be used to predict the molecular volume and polarizability of an unknown ionic liquid as well as its mass density and refractive index. Our approach does not need information on the molecular structure of the ionic liquid, but it turned out that the discrimination of the hybridization state of the carbons improved the overall result. Our results are not only compared to experimental data but also to quantum-chemical calculations. Furthermore, fractional charges of ionic liquid ions and their relation to polarizability are discussed. PMID- 26675140 TI - Cardiometabolic Health in African Immigrants to the United States: A Call to Re examine Research on African-descent populations. AB - In the 20th century, Africans in Sub-Saharan Africa had lower rates of cardiometabolic disease than Africans who migrated. However, in the 21st century, beyond infectious diseases, the triple epidemics of obesity, diabetes and hypertension have taken hold in Africa. Therefore, Africans are acquiring these chronic diseases at different rates and different intensity prior to migration. To ensure optimal care and health outcomes, the United States practice of grouping all African-descent populations into the "Black/African American" category without regard to country of origin masks socioeconomic and cultural differences and needs re-evaluation. Overall, research on African-descent populations would benefit from a shift from a racial to an ethnic perspective. To demonstrate the value of disaggregating data on African-descent populations, the epidemiologic transition, social, economic, and health characteristics of African immigrants are presented. PMID- 26675138 TI - Convergence of cMyc and beta-catenin on Tcf7l1 enables endoderm specification. AB - The molecular machinery that directs formation of definitive endoderm from pluripotent stem cells is not well understood. Wnt/beta-catenin and Nodal signalling have been implicated, but the requirements for lineage specification remain incompletely defined. Here, we demonstrate a potent effect of inhibiting glycogen synthase kinase 3 (GSK3) on definitive endoderm production. We find that downstream of GSK3 inhibition, elevated cMyc and beta-catenin act in parallel to reduce transcription and DNA binding, respectively, of the transcriptional repressor Tcf7l1. Tcf7l1 represses FoxA2, a pioneer factor for endoderm specification. Deletion of Tcf7l1 is sufficient to allow upregulation of FoxA2 in the presence of Activin. In wild-type cells, cMyc contributes by reducing Tcf7l1 mRNA, while beta-catenin acts on Tcf7l1 protein. GSK3 inhibition is further required for consolidation of endodermal fate via upregulation of Sox17, highlighting sequential roles for Wnt signalling. The identification of a cMyc/beta-catenin-Tcf7l1-FoxA2 axis reveals a de-repression mechanism underlying endoderm induction that may be recapitulated in other developmental and patho logical contexts. PMID- 26675141 TI - Effects of sub-Tenon's capsule triamcinolone acetonide injection combined with microaneurysm photocoagulation on diabetic macular edema. AB - PURPOSE: To compare the effects of sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME). PATIENTS AND METHODS: The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments. RESULTS: The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non SRD group than in the SRD+ group after STTA + MAPC. CONCLUSION: Our findings indicate that MAPC has an additive effect in the non-SRD type. PMID- 26675143 TI - Derivation of epithelial-like cells from eyelid fat-derived stem cells in thermosensitive hydrogel. AB - Injectable hydrogel is one of the great interests for tissue engineering and cell encapsulation. In the study, the thermosensitive chitosan/gelatin/beta-glycerol phosphate (C/G/GP) disodium salt hydrogels were designed and investigated by different analyses. The eye fat-derived stem cells were used to evaluate the biocompatibility of hydrogels based on their phenotypic profile, viability, proliferation, and attachment ability. The results show that the sol/gel transition temperature of the C/G/GP hydrogel was in the range of 31.1-33.8 degrees C at neutral pH value, the gelation time was shortened, and the gel strength also improved at body temperature when compared with the C/GP hydrogel. In vitro cell culture experiments with eyelid fat-derived stem cells in hydrogel showed beneficial effects on the cell phenotypic morphology, proliferation, and differentiation. Microscopic figures showed that the eyelid fat stem cell were firmly anchored to the substrates and were able to retain a normal stem cell phenotype. Immunocytochemistry (ICC) and real-time-PCR results revealed change in the expression profile of eyelid fat stem cells grown with hydrogels when compared to those grown on control in epithelial induction condition. This study indicates that using chitosan/gelatin/beta-glycerol phosphate hydrogel for cell culture is feasible and may apply in minimal invasive surgery in the future. PMID- 26675142 TI - Cumulative social risk exposure and risk of cancer mortality in adulthood. AB - BACKGROUND: Adults in the United States (U.S) can be simultaneously exposed to more than one social risk factor over their lifetime. However, cancer epidemiology tends to focus on single social risk factors at a time. We examined the prospective association between cumulative social risk exposure and deaths from cancer in a nationally representative sample of U.S. adults. METHODS: The study included 8745 adults (aged>=40 years) in the NHANES Survey III Mortality Study over a median follow-up of 13.5 years (1988-1994 enrollment dates and 1988 through 2006 for mortality data). Social risk factors (low family income, low education level, minority race, and single-living status) were summed to create a cumulative social risk score (0 to >=3). We used Cox proportional hazard models to estimate age- and sex-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association between cumulative social risk with deaths from all-cancers combined, tobacco-related cancers, and screening-detectable cancers. RESULTS: Deaths from all-cancers combined (P for trend=0.001), tobacco related cancers (P for trend=<0.001), and lung cancer (P for trend=0.01) increased with an increasing number of social risk factors. As compared with adults with no social risk factors, those exposed to >=3 social risk factors were at increased risk of deaths from all-cancers combined (HR=1.8, 95% CI=1.3-2.4), tobacco-related cancers (HR=2.6, 95% CI: 1.6-4.0), and lung cancer (HR=2.3, 95% CI=1.3-4.1). CONCLUSIONS: U.S. adults confronted by higher amounts of cumulative social risk appear to have increased mortality from all-cancers combined, tobacco related cancers, and lung cancer. An enhanced understanding of the cumulative effect of social risk factors may be important for targeting interventions to address social disparities in cancer mortality. PMID- 26675144 TI - THE APPLICATION OF IMPROVED, STRUCTURED AND INTERACTIVE GROUP LEARNING METHODS IN DIAGNOSTIC RADIOLOGY. AB - This study provides an example on how it is possible to design environments in a diagnostic radiology department that could meet learning demands implied by the introduction of new imaging technologies. The innovative aspect of the design does not result from the implementation of any specific tool for learning. Instead, advancement is achieved by a novel set-up of existing technologies and an interactive format that allows for focussed discussions between learners with different levels of expertise. Consequently, the study points to what is seen as the underexplored possibilities of tailoring basic and specialist training that meet the new demands given by leading-edge technologies. PMID- 26675145 TI - EFFECTIVE DOSE TO PATIENTS FROM THORACIC SPINE EXAMINATIONS WITH TOMOSYNTHESIS. AB - The purposes of the present work were to calculate the average effective dose to patients from lateral tomosynthesis examinations of the thoracic spine, compare the results with the corresponding conventional examination and to determine a conversion factor between dose-area product (DAP) and effective dose for the tomosynthesis examination. Thoracic spine examinations from 17 patients were included in the study. The registered DAP and information about the field size for each projection radiograph were, together with patient height and mass, used to calculate the effective dose for each projection radiograph. The total effective doses for the tomosynthesis examinations were obtained by adding the effective doses from the 60 projection radiographs included in the examination. The mean effective dose was 0.47 mSv (range 0.24-0.81 mSv) for the tomosynthesis examinations and 0.20 mSv (range 0.07-0.29 mSv) for the corresponding conventional examinations (anteroposterior + left lateral projection). For the tomosynthesis examinations, a conversion factor between total DAP and effective dose of 0.092 mSv Gycm(-2) was obtained. PMID- 26675146 TI - Hybrid Approach to Management of Complex Aortic Arch Pathologies: A Single-Center Experience in China. AB - BACKGROUND: The purpose of this study is to summarize a single-center experience and midterm outcomes of a combined supra-aortic debranching and thoracic endovascular aortic repair (TEVAR) for hybrid operation on patients with complex aortic arch disease. METHODS: From 2012 to 2015, 43 consecutive patients (37 male and 6 females) who underwent a hybrid operation for complex aortic arch disease were retrospectively analyzed. Of the 43 patients, 12 were diagnosed with type A aortic dissection (AD), 27 with complicated type B AD involving the aortic arch, 2 with aortic arch aneurysm, and 2 with type A penetrating atherosclerosis ulcer. RESULTS: The patients' mean age was 52.3 +/- 11.3 years. Hybrid operation was technically successful in all patients. The overall 30-day mortality and in hospital mortality rates were 2.3% (1 of 43), with 1 patient dying at days 18 of severe aspiration pneumonia after procedure. Thirty-day paraplegia and stroke were 0%. Complication included 1 newly onset renal insufficiency and type II endoleak. After a median follow-up of 15 months (range, 6-26 months), the overall mortality was 7.1% (3 of 42), with Kaplan-Meier survival estimate of 91% at 1 year. Only one late death was considered aorta-related. computed tomography (CT) scanning was performed at 6 months and annually thereafter, and 2 patients were observed with type Ib endoleak and type II endoleak, respectively. For the patient with type Ib endoleak, distal extension was performed successfully. No late extra-anatomic bypass occlusion and stent-graft migration were found on CT scans or ultrasound. CONCLUSIONS: These initial results suggest that hybrid operation with supra-aortic debranching, and TEVAR is an acceptable treatment option for patients with complex aortic arch disease. Short-term and midterm outcomes are acceptable. Further research with large sample size and long-term follow-up is needed. PMID- 26675147 TI - Inadequate collaboration: A challenge to reaching global targets for non communicable disease control and prevention. PMID- 26675148 TI - World military expenditures and global cardiovascular mortality. AB - Can we estimate the consequences of world military expenditures for the physical and mental health of nations that produce and purchase armaments? If anxiety and fear are promoting military expenditures, then those sentiments may well reflect poorer mental health and war-related stress as it influences cardiovascular illness rates. Further, extensive military expenditure by a society implies that other societal needs are allocated fewer resources, including nutrition, water and sanitation, health care, and economic development. We use a model focused on military expenditures to predict cardiovascular mortality in world samples of industrialized and developing countries over 2000-2011. The cardiovascular mortality model controls for economic development, smoking, body mass index, systolic blood pressure, and carbon dioxide emissions. Military expenditures as proportion of gross domestic product show significant positive relations to cardiovascular disease mortality in linear multiple regression analyses, using both cross-sectional and pooled cross-sectional time-series approaches. PMID- 26675149 TI - On the Varieties of Empathic-Trance Experiences. PMID- 26675150 TI - Claire Frederick, M.D., 1932-2015. PMID- 26675151 TI - Hypnosis and Empathy: A Complex Relationship. AB - This article takes its inspiration from Wickramasekera II's empathic involvement theory of hypnosis. That model illuminates the mutual territory of hypnosis and empathy-common to much interaction between hypnotist and subject, and to the internal process of subjects as they enact suggestions of the hypnotist. However, the present article suggests that the overlap is not as ubiquitous as the empathic involvement theory asserts. Other aspects of hypnosis involve disengagement from real persons in the environment and dissociating from other ego states of the self. Amnesia and certain uses of focused attention in the hypnotic context run counter to empathy. The fantasizer type of high hypnotizables experiences hypnosis more empathically than do the equally hypnotizable dissociater type. This article also explores the relationship of hypnosis and empathy to other related states, including meditation, dreaming, and psychedelic drugs. The conclusion is that empathy is an important component of many hypnotic phenomena, but that the relationship is as partial and complex as the manner in which other traits, such as imagery ability and dissociation, map onto hypnosis. PMID- 26675152 TI - Empathy Examined From Perspectives of Neuroscience and Artistic Imagination. AB - This response to Ian E. Wickramasekera II's article, Mysteries of Hypnosis and the Self Are Revealed by the Psychology and Neuroscience of Empathy, is addressed from a joint perspective on consciousness comprising two related orientations: neuroscience and artistic imagination. We find that the central importance of empathy to empathic involvement theory (Wickramasekera II, 2015) reflects the pivotal nature of empathy in the brain and in the relational exchange implicit in the psychotherapeutic process, particularly when using art in therapy. We offer a preliminary unpacking of the roles related to key psychological processes, such as imagination, that are implicated in clinical uses of verbal and visual empathic resonance. PMID- 26675153 TI - An Intersubjective View of Empathy and Hypnotic Trance: Response to Wickramasekera II. AB - In response to Wickramasekera II's description of his empathic involvement theory of hypnosis in "Mysteries of hypnosis and the self are revealed by the psychology and neuroscience of empathy" (Wickramasekera II, 2015), Henning offers further reflections on what empathy might be and what it allows therapists to do, particularly in conditions of hypnotic trance. She defines her intersubjective view of hypnotic trance as an experience in which client and therapist mutually engage in a shared state of consciousness, and a mutual bidirectional or multidirectional exchange of verbal and nonverbal, as well as conscious and unconscious, material occurs, and which may include shared taking on of roles and expectations in each party, as suggested by the other, particularly when both client and therapist are highly hypnotizable. Research on the concept of "mutual hypnosis," or co-trance, is reviewed, and barriers to scholarly discussions about intersubjectivity in therapy relationships are described. Concepts from other disciplines and traditions, including quantum physics, transpersonal psychology, contemplative Christianity, and shamanistic practices and trance in other cultures are then offered to clarify the processes of intersubjectivity, and perspectives about empathy and hypnotic co-trance are offered from the context of the author's own clinical work as a trauma therapist. Finally, suggestions are provided for future research approaches and methods to further explore and understand these phenomena. PMID- 26675154 TI - The "Mysteries of Hypnosis:" Helping Us Better Understand Hypnosis and Empathic Involvement Theory (EIT). AB - Wickramasekera II (2015) has penned a comprehensive and thoughtful review article demonstrating how empathy is intimately involved in the psychology and neurophysiology of hypnosis and the self. Hypnosis is a very "mental" or subjective phenomenon for both the client and the research participant. To better assess the mind of the client/participant during hypnosis, it is my belief that we need to generate more "precise" phenomenological descriptors of the mind during hypnosis and related empathic conditions, as Wickramasekera II (2015) has suggested in his article. Although any phenomenological methodology will have its limits and disadvantages, noetics (as defined in the article below) can help us better understand hypnosis, empathic involvement theory, and the brain/mind/behavior interface. By quantifying the mind in a comprehensive manner, just as the brain is comprehensively quantified via fMRI and qEEG technologies, noetic analysis can help us more precisely assess the mind and relate it to the brain and human behavior and experience. PMID- 26675155 TI - Empathic Features and Absorption in Fantasy Role-Playing. AB - This study examined the levels of empathy and absorption of individuals who regularly play fantasy and science fiction role-playing games. A hypothesis was developed that higher levels of empathy would be found in individuals who fantasy role-play based upon previous research in hypnosis such as J. R. Hilgard's (1970) imaginative involvement hypothesis, research into the "fantasy prone" personality type (Wilson & Barber, 1981), and the empathic involvement hypothesis (Wickramasekera II & Szlyk, 2003). The participants in the current study were 127 fantasy role-players who volunteered and completed the Davis Interpersonal Reactivity Index (empathy) and the Tellegen Absorption Scale (absorption). The results demonstrated that those who play fantasy role-playing games scored significantly higher than the comparison group on the IRI scale of empathy, confirming the hypothesis that fantasy role-players report experiencing higher levels of empathic involvement with others. Correlational analysis between the measures demonstrated a significant positive correlation between empathy and absorption (r = .43, p < .001). These results collectively suggest that fantasy role-players have a uniquely empathically-imaginative style. The results also confirm and extend previous findings on the relationship between empathy and absorption as predicted by the Empathic Involvement Hypothesis (Wickramasekera II & Szlyk, 2003). PMID- 26675156 TI - Raising Relational Critical Consciousness to Enhance Empathy in Clinical Hypnosis. AB - Empathic involvement theory suggests that a trance-like experience occurs when a cross-relational empathic connection is achieved. The empathically-laden relational phenomenon is thought to enhance hypnosis. Empathic involvement theory suggests hypnotizables are highly empathic. By the same token, the relational empathic connection necessitates a highly empathic practitioner of hypnosis. In the United States, where values of individualism are thought to be socially embedded and internalized, practitioners of hypnosis and clients alike may be impeded by an individually oriented worldview to empathically connect with others. Raising a relational critical consciousness is promoted as a way to increase sensitivity to the marginalization of relationships, limit empathic effort burn-out, and promote cross-relational empathic connection. PMID- 26675157 TI - Expanding Empathy in Our Clinical Work: A Response to Wickramasekera II's (2015) "Mysteries of Hypnosis and the Self Are Revealed by the Psychology and Neuroscience of Empathy.". AB - Empathy is a central tenet of psychotherapeutic process. This article builds upon Wickramasekera II's (2015) "Mysteries of Hypnosis and the Self are Revealed by the Psychology and Neuroscience of Empathy," with particular focus on "empathetic involvement theory." A brief transtheoretical and research review of empathy is provided. A couple's therapy case illustration is provided to elucidate how one can expand "empathetic involvement theory" into clinical practice. Emphasis is placed upon the dimensions of sensation and body/mind connectedness. PMID- 26675158 TI - Hypnosis Without Empathy? Perspectives From Autistic Spectrum Disorder and Stage Hypnosis. AB - Despite volumes of published studies supporting the efficacy of hypnosis for ego strengthening, performance, and physical and psychological disorders, the precise nature of hypnosis, and in particular, the neurobiological underpinnings of trance-phenomenon, remains tenuous at best. With his empathic involvement theory of hypnosis, Wickramasekera II (2015) brings us closer to an understanding of the elusive nature of hypnotic processes by proposing a bridging of two long-standing and seemingly incongruent theories of hypnosis (i.e., neodissociative versus socio-cognitive). Borrowing from neuroscientific studies of empathy, the empathic involvement theory maintains that empathy, beyond any other human dynamic (including emotions, behavior, personality, and imagination), facilitates and enhances hypnotic experiences for both recipient and provider alike. By the same token, one can reasonably infer from the empathic involvement theory that non empathic individuals are less likely to benefit from hypnosis. With this perspective in mind, the empathic involvement theory's identification of empathy as an apparent "Holy Grail" of the neural underpinnings and precise nature of hypnosis may be challenged on a number of grounds. Individuals with autistic spectrum disorder, especially those suffering from alexithymia, have been identified as empathy deficient, and therefore according to the empathic involvement theory would be classified as "low-hypnotizable," yet empirical studies, albeit limited in number, suggest otherwise. Furthermore, hypnotic inductions of audience volunteers by stage hypnotists challenge the empathic involvement theory's supposition that empathy is a required component of hypnosis. It is this author's contention that empathy is a beneficial, though not essential, element of successful hypnosis. PMID- 26675159 TI - Anxious in love, by Carolyn Daitch and Lissah Lorberbaum. PMID- 26675160 TI - Relief from hot flashes. The natural, drug-free program to reduce hot flashes, improve sleep, and ease stress, by Gary Elkins. PMID- 26675161 TI - Review of the International Literature. PMID- 26675162 TI - Spinal Tuberculosis Resembling Neoplastic Lesions on MRI. AB - BACKGROUND: Tuberculous spondylitis is one of the commonest forms of skeletal tuberculosis in developing countries like India causing significant morbidity due to compression of spinal cord and adjacent nerve roots. Diagnosis and intervention at early stage can prevent permanent damage such as spinal deformity and neurological deficits. AIM: The purpose of this study was to demonstrate atypical MRI features in cases of tubercular spondylitis resembling neoplastic lesions and to stress that tuberculous spondylitis should be one of the differential diagnoses in any spinal pathology especially in developing countries. MATERIALS AND METHODS: This was a prospective study done in the patients diagnosed as tuberculous spondylitis on 0.2 T Siemens MRI between June 2011 and December 2014 in a tertiary care hospital in India. Total 529 cases of tubercular spinal lesions were diagnosed. Out of which only 59 patients showed atypical features on MR imaging which resembled neoplastic lesions were included in the study. The diagnosis was confirmed by cytology, histopathology, serology and corroborative findings. RESULTS: Lumbo-sacral region involvement (30.5%) is the commonest in our study followed by dorsal and cervical region. Multiple level lesions are seen in 14 cases (23.7%). All the 59 (100%) cases show no involvement of intervetebral disc. Posterior appendage involvement seen in 32 cases (54.2%). Soft tissue component seen in Intraspinal (37.2%) and paraspinal (45.7%) compartments. Cord compression seen in 19 cases (32.2%), out which only 7 cases (11.8%) shows cord oedema. CONCLUSION: On MRI, tubercular spondylitis may have variable pictures on imaging. For any spinal and paraspinal lesions, we should also consider the possibility of tubercular aetiology along with other. Since early diagnosis avoids unnecessary delay in the treatment thereby reducing morbidity and possible complications. PMID- 26675163 TI - Pancreatic Cancer: Clinical Significance of Biomarkers. AB - BACKGROUND: Improvement in the prognosis of patients with pancreatic cancer, novel effective screening and diagnostic strategies and treatments are needed. Recent advances in the understanding of pancreatic carcinogenesis and tumor microenvironment have allowed identification of biomarkers for screening, diagnosis and prediction of cancer treatments, including novel therapies targeting specific cancer or stromal cell subpopulations. Personalized therapy in pancreatic cancer is also promising as several drugs such as S1, capecitabine and gemcitabine reportedly have significant therapeutic effects. Predictive markers are thus needed to select patients most likely to benefit from therapies based on gemcitabine or other drugs. SUMMARY: We review the clinical significance of promising screening, diagnostic, predictive and prognostic biomarkers based on genetic and epigenetic alterations and microRNA abnormalities in pancreatic cancer. We also review new types of biomarkers based on stromal cells, such as pancreatic stellate cells, in the microenvironment of pancreatic cancer. PMID- 26675164 TI - Co-evolution of Bacterial Ribosomal Protein S15 with Diverse mRNA Regulatory Structures. AB - RNA-protein interactions are critical in many biological processes, yet how such interactions affect the evolution of both partners is still unknown. RNA and protein structures are impacted very differently by mechanisms of genomic change. While most protein families are identifiable at the nucleotide level across large phylogenetic distances, RNA families display far less nucleotide similarity and are often only shared by closely related bacterial species. Ribosomal protein S15 has two RNA binding functions. First, it is a ribosomal protein responsible for organizing the rRNA during ribosome assembly. Second, in many bacterial species S15 also interacts with a structured portion of its own transcript to negatively regulate gene expression. While the first interaction is conserved in most bacteria, the second is not. Four distinct mRNA structures interact with S15 to enable regulation, each of which appears to be independently derived in different groups of bacteria. With the goal of understanding how protein-binding specificity may influence the evolution of such RNA regulatory structures, we examine whether examples of these mRNA structures are able to interact with, and regulate in response to, S15 homologs from organisms containing distinct mRNA structures. We find that despite their shared RNA binding function in the rRNA, S15 homologs have distinct RNA recognition profiles. We present a model to explain the specificity patterns observed, and support this model by with further mutagenesis. After analyzing the patterns of conservation for the S15 protein coding sequences, we also identified amino acid changes that alter the binding specificity of an S15 homolog. In this work we demonstrate that homologous RNA binding proteins have different specificity profiles, and minor changes to amino acid sequences, or to RNA structural motifs, can have large impacts on RNA protein recognition. PMID- 26675165 TI - [Bronchial stump aspergillosis. An unusual disease]. PMID- 26675166 TI - Changes in Prices After an Excise Tax to Sweetened Sugar Beverages Was Implemented in Mexico: Evidence from Urban Areas. AB - In 2014 an excise tax to non-alcoholic sweetened beverages (SSB) was implemented in Mexico. The objective of this paper is to study whether and to what degree these taxes passed-through onto SSB prices in urban areas overall and by region, type of beverage and package size. Prices were obtained from the National Institute of Statistics and Geography from 2011 to 2014. We applied a pre-post quasi-experimental approach using fixed effects models. In sensitivity analysis we applied other model specifications to test the robustness of the findings and we also present weighted estimations based on household purchases. The dependent variables are real prices of a specific beverage category; the main independent variables are dummies for each month of 2014, and the models adjust for time trends and seasonality. Results suggest that the SSB tax passed along to consumers for all SSBs and we found overshifting for the carbonated SSBs. A greater effect is seen among the small package sizes, and we see heterogeneous effects by region. Estimating the effect of the tax on prices is important to understand the potential effect on consumption. PMID- 26675167 TI - Circulating microRNA 132-3p and 324-3p Profiles in Patients after Acute Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI. METHODS: Peripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses. RESULTS: We demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324]. CONCLUSION: Our study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non DCI groups were not statistically significant. PMID- 26675168 TI - Studies on the Glutathione-Dependent Formaldehyde-Activating Enzyme from Paracoccus denitrificans. AB - Formaldehyde is a toxin and carcinogen that is both an environmental pollutant and an endogenous metabolite. Formaldehyde metabolism, which is probably essential for all aerobic cells, likely proceeds via multiple mechanisms, including via a glutathione-dependent pathway that is widely conserved in bacteria, plants and animals. However, it is unclear whether the first step in the glutathione-dependent pathway (i.e. formation of S-hydroxymethylglutathione (HMG)) is enzyme-catalysed. We report studies on glutathione-dependent formaldehyde-activating enzyme (GFA) from Paracoccus denitrificans, which has been proposed to catalyse HMG formation from glutathione and formaldehyde on the basis of studies using NMR exchange spectroscopy (EXSY). Although we were able to replicate the EXSY results, time course experiments unexpectedly imply that GFA does not catalyse HMG formation under standard conditions. However, GFA was observed to bind glutathione using NMR and mass spectrometry. Overall, the results reveal that GFA binds glutathione but does not directly catalyse HMG formation under standard conditions. Thus, it is possible that GFA acts as a glutathione carrier that acts to co-localise glutathione and formaldehyde in a cellular context. PMID- 26675170 TI - Bifid rib - usefulness of chest ultrasound. A case report. AB - The paper presents the possibility of using ultrasonography in the diagnosis of a congenital rib anomaly in the form of bifid rib. Bifid rib is a rare congenital abnormality of anterior chest wall. It manifests as a chest "lump." Such lesions are detected during a routine physical examination or chest X-ray which is often performed for other reasons. The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%) and it accounts for approximately 20% of all congenital rib anomalies. It is usually an unilateral lesion. The cases presented herein constitute the first pediatric cases in the available literature in which bifid rib anomaly was visualized by ultrasound examination. PMID- 26675169 TI - Differential Molecular Stress Responses to Low Compared to High Doses of Ionizing Radiation in Normal Human Fibroblasts. AB - Understanding the mechanisms producing low dose ionizing radiation specific biological effects represents one of the major challenges of radiation biology. Although experimental evidence does suggest that various molecular stress response pathways may be involved in the production of low dose effects, much of the detail of those mechanisms remains elusive. We hypothesized that the regulation of various stress response pathways upon irradiation may differ from one another in complex dose-response manners, causing the specific and subtle low dose radiation effects. In the present study, the transcription level of 22 genes involved in stress responses were analyzed using RT-qPCR in normal human fibroblasts exposed to a range of gamma-doses from 1 to 200 cGy. Using the alkali comet assay, we also measured the level of DNA damages in dose-response and time course experiments. We found non-linear dose responses for the repair of DNA damage after exposure to gamma-radiation. Alterations in gene expression were also not linear with dose for several of the genes examined and did not follow a single pattern. Rather, several patterns could be seen. Our results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for different genes. PMID- 26675172 TI - Surgical and Locoregional Therapy of HCC: TACE. AB - Transcatheter arterial chemoembolization (TACE) is performed worldwide for patients with intermediate-stage hepatocellular carcinoma (HCC). TACE has produced survival advantages in two randomized controlled trials and a meta analysis, and is currently the mainstay of treatment for this stage of HCC. However, there are currently no global guidelines regarding the dose, choice or combination of cytotoxic agents for TACE; therefore, it is difficult to compare data from different TACE studies. In Japan, most of the TACE procedures have been based on iodized oil as conventional TACE, utilizing the microembolic and drug carrying characteristic of iodized oil. Superselective TACE with lipiodol is the primary TACE procedure that has reported satisfactory levels of local control associated with a lower risk of complications. Conversely, TACE performed using drug-eluting beads has been widely used in western countries, and this has shown similar tumor response and median survival compared to conventional TACE. Moreover, the combination of TACE and molecular targeted agents is now ongoing to evaluate the synergistic effect. In this review, the indication, technical issues, and complications of TACE are reviewed. PMID- 26675171 TI - A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma. AB - BACKGROUND: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC. METHODS: Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations. RESULTS: Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06 6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein. CONCLUSIONS: Our study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention. PMID- 26675173 TI - Lampropedia cohaerens sp. nov., a biofilm-forming bacterium isolated from microbial mats of a hot water spring, and emended description of the genus Lampropedia. AB - A biofilm-forming, Gram-stain-negative, aerobic, catalase-positive but oxidase negative strain, designated CT6T, was isolated from the microbial mats (~45 degrees C) of a hot water spring, located within the Himalayan ranges at Manikaran, Himachal Pradesh, India. Strain CT6T formed white, smooth colonies with irregular margins. Transmission electron microscopy revealed coccoid, non flagellated cells with wavy boundaries. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain CT6T belongs to the genus Lampropedia with a sequence similarity value of 95.4 % to the sole member of this genus, Lampropedia hyalina ATCC 11041T. Strain CT6T was found to have phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. The major cellular fatty acids were C16 : 0, summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c), C14 : 0, C19 : 0omega8c cyclo and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c). The major respiratory quinone was ubiquinone-8. The major polyamines were putrescine, spermidine and the betaproteobacterial-specific 2-hydroxyputrescine. The DNA G+C content was 63.5 mol%. Based on the genotypic, phenotypic, physiological and biochemical data, strain CT6T is considered to represent a novel species of the genus Lampropedia, for which the name Lampropedia cohaerens sp. nov. is proposed ( = DSM 100029T = KCTC 42939T = MCC 2711T). PMID- 26675174 TI - Flexible sensors for biomedical technology. AB - Flexible sensing devices have gained a great deal of attention among the scientific community in recent years. The application of flexible sensors spans over several fields, including medicine, industrial automation, robotics, security, and human-machine interfacing. In particular, non-invasive health monitoring devices are expected to play a key role in the improvement of patient life and in reducing costs associated with clinical and biomedical diagnostic procedures. Here, we focus on recent advances achieved in flexible devices applied on the human skin for biomedical and healthcare purposes. PMID- 26675175 TI - Reach and effectiveness of an integrated community-based intervention on physical activity and healthy eating of older adults in a socioeconomically disadvantaged community. AB - The aim of this study is to assess the reach and effectiveness of an integrated community-based intervention designed to promote physical activity and healthy eating among older adults in a socioeconomically disadvantaged community in the Netherlands. The intervention was evaluated with a controlled pre-post quasi experimental design, with 430 randomly selected older adults participating in the intervention group and 213 in a control group at baseline. The intervention included a local media campaign and environmental approaches (e.g., community involvement) and was implemented during a 3-month high-intensity period, followed by a 6-month low-intensity one. Levels of physical activity and fruit and vegetable consumption were assessed at baseline and at 3 and 9 months after baseline. At the follow-up measurements, the intervention had reached respectively 68 and 69% of the participants in the intervention group. No significant differences were found between the intervention group and the control group in changes to any outcome except for transport-related PA at 3 and 9 months follow-up. The systematically developed community-based intervention reached a relatively large proportion of the participants, but had only small effects on the levels of physical activity and healthy eating in older adults in the short and medium term. PMID- 26675177 TI - [Guideline for twin pregnancies (Part 1): antenatal care and management for uncomplicated twins]. PMID- 26675176 TI - A randomized crossover study of web-based media literacy to prevent smoking. AB - Feasibly implemented Web-based smoking media literacy (SML) programs have been associated with improving SML skills among adolescents. However, prior evaluations have generally had weak experimental designs. We aimed to examine program efficacy using a more rigorous crossover design. Seventy-two ninth grade students completed a Web-based SML program based on health behavior theory and implemented using a two-group two-period crossover design. Students were randomly assigned by classroom to receive media literacy or control interventions in different sequences. They were assessed three times, at baseline (T0), an initial follow-up after the first intervention (T1) and a second follow-up after the second intervention (T2). Crossover analysis using analysis of variance demonstrated significant intervention coefficients, indicating that the SML condition was superior to control for the primary outcome of total SML (F = 11.99; P < 0.001) and for seven of the nine individual SML items. Results were consistent in sensitivity analyses conducted using non-parametric methods. There were changes in some exploratory theory-based outcomes including attitudes and normative beliefs but not others. In conclusion, while strength of the design of this study supports and extends prior findings around effectiveness of SML programs, influences on theory-based mediators of smoking should be further explored. PMID- 26675178 TI - [Noninvasive prenatal screen of trisomy-21 using maternal plasma fetal free RNA allelic ratio]. AB - OBJECTIVE: Through the detections of the heterozygote frequencies tests of fetal specific genes PLAC4 and COL6A2 mRNA alleles in plasma of pregnant women, to explore its possibility of application in the noninvasive prenatal screenings of trisomy-21. METHODS: A toltal of 500 cases (males and females 250 cases respectively)of Han ethnic groups with Henan Provice of China who were subject to the physical checkup clinic of the Third Affiliated Hospital, Zhengzhou University from June to December, 2013 were selected as the healthy physical checkup group, and such techniques as DNA sequencing and PCR-restriction fragment length polymorphism (RFLP) were adopted to the determinations of the heterozygote frequencies of the single nucleotide polymorphism (SNP) of the PLAC4 and COL6A2 genes in the maternal peripheral blood in the healthy physical checkup group, and the differential comparisons of the determination results of the SNP heterozygote frequencies and the corresponding heterozygote frequencies in the National Center for Biotechnology Information (NCBI) database; 30 cases of healthy pregnant women who spontaneously underwent pregnancy checkups at the maternity clinic were randomly selected as the healthy pregnancy group, and real-time fluorescence quantitative reverse transcription-PCR technique was adopted for determining the expression levels of PLAC4 and COL6A2 mRNA in the peripheral blood of pregnant women of 8 weeks, 10 weeks, 12 weeks, 14 weeks and 16 weeks; 40 cases of the same phase were selected for acting as the specimens for the karyotype analyses of the amniotic fluid cells, among which 20 cases were trisomy-21, and the 20 cases of the negative control group, and reverse transcription-multiplex ligation dependent probe amplification (RT-MLPA) technique was adopted for screening the fetal trisomy-21. RESULTS: (1) The allele heterozygote frequencies of the SNP of the healthy physical checkup group: determinations of the genotypes and hybrid rates of the 10 SNP sites of the PLAC4 and COL6A2 genes indicated that those with higher heterozygote frequencies were respectively rs7717, rs559, rs1044598, rs59066201 and rs1042917, with population coverage of 98%. Among them, the allele hybrid rates of rs59066201 were never seen in the NCBI database; in the respective comparisons of the allele hybrid rates of rs8130833, rs9977003 and rs7844 with the hybrid rates of the NCBI database, the variations had statistical significance (P < 0.05). (2) The expression levels of PLAC4 and COL6A2 mRNA of the different pregnancy weeks of the healthy pregnancy group: the levels of PLAC4 mRNA in the peripheral blood of women of 8 weeks, 10 weeks, 12 weeks, 14 weeks and 16 weeks of pregnancy were respectively 7.22 +/- 1.05, 8.02 +/- 1.41, 9.51 +/ 1.69, 11.33 +/- 2.11 and 13.31 +/- 2.58, with their expression levels rising along with the increase of the pregnancy weeks; among them, the comparison of pregnancy 8 weeks and pregnancy 10 weeks, the variations had no statistical significance (P > 0.05); in the mutual comparisons among the expression levels of the various pregnancy weeks, the variations had statistical significance (P < 0.05). The expression levels of COL6A2 mRNA in 8 weeks, 10 weeks, 12 weeks, 14 weeks and 16 weeks were respectively 8.95 +/- 1.28, 11.19 +/- 1.36, 15.00 +/- 1.58, 16.87 +/- 1.72 and 18.96 +/- 2.79, with their expression levels rising along with the increase of the pregnancy weeks, and in the mutual comparisons between the expression levels of the various pregnancy weeks, the variations all had statistical significance (P < 0.05). (3) Prenatal screenings of trisomy-21 in the validation group of the trisome: a total of 5 sites of rs7717, rs559, rs1044598, rs59066201 and rs1042917 were selected from the allele heterozygote frequencies of SNP sites were selected from the subjects of the healthy physical checkup group, and 10 cases of trisomy-21 specimens and 10 cases of negative CTR specimens were accurately determined, with the sensitivity reached 80% (17/20), and the specificity reached 90% (18/20). One case of the trisomy-21 and two negative cases were both homozygotes, and among the trisomy-21 specimens of two cases, only one SNP was a heterozygote, and it was impossible to conduct screenings on these 5 cases, with the screening accuracy reaching 100% (35/35). CONCLUSIONS: Fetal specific genes PLAC4 and COL6A2 mRNA are expressed in the peripheral blood of pregnant women in different gestational age; its expression level increases with the increase of gestational age. Among them, five SNP including rs7717, rs559, rs1044598, rs59066201 and rs1042917 show highest heterogeneity rate, which is different from the corresponding heterogeneity rate in NCBI database. RT-MLPA technology is a rapid, effective, noninvasive and low cost method of prenatal screening 21 trisomy. PMID- 26675179 TI - [Clinical analysis on selective uterine artery embolization combined with hysteroscopic surgery for exogenous cesarean scar pregnancy in 67 cases]. AB - OBJECTIVE: To investigate the safety and feasibility of uterine arterial embolization (UAE) combined with hystersocpic excisionl of exogenous cesarean scar pregnancy (CSP). METHODS: Totally 67 patients with exogenous CSP treated with selective UAE combined with hysterscopic surgery in Shengjing Hospital of China Medical University were analyzed retrospectively; 35 patients in Group A (thickness of the cesarean scar > 3 mm), while 32 patients in Group B (thickness of the cesarean scar <= 3 mm). The following clinical parameters including operative time, intraoperative blood loss, quantity of postoperative uterine drainage, postoperative hospital days, the time for the mass absorption and the return of beta-hCG to normal were compared. RESULTS: All hysterscopic procedures were successfully completed in Group A, and only one case underwent a second hysteroscopic excision due to the 1-month postoperative ultrasound examination indicating a mass located in the cesarean scar and a slow decline of beta-hCG. Three cases of Group B were transformed to laparoscopic or laparotomy operation and 7 cases underwent a second surgery. The volume of introperative blood loss was (97 +/- 41) ml in Group A and (161 +/- 92) ml in Group B, the difference was statistically significant (P < 0.01). But the operative time, quantity of postoperative uterine drainage, postoperative hospital days, the time for the retrun of beta-hCG to normal and the mass absorption in Group A were (36 +/- 9) minutes, (38 +/- 13) ml, (3.5 +/- 0.5) days, (26 +/- 5) days, (82 +/- 17) days, in Group B were (37 +/- 9) minutes, (42 +/- 16) ml, (4.0 +/- 0.7) days, (28 +/- 8) days, (88 +/- 15) days, respectively, the differences were not statistically significant (all P > 0.05). CONCLUSIONS: For exogenous CSP, when the thickness of cesarean scar is <= 3 mm, whether or not undertaking UAE, it should be seen as contraindication of hysterscopic surgery. UAE combined with hysterscopic surgery for the treatment of exogeous CSP with the cesarean scar thickness > 3 mm is safe and feasible according to patients condition and should be performed by experienced hysteroscopist. PMID- 26675181 TI - [Incidence and management of monozygotic twin conceived by assisted reproductive techniques]. AB - OBJECTIVE: To analysis the incidence and management of monozygotic twin (MZT) conceived by assisted reproductive techniques (ART). METHODS: A retrospective analysis of clinical pregnancies and MZT that resulted from ART was performed in Reproductive Medical Center, the First Affiliated Hospital, Wenzhou Medical University between January 2011 and January 2014. RESULTS: A total of 5 908 pregnancies were diagnosed: 2 012 twins, 157 high-order multiple pregnancy (HOMP), including 4 quadruplets. Overall, 51 MZT pregnancies were identified of them including 32 cases HOMP and 19 cases MZT. The incidence of MZT resulting from cleavage-stage embryo transfer was similar to blastocyst transfer (P = 0.960). The percent of MZT resulting from in vitro fertilization [0.93% (28/3 022)], frozen-thawed embryo transfer [0.87% (13/1 502)] and intracytoplamic sperm injection [0.72% (10/1 384)] did not show statistical significance (P = 0.794). The expectantly managed MZT was associated with a significantly greater likelihood of miscarriage [6/19 vs 5.11% (101/1 976)], and low birth weight infant [73.91% (17/23) vs 42.89% (1 453/3 388), P < 0.01], when compared with dizygotic twin (DZT) did not undergo selective embryo reduction (SER). In monozygotic (MZ)-triplets with SER to 2 fetuses or to 1 fetus, there was no cases of preterm birth or low birth weight infant observed in MZ-triplets with SER to 1 fetus; when compared with MZ-triplets with SER to 2 fetuses, the low birth weight infant [56.00% (14/25), P = 0.021] has statistical significance. The likelihood of the survival of two babies was lower in MZ-triplets with SER to 2 fetuses when compared with non-MZ triplets with SER to 2 fetuses [42.86% (9/21) vs 75.21% (91/121), P = 0.003]. CONCLUSIONS: The incidence of MZT pregnancies following ART is high. It plays a significant role in the occurrence of HOMP. MZT pregnancies are at an increased risk of adverse outcomes, it should transform to a single embryo thansfer (SET) program to reduce them incideuce. Reduction of MZT contained in multiple pregnancies appears to be a safe option. PMID- 26675180 TI - [Analysis of 43 cases of cesarean scar pregnancy treated with suction curettage under ultrasound guidance]. AB - OBJECTIVE: To evaluate the feasibility and safety of transabdominal ultrasound guided suction curettage to treat cesarean scar pregnancy (CSP) and investigate factors affecting prognosis of CSP. METHODS: This was a retrospective case study of 43 cases who were diagnosed as CSP and treated by suction curettage under transabdominal ultrasound guidance as an initial treatment of CSP in Obstetrics and Gynecology Hospital of Fudan University over past 7 years (from 2007 to 2013); factors affecting prognosis of CSP were investigated. RESULTS: 39 of the 43 cases (91%) were successfully treated. There were no statistically significant differences in maternal age, gravidity, abortion frequency, and the time interval between current CSP and last cesarean delivery, the myometrium thickness between the gestational sac and the bladder wall between the success group and the failure group (all P > 0.05). Statistically significant difference was found in crown-rump length (CRL) between the two group (median of the two group was 18.5, 2.0 mm) by rank sum test (P = 0.047). Univariate logistic regression analysis demonstrated that CRL was strongly associated with the prognosis and the OR for no complications was 18.50, comparing CRL <= 6 mm versus CRL > 6 mm (P = 0.020). CONCLUSION: Transabdominal ultrasound-guided suction curettage is effective and safe in the treatment of CSP with CRL <= 6 mm. PMID- 26675182 TI - [Change tendency during 30 years of infertility and endometriosis in Peking Union Medical College Hospital]. AB - OBJECTIVE: To analyze the incidence of endometriosis in inpatients with infertility in Peking Union Medical College Hospital in 30 years. METHODS: The inpatients of Peking Union Medical College Hospital admitted between May 1983 and November 2013 was searched. The infertile patients receiving laparoscopy or laparotomy were included. The discharge diagnosis and the operation were summarized. The incidence of gynecologic diseases were demonstrated, such as endometriosis, pelvic adhesions, uterine fibroid, hydrosalpinx, ovarian benign tumor, and adenomyosis. The age was collected, and the change of age and the incidence of endometriosis was analyzed. RESULTS: The incidence of endometriosis in infertile female inpatients was 35.50% (95% CI: 34.50%-36.49%). The incidence showed relatively stable increasing tendency after 2004 (with P < 0.01). The age had increased significantly since 1996 (with P < 0.01); the average age was (29.76 +/- 3.74) years old in 1996, and (32.85 +/- 4.49) years old in 2013 (P < 0.01). The inpatients diagnosed with endometriosis had greater age, (32.67 +/- 4.06) versus (32.04 +/- 4.55) years old (P < 0.01); the incidence of endometriosis differed in different age group, the older group had higher incidence (chi2 = 85.807, P < 0.01). CONCLUSIONS: Infertile female inpatients showed increasing incidence of endometriosis in recent years. Older infertile patients maybe have higher risk of endometriosis. PMID- 26675183 TI - [Investigation of individualized treatment based on sentinel lymph node biopsy for early-stage vulvar cancer]. AB - OBJECTIVE: To evaluate the feasibility and outcomes of different surgical approaches on the basis of sentinel lymph node biopsy (SLNB) in treating early stage vulvar cancer, and discuss the proper strategy for individualized treatment. METHODS: The medical charts of patients with early-stage vulvar cancer treated in Sun Yat-sen University between January 2004 and December 2013 were retrospectively collected. A total of 74 patients who received sentinel lymph node (SLN) detection in primary surgery were enrolled (average age 55). The surgical approaches contained SLNB, inguinal lymphadenectomy (IL), and extensive vulvectomy. The SLN were examed on intraoperative frozen sections. The treatment protocols, lymphatic metastasis, postoperative recovery condition, recurrence and survival data were collected and analyzed. RESULTS: At least one SLN was successfully detected in 68 (92%, 68/74) patients. SLN were positive in 21 patients, of whom 12 (group A) underwent bilateral IL, and 9 (group B) received radiotherapy without performed IL. SLN were negative in 47 patients, of whom 26 (group C) underwent bilateral IL and one of them had a non-SLN metastasis, and 21 (group D) were advised to follow-up. The coincidence of pathological results between frozen and paraffin sections was 100%. The sensitivity and specificity of SLNB for diagnosis of lymph node metastasis were 95% and 100%, respectively. A total of 44 complications happened in patients underwent SLNB and IL (group A and C), including 16 poor wound healing, 14 lymphedema, 8 lymphatic fistulas, 3 phlebothrombosis and 3 infections. There were no complications happened in patients underwent SLNB alone (group B and D), among whom the operation time, bleeding amount, and hospital stay were also significantly less than those in patients underwent SLNB and IL. The median follow-up time was 41 months and the 3 year overall survival rate was 85% in the whole series. Recurrences were observed in 11 patients and 9 of them died of the tumor with the median survival time of 15 months. In patients with positive SLN (group A and B), the 3-year overall survival rate was 58% with 8 patients died of the disease, including 4 in group A and 4 in group B. In patients with negative SLN (group C and D), the 3-years overall survival rate was 97% with one patient in group D died of the tumor, and significantly higher than that of patients with positive SLN (P = 0.003). The 3 year overall survival rate was significantly difference. In univariate analysis by log-rank test showed that, neither in patients with nor without SLN metastasis the prognosis differed with respect to surgical approaches (group A vs B, P = 0.709; group C vs D, P = 0.253). Univariate analysis by log-rank test showed that, lymph node metastasis, pathological grade, depth of invasion, and tumor location could significantly affected survival (P < 0.05), whereas age, tumor diameter, and surgical approach didn't (P > 0.05). Multivariate analysis showed that lymph node metastasis (RR = 21.57, 95% CI: 2.68-173.10, P = 0.002) and tumor location (RR = 7.85, 95% CI: 1.79-34.50, P = 0.024) were the independent factors for overall survival. CONCLUSIONS: Lymph node metastasis is an independent prognosis factor for patients with early-stage vulvar cancer. SLNB could accurately diagnose the status of lymph nodes and help to decide subsequent treatment. The omissions of IL in patients with negative SLN avoid surgical morbidity and shorten postoperative recovery period without an increased risk of recurrence. PMID- 26675184 TI - [Robotic surgery in the management of early ovarian malignancy tumors]. AB - OBJECTIVE: To apply robotic surgery of early ovarian malignancy tumors clinically and evaluate its feasibility in management for early ovarian cancer. METHODS: Using the da Vinci robotic surgical system, seven patients with early ovarian malignancy tumors (stage I) underwent robotic surgery from April 2012 to September 2013. The average age was 45.7 years. Robotic surgeries approaches contained salpingo-oophorectomy, para-aortic lymphadenectomy, pelvic lymphadenectomy, omentectomy and appendectomy. Perioperative and follow-up clinical data were recorded. RESULTS: All robotic surgeries were successfully completed without the conversion to laparotomy. The mean operative time was 225 minutes (100-330 minutes). The average estimated blood loss was 171 ml (20-600 ml). No patients received blood transfusions. No intraoperative and postoperative complications were observed. The average number of pelvic lymph node dissected were 18.3 (11-34). The average number of para-aortic lymph node dissected were 3.7 (3-4). The mean follow-up time was 26.0 months after surgery (20-36 months). Currently, all patients had no tumor recurrence and survived. CONCLUSION: Robotic surgery is feasible as a novel alternative approach in the treatment of early ovarian malignancy tumors. PMID- 26675185 TI - [Relationship between the expression of chemokines and their receptors in the maternal-fetal interface and pathogenesis of unexplained recurrent spontaneous abortion]. AB - OBJECTIVE: To explore the relationship between the expression of chemokines and their receptors in the maternal-fetal interface and the pathogenesis of unexplained recurrent spontaneous abortion (URSA). METHODS: 8-10 weeks CBA/J female mice were mated with DBA/2 and BALB/c male mice at the ratio of 2:1 to establish the model of normal pregnant mice (CBA/J * BALB/c) and URSA mice (CBA/J * DBA/2). Sixty mice were divided into 6 groups, with ten in each group. The mice in the normal unpregnancy group were executed for endometrial tissues; the mice in the embryonic implantation normal pregnancy group were executed for endometrial tissues at the sixth day of gestation; the mice in the embryonic development normal pregnancy group were executed for decidua and chorionic tissues at the fourteenth day of gestation. While, the mice in the embryonic implantation URSA group were executed for endometrial tissues at the sixth day of gestation; the mice in the pre-abortion URSA group were executed for decidua and chorionic tissues at the ninth day of gestation; the mice in the post-abortion URSA group were executed for decidua and chorionic tissues at the fourteenth day of gestation. The chemokines and their receptors in different tissues of the mice were determined by western blot, including the protein expression of stromal cell derived factor (CXCL12), monocyte chemotactic protein 1 (CCL2), regulated upon activation normal T cell expressed and secreted (RANTES) and their receptor CXCR4, CCR2, CCR5 in maternal-fetal interface. RESULTS: (1) The protein expression of CXCL12 and CXCR4, CCL2 and CCR2, RANTES and CCR5 in endometrial tissues of the normal unpregnant group were 0.13 +/- 0.04 and 0.18 +/- 0.09, 0.057 +/- 0.023 and 0.39 +/- 0.08, 0.034 +/- 0.012 and 0.22 +/- 0.05, respectively. They were 0.35 +/- 0.09 and 0.93 +/- 0.15, 0.349 +/- 0.056 and 0.91 +/- 0.15, 0.336 +/- 0.089 and 0.44 +/- 0.05 in endometrial tissues in the embryonic implantation normal pregnancy group; and were 0.62 +/- 0.15 and 1.23 +/ 0.28, 0.283 +/- 0.051 and 0.55 +/- 0.09, 0.225 +/- 0.065 and 0.35 +/- 0.07 in decidua tissues in the embryonic development normal pregnancy group. The protein expression of chemokines and their receptors in endometrial tissues in the embryonic implantation normal pregnancy group and in decidua tissues in the embryonic development normal pregnancy group were higher than those in the normal unpregnancy group, with statistically significant difference (P < 0.05). Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 in decidual tissues in the embryonic development normal pregnancy group were significantly higher (P < 0.05), while CCL2 and CCR2, RANTES and CCR5 were significantly lower (P < 0.05). (2) Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 (0.20 +/- 0.06 and 0.44 +/- 0.11) in endometrial tissues in the embryonic implantation URSA group were significantly lower (P < 0.01), while CCL2 and CCR2 (0.451 +/- 0.133 and 1.32 +/- 0.20), RANTES and CCR5 (0.488 +/- 0.137 and 0.61 +/- 0.18) were higher (P < 0.05). (3) Compared with the embryonic development normal pregnancy group, CXCL12 and CXCR4 in decidual tissues of pre-abortion URSA group (0.27 +/- 0.09 and 0.26 +/- 0.10), post-abortion URSA group (0.25 +/- 0.08 and 0.23 +/- 0.08) were significantly lower (P < 0.01), while CCL2 and CCR2 (0.576 +/- 0.123 and 0.92 +/- 0.15 in the pre-abortion URSA group; 0.748 +/- 0.112 and 1.56 +/- 0.34 in the post-abortion URSA group), RANTES and CCR5 (0.294 +/- 0.054 and 0.59 +/- 0.18 in the pre abortion URSA group; 0.363 +/- 0.058 and 0.78 +/- 0.14 in the post-abortion URSA group) were significantly higher (P < 0.05). CCL2 and CCR2, RANTES and CCR5 in decidual tissues in the post-abortion URSA group was obviously higher than those of the pre-abortion URSA group, with statistically significant difference (P < 0.05). CONCLUSIONS: The accurate expression of CXCL12, CCL2, RANTES and their receptors CXCR4, CCR2, CCR5 play important roles in the embryonic implantation and development. The lower expression of CXCL12 and CXCR4 protein and higher expression of CCL2 and CCR2, RANTES and CCR5 in decidua and chorionic tissues are closely related to the pathogenesis of URSA. PMID- 26675187 TI - Coaching to Augment Mentoring to Achieve Faculty Diversity: A Randomized Controlled Trial. AB - PURPOSE: The Academy for Future Science Faculty (the Academy) is a novel coaching intervention for biomedical PhD students designed to address limitations in previous efforts to promote faculty diversity. Unlike traditional research mentoring, the Academy includes both group and individual coaching, coaches have no research or evaluation roles with the students, and it is based on social science theories. The authors present a qualitative case study of one of the coaching groups and provide statistical analyses indicating whether one year in the Academy effects students' perceptions of the achievability and desirability of an academic career. METHOD: The authors tested (July 2012-July 2013), with Northwestern University ethical approval, the Academy via a longitudinal randomized controlled trial. Participants were 121 latter-stage biomedical PhD students. The authors collected data via questionnaires, interviews, and meeting recordings. RESULTS: The case study shows how group career coaching can effectively supplement traditional one-to-one research mentoring; provide new role models for underrepresented minority students; and provide theory-based lenses through which to engage in open conversations about race, gender, and science careers. Repeated-measures analysis of variance showed that perceived achievability increased in the Academy group from baseline to one-year follow-up (mean, 5.75 versus 6.39) but decreased in the control group (6.58 versus 5.81). Perceived desirability decreased significantly less (P < .05) in the Academy group (7.00 versus 6.36) than in the control group (7.83 versus 5.97). CONCLUSIONS: Early results suggest that an academic career coaching model can effectively supplement traditional research mentoring and promote persistence toward academic careers. PMID- 26675186 TI - Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis. AB - A better understanding of the kinetics of accumulated immune cells that are involved in pathophysiology during Mycobacterium tuberculosis (Mtb) infection may help to facilitate the development of vaccines and immunological interventions. However, the kinetics of innate and adaptive cells that are associated with pathogenesis during Mtb infection and their relationship to Mtb virulence are not clearly understood. In this study, we used a mouse model to compare the bacterial burden, inflammation and kinetics of immune cells during aerogenic infection in the lung between laboratory-adapted strains (Mtb H37Rv and H37Ra) and Mtb K strain, a hyper-virulent W-Beijing lineage strain. The Mtb K strain multiplied more than 10- and 3.54-fold more rapidly than H37Ra and H37Rv, respectively, during the early stage of infection (at 28 days post-infection) and resulted in exacerbated lung pathology at 56 to 112 days post-infection. Similar numbers of innate immune cells had infiltrated, regardless of the strain, by 14 days post infection. High, time-dependent frequencies of F4/80-CD11c+CD11b-Siglec-H+PDCA-1+ plasmacytoid DCs and CD11c-CD11b+Gr-1int cells were observed in the lungs of mice that were infected with the Mtb K strain. Regarding adaptive immunity, Th1 and Th17 T cells that express T-bet and RORgammat, respectively, significantly increased in the lungs that were infected with the laboratory-adapted strains, and the population of CD4+CD25+Foxp3+ regulatory T cells was remarkably increased at 112 days post-infection in the lungs of mice that were infected with the K strain. Collectively, our findings indicate that the highly virulent Mtb K strain may trigger the accumulation of pDCs and Gr1intCD11b+ cells with the concomitant down-regulation of the Th1 response and the maintenance of an up-regulated Th2 response without inducing a Th17 response during chronic infection. These results will help to determine which immune system components must be considered for the development of tuberculosis (TB) vaccines and immunological interventions. PMID- 26675188 TI - The Changing Nature of Scientific Sharing and Withholding in Academic Life Sciences Research: Trends From National Surveys in 2000 and 2013. AB - PURPOSE: Since 2000, federal funders and many journals have established policies requiring more open sharing of data and materials post-publication, primarily through online supplements and third-party repositories. This study examined changes in sharing and withholding practices among academic life scientists, particularly geneticists, between 2000 and 2013. METHOD: In 2000 and 2013, the authors surveyed separate samples of 3,000 academic life scientists at the 100 U.S. universities receiving the most National Institutes of Health funding. Respondents were asked to estimate the number of requests for information, data, and materials they made to and received from other academic researchers in the past three years. They were also asked about potential consequences of sharing and withholding. RESULTS: Response rates were 63.9% (1,849/2,893) in 2000 and 40.8% (1,165/2,853) in 2013. Proportions of faculty in 2000 and 2013 who received, denied, made, or were denied at least one request were not statistically different. However, the total volume of requests received from or made to other scientists dropped substantially (19.4 received in 2000 versus 10.8 in 2013, P < .001; 8.4 made in 2000 versus 6.6 in 2013, P < .001). Faculty in 2013 also made an average of 8.4 requests to third-party repositories. Researchers in 2013 were less likely to report sharing resulted in new research or collaborations. CONCLUSIONS: The results show a dramatic shift in sharing mechanisms, away from a peer-to-peer sharing model toward one based on central repositories. This may increase efficiency, but collaborations may suffer if personal communication among scientists is deemphasized. PMID- 26675189 TI - Advancing Competency-Based Medical Education: A Charter for Clinician-Educators. AB - The International Competency-Based Medical Education (ICBME) Collaborators have been working since 2009 to promote understanding of competency-based medical education (CBME) and accelerate its uptake worldwide. This article presents a charter, supported by a literature-based rationale, which is meant to provide a shared mental model of CBME that will serve as a path forward in its widespread implementation.At a 2013 summit, the ICBME Collaborators laid the groundwork for this charter. Here, the fundamental principles of CBME and professional responsibilities of medical educators in its implementation process are described. The authors outline three fundamental principles: (1) Medical education must be based on the health needs of the populations served; (2) the primary focus of education and training should be the desired outcomes for learners rather than the structure and process of the educational system; and (3) the formation of a physician should be seamless across the continuum of education, training, and practice.Building on these principles, medical educators must demonstrate commitment to teaching, assessing, and role modeling the range of identified competencies. In the clinical setting, they must provide supervision that balances patient safety with the professional development of learners, being transparent with stakeholders about level of supervision needed. They must use effective and efficient assessment strategies and tools for basing transition decisions on competence rather than time in training, empowering learners to be active participants in their learning and assessment. Finally, advancing CBME requires program evaluation and research, faculty development, and a collaborative approach to realize its full potential. PMID- 26675190 TI - Protocol Standards for Reporting Video Data in Academic Journals. AB - Editors of biomedical journals have estimated that a majority (40%-90%) of studies published in scientific journals cannot be replicated, even though an inherent principle of publication is that others should be able to replicate and build on published claims. Each journal sets its own protocols for establishing "quality" in articles, yet over the past 50 years, few journals in any field- especially medical education--have specified protocols for reporting the use of video data in research. The authors found that technical and industry-driven aspects of video recording, as well as a lack of standardization and reporting requirements by research journals, have led to major limitations in the ability to assess or reproduce video data used in research. Specific variables in the videotaping process (e.g., camera angle), which can be changed or be modified, affect the quality of recorded data, leading to major reporting errors and, in turn, unreliable conclusions. As more data are now in the form of digital videos, the historical lack of reporting standards makes it increasingly difficult to accurately replicate medical educational studies. Reproducibility is especially important as the medical education community considers setting national high stakes standards in medicine and surgery based on video data. The authors of this Perspective provide basic protocol standards for investigators and journals using video data in research publications so as to allow for reproducibility. PMID- 26675191 TI - Transforming Medical Education: Is Competency-Based Medical Education the Right Approach? AB - There is growing recognition within the medical education community that medical education in this country needs to be changed to better prepare doctors for the challenges they will face in providing their patients high-quality medical care. A competency-based medical education (CBME) approach was endorsed by the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties approximately 15 years ago, and a self-designated group-the International Competency-Based Medical Education (ICBME) Collaborators-is now calling on members of the medical education community to join them in their effort to establish CBME as the approach to be used in transforming medical education, not only in the United States but also around the world.In response to an article in this issue by a group of ICBME Collaborators, the author argues that more evidence about the effectiveness of CBME is needed before a global shift to this approach is undertaken. It is time for major organizations and foundations that are committed to improving medical education to step forward and take the lead in partnering with the medical education community to conduct a critical evaluation of CBME. In addition, maintenance of certification, relicensure, and continuing medical education programs should be evaluated for their effectiveness in ensuring that physicians are clinically competent not only at the beginning of their career but also until the end. PMID- 26675192 TI - Three-Year Experience of an Academic Medical Center Ombuds Office. AB - An ombuds is an individual who informally helps people or groups (visitors) resolve disputes and/or interpersonal conflicts as an alternative to formal dispute resolution mechanisms within an organization. Ombuds are nearly ubiquitous in many governmental, business, and educational settings but only recently have gained visibility at medical schools. Medical schools in the United States are increasingly establishing ombuds offices as part of comprehensive conflict management systems to address concerns of faculty, staff, students, and others. As of 2015, more than 35 medical schools in the United States have active ombuds Web pages. Despite the growing number of medical schools with ombuds offices, the literature on medical school ombuds offices is scant. In this article, the authors review the first three years of experience of the ombuds office at the Medical College of Wisconsin, a freestanding medical and graduate school with a large physician practice. The article is written from the perspective of the inaugural ombuds and the president who initiated the office. The authors discuss the rationale for, costs of, potential advantages of, and initial reactions of faculty, staff, and administration to having an ombuds office in an academic medical center. Important questions relevant to medical schools that are considering an ombuds office are discussed. The authors conclude that an ombuds office can be a useful complement to traditional approaches for conflict management, regulatory compliance, and identification of systemic issues. PMID- 26675193 TI - 116E rotavirus vaccine may have less impact in India than projected. PMID- 26675194 TI - Evaluation of rotavirus disease burden and vaccine effectiveness in India. PMID- 26675195 TI - Answer to the question from page 105. PMID- 26675196 TI - Role of Conservative Management in Emphysematous Pyelonephritis - A Retrospective Study. AB - INTRODUCTION: Emphysematous pyelophritis (EPN) is a serious condition with significant mortality. The prognosis of patients with EPN has changed over the years. Mortality has declined with prompt and aggressive medical management and minimally invasive strategies. AIM: To identify the prognostic factors and assess the outcome of conservative management of emphysematous pyelonephritis. SETTINGS AND DESIGN: This was a retrospective study of 8 consecutive patients who were diagnosed with EPN in two medical institutes between July 2010 and June 2015. MATERIALS AND METHODS: Eight consecutive patients diagnosed with emphysematous pyelonephritis between July 2010 and June 2015 was studied retrospectively. On the basis of Computerised tomographic scan findings they were grouped into four classes (1 to 4) according the modified classification recommended by Huang and Tseng. The management was conservative (combination of percutaneous drainage and antibiotics), immediate nephrectomy or delayed nephrectomy (when conservative management failed). Demographic, clinical, biochemical and radiological characteristics were assessed and compared between survivors and nonsurvivors. RESULTS: Seven (87.5%) of a total of 8 patients had diabetes mellitus. Escherichia coli (71.4 %) was the most common offending pathogen identified in pus culture. With conservative management in 7 patients (combination of percutaneous drainage and antibiotics), treatment was successful in 57.14 % and with immediate nephrectomy (one patient), the success rate was 100%. The risk factors for mortality were thrombocytopenia, shock and altered sensorium at presentation. The mortality rate in class 1, 2 and 3 was 0%, 33.3% and 66.7%. None of the patient had class 4 EPN. CONCLUSION: A combination of percutaneous drainage with antibiotics offers an effective therapy for emphysematous pyelonephritis. PMID- 26675197 TI - Comments on the 2015 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-segment Elevation. AB - Patients who have undergone angioplasty with stenting can be reintegrated into normal life at an early stage, thanks to the absence of sequelae associated with the procedure itself. Consequently, these patients can be involved earlier in the second stage of cardiac rehabilitation. Although rehabilitation for coronary patients follows the general guidelines used for all patients, which were developed with the secondary prevention of coronary artery atherosclerosis in mind, the specific form of rehabilitation adopted for each individual with ischemic heart disease will depend on the patient's circumstances, including the revascularization technique used. Regular physical exercise (i.e. physical training), in itself, has substantial cardiovascular benefits for both primary and secondary cardiovascular prevention. In patients who have had a myocardial infarction, training decreases mortality, increases functional capacity and improves ventricular function and remodeling. It is also thought to boost the collateral circulation. In addition, training improves endothelial function and stimulates the circulation of stem cells. It has been shown that physical training after percutaneous revascularization decreases the number of cardiac events. Moreover, in patients with stable angina, it results in fewer events than percutaneous revascularization. PMID- 26675198 TI - Comments on the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases. A Report by the Spanish Society of Cardiology Guidelines Committee Working Group. PMID- 26675199 TI - 2015 ESC Guidelines for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-segment Elevation. PMID- 26675200 TI - 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases. AB - Full text available at: http://eurheartj.oxfordjournals.org/content/early/2015/08/28/eurheartj.ehv318. PMID- 26675203 TI - TBAI-Catalyzed Reaction between N-Tosylhydrazones and Sulfur: A Procedure toward 1,2,3-Thiadiazole. AB - A TBAI-catalyzed reaction between N-tosyl hydrazone and sulfur was developed, leading to 1,2,3-thiadiazoles in moderate to good yields. It represents a facile and practical procedure to access thiadiazole under metal-free conditions. This procedure serves as an improvement for the Hurd-Mori reaction. PMID- 26675204 TI - Impact of farm modernity on the prevalence of chronic obstructive pulmonary disease in dairy farmers. AB - Dairy farming is associated with an excess of chronic obstructive pulmonary disease (COPD). The dairy industry has been changing for the past three decades with larger, more efficient farms and potentially less exposure to agents involved in COPD development. However, the impact of farm modernisation on COPD prevalence is unknown. We studied respiratory symptoms, respiratory function by spirometry and tobacco smoking in 575 male dairy farmers working either in traditional or in modern farms in the French Doubs region. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70) and by the Quanjer reference equation (FEV1/FVC100 mg/m2 and <=200 mg/m2), and high- (cumulative dose>200 mg/m2) dose groups. Subgroups of patients included pre-treatment levels of Epstein-Barr Virus DNA (EBV DNA)<4000 copies/ml and pre-treatment EBV DNA>=4000 copies/ml. To test for independent significance, the Kaplan-Meier with the log-rank test and the Cox proportional hazards model were used. RESULTS: The 5-year overall survival (OS) rates of the low-, medium-, and high-dose groups were 64.1%, 91.1%, and 89.4%, respectively (P=0.002). Based on multivariate analysis, patients who were in the medium- and high-dose groups had compared with the low-dose group, with an odds ratio of 0.135 (95% CI 0.045 0.405, P<0.001) and 0.225 (95% CI 0.069-0.734, P=0.013), respectively. For the low-risk patients, the cumulative dose of cisplatin significantly associated with a lower OS (P<0.001). The medium-dose group had reduced odds of death compared with the low-dose group, with an odds ratio of 0.062 (95% CI 0.001-0.347, P=0.002), according to multivariate analysis. CONCLUSIONS: The cumulative dose of cisplatin is associated with OS and distant metastasis-free survival (DMFS) among NPC patients who received IMRT. PMID- 26675211 TI - 5'-C-Malonyl RNA: Small Interfering RNAs Modified with 5'-Monophosphate Bioisostere Demonstrate Gene Silencing Activity. AB - 5'-Phosphorylation is a critical step in the cascade of events that leads to loading of small interfering RNAs (siRNAs) into the RNA-induced silencing complex (RISC) to elicit gene silencing. 5'-Phosphorylation of exogenous siRNAs is generally accomplished by a cytosolic Clp1 kinase, and in most cases, the presence of a 5'-monophosphate on synthetic siRNAs is not a prerequisite for activity. Chemically introduced, metabolically stable 5'-phosphate mimics can lead to higher metabolic stability, increased RISC loading, and higher gene silencing activities of chemically modified siRNAs. In this study, we report the synthesis of 5'-C-malonyl RNA, a 5'-monophosphate bioisostere. A 5'-C-malonyl modified nucleotide was incorporated at the 5'-terminus of chemically modified RNA oligonucleotides using solid-phase synthesis. In vitro silencing activity, in vitro metabolic stability, and in vitro RISC loading of 5'-C-malonyl siRNA was compared to corresponding 5'-phosphorylated and 5'-nonphosphorylated siRNAs. The 5'-C-malonyl siRNAs showed sustained or improved in vitro gene silencing and high levels of Ago2 loading and conferred dramatically improved metabolic stability to the antisense strand of the siRNA duplexes. In silico modeling studies indicate a favorable fit of the 5'-C-malonyl group within the 5'-phosphate binding pocket of human Ago2MID domain. PMID- 26675212 TI - Multiple renal angiomyolipomata. A case report. AB - We present a 76-year-old patient with multiple renal angiomylipoma in one kidney. The patient had not been having any urinary tract symptoms, the lesions in kidney were visualized in US examination performed because of cholelithiasis suspicion. Angiomyolipoma is included to the benign tumors of hamartoma group and its growth is related to the hormonal activity of the organism. Multiple renal angiomyolipomata, occurring very rarely, are usually related to the tuberous sclerosis syndrome (Bourneville-Pringle disease). The nature of this disease is the occurrence of multiple hamartoma type tumors in the skin, brain, kidneys, heart, bones, lungs and eyes. Small renal angiomyolipomata are asymptomatic and are usually accidentally diagnosed during imaging examinations, big ones may be the reason of significant ailments. Among severe, life threatening complications of renal angiomyolipoma one can number bleeding from the tumor. Bleeding risk depends on the tumor diameter and significantly increases in tumors of the diameter above 4 cm. Computed tomography is an imaging method recommended for the assessment of hemorrhagic complications in angiomyolipoma. The check-up frequency depends on the tumor diameter - in tumors smaller than 4 cm the examination is performed once yearly, in tumors greater than 4 cm - every 6 months. In the treatment of hemorrhagic complications of angiomyolipoma, a surgical treatment (partial or radical nephrectomy) or renal vessel embolization is used. Renal arteriography with embolization is an important therapeutic method to control the bleeding and to avoid surgery. PMID- 26675213 TI - Intra-cellular bacterial infections affect learning and memory capacities of an invertebrate. AB - BACKGROUND: How host manipulation by parasites evolves is fascinating but challenging evolutionary question remains. Many parasites share the capacity to manipulate host behavior increasing their transmission success. However, little is known about the learning and memory impact of parasites on their host. Wolbachia are widespread endosymbionts and infect most insect species. These bacteria are maternally transmitted and mainly alter the reproduction of hosts with weak virulence. We tested the impact of parasites (Wolbachia) on their host learning and memory capacities. To address this question we trained individuals to one direction with positive reinforcement. We compared performances between individual Wolbachia-free, Wolbachia naturally and Wolbachia artificially infected individuals. RESULTS: We report that in the host parasite interaction (Armadillidium vulgare/Wolbachia) naturally infected individuals Wolbachia or transinfected adult with Wolbachia are less likely to learn and memorize the correct direction with social reinforcement compared to Wolbachia-free individuals. CONCLUSIONS: Our results imply that Wolbachia impact in the central nervous system of their host altering the memory formation and maintenance. We conclude that host manipulation can affect cognitive processes decreasing host adaptation capacities. PMID- 26675214 TI - Phylogenetic and Evolutionary Analyses of the Frizzled Gene Family in Common Carp (Cyprinus carpio) Provide Insights into Gene Expansion from Whole-Genome Duplications. AB - In humans, the frizzled (FZD) gene family encodes 10 homologous proteins that commonly localize to the plasma membrane. Besides being associated with three main signaling pathways for cell development, most FZDs have different physiological effects and are major determinants in the development process of vertebrates and. Here, we identified and annotated the FZD genes in the whole genome of common carp (Cyprinus carpio), a teleost fish, and determined their phylogenetic relationships to FZDs in other vertebrates. Our analyses revealed extensive gene duplications in the common carp that have led to the 26 FZD genes that we detected in the common carp genome. All 26 FZD genes were assigned orthology to the 10 FZD genes of on-land vertebrates, with none of genes being specific to the fish lineage. We postulated that the expansion of the FZD gene family in common carp was the result of an additional whole genome duplication event and that the FZD gene family in other teleosts has been lost in their evolution history with the reason that the functions of genes are redundant and conservation. Through the expression profiling of FZD genes in common carp, we speculate that the ancestral gene was likely capable of performing all functions and was expressed broadly, while some descendant duplicate genes only performed partial functions and were specifically expressed at certain stages of development. PMID- 26675216 TI - Foreword to the Special Issue of Ultrasonic Imaging on Biomedical Imaging with Combined Light and Sound. PMID- 26675215 TI - How did partners experience cancer patients' participation in a phase I study? An observational study after a patient's death. AB - OBJECTIVE: It can be assumed that patients' participation in a phase I study will have an important impact on their partners' life. However, evaluation of partners' experiences while patients are undergoing experimental treatment and of their well-being after the patient's death is lacking. We aimed to explore partners' experience of patients' participation in phase I studies and to investigate their well-being after a patient's death. METHOD: This was an observational study conducted after the patient's death. Partners of deceased patients who had participated in a phase I study completed a questionnaire designed by us for experience evaluation and the Beck Depression Inventory for Primary Care, the Hospital Anxiety and Depression Scale, the Inventory of Traumatic Grief, and the RAND-36 Health Survey. RESULTS: The median age of the 58 participating partners was 58 years (range: 51-65), and 67% was female. Partners reported negative effects on patients' quality of life, but only 5% of partners regretted patients' participation. Approximately two years after the patients' death, 19% of partners scored for depression, 36% for psychological distress, and 46% for complicated grief, and partners generally scored significantly lower on social and mental functioning compared to normative comparators. SIGNIFICANCE OF RESULTS: Although partners reported negative consequences on patients' quality of life, most did not regret patients' participation in the phase I studies. Prevalence of depression, psychological distress, and complicated grief seemed important problems after a patient's death, and these must be considered when shaping further support for partners of patients participating in phase I trials. PMID- 26675217 TI - Relevant Physicochemical Descriptors of "Soft Nanomedicines" to Bypass Biological Barriers. AB - Herein, we present an overview on the current status of the characterization techniques and methodologies used to study the physicochemical descriptors that influence the final clinical performance of a given nanomedicine. The described techniques were selected based on their suitability to operate under relevant "native" conditions that mimic the physiological environment. Special emphasis is placed on those techniques that hold a greater potential to unravel dynamic, structural, and compositional features of soft organic nanomedicines relevant to the ability to bypass biological barriers, and hence allow for the rational design of drug delivery platforms with improved biological output. PMID- 26675218 TI - The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery. AB - For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers. PMID- 26675219 TI - DNA-Based Drug Carriers: The Paradox of a Classical "Cargo" Material Becoming a Versatile "Carrier" to Overcome Barriers in Drug Delivery. AB - Drug delivery strategies help cope with drawbacks of classical pharmaceuticals, including increasing their solubility, diminishing side effects and improving biodistribution. A multitude of vehicles have been envisioned to this end, encompassing a variety of materials, architectures, and functionalities. DNA built carriers are relatively new, yet promising devices to help overcome some of the current barriers in drug delivery. Its easy fabrication, reproducibility and tunability make DNA a unique material for building devices ranging from macro scale depot systems to nano-scale vehicles tailored as nanoparticles, containers, dendrimers, tubes, etc. Although this DNA application is relatively novel and knowledge is building up, current advances suggest great potential. Intracellular delivery is a promising option, whereby access of cargoes (from small molecules to large biotherapeutics) to the cytosol has been demonstrated in many cell types, without apparent side effects or need for additional actuators. This is paradoxical since "natural" DNA cannot access cells and nucleic acids are among the most difficult cargoes to be delivered within cells; yet this property arises from engineering DNA into particular configurations. Their biocompatibility and safety also holds potential, since this natural material is biodegradable and nucleotides are biological metabolites. Using modified nucleotides and properly designing their sequence, along with classical chemical means, make it feasible to tune the stability and degradation rates of DNA devices. Taken together, although much research is still necessary to understand the in vivo behaviour of DNA-based vehicles, the design parameters ruling their optimization, and the biological pathways regulating their function, DNA represents a unique material to help in future drug delivery applications. PMID- 26675221 TI - Intracellular Drug Delivery: Mechanisms for Cell Entry. AB - Over the last half century, the delivery of pharmacologically active substances, such as synthetic drugs, natural compounds, gene material and many other pharmaceutical products, has been widely studied. Understanding the interactions of drug carriers with cells and how these interactions influence the cellular uptake is of paramount importance, since targets for many therapeutic agents against several disorders are localized in the subcellular compartments. Besides, the route of drug carrier entry (direct or via endocytosis) often defines the efficiency, kinetics and final destination of the drug itself. Although classical endocytic pathways such as phagocytosis, macropinocytosis, clathrin-mediated and caveola-dependent pathways are well characterized, their control for pharmaceutical drug delivery applications is still a challenging issue. Also, better knowledge of non-classical endocytic pathways may help optimize targeted drug delivery systems for intracellular delivery. Therefore, this review focuses on mechanisms of intracellular delivery, including direct internalization and endocytosis, as well as factors such as targeting moiety, target receptor, and size, shape, and surface properties of the drug carrier that can influence uptake process. PMID- 26675222 TI - Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy. AB - The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID- 26675223 TI - Delivery of Peptides Via the Oral Route: Diabetes Treatment by Peptide-Loaded Nanoparticles. AB - Over the last years, the interest of the pharmaceutical industry in the use of therapeutic peptides in diabetes treatment has been increased. However, these are restricted to parenteral administration. In order to mimic the natural physiological response, many efforts have been made towards oral peptide delivery in diabetes treatment. This review article aims to give an overview on the progress in the nanomedicine field towards the design and optimization of nanoparticle-based drug delivery systems capable of overcoming the harsh gastrointestinal environment and achieving an adequate bioavailability following oral administration. The reported data clearly illustrate the promise of nanomedicine for antidiabetic oral peptide delivery. PMID- 26675224 TI - Innovative formulations for controlled drug delivery to the lungs and the technical and toxicological challenges to overcome(.). AB - Inhalation of therapeutic aerosols has a long tradition and is, moreover, regarded as a safe and efficient route of drug administration to the respiratory tract. Especially, the targeting opportunities of this approach are beneficial for the treatment of numerous airway diseases. However, the rapid decay of local drug concentration and the resulting short-term duration of action of conventional medications necessitates several daily inhalations, which is clearly in conflict with a patients' convenience and compliance. Recent progress in pharmaceutical engineering has provided promising drug delivery vehicles (e.g., liposomes, nanoparticles and thermo-responsive preparations) allowing for a sustained release of the encapsulated medication at the target site. Nevertheless, aspects such as generating tailored aerosols from these formulations (including stability during aerosolization) and the choice of biocompatible excipients remain considerable challenges, which need to be addressed in order to optimize inhalation therapy. Therefore, toxicology issues raised by these novel drug delivery vehicles with respect to physicochemical and material properties and biocompatibility are described in this review. This brief overview is intended to serve as a foundation to prompt future advancement in the field of controlled drug delivery to the lungs. PMID- 26675225 TI - Ocular Drug Delivery - New Strategies for Targeting Anterior and Posterior Segments of the Eye. AB - The ocular delivery of drugs encounters several limitations because of the dynamic and static barriers of the human's eye anatomy and physiology. The poor bioavailability of drugs are mainly related to the topical administration, i.e. eye drops which is the most common drug dosage form for the treatment of eye pathologies. Precorneal factors and drug limitations related to its solubility and susceptibility for physicochemical degradation could be the main reasons for the poor permeation and uptake in the ocular mucosa. Pathologies affecting the anterior and posterior segment of the eye are thereafter difficult to be treated and, given the chronic and degenerative nature of some of these injuries, it is crucial to improve drugs therapeutic effect. Nanotechnology-based delivery systems could be a suitable approach to overcome these limitations. Some of the most important colloidal systems are highlighted in this review, such as the use of mucoadhesive polymers, prodrugs, nanogels, liposomes, microemulsions, lipid and polymeric nanoparticles, cyclodextrins, dendrimers and nanocrystals, along with their clinical and therapeutic relevance for the administration of drugs for ocular delivery. PMID- 26675226 TI - Carrier Deformability in Drug Delivery. AB - Deformability is a key property of drug carriers used to increase the mass penetration across the skin without disrupting the lipid barrier. Highly deformable vesicles proved to be more effective than conventional liposomes in delivering drugs into and across the mammalian skin upon topical non occlusive application. In the past five years, highly deformable vesicles have been used for local delivery of drugs on joint diseases, skin cancer, atopic dermatitis, would healing, psoriasis, scar treatment, fungal, bacteria and protozoa infections. Promising topical vaccination strategies rely also in this type of carriers. Here we provide an overview on the main structural and mechanical features of deformable vesicles, to finish with an extensive update on their latest preclinical applications. PMID- 26675220 TI - Journey to the Center of the Cell: Current Nanocarrier Design Strategies Targeting Biopharmaceuticals to the Cytoplasm and Nucleus. AB - New biopharmaceutical molecules, potentially able to provide more personalized and effective treatments, are being identified through the advent of advanced synthetic biology strategies, sophisticated chemical synthesis approaches, and new analytical methods to assess biological potency. However, translation of many of these structures has been significantly limited due to the need for more efficient strategies to deliver macromolecular therapeutics to desirable intracellular sites of action. Engineered nanocarriers that encapsulate peptides, proteins, or nucleic acids are generally internalized into target cells via one of several endocytic pathways. These nanostructures, entrapped within endosomes, must navigate the intracellular milieu to orchestrate delivery to the intended destination, typically the cytoplasm or nucleus. For therapeutics active in the cytoplasm, endosomal escape continues to represent a limiting step to effective treatment, since a majority of nanocarriers trapped within endosomes are ultimately marked for enzymatic degradation in lysosomes. Therapeutics active in the nucleus have the added challenges of reaching and penetrating the nuclear envelope, and nuclear delivery remains a preeminent challenge preventing clinical translation of gene therapy applications. Herein, we review cutting-edge peptide- and polymer-based design strategies with the potential to enable significant improvements in biopharmaceutical efficacy through improved intracellular targeting. These strategies often mimic the activities of pathogens, which have developed innate and highly effective mechanisms to penetrate plasma membranes and enter the nucleus of host cells. Understanding these mechanisms has enabled advances in synthetic peptide and polymer design that may ultimately improve intracellular trafficking and bioavailability, leading to increased access to new classes of biotherapeutics. PMID- 26675227 TI - Transdermal Drug Delivery Mediated by Microneedle Arrays: Innovations and Barriers to Success. AB - Microneedles (MN) offer a simple, minimally invasive and reduced pain alternative to hypodermic needles for drug delivery, including vaccines. Previous studies investigating the use of MN have highlighted the benefit of this technology to facilitate dermal and transdermal drug delivery. Going forward towards commercialization, it is important to consider the perceptions and acceptability that MN technology will have once available in the market. This review collects the opinions and expectations of different population groups such as children, parents, paediatricians and the general public on various MN systems. In addition, the low pain perception scores, based on a visual analog scale for MN application, should also lead to a greater acceptability of this technology as a means of transdermal drug delivery. This review also highlights the potential challenges associated with the different types of MN together with issues of sterility and biocompatibility which will be important future factors to consider. PMID- 26675228 TI - Top-Down Versus Bottom-Up Nanoengineering Routes to Design Advanced Oropharmacological Products. AB - Energy intensive and chemical routes predominately govern modern dental material fabrication involving complex physicochemical approaches. Current interest in dental material design is shifting towards biomineralization method and green chemistry synthesis to support oral tissue biocompatibility and oropharmacology. This review article describes the context of biophysical approaches based on development in nanoengineering to design advance nanomaterials for clinical dentistry. We particularly focus on approaches governing surface texture and hierarchical assembly emphasis based on micro-nanoscale tooth anatomy. Further, this article provides an overview about the merit of micro-nanoscale material design techniques exchanging the traditional dental material. In this context, top-down and bottom-up approaches involving biomimetic nanoengineering route, opportunities and challenges are discussed. PMID- 26675229 TI - Fighting Diabetes: Lessons from Xenotransplantation and Nanomedicine. AB - Increasing incidence of diabetes and shortage of specific beta cells, hormonal switches like that of delta and PP cells of the islets for transplantation, have forced the scientific community to look for alternative sources through xenotransplantation and nanomedicine. The Edmonton protocol of islet transplantation has shown proof of principle of long term survival of islets in type I diabetic patients, leading to insulin prick free life. Copious volume of literature exists on the use of mammalian islets, especially of porcine origin for diabetes reversal in humans with follow-up studies upto 10 yrs. There is an obvious lack of pre-clinical results and data in the pig-to-primate model. The difficulty is in reproducing regularly the successful porcine islet isolation. Although some of the parameters have been taken, making xenotransplantation an attractive and viable alternative therapy. However, scarcity of islets is the main hurdle in the success of islet transplantation programs. Since the islet cell receptor and the insulin molecule have remained conserved throughout the evolution of vertebrates, we reviewed islet studies from other vertebrates especially, jawless fish, cartilaginous as well as bony fishes and chick islets. The similarities of chick B islets with human islets in terms of Streptozotocin insensitivity and retention of glucose responsiveness by new born chick islets tempted us to hypothesize the use of fish and chick islets as alternative sources for transplantation to reverse experimental diabetes. Since ontogeny recapitulates phylogeny, the islets recovered from lower vertebrates are likely to be less immunogenic and may open possibility of using them without immunosuppression. Complementing xenotransplantation, nanotechnology offers an excellent module for addressing the diabetes problem from detection and treatment points of view. This review attempts to throw some light on both these approaches for an effective management and cure of diabetes. PMID- 26675230 TI - Molecular mechanisms of drug photodegradation and photosensitization. AB - Drug-induced photosensitivity of the skin is drawing increasing attention. In past few decades, photosensitivity has been reported with an array of drugs, and is now recognized as a noteworthy medical problem by clinicians, regulatory authorities and pharmaceutical industry. The photosensitivity is of two types i.e., phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions, it is essential to understand the mechanism behind the photosensitizing properties of such substances before these drugs are introduced in clinical settings. Photosensitization is inter-related to photochemical reaction, through the knowledge of which the photosensitivity of a drug can be anticipated. This review highlights the current research status on photosensitizing drugs and its correlation to phototoxicity. Different mechanisms of photodegradation of photolabile drugs have also been discussed. PMID- 26664702 TI - Matching Behavior as a Tradeoff Between Reward Maximization and Demands on Neural Computation. AB - When faced with a choice, humans and animals commonly distribute their behavior in proportion to the frequency of payoff of each option. Such behavior is referred to as matching and has been captured by the matching law. However, matching is not a general law of economic choice. Matching in its strict sense seems to be specifically observed in tasks whose properties make matching an optimal or a near-optimal strategy. We engaged monkeys in a foraging task in which matching was not the optimal strategy. Over-matching the proportions of the mean offered reward magnitudes would yield more reward than matching, yet, surprisingly, the animals almost exactly matched them. To gain insight into this phenomenon, we modeled the animals' decision-making using a mechanistic model. The model accounted for the animals' macroscopic and microscopic choice behavior. When the models' three parameters were not constrained to mimic the monkeys' behavior, the model over-matched the reward proportions and in doing so, harvested substantially more reward than the monkeys. This optimized model revealed a marked bottleneck in the monkeys' choice function that compares the value of the two options. The model featured a very steep value comparison function relative to that of the monkeys. The steepness of the value comparison function had a profound effect on the earned reward and on the level of matching. We implemented this value comparison function through responses of simulated biological neurons. We found that due to the presence of neural noise, steepening the value comparison requires an exponential increase in the number of value coding neurons. Matching may be a compromise between harvesting satisfactory reward and the high demands placed by neural noise on optimal neural computation. PMID- 26675232 TI - Request for regulatory guidance for cancer cachexia intervention trials. PMID- 26675233 TI - Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane. AB - Emerin is a tail-anchored protein that is found predominantly at the inner nuclear membrane (INM), where it associates with components of the nuclear lamina. Mutations in the emerin gene cause Emery-Dreifuss muscular dystrophy (EDMD), an X-linked recessive disease. Here, we report that the TRC40/GET pathway for post-translational insertion of tail-anchored proteins into membranes is involved in emerin-trafficking. Using proximity ligation assays, we show that emerin interacts with TRC40 in situ. Emerin expressed in bacteria or in a cell free lysate was inserted into microsomal membranes in an ATP- and TRC40-dependent manner. Dominant-negative fragments of the TRC40-receptor proteins WRB and CAML (also known as CAMLG) inhibited membrane insertion. A rapamycin-based dimerization assay revealed correct transport of wild-type emerin to the INM, whereas TRC40-binding, membrane integration and INM-targeting of emerin mutant proteins that occur in EDMD was disturbed. Our results suggest that the mode of membrane integration contributes to correct targeting of emerin to the INM. PMID- 26675235 TI - Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis. AB - Weibel-Palade body (WPB)-actin interactions are essential for the trafficking and secretion of von Willebrand factor; however, the molecular basis for this interaction remains poorly defined. Myosin Va (MyoVa or MYO5A) is recruited to WPBs by a Rab27A-MyRIP complex and is thought to be the prime mediator of actin binding, but direct MyRIP-actin interactions can also occur. To evaluate the specific contribution of MyRIP-actin and MyRIP-MyoVa binding in WPB trafficking and Ca(2+)-driven exocytosis, we used EGFP-MyRIP point mutants with disrupted MyoVa and/or actin binding and high-speed live-cell fluorescence microscopy. We now show that the ability of MyRIP to restrict WPB movement depends upon its actin-binding rather than its MyoVa-binding properties. We also show that, although the role of MyRIP in Ca(2+)-driven exocytosis requires both MyoVa- and actin-binding potential, it is the latter that plays a dominant role. In view of these results and together with the analysis of actin disruption or stabilisation experiments, we propose that the role of MyRIP in regulating WPB trafficking and exocytosis is mediated largely through its interaction with actin rather than with MyoVa. PMID- 26675236 TI - Role of Securin, Separase and Cohesins in female meiosis and polar body formation in Drosophila. AB - Chromosome segregation in meiosis is controlled by a conserved pathway that culminates in Separase-mediated cleavage of the alpha-kleisin Rec8, leading to dissolution of cohesin rings. Drosophila has no gene encoding Rec8, and the absence of a known Separase target raises the question of whether Separase and its regulator Securin (Pim in Drosophila) are important in Drosophila meiosis. Here, we investigate the role of Securin, Separase and the cohesin complex in female meiosis using fluorescence in situ hybridization against centromeric and arm-specific sequences to monitor cohesion. We show that Securin destruction and Separase activity are required for timely release of arm cohesion in anaphase I and centromere-proximal cohesion in anaphase II. They are also required for release of arm cohesion on polar body chromosomes. Cohesion on polar body chromosomes depends on the cohesin components SMC3 and the mitotic alpha-kleisin Rad21 (also called Vtd in Drosophila). We provide cytological evidence that SMC3 is required for arm cohesion in female meiosis, whereas Rad21, in agreement with recent findings, is not. We conclude that in Drosophila meiosis, cohesion is regulated by a conserved Securin-Separase pathway that targets a diverged Separase target, possibly within the cohesin complex. PMID- 26675234 TI - Identification of RNF168 as a PML nuclear body regulator. AB - Promyelocytic leukemia (PML) protein forms the basis of PML nuclear bodies (PML NBs), which control many important processes. We have screened an shRNA library targeting ubiquitin pathway proteins for effects on PML NBs, and identified RNF8 and RNF168 DNA-damage response proteins as negative regulators of PML NBs. Additional studies confirmed that depletion of either RNF8 or RNF168 increased the levels of PML NBs and proteins, whereas overexpression induced loss of PML NBs. RNF168 partially localized to PML NBs through its UMI/MIU1 ubiquitin interacting region and associated with NBs formed by any PML isoform. The association of RNF168 with PML NBs resulted in increased ubiquitylation and SUMO2 modification of PML. In addition, RNF168 was found to associate with proteins modified by SUMO2 and/or SUMO3 in a manner dependent on its ubiquitin-binding sequences, suggesting that hybrid SUMO-ubiquitin chains can be bound. In vitro assays confirmed that RNF168, preferentially, binds hybrid SUMO2-K63 ubiquitin chains compared with K63-ubiquitin chains or individual SUMO2. Our study identified previously unrecognized roles for RNF8 and RNF168 in the regulation of PML, and a so far unknown preference of RNF168 for hybrid SUMO-ubiquitin chains. PMID- 26675237 TI - Haemoglobin degradation underpins the sensitivity of early ring stage Plasmodium falciparum to artemisinins. AB - Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhibitor (E64d). Quantitative modelling of the antagonism accounted for its complex dependence on the chemical features of the artemisinins and on the drug exposure time, and showed that almost all artemisinin activity in early rings (>80%) is due to haem-mediated activation. The surprising implication that haemoglobin uptake and digestion is active in early rings is supported by identification of active haemoglobinases (falcipains) at this stage. Genetic down-modulation of the expression of the two main cysteine protease haemoglobinases, falcipains 2 and 3, renders early ring stage parasites resistant to artemisinins. This confirms the important role of haemoglobin-degrading falcipains in artemisinin activation, and shows that changes in the rate of artemisinin activation could mediate high-level artemisinin resistance. PMID- 26675238 TI - WDR8 is a centriolar satellite and centriole-associated protein that promotes ciliary vesicle docking during ciliogenesis. AB - Ciliogenesis initiates at the mother centriole through a series of events that include membrane docking, displacement of cilia-inhibitory proteins and axoneme elongation. Centriolar proteins, in particular at distal and subdistal appendages, carry out these functions. Recently, cytoplasmic complexes named centriolar satellites have also been shown to promote ciliogenesis. Little is known about the functional and molecular relationship between appendage proteins, satellites and cilia biogenesis. Here, we identified the WD-repeat protein 8 (WDR8, also known as WRAP73) as a satellite and centriolar component. We show that WDR8 interacts with the satellite proteins SSX2IP and PCM1 as well as the centriolar proximal end component Cep135. Cep135 is required for the recruitment of WDR8 to centrioles. Depletion experiments revealed that WDR8 and Cep135 have strongly overlapping functions in ciliogenesis. Both are indispensable for ciliary vesicle docking to the mother centriole and for unlocking the distal end of the mother centriole from the ciliary inhibitory complex CP110-Cep97. Our data thus point to an important function of centriolar proximal end proteins in ciliary membrane biogenesis, and establish WDR8 and Cep135 as two factors that are essential for the initial steps of ciliation. PMID- 26675239 TI - WHAMY is a novel actin polymerase promoting myoblast fusion, macrophage cell motility and sensory organ development in Drosophila. AB - Wiskott-Aldrich syndrome proteins (WASPs) are nucleation-promoting factors (NPF) that differentially control the Arp2/3 complex. In Drosophila, three different family members, SCAR (also known as WAVE), WASP and WASH (also known as CG13176), have been analyzed so far. Here, we characterized WHAMY, the fourth Drosophila WASP family member. whamy originated from a wasp gene duplication and underwent a sub-neofunctionalization. Unlike WASP, we found that WHAMY specifically interacted with activated Rac1 through its two CRIB domains, which were sufficient for targeting WHAMY to lamellipodial and filopodial tips. Biochemical analyses showed that WHAMY promoted exceptionally fast actin filament elongation, although it did not activate the Arp2/3 complex. Loss- and gain-of-function studies revealed an important function of WHAMY in membrane protrusions and cell migration in macrophages. Genetic data further implied synergistic functions between WHAMY and WASP during morphogenesis. Double mutants were late-embryonic lethal and showed severe defects in myoblast fusion. Trans-heterozygous mutant animals showed strongly increased defects in sensory cell fate specification. Thus, WHAMY is a novel actin polymerase with an initial partitioning of ancestral WASP functions in development and subsequent acquisition of a new function in cell motility during evolution. PMID- 26675240 TI - Hairpin DNA-Templated Silver Nanoclusters as Novel Beacons in Strand Displacement Amplification for MicroRNA Detection. AB - MicroRNA (miRNA) biomarkers display great potential for cancer diagnosis and prognosis. The development of rapid and specific methods for miRNA detection has become a hotspot. Herein, hairpin DNA-templated silver nanoclusters (AgNCs/HpDNA) were prepared and integrated into strand-displacement amplification (SDA) as a novel beacon for miRNA detection. The light-up platform was established based on guanine (G)-rich fluorescence enhancement that essentially converted the excitation/emission pair of AgNCs/HpDNAs from a shorter wavelength to a longer wavelength, and then achieved fluorescent enhancement at longer wavelength. On the basis of the validation of the method, the single and duplex detection were conducted in two plasma biomarkers (miR-16-5p and miR-19b-3p) for the diagnosis of gastric cancer. The probe (AgNCs/RED 16(7s)C) utilized for miR-16-5p detection adopted a better conformation with high specificity to recognize single-base mismatches by producing dramatically opposite signals (increase or decrease at 580 nm ex/640 nm em) while the probe (AgNCs/GRE 19b(5s)C) for miR-19b-3p generated dual signals (increase at 490 nm ex/570 nm em and decrease at 430 nm ex/530 nm em) with bright fluorescence in one reaction during the amplification, but unexpectedly was partially digested. This is for the first time to allow the generation of enhanced fluorescent AgNCs and the target recognition integrated into a single process, which offers great opportunity for specific miRNA detection in an easy and rapid way. PMID- 26675241 TI - Pre-existing, incidental and hemorrhagic AVMs in pregnancy and postpartum: Gestational age, morbidity and mortality, management and risk to the fetus. AB - OBJECTIVE: The objective of this article is to analyze the maternal and fetal outcomes of pregnancies that present with arteriovenous malformations (AVMs). METHODS: A literature review was performed that analyzed 65 cases of AVM during pregnancy previously reported in English literature. RESULTS: Sixty-five cases of pregnancy-associated AVM were identified. The patients' ages ranged from 16 to 45 years, with a mean of 28 +/- 4.9 years. Sixteen cases (24.6%) were pre-existing AVMs. There were 54 cases (83.1%) of AVM ruptured during pregnancy and postpartum: Six cases (11.1%) were in the first trimester, 24 (44.4%) were in the second, 22 (40.7%) were in the third trimester and two (3.7%) were postpartum. Unfavorable maternal clinical outcome (modified Rankin Scale (mRS) >= 2) was identified in 20 cases (30.8%) and abortion occurred in 10 cases (15.4%). There were three maternal deaths, yielding a case mortality rate of 4.6%. Fifty-three fetuses were born via cesarean section in 42 cases and vaginal delivery in 10 cases; 48 were in good health, three were temporarily intubated, one was macrosomic and one died. In univariate analysis, AVM hemorrhage presentation was significantly associated with a poor maternal outcome (mRS >= 2) (p = 0.030); however, not significantly associated with fetus risk (p = 0.864). Gestational age was not significantly associated with poor maternal outcome (p = 0.875) or fetal risk (p = 0.790). CONCLUSION: AVM hemorrhage presentation was significantly associated with poor maternal outcome. Pre-existing ruptured AVM may not be associated with fetal risk. Gestational age of AVM rupture was not significantly associated with poor maternal outcome or fetal risk. PMID- 26675242 TI - Low Leakage-Current InAsSb Nanowire Photodetectors on Silicon. AB - Axially doped p-i-n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density around 2 mA/cm(2) and a 20% cutoff of 2.3 MUm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III-V semiconductors with silicon technology. PMID- 26675244 TI - Assessment of the utility of ultrasonography with high-frequency transducers in the diagnosis of postoperative neuropathies. PMID- 26675245 TI - Holistic Health Care for the Medically Uninsured: The Church Health Center of Memphis. AB - The Church Health Center (CHC) in Memphis was founded in 1987 to provide quality, affordable health care for working, uninsured people and their families. With numerous, dedicated financial supporters and health care volunteers, CHC has become the largest faith-based health care organization of its type nationally, serving >61,000 patients. CHC embraces a holistic approach to health by promoting wellness in every dimension of life. It offers on-site services including medical care, dentistry, optometry, counseling, social work, and nutrition and fitness education, to promote wellness in every dimension of life. A 2012 economic analysis estimated that a $1 contribution to the CHC provided roughly $8 in health services. The CHC has trained >1200 Congregational Health Promoters to be health leaders and is conducting research on the effectiveness of faith community nurses partnering with congregations to assist in home care for patients recently discharged from Memphis hospitals. The MEMPHIS Plan, CHC's employer-sponsored health care plan for small business and the self-employed, offers uninsured people in lower-wage jobs access to quality, affordable health care. The CHC also conducts replications workshops several times a year to share their model with leaders in other communities. The Institute for Healthcare Improvement (IHI) recently completed a case study that concluded: "The CHC is one of a very few organizations successfully embodying all three components of the IHI Triple Aim by improving population health outcomes, enhancing the individual's health care experience, and controlling costs. All three have been part of the Center's DNA since its inception, and as a transforming force in the community, the model is well worth national attention." PMID- 26675243 TI - Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine. AB - Cocaine addiction continues to be a significant public health problem for which there are currently no effective FDA-approved treatments. Thus, there is a clear need to identify and develop novel pharmacotherapies for cocaine addiction. Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors in the ventral tegmental area (VTA) reduces intake of highly palatable food. As the neural circuits and neurobiological mechanisms underlying drug taking overlap to some degree with those regulating food intake, these findings suggest that activation of central GLP-1 receptors may also attenuate cocaine taking. Here, we show that intra-VTA administration of the GLP-1 receptor agonist exendin-4 (0.05 MUg) significantly reduced cocaine, but not sucrose, self administration in rats. We also demonstrate that cocaine taking is associated with elevated plasma corticosterone levels and that systemic infusion of cocaine activates GLP-1-expressing neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus that projects monosynaptically to the VTA. To determine the potential mechanisms by which cocaine activates NTS GLP-1-expressing neurons, we microinjected corticosterone (0.5 MUg) directly into the hindbrain fourth ventricle. Intraventricular corticosterone attenuated cocaine self-administration and this effect was blocked in animals pretreated with the GLP-1 receptor antagonist exendin-(9-39) (10 MUg) in the VTA. Finally, AAV-shRNA-mediated knockdown of VTA GLP-1 receptors was sufficient to augment cocaine self administration. Taken together, these findings indicate that increased activation of NTS GLP-1-expressing neurons by corticosterone may represent a homeostatic response to cocaine taking, thereby reducing the reinforcing efficacy of cocaine. Therefore, central GLP-1 receptors may represent a novel target for cocaine addiction pharmacotherapies. PMID- 26675246 TI - Resistance to dual-gene Bt maize in Spodoptera frugiperda: selection, inheritance, and cross-resistance to other transgenic events. AB - Transgenic crop "pyramids" producing two or more Bacillus thuringiensis (Bt) toxins active against the same pest are used to delay evolution of resistance in insect pest populations. Laboratory and greenhouse experiments were performed with fall armyworm, Spodoptera frugiperda, to characterize resistance to Bt maize producing Cry1A.105 and Cry2Ab and test some assumptions of the "pyramid" resistance management strategy. Selection of a field-derived strain of S. frugiperda already resistant to Cry1F maize with Cry1A.105 + Cry2Ab maize for ten generations produced resistance that allowed the larvae to colonize and complete the life cycle on these Bt maize plants. Greenhouse experiments revealed that the resistance was completely recessive (Dx = 0), incomplete, autosomal, and without maternal effects or cross-resistance to the Vip3Aa20 toxin produced in other Bt maize events. This profile of resistance supports some of the assumptions of the pyramid strategy for resistance management. However, laboratory experiments with purified Bt toxin and plant leaf tissue showed that resistance to Cry1A.105 + Cry2Ab2 maize further increased resistance to Cry1Fa, which indicates that populations of fall armyworm have high potential for developing resistance to some currently available pyramided maize used against this pest, especially where resistance to Cry1Fa was reported in the field. PMID- 26675248 TI - Facile Preparation and Ultrastable Performance of Single-Component White-Light Emitting Phosphor-in-Glass used for High-Power Warm White LEDs. AB - Long lifetime, excellent chromatic stability, and easily obtainable white light are becoming three outstanding challenges faced by the state-of-the-art high power white LEDs. This study explored a novel single-component white-light emitting phosphor-in-glass (PiG) for the first time. It has a quantum efficiency of 26.2% and exhibits excellent heat-resistance and good humidity-resistance characteristics which are rarely reported in traditional phosphor slurry. A proof of-concept warm white LEDs was fabricated by combining PiG with near-ultraviolet chip-on-board (n-UV COB). This method reported in this letter will open a new and simple approach to obtain excellent performance single-component luminescent convertor for advanced high-power white LEDs. PMID- 26675249 TI - The Experience of Childhood Trauma and Its Influence on the Course of Illness in First-Episode Psychosis: A Qualitative Study. AB - Persons with schizophrenia spectrum disorders often report high levels of childhood trauma, which often exacerbates symptoms and impede the process of recovery. However, little is known about how these traumas are experienced by service users and how they are integrated in their life stories. To examine this, we conducted in-depth interviews with 15 service users with a diagnosis of a first-episode nonaffective psychosis who had reported 1 or more childhood traumas in self-report measures. There was an unexpected discrepancy between the number of traumas reported in self-report measures and in semistructured interviews, and many of the traumas did not seem integrated in their personal narratives. The analyses further revealed that although participants often described complicated and traumatic childhood environments, they still felt supported by their families; they reported a range of ways in which they tried to cope with and gain control of their psychotic disorder, and they described a general optimistic view of the future. PMID- 26675247 TI - Craigslist versus print newspaper advertising for recruiting research participants for alcohol studies: Cost and participant characteristics. AB - INTRODUCTION: Technology has transformed our lifestyles in dramatic and significant ways, including new and less expensive options for recruiting study participants. This study examines cost and participant differences between two recruitment sources, Craigslist (CL), and print newspapers (PNs). This paper also reviewed and compared studies involving clinical trials published since 2010 that recruited participants using CL alone or in combination with other methods. METHOD: Secondary data analyses from a parent study involving a randomized controlled trial of a mail-based intervention to promote self-change with problem drinkers. RESULTS: Significant differences were found between CL and PN participants on most demographic and pretreatment drinking variables. While all participants had AUDIT scores suggestive of an alcohol problem and reported drinking at high-risk levels, CL participants had less severe drinking problem histories, were considerably younger, and had a higher socioeconomic status than PN participants. The total advertising costs for the 65 CL ads ($275) were significantly less than the 69 PN ads ($33, 311). The recruiting cost per eligible participant was vastly less expensive using CL ($1.46) compared to print newspaper ads ($116.88). CONCLUSIONS: Using CL is a viable recruitment method for soliciting participants, particularly those that are younger, for alcohol intervention studies. It is also less expensive than newspaper ads. When CL participants were recruited, they reported being slightly more confident to change their drinking than PN participants. Limitations of using CL are discussed, including that some initial ad responders gave inconsistent answers to similar questions and a few tried to enter the study more than once. PMID- 26675250 TI - Elevated Transglutaminase Activity Triggers Angiotensin Receptor Activating Autoantibody Production and Pathophysiology of Preeclampsia. AB - BACKGROUND: Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy associated with autoantibodies, termed AT1-AA, that activate the AT1 angiotensin receptor. Although the pathogenic nature of these autoantibodies has been extensively studied, little is known about the molecular cause of their generation. METHODS AND RESULTS: Here we show that tissue transglutaminase (TG2), an enzyme that conducts posttranslational modification of target proteins, directly modified the 7-amino acid (7-aa) epitope peptide that localizes to the second extracellular loop of the AT1 receptor. These findings led us to further discover that plasma transglutaminase activity was induced and contributed to the production of AT1-AA and disease development in an experimental model of PE induced by injection of LIGHT, a tumor necrosis factor superfamily member. Key features of PE were regenerated by adoptive transfer of purified IgG from LIGHT injected pregnant mice and blocked by the 7-amino acid epitope peptide. Translating our mouse research to humans, we found that plasma transglutaminase activity was significantly elevated in PE patients and was positively correlated with AT1-AA levels and PE features. CONCLUSIONS: Overall, we provide compelling mouse and human evidence that elevated transglutaminase underlies AT1-AA production in PE and highlight novel pathogenic biomarkers and innovative therapeutic possibilities for the disease. PMID- 26675251 TI - Relation Between Circulating Inflammatory Chemokines and Vascular Characteristics in Healthy, Young Children. AB - BACKGROUND: Atherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators of vascular inflammation. However, this has not extensively been investigated. Therefore, we studied in healthy young children whether chemokines monocyte chemotactic protein 1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and vascular and intercellular adhesion molecules (VCAM and ICAM) related to vascular characteristics of the carotid artery. METHODS AND RESULTS: We obtained demography, anthropometry, and overnight fasting plasma of 139 eight-year-old children of the Wheezing Illnesses Study Leidsche Rijn birth cohort. Carotid intima-media thickness (CIMT), distensibility, and Young's Elastic Modulus (YEM) of the common carotid artery were measured sonographically. Chemokine plasma levels were assessed using a multiplex assay. We studied the relation between the chemokines and vascular characteristics using multivariable linear regression analyses with adjustments for sex, systolic blood pressure, homeostasis model assessment of insulin resistance, triglycerides, low-density lipoprotein- and high-density lipoprotein cholesterol. Of the studied chemokines, RANTES related to common carotid distensibility and YEM. One standard deviation increase in RANTES level related to a 5.45-MPA(-1) (95% confidence interval [CI], -9.43, -1.39; P=0.01) decrease in distensibility and to a 5.55-kPa increase in YEM (95% CI, 0.40, 10.85; P=0.03). RANTES did not relate to CIMT. MCP-1, VCAM, and ICAM did not relate to any of the studied vascular characteristics. CONCLUSION: RANTES appears to be involved in the development of preatherosclerotic inflammatory vascular alterations already in healthy, young children. This may provide further insight into the early-life origins of atherosclerosis. PMID- 26675252 TI - QT Adaptation and Intrinsic QT Variability in Congenital Long QT Syndrome. AB - BACKGROUND: Increased variability of QT interval (QTV) has been linked to arrhythmias in animal experiments and multiple clinical situations. Congenital long QT syndrome (LQTS), a pure repolarization disease, may provide important information on the relationship between delayed repolarization and QTV. METHODS AND RESULTS: Twenty-four-hour Holter monitor tracings from 78 genotyped congenital LQTS patients (52 females; 51 LQT1, 23 LQT2, 2 LQT5, 2 JLN, 27 symptomatic; age, 35.2+/-12.3 years) were evaluated with computer-assisted annotation of RR and QT intervals. Several models of RR-QT relationship were tested in all patients. A model assuming exponential decrease of past RR interval contributions to QT duration with 60-second time constant provided the best data fit. This model was used to calculate QTc and residual "intrinsic" QTV, which cannot be explained by heart rate change. The intrinsic QTV was higher in patients with long QTc (r=0.68; P<10(-4)), and in LQT2 than in LQT1/5 patients (5.65+/-1.28 vs 4.46+/-0.82; P<0.0002). Both QTc and intrinsic QTV were similar in symptomatic and asymptomatic patients (467+/-52 vs 459+/-53 ms and 5.10+/-1.19 vs 4.74+/-1.09, respectively). CONCLUSIONS: In LQTS patients, QT interval adaptation to heart rate changes occurs with time constant ~60 seconds, similar to results reported in control subjects. Intrinsic QTV correlates with the degree of repolarization delay and might reflect action potential instability observed in animal models of LQTS. PMID- 26675253 TI - Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification. AB - BACKGROUND: Ectopic vascular calcification is a common condition associated with aging, atherosclerosis, diabetes, and/or chronic kidney disease. Smooth muscle cells are the best characterized source of osteogenic progenitors in the vasculature; however, recent studies suggest that cells of endothelial origin can also promote calcification. To test this, we sought to increase the osteogenic potential of endothelial cells by overexpressing tissue-nonspecific alkaline phosphatase (TNAP), a key enzyme that regulates biomineralization, and to determine the pathophysiological effect of endothelial TNAP on vascular calcification and cardiovascular function. METHODS AND RESULTS: We demonstrated previously that mice transgenic for ALPL (gene encoding human TNAP) develop severe arterial medial calcification and reduced viability when TNAP is overexpressed in smooth muscle cells. In this study, we expressed the ALPL transgene in endothelial cells following endothelial-specific Tie2-Cre recombination. Mice with endothelial TNAP overexpression survived well into adulthood and displayed generalized arterial calcification. Genes associated with osteochondrogenesis (Runx2, Bglap, Spp1, Opg, and Col2a1) were upregulated in the aortas of endothelial TNAP animals compared with controls. Lesions in coronary arteries of endothelial TNAP mice showed immunoreactivity to Runx2, osteocalcin, osteopontin, and collagen II as well as increased deposition of sialoproteins revealed by lectin staining. By 23 weeks of age, endothelial TNAP mice developed elevated blood pressure and compensatory left ventricular hypertrophy with preserved ejection fraction. CONCLUSIONS: This study presented a novel genetic model demonstrating the osteogenic potential of TNAP-positive endothelial cells in promoting pathophysiological vascular calcification. PMID- 26675254 TI - Left Atrial Inexcitability in Children With Congenital Lupus-Induced Complete Atrioventricular Block. AB - BACKGROUND: Congenital atrioventricular block is a well-established immunologic complication of maternal systemic lupus erythematosus. We sought to further characterize the electrophysiological manifestations of maternal systemic lupus erythematosus on neonatal atria. METHODS AND RESULTS: Cases of isolated congenital atrioventricular block treated at our center over the past 41 years were identified. Data were extracted from clinical charts, pacemaker interrogations, ECGs, echocardiograms, and histopathological reports, when available. Of 31 patients with isolated congenital atrioventricular block, 18 were negative for maternal antibodies and had normal epicardial atrial sensing and pacing thresholds. In contrast, 12 of 13 patients with positive maternal antibodies had epicardial pacemakers, 5 (42%) of whom had left atrial (LA) inexcitability and/or atrial conduction delay. In 3 patients, the LA could not be captured despite high-output pacing. The fourth patient had acutely successful LA appendage and left ventricular lead placement. At early follow-up, an increased delay between the surface P-wave and intracardiac atrial depolarization was observed, indicative of atrial conduction delay. The fifth patient exhibited LA lead dysfunction, with atrial under-sensing and an increased capture threshold, 2 weeks after implantation. Biopsies of LA appendages performed in 2 patients showed no evidence of atrial fibrosis or loss of atrial myocytes. CONCLUSIONS: Herein, we report previously undescribed yet prevalent electrophysiological ramifications of maternal systemic lupus erythematosus, which extend beyond congenital atrioventricular block to encompass alterations in LA conduction, including LA inexcitability. These manifestations can complicate epicardial pacemaker implantation in newborns. In the absence of histological evidence of extensive atrial fibrosis, immune-mediated functional impairment of electrical activity is suspected. PMID- 26675257 TI - Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche. AB - The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets. PMID- 26675256 TI - Autophagy induction causes a synthetic lethal sensitization to ribonucleotide reductase inhibition in breast cancer cells. AB - Macroautophagy can promote cellular survival or death depending on the cellular context and its extent. We hypothesized that autophagy induction would synergize with a therapeutic agent targeting the autophagic cargo. To test this hypothesis, we treated breast cancer MDA-MB-231 cells with tamoxifen (TMX), which induces autophagy through an estrogen receptor-independent pathway. Induction of autophagy reduced cellular levels of RRM2, a subunit of ribonucleotide reductase (RR), the rate limiting enzyme in the production of deoxyribonucleotide triphosphates (dNTPs). This autophagy inducer was combined with COH29, an inhibitor developed in our laboratory that targets RR through a novel mechanism. The combination therapy showed synergistic effects on cytotoxicity in vitro and in an in vivo xenograft model. This cytotoxicity was blocked by knockdown of the autophagy protein ATG5 or addition of chloroquine, an autophagy inhibitor. The combined therapy also induced dNTP depletion and massive genomic instability, leading us to hypothesize that combining autophagy induction with RR inhibition can lead to mitotic catastrophe in rapidly dividing cells. We propose that this TMX + COH29 combined therapy may have clinical benefit. Furthermore, autophagy induction may be a general mechanism for augmenting the effects of chemotherapeutic agents. PMID- 26675258 TI - miR-30a inhibits endothelin A receptor and chemoresistance in ovarian carcinoma. AB - Drug resistance remains the major clinical barrier to successful treatment in epithelial ovarian carcinoma (EOC) patients, and the evidence of microRNA involvement in drug resistance has been recently emerging. Endothelin-1 (ET 1)/ETA receptor (ETAR) axis is aberrantly activated in chemoresistant EOC cells and elicits pleiotropic effects promoting epithelial-to-mesenchymal transition (EMT) and the acquisition of chemoresistance. However, the relationship between ETAR and miRNA is still unknown. Hence, in this study we evaluated whether dysregulation of miRNA might enhance ETAR expression in sensitive and resistant EOC cells. Based on bioinformatic tools, we selected putative miRNA able to recognize the 3'UTR of ETAR. An inverse correlation was observed between the expression levels of miR-30a and ETAR in both EOC cell lines and tumor samples. miR-30a was found to specifically bind to the 3'UTR of ETAR mRNA, indicating that ETAR is a direct target of miR-30a. Overexpression of miR-30a decreased Akt and mitogen activated protein kinase signaling pathway activation, cell proliferation, invasion, plasticity, EMT marker levels, and vascular endothelial growth factor release. Interestingly, ectopic expression of miR-30a re-sensitized platinum-resistant EOC cells to cisplatinum-induced apoptosis. Consistently, resistant EOC xenografts overexpressing miR-30a resulted in significantly less tumor growth than controls. Together our study provides a new perspective on the regulatory mechanism of ETAR gene. Interestingly, our findings highlight that blockade of ETAR regulatory axis is the mechanism underlying the tumor suppressor function of miR-30a in chemoresistant EOC cells. PMID- 26675259 TI - Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. AB - Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10-18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma. PMID- 26675262 TI - Factors That Control C-C Cleavage versus C-H Bond Hydroxylation in Copper Catalyzed Oxidations of Ketones with O2. AB - The Cu-catalyzed oxidation of ketones with O2 has recently been extensively utilized to cleave the alpha-C-C bond. This report examines the selective aerobic hydroxylation of tertiary alpha-C-H bonds in ketones without C-C cleavage. We set out to understand the underlying mechanisms of these two possible reactivity modes. Using experimental, in situ IR spectroscopic, and computational studies, we investigated several mechanisms. Our data suggest that both C-C cleavage and C H hydroxylation pathways proceed via a common key intermediate, i.e., an alpha peroxo ketone. The fate of this peroxide dictates the ultimate product selectivity. Specifically, we uncovered the role of hppH [=1,3,4,6,7,8-hexahydro 2H-pyrimido[1,2-a]pyrimidine] to act not only as a base in the transformation but also as a reductant of the peroxide to the corresponding alpha-hydroxy ketone. This reduction may also be accomplished through exogenous phosphine additives, therefore allowing the tuning of reduction efficiency toward higher driving forces, if required (e.g., for more-activated substrates). The likely competitive pathway is the cleavage of peroxide to the alpha-oxy radical (likely catalyzed by Cu), which is computationally predicted to spontaneously trigger C-C bond cleavage. Increasing the susceptibility of this deperoxidation step via (i) the removal of reductant (use of different base, e.g., DBU) or the modulation of (ii) the substitution pattern toward greater activation (substrate control) and (iii) the nature of Cu catalyst (counterion and solvent dependence) will favor the C-C cleavage product. PMID- 26675260 TI - Epigenetic modification of TLR4 promotes activation of NF-kappaB by regulating methyl-CpG-binding domain protein 2 and Sp1 in gastric cancer. AB - Toll-like receptor 4 (TLR4) is important in promoting the immune response in various cancers. Recently, TLR4 is highly expressed in a stage-dependent manner in gastric cancer, but the regulatory mechanism of TLR4 expression has been not elucidated it. Here, we investigated the mechanism underlying regulation of TLR4 expression through promoter methylation and histone modification between transcriptional regulation and silencing of the TLR4 gene in gastric cancer cells. Chromatin immunoprecipitation was carried out to screen for factors related to TLR4 methylation such as MeCP2, HDAC1, and Sp1 on the TLR4 promoter. Moreover, DNA methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-dC) induced demethylation of the TLR4 promoter and increased H3K4 trimethylation and Sp1 binding to reactivate silenced TLR4. In contrast, although the silence of TLR4 activated H3K9 trimethylation and MeCP2 complex, combined treatment with TLR4 agonist and 5-aza-dC upregulated H3K4 trimethylation and activated with transcription factors as Sp1 and NF-kappaB. This study demonstrates that recruitment of the MeCP2/HDAC1 repressor complex increases the low levels of TLR4 expression through epigenetic modification of DNA and histones on the TLR4 promoter, but Sp1 activates TLR4 high expression by hypomethylation and NF-kappaB signaling in gastric cancer cells. PMID- 26675261 TI - Mps1 is SUMO-modified during the cell cycle. AB - Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis. PMID- 26675263 TI - Sedentary Behavior in the Workplace: A Potential Occupational Hazard for Radiologists. AB - In this study, we sought to quantify the sedentary worklife of the radiologist, a potential health risk. Radiologists of all training levels at our academic institution were surveyed to estimate the levels of at-work and out-of-work sitting. Fitbit One activity monitors were used to measure the at-work activity levels of radiology, pediatric, and internal medicine (IM) residents. Correlation between awareness and utilization of dynamic (sitting or standing, walking, or biking) picture archiving and communication system (PACS) workstations among radiology residents was assessed. Among surveyed radiologists (n = 89), 78% estimated sitting for at least 6 hours per workday. Estimated workplace sitting accounted for most of the total sitting for 81% of respondents. As measured by activity monitors, radiology residents (n = 27) took fewer steps per day (2683 vs 4602 vs 4967) and per hour (294 vs 419 vs 444) and experienced more sedentary time per hour (40.3 vs 36.2 vs 34.9min/h) than IM (n = 15) and pediatric (n = 9) residents. Activity experienced during reading room-based work and interventional work was compared by studying 4 additional radiology residents during both types of rotations. Reading-room activity was low, whereas activity on interventional rotations surpassed average levels for the pediatric and IM residents in our study. Radiology residents' (n = 28) awareness and utilization of dynamic PACS workstations varied among reading rooms, but were generally low-75% reported never or rarely using them. Resident utilization correlated with awareness of dynamic workstations available at our institution (R(2) = 0.64; P = 0.013). In conclusion, radiology residents in our study led more sedentary worklives compared with residents from other specialties and took minimal advantage of available tools to mitigate this. Potential health risks of inactivity justify individual and departmental efforts to limit workplace inactivity among radiologists. PMID- 26675264 TI - ORNL workshop on Biomembranes. PMID- 26675265 TI - Ultrasound quiz. PMID- 26675266 TI - Opinion: How to manage subepithelial lesions of the upper gastrointestinal tract? AB - Subepithelial lesions (SELs) in the upper gastrointestinal (GI) tract are relatively frequent findings in patients undergoing an upper GI endoscopy. These tumors, which are located below the epithelium and out of reach of conventional biopsy forceps, may pose a diagnostic challenge for the gastroenterologist, especially when SELs are indeterminate after endoscopy and endoscopic ultrasound (EUS). The decision to proceed with further investigation should take into consideration the size, location in the GI tract, and EUS features of SELs. Gastrointestinal stromal tumor (GIST) is an example of an SEL that has a well recognized malignant potential. Unfortunately, EUS is not able to absolutely differentiate GISTs from other benign hypoechoic lesions from the fourth layer, such as leiomyomas. Therefore, EUS-guided fine needle aspiration (EUS-FNA) is an important tool for correct diagnosis of SELs. However, small lesions (size < 2 cm) have a poor diagnostic yield with EUS-FNA. Moreover, studies with EUS-core biopsy needles did not report higher rates of histologic and diagnostic yields when compared with EUS-FNA. The limited diagnostic yield of EUS-FNA and EUS-core biopsies of SELs has led to the development of more invasive endoscopic techniques for tissue acquisition. There are initial studies showing good results for tissue biopsy or resection of SELs with endoscopic submucosal dissection, suck-ligate-unroof-biopsy, and submucosal tunneling endoscopic resection. PMID- 26675267 TI - Erratum. PMID- 26675268 TI - Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes. AB - Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM. MATERIAL AND METHODS: A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were collected using standard methods to assess the effect of age on the clinical and biochemical phenotype of patients with T2DM. RESULTS: We have noted that patients with T2DM > 70 years old have a clinical and biochemical phenotype different from younger subjects (<60 years) including longer times since diabetes onset, higher diastolic blood pressure levels, and lower body mass index (BMI) values. As regards to biological variables, these patients have lower triglyceride levels, impaired kidney function, and lower HbA1c values. Prevalence of metabolic syndrome is lower in patients with T2DM > 70 years of age. Age was inversely related to parameters associated to metabolic syndrome (BMI, waist circumference, blood pressure, and triglyceride levels). CONCLUSIONS: We have defined the clinical and biochemical profile of patients with T2DM > 70 years attending health care centers. In addition, the prevalence of stroke, kidney disease, and distal symmetrical polyneuropathy is higher in patients with T2DM >70 years as compared to younger patients (<60 years). PMID- 26675269 TI - Modeling Protein Loop Structure by Cyclic Coordinate Descent-based Approach. AB - In both predicting protein loop structure and flexible areas in a docking interface, modeling local loop conformation plays a vital role. We address the challenge with a topological manipulation method based on the cyclic coordinate descent (CCD) algorithm. The protein loop conformation sampler (LMbCCD2) presented here allows us to move some key points of the loop toward some specific positions. We test the method's performance on sets of loops, and the results show that LMbCCD2 accurately controls the loop's topology. At last we use LMbCCD2 on flexible protein-peptide docking, and it shows that LMbCCD2 can improve the accuracy of flexible peptide folding and the full docking result. PMID- 26675280 TI - Treating Colon Cancer Cells with FK228 Reveals a Link between Histone Lysine Acetylation and Extensive Changes in the Cellular Proteome. AB - The therapeutic value of FK228 as a cancer treatment option is well known, and various types of cancer have been shown to respond to this drug. However, the complete mechanism of FK228 and the affect it has on histone lysine acetylation and the colon cancer cell proteome are largely unknown. In the present study, we used stable isotope labeling by amino acids in cell culture (SILAC) and affinity enrichment followed by high-resolution liquid chromatograph-mass spectrometer (LC MS)/MS analysis to quantitate the changes in the lysine acetylome in HCT-8 cells after FK228 treatment. A total of 1,194 lysine acetylation sites in 751 proteins were quantified, with 115 of the sites in 85 proteins being significantly upregulated and 38 of the sites in 32 proteins being significantly downregulated in response to FK228 treatment. Interestingly, 47 histone lysine acetylation sites were identified in the core histone proteins. We also found a novel lysine acetylation site on H2BK121. These significantly altered proteins are involved in multiple biological functions as well as a myriad of metabolic and enzyme regulated pathways. Taken together, the link between FK228 function and the downstream changes in the HCT-8 cell proteome observed in response to FK228 treatment is established. PMID- 26675281 TI - Clinical performance of a novel ultrathin strut, low-dose, sirolimus-eluting stent with abluminal-only biodegradable polymeric coating for patients undergoing percutaneous coronary intervention in the daily practice. AB - BACKGROUND: The present study aimed to evaluate the clinical performance, in the daily practice of a busy catheterization laboratory, of a novel drug-eluting stent (DES) built with an ultra-thin-strut metallic platform, eluting sirolimus at low doses, abluminal coated with biodegradable polymers, and mounted in a low compliant delivery system. METHODS: Prospective, single-arm study, comprising all consecutive patients undergoing percutaneous coronary intervention (PCI) with the InspironTM sirolimus-eluting stent (SES) (Scitech, Aparecida de Goiania, Brazil). The primary endpoint was the occurrence of major adverse cardiac events (MACE) [cardiac death, non-PCI related myocardial infarction (MI), or target vessel revascularization (TVR)]. RESULTS: A total of 470 patients were included, from which 51.3% were diabetics, 33.8% had triple-vessel disease, 15.3% had heart failure, 38.9% had at least one bifurcation treated, 19.8% were treated for a bare metal stent restenosis, and 61.9% had at least one type C lesion; one or more of these features were found in 96.0%. At 300 days, the rate target lesion revascularization was 5.4% and the rate of MACE was 8.1%. The incidence of definite or probable stent thrombosis was 0.4%, with no cases between 30 and 300 days. CONCLUSIONS: The novel stent is associated with excellent short and mid term clinical outcomes in patients treated with PCI in the daily practice. PMID- 26675282 TI - Tissue miR-193b as a Novel Biomarker for Patients with Ovarian Cancer. AB - BACKGROUND MiRNAs play important roles in regulating many fundamental biological processes. Deregulation of miRNAs is involved in the initiation and progression of cancer. MiR-193b is regarded as tumor suppressor in many types of cancers. However, the role of miR-193b in ovarian cancer is poorly understood. MATERIAL AND METHODS The expression level of miR-193b in ovarian cancer cell lines and ovarian cancer samples was evaluated using quantitative real-time reverse transcription-PCR (qRT-PCR). The ovarian cancer patients were categorized into a high miR-193b expression group and a low miR-193b expression group according to the median miR-193b expression level. The correlation between tissue miR-193b expression and the patients' clinicopathological factors, as well as survival, was also analyzed. RESULTS The results showed that the miR-193b expression was significantly down-regulated in ovarian cancer cell lines and tumor tissues compared with normal controls. In addition, tissue miR-193b expression was positively correlated with FIGO stage (P=0.001), histological grade (P=0.032), ascites (P=0.019), lymph node metastasis (P=0.003), and tumor size (P=0.041). Among 116 patients with ovarian cancer examined, the 5-year overall survival (OS) rates were 62.5% and 22.01% in patients with high and low miR-193b expression, respectively (P=0.003). Multivariate analysis showed that tissue miR-193b is an independent prognostic factor in patients with ovarian cancer (HR=4.219; P=0.015). CONCLUSIONS Reduction of miR-193b was found in ovarian cancer and its lower expression was associated with poorer prognosis. Tissue miR-193b showed potential as novel biomarker for ovarian cancer. PMID- 26675283 TI - Long-term patterns of relapse and survival following definitive intensity modulated radiotherapy for non-endemic nasopharyngeal carcinoma. AB - BACKGROUND: We report treatment outcomes for a large non-endemic cohort of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. METHODS: We identified 177 consecutive patients with newly diagnosed, non-metastatic nasopharyngeal cancer treated with definitive IMRT between 1998 and 2011. Endpoints included local, regional, distant control, and overall survival. RESULTS: Median follow-up was 52months. The 3-/5-year actuarial rates of local control, regional control, distant control, and overall survival were 92%/83%, 93%/91%, 86%/83%, and 87%/74%, respectively. The median time to local recurrence was 30months; the annual hazard of local recurrence did not diminish until the 6th year of follow-up. CONCLUSIONS: Overall, we observed excellent rates of disease control and survival consistent with initially reported results from our institution. Attaining locoregional control in patients with extensive primary tumors remains a significant clinical challenge. With mature follow-up we observed that more than half of observed local relapses occurred after 2years, a pattern distinct from that of carcinomas arising from other head and neck sites. These findings raise the possibility that patients with NPC may benefit from close follow-up during post-treatment years 3-5. PMID- 26675284 TI - MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder. AB - OBJECTIVES: MicroRNAs (miRNAs, miRs) have shown diagnostic and prognostic potential for oral cancer but their role in oral potentially malignant disorder (OPMD) has been less investigated. We aimed to assess whether miR-21 and miR-31, two of the most relevant miRNAs in oral cancer, are useful as prognostic factors for OPMD progression. MATERIALS AND METHODS: miR-21 and miR-31 in 20 saliva samples and 46 tissue samples from patients with OPMD (mean follow-up of 820days) were analyzed by quantitative reverse transcription PCR and in situ hybridization, respectively. The log-rank test, receiver operating characteristic curve, and Kaplan-Meier disease free survival analysis were used to assess the correlation between miRNA levels and OPMD progression. RESULTS: Significantly increased salivary miR-21 and miR-31 expression (P=0.003 and P<0.001, respectively) was observed in patients with OPMD compared to control individuals. Patients with recurrent OPMD and/or malignant transformation exhibited a further augmented expression of miR-31, but not miR-21, in the epithelium. Furthermore, increased miR-31 expression as well as epithelial dysplasia is an independent risk factor for OPMD progression as demonstrated in Cox-proportional hazard model (HR: 8.43, P<0.05, 95%CI: 1.04 to 68.03). CONCLUSIONS: Salivary miR-21 and miR-31 are applicable as useful OPMD screening tools. Epithelial dysplasia and miR-31 up regulation synergistically predict the increased incidence of recurrence and/or malignant transformation in patients with OPMD. Detection of miR-31 expression is an adjuvant method for screening of high-risk OPMD. PMID- 26675285 TI - Epidemiology of Frontotemporal Lobar Degeneration in Northern Finland. AB - BACKGROUND: Frontotemporal lobar degeneration (FTLD) is responsible for as many as every fifth case of early-onset dementia. Very few epidemiological studies of FTLD have been conducted; there are no published epidemiological data of FTLD from Finland or the other Nordic countries. The C9ORF72 expansion-associated FTLD is common in Finland; thus, the prevalence of FTLD is expected to be high in this population. METHODS: We retrospectively evaluated the incidence and prevalence of FTLD in university hospital settings in Northern Finland. RESULTS: The mean 1 year incidence of FTLD was 5.54/100,000 (range 1.9-11.3/100,000) in the population aged 45-65 years. The prevalence of FTLD in the same age group was 20.5/100,000. CONCLUSION: The incidence and prevalence of FTLD in Finland seem to be the highest in Europe. However, studies from different countries may not be directly mutually comparable due to methodological issues. PMID- 26675286 TI - Pre-Hypertension in Apparently Healthy Young Adults: Incidence and Influence of Haemoglobin Level. AB - INTRODUCTION: Prehypertension is a precursor of clinical hypertension and consequently of the cardiovascular disease. Recent studies have found positive correlation between Haemoglobin Level (Hb) and Blood Pressure (BP). But the presumed association between Hb and BP has not been investigated in healthy young adults. AIM: This study aimed to estimate the incidence of prehypertension and the influence of Hb level on BP in healthy young adults. MATERIALS AND METHODS: This was a cross-sectional study done in 84 apparently healthy undergraduate medical students aged between 18-23 years, of either sex. In study subjects, BP and haemoglobin content was measured. Prehypertension was defined as BP levels of 120 to 139/80 to 89 mm Hg. Statistical analysis was done by unpaired t-test and Pearson correlation Coefficient tests. RESULTS: Incidence of prehypertension was 50%. In 24% of the study subjects both systolic and diastolic BP was in prehypertensive state. In another 26% of study subjects only systolic BP was above normal. There was positive correlation between systolic BP and Hb level (p = 0.0015). CONCLUSION: High incidence of prehypertension especially systolic prehypertension prevails inapparently healthy medical undergraduate students. In them, positive correlation between Hb and systolic BP persists. PMID- 26675287 TI - Identifying low-coverage surface species on supported noble metal nanoparticle catalysts by DNP-NMR. AB - DNP-NMR spectroscopy has been applied to enhance the signal for organic molecules adsorbed on gamma-Al2O3-supported Pd nanoparticle catalysts. By offering >2500 fold time savings, the technique enabled the observation of (13)C-(13)C cross peaks for low coverage species, which were assigned to products from oxidative degradation of methionine adsorbed on the nanoparticle surface. PMID- 26675288 TI - The work of case managers as experienced by older persons (75+) with multi morbidity - a focused ethnography. AB - BACKGROUND: Complex health systems make it difficult for older persons (75+) with multi-morbidity to achieve continuity of care. Case management could be one way to address this difficulty. Currently, there is a need to extend the knowledge regarding case management as experienced by those utilising the services, namely older persons (75+) with multi-morbidity. The study aimed to explore older persons' (75+) with multi-morbidity experiences of case managers. METHODS: The study design was qualitative and used a focused ethnographic approach. Data was collected through individual interviews with 13 older persons and by participant observations with accompanying field notes, all conducted in 2012-2013. RESULTS: The data revealed four themes illustrating the older persons' experiences of case managers: 1) Someone providing me with a trusting relationship; 2) Someone assisting me; 3) Someone who is on my side; and 4) Someone I do not need at present. CONCLUSIONS: This study illustrates the importance of establishing trusting relationships between older persons and their case managers in order to truly provide assistance. The older persons valued the case managers acting as informed but unbiased facilitators. The findings could be of help in the development of case management interventions better designed for older persons with multi-morbidity. PMID- 26675289 TI - In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer. AB - BACKGROUND: We examined the anti-tumor effect and radiosensitizing potential of a small molecule inhibitor of fibroblast growth factor receptor (FGFR) in colorectal cancer (CRC) in vitro and in vivo. METHODS: Effects of in vitro drug treatment on cell survival, proliferation, FGFR signaling, cell cycle distribution, apoptosis and radiosensitivity were assessed using various CRC cell lines with FGFR wild type (Caco2 and HCA7) and FGFR2 amplification (HCT116, NCI H716). In vivo tumor responses to FGFR inhibition with and without radiation therapy were evaluated by growth delay assays in two colorectal xenograft mouse models (NMRI nu/nu mice injected with NCI-H716 or CaCo2 cells). Mechanistic studies were conducted using Western blot analysis, immunohistochemistry and qPCR. RESULTS: In the tested cell lines, the FGFR inhibitor (JNJ-42756493) was effective in vitro and in vivo in CRC tumors with highest expression of FGFR2 (NCI-H716). In vitro, cell proliferation in this line was decreased, associated with increased apoptotic death and decreased cell survival. In vivo, growth of NCI-H716 tumors was delayed by 5 days by drug treatment alone, although when drug delivery was stopped the relative tumor volume increased compared to control. The FGFR inhibitor did not radiosensitize NCI-H716 tumors either in vitro or in vivo. CONCLUSIONS: Among tested CRC cell lines, the growth inhibitory activity of this FGFR inhibitor was evident in cell lines with high constitutive FGFR2 expression, suggesting that FGFR addiction may provide a window for therapeutic intervention, though caution is advised. Preclinical study with NCI-H716 and Caco2 tumor demonstrated that continued presence of drug could be essential for tumor growth control, especially in cells with aberrant FGFR expression. In the tested set-up, the inhibitor showed no radiosensitizing effect. PMID- 26675291 TI - Fusion Between Maxillary Premolar and A Supernumerary Tooth: A Rare Case Presentation. PMID- 26675290 TI - Increased Frontal Response May Underlie Decreased Tinnitus Severity. AB - OBJECTIVES: The overall goal of the study was to identify functional and behavioral differences between individuals with higher tinnitus distress and individuals with lower tinnitus distress. Subsequent exploratory analyses were conducted to investigate the role physical activity may have on the observed results between high and low distress groups. The purpose of the experiment was to identify brain regions to be targeted in future intervention studies for tinnitus. DESIGN: A total of 32 individuals with varying levels of tinnitus severity were recruited from the Urbana-Champaign area. Volunteers were divided into higher tinnitus distress (HD) and lower tinnitus distress (LD) groups. Note that these groups also significantly differed based on physical activity level and were subsequently stratified into higher and lower physical activity level subgroups for exploratory analysis. While in a functional magnetic resonance imaging (fMRI) scanner, subjects listened to affective sounds classified as pleasant, neutral or unpleasant from the International Affective Digital Sounds database. RESULTS: The HD group recruited amygdala and parahippocampus to a greater extent than the LD group when listening to affective sounds. The LD group engaged frontal regions to a greater extent when listening to the affective stimuli compared to the HD group. Both higher physical activity level subgroups recruited more frontal regions, and both lower levels of physical activity subgroups recruited more limbic regions respectively. CONCLUSION: Individuals with lower tinnitus distress may utilize frontal regions to better control their emotional response to affective sounds. Our analysis also suggests physical activity may contribute to lower tinnitus severity and greater engagement of the frontal cortices. We suggest that future intervention studies focus on changes in the function of limbic and frontal regions when evaluating the efficacy of treatment. Additionally, we recommend further investigation concerning the impact of physical activity level on tinnitus distress. PMID- 26675293 TI - Oral Health Related Quality of Life in a Group of Geriatrics. AB - BACKGROUND: A good quality of life in elderly population is related to different aspects of health including oral health. The aim of this study was to determine oral health-related quality of life (OHR-QoL) in elderly patients referred for dental or oro-maxillo-facial complaints to Mashhad dental school (MDS) and compare them with a group of normal population. MATERIALS AND METHODS: A total of 99 patients from MDS (as case group) and 114 elderly people as control were enrolled in this cross-sectional study. Control group were chosen among the pilgrims who had come to the holy shrine of Imam Reza (Haram). Persian version of OIDP (Oral Impact of Daily Performance) index was used. Data were entered to SPSS 11.5 and Statistical analysis was performed. RESULTS: A total of 213 (case =99, control=114) cases were enrolled. Mean Performance score (MPS) was 6.27+/-10.47 (7.96+/-11.95 in case group, and 4.80+/-8.77 in control group) and the difference was significant (p=0.015). Age was conversely correlated with MPS (r=0.0125, p=0.24) although this correlation was not significant. We found, in oro maxillofacial functions, ill-fit dentures, oral ulcers, pain and tooth mobility were major determinants of OHR-QoL. Number of impaired functions was directly and significantly correlated with MPS (r=0.92, p<0.001). CONCLUSION: Some daily functions like speaking, emotional status, cleaning teeth, physical activity were impaired in case group. Oral and maxillofacial diseases were more prevalent in case group and can be an important impairing issue in OHR-QoL. PMID- 26675294 TI - The Changing Face of Hallucination Research: The International Consortium on Hallucination Research (ICHR) 2015 Meeting Report. AB - This article reports on the Third Biennial Meeting of the International Consortium on Hallucinations Research, held in Melbourne, Australia, in October 2015. Following a public conference in which research findings were considered in relation to subjective experience and practice, 9 multidisciplinary working groups examined key current issues in progressing the conceptualization and research of hallucinations. Work group topics included: multicenter validation of the transdiagnostic and multimodal Questionnaire for Psychotic Experiences; development of an improved outcome measure for psychological therapies; the relationship between inhibition and hallucinations across multiple levels of explanation; hallucinations in relation to sleep phenomena; emotion and hallucinations; multiple interactions between the experience of self and hallucinations; interactions between language, auditory and memory networks; resting state networks including the default mode; and analyses arising from functional magnetic resonance imaging (fMRI) data-sharing. Major themes in hallucinations research identified during the meeting included (1) progression beyond the auditory verbal modality in schizophrenia to consider hallucinations across modalities and different populations; (2) development of new measures; (3) the central role of multisite collaboration through shared data collection and data pooling; (4) study of time-based and interactive models of hallucination; and (5) the need to increase the accessibility and availability of "real-life" interventions for people with persisting and distressing hallucinations. PMID- 26675292 TI - A Systematic Review of the Cost-Effectiveness of Biologics for the Treatment of Inflammatory Bowel Diseases. AB - BACKGROUND: Biologics are used for the treatment of inflammatory bowel diseases, Crohn's disease and ulcerative colitis refractory to conventional treatment. In order to allocate healthcare spending efficiently, costly biologics for inflammatory bowel diseases are an important target for cost-effectiveness analyses. The aim of this study was to systemically review all published literature on the cost-effectiveness of biologics for inflammatory bowel diseases and to evaluate the methodological quality of cost-effectiveness analyses. METHODS: A literature search was performed using Medline (Ovid), Cochrane Library, and SCOPUS. All cost-utility analyses comparing biologics with conventional medical treatment, another biologic treatment, placebo, or surgery for the treatment of inflammatory bowel diseases in adults were included in this review. All costs were converted to the 2014 euro. The methodological quality of the included studies was assessed by Drummond's, Philips', and the Consolidated Health Economic Evaluation Reporting Standards checklist. RESULTS: Altogether, 25 studies were included in the review. Among the patients refractory to conventional medical treatment, the incremental cost-effectiveness ratio ranged from dominance to 549,335 ?/Quality-Adjusted Life Year compared to the incremental cost-effectiveness ratio associated with conventional medical treatment. When comparing biologics with another biologic treatment, the incremental cost-effectiveness ratio ranged from dominance to 24,012,483 ?/Quality-Adjusted Life Year. A study including both direct and indirect costs produced more favorable incremental cost-effectiveness ratios than those produced by studies including only direct costs. CONCLUSIONS: With a threshold of 35,000 ?/Quality-Adjusted Life Year, biologics seem to be cost-effective for the induction treatment of active and severe inflammatory bowel disease. Between biologics, the cost-effectiveness remains unclear. PMID- 26675295 TI - Initial and Progressive Gray Matter Abnormalities in Insular Gyrus and Temporal Pole in First-Episode Schizophrenia Contrasted With First-Episode Affective Psychosis. AB - Although the insula and temporal pole (TP) of paralimbic regions are important in both affective and cognitive processing, it is not well known whether gray matter volume (GMV) abnormalities in these regions show post-onset progression and differentially affect first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients. To determine whether there are initial and progressive GMV deficits in insula and TP in FESZ and FEAFF (mainly manic) patients, their relative specificity to FESZ or FEAFF, and relationship to symptoms, we conducted a naturalistic study at first hospitalization for psychosis and follow-up ~1.5 years later. Initial 1.5T magnetic resonance imaging (MRI) scans and follow-up scans were on the same scanner. Twenty-two FESZ, 23 FEAFF, and 23 healthy control (HC) subjects were group matched for age, gender, parental socioeconomic status, and handedness. At first hospitalization, FESZ showed significantly smaller bilateral insular GMV compared with FEAFF, and smaller left TP GMV compared with FEAFF and HC. Moreover, on 1.5 years follow-up, FESZ showed progressive GMV decreases in bilateral insula compared with FEAFF and HC, and in TP GMV compared with HC. In contrast, FEAFF showed no progression. Progression of FESZ GMV in both insula and TP was inversely associated with changes in the overall Brief Psychiatric Rating Scale symptom score, indicating less improvement or worsening of symptoms. PMID- 26675297 TI - Correction: MoSET1 (Histone H3K4 Methyltransferase in Magnaporthe oryzae) Regulates Global Gene Expression during Infection-Related Morphogenesis. PMID- 26675296 TI - TGF-betaI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis. AB - Transforming growth factor (TGF-beta)/TGF-beta receptor signal is known to promote cell migration. Up-regulation of TGF-beta in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-beta/TGF-beta receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-beta receptor I (TGF-beta RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low migratory normal or hyperplastic endometrium. Positive correlations between TGF beta RI and OCT4, and either TGF-beta RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-betaI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-betaI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-betaI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-betaI-induced cell migration activity evidenced by wound closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF beta plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-beta-OCT4 signaling to prevent endometriosis in the future. PMID- 26675299 TI - Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss. AB - BACKGROUND AND OBJECTIVES: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses. The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. METHODOLOGY: We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test. RESULTS: We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non-significant trend toward a higher inheritance of the 8.1AH in girls, 63%, P = 0.11 as opposed to boys, 50%, P = 1.00. CONCLUSIONS AND IMPLICATIONS: We did not find that the 8.1AH was significantly more often inherited by live born children of 8.1AH heterozygous RPL women. However our data suggest that there may be a sex-specific effect which would be interesting to explore further, both in RPL and in a background population. PMID- 26675298 TI - Links among inflammation, sexual activity and ovulation: Evolutionary trade-offs and clinical implications. AB - BACKGROUND AND OBJECTIVES: We examined a mechanism that may coordinate trade-offs between reproduction and immune response in healthy women, namely, changes in inflammation across the ovarian cycle. METHODOLOGY: We investigated C-reactive protein (CRP), an inflammation marker, across two consecutive ovarian cycles in 61 Bolivian women. Participants provided saliva samples every other day, and dried blood spots on 5-6 days spread across weeks 2-3 of each cycle. Cycles were characterized as ovulatory/anovulatory based on profiles of reproductive hormones. Participants also reported whether they were sexually partnered with a male or sexually abstinent during the study. RESULTS: High early-cycle, but not late-cycle, CRP was associated with anovulation. High inflammation at the end of one cycle was not associated with anovulation in the subsequent cycle. Among ovulatory cycles, women with sexual partners had significantly lower CRP at midcycle, and higher CRP at follicular and luteal phases; in contrast, sexually abstinent women had little cycle-related change in CRP. In anovulatory cycles, partnership had no effect on CRP. CRP varied significantly with socioeconomic status (higher in better-off than in poorer women). CONCLUSIONS AND IMPLICATIONS: These findings suggest that the cycle-specific effect of inflammation on ovarian function may be a flexible, adaptive mechanism for managing trade-offs between reproduction and immunity. Sociosexual behavior may moderate changes in inflammation across the ovarian cycle, suggesting that these shifts represent evolved mechanisms to manage the trade-offs between reproduction and immunity. Clinically, these findings support considering both menstrual cycle phase and sexual activity in evaluations of pre-menopausal women's CRP concentrations. PMID- 26675300 TI - Association of Obesity and Pediatric Venous Thromboembolism. AB - BACKGROUND: The incidence of venous thromboembolism (VTE) is increasing among pediatric patients in the United States. Previous studies on obesity as a risk factor have produced mixed results. METHODS: We completed a retrospective chart review of patients aged 2 to 18 years with VTE identified by using International Classification of Diseases, Ninth Revision, codes and confirmed by imaging. Patients were admitted between January 2000 and September 2012. Control subjects were matched on age, gender, and the presence of a central venous catheter. Data were collected on weight, height, and risk factors, including bacteremia, ICU admission, immobilization, use of oral contraceptives, and malignancy. Underweight patients and those without documented height and weight data were excluded. Independent predictors of VTE risk were identified by using univariate and multivariate analyses. RESULTS: We identified 88 patients plus 2 matched control subjects per case. The majority of cases were nonembolic events (77%) of the lower extremity (25%) or head and neck (22%) confirmed by ultrasound (43%) or computed tomography scan (41%). A statistically significant association was found between VTE and increased BMI z score (P = .002). In multivariate analysis, BMI z score (odds ratio [OR]: 3.1; P = .007), bacteremia (OR: 4.9; P = .02), ICU stay (OR: 2.5; P = .02), and use of oral contraceptives (OR: 17.4; P < .001) were significant predictors. CONCLUSIONS: In this single-institution study, the diagnosis of VTE was significantly associated with overweight and obesity. Further study is needed to fully define this association. PMID- 26675301 TI - Diversity, Antimicrobial Action and Structure-Activity Relationship of Buffalo Cathelicidins. AB - Cathelicidins are an ancient class of antimicrobial peptides (AMPs) with broad spectrum bactericidal activities. In this study, we investigated the diversity and biological activity of cathelicidins of buffalo, a species known for its disease resistance. A series of new homologs of cathelicidin4 (CATHL4), which were structurally diverse in their antimicrobial domain, was identified in buffalo. AMPs of newly identified buffalo CATHL4s (buCATHL4s) displayed potent antimicrobial activity against selected Gram positive (G+) and Gram negative (G-) bacteria. These peptides were prompt to disrupt the membrane integrity of bacteria and induced specific changes such as blebing, budding, and pore like structure formation on bacterial membrane. The peptides assumed different secondary structure conformations in aqueous and membrane-mimicking environments. Simulation studies suggested that the amphipathic design of buCATHL4 was crucial for water permeation following membrane disruption. A great diversity, broad spectrum antimicrobial action, and ability to induce an inflammatory response indicated the pleiotropic role of cathelicidins in innate immunity of buffalo. This study suggests short buffalo cathelicidin peptides with potent bactericidal properties and low cytotoxicity have potential translational applications for the development of novel antibiotics and antimicrobial peptidomimetics. PMID- 26675302 TI - Onco-proteogenomics identifies urinary S100A9 and GRN as potential combinatorial biomarkers for early diagnosis of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC), the major type of liver cancer, is among the most lethal cancers owing to its aggressive nature and frequently late detection. Therefore, the possibility to identify early diagnostic markers could be of significant benefit. Urine has especially become one of the most attractive body fluids in biomarker discovery as it can be obtained non-invasively in large quantities and is stable as compared with other body fluids. To identify potential protein biomarker for early diagnosis of HCC, we explored protein expression profiles in urine from HCC patients and normal controls (n = 44) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry (nanoLC-MS/MS) and stable isotope dimethyl labeling. We have systematically mapped 91 proteins with differential expressions (p < 0.05), which included 8 down-regulated microtubule proteins and 83 up-regulated proteins involved in signal and inflammation response. Further integrated proteogenomic approach composed of proteomic, genomic and transcriptomic analysis identified that S100A9 and GRN were co-amplified (p < 0.001) and co-expressed (p < 0.01) in HCC tumors and urine samples. In addition, the amplifications of S100A9 or GRN were found to be associated with poor survival in HCC patients, and their co amplification was also prognosed worse overall survival than individual ones. Our results suggest that urinary S100A9 and GRN as potential combinatorial biomarkers can be applied to early diagnosis of hepatocellular carcinoma and highlight the utility of onco-proteogenomics for identifying protein markers that can be applied to disease-oriented translational medicine. PMID- 26675304 TI - Design of a beneficial product for newborn calves by combining Lactobacilli, minerals, and vitamins. AB - Diarrhea is one of the most frequent diseases affecting newborn calves in intensive systems. Several strategies were proposed to protect and improve health, such as probiotics. This work was directed to design a product containing freeze-dried bacteria, vitamins, and minerals, as well as to optimize conditions with lyoprotectors, combine strains and add vitamins, minerals, and inulin to the product. The lyoprotectors were milk, milk-whey, and actose, and products were stored for 6 months at 4 degrees C. Combined bacteria were freeze-dried in milk and the final products were added with minerals, vitamins, and insulin. The viable cells were determined by the plate count assay and antibiotic profiles to differentiate strains. Lactobacillus johnsonii CRL1693, L. murinus CRL1695, L. mucosae CRL1696, L. salivarius CRL1702, L. amylovorus CRL1697, and Enterococcus faecium CRL1703 were evaluated. The optimal conditions were different for each strain. Milk and milk whey maintained the viability during the process and storage after 6 months for most of the strains, except for L. johnsonii. Lactose did not improve cell's recovery. L. murinus was viable for 6 months in all the conditions, with similar results in enterococci. In strains combined before freeze-dried, the viability decreased deeply, showing that one-step process with bacteria mixtures, vitamins, and minerals were not adequate. Freeze-dried resistance depends on each strain and must be lyophilized individually. PMID- 26675303 TI - Dental opioid prescribing practices and risk mitigation strategy implementation: Identification of potential targets for provider-level intervention. AB - BACKGROUND: Given the regular use of immediate-release opioids for dental pain management, as well as documented opioid misuse among dental patients, the dental visit may provide a viable point of intervention to screen, identify, and educate patients regarding the risks associated with prescription opioid misuse and diversion. The aims of this statewide survey of dental practitioners were to assess (a) awareness of the scope of prescription opioid misuse and diversion; (b) current opioid prescribing practices; (c) use of and opinions regarding risk mitigation strategies; and (d) use and perceived utility of drug monitoring programs. METHODS: This cross-sectional study surveyed dentists (N = 87) participating in statewide professional and alumni organizations. Dentists were invited via e-mail and listserv announcement to participate in a one-time, online, 59-item, self-administered survey. RESULTS: A majority of respondents reported prescribing opioids (n = 66; 75.8%). A minority of respondents (n = 38; 44%) reported regularly screening for current prescription drug abuse. Dentists reported low rates of requesting prior medical records (n = 5; 5.8%). Only 38% (n = 33) of respondents had ever accessed a prescription drug monitoring program (PDMP), and only 4 (4.7%) consistently used a PDMP. Dentists reporting prior training in drug diversion were significantly more likely to have accessed their PDMP, P < .01. Interest in continuing education regarding assessment of prescription drug abuse/diversion and use of drug monitoring programs was high. CONCLUSIONS: Although most dentists received training related to prescribing opioids, findings identified a gap in existing dental training in the assessment/identification of prescription opioid misuse and diversion. Findings also identified gaps in the implementation of recommended risk mitigation strategies, including screening for prescription drug abuse, consistent provision of patient education, and use of a PDMP prior to prescribing opioids. PMID- 26675305 TI - Growth of sub-nanometric palladium clusters on boron nitride nanotubes: a DFT study. AB - A QM/MM investigation is reported dealing with the nucleation and growth of small palladium clusters, up to Pd8, on the outer surface of a suitable model of boron nitride nanotubes (BNNTs). It is shown that BNNTs could have a template effect on the cluster growth, which is due to the interplay between Pd-N and Pd-Pd interactions as well as due to the matching of the B3N3 ring and the Pd(111) face arrangement. The values for the cluster adsorption energies reveal a relatively strong physisorption, which suggests that under particular conditions the BNNTs could be used as supports for the preparation of shape-controlled metal clusters. PMID- 26675307 TI - Sesquiterpenoids from the roots of Vladimiria muliensis. AB - An unusual aromadendrane-type sesquiterpenoid with a rare hemiketal-containing 10/3 ring system, named vladimuliecin C (1), and one new eudesmane-type sesquiterpenoid, named vladimuliecin D (4), together with four known sesquiterpenoids, were isolated from the roots of Vladimiria muliensis. The structures of these compounds were elucidated by analysis of spectroscopic data. The absolute configuration of 1 was assigned by X-ray diffraction analysis. A possible biosynthetic process for the formation of 1 is proposed. Compound 1 showed moderate cytotoxicity against three human tumor cell lines. PMID- 26675308 TI - Paenibacillus cathormii sp. nov., isolated from tree bark. AB - A Gram-stain-positive, facultatively anaerobic, rod-shaped and endospore-forming bacterium, strain BK114-2T isolated from tree bark in Thailand was characterized taxonomically using a polyphasic approach. Analysis based on comparison of 16S rRNA gene sequences indicated that strain BK114-2T was affiliated to the genus Paenibacillus, and was closely related to Paenibacillus timonensis 2301032T (96.7 % 16S rRNA gene sequence similarity), Paenibacillus phoenicis 3PO2SAT (96.6 %) and Paenibacillus barengoltzii SAFN-016T (96.4 %). Strain BK114-2T contained meso diaminopimelic acid in its cell-wall peptidoglycan. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unknown phospholipids, five unknown aminophospholipids and six unknown lipids. The only menaquinone detected was MK-7 and the dominant cellular fatty acids were C16 : 0 (22.9 %), anteiso-C15 : 0 (22.6 %), iso-C16 : 0 (19.4 %) and anteiso-C17 : 0 (14.7 %). The DNA G+C content was 52.0 mol%. Based on these results, strain BK114-2T repreesents a novel species of the genus Paenibacillus, for which the name Paenibacillus cathormii sp. nov. is proposed. The type strain is BK114-2T ( = KCTC 33251T = TISTR 2282T). PMID- 26675309 TI - Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway. AB - BACKGROUND: Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti tumor effects. In this study, we investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells. METHODS: The anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin. RESULTS: Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB 231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3 kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21Cip1 (p21) and p27kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c. CONCLUSION: Taken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer. PMID- 26675311 TI - Protein species-specific characterization of conformational change induced by multisite phosphorylation. AB - Phosphorylation is a central mechanism for regulating the structure and function of proteins in the cell, but accurate characterization of a specific protein phospho-species is challenging due to the difficulty of separating it from other species, as well as the limitations of the traditional structural methods. By using selective top-down ETD, we were able to identify six specific phospho species of calmodulin (CaM). Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third. By combining top-down ETD with hydrogen/deuterium exchange, the impact of phosphorylation on CaM's structure was elucidated in a species-specific manner. A negligible structural effect was observed for mono-phosphorylation at Ser81, or di-phosphorylation at Ser81-Thr79, or tri-phosphorylation at Ser81-Thr79-Ser101 or Ser81-Thr79-Thr117. However, it was found that a significant phosphorylation-induced conformational change in CaM was caused by simultaneous phosphorylation at Ser101 and Thr117. The dramatically increased deuterium incorporation for residues between 102 and 119 strongly suggests that the structure of this region has been greatly changed. PMID- 26675306 TI - Molecular profiling of childhood cancer: Biomarkers and novel therapies. AB - BACKGROUND: Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. SCOPE OF REVIEW: This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. MAJOR CONCLUSIONS: There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. GENERAL SIGNIFICANCE: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations. PMID- 26675313 TI - A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy. AB - Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The 'biological optimisation' considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach. PMID- 26675312 TI - Vesicle Motion during Sustained Exocytosis in Chromaffin Cells: Numerical Model Based on Amperometric Measurements. AB - Chromaffin cells release catecholamines by exocytosis, a process that includes vesicle docking, priming and fusion. Although all these steps have been intensively studied, some aspects of their mechanisms, particularly those regarding vesicle transport to the active sites situated at the membrane, are still unclear. In this work, we show that it is possible to extract information on vesicle motion in Chromaffin cells from the combination of Langevin simulations and amperometric measurements. We developed a numerical model based on Langevin simulations of vesicle motion towards the cell membrane and on the statistical analysis of vesicle arrival times. We also performed amperometric experiments in bovine-adrenal Chromaffin cells under Ba2+ stimulation to capture neurotransmitter releases during sustained exocytosis. In the sustained phase, each amperometric peak can be related to a single release from a new vesicle arriving at the active site. The amperometric signal can then be mapped into a spike-series of release events. We normalized the spike-series resulting from the current peaks using a time-rescaling transformation, thus making signals coming from different cells comparable. We discuss why the obtained spike-series may contain information about the motion of all vesicles leading to release of catecholamines. We show that the release statistics in our experiments considerably deviate from Poisson processes. Moreover, the interspike-time probability is reasonably well described by two-parameter gamma distributions. In order to interpret this result we computed the vesicles' arrival statistics from our Langevin simulations. As expected, assuming purely diffusive vesicle motion we obtain Poisson statistics. However, if we assume that all vesicles are guided toward the membrane by an attractive harmonic potential, simulations also lead to gamma distributions of the interspike-time probability, in remarkably good agreement with experiment. We also show that including the fusion-time statistics in our model does not produce any significant changes on the results. These findings indicate that the motion of the whole ensemble of vesicles towards the membrane is directed and reflected in the amperometric signals. Our results confirm the conclusions of previous imaging studies performed on single vesicles that vesicles' motion underneath plasma membranes is not purely random, but biased towards the membrane. PMID- 26675314 TI - Mechanisms And Prevention Of TAVI-Related Cerebrovascular Events. AB - Introduction of transcatheter aortic valve implantation (TAVI) has resulted in a paradigm shift in the treatment of patients with high risk or inoperable severe aortic stenosis. This article aims to comprehensively review the mechanisms of neurological injury per se, the read-outs of cerebrovascular events, and strategies currently used to predict and prevent stroke in transcatheter aortic valve implantation. PMID- 26675310 TI - Coalescent Modelling Suggests Recent Secondary-Contact of Cryptic Penguin Species. AB - Molecular genetic analyses present powerful tools for elucidating demographic and biogeographic histories of taxa. Here we present genetic evidence showing a dynamic history for two cryptic lineages within Eudyptula, the world's smallest penguin. Specifically, we use a suite of genetic markers to reveal that two congeneric taxa ('Australia' and 'New Zealand') co-occur in southern New Zealand, with only low levels of hybridization. Coalescent modelling suggests that the Australian little penguin only recently expanded into southern New Zealand. Analyses conducted under time-dependent molecular evolutionary rates lend support to the hypothesis of recent anthropogenic turnover, consistent with shifts detected in several other New Zealand coastal vertebrate taxa. This apparent turnover event highlights the dynamic nature of the region's coastal ecosystem. PMID- 26675315 TI - Pregnancy Associated Breast Cancer: Awareness is the Key to Diagnosis -A Case Report. AB - Pregnancy-associated breast cancer (PABC) is defined as breast cancer that occurs during pregnancy or within one year of delivery. PABCs are typically found at advanced stage and are reported to have higher recurrence and mortality rates as compared to non PABC. Although it is said to be rare its incidence is increasing. Very little data is available on PABC among Indian women. Delay in diagnosis is one of the major causes of aggressive presentation of PABC. This is due to the fact that most of the lesions presenting during this period are benign and lactational changes hamper the detection of mass clinically as well as by various investigative methods. Paget's disease of breast, usually reported in elderly woman, when occurs in lactating breast may mimic benign eczematous lesion. Increased awareness among patients as well as clinicians is required to detect this highly aggressive form of breast cancer at an early and treatable stage. Treatment is by multidisciplinary approach and depends upon the gestational stage. Here we report a case of PABC in a lactating woman presenting with Paget's disease because such case may be under diagnosed as breast feeding related lesion leading to delayed diagnosis. PMID- 26675316 TI - Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones. AB - Background Determination of the role of steroid hormones in expression and regulation of endometrial glucose transport 4 (GLUT4) in humans is important for understanding endometrial disorders such as polycystic ovary syndrome (PCOS), a common hormone-imbalance disease. Methods Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia and from PCOS patients with or without hyperplasia. In addition, endometrial tissues from postmenopausal women were incubated with human chorionic gonadotropin (hCG, 10 IU/ml), 17beta-estradiol (E2, 10 nM), progesterone (P4, 100 nM), or a combination of E2 and P4 for 24 h. The expression of GLUT4 was measured at the mRNA level using quantitative real-time polymerase chain reaction (qRT PCR) and at the protein level using Western blot analysis and immunohistochemistry. Results A cyclical change in GLUT4 expression pattern was observed in non-PCOS patients, and a high level of GLUT4 expression was seen in the proliferative phase compared to the secretory phase. Low levels of GLUT4 expression were found in PCOS patients compared to menstrual cycle phase-matched non-PCOS patients, and there was no significant change in GLUT4 expression in PCOS patients during the menstrual cycle. GLUT4 was localized in both epithelial and stromal cells, with notable changes in epithelial cells. We postulate that decreased GLUT4 expression might be regulated by steroid hormones. In support of this, we showed that in cultured endometrial tissues hCG and E2 alone had no effect on GLUT4 expression. However, P4 alone and P4 in combination with E2 decreased GLUT4 expression. Compared with non-PCOS controls, PCOS patients with endometrial hyperplasia exhibited decreased GLUT4 expression in particular in the epithelial cells. Conclusion We conclude that P4 can induce changes in endometrial GLUT4 expression during the menstrual cycle and that abnormal hormonal conditions such as PCOS disrupt normal patterns of GLUT4 expression in endometrial cells. PMID- 26675317 TI - Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty. AB - BACKGROUND: Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. AIMS: To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. METHODS: A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. RESULTS: E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. CONCLUSION: Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment. PMID- 26675318 TI - The relationship between Bordetella pertussis genotype and clinical severity in Australian children with pertussis. AB - OBJECTIVES: Changes in circulating Bordetella pertussis genotypes, including a novel pertussis toxin promoter ptxP3 allele and absence of pertactin (Prn) antigen, have been reported from several countries but limited data on relative severity are available. We compared markers of disease severity in children with B. pertussis infection due to strains of differing genotype. METHODS: Culture confirmed cases presenting to tertiary paediatric hospitals in three Australian states between 2008 and 2012 were classified as severe if they required a hospital stay greater than seven days, were admitted to intensive care, or if death occurred. Associations between age, vaccination, genotype and severity were assessed. RESULTS: Of 199 pertussis cases, 81 (41%) were <3 months, including 32/39 (82%) of severe cases. The proportion of isolates from these cases that were Prn deficient increased markedly between 2008 and 2012. Of B. pertussis isolates, the proportion considered severe was similar for Prn positive (27/128, 21%) and Prn deficient (12/71, 17%) cases but only 1/22 (4.5%) of non ptxP3 cases were severe versus 38/177 (21.4%) ptxP3 positive. Adjusting for ptxP type, vaccination status and age, disease severity was not significantly associated with Prn status (RRA: 0.95, [0.57-1.56]; p = 0.83). CONCLUSIONS: In children, we found no relationship between Prn status and markers of severe pertussis. An increased proportion of severe disease in isolates with the ptxP3 allele was observed. PMID- 26675319 TI - Estimation of sigma-Donation and pi-Backdonation of Cyclic Alkyl(amino) Carbene Containing Compounds. AB - Herein, we present a general method for a reliable estimation of the extent of pi backdonation (CcAAC<-E) of the bonded element (E) to the carbene carbon atom and CcAAC->E sigma-donation. The CcAAC<-E pi-backdonation has a significant effect on the electronic environments of the (15)N nucleus. The estimation of the pi backdonation has been achieved by recording the chemical shift values of the (15)N nuclei via two-dimensional heteronuclear multiple-bond correlation spectroscopy. The chemical shift values of the (15)N nuclei of several cAAC containing compounds and/or complexes were recorded. The (15)N nuclear magnetic resonance chemical shift values are in the range from -130 to -315 ppm. When the cAAC forms a coordinate sigma-bond (CcAAC->E), the chemical shift values of the (15)N nuclei are around -160 ppm. In case the cAAC is bound to a cationic species, the numerical chemical shift value of the (15)N nucleus is downfield shifted (-130 to -148 ppm). The numerical values of the (15)N nuclei fall in the range from -170 to -200 ppm when sigma-donation (CcAAC->E) of cAAC is stronger than CcAAC<-E pi-backacceptance. The pi-backacceptance of cAAC is stronger than sigma-donation, when the chemical shift values of the (15)N nuclei are observed below -220 ppm. Electron density and charge transfer between CcAAC and E are quantified using natural bonding orbital analysis and charge decomposition analysis techniques. The experimental results have been correlated with the theoretical calculations. They are in good agreement. PMID- 26675320 TI - Clinical features of infectious keratitis at a tertiary referral center in a rural area of Korea. AB - PURPOSE: To evaluate clinical features of infectious keratitis at a tertiary referral center in a rural area of Korea. RESULTS: This was a retrospective study. Medical records of 70 patients who were diagnosed with infectious keratitis and underwent corneal culture were reviewed. Data including demographics, predisposing factors, and microbiological profiles were collected and analyzed. RESULTS: Age distribution showed one peak at sixth and seventh decade, and 48 patients (68.6%) were >=50 years old. The male to female ratio was 43 (61.4%):27 (38.6%). Ocular surface disease was the most frequently found (48 cases, 68.6%). Gram-positive bacteria were most common (ten patients, 66.7%), followed by Gram-negative bacteria (three patients, 20%) and fungi (two patients, 13.3%). In this study, 34.3% of patients were treated by at least one topical antimicrobial before culture. Patients who received topical therapy before culture showed positive culture rate of 16.7%, and patients who underwent corneal culture without topical antibiotics showed positive culture rate of 23.9%. However, there was no statistically significant difference between the two groups in positive culture rate (P=0.554). CONCLUSION: The proportions of the elderly and male patients were higher than the young and female patients, respectively. Gram-positive bacteria were the most common pathogens, and ocular surface disease was the most common predisposing factor. PMID- 26675321 TI - Descriptive Epidemiology of Musculoskeletal Injuries and Concussions in the National Football League, 2012-2014. AB - BACKGROUND: The risk of all-cause injury and concussion associated with football is significant. The National Football League (NFL) has implemented changes to increase player safety warranting investigation into the incidence and patterns of injury. PURPOSE: To document the incidence and patterns of all-cause injury and concussions in the NFL. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury data were collected prospectively from official NFL injury reports over 2 regular seasons from 2012 to 2014, with identification of injury incidence rates and patterns. Concussion rate ratios were calculated using previously reported NFL rates. RESULTS: A total of 4284 injuries were identified, including 301 concussions. The all-cause injury rate was 395.8 per 1000 athletes at risk (AAR) and concussion incidence was 27.8 per 1000 AAR. Only 2.3% of team games were injury free. Wide receivers, tight ends, and defensive backs had the highest incidence of injury and concussion. Concussion incidence was 1.61-fold higher in 2012 to 2014 compared with 2002 to 2007. The knee was injured most frequently, followed by the ankle, hamstring, shoulder, and head. CONCLUSION: The incidence of all-cause injury and concussion in the NFL is significant. Concussion injury rates are higher than previous reports, potentially reflecting an improvement in recognition and awareness. Injury prevention efforts should continue to reduce the prevalence of injury associated with football. PMID- 26675322 TI - Inferior vena cava/aorta diameter index in the assessment of the body fluid status - a comparative study of measurements performed by experienced and inexperienced examiners in a group of young adults. AB - The assessment of the body fluid status is one the most challenging tasks in clinical practice. Although there are many methods to assess the body fluid status of patients, none of them is fully satisfactory in contemporary medical sciences. In the article below, we compare the results of measurements performed by experienced and inexperienced examiners based on the inferior vena cava/aorta diameter index in a sonographic hydration assessment. The study enrolled 50 young students at the age of 19-26 (the median age was 22.95) including 27 women and 23 men. The volunteers were examined in the supine position with GE Logiq 7 system and a convex transducer with the frequency of 2-5 MHz. The measurements were performed in the longitudinal and transverse planes by two inexperienced examiners - the authors of this paper, following a four-hour training conducted by an experienced sonographer. The longitudinal values of the inferior vena cava/aorta diameter index obtained in this study were similar to those found in the literature. The reference value for the inferior vena cava/aorta index determined by Kosiak et al., which constituted 1.2 +/- 2 SD, for SD = 0.17, was similar to the values obtained by the authors of this paper which equaled 1.2286 +/- 2 SD, for SD = 0.2. The article presented below proves that measuring the inferior vena cava/aorta diameter index is not a complex examination and it may be performed by physicians with no sonographic experience. Furthermore, the paper demonstrates that the inferior vena cava/aorta diameter index measured in the transverse plane is similar to the inferior vena cava/aorta diameter index determined in the longitudinal plane. Thus, both measurements may be used interchangeably to assess the hydration status of patients. PMID- 26675323 TI - Preparation and antibacterial properties of O-carboxymethyl chitosan/lincomycin hydrogels. AB - In this study, O-carboxymethyl chitosan (O-CMCS) was synthesized from chitosan and monochloroacetic acid. Then O-CMCS hydrogel was prepared by 1-(3 dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N hydroxysuccinimide (NHS) in which the lincomycin was packaged. The Fourier transform infrared spectrum and scanning electron microscopy were adopted to characterize the structure and morphology of the product. The influences of dosage of EDC/NHS and concentration of O-CMCS on the swelling properties of the hydrogels were investigated. The hydrogels performed good swelling capacities and obvious pH-sensitive properties. The antibacterial activities of the hydrogels were tested against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Compared with pure O-CMCS hydrogels, the antibacterial activities of O-CMCS/lincomycin hydrogels were significantly improved with the increase in the concentration of lincomycin against E. coli and S. aureus. With the increase in dosage of crosslinking agent or concentration of O-CMCS, the antibacterial activities both decreased gradually against the two bacteria. O-CMCS/lincomycin hydrogel was expected to be used for antibacterial material in view of its significant antibacterial activities. PMID- 26675324 TI - Harlequin Ichthyosis: Prenatal Diagnosis of a Rare Yet Severe Genetic Dermatosis. AB - Harlequin Ichthyosis (HI) is an extremely rare genetic skin disorder. It is the most severe type of ichthyosis. It is characterized by thickened, dry, rough and armor like plates of skin with deep cracks in between. Alternative names for HI include- keratosis diffusafetalis, ichthyosis congenital, icthyosis fetalis, harlequin fetus and icthyosis congenital gravior. It is an autosomal recessive disorder with the majority of affected individuals being homozygous for mutation in the ABCA 12 gene. This condition presents with a wide range of severity and symptoms. Affected neonates usually do not survive beyond first few days of life. We are presenting prenatal diagnosis of a case of this rare condition. PMID- 26675325 TI - Unique Clinicopathology of Proximal Gastric Carcinoma: A Critical Review. AB - BACKGROUND: Gastric cancer is a heterogeneous disease with respect to its molecular and histopathological features. Proximal gastric carcinoma (PGC) and distal gastric carcinoma (DGC) are two distinct clinical entities, suggesting the existence of different pathogenic mechanisms. PGC arises in a narrow region of the proximal stomach below the gastroesophageal junction. It accounts for around half of gastric cancers in men, with an increasing incidence worldwide and a predominance in elderly males. SUMMARY: At present, the pathogenic mechanisms involved in the onset of PGC remain unknown. This mini-review presents the most recent findings on the pathology and natural history of this widespread and frequently fatal cancer. KEY MESSAGE: PGC has unique clinicopathological characteristics distinct from esophageal adenocarcinoma and DGC. PRACTICAL IMPLICATIONS: Patients with a high risk for PGC, such as elderly obese men, should undergo upper endoscopy for early detection and appropriate endoscopic therapy in the early stages of disease. Once it has progressed, the cancer is more easily spread, although the current staging systems are not perfectly adapted to the disease. PGC should be staged and treated as a gastric cancer. A separate staging system and genomic studies on this cancer are urgently needed for optimal patient management and appropriate disease prevention. PMID- 26675326 TI - Validity of Cancer Antigen-125 (CA-125) and Risk of Malignancy Index (RMI) in the Diagnosis of Ovarian Cancer. AB - OBJECTIVE: We sought to determine the validity of cancer antigen 125 (CA-125) and the risk of malignancy index (RMI) in the diagnosis of ovarian cancer in women presenting with adnexal lesions of various histopathology types. METHODS: This retrospective cross- sectional study included all women with adnexal lesions who were evaluated at the Royal Hospital, Oman, between January 2012 and December 2014. The inclusion criteria included women who underwent surgical intervention and who had preoperative CA-125 testing and pelvic ultrasound in the work-up plan of their management. The surgical intervention was usually followed by a histopathological diagnosis of the nature of the lesion, which was used as the gold standard for the evaluation of both CA-125 and RMI. RESULTS: The cohort included 361 women who had serum CA-125 and pelvic ultrasound prior to the surgical intervention of the adnexal lesion. Of these women, 61 (17%) had malignant ovarian lesions. Using the proposed cut-off 35 U/ml for CA-125 and 200 for RMI, the CA-125 test was more sensitive for detecting the majority of malignant ovarian tumors compared to the RMI (69% vs. 57%). Both tests were more sensitive in detecting epithelial ovarian cancer compared to other ovarian cancers. However, RMI was more specific in excluding benign ovarian lesions compared to CA-125 (81% vs. 68%). Additionally, RMI had a better area under the curve compared to CA-125 (0.771 vs. 0.745; p<0.005). Lowering the RMI cut-off to 150 resulted in a better sensitivity (62% vs. 57%) and had an acceptable specificity (78% vs. 81%) compared to a cut-off of 200. CONCLUSION: Both CA-125 and RMI have good validity in the diagnosis of ovarian tumors. CA-125 has higher sensitivity; however, RMI has higher specificity. In combination, CA-125 might be more valid for the diagnosis of malignant ovarian cancer while RMI is more valid for excluding the diagnosis of these tumors. Differential use of these two tools will improve the triage of women with suspected ovarian tumors since both are measured in their work-up. We recommended the use of both tools in primary care to reduce referral to gynecology or oncology units. PMID- 26675327 TI - Peliosis hepatis: Personal experience and literature review. AB - Peliosis hepatis (PH) is a disease characterized by multiple and small, blood filled cysts within the parenchymatous organs. PH is a very rare disease, more common in adults, and when it affects the liver, it comes to the surgeon's attention only in an extremely urgent situation after the lesion's rupture with the resulting hemoperitoneum. This report describes the case of a 29-year-old woman affected by recurring abdominal pain. Computed tomography scans showed a hepatic lesion formed by multiple hypodense areas, which showed an early acquisition of the contrast during the arterial phase. Furthermore, it remained isodense with the remaining parenchyma during the late venous phase. We decided on performing a liver resection of segment VII while avoiding a biopsy for safety reasons. The histopathologic examination confirmed the diagnosis of focal PH. PH should always be considered in the differential diagnosis of hepatic lesions. Clinicians should discuss the possible causes and issues related to the differential diagnosis in addition to the appropriate therapeutic approach. The fortuitous finding of a lesion, potentially compatible with PH, requires elective surgery with diagnostic and therapeutic intents. The main aim is to prevent the risk of a sudden bleeding that, in absence of properly equipped structures, may have a fatal outcome. PMID- 26675328 TI - Reading the Combinatorial Histone Language. AB - Histones are subject to frequent combinatorial post-translational modifications (PTMs), forming a complex chemical "language" that is interpreted by PTM-specific histone-interacting protein modules (reader domains). These specific interactions are thought to instruct gene expression and downstream biological functions. While the majority of studies have focused on individual modifications, our current understanding of the combinatorial PTM patterns on histones is starting to emerge, benefiting from the convergence of multiple technologies. Here, we review the key technical advances and progress on discovery and characterization of combinatorial histone PTM patterns. We focus on the interactions between reader domains and combinatorial PTMs, which is essential for understanding the mechanism and biological meaning of establishing and interpreting information embedded in histone PTM patterns. PMID- 26675330 TI - Images in Vascular Medicine. Visceral fibromuscular dysplasia in a patient with chronic abdominal pain. PMID- 26675329 TI - A low ratio of n-6/n-3 polyunsaturated fatty acids suppresses matrix metalloproteinase 13 expression and reduces adjuvant-induced arthritis in rats. AB - Increased expression of matrix metalloproteinase 13 (MMP13) in chondrocytes contributes to the development of osteoarthritis. The hypothesis of this study was that diet with a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced MMP13 expression in inflammatory chondrocytes in vitro and in vivo. Human chondrocytes were cultured with different ratios of linoleic acid (LA, n-6 PUFA) to alpha-linolenic acid (n-3 PUFA) from 1:1 to 10:1. Proliferation of chondrocytes, MMP13 protein and mRNA levels were detected, respectively. Sprague-Dawley rats (n=30) were fed diets containing different ratios of n-6/n-3 PUFA. Freund's complete adjuvant was injected to make the model of arthritis. Paw swelling rate was measured and all rats were euthanized after 6 weeks of treatment. Serum MMP13 and IL-1 were measured by enzyme-linked immunosorbent assay. Joint histological sections were stained with safranin-O Fast Green to evaluate cartilage damage. Low ratio of LA/alpha-linolenic acid decreased the mRNA and protein levels of MMP13 but did not affect chondrocytes proliferation. Ratios of PUFA such as 1:1 and 2:1 significantly reduced paw swelling rate, and serum MMP13 and IL-1 levels in a rat model. Histological staining showed that ratios of 1:1 and 2:1 PUFA significantly alleviated cartilage damage in adjuvant-induced arthritis. A ratio of n-6/n-3 PUFA of 1:1 showed the strongest inhibitory effect on MMP13. Our results indicate that a low ratio of n-6/n-3 PUFA at 1:1 significantly suppressed MMP13 expression both in vitro and in vivo and reduced adjuvant-induced arthritis in rats could be a means to control and reduce the symptoms of osteoarthritis. PMID- 26675331 TI - Coronary endothelial dysfunction in non-obstructive coronary artery disease: Risk, pathogenesis, diagnosis and therapy. AB - Up to half of patients with signs and symptoms of stable ischemic heart disease have non-obstructive coronary artery disease (NoCAD). Recent evidence demonstrates that two-thirds of patients with NoCAD have demonstrable coronary endothelial dysfunction represented by microvascular or diffuse epicardial spasm following acetylcholine challenge. Patients with coronary endothelial dysfunction are recognized to have significant health services use and morbidity as well as increased risk of developing flow-limiting coronary artery disease and myocardial events, including death. Currently, there are few centers that test for this etiology owing to lack of knowledge, limited evidence for treatment options and invasive diagnostic strategies. This article reviews the pathophysiology, epidemiology, diagnosis and treatment of coronary endothelial dysfunction as a subgroup of NoCAD. PMID- 26675332 TI - Variations in telomere maintenance and the role of telomerase inhibition in gastrointestinal cancer. AB - Immortalization is an important step toward the malignant transformation of human cells and is critically dependent upon telomere maintenance. There are two known mechanisms to maintain human telomeres. The process of telomere maintenance is either mediated through activation of the enzyme telomerase or through an alternative mechanism of telomere lengthening called ALT. While 85% of all human tumors show reactivation of telomerase, the remaining 15% are able to maintain telomeres via ALT. The therapeutic potential of telomerase inhibitors is currently investigated in a variety of human cancers. Gastrointestinal tumors are highly dependent on telomerase as a mechanism of telomere maintenance, rendering telomeres as well as telomerase potential targets for cancer therapy. This article focuses on the molecular mechanisms of telomere biology and telomerase activation in gastrointestinal cancers and reviews strategies of telomerase inhibition and their potential therapeutic use in these tumor entities. PMID- 26675333 TI - Human NUP98-IQCG fusion protein induces acute myelomonocytic leukemia in mice by dysregulating the Hox/Pbx3 pathway. PMID- 26675334 TI - Shifting the Reactivity of Bis-propargyl Ethers from Garratt-Braverman Cyclization Mode to 1,5-H Shift Pathway To Yield 3,4-Disubstituted Furans: A Combined Experimental and Computational Study. AB - Aryl or vinyl substituted bis-propargyl ethers upon base treatment generally form phthalans via the Garratt-Braverman (GB) cyclization pathway. In a major departure from this usual route, several aryl/vinyl bis-propargyl ethers with one of the acetylenic arms ending up with 2-tetrahydropyranyloxy methyl or ethoxy methyl have been shown to follow the alternative intramolecular 1,5-H shift pathway upon base treatment. The reaction has led to the formation of synthetically as well as biologically important 3,4-disubstituted furan derivatives in good yields. The initially formed E isomer in solution (CDCl3) slowly isomerizes to the Z isomer, indicating greater stability of the latter. The factors affecting the interplay between the 1,5-H shift and GB rearrangement have also been evaluated, and the results are supported by DFT-based computational study. PMID- 26675335 TI - Label-Free Bottom-Up Proteomic Workflow for Simultaneously Assessing the Target Specificity of Covalent Drug Candidates and Their Off-Target Reactivity to Selected Proteins. AB - Although designed covalent inhibitors as drug candidates offer several unique advantages over conventional reversible inhibitors, including high potency and the potential for less frequent dosing, there is a general tendency to avoid the covalent mode of action in drug discovery programs due to concerns regarding immune-mediated toxicity that can arise from indiscriminate reactivity with off target proteins. Therefore, the ability to assess off-target reactivity relative to target specificity is desirable for optimizing covalent drug candidates in the early discovery stage. One concern with current surrogate nucleophile trapping approaches is that they employ a simplistic model nucleophile such as glutathione, which may not reliably reflect the covalent interactions with cellular or extracellular proteins. One way to get a more relevant reactivity assessment is to directly measure the ability of an inhibitor to covalently modify nucelophilic amino acids on biologically relevant proteins, both on- and off-target. In this article, we describe a label-free bottom-up proteomic workflow for simultaneous evaluation of target binding and off-target reactivity of covalent drug candidates to selected proteins at the peptide level. Ibrutinib, a covalent drug targeting the active site of BTK protein, was used as a model compound to demonstrate the feasibility of the workflow. The compound was incubated with a mixture of target protein, Bruton's tyrosine kinase (BTK), and two abundant proteins in blood, hemoglobin (Hb) and human serum albumin (HSA), and then the ibrutinib modification sites were determined utilizing a bottom-up proteomic approach. A non-BTK specific model compound (1) known to modify cysteine residues was also included. By comparing the extent of off-target modifications to the targeted BTK C481 binding in a wide compound concentration range, we were able to determine the concentration where maximum target binding was achieved with minimal off-target reactivity. The generic label-free bottom-up proteomics workflow described in this article should be useful in the rank order assessment of off-target reactivity vs on-target reactivity of covalent drug candidates in the early drug discovery stage. PMID- 26675336 TI - The Effects of Improved Photoelectric Properties of PEDOT:PSS by Two-Step Treatments on the Performance of Polymer Solar Cells Based on PTB7-Th:PC(71)BM. AB - In this paper, we present a smart two-step treated method to simultaneously improve the work function, conductivity, and transmittance of poly(3,4 ethylenedioxythiophene):poly(styrene sulfonate) ( PEDOT: PSS). With the two-step treated PEDOT: PSS, the short-circuit current density of polymer solar cells (PSCs) based on PTB7-Th:PC71BM increases from 13.41 to 22.10 mA/cm(2), and the power conversion efficiency increases from 7.35% to 9.82% with 33% improvement. The underlying mechanisms on performance improvement of PSCs can be summarized as follows: (1) two-step treated PEDOT: PSS with the improved work function and the conductivity, which contributes significantly to the charge collection of PSCs; and (2) two-step treated PEDOT: PSS with higher transmittance, which is of benefit to the light absorption of the active layer in PSCs. PMID- 26675337 TI - Lowering blood glucose during hip surgery does not influence coagulation activation. AB - BACKGROUND: Hyperglycaemia during and after hip surgery is associated with coagulation activation and an increased risk of venous thromboembolism. Whether lowering of glucose levels during hip surgery diminishes coagulation activation is unknown. We investigated the efficacy of the human GLP-1 analogue liraglutide to lower glucose during and after hip surgery and studied its influence on coagulation activation. METHODS: A total of 37 obese subjects who underwent hip surgery were randomized to subcutaneous liraglutide or placebo for 4 consecutive days, starting one day prior to surgery. Glucose levels and coagulation indices at three fixed time-points (pre-operative, 2 h post-operative and 3 days post operative) were measured. RESULTS: Liraglutide reduced glucose at day three post surgery (median glucose (IQR) liraglutide 5.5 (5.2-5.7) vs. placebo 5.8 (5.5 6.2); difference 0.3 mmol/L, P = 0.04). Changes in 6 out of 8 coagulation indices studied did not differ between the two groups. Only D-dimer levels were significantly lower in the liraglutide group at day three post-surgery and FVIII levels were significantly higher in the liraglutide group 2 h post-surgery. CONCLUSION: Although the human GLP-1 analogue liraglutide moderately reduced post operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation. PMID- 26675338 TI - Ultrasound diagnosis of pulmonary sling with proximal stenosis of left pulmonary artery and patent arterial duct. AB - Authors discuss methods of echocardiographic diagnosis of the pulmonary sling with stenosis and hypoplasia of the left pulmonary artery and patent arterial duct with massive left-to-right shunt, based on a case of the newborn with resistant to treatment heart failure, with initial diagnosis of patent ductus arteriosus, referred to surgical treatment. The optimal echocardiographic views permitting establish diagnosis of the pulmonary sling were suggested. The special attention was paid to high parasternal and suprasternal views visualizing vessels of the upper mediastinum as well as characteristic differences between the normal and pathologic picture. The typical features of the echocardiogram suggesting pulmonary sling, like the lack of the left pulmonary artery in its expected position, and the abnormal branching pattern of the right pulmonary artery were indicated. The greatest diagnostic difficulties in visualization of the abnormal route of the left pulmonary artery were related to the presence of air-containing tissues, like lungs and central airways between the ultrasound probe and area of interest. The other was the masking influence of the large patent arterial duct, that may mimic the left pulmonary artery arising from the pulmonary trunk. The other entities requiring differentiation with sling, like aplasia of the left lung, the direct or indirect aortic origin of the left pulmonary artery, were discussed. The role of other visualization technics, like computed 3D tomography, and magnetic nuclear resonance, as well as direct visualization of central airways with bronchoscopy in establishing precise diagnosis were stressed. PMID- 26675339 TI - Utility of a Newly Designed Film Holder for Premolar Bitewing Radiography. AB - INTRODUCTION: Bitewing radiography is a valuable technique for assessment of proximal caries, alveolar crest and periodontal status. Technical errors during radiography result in erroneous radiographic interpretation, misdiagnosis, possible mistreatment or unnecessary exposure of patient for taking a repeat radiograph. AIM: In this study, we aimed to evaluate the efficacy of a film holder modified from the conventional one and compared it with that of conventional film holder. MATERIALS AND METHODS: Our study population comprised of 70 patients who were referred to the Radiology Department for bilateral premolar bitewing radiographs as requested by their attending clinician. Bitewing radiographs in each patient were taken using the newly designed holder in one side and the conventional holder in the other side. The acceptability of the two holders from the perspectives of the technician and patients was determined using a 0-20 point scale. The frequency of overlap and film positioning errors was calculated for each method. RESULTS: The conventional holder had greater acceptability among patients compared to the newly designed holder (mean score of 16.59 versus 13.37). From the technicians' point of view, the newly designed holder was superior to the conventional holder (mean score of 17.33 versus 16.44). The frequency of overlap was lower using the newly designed holder (p<0.001) and it allowed more accurate film positioning (p=0.005). CONCLUSION: The newly designed holder may facilitate the process of radiography for technicians and may be associated with less frequency of radiographic errors compared to the conventional holder. PMID- 26675340 TI - Color Doppler imaging of the retrobulbar vessels in diabetic retinopathy. AB - Diabetes is a metabolic disease characterized by elevated blood glucose level due to impaired insulin secretion and activity. Chronic hyperglycemia leads to functional disorders of numerous organs and to their damage. Vascular lesions belong to the most common late complications of diabetes. Microangiopathic lesions can be found in the eyeball, kidneys and nervous system. Macroangiopathy is associated with coronary and peripheral vessels. Diabetic retinopathy is the most common microangiopathic complication characterized by closure of slight retinal blood vessels and their permeability. Despite intensive research, the pathomechanism that leads to the development and progression of diabetic retinopathy is not fully understood. The examinations used in assessing diabetic retinopathy usually involve imaging of the vessels in the eyeball and the retina. Therefore, the examinations include: fluorescein angiography, optical coherence tomography of the retina, B-mode ultrasound imaging, perimetry and digital retinal photography. There are many papers that discuss the correlations between retrobulbar circulation alterations and progression of diabetic retinopathy based on Doppler sonography. Color Doppler imaging is a non-invasive method enabling measurements of blood flow velocities in small vessels of the eyeball. The most frequently assessed vessels include: the ophthalmic artery, which is the first branch of the internal carotid artery, as well as the central retinal vein and artery, and the posterior ciliary arteries. The analysis of hemodynamic alterations in the retrobulbar vessels may deliver important information concerning circulation in diabetes and help to answer the question whether there is a relation between the progression of diabetic retinopathy and the changes observed in blood flow in the vessels of the eyeball. This paper presents the overview of literature regarding studies on blood flow in the vessels of the eyeball in patients with diabetic retinopathy. PMID- 26675341 TI - MoV2O8 nanostructures: controlled synthesis and lithium storage mechanism. AB - A facile two-step strategy involving a solvothermal method and a subsequent calcining treatment was successfully developed for the preparation of MoV2O8 nanorods in the absence of any surfactants. Acetic acid was chosen as the solvent to provide an acidic environment. The as-synthesized MoV2O8 nanorods were evaluated as an anode material in lithium ion batteries, which showed excellent lithium storage performance in terms of its specific capacity, rate performance, and cycling stability. It could deliver a specific capacity of over 1325 mA h g( 1) after 50 cycles at 0.2 A g(-1), which is much higher than that of bulk MoV2O8 (617 mA h g(-1)). When the cell was cycled at a current density as high as 10.0 A g(-1), it still maintained a high specific capacity of around 570 mA h g(-1). The phase transformation, intercalation-deintercalation and partial redox processes are responsible for the lithium storage mechanism of MoV2O8 based on ex situ X ray diffraction, X-ray photo electron spectroscopy and transmission electron microscopy studies, highlighting a new lithium storage mechanism for ternary metal oxides. PMID- 26675342 TI - High Pressure Vibrational Properties of WS2 Nanotubes. AB - We bring together synchrotron-based infrared and Raman spectroscopies, diamond anvil cell techniques, and an analysis of frequency shifts and lattice dynamics to unveil the vibrational properties of multiwall WS2 nanotubes under compression. While most of the vibrational modes display similar hardening trends, the Raman-active A1g breathing mode is almost twice as responsive, suggesting that the nanotube breakdown pathway under strain proceeds through this displacement. At the same time, the previously unexplored high pressure infrared response provides unexpected insight into the electronic properties of the multiwall WS2 tubes. The development of the localized absorption is fit to a percolation model, indicating that the nanotubes display a modest macroscopic conductivity due to hopping from tube to tube. PMID- 26675343 TI - Ultrasound assessment of the caliber of the arteries in the lower extremities in healthy persons - the dependency on age, sex and morphological parameters of the subjects. AB - AIM: The aim of this paper was to evaluate the caliber of the following arteries in the lower extremities: the common femoral artery, superficial femoral artery, popliteal artery, posterior tibial artery and dorsalis pedis artery and to determine the relation of the calibers to age, sex and morphological parameters of the body such as weight, height and BMI of the subject. MATERIAL: Two hundred and twenty-eight healthy persons aged 18-81 were examined (average +/-SD; 43.1+/ 16.71): 134 women aged 19-74 (43.2+/-15.63) and 94 men aged 18-81 (43+/-18.22). METHODS: The study was conducted with the use of a linear probe of 7.5 MHz frequency. The vascular caliber was assessed after the color map (color Doppler) was placed on a B-mode image. RESULTS: The average and standard deviation values for the calibers of examined vessels were determined. The calibers of all vessels examined in the group of men were statistically significantly larger than those in the group of women. No statistically significant differences between the calibers of the right and left sides were determined. The statistically significant correlations were specified between the age and the caliber of the examined vessels; positive for large femoral arteries and negative for the arteries of the crus and foot. Positive, statistically significant correlations between the caliber and the height, weight and BMI were also reported. CONCLUSIONS: The reported calibers of the arteries in the lower extremities and their relation to age, sex and morphological parameters of the subjects enable the differentiation of the physiological remodeling of the vessels from the pathological processes in e.g. atherosclerosis or hypertension. PMID- 26675344 TI - Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients. AB - BACKGROUND: Several studies suggest that pathological changes in Alzheimer's disease (AD) brain begin around 10-20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Abeta42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. OBJECTIVES: This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from subjects with AD and amnestic mild cognitive impairment (aMCI). METHODS: A targeted proteomics approach has been employed to discover novel CSF biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers. CSF samples from aMCI, AD and control individuals (CTR) were collected and analyzed using a combined redox proteomics approach to identify the specific oxidatively modified proteins in AD and aMCI compared with controls. RESULTS: The majority of carbonylated proteins identified by redox proteomics are found early in the progression of AD, i.e., oxidatively modified CSF proteins were already present in aMCI compared with controls and remain oxidized in AD, thus suggesting that dysfunction of selected proteins initiate many years before severe dementia is diagnosed. CONCLUSIONS: The above findings highlight the presence of early oxidative damage in aMCI before clinical dementia of AD is manifested. The identification of early markers of AD that may be detected peripherally may open new prospective for biomarker studies. PMID- 26675345 TI - A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways. AB - Uncontrolled inflammation is a leading cause of various chronic diseases. Cinnamaldehyde (CA) is a major bioactive compound isolated from the essential oil of the leaves of Cinnamomum osmophloeum kaneh that exhibits anti-inflammatory activity; however, the use of CA is limited by its cytotoxicity. Here, we synthesized three CA derivatives and identified 4-hydroxycinnamaldehyde galactosamine (HCAG) as a low toxicity anti-inflammatory compound in vitro (HCAG IC50 ? 1600 uM; CA IC50=40 uM) and in vivo. HCAG reduced pro-inflammatory mediator expression in LPS-activated macrophages by inhibiting MAPK and PKC alpha/delta phosphorylation, decreasing ROS generation and reducing NF-kappaB activation. HCAG also reduced NLRP3 inflammasome-derived IL-1beta secretion by inhibiting the ATP-mediated phosphorylation of AKT and PKC-alpha/delta. In a mouse model of LPS-induced renal inflammation, we observed reduced albuminuria and a mild degree of glomerular proliferation, glomerular sclerosis and periglomerular inflammation in the HCAG-treated mice compared with the vehicle treated mice. The underlying mechanisms for these renoprotective effects involved: (1) inhibited NLRP3 inflammasome activation; (2) decreased superoxide anion levels and apoptosis; and (3) suppressed activation of NF-kappaB and related downstream inflammatory mediators. PMID- 26675346 TI - Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations. AB - Fludarabine, cyclophosphamide, and rituximab (FCR) is first-line treatment of medically fit chronic lymphocytic leukemia (CLL) patients; however, despite good response rates, many patients eventually relapse. Although recent high-throughput studies have identified novel recurrent genetic lesions in adverse prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, and BIRC3), a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases, selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal before treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid, evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared with wild-type RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology. PMID- 26675347 TI - Pevonedistat, a NEDD8-activating enzyme inhibitor, is active in mantle cell lymphoma and enhances rituximab activity in vivo. AB - Mantle cell lymphoma (MCL) is characterized by an aggressive clinical course and inevitable development of refractory disease, stressing the need to develop alternative therapeutic strategies. To this end, we evaluated pevonedistat (MLN4924), a novel potent and selective NEDD8-activating enzyme inhibitor in a panel of MCL cell lines, primary MCL tumor cells, and 2 distinct murine models of human MCL. Pevonedistat exposure resulted in a dose-, time-, and caspase dependent cell death in the majority of the MCL cell lines and primary tumor cells tested. Of interest, in the MCL cell lines with lower half-maximal inhibitory concentration (0.1-0.5 MUM), pevonedistat induced G1-phase cell cycle arrest, downregulation of Bcl-xL levels, decreased nuclear factor (NF)-kappaB activity, and apoptosis. In addition, pevonedistat exhibited additive/synergistic effects when combined with cytarabine, bendamustine, or rituximab. In vivo, as a single agent, pevonedistat prolonged the survival of 2 MCL-bearing mouse models when compared with controls. Pevonedistat in combination with rituximab led to improved survival compared with rituximab or pevonedistat monotherapy. Our data suggest that pevonedistat has significant activity in MCL preclinical models, possibly related to effects on NF-kappaB activity, Bcl-xL downregulation, and G1 cell cycle arrest. Our findings support further investigation of pevonedistat with or without rituximab in the treatment of MCL. PMID- 26675348 TI - Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. AB - Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/uL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436. PMID- 26675349 TI - Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. AB - Multiple myeloma (MM) is characterized by a highly unstable genome, with aneuploidy observed in nearly all patients. The mechanism causing this karyotypic instability is largely unknown, but recent observations have correlated these abnormalities with dysfunctional DNA damage response. Here, we show that the NAD(+)-dependent deacetylase SIRT6 is highly expressed in MM cells, as an adaptive response to genomic stability, and that high SIRT6 levels are associated with adverse prognosis. Mechanistically, SIRT6 interacts with the transcription factor ELK1 and with the ERK signaling-related gene. By binding to their promoters and deacetylating H3K9 at these sites, SIRT6 downregulates the expression of mitogen-activated protein kinase (MAPK) pathway genes, MAPK signaling, and proliferation. In addition, inactivation of ERK2/p90RSK signaling triggered by high SIRT6 levels increases DNA repair via Chk1 and confers resistance to DNA damage. Using genetic and biochemical studies in vitro and in human MM xenograft models, we show that SIRT6 depletion both enhances proliferation and confers sensitization to DNA-damaging agents. Our findings therefore provide insights into the functional interplay between SIRT6 and DNA repair mechanisms, with implications for both tumorigenesis and the treatment of MM. PMID- 26675350 TI - Human STEAP3 mutations with no phenotypic red cell changes. PMID- 26675352 TI - The Effects of an Online Theory-Based Bone Health Program for Older Adults. AB - An estimated 10 million Americans age 50 and older have osteoporosis, and many experience associated fractures. Although several interventions have been shown to be effective in preventing osteoporosis, their impact on bone health among older adults was limited. The aim of this study was, therefore, to examine the effects of a theory-based online bone health program (Bone Power program) for a large number of older adults. The 8-week program included learning modules, discussion boards, and other resources. Participants ( N = 866; M age = 62.5 years) were recruited online and randomized into a Bone Power or control group. At the end of the intervention, the Bone Power group showed significantly greater improvement over the control group in osteoporosis knowledge, self efficacy/outcome expectations for calcium intake and exercise, and calcium intake and exercise behaviors. This study's findings suggest that online health programs can be effective in improving older adults' knowledge, beliefs, and health behaviors. PMID- 26675351 TI - Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease. AB - Hemolytic diseases, such as sickle cell anemia and thalassemia, are characterized by enhanced release of hemoglobin and heme into the circulation, heme-iron loading of reticulo-endothelial system macrophages, and chronic inflammation. Here we show that in addition to activating the vascular endothelium, hemoglobin and heme excess alters the macrophage phenotype in sickle cell disease. We demonstrate that exposure of cultured macrophages to hemolytic aged red blood cells, heme, or iron causes their functional phenotypic change toward a proinflammatory state. In addition, hemolysis and macrophage heme/iron accumulation in a mouse model of sickle disease trigger similar proinflammatory phenotypic alterations in hepatic macrophages. On the mechanistic level, this critically depends on reactive oxygen species production and activation of the Toll-like receptor 4 signaling pathway. We further demonstrate that the heme scavenger hemopexin protects reticulo-endothelial macrophages from heme overload in heme-loaded Hx-null mice and reduces production of cytokines and reactive oxygen species. Importantly, in sickle mice, the administration of human exogenous hemopexin attenuates the inflammatory phenotype of macrophages. Taken together, our data suggest that therapeutic administration of hemopexin is beneficial to counteract heme-driven macrophage-mediated inflammation and its pathophysiologic consequences in sickle cell disease. PMID- 26675353 TI - Viewing Art on a Tablet Computer: A Well-Being Intervention for People With Dementia and Their Caregivers. AB - BACKGROUND: Art-based interventions have been shown to be beneficial for the well being of people with dementia and their caregivers. This article explored whether such interventions can be delivered via a touchscreen tablet device displaying art images. METHOD: Twelve pairs of volunteers with dementia and informal caregivers were recruited (N = 24). A quasi-experimental mixed-methods within subjects study evaluated the well-being impacts of art viewing using visual analogue scales and explored participant experiences with thematic analysis. FINDINGS: Quantitative results before Bonferroni correction showed a significant effect for change in composite well-being from Session 1 to Session 5 but this became non-significant after the correction was applied. Well-being subdomains generally increased with number of sessions. Qualitative findings included changes in cognition, behavior, mood, and relationships. These changes tended to be viewed positively. CONCLUSION: The results suggest touchscreen-based art interventions could yield well-being benefits for this population. A larger-scale controlled study would help determine whether wider dementia care practice implications can be drawn. PMID- 26675354 TI - Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma. AB - BACKGROUND: Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate. OBJECTIVE: To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. METHODS: The authors retrospectively analyzed 120 PCM samples. We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes. RESULTS: Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone. LIMITATIONS: This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. CONCLUSIONS: Immunolabeling increased detection of LVI in PCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis. PMID- 26675355 TI - Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid: A Report of a Case With Molecular Analysis. PMID- 26675356 TI - Novel Use of Preoperative Epidermal Coloring of Very Small Dermatological Specimens-Protocol for Reduction of Lost Specimens. AB - Small tissue biopsies are often difficult to visualize and can be easily lost or mishandled. The authors hypothesized that full epidermal surface coloration of small skin lesions with a sterile skin marker (gentian violet ink) before performing shave biopsy would make small gross specimens easier to identify without impacting microscopic appearance. Live evaluation of 4 inked and 4 noninked gross (2-3 mm) specimens in covered and uncovered formalin-containing jars by 50 consecutive health care personnel demonstrated that inked specimens were significantly (P < 0.001) easier to visualize than noninked specimens. Additionally, a blinded dermatopathologist evaluated 25 inked and 25 noninked specimens microscopically. Utilization of this inking process did not interfere with histopathologic assessment or impede diagnosis. This pilot study describes an easily implementable quality improvement measure that may decrease the rate of loss and mishandling of specimens. PMID- 26675357 TI - Unusual Cutaneous Metastasis of Uterine Carcinosarcoma: A Case Report and Review of the Literature. AB - Cutaneous metastasis of uterine cancer is rare and is often associated with late stage disease. Most uterine malignancies are endometrial adenocarcinomas, but a small subset is uterine carcinosarcoma, also known as malignant mixed Mullerian tumors. Uterine carcinosarcomas are highly aggressive tumors with an average 5 year survival rate of 26%-34%. Metastases most commonly occur in the abdominal wall, lung, and bone. Cutaneous metastasis is exceedingly rare and may pose a diagnostic challenge. The authors report a 57-year-old woman with multiple subcutaneous nodules on the face and trunk. A biopsy revealed similar morphology and staining characteristics as the sarcomatous component of the primary uterine carcinosarcoma. Histopathological features and immunophenotypical characteristics of the metastatic tumor are detailed in comparison with the original tumor. A review of the literature is also provided. PMID- 26675358 TI - Errors and mistakes in breast ultrasound diagnostics. AB - Sonomammography is often the first additional examination performed in the diagnostics of breast diseases. The development of ultrasound imaging techniques, particularly the introduction of high frequency transducers, matrix transducers, harmonic imaging and finally, elastography, influenced the improvement of breast disease diagnostics. Nevertheless, as in each imaging method, there are errors and mistakes resulting from the technical limitations of the method, breast anatomy (fibrous remodeling), insufficient sensitivity and, in particular, specificity. Errors in breast ultrasound diagnostics can be divided into impossible to be avoided and potentially possible to be reduced. In this article the most frequently made errors in ultrasound have been presented, including the ones caused by the presence of artifacts resulting from volumetric averaging in the near and far field, artifacts in cysts or in dilated lactiferous ducts (reverberations, comet tail artifacts, lateral beam artifacts), improper setting of general enhancement or time gain curve or range. Errors dependent on the examiner, resulting in the wrong BIRADS-usg classification, are divided into negative and positive errors. The sources of these errors have been listed. The methods of minimization of the number of errors made have been discussed, including the ones related to the appropriate examination technique, taking into account data from case history and the use of the greatest possible number of additional options such as: harmonic imaging, color and power Doppler and elastography. In the article examples of errors resulting from the technical conditions of the method have been presented, and those dependent on the examiner which are related to the great diversity and variation of ultrasound images of pathological breast lesions. PMID- 26675359 TI - Strand-specific RNA-seq analysis of the Lactobacillus delbrueckii subsp. bulgaricus transcriptome. AB - Lactobacillus delbrueckii subsp. bulgaricus 2038 (Lb. bulgaricus 2038) is an industrial bacterium that is used as a starter for dairy products. We proposed several hypotheses concerning its industrial features previously. Here, we utilized RNA-seq to explore the transcriptome of Lb. bulgaricus 2038 from four different growth phases under whey conditions. The most abundantly expressed genes in the four stages were mainly involved in translation (for the logarithmic stage), glycolysis (for control/lag stages), lactic acid production (all the four stages), and 10-formyl tetrahydrofolate production (for the stationary stage). The high expression of genes like d-lactate dehydrogenase was thought as a result of energy production, and consistent expression of EPS synthesis genes, the restriction-modification (RM) system and the CRISPR/Cas system were validated for explaining the advantage of this strain in yoghurt production. Several postulations, like NADPH production through GapN bypass, converting aspartate into carbon-skeleton intermediates, and formate production through degrading GTP, were proved not working under these culture conditions. The high expression of helicase genes and co-expressed amino acids/oligopeptides transporting proteins indicated that the helicase might mediate the strain obtaining nitrogen source from the environment. The transport system of Lb. bulgaricus 2038 was found to be regulated by antisense RNA, hinting the potential application of non-coding RNA in regulating lactic acid bacteria (LAB) gene expression. Our study has primarily uncovered Lb. bulgaricus 2038 transcriptome, which could gain a better understanding of the regulation system in Lb. bulgaricus and promote its industrial application. PMID- 26675360 TI - Antiviral benzofurans from Eupatorium chinense. AB - Eleven benzofuran dimers, (+)-dieupachinins A-E, (-)-dieupachinins A-E and dieupachinin F, a benzofuran trimer trieupachinin A, as well as seven known compounds were isolated from the roots of Eupatorium chinense. The enantiomers of racemates dieupachinins A-E were separated by chiral HPLC. The structures with absolute configurations were elucidated on the basis of spectroscopic data, X-ray diffraction analysis, and circular dichroism experiments. The isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus (RSV). PMID- 26675361 TI - A previously undescribed jasmonate compound in flowering Arabidopsis thaliana - The identification of cis-(+)-OPDA-Ile. AB - Jasmonates (JAs) are plant hormones that integrate external stress stimuli with physiological responses. (+)-7-iso-JA-L-Ile is the natural JA ligand of COI1, a component of a known JA receptor. The upstream JA biosynthetic precursor cis-(+) 12-oxo-phytodienoic acid (cis-(+)-OPDA) has been reported to act independently of COI1 as an essential signal in several stress-induced and developmental processes. Wound-induced increases in the endogenous levels of JA/JA-Ile are accompanied by two to tenfold increases in the concentration of OPDA, but its means of perception and metabolism are unknown. To screen for putative OPDA metabolites, vegetative tissues of flowering Arabidopsis thaliana were extracted with 25% aqueous methanol (v/v), purified by single-step reversed-phase polymer based solid-phase extraction, and analyzed by high throughput mass spectrometry. This enabled the detection and quantitation of a low abundant OPDA analog of the biologically active (+)-7-iso-JA-L-Ile in plant tissue samples. Levels of the newly identified compound and the related phytohormones JA, JA-Ile and cis-(+) OPDA were monitored in wounded leaves of flowering Arabidopsis lines (Col-0 and Ws) and compared to the levels observed in Arabidopsis mutants deficient in the biosynthesis of JA (dde2-2, opr3) and JA-Ile (jar1). The observed cis-(+)-OPDA Ile levels varied widely, raising questions concerning its role in Arabidopsis stress responses. PMID- 26675362 TI - The National Institute on Aging Health Disparities Research Framework. AB - OBJECTIVE: Development of a new framework for the National Institute on Aging (NIA) to assess progress and opportunities toward stimulating and supporting rigorous research to address health disparities. DESIGN: Portfolio review of NIA's health disparities research portfolio to evaluate NIA's progress in addressing priority health disparities areas. RESULTS: The NIA Health Disparities Research Framework highlights important factors for health disparities research related to aging, provides an organizing structure for tracking progress, stimulates opportunities to better delineate causal pathways and broadens the scope for malleable targets for intervention, aiding in our efforts to address health disparities in the aging population. CONCLUSIONS: The promise of health disparities research depends largely on scientific rigor that builds on past findings and aggressively pursues new approaches. The NIA Health Disparities Framework provides a landscape for stimulating interdisciplinary approaches, evaluating research productivity and identifying opportunities for innovative health disparities research related to aging. PMID- 26675363 TI - Heterogeneous distribution of dye-labelled biomineralizaiton proteins in calcite crystals. AB - Biominerals are highly ordered crystals mediated by organic matters especially proteins in organisms. However, how specific proteins are distributed inside biominerals are not well understood. In the present study, we use fluorescein isothiocyanate (FITC) to label extracted proteins from the shells of bivalve Pinctada fucata. By confocal laser scanning microscopy (CLSM), we observe a heterogeneous distribution of dye-labelled proteins inside synthetic calcite at the microscale. Proteins from the prismatic calcite layers accumulate at the edge of crystals while proteins from the nacreous aragonite layers accumulate at the center of crystals. Raman and X-ray powder diffraction show that both the proteins cannot alter the crystal phase. Scanning electron microscope demonstrates both proteins are able to affect the crystal morphology. This study may provide a direct approach for the visualization of protein distributions in crystals by small-molecule dye-labelled proteins as the additives in the crystallization process and improve our understanding of intracrystalline proteins distribution in biogenic calcites. PMID- 26675364 TI - Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis. AB - Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed. PMID- 26675365 TI - Weight Loss Pharmacotherapy: Brief Summary of the Clinical Literature and Comments on Racial Differences. AB - The disparity in obesity rates between White, Black, and Hispanic individuals, especially women, is striking. Moreover, at any given body mass index or abdominal girth, incident diabetes is greater in Black, Hispanic and other racial ethnic minorities than Whites. In addition to the growing health burden, the total costs of obesity in 2030 could exceed $500 billion (USD). Weight loss of 5% 15% from baseline can be attained with anti-obesity pharmacotherapy approved for long-term use in combination with lifestyle change. Weight loss of >= 5% is associated with medical benefits including reduction of incident diabetes and cardiovascular risk. While medical weight loss after one year or more in the US population is better than previously seen in many clinical trials, >60% of adults fail to sustain a 5% weight loss. Drug therapies approved for long-term weight loss may permit even more subjects to sustain healthful weight reduction. PMID- 26675366 TI - Commentary on Inhaled (239)PUO2 in Dogs - A Prophylaxis Against Lung Cancer? AB - Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from (239)PuO2 inhalation, as a prophylaxis against lung cancer. PMID- 26675367 TI - Developmental patterns of copper bioaccumulation in a marine fish model Oryzias melastigma. AB - Allometry is known to be an important factor influencing metal bioaccumulation in animals. However, it is not clear whether effects are due to body size per se or changes in physiological traits during the animals' development. We therefore investigated the biokinetics of copper (Cu) and predicted Cu bioaccumulation during the development of a fish model, the marine medaka. The results revealed that the waterborne Cu uptake rate constant decreased and dietary Cu assimilation efficiency increased during development from larvae to adults. Thus, the allometric dependency of the biokinetic parameters in juveniles and adults can not be simply extrapolated to the whole life cycle. The body Cu concentration in the fish was predicted by the biokinetic model, which showed a rapid increase in the larval stage, followed by a slight increase from juveniles to adults, and then a relatively stable plateau in the post-adult stage. Dietary Cu uptake became more important as fish developed from larvae to juveniles, but became less important from juveniles to adults. These findings suggested that the developmental patterns of metal bioaccumulation are driven by an integrated biological/physiological shift through animals' ontogeny rather than a simple allometric dependent change. The developmental changes of metal uptake should be considered in ecological bioassessment and biomonitoring programs. PMID- 26675368 TI - Titanium dioxide nanoparticles induce genotoxicity but not mutagenicity in golden mussel Limnoperna fortunei. AB - The widespread use of titanium dioxide nanoparticles (TiO2-NP) in consumer products is the cause of its appearance in wastewater and effluents, reaching the aquatic environment. The evaluation of the biological impact of TiO2-NP and the need to understand its ecotoxicological impact to the aquatic ecosystem are of major concern. Bivalve mollusks may represent a target group for nanoparticle toxicity. Limnoperna fortunei (golden mussel), a freshwater bivalve organism that has been employed in biomonitoring environmental conditions. Comet assay, micronucleus test and oxidative damage to lipids and proteins were performed after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50MUgmL(-1)). The results demonstrate that TiO2-NP can damage the DNA of haemocytes after 2h of exposure and the genotoxic activity significantly increased after 4h exposure to TiO2-NP, at all the TiO2-NP concentrations. TiO2-NP was ineffective in causing mutagenicity in the haemolymph cells of golden mussel. The increase in the lipid peroxidation levels and carbonyl proteins after the exposure to TiO2-NP indicates the induction of oxidative stress at 2h exposure with similar results to all TiO2 NP concentrations, but these effects did not occur at 4h exposure. These results demonstrated that, although TiO2-NP is not mutagenic to golden mussel, it does induce DNA damage and oxidative stress in these organisms. PMID- 26675369 TI - Sulfide exposure results in enhanced sqr transcription through upregulating the expression and activation of HSF1 in echiuran worm Urechis unicinctus. AB - Sulfide is a natural, widely distributed, poisonous substance. Sulfide: quinone oxidoreductase (SQR) is responsible for the initial oxidation of sulfide in mitochondria. To study transcriptional regulation of sqr after sulfide exposure, a 2.6-kb sqr upstream sequence from echiuran worm Urechis unicinctus was cloned by genome walking. Bioinformatics analysis showed 3 heat shock elements (HSEs) in proximal promoter region of the sqr upstream sequence. Moreover, an Hsf1 cDNA in U. unicinctus (UuHsf1) was isolated with a full-length sequence of 2334 bp and its polyclonal antibody was prepared using U. unicinctus HSF1 (UuHSF1) expressed prokaryotically with whole sequence of its open reading frame (ORF). In vivo ChIP and in vitro EMSA assays revealed UuHSF1 could interact with the sqr proximal promoter region. Transient transfection and mutation assays indicated that UuHSF1 bound specifically to HSE (-155bp to -143bp) and enhanced the transcription of sqr. Furthermore, sulfide treatment experiments demonstrated that sulfide could increase the expression of HSF1 protein, and induce trimerization of the protein which binds to HSEs and then activate sqr transcription. Quantitative real-time PCR analysis revealed sqr mRNA level increased significantly after U. unicinctus was exposed to sulfide for 6h, which corresponded to content changes of both trimeric HSF1 and HSF1-HSE complex. We concluded that UuHSF1 is a transcription factor of sqr and sulfide could induce sqr transcription by upregulating the expression and activation of HSF1 in U. unicinctus exposed to sulfide. PMID- 26675370 TI - Stability evaluation of reference genes for real-time PCR in zebrafish (Danio rerio) exposed to cadmium chloride and subsequently infected by bacteria Aeromonas hydrophila. AB - Environmental and occupational cadmium (Cd) toxicity is a global concern, and the model organism zebrafish is an ideal species to investigate Cd toxicity. Among various detecting techniques, quantitative real-time PCR (qPCR) is a sensitive and efficient tool. Stable reference genes are critical for relative qPCR analysis. However, accumulated evidence shows that conventional reference genes can vary significantly under different experimental setups. Here we evaluated the stability of eight candidate reference genes of zebrafish with or without exposure to different concentrations of Cd. The results showed that the best four suitable reference genes in the five selected organs were: (1) spleen: beta actin>gapdh>ef1alpha>rpl13alpha; (2) kidney: rplp2>rpl7>beta-actin>ef1alpha; (3) liver: rpl7>rpl13alpha>beta-actin>ef1alpha; (4) gills: rplp2>gapdh>rnf7>ef1alpha; (5) intestine: ef1alpha>rnf7>rplp2>rpl13alpha. Moreover, we further assessed the expression stability of the four reference genes for Cd immunotoxicology studies in zebrafish. The expression profiles showed that ef1alpha in spleen and kidney, rpl13a in liver and rplp2 in intestine were the most suitable reference genes at 12h and 9 days after the injection with Aeromonas hydrophila following Cd exposure. In gills, the expression of gapdh was more stable than ef1alpha after 9 days of bacteria challenge while ef1alpha showed a higher stability than gapdh at 12h after bacteria injection. In conclusion, this study has demonstrated that different tissues of zebrafish have different suitable reference genes after Cd exposure and the subsequently pathogenic insults for qPCR. It emphasized the importance of reference gene evaluation for studies using qPCR, in particular when investigations involve factors not explored previously. PMID- 26675371 TI - Different physiological and photosynthetic responses of three cyanobacterial strains to light and zinc. AB - Zinc pollution of freshwater aquatic ecosystems is a problem in many countries, although its specific effects on phytoplankton may be influenced by other environmental factors. Light intensity varies continuously under natural conditions depending on the cloud cover and the season, and the response mechanisms of cyanobacteria to high zinc stress under different light conditions are not yet well understood. We investigated the effects of high zinc concentrations on three cyanobacterial strains (Microcystis aeruginosa CPCC299, M. aeruginosa CPCC632, and Synechocystis sp. FACHB898) grown under two light regimes. Under high light condition (HL), the three cyanobacterial strains increased their Car/Chl a ratios and non-photochemical quenching (NPQ), with CPCC299 showing the highest growth rate-suggesting a greater ability to adapt to those conditions as compared to the other two strains. Under high zinc concentrations the values of maximal (FM) and operational (F'M) photosystem II quantum yields, photosystem I quantum yield [Y(I)], and NPQ decreased. The following order of sensitivity to high zinc was established for the three strains studied: CPCC299>CPCC632>FACHB898. These different sensitivities can be partly explained by the higher internal zinc content observed in CPCC299 as compared to the other two strains. HL increased cellular zinc content and therefore increased zinc toxicity in both M. aeruginosa strains, although to a greater extent in CPCC299 than in CPCC632. Car/Chl a ratios decreased with high zinc concentrations under HL only in CPCC299, but not under low light (LL) conditions for all the studied strains, suggesting that the three strains have different response mechanisms to high zinc stress when grown under different light regimes. We demonstrated that interactions between light intensity and zinc need to be considered when studying the bloom dynamics of cyanobacteria in freshwater ecosystems. PMID- 26675372 TI - Do plastic particles affect microalgal photosynthesis and growth? AB - The unbridled increase in plastic pollution of the world's oceans raises concerns about potential effects these materials may have on microalgae, which are primary producers at the basis of the food chain and a major global source of oxygen. Our current understanding about the potential modes and mechanisms of toxic action that plastic particles exert on microalgae is extremely limited. How effects might vary with particle size and the physico-chemical properties of the specific plastic material in question are equally unelucidated, but may hold clues to how toxicity, if observed, is exerted. In this study we selected polystyrene particles, both negatively charged and uncharged, and three different sizes (0.05, 0.5 and 6MUm) for testing the effects of size and material properties. Microalgae were exposed to different polystyrene particle sizes and surface charges for 72h. Effects on microalgal photosynthesis and growth were determined by pulse amplitude modulation fluorometry and flow cytometry, respectively. None of the treatments tested in these experiments had an effect on microalgal photosynthesis. Microalgal growth was negatively affected (up to 45%) by uncharged polystyrene particles, but only at high concentrations (250mg/L). Additionally, these adverse effects were demonstrated to increase with decreasing particle size. PMID- 26675373 TI - Sonography of iatrogenic pneumothorax in pediatric patients. AB - Pneumothorax is defined as the presence of air in the pleural cavity. The incidence of iatrogenic pneumothorax in the pediatric population is 0.3-0.48 in 1000 patients. A conventional chest X-ray, in some cases supplemented with chest computed tomography, is a typical imaging examination used to confirm the diagnosis of pneumothorax. Within the last years, the relevance of transthoracic lung ultrasound in the diagnostic process of this disease entity has greatly increased. This is confirmed by the opinion of a group of experts in ultrasound lung imaging in patients in a life-threatening condition, who strongly recommend a transthoracic ultrasound examination for the diagnosis of pneumothorax in such patients. These data constituted the basis for initiating the prospective studies on the application of this method in pneumothorax diagnosis in patients of pediatric hematology and oncology wards. AIM: The aim of the study was to present the possibility of using the transthoracic lung ultrasound in the diagnostic process of pneumothorax in pediatric patients, with particular attention paid to its iatrogenic form. The article discusses sonographic criteria for pneumothorax diagnosis in pediatric patients, including the sensitivity and specificity of the method, in relation to conventional chest X-ray. MATERIAL AND METHODS: The prospective studies included a group of patients treated in the Clinic of Pediatrics, Pediatric Hematology, Oncology and Endocrinology of the Academic Clinical Centre (Medical University of Gdansk, Poland) in whom a central venous catheter was placed in the subclavian veins. The studies lasted for one year - from 1 July 2011 to 30 June 2012. The examined group comprised 63 patients - 25 girls (39.7%) and 38 boys (60.3%) aged from 1 to 17. The analysis included the results of 115 ultrasound examinations conducted in this group. RESULTS: In t he examined group with suspected or diagnosed neoplasm, iatrogenic pneumothorax was identified in 4 out of 63 patients (6.3%). In all cases, it was a consequence of procedures connected with the introduction of a central catheter. In the examined material, the sensitivity, specificity and predictive values (positive and negative) of the transthoracic lung ultrasound equaled 100%. CONCLUSIONS: The transthoracic ultrasound examination is a highly effective method in diagnosing iatrogenic pneumothorax in pediatric patients. However, to confirm this conclusion, multicenter studies, among considerably larger populations, are necessary. PMID- 26675375 TI - Assessing the impacts of the first year of rotavirus vaccination in the United Kingdom. AB - The United Kingdom (UK) added rotavirus (RV) vaccine (Rotarix GlaxoSmithKline) to the national vaccine schedule in July 2013. During the 2012-2014 rotavirus seasons, children presenting to the Bristol Royal Hospital for Children Emergency Department with gastroenteritis symptoms had stool virology analysis (real-time PCR) and clinical outcome recorded. Nosocomial cases were identified as patients with non-gastroenteritis diagnosis testing positive for rotavirus > 48h after admission. In comparison to average pre-vaccine seasons, in the first year after vaccine introduction there were 48% fewer attendances diagnosed with gastroenteritis, 53% reduction in gastroenteritis admissions and a total saving of 330 bed-days occupancy. There was an overall reduction in number of rotavirus positive stool samples with 94% reduction in children aged under one year and a 65% reduction in those too old to have been vaccinated. In the first year after the introduction of universal vaccination against rotavirus we observed a profound reduction in gastroenteritis presentations and admissions with a substantial possible herd effect seen in older children. Extrapolating these findings to the UK population we estimate secondary healthcare savings in the first year of ca L7.5 (?10.5) million. Ongoing surveillance will be required to determine the long-term impact of the RV immunisation programme. PMID- 26675374 TI - Are Korean Patients Different from Other Ethnic Groups in Total Knee Arthroplasty? AB - Most of the implants used for total knee arthroplasty (TKA) in Asian patients have been produced based on anthropometry of Western people. Since anatomic features and life styles are different between Western and Eastern people, there would be ethnic differences in terms of conformity of implants to the patient's anatomy or clinical results after TKA. Therefore, surgeons in Asia are particularly interested in related surgical techniques and implant designs used in TKA for improved clinical results and patient satisfaction. In this review, we investigated the anthropometric differences of Koreans from Westerners. Koreans are of shorter stature, less weight, and smaller skeletal structure and have a higher incidence of constitutional varus alignment of the lower extremity. Moreover, compared to Westerner TKA populations, the proportion of female patients was large and primary osteoarthritis was prevalent in preoperative diagnosis in Korean TKA patients. Culturally, Koreans have life styles that demand high flexion positions of the knee such as squatting, kneeling, and cross legged sitting. Although there were no notable differences in the complication and revision rates following TKA between Westerners and Koreans, the incidence of postoperative deep vein thrombosis and pulmonary thromboembolism was lower in Koreans than Westerners. We hope that further research on implant designs and more interest in TKA will improve outcomes in Korean patients. PMID- 26675376 TI - Analysis of risk and predictors of brain radiation necrosis after radiosurgery. AB - In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892+/-0.0335, 0.650+/-0.0717, and 0.712+/-0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold. PMID- 26675377 TI - GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1. AB - GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2's potential for a new therapeutic approach for treating HIV-1. PMID- 26675378 TI - Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors. AB - Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors. Herein, we provide a comprehensive study of NAPRT and NAMPT expression across human tissues and tumor cell lines. We show that both genes are widely expressed under normal conditions and describe the occurrence of novel NAPRT transcripts. Also, we explore some of the NAPRT gene expression mechanisms. Our findings underline that the efficiency of NA in treatments with NAMPT inhibitors is dependent on the knowledge of the expression profiles and regulation of both NAMPT and NAPRT. PMID- 26675380 TI - The total cost of rearing a heifer on Dutch dairy farms: calculated versus perceived cost. AB - BACKGROUND: As farmers do not often keep a record of the expenditures for rearing, an economic tool that provides insight into the cost of rearing is useful. In the Netherlands, an economic tool (Jonkos) has been developed that can be used by farmers to obtain insight into the cost of rearing on their farm. The first objective of this study is to calculate the total cost of rearing young stock in Dutch dairy herds using Jonkos. The second objective is to compare the calculated total cost of rearing with the farmers' own estimation of the cost of rearing (the perceived cost). FINDINGS: Information was available for 75 herds that reared their own young stock and who had used the Jonkos tool. The perceived cost of rearing young stock was only available for 36 herds. In the 75 herds, the average herd size was 100 dairy cows. The average calculated total cost of rearing a heifer was ?1,790. The average perceived total cost of rearing a heifer (including labour and housing costs) was ?1,030. CONCLUSION: Most Dutch farmers in the study underestimated the total cost of rearing. The Jonkos economic tool has the advantage that herd-specific information can be entered as input values. The output of the tool can improve the awareness of farmers about the total costs of rearing. This awareness can lead to a higher priority of young stock rearing and consequently to an improved quality of young stock rearing. PMID- 26675379 TI - Advanced endoscopic imaging of indeterminate biliary strictures. AB - Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs. PMID- 26675381 TI - Laparoscopic ablation therapies or hepatic resection in cirrhotic patients with small hepatocellular carcinoma. AB - BACKGROUND: The Barcelona Clinic Liver Cancer staging system recommends radiofrequency ablation as treatment of choice for patients with "small" (up to 2 cm in size) hepatocellular carcinoma. AIMS: Aim of the study was to assess whether laparoscopic ablation therapies or hepatic resection could be proposed as alternative option if percutaneous approach is not feasible. METHODS: Overall survival and tumour recurrence rate were compared in a retrospective cohort of 176 consecutive patients with small hepatocellular carcinoma on cirrhosis treated by laparoscopic ablation therapies or surgery. To balance the covariates between the two groups, a propensity case-matched analysis was developed to generate a matched sample, which included 76 patients in each arm. RESULTS: Local tumour progression (p=0.005), intra-segmental recurrence (p=0.0001), and 5-year recurrence rates (80% vs. 60%; p=0.0014) were significantly higher in the ablation therapies group. The 5-year survival rate were 48% after ablation therapies and 69% after hepatic resection (p=0.0006). Multivariate analysis showed that MELD score, alpha-fetoprotein value, procedure category and intraoperative restaging were associated with survival, while the surgery was the only independent predictor of intra-hepatic recurrence. CONCLUSIONS: The present study suggests that, if percutaneous ablation is not feasible, hepatic resection may be considered as a sound option in the treatment of small hepatocellular carcinoma. PMID- 26675382 TI - Evidence for partial pharmaceutical reversal of the cancer anorexia-cachexia syndrome: the case of anamorelin. AB - A major component of the cancer anorexia-cachexia syndrome is a decline in food intake. Up until now none of the drugs that improve appetite also improve skeletal muscle. Recent studies have suggested that the oral ghrelin-analog, anamorelin, increased food intake and muscle mass. Unfortunately, it does not increase muscle power. Its regulatory future is uncertain, although it has important clinical effects. PMID- 26675383 TI - Sutureless and Glue-free Versus Sutures for Limbal Conjunctival Autografting in Primary Pterygium Surgery: A Prospective Comparative Study. AB - INTRODUCTION: Sutureless and glue-free conjunctival autograft as a treatment modality for primary pterygium is recently gaining popularity but conventional technique of suturing conjunctival autograft is still practised widely. AIM: To compare the outcome of sutureless and glue-free technique with sutures for limbal conjunctival autografting in management of primary pterygium. MATERIALS AND METHODS: A prospective interventional study was carried out in 50 consecutive eyes with primary nasal pterygium requiring surgical excision. Simple excision under local anaesthesia was performed followed by closure of the bare sclera by sutureless and glue-free conjunctival autograft in 25 eyes of 25 patients (group 1) and by the conventional method of suturing conjunctival autograft using interrupted 10-0 nylon sutures in 25 eyes of 25 patients (group 2), followed by bandaging for 24 hours in both the groups. Surgical time was recorded for both the techniques. Postoperative discomfort was assessed using preformed questionnaires. The patients were followed up for 6 months. During follow up, graft related complications and recurrence if any were noted. RESULTS: Mean surgical time for group 1 (23.20+/-1.55 minutes) was significantly less as compared to group 2 (37.76+/-1.89 minutes); (p=0.001). Postoperative symptoms were seen in less number of patients (20%) and were of shorter duration (2 weeks) in group 1 as compared to group 2 with 20 (80%) patients having symptoms lasting for 4 weeks; (p<0.001). Recurrence rate and conjunctival granuloma formation rate for group 1 (0%) and for group 2 (4%) were statistically insignificant. CONCLUSION: Sutureless and glue-free conjunctival autograft technique is simple, easy, safe, effective and less time consuming than sutured limbal autograft technique with less postoperative discomfort and adverse events encountered with the use of suture material. Postoperative results of both techniques are comparable. Hence sutureless and glue-free conjunctival autografting is a good technique for the treatment of primary pterygium. PMID- 26675385 TI - New aspects in shear-wave elastography of prostate cancer. AB - AIM: This study was designed to evaluate the performance of shear-wave elastography as a diagnostic tool for prostate cancer in a larger cohort of patients than previously reported. PATIENTS AND METHODS: Seventy-three patients with suspected prostate carcinoma were investigated by ultrasound elastography followed by directed biopsy. The elastographic and histological results for all biopsies were compared. RESULTS: After exclusion of invalid and non-assessable results, 794 samples were obtained for which both a histological assessment and an elastometric result (tissue stiffness in kPa) were available: according to the histology 589 were benign and 205 were malignant. Tissue elasticity was found to be weakly correlated with patient's age, PSA level and gland volume. ROC analysis showed that, for the set of results acquired, elastometry did not fulfil literature claims that it could identify malignant neoplasia with high sensitivity and specificity. However, it did show promise in distinguishing between Gleason scores <=6 and >6 when malignancy had already been identified. Unexpected observations were the finding of a smaller proportion of tumours in the lateral regions of the prostate than generally expected, and also the observation that the elasticity of benign prostate tissue is region-sensitive, the tissue being stiffest in the basal region and more elastic at the apex. CONCLUSIONS: Shear-wave elastography was found to be a poor predictor of malignancy, but for malignant lesions an elasticity cut-off of 80 kPa allowed a fairly reliable distinction between lesions with Gleason <=6 and those with Gleason >6. We demonstrate an increase in elasticity of benign prostate tissue from the basal to the apical region. PMID- 26675386 TI - Ultrasound image of the skin, apparatus and imaging basics. AB - Ultrasound imaging of the skin is becoming more and more popular. Skin ultrasound examinations are used both in order to assess healthy skin and to evaluate pathological lesions. They are mainly performed in dermatology as well as in broadly understood aesthetic medicine and cosmetology. At present, skin imaging is enabled by high-frequency equipment and high-quality conventional devices. The introduction of high-frequency electronic transducers which are supported by conventional scanners may be a turning point in skin ultrasound equipment. Irrespective of the ultrasound scanner, three layers may be distinguished in the image of the healthy skin: epidermal echo, dermis and subcutaneous tissue. High frequency equipment allows for detailed imaging of the epidermal echo, dermis and upper part of the subcutaneous tissue. It is also possible to visualize the skin appendages (hair with follicles and nails) as well as slight vessels that run in the dermis and upper subcutaneous tissue. Contrary to high-frequency equipment, conventional scanners do not allow for a detailed assessment of the epidermal and dermal echoes. Instead, they enable the visualization of the entire subcutaneous tissue. The following parameters are used for the assessment of skin ultrasound images: thickness of individual skin layers, caliber of blood vessels, echogenicity of the dermis or its individual layers, echogenicity of the subcutaneous tissue as well as the presence or absence of flow in slight venous vessels. Currently, the studies on the usage of sonoelastography for skin assessment are in progress. Considering the dynamic development of skin imaging equipment and its diagnostic possibilities, one might suspect that high-frequency examinations will become more common and will be fundamental for the evaluation of both healthy and pathologically altered skin. This paper is an introduction to a series of articles on the clinical application of high-frequency ultrasound. The next articles will be published in the subsequent issues. PMID- 26675384 TI - H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes. AB - Establishing and maintaining cell identity depends on the proper regulation of gene expression, as specified by transcription factors and reinforced by epigenetic mechanisms. Among the epigenetic mechanisms, heterochromatin formation is crucial for the preservation of genome stability and the cell type-specific silencing of genes. The heterochromatin-associated histone mark H3K9me3, although traditionally associated with the noncoding portions of the genome, has emerged as a key player in repressing lineage-inappropriate genes and shielding them from activation by transcription factors. Here we describe the role of H3K9me3 heterochromatin in impeding the reprogramming of cell identity and the mechanisms by which H3K9me3 is reorganized during development and cell fate determination. PMID- 26675387 TI - Reply. PMID- 26675388 TI - [Guildeline for twin pregnancies (part 2): diagnosis and management for complicated twins]. PMID- 26675389 TI - [Chinese expert consensus on definition and nomenclature of female genital tract congenital anomalies]. PMID- 26675391 TI - [Impact of area under the curve of oral glucose tolerance test on pregnant woman with gestational diabetes mellitus]. AB - OBJECTIVE: To investigate whether area under the curve (AUC) of oral glucose tolerance test (OGTT) could work as a predictor of outcomes of gestational diabetes mellitus (GDM) on condition that blood glucose is controlled. METHODS: A total of 1 796 women who had a standard antenatal care in Peking University First Hospital and gave single live births from July 1, 2011 to December 31, 2 013 were included. They should be diagnosed of GDM by the diagnosis criteria of gestational diabetes published by the Ministry of Health of PRC and diabetes pre pregnancy excluded. Data were analyzed with SPSS 17.0, grouping by AUC. RESULTS: (1) Women with higher AUC had a rising trend of age and a downward trend of gestational weight gain, however, not statistically significant [specifically, in the four group of less than 15.00 mmol . L-1 . h-1, 15.00 to 16.79 mmol . L-1 . h 1, 16.80 to 17.99 mmol . L-1 . h-1 and 18.00 mmol . L-1 . h-1 or more, gestational weight gain was (15.3 +/- 5.2), (14.1 +/- 4.8), (13.5 +/- 4.7) and (13.1 +/- 4.8) kg]. The prevalence of macrosomia raised while AUC increased. Those with an AUC of lower than 15.00 (mmol . L-1 . h-1) had a lower risk of macrosomia (P = 0.04). But those with an AUC of 18.00 (mmol . L-1 . h-1) or more had a higher risk of macrosomia (P = 0.02). There was a rising trend in premature birth and preeclampsia with AUC increasing but not significant (the prevalence of premature birth was 4.38%, 5.36%, 7.71% and 7.94% while that of preeclampsia was 2.85%, 4.69%, 4.67% and 5.08% in these four groups). (2) The prevalence of macrosomia was 12.76% (54/423) when overweight pre-pregnancy, significantly higher compared with 5.87% (65/1 107) in normal group. The prevalence of preeclampsia was 5.91% (25/423) and 3.34% (37/1 107) in those two groups, which was also significantly different. The obese group had a statistically highest prevalence of preeclampsia of 9.23% (12/130). (3) AUC (P < 0.05, OR = 1.113, 95% CI: 1.008-1.218), as well as gestational weight gain (P < 0.05, OR = 1.520, 95% CI: 1.279-1.806) and pre-pregnancy BMI (P < 0.05, OR = 1.183, 95% CI: 1.125 1.243) made a difference in the prevalence of macrosomia. Meanwhile, pre pregnancy BMI made sense in the prevalence of premature labor (P < 0.05, OR = 1.059, 95% CI: 1.003-1.119) and preeclampsia (P < 0.01, OR = 1.202, 95% CI: 1.123 1.286). CONCLUSIONS: AUC, as well as pre-pregnancy BMI and gestational weight gain have a significant impact on outcomes of GDM, macrosomia especially, though blood glucose is controlled. Meanwhile, AUC might be considered as a predictor of macrosomia. PMID- 26675390 TI - [Effect of the treatment acceptance on the perinatal outcomes in women with subclinical hypothyroidism, positive thyroid gland peroxidase antibody in early pregnancy]. AB - OBJECTIVE: To investigate if women with subclinical hypothyroidism (SCH), positive thyroid gland peroxidase antibody (TPOAb) in early pregnancy accepted treatment or not had effect on perinatal outcomes. METHODS: 15 000 pregnant women who delivered in Women and Infants Hospital of Zhengzhou from January 1, 2013 to June 30, 2014 were recruited retrospectively. Among them, 2 042 women had SCH in early pregnancy. The diagnostic standard of SCH was serum free thyroxine (FT4) between 12.91-22.35 pmol/L and TSH level between 5.22-10.00 mU/L. TPOAb level >= 34 U/L was defined as positive result. The 2 042 patients with SCH were divided into the treated group (1 236 cases) and the untreated group (806 cases), according to whether or not women accepted the levothyroxine treatment. Meanwhile, the 2 042 patients with SCH were divided into the TPOAb (+) treated group (1 021 cases), the TPOAb (+) untreated group (201 cases), the TPOAb (-) treated group (215 cases) and the TPOAb (-) untreated group (605 cases), according to the TPOAb result and acceptance the levothyroxine treatment. 2 000 pregnant women with normal thyroid function who delivered in the same period were selected as the control group. Perinatal outcomes were analyzed. RESULTS: (1) The incidence of SCH in early pregnancy was 13.61% (2 042/15 000). 60.53% (1 236/2 042) accepted levothyroxine treatment and 39.47% (806/2 042) did not. (2) The incidence of abortion (5.71%, 46/806), premature delivery (6.20%, 50/806), gestational hypertension disease (13.90%, 112/806), gestational diabetes mellitus (GDM; 6.58%, 53/806), fetal growth restriction (FGR; 12.28%, 99/806) and low birth weight infants (10.17%, 82/806) in the untreated group were higher than those in the treated group [3.96% (49/1 236), 4.21% (52/1 236), 10.76% (133/1 236), 4.13% (51/1 236), 8.90% (110/1 236), 7.52% (93/1 236), respectively] and the control group [3.60% (72/2 000), 4.00% (80/2 000), 10.70% (214/2 000), 3.80% (76/2 000), 9.60% (192/2 000), 7.50% (150/2 000), respectively]. The differences were statistically significant (P < 0.05). While there was no statistically significant difference in the incidence of placental abruption, anemia in pregnant women, or fetal distress among the three groups (P > 0.05). (3)The incidences of abortion (11.44%, 23/201), premature delivery (12.44%, 25/201), gestational hypertension disease (22.89%, 46/201), GDM (8.46%, 17/201), FGR (19.90%, 40/201) and low birth weight infants (16.42%, 33/201) in the TPOAb (+) untreated group were higher than those in TPOAb (+) treated group [4.02% (41/1 021), 4.21% (43/1 021), 10.77% (110/1 021), 4.11% (42/1 021), 8.72% (89/1 021), 7.35% (75/1 021), respectively] and the control group, with statistically significant differences (P < 0.05). The incidence of the pregnancy complications in the TPOAb (+) treated group was higher than those in the control group, but the differences were not statistically significant (P > 0.05). (4) There were no statistically significant difference (P > 0.05) in the incidence of abortion (3.72%, 8/215), premature delivery (4.19%, 9/215), gestational hypertension disease (10.70%, 23/215), GDM (4.19%, 9/215), FGR (9.77%, 21/215) or low birth weight infants (8.37%, 18/215) among the TPOAb (-) treated group, the TPOAb (-) untreated group [3.80% (23/605), 4.13% (25/605), 10.91% (66/605), 5.95% (36/605), 9.75% (59/605), 8.10% (49/605), respectively] and the control group. CONCLUSIONS: (1) The incidence of abortion, premature delivery, gestational hypertension disease, GDM, FGR and low birth weight infants could be increased in women with SCH in early pregnancy. (2) Thyroxine treatment could reduce the incidence of pregnancy complications in women with SCH in early pregnancy. PMID- 26675392 TI - [Relevance between expectations before treatment, new symptoms and satisfaction after treatment in patients with pelvic organ prolapse]. AB - OBJECTIVE: To investigate the relevance between expectations before treatment, new symptoms and satisfaction after treatment of the pelvic organ prolapse (POP) patients. METHODS: Made a collection of 75 cases of POP patients at Peking University Third Hospital, who were affected by the POP symptoms and came to our clinic for treatment from January to December in 2013. Prospectively investigate the patients' expectations before treatment, which were the most troubling symptoms to be solved. According to treatment we divided the patients into surgery and pessary groups. Two groups were followed up with the degree to achieve the desired goals using patient global impression of improvement (PGI-I), new symptoms and satisfaction after treatment, try to find the relevance between expectations before treatment, new symptoms and satisfaction after treatment. RESULTS: There were 47 (63%, 47/75) patients in the surgical group and 28 (37%, 28/75) patients in the pessary group. The top three problems for patients were friction when walking (25%, 19/75), dysuria (23%, 17/75) and the feeling of vaginal prolapse (19%, 14/75). The follow-up rate was of 93% (70/75), follow-up time was (5 +/- 4) months. Satisfaction score after treatment of surgical group was higher than that of pessary group [(4.9 +/- 0.4) versus (4.0 +/- 1.3) scores, P < 0.01]. There was no statistically significant difference between two groups of PGI-I score [(6.7 +/- 0.6) versus (6.6 +/- 0.9) scores, P = 0.886]. The top three new symptoms after treatment were increased secretion, urinary incontinence and dysuria. PGI-I and satisfaction scores was relevant (P = 0.021). The availability of new symptoms and satisfaction scores was relevant (P = 0.001). CONCLUSION: When achieving higher expectations to the treatment and no more new symptoms, the satisfaction score after treatment is higher. PMID- 26675393 TI - [Study on morphological characteristics of uterosacral and cardinal ligament in patients with severe pelvic organ prolapse based on MRI]. AB - OBJECTIVE: To evaluate morphological structure of uterosacral ligament (USL) and cardinal ligament (CL) in patients with severe pelvic organ prolapse (POP) by MRI technology, and to analysis and discuss its clinical significance. METHODS: From November 2013 to February 2014 in Peking University People's Hospital, 26 elderly patients with III-IV degree of POP were selected as the POP group and 18 healthy elderly volunteers were selected as the control group during the same period. Pelvic MRI examination were performed in the two groups. The morphological characteristics of left and right side of the uterosacral-cardinal ligament on MRI and the attachment site of the starting and ending points between two group were described and compared. RESULTS: In POP group, 25 cases of left USL starting point were located in the sacrospinous ligament/coccygeal muscle complex [58% (15/26)] or coccygeal muscle [38% (10/26)], ending point were located in the cervix and vagina [58% (15/26)] or cervix [38% (10/26)]; 24 cases of right USL starting point were located in the sacrospinous ligament/coccygeal muscle complex [31% (8/26)] or coccygeal muscle [62% (16/26)], 26 cases of right USL ending point were located in the cervix and vagina [62% (16/26)] or cervix [38% (10/26)]; the left and right CL in the POP group and the control group were both from the sacroiliac joint at the top of the greater sciatic foramen from the ipsilateral pelvic side wall; 1 case (4%, 1/26) of left CL in the POP group completely connected to the bladder, 10 cases (38%, 10/26) partly connected to the bladder; 14 cases (54%, 14/26) of right CL partly connected to the bladder, the rest ending points of left and right CL were located in cervix and (or) vagina. In the control group, 17 cases of left USL starting point were located in the sacrospinous ligament/coccygeal muscle complex (10/18) or coccygeal muscle (7/18), ending point were located in the cervix and vagina (12/18) or cervix (6/18); 18 cases of right USL starting point were located in the sacrospinous ligament/coccygeal muscle complex (10/18) or coccygeal muscle (8/18), ending point were located in the cervix and vagina (13/18) or cervix (5/18); 8 cases (8/18) of left CL partly connected to the bladder; 15 cases (15/18) of right CL partly connected to the bladder, the rest ending points of left and right CL were located in cervix and (or) vagina. There was no significant difference between the two groups on the starting and ending points (P > 0.05). CONCLUSIONS: The observation of MRI could be consistent with the clinical anatomy on the starting and ending points, direction of travel in the uterosacral-cardinal ligament. The starting and ending points of the left and right side USL and the ending points of the left and right side CL are not completely symmetrical, the variation degree is large, some CL could be completely or partly inserted to the bladder. PMID- 26675394 TI - [Evidence of perineural invasion on early-stage cervical cancer and prognostic significance]. AB - OBJECTIVE: To evaluate the incidence and significance of perineural invasion (PNI) in cervical cancer. METHODS: Retrospective chart review of patients with cervical cancer (stages Ia2-IIb) who underwent radical hysterectomy and pelvic lymphadenectomy from 2007 to 2012. To evaluate the incidence and significance of PNI in cervical and uterine tissues by microscopic examination. RESULTS: A total of 238 patients were included, 9.2% (22/238) patients with PNI in the cervical stroma. Patients with PNI were more likely to have adverse histopathologic features, including lymphoma vascular space invasion, parametrical invasion, depth of invasion, tomor size and lymph nodes metastases (all P < 0.05). PNI were independent of age, international federation of gynecology and obstetrics (FIGO) stage, histopathology type and grade, and positive vaginal margin (all P > 0.05). Patients with PNI had shorter disease-free and overall survival (P = 0.002 and P = 0.008, respectively). On multivariate analysis, risk factors for recurrence and death included parametrical invasion and depth of invasion (P < 0.05). Similarly, risk factors for recurrence included lymph nodes metastases (P = 0.024). However, PNI was not identified as an independent risk factor for either recurrence or death (P > 0.05). CONCLUSIONS: PNI exists in early cervical cancer. PNI is associated with tumor size, depth of invasion, parametrical invasion, lymphoma vascular space invasion and lymph nodes metastases. PNI represente a decreasing disease-free and overall survival in patients with early-stage cervical cancer, and is independently associated with multiple high-risk factors, which be informed management decisions regarding adjuvant therapy. PMID- 26675395 TI - [Protein levels and its clinical significance of septin-9 and clusterin in peripheral blood of epithelial ovarian cancer patients]. AB - OBJECTIVE: To evaluate septin-9 and clusterin protein levels in the peripheral blood samples from epithelial ovarian cancer patients, and explore its clinical significance. METHODS: Clinical data of 200 patients in Cancer Hospital, Chinese Academy of Medical Sciences from Jan. 29, 2008 to Feb. 1, 2010 were collected. The peripheral blood samples were obtained from 137 epithelial ovarian cancer patients, 12 borderline ovarian tumor patients, 10 benign ovarian tumor patients, 41 benign pelvic lesion patients and 58 healthy women. The septin-9 and clusterin protein levels in the plasma were measured by double antibody sandwich ELISA or ELISA. The clinical significance of clusterin and septin-9 in plasma was analyzed. The diagnostic efficacy of septin-9 and clusterin protein in the detection of ovarian cancer was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Double antibody sandwich ELISA showed: the mean levels of plasma septin-9 in epithelial ovarian cancer patients or benign pelvic lesion patients were significantly higher than that in healthy women detedted by double antibody sandwich ELISA (P < 0.01). The mean levels of plasma septin-9 in epithelial ovarian carcinoma patients with tumor family history or distance metastasis were significantly higher than those patients without (P < 0.05). While the expression level of septin-9 protein in peripheral blood of ovarian cancer patients was not related to the patient age, pathologic stage, pathologic differentiation, smoking history, treatment history (including surgery, radiotherapy and chemotherapy) and lymph node metastasis (all P > 0.05). ELISA showed: the mean level of plasma clusterin in epithelial ovarian cancer patients was significantly higher than that in healthy women deteded by ELISA (P = 0.021). The expression level of clusterin protein in peripheral blood of ovarian cancer patients was not related to the above clinical pathological parameters (all P > 0.05). To distinguish between ovarian cancer patients and healthy women by septin-9 protein expression level in plasma, when AUC was 0.712 and cut off was 0.28, the sensitivity of detection ovarian cancer by septin-9 protein expression was 82.5%, and the specificity was 50.0%. To distinguish between ovarian cancer patients and healthy women by clusterin protein expression level in plasma, when AUC was 0.636 and cut off was 87.96 pg/L, the sensitivity of detection ovarian cancer by clusterin protein expression was 71.5%, and the specificity was 41.4%. CONCLUSIONS: The expression of septin-9 and clusterin protein in peripheral blood of ovarian cancer patients is increased, especially the expression level of septin-9 protein with related to the distant metastasis. The study results shown that the detection of septin-9 and clusterin in plasma has a certain diagnosis value in ovarian cancer, which may be a potential markers for ovarian cancer. PMID- 26675396 TI - [Research of the influence and mechanism about metformin on the proliferation of differentiated endometrial carcinoma cells]. AB - OBJECTIVE: To investigate the effects of metformin on cell proliferation in differentiation degree of endometrial carcinoma cells and related mechanisms. METHODS: The endometrial cancer cell lines Ishikawa and AN3CA were used. Cell proliferation was assessed after exposure to metformin with or without epithelial growth factor receptor (EGFR) inhibitor AG1478 by cell counting kit-8 (CCK-8) method. EGFR mRNA was determined by reverse transcription (RT)-PCR. The expression of phosphorylation EGFR (p-EGFR) and total EGFR (t-EGFR) and phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) were examined by western blot. RESULTS: (1) CCK-8 experiment showed that metformin could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and a dose-dependent manner (P < 0.05), but the inhibition of well differentiated cell line Ishikawa was lower than that in poorly differentiated cells AN3CA (P < 0.05). AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P < 0.05), but the inhibition rate of well differentiated cell line Ishikawa was higher than that in poorly differentiated cells AN3CA (P < 0.05). Metformin + AG1478 also could inhibit the proliferation of endometrial cancer cells in a time-dependent manner and in a dose-dependent manner (P < 0.05), and the inhibition of combined with metformin and AG1478 was stronger than that with a single application of drugs, but the inhibition rate of Ishikawa was higher than that in AN3CA (P < 0.05). (2) RT-PCR method showed that different concentrations of metformin (0.01, 0.1, 1, 5, 10 mmol/L, respectively) for 24 hours, the expression level of EGFR mRNA in Ishikawa cells were respectively 0.74 +/- 0.03, 0.61 +/- 0.04, 0.46 +/- 0.03, 0.31 +/- 0.03 and 0.23 +/- 0.03, the expression level of EGFR mRNA in AN3CA cells were respectively 0.79 +/- 0.20, 0.61 +/- 0.03, 0.50 +/- 0.05, 0.32 +/- 0.03 and 0.26 +/- 0.04, the inhibition effect showed a significant concentration-dependent manner (all P < 0.01). (3) Western blot method displayed that the effect of metformin treated respectively 2, 4, 6 or 8 hours, there were not significant difference in the expression levels of t-EGFR protein and t-ERK1/2 between Ishikawa and AN3CA cells (all P > 0.05). But the expression levels of p-EGFR and p-ERK1/2 protein were significantly lower between two groups (P < 0.01), which showed a time-dependent manner (P < 0.01). CONCLUSION: Metformin could inhibit the proliferation of endometrial cancer cells, the inhibition is associated with the differentiation degree of cancer cells. Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells. PMID- 26675397 TI - Aberrant Gene Expression Profile of Unaffected Colon Mucosa from Patients with Unifocal Colon Polyp. AB - BACKGROUND The aim of this study was to evaluate gene expression profiles in unaffected colon mucosa and polyp tissue from patients with unifocal colon polyp to investigate the potential mucosa impairment in normal-appearing colon mucosa from these patients. MATERIAL AND METHODS Colon polyp patients were prospectively recruited. We obtained colon biopsies from the normal-appearing sites and polyp tissue through colonoscopy. Gene expression analysis was performed using microarrays. Gene ontology and clustering were evaluated by bioinformatics. RESULTS We detected a total of 711 genes (274 up-regulated and 437 down regulated) in polyp tissue and 256 genes (170 up-regulated and 86 down-regulated) in normal-appearing colon mucosa, with at least a 3-fold of change compared to healthy controls. Heatmapping of the gene expression showed similar gene alteration patterns between unaffected colon mucosa and polyp tissue. Gene ontology analyses confirmed the overlapped molecular functions and pathways of altered gene expression between unaffected colon mucosa and polyp tissue from patients with unifocal colon polyp. The most significantly altered genes in normal-appearing tissues in polyp patients include immune response, external side of plasma membrane, nucleus, and cellular response to zinc ion. CONCLUSIONS Significant gene expression alterations exist in unaffected colon mucosa from patients with unifocal colon polyp. Unaffected colon mucosa and polyp tissue share great similarity and overlapping of altered gene expression profiles, indicating the potential possibility of recurrence of colon polyps due to underlying molecular abnormalities of colon mucosa in these patients. PMID- 26675398 TI - Intrapartum sonography - eccentricity or necessity? AB - Ultrasonography has been extensively used in obstetrics and gynecology since 1980's. It found application in pediatric gynecology, procreation period, post menopause, pregnancy monitoring and after delivery. Although the first reports on the use of ultrasonography in assessing delivery mechanism were published in 1990's, yet to date labor progress is evaluated by means of physical examination in most delivery units. Intrapartum sonography is not routinely performed despite the fact that numerous studies documented high error rates of conventional obstetrical examination. Even an experienced physician makes a mistake in every third case of the fetal head descent and fontanelle position assessment. Nowadays, obstetrician's role is not to strain for vaginal delivery at all costs, but to provide the patient in labor and her newborn with maximal safety. To achieve this objective, an obstetrician should distinguish between women who will deliver spontaneously and whose who require Cesarean section. Proper decision should be made on the basis of objective and valid evaluation of obstetric setting, which cannot be achieved solely with physical examination. Intrapartum sonography was shown to be far more accurate than digital examination. Moreover, it is not technically demanding, provides high reproducibility and neither increases the rate of ascending infection or causes discomfort to the patient. Current research suggests that if used routinely, intrapartum sonography can increase the safety of labor and reduce cesarean section rate. PMID- 26675399 TI - Comparison of Perturbed Pathways in Two Different Cell Models for Parkinson's Disease with Structural Equation Model. AB - Increasing evidence indicates that different morphological types of cell death coexist in the brain of patients with Parkinson's disease (PD), but the molecular explanation for this is still under investigation. In this study, we identified perturbed pathways in two different cell models for PD through the following procedures: (1) enrichment pathway analysis with differentially expressed genes and the Reactome pathway database, and (2) construction of the shortest path model for the enriched pathway and detection of significant shortest path model with fitting time-course microarray data of each PD cell model to structural equation model. Two PD cell models constructed by the same neurotoxin showed different perturbed pathways. That is, one showed perturbation of three Reactome pathways, including cellular senescence, chromatin modifying enzymes, and chromatin organization, while six modules within metabolism pathway represented perturbation in the other. This suggests that the activation of common upstream cell death pathways in PD may result in various down-stream processes, which might be associated with different morphological types of cell death. In addition, our results might provide molecular clues for coexistence of different morphological types of cell death in PD patients. PMID- 26675400 TI - Role of epithelial-mesenchymal transition in proliferative vitreoretinopathy. AB - Proliferative vitreoretinopathy (PVR) is a potentially blinding fibrotic complication. It is caused by the formation and contraction of epiretinal membranes (ERMs) that ultimately lead to retinal folds and traction retinal detachments. While multiple cell types have been identified in ERMs, retinal pigment epithelial (RPE) cells have long been implicated as a key player in the pathophysiology of PVR. Clinical and experimental evidence has shown that RPE cells undergo epithelial-mesenchymal transition (EMT) to adopt a fibroblastic phenotype. Cell-cell adhesions maintained by adherens and tight junctions are important for the maintenance of RPE phenotype, and disruption of these junctional complexes results in EMT via activation of signaling pathways such as beta-catenin/Wnt and Hippo signaling, as well as transcription factors involving Zeb1, Snail, and ZONAB. Upon EMT, RPE cells can further differentiate into myofibroblasts in the presence of TGF-beta with cytoskeletal tension mediated by RhoGTPase. These fibroblasts and myofibroblasts derived from RPE cells can contribute to ERM formation by cell migration, proliferation and matrix modification, and play a key role in ERM contraction. It is not solely the proliferation of these cells that results in PVR but rather the contraction of these cells in the ERM. PMID- 26675401 TI - Fibroblast biology in pterygia. AB - Activation of fibroblasts is a vital process during wound healing. However, if prolonged and exaggerated, profibrotic pathways lead to tissue fibrosis or scarring and further organ malfunction. Although the pathogenesis of pterygium is known to be multi-factorial, additional studies are needed to better understand the pathways initiated by fibroblast activation for the purpose of therapeutic translation. Regarding pterygium as a possible systemic disorder, we discuss the different cell types that pterygium fibroblasts originate from. These may include bone marrow-derived progenitor cells, cells undergoing epithelial-mesenchymal transition (EMT), and local resident stromal cells. We also describe how pterygium fibroblasts can be activated and perpetuate profibrotic signaling elicited by various proliferative drivers, immune-inflammation, and novel factors such as stromal cell-derived factor-1 (SDF-1) as well as a known key fibrotic factor, transforming growth factor-beta (TGF-beta). Finally, epigenetic modification is discussed to explain inherited susceptibility to pterygium. PMID- 26675402 TI - Modulation of Smad signaling by non-TGFbeta components in myofibroblast generation during wound healing in corneal stroma. AB - Corneal scarring/fibrosis disturbs normal transparency and curvature of the tissue and thus impairs vision. The lesion is characterized by appearance of myofibroblasts, the key player of the fibrogenic reaction, and excess accumulation of extracellular matrix. Inflammatory/fibrogenic growth factors or cytokines expressed in inflammatory cells that infiltrate into injured tissues play a pivotal role in fibrotic tissue formation. In this article the pathogenesis of fibrosis/scarring in the corneal stroma is reviewed focusing on the roles of myofibroblast, the key player in corneal stromal wound healing and fibrosis, and cytoplasmic signals activated by the fibrogenic cytokine, transforming growth factor beta (TGFbeta). Although it is established that TGFbeta/Smad signal is essential to the process of keratocyte-myofibroblast transformation in a healing corneal stroma post-injury. This article emphasizes the involvement of non-TGFbeta molecular mechanisms in modulating Smad signal. We focus on the roles of matricellular proteins, i.e., osteopontin and tenascin C, and as cellular components, the roles of transient receptor potential (TRP) cation channel receptors are discussed. Our intent is to draw attention to the possibility of signal transduction cascade modulation (e.g., Smad signal and mitogen-activated protein kinases, by gene transfer and other related technology) as being beneficial in a clinical setting to reduce or even prevent corneal stromal tissue fibrosis/scarring and inflammation. PMID- 26675404 TI - Conjunctival fibrosis following filtering glaucoma surgery. AB - Despite advances in surgical technique and postoperative care, fibrosis remains the major impediment to a marked reduction of intraocular pressure without the need of additional medication (complete success) following filtering glaucoma surgery. Several aspects specific to filtering surgery may contribute to enhanced fibrosis. Changes in conjunctival tissue structure and composition due to preceding treatments as well as alterations in interstitial fluid flow and content due to aqueous humor efflux may act as important drivers of fibrosis. In light of these pathophysiological considerations, current and possible future strategies to control fibrosis following filtering glaucoma surgery are discussed. PMID- 26675403 TI - Retinal fibrosis in diabetic retinopathy. AB - In response to injury, reparative processes are triggered to restore the damaged tissue; however, such processes are not always successful in rebuilding the original state. The formation of fibrous connective tissue is known as fibrosis, a hallmark of the reparative process. For fibrosis to be successful, delicately balanced cellular events involving cell proliferation, cell migration, and extracellular matrix (ECM) remodeling must occur in a highly orchestrated manner. While successful repair may result in a fibrous scar, this often restores structural stability and functionality to the injured tissue. However, depending on the functionality of the injured tissue, a fibrotic scar can have a devastating effect. For example, in the retina, fibrotic scarring may compromise vision and ultimately lead to blindness. In this review, we discuss some of the retinal fibrotic complications and highlight mechanisms underlying the development of retinal fibrosis in diabetic retinopathy. PMID- 26675405 TI - Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves' ophthalmopathy. AB - Graves' ophthalmopathy (GO) is an extra-thyroidal complication of Graves' disease (GD; Graves' hyperthyroidism) characterized by orbital tissue inflammation, expansion, remodeling and fibrosis. Although the initiating trigger of GO is still indistinct, excessive orbital fibroblast activity is at the heart of its pathogenesis. Orbital fibroblasts are activated by cellular interactions with immune cells and the soluble factors they secrete. Orbital fibroblasts, especially from GO patients, express the thyrotropin receptor (TSH-receptor; TSHR), and activation of the orbital fibroblast population by stimulatory autoantibodies directed against the TSHR may provide an important link between GD and GO. Furthermore, stimulatory autoantibodies directed against the insulin-like growth factor-1 receptor have been proposed to contribute to orbital fibroblast activation in GO. Activated orbital fibroblasts produce inflammatory mediators thereby contributing to the orbital inflammatory process in GO. Moreover, orbital fibroblasts exhibit robust proliferative activity and extracellular matrix (especially hyaluronan) synthesizing capacity and can differentiate into adipocytes and myofibroblasts with disease progression, thereby contributing to tissue expansion/remodeling and fibrosis in GO. Orbital fibroblasts, especially those from GO patients, exhibit a hyper-responsive phenotype when compared to fibroblasts from other anatomical regions, which may further contribute to GO pathogenesis. Fibrocytes have been identified as additional source of orbital fibroblasts in GO, where they may contribute to orbital tissue inflammation, adipogenesis and remodeling/fibrosis. This review addresses our current view on the role that orbital fibroblasts fulfill in GO pathogenesis and both established as well as less established not fully crystallized concepts that need future studies will be discussed. PMID- 26675406 TI - The role of lamina cribrosa cells in optic nerve head fibrosis in glaucoma. AB - Glaucoma is a chronic progressive optic neuropathy. There are extracellular matrix (ECM) changes associated with optic disc cupping in the optic nerve head (ONH) and subsequent visual field defects. The primary risk factor for onset and progression of glaucoma is raised intraocular pressure (IOP). Elevated IOP causes deformation at the ONH specifically at the lamina cribrosa (LC) region where there is also deposition of ECM causing the LC to initially undergo thickening and posterior migration with eventual shearing and collapse of the LC plates leading to a thin fibrotic connective tissue structure/scar. Cells that populate the LC region of the ONH are those cells that are positive for GFAP (the astrocytes) and those negative for GFAP (the LC cells). The LC cell plays an integral role in ECM remodelling producing ECM when exposed to high level mechanical stretch, TGF- beta1 and a hypoxic environment. PMID- 26675408 TI - The epistemic innocence of psychedelic states. AB - One recent development in epistemology, the philosophical study of knowledge, is the notion of 'epistemic innocence' introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet 'hallucinogen' exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself. PMID- 26675409 TI - A Spectrum of Urological Emergency Reported at a Tertiary Care Teaching Hospital: An Experience. AB - INTRODUCTION: A substantial number of urology admissions constitute of emergency cases and sizeable proportion are urology emergency referral cases. There have been few studies conducted on this aspect but there lie geographical variations in the presentations of urological emergencies. Hence, this study was conducted to analyse various urological emergency presentations and their interventions. OBJECTIVE: To estimate the proportion of urological emergencies and analyse the different type of urological emergencies with the required management. MATERIALS AND METHODS: A hospital based observational descriptive study was undertaken in our institution over a period of one year. RESULTS: A total of 11,139 cases were admitted in the urology department; of which a significant percentage (21.05%) was from emergency room. Majority of cross references came from the Department of Medicine (22.59 %). Renal colic (24.2%) happened to be the most common presentation in emergency room followed by acute urinary retention (14.7%). Among referred cases, hematuria was the leading presentation with 17.75% followed by traumatic catheterization (11.97%). Most common urological intervention in referred cases was supra pubic catheterization (27.20%) while it was percutaneous nephrostomy (32.78%) in directly admitted cases. CONCLUSION: Urological emergencies constitute a significant proportion of total urology admissions (27.18%). The most common non-traumatic injury was renal colic whereas traumatic was traumatic catheterization in our study. Most common surgical intervention in direct admitted emergency cases was percutaneous nephrostomy whereassuprapubic catheterization in within hospital emergency referral cases. PMID- 26675407 TI - The corneal fibrosis response to epithelial-stromal injury. AB - The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ alpha-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or "haze". Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes in corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts produce critical EBM components, such as nidogen-1, nidogen-2 and perlecan, that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self-polymerizes into a nascent EBM. Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte/corneal fibroblast contributions to the nascent EBM. These myofibroblasts, and the opacity they produce, often persist for months or years after the injury. Transparency is subsequently restored when the EBM is completely regenerated, myofibroblasts are deprived of TGFbeta and undergo apoptosis, and the keratocytes re-occupy the anterior stroma and reabsorb disordered extracellular matrix. The aim of this review is to highlight factors involved in the generation of stromal haze and its subsequent removal. PMID- 26675410 TI - The N-terminal domain of the thermo-regulated surface protein PrpA of Enterococcus faecium binds to fibrinogen, fibronectin and platelets. AB - Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 degrees C and 45 degrees C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 degrees C and 37 degrees C. One of the genes that exhibited differential expression between 25 degrees C and 37 degrees C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 degrees C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets. PMID- 26675412 TI - Employment Standards for Australian Urban Firefighters: Erratum. PMID- 26675411 TI - Occupational Medicine Forum: What Online Toxicology Resources Are Available at No Cost From the (US) National Library of Medicine to Assist Practicing OEM Physicians?: Erratum. PMID- 26675413 TI - NYPD Cancer Incidence Rates 1995-2014 Encompassing the Entire World Trade Center Cohort: Erratum. PMID- 26675414 TI - Factors Associated With Truck Crashes in a Large Cross Section of Commercial Motor Vehicle Drivers: Erratum. PMID- 26675415 TI - Comparative Analysis of Disc Diffusion and E-test with Broth Micro-dilution for Susceptibility Testing of Clinical Candida Isolates Against Amphotericin B, Fluconazole, Voriconazole and Caspofungin. AB - BACKGROUND: Antifungal susceptibility testing remains an area of intense interest because of the increasing number of clinical isolates resistant to antifungal therapy. Clinical and Laboratory Standards Institute has proposed reference broth micro dilution (BMD) method for susceptibility testing. The reference method is time-consuming and poorly suited for the routine clinical laboratory setting. Agar-based susceptibility testing methods, disk diffusion (DD) method and the E test method can be an easier, reliable and less time consuming alternative for the BMD method. AIM: To compare the results of Amphotericin B, fluconazole, voriconazole, and Caspofungin susceptibility testing by DD, and the E-test method with the CLSI reference method for clinical Candida isolates. MATERIALS AND METHODS: Broth Microdilution (BMD), E-test and Disk diffusion testing of the various clinical Candida isolates was performed in accordance with CLSI documents. The results obtained were analysed and compared. RESULTS: The categorical agreement for Amphotericin B, fluconazole, voriconazole, and Caspofungin susceptibility results by E-test and DD method was 65.2%, 67.4%; 100%, 82.6%; 100%, 100%; 100%, 97.8% respectively. CONCLUSION: The agar-based E test and disk diffusion methods are reliable alternatives to the BMD method for Candida isolates when test susceptible to fluconazole, voriconazole, and Caspofungin, however the susceptibility testing results must be interpreted with caution in case of Amphotericin B. PMID- 26675416 TI - Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with (44)Sc from cyclotron and from a (44)Ti/(44)Sc generator. AB - The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3AP(PrA) and DO3AP(ABn)) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with (45)Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with (44)Sc was performed using the radioisotope from two sources, a (44)Ti/(44)Sc generator and (44m)Sc/(44)Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 degrees C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of (44)Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the (44)Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine. PMID- 26675417 TI - In Vitro Biosynthesis of the Core Scaffold of the Thiopeptide Thiomuracin. AB - Thiopeptides are potent antibiotics that inhibit protein synthesis. They are made by a remarkable post-translational modification process that transforms a linear peptide into a polycyclic structure. We present here the in vitro biosynthesis of the core scaffold of thiomuracin catalyzed by six proteins. We show that cyclodehydration precedes dehydration, and that dehydration is catalyzed by two proteins in a tRNA(Glu)-dependent manner. The enzyme that generates the pyridine core from two dehydroalanines ejects the leader peptide as a C-terminal carboxamide. Mutagenesis studies of the enzyme TbtD identified important residues for a formal [4+2] cycloaddition process. The core structure of thiomuracin exhibits similar antimicrobial activity to other known congeners, illustrating that in vitro biosynthesis is a viable route to potent antibiotics that can be explored for the rapid and renewable generation of analogues. PMID- 26675418 TI - The effectiveness of communication-skills training interventions in end-of-life noncancer care in acute hospital-based services: A systematic review. AB - OBJECTIVE: A systematic review was conducted in order to explore the effectiveness of communication-skills training interventions in end-of-life care with noncancer acute-based healthcare staff. METHOD: Articles were included if they (1) focused on communication-skills training in end-of-life/palliative care for noncancer acute-based staff and (2) reported an outcome related to behavior change with regard to communication. Sixteen online databases were searched, which resulted in 4,038 potential articles. Screening of titles left 393 articles that met the inclusion criteria. Abstracts (n = 346) and full-text articles (n = 47) were reviewed, leaving 10 papers that met the criteria for our review. All articles explored the effect of communication-skills training on aspects of staff behavior; one study measured the effect on self-efficacy, another explored the impact on knowledge and competence, and another measured comfort levels in discussing the end of life with patients/families. Seven studies measured a number of outcomes, including confidence, attitude, preparedness, stress, and communication skills. RESULTS: Few studies have focused on end-of-life communication-skills training in noncancer acute-based services. Those that do have report positive effects on staff behavior with regard to communication about the end of life with patients and families. The studies varied in terms of the population studied and the health services involved, and they scored only moderately or weakly on quality. It is a challenge to draw a definite conclusion about the effectiveness of training interventions in end-of-life communication because of this. However, the findings from our review demonstrate the potential effectiveness of a range of training interventions with healthcare professionals on confidence, attitude, self-efficacy, and communication skills. SIGNIFICANCE OF RESULTS: Further research is needed to fully explore the effectiveness of existing training interventions in this population, and evidence using objective measures is particularly needed. Ideally, randomized controlled trials or studies using control groups and longer follow-ups are needed to test the effectiveness of interventions. PMID- 26675419 TI - Correlation between expressions of Cyclin-D1, EGFR and p53 with chemoradiation response in patients of locally advanced oral squamous cell carcinoma. AB - INTRODUCTION: Cyclin-D1, p53 and EGFR are molecular markers that regulate the cell cycle and play an important role in tumor progression and development. The present study evaluates the prognostic significance of these markers with chemoradiation response in patients of locally advanced oral squamous cell carcinoma (OSCC). MATERIAL AND METHOD: A total of 97 OSCC patients (females = 19 and males = 78), aged 20-67 years and stage III/IV were recruited. Treatment response was assessed according to WHO criteria. Cyclin-D1, p53 and EGFR expressions in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. RESULTS: The positive expression rates of molecular markers were 86.6% for Cyclin-D1, 92.8% for EGFR and 85.6% for p53. The strong positive expressions of both Cyclin-D1 and p53 showed significant association with poor response. The Cox multivariate regression analysis showed coexpressions of Cyclin-D1 and p53 a significant and independent predictor of overall survival (OR = 1.90, 95% CI = 1.45-4.82, p = 0.046) after adjusting the demographic, clinicopathological and radiological response. The strong positive expressions of Cyclin-D1 and p53 and coexpressions of Cyclin-D1, EGFR and p53 showed significant (p < 0.05 or p < 0.01 or p < 0.001) and lower survival as compared to negative or moderate positive expressions and coexpressions, respectively. CONCLUSION: Expressions and coexpressions of Cyclin-D1 and p53 may serve as a prognostic marker in OSCC patients. PMID- 26675420 TI - Usability evaluation with mental health professionals and young people to develop an Internet-based cognitive-behaviour therapy program for adolescents with anxiety disorders. AB - BACKGROUND: Use of the Internet to deliver cognitive behavioural therapy, a frontline treatment for anxiety disorders, is emerging as an option to increase access to treatment among adolescents with anxiety disorders. This study examined the usability of the Internet-based component of Breathe, a CBT program designed for adolescents with mild to moderate anxiety and impairments. METHODS: A mixed method usability testing design with semi-structured interviews, task completion, and survey by trained usability moderators was undertaken with two interactive cycles to determine the usability (ease of use, efficiency, errors, and user satisfaction) of the user interface and content areas of the program. Purposeful sampling was used to recruit mental health clinicians with expertise in treating adolescent anxiety disorders and young people aged 15 to 24 years involved. Testing involved using Web-conferencing software that allowed remote participation through personal computers. Two testing cycles involved participants completing structured 'think aloud' and 'cognitive walkthrough' tasks within the program. At the end of each cycle participants completed a 15 item global usability evaluation survey and were asked a series of open-ended questions. Descriptive and simple content analyses were used to identify and score usability issues for frequency and severity. RESULTS: Five clinicians and four young people (all < 20 years of age) participated. Most participants described their computer skills as 'good' (60% clinicians, 50% young people), and attitudes toward Internet-based health care ranged from negative (75% young people) to positive (60% clinicians, 25% young people). Scores from the global usability evaluation after both testing cycles ranged from 3.5 to 5 out of 5 in strong agreement/support of the program in terms of user performance indicators (i.e., learnability, efficiency and number of errors) and user satisfaction. Participants were able to complete all critical tasks with minimal errors. Errors and issues identified during testing were predominantly around enhancements to the visual design and navigational support. Opinions across usability elements did not differ between young people and clinician participants. CONCLUSIONS: A multi-method remote usability approach provided the opportunity to improve the technical interface, therapeutic messaging and user experience of an Internet based treatment program for adolescent anxiety disorders. PMID- 26675421 TI - Patterns of cardiovascular disease in a group of HIV-infected adults in Yaounde, Cameroon. AB - BACKGROUND: Cardiovascular disease is an increasingly important issue in human immunodeficiency viral (HIV)-infected individuals. There is dearth of information on the patterns of cardiovascular disease especially in sub-Saharan Africa (SSA) patients. This study reports on the clinical, biological, electrocardiographic and echocardiographic characteristics of a group of HIV-infected patients presenting with symptoms of heart disease in Yaounde, Cameroon. METHODS: This was a cross-sectional study conducted at the Yaounde Central Hospital and Jamot Hospital. Consenting HIV-infected adults aged >=18 years with symptoms suggestive of heart disease were consecutively recruited between February and July 2014. All participants underwent a complete clinical examination; biological analyses including CD4 cell counts, fasting blood glucose, and serum lipids, resting electrocardiography and cardiac ultrasound, and a venous ultrasound where necessary. RESULTS: Forty four subjects (21 men) were included. Their mean age was 48 (SD 13) years. Thirty patients (68.2%) were in WHO clinical stages 3 and 4 of HIV infection, 27 (61.4%) had a CD4 cell count <200/mm(3), and 31 (70.5%) were on antiretroviral therapy (ART). Hypertension (43.2%, n=19) was the most frequent cardiovascular risk factor; and dyslipidemia which was found in 17 subjects (38.6%) was significantly associated with ART (48.4% vs. 15.4%, P=0.04). Only men where smokers (23% vs. 0%, P=0.019). Exertional dyspnea (86.4%, n=38) and cough (59.1%, n=26) were the most frequent symptoms, and the clinical presentation was dominated by heart failure (75%, n=33). The most frequent echocardiographic abnormalities were pericardial effusion (45.5%, n=20) and dilated cardiomyopathy (22.7%, n=10). Dilated cardiomyopathy was significantly associated with CD4 cell counts <200/mm(3) (100%, P=0.003). Primary pulmonary hypertension (PH) rate was 11.4% (n=5) and all cases occurred at CD4 cell counts >=200/mm(3) (P=0.005). The most frequent electrocardiographic abnormalities were abnormal repolarization (59%, n=26) and sinus tachycardia (56.8%, n=25). CONCLUSIONS: Cardiovascular risk factors such as hypertension and dyslipidemia are common in HIV-infected adults with heart disease in our milieu. Advanced HIV infection in adults is associated with a high rate of symptomatic heart disease, mostly effusive pericarditis and dilated cardiomyopathy. Primary PH occurred in less advanced HIV disease. PMID- 26675422 TI - Co-Occurring Atomic Contacts for the Characterization of Protein Binding Hot Spots. AB - A binding hot spot is a small area at a protein-protein interface that can make significant contribution to binding free energy. This work investigates the substantial contribution made by some special co-occurring atomic contacts at a binding hot spot. A co-occurring atomic contact is a pair of atomic contacts that are close to each other with no more than three covalent-bond steps. We found that two kinds of co-occurring atomic contacts can play an important part in the accurate prediction of binding hot spot residues. One is the co-occurrence of two nearby hydrogen bonds. For example, mutations of any residue in a hydrogen bond network consisting of multiple co-occurring hydrogen bonds could disrupt the interaction considerably. The other kind of co-occurring atomic contact is the co occurrence of a hydrophobic carbon contact and a contact between a hydrophobic carbon atom and a pi ring. In fact, this co-occurrence signifies the collective effect of hydrophobic contacts. We also found that the B-factor measurements of several specific groups of amino acids are useful for the prediction of hot spots. Taking the B-factor, individual atomic contacts and the co-occurring contacts as features, we developed a new prediction method and thoroughly assessed its performance via cross-validation and independent dataset test. The results show that our method achieves higher prediction performance than well known methods such as Robetta, FoldX and Hotpoint. We conclude that these contact descriptors, in particular the novel co-occurring atomic contacts, can be used to facilitate accurate and interpretable characterization of protein binding hot spots. PMID- 26675423 TI - Prevalence of bla TEM-220 gene in Penicillinase-producing Neisseria gonorrhoeae strains carrying Toronto/Rio plasmid in Argentina, 2002 - 2011. AB - BACKGROUND: Penicillinase-producing Neisseria gonorroheae (PPNG) was first isolated in 1976. PPNG strains carrying bla TEM-1 and bla TEM-135 gene have been described in different countries. Recently, a novel bla TEM-220 allele was detected in PPNG isolates carrying Toronto/Rio plasmid. The prevalence and characteristics of TEM-220 strains worldwide are unknown, and therefore, it needs to be studied. The purpose of this study was to detect bla TEM-220 gene in PPNG strains possessing Toronto/Rio plasmid over a period of ten years in Argentina, and to evaluate the proportion of isolates producing non-TEM-220 containing the T539C substitution in the bla TEM allele. METHODS: One hundred and fifty one PPNG isolates carrying Toronto/Rio plasmid were studied between 2002 and 2011. A mismatch amplification mutation assay (MAMA) PCR was used to identify the T539C substitution in the bla TEM allele and a MAMA-PCR protocol was developed to detect the G547A substitution in the bla TEM-220. The reference agar dilution method of the Clinical and Laboratory Standard Institute (CLSI) was used for susceptibility testing to five beta-lactams antibiotics, ciprofloxacin, tetracycline and azithromycin. In all TEM-220-producing isolates, the whole bla TEM gene was sequenced and the isolates were typed using N. gonorroheae multiantigen sequence typing (NG-MAST). RESULTS: MAMA PCR successfully identified the G547A substitution in the bla TEM-220 allele. The proportion of isolates that possessed the bla TEM-220 allele was 2.6 %, and 93.2 % MAMA TEM-220 PCR-negative isolates showed the T539C substitution in the bla TEM gene. No differences in the susceptibility to five beta-lactam antibiotics tested were observed in PPNG isolates TEM-220-producing and PPNG isolates carrying the T539C substitution in the bla TEM gene. All TEM-220 isolates were indistinguishable by NG-MAST. CONCLUSION: This is the first study which shows the prevalence of bla TEM-220 in N. gonorrhoeae isolates carrying Toronto/Rio plasmid in Argentina. Although the bla TEM-220 allele does not appear to be associated with an extended spectrum beta-lactamase (ESBL) phenotype of resistance, a single nucleotide polymorphism added to the bla TEM-220 or bla TEM containing the T539C substitution could lead to the emergence of ESBL. Thus, it is imperative to investigate in surveillance programs, not only the plasmid type in PPNG isolates and the bla TEM allele associated, but phenotypical characteristics and geographical distribution of isolates. PMID- 26664704 TI - Case Report: Severe acute respiratory distress by tracheal obstruction due to a congenital thyroid teratoma. AB - Congenital teratoma is a rare condition and is a germ cell tumor composed of elements from one or more of the embryonic germ layers and contain tissues usually foreign to the anatomic site of origin. We report a case of a neck tumor diagnosed during pregnancy, initially thought to be a goiter. After birth the neck mass kept growing until it compressed the trachea and produced respiratory failure. The infant had a difficult tracheal intubation because of the compressing mass. The staff decided to surgically remove the neck mass. After that, the infant became eupneic. The histological analysis showed a mature teratoma with no atypias. PMID- 26675424 TI - Biochemical toxicity and DNA damage of imidazolium-based ionic liquid with different anions in soil on Vicia faba seedlings. AB - In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl), 1-octyl-3-methylimidazolium bromide ([Omim]Br) and 1-octyl-3 methylimidazolium tetrafluoroborate ([Omim]BF4) in soil on Vicia faba (V. faba) seedlings at 0, 100, 200, 400, 600 and 800 mg kg(-1) were assessed for the first time at the cellular and molecular level. Moreover, the toxicity of these three ionic liquids (ILs) was evaluated, and the influence of anions on the toxicity of the ILs was assessed. The results showed that even at 100 mg kg(-1), the growth of V. faba seedlings was inhibited after exposure to the three ILs, and the inhibitory effect was enhanced with increasing concentrations of the three ILs. The level of reactive oxygen species (ROS) was increased after exposure to the three ILs, which resulted in lipid peroxidation, DNA damage and oxidative damage in the cells of the V. faba seedlings. In addition, the anion structure could influence the toxicity of ILs, and toxicity of the three tested ILs decreased in the following order: [Omim]BF4 > [Omim]Br > [Omim]Cl. Moreover, oxidative damage is the primary mechanism by which ILs exert toxic effects on crops, and ILs could reduce the agricultural productivity. PMID- 26675427 TI - Pharmacogenetics: HCRTR2 gene is associated with response to HF therapy. PMID- 26675426 TI - Analysis of Biobanked Serum from a Mycobacterium avium subsp paratuberculosis Bovine Infection Model Confirms the Remarkable Stability of Circulating miRNA Profiles and Defines a Bovine Serum miRNA Repertoire. AB - Johne's Disease (JD) is a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Current disease control strategies are hampered by the lack of sensitive and specific diagnostic modalities. Therefore, novel diagnostic and prognostic tools are needed, and circulating microRNAs (miRNAs) may hold potential in this area. The aims of this study were twofold: (i) to address the stability of miRNA in bovine sera from biobanked samples, and (ii) to assess the potential of miRNAs as biomarkers for JD disease progression. To address these aims we used bovine sera from an experimental MAP infection model that had been stored at -20 degrees C for over a decade, allowing us to also assess the stability of miRNA profiles in biobanked serum samples through comparison with fresh sera. Approximately 100-200 intact miRNAs were identified in each sample with 83 of these being consistently detected across all 57 samples. The miRNA profile of the biobanked sera stored at -20 degrees C for over 10 years was highly similar to the profile of <1 year-old sera stored at -80 degrees C, with an overlap of 73 shared miRNAs. IsomiR analysis also indicated a distinct bovine serum-specific isomiR profile as compared to previously reported bovine macrophage miRNA profiles. To explore the prognostic potential of miRNA profiles cattle defined as seropositive for anti-MAP antibodies (n = 5) were compared against seronegative cattle (n = 7). No significant differential expressed miRNAs were detected at either the early (6 months) or late (43, 46 and 49 months) intervals (FDR<=0.05, fold-change>=1.5) across seropositive or seronegative animals. However, comparing pre-infection sera to the early and late time-points identified increased miR-29a and miR-92b abundance (2-fold) that may be due to blood-cell population changes over time (P<0.001). In conclusion our study has demonstrated that bovine circulating miRNAs retain their integrity under long-term sub-optimal storage temperatures opening the way for increased miRNA analyses from biobanked samples for a range of infectious and non infectious diseases. PMID- 26675437 TI - New Insights into Peptide-Silver Nanoparticle Interaction: Deciphering the Role of Cysteine and Lysine in the Peptide Sequence. AB - We studied the interaction of four new pentapeptides with spherical silver nanoparticles. Our findings indicate that the combination of the thiol in Cys and amines in Lys/Arg residues is critical to providing stable protection for the silver surface. Molecular simulation reveals the atomic scale interactions that underlie the observed stabilizing effect of these peptides, while yielding qualitative agreement with experiment for ranking the affinity of the four pentapeptides for the silver surface. PMID- 26675438 TI - Facile synthesis of para-[(18)F]fluorohippurate via iodonium ylide-mediated radiofluorination for PET renography. AB - para-[(18)F]fluorohippurate ([(18)F]PFH) is a renal tubular agent suitable for conducting positron emission tomography (PET) renography. [(18)F]PFH is currently synthesized by a four-step two-pot procedure utilizing a classical prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate, followed by glycine conjugation. Considering the short half-life of fluorine-18 (110min), it is important to reduce the number of synthetic steps and overall production time for successful translation of any fluorine-18 radiopharmaceutical in to clinical practice. Here, we report a new two-step one-pot procedure using a novel spirocyclic iodonium ylide precursor for producing a dose of [(18)F]PFH suitable for human use in 45min including HPLC purification with an overall decay-corrected radiochemical yield of 46.4+/-2.9% (n=3) and radiochemical purity of >99%. PMID- 26675439 TI - Polyphenols isolated from leaves of Vitis thunbergii var. taiwaniana regulate APP related pathway. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major component of the plaques, amyloid-beta (Abeta), is generated from amyloid beta precursor protein (APP) by beta- and gamma-secretase-mediated cleavages. Multiple lines of evidence demonstrate that overproduction/accumulation of Abeta in vulnerable brain regions is a primary cause of the pathogenesis of AD. Among the twelve polyphenols isolated from the leaf extracts of Vitis thunbergii var. taiwaniana (VTT), stenophyllol C, stenophyllol B, ampelopsin C, vitisin A, and davidiol A were shown to significantly reduce both Abeta40 and Abeta42 levels in N2a695 cells. Further studies revealed that ampelopsin C and vitisin A reduce Abeta production through inhibiting beta-secretase activity, while the effects of the other active polyphenols on reducing Abeta generation are through different mechanisms. These results suggest that VTT extracts may be beneficial for AD prevention and treatment. PMID- 26675440 TI - Identification of a novel class of quinoline-oxadiazole hybrids as anti tuberculosis agents. AB - A series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. The hybrid compounds synthesized were screened for biological activity against Mycobacterium tuberculosis H37Rv and for cytotoxicity in HepG2 cell line. Several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed minimum inhibitory concentration values<0.5MUM and selectivity index>500. The results of this study open up a promising avenue that may lead to the discovery of a new class of anti tuberculosis agents. PMID- 26675442 TI - Erratum. AB - [This corrects the article DOI: 10.1159/000439080.]. PMID- 26675443 TI - G protein-coupled receptors: potential therapeutic targets for diabetic nephropathy. AB - Diabetic nephropathy, a lethal microvascular complication of diabetes mellitus, is characterized by progressive albuminuria, excessive deposition of extracellular matrix, thickened glomerular basement membrane, podocyte abnormalities, and podocyte loss. The G protein-coupled receptors (GPCRs) have attracted considerable attention in diabetic nephropathy, but the specific effects have not been elucidated yet. Likewise, abnormal signaling pathways are closely interrelated to the pathologic process of diabetic nephropathy, despite the fact that the mechanisms have not been explored clearly. Therefore, GPCRs and its mediated signaling pathways are essential for priority research, so that preventative strategies and potential targets might be developed for diabetic nephropathy. This article will give us comprehensive overview of predominant GPCR types, roles, and correlative signaling pathways in diabetic nephropathy. PMID- 26675441 TI - Discovery of highly potent and selective Bruton's tyrosine kinase inhibitors: Pyridazinone analogs with improved metabolic stability. AB - BTK inhibitor GDC-0834 (1) was found to be rapidly metabolized in human studies, resulting in a suspension of clinical trials. The primary route of metabolism was through cleavage of the acyclic amide bond connecting the terminal tetrahydrobenzothiophene with the central linker aryl ring. SAR studies were focused on reducing metabolic cleavage of this amide, and resulted in the identification of several central aryl linker substituents that conferred improved stability. The most promising substituted aryl linkers were then incorporated into an optimized pyridazinone scaffold, resulting in the identification of lead analog 23, possessing improved potency, metabolic stability and preclinical properties. PMID- 26675444 TI - Implementing an opioid risk assessment telephone clinic: Outcomes from a pharmacist-led initiative in a large Veterans Health Administration primary care clinic, December 15, 2014-March 31, 2015. AB - BACKGROUND: In response to the national epidemic of prescription opioid misuse and related adverse outcomes, two clinical pharmacists developed a telephone risk assessment clinic to promote safe opioid prescribing through a monthly assessment of patient medication use, aberrant behaviors, and side effects. METHODS: A pilot group of five primary care providers and their patients with chronic nonmalignant pain on chronic opioid therapy, defined as having received prescription opioid medications for >=90 days in the last 120 days, were identified. A risk assessment evaluation based on Veterans Health Administration/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain was created. Factors assessed were receipt of non-San Francisco Veterans Administration Health Care System controlled substance prescriptions through California's prescription drug monitoring program, urine drug test (UDT) results, and aberrant behaviors. Pharmacist-recommended changes to regimen and provider response to recommendation were compiled. The pilot was conducted from December 15, 2014, to March 31, 2015. RESULTS: Among 608 patients on chronic opioid therapy, 148 were assigned to pilot providers and 447 assessments were completed. Twenty-five (16.8%) patients had non-VA controlled substance prescriptions, of which 14 (56.0%) patients filled a non-VA controlled substance within 3 months of the start of pilot. Seventeen UDT results inconsistent with their prescribed regimens were identified from 12 patients (8.1%). Pharmacists recommended 66 changes to chronic opioid prescriptions in 48 patients (32.4%), including decreasing quantity of opioid(s) (33.3%), discontinuing chronic opioid therapy (22.7%), and delaying a fill (19.7%). Sixty-one of 66 (92.5%) pharmacist recommendations for regimen change were implemented by providers. Chronic opioid therapy was discontinued in 14 (9.5%) patients over the course of the pilot study. CONCLUSIONS: A pharmacist-led telephone risk assessment clinic improved adherence to clinical guidelines and changed opioid prescribing practices in more than one third of assessed patients. PMID- 26675445 TI - Comparison of Root Surface Roughness Produced By Hand Instruments and Ultrasonic Scalers: An Invitro Study. AB - BACKGROUND: Instrumentation on tooth surface for debridement of hard and soft debris forms the basis of periodontal therapy. This involves periodic removal of accumulated material using different methods of instrumentation. An ideal instrument should eliminate all the deposits from the root surfaces with no or minimal alteration of the natural morphology. AIM: To compare the root surface roughness after root planing performed with gracey curette and by ultrasonic scalers (Satelec P-5 Booster) set at different power modes. MATERIALS AND METHODS: The root surface roughness and its surface microtopography resulting from the use of Gracey curette, ultrasonic instrument at low, medium and high power setting on 35 healthy premolars extracted for orthodontic treatment purpose were examined using Optical Profilometer and the surface topography was assessed using Field Emission Microscope. STATISTICAL ANALYSIS: Analysis of variance (ANOVA) test was used to observe the variance in a particular variable is partitioned into components attributable to different sources of variation. Duncan multiple range tests were used to determine whether three or more means differ significantly. RESULTS AND CONCLUSION: The mean roughness was found to be the highest in group where Scaling and Root Planing (SRP) was performed using ultrasonic scaler at low power mode (3.03+/-1.54 MUm) whereas the lowest surface roughness was seen on the samples where SRP was performed using ultrasonic scaler at medium power mode. The surface roughness in group where SRP was performed with ultrasonic scaler at high power mode (2.22+/-0.74MUm) was found to be similar to that of group in which root planing was carried out using curette (2.24+/ 1.71MUm). PMID- 26675446 TI - Out-of-hospital cardiac arrest in adults: lowering body temperature. AB - INTRODUCTION: Post-resuscitation care after return of spontaneous circulation is critical to improving patient outcomes in sudden cardiac death. Therapeutic hypothermia has been a mainstay of treatment after successful cardiopulmonary resuscitation in the setting of ventricular fibrillation or pulseless ventricular tachycardia. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of lowering body temperature for comatose survivors of out-of-hospital cardiac arrest associated with ventricular tachycardia or ventricular fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 222 studies. After deduplication and removal of conference abstracts, 114 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 89 studies and the further review of 25 full publications. Of the 25 full articles evaluated, one systematic review included in a previous version was updated and three RCTs were added at this update. We performed a GRADE evaluation for five PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for three interventions based on information about the effectiveness and safety of therapeutic hypothermia, different lower body temperatures, and different durations of lower body temperatures. PMID- 26675447 TI - Optical signaling in biofluids: a nondenaturing photostable molecular probe for serum albumins. AB - The systematic investigation of the interaction of a new class of molecular materials with proteins through structure-optical signaling relationship studies has led to the development of efficient fluorescent probes that can detect and quantify serum albumins in biofluids without causing any denaturation. PMID- 26675448 TI - Effect of Ionizing and Non-ionizing Radiation On Amalgam, Composite and Zirconomer Based Restorations. PMID- 26675449 TI - Genetic Structure and Molecular Diversity of Cacao Plants Established as Local Varieties for More than Two Centuries: The Genetic History of Cacao Plantations in Bahia, Brazil. AB - Bahia is the most important cacao-producing state in Brazil, which is currently the sixth-largest country worldwide to produce cacao seeds. In the eighteenth century, the Comum, Para and Maranhao varieties of cacao were introduced into southern Bahia, and their descendants, which are called 'Bahian cacao' or local Bahian varieties, have been cultivated for over 200 years. Comum plants have been used to start plantations in African countries and extended as far as countries in South Asia and Oceania. In Brazil, two sets of clones selected from Bahian varieties and their mutants, the Agronomic Institute of East (SIAL) and Bahian Cacao Institute (SIC) series, represent the diversity of Bahian cacao in germplasm banks. Because the genetic diversity of Bahian varieties, which is essential for breeding programs, remains unknown, the objective of this work was to assess the genetic structure and diversity of local Bahian varieties collected from farms and germplasm banks. To this end, 30 simple sequence repeat (SSR) markers were used to genotype 279 cacao plants from germplasm and local farms. The results facilitated the identification of 219 cacao plants of Bahian origin, and 51 of these were SIAL or SIC clones. Bahian cacao showed low genetic diversity. It could be verified that SIC and SIAL clones do not represent the true diversity of Bahian cacao, with the greatest amount of diversity found in cacao trees on the farms. Thus, a core collection to aid in prioritizing the plants to be sampled for Bahian cacao diversity is suggested. These results provide information that can be used to conserve Bahian cacao plants and applied in breeding programs to obtain more productive Bahian cacao with superior quality and tolerance to major diseases in tropical cacao plantations worldwide. PMID- 26675450 TI - Multiple sclerosis retrovirus-like envelope gene: Role of the chromosome 20 insertion. AB - BACKGROUND: The genetic basis involved in multiple sclerosis (MS) susceptibility was not completely revealed by genome-wide association studies. Part of it could lie in repetitive sequences, as those corresponding to human Endogenous Retroviruses (HERVs). Retrovirus-like particles were isolated from MS patients and the genome of the MS-associated retrovirus (MSRV) was the founder of the HERV W family. We aimed to ascertain which chromosomal origin encodes the pathogenic ENV protein by genomic analysis of the HERV-W insertions. METHODS/RESULTS: In silico analyses allowed to uncover putative open reading frames containing the specific sequence previously reported for MSRV-like envelope (env) detection. Out of the 261 genomic insertions of HERV-W env, only 9 copies harbor the specific primers and probe featuring MSRV-like env. The copy from chromosome 20 was further studied considering its size, a truncated homologue of the functional HERV-W env sequence encoding syncytin. High Resolution Melting analysis of this sequence identified two single nucleotide polymorphisms, subsequently genotyped by Taqman chemistry in 668 MS patients and 678 healthy controls. No significant association of these polymorphisms with MS risk was evidenced. Transcriptional activity of this MSRV-like env copy was detected in peripheral blood mononuclear cells from patients and controls. RNA expression levels of chromosome 20-specific MSRV-like env did not show significant differences between MS patients and controls, neither were related to genotypes of the two mentioned polymorphisms. CONCLUSIONS: The lack of association with MS risk of the identified polymorphisms together with the transcription results discard chromosome 20 as genomic origin of MSRV-like env. PMID- 26675451 TI - Mitochondrial Cytochrome Oxidase I Gene Sequence Analysis of Aedes Albopictus in Malaysia. AB - A study was conducted to establish polymorphic variation of the mitochondrial DNA encoding the cytochrome oxidase subunit 1 (CO1) gene in Aedes albopictus isolated from 2 hot spot dengue-infested areas in the Subang Jaya District, Malaysia. A phylogenetic analysis was performed with the use of sequences obtained from USJ6 and Taman Subang Mas (TSM). Comparison of the local CO1 sequences with a laboratory strain (USM), alongside reference strains derived from the GenBank database revealed low genetic variation in terms of nucleotide differences and haplotype diversity. Four methods were used to construct a phylogenetic tree and illustrate the genetic relationship of the 37 Ae. albopictus populations based on the CO1 sequences, namely neighbor-joining (NJ), maximum parsimony (MP), maximum likelihood (ML), and Bayesian method, which revealed a distinct relationship between isolates from USJ6 and TSM. Our findings provide new information regarding the genetic diversity among morphologically similar Ae. albopictus, which has not been reported to date. PMID- 26675452 TI - Interspecific Cross-Mating Between Aedes aegypti and Aedes albopictus Laboratory Strains: Implication of Population Density on Mating Behaviors. AB - Mating behavior between Aedes aegypti and Ae. albopictus, established colony strains were examined under laboratory conditions (30-cm(3) screened cages) for 5 consecutive days. The effect of selected male densities (30, 20, 10) and female density (20) on the number of swarming, mating pairs, eggs produced, and inseminated females were evaluated. Male densities significantly increased swarming behavior, mating pairs, and egg production of heterospecific females, but female insemination was reduced. Aedes aegypti males mate more readily with heterospecific females than do Ae. albopictus males. The current study suggests that Ae. aegypti males were not species-specific in mating, and if released into the field as practiced in genetically modified mosquito techniques, they may mate with both Ae. aegypti and Ae. albopictus females, hence reducing populations of both species by producing infertile eggs. PMID- 26675453 TI - The Effects of Larval Habitat Quality on Aedes albopictus Skip Oviposition. AB - Aedes albopictus is an invasive mosquito species that transmits human-disease causing pathogens. It is a container-inhabiting species that oviposits in resource-limited habitats. To mitigate larval competition, Ae. albopictus females may choose to distribute eggs from a single gonotrophic cycle among multiple containers through skip oviposition. With the use of individual females released in indoor and outdoor caged trials, we evaluated the oviposition choices made by gravid Ae. albopictus offered larval habitats with different qualities. Our results demonstrate that Ae. albopictus performs skip oviposition and that the degree of egg distribution is related to the quality of the larval habitat. In a 4-choice arena, individual Ae. albopictus oviposited in fewer containers when presented with ovisites of high-quality larval habitat (uncrowded conditions) compared with oviposition in low-quality (crowded conditions) larval habitats. Additionally, the females selectively oviposited in high-quality habitats when offered both low- and high-quality habitats, but distributed eggs more evenly among multiple high-quality habitats. Our results have important implications for mosquito management plans that include the use of lethal ovitraps, as well as the role of this behavior in distribution of disease-causing pathogens. PMID- 26675454 TI - Host-Seeking Behavior and Arbovirus Detection in Mosquitoes of Habahe County, Xinjiang Uigur Autonomous Region, China. AB - Mosquitoes in Habahe County of Xinjiang Uigur Autonomous Region in China are considered a serious nuisance problem to local residents, but little is known of their role in enzootic disease. Therefore, host-seeking behavior and virus detection in mosquitoes were investigated in this study. Adult host-seeking mosquitoes were sampled using the Centers for Disease Control and Prevention (CDC) light traps operated at three locations in June through August 2008. Nine traps were used at each location at 3 different heights (1 m, 3 m, and 5 m). Seven mosquito species from 4 genera were collected by CDC light traps in different habitats. In total, 90,055 mosquitoes were captured, of which Aedes vexans was the most abundant species, comprising 88.02% of all mosquitoes collected. The second most abundant species was Anopheles messese, which comprised about 5.86%. Other species caught were Culex modestus (2.89%), Aedes caspius (1.11%), Coquillettidia richiardii (0.61%), Ae. dorsalis (1.36%), and An. hyrcanus (0.14%). About 93.5% of Ae. vexans individuals were caught in CO2-baited CDC light traps at 1 m above the ground. The highest numbers of Cx. modestus were caught at the highest trap level, 5 m above ground. Overall, significantly more mosquitoes of all species were collected at dusk than at dawn. Based on blood meal analyses, Ae. vexans and An. messese fed on various vertebrate hosts, whereas Cx. modestus fed on ducks only. From a total of 335 mosquito pools tested, 10 pools of Ae. vexans were found positive for alphavirus. Comparison with the gene database revealed that the alphavirus deoxyribonucleic acid fragment obtained (GenBank accession no. HM160530) was 100% homologous at the nucleotide level to chikungunya virus isolate LK (PB) chik3408, chikungunya virus isolate SGEHICHD122508, and chikungunya virus strain FD080231. The results of this study suggest that ongoing, integrated mosquito and arbovirus surveillance is necessary in this river wetland. PMID- 26675455 TI - An Updated Checklist of the Mosquitoes of Oklahoma Including New State Records and West Nile Virus Vectors, 2003-06. AB - The mosquito fauna of Oklahoma has not been evaluated since 1965 and no report has been published concerning species associated with urban areas in the state. Mosquito collections were conducted as part of the West Nile virus (WNV) surveillance program between April and November from 2003 to 2006, using standard collection methods. A total of 74,756 adults were collected in 26 urban centers in 16 counties of Oklahoma. Altogether, 40 species were recorded during this study period, bringing the total mosquito species recorded in Oklahoma to 62 species in 9 different genera and 18 subgenera. An updated checklist of Oklahoma mosquito fauna is included with a comparison to historical records. New state records include 3 species: Aedes muelleri, Anopheles perplexens, and Culex coronator. In addition to updating the checklist, 12 species of mosquitoes were tested for WNV. Pools of Culex pipiens complex represented the highest proportion testing positive for WNV (134/766, 17.5%), followed by Cx. tarsalis (13/192, 6.8%) and Aedes albopictus (5/215, 2.3%). West Nile virus-positive mosquitoes were detected earliest in June 2005 and latest in November 2004. Infected Cx. pipiens complex testing positive for WNV were more prevalent in the eastern and central areas of Oklahoma, whereas positive Cx. tarsalis were found mainly in the western areas of the state. This distinct geographical difference needs to be monitored and followed up to ensure optimal mosquito control efforts in Oklahoma communities with mosquito control capabilities. PMID- 26675456 TI - Establishment of Diagnostic Doses of Five Pyrethroids for Monitoring Physiological Resistance in Aedes Albopictus in Thailand. AB - Monitoring insecticide resistance of Aedes albopictus is required for implementing effective dengue and chikungunya vector control in Thailand. The World Health Organization standard susceptibility test for adult mosquitoes was used to determine the baseline susceptibility of a pyrethroid-susceptible laboratory strain of Ae. albopictus to 5 different pyrethroids (deltamethrin, permethrin, bifenthrin, cypermethrin, and alpha-cypermethrin). Subsequently, the respective established diagnostic doses (0.026% deltamethrin, 1.024% permethrin, 0.570% bifenthrin, 0.237% cypermethrin, and 0.035% alpha-cypermethrin) were used to test field-collected Ae. albopictus from Rayong, Koh Chang, and Pong Nom Ron. As expected, the laboratory strain was completely susceptible to all pyrethroid insecticides at the established concentrations. Rayong mosquitoes were found to be highly susceptible to bifenthrin, cypermethrin, and alpha-cypermethrin. Koh Chang mosquitoes were susceptible to only deltamethrin and permethrin. Pong Nom Ron mosquitoes were resistant to all pyrethroids tested. Routine assessment of these baseline results should guide future resistance monitoring to pyrethroid insecticides in Ae. albopictus in Thailand. PMID- 26675457 TI - Suitability of Mixing Fluorescent Dye in Adulticides and its Impact on Droplet Characteristics and Pesticide Efficacy. AB - Fluorescent dyes are commonly used to help visualize insecticidal droplets or to trace movement of insecticides; however, the effect these dyes have on the insecticide's efficacy and droplet characteristics is unknown. This study evaluated the effects of mixing Uvitex OB fluorescent dye with 5 adulticides on their efficacy in a wind tunnel. Efficacy was determined via droplet size characteristics, spray flux (active ingredient [AI] deposition), and female adult Aedes aegypti mortality. Fyfanon(r) ULV, Anvil(r) 10+10, DuetTM, Aqualuer(r) 20 20, and Zenivex(r) E20, diluted with corn oil, were tested with and without the dye at maximum, minimum, and half-minimum label rates. Adulticide droplet size was not affected by the addition of dye to any of the 5 pesticides tested. Mosquito mortality was strongly correlated with AI deposition for all pesticides except Duet. There was no difference among correlation coefficients of the 5 pesticides and between coefficients of any pesticide pairs, indicating that all correlations were similar. The addition of dye slightly but nonsignificantly and nonconsistently affected mortality. It was found that the source of this variability was due to large variation in mortality among different replicates of the same treatment. PMID- 26675458 TI - A Mosquito Survey of the Twin-Island Caribbean Nation of Saint Kitts and Nevis, 2010. AB - Adult mosquito surveys of Saint Kitts and Nevis (SKN) were performed in the dry season (March 16-23, 2010) in Saint Kitts, and the rainy season (October 18-25, 2010) in SKN. Biogents (BG) Sentinel Traps were set with CO2and BG Lure in urban, rural, mangrove, and dry forest habitats. Mosquitoes were identified to species, and reverse transcription-polymerase chain reaction was performed on potential vector species for dengue virus (DENV), chikungunya virus (CHIKV), and West Nile virus (WNV). The most abundant species during both seasons in St. Kitts were Culex quinquefasciatus, Aedes taeniorhynchus, and Aedes aegypti. There were 3 new records for Saint Kitts: Aedes tortilis, Anopheles albimanus, and Culex nigripalpus. Traps were also set in Nevis. No mosquito pool tested positive for DENV, CHIKV, or WNV. PMID- 26675459 TI - Overwintering of Uranotaenia Unguiculata Adult Females in Central Europe: A Possible Way of Persistence of the Putative New Lineage of West Nile Virus? AB - We report the overwintering of Uranotaenia unguiculata adult females in Central Europe (Czech Republic, Hungary, Austria). This finding suggests a potential mode of winter persistence of putative novel lineage of West Nile virus in the temperate regions of Europe. PMID- 26675460 TI - Efficacy of Two LarvasonicTM Units Against Culex Larvae and Effects on Common Aquatic Nontarget Organisms in Harris County, Texas. AB - The LarvasonicTM Field Arm Mobile Wetlands Unit and SD-Mini were tested for efficacy against Culex larvae, and effects on aquatic nontarget organisms (NTO). The Field Arm provided 84.61% to 100% control of caged Culex larvae out to 0.91-m distance in shallow ditches and 60.45% control of Culex larvae at 0.61-m without any effects to caged NTO. Slow ditch treatment achieved 77.35% control compared to fast treatment (20.42%), whereas 77.65% control was obtained along edges of a neglected swimming pool, compared to near the middle (23.97%). In bucket tests, the SD-Mini provided >97% control of Culex and 85.35% reduction of immature giant water bugs, which decreased slightly (83.45%) over the monitoring period, which was not significantly different from cannibalistic damselflies (62.80%), with reduction of both being significantly higher than other NTO tested. There was a small (0.37%) reduction of dragonflies (naiads), due to cannibalism. Both Larvasonic units could effectively augment conventional larvicide operations in smaller areas without causing resistance within mosquito populations or harming NTO when used properly. PMID- 26675461 TI - Evaluating the Use of Commercial West Nile Virus Antigens as Positive Controls in the Rapid Analyte Measurement Platform West Nile Virus Assay. AB - We evaluated the utility of 2 types of commercially available antigens as positive controls in the Rapid Analyte Measurement Platform (RAMP(r)) West Nile virus (WNV) assay. Purified recombinant WNV envelope antigens and whole killed virus antigens produced positive RAMP results and either type would be useful as a positive control. Killed virus antigens provide operational and economic advantages and we recommend their use over purified recombinant antigens. We also offer practical applications for RAMP positive controls and recommendations for preparing them. PMID- 26675462 TI - Effects of a Red Marker Dye on Aedes and Culex Larvae: Are There Implications for Operational Mosquito Control? AB - Marker dyes are often mixed with liquid insecticide formulations prior to field applications to accurately determine the characteristics and penetration of droplets into targeted habitats. We have been using FD&C Red 40 Granular DM food dye at the rate of 20 g/liter in liquid solutions of Bacillus thuringiensis israelensis (Bti) for area-wide larvicide applications against the Asian tiger mosquito, Aedes albopictus. The Bti and dye mix ratio has been recommended by pesticide manufacturers for testing under operational conditions, but no data exist on the effects of the dye itself on mosquito larvae. We tested the effects of the FD&C Red 40 food dye in laboratory bioassays against different strains of Ae. albopictus (New Jersey and Maryland) and Culex pipiens pipiens (Utah) at rates of 0.039 to 80.0 g/liter. We also conducted field application trials to measure dye concentrations up to 100 m downwind when mixed and applied according to manufacturer instructions. In laboratory bioassays, we found that mean survival in cups with dye were significantly different from the controls beginning at 10.0 g/liter for New Jersey Ae. albopictus and at 20.0 g/liter for Maryland Ae. albopictus and Utah Cx. p. pipiens. In field application trials, we recorded a maximum volume density of 1,152.8 nl/cm(2) and calculated the maximum concentration of dye at 9.09 * 10(-3) g/liter. Our results showed that although we detected greater effects of dye on Ae. albopictus in New Jersey experiments than Ae. albopictus in Maryland and Cx. p. pipiens from Utah, concentrations of the dye during operational applications were at least 1,100 times below concentrations that exhibited toxic effects for either species in the laboratory, suggesting that the dye will not interfere with accuracy of field bioassays. Our results conclusively demonstrate that the addition of the FD&C Red 40 marker dye does not alter the efficacy of the pesticide formulation by skewing results, but rather provides a valuable addition to accurately determine pesticide penetration and spectrum by discriminating between intended pesticide and other potential pollutants. PMID- 26675464 TI - Comparison of Trapping Performance Between the Original BG-Sentinel(r) Trap and BG-Sentinel 2(r) Trap (1). AB - Recently, the BG-Sentinel(r) trap (BGS) trap has been reconfigured for increased durability during harsh field conditions. We evaluated the attractiveness of this redesigned trap, BG-Sentinel 2(r) (BGS2), and its novel granular lure cartridge system relative to the original trap and lure. Granular lures containing different combinations of lactic acid, ammonia, hexanoic acid, and octenol were also evaluated. Lure cartridges with all components except octenol trapped significantly more Aedes albopictus than lures containing octenol. This new granular lure combination and original BG-Lure(r) system were paired with BGS and BGS2 traps to compare relative attractiveness of the lures and the traps. All evaluations were conducted under field conditions in a suburban neighborhood in northeastern Florida from July to October 2014. Overall, the average numbers of Ae. albopictus collected by BGS or BGS2 were similar regardless of the lure type (i.e., mesh bag versus granules) (P = 0.56). The functionality and durability of both trap models are discussed. PMID- 26675463 TI - Laboratory Validation of the Sand Fly Fever Virus Antigen Assay. AB - Sandfly fever group viruses in the genus Phlebovirus (family Bunyaviridae) are widely distributed across the globe and are a cause of disease in military troops and indigenous peoples. We assessed the laboratory sensitivity and specificity of the Sand Fly Fever Virus Antigen Assay, a rapid dipstick assay designed to detect sandfly fever Naples virus (SFNV) and Toscana virus (TOSV) against a panel of phleboviruses. The assay detected SFNV and TOSV, as well as other phleboviruses including Aguacate, Anahanga, Arumowot, Chagres, and Punta Toro viruses. It did not detect sandfly fever Sicilian, Heartland, Rio Grande, or Rift Valley fever viruses. It did not produce false positive results in the presence of uninfected sand flies (Lutzomyia longipalpis) or Cache Valley virus, a distantly related bunyavirus. Results from this laboratory evaluation suggest that this assay may be used as a rapid field-deployable assay to detect sand flies infected with TOSV and SFNV, as well as an assortment of other phleboviruses. PMID- 26675465 TI - Comparison of Indoor Residual Spray Equipment for Malaria Control in Liberia. AB - We describe and compare a new innovative backpack compressed-air sprayer (JQSX 12) to a Stihl(r) 450 backpack mist blower and a manually operated compression sprayer for its effectiveness as an alternative operational tool for indoor residual insecticide application to control malaria in Liberia. Advantages and physical characteristics of each sprayer and their spray atomization parameters are discussed. PMID- 26675466 TI - 2015 AMCA Memorial Lecture Honoree: Dr. Richard Floyd Darsie, Jr. AB - Richard Floyd Darsie, Jr. (1915-2014) is the 2015 American Mosquito Control Association Memorial Lecture Honoree. He was one of the greatest mosquito taxonomists of the 20th century and died peacefully on April 10, 2014, in Grove City, PA, at the age of 99 after a professional career that spanned eight decades. Dick's broad areas of interest and training made him a versatile scientist, teacher, and researcher. His intense interest in adult and immature mosquito morphology and taxonomy, as well as mosquito distribution and bionomics, started early in his career at two early academic postings: Franklin and Marshall College (1949-54) and the University of Delaware (1954-62). Dick would take his mosquito interests with him to postings and research projects around the world: Nepal, the Philippines, Atlanta, El Salvador, Guatemala, Fort Collins, South Carolina, Argentina, and Florida. His travels and studies would make him an international expert on mosquito taxonomy. Dick's legacy lives on in the hundreds of students from across the globe who learned mosquito identification skills from this world-renowned mosquito taxonomist. All will proudly profess that, "I learned mosquito identification from Dr. Darsie." And that is all that is needed to prove one's credentials in the field, learning the art from the best there is. PMID- 26675473 TI - Unraveling the interplay between hydrogen bonding and rotational energy barrier to fine-tune the properties of triazine molecular glasses. AB - Mexylaminotriazine derivatives form molecular glasses with outstanding glass forming ability (GFA), high resistance to crystallization (glass kinetic stability, GS), and a glass transition temperature (Tg) above room temperature that can be conveniently modulated by selection of the headgroup and ancillary groups. A common feature of all these compounds is their secondary amino linkers, suggesting that they play a critical role in their GFA and GS for reasons that remain unclear because they can simultaneously form hydrogen (H) bonds and lead to a high interconversion energy barrier between different rotamers. To investigate independently and better control the influence of H bonding capability and rotational energy barrier on Tg, GFA and GS, a library of twelve analogous molecules was synthesized with different combinations of NH, NMe and O linkers. Differential scanning calorimetry (DSC) revealed that these compounds form, with a single exception, kinetically stable glasses with Tg values spanning a very broad range from -25 to 94 degrees C. While variable temperature infrared spectroscopy combined to chemometrics reveals that, on average, around 60% of the NH groups are still H-bonded as high as 40 degrees C above Tg, critical cooling rates obtained by DSC clearly show that molecules without H-bond donating linkers also present an outstanding GFA, meaning that H bonding plays a dominant role in controlling Tg but is not required to prevent crystallization. It is a high interconversion energy barrier, provoking a distribution of rotamers, that most efficiently promotes both GFA and resistance to crystallization. These new insights pave the way to more efficient glass engineering by extending the possible range of accessible Tg, allowing in particular the preparation of homologous glass-formers with high GS at ambient temperature in either the viscous or vitreous state. PMID- 26675472 TI - Decoding Sensorimotor Rhythms during Robotic-Assisted Treadmill Walking for Brain Computer Interface (BCI) Applications. AB - Locomotor malfunction represents a major problem in some neurological disorders like stroke and spinal cord injury. Robot-assisted walking devices have been used during rehabilitation of patients with these ailments for regaining and improving walking ability. Previous studies showed the advantage of brain-computer interface (BCI) based robot-assisted training combined with physical therapy in the rehabilitation of the upper limb after stroke. Therefore, stroke patients with walking disorders might also benefit from using BCI robot-assisted training protocols. In order to develop such BCI, it is necessary to evaluate the feasibility to decode walking intention from cortical patterns during robot assisted gait training. Spectral patterns in the electroencephalogram (EEG) related to robot-assisted active and passive walking were investigated in 10 healthy volunteers (mean age 32.3+/-10.8, six female) and in three acute stroke patients (all male, mean age 46.7+/-16.9, Berg Balance Scale 20+/-12.8). A logistic regression classifier was used to distinguish walking from baseline in these spectral EEG patterns. Mean classification accuracies of 94.0+/-5.4% and 93.1+/-7.9%, respectively, were reached when active and passive walking were compared against baseline. The classification performance between passive and active walking was 83.4+/-7.4%. A classification accuracy of 89.9+/-5.7% was achieved in the stroke patients when comparing walking and baseline. Furthermore, in the healthy volunteers modulation of low gamma activity in central midline areas was found to be associated with the gait cycle phases, but not in the stroke patients. Our results demonstrate the feasibility of BCI-based robotic assisted training devices for gait rehabilitation. PMID- 26675474 TI - Alignments? X-ray Diversions, Haptics, Credibility--With a 'Bone-Setting' Clinic in Hyderabad City. AB - In this article, I engage with the diversions of technologies conventionally used for diagnostic scanning among practitioners who perform fracture-reduction and related manual interventions around bodily pain, ostensibly outside the mainstream orthopedic sector, in the city of Hyderabad, south central India. I attend to the performative dimensions of a technology-practice assemblage, and show how enactments of fracture reduction as viable and credible, targeted at establishment orthopedic surgeons, have been enabled through a distributive agency, afforded by scanning technologies. The use of X-rays and other medical scanning technologies by nonbiomedical practitioners have not displaced haptic and other technics of embodied knowledge, but they have been mobilized in order to create wider recognition of the practitioners' skills. This is a process in which a new configuration of medical practice is constituted. PMID- 26675475 TI - Subcritical Water Hydrolysis Effectively Reduces the In Vitro Seeding Activity of PrPSc but Fails to Inactivate the Infectivity of Bovine Spongiform Encephalopathy Prions. AB - The global outbreak of bovine spongiform encephalopathy (BSE) has been attributed to the recycling of contaminated meat and bone meals (MBMs) as feed supplements. The use of MBMs has been prohibited in many countries; however, the development of a method for inactivating BSE prions could enable the efficient and safe use of these products as an organic resource. Subcritical water (SCW), which is water heated under pressure to maintain a liquid state at temperatures below the critical temperature (374 degrees C), exhibits strong hydrolytic activity against organic compounds. In this study, we examined the residual in vitro seeding activity of protease-resistant prion protein (PrPSc) and the infectivity of BSE prions after SCW treatments. Spinal cord homogenates prepared from BSE-infected cows were treated with SCW at 230-280 degrees C for 5-7.5 min and used to intracerebrally inoculate transgenic mice overexpressing bovine prion protein. Serial protein misfolding cyclic amplification (sPMCA) analysis detected no PrPSc in the SCW-treated homogenates, and the mice treated with these samples survived for more than 700 days without any signs of disease. However, sPMCA analyses detected PrPSc accumulation in the brains of all inoculated mice. Furthermore, secondary passage mice, which inoculated with brain homogenates derived from a western blotting (WB)-positive primary passage mouse, died after an average of 240 days, similar to mice inoculated with untreated BSE-infected spinal cord homogenates. The PrPSc accumulation and vacuolation typically observed in the brains of BSE-infected mice were confirmed in these secondary passage mice, suggesting that the BSE prions maintained their infectivity after SCW treatment. One late-onset case, as well as asymptomatic but sPMCA-positive cases, were also recognized in secondary passage mice inoculated with brain homogenates from WB negative but sPMCA-positive primary passage mice. These results indicated that SCW-mediated hydrolysis was insufficient to eliminate the infectivity of BSE prions under the conditions tested. PMID- 26675476 TI - Cells from the skin of patients with systemic sclerosis secrete chitinase 3-like protein 1. AB - BACKGROUND: The chitinase-like protein, Chi3L1, is associated with increased fibrotic activity as well as inflammatory processes. The capacity of skin cells from systemic sclerosis (SSc) patients to produce Chi3L1, and the stimulation of its synthesis by cytokines or growth factors known to be associated with SSc, was investigated. METHODS: Cells were isolated from forearm and/or abdomen skin biopsies taken from SSc patients and normal individuals and stimulated with cytokines and growth factors to assess Chi3L1 expression. Chi3L1-expressing cells were characterized by immunohistochemical staining. RESULTS: Chi3L1 was not secreted by skin cells from normal individuals nor was its synthesis induced by any of the cytokines or growth factors investigated. In contrast, Chi3L1 secretion was induced by OSM or IL-1 in cells from all forearm biopsies of SSc patients, and endogenous secretion in the absence of cytokines was detected in several specimens. Patients with Chi3L1-producing cells at both the arm and abdomen had a disease duration of less than 3 years. Endogenous Chi3L1 production was not a property of the major fibroblast population nor of myofibroblasts, but rather was related to the presence of stem-like cells not present in normal skin. Other cells, however, contributed to the upregulation of Chi3L1 by OSM. CONCLUSIONS: The emergence of cells primed to respond to OSM with increased Chi3L1 production appears to be associated with pathological processes active in SSc. GENERAL SIGNIFICANCE: The presence of progenitor cells expressing the chilectin Chi3L1 in SSc skin appears to play a role in the initiation of the disease process. PMID- 26675477 TI - The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats. AB - OBJECTIVES: This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. RESULTS: ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. LIMITATION: This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3-/-) mice. CONCLUSIONS: Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. PMID- 26675478 TI - Oblique Positioning of the Stereotactic Frame for Biopsies of Cerebellar and Brainstem Lesions. AB - BACKGROUND: Frame-based stereotactic biopsy has proven to be a safe procedure with a high diagnostic yield for patients. Different supratentorial localizations can easily be accessed by standardized stereotactic approaches. Cerebellar and brainstem lesions, however, are not easy to reach because the positioning of the frame pins often makes it impossible to address the entry point properly. METHODS: By oblique positioning of the frame, cerebellar and brainstem lesions also can easily be accessed to take tissue samples. CONCLUSION: Modification of the standardized positioning of the frame allows for safe and straightforward stereotactic access even to cerebellar and brainstem lesions. PMID- 26675479 TI - From Patchell to Brown: An Evidence-Based Evolution of the Role of Radiotherapy on the Management of Brain Metastases. PMID- 26675480 TI - Comparison of Complications in Patients Receiving Different Types of Intracranial Pressure Monitoring: A Retrospective Study in a Single Center in Switzerland. AB - OBJECTIVE: Intracranial pressure (ICP) monitoring has become "state of the art" in the management protocol for unconscious or sedated patients with intracranial pathologies; however, all current monitoring systems have significant drawbacks. We analyzed the complications of these monitoring devices as well as the risk factors for those complications. METHODS: We reviewed a total of 288 patients with ICP monitoring, i.e., 173 external ventricular drainage (EVD) and/or 123 intraparenchymatous catheters (IPCs). Placement of the IPC or EVD was performed by a standardized protocol according to fixed anatomical landmarks. Infections were diagnosed from positive cerebrospinal fluid cultures, positive devices cultures, and/or fever; hemorrhages were diagnosed by postprocedure computed tomography. RESULTS: Sixteen patients (9.2%) with an EVD and 1 patient (0.8%) with an IPC system experienced an infection (P < 0.01). Factors associated with a greater risk for infections include subarachnoid hemorrhage (10 patients, 9.4%), intraventricular hemorrhage (7 patients, 8.6%), and concomitant catheters (6 patients, 3,5%). Mean monitoring time was 3.9 days (range 1-17 days), with the greatest incidence of infections between day 5 and 11. Intracerebral hemorrhage was seen in 2 patients with EVD and in 1 patient with IPC (P < 0.01). None of these patients needed surgical evacuation of the blood clot. CONCLUSIONS: EVD is an indispensable device in neurosurgery. Unfortunately, it has a significantly high complication rate, mostly in relation to infections. Therefore, the indication of the device used to monitor ICP must be evaluated carefully. The antimicrobial-impregnated external catheter and silver-coated catheters might decrease the problem of infection. PMID- 26675481 TI - Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures. AB - Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and alpha particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for (60)Co gamma irradiation and alpha particle irradiation are compared with the measurements accordingly. The excellent agreement with (60)Co irradiation validates our model in simulating photon irradiation. The general agreement found in alpha particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage. PMID- 26675483 TI - Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts. AB - Increasing fetal hemoglobin (HbF) levels in adult humans remains an active area in hematologic research. Here we explored erythroid-specific LIN28A expression for its effect in regulating gamma-globin gene expression and HbF levels in cultured adult erythroblasts. For this purpose, lentiviral transduction vectors were produced with LIN28A expression driven by erythroid-specific gene promoter regions of the human KLF1 or SPTA1 genes. Transgene expression of LIN28A with a linked puromycin resistance marker was restricted to the erythroid lineage as demonstrated by selective survival of erythroid colonies (greater than 95% of all colonies). Erythroblast LIN28A over-expression (LIN28A-OE) did not significantly affect proliferation or inhibit differentiation. Greater than 70% suppression of total let-7 microRNA levels was confirmed in LIN28A-OE cells. Increases in gamma globin mRNA and protein expression with HbF levels reaching 30-40% were achieved. These data suggest that erythroblast targeting of LIN28A expression is sufficient for increasing fetal hemoglobin expression in adult human erythroblasts. PMID- 26675482 TI - Chronic, not acute, skin-specific inflammation promotes thrombosis in psoriasis murine models. AB - BACKGROUND: Psoriasis patients exhibit an increased risk of atherothrombotic events, including myocardial infarction and stroke. Clinical evidence suggests that psoriasis patients with early onset and more severe disease have the highest risk for these co-morbidities, perhaps due to the extent of body surface involvement, subsequent levels of systemic inflammation, or chronicity of disease. We sought to determine whether acute or chronic skin-specific inflammation was sufficient to promote thrombosis. METHODS: We used two experimental mouse models of skin-specific inflammation generated in either an acute (topical Aldara application onto wild-type C57Bl/6 mice for 5 days) or chronic (a genetically engineered K5-IL-17C mouse model of psoriasiform skin inflammation) manner. Arterial thrombosis was induced using carotid artery photochemical injury (Rose Bengal-green light laser) and carotid artery diameters were measured post-clot formation. We also examined measures of clot formation including prothrombin (PT) and activated partial thromboplastin time (aPTT). Skin inflammation was examined histologically and we profiled plasma-derived lipids. The number of skin-draining lymph-node (SDLN) and splenic derived CD11b(+)Ly6C(high) pro-inflammatory monocytes and CD11b(+)Ly6G(+) neutrophils was quantified using multi-color flow cytometry. RESULTS: Mice treated with topical Aldara for 5 days had similar carotid artery thrombotic occlusion times to mice treated with vehicle cream (32.2 +/- 3.0 vs. 31.4 +/- 2.5 min, p = 0.97); in contrast, K5-IL-17C mice had accelerated occlusion times compared to littermate controls (15.7 +/- 2.1 vs. 26.5 +/- 3.5 min, p < 0.01) while carotid artery diameters were similar between all mice. Acanthosis, a surrogate measure of inflammation, was increased in both Aldara-treated and K5-IL-17C mice compared to their respective controls. Monocytosis, defined as elevated SDLN and/or splenic CD11b(+)Ly6C(high) cells, was significantly increased in both Aldara-treated (SDLN: 3.8-fold, p = 0.02; spleen: 2.0-fold, p < 0.01) and K5-IL-17C (SDLN: 3.4 fold, p = 0.02; spleen: 3.5-fold, p < 0.01) animals compared to controls while neutrophilia, defined as elevated SDLN and/or splenic CD11b(+)Ly6G(+) cells, was significantly increased in only the chronic K5-IL-17C model (SDLN: 11.6-fold, p = 0.02; spleen: 11.3-fold, p < 0.01). Plasma-derived lipid levels, PT and aPTT times showed no difference between the Aldara-treated mice or the K5-IL-17C mice and their respective controls. CONCLUSIONS: Chronic, but not acute, skin-specific inflammation was associated with faster arterial thrombotic occlusion. Increased numbers of splenic and SDLN monocytes were observed in both acute and chronic skin-specific inflammation, however, increased splenic and SDLN neutrophils were observed only in the chronic skin-specific inflammation model. Understanding the cellular response to skin-specific inflammation may provide insights into the cellular participants mediating the pathophysiology of major adverse cardiovascular events associated with psoriasis. PMID- 26675485 TI - Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital. AB - BACKGROUND: Cardiovascular diseases (CVD) are one of the leading causes of non communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. AIM: To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. SETTINGS AND DESIGN: Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. MATERIALS AND METHODS: All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. STATISTICAL ANALYSIS USED: The study used descriptive statistics and the values were expressed in numbers and percentages. RESULTS: During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo's scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be enalapril (17.5%), atorvastatin (14.9%), aspirin (8.4%) and metoprolol (8.4%). CONCLUSION: The cardiovascular drug related adverse effects constituted 18.1% of the total ADRs reported during the study period. Cough, gastritis, fatigue and myalgia by enalapril, aspirin, beta blockers and atorvastatin respectively were found to be the most commonly reported ADRs among the cardiovascular drugs. PMID- 26675484 TI - The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. AB - BACKGROUND: The receptor tyrosine kinase (RTK) EGFR is overexpressed and mutated in NSCLC. These mutations can be targeted by RTK inhibitors (TKIs) such as erlotinib. Chromatin-modifying agents may offer a novel therapeutic approach by sensitizing tumor cells to TKIs. METHODS: The NSCLC cell lines HCC827 (EGFR mutant, adenocarcinoma), A549 (EGFR wt, adenocarcinoma) and NCI-H460 (EGFR wt, large cell carcinoma) were analyzed by SNP6.0 array. Changes in proliferation after panobinostat (LBH-589, PS) and erlotinib treatment were quantified by WST-1 assay and apoptosis by Annexin V/7-AAD flow cytometry. Abundance of target proteins and histone marks (acH3, H3K4me1/2/3) was determined by immunoblotting. RESULTS: As expected, the EGFR wt cell lines A549 and NCI-H460 were quite insensitive to the growth-inhibitory effect of erlotinib (IC50 70-100 MUM), compared to HCC827 (IC50<0.02 MUM). All three cell lines were sensitive to PS treatment (IC50: HCC827 10 nM, A549 20 nM and NCI-H460 35 nM). The combination of both drugs further reduced proliferation in HCC827 and in A549, but not in NCI H460. PS alone induced differentiation and expression of p21WAF1/CIP1 and p53 and decreased CHK1 in all three cell lines, with almost no further effect when combined with erlotinib. In contrast, combination treatment additively decreased pEGFR, pERK and pAKT in A549. Both drugs synergistically induced acH3 in the adenocarcinoma lines. Surprisingly, we also observed induction of H3K4 methylation marks after erlotinib treatment in HCC827 and in A549 that was further enhanced by combination with PS. CONCLUSION: PS sensitized lung adenocarcinoma cells to the antiproliferative effects of erlotinib. In these cell lines, the drug combination also had a robust, not previously described effect on histone H3 acetylation and H3K4 methylation. PMID- 26675486 TI - Identification of cis-acting packaging signals in the coding regions of the influenza B virus HA gene segment. AB - For influenza A and B viruses to be infectious, they require eight viral RNA (vRNA) genome segments to be packaged into virions. For efficient packaging, influenza A viruses utilize cis-acting vRNA sequences, containing both non-coding and protein coding regions of each segment. Whether influenza B viruses have similar packaging signals is unknown. Here we show that coding regions at the 3' and 5' ends of the influenza B virus vRNA segment 4 are required for genome packaging, with the first 30 nt at each end essential for this process. Synonymous mutation of these regions led to virus attenuation, an increase in defective particle production and a reduction in packaging of multiple vRNAs. Overall, our data suggest that the influenza B virus vRNA gene segments likely interact with each other during the packaging process, which is driven by cis acting packaging signals that extend into protein coding regions of the vRNA. PMID- 26675487 TI - Joint analysis of extracellular spike waveforms and neuronal network bursts. AB - BACKGROUND: Neuronal networks are routinely assessed based on extracellular electrophysiological microelectrode array (MEA) measurements by spike sorting, and spike and burst statistics. We propose to jointly analyze sorted spikes and detected bursts, and hypothesize that the obtained spike type compositions of the bursts can provide new information on the functional networks. NEW METHOD: Spikes are detected and sorted to obtain spike types and bursts are detected. In the proposed joint analysis, each burst spike is associated with a spike type, and the spike type compositions of the bursts are assessed. RESULTS: The proposed method was tested with simulations and MEA measurements of in vitro human stem cell derived neuronal networks under different pharmacological treatments. The results show that the treatments altered the spike type compositions of the bursts. For example, 6-cyano-7-nitroquinoxaline-2,3-dione almost completely abolished two types of spikes which had composed the bursts in the baseline, while bursts of spikes of two other types appeared more frequently. This phenomenon was not observable by spike sorting or burst analysis alone, but was revealed by the proposed joint analysis. COMPARISON WITH EXISTING METHODS: The existing methods do not provide the information obtainable with the proposed method: for the first time, the spike type compositions of bursts are analyzed. CONCLUSIONS: We showed that the proposed method provides useful and novel information, including the possible changes in the spike type compositions of the bursts due to external factors. Our method can be employed on any data exhibiting sortable action potential waveforms and detectable bursts. PMID- 26675488 TI - The Value of Learning about Natural History in Biodiversity Markets. AB - Markets for biodiversity have generated much controversy because of the often unstated and untested assumptions included in transactions rules. Simple trading rules are favored to reduce transaction costs, but others have argued that this leads to markets that favor development and erode biodiversity. Here, I describe how embracing complexity and uncertainty within a tradable credit system for the Red-cockaded Woodpecker (Picoides borealis) creates opportunities to achieve financial and conservation goals simultaneously. Reversing the effects of habitat fragmentation is one of the main reasons for developing markets. I include uncertainty in habitat fragmentation effects by evaluating market transactions using five alternative dispersal models that were able to approximate observed patterns of occupancy and movement. Further, because dispersal habitat is often not included in market transactions, I contrast how changes in breeding versus dispersal habitat affect credit values. I use an individually-based, spatially explicit population model for the Red-cockaded Woodpecker (Picoides borealis) to predict spatial- and temporal- influences of landscape change on species occurrence and genetic diversity. Results indicated that the probability of no net loss of abundance and genetic diversity responded differently to the transient dynamics in breeding and dispersal habitat. Trades that do not violate the abundance cap may simultaneously violate the cap for the erosion of genetic diversity. To highlight how economic incentives may help reduce uncertainty, I demonstrate tradeoffs between the value of tradable credits and the value of information needed to predict the influence of habitat trades on population viability. For the trade with the greatest uncertainty regarding the change in habitat fragmentation, I estimate that the value of using 13-years of data to reduce uncertainty in dispersal behaviors is $6.2 million. Future guidance for biodiversity markets should at least encourage the use of spatially- and temporally-explicit techniques that include population genetic estimates and the influence of uncertainty. PMID- 26675489 TI - A Molecular Chameleon with Fluorescein and Rhodamine Spectroscopic Behaviors. AB - A new class of fluorescein/rhodamine hybrids with two spirolactone rings was reported to exhibit dual-output fluorescent behaviors independently. Isolation and characterization for two diastereomers, trans-RhOH and cis-RhOH, have been made and their X-ray crystal structures determined. In a basic environment, the spirolactone ring on the hydroxyl side will be opened to give a fluorescein-like optical output with the lowest absorptions at 485 and 530 nm emission. On the other hand, a rhodamine-like optical output, i.e., 528 nm absorption and 575 nm emission, will be switched on by a H(+) or a Hg(2+) ion, attributed to the spirolactone ring opening on the amino side. In a methanol-buffer system with different pH values, the corresponding pKa values for the hydroxyl and amino groups were determined as 5.7 and 2.3, respectively. Selective Hg(2+)-sensing properties have also been discussed, and log Ks values of about 3.60 and 3.73 were determined. Confocal microscopic images of Caenorhabditis elegans incubated with RhOH were found to show enhanced fluorescent intensity with a Hg(2+) ion, demonstrating the potential application of RhOH for in vivo biological imaging. PMID- 26675490 TI - Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication. AB - BACKGROUND: Partial duplication of 2p is a rare condition that causes facial anomalies, psychomotor delay, and growth failure. Hypercalcaemia is rare in children. So far, duplication of 2p has never been associated with hypercalcaemia. METHODS: Here, we report a girl with a partial duplication of 2p presenting with moderate to severe hypercalcaemia at the age of 2 years. She also had hypercalciuria, nephrocalcinosis, decreased renal function, and secondary hyperparathyroidism at presentation. She was thoroughly investigated, including genetic testing of the CYP24A1, CASR, ALPL, and NOD2 genes, to determine the cause of hypercalcaemia. RESULTS: 1,25-dihydroxyvitamin D levels were increased. Hypercalcaemia and hypercalciuria responded well to glucocorticoids but not to cinacalcet. Hyperparathyroidism resolved with improving renal function. Apart from the known duplication of 2p, no pathogenic variants were detected in the studied genes. The duplication of 2p contains the PPP3R1 gene, which encodes for the calcineurin B subunit. CONCLUSION: We conclude that partial duplication of 2p can be associated with hypercalcaemia and hypercalciuria and hypothesise that the underlying mechanism is an increased extra-renal, parathyroid hormone-independent 25-hydroxyvitamin D 1alpha-hydroxylase activity, leading to raised amounts of 1,25-dihydroxyvitamin D. The increased enzymatic activity could possibly be caused by calcineurin B subunit-related macrophage stimulation. PMID- 26675491 TI - Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats. AB - The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. PMID- 26675492 TI - Editorial: Challenge for the European Union: Immigrant and Refugee Health. PMID- 26675493 TI - Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus. AB - BACKGROUND: Diabetes mellitus (DM), a metabolic disease, is characterized by impaired fasting glucose levels. Type 2 DM is adult onset diabetes. Long non coding RNAs (lncRNAs) regulate gene expression and multiple studies have linked lncRNAs to human diseases. METHODS: Serum samples obtained from 96 participating veterans at JAH VA were deposited in the Research Biospecimen Repository. We used a two-stage strategy to identify an lncRNA whose levels correlated with T2DM. Initially we screened five serum samples from diabetic and non-diabetic individuals using lncRNA arrays. Next, GAS5 lncRNA levels were analyzed in 96 serum samples using quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff GAS5 for diagnosis of DM. RESULTS: Our results demonstrate that decreased GAS5 levels in serum were associated with diabetes in a cohort of US military veterans. The ROC analysis revealed an optimal cutoff GAS5 value of less than or equal to 10. qPCR results indicated that individuals with absolute GAS5 < 10 ng/MUl have almost twelve times higher odds of having diabetes (Exact Odds Ratio [OR] = 11.79 (95% CI: 3.97, 37.26), p < 0.001). Analysis indicated area under curve (AUC) of ROC of 0.81 with 85.1% sensitivity and 67.3% specificity in distinguishing non-diabetic from diabetic subjects. The positive predictive value is 71.4%. CONCLUSION: lncRNA GAS5 levels are correlated to prevalence of T2DM. GENERAL SIGNIFICANCE: Assessment of GAS5 in serum along with other parameters offers greater accuracy in identifying individuals at-risk for diabetes. PMID- 26675494 TI - Phyto-enhanced remediation of soil co-contaminated with lead and diesel fuel using biowaste and Dracaena reflexa: A laboratory study. AB - In phytoremediation of co-contaminated soil, the simultaneous and efficient remediation of multiple pollutants is a major challenge rather than the removal of pollutants. A laboratory-scale experiment was conducted to investigate the effect of 5% addition of each of three different organic waste amendments (tea leaves, soy cake, and potato skin) to enhance the phytoaccumulation of lead (60 mg kg(-1)) and diesel fuel (25,000 mg kg(-1)) in co-contaminated soil by Dracaena reflexa Lam for a period of 180 day. The highest rate of oil degradation was recorded in co-contaminated soil planted with D. reflexa and amended with soy cake (75%), followed by potato skin (52.8%) and tea leaves (50.6%). Although plants did not accumulate hydrocarbon from the contaminated soil, significant bioaccumulation of lead in the roots and stems of D. reflexa was observed. At the end of 180 days, 16.7 and 9.8 mg kg(-1) of lead in the stems and roots of D. reflexa were recorded, respectively, for the treatment with tea leaves. These findings demonstrate the potential of organic waste amendments in enhancing phytoremediation of oil and bioaccumulation of lead. PMID- 26675495 TI - Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor-positive advanced breast cancer. AB - Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor-positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor-positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID- 26675496 TI - Hereditary Factors in Esophageal Adenocarcinoma. AB - BACKGROUND: The vast majority of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of EAC. Here, we review data from the published literature in order to address the current knowledge on familial EAC. SUMMARY: Although familial EAC comprises a relatively small group of patients, it is a clinically relevant category due to the poor prognosis of this type of cancer. Efforts should be made to identify specific genetic risk factors for familial EAC to enable identification of relatives at risk, since endoscopic surveillance can diagnose preneoplastic or early neoplastic lesions leading to early treatment, with improved outcome. KEY MESSAGE: Although familial EAC comprises a relatively small group of patients, this is a clinically relevant category due to the poor prognosis. Efforts should be made to identify specific genetic risk factors for familial EAC in order to facilitate the identification of other family members with a predisposition for this type of cancer. PRACTICAL IMPLICATIONS: Approximately 7% of BE and EAC cases are considered familial. Age at diagnosis is generally lower for patients with familial EAC as compared to sporadic cases, while other known risk factors for EAC, such as male gender and Caucasian ethnicity, do not differ between the two groups. In several described families with clustering of EAC the pattern of inheritance seems to be consistent with a rare autosomal dominant genetic trait. However, some association has been found with (attenuated) familial adenomatous polyposis, mismatch repair deficiency and recently with the genes MSR1, ASCC1 and CTHRC1. Nevertheless, no specific genetic predisposition has yet been identified. PMID- 26675497 TI - Postpartum Bilateral Sacroiliitis caused by Brucella Infection. AB - Early diagnosis of this septic sacroiliitis is difficult because symptoms are nonspecific during the postpartum period. In this case we dicscuss about a patient with bilateral buttock pain unresolved with painkillers and rest, after an induction delivery. A 31-year-old woman was presented to our clinic on the second week of postpartum period with bilateral buttock pain. She was subfebrile and had no apparent abnormality on her pelvic X-ray. The pain was so severe that she was unable to walk properly. Sacroiliac MRI during the acute episode of pain showed bone marrow oedema and fluid within the bilateral sacroiliac joint. She was found seropositive for brucellosis and the patient completely recovered with antibiotherapy treatment. We stopped our patient from breastfeeding when the Rose Bengal test turned out positive. Brucella sacroiliitis should be considered in puerperium period women when buttock pain and difficulty in walking are present and pain is unresponsive to analgesics. PMID- 26675498 TI - Role of MRCP in Differentiation of Benign and Malignant Causes of Biliary Obstruction. AB - BACKGROUND: Differentiation of the benign and malignant etiology of biliary obstruction is difficult. We studied the diagnostic accuracy of MRCP (Magnetic Resonance Cholangio-pancreatography) in differentiating between benign and malignant causes of biliary obstruction. AIM: To evaluate the role of Magnetic Resonance Cholangio-Pancreatography in differentiating benign from malignant causes of biliary obstruction using surgical, ERCP or histopathological findings as gold standard. MATERIALS AND METHODS: Seventy five patients with clinical and laboratory finding suggestive of biliary obstruction underwent MRI/MRCP. The final diagnosis was based on either surgical findings, histopathology of resected specimen or ERCP findings. Diagnostic effectivity of MRCP was calculated which included sensitivity, specificity and accuracy. Statistical analysis was done by using chi-square test and p value was calculated. RESULTS: Out of 75 cases, there were 54 benign and 21 malignant cases. Mean age of patients with malignant obstruction was more than benign with slight male preponderance. The diagnostic accuracy of MRCP in differentiating benign from malignant biliary obstructive diseases in correlation with surgical, ERCP and histopathological outcome was 93.3%, sensitivity 85.7%, specificity 96.3%. It was found that irregular, asymmetric and long segment narrowing was more common in malignant stricture. CONCLUSIONS: MRCP is the investigation of choice for suspected choledocholithiasis, choledochal cyst and primary sclerosing cholangitis. A benign stricture can be differentiated from a malignant one if it shows regular, symmetric and short segment narrowing. Irregular, asymmetric and long segment narrowing was more commonly found in malignant stricture. PMID- 26675499 TI - The Trapped Medial Meniscus Tear: An Examination Maneuver Helps Predict Arthroscopic Findings. AB - BACKGROUND: Numerous clinical examination maneuvers have been developed to identify meniscus tears of the knee. While meniscus injuries vary significantly in type and severity, no maneuvers have been developed that help to distinguish particular tear characteristics. PURPOSE: This nonconsecutive case series highlights a distinctive clinical finding that correlates with inferiorly displaced flap tears of the medial meniscus that become trapped in the medial gutter of the knee, as identified through magnetic resonance imaging (MRI) and arthroscopy. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Eight patients with trapped medial meniscus tears were identified from a single surgeon's academic orthopaedic sports medicine practice between January 2009 and January 2012. Each patient underwent clinical evaluation, MRI, and arthroscopic treatment for meniscus injury. Clinical notes, MRI images, radiology reports, and operative findings were reviewed and compared in a descriptive fashion. RESULTS: Each patient displayed a positive clinical examination finding of medial knee pain inferior to the joint line with flexion and the application of valgus stress in the setting of a torn medial meniscus and intact medial collateral ligament (MCL). Preoperative MRI revealed a distinctive flap tear of the medial meniscus flipped inferiorly to lay trapped between the tibia and deep fibers of the MCL. On arthroscopy, flap tears were found displaced inferiorly and trapped in the medial gutter in 6 of the 8 patients. Displaced meniscal fragments in the remaining 2 patients were found within the medial compartment. CONCLUSION: Inferiorly displaced flap tears of the meniscus that have been displaced to the medial gutter can be localized through a careful examination technique. CLINICAL RELEVANCE: Early identification of this injury pattern may help reduce the likelihood that the trapped fragment will be missed during arthroscopy. PMID- 26675500 TI - Diastereoseletive Transannular Oxa-Conjugate Addition Generates the 2,6-cis Disubstituted Tetrahydropyran of Neopeltolide. AB - Transannular 2,6-disubstituted pyrans, like the one found in the cytotoxic marine natural product neopeltolide, are a key functional group in many polyketides. While oxa-conjugate additions have been shown to provide direct and rapid access to tetrahydropyrans in acyclic neopeltolide intermediates, a transannular strategy for construction of this ring system in a macrocyclic core has not been investigated. In this study, we demonstrate that a transannular oxa-conjugate addition strategy is a viable approach to the construction of the bicyclic core of neopeltolide. We show that transannular addition occurs readily with an alpha,beta-unsaturated ketone as the Michael acceptor and does not occur when an alpha,beta-unsaturated ester is the Michael acceptor. Our data indicates that oxa conjugate addition is reversible and that the stereochemical outcome can be under thermodynamic control. Using computational chemistry, we show that the lowest energy diastereomer is the desired cis-pyran found in neopeltolide, and we experimentally demonstrate that the trans and cis diastereomers are interconvertible under reaction conditions with the cis-pyran product predominating. This oxa-conjugate addition strategy should provide a viable route to accessing the fully elaborated macrocyclic core of neopeltolide. PMID- 26675502 TI - Recurrent gastric neuroendocrine tumors treated with total gastrectomy. AB - Gastric neuroendocrine tumors are rare; however, the incidence has recently increased due to the increasing use of upper endoscopy. Neuroendocrine tumors arise from the excess proliferation of enterochromaffin-like (ECL) cells. The proliferative changes of enterochromaffin cells evolve through a hyperplasia dysplasia-neoplasia sequence that is believed to underlie the pathogenesis of gastric neuroendocrine tumors. Endoscopic resection is recommended as the initial treatment if the tumor is not in an advanced stage. However, there is no definite guideline for the treatment of recurrent gastric neuroendocrine tumors following endoscopic resection. Here, we report a rare case of gastric neuroendocrine tumors in a 56-year-old male who experienced two recurrences within 11 years after endoscopic resection. The patient finally underwent a total gastrectomy. The pathological features of the resected stomach exhibited the full hyperplasia dysplasia-neoplasia sequence of the ECL cells in a single specimen. PMID- 26675503 TI - A review of cognitive conflicts research: a meta-analytic study of prevalence and relation to symptoms. AB - Recent research has highlighted the role of implicative dilemmas in a variety of clinical conditions. These dilemmas are a type of cognitive conflict, in which different aspects of the self are countered in such a way that a desired change in a personal dimension (eg, symptom improvement) may be hindered by the need of personal coherence in another dimension. The aim of this study was to summarize, using a meta-analytical approach, the evidence relating to the presence and the level of this conflict, as well as its relationship with well-being, in various clinical samples. A systematic review using multiple electronic databases found that out of 37 articles assessed for eligibility, nine fulfilled the inclusion criteria for meta-analysis. Random effects model was applied when computing mean effect sizes and testing for heterogeneity level. Statistically significant associations were observed between the clinical status and the presence of dilemmas, as well as level of conflict across several clinical conditions. Likewise, the level of conflict was associated with symptom severity. Results highlighted the clinical relevance and the transdiagnostic nature of implicative dilemmas. PMID- 26675504 TI - Standards of the Polish Ultrasound Society - Update. Ultrasound examination of renal arteries. AB - This paper has been prepared on the basis of the Standards of the Polish Ultrasound Society and updated based on the latest reports from the relevant literature. The author presents a renal artery examination technique, patient preparation for the testing, limitations of the method, currently recommended proper blood flow standards and criteria for the diagnosis of significant stenoses. Renal artery ultrasound is performed using a 2-5 MHz probe, usually a convex 3.5 MHz one. The ultrasound machine must be equipped with the Doppler options for the evaluation of color coded blood flow and recording of the blood flow spectrum, including the triplex Doppler mode. Patients have to fast for at least eight hours before testing. Ultrasound always begins with the assessment of renal structure using the grayscale. Next, color coded blood flow imaging is used, followed by placing a sampling gate in the lumen of the target vessel to record the spectral image. The aim of renal artery ultrasound is to assess the course and position of arteries, evaluate blood flow parameters, as well as visualize possible changes: stenoses, occlusions, aneurysms, or arteriovenous fistulas. Blood flow velocity is always measured in a longitudinal projection/ longitudinal section of the vessel, after placing the sampling gate in the central part of the flowing bloodstream, which normally corresponds to the central part of the vascular cross-section. When diagnosing renal artery stenosis, it is necessary to know the nature of the blood flow and norms for flow parameters in healthy vessels. The spectrum of the blood flow velocity in renal arteries and their branches is a low resistance one. The following parameters are used to evaluate normal renal arteries and to identify the narrowed ones: Vmax, Vmin, RAR, AT, AI, RI and PI. PMID- 26675501 TI - Modulation of Protein-Protein Interactions for the Development of Novel Therapeutics. AB - Protein-protein interactions (PPIs) underlie most biological processes. An increasing interest to investigate the unexplored potential of PPIs in drug discovery is driven by the need to find novel therapeutic targets for a whole range of diseases with a high unmet medical need. To date, PPI inhibition with small molecules is the mechanism that has most often been explored, resulting in significant progress towards drug development. However, also PPI stabilization is gradually gaining ground. In this review, we provide a focused overview of a number of PPIs that control critical regulatory pathways and constitute targets for the design of novel therapeutics. We discuss PPI-modulating small molecules that are already pursued in clinical trials. In addition, we review a number of PPIs that are still under preclinical investigation but for which preliminary data support their use as therapeutic targets. PMID- 26675521 TI - Sonography of pathological changes in the hand. AB - Everyday medical practice shows that most common problems within the hand result from overload, injuries and degeneration. Dorsal side pathologies such as de Quervain's and Wartenberg's disease, intersection syndrome or degenerative lesions of carpometa-carpal joint of the thumb discussed in the paper can be accurately diagnosed and differentiated by means of ultrasound examination. Ultrasound is similarly powerful in detection and grading of traumatic lesions involving extensor tendons and their sagittal bands or the flexor tendons and their pulleys. In the case of carpal tunnel syndrome one can not only visualize the median nerve but also other structures of the tunnel that may cause compression. Similarly ulnar nerve compression within the Guyon's canal can be well evaluated. In cases of nerve trauma one can precisely define the level, and in cases of nerve discontinuity, the distance between stumps can be measured which is important in surgery planning. Often nerve trauma is a sequelae of tendon reconstruction. In such cases scars and nerve entrapment can be depicted. Tumors within a hand are usually benign, of which the most common are ganglia. On ultrasound examination a connection between a ganglion and its source (usually a joint or sheath) can frequently be defined. The relationship of tumors to nerves, tendon sheaths or vessels may suggest their nature. Ultrasound with dynamic tissue assessment is a very valuable adjunct to clinical examination. PMID- 26675505 TI - Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance. AB - Despite major efforts, our knowledge about many brain diseases remains remarkably limited. Epigenetic dysregulation has been one of the few leads toward identifying the causes and potential treatments of psychiatric disease over the past decade. A new positron emission tomography radiotracer, [(11)C]Martinostat, has enabled the study of histone deacetylase in living human subjects. A unique property of [(11)C]Martinostat is its profound brain penetrance, a feature that is challenging to engineer intentionally. In order to understand determining factors for the high brain-uptake of Martinostat, a series of compounds was evaluated in rodents and nonhuman primates. The study revealed the major structural contributors to brain uptake, as well as a more clinically relevant fluorinated HDAC radiotracer with comparable behavior to Martinostat, yet longer half-life. PMID- 26675523 TI - Pressure Ulcer Surveillance in Neurotrauma Patients at a Level One Trauma Centre in India. AB - OBJECTIVES: Pressure ulcers are a multifactorial, prevalent, and preventable morbidity. They cause a burden both financially and emotionally, to the individual, their family and doctor, and to society as a whole. Pressure ulcers are extremely difficult to treat; therefore, prevention is key. METHODS: We started a Wound Care Surveillance Program in 2012 involving nurses, physiotherapists, and doctors. We intended to prevent the occurrence of pressure ulcers, ensure early detection, and facilitate the healing process. The Braden scale was used to stratify patients' risk. The number of patients observed in our study was 2,974 over a one-year period. RESULTS: The pressure sore prevalence was 3.1%. Younger and middle-aged patients were most commonly affected; 27% of these patients did not survive. Mortality was not attributed to the pressure ulcer directly. The most common mode of injury was road traffic accidents. Most of our patients had just a single pressure area affected, most commonly the sacrum. Most patients were managed with debridement and dressings while 12% received surgical treatment. Of those with stage one ulcers, 29% healed completely at two months. In stage two and three patients, 17% and 6% healed in two months, respectively, and this number was zero in stage four patients. CONCLUSION: The Wound Care Surveillance Program has been a very effective strategy for the prevention and management of pressure ulcers. Stage two ulcers were the most common in our setup. Braden scoring, traditionally used to screen these ulcers, can be used as a predictive and prognostic tool to predict healing of pressure ulcers. Poor healing is expected in higher staged ulcers and patients with spinal injury and major solid organ injury and those who need a tracheostomy. Home-based care is not up to mark in our society and accounts for most of the cases in the follow up. PMID- 26675522 TI - Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress. AB - BACKGROUND: HSPB1 belongs to the family of small heat shock proteins (sHSP) that have importance in protection against unfolded protein stress, in cancer cells for escaping drug toxicity stress and in neurons for suppression of protein aggregates. sHSPs have a conserved alpha-crystalline domain (ACD), flanked by variable N- and C-termini, whose functions are not fully understood. Dominant missense variants in HSPB1, locating mostly to the ACD, have been linked to inherited neuropathy. METHODS: Patients underwent detailed clinical and neurophysiologic characterization. Disease causing variants were identified by exome or gene panel sequencing. Primary patient fibroblasts were used to investigate the effects of the dominant defective HSPB1 proteins. RESULTS: Frameshift variant predicting ablation of the entire C-terminus p.(Met169Cfs2*) of HSPB1 and a missense variant p.(Arg127Leu) were identified in patients with dominantly inherited motor-predominant axonal Charcot-Marie-Tooth neuropathy. We show that the truncated protein is stable and binds wild type HSPB1. Both mutations impaired the heat stress tolerance of the fibroblasts. This effect was particularly pronounced for the cells with the truncating variant, independent of heat-induced nuclear translocation and induction of global transcriptional heat response. Furthermore, the truncated HSPB1 increased cellular sensitivity to protein misfolding. CONCLUSION: Our results suggest that truncation of the non conserved C-terminus impairs the function of HSPB1 in cellular stress response. GENERAL SIGNIFICANCE: sHSPs have important roles in prevention of protein aggregates that induce toxicity. We showed that C-terminal part of HSPB1 is critical for tolerance of unfolded protein stress, and when lacking causes axonal neuropathy in patients. PMID- 26675524 TI - Intra-abdominal adhesions in ultrasound. Part II: The morphology of changes. AB - Despite their frequent appearance, intra-abdominal adhesions are rarely the subject of clinical studies and academic discussions. For many years the operators have been trying to reduce such unfavourable consequences of interventions in the abdominal structures. The aim of this article is to present the possibilities of intra-abdominal adhesion diagnostics by means of ultrasound imaging based on authors' own experience and information included in pertinent literature. The anatomy and examination technique of the abdominal wall were discussed in Part I of the article. In order to evaluate intraperitoneal adhesions, one should use a convex transducer with the frequency of 3.5-6 MHz. The article provides numerous examples of US images presenting intra-abdominal adhesions, particularly those which appeared after surgical procedures. The significance of determining their localisation and extensiveness prior to a planned surgical treatment is emphasized. Four types of morphological changes in the ultrasound caused by intra-abdominal adhesions are distinguished and described: visceroperitoneal adhesions, intraperitoneal adhesions, adhesive obstructions as well as adhesions between the liver and abdominal wall with a special form of such changes, i.e. hepatic pseudotumour. Its ultrasound features are as follows:The lesion is localised below the scar in the abdominal wall after their incision.The lesion is localised in the abdominal part of the liver segments III, IV and V.With the US beam focus precisely set, the lack of fascia - peritoneum complex may be noticed. An uneven liver outline or its ventral displacement appears.A hepatic adhesion-related pseudotumour usually has indistinct margins, especially the posterior one, and, gradually, from top to bottom, loses its hypoechogenic nature.In a respiration test, this liver fragment does not present the sliding movement - a neoplastic tumour rarely shows such an effect. The immobility of the liver is a permanent symptom of subdiaphragmatic abscess which needs to be included in the differentiation process.In case of doubts, the suspicious liver area may be examined without the consideration of the scar in the abdominal wall. In the differentiation of visceroperitoneal adhesions, firstly, one needs to exclude the peritoneum infiltration in the course of inflammation and neoplastic spreading, which may be very difficult in patients who have undergone a surgery. Pseudomyxoma peritonei constitutes a source of errors much more rarely. PMID- 26675525 TI - Meso-Molding Three-Dimensional Macroporous Perovskites: A New Approach to Generate High-Performance Nanohybrid Catalysts. AB - Newly designed 3D highly ordered macro/mesoporous multifunctional La1-xCexCoO3 nanohybrid frameworks with a 2D hexagonal mesostructure were fabricated via facile meso-molding in a three-dimensionally macroporous perovskite (MTMP) route. The nanohybrid framework exhibited excellent catalytic activity for methane combustion, which derived from the MTMP providing a larger surface area and pore volume, uniform pore sizes, higher accessible surface oxygen concentration, better low-temperature reducibility, and a unique nanovoid 3D structure. PMID- 26675526 TI - Observation of Dielectrically Confined Excitons in Ultrathin GaN Nanowires up to Room Temperature. AB - The realization of semiconductor structures with stable excitons at room temperature is crucial for the development of excitonics and polaritonics. Quantum confinement has commonly been employed for enhancing excitonic effects in semiconductor heterostructures. Dielectric confinement, which gives rises to much stronger enhancement, has proven to be more difficult to achieve because of the rapid nonradiative surface/interface recombination in hybrid dielectric semiconductor structures. Here, we demonstrate intense excitonic emission from bare GaN nanowires with diameters down to 6 nm. The large dielectric mismatch between the nanowires and vacuum greatly enhances the Coulomb interaction, with the thinnest nanowires showing the strongest dielectric confinement and the highest radiative efficiency at room temperature. In situ monitoring of the fabrication of these structures allows one to accurately control the degree of dielectric enhancement. These ultrathin nanowires may constitute the basis for the fabrication of advanced low-dimensional structures with an unprecedented degree of confinement. PMID- 26675527 TI - Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway. AB - Our recent study demonstrated that an amyloid-beta binding molecule, BTA-EG4, increases dendritic spine number via Ras-mediated signaling. To potentially optimize the potency of the BTA compounds, we synthesized and evaluated an amyloid-beta binding analog of BTA-EG4 with increased solubility in aqueous solution, BTA-EG6. We initially examined the effects of BTA-EG6 on dendritic spine formation and found that BTA-EG6-treated primary hippocampal neurons had significantly increased dendritic spine number compared to control treatment. In addition, BTA-EG6 significantly increased the surface level of AMPA receptors. Upon investigation into the molecular mechanism by which BTA-EG6 promotes dendritic spine formation, we found that BTA-EG6 may exert its effects on spinogenesis via RasGRF1-ERK signaling, with potential involvement of other spinogenesis-related proteins such as Cdc42 and CDK5. Taken together, our data suggest that BTA-EG6 boosts spine and synapse number, which may have a beneficial effect of enhancing neuronal and synaptic function in the normal healthy brain. PMID- 26675528 TI - Mitochondrial ClpP activity is required for cisplatin resistance in human cells. AB - In human cells ClpP and ClpX are imported into the mitochondrial matrix, where they interact to form the ATP-dependent protease ClpXP and play a role in the mitochondrial unfolded protein response. We find that reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin, a widely used anti-cancer drug. Conversely, overexpression of HClpP desensitizes cells to cisplatin. Overexpression of inactive HClpP-S97A had no effect. Cisplatin resistance correlated with decreased cellular accumulation of cisplatin and decreased levels of diguanosine-cisplatin adducts in both mitochondrial and genomic DNA. In contrast, higher levels of cisplatin-DNA adducts were found in cells in which HClpP had been depleted. Changes in the levels of ClpP had no effect on the levels of CTR1, a copper transporter that contributes to cisplatin uptake. However, the levels of ATP7A and ATP7B, copper efflux pumps that help eliminate cisplatin from cells, were increased when HClpP was overexpressed. HClpP levels were elevated in cervical carcinoma cells (KB CP20) and hepatoma cells (BEL-7404-CP20) independently selected for cisplatin resistance. The data indicate that robust HClpXP activity positively affects the ability of cells to efflux cisplatin and suggest that targeting HClpP or HClpX would offer a novel mechanism for sensitizing cancer cells to cisplatin. PMID- 26675529 TI - Cytoskeleton deregulation and impairment in amino acids and energy metabolism in early atherosclerosis at aortic tissue with reflection in plasma. AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally, being atherosclerosis the main cause. Main risk factors are known and current effort is very much dedicated to improve prevention. However, the asymptomatic and silent course of atherosclerosis hampers an accurate and individualized risk evaluation. OBJECTIVES: Here we investigate subjacent molecular changes taking place in arterial tissue which can be ultimately translated in a measurable fingerprint in plasma. METHODS: First, we applied a combined approach to find out main molecular alterations at protein and metabolite level in response to early atherosclerosis development in a rabbit model. A potential reflection of all these alterations observed in aortic tissue was investigated in rabbit plasma and further analyzed in a translational study in human plasma from 62 individuals. RESULTS: Data link the structural remodeling taking place in atherosclerotic arteries in terms of loss of contractile properties and favored cellular migration, with an up-regulation of integrin linked kinase, tropomyosin isoform 2 and capping protein gelsolin-like, and a down-regulation of vinculin. A molecular response to oxidative stress is evidenced, involving changes in the glucose metabolism enzymes pyruvate kinase (PKM) and phosphoglycerate kinase (PGK), and pyruvate. Up-regulation of aspartate connects different changes observed in amino acid metabolism and, additionally, alterations in the phosphatidylcholine route of the glycerophospholipid metabolism were found. CONCLUSIONS: A specific molecular marker panel composed by PKM, valine and pyruvate is shown here linked to cardiovascular risk. PMID- 26675530 TI - The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part I: The diagnostic value of the ultrasound B mode imaging in the differentiation diagnostics of solid, focal lesions in the breast in relation to the pathomorphological verification. AB - The aim of this study was to evaluate the diagnostic value of the ultrasound B mode imaging in the differentiation diagnostics of solid lesions in the breast in relation to the pathomorphological verification. From January to July 2010, 375 ultrasound breast examinations were conducted. The study enrolled 80 women aged 17-83, with 99 solid, focal lesions present in breasts, which were qualified for pathomorphological verification on the basis of the ultrasound examination. All patients underwent: the interview, physical examination, ultrasound examination and sonoelastography. The ultrasound features of the lesions, their vascularization patterns in the Doppler examination as well as the adjacent tissues were determined. Next, the focal lesions were categorized according to the BIRADS-US classification. The obtained results were analyzed statistically. In the group of 80 patients, 99 focal, solid lesions in breasts were visualized, including 39 neoplastic, malignant lesions (group I) and 60 lesions of benign nature (group II). The malignant lesions were often characterized by: greater size, irregular shape (34/39), prevalence of the anteroposterior dimension over the lateral-lateral dimension (22/39), acoustic shadowing (20/39), the margins not well-circumscribed (37/39), spiculated margins (16/39) and the presence of calcifications (14/39). The benign lesions were much more often hyper- and isoechogenic (14/60). In group I the lesions more often demonstrated the features of increased vascularization (29/39) and the presence of irregularly shaped vessels (23/29). This vascularization more often originated in the adjacent tissues. In the surroundings of the malignant neoplastic lesions, the presence of edema (16/39) and skin thickening (6/39) occurred more frequently and the abnormal axillary lymph nodes were more often diagnosed. The lesions of group I were assigned to the following BIRADS categories: BIRADS-US 4 (9 lesions) and BIRADS-US 5 (30 lesions). In group II, there was a prevalence of BIRADS-US 3 and 4 categories (58 lesions) and 2 lesions were classified to BIRADS-US 5 category. In the statistical analysis of the models based on BIRADS classification, it was demonstrated that BIRADS 4 showed the highest sum of sensitivity and specificity values of 173.6% in differentiation of the character of focal lesions in the breast (sensitivity 76.92%, specificity 96.67%). PMID- 26675531 TI - Images in Anesthesiology: A Case of Mistaken Atrial Myxoma. PMID- 26675532 TI - G-protein-gated Inwardly Rectifying Potassium Channels Modulate Respiratory Depression by Opioids. AB - BACKGROUND: Drugs acting on MU-opioid receptors (MORs) are widely used as analgesics but present side effects including life-threatening respiratory depression. MORs are G-protein-coupled receptors inhibiting neuronal activity through calcium channels, adenylyl cyclase, and/or G-protein-gated inwardly rectifying potassium (GIRK) channels. The pathways underlying MOR-dependent inhibition of rhythmic breathing are unknown. METHODS: By using a combination of genetic, pharmacological, and physiological tools in rodents in vivo, the authors aimed to identify the role of GIRK channels in MOR-mediated inhibition of respiratory circuits. RESULTS: GIRK channels were expressed in the ventrolateral medulla, a neuronal population regulating rhythmic breathing, and GIRK channel activation with flupirtine reduced respiratory rate in rats (percentage of baseline rate in mean +/- SD: 79.4 +/- 7.4%, n = 7), wild-type mice (82.6 +/- 3.8%, n = 3), but not in mice lacking the GIRK2 subunit, an integral subunit of neuronal GIRK channels (GIRK2, 101.0 +/- 1.9%, n = 3). Application of the MOR agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (DAMGO) to the ventrolateral medulla depressed respiratory rate, an effect partially reversed by the GIRK channel blocker Tertiapin-Q (baseline: 42.1 +/- 7.4 breath/min, DAMGO: 26.1 +/- 13.4 breath/min, Tertiapin-Q + DAMGO: 33.9 +/- 9.8 breath/min, n = 4). Importantly, DAMGO applied to the ventrolateral medulla failed to reduce rhythmic breathing in GIRK2 mice (percentage of baseline rate: 103.2 +/- 12.1%, n = 4), whereas it considerably reduced rate in wild-type mice (62.5 +/- 17.7% of baseline, n = 4). Respiratory rate depression by systemic injection of the opioid analgesic fentanyl was markedly reduced in GIRK2 (percentage of baseline: 12.8 +/- 15.8%, n = 5) compared with wild-type mice (72.9 +/- 27.3%). CONCLUSIONS: Overall, these results identify that GIRK channels contribute to respiratory inhibition by MOR, an essential step toward understanding respiratory depression by opioids. PMID- 26675533 TI - Sonographic imaging of Spigelian hernias. AB - THE AIM OF THE WORK: was to present clinical material referring to rarely occurring abdominal cavity hernias in semilunar line - Spigelian hernias diagnosed with the help of ultrasound. MATERIAL AND METHODS: In the period from 1995 to 2001 785 anterior abdominal wall hernias were diagnosed including 11 Spigelian hernias (1.4%) diagnosed in 10 patients (7 women and 3 men) aged from 38 to 65 years old (average age 48). Eight patients complained of spastic pain in abdomen, in 5 of them it was accompanied by bloating and sometimes loud peristalsis. All the patients had been observing the mentioned symptoms from 2 to 5 years. Each of them had had colonoscopy and abdominal cavity ultrasound examination performed, some of them even three times. In 3 women with uterine fibroid the uterus was removed which did not eliminate the symptoms. The ultrasound examination of the abdominal integument was performed mainly with the use of linear transducers of the frequency of 7-12 MHz; in obese patients also convex transducers were used (3,5-6 MHz). Each examination of abdominal integument included the assessment of the following areas: linea alba from xiphoid process to pubic symphysis including umbilicus, both semilunar lines from costal margins to pubic bones, and also inguinal areas. Moreover, all types of postoperative scars were examined. Each hernia was assessed in terms of size (the greatest dimension), hernia sac contents, width of the ring and reducibility under the compression of the transducer. Moreover, cough test and Valsalva's maneuver were performed. Generally, the examination was performed in a standing position. RESULTS: In 9 patients hernias were localized unilaterally, in one patient bilaterally. In 7 cases the hernia sac contained small bowel, in 2 cases the preperitoneal and omental fat, and in 2 cases preperitoneal fat only. Eight patients presenting with clinical symptoms underwent operative repair. CONCLUSION: Ultrasound examination is beneficial in confirming the diagnosis of Spigelian hernias especially in terms of proper, therapeutic decision-making. PMID- 26675534 TI - Prediction of drug-target interaction by label propagation with mutual interaction information derived from heterogeneous network. AB - The identification of potential drug-target interaction pairs is very important, which is useful not only for providing greater understanding of protein function, but also for enhancing drug research, especially for drug function repositioning. Recently, numerous machine learning-based algorithms (e.g. kernel-based, matrix factorization-based and network-based inference methods) have been developed for predicting drug-target interactions. All these methods implicitly utilize the assumption that similar drugs tend to target similar proteins and yield better results for predicting interactions between drugs and target proteins. To further improve the accuracy of prediction, a new method of network-based label propagation with mutual interaction information derived from heterogeneous networks, namely LPMIHN, is proposed to infer the potential drug-target interactions. LPMIHN separately performs label propagation on drug and target similarity networks, but the initial label information of the target (or drug) network comes from the drug (or target) label network and the known drug-target interaction bipartite network. The independent label propagation on each similarity network explores the cluster structure in its network, and the label information from the other network is used to capture mutual interactions (bicluster structures) between the nodes in each pair of the similarity networks. As compared to other recent state-of-the-art methods on the four popular benchmark datasets of binary drug-target interactions and two quantitative kinase bioactivity datasets, LPMIHN achieves the best results in terms of AUC and AUPR. In addition, many of the promising drug-target pairs predicted from LPMIHN are also confirmed on the latest publicly available drug-target databases such as ChEMBL, KEGG, SuperTarget and Drugbank. These results demonstrate the effectiveness of our LPMIHN method, indicating that LPMIHN has a great potential for predicting drug-target interactions. PMID- 26675535 TI - Perceived Barriers to and Facilitators of Hypertension Management among Underserved African American Older Adults. AB - OBJECTIVE: To understand the perceived barriers to and facilitators of hypertension self-management among underserved African American older adults in a southeastern clinic. DESIGN: Qualitative descriptive. SETTING: Urban cardiovascular health clinic in a southeastern state. PARTICIPANTS: 28 African Americans diagnosed with hypertension. METHODS: Interview questions were focused on knowledge of hypertension management and barriers and facilitators to hypertension self-management. Thematic content analysis was applied. RESULTS: Patients reported increased hypertension knowledge after attending the clinic. All patients reported knowledge of the severe consequences of uncontrolled hypertension. Perceived barriers to hypertension management included lack of money, lack of motivation to exercise, and fear of injury from exercising. Perceived facilitators of hypertension management included weight loss, unexpected diagnosis of hypertension, family members with hypertension and diabetes, and social support. CONCLUSIONS: Findings suggest that perceived barriers and facilitators influence a patient's decision to manage hypertension. Findings suggest the importance of health literacy and patient-provider communication at this particular clinic. Possible factors in the social environment may influence hypertension management. This study adds to the literature by understanding the perceived barriers to and facilitators of hypertension management of an underserved sample in a southeastern clinic. The results suggest a need for the redesign and transformation of future hypertension education strategies aimed at this clinic sample. PMID- 26675536 TI - Analgesia with interfascial continuous wound infiltration after laparoscopic colon surgery: A randomized clinical trial. AB - OBJECTIVES: For major laparoscopic surgery, as with open surgery, a multimodal analgesia plan can help to control postoperative pain. Placing a wound catheter intraoperatively following colon surgery could optimize the control of acute pain with less consumption of opioids and few adverse effects. METHODS: We conducted a prospective, randomized, study of patients scheduled to undergo laparoscopic colon surgery for cancer in Galdakao-Usansolo Hospital from January 2012 to January 2013. Patients were recruited and randomly allocated to wound catheter placement plus standard postoperative analgesia or standard postoperative analgesia alone. A physician from the acute pain management unit monitored all patients for pain at multiple points over the first 48 hours after surgery. The primary outcome variables were verbal numeric pain scale scores and amount of intravenous morphine used via patient controlled infusion. RESULTS: 92 patients were included in the study, 43 had a wound catheter implanted and 49 did not. Statistically significant differences in morphine consumption were observed between groups throughout the course of the treatment period. The mean total morphine consumption at the end of the study was 5.63+/-5.02mg among wound catheter patients and 21. 86+/-17.88mg among control patients (P=.0001). Wound catheter patients had lower pain scale scores than control patients throughout the observation period. No adverse effects associated with the wound catheter technique were observed. The wound catheter group showed lower hospital stays with statistically significant difference (P=.02). CONCLUSIONS: In patients undergoing laparoscopic colon surgery, continuous infusion of local anaesthetics through interfascial wound catheters during the first 48h aftersurgery reduced the level of perceived pain and also reduced parenteral morphine consumption with no associated adverse effects and lower hospital stays. PMID- 26675537 TI - Observation of an atomic exchange bias effect in DyCo4 film. AB - The fundamental important and technologically widely employed exchange bias effect occurs in general in bilayers of magnetic thin films consisting of antiferromagnetic and ferromagnetic layers where the hard magnetization behavior of an antiferromagnetic thin film causes a shift in the magnetization curve of a soft ferromagnetic film. The minimization of the single magnetic grain size to increase the storage density and the subsequent demand for magnetic materials with very high magnetic anisotropy requires a system with high HEB. Here we report an extremely high HEB of 4 Tesla observed in a single amorphous DyCo4 film close to room temperature. The origin of the exchange bias can be associated with the variation of the magnetic behavior from the surface towards the bulk part of the film revealed by X-ray absorption spectroscopy and X-ray magnetic circular dichroism techniques utilizing the bulk sensitive transmission and the surface sensitive total electron yield modes. The competition between the atomic exchange coupling in the single film and the Zeeman interaction lead to an intrinsic exchanged coupled system and the so far highest exchange bias effect HEB = 4 Tesla reported in a single film, which is accommodated by a partial domain wall formation. PMID- 26675539 TI - Review care of dying patients daily, says new NICE guideline. PMID- 26675538 TI - Therapeutic role of endoscopic ultrasound in pancreaticobiliary disease: A comprehensive review. AB - With the development of technology and accessories, the role of endoscopic ultrasound (EUS) has evolved from diagnostics to therapeutics. In order to characterise the therapeutic role of EUS, we searched Web of Knowledge database and reviewed articles associated with therapeutic EUS. There are two modalities for the therapeutic purpose: drainage and fine-needle injection. EUS-guided drainage is a promising procedure for the treatment of peripancreatic fluid collection and biliary obstruction; EUS-guided fine-needle injections such as celiac plexus neurolysis, for the purpose of pain relief for pancreatic cancer and chronic pancreatitis, has emerged as a promising procedure. The aim of the study was to perform a comprehensive and conscientious review on the techniques, complications and clinical outcomes of those EUS-based procedures. PMID- 26675540 TI - Racial Differences in the Effect of Stress on Health and the Moderating Role of Perceived Social Support. AB - OBJECTIVE: The current study examined racial differences in the relationship between late-life stress and health functioning and the moderating role of perceived social support (PSS) in older adults. METHOD: A biracial sample of community-dwelling older adults (65+) from the first two waves of the Duke University's Established Populations for Epidemiologic Studies of the Elderly (EPESE; N = 2,952) was analyzed. Baseline levels of PSS and stress were obtained. Health status was assessed at baseline and follow-up. RESULTS: Analyses revealed a positive effect of PSS on health functioning. There was a three-way interaction among race, stress, and PSS on health functioning. Probing the interaction, for Caucasians, PSS was beneficial at low stress, but not high stress. For African Americans, PSS had a positive effect regardless of stress level. DISCUSSION: PSS is an important protective factor for preserving positive health in late-life; however, benefits may differ by race and intensity of stressor. PMID- 26675541 TI - Improving Health Care for the Future Uninsured in Los Angeles County: A Community Partnered Dialogue. AB - OBJECTIVE: To understand the health care access issues faced by Los Angeles (LA) County's uninsured and residually uninsured after implementation of the Affordable Care Act (ACA) and to identify potential solutions using a community partnered dialogue. DESIGN: Qualitative study using a community-partnered participatory research framework. SETTING: Community forum breakout discussion. DISCUSSANTS: Representatives from LA County health care agencies, community health care provider organizations, local community advocacy and service organizations including uninsured individuals, and the county school district. MAIN OUTCOME MEASURES: Key structural and overarching value themes identified through community-partnered pile sort, c-coefficients measuring overlap between themes. RESULTS: Five overarching value themes were identified - knowledge, trust, quality, partnership, and solutions. Lack of knowledge and misinformation were identified as barriers to successful enrollment of the eligible uninsured and providing health care to undocumented individuals. Discussants noted dissatisfaction with the quality of traditional sources of health care and a broken cycle of trust and disengagement. They also described inherent trust by the uninsured in "outsider" community-based providers not related to quality. CONCLUSIONS: Improving health care for the residually uninsured after ACA implementation will require addressing dissatisfaction in safety-net providers, disseminating knowledge and providing health care through trusted nontraditional sources, and using effective and trusted partnerships between community and health care agencies with mutual respect. Community-academic partnerships can be a trusted conduit to discuss issues related to the health care of vulnerable populations. PMID- 26675542 TI - Radioactivity of peat mud used in therapy. AB - The aim of the study was to determine the contents of natural and artificial isotopes in peat mud and to estimate the radiation dose absorbed via skin in patients during standard peat mud treatment. The analysis included 37 samples collected from 8 spas in Poland. The measurements of isotope concentration activity were conducted with the use of gamma spectrometry methods. The skin dose in a standard peat mud bath therapy is approximately 300 nSv. The effective dose of such therapy is considered to be 22 nSv. The doses absorbed during peat mud therapy are 5 orders of magnitude lower than effective annual dose absorbed from the natural radiation background by a statistical Pole (3.5 mSv). Neither therapeutic nor harmful effect is probable in case of such a small dose of ionising radiation. PMID- 26675543 TI - Development and evaluation of a regression-based model to predict cesium-137 concentration ratios for saltwater fish. AB - Data from published studies and World Wide Web sources were combined to develop a regression model to predict (137)Cs concentration ratios for saltwater fish. Predictions were developed from 1) numeric trophic levels computed primarily from random resampling of known food items and 2) K concentrations in the saltwater for 65 samplings from 41 different species from both the Atlantic and Pacific Oceans. A number of different models were initially developed and evaluated for accuracy which was assessed as the ratios of independently measured concentration ratios to those predicted by the model. In contrast to freshwater systems, were K concentrations are highly variable and are an important factor in affecting fish concentration ratios, the less variable K concentrations in saltwater were relatively unimportant in affecting concentration ratios. As a result, the simplest model, which used only trophic level as a predictor, had comparable accuracies to more complex models that also included K concentrations. A test of model accuracy involving comparisons of 56 published concentration ratios from 51 species of marine fish to those predicted by the model indicated that 52 of the predicted concentration ratios were within a factor of 2 of the observed concentration ratios. PMID- 26675545 TI - Detection of macrolide resistant Mycoplasma pneumoniae in England, September 2014 to September 2015. AB - Mycoplasma pneumoniae infection can cause pneumonia, particularly in children. Global increase in macrolide-resistant M. pneumoniae is of concern due to limited therapeutic options. We describe the detection of macrolide resistance-conferring mutations in 9.3% of 43 clinical specimens where M. pneumoniae was detected in England and Wales from September 2014-September 2015. This study aims to impact by highlighting the presence of macrolide resistance in M. pneumoniae positive patients, promoting increased clinical vigilance. PMID- 26675544 TI - A Hypothesis Concerning the Biphasic Dose-response of Tumors to Angiostatin and Endostatin. AB - This manuscript proposes a hypothesis to explain the U-shaped dose-response observed for angiostatin and other high-molecular-weight drugs in various anti cancer bio-assays. The dose-response curves for angiostatin and endostatin (measured as suppression of tumor growth) go through an optimum (i.e., minimum tumor growth) and then becomes less effective at higher doses. The literature suggests that at lower doses the primary action of these high-molecular-weight drugs is to counteract the angiogenic effects of vascular endothelial growth factor (VEGF). To do this, the drugs must pass out of the blood vessel and enter the extra-cellular matrix (ECM) where VEGF induces the growth and fusion of tip cells. Ironically, VEGF actually facilitates access of the drugs to the ECM by making the vascular endothelium leaky. At higher doses, the high-molecular-weight drugs seem to reverse VEGF-induced permeability of the endothelium. Thus, at high dose rates, it is hypothesized that the drugs are not able to enter the ECM and block the angiogenic effects of VEGF there. As a result, high doses of the drugs do not suppress vascularization of the tumor or tumor growth. Moreover, if the permeability of the vessels is suppressed, the VEGF released by the stroma is concentrated in the ECM where it amplifies the angiogenic activity around the tumor. PMID- 26675546 TI - A chemotherapy response classifier based on support vector machines for high grade serous ovarian carcinoma. AB - Long-term outcome of high-grade serous epithelial ovarian carcinoma (HGSOC) remains poor as a result of recurrence and the emergence of drug resistance. Almost all the patients were given the same platinum-based chemotherapy after debulking surgery even though some of them are naturally resistant to the first line chemotherapy. No method could verify this part of patients right after the surgery currently. In this study, we used 156 paraffin-embedded high-grade HGSOC specimens for immunohistochemical analysis with 37 immunology markers, and association between the expression levels of these markers and the chemoresponse were evaluated. A support vector machine (SVM)-based HGSOC prognostic classifier was then established, and was validated by a 95-patient independent cohort. The classifier was strongly predictive of chemotherapy resistance, and divided patients into low- and high-risk groups with significant differences progression free survival (PFS) and overall survival (OS). This classifier may provide a potential way to predict the chemotherapy resistance of HGSOC right after the surgery, and then allow clinicians to make optimal clinical decision for those potentially chemoresistant patients. The potential clinical application of this classifier will benefit those patients with primary drug resistance. PMID- 26675547 TI - IL-6 promotes growth and epithelial-mesenchymal transition of CD133+ cells of non small cell lung cancer. AB - We examined IL-6 effects on growth, epithelial-mesenchymal transition (EMT) process, and metastatic ability of CD133+ and CD133- cell subpopulations isolated from three non-small cell lung cancer (NSCLC) cell lines: A549, H157, and H1299. We developed IL-6 knocked-down and scramble (sc) control cells of A549 and H157 cell lines by lentiviral infection system, isolated CD133+ and CD133- sub populations, and investigated the IL-6 role in self-renewal/growth of these cells. IL-6 showed either an inhibitory or lack of effect in modulating growth of CD133- cells depending on intracellular IL-6 levels, but there was higher self renewal ability of IL-6 expressing CD133+ cells than IL-6 knocked down cells, confirming the promoter role of IL-6 in CD133+ cells growth. We then examined tumor growth of xenografts developed from CD133+ cells of A549IL-6si vs. A549sc cell lines. Consistently, there was retarded growth of tumors developed from A549IL-6si, CD133+ cells compared to tumors originating from A549sc, CD133+ cells. The effect of IL-6 in promoting CD133+ self-renewal was due to hedgehog (Hhg) and Erk signaling pathway activation and higher Bcl-2/Bcl-xL expression. We also investigated whether IL-6 regulates the EMT process of CD133- and CD133+ cells differently. Expression of the EMT/metastasis-associated molecules in IL-6 expressing cells was higher than in IL-6 knocked down cells. Together, we demonstrated dual roles of IL-6 in regulating growth of CD133- and CD133+ subpopulations of lung cancer cells and significant regulation of IL-6 on EMT/metastasis increase in CD133+ cells, not in CD133- cells. PMID- 26675548 TI - WWOX modulates the ATR-mediated DNA damage checkpoint response. AB - For many decades genomic instability is considered one of the hallmarks of cancer. Role of the tumor suppressor WWOX (WW domain-containing oxidoreductase) in DNA damage response upon double strand breaks has been recently revealed. Here we demonstrate unforeseen functions for WWOX upon DNA single strand breaks (SSBs) checkpoint activation. We found that WWOX levels are induced following SSBs and accumulate in the nucleus. WWOX deficiency is associated with reduced activation of ataxia telangiectasia and Rad3-related protein (ATR) checkpoint proteins and increased chromosomal breaks. At the molecular level, we show that upon SSBs WWOX is modified at lysine 274 by ubiquitination mediated by the ubiquitin E3 ligase ITCH and interacts with ataxia telangiectasia-mutated (ATM). Interestingly, ATM inhibition was associated with reduced activation of ATR checkpoint proteins suggesting that WWOX manipulation of ATR checkpoint proteins is ATM-dependent. Taken together, the present findings indicate that WWOX plays a key role in ATR checkpoint activation, while its absence might facilitate genomic instability. PMID- 26675549 TI - Artemin is hypoxia responsive and promotes oncogenicity and increased tumor initiating capacity in hepatocellular carcinoma. AB - Hypoxia has been reported to regulate the cancer stem cell (CSC) population yet the underlying mechanism is poorly characterized. Herein, we show that Artemin (ARTN), a member of the glial cell derived neurotrophic factor family of ligands, is a hypoxia-responsive factor and is essential for hypoxia-induced CSC expansion in hepatocellular carcinoma (HCC). Clinically, elevated expression of ARTN in HCC was associated with larger tumor size, faster relapse and shorter survival. In vitro, HCC cells with forced expression of ARTN exhibited reduced apoptosis, increased proliferation, epithelial-mesenchymal transition (EMT) and enhanced motility. Additionally, ARTN dramatically increased xenograft tumor size and metastasis in vivo. Moreover, ARTN also enhanced tumorsphere formation and the tumor initiating capacity of HCC cells, consequent to expansion of the CD133+ CSC population. ARTN transcription was directly activated by hypoxia-induced factor 1alpha (HIF-1alpha) and hypoxia induced ARTN promoted EMT and increased the CSC population via AKT signaling. We herein identify a novel HIF-1alpha/ARTN axis promoting CSC-like behavior in hypoxic environments which implicates ARTN as a valuable therapeutic target for HCC. PMID- 26675551 TI - CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi's sarcoma associated herpesvirus infected endothelial cells. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up regulation of IL-6 and VEGF. By using a KS-like nude mouse model, we found that targeting CD147 and downstream ADAMTSs significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, targeting CD147 and associated proteins may represent a promising therapeutic strategy against these KSHV-related malignancies. PMID- 26675552 TI - Intravenous ultrasound contrast agents versus other imaging methods in pediatric patients with neoplastic diseases - a comparison. AB - The lack of registration of ultrasound contrast agents for use in patients below the age of 18 is a significant limitation of their usage. Despite this, examinations with the use of contrast agents are conducted in numerous centers, mainly as part of the diagnostic process of vesicoureteral reflux. Examinations after an intravenous administration of contrast agents are conducted rarely. The reason for this is not only the lack of registration, but also the lack of studies on their safety profile in paediatric patients or no guidelines concerning the dosage. It seems that imaging with the use of such agents could help solve certain clinical problems when other diagnostic methods fail. The paper presents selected cases of pediatric patients treated in oncological departments, in whom the examination with the use of ultrasound contrast agents had a considerable influence on the diagnostic and therapeutic process. PMID- 26675553 TI - Is Bone Grafting Necessary in Opening Wedge High Tibial Osteotomy? A Meta Analysis of Radiological Outcomes. AB - PURPOSE: Bone grafting in opening wedge high tibial osteotomy (OWHTO) is still controversial. The purpose of this study is to compare the radiological outcomes of OWHTO with bone graft (autogenous, allogenous, and synthetic bone graft) and those without bone graft. MATERIALS AND METHODS: PubMed, MEDLINE, EMBASE and Cochrane Register of Studies databases were searched using specific inclusion and exclusion criteria for radiological studies involving OWHTO with bone graft and without bone graft groups. All reported delayed union, nonunion and correction loss were analyzed. Data were searched from the time period of January 2000 through July 2014. In addition, a modified Coleman methodology score (CMS) system was used to assess the methodological quality of the included studies. RESULTS: Twenty-five studies with a mean CMS value of 77 (range, 61 to 85 score) were included. In total, 1,841 patients underwent OWHTO using 4 different procedures for bone graft: autobone graft (n=352), allobone graft (n=547), synthetic bone graft (n=541) and no bone graft (n=401). There was a similar tendency for delayed union, nonunion and correction loss rate among the osteotomy space filling methods. CONCLUSIONS: The meta-analysis showed there was a similar tendency for radiological union and correction maintenance among patients undergoing OWHTO regardless of the type of bone in all of the studies. However, the currently available evidence is not sufficient to strongly support the superiority of OWHTO with bone graft to OWHTO without bone graft. PMID- 26675555 TI - Sutureless Patch Angioplasty for Postoperative Pulmonary Artery Stenosis in Congenital Cardiac Surgeries. AB - BACKGROUND: Reconstruction of branch pulmonary arteries (PAs) can be demanding in redo congenital cardiac surgeries. Sutureless patch angioplasty could be a useful method to solve this problem, and we evaluated the feasibility of sutureless patch angioplasty for postoperative PA stenosis in patients who underwent congenital cardiac surgery. METHODS: We retrospectively reviewed 28 patients (19 males and 9 females) who underwent sutureless patch angioplasty for postoperative PA stenosis between November 2004 and April 2015. The median age was 7.3 months (range, 4.3 to 54.7), and the median weight was 7.2 kg (range, 5.3 to 12.2 kg). Right PA angioplasty was performed in 5, left PA angioplasty in 10, and both sides in 13 patients. The most common original diagnosis was hypoplastic left heart syndrome (n = 18 of 28, 64.3%). Concomitant surgeries were the bidirectional cavopulmonary shunt in 24 patients, the Fontan operation in 3, and the Rastelli operation in 1 patient. RESULTS: No operative death occurred. However, 2 late deaths were recorded, and both were unrelated to PA angioplasty. Mean follow-up duration was 60.9 +/- 33.1 months. None of the patients had postoperative bleeding or thrombotic occlusion. No reoperation for PA restenosis was performed, and only 1 patient (3.6%) had a PA balloon angioplasty with a good result 12.9 months after the operation. Echocardiography or computed tomography angiography at the recent follow-up showed good branch PAs in all patients. CONCLUSIONS: Sutureless patch angioplasty for postoperative PA stenosis could simplify PA angioplasty, and be a safe and effective method for PA reconstruction in patients who undergo congenital cardiac surgery. PMID- 26675554 TI - Pharmacological outcomes in juvenile myoclonic epilepsy: Support for sodium valproate. AB - PURPOSE: Juvenile myoclonic epilepsy (JME) is one of the most frequently diagnosed of the idiopathic generalised epilepsy syndromes, but long term outcome data still remain sparse. METHODS: A retrospective audit was undertaken in 186 patients (male: n=78; female: n=108) diagnosed with JME at the Epilepsy Unit at the Western Infirmary in Glasgow, Scotland between July 1981 and July 2012. Median age at treatment start was 16 years (range 13-44), with median follow-up of 14 years (range 2-32). RESULTS: Overall, 171 patients (92%) achieved remission with antiepileptic drug (AED) treatment (median 9.5 years; range 1-31). After discontinuing treatment in 28 patients, only 11 remained seizure-free off medication. Fifteen patients (8%) continued to have seizures despite having tried up to 8 AED regimens: (5 male, 10 female), 7 of whom had psychiatric comorbidities. AEDs most commonly prescribed included sodium valproate (VPA; n=142), lamotrigine (LTG; n=66) and levetiracetam (LEV; n=22). More male patients than female attained remission with their first or second AED schedule (88% versus 56%). More male patients (44%) received VPA than female (31%) overall. Fewer male patients than female received LTG (26% versus 74%) and LEV (22% versus 78%). Of the monotherapies, remission was achieved using VPA (n=74; 52%), LTG (n=21; 32%) and LEV (n=12, 55%). A total of 76 (25%) of AED schedules resulted in intolerable side-effects, including 29 with VPA, 12 with LTG and 4 with LEV. CONCLUSION: Overall, JME showed a high rate of seizure freedom with AED treatment. VPA appeared to be the most effective AED. Women tended to have a worse outcome than men, since they were increasingly less likely to receive VPA. Patients with psychiatric comorbidities also had a poorer prognosis. PMID- 26675556 TI - Green Tea Polyphenol Prevents Diabetic Rats From Acute Kidney Injury After Cardiopulmonary Bypass. AB - BACKGROUND: Acute kidney injury (AKI) is a common complication accompanying cardiopulmonary bypass (CPB) and is independently associated with increased morbidity and death. Diabetes mellitus increases the risk for AKI after CPB. Epigallocatechin-3-gallate (EGCG) is a major component of the polyphenolic fraction of green tea, which possesses cardioprotective activities, as previously reported. We hypothesized that EGCG also possesses a renoprotective effect through its diverse biochemical properties and assessed the effect on renal function after CPB for diabetic rats. METHODS: Goto-Kakizaki rats developing type 2 diabetes mellitus were randomly assigned to one of the following groups: sham (n = 10), CPB (CPB alone, n = 9), or EGCG (CPB + EGCG, n = 10). CPB was conducted for 30 minutes at a flow rate of 100 mL/kg/min in the CPB and EGCG groups. Rats assigned to the EGCG group were administrated EGCG solution orally for 2 weeks before CPB. We evaluated renal biochemical or histologic changes at 24 hours after CPB. RESULTS: Compared with the CPB group, the EGCG group exhibited milder tubular injury histologically (p < 0.0001) and reduced expression of kidney injury molecule-1, a biomarker for renal tubular injury (p < 0.0001) and 8 hydroxy-2'-deoxyguanosine (p < 0.01), indicating attenuated oxidant stress. CONCLUSIONS: Preoperative oral administration of EGCG ameliorates AKI in a CPB model of diabetic rats through antioxidative properties. This simple method could be applied in a clinical setting as a prophylactic renal protection against AKI after CPB, especially for high-risk patients with diabetes mellitus. PMID- 26675557 TI - Appraisal of Long-Term Outcomes of Tricuspid Valve Replacement in the Current Perspective. AB - BACKGROUND: We address the differential long-term results of tricuspid valve replacement and late valve-related events among bioprostheses versus mechanical prostheses. METHODS: In a single-institution investigation, we reviewed the patients' prospectively collected data and performed a clinical follow-up. Both the Kaplan-Meier (actuarial) and the competing risks (actual) methodologies were used. RESULTS: Overall, 188 tricuspid valve replacements were performed during 1971 to 2012. In this complex population (reoperations, 48.1%; associated procedures in 71.3%), operative mortality was 27.6% (significantly declining in recent years). A bioprosthesis was used in 82.4%. Follow-up was 10.2 +/- 9.1 years (as long as 37.3 years, or 1,270 patient-years; 91.2% complete). At 15 years, freedom from structural valve deterioration was 93.3% +/- 6.4% (competing risks 94.7 +/- 5.1%) in the mechanical group and 85.2% +/- 5.4% (competing risks 92% +/- 2.9%) in the bioprostheses group (p = 0.19). Freedom from any valve related adverse events was lower among mechanical valves versus bioprostheses (although not statistically significant). Mechanical valves showed significantly lower freedom from thromboembolic events (actuarial 62.3% +/- 14.3% versus 97.7% +/- 1.6%; competing risks 74.1% +/- 10% versus 98% +/- 1.4%; p < 0.001) and earlier adverse events (4.9 +/- 4.5 versus 11.1 +/- 9.4 years) than bioprostheses. There were 11 reoperations for bioprosthetic structural valve deterioration (89.8% and 94.3% actuarial and actual freedom, respectively). CONCLUSIONS: Bioprostheses for tricuspid valve replacement have a very good long term durability. Mechanical valves display earlier and more severe morbidity at follow-up. PMID- 26675558 TI - Relationship Between Antiinflammatory Cytokine Interleukin-10 and Lactate Concentrations in Neonates Undergoing the Arterial Switch Operation. AB - BACKGROUND: The aim of this study was to evaluate the relationship between antiinflammatory cytokine interleukin (IL)-10 production and perioperative lactate concentrations and their impact on postoperative outcomes in neonates undergoing the arterial switch operation (ASO). METHODS: Between August 2010 and August 2012, 80 neonates with transposition of the great arteries (TGA) were enrolled. Serum IL-10 levels were measured immediately before and after cardiopulmonary bypass (CPB) on the first, third, and seventh days. Perioperative clinical data were collected prospectively. RESULTS: Patients underwent the ASO at a median age of 72 hours (4-144 hours). We found that serum IL-10 levels significantly correlated with a prolonged intensive care unit (ICU) length of stay (r = 0.3; p = 0.020) and duration of ventilation (r = 0.3; p = 0.017). Serum IL-10 levels on the first day after the surgical procedure had predictive value for a prolonged ICU stay (defined as an ICU stay >6 days postoperatively) by receiver operator curve analysis, with an area under the receiver operating characteristic (ROC) curve of 0.65 (p = 0.045). Logistic regression modeling indicated that serum lactate level (beta = 2.7; p = 0.027), age at operation (beta = -4.0; p = 0.007), and the nature (autologous or allogeneic) of blood products (beta = -3.5; p = 0.030) used during CPB affected serum IL-10 levels. The strongest predictor of increased IL-10 on the first day after operation was a serum lactate level greater than 3 mmol/L measured after the surgical procedure on admission to the ICU, recording an odds ratio of 15.31. Serum lactate levels after operation and at admission to the ICU positively correlated with a prolonged ICU stay (r = 0.4; p = 0.007). CONCLUSIONS: Elevated lactate levels are associated with increased IL-10 production on the first postoperative day. Excessive production of IL-10 on the first day after the surgical procedure is associated with a prolonged ICU stay. PMID- 26675559 TI - Achieving competence in colonoscopy: Milestones and the need for a new endoscopic curriculum in gastroenterology training. AB - Colonoscopy is considered to be the most effective tool for reducing colorectal cancer (CRC) morbidity and mortality. As a result, certifying trainee competence in the performance of colonoscopy is critical to maximizing CRC screening and prevention efforts. Guidelines on training and accreditation around the world have been revised to emphasize the attainment of milestones in the technical and cognitive skills necessary to perform the procedure. To meet this challenge, new evaluation systems have been developed to measure trainee competence through all aspects of colonoscopy training. These changes stem from increased recognition that procedural numbers alone do not necessarily guarantee trainees' proficiency in the performance of colonoscopy. Variability in endoscopic practice and in CRC screening outcomes also point to deficiencies in the current approach towards colonoscopy instruction. However, technological innovations hold great promise in training endoscopists to perform high quality colonoscopy. Furthermore, potential advances in the use of feedback as a training tool provide new avenues for research. This review summarizes the latest evidence on the effort to define, evaluate and promote the achievement of competence in colonoscopy among trainees. PMID- 26675560 TI - Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel. AB - Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40 year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 * 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, beta-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control. PMID- 26675561 TI - Middle lobe preserving right lower lobectomy with a serratus anterior hammock flap in a patient with previous right upper lobectomy. AB - Increasingly, many patients are diagnosed with a second lung cancer after curative thoracotomy. It is very difficult to manage such patients surgically due to the significant loss of pulmonary function. Especially on the right side, avoiding a completion pneumonectomy may contribute to reducing postoperative functional loss and surgical complications as well as the morbidity of post pneumonectomy syndrome. A technique is needed to prevent torsion of the preserved middle lobe. Following recently published cases utilizing a latissimus dorsi muscle flap, in this case report, we describe the use of the serratus anterior muscle flap as an alternative. PMID- 26675562 TI - Reoperation for aortic homograft failure using an Edwards Intuity valve. AB - We report the case of a 50-year old patient with deterioration of an aortic homograft, who successfully underwent aortic valve replacement using an Edwards Intuity sutureless bioprosthesis. The patient presented with rupture of the cusps and severe calcification of the aortic annulus of the homograft, which prevented us from using a standard bioprosthesis for the replacement. PMID- 26675563 TI - The impact of angiotensin II type 1 receptor antibodies on post-heart transplantation outcome in Heart Mate II bridged recipients. AB - OBJECTIVES: Antibodies targeting angiotensin II type 1 receptor (AT1R) have been associated with malignant hypertension, autoimmune diseases and acute rejection and graft loss in solid organ transplantation. The aim of our study was to assess the impact of anti-AT1R antibodies on survival and incidence of acute cellular rejection (ACR) and pathology antibody-mediated rejection (pAMR) in a population of heart transplant recipients who were bridged to transplantation with a durable mechanical assist device Heart Mate II. METHODS: Sera of 69 consecutive heart transplant recipients transplanted between October 2008 and August 2014 were tested for the presence of angiotensin II type 1 receptor antibodies before Heart Mate II device implantation and at the time of transplantation. Overall survival and post-transplant rejection-free survival were compared between antibody negative and antibody-positive recipients using Kaplan-Meier and log-rank tests. RESULTS: Anti-AT1R antibodies were present in 8 patients (11.6%) before Heart Mate II implantation. During the left ventricular assist device (LVAD) bridging, 44 patients (63.8%) who were initially anti-AT1R antibody-negative became positive, leaving 17 (24.6%) anti-AT1R antibody-negative patients at the time of transplantation for all comparisons. One- and 5-year survival was 88 +/- 8 and 76 +/- 10% for anti-AT1R antibody-negative and 87 +/- 5 and 81 +/- 7% for anti-AT1R antibody-positive patients, respectively (P = 0.582). Freedom from ACR at 1 year was 68 +/- 12% for anti-AT1R-negative and 75 +/- 6% for anti-AT1R-positive recipients (P = 0.218). None of the anti-AT1R-negative patients developed AMR 1 year post-transplantation, whereas freedom from pAMR in anti-AT1R-positive recipients was 98 +/- 2% (P = 0.198). CONCLUSIONS: Our data showed no difference in the overall post-heart transplant survival and freedom from acute cellular and antibody-mediated rejection between anti-AT1R-negative and anti-AT1R-positive recipients. Further research is needed to assess the role of anti-AT1R antibodies in the risk stratification of LVAD-bridged recipients on the post-heart transplantation outcomes. PMID- 26675564 TI - Mid- to long-term outcome comparison of the Medtronic Hancock II and bi-leaflet mechanical aortic valve replacement in patients younger than 60 years of age: a propensity-matched analysis. AB - OBJECTIVE: This study aims to compare mid-long-term clinical outcomes between patients younger than 60 years of age undergoing bioprosthetic and mechanical aortic valve replacement. METHODS: From January 2002 to December 2009, patients younger than 60 years of age who received Medtronic Hancock II porcine bioprostheses were selected and compared with those who received mechanical bi leaflet valves in the aortic position. A stepwise logistic regression propensity score identified a subset of 112 evenly matched patient-pairs. Mid-long-term outcomes of survival, valve-related reoperations, thromboembolic events and bleeding events were assessed. RESULTS: The follow-up was only 95.1% complete. Fourteen measurable variables were statistically similar for the matched cohort. Postoperative in-hospital mortality was 3.6% (bioprosthetic valves) and 2.7% (mechanical valves) (P = 0.700). Survival at 5 and 10 years was 96.3 and 88.7% for patients receiving bioprosthetic valve replacement versus 96.3 and 87.9% for patients receiving mechanical valve replacement (P = 0.860), respectively. At 5 and 10 years after operations, freedom from valve-related reoperation was 97.2 and 94.8% for patients receiving mechanical valve replacement, and 96.3 and 90.2% for patients receiving bioprosthetic valve replacement (P = 0.296), respectively. There was no difference between freedom from thromboembolic events (P = 0.528) and bleeding events (P = 0.128) between the matched groups during the postoperative 10 years. CONCLUSIONS: In patients younger than 60 years of age undergoing aortic valve replacement, mid-long-term survival rate was similar for patients receiving bioprosthetic versus mechanical valve replacement. Bioprosthetic valves were associated with a trend for a lower risk of anticoagulation treatment and did not have significantly greater likelihood of a reoperation. These findings suggest that a bioprosthetic valve may be a reasonable choice for AVR in patients younger than 60 years of age. PMID- 26675565 TI - Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction. AB - BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. CONCLUSIONS Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats. PMID- 26675566 TI - Biomarkers for physical frailty and sarcopenia: state of the science and future developments. AB - Physical frailty and sarcopenia are two common and largely overlapping geriatric conditions upstream of the disabling cascade. The lack of a unique operational definition for physical frailty and sarcopenia and the complex underlying pathophysiology make the development of biomarkers for these conditions extremely challenging. Indeed, the current definitional ambiguities of physical frailty and sarcopenia, together with their heterogeneous clinical manifestations, impact the accuracy, specificity, and sensitivity of individual biomarkers proposed so far. In this review, the current state of the art in the development of biomarkers for physical frailty and sarcopenia is presented. A novel approach for biomarker identification and validation is also introduced that moves from the 'one fits all' paradigm to a multivariate methodology. PMID- 26675567 TI - Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives. AB - Advances in surgical and medical treatments for ovarian cancer have improved prognoses. Platinum drugs in particular are pivotal for the medical treatment of ovarian cancer. However, previous studies have revealed that some histological subtypes, such as clear cell carcinoma, are resistant to medical treatment, including that with platinum drugs. Consequently, the clinical prognosis of advanced clear cell carcinoma is remarkably inferior, primarily because of its chemoresistant behavior. The prevalence of clear cell carcinoma is approximately 5 % in the West, but in Japan, its prevalence is particularly high, at approximately 25 %. Current medical treatments for advanced clear cell carcinoma are difficult to administer, and they have poor efficacy, warranting the development of novel target-based therapies. In this review, we describe medical treatments for clear cell carcinoma and discuss future prospects for therapy. In particular, we focus on the mechanism of platinum resistance in clear cell carcinoma, including the role of annexin A4, one of the most investigated factors of platinum resistance, as well as the mutant genes and overexpressed proteins such as VEGF, PI3K/AKT/mTOR signaling pathway, ARID1A, hepatocyte nuclear factor 1beta, ZNF217. We also review targeted molecular therapeutics for epithelial ovarian cancer and discuss their role in clear cell carcinoma treatment. We review the drugs targeting angiogenesis (bevacizumab, sorafenib, and pazopanib), growth factors (gefitinib, erlotinib, lapatinib, trastuzumab, and AMG479), and signaling pathways (temsirolimus, dasatinib, and imatinib), and other drugs (oregovomab, volociximab, and iniparib). This current review summarizes and discusses the clinical significance of these factors in ovarian clear cell carcinoma as well as their potential mechanisms of action. It may provide new integrative understanding for future studies on their exact role in ovarian clear cell carcinoma. PMID- 26675568 TI - Ocular Surface Squamous Neoplasia (OSSN): A Retrospective Study. AB - BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a term used to describe neoplastic epithelial abnormalities of conjunctiva and cornea, ranging from Squamous Dysplasia to Invasive Squamous Cell Carcinoma. In recent times, the incidence of OSSN seems to be on the rise, especially in developing countries like India. AIM: To analyse demographic characteristics and compare the clinical presentation, treatment outcomes, and histopathology features of Ocular Surface Squamous Neoplasia (OSSN). DESIGN: Retrospective cross-sectional study. MATERIALS AND METHODS: We analysed 113 cases of OSSN who presented to the out-patient department of Sarojini Devi Eye Hospital, Regional Institute of Ophthalmology over a period of three years from February 2012 to January 2015. RESULTS: In patients, who presented with OSSN age ranged from 18 to 78 years, mean age being 45.20 years. Males were predominantly affected accounting for 65.48%. A nodule at the limbus is the commonest presentation. About 23% of the patients tested positive for HIV in whom mean age of presentation was 34 years. Among HIV positive patients 78.26% had SCC. CONCLUSION: Increased incidence of OSSN was observed in males and people with outdoor occupations. Nodular type of lesion is the commonest variety. HIV positive individuals have an increased incidence of OSSN with invasive characteristics. Hence, ophthalmologists need to be aware of this association and a thorough workup is warranted for all patients presenting with OSSN, especially in the younger age group. Our study Also suggests that OSSN may be the first manifestation of underlying HIV infection. PMID- 26675569 TI - [Diagnosis and treatment guideline of hypertensive disorders in pregnancy (2015)]. PMID- 26675570 TI - [Chinese expert consensus on diagnosis and treatment of female genital tract congenital anomalies]. PMID- 26675571 TI - [Analysis of preeclampsia-eclampsia multiple factors and multi-mechanism of pathogenesis to broaden our viewpoint into practice]. PMID- 26675572 TI - [Variation of long-chain 3-hydroxyacyl-CoA dehydrogenase DNA methylation in placenta of different preeclampsia-like mouse models]. AB - OBJECTIVE: By detecting the variation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) DNA methylation in preeclampsia-like mouse models generated by different ways, to explore the roles of multifactor and multiple pathways in preeclampsia pathogenesis on molecular basis. METHODS: Established preeclampsia like mouse models in different ways and divided into groups as follows: (1) Nw nitro-L-arginine-methyl ester (L-NAME) group: wild-type pregnant mouse received subcutaneous injection of L-NAME; (2) lipopolysaccharide (LPS) group: wild-type pregnant mouse received intraperitoneal injection of LPS; (3) apolipoprotein C III (ApoC3) group: ApoC3 transgenic pregnant mouse with dysregulated lipid metabolism received subcutaneous injection of L-NAME; (4) beta2 glycoprotein I (beta-2GPI) group: wild-type pregnant mouse received subcutaneous injection of beta-2GPI. According to the first injection time (on day 3, 11, 16 respectively), the L-NAME, LPS and ApoC3 groups were further subdivided into: pre-implantation (PI) experimental stage, early gestation (EG) experimental stage, and late gestation (LG) experimental stage. beta-2GPI group was only injected before implantation. LCHAD gene methylation levels in placental were detected in different experimental stage. Normal saline control groups were set within wild type and ApoC3 transgenic pregnant mice simultaneously. RESULTS: (1) CG sites in LCHAD DNA: 45 CG sites were detected in the range of 728 bp before LCHAD gene transcription start site, the 5, 12, 13, 14, 15, 16, 19, 24, 25, 27, 28, 29, 30, 31, 32, 34, 35, 43 CG sites were complex sites which contained two or more CG sequences, others were single site which contained one CG sequence. The 3, 5, 6, 11, 13, 14, 18, 28 sites in L-NAME, LPS, ApoC3 and beta-2GPI groups showed different high levels of methylation; the 16, 25, 31, 42, 44 sites showed different low levels of methylation; other 32 sites were unmethylated. (2) Comparison of LCHAD gene methylation between different groups: the methylation levels of LCAHD gene at 3, 11, 13, 14, 18 sites in L-NAME, LPS, ApoC3 and beta 2GPI groups were significantly higher than those in the normal saline control group (P < 0.05); and the methylation levels of 42, 44 sites in these groups were significantly lower than those in the normal saline control group (P < 0.05). (3) Methylation of LCHAD gene at the same site between different experimental stages: 1 The 3, 11, 18 sites of EG experimental stage was significantly lower than PI and LG experimental stage in L-NAME group (P < 0.05); the 3, 11, 18 sites of PI experimental stage was significantly lower than EG and LG experimental stage in LPS group (P < 0.05); these sites of PI experimental stage was significantly higher than EG and LG experimental stages in ApoC3 group (P < 0.05). 2 The methylation of site 5 in L-NAME and LPS groups were significantly higher than that of the normal saline control group (P < 0.05), and the LG experimental stages were significantly higher than other stages, but in ApoC3 group, only PI and EG stages were significantly higher than the normal saline control group (P < 0.05). 3 At site 6 in L-NAME group which showed high methylation level was significantly higher than the same site in other groups which showed low methylation level (P < 0.05). 4 At 13, 14 sites, earlier preeclampsia onset caused a lower methylation level in L-NAME group, but PI experimental stage was significantly higher than EG and LG experimental stages in LPS group (P < 0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P < 0.05). 5 At site 28, earlier preeclampsia onset caused a higher methylation level in L-NAME group, but PI experimental stage was significantly lower than EG and LG experimental stages in LPS group (P < 0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P < 0.05). 6 The 16, 25, 31 sites in ApoC3 group were significantly higher than other groups (P < 0.05). 7 At site 42 in beta-2GPI group was unmethylated, but it in other groups showed low methylation level, the methylation level of site 42 in beta-2GPI group was significantly lower than that in other groups (P < 0.05). CONCLUSIONS: The methylation of 6 and 42 CG sites may be related to LCHAD gene expression in placenta of L-NAME and beta-2GPI induced preeclampsia-like models respectively; LCHAD gene expression and DNA methylation may not have obvious correlation in LPS and ApoC3 induced preeclampsia-like models. Differences exist in LCHAD DNA methylation in preeclampsia-like models generated by different ways, revealed a molecular basis to expand our understanding of the multi-factorial pathogenesis of preeclampsia. PMID- 26675573 TI - [Role of angiogenic T cells and EPC in the pathogenesis of preeclampsia and the relationship between angiogenic T cells and EPC]. AB - OBJECTIVES: To investigate the role of angiogenic T cells (Tang) and endothelial progenitor cells (EPC) in the pathogenesis of preeclampsia. To explore the relationship between Tang and EPC. METHODS: From Mar 2013 to Aug 2014, 40 patients diagnosed preeclampsia (PE) and delivered in Hunan Provincial People's Hospital. A total of 20 of them were defined as the mild preeclampsia group and the other 20 cases were recruited as the severe preeclampsia group. And 24 healthy pregnant women were recruited as the control group. The percentage of Tang and EPC in peripheral blood mononuclear cells (PBMC) were determinated by flow cytometry between 28 and 40 gestational weeks. RESULTS: (1) There was no significant difference in the age, pre-pregnancy body mass index (Pre-BMI) or gestational age among the three groups (P > 0.05). The differences of blood pressure among the three groups were statistically significant (P < 0.05). The gestational week at delivery, the birthweight of the neonates and the 1 minute Apgar score in the severe preeclampsia group were lower than those in the mild preeclampsia group and the control group, with statistically significant differences (P < 0.05). The morbidity of neonatal asphyxia in the severe preeclampsia group was 35% (7/20); and in the mild preeclampsia group it was 5% (1/20), with statistically significant difference (P < 0.05). (2) The percentage of Tang in maternal peripheral blood was (52.7 +/- 8.0)%, (47.5 +/- 8.8)% and (45.5 +/- 8.7)% in the control group, the mild preeclampsia group and the severe preeclampsia group, respectively. The difference among the three groups was significant (F = 4.248, P < 0.05), and SNK q analysis showed there was significant difference between the control group and the severe preeclampsia group (P < 0.05). While there was no statistically significant difference between the mild and the severe preeclampsia group, nor between the control group and the mild preeclampsia group(P > 0.05). (3) The percentage of EPC in maternal peripheral blood was (0.16 +/- 0.07)%, (0.09 +/- 0.07)% and (0.08 +/- 0.05)% in the control group, the mild and the severe preeclampsia group, respectively. Analysis of variance showed that difference among the three groups was significant (F = 9.351, P < 0.05). The percentage of EPC in the mild or the severe preeclampsia group was significantly higher than that of the control group (P < 0.05). (4) There was no statistically significant correlation between the Tang level and the EPC level in the control group (r = -0.325, P > 0.05). In the preeclampsia group (including mild and severe cases), there was positive correlation between the Tang level and EPC level (r = 0.667, P < 0.01). The positive correlation between Tang level and EPC level were proved respectively in the mild preeclampsia group (r = 0.803, P < 0.01) and the severe preeclampsia group (r = 0.520, P < 0.05). CONCLUSIONS: The number of Tang had some correlation with the pathogenesis of preeclampsia. The percentage of Tang had positive correlation with the level of EPC in women with preeclampsia. Tang might have some influence on the change of EPC' level. Tang together with EPC were likely to contribute to the angiogenesis in preeclampsia. PMID- 26675574 TI - [Expression of thrombomodulin in maternal plasma and placental tissue in early onset severe preeclampsia]. AB - OBJECTIVE: To explore the thrombomodulin (TM) expression levels changes in plasma and placenta in patients with early onset severe preeclampsia. METHODS: Sixty cases of severe preeclampsia women who delivered in the affiliated Xuzhou Maternity and Child Health Care Hospital of Xuzhou Medical College were enrolled in the study from June 2012 to February 2014, including 30 patients with early onset severe preeclampsia (early onset group), and 30 patients with late onset severe preeclampsia (late onset group). Healthy pregnant women were divided into two control groups according to gestational weeks at delivery: early control group (n = 23, at 28-33+6 weeks), and late control group (n = 30, delivered after 34 weeks). ELISA was used to detect the levels of TM in plasma. Immunohistochemistry SP was applied to detect the TM protein expression on placenta. TM mRNA was determined by reverse transcription polymerase chain reaction (RT)-PCR technique. RESULTS: (1) TM level in plasma in early onset group and late onset group were (90.8 +/- 6.9) and (87.5 +/- 7.0) ug/L, and TM level in plasma in early control group and late control group were (37.7 +/- 2.3) and (37.7 +/- 2.5) ug/L. Plasma TM level in early onset group was higher than that in late onset group, early control group and late control group. The TM level had no statistically significant compare of early-onset group to late onset group. (P > 0.05). The plasma TM level in early onset group was significantly higher than that in early control group (P < 0.05), and the plasma TM level in late onset group was significantly higher than that in late control group (P < 0.05). (2) TM expressed mainly in the membrane and cytoplasm of placental syncytiotrophoblasts and endothelial cells. The expression of TM protein in early onset group was 47% (14/30), significantly lower than that in late onset group, early control group and late control group (P < 0.05), in which the positive rate were 90% (27/30), 91% (21/23) and 93% (28/30) respectively (P < 0.05). There was no difference between late onset group and late control group (P > 0.05). There was no difference between early control group and late control group (P > 0.05). (3) TM mRNA expression in early onset group, late onset group, early control group and late control group were 0.14 +/- 0.06, 0.89 +/- 0.23, 0.88 +/- 0.22 and 0.93 +/- 0.19, respectively. The expression of TM mRNA in early onset group was significantly lower than that in late onset group, early control group and late control group (P < 0.05), and the difference between early control group and late control group was not statistically significant (P > 0.05). There was no difference between late onset group and late control group (P > 0.05). There was no difference between early control group and late control group (P > 0.05). CONCLUSIONS: Decreased expression of TM in placenta may be associated with the pathogenesis of early onset severe preeclampsia, there may be different pathogenesis in early onset and late onset severe preeclampsia. PMID- 26675575 TI - [Pathologic features of fallopian tubal fimbriae in patients with endometrial serous carcinoma]. AB - OBJECTIVE: To discuss the potential relationship between endometrial serous carcinoma (ESC) and tubal epithelial lesions by pathologic examination of fallopian tubes with ESC. METHODS: A total of 30 cases of typical ESC were reexamined and chosen by the pathologist. In each case, bilateral fallopian tubes were submitted to examination of pathologic morphology and immunostaining for p53, annexin IV (ANX-IV), human epidermal growth factor receptor 2 (HER2)/neu, and high-mobility group protein A2 (HMGA2). RESULTS: Fallopian tubal epithelial lesions were found in 15 cases, including 9 cases tubal serous carcinoma, 2 cases serous tubal intraepithelial carcinoma (STIC) and 2 cases epithelial hyperplasia. Both sides of tubal serous carcinoma and STIC were found in 1 case. The results showed the positive expression for p53 in 26 (87%) out of 30 endometrial malignant specimens tissues and 9 (30%) tubal tissues samples (P > 0.05). Twenty five (83%) endometrial malignant specimens tissues and 6 (20%) tubal tissues samples showed the positive expression of ANX-IV. Twenty-one (70%) endometrial malignant tissues and 7 (23%) tubal tissues showed the positive expression of HER2/neu. Twenty-five (83%) endometrial malignant tissues and 6 (20%) tubal tissues showed the positive expression of HMGA2. While, there were significant differences among the expression of three proteins between endometrium and the fallopian tube site (all P < 0.05). CONCLUSIONS: STIC may be associated with the occurrence of ESC. The expression of p53 was positively correlated between the fallopian tube and the endometrium. ANX-IV, HER2/neu and HMGA2 were extensively expressed in ESC. PMID- 26675576 TI - [Analysis about the high risk factors and prognosis of gynecologic cancer with deep venous thrombosis]. AB - OBJECTIVE: To discuss the risk factors and prognosis of gynecologic cancer patients with deep venous thrombosis (DVT). METHODS: Data from gynecologic cancer patients diagnosed by cytology or histopathology in Affiliated Tumor Hospital of Guangxi Medical University between Jan. 1994 and Sep. 2014 were collected, including 106 cases in the DVT group, according to 1:1 proportion by the computer random method to selecting patients without DVT as the control group. The follow up deadline was March 31, 2015. The median follow-up time of DVT group was 27.0 months (range, 1 to 169 months), while the control group was 33.5 months (range, 1 to 125 months). Univariate analysis was performed by two independent sample t test or chi2 test. Multivariate analysis was performed by logistic regression analysis. The Kaplan-Meier curve was used to estimate the survival analysis. RESULTS: (1) The univariate analysis showed that body mass index (BMI), hypertension, diabetes, history of thrombosis, tumor stage, blood transfusion, stimulating factor, white blood cell (WBC), platelet (PLT), prothrombin time (PT) and fibrinogen (FIB) were statistically significant associated with DVT (P < 0.05). Multivariate analysis showed that tumor stage, stimulating factor, WBC, PT and FIB may be the independent risk factors of gynecologic cancer with DVT (P < 0.05). (2) The median survival time in DVT group was 66 months, while the control group was 102 months (chi2 = 7.039, P = 0.008). The overall survival and progression-free survival in the DVT group were statistically significant lower than those in the control group (P < 0.05). The tumor stage, the scope of DVT (whether with pulmonary embolism) and the treatment of DVT were the effective factors influenced the prognosis of gynecologic oncology patients with DVT (P < 0.05). Cox regression model showed that tumor stage and the scope of DVT were the independent risk factors (P < 0.01). CONCLUSIONS: Gynecologic cancer with DVT is the common effect of various risk factors. We should identify the risk factors for high-risk patients and take preventive measures actively to reduce the deep venous thromboembolism, then improve the survival of patients and their prognosis. PMID- 26675577 TI - [Targeted interruption of COX-2 gene by siRNA inhibits the expression of VEGF, MMP-9, the activity of COX-2 and stimulates the apoptosis in eutopic, ectopic endometrial stromal cells of women with endometriosis]. AB - OBJECTIVE: To investigate the effect of targeted interruption of cyclooxygenase-2 (COX-2) gene by small interference RNA (siRNA) on the expression of COX-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in eutopic and ectopic endometrial stromal cells (ESC) with endometriosis, and the effect on the content of 6-keto-prostaglandin-F1alpha (6-keto-PGF1alpha, metabolites of COX) and the apoptosis of eutopic and ectopic ESC with endometriosis. METHODS: Ectopic and eutopic ESC from 30 women with endometriosis were isolated and cultured respectively. Then, ESC were classified into three groups: interference group, negative control group and blank control group. ESC in interference group were injected into siRNA transfection complex while ESC in negative control group were injected into negative control transfection complex. ESC from 10 participants without endometriosis were the normal control group. The mRNA and protein expression of COX-2, VEGF, MMP-9 in pre-transfected and post transfected eutopic and ectopic ESC were detected through real time reverse transcription PCR and western blot. The content of 6-keto-PGF1alpha was determined by ELISA, the apoptotic cells were detected by flow cytometry. RESULTS: After interruption of COX-2 gene, there were no significant difference in the mRNA and protein expression of COX-2, VEGF and MMP-9 between the negative control group and blank control group (P > 0.05); the mRNA and protein expression of the three genes in interference group were significantly lower than those in negative control group and blank control group (P < 0.05); the mRNA expression of the three genes in interference group of eutopic ESC were 0.87 +/- 0.06, 1.76 +/- 0.59, 1.04 +/- 0.32, in interference group of ectopic ESC were 0.75 +/- 0.12, 1.62 +/- 0.47, 0.88 +/- 0.25, the protein expression of the three genes in interference group of eutopic ESC were 0.457 +/- 0.019, 0.500 +/- 0.012, 0.361 +/ 0.008, in interference group of ectopic ESC were 0.323 +/- 0.018, 0.474 +/- 0.016, 0.339 +/- 0.009; the mRNA and protein expression of the three genes in ectopic ESC had a more reduction than those in eutopic ESC (P < 0.05). The results from ELISA revealed that the content of 6-keto-PGF1alpha in the normal control group [(17.7 +/- 1.9) pg/ml] were significantly lower than those in the blank control group (P < 0.05), the content of 6-keto-PGF1alpha in ectopic ESC were significantly higher than that in eutopic ESC (P < 0.05), the content of 6 keto-PGF1alpha in the blank control group of eutopic and ectopic ESC were (32.4 +/- 2.6) pg/ml, (38.2 +/- 3.7) pg/ml; there was no significant difference in the content of 6-keto-PGF1alpha between the negative control group and blank control group (P > 0.05); compared with those of negative control group and blank control group, the content of 6-keto-PGF1alpha in interference group decreased significantly (P < 0.05), the content of 6-keto-PGF1alpha in interference group of eutopic and ectopic ESC were (17.1 +/- 2.4) pg/ml, (20.9 +/- 2.7) pg/ml; the content of 6-keto-PGF1alpha in eutopic ESC had a slightly more reduction than that in ectopic ESC (P > 0.05). The results from flow cytometry displayed that, there was no significant difference in apoptotic cells between the negative control group and blank control group (P > 0.05); compared with those of negative control group and blank control group, more apoptotic cells were detected in interference group and the difference was significant (P < 0.01); the apoptotic cells in ectopic ESC were significantly more than that in eutopic ESC (P < 0.05); the apoptosis rate in interference group of eutopic and ectopic ESC were (33.76 +/- 0.06)%, (47.18 +/- 0.12)%. CONCLUSIONS: Our results suggested the targeted interruption of COX-2 gene by siRNA effectively inhibited the mRNA and protein expression of COX-2, VEGF and MMP-9 in both eutopic ESC and ectopic ESC with endometriosis, greatly increased the apoptotic rate of cells and obviously reduced the content of 6-keto-PGF1alpha by inhibiting the activity of COX-2. And the changes in ectopic endometrium were more evident than those in eutopic endometrium. PMID- 26675578 TI - Modified sonoelastographic scale score for lymph node assessment in lymphoma - a preliminary report. AB - Elastography is a new method of assessment of lymph node consistency. The majority of papers focus on metastases detection of head and neck or breast tumors. The typical desmoplastic reaction in connective tissue stroma in cancer, which is responsible for tissue's hardening, is seen in lymphoma less frequently. MATERIAL AND METHODS: Study of 15 patients with active Hodgkin and non-Hodgkin lymphomas and 16 previously treated patients with no evidence of recurrence. A total of 60 patients suffering from reactive lymphadenopathy was the control group. The size, appearance, vascularity and elastogram of lymph node was analyzed. RESULTS: Type C elastogram correlated strongly with lymph nodes which presented at least three pathologic features in 2D image. Large lymph nodes with long axis diameter over 3 cm may have 'cheese with holes' appearance rather than common type C elastogram. CONCLUSION: According to our simplified sonoelastography scoring system, type C elastogram was present mainly in patients with active lymphoma affecting lymph nodes, which showed all four features that we analyzed using conventional ultrasonography. This elastogram was also present in reactive lymphadenopathies. Distinctive for large lymph nodes in patients with active forms of lymphoma "cheese with holes" appearance, can be considered as equal with type C image, although it is corresponding to type B sonoelastographic map. PMID- 26675579 TI - Prevalence and risk factors for under nutrition among children under five at Haramaya district, Eastern Ethiopia. AB - BACKGROUND: Under nutrition is one of the major causes of health problems among children under five years old in Ethiopia. Though the problem of under nutrition has decreased in the country, it is still continuing as one of the major causes of mortality of children under five. Studies have shown that the magnitude and related factors of under nutrition are varied in different agro-ecological settings of the country. Thus it is indispensable to assess the nature of the problem at community level. The objective of this study was to assess the extent of under nutrition and related factors among children under five years in Haramaya district, eastern Ethiopia. METHODS: A community based cross sectional study was conducted in Haramaya district from December 1, 2012 to January 30, 2013 and Multi-stage stratified systematic random sampling technique was used to select the study subjects. A total of 791 study subjects were included in the study. Data were collected using face-to-face interview and anthropometric measurements. World Health Organization (WHO) Anthro software was used to convert nutritional data indices from anthropometric measurement into Z-scores, and Multivariate logistic regression model with an enter method was used to determine the predictors of under nutrition. RESULTS: The study indicated that prevalence of stunting, wasting and underweight among children under five years old were 45.8%, 10.7 % and 21 % respectively. Children in rural Kebeles with Adjusted odd ratio (AOR) =2.45, 95% CI(1.25-6.66), children who were 6 and above birth order (AOR =1.992, 95% CI( 1.05-3.77)), and children who were used to live with households having two and more under five children (AOR = 1.81, 95% CI( 1.19 2.7)) were more stunted than their counterparts. Children in the lowland Kebeles, (AOR = 3.29, 95% CI( 1.2-8.8)) and children having diarrhea, (AOR = 2.48, 95% CI(1.28-4.78)); mothers with Body mass index (BMI) < 18.5 (AOR = 2.17, 95% CI(1.17-3.81)); mothers who did not have ANC visit during pregnancy (AOR = 3.47, 95% CI (1.49-7.8) ) and with birth order of 4 to 5 children (AOR = 3.08, 95% CI (1.11-8.5)), were more likely to be underweight than their counterparts. Moreover, male children (AOR = 2.37, 95% CI (1.19-4.7)), children who were served food with family (AOR = 2.3, 95% CI (1.14- 4.9)), children who had fever, (AOR = 2.9, 95% CI (1.16-7.2)), were more likely to be wasted than their counterparts. CONCLUSIONS: This study indicated that nearly half of the children under five years in the study area were stunted. Thus, a large number of children had poor nutritional history or growth failure. Furthermore, underweight and wasting were significantly high. The problem can be addressed by targeting children since their early ages and by conducting tailored nutrition education to mothers or caretakers to improve the nutritional status of their children. PMID- 26675580 TI - Uptake and release of gaseous species accompanying the reactions of isoprene photo-oxidation products with sulfate particles. AB - Gaseous species produced via the HO2 reaction pathways of isoprene photo oxidation were reacted with liquid, partially neutralized sulfate aerosol particles at 293 +/- 1 K and <5% relative humidity. Isoprene-derived epoxydiols (IEPOX) were taken up for all neutralizations so long as the liquid phase was maintained. By comparison, isoprene-derived hydroperoxides (ISOPOOH) were taken up only for low neutralization (i.e., high acidity). The release of product molecules to the gas phase increased for low neutralization, corresponding to the release of at least 60 product molecules for the uptake of 100 reactant molecules at the lowest neutralization. A major reaction pathway was hydroperoxide cleavage in the particle phase to produce volatile products. Product species larger than the C5 chain of isoprene were also released to the gas phase, implying that some accretion products in the particle phase were sufficiently volatile to partition to the gas phase. The study results show that the dependence of reactive uptake on neutralization varies by species. Furthermore, in addition to functionalization and accretion, decomposition and re-volatilization should be considered in mass balance formulations of reactive uptake by atmospheric particles. PMID- 26675581 TI - Intra-abdominal adhesions in ultrasound. Parts I and II. PMID- 26675582 TI - 25 years of N-heterocyclic carbenes: activation of both main-group element element bonds and NHCs themselves. AB - N-Heterocyclic carbenes (NHCs) are widely used ligands and reagents in modern inorganic synthesis as well as in homogeneous catalysis and organocatalysis. However, NHCs are not always innocent bystanders. In the last few years, more and more examples were reported of reactions of NHCs with main-group elements which resulted in modification of the NHC. Many of these reactions lead to ring expansion and the formation of six-membered heterocyclic rings involving insertion of the heteroatom into the C-N bond and migration of hydrides, phenyl groups or boron-containing fragments. Furthermore, a few related NHC rearrangements were observed some decades ago. In this Perspective, we summarise the history of NHC ring expansion reactions from the 1960s till the present. PMID- 26675583 TI - Standards of the Polish Ultrasound Society. Ultrasound examination of the portal system and hepatic vessels. AB - Increased incidence of liver diseases, the development of liver surgery and other invasive methods for managing portal hypertension, plus an increasing number of liver transplant procedures pose more and more new challenges for ultrasonography. Ultrasonography, being an effective and clinically verified modality, has been used for several decades for diagnosing diseases of the liver, its vessels and portal hypertension. It is used for both initial and specialist diagnosis (performed in reference centers). The diagnostic value of ultrasonography largely depends on the knowledge of anatomy, physiology, pathophysiology and clinical aspects as well as on the mastering of the scanning technique. In the hands of an experienced physician, it is an accurate and highly effective diagnostic tool; it is of little use otherwise. The paper presents elements of anatomy, physiology and pathophysiology which make the portal system exceptional and the knowledge of which is crucial and indispensable for a correct examination and, above all, for the correct interpretation of results. The authors also present requirements regarding the equipment. Moreover, various technical aspects of the examination are presented and the normal morphological picture and hemodynamic parameters of healthy individuals are described. The authors discuss the most common clinical situations and rare cases during ultrasound examinations. The paper is based on the experience of the author who works in the largest center of liver diseases in Poland, and on the current literature. PMID- 26675584 TI - Social density processes regulate the functioning and performance of foraging human teams. AB - Social density processes impact the activity and order of collective behaviours in a variety of biological systems. Much effort has been devoted to understanding how density of people affects collective human motion in the context of pedestrian flows. However, there is a distinct lack of empirical data investigating the effects of social density on human behaviour in cooperative contexts. Here, we examine the functioning and performance of human teams in a central-place foraging arena using high-resolution GPS data. We show that team functioning (level of coordination) is greatest at intermediate social densities, but contrary to our expectations, increased coordination at intermediate densities did not translate into improved collective foraging performance, and foraging accuracy was equivalent across our density treatments. We suggest that this is likely a consequence of foragers relying upon visual channels (local information) to achieve coordination but relying upon auditory channels (global information) to maximise foraging returns. These findings provide new insights for the development of more sophisticated models of human collective behaviour that consider different networks for communication (e.g. visual and vocal) that have the potential to operate simultaneously in cooperative contexts. PMID- 26675585 TI - Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non diabetic patients. AB - BACKGROUND: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. METHODS: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. RESULTS: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. CONCLUSION: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype. PMID- 26675586 TI - Vancomycin-resistant Enterococcus faecium with vanA gene isolated for the first time from wildlife in Slovakia. AB - Corvids have been identified as an important vector of vancomycin-resistant enterococci (VRE) in several European countries. The aim of this study was to assess the prevalence of VRE in wildlife in Slovakia and to characterize vanA carrying VRE. At the beginning of 2013, we collected 287 fecal samples of common raven (Corvus corax) in Petrovce and 99 fecal samples of rooks (Corvus frugilegus) in Kosice. Samples were cultured selectively on Slanetz-Bartley agar with vancomycin and screened for vanA, other resistance genes, and virulence genes. PCR mapping of Tn1546 carrying vanA gene was performed. Multilocus sequence typing and pulsed-field gel electrophoresis were used to examine the genotypic diversity of vanA-containing VRE. The mobility of vancomycin resistance traits was tested in vitro, using filter mating experiments. VRE with the vanA gene were found in 4 (1.4%) of 287 raven samples and in one (1%) of 99 rook samples. All 5 isolates belonged to Enterococcus faecium and were multiresistant with resistance to erythromycin encoded by the erm(B) gene, tetracycline (tet(M) and tet(L) genes), and ampicillin (mutations in C-terminal region of pbp5 gene). Isolates from Petrovce also were resistant to chloramphenicol. Virulence genes were not proven. The vanA gene was carried by Tn1546 types E (combined with insertion sequence IS1216) or F5 (IS1251). One isolate from a rook in Kosice belonged to ST (sequence type) 6 and the remaining four from ravens in Petrovce belonged to new ST917 (a single locus variant of ST18). All tested VRE were able to transfer the vancomycin resistance trait. In conclusion, we identified clinically important enterococci with the vanA gene in corvids in Slovakia. PMID- 26675587 TI - Assessing the pollution risk of soil Chromium based on loading capacity of paddy soil at a regional scale. AB - The accumulation of a trace metal in rice grain is not only affected by the total concentration of the soil trace metal, but also by crop variety and related soil properties, such as soil pH, soil organic matter (SOM) and so on. However, these factors were seldom considered in previous studies on mapping the pollution risk of trace metals in paddy soil at a regional scale. In this study, the spatial nonstationary relationships between rice-Cr and a set of perceived soil properties (soil-Cr, soil pH and SOM) were explored using geographically weighted regression; and the relationships were then used for calculating the critical threshold (CT) of soil-Cr concentration that may ensure the concentration of rice Cr being below the permissible limit. The concept of "loading capacity" (LC) for Cr in paddy soil was then defined as the difference between the CT and the real concentration of Cr in paddy soil, so as to map the pollution risk of soil-Cr to rice grain and assess the risk areas in Jiaxing city, China. Compared with the information of the concentration of the total soil-Cr, such results are more valuable for spatial decision making in reducing the accumulation of rice-Cr at a regional scale. PMID- 26675589 TI - Introduction: December 2015 HeartWeek Issue of Cardiology in the Young - Highlights of HeartWeek 2015: Challenges and Dilemmas of Pediatric Cardiac Care including Heart Failure in Children and Congenital Abnormalities of the Coronary Arteries. AB - This December Issue of Cardiology in the Young represents the 13th annual publication in Cardiology in the Young generated from the two meetings that composed "HeartWeek in Florida". "HeartWeek in Florida", the joint collaborative project sponsored by the Cardiac Centre at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, together with Johns Hopkins All Children's Heart Institute of Saint Petersburg, Florida, averages over 1000 attendees every year and is now recognised as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the foetus, neonate, infant, child, and adult. "HeartWeek in Florida" combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine, and entering its 16th year, with the Annual Postgraduate Course in Paediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia entering its 19th year. This December 2015 Issue of Cardiology in the Young features highlights of the two meetings that compose HeartWeek. Johns Hopkins All Children's Heart Institute's 15th Annual International Symposium on Congenital Heart Disease was held at the Renaissance Vinoy Resort & Golf Club, Saint Petersburg, Florida, from Friday, 6 February, 2015, to Monday, 9 February, 2015. This Symposium was co-sponsored by The American Association for Thoracic Surgery and its special focus was "Congenital Abnormalities of the Coronary Arteries". The Children's Hospital of Philadelphia's annual meeting - Cardiology 2015, the 18th Annual Update on Paediatric and Congenital Cardiovascular Disease: "Challenges and Dilemmas" - was held at the Hyatt Regency Scottsdale Resort and Spa at Gainey Ranch, Scottsdale, Arizona, from Wednesday, 11 February, 2015, to Sunday, 15 February, 2015. We would like to acknowledge the tremendous contributions made to paediatric and congenital cardiac care by Juan Valentin Comas, MD, PhD (13 May, 1960 to 16 June, 2015) and Donald Nixon Ross, FRCS (4 October, 1922 to 7 July, 2014); and therefore, we dedicate this December 2015 HeartWeek Issue of Cardiology in the Young to them. PMID- 26675588 TI - Size Distribution of Sperm Whales Acoustically Identified during Long Term Deep Sea Monitoring in the Ionian Sea. AB - The sperm whale (Physeter macrocephalus) emits a typical short acoustic signal, defined as a "click", almost continuously while diving. It is produced in different time patterns to acoustically explore the environment and communicate with conspecifics. Each emitted click has a multi-pulse structure, resulting from the production of the sound within the sperm whale's head. A Stable Inter Pulse Interval (Stable IPI) can be identified among the pulses that compose a single click. Applying specific algorithms, the measurement of this interval provides useful information to assess the total length of the animal recorded. In January 2005, a cabled hydrophone array was deployed at a depth of 2,100 m in the Central Mediterranean Sea, 25 km offshore Catania (Ionian Sea). The acoustic antenna, named OnuDE (Ocean noise Detection Experiment), was in operation until November 2006. OnuDE provided real time acoustic data used to perform Passive Acoustic Monitoring (PAM) of cetacean sound emissions. In this work, an innovative approach was applied to automatically measure the Stable IPI of the clicks, performing a cepstrum analysis to the energy (square amplitude) of the signals. About 2,100 five-minute recordings were processed to study the size distribution of the sperm whales detected during the OnuDE long term deep-sea acoustic monitoring. Stable IPIs were measured in the range between 2.1 ms and 6.4 ms. The equations of Gordon (1991) and of Growcott (2011) were used to convert the IPIs into measures of size. The results revealed that the sperm whales recorded were distributed in length from about 7.5 m to 14 m. The size category most represented was from 9 m to 12 m (adult females or juvenile males) and specimens longer than 14 m (old males) seemed to be absent. PMID- 26675590 TI - Lost treasures: a plea for the systematic preservation of cadaveric heart specimens through three-dimensional digital imaging. PMID- 26675591 TI - Epidemiology and cost of heart failure in children. AB - Heart failure in children is a complex disease process, which can occur secondary to a variety of aetiologies, including CHD, cardiomyopathy, or acquired conditions as well. Although the overall incidence of disease is low, the associated morbidity and mortality are high. Mortality may have decreased slightly over the last decade, and this is likely due to our ability to shepherd patients through longer periods of significant morbidity, with lasting effects. Costs of heart failure are significant - on the order of $1 billion annually as hospital charges for inpatient admissions alone. The value, or benefit to patient life and quality of life at this cost, is not well delineated. Further research is needed to optimise not only outcomes for these patients but also the high costs associated with them. PMID- 26675592 TI - Biomarkers in paediatric heart failure: is there value? AB - A biomarker is any measurable, surrogate characteristic, which reflects either the presence or the absence of a disease state. This can be a blood test, an imaging characteristic, an exercise parameter, and even a genetic profile. Serum biomarkers are particularly attractive in that their cost to the patient is relatively low in terms of money, time, risk, and ease of obtaining a sample. The potential benefits of a good biomarker are manifold. This manuscript will review serum biomarkers of proposed utility in paediatric heart failure, especially with respect to their ability to aid clinical decision making, diagnosis, and prognosis. PMID- 26675594 TI - Characterising adequacy or inadequacy of the borderline left ventricle: what tools can we use? AB - Borderline left ventricle refers to a spectrum of left ventricular underdevelopment, typically associated with other cardiac anomalies. The left ventricle may be mildly hypoplastic, as is sometimes seen accompanying aortic coarctation, or it can be severely hypoplastic, as is seen in hypoplastic left heart syndrome. For patients with a borderline left ventricle that is at either extreme, the treatment decision is relatively straightforward. Those with the most severe form of left ventricle hypoplasia will require single ventricle palliation or cardiac transplantation, whereas those with the mildest form may not need any intervention. It is the management strategy of children that fall within the grey zone of the spectrum, which continues to be controversial and remains variable within and among different institutions. Cardiac diseases with associated left ventricle hypoplasia include critical aortic stenosis, mitral stenosis, coarctation of the aorta, arch hypoplasia, cor triatriatum, unbalanced common atrioventricular canal, Shone's complex, total anomalous pulmonary venous return, and complex conotruncal abnormalities. In this review, we will discuss the assessment and management of infants with borderline left ventricle with critical aortic stenosis or arch obstruction and associated mitral anomalies. PMID- 26675595 TI - Pulmonary vasodilator therapy in the failing Fontan circulation: rationale and efficacy. AB - The Fontan operation is the final step of palliation for patients with a functionally single ventricle. Since its introduction in the 1970s, the Fontan surgery has become part of a successful surgical strategy that has improved single ventricle mortality. In recent years, we have become more aware of the limitations and long-term consequences of the Fontan physiology. Pulmonary vascular resistance plays an important role in total cavopulmonary circulation, and has been identified as a potential therapeutic target to mitigate Fontan sequelae. In this review, we will discuss the results of different pulmonary vasodilator trials and the use of pulmonary vasodilators as a treatment strategy for Fontan patients. PMID- 26675593 TI - How best to assess right ventricular function by echocardiography. AB - Right ventricular function is a crucial determinant of long-term outcomes of children with heart disease. Quantification of right ventricular systolic and diastolic performance by echocardiography is of paramount importance, given the prevalence of children with heart disease, particularly those with involvement of the right heart, such as single or systemic right ventricles, tetralogy of Fallot, and pulmonary arterial hypertension. Identification of poor right ventricular performance can provide an opportunity to intervene. In this review, we will go through the different systolic and diastolic indices, as well as their application in practice. Quantification of right ventricular function is possible and should be routinely performed using a combination of different measures, taking into account each disease state. Quantification is extremely useful for individual patient follow-up. Laboratories should continue to strive to optimise reproducibility through quality improvement and quality assurance efforts in addition to investing in technology and training for new, promising techniques, such as three-dimensional echocardiography. PMID- 26675596 TI - The anatomy and development of normal and abnormal coronary arteries. AB - At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death. PMID- 26675597 TI - Echocardiographic evaluation of coronary arteries in congenital heart disease. AB - Among populations of patients with the congenital heart disease, there is considerable diversity in the anatomy of the coronary arteries. Understanding these anatomical differences is vitally important in directing interventions and surgical repair. In this report, the authors describe the echocardiographic evaluation of the variants of coronary artery anatomy in the following lesions: transposition of the great arteries, congenitally corrected transposition of the great arteries, double-inlet left ventricle, common arterial trunk, tetralogy of Fallot, and double-outlet right ventricle. PMID- 26675598 TI - Echocardiographic presentation of anomalous origin of the left coronary artery from the pulmonary artery. AB - In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients. PMID- 26675599 TI - Stress echocardiography in paediatrics: implications for the evaluation of anomalous aortic origin of the coronary arteries. AB - Stress echocardiography in paediatrics is used to evaluate pre- and post operative coronary artery conditions, as well as to gain haemodynamic information for a variety of diagnoses, although evidence regarding sensitivity, specificity, and predictive value is lacking. This review will consider the available literature with a focus on anomalous aortic origin of the coronary arteries and discuss a practical approach to test selection and use. PMID- 26675600 TI - Near-fatal neonatal coronary ischaemia associated with intermittent aortic regurgitation: successful surgical treatment. AB - An infant presented with features suggestive of an anomalous left coronary artery was found to have normal origins of both coronary arteries. Echocardiography during episodes of ischaemia showed marked aortic regurgitation with retrograde coronary flow. The left coronary leaflet was mildly hypoplastic. Surgical re suspension of this leaflet prevented aortic regurgitation and the patient had no further symptoms and recovered cardiac function. PMID- 26675601 TI - Clinical examples of congenital abnormalities of the coronary arteries. PMID- 26675602 TI - Primary-care management of patients with congenital anomalies of the coronary arteries. AB - Congenital anomalies of the coronary arteries, although uncommon, have the potential to cause serious myocardial damage, ischaemic cardiomyopathy, and sudden cardiac death. This article summarises aspects of care for these patients in the outpatient setting, including clinical history and physical examination findings, ancillary testing, decision-making regarding the need for surgical intervention, and recommendations for physical activity. Although there are limited data regarding some of these recommendations, it is hoped that these can be used as an initial benchmark against which further data will lead to a more evidence-based approach. PMID- 26675603 TI - Repair techniques for anomalous aortic origins of the coronary arteries. AB - Anomalous aortic origins of the coronary arteries comprise approximately one third of all coronary artery anomalies and are characterised by coronary arteries with anomalies of aortic origin involving abnormal courses, stenoses, and compression that can lead to myocardial ischaemia and sudden death. Operative techniques to treat these anomalies have not been standardised yet. Moreover, the management of potential complications has not been addressed. Common and rare forms of anomalous aortic origins of the coronary arteries are reviewed and understood standard techniques for an uncomplicated unroofing procedure are illustrated. Also noted are techniques that can be applied to unexpected anatomical findings and unwanted complications that could prove to be life threatening. Several technical recommendations are offered. PMID- 26675604 TI - Critical care for patients with congenital abnormalities of the coronary arteries. AB - Congenital abnormalities of the coronary arteries in the absence of structural heart disease account for a small but interesting percentage of cardiac lesions in children. Their presentation may vary from incidental identification to aborted/sudden cardiac death. Patients with aborted sudden death episodes will require significant support if they develop extensive ischaemic myocardial injury. Ultimately, surgical repair should be carried out as soon as haemodynamic stability is attained and the neurological status is evaluated. The aims of this article were to provide a review of congenital abnormalities of the coronary arteries most commonly seen in children in the ICU as well as to review the current critical-care management thereof. PMID- 26675605 TI - The Congenital Heart Surgeons' Society Registry of Anomalous Aortic Origin of a Coronary Artery: an update. AB - The anomalous aortic origin of a coronary artery from the wrong sinus of Valsalva with an interarterial, intramural, and/or intraconal course is a relatively rare congenital defect of the heart that may be associated with an increased risk of ischaemia of the myocardium and sudden death, notably in children and young adults. Data are limited regarding stratification of risk and long-term outcomes of these patients. In 2009, the Anomalous Coronary Artery Working Group formed the Congenital Heart Surgeons' Society Registry of Anomalous Aortic Origin of a Coronary Artery to obtain information on large numbers of young patients with anomalous aortic origin of a coronary artery with the goal to better understand the natural and surgical history of this anomaly as well as to develop evidence based treatment and management guidelines. In this report, we describe the data we have collected from the registry and the current state of the registry. PMID- 26675606 TI - Higher programmatic volume in paediatric heart surgery is associated with better early outcomes. AB - OBJECTIVE: Previous analyses have suggested an association between centre volume and in-hospital mortality, post-operative complications, and mortality in those patients who suffer from a complication. We sought to determine the nature of this association using a multicentre cohort. METHODS: All the patients, aged 18 years or younger, undergoing heart surgery at centres participating in the European Congenital Heart Surgeons Database (2003-2013) were included. Programmes were grouped as follows: small 350. Multivariable logistic regression was used to identify the differences between groups with the adjusted in-hospital mortality, onset of any and/or major complication, and in-hospital mortality in those patients with any and/or major complication. The outcomes were adjusted for patient specific risk factors and surgical risk factors. RESULTS: The data set consisted of 119,345 procedures performed in 99 centres. Overall, in-hospital mortality was 4.63%; complications occurred in 23.4% of the patients. In-hospital mortality in patients with complications was 13.82%. Multivariable logistic regression showed that the risk of in-hospital death was higher in low- and medium-volume centres (p<0.001). The rate of the occurrence of any post-operative complication in small, medium, and large programmes was lower compared with very large centres (p<0.001). Low- and medium-volume centres were associated with significantly higher mortality in patients with any complication (p<0.001). CONCLUSIONS: Our analysis showed that the risk of in-hospital mortality was lower in higher-volume centres. Although the risk of complications is higher in high volume centres, the mortality associated with complications that occurred in these centres was lower. PMID- 26675607 TI - The development of a congenital heart programme quality dashboard to promote transparent reporting of outcomes. AB - In 2001, the Institute of Medicine identified healthcare transparency as a necessity for re-designing a quality healthcare system; however, despite widespread calls for publicly available transparent data, the goal remains elusive. The transparent reporting of outcome data and the results of congenital heart surgery is critical to inform patients and families who have both the wish and the ability to choose where care is provided. Indeed, in an era where data and means of communication of data have never been easier, the paucity of transparent data reporting is paradoxical. We describe the development of a quality dashboard used to inform staff, patients, and families about the outcomes of congenital heart surgery at the Stollery Children's Hospital. PMID- 26675608 TI - Social media in paediatric heart disease: professional use and opportunities to improve cardiac care. AB - Social media is any type of communication utilising electronic technology that follows two guiding principles: free publishing or sharing of content and ideas and group collaboration and inter-connectedness. Over the last 10 years, social media technology has made tremendous inroads into all facets of communication. Modalities such as Facebook, YouTube, and Twitter are no longer viewed as new communication technologies. Owing to their tremendous usage, they are now common ways to conduct a dialogue with individuals and groups. Greater than 91% of teenagers and 89% of young adults routinely use social media. Further, 24% of teenagers reported being online "almost constantly". These forms of communication are readily used by individuals cared for in the field of paediatric cardiology; thus, they should carry significant interest for cardiology care providers; however, social media's influence on medicine extends beyond use by patients. It directly affects all medical providers, both users and non-users. Further, social media has the ability to improve care for patients with paediatric heart disease. This article details social media's current influence on paediatric cardiology, including considerations for professional use of social media and potential opportunities to improve cardiac care. PMID- 26675609 TI - Surveillance of fetal arrhythmias in the outpatient setting: current limitations and call for action. AB - Surveillance of fetal arrhythmias in the outpatient setting remains limited by lack of monitoring modalities. Despite technological advances made in the field of obstetrics, existing devices are not currently suitable to monitor fetal arrhythmias. In this report, the author describes the current and developing fetal heart rate monitoring technologies including the recent introduction of hand-held Doppler monitors for outpatient surveillance of fetal arrhythmias. PMID- 26675611 TI - Commentary on the required skills for ambulatory cardiac care in the young: is training necessary? AB - Extensive supplemental training exists for many subspecialty disciplines within fellowship training for paediatric cardiology in the United States of America. These disciplines, or domains, such as echocardiography, cardiac intensive care, interventional cardiology, and electrophysiology, allow for initial exposure and training during the basic 3 years of fellowship, plus mandate a 4th year of advanced training; however, ambulatory cardiology has no in-depth or additional training beyond the basic clinical exposure during fellowship training. Ambulatory cardiology is not included in the recommended scheduling of the various domains of cardiology training. This document reviews the reasons to consider augmenting the depth and breadth of training in ambulatory paediatric cardiology. PMID- 26675612 TI - Pregnancy in complex CHD: focus on patients with Fontan circulation and patients with a systemic right ventricle. AB - The majority of children with congenital heart disease (CHD) now survive into adulthood, and many women with CHD want to pursue pregnancy. Pregnancy represents a complex issue for the CHD care provider. It requires balancing the interests of the woman against the risk to her health during pregnancy, while also factoring in the long-term risks to her health and the risk to her fetus. Our knowledge about this subject has been historically limited by lack of data regarding the outcome of pregnancy in CHD; however, in recent years, more data have begun to emerge. In this review, we will summarise what is known about risk assessment in pregnant CHD patients. We provide a framework for healthcare providers managing pregnancy in this population, with focus on the systemic right ventricle and the Fontan operation. PMID- 26675610 TI - Perioperative feeding management of neonates with CHD: analysis of the Pediatric Cardiac Critical Care Consortium (PC4) registry. AB - Introduction The optimal perioperative feeding strategies for neonates with CHD are unknown. In the present study, we describe the current feeding practices across a multi-institutional cohort. METHODS: Inclusion criteria for this study were as follows: all neonates undergoing cardiac surgery admitted to the cardiac ICU for ?24 hours preoperatively between October, 2013 and July, 2014 in the Pediatric Cardiac Critical Care Consortium registry. RESULTS: The cohort included 251 patients from eight centres. The most common diagnoses included the following: hypoplastic left heart syndrome (17%), coarctation/aortic arch hypoplasia (18%), and transposition of the great arteries (22%); 14% of the patients were <37weeks of gestational age. The median total hospital length of stay was 21 days (interquartile range (IQR) 14-35) and overall mortality was 8%. Preoperative feeding occurred in 133 (53%) patients. The overall preoperative feeding rates across centres ranged from 29 to 79%. Postoperative feeds started on median day 2 (IQR 1-4); for patients with hypoplastic left heart syndrome postoperative feeds started on median day 4. Postoperative feeds were initiated in 89 (35%) patients before extubation (range across centres: 21-61%). The median cardiac ICU discharge feeding volume was 108 cc/kg/day, varying across centres. The mean discharge weight was 280 g above birth weight, ranging from +100 to 430 g across centres. A total of 110 (44%) patients had discharge feeding tubes, ranging from 6 to 80% across centres, and 40/110 patients had gastrostomy/enterostomy tubes placed. In addition, eight (3.2%) patients developed necrotising enterocolitis - three preoperatively and five postoperatively. CONCLUSION: In this cohort, neonatal feeding practices and outcomes appear to vary across diagnostic groups and institutions. Only half of the patients received preoperative enteral nutrition; almost half had discharge feeding tubes. Multi-institutional collaboration is necessary to determine feeding strategies associated with best clinical outcomes. PMID- 26675613 TI - Respect for patient autonomy as a medical virtue. AB - Respect for patient autonomy is an important and indispensable principle in the ethical practice of clinical medicine. Legal tenets recognise the centrality of this principle and the inherent right of patients of sound mind - properly informed - to make their own personal medical decisions. In the course of everyday medical practice, however, challenging cases may result in ethical dilemmas for the patient, the physician, and society. Resolution of these dilemmas requires a thorough understanding of the underlying principles that allow the clinician to make informed decisions and to offer considered therapeutic options to the patient. We argue in this paper that there is also need for a transition of moral competency from understanding principles to attaining virtue in the classic Aristotelian tradition. Achieving moral virtue is based on a lifetime of learning, practising, and watching how others, who have achieved virtue, act and perform their duties. We further claim that learning moral virtue in medical practice is best realised by incorporating the lessons learnt during daily rounds where frank discussions and considered resolutions can occur under the leadership of senior practitioners who have achieved a semblance of moral excellence. PMID- 26675614 TI - The elephant in the room: ethical issues associated with rare and expensive medical conditions. AB - The treatment of rare and expensive medical conditions is one of the defining qualities of paediatric cardiology and congenital heart surgery. Increasing concerns over healthcare resource allocation are challenging the merits of treating more expensive forms of congenital heart disease, and this trend will almost certainly continue. In this manuscript, the problems of resource allocation for rare and expensive medical conditions are described from philosophical and economic perspectives. The argument is made that current economic models are limited in the ability to assess the value of treating expensive and rare forms of congenital heart disease. Further, multi-disciplinary approaches are necessary to best determine the merits of treating a patient population such as those with significant congenital heart disease that sometimes requires enormous healthcare resources. PMID- 26675615 TI - The MAVID heart holder: a demonstration device to anchor cadaver hearts for surgical simulation and practical education. AB - Performing open heart surgery involves learning challenging techniques and a need for realistic training models to achieve and maintain a high level of surgical skills. The MAVID heart holder is an organ holder primarily designed to hold the heart in its anatomic position for the purpose of surgical simulation and education, thereby closing the gap between surgical performance in the laboratory and in the operating room. The device is simple to use, can be adjusted to organ size, and has the necessary instrumentation to be used with any solid organ. The MAVID heart holder also provides a platform for presentation and assists in advancing the research sphere. The advantage over other existing models is that the MAVID heart holder uses real tissue and does not distort the organ at the attachment sites. Further, it offers superior stability as well as the ability to manipulate the organ during presentation and dissection. Training with the MAVID heart holder has the potential to shorten training time to acquire surgical skills and proficiency before performing these techniques in the operating room and in so doing enhance patient safety. PMID- 26675616 TI - Overview of left ventricular outpouchings on cardiac magnetic resonance imaging. AB - Left ventricular outpouchings commonly include aneurysm, pseudoaneurysm, and diverticulum and are now being increasingly detected on imaging. Distinction between these entities is of prime importance to guide proper management as outcomes for these entities differ substantially. Chest radiograph is usually nonspecific in their diagnosis. Echocardiography, multi-detector computed tomography evaluation and angiography are helpful in the diagnosis with their inherit limitations. Cardiac magnetic resonance imaging (MRI) is emerging as a very useful tool that allows simultaneous anatomical and functional evaluation along with tissue characterization, which has diagnostic, theraputic and prognostic implications. This article gives an overview of left ventricular outpouchings with special emphasis on their differentiation using cardiac MRI. PMID- 26664705 TI - Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus. AB - Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus ( p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus ( p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated nocturnal dipping and nocturnal hypertension in SLE patients. PMID- 26675620 TI - Synthesis and Characterization of [n]CPP (n = 5, 6, 8, 10, and 12) Radical Cation and Dications: Size-Dependent Absorption, Spin, and Charge Delocalization. AB - Radical cations and dications of [n]cyclo-p-phenylenes ([n]CPPs, n = 5, 6, 10, and 12), which are the models of those of linear oligo-p-phenylenes without a terminus, were synthesized as hexafluoroantimonate salts by the one- and two electron chemical oxidation of CPP by NOSbF6 or SbF5. The radical cations, [n]CPP(*+), and dications, [n]CPP(2+), exhibited remarkable bathochromic shifts in their UV-vis-NIR absorption bands, suggesting that [n]CPP(*+) and larger [n]CPP(2+) exhibit longer polyene character than the shorter analogues. The larger bathochromic shift was consistent with the narrower HOMO-SOMO and HOMO LUMO gaps in larger [n]CPP(*+) and [n]CPP(2+), respectively. In [n]CPP(*+), the spins and charges were equally and fully delocalized over the p-phenylene rings of the CPPs, as noted by ESR. (1)H NMR revealed that the hydrogen of [n]CPP(2+) shifted to a high magnetic field from the neutral compounds due to the diamagnetic ring current derived from the in-plane aromaticity of [n]CPP(2+). The single resonances observed in all [n]CPP(2+) strongly suggest the complete delocalization of the charges over the CPPs. Furthermore, the contribution of biradical character was clarified for [10]- and [12]CPP by VT-NMR experiment and theoretical calculation. PMID- 26675618 TI - GTPase Activating Protein (Sh3 Domain) Binding Protein 1 Regulates the Processing of MicroRNA-1 during Cardiac Hypertrophy. AB - BACKGROUND: MicroRNAs (miR) are small, posttranscriptional regulators, expressed as part of a longer primary transcript, following which they undergo nuclear and cytoplasmic processing by Drosha and Dicer, respectively, to form the functional mature ~20mer that gets incorporated into the silencing complex. Others and we have shown that mature miR-1 levels decrease with pressure-induced cardiac hypertrophy, however, there is little or no change in the primary transcript encompassing miR-1 stem-loop, suggesting critical regulatory step in microRNA processing. The objective of this study was to investigate the underlying mechanisms regulating miR-1 expression in cardiomyocytes. RESULTS: Here we report that GTPase-activating protein (SH3 domain) binding protein 1 (G3bp1), an endoribonuclease regulates miR-1 processing in cardiomyocytes. G3bp1 is upregulated during cardiac hypertrophy and restricts miR-1 processing by binding to its consensus sequence in the pre-miR-1-2 stem-loop. In accordance, exogenous G3bp1 is sufficient to reduce miR-1 levels, along with derepression of miR-1 targets; General transcription factor IIB (Gtf2b), cyclin dependent factor 9 (Cdk9) and eukaryotic initiation factor 4E (Eif4e). While Cdk9 and Gtf2b are essential for transcription, Eif4e is required for translation. Thus, downregulation of miR-1 is necessary for increase in these molecules. Similar to miR-1 knockdown, G3bp1 overexpression is not sufficient for development of cardiac hypertrophy. Conversely, knockdown of G3bp1 in hypertrophying cardiomyocytes inhibited downregulation of miR-1 and upregulation of its targets along with restricted hypertrophy, suggesting that G3bp1 is necessary for development of cardiac hypertrophy. These results indicate that G3bp1-mediated inhibition of miR-1 processing with growth stimulation results in decrease in mature miR-1 and, thereby, an increase of its targets, which play fundamental roles in the development of hypertrophy. CONCLUSION: G3bp1 posttranscriptionally regulates miRNA-1 processing in the heart, and G3bp1 mediated downregulation of mature miRNA-1 levels is required for the derepression of its targets and increase in gene expression during cardiac hypertrophy. PMID- 26675619 TI - The prevalence and impact of antimicrobial allergies and adverse drug reactions at an Australian tertiary centre. AB - BACKGROUND: The prevalence and impact of antimicrobial "allergy" labels and Adverse Drug Reactions (ADRs) on antibiotic usage and antimicrobial stewardship initiatives is ill defined. We sought to examine the rate of antimicrobial "allergy labels" at our tertiary referral centre and impacts on antimicrobial usage and appropriateness. METHODS: Two inpatient antimicrobial prevalence surveys were conducted over a 1-week period in November 2013 and 2014 as part of the prospective National Antimicrobial Prescribing Survey (NAPS). Post survey, patients recorded in the NAPS database were assigned to two groups based upon recorded antimicrobial "allergy label" and ADR: (i) Antimicrobial Allergy/ADR (AA) or (ii) No Antimicrobial Allergy/ADR (NAA). Antimicrobial usage and antimicrobial appropriateness were compared between AA and NAA groups. RESULTS: From 509 identified patients the prevalence of an antimicrobial allergy or ADR was 25 %. The prevalence of "allergy labels"/ADR was 10 % (51/509) for penicillin V/G, 5 % (24/509) cephalosporins, 4 % (22/509) trimethroprim-sulfamethoxazole and 3 % (17/509) aminopenicillins. One thousand and seventy antimicrobials were prescribed during the study periods, the median antimicrobial duration was longer in the AA versus NAA group (6 days vs. 4 days; p = 0.018), and proportion of inappropriate antimicrobial prescribing higher in the AA group compared with NAA (29 %; 35/120 vs. 23 %; 86/367, p = 0.22). Oral antimicrobial administration was higher in the NAA than AA group (60 %; 177/297 vs. 46 %; 356/793, p = 0.0001). The proportion of patients that received a beta-lactam was lower in the AA versus NAA group (60 % vs. 79 %, p = 0.0001). CONCLUSIONS: In an Australian tertiary referral centre an antimicrobial "allergy" or ADR label was found to significantly impacted on rate of oral antimicrobial administration, beta-lactam usage, antimicrobial duration and antimicrobial appropriateness. PMID- 26675621 TI - Spontaneous Trans-Abdominal Expulsion of a Foreign Body: A Rare Occurrence. AB - Large and sharp foreign bodies invariably need surgical removal. A 55-year-old male, had epigastric pain, two weeks after accidental ingestion of wooden tooth brush. Later he developed pain, fever and indurations in left iliac fossa followed by spontaneous expulsion of foreign body through indurated area on the anterior abdominal wall. Contrast enhanced computed tomography revealed an inflammatory tract along the posterior wall of stomach communicating with the anterior abdominal wall. Patient was managed conservatively and made an uneventful recovery. PMID- 26675622 TI - Is a wake-up call in order? Review of the evidence for awake craniotomy. AB - Awake craniotomy (AC) has been used in increasing frequency in the past few decades. It has mainly been used for resection of intrinsic tumors, but also, rarely, for other pathologies. The vast majority of reports specific to one pathology, however, have focused on resection of low grade glioma in the awake setting. Tumors in eloquent areas have mainly been resected when the patient is awake for the purpose of preservation of function. Motor function is the most documented, and most successfully preserved function. Other functions are harder to localize with direct electrical stimulation (DES), and thus more difficult to preserve. The success rate of DES localization correlates to the rate of function preservation. The effect of AC on extent of resection is inconsistent in the literature. Other functions, such as sensory and visuospatial recognition, have been protected during AC, but this is best performed in large, referral centers that have experience with the procedure. Other benefits to AC, such as cost effectiveness and reduction in patient pain and anxiety, have also been reported. PMID- 26675623 TI - Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis. AB - We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit. PMID- 26675624 TI - Choroid plexus of the fourth ventricle: Review and anatomic study highlighting anatomical variations. AB - Relatively few studies have been performed that analyze the morphology of the choroid plexus of the fourth ventricle. Due to the importance of this tissue as a landmark on imaging and during surgical intervention of the fourth ventricle, the authors performed a cadaveric study to better characterize this important structure. The choroid plexus of the fourth ventricle of 60 formalin fixed adult human brains was examined and measured. The horizontal distance from the midline to the lateral most point of the protruding tip of the horizontal limbs was measured. In the majority of the 60 brain specimens, right and left horizontal limbs of the choroid plexus were seen extending from the midline and protruding out of their respective lateral apertures of the fourth ventricle and into the subarachnoid space. However, on 3.3% of sides, there was absence of an extension into the foramen of Luschka and in one specimen, this lack of extension into the foramen of Luschka was bilateral. On two sides, there was discontinuity between the midline choroid plexus and the tuft of choroid just outside the foramen of Luschka. For specimens in which the choroid plexus did protrude through the foramen of Luschka (96.7%), these tufts were located anterior to the flocculus and inferolateral to the facial/vestibulocochlear nerve complex and posterosuperior to the glossopharyngeal/vagal/accessory complex. A thorough understanding of the normal and variant anatomy of the fourth ventricular choroid plexus is necessary for those who operate in, or interpret imaging of, this region. PMID- 26675625 TI - Post-hemorrhagic hydrocephalus presenting as cauda equina syndrome in a patient with spinal dysraphism. AB - Hydrocephalus has varied presentations in patients with a history of spinal dysraphism. This is a unique case of post-subarachnoid hemorrhage hydrocephalus presenting as cauda equina syndrome. We report on a 32-year-old woman with remotely repaired spinal defect who experienced subarachnoid hemorrhage and underwent anterior communicating artery aneurysm clipping. Post-operatively, she developed urinary and fecal incontinence as the sole presenting symptom of communicating post-hemorrhagic hydrocephalus. New neurological deficits in this population can also be attributed to recurrent cord tethering or syrinx, both of which were demonstrated on her lumbar spine MRI, but her incontinence resolved with external ventricular drain placement and cerebrospinal fluid diversion. There are few case reports of patients with closed neural tube defects and hydrocephalus and none in the adult population to our knowledge. Neurological change in patients with any history of spinal dysraphism may reflect altered cerebrospinal fluid dynamics affecting either end of the neuraxis. PMID- 26675626 TI - Zero-Inflated Beta Regression for Differential Abundance Analysis with Metagenomics Data. AB - Metagenomics data have been growing rapidly due to the advances in NGS technologies. One goal of human microbial studies is to detect abundance differences across clinical conditions. Besides small sample size and high dimension, metagenomics data are usually represented as compositions (proportions) with a large number of zeros and skewed distribution. Efficient tools for handling such compositional data need to be developed. We propose a zero-inflated beta regression approach (ZIBSeq) for identifying differentially abundant features between multiple clinical conditions. The proposed method takes the sparse nature of metagenomics data into account and handle the compositional data efficiently. Compared with other available methods, the proposed approach demonstrates better performance with large AUC values for most simulation studies. When applied to a human metagenomics data, it also identifies biologically important taxa reported from previous studies. The software in R is available upon request from the first author. PMID- 26675627 TI - Waking EEG signs of non-restoring sleep in primary insomnia patients. AB - OBJECTIVE: Subjective feelings of insufficient and non-restorative sleep are core symptoms of primary insomnia. Sleep has a restorative effect on next-day waking EEG activity, whereas sleep loss has non-restorative effects in good sleepers. We proposed to explore waking EEG activity in primary insomniacs the evening before, and the morning after, a night of sleep, in order to detect signs of morning hyper-arousal and non-restoring sleep that might explain the subjective feelings despite the absence of objective signs in polysomnography. METHOD: Pre-sleep (10 pm) and post-sleep (10 am) waking EEG activity was analyzed in 10 non-medicated primary insomniacs and matched control subjects. Beta and Gamma absolute power and EEG temporal coupling were obtained. Participants also evaluated subjective sleep quantity and quality. RESULTS: Insomnia patients evaluated their sleep as non-restorative and insufficient. Compared to pre-sleep, during post-sleep control subjects exhibited significantly decreased Beta and Gamma power and reduced synchronization among anterior and posterior regions, consistent with restoring effects of sleep. Insomnia patients showed no beneficial effects of sleep on these EEG parameters. CONCLUSION: Insomniacs are hyper-aroused during morning wakefulness and they do not benefit from preceding sleep. SIGNIFICANCE: Our study adds new knowledge to our understanding of the physiopathology of insomnia. PMID- 26675628 TI - Oscillatory decoupling differentiates auditory encoding deficits in children with listening problems. AB - OBJECTIVE: We sought to examine whether oscillatory EEG responses to a speech stimulus in both quiet and noise were different in children with listening problems than in children with normal hearing. METHODS: We employed a high resolution spectral-temporal analysis of the cortical auditory evoked potential in response to a 150 ms speech sound /da/ in quiet and 3 dB SNR in 21 typically developing children (mean age=10.7 years, standard deviation=1.7) and 44 children with reported listening problems (LP) with absence of hearing loss (mean age=10.3 years, standard deviation=1.6). Children with LP were assessed for auditory processing disorder (APD) by which 24 children had APD, and 20 children did not. Peak latencies, magnitudes, and frequencies were compared between these groups. RESULTS: Children with LP had frequency shifts in the theta, and alpha bands (p<0.05), and children with LP+APD had additional frequency (p<0.01) and latency shifts (p<0.05) in the upper beta and in the lower gamma bands. CONCLUSIONS: These results provide evidence for differences in higher level modulatory processing in children with LP, and that APD is driven by differences in early auditory encoding. SIGNIFICANCE: These findings may better guide future research toward improving the differential diagnosis and treatment of listening problems in this population of children. PMID- 26675629 TI - Serodiagnosis of Scrub Typhus at a Tertiary Care Hospital from Southern India. AB - INTRODUCTION: Scrub typhus, a zoonotic disease is one of the most covert emerging and re-emerging Rickettsial infections. There is an upsurge in the incidence of the disease worldwide with ever-changing habitat. Clinical diagnosis of scrub typhus is challenging as the signs and symptoms of scrub typhus are similar to other febrile illnesses. In developing countries, among the various laboratory tests to diagnose scrub typhus, Weil-Felix test is commonly performed despite its low sensitivity. The Immunofluorescence antibody (IFA) test has its limitations in terms of cost and expertise required. The present study was conducted to determine the seropositivity of IgM ELISA for scrub typhus in clinically suspected cases. MATERIALS AND METHODS: Weil-Felix test and IgM ELISA were performed using clinically suspected cases of scrub typhus using commercially available kits. RESULTS: Out of 482 samples tested, 109 were positive by both Weil-Felix test and IgM ELISA. One hundred and sixteen samples which were negative by Weil-Felix test reacted positive by IgM ELISA. Fourteen samples which were positive by Weil-Felix test were negative by ELISA. CONCLUSION: Owing to the limitations of the Weil-Felix test and IFA, commercially available recombinant IgM ELISA which has a good sensitivity and specificity may be an alternative in laboratories with moderate set up. PMID- 26675630 TI - Comparison of Outcomes of Intertrochanteric Fracture Fixation Using Percutaneous Compression Plate Between Stable and Unstable Fractures in the Elderly. AB - OBJECTIVES: To evaluate the outcomes of treatment with a percutaneous compression plate (PCCP) in stable and unstable intertrochanteric hip fractures. DESIGN: Clinical prospective nonrandomized cohort study. SETTING: San Cecilio University Hospital, Granada (Spain). A tertiary-care hospital. PATIENTS: Patients older than 65 years undergoing surgery for an intertrochanteric hip fracture (n = 657) were divided according to the OTA/AO classification, into stable (31-A1) (group A, n = 363) and unstable fractures (31-A2) (group B, n = 294). INTERVENTION: Osteosynthesis with a PCCP (Orthofix Inc). MAIN OUTCOME MEASUREMENTS: Blood loss, wound complications, postoperative pain, operative and fluoroscopy time, functional outcomes, device-related complications, consolidation time, and mortality. RESULTS: Patients with unstable fractures were significantly worse with respect to postoperative pain, immediately (P = 0.020), at 6 weeks (P = 0.0001), and at 3 months (P = 0.009), and with respect to independent walking ability at 6 weeks. No other significant differences were observed. CONCLUSIONS: The outcomes of osteosynthesis with PCCP seem to be equally satisfactory in stable and unstable intertrochanteric fractures, with stable fractures having less pain and a greater ability to walk earlier. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26675640 TI - Structural Transition of Cinnamate-Based Light-Responsive Ionic Liquids in Aqueous Solutions and Their Light-Tunable Rheological Properties. AB - Light-responsive wormlike micelles have important applications in fields such as microfluids, photoswichable fluids, and rheology control. However, single component light-responsive wormlike micelles formed only from a single tail surfactant have not been reported in literature. In this work, self-assembly behavior of 1-alkyl-3-methylimidazolium trans-ortho-methoxycinnamate [Cnmim][OMCA] (n = 8, 10, 12, 14, 16) ionic liquids in aqueous solutions is studied by UV-vis spectroscopy, viscosity, rheology, conductivity, and cryo-TEM measurements. It is found for the first time that, among the single tail ionic liquid surfactants studied, [C16mim][OMCA] can form wormlike micelles in aqueous solutions without any additives and light irradiation. Then these wormlike micelles are able to transform into cylindrical micelles under UV light irradiation, resulting in significantly tunable rheological properties of the solutions. The photoisomerization of anion of [C16mim][OMCA] from trans- to cis isomer as well as the relative hydrophilicity and structural feature of the cis isomer are suggested to be responsible for such transition. PMID- 26675641 TI - Neurogenetics: Restoring levels. PMID- 26675642 TI - A new chiral Fe(III)-salen grafted mesoporous catalyst for enantioselective asymmetric ring opening of racemic epoxides at room temperature under solvent free conditions. AB - We have designed a new mesoporous SBA-15 supported chiral Fe(III)-salen material (Fe@SBSAL) having high BET surface area and porosity. The material showed excellent catalytic efficiency in regio- and enantioselective (ee > 99%) asymmetric ring opening (ARO) of racemic meso- and terminal-epoxides with various anilines at room temperature under solvent-free conditions within 1-3 h reaction time. PMID- 26675643 TI - Patient perspectives on an opioid overdose education and naloxone distribution program in the U.S. Department of Veterans Affairs. AB - BACKGROUND: In an effort to prevent opioid overdose mortality among Veterans, Department of Veterans Affairs (VA) facilities began implementing opioid overdose education and naloxone distribution (OEND) in 2013 and a national program began in 2014. VA is the first national health care system to implement OEND. The goal of this study is to examine patient perceptions of OEND training and naloxone kits. METHODS: Four focus groups were conducted between December 2014 and February 2015 with 21 patients trained in OEND. Participants were recruited from a VA residential facility in California with a substance use disorder treatment program (mandatory OEND training) and a homeless program (optional OEND training). Data were analyzed using matrices and open and closed coding approaches to identify participants' perspectives on OEND training including benefits, concerns, differing opinions, and suggestions for improvement. RESULTS: Veterans thought OEND training was interesting, novel, and empowering, and that naloxone kits will save lives. Some veterans expressed concern about using syringes in the kits. A few patients who never used opioids were not interested in receiving kits. Veterans had differing opinions about legal and liability issues, whether naloxone kits might contribute to relapse, and whether and how to involve family in training. Some veterans expressed uncertainty about the effects of naloxone. Suggested improvements included active learning approaches, enhanced training materials, and increased advertisement. CONCLUSIONS: OEND training was generally well received among study participants, including those with no indication for a naloxone kit. Patients described a need for OEND and believed it could save lives. Patient feedback on OEND training benefits, concerns, opinions, and suggestions provides important insights to inform future OEND training programs both within VA and in other health care settings. Training is critical to maximizing the potential for OEND to save lives, and this study includes specific suggestions for improving the effectiveness and acceptability of training. PMID- 26675644 TI - Analysis of Multidomain Protein Dynamics. AB - Proteins with a modular architecture of multiple domains connected by linkers often exhibit diversity in the relative positions of domains, while the domain tertiary structure remains unchanged. The biological function of these modular proteins, or the regulation of their activity, depends on the variation in domain orientation and separation. Accordingly, careful characterization of interdomain motion and correlated fluctuations of multidomain systems is relevant for understanding the functional behavior of modular proteins. Molecular dynamics (MD) simulations provides a powerful approach to study these motions in atomic detail. Nevertheless, the common procedure for analyzing fluctuations from MD simulations after rigid-body alignment fails for multidomain proteins; it greatly overestimates correlated positional fluctuations in the presence of relative domain motion. We show here that expressing the atomic motions of a multidomain protein as a combination of displacement within the domain reference frame and motion of the relative domains correctly separates the internal motions to allow a useful description of correlated fluctuations. We illustrate the methodology of separating the domain fluctuations and local fluctuations by application to the tandem SH2 domains of human Syk protein kinase and by characterizing an effect of phosphorylation on the dynamics. Correlated motions are assessed from a distance covariance rather than the more common vector-coordinate covariance. The approach makes it possible to calculate the proper correlations in fluctuations internal to a domain as well as between domains. PMID- 26675646 TI - [Diagnostics and treatment of calf vein thrombosis]. AB - Calf vein thrombosis is a much-debated entity. The literature shows that progression to deep venous thrombosis or pulmonary embolism occurs infrequently and is usually detected using serial two-point ultrasonography. Additionally, undetected and untreated calf vein thrombosis is not associated with serious adverse events in large management trials studying diagnostic strategies for suspected deep venous thrombosis. Recurrent venous thromboembolism can occur after calf vein thrombosis, but anticoagulant treatment does not reduce the incidence. In this article, three case histories describe the anatomical considerations for proper diagnosis of calf vein thrombosis, some aspects of the natural course, and the treatment that these patients received. A case is made for restrictive use of prolonged anticoagulation therapy as a means to reduce thromboembolic complications. Because symptomatic treatment has not been studied, expert opinion suggests a short (3-week) course of therapeutically-dosed low molecular-weight heparin. PMID- 26675645 TI - Alterations of the Neuroinflammatory Markers IL-6 and TRAIL in Alzheimer's Disease. AB - OBJECTIVE: We aimed to identify biomarkers of Alzheimer's disease (AD) in order to improve diagnostic accuracy at mild stage. METHODS: AD patients aged >50 years were included in the disease group. We evaluated the relationship between potential blood and cerebrospinal fluid inflammatory biomarkers, cognitive status, temporal lobe atrophy and disease severity. Inflammatory biomarkers including interleukin 6 (IL-6), IL-18, fractalkine and tumor necrosis factor related apoptosis-inducing ligand (TRAIL) levels were measured. APOE genotypes were determined. RESULTS: We enrolled 41 subjects in the disease group and 40 subjects in the normal control group. The majority (88.9%) of subjects in the disease group had mild AD. Elevated levels of plasma IL-6 and decreased levels of plasma TRAIL in the disease group were noted. Plasma levels of IL-6 and TRAIL were significantly correlated with their cerebrospinal fluid levels. CONCLUSION: Plasma IL-6 and TRAIL were identified as potential biomarkers of AD at an early stage. PMID- 26675647 TI - [What is the correct time to take medication?]. AB - In our professional lives as a hospital pharmacist/clinical pharmacologist and an internist/vascular medicine specialist, "time" plays an important role. Dosage recommendations are made based on elimination half-life and determination of drug levels is generally only useful after the patient has achieved the steady-state phase. Time effects also play a pharmacodynamic role. Some drugs work better when taken at bedtime than in the morning, certain cardiovascular drugs for example. We present an anthology of our activities over an average working day at Radboud University Medical Center, the Netherlands, whereby time plays an essential role. PMID- 26675648 TI - [The time of our lives]. AB - Prior to the industrial revolution in the mid-1800 s, the modal lifespan for humans was somewhat less than 75 years. Natural life expectancy was approximately 35 years, with a high child mortality rate strongly contributing to this low figure. At that time, natural life expectancy of someone aged 75 was 6 years, whereas the current life expectancy of, for example, a 75-year-old French woman is 14.5 years. The sharp increase in longevity means an added eight years of life in old age. Nevertheless, the rate of ageing, i.e. the degree of mortality-risk increase related to age, remains astonishingly constant. Preventive strategies that use the absolute risk of age-related diseases for setting treatment goals, in fact treat increasing age. For each population, the risk reaches its peak at a certain age; over a lifetime, the risk of death is always 100%. Under pressure from modern society and medicine, old age is now treated as a disease and medicalised to a great degree. To improve medical management of elderly patients, we will have to accustom ourselves to consider the goals of these actions, to ask ourselves: what is called wisdom? PMID- 26675649 TI - [Time to sleep; disruption of the biological clock due to night and shift work]. AB - Now that the 24-hour economy is putting an ever-increasing mark on social life, the effects of the disruption of natural biological rhythms are becoming clearer. In addition to its effects on sleep, this article discusses its long-term health effects. Potential measures to reduce and counteract the adverse effects of working night shifts on general well-being, sleep and health are summarized; the roles of light and rhythm are explored. Further research into the health effects of working nights and unsociable shift patterns is indicated. PMID- 26675650 TI - [Tailored pension age]. AB - Socio-economic inequalities in health have important consequences for employment and pensions. Less well educated people are often more unhealthy than those with a higher level of education. As a consequence, they are more likely to lose their jobs, and this in turn has negative effects on their health. Less well educated people lose more than 2 years of working life due to problems with their health; among those with higher level of education this loss is approximately 0.4 years. The influence of retirement on health shows some interesting differences; lower educated people seem to experience better health after retirement, while retirement seems to have a negative effect on the self-assessed experience of health among people with the highest level of education. From a population-health perspective the time has come to consider a made-to-measure age of retirement. PMID- 26675651 TI - [Physician and autonomy: on time perception and job satisfaction]. AB - Is it true that haste is sneaking into medicine? In this article, it is argued that it mainly concerns the perception of being rushed, which is caused by a loss of autonomy of the modern physician. In the fifties, physicians were busy as well, but because they enjoyed a greater degree of autonomy compared to their contemporary colleagues, they did not experience this in a negative way. Due to increased bureaucracy and the introduction of market dynamics, the medical profession has lost autonomy, which in turn led to a loss of job satisfaction. PMID- 26675652 TI - [Time in good health--the holy grail of medicine]. AB - One of the challenges in medicine is to give patients good advice and guidance that will enable them to live for as long as possible in as good a state of health as possible. Prevention of disease is the best treatment. This is why it is so important to accurately predict the risk of various diseases such as cancer, vascular disease or diabetes mellitus. In high-risk patients it is useful to take preventative measures. To do this it is necessary to have information about the expected absolute treatment effect for each individual patient. All this information can then be used in a discussion between the patient and their treating professional so that together they can make an informed decision about whether or not to take preventative measures that are aimed at a longer disease free life. This may or may not mean living longer, but it does mean a life in as good a state of health as possible. PMID- 26675653 TI - [Perspectives of medical specialists on sharing decisions in cancer care: a qualitative study concerning chemotherapy decisions with patients with recurrent glioblastoma]. AB - BACKGROUND: In cancer care, difficult decisions concerning advanced treatment need to be made, weighing possible life prolongation against harmful side effects. Treatment is frequently started, showing the need to explore how decisions are made. Little is known about the perspectives of physicians on sharing decision making with patients. This qualitative study aimed to describe the perspectives of medical specialists on the decision-making process with patients with glioblastoma concerning starting new treatment. METHODS: Qualitative interviews were held with medical specialists. One focus group was organized with medical professionals. Their opinions about elements of shared decision making and the applicability in the context of patients with glioblastoma were assessed. The topic list for the focus group was based on the analysis of the interviews. Qualitative analysis of the transcripts was performed by three researchers independently. RESULTS: Medical specialists considered shared decision making to be important; however, they did not adhere to its elements. Stopping treatment was not considered equal to continuing treatment. Exploration of the patients' wishes was done implicitly, and shared responsibility for the decision was not highly recognized. The main barriers to shared decision making were preferences of both patients and specialists for starting or continuing treatment and assumptions of physicians about knowing what patients want. CONCLUSION: Medical specialists recognized the importance of patient involvement but experienced difficulty in sharing decision making in practice. Elements of shared decision making are partly followed but do not guide decision making. To improve cancer care, education of medical specialists and adjustment to the elements are needed to involve patients. PMID- 26675654 TI - [The years in pictures; medical milestones since 1970]. AB - The end of the year is always a perfect moment to look back. However, looking back over the past year alone is not enough if you want a complete picture of developments in medical science, which is why the Dutch Journal of Medicine (NTvG) has posted a timeline on its website charting medical milestones over the past 45 years. Some of these milestones are illustrated in the infographic in this number, and some interesting patterns can be observed. In this article we discuss various trends, from the increasing tendency to quantify to the rise of evidence-based medicine. PMID- 26675655 TI - The Effect of Addition of an EPS Degrading Enzyme with and without Detergent to 2% Chlorhexidine on Disruption of Enterococcus faecalis Biofilm: A Confocal Laser Scanning Microscopic Study. AB - BACKGROUND: Enterococcus faecalis is one of the most commonly occurring organisms retrieved from root canal treated teeth that show refractory apical periodontitis. Though it is well known that the ability of E. faecalis to form a matrix-encased biofilm contributes to its pathogenicity, the role of extracellular dextran and DNA in biofilm formation and its effect on the susceptibility of the biofilm to chlorhexidine remains poorly understood. It was hypothesized that the addition of an Extracellular Polymeric Substance (EPS) degrading enzyme along with a detergent to chlorhexidine may increase the susceptibility of the E. faecalis biofilm. AIM: To evaluate the sensitivity of Enterococcus faecalis biofilms treated with DNase enzyme and their susceptibility to 2% chlorhexidine used alone or in conjunction with a detergent in a dentin disinfection model and examine under confocal laser scanning microscopy (CLSM). MATERIALS AND METHODS: Semi cylindrical shaped dentin specimens were infected with E. faecalis and incubated for 24 hours. Following incubation, the infected dentin specimens were exposed for 3 minutes to the four disinfecting solutions and grouped accordingly. {Group I- Sterile saline, Group II- 2% Chlorhexidine (CHX), Group III- Dnase1 Enzyme + 2% CHX, Group IV- DNase1 Enzyme + 2% CHX & Tween 80. Bacterial viability was then assessed by staining the specimens and examining under CLSM to analyse the proportion of dead and live bacteria within the dentinal tubules. RESULTS: The Groups II, III and IV showed statistically significant (p<0.05) percentage of dead bacteria compared to the control (Group I). However there was no significant difference in the killing effectiveness within the experimental groups (II-IV) at (p<0.05). CONCLUSION: EPS degrading enzyme (DNase I) disrupts the biofilm and increases the susceptibility of E.faecalis when exposed to 2% Chlorhexidine and the use of a surfactant with this combination significantly contributes to improving the antibacterial efficacy. PMID- 26675658 TI - Correction. AB - [This corrects the article DOI: 10.7860/JCDR/2015/12418.5602.]. PMID- 26675656 TI - Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening. AB - Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A) with mutations in one CH3 domain (CH3A) on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B) with mutations in the other CH3 domain (CH3B). In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90%) with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-pi interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display. PMID- 26675659 TI - Secondary metabolites from Scrophularia canina L. AB - A re-examination of Scrophularia canina L. confirmed the presence of iridoid glucosides considered as chemotaxonomic markers for the Scrophulariaceae family, like aucubin, harpagide and 8-O-acetylharpagide, besides the further presence of 8-epiloganic acid, which is, indeed, considered the biogenetic precursor of iridoids normally found in Scrophulariaceae, and was recognised here for the first time in the studied species. Also verbascoside and (E)-phytol were evidenced for the first time in S. canina. The former compound is an almost ubiquitous glycosidic phenyl-ethanoid, which attains systematic importance when in co-occurrence with iridoids, and its taxonomical implications were discussed. The latter compound, even though it is omnipresent, is interestingly endowed with several biological activities, which may give an additional reason for the traditional uses of this plant. PMID- 26675660 TI - Design of new disulfide-based organic compounds for the improvement of self healing materials. AB - Self-healing materials are a very promising kind of materials due to their capacity to repair themselves. Among others, diphenyl disulfide-based compounds (Ph2S2) appear to be among the best candidates to develop materials with optimum self-healing properties. However, few is known regarding both the reaction mechanism and the electronic structure that make possible such properties. In this vein, theoretical approaches are of great interest. In this work, we have carried out theoretical calculations on a wide set of different disulfide compounds, both aromatic and aliphatic, in order to elucidate the prevalent reaction mechanism and the necessary electronic conditions needed for improved self-healing properties. Two competitive mechanisms were considered, namely, the metathesis and the radical-mediated mechanism. According to our calculations, the radical-mediated mechanism is the responsible for this process. The formation of sulfenyl radicals strongly depends on the S-S bond strength, which can be modulated chemically by the use of proper derivatives. At this point, amino derivatives appear to be the most promising ones. In addition to the S-S bond strength, hydrogen bonding between disulfide chains seems to be relevant to favour the contact among disulfide units. This is crucial for the reaction to take place. The calculated hydrogen bonding energies are of the same order of magnitude as the S-S bond energies. Finally, reaction barriers have been analysed for some promising candidates. Two reaction mechanisms were compared, namely, the [2+2] metathesis reaction mechanism and the [2+1] radical-mediated mechanism. No computational evidence for the existence of any transition state for the metathesis mechanism was found, which indicates that the radical-mediated mechanism is the one responsible in the self-healing process of these materials. Interestingly, the calculated reaction barriers are around 10 kcal mol(-1) regardless the substituent employed. All these results suggest that the radical formation and the structural role of the hydrogen bonding prevale over kinetics. Having this in mind, as a conclusion, some new compounds are proposed for the design of future self-healing materials with improved features. PMID- 26675661 TI - Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial. AB - BACKGROUND: Impaired brain glucose metabolism appears to be a potential pathogenic feature of mild cognitive impairment (MCI). This study examined the potential for increasing circulating ketone bodies through medium chain triglyceride (MCT) supplementation, as a means to beneficially modulate brain homeostasis in subjects with MCI. METHODS: Six participants with MCI were enrolled in a randomized placebo-controlled trial. Participants received 56 g/day of either medium chain triglycerides (MCTs) or placebo for 24 weeks. Serum beta hydroxybutyrate concentrations, apolipoprotein-E4 status, and cognitive assessments were carried out. Due to the small number of participants only the raw scores were examined. RESULTS: Intake of MCT oil increased serum ketone bodies and improved memory, while intake of placebo did not show improvement in any of the cognitive measures tested. CONCLUSIONS: Consumption of 56 g/day of MCTs for 24 weeks increases serum ketone concentrations and appears to be a candidate for larger randomized control trials in the future that quantify the modulation of cognitive function through supplementation with ketone precursors, in patients with MCI. PMID- 26675662 TI - An altered GABA-A receptor function in spinocerebellar ataxia type 6 and familial hemiplegic migraine type 1 associated with the CACNA1A gene mutation. AB - BACKGROUND: Mutations in the CACNA1A gene encoding the voltage-gated calcium channel alpha1A subunit have been identified in patients with autosomal dominantly inherited neurological disorders, including spinocerebellar ataxia type 6 (SCA6) and familial hemiplegic migraine type 1 (FHM1). In order to investigate the underlying pathogenesis common to these distinct phenotypic disorders, this study investigated the neuronal function of the GABAergic system and glucose metabolism in vivo using positron emission tomography (PET). METHODS: Combined PET studies with [(11)C]-flumazenil and [(18)F]-fluorodeoxyglucose (FDG) were performed in three FHM1 patients and two SCA6 patients. [(18)F]-FDG-PET using a three-dimensional stereotactic surface projection analysis was employed to measure the cerebral metabolic rate of glucose (CMRGlc). In addition, the GABA A receptor function was investigated using flumazenil, a selective GABA-A receptor ligand. RESULTS: All patients displayed a significant decrease in CMRGlc and low flumazenil binding in the cerebellum compared with the normal controls. The flumazenil binding in the temporal cortex was also decreased in two FHM1 patients. CONCLUSIONS: Cerebellar glucose hypometabolism and an altered GABA-A receptor function are characteristic of FHM1 and SCA6. GENERAL SIGNIFICANCE: An altered GABA-A receptor function has previously been reported in models of inherited murine cerebellar ataxia caused by a mutation in the CACNA1A gene. This study showed novel clinical characteristics of alteration in the GABA-A receptor in vivo, which may provide clinical evidence indicating a pathological mechanism common to neurological disorders associated with CACNA1A gene mutation. PMID- 26675664 TI - Conservative management of intestinal obstruction by isolated intramural duodenal hematoma. A case report and review of the literature. AB - The duodenal injuries occur in the 3-5% of blunt abdominal traumas. The isolated intramural duodenal hematoma is a very rare lesion. An early diagnosis and an adequate therapy are crucial because a delay, beyond 24 hours, increases the mortality from the 11% to 40%. However, diagnosis is often hindered by a lack of specific symptoms. We report a case of a 21 years-old man with an intestinal obstruction from isolated intramural duodenal hematoma occurred after a blunt abdominal trauma in a sport competition. The patient was treated conservatively with total parenteral nutrition, gastric decompression and intravenous PPIs. The progressive spontaneous resolution of the hematoma was checked with periodical endoscopies. The discharge occurred after three weeks with no early complications. No late complications occurred at one-year follow-up. The endoscopy is a good and safe tool in the management of this intestinal obstructions with the possibility of conservative or interventional treatment. PMID- 26675663 TI - Determinants of Psychosocial Difficulties Experienced by Persons with Brain Disorders: Towards a 'Horizontal Epidemiology' Approach. AB - BACKGROUND: Persons with brain disorders experience significant psychosocial difficulties (PSD) in daily life, e.g. problems with managing daily routine or emotional lability, and the level of the PSD depends on social, physical and political environments, and psychologic-personal determinants. Our objective is to determine a brief set of environmental and psychologic-personal factors that are shared determinants of PSD among persons with different brain disorders. METHODS: Cross-sectional study, convenience sample of persons with either dementia, stroke, multiple sclerosis, epilepsy, migraine, depression, schizophrenia, substance dependence or Parkinson's disease. Random forest regression and classical linear regression were used in the analyses. RESULTS: 722 subjects were interviewed in four European countries. The brief set of determinants encompasses presence of comorbidities, health status appraisal, stressful life events, personality changes, adaptation, self-esteem, self-worth, built environment, weather, and health problems in the family. CONCLUSIONS: The identified brief set of common determinants of PSD can be used to support the implementation of cross-cutting interventions, social actions and policy tools to lower PSD experienced by persons with brain disorders. This set complements a recently proposed reliable and valid direct metric of PSD for brain disorders called PARADISE24. PMID- 26675665 TI - Diagnostic Yield of Universal Urine Toxicology Screening in an Unselected Cohort of Stroke Patients. AB - BACKGROUND: Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA). METHODS: Using a single center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results. RESULTS: Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening-cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01). CONCLUSIONS: Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use. PMID- 26675666 TI - Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus. AB - Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation. PMID- 26675667 TI - EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit. AB - INTRODUCTION: Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). AIM: The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. MATERIALS AND METHODS: A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. RESULT: All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein beta2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. CONCLUSION: Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID- 26675668 TI - Composition Space Analysis in the Development of Copper Molybdate Hybrids Decorated by a Bifunctional Pyrazolyl/1,2,4-Triazole Ligand. AB - A bitopic ligand, 4-(3,5-dimethylpyrazol-4-yl)-1,2,4-triazole (Hpz-tr) (1), containing two different heterocyclic moieties was employed for the design of copper(II)-molybdate solids under hydrothermal conditions. In the multicomponent Cu(II)/Hpz-tr/Mo(VI) system, a diverse set of coordination hybrids, [Cu(Hpz tr)2SO4].3H2O (2), [Cu(Hpz-tr)Mo3O10] (3), [Cu4(OH)4(Hpz-tr)4Mo8O26].6H2O (4), [Cu(Hpz-tr)2Mo4O13] (5), and [Mo2O6(Hpz-tr)].H2O (6), was prepared and characterized. A systematic investigation of these systems in the form of a ternary crystallization diagram approach was utilized to show the influence of the molar ratios of starting reagents, the metal (Cu(II) and Mo(VI)) sources, the temperature, etc., on the reaction products outcome. Complexes 2-4 dominate throughout a wide crystallization range of the composition triangle, while the other two compounds 5 and 6 crystallize as minor phases in a narrow concentration range. In the crystal structures of 2-6, the organic ligand behaves as a short [N N]-triazole linker between metal centers Cu...Cu in 2-4, Cu...Mo in 5, and Mo...Mo in 6, while the pyrazolyl function remains uncoordinated. This is the reason for the exceptional formation of low-dimensional coordination motifs: 1D for 2, 4, and 6 and 2D for 3 and 5. In all cases, the pyrazolyl group is involved in H bonding (H-donor/H-acceptor) and is responsible for pi-pi stacking, thus connecting the chain and layer structures in more complicated H-bonding architectures. These compounds possess moderate thermal stability up to 250-300 degrees C. The magnetic measurements were performed for 2-4, revealing in all three cases antiferromagnetic exchange interactions between neighboring Cu(II) centers and long-range order with a net moment below Tc of 13 K for compound 4. PMID- 26675669 TI - IL-33 reflects dynamics of disease activity in patients with autoimmune hemolytic anemia by regulating autoantibody production. AB - BACKGROUND: Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment. METHODS: Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs. RESULTS: Serum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity. CONCLUSIONS: IL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients. PMID- 26675670 TI - A Computational Study of the Factors Influencing the PVC-Triggering Ability of a Cluster of Early Afterdepolarization-Capable Myocytes. AB - Premature ventricular complexes (PVCs), which are abnormal impulse propagations in cardiac tissue, can develop because of various reasons including early afterdepolarizations (EADs). We show how a cluster of EAD-generating cells (EAD clump) can lead to PVCs in a model of cardiac tissue, and also investigate the factors that assist such clumps in triggering PVCs. In particular, we study, through computer simulations, the effects of the following factors on the PVC triggering ability of an EAD clump: (1) the repolarization reserve (RR) of the EAD cells; (2) the size of the EAD clump; (3) the coupling strength between the EAD cells in the clump; and (4) the presence of fibroblasts in the EAD clump. We find that, although a low value of RR is necessary to generate EADs and hence PVCs, a very low value of RR leads to low-amplitude EAD oscillations that decay with time and do not lead to PVCs. We demonstrate that a certain threshold size of the EAD clump, or a reduction in the coupling strength between the EAD cells, in the clump, is required to trigger PVCs. We illustrate how randomly distributed inexcitable obstacles, which we use to model collagen deposits, affect PVC triggering by an EAD clump. We show that the gap-junctional coupling of fibroblasts with myocytes can either assist or impede the PVC-triggering ability of an EAD clump, depending on the resting membrane potential of the fibroblasts and the coupling strength between the myocyte and fibroblasts. We also find that the triggering of PVCs by an EAD clump depends sensitively on factors like the pacing cycle length and the distribution pattern of the fibroblasts. PMID- 26675672 TI - Human parainfluenza virus type 2 V protein inhibits and antagonizes tetherin. AB - Tetherin (BST-2/CD317/HM1.24) is an antiviral membrane protein that prevents the release of enveloped viruses from the cell surface. We found that the growth of human parainfluenza virus type 2 (hPIV-2), but not that of V protein-deficient recombinant hPIV-2, was inhibited by tetherin. V protein immunoprecipitates with tetherin, and this interaction requires its C-terminal Trp residues. The glycosyl phosphatidylinositol attachment signal of tetherin, but not its cytoplasmic tail, was necessary for its binding with V. The distribution of the V protein clearly changed when co-expressed with tetherin in plasmid-transfected cells. hPIV-2 infection of HeLa cells reduced cell surface tetherin without affecting total cellular tetherin. This reduction also occurred in HeLa cells constitutively expressing V, whereas mutated V protein did not affect the cell surface tetherin. Our results suggest that hPIV-2 V protein antagonizes tetherin by binding it and reducing its presence at the cell surface. PMID- 26675671 TI - Choroidal metastases from thymic carcinoma during pregnancy: Case Report. AB - BACKGROUND: Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma. CASE PRESENTATION: A 28-year old white woman presented with subacute loss of vision in the last trimester of her first pregnancy which was first interpreted as an exacerbation of a pre-existing dermatomyositis and treated with steroids. After failure of steroid therapy choroidal metastases from an undifferentiated thymic carcinoma were diagnosed. This also shed a new light on the dermatomyositis the patient had been suffering from for seven years possibly representing a paraneoplastic syndrome from the tumor. Despite aggressive chemotherapy, the patient died from progressive disease eight years after first onset of dermatomyositis and 14 months after initial diagnosis of the thymic carcinoma. CONCLUSIONS: Choroidal metastases from a thymic carcinoma have never been reported before but should be included into the differential diagnosis of choroidal masses. PMID- 26675673 TI - Warming Ocean Conditions Relate to Increased Trophic Requirements of Threatened and Endangered Salmon. AB - The trophic habits, size and condition of yearling Chinook salmon (Oncorhynchus tshawytscha) caught early in their marine residence were examined during 19 survey years (1981-1985; 1998-2011). Juvenile salmon consumed distinct highly piscivorous diets in cold and warm ocean regimes with major differences between ocean regimes driven by changes in consumption of juvenile rockfishes, followed by several other fish prey, adult euphausiids and decapod larvae. Notable, Chinook salmon consumed 30% more food in the warm versus cold ocean regime in both May and June. Additionally, there were about 30% fewer empty stomachs in the warm ocean regime in May, and 10% fewer in warm June periods. The total prey energy density consumed during the warmer ocean regime was also significantly higher than in cold. Chinook salmon had lower condition factor and were smaller in fork length during the warm ocean regime, and were longer and heavier for their size during the cold ocean regime. The significant increase in foraging during the warm ocean regime occurred concurrently with lower available prey biomass. Adult return rates of juvenile Chinook salmon that entered the ocean during a warm ocean regime were lower. Notably, our long term data set contradicts the long held assertion that juvenile salmon eat less in a warm ocean regime when low growth and survival is observed, and when available prey are reduced. Comparing diet changes between decades under variable ocean conditions may assist us in understanding the effects of projected warming ocean regimes on juvenile Chinook salmon and their survival in the ocean environment. Bioenergetically, the salmon appear to require more food resources during warm ocean regimes. PMID- 26675674 TI - Iron-mineral accretion from acid mine drainage and its application in passive treatment. AB - This study demonstrates substantial removal of iron (Fe) from acid mine drainage (pH ~3) in a passive vertical flow reactor (VFR) with an equivalent footprint of 154 m(2) per L/s mine water and residence times of >23 h. Average Fe removal rate was 67% with a high of 85% over the 10-month trial. The fraction of Fe passing a 0.22 um filter (referred to here as Fe-filt) was seen to be removed in the VFR even when Fe(II) was absent, indicating that the contribution of microbial Fe(II) oxidation and precipitation was not the dominant removal mechanism in the VFR. Removal rates of Fe-filt in the VFR were up to 70% in residence times as low as 8 h compared with laboratory experiments where much smaller changes in Fe-filt were observed over 60 h. Centrifugation indicated that 80-90% of the influent Fe had particle sizes <35 nm. Together with analyses and geochemical modelling, this suggests that the Fe-filt fraction exists as either truly aqueous (but oversaturated) Fe(III) or nanoparticulate Fe(III) and that this metastability persists. When the water was contacted with VFR sludge, the Fe-filt fraction was destabilized, leading to an appreciably higher removal of this fraction. Heterogeneous precipitation and/or aggregation of nanoparticulate Fe(III) precipitates are considered predominant removal mechanisms. Microbial analyses of the mine water revealed the abundance of extracellular polymeric substance generating Fe-oxidizing bacterium 'Ferrovum myxofaciens', which may aid the removal of iron and explain the unusual appearance and physical properties of the sludge. PMID- 26675675 TI - Imidazoquinolines: Recent Developments in Anticancer Activity. AB - Cancer remains one of the unsolved diseases of today's advanced drug discovery world even though it is known to humans for centuries. There is continued effort to discover new chemotherapeutic agents to improve the outcome of cancer patients. Small-molecule agonists at tolllike receptor 7 and 8 (TLR7/8) have recently generated renewed interest in cancer research owing to their profound antitumoral activity. TLR-7/8 agonist imidazoquinolines (Imiquimod, and Resiquimod) and dual inhibitor of phosphoinositide 3-kinase and mammalian target of rapamycin (NVP-BEZ235) have emerged as clinically important candidates for treating cancers. This article reviews briefly the synthesis, structure-activity relationship (SAR) and biological activities of clinically studied imidazoquinolines along with novel emerging preclinical imidazoquinolines for the anticancer activity. PMID- 26675676 TI - Arthroscopic Findings After Traumatic Shoulder Instability in Patients Older Than 35 Years. AB - BACKGROUND: Shoulder instability in the older patient traditionally has received less attention in the literature than in the younger patient population. However, when traumatic dislocation does occur, these patients often still have frequent pain, disability, and even continued instability. PURPOSE: To characterize the pathoanatomy of traumatic anterior shoulder instability in the older patient population and to discuss the correlating symptoms that ultimately led to operative treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with a history of an initial traumatic anterior shoulder instability event occurring after the age of 35 years who underwent arthroscopic surgical intervention were prospectively enrolled. Exclusion criteria included posterior instability, major fractures of the shoulder girdle, and multidirectional instability. All patients initially underwent a period of nonoperative rehabilitation. Operative treatment was performed if a patient continued to have pain and/or instability. Operative reports and arthroscopic pictures were reviewed for pathoanatomical findings. RESULTS: A total of 27 patients (28 shoulders) met the inclusion criteria and were analyzed in this study (22 men and 5 women; mean age, 55 years; age range, 35-74 years). Surgical intervention was performed for recurrent instability in 7 patients, pain for 8 patients, and pain with instability for 13 patients. Arthroscopic findings demonstrated 18 rotator cuff tears (RCTs) (64.3%) and 18 Bankart lesions (64.3%). Nine patients had both an RCT combined with a Bankart lesion (32.1%). Three humeral avulsion of the glenohumeral ligament (HAGL) lesions (10.7%) and 2 anterior labral periosteal sleeve avulsion (ALPSA) lesions (7.1%) were found. All shoulders demonstrated Hill-Sachs lesions of various size and depth. CONCLUSION: Traumatic shoulder instability in the older patient may result in a wide array of pathologic findings as well as a diversity of clinical presentations. These findings suggest that the clinical diagnostician should maintain a high index of suspicion for RCT, Bankart lesions, and HAGL lesions in older patients who remain symptomatic after traumatic anterior shoulder instability. PMID- 26675677 TI - Neoadjuvant Therapy of Gastric Cancer: A Decisive Step Forward. AB - BACKGROUND: Although its incidence has been steadily decreasing in Western countries, gastric cancer remains a leading cause of cancer deaths worldwide. The detection rate of early-stage cancers is improving; nevertheless, the majority of cases is still diagnosed at later stages with a poor prognosis. Furthermore, the results that can be achieved with surgery have reached a plateau of effectiveness. SUMMARY: Neoadjuvant chemotherapy was successfully introduced first in patients with non-curatively resectable disease. In the last decade, neoadjuvant chemotherapy has also been established in potentially curatively resectable cases and has become the state-of-the-art treatment. Esophagogastric junction (EGJ) tumors are not optimally treated with chemotherapy alone, and combined radiochemotherapy (RCT) seems to yield superior outcomes. KEY MESSAGE: The use of neoadjuvant therapy has been successfully established in patients with curatively resectable disease. Neoadjuvant chemotherapy is now a cornerstone in the treatment of gastric cancer and cancer of the EGJ, although further work is needed in order to define the optimal combination regimen. PRACTICAL IMPLICATIONS: Neoadjuvant chemotherapy is currently the gold standard for the treatment of gastric cancer and cancer of the EGJ. Several independent studies have shown the benefits of using combination regimens that included cisplatin and 5-fluorouracil, though recently the use of the EOX (epirubicin, oxaliplatin and capecitabine) regimen has been widely accepted in this setting. Tumors of the EGJ benefit from neoadjuvant treatment with combined RCT. It should be noted that the optimal neoadjuvant regimen in EGJ tumors has not yet been defined, and the survival advantage of neoadjuvant RCT over neoadjuvant chemotherapy remains to be established in this patient population. PMID- 26675678 TI - Vulvar Haematoma Following Laparoscopic Endometrioma Excision: Report of A Rare Complication. AB - Vulvar haematoma as a complication of laparoscopic adnexal surgery has rarely been reported. Indeed, to our knowledge, there are only two case reports describing postlaparoscopic vulvar haematoma in the literature. Although complications associated with laparoscopy are mostly related to bowel or retroperitoneal vessel injury, vulvar haematoma may seldom develop. Vulvar haematoma after laparoscopy may indicate abdominal wall or pelvic vascular injury. We present a case of postoperative vulvar haematoma following laparoscopic endometrioma excision. PMID- 26675680 TI - The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models. AB - Cognitive deficits in various domains, including recognition memory, attention, impulsivity, working memory, and executive function, substantially affect functional outcomes in patients with schizophrenia. TAK-063 [1-[2-fluoro-4-(1H pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a potent and selective phosphodiesterase 10A inhibitor that produces antipsychotic-like effects in rodent models of schizophrenia. We evaluated the effects of TAK-063 on multiple cognitive functions associated with schizophrenia using naive and drug-perturbed rodents. TAK-063 at 0.1 and 0.3 mg/kg p.o. improved time-dependent memory decay in object recognition in naive rats. TAK-063 at 0.1 and 0.3 mg/kg p.o. increased accuracy rate, and TAK-063 at 0.3 mg/kg p.o. reduced impulsivity in a five-choice serial reaction time task in naive rats. N methyl-d-aspartate receptor antagonists, such as phencyclidine and MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine], were used to induce working memory deficits relevant to schizophrenia in animals. TAK 063 at 0.3 mg/kg p.o. attenuated both phencyclidine-induced working memory deficits in a Y-maze test in mice and MK-801-induced working memory deficits in an eight-arm radial maze task in rats. An attentional set-shifting task using subchronic phencyclidine-treated rats was used to assess the executive function. TAK-063 at 0.3 mg/kg p.o. reversed cognitive deficits in extradimensional shifts. These findings suggest that TAK-063 has a potential to ameliorate deficits in multiple cognitive domains impaired in schizophrenia. PMID- 26675681 TI - Blood levels of serotonin are specifically correlated with plasma lysophosphatidylserine among the glycero-lysophospholipids. AB - BACKGROUNDS: Glycero-lysophospholipids (glycero-LPLs), which are known to exert potent biological activities, have been demonstrated to be secreted from activated platelets in vitro; however, their association with platelet activation in vivo has not been yet elucidated. In this study, we investigated the correlations between the blood levels of each glycero-LPL and serotonin, a biomarker of platelet activation, in human subjects to elucidate the involvement of platelet activation in glycero-LPLs in vivo. METHODS AND RESULTS: We measured the plasma serotonin levels in 141 consecutive patients undergoing coronary angiography (acute coronary syndrome, n = 38; stable angina pectoris, n = 71; angiographically normal coronary arteries, n = 32) and investigated the correlations between the plasma levels of serotonin and glycero-LPLs. The results revealed the existence of a specific and significant association between the plasma serotonin and plasma lysophosphatidylserine (LysoPS) levels. On the contrary, regular aspirin intake failed to affect the plasma LysoPS levels despite the fact that the plasma lysophosphatidic acid, lysophosphatidylethanolamine, lysophosphatidylglycerol, and lysophosphatidylinositol levels were lower in those who had taken aspirin regularly. CONCLUSION: We found a specific positive correlation between the blood levels of serotonin and LysoPS, a new lipid mediator. Thus, LysoPS might be specifically involved in strong platelet activation, which is associated with the release of serotonin. GENERAL SIGNIFICANCE: Our present results suggest the possible involvement of LysoPS in the pathogenesis of atherosclerotic diseases. PMID- 26675679 TI - GluN2D N-Methyl-d-Aspartate Receptor Subunit Contribution to the Stimulation of Brain Activity and Gamma Oscillations by Ketamine: Implications for Schizophrenia. AB - The dissociative anesthetic ketamine elicits symptoms of schizophrenia at subanesthetic doses by blocking N-methyl-d-aspartate receptors (NMDARs). This property led to a variety of studies resulting in the now well-supported theory that hypofunction of NMDARs is responsible for many of the symptoms of schizophrenia. However, the roles played by specific NMDAR subunits in different symptom components are unknown. To evaluate the potential contribution of GluN2D NMDAR subunits to antagonist-induced cortical activation and schizophrenia symptoms, we determined the ability of ketamine to alter regional brain activity and gamma frequency band neuronal oscillations in wild-type (WT) and GluN2D knockout (GluN2D-KO) mice. In WT mice, ketamine (30 mg/kg, i.p.) significantly increased [(14)C]-2-deoxyglucose ([(14)C]-2DG) uptake in the medial prefrontal cortex (mPFC), entorhinal cortex and other brain regions, and decreased activity in the somatosensory cortex and inferior colliculus. In GluN2D-KO mice, however, ketamine did not significantly increase [(14)C]-2DG uptake in any brain region examined, yet still decreased [(14)C]-2DG uptake in the somatosensory cortex and inferior colliculus. Ketamine also increased locomotor activity in WT mice but not in GluN2D-KO mice. In electrocorticographic analysis, ketamine induced a 111% +/- 16% increase in cortical gamma-band oscillatory power in WT mice, but only a 15% +/- 12% increase in GluN2D-KO mice. Consistent with GluN2D involvement in schizophrenia-related neurologic changes, GluN2D-KO mice displayed impaired spatial memory acquisition and reduced parvalbumin (PV)-immunopositive staining compared with control mice. These results suggest a critical role of GluN2D containing NMDARs in neuronal oscillations and ketamine's psychotomimetic, dissociative effects and hence suggests a critical role for GluN2D subunits in cognition and perception. PMID- 26675707 TI - Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway. AB - Cellular senescence, an irreversible state of growth arrest, underlies organismal aging and age-related diseases. Recent evidence suggests that aging intervention based on inhibition of cellular senescence might be a promising strategy for treatment of aging and age-related diseases. Embryonic stem cells (ESCs) and ESC conditioned medium (CM) have been suggested as a desirable source for regenerative medicine. However, effects of ESC-CM on cellular senescence remain to be determined. We found that treatment of senescent human dermal fibroblasts with CM from mouse ESCs (mESCs) decreases senescence phenotypes. We found that platelet-derived growth factor BB in mESC-CM plays a critical role in antisenescence effect of mESC-CM through up-regulation of fibroblast growth factor 2. We confirmed that mESC-CM treatment accelerates the wound-healing process by down-regulating senescence-associated p53 expression in in vivo models. Taken together, our results suggest that mESC-CM has the ability to suppress cellular senescence and maintain proliferative capacity. Therefore, this strategy might emerge as a novel therapeutic strategy for aging and age-related diseases. PMID- 26675706 TI - Time-dependent evolution of functional vs. remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation. AB - Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for uncovering disease mechanisms and assessing drugs for efficacy/toxicity. However, the accuracy with which hiPSC-CMs recapitulate the contractile and remodeling signaling of adult cardiomyocytes is not fully known. We used beta-adrenergic receptor (beta-AR) signaling as a prototype to determine the evolution of signaling component expression and function during hiPSC-CM maturation. In "early" hiPSC-CMs (less than or equal to d 30), beta2-ARs are a primary source of cAMP/PKA signaling. With longer culture, beta1-AR signaling increases: from 0% of cAMP generation at d 30 to 56.8 +/- 6.6% by d 60. PKA signaling shows a similar increase: 15.7 +/- 5.2% (d 30), 49.8 +/- 0.5% (d 60), and 71.0 +/- 6.1% (d 90). cAMP generation increases 9-fold from d 30 to 60, with enhanced coupling to remodeling pathways (e.g., Akt and Ca(2+)/calmodulin dependent protein kinase type II) and development of caveolin-mediated signaling compartmentalization. By contrast, cardiotoxicity induced by chronic beta-AR stimulation, a major component of heart failure, develops much later: 5% cell death at d 30vs 55% at d 90. Moreover, beta-AR maturation can be accelerated by biomechanical stimulation. The differential maturation of beta-AR functionalvs remodeling signaling in hiPSC-CMs has important implications for their use in disease modeling and drug testing. We propose that assessment of signaling be added to the indices of phenotypic maturation of hiPSC-CMs.-Jung, G., Fajardo, G., Ribeiro, A. J. S., Kooiker, K. B., Coronado, M., Zhao, M., Hu, D.-Q., Reddy, S., Kodo, K., Sriram, K., Insel, P. A., Wu, J. C., Pruitt, B. L., Bernstein, D. Time-dependent evolution of functionalvs remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation. PMID- 26675708 TI - Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. AB - It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitmentin vitro In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cellsin vivo Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitmentin vivoand that the primary cilium contributes to this process.-Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. PMID- 26675709 TI - Renal Venous Doppler Study in Obstructive Uropathy. AB - INTRODUCTION: Obstructive uropathy is very common cause of pain abdomen. Recognition of the cause of the pain and level of obstruction is the goal. Ultrasound is the primary modality used for detection and characterization of obstructive uropathy along with conventional radiographs. Obstructive uropathy in early stages can be difficult to diagnose using standard B-mode USG or arterial sensitive index. AIM: The purpose of this study is to evaluate the diagnostic accuracy of renal venous doppler ultrasound in diagnosing acute obstructive uropathy either alone or in addition to arterial doppler study of inter lobar arteries. As there is limited literature available till date on Indian population regarding renal venous doppler in obstructive uropathy, this study can be useful. MATERIALS AND METHODS: Fifty patients presenting with features suggestive of obstructive uropathy were studied and compared with non-obstructed kidney of the same patient. Fifty normal individuals were studied and taken as controls. RESULTS: The mean venous impedance index on the obstructed side (0.26 +/- 0.07) was less than the mean venous impedance index on the unobstructed side (0.41 +/- 0.08) and was statistically highly significant. There was no statistically significant difference in mean arterial Resistivity Index (RI). CONCLUSION: Thus renal venous doppler study is a reliable tool in diagnosing cases of acute obstructive uropathy. Though its use as single parameter to identify obstruction still needs further studies, it can be used in conjugation with b mode ultrasound and arterial Doppler to identify obstruction. PMID- 26675710 TI - Ultrasonography in the diagnosis of hemorrhagic cystitis - a complication of bone marrow transplantation in pediatric oncology patients. AB - OBJECTIVE: The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of hemorrhagic cystitis following bone marrow transplantation in children. MATERIAL AND METHODS: The study involved an analysis of clinical material and the results of imaging tests performed in 334 patients who underwent hematopoietic cell transplantation. Ultrasonographic findings in 42 patients with hemorrhagic cystitis were analyzed in detail. The ultrasound images served to assess the severity of hemorrhagic cystitis and the results were compared with the clinical assessment of the disease on the Droller scale, as well as the laboratory and endoscopic tests. RESULTS: In the studied group of patients hemorrhagic cystitis following allogeneic transplantation was diagnosed in 12.5% cases. 73.8% patients received transplants from unrelated donors, 26.2% from compatible siblings. The study revealed a higher incidence of hemorrhagic cystitis in children above 10 years of age. Grade 3 according to the Droller was diagnosed in 42.9%, grade 2 - in 30.9%, grade 4 - in 14.3%, and grade 1 - in 11.9% patients. The number of ultrasound examinations depended on the clinical symptoms, severity, duration and co-occurrence of other complications following the transplantation and was within the 1-15 range (average: 4.6). Grades 3 and 4 were related to the poor clinical condition of the patients and to their longer hospitalization. During this period there was an increased risk of renal malfunction and acute renal failure, post-inflammatory narrowing of the ureters, hydronephrosis, and in grade 4 the fibrosis of the bladder with reduced bladder capacity. Analyses demonstrated a significant correlation between the ultrasound image of the bladder wall and the clinical severity. CONCLUSIONS: Ultrasound with Doppler options remains the primary diagnostic tool in the evaluation of hemorrhagic cystitis, and is useful in terms of its diagnosis, determination of the severity, and monitoring of the treatment. PMID- 26675711 TI - Management of carotid stenosis. History and today. AB - Internal carotid stenosis constitutes a significant clinical challenge, since it is the cause of 20-25% of ischemic brain strokes. The management of the internal carotid stenosis for many years has been raising controversies amongst neurologists, vascular surgeons and interventional radiologists mainly due to the introduction of endovascular stenting as an alternative to surgical treatment. Its application, however, requires knowledge of specific selection criteria for this kind of treatment as well as of the methods of monitoring patients after stent implantation into the internal carotid artery. Duplex Doppler ultrasound examination is currently a basis for the diagnosis of the arterial stenosis of precranial segments of the carotid arteries. It allows a reliable assessment of not only the course and morphology of the walls, but also of the hemodynamics of blood flow. Interventional treatment is applicable in patients with internal carotid stenosis of >=70%, which is accompanied by an increase of the systolic flow velocity above 200 cm/s and the end-diastolic velocity above 50-60 cm/s in the stenotic lumen. In most cases, such a diagnosis in duplex Doppler ultrasound examination does not require any confirmation by additional diagnostic methods and if neurological symptoms are also present, it constitutes a single indication for interventional treatment. When deciding about choice of surgical or endovascular method of treatment, the following factors are of crucial importance: morphology of atherosclerotic plaque, its size, echogenicity, homogeneity of its structure, its surface and outlines. By means of ultrasound examinations, patients can be monitored after endovascular stent implantation. They enable evaluation of the degree of stent patency and allow for an early detection of symptoms indicating stenosis recurrence or presence of in-stent thrombosis. When interpreting the findings of the US checkup, it is essential to refer to the initial examination performed in the first days after the procedure and the next ones conducted during the monitoring period. PMID- 26675712 TI - Downregulation of microRNA-132 by DNA hypermethylation is associated with cell invasion in colorectal cancer. AB - microRNAs (miRNAs) are small, noncoding RNAs that are involved in many biological processes, and aberrant regulation of miRNAs is always associated with cancer progression and development. Abnormal expression of miRNA-132 (miR-132) has been found in some types of cancer, but the effects and potential mechanisms of miR 132 in colorectal cancer (CRC) have not been explored to date. In this study, quantitative real-time polymerase chain reaction was used to investigate the level of miR-132 in CRC tissues and their paired adjacent normal tissues. Bioinformatics analysis indicated that the mechanism underlying the tumor suppressor role of miR-132 in CRC cells may play a role in tumor suppression by targeting paxillin. Furthermore, methylation-specific polymerase chain reaction was performed to evaluate the methylation status of the miR-132 regulatory region. A DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, was used to activate the expression of miR-132 in CRC cells in vitro. Downregulation of miR 132 may occur as a result of hypermethylation and implies a poor prognosis in CRC; therefore, triggering miR-132 reexpression by using DNA methyltransferase inhibitors may be a potential molecular therapeutic target for CRC. PMID- 26675714 TI - Muscles - histology, micro/macroanatomy and US anatomy, a brand new perspective. PMID- 26675713 TI - Hypercalcemia of malignancy and new treatment options. AB - Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25 dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient's symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappaB ligand, and the calcimimetic cinacalcet. Finally, anti PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory cancer with survival on the order of months. PMID- 26675715 TI - beta-Asarone modulate adipokines and attenuates high fat diet-induced metabolic abnormalities in Wistar rats. AB - Here we investigated the effect of beta-asarone on food preference and its therapeutic potential against high fat diet (HFD) induced obesity in rats. In food preference study, free access to HFD was given only for 4h in addition to standard laboratory chow in rats and the preferential intake between chow and HFD was measured. For obesity induction, HFD was administered for 12 weeks and the HFD fed rats were treated with beta-asarone in the last 4 weeks, starting from 9th week onwards. Food intake, body weight was measured biweekly. Glucose tolerance and the levels of glucose, lipids, free fatty acids, leptin, and adiponectin were assessed. HFD fed rats showed progressive increase in body weight and developed glucose intolerance and dyslipidemia. In addition, they showed increased adiposity and the disturbed pattern of adipokine levels In the food preference paradigm, beta-asarone produced selective decrease in HFD intake in rats. In obese rats, beta-asarone treatment not only reduced body weight but also prevented HFD-induced metabolic alterations, including glucose intolerance, dyslipidemia and adipokine imbalance. The observed beneficial effects of beta asarone appear due its ability to reduce intake of energy dense food by affecting food palatability, and to normalize the levels of leptin and adiponectin in rats. Overall, our results suggest that beta-asarone is a novel candidate molecule with significant therapeutic potential in the management of obesity and associated abnormalities. PMID- 26675716 TI - Using surface plasmon resonance spectroscopy to characterize the inhibition of NGF-p75(NTR) and proNGF-p75(NTR) interactions by small molecule inhibitors. AB - Nerve growth factor (NGF), a member of the neurotrophin family, acts to influence the survival and differentiation of neurons in both the central and peripheral nervous systems via its binding to the p75(NTR) and TrkA receptors. Its precursor, proNGF, has been shown to be the dominant form of NGF in the central nervous system, suggesting a biological function beyond its role as a precursor. Like NGF, proNGF is known to bind the p75(NTR) receptor. The dysregulation of both NGF and proNGF have been implicated in several pathologies, including neurodegenerative diseases linked to p75(NTR)-mediated apoptotic signaling. Therefore, the identification of small molecule inhibitors capable of inhibiting both NGF and proNGF-p75(NTR) interactions may be of therapeutic interest. In the present study, we examine the inhibitory action of known small molecule-based inhibitors PD90780, ALE-0540, Ro 08-2750, and PQC 083, as well as novel derivatives of these compounds, using surface plasmon resonance (SPR) spectroscopy. PMID- 26675717 TI - Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer. AB - Triple negative breast cancer (TNBC) accounts for approximately 15-20% of all types of breast cancer, and treatment is still limited. This type of breast cancer shows a high risk of recurrence, visceral metastasis, a worse prognosis, and shorter distant metastasis-free survival. Several studies have been reported that genetics factors are associated with breast cancer disease progression and patients' survival. In this study, we combined Taiwanese microarray data from the GEO database and The Cancer Genome Atlas (TCGA) database to study the role of Integrin Beta1 (ITGB1) in TNBC. Two triple negative breast cancer cell lines (MDA MB-231; MDA-MB-468) were used to validate the functions of ITGB1. We found that a higher ITGB1 gene expression level was associated to lower survival. Silencing of ITGB1 inhibited TNBC cell migration, invasion and store-operated calcium influx. Our study provided a potential candidate biomarker for breast cancer cells migration, invasion and TNBC patients' survival. PMID- 26675718 TI - Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice. AB - In the present study we investigated the role of sodium butyrate (butyrate), and its more palatable derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), in animal models of acute and chronic pain. We found that oral administrations of butyrate (10-200mg/Kg) or equimolecular FBA (21.2-424mg/Kg) reduced visceral pain in a dose- and time-dependent manner. Both drugs were also effective in the formalin test, showing an antinociceptive effect. This analgesic effect was blocked by glibenclamide, suggesting the involvement of ATP-dependent K(+) channels. Moreover, following repeated administration butyrate (100 200mg/Kg) and FBA (212-424mg/Kg) retained their analgesic properties in a model of neuropathic pain, reducing mechanical and thermal hyperalgesia in the chronic constriction injury (CCI) model. The involvement of peroxisome proliferator activated receptor (PPAR) -alpha and -gamma for the analgesic effect of butyrate was also investigated by using PPAR-alpha null mice or the PPAR-gamma antagonist GW9662. Western blot analysis, confirmed the role of peroxisome receptors in butyrate effects, evidencing the increase of PPAR-alpha and -gamma expression, associated to the reduction of inflammatory markers (COX-2, iNOS, TNF-alpha and cFOS). In conclusion, we describe the role of butyrate-based drugs in pain, identifying different and converging non-genomic and genomic mechanisms of action, which cooperate in nociception maintenance. PMID- 26675719 TI - Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding site. AB - Variant rs351855-G/A is a commonly occurring single-nucleotide polymorphism of coding regions in exon 9 of the fibroblast growth factor receptor FGFR4 (CD334) gene (c.1162G>A). It results in an amino-acid change at codon 388 from glycine to arginine (p.Gly388Arg) in the transmembrane domain of the receptor. Despite compelling genetic evidence for the association of this common variant with cancers of the bone, breast, colon, prostate, skin, lung, head and neck, as well as soft-tissue sarcomas and non-Hodgkin lymphoma, the underlying biological mechanism has remained elusive. Here we show that substitution of the conserved glycine 388 residue to a charged arginine residue alters the transmembrane spanning segment and exposes a membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3) binding site Y(390)-(P)XXQ(393). We demonstrate that such membrane-proximal STAT3 binding motifs in the germline of type I membrane receptors enhance STAT3 tyrosine phosphorylation by recruiting STAT3 proteins to the inner cell membrane. Remarkably, such germline variants frequently co-localize with somatic mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo. Thus, our findings elucidate the molecular mechanism behind the genetic association of rs351855 with accelerated cancer progression and suggest that germline variants of cell-surface molecules that recruit STAT3 to the inner cell membrane are a significant risk for cancer prognosis and disease progression. PMID- 26675720 TI - Corrigendum: Failure to replicate the STAP cell phenomenon. PMID- 26675722 TI - Network-analysis-guided synthesis of weisaconitine D and liljestrandinine. AB - General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three families of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites. PMID- 26675721 TI - DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. AB - T helper 17 (TH17) lymphocytes protect mucosal barriers from infections, but also contribute to multiple chronic inflammatory diseases. Their differentiation is controlled by RORgammat, a ligand-regulated nuclear receptor. Here we identify the RNA helicase DEAD-box protein 5 (DDX5) as a RORgammat partner that coordinates transcription of selective TH17 genes, and is required for TH17 mediated inflammatory pathologies. Surprisingly, the ability of DDX5 to interact with RORgammat and coactivate its targets depends on intrinsic RNA helicase activity and binding of a conserved nuclear long noncoding RNA (lncRNA), Rmrp, which is mutated in patients with cartilage-hair hypoplasia. A targeted Rmrp gene mutation in mice, corresponding to a gene mutation in cartilage-hair hypoplasia patients, altered lncRNA chromatin occupancy, and reduced the DDX5-RORgammat interaction and RORgammat target gene transcription. Elucidation of the link between Rmrp and the DDX5-RORgammat complex reveals a role for RNA helicases and lncRNAs in tissue-specific transcriptional regulation, and provides new opportunities for therapeutic intervention in TH17-dependent diseases. PMID- 26675723 TI - Exceptional preservation of tiny embryos documents seed dormancy in early angiosperms. AB - The rapid diversification of angiosperms through the Early Cretaceous period, between about 130-100 million years ago, initiated fundamental changes in the composition of terrestrial vegetation and is increasingly well understood on the basis of a wealth of palaeobotanical discoveries over the past four decades and their integration with improved knowledge of living angiosperms. Prevailing hypotheses, based on evidence both from living and from fossil plants, emphasize that the earliest angiosperms were plants of small stature with rapid life cycles that exploited disturbed habitats in open, or perhaps understorey, conditions. However, direct palaeontogical data relevant to understanding the seed biology and germination ecology of Early Cretaceous angiosperms are sparse. Here we report the discovery of embryos and their associated nutrient storage tissues in exceptionally well-preserved angiosperm seeds from the Early Cretaceous. Synchrotron radiation X-ray tomographic microscopy of the fossil embryos from many taxa reveals that all were tiny at the time of dispersal. These results support hypotheses based on extant plants that tiny embryos and seed dormancy are basic for angiosperms as a whole. The minute size of the fossil embryos, and the modest nutrient storage tissues dictated by the overall small seed size, is also consistent with the interpretation that many early angiosperms were opportunistic, early successional colonizers of disturbance-prone habitats. PMID- 26675725 TI - Ecology: Different worlds. PMID- 26675724 TI - The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. AB - Insulin/insulin-like growth factor signalling (IIS) is a critical regulator of an organism's most important biological decisions from growth, development, and metabolism to reproduction and longevity. It primarily does so through the activity of the DAF-16 transcription factor (forkhead box O (FOXO) homologue), whose global targets were identified in Caenorhabditis elegans using whole-worm transcriptional analyses more than a decade ago. IIS and FOXO also regulate important neuronal and adult behavioural phenotypes, such as the maintenance of memory and axon regeneration with age, in both mammals and C. elegans, but the neuron-specific IIS/FOXO targets that regulate these functions are still unknown. By isolating adult C. elegans neurons for transcriptional profiling, we identified both the wild-type and IIS/FOXO mutant adult neuronal transcriptomes for the first time. IIS/FOXO neuron-specific targets are distinct from canonical IIS/FOXO-regulated longevity and metabolism targets, and are required for extended memory in IIS daf-2 mutants. The activity of the forkhead transcription factor FKH-9 in neurons is required for the ability of daf-2 mutants to regenerate axons with age, and its activity in non-neuronal tissues is required for the long lifespan of daf-2 mutants. Together, neuron-specific and canonical IIS/FOXO-regulated targets enable the coordinated extension of neuronal activities, metabolism, and longevity under low-insulin signalling conditions. PMID- 26675726 TI - Corrigendum: Gigantism and comparative life-history parameters of tyrannosaurid dinosaurs. PMID- 26675727 TI - Corrigendum: Hallmarks of pluripotency. PMID- 26675728 TI - Substantial contribution of extrinsic risk factors to cancer development. AB - Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health. PMID- 26675729 TI - Exploring the repeat protein universe through computational protein design. AB - A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 degrees C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 A. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. PMID- 26675731 TI - Corrigendum: Dinosaurian growth patterns and rapid avian growth rates. PMID- 26675730 TI - Holocene shifts in the assembly of plant and animal communities implicate human impacts. AB - Understanding how ecological communities are organized and how they change through time is critical to predicting the effects of climate change. Recent work documenting the co-occurrence structure of modern communities found that most significant species pairs co-occur less frequently than would be expected by chance. However, little is known about how co-occurrence structure changes through time. Here we evaluate changes in plant and animal community organization over geological time by quantifying the co-occurrence structure of 359,896 unique taxon pairs in 80 assemblages spanning the past 300 million years. Co-occurrences of most taxon pairs were statistically random, but a significant fraction were spatially aggregated or segregated. Aggregated pairs dominated from the Carboniferous period (307 million years ago) to the early Holocene epoch (11,700 years before present), when there was a pronounced shift to more segregated pairs, a trend that continues in modern assemblages. The shift began during the Holocene and coincided with increasing human population size and the spread of agriculture in North America. Before the shift, an average of 64% of significant pairs were aggregated; after the shift, the average dropped to 37%. The organization of modern and late Holocene plant and animal assemblages differs fundamentally from that of assemblages over the past 300 million years that predate the large-scale impacts of humans. Our results suggest that the rules governing the assembly of communities have recently been changed by human activity. PMID- 26675732 TI - A continuum from clear to cloudy hot-Jupiter exoplanets without primordial water depletion. AB - Thousands of transiting exoplanets have been discovered, but spectral analysis of their atmospheres has so far been dominated by a small number of exoplanets and data spanning relatively narrow wavelength ranges (such as 1.1-1.7 micrometres). Recent studies show that some hot-Jupiter exoplanets have much weaker water absorption features in their near-infrared spectra than predicted. The low amplitude of water signatures could be explained by very low water abundances, which may be a sign that water was depleted in the protoplanetary disk at the planet's formation location, but it is unclear whether this level of depletion can actually occur. Alternatively, these weak signals could be the result of obscuration by clouds or hazes, as found in some optical spectra. Here we report results from a comparative study of ten hot Jupiters covering the wavelength range 0.3-5 micrometres, which allows us to resolve both the optical scattering and infrared molecular absorption spectroscopically. Our results reveal a diverse group of hot Jupiters that exhibit a continuum from clear to cloudy atmospheres. We find that the difference between the planetary radius measured at optical and infrared wavelengths is an effective metric for distinguishing different atmosphere types. The difference correlates with the spectral strength of water, so that strong water absorption lines are seen in clear-atmosphere planets and the weakest features are associated with clouds and hazes. This result strongly suggests that primordial water depletion during formation is unlikely and that clouds and hazes are the cause of weaker spectral signatures. PMID- 26675733 TI - Corrigendum: Mapping tree density at a global scale. PMID- 26675734 TI - Competition between DNA methylation and transcription factors determines binding of NRF1. AB - Eukaryotic transcription factors (TFs) are key determinants of gene activity, yet they bind only a fraction of their corresponding DNA sequence motifs in any given cell type. Chromatin has the potential to restrict accessibility of binding sites; however, in which context chromatin states are instructive for TF binding remains mainly unknown. To explore the contribution of DNA methylation to constrained TF binding, we mapped DNase-I-hypersensitive sites in murine stem cells in the presence and absence of DNA methylation. Methylation-restricted sites are enriched for TF motifs containing CpGs, especially for those of NRF1. In fact, the TF NRF1 occupies several thousand additional sites in the unmethylated genome, resulting in increased transcription. Restoring de novo methyltransferase activity initiates remethylation at these sites and outcompetes NRF1 binding. This suggests that binding of DNA-methylation-sensitive TFs relies on additional determinants to induce local hypomethylation. In support of this model, removal of neighbouring motifs in cis or of a TF in trans causes local hypermethylation and subsequent loss of NRF1 binding. This competition between DNA methylation and TFs in vivo reveals a case of cooperativity between TFs that acts indirectly via DNA methylation. Methylation removal by methylation insensitive factors enables occupancy of methylation-sensitive factors, a principle that rationalizes hypomethylation of regulatory regions. PMID- 26675735 TI - Rational design of alpha-helical tandem repeat proteins with closed architectures. AB - Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks. The overall architecture of tandem repeat protein structures--which is dictated by the internal geometry and local packing of the repeat building blocks--is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed alpha-solenoid repeat structures (alpha-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the amino (N) and carboxy (C) termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed alpha-solenoid repeats with a left-handed helical architecture that--to our knowledge--is not yet present in the protein structure database. PMID- 26675738 TI - Shingles is linked to increased risk of cardiovascular events. PMID- 26675736 TI - Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. AB - Parasitic helminths and allergens induce a type 2 immune response leading to profound changes in tissue physiology, including hyperplasia of mucus-secreting goblet cells and smooth muscle hypercontractility. This response, known as 'weep and sweep', requires interleukin (IL)-13 production by tissue-resident group 2 innate lymphoid cells (ILC2s) and recruited type 2 helper T cells (TH2 cells). Experiments in mice and humans have demonstrated requirements for the epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 in the activation of ILC2s, but the sources and regulation of these signals remain poorly defined. In the small intestine, the epithelium consists of at least five distinct cellular lineages, including the tuft cell, whose function is unclear. Here we show that tuft cells constitutively express IL-25 to sustain ILC2 homeostasis in the resting lamina propria in mice. After helminth infection, tuft-cell-derived IL-25 further activates ILC2s to secrete IL-13, which acts on epithelial crypt progenitors to promote differentiation of tuft and goblet cells, leading to increased frequencies of both. Tuft cells, ILC2s and epithelial progenitors therefore comprise a response circuit that mediates epithelial remodelling associated with type 2 immunity in the small intestine, and perhaps at other mucosal barriers populated by these cells. PMID- 26675739 TI - The Impact of Veteran Status on Life-Space Mobility among Older Black and White Men in the Deep South. AB - OBJECTIVE: To examine life-space mobility over 8.5 years among older Black and White male veterans and non-veterans in the Deep South. DESIGN: A prospective longitudinal study of community-dwelling Black and White male adults aged >65 years (N=501; mean age=74.9; 50% Black and 50% White) enrolled in the University of Alabama at Birmingham (UAB) Study of Aging. Data from baseline in-home assessments with follow-up telephone assessments of life-space mobility completed every 6 months were used in linear mixed-effects modeling analyses to examine life-space mobility trajectories. MAIN OUTCOME MEASURES: Life-space mobility. RESULTS: In comparison to veterans, non-veterans were more likely to be Black, single, and live in rural areas. They also reported lower income and education. Veterans had higher baseline life-space (73.7 vs 64.9 for non-veterans; P<.001). Race-veteran subgroup analyses revealed significant differences in demographics, comorbidity, cognition, and physical function. Relative to Black veterans, there were significantly greater declines in life-space trajectories for White non veterans (P=.009), but not for White veterans (P=.807) nor Black non-veterans (P=.633). Mortality at 8.5 years was 43.5% for veterans and 49.5% for non veterans (P=.190) with no significant differences by race-veteran status. CONCLUSIONS: Veterans had significantly higher baseline life-space mobility. There were significantly greater declines in life-space trajectories for White non-veterans in comparison to other race-veteran subgroups. Black veterans and non-veterans did not have significantly different trajectories. PMID- 26675740 TI - Click, Click. PMID- 26675741 TI - Women's Expectations for Breast Cancer Prevention and Early Detection: High Expectations Can Be Achieved. PMID- 26675743 TI - Ultrasound quiz. PMID- 26675742 TI - Outcomes and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Carcinomas. AB - BACKGROUND: Outcomes vary among patients with radioiodine refractory (RR) differentiated thyroid cancer (DTC). The prognostic factors for survival are not well-known, resulting in difficulty in selecting patients for new targeted therapies. We assessed overall survival (OS) and cancer-specific survival (CSS) from RR-DTC to identify prognostic factors associated with survival. PATIENTS AND METHODS: The data on all cases of metastatic RR-DTC treated in our center from 1990 to 2011 were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method; associated prognostic factors were assessed using Cox's model. RESULTS: Of 153 cases of metastatic DTC, 59% (n = 91) met a criterion for RR: that is, 60% (n = 55) had at least 1 metastasis without (131)I uptake; 21% (n = 19) had progressive disease (PD) despite (131)I; 19% (n = 17) had persistent disease despite a cumulative activity of (131)I of >=600 mCi. After the diagnosis of RR, median OS was 8.9 years (95% confidence interval [CI]: 5.4-NR); median CSS was 9.6 years (95% CI: 6.01-NR). In multivariate analyses, PD despite (131)I as a criterion for RR disease and the time from initial diagnosis of DTC to diagnosis of RR <3 years were the only independent prognostic factors for poor OS and CSS. Thyroglobulin doubling time (Tg-DT) was assessed in 31 of 91 cases. Among the 11 patients with Tg-DT for <1 year or undetectable Tg, 6 deaths occurred, whereas only 3 died of 20 patients with Tg-DT >1 year or negative Tg-DT. CONCLUSION: The identification of prognostic factors for decreased survival in RR-DTC may improve the selection of patients for targeted agents. IMPLICATIONS FOR PRACTICE: This study shows a great heterogeneity in terms of prognosis in radioiodine refractory differentiated thyroid carcinoma. Poorer prognosis is observed in patients with tumor progression or with a diagnosis of radioiodine resistance within 3 years after the initial diagnosis of thyroid cancer. Those findings could lead to improvements in the selection of patients for targeted therapies. PMID- 26675744 TI - Efficient Activation of High-Loading Sulfur by Small CNTs Confined Inside a Large CNT for High-Capacity and High-Rate Lithium-Sulfur Batteries. AB - Sulfur with a high specific capacity of 1673 mAh g(-1) is yet to be used as commercial cathode for lithium batteries because of its low utilization rate and poor cycle stability. In this work, a tube-in-tube carbon structure is demonstrated to relieve the critical problems with sulfur cathode: poor electrical conductivity, dissolution of lithium polysulfides, and large volume change during cycling. A number of small carbon nanotubes (~20 nm in diameter) and a high loading amount of 85.2 wt % sulfur are both filled completely inside a large amorphous carbon nanotube (~200 nm in diameter). Owing to the presence of these electrically conductive, highly flexible and structurally robust small CNTs and a large CNT overlayer, sulfur material exhibits a high utilization rate and delivers a large discharge capacity of 1633 mAh g(-1) (based on the mass of sulfur) at 0.1 C, approaching its theoretical capacity (1673 mAh g(-1)). The obtained S-CNTs@CNT electrode demonstrates superior high-rate cycling performances. Large discharge capacities of ~1146, 1121, and 954 mAh g(-1) are observed after 150 cycles at large current rates of 1, 2, and 5 C, respectively. PMID- 26675745 TI - Spontaneous aortic pseudoaneurysm rupture into the sigmoid colon in Behcet's disease patient. AB - Behcet's disease (BD) is a multisystem autoimmune disorder characterized by recurrent orogenital ulcers, uveitis, and skin lesions. The vascular manifestations include thrombophlebitis, stenosis, occlusion, and pseudoaneurysm. BD infrequently precipitates aortic pseudoaneurysm rupture into the sigmoid mesocolon and lumen of the adjacent colon. Here we report an extremely rare case of spontaneous abdominal aortic pseudoaneurysm rupture via the sigmoid mesocolon into the lumen of the sigmoid colon in a 37-year-old patient with BD. PMID- 26675746 TI - Mechanistic Insights into the Initiation Step of the Base Promoted Direct C-H Arylation of Benzene in the Presence of Additive. AB - The direct arylation of unactivated arenes is a very practical and highly convenient procedure for the construction of biaryl scaffolds. Recently, a direct arylation of unactivated benzene has been achieved in the presence of base (tBuOK or tBuONa) and organic additive such as 1,10-phenanthroline. However, details of intimate mechanism of reaction as well as the role of additive have remained elusive until date. The present work explores various mechanistic possibilities of the key electron transfer step of the reaction in order to identify a probable route for the initiation of phenyl radical from iodobenzene. A detailed DFT (M06 2X functional) investigation indicates that the reaction of additive and base can be crucial to generate an electron acceptor-donor pair that can facilitate electron transfer mechanism. This computational model provides a satisfactory explanation for experimental observations, clearly defining the roles of additive and base in the reaction. PMID- 26675747 TI - Synthesis of heavy hydrocarbons at the core-mantle boundary. AB - The synthesis of complex organic molecules with C-C bonds is possible under conditions of reduced activity of oxygen. We have found performing ab initio molecular dynamics simulations of the C-O-H-Fe system that such conditions exist at the core-mantle boundary (CMB). H2O and CO2 delivered to the CMB by subducting slabs provide a source for hydrogen and carbon. The mixture of H2O and CO2 subjected to high pressure (130 GPa) and temperature (4000 to 4500 K) does not lead to synthesis of complex hydrocarbons. However, when Fe is added to the system, C-C bonds emerge. It means that oil might be a more abundant mineral than previously thought. PMID- 26675748 TI - A Rare Case Report of Conjunctival Cyst. AB - A conjunctival cyst is a thin-walled sac or vesicle that contains fluid. This vesicle may develop either on or under the conjunctiva. It develops due to variety of causes such as infection, inflammation, retention cyst and rarely drug induced. The authors aimed to report a case of conjuctival cyst in a 34-year-old male following instillation of anti-allergic topical drugs for over period of one year. Conjuctival cyst developing due to chronic use of anti-allergic topical drugs containing preservatives is one of the complications associated with it. Presence of a preservative in an ocular medication has often been considered in damaging the epithelium. Inclusion of a preservative is equally necessary, especially in multiple-drug therapy in order to protect against dangerous organisms accidentally gaining access during instillation. Benzalkonium chloride (BAK), chlorobutanol, chlorhexidine acetate (CHA) and phenylmercuric nitrate or acetate are some commonly used preservatives in eye drops. PMID- 26675749 TI - Assessment of the utility of ultrasonography with high-frequency transducers in the diagnosis of posttraumatic neuropathies. AB - The primary aim of this paper was to assess the relevance of high-frequency ultrasound examination in qualifying patients for either surgical or conservative treatment of posttraumatic peripheral neuropathies. The study was conducted in a group of 47 patients aged 16-65 (mean age 33) who in 2009-2011 were referred to ultrasound examinations due to a clinical suspicion of posttraumatic peripheral neuropathies. The group included 30 females and 17 males. The patients examined presented with neuropathies of the following peripheral nerves: median, ulnar, common peroneal, digital, cutaneous in the deltoid area, mental, PIN and RSNR. In 21 patients, nerve injuries were partial, and in 24 - complete. In 2 cases, the nerve was entrapped between bony fragments. 17 of 21 patients with partial nerve injuries (80.95%) underwent an EMG examination. No functional tests were conducted in the cases of complete injuries when ultrasound imaging had confirmed the result of the clinical examination. All patients underwent the interview, physical examination and ultrasound examination. Ultrasound examinations were performed with Esaote MyLab 50 and MyLab 60 systems using high-frequency broadband linear transducers: 6-18 MHz. The nerves were evaluated in the gray scale and in the power Doppler mode in longitudinal and transverse sections for localization, morphology and the grade of injury as well as for possible anatomic variants of the nerve trunk and pathologies of the adjacent tissues. Moreover, a dynamic examination was performed, and it was attempted to induce pain or paresthesia by palpation at the site of the visualized pathology. Additionally, the motor and sensory-motor nerves were assessed indirectly based on the images of the skeletal muscles innervated by these nerves. The analyses of the collected material were performed by means of descriptive statistics. The results of clinical and surgical verification were consistent with ultrasound findings in 100% of cases. The results obtained indicate that high-frequency ultrasonography is a valuable method in qualifying patients for various types of treatment of peripheral neuropathies resulting from trauma. PMID- 26675750 TI - Flow perfusion culture of MC3T3-E1 osteogenic cells on gradient calcium polyphosphate scaffolds with different pore sizes. AB - Calcium polyphosphate is a biodegradable bone substitute. It remains a challenge to prepare porous calcium polyphosphate with desired gradient porous structures. In this study, a modified one-step gravity sintering method was used to prepare calcium polyphosphate scaffolds with desired-gradient-pore-size distribution. The differences of porous structure, mechanical strength, and degradation rate between gradient and homogenous calcium polyphosphate scaffolds were evaluated by micro-computed tomography, scanning electron microscopy, and mechanical testing. Preosteoblastic MC3T3-E1 cells were seeded onto gradient and homogenous calcium polyphosphate scaffolds and cultured in a flow perfusion bioreactor. The distribution, proliferation, and differentiation of the MC3T3-E1 cells were compared to that of homogenous calcium polyphosphate scaffolds. Though no significant difference of cell proliferation was found between the gradient and the homogenous calcium polyphosphate scaffolds, a much higher cell differentiation and mineralization were observed in the gradient calcium polyphosphate scaffolds than that of the homogenous calcium polyphosphate scaffolds, as manifested by increased alkaline phosphatase activity (p < 0.05). The improved distribution and differentiation of cultured cells within gradient scaffolds were further supported by both (18)F-fluorine micro-positron emission tomography scanning and in vitro tetracycline labeling. We conclude that the calcium polyphosphate scaffold with gradient pore sizes enhances osteogenic cell differentiation as well as mineralization. The in vivo performance of gradient calcium polyphosphate scaffolds warrants further investigation in animal bone defect models. PMID- 26675751 TI - Stimulation of apoptotic pathways in liver cancer cells: An alternative perspective on the biocompatibility and the utility of biomedical glasses. AB - A host of research opportunities with innumerable clinical applications are open to biomedical glasses if one considers their potential as therapeutic inorganic ion delivery systems. Generally, applications have been limited to repair and regeneration of hard tissues while compositions are largely constrained to the original bioactive glass developed in the 1960s. However, in oncology applications the therapeutic paradigm shifts from repair to targeted destruction. With this in mind, the composition-structure-property-function relationships of vanadium-containing zinc-silicate glasses (0.51SiO2-0.29Na2O-(0.20-X)ZnO-XV2O5, 0 <= X <= 0.09) were characterized in order to determine their potential as therapeutic inorganic ion delivery systems. Increased V2O5mole fraction resulted in a linear decrease in density and glass transition temperature (Tg).(29)Si MAS NMR peak maxima shifted upfield while(51)V MAS NMR peak maxima were independent of V2O5content and overlapped well with the spectra NaVO3 Increased V2O5mole fraction caused ion release to increase. When human liver cancer cells, HepG2, were exposed to these ions they demonstrated a concentration-dependent cytotoxic response, mediated by apoptosis. This work demonstrates that the zinc-silicate system studied herein is capable of delivering therapeutic inorganic ions at concentrations that induce apoptotic cell death and provide a simple means to control therapeutic inorganic ion delivery. PMID- 26675753 TI - On the interpretation of risk and rate advancement periods. AB - Risk and rate advancement periods (RAP) measure the impact of an exposure on the relation of age to disease. Specifically, they quantify the time by which the risk or rate of a disease is advanced among exposed subjects conditional on disease-free survival to a certain baseline age. The fact that these measures incorporate timing of disease occurrence makes them appealing for risk communication, and their use has increased over recent years. Unfortunately, their misinterpretations have also increased. In particular, RAP is often misinterpreted as the difference in mean survival time, when in fact it is a distinct concept and a profoundly different quantity. Other misinterpretations include interpreting RAP as the time by which a survival curve is shifted between exposed and unexposed, and equating RAP to a simple function of relative risks. In this paper we review RAP and show why common misinterpretations are flawed. We also show how RAP is profoundly sensitive to the specification of disease dependence on age. We conclude that whereas RAP remains a potentially useful measure, it requires multiple cautions beyond those needed for traditional measures of association, especially when computed for rates. PMID- 26675752 TI - Socioeconomic disadvantage and neural development from infancy through early childhood. AB - BACKGROUND: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. METHODS: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. RESULTS: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. CONCLUSIONS: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility. PMID- 26675754 TI - The role of magnesium and thyroid function in early pregnancy after in-vitro fertilization (IVF): New aspects in endocrine physiology. AB - BACKGROUND: The initiation of a pregnancy is a process that requires adequate energetic support. Recent observations at our Institution suggest a central role of magnesium in this situation. The aim of this study was to evaluate magnesium, zinc, selenium and thyroid function as well as anti-Mullerian hormone in early pregnancy following in-vitro fertilization as compared to spontaneous successful pregnancies. RESULTS: A successful outcome of pregnancy after IVF treatment was associated with 2 parameters: higher levels of anti-Mullerian hormone as well as higher levels of magnesium in the pre-stimulation blood sample. These two parameters, however, showed no correlation. Spontaneous pregnancies as well as pregnancies after IVF show a fall of magnesium levels at 2-3 weeks of gestation. This drop of magnesium concentration is larger following IVF as compared to spontaneous pregnancies. Parallel to these changes TSH levels showed an increase in early IVF-pregnancy. At this time point we also observed a positive correlation between fT4 and TSH. This was not observed in spontaneous pregnancies. Thyroid antibodies showed no correlation to outcomes. CONCLUSIONS: In connection with the initiation of pregnancy following ovarian stimulation dynamic changes of magnesium and TSH levels can be observed. A positive correlation was found between fT4 and TSH in IVF pregnancies. In spontaneous pregnancies smaller increases of TSH levels are related to higher magnesium levels. GENERAL SIGNIFICANCE: We propose that magnesium plays a role in early pregnancy as well as in pregnancy success independently from anti-Mullerian hormone. Neither thyroid hormones nor thyroid antibodies were related to outcome. PMID- 26675755 TI - Empty Follicle Syndrome: The Possible Cause of Occurrence. AB - OBJECTIVES: Empty follicle syndrome (EFS), although rare, is a disappointing condition in which no oocytes are retrieved from mature follicle after ovulation induction in in vitro fertilization (IVF) cycles. The aim of this study was to estimate the incidence and factors associated with EFS. METHODS: All cycles resulting in EFS from May 2012 to September 2013 were retrospectively identified at a tertiary referral infertility center. Among the 3,356 cycles performed, 58 (1.7%) women who underwent their first IVF cycle and had no oocyte retrieval were enrolled in the study. Three different stimulation protocols (long, antagonist, and miniflare) were mainly used for induction of follicular growth. Data relating to the age, follicle stimulating hormone (FSH) level, anti-Mullerain hormone (AMH) level, and the number of ampules and follicles for each patient was obtained. RESULTS: Out of 58 individuals, 10 (17.2%) showed false type and 48 (82.8%) showed genuine EFS. The most frequent findings in our study were diminished ovarian reserve, low anti-Mullerian hormone (AMH; <=0.5 ng/mL), and less than four mature follicles, indicating EFS in 1.7% of the patients. CONCLUSION: Low serum AMH levels and a small number of follicles after ovarian stimulation is the manifestation of diminished ovarian reserve. Thus, we suggest that EFS could be a manifestation of low ovarian reserve. PMID- 26675756 TI - Answer to the question from page 469. PMID- 26675757 TI - HuR mediated post-transcriptional regulation as a new potential adjuvant therapeutic target in chemotherapy for pancreatic cancer. AB - AIM: To investigate the expression of HuR in pancreatic ductal adenocarcinoma (PDA) and to assess the effects of HuR silencing on the expression of cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) and the in vitro response to gemcitabine (GEM) treatment in pancreatic cell lines. METHODS: We compared the expression of HuR, COX-2, and HO-1 in PDA and normal pancreatic tissue using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. In addition, the HuR, COX-2 and HO-1 were analyzed in four types of cancer cell lines (MiaPaca2, Su.86.86, Capan-1, and Capan-2) with and without GEM treatment. Immunocytofluorescence analysis was used to investigate HuR localization in cells. Cell viability and response to GEM after HuR silencing were determined with the 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test and the crystal violet clonogenic assay, respectively. To measure apoptosis, activation of caspases 3/7 was evaluated using immunofluorescence. RESULTS: In PDA tissue obtained from patients not treated with GEM, HuR mRNA expression was 3.2 times lower (P < 0.05) and COX-2 and HO-1 mRNA expression was 2.3-fold and 7.2-fold higher (P < 0.05), respectively, than normal pancreatic tissue (from organ donor). qRT-PCR analysis showed that HuR, COX-2, and HO-1 mRNA were overexpressed in all cancer cell lines treated with the half maximal inhibitory concentration (IC50) dose of GEM compared with control cells (P < 0.05). Western blot analysis revealed that COX-2 and HO-1 levels were significantly decreased in cancer cells after HuR silencing. Furthermore, HuR silencing increased the response to GEM treatment and decreased cell viability by 11.6%-53.7% compared to control cell lines. Caspases 3 and 7 were activated after HuR silencing and GEM treatment in all pancreatic cancer cell lines. In comparison, treatment with GEM alone did not activate caspases 3 and 7 in the same cell lines. CONCLUSION: HuR mediated post-transcriptional upregulation of COX-2 and HO-1 expression after GEM treatment in pancreatic cancer cells. HuR silencing significantly increased the effectiveness of GEM treatment in vitro. PMID- 26675758 TI - Cerebral hemorrhage due to tuberculosis meningitis: a rare case report and literature review. AB - Tuberculosis (TB) is a common disease to threaten human health. TB of the central nervous system (CNS) is rare but the most serious type of systemic TB because of its high mortality rate, serious neurological complications and sequelae. In this case report, we describe a woman who presented with walking instability, intracerebral hemorrhage and leptomeningeal enhancement due to tuberculosis meningitis. The patient had no significant medical history and the initial clinical symptoms were walking instability. On analysis, the cerebrospinal fluid was colorless and transparent, the pressure was more than 400 mm H2O, there was lymphocytic pleocytosis, increased protein, and decreased glucose levels present. No tuberculosis or other bacteria were detected. The patient's brain computed tomography image showed intra-cerebral hemorrhage (ICH) and contrast magnetic resonance imaging showed ICH in the right frontal lob, and leptomeningeal enhancement. CNS TB is rare but has a high mortality rate. As this disease has no unique characteristics at first presentation such as epidemiology and obvious clinical manifestation, a diagnosis of CNS TB remains difficult. PMID- 26675760 TI - Extracellular vesicles in smoking-related lung diseases. PMID- 26675759 TI - Transpresentation of interleukin-15 by IL-15/IL-15Ralpha mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity. AB - In cancer immunotherapy, the use of dendritic cell (DC)-based vaccination strategies can improve overall survival, but until now durable clinical responses remain scarce. To date, DC vaccines are designed primarily to induce effective T cell responses, ignoring the antitumor activity potential of natural killer (NK) cells. Aiming to further improve current DC vaccination outcome, we engineered monocyte-derived DC to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Ralpha) using mRNA electroporation. The addition of IL-15Ralpha to the protocol, enabling IL-15 transpresentation to neighboring NK cells, resulted in significantly better NK-cell activation compared to IL-15 alone. Next to upregulation of NK-cell membrane activation markers, IL-15 transpresentation resulted in increased NK-cell secretion of IFN-gamma, granzyme B and perforin. Moreover, IL-15-transpresenting DC/NK cell cocultures from both healthy donors and acute myeloid leukemia (AML) patients in remission showed markedly enhanced cytotoxic activity against NK cell sensitive and resistant tumor cells. Blocking IL-15 transpresentation abrogated NK cell-mediated cytotoxicity against tumor cells, pointing to a pivotal role of IL-15 transpresentation by IL-15Ralpha to exert its NK cell-activating effects. In conclusion, we report an attractive approach to improve antitumoral NK-cell activity in DC-based vaccine strategies through the use of IL-15/IL-15Ralpha mRNA-engineered designer DC. PMID- 26675761 TI - Ketamine-mediated afferent-specific presynaptic transmission blocks in low threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats. AB - BACKGROUND: Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. METHODS: Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. RESULTS: Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ~50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 uM compared with the rest (708.2 uM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah types), rather than ketamine-less sensitive ones (A-types). CONCLUSIONS: These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway. PMID- 26675763 TI - Fish-oil supplementation: the controversy continues. PMID- 26675764 TI - Assessment of energy requirements in patients with short bowel syndrome by using the doubly labeled water method. AB - BACKGROUND: Short bowel syndrome (SBS) is a serious malabsorption disorder, and dietetic management of patients with SBS is extremely challenging. Once the degree of undernutrition has been assessed, successful dietary intervention is contingent on an accurate estimation and provision of energy needs. OBJECTIVE: We quantified total energy expenditure (TEE) in patients with SBS by using the doubly labeled water (DLW) method to inform energy needs and nutritional therapy goals. DESIGN: In this observational study, TEE was measured in 22 participants, 11 with SBS and 11 sex-, age-, and body mass index (BMI)-matched controls (non SBS), for 14 d with the DLW method. Predicted energy requirements were determined by using the Escott-Stump equation and compared with TEE determined with DLW. Resting energy expenditure was measured by using indirect calorimetry, and an accelerometer was also used to determine physical activity level. RESULTS: Participants were aged (mean +/- SD) 53 +/- 8 y. Measured TEE was significantly higher than predicted TEE for the SBS group (1875 +/- 276 compared with 1517 +/- 175 kcal/d, P = 0.001) and also for the non-SBS group (2393 +/- 445 compared with 1532 +/- 178 kcal/d, P < 0.01). Measured TEE was significantly lower in the SBS group than in the non-SBS group (P < 0.01); however, predicted TEE did not differ significantly between the groups (P = 0.84). No significant differences were seen between measured and predicted resting energy expenditure either within or between groups. CONCLUSIONS: Measured TEE in patients with SBS was significantly higher than predicted by using standard equations but also lower than values for age-, BMI-, and sex-matched non-SBS controls. Currently used formulas in clinical practice appear to underestimate energy requirements of patients with SBS, and revision is needed to prevent underfeeding and improve long-term prognosis. This trial was registered at clinicaltrials.gov as NCT02113228. PMID- 26675762 TI - Pathophysiology of anorexia in the cancer cachexia syndrome. AB - Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID- 26675766 TI - Best (but oft-forgotten) practices: sensitivity analyses in randomized controlled trials. AB - A randomized controlled clinical trial is the best way to minimize bias in ascertaining treatment effects, but the credibility of the results of a trial depends on the validity of the methods used to analyze the data, and the conditions under which such methods produce valid answers. A sensitivity analysis is a method to determine the robustness of trial findings by examining the extent to which results are affected by changes in methods, models, values of unmeasured variables, or assumptions. The goal of a sensitivity analysis is to identify results that are most dependent on questionable or unsupported assumptions. In this article, we briefly review the current use of sensitivity analyses in a random sample of published nutrition literature and provide a guide on the use of sensitivity analyses in randomized trials as to when to consider them, what to consider when planning them, and different methods of implementing them. We propose an 8-step strategy for improving the approach to conducting and reporting sensitivity analyses in nutrition-based trials. PMID- 26675765 TI - Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women. AB - BACKGROUND: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]. OBJECTIVE: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 MUg/d. DESIGN: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation. RESULTS: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained <=2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579. CONCLUSIONS: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591. PMID- 26675767 TI - Appetitive traits and food intake patterns in early life. AB - BACKGROUND: High food responsiveness (FR) and low satiety responsiveness (SR) are 2 appetitive traits that have been associated longitudinally with risk of excessive weight gain; however, to our knowledge, no studies have examined the associations between these traits and eating patterns in daily life in young children. OBJECTIVE: We tested the hypothesis that higher FR is independently associated with a higher meal frequency and that lower SR is associated with a larger meal size. DESIGN: Data were from 1102 families (2203 children) from the Gemini twin birth cohort. Appetite was assessed with the use of the Child Eating Behavior Questionnaire when the children were 16 mo old (mean +/- SD: 15.73 +/- 1.08 mo old), and meal frequency (eating occasions per day) and meal size (kilojoules per eating occasion) were determined from 3-d diet diaries completed by parents when the children were 21 mo old (mean +/- SD: 20.65 +/- 1.10 mo old). Complex samples general linear models were used to explore cross-sectional associations between appetitive traits and meal variables. RESULTS: After adjustment for the covariates gestational age, birth weight, sex, difference in age at diet-diary completion, and appetite measurement, higher FR was associated with more-frequent meals (B +/- SE: 0.13 +/- 0.04; P = 0.001) but not with meal size (P = 0.41), and lower SR was associated with a larger meal size (B +/- SE: 47.61 +/- 8.79; P < 0.001) but not with meal frequency (P = 0.15). CONCLUSIONS: FR and SR predict different eating variables with more food-responsive children eating more frequently, whereas less-satiety-responsive children eat more food on each eating occasion. Different strategies may be required to reduce the potential effects of FR and SR on weight gain. PMID- 26675769 TI - Reflections on nutritional cancer epidemiology. PMID- 26675768 TI - Biofortified yellow cassava and vitamin A status of Kenyan children: a randomized controlled trial. AB - BACKGROUND: Whereas conventional white cassava roots are devoid of provitamin A, biofortified yellow varieties are naturally rich in beta-carotene, the primary provitamin A carotenoid. OBJECTIVE: We assessed the effect of consuming yellow cassava on serum retinol concentration in Kenyan schoolchildren with marginal vitamin A status. DESIGN: We randomly allocated 342 children aged 5-13 y to receive daily, 6 d/wk, for 18.5 wk 1) white cassava and placebo supplement (control group), 2) provitamin A-rich cassava (mean content: 1460 MUg beta carotene/d) and placebo supplement (yellow cassava group), and 3) white cassava and beta-carotene supplement (1053 MUg/d; beta-carotene supplement group). The primary outcome was serum retinol concentration; prespecified secondary outcomes were hemoglobin concentration and serum concentrations of beta-carotene, retinol binding protein, and prealbumin. Groups were compared by using ANCOVA, adjusting for inflammation, baseline serum concentrations of retinol and beta-carotene, and stratified design. RESULTS: The baseline prevalence of serum retinol concentration <0.7 MUmol/L and inflammation was 27% and 24%, respectively. For children in the control, yellow cassava, and beta-carotene supplement groups, the mean daily intake of cassava was 378, 371, and 378 g, respectively, and the total daily supply of provitamin A and vitamin A from diet and supplements was equivalent to 22, 220, and 175 MUg retinol, respectively. Both yellow cassava and beta-carotene supplementation increased serum retinol concentration by 0.04 MUmol/L (95% CI: 0.00, 0.07 MUmol/L); correspondingly, serum beta-carotene concentration increased by 524% (448%, 608%) and 166% (134%, 202%). We found no effect on hemoglobin concentration or serum concentrations of retinol-binding protein and prealbumin. CONCLUSIONS: In our study population, consumption of yellow cassava led to modest gains in serum retinol concentration and a large increase in beta-carotene concentration. It can be an efficacious, new approach to improve vitamin A status. This study was registered with clinicaltrials.gov as NCT01614483. PMID- 26675770 TI - Omega-3 long-chain PUFA intake during pregnancy and allergic disease outcomes in the offspring: a systematic review and meta-analysis of observational studies and randomized controlled trials. AB - BACKGROUND: There is some evidence that increased maternal intake of omega-3 (n 3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may reduce the incidence of immunoglobulin E (IgE)-mediated allergic disease. OBJECTIVE: We aimed to evaluate prenatal n-3 LC-PUFA dietary exposure in observational studies and n-3 LC-PUFA supplementation in randomized controlled trials (RCTs) on outcomes of IgE-mediated allergic disease. DESIGN: We conducted searches of the Cochrane Central Register of Controlled Trials, PubMed, Ovid MEDLINE, EMBASE, CINAHL, SCOPUS, and Web of Science to 30 July 2015. We included prospective cohort studies that showed an association between maternal fish or n-3 LC-PUFA intake during pregnancy and RCTs with a prenatal intervention to modify maternal n-3 LC-PUFA intake and outcomes of allergic disease (eczema, rhino conjunctivitis, asthma) or sensitization in the offspring. RESULTS: A total of 13 publications from 10 prospective cohort studies and 7 publications representing 5 unique RCTs were included. Three RCTs were combined in a meta-analysis for selected outcomes. Nine of 13 observational study publications and 5 of 7 publications from RCTs found a protective association between increased prenatal n-3 LC-PUFA or fish intake and incidence of allergic disease symptoms in the child. Meta-analysis was limited because of the heterogeneity of the RCTs. Pooled results showed a significant reduction in the incidence of "atopic eczema," "any positive SPT [skin-prick test]," "sensitization to egg," and "sensitization to any food" in the first 12 mo of life [RRs (95% CIs): 0.53 (0.35, 0.81), P = 0.004; 0.68 (0.52-0.89), P = 0.006; 0.55 (0.39-0.76), P = 0.0004; and 0.59 (0.46, 0.76), P < 0.0001, respectively]. CONCLUSIONS: Our systematic review and meta analysis was suggestive of benefits of increased n-3 LC-PUFAs in the maternal diet and outcomes of childhood allergic disease. However, due to the inconsistency in results, the hypothesis linking maternal n-3 LC-PUFA intake to childhood allergic disease cannot unequivocally be confirmed or rejected. PMID- 26675772 TI - Dietary vitamin D dose-response in healthy children 2 to 8 y of age: a 12-wk randomized controlled trial using fortified foods. AB - BACKGROUND: Vitamin D is fundamental for bone health. A high proportion of Canadian 2- to 8-y-olds do not meet the Estimated Average Requirement (EAR) of 400 IU/d. OBJECTIVE: The objective was to determine whether vitamin D intakes consistent with the EAR or Recommended Dietary Allowance (RDA), through fortification of additional dairy products, would result in higher vitamin D status in young children. DESIGN: Participants aged 2-8 y (n = 77; Montreal, Canada) were randomly assigned to 1 of 3 dietary vitamin D targets (control; EAR: 400 IU/d; or RDA: 600 IU/d) for 12 wk (January to April 2014). Anthropometric measurements, demographic characteristics, dietary intakes, fasting serum parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], and ionized calcium were compared by using mixed-model ANOVA. RESULTS: Participants' mean +/- SD age was 5.1 +/- 1.9 y; 54.5% were boys with body mass index z scores of 0.50 +/- 0.85. Compliance was 85% overall. No differences were observed in baseline dietary vitamin D intakes or serum 25(OH)D. At 12 wk, the EAR and RDA groups had significantly higher vitamin D intakes [median (IQR): control, 227 (184-305) IU/d; EAR, 410 (363-516) IU/d; and RDA, 554 (493-653) IU/d; P < 0.05] and serum 25(OH)D concentrations (control: 55.8 +/- 12.3 nmol/L; EAR: 64.1 +/- 10.0 nmol/L; and RDA: 63.7 +/- 12.4 nmol/L; P < 0.05) than the control group. Ninety-six percent of children in the EAR and RDA groups and 67% of the control group had 25(OH)D concentrations >=50 nmol/L. CONCLUSION: Increasing the vitamin D intakes of young children through fortification of alternative dairy products results in significantly higher serum concentrations of 25(OH)D and a significantly greater proportion of children with serum 25(OH)D >=50 nmol/L during periods of minimal ultraviolet B radiation exposure. This trial was registered at clinicaltrials.gov as NCT02097160 and had Health Canada Temporary Marketing Authorization Letters for both products (TM-13-0432 and TM-13-0433). PMID- 26675773 TI - Macronutrient composition and gestational weight gain: a systematic review. AB - BACKGROUND: Abnormal gestational weight gain is associated with unfavorable pregnancy outcomes. Several risk factors have been identified, but the effect of macronutrient intake during pregnancy on gestational weight gain has not been systematically evaluated in both high-income countries and low- and middle-income countries. OBJECTIVE: We conducted a systematic review of the literature in 8 different databases (until 12 August 2015) to assess whether energy intake and macronutrient intake (i.e., protein, fat, and carbohydrate) during pregnancy were associated with gestational weight gain (following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). RESULTS: Of 7623 identified references, we included 56 articles (46 observational studies and 10 trials, 28 of which were in high-income countries and 28 of which were in low- and middle income countries). Eleven of the included articles were of high quality (20%). Results of 5 intervention and 7 high-quality observational studies suggested that higher energy intake during pregnancy is associated with higher gestational weight gain (n = 52). Results from observational studies were inconsistent for protein intake (n = 29) and carbohydrate intake (n = 18). Maternal fat intake (n = 25) might be associated with gestational weight gain as suggested by observational studies, although the direction of this association might depend on specific types of fat (e.g., saturated fat). Macronutrient intake was not consistently associated with the prevalence of inadequate or excessive gestational weight gain. Associations were comparable for high-income countries and low- and middle-income countries. CONCLUSIONS: The current literature provides evidence that energy intake is associated with gestational weight gain, but the roles of individual macronutrients are inconsistent. However, there is a need for higher-quality research because the majority of these studies were of low quality. PMID- 26675771 TI - Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men. AB - BACKGROUND: Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic L-carnitine feeding on a daily basis in a high carbohydrate beverage. OBJECTIVE: We investigated whether whey protein ingestion could reduce the carbohydrate load required to stimulate insulin-mediated muscle carnitine accretion. DESIGN: Seven healthy men [mean +/- SD age: 24 +/- 5 y; body mass index (in kg/m(2)): 23 +/- 3] ingested 80 g carbohydrate, 40 g carbohydrate + 40 g protein, or control (flavored water) beverages 60 min after the ingestion of 4.5 g L-carnitine tartrate (3 g L-carnitine; 0.1% (2)[H]3-L-carnitine). Serum insulin concentration, net forearm carnitine balance (NCB; arterialized-venous and venous plasma carnitine difference * brachial artery flow), and carnitine disappearance (Rd) and appearance (Ra) rates were determined at 20-min intervals for 180 min. RESULTS: Serum insulin and plasma flow areas under the curve (AUCs) were similarly elevated by carbohydrate [4.5 +/- 0.8 U/L . min (P < 0.01) and 0.5 +/- 0.6 L (P < 0.05), respectively] and carbohydrate+protein [3.8 +/- 0.6 U/L . min (P < 0.01) and 0.4 +/- 0.6 L (P = 0.05), respectively] consumption, respectively, compared with the control visit (0.04 +/- 0.1 U/L . min and -0.5 +/ 0.2 L). Plasma carnitine AUC was greater after carbohydrate+protein consumption (3.5 +/- 0.5 mmol/L . min) than after control and carbohydrate visits [2.1 +/- 0.2 mmol/L . min (P < 0.05) and 1.9 +/- 0.3 mmol/L . min (P < 0.01), respectively]. NCB AUC with carbohydrate (4.1 +/- 3.1 MUmol) was greater than during control and carbohydrate-protein visits (-8.6 +/- 3.0 and -14.6 +/- 6.4 MUmol, respectively; P < 0.05), as was Rd AUC after carbohydrate (35.7 +/- 25.2 MUmol) compared with control and carbohydrate consumption [19.7 +/- 15.5 MUmol (P = 0.07) and 14.8 +/- 9.6 MUmol (P < 0.05), respectively]. CONCLUSIONS: The insulin-mediated increase in forearm carnitine balance with carbohydrate consumption was acutely blunted by a carbohydrate+protein beverage, which suggests that carbohydrate+protein could inhibit chronic muscle carnitine accumulation. PMID- 26675775 TI - Energy and macronutrient intake after gastric bypass for morbid obesity: a 3-y observational study focused on protein consumption. AB - BACKGROUND: The effect of a Roux-en-Y gastric bypass (RYGB) on body weight has been amply documented, but few studies have simultaneously assessed the evolution of energy and macronutrient intakes, energy expenditure, and changes in body composition over time after an RYGB. OBJECTIVE: We evaluated energy and macronutrient intakes, body composition, and the basal metabolic rate (BMR) in obese female patients during the initial 3 y after an RYGB. METHODS: Sixteen women with a mean +/- SEM body mass index (in kg/m(2)) of 44.1 +/- 1.6 were included in this prospective observational study. The women were studied on 6 different occasions as follows: before and 1, 3, 6, 12 (n = 16), and 36 (n = 8) mo after surgery. On each occasion, food intake was evaluated from 4- or 7-d dietary records, body composition was assessed with the use of bio impedancemetry, and energy expenditure was measured with the use of indirect calorimetry. RESULTS: Body weight evolution showed the typical pattern reported after an RYGB. Total energy intake was 2072 +/- 108 kcal/d at baseline and decreased to 681 +/- 58 kcal/d at 1 mo after surgery (P < 0.05 compared with at baseline). Total energy intake progressively increased to reach 1240 +/- 87 kcal/d at 12 mo after surgery (P < 0.05 compared with at 1 mo after surgery) and 1448 +/- 57 kcal/d at 36 mo after surgery (P < 0.05 compared with at 12 mo after surgery). Protein intake was 87 +/- 4 g/d at baseline and +/- 2 g/d 1 mo after surgery (P < 0.05 compared with at baseline) and increased progressively thereafter to reach 57 +/- 3 g/d at 36 mo after surgery (P < 0.05 compared with at 1 mo after surgery). Carbohydrate and fat intakes over time showed similar patterns. Protein intake from meat and cheese were significantly reduced early at 1 mo after surgery but increased thereafter (P < 0.05). The BMR decreased from 1.12 +/- 0.04 kcal/min at baseline to 0.93 +/- 0.03, 0.86 +/- 0.03, and 0.85 +/- 0.04 kcal/min at 3, 12, and 36 mo after surgery, respectively (all P < 0.05 compared with at baseline). CONCLUSIONS: Total energy, carbohydrate, fat, and protein intakes decreased markedly during the initial 1-3 mo after an RYGB, whereas the BMR moderately decreased. The reduction in protein intake was particularly severe at 1 mo after surgery, and protein intake increased gradually after 3-6 mo after surgery. This trial was registered at clinicaltrials.gov as NCT01891591. PMID- 26675776 TI - Acute effect of red meat and dairy on glucose and insulin: a randomized crossover study. AB - BACKGROUND: In contrast with some epidemiologic evidence, our previous research showed that a 4-wk diet that was high in low-fat dairy reduced insulin sensitivity compared with the effect of a diet that was high in red meat. OBJECTIVE: We investigated whether a dairy meal would produce a greater insulin response than a carbohydrate-matched red meat meal would, which might account for the change in insulin sensitivity. DESIGN: One meal contained lean red meat, bread, and orange juice, and the other meal contained skim milk, low-fat yogurt, cheese, and bread. Meals were isoenergetic, equal in macronutrient profile, and consumed 1 wk apart. Glucose, insulin, and triglycerides were measured before and 30, 60, 90, 120, 150, and 180 min after meal consumption. Differences between meals were tested with the use of a repeated-measures ANOVA and paired sample t tests. RESULTS: Nineteen men and 24 women [mean +/- SD age: 50.8 +/- 16.0 y; body mass index (in kg/m(2)): 30.0 +/- 3.5] completed the study. Twenty-two participants had normal glucose tolerance, and 21 participants had impaired fasting glucose or impaired glucose tolerance. The red meat meal resulted in a higher glucose response at 30 min after consumption (P < 0.001); however, the glucose total AUC was not different between meals (P = NS). The mean +/- SEM incremental AUC (iAUC) for glucose was significantly higher after the dairy meal than after the red meat meal (2.23 +/- 0.49 compared with 0.88 +/- 0.57 mmol/L . 3 h, respectively; P = 0.004). The insulin total AUC and iAUC were not different between meals (iAUC: 159.65 +/- 20.0 mU/L . 3 h for red meat compared with 167.49 +/- 24.1 mU/L . 3 h for dairy; P = NS). CONCLUSIONS: Lean red meat and low-fat dairy produced a similar glycemic response. The higher glucose response 30 min after consumption of the red meat meal was likely attributable to differences in the glycemic load between orange juice and milk and yogurt. An insulinotropic effect of dairy was not observed. This trial was registered at www.anzctr.org.au as ACTRN12615000164594. PMID- 26675774 TI - Is there a causal role for homocysteine concentration in blood pressure? A Mendelian randomization study. AB - BACKGROUND: An understanding of whether homocysteine is a cause or a marker of increased blood pressure is relevant because blood homocysteine can be effectively lowered by safe and inexpensive interventions (e.g., vitamin B-6, B 9, and B-12 supplementation). OBJECTIVE: The aim was to assess the causal influence of homocysteine on systolic and diastolic blood pressure (SBP and DBP, respectively) in adults with the use of Mendelian randomization (MR). DESIGN: Data from the 1982 Pelotas Birth Cohort (Brazil) were used. A total of 4297 subjects were evaluated in 2004-2005 (mean age: 22.8 y). The association of homocysteine concentration with SBP and DBP was assessed by conventional ordinary least-squares (OLS) linear regression and 2-stage least-squares (2SLS) regression (MR analysis). The single nucleotide polymorphism (SNP) methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) was used as proxy for homocysteine concentration. We also applied MR to data from the International Consortium for Blood Pressure (ICBP) genomewide association studies (>69,000 participants) using rs1801133 and additional homocysteine-associated SNPs as instruments. RESULTS: In OLS regression, a 1-SD unit increase in log homocysteine concentration was associated with an increase of 0.9 (95% CI: 0.4, 1.4) mm Hg in SBP and of 1.0 (95% CI: 0.6, 1.4) mm Hg in DBP. In 2SLS regression, for the same increase in homocysteine, the coefficients were -1.8 mm Hg for SBP (95% CI: -3.9, 0.4 mm Hg; P = 0.01) and 0.1 mm Hg for DBP (95% CI: -1.5, 1.7 mm Hg; P = 0.24). In the MR analysis of ICBP data, homocysteine concentration was not associated with SBP (beta = 0.6 mm Hg for each 1-SD unit increase in log homocysteine; 95% CI: -0.8, 1.9 mm Hg) but was positively associated with DBP (beta = 1.1 mm Hg; 95% CI: 0.2, 1.9 mm Hg). The association of genetically increased homocysteine with DBP was not consistent across different SNPs. CONCLUSION: Overall, the present findings do not corroborate the hypothesis that homocysteine has a causal role in blood pressure, especially in SBP. PMID- 26675777 TI - Leukocyte telomere length is related to appendicular lean mass: cross-sectional data from the Berlin Aging Study II (BASE-II). AB - BACKGROUND: Age-related progressive loss of muscle mass is an increasing problem in our aging society, affecting physical ability, risk of falls, and need for health care. Telomere length has been recognized as a marker of biological age on the population level. The relation between muscle mass in advanced age and telomere length, however, has rarely been examined. OBJECTIVE: We evaluated the relation between appendicular lean mass (ALM) and relative leukocyte telomere length (rLTL) in 1398 participants of the Berlin Aging Study II (mean +/- SD age: 68.2 +/- 3.7 y; 49.6% men). DESIGN: rLTL was determined by real-time polymerase chain reaction. Lean mass was estimated by dual X-ray absorptiometry and examined as leg lean mass (LLM), ALM, and the ratio of ALM to body mass index (ALMBMI). RESULTS: Weak, but highly significant (P < 0.001), correlations of rLTL with ALM (r = 0.248), ALMBMI (r = 0.254), and LLM (r = 0.263) were found. In the fully adjusted model that included age, BMI, low-grade inflammation, lifestyle factors, and morbidities as potential confounders, rLTL was associated with ALM (beta = 1.11, SEM = 0.46, P = 0.017), LLM (beta = 1.20, SEM = 0.36, P = 0.001), and ALMBMI (beta = 0.04, SEM = 0.02, P = 0.013) in men and with LLM in women (beta = 0.78, SEM = 0.35, P = 0.026). CONCLUSIONS: Our results suggest that short telomeres may be a risk factor for lower ALM, particularly for low LLM. To confirm the association between telomere attrition and loss of LLM and ALMBMI, which are highly relevant for physical ability, further research in a longitudinal context is needed. The medical portion of this trial was registered in the German Clinical Trials Registry (http://drks-neu.uniklinik freiburg.de/drks_web/navigate.do?navigationId=start) as DRKS00009277. PMID- 26675778 TI - Astaxanthin has no effect on arterial stiffness, oxidative stress, or inflammation in renal transplant recipients: a randomized controlled trial (the XANTHIN trial). AB - BACKGROUND: There is evidence that renal transplant recipients have accelerated atherosclerosis that is manifest by increased cardiovascular morbidity and mortality. The high incidence of atherosclerosis is, in part, related to increased arterial stiffness, vascular dysfunction, elevated oxidative stress, and inflammation associated with immunosuppressive therapy. The carotenoid astaxanthin has shown potent antioxidant and anti-inflammatory properties. OBJECTIVE: The aim was to investigate the effects of oral astaxanthin on arterial stiffness, oxidative stress, and inflammation in renal transplant recipients. DESIGN: This trial used a randomized, placebo-controlled, double-blind design in which 61 patients received either 12 mg astaxanthin/d or an identical placebo orally for 1 y. Primary outcomes were 1) arterial stiffness measured by aortic pulse wave velocity (PWV), 2) oxidative stress assessed by total plasma F2 isoprostanes, and 3) inflammation assessed by plasma pentraxin-3. Secondary outcomes included vascular function, carotid artery intima-media thickness, augmentation index, central blood pressure, subendocardial viability ratio, and additional measures of oxidative stress and inflammation. Patients underwent assessments at baseline and at 6 and 12 mo. RESULTS: Fifty-eight participants completed the study. There were no significant between-group differences in the changes in any of the primary outcome measures (PWV changed by +9.5% and +6.0%, F2-isoprostanes changed by -3.0% and -9.7%, and pentraxin-3 changed by +50.6% and -11.0% in the placebo and astaxanthin groups, respectively). There were no significant between-group differences in secondary outcome measures. Larger-than expected variability decreased the power of the study and increased the possibility of a type 2 statistical error. CONCLUSION: Astaxanthin (12 mg/d for 12 mo) had no effect on arterial stiffness, oxidative stress, or inflammation in renal transplant recipients. This trial was registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12608000159358. PMID- 26675779 TI - Vitamin D content in human breast milk: a 9-mo follow-up study. AB - BACKGROUND: Parents are advised to avoid the direct sun exposure of their newborns. Therefore, the vitamin D status of exclusively breastfed newborns is entirely dependent on the supply of vitamin D from breast milk. OBJECTIVES: We explored concentrations of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH)D correlated significantly and were higher in hindmilk than in foremilk. Milk concentrations were also correlated with maternal plasma 25(OH)D concentrations. In foremilk and hindmilk, concentrations were a median (IQR) of 1.35% (1.04-1.84%) and 2.10% (1.63-2.65%), respectively, of maternal plasma 25(OH)D concentrations (P < 0.01). Milk concentrations showed a significant seasonal variation. Mothers who were taking vitamin D supplements had higher concentrations than did nonusers. Medians (IQRs) of infant daily intake through breast milk of vitamin D and 25(OH)D were 0.10 MUg (0.02-0.40 MUg) and 0.34 MUg (0.24-0.47 MUg), respectively, which were equal to a median (IQR) antirachitic activity of 77 IU/d (52-110 IU/d). CONCLUSIONS: The supply of vitamin D from breast milk is limited. Exclusively breastfed infants received <20% of the daily dose recommended by the Institute of Medicine for infants during the first year of life. This trial was registered at clinicaltrials.gov as NCT02548520. PMID- 26675780 TI - Polycomb in Transcriptional Phase Transition of Developmental Genes. AB - Combinatorial associations between distinct chromatin domains, namely promoters and cis-regulatory elements, determine transcriptional status. Developmental regulatory gene expression, mostly regulated by the Polycomb/Trithorax group of chromatin regulators, is often temporally and spatially specific, and sometimes changes repeatedly within the same cell lineage. Dysregulated expression of these genes causes morphological and/or functional disorganization of tissues and organs. Therefore, maintenance of both the active and negative states of transcription is equally important. In this review, we summarize the mechanisms of transition between transcriptional status of developmental regulators, including complex processes for enhancer activation and promoter-enhancer association. In particular, we propose testable models in which Polycomb group factors contribute to promoter-enhancer associations and thus proper gene expression. PMID- 26675781 TI - Totally anomalous pulmonary venous drainage - supracardiac type: ultrasound assessment of anatomically determined stenosis of the vertical vein collecting pulmonary venous return. AB - The diagnosis of the congenital heart defects, among others totally anomalous pulmonary venous drainage, is based on echocardiography. While the visualization of intracardiac structures rarely causes significant difficulties, the vessels positioned outside the heart, e.g. the pulmonary veins, are often hidden behind tissues impermeable to ultrasounds, which may necessitate the use of other imaging methods, such as computer tomography, nuclear magnetic resonance or angiocardiography. The serious limitation of these techniques, especially in pediatric age, is the necessity to administer general anesthesia and contrast media. In order to obtain clear images, the appropriate concentration of a contrast agent in the vessels is necessary, which is not always possible in a patient with severe circulatory failure. Therefore, every effort should be made to obtain as much information necessary for treatment determination as possible from echocardiography, in spite of its limitations. A significant morphological factor of totally anomalous pulmonary venous drainage is the connection between the pulmonary and systemic veins, which in the supracardiac type is the vertical vein draining into the left brachiocephalic vein. The narrowing of this connection impedes the return of the blood from the lungs, which leads to the secondary edema and severe, abrupt cardiorespiratory insufficiency. Such a narrowing should be sought for in every case of totally anomalous pulmonary venous drainage since it constitutes an indication for an urgent surgery. On the basis of own experience and information obtained from the pertinent literature, the authors describe the rules and criteria of the diagnosis of this rare supracardiac form of the heart defect with the presence of the vertical vein which may undergo stenosis due to a phenomenon called the anatomical or bronchoarterial vise. It is formed when the vessel "pushes through" a narrow opening bordered by the left pulmonary artery from the inferior side as well as the left main bronchus and the arterial duct or ligament from the superior side. This article describes a technique of echocardiographic test enabling the precise visualization of the vessel's course and the differentiation from a more common variant of the defect - without external stenosis. PMID- 26675782 TI - Comment on "A Comprehensive Analysis of Groundwater Quality in The Barnett Shale Region". PMID- 26675785 TI - [Application of neurophysiological monitoring]. PMID- 26675784 TI - Impact of the mass media OBERTAMENT campaign on the levels of stigma among the population of Catalonia, Spain. AB - Reducing public stigma could improve patients' access to care, recovery and social integration. The aim of the study was to evaluate a mass media intervention, which aimed to reduce the mental health, related stigma among the general population in Catalonia (Spain). We conducted a cross-sectional population-based survey of a representative sample of the Catalan non institutionalized adult population (n=1019). We assessed campaign awareness, attitudes to people with mental illness (CAMI) and intended behaviour (RIBS). To evaluate the association between campaign awareness and stigma, multivariable regression models were used. Over 20% of respondents recognized the campaign when prompted, and 11% when unprompted. Campaign aware individuals had better attitudes on the benevolence subscale of the CAMI than unaware individuals (P=0.009). No significant differences in authoritarianism and support for community mental health care attitudes subscales were observed. The campaign aware group had better intended behaviour than the unaware group (P<0.01). The OBERTAMENT anti-stigma campaign had a positive impact to improve the attitudes and intended behaviour towards people with mental illness of the Catalan population. The impact on stigma was limited to attitudes related to benevolence. A wider range of anti-stigma messages could produce a stronger impact on attitudes and intended behaviour. PMID- 26675783 TI - Assessment of Liver Function Using (99m)Tc-Mebrofenin Hepatobiliary Scintigraphy in ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy). AB - ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new surgical technique for patients in whom conventional treatment is not feasible due to insufficient future remnant liver (FRL). During the first stage of ALPPS, accelerated hypertrophy of the FRL is induced by ligation of the portal vein and in situ split of the liver. In the second stage, the deportalized liver is removed when the FRL volume has reached >=25% of total liver volume. However, FRL volume does not necessarily reflect FRL function. (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) with SPECT-CT is a quantitative test enabling regional assessment of parenchymal uptake function using a validated cut-off value for the prediction of postoperative liver failure (2.7%/min/m(2)). This paper describes the changes in FRL function and FRL volume in a 79-year-old patient diagnosed with metachronous colonic liver metastases who underwent ALPPS. We have observed a substantial difference between the increase in FRL volume and FRL function suggesting that HBS with SPECT-CT enables monitoring of the FRL function and could be a useful tool in the timing of resection in the second stage of the ALPPS procedure. PMID- 26675786 TI - [Application of neurophysiological monitoring in the surgical treatment of cerebral vascualr diseases]. PMID- 26675787 TI - [Intraoperative neurophysiological monitoring during aortic surgery: history, current situation and future development trends]. PMID- 26675788 TI - [Neurophysiological monitoring in spinal deformity surgery]. PMID- 26675789 TI - [Brain function-the next breakthrough of organ bedside monitoring]. PMID- 26675790 TI - [Study status and prospect of intraoperative neurophysiological monitoring]. PMID- 26675791 TI - [Preliminary study of facial nerve F wave evaluation hypoglossal-facial nerve reconstruction with predegenerated nerve graft for peripheral facial palsy]. AB - OBJECTIVE: To Preliminary study of facial nerve F wave evaluation hypoglossal facial nerve reconstruction with pre-degenerated nerve graft for peripheral facial palsy. METHODS: The clinical data were retrospectively reviewed for 30 patients with peripheral facial palsy after cerebellontine angle underwent nerve anastomosis were analyzed between November 2011 and February 2014. F wave and M wave detection were used to evaluate the pre-, post-opertive and status.The hypoglossal-facial nerve by "side- to-side" anastomisis was performed. RESULTS: All patients were followed-up.The mean time of follow-up was 8 months (ranged from 3 to 20 months). 12 patients were found a higher recovery of facial nerve function after the nerve anastomosis.16 patients who F wave of post-opertive were found a higher recovery compared to F wave of pre-opertive (P < 0.05). CONCLUSION: The hypoglossal-facial nerve by "side"-to-side anastomisis with pre degenerated auto-nerve graft was effective for the treatment of peripheral facial palsy after CPA tumor resection, F wave can be used as one of the objective index for the effect of the operation. PMID- 26675792 TI - [Alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression for primary trigeminal neuralgia]. AB - OBJECTIVE: To explore the alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression (MVD) for primary trigeminal neuralgia. METHODS: In 2014, a total of 44 patients with an initial diagnosis of primary trigeminal neuralgia were consecutively recruited for surgery. And 41 of them with an intraoperative confirmation of primary trigeminal neuralgia underwent MVD. Intraoperative neuroelectrophysiological monitoring was employed for brainstem auditory evoked potentials (BAEPs), spontaneous electromyogram for obicularis oculi, obicularisoris and masseter muscles. The real-time alarming report was offered to the operator who adjusted operations accordingly. RESULTS: There were abnormal changes in 23 cases (56.10%) with a total of 77 instances (BAEPs 27, trigeminal nerve 32, facial nerve 18). The outcomes were no facial pain (n=26), pain relief (n=15) and facial numbness (n=6, two with concurrent hearing disturbance). And the rates of facial pain disappearance and sequela occurrence were much better than those in controls without monitoring. CONCLUSION: Intraoperative neuroelectrophysiological monitoring helps enhance the MVD effect and decrease operative squela through alarming reporting. PMID- 26675793 TI - [Baseline and alert level of somatosensory evoked potential monitoring in scoliosis surgery]. AB - OBJECTIVE: To explore the choice of timing for baseline and alert levels of somatosensory evoked potential (SEP) monitoring during scoliosis surgery. METHODS: From March 2011 to December 2014, a total of 113 patients with kyphoscoliosis deformity were monitored intraoperatively by SEP. There were 52 males and 61 females with a mean age of (20 +/- 15) years. All the patients were recorded preoperativeandintraoperative SEPs on double lower limbs. Latency and amplitude of SEPs were recorded after anesthesia and vertebral laminae exposure respectively and compared with each other. Intraoperative SEPs were compared to baseline as SEP after exposure and divided into 4 groups of A (<40%), B (40% 50%), C (50%-60%) and D (>60%) according to the reduced amplitude. Nerve functions were recorded during follow-ups. RESULTS: Significant statistical difference existed between SEPs post-anesthesia and SEPs after vertebral laminae exposure (P < 0.01). Compared with SEP post-anesthesia, the latency of SEP after exposure was prolonged with (3.28 +/- 1.72) ms (left lower limb) and (3.30 +/- 2.09) ms (right lower limb) and amplitude decreased with 0.17(0.39) uV (left lower limb) and 0.19(0.40) uV (right lower limb). There was a positive relationship of impaired nerve function between groups C and D (P < 0.05). CONCLUSION: Adopting SEP waveform after exposure as a baseline can improve the accuracy of SEP monitoring during scoliosis surgery. Intraoperative alarm with a reduced amplitude over 50% as the standard may be too sensitive. Alert with a reduced amplitude of over 60% reduces the false positive rate of alarm. PMID- 26675794 TI - [Intraoperative neurophysiological monitoring in children undergoing tethered cord surgery]. AB - OBJECTIVE: To retrospectively explore the multimodal intraoperative monitoring (IOM) technique during untethering cord procedures in 37 patients between 1 month and 16 years of age with tethered cord syndrome during 2014. METHODS: All patients were diagnosed as tethered cord syndrome by clinical manifestations and verified by magnetic resonance imaging (MRI). Free and trigger electromyogram (EMG) and transcranial motor-evoked potentials (tcMEP) of extremity muscles and anal sphincters were used to map the nerves and monitor the functional motor integrity continuously. RESULTS: The monitorability rate was 100 % for nervous mapping, 86.5% (32/37) for extremity muscle tcMEP. In all patients, tcMEP remained stable during surgery, 43.8% (14/32) patients showed a significant postoperative increase of amplitude of tcMEP, none of them patients presented a significant and yet transient neurological worsening. CONCLUSION: The combined technique of monitoring and mapping may boost the procedural safety, minimize the long-term morbidity and improve the clinical outcomes. PMID- 26675795 TI - [Application of continuous video-electroencephalographic monitoring in patients with consciousness disorders in intensive care unit]. AB - OBJECTIVE: To evaluate the application value of continuous video electroencephalographic (cVEEG) monitoring in patients with consciousness disorders in intensive care unit (ICU). METHODS: Retrospective analyses were conducted for applying cVEEG in the clinical diagnosis and outcome evaluation of 54 patients with consciousness disorders in intensive care unit (ICU) at our hospital from January 2008 to April 2014. RESULTS: The most common cause was cerebrovascular disease (46.3%) followed by ischemic-hypoxic encephalopathy after cadio-pulmonary resuscitation (18.5%). And 49 cases (90.7%) showed an abnormal background on initial cVEEG, 19 cases (35.2%) had epileptic discharge and 8 cases (14.8%) were diagnosed with nonconvulsive status epilepticus (NCSE). Among 6 cases of convulsive patients, only 1 had epileptic discharge patterns of isoelectric, invariable low amplitude. Burst-suppression, persistent theta rhythm like background activity, persistent diffuse epileptic discharge and periodic waves had high mortality rate. CONCLUSION: Stroke is a major cause of consciousness disorders. And continuous VEEG monitoring is beneficial for clinical diagnosis, differential diagnosis and outcome evaluation. PMID- 26675796 TI - [Association between VAPB mutations and familial amyotrophic lateral sclerosis in Chinese patients]. AB - OBJECTIVE: To explore the mutations of VAPB (vesicle associated membrane protein/synaptobrevin associated membrane protein B) in Chinese patients with familial amyotrophic lateral sclerosis (FALS). METHODS: The clinical data were collected from 40 FALS families from 2008 to 2011 and the mutations of VAPB gene screened in probands using polymerase chain reaction (PCR) and direct sequencing. RESULTS: All 40 ALS families were of autosomal dominant inheritance. The male-to female ratio of probands was 1:0.7 and the average onset age (49 +/- 12) years. Upper limb onset accounted for 52.5%, lower limb onset 42.5% and bulbar onset 5.0%. No mutations were detected in VAPB gene. CONCLUSION: VAPB mutations are not a common cause and ALS8 is rare in Chinese FALS. PMID- 26675797 TI - [Effects of thymectomy on bone age and height development in juvenile myasthenia gravis]. AB - OBJECTIVE: To explore the effects of clinical indicators, particularly thymectomy on the development of juvenile myasthenia gravis (JMG) through the developmental status of bone age (BA) and height. METHODS: A cross-sectional study of 80 JMG patients was recruited to examine whether JMG patients had the abnormalities of height and bone development according to the distribution of height standard deviation score (Ht SDS) and BA. RESULTS: The mean BA was delayed by (0.15 +/- 1.32) years compared with patient chronological age (CA). The mean Ht SDS (HtCA SDS -1.25 +/- 1.03) was also lower than healthy controls. In multivariate analysis, the age at onset was negatively associated with delayed BA (P=0.007) whereas the cumulative intake of prednisone was negatively associated with HtCA SDS (P=0.043). No significant correlation existed between thymectomy and delayed BA or HtCA SDS. Delayed BA and slow growth existed in JMG patients. The age at onset of JMG was a correlative factor for delayed BA. And the intake of cumulative prednisone might be a determinant of height retardation. Thymectomy had no impact on the development of bone and height. CONCLUSION: We should pay more attention to monitoring BA and height in JMG patients to take appropriate therapeutic interventions. PMID- 26675798 TI - [Application of spatial working memory task fMRI in evaluation of primary insomnia patient's cognitive dysfunction]. AB - OBJECTIVE: To explore abnormal brain activation of spatial working memory in primary insomnia and its potential neuromechanism. METHODS: we recruited 30 cases primary insomnia (PI) patients and 30 cases age, gender matched healthy control (HC) subjects from July 2013 to December 2013, the diagnosis of primary insomnia matched the diagnosis criterion of DSM-IV and Classification and diagnostic criteria of mental disorders in China third edition (CCMD-3). All the subjects attended the tests of PSQI, HAMA, HAMD and index of spatial working memory. And then, we collected the data of routine MRI and spatial working memory task fMRI on 3.0 T MRI scanner. After that, we used SPM8 and REST1.8 to analyze the fMRI data, compared difference of PSQI, HAMA, HAMD, index of spatial working memory and brain activation of spatial working memory between PI group and HC group. RESULTS: There were significant difference between PI group and HC group in PSQI, HAMA, HAMD and index of spatial working memory (P < 0.05). In the spatial working memory related activate brain region, compared with HC group, left temporal lobe, occipital lobe and right frontal lobe activation increased and bilateral parahippocampalis, temporal cortex, frontal cortex and superior parietal lobule activation reduced in PI group. CONCLUSION: Spatial working memory task fMRI revealed the pathological mechanisms of cognitive dysfunction of clinical spatial working memory and emotional disorder in primary insomnia patients. PMID- 26675799 TI - [Pathological features of muscles and peripheral nerves of Kennedy's disease: a report of 12 cases]. AB - OBJECTIVE: To explore the pathological features of muscles and peripheral nerves of Kennedy's disease (KD). METHODS: A total of 12 male patients were selected at our department from January 2006 to October 2014. Their definite diagnoses of KD were made by genetic testing of androgen receptor. Their average age was (52 +/- 10) years old. All onset sites were lower limbs. Serum creatine kinase levels were elevated in varying degrees of 209-3 600 U/L. Electrophysiological examination revealed generalized neurogenic damage and impaired peripheral motor and sensory nerves. Biopsies were performed on biceps brachii (n=8), gastrocnemius (n=3), quadriceps femoris (n=1) and sural nerve (n=4). RESULTS: The major muscular pathological features were neurogenic pathological changes. Some patients had myopathic changes, showing necrotic fibers, regenerating fibers, fiber splitting, vortex-like fibers, central nuclei and reduced oxidase activities. Sural nerve pathology of 4 patients showed a loss of myelinated nerve fibers, as well as axonal degeneration, regeneration clusters and thin myelinated fibers. Electron microscopy examination showed axonal degeneration, regeneration clusters, thin myelinated fibers and onion bulbs-like pathological changes. CONCLUSION: KD has myopathic changes with an impairment of chronic axonal and demyelinating sensory nerves. PMID- 26675800 TI - [Hydrogen peroxide-induced changes of PPARgamma in primary cultured cortical neurons]. AB - OBJECTIVE: To investigate whether H2O2treatment negatively regulates PPARgamma in primary cortical neurons by increasing PPARgamma phosphorylation. METHODS: Primary cultured cortical neurons were treated with H2O2(250, 500, and 750 umol/L) for 2 h. 30 min before the H2O2(500 umol/L), the specific inhibitor of ERK1/2 activation, U0126, was added to the culture. Morphological observation, MTT assay and the trypan blue exclusion method were used to detect cell damage. Western blot was carried out to evaluate the expressions of p-PPARgamma (phospho PPARgamma) and total PPARgamma, as well as to investigate the nuclear translocation of PPARgamma (PPARgamma activity). RESULTS: (1) Compared with the control group, cell survival rates were decreased by H2O2at concentrations of 250, 500, and 750 umol/L (74.8% +/- 5.2%, 53.6% +/- 6.7% and 26.5% +/- 5.8%, respectively, P < 0.05), while cell death rate were increased (ctrl group 6.6% +/ 1.0%, H2O2-injured groups: 23.1% +/- 2.8%, 48.2% +/- 4.1% and 75.9% +/- 4.4% respectively, P < 0.05). (2) Compared with the control group, the expression of total PPARgamma failed to show significant change in H2O2-injured group, whereas the expression of p-PPARgamma increased. Neurons injured by H2O2(500 umol/L) also showed a reduction of PPARgamma nuclear translocation (an increase in cytosol PPARgamma and a simultaneous decrease in nuclear PPARgamma). (3) Compared with H2O2-injured group, inhibition of ERK1/2 activation decreased p-PPARgamma expression, and increased PPARgamma nuclear translocation, as well as improved cell survival rate (53.6% +/- 6.7% vs 70.8% +/- 1.3%, P < 0.05) and decreased cell death rate (48.2% +/- 4.1% vs 29.8%+/-3.4%, P < 0.05). CONCLUSION: Phosphorylation of PPARgamma may be involved in cell death induced by hydrogen peroxide in primary cultured cortical neurons. PMID- 26675801 TI - [Preparation of vanilline cross-linked rhBMP-2/chitosan microspheres and its effect on mesenchymal stem cells]. AB - OBJECTIVE: To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. METHODS: Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. RESULTS: The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 +/- 0.07 vs 0.73 +/- 0.05, P > 0.05; 48 h:1.19 +/- 0.11 vs 1.27 +/- 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP 2 was 216.1 +/- 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 +/- 0.07) and (0.68 +/- 0.06) umol pNPP.min-1.mg-1 protein respectively and both were higher than that of blank culture medium group (0.14 +/- 0.01) (P < 0.05). CONCLUSION: With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive. PMID- 26675802 TI - [Crosslinking modification of ultra high molecular weight polyethylene during joint arthroplasty]. AB - OBJECTIVE: To explore the optimal condition of crosslinking modification of ultra high molecular weight polyethylene (UHMWPE) by gamma ray irradiation. METHODS: The hip and knee joint samples of UHMWPE were tested with regards to friction and wear performance at different doses of (60)Co radiation and heat treatment. And the optimal condition of crosslinking was determined by wear performance and physicochemical properties. RESULTS: Under the condition of 75 kGy irradiation and 150 degrees C heat treatment, crosslinked UHMWPE showed the best performance. Acetabular sample wear rate decreased 63.24% and knee sample wear rate decreased 59.95% compared with conventional UHMWPE. The modified material had excellent mechanical properties of impact strength 83 kJ/m2, tensile strength 50.32 MPa, yield strength 21.83 MPa and elongation at break 312%. Also the material showed excellent antifatigue and reliable chemical properties. CONCLUSION: The optimal condition of crosslinking modification of UHMWPE is 75 kGy irradiation after 150 degrees C heat treatment. PMID- 26675803 TI - Genome-wide survey of putative RNA-binding proteins encoded in the human proteome. AB - RNA-binding proteins (RBPs) are involved in various post-transcriptional gene regulatory processes and are also functionally important members of the ribosome and the spliceosome. However, RBPs and their interactions with RNA are less well studied in comparison to DNA-binding proteins. We have classified the existing RBP structures, available in complexes with RNA and RNA/DNA hybrids, into different structural families and created Hidden Markov Models (HMMs). These structure-centric family HMMs, along with the sequence-centric family HMMs, were used as a primary database to systematically search the human proteome for the presence of putative RBPs. We have found more than 2600 gene products with RBP signatures in humans, of which around 28% are likely to bind to RNA but not DNA, whereas 9% might bind to both RNA and DNA. 11% of them do not contain an explicit functional annotation yet. Nearly 30% of the putative RBPs are exclusively nuclear, 15% have known disease associations and around 30% are enzymes. Around 40% of the proteins identified in this study are novel and have not been reported by recent large-scale studies on human RBPs. PMID- 26675804 TI - Nonflammable Alginate Nanocomposite Aerogels Prepared by a Simple Freeze-Drying and Post-Cross-Linking Method. AB - Nonflammable materials based on renewable ammonium alginate and nano fillers (nanoscale magnesium hydroxide, nanoscale aluminum hydroxide, layered double hydroxide, sodium montmorillonite, and Kaolin) were fabricated through a simple, environmentally friendly freeze-drying process, in which water was used as a solvent. A simple and economic post-cross-linking method was used to obtain homogeneous samples. The microstructure of the cross-linked alginate aerogels show three-dimensional networks. These materials exhibit low densities (0.064 0.116 g cm(-3)), low thermal conductivities (0.024-0.046 W/m K), and useful mechanical strengths (0.7-3.5 MPa). The aerogels also exhibit high thermal stabilities and achieve inherent nonflammability with limiting oxygen indexes (LOI) higher than 60. Related properties were conducted and analyzed by cone calorimeter (CC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). These results combine to suggest promising prospects for use of these aerogel nanocomposites in a range of applications. PMID- 26675805 TI - Association of the Family Nutrition and Physical Activity Screening Tool with Weight Status, Percent Body Fat, and Acanthosis Nigricans in Children from a Low Socioeconomic, Urban Community. AB - OBJECTIVE: OBJECTIVE: To examine the association of the Family Nutrition and Physical Activity (FNPA) screening tool with weight status, percent body fat, and acanthosis nigricans (AN) in 6- to 13-year-old children from a low socioeconomic, urban community. METHODS: Children (n=415) from four elementary schools located around Flint, Michigan were assessed for body mass index, percent body fat, and AN. The FNPA screening tool was completed by parents. Mann-Whitney U tests were used to assess differences in FNPA score by sex and presence of AN. Logistic regression was used to evaluate the association of the FNPA (tertiles) with weight status and AN. RESULTS: Children with AN (13.7%) had a significantly lower FNPA score (56.3 + 7.1) compared with children without AN (61.0 + 7.1; P<.05). Children with FNPA scores in the lowest tertile (high-risk) had odds ratios of 1.74 (95% CI =1.05 - 2.91) and 2.77 (95% CI =1.22 - 6.27) compared with children with FNPA scores in the highest tertile (low-risk) for being overfat and having AN, respectively. CONCLUSION: Although the FNPA screening tool did not predict risk for being overweight or obese, it was significantly associated with an increased odds of children at risk for being overfat or having AN. PMID- 26675806 TI - Answer to the question from page 235. PMID- 26675807 TI - Quantum correlations which imply causation. AB - In ordinary, non-relativistic, quantum physics, time enters only as a parameter and not as an observable: a state of a physical system is specified at a given time and then evolved according to the prescribed dynamics. While the state can, and usually does, extend across all space, it is only defined at one instant of time. Here we ask what would happen if we defined the notion of the quantum density matrix for multiple spatial and temporal measurements. We introduce the concept of a pseudo-density matrix (PDM) which treats space and time indiscriminately. This matrix in general fails to be positive for measurement events which do not occur simultaneously, motivating us to define a measure of causality that discriminates between spatial and temporal correlations. Important properties of this measure, such as monotonicity under local operations, are proved. Two qubit NMR experiments are presented that illustrate how a temporal pseudo-density matrix approaches a genuinely allowed density matrix as the amount of decoherence is increased between two consecutive measurements. PMID- 26675808 TI - Perspectives on zebrafish neurobehavioral pharmacology. PMID- 26675809 TI - [New options in adjuvant endocrine therapy in breast cancer]. AB - Endocrine therapy is a compulsory step in the adjuvant management of early breast cancer expressing the estrogen receptor, by reducing as much as possible serum and tissue levels of estrogens. Tamoxifen is the standard therapy for non menopausal women. Ovarian function suppression, in addition to exemestane or tamoxifen, could be an alternative option for young women at high risk of recurrence and non menopausal after adjuvant or neo-adjuvant chemotherapy. Recent studies show a trend for improvement of overall survival and disease-free survival with aromatase inhibitors among postmenopausal women. However, safety of aromatase inhibitors is controversial and adverse events may lead to switch for tamoxifen with no loss of efficacy. Extension therapy by tamoxifen or aromatase inhibitor after five years of tamoxifen and for a total duration of ten years significantly improves overall survival. There is to date no data supporting the extension therapy after five years of aromatase inhibitor. PMID- 26675810 TI - Wrist ultrasound examination - scanning technique and ultrasound anatomy. Part 1: Dorsal wrist. AB - Ultrasound imaging of the musculoskeletal system is superior to other imaging methods in many aspects, such as multidimensional character of imaging, possibility of dynamic evaluation and precise assessment of soft tissues. Moreover, it is a safe and relatively inexpensive method, broadly available and well-tolerated by patients. A correctly conducted ultrasound examination of the wrist delivers detailed information concerning the condition of tendons, muscles, ligaments, nerves and vessels. However, the knowledge of anatomy is crucial to establish a correct ultrasound diagnosis, also in wrist assessment. An ultrasound examination of the wrist is one of the most common US examinations conducted in patients with rheumatological diseases. Ultrasonographic signs depend on the advancement of the disease. The examination is equally frequently conducted in patients with pain or swelling of the wrist due to non-rheumatological causes. The aim of this publication was to present ultrasound images and anatomic schemes corresponding to them. The correct scanning technique of the dorsal part of the wrist was discussed and some practical tips, thanks to which highly diagnostic images can be obtained, were presented. The following anatomical structures should be visualized in an ultrasound examination of the dorsal wrist: distal radio-ulnar joint, radiocarpal joint, midcarpal joint, carpometacarpal joints, dorsal radiocarpal ligament, compartments of extensor tendons, radial artery, cephalic vein, two small branches of the radial nerve: superficial and deep, as well as certain midcarpal ligaments, particularly the scapholunate ligament and lunotriquetral ligament. The paper was distinguished in 2014 as the "poster of the month" (poster number C-1896) during the poster session of the European Congress of Radiology in Vienna. PMID- 26675811 TI - Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer: An In Vivo Animal Study. AB - OBJECTIVES: This study investigates (1) local tumor control and (2) normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR) for recurrent lung cancer. METHODS: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1) control (n = 10), (2) conventional radiotherapy (RT; n = 10), and (3) PLDR (n = 10). Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10) or 40 * 0.2 Gy pulses with 3-minute intervals (n = 10). RESULTS: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P < .05). The PLDR results were slightly better than conventional RT (8% difference in the mean tumor volume; P > .05). For study 2, the average weight was 20.94 +/- 1.68 g and 25.69 +/- 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05), respectively. CONCLUSION: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. ADVANCES IN KNOWLEDGE: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques. PMID- 26675812 TI - Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S associated Parkinson's disease. AB - Patients with Parkinson's disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated PD. PMID- 26675813 TI - Assessing the role of TUBA4A gene in frontotemporal degeneration. AB - The tubulin alpha 4a (TUBA4A) gene has been recently associated with amyotrophic lateral sclerosis. Interestingly, some of the mutation carriers were also diagnosed with frontotemporal degeneration (FTD) or mild cognitive impairment. With the aim to investigate the role of TUBA4A in FTD, we screened TUBA4A in a series of 814 FTD patients from Spain. Our data did not disclose any nonsense or missense variant in the cohort, thus suggesting that TUBA4A mutations are not associated with FTD. PMID- 26675814 TI - Identification of mutation in GTPBP2 in patients of a family with neurodegeneration accompanied by iron deposition in the brain. AB - We aimed to identify the genetic cause of a neurologic disorder accompanied with mental deficiency in a consanguineous family with 3 affected siblings by linkage analysis and exome sequencing. Iron accumulation in the brain of the patients was a notable phenotypic feature. A full-field electroretinography revealed generalized dysfunction of photoreceptors, bipolar cells, and amacrine cells. A splice site mutation in GTPBP2 that encodes GTP-binding protein 2 was identified in the patients and considered possible cause of their disease. The mutation was empirically shown to cause deletion of exon 9 of the gene and result in production of a truncated protein-lacking conserved C-terminus domains. GTPBP2 is a member of the GTPase superfamily of proteins. A recent report of identification of another splice site mutation in GTPBP2 in mice that causes neurodegeneration, and retinal damage provides supportive evidence for our finding. The conditions in the affected individuals of the family studied may define a novel form of neurodegeneration with brain iron accumulation, and GTPBP2 may be a novel neurodegeneration with brain iron accumulation gene. PMID- 26675815 TI - Inverse Psoriasiform Eruption During Pembrolizumab Therapy for Metastatic Melanoma. PMID- 26675816 TI - Factors Associated with Bacterial Vaginosis among Women Who Have Sex with Women: A Systematic Review. AB - BACKGROUND: Women who have sex with women (WSW) have a higher burden of bacterial vaginosis (BV) than heterosexual women; studies of risk factors specific to this population are limited. We summarised current knowledge regarding risk factors for BV among WSW by systematic review. METHODS: This systematic review was conducted according to the PRISMA statement. PUBMED, EMBASE, Web of Science and The Cochrane Library were searched to 31st December, 2014. INCLUSION CRITERIA: 1) WSW included in the study population; 2) accepted BV diagnostic method; 3) investigated or could extrapolate factors(s) associated with BV acquisition, persistence or transmission in WSW specifically by comparing BV positive to BV negative women. Search was limited to English-language publications. RESULTS: A limited number of studies have investigated BV in WSW. Of 71 unique references, 18 full-text articles were assessed and 14 studies fulfilled inclusion criteria. BV was positively associated with higher numbers of female partners, both lifetime and in the three months prior to diagnosis, and confirmed BV in a female partner, but inconsistently associated with partners' BV history or symptoms. BV was not associated with ethnicity, vaginal douching or hormonal contraception. The impact of specific sexual activities, male sexual contact, smoking and the menstrual cycle varied considerably between study populations. CONCLUSION: BV in WSW is associated with increased numbers of recent and past female partners and confirmed BV in a female partner. There are limited studies of BV in WSW populations, and research is needed to further elucidate risk factors for BV among WSW. However these data provide epidemiological evidence that BV risk in women is directly related to exposure to other female partners and a partner with BV, providing support for the concept that BV is likely to be transmitted between women. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014009536 (PROSPERO). PMID- 26675818 TI - Is Total Knee Arthroplasty a Viable Treatment Option in Octogenarians with Advanced Osteoarthritis? AB - PURPOSE: This study directly compared clinical assessment scores and short-term systemic complications after total knee arthroplasty (TKA) between a group of patients aged 80 or older (141 patients) and another group of patients aged between 65 and 70 years (616 patients) with advanced osteoarthritis. MATERIALS AND METHODS: We retrospectively investigated 757 osteoarthritic patients who underwent primary TKA from January 2007 to January 2011 with a follow-up of 1 year. The surgery was performed using an extramedullary alignment guide instrument without invasion of the intramedullary canal to decrease embolic load and blood loss. RESULTS: At 1 year after surgery, the mean Knee Society knee score was improved in both groups (from 63.6 to 83.2 in octogenarians and from 68.3 to 89.0 in the younger group) and the level of satisfaction was excellent in both groups (8 in octogenarians and 8.3 in the younger group), even though there was no notable change in function score in the octogenarians (from 61.0 to 61.9 in the octogenarians and from 62.3 to 73.6 in the younger group). The total incidence of systemic complications (3.4% vs. 1.2%, p=0.400) and surgical complications (2.1% vs. 0.5%, p=0.229) showed no significant difference between groups. CONCLUSIONS: TKA yielded favorable clinical outcomes with a comparatively low postoperative complication rate in octogenarians despite the negligible functional improvement. PMID- 26675819 TI - Soluble Moringa oleifera leaf extract reduces intracellular cadmium accumulation and oxidative stress in Saccharomyces cerevisiae. AB - Moringa oleifera leaves are a well-known source of antioxidants and traditionally used for medicinal applications. In the present study, the protective action of soluble M. oleifera leaf extract (MOLE) against cadmium toxicity was investigated in the model eukaryote Saccharomyces cerevisiae. The results showed that this extract exhibited a protective effect against oxidative stress induced by cadmium and H2O2 through the reduction of intracellular reactive oxygen species. Interestingly, not only the co-exposure of soluble MOLE with cadmium but also pretreatment of this extract prior to cadmium exposure significantly reduced the cadmium uptake through an inhibition of Fet4p, a low-affinity iron(II) transporter. In addition, the supplementation of soluble MOLE significantly reduced intracellular iron accumulation in a Fet4p-independent manner. Our findings suggest the potential use of soluble extract from M. oleifera leaves as a dietary supplement for protection against cadmium accumulation and oxidative stress. PMID- 26675820 TI - Nonequilibrium spin injection in monolayer black phosphorus. AB - Monolayer black phosphorus (MBP) is an interesting emerging electronic material with a direct band gap and relatively high carrier mobility. In this work we report a theoretical investigation of nonequilibrium spin injection and spin polarized quantum transport in MBP from ferromagnetic Ni contacts, in two dimensional magnetic tunneling structures. We investigate physical properties such as the spin injection efficiency, the tunnel magnetoresistance ratio, spin polarized currents, charge currents and transmission coefficients as a function of external bias voltage, for two different device contact structures where MBP is contacted by Ni(111) and by Ni(100). While both structures are predicted to give respectable spin-polarized quantum transport, the Ni(100)/MBP/Ni(100) trilayer has the superior properties where the spin injection and magnetoresistance ratio maintains almost a constant value against the bias voltage. The nonequilibrium quantum transport phenomenon is understood by analyzing the transmission spectrum at nonequilibrium. PMID- 26675817 TI - The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation. AB - BACKGROUND: The aim of this study was to discern whether a relation between biochemical parameters, sonography and musculoskeletal data exists in cases of hyperthyroidism and whether they are modifiable through supplementation with selenomethionine and magnesium citrate as well as by acupuncture and manual medicine methods. RESULTS: A direct correlation between whole blood selenium and serum magnesium was found in subjects without thyroid disease and in menopausal women while it was reversed in cases of thyroid diseases as well as in patients with depression, infection, and in infertile women. Vascularization indices were elevated in cases of newly diagnosed benign thyroid diseases. Musculoskeletal changes i.e. lateral tension and idiopathic moving toes, as well as situations of physical and psychological stress and minor trauma and infection led to an increase of vascularization. Magnesium levels correlated negatively with these two conditions. The supplementation brought a reduction of the vascularization indices and reduced the incidence of idiopathic moving toes. Treatment of lateral tension required manual medicine methods and acupuncture (gastrocnemius). A small subgroup of patients showed a further reduction of hyper-vascularization after receiving coenzyme Q10. CONCLUSIONS: We interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10. PMID- 26675823 TI - Racial differences in the association between nonmedical prescription opioid use, abuse/dependence, and major depression. AB - BACKGROUND: African Americans (AAs) have lower rates of depressive disorders and are less likely to receive opioid analgesics for chronic pain than whites. Given the evidence that prescription opioid use is associated with depression, we hypothesized that the opioid abuse/dependence and depression comorbidity would be less common among AAs compared with whites. METHODS: A cross-sectional secondary analysis of the public use files for the 2012 (n = 55,268) and 2013 (n = 55,160) National Survey on Drug Use and Health (NSDUH) was used to obtain past-year, DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria diagnoses of nonmedical prescription opioid use (NMPOU), abuse/dependence, and major depressive episode (MDE). Covariates included anxiety disorder, alcohol and illicit drug abuse/dependence, smoking, age, gender, education, marital status, health insurance, county urbanicity, and income. Logistic regression models estimating the association between opioid use and MDE were computed before and after adjusting for covariates and separately for AAs and whites. RESULTS: AAs and whites had similar past-year prevalence of NMPOU (3.5% vs. 3.7%) and abuse/dependence (0.7% vs. 0.9%). MDE was significantly more prevalent among whites (7.4% vs. 5.5%; P < .0001). Among whites, NMPOU and abuse/dependence were associated with MDE (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.12-1.64 and OR = 2.22, 95% CI = 1.67-2.94, respectively). Among AAs, there were no significant associations between NMPOU, abuse/dependence, and MDE (OR range: 0.80-0.95). CONCLUSIONS: In a nationally representative sample, co occurrence of past-year depression, NMPOU, and abuse/dependence was determined in whites but not AAs. Additional research is needed to establish the contribution of pain and temporal relationships. PMID- 26675821 TI - From nerve net to nerve ring, nerve cord and brain--evolution of the nervous system. AB - The puzzle of how complex nervous systems emerged remains unsolved. Comparative studies of neurodevelopment in cnidarians and bilaterians suggest that this process began with distinct integration centres that evolved on opposite ends of an initial nerve net. The 'apical nervous system' controlled general body physiology, and the 'blastoporal nervous system' coordinated feeding movements and locomotion. We propose that expansion, integration and fusion of these centres gave rise to the bilaterian nerve cord and brain. PMID- 26675824 TI - Estimating the Attack Ratio of Dengue Epidemics under Time-varying Force of Infection using Aggregated Notification Data. AB - Quantifying the attack ratio of disease is key to epidemiological inference and public health planning. For multi-serotype pathogens, however, different levels of serotype-specific immunity make it difficult to assess the population at risk. In this paper we propose a Bayesian method for estimation of the attack ratio of an epidemic and the initial fraction of susceptibles using aggregated incidence data. We derive the probability distribution of the effective reproductive number, Rt, and use MCMC to obtain posterior distributions of the parameters of a single-strain SIR transmission model with time-varying force of infection. Our method is showcased in a data set consisting of 18 years of dengue incidence in the city of Rio de Janeiro, Brazil. We demonstrate that it is possible to learn about the initial fraction of susceptibles and the attack ratio even in the absence of serotype specific data. On the other hand, the information provided by this approach is limited, stressing the need for detailed serological surveys to characterise the distribution of serotype-specific immunity in the population. PMID- 26675834 TI - Electrochemistry of layered GaSe and GeS: applications to ORR, OER and HER. AB - Though many studies examined the properties of the class of IIIA-VIA and IVA-VIA layered materials, few have delved into the electrochemical aspect of such materials. In light of the burgeoning interest in layered structures towards various electrocatalytic applications, we endeavored to study the inherent electrochemical properties of representative layered materials of this class, GaSe and GeS, and their impact towards electrochemical sensing of redox probes as well as catalysis of oxygen reduction, oxygen evolution and hydrogen evolution reactions. In contrast to the typical sandwich structure of MoS2 layered materials, GeS is isoelectronic to black phosphorus with the same structure; GaSe is a layered material consisting of GaSe sheets bonded in the sequence Se-Ga-Ga Se. We characterized GaSe and GeS by employing scanning electron microscopy, X ray diffraction, Raman spectroscopy and X-ray photoelectron spectroscopy complemented by electronic structure calculations. It was found that the encompassing surface oxide layers on GaSe and GeS greatly influenced their electrochemical properties, especially their electrocatalytic capabilities towards hydrogen evolution reaction. These findings provide fresh insight into the electrochemical properties of these IIIA-VIA and IVA-VIA layered structures which enables development for future applications. PMID- 26675822 TI - Neurobiology of rodent self-grooming and its value for translational neuroscience. AB - Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self grooming, and we highlight studies of rodent models of neuropsychiatric disorders -including models of autism spectrum disorder and obsessive compulsive disorder- that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action. PMID- 26675825 TI - Modification of COMT-dependent pain sensitivity by psychological stress and sex. AB - Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity. PMID- 26675835 TI - Management of carotid near-occlusion and acute carotid occlusion. AB - As a stenosis becomes more severe, blood flow through it increases in velocity to maintain volume, flow and pressure. But there is a critical point beyond which further increase in stenosis no longer allows sufficient blood to pass through to maintain volumetric flow, and the carotid artery beyond the stenosis begins to decrease in diameter. This is the near occlusion. To maintain a sufficient blood flow in affected area, there is a progressive recruitment of collaterals followed by an activation of cerebral autoregulation with dilatation of resistance vessels. When this process fails to maintain normal cerebral blood flow, oxygen extraction fraction of the affected brain tissue increases to maintain normal cerebral metabolism. Near occlusion has been described as involving 1 to 10% of all severe stenosis, but the potential for stroke from such critical stenosis is less than its appearance would suggest. The optimum management of near-occlusion therefore remains a matter of debate. Although endarterectomy for carotid stenosis of 70-99% was associated with an absolute risk reduction in any stroke or death of 16% in the original randomized trials, the benefit was less in patients with near-occlusion. In 2015, a meta-analysis focused on patients with near-occlusion confirmed only a small benefit of carotid endarterectomy or stenting compared to medical treatment in patients with near occlusion. In patients with near-occlusion and compromised hemodynamics, revascularization should improve cerebral blood flow and consequently prevent ischemic stroke. Nevertheless the effect of improved cerebral hemodynamics after revascularization on prevention of ischemic stroke is uncertain. PMID- 26675826 TI - Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease. AB - Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 MUM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED. PMID- 26675836 TI - Radial access for endovascular ilio-femoral procedures. AB - Common femoral artery puncture for ilio-femoral angioplasty can be hazardous or cumbersome in specific situations that require upper limb access (presence of a hostile groin, previous femoral surgery, cross-over maneuver in the setting of bifurcated aortic graft or pre-existing iliac kissing stents). The brachial artery is an alternative access site that is burdened with significant local complication rates. As in the coronary setting, feasibility and safety of transradial peripheral angioplasty has been reported in the recent literature. Procedural success rates ranged from 87% to 100%. No major access site bleeding was observed. Procedure and fluoroscopy time were not substantially increased, and decreased along with the learning curve. The majority of reports were limited to iliac lesions treatment, due to the lack of long-shaft and dedicated devices. Our experience showed the feasibility of this technique in iliac lesions but also in superficial femoral and popliteal artery procedures. Radial access can be used in situations where femoral approach is unsuitable and as first-line approach in the setting of ambulatory procedures. Although devices evolve, main limitations remain related to the lack of longer introducer sheaths and the absence of specific rescue devices and drug-eluting balloons. As a conclusion, radial access for endovascular ilio-femoral procedures is currently a promising alternative to femoral and humeral access in selected patients with the possibility of same-day discharge, and could progressively be considered when planning peripheral procedures. PMID- 26675837 TI - For which peripheral lesions could we consider drug eluting stents? AB - Intimal hyperplasia is a physiologic response to wall injury and represents the essential weak point of endovascular treatment. In the coronary segment, drug eluting stents (DES) have shown their effectiveness in suppressing this response and the transfer of this technique into the peripheral vasculature was mandatory, but the available data are conflictive and necessitate critical analysis. Peripheral DES related data from randomized or non randomized trials, published or presented, have been reviewed concerning the outcome in terms of "primary patency", "clinical benefit" and "limb salvage". Further inquiry was performed concerning data from material testing. The majority of study endpoints e.g. primary patency and freedom from target lesion revascularization (TLR) comply with the coronary paradigm to prevent restenosis and the peripheral DES proved this concept on an individual basis. DES meta-analytical results remain inconclusive and could not reveal superiority of DES for clinical endpoints such as limb salvage or mortality. DES differ significantly in prevention of restenosis and occurrence of severe adverse events which does impede the clinical and economic evaluations. DES related data are conflicting and partially contradicting the widespread use of this technique. The positive effect of DES in terms of patency and freedom from TLR could not achieve an omnipresent clinical correlate. Technical challenges such as availability of appropriate device length, coating related material fatigue or particulate embolization and delayed intimalization remain an issue and mandate an individual evaluation within a blinded prospective randomized study to minimize bias. PMID- 26675838 TI - Effects of origin and season on the lipids and sensory quality of European whitefish (Coregonus lavaretus). AB - The effect of variation in origin and season on the lipids and sensory quality of European whitefish (Coregonus lavaretus) was studied. The proportion of docosahexaenoic acid (22:6n-3) of the total phospholipid fatty acids in fillets was considerably higher in spring compared with autumn. Farmed fish contained 3-4 times more lipids than wild fish. Combined, the fillets of farmed fish contained 2-3 times more eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid than the fillets of wild fish. Contents of vitamin D were high both in farmed and wild fish. Aroma of raw farmed whitefish was less algae-like than wild one. Raw farmed whitefish was harder, less springy, and lighter in flesh color than wild whitefish. Cooked, farmed fish had slightly stronger flavor than wild fish. There was no significant difference in pleasantness between whitefish of different origin in any of the evaluated characteristics. Both farmed and wild European whitefish caught in autumn and spring proved to have a high content of n-3 fatty acids and vitamin D, and hence they serve as a good source of nutritionally important lipids. PMID- 26675839 TI - Factors influencing the formation of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine: Temperature, alcoholic degree, and amino acids concentration. AB - The validation of a HPLC-PDA-MS/MS chromatographic method for the quali/quantitative characterization of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine has been described and discussed. Four standards showed a good linearity with high correlation coefficient values (over 0.9989) and LOD and LOQ were 0.001-0.015 mg/L and 0.004-0.045 mg/L, respectively. Furthermore, this study reported how factors such as temperature, alcoholic degree, and amino acids concentration are able to influence the formation of these four alcohols in Monastrell wines. The quantification values of these alcohols has been detected both at the half and end of alcoholic fermentation, and at the end of malolactic fermentation. In relation to interactions between factors, several significant variations emerged (p ? 0.001). The impact of amino acids supplementation in Monastrell must it has been demonstrated, mainly in regards to histaminol and tryptophol. PMID- 26675840 TI - Biotransformation effects on anti lipogenic activity of citrus extracts. AB - Citrus peel is a good source of flavonoids, with higher content in relation to pulp. This study proposed to investigate the anti-lipogenic potential of a newly developed citrus flavonoids extract, obtained from citrus industrial residue, bioprocessed in order to generate a commercial source of some flavonoids naturally found in low quantity. The results showed that the citrus peel extract obtained after biotransformation was a good source of hesperitin and naringenin, flavonoids that has no source for production on a large scale, as in supplements or medicines. Still, the results showed that all extracts could be used in obesity treatment. The original extract, "In Natura", would be useful to reduce new adipocytes synthesis and lipid accumulation, and the extract bioprocessed, "Biotransformed" extract could be used to induce lipolysis on fat tissue. PMID- 26675841 TI - Optimization of ultrasound-assisted extraction to obtain mycosterols from Agaricus bisporus L. by response surface methodology and comparison with conventional Soxhlet extraction. AB - Ergosterol, a molecule with high commercial value, is the most abundant mycosterol in Agaricus bisporus L. To replace common conventional extraction techniques (e.g. Soxhlet), the present study reports the optimal ultrasound assisted extraction conditions for ergosterol. After preliminary tests, the results showed that solvents, time and ultrasound power altered the extraction efficiency. Using response surface methodology, models were developed to investigate the favourable experimental conditions that maximize the extraction efficiency. All statistical criteria demonstrated the validity of the proposed models. Overall, ultrasound-assisted extraction with ethanol at 375 W during 15 min proved to be as efficient as the Soxhlet extraction, yielding 671.5 +/- 0.5mg ergosterol/100 g dw. However, with n-hexane extracts with higher purity (mg ergosterol/g extract) were obtained. Finally, it was proposed for the removal of the saponification step, which simplifies the extraction process and makes it more feasible for its industrial transference. PMID- 26675842 TI - Using beta-cyclodextrin/attapulgite-immobilized ionic liquid as sorbent in dispersive solid-phase microextraction to detect the benzoylurea insecticide contents of honey and tea beverages. AB - A green, simple, inexpensive dispersive solid-phase microextraction method coupled with high-performance liquid chromatography was developed for rapid screening and selective recognition of benzoylurea insecticides (BUs) in honey and tea beverages. A novel adsorbent, ionic liquid (IL)-modified beta cyclodextrin/attapulgite (beta-CD/ATP), was prepared by immobilizing IL on the surface of beta-CD/ATP. A series of demanding extraction conditions were investigated through the experimental design. Under optimum conditions, the limits of detection for the analytes varied from 0.12 to 0.21 MUg L(-1). The enrichment factors ranged from 112 to 150 folds. Linearities in the range of 5 500 ng m L(-1) were achieved for four BUs, while the correlation coefficients ranged from 0.9997 to 1.0000 and the recoveries from 84.5% to 104.7%. The precision of this method for the four BUs corresponded to intra-day and inter-day RSDs% lower than 3.85%. Finally, the proposed technique was applied for the preconcentration of the BUs from real samples with satisfactory results. PMID- 26675843 TI - Inactive dry yeast application on grapes modify Sauvignon Blanc wine aroma. AB - This study investigated the potential to improve wine aroma by applying two inactive dry yeast products (IDYs) at the onset of ripening on Sauvignon Blanc grapes. Both products led to increased reduced glutathione concentrations in the grape juice and corresponding wines, as well as differences in individual higher alcohol acetates (HAAs) and ethyl esters of straight chain fatty acids (EEFAs) at the end of fermentation. After two months of storage, a significantly slower decrease of EEFAs and to a lesser extent of HAAs was found for wines made from grapes with IDY applications. These wines also resulted in significantly slower synthesis of ethyl esters of branched acids, whereas varietal thiols were altered in a product-specific manner. The modifications in the wine chemical composition were also sensorially corroborated. This study showed that vineyard additions of IDY products directly on the grapes at the onset of ripening have a subsequent benefit to the production and preservation of aroma in wines. PMID- 26675844 TI - A phenylacetaldehyde-flavonoid adduct, 8-C-(E-phenylethenyl)-norartocarpetin, exhibits intrinsic apoptosis and MAPK pathways-related anticancer potential on HepG2, SMMC-7721 and QGY-7703. AB - Norartocarpetin, quercetin and naringenin were found to effectively inhibit 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation through trapping its phenylacetaldehyde and form their adducts in roast beef patties. Six adducts [8-C- or 6-C-(E-phenylethenyl) flavonoids] formed between phenylacetaldehyde and three flavonoids were detected in roast beef patties by UPLC-MS analyses and compared with their synthetic references. These flavonoid-phenylacetaldehyde adducts were synthesised and further subjected to cytotoxicity tests on three liver cancer cell lines HepG2, SMMC-7721 and QGY-7703. The adduct 8-C-(E phenylethenyl)norartocarpetin (NARA1) was found to significantly induce cancer cell death with IC50 values about 7 MUM. After pre-treating with MAPK and caspase inhibitors, alteration of the cell morphology and cleaved-PARP were detected in liver cancer cell lines administered with NARA1. These data indicated that norartocarpetin could inhibit PhIP formation in roast beef patties and form norartocarpetin-phenylacetaldehyde adducts. The adduct NARA1 has anticancer potential via intrinsic caspase-dependent and cell context-dependent MAPKs pathways. PMID- 26675845 TI - Use of multiparametric magnetic resonance microscopy for discrimination among different processing protocols and anatomical positions of Slovenian dry-cured hams. AB - A novel multiparametric magnetic resonance microscopy (MRM) approach was applied to the Slovenian Kraski prsut dry-cured ham samples in order to evaluate its potential for discrimination among biceps femoris and semimembranosus muscle from two hams, differing in processing (salting duration) and thus in water and salt content. The approach is based on apparent diffusion coefficient (ADC) mapping as well as on longitudinal (T1) and transversal (T2) nuclear magnetic resonance relaxation time mapping. Three-dimensional maps were acquired and analyzed by one dimensional (1D) ADC, T1, and T2 distributions as well as by paired two dimensional ADC-T1, ADC-T2 and T1-T2 distributions. The discriminating potential of the applied MRM approach was confirmed by differences among both 1D and 2D distributions of different ham samples. In addition, distribution peak positions highly correlated with the conventionally determined moisture content. PMID- 26675846 TI - Grapevine-shoot stilbene extract as a preservative in red wine. AB - This paper reports the use of a grapevine-shoot stilbene extract (Vineatrol(r)) as a preservative in red wine. Its effectiveness to preserve red wine quality under two different winemaking systems (traditional and Ganimede) was studied at bottling and after twelve months of storage in bottle. Enological parameters, color related parameters, volatile composition, sensory analysis and olfactometric profile were evaluated. At bottling wines treated with Vineatrol showed higher color related parameters and higher score in sensory analysis than those treated with SO2. The use of SO2 increased ester and alcohol volatile compounds in relation to the use of Vineatrol. Wine olfactometric profile was modified by Vineatrol addition. Two new odorant zones with high modified frequency appeared in wines treated with Vineatrol. After 12months of storage in bottle, wines treated with Vineatrol showed parameters related to oxidation. The weak point of the process seemed to be the evolution during the storage in bottle. PMID- 26675847 TI - Determination and quality evaluation of green tea extracts through qualitative and quantitative analysis of multi-components by single marker (QAMS). AB - The quality of tea is mainly attributed to tea polyphenols and caffeine. In this paper, a new strategy for quality evaluation of green tea extracts was explored and verified through qualitative and quantitative analysis of multi-components by single marker (QAMS). Taguchi Design was introduced to evaluate the fluctuations of the relative conversion factors (fx) of tea catechins, gallic acid and caffeine to epigallocatechin gallate. The regression model (Sig.=0.000) and the deviations (R(2)>0.999) between QAMS and normal external standard method proved the consistency of the two methods. Hierarchical cluster analysis and canonical discriminant analysis were employed to classify 26 batches of commercial Longjing green tea extracts (LJGTEs) collected from different producers. The results showed a significant difference in component profile between the samples from different origins. The QAMS method was verified to be an alternative and promising method to comprehensively and effectively control the quality of LJGTEs from different origins. PMID- 26675848 TI - Antioxidant activities of crude extracts of fucoidan extracted from Sargassum glaucescens by a compressional-puffing-hydrothermal extraction process. AB - Fucoidan, a multifunctional marine polymer, is normally extracted from brown algae via extensive use of acid, solvent or high temperature water and a long reaction time. In present study, we developed a novel compressional-puffing hydrothermal extraction (CPHE) process which primarily decomposes the cellular structure of algae and facilitates the release of fucoidan by hot water extraction. The CPHE process provides a number of advantages including simple procedure, reactant-saving, reduced pollution, and feasibility for continuous production. Sargassum glaucescens (SG) was utilized in this study, and the maximum extraction yield of polysaccharide was approximately 9.83 +/- 0.11% (SG4). Thin layer chromatography (TLC), Fourier transform infrared (FTIR) analysis, and measurements of monosaccharide composition, fucose, sulfate, and uronic acid contents revealed that the extracted polysaccharide showed characteristics of fucoidan. All extracts exhibited antioxidant activities, and thus, further exploration of these extracts as potential natural and safe antioxidant agents is warranted. PMID- 26675849 TI - Effects of salts on oxidative stability of lipids in Tween-20 stabilized oil-in water emulsions. AB - Lipid oxidation in oil-in-water (O/W) emulsions is an important factor determining the shelf life of food products. Salts are often present in many types of emulsion based food products. However, there is limited information on influence of salts on lipid oxidation in O/W emulsions. Thus, the purpose of this study was to examine the effects of sodium and potassium chloride on lipid oxidation in O/W emulsions. Tween 20 stabilized corn O/W emulsions at pH 7.0 were prepared with different concentrations of sodium chloride with or without the metal chelators. NaCl did not cause any changes in emulsion droplet size. NaCl dose-dependently promoted lipid oxidation as measured by the lipid oxidation product, hexanal. Both deferoxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) reduced lipid oxidation in emulsions with NaCl, with EDTA being more effective. Potassium chloride showed similar impact on lipid oxidation as sodium chloride. These results suggest that salts are able to promote lipid oxidation in emulsions and this effect can be controlled by metal chelators. PMID- 26675850 TI - Surfactant-free solid dispersion of fat-soluble flavour in an amorphous sugar matrix. AB - A solid dispersion technique to homogeneously disperse hydrophobic ingredients in a water-soluble solid without using surfactant was examined as follows: first, freeze-dried amorphous sugar was dissolved in an organic medium that contained a soluble model hydrophobic component. Second, the mixed solution of sugar and the model hydrophobic component was vacuum dried into a solid (solid dispersion). Methanol and six fat-soluble flavours, including cinnamaldehyde, were used as organic media and model hydrophobic components. The retention of flavours in the solid dispersion during drying and storage under vacuum was evaluated. The amorphised disaccharides dissolved in methanol up to 100mg/mL, even temporarily (20s to 10 days) and could be solidified without any evidence of crystallisation and segregation from flavour. The solid dispersion, prepared using alpha-maltose usually showed 65-95% flavour retention during drying (and storage for cinnamaldehyde), whereas ? 50% of the flavour was lost when the flavour was O/W emulsified with a surfactant and then freeze-dried with sugar. PMID- 26675851 TI - Glucosamine-induced glycation of hydrolysed meat proteins in the presence or absence of transglutaminase: Chemical modifications and taste-enhancing activity. AB - Salt reduction in food is a challenging task. The food processing sector has adopted taste enhancers to replace salt partially. In this study, a flavour enhancer formulation (liquid seasoning) was produced using enzymatically hydrolysed poultry proteins isolate (PPI). The PPI obtained through the isoelectric solubilisation precipitation process (ISP) was hydrolysed with Alcalase and glycated with glucosamine (GlcN) at moderate temperatures (37/50 degrees C) in the presence or absence of transglutaminase (TGase). The glycated hydrolysates showed reduced fluorescence advanced glycated end-products (AGE) and a reduced amount of alpha-dicarbonyl compounds (alpha-DC). An untrained consumer panel ranked the meat protein hydrolysate seasoning saltier than the salty standard seasoning solution (p<0.05) regardless of GlcN glycation (both tested at 0.3M Na(+)). GlcN treatments showed a tendency (p=0.0593) to increase savouriness. Free glutamic acid and free aspartic acid found in the PPI hydrolysate likely increased the salty perception. PMID- 26675852 TI - Polyphenols, antioxidants, and antimutagenic effects of Copaifera langsdorffii fruit. AB - Copaifera langsdorffii (copaiba) is a Brazilian exotic fruit, poorly studied regarding its bioactive composition. The aim of this study was to determine bioactive compounds, antioxidant and antimutagenic activities of copaiba pulp. The samples were extracted with different solvents in order to analyze polyphenol compounds (Folin Ciocalteau and HPLC-DAD), total flavonoids (reaction with AlCl3) and antioxidant capacity (FRAP, ORAC, DPPH). The copaiba fruit showed high polyphenol content and antioxidant capacity. Phenolic compounds, such as gallic acid, epicatechin gallate, catechin, epicatechin and isoquercitrin, were identified in the copaiba pulp. Despite the antioxidant capacity, the highest dose of copaiba showed no antimutagenic effects in the in vivo study. The dose which showed antimutagenic activity was 100 mg kg(-1). PMID- 26675853 TI - Identification and characterization of antioxidant peptides obtained by gastrointestinal digestion of amaranth proteins. AB - The objective of the present work was to separate and identify antioxidant peptides from a simulated gastrointestinal digest (Id) from Amaranthus mantegazzianus proteins (I), which has previously been demonstrated to have this activity. I and Id were separated by preparative RP-HPLC. Fractions were evaluated by the ORAC method and the more active ones were analyzed by LC-MS/MS. Each fraction presented diverse peptides from different proteins, most of them from the 11S globulin. After grouping the peptides from 11S globulin according to their overlapping sequences, and based on previous information about structure activity relationships, ten sequences were synthesized, in order to evaluate their antioxidant activity. Four peptides presented interesting activity: AWEEREQGSR>YLAGKPQQEH~IYIEQGNGITGM~TEVWDSNEQ. They exhibited some of the structural characteristics already known to demonstrate this activity, all of them containing at least one bulky aromatic residue. All belonged to little structured, internal or exposed regions of the acid subunit of the 11S globulin. PMID- 26675854 TI - Sucrose quantitative and qualitative analysis from tastant mixtures based on Cu foam electrode and stochastic resonance. AB - Quantitative and qualitative determination of sucrose from complex tastant mixtures using Cu foam electrode was investigated in this study. Cu foam was prepared and its three-dimensional (3-D) mesh structure was characterized by scanning electron microscopy (SEM). Cu foam was utilized as working electrode in three-electrode electrochemical system. Cyclic voltammetry (CV) scanning results exhibited the oxidation procedure of sucrose on Cu foam electrode. Amperometric i t scanning results indicated that Cu foam electrode selectively responded to sucrose from four tastant mixtures with low limit of detection (LOD) of 35.34 MUM, 49.85 MUM, 45.89 MUM, and 26.81 MUM, respectively. The existence of quinine, NaCl, citric acid (CA) and their mixtures had no effect on sucrose detection. Furthermore, mixtures containing different tastants could be discriminated by non linear double-layered cascaded series stochastic resonance (DCSSR) output signal to-noise ratio (SNR) eigen peak parameters of CV measurement data. The proposed method provides a promising way for sweetener analysis of commercial food. PMID- 26675855 TI - Effects of Grapevine Leafroll associated Virus 3 (GLRaV-3) and duration of infection on fruit composition and wine chemical profile of Vitis vinifera L. cv. Sauvignon blanc. AB - In order to determine the effects of Grapevine Leafroll associated Virus 3 (GLRaV 3) on fruit composition and chemical profile of juice and wine from Vitis vinifera L. cv. Sauvignon blanc grown in New Zealand, composition variables were measured on fruit from vines either infected with GLRaV-3 (established or recent infections) or uninfected vines. Physiological ripeness (20.4 degrees Brix) was the criterion established to determine the harvest date for each of the three treatments. Date of grape ripeness was strongly affected by virus infection. In juice and wine, GLRaV-3 infection prior to 2008 reduced titratable acidity compared with the uninfected control. Differences observed in amino acids from the three infection status groups did not modify basic wine chemical properties. In conclusion, GLRaV-3 infection slowed grape ripening, but at equivalent ripeness to result in minimal effects on the juice and wine chemistry. Time of infection produced differences in specific plant physiological variables. PMID- 26675856 TI - Influence of high-molecular-weight glutenin subunit composition at Glu-B1 locus on secondary and micro structures of gluten in wheat (Triticum aestivum L.). AB - Glutenin is one of the critical gluten proteins that affect the processing quality of wheat dough. High-molecular-weight glutenin subunits (HMW-GS) affect rheological behavior of wheat dough. This research demonstrated the effects of four variations of HMW-GS composition at the Glu-B1 locus on secondary and micro structures of gluten and rheological properties of wheat dough, using the bread wheat Xinong 1330 and its three near-isogenic lines (NILs). Results indicated that the Amide I bands of the four wheat lines shifted slightly, but the secondary structure, such as content of alpha-helices, beta-sheets, disulfide bands, tryptophan bands and tyrosine bands, differed significantly among the four NILs. The micro structure of gluten in NIL 2 (Bx14+By15) and NIL 3 (Bx17+By18) showed more cross linkage, with two contrasting patterns. Correlation analysis demonstrated that the content of beta-sheets and disulfide bonds has a significant relationship with dough stability, which suggests that the secondary structures could be used as predictors of wheat quality. PMID- 26675857 TI - Nondestructive quantifying total volatile basic nitrogen (TVB-N) content in chicken using hyperspectral imaging (HSI) technique combined with different data dimension reduction algorithms. AB - Hyperspectral imaging (HSI) system has been used to assess the chicken quality in this work. Principle component analysis (PCA) and Ant Colony Optimization (ACO) were comparatively used for data dimension reduction. First, we selected 5 dominant wavelength images from chicken hypercube using PCA and ACO. Then, 6 textural variables based on statistical moments were extracted from each dominant wavelength image, thus totaling to 30 variables. Next, we selected the classic back propagation artificial neural network (BPANN) algorithm for modeling. Experimental results showed the performance of ACO-BPANN model is superior to that of PCA-BPANN model, and the optimum ACO-BPANN model was achieved with RMSEP=6.3834 mg/100g and R=0.7542 in the prediction set. Our work implies that HSI integrating spectral and spatial information has a high potential in quantifying TVB-N content of chicken in rapid and non-destructive manner, and ACO has superiority in dimension reduction of hypercube. PMID- 26675858 TI - Determination of phthalate esters in teas and tea infusions by gas chromatography mass spectrometry. AB - Phthalate esters (PAEs), a group of environmental pollutants which are carcinogenic to human body, have been detected in teas. In this work, five PAEs in teas and tea infusions were quantitatively determined by a modified simultaneous distillation extraction (SDE) coupled with gas chromatography-mass spectrometry. After the optimization of SDE, the proposed method afforded a wide range of linearity and high linear regression coefficients with the limits of detection range of 0.24-3.72 MUg/kg. The average recoveries were 79.83-116.67% for tea samples and 78.22-101.64% for tea infusions with all the relative standard deviations below 20%. The total content of five PAEs in teas was 1.135 3.734 mg/kg and the total dissolving ratio of five PAEs from tea to infusion was 19.05-28.07% for the selected tea samples. The risk assessment result of all the selected tea samples demonstrated that the population with the habit of drinking tea won't cause risk to human health. PMID- 26675859 TI - Rapid and non-destructive determination of quality parameters in the 'Tommy Atkins' mango using a novel handheld near infrared spectrometer. AB - The objective of this study was to evaluate the potential of a new handheld ultra compact near infrared (NIR) spectrometer, based on the linear-variable filter (LVF) technology for rapid and non-destructive quality control analysis of the 'Tommy Atkins' mango. Multivariate calibration models were built using the Partial Least Squares (PLS) regression method to determine soluble solids (SS), dry matter (DM), titratable acidity (TA) and pulp firmness (PF). Different spectral pre-processing techniques were tested. Coefficient of determination and root mean square errors of prediction (RMSEP) values were, respectively: 0.92 and 0.55 degrees Brix for SS, 0.67 and 0.51% for DM, 0.50 and 0.17% citric acid for TA, 0.72 and 12.2N for PF. The predictive models allowed monitoring physico chemical changes in each fruit during ripening. The results show the feasibility of using the new NIR handheld spectrometer to determine quality parameters in the 'Tommy Atkins' mango. PMID- 26675860 TI - A novel process for preparing low-fat peanuts: Optimization of the oil extraction yield with limited structural and organoleptic damage. AB - The main purpose of this study was to extract the maximum amount of oil from peanuts without causing major damage and preserving their organoleptic quality after defatting. Accordingly, a successful, healthy, eco-friendly and economic defatting process for peanuts was implemented using mechanical oil expression, which was optimized by means of Response Surface Methodology. The results demonstrated that maximum extraction yields were obtained at a low initial moisture content (5-7% d.b.). Defatting and deformation ratios were mostly affected by the pressure and water content with high correlation coefficients (98.4% and 97.5%, respectively), and overall acceptability decreased following higher oil extraction yields. It was concluded that the optimum values for the product moisture content, pressure, and pressing duration were 5% d.b., 9.7 MPa and 4 min, respectively, with a defatting ratio of 70.6%. This resulted in an insignificant irreversible deformation ratio (<1%) and an overall acceptability of 7.6 over 10. PMID- 26675861 TI - An efficient method for high-purity anthocyanin isomers isolation from wild blueberries and their radical scavenging activity. AB - An efficient process for the purification of anthocyanin monomeric isomers from wild blueberries of Lake Saint-Jean region (Quebec, Canada) was developed and easy scalable at industrial purpose. The blueberries were soaked in acidified ethanol, filtered, and the filtrate was cleaned by solid phase extraction using silica gel C-18 and DSC-SCX cation-exchange resin. Anthocyanin-enriched elutes (87 wt.%) were successfully fractionated by preparative liquid chromatography. The major anthocyanins mono-galactoside, -glucoside and -arabinoside isomers of delphinidin, cyanidin, petunidin, peonidin and malvidin were isolated with a purity up to 100% according to their LC-MS and (1)H NMR spectra. The oxygen radical absorbance capacity (ORAC) of the obtained pure anthocyanins was evaluated. Delphinidin-3-galactoside has the highest capacity (13.062 +/- 2.729 MUmol TE/MUmol), and malvidin-3-glucoside the lowest (0.851 +/- 0.032 MUmol TE/MUmol). A mechanistic pathway preview is suggested for the anthocyanins scavenging free radical activity by hydrogen transfer. PMID- 26675862 TI - Water electrolyte promoted oxidation of functional thiol groups. AB - The formation of disulfide bonds is of the utmost importance for a wide range of food products with gluten or globular proteins as functional agents. Here, the impact of mineral electrolyte composition of aqueous solutions on thiol oxidation kinetics was studied, using glutathione (GSH) and cysteine (CYS) as model systems. Interestingly, the oxidation rate of both compounds into their corresponding disulfides was significantly higher in common tap water than in ultrapure water. The systematic study of different electrolyte components showed that especially CaCl2 improved the oxidation rate of GSH. However, this effect was not observed for CYS, which indicated a strong impact of the local chemical environment on thiol oxidation kinetics. PMID- 26675863 TI - Mass spectrometry detection of fraudulent use of cow whey in water buffalo, sheep, or goat Italian ricotta cheese. AB - Ricotta cheese is a typical Italian product, made with whey from various species, including cow, buffalo, sheep, and goat. Ricotta cheese nominally manufactured from the last three species may be fraudulently produced using the comparatively cheaper cow whey. Exposing such food frauds requires a reliable analytical method. Despite the extensive similarities shared by whey proteins of the four species, a mass spectrometry-based analytical method was developed that exploits three species-specific peptides derived from beta-lactoglobulin and alpha lactalbumin. This method can detect as little as 0.5% bovine whey in ricotta cheese from the other three species. Furthermore, a tight correlation was found (R(2)>0.99) between cow whey percentages and mass spectrometry measurements throughout the 1-50% range. Thus, this method can be used for forensic detection of ricotta cheese adulteration and, if properly validated, to provide quantitative evaluations. PMID- 26675864 TI - Determination of 18 water-soluble artificial dyes by LC-MS in selected matrices. AB - A multi-residue method based on two different extraction procedures was developed and compared with liquid chromatography electrospray ionization tandem mass spectrometry analysis of eighteen water-soluble artificial colours including Tartrazine (E102), Chrysoine (E103), Quinoline Yellow (E104), Yellow 2G (E107), Sunset Yellow (E110), Azorubine (E122), Amaranth (E123), Ponceau 4R (E124), Erythrosine (E127), Red 2G (E128), Allura Red (E129), Patent Blue V (E131), Indigo Carmine (E132), Brilliant Blue (E133), Green S (E142), Fast Green (E143), Brilliant Black (E151), and Black 7984 (E152) in sugar and gummy confectionary, ice-cream, and chocolate sweets. Sample preparation included SPE clean-up and liquid-liquid extraction for ice-cream and chocolate sweets. Accuracy was evaluated by recovery experiments. Correlation between response and concentration was obtained with R(2)>0.98 for all but six colours. Limits of quantification were within the 10-50 MUg/kg range for E129; 20-200 MUg/kg for E152; 10-250 MUg/kg for E103; 10-500 MUg/kg for E102, E104, E107, E110, E122, E123, E124, E127, E128, E131, E133; 20-800 MUg/kg for E132, 142, 151; and 10-1000 MUg/kg for E143. CV for repeatability ranged from 4.0% to 51.0%, while the CV for intermediate reproducibility ranged from 5.8% to 41.4%. Finally, recoveries varied from 84.3% to 166.0%. Together, these demonstrate that the method has been validated for complex matrices and is, thus, fit-for-purpose. PMID- 26675865 TI - Influence of fat and phytosterols concentration in margarines on their degradation at high temperature. A study by (1)H Nuclear Magnetic Resonance. AB - The objective of this work was to study the influence of several factors, especially fat and phytosterols concentration, on the behavior of margarine under thermo-oxidative conditions. For this purpose, margarines with similar compositions in acyl groups, but differing in the concentration of both fat and phytosterols, were heated at 180 degrees C. The changes in the main components of margarine lipids and the formation of new compounds throughout the thermal treatment were monitored by (1)H Nuclear Magnetic Resonance. The results show that the presence of high concentrations of phytosterols seems to have an antioxidant effect, since it slows down the thermo-oxidation rate of margarine and, consequently, the generation rate and concentrations of secondary oxidation products such as some aldehydes, epoxides and alcohols. The oil-water ratio also seems to have an important effect on margarine behavior, in such a way that the lower the fat concentration is, the higher its thermo-oxidation rate. PMID- 26675866 TI - Domestic cooking methods affect the phytochemical composition and antioxidant activity of purple-fleshed potatoes. AB - The effects of domestic cooking methods (boiling, baking, steaming, microwaving, frying, and stir-frying) and a new cooking method (air-frying) on the composition of phytochemicals (phenolics, anthocyanins, and carotenoids) and the antioxidant activity in purple-fleshed potatoes were investigated. Compared with raw potatoes, reductions of 23.59-90.42%, 7.09-72.44%, 7.45-83.15%, and 20.15-76.16% in the vitamin C, total phenolic, anthocyanin and carotenoid contents, respectively, was observed after cooking. Decreases of 7.88%, 21.55%, 22.48, 6.31%, and 61.38% in DPPH radical-scavenging activity was also observed after boiling, steaming, baking, microwaving and stir-frying, respectively, whereas an increase of 30.52% was noted after air-frying. A correlation analysis revealed that the antioxidant activity was in accordance with the total phenolic content and that this activity showed the lowest correlation with the vitamin C content. Among all of the cooking methods investigated in this study, stir-frying retained only slight levels of the phytochemicals and antioxidant activity observed in raw potatoes, whereas steaming and microwaving were able to retain most of the health promoting compounds found in raw potatoes and may thus be suitable methods for cooking potatoes. PMID- 26675867 TI - Occurrence of deoxynivalenol in wheat, Hebei Province, China. AB - Analysis of deoxynivalenol (DON) and its metabolites 3-acetyl and 15 acetyldeoxynivalenol (3-ADON and 15-ADON) in wheat flour samples by liquid chromatography-tandem mass spectrometry (LC/MS/MS) during 2011-2013 was conducted. [(13)C15]-DON was used as the internal standard to accomplish as accurate as possible quantitation. Of all wheat samples (n=672), 91.5% were positive for DON, at levels ranging from 2.4 to 1130 MUg/kg, with a median value of 154 MUg/kg. The DON derivatives (3-Ac-DON, 15-Ac-DON) were far less frequently found and at lower levels than DON. The probable daily intakes (PDI) of DON (0.49 in 2011; 0.86 in 2012; 0.56 in 2013, expressed as MUg/kg body weight/day) were all within the PDI of 1.0 MUg/kg of bw/day for DON set by Scientific Committee for Food (SCF) in 2002. Still, persistent monitoring of DON is important. PMID- 26675868 TI - Iron binding efficiency of polyphenols: Comparison of effect of ascorbic acid and ethylenediaminetetraacetic acid on catechol and galloyl groups. AB - Dietary polyphenols are markedly studied for their antioxidant activity. They also have a negative impact on nutrition whereby they interfere with iron absorption. Common dietary polyphenols include: catechins, flavonols, flavanols, flavones, anthocyanins, proanthocyanidins and phenolic acids. Ascorbic acid (AA) and Ethylenediaminetetraacetic acid (EDTA) are commonly used to counter act this reaction and increase iron bioavailability. This study was aimed at determining the effect of AA and EDTA on the catechol or galloyl iron binding ability of pure phenolics, coffee and tea. Phenolic concentrations of 40, 80, 610, 240, 320, 400, 520 and 900 MUg/ml were tested against six levels of AA and EDTA. These effects were studied in detail using Multivariate Analysis of Variance (MANOVA) with the hypothesis that there would be one or more mean differences between the ratio of enhancer and the different concentrations of samples tested. AA was found to be more efficient than EDTA in a way that lesser quantity is required for completely overcoming negative iron binding effects of polyphenols and similar samples. PMID- 26675869 TI - Stabilization of betalains: A review. AB - Betalains are vacuolar pigments composed of a nitrogenous core structure, betalamic acid [4-(2-oxoethylidene)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid]. This compound consists of a chromophore substructure 1,7-diazaheptamethin. Betalamic acid condenses with imino compounds (cyclo-DOPA or its glucosyl derivatives), or amines and/or their derivatives to form a variety of betacyanins (violet) and betaxanthins (yellow), respectively. These pigments exhibit absorption maxima in between 532-550 nm and 457-485 nm, respectively. These colors are currently in use as food additives as they are bioactive and completely safe to consume. However, owing to poor stability, their potential application in pharmaceuticals and cosmetics is severely compromised. There is a lack of scientific reports highlighting their superior tinctorial strength including fluorescence, and their excellent water solubility. For widening the color spectrum and their usage, various betalain-rich extracts have been reviewed here, focusing on their matrix effects on stability vis-a-vis purified pigments of different structural make-up. This review also encompasses work carried out in the past related to stability/stabilization of betalains and future research direction for the same. PMID- 26675870 TI - Peanut proteins in periodate specific anion sensing: An ensuing reduction in allergic response. AB - Peanut proteins conarachin II, conarachin I and arachin were found to behave as highly selective fluorescence sensors for periodate amongst a set of different anions. The interactions of the proteins with periodate were also confirmed by other spectral methods and enzyme linked immunosorbent assay (ELISA). The results indicate a selective interaction of peanut proteins with periodate amongst chloride, sulphate, iodide, phosphate, nitrate, nitrite, bromide, fluoride, persulphate, acetate, thiosulphate, arsenite, arsenate, sulphite, and iodide. Periodate sensing using different synthesized organic molecules are already reported in the literature. In this article we report the efficiency of peanut proteins as anion sensor which are bioactive and inexpensive too. The protein periodate interactions have also resulted in a simultaneous reduction in allergenicity of the peanut proteins. A change in the secondary structure of the protein was found responsible for this change which was further established with the help of circular dichroism and Raman spectroscopy. PMID- 26675871 TI - Comparison of different drying methods on Chinese ginger (Zingiber officinale Roscoe): Changes in volatiles, chemical profile, antioxidant properties, and microstructure. AB - Nowadays, food industry is facing challenges in preserving better quality of fruit and vegetable products after processing. Recently, many attentions have been drawn to ginger rhizome processing due to its numerous health promoting properties. In our study, ginger rhizome slices were subjected to air-drying (AD), freeze drying (FD), infrared drying (IR), microwave drying (MD) and intermittent microwave & convective drying (IM&CD). Quality attributes of the dried samples were compared in terms of volatile compounds, 6, 8, 10-gingerols, 6 shogaol, antioxidant activities and microstructure. Results showed that AD and IR were good drying methods to preserve volatiles. FD, IR and IM&CD led to higher retention of gingerols, TPC, TFC and better antioxidant activities. However, FD and IR had relative high energy consumption and drying time. Therefore, considering about the quality retention and energy consumption, IM&CD would be very promising for thermo sensitive material. PMID- 26675872 TI - Effect of the intensity of cooking methods on the nutritional and physical properties of potato tubers. AB - The different intensities of common culinary techniques (boiling, baking and microwaving) produce several changes that reduce the nutritional and physical properties of potatoes. This study evaluated the effect of those cooking methods on the quality of commercial potato tubers (Agata, Kennebec, Caesar and Red Pontiac). The higher weight losses were obtained for baking, but the potato softening depended on the cultivar. Color losses were independent of the intensity of the treatment; however, microwaving promoted a prompt starch gelatinization with respect to the other methods. The resistant starch retention of baking and microwaving was higher than that of boiling, and the maximum retention of bioactive compounds was obtained with the lower core temperature during boiling, as well as higher temperature and shorter baking time and the lower power and longer microwaving time. Principal component analysis revealed significant relationships between the instrumental and functional properties of cooked potatoes. PMID- 26675873 TI - Quantification of peptides released during in vitro digestion of cooked meat. AB - We aimed to identify and quantify the peptides generated during in vitro digestion of cooked meat by liquid chromatography coupled with high resolution mass spectrometer. A total of 940 non-redundant peptides in the gastric compartment and 989 non-redundant peptides in the intestinal compartment were quantified and identified. Among the 71 different proteins identified, 43 meat proteins were found in the two digestive compartments, 20 proteins were specific to the gastric compartment and 8 proteins to the intestinal compartment. In terms of estimation, the proteins involved in muscle contraction and structure were preferentially enzymatically hydrolyzed in the small intestine. The effect of cooking provided different but less clear patterns of digestion. To the best of our knowledge, this constitutes the highest number of peptides identified in beef meat digests and provides a comprehensive database for meat protein digestion associated with cooking conditions. Such quantitative and qualitative differences may have important nutritional consequences. PMID- 26675874 TI - Lipid oxidation induced oxidative degradation of cereal beta-glucan. AB - In food systems, lipid oxidation can cause oxidation of other molecules. This research for the first time investigated oxidative degradation of beta-glucan induced by lipid oxidation using an oil-in-water emulsion system which simulated a multi-phased aqueous food system containing oil and beta-glucan. Lipid oxidation was monitored using peroxide value and hexanal production while beta glucan degradation was evaluated by viscosity and molecular weight measurements. The study showed that while lipid oxidation proceeded, beta-glucan degradation occurred. Emulsions containing beta-glucan, oil and ferrous ion showed significant viscosity and molecular weight decrease after 1 week of oxidation at room temperature. Elevated temperature (40 degrees C) enhanced the oxidation reactions causing higher viscosity drop. In addition, the presence of beta-glucan appeared to retard the hexanal production in lipid oxidation. The study revealed that lipid oxidation may induce the degradation of beta-glucan in aqueous food systems where beta-glucan and lipids co-exist. PMID- 26675875 TI - Studying the effect of storage conditions on the metabolite content of red wine using HILIC LC-MS based metabolomics. AB - The main aim of this work was to develop an untargeted normal phase LC-MS method, starting from a targeted method already validated for the analysis of 135 polar metabolites. Since the LC instrument and column were the same, most of the chromatographic conditions remained identical, while the adaptations focused on maintaining the ionic strength of the eluents constant. The sample preparation was simplified and the effectiveness of LC-MS for long batches was evaluated, in order to record the maximum number of metabolites with good chromatographic resolution and the best MS stability and accuracy. The method was applied to study the influence of storage conditions on wine composition. Slightly sub optimum storage conditions had a major impact on the polar metabolite fingerprint of the red wines analysed and the markers revealed included phenolics, vitamins and metabolites indentified in wine for the first time (4-amino-heptanedioic acid and its ethyl ester). PMID- 26675876 TI - Green biorefinery - Industrial implementation. AB - Oil refineries currently generate a multitude of products for almost every sphere of life at very high efficiency. However, fossil raw materials are just available in limited quantities. The development of comparable BIOREFINERIES is necessary to make a variety of competitive biological products regarding their equivalent products based on fossil raw materials. The product range of a biorefinery comprises products that can be manufactured on the basis of crude oil, as well as such products that cannot be produced on the basis of crude oil (Kamm, Gruber, & Kamm, 2011). GREEN BIOREFINERIES [GBR's] are complex systems of sustainable, environment- and resource-friendly technologies for a comprehensive material and energy use or recovery of renewable raw materials in form of green and waste biomasses from a sustainable land use as target (Kamm et al., 2009; Digman, Runge, Shinners, & Hatfield, 2013). PMID- 26675877 TI - A Rare Case of Intra- Abdominal Bronchogenic Cyst- A Case Report. AB - Bronchogenic cysts are developmental foregut anomalies usually located in the mediastinum. A 90% of the bronchogenic cysts occur in the posterior aspect of superior mediastinum. Retroperitoneal location of a bronchogenic cyst is rare. We report a rare case of intra abdominal bronchogenic cyst. A CT scan was done for a 34-year-old female who presented with complains of heaviness in the right flank. CT scan revealed a large cyst of 10 x 6 cm in the right hypochondrium. Cyst was removed laparoscopically and the histopathology revealed a bronchogenic cyst. PMID- 26675878 TI - Expression of Osteopontin in Oral Squamous Cell Carcinoma and its Surgical Margins-An Immunohistochemical Study. AB - INTRODUCTION: Despite the advances in the treatment modalities offered for oral squamous cell carcinoma. The recurrence rate of it still remains quite high. Early detection of recurrence will improve the outcome and the survival of the patient. Osteopontin, a transformation-related phosphorylated protein in epithelial cells has been closely related with tumourigenesis. This study was undertaken to explore the potential of OPN as a tumour marker of recurrence in OSCC. AIM: To analyse the expression of Osteopontin (OPN) in Oral Squamous Cell Carcinoma (OSCC), patient matched tumour free surgical margins and normal oral mucosa and to correlate with local & loco regional recurrence. MATERIALS AND METHODS: Twenty cases each of formalin fixed paraffin embedded blocks of histopathologically diagnosed cases of OSCC, patient matched tumour free surgical margins and normal oral mucosal tissues were obtained from the archives of the Oral Pathology & Microbiology Department, Faculty of Dental Sciences, SRU and Govt. Arignar Anna Memorial Cancer Hospital, Kancheepuram. Immunohistochemical analysis was performed with an antibody to Osteopontin protein. Patients with secondary tumours and those treated with chemotherapy and radiotherapy were excluded from this study. RESULTS: The expression of OPN was elevated in 95% of tumours & 55% of histologically tumour free margin samples. There was negative OPN expression in normal mucosal samples. The result of the study was statistically analysed using Pearson chi-square test and was found to be statistically significant. CONCLUSION: OPN can be used as a diagnostic marker in Oral Squamous Cell Carcinoma. In the tumour free surgical margins, elevated levels of OPN may predict a significantly increased risk of recurrence. PMID- 26675879 TI - Speed versus accuracy in visual search: Optimal performance and neural architecture. AB - Searching for objects among clutter is a key ability of the visual system. Speed and accuracy are the crucial performance criteria. How can the brain trade off these competing quantities for optimal performance in different tasks? Can a network of spiking neurons carry out such computations, and what is its architecture? We propose a new model that takes input from V1-type orientation selective spiking neurons and detects a target in the shortest time that is compatible with a given acceptable error rate. Subject to the assumption that the output of the primary visual cortex comprises Poisson neurons with known properties, our model is an ideal observer. The model has only five free parameters: the signal-to-noise ratio in a hypercolumn, the costs of false-alarm and false-reject errors versus the cost of time, and two parameters accounting for nonperceptual delays. Our model postulates two gain-control mechanisms--one local to hypercolumns and one global to the visual field--to handle variable scene complexity. Error rate and response time predictions match psychophysics data as we vary stimulus discriminability, scene complexity, and the uncertainty associated with each of these quantities. A five-layer spiking network closely approximates the optimal model, suggesting that known cortical mechanisms are sufficient for implementing visual search efficiently. PMID- 26675880 TI - Contour integration, attentional cuing, and conscious awareness: An investigation on the processing of collinear and orthogonal contours. AB - Previous literature suggests that low-level stimulus properties determine the detection performance of contours and are used to define different contour types. Here we investigated the processing of different types of contours under conscious and unconscious conditions. In Experiment 1, we adopted an inattentional blindness paradigm and showed that collinear contours (i.e., a contour type that is frequently observed in natural images) induced a positive cuing effect in both the conscious and unconscious conditions, whereas orthogonal contours (which are less prevalent in the natural environment) attracted attention only when consciously perceived. In Experiment 2, we showed that collinear contours rendered invisible by continuous flash suppression emerged from suppression more rapidly than a random field, whereas orthogonal contours had no such breaking superiority. These results suggest that collinear but not orthogonal contours can be processed and serve as attentional cues without conscious awareness. Our findings provide further evidence that the relevance of the contours to natural statistics could be a key evolutionary factor that decides whether a contour can be unconsciously processed to increase its detectability in a clutter environment. PMID- 26675881 TI - Characterizing visual asymmetries in contrast perception using shaded stimuli. AB - Previous research has shown a visual asymmetry in shaded stimuli where the perceived contrast depended on the polarity of their dark and light areas (Chacon, 2004). In particular, circles filled out with a top-dark luminance ramp were perceived with higher contrast than top-light ones although both types of stimuli had the same physical contrast. Here, using shaded stimuli, we conducted four experiments in order to find out if the perceived contrast depends on: (a) the contrast level, (b) the type of shading (continuous vs. discrete) and its degree of perceived three-dimensionality, (c) the orientation of the shading, and (d) the sign of the perceived contrast alterations. In all experiments the observers' tasks were to equate the perceived contrast of two sets of elements (usually shaded with opposite luminance polarity), in order to determine the subjective equality point. Results showed that (a) there is a strong difference in perceived contrast between circles filled out with luminance ramp top-dark and top-light that is similar for different contrast levels; (b) we also found asymmetries in contrast perception with different shaded stimuli, and this asymmetry was not related with the perceived three-dimensionality but with the type of shading, being greater for continuous-shading stimuli; PMID- 26675882 TI - An overview of the contribution of dairy and cheese intakes to nutrient intakes in the Irish diet: results from the National Adult Nutrition Survey. AB - Dairy products are important contributors to nutrient intakes. However, dairy intakes are reportedly declining in developed populations, potentially due to concerns regarding Na and SFA in dairy foods, particularly cheese. This could impact other nutrient intakes. The present study used data from the National Adult Nutrition Survey (NANS) to (1) examine dairy intakes, with a specific focus on cheese, and (2) to examine the contribution of cheese to population nutrient intakes. The NANS captured detailed dietary intake data from a nationally representative sample (n 1500) between 2008 and 2010 using 4-d semi-weighed food diaries; 99.9% of the population reported dairy intake. Mean daily population dairy intake was 290.0 (SD 202.1) g. Dairy products provided 8.7% of the population intake of reported dietary Na, 19.8% SFA, 39% Ca, 34.5% vitamin B12 and 10.5% Mg. Cheese alone provided 3.9% Na intake, 9.1% Ca, 12.6% retinol, 8.3% SFA, 3.7% protein, 3.4% vitamin B12 and 3.2% riboflavin. High dairy consumers had greater Ca and Mg intakes per 10 MJ, greater total energy intake, greater percentage of energy from carbohydrate and SFA and lower Na intakes compared with low dairy consumers. Similar trends were observed for high consumers of cheese for most nutrients except Na. These results demonstrate that dairy and cheese are important contributors to nutrient intakes of public health interest, such as Ca and B12. Our analysis also demonstrated that food-based dietary guidelines recommending lower-fat versions of dairy products are warranted. PMID- 26675884 TI - NMR spectroscopy and DFT calculations of a self-assembled arene ruthenium rectangle obtained from a combination of coordination and hydrogen bonds. AB - The hydrogen-bonded arene ruthenium metalla-rectangle, [(p cymene)2Ru2(OO?OO)(UPy)2]2(4+), obtained from 1-(4-oxo-6-undecyl-1,4 dihydropyrimidin-2-yl)-3-(pyridin-4-ylmethyl)urea (UPy) and the dinuclear arene ruthenium clip (p-cymene)2Ru2(OO?OO)Cl2 (OO?OO = 2,5-dioxido-1,4-benzoquinonato), is investigated by means of solution-phase NMR spectroscopy. Rotating frame nuclear Overhauser effect measurements are used to probe the H-bond network that drives the UPy self-assembly as well as the full rectangular supramolecular system. An effective distance that takes into account both intra- and intermolecular polarization-transfer pathways is utilised for data analysis. The experimental findings are corroborated by DFT calculations of NMR parameters and internuclear distances, thus confirming the formation of a very stable tetranuclear metalla-assembly. PMID- 26675885 TI - Neuro-oncology family caregiving: review and directions for future research. AB - Vast research has underscored negative psychological and physical effects of providing care for someone with a chronic illness. Unfortunately, caregivers of persons with a primary malignant brain tumor have received very little attention in the research literature. The purpose of this article is to review what is known regarding descriptive and interventional work in neuro-oncology caregiving and to suggest avenues for future research. A total of 36 descriptive and six intervention studies were identified for this review. Increased distress in neuro oncology caregivers has been linked to younger age; higher levels of economic burden and unmet needs; and lower levels of social support, spirituality and caregiver mastery. Intervention research suggests that educational programs and cognitive behavioral therapy may decrease neuro-oncology caregiver distress. PMID- 26675886 TI - Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4 methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-beta1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF. PMID- 26675887 TI - The dopamine D1 receptor agonist SKF-82958 effectively increases eye blinking count in common marmosets. AB - Eye blinking is a spontaneous behavior observed in all mammals, and has been used as a well-established clinical indicator for dopamine production in neuropsychiatric disorders, including Parkinson's disease and Tourette syndrome [1,2]. Pharmacological studies in humans and non-human primates have shown that dopamine agonists/antagonists increase/decrease eye blinking rate. Common marmosets (Callithrix jacchus) have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field due to their more developed prefrontal cortex than rodents, easy handling compare to other non human primates, and requirement for small amounts of test drugs. In this study, we evaluated the effects of dopamine D1-4 receptors agonists on eye blinking in common marmosets. Our results show that the dopamine D1 receptor agonist SKF 82958 and the non-selective dopamine receptor agonist apomorphine significantly increased common marmosets eye blinking count, whereas the dopamine D2 agonist (+)-PHNO and the dopamine D3 receptor agonist (+)-PD-128907 produced somnolence in common marmosets resulting in a decrease in eye blinking count. The dopamine D4 receptor agonists PD-168077 and A-41297 had no effect on common marmosets' eye blinking count. Finally, the dopamine D1 receptor antagonist SCH 39166 completely blocked apomorphine-induced increase in eye blinking count. These results indicate that eye blinking in common marmosets may be a useful tool for in vivo screening of novel dopamine D1 receptor agonists as antipsychotics. PMID- 26675888 TI - Helium preconditioning protects against neonatal hypoxia-ischemia via nitric oxide mediated up-regulation of antioxidases in a rat model. AB - This study aimed to investigate the role of nitric oxide (NO) in the neuroprotective effects of helium preconditioning (He-PC) in a neonatal hypoxia/ischemia (HI) rat model. Seven-day old rat pups were divided into normal control group, He-PC group, HI group, He-PC+HI group, L-NAME+HI group and L NAME+He-PC+HI group. HI was induced by exposure to 80% oxygen for 90 min. He-PC was conducted with 70% helium-30% oxygen for three 5-min periods. Three hours after He-PC, animals in control group and He-PC group were sacrificed, and the brain was collected for the detection of NO content. At 24h after HI, animals in control group, HI group, He-PC+HI group, and L-NAME+He-PC+HI group were sacrificed, and the brain was collected for detection of infarct ratio, antioxidases (SOD, HO-1 and Nrf2), DNA binding activity of Nrf2 and TUNEL staining. Three weeks later, the neurological function and brain atrophy were determined. Results showed pretreatment with L-NAME alone failed to exert protective effect on HI. He-PC significantly increased NO content, reduced the brain infarct area, increased anti-oxidases expression and DNA binding activity of Nrf2, decreased the apoptotic cells, and improved the neurological function and brain atrophy. In addition, this protection was markedly inhibited by L-NAME (a non-selective NOS inhibitor). These findings suggest that the He-PC may induce NO production to activate Nrf2, exerting neuroprotective effect on neonatal HI. PMID- 26675889 TI - Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats. AB - Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation. PMID- 26675890 TI - Superhydrophobic magnetic poly(DOPAm-co-PFOEA)/Fe3O4/cellulose microspheres for stable liquid marbles. AB - Novel magnetic superhydrophobic cellulose-based microspheres were fabricated using poly(DOPAm-co-PFOEA), which provide remarkable stability to liquid marbles with various liquids for liquid droplet transportation and manipulation. PMID- 26675891 TI - Spatially transformed fluorescence image data for ERK-MAPK and selected proteins within human epidermis. AB - BACKGROUND: Phosphoprotein signalling pathways have been intensively studied in vitro, yet their role in regulating tissue homeostasis is not fully understood. In the skin, interfollicular keratinocytes differentiate over approximately 2 weeks as they traverse the epidermis. The extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) pathway has been implicated in this process. Therefore, we examined ERK-MAPK activity within human epidermal keratinocytes in situ. FINDINGS: We used confocal microscopy and immunofluorescence labelling to measure the relative abundances of Raf-1, MEK1/2 and ERK1/2, and their phosphorylated (active) forms within three human skin samples. Additionally, we measured the abundance of selected proteins thought to modulate ERK-MAPK activity, including calmodulin, beta1 integrin and stratifin (14-3-3sigma); and of transcription factors known to act as effectors of ERK1/2, including the AP-1 components Jun-B, Fra2 and c-Fos. Imaging was performed with sufficient resolution to identify the plasma membrane, cytoplasm and nucleus as distinct domains within cells across the epidermis. The image field of view was also sufficiently large to capture the entire epidermis in cross-section, and thus the full range of keratinocyte differentiation in a single observation. Image processing methods were developed to quantify image data for mathematical and statistical analysis. Here, we provide raw image data and processed outputs. CONCLUSIONS: These data indicate coordinated changes in ERK-MAPK signalling activity throughout the depth of the epidermis, with changes in relative phosphorylation-mediated signalling activity occurring along the gradient of cellular differentiation. We believe these data provide unique information about intracellular signalling as they are obtained from a homeostatic human tissue, and they might be useful for investigating intercellular heterogeneity. PMID- 26675892 TI - Preferential acquisition and inoculation of PVYNTN over PVYO in potato by the green peach aphid Myzus persicae (Sulzer). AB - In the past decade, the incidence and distribution of the recombinant, tuber necrotic strain of Potato virus Y (PVYNTN) has been increasing in the US seed potato crop while the ordinary strain (PVYO) has been decreasing. The transmission efficiency of both strains was determined from two potato cultivars when acquired sequentially by the same aphid or when acquired by separate aphids and inoculated to the same plant. PVYNTN was transmitted more efficiently than PVYO and the order of acquisition or inoculation did not affect the preferential transmission of PVYNTN. When a recipient plant became infected with both strains, PVYNTN maintained higher titre than PVYO and would facilitate the acquisition of PVYNTN. Furthermore, the acquisition and transmission of PVYNTN over PVYO was enhanced in the potato cultivar that expressed a strain-specific Ny-like resistance gene that confers partial resistance to PVYO. PMID- 26675893 TI - Risk Factor Analysis in Clinical Isolates of ESBL and MBL (Including NDM-1) Producing Escherichia coli and Klebsiella Species in a Tertiary Care Hospital. AB - BACKGROUND: Extended-spectrum beta-lactamase (ESBL) and metallo-beta-lactamase (MBL) producing Gram negative organisms are emerging as a worldwide public health concern. AIM: To elucidate risk factors for infection with ESBL and MBL (also NDM 1) producing E. coli and Klebsiella spp. MATERIALS AND METHODS: A prospective observational study was conducted from November 2010 to March 2012. ESBL production was detected using ESBL E-test, MBL by MBL E-test and NDM-1 by polymerase chain reaction (PCR). Risk factors analysed includes age, sex, clinical specimen, type of infection, duration of hospital stay prior to collection of sample, admitting ward, antimicrobial susceptibility, previous antibiotics used, co-morbid illnesses like diabetes mellitus, immunodeficiency, low birth weight, respiratory/neurological/cardiac/haematological/liver diseases, malignancy, urinary or central venous catheter, ventilatory support, surgical procedures and dialysis. STATISTICAL ANALYSIS: z-test or Fisher's exact test. RESULTS: E. coli - ESBL producing isolates E. coli revealed female preponderance, equal incidence of hospital and community acquired infections, mostly from surgical wards, isolated from urine, age group among females >20-30 years and among males >28 days-1 year. They showed high resistance to cephalosporins, monobactam, penicillin but low resistance to carbapenems and aminoglycosides. Co morbid conditions observed were surgery, urinary catheterisation, haematological disease, ventilatory support, diabetes mellitus and neurological disease. MBL producing strains were mainly from females, surgical wards, (including both NDM-1 isolates), hospital acquired infections, isolated from body fluids (NDM-1 positive), female genital tract specimen and urine (one NDM-1 positive). NDM-1 positive isolates belonged to age groups >5-10 year and >0-28 days and underwent surgery and urinary catheterisation. Klebsiella spp.- ESBL producing isolates showed female preponderance, hospital acquired infections, from surgical wards, high resistance levels to cephalosporins, fluoroquinolones, monobactam, but low levels to carbapenems, among males isolated from pus in age group >0-28 days and >28 days -1 year and among females from urine in >20-30 years, no significant difference when correlated with risk factors. MBL (NDM-1) producing isolates were mainly from females with age range 0 days to 70 years, mainly admitted to ICU/postoperative wards with urinary catheter in-situ, ventilatory support, surgery, diabetes mellitus, haematological and neurological disease. CONCLUSION: Risk factors for infections due to ESBL and MBL producing Gram Negative Bacteria (GNB) should be clearly identified to reduce their spread and to optimise antibiotic use. PMID- 26675895 TI - Role of virtual reality simulation in endoscopy training. AB - Recent advancements in virtual reality graphics and models have allowed virtual reality simulators to be incorporated into a variety of endoscopic training programmes. Use of virtual reality simulators in training programmes is thought to improve skill acquisition amongst trainees which is reflected in improved patient comfort and safety. Several studies have already been carried out to ascertain the impact that usage of virtual reality simulators may have upon trainee learning curves and how this may translate to patient comfort. This article reviews the available literature in this area of medical education which is particularly relevant to all parties involved in endoscopy training and curriculum development. Assessment of the available evidence for an optimal exposure time with virtual reality simulators and the long-term benefits of their use are also discussed. PMID- 26675894 TI - Ophthalmic indications of amniotic membrane transplantation in Mexico: an eight years Amniotic Membrane Bank experience. AB - Amniotic membrane, the inner layer of the placenta, has biological properties (e.g. promotes epithelization, reduces fibrosis, secretes antimicrobial products and inhibits immune responses) which make it a useful option for several ophthalmologic procedures, especially those involving the ocular surface. Its use in eye surgery has been reported by other authors. To our knowledge, there is a lack of descriptive studies on surgical indications using amniotic membrane in Mexican population. Here we describe the eight years Amniotic Membrane Bank experience in Mexico, including a detailed protocol of the donors selection, tissue harvesting, preparation, storage and distribution of amniotic membrane since its establishment in 2007. Moreover, we describe the Ophthalmological indications of amniotic membrane transplantation of the total of 1686 amniotic membranes fragments used during eight years. The five most common indications for amniotic membrane transplantation were pterygium (46 %), corneal ulcers (12.6 %), conjunctival surface repair (11.1 %), neoplasms (7.4 %), and persistent epithelial defects (7.3 %). In addition, we compared the indications of amniotic membrane use in two different types of Institutions: general hospitals and ophthalmologic reference hospitals. We found interesting differences between the indications and use rates between these institutions, although pterygium was the most frequent pathology that amniotic membrane fragments were used in both institutions, there was up to a five-fold increase in the use of amniotic membrane for correction of persistent epithelial defects in reference hospitals which could be explained due to the more complex and severe ophthalmological pathologies admitted in reference hospitals. In conclusion, Amniotic Membrane is used in a numerous ocular pathologies and especially on pterygium in our Mexican population. PMID- 26675896 TI - Overcoming challenges in the diagnosis and treatment of myasthenia gravis. AB - In recent years, the discovery of new autoantigens and the use of sensitive assays have expanded the clinical spectrum of myasthenia gravis (MG). In particular, antibodies binding to clustered acetylcholine receptors and to the low-density lipoprotein receptor-related protein 4 have not only bridged a significant gap in diagnosis but also have relevant clinical implications. MG management includes different therapeutic options, from symptomatic agents as the only therapy in mildly affected cases to combined long-term immunosuppression and thymectomy in patients with severe disabling disease. MG biological diversity can influence the response to therapies and should be taken into account when planning treatment. Biologic agents are promising, though their use is currently limited to patients with refractory disease. PMID- 26675897 TI - Hyporheic invertebrate assemblages at reach scale in a Neotropical stream in Brazil. AB - In the Neotropical Region, information concerning hyporheic communities is virtually non-existent. We carried out a sampling survey in the hyporheic zone of the Tijuca River, in the Tijuca National Park, located in the urban area of the city of Rio de Janeiro. Biological samples from the hyporheic zone were collected in three different stream reaches, in June 2012. The main objectives were: 1) to describe the structure of invertebrate assemblages in the hyporheic zone of a neotropical stream; 2) to apply a reach-scale approach in order to investigate spatial patterns of the hyporheic assemblages in relation to hydrology, depth and microhabitat typology. A total of 1460 individuals were collected and identified in 31 taxa belonging to Nematoda, Annelida, Crustacea, Hydrachnidia and Insecta. The class Insecta dominated the upper layer of the hyporheic zone. Copepods were the most abundant taxon among crustaceans and occurred mostly in the upwelling areas of the reaches. The results of this study represent one of the few contributions so far about hyporheic invertebrate assemblages of the Neotropical Region. PMID- 26675898 TI - First record of larvae of Hysterothylacium (Nematoda: Anisakidae) with zoonotic potential in the pirarucu Arapaima gigas (Osteichthyes: Arapaimidae) from South America. AB - Third-stage larvae (L3) of Hysterothylacium sp. were collected by the first time in juveniles of pirarucu Arapaima gigas farmed in the Rio Preto da Eva, Amazonas state. Ninety-eight (98) out of 100 examined fish showed to be parasitized. Five hundred and ninety larvae of Hysterothylacium sp. were collected from the intestines, stomach and pyloric caeca. The mean intensity of parasite indexes was 6.02 (+/-5.75) ranging from 1 to 40 larvae per host and the mean abundance was 5.9 (+/-5.76). The A. gigas is the new host record for larvae of Hysterothylacium sp. in Brazil, and this is the first record of larvae of Hysterothylacium (Nematoda: Anisakidae) with zoonotic potential in the pirarucu from South America. PMID- 26675899 TI - Growth of Haematococcus pluvialis Flotow in alternative media. AB - Current study investigates the effect of two alternative media NPK (20-5-20) fertilizer and NPK plus macrophyte (M+NPK) compared to the commercial medium (WC) under growth rate and physiological parameters in batch culture mode (2-L), and verifies whether the use of fertilizer (NPK) and macrophyte (Eichhornia crassipes) would be a good tool for Haematococcus pluvialis culture in the laboratory. The highest number of cells of H. pluvialis has been reported in NPK medium (5.4 * 105 cells.mL-1) on the 28th day, and in the M+NPK and WC media (4.1 * 105 cells.mL-1 and 2.1 * 105 cells.mL-1) on the 26th day, respectively. Chlorophyll-a contents were significantly higher (p<0.05) in NPK medium (41-102 ug.L-1) and lower in WC and M+NPK media (14-61 ug.L-1). The astaxanthin content was less than 0.04 mg.L-1. Production cost of 10-L of H. pluvialis was low in all media, and NPK and M+NPK media had a cost reduction of 65% and 82%, respectively when compared with commercial medium (WC). The use of a medium based on commercial fertilizer and macrophyte (E. crassipes) produced a new medium formulation that proved to be efficient, at least in batch culture mode, in promoting high density culture of H. pluvialis. NPK and macrophyte (E. crassipes) medium seems to be an adequate alternative to replace the conventional one (WC). PMID- 26675900 TI - Seedling survival of Handroanthus impetiginosus (Mart ex DC) Mattos in a semi arid environment through modified germination speed and post-germination desiccation tolerance. AB - Uniform rapid seed germination generally forms a great risk for the plant population if subsequent intermittent precipitation causes desiccation and seedling death. Handroanthus impetiginosus can be found commonly in a wide range of biomes within Brazil including those that are semi-arid. Germination and early growth was studied to understand how germinated seeds survive under these stringent conditions. Accessions were sampled from four seasonally dry biomes in Brazil. Precipitation at the start of the rainy season in the Caatinga, a semi arid biome, is less predictable and the number of successive dry days per dry interval in the first four months of the rainy season was higher than in the other studied biomes. Plants from the Caatinga produced thicker seeds and this trait concurred with slow germination and stronger osmotic inhibition of germination across the accessions, forming a stress avoidance mechanism in the Caatinga. Post-germination desiccation tolerance was high in the Caatinga accession, could be re-induced in accessions from biomes with more regular precipitation (Cerrado and transition zone), but remained poor in the Cerradao accession; thus forming a stress tolerance mechanism. Production of adventitious roots ascertained survival of all tested individuals from all four locations, even if protruded radicles did not survive desiccation, forming an additional stress tolerance mechanism. A sequence of stress avoidance and stress tolerance mechanisms in seeds and germinated seeds was associated with precipitation patterns in different biomes. These mechanisms purportedly allow rapid seedling establishment when conditions are suitable and enable survival of the young seedling when conditions are adverse. PMID- 26675901 TI - Diagnosis of bovine tuberculosis: review of main techniques. AB - Bovine tuberculosis (BTB) remains an important economic and zoonotic problem in Latin America. Traditionally, the fight against BTB is initiated by the implementation of routine diagnostic tests for certification of free properties. The diagnosis of BTB can be made by direct and indirect methods, in which we can mention clinical, post mortem, histopathological, immunological, bacteriological and molecular methods. The renewal of scientific interest in tuberculosis in recent year has led to develop and improve methods of diagnosis, prevention, control and eradication of BTB. The aim of this review is to present and discuss different diagnosis methods of BTB. PMID- 26675902 TI - Genetic differentiation in the populations of red piranha, Pygocentrus nattereri Kner (1860) (Characiformes: Serrasalminae), from the river basins of northeastern Brazil. AB - The red piranha, Pygocentrus nattereri, is an important resource for artisanal and commercial fisheries. The present study determines the genetic differentiation among P. nattereri populations from the northeastern Brazilian state of Maranhao. The DNA was isolated using a standard phenol-chloroform protocol and the Control Region was amplified by PCR. The PCR products were sequenced using the didesoxyterminal method. A sequence of 1039 bps was obtained from the Control Region of 60 specimens, which presented 33 polymorphic sites, 41 haplotypes, ? =0.978 and pi =0.009. The neutrality tests (D and Fs) were significant (P < 0.05) for most of the populations analyzed. The AMOVA indicated that most of the molecular variation (72%) arises between groups. The fixation index was highly significant (FST = 0.707, P < 0.00001). The phylogenetic analyses indicated that the specimens represented a monophyletic group. Genetic distances between populations varied from 0.8% to 1.9%, and were <0.5% within populations. The degree of genetic differentiation found among the stocks of P. nattereri indicates the need for the development of independent management plans for the different river basins in order to preserve the genetic variability of their populations. PMID- 26675903 TI - Evaluation of two Brazilian indigenous plants for phytostabilization and phytoremediation of copper-contaminated soils. AB - Indigenous plants have been grown naturally and vigorously in copper contaminated soils. Thus, the aim of this study was to evaluate the phytoremediation ability of two indigenous plants naturally grown in two vineyard soils copper contaminated, and in a copper mining waste. However, it was evaluated the macro and micronutrient uptake and the potential of phytoremediation. So, a greenhouse study was carried out with Bidens pilosa and Plantago lanceolata in samples of vineyard soils (Inceptisol and Mollisol) copper contaminated, and in a copper mining waste. Plant growth, macro and micronutrient up take, tolerance index (TI), translocation factor (TF), metal extraction ratio (MER), bioaccumulation factor (BCF), plant effective number of the shoots (PENs), and plant effective number of the total plant (PENt) were analyzed. Both plants grown in vineyard soils showed high phytomass production and TI. P. lanceolata plants cultivated in the Inceptisol showed the highest copper concentrations in the shoots (142 mg kg 1), roots (964 mg kg-1) and entire plants (1,106 mg kg-1). High levels of copper were phytoaccumulated from the Inceptisol by B. pilosa and P. lanceolata with 3,500 and 2,200 g ha-1 respectively. Both B. pilosa and P. lanceolata plants showed characteristics of high copper hyperaccumulator. Results showed that both species play an important role in the natural copper phytoaccumulation in both vineyard soils contaminated with copper, being important to its phytoremediation. PMID- 26675904 TI - Population genetics of Chrysoperla externa (Neuroptera: Chrysopidae) and implications for biological control. AB - Green lacewings are insects with great potential to be use in the biological control of agricultural pests, but relatively few studies have attempted to understand the genetic structure of these agents, especially those of predatory insects. The purpose of this study was to characterize genetically populations of C. externa using sequences of subunit I of the cytochrome oxidase, a mitochondrial gene, and examine the population structure of this species in sampled areas in Sao Paulo state. The results indicate high genetic diversity but no genetic structure, detected by AMOVA analysis, and high levels of haplotype sharing in the network. These genetic patterns could be a consequence of environmental homogeneity provided by agroecosystem (citrus orchard), allowing gene flow among populations. Probably there is a unique population in the area sampled that could be used as a population (genetic) source for mass-reared and posterior release in these farms. PMID- 26675905 TI - Ecotoxicological evaluation of sediments applied to environmental forensic investigation. AB - The present study aimed to evaluate the potential for using toxicity assays with sediment samples for the detection of water pollution caused by the discharge of tannery effluents into water bodies and its application to environmental forensic investigation. The study included ecotoxicological evaluation of sediments, survey of benthic organisms in the field, as well as chromium, cadmium and lead dosage which provided data for a sediment quality triad evaluation. The sediment samples showed acute and chronic toxicity to the bioindicators, low biodiversity of benthic macrofauna and high chromium concentration, reaching up to 4365 mg.Kg 1. A close relationship was observed between the separate results of ecotoxicological sediment evaluation and the sediment quality triad. The sediment ecotoxicological assessment proved to be applicable to tracking sources of contamination related to tanneries and similar activities in environmental forensics. PMID- 26675906 TI - Structure of the parasite infracommunity of Sciades proops from the Japaratuba River Estuary, Sergipe, Brazil. AB - The catfish species Sciades proops inhabits muddy estuaries and shallow brackish lagoons, as well as freshwater. For these reasons, it is believed that this species may act as an intermediate, definitive and paratenic host in the life cycle of many parasites. From November 2010 to November 2011 and from August 2012 to July 2013, a total of 126 specimens of Sciades proops from the estuarine region of the Japaratuba River in the state of Sergipe, Brazil, were examined for parasites, of which 84.13% were infected by at least one species: Ergasilus sp. (Copepoda) (Prevalence P = 77.78%, Mean of Intensity MI = 10.08 +/- 15.48, Mean Abundance MA = 14.27 +/- 7.48) in the gills, Contracaecum sp. (P = 23.02%, MI = 20.59 +/- 80.58, MA =39.12 +/- 4.47) in the general cavity, Procamallanus sp. (P = 0.79%, MI = 1, MA = 0.01 +/- 0.09), Raphidascaroides sp. (P = 2.31%, MI = 1.33 +/- 0.58, MA = 0.33 +/- 0.22) and Cuccullanus sp. (Nematoda) (P = 0.79%, MI = 1, MA = 0.01 +/- 0.09) in the intestine, Ancyrocephalinae (Monogenea) (P = 0.79%, MI = 1, MA = 0.01 +/- 0.09) in the gills, Pseudoacanthostomumpanamense (P = 1.59%, MI = 9.00 +/- 8.49, MA = 0.14 +/- 1.36) in the intestine, Clinostomum sp. (P = 1.59%, MI = 17.50 +/- 23.33, MA = 0.29 +/- 3.03) on the body surface and two unidentified metacercariae, referred to as Metacercaria 1 (P = 0.79%; IM = 1, MA = 0.01 +/- 0.09) and Metacercaria 2 (Digenea) (P = 0.79%, MI = 7, MA = 0.06 +/- 0.62) in the swim bladder. Ergasilus sp. was the dominant species and thus classified as core, with Contracaecum sp. as the satellite and other species as secondary species. The spatial distribution of infection with Ergasilus sp. and Contracaecum sp. showed a typical pattern of aggregate distribution. The sex of the host did not influence parasitic infections, but infection with Ergasilus sp. showed a positive and significant correlation with biometric and epidemiologic parameters, whereas infection with Contracaecum sp. was correlated only with prevalence and abundance. PMID- 26675907 TI - Distribution and density of the mollusk Donax striatus (Linnaeus, 1767) in a tropical estuarine region in the brazilian semi-arid. AB - This study evaluated the spatial and temporal distribution and density of the bivalve Donax striatus, at beaches close to the Apodi/Mossoro River estuary, through, six semiannual sampling campaigns were performed between April/2009 and October/2011. The sampled area was delimited by 20 transects that were laid perpendicular to the beach line and extended over 300 m in the intertidal zone. Seven sampling points were established in each transect, organisms and sediment were collected, and water temperature and salinity were recorded. The highest D. striatus average density (103 individuals.m-2) was observed in April/2009 and the lowest (18 individuals.m-2) in October/2010. The highest D. striatus densities occurred in beaches further from the estuarine region as demonstrated by a significant positive correlation (r2 = 0.67 and p = 0.0007). The D. striatus densities presented significant negative correlations with the percentages of organic matter in the water. This species demonstrated an aggregated distribution in the studied area. PMID- 26675908 TI - Antimicrobial and antioxidant activities of Enterococcus species isolated from meat and dairy products. AB - Lactic acid bacteria (LAB) have an important role in a great variety of fermented foods. In addition to their contribution to sensory characteristics, they enhance food preservation and can be used as probiotics. In this study, the antimicrobial and antioxidant activities of culture supernatants and cell free extracts of 16 LAB isolated from meat and dairy products were investigated. The bacterial were identified by 16S rRNA sequencing. GenBank BLAST analysis revealed that all the isolates belong to Enterococcus faecium species. Antimicrobial activity against the indicator microorganism (Listeria monocytogenes) was observed at 11 culture supernatants and 4 cell free extracts. The sensibility of culture supernatant was evaluated by proteinase K and trypsin and it was observed that activity of antimicrobial substance was completely lost after the treatment. All of the isolates showed antioxidant activity as determined by the Thiobarbituric Acid Reactive Substances (TBARS) method with both types of extracts. When the antioxidant capacity was investigated using ABTS*+ method (2,2 azino-bis (3 ethylbenzothiazoline-6-sulfonic acid)) and DPPH method (2,2-diphenyl-1 picrylhydrazyl) it was observed that only culture supernatants showed antioxidant capacity. These bacteria could particularly help to reduce or inhibit pathogenic microorganisms as well as oxidative spoilage in foods and feed. PMID- 26675909 TI - Trace elements concentrations in Buff-breasted Sandpiper sampled in Lagoa do Peixe National Park, Southern Brazil. AB - Cadmium, cobalt, chromium, copper, manganese, nickel, zinc and lead concentrations were detected in feathers of Buff-breasted Sandpipers (Calidris subruficollis) captured during the non-breeding season and analyzed with relationship to body mass. Of these metals tested for, only copper levels (2.28 ug/g) were positively correlated with bird body mass. Zinc levels showed higher concentration (67.97 ug/g) than the other metals, and cadmium levels showed the lowest concentration (0.14 ug/g). Trace element concentrations were below toxicity levels for all tested chemicals and we suggest that this probably reflects that essential elements are maintained there by normal homeostatic mechanism and that no excessive environmental exposure to these elements during migration or on the wintering area is suggested by these results. PMID- 26675910 TI - New records of the striped cleaner shrimp Lysmata grabhami (Gordon, 1935) from Brazil, Southwestern Atlantic. AB - New records for Lysmata grabhami (Gordon, 1935) in Brazilian waters are presented. Four adult individuals from coastal waters off the city of Vitoria, Espirito Santo coast and one adult from Trindade Island were collected during scuba diving in depths between 20-40 meters. These two records represent the southernmost published finding of this species in the Atlantic and the record for Vitoria, Espirito Santo is the first from Brazilian coastal waters. PMID- 26675911 TI - Influence of nitrogen sources on the enzymatic activity and grown by Lentinula edodes in biomass Eucalyptus benthamii. AB - Lignocellulose is the most abundant environmental component and a renewable organic resource in soil. There are some filamentous fungi which developed the ability to break down and use cellulose, hemicellulose and lignin as an energy source. The objective of this research was to analyze the effect of three nitrogen resources (ammonium sulfate, saltpetre, soybean) in the holocellulolitic activity of Lentinula edodes EF 50 using as substrate sawdust E. benthamii. An experimental design mixture was applied with repetition in the central point consisting of seven treatments (T) of equal concentrations of nitrogen in ammonium sulfate, potassium nitrate and soybean. The enzymatic activity of avicelase, carboxymetilcellulase, beta-glucosidase, xylanases and manganese peroxidase was determined. The humidity, pH, water activity (aw) and qualitative analysis of mycelial growth in 8 times of cultivation were evaluated. The results showed negative effect on enzyme production in treatments with maximum concentration of ammonium sulfate and potassium nitrate. The treatments with cooked soybean flour expressed higher enzymatic activities in times of 3, 6 and 9 days of culture, except in the activity of manganese peroxidase. The highest production was observed in the treatment with ammonium sulfate, and soybean (83.86 UI.L-1) at 20 days of cultivation. PMID- 26675913 TI - Hematological, morphological and morphometric characteristics of blood cells from rhea, Rhea Americana (Struthioniformes: Rheidae): a standard for Brazilian birds. AB - Blood exams are an indispensable tool in bird medicine. This study aimed at describing values and aspects of rheas' hematology, Rhea americana, as well as analyzing the morphology and morphometry of all blood cells. Fifty eight adult rheas of both sexes from two farms, one in Cachoeiro de Itapemirim, Espirito Santo State and the other in Sao Carlos, Sao Paulo State, were selected. Blood samples were taken and RBC count, PCV and Hb levels measured and used in hematimetric indexes calculations. The total and differentiated leukocyte counts, as well as the TPP and fibrinogen were determined. Erythrocytes, leukocytes and thrombocytes were identified and characterized morphologically. The values for the red series and hematimetric indexes were: RBC (2.81 +/- 0.15 * 106/MUL), PCV (44.20 +/- 2.86%), Hb (12.12 +/- 0.74 g/dL), MCV (15.75 +/- 0.89 fL), MCH (43.18 +/- 1.82 pg), MCHC (27.44 +/- 0.80 g/dL); the values of white series were: WBC (12.072 +/- 4116/MUL), heterophils (64.10 +/- 9.90%), eosinophils (2.05 +/- 2.06%), monocytes (6.40 +/- 2.99%), lymphocytes (26.93 +/- 9.62%), basophils (0.52 +/- 1.27%). One may conclude that on average, rheas' blood cells are larger than those of other birds, but these cells in smears cannot be differentiated only by their size. Besides rheas' leukocytes have different components and coloring as in other bird species, however, there are no components or staining aspects unique to the species. PMID- 26675912 TI - Antioxidant activity and phenolic content of leaf infusions of Myrtaceae species from Cerrado (Brazilian Savanna). AB - There is considerable interest in identifying new antioxidants from plant materials. Several studies have emphasized the antioxidant activity of species belonging to the Myrtaceae family. However, there are few reports on these species from the Cerrado (Brazilian savanna). In this study, the antioxidant activity and phenolic content of 12 native Myrtaceae species from the Cerrado were evaluated (Blepharocalyx salicifolius, Eugenia bimarginata, Eugenia dysenterica, Eugenia klotzschiana, Hexachlamys edulis, Myrcia bella, Myrcia lingua, Myrcia splendens, Myrcia tomentosa, Psidium australe, Psidium cinereum, and Psidium laruotteanum). Antioxidant potential was assessed using the antioxidant activity index (AAI) by the DPPH method and total phenolic content (TPC) by the Folin-Ciocalteu assay. There was a high correlation between TPC and AAI values. Psidium laruotteanum showed the highest TPC (576.56 mg GAE/g extract) and was the most potent antioxidant (AAI = 7.97, IC50 = 3.86 ug.mL-1), with activity close to that of pure quercetin (IC50 = 2.99 ug.mL-1). The extracts of nine species showed IC50 of 6.24-8.75 ug.mL-1. Most species showed TPC and AAI values similar to or higher than those for Camellia sinensis, a commonly consumed tea with strong antioxidant properties. The results reveal that the analyzed Myrtaceae species from the Cerrado possess high phenolic contents and antioxidant activities. Thus, they are a potential source of new natural antioxidants. PMID- 26675914 TI - Helminth parasite communities of two Physalaemus cuvieri Fitzinger, 1826 (Anura: Leiuperidae) populations under different conditions of habitat integrity in the Atlantic Rain Forest of Brazil. AB - Adults of Physalaemus cuvieri were collected and necropsied between November 2009 and January 2010. This was carried out in order to report and compare the helminth fauna associated with two populations of this anuran species from the Brazilian Atlantic rain forest under different conditions of habitat integrity. The hosts from the disturbed area were parasitized with five helminth taxa: Cosmocerca parva, Aplectana sp., Physaloptera sp., Rhabdias sp., Oswaldocruzia subauricularis (Nematoda) and Polystoma cuvieri (Monogenea) while those from the preserved area had four helminth taxa: C. parva, Aplectana sp., Physaloptera sp., Rhabdias sp., and Acanthocephalus saopaulensis (Acanthocephala). Prevalence, mean intensity of infection, mean abundance, mean richness, importance index and dominance frequency of helminth component communities were similar in both areas. The helminth community associated with anurans from the disturbed area had higher diversity than that from the preserved area. This study is the first to report on the acanthocephalan parasites of Ph. cuvieri, and the similarity between helminth fauna composition of two host populations under different selective pressures. PMID- 26675915 TI - Biology and fertility life table of Eriopis connexa, Harmonia axyridis and Olla v nigrum (Coleoptera: Coccinellidae). AB - The coccinellids Eriopis connexa (Germar), Harmonia axyridis (Pallas) and Olla v nigrum (Mulsant) are important natural biological control agents. The purpose of this paper was to study the biology and create a fertility life table of these three coccinellid species. For the biology study, 50 insects/species were used and kept in groups of 10 in glass vials (2300 cm3). For the three species studied, the viability of the total cycle varied from 45 to 50%. O. v-nigrum was the species which presented the longest oviposition period. However, H. axiridis demonstrated the best reproductive performance and ability of population growth in each generation. In conclusion, the use of commercially obtained pollen and A. kuenhiella eggs enables the development of coccinellids E. connexa, H. axyridis and O. v-nigrum under laboratory conditions, since the insects completed their biological cycle and originated adults with good reproductive performance. PMID- 26675916 TI - Effects of ethanol consumption and alcohol detoxification on the biomechanics and morphology the bone in rat femurs. AB - The objective of this study was to verify the effects of ethanol consumption and alcohol detoxification on the biomechanics, area and thickness of cortical and trabecular bone in rat femur. This was an experimental study in which 18 male Wistar rats were used, with 40 days of age, weighing 179 +/- 2.5 g. The rats were divided into three groups (n=06): CT (control), AC (chronic alcoholic), DT (detoxification). After experimental procedures, the animals were euthanized by an overdose of the anesthetic and their femurs were collected for mechanical testing and histological processing. All animals did not present malnutrition or dehydration during experimentation period. Morphometric analysis of cortical and trabecular bones in rat femurs demonstrated that AC animals showed inferior dimensions and alcohol detoxification (DT) allowed an enhancement in area and thickness of cortical and trabecular bone. Material and structural properties data of AC group highlighted the harmful effects of ethanol on bone mechanical properties. The results of this study demonstrated that chronic alcoholic rats (AC) presented major bone damage in all analyzed variables. Those findings suggested that alcohol detoxification is highly suggested in pre-operative planning and this corroborates to the success of bone surgery and bone tissue repair. Thanks to the financial support offered by PROBIC - UNIFENAS. PMID- 26675917 TI - Redescription of Campoletis sonorensis (Cameron, 1886) (Hymenoptera, Ichneumonidae, Campopleginae), parasitoid of Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera, Noctuidae) in Brazil. AB - The fall armyworm Spodoptera frugiperda (Lepidoptera; Noctuidae) is a voracious pest of numerous crops of economic importance throughout the New World. In Brazil, its larvae are attacked by several species of parasitoid wasps, making them potential candidate as biological control agents against this pest. A survey of the parasitoid fauna on S. frugiperda in maize crops throughout Brazil reveals two species of Campoletis, which are morphologicaly very similar species. In this paper we combine these data with pictures from the type material of C. sonorensis and C. flavicincta, as well as their descriptions to provide a redescription to Campoletis sonorensis (Cameron, 1886) using for this both morphological characters and DNA Barcoding (Hebert et al., 2003) information, in an attempt to help with the correct identification of the taxa to improve biological control studies. PMID- 26675918 TI - Edge effects on the blowfly fauna (Diptera, Calliphoridae) of the Tijuca National Park, Rio de Janeiro, Brazil. AB - In this contribution we examine the diversity, abundance and species richness of Calliphoridae in the Tijuca National Park, Rio de Janeiro, RJ. Specimens were collected monthly between September 2009 and August 2010, using sardines as bait, in three points: A, on the forest edge (22 degrees 56'846"S 43 degrees 17'496"W), B, 700 m from it (22 degrees 57'073"S 43 degrees 17'832"W) and C, 1,200 m into the forest (22 degrees 57'321"S 43 degrees 18'031"W), evaluating the indicator species at each point and the anthropogenic influences and abiotic factors that determine species distribution. A total of 16,364 Calliphoridae were collected and 17 species were identified. Species abundance was strongly positively correlated with temperature. The greatest number of flies was collected at A, but in this point, diversity was lower and most individuals collected belonged to the dominant species. Point C, conversely, had the lower abundance and the highest diversity. Chrysomya megacephala, an urban and synanthropic species, was dominant at point A, whereas Laneela nigripes and Mesembrinella peregrina, typically forest species, were considered indicators at points B and C, respectively, showing that the anthropogenic influence is more intense at the forest edge. PMID- 26675919 TI - The impact of anthropogenic food supply on fruit consumption by dusky-legged guan (Penelope obscura Temminck, 1815): potential effects on seed dispersal in an Atlantic forest area. AB - Frugivorous birds are important seed dispersers and influence the recruitment of many plant species in the rainforest. The efficiency of this dispersal generally depends on environment quality, bird species, richness and diversity of resources, and low levels of anthropogenic disturbance. In this study, we compared the sighting number of dusky-legged guans (Penelope obscura) by km and their movement in two areas of Serra do Japi, one around the administrative base (Base) where birds received anthropogenic food and a pristine area (DAE) with no anthropogenic resource. We also compared the richness of native seeds in feces of birds living in these two areas. Although the abundance of P. obscura was higher in the Base, these individuals moved less, dispersed 80% fewer species of plants and consumed 30% fewer seeds than individuals from DAE. The rarefaction indicated a low richness in the frugivorous diet of birds from the Base when compared to the populations from DAE. We conclude that human food supply can interfere in the behavior of these birds and in the richness of native seeds dispersed. PMID- 26675920 TI - Impact assessment of the introduction of Cichla kelberi in a large Neotropical reservoir and its lateral lagoons (Upper Parana River Basin, Brazil). AB - This study aimed to understand how the introduction of Cichla kelberi in Rosana Reservoir (Paranapanema River) affected the native ichthyofauna. Data on the structure of the small fish fauna assemblage were obtained before and after the introduction of this carnivorous species. Samplings were carried out in February and September of 2004, previously to the register of Cichla kelberi in the reservoir, and after its introduction, November of 2004, January, March, May and August of 2005, February and June of 2006, February and July of 2007, February and October of 2008 and February of 2009. A total of 4,693 fish, belonging to 43 different species was sampled between 2004 and 2009. The order Characiformes was the most abundant, followed by Perciformes and Siluriformes. Comparative analyses, before and after the introduction, could not demonstrate significant changes in composition, richness, abundance, biomass, mean length and diversity of fish. Aquatic insects were the main feeding item of C. kelberi, followed by tetragonopterinae fish. Cannibalism was recorded during the whole study period. The results showed that Cichla cannot deeply affect the ichthyofauna assemblages of a large Neotropical reservoir, at least in a short or medium term period after its introduction. The results also allowed concluding that the introduction of C. kelberi in the reservoir is in the phase 3. In this phase, the specie can survive and reproduce in the new environment; however it is not totally established and disseminated. The reasons for the fact that Cichla is still not dominant in Rosana Reservoir could be related to feeding competition, high rate of cannibalism and the presence of large amount of aquatic macrophytes (refuge zones). In spite of the results, the continuous monitoring of the role of non native species on the local fish fauna is absolutely necessary because the impacts caused by colonization of this undesirable species can be magnified by complex processes, usually correlated with other environmental disturb, especially the negative effects of damming. PMID- 26675921 TI - Feather mites of Calidris fuscicollis (Aves: Scolopacidae) in Brazil. AB - During the period 2010-2012, eighty individuals of Calidris fuscicollis (Vieillot, 1819) were collected on the southern coast of Rio Grande do Sul, Brazil, with the objective of determining the presence of feather mites. Of the 80 birds examined, 32.5% were infested by mites, identified as Avenzoaria calidridis (Oudemans, 1904) (Avenzoariidae) (31.25%), Montchadskiana securicata (Megnin & Trouessart 1884) (Pterolichidae) (22.5%) and Alloptes limosae (Dubinin, 1951) (Alloptidae) (6.25%). This is the first report of feather mites on Calidris fuscicollis in Brazil. PMID- 26675922 TI - Perkinsus sp. infecting the oyster Crassostrea rhizophorae from estuaries of the septentrional Northeast, Brazil. AB - The mangrove oyster Crassostrea rhizophorae is an estuarine resource exploited by riverside communities in Northeast Brazil. Despite its socioeconomic importance, studies on the health status of this bivalve are scanty in this region. The purpose of the present study was to investigate the presence of the protozoan Perkinsus sp. in C. rhizophorae collected in August and September 2011 in three estuaries of the septentrional Northeast, Brazil: Jaguaribe (Ceara), Camurupim (Piaui) and Carnaubeiras (Maranhao) (n= 150 specimens/site). The samples were submitted to Ray's fluid thioglycollate medium (RFTM), PCR and histology assays. The RFTM assay revealed spherical, blue or bluish-black hypnospores of the genus Perkinsus in 50 specimens (Jaguaribe= 17.3%, Camurupim= 5.3%, Carnaubeiras= 10.6%). The intensity of the infection ranged from very light (1-10 cells per slide) to severe (more than 40 cells in each of 10 fields of the slide) for Jaguaribe; very light for Camurupim and very light to moderate (at least 40 cells observed in each of 10 fields of the slide) for Carnaubeiras. When submitted to confirmatory PCR analysis, 6 cases were confirmed (Jaguaribe=3, Camurupim=1, Carnaubeiras=2). The histology confirmed 21 cases of infection in specimens from the three estuaries. Although local collectors have reported no mortality in oyster populations that might be attributed to infection by Perkinsus, health surveillance of oyster populations in the septentrional region of Northeast Brazil is advisable. PMID- 26675923 TI - Translocation of Harpy Eagle (Harpia harpyja) (Linnaeus, 1758) nest. PMID- 26675924 TI - Association between leukocyte count and sarcopenia in postmenopausal women: The Korean National Health and Nutrition Examination Survey. AB - OBJECTIVE: To investigate the association between leukocyte counts and sarcopenia according in postmenopausal women. STUDY DESIGN: Cross-sectional study. MAIN OUTCOME AND MEASURES: We examined the relationship between leukocyte counts and sarcopenia in 2152 post-menopausal Korean women who participated in the 2010-2011 Korean National Health Examination and Nutrition Survey. Sarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by weight (%) that was greater than 1SD below the mean of young adults. The odds ratios (ORs) for sarcopenia were calculated using multiple logistic regression across leukocyte count quartiles (Q1:<=4710, Q2:4720-5600, Q3:5610-6600, and Q4:>=6610cells/MUL) after adjusting for confounding variables. RESULTS: The prevalence of sarcopenia gradually increased in accordance with leukocyte quartiles. Compared with the lowest quartile of leukocyte counts, the corresponding OR (95% CI) of the highest quartile of leukocyte counts for sarcopenia was 2.41 (1.12-5.22) after adjusting for age, waist circumference, cigarette smoking, alcohol intake, regular exercise, blood pressure, fasting plasma glucose, triglyceride, and HDL cholesterol. CONCLUSIONS: Leukocyte counts were positively related to a higher risk of sarcopenia in postmenopausal women. PMID- 26675925 TI - A Call to Action: Intensify the Investigation of Relatively Rare Tumors of the Gastrointestinal Tract. PMID- 26675926 TI - Effect of Transfusion Strategy in Acute Non-variceal Upper Gastrointestinal Bleeding: A Nationwide Study of 5861 Hospital Admissions in Denmark. AB - BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of admissions as well as aggressive transfusion of blood products. Whether the transfusion strategy in NVUGIB impacts on hemostasis is unknown and constitutes the focus of this study. METHOD: Retrospective analysis of all hospital admissions in Denmark between 2011 and 2013 where hemostatic endoscopic interventions in either the stomach or duodenum had been employed. Regression modeling was used to predict the effect of units transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets (PLT) on primary outcome 30-day mortality as well as secondary hemostasis-related outcomes and need for re endoscopy and conversion to surgery. The model was corrected for confounders, including transfusion of other blood products (PRBC, FFP, and PLT, respectively), patient age as well as pre-existing medical conditions. RESULTS: 5107 patients received 10783 therapeutic endoscopic interventions. Units of PRBC transfused were identified as a predictor of re-endoscopy, surgery, and 30-day mortality with odds ratio (OR) 1.08 (1.06-1.09, p < 0.01), 1.05 (1.03-1.07, p < 0.01), and 1.04 (1.01-1.06, p < 0.01), respectively. Units of FFP transfused were associated with a higher risk of surgery and 30-day mortality with OR 1.05 (1.02-1.08, p < 0.01) and 1.04 (1.02-1.07, p < 0.01), respectively. Units of PLTs transfused were independently associated with a reduction in risk of re-endoscopy 0.93 (0.87 0.98, p = 0.02). A high ratio of PRBC:FFP:PLT (1:1:1) was associated with reduced need for re-endoscopy OR 0.23 (0.06-0.67, p = 0.01) but increased mortality with OR 3.60 (1.34-11.38, p = 0.02). CONCLUSION: PRBC transfusion was associated with adverse events, including 30-day mortality and failure of hemostasis. In contrast, transfusion of PLT was associated with a reduction in need for re endoscopy. PMID- 26675927 TI - Patterns of Use and Short-Term Outcomes of Minimally Invasive Surgery for Malignant Pheochromocytoma: A Population-Level Study. PMID- 26675928 TI - Surgical Management of Chronic Wounds in a Buruli Ulcer Endemic Area in Central Africa. AB - BACKGROUND: Chronic wounds, especially Buruli ulcers (BU) are emerging public health threat in West and Central Africa. Akonolinga in Cameroon is one of the four health districts affected by BU. Since 2002, Medecins Sans Frontieres has established a specialized wound carecenter to actively diagnose and provide treatment of chronic wounds that is accessible and affordable for all patients. Our objectives were to report the surgical activities in Akonolinga, to provide description of the types of chronic wounds and elements of anticipation of treatment needs in a public health perspective. METHOD: We carried out a retrospective cohort and descriptive study from January 2012 to June 2014 (30 months) on a series of consecutive patients with chronic wounds, managed surgically in Akonolinga, Centre Region, Cameroon. Among BU patients only those with necessity of surgery were included and the others followed only their 8 weeks medical treatment with antibiotics. RESULTS: A total of 148 patients were recorded. 101 cases of BU and related disability and 47 cases of non-Buruli chronic wounds. Patients had a mean age of 34 years. Most of the procedures used were debridement 40 %, skin graft 29 %, stripping 5 %, plastic procedures 7 %, and amputation 4 %. The mean number of procedures was 2 for each patient in this series. CONCLUSION: Chronic wounds occur worldwide and may be caused by specific health conditions. Medical and paramedical education should provide both the theoretical knowledge and practical skills to help health care personnel to face this problem in their communities. PMID- 26675929 TI - Cost Per DALY Averted in a Surgical Unit of a Private Hospital in India. AB - BACKGROUNDS: Cost-effectiveness analysis plays an important role to guide resource allocation decisions, however, information on cost per disability adjusted life year (DALY) averted by health facilities is not available in many developing economies, including India. We estimated cost per DALY averted for 2611 patients admitted for surgical interventions in a 106-bed private for-profit hospital in northern India. METHODS: Costs were calculated using standard costing methods for the financial year 2012-2013, and effectiveness was measured in DALYs averted using risk of death/disability, effectiveness of treatment and disability weights from 2010 global burden of disease study. RESULTS: During the study period, total operating cost of the hospital for treating surgical patients was USD 1,554,406 and the hospital averted 9401 DALYs resulting in a cost per DALY averted of USD 165. CONCLUSIONS: Even though this study was based on one hospital in India, however, the hospital is a private hospital which is expected to have less surgical case load compared to government health facilities, cost per DALY averted for the surgical interventions is much lower than the cost-effectiveness threshold for India (USD 1508 in 2012). This study therefore provides evidence to re-think the common notion that surgical care is expensive and therefore of lower value than other health interventions. PMID- 26675930 TI - EBSLN and Factors Influencing its Identification and its Safety in Patients Undergoing Total Thyroidectomy: A Study of 456 Cases. AB - BACKGROUND: The external branch of the superior laryngeal nerve (EBSLN) is at surgical risk during superior thyroid pole ligation during thyroidectomy. Majority of studies have addressed the identification of these nerves and its reported incidence. Very few studies have addressed the relationship of these nerves with the volume of the thyroid gland and presence of toxicity. MATERIALS AND METHODS: A retrospective evaluation of 456 patients who underwent total thyroidectomy were analysed from the prospectively maintained database. The EBSLN was diligently identified and preserved before individual ligation of the superior thyroid pedicle. The nerve was graded as per the Cernea classification (type I, IIa and IIb). Goitres are classified into toxic & non-toxic based on hyperthyroidism, further sub classified as large (>50 cc) and small (<=50 cc) based on volume of each lobe. The grading of EBSLN was correlated with hyperthyroidism and volume of each lobe. RESULTS: In 456 patients (912 nerves), EBSLN was identified in 849/912(93.09%), type I in 156/912(17.1%), type IIa in 522/912(57.23%) and type IIb in 171/912(18.75%). The prevalence of large goitres was 180/912(19.73%).Type IIb nerve was predominantly seen in 161/180(89.4%) of large goitres. Type IIb nerves was more common in toxic 141/372(37.9%) than non toxic lobes 25/540(5.46%). CONCLUSION: Large goitres are not uncommon in toxic cases. The EBSLN is at highest risk of injury in this subgroup of patients and surgical expertise is essential to identify this entity of EBSLN to perform a safe thyroidectomy. PMID- 26675931 TI - On the pitfalls of peer review. AB - The review process of academic, scientific research and its basic tenets is considered, thereby distinguishing between (i) reviewing of manuscripts to be published in the scientific literature, (ii) reviewing of research proposals to be financed by funding agencies, (iii) reviewing of educational or research institutions with respect to their proper functioning, and (iv) reviewing of scientists with the aim of appointing or tenuring faculty. PMID- 26675932 TI - Totally laparoscopic complete bursectomy and D2 lymphadenectomy in radical total gastrectomy: an outside bursa omentalis approach. AB - BACKGROUND: Bursectomy is regarded as a standard surgical procedure during gastrectomy for serosa-positive gastric cancer in Japanese gastric cancer treatment guidelines (Japanese Gastric Cancer Association in Gastric Cancer 14:113-123, 2011). As a consequence, bursectomy is widely performed in open gastrectomy. However, laparoscopic gastrectomy with bursectomy is rare. Based on our previous experience of laparoscopic bursectomy in distal gastrectomy (Zou et al. in Oncol Lett 10:99-102, 2015), herein, we described the technique of totally laparoscopic radical total gastrectomy with complete bursectomy using an outside bursa omentalis approach. METHODS: Firstly, the transverse mesocolon and distal gastric membrane were separated from right to left, and the right gastroepiploica vessels were ligated at root with No. 6 lymph nodes (LNs) dissection followed by the pancreas membrane dissection from pancreas head to pancreas tail. Secondly, the anterior plane of transverse mesocolon was dissected from left to right starting from the lower pole of spleen, and the membrane of pancreas tail was separated to combine the pancreas anterior plane with No. 4s, 10, 11d and 2 LNs dissection. Thirdly, the lesser omental was dissected from right to left with No. 5 and 12a LNs dissection, and the duodenum was transected. Then, the No. 7, 8, 9 and 11p LNs were dissected followed by No. 1 LNs dissection. Finally, a Roux-en-Y esophagojejunostomy was carried out intracorporeally with a linear cutter. RESULTS: Thirty-two patients with advanced proximal gastric cancer underwent laparoscopic total gastrectomy with complete bursectomy using an approach outside bursa omentalis. One bowel obstruction and one pulmonary infection were recorded and cured with conservative measure. The mean operative time was 253.3 +/- 31.3 min with a mean blood loss of 90.5 +/- 23.1 ml. The mean length of stay was 10.6 +/- 2.6 days. CONCLUSION: Laparoscopic radical total gastrectomy with complete bursectomy using an outside bursa omentalis approach is feasible and safe in experienced hands with favorable short outcome. Further studies were needed for its advanced application. PMID- 26675933 TI - A comparison of robotic single-incision and traditional single-incision laparoscopic cholecystectomy. AB - BACKGROUND: Surgeons continually strive to improve technology and patient care. One remarkable demonstration of this is the development of laparoscopic surgery. Once this proved to be a safe and reliable surgical approach, robotics seemed a logical progression of surgical technology. The aim of this project was to evaluate the utility of robotics in the context of single-incision laparoscopic cholecystectomy (SILC). METHODS: A retrospective review of a prospectively maintained database of robotic single-incision laparoscopic cholecystectomy (RSILC) and traditional SILC performed by a single surgeon at our institution from July 2010 to August 2013 was queried. All consecutive patients undergoing RSILC and SILC during this time period were included. Primary outcomes include conversion rate and operative time. Secondary outcomes include length of stay, duration of narcotic use, time to independent performance of daily activities and cost. Categorical variables were evaluated using Chi-square analysis and continuous variables using t test or Wilcoxon's rank test. RESULTS: Thirty-eight patients underwent RSILC and 44 underwent SILC. BMI was higher in the RSILC group, and the number of patients with prior abdominal surgeries was higher in the SILC group. Otherwise, demographics were similar between the two groups. There was no difference in conversion rate between RSILC and SILC (8 vs 11 %, p = 0.60). Mean operative time for RSILC was significantly greater compared with SILC (98 vs 68 min, p < 0.0001). RSILC was associated with a longer duration of narcotic use (2.3 vs 1.7 days, p = 0.0019) and time to independent performance of daily activities (4 vs 2.3 days, p < 0.0001). Total cost is greater in RSILC ($8961 vs $5379, p < 0.0001). CONCLUSION: While RSILC can be safely performed, it is associated with longer operative times and greater cost. PMID- 26675934 TI - Endoscopic versus percutaneous drainage of symptomatic pancreatic fluid collections: a 14-year experience from a tertiary hepatobiliary centre. AB - INTRODUCTION: Endoscopic transmural drainage (ED) or percutaneous drainage (PD) has mostly replaced surgery for the initial management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare outcomes for patients undergoing ED or PD of symptomatic PFCs. METHODS: Between January 2000 and December 2013, all patients who required PD or ED of a PFC were included. Rates of treatment success, length of hospital stay, adverse events, re interventions and length of follow-up were recorded retrospectively in all cases. RESULTS: In total, 164 patients were included in the study; 109 patients underwent ED; and 55 had PD alone. During the 14-year study period, the incidence of ED increased and PD fell. In the 109 patients who were managed by ED, treatment success was considerably higher than in those managed by PD (70 vs. 31 %). Rates of procedural adverse events were higher in the ED cohort compared to the PD group (10 vs. 1 %), but patients managed by ED required fewer interventions (median of 1.8 vs. 3.3) had lower rates of residual collections (21 vs. 67 %) and need for surgical intervention (4 vs. 11 %). In the ED group, treatment success was similar for walled-off pancreatic necrosis (WOPN) and pseudocysts (67 vs. 72 %, P = 0.77). There were no procedure-related deaths. CONCLUSION: Compared with PD, ED of symptomatic PFCs was associated with higher rates of treatment success, lower rates of re-intervention, including surgery and shorter lengths of hospital stay. Outcomes in WOPN were comparable to those in patients with pseudocysts. PMID- 26675935 TI - Learning curve for laparoscopic sleeve gastrectomy: role of training in a high volume bariatric center. AB - BACKGROUND: Since the great diffusion of laparoscopic treatment of obesity, there is a growing interest concerning the learning process for those surgeons who undertake the bariatric activity. However, papers analyzing the learning curve (LC) for sleeve gastrectomy (SG) are still scarce. This study aims to investigate whether the LC for SG of a novice bariatric surgeon might be positively influenced by the training in a high-volume bariatric center (HVBC). METHODS: Between October 2010 and January 2014, 128 patients underwent SG by the same young surgeon who previously attended a 2-year training in a HVBC. His LC has been divided into three consecutive periods: in the first period (1st-47th SGs) he operated in the HVBC, while in the second (48th-88th SGs) and third period (89th-128th SGs) he moved to a novel department where surgical and ancillary staff were initially not confident with bariatric procedures but progressively owned the proper experience. Preoperative characteristics, operative data, complications and postoperative results of the three periods were compared. RESULTS: Mean follow-up was 1 year. Preoperative patients' characteristics were homogeneous. No significant differences have been registered among the three periods concerning operative data, mortality, intra- and post-operative complications, weight loss outcomes and comorbidities' resolution. Post-operative follow-up rates at 6 and 12 months were 98.4 and 92.1 %, respectively. CONCLUSIONS: Long-lasting fellowship in a HVBC might allow the novel bariatric surgeon to safely and proficiently overcome the LC for SG, even in a new established bariatric setting. PMID- 26675936 TI - An innovative technique of robotic-assisted/laparoscopic re-pyeloplasty in horseshoe kidney in patients with failed previous pyeloplasty for ureteropelvic junction obstruction. AB - OBJECTIVES: To describe an innovative laparoscopic/robotic-assisted re pyeloplasty technique in patients with recurrent ureteropelvic junction obstruction (UPJO) in horseshoe kidneys. PATIENTS AND METHODS: Data from five patients (37-65, median 54 years) with symptomatic recurrence of UPJO in horseshoe kidney who underwent laparoscopic/robotic-assisted re-pyeloplasty at our institution since 2004 were evaluated retrospectively. The upper ureter together with wedge resection of the pelvis at the lower calyx was performed. The ureter is spatulated till beyond the isthmus and anastomosed to lower calyx. Rotational renal pelvis flap is used for reconstruction and conisation of the pelvis. RESULTS: Median operative time was 137 min (92-180) with a negligible blood loss. There was no need for conversion or revisions. Perioperative periods were uneventful. The intraoperatively inserted JJ was left for 6-8 weeks. Median postoperative differential function of affected kidney at 3 months (MAG III) was 38 % (26-42 %), unchanged from 35 % (21-41 %), preoperatively. This was stable in three patients and higher in two (5 and 7 %). There were no obstructive elements indicating anatomical ureteric obstruction. After convalescence period, three patients recurred to their work at 5 weeks, while all at 8 weeks. All patients remained asymptomatic and have not required any further interventions during whole follow-up. CONCLUSIONS: Described technique of laparoscopic/robotic assisted re-pyeloplasty in horseshoe kidneys is technically feasible, safe and effective with high patient satisfaction and early convalescence. Its success rate is comparable with the results after primary pyeloplasty in horseshoe and heterotopic kidneys. Larger series may be required to allow for more accurate comparison. PMID- 26675937 TI - Endoscopic submucosal resection with a ligation device for the treatment of duodenal neuroendocrine tumors. AB - BACKGROUND: Endoscopic submucosal resection with a ligation device (ESMR-L) is effective for rectal neuroendocrine tumors (NETs); however, its effectiveness for duodenal NETs is unclear. This study evaluated the efficacy and safety of ESMR-L for duodenal NETs. METHODS: A total of 32 consecutive patients with duodenal NETs were treated in our hospital between December 2010 and August 2015. Among these 32 patients, we retrospectively analyzed the data of all patients who underwent ESMR-L for the treatment of duodenal NETs. ESMR-L was considered for patients in whom (1) the lesion size was <=10 mm in diameter, (2) the lesion was located within the submucosal layer, and (3) no lymph node metastasis or distant metastasis was detected. RESULTS: Five patients underwent ESMR-L for the treatment of duodenal NETs. The en bloc complete resection rate was 100 %. The median procedure time for ESMR-L was 15 min (range 10-30 min). In all patients, perforation during and after the operation, and intraoperative bleeding were not observed; however, one patient experienced postoperative bleeding. During follow up, no local recurrence or distant metastasis was noted in any of the patients. CONCLUSION: ESMR-L is feasible, effective, and safe for duodenal NETs measuring <=10 mm in diameter that are confined to the submucosal layer without metastasis. PMID- 26675938 TI - Safety, efficiency and learning curves in robotic surgery: a human factors analysis. AB - BACKGROUND: Expense, efficiency of use, learning curves, workflow integration and an increased prevalence of serious incidents can all be barriers to adoption. We explored an observational approach and initial diagnostics to enhance total system performance in robotic surgery. METHODS: Eighty-nine robotic surgical cases were observed in multiple operating rooms using two different surgical robots (the S and Si), across several specialties (Urology, Gynecology, and Cardiac Surgery). The main measures were operative duration and rate of flow disruptions-described as 'deviations from the natural progression of an operation thereby potentially compromising safety or efficiency.' Contextual parameters collected were surgeon experience level and training, type of surgery, the model of robot and patient factors. Observations were conducted across four operative phases (operating room pre-incision; robot docking; main surgical intervention; post-console). RESULTS: A mean of 9.62 flow disruptions per hour (95 % CI 8.78 10.46) were predominantly caused by coordination, communication, equipment and training problems. Operative duration and flow disruption rate varied with surgeon experience (p = 0.039; p < 0.001, respectively), training cases (p = 0.012; p = 0.007) and surgical type (both p < 0.001). Flow disruption rates in some phases were also sensitive to the robot model and patient characteristics. CONCLUSIONS: Flow disruption rate is sensitive to system context and generates improvement diagnostics. Complex surgical robotic equipment increases opportunities for technological failures, increases communication requirements for the whole team, and can reduce the ability to maintain vision in the operative field. These data suggest specific opportunities to reduce the training costs and the learning curve. PMID- 26675939 TI - Endoscopic revision of gastric bypass: Holy Grail or Epic fail? AB - BACKGROUND: Approximately 20-30 % of patients who undergo Roux-en-Y gastric bypass (RYGB) will not meet the goals of weight loss surgery. Revisional surgery is associated with higher morbidity compared to initial operative management, and results in terms of weight loss have been inconsistent. Endoscopic plication has been seen as a less invasive option, with encouraging initial results. The objective was to analyze the outcomes after Restorative Obesity Surgery, Endolumenal (ROSE) procedure. METHODS: We retrospectively analyzed patients who underwent ROSE between 5/2008 and 11/2013. All patients had failure of weight loss or regain weight after RYGB. Demographics, operative data, and follow-up were recorded. RESULTS: Twenty-seven patients underwent ROSE. One patient was excluded due to lack of follow-up. Twenty-five (96 %) patients were female. Mean time since initial RYGB was 11.9 +/- 4.3 years. Mean initial weight and BMI were 236 +/- 47 lb and 40.6 +/- 8.1 kg/m(2), respectively. Mean OR time was 77 +/- 30 min. Preoperative average pouch length and stoma diameter were 6.8 +/- 2.3 and 2.1 +/- 0.7 cm, respectively. On average, 4 +/- 1.6 stitches were placed. Final pouch length and stoma diameter were 3.4 +/- 1.6 (50 % reduction) and 0.86 +/- 0.4 cm (61 % reduction). A total of 12 (46 %) and seven (28 %) patients underwent EGD at 3 and 12 months postoperatively. The mean pouch length and stoma diameter were 5 +/- 1.9 (26.5 % reduction) and 1.2 +/- 0.7 cm (42.9 % reduction) at 3 months and 6.14 +/- 1.6 (10 % reduction) and 2.2 +/- 1.2 cm (4.7 % increase) at 12 months, respectively. The %EWL was 8.9, 9.3, 8, 6.7, -10.7, -13.5, -5.8, -4.5 at 3, 6, 12, 24, 36, 48, 60, and 72 months, respectively. CONCLUSION: Although endoscopic plication achieved the intended reduction in the pouch and stoma diameter at 3 months, these tend toward the preoperative diameter at 12 months. This anatomical failure and the lack of follow-up may explain why most patients failed to achieve sustainable weight loss. PMID- 26675940 TI - Is expedited early discharge following elective surgery for colorectal cancer safe? An analysis of short-term outcomes. AB - BACKGROUND: Enhanced recovery pathways have become standard practice after elective colorectal surgery to improve postoperative care while reducing length of stay in hospital. However, there is concern that early discharge may result in increased rates of adverse events including readmission. This study aims to determine whether it is safe to discharge patients on postoperative day 1 or 2 if they have undergone an elective colorectal operation for cancer. METHODS: The 2012 American College of Surgeons National Surgical Quality Improvement Program dataset was used. The study included patients who underwent elective colorectal cancer surgery and were discharged on postoperative day (POD) 1 or 2 (expedited early discharge) versus POD 3 or 4 (standard early discharge). Patients who had metastases, concurrent procedures including ostomy creation, or died during admission were excluded. Primary outcomes were 30-day adverse events (serious complications, mortality and reoperations) and readmission rates, which were analyzed using multivariable regression. RESULTS: A total of 305 and 2277 patients were identified in the expedited and standard early discharge groups, respectively. There were 6 (1.97 %) adverse events and 16 (5.56 %) readmissions in the expedited group, compared to 59 (2.59 %) and 135 (6.24 %) in the standard group. No statistical difference was found between the cohorts with respect to 30 day adverse events (OR 0.93, p = 0.87, 95 % CI [0.41-2.12]) or readmission rate (OR 1.03, p = 0.90, 95 % CI [0.61-1.76]). CONCLUSION: Patients discharged by POD 2 after elective oncologic colon resections did not have significantly more adverse events or readmissions compared to patients discharged later. Select patients may be safely discharged earlier. PMID- 26675941 TI - Laparoscopic radical 'no-touch' left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results. AB - BACKGROUND: Laparoscopic left pancreatectomy has been well described for benign pancreatic lesions, but its role in pancreatic adenocarcinoma remains open to debate. We report our results adopting a laparoscopic technique that obeys established oncologic principles of open distal pancreatosplenectomy. METHODS: This is a post hoc analysis of a prospectively kept database of 135 consecutive patients undergoing laparoscopic left pancreatectomy, performed across two sites in the UK and the Netherlands (07/2007-07/2015 Southampton and 10/2013-07/2015 Amsterdam). Primary outcomes were resection margin and lymph node retrieval. Secondary endpoints were other perioperative outcomes, including post-operative pancreatic fistula. Definition of radical resection was distance tumour to resection margin >1 mm. All patients underwent 'laparoscopic radical left pancreatosplenectomy' (LRLP) which involves 'hanging' the pancreas including Gerota's fascia, followed by clockwise dissection, including formal lymphadenectomy. RESULTS: LRLP for pancreatic adenocarcinoma was performed in 25 patients. Seven of the 25 patients (28 %) had extended resections, including the adrenal gland (n = 3), duodenojejunal flexure (n = 2) or transverse mesocolon (n = 3). Mean age was 68 years (54-81). Conversion rate was 0 %, mean operative time 240 min and mean blood loss 340 ml. Median intensive/high care and hospital stay were 1 and 5 days, respectively. Clavien-Dindo score 3+ complication rate was 12 % and ISGPF grade B/C pancreatic fistula rate 28 %; 90-day (or in-hospital) mortality was 0 %. The pancreatic resection margin was clear in all patients, and the posterior margin was involved (<1 mm) in 6 patients, meaning an overall R0 resection rate of 76 %. No resection margin was microscopically involved. Median nodal sample was 15 nodes (3-26). With an average follow-up of 17.2 months, 1 year survival was 88 %. CONCLUSIONS: A standardised laparoscopic approach to pancreatic adenocarcinoma in the left pancreas can be adopted safely. Our study shows that these results can be reproduced across multiple sites using the same technique. PMID- 26675942 TI - Recent Patents on Hypocholesterolemic Therapeutic Strategies: An Update. AB - Worldwide, the cardiovascular diseases constitute a major cause of death with an ever growing incidence. Many medical approaches were developed against this physiopathology and patented; however up to now, no efficient treatment exists. Future developments are not only focusing on the identification of new therapeutic strategies against the cardiovascular diseases but also on a better understanding of the determinants of these multifactorial diseases. In this report, we reviewed the most recent patents that have been reported in this field of research. PMID- 26675944 TI - Arginine 66 Controls Dark-State Formation in Green-to-Red Photoconvertible Fluorescent Proteins. AB - Photoactivated localization microscopy (PALM) is a powerful technique to investigate cellular nanostructures quantitatively and dynamically. However, the use of PALM for molecular counting or single-particle tracking remains limited by the propensity of photoconvertible fluorescent protein markers (PCFPs) to repeatedly enter dark states. By designing the single mutants mEos2-A69T and Dendra2-T69A, we completely swapped the blinking behaviors of mEos2 and Dendra2, two popular PCFPs. We combined X-ray crystallography and single-molecule microscopy to show that blinking in mEos2 and Dendra2 is largely controlled by the orientation of arginine 66, a highly conserved residue in Anthozoan PCFPs. The Arg66 side-chain conformation affects the bleaching and the on-to-off transition quantum yields, as well as the fraction of molecules entering long lived dark states, resulting in widely different apparent blinking behaviors that largely modulate the efficiency of current blinking correction procedures. The present work provides mechanistic insight into the complex photophysics of Anthozoan PCFPs and will facilitate future engineering of bright and low-blinking variants suitable for PALM. PMID- 26675943 TI - Vitamin D/VDR signaling attenuates lipopolysaccharide-induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier. AB - Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)-induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild-type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS-treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P<0.001), increased alveolar permeability [demonstrated by a higher wet-dry ratio of lung weight (P<0.05), greater expression levels of BALF protein (P<0.001) and fluorescein isothiocyanate conjugated 4 kDa dextran (P<0.001) leakage into the alveolar space], elevated proinflammatory cytokine and chemokine mRNA levels, as demonstrated by reverse transcription-quantitative polymerase chain reaction (P<0.05), and decreased protein and mRNA expression levels of occludin (P<0.01) and zonula occludens-1 (ZO-1; P<0.01) compared with WT mice. Paricalcitol treatment partially inhibited these pathological changes in WT mice by maintaining the mRNA and protein expression levels of occludin (P<0.01) and ZO-1 (P<0.05). A lack of VDRs in the pulmonary epithelial barrier appeared to compromise its defense, leading to more severe LPS-induced lung injury. Furthermore, vitamin D treatment alleviated LPS induced lung injury and preserved alveolar barrier function. Therefore vitamin D treatment may present as a potential therapeutic strategy in ALI and acute respiratory distress syndrome. PMID- 26675945 TI - Geriatricians in perioperative medicine: developing subspecialty training. PMID- 26675946 TI - Propofol and food allergy. PMID- 26675947 TI - Transfemoral aortic valve replacement: does anaesthesia make the difference? PMID- 26675948 TI - Clinical recommendations in the management of the patient with type 1 diabetes on insulin pump therapy in the perioperative period: a primer for the anaesthetist. AB - Insulin pump therapy is increasingly common in patients with type 1 diabetes. Many of these patients will require surgery at some point in their lifetime. Few doctors will have experience of managing these patients, and little evidence exists to assist in the development of guidelines for patients with insulin pump therapy, undergoing surgery.It is clear that during emergency surgery insulin pump therapy is not appropriate and should be discontinued, but patients undergoing some elective surgery can and should continue insulin pump therapy, without any adverse effect on their blood sugar control, or on the outcome of their surgery. Individual hospitals need to formalize guidance on the management of patients receiving continuous subcutaneous insulin therapy, to allow patients the choice to continue their therapy during surgery. This expert opinion presents anaesthetists with a suggested clinical framework to help facilitate continued insulin pump therapy, during elective surgery and into the postoperative period. PMID- 26675949 TI - Mortality of emergency general surgical patients and associations with hospital structures and processes. AB - BACKGROUND: Variations in patient outcomes between providers have been described for emergency admissions, including general surgery. The aim of this study was to investigate whether differences in modifiable hospital structures and processes were associated with variance in mortality, amongst patients admitted for emergency colorectal laparotomy, peptic ulcer surgery, appendicectomy, hernia repair and pancreatitis. METHODS: Adult emergency admissions in the English NHS were extracted from the Hospital Episode Statistics between April 2005 and March 2010. The association between mortality and structure and process measures including medical and nursing staffing levels, critical care and operating theatre availability, radiology utilization, teaching hospital status and weekend admissions were investigated. RESULTS: There were 294 602 emergency admissions to 156 NHS Trusts (hospital systems) with a 30-day mortality of 4.2%. Trust-level mortality rates for this cohort ranged from 1.6 to 8.0%. The lowest mortality rates were observed in Trusts with higher levels of medical and nursing staffing, and a greater number of operating theatres and critical care beds relative to provider size. Higher mortality rates were seen in patients admitted to hospital at weekends [OR 1.11 (95% CI 1.06-1.17) P<0.0001], in Trusts with fewer general surgical doctors [1.07 (1.01-1.13) P=0.019] and with lower nursing staff ratios [1.07 (1.01-1.13) P=0.024]. CONCLUSIONS: Significant differences between Trusts were identified in staffing and other infrastructure resources for patients admitted with an emergency general surgical diagnosis. Associations between these factors and mortality rates suggest that potentially modifiable factors exist that relate to patient outcomes, and warrant further investigation. PMID- 26675950 TI - Preoperative abnormalities in serum sodium concentrations are associated with higher in-hospital mortality in patients undergoing major surgery. AB - BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques. RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138 142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium <=137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium >=143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration >=150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality. CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease. PMID- 26675951 TI - Perioperative factors associated with acute kidney injury after partial nephrectomy. AB - BACKGROUND: Partial nephrectomy is performed with the aim to preserve renal function. But the occurrence of postoperative acute kidney injury (AKI) can interfere with this goal. Our primary aim was to evaluate associations between pre-specified modifiable factors and estimated glomerular filtration rate after partial nephrectomy. Our secondary aims were to evaluate associations between pre specified modifiable factors and both serum creatinine concentration and type of nephrectomy. METHODS: The records of 1955 patients who underwent partial nephrectomy were collected. Postoperative estimated glomerular filtration rate (eGFR) was used as the primary outcome measure. Twenty modifiable risk factors were studied. A repeated-measures linear model with autoregressive within-subject correlation structure was used. The interaction between all the factors and type of nephrectomy was also studied. RESULTS: A total of 1187 (61%) patients had no kidney injury, 647 (33%) had stage I, 80 (4%) had stage II, and 41 (2%) had stage III injury. The mean eGFR increased an estimated 0.83 (99.76% CI 0.79-0.88) ml min(-1) 1.73 m(-2) for a unit increase in baseline eGFR. Mean eGFR was 2.65 (99.76% CI: 0.13, 5.18) ml min(-1) 1.73 m(-2) lower in patients with hypertension. Mean eGFR decreased 0.42 (99.76% CI: 0.22, 0.62) ml min(-1) 1.73 m( 2) for a 10-minute longer in duration of procedure and decreased 2.09 (99.76% CI: 1.39, 2.80) ml min(-1) 1.73 m(-2) for a 10-minute longer in ischemia time. It was 3.53 (99.76% CI: 0.83, 6.23) ml min(-1) 1.73 m(-2) lower for patients who received warm ischemia as compared to cold ischemia. CONCLUSION: Potentially modifiable factors associated with AKI in the postoperative period were identified as baseline renal function, preoperative hypertension, longer duration of surgical time and ischaemia time, and warm ischaemia. PMID- 26675952 TI - No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut?. AB - BACKGROUND: Propofol is thought to be a potential cause of allergic reactions in patients allergic to egg, soy or peanut, since current formulations contain an emulsion that includes egg lecithin and soybean oil. However, other than six case reports lacking in confirmatory evidence of an allergic reaction, there is no evidence linking the two types of allergies. The aim of this study was to examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol. METHODS: Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut. RESULTS: Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum. In study B we found no signs of allergic reactions towards propofol in 171 retrieved anaesthetic charts from 99 patients with specific IgE to egg, soy or peanut. CONCLUSION: No connection between allergy to propofol and allergy to egg, soy or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence based and should be reconsidered. PMID- 26675954 TI - Effect of body mass index in acute respiratory distress syndrome. AB - BACKGROUND: Obesity is associated in healthy subjects with a great reduction in functional residual capacity and with a stiffening of lung and chest wall elastance, which promote alveolar collapse and hypoxaemia. Likewise, obese patients with acute respiratory distress syndrome (ARDS) could present greater derangements of respiratory mechanics than patients of normal weight. METHODS: One hundred and one ARDS patients were enrolled. Partitioned respiratory mechanics and gas exchange were measured at 5 and 15 cm H2O of PEEP with a tidal volume of 6-8 ml kg(-1) of predicted body weight. At 5 and 45 cm H2O of PEEP, two lung computed tomography scans were performed. RESULTS: Patients were divided as follows according to BMI: normal weight (BMI<=25 kg m(-2)), overweight (BMI between 25 and 30 kg m(-2)), and obese (BMI>30 kg m(-2)). Obese, overweight, and normal-weight groups presented a similar lung elastance (median [interquartile range], respectively: 17.7 [14.2-24.8], 20.9 [16.1-30.2], and 20.5 [15.2-23.6] cm H2O litre(-1) at 5 cm H2O of PEEP and 19.3 [15.5-26.3], 21.1 [17.4-29.2], and 17.1 [13.4-20.4] cm H2O litre(-1) at 15 cm H2O of PEEP) and chest elastance (respectively: 4.9 [3.1-8.8], 5.9 [3.8-8.7], and 7.8 [3.9-9.8] cm H2O litre(-1) at 5 cm H2O of PEEP and 6.5 [4.5-9.6], 6.6 [4.2-9.2], and 4.9 [2.4-7.6] cm H2O litre(-1) at 15 cm H2O of PEEP). Lung recruitability was not affected by the body weight (15.6 [6.3-23.4], 15.7 [9.8-22.2], and 11.3 [6.2-15.6]% for normal-weight, overweight, and obese groups, respectively). Lung gas volume was significantly lower whereas total superimposed pressure was significantly higher in the obese compared with the normal-weight group (1148 [680-1815] vs 827 [686-1213] ml and 17.4 [15.8-19.3] vs 19.3 [18.6-21.7] cm H2O, respectively). CONCLUSIONS: Obese ARDS patients do not present higher chest wall elastance and lung recruitability. PMID- 26675953 TI - Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery. AB - BACKGROUND: Postoperative cognitive dysfunction (POCD) is common after non cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100beta, neuron specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). METHODS: One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). RESULTS: POCD (>=-1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=-0.14 [95% confidence interval (CI) -0.24 to 0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100beta or NSE concentrations. CONCLUSIONS: Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations. PMID- 26675955 TI - Double-lumen tubes and auto-PEEP during one-lung ventilation. AB - BACKGROUND: Double-lumen tubes (DLT) are routinely used to enable one-lung ventilation (OLV) during thoracic anaesthesia. The flow-dependent resistance of the DLT's bronchial limb may be high as a result of its narrow inner diameter and length, and thus potentially contribute to an unintended increase in positive end expiratory pressure (auto-PEEP). We therefore studied the impact of adult sized DLTs on the dynamic auto-PEEP during OLV. METHODS: In this prospective clinical study, dynamic auto-PEEP was determined in 72 patients undergoing thoracic surgery, with right- and left-sided DLTs of various sizes. During OLV, air trapping was provoked by increasing inspiration to expiration ratio from 1:2 to 2:1 (five steps). Based on measured flow rate, airway pressure (Paw) and bronchial pressure (Pbronch), the pressure gradient across the DLT (DeltaPDLT) and the total auto-PEEP in the respiratory system (i.e. the lungs, the DLT and the ventilator circuit) were determined. Subsequently the DLT's share in total auto-PEEP was calculated. RESULTS: DeltaPDLT was 2.3 (0.7) cm H2O over the entire breathing cycle. At the shortest expiratory time the mean total auto-PEEP was 2.9 (1.5) cm H2O (range 0-5.9 cm H2O). The DLT caused 27 to 31% of the total auto PEEP. Size and side of the DLT's bronchial limb did not impact auto-PEEP significantly. CONCLUSIONS: Although the DLT contributes to the overall auto PEEP, its contribution is small and independent of size and side of the DLT's bronchial limb. The choice of DLT does not influence the risk of auto-PEEP during OLV to a clinically relevant extent. CLINICAL TRIAL REGISTRATION: DRKS00005648. PMID- 26675956 TI - Pharmacological activation of endogenous protective pathways against oxidative stress under conditions of sepsis. AB - BACKGROUND: Mitochondrial oxidative stress has a role in sepsis-induced organ dysfunction. The endogenous mechanisms to initiate protective pathways are controlled by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1alpha) and nuclear factor erythroid 2-like 2 (NFE2L2). Activation of these pathways are potential therapeutic targets in sepsis. We used pharmacological activators to determine the effects on markers of mitochondrial damage and inflammation in human endothelial cells under conditions of sepsis. METHODS: Human endothelial cells were exposed to lipopolysaccharide plus peptidoglycan G to mimic a sepsis environment, with a range of concentrations of a selective synthetic agonist of silent information regulator-1 (SIRT-1) which activates PGC1alpha, or bis(2-hydroxy-benzylidene) acetone (2HBA) which activates NFE2L2, with and without inhibitors of these pathways. Cells were cultured for up to seven days and we measured mitochondrial membrane potential, metabolic activity, and density (as a marker of biogenesis), interkeukin-6 (to reflect inflammation) and glutathione (as a measure of antioxidant status). RESULTS: Under conditions mimicking sepsis, activation of the PGC1alpha and NFE2L2 pathways protected cells from LPS/PepG-induced loss of mitochondrial membrane potential (P=0.0002 and P=0.0009, respectively) and metabolic activity (P=0.05 and P<0.0001, respectively), and dampened interleukin-6 responses (P=0.003 and P=0.0001, respectively). Mitochondrial biogenesis (both P=0.0001) and glutathione (both P<0.0001) were also increased. These effects were blunted by the respective inhibitors. CONCLUSIONS: The development of organ dysfunction during human sepsis is linked to mitochondrial dysfunction, and so activation of PGC1alpha/NFE2L2 is likely to be beneficial. These pathways are attractive therapeutic targets for sepsis. PMID- 26675957 TI - Fitness after chemotherapy. PMID- 26675958 TI - Fasting time: are we now counting calories? PMID- 26675959 TI - Underlying principle of liquid gastric emptying. PMID- 26675960 TI - Early pharmacokinetics of ropivacaine without epinephrine after injection into the psoas compartment. PMID- 26675961 TI - Reply: To PMID 25303987. PMID- 26675962 TI - Percutaneous emergency airway access: prevention, preparation, technique and training. PMID- 26675963 TI - Acute kidney injury after orthotopic liver transplantation. PMID- 26675964 TI - The size of the problem. PMID- 26675965 TI - Reply: acute kidney injury after orthotopic liver transplantation. PMID- 26675966 TI - Difficult intubation in obese patients. PMID- 26675967 TI - Difficult intubation and life-threatening complications in obese patients: understanding the 'environment effect'. PMID- 26675968 TI - Author's reply: To PMID 25431308. PMID- 26675969 TI - Pre-procedure ultrasound as a tool for teaching landmark method for central venous cannulation. PMID- 26675970 TI - Predictors of persistent pain after total knee arthroplasty. PMID- 26675971 TI - Psychological rather than pharmacological interventions for effective prevetion of pain after knee joint replacement? PMID- 26675978 TI - Resveratrol protects cardiomyocytes from doxorubicin-induced apoptosis through the AMPK/P53 pathway. AB - Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 uM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration amplified P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX induced apoptosis via the AMPK/P53 pathway. PMID- 26675979 TI - Brain Activity (fNIRS) in Control State Differs from the Execution and Observation of Object-Related and Object-Unrelated Actions. AB - The authors explored cortical correlates of action execution and observation, directly comparing control condition condition and execution-observation, using functional near-infrared spectroscopy. Transitive actions (meaningful gestures produced in presence of an object) or intransitive actions (meaningful gestures produced in absence of an object) were performed. Increased oxygenated hemoglobin levels were revealed for both action execution and action observation in premotor cortex, and sensorimotor cortex compared to control condition. However, a higher activity in motor areas was observed for action execution than motor observation. In contrast the posterior parietal cortex was similarly activated in case of both execution and observation task. Finally, it was shown that action execution and observation of transitive more than intransitive gestures was supported by similar parietal posterior areas. These findings support the hypothesis of a partial common network for observation and execution of action, and significant implications related to action types (transitive vs. intransitive). PMID- 26675980 TI - Abrupt progression of ventricular septal perforation after primary angioplasty for acute myocardial infarction. AB - A 61-year-old-man was transferred to our hospital because of progressive heart failure after reperfusion for acute myocardial infarction (MI). When he visited the local hospital with severe chest pain associated with inferior MI, transthoracic echocardiography revealed small ventricular septal perforation (VSP). The patient had emergent coronary angiography, which revealed total occlusion of the mid-portion of the right coronary artery. Primary angioplasty was successful for reperfusion. However, because of hemodynamic instability the patient was transferred to our hospital. Under these conditions, transthoracic echocardiography which was undertaken 3 hours after primary angioplasty, demonstrated progressive enlargement of the VSP probably due to reperfusion injury. The rupture site, which was further enlarged at the time of operation, was repaired using the patch exclusion technique. The patient could discharge without complications. We suggest that primary angioplasty may potentially induce late reperfusion injury in patients with VSP complicating MI. PMID- 26675981 TI - Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study. AB - BACKGROUND: A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients (>= 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. RESULTS: In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc alpha-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. CONCLUSION: Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. GENERAL SIGNIFICANCE: This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling. PMID- 26675982 TI - Identification of the TP53-induced glycolysis and apoptosis regulator in various stages of colorectal cancer patients. AB - The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (p<0.01) and stage III (p<0.05) when compared to adjacent normal tissue. Immunohistochemical studies revealed that TIGAR expression was increased in colorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (p<0.05) and late stage (stage III and IV) CRC (p<0.01). TIGAR protein was also found to be highly expressed in stage II and III colorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer. PMID- 26675983 TI - A Retrospective Analysis of Direct Medical Cost and Cost of Drug Therapy in Hospitalized Patients at Private Hospital in Western India. AB - BACKGROUND: Pharmacoeconomics is analytical tool to know cost of hospitalization and its effect on health care system and society. In India, apart from the government health services, private sector also play big role to provide health care services. OBJECTIVE: To study the direct medical cost and cost of drug therapy in hospitalized patients at private hospital. MATERIALS AND METHODS: A retrospective study was conducted at private hospital in a metro city of Western India. Total 400 patients' billing records were selected randomly for a period from 01/01/2013 to 31/12/2014. Data were collected from medical record of hospital with permission of medical director of hospital. Patients' demographic profile age, sex, diagnosis and various costs like ICU charge, ventilator charge, diagnostic charge, etc. were noted in previously formed case record form. Data were analysed by Z, x(2) and unpaired t-test. RESULT: Patients were divided into less than 45 years and more than 45 year age group. They were divided into medical and surgical patients according to their admission in medical or surgical ward. Mortality, Intensive Care Unit (ICU) admission, patients on ventilator were significantly (p<0.05) higher in medical patients. Direct medical cost, ward bed charge, ICU bed charge, ventilator charge and cost of drug therapy per patient were significantly (p<0.05) higher in medical patients while operation theatre and procedural charge were significantly (p<0.05) higher in surgical patients. Cost of fibrinolytics, anticoagulants, cardiovascular drugs were significantly (p<0.05) higher in medical patients. Cost of antimicrobials, proton pump inhibitors (PPIs), antiemetics, analgesics, were significantly (p<0.05) higher in surgical patients. CONCLUSION: Ward bed charge, ICU bed charge, ventilator charge accounted more than one third cost of direct medical cost in all the patients. Cost of drug therapy was one fourth of direct medical cost. Antimicrobials cost accounted 33% of cost of drug therapy. PMID- 26675984 TI - Nerve growth factor and its receptor in schizophrenia. AB - Promising studies suggest that defects in synaptic plasticity detected in schizophrenia may be linked to neurodevelopmental and neurodegenerative abnormalities and contribute to disease-associated cognitive impairment. We aimed to clarify the role of the synaptic plasticity regulatory proteins, nerve growth factor (NGF) and its receptor (NGFR) in the pathogenesis of schizophrenia by comparative analysis of their blood levels and functional single nucleotide polymorphisms (SNPs) in genes encoding these proteins (NGF and NGFR) in schizophrenia-affected and healthy subjects. Relationships between the selected SNPs' genotypes and NGF and NGFR plasma levels were also assessed. Our results demonstrated a positive association between schizophrenia and the NGF rs6330 as well as the NGFR rs11466155 and rs2072446 SNPs. Also, a negative association between this disorder and NGF rs4839435 as well as NGFR rs734194 was found. In both, haloperidol-treated and antipsychotic-free patients decreased blood levels of the NGF and NGFR were found, and a positive interrelation between rs6330 and rs2072446 carriage and decreased NGF and NGFR levels, respectively, was revealed. In conclusion, our results demonstrate association of schizophrenia with the rs6330, rs4839435 and rs734194, rs11466155, rs2072446 as well as with the decreased blood levels of corresponding proteins. Our findings indicate the implication of alterations in NGFR and NGFR genes in schizophrenia, particularly, in defects of synaptic plasticity. Furthermore, the data obtained suggests that at least in Armenian population the NGF rs6330*T and NGFR rs11466155*T, rs2072446*T alleles might be nominated as risk factors, whereas the NGF rs4839435*A and NGFR rs734194*G alleles might be protective against developing schizophrenia. PMID- 26675985 TI - Structural Characteristics Are Not Associated With Pain and Function in Rotator Cuff Tears: The ROW Cohort Study. AB - BACKGROUND: Structural characteristics of rotator cuff tears are used in surgical decision making. However, data on the association of tear size with patient reported pain and function are sparse. PURPOSE: To assess the association of tear size, fatty infiltration, and muscle atrophy with shoulder pain/function in patients with cuff tears undergoing operative and nonoperative treatment. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 67 patients with rotator cuff tears were recruited for this longitudinal cohort study. Patients were determined to have a cuff tear using clinical assessment and blinded magnetic resonance imaging review. The Shoulder Pain and Disability Index (SPADI) was used as a measure of shoulder pain and function. RESULTS: Tear size and thickness were not significantly associated with pain (SPADI pain score, 60.6 [95% CI, 49.8-71.5] for partial-thickness tear; 56.8 [95% CI, 42.8-70.7] for <2 cm full-thickness tear; 60.4 [95% CI, 51.7-69.0] for >=2 cm full-thickness tear). Tear size and thickness were not associated with function (SPADI disability score, 42.7 [95% CI, 29.8-55.6] for partial-thickness tear; 37.6 [95% CI, 23.9 51.4] for <2 cm full-thickness tear; 45.1 [95% CI, 35.4-54.8] for >=2 cm full thickness tear). Fatty infiltration, muscle atrophy, and tendon retraction were also not significantly associated with SPADI pain and disability scores. A Mental Health Index score of <68 as well as age >=60 years were significantly associated with a higher SPADI pain score. Female sex, increased number of comorbidities, Mental Health Index score of <68, and age <60 years were significantly associated with a higher SPADI disability score. CONCLUSION: In patients with rotator cuff tears undergoing operative and nonoperative treatment, pain and functional status were not associated with tear size and thickness, fatty infiltration, and muscle atrophy. Conversely, factors unrelated to cuff anatomy such as mental health, comorbidities, age, and sex were associated with pain/function. These findings have clinical implications during surgical decision making and suggest that pain and functional disability in patients with rotator cuff tears is multifactorial and should not solely be attributed to structural characteristics. PMID- 26675986 TI - Preparation and application of cellulose acetate/Fe films in the degradation of Reactive Black 5 dye through photo-Fenton reaction. AB - In this study, the Reactive Black 5 dye degradation and textile effluent were investigated using the photo-Fenton process employing immobilized Fe(3+) in acetate cellulose films. The films prepared were characterized through Fourier transform infrared spectroscopy, atomic absorption spectroscopy, scanning electron microscopy - energy-dispersive spectroscopy and ultraviolet visible spectroscopy. The factorial design revealed that the best conditions for the Reactive Black 5 dye degradation were obtained using the film containing 5% Fe (w/w), 100 mg L(-1) H2O2 and pH 4.0. In studies using artificial light, the dye degradation was 99.29% and the chemical oxygen demand (COD) reduction was 90% after 45 min of treatment. In the process assisted by sunlight, the degradation was 86% and the COD reduction was 70% considering the same time of treatment. At pH 6.0 and artificial light, the dye degradation was 98.90% and the COD reduction was 78%, indicating that the material prepared can be used at pH values greater than 3 without the occurrence of hydrated ferric oxides precipitation. It was also observed that the material can be reused seven consecutive times without substantial loss of efficacy in dye degradation. Furthermore, the proposed material reduces the COD of a textile effluent by 72% after 300 min of treatment. PMID- 26675987 TI - Surface Chemically Switchable Ultraviolet Luminescence from Interfacial Two Dimensional Electron Gas. AB - We report intense, narrow line-width, surface chemisorption-activated and reversible ultraviolet (UV) photoluminescence from radiative recombination of the two-dimensional electron gas (2DEG) with photoexcited holes at LaAlO3/SrTiO3. The switchable luminescence arises from an electron transfer-driven modification of the electronic structure via H-chemisorption onto the AlO2-terminated surface of LaAlO3, at least 2 nm away from the interface. The control of the onset of emission and its intensity are functionalities that go beyond the luminescence of compound semiconductor quantum wells. Connections between reversible chemisorption, fast electron transfer, and quantum-well luminescence suggest a new model for surface chemically reconfigurable solid-state UV optoelectronics and molecular sensing. PMID- 26675988 TI - Unusual Complication of Surgical Abortion with Pelvic Extrusion of Fetal Head: A Case Report. AB - Unsafe abortion is one of the causes of maternal mortality and morbidity in developing countries. The complications mostly results following unsafe abortion procedure done by unskilled provider with or without minimal medical knowledge in rural part of developing countries. These complications can endanger the life of mother if proper medical or surgical interventions are not offered in time. A majority of these complications remains confidential. The uterine perforation is one of the serious but preventable complications of surgical abortion. A 21-year old woman G4P2L2A1, presented in the emergency ward with complaints of lower abdominal pain for four days after attempting twice surgical termination of pregnancy at 19 weeks of gestation for an unwanted pregnancy. Transabdominal sonography and MRI revealed uterine rent with pelvic extrusion of fetal head. Emergency laparotomy with removal of fetal head and uterine rent repair was done. This case illustrates the importance of maintaining a high index of suspicion by the gynaecologist for uterine perforation in patient presenting with abdominal pain a few days after undergoing surgical abortion, also shows the complementary role of sonography and MRI in evaluation of the similar patient and this case also highlights the rampant illegal unsafe abortion procedure in rural India despite of legalization of abortion act. PMID- 26675989 TI - Joining the patient on the path to customized prophylaxis: one hemophilia team explores the tools of engagement. AB - BACKGROUND: The relationship between hemophilia team interventions and achievement of optimal clinical outcomes remains to be elucidated. The British Columbia Hemophilia Adult Team has previously reported results of a comprehensive approach to individualize prophylaxis that has resulted in substantially reduced bleeding rates. In order to facilitate knowledge exchange and potential replication, it was important to gain a thorough understanding of the team's approach. METHODS: A focus group of the British Columbia Hemophilia Adult Team was conducted to identify specific roles and processes that might be contributing to the prophylaxis regimen outcomes in this clinic. The focus group consisted of two workshops; one to describe the individual and collective roles of the clinic team in providing clinical care and guiding patients toward individualized prophylaxis; and the other to describe the patient journey from initial contact through reaching a successful engagement with the clinic. RESULTS: Analysis of the results revealed team roles and processes that underpinned a shared decision making relationship with the patient with a particular focus on supporting the patient's autonomy. Within this relationship, team focus shifts away from "adherence" toward the process whereby patients design and implement prophylaxis regimens resulting in reduction or elimination of bleeding episodes. LIMITATIONS: Using the current methodology, it is not possible to demonstrate a causal link between specific team processes and improved bleeding rates in patients. CONCLUSION: Through the active support of patient autonomy in all aspects of decisions related to hemophilia management, the British Columbia Hemophilia Adult Team approach de-emphasizes "adherence" as the primary goal, and focuses on a prophylaxis plan that is customized by the patient and aligned with his priorities. Adoption of this comprehensive team approach facilitates shared goals between the patient and the team that may optimize treatment adherence, but more importantly, reduce bleeding rates. PMID- 26675990 TI - Colon-Cut-off-Sign in the CT-Scanogram - Evidence of Pancreatitis? AB - One of the less considered but radiologically characteristic signs in conventional radiographic imaging of the abdomen in acute pancreatitis is the so called colon-cut-off-sign. This sign refers to the abrupt termination of gas filling of the colon at the level of the left flexure. The more distal part of the colon usually shows a markedly reduced or a lack of gas filling. This bowel gas distribution, which feigns a constriction of the colon at the left flexure, has been observed within the context of acute pancreatitis for over 50 years. The frequency and sensitivity of the Colon-cut-off-sign fluctuate considerably in different studies. It can also be demonstrated in computed tomography (CT) and in the retrograde contrast medium filling of the colon. We report on a patient who was admitted to the department of internal medicine with pronounced, progressive upper abdominal pain, combined with fever, elevated CRP, lipase and amylase, and leukocytosis, with suspected pancreatitis. Colonoscopy was interrupted due to stenosis in the area of the left flexure, a stenosing tumour being suspected. Over the course of further diagnostics, the scanogram of the abdominal CT already showed a colon-cut-off-sign. In addition, exudative pancreatitis with a stenosing process in the area of the left colonic flexure was found. A solid tumour could be ruled out in repeated endoscopy. PMID- 26675991 TI - Hepatocellular Carcinoma: Basic and Transitional Research. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths worldwide. The outcome of HCC therapy depends on the stage of HCC. Early-stage HCC patients can be cured with radical treatment approaches, whereas no standard treatment regimens can be recommended for patients with advanced disease. SUMMARY: In-depth basic research into the molecular mechanisms of HCC has contributed to the development of novel therapeutic agents. This article reviews several key classes of novel therapeutic agents that are under development, including molecular-targeted therapies, cancer stem cell (CSC)-based therapy and differentiation therapy. KEY MESSAGE: A greater understanding of the molecular pathogenesis of HCC has contributed to the development of novel therapeutic agents. This article reviews several key classes of novel therapeutic agents that are under development, including molecular-targeted therapies, CSC based therapy and differentiation therapy. PRACTICAL IMPLICATIONS: Molecular targeted therapies based on signaling pathways involved in hepatocarcinogenesis and progression are being evaluated in several clinical trials. There are three main categories of targeted agents: tyrosine kinase inhibitors (TKIs), monoclonal antibodies and enzyme inhibitors. The best-established agent is sorafenib, a non specific TKI that is accepted as first-line therapy for specific patients. Other similar agents under investigation include erlotinib, linifanib and brivanib. CSC based therapies are still in the earlier stages of development and include a neutralizing anti-CD44 antibody, small interfering RNA to suppress epithelial cell adhesion molecular levels, a neutralizing anti-CD13 antibody and a CD13 inhibitor. An important point is that CSC-targeted therapy should be combined with conventional therapies to achieve complete tumor regression. Differentiation therapy is defined as a strategy that induces malignant reversion of tumor cells. Hepatocyte nuclear factor 4alpha or 1alpha, important transcriptional factors for hepatocyte differentiation and phenotype maintenance, have shown significant antitumor effects by inducing differentiation of both non-CSCs and CSCs in HCC towards a hepatocyte-like phenotype. PMID- 26675992 TI - Standards of the Polish Ultrasound Society - update. Sonography of the lower extremity veins. AB - This article has been prepared on the basis of the Ultrasonography Standards of the Polish Ultrasound Society (2011) and updated based on the latest findings and reports. Ultrasound examination of the lower extremity veins is relatively easy and commonly used to confirm or rule out venous thrombosis. However, a relatively easy compression test frequently requires experience, particularly in situations when imaging is difficult (due to lymphedema, dressing or thick tissues). The technique is time-consuming and requires assessment of each deep vein every 1 cm. Lesions in the deep veins cannot be ruled out when the vessels are assessed in only 2-3 points - a full examination is needed. The value of the method is the highest when the proximal section is assessed and the lowest when crural veins are evaluated. Doppler sonography is the basic method used when patients are prepared for a surgery of varicose veins. The assessment of the superficial veins prior to this procedure is tedious and requires knowledge of anatomy together with numerous variants. A considerable challenge is posed by re-assessment of recurrent varicose veins following a previous surgery. The Standards include anatomic nomenclature proposed by the Polish Society for Vascular Surgery and Polish Society of Phlebology, which should facilitate communication with clinicians. The most beneficial patient positions have been thoroughly discussed in terms of safety and effectiveness of the examination. Sometimes during such an examination, no venous pathology is found, but other changes with symptoms that suggest deep thrombophlebitis are detected. In such a situation, it is necessary to conduct an initial (or complete, if possible) assessment of lesions as well as provide recommendations connected with further, more detailed diagnosis. PMID- 26675993 TI - [Creating a new table of occupational diseases for burnout is not a good answer to prevent it]. PMID- 26675994 TI - Contrast enhanced ultrasound of sentinel lymph nodes. AB - Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient's prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal "avascular" areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue((r)), Sonazoid((r)) and Definity((r)). This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node. PMID- 26675995 TI - Diffuse lymphatic leakage after continuous vacuum-assisted closure therapy for thoracic wound infection after rib stabilization. AB - Vacuum-assisted closure (VAC) therapy is a useful tool in the management of a wide spectrum of complex wounds in cardiothoracic surgery. It promotes healing through the application of a controlled and localized negative pressure on porous polyurethane absorbent foams. Known advantages of the VAC therapy are the acceleration of wound healing, stimulation of granulation tissue and reduced tissue edema. Despite its excellent properties, some related complications after and during the therapy have been reported. We report the case of a 47-year-old female with a thoracic wound infection after rib stabilization, managed with open surgery and VAC therapy, which was complicated by a diffuse lymphatic leakage. This is the first case described of diffuse lymphatic leakage followed by partial necrosis of the breast after continuous VAC therapy. We recommend the application of a lower pressure level of this device for complex wounds of the chest wall near the breast. PMID- 26675996 TI - The advantages of combining sonotopogram with indication and fixation in invasive ultrasound. AB - The usefulness of sonotopogram, that is mapping of the operated area basing on ultrasound, is obvious and currently unquestionable. It is performed in order to improve safety level of a patient treated by means of invasive techniques. It constitutes an excellent complement of the Perioperative Control Card. At the beginning it was used in sonosurgical procedures, with time it has become an element of all surgical techniques. It undergoes multiple changes depending on the surgeon's needs. A particularly interesting phenomenon is the combination of the invasive techniques in order to facilitate the performance of medical procedures. Because of some relationship we are going to present the combination of sonotopogram with fixation and indication techniques. They are puncture techniques which are relatively rarely used in invasive ultrasound and surgical procedures. It seems that this results from the ignorance of their potential and the technique of their performance. Great simplicity makes them universal and allows to combine them freely. This simple combinations can be extended practically endlessly - similarly to domino bricks. For example, the next element of the technique combining can be the removal of an indicated and fixated element or a nailing. It is an excellent example of the complementarity rule - it should facilitate the understanding of Allin1 techniques and sonosurgery and also help in everyday practice of doctors performing invasive procedures. The use of these methods should be propagated not only in ultrasound but also in everyday medical practice in all the specialties. The presentation of the examples of particular techniques and their combination enables to bring closer their practical use. PMID- 26675997 TI - SWAT meta-modeling as support of the management scenario analysis in large watersheds. AB - In the last two decades, numerous models and modeling techniques have been developed to simulate nonpoint source pollution effects. Most models simulate the hydrological, chemical, and physical processes involved in the entrainment and transport of sediment, nutrients, and pesticides. Very often these models require a distributed modeling approach and are limited in scope by the requirement of homogeneity and by the need to manipulate extensive data sets. Physically based models are extensively used in this field as a decision support for managing the nonpoint source emissions. A common characteristic of this type of model is a demanding input of several state variables that makes the calibration and effort costing in implementing any simulation scenario more difficult. In this study the USDA Soil and Water Assessment Tool (SWAT) was used to model the Venice Lagoon Watershed (VLW), Northern Italy. A Multi-Layer Perceptron (MLP) network was trained on SWAT simulations and used as a meta-model for scenario analysis. The MLP meta-model was successfully trained and showed an overall accuracy higher than 70% both on the training and on the evaluation set, allowing a significant simplification in conducting scenario analysis. PMID- 26675998 TI - Sanitising black water by auto-thermal aerobic digestion (ATAD) combined with ammonia treatment. AB - The effect of a two-step process on the concentration of pathogens and indicator microorganisms in black water (0.9-1% total solids) was studied. The treatment combined auto-thermal aerobic digestion (ATAD) and ammonia sanitisation. First, the temperature of the black water was increased through ATAD and when a targeted temperature was reached (33, 41 and 45.5 degrees C studied), urea was added to a 0.5% concentration (total ammonia nitrogen >2.9 g L-1). Escherichia coli and Salmonella spp. were reduced to non-detectable levels within 3 days following urea addition at temperatures above 40 degrees C, whereas when urea was added at 33 degrees C E. coli was still present after 8 days. By adding urea at temperatures of 40 degrees C and above, a 5 log10 reduction in Enterococcus spp. and a 3 log10 reduction in Ascaris suum eggs was achieved 1 week after the addition. With combined ATAD and ammonia treatment using 0.5% ww urea added at an aerobic digestion temperature >40 degrees C, black water was sanitised regarding the pathogens studied in 2 weeks of total treatment time. PMID- 26675999 TI - Efficient visible-light photocatalytic degradation of sulfadiazine sodium with hierarchical Bi7O9I3under solar irradiation. AB - Bi7O9I3, a kind of visible-light-responsive photocatalyst, with hierarchical micro/nano-architecture was successfully synthesized by oil-bath heating method, with ethylene glycol as solvent, and applied to degrade sulfonamide antibiotics. The as-prepared product was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflection spectra and scanning electron microscopy (SEM). XRD and XPS tests confirmed that the product was indeed Bi7O9I3. The result of SEM observation shows that the as-synthesized Bi7O9I3 consists of a large number of micro-sheets with parallel rectangle structure. The optical test exhibited strong photoabsorption in visible light irradiation, with 617 nm of absorption edges. Moreover, the difference in the photocatalytic efficiency of as-prepared Bi7O9I3 at different seasons of a whole year was investigated in this study. The chemical oxygen demand removal efficiency and concentration of NO(3)(-) and SO(4)(2-) of solution after reaction were also researched to confirm whether degradation of the pollutant was complete; the results indicated a high mineralization capacity of Bi7O9I3. The as synthesized Bi7O9I3exhibits an excellent oxidizing capacity of sulfadiazine sodium and favorable stability during the photocatalytic reaction. PMID- 26676000 TI - Mixed micelles-mediated dephenolisation of table olive processing's wastewaters. AB - Olive processing wastewaters account for highly pollutant agro-industrial effluents. Their phenolic compounds are responsible for their toxicity. Those natural compounds have to be degraded or recovered before any discharge into the environment. This investigation deals with the extraction and concentration of the phenolic compounds into an aqueous phase using a mixture of nonionic/anionic surfactants. A synergistic effect for the extraction of the natural phenolic compounds was observed when Genapol X-80 was combined with sodium dodecyl sulphate (SDS). For the tested Genapol X-80 concentration (1-5%), a minimum concentration of 2.5 mM SDS was demonstrated to be necessary to reach maximum extraction rates. The extraction efficiencies were only slightly affected by temperatures between 20 and 50 degrees C. However, the recovery rate of the phenolic compounds increased with the augmentation of the contact time. The pH has also been found to greatly influence the extraction of the phenolic compounds and the coacervate volume fraction. At optimal conditions, the coacervate phase was enriched up to four times whereas the maximum reduction of the phenolic content in the diluted phase reached more than 40% in one step extraction. PMID- 26676001 TI - Anaerobic digestion of post-hydrothermal liquefaction wastewater for improved energy efficiency of hydrothermal bioenergy processes. AB - Hydrothermal liquefaction (HTL) is a promising process for converting wet biomass and organic wastes into bio-crude oil. It also produces an aqueous product referred to as post-hydrothermal liquefaction wastewater (PHWW) containing up to 40% of the original feedstock carbon, which reduces the overall energy efficiency of the HTL process. This study investigated the feasibility of using anaerobic digestion (AD) to treat PHWW, with the aid of activated carbon. Results showed that successful AD occurred at relatively low concentrations of PHWW (<= 6.7%), producing a biogas yield of 0.5 ml/mg CODremoved, and ~53% energy recovery efficiency. Higher concentrations of PHWW (>=13.3%) had an inhibitory effect on the AD process, as indicated by delayed, slower, or no biogas production. Activated carbon was shown to effectively mitigate this inhibitory effect by enhancing biogas production and allowing digestion to proceed at higher PHWW concentrations (up to 33.3%), likely due to sequestering toxic organic compounds. The addition of activated carbon also increased the net energy recovery efficiency of AD with a relatively high concentration of PHWW (33.3%), taking into account the energy for producing activated carbon. These results suggest that AD is a feasible approach to treat PHWW, and to improve the energy efficiency of the HTL processes. PMID- 26676002 TI - Nitrogen removal using an anammox membrane bioreactor at low temperature. AB - Membrane bioreactors (MBRs) have the ability to completely retain biomass and are thus suitable for slowly growing anammox bacteria. In the present study, an anammox MBR was operated to investigate whether the anammox activity would remain stable at low temperature, without anammox biomass washout. The maximum nitrogen removal rates were 6.7 and 1.1 g-N L-1 day-1 at 35 degrees C and 15 degrees C, respectively. Fluorescence in situ hybridization and 16S rRNA-based phylogenetic analysis revealed no change in the predominant anammox species with temperature because of the complete retention of anammox biomass in the MBR. These results indicate that the predominant anammox bacteria in the MBR cannot adapt to a low temperature during short-term operation. Conversely, anammox activity recovered rapidly after restoring the temperature from the lower value to the optimal temperature (35 degrees C). The rapid recovery of anammox activity is a distinct advantage of using an MBR anammox reactor. PMID- 26676003 TI - Removal of Cu(II) and Ni(II) ions from an aqueous solution using alpha Fe2O3nanoparticle-coated volcanic rocks. AB - An adsorbent, volcanic rocks coated with alpha-Fe2O3nanoparticles, was prepared and utilized for the removal of Cu(II) and Ni(II) ions from an aqueous solution. Characterization of the coated volcanic rocks indicated that the alpha Fe2O3nanoparticles were successfully and homogeneously distributed on the volcanic rocks, including penetration into rock pores. Batch experiments were conducted to investigate adsorption performance. The adsorption behavior of both ions was found to best fit a pseudo second-order model and Langmuir isotherm. The maximum adsorption capacities of Cu(II) and Ni(II) ions were 58.14 mg g-1 and 56.50 mg g-1 at 293 K, respectively, and increased with rising temperature. The loaded alpha-Fe2O3nanoparticles onto volcanic rock significantly increased removal of Cu(II) and Ni(II) ions. The adsorption process was combined control of film diffusion and intra-particle diffusion. Adsorption thermodynamics indicated the adsorption process was spontaneous and occurred mainly through chemisorption. The results confirmed that the volcanic rocks coated with alpha Fe2O3nanoparticles acted as a high-efficiency and low-cost absorbent, and effectively removed Cu(II) and Ni(II) from wastewater. PMID- 26676005 TI - Granular ferric hydroxide adsorbent for phosphate removal: demonstration preparation and field study. AB - Ferric hydroxide (FHO), which has high phosphate adsorption capacity, was prepared by precipitation at industrial scale and then fabricated via the drum granulation method with cross-linked poly(vinyl alcohol) as the binder. The optimum binder/FHO powder ratio was 0.6 for producing a granular adsorbent with a high phosphate adsorption capacity and stability. The Langmuir maximum adsorption capacities of powder and granular FHOs were 74.07 mg g-1 and 56.18 mg g(-1) at pH 7.0 +/- 0.2, respectively, which were higher than those of other reported phosphate adsorbents under neutral or acidic conditions. Phosphate-loaded granular FHO could be regenerated by NaOH solution. Columns containing the granular FHO were used for phosphate removal from ozonated secondary effluents of a municipal wastewater treatment plant at space velocity (SV) of 2 and 5 h-1. During more than 2 months' operation, the average removal percentage of PO(4)(3-) was more than 90% and the turbidity and concentration of CODMn in the effluents were lower than in the influents. In addition, energy dispersive X-ray results suggested that active sites inside the granular FHO were available for phosphate removal. The results demonstrated that granular FHO can be applied as an assist technology for phosphate removal from secondary effluents. PMID- 26676004 TI - Aluminosilicate-based adsorbent in equimolar and non-equimolar binary-component heavy metal removal systems. AB - Cadmium (Cd) and lead (Pb) are toxic heavy metals commonly used in various industries. The simultaneous presence of these metals in wastewater amplifies the toxicity of wastewater and the complexity of the treatment process. This study has investigated the selective behavior of an aluminosilicate-based mesoporous adsorbent. It has been demonstrated that when equimolar quantities of the metals are present in wastewater, the adsorbent uptakes the Pb2+ ions selectively. This has been attributed to the higher electronegativity value of Pb2+ compared to Cd2+ which can be more readily adsorbed on the adsorbent surface, displacing the Cd2+ ions. The selectivity can be advantageous when the objective is the separation and reuse of the metals besides wastewater treatment. In non-equimolar solutions, a complete selectivity can be observed up to a threshold Pb2+ molar ratio of 30%. Below this threshold value, the Cd2+ and Pb2+ ions are uptaken simultaneously due to the abundance of Cd2+ ions and the availability of adsorption sites at very low Pb2+ molar ratios. Moreover, the total adsorption capacities of the adsorbent for the multi-component system have been shown to be in the same range as the single-component system for each metal ion which can be of high value for industrial applications. PMID- 26676006 TI - Effects of physical and morphometric factors on nutrient removal properties in agricultural ponds. AB - Effects of physical and morphometric factors on nutrient removal properties were studied in small agricultural ponds with different depths, volumes, and residence times in western Japan. Average residence time was estimated to be >15 days, and it tended to decrease from summer to winter because of the increase in water withdrawal for agricultural activity. Water temperature was clearly different between the surface and bottom layers; this indicates that thermal stratification occurred in summer. Chlorophyll-a was significantly high (>20 MUg/L) in the surface layer (<0.5 m) and influenced by the thermal stratification. Removal ratios of dissolved total nitrogen (DTN) and dissolved total phosphorus in the ponds were estimated to be 53-98% and 39-98% in August and 10-92% and 36-57% in December, respectively. Residence time of the ponds was longer in August than in December, and DTN removal, in particular, was more significant in ponds with longer residence time. Our results suggest residence time is an important factor for nitrogen removal in small agricultural ponds as well as large lakes. PMID- 26676007 TI - Application of the QUAL2K model to design an ecological purification scheme for treated effluent of a wastewater treatment plant. AB - Treated effluent from wastewater treatment plants has become an important source of excess nutrients causing eutrophication in water. In this study, an ecological purification method was used to further treat eutrophic water. A three-season ecological purification scheme which comprised an emergent plant (Eme.), a submerged plant (Sub.) and a novel biological rope (Bio.), was designed for the treated effluent canal of a wastewater treatment plant. The removal parameters determined from the experiment were input into a QUAL2K model to simulate downstream water quality of the treated effluent canal. Respective removal rates of total nitrogen and total phosphorus of the Eme., Sub. and Bio. were 32.48 37.33% and 31.63-39.86% in summer, 14.12-33.61% and 17.74-23.80% in autumn, and 14.13-18.03% and 10.05-12.75% in winter, with 1-day reaction time. Optimal combinations for summer, autumn/spring, and winter are Eme. + Bio., Eme. + Bio. + Sub., and Sub. + Bio., respectively. Simulated load reduction rates of total nitrogen and total phosphorus for the treated effluent canal were 42.64-78.40% and 30.98-78.29%, respectively, year round with 2.5-day reaction time. This study provides an efficient evaluation and design method for ecological purification engineering. PMID- 26676008 TI - Greywater reuse through a bioretention system prototype in the arid region. AB - The concept of a greywater-fed bioretention system in arid regions was investigated in this study. Bioretention systems are conventionally used as a source control mechanism for urban runoff. Nevertheless, in arid regions, where rain and urban runoff are not an abundant water resource, their application is limited. Greywater (residential wastewater without toilet and kitchen sources) is comparatively less polluted and has the potential for reuse in irrigation and non potable water uses. However, selection of an appropriate treatment is a challenge. A prototype bioretention system was made and its ability to improve greywater quality was monitored for more than 10 consecutive days. A vegetative and non-vegetative system were monitored separately. After 24 hours of retention in both systems, greywater quality was improved significantly. Both systems performed almost equally well; however, the vegetative system (with canary reed grass, Phalaris arundinacea) was found to be more effective in reducing the sodium and chemical oxygen demand contents. The study revealed that the concept of the greywater-fed bioretention system has the potential to add multi functional benefits (greywater treatment, water conservation, landscape aesthetic and biodiversity) to the arid regions' urban environment. PMID- 26676009 TI - Agricultural biomass monitoring on watersheds based on remotely sensed data. AB - There is a close quality relationship between the harmful levels of all three drought indicator groups (meteorological, hydrological and agricultural). However, the numerical scale of the relationships between them is unclear and the conversion of indicators is unsolved. Different areas or an area with different forms of drought cannot be compared. For example, from the evaluation of meteorological drought using the standardized precipitation index (SPI) values of a river basin, it cannot be stated how many tonnes of maize will be lost during a given drought period. A reliable estimated rate of yield loss would be very important information for the planned interventions (i.e. by farmers or river basin management organisations) in terms of time and cost. The aim of our research project was to develop a process which could provide information for estimating relevant drought indexes and drought related yield losses more effectively from remotely sensed spectral data and to determine the congruency of data derived from spectral data and from field measurements. The paper discusses a new calculation method, which provides early information on physical implementation of drought risk levels. The elaborated method provides improvement in setting up a complex drought monitoring system, which could assist hydrologists, meteorologists and farmers to predict and more precisely quantify the yield loss and the role of vegetation in the hydrological cycle. The results also allow the conversion of different-purpose drought indices, such as meteorological, agricultural and hydrological ones, as well as allow more water saving agricultural land use alternatives to be planned in the river basins. PMID- 26676010 TI - Improve bio-activity of anaerobic sludge by low energy ultrasound. AB - This research focused on ultrasound-enhanced bio-activity of anaerobic sludge. Low energy ultrasound irradiation can increase the bio-activity of anaerobic sludge. Ultrasonic parameter, characteristics of anaerobic sludge and experimental conditions are important parameters which affect the enhancement effect on anaerobic sludge. In order to assess the effects of characteristics of anaerobic sludge and experimental conditions on ultrasonic irradiation of anaerobic sludge, experiments with different characteristics of anaerobic sludge were carried out and analyzed with the content of coenzyme F420 and dehydrogenase activity (DHA). The results showed that anaerobic sludge bio-activity was impacted by the initial temperature, initial chemical oxygen demand (COD), sludge concentration, and stirring during the ultrasonic process. Optimal performance was achieved when sound frequency, power density, and ultrasonic irradiation period was 20 kHz, 0.1 W/mL, and 10 min, respectively, under which the wastewater COD removal efficiency was increased by 12.9 percentage points. The results indicated that low temperature could affect the anaerobic sludge irradiation effect, while intermittent stirring could enhance the bio-activity of anaerobic sludge irradiation effect and low substrate concentration improved anaerobic sludge activity by ultrasound. PMID- 26676011 TI - Kinetics and equilibrium adsorption study of p-nitrophenol onto activated carbon derived from walnut peel. AB - An original activated carbon prepared from walnut peel, which was activated by zinc chloride, was modified with ammonium hydroxide or sodium hydroxide in order to contrast the adsorption property of the three different activated carbons. The experiment used a static adsorption test for p-nitrophenol. The effects of parameters such as initial concentration, contact time and pH value on amount adsorbed and removal are discussed in depth. The thermodynamic data of adsorption were analyzed by Freundlich and Langmuir models. The kinetic data of adsorption were measured by the pseudo-first-order kinetics and the pseudo-second-order kinetics models. The results indicated that the alkalized carbon samples derived from walnut peel had a better performance than the original activated carbon treated with zinc chloride. It was found that adsorption equilibrium time was 6 h. The maximum removal rate of activated carbon treated with zinc chloride for p nitrophenol was 87.3% at pH 3,whereas the maximum removal rate of the two modified activated carbon materials was found to be 90.8% (alkalized with ammonium hydroxide) and 92.0% (alkalized with sodium hydroxide) at the same pH. The adsorption data of the zinc chloride activated carbon were fitted to the Langmuir isotherm model. The two alkalized activated carbon samples were fitted well to the Freundlich model. The pseudo-second-order dynamics equation provided better explanation of the adsorption dynamics data of the three activated carbons than the pseudo-first-order dynamics equation. PMID- 26676012 TI - Nitrite reduction and methanogenesis in a single-stage UASB reactor. AB - In this study, nitrite reduction and methanogenesis in a single-stage upflow anaerobic sludge blanket (UASB) reactor was investigated, using high-strength synthetic domestic wastewater as substrate. To assess long-term effects and evaluate the mechanisms that allow successful nitrite reduction and methanogenesis in a single-stage UASB, sludge was exposed to relatively high nitrite loading rates (315 +/- 13 mgNO(2)(-)-N/(l.d)), using a chemical oxygen demand (COD) to nitrogen ratio of 18 gCOD/gNO(2)(-)-N, and an organic loading rate of 5.4 +/- 0.2 gCOD/(l.d). In parallel, the effects of sludge morphology on methanogenesis inhibition were studied by performing short-term batch activity tests at different COD/NO(2)(-)-N ratios with anaerobic sludge samples. In long term tests, denitrification was practically complete and COD removal efficiency did not change significantly after nitrite addition. Furthermore, methane production only decreased by 13%, agreeing with the reducing equivalents requirement for complete NO(2)(-) reduction to N2. Apparently, the spatial separation of denitrification and methanogenesis zones inside the UASB reactor allowed nitrite reduction and methanogenesis to occur at the same moment. Batch tests showed that granules seem to protect methanogens from nitrite inhibition, probably due to transport limitations. Combined COD and N removal via nitrite in a single-stage UASB reactor could be a feasible technology to treat high-strength domestic wastewater. PMID- 26676013 TI - Comparison of the treatment performance of hybrid constructed wetlands treating stormwater runoff. AB - This study was conducted to compare the treatment performance of two hybrid constructed wetlands (CWs) in treating stormwater runoff. The hybrid CWs were composed of a combination of free water surface (FWS) and horizontal subsurface flow (HSSF) CWs. Based on the results, strong correlation exists between potential runoff impacts and stormwater characteristics; however, the low correlations also suggest that not only the monitored parameters contribute to stormwater event mean concentrations (EMC) of pollutants, but other factors should also be considered as well. In the hydraulic and treatment performance of the hybrid CWs, a small surface area to catchment area (SA/CA) ratio, receiving a high concentration of influent EMC, will find it hard to achieve great removal efficiency; also a large SA/CA ratio, receiving low concentration of influent EMC, will find it hard to achieve great removal efficiency. With this, SA/CA ratio and influent characteristics such as EMC or load should be considered among the design factors of CWs. The performance data of the two CWs were used to consider the most cost-effective design of a hybrid CW. The optimum facility capacity (ratio of total runoff volume to storage volume) that is applicable for a target volume reduction and removal efficiency was provided in this study. PMID- 26676014 TI - Modelling and characterization of primary settlers in view of whole plant and resource recovery modelling. AB - Characterization and modelling of primary settlers have been neglected pretty much to date. However, whole plant and resource recovery modelling requires primary settler model development, as current models lack detail in describing the dynamics and the diversity of the removal process for different particulate fractions. This paper focuses on the improved modelling and experimental characterization of primary settlers. First, a new modelling concept based on particle settling velocity distribution is proposed which is then applied for the development of an improved primary settler model as well as for its characterization under addition of chemicals (chemically enhanced primary treatment, CEPT). This model is compared to two existing simple primary settler models (Otterpohl and Freund; Lessard and Beck), showing to be better than the first one and statistically comparable to the second one, but with easier calibration thanks to the ease with which wastewater characteristics can be translated into model parameters. Second, the changes in the activated sludge model (ASM)-based chemical oxygen demand fractionation between inlet and outlet induced by primary settling is investigated, showing that typical wastewater fractions are modified by primary treatment. As they clearly impact the downstream processes, both model improvements demonstrate the need for more detailed primary settler models in view of whole plant modelling. PMID- 26676015 TI - Comparison of linear and non-linear models for the adsorption of fluoride onto geo-material: limonite. AB - The three widely used isotherms Langmuir, Freundlich and Temkin were examined in an experiment using fluoride (F-) ion adsorption on a geo-material (limonite) at four different temperatures by linear and non-linear models. Comparison of linear and non-linear regression models were given in selecting the optimum isotherm for the experimental results. The coefficient of determination, r2, was used to select the best theoretical isotherm. The four Langmuir linear equations (1, 2, 3, and 4) are discussed. Langmuir isotherm parameters obtained from the four Langmuir linear equations using the linear model differed but they were the same when using the nonlinear model. Langmuir-2 isotherm is one of the linear forms, and it had the highest coefficient of determination (r2 = 0.99) compared to the other Langmuir linear equations (1, 3 and 4) in linear form, whereas, for non linear, Langmuir-4 fitted best among all the isotherms because it had the highest coefficient of determination (r2 = 0.99). The results showed that the non-linear model may be a better way to obtain the parameters. In the present work, the thermodynamic parameters show that the absorption of fluoride onto limonite is both spontaneous (DeltaG < 0) and endothermic (DeltaH > 0). Scanning electron microscope and X-ray diffraction images also confirm the adsorption of F- ion onto limonite. The isotherm and kinetic study reveals that limonite can be used as an adsorbent for fluoride removal. In future we can develop new technology for fluoride removal in large scale by using limonite which is cost-effective, eco friendly and is easily available in the study area. PMID- 26676016 TI - Hydrogel-swelling driven delivery device for corrosion resistance of metal in water. AB - Corrosion on steel and copper pipes in industry can trigger pollution and weakness due to undesired chemical and biochemical reactions. Too much or too little inhibitor can decrease its efficiency, even causing waste and pollution. In this contribution, an innovative delivery device driven by hydrogel swelling, mainly consisting of a semi-permeable membrane, a hydrogel-swelling force drive and a release orifice, was developed to control the release of inhibitor in a water system at a constant rate, leading the amount of inhibitor to maintain a proper concentration. The effects of hydrogel mass and orifice dimension on release property were studied for controlling release rate. Moreover, a weight loss experiment on carbon steels was carried out to show the incredible anti corrosion function of the system. PMID- 26676017 TI - Application of membrane processes in fractionation of elements in river water. AB - The influence of wastewater treatment plant (WWTP) effluents from one microelectronic industrial zone on element concentrations and partitioning in river water was investigated. The stepwise membrane filtration is used to distinguish different size fractions including large particulate (>18 MUm), particulate (0.2-18 MUm), colloidal/nanoparticle (10 kDa-0.2 MUm) and truly dissolved fractions (<10 kDa) in river water samples and WWTP effluents. Results demonstrated that anthropogenic inputs (WWTP effluents and industrial area) had an important influence on concentrations and partitioning of some elements in river water. Mass balance results showed that membrane filtration processes could realize a good fractionation for many elements (good recoveries) in water samples. Flux decline during 0.2 MUm and 10 kDa filtrations were analyzed, and corresponding fouling mechanisms are discussed. PMID- 26676018 TI - Recovery rate of multiple enteric viruses artificially seeded in water and concentrated by adsorption-elution with negatively charged membranes: interaction and interference between different virus species. AB - Viral concentration method by adsorption-elution with negative membranes has been widely employed for concentrating viruses from environmental samples. In order to provide an adequate assessment of its recovery efficiency, this study was conducted to assess viral recovery rates for viral species commonly found in water (HAdV-5, EV, RV, BAdV and CAV-2), quantifying viral genomes at the end of the five different steps of the process. Recovery rates were analyzed for several viruses combined in a single water sample and for each virus assayed separately. Ultrapure water samples were artificially contaminated and analyzed by real-time quantitative polymerase chain reaction (qPCR). High recovery rates were found after the final stage when assessed individually (89 to 125%) and combined in the same sample (23 to > 164%). HAdV-5 exhibited >100% recovery when assayed with human viruses and other AdVs, whereas BAdV and CAV-2 were not detected. These data suggest that recovery efficiency could be related to viral structural characteristics, their electric charges and other interactions, so that they are retained with greater or lesser efficiency when coupled. This protocol could be applied to environmental samples, since high recovery rates were observed and infectious viruses were detected at the end of the concentration process. PMID- 26676019 TI - Treatment of domestic wastewater with an anaerobic ceramic membrane bioreactor (AnCMBR). AB - In this study, a ceramic membrane with a pore size of 80 nm was incorporated into an anaerobic membrane bioreactor for excellent stability and integrity. Chemical oxygen demand (COD) removal efficiencies by biodegradation reached 78.6 +/- 6.0% with mixed liquor suspended solids (MLSS) of 12.8 +/- 1.2 g/L. Even though the total methane generated was 0.3 +/- 0.03 L/g CODutilized, around 67.4% of it dissolved in permeate and was lost beyond collection. As a result, dissolved methane was 2.7 times of the theoretical saturating concentration calculated from Henry's law. When transmembrane pressure (TMP) of the ceramic membrane reached 30 kPa after 25.3 d, 95.2% of the total resistance was attributed to the cake layer, which made it the major contributor to membrane fouling. Compared to the mixed liquor, cake layer was rich in colloids and soluble products that could bind the solids to form a dense cake layer. The Methanosarcinaceae family preferred to attach to the ceramic membranes. PMID- 26676020 TI - Pilot test of pollution control and metal resource recovery for acid mine drainage. AB - The study was undertaken in order to recover the metal resources from acid mine drainage (AMD). A 300 m(3)/d continuous system was designed and fractional precipitation technology employed for the main metals Fe, Cu, Zn, and Mn recovery. The system was operated for six months using actual AMD in situ. The chemicals' input and also the retention time was optimized. Furthermore, the material balance was investigated. With the system, the heavy metals of the effluent after the Mn neutralization precipitation were below the threshold value of the Chinese integrated wastewater discharge limit. The precipitates generated contained 42%, 12%, 31%, and 18% for Fe, Cu, Zn, and Mn, respectively, and the recovery rates of Fe, Cu, Zn, and Mn were 82%, 79%, 83%, and 83%, respectively. The yield range of the precipitate had significant correlation with the influent metal content. Using the X-ray diffraction analysis, the refinement for Fe, Cu, and Zn could be achieved through the processes of roasting and floatation. Cost benefit was also discussed; the benefit from the recycled metal was able to pay for the cost of chemical reagents used. Most important of all, through the use of this technology, the frustrating sludge problems were solved. PMID- 26676021 TI - Comprehensive understanding of nano-sized particle separation processes using nanoparticle tracking analysis. AB - The understanding of nano-sized particle separation processes has been limited by difficulties of nanoparticle characterization. In this study, nanoparticle tracking analysis (NTA) was deployed to evaluate the absolute particle size distributions in laboratory scale flocculation and filtration experiments with silver nanoparticles. The results from NTA were consistent with standard theories of particle destabilization and transport. Direct observations of changes in absolute particle size distributions from NTA enhance both qualitative and quantitative understanding of particle separation processes of nano-sized particles. PMID- 26676022 TI - Scaling and root planning, and locally delivered minocycline reduces the load of Prevotella intermedia in an interdependent pattern, correlating with symptomatic improvements of chronic periodontitis: a short-term randomized clinical trial. AB - BACKGROUND: To evaluate the respective or combinatory efficacy of locally delivered 2% minocycline (MO), and scaling and root planning (SRP) by assessing both clinical parameters and the loads of four main periodontal pathogens in treating chronic periodontitis (CP). METHODS: Seventy adults with CP were randomly assigned to the three treatment groups: 1) SRP alone; 2) MO alone; and 3) combinatory use of SRP and MO (SRP + MO). Before and 7 days after the treatments, we evaluated both clinical parameters (pocket depth [PD] and sulcus bleeding index [SBI]) and the gene load of four main periodontal pathogens (Aggregatibacter actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Porphyromonas gingivalis [Pg], and Prevotella intermedia [Pi]). RESULTS: The bacterial prevalence per patient was: Aa, 31.25%; Fn, 100%; Pg, 95.31%; and Pi, 98.44%. Seven days after treatment, the three treatments significantly reduced both PD and SBI, but not detection frequencies of the four pathogens. For PD, the reduction efficacy of SRP + MO was significantly higher than that of either MO or SRP. Only Pg responded significantly to SRP. Pg and Fn were significantly reduced in the presence of MO. Only SRP + MO showed a significant reduction effect on the gene load of Pi. The reduction of PD significantly correlated with the gene load of Pi (r=0.26; P=0.042) but not of the other bacteria. CONCLUSION: SRP and MO reduced the load of Pi in an interdependent pattern, which correlated with symptomatic improvements of CP. PMID- 26676023 TI - Hypertension Prevalence, Awareness and Control Levels among Ghawarna: An African Descendant Ethnic Minority in the Jordan Valley. AB - OBJECTIVE: Treatment and control of hypertension (HTN) is a challenging issue as undiagnosed HTN prevalence seems to be high among certain ethnic groups, such as African-descendant populations. The current study attempted to measure HTN prevalence, awareness and control levels among Ghawarna, an African-descendant ethnic group living in the Jordan Valley (Al-Ghawr). DESIGN SETTING AND PARTICIPANTS: A cross-sectional study was conducted in a community of Ghawarna between March and June 2013 in Ghawr Al-Mazraa Village in the southern part of the Jordan Valley. A total of 517 participants, aged >25 years, were randomly selected using cluster random sampling technique. MAIN MEASURES: Data were collected using an interviewer-administrated questionnaire and on-location measurement of blood pressure (BP), height, and weight. Prevalence rates were compared by sex and age groups using chi-square test while backward selection logistic regression analysis was used to identify predictors of HTN. RESULTS: We found 229 (44.3%) of the 517 participants had HTN. Of those 229 hypertensives, 146 (28.2%) participants were discovered to have HTN for the "first time." Only 23 of the 83 who were aware of their hypertension had their BP controlled. When we added the undiagnosed HTN (n=146) to the uncontrolled HTN (n=60), the prevalence of uncontrolled HTN became 90% (206/229). Older age, higher BMI, diabetes mellitus, and dyslipidemia were associated with having HTN. CONCLUSIONS: HTN prevalence, awareness and control levels are alarming among Ghawarna. PMID- 26676024 TI - Vallabhaneni Sita Rama Das, 1933-2010: teacher and mentor. AB - We present here the life and research of V. S. Rama Das, a distinguished Indian botanist who specialized in photosynthesis. He was the first to purify chloroplasts that were free of mitochondrial contamination. He then studied C4, C3-C4 intermediate and CAM pathways, as well as their taxonomic distribution in tropical climates. His most valuable legacy is that he, as a philosopher, inspired and guided many students to pursue their research career in India. Also see Narayana and Pullaiah (Eminent Indian Botanists: Past and present: Biographies and contributions, pp 394-401, 2010) and Raghavendra and Reddy (Curr Sci 101:798-799, 2011) for further information on Rama Das. PMID- 26676025 TI - Efficiency Enhancement of Silicon Heterojunction Solar Cells via Photon Management Using Graphene Quantum Dot as Downconverters. AB - By employing graphene quantum dots (GQDs), we have achieved a high efficiency of 16.55% in n-type Si heterojunction solar cells. The efficiency enhancement is based on the photon downconversion phenomenon of GQDs to make more photons absorbed in the depletion region for effective carrier separation, leading to the enhanced photovoltaic effect. The short circuit current and the fill factor are increased from 35.31 to 37.47 mA/cm(2) and 70.29% to 72.51%, respectively. The work demonstrated here holds the promise for incorporating graphene-based materials in commercially available solar devices for developing ultrahigh efficiency photovoltaic cells in the future. PMID- 26676026 TI - Dissuasive cigarette sticks: the next step in standardised ('plain') packaging? AB - BACKGROUND: Standardised (or 'plain') packaging has reduced the appeal of smoking by removing imagery that smokers use to affiliate themselves with the brand they smoke. We examined whether changing the appearance of cigarette sticks could further denormalise smoking and enhance the negative impact of standardised packaging. METHODS: We conducted an online study of 313 New Zealand smokers who comprised a Best-Worst Choice experiment and a rating task. The Best-Worst experiment used a 2*3*3*6 orthogonal design to test the following attributes: on pack warning message, branding level, warning size and stick appearance. RESULTS: We identified three segments whose members' choice patterns were strongly influenced by the stick design, warning theme and size, and warning theme, respectively. Each of the dissuasive sticks tested was less preferred and rated as less appealing than the most common stick in use; a 'minutes of life lost' stick was the most aversive of the stimuli tested. CONCLUSIONS: Dissuasive sticks could enhance the effect of standardised packaging, particularly among older smokers who are often more heavily addicted and resistant to change. Countries introducing standardised packaging legislation should take the opportunity to denormalise the appearance of cigarette sticks, in addition to removing external tobacco branding from packs and increasing the warning size. PMID- 26676027 TI - Austin Powers bites back: a cross sectional comparison of US and English national oral health surveys. AB - OBJECTIVE: To compare oral health in the US and England and to assess levels of educational and income related oral health inequalities between both countries. DESIGN: Cross sectional analysis of US and English national surveys. SETTING: Non institutionalised adults living in their own homes. PARTICIPANTS: Oral health measures and socioeconomic indicators were assessed in nationally representative samples: the Adult Dental Health Survey 2009 for England, and the US National Health and Nutrition Examination Survey 2005-08. Adults aged >=25 years were included in analyses with samples of 8719 (England) and 9786 (US) for analyses by education, and 7184 (England) and 9094 (US) for analyses by income. MAIN OUTCOME MEASURES: Number of missing teeth, self rated oral health, and oral impacts on daily life were outcomes. Educational attainment and household income were used as socioeconomic indicators. Age standardised estimates of oral health were compared between countries and across educational and income groups. Regression models were fitted, and relative and absolute inequalities were measured using the relative index of inequality (RII) and the slope index of inequality (SII). RESULTS: The mean number of missing teeth was significantly higher in the US (7.31 (standard error 0.15)) than in England (6.97 (0.09)), while oral impacts were higher in England. There was evidence of significant social gradients in oral health in both countries, although differences in oral health by socioeconomic position varied according to the oral health measure used. Consistently higher RII and SII values were found in the US than in England, particularly for self rated oral health. RII estimates for self rated oral health by education were 3.67 (95% confidence interval 3.23 to 4.17) in the US and 1.83 (1.59 to 2.11) in England. In turn, SII values were 42.55 (38.14 to 46.96) in the US and 18.43 (14.01 to 22.85) in England. CONCLUSIONS: The oral health of US citizens is not better than the English, and there are consistently wider educational and income oral health inequalities in the US compared with England. PMID- 26676028 TI - Risk stratification for large artery or chronic coronary artery disease-related ischemic stroke in octogenarians undergoing exercise stress myocardial perfusion imaging: A cohort study. AB - OBJECTIVES: To test, if in octogenarians, treadmill exercise with myocardial perfusion imaging (exercise-MPI) can risk stratify for large artery or chronic CAD-related ischemic stroke (LACCIS). METHODS: Exercise-MPI-related data of 237 octogenarians (55% prior MI or revascularization) without previous stroke were registered and prospective follow-up was performed to document LACCIS. LACCIS was defined as acute onset of neurological symptoms with CT/MRI findings of non lacunar-type infarcts in the absence of atrial fibrillation or intracardiac embolic sources. RESULTS: After 7.3 years, 10 LACCIS were documented. SSS [HR 1.08 (1.02-1.13 95% CIs), SDS [HR 1.1 (1.04-1.16 95% CIs)], and non-sustained VT or transient AV block during exercise [HR 3.9 (1.7-9.0 95% CIs)] were predictors of LACCIS (P < .01 for all). A SSS threshold of 16 had 81% specificity for identification of future LACCIS and risk groups formed according to this cut-off had significantly different LACCIS-free survival (P = .015). CONCLUSION: Exercise MPI in octogenarians can provide risk stratification markers for LACCIS. PMID- 26676029 TI - Cardiac fibroma with high 18F-FDG uptake mimicking malignant tumor. PMID- 26676030 TI - Impact of respiratory motion correction on SPECT myocardial perfusion imaging using a mechanically moving phantom assembly with variable cardiac defects. AB - BACKGROUND: The aim of this study was to determine the impact of respiratory motion correction on SPECT MPI and on defect detection using a phantom assembly. METHODS: SPECT/CT data were acquired using an anthropomorphic phantom with inflatable lungs and with an ECG beating and moving cardiac compartment. The heart motion followed the respiratory pattern in the cranio-caudal direction to simulate normal or deep breathing. Small or large transmural defects were inserted into the myocardial wall of the left ventricle. SPECT/CT images were acquired for each of the four respiratory phases, from exhale to inhale. A respiratory motion correction was applied using an image-based method with transformation parameters derived from the SPECT data by a non-rigid registration algorithm. A report on defect detection from two physicians and a quantitative analysis on MPI data were performed before and after applying motion correction. RESULTS: Respiratory motion correction eliminated artifacts present in the images, resulting in a uniform uptake and reduction of motion blurring, especially in the inferior and anterior regions of the LV myocardial walls. The physicians' report after motion correction showed that images were corrected for motion. CONCLUSIONS: A combination of motion correction with attenuation correction reduces artifacts in SPECT MPI. AC-SPECT images with and without motion correction should be simultaneously inspected to report on small defects. PMID- 26676031 TI - Some Review Journals Do Not Allow Students to Author Reviews: Is this Ethical? PMID- 26676032 TI - The Central Importance of Laboratories for Reducing Waste in Biomedical Research. AB - The global biomedical research enterprise is driving substantial advances in medicine and healthcare. Yet it appears that the enterprise is rather wasteful, falling short of its true innovative potential. Suggested reasons are manifold and involve various stakeholders, such that there is no single remedy. In the present paper, I will argue that laboratories are the basic working units of the biomedical research enterprise and an important site of action for corrective intervention. Keeping laboratories relatively small will enable better training and mentoring of individual scientists, which in turn will yield better performance of the scientific workforce. The key premise of this argument is that people are at the heart of the successes and failures of biomedical research, yet the human dimension of science has been unduly neglected in practice. Renewed focus on the importance of laboratories and their constituent scientists is one promising approach to reducing waste and increasing efficiency within the biomedical research enterprise. PMID- 26676033 TI - Animal Models Used to Study Superantigen-Mediated Diseases. AB - Superantigens secreted by Staphylococcus aureus and Streptococcus pyogenes interact with the T-cell receptor and major histocompatibility class II molecules on antigen-presenting cells to elicit a massive cytokine release and activation of T cells in higher numbers than that seen with ordinary antigens. Because of this unique ability, superantigens have been implicated as etiological agents for many different types of diseases, including toxic shock syndrome, infective endocarditis, pneumonia, and inflammatory skin diseases. This review covers the main animal models that have been developed in order to identify the roles of superantigens in human disease. PMID- 26676034 TI - Identification, Purification, and Characterization of Staphylococcal Superantigens. AB - Purifying natively produced staphylococcal superantigens is an important process in the study of these proteins, as many common methods of protein purification are affected by staphylococcal protein A contamination. Here, we describe a proven approach for identifying superantigens in vitro as well as for purifying novel superantigens both in His-tagged and native forms using modern genetic tools coupled with thin-layer isoelectric focusing. PMID- 26676035 TI - Strain Discrimination of Staphylococcus aureus Using Superantigen Profiles. AB - Staphylococcus aureus is one of the major bacterial species that may cause clinical infection and food-poisoning cases. Strains of this species may produce a series of superantigens (SAgs). Due to the importance of staphylococcal infections, reliable methods for the discrimination of strains of this species are important. Such data may allow us to trace the infection origins and be used for epidemiological study. For strain discrimination, genotyping methods, such as pulsed-field gel electrophoresis (PFGE), random amplified polymorphic DNA (RAPD), and multi-locus sequence typing (MLST), etc., could be used. Recently, toxin gene profiles, which can be used for the elucidation of the genetic and pathogenic relatedness between strains, also have been used to improve the strain discrimination. For S. aureus, as more SAg genes were discovered, the SAg profiles become more useful for the strain discrimination of S. aureus. In this chapter, a method for the discrimination of S. aureus strains using superantigen profiles will be described in detail. PMID- 26676036 TI - Crystallization and Structure Determination of Superantigens and Immune Receptor Complexes. AB - Structure determination of superantigens and the complexes they form with immune receptors have over the years provided insight in their modes of action. This technique requires growing large and highly ordered crystals of the superantigen or receptor-superantigen complex, followed by exposure to X-ray radiation and data collection. Here, we describe methods for crystallizing superantigens and superantigen-receptor complexes using the vapor diffusion technique, how the crystals may be optimized, and lastly data collection and structure determination. PMID- 26676037 TI - Lipopolysaccharide-Induced Toxic Shock Syndrome in Rabbits. AB - Enhancement of susceptibility to lipopolysaccharide (LPS; endotoxin) is a defining characteristic of Staphylococcus aureus superantigens. At the time of this publication, there are 24 identified staphylococcal superantigens (SAgs), some of which have yet to be fully characterized. Testing the capacity of superantigens to potentiate LPS sensitivity is essential to characterize the role of these proteins in disease development. Here we describe how to perform studies of the enhancement of LPS-induced toxic shock syndrome in rabbits. This protocol also provides information on a second important activity of superantigens: the production of fever. PMID- 26676038 TI - Aortic Valve Damage for the Study of Left-Sided, Native Valve Infective Endocarditis in Rabbits. AB - Infective endocarditis affects approximately 100,000 individuals in the USA. Medical advances have contributed to the rise of the disease, and no new therapies have emerged in the last 50 years to control the surge of this life threatening infection. The rabbit vascular physiology and immune response mechanisms are similar to humans. Hence, the rabbit model of infective endocarditis is an excellent research tool with which to address many questions regarding development of endocarditis, for the testing of new therapies, and for the study of the molecular mechanisms used by infectious agents to cause disease. This chapter describes the surgical procedure required to study infective endocarditis in damaged native valves, therefore closely mimicking human disease. PMID- 26676039 TI - Rabbit Model for Superantigen-Mediated Lethal Pulmonary Disease. AB - Staphylococcus aureus is a highly significant cause of serious human infections in the USA. Many of these illnesses are mediated by interactions between the host immune system and staphylococcal superantigens (SAgs). Several of these severe staphylococcal infections are initiated in the lungs, making this an important site to study. Here, we describe the rabbit model for investigating the role of staphylococcal SAgs in pulmonary-associated lethal infection and intoxication. PMID- 26676040 TI - Nasopharyngeal Infection of Mice with Streptococcus pyogenes and In Vivo Detection of Superantigen Activity. AB - Streptococcus pyogenes is a globally prominent human-specific pathogen that is responsible for an enormous burden of infectious disease. Despite intensive experimental efforts to understand the molecular correlates that contribute to invasive infections, there has been less focus on S. pyogenes carriage and local infection of the nasopharynx. This chapter describes an acute nasopharyngeal infection model in mice that is utilized in our laboratory to study the role of superantigen toxins in the biology of S. pyogenes. We also describe a method to detect superantigen-specific T cell activation in vivo. PMID- 26676041 TI - Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice. AB - Staphylococcus aureus can exist as a colonizer or can cause a spectrum of diseases. S. aureus elaborates several exotoxins and the superantigens are one among them. Staphylococcal superantigens (SSAg) cause robust activation of the immune system and acute exposure to significant amounts of SSAg can be potentially lethal. However, chronic exposure to SSAg is also possible. Administering SSAg using mini-osmotic pumps may mimic chronic recurrent exposure to SSAg. This is a relatively simple and safe way to administer purified SSAg or any other toxin/agent. In this chapter, we describe the mini-osmotic pump mediated delivery of SSAg. PMID- 26676042 TI - A Sublethal Swine Model for Defining In Vivo Superantigen-Induced Responses Following Exposure to Staphylococcal Enterotoxin B. AB - In vivo responses to bacterially derived superantigen-like toxins have been difficult to define due to the inherent limitations with rodent models and the relevance that the results obtained from such models may, or may not, have for human pathophysiology. Further the use of challenge doses of superantigen toxins that are lethal or supra-lethal complicates analogies to human exposures which are rarely fatal. Here, we utilize the superantigen, staphylococcal enterotoxin B, at doses that are sublethal in a swine model of toxin-induced incapacitation. Relevant dosing using an animal species for which this toxin is a true superantigen distinguishes this model. PMID- 26676043 TI - Monkey Feeding Assay for Testing Emetic Activity of Staphylococcal Enterotoxin. AB - Staphylococcal enterotoxins (SEs) are unique bacterial toxins that cause gastrointestinal toxicity as well as superantigenic activity. Since systemic administration of SEs induces superantigenic activity leading to toxic shock syndrome that may mimic enterotoxic activity of SEs such as vomiting and diarrhea, oral administration of SEs in the monkey feeding assay is considered as a standard method to evaluate emetic activity of SEs. This chapter summarizes and discusses practical considerations of the monkey feeding assay used in studies characterizing classical and newly identified SEs. PMID- 26676044 TI - Use of an Ex Vivo Porcine Mucosal Model to Study Superantigen Penetration. AB - In vitro perfusion studies are frequently used to determine the penetration of compounds through skin and mucosa. Porcine tissue has been shown to be an excellent model for human tissue in terms of structure, function, and reactivity. We describe the use of porcine tissue ex-vivo in a continuous flow perfusion system to study the behavior of superantigens in this model. PMID- 26676045 TI - Protocol for Examining Human Vaginal Epithelial Cell Signaling in Response to Staphylococcal Superantigens. AB - A detailed investigation of eukaryotic signaling pathways affected by bacterial products is key to our understanding of host-pathogen interactions. Cytokine expression appears to be an important initial host cell response to many bacterial products, including the Staphylococcus aureus superantigens (SAgs). While much is understood about how SAgs signal to immune cells, very little is known about the specific cellular pathways activated by SAgs on nonimmune cells such as those of the epithelium. Here, we describe methods for analyzing SAg signaling in cultured epithelial cells, which may be extrapolated to the analysis of signaling pathways induced by other bacterial ligands on a variety of cell types. PMID- 26676046 TI - Organ Culture as a Model System for Studies on Enterotoxin Interactions with the Intestinal Epithelium. AB - Studies on bacterial enterotoxin-epithelium interactions require model systems capable of mimicking the events occurring at the molecular and cellular levels during intoxication. In this chapter, we describe organ culture as an often neglected alternative to whole-animal experiments or enterocyte-like cell lines. Like cell culture, organ culture is versatile and suitable for studying rapidly occurring events, such as enterotoxin binding and uptake. In addition, it is advantageous in offering an epithelium with more authentic permeability/barrier properties than any cell line, as well as a subepithelial lamina propria, harboring the immune cells of the gut mucosa. PMID- 26676047 TI - Quantification of a Selective Expansion of T Cell Receptor Vbeta by Superantigen Using Real-Time PCR. AB - Selective expansion of T cells bearing specific T cell receptor Vbeta segments is a hallmark of superantigens. Analyzing Vbeta specificity of superantigens is important for characterizing newly discovered superantigens and understanding differential T cell responses to each toxin. Here, we describe a real-time PCR method using SYBR green I and primers specific to Cbeta and Vbeta genes for an absolute quantification. The established method was applied to quantify a selective expansion of T cell receptor Vbeta expansion by superantigens and generated accurate, reproducible, and comparable results. PMID- 26676048 TI - Induction of Human Regulatory T Cells with Bacterial Superantigens. AB - Regulatory T cells (Tregs) that suppress the activation of immune effector cells limit immunopathology and are fast emerging as therapeutic targets for autoimmune and cancer disease. Tools enabling Treg in vitro-induction, expansion, and characterization and manipulation will help future clinical developments. In this chapter, we describe in detail how to use bacterial superantigens to induce human Tregs efficiently from peripheral blood mononuclear cells. How to assess human Treg phenotype and suppressive capacity are also described. Technical details, variations, and alternative experimental conditions are provided. PMID- 26676049 TI - Construction of Recombinant Single Chain Variable Fragment (ScFv) Antibody Against Superantigen for Immunodetection Using Antibody Phage Display Technology. AB - Superantigens are a class of antigens that bind to the major histocompatibility complex class (MHC) II and T-cell receptor (TCR) and cause the nonspecific activation of T cells, resulting in a massive release of pro-inflammatory mediators. They are produced by the gram-positive organisms Staphylococcus aureus and Streptococcus pyogenes, and by a variety of other microbes such as viruses and mycoplasma, and cause toxic shock syndrome (TSS) and even death in some cases. The immunodetection of superantigens is difficult due to the polyclonal activation of T-cells leading to nonspecific antibody production. The production of recombinant monoclonal antibodies against superantigens can solve this problem and are far better than polyclonal antibodies in terms of detection. Here, we describe the construction of recombinant single chain variable fragments (ScFv) antibodies against superantigens with specific reference to SEB (staphylococcal enterotoxin B) using antibody phage display technology. PMID- 26676050 TI - Contraceptive Provision to Adolescent Females Prescribed Teratogenic Medications. AB - BACKGROUND AND OBJECTIVES: Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population. METHODS: A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic medical records were queried for demographic information, evidence of contraceptive provision, and menstrual and sexual histories. The data were analyzed using standard statistical methods. RESULTS: Within 4172 clinic visits, 1694 females received 4506 prescriptions for teratogenic medications. The most commonly prescribed teratogens were topiramate, methotrexate, diazepam, isotretinoin, and enalapril. The subspecialties prescribing teratogens most frequently were neurology, hematology-oncology, and dermatology. Overall, contraceptive provision was documented in 28.6% of the visits. Whites versus nonwhites and older versus younger girls were more likely to receive contraceptive provision. The presence of a federal risk mitigation system for the teratogen also increased the likelihood of contraceptive provision. CONCLUSIONS: Our data demonstrate female adolescents prescribed teratogens receive inadequate contraception provision, which could increase their risk for negative pregnancy outcomes. Although the presence of a federal risk mitigation system appears to improve contraceptive provision, these systems are costly and, in some instances, difficult to implement. Efforts to improve provider practices are needed. PMID- 26676051 TI - All Adolescents Deserve Routine Conversations About Sexual Activity and Pregnancy Prevention. PMID- 26676052 TI - Proanorexia Communities on Social Media. PMID- 26676053 TI - Myosin content of individual human muscle fibers isolated by laser capture microdissection. AB - Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as alpha-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. PMID- 26676054 TI - Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling. AB - BACKGROUND: Postmenopausal osteoporosis is a common bone disease and characterized by low bone mineral density. AIM: This study aimed to reveal key genes associated with postmenopausal osteoporosis (PMO), and provide a theoretical basis for subsequent experiments. METHODS: The dataset GSE7429 was obtained from Gene Expression Omnibus. A total of 20 B cell samples (ten ones, respectively from postmenopausal women with low or high bone mineral density (BMD) were included in this dataset. Following screening of differentially expressed genes (DEGs), coexpression analysis of all genes was performed, and key genes in the coexpression network were screened using the random walk algorithm. Afterwards, functional and pathway analyses were conducted. Additionally, protein protein interactions (PPIs) between DEGs and key genes were analyzed. RESULTS: A set of 308 DEGs (170 up-regulated ones and 138 down-regulated ones) between low BMD and high BMD samples were identified, and 101 key genes in the coexpression network were screened out. In the coexpression network, some genes had a higher score and degree, such as CSTA. The key genes in the coexpression network were mainly enriched in GO terms of the defense response (e.g., SERPINA1 and CST3), immune response (e.g., IL32 and CLEC7A); while, the DEGs were mainly enriched in structural constituent of cytoskeleton (e.g., CYLC2 and TUBA1B) and membrane enclosed lumen (e.g., CCNE1 and INTS5). In the PPI network, CCNE1 interacted with REL; and TUBA1B interacted with ESR1. CONCLUSIONS: A series of interactions, such as CSTA/TYROBP, CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of PMO. PMID- 26676055 TI - The long-term effect of uranium and pH on the community composition of an artificial consortium. AB - In the environment, microorganisms are living in diverse communities, which are impacted by the prevailing environmental conditions. Here, we present a study investigating the effect of low pH and elevated uranium concentration on the dynamics of an artificial microbial consortium. The members (Caulobacter sp. OR37, Asinibacterium sp. OR53, Ralstonia sp. OR214 and Rhodanobacter sp. OR444) were isolated from a uranium contaminated and acidic subsurface sediment. In pure culture, Ralstonia sp. OR214 had the highest growth rate at neutral and low pH and only Caulobacter sp. OR37 and Asinibacterium sp. OR53 grew in the presence uranium. The four strains were mixed in equal ratios, incubated at neutral and low pH and in the presence uranium and transferred to fresh medium once per week for 30 weeks. After 30 weeks, Ralstonia sp. OR214 was dominant at low and neutral pH and Caulobacter sp. OR37 and Asinibacterium sp. OR53 were dominant in the presence of uranium. After 12 weeks, the cultures were also transferred to new conditions to access the response of the consortia to changing conditions. The transfers showed an irreversible effect of uranium, but not of low pH on the consortia. Overall, the strains initially tolerant to the respective conditions persisted over time in high abundances in the consortia. PMID- 26676056 TI - Effects and mode of action of chitosan and ivy fruit saponins on the microbiome, fermentation and methanogenesis in the rumen simulation technique. AB - This study investigates the effects of supplementing a control diet (CON) with chitosan (CHI) or ivy fruit saponins (IVY) as natural feed additives. Both additives had similar abilities to decrease rumen methanogenesis (-42% and -40%, respectively) using different mechanisms: due to its antimicrobial and nutritional properties CHI promoted a shift in the fermentation pattern towards propionate production which explained about two thirds of the decrease in methanogenesis. This shift was achieved by a simplification of the structure in the bacterial community and a substitution of fibrolytic (Firmicutes and Fibrobacteres) by amylolytic bacteria (Bacteroidetes and Proteobacteria) which led to greater amylase activity, lactate and microbial protein yield with no detrimental effect on feed digestibility. Contrarily, IVY had negligible nutritional properties promoting minor changes in the fermentation pattern and on the bacterial community. Instead, IVY modified the structure of the methanogen community and decreased its diversity. This specific antimicrobial effect of IVY against methanogens was considered its main antimethanogenic mechanism. IVY had however a negative impact on microbial protein synthesis. Therefore, CHI and IVY should be further investigated in vivo to determine the optimum doses which maintain low methanogenesis but prevent negative effects on the rumen fermentation and animal metabolism. PMID- 26676057 TI - Elevated pCO2 causes a shift towards more toxic microcystin variants in nitrogen limited Microcystis aeruginosa. AB - Elevated pCO2 may promote phytoplankton growth, and potentially alleviate carbon limitation during dense blooms. Under nitrogen-limited conditions, elevated pCO2 may furthermore alter the phytoplankton carbon-nitrogen (C:N) balance and thereby the synthesis of secondary metabolites, such as cyanobacterial toxins. A common group of these toxins are the microcystins, with variants that differ not only in C:N stoichiometry, but also in toxicity. Here, we hypothesized that elevated pCO2 will increase the cellular C:N ratios of cyanobacteria, thereby promoting the more toxic microcystin variants with higher C:N ratios. To test this hypothesis, we performed chemostat experiments under nitrogen-limited conditions, exposing three Microcystis aeruginosa strains to two pCO2 treatments: 400 and 1200 MUatm. Biomass, cellular C:N ratios and total microcystin contents at steady state remained largely unaltered in all three strains. Across strains and treatments, however, cellular microcystin content decreased with increasing cellular C:N ratios, suggesting a general stoichiometric regulation. Furthermore, as predicted, microcystin variants with higher C:N ratios generally increased with elevated pCO2, while the variant with a low C:N ratio decreased. Thus, elevated pCO2 under nitrogen-limited conditions may shift the cellular microcystin composition towards the more toxic variants. Such CO2-driven changes may have consequences for the toxicity of Microcystis blooms. PMID- 26676058 TI - Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks. AB - Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable. PMID- 26676059 TI - Exercise training reduces the acute physiological severity of post-menopausal hot flushes. AB - KEY POINTS: A post-menopausal hot flush consists of profuse physiological elevations in cutaneous vasodilatation and sweating that are accompanied by reduced brain blood flow. These responses can be used to objectively quantify hot flush severity. The impact of an exercise training intervention on the physiological responses occurring during a hot flush is currently unknown. In a preference-controlled trial involving 21 post-menopausal women, 16 weeks of supervised moderate intensity exercise training was found to improve cardiorespiratory fitness and attenuate cutaneous vasodilatation, sweating and the reductions in cerebral blood flow during a hot flush. It is concluded that the improvements in fitness that are mediated by 16 weeks of exercise training reduce the severity of physiological symptoms that occur during a post-menopausal hot flush. A hot flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilatation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilatation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot flushes at baseline and follow-up. Fourteen participants opted for a 16 week moderate intensity supervised exercise intervention, while seven participants opted for control. Sweat rate, cutaneous vasodilatation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot flush sweat rate decreased by 0.04 mg cm(2) min(-1) at the chest (95% confidence interval 0.02 0.06, P = 0.01) and by 0.03 mg cm(2) min(-1) (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilatation by 9% (6-12%) at the chest and by 7% (4 9%) at forearm (P <= 0.05). Training attenuated hot flush MCAv by 3.4 cm s(-1) (0.7-5.1 cm s(-1) , P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot flushes by 109 arbitrary units (80-121, P < 0.001). These data indicate that exercise training leads to parallel reductions in hot flush severity and within-flush changes in cutaneous vasodilatation, sweating and cerebral blood flow. PMID- 26676060 TI - The Applications of Genetic Algorithms in Medicine. AB - A great wealth of information is hidden amid medical research data that in some cases cannot be easily analyzed, if at all, using classical statistical methods. Inspired by nature, metaheuristic algorithms have been developed to offer optimal or near-optimal solutions to complex data analysis and decision-making tasks in a reasonable time. Due to their powerful features, metaheuristic algorithms have frequently been used in other fields of sciences. In medicine, however, the use of these algorithms are not known by physicians who may well benefit by applying them to solve complex medical problems. Therefore, in this paper, we introduce the genetic algorithm and its applications in medicine. The use of the genetic algorithm has promising implications in various medical specialties including radiology, radiotherapy, oncology, pediatrics, cardiology, endocrinology, surgery, obstetrics and gynecology, pulmonology, infectious diseases, orthopedics, rehabilitation medicine, neurology, pharmacotherapy, and health care management. This review introduces the applications of the genetic algorithm in disease screening, diagnosis, treatment planning, pharmacovigilance, prognosis, and health care management, and enables physicians to envision possible applications of this metaheuristic method in their medical career.]. PMID- 26676061 TI - CROSS-CULTURAL ADAPTATION AND VALIDATION OF THE KOREAN VERSION OF THE CUMBERLAND ANKLE INSTABILITY TOOL. AB - BACKGROUND: The Cumberland Ankle Instability Tool (CAIT) is a valid and reliable patient reported outcome used to assess the presence and severity of chronic ankle instability (CAI). The CAIT has been cross-culturally adapted into other languages for use in non-English speaking populations. However, there are no valid questionnaires to assess CAI in individuals who speak Korean. PURPOSE: The purpose of this study was to translate, cross-culturally adapt, and validate the CAIT, for use in a Korean-speaking population with CAI. STUDY DESIGN: Cross cultural reliability study. METHODS: The CAIT was cross-culturally adapted into Korean according to accepted guidelines and renamed the Cumberland Ankle Instability Tool-Korean (CAIT-K). Twenty-three participants (12 males, 11 females) who were bilingual in English and Korean were recruited and completed the original and adapted versions to assess agreement between versions. An additional 168 national level Korean athletes (106 male, 62 females; age = 20.3 +/- 1.1 yrs), who participated in >= 90 minutes of physical activity per week, completed the final version of the CAIT-K twice within 14 days. Their completed questionnaires were assessed for internal consistency, test-retest reliability, criterion validity, and construct validity. RESULTS: For bilingual participants, intra-class correlation coefficients (ICC2,1) between the CAIT and the CAIT-K for test-retest reliability were 0.95 (SEM=1.83) and 0.96 (SEM=1.50) in right and left limbs, respectively. The Cronbach's alpha coefficients were 0.92 and 0.90 for the CAIT-K in right and left limbs, respectively. For native Korean speakers, the CAIT-K had high internal consistency (Cronbach's alpha=0.89) and intra-class correlation coefficient (ICC2,1 = 0.94, SEM=1.72), correlation with the physical component score (rho=0.70, p = 0.001) of the Short-Form Health Survey (SF-36), and the Kaiser-Meyer-Olkin score was 0.87. CONCLUSIONS: The original CAIT was translated, cross-culturally adapted, and validated from English to Korean. The CAIT-K appears to be valid and reliable and could be useful in assessing the Korean speaking population with CAI. PMID- 26676062 TI - Ultrasound quiz. PMID- 26676063 TI - Spontaneous Pneumoperitoneum due to Constipation. AB - We report a rare case of spontaneous pneumoperitoneum. An 82-year-old Japanese male patient was referred to our hospital because of constipation and abdominal pain. Abdominal computed tomography revealed a large amount of feces in the colon and rectum, and free air in the abdomen. Based on these findings, the patient was diagnosed with gastrointestinal perforation. Emergency exploratory laparotomy was performed. Neither perforation nor ischemic changes were recognized in the digestive tract. The patient's defecation was managed postoperatively until discharge on the 13th postoperative day. The authors assumed that free air, which was released after a mucosal injury due to the internal pressure caused by the presence of a large amount of feces in the colon and rectum, had penetrated the bowel wall through the bowel mucosa. We herein report the present case while also reviewing the pertinent literature. PMID- 26676064 TI - Calcitriol/calcifediol ratio: An indicator of vitamin D hydroxylation efficiency? AB - BACKGROUND: Calcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency. METHODS: We evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2-5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20). RESULTS: The geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or >=20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating. CONCLUSION AND GENERAL SIGNIFICANCE: In conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations. PMID- 26676065 TI - Shigellosis in refugees, Austria, July to November 2015. AB - We report on a cluster of shigellosis including 21 cases in refugees and two in local residents who worked in refugee transit centres, detected in Austria in 2015, between calendar weeks 29 and 47. The species isolated from the cluster cases, including one mixed infection, were S. sonnei (n = 13), S. flexneri (n = 10) and S. boydii (n = 1). Eleven of 18 tested isolates were extended spectrum beta-lactamase (ESBL)-positive, including five of six ciprofloxacin-resistant and three azithromycin-resistant isolates. PMID- 26676066 TI - Homonuclear Mixed-Valent Cobalt Imidazolate Framework for Oxygen-Evolution Electrocatalysis. AB - Herein, the synthesis and characterization of the first mixed-valent, purely cobalt-based zeolitic imidazolate framework, Co(II)3Co(III)2(C3H3N2)12 is presented. The material adopts the cubic garnet-type structure and combines high thermal stability of up to 350 degrees C with excellent chemical stability. Electrochemical characterization showed that the cobalt centres are redox active and efficiently support oxygen evolution, thus rendering this framework a potential candidate for single-site heterogeneous catalysis based on earth abundant elements. PMID- 26676068 TI - Editorial review: pediatric 3D ultrasound. AB - Three-dimensional ultrasound is an established diagnostic imaging technique in many specialties. However, in neonates, infants and children three-dimensional ultrasound still is underutilized, partially due to time constraints for post processing and restricted availability, of devices as well as dedicated pediatric transducers. Also reimbursement issues still need to be addressed. This editorial review presents more or less established pediatric three-dimensional ultrasound applications with proven diagnostic benefit as well as potential future applications of three-dimensional/four-dimensional ultrasound in infants and children, aiming at enhancing research and promoting practical use of three dimensional ultrasound in relevant pediatric conditions. Particularly, applications in neonatal neurosonography, ultrasound of the urogenital tract as well as some other small part and miscellaneous queries are highlighted. Additional other potential and future indications are discussed briefly, also mentioning restrictions and potential future developments. In summary, three dimensional ultrasound holds some potential to widen sonographic diagnostic capabilities throughout childhood and hopefully will be increasingly investigated and introduced into clinical practice provided respective equipment and pediatric three-dimensional/four-dimensional ultrasound transducers become available. PMID- 26676067 TI - Loss of muscle mass: current developments in cachexia and sarcopenia focused on biomarkers and treatment. AB - Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies, and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartate-resistant acid phosphatase 5a, and novel substances like epigallocatechin-3-gallate. In summary, the progress to combat muscle wasting is in full swing, and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon support by improved and more helpful strategies. PMID- 26676069 TI - Autoantibody Profile of Adult Patients With Childhood Onset Type 2 Autoimmune Hepatitis. AB - BACKGROUND: Anti-liver kidney microsome (anti-LKM) autoantibodies are a distinguishing feature of type II autoimmune hepatitis (AIH-2). However, the levels of anti-LKM-1 in adult AIH-2 patients and their role in liver immunopathology remain equivocal. The aim of the study was to survey the autoantibody profile and the activity of liver disease in adult patients diagnosed with AIH-2 at childhood. METHODS: The autoantibody profile of adults was compared with the autoantibodies of the pediatric period. Liver function test, Immunoglobulin G (IgG), and gamma globulins were evaluated at the AIH presentation, at the age of 18 years, and at the current adult visit. RESULTS: All ten patients tested positive for LKM-1 at least once during the pediatric period. At the adult visit, four patients lost autoantibody positivity. LKM-1 was positive in four, liver cytosol antigen 1 (LC-1) in two, soluble liver antigen in one, and antinuclear antigen in one patient. Additionally three patients with LKM 1 and one patient without LKM-1 were positive for AMA-M2 (where AMA is antimitochondrial antibodies) Immunoglobulin M (IgM). Liver function markedly improved at 18 years and adult visit compared with initial diagnosis of AIH with only a mild decrease of IgG. The six adult patients positive for at least one autoantibody had statistically lower aspartate aminotransferase (AST) and gamma glutamyltranspeptidase (GGTP) than the four patients autoantibody negative (AST: 52 vs. 88 IU/l, P < 0.05; GGTP 19 vs. 163 IU/l, P < 0.05). CONCLUSION: LKM-1 positivity is not a stable condition in all patients with AIH-2. Patients who remained autoantibody positive had better liver function tests than those who lost their positivity. The presence of AMA-M2 autoantibodies suggest that development of AIH/Primary Biliary Cirrhosis (PBC) overlap syndrome should be considered. PMID- 26676070 TI - Standards of the Polish Ultrasound Society - update. Pancreas examination. AB - Ultrasound examination of the pancreas constitutes an integral part of the abdominal ultrasound. It is mostly indicated to diagnose pain in the epigastrium, discomfort and jaundice as well as to monitor the patients with acute pancreatitis. The assessment of this organ in an ultrasound examination may be problematic due to its anatomical location and the fact that it might be covered by gastric and duodenal contents as well as due to a number of possible pathological changes, including inflammation and benign or malignant neoplasms, which require differentiation. The basis for establishing a correct diagnosis is the knowledge of the examination technique, correct pancreas structure and images of individual pathologies. This paper presents the standards of ultrasound examination published in 2011 and updated with the current knowledge. The following are discussed: preparation of the patient for the examination, abnormal lesions in the pancreas, acute pancreatitis, chronic pancreatitis, cystic lesions (benign and malignant cysts) and solid focal lesions. Ultrasound is also used to guide the drainage of fluid cisterns, abscesses and cysts. The prime role in the diagnosis and treatment of selected diseases of the upper gastrointestinal tract and parenchymal organs of the abdomen belongs to endosonography of the upper gastrointestinal tract, with the possibility to conduct a fine needle aspiration biopsy, and intraoperative or laparoscopic ultrasound. PMID- 26676072 TI - Diagnostic anatomy and diagnostics of enthesal pathologies of the rotator cuff. PMID- 26676071 TI - Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution. AB - Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose-response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution. Regression analysis did not reveal any dependence of chlorophyll and carotenoid content on traffic intensity (in 2008 and 2010-2013). Lipid peroxidation rate had different versions of paradoxical effects in 2008 and 2010 to 2012 and increased in comparison with control under an increase in pollution level in 2013. In 2010 to 2012, all dose-response dependences for total protein and thiol group content were biphasic and multiphasic paradoxical effects. In 2013, an increase in traffic intensity induced a linear reduction in protein content and an increase in thiol group level in comparison with the control. In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity. Only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly. Fluctuating asymmetry had a paradoxical effect and hormesis in 2008 and 2012, accordingly, and increased in comparison with the control under an increase in the level of pollution in 2010 to 2011. PMID- 26676073 TI - War and peace: Factor VIII and the adaptive immune response. AB - The development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitors) remains a major challenge for FVIII replacement therapy in hemophilia A patients. The adaptive immune response plays a crucial role in the development and maintenance of inhibitors. In this review, we focus on our current understanding of FVIII interactions with cells of the adaptive immune system and the phenotype of the resultant response. Additionally, we examine both current and novel FVIII tolerance induction methods that function at the level of the adaptive immune response. PMID- 26676074 TI - Applications of intraoperative ultrasound in the treatment of complicated cases of acute and chronic pancreatitis and pancreatic cancer - own experience. AB - Both acute and chronic inflammation of the pancreas often lead to complications that nowadays can be resolved using endoscopic and surgical procedures. In many cases, intraoperative ultrasound examination (IOUS) enables correct assessment of the extent of the lesion, and allows for safe surgery, while also shortening its length. AIM OF THE RESEARCH: At the authors' clinic, intraoperative ultrasound is performed in daily practice. In this paper, we try to share our experiences in the application of this particular imaging technique. RESEARCH SAMPLE AND METHODOLOGY: Intraoperative examination conducted by a surgeon who has assessed the patient prior to surgery, which enabled the surgeon to verify the initial diagnosis. The material presented in this paper includes 145 IOUS procedures performed during laparotomy due to lesions of the pancreas, 57 of which were carried out in cases of inflammatory process. RESULTS AND CONCLUSIONS: IOUS is a reliable examination tool in the evaluation of acute inflammatory lesions in the pancreas, especially during the surgery of chronic, symptomatic inflammation of the organ. The procedure allows for a correct determination of the necessary scope of the planned surgery. The examination allows for the differentiation between cystic lesions and tumors of cystic nature, dictates the correct strategy for draining, as well as validates the indications for the lesion's surgical removal. IOUS also allows the estimation of place and scope of drainage procedures in cases of overpressure in the pancreatic ducts caused by calcification of the parenchyma or choledocholitiasis in chronic pancreatitis. In pancreatic cancer, IOUS provides a verification of the local extent of tumor-like lesions, allowing for the assessment of pancreatic and lymph nodes metastasis, and indicating the presence of distant and local metastases, including the liver. IOUS significantly improves the effectiveness of intraoperative BAC aspiration or drainage of fluid reservoirs. PMID- 26676075 TI - Pan-Cardiac Cycle Fixed Mitral Valve Opening in an LVAD Patient Presenting with Hemorrhagic Shock. AB - We present the case of a patient with a HeartMate II left ventricular assist device (LVAD) who underwent an elective cholecystectomy and abruptly decompensated on postoperative day 9. We highlight the uncommon echocardiogram finding of mitral valve leaflets fixed widely open throughout the cardiac cycle during an LVAD suction event. Bedside echocardiographic confirmation of a suction event enabled the rapid diagnosis and intervention for hemorrhagic shock before blood tests and radiographic results were available. Acoustic image quality can be limited in LVAD patients, and awareness of this uncommon finding may increase specificity for the echocardiographic diagnosis of LVAD suction events. PMID- 26676076 TI - Air-Stable, Near- to Mid-Infrared Emitting Solids of PbTe/CdTe Core-Shell Colloidal quantum dots. AB - Light emitters and detectors operating in the near- and mid-infrared spectral regions are important to many applications, such as telecommunications, high resolution gas analysis, atmospheric pollution monitoring, medical diagnostics, and night vision. Various lead chalcogenides (binary, ternary, and quaternary alloys) in the form of quantum dots (QDs) or quantum wells provide narrow bandgap energies that cover the broad infrared region corresponding to wavelengths of 1 30 MUm. Here, we report an inexpensive, all-solution-based synthesis strategy to thin-film solids consisting of 5-16 nm PbTe QDs encapsulated by CdTe shells. Colloidally synthesized PbTe QDs were first converted into core-shell PbTe/CdTe QDs, and then deposited as thin films. The subsequent fusion of the CdTe shells is achieved by ligand removal and annealing in the presence of CdCl2 . Contrary to highly unstable bare PbTe QDs, PbTe/CdTe QD solids exhibit bright and stable near- to mid-infrared emission at wavelengths of 1-3 MUm, which is also retained upon prolonged storage at ambient conditions for one year. PMID- 26676077 TI - Well-Defined SiO2@P(EtOx-stat-EI) Core-Shell Hybrid Nanoparticles via Sol-Gel Processes. AB - Positively charged nanoparticles (NPs) are very interesting for biomedical and pharmaceutical applications, such as nonviral gene delivery. Here, the synthesis of SiO2 nanoparticles with a covalently grafted poly(2-ethyl-2-oxazoline) (PEtOx) shell (SiO2@PEtOx) is presented. PEtOx with a degree of polymerization of 20 and 38 is synthesized via microwave supported cationic ring-opening polymerization and subsequently end-functionalized with a triethoxysilyl linker for subsequent grafting to silica particles with hydrodynamic radii of 7, 31, and 152 nm. The resulting SiO2@PEtOx particles are characterized by using dynamic light scattering (DLS), transmission electron microscopy (TEM, cryoTEM), and scanning electron microscopy (SEM) to determine changes in particle size. Thermal gravimetrical analysis is used to quantify the amount of polymer on the silica surface. Subsequent in situ transformation of SiO2@PEtOx particles into SiO2@P(EtOx-stat-EI) (poly(2-ethyl-2-oxazoline-stat-ethylene imine) grafted silica particles) under acidic conditions inverts the surface charge from negative to positive according to zeta-potential measurements. The P(EtOx-stat EI) shell could be used for the deposition of Au NP afterward. PMID- 26676078 TI - Abnormal portal vein waveform as an indicator of constrictive pericarditis - a case report. AB - We report a case of a 17-year-old patient referred to our outpatient Doppler Department due to clinical suspicion of liver cirrhosis. The patient presented with non-specific symptoms, such as malaise, pain in the right subcostal region, peripheral oedema. Until then, diagnostic imaging, including echocardiography was inconclusive. We performed the Doppler sonography of the portal system, which revealed normal diameter of the portal vein with abnormal, phasic and markedly pulsatile waveform. Hepatic veins distention with pathological reverse flow during systole was reported. Additionally, inferior vena cava was dilated and remained unchanged through the respiratory cycle. Basing on the above image a heart disease, which had not been taken into differential diagnosis before, was suggested. The following echocardiography, together with computed tomography, enabled a diagnosis of constrictive pericarditis. Successful pericardiotomy was performed. Such a complicated diagnostics happened to demonstrate an uncommon example of the use of portal vein waveform in making the proper cardiologic diagnosis. PMID- 26676079 TI - A Study Evaluating Adherence and Compliance of Anti-rheumatic Drugs in Women Suffering from Rheumatoid Arthritis. AB - BACKGROUND: Treatment of Rheumatoid arthritis (RA) has always remained challenging, complex and associated with high level of non adherence, noncompliance in clinical practice. AIM: To evaluate the satisfaction/adherence/compliance rates of most commonly prescribed anti rheumatic drugs among Indian women. MATERIALS AND METHODS: A cross-sectional descriptive obser-vational study was undertaken to evaluate the adherence/compliance rates of most commonly prescribed anti-rheumatic drugs among women in a tertiary care teaching hospital in North India. Hundred women on anti rheumatic treatment for rheumatoid arthritis diagnosed by American College of Rheumatology (ACR) criteria were evaluated at one point analysis for adherence/compliance/satisfaction. RESULTS: Dissatisfaction rate with the anti rheumatic treatment was significantly high p<0.0001 among 68% of the women. Non compliance/ non adherence rate was also recorded very high among 52% and interrupted compliance rate was noticed among 6% of the women suffering from RA. Switch over rate to other treatment or doctors was also significantly (p<0.0001) very high among 66% of the women. Switch over to alternative treatment, treatment under quacks and intermittent self medication was recorded by 12%, 4% & 16% respectively. Among the self medication 12% of the women took corticosteroids and 4% preferred taking intermittent NSAIDs. CONCLUSION: Treatment compliance is not very good with anti-rheumatic drugs among women patients of RA due to multi factorial reasons. PMID- 26676080 TI - A novel approach to study oxidative stress in neonatal respiratory distress syndrome. AB - BACKGROUND: Respiratory distress syndrome of the neonate (neonatal RDS) is still an important problem in treatment of preterm infants. It is accompanied by inflammatory processes with free radical generation and oxidative stress. The aim of study was to determine the role of oxidative stress in the development of neonatal RDS. METHODS: Markers of oxidative stress and antioxidant activity in umbilical cord blood were studied in infants with neonatal respiratory distress syndrome with reference to healthy newborns. RESULTS: Status of markers of oxidative stress (malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxy guanosine) showed a significant increase with depleted levels of total antioxidant capacity in neonatal RDS when compared to healthy newborns. CONCLUSION: The study provides convincing evidence of oxidative damage and diminished antioxidant defenses in newborns with RDS. Neonatal RDS is characterized by damage of lipid, protein and DNA, which indicates the augmentation of oxidative stress. GENERAL SIGNIFICANCE: The identification of the potential biomarker of oxidative stress consists of a promising strategy to study the pathophysiology of neonatal RDS. PMID- 26676081 TI - Comparison of multiple protein extraction buffers for GeLC-MS/MS proteomic analysis of liver and colon formalin-fixed, paraffin-embedded tissues. AB - Formalin-fixed paraffin-embedded (FFPE) tissue specimens represent a potential valuable source of samples for clinical research. Since these specimens are banked in hospital archives, large cohorts of samples can be collected in short periods of time which can all be linked with a patients' clinical history. Therefore, the use of FFPE tissue in protein biomarker discovery studies gains interest. However, despite the growing number of FFPE proteome studies in the literature, there is a lack of a FFPE proteomics standard operating procedure (SOP). One of the challenging steps in the development of such a SOP is the ability to obtain an efficient and repeatable extraction of full length FFPE proteins. In this study, the protein extraction efficiency of eight protein extraction buffers is critically compared with GeLC-MS/MS (1D gel electrophoresis followed by in-gel digestion and LC-MS/MS). The data variation caused by using these extraction buffers was investigated since the variation is a very important aspect when using FFPE tissue as a source for biomarker detection. In addition, a qualitative comparison was made between the protein extraction efficiency and repeatability for FFPE tissue and fresh frozen tissue. PMID- 26676082 TI - A 15-Year Comparative Prospective Study of Surgical and Prosthetic Care and Aftercare of Overdenture Treatment in the Atrophied Mandible: Augmentation Versus Nonaugmentation. AB - BACKGROUND: Different treatment strategies for the atrophied mandible are described in literature. The need for long term care and aftercare for these strategies is sparsely described, however. PURPOSE: To prospectively assess the need for prosthetic and surgical care and aftercare of two implant treatment strategies for the atrophied mandible. MATERIALS AND METHODS: Forty edentulous elderly patients were randomly assigned according to a balanced allocation method to a treatment strategy: dental implants in combination with an augmentation procedure versus a nonaugmentation procedure. All surgical and prosthetic care and aftercare were scored from the first visit until 15 years after implant placement. RESULTS: Twenty elderly patients completed the 15-year follow-up. As expected, the augmentation group needed significantly more surgical time than the nonaugmentation group (338 vs 145 minutes), but the need for prosthetic care and surgical/prosthetic aftercare was comparable. Implant survival was lower in augmented mandibles (88.7% vs 98.7%, p < .05). Aftercare mainly consisted of routine inspections; the need for prosthetic adjustments was minor. Surgical aftercare was hardly needed. CONCLUSION: The only difference in the need for surgical and prosthetic (after) care was the extra time needed for performing augmentation surgery and the higher risk on implant loss in augmented mandibles. Otherwise, the need for care and aftercare was of the same magnitude. Thus, when applicable, nonaugmentation surgery is preferred as no general anesthesia is needed and the morbidity is low. PMID- 26676084 TI - Rheumatoid arthritis: Osteoclasts and ACPAs--the joint link. PMID- 26676083 TI - The dynamic evolution of rheumatology in Korea. AB - Rheumatology was first recognized as a distinct clinical specialty in Korea just 35 years ago. Young professors who were trained in rheumatology in the USA and afterwards returned to Korea contributed substantially to advances in rheumatology clinical practice, educational programmes and research activities. They also established the Korean Rheumatism Association, later renamed the Korean College of Rheumatology. These young rheumatologists had a major role not only in raising the level of clinical and scientific activities, but also in promoting academic exchanges around the Asia-Pacific region, the USA and Europe. Subsequently, Korea's rapid economic growth and high education level enabled rheumatology to advance rapidly. Today, continued efforts are required to raise the standard of clinical and basic research, to optimize clinical practice with regard to new biologic agents, to exploit personalized and targeted therapies for the rheumatic diseases, and to meet the medical demands of Korea's ageing society. PMID- 26676085 TI - Methyl and t-butyl group rotation in a molecular solid: (1)H NMR spin-lattice relaxation and X-ray diffraction. AB - We report solid state (1)H nuclear magnetic resonance spin-lattice relaxation experiments and X-ray diffractometry in 2-t-butyldimethylsilyloxy-6 bromonaphthalene. This compound offers an opportunity to simultaneously investigate, and differentiate between, the rotations of a t-butyl group [C(CH3)3] and its three constituent methyl groups (CH3) and, simultaneously, a pair of 'lone' methyl groups (attached to the Si atom). The solid state (1)H relaxation experiments determine activation energies for these rotations. We review the models for the dynamics of both 'lone' methyl groups (ones whose rotation axes do not move on the NMR time scale) and models for the dynamics of the t-butyl group and its constituent methyl groups (whose rotation axes reorient on the NMR time scale as the t-butyl group rotates). PMID- 26676087 TI - Response to the comment on "Halogenated indigo dyes: A likely source of 1,3,6,8 tetrabromocarbazole and some other halogenated carbazoles in the environment". PMID- 26676086 TI - Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats. AB - AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-alpha increase (P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue iNOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups (P < 0.05). CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model, possibly via reduction of MPO, TNF-alpha, and iNOS levels. PMID- 26676088 TI - Development of the shoulder girdle musculature. AB - The muscles of the shoulder region are important for movements of the upper limbs and for stabilizing the girdle elements by connecting them to the trunk. They have a triple embryonic origin. First, the branchiomeric shoulder girdle muscles (sternocleidomastoideus and trapezius muscles) develop from the occipital lateral plate mesoderm using Tbx1 over the course of this development. The second population of cells constitutes the superficial shoulder girdle muscles (pectoral and latissimus dorsi muscles), which are derived from the wing premuscle mass. This muscle group undergoes a two-step development, referred to as the "in-out" mechanism. Myogenic precursor cells first migrate anterogradely into the wing bud. Subsequently, they migrate in a retrograde manner from the wing premuscle mass to the trunk. SDF-1/CXCR4 signaling is involved in this outward migration. A third group of shoulder muscles are the rhomboidei and serratus anterior muscles, which are referred to as deep shoulder girdle muscles; they are thought to be derived from the myotomes. It is, however, not clear how myotome cells make contact to the scapula to form these two muscles. In this review, we discuss the development of the shoulder girdle muscle in relation to the different muscle groups. PMID- 26676089 TI - Anterolateral Portal Is Less Painful than Superolateral Portal in Knee Intra Articular Injection. AB - PURPOSE: Intra-articular knee injections are commonly performed in clinical practice for treating various knee joint disorders such as osteoarthritis and rheumatoid arthritis. When selecting the portal for injection, not only intra articular needle accuracy but also procedural pain should be taken into consideration. The purpose of this study was to determine whether injection through anterolateral portal provokes less pain and provides better pain relief compared to superolateral portal. MATERIALS AND METHODS: A total of 60 patients with primary osteoarthritis of the knee receiving intra-articular injections were randomized into 2 groups according to the type of portal approach; anterolateral or superolateral. All patients received hyaluronic acid (20 mg) and triamcinolone (40 mg) as the first injection followed by second and third injections of hyaluronic acid on a weekly basis. Underlying knee pain, procedural pain, and knee pain at 4 weeks were evaluated using visual analogue scale (VAS). RESULTS: Injection through anterolateral portal provoked less pain (VAS, 1.5+/-1.3) than the superolateral portal (VAS, 1.5 vs. 2.7; p=0.004). No differences were found in the degree of pain relief at weeks between the two groups (p=0.517). CONCLUSIONS: We recommend the use of anterolateral portal for intra-articular knee injection as it provokes less pain and comparably short-term pain relief than the superolateral portal. PMID- 26676090 TI - Validation of an Albuminuria Self-assessment Tool in the Multi-Ethnic Study of Atherosclerosis. AB - OBJECTIVE: We previously developed an 8-item self-assessment tool to identify individuals with a high probability of having albuminuria. This tool was developed and externally validated among non-Hispanic Whites and non-Hispanic Blacks. We sought to validate it in a multi-ethnic cohort that also included Hispanics and Chinese Americans. DESIGN: This is a cross-sectional study. SETTING: Data were collected using standardized questionnaires and spot urine samples at a baseline examination in 2000-2002. The 8 items in the self assessment tool include age, race, gender, current cigarette smoking, history of diabetes, hypertension, or stroke, and self-rated health. PARTICIPANTS: Of 6,814 community-dwelling adults aged 45-84 years participating in the Multi-Ethnic Study of Atherosclerosis (MESA), 6,542 were included in the primary analysis. MAIN OUTCOME MEASURES: Albuminuria was defined as urine albumin-to-creatinine ratio >= 30 mg/g at baseline. RESULTS: Among non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, the prevalence of albuminuria was 6.0%, 11.3%, 11.6%, and 10.8%, respectively. The c-statistic for discriminating participants with and without albuminuria was .731 (95% CI: .692, .771), .728 (95% CI: .687, .761), .747 (95% CI: .709, .784), and .761 (95% CI: .699, .814) for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, respectively. The self-assessment tool over-estimated the probability of albuminuria for non-Hispanic Whites and Blacks, but was well-calibrated for Hispanics and Chinese Americans. CONCLUSIONS: The albuminuria self-assessment tool maintained good test characteristics in this large multi-ethnic cohort, suggesting it may be helpful for increasing awareness of albuminuria in an ethnically diverse population. PMID- 26676091 TI - 3D Micropillars Guide the Mechanobiology of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. AB - 3D micropillars generated by photolithography are used as a platform to probe by atomic force microscopy the mechanodynamics of human induced pluripotent stem cell-derived cardiomyocytes. 3D micropillars guide subcellular cytoskeletal modifications of cardiomyocytes and lead to biochemical changes altering beating rate, stiffness, and calcium dynamics of the cells. PMID- 26676092 TI - Ultrasound-assisted aspiration of loculated pneumothorax: A new technique. AB - In this report, we describe a new sonographic (US) technique that can assist in the aspiration of a loculated pneumothorax. Patients may develop loculated pneumothorax as a result of such conditions as pleural malignancy or pleural infection or after undergoing thoracic surgery. Often the loculated pneumothorax is outside of safe areas, and chest tubes need to be placed near vital structures. This report presents the cases of three patients with iatrogenic loculated pneumothorax that required aspiration. We used US to assist in the placement of chest tubes, and we describe our technique of US-assisted aspiration of loculated pneumothorax. The procedure is a new approach to a common problem in chest medicine that may increase the safety of treatment. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:326-330, 2016. PMID- 26676093 TI - Trocar types in laparoscopy. AB - BACKGROUND: Laparoscopic surgery has led to great clinical improvements in many fields of surgery; however, it requires the use of trocars, which may lead to complications as well as postoperative pain. The complications include intra abdominal vascular and visceral injury, trocar site bleeding, herniation and infection. Many of these are extremely rare, such as vascular and visceral injury, but may be life-threatening; therefore, it is important to determine how these types of complications may be prevented. It is hypothesised that trocar related complications and pain may be attributable to certain types of trocars. This systematic review was designed to improve patient safety by determining which, if any, specific trocar types are less likely to result in complications and postoperative pain. OBJECTIVES: To analyse the rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy, regardless of the condition. SEARCH METHODS: Two experienced librarians conducted a comprehensive search for randomised controlled trials (RCTs) in the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, CDSR and DARE (up to 26 May 2015). We checked trial registers and reference lists from trial and review articles, and approached content experts. SELECTION CRITERIA: RCTs that compared rates of trocar-related complications and postoperative pain for different trocar types used in people undergoing laparoscopy. The primary outcomes were major trocar-related complications, such as mortality, conversion due to any trocar-related adverse event, visceral injury, vascular injury and other injuries that required intensive care unit (ICU) management or a subsequent surgical, endoscopic or radiological intervention. Secondary outcomes were minor trocar-related complications and postoperative pain. We excluded trials that studied non conventional laparoscopic incisions. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted the study selection, risk of bias assessment and data extraction. We used GRADE to assess the overall quality of the evidence. We performed sensitivity analyses and investigation of heterogeneity, where possible. MAIN RESULTS: We included seven RCTs (654 participants). One RCT studied four different trocar types, while the remaining six RCTs studied two different types. The following trocar types were examined: radially expanding versus cutting (six studies; 604 participants), conical blunt-tipped versus cutting (two studies; 72 participants), radially expanding versus conical blunt tipped (one study; 28 participants) and single-bladed versus pyramidal-bladed (one study; 28 participants). The evidence was very low quality: limitations were insufficient power, very serious imprecision and incomplete outcome data. Primary outcomesFour of the included studies reported on visceral and vascular injury (571 participants), which are two of our primary outcomes. These RCTs examined 473 participants where radially expanding versus cutting trocars were used. We found no evidence of a difference in the incidence of visceral (Peto odds ratio (OR) 0.95, 95% confidence interval (CI) 0.06 to 15.32) and vascular injury (Peto OR 0.14, 95% CI 0.0 to 7.16), both very low quality evidence. However, the incidence of these types of injuries were extremely low (i.e. two cases of visceral and one case of vascular injury for all of the included studies). There were no cases of either visceral or vascular injury for any of the other trocar type comparisons. No studies reported on any other primary outcomes, such as mortality, conversion to laparotomy, intensive care admission or any re intervention. Secondary outcomesFor trocar site bleeding, the use of radially expanding trocars was associated with a lower risk of trocar site bleeding compared to cutting trocars (Peto OR 0.28, 95% CI 0.14 to 0.54, five studies, 553 participants, very low quality evidence). This suggests that if the risk of trocar site bleeding with the use of cutting trocars is assumed to be 11.5%, the risk with the use of radially expanding trocars would be 3.5%. There was insufficient evidence to reach a conclusion regarding other trocar types, their related complications and postoperative pain, as no studies reported data suitable for analysis. AUTHORS' CONCLUSIONS: Data were lacking on the incidence of major trocar-related complications, such as visceral or vascular injury, when comparing different trocar types with one another. However, caution is urged when interpreting these results because the incidence of serious complications following the use of a trocar was extremely low. There was very low quality evidence for minor trocar-related complications suggesting that the use of radially expanding trocars compared to cutting trocars leads to reduced incidence of trocar site bleeding. These secondary outcomes are viewed to be of less clinical importance.Large, well-conducted observational studies are necessary to answer the questions addressed in this review because serious complications, such as visceral or vascular injury, are extremely rare. However, for other outcomes, such as trocar site herniation, bleeding or infection, large observational studies may be needed as well. In order to answer these questions, it is advisable to establish an international network for recording these types of complications following laparoscopic surgery. PMID- 26676094 TI - Laparoscopic Excision of Retroperitoneal Schwannoma. AB - Schwannomas are tumours that arise from the myelin sheath of the nerves. A very unusual location for schwannoma is the retro peritoneal areas (less than 2%). We present herewith a patient who had a 4x5cm Schwannoma arising from the nerve root of L2 on the right side, which presented as a lump in the psoas major muscle. This was treated by total laparoscopic excision after splitting open the psoas major. In the published english medical literature we could find only 16 cases of laparoscopic resection of retroperitoneal schwannoma and we believe ours to be the first case that was done through a psoas muscle split technique. Technical and histopathological details are discussed elaborately in this article. PMID- 26676095 TI - Medium-sized Au40(SR)24 and Au52(SR)32 nanoclusters with distinct gold-kernel structures and spectroscopic features. AB - We have analyzed the structures of two medium-sized thiolate-protected gold nanoparticles (RS-AuNPs) Au40(SR)24 and Au52(SR)32 and identified the distinct structural features in their Au kernels [Sci. Adv., 2015, 1, e1500425]. We find that both Au kernels of the Au40(SR)24 and Au52(SR)32 nanoclusters can be classified as interpenetrating cuboctahedra. Simulated X-ray diffraction patterns of the RS-AuNPs with the cuboctahedral kernel are collected and then compared with the X-ray diffraction patterns of the RS-AuNPs of two other prevailing Au kernels identified from previous experiments, namely the Ino-decahedral kernel and icosahedral kernel. The distinct X-ray diffraction patterns of RS-AuNPs with the three different types of Au-kernels can be utilized as signature features for future studies of structures of RS-AuNPs. Moreover, the simulated UV/Vis absorption spectra and Kohn-Sham orbital energy-level diagrams are obtained for the Au40(SR)24 and Au52(SR)32, on the basis of time-dependent density functional theory computation. The extrapolated optical band-edges of Au40(SR)24 and Au52(SR)32 are 1.1 eV and 1.25 eV, respectively. The feature peaks in the UV/Vis absorption spectra of the two clusters can be attributed to the d -> sp electronic transition. Lastly, the catalytic activities of the Au40(SR)24 and Au52(SR)32 are examined using CO oxidation as a probe. Both medium-sized thiolate protected gold clusters can serve as effective stand-alone nanocatalysts. PMID- 26676096 TI - Target Identification of Compounds from a Cell Viability Phenotypic Screen Using a Bead/Lysate-Based Affinity Capture Platform. AB - The pharmaceutical industry has been continually challenged by dwindling target diversity. To obviate this trend, phenotypic screens have been adopted, complementing target-centric screening approaches. Phenotypic screens identify drug leads using clinically relevant and translatable mechanisms, remaining agnostic to targets. While target anonymity is advantageous early in the drug discovery process, it poses challenges to hit progression, including the development of backup series, retaining desired pharmacology during optimization, discovery of markers, and understanding mechanism-driven toxicity. Consequently, significant effort has been expended to elaborate the targets and mechanisms at work for promising screening hits. Affinity capture is commonly leveraged, where the compounds are linked to beads and targets are abstracted from cell homogenates. This technique has proven effective for identifying targets of kinase, PARP, and HDAC inhibitors, and examples of new targets have been reported. Herein, a three-pronged approach to target deconvolution by affinity capture is described, including the implementation of a uniqueness index that helps discriminate between bona fide targets and background. The effectiveness of this approach is demonstrated using characterized compounds that act on known and noncanonical target classes. The platform is subsequently applied to phenotypic screening hits, identifying candidate targets. The success rate of bead-based affinity capture is discussed. PMID- 26676097 TI - An AlphaScreen Assay for the Discovery of Synthetic Chemical Inhibitors of Glucagon Production. AB - Glucose homeostasis is primarily controlled by two opposing hormones, insulin and glucagon, and diabetes results when insulin fails to inhibit glucagon action. Recent efforts to control glucagon in diabetes have focused on antagonizing the glucagon receptor, which is effective in lowering blood glucose levels but leads to hyperglucogonemia in rodents. An alternative strategy would be to control glucagon production with small molecules. In pursuit of this goal, we developed a homogeneous AlphaScreen assay for measuring glucagon in cell culture media and used this in a high-throughput screen to discover synthetic compounds that inhibited glucagon secretion from an alpha cell-like cell line. Some of these compounds inhibited transcription of the glucagon gene. PMID- 26676098 TI - High-Throughput Mass Spectrometric Analysis of Covalent Protein-Inhibitor Adducts for the Discovery of Irreversible Inhibitors: A Complete Workflow. AB - We have implemented a solid-phase extraction based time-of-flight mass spectrometer system in combination with novel informatics to rapidly screen and characterize the covalent binding of different irreversible inhibitors to intact proteins. This high-throughput screening platform can be used to accurately detect and quantitate the extent of formation of different covalent protein inhibitor adducts between electrophilic inhibitors and nucleophilic residues such as cysteine or lysine. For a representative 19.5 kDa protein, the analysis time is approximately 20 s per sample, including an efficient sample loading and desalting step. Accurate protein masses are measured (+/-0.5 amu of the theoretical molecular weight; measured precision of +/-0.02 amu). The fraction of protein reacted with an electrophilic compound is determined relative to an unmodified protein control. A key element of the workflow is the automated identification and quantitation of the expected masses of covalent protein inhibitor adducts using a custom routine that obviates the need to manually inspect each individual spectrum. Parallel screens were performed on a library of approximately 1000 acrylamide containing compounds (different structures and reactivities) using the solid-phase extraction mass spectrometry based assay and a fluorescence based thiol-reactive probe assay enabling comparison of false positives and false negatives between these orthogonal screening approaches. PMID- 26676099 TI - Incisal Apical Root Resorption Evaluation after Low-Friction Orthodontic Treatment Using Two-Dimensional Radiographic Imaging and Trigonometric Correction. AB - BACKGROUND: Root resorption shall be taken into consideration during every orthodontic treatment, and it can be effected by the use of different techniques, such as the application of low friction mechanics. However, its routinely assessment on orthopantomography has limitations related to distortions and changes in dental inclination. AIM: The aim of this investigation was to evaluate the severity of apical root resorption of maxillary and mandibular incisors after low-friction orthodontic treatment, using the combination of panoramic and lateral radiographs, and applying a trigonometric correction. SETTINGS AND DESIGN: A hospital based Retrospective study at the orthodontic Department (Dental School, University of Brescia, Spedali Civili di Brescia, Brescia, Italy). MATERIALS AND METHODS: Ninety-three subjects (53 females and 40 males; mean age, 14 years) with mild teeth crowding were treated without extractions by the same operator using a low-friction fixed appliance following an integrated straight wire (ISW) protocol. The pre- and post-treatment tooth lengths of the maxillary and mandibular incisors were measured on panoramic radiographs. A trigonometric factor of correction for the pre-treatment length was calculated based on the difference between the pre and post-treatment incisal inclination on lateral cephalograms. STATISTICAL ANALYSIS: The changes in lengths were investigated using the Student's t-test for paired values (p<0.05). RESULTS: Maxillary central incisors showed no changes (0.3%, 0.6%), maxillary lateral incisors showed a small increase (1.4%, 1.8%) that was attributed to the completion of root development in younger patients, mandibular central and lateral incisors underwent slight resorption (-3.1%, -3.4%). A statistically significant difference was found for the mandibular incisors but not for the maxillary ones. CONCLUSION: In patients with mild crowding and consequent low amount of root movement, a low-friction orthodontic treatment can lead to slight apical root resorption, mainly involving lower incisors. The use of a trigonometric correction in the panoramic radiograph analysis may reduce the limitations of this 2D evaluation. PMID- 26676100 TI - Giant basal cell carcinoma of the face: surgical management and challenges for reconstruction. AB - BACKGROUND: Giant basal cell carcinoma, in which the tumour measures 5 cm or greater in diameter, is a very rare skin malignancy that accounts for less than 1 per cent of all basal cell tumours. Very few studies have reported on the incidence, resection and reconstruction of this lesion worldwide. METHODS: In total, 17 patients with giant basal cell carcinoma of the head and neck region underwent surgical excision and reconstruction at our hospital. Medical charts were retrospectively reviewed and analysed. RESULTS: The lesion was usually in the forehead, eyelid, lips or nasal-cheek region. The greatest diameter ranged from 5 to 11 cm, with 5-6 cm being the most common size at the time of presentation. All patients had their tumour resected and reconstructed in a single-stage procedure, mostly with a local advancement flap, and with no post operative flap failure. CONCLUSION: Giant basal cell carcinoma of the head and neck can be successfully treated with a local flap in a single-stage approach. PMID- 26676102 TI - The Risk of Cancer in Patients With Psoriasis: A Population-Based Cohort Study in the Health Improvement Network. AB - IMPORTANCE: The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the use of immune-suppressive treatments and UV therapies, and the increased prevalence of comorbid, well-established risk factors for cancer, such as smoking and obesity, all of which may increase the risk of carcinogenesis. OBJECTIVE: To compare the overall risk of cancer, and specific cancers of interest, in patients with psoriasis compared with patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of patients ages 18 to 89 years with no medical history of human immunodeficiency virus, cancer, organ transplants, or hereditary disease (albinism and xeroderma pigmentosum), prior to the start date, conducted using The Health Improvement Network, a primary care medical records database in the United Kingdom. The data analyzed had been collected prospectively from 2002 through January 2014. The analysis was completed in August 2015. EXPOSURES OF INTEREST: Patients with at least 1 diagnostic code for psoriasis were classified as having moderate-to-severe disease if they had been prescribed psoralen, methotrexate, cyclosporine, acitretin, adalimumab, etanercept, infliximab, or ustekinumab or phototherapy for psoriasis. Patients were classified as having mild disease if they never received treatment with any of these agents. MAIN OUTCOMES AND MEASURES: Incident cancer diagnosis. RESULTS: A total of 937,716 control group patients without psoriasis, matched on date and practice visit, and 198,366 patients with psoriasis (186,076 with mild psoriasis and 12,290 with moderate-to-severe disease) were included in the analysis. The adjusted hazard ratios (aHRs) with 95% CIs for any incident cancer excluding nonmelanoma skin cancer (NMSC) were 1.06 (95% CI, 1.02-1.09), 1.06 (95% CI, 1.02 1.09), and 1.08 (95% CI, 0.96-1.22) in the overall, mild, and severe psoriasis group. The aHRs for incident lymphoma were 1.34 (95% CI, 1.18-1.51), 1.31 (95% CI, 1.15-1.49), and 1.89 (95% CI, 1.25-2.86); for NMSC, 1.12 (95% CI, 1.07-1.16), 1.09 (95% CI, 1.05-1.13), and 1.61 (95% CI, 1.42-1.84); and for lung cancer, 1.15 (95% CI, 1.03-1.27), 1.12 (95% CI, 1.01-1.25), and 1.62 (95% CI, 1.16-2.28) in the overall, mild, and severe psoriasis groups, respectively. No significant association was seen with cancer of the breast, colon, prostate, or leukemia. CONCLUSIONS AND RELEVANCE: The association between psoriasis and cancer, albeit small, was present in our cohort of patients with psoriasis. This association was primarily driven by NMSC, lymphoma, and lung cancer. PMID- 26676103 TI - Transforming growth factor-beta2 increases the capacity of retinal pigment epithelial cells to induce the generation of regulatory T cells. AB - The present study investigated the underlying mechanism of the induction of regulatory T cells (Tregs) by retinal pigment epithelial (RPE) cells and the characteristics of these Tregs. Human RPE cells were cultured in the presence or absence of transforming growth factor-beta 2 (TGF-beta2), and reverse transcription quantitative PCR was performed to determine the mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear factor erythroid 2-related factor (Nrf2). Supernatants of RPE cell cultures were added to CD4+ T cells to induce Tregs. The RPE-induced Tregs were purified by two-step magnetic cell sorting. The natural Tregs were isolated from the peripheral blood mononuclear cells of healthy volunteers. Purified CD4+ CD25- T cells (2 x 10(5)/well) were cultured alone or with Tregs (various densities, natural or RPE-induced). The proliferation of CD4+ CD25- T cells was determined by 3H-thymidine incorporation. After 24 h of stimulation with TGF-beta2, the mRNA expression of IDO in RPE cells was upregulated. The highest level of IDO mRNA expression was reached after 72 h of stimulation with TGF-beta2. However, the Nrf2 mRNA expression was slightly decreased after 24 h of stimulation with TGF-beta2 and significantly increased after 48-72 h of TGF-beta2 stimulation. Increased levels of CD25 expression were observed on CD4+ T cells exposed to supernatants of RPE cell cultures treated with TGF-beta2 and recombinant interleukin-2. The RPE-induced Tregs were more effective at suppressing the proliferation of CD4+ CD25- T cells compared with native Tregs. These findings suggested that IDO may be a signaling protein in RPE cells which is implicated in the induction of Tregs. RPE-induced Tregs have the potential to be applied for immunotherapy for ocular inflammatory diseases. PMID- 26676104 TI - Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area. AB - BACKGROUND: Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. AIM: Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. MATERIALS AND METHODS: Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. RESULTS: Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. CONCLUSION: This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas. PMID- 26676105 TI - A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot. AB - Congenital heart disease (CHD), the most common type of developmental abnormality, is associated with substantial morbidity and mortality in humans worldwide. The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed 2 (HAND2), has been demonstrated to be crucial for normal cardiovascular development in animal models. However, whether a genetically defective HAND2 contributes to congenital heart disease (CHD) in humans remains to be explored. In this study, the entire coding region and splicing boundaries of the HAND2 gene were sequenced in a cohort of 145 unrelated patients with CHD. A total of 200 unrelated, ethnically-matched healthy individuals used as controls were also genotyped for HAND2. The functional effect of the mutant HAND2 was characterized in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous HAND2 mutation, p.L47P, was identified in a patient with tetralogy of Fallot (TOF). The misense mutation, which altered the amino acid conserved evolutionarily among species, was absent in 400 control chromosomes. Functional analyses unveiled that the mutant HAND2 had a significantly decreased transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation between HAND2 and GATA4 or NKX2.5, other two cardiac key transcription factors involved in the pathogenesis of CHD. To the best of our knowledge, this study is the first to report the association of a HAND2 loss-of function mutation with an increased vulnerability to TOF in humans, which provides novel insight into the molecular mechanism underpinning CHD, suggesting potential implications for the genetic counseling of families with CHD. PMID- 26676106 TI - Mixed emotions: Sensitivity to facial variance in a crowd of faces. AB - The visual system automatically represents summary information from crowds of faces, such as the average expression. This is a useful heuristic insofar as it provides critical information about the state of the world, not simply information about the state of one individual. However, the average alone is not sufficient for making decisions about how to respond to a crowd. The variance or heterogeneity of the crowd--the mixture of emotions--conveys information about the reliability of the average, essential for determining whether the average can be trusted. Despite its importance, the representation of variance within a crowd of faces has yet to be examined. This is addressed here in three experiments. In the first experiment, observers viewed a sample set of faces that varied in emotion, and then adjusted a subsequent set to match the variance of the sample set. To isolate variance as the summary statistic of interest, the average emotion of both sets was random. Results suggested that observers had information regarding crowd variance. The second experiment verified that this was indeed a uniquely high-level phenomenon, as observers were unable to derive the variance of an inverted set of faces as precisely as an upright set of faces. The third experiment replicated and extended the first two experiments using method-of constant-stimuli. Together, these results show that the visual system is sensitive to emergent information about the emotional heterogeneity, or ambivalence, in crowds of faces. PMID- 26676107 TI - Colorectal Cancer: Personalized Therapy. AB - BACKGROUND: Colorectal cancer (CRC) is the second most common type of cancer in the Western world. The treatment of this disease has evolved greatly, particularly for patients with metastatic disease. The advent of combination chemotherapy plus targeted agents has led to more curative resections and improved survival rates in these patients. A deeper understanding of the mechanisms of tumorigenesis has facilitated tumor characterization, prognosis and patient stratification, bringing us one step closer towards personalized medicine. SUMMARY: There are two main pathways of CRC development: (1) chromosomal instability, also known as the classical adenoma-carcinoma sequence, and (2) microsatellite instability, caused by a defective mismatch repair (dMMR) system. Analysis of these pathways has uncovered key prognostic and predictive biomarkers to guide patient selection and treatment strategy. This review summarizes the current treatment regimens and recent advances in the personalized therapy of CRC. KEY MESSAGE: Understanding of the mechanisms of CRC pathogenesis has led to new developments in tumor characterization, patient stratification, prognosis and treatment, bringing us closer to personalized therapy. PRACTICAL IMPLICATIONS: In the adjuvant setting, the treatment decision is driven by clinical and histopathological factors. dMMR status is one of the most robust positive prognostic factors in resected colon cancer. More and more guidelines recommend refraining from adjuvant chemotherapy in patients with dMMR. In the metastatic setting, the introduction of effective compounds, including agents that target the epidermal growth factor receptor and vascular endothelial growth factor pathways, has significantly improved survival. The presence of wild-type KRAS and NRAS (all RAS) is a positive predictive factor for epidermal growth factor receptor antibody treatment. Therefore, analysis of all RAS status is recommended for all patients with metastatic disease prior to the initiation of first-line chemotherapy. PMID- 26676108 TI - Percutaneous Treatment of Splenic Cystic Echinococcosis: Results of 12 Cases. AB - PURPOSE: Cystic echinococcosis (CE) in the spleen is a rare disease even in endemic regions. The aim of this study was to examine the efficacy of percutaneous treatment for splenic CE. MATERIALS AND METHODS: Twelve patients (four men, eight women) with splenic CE were included in this study. For percutaneous treatment, CE1 and CE3A splenic hydatid cysts were treated with either the PAIR (puncture, aspiration, injection, respiration) technique or the catheterization technique. RESULTS: Eight of the hydatid cysts were treated with the PAIR technique and four were treated with catheterization. The volume of all cysts decreased significantly during the follow-up period. No complication occurred in seven of 12 patients. Abscess developed in four patients. Two patients underwent splenectomy due to cavity infection developed after percutaneous treatment, while the spleen was preserved in 10 of 12 patients. Total hospital stay was between 1 and 18 days. Hospital stay was longer and the rate of infection was higher in the catheterization group. Follow-up period was 5 117 months (mean, 44.8 months), with no recurrence observed. CONCLUSION: The advantages of the percutaneous treatment are its minimal invasive nature, short hospitalization duration, and its ability to preserve splenic tissue and function. As the catheterization technique is associated with higher abscess risk, we suggest that the PAIR procedure should be the first percutaneous treatment option for splenic CE. PMID- 26676109 TI - Sharp Central Venous Recanalization in Hemodialysis Patients: A Single Institution Experience. AB - PURPOSE: We report our institutional experience with sharp central venous recanalization in chronic hemodialysis patients who failed standard techniques. MATERIALS AND METHODS: Since January 2014, a series of seven consecutive patients (four males and three females), mean age 35 years (18-65 years), underwent sharp central venous recanalization. Indications included obtaining hemodialysis access (n = 6) and restoration of superior vena cava (SVC) patency to alleviate occlusion symptoms and restore fistula function (n = 1). The transseptal needle was used for sharp recanalization in six patients, while it could not be introduced in one patient due to total occlusion of the inferior vena cava. Instead, transmediastinal SVC access using Chiba needle was obtained. RESULTS: Technical success was achieved in all cases. SVC recanalization achieved symptoms' relief and restored fistula function in the symptomatic patient. One patient underwent arteriovenous fistula creation on the recanalized side 3 months after the procedure. The remaining catheters were functional at median follow-up time of 9 months (1-14 months). Two major complications occurred including a right hemothorax and a small hemopericardium, which were managed by covered stent placement across the perforated SVC. CONCLUSION: Sharp central venous recanalization using the transseptal needle is feasible technique in patients who failed standard recanalization procedures. The potential high risk of complications necessitates thorough awareness of anatomy and proper technical preparedness. PMID- 26676110 TI - Arterial Embolization in the Management of Mesenteric Bleeding Secondary to Blunt Abdominal Trauma. AB - INTRODUCTION: Mesenteric bleeding is a rare but potentially life-threatening complication of blunt abdominal trauma. It can induce active hemorrhage and a compressive hematoma leading to bowel ischemia. Emergency laparotomy remains the gold standard treatment. We aimed to study the effectiveness and complications of embolization in patients with post-traumatic mesenteric bleeding. MATERIALS AND METHODS: The medical records of 7 consecutive patients with active mesenteric bleeding treated by embolization in a level-one trauma center from 2007 to 2014 were retrospectively reviewed. All patients presented with active mesenteric bleeding on CT scans without major signs of intestinal ischemia. We focused on technical success, clinical success, and the complications of embolization. RESULTS: Six endovascular procedures were successful in controlling hemorrhage but 1 patient had surgery to stop associated arterial and venous bleeding. One patient suffered from bowel ischemia, a major complication of embolization, which was confirmed by surgery. No acute renal failure was noted after angiography. For 1 patient we performed combined management as the endovascular approach allowed an easier surgical exploration. CONCLUSION: In mesenteric trauma with active bleeding, embolization is a valuable alternative to surgery and should be considered, taking into account the risk of bowel ischemia. PMID- 26676111 TI - Core value of laparoscopic colorectal surgery. AB - Since laparoscopy was first used in cholecystectomy in 1987, it has developed quickly and has been used in most fields of traditional surgery. People have now accepted its advantages like small incision, quick recovery, light pain, beauty and short hospital stays. In early times, there are still controversies about the application of laparoscopy in malignant tumor treatments, especially about the problems of oncology efficacy, incision implantation and operation security. However, these concerns have been fully eliminated by evidences on the basis of evidence-basis medicine. In recent years, new minimally invasive technologies are appearing continually, but they still have challenges and may increase the difficulties of radical dissection and the risks of potential complications, so they are confined to benign or early malignant tumors. The core value of the laparoscopic technique is to ensure the high quality of tumor's radical resection and less complications. On the basis of this, it is allowed to pursue more minimally invasive techniques. Since the development of laparoscopic colorectal surgery is rapid and unceasing, we have reasons to believe that laparoscopic surgery will become gold standard for colorectal surgery in the near future. PMID- 26676113 TI - The dark side of ID8-Luc2: pitfalls for luciferase tagged murine models for ovarian cancer. AB - Reliable mouse models are key in the discovery and development of novel anticancer treatments. Non-invasive monitoring techniques such as bioluminescence imaging (BLI) are useful tools to determine tumor engraftment and evaluate tumor growth. However, the development of ascites in ovarian cancer mouse models leads to possible difficulties. Ascites can interfere with the set-up of correct end points and can interfere with the evaluation of tumor volume using BLI. We provide optimized euthanasia criteria and in vivo data underlining the pitfalls of BLI. PMID- 26676112 TI - AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease. AB - Angiotensin II, which is the main effector of the renin-angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3. PMID- 26676114 TI - Low zinc levels is associated with increased inflammatory activity but not with atherosclerosis, arteriosclerosis or endothelial dysfunction among the very elderly. AB - BACKGROUND: Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall. METHODS: Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated. RESULTS: There was no significant difference in clinical or laboratorial data between subjects grouped according to plasma zinc tertile, except for CRP (p = 0.01) and blood leukocytes (p = 0.002), of which levels were higher in the upper tertiles. The average daily intake of zinc was not significantly correlated with zinc or CRP plasma levels. The plasma zinc/zinc intake ratio was inversely correlated with plasma CRP levels (- 0.18; p = 0.01). There was no significant difference between the plasma zinc tertiles and FMD, carotid intima-media thickness, coronary calcium score, carotid plaque presence, remodeled noncalcified coronary plaques, or low-attenuation noncalcified coronary plaques. CONCLUSION: Although plasma zinc level is inversely related to systemic inflammatory activity, its plasma levels of daily intake are not associated to alterations in structure or function of the arterial wall. GENERAL SIGNIFICANCE: In the very elderly plasma concentrations or daily intake of zinc is not related to endothelial dysfunction, arteriosclerosis or atherosclerotic burden at coronary or carotid arteries. PMID- 26676116 TI - Letter to the Editor: Medicolegal Sidebar: Informed Consent in the Information Age. PMID- 26676115 TI - Differences in the control of basal L-type Ca(2+) current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes. AB - beta-adrenergic receptors (beta-ARs) mediate the positive inotropic effects of catecholamines by cAMP-dependent phosphorylation of the L-type Ca(2+) channels (LTCCs), which provide Ca(2+) for the initiation and regulation of cell contraction. The overall effect of cAMP-modulating agents on cardiac calcium current (I Ca,L) and contraction depends on the basal activity of LTCCs which, in turn, depends on the basal activities of key enzymes involved in the cAMP signaling cascade. Our current work is a comparative study demonstrating the differences in the basal activities of beta-ARs, adenylyl cyclase, phosphodiesterases, phosphatases, and LTCCs in the frog and rat ventricular and human atrial myocytes. The main conclusion is that the basal I Ca,L, and consequently the contractile function of the heart, is secured from unnecessary elevation of its activity and energy consumption at the several "checking-points" of cAMP-dependent signaling cascade and the loading of these "checking-points" may vary in different species and tissues. PMID- 26676117 TI - Not the Last Word: Fibromyalgia is Real. PMID- 26676118 TI - CORR ((r)) Insights: Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management after THA: A Network Meta-analysis. PMID- 26676119 TI - CORR Insights((r)): Gamma Radiation Sterilization Reduces the High-cycle Fatigue Life of Allograft Bone. PMID- 26676120 TI - CORR Insights((r)): Custom Acetabular Cages Offer Stable Fixation and Improved Hip Scores for Revision THA With Severe Bone Defects. PMID- 26676121 TI - Everyone has a role in building a health creating society. PMID- 26676122 TI - Isolation and Primary Culture of Murine Podocytes with Proven Origin. AB - Genetic studies on hereditary kidney diseases and in vivo experimental model studies have revealed a critical role for the podocyte in glomerular function and disease. Primary podocyte cultures as well as immortalized podocyte cell lines have been used extensively to study podocyte function. Although, primary cells often more closely resemble the in vivo cells, they may have only a finite replicative life span before they reach senescence. Therefore, the success of studies using primary cell cultures depends on standardized isolation and culture protocols that allow reproducible generation of stable primary cultures.This chapter describes the isolation of primary podocytes with a proven origin using the novel technology of cell-specific genetic tagging. Podocytes are isolated from glomeruli from a podocyte-specific transgenic reporter mouse. The podocyte specific reporter gene beta-galactosidase is used to identify and specifically isolate the labeled podocytes from other glomerular cells by FACS. PMID- 26676123 TI - Propagation and Culture of Human Renal Fibroblasts. AB - The renal fibroblast and phenotypically related myofibroblast are universally present in all forms of progressive kidney disease. The in vitro study of the fibroblast, its behavior, and factors affecting its activity is therefore key to understanding both its role and significance. In this protocol, we describe a reproducible method for selective propagation and culture of primary human renal fibroblasts from the human kidney cortex. Techniques for their isolation, subculture, characterization, and cryogenic storage and retrieval are described in detail. PMID- 26676125 TI - Rat Models of Acute and/or Chronic Peritoneal Injuries Including Peritoneal Fibrosis and Peritoneal Dialysis Complications. AB - Peritoneal injury is a major cause of discontinuation from long-term peritoneal dialysis. However, the precise mechanisms underlying such injury remain unclear. Suitable animal models of peritoneal injury may be useful to analyze pathogenic mechanisms and facilitate the development of therapeutic approaches. We describe herein two rat models of peritoneal injury that we have recently proposed. PMID- 26676124 TI - Isolation and Propagation of Rat Peritoneal Mesothelial Cells. AB - With the development of peritoneal dialysis in many countries, there has been much interest in the cell biology of peritoneal mesothelial cells. In this chapter we describe a reliable and reproducible method for the culture of rat primary mesothelial cells (RPMCs). This chapter outlines how to isolate mesothelial cells from rat peritoneum. The subculture of primary peritoneal mesothelial cells and the characterization by immunofluorescence is also described in detail. PMID- 26676126 TI - Renal Sympathetic Denervation in Rats. AB - Experimental renal sympathetic denervation is a well-established technique. Classically, renal sympathetic denervation is achieved by dorsal rhizotomy. While more recently, direct renal sympathetic denervation is typically applied by stripping all visible renal nerve bundles followed by painting with a solution of 10 % phenol in ethanol to remove the remaining nerves. In clinical settings, a reliable marker of renal sympathetic denervation or renal sympathetic overactivity has not been established. However, in experimental models, successful renal sympathetic denervation is validated by a decrease in renal norepinephrine content levels. This facilitates the assessment of incomplete denervation by technical failure and reinnervation for long-term experimental models. In this chapter, we introduce comprehensive methods for direct renal sympathetic denervation and measurement of renal norepinephrine content levels. PMID- 26676127 TI - Decellularization of Rat Kidneys to Produce Extracellular Matrix Scaffolds. AB - The extracellular matrix (ECM) retains three-dimensional structures for the stimulation of cell growth, with components of the ECM relatively conserved between species. Interest in the use of decellularized scaffold-based strategies for organ regeneration is increasing rapidly. Decellularized scaffolds derived from animal organs are a promising material for organ engineering, with a number of prominent advances having been reported in the past few years.In this article we describe a simple and robust methodology for generating decellularized rat kidneys. To obtain these scaffolds, we perfuse rat kidneys with detergents through the abdominal aorta. After decellularization, kidney scaffolds are harvested for evaluation of vascular structure and histology. Qualitative evaluation involves vascular corrosion casting, transmission electron microscopy, and several different histological and immunofluorescent methods. SDS residue levels are assessed by ultraviolet-visible spectrophotometer (UV-VIS). PMID- 26676128 TI - Use of Cationized Ferritin Nanoparticles to Measure Renal Glomerular Microstructure with MRI. AB - Magnetic resonance imaging (MRI) is becoming important for whole-kidney assessment of glomerular morphology, both in vivo and ex vivo. MRI-based renal morphological measurements can be made in intact organs and allow direct measurements of every perfused glomerulus. Cationic ferritin (CF) is used as a superparamagnetic contrast agent for MRI. CF binds to the glomerular basement membrane after intravenous injection, allowing direct, whole-kidney measurements of glomerular number, volume, and volume distribution. Here we describe the production, testing, and use of CF as an MRI contrast agent for quantitative glomerular morphology in intact mouse, rat, and human kidneys. PMID- 26676129 TI - Biopsychronology: A Method Using Live Tissue Staining to Image Cell Function in the Kidney. AB - Methods to monitor the status of a graft prior to transplantation are highly desirable to avoid unnecessary surgical interventions and follow-up treatments and to optimize the clinical outcome as delayed graft function may lead to costly and lengthy follow-up treatments or even organ loss. As a promising step in this direction we present a method which combines the use of fine needle biopsies, the staining of living cells with dyes suitable to monitor mitochondrial status/cellular integrity, and live confocal real-time analysis.This approach provides information about the functional and structural intactness of an organ within a few minutes. To confirm the feasibility of this approach, we recently published a pilot study using rodent kidneys. The results demonstrated that this method is suitable to monitor organ damage caused by ischemia or short periods of reperfusion. This procedure required minimal time for sample preparation and data acquisition and is suitable for recording damage resulting from unphysiological stress to the organ. PMID- 26676130 TI - Prolonged and Continuous Measurement of Kidney Oxygenation in Conscious Rats. AB - A relative deficiency in kidney oxygenation, i.e., renal hypoxia, may contribute to the initiation and progression of acute and chronic kidney disease. A critical barrier to investigate this is the lack of methods allowing measurement of the partial pressure of oxygen in kidney tissue for long periods in vivo. We have developed, validated, and tested a novel telemetric method that can do this. Here we provide details on the calibration, implantation, implementation for data recording, and reuse of this telemetry-based technology for measurement of medullary tissue oxygen tension in conscious, unrestrained rats. This technique provides an important additional tool for investigating the impact of renal hypoxia in biology and pathophysiology. PMID- 26676131 TI - Magnetic Resonance Imaging (MRI) Analysis of Ischemia/Reperfusion in Experimental Acute Renal Injury. AB - Imbalance between renal oxygen delivery and demand in the first hours after reperfusion is suggested to be decisive in the pathophysiological chain of events leading to ischemia-induced acute kidney injury. Here we describe blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) for continuous monitoring of the deoxyhemoglobin-sensitive MR parameter T 2* in the renal cortex, outer medulla, and inner medulla of rats throughout renal ischemia/reperfusion (I/R). Changes during I/R are benchmarked against the effects of variations in the fraction of inspired oxygen (hypoxia, hyperoxia). This method may be useful for investigating renal blood oxygenation of rats in vivo under various experimental (patho)physiological conditions. PMID- 26676132 TI - Assessment of Renal Hemodynamics and Oxygenation by Simultaneous Magnetic Resonance Imaging (MRI) and Quantitative Invasive Physiological Measurements. AB - In vivo assessment of renal perfusion and oxygenation under (patho)physiological conditions by means of noninvasive diagnostic imaging is conceptually appealing. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and quantitative parametric mapping of the magnetic resonance (MR) relaxation times T 2* and T 2 are thought to provide surrogates of renal tissue oxygenation. The validity and efficacy of this technique for quantitative characterization of local tissue oxygenation and its changes under different functional conditions have not been systematically examined yet and remain to be established. For this purpose, the development of an integrative multimodality approaches is essential. Here we describe an integrated hybrid approach (MR-PHYSIOL) that combines established quantitative physiological measurements with T 2* (T 2) mapping and MR-based kidney size measurements. Standardized reversible (patho)physiologically relevant interventions, such as brief periods of aortic occlusion, hypoxia, and hyperoxia, are used for detailing the relation between the MR-PHYSIOL parameters, in particular between renal T 2* and tissue oxygenation. PMID- 26676133 TI - Intravital Multiphoton Imaging of the Kidney: Tubular Structure and Metabolism. AB - Multiphoton microscopy (MPM) allows the visualization of dynamic pathophysiological events in real time in live animals. Intravital imaging can be applied to investigate novel mechanisms and treatments of different forms of kidney disease as well as improve our understanding of normal kidney physiology. Using rodent models, in conjunction with endogenous fluorescence and infused exogenous fluorescent dyes, measurement can be made of renal processes such as glomerular permeability, juxtaglomerular apparatus function, interactions of the tubulointerstitium, tubulovascular interactions, vascular flow rate, and the renin-angiotensin-aldosterone system. Subcellular processes including mitochondrial dynamics, reactive oxygen species production, cytosolic ion concentrations, and death processes of apoptosis and necrosis can also be seen and measured by MPM. The current methods chapter presents an overview of MPM with a focus on techniques for intravital kidney imaging and gives examples of instances where intravital MPM has been utilized to study renal pathophysiology. Suggestions are provided for MPM methods within the confines of intravital microscopy and selected kidney structure. MPM is undoubtedly a powerful new technique for application in experimental nephrology, and we believe it will continue to create new paradigms for understanding and treating kidney disease. PMID- 26676134 TI - Vascular Calcification in Uremia: New-Age Concepts about an Old-Age Problem. AB - A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes. PMID- 26676135 TI - An In Vitro Murine Model of Vascular Smooth Muscle Cell Mineralization. AB - Vascular calcification (VC) is seen ubiquitously in aging blood vessels and prematurely in disease states like renal failure. It is thought to be driven by a number of systemic and local factors that lead to extra-osseous deposition of mineral in the vascular wall and valves as a common endpoint. The response of resident vascular smooth muscle cell to these dystrophic signals appears to be important in this process. Whilst in vivo models allow the observation of global changes in a pro-calcific environment, identifying the specific cells and mechanisms involved has been largely garnered from in vitro experiments, which provide added benefits in terms of reproducibility, cost, and convenience. Here we describe a 7-21 day cell culture model of calcification developed using immortalized murine vascular smooth muscle cells (MOVAS-1). This model provides a method by which vascular smooth muscle cell involvement and manipulation within a mineralizing domain can be studied. PMID- 26676136 TI - The Isolation and Quantitation of Fetuin-A-Containing Calciprotein Particles from Biological Fluids. AB - Multiple overlapping systemic and local inhibitory networks have evolved to prevent the unwanted deposition of mineral at ectopic sites. Fetuin-A is a liver derived glycoprotein abundant in plasma that binds and stabilizes nascent mineral ion nuclei to form soluble colloidal high molecular weight complexes, called calciprotein particles (CPP). The binding of fetuin-A to mineral retards crystal ripening and precipitation from the aqueous phase, thereby facilitating the regulated clearance of mineral debris from the extracellular fluid. However, persistent disturbances in this humoral homeostatic system, as frequently seen in patients with Chronic Kidney Disease, may lead to the accumulation and aggregation of these nanoparticles in extraosseous tissues like the vasculature, driving inflammatory cascades, aberrant tissue remodeling, and functional impairment. Consistent with this conceptual framework, higher circulating CPP levels are associated with reduced renal function, increments in systemic inflammatory markers, derangements in bone morphogenetic cytokines, higher vascular calcification scores, aortic stiffening and an increased risk of death. This chapter describes optimized sample collection and preparative procedures for the isolation and enrichment of CPP from biological fluids. Methods for CPP quantitation are critically reviewed and detailed. PMID- 26676137 TI - Combining Near Infrared Fluorescent Imaging for Calcification and Inflammation in Vascular Tissue Samples Ex Vivo. AB - Quantification of vascular lesions in models of vascular calcification is crucial for testing novel treatments, but remains a challenging endeavor. Conventional methods include Oil-Red-O staining of whole tissue samples, calcium quantification in incinerated samples, or stereoisometric histologic processing. While most techniques offer fairly high levels of reliability, all of them share the fact that samples are not available for other assays following the analysis, as tissue is altered or destroyed in the course of the procedure. Furthermore, none is capable of measuring both calcification and inflammation at the same time. Here we present a novel technique for the simultaneous quantification of vascular inflammation and calcification, after which samples are still available for further histologic processing. PMID- 26676138 TI - Laser Capture Microdissection of Archival Kidney Tissue for qRT-PCR. AB - Whole-organ molecular analysis of the kidney potentially misses important factors involved in the pathogenesis of disease in glomeruli and tubules. Organ wide analysis can however be augmented by using laser capture microdissection (LCM) to isolate morphologically similar cells and nephron structures from a heterogeneous tissue section via direct visualization of the cells. The protocol here provides a practical approach utilizing LCM in combination with RNA isolation techniques for downstream analysis. This technique is readily applicable to study mRNA expression in isolated glomeruli and tubules in both experimental animal models and human kidney biopsy material. PMID- 26676139 TI - Using Phos-Tag in Western Blotting Analysis to Evaluate Protein Phosphorylation. AB - Protein phosphorylation has traditionally been detected by radioisotope phosphate labeling of proteins with radioactive ATP. Several nonradioactive assays with phosphorylation site-specific antibodies are now available for the analysis of phosphorylation status at target sites. However, due to their high specificity, these antibodies they cannot be used to detect unidentified phosphorylation sites. Recently, Phos-tag technology has been developed to overcome the disadvantages and limitations of phosphospecific antibodies. Phos-tag and its derivatives conjugated to biotin, acrylamide, or agarose, form alkoxide-bridged dinuclear metal complexes, which can capture phosphate monoester dianions bound to serine, threonine, and tyrosine residues, in an amino acid sequence independent manner. Here, we describe our method, which is based on in vitro kinase assay and Western blotting analysis using biotinylated Phos-tag and horseradish peroxidase-conjugated streptavidin, to determine the sites of TRPC6 (transient receptor potential canonical 6) channel phosphorylated by protein kinase A. PMID- 26676140 TI - Qualitative and Quantitative Analysis of Histone Deacetylases in Kidney Tissue Sections. AB - Fluorescent microscope imaging technologies are increasing in their applications and are being used on a wide scale. However methods used to quantify the level of fluorescence intensity are often not utilized-perhaps given the result may be immediately seen, quantification of the data may not seem necessary. However there are a number of reasons given to quantify fluorescent images including the importance of removing potential bias in the data upon observation as well as quantification of large numbers of images gives statistical power to detect subtle changes in experiments. In addition discreet localization of a protein could be detected without selection bias that may not be detectable by eye. Such data will be deemed useful when detecting the levels of HDAC enzymes within cells in order to develop more effective HDAC inhibitor compounds for use against multiple diseased states. Hence, we discuss a methodology devised to analyze fluorescent images using Image J to detect the mean fluorescence intensity of the 11 metal-dependent HDAC enzymes using murine kidney tissue sections as an example. PMID- 26676141 TI - Novel trends in transrectal ultrasound imaging of prostate gland carcinoma. AB - Carcinoma of the prostate gland is the most common neoplasm in men. Its treatment depends on multiple factors among which local staging plays a significant role. The basic method is transrectal ultrasound imaging. This examination enables imaging of the prostate gland and its abnormalities, but it also allows ultrasound-guided biopsies to be conducted. A conventional gray-scale ultrasound examination enables assessment of the size, echostructure and outlines of the anatomic capsule, but in many cases, neoplastic lesions cannot be observed. For this reason, new sonographic techniques are implemented in order to facilitate detectability of cancer. The usage of contrast agents during transrectal ultrasound examination must be emphasized since, in combination with color Doppler, it facilitates detection of cancerous lesions by visualizing flow which is not observable without contrast enhancement. Elastography, in turn, is a different solution. It uses the differences in tissue elasticity between a neoplastic region and normal prostatic parenchyma that surrounds it. This technique facilitates detection of lesions irrespective of their echogenicity and thereby supplements conventional transrectal examinations. However, the size of the prostate gland and its relatively far location from the transducer may constitute limitations to the effectiveness of elastography. Moreover, the manner of conducting such an examination depends on the examiner and his or her subjective assessment. Another method, which falls within the novel, popular trend of combining imaging methods, is fusion of magnetic resonance imaging and transrectal sonography. The application of multidimensional magnetic resonance imaging, which is currently believed to be the best method for prostate cancer staging, in combination with the availability of a TRUS examination and the possibility of monitoring biopsies in real-time sonography is a promising alternative, but it is associated with higher costs and longer duration of the examination. This paper presents the most important novel trends in transrectal imaging in prostate cancer diagnosis based on the review of the articles available in the PubMed base and published after 2010. PMID- 26676142 TI - The Role of Parenting Styles in the Relation Between Functions of Aggression and Internalizing Symptoms in a Child Psychiatric Inpatient Population. AB - Psychiatric inpatient hospitalization is a costly intervention for youth. With rates of hospitalization rising, efforts to refine prevention and intervention are necessary. Aggression often precedes severe internalizing behaviors, and proactive and reactive functions of aggression are differentially associated with internalizing symptomatology. Thus, further understanding of the links between functions of aggression and internalizing symptomatology could aid in the improvement of interventions for hospitalized youth. The current study examined parenting styles, gender, and age as potential moderators of the relations between proactive and reactive aggression and internalizing symptoms. Participants included 392 children, 6-12 years of age admitted consecutively to a psychiatric inpatient unit. Reactive aggression was uniquely associated with anxiety symptoms. However, proactive aggression was associated with internalizing problems only when specific parenting styles and demographic factors were present. Although both proactive and reactive subtypes of aggression were associated with internalizing symptoms, differential associations were evident. Implications of findings are discussed. PMID- 26676143 TI - The Potential of Failure: Resulting Questions About Faculty Engagement. PMID- 26676144 TI - Male functions and malfunctions: the impact of phosphoinositides on pollen development and pollen tube growth. AB - KEY MESSAGE: Phosphoinositides in pollen. In angiosperms, sexual reproduction is a series of complex biological events that facilitate the distribution of male generative cells for double fertilization. Angiosperms have no motile gametes, and the distribution units of generative cells are pollen grains, passively mobile desiccated structures, capable of delivering genetic material to compatible flowers over long distances and in an adverse environment. The development of pollen (male gametogenesis) and the formation of a pollen tube after a pollen grain has reached a compatible flower (pollen tube growth) are important aspects of plant developmental biology. In recent years, a wealth of information has been gathered about the molecular control of cell polarity, membrane trafficking and cytoskeletal dynamics underlying these developmental processes. In particular, it has been found that regulatory membrane phospholipids, such as phosphoinositides (PIs), are critical regulatory players, controlling key steps of trafficking and polarization. Characteristic features of PIs are the inositol phosphate headgroups of the lipids, which protrude from the cytosolic surfaces of membranes, enabling specific binding and recruitment of numerous protein partners containing specific PI-binding domains. Such recruitment is globally an early event in polarization processes of eukaryotic cells and also of key importance to pollen development and tube growth. Additionally, PIs serve as precursors of other signaling factors with importance to male gametogenesis. This review highlights the recent advances about the roles of PIs in pollen development and pollen function. PMID- 26676146 TI - Baseline white matter microstructural integrity is not related to cognitive decline after 5 years: The RUN DMC study. PMID- 26676147 TI - Perinatal Considerations in Women With Previous Diagnosis of Cancer. AB - As the average age that women have their first child increases and cancer therapies improve survival, obstetricians are more likely to care for pregnant women who have survived cancer. Managing these pregnancies can be challenging, as they may be associated with higher risks of maternal and neonatal morbidity and mortality. Different types of cancer require different types of intervention, including surgery, chemotherapy, radiation, or combinations of these. Prior cancer treatments therefore present different potential complications during pregnancy. Although for most women who survive cancer carrying a pregnancy does not seem to increase mortality rates, there are some associated neonatal morbidities. The most common perinatal complication associated with pregnancy after cancer is prematurity. Women who desire pregnancy after cancer survival should not be discouraged, but appropriate counseling and follow-up should be provided. PMID- 26676148 TI - Prenatal Stress, Prematurity, and Asthma. AB - Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health. PMID- 26676149 TI - Enhanced Recovery Pathways in Gynecology and Gynecologic Oncology. AB - IMPORTANCE: Enhanced recovery programs (ERPs) are considered standard of care across a variety of surgical disciplines, but ERPs have not been widely adopted in gynecology. OBJECTIVE: The aim of this study was to describe ERP principles and the role of ERPs in gynecology and gynecologic oncology. EVIDENCE ACQUISITION: Comprehensive literature search was performed using MEDLINE, the Cochrane Collaboration Database, and PubMed. RESULTS: Meta-analyses of a substantial number of randomized controlled trials have shown that implementation of ERP protocols is associated with decreased length of hospital stay, a decrease in rates of postoperative complication, decreased morbidity, and cost savings while preserving patient satisfaction and quality of life. CONCLUSIONS AND RELEVANCE: High-quality evidence exists for improved outcomes among patients in ERPs. Enhanced recovery programs save resources and costs across the health care system. As quality metrics and bundled payments increase in health care, ERPs will have increasing prominence. PMID- 26676151 TI - Case Report: Neuropathic pain in a patient with congenital insensitivity to pain. AB - We report a unique case of a woman with Channelopathy-associated Insensitivity to Pain (CIP) Syndrome, who developed features of neuropathic pain after sustaining pelvic fractures and an epidural hematoma that impinged on the right fifth lumbar (L5) nerve root. Her pelvic injuries were sustained during painless labor, which culminated in a Cesarean section. She had been diagnosed with CIP as child, which was later confirmed when she was found to have a null mutation of the SCN9a gene that encodes the voltage-gated sodium channel Nav1.7. She now complains of troubling continuous buzzing in both legs and a vice-like squeezing in the pelvis on walking. Quantitative sensory testing showed that sensory thresholds to mechanical stimulation of the dorsum of both feet had increased more than 10-fold on both sides compared with tests performed before her pregnancy. These findings fulfill the diagnostic criteria for neuropathic pain. Notably, she only experiences the negative symptoms (such as numbness and tingling) and she has not reported sharp, burning or electric shock sensations, although the value of verbal descriptors is somewhat limited in a person who has never felt pain before. However, her case strongly suggests that at least some of the symptoms of neuropathic pain can persist despite the absence of the Nav1.7 channel. Pain is a subjective experience and this case sheds light on the transmission of neuropathic pain in humans that cannot be learned from knockout mice. PMID- 26676150 TI - Health-related quality of life in multiple sclerosis: role of cognitive appraisals of self, illness and treatment. AB - PURPOSE: Health-related quality of life (HRQoL) is considered an important measure of treatment and rehabilitation outcomes in multiple sclerosis (MS) patients. In this study, we used multivariate regression analysis to examine the role of cognitive appraisals, adjusted for clinical, socioeconomic and demographic variables, as correlates of HRQoL in MS. METHODS: The cross-sectional study included 257 MS patients, who completed Multiple Sclerosis Impact Scale, Generalized Self-Efficacy Scale, Rosenberg Self-Esteem Scale, Brief Illness Perception Questionnaire, Treatment Beliefs Scale, Actually Received Support Scale (a part of Berlin Social Support Scale) and Socioeconomic Resources Scale. Demographic and clinical characteristics of the participants were collected with a self-report survey. Correlation and regression analyses were conducted to determine associations between the variables. RESULTS: Five variables, illness identity (beta = 0.29, p <= 0.001), self-esteem (beta = -0.22, p <= 0.001), general self-efficacy (beta = -0.21, p <= 0.001), disability subgroup "EDSS" (beta = 0.14, p = 0.006) and age (beta = 0.12, p = 0.012), were significant correlates of HRQoL in MS. These variables explained 46 % of variance in the dependent variable. Moreover, we identified correlates of physical and psychological dimensions of HRQoL. CONCLUSIONS: Cognitive appraisals, such as general self-efficacy, self-esteem and illness perception, are more salient correlates of HRQoL than social support, socioeconomic resources and clinical characteristics, such as type and duration of MS. Therefore, interventions aimed at cognitive appraisals may also improve HRQoL of MS patients. PMID- 26676153 TI - Influence of Health Insurance Status on the Timing of Surgery and Treatment of Bucket-Handle Meniscus Tears. AB - BACKGROUND: Lack of insurance has been shown to lead to delays in seeking care as well as fewer preventive medicine visits and poorer overall health status. PURPOSE: To investigate the effects of insurance status on the timing and treatment of patients with bucket-handle meniscus tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Charts from 2004 to 2013 were retrospectively reviewed for patients diagnosed with bucket-handle meniscus tears. Patients were divided into 2 groups: insured or underinsured. The insured group included patients with commercial insurance or Medicare. The underinsured group included patients with Medicaid or Charity Care. Time intervals were categorized as <6 weeks or >=6 weeks. RESULTS: A total of 52 patients were included in this study: 15 (29%) insured and 37 (71%) underinsured. Underinsured patients experienced delays in initial presentation to an orthopaedic surgeon (P = .004), time from magnetic resonance imaging to surgery (P = .01), and time from injury to surgery (P = .007). Repair rates were 40% and 38% (P > .999) for the insured and underinsured, respectively. Repair rates for <6 weeks from injury to surgery were 75% for insured (P = .007) and 100% for underinsured patients (P = .001). Repair rates for >=6 weeks from injury to surgery were 0% for insured and 30% for underinsured patients. Overall, patients with an injury-to-surgery time of <6 weeks had a significantly higher repair rate (87%) than those managed >6 weeks (19%) (P < .001). CONCLUSION: Underinsured patients experience significant delays in time to presentation and overall time to surgery. However, the overall repair rate between the insured and underinsured is similar. Regardless of insurance status, patients undergoing arthroscopy within 6 weeks of injury have a significantly higher repair rate than those after 6 weeks. CLINICAL RELEVANCE: Patients undergoing arthroscopy within 6 weeks of injury have a significantly higher repair rate than those after 6 weeks. PMID- 26676152 TI - Crosstalk with cancer-associated fibroblasts induces resistance of non-small cell lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibition. AB - Although lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are highly sensitive to selective EGFR tyrosine kinase inhibitors (TKIs), these tumors invariably develop acquired drug resistance. Host stromal cells have been found to have a considerable effect on the sensitivity of cancer cells to EGFR TKIs. Little is known, however, about the signaling mechanisms through which stromal cells contribute to the response to EGFR TKI in non-small cell lung cancer. This work examined the role of hedgehog signaling in cancer associated fibroblast (CAF)-mediated resistance of lung cancer cells to the EGFR TKI erlotinib. PC9 cells, non-small cell lung cancer cells with EGFR-activating mutations, became resistant to the EGFR TKI erlotinib when cocultured in vitro with CAFs. Polymerase chain reaction and immunocytochemical assays showed that CAFs induced epithelial to mesenchymal transition phenotype in PC9 cells, with an associated change in the expression of epithelial to mesenchymal transition marker proteins including vimentin. Importantly, CAFs induce upregulation of the 7-transmembrane protein smoothened, the central signal transducer of hedgehog, suggesting that the hedgehog signaling pathway is active in CAF-mediated drug resistance. Indeed, downregulation of smoothened activity with the smoothened antagonist cyclopamine induces remodeling of the actin cytoskeleton independently of Gli-mediated transcriptional activity in PC9 cells. These findings indicate that crosstalk with CAFs plays a critical role in resistance of lung cancer to EGFR TKIs through induction of the epithelial to mesenchymal transition and may be an ideal therapeutic target in lung cancer. PMID- 26676154 TI - Unexpected photoluminescence properties from one-dimensional molecular chains. AB - Unlike bulk iodine, iodine molecular chains formed inside one dimensional (1D) nanochannels of AlPO4-5 (AFI) single crystals show unexpected PL behavior. Thanks to its unique 1D structure, the PL exhibits obvious polarization both in excitation and emission, by changing the angle between the c-axis of the channels and the polarization direction of the incident laser. As pressure increases, the PL intensity increases obviously due to the population increase of (I2)n chains upon compression. In contrast, the breaking of the (I2)n chain at high temperature leads to the decrease of PL intensity. Our theoretical calculation further points out that the PL may arise from the intrinsic band structure of (I2)n chains. PMID- 26676155 TI - A Rare Case of Pneumoureter: Emphysematous Pyelitis versus Emphysematous Pyelonephritis. AB - Emphysematous pyelitis is a rare benign entity which is defined as isolated gas production in the pelvicalyceal system, ureters or in the urinary bladder as a consequence of acute bacterial renal infection. In this case report we present a case with no prior medical history of diabetes or urinary obstruction who presented with uncontrolled hyperglycaemia for the first time associated with emphysematous pyelonephritis. Further, the imaging differences between emphysematous pyelonephritis (EPN) and emphysematous pyelitis (EP) has been discussed along with the approach and their management. PMID- 26676158 TI - Gangrenous Cystitis in A Woman Following Vaginal Delivery: An Uncommon Occurrence - A Case Report. AB - Gangrenous cystitis is now a rare condition with the advent of antibiotics and better obstetric services. It has a multifactorial causation manifesting as urosepsis or peritonitis. We report a case of 24-year-old lady who presented at day 12 postpartum with abdominal distension and vomitings. History of prolonged labour was present. Peritoneal tap was suggestive of pyoperitoneum. Hence she was taken up for emergency laparotomy and incidentally found to have bladder necrosis. Partial cystectomy was done and patient was discharged in a satisfactory condition after 2 weeks. PMID- 26676145 TI - Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy. AB - Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca(2+)-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca(2+) entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease. PMID- 26676157 TI - An Open Label Parallel Group Study to Assess the Effects of Amlodipine and Cilnidipine on Pulse Wave Velocity and Augmentation Pressures in Mild to Moderate Essential Hypertensive Patients. AB - INTRODUCTION: Hypertension is a major cardiovascular risk factor, which affects both large and small arteries. Because of the associated morbidity and mortality and the cost to society, it is an important public health challenge. Population based studies have reported that large artery stiffness is an important determinant of cardiovascular events and mortality in general population and in patients with hypertension. This study was designed to compare the effects of 8 weeks blood pressure control using Amlodepine and cilnidipine on haemodynamic parameters and vascular indices in mild to moderate hypertensive patients. MATERIALS AND METHODS: A total of 60 patients were enrolled in the study. Thirty patients were randomly allocated to either Amlodipine 5 mg OD or Cilnidipine 10 mg OD for duration of eight weeks. Blood Pressure (BP), Heart Rate (HR), carotid femoral Pulse Wave Velocity (cf PWV), Augmentation Index (AIx) and Aortic augmentation pressure (AoAP) were measured at baseline and at the end of eight weeks. RESULTS: The mean change in the central artery stiffness from baseline to week-8 in the Amlodipine group as compared to Cilnidipine group cf PWV -139.3+/ 27.7 vs. -234.1+/-74.8 cm/s p=<0.0001, AoAP -3.8+/-1.5 vs. -5.6+/-3.3 mm of Hg p=0.008 and AIx -6.8+/-2.4 vs. -10.8+/-4.4 %, p=<0.0001 respectively. CONCLUSION: This study showed that the L/N-type calcium channel antagonist Cilnidipine has a similar antihypertensive action to Amlodipine, but is superior in improving the arterial stiffness. PMID- 26676156 TI - Perceived Control Predicts Pulse Pressure in African American Men: The Baltimore Study of Black Aging. AB - OBJECTIVE: Poorer health profiles among African American men throughout the life course evince greater rates of cardiovascular disease (CVD) and significantly earlier mortality compared with other groups. Despite growing emphasis on identifying how psychosocial factors influence disparate disease risk, little of this research has focused intently on African American men. METHODOLOGY: Using hierarchical linear regression, we explored the additive influence of stress, depression, and perceived control on pulse pressure, an established marker of CVD risk, in a sample (N = 153) of African American men (mean age = 66.73 +/- 9.29) from the Baltimore Study of Black Aging (BSBA). RESULTS: After accounting for age and health status indicators, perceived control emerged as a significant predictor of pulse pressure. DISCUSSION: These findings suggest that greater belief in one's own efficacy is a protective factor for cardiovascular health among African American men. Future research should examine whether enhancing perceived control can have an appreciable impact on the immense CVD burden in this and other at-risk populations. PMID- 26676159 TI - Correlation of coronary plaque characteristics and obstructive stenosis with chronic kidney disease by coronary CT angiography. AB - BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events. We evaluated the correlation of coronary plaque characteristics and obstructive stenosis with CKD by coronary computed tomographic angiography (CCTA). METHODS: We enrolled 491 subjects who were suspected coronary artery disease (CAD) undergoing CCTA. Estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD) equation. Patients were subdivided into four groups based on their eGFR: normal GFR (n=213, eGFR >=90 mL/min/1.73 m(2)), mild renal insufficiency (n=191, eGFR 60-89 mL/min/1.73 m(2)), moderate renal insufficiency(n=78, eGFR <60 mL/min/1.73 m(2), >=30 mL/min/1.73 m(2)), and severe renal insufficiency (n=9, eGFR <30 mL/min/1.73 m(2), >=15 mL/min/1.73 m(2)). RESULTS: Spearman correlation regression analysis showed that the prevalence of any plaque, calcified plaque (CP), mixed plaque (MP) were positively correlate with CKD (r=0.173, P<0.001; r=0.127, P=0.005; r=0.171, P<0.001), after adjustment for traditional risk factors the prevalence of any plaque and MP were still positively correlate with CKD (r=0.106, P=002; r=0.178, P<0.001). And the prevalence of any stenosis and severe stenosis were positively correlate with CKD (r=0.13, P<0.001; r=0.149, P<0.001), after adjustment for traditional risk factors were still positively correlate with CKD (r=0.134, P=0.003; r=0.174, P<0.001). CONCLUSIONS: CKD is closely related with occurrence of CAD. CKD patients from mild renal insufficiency to severe renal insufficiency are the risk factors for CAD. More serious renal function impairment will indicates higher risk of coronary plaque, MP and obstructive stenosis. PMID- 26676161 TI - Differential pharmacology and clinical utility of long-acting bronchodilators in COPD - focus on olodaterol. AB - Olodaterol (BI 1744 CL) is a novel, once-daily long-acting beta2-agonist (LABA) designed with the aim of improving beta2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 MUg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy. PMID- 26676162 TI - T-DM1 Extends Survival in HER2+ Breast Cancer. AB - Results from the phase III TH3RESA study show that T-DM1 is effective in patients with metastatic HER2-positive breast cancer that has progressed despite two or more HER2-targeted therapies, extending their median overall survival by nearly 7 months. PMID- 26676160 TI - Hepatitis B Virus-Related Hepatocellular Carcinoma: Pathogenic Mechanisms and Novel Therapeutic Interventions. AB - BACKGROUND: Infection with the hepatitis B virus (HBV) is one of most important risk factors for hepatocellular carcinoma (HCC). Indeed, HBV is considered a group 1 human carcinogen and is a highly oncogenic agent. HBV cannot be effectively controlled or completely eliminated, so chronic HBV infection is a public health challenge worldwide. SUMMARY: It is now believed that HBV-induced HCC involves a complex interaction between multiple viral and host factors. Many factors contribute to HBV-associated HCC, including products of HBV, viral integration and mutation, and host susceptibility. This review outlines the main pathogenic mechanisms with a focus on those that suggest novel targets for the prevention and treatment of HCC. KEY MESSAGE: HBV infection is an important risk factor for HCC. Understanding the interaction between viral and host factors in HBV-induced HCC will reveal potential targets for future therapies. PRACTICAL IMPLICATIONS: The two main therapeutic strategies consist of antiviral agents and immunotherapy-based approaches. Dendritic cell-based immunotherapy is promising for restoring the T cell-mediated antiviral immune response. Another approach is the specific expansion of the host's pool of HBV-specific T cells. Stimulation of the Toll-like receptors (TLRs), particularly TLR9, provides another means of boosting the antiviral response. Combination therapy with cytokines (interferon gamma and tumor necrosis factor alpha) plus lamivudine is more effective than these agents used alone. Therapeutic vaccines are being developed as an alternative to long-term antiviral treatment or as an adjunct. PMID- 26676163 TI - Duration of Ebola virus RNA persistence in semen of survivors: population-level estimates and projections. AB - Ebola virus can persist in semen after recovery, potentially for months, which may impact the duration of enhanced surveillance required after interruption of transmission. We combined recent data on viral RNA persistence with weekly disease incidence to estimate the current number of semen-positive men in affected West African countries. We find the number is low, and since few reported sexual transmission events have occurred, the future risk is also likely low, although sexual health promotion remains critical. PMID- 26676164 TI - Ultrasound quiz 1. PMID- 26676165 TI - Sense of Coherence as a Predictor of Quality of Life Among Iranian Students Living in Ahvaz. AB - OBJECTIVES: There is evidence to support the correlation between a stronger sense of coherence (SOC) and better perceived quality of life (QOL). However, this association has not been described among Iranian students. METHODS: Students were selected by stratified randomization and demographic data including age, gender, and employment status were collected. SOC was measured using the short-form of the Sense of Coherence Scale (SOC-13). The World Health Organization Quality of Life (WHOQOL)-BREF questionnaire was used to assess the QOL. Data was collected over one year between 2014 and 2015. RESULTS: A total of 459 students participated in the study. The Cronbach's alpha score in domains of physical health, psychological health, environmental health, social relationships, and WHOQOL-BREF total score were 0.84, 0.83, 0.84, 0.78, and 0.94, respectively. Measured Cronbach's alpha for domains of meaningfulness, manageability, comprehensibility, and SOC-13 total score were 0.68, 0.67, 0.76, and 0.87, respectively. Marital status was not related to SOC whereas married students had significantly higher scores of QOL in the domains of psychological health, social relationships, and environment health (p=0.006, p<0.0001 and p=0.043, respectively). There were significant strong positive relationships between all components of SOC (meaningfulness, manageability, and comprehensibility) and all domains of WHOQOF-BREF (p<0.0001 for all). CONCLUSION: This study shows that SOC and marital status are significant predictors of QOL among Iranian students. PMID- 26676167 TI - Standards of the Polish Ultrasound Society - update. Ultrasound examination of thyroid gland and ultrasound-guided thyroid biopsy. AB - Ultrasonography is a primary imaging technique in patients with suspected thyroid disease. It allows to assess the location, size and echostructures of the thyroid gland as well as detect focal lesions, along with indication of their size, echogenicity, echostructure and vascularity. Based on these features, ultrasound examination allows to predict abnormal focal lesions for biopsy and monitor the biopsy needle track. This paper presents the standards of thyroid ultrasound examination regarding ultrasound apparatus technical requirements, scanning techniques, readings, measurements, and the description of the examination. It discusses the ultrasound features of increased malignancy risk in focal lesions (nodules) found in the thyroid gland. It presents indications for fine needle aspiration biopsy of the thyroid gland for the visibility of single nodules (focal lesions) and numerous lesions as well as discusses contraindications for thyroid biopsy. It describes the biopsy technique, possible complications and rules for post-biopsy monitoring of benign lesions. The paper is an update of the Standards of the Polish Ultrasound Society issued in 2011. It has been prepared on the basis of current literature, taking into account the information contained in the following publications: Thyroid ultrasound examination and Recommendations of the Polish Ultrasound Society for the performance of the FNAB of the thyroid. PMID- 26676168 TI - Rapid screening for sarcopenia. PMID- 26676170 TI - Standards of the Polish Ultrasound Society - update. Ultrasound examination of the visceral arteries. AB - Ultrasound examination is a valuable method in diagnosing visceral vasoconstriction of atherosclerotic origin, as well as constriction related to the compression of the celiac trunk. Given the standard stenosis recognition criteria of >70%, the increase in peak systolic velocity (PSV) over 200 cm/s in the celiac trunk; of PSV > 275 cm/s in the superior mesenteric artery, and of PSV > 250 cm/s in the inferior mesenteric artery, the likelihood of correct diagnosis is above 90%. In the case of stenosis due to compression of the celiac trunk by median arcuate ligament of the diaphragm, a valuable addition to the regular examination procedure is to normalize the flow velocity in the vessel, i.e. the reduction in peak systolic velocity levels below 200 cm/s, and in end-diastolic velocity (EDV) levels below 55 cm/s during deep inspiration. In the case of celiac trunk stenosis exceeding 70-80%, additional information on the level of collateral circulation can be obtained by measuring the flow in the hepatic and splenic arteries - assessing the flow velocity, resistance, and pulsatility indices (which fall below 0.65 and below 1.0 in cases of stenosis of the celiac trunk with a reduced capacity of collateral circulation), as well as assessing the changes in these parameters during normal respiration and during inspiration. This paper discusses in detail the examination methods for the celiac trunk and mesenteric arteries, as well as additional procedures used to confirm the diagnosis and pathologies affecting visceral blood flow velocity, i.e.: cirrhosis and hypersplenism. The publication is an update of the Polish Ultrasound Society guidelines published in 2011. PMID- 26676166 TI - The fate of chemoresistance in triple negative breast cancer (TNBC). AB - BACKGROUND: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol(r)). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. SCOPE OF REVIEW: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. MAJOR CONCLUSIONS: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. GENERAL SIGNIFICANCE: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy. PMID- 26676169 TI - Heat Shock Proteins: A Review of the Molecular Chaperones for Plant Immunity. AB - As sessile organisms, plants are exposed to persistently changing stresses and have to be able to interpret and respond to them. The stresses, drought, salinity, chemicals, cold and hot temperatures, and various pathogen attacks have interconnected effects on plants, resulting in the disruption of protein homeostasis. Maintenance of proteins in their functional native conformations and preventing aggregation of non-native proteins are important for cell survival under stress. Heat shock proteins (HSPs) functioning as molecular chaperones are the key components responsible for protein folding, assembly, translocation, and degradation under stress conditions and in many normal cellular processes. Plants respond to pathogen invasion using two different innate immune responses mediated by pattern recognition receptors (PRRs) or resistance (R) proteins. HSPs play an indispensable role as molecular chaperones in the quality control of plasma membrane-resident PRRs and intracellular R proteins against potential invaders. Here, we specifically discuss the functional involvement of cytosolic and endoplasmic reticulum (ER) HSPs/chaperones in plant immunity to obtain an integrated understanding of the immune responses in plant cells. PMID- 26676171 TI - SUSTAINED ISOMETRIC SHOULDER CONTRACTION ON MUSCULAR STRENGTH AND ENDURANCE: A RANDOMIZED CLINICAL TRIAL. AB - BACKGROUND: The Advanced Throwers Ten Exercise Program incorporates sustained isometric contractions in conjunction with dynamic shoulder movements. It has been suggested that incorporating isometric holds may facilitate greater increases in muscular strength and endurance. However, no objective evidence currently exists to support this claim. HYPOTHESIS/PURPOSE: The purpose of this research was to compare the effects of a sustained muscle contraction resistive training program (Advanced Throwers Ten Program) to a more traditional exercise training protocol to determine if increases in shoulder muscular strength and endurance occur in an otherwise healthy population. It was hypothesized that utilizing a sustained isometric hold during a shoulder scaption exercise from the Advanced Throwers Ten would produce greater increases in shoulder strength and endurance as compared to a traditional training program incorporating a isotonic scapular plane abduction (scaption) exercise. STUDY DESIGN: Randomized Clinical Trial. METHOD: Fifty healthy participants were enrolled in this study, of which 25 were randomized into the traditional training group (age: 26 +/- 8, height:172 +/- 10 cm, weight: 73 +/- 13 kg, Marx Activity Scale: 11 +/- 4) and 25 were randomized to the Advanced Throwers Ten group (age: 28 +/- 9, height: 169 +/- 23 cm, weight: 74 +/- 16 kg, Marx Activity Scale: 11 +/- 5). No pre-intervention differences existed between the groups (P>0.05). Arm endurance and strength data were collected pre and post intervention using a portable load cell (BTE Evaluator, Hanover, MD). Both within and between group analyses were done in order to investigate average torque (strength) and angular impulse (endurance) changes. RESULTS: The traditional and Advanced Throwers Ten groups both significantly improved torque and angular impulse on both the dominant and non dominant arms by 10-14%. There were no differences in strength or endurance following the interventions between the two training groups (p>0.75). CONCLUSIONS: Both training approaches increased strength and endurance as the muscle loads were consistent between protocols indicating that either approach will have positive effects. LEVEL OF EVIDENCE: Level 2. PMID- 26676172 TI - Skeletal muscle microvascular function in girls with Turner syndrome. AB - BACKGROUND: Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC. METHODS: Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function. RESULTS: Participants were 13.7 +/- 3.1 years old and weighed 47.9 +/- 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups. CONCLUSIONS: Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired. GENERAL SIGNIFICANCE: This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated. PMID- 26676173 TI - Thrombosis of the persistent median artery as a cause of carpal tunnel syndrome - case study. AB - Carpal tunnel syndrome is the most frequent neuropathy of the upper extremity, that mainly occurs in manual workers and individuals, whose wrist is overloaded by performing repetitive precise tasks. In the past it was common among of typists, seamstresses and mechanics, but nowadays it is often caused by long hours of computer keyboard use. The patient usually complains of pain, hypersensitivity and paresthesia of his hand and fingers in the median nerve distribution. The symptoms often increase at night. In further course of the disease atrophy of thenar muscles is observed. In the past the diagnosis was usually confirmed in nerve conduction studies. Nowadays a magnetic resonance scan or an ultrasound scan can be used to differentiate the cause of the symptoms. The carpal tunnel syndrome is usually caused by compression of the median nerve passing under the flexor retinaculum due to the presence of structures reducing carpal tunnel area, such as an effusion in the flexor tendons sheaths (due to overload or in the course of rheumatoid diseases), bony anomalies, muscle and tendon variants, ganglion cysts or tumors. In some cases diseases of upper extremity vessels including abnormalities of the persistent median artery may also result in carpal tunnel syndrome. We present a case of symptomatic carpal tunnel syndrome caused by thrombosis of the persistent median artery which was diagnosed in ultrasound examination. The ultrasound scan enabled for differential diagnosis and resulted in an immediate referral to clinician, who recommended instant commencement on anticoagulant treatment. The follow-up observation revealed nearly complete remission of clinical symptoms and partial recanalization of the persistent median artery. PMID- 26676174 TI - Dependence of Guaiacol Peroxidase Activity and Lipid Peroxidation Rate in Drooping Birch (Betula pendula Roth) and Tillet (Tilia cordata Mill) Leaf on Motor Traffic Pollution Intensity. AB - Hormesis and paradoxical effects are frequently found for different plant parameters. These phenomena were also observed for lipid peroxidation (LP) rate at environmental pollution. However, the role of antioxidant enzymes, particularly guaiacol peroxidases (GPX), in a nonmonotonic variation in the LP rate remains insufficiently explored. Therefore, dependence of GPX activity and LP rate in Betula pendula and Tilia cordata leaf on motor traffic pollution intensity was studied. Regression analysis revealed dependences of LP rate and GPX activity on traffic intensity. In B pendula, GPX activity enhanced significantly (up to 2.8 times relatively control) under increased traffic that induced biphasic paradoxical effect for LP rate. In the first phase, LP level increased in comparison with the control, and in the second phase, it was normalized by enhanced GPX activity. In T cordata, dependences of GPX activity and LP rate on traffic pollution were paradoxical effects. However, there was no connection between change of GPX activity and LP rate under middle- and high level pollution: LP level reduced relatively the control or normalized even if GPX activity was lower than the control. This indicates that in T cordata, other regulatory mechanisms instead of GPX were activated which could control LP rate under middle- and high-level pollution. PMID- 26676175 TI - Serum Chromium Levels in Type 2 Diabetic Patients and Its Association with Glycaemic Control. AB - INTRODUCTION: Chromium is an essential micronutrient which is required for the normal functioning of insulin and regulation of blood sugar levels. It acts as a vital antioxidant for maintaining insulin homeostasis. In diabetes mellitus, the free radical production is increased and levels of antioxidants like chromium, vanadium, selenium and manganese are reduced. There have been previous studies to suggest that low serum levels of chromium are associated with poorer glycaemic control. AIM: To study the level of serum chromium in newly diagnosed patients with type 2 diabetes mellitus and its association with glycaemic control. MATERIALS AND METHODS: Serum chromium concentration was determined by using inductively coupled Plasma - Optical Emission Spectophotometry in 42 newly diagnosed type 2 diabetes mellitus patients without any pre-existing complications. They were divided into 2 groups - well controlled (HbA1c <=7.0%) and uncontrolled groups (HbA1c >7.0%). RESULTS: Mean serum chromium concentration measured in uncontrolled type 2 diabetic patients was significantly lower (0.065 +/- 0.03 mcg/L vs 0.103 +/- 0.04 mcg/L, p< 0.05). There was a statistically significant inverse linear correlation of the HbA1c values and the serum chromium concentration (r= -0.6514, p < 0.0001). There was also a decrease in chromium levels across both the groups with advancing age and the decrease being significant beyond 40 years of age (p<0.05). CONCLUSION: The results of our study describes the relationship between serum chromium levels and control of type 2 diabetes mellitus. Significant reduction in chromium levels are probable indicators of metabolic response to oxidative stress in patients with type 2 diabetes mellitus. Further large scale studies relating serum chromium and type 2 diabetes mellitus may help to understand more about the exact relationship. PMID- 26676176 TI - Instantaneous Decrease in Left Ventricular Afterload during Transcatheter Aortic Valve Implantation Results in Immediate Changes in Left Ventricular Strain. AB - Severe aortic stenosis causes chronic increased afterload on the left ventricle (LV) resulting in myocardial hypertrophy and ultimately dysfunction if left untreated. Transcatheter aortic valve implantation (TAVI) immediately decreases the afterload on the LV by reducing the pressure gradient through the aortic valve. In our study, we aim to evaluate immediate changes in LV mechanics using intra-procedural transesophageal echocardiography (TEE) to assess circumferential and radial strain via speckle tracking. Intra-operative TEE was performed during TAVI for 53 patients (mean age 84 +/- 8 years). Two-dimensional images in the transgastric view were acquired at the level of the papillary muscle. Circumferential and radial strain was calculated using speckle tracking with Philips Qlab software. Global LV afterload was measured by calculating valvulo arterial impedance (Zva). Immediately post-TAVI, there was a change in both radial strain rate (Pre: 0.73 +/- 0.04 vs. Post: 0.88 +/- 0.04 per second, P < 0.001) and circumferential strain rate (-0.53 +/- 0.04 (pre) vs. -0.74 +/- 0.04 (post) per second, P < 0.001). There was also an immediate improvement in circumferential global strain parameters (-14.5 +/- 5% (pre) vs. -16.0 +/- 4.7% (post), P < 0.05), whereas there was no significant change seen in global radial strain (15.6 +/- 0.8% (pre) vs. 15.2 +/- 0.9% (post), P = 0.69). No significant change was seen in LV ejection fraction (51.5 +/- 14.2% (pre) vs. 52.1 +/- 14.0% (post), P = 0.77). Speckle tracking using TEE images is feasible and identifies significant improvements in LV strain and strain rate immediately following TAVI that is not detected by conventional measure of LV function. PMID- 26676178 TI - Editorial. PMID- 26676179 TI - In memoriam: Edmund J. Fantino . PMID- 26676180 TI - The recurrence of negatively reinforced responding of humans. AB - The recurrence of negatively reinforced responding of humans was studied in three experiments. In each experiment during Baseline, key-pressing produced 3-s timeouts from a requirement to exert finger pressure on a force cell according to variable- or fixed-ratio schedules of reinforcement. In Experiment 1, resurgence was studied by arranging a differential-reinforcement-of-other-behavior schedule in the second phase, and extinction in the Test phase. In Experiment 2, ABA renewal was studied by extinguishing responding in the second phase in a different context and, in the Test phase, by presenting the Baseline-phase context when extinction still was in effect. In Experiment 3, reinstatement was studied by arranging extinction in the second phase, followed by the delivery of response-independent timeouts in the Test phase. Resurgence and renewal occurred consistently for each participant in Experiments 1 and 2, respectively. In Experiment 3, reinstatement was observed less consistently in four participants. The results of these experiments replicate and extend to negatively reinforced responding previous findings of the resurgence and renewal of positively reinforced responding obtained mainly with nonhuman animals. PMID- 26676181 TI - Intraverbal naming and equivalence class formation in children. AB - Six typically developing children between 5 and 7 years of age underwent match-to sample training to establish three-member equivalence classes after first acquiring a unique name for each stimulus. Horne and Lowe's (1996) naming hypothesis predicts that under those circumstances, match-to-sample training contingencies may establish intraverbal relations between the unique names, which in turn guide correct responses on a subsequent test for stimulus equivalence. Following training of baseline relations (AB and AC), participants received an equivalence test followed by an intraverbal test. Performance on the two tests co varied, such that three participants passed both tests, and three participants failed repeated administrations of both tests, including a modified version of the equivalence test designed to promote intraverbal responding. The participants who failed the equivalence test, however, did so primarily due to poor performance in transitivity trials, but performed accurately in symmetry trials. After training of a third relation (BC), all three participants performed accurately in a symmetry test for the remaining untrained relations (BA, CA, and CB); two of them in the absence of relevant intraverbal repertoires. PMID- 26676182 TI - When good pigeons make bad decisions: Choice with probabilistic delays and outcomes. AB - Pigeons chose between an (optimal) alternative that sometimes provided food after a 10-s delay and other times after a 40-s delay and another (suboptimal) alternative that sometimes provided food after 10 s but other times no food after 40 s. When outcomes were not signaled during the delays, pigeons strongly preferred the optimal alternative. When outcomes were signaled, choices of the suboptimal alternative increased and most pigeons preferred the alternative that provided no food after the long delay despite the cost in terms of obtained food. The pattern of results was similar whether the short delays occurred on 25% or 50% of the trials. Shortening the 40-s delay to food sharply reduced suboptimal choices, but shortening the delay to no food had little effect. The results suggest that a signaled delay to no food does not punish responding in probabilistic choice procedures. The findings are discussed in terms of conditioned reinforcement by signals for good news. PMID- 26676183 TI - Pigeons' demand and preference for specific and generalized conditioned reinforcers in a token economy. AB - Pigeons' demand and preference for specific and generalized tokens was examined in a token economy. Pigeons could produce and exchange different colored tokens for food, for water, or for food or water. Token production was measured across three phases, which examined: (1) across-session price increases (typical demand curve method); (2) within-session price increases (progressive-ratio, PR, schedule); and (3) concurrent pairwise choices between the token types. Exponential demand curves were fitted to the response data and accounted for over 90% total variance. Demand curve parameter values, Pmax , Omax and alpha showed that demand was ordered in the following way: food tokens, generalized tokens, water tokens, both in Phase 1 and in Phase 3. This suggests that the preferences were predictable on the basis of elasticity and response output from the demand analysis. Pmax and Omax values failed to consistently predict breakpoints and peak response rates in the PR schedules in Phase 2, however, suggesting limits on a unitary conception of reinforcer efficacy. The patterns of generalized token production and exchange in Phase 3 suggest that the generalized tokens served as substitutes for the specific food and water tokens. Taken together, the present findings demonstrate the utility of behavioral economic concepts in the analysis of generalized reinforcement. PMID- 26676184 TI - Perihepatic lymphadenopathy in children with chronic viral hepatitis. AB - OBJECTIVE: To assess whether lymph node enlargement in the hepatoduodenal ligament occurs in children with chronic viral hepatitis B and C in comparison to healthy controls. SUBJECT AND METHODS: In 49 patients with chronic viral hepatitis (38 with chronic hepatitis B, 11 with chronic hepatitis C, 31 male, 18 female; age range 1 to 17 years), and in 51 healthy controls (25 male, 26 female; age range 4 to 16 years), the total perihepatic lymph node volume was assessed using transabdominal ultrasonography as previously described in adult patients. RESULTS: Adequate visualization of the liver hilum was achieved in 46/49 (94%) pediatric patients with chronic viral hepatitis and in 46/51 (90%) pediatric healthy controls. In patients with adequate liver hilum visualization, enlarged perihepatic lymph nodes (longitudinal diameter >14 mm) were detected in 32/46 (70%) patients with chronic viral hepatitis and in 5/46 (11%) healthy controls. The total perihepatic lymph nodes volume [mean +/- SD] was 1.0 +/- 1.2 mL (0.1 5.4 mL) in patients with chronic viral hepatitis and 0.1 +/- 0.1 mL (0.0-0.4 mL) in healthy controls (p < 0.05). A maximal lymph node diameter >14 mm identified patients with chronic viral hepatitis with 70% sensitivity and 89% specificity. CONCLUSION: Transabdominal ultrasound can detect lymph nodes within the hepatoduodenal ligament not only in adults but also in children. Paediatric patients with chronic viral hepatitis have significantly enlarged perihepatic lymph nodes compared to controls. Therefore, sonographic assessment of perihepatic lymphadenopathy might be a non-invasive diagnostic tool to screen paediatric patients for chronic viral hepatitis. PMID- 26676185 TI - Diabetes in Sub-Saharan Africa: Distribution Based on Social Status in Libreville (Gabon). AB - OBJECTIVE: Many researchers continue to believe that urbanization is a major contributor to diabetes. We seek to demonstrate that the social status associated with urbanization has an impact on the prevalence of diabetes in Libreville, Gabon in sub-Saharan Africa. METHODS: Our study was conducted in Libreville, the capital of Gabon; the city has a population of 397,000. Our study analyzed data from the registries of patients hospitalized in 2013 in the main diabetes center in Libreville. RESULTS: The results revealed that, for 2013, 798 patients were hospitalized with diabetes at a prevalence of .2%. We found differences (P<.05) between women (423) and men (375). Mean age for women was 52.02 years and 48.88 years for men. The number of existing cases hospitalized was significantly more than new cases. All levels of society were represented in our study: students (42); military (36); administratives (99); technicians (180); unemployed (295); and retired (146). The results showed that the unemployed (36%), particularly women (29.40%) are most affected by diabetes. CONCLUSIONS: Our results show the impact of social status on the increase of diabetes in Libreville. We found that urbanization, associated with insecurity especially in women, had an effect on the prevalence of diabetes in Libreville. These results indicate that, apart from the non-modifiable factors (age, race, ethnicity), insecurity is a modifiable factor that should be taken into account. PMID- 26676186 TI - Manipulation under Anesthesia for Stiffness after Total Knee Arthroplasty. AB - PURPOSE: This study evaluated the incidence of manipulation under anesthesia (MUA) for stiffness after total knee arthroplasty (TKA) and the degree of joint motion recovery after MUA. MATERIALS AND METHODS: A total of 4,449 TKAs (2,973 patients) were performed between March 2000 and August 2014. Cases that underwent MUA for stiffness after TKA were reviewed. TKAs were performed using the conventional procedure in 329 cases and using the minimally invasive procedure in 4,120 cases. The preoperative range of joint motion, timing of manipulation, diagnosis and the range of joint motion before and after MUA were retrospectively investigated. RESULTS: MUA was carried out in 22 cases (16 patients), resulting in the incidence of 0.5%. The incidence after the conventional procedure was 1.2% and 0.4% after the minimally invasive procedure. In the manipulated knees, the preoperative range of motion (ROM) was 102.5 degrees +/-26.7 degrees , and the preoperative diagnosis was osteoarthritis in 19 cases, rheumatoid arthritis in two, and infection sequela in one. MUA was performed 4.7+/-3.0 weeks after TKA. The average ROM was 64.5 degrees +/-13.5 degrees before manipulation. At an average of 64.3+/-41.3 months after manipulation, the ROM was recovered to 113.4 degrees +/-31.2 degrees , which was an additional 49.9 degrees improvement in flexion. CONCLUSIONS: The satisfactory recovery of joint movement was achieved when MUA for stiffness was performed relatively early after TKA. PMID- 26676188 TI - Effect of grinding and heat treatment on the mechanical behavior of zirconia ceramic. AB - The present study investigated the effect of grinding on roughness, flexural strength, and reliability of a zirconia ceramic before and after heat treatment. Seven groups were tested (n = 15): a control group (labeled CG, untreated), and six groups of samples ground with diamond discs, simulating diamond burs, with grits of 200 um (G80); 160 um (G120), and 25 um (G600), either untreated or heat treated at 1200 degrees C for 2 h (labeled A). Yttria tetragonal zirconia polycrystal discs were manufactured, ground, and submitted to roughness and crystalline phase analyses before the biaxial flexural strength test. There was no correlation between roughness (Ra and Rz) and flexural strength. The reliability of the materials was not affected by grinding or heat treatment, but the characteristic strength was higher after abrasion with diamond discs, irrespective of grit size. The X-ray diffraction data showed that grinding leads to a higher monoclinic (m) phase content, whereas heat treatment produces reverse transformation, leading to a fraction of m-phase in ground samples similar to that observed in the control group. However, after heat treatment, only the G80A samples presented strength similar to that of the control group, while the other groups showed higher strength values. When zirconia pieces must be adjusted for clinical use, a smoother surface can be obtained by employing finer-grit diamond burs. Moreover, when the amount of monoclinic phase is related to the degradation of zirconia, the laboratory heat treatment of ground pieces is indicated for the reverse transformation of zirconia crystals. PMID- 26676187 TI - Up-regulation of microRNA-210 inhibits proliferation of hepatocellular carcinoma cells by targeting YES1. AB - AIM: To determine the expression of microRNA-210 (miR-210) in hepatocellular carcinoma (HCC) and to examine its role using HCC cells. METHODS: The expression of miR-210 was determined in 21 pairs of HCC samples and the corresponding surrounding non-tumor tissues. The effects of miR-210 on proliferation and cell cycle progression were examined using HepG2 and HuH7 cells. Over-expression and inhibition of miR-210 was achieved by transfection of the cells with miR-210 mimic or inhibitor. Luciferase reporter constructs were used to identify the miR 210 interacting site on Yes1. Yes1 expression was examined after miR-210 transfection, as well as in the HCC samples. RESULTS: miR-210 was significantly up-regulated by 3.4 fold (P < 0.01) in the tumor samples. The over-expression of miR-210 significantly reduced cell proliferation compared to the mock-treated cells (68.9% +/- 7.4% and 53.6% +/- 5.0%, P < 0.05 for the HepG2 and HuH7 cells respectively). Analysis of the HuH7 cells transfected with miR-210 mimic by flow cytometry showed that the cells took a longer time to reach the G2/M phase. The interaction between miR-210 and the 3'UTR of the Yes1 transcript was confirmed using a luciferase reporter assay. Over-expression of miR-210 reduced the expression of Yes1 protein in both HuH7 and HepG2 cells. Tumors with a greater than four-fold increase in the expression of miR-210 showed consistently lower expressions of Yes1 in the tumors. In nocodazole-treated cells with a significant G2/M cell population, Yes1 protein was significantly reduced and pre-inhibition of miR-210 in HuH7 cells was able to prevent the reduction of Yes1 protein expression. Knock-down of Yes1 by siRNA also led to reduced cell proliferation (70.8% +/- 7.5%, P < 0.05 in the HuH7 cells). CONCLUSION: Up-regulation of miR 210 inhibits cell proliferation. Yes1 is a target of miR-210 and affects cell proliferation in HCC. PMID- 26676189 TI - Do pediatric medicines induce topographic changes in dental enamel? AB - The purpose of the present study was to evaluate the effect of common pediatric liquid medicines on surface roughness and tooth structure loss and to evaluate the pH values of these medicines at room and cold temperatures in vitro. Eighty four bovine enamel blocks were divided into seven groups (n = 12): G1-Alivium(r), G2-Novalgina(r), G3-Betamox(r), G4-Clavulin(r), G5-Claritin(r), G6-Polaramine(r) and G7-Milli-Q water (negative control). The pH was determined and the samples were immersed in each treatment 3x/day for 5 min. 3D non-contact profilometry was used to determine surface roughness (linear Ra, volumetric Sa) and the Gap formed between treated and control areas in each block. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were also performed. The majority of liquid medicines had pH <= 5.50. G1, G4, and G5 showed alterations in Ra when compared with G7 (p < 0.05). According to Sa and Gap results, only G5 was different from G7 (p < 0.05). Alteration in surface was more evident in G5 SEM images. EDS revealed high concentrations of carbon, oxygen, phosphorus, and calcium in all tested groups. Despite the low pH values of all evaluated medicines, only Alivium(r), Clavulin(r), and Claritin(r) increased linear surface roughness, and only Claritin(r) demonstrated the in vitro capacity to produce significant tooth structure loss. PMID- 26676190 TI - Influence of crosshead speed on failure load and failure mode of restored maxillary premolars. AB - We analyzed the effect of the crosshead speed of an applied load on failure load and failure mode of restored human premolars. Fifty intact, noncarious human premolars were selected. Class II mesio-occlusodistal preparations were made with a water-cooled high-speed preparation machine, and the teeth were restored with composite resin. The specimens were divided into five groups (n = 10 each) and tested individually in a mechanical testing machine, in which a 6.0-mm-diameter steel cylinder was mounted to vary the crosshead speed: v0.5: 0.5 mm/min; v1: 1.0 mm/min; v2.5: 2.5 mm/min; v5: 5.0 mm/min; and v10: 10.0 mm/min. The cylinder contacted the facial and lingual ridges beyond the margins of the restorations. Peak load to fracture was measured for each specimen (N). The means were calculated and analyzed with one-way analysis of variance followed by Tukey's test (a = 0.05). The mean load at failure values were (N) as follows: v0.5, 769.4 +/- 174.8; v1, 645.2 +/- 115.7; v5, 614.3 +/- 126.0; v2.5, 609.2 +/- 208.1; and v10, 432.5 +/- 136.9. The fracture modes were recorded on the basis of the degree of the tooth structural and restorative damage: (I) fracture of the restoration involving a small portion of the tooth; (II) fractures involving the coronal portion of the tooth with cohesive failure of the composite resin; (III) oblique tooth and restoration fracture with periodontal involvement; and (IV) vertical root and coronal fracture. Varying crosshead speeds of 0.5-5.0 mm/min did not influence the failure load of restored maxillary premolars; however, increasing the crosshead speed to 10 mm/min decreased the failure load values and the degree of tooth structural damage. PMID- 26676192 TI - Effect of high energy X-ray irradiation on the nano-mechanical properties of human enamel and dentine. AB - Radiotherapy for malignancies in the head and neck can cause common complications that can result in tooth damage that are also known as radiation caries. The aim of this study was to examine damage to the surface topography and calculate changes in friction behavior and the nano-mechanical properties (elastic modulus, nanohardness and friction coefficient) of enamel and dentine from extracted human third molars caused by exposure to radiation. Enamel and dentine samples from 50 human third molars were randomly assigned to four test groups or a control group. The test groups were exposed to high energy X-rays at 2 Gy/day, 5 days/week for 5 days (10 Gy group), 15 days (30 Gy group), 25 days (50 Gy group), 35 days (70 Gy group); the control group was not exposed. The nanohardness, elastic modulus, and friction coefficient were analyzed using a Hysitron Triboindenter. The nano mechanical properties of both enamel and dentine showed significant dose-response relationships. The nanohardness and elastic modulus were most variable between 30 50 Gy, while the friction coefficient was most variable between 0-10 Gy for dentine and 30-50 Gy for enamel. After exposure to X-rays, the fracture resistance of the teeth clearly decreased (rapidly increasing friction coefficient with increasing doses under the same load), and they were more fragile. These nano-mechanical changes in dental hard tissue may increase the susceptibility to caries. Radiotherapy caused nano-mechanical changes in dentine and enamel that were dose related. The key doses were 30-50 Gy and the key time points occurred during the 15th-25th days of treatment, which is when application of measures to prevent radiation caries should be considered. PMID- 26676191 TI - Evaluation of the relationship between the cost and properties of glass ionomer cements indicated for atraumatic restorative treatment. AB - The aim of this study was to evaluate microshear bond strength (MUSBS), water sorption and solubility of glass ionomer cements (GIC) indicated for atraumatic restorative treatment (ART). Cylindrical specimens (6 x 2.4 mm) were used to test the sorption and solubility of each GIC (n = 5). The specimens were weighed before and after immersion in water and desiccation. For the MUSBS test, 60 primary molars were ground to obtain flat surfaces from both enamel and dentin. The teeth were then assigned to the tested GIC (n = 10) groups, namely Fuji IX - FIX, Ketac Molar - KM and Maxxion R - MX. The exposed surfaces were pre-treated with GIC liquid. Polyethylene tubes were placed on the pre-treated surface and filled with one of the GIC. After 24 h, the specimens were submitted to the MUSBS test. The failure mode was assessed using a stereomicroscope (400 x magnification). The powder to liquid ratio and cost of material were also determined (n = 3). The data were analyzed by ANOVA and Tukey's post hoc test. Linear regression was used to determine the relation between cost and the other variables. Overall, MX showed lower MUSBS values (enamel: 3.93 +/- 0.38; dentin: 5.04 +/- 0.70) than FIX (enamel: 5.95 +/- 0.85; dentin: 7.01 +/- 1.06) and KM (enamel: 5.91 +/- 0.78; dentin: 6.88 +/- 1.35), as well as higher sorption and solubility. The regression analyses showed a significant and positive correlation between cost and MUSBS in enamel (R2 = 0.62; p < 0.001) and dentin (R2 = 0.43; p < 0.001); and a negative correlation between cost and water sorption (R2 = 0.93; p < 0.001) and solubility (R2 = 0.79; p < 0.001). In conclusion, the materials indicated for ART exhibit distinct physical and mechanical properties; in addition, low-priced materials may interfere with GIC properties. PMID- 26676193 TI - Evaluation of toothbrush disinfection via different methods. AB - The aim of this study was to compare the efficacy of using a dishwasher or different chemical agents, including 0.12% chlorhexidine gluconate, 2% sodium hypochlorite (NaOCl), a mouthrinse containing essential oils and alcohol, and 50% white vinegar, for toothbrush disinfection. Sixty volunteers were divided into five experimental groups and one control group (n = 10). Participants brushed their teeth using toothbrushes with standard bristles, and they disinfected the toothbrushes according to instructed methods. Bacterial contamination of the toothbrushes was compared between the experimental groups and the control group. Data were analyzed by Kruskal-Wallis and Duncan's multiple range tests, with 95% confidence intervals for multiple comparisons. Bacterial contamination of toothbrushes from individuals in the experimental groups differed from those in the control group (p < 0.05). The most effective method for elimination of all tested bacterial species was 50% white vinegar, followed in order by 2% NaOCl, mouthrinse containing essential oils and alcohol, 0.12% chlorhexidine gluconate, dishwasher use, and tap water (control). The results of this study show that the most effective method for disinfecting toothbrushes was submersion in 50% white vinegar, which is cost-effective, easy to access, and appropriate for household use. PMID- 26676194 TI - Maternal risk behavior and caries incidence in children with sickle cell disease. AB - The aim of this study was to analyze the incidence of caries, in relation to maternal risk behaviors and clinical conditions representing different levels of sickle cell disease severity. A total of 295 children aged 6 to 60 months participated in this cohort conducted from August 2007 to December 2008. They were diagnosed and monitored by the referral service of the state. Interviews were made with families to identify sociodemographic variables, and an oral exam was performed to determine dental caries. The SRQ (Self Report Questionnaire) scale was used to diagnose the presence of common mental disorders, and the CAGE (Cut down, Annoyed, Guilty and Eye opener) was applied to determine abusive use of alcohol. The absolute and relative frequencies of the variables of interest were analyzed by Chi-square and Mann-Whitney, with a 5% significance level. The incidence variables were analyzed according to the logistic regression model, with a confidence interval of 95%. Caries incidence (1.98; SD = 4.68) was higher in the HbSS genotype. There was a statistically significant association between caries incidence and both abusive use of alcohol (32.43%, RR = 1.99; 1.05-3.78; 95%CI) and common mental disorders (8.77% RR = 0.37; 0.15-0.93; 95%CI). There was also an association between caries incidence and maternal risk behavior, indicating that the care network should be expanded to include patients with sickle cell disease. PMID- 26676195 TI - Effect of green tea as a protective measure against dental erosion in coronary dentine. AB - The aim of this study was to evaluate the effect of green tea as a protective measure on eroded dentin. Disks of human coronary dentin were selected based on surface hardness and randomly assigned to 3 groups (n = 10): DW - distilled water, CHX - 0.2% chlorhexidine digluconate, and GT - green tea. The disks were allowed to acquire pellicle for 2 hours and were then subjected to 3 cycles per day of demineralization (C6H8O7 0.05 M, pH 3.75, 60 s), treatment (DW or CHX or GT, 5 min) and remineralization (artificial saliva, 60 min) over a period of 3 days. Changes in the dentin were determined by loss of surface hardness (%SHL) and mechanical profilometry analysis at the end of each day. Data were analyzed by two-way ANOVA followed by Tukey's test for %SHL and profilometry (p < 0.05). Significant reductions in dentin hardness loss were observed only for the CHX group when compared to the DW group (p < 0.05). However, there was no significant difference between the CHX and GT groups (p > 0.05). A significant difference was observed between DW and GT treatments for wear and roughness measurements (p < 0.05). The green tea extract solution was able to reduce the wear and roughness caused by dentin erosion under the conditions of this study. PMID- 26676196 TI - Evaluation of cutting ability and plastic deformation of reciprocating files. AB - This in vitro study evaluated the cutting ability of reciprocating files and the deformations caused by their multiple use. Five Reciproc(r) R25 files were divided into five groups for 10 simulated root canal preparations each. The resin blocks were weighed and photographed (12.5X and 20X) before and after preparation. The canals were prepared according to the manufacturer's instructions. Enlargement of the root canals was evaluated by comparison of pre- and post-preparation images using a computer software. The preoperative and postoperative weight differences determined the cutting ability of repeatedly used instruments. The data were analyzed using Lilliefors and Friedman statistical tests. The cutting ability and enlargement of the canals gradually decreased after each use, with significant differences observed at the 8th and 9th repetitions, respectively. There was no evidence of file deformation. The cutting ability and enlargement of the simulated canals gradually decreased when a reciprocating file was used up to 10 times. PMID- 26676197 TI - Prevalence of peri-implant disease on platform switching implants: a cross sectional pilot study. AB - The objective of this study was to assess the prevalence of mucositis and peri implantitis associated with the use of two types of implants-conventional versus platform switching after one year of loading. A longitudinal study of 64 implants in 25 patients was performed. Clinical variables, such as clinical pocket depth and bleeding upon probing, plaque, mobility, gingival recession, clinical attachment loss, and radiographic bone loss, were analyzed. The case definition for peri-implantitis was established as pockets of >= 5 mm with bleeding and bone loss >= 2 mm. One year after implant loading, the prevalence of mucositis and peri-implantitis with conventional implants (CIs) was 81.2% and 15.6%, respectively. For platform switching implants (PSIs) the prevalence was 90% and 6.6%, respectively. These differences were not statistically significant (p = 0.5375). However, there was a trend towards a lower prevalence of peri implantitis with platform switching Implants. PMID- 26676198 TI - Clinicopathological analysis of salivary gland tumors over a 15-year period. AB - Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions. PMID- 26676199 TI - Effect of thermoplastic filling techniques on the push-out strength of root sealing materials. AB - This study evaluates the effect of two thermoplastic obturation systems (MicroSeal and Obtura II) on bond strength of different sealers to intraradicular dentin. Sixty root canals of human canines were prepared using ProTaper rotary files (crown-down technique) and irrigated with 2.5% sodium hypochlorite and 17% EDTA. The root canals were filled by MicroSeal, Obtura II, or lateral compaction techniques using AH Plus and Epiphany SE. 1.5 mm thick root slices were subjected to the push-out test. ANOVA and Tukey's test showed that the bond strength values (MPa) observed in the groups obturated with MicroSeal (2.96 +/- 2.72) and Obtura II (2.68 +/- 2.18) did not significantly differ from each other (p > 0.05) but were significantly higher than that observed in the group obturated with lateral condensation (2.01 +/- 1.48; p < 0.05). There were no statistically significant differences in strength (p > 0.05) among the root canal thirds (cervical: 2.44 +/ 2.03; middle: 2.50 +/- 2.27; and apical: 2.70 +/- 2.34). Adhesive failures were predominant (60%) in all groups. In conclusion, MicroSeal and Obtura II techniques, using AH plus sealer, increased the resistance to displacement of the filling material, when compared with lateral compaction. Moreover, when used with Epiphany SE, these obturation systems did not affect the bond strength of the material to root dentin. PMID- 26676200 TI - Evaluation of the impact of orthognathic surgery on quality of life. AB - Dental treatment and surgery is a well-established method of correcting dentofacial deformities, and such treatment has an impact on the quality of life of individuals. The objective of this study was to evaluate the effect of orthognathic surgery on the quality of life of patients receiving treatment at the Universidade Federal do Parana - UFPR. Clinical data were evaluated for the control group, and a quality-of-life evaluation questionnaire was completed [Oral Health Impact Profile (OHIP-14)]. For the case group, the same data were gathered along with information regarding their dentofacial deformity. The OHIP-14 questionnaire was also completed at three distinct stages of the experiment. The median age in the control group was 23.5 years. In the case group, the predominant gender was female, and the mean age of patients was 29.4 years. There was a statistically significant association between gender and OHIP-14 (p< 0.001). No such association was observed between age and OHIP-14 scores (p= 0.616). In the control group the OHIP-14 median score was 11.5. In the case group, the average OHIP-14 score at was 18 at T0, 21 at T1, and 8 at T2. The results demonstrated a statistically significant association between the three time stages at which OHIP-14 was analyzed (p< 0.001). There was a smaller reduction in the negative impact for transversal deformities of the jaw when compared with other deformities. Orthognathic surgery led to a reduction in the negative effects on the quality of life of patients. PMID- 26676202 TI - Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer. AB - BACKGROUND: This is the second update of the review first published in the Cochrane Database of Systematic Reviews in 2009, Issue 1. Epithelial ovarian cancer is diagnosed in over 200,000 women worldwide each year. Ten to 20% of women are diagnosed early, when there is still a good possibility of cure. The treatment of early-stage (stage I and IIa) disease involves surgery to remove the disease, often followed by chemotherapy (adjuvant chemotherapy). The largest clinical trials of adjuvant chemotherapy show an overall survival (OS) advantage with platinum-based chemotherapy; however the precise role and type of this treatment in subgroups of women with differing prognoses needs to be defined. OBJECTIVES: To undertake a systematic review of the evidence for adjuvant chemotherapy in early-stage epithelial ovarian cancer to determine whether chemotherapy following surgery offers a survival advantage over the policy of observation following surgery (with chemotherapy reserved for treatment of disease recurrence); and to determine if clinical subgroups of women with differing prognoses, based on histological subtype or completeness of surgical staging, have more or less to gain from adjuvant chemotherapy. SEARCH METHODS: We performed an electronic search using the Cochrane Gynaecological Cancer Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 3), MEDLINE (1948 to March week 5, 2015), and EMBASE (1980 to week 14, 2015). We developed the search strategy using free-text and medical subject headings (MeSH). We also searched registers of clinical trials and citation lists of included studies for potentially relevant studies. SELECTION CRITERIA: We included randomised clinical trials (RCTs) of women with early stage (I/IIa) epithelial ovarian cancer staged at laparotomy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality of included RCTs. We resolved any disagreements by discussion with a third review author. We used random-effects methods for all meta-analyses, including subgroup analyses. MAIN RESULTS: The original version of this Cochrane review included five RCTs involving 1277 women. In this 2015 update, no new studies met the inclusion criteria but we included an additional paper with mature data (10-year follow-up) relating to a previously included study (ICON1).We included four studies in the meta-analyses and considered them to be at a low risk of bias. Most study participants (> 95%) had stage I ovarian cancer. Meta-analysis of five year data from three studies indicated that women who received adjuvant platinum based chemotherapy had better overall survival (OS) than those who did not (Hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.93; 1008 women; 3 studies; I2 statistic = 0%; high quality evidence). Likewise, meta-analysis of five-year data from four studies indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67, 95% CI 0.53 to 0.84; 1170 women, 4 studies; I2 statistic = 0%; high quality evidence). These findings were robust over time, with 10-year HR estimates of 0.72 (95% CI 0.57 to 0.92; 925 women, 2 studies) and 0.67 (95% CI 0.53 to 0.83; 925 women, 2 studies) for OS and PFS, respectively (high quality evidence). The risk of death at 10 years follow-up favoured the adjuvant chemotherapy arm (0.76, 95% CI 0.62 to 0.94; 923 women, 2 studies; I2 statistic = 0%), as did the findings for risk of progression at 10 years (RR 0.72, 95% CI 0.60 to 0.87; 925 women, 2 studies; I2 statistic = 0%). Low quality evidence suggested that women with high-risk disease may have the most to gain from adjuvant chemotherapy. However, subgroup analyses could neither confirm nor exclude survival benefits in lower risk disease or in optimally staged disease. We found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups. AUTHORS' CONCLUSIONS: High-quality evidence indicates that adjuvant platinum-based chemotherapy is effective in prolonging survival in women with early stage (FIGO stage I/IIa) epithelial ovarian cancer. It remains uncertain whether women with low- and intermediate-risk early stage disease will benefit as much from adjuvant chemotherapy as women with high-risk disease. Decisions to use adjuvant chemotherapy (AC) in these women should be mindful of this uncertainty, and the uncertainty regarding adverse events. Treatment of women with lower risk disease should be individualised to take into account individual factors. PMID- 26676201 TI - Psychotherapeutic Intervention in the Demobilization Process: Addressing Combat related Mental Injuries with Narrative Exposure in a First and Second Dissemination Stage. AB - BACKGROUND: Depending on the exposure to traumatic stressors and combat, 20% to 50% of ex-combatants present with trauma-related disorders, and more than half of the members of armed groups have a proclivity to violence. Therefore, psychotherapeutic assistance should address both, trauma-related suffering and the lowered threshold for aggressive behaviour. OBJECTIVE: Supporting the demobilization process of ex-combatants in the eastern DR-Congo, we implemented a version of Narrative Exposure Therapy adapted for Forensic Offender Rehabilitation (FORNET). METHOD: In two successive dissemination stages (DS), local counsellors conducted FORNET. In DS1, they were trained by clinical experts, and in DS2, the by then experienced counsellors trained and supervised a second group of local counsellors (DS2). The training consisted of a 3-week workshop covering theoretical concepts and practical therapeutic skills. In DS1 and DS2, a total of 98 demobilizing combatants received an intervention; treatment-as-usual served as the control condition. Posttraumatic stress disorder, appetitive aggression, depression severity and drug dependence were assessed prior to the intervention and 6 and 12 months later; additionally, we assessed reintegration success. RESULTS: Six months post-intervention, FORNET significantly reduced Posttraumatic stress disorder symptoms but had less effect on the trait of appetitive aggression; moreover, beneficial effects were found for depression severity and drug dependence as well as for reintegration indices. Treatment gains were retained at 12 months. CONCLUSIONS: Individuals without previous training in psychotherapy can learn to effectively apply the brief intervention FORNET and support the demobilization process in ongoing conflicts. The study suggests that it is possible to pass down psychotherapeutic techniques over generations of counsellors. (c) 2015 The Authors. Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd. KEY PRACTITIONER MESSAGE: Posttraumatic stress symptoms, depression and clinically relevant levels of drug dependence can effectively be reduced with a version of Narrative Exposure Therapy (NET) adapted for Forensic Offender Rehabilitation (FORNET). The intervention is effective in the context of ongoing conflict. Individuals without previous training in psychotherapy can learn to effectively apply the brief intervention FORNET. It is possible to pass down psychotherapeutic techniques like FORNET over generations of counsellors. Psychotherapeutic interventions like FORNET may facilitate the transition to peace in war-torn regions. PMID- 26676203 TI - Immediate Implants Placed in Fresh Sockets Associated with Periapical Pathology: A Split-Mouth Design and Survival Evaluation after 1-Year Follow-Up. AB - PURPOSE: To compare the immediate implant success rates between sites with chronic apical lesions and healthy sites in the same patients 1 year postdelayed loading. MATERIALS AND METHODS: One hundred sixty-eight immediate implants were placed in sixty patients at upper incisor, canine, and premolar sites. A split mouth design was used, placing a minimum of two implants, one in a fresh socket associated with chronic periapical disease, the average lesion size was larger than 4 mm and less than 8 mm (test group), and the other(s) in a healthy fresh socket (control group). Implant survival rate at 1 year postloading delayed was compared between the groups. RESULTS: The implant survival rate was 98.2% for the total sample (n = 168); out of the three implants lost, two were from the test group, and one was from the control group (in the same patient as one of the former). Among the surviving implants, five were also considered failures due to excessive bone loss (n = 3) and also because of the recurrence of the periapical lesions (n = 2). Survival rates were significantly lower in the test than control sites at 12 months postloading. CONCLUSIONS: Implant survival rates were significantly lower after the immediate implantation in postextraction sockets associated with chronic periapical disease (90.8%) than in healthy postextraction sockets (98.1%). PMID- 26676204 TI - Integrative genomic analysis of interleukin-36RN and its prognostic value in cancer. AB - Interleukin (IL)-36RN, previously known as IL1-F5 and IL-1delta, shares a 360-kb region of chromosome 2q13 with members of IL-1 systems. IL-36RN encodes an anti inflammatory cytokine, IL-36 receptor antagonist (IL-36Ra). In spite of IL-36Ra showing the highest homology to IL-1 receptor (IL-1R) antagonist, it differs from the latter in aspects including its binding to IL-lRrp2 but not to IL-1R1. IL 36RN is mainly expressed in epithelial cells and has important roles in inflammatory diseases. In the present study, IL-36RN was identified in the genomes of 27 species, including human, chimpanzee, mouse, horse and dolphin. Human IL-36RN was mainly expressed in the eye, head and neck, fetal heart, lung, testis, cervix and placenta; furthermore, it was highly expressed in bladder and parathyroid tumors. Furthermore, a total of 30 single nucleotide polymorphisms causing missense mutations were determined, which are considered to be the causes of various diseases, such as generalized pustular psoriasis. In addition, the link between IL-36RN and the prognosis of certain cancer types was revealed through meta-analysis. Tumor-associated transcriptional factors c-Fos, activator protein-1, c-Jun and nuclear factor kappaB were found to bind to the upstream region in the IL-36RN gene. This may indicate that IL-36RN is involved in tumorigenesis and tumor progression through the regulation of tumor-associated transcriptional factors. The present study identified IL-36RN in various species and investigated the associations between IL-36RN and cancer prognosis, which would determine whether IL-36RN drove the evolution of the various species with regard to tumorigenesis. PMID- 26676205 TI - Redefinition of Skin Cancer as a Chronic Disease. PMID- 26676206 TI - Building a Better Halide Receptor: Optimum Choice of Spacer, Binding Unit, and Halosubstitution. AB - Quantum calculations are used to measure the binding of halides to a number of bipodal dicationic receptors, constructed as a pair of binding units separated by a spacer group. A number of variations are studied. A H atom on each binding unit (imidazolium or triazolium) is replaced by Br or I. Benzene, thiophene, carbazole, and dimethylnaphthalene are considered as spacer groups. Each receptor is paired with halides F(-) , Cl(-) , Br(-) , and I(-) . Substitution with I on the binding unit yields a large enhancement of binding, as much as 13 orders of magnitude; a much smaller increase occurs for substitution with Br. Imidazolium is a more effective binding agent than is triazolium. Benzene and dimethylnaphthalene represent the best spacers, followed by thiophene and carbazole. F(-) binds much more strongly than do the other halides, which obey the order Cl(-) >Br(-) >I(-) . PMID- 26676208 TI - You want your students and colleagues to publish? Then mentor them!!! PMID- 26676209 TI - Nonvitamin K antagonist oral anticoagulants in everyday practice: Stroke prevention in atrial fibrillation and treatment of venous thromboembolism. AB - PURPOSE: In recent years, four nonvitamin K antagonist oral anticoagulants (NOACs) were approved to prevent stroke in patients with nonvalvular atrial fibrillation (AF) and to treat venous thromboembolism (VTE). Edoxaban, a direct factor Xa inhibitor, is the latest NOAC to be approved for use by the U.S. Food and Drug Administration. The other NOACs include two direct factor Xa inhibitors, apixaban and rivaroxaban, and one direct thrombin inhibitor, dabigatran. The purpose of this article is to introduce these agents to providers, discuss dosing, and offer insights into practical considerations for each NOAC. DATA SOURCES: PubMed was searched to identify randomized controlled trials and cost effectiveness analyses evaluating NOACs. In addition, package inserts for the four NOACs provided pharmacologic data. CONCLUSIONS: All four NOACs are equivalent to or better than warfarin for the treatment of VTE and stroke prevention in AF, and may reduce the risk of bleeding complications, particularly intracranial bleeding. IMPLICATIONS FOR PRACTICE: NOACs may benefit some patients by avoiding the numerous food or drug interactions and frequent laboratory monitoring associated with warfarin. Adherence to proper dosing is critical for NOAC efficacy and safety. PMID- 26676210 TI - Serum Parathyroid Hormone Concentrations and Clinical Outcomes in ESRD: A Call for Targeted Clinical Trials. AB - Secondary hyperparathyroidism almost universally accompanies end-stage renal disease (ESRD). In some, but not all studies, elevated serum parathyroid hormone (PTH) concentrations are associated with increased fracture rates, cardiovascular disease, and mortality in ESRD. The serum concentration of PTH required for optimal bone health and reduced cardiovascular risk in such patients remains elusive. Recent clinical trials have failed to show substantial changes in morbidity and mortality following reductions of elevated serum PTH concentrations. In this review, we will assess some of the difficulties in evaluating elevated serum PTH concentrations, and their association with skeletal fractures and mortality in ESRD patients. We are of the opinion that in the context of ESRD, elevated PTH concentrations occur in conjunction with other comorbid conditions such as diabetes mellitus, malnutrition, hypertension, volume excess, preexisting heart disease, all of which have prevented establishing a precise association between elevated serum PTH concentrations and global or skeletal outcomes. Age, gender, and racial variability among groups make interpretation exceptionally difficult. Analysis of prevalent ESRD populations with secondary hyperparathyroidism should take all these factors into account. We suggest that future clinical trials which examine the usefulness of reductions in serum PTH concentrations be conducted in age, sex, and racially balanced groups, without or with minimal coexisting confounding disease. Furthermore, trials in such populations should have as their primary outcome a reduction in fractures rather than an alteration in mortality. PMID- 26676211 TI - Light Responsive Microstructured Surfaces of Liquid Crystalline Network with Shape Memory and Tunable Wetting Behaviors. AB - Using adaptive soft materials to fabricate microstructured surfaces renders them with tunable topographic feature and thus controllable physical properties. Here, light responsive microstructured surfaces are reported with shape memory and tunable wetting behaviors; the surfaces are covered with micropillar arrays and constructed by lightly crosslinked azo-containing liquid crystalline network (LCN). UV light irradiation induces 25% contraction in length of the micropillars along their long axes and, as a consequence, the variations of topographic feature and wetting behavior of the surfaces. In addition, the LCNs exhibit shape memory properties, which can freeze the temporary topographic feature of microstructured surfaces (formed under UV irradiation and relatively high temperature) and enable application of their functionalities at mild conditions. This light responsiveness makes it feasible to remotely and precisely tune the local regions of microstructured surfaces, which should broaden the applications of adaptive surfaces in regulating the wetting, optical, and adhesion properties in selected regions. PMID- 26676212 TI - Bone Marrow-Derived Cells Implanted into Freeze-Injured Urinary Bladders Reconstruct Functional Smooth Muscle Layers. AB - Regenerative medicine offers great hope for lower urinary tract dysfunctions due to irreversibly damaged urinary bladders and urethras. Our aim is the utilization of bone marrow-derived cells to reconstruct smooth muscle layers for the treatments of irreversibly damaged lower urinary tracts. In our mouse model system for urinary bladder regeneration, the majority of smooth muscle layers in about one-third of the bladder are destroyed by brief freezing. Three days after wounding, we implant cultured cells derived from bone marrow. The implanted bone marrow-derived cells survive and differentiate into layered smooth muscle structures that remediate urinary dysfunction. However, bone marrow-derived cells implanted into the intact normal urinary bladders do not exhibit these behaviors. The presence of large pores in the walls of the freeze-injured urinary bladders is likely to be helpful for a high rate of survival of the implanted cells. The pores could also serve as scaffolding for the reconstruction of tissue structures. The surviving host cells upregulate several growth factor mRNAs that, if translated, can promote differentiation of smooth muscle and other cell types. We conclude that the multipotency of the bone marrow-derived cells and the provision of scaffolding and suitable growth factors by the microenvironment enable successful tissue engineering in our model system for urinary bladder regeneration. In this review, we suggest that the development of regenerative medicine needs not only a greater understanding of the requirements for undifferentiated cell proliferation and targeted differentiation, but also further knowledge of each unique microenvironment within recipient tissues. PMID- 26676213 TI - Conversion to Silodosin in Men on Conventional alpha1 -Blockers for Symptomatic Benign Prostatic Hyperplasia. AB - OBJECTIVES: alpha1 -blockers have commonly been used as first-line medical therapy for symptomatic benign prostatic hyperplasia (BPH). Recently, a highly selective alpha1A -adrenoceptor antagonist, silodosin, was developed in Japan. We examined the efficacy and safety of conversion from conventional alpha1 -blockers to silodosin in men with BPH. METHODS: Conversion to silodosin was proposed to consecutive patients on conventional alpha1 -blockers for symptomatic BPH for at least 6 months. The effects of conversion were examined by the International Prostate Symptom Score, quality of life index, overactive bladder symptom score, peak flow rate, residual urine volume, and adverse events at 12 weeks. The efficacy of silodosin was also evaluated by patients' impression. RESULTS: Eighty one men underwent conversion, for the most part because of dissatisfaction with the efficacy of their current treatment in improving nocturia or weak stream. The International Prostate Symptom Score total score significantly improved from 12.7 +/- 5.9 at baseline to 10.6 +/- 5.4 at 4 weeks (P < 0.001) and 10.9 +/- 5.8 at 12 weeks (P < 0.01). The progress was mostly due to improvement in voiding symptoms, although reduction of storage symptoms was also significant. The quality of life index also significantly decreased with conversion to silodosin. Efficacy as judged by patients' impression was 76% (37/49) at 12 weeks of treatment. None of the overactive bladder symptom score, peak flow rate, and residual urine volume exhibited significant change. No serious adverse events were observed during the study period. CONCLUSION: Conversion to silodosin may be beneficial in men who are dissatisfied with conventional alpha1 -blockers for BPH, and be particularly useful in improving voiding symptoms. PMID- 26676214 TI - Influence of Body Position on Defecation in Humans. AB - OBJECTIVES: To compare three positions for defecation by measuring abdominal pressure and the anorectal angle simultaneously. METHODS: We recruited six healthy volunteers. The videomanometric measures included simultaneous fluoroscopic images, abdominal pressures, subtracted rectal pressures and anal sphincter pressures. Three positions were used: sitting, sitting with the hip flexing at 60 degrees with respect to the rest of the body, and squatting with the hip flexing at 22.5 degrees with respect to the rest of the body. RESULTS: Basal abdominal pressure before defecation on hip-flex sitting was lower than that with normal sitting, although the difference did not reach statistical significance. Basal abdominal pressure before defecation on squatting (26 cmH2 O) was lower than that with normal sitting (P < 0.01). Abdominal pressure increase (strain) on hip-flex sitting was lower than that with normal sitting, although this difference did not reach statistical significance. Similarly, the abdominal pressure increase on squatting was smaller than that with normal sitting, and yet the difference did not reach statistical significance. The rectoanal angle on defecation on hip-flex sitting did not differ from that with normal sitting. The rectoanal angle on defecation on squatting (126 degrees ) was larger than that with normal sitting (100 degrees ) (P < 0.05), and was also larger than that with hip-flex sitting (99 degrees ) (P < 0.01). CONCLUSION: The results of the present study suggest that the greater the hip flexion achieved by squatting, the straighter the rectoanal canal will be, and accordingly, less strain will be required for defecation. PMID- 26676215 TI - Simultaneous Treatment of Female Urethral Diverticulum and Stress Urinary Incontinence with Urethral Diverticulectomy and Suburethral Synthetic Mesh Sling. AB - OBJECTIVES: Pubovaginal fascial sling along with urethral diverticulectomy has been advised as the most appropriate anti-incontinence procedure for female stress urinary incontinence (SUI) with concomitant urethral diverticula (UD). We believe that suburethral synthetic mesh tape sling can also be safely used in some patients with concomitant SUI and UD. Herein, we present our experience for simultaneous treatment of UD and SUI with urethral diverticulectomy and suburethral synthetic mesh tape sling. METHODS: From 2003 to 2008, there are three patients with UD and SUI in our institution. They received transvaginal urethral diverticulectomy and suburethral synthetic mesh tape sling simultaneously. Videourodynamics was done before and three months after the surgery. RESULTS: Preoperative pelvis magnetic resonance imaging and videourodynamic study showed UD over distal urethra and SUI in all three patients. Urinalysis disclosed mild pyuria in two of the patients, and they both received intravenous antibiotics treatment to eradicate the infection prior to the surgery. They all underwent urethral diverticulectomy with suburethral synthetic mesh tape sling. The postoperative videourodynamic study showed no recurrence of UD and SUI. With a mean follow up of 33.3 months, there was no infection or exposure of synthetic mesh tape. CONCLUSIONS: In patients with UD and SUI, suburethral sling using synthetic mesh can be as effective and safe as facial sling in selected patients. PMID- 26676216 TI - Influence of Urethral Sphincter Incompetence on Bladder Shape and Function in Myelodysplastic Children. AB - OBJECTIVES: This study was undertaken to investigate the influence of the urethral function on bladder shape and function in myelodysplastic children. METHODS: Of 39 myelodysplastic children, 30 were treated with intermittent catheterization. The diagnosis of internal sphincter incompetence (SI) was based on cystographic findings (open bladder neck) and that of external SI on urodynamic findings (underactive external sphincter identified on electromyography and maximum urethral closure pressure of less than 50 cm H2 O). Follow up included evaluation of bladder deformity and compliance. RESULTS: The mean observation period was 8.6 years. In the 11 patients with external SI, bladder deformity and compliance significantly improved as a result of intermittent catheterization. However, of 12 patients with overactive sphincter and/or closure pressure of 50 cm H2 O or more, eight showed deterioration or no improvement in bladder deformity, and three showed upper urinary tract deterioration. CONCLUSION: These results indicate that an increase in urethral resistance may lead to deterioration of bladder shape. PMID- 26676217 TI - Effects of Silodosin on Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia: Evaluation by Frequency/Volume Chart. AB - OBJECTIVES: To prospectively evaluate the efficacy of silodosin, a new alpha1A adrenoceptor selective antagonist, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) on the basis of a frequency/volume chart. METHODS: Forty male patients (71.1 +/- 6.6 years old) with LUTS/BPH were treated with silodosin (4 mg twice daily). The effects of the drug were assessed by changes in International Prostate Symptom Score, uroflowmetry, and frequency/volume chart at 1 and 3 months after therapy. RESULTS: The mean total International Prostate Symptom Score, the mean total storage and voiding scores and the mean quality of life score decreased significantly at 1 and 3 months after therapy (all P < 0.01). Average and maximum flow rates increased significantly, and postvoid residual volume decreased significantly after 1 and 3 months (all P < 0.05). The frequency/volume chart showed that daytime frequency in those who initially voided over eight times/day (n = 12) decreased significantly (P = 0.0391) after 1 month, and nighttime frequency in those who initially voided over two times (n = 16) tended to decrease (P = 0.0833) after 3 months. Mean voided volume in those who initially voided less than 250 mL (n = 31) increased significantly after 1 and 3 months (P = 0.0446 and P = 0.0138, respectively), and maximum voided volume in those who initially voided less than 300 mL (n = 18) tended to increase (P = 0.0833) after 1 month. CONCLUSION: Silodosin appears to be effective for both storage and voiding symptoms by increasing bladder capacity in patients with LUTS/BPH. PMID- 26676218 TI - Prospective Study Comparing the Suprapubic Arc (Sparc) Procedure and the Transobturator (Monarc) Procedure for Treating Female Stress Urinary Incontinence. AB - OBJECTIVES: In a comparative trial we evaluated the efficacy and safety of the suprapubic arch (Sparc) and transobturator (Monarc) procedures for the treatment of female stress urinary incontinence (SUI). METHODS: Between November 2003 and May 2004, 46 women with SUI who underwent the Sparc procedure and 42 women who underwent the Monarc procedure were analyzed. The preoperative evaluation included history taking, physical examination, voiding diary, stress and 1-h pad tests and a comprehensive urodynamic examination. Postoperative evaluation included a stress test, 1-h pad test, and uroflowmetry with postvoid residuals. RESULTS: After 1 year of follow up, the rates of cure and satisfaction were 93.5 and 93.0%, respectively, in the Sparc group. The rates of cure and satisfaction were 95.2 and 85.7%, respectively, in the Monarc group. After 2 years of follow up, the rates of cure (93.5 vs 92.9%) and satisfaction (84.8 vs 83.3%) were similar between the two groups. No bladder injury occurred in the Monarc group. Bladder injury occurred in 6.5% (n = 3) of the patients in the Sparc group. Vaginal wall perforation occurred in 4.8% (n = 2) of the patients in the Monarc group (P > 0.05). Late complications included de novo urge symptoms (8.7 vs 11.9%) and voiding dysfunction (10.9 vs 9.5%). CONCLUSIONS: The transobturator Monarc procedure appears to be as efficient and safe as the retropubic Sparc procedure for the treatment of SUI. PMID- 26676219 TI - Muscarinic Receptor Binding and Plasma Drug Concentration after the Oral Administration of Propiverine in Mice. AB - OBJECTIVES: The current study was undertaken to characterize the binding of propiverine to muscarinic receptors in mouse tissues by measuring plasma concentrations of the drug and its metabolite. METHODS: At 0.5-24 h after the oral administration of propiverine at pharmacologically relevant doses, muscarinic receptors in tissue homogenates were measured by a radioligand binding assay using [N-methyl- (3) H]scopolamine (NMS), along with the drug's concentration in plasma by the liquid chromatography-tandem mass spectrometric method. RESULTS: In the in vitro experiments, propiverine and its metabolite 1 methy-4-piperidyl benzilate N-oxide competed with [(3) H]NMS for binding sites in the bladder, submaxillary gland and heart of mice in a concentration-dependent manner. After the oral administration of propiverine, dose- and time-dependent increases in the dissociation constant for specific [(3) H]NMS binding were observed in the bladder and other tissues of mice, indicating that orally administered propiverine and/or its metabolite undergo significant binding to muscarinic receptors in mouse tissues. A longer-lasting binding of muscarinic receptor was seen in the bladder than in the submaxillary gland at relatively low doses of propiverine. Furthermore, the decrease in maximal number of binding sites values for [(3) H]NMS binding was more remarkable in the bladder than submaxillary gland of propiverine treated mice. There was a dose-dependent rise in the plasma concentrations of propiverine and 1-methy-4-piperidyl benzilate N oxide in mice after the oral administration of propiverine. CONCLUSION: The oral administration of propiverine exerts a more prominent and longer-lasting effect in the bladder than in the submaxillary gland of mice. The N-oxide metabolite may contribute significantly to the blockade of muscarinic receptors caused by oral propiverine. PMID- 26676220 TI - Cinnamomum verum Component 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo. AB - Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2 methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-kappaB (NF-kappaB) and both topoisomerase I and II activities. Further study reveals that the growth inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-kappaB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2 MCA could be a potential agent for anticancer therapy. PMID- 26676221 TI - Hepatocellular Cancer: New Kids on the Block. AB - BACKGROUND: With over 600,000 newly diagnosed hepatocellular cancer (HCC) patients worldwide every year and ongoing clinical research, it is surprising that many of the new molecular entities have not yet resulted in significant prolongation of progression-free or overall survival. Nevertheless, there are a number of promising agents currently under investigation. Given the unique tumor biology and heterogeneous clinical manifestations of HCC, the application of molecular and cellular markers could also benefit patient selection, disease prognosis and trial design. SUMMARY: This paper provides an overview of the current therapeutic strategies for HCC in the curative and palliative settings. Furthermore, we introduce some of the promising small molecules and antibodies that may find their way into clinical practice, with a focus on substances that are currently in phase III testing. Finally, we summarize the role of promising biomarkers, such as circulating tumor or cancer stem cells. KEY MESSAGE: Despite the rising prevalence of HCC and active clinical research, few therapeutic options besides sorafenib have been established. This review discusses the new therapeutic agents in the pipeline. PRACTICAL IMPLICATIONS: Although many promising preclinical studies have resulted in phase I-II trials on HCC, so far only the tyrosine and Raf kinase inhibitor sorafenib has made its way into the hands of physicians. This multikinase inhibitor is the only approved option for systemic treatment of advanced HCC. Currently, the development of promising approaches for disease management is guided by biomarkers such as molecular markers or cellular characteristics. The use of biomarkers may facilitate early diagnosis in high-risk groups and therefore enhance outcomes by detecting patients whose disease is still curable. PMID- 26676222 TI - Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells. AB - The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs. PMID- 26676224 TI - An Unusual Case of Small Bowel Volvulus. AB - Small bowel volvulus is a rare and life threatening surgical emergency. Nearly 75% of volvulus occurs in colon and 25% occurs in small bowel. Small bowel volvulus is abnormal twisting of bowel loops around the axis of its own mesentry leading to twisting and occlusion of mesenteric vessels causing intestinal obstruction, venous engorgement, gangrene and perforation. Small bowel volvulus is more common in neonates and young adults and very rare in adults. We are reporting a first case of small bowel volvulus and gangrene caused by herniation of ovarian cyst through mesenteric defect and twisting of small bowel around the axis of ovarian cyst leading to closed loop obstruction, small bowel volvulus and gangrene. Outcome of the disease is mainly based on the early diagnosis and intervention. Mortality is about 5.8 - 8% in nongangrenous SBV which increases drastically to 20 - 100% in gangrenous bowel. PMID- 26676223 TI - Effects of oral cyclosporine on canine T-cell expression of IL-2 and IFN-gamma across a 12-h dosing interval. AB - The duration of immunosuppressive effects following oral cyclosporine in dogs is unknown. This study used flow cytometry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to evaluate the effects of high-dose oral cyclosporine across a 12-h dosing interval. Expression of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was compared before and after 8 days of cyclosporine at 10 mg/kg every 12 h in six healthy dogs. Samples were collected at 0, 2, 4, and 8 h postdosing for analysis of unactivated and activated T-cell and whole blood cytokine expression using flow cytometry and qRT-PCR, respectively, and at 0, 2, 4, 6, 8, and 10 h postdosing for measurement of cyclosporine concentrations. Flow cytometry and qRT-PCR both demonstrated significant marked reductions in IL-2 and IFN-gamma levels at 0, 2, 4, and 8 h after dosing compared to pretreatment levels (P < 0.05) for activated samples, with less consistent effects observed for unactivated samples. Both flow cytometry and qRT-PCR are viable techniques for measuring cyclosporine pharmacodynamics in dogs, yielding comparable results with activated samples. Two hours postdrug administration is the preferred time for concurrent assessment of peak drug concentration and cytokine expression, and T-cell activation is needed for optimal results. PMID- 26676225 TI - Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer. AB - Colorectal cancer is a common malignant disease, the incidence of which is increasing worldwide, therefore, identifying novel prognostic factors to improve adjuvant therapeutic strategies or postoperative monitoring is required. Angiogenesis, which is assessed by microvessel density (MVD), is significant in tumor growth and metastasis. However, the association between angiogenesis and clinical outcome remains controversial. In the present study, 84 surgically resected cases of colorectal cancer were examined to clarify the clinicopathological significance of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cluster of differentiation (CD)34 expression levels. VEGF expression was identified to be significantly correlated with TP expression (r=0.45; P<0.0001) and MVD in the high VEGF expression group was observed to be significantly greater than that in the low VEGF expression group (P=0.0194). In the Dukes' stage D group, the MVD in the high TP expression group was significantly greater than that in the low TP expression group (P=0.0149). High VEGF expression was subsequently correlated with a short overall survival rate for patients exhibiting lymph node metastasis (P=0.0128); however, there was no significant difference in overall survival rate regarding the expression levels of TP and CD34. The results of the present study indicate that VEGF expression may serve as a prognostic factor for colorectal cancer patients exhibiting lymph node metastasis. Furthermore, angiogenesis, as assessed by MVD, is an important prognostic factor for tumor growth at the primary site. PMID- 26676227 TI - Selective A3 adenosine receptor agonist protects against doxorubicin-induced cardiotoxicity. AB - PURPOSE: Doxorubicin (DOX) is an effective anticancer drug; however, its clinical use is limited by its cardiotoxic effect. Adenosine was proved to mediate anti inflammatory effects and protected from myocardial ischemia/reperfusion injury. So the present work was designed to examine the effectiveness of a selective A3 adenosine receptor agonist (Cl-IB-MECA) in DOX-induced cardiotoxicity and to elucidate the underlying mechanisms via studying its effect on different oxidative stress, inflammatory and apoptotic markers. METHODS: Firstly the potential cardioprotective dose of Cl-IB-MECA was screened in male Wistar rats at different doses (20, 40 and 80 ug/kg; i.v) against a single dose of DOX (15 mg/kg; i.p). Secondly, the dose of 40 ug/kg Cl-IB-MECA was selected for further assessment of the cardioprotective mechanisms. RESULTS: Cl-IB-MECA at a dose 40 ug/kg (i.v) protects against DOX-induced bradycardia, elevated creatine kinase isoenzyme-MB and histopathological changes. Also, it significantly ameliorates oxidative stress injury evoked by DOX as evidenced by inhibition of reduced glutathione depletion and lipid peroxidation as well as elevation of antioxidant enzyme activities. Additionally, DOX provoked inflammatory responses by increasing the expressions of nuclear factor kappa B and the levels of tumor necrosis factor alpha. Cl-IB-MECA pretreatment significantly inhibited these inflammatory responses. Furthermore, DOX induced apoptotic tissue damage by increasing cytochrome c expressions which was suppressed by Cl-IB-MECA pretreatment. CONCLUSION: Cl-IB-MECA protects against DOX-induced cardiotoxicity through restoration of the oxidant/antioxidant status and consequential suppression of DOX-induced inflammatory responses and abrogation of the resultant apoptotic signals. PMID- 26676228 TI - Sevoflurane or desflurane: Which one is more expensive? PMID- 26676229 TI - Limiting the accessibility of cost-prohibitive drugs: The story is incomplete. PMID- 26676226 TI - Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo. AB - Subarachnoid hemorrhage causes acute and long-lasting constrictions of pial arterioles. Whether these vessels dilate normally to neuronal activity is of great interest since a mismatch between delivery and consumption of glucose and oxygen may cause additional neuronal damage. Therefore, we investigated neurovascular reactivity of pial and parenchymal arterioles after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to subarachnoid hemorrhage by filament perforation or sham surgery. Neurovascular reactivity was assessed 3 h later by forepaw stimulation or inhalation of 10% CO2 Diameters of cerebral arterioles were assessed using two-photon microscopy. Neurovascular coupling and astrocytic endfoot Ca2+ were measured in brain slices using two-photon and infrared-differential interference contrast microscopy. Vessels of sham-operated mice dilated normally to CO2 and forepaw stimulation. Three hours after subarachnoid hemorrhage, CO2 reactivity was completely lost in both pial and parenchymal arterioles, while neurovascular coupling was not affected. Brain slices studies also showed normal neurovascular coupling and a normal increase in astrocytic endfoot Ca2+ acutely after subarachnoid hemorrhage. These findings suggest that communication between neurons, astrocytes, and parenchymal arterioles is not affected in the first few hours after subarachnoid hemorrhage, while CO2 reactivity, which is dependent on NO signaling, is completely lost. PMID- 26676230 TI - Mutation of EMG1 causing Bowen-Conradi syndrome results in reduced cell proliferation rates concomitant with G2/M arrest and 18S rRNA processing delay. AB - Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder caused by a D86G substitution in the protein, Essential for Mitotic Growth 1 (EMG1). EMG1 is essential for 18S rRNA maturation and 40S ribosome biogenesis in yeast, but no studies of its role in ribosome biogenesis have been done in mammals. To assess the effect of the EMG1 mutation on cell growth and ribosomal biogenesis in humans, we employed BCS patient cells. The D86G substitution did not interfere with EMG1 nucleolar localization. In BCS patient lymphoblasts, cells accumulated in G2/M, resulting in reduced proliferation rates; however, patient fibroblasts showed normal proliferation. The rate of 18S rRNA processing was consistently delayed in patient cells, although this did not lead to a difference in the levels of 40S ribosomes, or a change in protein synthesis rates. These results demonstrate that as in yeast, EMG1 in mammals has a role in ribosome biogenesis. The obvious phenotype in lymphoblasts compared to fibroblasts suggests a greater need for EMG1 in rapidly dividing cells. Tissue-specific effects have been seen in other ribosomal biogenesis disorders, and it seems likely that the impact of EMG1 deficiency would be larger in the rapidly proliferating cells of the developing embryo. PMID- 26676231 TI - Effect of Thiocyanate on Iodine Status of Pregnant Women. AB - The aim of this study was to assess the thyroid status of pregnant women on the basis of biochemical indicators and to evaluate the potential risk of developing iodine deficiency as a result of tobacco smoke exposure by assessing the association between urinary thiocyanate levels and the manifestation of iodine deficiency. The study included 219 pregnant women from the town of Plovdiv and Plovdiv District in Southern Bulgaria. The levels of urinary iodine, thyroid stimulating hormone (TSH), free thyroxine (FT4), and urinary thiocyanate as indicators of tobacco smoke exposure were measured. Most of the pregnant women (60.1 %) were found to have iodine deficiency, 10.6 % of them had TSH values greater than 4 mIU/L, and 16.4 % had FT4 below 9 pmol/L. There were negative correlations between urinary iodine levels and thiocyanate/creatinine ratio (R = 0.148, r = 0.034) and between thiocyanate/creatinine ratio and FT4 (R = -0.379, p < 0.0001); thiocyanate/creatinine ratio and serum TSH were positively correlated (R = 0.169, p = 0.019). Logistic regression analysis showed that pregnant women in whom the thiocyanate/creatinine ratio was greater than the median value of 3.57 mg/g had a 3.882-fold higher risk of developing iodine deficiency (urinary iodine <150 MUg/L) than the pregnant women with lower thiocyanate levels (OR = 3.882, 95 % CI 1.402-10.751, p = 0.009). Higher levels of urinary thiocyanate were found in women exposed to tobacco smoke, and quantification of these ions in urine provided a fast non-invasive method to monitor thiocyanate load. Due to the competitive inhibition of iodine intake by thiocyanates, their levels should be carefully monitored, especially in cases of severe iodine deficiency. PMID- 26676233 TI - Modelling mammography screening for breast cancer in the Canadian context: Modification and testing of a microsimulation model. AB - BACKGROUND: Modelling is a flexible and efficient approach to gaining insight into the trade-offs surrounding a complex process like breast screening, which involves more variables than can be controlled in an experimental study. DATA AND METHODS: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence and screening performance in Canada. The model considered effects of breast density on the sensitivity and specificity of screening. The model's ability to predict age-specific incidence of breast cancer was assessed. RESULTS: Predictions of age-adjusted incidence over calendar years and age-specific incidence of breast cancer in Canadian women are presented. Based on standard screening strategies, ratios of in situ to invasive disease and stage distribution of disease at diagnosis are compared with data from the British Columbia provincial screening program. INTERPRETATION: The adapted model performs well in predicting age-specific incidence and cross-sectional incidence in the absence of screening. The ratios of detection of in situ to invasive cancers and the overall stage distribution of detected cancers are in reasonable agreement with empirical data from British Columbia. PMID- 26676232 TI - Endosonography and magnetic resonance imaging in the diagnosis of high anal fistulae - a comparison. AB - Anal fistula is a benign inflammatory disease with unclear etiology which develops in approximately 10 in 100 000 adult patients. Surgical treatment of fistulae is associated with a risk of damaging anal sphincters. This usually happens in treating high fistulae, branched fistulae, and anterior ones in females. In preoperative diagnosis of anal fistulae, endosonography and magnetic resonance imaging play a significant role in planning the surgical technique. The majority of fistulae are diagnosed in endosonography, but magnetic resonance is performed when the presence of high fistulae, particularly branched ones, and recurrent is suspected. THE AIM OF THIS PAPER: The aim of this paper was to compare the roles of the two examinations in preoperative assessment of high anal fistulae. MATERIAL AND METHODS: The results of endosonographic and magnetic resonance examinations performed in 2011-2012 in 14 patients (4 women and 10 men) with high anal fistulae diagnosed intraoperatively were subject to a retrospective analysis. The patients were aged from 23 to 66 (mean 47). The endosonographic examinations were performed with the use of a BK Medical Pro Focus system with endorectal 3D transducers with the frequency of 16 MHz. The magnetic resonance scans were performed using a Siemens Avanto 1.5 T scanner with a surface coil in T1, T1FS, FLAIR, T2 sequences and in T1 following contrast medium administration. The sensitivity and specificity of endosonography and magnetic resonance imaging were analyzed. A surgical treatment served as a method for verification. The agreement of each method with the surgery and the agreement of endosonography and magnetic resonance imaging were compared in terms of the assessment of the fistula type, localization of its internal opening and branches. The agreement level was determined based on the percentage of consistent assessments and Cohen's coefficient of agreement, kappa. The integrity of the anal sphincters was assessed in each case. RESULTS: In determining the fistula type, magnetic resonance imaging agreed with intraoperative assessment in 79% of cases, and endosonography in 64% of cases. Endosonography agreed with magnetic resonance in 57% of cases. In the assessment of internal opening, the agreement between endosonography and intraoperative assessment was 65%, between magnetic resonance and intraoperative assessment - 41% and between endosonography and magnetic resonance - 53%. In the assessment of fistula branches, endosonography agreed with intraoperative assessment in 67% of cases, magnetic resonance in 87% of cases, and the agreement between the two methods tested was 67%. CONCLUSIONS: Magnetic resonance is a more accurate method than endosonography in determining the type of high fistulae and the presence of branches. In assessing the internal opening, endosonography proved more accurate. The agreement between the two methods ranges from 53-67%; the highest level of agreement was noted for the assessment of branching. PMID- 26676234 TI - Clinical outcomes of modelling mammography screening strategies. AB - BACKGROUND: A validated breast cancer model can be used to compare health outcomes associated with different screening strategies. DATA AND METHODS: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence, screening performance and delivery of optimal therapies in Canada. The model considered effects of breast density on incidence and screening performance. Model predictions of incidence, mortality and life-years (LY) gained for a 1960 birth cohort of women for No Screening were compared with 11 digital mammography screening strategies that varied by starting and stopping age and frequency. RESULTS: In the absence of screening, the estimate of LYs lost from breast cancer was 360.1 per 1,000 women, and each woman diagnosed with breast cancer after age 40 who dies of breast cancer would lose an average of 19.1 years. Biennial screening at ages 50 to 74 resulted in 116.3 LYs saved. Annual screening at ages 40 to 49, followed by biennial screening to age 74, resulted in 170.3 LY saved. Screening annually at ages 40 to 74 recovered the most: 214 LY saved. Annual screening at age 40 resulted in 54 LY gained per 1,000 women. More frequent screening was associated with an increased ratio of detection of ductal in situ to invasive cancers, more abnormal recalls and more negative biopsies, but a reduction in the number of women required to be screened per life saved or per LY saved. INTERPRETATION: In general, mortality reduction was found to be associated with the total number of lifetime screens for breast cancer. However, for the same number of screens, more frequent screening after age 50 appeared to have a greater impact than beginning screening earlier. When the number of LYs saved by screening was considered, a greater impact was achieved by screening women in their 40s than by reducing the interval between screens. PMID- 26676235 TI - Total cost-effectiveness of mammography screening strategies. AB - BACKGROUND: Breast cancer screening technology and treatment have improved over the past decade. This analysis evaluates the total cost-effectiveness of various breast cancer screening strategies in Canada. DATA AND METHODS: Using the Wisconsin Cancer Intervention and Surveillance Monitoring Network (CISNET) breast cancer simulation model adapted to the Canadian context, costs and quality adjusted life years (QALY) were evaluated for 11 mammography screening strategies that varied by start/stop age and screening frequency for the general population. Incremental cost-effectiveness ratios are presented, and sensitivity analyses are used to assess the robustness of model conclusions. RESULTS: Incremental cost effectiveness analysis showed that triennial screening at ages 50 to 69 was the most cost-effective at $94,762 per QALY. Biennial ($97,006 per QALY) and annual ($226,278 per QALY) strategies had higher incremental ratios. INTERPRETATION: The benefits and costs of screening rise with the number of screens per woman. Decisions about screening strategies may be influenced by willingness to pay and the rate of recall for further examination after positive screens. PMID- 26676236 TI - Multivariate analysis combined with GIS to source identification of heavy metals in soils around an abandoned industrial area, Eastern China. AB - Heavy metals in soils polluted by industrial production are a meaningful topic worldwide. The purpose of this study is to understand the pollution status and spatial distribution of heavy metals in soils. The result can help decision makers apportion possible soil heavy metals sources and formulate effective pollution control policies. In this paper, 155 soil samples (0-20 cm) were collected and analyzed for eight heavy metals (Cd, Hg, As, Cu, Pb, Cr, Zn, and Ni) from an abandoned industrial area of Tong County, located in Jiangsu Province of Eastern China. The multivariate analysis (including I(geo), Ei/RI, EF, PCA, and CA) and geostatistics (GIS) were used to assess the enrichment level and pollution level of soil heavy metals and identify their sources. The results indicated that eight heavy metals in soils had moderate variations, with CVs ranging from 19.63 to 63.34%. The pollution level of I(geo) of soil heavy metals decreased in the order of Cd~Zn > Cu > Hg~As~Pb~Cr~Ni. The enrichment level of soil heavy metals decreased in the order of Cd > Zn > Hg > Cu > Pb > Ni > As > Cr. According to the Ei, except Cd and Hg were in the significant and moderate ecological risk levels respectively, other soil heavy metals were in the clean or light ecological risk levels, the level of potential ecological risk (RI) of the whole industrial area was moderate. Finally, the source identification of soil heavy metals indicated that Cd and Zn were primarily controlled by human activities, and Hg and Cu were controlled by natural and anthropogenic sources, and As, Pb, Cr, and Ni were mainly controlled by soil parent materials. PMID- 26676237 TI - COI bingo. PMID- 26676238 TI - PRO-ONKO-selection of patient-reported outcome assessments for the clinical use in cancer patients-a mixed-method multicenter cross-sectional exploratory study. AB - PURPOSE: Cancer patients frequently suffer from multiple symptoms often impairing functional status and health-related quality of life (HRQOL). A comprehensive assessment including patient-reported outcomes (PROs) is recommended to enable individualized supportive care. However, PRO assessments are still not part of routine clinical practice. Therefore, this project aimed to compile an item pool from validated assessment instruments to facilitate the use of PROs for clinical decision-making in oncology clinics. METHODS: This qualitative dominant mixed method cross-sectional exploratory study was carried out in four centers and comprised two stages. Stage I: Six interdisciplinary focus groups were conducted to choose questionnaires meeting particular clinical requirements. Stage II: Adult patients with heterogeneous cancer diagnoses, receiving in- or out-patient treatment were asked to participate and complete the chosen questionnaires (participation 71/74). Resulting PROs were compared with clinical records. Health care professionals (HCPs) and patients rated the usefulness for routine clinical practice. RESULTS: The European Organisation of Research and Treatment of Cancer (EORTC) QLQ-C30 and Distress Thermometer were chosen for screening and M.D. Anderson Symptom Inventory (MDASI) and EORTC single items for monitoring. Comparison of n = 88 PRO assessments with clinical records showed consistent documentation of side effects like fever and emesis. Symptoms like fatigue, sadness, or sleep disturbance were not documented regularly in the medical records but captured by PRO assessments. Patients and HCPs judged the chosen questionnaires and electronic data collection as useful. CONCLUSIONS: Future studies should examine how PROs can complement or substitute routine documentation in order to achieve standardized assessment and documentation during the treatment process in different settings and examine possible benefits for patients. PMID- 26676239 TI - Psychological flexibility correlates with patient-reported outcomes independent of clinical or sociodemographic characteristics. AB - PURPOSE: The evidence for the effectiveness of psychological interventions for cancer patients is currently unclear. Acceptance and Commitment Therapy (ACT), which increases individual's levels of psychological flexibility, may be more effective than other frameworks of psychological intervention, but good quality research is needed to inform adoption and implementation. This study explored the correlation between psychological flexibility and patient-reported outcomes to assess the viability of this intervention for cancer survivors. METHODS: Recruitment was coordinated through a regional cancer centre. One hundred twenty nine respondents completed a cross-sectional postal questionnaire. They were of mixed gender, diagnosis and cancer stage; a mean 61 years old; and a mean 207 days post-diagnosis. Self-report questionnaires assessed psychological flexibility, mood, anxiety, depression, stress, quality of life and benefit finding. RESULTS: Psychological flexibility was a strong and consistent correlate of outcome; effects were maintained even when potentially confounding clinical and sociodemographic characteristics were controlled. CONCLUSIONS: Psychological flexibility can be modified through ACT-based interventions. Given the strong correlational evidence found in this study, it seems that such interventions might be useful for cancer survivors. High-quality and well-designed controlled trials are now needed to establish effectiveness. PMID- 26676240 TI - Assessment of volume status and fluid responsiveness in the emergency department: a systematic approach. AB - When treating acutely ill patients in the emergency department (ED), the successful management of a variety of medical conditions, such as sepsis, acute kidney injury, and pancreatitis, is highly dependent on the correct assessment and optimization of a patient's intravascular volume status. Therefore, it is crucial that the ED physician knows and uses available means to assess intravascular volume status to adequately guide fluid therapy. This review focuses on techniques for volume status assessment that are available in the ED including basic clinical and laboratory findings, apparatus-based tests such as sonography and chest x-ray, and functional tests to evaluate fluid responsiveness. Furthermore, we provide an outlook on promising innovative, noninvasive technologies that might be used for advanced hemodynamic monitoring in the ED. PMID- 26676241 TI - Effects of suckling duration on growth, slaughtering and carcass quality characteristics of Kivircik lambs. AB - Effects of suckling length (45, 75 and 120 days) and birth type (single and twin) on lamb growth, slaughtering and carcass quality characteristics were investigated using 40 Kivircik lambs. SC-45 and SC-75 lambs were weaned at 45 and 75 days of age, respectively, whilst SC-120 lambs remained with their mothers until the end of the experimental period. Lambs from all studied groups were slaughtered at 120 days of age. Weaning treatment caused a decrease in average daily gain in SC-45 and SC-75 lambs, and therefore, final weight was higher in SC 120 lambs than lambs from weaned groups. SC-120 lambs had higher empty body weight, cold carcass weight, dressing percentage, carcass measurements, carcass fatness (proportions of the kidney knob and channel fat, subcutaneous and intramuscular fat in pelvic limb) and non-carcass fatness (omental and mesenteric fat proportion) than weaned lambs. As a conclusion, the potential losses in meat production due to weaning should be considered before deciding the weaning of lambs at early ages. PMID- 26676242 TI - Intake and digestibility, rumen fermentation, and concentrations of metabolites in steers fed with peanut cake. AB - This study evaluated peanut cake as a replacement for soybean meal in the diet of steers. We used five castrated Holstein * Zebu steers, fistulated, with average live weight 550 kg, in a 5 * 5 Latin square design. The diets were composed of Tifton hay and ground corn with peanut cake (0, 25, 50, 75, and 100 %) as a replacement for soybean meal in the concentrate. Intake (kg/day) of dry matter, neutral detergent fiber, and crude protein were not affected by peanut cake, but ether extract intake increased linearly with the level of peanut cake in the diet. The digestibility of dry matter showed a quadratic effect, with a calculated maximum regression level of 56 % at 37 % replacement. There was no effect of the level of peanut cake on metabolizable energy intake and net energy, ammonia nitrogen, rumen pH, plasma urea, and glucose concentrations. We recommend replacing soybean meal in the concentrate with up to 40 % peanut cake. PMID- 26676243 TI - Risk analysis and seroprevalence of bovine ephemeral fever virus in cattle in the Kingdom of Saudi Arabia. AB - Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that causes disabling clinical signs and major economic losses in cattle and water buffalo. The disease is well documented in Asia, Africa, and the Middle East; however, the seroprevalence of BEFV in different regions and bovine breeds in the Kingdom of Saudi Arabia (KSA) is unknown. The aim of this study was to analyze risk factors which affect the prevalence of antibodies against BEFV in small herds of cattle in four geographical regions of KSA. A total of 1480 serum samples from non-BEFV vaccinated small herds of cattle were collected from the Eastern, Jizan, Qasim, and Riyadh regions (370 samples per region) during the summer of 2010. Serum neutralization test was used to detect antibodies against BEFV. There was a significant effect of region, breed, sex, and age on the seroprevalence of BEFV. Seropositive ratios were 18, 18, 26, and 12 % for the Eastern, Jizan, Qasim, and Riyadh regions, respectively (P = 0.00002); 23.2 % for dairy and 13.7 % for non dairy breeds (P = 0.00004); 24.4 % for males and 14.6 % for females (P = 0.00004); and 15.4, 29.1, and 11.4 % for animals <1 year, 1-3 years, and >3 years, respectively (P < 0.001). Risk analysis showed a significant effect of different regions of KSA on the seroprevalence of BEFV. Host risk factors (age, sex, and breed) showed also a significant effect on the seroprevalence of BEFV. This indicates active circulation of this virus in small herds of cattle. Insect control strategies and BEFV vaccination programs during the spring are recommended to reduce the spread of BEFV and minimize subsequent economic losses as this is adopted in many enzootic countries. PMID- 26676244 TI - Intake, performance, and carcass characteristics of lambs fed spineless cactus replacing wheat bran. AB - To assess the intake, digestibility of nutrients, ingestive behavior, performance, and carcass characteristics of feedlot lambs, 36 F1 Santa Ines * Dorper male lambs with an initial average weight of 19.5 +/- 0.27 kg were fed with different levels of spineless cactus (0, 33, 66, and 100 %) as a replacement of the wheat bran. The replacement diets had no effect on the intake of dry matter (DM) or crude protein (CP), whose average values were 962 and 140 g/day, respectively. There was a quadratic effect on the intake of digestible organic matter (OM) and the digestibility of DM, CP, neutral detergent fiber (NDF), and non-fiber carbohydrates (NFC). The highest average daily gain (ADG) of 168 g/day was achieved at 58.7 % replacement level. The highest hot and cold carcass weights of 15.4 and 14.5 kg were achieved at 62.4 and 56.9 % replacement levels. For lambs in the feedlot, we recommend replacing wheat bran with up to 58.7 % spineless cactus. PMID- 26676245 TI - The effect of male proximity on vaginal patency, estrous cycle length and feed intake of female grasscutters. AB - This study was conducted to investigate the influence of male proximity on vaginal patency, estrous cycle length and feed intake of nulliparous and pluriparous grasscutter (Thryonomys swinderianus) does. Twelve non-pregnant and non-lactating adult female (six nulliparous and six pluriparous) grasscutters and six proven male grasscutters were used for the study in a 2 * 2 factorial design. The factors were the type of contact between the sexes (no visual contact v. visual contact) and parity (nulliparous v. pluriparous). The condition of the vaginal membrane, which was monitored daily, was used as an indicator of the reproductive status of the experimental females. The findings of the study showed significant effect (P < 0.001) of male presence on feed intake. Visual contact between breeding pairs significantly (P < 0.05) increased the rate of vaginal opening (11 +/- 3.3 % v. 22 +/- 3.3 %) and significantly (P < 0.001) reduced the length of estrous cycling in the grasscutters (58 +/- 5 days v. 20 +/- 5 days). However, the duration of vaginal patency was not (P > 0.05) affected by the contact type. Parity had a significant (P < 0.05) effect on the duration of vaginal patency with pluriparous does recording longer duration compared to nulliparous does (76 +/- 12 h v. 38 +/- 12 h), but not on feed intake (P > 0.05). The study has revealed that housing breeding grasscutters such that females have visual contact with males could increase rate of vaginal patency and reduce the length of the estrous cycle in both pluriparous and nulliparous grasscutter does. This practice however compromises feed intake of the females. PMID- 26676246 TI - Social Support and Treatment Outcome in Alcohol Dependence Syndrome in Armed Forces. AB - INTRODUCTION: Social factors play vital role in unfolding of alcohol use disorders in any given population. Several factors beyond the confines of treatment settings influence treatment outcome in alcohol dependence syndrome. Social support has positive effect in treatment outcome of alcohol dependence syndrome. This has not been much studied in India in past. Therefore we decided to study the perception of social support in cases of alcohol dependence syndrome admitted in a busy hospital in armed forces. AIM: The aim was to study the perception of social support across relapsed and abstinent group and see if it reached any statistical proportion and also to see if any socio-demographic variables also affected perception of social support. MATERIALS AND METHODS: Fifty five consecutive male patients of alcohol dependent syndrome without a co morbid neurological/psychiatric diagnosis were assessed for their perception of social support after taking informed consent. They were explained the procedure and their alcoholic milestones were recorded in specially designed pro-forma. Subjects were then divided in abstinent and relapsed group. Subsequently they were assessed for their perception of social support by administering Social provision scale and Social support questionnaire. STATISTICAL ANALYSIS: Data were tabulated and statistically analysed by using chi square test, Mann Whitney U Test and Rank ANOVA test where applicable p-value <.05 was taken as significant. RESULTS: Results indicated that perception of social support across abstinent (n=18) and relapsed (n= 37) group reached significant statistical proportion as measured by social provision scale and social support questionnaire. Duration of use, dependence and family history of alcoholism did not influence perception of social support across patient population. There was inverse relationship between patients with alcohol related problem and their perception of social support. Professional and qualified soldiers perceived higher social support than soldiers and lesser qualified individuals. CONCLUSION: Abstinent group perceived better social support than relapsed group and soldiers in upper socio-occupational status and less alcohol related problems perceived more social support than soldiers with lower socioeconomic status and more alcohol related problems. Psychosocial therapy must be incorporated in management of Alcohol dependence syndrome. PMID- 26676247 TI - Tuberculosis treatment outcome in the European Union and European Economic Area: an analysis of surveillance data from 2002-2011. AB - Monitoring the treatment outcome (TO) of tuberculosis (TB) is essential to evaluate the effectiveness of the intervention and to identify potential barriers for TB control. The global target is to reach a treatment success rate (TSR) of at least 85%. We aimed to assess the TB TO in the European Union and European Economic Area (EU/EEA) between 2002 and 2011, and to identify factors associated with unsuccessful treatment. Only 18 countries reported information on TO for the whole observation period accounting for 250,854 new culture-confirmed pulmonary TB cases. The 85% target of TSR was not reached in any year between 2002 and 2011 and was on average 78%. The TSR for multidrug-resistant (MDR)-TB cases at 24 month follow-up was 49%. In the multivariable regression model, unsuccessful treatment was significantly associated with increasing age (odds ratio (OR) = 1.02 per a one-year increase, 95% confidence interval (CI): 1.02-1.02), MDR-TB (OR = 8.7, 95% CI: 5.09-14.97), male sex (OR = 1.40, 95% CI: 1.28-1.52), and foreign origin (OR = 1.32, 95% CI: 1.03-1.70). The data highlight that special efforts are required for patients with MDR-TB and the elderly aged >=65 years, who have particularly low TSR. To allow for valid monitoring at EU level all countries should aim to report TO for all TB cases. PMID- 26676249 TI - The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia. AB - Tolerance to central hypovolemia is highly variable, and accumulating evidence suggests that protection of anterior cerebral blood flow (CBF) is not an underlying mechanism. We hypothesized that individuals with high tolerance to central hypovolemia would exhibit protection of cerebral oxygenation (ScO2), and prolonged preservation of CBF in the posterior vs. anterior cerebral circulation. Eighteen subjects (7 male/11 female) completed a presyncope-limited lower body negative pressure (LBNP) protocol (3 mmHg/min onset rate). ScO2 (via near infrared spectroscopy), middle cerebral artery velocity (MCAv), posterior cerebral artery velocity (PCAv) (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Subjects who completed >=70 mmHg LBNP were classified as high tolerant (HT; n = 7) and low tolerant (LT; n = 11) if they completed <=60 mmHg LBNP. The minimum difference in LBNP tolerance between groups was 193 s (LT = 1,243 +/- 185 s vs. HT = 1,996 +/- 212 s; P < 0.001; Cohen's d = 3.8). Despite similar reductions in mean MCAv in both groups, ScO2 decreased in LT subjects from -15 mmHg LBNP (P = 0.002; Cohen's d=1.8), but was maintained at baseline values until -75 mmHg LBNP in HT subjects (P < 0.001; Cohen's d = 2.2); ScO2 was lower at -30 and -45 mmHg LBNP in LT subjects (P <= 0.02; Cohen's d >= 1.1). Similarly, mean PCAv decreased below baseline from -30 mmHg LBNP in LT subjects (P = 0.004; Cohen's d = 1.0), but remained unchanged from baseline in HT subjects until -75 mmHg (P = 0.006; Cohen's d = 2.0); PCAv was lower at -30 and -45 mmHg LBNP in LT subjects (P <= 0.01; Cohen's d >= 0.94). Individuals with higher tolerance to central hypovolemia exhibit prolonged preservation of CBF in the posterior cerebral circulation and sustained cerebral tissue oxygenation, both associated with a delay in the onset of presyncope. PMID- 26676248 TI - Hypoxemia, oxygen content, and the regulation of cerebral blood flow. AB - This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2 ) rather than arterial O2 tension (PaO2 ) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2 . We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2 ) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered. PMID- 26676251 TI - Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation. AB - Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [(14)C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [(14)C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [(14)C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID- 26676254 TI - Treatment of Virgin OHVIRA Syndrome with Haematometrocolpos by Complete Incision of Vaginal Septum without Hymenotomy. AB - Mullerian malformations result from defective fusion of the Mullerian ducts during development of the female reproductive system and have an incidence of 2 3%. The American Fertility Society classification of Mullerian anomalies is the most commonly utilized standardized classification. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). This syndrome has been described with case reports since 1922. Early diagnosis and surgery that include drainage of fluid and resection of the vaginal septum is necessary for OHVIRA to prevent late complications (i.e. pyocolpos, chronic cryptomenorrhea). Here in we report a case of Herlyn-Werner-Wunderlich syndrome that hymen has been preserved during the operation of non-fenestrated transverse vaginal septum resection with hysteroscopy. PMID- 26676252 TI - Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity. AB - Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80-90% in 4-wk-old male DR rats reduced their ARC and VMN (125)I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity. PMID- 26676253 TI - Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats. AB - This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under alpha chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective beta-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P < 0.05) reduced the amplitude and area under the curve of the bladder contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a beta-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders. PMID- 26676250 TI - Vitamin D supplementation improves pathophysiology in a rat model of preeclampsia. AB - Deficiency of vitamin D (VD) is associated with preeclampsia (PE), a hypertensive disorder of pregnancy characterized by proinflammatory immune activation. We sought to determine whether VD supplementation would reduce the pathophysiology and hypertension associated with the reduced uterine perfusion pressure (RUPP) rat model of PE. Normal pregnant (NP) and RUPP rats were supplemented with VD2 or VD3 (270 IU and 15 IU/day, respectively) on gestation days 14-18 and mean arterial pressures (MAPs) measured on day 19. MAP increased in RUPP to 123 +/- 2 mmHg compared with 102 +/- 3 mmHg in NP and decreased to 113 +/- 3 mmHg with VD2 and 115 +/- 3 mmHg with VD3 in RUPP rats. Circulating CD4+ T cells increased in RUPP to 7.90 +/- 1.36% lymphocytes compared with 2.04 +/- 0.67% in NP but was lowered to 0.90 +/- 0.19% with VD2 and 4.26 +/- 1.55% with VD3 in RUPP rats. AT1 AA, measured by chronotropic assay, decreased from 19.5 +/- 0.4 bpm in RUPPs to 8.3 +/- 0.5 bpm with VD2 and to 15.4 +/- 0.7 bpm with VD3. Renal cortex endothelin-1 (ET-1) expression was increased in RUPP rats (11.6 +/- 2.1-fold change from NP) and decreased with both VD2 (3.3 +/- 1.1-fold) and VD3 (3.1 +/- 0.6-fold) supplementation in RUPP rats. Plasma-soluble FMS-like tyrosine kinase-1 (sFlt-1) was also reduced to 74.2 +/- 6.6 pg/ml in VD2-treated and 91.0 +/- 16.1 pg/ml in VD3-treated RUPP rats compared with 132.7 +/- 19.9 pg/ml in RUPP rats. VD treatment reduced CD4+ T cells, AT1-AA, ET-1, sFlt-1, and blood pressure in the RUPP rat model of PE and could be an avenue to improve treatment of hypertension in response to placental ischemia. PMID- 26676255 TI - Ester Cross-Link Profiling of the Cutin Polymer of Wild-Type and Cutin Synthase Tomato Mutants Highlights Different Mechanisms of Polymerization. AB - Cuticle function is closely related to the structure of the cutin polymer. However, the structure and formation of this hydrophobic polyester of glycerol and hydroxy/epoxy fatty acids has not been fully resolved. An apoplastic GDSL lipase known as CUTIN SYNTHASE1 (CUS1) is required for cutin deposition in tomato (Solanum lycopersicum) fruit exocarp. In vitro, CUS1 catalyzes the self transesterification of 2-monoacylglycerol of 9(10),16-dihydroxyhexadecanoic acid, the major tomato cutin monomer. This reaction releases glycerol and leads to the formation of oligomers with the secondary hydroxyl group remaining nonesterified. To check this mechanism in planta, a benzyl etherification of nonesterified hydroxyl groups of glycerol and hydroxy fatty acids was performed within cutin. Remarkably, in addition to a significant decrease in cutin deposition, mid-chain hydroxyl esterification of the dihydroxyhexadecanoic acid was affected in tomato RNA interference and ethyl methanesulfonate-cus1 mutants. Furthermore, in these mutants, the esterification of both sn-1,3 and sn-2 positions of glycerol was impacted, and their cutin contained a higher molar glycerol-to dihydroxyhexadecanoic acid ratio. Therefore, in planta, CUS1 can catalyze the esterification of both primary and secondary alcohol groups of cutin monomers, and another enzymatic or nonenzymatic mechanism of polymerization may coexist with CUS1-catalyzed polymerization. This mechanism is poorly efficient with secondary alcohol groups and produces polyesters with lower molecular size. Confocal Raman imaging of benzyl etherified cutins showed that the polymerization is heterogenous at the fruit surface. Finally, by comparing tomato mutants either affected or not in cutin polymerization, we concluded that the level of cutin cross-linking had no significant impact on water permeance. PMID- 26676257 TI - Impact of cation-pi interactions on the cell voltage of carbon nanotube-based Li batteries. AB - Carbon nanotube (CNT)-based Li batteries have attracted wide attention because of their high capacity, high cyclability and high energy density and are believed to be one of the most promising electrochemical energy storage systems. In CNT-based Li batteries, the main interaction between the Li(+) ions and the CNT is the cation-pi interaction. However, up to now, it is still not clear how this interaction affects the storage characteristics of CNT-based Li batteries. Here, using density functional theory (DFT) calculations, we report a highly favorable impact of cation-pi interactions on the cell voltage of CNT-based Li batteries. Considering both Li(+)-pi interaction and Li-pi interaction, we show that cell voltage enhances with the increase of the CNT diameter. In addition, when the Li(+) ion adsorbs on the external wall, the cell voltage is larger than that when it adsorbs on the internal wall. This suggests that CNTs with a large diameter and a low array density are more advantageous to enhance storage performance of CNT-based Li batteries. Compared with Li(+) ions on the (4,4) CNT internal wall, the cell voltage of Li(+) on the (10,10) CNT external wall is 0.55 V higher, which indicates an improvement of about 38%. These results will be helpful for the design of more efficient CNT-based Li batteries. PMID- 26676256 TI - Chloroplast Hsp93 Directly Binds to Transit Peptides at an Early Stage of the Preprotein Import Process. AB - Three stromal chaperone ATPases, cpHsc70, Hsp90C, and Hsp93, are present in the chloroplast translocon, but none has been shown to directly bind preproteins in vivo during import, so it remains unclear whether any function as a preprotein translocating motor and whether they have different functions during the import process. Here, using protein crosslinking followed by ionic detergent solubilization, we show that Hsp93 directly binds to the transit peptides of various preproteins undergoing active import into chloroplasts. Hsp93 also binds to the mature region of a preprotein. A time course study of import, followed by coimmunoprecipitation experiments, confirmed that Hsp93 is present in the same complexes as preproteins at an early stage when preproteins are being processed to the mature size. In contrast, cpHsc70 is present in the same complexes as preproteins at both the early stage and a later stage after the transit peptide has been removed, suggesting that cpHsc70, but not Hsp93, is important in translocating processed mature proteins across the envelope. PMID- 26676258 TI - Elective ventilation to facilitate organ donation in infants with anencephaly: perinatal professionals' views and an ethical analysis. AB - AIM: Following the elective ventilation and referral for organ donation of an infant with anencephaly, we sought local perinatal professionals' views of this practice. METHODS: Anonymous online survey: demographics, ethical viewpoints and potential public/maternal perceptions (standard 5-part Likert scale and free text). RESULTS: DEMOGRAPHICS: 49 replies (38 female): 4 obstetricians, 14 neonatologists, 6 foetal clinicians, 23 nurses, 1 anaesthetist and 1 reproductive specialist. EXPERIENCE: 0.5-33 years (average 12). Twenty-one had experience of anencephalic delivery, and 10 reported pregnancy continued for religious reasons. ETHICS: (i) 73% thought anencephalic donation acceptable, of which 64% supported elective ventilation, 20% neutral and 16% disagreed. (ii) Provision of treatments not in infant's strict best interest to facilitate donation: 22% strongly agreed, 36% agreed, 33% neutral and 9% disagreed. (iii) Accept ventilation to permit donation if societal benefit: 53% agreed, 33% neutral and 13% disagreed. (iv) Public opinion: 59% disagreed anencephalic donation would harm public opinion about donation and 19% agreed. CONCLUSION: We found a supportive local environment for donation in the setting of anencephaly, including support for elective ventilation. Given this, and our ethical analysis, we recommend provision of organ donation information as part of palliative care counselling for women carrying a foetus with a condition likely to be fatal in infancy. PMID- 26676260 TI - An optimized, fast-to-perform mouse lung infection model with the human pathogen Chlamydia trachomatis for in vivo screening of antibiotics, vaccine candidates and modified host-pathogen interactions. AB - Chlamydia trachomatis causes sexually transmitted diseases with infertility, pelvic inflammatory disease and neonatal pneumonia as complications. The duration of urogenital mouse models with the strict mouse pathogen C. muridarum addressing vaginal shedding, pathological changes of the upper genital tract or infertility is rather long. Moreover, vaginal C. trachomatis application usually does not lead to the complications feared in women. A fast-to-perform mouse model is urgently needed to analyze new antibiotics, vaccine candidates, immune responses (in gene knockout animals) or mutants of C. trachomatis. To complement the valuable urogenital model with a much faster and quantifiable screening method, we established an optimized lung infection model for the human intracellular bacterium C. trachomatis serovar D (and L2) in immunocompetent C57BL/6J mice. We demonstrated its usefulness by sensitive determination of antibiotic effects characterizing advantages and limitations achievable by early or delayed short tetracycline treatment and single-dose azithromycin application. Moreover, we achieved partial acquired protection in reinfection with serovar D indicating usability for vaccine studies, and showed a different course of disease in absence of complement factor C3. Sensitive monitoring parameters were survival rate, body weight, clinical score, bacterial load, histological score, the granulocyte marker myeloperoxidase, IFN-gamma, TNF-alpha, MCP-1 and IL-6. PMID- 26676261 TI - Serum metabolomics analysis of rat after intragastric infusion of Pu-erh theabrownin. AB - BACKGROUND: The aim was to study the effects of Pu-erh theabrownin (TB) (Mw > 50 kDa) on the metabolism of rat serum by nuclear magnetic resonance (NMR)-based metabolomics and identify candidate marker metabolites associated with Pu-erh TB, and thus provide fundamental information for a better understanding of the metabolism of Pu-erh tea in animals. RESULTS: TB infusion induced different changes in endogenous serum metabolites depending on the type of diet. Compared with the control group, the TB infusion group showed significantly reduced serum glycine and choline levels, as well as significantly increased taurine, carnitine and high-density lipoprotein (all P < 0.05). Compared with the high-lipid group, the high-lipid TB infusion group exhibited significantly reduced low-density lipoprotein and acetate levels, as well as significantly increased inositol, carnitine and glycine levels (all P < 0.05). CONCLUSION: Examination of the variations of these differential expressed metabolites and their individual functions revealed that the TB extract accelerated lipid catabolism in rats and might affect glucose metabolism. Of these, carnitine level significantly increased after intragastric infusion of TB regardless of the type of diet, and activities of carnitine palmitoyltransferases I and II changed significantly, suggesting carnitine may be a candidate serum marker for tracking the metabolism of TB in rats. (c) 2015 Society of Chemical Industry. PMID- 26676266 TI - CD147 overexpression promotes tumorigenicity in Chinese hamster ovary cells. AB - CD147 overexpresses in many epithelium-originated tumors and plays an important role in tumor migration and invasion. Most studies aim at the role of CD147 in tumor progression using tumor cell models. However, the influence of abnormal overexpression of CD147 on neoplastic transformation of normal cells is unknown. Here, the role of CD147 in malignant phenotype transformation in CHO cells was investigated. Three CHO cell lines that stably overexpressed CD147 (CHO-CD147), EGFP-CD147 (CHO-EGFP-CD147), and EGFP (CHO-EGFP) were generated by transfection of plasmids containing human CD147, EGFP-human CD147, and EGFP genes into CHO cells. Cell migration and invasion were detected by wound healing and transwell matrix penetration assay. Trypan blue exclusion, MTT, cell cycle analysis, and BrdU cell proliferation assay were used to detect cell viability and cell proliferation. Annexin V-FITC analysis was performed to detect apoptosis. We found that CD147 overexpression promoted the migration and invasion of CHO cells. CD147 accelerated the G1 to S phase transition and enhanced the CHO cell proliferation. Overexpression of CD147 inhibited both early- and late-stages of apoptosis of CHO-CD147 cells, which is caused by serum deprivation. CHO-EGFP CD147 cells showed an increased anchorage-independent growth compared with CHO EGFP cells as detected by soft-agar colony formation assay. The tumors formed by CHO-CD147 cells in nude mice were larger and coupled with higher expression of proliferating cell nuclear antigen and Ki-67 than that of CHO cells. In conclusion, human CD147 overexpression induces malignant phenotype in CHO cells. PMID- 26676267 TI - Obstetric complications and mother's age at delivery are predictors of eating disorder symptoms among Health Science college students. AB - OBJECTIVE: To identify the association between perinatal/neonatal factors and symptoms of eating disorders among college students. METHODS: Four hundred and eight college students (283 women), aged 18 to 23 years old, enrolled in the first semester of a Bachelor of Health Science degree program were included in the sample. Eating disorder symptoms and body image dissatisfaction were assessed with the Eating Attitudes Test and Bulimic Investigatory Test of Edinburgh. Information regarding birth weight, breastfeeding, obstetric complications, mother's age at delivery, type of delivery, and birth order were self-reported by the volunteers after consulting their parents. Association between perinatal and neonatal factors and symptoms of anorexia nervosa and bulimia nervosa were assessed by binary logistic regression adjusted for sex, age, and body mass index. RESULTS: The likelihood of presenting with symptoms of anorexia nervosa was 0.5 time lower for those students born from the oldest mothers (odds ratio - OR=0.37; 95% confidence interval - 95%CI: 0.17-0.83). Relative to bulimia nervosa, the risk was higher among students who reported obstetric complications (OR=2.62; 95%CI: 1.03-6.67). CONCLUSION: We observed the association between perinatal and neonatal factors with symptoms of eating disorders in college students. PMID- 26676268 TI - Impact of telemedicine in hospital culture and its consequences on quality of care and safety. AB - OBJECTIVE: To describe the impact of the telemedicine application on the clinical process of care and its different effects on hospital culture and healthcare practice. METHODS: The concept of telemedicine through real time audio-visual coverage was implemented at two different hospitals in Sao Paulo: a secondary and public hospital, Hospital Municipal Dr. Moyses Deutsch, and a tertiary and private hospital, Hospital Israelita Albert Einstein. RESULTS: Data were obtained from 257 teleconsultations records over a 12-month period and were compared to a similar period before telemedicine implementation. For 18 patients (7.1%) telemedicine consultation influenced in diagnosis conclusion, and for 239 patients (92.9%), the consultation contributed to clinical management. After telemedicine implementation, stroke thrombolysis protocol was applied in 11% of ischemic stroke patients. Telemedicine approach reduced the need to transfer the patient to another hospital in 25.9% regarding neurological evaluation. Sepsis protocol were adopted and lead to a 30.4% reduction mortality regarding severe sepsis. CONCLUSION: The application is associated with differences in the use of health services: emergency transfers, mortality, implementation of protocols and patient management decisions, especially regarding thrombolysis. These results highlight the role of telemedicine as a vector for transformation of hospital culture impacting on the safety and quality of care. PMID- 26676269 TI - Clinical features and overall survival among elderly cancer patients in a tertiary cancer center. AB - OBJECTIVE: To evaluate the epidemiological profile and overall survival of a large population of elderly individuals diagnosed with solid tumors in a tertiary hospital. METHODS: This retrospective study included patients aged >65 years, diagnosed with solid tumors between January 2007 and December 2011, at Hospital Israelita Albert Einstein, Sao Paulo, Brazil. The medical records were reviewed to obtain information about clinical variables and overall survival. RESULTS: A total of 806 patients were identified, and 58.4% were male. Mean age was 74 years (65 to 99 years). The most common types were prostate (22%), colorectal (21%), breast (19%), and lung cancer (13%), followed by bladder (8%), pancreas (6%), and other types (11%). The majority of patients were diagnosed at early stage disease. After a median follow-up of 27 months (15 to 45 months), 29% of the patients (234/806) died, predominantly in the group older than 70 years. For the entire cohort, the median 2-year survival rate was 71%. Median overall survival was not reached within the study period. In a multivariate analysis, age (HR: 1.35; 95%CI: 1.25-1.45; p<0.001) and disease stage (HR: 1.93; 95%CI: 1.75-2.14; p<0.001) were independent negative predictors of poor survival. CONCLUSION: The most prevalent tumors were prostate, colorectal, breast, and lung cancer, with the larger proportion diagnosed at initial stages, reflecting the great number of patients alive at last follow-up. PMID- 26676272 TI - Exceptional Exercise Capacity in an 80-Year-Old Breast Cancer Survivor and Long Term Sprint Athlete. PMID- 26676270 TI - Behavioral and electrophysiological auditory processing measures in traumatic brain injury after acoustically controlled auditory training: a long-term study. AB - OBJECTIVE: To investigate the long-term efficacy of acoustically controlled auditory training in adults after tarumatic brain injury. METHODS: A total of six audioogically normal individuals aged between 20 and 37 years were studied. They suffered severe traumatic brain injury with diffuse axional lesion and underwent an acoustically controlled auditory training program approximately one year before. The results obtained in the behavioral and electrophysiological evaluation of auditory processing immediately after acoustically controlled auditory training were compared to reassessment findings, one year later. RESULTS: Quantitative analysis of auditory brainsteim response showed increased absolute latency of all waves and interpeak intervals, bilaterraly, when comparing both evaluations. Moreover, increased amplitude of all waves, and the wave V amplitude was statistically significant for the right ear, and wave III for the left ear. As to P3, decreased latency and increased amplitude were found for both ears in reassessment. The previous and current behavioral assessment showed similar results, except for the staggered spondaic words in the left ear and the amount of errors on the dichotic consonant-vowel test. CONCLUSION: The acoustically controlled auditory training was effective in the long run, since better latency and amplitude results were observed in the electrophysiological evaluation, in addition to stability of behavioral measures after one-year training. PMID- 26676271 TI - Most small bowel cancers are revealed by a complication. AB - OBJECTIVE: To characterize the pattern of primary small bowel cancers in a tertiary East-European hospital. METHODS: A retrospective study of patients with small bowel cancers admitted to a tertiary emergency center, over the past 15 years. RESULTS: There were 57 patients with small bowel cancer, representing 0.039% of admissions and 0.059% of laparotomies. There were 37 (64.9%) men, mean age of 58 years; and 72 years for females. Out of 57 patients, 48 (84.2%) were admitted due to an emergency situation: obstruction in 21 (38.9%), perforation in 17 (31.5%), upper gastrointestinal bleeding in 8 (14.8%), and lower gastrointestinal bleeding in 2 (3.7%). There were 10 (17.5%) duodenal tumors, 21 (36.8%) jejunal tumors and 26 (45.6%) ileal tumors. The most frequent neoplasms were gastrointestinal stromal tumor in 24 patients (42.1%), adenocarcinoma in 19 (33.3%), lymphoma in 8 (14%), and carcinoids in 2 (3.5%). The prevalence of duodenal adenocarcinoma was 14.55 times greater than that of the small bowel, and the prevalence of duodenal stromal tumors was 1.818 time greater than that of the small bowel. Obstruction was the complication in adenocarcinoma in 57.9% of cases, and perforation was the major local complication (47.8%) in stromal tumors. CONCLUSION: Primary small bowel cancers are usually diagnosed at advanced stages, and revealed by a local complication of the tumor. Their surgical management in emergency setting is associated to significant morbidity and mortality rates. PMID- 26676273 TI - The Esthetic Effect of Veneered Zirconia Abutments for Single-Tooth Implant Reconstructions: A Randomized Controlled Clinical Trial. AB - PURPOSE: The purposes of this study were to test whether or not veneering of the submucosal part of zirconia abutments can positively influence the esthetic outcome compared with nonveneered zirconia abutments; to evaluate the influence of the mucosal thickness on the esthetic outcomes of the veneered and nonveneered abutments; and to evaluate the thickness of the peri-implant mucosa compared with the thickness of the gingiva of contralateral tooth sites. MATERIALS AND METHODS: Forty-four single-tooth implants in 44 patients were randomly restored with either cemented (CR) or screw-retained (SR) reconstructions based on white zirconia abutments (CR-W, SR-W) or pink-veneered zirconia abutments (CR-P, SR-P). Esthetic outcome measurements were performed based on a spectrophotometric evaluation of the peri-implant mucosal color. In addition, the thickness of the mucosa was measured. A two-way analysis of variance was conducted to test the effect of veneering (pink vs white) and mucosa thickness (<2 mm vs >=2 mm) on the calculated color difference DeltaE for pooled data of CR and SR reconstructions (p < .05). RESULTS: Analyses grouping the sites according to veneering of the abutments and mucosal thickness demonstrated less discoloration for sites with a veneered abutment irrespective of the mucosal thickness: DeltaE 4.50 +/- 1.93 (<2 mm) and DeltaE 6.88 +/- 2.45 (>=2 mm); CR-P, SR-P) compared with sites without veneering DeltaE 9.72 +/- 3.82 (<2 mm; CR-W, SR-W) and DeltaE 8.31 +/- 2.98 (>=2 mm). The differences between veneered and nonveneered abutments were significant (p = .032). CONCLUSIONS: Veneering of zirconia abutments with pink veneering ceramic positively influenced the peri-implant mucosal color. PMID- 26676274 TI - Molecular cloning and functional characterization of murine toll-like receptor 8. AB - Toll-like receptors (TLRs) are a large family of germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns and evoke the relevant innate immune responses. TLR8 is a member of several endosome nucleic acid-sensing TLRs; however little attention has been paid to murine TLR8 (mTLR8) compared with other endosome nucleic acid-sensing TLRs. In the present study, mTLR8 was cloned using reverse transcription polymerase chain reaction from murine peripheral blood mononuclear cells and its function in regulating innate immune response was characterized. The open reading frame of mTLR8 consists of 3,099 bps and encodes 1,032 amino acids. It contains typical leucine-rich repeats, a transmembrane domain and a Toll/interleukin-1 receptor domain, and it shares a high level of identity with other mammalian species. The expression of mTLR8 has been widely observed in different tissues, and higher expression levels of mTLR8 have mainly been detected in the heart, spleen and lung. Overexpression of mTLR8 is required for the activation of transcription factor nuclear factor-kappaB and the production of tumor necrosis factor-alpha. However, mTLR8 is not able to activate interferon regulatory factor 3 or activator protein 1, nor can it induce interferon-alpha in HEK293T cells. These results indicate that mTLR8, as an important PRR, is indeed functional and is vital role in the activation of innate immune responses. This study may aid in determining the molecular basis of the interactions between mTLR8 and pathogens. PMID- 26676275 TI - A Calculating Device to Predict Individualized Outcomes in Adrenocortical Carcinoma. PMID- 26676276 TI - PREVALENCE OF MUSCULOSKELETAL PAIN AMONG SWIMMERS IN AN ELITE NATIONAL TOURNAMENT. AB - BACKGROUND: Professional swimmers are often affected by a high number of injuries due to their large amount of training. The occurrence of musculoskeletal pain during an important tournament has not been investigated. OBJECTIVE: The objective of the study was to assess the prevalence of musculoskeletal pain and its characteristics in professional swimmers. Secondary objectives included evaluating the swimmers' injury history over the previous 12 months, and examining the association of the presence of pain with personal and training characteristics of the swimmers. DESIGN: Observational, cross-sectional study. METHOD: Two-hundred and fifty-seven swimmers who participated in the Brazilian Swimming Championship were included in the study and answered a questionnaire about personal and training characteristics, presence of pain, and injuries in the previous 12 months. The relative risk of presence of pain was calculated for the following variables: gender, BMI, stroke specialty, swimmer's position, strength training, practice of another physical activity, and previous injuries. RESULTS: The prevalence of musculoskeletal pain was about 20%, with 60% of swimmers reporting at least one injury in the previous 12 months. The shoulder was the most commonly affected region and tendinopathy was the most common type of previous injury. No significant relationships were found between the presence of pain and personal or training characteristics. CONCLUSIONS: The results demonstrated that the prevalence of musculoskeletal pain in professional swimmers participating in the most important Brazilian national tournament was approximately 20%, while the majority of participants reported previous injuries in many areas. LEVEL OF EVIDENCE: 2c. PMID- 26676277 TI - The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients. AB - BACKGROUND: Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. OBJECTIVES: The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. MATERIALS AND METHODS: In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. RESULTS: Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients' categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). CONCLUSION: Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID- 26676279 TI - Home blood pressure monitoring and self-titration of antihypertensive medications: Proposed patient selection criteria. AB - BACKGROUND AND PURPOSE: Recent studies have demonstrated that home blood pressure monitoring (HBPM), coupled with self-titration of medications is a viable intervention to control hypertension. There are currently no established criteria to evaluate patients for inclusion in such a program. The purpose of this discussion is to propose criteria for determining if a patient is appropriate to participate in a program of HBPM and self-titration. METHODS: Inclusion criteria for two self-titration trials were examined, and additional factors in clinical practice were identified and discussed. Additional selection criteria were proposed to support the decision to enroll a patient in an antihypertensive self titration program. CONCLUSIONS: Inclusion criteria from self-titration trials provide a reasonable starting point for choosing appropriate patients in clinical practice, but additional research is necessary. Adaptation of these criteria and consideration of the identified factors can be used to develop decision support instruments. Such instruments should be evaluated for effectiveness and reliability prior to use in clinical practice. IMPLICATIONS FOR PRACTICE: HBPM combined with self-titration is an effective patient-centered approach for hypertension management. Decision support instruments to determine appropriate patients are necessary for safe and effective use in clinical practice. PMID- 26676278 TI - Methodology for developing competency standards for dietitians in Australia. AB - Competency standards document the knowledge, skills, and attitudes required for competent performance. This study develops competency standards for dietitians in order to substantiate an approach to competency standard development. Focus groups explored the current and emerging purpose, role, and function of the profession, which were used to draft competency standards. Consensus was then sought using two rounds of a Delphi survey. Seven focus groups were conducted with 28 participants (15 employers/practitioners, 5 academics, 8 new graduates). Eighty-two of 110 invited experts participated in round one and 67 experts completed round two. Four major functions of dietitians were identified: being a professional, influencing the health of individuals, groups, communities, and populations through evidence-based nutrition practice, and working collaboratively in teams. Overall there was a high level of consensus on the standards: 93% achieved agreement by participants in round one and all revised standards achieved consensus on round 2. The methodology provides a framework for other professions wishing to embark on competency standard review or development. PMID- 26676280 TI - Prenatal Exposure to BPA and Offspring Outcomes: The Diabesogenic Behavior of BPA. AB - Obesity and type 2 diabetes mellitus (T2DM) are the most common metabolic disorders, with prevalence rates that are reaching epidemic proportions. Both are complex conditions affecting virtually all ages and with serious health consequences. The underlying cause of the problem is still puzzling, but both genetic and environmental factors including unhealthy diet, sedentary lifestyle, or the exposure to some environmental endocrine disrupting chemicals (EDCs) are thought to have a causal influence. In addition, the impact of early environment has recently emerged as an important factor responsible for the increased propensity to develop adult-onset metabolic disease. Suboptimal maternal nutrition during critical windows in fetal development is the most commonly studied factor affecting early programming of obesity and T2DM. In recent years, increasing experimental evidence shows that exposure to EDCs could also account for this phenomenon. In the present review, we will overview the most relevant findings that confirm the critical role of bisphenol-A, one of the most widespread EDCs, in the development of metabolic disorders. PMID- 26676282 TI - Is Single-Radius Design Better for Quadriceps Recovery in Total Knee Arthroplasty? AB - PURPOSE: Although single-radius (SR) designs have a theoretical advantage in quadriceps recovery following total knee arthroplasty (TKA), there has been a paucity of objective evaluation studies. MATERIALS AND METHODS: One hundred and twenty minimally invasive TKAs were prospectively randomized by a single surgeon into 2 groups: SR design TKA group and multi-radius design TKA group. Quadriceps force and power were assessed using a dynamometer, and clinical data were investigated preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. RESULTS: There were no differences between two groups in quadriceps recovery and clinical results throughout the follow-up period. Furthermore, the proportion of patients whose postoperative quadriceps force and power reached preoperative level was similar in both groups. CONCLUSIONS: Femoral component design itself would not significantly influence quadriceps recovery after TKA. PMID- 26676283 TI - Facile and Efficient Synthesis of Carbosiloxane Dendrimers via Orthogonal Click Chemistry Between Thiol and Ene. AB - A combination of a thiol-Michael addition reaction and a free radical mediated thiol-ene reaction is employed as a facile and efficient approach to carbosiloxane dendrimer synthesis. For the first time, carbosiloxane dendrimers are constructed rapidly by an orthogonal click strategy without protection/deprotection procedures. The chemoselectivity of these two thiol-ene click reactions leads to a design of a new monomer containing both electron deficient carbon-carbon double bonds and unconjugated carbon-carbon double bonds. Siloxane bonds are introduced as the linker between these two kinds of carbon carbon double bonds. Starting from a bifunctional thiol core, the dendrimers are constructed by iterative thiol-ene click reactions under different but both mild reaction conditions. After simple purification steps the fifth dendrimer with 54 peripheral functional groups is obtained with an excellent overall yield in a single day. Furthermore, a strong blue glow is observed when the dendrimer is excited by a UV lamp. PMID- 26676281 TI - Effects of Ligustrum robustum on gut microbes and obesity in rats. AB - AIM: To investigate the anti-obesity and antibacterial effects of Ligustrum robustum (L. robustum) in vivo and in vitro and its possible mechanisms. METHODS: The effects of L. robustum aqueous extract (LR) on various gut bacteria in vitro were evaluated. The effects of LR on high-fat diet-fed (HFD) rats in vivo were also assessed. Culture methods, quantitative polymerase chain reaction, and terminal-restriction fragment length polymorphism were used to analyze the effects of LR on gut bacteria. Biochemical tests were also performed to detect the changes in obesity-related indicators after LR treatment. RESULTS: LR treatment lowered adipose weight and decreased Lee's index, blood glucose, total cholesterol, and lipid in the tested groups relative to control (P < 0.05). To determine the reasons for these changes, we assessed the potential bacteriostatic and bactericidal effects of LR on specific bacterial species in vitro. LR affected the richness, diversity, and evenness of gut bacteria, increased fecal Lactobacillus, and decreased Enterococci in HFD rats (P < 0.05). CONCLUSION: L. robustum may be a safe and effective food for weight loss and obesity control, and the effects of L. robustum might be mediated by the regulation of gut bacteria. PMID- 26676284 TI - Sensor Mechanism and Afferent Signal Transduction of the Urinary Bladder: Special Focus on transient receptor potential Ion Channels. AB - In the urine storage phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter Adelta- and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous; however, a wide range of ion channels (e.g. TTX resistant Na(+) channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes: TRPV (Vanilloid), TRPC (Canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction. PMID- 26676285 TI - Management of Low Compliant Bladder in Spinal Cord Injured Patients. AB - Low bladder compliance means an abnormal volume and pressure relationship, and an incremental rise in bladder pressure during the bladder filling. It is well known that at the time bladder capacity decreases, intravesical pressure increases, and the risk of upper deterioration increases. Hypocompliance is usually thought to be the range from 1.0 to 20.0 mL/cmH2 O. Though the exact cause of hypocompliance is not known, it may be caused by changes in the elastic and viscoelastic properties of the bladder, changes in detrusor muscle tone, or combinations of the two. Management aims at increasing bladder capacity with low intravesical pressure. The main is a medical therapy with antimuscarinics combined with clean intermittent catheterization. The results are sometimes unsatisfactory. Various drugs or agents through the mouth or the bladder, including oxybutynin, new antimuscarinics, capsaicin and resiniferatoxin were tried. Among them botulinum toxin-A is promising. Some patients eventually required surgical intervention in spite of the aggressive medical therapy. Finally most patients undergo the surgical treatment including autoaugmentation, diversion, and augmentation cystoplasty. Among them augmentation cystoplasty still seems the only clearly verified treatment method. PMID- 26676286 TI - Effect of Partial Bladder Outlet Obstruction on the Morphology of Elastin in Rabbit Bladder Smooth Muscle. AB - OBJECTIVES: Elastin, in association with collagen, allows the body's organs to stretch and relax. Collagen and elastin, the major components of connective tissue, are present throughout the bladder wall and are intimately related to bladder compliance. The present study was undertaken to evaluate elastin morphologically using immunostaining and electron microscopy in the rabbit model of partial bladder outlet obstruction (PBOO). METHODS: Four groups of Japanese white rabbits underwent either PBOO by mild ligation of the urethra (2- and 4 week PBOO) or no obstruction (2- and 4-week sham). Histopathological examination was performed by Elastica van Gieson staining, scanning electron microscopy, transmission electron microscopy, and ultra-high voltage electron microscopy. The number of pixels representing elastin fibers in computerized images was analyzed using Adobe Photoshop Version 2.0. RESULTS: Bladder weight significantly increased after PBOO. Increase in the thickness of the bladder wall was observed after obstruction on histopathological examination. On scanning electron microscopy, elastin was very thick and was found in large configurations. 3-D analysis using electron microscopic tomography revealed that elastic fibers in the bladder had a coil-like appearance in the muscle layer, with each fiber composed of several fibrils. Such structures may be closely related to the physiological function of the bladder. CONCLUSION: Elastin in the bladder assumes the form of a coil during micturition. We examined that the increase in elastin makes it difficult for elastin to stretch linearly resulting in reduced elasticity. This change may be one of the factors involved in the decrease in compliance mediated by PBOO. PMID- 26676287 TI - Rat Bladders Augmented with a Novel Bovine Pericardium-Derived Biomaterial Reconstruct Functional Tissue Structures. AB - OBJECTIVES: To determine if rat bladders augmented with an acellular Japanese bovine pericardium-derived biomaterial (CardioDISC [CD]) could support bladder reconstruction, and increase bladder volume and compliance. METHODS: Female Sprague-Dawley rats were randomly divided into three groups (n = 5 each). After partial cystectomy, bladders were closed without augmentation (non-augmentation) or augmented with porcine small intestinal submucosa (SIS) or CD, both of which are acellular. At 1, 2, 4 and 8 weeks after surgery, bladder volume and compliance were measured. The bladders were then analyzed by immunohistochemistry for smooth muscle actin (SMA), urothelium uroplakin III (UPIII), and nerve fiber S100. RESULTS: At 4 weeks after augmentation, the SMA-positive cells from the host bladder tissues were present near the regions augmented with CD. In addition, S100-positive cells were present within the CD-augmented tissues. At 8 weeks after surgery, the CD-augmented tissues contained layered SMA-positive cells, urothelium uroplakin III -positive urothelium, and S100 fibers, similar to normal bladder tissue. The SIS-augmented bladders showed similar results. At 8 weeks after augmentation, the bladder volume of CD-augmented bladders was larger than that at 4 weeks, while the SIS-augmented bladders were the same as those at 4 weeks. The bladder volume of the non-augmented group did not increase. The bladder compliance of the CD-augmented bladders at 8 weeks was significantly higher than at earlier times. The bladder compliance of neither the non-augmented nor the SIS-augmented groups increased during the study period. CONCLUSION: Acellular bovine pericardium-derived material could be a suitable biomaterial for bladder augmentations. PMID- 26676288 TI - Neuronal Nitric Oxide Synthase Gene Transfer into the Rat Prostate Using In Vivo Electroporation. AB - OBJECTIVES: It has been reported that nitric oxide (NO) mainly contributes to prostate or urethral smooth muscles relaxation, and that nitrergic innervation and neuronal NO synthase (nNOS) levels are decreased in benign prostatic hyperplasia. The purpose of the present study was to evaluate the feasibility to gene therapy for benign prostatic hyperplasia by transferring nNOS gene into the rat prostate with in vivo electroporation (EP) procedure. METHODS: Male Sprague Dawley rats were divided into four groups (sham, only EP, only nNOS injection, and nNOS gene injection with EP groups). Fifty micrograms of luciferase gene and nNOS expression vectors in 50 uL of K-PBS (potassium-phosphate buffered saline) were injected into the prostate. Immediately after the injection of these vectors, the vector injection points were electroporated by the two-square parallel electrodes. Two days after gene transfer, luciferase analysis and an immunohistochemical staining for nNOS were performed, and NO2 (-) /NO3 (-) (NOX ) release was measured using high-performance liquid chromatography coupled with the microdialysis procedure. RESULTS: The optimal electric pulse conditions were 50 V, 1 Hz and 10 msec. In vivo EP with these conditions showed the increase in the luciferase gene expression approximately 300-fold of the control group. In the nNOS gene injection with EP group, the marked nNOS immunoreactivity was observed, and NOX release was significantly higher, as compared to other groups. CONCLUSION: The results suggest that EP is a feasible technique for in vivo gene transfer into the rat prostate, and that the transferred nNOS gene functionally expresses and contributes to NO production. PMID- 26676289 TI - Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms. AB - OBJECTIVES: To measure urinary nerve growth factor (NGF) levels in patients with several urinary tract diseases under different conditions and compare with NGF levels in patients with overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: Urinary NGF levels were measured using enzyme-linked immunosorbent assay (ELISA) and normalized by urinary creatinine concentration. Patients with acute bacterial cystitis, urinary tract stone, urothelial cell carcinoma, and OAB patients after antimuscarinic therapy were evaluated. The urinary NGF levels of OAB, IC/PBS and controls from previous studies were used for comparison. NGF levels were compared among subgroups and between urinary tract diseases with or without associated OAB symptoms. The urinary NGF levels were also compared among natural filling, after normal saline filling and after potassium chloride test in a group of OAB and IC/PBS patients. RESULTS: Patients with acute bacterial cystitis, urinary tract stones or urothelial cell carcinoma had elevated NGF levels that were not associated with the presence of OAB symptoms. Symptomatic cystitis patients who had resolved OAB symptoms after antibiotic treatment had a significant decrease in urinary NGF levels. The urinary NGF levels decreased significantly in OAB patients with effective antimuscarinic treatment for 6 months, but remained stationary and higher than the controls for up to 12 months after treatment. CONCLUSION: Urinary NGF is not produced solely in patients with OAB or IC/PBS. Acute bacterial cystitis, urinary tract stones and urothelial cell carcinoma can have high urinary NGF production. PMID- 26676290 TI - Influence of Preoperative Detrusor Underactivity on the Continence Rate and Satisfaction after Midurethral Sling Patient with Stress Urinary Incontinence. AB - OBJECTIVES: We studied the influence of preoperative detrusor underactivity in patients with stress urinary incontinence on the postoperative continence rates and patient satisfaction. METHODS: Medical records of 41 female patients who had detrusor underactivity and had undergone a midurethral sling procedure with a follow up of at least 12 months were reviewed. The preoperative evaluation included a history taking, physical examination, voiding diary for 3 days and an urodynamic study. Detrusor underactivity was defined at pressure flow study by a maximal flow rate (Qmax ) less than 15 mL/sec and a detrusor pressure at maximal flow rate (Pdet Qmax ) less than 20 cmH2 O. The postoperative evaluation included a continence state, questionnaire regarding patient satisfaction (5: very satisfied, 1: very unsatisfied), uroflowmetry and residual urine volume. RESULTS: The mean patient age was 52.9 (range 39-68) years. Preoperatively, mean Qmax was 12.6 +/- 2.1 mL/sec, mean residual urine volume was 16.1 +/- 32.3 mL and mean Pdet Qmax was 13.1 +/- 4.7 cmH2 O. Postoperative continence rate was 88% (36/41). Five patients experienced minimal incontinence when they coughed violently. The amount of patients satisfied with postoperative status was 71%. Postoperatively, three patients needed medication with alpha blocker because of voiding difficulty. There was significant differences between preoperative and postoperative Qmax (13.1 +/- 0.9 mL/sec vs 17.1 +/- 0.9 mL/sec, P < 0.05). In addition postoperative residual urine volume (26.1 +/- 27.9 mL) was significantly increased compared to the preoperative residual urine volume (16.1 +/- 32.3 mL) (P < 0.05). CONCLUSION: Midurethral sling can be done safely for the patients with stress urinary incontinence and detrusor underactivity. However, the evaluation of preoperative detrusor function is important since the therapeutic outcome and postoperative voiding pattern may be affected by detrusor underactivity. PMID- 26676292 TI - Clinical Efficacy of alpha1-Adrenargic Receptor Antagonist Naftopidil 75 mg/day in Patients with Benign Prostatic Hyperplasia. AB - OBJECTIVES: The clinical efficacy and safety of 75 mg/day of naftopidil, an alpha1-adrenargic receptor antagonist, was assessed in patients with benign prostatic hyperplasia (BPH). METHODS: A total of 28 patients (mean age, 71.1 years; range, 46-86 years) with BPH were studied. Inclusion criteria were: (i) International Prostate Symptom Score (IPSS) >=8; and (ii) quality of life (QOL) index >=3. IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), and bladder diary (urinary frequency in daytime and nighttime, frequency of urinary incontinence and urgency) were evaluated before and 4 weeks after treatment with naftopidil at 75 mg/day. RESULTS: Total IPSS and QOL index were significantly decreased after treatment. Total OABSS tended to decrease after treatment, with significant improvements in the "urgency" parameter. From the bladder diary, urinary frequency in daytime and nighttime and frequency of urgency were significantly decreased after treatment. Total IPSS and QOL index in patients with previous treatment were significantly improved after treatment, with significant improvements in the "incomplete emptying,""poor flow" and "nocturia" parameters of IPSS. One case with a mild adverse effect of dizziness was encountered. CONCLUSION: These results suggest that administration of naftopidil at 75 mg/day was safe and effective for patients with BPH, regardless of the presence of previous treatment. This study indicates the feasibility of naftopidil at 75 mg/day as a first-line treatment for men with BPH, or a second line treatment in cases with symptoms of incomplete emptying, poor flow and nocturia. PMID- 26676291 TI - Efficacy of Clean Intermittent Catheterization for Urinary Incontinence in Children with Neurogenic Bladder Dysfunction Secondary to Myelodysplasia. AB - OBJECTIVES: To evaluate the efficacy of clean intermittent catheterization for urinary incontinence in myelodysplastic children. METHODS: The cohort comprised of 38 children (19 boys and 19 girls, aged between 10 months to 16 years) with neurogenic bladder secondary to myelodysplasia. Group A included 16 children who had dilated upper urinary tract or vesicoureteral reflux when clean intermittent catheterization was introduced. The remaining 22 children with normal upper urinary tract were enrolled to group B. In the present study, we defined socially acceptable continence as having completely dry or slight stress incontinence that patients can manage with several small pads. RESULTS: Of the 16 group A patients, 9 obtained socially acceptable continence by conservative management. Of the 22 group B patients, 11 reported socially acceptable continence by conservative management. Vesical compliance was significantly higher in cases who reported socially acceptable continence than in those with incontinence persistent regarding all participants (10 +/- 7.2 vs 6.8 +/- 6.2 mL/cmH2 O, P = 0.0347) and group A (9.1 +/- 6.7 vs 3.7 +/- 1.4 mL/cmH2 O, P = 0.0350). Leak point pressure was significantly higher in patients who obtained socially acceptable continence than in those having persistent incontinence regarding all participants (50 +/- 17.2 vs 25 +/- 6.6 mL/cmH2 O, P = 0.0003), group A (51 +/- 21.4 vs 26 +/- 7.2 mL/cmH2 O, P = 0.0348) and also, group B (49 +/- 12.8 vs 23.7 +/- 6.3 mL/cmH2 O, P = 0.0043). CONCLUSION: In our series, socially acceptable continence was obtained in only 20 patients (52%) by conservative management. The present study suggests that the limitation of conservative treatment seems to be apparent when they have urethral closure deficiency and/or intractable poor vesical compliance. PMID- 26676293 TI - Effect of the Amount of Hours Spent Studying on the Prevalence of Overactive Bladder in College Women. AB - OBJECTIVES: We conducted a questionnaire survey to access whether the amount of hours spent studying has an effect on the prevalence of OAB in college women. METHODS: A total of 126 (63%; mean: 23.2 years) of 200 women participants completed the questionnaire. They were divided into two groups: group A (weekly studying hour >40 h) consisted of medical female students and group B (weekly studying hour <25 h) consisted of French literature woman students. The factors related to OAB were analyzed by the chi-squared test. RESULTS: Of 126 respondents, the prevalence of OAB was prevalent in 38 (30.2%) women. There was significant difference in prevalence between the two groups: 7.0% for group A and 42.2% for group B. In group B, OAB prevalence was 66.7% for <=2 h, 41.2% for 2 <=4 h, 46.5% for 4-<=6 h, and >6 h was 23.5%. This survey showed that there is no relationship between the amount of hours spent studying and OAB. CONCLUSION: Although the amount of hours spent studying had no association with OAB in college women, OAB prevalence showed a decreasing pattern as the quantity of studying hour increases. Consequently, it is thought that the attitude toward study has more association with OAB than the quantity of studying hours. PMID- 26676294 TI - Effects of alpha1-Blockers for Lower Urinary Tract Symptoms and Sleep Disorders in Patients with Benign Prostatic Hyperplasia. AB - OBJECTIVES: We evaluated the association of lower urinary tract symptoms (LUTS) and sleep disorders (SD) in patients with benign prostatic hyperplasia (BPH). We also examined improvement of SD following the alpha1-blocker therapy for LUTS. METHODS: Sixty-eight male patients were enrolled in the study, consisting of 38 cases with LUTS and BPH (BPH group), and 30 men without significant LUTS or BPH (non-BPH group). The degree of LUTS and SD was evaluated by the International Prostate Symptom Score and the Pittsburg Sleep Quality Index (PSQI), respectively. The patients of BPH group then were treated with alpha1-blocker for 4 weeks, and were re-examined by all the questionnaires to evaluate the therapeutic efficacies. RESULTS: The correlation analyses showed a significant association of LUTS with SD in BPH group (r = 0.4995, P = 0.0068). Twenty cases (52.6%) in BPH group showed 5.5 or more PSQI scores. Following 4 weeks of alpha1 blocker administration, the average PSQI decreased significantly from 6.3 to 4.8 points (P < 0.001). Significant improvement was observed in domains of "sleep quality" and "sleep disturbances" among PSQI (P = 0.0215 and 0.0391, respectively). Moreover, significant association between alpha1-blocker induced improvements of nocturia and SD was identified in patients with 5.5 or more PSQI score at baseline (r = 0.445, P = 0.0334). CONCLUSION: These results suggested that SD is associated with LUTS among BPH patients and therapeutic effects of alpha1-blockers on LUTS lead to improvements of SD. PMID- 26676295 TI - Advanced endoscopic features of ulcerative colitis-associated neoplasias: Quantification of autofluorescence imaging. AB - Ulcerative colitis (UC) patients are well known to carry a higher risk of developing colorectal dysplasia/cancer. However, it is hard to detect the lesion in the early phase during colonoscopy. This pilot study was conducted to analyze the endoscopic characteristics of neoplastic lesions associated with UC using advanced imaging techniques. This is a retrospective analysis of 15 colorectal neoplastic lesion obtained from 11 UC patients during remission who underwent white-light- and advanced endoscopic imaging techniques, including chromoendoscopy, narrow-band imaging and autofluorescence imaging (AFI), and were treated with surgery. These lesions were analyzed for histology, location, size, shape, color and endoscopic features. The green/red ratio was also assessed to quantify the AFI intensity. All 11 patients had extensive colitis with the median disease duration of 14.0 years. A total of 15 lesions, consisting of 8 high-grade dysplasia and 7 cancer, was mostly located in the distal colon (86.7%, 13/15) with the mean size of 8.6 mm. The shape was protruding in 46.7% (7/15), flat elevated in 40.0% (6/15) and flat in 13.3% (2/15) and the color was red in 60.0% (9/15), same colored in 33.3% (5/15) and discolored in 6.7% (1/15). The lesion predominantly showed Kudo's neoplastic pit pattern in 86.7% (13/15; 5 type IIIL, 7 type IV and 1 type VI) on chromoendoscopy and Sano's neoplastic capillary pattern (type IIIa) in 63.6% (7/11) on narrow-band imaging, but were colored purple as neoplastic lesions in only 37.5% (3/8) on AFI. Of note, the AFI green/red ratio was significantly lower in the neoplastic lesions than UC involved areas (p=0.00014) and UC-uninvolved areas (p=0.00651) irrespective of the lesion's size and histological type. In conclusion, endoscopic analysis based on advanced imaging, in particular AFI quantitation, may be helpful to detect early stage neoplastic lesions in long standing UC. Large-scale, prospective studies are needed. PMID- 26676296 TI - Sphingomonas qilianensis sp. nov., Isolated from Surface Soil in the Permafrost Region of Qilian Mountains, China. AB - A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strain, designated X1(T), was isolated from the permafrost region of Qilian Mountains in northwest of China. Phylogenetic analyses of 16S rRNA gene sequence revealed that strain X1(T) was a member of the genus Sphingomonas and shared the highest 16S rRNA gene sequence similarity with Sphingomonas oligophenolica JCM 12082(T) (96.9%), followed by Sphingomonas glacialis CGMCC 1.8957(T) (96.7%) and Sphingomonas alpina DSM 22537(T) (96.4%). Strain X1(T) was able to grow at 15-30 degrees C, pH 6.0-10.0 and with 0-0.3% NaCl (w/v). The DNA G+C content of the isolate was 64.8 mol%. Strain X1(T)-contained Q-10 as the dominant ubiquinone and C(18:1)omega7c, C(16:1)omega7c, C(16:0) and C(14:0) 2-OH as the dominant fatty acids. The polar lipid profile of strain XI(T)-contained sphingoglycolipid, phosphatidylglycerol, phosphatidylethanolamine, one unidentified glycolipid and two unidentified phospholipid. Due to the phenotypic and genetic distinctiveness and other characteristic studied in this article, we consider X1(T) as a novel species of the genus Sphingomonas and propose to name it Sphingomonas qilianensis sp. nov. The type strain is X1(T) (=CGMCC 1.15349(T) = KCTC 42862(T)). PMID- 26676297 TI - Influence of Temperature and Copper on Oxalobacteraceae in Soil Enrichments. AB - beta-Proteobacteria is one of the most abundant phylum in soils, including autotrophic and heterotrophic ammonium-consumers with relevance in N circulation in soils. The effects of high-temperature events and phytosanitary treatments, such as copper amendments, on soil bacterial communities relevant to N-cycling remain to be studied. As an example, South Portugal soils are seasonally exposed to high-temperature periods, the temperature at the upper soil layers can reach over 40 degrees C. Here, we evaluated the dynamics of mesophilic and thermophilic bacteria from a temperate soil, in particular of heterotrophic beta Proteobacteria, regarding the ammonium equilibrium, as a function of temperature and copper treatment. Soil samples were collected from an olive orchard in southern Portugal. Selective enrichments were performed from samples under different conditions of temperature (30 and 50 degrees C) and copper supplementation (100 and 500 uM) in order to mime seasonal variations and phytosanitary treatments. Changes in the microbial communities under these conditions were examined by denaturing gradient gel electrophoresis, a molecular fingerprint technique. At moderate temperature--30 degrees C--either without or with copper addition, dominant members were identified as different strains belonging to genus Massilia, a genus of the Oxalobacteraceae (beta Proteobacteria), while at 50 degrees C, members of the Brevibacillus genus, phylum Firmicutes were also represented. Ammonium production during bacterial growth at moderate and high temperatures was not affected by copper addition. Results indicate that both copper and temperature selected specific tolerant bacterial strains with consequences for N-cycling in copper-treated orchards. PMID- 26676299 TI - Professor Sri Prakash Misra, incoming President, Indian Society of Gastroenterology 2015-2016. PMID- 26676300 TI - Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells. AB - Our previous study demonstrated that type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF) induced phosphorylation/activation of epidermal growth factor receptor (EGFR). Since human epidermal growth factor receptor 2 (HER2) has a similar molecular structure to EGFR, the present study was designed to investigate whether PKG II also inhibits HER2 activation. The human gastric cancer cell line HGC-27 was infected with an adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to increase the expression of PKG II and treated with 8-(4 chlorophenylthio)guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) to activate the kinase. Western blotting was performed to detect the tyrosine and serine/threonine phosphorylation of HER2. Co-immunoprecipitation was performed in order to determine the binding between PKG II and HER2. In addition, a QuikChange Lightning Site-Directed Mutagenesis kit was used to mutate threonine 686 of HER2 to glutamic acid or alanine. The results demonstrated that EGF treatment increased the tyrosine phosphorylation (activation) of HER2. Increasing the PKG II activity of HGC-27 cells through infection with Ad-PKG II and stimulation with 8-pCPT-cGMP inhibited the EGF-induced tyrosine phosphorylation/activation of HER2. PKG II bound directly with HER2 and caused phosphorylation of threonine 686. When threonine 686 of HER2 was mutated to alanine, which could not be phosphorylated by PKG II, the inhibitory effect of PKG II on the activation of HER2 was eradicated. When threonine 686 of HER2 was mutated to glutamic acid, which mimicked the phosphorylation of this site, treatment with EGF had no stimulating effect on tyrosine phosphorylation/activation of the mutant HER2. The results suggested that PKG II inhibits EGF-induced activation of HER2 through binding with and causing threonine 686 phosphorylation of this oncogenic protein. PMID- 26676298 TI - Ramalin-Mediated Apoptosis Is Enhanced by Autophagy Inhibition in Human Breast Cancer Cells. AB - Breast cancer, the most commonly diagnosed cancer in women worldwide, is treated in various ways. Ramalin is a chemical compound derived from the Antarctic lichen Ramalina terebrata and is known to exhibit antioxidant and antiinflammatory activities. However, its effect on breast cancer cells remains unknown. We examined the ability of ramalin to induce apoptosis and its mechanisms in MCF-7 and MDA-MB-231 human breast cancer cell lines. Ramalin inhibited cell growth and induced apoptosis in both cell lines in a concentration-dependent manner. By upregulating Bax and downregulating Bcl-2, ramalin caused cytochrome c and apoptosis-inducing factor to be released from the mitochondria into the cytosol, thus activating the mitochondrial apoptotic pathway. In addition, activated caspase-8 and caspase-9 were detected in both types of cells exposed to ramalin, whereas ramalin activated caspase-3 only in the MDA-MB-231 cells. Ramalin treatment also increased the levels of LC3-II and p62. Moreover, the inhibition of autophagy by 3-methyladenine or Atg5 siRNA significantly enhanced ramalin induced apoptosis, which was accompanied by a decrease in Bcl-2 levels and an increase in Bax levels. Therefore, autophagy appears to be activated as a protective mechanism against apoptosis in cancer cells exposed to ramalin. These findings suggest that ramalin is a potential anticancer agent for the treatment of patients with non-invasive or invasive breast cancer. PMID- 26676301 TI - Medical-ethical guidelines: Coercive measures in medicine. PMID- 26676303 TI - Pediatric Suprasellar Tumors. AB - The various childhood suprasellar tumors, while pathologically distinct, present similar clinical and surgical challenges as a result of their common anatomic location. These lesions are in close proximity to or may invade the optic nerve and chiasm, pituitary gland and infundibulum, hypothalamus, and third ventricle, leading to presenting features including visual field loss, impairment in visual acuity, endocrine dysfunction, and hydrocephalus. Though many suprasellar lesions are relatively benign in pathology, treatment may be complicated by high surgical morbidity resulting from damage to the hypothalamic-pituitary axis. Here we review the most frequent pediatric lesions occurring in the suprasellar region: craniopharyngioma, chiasmatic glioma, germ cell tumor, Rathke cleft and arachnoid cysts, pituitary adenoma, and histiocytosis. This review outlines both common presenting features and differentiating aspects of these lesions. It also includes classic radiographic presentations and treatment considerations for each lesion. PMID- 26676302 TI - Estradiol differentially induces progesterone receptor isoforms expression through alternative promoter regulation in a mouse embryonic hypothalamic cell line. AB - Progesterone receptor (PR) presents two main isoforms (PR-A and PR-B) that are regulated by two specific promoters and transcribed from alternative transcriptional start sites. The molecular regulation of PR isoforms expression in embryonic hypothalamus is poorly understood. The aim of the present study was to assess estradiol regulation of PR isoforms in a mouse embryonic hypothalamic cell line (mHypoE-N42), as well as the transcriptional status of their promoters. MHypoE-N42 cells were treated with estradiol for 6 and 12 h. Then, Western blot, real-time quantitative reverse transcription polymerase chain reaction, and chromatin and DNA immunoprecipitation experiments were performed. PR-B expression was transiently induced by estradiol after 6 h of treatment in an estrogen receptor alpha (ERalpha)-dependent manner. This induction was associated with an increase in ERalpha phosphorylation (serine 118) and its recruitment to PR-B promoter. After 12 h of estradiol exposure, a downregulation of this PR isoform was associated with a decrease of specific protein 1, histone 3 lysine 4 trimethylation, and RNA polymerase II occupancy on PR-B promoter, without changes in DNA methylation and hydroxymethylation. In contrast, there were no estradiol dependent changes in PR-A expression that could be related with the epigenetic marks or the transcription factors evaluated. We demonstrate that PR isoforms are differentially regulated by estradiol and that the induction of PR-B expression is associated to specific transcription factors interactions and epigenetic changes in its promoter in embryonic hypothalamic cells. PMID- 26676304 TI - Some options in studying side effects of drugs taken during pregnancy. PMID- 26676305 TI - Meningococcal vaccine antigen diversity in global databases. AB - The lack of an anti-capsular vaccine against serogroup B meningococcal disease has necessitated the exploration of alternative vaccine candidates, mostly proteins exhibiting varying degrees of antigenic variation. Analysis of variants of antigen-encoding genes is facilitated by publicly accessible online sequence repositories, such as the Neisseria PubMLST database and the associated Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL). We investigated six proposed meningococcal vaccine formulations by deducing the prevalence of their components in the isolates represented in these repositories. Despite high diversity, a limited number of antigenic variants of each of the vaccine antigens were prevalent, with strong associations of particular variant combinations with given serogroups and genotypes. In the MRF-MGL and globally, the highest levels of identical sequences were observed with multicomponent/multivariant vaccines. Our analyses further demonstrated that certain combinations of antigen variants were prevalent over periods of decades in widely differing locations, indicating that vaccine formulations containing a judicious choice of antigen variants have potential for long-term protection across geographic regions. The data further indicated that formulations with multiple variants would be especially relevant at times of low disease incidence, as relative diversity was higher. Continued surveillance is required to monitor the changing prevalence of these vaccine antigens. PMID- 26676306 TI - Uncommon carpal fractures. AB - Fractures of the hand are frequently encountered with injuries to the phalanges and metacarpals comprising the vast majority. Fractures of the carpal bones excluding the scaphoid, however, are fairly uncommon. Despite the rarity of fractures of the remaining seven carpal bones, they can cause a disproportionate amount of morbidity from missed diagnosis due to their subtlety as well as their frequent association with significant ligamentous disruption or even other carpal bone fractures. Delayed diagnosis can result in inadequate fracture care, which places the wrist at risk of disabling sequelae. This review focuses on the current concepts of pathophysiology, diagnosis, and treatment of carpal fractures other than the scaphoid. PMID- 26676307 TI - Monitoring cerebral tissue oxygen saturation at frontal and parietal regions during carotid artery stenting. AB - Cerebral oximetry is normally placed on the upper forehead to monitor the frontal lobe cerebral tissue oxygen saturation (SctO2). We present a case in which the SctO2 was simultaneously monitored at both frontal and parietal regions during internal carotid artery (ICA) stenting. Our case involves a 79-year-old man who presented after a sudden fall and was later diagnosed with a watershed ischemic stroke in the distal fields perfused by the left middle cerebral artery. He had diffuse atherosclerotic occlusive lesions in the carotid and cerebral arterial systems including an 85 % stenotic lesion in the left distal cervical ICA. The brain territory perfused by the left ICA was devoid of collateral flow from anterior and posterior communicating arteries due to an abnormal circle of Willis. During stenting, the SctO2 monitored at both frontal and parietal regions tracked the procedure-induced acute flow change. However, the baseline SctO2 values of frontal and parietal regions differed. The SctO2-MAP correlation was more consistent on the stroked hemisphere than the non-stroked hemisphere. This case showed that SctO2 can be reliably monitored at the parietal region, which is primarily perfused by the ICA. SctO2 of the stroked brain is more pressure dependent than the non-stroked brain. PMID- 26676308 TI - Certificate in Reverse Psychology probably not worth it. PMID- 26676310 TI - An unexpected number of bladder stones. PMID- 26676311 TI - A cross-stacked plasmonic nanowire network for high-contrast femtosecond optical switching. AB - We report an ultrafast optical switching device constructed by stacking two layers of gold nanowires into a perpendicularly crossed network, which works at a speed faster than 280 fs with an on/off modulation depth of about 22.4%. The two stacks play different roles in enhancing consistently the optical switching performance due to their different dependence on the polarization of optical electric fields. The cross-plasmon resonance based on the interaction between the perpendicularly stacked gold nanowires and its Fano-coupling with Rayleigh anomaly is the dominant mechanism for such a high-contrast optical switching device. PMID- 26676309 TI - Sublingual desmopressin is efficient and safe in the therapy of lithiasic renal colic. AB - PURPOSE: To evaluate the effects of newer sublingual desmopressin administration in lithiasic renal colic, alone or combined with a nonsteroidal anti-inflammatory drug (NSAID). METHODS: Prospective single-blind study including an initial number of 249 patients with lithiasic renal colic was randomized as follows: group NSAID (71 patients) received ketorolac tromethamine (ketorolac) 30 mg im and sublingual placebo (vitamin C), groups D1 and D2 (57 and 62 patients) received sublingual desmopressin (Minirin Melt), 60 and 120 MUg, respectively, whereas group C (59 patients) received a combination of 30 mg im ketorolac and 60 MUg sublingual desmopressin. Pain intensity was assessed using the visual analogue scale before and thirty minutes after drug administration. Patients experiencing pain aggravation were rescued and excluded from the study. RESULTS: Dropout incidence was higher in the NSAID group than in the groups treated with desmopressin in monotherapy or combined with ketorolac (p < 0.05). Pain intensity was diminished at least as potently by the monotherapy with desmopressin and ketorolac. The higher dose of desmopressin and the combination therapy decreased pain intensity with 56 and 59%, respectively, significantly more than the 47% decrease obtained with ketorolac alone (p < 0.05 and p < 0.001). Mean pain decrease was higher in the combination group (C) than in the NSAID or D1 groups (p < 0.001 and p < 0.05, respectively), suggesting drug additivity. Patients did not experience severe side effects. CONCLUSIONS: Sublingual desmopressin is at least as potent as NSAID in the treatment of lithiasic renal colic. The combination of sublingual desmopressin and NSAID has additive analgesic effects. PMID- 26676314 TI - Noncovalent functionalization of solid-state nanopores via self-assembly of amphipols. AB - In recent years there has been increasing interest in the development of new methods for conferring functional features to nanopore-based fluidic devices. In this work, we describe for the first time the noncovalent integration of amphoteric-amphipathic polymers, also known as "amphipols", into single conical nanopores in order to obtain signal-responsive chemical nanodevices. Highly tapered conical nanopores were fabricated by single-sided chemical etching of polycarbonate foils. After etching, the surface of the conical nanopores was chemically modified, by first metallizing the surface via gold sputtering and then by amphiphilic self-assembly of the amphipol. The net charge of adsorbed amphipols was regulated via pH changes under the environmental conditions. The pH dependent chemical equilibrium of the weak acidic and basic monomers facilitates the regulation of the ionic transport through the nanopore by adjusting the pH of the electrolyte solution. Our results demonstrate that functional amphipathic polymers are powerful building blocks for the surface modification of nanopores and might ultimately pave the way to a new means of integrating functional and/or responsive units within nanofluidic structures. PMID- 26676313 TI - Earlier diagnosis and strict diets improve the survival rate and clinical course of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. AB - AIM: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a severe metabolic disease that, without treatment, often leads to premature death or serious handicap. The aim of this study was to evaluate the clinical course of LCHADD with the homozygous 1528G>C (E510Q) mutation when patients underwent strict dietary treatment. METHODS: From 1997 to 2010, 16 patients with LCHADD were diagnosed in Finland. They were followed up, and data were prospectively collected as they emerged. Clinical data before diagnosis were retrospectively collected from hospital records. This cohort was compared with an earlier cohort of patients diagnosed from 1976 to 1996. RESULTS: The disease presented from birth to five months of age with failure to thrive, hypotonia, hepatomegaly, metabolic acidosis, cardiomyopathy and hypoketotic hypoglycaemia. In this cohort, the therapeutic delay was 0-30 days and the survival rate at the end of the study was 62.5% compared with 10-year survival rate of 14.3% for the earlier cohort. The survivors were in good overall condition, but some of them had developed mild retinopathy or mild neuropathy. CONCLUSION: Earlier diagnosis and stricter dietary regimes improved the survival rates and clinical course of patients with LCHADD in Finland. However, improvements in therapy are still needed to prevent the development of long-term complications, such as retinopathy and neuropathy. PMID- 26676315 TI - Antihyperlipidemic effect of Acanthopanax senticosus (Rupr. et Maxim) Harms leaves in high-fat-diet fed mice. AB - BACKGROUND: Metabolic syndrome is a major risk factor for a variety of obesity related diseases. Recently, the effects of functional foods have been investigated on lipid metabolism as a means to reduce lipid content in the blood, liver and adipose tissues associated with carnitine O-palmitoyltransferase (CPT) activity. Acanthopanax senticosus (Rupr. et Maxim) Harms (AS) is a medicinal herb possessing a wide spectra of functions including antioxidant, anti-inflammatory and anti-fatigue actions. Despite much research being focused on the cortical roots of AS, little information is available regarding its leaves, which are also expected to promote human health, for example by improving abnormal lipid metabolism. Here, we explored whether AS leaves affect lipid metabolism in mice fed a high-fat diet. RESULTS: The administration of AS to BALB/c mice fed a high fat diet significantly decreased plasma triglycerides (TG). CPT activity in the liver of these mice was significantly enhanced by AS treatment. CONCLUSION: These findings indicate that AS leaves have the potential to alleviate increase in plasma TG levels due to high-fat diet intake in mice, possibly by increasing mitochondrial fatty acid beta-oxidation, especially via CPT activation. Consequently, daily intake of AS leaves could promote beneficial health effects including the prevention of metabolic syndrome. (c) 2015 Society of Chemical Industry. PMID- 26676317 TI - Rickettsia amblyommii infecting Amblyomma sculptum in endemic spotted fever area from southeastern Brazil. AB - The Rickettsia bacteria include the aetiological agents for the human spotted fever (SF) disease. In the present study, a SF group Rickettsia amblyommii related bacterium was detected in a field collected Amblyomma sculptum (Amblyomma cajennense species complex) tick from a Brazilian SF endemic site in southeastern Brazil, in the municipality of Juiz de Fora, state of Minas Gerais. Genetic analysis based on genes ompA,ompB and htrA showed that the detected strain, named R. amblyommii str. JF, is related to the species R. amblyommii. PMID- 26676316 TI - Role of Acid Sphingomyelinase in Shifting the Balance Between Proinflammatory and Reparative Bone Marrow Cells in Diabetic Retinopathy. AB - The metabolic insults associated with diabetes lead to low-grade chronic inflammation, retinal endothelial cell damage, and inadequate vascular repair. This is partly due to the increased activation of bone marrow (BM)-derived proinflammatory monocytes infiltrating the retina, and the compromised function of BM-derived reparative circulating angiogenic cells (CACs), which home to sites of endothelial injury and foster vascular repair. We now propose that a metabolic link leading to activated monocytes and dysfunctional CACs in diabetes involves upregulation of a central enzyme of sphingolipid signaling, acid sphingomyelinase (ASM). Selective inhibition of ASM in the BM prevented diabetes-induced activation of BM-derived microglia-like cells and normalized proinflammatory cytokine levels in the retina. ASM upregulation in diabetic CACs caused accumulation of ceramide on their cell membrane, thereby reducing membrane fluidity and impairing CAC migration. Replacing sphingomyelin with ceramide in synthetic membrane vesicles caused a similar decrease in membrane fluidity. Inhibition of ASM in diabetic CACs improved membrane fluidity and homing of these cells to damaged retinal vessels. Collectively, these findings indicate that selective modulation of sphingolipid metabolism in BM-derived cell populations in diabetes normalizes the reparative/proinflammatory cell balance and can be explored as a novel therapeutic strategy for treating diabetic retinopathy. PMID- 26676318 TI - Clostridium difficile ribotypes in humans and animals in Brazil. AB - Clostridium difficile is an emerging enteropathogen responsible for pseudomembranous colitis in humans and diarrhoea in several domestic and wild animal species. Despite its known importance, there are few studies about C. difficile polymerase chain reaction (PCR) ribotypes in Brazil and the actual knowledge is restricted to studies on human isolates. The aim of the study was therefore to compare C. difficile ribotypes isolated from humans and animals in Brazil. Seventy-six C. difficile strains isolated from humans (n = 25), dogs (n = 23), piglets (n = 12), foals (n = 7), calves (n = 7), one cat, and one manned wolf were distributed into 24 different PCR ribotypes. Among toxigenic strains, PCR ribotypes 014/020 and 106 were the most common, accounting for 14 (18.4%) and eight (10.5%) samples, respectively. Fourteen different PCR ribotypes were detected among human isolates, nine of them have also been identified in at least one animal species. PCR ribotype 027 was not detected, whereas 078 were found only in foals. This data suggests a high diversity of PCR ribotypes in humans and animals in Brazil and support the discussion of C. difficile as a zoonotic pathogen. PMID- 26676320 TI - DNA prime-protein boost based vaccination with a conserved region of leptospiral immunoglobulin-like A and B proteins enhances protection against leptospirosis. AB - Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the Leptospira genus. Vaccination with bacterins has severe limitations. Here, we evaluated the N-terminal region of the leptospiral immunoglobulin-like B protein (LigBrep) as a vaccine candidate against leptospirosis using immunisation strategies based on DNA prime-protein boost, DNA vaccine, and subunit vaccine. Upon challenge with a virulent strain ofLeptospira interrogans, the prime-boost and DNA vaccine approaches induced significant protection in hamsters, as well as a specific IgG antibody response and sterilising immunity. Although vaccination with recombinant fragment of LigBrep also produced a strong antibody response, it was not immunoprotective. These results highlight the potential of LigBrep as a candidate antigen for an effective vaccine against leptospirosis and emphasise the use of the DNA prime-protein boost as an important strategy for vaccine development. PMID- 26676322 TI - Effect of myrrh and thyme on Trichinella spiralis enteral and parenteral phases with inducible nitric oxide expression in mice. AB - Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis. PMID- 26676321 TI - Polymerase chain reaction detection of Leishmania DNA in skin biopsy samples in Sri Lanka where the causative agent of cutaneous leishmaniasis is Leishmania donovani. AB - Leishmania donovani is the known causative agent of both cutaneous (CL) and visceral leishmaniasis in Sri Lanka. CL is considered to be under-reported partly due to relatively poor sensitivity and specificity of microscopic diagnosis. We compared robustness of three previously described polymerase chain reaction (PCR) based methods to detect Leishmania DNA in 38 punch biopsy samples from patients presented with suspected lesions in 2010. Both, Leishmania genus-specific JW11/JW12 KDNA and LITSR/L5.8S internal transcribed spacer (ITS)1 PCR assays detected 92% (35/38) of the samples whereas a KDNA assay specific forL. donovani (LdF/LdR) detected only 71% (27/38) of samples. All positive samples showed a L. donovani banding pattern upon HaeIII ITS1 PCR-restriction fragment length polymorphism analysis. PCR assay specificity was evaluated in samples containing Mycobacterium tuberculosis, Mycobacterium leprae, and human DNA, and there was no cross-amplification in JW11/JW12 and LITSR/L5.8S PCR assays. The LdF/LdR PCR assay did not amplify M. leprae or human DNA although 500 bp and 700 bp bands were observed in M. tuberculosis samples. In conclusion, it was successfully shown in this study that it is possible to diagnose Sri Lankan CL with high accuracy, to genus and species identification, using Leishmania DNA PCR assays. PMID- 26676319 TI - Immunoregulation in human malaria: the challenge of understanding asymptomatic infection. AB - Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomatic Plasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reduced Plasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodium infection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-beta) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection. PMID- 26676323 TI - Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease. AB - The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID- 26676324 TI - A unified Bayesian semiparametric approach to assess discrimination ability in survival analysis. AB - The discriminatory ability of a marker for censored survival data is routinely assessed by the time-dependent ROC curve and the c-index. The time-dependent ROC curve evaluates the ability of a biomarker to predict whether a patient lives past a particular time t. The c-index measures the global concordance of the marker and the survival time regardless of the time point. We propose a Bayesian semiparametric approach to estimate these two measures. The proposed estimators are based on the conditional distribution of the survival time given the biomarker and the empirical biomarker distribution. The conditional distribution is estimated by a linear-dependent Dirichlet process mixture model. The resulting ROC curve is smooth as it is estimated by a mixture of parametric functions. The proposed c-index estimator is shown to be more efficient than the commonly used Harrell's c-index since it uses all pairs of data rather than only informative pairs. The proposed estimators are evaluated through simulations and illustrated using a lung cancer dataset. PMID- 26676326 TI - Should Patients Choose Their Care? PMID- 26676325 TI - Differential lncRNA-mRNA co-expression network analysis revealing the potential regulatory roles of lncRNAs in myocardial infarction. AB - Previous studies have reported that long, non-coding RNAs (lncRNAs) are important in cardiovascular disease. However, the lncRNAs involved in myocardial infarction and their detailed mechanism have not been well characterized. In the present study, an affymetrix microarray associated with myocardial infarction was re annotated, following which a myocardial infarction-related differential lncRNA mRNA co-expression network (MILMN) was constructed. Subsequently, pathway enrichment analysis was used for all the mRNAs in the MILMN, and an lncRNA pathway network was constructed. It was found that the mRNAs were predominantly involved in certain cardiovascular disease-associated pathway, for example the dilated cardiomyopathy and mitogen-activated protein kinase signaling pathway. Finally, a total of 39 key lncRNAs were identified, which regulate crucial pathways in myocardial infarction. Through pathway analysis of these 39 key lncRNAs, the novel function of an annotated lncRNAs-H19 was predicted, which may regulate apoptosis signal-regulating kinase, which is a protein that promotes pathological cardiac remodeling following myocardial infarction. The results of the present study not only provide potential non-coding RNA biomarkers, but also provide further insights into understanding the molecular mechanism of lncRNAs. PMID- 26676327 TI - The Salmonella effector SteA binds phosphatidylinositol 4-phosphate for subcellular targeting within host cells. AB - Many bacterial pathogens use specialized secretion systems to deliver virulence effector proteins into eukaryotic host cells. The function of these effectors depends on their localization within infected cells, but the mechanisms determining subcellular targeting of each effector are mostly elusive. Here, we show that the Salmonella type III secretion effector SteA binds specifically to phosphatidylinositol 4-phosphate [PI(4)P]. Ectopically expressed SteA localized at the plasma membrane (PM) of eukaryotic cells. However, SteA was displaced from the PM of Saccharomyces cerevisiae in mutants unable to synthesize the local pool of PI(4)P and from the PM of HeLa cells after localized depletion of PI(4)P. Moreover, in infected cells, bacterially translocated or ectopically expressed SteA localized at the membrane of the Salmonella-containing vacuole (SCV) and to Salmonella-induced tubules; using the PI(4)P-binding domain of the Legionella type IV secretion effector SidC as probe, we found PI(4)P at the SCV membrane and associated tubules throughout Salmonella infection of HeLa cells. Both binding of SteA to PI(4)P and the subcellular localization of ectopically expressed or bacterially translocated SteA were dependent on a lysine residue near the N terminus of the protein. Overall, this indicates that binding of SteA to PI(4)P is necessary for its localization within host cells. PMID- 26676328 TI - Serum gamma-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption. AB - BACKGROUND: gamma-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults. METHODS: A total of 462 subjects (289 men and 173 women), who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated. RESULTS: As serum GGT levels increased from the lowest tertile (tertile 1) to the highest tertile (tertile 3), BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women), hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002). CONCLUSION: Serum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship. PMID- 26676329 TI - Effects of Short-Term Exenatide Treatment on Regional Fat Distribution, Glycated Hemoglobin Levels, and Aortic Pulse Wave Velocity of Obese Type 2 Diabetes Mellitus Patients. AB - BACKGROUND: Most type 2 diabetes mellitus patients are obese and have obesity related vascular complications. Exenatide treatment is well known for both decreasing glycated hemoglobin levels and reduction in body weight. So, this study aimed to determine the effects of exenatide on body composition, glycated hemoglobin levels, and vascular stiffness in obese type 2 diabetes mellitus patients. METHODS: For 1 month, 32 obese type 2 diabetes mellitus patients were administered 5 MUg of exenatide twice daily. The dosage was then increased to 10 MUg. Patients' height, body weight, glycated hemoglobin levels, lipid profile, pulse wave velocity (PWV), body mass index, fat mass, and muscle mass were measured by using Inbody at baseline and after 3 months of treatment. RESULTS: After 3 months of treatment, glycated hemoglobin levels decreased significantly (P=0.007). Triglyceride, total cholesterol, and low density lipoprotein levels decreased, while aspartate aminotransferase and alanine aminotransferase levels were no change. Body weight, and fat mass decreased significantly (P=0.002 and P=0.001, respectively), while interestingly, muscle mass did not decrease (P=0.289). In addition to, Waist-to-hip ratio and aortic PWV decreased significantly (P=0.006 and P=0.001, respectively). CONCLUSION: Effects of short term exenatide use in obese type 2 diabetes mellitus with cardiometabolic high risk patients not only reduced body weight without muscle mass loss, body fat mass, and glycated hemoglobin levels but also improved aortic PWV in accordance with waist to hip ratio. PMID- 26676330 TI - High Levels of Serum DPP-4 Activity Are Associated with Low Bone Mineral Density in Obese Postmenopausal Women. AB - BACKGROUND: Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women. METHODS: We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] >=25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups. RESULTS: A total of 124 postmenopausal women was enrolled, with a mean age of 59.9+/-7.1 years. The mean BMI of the study patients was 24.4+/-2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=-0.288, P=0.038) with BMD of the spine in obese postmenopausal women. CONCLUSION: This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women. PMID- 26676331 TI - Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma. AB - BACKGROUND: Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC). METHODS: Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing. RESULTS: The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence. CONCLUSION: The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort. PMID- 26676332 TI - Prolonged Tp-e Interval, Tp-e/QT Ratio and Tp-e/QTc Ratio in Patients with Type 2 Diabetes Mellitus. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased risk of malignant ventricular arrhythmias. Cardiac electrical inhomogeneity may be the leading cause of the increased arrhythmic risk in patients with T2DM. The peak and the end of the T wave (Tp-e) interval and associated Tp-e/QT ratio are promising measures of ventricular repolarization indicating transmural dispersion of repolarization. The aim of this study was to assess ventricular repolarization in patients with T2DM by using Tp-e interval, Tp-e/QT ratio and Tp-e/corrected QT interval (QTc) ratio. METHODS: Forty-three patients with T2DM and 43 healthy control subjects, matched by gender and age, were studied. All participants underwent electrocardiography (ECG) recording. PR, RR and QT intervals represents the ECG intervals. These are not abbreviations. In all literature these ECG intervals are written like in this text. Tp-e intervals were measured from 12 lead ECG. Rate QTc was calculated by using the Bazett's formula. Tp-e/QT ratio and Tp-e/QTc ratio were also calculated. RESULTS: Mean Tp-e interval was significantly prolonged in patients with T2DM compared to controls (79.4+/-10.3, 66.4+/-8.1 ms, respectively; P<0.001). We also found significantly higher values of Tp-e/QT ratio and Tp-e/QTc ratio in patients with diabetes than controls (0.21+/-0.03, 0.17+/-0.02 and 0.19+/-0.02, 0.16+/-0.02, respectively; P<0.001). There was no difference in terms of the other ECG parameters between the groups. CONCLUSION: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in patients with T2DM. We concluded that T2DM leads to augmentation of transmural dispersion of repolarization suggesting increased risk for ventricular arrhythmogenesis. PMID- 26676333 TI - Risk Factors Associated with Disease Recurrence among Patients with Low-Risk Papillary Thyroid Cancer Treated at the University of the Philippines-Philippine General Hospital. AB - BACKGROUND: The management of papillary thyroid carcinoma (PTC) in high-risk patients is well-standardized. However, this is not the case for low-risk patients. Filipinos show a high incidence of recurrence of thyroid cancer. Thus, the identification of risk factors for recurrence in this population could potentially identify individuals for whom radioactive iodine (RAI) therapy might be beneficial. METHODS: We reviewed the medical records of adult Filipinos with low-risk PTC who underwent near-total or total thyroidectomy at the University of the Philippines-Philippine General Hospital. Multivariate logistic regression analysis was used to determine risk factors for recurrence. RESULTS: Recurrence was documented in 51/145 of patients (35.17%) included in this study. Possible risk factors such as age, sex, family history, smoking history, tumor size, multifocality, prophylactic lymph node dissection, initial thyroglobulin (Tg) level, initial anti-thyroglobulin (anti-Tg) antibody concentration, suppression of thyroid stimulating hormone production, and RAI therapy were analyzed. Multivariate analysis revealed that a tumor diameter 2 to 4 cm (odds ratio [OR], 9.17; 95% confidence interval [CI], 1.62 to 51.88; P=0.012), a tumor diameter >4 cm (OR, 16.46; 95% CI, 1.14 to 237.31; P=0.04), and a family history of PTC (OR, 67.27; 95% CI, 2.03 to 2228.96; P=0.018) were significant predictors of recurrence. In addition, RAI therapy (OR, 0.026; 95% CI, 0.01 to 0.023; P<=0.005), an initial Tg level <=2 ng/mL (OR, 0.049; 95% CI, 0.01 to 0.23; P<=0.005), and an anti-Tg antibody level <=50 U/mL (OR, 0.087; 95% CI, 0.011 to 0.67; P=0.019) were significant protective factors. CONCLUSION: A tumor diameter >=2 cm and a family history of PTC are significant predictors of recurrence. RAI therapy and low initial titers of Tg and anti-Tg antibody are significant protective factors against disease recurrence among low-risk PTC patients. PMID- 26676334 TI - Glucose-Dependent Insulinotropic Peptide Level Is Associated with the Development of Type 2 Diabetes Mellitus. AB - BACKGROUND: Incretin hormone levels as a predictor of type 2 diabetes mellitus have not been fully investigated. Therefore, we measured incretin hormone levels to examine the relationship between circulating incretin hormones, diabetes, and future diabetes development in this study. METHODS: A nested case-control study was conducted in a Korean cohort. The study included the following two groups: the control group (n=149), the incident diabetes group (n=65). Fasting total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic peptide (GIP) levels were measured and compared between these groups. RESULTS: Fasting total GIP levels were higher in the incident diabetes group than in the control group (32.64+/-22.68 pmol/L vs. 25.54+/-18.37 pmol/L, P=0.034). There was no statistically significant difference in fasting total GLP-1 levels between groups (1.14+/-1.43 pmol/L vs. 1.39+/-2.13 pmol/L, P=0.199). In multivariate analysis, fasting total GIP levels were associated with an increased risk of diabetes (odds ratio, 1.005; P=0.012) independent of other risk factors. CONCLUSION: Fasting total GIP levels may be a risk factor for the development of type 2 diabetes mellitus. This association persisted even after adjusting for other metabolic parameters such as elevated fasting glucose, hemoglobin A1c, and obesity in the pre-diabetic period. PMID- 26676335 TI - Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease. AB - BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the beta2 adrenergic receptor (ADRB2), androgen receptor (AR), and gamma-aminobutyric acid receptor alpha3 subunit (GABRA3) genes. METHODS: This study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups. RESULTS: The frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (>=26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41). CONCLUSION: The polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD. PMID- 26676336 TI - Radiographic Characteristics of Adrenal Masses in Oncologic Patients. AB - BACKGROUND: We aimed to assess the usefulness of pre-contrast Hounsfield unit (HU) and mass size on computed tomography to differentiate adrenal mass found incidentally in oncologic patients. METHODS: From 2000 to 2012, 131 oncologic patients with adrenal incidentaloma were reviewed retrospectively. Receiver operating characteristic (ROC) curves were applied to determine the optimal cut off value of the mean HU and size for detecting adrenal metastasis. RESULTS: The median age was 18 years, and 80 patients were male. The initial mass size was 18 mm, and 71 (54.2%) of these were on the left side. A bilateral adrenal mass was found in 11 patients (8.4%). Biochemically functional masses were observed in 9.2% of patients. Thirty-six out of 119 patients with nonfunctional masses underwent adrenalectomy, which revealed metastasis in 13. The primary cancers were lung cancer (n=4), renal cell carcinoma (n=2), lymphoma (n=2), hepatocellular carcinoma (n=2), breast cancer (n=1), and others (n=2). The area under the curve for the size and HU for clinically suspicious metastasis were 0.839 (95% confidence interval [CI], 0.761 to 0.900; P<0.001) and 0.959 (95% CI, 0.898 to 0.988; P<0.001), respectively. The cut-off value to distinguish between metastasis and benign masses were 22 mm for size and 20 for HU. CONCLUSION: ROC curve results suggest that pre-contrast HU >20 can be used as a diagnostic reference to suggest metastasis in oncologic patients with adrenal masses. PMID- 26676337 TI - Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency. AB - BACKGROUND: The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. METHODS: This was a retrospective observational study that enrolled patients diagnosed with GC induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 MUg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels >=18 MUg/dL. RESULTS: Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). CONCLUSION: In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery. PMID- 26676338 TI - Understanding Metabolomics in Biomedical Research. AB - The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced. PMID- 26676339 TI - Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter. AB - Wild-type TP53 exons 5-8 contain CpG dinucleotides that are prone to methylation dependent mutation during carcinogenesis, but the regulatory effects of methylation affecting these CpG sites are unclear. To clarify this, we first assessed site-specific TP53 CpG methylation in normal and transformed cells. Both DNA damage and cell ageing were associated with site-specific CpG demethylation in exon 5 accompanied by induction of a truncated TP53 isoform regulated by an adjacent intronic promoter (P2). We then synthesized novel synonymous TP53 alleles with divergent CpG content but stable encodement of the wild-type polypeptide. Expression of CpG-enriched TP53 constructs selectively reduced production of the full-length transcript (P1), consistent with a causal relationship between intragenic demethylation and transcription. 450K methylation comparison of normal (TP53-wildtype) and cancerous (TP53-mutant) human cells and tissues revealed focal cancer-associated declines in CpG methylation near the P1 transcription start site, accompanied by rises near the alternate exon 5 start site. These data confirm that site-specific changes of intragenic TP53 CpG methylation are extrinsically inducible, and suggest that human cancer progression is mediated in part by dysregulation of damage-inducible intragenic CpG demethylation that alters TP53 P1/P2 isoform expression. (c) 2015 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID- 26676340 TI - Testicular lactate content is compromised in men with Klinefelter Syndrome. AB - Klinefelter syndrome (KS) is the most common genetic cause of human infertility, but the mechanism(s) responsible for its phenotype remain largely unknown. KS is associated with alterations in body composition and with a higher risk of developing metabolic diseases. We therefore hypothesized that KS men seeking fertility treatment possess an altered testicular metabolism profile that may hamper the nutritional support of spermatogenesis. Testicular biopsies from control (46, XY) (n = 6) and KS (47, XXY) (n = 6) individuals were collected and analyzed by proton high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy. The mRNA and protein expression of crucial glycolysis associated enzymes and transporters were evaluated in parallel by quantitative PCR and Western blot, respectively. Our data revealed altered regulation of glucose transporters (GLUT1 and GLUT3); phosphofructokinase 1, liver isoform (PFKL); and lactate dehydrogenase A (LDHA) expression in the testis of KS patients. Moreover, we detected a severe reduction in lactate and creatine accumulation within testicular tissue from KS men. The aberrant levels of the biomarkers detected in testicular biopsies of KS men may therefore be associated with the infertility phenotypes presented by these men. Mol. Reprod. Dev. 83: 208 216, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26676341 TI - Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells. AB - AIM: To determine the therapeutic potential of sphingosine kinase 1 (Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure (ALF). METHODS: Balb/c mice were randomly assigned to different groups, with ALF induced by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 MUg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1 (HMGB1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. RESULTS: The expression of Sphk1 in liver tissue and PBMCs was upregulated in GalN/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells, the resident macrophages of the liver. The survival rates of mice in the N,N dimethylsphingosine (DMS, a specific inhibitor of SphK1) treatment group were significantly higher than that of the control group (P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6, 12, and 24 h compared with that of the control group (P < 0.01 for all). Serum HMGB1 levels at 6, 12, and 24 h, as well as serum TNF-alpha, IL-6, and IL-1beta levels at 12 h, were significantly lower in the DMS treatment group than in the control group (P < 0.01 for all). Furthermore, hepatic inflammation, necrosis, and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group (43.72% +/- 5.51% vs 3.57% +/- 0.83%, chi(2) = 12.81, P < 0.01). CONCLUSION: Inhibition of SphK1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells, and so might be a potential therapeutic strategy for this disease. PMID- 26676343 TI - Editorial: Challenging Year. PMID- 26676344 TI - Promise of Urinary Nerve Growth Factor for Assessment of Overactive Bladder Syndrome. AB - Overactive bladder syndrome (OAB) is highly prevalent bladder disorder in men and women. About 10-15% of the population suffers from urgency frequency with or without urgency urinary incontinence. It is estimated that 50-75% of patients with OAB may have urodynamic detrusor overactivity (DO). Urodynamic study invasive and most of the OAB patients might not accept it as a routine assessment. Therefore, a more objective and non-invasive test for diagnosis and assessing DO from OAB patients is needed. Recently, urinary nerve growth factor (NGF) has gained great interest in detecting DO in patients with OAB. Urinary NGF level was found to increase in OAB and urodynamic DO. Urinary NGF levels correlated with severity of OAB symptoms. Patients with either idiopathic or neurogenic DO may have increased urinary NGF levels. Urinary NGF levels have been shown to decrease in patients with patients with OAB and DO who have been well treated with antimuscarinics or botulinum toxin injection, but not in those with persistent OAB after treatment. Not all patients with OAB can have an elevated urinary NGF level; it may also be increased in patients with interstitial cystitis/painful bladder syndrome and other lower urinary tract diseases, suggesting urinary NGF expression could be a product of bladder inflammation and a limited specificity of urinary NGF for diagnosing DO. The source of urinary NGF has not yet been fully explored yet. Nevertheless, urinary NGF level is likely to be a promising biomarker for diagnosis of DO from OAB patients, to monitor therapeutic outcome and predict disease progression. PMID- 26676345 TI - Efficacy of High-frequency Magnetic Stimulation of the Sacral Root in Patients with Urinary Incontinence Following a Radical Prostatectomy. AB - OBJECTIVES: We report on our initial data from a prospective study to determine the efficacy of high-frequency magnetic stimulation on the sacral root (MSSR) for the intractable post-radical prostatectomy, stress urinary incontinence (SUI). METHODS: A total of 14 men with persistent SUI after a radical prostatectomy underwent treatment once every 2 weeks over a 40-week period for a total of 20 sessions. The outcome was assessed by these variables at baseline, at immediately after the first session, and at immediately after the final (20(th) ) session. RESULTS: Mean leak episodes (per day) consistently decreased after the first to the final session (from 6.1 +/- 2.9 to 3.5 +/- 2.6, and to 3.0 +/- 2.3, P < 0.01), and it remained to be decreased following 2 months after the final session. The mean pad weight (per h) also decreased after the treatment (but no statistically significant change compared to the pretreatment level). The cystometric bladder capacity at the first desire to void and the capacity at the strong desire to void increased significantly following the high-frequency MSSR (first desire to void: from 146 +/- 43 to 182 +/- 52 mL; strong desire to void: from 224 +/- 69 to 258 +/- 60 mL, P < 0.01). No obvious complication was observed in any patients during or after the treatment. CONCLUSION: This study provides the preliminary evidence that high-frequency MSSR may potentially afford a useful option with minimal invasiveness for the patients with obstinate SUI after a radical prostatectomy. PMID- 26676346 TI - The Effect of Tamsulosin Treatment on Erectile Functions in Patients with Lower Urinary Tract Symptoms (LUTS) due to Benign Prostate Hyperplasia: Correlation between Improvement of LUTS and Erectile Function. AB - OBJECTIVES: To evaluate the impact of tamsulosin treatment on erectile function in patients with lower urinary tract symptoms (LUTS). METHODS: Seventy-five patients with LUTS received tamsulosin 0.2 mg once daily for 3 months. Subjective efficacy was assessed by International Prostatic Symptom Score (IPSS) for LUTS and International Index for Erectile Function 5 (IIEF5) for erectile dysfunction (ED). Objective efficacy was assessed by prostate volume and urine flow rate. All measurements were performed at baseline and month 3. On the basis of IPSS ratio (month 3/baseline), the patients were classified into good responders (<=0.75) and poor responders (>0.75). Good responders to ED were defined as the patients who improved IIEF5 score 3 or more. RESULTS: Seventy-four subjects completed the study. IPSS score showed significant improvement, but IIEF5 score showed no significant change. Forty-three patients (58%) were classified into good responders to LUTS. The baseline score of IIEF5 in the good responders was significantly higher than that in the poor responders. Negative correlation was recognized between IPSS ratio and baseline score of IIEF5. Nine patients (13%) were able to classify into good responders to ED, who had significantly smaller prostate volume and showed significantly lower IPSS ratio. CONCLUSIONS: The tamsulosin therapy for LUTS patients showed a significant improvement of LUTS, but no significant change of erectile functions. The better response to LUTS was seen in the milder ED patient. Tamsulosin therapy may be effective not only on LUTS but also on ED in the patients who have small prostate. PMID- 26676347 TI - Is Alcohol Consumption Associated with Male Urinary Incontinence? AB - OBJECTIVES: To investigate the association between alcohol consumption and urinary incontinence among Japanese men. METHODS: Seven hundred men aged 40-75 years were recruited from the community in middle and southern Japan. A validated food frequency questionnaire was administered face-to-face to obtain information on dietary intake and habitual alcohol consumption. Urinary incontinence status was ascertained using the International Consultation on Incontinence Questionnaire-Short Form. RESULTS: Among the 683 eligible male participants, 49 men (7.2%) experienced urine leakage for the past 2.6 years (standard deviation [SD] 1.9). Their prevalence of alcohol drinking (beer, sake, shochu, wine, whisky) was lower than others without the condition, even though the daily mean ethanol intakes were similar between the two groups, 31.8 g (SD 45.4) and 31.3 g (SD 41.9), respectively. Relative to non-drinkers, the adjusted odds of urinary incontinence were 0.43 (95% CI 0.19 to 0.96) for low ethanol intake, and up to 32 g per day and 0.53 (95% CI 0.22 to 1.28) for drinking, at most, one can (350 mL) of beer daily. However, higher levels of alcohol consumption had no significant benefit in reducing the incontinence risk. CONCLUSION: The findings suggested an inverse association between urinary incontinence and low alcohol consumption particularly beer in middle-aged and older Japanese men. PMID- 26676342 TI - Diffusion lung imaging with hyperpolarized gas MRI. AB - Lung imaging using conventional 1 H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2 * is about 1-2 ms). MRI with hyperpolarized gases (3 He and 129 Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T2 * relaxation (typical T2 * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath hold. In this review, we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of the results of modeling of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows the extraction of quantitative information on the lung microstructure at the alveolar level. From an MRI scan of less than 15 s, this approach, called in vivo lung morphometry, allows the provision of quantitative values and spatial distributions of the same physiological parameters as measured by means of 'standard' invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). In addition, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure: average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiment based on the in vivo lung morphometry technique combined with quantitative computed tomography measurements, as well as with gradient echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume and length of the acinar airways, and allow the evaluation of lung parenchymal and non-parenchymal tissue. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26676348 TI - Patient Reported Goal Achievement Following the Midurethral Sling Procedure for Female Stress Urinary Incontinence. AB - OBJECTIVES: Patient perspective is very important for evaluating surgical outcomes. We investigated patient reported goal achievement, overall satisfaction and objective outcome following the midurethral sling (MUS) procedure for female stress urinary incontinence (SUI). METHODS: The study prospectively enrolled 88 SUI patients who underwent the MUS procedure between August 2006 and December 2006. Patient examination included medical history, physical examination and an urodynamic study prior to surgery. Before surgery, patients were shown a list and asked to nominate one goal which they most wanted to achieve with surgery (i.e., the target goal). The goals were classified as: symptom-related, daily life related, personal relationship- and emotion-related, and others. Before and after the surgery, patients completed a Bristol Female Lower Urinary Tract Symptom Short Form questionnaire. At 1 year postoperatively, patients were assessed in terms of achievement of the target goal, overall satisfaction and cure rate. RESULTS: At the 1-year follow-up, overall target goals were achieved in 90.1% of patients, 82 (93.2%) patients were satisfied with the treatment, and 82 (93.2%) patients were cured. For most patients, the target goals were symptom-related (47 patients, 53.4%). The patients whose goal achievement was less than overall goal achievement were significantly less satisfied than those who fully achieved their goal, and goal achievement was also related to objective cure. CONCLUSION: Achievement of patient goals was high and could be a good measure of surgical success following MUS for female SUI. PMID- 26676349 TI - Randomized Controlled Trial to Treat Benign Prostatic Hyperplasia with Overactive Bladder Using an Alpha-blocker Combined with Anticholinergics. AB - OBJECTIVES: TAABO was a randomized, controlled trial to evaluate the efficacy and safety of combination therapy of tamsulosin (TAM) with propiverine (PROP) in men with both benign prostatic hyperplasia and overactive bladder. METHODS: It enrolled men 50 years or older who had an international prostate symptom score (IPSS) of 8 or higher, an urgency item score of 1 or higher, and a quality of life (QOL) score of 2 or higher. After 8 weeks of TAM 0.2 mg/day, patients who met the inclusion criteria (8 micturitions per 24 h and 1 urgency per 24 h, evaluated by bladder diary) and were eligible for 12-weeks of continued Treatment II. Five hundred and fifteen patients were enrolled. Thereafter, 214 patients were assigned randomly to receive either TAM alone (n = 67), TAM plus PROP 10 mg (n = 72), or TAM plus PROP 20 mg (n = 75) in Treatment II. The primary efficacy end point was a change in micturitions per 24 h documented in the bladder diary. The change from baseline in urgency episodes per 24 h, IPSS, IPSS/QOL subscore, urinary flow rate and postvoid residual volume were assessed as secondary efficacy measures. RESULTS: A total of 141 men (47 TAM, 49 TAM plus PROP 10 mg, and 45 TAM plus PROP 20 mg patients) were assessed by week 12. Compared with the TAM, TAM plus PROP 10 mg patients experienced significantly fewer micturitions (P = 0.0261), urgencies (P = 0.0093) per 24 h, lower IPSS storage (P = 0.0465), and IPSS urgency (P = 0.0252) subscores. CONCLUSIONS: These results suggest that combining TAM and 10 mg of PROP for 12 weeks provides added benefit for men with both benign prostatic hyperplasia and overactive bladder. PMID- 26676350 TI - Efficacy and Safety of Propiverine and Solifenacin for the Treatment of Female Patients with Overactive Bladder: A Crossover Study. AB - OBJECTIVES: To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB). METHODS: A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P-S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S-P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS). RESULTS: A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P-S and 44 in Group S-P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P-S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039). CONCLUSION: Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine. PMID- 26676351 TI - Efficacy, Safety and Tolerability of Fesoterodine in Asian Patients with Overactive Bladder. AB - OBJECTIVES: To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg once daily (QD) compared with placebo in Asian subjects with overactive bladder (OAB) after 12 weeks of treatment. METHODS: This phase II, dose-finding study consisted of a 2-week placebo run-in period followed by a 12-week, randomized, double-blind, placebo-controlled, treatment period. Eligible subjects were aged >=20 years with >=8 micturitions per 24 h and >=1 urgency urinary incontinence (UUI) episodes per 24 h reported in a 3-day diary. The subjects were randomized to receive placebo, fesoterodine 4 mg, or fesoterodine 8 mg QD for 12 weeks. RESULTS: Of 1232 subjects who entered the placebo run-in period, 951 received double-blind treatment. The mean number of UUI episodes per 24 h at baseline was 2.2 among the three treatment groups. The two fesoterodine groups showed statistically significant decreases from baseline in the mean number of UUI episodes per 24 h at week 12 (primary endpoint) compared with placebo. Most all-causality adverse events (e.g. dry mouth and constipation) were mild or moderate. The percentage of subjects with severe adverse events was low and similar among the treatment groups (placebo, 1.3%; fesoterodine 4 mg, 1.9%; fesoterodine 8 mg, 1.0%). CONCLUSION: Fesoterodine 4 and 8 mg QD were significantly better than placebo in improving OAB symptoms. Overall, the two fesoterodine dosing regimens were well tolerated. These results suggest that fesoterodine 4 and 8 mg QD are effective and well-tolerated treatments for OAB in Asian subjects. PMID- 26676352 TI - Severe Thigh Abscess Two Years after Transobturator Sling Operation. AB - OBJECTIVES: Tension-free vaginal tape has gained large popularity owing to the ease of the procedure and its effectiveness. These procedures were initially thought to rarely involve any significant morbid complications. The transobturator tape (TOT) procedure reproduces the natural suspension similar to the tension-free vaginal tape with a reduction in potential bladder, bowel, and vascular complications by the retropubic approach. However, the TOT procedure is not risk-free when improperly performed. We report a rare case of abscess formation after TOT. METHODS: A 45-year-old woman was admitted to the orthopedic department with the chief complaint of right side thigh pain and swelling. Pelvis MRI showed abscess formation and inflammatory changes extending into the soft tissues and muscles between the right gracilis and adductor femoris. During incision and open drainage, the remnant mesh could not be located. On urologic consult, the pelvic examination located the remnant mesh to the right upper vaginal wall. Our patient underwent excision of the mesh material. RESULTS: She had significant improvement of the leg pain and was discharged home in good condition on postoperative day 7. Ultimately, the treatment for this complication was the removal of the mesh. CONCLUSION: Treatment for thigh abscess after TOT was the removal of the mesh. All patients should be counseled about this potential complication. PMID- 26676353 TI - Reconstruction of Obliterated Vesicourethral Junction: Use of the Bulbar Urethra as a Continent Valve. AB - Reconstruction of the obliterated vesicourethral junction is both complex and difficult. Here, we report an innovative method using a mobilized bulbar urethra as a continent valve. Three patients with major problems at the vesicourethral junction underwent continent valve reconstruction. In cases 1 and 2, in which there were problems at the anastomosing site after radical prostatectomy, the bladder wall was closed, wedge resection of the midline pubic bone was performed, and a fully mobilized bulbar urethra was implanted submucosally into the anterior bladder wall. In case 2, augmentation cystoplasty using an ileal segment was required due to the small capacity of the bladder. In case 3, in which there was posterior urethra disruption associated with pelvic fracture, the bulbar urethra was implanted into the bladder wall in the same manner as in cases 1 and 2 without pubectomy. The postoperative follow-up periods were 48, 36, and 12 months, respectively. In all patients, urinary management was achieved by self catheterization postoperatively, and the patients were satisfied with their status. This newly devised continent valve construction using a bulbar urethra is effective for reconstruction of the obliterated vesicourethral junction, which markedly improves patients' quality of life. PMID- 26676354 TI - Repeated catastrophic valley infill following medieval earthquakes in the Nepal Himalaya. AB - Geomorphic footprints of past large Himalayan earthquakes are elusive, although they are urgently needed for gauging and predicting recovery times of seismically perturbed mountain landscapes. We present evidence of catastrophic valley infill following at least three medieval earthquakes in the Nepal Himalaya. Radiocarbon dates from peat beds, plant macrofossils, and humic silts in fine-grained tributary sediments near Pokhara, Nepal's second-largest city, match the timing of nearby M > 8 earthquakes in ~1100, 1255, and 1344 C.E. The upstream dip of tributary valley fills and x-ray fluorescence spectrometry of their provenance rule out local sources. Instead, geomorphic and sedimentary evidence is consistent with catastrophic fluvial aggradation and debris flows that had plugged several tributaries with tens of meters of calcareous sediment from a Higher Himalayan source >60 kilometers away. PMID- 26676356 TI - Optimal control for an age-structured model for the transmission of hepatitis B. AB - One of the characteristics of HBV transmission is the age structure of the host population and the vertical transmission of the disease. That is the infection is transmitted directly from infected mother to an embryo, fetus, or baby during pregnancy or childbirth (the perinatal infection). We formulated an age structured model for the transmission dynamics of HBV with differential infectivity: symptomatic and asymptomatic infections. The model without intervention strategies is completely analyzed. We compute the basic reproduction number which determines the outcome of the disease. We also compute equilibria and study their stability. The sensitivity analysis of the initial model parameters is performed (to determine the impact of control-related parameters on outbreak severity). Using optimal control theory, we determine the cost-effective balance of three interventions methods which minimizes HBV-related deaths as well as the costs associated with intervention. PMID- 26676355 TI - Geomorphic and geologic controls of geohazards induced by Nepal's 2015 Gorkha earthquake. AB - The Gorkha earthquake (magnitude 7.8) on 25 April 2015 and later aftershocks struck South Asia, killing ~9000 people and damaging a large region. Supported by a large campaign of responsive satellite data acquisitions over the earthquake disaster zone, our team undertook a satellite image survey of the earthquakes' induced geohazards in Nepal and China and an assessment of the geomorphic, tectonic, and lithologic controls on quake-induced landslides. Timely analysis and communication aided response and recovery and informed decision-makers. We mapped 4312 coseismic and postseismic landslides. We also surveyed 491 glacier lakes for earthquake damage but found only nine landslide-impacted lakes and no visible satellite evidence of outbursts. Landslide densities correlate with slope, peak ground acceleration, surface downdrop, and specific metamorphic lithologies and large plutonic intrusions. PMID- 26676357 TI - Adaptive dynamics of saturated polymorphisms. AB - We study the joint adaptive dynamics of n scalar-valued strategies in ecosystems where n is the maximum number of coexisting strategies permitted by the (generalized) competitive exclusion principle. The adaptive dynamics of such saturated systems exhibits special characteristics, which we first demonstrate in a simple example of a host-pathogen-predator model. The main part of the paper characterizes the adaptive dynamics of saturated polymorphisms in general. In order to investigate convergence stability, we give a new sufficient condition for absolute stability of an arbitrary (not necessarily saturated) polymorphic singularity and show that saturated evolutionarily stable polymorphisms satisfy it. For the case [Formula: see text], we also introduce a method to construct different pairwise invasibility plots of the monomorphic population without changing the selection gradients of the saturated dimorphism. PMID- 26676358 TI - 5th International ACC Symposium: Classification of Adrenocortical Cancers from Pathology to Integrated Genomics: Real Advances or Lost in Translation? AB - For the clinician, despite its rarity, adrenocortical cancer is a heterogeneous tumor both in term of steroid excess and tumor evolution. For patient management, it is crucial to have an accurate vision of this heterogeneity, in order to use a correct tumor classification. Pathology is the best way to classify operated adrenocortical tumors: to recognize their adrenocortical nature and to differentiate benign from malignant tumors. Among malignant tumors pathology also aims at prognosis assessment. Although progress has being made for prognosis assessment, there is still a need for improvement. Recent studies have established the value of Ki67 for adrenocortical cancer (ACC) prognostication, aiming also at standardization to reduce variability. The use of genomics to study adrenocortical tumors gives a very new insight in their pathogenesis and molecular classification. Genomics studies of ACC give now a clear description of the mRNA (transcriptome) and miRNA expression profile, as well as chromosomal and methylation alterations. Exome sequencing also established firmly the list of the main ACC driver genes. Interestingly, genomics study of ACC also revealed subtypes of malignant tumors with different pattern of molecular alterations, associated with different outcome. This leads to a new vision of adrenocortical tumors classification based on molecular analysis. Interestingly, these molecular classifications meet also the results of pathological analysis. This opens new perspectives on the development and use of various molecular tools to classify, along with pathological analysis, ACC, and guides patient management at the area of precision medicine. PMID- 26676360 TI - Superantigen influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosus patients. AB - Risk posed by microbial superantigens in triggering or exacerbating SLE in genetically predisposed individuals, thereby altering the response to its treatment strategies, has not been studied. Using streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B as prototype superantigens, we have demonstrated that they profoundly affect the magnitude of polyclonal T cell response, particularly CD4(+) T cells and expression of CD45RA and CD45RO, and cytokine secretion in vitro in SLE patient PBMCs. Also, reduced proportions of FoxP3 expressing CD4(+)CD25(+) T cells were detected in SLE as compared to healthy control PBMCs. Furthermore, polymorphism in IL-10 and TGF-beta showed significant association with SLE in our study population. These results indicate that accumulation of superantigen-reactive T cells and cytokine polymorphism may cause disease exacerbation, relapse, or therapeutic resistance in SLE patients. Attempts to contain colonizing and/or superantigen-producing microbial agents in SLE patients in addition to careful monitoring of their therapy may be worthwhile in decreasing disease severity or preventing frequent relapses. The study suggests that superantigen interference in conjunction with cytokine polymorphism may play a role in immune dysregulation, thereby contributing to autoimmunity in SLE. Therefore, changes in T cell phenotypes and cytokine secretion might be good indicators of therapeutic efficacy in these patients. PMID- 26676361 TI - Gluten ataxia is better classified as non-celiac gluten sensitivity than as celiac disease: a comparative clinical study. AB - Gluten ataxia (GA) has customarily been considered to be the main neurological manifestation of celiac disease (CD). In recent years, the condition of non celiac gluten sensitivity (NCGS) has been defined, which includes some patients who are not considered "true celiacs." We performed a comparative clinicopathological study of these three entities. We studied 31 GA, 48 CD and 37 NCGS patients, prospectively in the same center for a period of 7 years. The protocol study included two serological determinations for gluten sensitivity [anti-gliadin IgA and IgG (AGA) and anti-tissue transglutaminase IgA (TG) antibodies], HLA-DQ2 typing, and duodenal histological assessment. Demographics and investigative findings were compared. Females were 55 % in GA, 75 % in CD (p < 0.001), and 47 % in NCGS (N.S.). GA patients were older (59 +/- 14 years) than CD (43 +/- 13 years) and NCGS (41 +/- 8 years) groups (p < 0.001). AGA positivity was higher in GA (100 %) than in CD (48 %) groups (p < 0.001), but similar to NCGS patients (89 %; N.S.); TG positivity was lower in GA (3.2 %) than in CD (33.3 %; p < 0.001), but similar to NCGS (2.7 %; N.S.). DQ2 (+) was lower in GA (32.2 %) than in CD (89.6 %; p < 0.001), but similar to NCGS (29.7 %; N.S.). Lymphocytic enteritis (Marsh type 1) was lower in GA (9.6 %) than in CD (66.7 %; p < 0.001), but similar to NCGS (10.8 %; N.S.). The other gluten sensitivity related characteristics measured were different to CD patients, but very close to NCGS. We conclude that GA patients are better classified within the NCGS group, than within CD. PMID- 26676359 TI - Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome. AB - Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. PMID- 26676363 TI - Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas. AB - Epigenetic regulation plays a significant role in gliomas. However, how methylation and long non-coding RNA (lncRNA) cooperates to regulate gliomas progression is largely unknown. In this investigation we showed that the downregulation of MEG3 expression due to hypermethylation of MEG3 was observed in gliomas tissues. Treatment of glioma cells with the DNA methylation inhibitor 5 Aza-2'-deoxycytidine (5-AzadC) decreased aberrant hypermethylation of the MEG3 promoter and prevented the loss of MEG3 expression. In addition, DNMT1 was involved in MEG3 promoter methylation, and was inversely correlated with MEG3 expression in gliomas. The inhibition of DNMT1 repressed the proliferation, clone formation, and induced apoptosis in glioma cells. Importantly, the inhibition of DNMT1 contributed to the activation of p53 pathways in gliomas cells. These results suggest that DNMT1-mediated MEG3 hypermethylation caused the loss of MEG3 expression, followed by the inhibition of the p53 pathways in gliomas. PMID- 26676364 TI - Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. AB - The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat. One isolate from chicken meat belonged to the epidemic spreading sequence type ST131. In addition to IncI2, an incX4 replicon was found to be linked to mcr-1. This report follows a recent detection of mcr-1 in E. coli from animals, food and humans in China. PMID- 26676362 TI - N-Glycan-based ER Molecular Chaperone and Protein Quality Control System: The Calnexin Binding Cycle. AB - Helenius and colleagues proposed over 20-years ago a paradigm-shifting model for how chaperone binding in the endoplasmic reticulum was mediated and controlled for a new type of molecular chaperone- the carbohydrate-binding chaperones, calnexin and calreticulin. While the originally established basics for this lectin chaperone binding cycle holds true today, there has been a number of important advances that have expanded our understanding of its mechanisms of action, role in protein homeostasis, and its connection to disease states that are highlighted in this review. PMID- 26676365 TI - Effects of hydrogen sulfide on myocardial fibrosis and PI3K/AKT1-regulated autophagy in diabetic rats. AB - Myocardial fibrosis is the predominant pathological characteristic of diabetic myocardial damage. Previous studies have indicated that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, there is little research investigating the effect of H2S on myocardial fibrosis in diabetes. The present study aimed to investigate the effects of H2S on the progression of myocardial fibrosis induced by diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Sodium hydrosulfide (NaHS) was used as an exogenous donor of H2S. After 8 weeks, expression levels of cystathionine-gamma-lyase were determined by western blot analysis and morphological changes in the myocardium were assessed by hematoxylin and eosin staining and Masson staining. The hydroxyproline content and fibrosis markers were determined by a basic hydrolysis method and western blot analysis, respectively. Autophagosomes were observed under transmission electron microscopy. Expression levels of autophagy-associated proteins and their upstream signaling molecules were also evaluated by western blotting. The results of the current study indicated that diabetes induced marked myocardial fibrosis, enhanced myocardial autophagy and suppressed the phosphatidylinositol-4,5 bisphosphate 3-kinase/RAC-alpha serine/threonine-protein kinase (PI3K/AKT1) signaling pathway. By contrast, following treatment with NaHS, myocardial fibrosis was ameliorated, myocardial autophagy was decreased and the PI3K/AKT1 pathway suppression was reversed. The results of the present study demonstrated that the protective effect of H2S against diabetes-induced myocardial fibrosis may be associated with the attenuation of autophagy via the upregulation of the PI3K/AKT1 signaling pathway. PMID- 26676366 TI - Medications, "Natural" Products, and Pharmacovigilance during Breastfeeding: A Mixed-Methods Study on Women's Opinions. AB - BACKGROUND: In cases of pharmacotherapy, mothers are confronted with the dilemma of breastfeeding and giving up the medication or discontinuing breastfeeding in order to take the drug, thus avoiding any potential risk for the infants. OBJECTIVE: This study aimed to describe women's opinions on the use of medications and "natural" products during breastfeeding, pharmacovigilance and phytosurveillance, and the management of breastfeeding. METHODS: This was a mixed methods study with a sequential exploratory design. In the first qualitative phase, we conducted focus groups and in-depth interviews with 25 mothers attending community services. Coding and content analysis were carried out using NVivo9. We identified 4 main categories, and on this basis, we built a questionnaire administered to 248 pregnant women and new mothers attending 2 third-level hospitals. We conducted a descriptive and bivariate analysis (P <= .05) using Epi-Info v.7. RESULTS: Women show 3 main attitudes: (1) to discontinue breastfeeding in order to take the medication, (2) to "endure the pain," or (3) to use so-called natural products, perceived safer than drugs. Women expressing an "endure the pain" opinion and women who considered natural products to be safer than medications had a higher probability of knowing that babies should be exclusively breastfed for the first 6 months (respectively, odds ratio [OR] = 2.24; 95% confidence interval [CI], 1.26-3.97; OR = 4.77; 95% CI, 2.56-8.88). CONCLUSION: In the dilemma of the mothers needing drug treatment, health professionals play a crucial role. They should convey evidence-based information on the compatibility of drugs with breastfeeding and provide individualized treatments, tailored to the single mother-baby case. PMID- 26676367 TI - Controlling core/shell Au/FePt nanoparticle electrocatalysis via changing the core size and shell thickness. AB - Using a modified seed-mediated method, we synthesized core/shell Au/FePt nanoparticles (NPs) with Au sizes of 4, 7, and 9 nm and the FePt shell was controlled to have similar FePt compositions and 0.5, 1, and 2 nm thickness. We studied both core and shell effects on electrochemical and electrocatalytic properties of the Au/FePt NPs, and found that the Au core did change the redox chemistry of the FePt shell and promoted its electrochemical oxidation of methanol. The catalytic activity was dependent on the FePt thicknesses, but not much on the Au core sizes, and the 1 nm FePt shell was found to be the optimal thickness for catalyzing methanol oxidation in 0.1 M HClO4 + 0.1 M methanol, offering not only high activity (1.19 mA cm(-2) at 0.5 V vs. Ag/AgCl), but also enhanced stability. Our studies demonstrate a general approach to the design and tuning of shell catalysis in the core/shell structure to achieve optimal catalysis for important electrochemical reactions. PMID- 26676368 TI - Dutch healthcare professionals inadequately perceived if three- and four-year-old preschool children were overweight. AB - AIM: We studied whether healthcare professionals adequately perceived if preschool children were overweight and whether this was influenced by their own body mass index (BMI). METHODS: We sent 716 Dutch healthcare professionals questionnaires containing seven pictures and seven sketches of three- and four year-old children showing body weights from underweight to morbidly obese. The professionals rated the pictures on a five-point scale from too heavy to too light and chose the sketch that they felt best depicted the child's body shape. They also reported their own height and weight and their BMI was calculated. RESULTS: Of the 716 questionnaires, 346 (48.3%) were returned with complete information and analysed. Healthcare professionals mostly chose sketches that showed children as being lighter than they really were. Depending on their own BMI group, the overweight child was perceived as having a normal weight by 74-79% of the healthcare professionals. The obese children were rated correctly by 44 52% of the professionals, but 14-15% said their weight was normal. The morbidly obese child was adequately assessed by 93-98% of the professionals. CONCLUSION: Healthcare professionals inadequately perceived whether three- and four-year-old children were overweight and this may have hindered early interventions, leading to overweight children becoming overweight adolescents. PMID- 26676369 TI - [Vascular resection and reconstruction techniques in pancreatic surgery]. AB - BACKGROUND: Vascular resection interventions and the associated necessity of a reconstruction for maintenance particularly of hepatic and small intestinal perfusion are important aspects especially for the surgical treatment of pancreatic cancer. An R0 resection is the only curative treatment option for patients with pancreatic cancer. Venous or arterial vascular infiltration by the tumor and the associated resection and reconstruction for complete tumor removal and establishment of a sufficient perfusion of the dependent organs represents one of the greatest challenges in pancreatic surgery. In addition the oncological significance with respect to arterial vascular resections is controversial. OBJECTIVE: In this review article the indications and technical aspects of vascular resection and reconstruction in the therapy of pancreatic cancer are presented and discussed based on the current literature. MATERIAL AND METHODS: A systematic search of Medline, Embase and the Cochrane Library was carried out to identify studies reporting the results of venous or arterial vascular resection techniques, postoperative morbidity, mortality and patient survival after surgery for pancreatic cancer. Results Pancreatic cancer with vascular infiltration should not principally be seen as non-resectable but must always be checked for the possibility of a curative resection. A decisive factor is the differentiation between venous and arterial vascular involvement. Various safe technical options are available for venous vascular resection, depending on the extent of tumor infiltration. Arterial vascular resections are associated with an increased morbidity and mortality. In selected patients a complete tumor resection and prolonged survival can be achieved by arterial vascular resection. PMID- 26676370 TI - Expert's comment concerning Grand Rounds case entitled "Intraspinal canal rod migration causing late-onset paraparesis 8 years after scoliosis surgery" (I. Obeid et al. Eur Spine J; 2014, DOI 10.1007/s00586-014-3367-y). PMID- 26676371 TI - Correction: Nanoscale structure and superhydrophobicity of sp(2)-bonded boron nitride aerogels. AB - Correction for 'Nanoscale structure and superhydrophobicity of sp(2)-bonded boron nitride aerogels' by Thang Pham et al., Nanoscale, 2015, 7, 10449-10458. PMID- 26676372 TI - A novel method for monitoring troponin T fragment from rabbit skeletal muscle during aging using quartz crystal microbalance. AB - BACKGROUND: Troponin T (TnT) is degraded during aging of meat. The proteolytic fragment of TnT, especially the 30 kDa fragment, is used as one of indices for estimating aging of meat. We have tried to use quartz crystal microbalance (QCM), which is widely used to analyze interaction among macromolecules, to detect proteolytic fragments of TnT during aging of meat. RESULT: The frequency of the QCM sensor with immobilized anti-TnT antibody in high-salt solution extracts of both myofibrils and whole meat decreased with time of aging. The staining intensity of the bands, including a 30 kDa fragment bound to anti-TnT antibody, also increased with time of aging in western blotting. These results confirm that TnT is degraded during aging and released from thin filaments, and QCM analysis is sufficiently sensitive to detect the TnT fragments. CONCLUSION: The QCM analysis of muscle and myofibrillar extracts using anti-TnT antibody-immobilized sensor can be used as a convenient tool for monitoring the extent of aging of meat. (c) 2015 Society of Chemical Industry. PMID- 26676374 TI - Care of adults in the last days of life: summary of NICE guidance. PMID- 26676373 TI - SCO2 Mediates Oxidative Stress-Induced Glycolysis to Oxidative Phosphorylation Switch in Hematopoietic Stem Cells. AB - Fanconi anemia (FA) is an inherited bone marrow (BM) failure syndrome, presumably resulting from defects in hematopoietic stem cells (HSCs). Normal HSCs depend more on glycolysis than on oxidative phosphorylation (OXPHOS) for energy production. Here, we show that FA HSCs are more sensitive to the respiration inhibitor NaN3 treatment than to glycolytic inhibitor 2-deoxy-d-glucose (2-DG), indicating more dependence on OXPHOS. FA HSCs undergo glycolysis-to-OXPHOS switch in response to oxidative stress through a p53-dependent mechanism. Metabolic stresses induce upregulation of p53 metabolic targets in FA HSCs. Inactivation of p53 in FA HSCs prevents glycolysis-to-OXPHOS switch. Furthermore, p53-deficient FA HSCs are more sensitive to 2-DG-mediated metabolic stress. Finally, oxidative stress-induced glycolysis-to-OXPHOS switch is mediated by synthesis of cytochrome c oxidase 2 (SCO2). These findings demonstrate p53-mediated OXPHOS function as a compensatory alteration in FA HSCs to ensure a functional but mildly impaired energy metabolism and suggest a cautious approach to manipulating p53 signaling in FA. PMID- 26676376 TI - Erratum: Trichuris trichiura in a post-Colonial Brazilian mummy. PMID- 26676375 TI - Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil. AB - An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosa isolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding beta-lactamases, aminoglycoside modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosa isolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and beta-lactamase production were responsible for the multidrug resistance in the isolates analysed. PMID- 26676377 TI - The residual-based predictiveness curve: A visual tool to assess the performance of prediction models. AB - It is agreed among biostatisticians that prediction models for binary outcomes should satisfy two essential criteria: first, a prediction model should have a high discriminatory power, implying that it is able to clearly separate cases from controls. Second, the model should be well calibrated, meaning that the predicted risks should closely agree with the relative frequencies observed in the data. The focus of this work is on the predictiveness curve, which has been proposed by Huang et al. (Biometrics 63, 2007) as a graphical tool to assess the aforementioned criteria. By conducting a detailed analysis of its properties, we review the role of the predictiveness curve in the performance assessment of biomedical prediction models. In particular, we demonstrate that marker comparisons should not be based solely on the predictiveness curve, as it is not possible to consistently visualize the added predictive value of a new marker by comparing the predictiveness curves obtained from competing models. Based on our analysis, we propose the "residual-based predictiveness curve" (RBP curve), which addresses the aforementioned issue and which extends the original method to settings where the evaluation of a prediction model on independent test data is of particular interest. Similar to the predictiveness curve, the RBP curve reflects both the calibration and the discriminatory power of a prediction model. In addition, the curve can be conveniently used to conduct valid performance checks and marker comparisons. PMID- 26676378 TI - Midwifery Provision of Home Birth Services: American College of Nurse-Midwives. AB - The number of women in the United States choosing to give birth at home has risen substantially in the past decade, creating an increased need for understanding of the evidence regarding the provision of midwifery care to women and families considering this option. The safety of home birth has been evaluated in observational studies in several industrialized nations, including the United States. Most studies find that women who are essentially healthy at term with a singleton fetus and give birth at home have positive outcomes and a lower rate of interventions during labor. Although some studies have found increased neonatal morbidity and mortality in newborns born at home when compared to newborns born in a hospital, the absolute numbers reported in both birth sites are very low. The purpose of this clinical bulletin is to review the evidence on provision of care to women and families who plan to give birth at home, including roles and responsibilities, shared decision making, informed consent, and ongoing assessment for birth site selection. PMID- 26676379 TI - Defining the Need for Transitional Care From Pediatric to Adult Surgery for Young Adult Patients With Surgically Corrected Congenital Anomalies. PMID- 26676380 TI - RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1. AB - Osteosarcoma is the most common type of primary malignant tumor of the bone. However, mechanisms underlying osteosarcoma cell proliferation are poorly understood. The present study shows that RBEL1, a newly identified Rab-like GTPase, may be a key regulator of osteosarcoma cell proliferation. Knockdown of RBEL1 in osteosarcoma cells resulted in impaired colony formation and cell proliferation. Cell cycle analysis suggested that RBEL1 depletion induced G1-S arrest in osteosarcoma cells. Furthermore, it was demonstrated that retinoblastoma 1 (Rb) was upregulated and activated following RBEL1 knockdown. In addition, Rb inhibitory downstream targets, such as cyclin A2, cyclin D1, c-Myc and cyclin-dependent kinase 2, were downregulated. Rb knockdown reversed RBEL1 depletion-induced tumor suppressive effects. In conclusion, the present results suggest that RBEL1 modulates cell proliferation and G1-S transition by inhibiting Rb in osteosarcoma. These results suggest a potential therapeutic target in osteosarcoma. PMID- 26676382 TI - Haematological malignancy in the intensive care unit: microbiology results and mortality. AB - BACKGROUND: Mortality prediction models of patients with a haematological malignancy admitted to an intensive care unit (ICU) do not include the presence of neutropenia and microbiology results. We performed a registry-based retrospective study of haematology patients admitted to the ICU to investigate the relation between neutropenia, microbiology results and outcome of these patients. METHODS: Neutropenia and microbiology culture results within 24 h before or after ICU admission of patients with a haematological malignancy admitted between 2004 and 2010 were described and analysed for association with 28-day mortality. RESULTS: We identified 234 individual patients with a current malignant haematological condition, of which 27% were neutropenic and 21% had a positive blood culture at admission. Most prevalent from blood cultured species were Escherichia coli and coagulase-negative staphylococci. The overall 28-day mortality was 38%. In patients with a positive blood culture but no neutropenia, 28-day mortality was 28% and in patients with neutropenia but without positive blood culture, it was 36%. The 28-day mortality of patients with both neutropenia and a positive blood culture was 55% with an adjusted (for APACHE-II score) hazard ratio (HR) of 1.8 (95%CI 1.0-3.4) compared to other hematologic patients admitted to the ICU. CONCLUSION: In patients with haematological malignancy admitted to the ICU, culture results are diverse. The combination of neutropenia and positive blood culture is associated with increased 28-day mortality. We suggest this could be of additional value when assessing mortality risk in this patient group. PMID- 26676381 TI - External validation of sTWEAK as a prognostic noninvasive biomarker for head and neck squamous cell carcinoma. AB - BACKGROUND: The main purpose of this study was to validate the prognostic significance of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in head and neck squamous cell carcinoma (HNSCC) using an independent cohort. METHODS: Data were evaluated from 153 patients with HNSCC in stages III to IV, who received radiotherapy (RT) or chemoradiotherapy. We quantified soluble TWEAK (sTWEAK) in pretreatment samples using enzyme-linked immunosorbent assay. RESULTS: The classification tree revealed a cutoff value of 322 pg/mL for sTWEAK to be ideal for discriminating between patients' disease control. Kaplan-Meier curves indicate that the disease-free survival rate in patients with high sTWEAK was significantly higher than in patients with low levels (p = .006, log-rank test). An independent link was identified between low sTWEAK and poor clinical outcome in Cox regression multivariate analysis (hazard ratio = 1.866; 95% confidence interval [CI] = 1.114-3.125; p = .001). CONCLUSION: Our study highlights the significance of this noninvasive biomarker in the discrimination according to the disease control achieved by patients who received a nonsurgical organ-preservation treatment. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1358-E1363, 2016. PMID- 26676383 TI - ASGO's Fourth Biennial Meeting, November 12th to 14th, 2015. PMID- 26676384 TI - Sentinel lymph node detection in endometrial cancer: hysteroscopic peritumoral versus cervical injection. PMID- 26676385 TI - The role of human papillomavirus testing after treatment for high-grade cervical dysplasia. PMID- 26676386 TI - Whole-brain perfusion imaging with balanced steady-state free precession arterial spin labeling. AB - Recently, balanced steady-state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal-to-noise ratio (SNR). However, the main limitation of bSSFP-ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP-ASL are proposed for distortion-free, high-resolution, whole-brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo continuous ASL (pCASL) with three-dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole-brain perfusion imaging for pCASL-bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL-bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26676387 TI - Urethral Sensations are Related to the Development of Detrusor Overactivity. AB - Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. alpha1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by alpha1A adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity. PMID- 26676388 TI - Muscarinic Receptor Binding of Imidafenacin in the Human Bladder Mucosa and Detrusor and Parotid Gland. AB - OBJECTIVES: The current study aimed to characterize comparatively the binding of imidafenacin to muscarinic receptors in the human bladder mucosa and detrusor muscle and parotid gland. METHODS: The muscarinic receptor in homogenates of human tissues (bladder mucosa and detrusor muscle and parotid gland) was measured using a radioligand binding assay with [N-methyl-(3) H]scopolamine methyl chloride ([(3) H]NMS). RESULTS: Imidafenacin competed with [(3) H]NMS for binding sites in the bladder mucosa and detrusor muscle and parotid gland, and its affinity was significantly (2.6-8.7 times) higher than that of oxybutynin. Also, the affinity of imidafenacin for muscarinic receptors was approximately two-fold higher in the parotid gland than bladder tissue. The affinity of imidafenacin in the mucosa was similar to that in the detrusor muscle, suggesting that this agent exhibits therapeutic effects by blocking muscarinic receptors in the mucosa as well as detrusor muscle. Scatchard analysis revealed that imidafenacin increased significantly (approximately four-fold) Kd values for [(3) H]NMS binding in the human detrusor muscle and parotid gland, with little effect on Bmax values. This observation indicates that imidafenacin binds to the muscarinic receptors in human tissues in a competitive and reversible manner. CONCLUSION: Imidafenacin binds to muscarinic receptors in the human bladder mucosa and detrusor muscle and parotid gland with high affinity. This agent was considered to exhibit therapeutic effects on the lower urinary tract symptoms due to an overactive bladder by blocking muscarinic receptors in the urothelium as well as detrusor muscle. PMID- 26676389 TI - Pulse Diode Laser Irradiation (830 nm) of Lumbosacral Spinal Roots Diminished Hyperreflexia-Induced by Acetic Acid or Prostaglandin E2 Infusion in Rat Urinary Bladder. AB - OBJECTIVES: Low power diode Iaser (830 nm) irradiation is a useful analgesic tool in superficial pain. Pulse laser irradiation allows us to increase the laser power because the non-irradiation time reduces heating effects and/or direct tissue damage at the irradiation area. This new irradiation device using pulse laser was applied to the dorsal skin to investigate the effects on the micturition reflex in the rat by targeting underlying sacral spinal roots. METHODS: Vesical pressure measurement during the continuous infusion of the urinary bladder with saline, acetic acid (AA, 0.1%) or prostaglandin E2 (PGE2 , 10(-5) M) were performed in un-anesthetized rats. Multi-unit recording from bladder afferent nerves preformed under urethane anesthesia. Laser irradiation, either continuously at 1 W or in 10 W-pulse mode, was delivered at 830 nm from 1.5 cm above the skin at the lumbosacral joint. RESULTS: During continuous saline infusion to the urinary bladder, neither continuous (1 W) nor pulse (10 W) laser irradiation altered the intercontraction interval and nerve firing during distention of the bladder. Pulse laser, but not continuous laser irradiation, increased the intercontraction interval with AA or PGE2 infusion and diminished nerve firing during distention of the bladder with AA or PGE2 infusion. CONCLUSION: These data indicate that pulse laser could diminish inflammation related nerve firing from the bladder. Since this laser irradiation did not affect the normal bladder distention elicited nerve firing, it appears capable of reducing urgency sensation without loss of the basic micturition reflex. PMID- 26676390 TI - Real-Time Monitoring of Blood Flow and Intravesical Pressure in the Rat Bladder. AB - OBJECTIVES: Because there is little information available about blood flow in the voiding cycle of the bladder, we performed a study in which we simultaneously monitored blood flow and intravesical pressure during the micturition cycle in a rat model. METHODS: Approximately 300 g male Wistar rats were used in this study. Cystometric studies were performed according to our previous report, and simultaneously blood flow was monitored. RESULTS: Before the micturition reflex occurred, a significant increase in bladder blood flow was observed, and this increased blood flow continued during the micturition reflex. Under the maximum contraction pressure, blood flow rapidly decreased (within 10% compared to the max level). This low level of blood flow continued for more than half a minute. CONCLUSION: Our data indicated that the blood flow in the bladder was dynamically changed during voiding. This technique may represent a strong tool to investigate bladder function under drug administrations and/or pathophysiological conditions. PMID- 26676391 TI - Early Efficacy of an alpha1 Adrenoceptor Antagonist, Naftopidil, against Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia. AB - OBJECTIVES: The present study investigated the early efficacy of naftopidil against lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). METHODS: Subjects comprised patients with LUTS suggestive of BPH who were followed prospectively for 8 weeks. Inclusion criteria were: (i) international prostate symptom score (IPSS) >=8; (ii) no previous treatment for BPH; and (iii) eligibility for naftopidil monotherapy. IPSS and quality of life index were evaluated, and uroflowmetry and residual urine volume were determined optionally. In the previous study, patients who demonstrated a decrease in total American Urological Association symptom score of 25% or more from baseline were considered responders. The ratio of onset of efficacy of naftopidil was calculated by the ratio of the number of responder in each group with the starting dose. RESULTS: Naftopidil efficacy was analyzed for 243 patients. Significant improvement of IPSS was achieved within 1-3 days after medication. Starting dosage and average dosage were identified as factors associated with the period until onset of naftopidil efficacy. Onset of efficacy was significantly quicker with a starting dosage of 50 mg/day as compared with 25 mg/day (P = 0.0047). However, ratios of onset of efficacy with starting dosages of 25, 50 and 75 mg/day were 77.9, 76.7 and 85.7%, respectively, showing no significant difference between groups (P = 0.7463). Duration to onset of efficacy with naftopidil dosage >=50 mg/day was 11.2 days, significantly early compared to dosage <50 mg/day. Incidence of adverse effect was 3.8%. CONCLUSION: Naftopidil showed early effects against LUTS suggestive of BPH within a few days. PMID- 26676392 TI - Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo Controlled Pilot Study Using Tamsulosin as an Active Control. AB - OBJECTIVES: Assess the efficacy and safety of once-daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH). METHODS: Following a 4-week placebo run-in period, 151 Korean men were randomly assigned to receive once-daily tadalafil 5 mg, tamsulosin 0.2 mg, or placebo for 12 weeks. RESULTS: The International Prostate Symptom Score (IPSS) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil (-5.8) and tamsulosin (-5.4) groups compared with placebo (-4.2, P > 0.05). Decreases in IPSS obstructive and irritative subscores, IPSS Quality of Life score, and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin, though none separated significantly from placebo. Increases in maximum urinary flow rate were small and not significantly different than placebo; the increase was largest in the tadalafil group (2.5 mL/sec), followed by the placebo (2.3 mL/sec) and tamsulosin (2.1 mL/sec) groups. The percentage of subjects reporting at least one treatment-emergent adverse event was 26.5, 13.7 and 3.9% in the tamsulosin, tadalafil and placebo groups, respectively. CONCLUSIONS: In this pilot study in Korean men, those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS, which was numerically (but not statistically) significant compared with the placebo. Tadalafil was well tolerated and few subjects discontinued the study due to treatment-emergent adverse events. Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed. PMID- 26676393 TI - Relationship between Urological Disease and Inferior Vena Cava Reflux on Color Doppler Ultrasonography. AB - OBJECTIVES: The possible relationship between urological disease and inferior vena cava (IVC) reflux was examined. METHODS: Transabdominal color Doppler ultrasonography of the IVC was performed. The patient was placed supine and the convex probe was positioned in vertical to the upper abdominal wall. Then the extent of reflux in the IVC accompanying each heart beat was examined near the diaphragm. A total of 403 patients (202 males and 201 females aged 12-90 years) were studied. The relationship between the existence of IVC reflux or its severity and urological disease was examined. RESULTS: The 202 males included 104 and 98 subjects without and with IVC reflux, respectively, while the 201 females included 64 and 137 subjects without and with IVC reflux, respectively. The prevalence of IVC reflux was significantly higher in females than males. Chronic prostatitis (18/21 subjects) in males and stress incontinence (22/23 subjects) in females were significantly related to the existence of IVC reflux. Conversely, urolithiasis was related to lack of IVC reflux in females. CONCLUSIONS: IVC reflux may be positively or negatively related to the occurrence of some urological diseases. Pelvic congestion secondary to IVC reflux may be one of the factors contributing to chronic prostatitis and stress incontinence. PMID- 26676394 TI - Comparison of the Effects by Obybutynin and Tolterodine on Spina Bifida Patients: A Pilot Crossover Study. AB - OBJECTIVES: To compare the effects of obybutynin and tolterodine in neurogenic bladder patients with spina bifida in a crossover study. METHODS: Seven myelomeningocele and one spinal lipoma cases, maintained with obybutynin and clean intermittent catheterization for more than 60 months, were enrolled. Age ranged from 8 to 23 years (mean 12.0, male/ female = 2/6). After 2 weeks of washout period, obybutynin (0.3 mg/kg, maximum 12 mg) or tolterodine (0.12 mg/kg, maximum 4 mg) was administered for 4 weeks, and then switched to the other drug for 4 weeks. At the end of the three periods, the patients and/or parents documented urinary storage status and adverse effects, and urodynamic study was performed. RESULTS: In seven cases undergoing sequential urodynamic study, the baseline compliance of the patients (6.81 +/- 1.83) increased to 9.98 +/- 4.97 by obybutynin and 10.16 +/- 2.53 by tolterodine (P < 0.05 for each). Better compliance was noted in two cases with tolterodine and in two cases with obybutynin. Stronger adverse effects were reported in three out of eight patients (37.5%) by obybutynin and three out of eight patients (37.5%) by tolterodine. Although storage effect and side effects were equivalent for total patients, markedly diverse response was noted for each patient, with five choosing tolterodine and three choosing obybutynin. CONCLUSIONS: Individualized evaluation is required for optimal choice of anticholinergics. PMID- 26676395 TI - Transition in Type of Surgery for Benign Prostatic Hyperplasia: A Multi institutional Study in Japan. AB - OBJECTIVES: This study compared the numbers and types of benign prostatic hyperplasia (BPH) surgeries performed in 2008 with those performed in 2003 to investigate changes in surgical procedures in Japan with the introduction of transurethral enucleation procedures. METHODS: Forty-three hospitals in Japan participated in this study. We examined the numbers of patients undergoing BPH surgery in 2003 and 2008. Types of BPH surgery were divided into five categories: R (resection); E (enucleation); S (urethral stent); O (open surgery); and A (ablation or others). The participating hospitals were divided into two groups, those performing E surgery (E hospitals) and those which did not (Non-E hospitals). RESULTS: The total numbers of BPH surgeries performed in all hospitals were 1610 in 2003 and 1720 in 2008. Of these, 1391 (86%) in 2003 and 1129 (66%) in 2008 were R-type, and 1 (<0%) in 2003 and 428 (25%) in 2008 were E type. There were 17 E hospitals and 26 Non-E hospitals, and other characteristics of the hospitals were similar. In the E hospitals, the total number of BPH surgeries increased from 552 in 2003 to 776 in 2008. Conversely, that in Non-E hospitals decreased from 1058 in 2003 to 944 in 2008. The rate of R-type surgery was significantly lower in E hospitals than in Non-E hospitals, even in 2003 (73 vs 94%, P < 0.01). CONCLUSION: E-type surgery increased considerably in the 5 years examined, but even in E hospitals, R-type surgery remained the main type of BPH surgery performed in 2008. PMID- 26676396 TI - Analysis of the Pressure-Flow Study in Weak Detrusor Patients with Benign Prostatic Hypertrophy. AB - OBJECTIVE: Pressure-flow study is a method used to evaluate the degree of bladder outlet obstruction and the strength of detrusor contractility during voiding. However, whether or not the operation for benign prostate hyperplasia should be avoided in detrusor underactivity patients remains controversial. To address this, we performed a retrospective analysis of our pressure-flow study data for benign prostate hyperplasia patients. We especially focused on the backgrounds of patients with weak detrusor contractility. METHODS: Patients (n = 288; average age, 71.5 years) who underwent pressure-flow study to evaluate operative indications between February 2001 and April 2010 were included in this study. We analyzed the relationships between background factors and detrusor contraction strength according to Schafer's nomogram. RESULTS: Patients with weak detrusor contractility had poor flow (5.81 mL/sec) and low voided volume (141.2 mL) compared to patients with normal (8.77 mL/sec, 202.0 mL) or strong (8.97 mL/sec, 178.3 mL) detrusor contractility. Twenty-six of 74 weak detrusor patients underwent prostate operation. The operated group had high obstruction grade (3.35, P < 0.001), but a low rate of detrusor overactivity (19.2%, P < 0.05), compared to the non-operated group (2.16, 41.7%). The operated group also had high urinary retention rate (38.5%) compared to the non-operation group (18.8%). CONCLUSION: We performed prostate surgery in patients who had episodes of urinary retention, with outlet obstruction, and with no detrusor overactivity, even in those with weak detrusor contractility. The operation may not be contraindicated for these patients. Pressure-flow study is an important tool to ensure adequate informed consent. PMID- 26676397 TI - Symptoms Predictive for Efficacy of Naftopidil in Patients with Benign Prostate Hyperplasia. AB - OBJECTIVES: To evaluate the lower urinary tract symptoms predicting the efficacy of the alpha1-adrenoreceptor (AR) antagonist naftopidil in patients with benign prostate hyperplasia. METHODS: The efficacy of naftopidil was examined on the basis of changes in the international prostate symptom score (IPSS). All patients received naftopidil (50 mg/day) for 12 weeks. We defined a "responder" as a patient whose total IPSS improved by five or more points and assessed the lower urinary tract symptoms predicting the efficacy of treatment by performing multivariate and probit analyses. RESULTS: Among 132 patients whose data could be analyzed, the efficacy rate was 50.8%. All IPSS items except the urgency score were significantly higher in the responders than the non-responders before treatment, and all IPSS items were lower in the responders after treatment. In the responder group, significant improvements were observed in the total IPSS score, quality of life (QOL) index, maximum flow rate (Qmax ), residual urine volume, and all IPSS items after treatment. In contrast, in the non-responder group, no parameter except the QOL index improved significantly. The probit analysis demonstrated that the score for weak stream (>=3) or nocturia (>=4) in the IPSS were factors predicting an effective response to naftopidil treatment. CONCLUSIONS: Weak stream and/or nocturia are the key symptoms that predict the efficacy of naftopidil treatment in patients with benign prostatic hyperplasia. Those with a score of >=3 for weak stream or of >=4 for nocturia are expected to achieve a good response in the subjective symptoms with administration of naftopidil. PMID- 26676400 TI - Prematurity, Birth Weight, and Socioeconomic Status Are Linked to Atypical Diurnal Hypothalamic-Pituitary-Adrenal Axis Activity in Young Adults. AB - In a prospective, case-controlled longitudinal design, 180 preterm and fullterm infants who had been enrolled at birth participated in a comprehensive assessment battery at age 23. Of these, 149 young adults, 34 formerly full-term and 115 formerly preterm (22 healthy preterm, 48 with medical complications, 21 with neurological complications, and 24 small for gestational age) donated five saliva samples from a single day that were assayed for cortisol to assess diurnal variation of the hypothalamic-pituitary-adrenal (HPA) axis. Analyses were conducted to determine whether prematurity category, birth weight, and socioeconomic status were associated with differences in HPA axis function. Pre- and perinatal circumstances associated with prematurity influenced the activity of this environmentally sensitive physiological system. Results are consistent with the theory of Developmental Origins of Health and Disease and highlight a possible mechanism for the link between prematurity and health disparities later in life. PMID- 26676401 TI - An Improved System for the Aqueous Lipshutz-Negishi Cross-Coupling of Alkyl Halides with Aryl Electrophiles. AB - The development of a palladacyclic precatalyst supported by a new biaryl(dialkyl)phosphine ligand (VPhos) in combination with octanoic acid/sodium octanoate as a simple and effective surfactant system provided an improved catalyst system for the rapid construction of a broad spectrum of alkylated scaffolds from alkyl zinc reagents generated in situ. PMID- 26676403 TI - [Bylaws of the German Society of Pathology]. PMID- 26676402 TI - Bioactive proanthocyanidins inhibit growth and induce apoptosis in human melanoma cells by decreasing the accumulation of beta-catenin. AB - Melanoma is a highly aggressive form of skin cancer with poor survival rate. Aberrant activation of Wnt/beta-catenin has been observed in nearly one-third of human melanoma cases thereby indicating that targeting Wnt/beta-catenin signaling could be a promising strategy against melanoma development. In the present study, we determined chemotherapeutic effect of grape seed proanthocyanidins (GSPs) on the growth of melanoma cells and validated their protective effects in vivo using a xenograft mouse model, and assessed if beta-catenin is the target of GSP chemotherapeutic effect. Our in vitro data show that treatment of A375 and Hs294t human melanoma cells with GSPs inhibit the growth of melanoma cells, which was associated with the reduction in the levels of beta-catenin. Administration of dietary GSPs (0.2 and 0.5%, w/w) in supplementation with AIN76A control diet significantly inhibited the growth of melanoma tumor xenografts in nude mice. Furthermore, dietary GSPs inhibited the xenograft growth of Mel928 (beta-catenin activated), while did not inhibit the xenograft growth of Mel1011 (beta-catenin inactivated) cells. These observations were further verified by siRNA knockdown of beta-catenin and forced overexpression of beta-catenin in melanoma cells using a cell culture model. PMID- 26676404 TI - [Discovery of the relationship between monocytes and macrophages: Attributable to Professor L.D. Leder]. PMID- 26676405 TI - Voices About a Stigma: Cancer in the Opinion of Three Different Segments in Brazilian Society. AB - The viewpoints of Brazilian opinion leaders regarding cancer are not yet well defined. Examining public perceptions of three segments of society through a qualitative study may provide clues to understanding the negative view that the population still has about the disease. Journalists, scientists and teachers participated in discussions in six focus group sessions. The findings were studied using the content analysis method, showing similar elements among these professionals, regardless of area of operation. We identified a negative view that may be contributing to or mirroring the vision of society that associates the illness with death and suffering. Although these opinion leaders believe they are able to filter certain negative aspects of media dissemination about cancer, when the disease affects them personally, the feeling of despair resembles common sense. Words such as "cure" are viewed with prejudice. On the other hand, a morbid approach arouses interest on the subject. It was also noted that the disclosure of a celebrity with cancer stands out as a decoy in the consumption of news. Such distortions may support actions that enhance communication about cancer, structured on pillars such as prevention, early diagnosis and cure. PMID- 26676406 TI - Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Nigeria, 2015. AB - Evidence of current and past Middle East respiratory syndrome coronavirus (MERS CoV) infection in dromedary camels slaughtered at an abattoir in Kano, Nigeria in January 2015, was sought by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and serology. MERS-CoV RNA was detected in 14 (11%) of 132 nasal swabs and antibody in 126 (96%) of 131 serum samples. Phylogenetic analyses demonstrate that the viruses in Nigeria are genetically distinct from those reported in the Arabian peninsula. PMID- 26676407 TI - The Clinical Utility of TIMP3 Expression in ACTH-Secreting Pituitary Tumor. AB - In recent years, the tissue inhibitor of metalloproteinase-3 (TIMP3) plays a pivotal role in tumorigenesis, while the role of TIMP3 in adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas remains unclear. In this study, 86 sporadic pituitary tumor specimens, including ACTH (40), GH (18), PRL-secreting (8), and non-functioining (20) and non-tumorous pituitary samples (n = 10) were available, and then, the mRNA and protein expression of TIMP3 was quantified by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry, respectively. Our findings showed that TIMP3 expression was significantly correlated with Ki-67 expression and the invasiveness of pituitary adenomas. TIMP3 mRNA and protein expression were reduced in ACTH-secreting pituitary adenomas and the other three types of pituitary adenomas compared to adjacent non-tumorous pituitary tissues (all p < .01). On the other hand, the expression of TIMP3 was negatively correlated with tumor size and Ki-67 in ACTH-secreting pituitary adenomas. TIMP3 mRNA expression was significantly lower in invasive pituitary adenomas than that in noninvasive ones (1.92-fold, p < .05). TIMP3 protein levels were also significantly lower in the majority of invasive adenomas (1.41-fold, p < .05) Furthermore, TIMP3 mRNA and protein expression were significantly lower in pituitary giant adenomas than those in microadenomas (2.58-fold, p < .05). In conclusion, the expression of TIMP3 is low in pituitary adenomas including ACTH-secreting pituitary adenomas and negatively associated with tumor aggressiveness. TIMPs may play a potential role in the progression of ACTH-secreting pituitary adenomas and be useful as a biomarker of invasiveness. PMID- 26676408 TI - Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. AB - The present study aimed to investigate the protective role of curcumin against oxidative stress in rat hepatic stellate cells (HSCs)-T6, and to determine the possible underlying mechanisms. HSC-T6 cells were divided into three groups: Negative control group, oxidant-treated group and curcumin-treated group. Flow cytometry and spectrophotometry were used to measure the production of reactive oxygen species (ROS), and the levels of malondialdehyde (MDA) and glutathione (GSH). Immunocytochemistry and a radioimmunoassay were used to determine the expression of smooth muscle alpha-actin (alpha-SMA) and the secretion of extracellular matrix (ECM) molecules. In addition, western blotting and immunocytochemistry were used to determine the expression levels of nuclear factor-erythroid 2-related factor (Nrf2). Treatment with glucose oxidase (GO) significantly stimulated the formation of ROS and increased the production of MDA, as compared with the control cells; however, the production of GSH was only slightly increased. In addition, treatment with GO significantly promoted the expression of alpha-SMA and the secretion of ECM molecules. Conversely, treatment with curcumin significantly decreased the levels of ROS and MDA, and significantly increased the levels of GSH. Curcumin significantly inhibited the expression of alpha-SMA and decreased the secretion of ECM molecules. Furthermore, treatment with curcumin significantly increased the nuclear expression levels of Nrf2. These results indicated that curcumin may protect rat HSCs against oxidative stress and inhibit the GO-induced activation and secretion of ECM molecules in vitro. These effects were mediated by the upregulation of Nrf2 nuclear translocation. PMID- 26676409 TI - Ultrasonography and radiography findings predicted the need for surgery in patients with necrotising enterocolitis without pneumoperitoneum. AB - AIM: The timing of surgical intervention in patients with necrotising enterocolitis (NEC) without pneumoperitoneum remains unclear. This study aimed to identify the predictors associated with surgical intervention in such patients and to assess how effective imaging reports were as an aid to surgical decision making. METHODS: We collected clinical data, laboratory investigations and imaging findings on NEC patients without pneumoperitoneum. A critical imaging report was defined as persistent dilation of bowel loops and evidence of portal venous gas on radiography and thickening of the bowel wall, absent peristalsis and evidence of echogenic-free fluid on sonography. Independent predictors of surgical NEC were identified using multivariate logistic regression analysis. Sensitivity and specificity analyses were performed for the imaging findings, and receiver operator characteristic curve analysis was used to evaluate the predictive accuracy. RESULTS: Of the 238 neonates studied, 54 (22.69%) required surgical intervention. The multivariate logistic regression analysis showed that abdominal erythema, C-reactive protein levels and the critical imaging report were independent predictors of the need for surgical intervention. The critical imaging report was the most powerful predictor of surgical NEC. CONCLUSION: Both ultrasonography and radiography findings proved helpful in predicting the need for surgery in NEC without pneumoperitoneum. PMID- 26676410 TI - Sediment contaminant surveillance in Milford Haven Waterway. AB - Sediment contaminants were monitored in Milford Haven Waterway (MHW) since 1978 (hydrocarbons) and 1982 (metals), with the aim of providing surveillance of environmental quality in one of the UK's busiest oil and gas ports. This aim is particularly important during and after large-scale investment in liquefied natural gas (LNG) facilities. However, the methods inevitably have changed over the years, compounding the difficulties of coordinating sampling and analytical programmes. After a review by the MHW Environmental Surveillance Group (MHWESG), sediment hydrocarbon chemistry was investigated in detail in 2010. Natural Resources Wales (NRW) contributed their MHW data for 2007 and 2012, collected to assess the condition of the Special Area of Conservation (SAC) designated under the European Union Habitats Directive. Datasets during 2007-2012 have thus been more comparable. The results showed conclusively that a MHW-wide peak in concentrations of sediment polycyclic aromatic hydrocarbons (PAHs), metals and other contaminants occurred in late 2007. This was corroborated by independent annual monitoring at one centrally located station with peaks in early 2008 and 2011. The spatial and temporal patterns of recovery from the 2007 peak, shown by MHW-wide surveys in 2010 and 2012, indicate several probable causes of contaminant trends, as follows: atmospheric deposition, catchment runoff, sediment resuspension from dredging, and construction of two LNG terminals and a power station. Adverse biological effects predictable in 2007 using international sediment quality guidelines were independently tested by data from monitoring schemes of more than a decade duration in MHW (starfish, limpets) and in the wider SAC (grey seals). Although not proving cause and effect, many of these potential biological receptors showed a simultaneous negative response to the elevated 2007 contamination following intense dredging activity in 2006. Wetland bird counts were typically at a peak in the winter of 2005-2006 previous to peak dredging. In the following winter 2006-2007, shelduck in the Pembroke River showed their lowest winter count, and spring 2007 was the largest ever drop in numbers of shelduck broods across MHW between successive breeding seasons. Wigeon counts in the Pembroke River were low in 2006-2007 and in late 2012 after further dredging nearby. These results are strongly supported by PAH data reported previously from invertebrate bioaccumulation studies in MHW 2007-2010, themselves closely reflecting sediment trends for PAHs in the Pembroke River and Angle Bay. PMID- 26676411 TI - Criterion definition for the identification of physical-geographical boundaries of Khorezm oasis through remotely sensed data. AB - The Khorezm oasis is one of the main ancient agricultural and cultural centers of Asia. Different studies have used administrative boundaries, without regard to the ecosystem complexity. Remote sensing is a technique that provides many advantages in relation to traditional land cover monitoring approaches. The main objective of this study was to identify the physical-geographical boundaries of Khorezm oasis and analyzed area change dynamics of the oasis using remote sensing data. Landsat 4-5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images from 1998, 2010, and 2014 were used in order to identify the oasis boundaries by analyzing the normalized difference vegetation index (NDVI). The Landsat data were radiometric normalized before the NDVI estimation. Several NDVI cutoff values were tested in order to define the more adequate value to identify the oasis boundaries (NDVI >= 0.1 for 1998 and 2010 images and NDVI >= 0.2 for 2014 images). Geographical Information System (GIS) techniques were then used to calculate the oasis area (31,885.49, 30,005.58, and 28,966.08 km(2), for 1998, 2010, and 2014, respectively) and analyze the land cover changes. The oasis presents a total area loss of 2919.41 km(2) between 1998 and 2014. The mean percentage variations between 2010 and 1998 and from 2014 to 1998 were -5.9 and 9.2 %, respectively. Therefore, the Khorezm oasis lost more than 9 % of this area between 1998 and 2014. The main areas of decrease appeared in the southern parts of the Aral Sea where the last tributaries of the Amudarya River were located. This work allowed mapping the physical-geographical boundaries of Khorezm oasis and identifying its dynamics for the analyzed period. The methodology presented in this work can be applied to other oasis regions, located in different parts of the world. PMID- 26676412 TI - Using probability-based spatial estimation of the river pollution index to assess urban water recreational quality in the Tamsui River watershed. AB - The Tamsui River watershed situated in Northern Taiwan provides a variety of water recreational opportunities such as riverbank park activities, fishing, cruising, rowing, sailing, and swimming. However, river water quality strongly affects water recreational quality. Moreover, the health of recreationists who are partially or fully exposed to polluted river water may be jeopardized. A river pollution index (RPI) composed of dissolved oxygen, biochemical oxygen demand, suspended solids, and ammonia nitrogen is typically used to gauge the river water quality and regulate the water body use in Taiwan. The purpose of this study was to probabilistically determine the RPI categories in the Tamsui River watershed and to assess the urban water recreational quality on the basis of the estimated RPI categories. First, according to various RPI categories, one dimensional indicator kriging (IK) was adopted to estimate the occurrence probabilities of the RPI categories. The maximum occurrence probability among the categories was then employed to determine the most suitable RPI category. Finally, the most serious categories and seasonal variations of RPI were adopted to evaluate the quality of current water recreational opportunities in the Tamsui River watershed. The results revealed that the midstream and downstream sections of the Tamsui River and its tributaries with poor river water quality afford low water recreational quality, and water recreationists should avoid full or limited exposure to these bodies of water. However, the upstream sections of the Tamsui River watershed with high river water quality are suitable for all water recreational activities. PMID- 26676413 TI - Entomopathogenic potential of Trichoderma longibrachiatum and its comparative evaluation with malathion against the insect pest Leucinodes orbonalis. AB - The widespread use of chemical pesticides in agriculture has led to the pollution of environmental systems and has caused various health disorders in animals and humans. Biological pest control is one of the most environmentally friendly methods in modern agriscience. Such methods protect crops from pests and do not pollute the environment. A strain of Trichoderma longibrachiatum was isolated and identified from the soil environment of the North 24 Parganas District, eastern India. A spore suspension of this fungus was used to treat Leucinodes orbonalis, one of the major pests of brinjal (eggplant, Solanum melongena). In an in vitro system, fungal antagonism was determined by median lethal dose (LD50) and median lethal time (LT50) tests against insect larvae. The LD50 and LT50 of T. longibrachiatum were 2.87 * 10(7) spores ml(-1) and 11.7 days, respectively. T. longibrachiatum was formulated into a biopesticide, and its performance was evaluated in brinjal field trials in 2012 and 2013. In the field trials, brinjal treated with three spray applications of T. longibrachiatum (10(8) spores/ml) at 15-day intervals showed a 56.02 % higher crop yield than that of the control. This treatment showed similar efficacy to that of the pesticide malathion in the field trials. The results of this study indicate that this formulation may replace malathion to control the insect pest L. orbonalis in brinjal crops. This is the first report of the entomopathogenic property of T. longibrachiatum and its evaluation against an insect pest in field trials. PMID- 26676414 TI - omega-3 in meat products: benefits and effects on lipid oxidative stability. AB - Although omega-3 intake has been associated with numerous health benefits, its addition to certain food matrices, and in particular meat products, may involve various technological barriers influencing the final quality of the products. Lipid oxidation must be highlighted due to the modification of both the sensory characteristics and the shelf-life of meat products. In order to reduce the impact of chemical changes and promote oxidative stability, the use of natural antioxidants has gained ground owing to the health and safety advantages linked to its effectiveness at reducing lipid oxidation. Many natural compounds have also been successfully tested in animal feed, in order to protect the raw meat materials and reduce the risk of lipid oxidation in processed products. This review aims to address the challenges and advantages of the incorporation of omega-3 fatty acids in raw meat materials and processed meat products, and to describe the use of different compounds to enhance lipid oxidative stability. (c) 2015 Society of Chemical Industry. PMID- 26676415 TI - Modulation of the Innate Immune Response by Human Neural Precursors Prevails over Oligodendrocyte Progenitor Remyelination to Rescue a Severe Model of Pelizaeus Merzbacher Disease. AB - Pelizaeus-Merzbacher disease (PMD) results from an X-linked misexpression of proteolipid protein 1 (PLP1). This leukodystrophy causes severe hypomyelination with progressive inflammation, leading to neurological dysfunctions and shortened life expectancy. While no cure exists for PMD, experimental cell-based therapy in the dysmyelinated shiverer model suggested that human oligodendrocyte progenitor cells (hOPCs) or human neural precursor cells (hNPCs) are promising candidates to treat myelinopathies. However, the fate and restorative advantages of human NPCs/OPCs in a relevant model of PMD has not yet been addressed. Using a model of Plp1 overexpression, resulting in demyelination with progressive inflammation, we compared side-by-side the therapeutic benefits of intracerebrally grafted hNPCs and hOPCs. Our findings reveal equal integration of the donor cells within presumptive white matter tracks. While the onset of exogenous remyelination was earlier in hOPCs-grafted mice than in hNPC-grafted mice, extended lifespan occurred only in hNPCs-grafted animals. This improved survival was correlated with reduced neuroinflammation (microglial and astrocytosis loads) and microglia polarization toward M2-like phenotype followed by remyelination. Thus modulation of neuroinflammation combined with myelin restoration is crucial to prevent PMD pathology progression and ensure successful rescue of PMD mice. These findings should help to design novel therapeutic strategies combining immunomodulation and stem/progenitor cell-based therapy for disorders associating hypomyelination with inflammation as observed in PMD. PMID- 26676417 TI - [Leukonychia totalis]. AB - Our patient presented with leukonychia totalis at the age of 15 years. Other malformations such as syndromes or underlying internal diseases did not exist. The patient's family history was unremarkable. In the classification of leukonychias, the real, usually hereditary leukonychia can be distinguished from the acquired form. The white color of the nails can be isolated, depending on its present form, appear as part of a syndrome, or as a result of internal disease. An effective treatment of hereditary leukonychia is not known. PMID- 26676416 TI - Hereditary gastrointestinal cancer. AB - Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome. PMID- 26676418 TI - [Subcutaneous panniculitis-like T-cell lymphoma : Two case reports]. AB - Histopathology, immunohistochemical, and molecular genetic findings revealed the diagnosis of subcutaneous panniculitis-like T-cell-lymphoma in two patients, aged 44 and 70 years. The clinical morphology of the lymphoma manifestations showed varied significantly. One patient presented with a singular erythematous nodule in the chin region. The other patient suffered from extended plate-like resistances and atrophy of the face, upper arms and left breast. Hemophagocytic syndrome was not present in either patient. Prognosis of subcutaneous panniculitis-like T-cell lymphoma without associated hemophagocytic syndrome is reported to be favorable. Radiotherapy of the singular lesion on the chin and systemic corticosteroids of the extended plaques induced complete remission in both patients. PMID- 26676419 TI - Health technologies for spatial analysis and situational diagnosis of the territories: contributions to nursing. PMID- 26676420 TI - Sedentary lifestyle in individuals with hypertension. AB - OBJECTIVE: to identify the prevalence of nursing diagnosis Sedentary lifestyle (SL) and to analyze its association with clinical indicators (CI) and related factors (RF) in patients with hypertension. METHOD: cross-sectional study with 285 patients with hypertension at a reference center for outpatient care in Northeastern Brazil. To collect data it was used an instrument based on operational defi nitions of the CI and RF previously validated. Four nurses rated SL as present or absent. To evaluate the association between CI and RF with the presence of SL it was applied the chi-square test. The prevalence ratio and confi dence interval was calculated to verify the magnitude of the effect between RF and SL. RESULTS: SL was identifi ed in 55.8% of the sample. Five IC and six RF showed a signifi cant association with SL. CONCLUSION: the study identifi es main indicators for inference of SL as well as their possible causal factors among people with hypertension. PMID- 26676421 TI - From frustration to coping with caring for death by nurse technicians. AB - OBJECTIVE: to understand nurse technicians' experience with caring for the death of terminal patients in ICUs and to configure a theoretical model. METHOD: qualitative study with theoretical saturation when analyzing the 10th non directive interview, having as reference Grounded Theory, Symbolic Interactionism and Bioethics. RESULTS: the core category - from frustration to coping with dignified nursing care for finitude: the acceptance of death as a therapeutic and intervenient component - emerged from the comparison of the sub-processes: when the nurse does not feel prepared for caring for death, accepting death as a therapeutic phenomenon and developing coping strategies. CONCLUSION: according to Symbolic Interactionism, a novice professional's frustration in caring for an individual for death is related to his/her interaction and interpretation of the situation as he/she feels prepared only to care for individuals for life. PMID- 26676422 TI - Children and adolescents with chronic kidney disease in haemodialysis: perception of professionals. AB - OBJECTIVE: to identify aspects impacting on quality of life for children and adolescents with chronic kidney disease on hemodialysis, from the perspective of health professionals, as an essential step for the construction of a specific module of the DISABKIDS(r) instrument. METHOD: methodological study. Data was collected between May and June 2012, through personal interviews with 12 participants, in two dialysis centers. The empirical material was analyzed according to the thematic content analysis, using the program MAXQDA - Qualitative Data Analysis Software. RESULTS: we identifi ed seven themes: self care, family support, impact of diagnosis, expectation of kidney transplant, truancy, socialization and stigma, grouped into three domains. CONCLUSION: the results showed aspects that impact the quality of life of these customers and, therefore, will be considered in the development of specifi c DISABKIDS(r) module. In addition, these aspects are relevant to the preparation and planning of actions directed towards children and adolescents with chronic kidney disease. PMID- 26676423 TI - First civil service examination for nurses at the Administrative Department of Public Service. AB - OBJECTIVE: to describe the results of the first national public service examination for nurses conducted by the Administrative Department of Public Service between 1941 and 1942. METHOD: historical-documentary research with a quantitative approach. RESULTS: 155 candidates registered, aged between 21 and 35 years old, 141 (91%) of whom were female. A total of 120 candidates passed the practical exam. Of these, 116 took the written qualification exam. In the end, 107 were approved, 74 (69.1%) of whom were temporary public nurses, 59 (55.1%) Anna Nery Nursing School alumni, and 10 among the first 20 twenty became involved with the Brazilian Association of Nursing later. CONCLUSION: although the exam legitimized the meritbased culture in the staff selection in the area of Brazilian nursing, egalitarian criteria were mitigated, especially regarding the grades applied to different kinds of exams. This resulted in a significant number of temporary nurses approved. PMID- 26676424 TI - Physical and psychological violence against the elderly: prevalence and associated factors. AB - OBJECTIVE: to verify the prevalence and associated factors to physical and psychological violence against elderlies and trace the sociodemographic and clinical indicators of this population. METHOD: household survey conducted in 729 elderlies Uberaba - MG. Data were analyzed by Chi-square test and logistic regression (p < 0,05). RESULTS: the prevalence of elderly on violence was 20.9%, and 5.9% to 20.9% for physical and psychological. Among them prevailed women; with 60?80 years; no education; with income, with their partner as the primary aggressor; negative self-perception of health, hospitalization in the last year and presence of multimorbidities. The violence has been associated with have 60?80 years, living with your partner and dependence for instrumental activities of daily living. CONCLUSION: reinforces the need for early identification of domestic violence and invest in both the old protective actions and in maintaining functional capacity and social inclusion. PMID- 26676425 TI - Replication of the training program in nonverbal communication in gerontology. AB - OBJECTIVE: to measure the rate of assimilation of applied content at immediate and subsequent moments after a nonverbal communication in gerontology training program. METHOD: descriptive and exploratory fi eld study developed in three state administered hospitals, which attend Brazilian National Health Service (SUS) clients. The duration of the training was twelve hours, applied with 102 healthcare professionals. RESULTS: the results revealed that the rate of assimilation of the content immediately after the program was satisfactory, as well as being satisfactory in the aspects concept of aging; strategies to foster the independence and autonomy of the elderly person; communication interferences linked to the elderly and the professional; recognition of non-verbal functions and dimensions. The exception was the professional perception faced with aspects that influence the success of communication. CONCLUSION: it was concluded that the replication of this program was relevant and current for the hospital context, remaining effi cient for healthcare professionals. PMID- 26676426 TI - Compliance of hand hygiene in maintaining the catheter for hemodialysis. AB - OBJECTIVE: to assess the compliance of the practice of hand hygiene in maintaining the temporary double-lumen catheter for hemodialysis, through the use of process indicator at the University Hospital of the University of Sao Paulo. METHOD: a quantitative, exploratory, descriptive, observational study. Sample consists of 155 observations of patients with catheter from March to November 2011, using the Maintenance Indicator Temporary Dual Lumen Catheter for Hemodialysis. RESULTS: the overall compliance rate was 65.8%. Of the 13 specific components evaluated, 9 (69.2%) had 100% compliance. Hand hygiene by health professionals presented one of the worst rates (83.9%). CONCLUSION: it is necessary to implement strategies to reduce the rates of non-compliance, improve quality of care and safety of patients with catheter, and explore factors that affect the process, such as structural issues, and behavioral materials. PMID- 26676427 TI - Women's temporality after cardiac surgery: contributions to nursing care. AB - OBJECTIVE: to unveil women's existential movement after cardiac surgery. METHOD: qualitative phenomenological study. The research setting was a hospital in Minas Gerais, in which ten women were interviewed between December 2011 and January 2012. RESULTS: after hospital discharge, the women experienced physical, social and emotional impairments, and expressed the desire to go back to the time before their diagnosis, because they felt as though they still had heart disease. This vague and average understanding led to three units of meaning that, from a Heideggerian hermeneutic point of view, revealed the phenomenon of cardiac surgery as a present circumstance that limited the participants' daily lives. CONCLUSION: nurses supporting women patients after cardiac surgery should promote health considering existential facets that are expressed during care. The bases for comprehensive care are revealed in singular and whole meetings of subjectivity. PMID- 26676428 TI - Conceptions of mid-level nursing professionals facing those with a chemical dependency. AB - OBJECTIVE: to describe and understand the conceptions of nursing assistants working in Psychosocial Care Centers for alcohol and drugs (CAPS ad), about the patient with addictions. METHOD: sixteen nursing assistants and technicians from nine of the CAPS ad in Sao Paulo were interviewed, and data were analyzed using the constant comparative method. RESULTS: performing the functions in the CAPS ad enabled the change in staff's conception from a stigmatizing and prejudiced view, to the concept of chemical dependence as a disease and those who are chemically dependent as patients with comorbidities and family problems, in need of help and treatment. CONCLUSION: professional practice in specialized services for alcohol and other drugs enables changes in the staff's conceptions about chemically dependent individuals, highlighting the need to include the subject of alcohol and drugs in the school curriculum. PMID- 26676429 TI - Speeches of managers about the policy of the directly observed treatment for tuberculosis. AB - OBJECTIVE: to analyze the managers' speeches about the policy transfer of the directly observed treatment (DOT) for tuberculosis control in the city of Joao Pessoa, Paraiba, Brazil. METHOD: this is a qualitative study developed in May and June, 2013 through semi-directed interviews with twenty health professionals in five health districts in Joao Pessoa/PB. The empirical material produced was analyzed according to the theoretical-analytical basis of the French Discourse Analysis by Pecheux. RESULTS: the study demonstrated weaknesses in the conduction and organization of actions in relation to the DOT. It revealed that the lack of knowledge of the managers about this policy has direct implications to the care of tuberculosis patients. CONCLUSION: the management should trace strategic plans to rethink the care practices and thus, reorganize the entire care network to users in order to effectively contribute to user adherence in the fight against tuberculosis. PMID- 26676430 TI - Family caregivers articulating the social network of a child with special health care needs. AB - In Brazil, studies rarely address the social network of a child with special health care needs (CSHCN). OBJECTIVE: the study sought to characterize the social network of the child and analyze the role of the family in its creation. METHOD: a qualitative approach was developed through five dynamics (Speaking Map) based on the creative sensitive method, with five groups of families (12 participants) in their homes. RESULTS: the critical discourse analysis of the caregivers (grandparents, siblings and neighbors) showed that the mother plays the main role in articulating the social network, with its points being linked by the hospital, primary and rehabilitation care, household, school, etc. Familial care becomes more visible at home and within the community. CONCLUSION: with the insufficient public policy that articulating healthcare facilities for CSHCN in the community, family members shape a social network characterized by a dense and fluid mesh. PMID- 26676431 TI - Convergence, divergence and diagnostic accuracy in the light of two nursing terminologies. AB - OBJECTIVE: compare divergences and convergences between the nursing diagnoses established for a case study, in the light of two nursing terminologies. METHOD: a descriptive research was undertaken. The participants were 24 nurses from public teaching hospitals (N=12) and hospital care institutions (N=12) in the Northeast of Brazil. RESULTS: in group A (6 faculty members and 6 clinical professionals), 51 diagnoses were established according to NANDA-I: 54.9% of high accuracy, 23.5% zero, 15.7% low and 5.9% moderate accuracy. In group B (6 faculty members and 6 clinical professionals), 43 declarations were established using the ICNP(r): 44.2% of zero accuracy, 39.5% high, 16.3% low. Four out of fi ve diagnostic titles of high accuracy in group A and the seven titles in group B converged; divergences were attributed to the number of combinations among the focus, judgment and location axes of the ICNP(r). CONCLUSION: a range of titles was observed with different diagnostic inferences and low diagnostic accuracy in both groups. PMID- 26676432 TI - Non-pharmacological strategies to decrease anxiety in cardiac catheterization: integrative review. AB - OBJECTIVE: to identify and review the literature on non-pharmacological strategies used for reducing anxiety in patients receiving cardiac catheterization. METHOD: this study was an integrative literature review. The research was conducted using the databases LILACS, SciELO, Medline (through BVS and PubMed) and Scopus. Studies were analyzed according to their objective, method, instruments used for evaluating patients' anxiety, and the results obtained. RESULTS: the most used strategy for reducing anxiety in patients receiving cardiac catheterization was music therapy. However, no study identifying the most appropriate time for this intervention (before, during and/or after the procedure) was found. Other strategies identified in this review were educational videos, massage, and palm therapy. CONCLUSION: the results found suggest that anxiety can be reduced using non-pharmacological strategies. PMID- 26676433 TI - Learning Incubator: an instrument to foster entrepreneurship in Nursing. AB - OBJECTIVE: this study aimed to know the contributions of the Learning Incubator to the process of lifelong education in health. METHOD: this is a qualitative field research whose data was collected from August to December 2014 by the focus group technique. The research had 34 employees of a Teaching Hospital in the central region of the state of Rio Grande do Sul that participated previously in the incubation process. RESULTS: from the data encoded by content analysis, three themes were selected: Learning Incubator - welcoming and integrating space; An instigating instrument that enhances possibilities; Continuous and lifelong education strategy. CONCLUSION: the Learning Incubator is an important instrument to foster entrepreneurship in nursing and other health areas due to its capacity of rethinking mechanized practices, to the possibility of instigating new ways of being and acting, and to the ability of creating and developing new ideas based on individual and institutional needs. PMID- 26676434 TI - Polysomnography assessment of sleep and wakefulness in premature newborns. AB - OBJECTIVE: to describe the total sleep time and its stages, total wake time, heart rate values and oxygen saturation shown by premature infants, and the influence of the periods of the day on sleep and physiological parameters. METHOD: a descriptive study was conducted of 13 hospitalized premature infants. Data collection was performed using polysomnography and unstructured observation for 24 uninterrupted hours. RESULTS: the newborns remained asleep for 59.6% of the day, predominantly in quiet sleep, with a higher mean heart rate during wakefulness (p<0.001). No difference was found between the variables related to sleep, physiological parameters and periods of the day, but in the morning a predominance of quiet sleep was observed (p=0.002). CONCLUSION: the preterm newborn presented more total sleep time than wakefulness; quiet sleep was the predominant stage, and heart rate was higher during wakefulness. PMID- 26676435 TI - Severe lactational mastitis: particularities from admission. AB - OBJECTIVE: to identify characteristics of women who have suffered severe lactational mastitis. METHOD: a descriptive, retrospective, documentary, quantitative study was performed. Data were collected from patient records of 114 hospitalized women from January of 2009 to December of 2013. Data were analyzed by using descriptive statistics. RESULTS: a higher percentage of severe lactational mastitis was found in young, primiparous women who had completed high school, who had no partner, and did not have a job; 96.5% of women had breast complications before admission and remained hospitalized an average of 4.4 days; at discharge, 23.7% of women had weaned their infants. CONCLUSION: this study showed that severe lactational mastitis can cause great harm to the woman and the baby. PMID- 26676436 TI - Medical waste in mobile prehospital care. AB - OBJECTIVE: the objective of this study is to identify how Medical Waste (MW) is managed in Mobile Prehospital Care (MPC) services in the state of Sao Paulo as well as characterize and quantify this waste. METHOD: exploratory and descriptive field study with data collection based on the methodology proposed by the Pan American Health Organization (PAHO), which was conducted over eight consecutive days to identify the production and characteristics of generated waste. RESULTS: it was found that the MW management of the MPC is not yet in line with the requirements of RDC 306/04, which could affect the occupational safety of workers, patients, the community, and the environment. CONCLUSION: it is recommended for the health managers to focus on this issue. The lack of studies with regard to MPC also indicates the need for further studies on the waste management. PMID- 26676437 TI - Job satisfaction of nursing staff in a university hospital. AB - OBJECTIVE: identify the determinants of job satisfaction of the nursing staff of a public university hospital. METHOD: secondary study with mixed data approach and simple and multiple linear regression. A total of 115 subjects participated in the study, 41 nurses and 74 nursing assistants and technicians. The data collection occurred in 2013 using the QST-Caism questionnaire. RESULTS: education, hierarchical level and workplace constitute job satisfaction determinants. However, age, gender, job and work period did not show this relationship. More educated workers held low job satisfaction if exercised not graduated nursing functions. CONCLUSION: graduated workers who perform high school functions are more unsatisfied than those who have high school function and qualification. PMID- 26676438 TI - Patient safety culture in a bone marrow transplantation unit. AB - OBJECTIVE: evaluate the patient safety culture in the perspective of health professionals from a bone marrow transplantation unit of an oncology research center, at a reference hospital for cancer treatment in Santa Catarina, Brazil. METHOD: a quantitative cross-sectional study that used the Safety Attitudes Questionnaire was conducted between August and September 2013. The study analyzed 33 professional surveys. Statistical data analysis used descriptive and inferential statistics. RESULTS: among the dimensions analyzed, only "job satisfaction" reached a mean score above 75, considered positive in terms of patient safety culture. CONCLUSION: the dimensions of safety culture present in the survey have to be valued by professionals and managers to allow safe patient care. PMID- 26676439 TI - Validation of newborn positioning protocol in Intensive Care Unit. AB - RESEARCH OBJECTIVE: to verify the positioning indications of newborn sand build a standard operating procedure protocol for newborn positioning in Neonatal Intensive Care Unit (NICU). METHOD: for protocol validation, the Delphi technique was used ,in which expert nurses in the field reviewed the proposed procedure. RESULTS: we present the results of this validation in a protocol form, to contribute to the discussion about newborn positioning in NICU and standardization of nursing care related to positioning. We evaluated ten indicators, in which there was agreementof100.0% in seven, and of80% in three, above the 60% recommended by the validation technique. CONCLUSION: given the importance of newborn positioning in NICU for its neuromuscular development, this study contributes to the adoption of an evidence-based practice for nursing. PMID- 26676440 TI - Fluid and dietary restriction's efficacy on chronic kidney disease patients in hemodialysis. AB - OBJECTIVE: to identify self-care measures to manage fluid and dietary restrictions and assess their effectiveness. METHOD: descriptive-correlational study and cluster analysis with 254 chronic renal failure patients on regular hemodialysis program, handled by hemodiafiltration. We evaluated the effectiveness of self-care by interdialytic weight gain (IWG) and by potassium and phosphorus serum pre-dialysis serum levels. RESULTS: several self-care measures were significantly correlated with a lower IWG and a lower level of pre dialysis phosphorus. Patients most often use measures to reduce salt consumption than measures to restrict potassium and dietary phosphorus. The spouse provides important support dietary management. Subjects who use more often the self-care measure are mostly female, are older, less IWG and have a higher Kt/V. CONCLUSION: these results can contribute to the nursing educational support. PMID- 26676441 TI - Gait speed and cognitive score in elderly users of the primary care service. AB - OBJECTIVE: to investigate the association between gait speed and the cognitive score of elderly patients enrolled in a Basic Health Unit. METHOD: a quantitative cross-sectional study with 203 elderly, a sample calculated based on the estimated population proportion. Data were collected using a sociodemographic and clinical questionnaire, gait speed test (GS) and the Mini Mental State Examination (MMSE). RESULTS: the illiterate patients had a mean MMSE=19.33(+/ 3.7) and GS = 0.76m/s (+/-0.3); those with low/medium education had a MMSE = 25.43(+/-2.8) and GS = 0.92m/s (+/-0.2); and the elderly with higher education had a MMSE = 27.33(+/-2.9) and GS=1.12m/s (+/-0.3).There was a weak correlation (R2=00354) between gait speed and cognitive score, with statistical significance (Prob>F = 0.0072) and a positive linear trend. CONCLUSION: the better cognitive score the higher the gait speed; the illiterate elderly were those with lower gait speed, thereby indicating a poorer physical performance. PMID- 26676442 TI - Low birth weight in a municipality in the southeast region of Brazil. AB - OBJECTIVE: to identify the prevalence of low birth weight in the city of Sao Paulo. METHOD: epidemiological cross-sectional study with data collected by means of the Brazilian Live Birth Information System related to births occurred in the city of Sao Paulo between 2007 and 2013. Maternal, gestational, childbirth, and neonatal variables were analyzed descriptively and by association. RESULTS: 9.65% (1,342,655) of live births were underweight (mean of 3234.55 grams in the term group and 2312.17 in the pre-term group) with a mean maternal age of 27.53 years old. The risk factors identified include maternal age, not having a partner, low maternal level of education, other race rather than white, pre-term pregnancy, multiple births, low number of prenatal check-ups, and cesarean delivery. CONCLUSION: knowledge of this evidence favors planning the care provided by defining strategies to reduce it and consequently improve maternal and infant health care. PMID- 26676443 TI - Concept of family insufficiency in the aged: critical literature analysis. AB - OBJECTIVE: to identify the attributes of the "family insufficiency" concept of the aged in the literature. METHOD: critical literature analysis. RESULTS: family insufficiency is characterized as a complex process of psychosocial interaction, founded mainly on low social support of the aged and impaired family ties. Its antecedents are found in contemporary transformations within the family system, intergenerational conflicts, impaired family relationships and social vulnerability of the family. The consequences of family insufficiency include social vulnerability of the aged, decline of psychological and functional health, lower quality of life and unsuccessful aging. An original theoretical proposal was elaborated for the concept of family insufficiency in the elderly, with the identification of its attributes, antecedents and consequences. CONCLUSION: the findings of this study constitute a theoretical advancement in the Family Insufficiency Syndrome in elderly people and provide data for future field research in developing the concept. PMID- 26676444 TI - Professional Master's Degree: potential contribution to Advanced Practice Nursing. AB - A reflection articleabout the contribution of Master's Degree Programs in Advanced Practice Nursing and the Universal Health Coverage and the Universal Health Access, topicsthat have been discussed by the Pan American Health Organization, and which the Brazilian Nursingrequires not just appropriate, but further studyto reflect in order to define directions for our profession. PMID- 26676445 TI - Salivary IgA and IgG antibodies to bullous pemphigoid 180 noncollagenous domain 16a as diagnostic biomarkers in mucous membrane pemphigoid. AB - BACKGROUND: Mucous membrane pemphigoid (MMP) is an uncommon mucocutaneous immunobullous disorder. Use of saliva for diagnosis by enzyme-linked immunosorbent assay (ELISA) using the noncollagenous (NC) domain 16a of bullous pemphigoid antigen II (BP180) is not well described. OBJECTIVE: To establish whether whole or parotid saliva is a suitable alternative to serum for diagnosis of MMP. METHODS: Precoated BP180-NC16a ELISA plates were used to test serum, and whole and parotid saliva for IgG, IgA and secretory IgA antibodies. Patients with MMP (n = 64) provided matched serum and whole saliva. In addition 18 of the MMP patients also provided matched parotid saliva. Healthy controls (n = 50) provided matched serum and whole saliva and 6 of these additionally provided matched parotid saliva. An additional 16 disease controls provided matched serum, and whole and parotid saliva. RESULTS: In whole saliva, IgG antibodies were detected in 11/64 (17%), IgA in 23/64 (36%) and a combined positivity in 29/64 (45%). In parotid saliva, IgA antibodies were found in 8/18 (44%). Serum IgG antibodies were detected in 27/64 (42%), serum IgA antibodies in 18/64 (28%) and a combined positivity in 33/64 (52%). Combined use of serum and saliva increased detection of specific antibodies by 30%. Control samples were all negative (positive predictive value of 100% for all tests). The negative predictive values were 62% for IgA saliva, 65% for IgG serum, 59% for IgA serum and 56% for IgG saliva. CONCLUSIONS: IgG and IgA antibodies may provide a suitable diagnostic marker in MMP. Assay of salivary IgA antibodies to NC16a offers a similar diagnostic predictive value to serum. PMID- 26676447 TI - Bariatric Surgery for Patients With Type 2 Diabetes. PMID- 26676446 TI - Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway. AB - Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis. Notch-1 knockdown cells were established by transfection with Notch-1 small interfering RNA (siRNA). The expression levels of Notch-1 were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. The results of the present study indicated that eupatilin exhibits an anticancer effect on glioma cells. Eupatilin inhibited proliferation, reduced cell invasion and migration, and promoted the apoptosis of glioma cells. Additionally, it suppressed Notch-1 expression. Knockdown of Notch-1 by siRNA contributed to the inhibitory effect of eupatilin on proliferation and invasion of glioma cells. In conclusion, eupatilin had an inhibitory effect on proliferation, invasion and migration, and promoted apoptosis of glioma cells through suppression of the Notch-1 signaling pathway. Therefore, eupatilin may have potential as an effective agent for the treatment of glioma. PMID- 26676448 TI - Erratum to: On the Link between Cognitive Diagnostic Models and Knowledge Space Theory. PMID- 26676450 TI - Editorial: Issues Surrounding the Symptom of Urgency. PMID- 26676449 TI - Use of propranolol for parotid hemangioma. AB - BACKGROUND: Few specific reports have addressed propranolol as a treatment for parotid hemangioma, and its mechanism remains unclear. METHODS: Eighty-seven patients were recruited in this prospective study. Ten patients underwent detailed color Doppler examination. The depths, vessel densities, and resistant indices of 10 lesions were recorded and analyzed before treatment and at 1 and 3 months after treatment. RESULTS: The overall responses were "bad" in 2 cases, "stable" in 4 cases, "good" in 53 cases, and "excellent" in 28 cases. Hemangioma regrowth was observed in 11 cases (12.6%). The parents of 18 patients (20.7%) complained that their children experienced minor discomfort during therapy. The lesion depths, vessel densities, and resistant indices were altered after propranolol treatment. CONCLUSION: Propranolol can significantly reduce the sizes of parotid hemangiomas with minor side effects. Hemodynamic changes might play an important role in the course of propranolol treatment. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1730-E1736, 2016. PMID- 26676451 TI - Synergistic Effect by Co-Administration of Tamsulosin and Solifenacin on Bladder Activity in Rats. AB - OBJECTIVES: We examined the effects of alpha1-adrenoceptor antagonist (tamsulosin hydrochloride) and antimuscarinic agent (solifenacin succinate) alone or in combination on the urinary adenosine triphosphate (ATP) level and cystometric parameters before and after bladder stimulation. METHODS: Female rats were administered tamsulosin hydrochloride (0.5 or 3 ug/kg/h) and/or solifenacin succinate (20 or 100 ug/kg/h) via a subcutaneously implanted osmotic minipump. Rats receiving distilled water were used as control. After 2 weeks, continuous cystometry with physiological saline or 0.1% acetic acid solution was performed. Urinary ATP level was also measured before and after stimulation by 0.1% acetic acid solution. RESULTS: During cystometry with bladder stimulation, the interval between voiding became shorter and the maximum voiding pressure (MVP) became higher in the control group. In the high-dose tamsulosin and solifenacin groups, the inhibition of urinary frequency was observed. The MVP also became higher in the high-dose tamsulosin group, but such a change was not seen in the high-dose solifenacin group. In case of low-dose administration, either agent alone did not inhibit the increase of urinary frequency and MVP due to bladder stimulation. However, co-administration of these ineffective low doses of tamsulosin and solifenacin resulted in the inhibition of urinary frequency. The high-dose or low dose solifenacin group and the co-administration group showed similar inhibition of the increase of urinary ATP after bladder stimulation. CONCLUSION: Tamsulosin may have a different effect on the bladder and/or the neuronal pathways that is unrelated to ATP, so the combination of tamsulosin and solifenacin may synergistically inhibit urinary frequency after bladder stimulation. PMID- 26676452 TI - The Association between Severity of Atherosclerosis and Lower Urinary Tract Function in Male Patients with Lower Urinary Tract Symptoms. AB - OBJECTIVES: The present study was undertaken to investigate the association between the severity of atherosclerosis and lower urinary tract function in male patients with lower urinary tract symptoms. METHODS: Male patients with lower urinary tract symptoms were examined with routine investigation. The severity of atherosclerosis was assessed by ultrasound examination of carotid artery. Patients were divided into two groups: control group and atherosclerosis group. The voiding function and storage function were compared between the two groups. RESULTS: A total of 50 men (69.9 +/- 9.1 years [mean +/- standard deviation]) entered the study. There was no significant difference in age distribution (control group: 68.7 +/- 7.6 years; atherosclerosis group: 72.5 +/- 9.7 years) and prostate volume (control group: 26.5 +/- 17.3 mL; atherosclerosis group: 22.2 +/- 11.0 mL) between the two groups. In the voiding parameters, maximum flow rate in the atherosclerosis group (13.4 +/- 5.5 mL/s, P < 0.05) was significantly lower than that in the control group (16.7 +/- 7.7 mL/s). Postvoid residual urine volume showed no significant difference between the two groups. In the storage parameters, voided volume was significantly reduced in the atherosclerosis group (161.8 +/- 46 mL, P < 0.05), as compared to control group (201.1 +/- 78 mL). Moreover, daytime frequency was 7.13 +/- 3.02 times in the control group, and significantly higher in the atherosclerosis group (8.75 +/- 2.50 times, P < 0.05). CONCLUSION: Development of atherosclerosis impairs both voiding and storage function independently of age, suggesting atherosclerosis leads to lower urinary dysfunction. PMID- 26676453 TI - Comparison of Two Different alpha1-Adrenoceptor Antagonists, Tamsulosin and Silodosin, in the Treatment of Male Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective Randomized Crossover Study. AB - OBJECTIVES: We assessed the efficacy and safety of two alpha1-adrenoceptor antagonists, tamsulosin and silodosin, in the treatment of male lower urinary tract symptoms. METHODS: Men aged 50 years or older who had a total International Prostate Symptom Score (IPSS) of 8 or higher were enrolled in this study. Forty six patients were randomized into two groups. Twenty-three patients were initially prescribed tamsulosin 0.2 mg once daily for 3 months, followed by silodosin 4 mg twice daily for 3 months (group T); the other group of 23 patients were initially prescribed silodosin, followed by tamsulosin (group S). Patients then switched to the alternative treatment after a 1-month clearance period. Evaluations included clinical determination of IPSS, quality-of-life index, maximum flow rate and postvoid residual urine volume before and after treatment. RESULTS: A total of 46 men, 23 in group T and 23 in group S, were treated and 41 (89.1%) completed the treatment. IPSS, quality-of-life index, maximum flow rate and postvoid residual urine volume were significantly improved in both groups after treatment. The changes in the total IPSS from baseline in groups S and T at 3 months were -6.6 and -7.5, respectively. There were no significant differences between the two groups. After taking both medications, 18 patients preferred silodosin, 11 preferred tamsulosin and others felt they had the same effects. Six and none patients experienced adverse events during silodosin and tamsulosin treatment, respectively. CONCLUSION: Two types of alpha1-adrenoceptor antagonists in the same individuals provide similar efficacy. Profiles and difference of each drug should be considered in making treatment choice. PMID- 26676454 TI - Ketamine-Induced Uropathy: A New Clinical Entity Causing Lower Urinary Tract Symptoms. AB - OBJECTIVES: Ketamine abuse can damage the urinary tract and cause lower urinary tract symptoms (LUTS). This report presents our observations and management on urinary tract damage caused by ketamine abuse. METHODS: From November 2006 to February 2009, 20 patients visited Taipei Veterans General Hospital due to ketamine-related lower urinary tract symptoms. We analyzed the clinical presentations, daily ketamine dose, interval between ketamine usage to develop LUTS, urodynamic studies, radiological image findings, cystoscopic and ureterorenoscopic findings, histological findings, urinary ketamine levels and treatment responses. RESULTS: Of these 20 patients, all had moderate to severe LUTS, including frequency, urgency, dysuria and hematuria. The mean daily consumption of ketamine was 3.2 +/- 2.0 g. The mean interval from consumption to the development of LUTS was 12.7 months (range, 2-36 months). Eight patients underwent video urodynamic studies, with a mean cystometric capacity of 70.8 mL. Eight patients had hydronephrosis and six of them underwent ureterorenoscopy. All patients underwent cystoscopy with hydrodistention. Mean bladder capacity under anesthesia was 289.9 mL, and 14 (70%) patients showed significant symptomatic improvement after hydrodistention. Ten patients quit ketamine and nine (90%) experienced symptomatic relief. The response rates of symptomatic improvement to each treatment were 75% (12/16) for oral pentosan polysulfate sodium with prednisolone, 40% (2/5) intravesical instillation of xylocaine and heparin, and 0% (0/2) for intravesical instillation of hyaluronic acid. CONCLUSIONS: Ketamine abuse causes damage to the upper and lower urinary tracts. While ketamine abuse is an illicit drug problem, it is also associated with serious urological damage. PMID- 26676455 TI - Suppressive Effects of Eviprostat, a Phytotherapeutic Agent, on Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated with Brachytherapy. AB - OBJECTIVES: Eviprostat is an anti-oxidant, anti-inflammatory phytotherapeutic agent that is commonly used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia in Japan and Germany. Prostate cancer patients treated with brachytherapy generally have complaints of LUTS for several months postoperatively. METHODS: We investigated the protective effects of Eviprostat against the development of LUTS in 37 patients, who had received (125) I prostate brachytherapy as monotherapy. These patients were divided into two groups, an Eviprostat-treated group (n = 18) and an untreated control (n = 19), whose background had no significant difference. The group treated with Eviprostat was prophylactically medicated from 3 weeks preoperatively until 3 months postoperatively. Symptom scores and quality of life for urination were evaluated according to the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) on preoperative day 1, and postoperative months 1, 3 and 6. RESULTS: Both the scores of IPSS and the levels of quality of life in EPIC were significantly worse at 1 month postoperatively compared to the pretreatment baseline, and thereafter progressively improved in both groups. Eviprostat-treated patients showed significantly better recovery compared to Eviprostat-untreated control at 6 months postoperatively, with respect to urinary summary score, urinary function and urinary irritation/obstruction subscales in EPIC. Moreover, the feeling of incomplete emptying in IPSS and the urinary irritation/obstruction subscale in EPIC were significantly improved at 3 months postoperatively compared to the peak impairment at 1 month in the Eviprostat treated group. CONCLUSIONS: It is possible that Eviprostat has the potential to ameliorate postoperative LUTS caused by brachytherapy. PMID- 26676456 TI - Difficult Urination Does Not Affect the Successful Outcome after 100U OnabotulinumtoxinA Intravesical Injection in Patients with Idiopathic Detrusor Overactivity. AB - OBJECTIVES: Intravesical injection of onabotulinumtoxinA (i.e. Botox) provides effective treatment for overactive bladder. However, treatment-related adverse events (AEs) remain problems. This study investigated the effect of AEs after onabotulinumtoxinA injection on the success rate for idiopathic detrusor overactivity (IDO). METHODS: A total of 174 patients who received the first single intravesical onabotulinumtoxinA 100U injection for refractory IDO were included. The onabotulinumtoxinA related AEs including acute urinary retention (AUR), large postvoid residual (PVR, >=150 mL), difficult urination, urinary tract infection, gross hematuria and general weakness were recorded. The success rate was determined based on patient perception of bladder condition improved by two scales. The short-term (3 months) and long-term (up to 24 months) success rates were analyzed according to the occurrence of these AEs. RESULTS: A successful outcome was reported by 138 (79.3%) patients at 3 months. AUR occurred in 12 (6.9%) patients, large PVR developed in 81 (46.6%) and 73 (42%) needed straining to void. Gross hematuria occurred in 17 (9.8%) patients, urinary tract infection developed in 27 (15.5%) and general weakness was noted in 6 (3.4%). The occurrence of AUR did not affect the therapeutic results. Patients having large PVR and difficult urination had a significantly higher success rate at 3 months. Long-term success rates up to 24 months showed no significant difference between patients with and without AEs. CONCLUSIONS: AEs after intravesical 100U onabotulinumtoxinA for IDO were frequently encountered. However, the occurrence of AUR, large PVR or difficult urination did not affect the final therapeutic outcome. PMID- 26676457 TI - Effect of Discontinuation of Tamsulosin in Korean Men with Benign Prostatic Hyperplasia Taking Tamsulosin and Dutasteride: An Open-Label, Prospective, Randomized Pilot Study. AB - OBJECTIVE: This study was conducted to examine the effect of discontinuing tamsulosin in patients with benign prostatic hyperplasia who had been receiving combination therapy with tamsulosin and dutasteride. METHODS: The study sample consisted of 108 men with benign prostatic hyperplasia and lower urinary tract symptoms who visited our urology clinics between April 2008 and December 2010. All were assessed using the International Prostate Symptom Score (IPSS). The patients had IPSS of 8-19 and prostate volumes >=25 mL by transrectal ultrasonography. They were put on tamsulosin and dutasteride, and the efficacy of this regimen was assessed every 12 weeks. After 48 weeks, patients were divided at random into a group continuing to take the same drug combination (group 1) and a group taking only dutasteride 0.5 mg (group 2). RESULTS: Sixty-nine of the original 108 patients completed the study, 36 (52%) in group 1 and 33 (48%) in group 2. The mean age of all patients was 67.96 +/- 7.88 years and mean prostatic volume was 40.45 +/- 12.81 mL. Mean prostate-specific antigen was 3.31 (0.4-9.9) ng/mL at the outset. The IPSS scores of the two groups at first visit, 48 and 72 weeks were, respectively, 14.69 versus 15.85 (P = 0.322), 12.08 versus 12.85 (P = 0.582) and 10.89 versus 11.06 (P = 0.897.) There was a statistically significant difference between the baseline and 72-week IPSS scores in both groups (group 1: P < 0.001, group 2: P < 0.001). CONCLUSION: In patients with moderate IPSS, discontinuing tamsulosin after 48 weeks of combined tamsulosin and dutasteride therapy has no significant effect on outcome. PMID- 26676458 TI - Lower Urinary Tract Function in Spinocerebellar Ataxia 6. AB - OBJECTIVE: To investigate lower urinary tract function in spinocerebellar ataxia type 6 (SCA6). METHODS: We recruited, without bias, nine SCA6 patients with a mean cytosine-adenine-guanine repeat length of 24.3 (21-26, normal <18). They were four men, five women; mean age 58.6 years; mean disease duration 8.2 years. We performed a urinary symptom questionnaire and a urodynamics. RESULTS: Urinary symptoms were observed in five of nine patients (56%) and urinary frequency in three of nine patients (33%), and none had urinary retention. Urodynamic abnormalities included detrusor overactivity in one (11%) and weak detrusor on voiding in two, but none had postvoid residual urine. Sphincter electromyography revealed, while mild in degree, neurogenic change in five of the eight patients (63%) on whom the test was performed. CONCLUSION: We observed urinary frequency in 33%; detrusor overactivity in only 11%; and neurogenic change in the sphincter electromyography in 63% of our nine SCA6 patients. These findings might be relevant to the cerebellar and spinal cord pathologies of this disease. PMID- 26676459 TI - Correlations among Lower Urinary Tract Symptoms, Bother, and Quality of Life in Patients with Benign Prostatic Hyperplasia and Associated Fluctuations with Tamsulosin Administration. AB - OBJECTIVES: To estimate correlations among lower urinary tract symptoms (LUTS), bother, and quality of life (QOL) and assess fluctuations in these parameters after alpha1-blocker administration in patients with benign prostatic hyperplasia (BPH). METHODS: Untreated BPH patients with international prostate symptom scores (IPSS) >= 8 and IPSS-QOL scores >= 2 were administered tamsulosin at 0.2 mg/day for 4 weeks in a prospective multicenter study. We subsequently estimated the IPSS, bother score for each IPSS item, BPH impact index (BII), and IPSS-QOL score before and 4 weeks after tamsulosin administration. We also analyzed the LUTS that might strongly influence QOL by using a path analysis model. RESULTS: Analyzable data were obtained from 198 of the 257 patients enrolled. The IPSS were highest for LUTS such as slow stream, followed by increased daytime frequency and nocturia. The bother score was highest for slow stream, followed by nocturia. We observed dissociations between IPSS and bother scores for both urgency and nocturia. After tamsulosin administration, total and individual IPSS, total and individual bother scores, total and individual BII scores, and IPSS-QOL score demonstrated significant improvements. Path analysis showed that physical discomfort and bothersomeness were BII items that strongly influenced QOL. Furthermore, feeling of incomplete emptying, urgency, and slow stream were LUTS that strongly influenced QOL. CONCLUSION: Tamsulosin administration improved patient QOL by possible mechanisms via improvement in subjective symptoms and bother. The LUTS that strongly influenced QOL comprised feeling of incomplete emptying, urgency, and slow stream. PMID- 26676460 TI - Novel Therapy with Intravesical Liposomes for Ulcerative Interstitial Cystitis/Painful Bladder Syndrome. AB - OBJECTIVES: A Federal Drug Administration-approved, compassionate-use, investigational new drug single-subject trial was conducted to evaluate the safety and clinical outcomes of intravesical instillation of liposomes in a woman with ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: After obtaining informed consent, the 48-year-old woman, diagnosed with ulcerative IC/PBS, received four weekly instillations of intravesical liposomes. Subsequently she was evaluated for 8 weeks post bladder instillation. RESULTS: No side effects or adverse events were reported during the 12 week study period. Voids per day decreased from a baseline of 18 voids per 24 h to 11.3 voids per 24 h at week 3, and 12.6 voids per 24 h at 8 weeks after final instillation. Urgency score also decreased from a pre-instillation mean of 1.75 (out of 10) to 1.07 8 weeks after the final instillation. Bladder ulcers noted by cystoscopy at baseline were absent at the 8 weeks post-treatment and no evidence of bladder inflammation was noted. CONCLUSION: Intravesical liposome instillation is minimally invasive and presents an appealing new treatment for IC/PBS. Prospective trials are needed to assess intravesical liposomes for IC/PBS. PMID- 26676461 TI - Implicit solvent coarse-grained model of polyamidoamine dendrimers: Role of generation and pH. AB - Highly branched polymers such as polyamidoamine (PAMAM) dendrimers are promising macromolecules in the realm of nanobiotechnology due to their high surface coverage of tunable functional groups. Modeling efforts of PAMAM can provide structural and morphological properties, but the inclusion of solvents and the exponential growth of atoms with generations make atomistic simulations computationally expensive. We apply an implicit solvent coarse-grained model, called the Dry Martini force field, to PAMAM dendrimers. The reduced number of particles and the absence of a solvent allow the capture of longer spatiotemporal scales. This study characterizes PAMAM dendrimers of generations one through seven in acidic, neutral, and basic pH environments. Comparison with existing literature, both experimental and theoretical, is done using measurements of the radius of gyration, moment of inertia, radial distributions, and scaling exponents. Additionally, ion coordination distributions are studied to provide insight into the effects of interior and exterior protonation on counter ions. This model serves as a starting point for future designs of larger functionalized dendrimers. PMID- 26676462 TI - Bismuth Undecahydro-closo-dodecaborane: A Retainable Intermediate of B-H Bond Activation by Bismuth(III) Cations. AB - The [B12 H12](2-) anion shows an extensive substitutional chemistry based on its three-dimensional aromaticity. The replacement of functional groups can be attained by electrophilically induced substitution caused by Bronsted or Lewis acidic electrophiles (e.g. Pt(2+)). Until now, it was impossible to structurally characterize a metal-substituted [B12 H12](2-) cage. When an aqueous solution containing both Bi(3+) cations and [B12 H12](2-) anions was heated, the charge neutral bismuth undecahydro-closo-dodecaborane BiB12 H11 was obtained, representing a new class of metalated [B12 H12](2-) clusters. The title compound was characterized by single-crystal X-ray diffraction and NMR spectroscopic methods. Compared to the typical B-H bond, the short B-Bi single bond (230 pm) exhibits inverted polarity. PMID- 26676463 TI - Black medicine: an observational study of doctors' coffee purchasing patterns at work. AB - OBJECTIVE: To evaluate doctors' coffee consumption at work and differences between specialties. DESIGN: Single centre retrospective cohort study. SETTING: Large teaching hospital in Switzerland. PARTICIPANTS: 766 qualified doctors (425 men, 341 women) from all medical specialties (201 internal medicine, 76 general surgery, 67 anaesthetics, 54 radiology, 48 orthopaedics, 43 gynaecology, 36 neurology, 23 neurosurgery, 96 other specialties). DATA SOURCE: Staff purchasing history from staff canteens' electronic payment system linked to separate anonymised personal data from the human resource database. MAIN OUTCOME MEASURE: Numbers of coffees purchased per person per year. RESULTS: 84% (644) of doctors purchased coffee at one of the hospital canteens. 70 772 coffees were consumed by doctors in 2014. There was a significant association between specialty and yearly coffee purchasing (F=12.45; P<0.01). On average orthopaedic surgeons purchased the most coffee per person per year (mean 189, SD 136) followed by radiologists (177, SD 191) and general surgeons (167, SD 138). Anaesthetists purchased the least coffee (39, SD 48). Male doctors bought significantly more coffees per person per year (128 (SD 140) v 86 (SD 86), t=-4.66, P<0.01) and twice as many espressos as female doctors (mean 27 (SD 46) v 10 (SD 19), t=-6.54, P<0.01). Hierarchical position was associated with coffee purchasing (F=4.55; P=0.04). Senior consultants (>5 years' experience) bought most coffees per person per year (140, SD 169) and junior doctors and registrars bought fewest (95, SD 85). Propensity of buying rounds also increased with hierarchical position (chi(2)=556.24; P<0.01), with heads of departments buying more rounds than junior doctors (30% v 15%). CONCLUSIONS: Doctors commonly use coffee as a stimulant. Substantial variation exists between specialties. Surgeons drink notably more coffee than physicians, with orthopaedic surgeons consuming the greatest amount in the communal cafeteria setting, though this might reflect social tendencies rather than caffeine dependency. Hierarchical position is positively correlated with coffee consumption and generosity with regard to buying rounds of coffee. PMID- 26676465 TI - Subgrouping fibromyalgia patients according to response to therapeutic interventions: a new concept for a disease with low treatment-response rates. PMID- 26676466 TI - Authors' correction for Euro Surveill. 2015;20(45). PMID- 26676464 TI - PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer. AB - We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1), and detected PIK3R1 coding protein (p85alpha) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85alpha overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR-21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85alpha, accompanied by decreased p-AKT level. Besides, antimiR 21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85alpha downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85alpha downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS, which may require more aggressive treatment. PMID- 26676467 TI - Flexoelectric MEMS: towards an electromechanical strain diode. AB - Piezoelectricity and flexoelectricity are two independent but not incompatible forms of electromechanical response exhibited by nanoscale ferroelectrics. Here, we show that flexoelectricity can either enhance or suppress the piezoelectric response of the cantilever depending on the ferroelectric polarity and lead to a diode-like asymmetric (two-state) electromechanical response. PMID- 26676468 TI - Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling. AB - Endothelial progenitor cells (EPCs) can form new vessels through differentiation into endothelial cells (ECs), thus being important in the prevention of hypoxia/ischemia. Apelin can activate different signaling pathways through its receptor, APLNR, which regulate diverse biological functions, including cardiovascular function. However, the molecular mechanism by which Apelin mediates hypoxia-induced EPCs proliferation remain to be fully elucidated. The present study aimed to determine the role of Apelin/APLNR signaling in hypoxia induced proliferation of EPCs. MTT assay was used to determine cell proliferation. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis were conducted to examine mRNA and protein expression. It was revealed that hypoxia promoted the proliferation of the EPCs. Further investigation demonstrated that hypoxia promoted the expression levels of hypoxia inducible factor (HIF)-1alpha, Apelin and APLNR in the EPCs. In addition, upregulation of Apelin or APLNR promoted the hypoxia-induced proliferation of the EPCs, while knockdown of Apelin or APLNR by small interfering RNA suppressed the hypoxia-induced proliferation of the EPCs, suggesting that the Apelin/APLNR axis is involved in hypoxia-induced proliferation of EPCs. Furthermore, pretreatment of the EPCs with SB-239063 or PD98059, two inhibitors of mitogen-activated protein kinase (MAPK), eliminated the Apelin upregulation-induced EPC proliferation, suggesting that MAPK signaling is a downstream effecter of Apelin/APLNR in EPCs. Therefore, the findings of the present study indicated that the production of HIF-1alpha, induced by hypoxia, activated the Apelin/APLNR and the downstream MAPK signaling pathways, leading to upregulated proliferation of the EPCs. These findings suggested that Apelin/APLNR signaling may be used as a potential therapeutic target for hypoxic/ischemic injury. PMID- 26676469 TI - Gastrointestinal: Severe de novo stricture formation following biodegradable esophageal stent. PMID- 26676470 TI - Can Ebola virus become endemic in the human population? PMID- 26676471 TI - [Operative medicine in Mozart's operas - a contribution to gender equality in medicine]. PMID- 26676472 TI - [Mesmer's time in Vienna]. PMID- 26676473 TI - [Witch hunt and hypotheses loss]. AB - At this time randomized controlled studies (RCT) in clinical trials usually have high quality. But this quality is only true for the included patients (intrinsic validity). It is common to generalize the results to more or less similar patients. This inductive method is prohibited in epistemology what is known for 250 years (D Hume, K R Popper). Therefore the external validity for the data of RCT is low. To solve this problem additional clinical and pathophysiological based data are necessary to generalize the results. Unfortunately RCT show less quality in their premises. This is partly due to the influence of the pharmaceutical industry. A loss of universality of the hypothesis for RCT decreases basically the extrinsic validity. The articles describe this problem with examples. PMID- 26676474 TI - [On the Awarding of the First Nobel Prize for Physiology or Medicine to Emil von Behring]. AB - In his will of 1895, the Swedish inventor Alfred Nobel laid the foundation for prizes in physics, chemistry, physiology or medicine, literature, and peace to those who had "conferred the greatest benefit on mankind" during the last year. The Nobel Prize is today widely considered as the most prestigious international symbol of scientific excellence, but it still is an exciting research question how it gained such prestige. Drawing on files from the Emil von Behring Archive in Marburg, Germany, and the Archive of the Nobel Assembly for Physiology or Medicine in Stockholm this essay aims at shedding light on why the first Nobel Prize for Physiology or Medicine in 1901 was awarded the German immunologist Emil von Behring, and how this decision was viewed at that time. This study is part of a research project that explores mechanisms leading to scientific recognition by using the example of the Nobel Prize for Physiology or Medicine. PMID- 26676475 TI - [The last days of Albert Schweitzer]. AB - Schweitzer was one of the leading physicians of the last century. He overcame not only the boundaries of humanities and natural sciences, but also the boundaries of Europe and Africa. He has become a symbol of humanity. But the person of Albert Schweitzer was almost in danger of disappearing behind it. "My hair starts to turn gray. My body begins to feel the exertions I have undertaken, and the burden of the years". This is how the 56-year-old Schweitzer ended his autobiography "Out of my life and thought" in 1931. Even 50 years after Schweitzer's death in 1965, there is still no coherent scientific reappraisal of his work. Part of the posthumous manuscripts was published in recent years in a critical edition, including first biographies that are no longer considered as hagiography, as they would have been in the contemporary literature. The legacy, however, is scattered. Much of the correspondence and the library are located in Schweitzer's former house in Gunsbach in Alsace. The manuscripts are mainly stored in the Central Library Zurich, but also in the Syracuse University New York, while the personal bequest is in the hands of his family or collectors. This presentation is part of a biographical approach and depicts the last weeks in the life of Albert Schweitzer. PMID- 26676476 TI - [God forbid doctors have such whimsical patients ]. PMID- 26676477 TI - [Helpless helpers? Health and disease of physicians in historical perspective]. AB - Seen from a historical perspective the health and illness of a physician is not at all his private matter; they have an impact on his relationship with his patients and the public. Drawing on sources from Graeco-Roman times up to now information referring to this subject is scarce and heterogeneous. However, it is possible to differentiate between three main concepts encompassing various periods: In those reaching approximately until 1700 the physician's personal health and recovery were his credentials of his art of healing. In the following 250 years he increasingly stylized himself as a victim in the service of his patients and science. After 1970 helpless helpers are threatened by mental illness. PMID- 26676478 TI - [From phenotype to genotype: a glimpse behind the scenes of an unending story]. AB - Mendelian conditions direct attention at basic mechanisms. In the 1990's DNA sequencing allowed elucidating such conditions. We embarked on an unexpected adventure to study a monogenic autosomal-dominant form of hypertension causing also a specific form of short fingers. The gene locus caused a 50 mmHg increase in blood pressure at age of 50. Our clinically based group stumbled to the finish line after 20 years of study. We remained together and proudly persevered. Our findings could be relevant for essential hypertension. PMID- 26676479 TI - A Rapid and Cheap Methodology for CRISPR/Cas9 Zebrafish Mutant Screening. AB - The introduction of new genome editing tools such as ZFNs, TALENs and, more recently, the CRISPR/Cas9 system, has greatly expanded the ability to knock-out genes in different animal models, including zebrafish. However, time and costs required for the screening of a huge number of animals, aimed to identify first founder fishes (F0), and then carriers (F1) are still a bottleneck. Currently, high-resolution melting (HRM) analysis is the most efficient technology for large scale InDels detection, but the very expensive equipment demanded for its application may represent a limitation for research laboratories. Here, we propose a rapid and cheap method for high-throughput genotyping that displays efficiency rate similar to the HRM. In fact, using a common ViiATM7 real-time PCR system and optimizing the parameters of the melting analysis, we demonstrated that it is possible to discriminate between the mutant and the wild type melting curves. Due to its simplicity, rapidity and cheapness, our method can be used as a preliminary one-step approach for massive screening, in order to restrict the scope at a limited number of embryos and to focus merely on them for the next sequencing step, necessary for the exact sequence identification of the induced mutation. Moreover, thanks to its versatility, this simple approach can be readily adapted to the detection of any kind of genome editing approach directed to genes or regulatory regions and can be applied to many other animal models. PMID- 26676480 TI - Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors. AB - A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 MUM to 20 MUM. Two of the conjugates RSV 1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells. PMID- 26676481 TI - Microbial community, and biochemical and physiological properties of Korean traditional black raspberry (Robus coreanus Miquel) vinegar. AB - BACKGROUND: The aim of this study was to elucidate the changes in microbial community and biochemical and physiological properties of traditional Muju black raspberry (Robus coreanus Miquel) vinegar (TMBV) during fermentation by culture independent methods. RESULTS: During vinegar fermentation, ethanol produced up to 120 g L(-1) until day 35, with continuously increasing yeast concentration to a total of log 7.6 CFU mL(-1) . After day 35, acetic acid bacteria (AAB) concentrations rose to log 5.8 CFU mL(-1) until day 144. Denaturing gradient gel electrophoresis analysis showed that Saccharomyces cerevisiae was detected until day 87 of the fermentation, at which point Acetobacter pasteurianus gradually took over as the dominant species. Total sugar was reduced to 6.6 degrees Brix and total acidity produced up to 44 g L(-1) . CONCLUSION: In this study, we established the physicochemical analysis and growth dynamics of yeast and AAB during alcoholic and acetic acid fermentation of black raspberry by a traditional method. Overall, S. cerevisiae and A. pasteurianus species appeared to dominate the TMBV fermentation. In conclusion, this study demonstrated a suitable fermentation system for TMBV by the static surface method. (c) 2015 Society of Chemical Industry. PMID- 26676482 TI - Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions. AB - Human umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDH(hi) ) stimulate islet regeneration after transplantation into mice with streptozotocin-induced beta cell deletion. However, ALDH(hi) cells represent a rare progenitor subset and widespread use of UCB ALDH(hi) cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDH(hi) cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, kinetic analyses over 9 days revealed the frequency of ALDH(hi) cells diminished as culture time progressed such that total ALDH(hi) cell number was maximal (increased 3-fold) at day 6. Subsequently, day 6 expanded cells (bulk cells) were sorted after culture to reselect differentiated progeny with low ALDH-activity (ALDH(lo) subset) from less differentiated progeny with high ALDH-activity (ALDH(hi) subset). The ALDH(hi) subset retained primitive cell surface marker coexpression (32.0% +/- 7.0% CD34(+) /CD38(-) cells, 37.0% +/- 6.9% CD34(+) /CD133(+) cells), and demonstrated increased hematopoietic colony forming cell function compared with the ALDH(lo) subset. Notably, bulk cells or ALDH(lo) cells did not possess the functional capacity to lower hyperglycemia after transplantation into streptozotocin-treated NOD/SCID mice. However, transplantation of the repurified ALDH(hi) subset significantly reduced hyperglycemia, improved glucose tolerance, and increased islet-associated cell proliferation and capillary formation. Thus, expansion and delivery of reselected UCB cells that retain high ALDH-activity after short-term culture represents an improved strategy for the development of cellular therapies to enhance islet regeneration in situ. PMID- 26676483 TI - Topographic matching of distal radius and proximal fibula articular surface for distal radius osteoarticular reconstruction. AB - During osteoarticular reconstruction of the distal radius with the proximal fibula, congruity between the two articular surfaces is an important factor in determining the quality of the outcome. In this study, a three-dimensional model and a coordinate transformation algorithm were developed on computed tomography scanning. Articular surface matching was performed and parameters for the optimal position were determined quantitatively. The mean radii of best-fit spheres of the articular surfaces of the distal radius and proximal fibula were compared quantitatively. The radial inclination and volar tilt following reconstruction by an ipsilateral fibula graft, rather than the contralateral, best resembles the values of the native distal radius. Additionally, the ipsilateral fibula graft reconstructed a larger proportion of the distal radius articular surface than did the contralateral. The ipsilateral proximal fibula graft provides a better match for the reconstruction of the distal radius articular surface than the contralateral, and the optimal position for graft placement is quantitatively determined. PMID- 26676485 TI - A tip for stabilization of the amputated part in digital replantation. PMID- 26676484 TI - Outcomes of release of the entire A4 pulley after flexor tendon repairs in zone 2A followed by early active mobilization. AB - We report the outcomes of repair of the flexor digitorum profundus tendon in zone 2a in 22 fingers. The tendon was repaired with a six-strand repair method and the A4 pulley was completely released. Release of the C2 pulley combined with the A4 pulley was necessary in 12 fingers, nine fingers underwent a complete release of the A3, C2, and A4 pulleys, and one finger underwent a release of the C1, A3, C2, and A4 pulleys. The mean total active motion of the three finger joints was 234 degrees at 5 to 12 months of follow-up. No bowstringing was noted in these fingers. The good and excellent recovery of active digital motion was in 20 (91%) out of 22 fingers according to Strickland's criteria or Tang's criteria. Our results suggest that release of the A3, C2, and A4 pulleys makes the repair surgery easier and does not cause tendon bowstringing. PMID- 26676486 TI - Bites and stings from venomous animals: a neglected Brazilian tropical disease. PMID- 26676487 TI - Clinical update on scorpion envenoming. AB - Scorpion stings are currently the leading cause of venom-related injury to humans in Brazil and are a significant public health problem globally. Only scorpions of the Tityus genus are of medical importance in Brazil, and Tityus serrulatus is responsible for the most serious envenomations and deaths. The toxic effects of scorpion envenomation are due to a massive release of sympathetic and parasympathetic neurotransmitters; the severity is related to cardiac and hemodynamic changes, with cardiogenic shock and pulmonary edema contributing to the main causes of death. The pathophysiology of cardiac involvement has been discussed for decades and has been attributed to adrenergic discharge and a possible toxic effect of venom on the myocardium, while acute pulmonary edema may have a cardiogenic and/or non-cardiogenic origin. Currently, the clinical data point to catecholamine excess as the cause for reversible scorpion cardiomyopathy . These data include electrocardiographic changes, profiling of cardiac enzymes and troponin I, echocardiographic data with global or regional left ventricle dysfunction, and myocardial perfusion alterations compatible with spasm in the coronary microcirculation. Furthermore, recent data on cardiac magnetic resonance imaging findings, which are similar to those observed for stress-induced cardiomyopathy, have also been linked to catecholamine excess. The efficiency of antivenom serum treatment is controversial in the literature. Our experience in Brazil is that the management of patients with systemic manifestations of scorpion stings is based on three approaches, all of which are extremely important. These include symptomatic treatment, antivenom serum, and cardiorespiratory support. PMID- 26676488 TI - Venomous and poisonous arthropods: identification, clinical manifestations of envenomation, and treatments used in human injuries. AB - This review presents the main species of venomous and poisonous arthropods, with commentary on the clinical manifestations provoked by the toxins and therapeutic measures used to treat human envenomations. The groups of arthopods discussed include the class Arachnida (spiders and scorpions, which are responsible for many injuries reported worldwide, including Brazil); the subphylum Myriapoda, with the classes Chilopoda and Diplopoda (centipedes and millipedes); and the subphylum Hexapoda, with the class Insecta and the orders Coleoptera (beetles), Hemiptera (stink bugs, giant water bugs, and cicadas), Hymenoptera (ants, wasps, and bees), and Lepidoptera (butterflies and moths). PMID- 26676489 TI - Evaluation of the World Health Organization 2009 classification of dengue severity in autopsied individuals, during the epidemics of 2011 and 2012 in Brazil. AB - INTRODUCTION: The dengue classification proposed by the World Health Organization (WHO) in 2009 is considered more sensitive than the classification proposed by the WHO in 1997. However, no study has assessed the ability of the WHO 2009 classification to identify dengue deaths among autopsied individuals suspected of having dengue. In the present study, we evaluated the ability of the WHO 2009 classification to identify dengue deaths among autopsied individuals suspected of having dengue in Northeast Brazil, where the disease is endemic. METHODS: This retrospective study included 121 autopsied individuals suspected of having dengue in Northeast Brazil during the epidemics of 2011 and 2012. All the autopsied individuals included in this study were confirmed to have dengue based on the findings of laboratory examinations. RESULTS: The median age of the autopsied individuals was 34 years (range, 1 month to 93 years), and 54.5% of the individuals were males. According to the WHO 1997 classification, 9.1% (11/121) of the cases were classified as dengue hemorrhagic fever (DHF) and 3.3% (4/121) as dengue shock syndrome. The remaining 87.6% (106/121) of the cases were classified as dengue with complications. According to the 2009 classification, 100% (121/121) of the cases were classified as severe dengue. The absence of plasma leakage (58.5%) and platelet counts <100,000/mm3 (47.2%) were the most frequent reasons for the inability to classify cases as DHF. CONCLUSIONS: The WHO 2009 classification is more sensitive than the WHO 1997 classification for identifying dengue deaths among autopsied individuals suspected of having dengue. PMID- 26676490 TI - Incidence of hepatitis C in Brazil. AB - INTRODUCTION: Hepatitis C is a public health problem of global dimensions, affecting approximately 200 million people worldwide. The main objective of this study was to estimate the incidence rate of hepatitis C in Brazil during the period between 2001 and 2012. METHODS: An epidemiological, temporal, and descriptive study was performed using data from the Information System for Reportable Diseases. RESULTS: Between 2001 and 2012, a total of 151,056 hepatitis C cases were recorded, accounting for 30.3% of all hepatitis notifications in Brazil. The average gross coefficient for the analysis period was 6.7 new cases per 100,000 inhabitants. The regions with the highest rates were the Southeast region (8.7 new cases/100,000 inhabitants) and the South (13.9 new cases/100,000 inhabitants). There was a predominance of men with respect to the incidence rate (8.0 new cases/100,000 inhabitants) compared to women (5.5 new cases/100,000 inhabitants). Injection drug use was the most common source of infection, and members of the white race, residents of urban areas, and those aged 60 to 64 years had the highest incidences. CONCLUSIONS: Over the last 10 years, the incidence of hepatitis C in Brazil has increased, mainly in the South and Southeast. The adoption of fast, accurate diagnostic methods, together with epidemiological awareness, can facilitate early intervention measures for adequate control of the disease. PMID- 26676491 TI - Epidemiological study of hepatitis B and C in a municipality with rural characteristics: Cassia dos Coqueiros, State of Sao Paulo, Brazil. AB - INTRODUCTION: Hepatitis B and C viral infections remain an important cause of global morbidity and mortality. Studies have been conducted in population groups of large cities, leaving gaps in the knowledge regarding the situation in small municipalities. We aimed to measure the prevalence of hepatitis B and C markers and presence of infection-associated factors. METHODS: All inhabitants of Cassia dos Coqueiros aged >=18 years who agreed to participate in the research were included. We collected blood as well as information via a questionnaire between March 2011 and December 2013. Univariate and multivariate analyses were conducted. RESULTS: Among the 1,001 participants, 41 (4.1%) participants had a serological profile of hepatitis B viral exposure, and only one (0.1%) participant was considered a virus carrier. The frequency of isolated antibody to hepatitis B virus surface antigen (anti-HBs) markers was 17.8% for the overall population. In the multivariate analysis, hepatitis B virus (HBV) infection was associated with age, birth outside the State of Sao Paulo, history of hepatitis, >=2 sexual partners in the last 6 months, and tattoos. Four (0.4%) participants had a serological profile of hepatitis C viral exposure. However, after confirmation using viral ribonucleic acid (RNA) evaluation, only one (0.1%) individual remained positive. CONCLUSIONS: The positivity rates for hepatitis B and C were low, despite greater sexual freedom and the recent emergence of illicit drugs, as observed by the health personnel working in Cassia dos Coqueiros. PMID- 26676492 TI - Can body traits, other than wings, reflect the flight ability of Triatominae bugs? AB - INTRODUCTION: Insects of the subfamily Triatominae are vectors of Trypanosoma cruzi , the Chagas disease parasite, and their flying behavior has epidemiological importance. The flying capacity is strikingly different across and within Triatominae species, as well as between sexes or individuals. Many Triatoma infestans individuals have wings but no flying muscles. In other Triatominae species, no clear relationships were found between wing length and flying behavior. If wing presence or size is not reflective of the flying behavior, which other parts of the body could be considered as reliable markers of this important function? METHODS: The genus Mepraia has exceptional characteristics with invariably wingless females and wingless or winged males. We calculated the porous surface exposed to odorant molecules to estimate the olfactory capacity of Mepraia spinolai . The head shape and thorax size were estimated using the geometric morphometric approach and traditional morphometric techniques, respectively. RESULTS: Alary polymorphism in M. spinolai was significantly associated with consistent modification of the thorax size, head shape, and notable change in the estimated olfactory capacity. The macropterous individuals had a larger olfactory surface and thorax size and significantly different head shape compared to those of the micropterous individuals. CONCLUSIONS: We concluded that these structural changes could be associated with the flying potential of Triatominae. Thus, morphological attributes not found on wings could help determine the likely flying potential of the bugs. PMID- 26676493 TI - Occurrence and sensitivity profile of extended spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary hospital in Southern Brazil. AB - INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to beta lactam antibiotics is the production of extended spectrum beta-lactamases (ESBLs). The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital Sao Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS: We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%). Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS: In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms. PMID- 26676494 TI - Antimicrobial resistance profiles and oxacillinase genes in carbapenem-resistant Acinetobacter baumannii isolated from hospitalized patients in Santa Catarina, Brazil. AB - INTRODUCTION: Carbapenems are the therapy of choice for treating severe infections caused by the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. We aimed to assess the prevalence and antimicrobial susceptibility profiles of producers of distinct oxacillinases among nosocomial isolates of the A. calcoaceticus-A. baumannii complex in a 249-bed general hospital located in Joinville, Southern Brazil. METHODS: Of the 139 A. baumannii clinical isolates with reduced susceptibility to carbapenems between 2010 and 2013, 118 isolates from varying anatomical sites and hospital sectors were selected for genotypic analysis. Five families of genes encoding oxacillinases, namely blaOXA-23-like, blaOXA-24-like, bla(OXA-51-like), bla(OXA-58-like), and blaOXA-143-like, were investigated by multiplex polymerase chain reaction (PCR). RESULTS: Most (87.3%) isolates simultaneously carried the bla(OXA-23-like) and bla(OXA-51-like) genes, whereas three (2.5%) isolates harbored only blaOXA-51-like ones. The circulation of carbapenem-resistant isolates increased during the study period: from none in 2010, to 22 in 2011, 64 in 2012, and 53 in 2013. CONCLUSIONS: Isolates carrying the bla(OXA-23-like) and bla(OXA-51-like) genes were widely distributed in the hospital investigated. Because of the worsening scenario, the implementation of preventive measures and effective barriers is needed. PMID- 26676495 TI - Chagas disease: morbidity profile in an endemic area of Northeastern Brazil. AB - INTRODUCTION: This study evaluated the clinical forms and manifestation severities of Chagas disease among serologically reactive individuals from Western Rio Grande do Norte (Northeastern Brazil). METHODS: This cross-sectional study included 186 adults who were evaluated using electrocardiography, echocardiography, chest radiography, and contrast radiography of the esophagus and colon. A clinical-epidemiological questionnaire was also used. RESULTS: The indeterminate, cardiac, digestive, and cardiodigestive clinical forms of Chagas disease were diagnosed in 51.6% (96/186), 32.2% (60/186), 8.1% (15/186) and 8.1% (15/186) of the participants, respectively. Heart failure (functional classes I IV) was detected in 7.5% (14/186) of the participants, and 36.4% (24/66), 30.3% (20/66), 15.2% (10/66), 13.6% (9/66), and 4.5% (3/66) of the patients were at stage A, B1, B2, C, and D, respectively. Dilated cardiomyopathy and electrocardiographic changes were detected in 10.2% (19/186) and 48.1% (91/186) of the participants, respectively. Apical aneurysm was diagnosed in 10.8% (20/186) of the participants, and other changes in the segmental myocardial contractility of the left ventricle were diagnosed in 33.9% (63/186) of the participants. Megaesophagus (groups I-IV) was observed in 7% (13/186) of the participants, megacolon (grades 1-3) was detected in 12.9% (24/186) of the participants, and both organs were affected in 29.2% (7/24) of the megacolon cases. CONCLUSIONS: We detected various clinical forms of Chagas disease (including the digestive form). Our findings indicate that clinical symptoms alone may not be sufficient to exclude or confirm cardiac and/or digestive damage, and the number of patients with symptomatic clinical forms may be underestimated. PMID- 26676496 TI - Spatial and spatiotemporal occurrence of human visceral leishmaniasis in Adamantina, State of Sao Paulo, Brazil. AB - INTRODUCTION: Several municipalities of the Western region of the State of Sao Paulo have been affected by human visceral leishmaniasis (HVL), including the City of Adamantina, where the first autochthonous cases occurred in 2004. Therefore, this study aimed to describe the spatial and spatiotemporal occurrence of HVL in Adamantina. METHODS: Secondary data regarding the occurrence of HVL in Adamantina between 2004 and 2011 were used. Incidence, mortality, and case fatality rates were calculated. We used local empirical Bayesian incidence rates to represent the occurrence of the disease in the census sector of the city. The existence of spatial and spatiotemporal clusters of cases was evaluated using scan statistics. In situ observation was performed to assess the socioeconomic and environmental characteristics of the areas with medium and high incidences. RESULTS: Adamantina reported cases in 70% of its census sectors. No differences were observed between sexes. The group aged 0-4 years presented the highest incidence and mortality rates, and the group aged 40-59 years presented the highest fatality rate. We detected a spatiotemporal cluster, which coincided with the commencement of the endemic in the city. CONCLUSIONS: The individuals most affected by the disease were children. The disease was present in areas with better and worse socioeconomic conditions. The use of spatial analysis techniques was important to achieve the study objectives. PMID- 26676497 TI - Diagnosis of latent Mycobacterium tuberculosis infection: tuberculin test versus interferon-gamma release. AB - INTRODUCTION: The treatment of individuals with active tuberculosis (TB) and the identification and treatment of latent tuberculosis infection (LTBI) contacts are the two most important strategies for the control of TB. The objective of this study was compare the performance of tuberculin skin testing (TST) with QuantiFERON-TB Gold In TUBE(r) in the diagnosis of LTBI in contacts of patients with active TB. METHODS: Cross-sectional analytical study with 60 contacts of patients with active pulmonary TB. A blood sample of each contact was taken for interferon-gamma release assay (IGRA) and subsequently performed the TST. A receiver operating characteristic curve was generated to assess the cutoff points and the sensitivity, predictive values, and accuracy were calculated. The agreement between IGRA and TST results was evaluated by Kappa coefficient. RESULTS: Here, 67.9% sensitivity, 84.4% specificity, 79.1% PPV, 75% NPV, and 76.7% accuracy were observed for the 5mm cutoff point. The prevalence of LTBI determined by TST and IGRA was 40% and 46.7%, respectively. CONCLUSIONS: Both QuantiFERON-TB Gold In TUBE(r) and TST showed good performance in LTBI diagnosis. The creation of specific diagnostic methods is necessary for the diagnosis of LTBI with higher sensitivity and specificity, preferably with low cost and not require a return visit for reading because with early treatment of latent forms can prevent active TB. PMID- 26676498 TI - Single-tube nested PCR assay with in-house DNA extraction for Mycobacterium tuberculosis detection in blood and urine. AB - INTRODUCTION: Molecular analyses are auxiliary tools for detecting Koch's bacilli in clinical specimens from patients with suspected tuberculosis (TB). However, there are still no efficient diagnostic tests that combine high sensitivity and specificity and yield rapid results in the detection of TB. This study evaluated single-tube nested polymerase chain reaction (STNPCR) as a molecular diagnostic test with low risk of cross contamination for detecting Mycobacterium tuberculosis in clinical samples. METHODS: Mycobacterium tuberculosis deoxyribonucleic acid (DNA) was detected in blood and urine samples by STNPCR followed by agarose gel electrophoresis. In this system, reaction tubes were not opened between the two stages of PCR (simple and nested). RESULTS: STNPCR demonstrated good accuracy in clinical samples with no cross contamination between microtubes. Sensitivity in blood and urine, analyzed in parallel, was 35% 62% for pulmonary and 41%-72% for extrapulmonary TB. The specificity of STNPCR was 100% in most analyses, depending on the type of clinical sample (blood or urine) and clinical form of disease (pulmonary or extrapulmonary). CONCLUSIONS: STNPCR was effective in detecting TB, especially the extrapulmonary form for which sensitivity was higher, and had the advantage of less invasive sample collection from patients for whom a spontaneous sputum sample was unavailable. With low risk of cross contamination, the STNPCR can be used as an adjunct to conventional methods for diagnosing TB. PMID- 26676499 TI - Risk-benefit assessment of Bacillus Calmette-Guerin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients. AB - INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guerin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS: Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies. PMID- 26676500 TI - Chemical composition and antifungal activity of essential oil from Eucalyptus smithii against dermatophytes. AB - INTRODUCTION: In this study, we evaluated the chemical composition of a commercial sample of essential oil from Eucalyptus smithii R.T. Baker and its antifungal activity against Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 9533, T. mentagrophytes ATCC 11480, T. mentagrophytes ATCC 11481, and Trichophyton rubrum CCT 5507. METHODS: Morphological changes in these fungi after treatment with the oil were determined by scanning electron microscopy (SEM). The antifungal activity of the oil was determined on the basis of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. RESULTS: The compound 1,8-cineole was found to be the predominant component (72.2%) of the essential oil. The MIC values of the oil ranged from 62.5MUg.mL-1 to >1,000MUg.mL-1, and the MFC values of the oil ranged from 125MUg.mL-1 to >1,000MUg.mL-1. SEM analysis showed physical damage and morphological alterations in the fungi exposed to this oil. CONCLUSIONS: We demonstrated the potential of Eucalyptus smithii essential oil as a natural therapeutic agent for the treatment of dermatophytosis. PMID- 26676501 TI - Emergent and re-emergent parasites in HIV-infected children: immunological and socio-environmental conditions that are involved in the transmission of Giardia spp. and Cryptosporidium spp. AB - INTRODUCTION: Emergent and re-emergent waterborne protozoans have become a worldwide public health problem, especially among vulnerable groups. METHODS: This cross-sectional study evaluated 17 HIV-infected children and their families. RESULTS: A high (76.5%) percentage of parasite-infected children was observed, even among children with CD4+ T-cell counts of >200 cells/mm3. Giardia spp., Cryptosporidium spp. and Cyclospora spp. were observed in 41.2% of these children Low income, poor hygiene practices, and co-infection in domestic, peridomestic and scholastic environments were significant sources of these intestinal infections. CONCLUSIONS: Early diagnosis, timely treatment, and socio-educational interventions may improve the health conditions of this vulnerable population. PMID- 26676502 TI - Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women? AB - INTRODUCTION: The human T-lymphotropic virus-1 (HTLV-1) is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS: Plasma levels of triglycerides, total cholesterol, and fractions of HTLV 1-infected individuals of both sexes with different clinical progressions were determined. RESULTS: Elevated levels of triglyceride and very low-density lipoproteins (VLDL) were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02). CONCLUSIONS: Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women. PMID- 26676503 TI - Performance of direct immunofluorescence assay for the detection of human metapneumovirus under clinical laboratory settings. AB - INTRODUCTION: Human metapneumovirus (hMPV) is an emergent human respiratory pathogen. This study aimed to evaluate the performance of direct immunofluorescence (DIF) to detect hMPV in a clinical laboratory setting. METHODS: Nasopharyngeal aspirate samples (448) of children and adults with respiratory illness were used to detect hMPV by using DIF and real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. RESULTS: In all, 36 (8%) samples were positive by DIF and 94 (21%) were positive by qRT-PCR. Direct immunofluorescence specificity was 99% and sensitivity was 38%. CONCLUSIONS: DIF is not very sensitive under clinical laboratory settings. PMID- 26676504 TI - Anopheles darlingi and Anopheles marajoara (Diptera: Culicidae) susceptibility to pyrethroids in an endemic area of the Brazilian Amazon. AB - INTRODUCTION: This study aimed to evaluate the susceptibility of Anopheles darlingi Root (1926) and Anopheles marajoara Galvao & Damasceno (1942) to pyrethroids used by the National Malaria Control Program in Brazil. METHODS: Mosquitoes from Amapa, Brazilian Amazon, were assessed for resistance to cypermethrin, deltamethrin, and alpha-cypermethrin. Insecticide-impregnated bottles were used as suggested by the CDC/Atlanta. RESULTS: Diagnostic dose for Anopheles darlingi was 12.5ug/bottle during 30 min of exposure. Concentrations for Anopheles marajoara were 20ug/bottle of cypermethrin and deltamethrin and 12.5ug/bottle of alpha-cypermethrin. CONCLUSIONS: No resistance was recorded for Anopheles darlingi , but Anopheles marajoara requires attention. PMID- 26676505 TI - Aedes aegypti eggs oviposited on water surface collected from field ovitraps in Nova Iguacu City, Brazil. AB - INTRODUCTION: Aedes aegypti eggs can be collected from the water surface. METHODS: Aedes aegypti oviposition from 97 field ovitraps was studied. RESULTS: Of the 16,016 eggs collected, 11,439 were obtained from paddles in ovitraps and 4,577 from water. Further, 89 (91.8%) traps contained eggs on water and 22 (22.7%) traps contained eggs only on water. CONCLUSIONS: In field traps, Aedes aegypti females usually oviposit some eggs on water surface suggesting that they might also oviposit on water of some natural breeding, and this possibility needs to be investigated. Eggs oviposited on water need to be considered for collecting trap data. PMID- 26676506 TI - Risk factors for Toxoplasma gondii infection among pregnant women from the State of Tocantins, Northern Brazil. AB - INTRODUCTION: The prevalence of infection by Toxoplasma gondii and associated risk factors in pregnant women in Tocantins, Northern Brazil were assessed. METHODS: Serological analysis was performed in 338 serum samples and an oral questionnaire was utilized to identify potential risk factors. RESULTS: Anti-IgG antibodies against T. gondii were detected in 71% (240/338) of the pregnant women. Prior contact with cats and meat handling were found to be associated with T. gondii infection. CONCLUSIONS: A considerable percentage (29%) of women living in the Tocantins area remain susceptible to infection by the T. gondii protozoon, representing a serious public health risk. PMID- 26676507 TI - Molecular detection of Trypanosoma sp. and Blastocrithidia sp. (Trypanosomatidae) in phlebotomine sand flies (Psychodidae) in the Federal District of Brazil. AB - INTRODUCTION: This study describes the occurrence of trypanosomatids in phlebotomines in Brasilia, Brazil. METHODS: Two hundred and ten females of 13 sand fly species were analyzed by polymerase chain reaction (PCR) using different molecular markers (D7 24Salpha rRNA, kDNA, and ITS1) and sequencing. RESULTS: PCR revealed trypanosomatid-positive samples from Nyssomyia whitmani and Evandromyia evandroi, which were negative by kDNA and ITS1 Leishmania-specific PCRs. DNA sequence analysis of D7 24Salpha rRNA amplicons indicated the occurrence of Blastocrithidia sp. and Trypanosoma sp. in Nyssomyia whitmani and Evandromyia evandroi, respectively. CONCLUSIONS: Two trypanosomatid species other than Leishmania sp. were found to circulate in sand flies in Central Brazil. PMID- 26676509 TI - Severe dengue in the early postoperative period after kidney transplantation: two case reports from Hospital Geral de Fortaleza. AB - Dengue is an arbovirosis that ranges from an asymptomatic presentation to a more severe disease, which is characterized by a vascular leakage syndrome where abdominal pain is a major symptom. Transplant recipients are immunosuppressed and are less likely to develop a severe form of the disease because of a reduction in immune-mediated responses that trigger plasma extravasation events. Herein, we report two cases of severe dengue in the early postoperative period of two kidney transplant recipients. Considering the severity of the cases, we emphasize the importance of dengue screening immediately before transplantation in areas endemic for the disease. PMID- 26676508 TI - First report of schistosomiasis on Serrambi beach, Ipojuca, State of Pernambuco. AB - INTRODUCTION: The expansion of schistosomiasis to previously unaffected areas is being monitored by identifying new cases and georeferencing outbreaks of vector snails. METHODS: In 2014, the Laboratorio de Esquistossomose began an epidemiological survey in Serrambi and registered 2,574 people living there. RESULTS: Of these subjects, 1,414 (54.9%) underwent feces examination and 63 (4.5%) were diagnosed with Schistosoma mansoni infection. At this locality, seven breeding sites each were identified for Biomphalaria straminea and Biomphalaria glabrata. At two sites, B. glabrata were shedding cercariae. CONCLUSIONS: Implementing preventive measures is necessary to avoid the establishment of schistosomiasis in yet another tourist locality, Pernambuco. PMID- 26676510 TI - Dermatitis caused by the tropical fowl mite Ornithonyssus bursa (Berlese) (Acari: Macronyssidae): a case report in humans. AB - We herein report human dermatitis caused by the tropical fowl mite Ornithonyssus bursa (Berlese). The cases occurred in an apartment in a residential district of Porto Alegre City, State of Rio Grande do Sul, Brazil, where three members of the same family presented with pruritic lesions on the arms and legs. On inspecting the bathroom, several mites measuring approximately 1.0mm in length were observed coming from a nest of Rufous Hornero, Furnarius rufus (Gmelin). This is the first report of O. bursa in the urban area of Porto Alegre City, from a nest of F. rufus that bites humans. PMID- 26676511 TI - Concomitant pulmonary and central nervous system paracoccidioidomycosis with cerebellar abscess. PMID- 26676512 TI - Purification of glucose-6-phosphate dehydrogenase and glutathione reductase enzymes from the gill tissue of Lake Van fish and analyzing the effects of some chalcone derivatives on enzyme activities. AB - Glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) are metabolically quite important enzymes. Within this study, these two enzymes were purified for the first time from the gills of Lake Van fish. In the purifying process, ammonium sulfate precipitation and 2',5'-ADP Sepharose 4B affinity column chromatography techniques for glucose-6-phosphate dehydrogenase, temperature degradation and 2',5'-ADP Sepharose 4B affinity column chromatography for glutathione reductase enzyme were used. The control of the enzyme purity and determination of molecular weight were done with sodium dodecyl sulfate polyacrylamide gel electrophoresis. K(M) and V(max) values were determined with Lineweaver-Burk plot. Besides, the effects of some chalcone derivatives on the purified enzymes were analyzed. For the ones showing inhibition effect, % activity-[I] figures were drawn and IC50 values were determined. K(i) value was calculated by using Cheng-Prusoff equation. PMID- 26676513 TI - Mass spectrometry-assisted confirmation of the inability of dipeptidyl peptidase 4 to cleave goldfish peptide YY(1-36) and the lack of anorexigenic effects of peptide YY(3-36) in goldfish (Carassius auratus). AB - Dipeptidyl peptidase-4 (DPP4) is a serine protease of great interest because it has been shown to modulate the activity of several peptidergic factors including peptide YY (PYY) and glucagon-like peptide-1/2. While PYY(1-36) is orexigenic in mammals, PYY(3-36) recently garnered interest as a potent anorexigen. In silico phylogenetic analysis found that the DPP4 cleavage sites are absent in fish PYY sequences. However, no studies were conducted to show that indeed PYY(3-36) is not produced by DPP4 in fish. If DPP4 does not cleave PYY(1-36), is PYY(3-36) an anorexigen in fish? The objectives of this research were to (1) test whether DPP4 cleaves goldfish PYY(1-36) and (2) determine whether PYY(3-36) is an anorexigen in goldfish. First, we identified the highly conserved catalytic region of DPP4 in goldfish. Abundant expression of DPP4 mRNA was found within the gastrointestinal tract. We also report the first MALDI-MS cleavage analysis of DPP4 effects on PYY(1-36) in a non-mammalian vertebrate. Our novel results indicate that DPP4 is unable to cleave goldfish PYY(1-36) to PYY(3-36) in vitro. It also confirms a previously held hypothesis that DPP4 is unable to cleave fish PYY(1-36) that contains N-terminal proline-proline residues. PYY(3-36) had no effects on food intake of goldfish. The appetite inhibitory effects of intraperitoneal and intracerebroventricular injections of 10 ng/g body weight gfPYY(1-36) were abolished by coinjections of BIBP3226, a Y1 receptor antagonist. These results are significant because it shows the lack of generation of endogenous PYY(3-36) and its anorectic effects in goldfish. PMID- 26676514 TI - Survival with nonmelanoma skin cancer in Germany. AB - BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in Germany, but detailed information on survival is lacking. OBJECTIVES: To provide survival estimates for female and male patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site. METHODS: In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis. RESULTS: The absolute and relative 5-year survival were 87.1% and 102.9% for BCC, 77.6% and 93.6% for SCC, 82.1% and 96.0% for sarcoma, 71.4% and 85.7% for adenocarcinoma and 60.0% and 70.7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival. CONCLUSIONS: A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle. PMID- 26676516 TI - Hydroxyapatite nanoparticles formed under a wet mechanochemical method. AB - Hydroxyapatite (HA) nanoparticles were synthesized using a wet mechanochemical method without a calcination process. Dicalcium phosphate dihydrate (CaHPO4 .2H2 O) and calcium carbonate (CaCO3 ) were mixed and milled in a planary mill using ethanol or water as liquid media in the two different synthesized routes. Effects of rotation speed and milling time on the final products formed have been studied. Experimental results showed that HA phase having a characteristic of low crystallinity could be formed under the synthesis route using water. The original phases of both starting chemicals were remained without HA formation in the synthesis route using ethanol. Particle size and morphology of HA nanoparticles were obviously depended on optimum conditions of rotation speed and milling time. Differences on phase formation in both synthesized routes have been considered and discussed based on occurring chemical reaction possibilities. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 679-688, 2017. PMID- 26676515 TI - p53 causes butein-mediated apoptosis of chronic myeloid leukemia cells. AB - Progression of chronic myeloid leukemia, marked by the oncogenic Bcr-Abl mutation, is tightly associated with an alteration of the p53 pathway. It is known that butein extracted from various plants represses cancer growth. Although the anticancer effects of butein are widely accepted, the mechanisms by which butein induces apoptosis of chronic myeloid leukemia cells remains to be elucidated. The present study demonstrated that butein-induced apoptosis was mediated by p53. KBM5 chronic myeloid leukemia (CML) cells expressing wild-type p53 were more sensitive to butein compared with p53-null K562 CML cells in terms of apoptotic cell death. In addition, butein arrested KBM5 cells at S-phase and altered the expression levels of certain cyclins and the p53-downstream targets, MDM2 and p21. In addition, while butein reduced the protein expression of MDM2 in the KBM5 and K562 cells, it resulted in proteasome-independent MDM2 degradation in p53-expressing KBM5 cells, however, not in p53-null K562 cells. Therefore, the present study suggested that p53 causes the butein-mediated apoptosis of leukemic cells. PMID- 26676517 TI - Predicting return to work after subarachnoid hemorrhage using the Montreal Cognitive Assessment (MoCA). AB - BACKGROUND: Returning to work is a major issue for patients having had an aneurysmal subarachnoid hemorrhage (SAH). It is important, at an early stage, to identify the patients that are unlikely to return to work. The objective of this study was to assess the predictive value of the Montreal Cognitive Assessment (MoCA) at 6 months after ictus on return to work at 12 months. METHODS: In this prospective study were 96 patients with SAH included in the acute phase. Cognitive functions were assessed at 6 months using the MoCA and return to work at 12 months. The predictive value of MoCA on return to work was analyzed using the area under the receiver operating characteristic curve as well as logistic regression. RESULTS: Of those that had work before the SAH, 52 % were working at 12 months after the ictus. These patients had scored significantly better on MoCA at 6 months (p = 0.01). The area under the receiver operating characteristic curve was 0.75. By using a cut-off on MoCA of <27, 68 % of the patients could be correctly classified as returned/not returned to work. Adding data from the acute phase to the MoCA in a logistic regression model increased the percentage of patients correctly classified as returned/not returned to work by 2 %. CONCLUSIONS: Returning to work is a major issue for SAH patients. It is important to identify factors that may interfere with a patient's ability to return to work, and address these issues appropriately. In our study, estimating cognitive functions at 6 months after SAH using the MoCA alone allowed us to predict return to work correctly in 68 % of the cases. We feel that this provides useful information in planning rehabilitation, but that other post-SAH symptoms have to be considered as well. PMID- 26676518 TI - [An unusual combination of two rare tumors]. PMID- 26676519 TI - [Muenster Parental Programme--Feedback from Parents: How do parents evaluate an early intervention programme for improving the communication with their baby or toddler with hearing impairment?]. AB - BACKGROUND: With the implementation of the UNHS, early educational services' existing concepts of early intervention have to be adapted to the situation and needs of families with a preverbal child who is deaf or hard of hearing. The Muenster Parental Programme (MPP), a module in early family-centered intervention, fulfils this requirement. OBJECTIVE: We report feedback from participating parents regarding processes and outcomes of the MPP. The self developed questionnaire was checked for its suitability as feedback instrument for measuring parental satisfaction with the MPP. METHOD: 29 parents who participated in the MPP assessed the programme by using the standardised FBB and the self-developed questionnaire FB-MEP, which is specific to the MPP. RESULTS: Using the FBB, 96% of parents judged the MPP to be good or very good. With the FB MEP, parents rated setting, contents and didactics as highly as they did using the FBB (r = 0.7, p < 0.01). In particular, parents judged both the contact and exchange with other affected parents, and the specific individual support for communicating with their child (including video feedback) as especially helpful. CONCLUSIONS: The results reflect parents' high level of satisfaction with the setting, content, didactics and individual benefit gained by their child and themselves from the MPP. The parents are aware of the efficacy of the MPP, which was shown in the controlled intervention study. The self-developed questionnaire FB-MEP was shown to be a suitable instrument for quality assurance measurements of the MPP. PMID- 26676520 TI - [Headache: Otorhinolaryngological aspects]. AB - Headache is the main symptom in a wide variety of diseases of which ear, nose and throat (ENT) entities are only a small fraction but are not reflected in the number of patients. Comprehensive knowledge of the clinical signs of the most common primary headaches, e. g. migraine, is therefore essential for the ENT specialist because the few patients with secondary headache from ENT-related causes must be identified. Reasons for confusing primary headache with e. g. sinusitis are mostly symptoms mediated by the trigeminal nerve, such as nasal obstruction and rhinorrhea because branches of the trigeminal nerve also innervate the meninges. The ENT-specific origin of headaches is characterized by clinical findings of physical organ disease; therefore, from an ENT perspective imaging should be part of the diagnostic procedure as normal imaging findings are indicative of primary headache, which would not normally be treated by an ENT specialist. PMID- 26676521 TI - [Early recognition of cancerous lesions in the mouth and oropharynx: Automated evaluation of hyperspectral image stacks]. AB - BACKGROUND: Early detection of cancerous lesions is still crucial for a patient's prognosis. Although diagnostic access to the oral cavity and oropharynx is comparably easy, the incidence of resulting disease remains high. This is due to the fact that in many cases, malignity is recognized too late on a purely visual basis. Previously, we discussed the application of hyperspectral imaging for early detection of precancerous and cancerous lesions of the larynx. This time, we evaluate the method in the oral cavity and oropharynx. MATERIALS AND METHODS: In 85 patients scheduled for endoscopy, hyperspectral imaging was performed. We used a rigid 0-degree endoscope, a light-adjustable monochromator, and a hyperspectral camera. For evaluation of the method, 3 patients were chosen exemplarily. Training sites from physiological and cancerous tissues were marked. Hyperspectral data from 1 patient were used to train a classifier, which was then used for automatic detection of precancerous and cancerous lesions in another 2 patients. RESULTS: Intraoperative hyperspectral imaging was performed without any problems. Classification showed sensitivities of 61 and 43%, and a specificity of 100%. CONCLUSION: This proof-of-concept study underscores the high potential of hyperspectral imaging for early recognition of cancer in the mouth and oropharynx. Besides a better prognosis for cancer patients, this approach could lead to higher cost efficiency in the health system. PMID- 26676522 TI - Bariatric Surgery for Patients With Type 2 Diabetes--Reply. PMID- 26676523 TI - Sinonasal mucosal melanoma: A 12-year experience of 58 cases. AB - BACKGROUND: Sinonasal mucosal melanoma is a rare malignancy with poor prognosis. METHODS: Patients with sinonasal malignant melanoma who underwent surgery by different approaches were included in this study. Overall survival (OS) and event free survival were calculated, and statistically significant variables by univariate analysis were entered in a multivariate Cox regression model. RESULTS: Pathological staging was pT3, pT4a, and pT4b in 30 cases (51.7%), 17 cases (29.3%), and 11 cases (19.0%). At 3 and 5 years, OS was 43.5% and 29% and event free survival was 23.6% and 12.4%, respectively. At univariate analysis, OS was significantly influenced by male sex, advanced pT classification, positive margins, and surgical approach; event-free survival was affected by positive margins. At multivariate analysis, the risk of death was independently associated with male sex (hazard ratio [HR] = 2.27; p = .04) and positive margins (HR = 2.32; p = .03). CONCLUSION: Male sex and positive margins were negative prognostic factors. Endoscopic resection did not show an increased risk of death compared with more extensive surgical approaches. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1737-E1745, 2016. PMID- 26676524 TI - Towards a consensus on how to diagnose and quantify female pattern hair loss - The 'Female Pattern Hair Loss Severity Index (FPHL-SI)'. AB - BACKGROUND: Female pattern hair loss (FPHL) is a common non-scarring alopecia characterized by widening of the midline hair part at the crown (vertex). In 1977, Ludwig developed a scale that graded the degree of visible vertex hair thinning from I (least severe) to III (most severe). However, by the time patients exhibit the full manifestations of 'Ludwig I', they have already lost a significant volume of hair. Although current therapies may realistically halt progression of hair loss, improvements in hair density is often more limited. Identification and grading of FPHL at an earlier stage is desirable to institute appropriate therapy before significant hair loss has occurred and to enable monitoring over time. AIM: To generate consensus guidance for the recognition and quantification of FPHL that can be used in the clinic. METHODS: Nine clinicians from Europe, North America and Australia experienced in the management of FPHL developed this scale by consensus. RESULTS: We propose a three-point severity scale (termed the FPHL Severity Index (FPHL-SI)) that combines validated measures of hair shedding, midline hair density and scalp trichoscopy criteria to produce a total FPHL-SI score (maximum score = 20). The score is designed to grade FPHL severity over time, while being sufficiently sensitive to identify early disease. A score of 0-4 makes FPHL unlikely; a score of 5-9 would indicate early-stage FPHL, with higher scores indicating greater disease severity. CONCLUSIONS: As a starting point for further public debate, we employ criteria already used in clinical practice to generate a pragmatic FPHL grading system (FPHL-SI) of sufficient sensitivity to identify and monitor early FPHL changes. This may have to be further optimized after systematic validation in clinical practice. PMID- 26676525 TI - Is There a Relationship between Vitamin B12 and Stress Urinary Incontinence? AB - OBJECTIVE: Pelvic floor, which includes collagen, elastin, and smooth muscle, is very important in preventing urinary incontinence (UI). Studies suggest that vitamin B12 is involved in collagen synthesis. In the present study we aimed to determine the association of vitamin B12 deficiency with stress UI in a sample of Turkish women. METHODS: Forty-two women with stress UI or mixed UI who met the inclusion criteria from a group of 541 women with stress UI or mixed UI, were included in the study. The study group was compared with a control group of 20 healthy women without UI who matched to the study group's demographic data and met the inclusion criteria. Demographic data as well as duration of symptoms and vitamin B12 levels were analyzed and compared. RESULTS: The mean ages of the study and the control groups were 50.04 +/- 4.6 and 49.02 +/- 5.1 years, respectively. Vitamin B12 level was 300.95 +/- 142.9 pg/mL in the study group, whereas in the control group it was 598.98 +/- 120.3 pg/mL (P < 0.001). In the study group, 66.6% of the patients with stress UI had vitamin B12 levels less than 300 pg/mL. When the duration of symptoms and vitamin B12 levels were compared, women with vitamin B12 levels less than 200 pg/mL had symptoms for a longer duration (P < 0.01). CONCLUSION: One of the main etiologic factors for stress UI is a defect in pelvic floor support. Vitamin B12 is lower in women with stress UI. Analysis of vitamin B12 levels should also be considered in the evaluation of women with stress UI. PMID- 26676526 TI - Reproduction of Female Lower Urinary Tract Symptoms on Urodynamics. AB - OBJECTIVES: Urodynamic testing (UDS) can be a valuable tool in the assessment of urinary incontinence and voiding dysfunction. The success of UDS in reproducing patients' symptoms has not been well defined. We sought to determine the ability of UDS to reliably reproduce various lower urinary tract symptoms and secondarily the ability of UDS to produce disparate findings not associated with patients presenting symptoms. METHODS: Following Institutional Review Board approval, patient data was accumulated prospectively over 10 months. Notation was made of primary and secondary symptoms as well as if these stated symptoms were reproduced during the urodynamic procedure. Presenting lower urinary tract symptoms included for analysis were stress, mixed and urge incontinence, urgency, and obstructive symptoms. We also reviewed the number of disparate urodynamic observations that did not correlate with patient history. RESULTS: Over a 10 month period, 127 women had interpretable data with respect to whether their presenting symptoms were reproduced during UDS. Presenting symptoms were successfully reproduced on 83% of UDS studies. Disparate urodynamic observations were noted in 60% of patients. CONCLUSIONS: Reproduction of patient symptoms during UDS occurred in the majority of cases if the patient was queried regarding this association. Additional disparate urodynamic observations were also noted in a majority of patients undergoing UDS. It remains unclear whether reproduction of symptoms during UDS in females ultimately results in improved interventional outcomes. The implications of new or unexpected UDS findings during UDS are unknown. PMID- 26676527 TI - Effect of Depression on the Risk and Severity of Lower Urinary Tract Symptoms in Community-Dwelling Elderly Korean Men. AB - OBJECTIVES: To evaluate the association of the risk and severity of lower urinary tract symptoms (LUTS) and depression diagnosed by neuropsychiatrists according to the DSM-IV diagnostic criteria using an objective questionnaire within community dwelling elderly Korean men. METHODS: A total of 392 men who completed urological and psychiatric evaluations as a participant in the Korean Longitudinal Study on Health and Aging were included in this analysis. From each subject, an interview elicited demographic characteristics and medical history, International Prostate Symptom Score was ascertained, and a psychiatric questionnaire was completed. Subjects were analyzed with regard to depression and LUTS severity. RESULTS: The mean age of the subjects was 75 years, 22% were current smokers and 45% were heavy drinkers. Two hundred and twenty-nine subjects (59%) had moderate to severe LUTS and 6.4% of the subjects were diagnosed with major depressive disorders. Those with depression showed higher International Prostate Symptom Score and lower quality of life than the euthymic group (P = 0.03 and P = 0.02, respectively). Severe LUTS was more prevalent in the depression group compared with the euthymic group (P = 0.01). Moderate to severe LUTS was associated with higher age, lower prevalence of hypertension, and higher prevalence of depression than mild LUTS. Univariate and multivariate analyses identified age, hypertension, and depression as significant prognostic factors for moderate to severe LUTS. Depression was the most significant prognostic factor. Depression was associated with 5.81-fold increased odds of having moderate to severe LUTS. CONCLUSION: In older Korean men, depressive symptoms are associated with moderate to severe LUTS. PMID- 26676528 TI - Male Lower Urinary Tract Symptoms: Hypertension as a Risk Factor for Storage Symptoms, but Not Voiding Symptoms. AB - OBJECTIVE: Both the presence of lower urinary tract symptom (LUTS) and that of hypertension (HT) increase with age. We investigated the associations between male LUTS and HT, and also whether alpha1-blockers could allow for the alteration of symptoms. METHODS: The subjects comprised 10 744 men with LUTS in a multicenter Japan-Tamsulosin International Prostate Symptom Score (IPSS) Survey to assess the long-term effects of alpha1-blockers. A total of 4828 men (mean age, 68.5 years) who received a 12-week administration of tamsulosin (0.2 mg/day) were assessed using IPSS and quality of life (QOL) surveys before and after tamsulosin administration. Data were collected by self-administered questionnaires including age, complete history and IPSS at the initial visit. RESULTS: HT was a more common comorbidity (25.9%) than diabetes mellitus (9.9%) or cardiac disease (7.2%). The presence of HT increased significantly with the degree of frequency (mild, 21%; severe, 29%) and nocturia (mild, 23%; severe, 28%), but did not increase with the degree of urgency. Tamsulosin significantly improved all storage and voiding symptoms in every age group above 40 years. The effect of tamsulosin on storage symptoms was more prominent in patients with HT than in patients without it. Concerning voiding symptoms, however, tamsulosin was as effective in patients with HT as it was in patients without HT. CONCLUSION: HT represents a risk factor for the increased frequency and severity of storage symptoms and it also influences the efficacy of alpha1-blockers. PMID- 26676529 TI - Defining Causes for Overactive Bladder Symptoms in Women. AB - OBJECTIVES: The aim of the present study was to determine the causes for overactive bladder (OAB) symptoms in women visiting a urological clinic. METHODS: We prospectively recruited female patients with OAB symptoms between December 2008 and February 2010. All patients were interviewed for their detailed personal and medical history. All patients completed a 3-day frequency-volume chart. Symptom severity was evaluated using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) questionnaires. All patients underwent either conventional pressure-flow urodynamic studies or video urodynamic studies. On the basis of these evaluations, patients were assigned to one of the following categories: idiopathic OAB, stress urinary incontinence (SUI)-associated, neurogenic bladder, or bladder outlet obstruction (BOO). RESULTS: A total of 108 female patients were recruited into the study. The mean age of the patients was 63.75 +/- 14.02 years (range: 23-89). Detrusor overactivity was demonstrated in 55 patients (51%). The differential diagnosis was idiopathic OAB in 51 women (47.2%), SUI-associated in 46 (42.6%), neurogenic bladder in 13 (12.0%) and BOO in 7 (6.5%). CONCLUSION: Our study suggests that the causes for OAB symptoms could be defined in half of the women visiting a urological clinic. Among them, SUI was the most common. Moreover, OAB symptoms in women might relate to BOO. Detailed history taking and sophisticated urodynamic studies are required for a substantial group of female patients with OAB symptoms to make the correct diagnosis and provide optimal therapy. PMID- 26676530 TI - Furosemide versus Gosha-Jinki-Gan, a Blended Herbal Medicine, for Nocturnal Polyuria: A Randomized Crossover Trial. AB - OBJECTIVES: To investigate the efficacy of two types of drugs, furosemide and gosha-jinki-gan (GJG), for treatment of nocturia with nocturnal polyuria using a randomized crossover method. METHODS: A total of 36 patients with nocturnal polyuria were recruited for this study. We assessed the International Prostate Symptom Score (I-PSS), Pittsburgh Sleep Quality Index (PSQI), frequency volume charts, blood pressure, urine chemistry, serum B-type natriuretic peptide (BNP) and body fluid compartments. RESULTS: Both furosemide and GJG significantly improved the nocturia score in the I-PSS, the I-PSS Quality of Life (QOL) score, actual nocturnal frequency and hours of undisturbed sleep compared with those at baseline. Nocturnal frequency and nocturnal urine volume were more significantly reduced by furosemide treatment than with GJG treatment. The I-PSS total score and nocturnal urine volume significantly improved only by furosemide treatment. CONCLUSION: Furosemide treatment definitively improved nocturia with nocturnal polyuria. GJG treatment may also induce mild improvement of nocturnal polyuria, although further study is required to confirm its efficacy. PMID- 26676531 TI - Changes in Urodynamics and Lower Urinary Tract Symptoms after Radical Prostatectomy: Implications of Preoperative Detrusor Contractility. AB - OBJECTIVES: Our goal was to identify changes in urodynamic parameters and lower urinary tract symptoms (LUTS) in men followed for1 year after radical prostatectomy (RP) compared to the preoperative measures with a specific focus on detrusor contractility. METHODS: This study enrolled 43 patients who received RP (laparoscopic 27, retropubic: 16) and pressure flow studies (PFS) pre-RP as well as 12 months (M) after RP. No patients complained of urinary incontinence preoperatively. Urodynamic studies and questionnaires regarding LUTS and urinary continence were conducted before and 12 M after RP. Detrusor underactivity (DU) was defined as <10 (W/m(2) ) in preoperative maximum watts factor value. RESULTS: Urodynamics demonstrated that RP improved urodynamic parameters by releasing bladder outlet obstruction without affecting overall detrusor contractility. Meanwhile, RP did not affect bladder capacity, bladder compliance, or detrusor contractility. LUTS in the International Prostate Symptom Score (IPSS), including the IPSS subscore, was not improved. The quality of life score was significantly better at 12 M after RP and continence rates were gradually improved to be at a satisfactory level in more than 80% of patients by 12 M after RP. DU was preoperatively identified in 21(49%) patients, influencing urodynamic parameters and LUTS preoperatively. However, DU did not affect urodynamic parameters and LUTS after RP. CONCLUSION: Although RP improves urodynamic parameters, it does not significantly affect LUTS. Urinary continence gradually improves and is satisfactory within 1 year after RP. The status of preoperative detrusor contractility did not affect urodynamic parameters or LUTS after RP. PMID- 26676532 TI - Is Major Depression a Risk for Bladder, Bowel, and Sexual Dysfunction? AB - OBJECTIVES: Although major depression may accompany bladder, bowel and sexual (pelvic organs) dysfunction, no prospective, controlled surveys have been available. The aim of the present study was to study the risk of pelvic organ dysfunction in major depression. METHODS: Two hundred and twenty-four depression patients in the psychiatry clinic (97 men, 127 women; average age 42 years; 128 drug-naIve, 96 medicated) and 391 age-matched local individuals who were undergoing an annual health survey underwent a questionnaire devised for neurologic and psychiatric cohorts. RESULTS: Compared with control, in the drug naIve group the frequency of dysfunction was significantly higher for urinary urgency (20.9% of the women, 25.9% of the men, P < 0.01), urinary incontinence (9.1%, women), retardation in initiating urination (13.1%, men); constipation (23.8%, 14.8%), diarrhea (20.3%, 21.8%); decrease in libido (42%, men), sexual intercourse (70.7%, 78.7%) orgasm (63.6%, 65.0%), erection (92.7% of the men); and quality of life indices. No difference was found in the frequency of all three items between the drug-naIve group and the medicated group. CONCLUSION: The results of the present study suggest that major depression is a risk for all bladder, bowel and sexual dysfunction, and it significantly worsens quality of life in patients. This finding presumably reflects that pelvic organ function is under emotional control. Amelioration of bladder, bowel, and sexual dysfunction is therefore an important target to treat patients with major depression. PMID- 26676533 TI - Efficacy of Dose Escalation of Tamsulosin for the Treatment of Lower Urinary Tract Symptoms. AB - OBJECTIVES: The aim of this study was to compare the efficacy of low (0.2 mg) and intermediate (0.4 mg) dose tamsulosin in treating lower urinary tract symptoms (LUTS). METHODS: Patients were treated with low-dose tamsulosin for an initial run-in period of 12 weeks, then divided into two groups based on their clinical improvement. Patients were measured for objective parameters of peak flow rate and postvoid residual urine volume, as well as subjective symptom scores and perceived patient benefit of treatment. The items were then integrated as the LUTS Outcome Score to determine dose increase or maintenance. Overall outcome was determined at 36 weeks. RESULTS: One hundred and seventy-four patients were enrolled and started on 0.2 mg tamsulosin treatment. One hundred and fifty-five patients completed the 36-week study. Sixty patients required dose increase to 0.4 mg at the 12th week. Baseline characteristics showed that a patient who would benefit from 0.4 mg dosage had higher age, daytime frequency, and lower peak urine flow rate. Patients receiving both 0.2 and 0.04 mg both showed improved clinical outcome measures. Higher improvement was found in voiding component symptom scores and urine flow rate improvement in patients receiving an increased dose. CONCLUSION: Both low- and intermediate-dose tamsulosin are effective treatment regimens. Increasing from low to intermediate dose should follow assessment of both objective and subjective improvements. PMID- 26676534 TI - Normalized Dysfunctional Voiding Through Timed Voiding. AB - We report a 3-year-old girl with dysfunctional voiding, febrile urinary tract infection (UTI) and bladder over distention (BOD). After controlling UTI, repeat uroflowmetry depicted staccato flow pattern and postvoid residual (PVR) urine volume was >20 mL. Frequency/volume chart showed voided volume was frequently larger than >100% expected bladder capacity. BOD resulted in dysfunctional voiding and elevated PVR was impressed. Urotherapy with adequate fluids intake, and timed voiding to avoid BOD were taught. Subsequent frequency/volume chart disclosed that voided volume was not greater than 100% expected bladder capacity. Uroflowmetry curves were normalized and PVR decreased. Without prophylactic antibiotics, she was free of UTI for 12 months. Unfortunately, she held urine after attending kindergarten and got febrile UTI again. BOD was impressed and timed voiding was re-initiated after resolution of UTI. She was free of UTI and antibiotics for another 15 months. Bladder over distension may be the cause of dysfunctional voiding, vesicoureteral reflux and UTI. Through timed voiding, BOD may be reversed and UTI may be prevented. PMID- 26676535 TI - Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess. AB - Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive-aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels. PMID- 26676536 TI - Detection and quantitation of chromosomal mosaicism in human blastocysts using copy number variation sequencing. AB - OBJECTIVE: Currently, our understanding of the nature and reproductive potential of blastocysts associated with trophectoderm (TE) lineage chromosomal mosaicism is limited. The objective of this study was to first validate copy number variation sequencing (CNV-Seq) for measuring the level of mosaicism and second, examine the nature and level of mosaicism in TE biopsies of patient's blastocysts. METHOD: TE biopy samples were analysed by array comparative genomic hybridization (CGH) and CNV-Seq to discriminate between euploid, aneuploid and mosaic blastocysts. RESULTS: Using artificial models of TE mosaicism for five different chromosomes, CNV-Seq accurately and reproducibly quantitated mosaicism at levels of 50% and 20%. In a comparative 24-chromosome study of 49 blastocysts by array CGH and CNV-Seq, 43 blastocysts (87.8%) had a concordant diagnosis and 6 blastocysts (12.2%) were discordant. The discordance was attributed to low to medium levels of chromosomal mosaicism (30-70%) not detected by array CGH. In an expanded study of 399 blastocysts using CNV-Seq as the sole diagnostic method, the proportion of diploid-aneuploid mosaics (34, 8.5%) was significantly higher than aneuploid mosaics (18, 4.5%) (p < 0.02). CONCLUSION: Mosaicism is a significant chromosomal abnormality associated with the TE lineage of human blastocysts that can be reliably and accurately detected by CNV-Seq. PMID- 26676537 TI - Molecular Polyarsenides of the Rare-Earth Elements. AB - Reduction of [Cp*Fe(eta(5)-As5)] with [Cp''2Sm(thf)] (Cp''=eta(5)-1,3-(tBu)2C5H3) under various conditions led to [(Cp''2Sm)(MU,eta(4):eta(4)-As4)(Cp*Fe)] and [(Cp''2Sm)2As7(Cp*Fe)]. Both compounds are the first polyarsenides of the rare earth metals. [(Cp''2Sm)(MU,eta(4):eta(4)-As4)(Cp*Fe)] is also the first d/f triple decker sandwich complex with a purely inorganic planar middle deck. The central As4(2-) unit is isolobal with the 6pi-aromatic cyclobutadiene dianion (CH)4(2-). [(Cp''2Sm)2As7(Cp*Fe)] contains an As7(3-) cage, which has a norbornadiene-like structure with two short As-As bonds in the scaffold. DFT calculations confirm all the structural observations. The As-As bond order inside the cyclo As4 ligand in [(Cp''2Sm)(MU,eta(4):eta(4)-As4)(Cp*Fe)] was estimated to be in between an As-As single bond and a formally aromatic As4(2-) system. PMID- 26676538 TI - Oxidative stress and renal toxicity after subacute exposure to decabrominated diphenyl ether in Wistar rats. AB - Fully brominated diphenyl ether (BDE-209) is a flame retardant widely used in plastics and textiles. Because of its high persistence, humans are exposed to it continuously, mainly via dust ingestion. We investigated effects of BDE-209 on renal function and oxidative stress development in the kidney after subacute exposure in rats. Five groups of animals were given by oral gavage 31.25-500 mg BDE-209/kg b.w./day for 28 days, and relative kidney weight, serum urea and creatinine, and oxidative stress parameters in the kidney were determined. Benchmark-dose approach was used for dose response modeling. Serum creatinine was increased, while results obtained for serum urea were inconclusive. Relative kidney weight was not affected by BDE-209. Kidney reduced glutathione was elevated, while superoxide dismutase activity was not changed after BDE-209 treatment. Also, levels of thiobarbituric acid reactive substances (TBARS) were increased and total -SH groups were decreased, which indicated oxidative imbalance. The critical effect dose (CED)/CEDL ratios for the effects on TBARS and total -SH groups indicated estimated CEDs for these markers can be used in risk assessment of BDE-209. Our study results have shown that a relatively low dose of BDE-209 affects kidney function and that oxidative stress is one of the mechanisms of its nephrotoxicity. PMID- 26676539 TI - Photodegradation applied to the treatment of phenol and derived substances catalyzed by TiO2/BiPO4 and biological toxicity analysis. AB - For this work, a phenol solution model was treated by an advanced oxidation process (AOPs), using the heterogeneous catalyst TiO2/BiPO4 and hydrogen peroxide combined with UVA for 240 min. An annular reactor containing a UVA lamp (80 W) was employed. A central composite rotacional design was developed employing a TiO2/BiPO4 concentration of 87 mg L-1 and a hydrogen peroxide concentration of 1800 mg L-1, being evaluated by the degradation percentage and phenol mineralization percentage as responses; 94.30 and 67.00 % were obtained for the phenol degradation and total organic carbon (TOC) conversion, respectively. The lumped kinetic model (LKM) was applied and a satisfactory profile of the residual fractions of the organic compounds present in the liquid phase as a time function with a determination coefficient (R 2 = 0.9945). The toxicity tests employing microbiological species indicated that the organisms tested for the evaluation of the toxic compounds present in the contaminated samples presented a practical low cost test, rapid execution, and high sensibility as an indicator of the presence of toxic substances in liquid effluents. PMID- 26676540 TI - Transport of organic contaminants in subsoil horizons and effects of dissolved organic matter related to organic waste recycling practices. AB - Compost amendment on agricultural soil is a current practice to compensate the loss of organic matter. As a consequence, dissolved organic carbon concentration in soil leachates can be increased and potentially modify the transport of other solutes. This study aims to characterize the processes controlling the mobility of dissolved organic matter (DOM) in deep soil layers and their potential impacts on the leaching of organic contaminants (pesticides and pharmaceutical compounds) potentially present in cultivated soils receiving organic waste composts. We sampled undisturbed soil cores in the illuviated horizon (60-90 cm depth) of an Albeluvisol. Percolation experiments were made in presence and absence of DOM with two different pesticides, isoproturon and epoxiconazole, and two pharmaceutical compounds, ibuprofen and sulfamethoxazole. Two types of DOM were extracted from two different soil surface horizons: one sampled in a plot receiving a co-compost of green wastes and sewage sludge applied once every 2 years since 1998 and one sampled in an unamended plot. Results show that DOM behaved as a highly reactive solute, which was continuously generated within the soil columns during flow and increased after flow interruption. DOM significantly increased the mobility of bromide and all pollutants, but the effects differed according the hydrophobic and the ionic character of the molecules. However, no clear effects of the origin of DOM on the mobility of the different contaminants were observed. PMID- 26676541 TI - Diurnal variability and biogeochemical reactivity of mercury species in an extreme high-altitude lake ecosystem of the Bolivian Altiplano. AB - Methylation and demethylation represent major transformation pathways regulating the net production of methylmercury (MMHg). Very few studies have documented Hg reactivity and transformation in extreme high-altitude lake ecosystems. Mercury (Hg) species concentrations (IHg, MMHg, Hg degrees , and DMHg) and in situ Hg methylation (M) and MMHg demethylation (D) potentials were determined in water, sediment, floating organic aggregates, and periphyton compartments of a shallow productive Lake of the Bolivian Altiplano (Uru Uru Lake, 3686 m). Samples were collected during late dry season (October 2010) and late wet season (May 2011) at a north (NS) and a south (SS) site of the lake, respectively. Mercury species concentrations exhibited significant diurnal variability as influenced by the strong diurnal biogeochemical gradients. Particularly high methylated mercury concentrations (0.2 to 4.5 ng L(-1) for MMHgT) were determined in the water column evidencing important Hg methylation in this ecosystem. Methylation and D potentials range were, respectively, <0.1-16.5 and <0.2-68.3 % day(-1) and were highly variable among compartments of the lake, but always higher during the dry season. Net Hg M indicates that the influence of urban and mining effluent (NS) promotes MMHg production in both water (up to 0.45 ng MMHg L(-1) day(-1)) and sediment compartments (2.0 to 19.7 ng MMHg g(-1) day(-1)). While the sediment compartment appears to represent a major source of MMHg in this shallow ecosystem, floating organic aggregates (dry season, SS) and Totora's periphyton (wet season, NS) were found to act as a significant source (5.8 ng MMHg g(-1) day(-1)) and a sink (-2.1 ng MMHg g(-1) day(-1)) of MMHg, respectively. This work demonstrates that high-altitude productive lake ecosystems can promote MMHg formation in various compartments supporting recent observations of high Hg contents in fish and water birds. PMID- 26676542 TI - Identification of a novel hydroxylated metabolite of 2,2',3,5',6 pentachlorobiphenyl formed in whole poplar plants. AB - Polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants consisting of 209 congeners. Oxidation of several PCB congeners to hydroxylated PCBs (OH-PCBs) in whole poplar plants has been reported before. Moreover, 2,2',3,5',6-pentachlorobiphenyl (PCB95), as a chiral congener, has been previously shown to be atropselectively taken up and transformed in whole poplar plants. The objective of this study was to determine if PCB95 is atropselectively metabolized to OH-PCBs in whole poplar plants. Two hydroxylated PCB95s were detected by high-performance liquid chromatography-mass spectrometry in the roots of whole poplar plants exposed to racemic PCB95 for 30 days. The major metabolite was confirmed to be 4'-hydroxy-2,2',3,5',6-pentachlorobiphenyl (4'-OH-PCB95) by gas chromatography-mass spectrometry (GC-MS) using an authentic reference standard. Enantioselective analysis showed that 4'-OH-PCB95 was formed atropselectively, with the atropisomer eluting second on the Nucleodex beta-PM column (E2-4'-OH-PCB95) being slightly more abundant in the roots of whole poplar plants. Therefore, PCB95 can at least be metabolized into 4'-OH-PCB95 and another unknown hydroxylated PCB95 (as a minor metabolite) in whole poplar plants. Both atropisomers of 4'-OH-PCB95 are formed, but E2-4'-OH-PCB95 has greater atropisomeric enrichment in the roots of whole poplar plants. A comparison with mammalian biotransformation studies indicates a distinctively different metabolite profile of OH-PCB95 metabolites in whole poplar plants. Our observations suggest that biotransformation of chiral PCBs to OH-PCBs by plants may represent an important source of enantiomerically enriched OH-PCBs in the environment. PMID- 26676543 TI - Variability in the levels of 3-phenoxybenzoic acid by age, gender, and race/ethnicity for the period of 2001-2002 versus 2009-2010 and its association with thyroid function among general US population. AB - Data from National Health and Nutrition Examination Survey for the years 2007 2008 were used to evaluate the impact of the observed levels of 3-phenoxybenzoic acid (3-PBA) in urine on the levels of thyroid hormones in serum for those aged >=12 years. There was no evidence of any association between the levels of 3-PBA and thyroid function. As compared to their levels in 2001-2002, levels of 3-PBA rose (p <= 0.03) in 2009-2010 for children, adolescents, adults aged 20-64 years, males, females, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, non smokers, and smokers. Rise in the levels of 3-PBA among children aged 6-11 years was higher than the similar rise in all other demographic groups. Since the levels of 3-PBA are still on the rise, previously observed adverse health effects among children associated with the levels of 3-PBA require that additional preventive measures be put in place to protect them from exposure to pyrethroids. PMID- 26676544 TI - Mine land valorization through energy maize production enhanced by the application of plant growth-promoting rhizobacteria and arbuscular mycorrhizal fungi. AB - The use of heavy metals (HM) contaminated soils to grow energy crops can diminish the negative impact of HM in the environment improving land restoration. The effect of two PGPR (B1--Chryseobacterium humi ECP37(T) and B2--Pseudomonas reactans EDP28) and an AMF (F--Rhizophagus irregularis) on growth, Cd and Zn accumulation, and nutritional status of energy maize plants grown in a soil collected from an area adjacent to a Portuguese mine was assessed in a greenhouse experiment. Both bacterial strains, especially when co-inoculated with the AMF, acted as plant growth-promoting inoculants, increasing root and shoot biomass as well as shoot elongation. Cadmium was not detected in the maize tissues and a decrease in Zn accumulation was observed for all microbial treatments in aboveground and belowground tissues--with inoculation of maize with AMF and strain B2 leading to maximum reductions in Zn shoot and root accumulation of up to 48 and 43%, respectively. Although microbial single inoculation generally did not increase N and P levels in maize plants, co-inoculation of the PGPR and the AMF improved substantially P accumulation in roots. The DGGE analysis of the bacterial rhizosphere community showed that the samples inoculated with the AMF clustered apart of those without the AMF and the Shannon-Wiener Index (H') increased over the course of the experiment when both inoculants were present. This work shows the benefits of combined inoculation of AMF and PGPR for the growth energy maize in metal contaminated soils and their potential for the application in phytomanagement strategies. PMID- 26676545 TI - The effect of microbial sulfidogenesis on the stability of As-Fe coprecipitate with low Fe/As molar ratio under anaerobic conditions. AB - The effect of microbial sulfidogenesis on As transformation and mobilization in solid phase with low Fe/As ratio is still not well known. In this study, microbial transformation and mobilization of As in the As-Fe coprecipitate with different sulfate levels were investigated using chemical extraction and K-edge XANES of As and S. Results showed that approximately 2.7, 24.4, and 83.7 % of total As were released into the aqueous phase in the low-, mid-, and high-sulfate treatments, respectively, indicating that the presence of large amounts of sulfate could enhance microbial arsenic mobilization in the As-Fe coprecipitate. In the low-sulfate treatment, As mobilization was primarily attributed to the reductive dissolution of the Fe (oxy)hydroxides and the As reduction and desorption. In the mid- and high-sulfate treatments, the reduction of arsenate and ferric iron was significantly enhanced. Complete ferric iron reduction was observed in the solid phase, implying that Fe (oxy)hydroxide was transformed to secondary minerals and may be the one of the primary causes for the enhanced As mobilization. Thermodynamic calculations predicted the formation of thioarsenite species after 35 days of incubation based on the concentration of dissolved As(III) and S(-II). Since thioarsenic species is more mobile, its formation may be one of the most important factors enhancing the As release in the high-sulfate system. The result of this study is of significance to completely predict the environmental behavior of As associated with Fe (hydr)oxides in the presence of microbial sulfidogenesis under anoxic conditions. PMID- 26676546 TI - Semi-continuous sampling of health relevant atmospheric particle subfractions for chemical speciation using a rotating drum impactor in series with sequential filter sampler. AB - To achieve unattended continuous long-term (eg., 1 week) sampling of size segregated 24-h ambient particulate matter (PM), a sampling strategy of a modified 3-stage rotating drum impactor (RDI) in series with a sequential filter sampler was introduced and verified in a field campaign. Before the field sampling, lab experiment was conducted to test the collection efficiency of the third stage of the RDI using the quartz-fiber filter (QFF) as the substrate. The measured value is 0.36 MUm, which is larger than the nominal value 0.1 MUm. A fast direct analysis of organic species in all size fractions (<0.36, 0.36-1, 1 2.4, and 2.4-10 MUm) of 24-h ambient samples was done using in situ derivatization thermal desorption gas chromatography time-of-flight mass spectrometry (IDTD-GC-TOFMS). A few secondary originated polar markers (dicarboxylic acids, cis-pinonic acid, etc.) were introduced and evaluated using this method for the first time and quantified simultaneously with polycyclic aromatic hydrocarbons (PAH) in the filter samples (<0.36 MUm). For the other RDI strip samples (0.36-1, 1-2.4, and 2.4-10 MUm), PAH and levoglucosan were quantified. The comparability of two such sampler sets was verified with respect to the PM collection profile of the two RDIs as well as measured concentration of chemical compounds in each sampled size fraction, so that a future epidemiological study on the relationship between the finest PM/its chemical composition and health outcome could be carried out through parallel sampling at two sites. The internal correlations between the size-segregated organic compounds are discussed. Besides, the correlations between the size-segregated organic species and size-segregated particulate number concentration (PNC) as well as meteorological parameter are discussed as well. PMID- 26676547 TI - Hybrid electrooxidation and adsorption process for the removal of ammonia in low concentration chloride wastewater. AB - The ammonia removal performance of a hybrid electrooxidation and adsorption reactor (HEAR) is evaluated. The influences of current density, chloride concentration, and packing particles for ammonia removal in HEAR were investigated, and the performance of HEAR under serials circulation was studied. Results indicated that ammonia removal efficiency achieved around 70 % under the optimal condition after 30-min electrolysis. The optimal condition was determined as current density of 10 mA/cm2, Cl-/NH4+ molar ratio of 1.8, and modified zeolites as particles. The ammonia adsorption kinetic and adsorption isotherm on zeolites fitted well with second-order kinetic and Langmuir isotherm model, respectively. Adsorption amount of ammonia on zeolites sampled at 30-min electrolysis achieved 2.4 mg/L, higher than 1.9 mg/L of zeolites at 20-min electrolysis, indicating that electrooxidation coupled with adsorption led to simultaneous ammonia removal and zeolite regeneration in HEAR. No decrease of ammonia removal efficiency was observed over several cycles with the electrooxidation treatment. The presence of free chlorine indicating ammonia removal in HEAR was due to the combined influence by adsorption and indirect electrooxidation. These results showed that HEAR was a prospective alternative as a tertiary treatment for wastewater with low chloride ions. PMID- 26676548 TI - Epigenetic regulation of proliferation and invasion in hepatocellular carcinoma cells by CBP/p300 histone acetyltransferase activity. AB - Altered epigenetic control of gene expression plays a substantial role in tumor development and progression. Accumulating studies suggest that somatic mutations of CREB binding proteins (CBP)/p300 occur in some cancer cells. CBP/p300 possess histone acetyltransferase (HAT) activity, and are involved in many cellular processes. In this study, we investigated the expression and functional role of CBP/p300 in hepatocellular carcinoma (HCC) using the specific inhibitor C646 of CBP/p300 HAT activity. We examined its effect on several apoptosis-related proteins and invasion-related genes. The results showed that CBP/p300 were highly expressed in HCC tissues and that expression of p300, but not of CBP, was strongly correlated with the malignant character of HCC. C646 inhibited proliferation of HCC cell lines in a dose dependent manner. C646 significantly augmented TRAIL-induced apoptotic sensitivity, which was accompanied by reduced levels of survivin, in HepG2, HLE and SK-HEP1 cells. C646 significantly inhibited invasion of Huh7, HLE and SK-HEP1 cells. The level of matrix metallopeptidase 15 (MMP15) mRNA expression was significantly reduced, whereas the level of laminin alpha 3 (LAMA3) and secreted phosphoprotein 1 (SPP1) mRNA expression was significantly increased in Huh7 cells following exposure to C646. In conclusion, our results suggest that CBP/p300 HAT activity has an important role in malignant transformation, proliferation, apoptotic sensitivity and invasion in HCC. CBP/p300 could be a promising therapeutic target in HCC. PMID- 26676549 TI - Ultra-small Nd(3+)-doped nanoparticles as near-infrared luminescent biolabels of hemin in bacteria. AB - Near-infrared (NIR) luminescent Nd(3+)-doped nanoparticles (NPs) have attracted considerable attention in bioimaging and biodetection. Here, we demonstrate sub-6 nm NaGdF4:Nd(3+),Fe(3+) NPs as luminescent biolabels of hemin molecules that act as the exogenous electron carriers in microbial communities. Contrary to the severe quenching of the visible luminescence for either upconverting or downconverting NPs, the Nd(3+)-doped NPs show superior properties in avoiding the optical absorption of hemin within the UV and visible spectral regions. A detailed examination showed that the Nd(3+)-doped NPs exhibit no obvious toxic effects on the microbial communities and show scarce influence on the characteristics of labeled hemin molecules in enhancing the reducing power of the fermentation system. More importantly, by monitoring the NIR luminescence of Nd(3+)-doped NPs, the selective accumulation of exogenous electron carriers in bacteria that are lacking reducing power has been revealed for the first time. The application of Nd(3+)-doped NPs as biolabels in bacteria would provide new opportunities for further unravelling the role of exogenous electron carriers in anaerobic digestion. PMID- 26676550 TI - Authors' correction for Euro Surveill. 2015;20(47). PMID- 26676551 TI - Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo. AB - The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose dependent manner; ii) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); iii) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; iv) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future. PMID- 26676552 TI - Detection of nerve gases using surface-enhanced Raman scattering substrates with high droplet adhesion. AB - Threats from chemical warfare agents, commonly known as nerve gases, constitute a serious security issue of increasing global concern because of surging terrorist activity worldwide. However, nerve gases are difficult to detect using current analytical tools and outside dedicated laboratories. Here we demonstrate that surface-enhanced Raman scattering (SERS) can be used for sensitive detection of femtomol quantities of two nerve gases, VX and Tabun, using a handheld Raman device and SERS substrates consisting of flexible gold-covered Si nanopillars. The substrate surface exhibits high droplet adhesion and nanopillar clustering due to elasto-capillary forces, resulting in enrichment of target molecules in plasmonic hot-spots with high Raman enhancement. The results may pave the way for strategic life-saving SERS detection of chemical warfare agents in the field. PMID- 26676554 TI - [Aesthetic Surgery in Children and Adolescents]. PMID- 26676553 TI - Microbiology and resistance in first episodes of spontaneous bacterial peritonitis: implications for management and prognosis. AB - PURPOSE: International guidelines for antibiotic treatment of spontaneous bacterial peritonitis (SBP) are based on studies conducted decades ago and do not reflect regional differences of bacterial epidemiology. METHODS: We retrospectively analyzed epidemiology of agents, antibiotic resistance patterns, and survival in liver cirrhosis patients with their first episode of SBP during the years 2007-2013. RESULTS: Of the 311 patients included, 114 patients had a positive ascites culture, and 197 had an ascitic neutrophil count >250 MUL. Gram positive bacteria (47.8%) were more frequently found than Gram-negatives (44.9%), fungi in 7.2%. Enterobacter spp. (40.6%), Enterococcus spp. (26.1%), and Staphylcoccus spp. (13.8%) were the most frequently isolated agents. Third generation cephalosporins covered 70.2% of non-nosocomial and 56.3% of nosocomial acquired SBP cases.When SBP was diagnosed by a positive ascitic culture, survival was highly significantly reduced (mean: 13.9 +/- 2.9 months; 95% confidence interval [CI]: 8.1-19.8) compared with culture-negative SBP patients (mean: 44.1 +/- 5.4 months; 95% CI: 33.4-54.9; P = 0.000). Along with model of end-stage liver disease score and intensive care unit contact, a positive ascites culture remained an independent risk factor associated with poor survival (odds ratio: 1.49; 95% CI: 1.09-2.03) in multivariate analysis; piperacillin/tazobactam proved to be an adequate antibiotic for nosocomial and non-nosocomial SBP in 85.1% and 92.5%, respectively. SBP infection with Enterococcus spp. was associated with poor patient survival (P = 0.048). CONCLUSIONS: Third-generation cephalosporins have poor microbial coverage for treatment of SBP. Current guidelines need to adapt for the emerging number of Gram-positive infectious agents in SBP patients. PMID- 26676555 TI - [Reconstruction of Defects after Oncologic Resection and Radiation - Indications for Microsurgical Reconstruction]. AB - The surgical treatment of soft tissue sarcomas in the extremities frequently requires radiation therapy to achieve local tumour control. However, both adjuvant and neoadjuvant radiation are associated with significant morbidity caused by impaired wound healing, ulcers or osteonecrosis with subsequent fractures. This is due to altered local cell mediator levels, fibrosis occurring simultaneously with decreased cell division rates and diminished vascularity. This article describes a number of local conservative treatment options, all of which have limited success rates. In addition, it describes plastic surgical treatment options for radiation-induced local morbidity. Surgical reconstruction includes the full range of plastic reconstructive techniques. However, less complex options such as random pattern flaps or split thickness skin grafts are often associated with complications. Therefore, a large number of cases require free tissue transfer. PMID- 26676556 TI - [Latissimus Dorsi Monitoring Island Perforator Propeller Flap as a Lifeboat in Consecutive Defect Coverage: Technical Innovation and Review of the Literature]. PMID- 26676557 TI - [Establishment and Evaluation of a Microsurgery Course for Medical Students]. AB - BACKGROUND: Very few microsurgical courses have been offered for medical students in Germany to date. To raise early interest in this technique, which is essential for plastic and reconstructive surgery, and to guide eligible medical students to choose plastic surgery as their specialist field, the Department of Plastic and Hand Surgery, supported by the Faculty of Medicine of the Friedrich-Alexander University of Erlangen-Nuremberg, implemented a microsurgical course for students in 2011. This study describes the implementation of that course and evaluates its impact on the subsequent choice of the participants' specialist fields. MATERIAL AND METHODS: Since the summer of 2011, the microsurgery course for medical students has taken place regularly 3 times per term. It is free of charge for participants and is guided by senior physicians of the Department of Plastic and Hand Surgery together with student tutors from the Faculty of Medicine. The arterial end-to-end anastomosis in the fresh chicken leg is used as a training model. Based on a questionnaire survey the participants were evaluated and statistically analysed regarding their course satisfaction, self-assessment of their own eligibility before and after the course, the anticipated future choice of their medical specialist field and how their choice was influenced by this course. RESULTS: After the successful implementation of the microsurgical course in 2011, a significant number of students were interested in microsurgery. According to the questionnaire, the level of enthusiasm was high among all participants. The self-assessment of microsurgical skills improved significantly after the course compared with the pre-course assessment. In 82% of the participants, the course had a strong positive influence on the future choice of their specialist field. CONCLUSIONS: The regular implementation of a microsurgical course for students in the form described here is practicable and possible without undue personnel and cost of materials. The ongoing interest among students in such an offer is enormous and the satisfaction of the participants is very high. This might be a way to recruit future plastic surgeons by raising early enthusiasm for microsurgery. These future plastic surgeons, in turn, would be given the chance to experience a very fascinating aspect of plastic surgery, which might help them to decide on their specialisation within that field at a later point in their career. PMID- 26676558 TI - [HaMiPla Best Paper Award - Your Favourites in 2014]. PMID- 26676559 TI - [Personal Congratulations on occasion of the 75th Birthday of Ulrich Lanz]. PMID- 26676561 TI - Effect of microbubble-enhanced ultrasound on percutaneous ethanol ablation of rat walker-256 tumour. AB - OBJECTIVES: Percutaneous ethanol ablation (PEA) is an effective method for treating small liver cancer. Microbubble-enhanced ultrasound (MEUS) can potentially promote PEA by disrupting the tumour's circulation. In this study, treatment combining MEUS and PEA was performed to find any synergistic effects in tumour ablation. METHODS: Ten rats bearing subcutaneous Walker-256 tumours were treated by MEUS combined with PEA. The other 18 tumour-bearing rats that were treated by MEUS or PEA served as the controls. MEUS was conducted by therapeutic ultrasound (TUS) and microbubble injection. TUS was operated at a frequency of 831 KHz with a pressure amplitude of 4.3 MPa. Tumour blood perfusion was assessed by contrast-enhanced ultrasound (CEUS), and the tumour necrosis rate was determined by histological examination. RESULTS: CEUS showed that the tumour blood perfusion almost vanished in all of the MEUS-treated tumours. The contrast peak intensity dropped 84.8 % in the MEUS + PEA-treated tumours when compared to 46.3 % (p < 0.05) in the PEA-treated tumours 24 h after treatment. The tumour necrosis rate of the combination therapy was 97.50 %, which is much higher than that of the MEUS- (66.2 %) and PEA-treated (81.0 %) tumours. CONCLUSION: PEA combined with MEUS can induce a much more complete tumour necrosis. KEY POINTS: * This experiment demonstrated a novel method for enhancing percutaneous ethanol ablation. * Microbubble-enhanced therapeutic ultrasound is capable of disrupting tumour circulation. * Combined therapy of MEUS and PEA can induce more complete necrosis of tumours. PMID- 26676562 TI - Evidence of a Christmas spirit network in the brain: functional MRI study. AB - OBJECTIVE: To detect and localise the Christmas spirit in the human brain. DESIGN: Single blinded, cross cultural group study with functional magnetic resonance imaging (fMRI). SETTING: Functional imaging unit and department of clinical physiology, nuclear medicine and PET in Denmark. PARTICIPANTS: 10 healthy people from the Copenhagen area who routinely celebrate Christmas and 10 healthy people living in the same area who have no Christmas traditions. MAIN OUTCOME MEASURES: Brain activation unique to the group with Christmas traditions during visual stimulation with images with a Christmas theme. METHODS: Functional brain scans optimised for detection of the blood oxygen level dependent (BOLD) response were performed while participants viewed a series of images with Christmas themes interleaved with neutral images having similar characteristics but containing nothing that symbolises Christmas. After scanning, participants answered a questionnaire about their Christmas traditions and the associations they have with Christmas. Brain activation maps from scanning were analysed for Christmas related activation in the "Christmas" and "non-Christmas" groups individually. Subsequently, differences between the two groups were calculated to determine Christmas specific brain activation. RESULTS: Significant clusters of increased BOLD activation in the sensory motor cortex, the premotor and primary motor cortex, and the parietal lobule (inferior and superior) were found in scans of people who celebrate Christmas with positive associations compared with scans in a group having no Christmas traditions and neutral associations. These cerebral areas have been associated with spirituality, somatic senses, and recognition of facial emotion among many other functions. CONCLUSIONS: There is a "Christmas spirit network" in the human brain comprising several cortical areas. This network had a significantly higher activation in a people who celebrate Christmas with positive associations as opposed to a people who have no Christmas traditions and neutral associations. Further research is necessary to understand this and other potential holiday circuits in the brain. Although merry and intriguing, these findings should be interpreted with caution. PMID- 26676563 TI - Tumor Specific Recruitment and Reprogramming of Mesenchymal Stem Cells in Tumorigenesis. AB - Non-neoplastic stromal cells harvested from patient tumors were identified as tumor-derived mesenchymal stem cells (MSCs) by their multipotential capacity to differentiate into adipocytes, osteoblasts, and chondrocytes and by the expression of MSC specific cell surface markers. These procedures yielded also epithelial cancer cells and their counterpart MSC from gastric carcinoma (GSC1) and lung carcinoma (LC2). While the LC2 cancer cell growth is independent of their LC-MSC, the GSC1 cancer cell growth is critically dependent on the presence of their counterpart GSC-MSC or their conditioned medium (CM). The fact that none of the various other tumor-derived MSCs was able to restore the specific effect of GSC-MSC on GSC1 cancer cell growth suggests specificity of tumor-derived MSC, which are specifically recruited and "educated"/reprogrammed by the cancer cells to support tumor growth. Using cytokine array analysis, we were able to demonstrate that GSC1 cell growth is mediated through hepatocyte growth factor (HGF)/c-MET signaling pathway which is activated exclusively by HGF secreted from GSC-MSC. An innovative approach demonstrates GSC1-mediated specific tropism of "naive" MSC from the adjacent tissue in a tumor specific manner to support tumor progression. The results suggest that specific tumor tropic "naive" MSC are reprogrammed in a tumor-specific manner to support gastric tumor progression. Understanding the mechanisms involved in the interactions of the tumor cancer cells and tumor-derived MSC will constitute the basis for developing multimodal anticancer therapeutic strategies that will also take into account the specific tumor tropism properties of MSC and their reprogramming. PMID- 26676564 TI - Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.). AB - BACKGROUND: Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. RESULTS: In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. CONCLUSION: The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. (c) 2015 Society of Chemical Industry. PMID- 26676565 TI - Generation of thioethers via direct C-H functionalization with sodium benzenesulfinate as a sulfur source. AB - A novel ammonium iodide-induced sulfenylation method of flavones, indole and arylimidazo[1,2-a]pyridines using stable and odorless sodium benzenesulfinates as sulfur sources was developed, generating regioselective derivatives in good yields. This method has enriched current thioether-producing methods and provided a good example of using ammonium iodide as a reaction inducer instead of iodine to make thioethers under environmentally friendly and odorless conditions. PMID- 26676566 TI - Time-dependent flow velocity measurement using two-dimensional color Doppler flow imaging and evaluation by Hagen-Poiseuille equation. AB - This paper aims to develop a technique to assess velocity flow profile and wall shear stress (WSS) spatial distribution across a vessel phantom representing an artery. Upon confirming the reliability of the technique, it was then used on a set of carotid arteries from a cohort of human subjects. We implemented color Doppler flow imaging (CDFI) for measurement of velocity profile in the artery cross section. Two dimensional instantaneous and time-dependent flow velocity and WSS vector fields were measured and their waveforms of peak velocities based on the technique were compared with WSS values generated by Hagen-Poiseuille equation. Seventy-five patients with intima-media thickening were prospectively enrolled and were divided into an IMT group. At the same time, another 75 healthy volunteers were enrolled as the control group. All the subjects were scanned and the DICOM files were imported into our in-house program. Next, we determine the velocity profile of carotid arteries in a set of 150 human subjects and compared them again. The peak velocities by the CDFI and Hagen-Poiseuille equation techniques were compared and statistically evaluated. The amounts of deviation for the two measured WSS profiles were performed and we demonstrated that they are not significantly different. At two different flow settings with peak flow velocity of 0.1, 0.5 (*10(-11)) m/s, the obtained WSS were 0.021 +/- 0.04, 0.038 +/- 0.05 m/s, respectively. For the patient population study, the mean WSS value calculated by Hagen-Poiseuille equation was 2.98 +/- 0.15 dyne/cm(2), while it was 2.31 +/- 0.14 dyne/cm(2) by our CDFI analysis program. The difference was not statistically significant (t = -1.057, P = 0.259). Similar to the Hagen Poiseuille equation, a negative linear correlation was also found between the calculated WSS and intima-media thickness (P = 0.000). Using CDFI analysis, we found that the WSS distribution at the middle of the proximal plaque shoulder was larger than the top of the shoulder. CDFI can assess the velocity and WSS profile accurately and efficiently and may be used for clinical diagnosis of cardiovascular conditions. PMID- 26676567 TI - Role of autophagy on bone marrow mesenchymal stem-cell proliferation and differentiation into neurons. AB - The purpose of the present study was to investigate the role of autophagy on rat bone marrow mesenchymal stem cell (BMSC) proliferation, apoptosis and differentiation into neurons. After treatment with rapamycin, 3-methyladenine (3 MA) or chloroquine, the cell cycle, apoptosis, expression of neuron-specific enolase (NSE) and the mean fluorescence intensity (MFI) of Notch1 in BMSCs were examined by flow cytometry. The expression of microtubule-associated protein 2 (MAP2), Notch1 and Hes1 was investigated by western blot analysis. The results showed that after induction of autophagy using rapamycin, the proliferation of BMSCs was inhibited. Furthermore, the S-phase population was significantly decreased compared to that in the control group (P<0.05). In addition, the percentage of NSE-positive cells and the expression of MAP2 were significantly increased compared to those in the control group (P<0.05). The MFI of Notch1 was markedly upregulated compared to that in the control group (P<0.05). When autophagy was inhibited by 3-MA or chloroquine, the percentage of apoptotic cells and NSE-positive cells as well as the expression of MAP2 were markedly reduced compared to those in the control group (P<0.05). Furthermore, western blot analysis showed that Notch1 and Hes1 were decreased in the rapamycin-treated group, while they were not affected by 3-MA or chloroquine. The present study indicated that induction of autophagy in BMSCs decreased their S-phase population, promoted their differentiation into neurons and promoted the expression of NSE and MAP2. The mechanisms underlying this process may be linked to the regulation of autophagy-induced inhibition of the Notch1 signaling pathway. PMID- 26676568 TI - Sex-Specific Effects of Prenatal Stress on Bdnf Expression in Response to an Acute Challenge in Rats: a Role for Gadd45beta. AB - Exposure to early adversities represents a major risk factor for psychiatric disorders. We have previously shown that exposure to prenatal stress (PNS) in rats alters the developmental expression of brain-derived neurotrophic factor (Bdnf) with a specific temporal profile. However, exposure to early-life stress is known to alter the ability to cope with challenging events later in life, which may contribute to the enhanced vulnerability to stress-related disorders. Since Bdnf is also an important player for activity-dependent plasticity, we investigated whether the exposure to PNS in rats could alter Bdnf responsiveness to an acute challenge at adulthood. We found that exposure to PNS produces significant changes in Bdnf responsiveness with brain region- and gender-specific selectivity. Indeed, exposure to an acute stress upregulates Bdnf expression in the prefrontal cortex, but not in the hippocampus, of control animals. Moreover, such modulatory activity is selectively impaired in PNS female rats, an effect that was associated with changes in the modulation of the DNA demethylase Gadd45beta. Our results suggest that exposure to PNS may reprogram gene transcription through epigenetic mechanisms reducing the ability to cope under adverse conditions, a trait that is disrupted in psychiatric diseases. PMID- 26676569 TI - Evaluation of the Acquisition of the Aerobic Metabolic Capacity by Myelin, during its Development. AB - Our previous reports indicate that the electron transfer chain and FoF1-ATP synthase are functionally expressed in myelin sheath, performing an extra mitochondrial oxidative phosphorylation (OXPHOS), which would provide energy to the nerve axon. This supports the idea that myelin plays a trophic role for the axon. Although the four ETC complexes and ATP synthase are considered exquisite mitochondrial proteins, they are found ectopically expressed in several membranous structures. This study was designed to understand when and how the mitochondrial OXPHOS machinery is embedded in myelin, following myelinogenesis in the rat, which starts at birth and continues until the first month of age. Rats were sacrificed at different time points (from day 5 to 90 post birth). Western blot, immunofluorescence microscopy, luminometric, and oximetric analyses show that the isolated myelin starts to show OXPHOS components around the 11th day after birth and increases proportionally to the rat age, becoming similar to those of adult rat around the 30-third day. Interestingly, WB data show the same temporal relationship between myelinogenesis and appearance of proteins involved in mitochondrial fusion and cellular trafficking. It may be speculated that the OXPHOS complexes may be transferred to the endoplasmic reticulum membrane (known to interact with mitochondria) and from there through the Golgi apparatus to the forming myelin membrane. PMID- 26676570 TI - MicroRNA-7 Enhances Subventricular Zone Neurogenesis by Inhibiting NLRP3/Caspase 1 Axis in Adult Neural Stem Cells. AB - alpha-Synuclein (alpha-syn) has been recognized to induce neuroinflammation and to disturb nerve repair process in Parkinson's disease. However, the potential mechanisms underlying alpha-syn-induced impairment of adult neurogenesis remain unclear. In the present study, A53T mutant alpha--synuclein transgenic (A53Ttg/tg) mice, caspase-1 knockout mice, and A53Ttg/tg;caspase-1-/- double transgenic mice were used to prepare adult neural stem cells (ANSCs) and to investigate inflammasome-related mechanism for alpha-syn-impaired neurogenesis in mouse subventricular zone (SVZ). We showed that alpha-syn inhibited neurogenesis in the SVZ of A53Ttg/tg mice and impaired proliferation and differentiation in ANSCs cultured in vitro, accompanied by reduced microRNA-7 (miR-7) expression levels. We further found that ANSC expressed NLRP3-containing inflammasome and alpha-syn activated both TLR4/NF-kappaB and NLRP3/caspase-1 signals in ANSCs. Either Nlrp3 knockdown or Caspase-1 knockout could attenuate the inhibition of proliferation in ANSCs induced by alpha-syn. Furthermore, we demonstrated that miR-7 post-transcriptionally controlled Nlrp3 expression besides targeting alpha syn. Most notably, stereotactic injection of miR-7 mimics into lateral ventricles significantly inhibited NLRP3 inflammasome activation and improved adult neurogenesis in mouse SVZ. Our study provides a direct link between NLRP3 inflammasome activation and alpha-syn-impaired neurogenesis in the pathogenesis of alpha-synucleinopathies. PMID- 26676571 TI - Efficacy of Progesterone for Acute Traumatic Brain Injury: a Meta-analysis of Randomized Controlled Trials. AB - Progesterone, a steroid hormone, has been shown to have multifactorial neuroprotective effects in a variety of animal models of acute traumatic brain injury (TBI). Translation to humans showed positive effects in previous phase II trials, but unfortunately, negative results were observed in two recent phase III trials. The present study focuses on the efficacy of progesterone on acute TBI based on the published data of randomized controlled trials (RCTs). MEDLINE, EMBASE, and Cochrane Library were used to search from January 1980 to August 2015 for English language studies. The primary outcome was a favorable outcome in the Glasgow outcome scale (GOS). The secondary outcomes included mortality and adverse events. A total of 2396 patients from 5 RCTs were included in the present study. There were no significant differences in favorable outcome (relative risk (RR) 1.07, 95 % confidence interval (CI) 0.91 to 1.27, P = 0.41) and mortality rate (RR 0.85, 95 % CI 0.65 to 1.13, P = 0.27) between progesterone and placebo groups. In a subgroup analysis, favorable outcome (RR 1.45, 95 % CI 1.11 to 1.89, P = 0.007) and decreased mortality rate (RR 0.58, 95 % CI 0.41 to 0.84, P = 0.004) are only observed in the phase II RCTs. The included factors were the severity of TBI, method of drug administration, and duration of observation and had no influence on the observed outcomes. Sensitivity analysis showed that all the outcomes were stable after excluding Shakeri (Clin Neurol Neurosurg 115: 2019 2022, 2013) or Wright (N Engl J Med 371: 2457-2466, 2014) trials. The quality of the evidence was varied from high to low. In conclusion, progesterone has no significant improvement in the functional recovery and mortality rate after acute TBI. PMID- 26676572 TI - The Pivotal Role of Ca2+ Homeostasis in PBDE-47-Induced Neuronal Apoptosis. AB - Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants and are ubiquitous in the environment and human tissues. Recent evidence has demonstrated that PBDE-induced neurotoxicity is associated with neuronal apoptosis via interfering with the calcium ion (Ca2+) homeostasis; however, the underlying mechanisms remain elusive. Thus, we sought to investigate the role of Ca2+ homeostasis in PBDE-47-induced neuronal apoptosis. Here, we showed that PBDE-47 significantly decreased neuronal number while increased neuronal apoptosis in vitro and in vivo, as manifested by an increased percentage of Annexin V-positive staining cells and caspase-3 activation in human neuroblastoma SH-SY5Y cells and hippocampal neurons of rats. Further study identified that PBDE-47 elicited DeltaPsim collapse following an early and sustained [Ca2+] i, overload, as well as stimulated cytochrome c release from mitochondria into the cytosol in SH-SY5Y cells and rat hippocampal tissue. Interestingly, the extracellular Ca2+ chelator ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) blocked PBDE-47-induced [Ca2+] i elevation, DeltaPsim collapse, cytochrome c release, and caspase-3 activation in SH-SY5Y cells, whereas the intracellular Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) had no influences on them, indicating that the [Ca2+] i overload originates primarily from extracellular Ca2+ component rather than from intracellular calcium storage and that the increase in [Ca2+] i is a major contributor to DeltaPsim collapse and subsequent neuronal apoptosis. Overall, these findings suggest that PBDE-47 affects Ca2+ homeostasis as a crucial event in activation of neuronal death associated with mitochondria and provide novel insight into the mechanism of action underlying PBDE neurotoxicity. PMID- 26676573 TI - Adrenoceptor-Mediated Post- and Pre-Synaptic Regulations of the Reticulospinal Neurons in Rat Caudal Pontine Reticular Nucleus. AB - The central noradrenergic system participates in diverse nervous functions. Nevertheless, our knowledge of the action of adrenoceptors in motor regulation is still lacking. Intriguingly, reticulospinal neurons in the caudal pontine reticular nucleus (PnC) receive fairly dense noradrenergic innervation and play an important role in motor control. Here, after demonstrating the expression of alpha1- and alpha2-adrenoceptors in the PnC, we found that noradrenaline elicited a post-synaptic effect (inward or outward whole-cell current at -70 mV holding) on PnC reticulospinal neurons. The alpha1- and alpha2-adrenoceptors were co expressed in individual PnC reticulospinal neurons to mediate an inward and an outward current component at -70 mV holding, respectively, which, when superposed, produced the overall post-synaptic effects of noradrenaline (NA). More importantly, the activation of post-synaptic alpha1- or alpha2-adrenoceptors indeed exerted opposing modulations (excitation vs. inhibition) on the firing activities of individual PnC reticulospinal neurons. Furthermore, the activation and inhibition of the Na+-permeable non-selective cationic conductance (NSCC) were demonstrated to be coupled to alpha1- and alpha2-adrenoceptors, respectively. Additionally, the activation of alpha2-adrenoceptors activated K+ conductance. Pre-synaptically, the alpha2-adrenoceptors were expressed to attenuate the miniature excitatory postsynaptic current (mEPSC) in PnC reticulospinal neurons, but not to affect the miniature inhibitory postsynaptic current (mIPSC). Consistently, the evoked EPSC in PnC reticulospinal neurons was suppressed after the activation of pre-synaptic alpha2-adrenoceptors. Thus, the excitatory input and post-synaptic dynamics of PnC reticulospinal neurons are indeed intricately modulated by the activation of alpha1- and alpha2 adrenoceptors, through which motor control may be regulated in an adaptive manner by the central noradrenergic system. PMID- 26676574 TI - Increased Wnt Signaling and Reduced Viability in a Neuronal Model of Progranulin Deficient Frontotemporal Lobar Degeneration. AB - Progranulin (PGRN) deficiency is considered the major cause of frontotemporal lobar degeneration with TDP-43 protein inclusions (FTLD-TDP). Recent work unveiled a relationship between Wnt signaling and PGRN in cellular models of FTLD and cells of patients carrying loss-of-function GRN mutations. This study was undertaken to explore the relationship between PGRN deficit and Wnt signaling in the regulation of survival of GRN knockdown neuroblastoma SH-SY5Y cells (GRN KD). We report here that both canonical and noncanonical Wnt signaling cascades are overactivated in GRN KD cells. We detected increased expression levels of Wnt1 and Wnt5a ligands of the Frizzled receptors, as well as evidence for increased signaling of the Wnt/beta-catenin and Wnt/Ca2+ cascades in PGRN deficient cells, such as increased nuclear content of beta-catenin and higher levels of cyclin D1, or increased levels of the active form of the NFAT1 transcription factor, respectively. Upregulation of either Wnt/beta-catenin or Wnt/Ca2+ signaling in GRN KD cells leads to the stimulation of BrdU incorporation into DNA, hyperphosphorylation of the pRb family of proteins and reduced cell viability over time. Blocking the Wnt cascades by specific canonical or noncanonical inhibitors of Wnt-dependent signaling, normalized the rate of DNA synthesis, and what it is more important restored the viability of GRN KD cells. Our results suggest an important role of Wnt activation inducing cell cycle disturbance mediated neuronal loss in the pathogenesis of PGRN deficiency-linked FTLD-TDP. Therefore, it is plausible that modulation of Wnt signaling could be a promising strategy for developing of new disease-modifying treatments for FTLD-TDP. PMID- 26676575 TI - The Potential Mutation of GAK Gene in the Typical Sporadic Parkinson's Disease from the Han Population of Chinese Mainland. AB - The genetic factors about the pathogenesis of sporadic Parkinson's disease (sPD) is not completely clear at present; therefore, we performed a genome-wide association study, high-throughput sequencing analysis (HTPSA) of all cyclin G associated kinase (GAK) exons, loss-of-function assessment, and sorting intolerant from tolerant analysis of HTPSA data in 250 typical sPD and 250 controls, which found 55 candidate single nucleotide polymorphisms (SNPs). To further explore these SNPs, we sequenced the 30 most strongly associated SNPs in the 460 typical sPD cases and the 525 controls. All subjects were from the Han population of Chinese mainland and excluded the toxic exposure, the heavy coffee drinking, and the early- and late-onset sPD. The minor allele frequencies (MAFs) at c.3824T>G, c.3794T>C, and c.3819G>A were higher in the control. The TG of c.3824T>G, the TC of c.3794T>C, and the AG of c.3819G>A were associated with the decreased risk of sPD. The subjects carrying the minor C allele of c.3794T>C or the minor A allele of c.3819G>A exhibited a decreased risk of sPD. c.3824T>G negatively affected the binding affinity of heat shock protein 70 (HSP70). c.3794T>C increased the surface area exposed to substrates. c.3819G>A most likely reduced the expression level of GAK. Our data suggest that the multiple SNPs of GAK synergistically participate in the pathogenesis of sPD through multiple pathways. PMID- 26676577 TI - Adopting ALK and LTK. PMID- 26676576 TI - Kinetics of nucleotide-dependent structural transitions in the kinesin-1 hydrolysis cycle. AB - To dissect the kinetics of structural transitions underlying the stepping cycle of kinesin-1 at physiological ATP, we used interferometric scattering microscopy to track the position of gold nanoparticles attached to individual motor domains in processively stepping dimers. Labeled heads resided stably at positions 16.4 nm apart, corresponding to a microtubule-bound state, and at a previously unseen intermediate position, corresponding to a tethered state. The chemical transitions underlying these structural transitions were identified by varying nucleotide conditions and carrying out parallel stopped-flow kinetics assays. At saturating ATP, kinesin-1 spends half of each stepping cycle with one head bound, specifying a structural state for each of two rate-limiting transitions. Analysis of stepping kinetics in varying nucleotides shows that ATP binding is required to properly enter the one-head-bound state, and hydrolysis is necessary to exit it at a physiological rate. These transitions differ from the standard model in which ATP binding drives full docking of the flexible neck linker domain of the motor. Thus, this work defines a consensus sequence of mechanochemical transitions that can be used to understand functional diversity across the kinesin superfamily. PMID- 26676578 TI - Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells. AB - Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein-glycan or protein-protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high affinity host-glycan:bacterial-glycan pairs with equilibrium dissociation constants (K(D)) ranging between 100 nM and 50 uM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems. PMID- 26676579 TI - A single protein redox ruler. PMID- 26676580 TI - Human behavior under economic inequality shapes inequality. PMID- 26676581 TI - Reply to Newman: Quantification of biological aging in young adults is not the same thing as the onset of obesity. PMID- 26676582 TI - Is the onset of obesity the same as aging? PMID- 26676583 TI - Reply to Rubenstein and Rubenstein: Time to move on from ideological debates on rewilding. PMID- 26676584 TI - From Pleistocene to trophic rewilding: A wolf in sheep's clothing. PMID- 26676585 TI - Reply to Melillo: Woranso-Mille is consistent with an australopithecine shoulder intermediate between African apes and Homo. PMID- 26676586 TI - An alternative interpretation of the Australopithecus scapula. PMID- 26676588 TI - Rectal eversion and coloanal anastomosis: a classical technique we should not forget--a video vignette. PMID- 26676587 TI - Bidirectional crosstalk via IL-6, PGE2 and PGD2 between murine myofibroblasts and alternatively activated macrophages enhances anti-inflammatory phenotype in both cells. AB - BACKGROUND AND PURPOSE: Alternatively activated macrophages (AAMs) are important cells in the resolution of inflammation and tissue repair. We examined the impact of myofibroblasts, a vital cell in wound healing and tissue repair, on the development and function of AAMs. EXPERIMENTAL APPROACH: The interaction between AAMs and myofibroblasts was tested using conditioned medium from murine dermal myofibroblasts and bone marrow-derived macrophages. AAMs were differentiated with IL-4 and IL-13. KEY RESULTS: Conditioned medium from myofibroblasts enhanced the expression of AAM markers, arginase 1 and Ym1 (chitinase-3-like 3) and the spontaneous production of IL-10, while suppressing LPS-induced nitric oxide production. IL-6 from the myofibroblasts contributed to the amplification of the AAM phenotype; the selective COX-2 inhibitor, NS-398, significantly reduced the ability of myofibroblasts to promote an AAM phenotype. Pharmacological analyses indicated that myofibroblast-derived IL-6 enhanced arginase activity and spontaneous IL-10 output, while PGE2 , via the EP4 receptor, enhanced arginase expression and LPS-evoked IL-10 production. PGD2 suppressed LPS-evoked nitric oxide via the DP1 receptor. Reciprocally, conditioned medium from macrophages treated with IL-4 + IL-13 and myofibroblast conditioned medium components, but not macrophages given IL-4 + IL-13 only, reduced myofibroblast migration, the expression of COX-2, and the production of PGE2 and PGD2 . CONCLUSIONS AND IMPLICATIONS: These findings define mechanisms by which myofibroblasts enhance an AAM phenotype, which can promote wound healing directly, and/or via feedback communication to the myofibroblast, subsequently down-regulating its capacity to promote AAM function. This is an important homeostatic regulatory pathway in wound healing that can also limit unwanted fibrosis. PMID- 26676590 TI - [Brazil's Unified Health System: between the intention and the reality]. PMID- 26676589 TI - Duration of Systemic Inflammation in the First Postnatal Month Among Infants Born Before the 28th Week of Gestation. AB - Extremely low gestational age newborns (ELGANs, <28 completed weeks of gestation) that exhibit fetal and neonatal systemic inflammatory responses are at increased risk for developmental adversity, especially if the inflammatory process is sustained. We evaluated pro-inflammatory cytokine patterns in whole blood of 1220 ELGANs on one or more of postnatal days 1, 7, 14, 21, and 28. Protein concentrations were divided into quartiles within gestational week categories. We calculated odds ratios (OR) with 99% confidence intervals (CI) for having a concentration in the top quartile for each protein given that the infant had a protein concentration in the top quartile 1 week or more earlier compared to infants who did not. ELGANs who have elevated systemic levels of IL-6R, TNF alpha, or RANTES on their first postnatal day are approximately twice as likely to have elevated levels of these cytokines at the end of each of the first postnatal month. In some, this twofold risk increase persisted for the entire first postnatal month. In extremely preterm newborns, inflammatory processes can be sustained over weeks. PMID- 26676591 TI - [Analysis of the impact of mortality due to suicides in Mexico, 2000-2012]. AB - The objective of this study was to analyze the burden of disease due to suicide in Mexico using years of life lost (YLL) between 2000 and 2012 by sex, age group (for those under 85 years of age) and jurisdiction. Vital statistics on mortality and population estimates were used to calculate standardized mortality rates and years of life lost due to suicide. Between 2000 and 2012 a sustained increase in the suicide mortality rate was observed in Mexico. The age group with the highest rate was 85 years of age or older for men, and 15-19 years of age for women. The highest impact in life expectancy due to suicide occurred at 20 to 24 years of age in men and 15 to 19 years of age in women. The states with the highest mortality due to suicide were located in the Yucatan Peninsula (Yucatan, Quintana Roo and Campeche). Mortality due to suicide in Mexico has increased continually. As suicides are preventable, the implementation of health public policies through timely identification, integral prevention strategies and the detailed study of associated risk factors is imperative. PMID- 26676592 TI - [Thinking about long-term care policies for Latin America]. AB - Latin America is aging. The process is occurring quickly and in unhealthy conditions with low levels of income. The number of older people who can no longer perform their daily activities will dramatically increase in the coming decades. Developed countries have already been facing this phenomenon over the last three decades, but Latin America has neither the resources nor the social protection systems of these countries. Formulating and planning health policies associated with this phenomenon should be a priority of the governments of Latin America. This paper defines what these care policies are, the models of care rich countries have developed, and the cost of such models. The situation in Latin America is then analyzed and conclusions and a series of discussions to address in the near future are proposed. PMID- 26676593 TI - [Violence and public health in the written press of Guadalajara, Mexico]. AB - This study seeks to describe how violence and its link to public health is represented in the written press of Guadalajara, Mexico. To this end, we carried out a mixed-content analysis of news pieces on violence published in the local sections of the four newspapers with greatest circulation in Guadalajara from the period of September 1 to 15, 2013. A total of 1,465 local news stories were reviewed, of which 399 were identified as being about violence. Of these, only 103 included healthcare aspects in their contents, generally making reference to medical services. The contents of these press articles did not identify violence as a critical public health issue, but rather as a safety issue affecting the community. PMID- 26676594 TI - [Excess weight and disability among the elderly in Argentina]. AB - The aim of this paper is to analyze the relationship between excess weight and the condition of disability among elderly people in Argentina and to assess the extent to which a protective factor could be operating that reduces or mitigates the effect of overweight on the loss of functional skills in people over 64 years of age. In order to do so, microdata from Argentina's 2009 National Survey of Risk Factors [Encuesta Nacional de Factores de Riesgo] was utilized. To measure the association among overweight, obesity and disability status, as well as the interaction of weight status and age, logistic regression models were estimated. The results indicate that although overweight and obesity have a positive net effect on the occurrence of disabilities, this effect is lower among people 64 years of age and older. This result could be suggesting that among older people a protective factor is at work that, while not reversing the direct relationship between excess weight and disability, seems to attenuate it. PMID- 26676595 TI - [Reflections on the conceptualization and measurement of access to health services in Argentina: The case of the National Survey of Risk Factors 2009]. AB - In this article we reflect on the complexity surrounding the conceptualization and measurement of access to health services. We present the theoretical models habitually used to approach the issue and different ways of operationalizing these models, taking into account the implications for the analysis of the data and the information obtained. As an example of this complexity, we analyze the National Survey of Risk Factors [Encuesta Nacional de Factores de Riesgo] conducted in Argentina in 2009. We show that the survey provides important information for understanding inequalities in access to health services. However, the way in which the barriers to access to the health system are measured may underreport the problem by only capturing extreme situations. PMID- 26676596 TI - [The health-disease-care process from the perspective of the users of a primary care clinic in Montevideo, Uruguay: An analysis of therapeutic trajectories]. AB - The aim of this paper is to analyze, using an ethnographic approach, the health disease-care experiences of the users of a multi-specialty clinic that forms part of the Metropolitan Primary Health Care Network of Uruguay's Public Health Services. The fieldwork was carried out in the northeast of Montevideo from July 2012 to November 2013, combining participant observation in social and care spaces and interviews with more than 20 users. In our analysis of care trajectories we found that people incorporate different practices and beliefs when facing their health problems. The use of biomedical health care services is predominant in Uruguay; nevertheless, people engage in self-care practices and in some cases, in the use of folk, religious/magical or alternative remedies. Medical pluralism is therefore observed in facing certain common ailments or significant experiences of disease. PMID- 26676597 TI - ["I was like a ticking bomb": Experiences of severe maternal morbidity in the Metropolitan Area of Buenos Aires]. AB - With the objective of recording and analyzing women's experiences with severe maternal morbidity from their perspective, between February and May 2011, 16 semi structured interviews with women treated in the public hospitals of the Buenos Aires Metropolitan Area who suffered from severe maternal morbidity were carried out. In their testimonies, women report a number of delays in care, such as difficulties in identifying the problem on time, obstacles in accessing health centers and important faults in the management of obstetric emergencies. They describe the event as surprising, distressing and painful, a perception reinforced by the violation of their rights and significant communication problems. These findings are meant as a step towards the holistic and comprehensive study of severe maternal morbidity, as well as to confirm the urgent need for further research from a gender and humans rights perspective. PMID- 26676598 TI - [Tobacco consumption and its relationship to the level of regular physical activity and physical fitness in adolescents from the region of Murcia (Spain)]. AB - This study looks at the relationship between tobacco consumption and the physical activity and fitness levels of adolescents. In a sample of 533 adolescents, both a questionnaire to obtain information regarding tobacco consumption and the International Physical Activity Questionnaire for information on physical activity were implemented; a battery of tests to assess physical fitness were also applied. Tobacco consumption was significantly higher in females (32.5%) than in males (25.7%). Levels of physical activity in both males and females were significantly associated with tobacco consumption (p<0.0005). Moreover, subjects who consumed tobacco showed lower overall averages in physical fitness tests than those who did not (4.26 vs. 5.77 in males and 4.54 vs. 6.71 in females). Tobacco consumption is therefore shown to be related to lower levels of physical activity and physical fitness in adolescents. PMID- 26676599 TI - [Qualitative analysis of water quality deterioration and infection by Helicobacter pylori in a community with high risk of stomach cancer (Cauca, Colombia)]. AB - This study looks at aspects of the environmental health of the rural population in Timbio (Cauca, Columbia) in relation to the deterioration of water quality. The information was obtained through participatory research methods exploring the management and use of water, the sources of pollution and the perception of water quality and its relation to Helicobacter pylori infection. The results are part of the qualitative analysis of a first research phase characterizing water and sanitation problems and their relation to emerging infectious diseases as well as possible solutions, which was carried out between November 2013 and August 2014. The results of this research are discussed from an ecosystemic approach to human health, recognizing the complexity of environmental conflicts related to water resources and their impacts on the health of populations. Through the methodology used, it is possible to detect and visualize the most urgent problems as well as frequent causes of contamination of water resources so as to propose solutions within a joint agenda of multiple social actors. PMID- 26676600 TI - Predictors of normal and abnormal outcome in clinical brain dopamine transporter imaging. AB - Brain dopamine transporter (DAT) imaging with [(123)I]FP-CIT SPECT can be used to evaluate the integrity of the mesostriatal dopaminergic system in patients with clinically uncertain parkinsonism. To evaluate whether scanning a patient is clinically necessary, it is vital to understand possible factors that affect the scanning result. Therefore, we investigated an unselected sample of 538 consecutively scanned patients from a 6-year period, and the demographic data and indications for DAT SPECT were recorded. After scanning, the patients were divided into groups according to the scanning outcome. Multivariate binary logistic regression analyses were performed to investigate whether the pre imaging variables had independent associations with the outcome of the scan. Three hundred and three (56.3 %) patients had abnormal scans showing a dopaminergic deficit. The independent factors associated with abnormal scans were older age (p = 0.002), asymmetry of motor symptoms (p = 0.005) and shorter symptom duration (p < 0.001). Re-evaluation of the previously established Parkinson's disease diagnosis was associated with a higher probability of an abnormal scan (74.4 % abnormal, p = 0.004), whereas the possibility of medication induced parkinsonism was associated with a higher probability of a normal scan (35.4 %, p = 0.036). The probability of an abnormal outcome in clinical brain DAT imaging increases with known risk factors of neurodegenerative parkinsonism. However, a long duration of uncertain motor symptoms and suspicion of medication induced parkinsonism are associated with a higher probability of a normal outcome. The findings reflect epidemiological factors in parkinsonism together with referral biases that may be used to improve the clinical use of DAT imaging. PMID- 26676602 TI - [In Process Citation]. PMID- 26676601 TI - Size-Dependent Toxicity of Gold Nanoparticles on Human Embryonic Stem Cells and Their Neural Derivatives. AB - This study explores the use of human embryonic stem cells (hESCs) for assessing nanotoxicology, specifically, the effect of gold nanoparticles (AuNPs) of different core sizes (1.5, 4, and 14 nm) on the viability, pluripotency, neuronal differentiation, and DNA methylation of hESCs. The hESCs exposed to 1.5 nm thiolate-capped AuNPs exhibit loss of cohesiveness and detachment suggesting ongoing cell death at concentrations as low as 0.1 MUg mL(-1). The cells exposed to 1.5 nm AuNPs at this concentration do not form embryoid bodies but rather disintegrate into single cells within 48 h. Cell death caused by 1.5 nm AuNPs also occur in hESC-derived neural progenitor cells. None of the other nanoparticles exhibit toxic effects on the hESCs at concentrations as high as 10 MUg mL(-1) during a 19 d neural differentiation period. Thiolate-capped 4 nm AuNPs at 10 MUg mL(-1) cause a dramatic decrease in global DNA methylation (5 mC) and a corresponding increase in global DNA hydroxymethylation (5 hmC) of the hESC's DNA in only 24 h. This work identifies a type of AuNPs highly toxic to hESCs and demonstrates the potential of hESCs in predicting nanotoxicity and characterizing their ability to alter the DNA methylation and hydroxymethylation patterns in the cells. PMID- 26676604 TI - Academic clinical research: Death by a thousand clicks. AB - Select strategies can reduce the administrative burden on researchers and improve efficiency without impeding clinical and regulatory goals. PMID- 26676603 TI - Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma. AB - IMPORTANCE: Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES: To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES: The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS: In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02 3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE: Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation. PMID- 26676605 TI - Comment on "Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity" and "Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination". AB - New insights into toxicity of dengue virus protein NS1 provide context to previous work and prompt further questions. PMID- 26676606 TI - Response to comment on "Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity" and "Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination". AB - Multiple risk factors may cause progression to severe dengue. PMID- 26676607 TI - The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection. AB - Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central trigger for production of anti perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic exosome-like vesicles triggered the production of anti-perlecan antibodies in naive mice and enhanced anti-perlecan antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility complex)-incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation. PMID- 26676608 TI - Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. AB - Psoriasis is a chronic inflammatory skin disease characterized by a relapsing remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Synthetic biology-based gene circuits are uniquely suited for the treatment of diseases with complex dynamics, such as psoriasis, because they can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins. We designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients. Implants of microencapsulated cytokine converter transgenic designer cells were insensitive to simulated bacterial and viral infections as well as psoriatic-unrelated inflammation. The designer cells specifically prevented the onset of psoriatic flares, stopped acute psoriasis, improved psoriatic skin lesions and restored normal skin-tissue morphology in mice. The antipsoriatic designer cells were equally responsive to blood samples from psoriasis patients, suggesting that the synthetic cytokine converter captures the clinically relevant cytokine range. Implanted designer cells that dynamically interface with the patient's metabolism by detecting specific disease metabolites or biomarkers, processing their blood levels with synthetic circuits in real time, and coordinating immediate production and systemic delivery of protein therapeutics may advance personalized gene- and cell-based therapies. PMID- 26676611 TI - Genomic prediction of growth in pigs based on a model including additive and dominance effects. AB - Independent of whether prediction is based on pedigree or genomic information, the focus of animal breeders has been on additive genetic effects or 'breeding values'. However, when predicting phenotypes rather than breeding values of an animal, models that account for both additive and dominance effects might be more accurate. Our aim with this study was to compare the accuracy of predicting phenotypes using a model that accounts for only additive effects (MA) and a model that accounts for both additive and dominance effects simultaneously (MAD). Lifetime daily gain (DG) was evaluated in three pig populations (1424 Pietrain, 2023 Landrace, and 2157 Large White). Animals were genotyped using the Illumina SNP60K Beadchip and assigned to either a training data set to estimate the genetic parameters and SNP effects, or to a validation data set to assess the prediction accuracy. Models MA and MAD applied random regression on SNP genotypes and were implemented in the program Bayz. The additive heritability of DG across the three populations and the two models was very similar at approximately 0.26. The proportion of phenotypic variance explained by dominance effects ranged from 0.04 (Large White) to 0.11 (Pietrain), indicating that importance of dominance might be breed-specific. Prediction accuracies were higher when predicting phenotypes using total genetic values (sum of breeding values and dominance deviations) from the MAD model compared to using breeding values from both MA and MAD models. The highest increase in accuracy (from 0.195 to 0.222) was observed in the Pietrain, and the lowest in Large White (from 0.354 to 0.359). Predicting phenotypes using total genetic values instead of breeding values in purebred data improved prediction accuracy and reduced the bias of genomic predictions. Additional benefit of the method is expected when applied to predict crossbred phenotypes, where dominance levels are expected to be higher. PMID- 26676609 TI - Therapeutic targeting of casein kinase 1delta in breast cancer. AB - Identification of specific drivers of human cancer is required to instruct the development of targeted therapeutics. We demonstrate that CSNK1D is amplified and/or overexpressed in human breast tumors and that casein kinase 1delta (CK1delta) is a vulnerability of human breast cancer subtypes overexpressing this kinase. Specifically, selective knockdown of CK1delta, or treatment with a highly selective and potent CK1delta inhibitor, triggers apoptosis of CK1delta expressing breast tumor cells ex vivo, tumor regression in orthotopic models of triple-negative breast cancer, including patient-derived xenografts, and tumor growth inhibition in human epidermal growth factor receptor 2-positive (HER2(+)) breast cancer models. We also show that Wnt/beta-catenin signaling is a hallmark of human tumors overexpressing CK1delta, that disabling CK1delta blocks nuclear accumulation of beta-catenin and T cell factor transcriptional activity, and that constitutively active beta-catenin overrides the effects of inhibition or silencing of CK1delta. Thus, CK1delta inhibition represents a promising strategy for targeted treatment in human breast cancer with Wnt/beta-catenin involvement. PMID- 26676610 TI - Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration. AB - Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, with each electrode acting as a pixel. Unintended stimulation of retinal ganglion cell axons causes patients to see large oblong shapes of light, rather than focal spots, making it difficult to perceive forms. To address this problem, we performed calcium imaging in isolated retinas and mapped the patterns of cells activated by different electrical stimulation protocols. We found that pulse durations two orders of magnitude longer than those typically used in existing implants stimulated inner retinal neurons while avoiding activation of ganglion cell axons, thus confining retinal responses to the site of the electrode. Multielectrode stimulation with 25-ms pulses can pattern letters on the retina corresponding to a Snellen acuity of 20/312. We validated our findings in a patient with an implanted epiretinal prosthesis by demonstrating that 25-ms pulses evoke focal spots of light. PMID- 26676612 TI - Two new bicyclic sulfoxides from Welsh onion. AB - Newly identified bicyclic sulfoxides, welsonins A1 (1) and A2 (2), were isolated from acetone extracts of the bulbs of the Welsh onion (Allium fistulosum). In this study, the structures of 1 and 2, which are tetrahydrothiophene-S-oxide derivatives, were characterized by spectroscopic analysis. These compounds appeared to be derived from the coupling of 1-propenyl sulfenic acid and uronic acid. Welsonin A1 (1) showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of alternatively activated M2 macrophages. PMID- 26676613 TI - Are we ready for day-case partial nephrectomy? AB - Fast-track and day-case surgeries are gaining more and more importance. Their development was eased by the diffusion of minimal invasive surgical strategies and the consequential morbidity reduction. In the field of kidney cancer, seven cases of ambulatory radical nephrectomy were previously reported in the international literature. Regarding robotic partial nephrectomy (PN), short postoperative pathways resulting in patients' discharge on postoperative day 1 were shown to be safe and feasible. We report our initial experience of robot assisted PN discharged on postoperative day zero and discuss the criteria for adequate patient selection. Indeed, outpatient PN will obviously not be suitable for all patients, and careful selection will be mandatory. Both specific baseline patient's factors and postoperative events will have to be recognized for the first ones and prevented for the second ones. Safety, patient satisfaction, cost efficiency, and reproducibility will be the key factors to assess and promote day case PN. PMID- 26676615 TI - Learning from Past Studies. PMID- 26676616 TI - Tadalafil for the Treatment of Lower Urinary Tract Symptoms in Japanese Men with Benign Prostatic Hyperplasia: Results from a 12-week Placebo-controlled Dose finding Study with a 42-week Open-label Extension. AB - OBJECTIVES: To examine the efficacy, safety, and dose response of tadalafil once daily in Japanese men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS). METHODS: Men >=45 years with moderate-to-severe BPH-LUTS were randomized to once-daily placebo (N = 140), tadalafil 2.5 mg (N = 142), or tadalafil 5.0 mg (N = 140), in a 12-week double-blind phase, followed by a 42-week, tadalafil 5.0 mg open-label extension (OLE) phase (N = 394). The primary outcome was total International Prostate Symptom Score (IPSS) change from baseline to last available observation in the double-blind phase. RESULTS: The least squares (LS) mean difference between placebo and tadalafil in total IPSS change from baseline was -0.7 (P = 0.201) and -1.1 (P = 0.062) for tadalafil 2.5 and 5 mg, respectively (ANCOVA; a dose-dependent improvement in placebo-adjusted total IPSS for tadalafil 5 mg versus 2.5 mg of 57%). Repeated-measures analyses identified a significant total IPSS change for tadalafil 5 mg (LS mean difference between placebo and tadalafil 5 mg: -1.2; P = 0.035), but not tadalafil 2.5 mg, at week 12. Significant improvements for tadalafil 5 mg were demonstrated (ANCOVA) for IPSS obstructive subscore (P = 0.033) and IPSS quality of life index (P = 0.022). Numerical improvements in IPSS scores were maintained over the OLE phase. Tadalafil was well tolerated with no unexpected adverse events. CONCLUSION: Tadalafil (5.0 mg) had a favorable benefit-to-risk profile, supporting further investigation of tadalafil (5.0 mg) in Japanese men with BPH LUTS. PMID- 26676614 TI - Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis. AB - INTRODUCTION: Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT. MATERIALS AND METHODS: We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis. RESULTS: For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0-76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6-22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6-8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients. CONCLUSIONS: Patients might benefit from subsequent treatment lines independently from treatment response in first line. PMID- 26676617 TI - Effects of the REMEEX System in Female Patients with Intrinsic Sphincteric Deficiency and Recurrent Urinary Incontinence: 3-Year Outcomes. AB - OBJECTIVES: To evaluate the long-term outcomes of the REMEEX system (EXternal MEchanical REgulation, Neomedic International, Terrassa, Barcelona, Spain) for the treatment of recurrent urinary incontinence (UI) and intrinsic sphincteric deficiency (ISD). METHODS: From August 2006 to September 2007, a total of 30 patients underwent REMEEX system. Patients were categorized into failed UI (Group A, 11 patients) and ISD (Group B, 19 patients). The success rate of patients after surgery was assessed by cure and satisfaction rates postoperatively at follow-up at 1, 12, and 36 months. Clinical, urodynamic, perioperative, and postoperative data of success rates were analyzed. RESULTS: Total cure rates with REMEEX system(Group A/Group B) were 100.0/94.7% at 1 month and 90.9/79.0% at 3 years. Satisfaction rates were 100.0/89.5% at 1 month and 81.8/68.4% at 3 years in groups A and B. Two patients (6.7%) experienced wound infections. Of these, one patient was treated using intravenous antibiotics and the other had their varitensor removed. Other minimal postoperative complications were immediately resolved. CONCLUSION: The REMEEX system may be an effective procedure regardless of previous incontinence surgical interventions and ISD. The correct sling tension is easily achieved during the early postoperative period, and when necessary, is able to convert late failures into cures. The problems of recurrent UI during the follow-up period were also resolved successfully in every case. PMID- 26676618 TI - Do Sacral/Peripheral Lesions Contribute to Detrusor-Sphincter Dyssynergia? AB - OBJECTIVES: While detrusor-sphincter dyssynergia (DSD) occurs in conjunction with lesions between the brainstem and the sacral cord, it is not well known whether sacral/peripheral lesions contribute to DSD. We studied the relationship between DSD and sacral/peripheral lesions. METHODS: One hundred and forty-four patients with diverse neurologic etiologies underwent urodynamic study and analysis of motor unit potentials in the external sphincter muscles, 117 of whom were able to void during a urodynamic test. Sacral/peripheral lesion (SPL) is defined as neurogenic change in motor unit potentials. Detrusor overactivity (DO) is defined as involuntary detrusor contractions during the filling phase, which commonly occurs in lesions above the sacral cord. We considered DO as a putative indicator of supra-sacral lesion. RESULTS: DSD was found in 44 (30.6%), SPL in 71 (49.3%), and DO in 83 (57.6%) of 144 patients, respectively. The incidence of DSD was the same in the SPL positive group (31%) and the SPL negative group (30.1%). By contrast, within the subgroup of patients without DO, the incidence of DSD was significantly more common in the SPL positive group (41.4%) than in the SPL negative group (25.0%) (P < 0.05). In 53 of the SPL positive group who were able to void, postvoid residual >100 mL was more common in patients with DSD (not statistically significant). CONCLUSION: The results of the present study suggest that not only suprasacral pathology, but also sacral/peripheral lesions can produce DSD. In light of the previous reports, DSD might also result from partial lesions in peripheral branches of the sphincter circuit. PMID- 26676619 TI - Effect of Imidafenacin before Sleeping on Nocturia. AB - OBJECTIVES: Clinical efficacy, influence on quality of life (QOL), and safety of imidafenacin before sleeping were assessed in patients with overactive bladder (OAB) who suffered from nocturia. METHODS: A total of 60 OAB patients with a mean age of 74 years (45 men and 15 women) who mainly complained of nocturia were enrolled. Imidafenacin (0.1 mg) was administered once daily before sleeping for four weeks. Then the patients were divided into two groups, "a stable-dose group" with sufficient efficacy who remained on 0.1 mg of imidafenacin daily, and "a dose-escalation group" with insufficient efficacy in whom the daily dose of imidafenacin was increased to 0.2 mg before sleeping. Lower urinary tract symptoms and postvoid residual volume (PVR) were examined before treatment and after 4 and 8 weeks of imidafenacin therapy. RESULTS: In the stable-dose group, nighttime frequency decreased significantly from 3.4 +/- 1.1 to 2.3 +/- 1.1 and 2.6 +/- 2.0 times after four and eight weeks, respectively. In the dose escalation group, nighttime frequency did not change significantly (from 3.8 +/- 1.5 to 3.6 +/- 1.8 times) at four weeks, but decreased significantly to 2.8 +/- 1.4 times at eight weeks. Daytime frequency, OAB symptom score, and IPSS-QOL index score were significantly improved in both groups at four and/or eight weeks. There was no increase of PVR and no serious adverse events. CONCLUSION: Administration of imidafenacin at 0.1-0.2 mg once daily before sleeping was safe and effective for the treatment of OAB with the main symptom of nocturia. PMID- 26676620 TI - Comparison of Naftopidil 75 mg with Tamsulosin Hydrochloride 0.2 mg in the Treatment of Lower Urinary Tract Symptoms with Benign Prostatic Hyperplasia. AB - OBJECTIVE: To compare the efficacy of two alpha1 -adrenoceptor antagonists, alpha1D -adrenoceptor-selective naftopidil (Naf) 75 mg and alpha1A -adrenoceptor selective tamsulosin hydrochloride (Tam) 0.2 mg, for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). METHODS: Seventy-seven patients with LUTS secondary to BPH were enrolled. Data were gathered from patients retrospectively: 41 patients who were prescribed Naf 75 mg for 4 weeks and 36 patients who were prescribed Tam 0.2 mg for 4 weeks, respectively. The efficacy criteria were improvement in LUTS International Prostate Symptom Score (IPSS) and quality of life (QOL) scores after dosing. RESULTS: Naf 75 mg significantly improved symptoms in all 11 categories (overall IPSS, incomplete emptying, voiding symptoms [Intermittency, poor flow and straining], storage symptoms [daytime frequency, urgency and nocturia frequency], QOL index, intermittency, poor flow, straining, daytime frequency, urgency, and nocturia frequency) (P < 0.05). Tam 0.2 mg significantly suppressed 10 of the 11 tested symptom categories except straining (P < 0.05). Comparison data of the two drugs tended to show Naf 75 mg had better efficacy on nocturia frequency than Tam 0.2 mg (P < 0.05). CONCLUSION: Naf 75 mg might show a better efficacy for LUTS with BPH in nocturia frequency than Tam 0.2 mg. PMID- 26676621 TI - Apremilast in the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Pilot Study. AB - OBJECTIVE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease with an uncertain cause and limited effective treatments. Apremilast (Celgene Corporation, Summit, NJ, USA) is a selective phosphodiesterase type 4 (PDE4) inhibitor that modulates the immune system. An open-label, one-arm, pilot study was conducted to explore its potential for improving CP/CPPS symptoms. METHODS: Males >= 18 years of age were treated with 20 mg oral apremilast twice daily for up to 12 weeks. Outcomes were measured with Global Response Assessment (GRA), pain visual analog scale (VAS), Chronic Prostatitis Symptom Index (CPSI), Pittsburgh Sleep Quality Index (PSQI), SF-12 mental (MCS) and physical (PCS) health-related quality of life subscales, and voiding diaries. Repeated measures and paired t-tests evaluated changes from baseline to end of treatment, and at a final visit 4 weeks off the drug. RESULTS: Seventeen men (94% Caucasian; mean age 48.2 +/- 10 years) were treated (mean 115.8 +/- 56.1 doses). Mean VAS (3.4 +/- 2.0 vs 1.8 +/- 1.7; P = 0.0011), PSQI (9.4 +/- 4.4 vs 7.4 +/- 4.2; P = 0.037) and CPSI (26.1 +/- 5.0 vs 17.2 +/- 8.3; P = 0.0016) scores improved from baseline to end of treatment. Incontinence episodes per day improved slightly (P = 0.042). When only those completing at least 8 weeks of treatment were examined (n = 9), significant changes in CPSI, VAS, and PSQI were still observed. At the final visit, 8/9 (88.9%) men also reported some improvement in pain related to sex. Side-effects were generally mild and well tolerated. CONCLUSION: These results suggest that apremilast may improve CP/CPPS symptoms with only mild side-effects. However, placebo controlled studies are necessary to determine efficacy. PMID- 26676622 TI - Relationship between Toe Temperature and Lower Urinary Tract Symptoms. AB - OBJECTIVE: Cold stress can elicit increases in urinary urgency and frequency. We determined if there was a relationship between finger and toe temperatures and lower urinary tract symptoms (LUTS). METHODS: We studied 50 people who visited a public health management seminar. The participants were divided into two groups according to self-described sensitivity to cold stress. The cold non-sensitive (CNS) group consisted of 3 males and 20 females (66.9 +/- 10.8 years old), and the cold sensitive (CS) group consisted of 4 males and 23 females (65.8 +/- 8.01 years old). Each participant was assessed to determine international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and quality of life (QOL) score. They were then instructed on lifestyle changes and exercises that could improve peripheral blood flow and provide relief for their LUTS. Next, the temperatures of their middle fingers and toes were measured before and after 5-10 min of the exercises. Two weeks later, the IPSS, OABSS, and QOL scores were reassessed. RESULTS: Before exercise, the middle fingers were significantly warmer than the middle toes. Exercise had no significant effect on the middle finger temperature of either group; however, it did increase the middle toe temperature for both groups. The increase was greatest for the CS group. The CS group had higher LUTS storage symptoms than the CNS group, and these improved after 2 weeks of lifestyle changes and exercise. CONCLUSION: Improvements in lifestyle and daily exercise may be effective for LUTS in CS people. PMID- 26676623 TI - Modulation of Bladder Afferent Activity by Propiverine and its Active Metabolites (M-1 and M-2) in Rats. AB - OBJECTIVES: To evaluate the effects of propiverine and its active metabolites (M 1 and M-2) on bladder function through modulation of afferent activity in rats. METHODS: Cystometry was performed in urethane anesthetized female rats. We examined the effects of intravesical administration of propiverine, M-1 and M-2 on bladder overactivity induced by oxotremorine-M (Oxo-M; non-selective mAChR agonist). RESULTS: Intravesical administration of Oxo-M (200 uM) elicited bladder overactivity as evidenced by decreased intercontraction interval (ICI) and pressure threshold (PT) without changing maximum voiding pressure or baseline pressure. These effects were blocked by intravesical administration of propiverine (30 uM) or M-2 (300 uM). Intravesical administration of M-1 (30 uM) alone increased ICI and PT, but did not prevent Oxo-M-induced decreases in ICI and PT. CONCLUSION: These results suggest that propiverine and M-2 have anticholinergic effects on bladder afferent activity and that M-1 has an inhibitory effect through the mechanism other than muscarinic receptor modulation. Thus, clinical benefits of propiverine in patients with overactive bladder could be mediated by multiple actions of propiverine and its active metabolites. PMID- 26676624 TI - Stromal Cell-Derived Factor 1alpha Induces Accumulation of Intraveneously Administered Marrow-Derived Stromal Cells in the Partially Obstructed Rat Bladder. AB - OBJECTIVES: We investigated the time course of the stromal cell-derived factor 1alpha (SDF1alpha) expression and behavior of intravenously administered bone marrow-derived stromal (BMS) cells in the urinary bladder of partial bladder outlet obstruction (PBOO) rats. METHODS: Study 1: Recombinant SDF1alpha or saline was directly injected into the bladder wall of female rats followed by intravenous administration of BMS cells isolated from green fluorescent protein (GFP) transgenic rats. The bladder was examined with immunohistochemistry to determine whether SDF1alpha would enhance migration of BMS cells to the bladder. Study 2: Following surgery of PBOO or sham in female rats, bladders were removed on days 1-14, and expression of hypoxia inducible factor 1alpha (HIF1alpha) and SDF1alpha were examined with real-time polymerase chain reaction (PCR) to determine if PBOO preferentially increased their expression. Study 3: Female rats underwent PBOO or sham surgery followed by intravenous administration of GFP positive BMS cells. Bladders were examined with immunohistochemistry on days 1-14 to determine whether BMS cells preferentially accumulated in the bladder. RESULTS: BMS cells were accumulated in the injection site of SDF1alpha but not saline in the bladder. SDF1alpha and HIF1alpha increased at day 1 after PBOO compared to sham. More BMS cells accumulated in the bladder of PBOO on day 1, and some BMS cells expressed smooth muscle phenotypes by day 14. CONCLUSION: SDF1alpha induced with ischemia/hypoxia due to PBOO is implicated in the accumulation of BMS cells in the bladder and regeneration of the bladder for PBOO. PMID- 26676625 TI - Brainstem Stroke and Increased Anal Tone. AB - After suffering a brainstem stroke, a 62-year-old man developed locked-in syndrome including loss of horizontal eye movement and increased anal tone. Magnetic resonance imaging (MRI) of the patient revealed a massive stroke in the pons and right cerebellum, which seemed to involve the pontine micturition/defecation center (Barrington's nucleus) and the rostral pontine reticular formation (RPRF). As his increased anal tone was intractable to medical treatment, he required intermittent catheterization with an anal bougie tube. In light of the reported cases, our patient developed increased anal tone presumably due to pontine defecation center and RPRF lesion. PMID- 26676626 TI - High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease. AB - BACKGROUND: Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk for chronic kidney disease (CKD); liver fibrosis with biopsy-proven NAFLD has also been shown to associate with an increased risk of CKD. This study compares the diagnostic performance of simple noninvasive tests in identifying prevalent CKD among individuals with ultrasonography-diagnosed NAFLD. METHODS: A total of 755 with ultrasonography diagnosed NAFLD were included. Estimated glomerular filtration rate and noninvasive markers for hepatic fibrosis: aspartate transaminase to alanine transaminase ratio (AAR), aspartate transaminase to platelet ratio index (APRI), FIB-4 score, NAFLD fibrosis score (NFS) and BARD score were assessed. RESULTS: Binary logistic regression to generate a propensity score and receiver operating characteristic curves were developed for each of the noninvasive markers for predicting CKD, and the area under the receiver operating characteristic curve was greatest for FIB-4 score (0.750), followed by NFS (0.710), AAR (0.594), APRI (0.587), and BARD score (0.561). A cut-off value of 1.100 for FIB-4 score gave a sensitivity of 68.85% and a specificity of 71.07% for predicting CKD. The positive predictive value and negative predictive value were 37.50 and 90.05%, respectively. In multiple logistic regression analysis, only FIB-4 score ?1.100 (OR 2.660, 95% CI 1.201-5.889; p = .016), older age, higher diastolic blood pressure and higher uric acid were independent predictors of CKD. CONCLUSIONS: High noninvasive fibrosis score is associated with an increased risk of prevalent CKD; the FIB-4 is the better predictor. With a cut-off value of 1.100 for FIB-4, it is useful in excluding the presence of CKD in patients with NAFLD. PMID- 26676627 TI - Whole-body synthesis of L-homoarginine in pigs and rats supplemented with L arginine. AB - Recent studies suggest an important role for L-homoarginine in cardiovascular, hepatic and neurological functions, as well as the regulation of glucose metabolism. However, little is known about whole-body L-homoarginine synthesis or its response to dietary L-arginine intake in animals. Four series of experiments were conducted to determine L-homoarginine synthesis and catabolism in pigs and rats. In Experiment 1, male and female pigs were fed a corn- and soybean meal based diet supplemented with 0.0-2.42 % L-arginine-HCl. In Experiment 2, male and female rats were fed a casein-based diet, while receiving drinking water containing supplemental L-arginine-HCl to provide 0.0-3.6 g L-arginine/kg body weight/day. In both experiments, urine collected from the animals for 24 h was analyzed for L-homoarginine and related metabolites. In Experiment 3, pigs and rats received a single oral dose of 1 or 10 mg L-homoarginine/kg body-weight, respectively, and their urine was collected for 24 h for analyses of L homoarginine and related substances. In Experiment 4, slices of pig and rat tissues (including liver, brain, kidney, heart, and skeletal-muscle) were incubated for 1 h in Krebs-bicarbonate buffer containing 5 or 50 uM L homoarginine. Our results indicated that: (a) animal tissues did not degrade L homoarginine in the presence of physiological concentrations of other amino acids; (b) 95-96 % of orally administered L-homoarginine was recovered in urine; (c) L-homoarginine was quantitatively a minor product of L-arginineg catabolism in the body; and (d) dietary L-arginine supplementation dose-dependently increased whole-body L-homoarginine synthesis. These novel findings provide a new framework for future studies of L-homoarginine metabolism and physiology in animals and humans. PMID- 26676628 TI - Driving Simulator Performance in Novice Drivers with Autism Spectrum Disorder: The Role of Executive Functions and Basic Motor Skills. AB - Previous studies have shown that individuals with autism spectrum disorder (ASD) demonstrate poorer driving performance than their peers and are less likely to obtain a driver's license. This study aims to examine the relationship between driving performance and executive functioning for novice drivers, with and without ASD, using a driving simulator. Forty-four males (ages 15-23), 17 with ASD and 27 healthy controls, completed paradigms assessing driving skills and executive functioning. ASD drivers demonstrated poorer driving performance overall and the addition of a working memory task resulted in a significant decrement in their performance relative to control drivers. Results suggest that working memory may be a key mechanism underlying difficulties demonstrated by ASD drivers and provides insight for future intervention programs. PMID- 26676629 TI - Restricted and Repetitive Behaviors as Predictors of Outcome in Autism Spectrum Disorders. AB - Questions have been raised about the significance of restricted and repetitive behaviors (RRBs) in predicting outcomes of children with Autism Spectrum Disorders (ASDs). Previous studies have yielded mixed findings, but some suggest that the presence of RRBs during preschool years is a negative prognostic indicator for later childhood. This study examined the effect of RRBs at ages 1-2 and 3-5 years on cognitive functioning, adaptive abilities, and ASD symptomatology at age 8-10 years in 40 children with ASDs. At 1-2 years, RRBs did not predict later functioning. However, at 3-5 years, more severe preoccupations with parts of objects, sensory interests, and stereotyped motor movements predicted less developed cognitive and adaptive skills, and greater ASD symptom severity at age 8-10 years. PMID- 26676630 TI - Loving and angry? Happy and sad? Understanding and reporting of mixed emotions in mother-child relationships by 6- to 12-year-olds. AB - The Evaluative Space Model of emotions allows for the coactivation of positive appetitive and negative-avoidant systems, but few studies have examined mixed emotions in child development. Existing research suggests children's understanding of opposite valence emotion combinations emerges by approximately 11 years of age. However, it is not yet clear whether various opposite valence combinations are understood at different ages, nor whether children can understand them in others before they have experienced such mixed emotions themselves. Semi-structured interviews with 97 children investigated whether they regarded six combinations of opposite valence mixed emotions as possible, could provide reasons for them, and report their own experience of each in the context of mother-child relationships. Both understanding that such combinations are possible and ability to provide reasons for them increased after age 6 and up to age 11, but were still incomplete in 12-year-olds. Understanding of different opposite valence combinations developed at different rates. At each age, fewer children who showed understanding of these combinations in others reported having had a similar experience themselves. The findings suggest a need to systematically examine a range of mixed emotions in order to develop a comprehensive theory of the development of mixed emotion understanding. They also suggest extending research into adolescence. PMID- 26676631 TI - [Influence of external pelvic stabilization on hemodynamically unstable pelvic fractures]. AB - BACKGROUND: In the treatment of complex pelvic fractures hemorrhage control is of primary importance; however, studies regarding the localization of bleeding are contradictory so that various treatment approaches are recommended. The primary aim of external pelvic compression applied in the trauma room is to reduce the pelvic volume and counteract blood loss through self-induced tamponade. This study examined the influence of external pelvic compression on mortality and outcome in cases of hemodynamically unstable pelvic fractures in a larger number of cases. MATERIAL AND METHODS: The current study used the TraumaRegister DGU(r) (TR-DGU) to retrospectively evaluate the records of 104 patients treated between 2002 and 2011. All patients suffered severe injury with an injury severity score (ISS) of at least 16 points. In addition, the patients were hemodynamically unstable with confirmed relevant isolated pelvic injuries. To evaluate the effectiveness of external pelvic compression, patients with and without external pelvic stabilization were compared. RESULTS: Of the investigated patients 26.9 % died of their injuries and of these the mortality was 78.6 % within the first 6 h of admission to the trauma room. External pelvic stabilization was performed in 45.2 % of patients. The mortality was 19.1 % in patients with external pelvic stabilization and in contrast, the mortality in the group of patients without external pelvic stabilization was 33.3 %. During the course of hospitalization, surviving patients with external pelvic stabilization were significantly more likely to develop sepsis or multiple organ failure and required longer periods of intensive care. CONCLUSION: External pelvic stabilization seems to be an important instrument for the initial treatment of hemodynamically unstable pelvic fractures and showed a positive effect on patient mortality. PMID- 26676632 TI - [FLS - three letters alter secondary fracture prevention]. AB - The increasing importance of preventive measures in the field of orthopedics and trauma surgery becomes apparent because of the demographic changes and the high risk for secondary fractures following osteoporotic fractures. Within the fracture treatment chain, orthopedics and trauma surgery are in the "pole position" to initiate these measures in geriatric patients. In the past orthopedists and trauma surgeons have constantly accused of neglecting secondary fracture prevention in fragility fracture patients. There are several reasons that speak in favor of us undertaking a role in secondary fracture prevention: osteoporosis medication is highly effective in fracture prevention when correctly indicated, the positive effects of osteoporosis therapy on fracture healing and legal issues. Arguments that have been used to justify neglect of secondary fracture prevention are undesired side effects related to osteoporosis medications, such as atypical femoral fractures and osteonecrosis of the jaws, interference of some specific drugs with fracture healing and the working conditions in emergency departments. These run contrary to the consideration of chronic diseases such as osteoporosis, secondary osteoporosis and the underlying disease could be overlooked and the increasing complexity of medicinal osteoporosis therapy. In the first part of the article these arguments are weighed against each other. In the second part the concept of a fracture liaison service (FLS) is discussed. The FLS framework now allows an active role to be taken with respect to secondary fracture prevention despite the busy daily routine schedule. Implementation of an FLS is facilitated by dedicated instruction protocols and programs. Self-financing of an FLS is currently possible only in some specific healthcare systems. In healthcare systems in German-speaking areas a cross-financing must be available and the value of an FLS indirectly presented. Apart from the financial aspects, implementation of a FLS is also worthwhile because it can be looked on as the future driving force of innovation. PMID- 26676633 TI - Vgamma9Vdelta2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma. AB - Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vgamma9Vdelta2 T cells. However, whether ZOL-stimulated Vgamma9Vdelta2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vgamma9Vdelta2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 MUM) and IL-2 (400 IU/ml). The antitumor activity of Vgamma9Vdelta2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vgamma9Vdelta2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vgamma9Vdelta2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vgamma9Vdelta2 T cells inhibited subcutaneous xenograft growth. Thus, Vgamma9Vdelta2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vgamma9Vdelta2 T cells for CS treatment. PMID- 26676634 TI - Hyperoside induces apoptosis and inhibits growth in pancreatic cancer via Bcl-2 family and NF-kappaB signaling pathway both in vitro and in vivo. AB - Although advanced surgical operation and chemotherapy have been under taken, pancreatic cancer remains one of the most aggressive and fatal human malignancies with a low 5-year survival rate of less than 5 %. Therefore, novel therapeutic strategies for prevention and remedy are urgently needed in pancreatic cancer. This present research aimed to investigate the anti-cancer effects of hyperoside in human pancreatic cancer cells. Our in vitro results showed that hyperoside suppressed the proliferation and promoted apoptosis of two different human pancreatic cancer cell lines, which correlated with up-regulation of the ratios of Bax/Bcl-2 and Bcl-xL and down-regulation of levels of nuclear factor-kappaB (NF-kappaB) and NF-kappaB's downstream gene products. What's more, using an orthotopic model of human pancreatic cancer, we found that hyperoside also inhibited the tumor growth significantly. Mechanically, these outcomes could also be associated with the up-regulation of the ratios of Bax/Bcl-2 and Bcl-xL and down-regulation of levels of NF-kappaB and NF-kappaB's downstream gene products. Collectively, our experiments indicate that hyperoside may be a promising candidate agent for the treatment of pancreatic cancer. PMID- 26676635 TI - The prevalence and clinical profiles of FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations in a cohort of patients with de novo acute myeloid leukemia from southwest China. AB - While a substantial amount of data on gene mutations related to acute myeloid leukemia (AML) prognosis from western and other populations have been reported, these studies largely describe one or two genes. Additionally, in southwest China, only insufficient data exist regarding FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations have been widely used in clinical settings. Therefore, a comprehensive study about these mutations of clinical importance in the prognosis of AML in western China is necessary. In a cohort of 255 patients with de novo AML, we retrospectively analyzed the prevalence of the six gene mutations, and then we assessed the results in conjunction with clinical characteristics and treatment responses. As for the frequencies of these mutations, the NPM1 mutation occurred most frequently (17.7 %; 42/237), followed by the CEBPA mutation (15.0 %; 19/127) and the FLT3-ITD mutation (10.2 %; 25/244). The frequencies of the FLT3-TKD, DNMT3A, and C-KIT mutations were 3.7 % (9/234), 4.0 % (9/225) and 4.2 % (10/238), respectively. These mutations were closely related to clinical characteristics including FAB classification, gender and age, hemogram, blasts (%), fusion genes, and immunophenotypes. Additionally, a higher complete remission (CR) rate was found in NPM1-mutated patients. The occurrence of these mutations is variable among different countries and regions worldwide, which may provide clues to the etiology of AML. Besides, we identified new clinical characteristics that advance our understanding of these mutations and further clarify the involvement of these mutations in the development of leukemia. PMID- 26676636 TI - Upregulated SMYD3 promotes bladder cancer progression by targeting BCLAF1 and activating autophagy. AB - The recent discovery of a large number of histone methyltransferases reveals important roles of these enzymes in regulating tumor development and progression. SMYD3, a histone methyltransferase, is associated with poor prognosis of patients with prostate and gastric cancer. In the study, we attempted to investigate its putative oncogenic role on bladder cancer. Here, we report that SMYD3 frequently amplified in bladder cancer is correlated with bladder cancer progression and poor prognosis. Overexpression of SMYD3 promotes bladder cancer cell proliferation and invasion, whereas SMYD3 knockdown inhibits cancer cell growth and invasion. Mechanically, SMYD3 positively regulates the expression of BCL2 associated transcription factor 1 (BCLAF1). SMYD3 physically interacts with the promoter of BCLAF1 and upregulates its expression by accumulating di- and trimethylation of H3K4 at the BCLAF1 locus. We further show that SMYD3 overexpression in bladder cancer cells promotes autophagy activation, whereas BCLAF1 depletion inhibits SMYD3-induced autophagy. Finally, we demonstrate that SMYD3 promotes bladder cancer progression, at least in part by increasing BCLAF1 expression and activating autophagy. Our results establish a function for SMYD3 in autophagy activation and bladder cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of bladder cancer. PMID- 26676637 TI - Reciprocal regulation of Hsa-miR-1 and long noncoding RNA MALAT1 promotes triple negative breast cancer development. AB - Recent studies demonstrated that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cancer progression and metastasis. However, little is known about the mechanism through which metastasis-associated lung adencarcinoma transcript 1 (MALAT1) exerts its oncogenic activity, and the interaction between MALAT1 and microRNA remains largely unknown. In the present study, we reported that MALAT1 was upregulated in triple-negative breast cancer (TNBC) tissues. Knockdown of MALAT1 inhibited proliferation, motility, and increased apoptosis in vitro. In vivo study indicated that knockdown of MALAT1 inhibited tumor growth and metastasis. Patients with high MALAT1 expression had poorer overall survival time than those with low MALAT1 expression. In addition, our findings demonstrate a reciprocal negative control relationship between MALAT1 and miR-1: downregulation of MALAT1 increased expression of microRNA-1 (miR-1), while overexpression of miR-1 decreased MALAT1 expression. Slug was identified as a direct target of miR-1. We proposed that MALAT1 exerted its function through the miR-1/slug axis. In summary, we proposed that MALAT1 may be a target for TNBC therapy. PMID- 26676638 TI - Overexpression of the transcription factor FOXP3 in lung adenocarcinoma sustains malignant character by promoting G1/S transition gene CCND1. AB - The Forkhead box P3 (FOXP3) transcription factor is the key driver of the differentiation and immunosuppressive function of regulatory T cells (Tregs). Additionally, FOXP3 has been reported to be expressed in many solid tumor cell lines and tissues. However, its role in tumorigenesis and tumor progression is conflicting, both tumor suppressive and promoting functions have been described. In this study, we demonstrated that FOXP3 was expressed in both lung adenocarcinoma tissues and the lung adenocarcinoma cell line A549. FOXP3 inhibition decreased cell proliferation, migration, and invasion as well as the secretion of inhibitory cytokines (e.g., transforming growth factor beta 1 (TGF beta1), interleukin 35 (IL-35), and heme oxygenase-1 (HMOX1)), suggesting a positive role for FOXP3 in tumor development. Importantly, we found that FOXP3 could enhance lung adenocarcinoma cell proliferation via upregulating the levels of the cell cycle G1/S checkpoint gene CCND1. These data demonstrated that FOXP3 could be regarded as a novel therapeutic target for inhibiting lung adenocarcinoma progression. PMID- 26676639 TI - The clinical utility of the proliferating cell nuclear antigen expression in patients with hepatocellular carcinoma. AB - Proliferating cell nuclear antigen (PCNA) has been suggested as a potential diagnostic biomarker for early hepatocellular carcinoma (HCC). However, its prognostic significance in HCC remains unclear. In the present study, we investigated the expression and significance of PCNA in HCC and then analyzed the role of PCNA in clinical outcomes. Our findings show that the expression intensity of PCNA is much higher in HCC tissues than that in paracarcinoma tissues and associated with AFP, albumin, tumor number, clinical grade, vascular invasion, and tumor-node-metastasis (TNM) stage (all p < 0.000). Kaplan-Meier analysis indicated that high PCNA expression was associated with poor disease free survival (DFS) (p < 0.000) and overall survival (OS) (p < 0.000) in a training cohort of 76 HCC patients. Multiple Cox regression analysis indicated PCNA acts as an independent predictor for DFS (p = 0.002) and OS (p = 0.004) in HCC patients. Along with pathological results, our systematic review also identified the expression of PCNA was closely associated with DFS and OS (both p < 0.000). In conclusion, this study suggested that PCNA is increased in HCC patients and is indeed a novel unfavorable biomarker for prognostic prediction for patients with this deadly disease. PMID- 26676640 TI - [Posttraumatic endophthalmitis : Complication following severe eye injury]. AB - BACKGROUND: Posttraumatic endophthalmitis is a rare but another extremely threatening complication for quality of vision, which has already been compromised by the trauma after perforating eye injuries. One of the substantial difficulties is the distinction between posttraumatic inflammation and development of a bacterial infection. METHODS: In a hospital-based study 149 consecutive cases of perforating ocular trauma with open injuries to the eye within a 5-year period were retrospectively investigated. The study included assessment of the relationship between the severity of the injury and the risk of posttraumatic endophthalmitis using the ocular trauma score (OTS), the diagnosis, the therapeutic management and the prognosis concerning visual outcome 1 year after the posttraumatic endophthalmitis. RESULTS: In this study posttraumatic endophthalmitis was observed in 8 out of 149 cases (5.4 %) after perforating ocular injuries. Severe injuries had a higher risk of this complication. In comparison to the clinical courses of non-postraumatic endophthalmitis, the visual outcome showed a tendency to be worse after an average of 18 +/- 6 months (1.25 vs 1.0 logMAR). In all of the cases the posttraumatic endophthalmitis could be successfully treated with antibiotics and surgery and the already severely limited visual function due to the injury could at least be maintained in most cases. DISCUSSION: Due to the low case numbers statistical evidence of a clear benefit of treatment by a rapidly initiated and intensive individualized surgery following trauma and a pathogen-specific and operative therapy is not possible: nevertheless, such a comprehensive therapeutic approach to posttraumatic endophthalmitis is recommended. PMID- 26676641 TI - [Retinal bleeding and venous stasis in a 10-month-old infant after a fall?]. AB - This report describes the case of a 10-month-old infant, who was delivered to our hospital by the emergency physician intubated and in an unclear unconscious state. The father reported that the child had fallen from the couch to the ground. The consulted ophthalmologist reported venous stasis in both eyes including intraretinal and preretinal bleeding in all four quadrants, a diffuse vitreous hemorrhage in the right eye and temporal retinal wrinkling in both eyes. Based on these particular clinical findings a shaken baby syndrome was suspected. This report demonstrates the importance of recognizing and correctly interpreting the typical ophthalmological signs of physical child abuse in order to detect and prevent further mistreatment of children; moreover, the increasing importance of photographic documentation and histological work-up of the findings for forensic reasons are emphasized. PMID- 26676642 TI - Base-excision repair and beyond --A short summary attributed to scientific achievements of Tomas Lindahl, Nobel Prize Laureate in Chemistry 2015. PMID- 26676644 TI - Spatial organization of cellulose microfibrils and matrix polysaccharides in primary plant cell walls as imaged by multichannel atomic force microscopy. AB - We used atomic force microscopy (AFM), complemented with electron microscopy, to characterize the nanoscale and mesoscale structure of the outer (periclinal) cell wall of onion scale epidermis - a model system for relating wall structure to cell wall mechanics. The epidermal wall contains ~100 lamellae, each ~40 nm thick, containing 3.5-nm wide cellulose microfibrils oriented in a common direction within a lamella but varying by ~30 to 90 degrees between adjacent lamellae. The wall thus has a crossed polylamellate, not helicoidal, wall structure. Montages of high-resolution AFM images of the newly deposited wall surface showed that single microfibrils merge into and out of short regions of microfibril bundles, thereby forming a reticulated network. Microfibril direction within a lamella did not change gradually or abruptly across the whole face of the cell, indicating continuity of the lamella across the outer wall. A layer of pectin at the wall surface obscured the underlying cellulose microfibrils when imaged by FESEM, but not by AFM. The AFM thus preferentially detects cellulose microfibrils by probing through the soft matrix in these hydrated walls. AFM based nanomechanical maps revealed significant heterogeneity in cell wall stiffness and adhesiveness at the nm scale. By color coding and merging these maps, the spatial distribution of soft and rigid matrix polymers could be visualized in the context of the stiffer microfibrils. Without chemical extraction and dehydration, our results provide multiscale structural details of the primary cell wall in its near-native state, with implications for microfibrils motions in different lamellae during uniaxial and biaxial extensions. PMID- 26676643 TI - Naive Induced Pluripotent Stem Cells Generated From beta-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9. AB - Conventional primed human embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit molecular and biological characteristics distinct from pluripotent stem cells in the naive state. Although naive pluripotent stem cells show much higher levels of self-renewal ability and multidifferentiation capacity, it is unknown whether naive iPSCs can be generated directly from patient somatic cells and will be superior to primed iPSCs. In the present study, we used an established 5i/L/FA system to directly reprogram fibroblasts of a patient with beta-thalassemia into transgene-free naive iPSCs with molecular signatures of ground-state pluripotency. Furthermore, these naive iPSCs can efficiently produce cross-species chimeras. Importantly, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease genome editing system, these naive iPSCs exhibit significantly improved gene-correction efficiencies compared with the corresponding primed iPSCs. Furthermore, human naive iPSCs could be directly generated from noninvasively collected urinary cells, which are easily acquired and thus represent an excellent cell resource for further clinical trials. Therefore, our findings demonstrate the feasibility and superiority of using patient-specific iPSCs in the naive state for disease modeling, gene editing, and future clinical therapy. SIGNIFICANCE: In the present study, transgene-free naive induced pluripotent stem cells (iPSCs) directly converted from the fibroblasts of a patient with beta-thalassemia in a defined culture system were generated. These naive iPSCs, which show ground-state pluripotency, exhibited significantly improved single-cell cloning ability, recovery capacity, and gene-targeting efficiency compared with conventional primed iPSCs. These results provide an improved strategy for personalized treatment of genetic diseases such as beta thalassemia. PMID- 26676645 TI - Prognostic impact of lymph node micrometastasis in oral and oropharyngeal squamous cell carcinomas. AB - BACKGROUND: The purpose of this study was to determine the role of lymph node micrometastasis in oral and oropharyngeal cancers. METHODS: We investigated the presence of micrometastases by cytokeratin immunohistochemical staining in 54 patients with node-negative oral and oropharyngeal carcinomas. RESULTS: The positive rate of cytokeratin expression was 13.0% (7 of 54 patients). The incidence of micrometastasis was significantly higher in patients with more invasive tumors (p < .001) and larger tumor size (p = .034). The 5-year disease specific (DS) survival rate significantly correlated with micrometastasis, margin involvement, and depth of invasion in the univariate analyses. Multivariate Cox regression analysis confirmed a significant association between the 5-year DS survival rate and micrometastasis (hazard ratio [HR] = 7.89; 95% confidence interval [CI] = 1.09-57.14; p = .041) and margin involvement (HR = 11.68; 95% CI = 1.22-111.75; p = .033). CONCLUSION: Micrometastasis was significantly correlated with the depth of invasion and tumor size in oral and oropharyngeal cancers. Furthermore, micrometastasis was associated with adverse outcomes. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1777-E1782, 2016. PMID- 26676646 TI - A meta-analysis of confocal laser endomicroscopy for the detection of neoplasia in patients with Barrett's esophagus. AB - BACKGROUND AND AIMS: Barrett's esophagus (BE) is considered the most important risk factor for development of esophageal adenocarcinoma. Confocal laser endomicroscopy (CLE) is a recently developed technique used to diagnose neoplasia in BE. This meta-analysis was performed to assess the accuracy of CLE for diagnosis of neoplasia in BE. METHODS: We searched EMBASE, PubMed, Cochrane Library, and Web of Science to identify relevant studies for all articles published up to June 27, 2015 in English. The quality of included studies was assessed using QUADAS-2. Per-patient and per-lesion pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (CIs) were calculated. RESULTS: In total, 14 studies were included in the final analysis, covering 789 patients with 4047 lesions. Seven studies were included in the per-patient analysis. Pooled sensitivity and specificity were 89% (95% CI: 0.82-0.94) and 83% (95% CI: 0.78-0.86), respectively. Ten studies were included in the per-lesion analysis. Compared with the PP analysis, the corresponding pooled sensitivity declined to 77% (95% CI: 0.73-0.81) and specificity increased to 89% (95% CI: 0.87-0.90). Subgroup analysis showed that probe-based CLE (pCLE) was superior to endoscope-based CLE (eCLE) in pooled specificity [91.4% (95% CI: 89.7-92.9) vs 86.1% (95% CI: 84.3 87.8)] and AUC for the sROC (0.885 vs 0.762). CONCLUSION: Confocal laser endomicroscopy is a valid method to accurately differentiate neoplasms from non neoplasms in BE. It can be applied to BE surveillance and early diagnosis of esophageal adenocarcinoma. PMID- 26676647 TI - Celiac Disease - A Case Series from North India: Correspondence. PMID- 26676648 TI - Smith-Magenis Syndrome: Face Speaks. AB - Smith-Magenis syndrome is a well delineated microdeletion syndrome with characteristic facial and behavioral phenotype. With the availability of the multi-targeted molecular cytogenetic techniques like Multiplex Ligation Probe Amplification and cytogenetic microarray, the cases are diagnosed even without clinical suspicion. Here, the authors present clinical features of nine Indian cases of Smith-Magenis syndrome. Characteristic facial phenotype including tented upper lip, broad forehead, midface hypoplasia, short philtrum and upslant of palpebral fissure is obvious in the photographs. The behavioral variations were seen in some of the cases but were not the presenting features. The characteristic facial phenotype can be an important clinical guide to the diagnosis. PMID- 26676649 TI - Celiac Disease - A Case Series from North India: Author's Reply. PMID- 26676650 TI - Non-contact Ultra-widefield Imaging in Lasered Retinopathy of Prematurity. PMID- 26676651 TI - Treatment of Phthiriasis Palpebrarum Mimicking Conjunctivitis in a Newborn. PMID- 26676652 TI - Concise Review: Balancing Stem Cell Self-Renewal and Differentiation with PLZF. AB - In recent years, the highly conserved promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16, ZNF145) has attracted attention as a multifunctional transcription factor involved in major biological processes during development. As a transcription factor, PLZF shows tight regulation in its cell-type-specific and stage-specific expression patterns. Emerging evidence shows that PLZF regulates the balance of self-renewal and differentiation in stem cells. However, the gene regulatory network of PLZF is only beginning to be understood. In this review, we discuss the diverse functions of PLZF, in particular its role in self renewal versus differentiation of stem cells. We also discuss the current state of knowledge on the gene regulatory network of PLZF, in conjunction with its upstream factors, post-translational modifications and binding cofactors for multiprotein complexes. This review aims to provide the reader with an in-depth understanding of the molecular mechanisms underlying PLZF and the potential applications in tissue regeneration. PMID- 26676653 TI - The Importance of Assessing Neural Trajectories in Pediatric Depression. PMID- 26676654 TI - ART results with frozen oocytes: data from the Italian ART registry (2005-2013). AB - PURPOSE: This study is a retrospective collection of aggregated data from all the Italian ART centers reporting to the Italian National Register from cycles started between January 2005 and December 2013. METHODS: Data from both slow freezing (SF) and vitrification (V) were assessed for the period 2007-2013, while during the years 2005-2006 cryopreservation was exclusively performed by SF. RESULTS: In the study period, a total of 2,526,024 oocytes were retrieved (from 378,543 retrievals), of which 1,346,061 (53.3 %) were inseminated in fresh cycles and 214,481 (8.5 %) were cryopreserved. Cryopreserved oocytes were used in 24,173 cycles yielding 19,453 transfer cycles (80.5 % of the thawing/warming cycles) and 3043 clinical pregnancies (15.6 % per transfer). A significant difference in implantation (8.7 vs 12.9 % OR 1.30 CI 1.20-1.40) and pregnancy rates per transfer (12.2 vs 14.9 % OR 1.34 CI 1.23-1.46) was found between SF and V. Complete outcome data was available for 2708 pregnancies (89.8 %), leading to 1882 deliveries and 2152 live births. Neonatal major congenital anomalies were 0.9 % (20/2152). CONCLUSIONS: A wide variation in pregnancy rates were found among different centers and lower rates were reported in donor cycles and in centers with more experience. PMID- 26676655 TI - [Epilepsy-associated tumors of the central nervous system: Epilepsy surgery and oncological aspects]. AB - BACKGROUND: Among the tumors associated with chronic epilepsy, dysembryoplastic neuroepithelial tumor and ganglioglioma are the most common besides angiocentric glioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma. These tumors are usually considered as being benign. OBJECTIVE: To determine the best conservative and surgical treatment of tumors associated with epilepsy. MATERIAL AND METHODS: This article presents case reports of malignant transformation of a dysembryoplastic neuroepithelial tumor and of a tumor initially diagnosed as a ganglioglioma based on magnetic resonance imaging (MRI) criteria. Description of references in the literature on epilepsy surgery and the neuro-oncology of epilepsy-associated tumors. RESULTS: In the case of the initially histopathologically diagnosed dysembryoplastic neuroepithelial tumor, a malignant transformation occurred 5 years after incomplete resection. The differentiation from a glioblastoma was possible through the analysis of the methylation profile. In another case a tumor assumed to be a ganglioglioma showed an increase in size after 6 years. Initial histopathological results revealed a glioblastoma. The analysis of the methylation profile suggested the diagnosis of an anaplastic pleomorphic xanthoastrocytoma and as a differential diagnosis an anaplastic ganglioglioma. Tumor progress correlated with the worsening of seizures. CONCLUSION: Recent studies have shown that in the treatment of predominantly benign epilepsy-associated tumors neuro-oncological aspects should also be taken into account in addition to the epileptological considerations. In the case of malignant transformation epigenetic screening (methylation profiles) can help to classify the tumor entity more precisely. PMID- 26676657 TI - Growth traits of four maternal lines of rabbits founded on different criteria: comparisons at foundation and at last periods after selection. AB - The objective was to compare growth traits in four maternal lines of rabbits (A, V, H and LP), with the aim of understanding the consequence of the different foundation and selection processes on the growth performance of the lines. The lines are currently in the 43th, 38th, 22th and 8th generations, respectively. Two comparisons were performed. One compared the values of the lines at their foundation, using the complete data set, the full pedigree and a two-trait analysis, including data on the selection criteria, litter size. The other comparisons were done during the last period when all the lines were housed together with the same feeding and management. The numbers of records were 323 208 for weaning weight, and 300 553 for slaughter weight and average daily Gain (from 46 708 l). The pedigree file included 346 638 animals. The second analysis used only the data corresponding to each period, and the analysis was conducted using a one-trait model. The model was the same as that defined for the comparisons at the foundation, but the additive effects were excluded. The H and LP lines showed highest values for all the traits compared. In the last periods, a good agreement was observed between the estimated differences, computed with the complete model and data set, or computed with an incomplete model and only data from the comparison period. At last periods, the differences were smaller than at foundation. The importance of the correlated response in growth after selection for litter size at weaning or the importance of a non-programmed intramating selection for the growth traits can explain the changes since foundation. PMID- 26676656 TI - [Interpersonal violence in the context of affective and psychotic disorders]. AB - Some mental and neurobiological disorders are associated with an increased risk for violence against others. The stigmatization of people with mental illnesses essentially emerges from a distorted perception of this condition. This review article summarizes the available literature on the determinants, prevention, therapy and tools for prediction of serious interpersonal aggression in the context of people with mental disorders. The risks for violence against other people show substantial variation between the various diagnoses. Schizophrenia and mania carry a clearly increased risk particularly at the onset of the disorder but disease-specific pharmacological therapy can reduce these risks. The highest risk factors are in particular previous violence, misuse of alcohol and drugs, male gender and young age. Probabilistic predictions of subsequent aggression against others on an individual-specific basis are only feasible in enriched populations (especially persons with mental illnesses and a previous history of assaults). Valid individual-specific predictions of future violence in the general population or on the basis of diagnoses of mental illness are, however, currently not feasible with sufficient accuracy. PMID- 26676658 TI - miR-215 functions as a tumor suppressor in epithelial ovarian cancer through regulation of the X-chromosome-linked inhibitor of apoptosis. AB - Epithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancer, which is the third most common gynaecological malignancy worldwide. Dysregulation of miRNAs is involved in the development of different types of EOC. The present study was designed to investigate the role of abnormal expression of miR-215 in the development of EOC and to elucidate the possible molecular mechanisms. mRNA expression of miR-215 was significantly decreased in EOC tissues and cell lines. Upregulation of miR-215 inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-215 increased cell proliferation, inhibited apoptosis and decreased sensitivity to chemotherapy drugs in EOC cells. In addition, the X chromosome-linked inhibitor of apoptosis (XIAP) expression was significantly increased in EOC tissues and cell lines. Downregulation of XIAP inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. Upregulation of miR-215 notably inhibited the expression of XIAP. Moreover, overexpression of XIAP significantly inhibited miR-215-exerted decrease of proliferation, increase of apoptosis and increase of sensitivity to chemotherapy drugs. In conclusion, we identified miR-215 as a potential tumor suppressor in patients with EOC downregulating expression of the oncogenic regulator XIAP. The data demonstrate that miR-215/XIAP pathway may serve as novel therapeutic targets and prognostic markers in patients with EOC. PMID- 26676659 TI - Vascular Impairment of Epineurial Arterioles of the Sciatic Nerve: Implications for Diabetic Peripheral Neuropathy. AB - This article reviews the impact of diabetes and its treatment on vascular function with a focus on the reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve. Another focus is the relationship between the dysregulation of neurovascular function and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. The etiology involves metabolic, vascular, and immunologic pathways besides neurohormonal growth factor deficiency and extracellular matrix remodeling. In the light of this complex etiology, an effective treatment for diabetic peripheral neuropathy has not yet been identified. Current opinion postulates that any effective treatment for diabetic peripheral neuropathy will require a combination of life style and therapeutic interventions. However, a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed before such a treatment strategy can be developed. After reading this review, the reader should have gained insight into the complex regulation of vascular function and blood flow to the sciatic nerve, and the impact of diabetes on numerous elements of vascular reactivity of epineurial arterioles of the sciatic nerve. PMID- 26676660 TI - Distal Sensorimotor Neuropathy: Improvements in Diagnosis. AB - Neurological complications of diabetes are common, affecting up to 50% of people with diabetes. In these patients, diabetic sensorimotor neuropathy (DSPN) is by far the most frequent complication. Detecting DSPN has traditionally been a clinical exercise that is based on signs and symptoms. However, the appearance of morphometric and neurophysiological techniques along with composite scoring systems and new screening tools has induced a paradigm change in the detection and stratification of DSPN and our understanding of its natural history and etiopathogenesis. These newer techniques have provided further evidence that changes in small nerve fiber structure and function precede large fiber changes in diabetes. Although useful, the challenge for the use of these new techniques will be their sensitivity and specificity when widely adopted and ultimately, their ability to demonstrate improvement when pathogenic mechanisms are corrected. Concurrently, we have also witnessed an emergence of simpler screening tools or methods that are mainly aimed at quicker detection of large fiber neuropathy in the outpatient setting. In this review, we have focused on techniques and tools that receive particular attention in the current literature, their use in research and potential use in the clinical environment. PMID- 26676661 TI - Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015. AB - Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities. PMID- 26676662 TI - Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions. AB - Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the gamma-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. PMID- 26676664 TI - Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis. AB - Diabetic nephropathy is the leading cause of end-stage renal disease. Patients with diabetic nephropathy have a high cardiovascular risk, comparable to patients with coronary heart disease. Accordingly, identification and management of risk factors for diabetic nephropathy as well as timely diagnosis and prompt management of the condition are of paramount importance for effective treatment. A variety of risk factors promotes the development and progression of diabetic nephropathy, including elevated glucose levels, long duration of diabetes, high blood pressure, obesity, and dyslipidemia. Most of these risk factors are modifiable by antidiabetic, antihypertensive, or lipid-lowering treatment and lifestyle changes. Others such as genetic factors or advanced age cannot be modified. Therefore, the rigorous management of the modifiable risk factors is essential for preventing and delaying the decline in renal function. Early diagnosis of diabetic nephropathy is another essential component in the management of diabetes and its complications such as nephropathy. New markers may allow earlier diagnosis of this common and serious complication, but further studies are needed to clarify their additive predictive value, and to define their cost-benefit ratio. This article reviews the most important risk factors in the development and progression of diabetic nephropathy and summarizes recent developments in the diagnosis of this disease. PMID- 26676663 TI - Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease. AB - The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID- 26676665 TI - Improvements in the Management of Diabetic Nephropathy. AB - The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy. PMID- 26676666 TI - Targeting Mitochondria and Reactive Oxygen Species-Driven Pathogenesis in Diabetic Nephropathy. AB - Diabetic kidney disease is one of the major microvascular complications of both type 1 and type 2 diabetes mellitus. Approximately 30% of patients with diabetes experience renal complications. Current clinical therapies can only mitigate the symptoms and delay the progression to end-stage renal disease, but not prevent or reverse it. Oxidative stress is an important player in the pathogenesis of diabetic nephropathy. The activity of reactive oxygen and nitrogen species (ROS/NS), which are by-products of the diabetic milieu, has been found to correlate with pathological changes observed in the diabetic kidney. However, many clinical studies have failed to establish that antioxidant therapy is renoprotective. The discovery that increased ROS/NS activity is linked to mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, cellular senescence, and cell death calls for a refined approach to antioxidant therapy. It is becoming clear that mitochondria play a key role in the generation of ROS/NS and their consequences on the cellular pathways involved in apoptotic cell death in the diabetic kidney. Oxidative stress has also been associated with necrosis via induction of mitochondrial permeability transition. This review highlights the importance of mitochondria in regulating redox balance, modulating cellular responses to oxidative stress, and influencing cell death pathways in diabetic kidney disease. ROS/NS-mediated cellular dysfunction corresponds with progressive disease in the diabetic kidney, and consequently represents an important clinical target. Based on this consideration, this review also examines current therapeutic interventions to prevent ROS/NS-derived injury in the diabetic kidney. These interventions, mainly aimed at reducing or preventing mitochondrial-generated oxidative stress, improving mitochondrial antioxidant defense, and maintaining mitochondrial integrity, may deliver alternative approaches to halt or prevent diabetic kidney disease. PMID- 26676669 TI - Simplified Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Using Ewing's Battery. AB - AIM: To find a potential simplification of the established Ewing's battery for the diagnosis of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes (T2D). METHODS: We included 152 patients (92 men) with mean age 64.51 +/- 7.85 years and median diabetes duration of 12 years. Ewing's battery was used as the gold standard for the diagnosis of CAN. Against this, we compared the results from each test and their combinations. RESULTS: The 30:15 ratio exhibited the best diagnostic performance (AUC = 0.817, 95% CI: 0.730-0.903, p < 0.001), with 96% sensitivity, 65% specificity, and 94% negative predictive value (NPV). The corresponding values for the Valsalva ratio (VR) were 62%, 92%, and 85%, respectively. The 30:15 ratio was the strongest independent predictor of neuropathy in multivariate regression analysis; low levels yielded an odds ratio (OR) of 21.14 for CAN. The rise in diastolic blood pressure and the expiration/inspiration/VR ratio (E/I/VR) were also identified as independent predictors of CAN, with 9.45 and 10.79 ORs, respectively. CONCLUSIONS: The 30:15 ratio has the best diagnostic accuracy, primarily in the exclusion of CAN, by virtue of its very high sensitivity and NPV. If this ratio is positive for CAN, the VR, the rise in diastolic blood pressure, and the E/I/VR may be useful to increase diagnostic accuracy. This procedure is a simplified diagnostic approach that merits further evaluation to enable wider screening for CAN. PMID- 26676668 TI - New Therapeutic Approaches in Diabetic Retinopathy. AB - Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID- 26676671 TI - Reaction mechanisms in ionic liquids: the kinetics and mechanism of the reaction of O,O-diethyl (2,4-dinitrophenyl) phosphate triester with secondary alicyclic amines. AB - The reactions of O,O-diethyl 2,4-dinitrophenyl phosphate triester (1) with secondary alicyclic (SA) amines in the ionic liquids [Bmim]BF4 and [Bmim]DCA were subjected to a kinetic study. Eyring plots were obtained for the title reactions in the above ionic liquids (ILs) and also in aqueous ethanol (44 wt% ethanol). Two different reaction pathways were observed in [Bmim]BF4: nucleophilic attack at the phosphoryl center, SN2(P), and at the C-1 aromatic carbon, SN(Ar), where the product distribution remained constant and independent of the amine nature. In contrast, in [Bmim]DCA only the SN2(P) pathway was found. From the kinetic analysis of the SN2(P) pathway in both ILs, curved upwards plots of kobsdvs. 1 formylpiperazine concentration were obtained. Based on the kinetic behavior, a change in the mechanism of the SN2(P) pathway is proposed for the aminolysis of 1, from a concerted process in aqueous ethanol to a stepwise mechanism, through a zwitterionic pentacoordinate intermediate, when [Bmim]BF4 and [Bmim]DCA are used as the solvents of the reaction. PMID- 26676670 TI - Axon Guidance Molecules and Neural Circuit Remodeling After Spinal Cord Injury. AB - ...once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. Santiago Ramon y Cajal Cajal's neurotropic theory postulates that the complexity of the nervous system arises from the collaboration of neurotropic signals from neuronal and non-neuronal cells and that once development has ended, a paucity of neurotropic signals means that the pathways of the central nervous system are "fixed, ended, immutable". While the capacity for regeneration and plasticity of the central nervous system may not be quite as paltry as Cajal proposed, regeneration is severely limited in scope as there is no spontaneous regeneration of long-distance projections in mammals and therefore limited opportunity for functional recovery following spinal cord injury. It is not a far stretch from Cajal to hypothesize that reappropriation of the neurotropic programs of development may be an appropriate strategy for reconstitution of injured circuits. It has become clear, however, that a significant number of the molecular cues governing circuit development become re-active after injury and many assume roles that paradoxically obstruct the functional re-wiring of severed neural connections. Therefore, the problem to address is how individual neural circuits respond to specific molecular cues following injury, and what strategies will be necessary for instigating functional repair or remodeling of the injured spinal cord. PMID- 26676672 TI - Early use of V2 receptor antagonists is associated with a shorter hospital stay and reduction in in-hospital death in patients with decompensated heart failure. AB - Tolvaptan is an oral antagonist of arginine vasopressin receptor 2 that has been approved in Japan to reduce congestive symptoms in patients with heart failure refractory to loop diuretics. However, it is unknown whether the early use of tolvaptan results in better clinical outcomes. We retrospectively analyzed 102 consecutive patients with decompensated heart failure treated with tolvaptan at our hospital. A given patient was defined as a responder when the maximum urine volume was greater than 150 % of that observed before tolvaptan use. A logistic regression analysis revealed that the early use of tolvaptan (within 3 days after admission) was an independent factor associated with tolvaptan responsiveness. There were no significant differences in the baseline clinical parameters between the early and late tolvaptan use groups. However, the early use of tolvaptan was associated with higher tolvaptan responsiveness, a shorter duration of carperitide infusion, earlier initiation of ambulatory cardiac rehabilitation, shorter hospital stay, lower rate of in-hospital death. The early use of tolvaptan was associated with a shorter hospital stay and reduced mortality in our retrospective cohort. It might therefore be beneficial to consider administering tolvaptan earlier in patients with heart failure. PMID- 26676673 TI - Effect of age on the prognostic value of left ventricular function in patients with acute coronary syndrome: A prospective registry study. AB - OBJECTIVE: This study aims to study the prognostic impact of left ventricular function on mortality and examine the effect of age on the prognostic value of left ventricular function. METHODS: We examined the myocardial ischaemia national audit project registry (2006-2010) data with a mean follow-up of 2.1 years. Left ventricular function was categorised into good (ejection fraction ?50%), moderate (ejection fraction 30-49%) and poor (ejection fraction <30%) categories. Cox proportional hazards models were constructed to examine the prognostic significance of left ventricular function in different age groups (<65, 65-74, 75 84 and ?85 years) on all-cause mortality adjusting for baseline variables. RESULTS: Out of 424,848 patients, left ventricular function data were available for 123,609. Multiple imputations were used to impute missing values of left ventricular function and the final sample for analyses was drawn from 414,305. After controlling for confounders, 339,887 participants were included in the regression models. For any age group, mortality was higher with a worsening degree of left ventricular impairment. Increased age reduced the adverse prognosis associated with reduced left ventricular function (hazard ratios of death comparing poor left ventricular function to good left ventricular function were 2.11, 95% confidence interval 1.88-2.37 for age <65 years and 1.28, 95% confidence interval 1.20-1.36 for age ?85 years). Older patients had a high mortality risk even in those with good left ventricular function. Hazard ratios of mortality for ?85 compared to <65 years (hazard ratio = 1.00) within good, moderate and poor ejection fraction groups were 5.89, 4.86 and 3.43, respectively. CONCLUSIONS: In patients with acute coronary syndrome, clinicians should interpret the prognostic value of left ventricular function taking into account the patient's age. PMID- 26676667 TI - Biomarkers in Diabetic Retinopathy. AB - There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy. PMID- 26676675 TI - Distally Based Dorsal Metatarsal Artery Perforator Flap: Vascular Study and Clinical Implications. PMID- 26676674 TI - Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. AB - Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR-29a, miR-29b and miR-29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR-29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR-29s in lung SCC and to identify miR-29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR-29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor-suppressive miR-29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR-29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR-29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease. PMID- 26676676 TI - Does an Early and Aggressive Combined Wrapping and Dangling Procedure Affect the Clinical Outcome of Lower Extremity Free Flaps?-A Randomized Controlled Prospective Study Using Microdialysis Monitoring. AB - Background The ideal starting point for flap training (FT) with the combined wrapping and dangling procedure is still a question of debate. Most units follow their own established protocols and currently evidence of flap compromise due to FT is still lacking. The aim of this study was to prove if an early and "aggressive" wrapping and dangling protocol could lead to metabolic changes, measured by microdialysis, indicating ischemia resulting in compromised flap perfusion. Methods Between 2010 and 2014, 49 patients with microvascular free flap reconstruction of the lower limb were included in this study. Patients were randomized into two groups. Group I started FT on the 7th postoperative day, and group II started on day 3. FT consisted of a combined wrapping and dangling procedure doubling its duration daily and ending at day 5. Flaps were monitored clinically and by microdialysis for ischemia-induced changes and metabolic parameters in the flap tissue in respect to different starting points of FT. Results All 49 patients in both groups were able to complete the postoperative FT without complications. Noninferiority of the early group could be proven and microdialysis results showed no differences between both groups. Conclusion We could prove by microdialysis that an early start of FT does not lead to compromised flap perfusion. Moreover, an early start of FT can lead to a reduced length of hospital stay. Furthermore, a reduced risk for deep vein thrombosis, pulmonary embolism, and pneumonia due to earlier mobilization might be an appreciated side effect. PMID- 26676677 TI - The Anatomy and Morphology of the Superficial Peroneal Nerve. AB - Background Knowledge on the anatomical and morphological characteristics of the superficial peroneal nerve is amenable to further refinement. This cadaveric study aimed to further evaluate anatomical and morphological characteristics of the superficial peroneal nerve. Methods In this study, 10 lower limbs from five fresh cadavers were dissected. The anatomical characteristics of the superficial peroneal nerve were identified. Nerve segments were submitted for histological and morphometric analyses, and nerve thicknesses and number of fascicles were assessed. Results Regarding the superficial peroneal nerve's bifurcation, 80% of the terminal branches were distal to the point of emergence from the fascia. In 90% limbs, two sensory branches were observed immediately after the distal bifurcation of the superficial peroneal nerve. The mean distance from the fibular head to the superficial peroneal nerve's emergence from the fascia was 24.6 cm and mean nerve thickness at this point was 0.3 cm. The mean distance between the lateral malleolus and the main nerve trunk at the ankle was 4.68 cm. The mean distance from the motor branch of the peroneus brevis to the lateral malleolus was 29.3 cm. Morphometric analyses revealed an average five nerve bundles at the broadest nerve diameter (2.6 mm). Conclusion The anatomical and morphometrical characteristics of the superficial peroneal nerve indicate that it may be a safe and useful donor for autologous graft treatment of peripheral nerve injuries. Our morphological study shows a median of five fascicles, and that the thickest diameter of the nerve was 2.6 mm at the emergence from the deep to the superficial compartment. PMID- 26676678 TI - The British Association of Urological Surgeons nephrectomy audit for T1 renal tumours. PMID- 26676679 TI - Doubling our precision of risk stratification in early prostate cancer: too good to be true? PMID- 26676680 TI - Salvage radical prostatectomy: a few good men. PMID- 26676681 TI - Minimally invasive surgery or nephron preservation for small renal tumours? PMID- 26676682 TI - Serum marker %[-2]proPSA and the Prostate Health Index improve diagnostic accuracy for clinically relevant prostate cancer. PMID- 26676684 TI - Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18alpha glycyrrhetinic acid inhibits human gingival fibroblast growth. AB - BACKGROUND AND PURPOSE: This investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-alpha-glycyrrhetinic acid (18alpha-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine induced gingival overgrowth. EXPERIMENTAL APPROACH: Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 MUM 18alpha-GA for 24 or 48 h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. KEY RESULTS: 18alpha-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18alpha-GA. In addition, 18alpha-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. CONCLUSIONS AND IMPLICATIONS: 18alpha-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18alpha-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth. PMID- 26676685 TI - Hemodynamic impact of abdominal aortic aneurysm stent-graft implantation-induced stenosis. AB - The current study aims to computationally evaluate the hemodynamic impact of a novel sealing mechanism employed by a recently developed endograft (Ovation TriVascular Stent-Graft System) for endovascular aneurysm repair. The exploitation of two inflatable O-rings to achieve sealing may be advantageous in terms of accommodating challenging anatomies, but comes at a price of a marked inflow stenosis. Here, four representative patient cases of inflow stenosis ranging from 30 to 80 % were analyzed. Lumen surface models were constructed from 1 month post-operative computed tomography images and then used to numerically compute the complex endograft flow field. Our results highlight coexistence of stenotic wall regions exposed to high shear rate and post-stenotic recirculation zones. These conditions may implicate platelet activation and predispose thrombus formation and thromboembolic complications. A clinically insignificant cycle averaged pressure drop along the inflow stenosis and further in the endograft main body legs was predicted (range 0.01-1.72 mmHg) which was, however, notable at peak systole (range 3.52-19.73 mmHg). Although the functional impact of the endograft stenosis at rest flow conditions may appear insignificant, increased flow rate during exercise is expected to strongly accentuate the observed effects. Pressure drop in the endograft legs was attributed to suboptimal, based on Murray's scaling law, cross-sectional area ratio between trunk and legs of the device. PMID- 26676686 TI - A review of metaphase chromosome image selection techniques for automatic karyotype generation. AB - The karyotype is analyzed to detect the genetic abnormalities. It is generated by arranging the chromosomes after extracting them from the metaphase chromosome images. The chromosomes are non-rigid bodies that contain the genetic information of an individual. The metaphase chromosome image spread contains the chromosomes, but these chromosomes are not distinct bodies; they can either be individual chromosomes or be touching one another; they may be bent or even may be overlapping and thus forming a cluster of chromosomes. The extraction of chromosomes from these touching and overlapping chromosomes is a very tedious process. The segmentation of a random metaphase chromosome image may not give us correct and accurate results. Therefore, before taking up a metaphase chromosome image for analysis, it must be analyzed for the orientation of the chromosomes it contains. The various reported methods for metaphase chromosome image selection for automatic karyotype generation are compared in this paper. After analysis, it has been concluded that each metaphase chromosome image selection method has its advantages and disadvantages. PMID- 26676687 TI - The impact of yeast fermentation on dough matrix properties. AB - BACKGROUND: Most studies on dough properties are performed on yeastless dough to exclude the complicating, time-dependent effect of yeast. Baker's yeast, however, impacts dough matrix properties during fermentation, probably through the production of primary (CO2 and ethanol) and secondary (glycerol, acetic acid and succinic acid) metabolites. The aim of this study is to obtain a better understanding of the changes in yeasted dough behavior introduced by fermentation, by investigating the impact of yeast fermentation on Farinograph dough consistency, dough spread, Kieffer rig dough extensibility and gluten agglomeration behavior in a fermented dough-batter gluten starch separation system. RESULTS: Results show that fermentation leads to a dough with less flow and lower extensibility that breaks more easily under stress and strain. The dough showed less elastic and more plastic deformation behavior. Gluten agglomerates were smaller for yeasted dough than for the unyeasted control. CONCLUSION: These changes probably have to be attributed to metabolites generated during fermentation. Indeed, organic acids and also ethanol in concentrations produced by yeast were previously shown to have similar effects in yeastless dough. These findings imply the high importance of yeast fermentation metabolites on dough matrix properties in industrial bread production. (c) 2015 Society of Chemical Industry. PMID- 26676688 TI - Tuning photoluminescence and surface properties of carbon nanodots for chemical sensing. AB - Obtaining tunable photoluminescence (PL) with improved emission properties is crucial for successfully implementing fluorescent carbon nanodots (fCDs) in all practical applications such as multicolour imaging and multiplexed detection by a single excitation wavelength. In this study, we report a facile hydrothermal approach to adjust the PL peaks of fCDs from blue, green to orange by controlling the surface passivation reaction during the synthesis. This is achieved by tuning the passivating reagents in a step-by-step manner. The as-prepared fCDs with narrow size distribution show improved PL properties with different emission wavelengths. Detailed characterization of fCDs using elemental analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy suggested that the surface chemical composition results in this tunable PL emission. Surface passivation significantly alters the surface status, resulting in fCDs with either stronger surface oxidation or N element doping that ultimately determine their PL properties. Further experiments suggested that the as-prepared orange luminescent fCDs (O-fCDs) were sensitive and specific nanosensing platforms towards Fe(3+) determination in a complex biological environment, emphasizing their potential practical applications in clinical and biological fields. PMID- 26676691 TI - PREFACE. PMID- 26676689 TI - X-linked ichthyosis and Crigler-Najjar syndrome I: Coexistence in a male patient with two copy number variable regions of 2q37.1 and Xp22.3. AB - X-linked ichthyosis (XLI) is an X-linked recessive skin disorder generally restricted to males, which arises from mutations in the steroid sulfatase (STS) gene located on Xp22.3. Crigler-Najjar syndrome (CN-I) is a rare autosomal recessive disease caused by the homozygous or compound heterozygous mutations in the UPD-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene on chromosome 2q37. A male patient was referred to the Department of Medical Genetics with of severe icterus and ichthyosis. The patient and his family members underwent genetic tests related to XLI and CN-I. Quantitative polymerase chain reaction on genomic DNA was performed to determine the gene copy number, while single nucleotide polymorphism array analysis was conducted to identify deletion mutations. Family pedigree analysis showed that the patient and his two cousins were all affected by ichthyosis, which was in accordance with the inheritance pattern of an X-linked recessive disease. In addition, the patient's serum bilirubin concentration (>340 mmol/l) was markedly greater than the normal level. The patient presented with kernicterus and phenobarbital treatment was ineffective. The clinical diagnosis of XLI was confirmed molecularly by laboratory evidence of a maternal 1.61 M deletion (including the STS gene) on ChrXp22.31. Coincidentally, the male patient was also confirmed to carry a rare maternal inherited microdeletion (374 Kb) comprising the entire UGT1A1 gene combined with a paternal UGT1A1 mutation (c.1253delT), a causative event of CN-I. To the best of our knowledge, this study reported for the first time the comorbidity of XLI and CN-I in a male patient. The results suggested that co occurrence of these two recessive diseases in a patient may be incidental. PMID- 26676690 TI - Transcriptome analysis of near-isogenic lines provides molecular insights into starch biosynthesis in maize kernel. AB - Starch is the major component in maize kernels, providing a stable carbohydrate source for humans and livestock as well as raw material for the biofuel industry. Increasing maize kernel starch content will help meet industry demands and has the potential to increase overall yields. We developed a pair of maize near isogenic lines (NILs) with different alleles for a starch quantitative trait locus on chromosome 3 (qHS3), resulting in different kernel starch content. To investigate the candidate genes for qHS3 and elucidate their effects on starch metabolism, RNA-Seq was performed for the developing kernels of the NILs at 14 and 21 d after pollination (DAP). Analysis of genomic and transcriptomic data identified 76 genes with nonsynonymous single nucleotide polymorphisms and 384 differentially expressed genes (DEGs) in the introgressed fragment, including a hexokinase gene, ZmHXK3a, which catalyzes the conversion of glucose to glucose-6 phosphate and may play a key role in starch metabolism. The expression pattern of all DEGs in starch metabolism shows that altered expression of the candidate genes for qHS3 promoted starch synthesis, with positive consequences for kernel starch content. These results expand the current understanding of starch biosynthesis and accumulation in maize kernels and provide potential candidate genes to increase starch content. PMID- 26676692 TI - Metabolic Syndrome and Lower Urinary Tract Symptoms: Epidemiological Study. AB - Increasing evidence from clinical and epidemiological studies has shown associations between lower urinary tract symptoms (LUTS) and major chronic medical diseases. Recent epidemiological studies have revealed that, to a large extent, lifestyle factors associated with metabolism, such as obesity, physical activity, blood glucose, and diet, contribute substantially to the development of these conditions. Multiple studies have demonstrated strong independent associations between LUTS and components of metabolic syndrome. Therefore, modification of lifestyle factors may lower the risk of LUTS. Prevalence of MS is age-dependent with gender differences, and LUTS have different manifestations in men and women. LUTS-associated benign prostatic hyperplasia (BPH) have multiple evidence of correlation with MS factors; however, results were inconsistent in their correlation among prostate volume and prostate-specific antigen. There is limited data on female LUTS or other diseases such as urinary incontinence or overactive bladder and MS. Further research is required to understand their connection in the pathogenesis of LUTS and to establish a more effective prevention and a therapeutic model. PMID- 26676693 TI - Association between Metabolic Syndrome and Lower Urinary Tract Symptoms: Evidences from Epidemiological Studies. AB - Metabolic syndrome (MS) and lower urinary tract symptoms (LUTS) are both highly prevalent problems of public health in the modern era. MS has been demonstrated to increase the risks for developing cardiovascular, kidney and liver diseases, and recent epidemiological evidences have indicated a possible link between MS and urological diseases, such as erectile dysfunction (ED) in men and LUTS in both sexes. The relationship between MS and LUTS was first described by Hammarsten et al. and concluded that men with MS risk factors had a larger prostate volume and a faster growth rate. Several consequent studies have also supported the association between MS and LUTS suggestive of benign prostatic hyperplasia (BPH) in men. However, studies have reported that the female lower urinary tract was affected by the components of MS as well. However, two recent surveys did not find a significant association between MS and LUTS. To date, this association remains unclear, and future longitudinal studies are needed to further clarify the controversy. PMID- 26676694 TI - Metabolic Syndrome and Nocturia. AB - Nocturia is one of the most common urological symptoms in men and women. Its prevalence is significantly related to age, but the causes of nocturia are multifactorial, such as diabetes, obesity, and other diseases and conditions. Recently, it has been reported that metabolic syndrome (MetS) is associated with lower urinary tract symptoms, including incomplete emptying, intermittency, and nocturia. We reviewed the relationship between MetS and its components and nocturia. The results from our epidemiological study indicate that nocturia can be a marker not only of MetS but also of the precursor of MetS. PMID- 26676695 TI - Detrusor Overactivity in Hyperchoelsterolemia Rats. AB - Many theories attempt to explain the complex etiology of overactive bladder syndrome (OAB), but the exact mechanisms of the pathophysiology have yet to be fully understood. Recent findings have suggested that hypercholesterolemia is related with detrusor overactivity (DO), which, in turn, is usually associated with OAB. The present report examines published studies that have associated hypercholesterolemia with DO to determine the grounds on which such studies were based. According to our analysis, OAB and DO are closely related with hypercholesterolemia. Furthermore, DO and OAB may be affected not just by a single factor like hypercholesterolemia, but rather by all components of metabolic syndrome. Several mechanisms, including autonomic overactivity, artherosclerosis, ischemic change, alteration of nitric oxide synthase (NOS)/NO system and increased Rho-kinase activity may have a role in the relationship between OAB and hypercholesterolemia. Further studies are warranted, however, to evaluate more about the pathophysiology of OAB. PMID- 26676696 TI - Effects of Chronic Hyperlipidemia on Lower Urinary Tract Function-Bladder Dysfunction in Myocardial Infarction-Prone Watanabe Heritable Hyperlipidemic Rabbits. AB - To evaluate the effects of chronic hyperlipidemia on bladder function, we examined the functional and histological changes of the bladder in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits. Two age groups of WHHL-MI rabbits (6-12 months old, young WHHL-MI rabbits; and 20-24 months old, old WHHL-MI rabbits group) and the sex- and age-matched control rabbits were prepared. Bladder functions were evaluated using frequency volume charts and cystometrograms, and functional experiments using isolated bladder specimens. Histological studies of bladder were performed with HE staining and immunohistochemical staining with mouse monoclonal S-100 protein antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. In cystometrograms, it has been demonstrated that WHHL-MI rabbits showed significantly shorter micturition interval, smaller voided volume with non voiding contractions compared to control. There was no significant difference in voiding pressure between young WHHL-MI and control rabbits. However, old WHHL-MI rabbits showed a lower voiding pressure than control rabbits. The functional experiments revealed that carbachol- and electrical field stimulation (EFS) induced contractile responses of isolated bladder strips were significantly increased in young WHHL-MI rabbits than in control rabbits. However, in the bladder strips of old WHHL-MI rabbits, decreased responses to carbachol and EFS were observed. In WHHL-MI rabbits, bladder urothelium became thinner, smooth muscle area decreased and connective tissue area increased gradually with aging. A significant decrease in S-100 protein-positive neurons, and an increased number of CGRP-positive neurons were observed in both young and old WHHL-MI rabbits. The data demonstrated that there were differences in bladder dysfunction between young and old WHHL-MI rabbits. Old WHHL-MI rabbits showed detrusor hyperactivity with impaired contraction. This study may demonstrate the developmental mechanism of bladder dysfunction in chronic hyperlipidemia. PMID- 26676697 TI - Ischemia, Hypoxia and Oxidative Stress in Bladder Outlet Obstruction and Bladder Overdistention Injury. AB - Ischemia and the accompanied hypoxia significantly impair the function of the urinary bladder, which is further damaged by ischemia/reperfusion (I/R) injury following the re-establishment of the blood supply. Current evidences have confirmed that blood flow of the bladder is decreased by bladder outlet obstruction (BOO) and acute overdistention and that functional impairment of the urinary bladder following chronic BOO and acute overdistention might partly come from tissue ischemia and ischemia/reperfusion injury. Antioxidants, free radical scavengers or substances inhibiting I/R injury may reduce bladder damages caused by BOO or overdistention. PMID- 26676698 TI - Potential Biomarkers Utilized to Define and Manage Overactive Bladder Syndrome. AB - Clinical diagnosis of overactive bladder (OAB) syndrome has great variation and usually can only be based on subjective symptoms. Measurement of urgency severity score in adjunct with voiding diary may reflect the occurrence of OAB and incontinence severity in daily life. Urodynamic study can detect detrusor overactivity (DO), but not in all OAB patients. A more objective way and less invasive tool to diagnose and assess therapeutic outcome in OAB patients is needed. Recent investigations of the potential biomarkers for OAB include urinary and serum biomarkers and bladder wall thickness. Evidence has also shown that urinary proteins, such as nerve growth factor (NGF) and prostaglandin E2 (PGE2 ) levels increase in patients with OAB, bladder outlet obstruction (BOO) and DO. Patients with OAB have significantly higher urinary NGFlevels and urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections. However, the sensitivity of single urinary protein in the diagnosis of OAB is not high and several lower urinary tract diseases may also have elevated urinary NGF levels. Searching for a group of inflammatory biomarkers by microsphere-based array in urine might be a better method in differential diagnosis of OAB from interstitial cystitis, urinary tract infection (UTI) or urolithiasis. Bladder wall thickness has been widely investigated in the diagnosis of BOO and pediatric voiding dysfunction.The role of bladder wall thickness in the diagnosis of OAB, however, has not reach a consistent conclusion. We hereby review the latest medical advances in this field. PMID- 26676699 TI - Spontaneous Contractile Activity of the Detrusor Muscle and Its Role in the Pathogenesis of Overactive Bladder Syndrome. AB - There is accumulated evidence that spontaneous contractions (SCs) in the bladder wall are associated with afferent nerve firing in the bladder. The role of the urothelium in bladder sensation might be restricted to pathological conditions, such as interstitial cystitis or chemical cystitis in which the release of urothelium-derived mediators such as adenosine triphosphate is increased. Recent publications imply that SCs in bladders with detrusor overactivity due to spinal cord injury or bladder outlet obstruction are modulated by intracellular signal transduction mechanisms such as the RhoA/Rho-kinase pathway, denervation supersensitivity to acetylcholine, changes in ion channel activity, enhanced gap junctional intercellular communication, alterations in interstitial cells of Cajal, the actions of local mediators in the detrusor and the influence of the urothelium. Spontaneous contractions and possible consequent afferent nerve firing might participate in the generation of overactive bladder syndrome. PMID- 26676700 TI - Pathophysiology of Overactive Bladder. AB - Overactive bladder syndrome (OAB), characterized by urinary frequency, nocturia and urgency with or without incontinence, is a widespread medical condition with significant impact on quality of life. Three main factors have been proposed regarding the cause of OAB: myogenic, neurogenic and urotheliogenic. Disturbance of any of the three factors or a combination of these factors can attribute to OAB. Metabolic derangement, bladder outlet obstruction and inflammation can increase the excitability of nerve, detrusor muscle and alter the sensory and barrier functions of the urothelium. The detection of proteins in the urine such as NGF, PGE2, and proinflammatory chemokines may advance our understanding of the pathophysiology of OAB and offer novel diagnostic biomarkers of OAB. PMID- 26676701 TI - Patient-reported Goal and Goal Achievement: The Most Individualized Method of Outcome Assessment in Patients with Lower Urinary Tract Symptoms. AB - Patients with lower urinary tract diseases often have a constellation of symptoms, and the degree of distress due to individual symptoms varies. In particular, some symptoms are more bothersome to patients and lead to treatment. However, traditional outcomes, such as urodynamic data, voiding diaries, and standardized patient-reported outcomes, may fail to address the individual factors. In contrast, patient-centered outcomes rely on patients to assess treatment outcomes in terms of their concerns or goals. Goal achievement is a patient-centered outcome that was pioneered in prolapse surgery. Recently, this most individualized outcome measure has been evaluated in the context of lower urinary tract symptoms (LUTS). According to the studies, most patients with LUTS have symptom-related goals. After treatment, goal achievement in patients with overactive bladder or benign prostatic obstruction was low even when there were significant improvements in symptom severity in terms of traditional outcome measures. On the other hand, most women with stress incontinence achieved their treatment goals after midurethral sling surgeries. There are ongoing efforts to develop valid and reliable methods for assessing goal achievement that can facilitate the complex rating process and have responsiveness. Goal achievement shows a limited correlation with standardized patient-reported outcomes and no significant correlation with objective outcomes. Thus, at the moment, it can be used as a complimentary outcome measure along with other traditional methods. Further research is needed to reveal the correlation between goal achievement and overall patient satisfaction and, ultimately, to determine if assessing goal achievement can enhance patient satisfaction. PMID- 26676702 TI - Outcome Measurement of Overactive Bladder. AB - Overactive bladder (OAB) is a common disease. The diagnosis of OAB is based on its symptoms without physiological markers of disease activity. Frequently used assessment methods for OAB include frequency volume chart; urodynamic studies; patient-reported outcomes questionnaires, such as the Overactive Bladder Questionnaire, King's Health Questionnaire, patient perception of bladder conditions; and OAB symptom score. The severity of OAB and degree of improvement after treatment can be obtained by comprehensive evaluation. However, a consensus of which evaluations should be used to define the severity of OAB is still lacking. We expect a proper OAB assessment with universal acceptance in the future. PMID- 26676703 TI - Cold Stress and Urinary Frequency. AB - There have been few studies regarding the onset of urinary sensations and frequent urination induced by sudden whole-body cooling. In this article, we review the relationship between cold stress and urinary frequency based mainly on our previous studies. A recent study showed that cold stress induces bladder overactivity in conscious rats, and these effects were mediated, at least in part, by alpha1A -adrenergic receptor (AR) and alpha1D -AR. Another study suggested that the resiniferatoxin-sensitive nerves present in the urinary bladder may also be involved in the regulation of detrusor activity associated with cold stress. The mammalian transient receptor potential (TRP) channel family consists of 28 channels subdivided into five different classes: TRPV (vanilloid), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), and TRPA (ankyrin). TRP channels function as multifunctional sensors at the cellular level. They can be activated by physical (voltage, heat, cold, mechanical stress) or chemical stimuli and binding of specific ligands. In 2002, it was reported that a nonselective cation channel, TRPM8, could be activated by both menthol and thermal stimuli (8-28 degrees C). We demonstrated the presence of TRPM8 in the skin from the legs and back of rats by immunofluorescence staining and that stimulation of this receptor by menthol causes urinary frequency. There have been other reports demonstrating roles of TRPM8 not related to its thermosensory function. Further studies are needed to clarify the mechanism of cold stress induced urinary frequency, and the roles of TRPM8 in the micturition control system. PMID- 26676704 TI - Phosphodiesterase Type 5 Inhibitor and Erectile Dysfunction in Lower Urinary Tract Symptoms. AB - Benign prostatic hyperplasia (BPH) is one of the most common diseases in older men and mostly induces lower urinary tract symptoms (LUTS). Multiple studies have shown that BPH inducing LUTS are intensely correlated with erectile dysfunction (ED) and that severity of LUTS was proportional to ED severity. Although a direct causal relationship has not been clarified, a tentative pathophysiology has been suggested to interpret the relationship between two disorders. Androgen plays an important role in the maintenance of the functional and structural integrity of the lower urinary tract and penis. Low testosterone, especially free testosterone, worsened detrusor overactivity and replacement of testosterone improved LUTS in the hypogonadal BPH patients. Nitric oxide synthase and nitric oxide are decreased in the transition zone of the hyperplastic prostate but phosphodiesterase types 4, 5, 11 are prominent in transition zone of hyperplastic prostate. Phosphodiesterase type 5 (PDE5) inhibitor with a long half-life could obtain the desired effect; therefore, tadalafil and undenafil frequently have been used to evaluate the effects in the two disorders. In clinical trials, tadalafil showed improvement of BPH-induced LUTS, but few of the studies showed a significant improvement on uroflowmetry. PDE5 inhibitors increase the concentration of cyclic guanosine monophosphate (cGMP) in plasma and smooth muscle, promoting erection of the penis, as well as relaxation of the bladder neck and prostate, leading to natural voiding. Sexual function and LUTS should be assessed and discussed with the patient when choosing the appropriate strategy and the patient's response to treatment should also be evaluated at the same time. PMID- 26676705 TI - Effect of the Renin-Angiotensin System on the Obstructed Bladder. AB - Bladder hypertrophy and dysfunction are well-known bladder responses to outlet obstruction (i.e. urodynamic overload). Cardiac hypertrophy and heart failure are also caused by hemodynamic overload, and many basic and clinical studies suggest that the local renin-angiotensin system (RAS) has a crucial role in load-induced cardiac pathogenesis. The similarity of the response of the heart and the bladder to overload suggests that angiotensin II (AngII) may have a similar regulatory role in pathological remodeling, such as muscle growth and collagen production of the obstructed bladder. Previous in vitro studies show that angiotensin I is converted to AngII by angiotensin converting enzyme (ACE) or chymase, which exists in the human bladder. In addition, many studies using contractile responses to AngII, autoradiography, radioreceptor assay and mRNA expression demonstrate the presence of AngII receptor in the bladder from various animals and the human. Recent evidence indicates that AngII is released from bladder smooth muscle cells (SMCs) in response to a repetitive stretch stimulus, and subsequently activates AT1 in an autocrine fashion. This AT1 activation has been shown to mediate heparin-binding epidermal growth factor-like growth factor gene expression and to increase the DNA synthesis rate of bladder SMCs. Consistent with this in vitro study, previous studies and our preliminary data suggest the usefulness of AT1 antagonists or ACE inhibitor in bladder outlet obstruction of the rabbit and rat. Taken together, the local RAS contributes to structural and functional alterations in the bladder after obstruction. PMID- 26676706 TI - Autologous Bone Marrow-Derived Cells Regenerate Urethral Sphincters. AB - Regenerative medicine based on tissue engineering and/or stem cell therapy techniques has the potential to improve irreversibly damaged tissues. Surgical injury to the lower urinary tract can occur as a result of radical prostatectomy or bladder neck surgery. Regeneration of urethral sphincters could be an effective treatment for post-surgical intrinsic sphincter deficiency (ISD) related urinary incontinence. The replacement, enhancement, and/or recovery the urethral sphincter striated and smooth muscles could increase urethral closure pressure to help patients regain continence. Stem cells from muscle-derived satellite or adipose-derived mesenchymal cells provide temporary improvement in urethral closure pressure but do not reconstruct the muscle layer structures. Our strategy to accomplish regeneration of urethral sphincters is the utilization of autologous bone marrow-derived cells. We have developed a freeze injury model of ISD in rabbits. Freezing of the urinary sphincter causes loss of the majority of striated and smooth muscle cells, and causes a significant decrease in leak point pressure. In this review, we show that the autologous bone marrow-derived cells implanted within the freeze-injured sphincters differentiate into striated or smooth muscle cells. These cells then develop to reconstitute muscle layer structures within the sphincter. Furthermore, the leak point pressure of cell implanted rabbits is significantly higher than that of cell-free injected controls. We conclude that implantation of autologous bone marrow-derived cells could be an effective treatment for human post-surgical ISD-related urinary incontinence. PMID- 26676707 TI - Management of Recurrent or Persistent Stress Urinary Incontinence after Mid urethral Sling. AB - The mid-urethral sling (MUS) procedure is the most common treatment modality for women with stress urinary incontinence (SUI). Although this procedure is highly successful, 5-20% of patients undergoing MUS experience persistent or recurrent SUI, regarded as surgical failure. However, little is known about methods to evaluate and manage patients who fail MUS procedures. The surgical options in these patients include bulking agent injection, shortening of pre-implanted tape, pubovaginal sling and repeat MUS. Of these secondary procedures, repeat MUS is the most widely studied, although this has been limited to small case series without long-term follow-up. Repeat MUS for prior MUS failure has shown relatively good success rates, ranging from 55 to 90%, with better outcomes obtained using the retropubic rather than the transobturator route. Persistent or recurrent SUI may also be successfully managed with less invasive techniques, such as tape shortening and periurethral injection of a bulking agent. Transurethral injection therapy for primary SUI has shown success rates of more than 65% at 1 year; however, these decreased significantly thereafter to around 30% at long-term follow-up. Since the optimal management of recurrent or persistent SUI after MUS has not yet been established, long-term, prospective, randomized trials are warranted. PMID- 26676708 TI - Low-Dose Anticholinergic Combination Therapy in Male Benign Prostatic Hyperplasia Patients with Overactive Bladder Symptoms. AB - Most men with lower urinary tract symptoms have both storage and voiding symptoms. Overactive bladder symptoms occur in 50-75% of men with benign prostatic obstruction. Alpha-blockers are usually the first option in medical therapy. Even though voiding symptoms are alleviated by the use of medicines or transurethral resection of the prostate, storage symptoms continue in 30-65% of patients. Combination therapy with an alpha1-receptor antagonist and an anticholinergic agent in benign prostatic hyperplasia patients with overactive bladder symptoms significantly alleviates symptoms and improves quality of life. In clinical practice, the efficacy and safety of anticholinergic combination therapy may not be comparable with well-controlled studies. Overactive bladder symptoms usually require long-term treatment, and benign prostatic hyperplasia tends to progress with time. When male LUTS patients are treated with anticholinergic combination therapy, there are still some concerns about the development of acute urinary retention, voiding difficulty, and other anticholinergic side-effects. If the drug is prescribed in a relatively low dosage, however, this approach could be appealing regarding adverse effects. There is a relatively small number of clinical reports about low-dose combination therapy, which is in its early stages. Promising results are being reported, though the level of evidence is low. We await the final results. PMID- 26676709 TI - Videourodyanamic Examination and Tension-free Vaginal Mesh/Transobturator Tape Surgery. AB - Most pelvic organ prolapse (POP) patients have lower urinary tract symptoms (LUTS) before and after POP surgery. LUTS of POP patients consist of various storage and voiding symptoms from anatomical causes. Videourodynamic examination for POP patients provides accurate information about morphological findings of the bladder and urethra, and lower urinary tract (LUT) function. The leak point pressure (LPP) measurement at cough maneuver in the standing position is important to detect urodynamic stress urinary incontinences (UDS SUI). Prolapse reduction procedure is not perfect for the detection of SUI. PMID- 26676710 TI - Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees. AB - Enteric dysbiosis is a characteristic feature of progressive human immunodeficiency virus type 1 (HIV-1) infection but has not been observed in simian immunodeficiency virus (SIVmac)-infected macaques, including in animals with end-stage disease. This has raised questions concerning the mechanisms underlying the HIV-1 associated enteropathy, with factors other than virus infection, such as lifestyle and antibiotic use, implicated as playing possible causal roles. Simian immunodeficiency virus of chimpanzees (SIVcpz) is also associated with increased mortality in wild-living communities, and like HIV-1 and SIVmac, can cause CD4+ T cell depletion and immunodeficiency in infected individuals. Given the central role of the intestinal microbiome in mammalian health, we asked whether gut microbial constituents could be identified that are indicative of SIVcpz status and/or disease progression. Here, we characterized the gut microbiome of SIVcpz-infected and -uninfected chimpanzees in Gombe National Park, Tanzania. Subjecting a small number of fecal samples (N = 9) to metagenomic (shotgun) sequencing, we found bacteria of the family Prevotellaceae to be enriched in SIVcpz-infected chimpanzees. However, 16S rRNA gene sequencing of a larger number of samples (N = 123) failed to show significant differences in both the composition and diversity (alpha and beta) of gut bacterial communities between infected (N = 24) and uninfected (N = 26) chimpanzees. Similarly, chimpanzee stool-associated circular virus (Chi-SCV) and chimpanzee adenovirus (ChAdV) identified by metagenomic sequencing were neither more prevalent nor more abundant in SIVcpz-infected individuals. However, fecal samples collected from SIVcpz-infected chimpanzees within 5 months before their AIDS-related death exhibited significant compositional changes in their gut bacteriome. These data indicate that SIVcpz-infected chimpanzees retain a stable gut microbiome throughout much of their natural infection course, with a significant destabilization of bacterial (but not viral) communities observed only in individuals with known immunodeficiency within the last several months before their death. Am. J. Primatol. 80:e22515, 2018. (c) 2015 Wiley Periodicals, Inc. PMID- 26676711 TI - Effectiveness of Patient Choice in Nonoperative vs Surgical Management of Pediatric Uncomplicated Acute Appendicitis. AB - IMPORTANCE: Current evidence suggests that nonoperative management of uncomplicated appendicitis is safe, but overall effectiveness is determined by combining medical outcomes with the patient's and family's perspective, goals, and expectations. OBJECTIVE: To determine the effectiveness of patient choice in nonoperative vs surgical management of uncomplicated acute appendicitis in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective patient choice cohort study in patients aged 7 to 17 years with acute uncomplicated appendicitis presenting at a single pediatric tertiary acute care hospital from October 1, 2012, through March 6, 2013. Participating patients and families gave informed consent and chose between nonoperative management and urgent appendectomy. INTERVENTIONS: Urgent appendectomy or nonoperative management entailing at least 24 hours of inpatient observation while receiving intravenous antibiotics and, on demonstrating improvement of symptoms, completion of 10 days of treatment with oral antibiotics. MAIN OUTCOMES AND MEASURES: The primary outcome was the 1-year success rate of nonoperative management. Successful nonoperative management was defined as not undergoing an appendectomy. Secondary outcomes included comparisons of the rates of complicated appendicitis, disability days, and health care costs between nonoperative management and surgery. RESULTS: A total of 102 patients were enrolled; 65 patients/families chose appendectomy (median age, 12 years; interquartile range [IQR], 9-13 years; 45 male [69.2%]) and 37 patients/families chose nonoperative management (median age, 11 years; IQR, 10-14 years; 24 male [64.9%]). Baseline characteristics were similar between the groups. The success rate of nonoperative management was 89.2% (95% CI, 74.6% 97.0%) at 30 days (33 of 37 children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of 37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After 1 year, children managed nonoperatively compared with the surgery group had fewer disability days (median [IQR], 8 [5-18] vs 21 [15-25] days, respectively; P < .001) and lower appendicitis-related health care costs (median [IQR], $4219 [$2514-$7795] vs $5029 [$4596-$5482], respectively; P = .01). CONCLUSIONS AND RELEVANCE: When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01718275. PMID- 26676712 TI - A Multisite-Binding Switchable Fluorescent Probe for Monitoring Mitochondrial ATP Level Fluctuation in Live Cells. AB - Adenosine triphosphate (ATP), commonly produced in mitochondria, is required by almost all the living organisms; thus fluorescent probes for monitoring mitochondrial ATP levels fluctuation are essential and highly desired. Herein, we report a multisite-binding switchable fluorescent probe, ATP-Red 1, which selectively and rapidly responds to intracellular concentrations of ATP. Live cell imaging indicated that ATP-Red 1 mainly localized to mitochondria with good biocompatibility and membrane penetration. In particular, with the help of ATP Red 1, we successfully observed not only the decreased mitochondrial ATP levels in the presence of KCN and starvation state, but also the increased mitochondrial ATP levels in the early stage of cell apoptosis. These results indicate that ATP Red 1 is a useful tool for investigating ATP-relevant biological processes. PMID- 26676713 TI - Disseminating Justified, Well-Designed, and Well-Executed Studies Despite Nonsignificant Tests. PMID- 26676715 TI - Laparoscopic alternatives to fundoplication for gastroesophageal reflux: the role of magnetic augmentation and electrical stimulation of the lower esophageal sphincter. AB - Reflux symptoms are very common, and despite modern medication they are a major cause of disease burden and loss of quality of life worldwide. Laparoscopic anti reflux surgery is the only current effective alternative but suffers from the risks of long-term side effects. Surgery also suffers variation in standards and outcomes. Magnetic augmentation and electrical stimulation of the lower esophageal sphincter represent promising innovative procedures in the field. PMID- 26676714 TI - Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis. AB - BACKGROUND AND AIM: The serotonin reuptake transporter (SERT) terminates serotonin activity by removing it from interstitial space. Downregulated colonic SERT expression has been reported in irritable bowel disease (IBS), and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission; thus, a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing. METHODS: Twenty-two ulcerative colitis (UC) patients underwent colonoscopy examinations, during which inflamed mucosa was distinguished from that undergoing healing. Healing mucosa was classified into regular and irregular vessel patterns by narrowband imaging magnifying colonoscopy. Expressions of SERT and various inflammation-related genes in biopsy samples were assessed using a polymerase chain reaction array system and real-time polymerase chain reaction. Colitis model mice were established by administration of dextran sodium sulfate or transfer of CD4(+) T cells isolated from SAMP1 mice, then time-course changes of SERT and inflammatory gene expressions were observed in colonic mucosa. RESULTS: In UC patients, SERT expression in inflamed mucosa was significantly lower than in healing mucosa. SERT expression was decreased in healing mucosa with an irregular vessel pattern with mildly increased levels of inflammatory gene expression. In mice, SERT expression was suppressed in inflamed mucosa and continuously observed with low-grade mucosal inflammation during colitis healing. CONCLUSIONS: Sserotonin reuptake transporter expression is downregulated in healing colonic mucosa of UC patients and that suppression may be dependent on the presence of remaining low-grade colonic inflammation. PMID- 26676716 TI - Diversification, evolution and methylation of short interspersed nuclear element families in sugar beet and related Amaranthaceae species. AB - Short interspersed nuclear elements (SINEs) are non-autonomous non-long terminal repeat retrotransposons which are widely distributed in eukaryotic organisms. While SINEs have been intensively studied in animals, only limited information is available about plant SINEs. We analysed 22 SINE families from seven genomes of the Amaranthaceae family and identified 34 806 SINEs, including 19 549 full length copies. With the focus on sugar beet (Beta vulgaris), we performed a comparative analysis of the diversity, genomic and chromosomal organization and the methylation of SINEs to provide a detailed insight into the evolution and age of Amaranthaceae SINEs. The lengths of consensus sequences of SINEs range from 113 nucleotides (nt) up to 224 nt. The SINEs show dispersed distribution on all chromosomes but were found with higher incidence in subterminal euchromatic chromosome regions. The methylation of SINEs is increased compared with their flanking regions, and the strongest effect is visible for cytosines in the CHH context, indicating an involvement of asymmetric methylation in the silencing of SINEs. PMID- 26676717 TI - Behavioural linear standardized scoring system of the Lidia cattle breed by testing in herd: estimation of genetic parameters. AB - Docility is very important for cattle production, and many behavioural tests to measure this trait have been developed. However, very few objective behavioural tests to measure the opposite approach 'aggressive behaviour' have been described. Therefore, the aim of this work was to validate in the Lidia cattle breed a behavioural linear standardized scoring system that measure the aggressiveness and enable genetic analysis of behavioural traits expressing fearless and fighting ability. Reproducibility and repeatability measures were calculated for the 12 linear traits of this scoring system to assess its accuracy, and ranged from 85.3 and 94.2%, and from 66.7 to 97.9%, respectively. Genetic parameters were estimated using an animal model with a Bayesian approach. A total of 1202 behavioural records were used. The pedigree matrix contained 5001 individuals. Heritability values (with standard deviations) ranged between 0.13 (0.04) (Falls of the bull) and 0.41 (0.08) (Speed of approach to horse). Genetic correlations varied from 0.01 (0.07) to 0.90 (0.13). Finally, an exploratory factor analysis using the genetic correlation matrix was calculated. Three main factors were retained to describe the traditional genetic indexes aggressiveness, strength and mobility. PMID- 26676718 TI - Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor. AB - Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. PMID- 26676719 TI - TALEN-induced disruption of Nanog expression results in reduced proliferation, invasiveness and migration, increased chemosensitivity and reversal of EMT in HepG2 cells. AB - Accumulating evidence indicates that Nanog plays a central role in modulating the biological behaviors of human hepatocellular carcinoma (HCC). However, the underlying mechanisms remain unclear. In the present study, we employed transcription activator-like effector nucleases (TALEN) to disrupt Nanog expression in HepG2 cells and obtained subcloned cells with diallelic Nanog mutations. Significantly, we found that the expression of pluripotency factors Sox2, Oct4 and Klf4, as well as expression of cancer stem cell (CSC) marker CD133, in the Nanog-targeted HepG2 cells was markedly downregulated. This finding suggests that Nanog may play an important role in maintaining the pluripotency and malignancy of HepG2 cells. We also revealed that Nanog regulated cell proliferation by modulating the expression of cyclin D1/D3/E1 and CDK2, respectively. Additionally, the disruption of Nanog resulted in the downregulation of epithelial-mesenchymal transition (EMT) regulators Snail and Twist, which contributed to the elevated level of epithelial marker E-cadherin, and to the decreased level of mesenchymal markers N-cadherin and vimentin in the HepG2 cells. In addition, the Nanog-targeted HepG2 cells exhibited reduced ability of invasion, migration and chemoresistance in vitro. In conclusion, the disruption of Nanog expression results in less proliferation, invasiveness, migration, more chemosensitivity and reversal of EMT in HepG2 cells, by which Nanog plays crucial roles in influencing the malignant phenotype of HepG2 cells. PMID- 26676720 TI - Comparison of integrated whole-body PET/MR and PET/CT: Is PET/MR alternative to PET/CT in routine clinical oncology? AB - PURPOSE: To compare the diagnostic accuracy of whole-body PET/CT and integrated PET/MR in relation to the total scan time durations. METHODS: One hundred and twenty-three (123) patients (40 males and 83 females; mean age 59.6 years; range 20-83 years) with confirmed primary cancer and clinical suspicion of metastatic disease underwent whole-body 18F-FDG-PET/CT and 18F-FDG-PET/MR. Data acquisition was done after intravenous administration of 110-301 MBq radioactivity of 18F FDG, and PET/MR data were acquired after the PET/CT data acquisition. The mean uptake times for PET/CT and PET/MR acquisition were 68.0 +/- 8.0 and 98.0 +/- 14 min, respectively. Total scan time was 20.0 and 25.0 min for whole-body PET/CT and PET/MR imaging. RESULTS: The reconstructed PET/CT and PET/MR data detected 333/355 (93.8 %) common lesions in 111/123 (90.2 %) patients. PET/CT and PET/MR alone detected 348/355 and 340/355 lesions, respectively. No significant (p = 0.08) difference was observed for the overall detection efficiency between the two techniques. On the other hand, a significant difference was observed between the two techniques for the detection of lung (p = 0.003) and cerebrospinal (p = 0.007) lesions. The 15 lesions identified by PET/CT only included 8 lung, 3 lymph nodes, 2 bone, and 1 each of peritoneal and adrenal gland lesions. On the other hand, 7 (6 brain metastatic lesions and 1 bone lesion) were identified by PET/MR only. CONCLUSION: Integrated PET/MR is a feasible whole-body imaging modality and may score better than PET/CT for the detection of brain metastases. To further prove diagnostic utility, this technique requires further clinical validation. PMID- 26676721 TI - High-density lipoprotein therapy inhibits Porphyromonas gingivalis-induced abdominal aortic aneurysm progression. AB - Clinical and experimental studies have highlighted the potential implication of periondontal bacteria contamination in the pathogenesis of abdominal aortic aneurysms (AAA). In addition to their role in reverse cholesterol transport, high density lipoproteins (HDLs) display multiple functions, including anti inflammatory and lipopolysaccharide scavenging properties. Low plasma levels of HDL-cholesterol have been reported in AAA patients. We tested the effect of a HDL therapy in Sprague-Dawley rat model of AAA, obtained by intraluminal elastase infusion followed by repeated injections of Porphyromonas gingivalis (Pg). HDLs, isolated by ultracentrifugation of plasma from healthy human volunteers, were co injected intravenously (10 mg/kg) with Pg (1.107 Colony Forming Unit) one, eight and 15 days after elastase perfusion. Rats were sacrificed one week after the last injection. Our results show that Pg injections promote the formation of a persistent neutrophil-rich thrombus associated with increased aortic diameter in this AAA model. HDLs significantly reduced the increased AAA diameter induced by Pg. Histology showed the onset of a healing process in the Pg/HDL group. HDL injections also reduced neutrophil activation in Pg-injected rats associated with decreased cytokine levels in conditioned media and plasma. Scintigraphic analysis showed an intense uptake of 99mTc-HDL by the AAA suggesting that HDLs could exert their beneficial effect by acting directly on the thrombus components. HDL supplementation may therefore constitute a new therapeutic tool for AAA treatment. PMID- 26676722 TI - An insight into the interaction of L-proline with the transition metal cations Fe(2+), Co(2+), Ni(2+): a gas phase theoretical study. AB - The interaction of Fe(2+), Co(2+), and Ni(2+) with L-proline has been studied. Three modes of interaction have been considered: salt bridged (SB), involving binding in a bi-dentate manner through the carboxylate group of L-proline, charge solvated 1 (CS1) involving carbonyl and hydroxyl oxygen, and charge solvated 2 (CS2) involving carbonyl oxygen and the lone pair of the nitrogen atom. All calculations including geometry optimization, metal ion affinities (MIAs), and frequency calculations of the binding structures of Fe(2+), Co(2+), and Ni(2+) to L-proline were calculated using the hybrid density functional theory (DFT-B3LYP) method. All three cations were found to bind preferentially in a zwitterionic (SB) coordination pattern with the metal ion affinity in the order Ni(2+) ? Co(2+) ? Fe(2+) in all binding forms. The nature of the binding interaction between metal cations and L-proline was found to be mainly electrostatic. Comparison of the infrared vibrations of the C=O, the N-H and the O-H groups of free L-proline with L-proline-M(2+) in both CS1 and CS2 complex structures indicated a considerable shift to lower frequency during complexation. In order to gain more insight into the nature of the interaction of L-proline with group VIIIB metal ions, comparison of the interaction of L-proline with other cations such as (Li(+), Na(+), K(+), Be(2+), Mg(2+), and Ca(2+)) was made. Graphical Abstract L-proline with the transition metal cations Fe(2+), Co(2+), Ni(2.) PMID- 26676723 TI - A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6 phenethylpyridin-2(2H)-ones as potency inhibitors of HIV-1 variants. AB - 3-Iodo-4-(2'-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-ones, as effective non nucleoside reverse transcriptase inhibitors, were synthesized and resolved with different configurations. Biological results revealed that the trans-racemate 2b exhibited more potent activity than the cis-isomers. Noticeably, the trans-(S,S) enantiomer 2e turned out to be significantly more potent than its counterpart enantiomer 2d against wild-type and double-mutant strains with high selectivity indexes. PMID- 26676724 TI - [Pediatric urology]. PMID- 26676725 TI - [Bladder exstrophy: Quality of primary care and long-term prognosis]. AB - BACKGROUND: It is universally agreed that successful and gentle initial bladder closure is decisive for favorable long-term outcome. Due to a number of reasons, including a lack of comparable multicenter studies, there are numerous concepts for initial exstrophy closure. DISCUSSION: Therefore, we describe our concept of delayed, staged reconstruction without osteotomy in classical bladder exstrophy, while taking into considerion the available literature on long-term follow-up as well as on own clinical and research data. CONCLUSION: Most notably there are multiple medical but also psychological advantages of a delayed procedure. Primary closure without osteotomy is feasible and has no disadvantages in the long-term follow-up when compared to the invasive procedure of osteotomy. Due to high intravesical pressure, initial bladder neck surgery might have negative effects on bladder development and on the upper urinary tract. PMID- 26676726 TI - [Pharmacological treatment of benign prostatic hyperplasia]. AB - The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment. PMID- 26676727 TI - [The GESRU Endo-Training - strategies for the optimization of endourological skills for residents]. PMID- 26676728 TI - [Vesico-ureteral reflux: Diagnosis and treatment recommendations]. AB - BACKGROUND: Vesico-ureteral reflux (VUR) is one of the most common urologic diseases in childhood. About every third child that presents with a urinary tract infection (UTI) has urinary reflux to the ureter or kidney. Demonstration of a backflow of urine into the ureters or kidneys proves vesicoureteral reflux. In unclear cases, a positioned instillation of contrast agent (PIC) cystogram might be performed and is able to prove vesico-ureteral reflux. OBJECTIVES: Since low grade VUR has a high probability of maturation and self-limitation, infants with VUR should be given prophylactic antibiotics during their first year of life, reevaluating the status of VUR after 12 months. The aim of any treatment is to prevent renal damage. THERAPY: The individual risk of renal scarring is decisive for the choice of adequate therapy. This risk is mainly dependent on reflux grade, age, and gender of the child as well as parental therapy adherence. In principle, therapeutic options include conservative as well as endoscopic or open surgical antireflux therapies. CONCLUSION: Decisions on treatment should be made individually with parents taking into account all the findings available. PMID- 26676729 TI - The Role of Auditory Itch Contagion in Psoriasis. AB - Itch and associated scratching is a common and distressing symptom of psoriasis. Here, we tested whether people with psoriasis, relative to healthy controls, show an increased vulnerability to auditory itch contagion (a deleterious influence) when presented with sounds of itch-associated actions of scratching and rubbing. We were also interested in whether manipulating the high frequency volume of these sounds alters itch perception. Results show that both groups rated scratching sounds as more itch-inducing than rubbing sounds, and the amount of induced itch increased as a function of high frequency volume. Furthermore, the influence of high frequency volume on induced itch was more pronounced in the psoriasis group, relative to controls. These findings demonstrate the role of auditory cues in eliciting sensations of itchiness in the absence of peripheral stimulation. Reducing the high frequency volume of itch-associated sounds may offer a novel approach for targeted multisensory itch interventions. PMID- 26676730 TI - 2,4-Dihydroxy and O2 Protonated Tautomers of dThd and Thd Coexist in the Gas Phase: Methylation Alters Protonation Preferences versus dUrd and Urd. AB - The gas-phase structures of protonated thymidine, [dThd + H](+), and its modified form, protonated 5-methyluridine, [Thd + H](+), are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy combined with electronic structure calculations. IRMPD action spectra are measured over the ranges extending from ~600 to 1900 cm(-1) and ~2800 to 3800 cm(-1) using the FELIX free electron laser and an optical parametric oscillator/amplifier (OPO/OPA) laser system, respectively. Comparisons between the B3LYP/6-311+G(d,p) linear IR spectra calculated for the stable low-energy conformers and the measured IRMPD spectra are used to determine the most favorable tautomeric conformations of [dThd + H](+) and [Thd + H](+) and to identify those populated in the experiments. Both B3LYP and MP2 levels of theory predict a minor 2,4-dihydroxy tautomer as the ground-state conformer of [dThd + H](+) and [Thd + H](+) indicating that the 2'-hydroxyl substituent of Thd does not exert a significant impact on the structural features. [dThd + H](+) and [Thd + H](+) share parallel IRMPD spectral profiles and yields in both the FELIX and OPO regions. Comparisons between the measured IRMPD and calculated IR spectra suggest that minor 2,4 dihydroxy tautomers and O2 protonated conformers of [dThd + H](+) and [Thd + H](+) are populated in the experiments. Comparison of this work to our previous IRMPD spectroscopy study of protonated 2'-deoxyuridine and uridine suggests that the 5-methyl substituent alters the preferences of O2 versus O4 protonation. PMID- 26676732 TI - [Rehabilitation in Vulnerable Groups]. PMID- 26676731 TI - Evaluation of a novel type of imaging probe based on a recombinant bivalent mini antibody construct for detection of CD44v6-expressing squamous cell carcinoma. AB - We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodistribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using recombinant Fab-dHLX constructs for in vivo imaging of tumor biomarkers. PMID- 26676733 TI - [Barriers for Migrants Regarding the Access to Medical Rehabilitation on Behalf of the German Pension Insurance]. AB - OBJECTIVE: To identify barriers for migrants regarding the access to medical rehabilitation on behalf of the German Pension Insurance. METHODS: Focus groups with migrants (n=5, 42 participants) and experts (n=1, 14 participants) were conducted and examined by qualitative content analysis. RESULTS: We identified 4 categories of access barriers: 1. system-related, migrant-specific, 2. person related, migrant-specific, 3. system-related, primarily not migrant-specific, and 4. person-related, primarily not migrant-specific barriers. Barriers in categories 3 and 4 are mostly class- or gender-specific. Due to associations between migration background, social status and gender roles, these barriers are often of specific importance to migrants as well. Taking such intersections of single categories of inequality (migration background, social status, gender) into account, access barriers can interact and form complexes of barriers. CONCLUSION: In order to explain and overcome the low utilization of medical rehabilitation by migrants, the interaction of migrant-, class- and gender specific barriers in the system and in persons have to be considered. PMID- 26676734 TI - [People with Intellectual and Multiple Disabilities as a Vulnerable Population Group in Health Care]. AB - AIM OF THE STUDY: This study intends to research experiences of employees of ambulatory and stationary residential facilities for people with mental and multiple disabilities and family members concerning the health care of the target group. METHODS: A qualitative research design was applied. As a data collection tool expert interviews were used. Proxy-interviews of employees of ambulatory and stationary residential facilities for people with mental and multiple disabilities and of family members were carried out. RESULTS: In total, 21 interviews could be evaluated with the software program MAXQDA. In particular, the results show that interviewees experienced or perceived a lack of individual time, prescribed measurements, conducted interventions and measurements, etc in the health care field of independent physicians. CONCLUSION: Systematic, structural, qualification-related and financial limitations impede a high-quality care for the target group. Further studies are necessary to receive differentiated knowledge about the health situation of the target group and to optimize the health care provision. PMID- 26676735 TI - [Multidrug-Resistant Organisms (MDRO) in Rehabilitation Clinics in the Rhine-Main District, Germany, 2014: Risk Analysis and Hygiene Procedures]. AB - BACKGROUND: Many regional German MDRO-networks aim to improve the medical rehabilitation of patients with methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug-resistant pathogens. In 2014, the German Commission for Hospital Hygiene and Infection Control (KRINKO) released revised recommendations for the care of patients with MRSA. In particular, for rehabilitation facilities, these recommendations stipulated a medical risk analysis to establish necessary hygiene measures, and provide specific recommendations. MATERIAL AND METHODS: Based on a large investigation carried out in 21 rehabilitation facilities covering different medical specialties, medical risk analyses according to KRINKO were performed, and the findings evaluated separately for orthopedic, cardiologic, oncologic, neurologic, or geriatric facilities, as well as for all institutions taken together. RESULTS: The overall colonization pressure, i. e. the point prevalence of MRSA and extended spectrum beta-lactamase-producing gram-negative pathogens (ESBL) among hospitalized rehabilitation patients was found to be 0.7% and 7.7%, respectively. Impairment of the intact skin (an established risk factor for persisting MRSA colonization and MRSA infection) was found in 7% of the patients, impaired mobility requiring enhanced level of care in 4.1%, and mental confusion and/or incontinence (potentially impairing the application of hygiene measures) in 11% of patients. Compared to the total study population, there was an increase in all risk factors in geriatric and neurologic rehabilitation patients: skin barrier breaches (in neurologic and in geriatric patients: 18.3 and 19.2%, respectively), impaired mobility (32.7 and 37.0%, respectively), and mental confusion/incontinence (24.5 and 28.0%, respectively). In addition, geriatric patients demonstrated an increased overall prevalence of multidrug-resistant organisms (MRSA: 9.4%; ESBL: 22.7%). DISCUSSION: Risk analysis according to KRINKO showed that in rehabilitation facilities with internal medicine or orthopedics specialties, there was a comparably lower risk for transmission, colonization, and/or infection with multidrug-resistant pathogens, as against institutions with neurologic or geriatric specialty. It appears that in the first type of rehabilitation facilities, consistently carried out basic hygiene measures are sufficient while in neurologic or geriatric rehabilitation hospitals, these measures should be supplemented with additional hygiene measures based on medical risk analysis. Furthermore, for infection control purposes in rehabilitation facilities, patient isolation will be rarely necessary or appropriate. These analyses suggest that in the future, rehabilitation programs for MRSA/ESBL colonized patients will be more successful. PMID- 26676736 TI - [Rehabilitation Application Rejected - What Happens Then?]. AB - BACKGROUND: The German statutory pension insurance (Deutsche Rentenversicherung) rejects about a third of applications for medical rehabilitation. It is assumed that the health and occupational situation of people whose applications are rejected will become unsatisfactory. So far, there are no publications investigating the group of people with rejected applications. METHOD: Of 2 075 included applicants, 345 persons were rejected. Patients whose applications were rejected were matched with those whose applications were approved (Propensity Score-Matching). At the end of the study, evaluable data sets including all 3 time points of measurement (application, 4 and 10 months thereafter) were available for 173 applicants with rejected applications and for 223 applicants approved for rehabilitation. The course of development of both groups was analysed using variance analysis with repeated measurements. The study was conducted for 27 months (January 2012-March 2014). RESULTS: At the time of application, there were no differences in health and occupational situation between the 2 groups. Also, there were no differences between groups in their utilization of outpatient therapies in the year before their application. 4 months later, a small advantage for those with an approved application was observed, and occasionally there were even significant differences. Both groups used medical and other healthcare offers comparably frequently. 10 months after application, both groups showed further improvements. There were no differences in the number of physician or non-physician patient consultations. DISCUSSION AND CONCLUSION: Our study could not confirm the assumption that the health or occupational situation of people with rejected application for rehabilitation suffers as a result of this rejection. Rather, the opposite seems to be the case. The factors that are responsible for the improvement, however, could not be identified by our study. PMID- 26676737 TI - [Are Two-Year Vocational Retraining Programs Really Better than One-Year Programs? Findings of a Propensity Score Matched Analysis]. AB - AIM OF THE STUDY: To analyze if one- and 2-year vocational retraining programs achieve similar effects on employment. METHODS: Analyses were performed with longitudinal administrative data. We included persons aged 18-59 years, who started their retraining between January and June 2005. One- and 2-year program participants were matched by propensity scores. RESULTS: The matched groups were balanced regarding all baseline scores (one-year program: n=514; 2-year program: n=514). 4 and 5 years after start of the vocational retraining program, annual income, the duration of welfare benefits and the risk of a disability pension were comparable in both groups. However, the accumulative income between 2005 and 2009 was 9 294 Euro higher (95% CI: 3 656-14 932 Euro) in one-year retraining participants. Moreover, participants of one-year programs received less welfare benefits. CONCLUSION: The development of a vocational rehabilitation strategy needs to consider the accumulative advantage of one-year programs. PMID- 26676738 TI - [Rehabilitation Goals of Patients with Coronary Artery Disease and Chronic Back Pain - An Analysis of Free Text Responses]. AB - BACKGROUND AND OBJECTIVE: Goal-setting is considered as an important step in medical rehabilitation. Regarding patient participation in the process, the possible inability of patients to develop personal goals is often discussed as a potential obstacle. This article examines whether patients have goals for medical rehabilitation and if so, which. METHODS: 189 patients with a diagnosis of coronary heart disease and 254 patients suffering from chronic back pain were surveyed in the run-up to their inpatient rehabilitation. Using a questionnaire, patients were asked to note their 3 most important rehabilitation goals. The free text data were then analyzed qualitatively and quantitatively. RESULTS: Most patients were able to express their personal rehabilitation goals before the beginning of their rehabilitation process.. Goals referring to coping with the disease were important to patients with both diagnoses. CONCLUSION: The rehabilitation goals expressed by the patients are suited for a participative goal-setting. PMID- 26676739 TI - [Limitations of Social Participation in General Population - Normative Data of the IMET based on a Population-Based Survey in Northern Germany]. AB - BACKGROUND: Medical rehabilitation in Germany is characterized by the biopsychosocial model of the ICF. Its complexity makes it less suitable for studies in rehabilitation sciences. For an implementation of the ICF, specific assessment instruments that are able to measure activity and participation efficiently in rehabilitation are needed. Instruments measuring social participation are rarely available in German language and have been employed only in a handful of empirical works. The "Index zur Messung von Einschrankungen der Teilhabe" (IMET) was developed in 2005 and measures participation of people with different chronic diseases as described in the ICF. The IMET has been applied in many studies in rehabilitation science, but as reference values were not available so far, the results could not be classified. METHOD: In a population survey, 5 004 residents in Luebeck were randomly selected by the registration office and sent a short questionnaire. The questionnaire contained questions on the overall state of health, quality of life, prevalence of chronic diseases and limitations of participation (IMET). RESULTS: The completed questionnaire was returned by 2 755 of 4 692 eligible people (58.7%). 731 residents declined participation. Therefore, the participation quota is 43.1%. The mean age of participants was 53 years (SD: 17.1), 53% were women.Limitations of participation varied according to sex and age. Men tended to be more limited in their participation. As expected, limitations in participation increased with age. Participants with a low level of education showed a significantly higher rate of participation restrictions than people with a higher level of education. The IMET correlated significantly with the health status and quality of life as well as with the prevalence of various chronic diseases. DISCUSSION: The random sample of Luebeck inhabitants comprised people between 19 and 79 years of age. The age distribution of our sample deviated from the German population with younger people being underrepresented, and older people being overrepresented. With respect to the educational level, the random sample of the Hanseatic city showed a larger proportion of people with higher education.In this population sample, there was a sex and age-related variation in restriction in participation and this correlated highly with content-related constructs. Norm values for the IMET enable classification of limitations of participation for people undergoing rehabilitation or patients suffering from chronic diseases. PMID- 26676740 TI - [Rehabilitation of Patients with Lower Limb Amputations]. PMID- 26676741 TI - [Not Available]. PMID- 26676742 TI - Ceeing compassion in care: more than 'Six C'S'? PMID- 26676743 TI - Belgian primary school children's hydration status at school and its personal determinants. AB - PURPOSE: Dehydration has been related to several health aspects, and children are especially vulnerable. Since children spend a large time at school, we aim to examine children's hydration status at school-start and its change during the school-day by objective measures. To identify subpopulations at risk, determinants of hydration were tested. METHODS: In 371 Belgian 7-13-year-old children, hydration was measured by (1) urinary osmolality at school-start and by a pooled school-day sample; (2) body water% by impedance; (3) parental reported beverage consumption; (4) urination frequency. Linear regression analyses were used to test putative predictors of hydration status: age, sex, parental education, region (Dutch-speaking versus French-speaking part of Belgium), diet quality and adiposity. RESULTS: A mean osmolality of 888 mosmol/kg was found in the school-start sample and 767 mosmol/kg in the school-day sample. This resulted in, respectively, 76 and 54 % of the children being dehydrated (>800 mosmol/kg). In 45 % of the children, the hydration level decreased over the school-day. Also the body water% as derived from bio-impedance (57 % +/-4), the reported average daily beverage intake (911 ml) and the lower urination frequency during weekdays versus weekend days confirmed the low hydration status in our school population. Boys, Walloon children and those with higher adiposity were at increased risk of low hydration level. Diet quality was not the predictor of hydration status. CONCLUSIONS: Hydration status at school appeared problematic in this population. This emphasizes the need for more resources and attention by school management and governmental organizations. Herein, especially Walloon schools and boys should be reached. PMID- 26676744 TI - Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion. AB - Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function. Here, we show that genetic knockdown of CYFIP1 in cancer cells led to the destabilization of the WASF3 complex, loss of WASF3 function, and suppressed invasion. Based on existing crystallographic data, we developed stapled peptides, referred to as WASF Helix Mimics (WAHM), that target an alpha-helical interface between WASF3 and CYFIP1. Treatment of highly invasive breast and prostate cancer cells with WAHM inhibitor peptides significantly reduced motility and invasion in vitro. Mechanistic investigations revealed that these inhibitors suppressed the interaction between Rac and the WASF3 complex, which has been shown to promote cell migration. Furthermore, peptide-mediated inhibition of WASF3 also resulted in the dysregulation of known downstream targets such as MMP-9 and KISS1. Finally, we demonstrate that this invasive phenotype is specific to WASF3 as depletion of WASF1 and WASF2, which can also bind to CYFIP1, did not affect invasion. Collectively, our findings suggest that targeting WASF3 function with WAHM peptides could represent a promising therapeutic strategy for preventing tumor invasion and metastasis. PMID- 26676745 TI - Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling. AB - Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2-D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that drug-induced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. PMID- 26676746 TI - Balancing Protein Stability and Activity in Cancer: A New Approach for Identifying Driver Mutations Affecting CBL Ubiquitin Ligase Activation. AB - Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved, depicting the protein at different stages of its activation cycle and thus providing mechanistic insight underlying how stability-activity tradeoffs in cancer-related proteins-may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity. We found that recurrent, homozygous, and leukemia-specific mutations had greater destabilizing effects on CBL states than random noncancer mutations. We further tested the ability of these computational models, assessing the changes in CBL stability and its binding to ubiquitin-conjugating enzyme E2, by performing blind CBL-mediated EGFR ubiquitination assays in cells. Experimental CBL ubiquitin ligase activity was in agreement with the predicted changes in CBL stability and, to a lesser extent, with CBL-E2 binding affinity. Two thirds of all experimentally tested mutations affected the ubiquitin ligase activity by either destabilizing CBL or disrupting CBL-E2 binding, whereas about one-third of tested mutations were found to be neutral. Collectively, our findings demonstrate that computational methods incorporating multiple protein conformations and stability and binding affinity evaluations can successfully predict the functional consequences of cancer mutations on protein activity, and provide a proof of concept for mutations in CBL. PMID- 26676747 TI - HEATR1 Negatively Regulates Akt to Help Sensitize Pancreatic Cancer Cells to Chemotherapy. AB - Elucidating mechanisms of chemoresistance is critical to improve cancer therapy, especially for the treatment of pancreatic ductal adenocarcinoma (PDAC). Genome wide association studies have suggested the less studied gene HEAT repeat containing protein 1 (HEATR1) as a possible determinant of cellular sensitivity to different chemotherapeutic drugs. In this study, we assessed this hypothesized link in PDAC, where HEATR1 expression is downregulated significantly. HEATR1 silencing in PDAC cells increased resistance to gemcitabine and other chemotherapeutics, where this effect was associated with increased AKT kinase phosphorylation at the Thr308 regulatory site. Mechanistically, HEATR1 enhanced cell responsiveness to gemcitabine by acting as a scaffold to facilitate interactions between AKT and the protein phosphatase PP2A, thereby promoting Thr308 dephosphorylation. Consistent with these findings, treatment with the AKT inhibitor triciribine sensitized HEATR1-depleted PDAC cells to gemcitabine, suggesting that this therapeutic combination may overcome gemcitabine resistance in patients with low HEATR1 expression. Clinically, we found that HEATR1 downregulation in PDAC patients was associated with increased AKT phosphorylation, poor response to tumor resection plus gemcitabine standard-of care treatment, and shorter overall survival. Collectively, our findings establish HEATR1 as a novel regulator of AKT and a candidate predictive and prognostic indicator of drug responsiveness and outcome in PDAC patients. PMID- 26676748 TI - GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. AB - The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. In this study, we generated a mAb (BCMab1) against CD44(+) human bladder cancer cells that recognizes aberrantly glycosylated integrin alpha3beta1. The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1(+)CD44(+) cell subpopulation as BCSCs with stem cell-like properties. Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1(+)CD44(+) subpopulation and was required for BCSC self-renewal. Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1(+)CD44(+) cells and correlated with clinicopathologic features of bladder cancers. Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. PMID- 26676749 TI - Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNgamma That Induce PD-L1 Expression in Head and Neck Cancer. AB - Many cancer types, including head and neck cancers (HNC), express programmed death ligand 1 (PD-L1). Interaction between PD-L1 and its receptor, programmed death 1 (PD-1), inhibits the function of activated T cells and results in an immunosuppressive microenvironment, but the stimuli that induce PD-L1 expression are not well characterized. Interferon gamma (IFNgamma) and the epidermal growth factor receptor (EGFR) utilize Janus kinase 2 (JAK2) as a common signaling node to transmit tumor cell-mediated extrinsic or intrinsic signals, respectively. In this study, we investigated the mechanism by which these factors upregulate PD-L1 expression in HNC cells in the context of JAK/STAT pathway activation, Th1 inflammation, and HPV status. We found that wild-type, overexpressed EGFR significantly correlated with JAK2 and PD-L1 expression in a large cohort of HNC specimens. Furthermore, PD-L1 expression was induced in an EGFR- and JAK2/STAT1 dependent manner, and specific JAK2 inhibition prevented PD-L1 upregulation in tumor cells and enhanced their immunogenicity. Collectively, our findings suggest a novel role for JAK2/STAT1 in EGFR-mediated immune evasion, and therapies targeting this signaling axis may be beneficial to block PD-L1 upregulation found in a large subset of HNC tumors. PMID- 26676750 TI - Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity. AB - Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials. PMID- 26676751 TI - Treatment of Triple-Negative Breast Cancer with TORC1/2 Inhibitors Sustains a Drug-Resistant and Notch-Dependent Cancer Stem Cell Population. AB - Approximately 30% of triple-negative breast cancers (TNBC) harbor molecular alterations in PI3K/mTOR signaling, but therapeutic inhibition of this pathway has not been effective. We hypothesized that intrinsic resistance to TORC1/2 inhibition is driven by cancer stem cell (CSC)-like populations that could be targeted to enhance the antitumor action of these drugs. Therefore, we investigated the molecular mechanisms by which PI3K/mTOR inhibitors affect the stem-like properties of TNBC cells. Treatment of established TNBC cell lines with a PI3K/mTOR inhibitor or a TORC1/2 inhibitor increased the expression of CSC markers and mammosphere formation. A CSC-specific PCR array revealed that inhibition of TORC1/2 increased FGF1 and Notch1 expression. Notch1 activity was also induced in TNBC cells treated with TORC1/2 inhibitors and associated with increased mitochondrial metabolism and FGFR1 signaling. Notably, genetic and pharmacologic blockade of Notch1 abrogated the increase in CSC markers, mammosphere formation, and in vivo tumor-initiating capacity induced by TORC1/2 inhibition. These results suggest that targeting the FGFR-mitochondrial metabolism-Notch1 axis prevents resistance to TORC1/2 inhibitors by eradicating drug-resistant CSCs in TNBC, and may thus represent an attractive therapeutic strategy to improve drug responsiveness and efficacy. PMID- 26676752 TI - Comprehensive Ex Vivo Transposon Mutagenesis Identifies Genes That Promote Growth Factor Independence and Leukemogenesis. AB - Aberrant signaling through cytokine receptors and their downstream signaling pathways is a major oncogenic mechanism underlying hematopoietic malignancies. To better understand how these pathways become pathologically activated and to potentially identify new drivers of hematopoietic cancers, we developed a high throughput functional screening approach using ex vivo mutagenesis with the Sleeping Beauty transposon. We analyzed over 1,100 transposon-mutagenized pools of Ba/F3 cells, an IL3-dependent pro-B-cell line, which acquired cytokine independence and tumor-forming ability. Recurrent transposon insertions could be mapped to genes in the JAK/STAT and MAPK pathways, confirming the ability of this strategy to identify known oncogenic components of cytokine signaling pathways. In addition, recurrent insertions were identified in a large set of genes that have been found to be mutated in leukemia or associated with survival, but were not previously linked to the JAK/STAT or MAPK pathways nor shown to functionally contribute to leukemogenesis. Forced expression of these novel genes resulted in IL3-independent growth in vitro and tumorigenesis in vivo, validating this mutagenesis-based approach for identifying new genes that promote cytokine signaling and leukemogenesis. Therefore, our findings provide a broadly applicable approach for classifying functionally relevant genes in diverse malignancies and offer new insights into the impact of cytokine signaling on leukemia development. PMID- 26676753 TI - miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer. AB - Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR 34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR 34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. PMID- 26676754 TI - Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function. AB - Tumor permeability is a critical determinant of drug delivery and sensitivity, but systematic methods to identify factors that perform permeability barrier functions in the tumor microenvironment are not yet available. Multicellular tumor spheroids have become tractable in vitro models to study the impact of a three-dimensional (3D) environment on cellular behavior. In this study, we characterized the spheroid-forming potential of cancer cells and correlated the resulting spheroid morphologies with genetic information to identify conserved cellular processes associated with spheroid structure. Spheroids generated from 100 different cancer cell lines were classified into four distinct groups based on morphology. In particular, round and compact spheroids exhibited highly hypoxic inner cores and permeability barriers against anticancer drugs. Through systematic and correlative analysis, we reveal JAK-STAT signaling as one of the signature pathways activated in round spheroids. Accordingly, STAT3 inhibition in spheroids generated from the established cancer cells and primary glioblastoma patient-derived cells altered the rounded morphology and increased drug sensitivity. Furthermore, combined administration of the STAT3 inhibitor and 5 fluorouracil to a mouse xenograft model markedly reduced tumor growth compared with monotherapy. Collectively, our findings demonstrate the ability to integrate 3D culture and genetic profiling to determine the factors underlying the integrity of the permeability barrier in the tumor microenvironment, and may help to identify and exploit novel mechanisms of drug resistance. PMID- 26676755 TI - Injury-Driven Stiffening of the Dermis Expedites Skin Carcinoma Progression. AB - Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin fragility disorder characterized by injury-driven blister formation, progressive soft tissue fibrosis, and a highly elevated risk of early-onset aggressive cutaneous squamous cell carcinoma (cSCC). However, the mechanisms underlying the unusually rapid progression of RDEB to cSCC are unknown. In this study, we investigated the contribution of injury-induced skin alterations to cSCC development by using a genetic model of RDEB and organotypic skin cultures. Analysis of RDEB patient samples suggested that premalignant changes to the dermal microenvironment drive tumor progression, which led us to subject a collagen VII hypomorphic mouse model of RDEB to chemical carcinogenesis. Carcinogen-treated RDEB mice developed invasive tumors phenocopying human RDEB-cSCC, whereas wild-type mice formed papillomas, indicating that the aggressiveness of RDEB-cSCC is mutation independent. The inherent structural instability of the RDEB dermis, combined with repeated injury, increased the bioavailability of TGFbeta, which promoted extracellular matrix production, cross-linking, thickening of dermal fibrils, and tissue stiffening. The biophysically altered dermis increased myofibroblast activity and integrin beta1/pFAK/pAKT mechanosignaling in tumor cells, further demonstrating that cSCC progression is governed by pre-existing injury-driven changes in the RDEB tissue microenvironment. Treatment of three-dimensional organotypic RDEB skin cultures with inhibitors of TGFbeta signaling, lysyl oxidase, or integrin beta1-mediated mechanosignaling reduced or bypassed tissue stiffness and limited tumor cell invasion. Collectively, these findings provide a new mechanism by which RDEB tissue becomes malignant and offer new druggable therapeutic targets to prevent cSCC onset. PMID- 26676756 TI - Modulation of EZH2 Expression by MEK-ERK or PI3K-AKT Signaling in Lung Cancer Is Dictated by Different KRAS Oncogene Mutations. AB - EZH2 overexpression promotes cancer by increasing histone methylation to silence tumor suppressor genes, but how EZH2 levels become elevated in cancer is not understood. In this study, we investigated the mechanisms by which EZH2 expression is regulated in non-small cell lung carcinoma cells by oncogenic KRAS. In cells harboring KRAS(G12C) and KRAS(G12D) mutations, EZH2 expression was modulated by MEK-ERK and PI3K/AKT signaling, respectively. Accordingly, MEK-ERK depletion decreased EZH2 expression in cells harboring the KRAS(G12C) mutation, whereas PI3K/AKT depletion decreased EZH2 expression, EZH2 phosphorylation, and STAT3 activity in KRAS(G12D)-mutant cell lines. Combined inhibition of EZH2 and MEK-ERK or PI3K/AKT increased the sensitivity of cells with specific KRAS mutations to MEK-ERK and PI3K/AKT-targeted therapies. Our work defines EZH2 as a downstream effector of KRAS signaling and offers a rationale for combining EZH2 inhibitory strategies with MEK-ERK- or PI3K/AKT-targeted therapies to treat lung cancer patients, as stratified into distinct treatment groups based on specific KRAS mutations. PMID- 26676757 TI - Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease. AB - Many somatic mutations have been detected in pancreatic ductal adenocarcinoma (PDAC), leading to the identification of some key drivers of disease progression, but the involvement of large genomic rearrangements has often been overlooked. In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Integration of data from MPseq, exome sequencing, and transcriptome analysis of primary PDAC cases identified limited overlap in genes affected by both rearrangements and point mutations. However, significant overlap was observed in major PDAC-associated signaling pathways, with all PDAC exhibiting reduced SMAD4 expression, reduced SMAD-dependent TGFbeta signaling, and increased WNT and Hedgehog signaling. The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression. PMID- 26676758 TI - SSBP1 Suppresses TGFbeta-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling. AB - Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Mitochondrial function is dysregulated frequently in cancer cells to allow for adaptation to a harsh tumor microenvironment. Targeting mitochondrial biogenesis and bioenergetics is, therefore, an attractive therapeutic strategy. In this study, we performed quantitative proteomic analyses in human parental and metastatic breast cancer cell lines to identify mitochondrial proteins involved in TNBC metastasis. We found that single-strand DNA-binding protein 1 (SSBP1) was downregulated in highly metastatic breast cancer cells. Moreover, SSBP1 downregulation promoted TNBC cell metastasis in vitro and in vivo. Mechanistically, SSBP1 loss decreased mitochondrial DNA copy number, thereby potentiating calcineurin-mediated mitochondrial retrograde signaling that induced c-Rel/p50 nuclear localization, activated TGFbeta promoter activity, and TGFbeta-driven epithelial-to-mesenchymal transition. Low SSBP1 expression correlated with tumor progression and poor prognosis in patients. Collectively, our findings identified SSBP1 as a novel metastasis suppressor and elucidated the mechanisms by which dysregulated mitochondrial signaling contributes to metastatic potential, providing potential new prognostic indicators for patients with TNBC. PMID- 26676759 TI - Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition in Hematologic Malignancies. AB - Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc driven B-cell lymphoma and five other hematopoietic malignancies. We determined that Myc-mediated transcriptional repression of the miR-15 and let-7 families in malignant cells was relieved upon HDACi, and Myc was required for their upregulation. The miR-15 and let-7 families then targeted and downregulated the antiapoptotic genes Bcl-2 and Bcl-xL, respectively, to induce HDACi-mediated apoptosis. Notably, Myc also transcriptionally upregulated these miRNA in untransformed cells, indicating that this Myc-induced miRNA-mediated apoptotic pathway is suppressed in malignant cells, but becomes reactivated upon HDACi. Taken together, our results reveal a previously unknown mechanism by which Myc induces apoptosis independent of the p53 pathway and as a response to HDACi in malignant hematopoietic cells. PMID- 26676760 TI - Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. AB - BACKGROUND: Postoperative delirium (POD) is common after surgery. As age is a known risk factor, the increased ageing of the population undergoing surgery emphasizes the importance of the subject. Knowledge of other potential risk factors in older patients with surgical gastrointestinal diseases is lacking. The aim here was to collate and synthesize the published literature on risk factors for delirium in this group. METHODS: Five databases were searched (MEDLINE, Web of Science, Embase, CINAHL((r)) and PSYCinfo((r)) ) between January 1987 and November 2014. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. RESULTS: Eleven studies met the inclusion criteria; they provided a total of 1427 patients (318 with delirium and 1109 without), and predominantly included patients undergoing elective colorectal surgery. The incidence of POD ranged from 8.2 to 54.4 per cent. A total of 95 risk factors were investigated, illustrating wide heterogeneity in study design. Seven statistically significant risk factors were identified in pooled analysis: old age, American Society of Anesthesiologists (ASA) physical status grade at least III, body mass index, lower serum level of albumin, intraoperative hypotension, perioperative blood transfusion and history of alcohol excess. Patients with POD had a significantly increased duration of hospital stay and a higher mortality rate compared with those without delirium. CONCLUSION: Delirium is common in older patients undergoing gastrointestinal surgery. Several risk factors were consistently associated with POD. PMID- 26676761 TI - Occurrence, prevention and remediation of toxigenic fungi and mycotoxins in silage: a review. AB - Ruminants are considered to be less sensitive towards mycotoxins than monogastric animals because rumen microbiota have mycotoxin-detoxifying capacities. Therefore the effect of mycotoxins towards ruminants has been studied to a lesser extent compared with monogastric animals. Worldwide, a high proportion of the ruminant diet consists of silages made of forage crops (i.e. all parts of the crop above the stubble are harvested). In practice, silages are often contaminated with multiple mycotoxins. Exposure to a cocktail of mycotoxins can hamper animal production and have severe health consequences. In this article the different aspects associated with mycotoxin contamination of silage are reviewed 'from seed to feed'. An overview is given on the occurrence of toxigenic fungal species and their concomitant mycotoxins in forage crops before and after ensiling. The mycotoxin load of visually non-mouldy samples and mouldy hot spots within the same silo is also compared. Subsequently, this review delves into different problem-solving strategies. A logical first step is prevention of mould growth and mycotoxin production in the field, during harvest and during ensiling. If prevention should fail, several remediation strategies are available. These are listed, mainly focusing on the possibilities of microbial degradation of mycotoxins in vivo in silage. (c) 2015 Society of Chemical Industry. PMID- 26676762 TI - Sodium formate induces autophagy and apoptosis via the JNK signaling pathway of photoreceptor cells. AB - Incidents associated with methanol intoxication resulting from the consumption of fake wine occur not infrequently worldwide. Certain individuals are made blind due to methanol poisoning. The present study aimed to investigate the effects of sodium formate exposure on photoreceptor cells (661W cells). The 661W cells were exposed to sodium formate for 6-24 h and cell viability was determined using a 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Subsequently, the 661W cells were exposed to 15 or 30 mM sodium formate for 24 h. The level of apoptosis was determined using Hoechst 33342/propidium iodide staining, visualizing the cells under a fluorescence microscope, and annexin V fluorescein isothiocyanate staining, using flow cytometric analysis. Intracellular reactive oxygen species (ROS) were measured using 2',7' dichlorofluorescein diacetate (DCFH-DA) staining, followed by flow cytometric analysis. Autophagy of the 661W cells was measured by monodansylcadaverine staining. The activation of phosphorylated c-Jun N-terminal kinase (p-JNK), B cell lymphoma (Bcl-2), Bcl-2-associated X protein, cleaved caspase-3, cleaved caspase-9 and microtubule-associated protein 1A/1B-light chain 3 (LC3) was assessed by western blotting. The effects of Z-VAD-fmk (a pan-caspase inhibitor) and SP600125 (a JNK inhibitor) on the viability of the sodium formate-induced 661W cells were determined using an MTT assay. Sodium formate treatment induced a decrease in the viability of the 661W cells in a time- and a dose-dependent manner. In addition, sodium formate at concentrations of 15 or 30 mM markedly increased the level of apoptosis and the ROS levels, as measured by DCFH-DA staining of the 661W cells. Additionally, 661W cells exposed to sodium formate for 24 h exhibited increased levels of p-JNK, Bax, cleaved caspase-3, cleaved caspase-9 and LC3II (the phosphatidylethanolamine-modified form of LC3), although the level of Bcl-2 was decreased. Furthermore, cell cytotoxicity and autophagy were induced upon treatment with sodium formate. Z-VAD-fmk and SP600125 were able to effectively circumvent the effects of sodium formate on cell viability. These results suggested that the cytotoxicity induced by sodium formate induces the activation of the JNK signaling pathway, leading to caspase-dependent apoptosis. Increased levels of autophagy were also observed during the process of 661W cell damage induced by sodium formate. PMID- 26676763 TI - A novel method for left anterior coronary artery flow velocity assessment by transthoracic echocardiography at the peak of a supine bicycle test. AB - BACKGROUND: Assessment of coronary flow is only performed during pharmacological tests. Supine bicycle tests permit the visualization of coronary flow assessments during exercise. PURPOSE: To assess the parameters of coronary flow in the left anterior descending artery (LAD) during exercise, which could be a sign of significant LAD narrowing. MATERIAL AND METHODS: A total of 253 patients were enrolled: Group 1, 186 non-selective participants before undergoing a coronary angiography; and Group 2, 67 controls without coronary artery disease (CAD). All the patients performed a supine bicycle echocardiography test. Coronary flow velocities and coronary flow velocity reserve (CFVR) were measured at the mid segment of the LAD during exercise. Patients in Group 1 underwent a coronary angiography. RESULTS: In comparison with participants without significant LAD stenosis, patients with LAD lesions had a lower DeltaV (16 +/- 21 vs. 27 +/- 20 cm/s, P < 0.04) and a lower CFVR (1.5 +/- 0.8 vs. 2.0 +/- 0.6, P < 0.004). In comparison with patients without significant proximal LAD stenosis, the patients with proximal LAD lesions had a lower flow velocity at the peak of exercise (49 +/- 32 vs. 61 +/- 19 cm/s, P < 0.02), a lower DeltaV (13 +/- 19 vs. 26 +/- 22 cm/s, P < 0.004), and a lower CFVR (1.4 +/- 0.6 vs. 1.9 +/- 0.7, P < 0.0001). In comparison with the control group, the patients with LAD stenosis had a lower flow velocity at the peak of exercise, a lower DeltaV, and a lower CFVR. CONCLUSION: Non-invasive CFVR measurement in the LAD could provide valuable additional information to a conventional echocardiography exercise test. In routine clinical practice, CFVR is sufficient for a diagnosis of severe stenosis. PMID- 26676764 TI - Does acceptance of power distance influence propensities for problematic Internet use? Evidence from a cross-cultural study. AB - INTRODUCTION: Several studies suggest that Asian countries are particularly afflicted by problematic Internet use (PIU). METHODS: The present study investigates whether individual differences in the acceptance of power distance can be linked to overuse of the Internet in Germany and in China. Power distance has been discussed as an essential dimension on which Asian and Western societies differ. In the present study, we investigate two large non-clinical samples from Germany (n = 297) and China (n = 556) to address this question. RESULTS: Both in Germany and in China, high acceptance of power distance was positively associated with PIU. These effects were more pronounced in China compared with Germany. Moreover, the observed effects were stronger in males compared with females. DISCUSSION: Clearly, these findings are just a starting point and need to be replicated in the future. Clinical populations and a further important difference variable - collectivism - also merit consideration in future work. PMID- 26676765 TI - Structure of the mouse Toll-like receptor 13 ectodomain in complex with a conserved sequence from bacterial 23S ribosomal RNA. AB - Toll-like receptor 13 (TLR13) recognizes a conserved 10-nucleotide sequence from bacterial 23S ribosomal RNA, and binding of TLR13 to the target rRNA molecule triggers immune responses. Recently, the crystal structure of the TLR13 ectodomain bound by a 13-nucleotide single-stranded RNA (ssRNA13) was determined by using the initial phases provided by a cryo-electron microscopy map of TLR13 in complex with a 25-nucleotide ssRNA (ssRNA25). This structural snapshot describes a unique method for solving the crystal structure of the TLR13-ssRNA13 complex based on medium-resolution reconstruction of TLR13-ssRNA25 cryo-electron microscopy images. PMID- 26676766 TI - The Dynamics of HPV Infection and Cervical Cancer Cells. AB - The development of cervical cells from normal cells infected by human papillomavirus into invasive cancer cells can be modeled using population dynamics of the cells and free virus. The cell populations are separated into four compartments: susceptible cells, infected cells, precancerous cells and cancer cells. The model system of differential equations also has a free virus compartment in the system, which infect normal cells. We analyze the local stability of the equilibrium points of the model and investigate the parameters, which play an important role in the progression toward invasive cancer. By simulation, we investigate the boundary between initial conditions of solutions, which tend to stable equilibrium point, representing controlled infection, and those which tend to unbounded growth of the cancer cell population. Parameters affected by drug treatment are varied, and their effect on the risk of cancer progression is explored. PMID- 26676767 TI - Mental Health Reform Will Not Reduce US Gun Violence, Experts Say. PMID- 26676768 TI - A Catalytic DNA Activated by a Specific Strain of Bacterial Pathogen. AB - Pathogenic strains of bacteria are known to cause various infectious diseases and there is a growing demand for molecular probes that can selectively recognize them. Here we report a special DNAzyme (catalytic DNA), RFD-CD1, that shows exquisite specificity for a pathogenic strain of Clostridium difficile (C. difficile). RFD-CD1 was derived by an in vitro selection approach where a random sequence DNA library was allowed to react with an unpurified molecular mixture derived from this strain of C. difficle, coupled with a subtractive selection strategy to eliminate cross-reactivities to unintended C. difficile strains and other bacteria species. RFD-CD1 is activated by a truncated version of TcdC, a transcription factor, that is unique to the targeted strain of C. difficle. Our study demonstrates for the first time that in vitro selection offers an effective approach for deriving functional nucleic acid probes that are capable of achieving strain-specific recognition of bacterial pathogens. PMID- 26676769 TI - Deletion of Murid Herpesvirus 4 ORF63 Affects the Trafficking of Incoming Capsids toward the Nucleus. AB - Gammaherpesviruses are important human and animal pathogens. Despite the fact that they display the classical architecture of herpesviruses, the function of most of their structural proteins is still poorly defined. This is especially true for tegument proteins. Interestingly, a potential role in immune evasion has recently been proposed for the tegument protein encoded by Kaposi's sarcoma associated herpesvirus open reading frame 63 (ORF63). To gain insight about the roles of ORF63 in the life cycle of a gammaherpesvirus, we generated null mutations in the ORF63 gene of murid herpesvirus 4 (MuHV-4). We showed that disruption of ORF63 was associated with a severe MuHV-4 growth deficit both in vitro and in vivo. The latter deficit was mainly associated with a defect of replication in the lung but did not affect the establishment of latency in the spleen. From a functional point of view, inhibition of caspase-1 or the inflammasome did not restore the growth of the ORF63-deficient mutant, suggesting that the observed deficit was not associated with the immune evasion mechanism identified previously. Moreover, this growth deficit was also not associated with a defect in virion egress from the infected cells. In contrast, it appeared that MuHV-4 ORF63-deficient mutants failed to address most of their capsids to the nucleus during entry into the host cell, suggesting that ORF63 plays a role in capsid movement. In the future, ORF63 could therefore be considered a target to block gammaherpesvirus infection at a very early stage of the infection. IMPORTANCE: The important diseases caused by gammaherpesviruses in human and animal populations justify a better understanding of their life cycle. In particular, the role of most of their tegument proteins is still largely unknown. In this study, we used murid herpesvirus 4, a gammaherpesvirus infecting mice, to decipher the role of the protein encoded by the viral ORF63 gene. We showed that the absence of this protein is associated with a severe growth deficit both in vitro and in vivo that was mainly due to impaired migration of viral capsids toward the nucleus during entry. Together, our results provide new insights about the life cycle of gammaherpesviruses and could allow the development of new antiviral strategies aimed at blocking gammaherpesvirus infection at the very early stages. PMID- 26676770 TI - Targeting Innate Immunity for Antiviral Therapy through Small Molecule Agonists of the RLR Pathway. AB - The cellular response to virus infection is initiated when pathogen recognition receptors (PRR) engage viral pathogen-associated molecular patterns (PAMPs). This process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory factor 3 (IRF3). IRF3 plays a critical role in antiviral immunity to drive the expression of innate immune response genes, including those encoding antiviral factors, type 1 interferon, and immune modulatory cytokines, that act in concert to restrict virus replication. Thus, small molecule agonists that can promote IRF3 activation and induce innate immune gene expression could serve as antivirals to induce tissue-wide innate immunity for effective control of virus infection. We identified small molecule compounds that activate IRF3 to differentially induce discrete subsets of antiviral genes. We tested a lead compound and derivatives for the ability to suppress infections caused by a broad range of RNA viruses. Compound administration significantly decreased the viral RNA load in cultured cells that were infected with viruses of the family Flaviviridae, including West Nile virus, dengue virus, and hepatitis C virus, as well as viruses of the families Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus), and Paramyxoviridae (respiratory syncytial virus, Nipah virus) to suppress infectious virus production. Knockdown studies mapped this response to the RIG-I-like receptor pathway. This work identifies a novel class of host-directed immune modulatory molecules that activate IRF3 to promote host antiviral responses to broadly suppress infections caused by RNA viruses of distinct genera. IMPORTANCE: Incidences of emerging and reemerging RNA viruses highlight a desperate need for broad-spectrum antiviral agents that can effectively control infections caused by viruses of distinct genera. We identified small molecule compounds that can selectively activate IRF3 for the purpose of identifying drug-like molecules that can be developed for the treatment of viral infections. Here, we report the discovery of a hydroxyquinoline family of small molecules that can activate IRF3 to promote cellular antiviral responses. These molecules can prophylactically or therapeutically control infection in cell culture by pathogenic RNA viruses, including West Nile virus, dengue virus, hepatitis C virus, influenza A virus, respiratory syncytial virus, Nipah virus, Lassa virus, and Ebola virus. Our study thus identifies a class of small molecules with a novel mechanism to enhance host immune responses for antiviral activity against a variety of RNA viruses that pose a significant health care burden and/or that are known to cause infections with high case fatality rates. PMID- 26676771 TI - Dissecting the Role of E2 Protein Domains in Alphavirus Pathogenicity. AB - Alphaviruses represent a diverse set of arboviruses, many of which are important pathogens. Chikungunya virus (CHIKV), an arthritis-inducing alphavirus, is the cause of a massive ongoing outbreak in the Caribbean and South America. In contrast to CHIKV, other related alphaviruses, such as Venezuelan equine encephalitis virus (VEEV) and Semliki Forest virus (SFV), can cause encephalitic disease. E2, the receptor binding protein, has been implicated as a determinant in cell tropism, host range, pathogenicity, and immunogenicity. Previous reports also have demonstrated that E2 contains residues important for host range expansions and monoclonal antibody binding; however, little is known about what role each protein domain (e.g., A, B, and C) of E2 plays on these factors. Therefore, we constructed chimeric cDNA clones between CHIKV and VEEV or SFV to probe the effect of each domain on pathogenicity in vitro and in vivo. CHIKV chimeras containing each of the domains of the E2 (DeltaDomA, DeltaDomB, and DeltaDomC) from SFV, but not VEEV, were successfully rescued. Interestingly, while all chimeric viruses were attenuated compared to CHIKV in mice, DeltaDomB virus showed similar rates of infection and dissemination in Aedes aegypti mosquitoes, suggesting differing roles for the E2 protein in different hosts. In contrast to CHIKV; DeltaDomB, and to a lesser extent DeltaDomA, caused neuron degeneration and demyelination in mice infected intracranially, suggesting a shift toward a phenotype similar to SFV. Thus, chimeric CHIKV/SFV provide insights on the role the alphavirus E2 protein plays on pathogenesis. IMPORTANCE: Chikungunya virus (CHIKV) has caused large outbreaks of acute and chronic arthritis throughout Africa and Southeast Asia and has now become a massive public health threat in the Americas, causing an estimated 1.2 million human cases in just over a year. No approved vaccines or antivirals exist for human use against CHIKV or any other alphavirus. Despite the threat, little is known about the role the receptor binding protein (E2) plays on disease outcome in an infected host. To study this, our laboratory generated chimeric CHIKV containing corresponding regions of the Semliki Forest virus (SFV) E2 (domains A, B, and C) substituted into the CHIKV genome. Our results demonstrate that each domain of E2 likely plays a critical, but dissimilar role in the viral life cycle. Our experiments show that manipulation of E2 domains can be useful for studies on viral pathogenesis and potentially the production of vaccines and/or antivirals. PMID- 26676772 TI - Hemagglutinin of Influenza A Virus Antagonizes Type I Interferon (IFN) Responses by Inducing Degradation of Type I IFN Receptor 1. AB - Influenza A virus (IAV) employs diverse strategies to circumvent type I interferon (IFN) responses, particularly by inhibiting the synthesis of type I IFNs. However, it is poorly understood if and how IAV regulates the type I IFN receptor (IFNAR)-mediated signaling mode. In this study, we demonstrate that IAV induces the degradation of IFNAR subunit 1 (IFNAR1) to attenuate the type I IFN induced antiviral signaling pathway. Following infection, the level of IFNAR1 protein, but not mRNA, decreased. Indeed, IFNAR1 was phosphorylated and ubiquitinated by IAV infection, which resulted in IFNAR1 elimination. The transiently overexpressed IFNAR1 displayed antiviral activity by inhibiting virus replication. Importantly, the hemagglutinin (HA) protein of IAV was proved to trigger the ubiquitination of IFNAR1, diminishing the levels of IFNAR1. Further, influenza A viral HA1 subunit, but not HA2 subunit, downregulated IFNAR1. However, viral HA-mediated degradation of IFNAR1 was not caused by the endoplasmic reticulum (ER) stress response. IAV HA robustly reduced cellular sensitivity to type I IFNs, suppressing the activation of STAT1/STAT2 and induction of IFN-stimulated antiviral proteins. Taken together, our findings suggest that IAV HA causes IFNAR1 degradation, which in turn helps the virus escape the powerful innate immune system. Thus, the research elucidated an influenza viral mechanism for eluding the IFNAR signaling pathway, which could provide new insights into the interplay between influenza virus and host innate immunity. IMPORTANCE: Influenza A virus (IAV) infection causes significant morbidity and mortality worldwide and remains a major health concern. When triggered by influenza viral infection, host cells produce type I interferon (IFN) to block viral replication. Although IAV was shown to have diverse strategies to evade this powerful, IFN-mediated antiviral response, it is not well-defined if IAV manipulates the IFN receptor-mediated signaling pathway. Here, we uncovered that influenza viral hemagglutinin (HA) protein causes the degradation of type I IFN receptor subunit 1 (IFNAR1). HA promoted phosphorylation and polyubiquitination of IFNAR1, which facilitated the degradation of this receptor. The HA-mediated elimination of IFNAR1 notably decreased the cells' sensitivities to type I IFNs, as demonstrated by the diminished expression of IFN-induced antiviral genes. This discovery could help us understand how IAV regulates the host innate immune response to create an environment optimized for viral survival in host cells. PMID- 26676773 TI - Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles. AB - Low-fidelity RNA-dependent RNA polymerases for many RNA virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. Additionally, for many RNA viruses, replication to high titers results in the production of defective interfering particles (DIs) that also attenuate infection. We hypothesized that fidelity, recombination, and DI production are tightly linked. We show that a Sindbis virus mutator replicating at a high multiplicity of infection manifests an earlier and greater accumulation of DIs than its wild-type counterpart. The isolated DIs interfere with the replication of full-length virus in a dose-dependent manner. Importantly, the ability of the mutator virus to overproduce DIs could be linked to an increased recombination frequency. These data confirm that RNA-dependent RNA polymerase fidelity and recombination are inversely correlated for this mutator. Our findings suggest that defective interference resulting from higher recombination rates may be more detrimental to RNA virus mutators than the increase in mutational burden. IMPORTANCE: Replication, adaptation, and evolution of RNA viruses rely in large part on their low-fidelity RNA-dependent RNA polymerase. Viruses artificially modified in their polymerases to decrease fidelity (mutator viruses) are attenuated in vivo, demonstrating the important role of fidelity in viral fitness. However, attenuation was attributed solely to the modification of the viral mutation rate and the accumulation of detrimental point mutations. In this work, we described an additional phenotype of mutator viruses: an increased recombination rate leading to defective interfering particle (DI) overproduction. Because DIs are known for their inhibitory effect on viral replication, our work suggests that fidelity variants may be attenuated in vivo via several mechanisms. This has important implications in the development of fidelity variants as live attenuated vaccine strains. PMID- 26676774 TI - Diverse Array of New Viral Sequences Identified in Worldwide Populations of the Asian Citrus Psyllid (Diaphorina citri) Using Viral Metagenomics. AB - The Asian citrus psyllid, Diaphorina citri, is the natural vector of the causal agent of Huanglongbing (HLB), or citrus greening disease. Together; HLB and D. citri represent a major threat to world citrus production. As there is no cure for HLB, insect vector management is considered one strategy to help control the disease, and D. citri viruses might be useful. In this study, we used a metagenomic approach to analyze viral sequences associated with the global population of D. citri. By sequencing small RNAs and the transcriptome coupled with bioinformatics analysis, we showed that the virus-like sequences of D. citri are diverse. We identified novel viral sequences belonging to the picornavirus superfamily, the Reoviridae, Parvoviridae, and Bunyaviridae families, and an unclassified positive-sense single-stranded RNA virus. Moreover, a Wolbachia prophage-related sequence was identified. This is the first comprehensive survey to assess the viral community from worldwide populations of an agricultural insect pest. Our results provide valuable information on new putative viruses, some of which may have the potential to be used as biocontrol agents. IMPORTANCE: Insects have the most species of all animals, and are hosts to, and vectors of, a great variety of known and unknown viruses. Some of these most likely have the potential to be important fundamental and/or practical resources. In this study, we used high-throughput next-generation sequencing (NGS) technology and bioinformatics analysis to identify putative viruses associated with Diaphorina citri, the Asian citrus psyllid. D. citri is the vector of the bacterium causing Huanglongbing (HLB), currently the most serious threat to citrus worldwide. Here, we report several novel viral sequences associated with D. citri. PMID- 26676775 TI - Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy. AB - In this study, we examined the peripheral blood (PB) central memory (TCM) CD4(+) T cell subsets designated peripheral T follicular helper cells (pTfh cells) and non-pTfh cells to assess HIV permissiveness and persistence. Purified pTfh and non-pTfh cells from healthy HIV-negative donors were tested for HIV permissiveness using green fluorescent protein (GFP)-expressing HIV-1NL4-3/Ba-L, followed by viral reactivation using beads coated with anti-CD3/anti-CD28 monoclonal antibodies. The role of pTfh cells in HIV persistence was analyzed in 12 chronically HIV-1 infected patients before and 48 weeks after initiation of raltegravir-containing combination antiretroviral therapy (cART). Total cellular HIV-1 DNA and episomes containing two copies of the viral long terminal repeat (2LTR circles) were analyzed in using droplet digital PCR in the purified pTfh and non-pTfh cells. Activation-inducible HIV p24 expression was determined by flow cytometry. Results indicate that pTfh cells, in particular PD1(+) pTfh cells, showed greater permissiveness for HIV infection than non-pTfh cells. At week 48 on cART, HIV DNA levels were unchanged from pre-cART levels, although a significant decrease in 2LTR circles was observed in both cell subsets. Inducible HIV p24 expression was higher in pTfh cells than in non-pTfh cells, with the highest frequencies in the PD1(+) CXCR3(-) pTfh cell subset. Frequencies of HLADR(+) CD38(+) activated CD4 T cells correlated with 2LTR circles in pTfh and non-pTfh cells at both time points and with p24(+) cells at entry. In conclusion, among CD4 TCM cells in PB of aviremic patients on cART, pTfh cells, in particular the PD1(+) CXCR3(-) subset, constitute a major HIV reservoir that is sustained by ongoing residual immune activation. The inducible HIV p24 assay is useful for monitoring HIV reservoirs in defined CD4 T cell subsets. IMPORTANCE: Identification of the type and nature of the cellular compartments of circulating HIV reservoirs is important for targeting of HIV cure strategies. In lymph nodes (LN), a subset of CD4 T cells called T follicular helper (Tfh) cells are preferentially infected by HIV. Central memory (TCM) CD4 T cells are the major cellular reservoir for HIV in peripheral blood and contain a subset of CD4 TCM cells expressing chemokine receptor CXCR5 similar in function to LN Tfh cells termed peripheral Tfh (pTfh) cells. We found that the circulating pTfh cells are highly susceptible to HIV infection and that in HIV-infected patients, HIV persists in these cells following plasma virus suppression with potent cART. These pTfh cells, which constitute a subset of TCM CD4 T cells, can be readily monitored in peripheral blood to assess HIV persistence. PMID- 26676776 TI - The Dual Nature of Nek9 in Adenovirus Replication. AB - To successfully replicate in an infected host cell, a virus must overcome sophisticated host defense mechanisms. Viruses, therefore, have evolved a multitude of devices designed to circumvent cellular defenses that would lead to abortive infection. Previous studies have identified Nek9, a cellular kinase, as a binding partner of adenovirus E1A, but the biology behind this association remains a mystery. Here we show that Nek9 is a transcriptional repressor that functions together with E1A to silence the expression of p53-inducible GADD45A gene in the infected cell. Depletion of Nek9 in infected cells reduces virus growth but unexpectedly enhances viral gene expression from the E2 transcription unit, whereas the opposite occurs when Nek9 is overexpressed. Nek9 localizes with viral replication centers, and its depletion reduces viral genome replication, while overexpression enhances viral genome numbers in infected cells. Additionally, Nek9 was found to colocalize with the viral E4 orf3 protein, a repressor of cellular stress response. Significantly, Nek9 was also shown to associate with viral and cellular promoters and appears to function as a transcriptional repressor, representing the first instance of Nek9 playing a role in gene regulation. Overall, these results highlight the complexity of virus-host interactions and identify a new role for the cellular protein Nek9 during infection, suggesting a role for Nek9 in regulating p53 target gene expression. IMPORTANCE: In the arms race that exists between a pathogen and its host, each has continually evolved mechanisms to either promote or prevent infection. In order to successfully replicate and spread, a virus must overcome every mechanism that a cell can assemble to block infection. On the other hand, to counter viral spread, cells must have multiple mechanisms to stifle viral replication. In the present study, we add to our understanding of how the human adenovirus is able to circumvent cellular roadblocks to replication. We show that the virus uses a cellular protein, Nek9, in order to block activation of p53-regulated gene GADD45A, which is an important player in stress response and p53-mediated cell cycle arrest. Importantly, our study also identifies Nek9 as a transcriptional repressor. PMID- 26676777 TI - Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques. AB - Mucosal surfaces are vulnerable to human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection and thus are key sites for eliciting vaccine-mediated protection. Vaccine protocols carried out at the Yerkes Primate Research Center utilized SIVmac239-based immunization strategies with intrarectal and intravaginal SIVsmE660 challenge of rhesus macaques. We investigated whether there were genetic signatures associated with SIVsmE660 intrarectal and intravaginal transmissions in vaccinated and unvaccinated monkeys. When transmitted/founder (T/F) envelope (Env) sequences from 49 vaccinated and 15 unvaccinated macaques were compared to each other, we were unable to identify any vaccine breakthrough signatures. In contrast, when the vaccinated and control T/F Envs were combined and compared to the challenge stock, residues at gp120 positions 23, 45, 47, and 70 (Ile-Ala-Lys-Asn [I-A-K-N]) emerged as signatures of mucosal transmission. However, T/F Envs derived from intrarectal and intravaginal infections were not different. Our data suggest that the vaginal and rectal mucosal environments both imposed a strong selection bias for SIVsmE660 variants carrying I-A-K-N that was not further enhanced by immunization. These findings, combined with the strong conservation of A-K-N in most HIV-2/SIVsmm isolates and the analogous residues in HIV-1/SIVcpz isolates, suggest that these residues confer increased transmission fitness to SIVsmE660. IMPORTANCE: Most HIV-1 infections occur across a mucosal barrier, and it is therefore important to understand why these sites are vulnerable and how to protect them with a vaccine. To gain insight into these questions, we studied rhesus macaques that were vaccinated with SIVmac239 and unvaccinated controls to determine whether the SIVsmE660 viral variants that infected these two groups were different. We did not find differences between viral variants in the absence versus presence of vaccination-induced immunity, but we did find that the SIVsmE660 viral variants that infected the monkeys, regardless of vaccination, were different from the dominant population found in the viral challenge inoculum. Our data suggest that the mucosal environments of the vagina and rectum both impose a strong selection for the SIVsmE660 variants in the challenge inoculum that are most like SIV and HIVs that circulate in nature. PMID- 26676778 TI - Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome. AB - Lytic infection by herpes simplex virus 1 (HSV-1) triggers a change in many host cell programs as the virus strives to express its own genes and replicate. Part of this process is repression of host cell transcription by RNA polymerase II (Pol II), which also transcribes the viral genome. Here, we describe a global characterization of Pol II occupancy on the viral and host genomes in response to HSV-1 infection using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). The data reveal near-complete loss of Pol II occupancy throughout host cell mRNA genes, in both their bodies and promoter-proximal regions. Increases in Pol II occupancy of host cell genes, which would be consistent with robust transcriptional activation, were not observed. HSV-1 infection induced a more potent and widespread repression of Pol II occupancy than did heat shock, another cellular stress that widely represses transcription. Concomitant with the loss of host genome Pol II occupancy, we observed Pol II covering the HSV-1 genome, reflecting a high level of viral gene transcription. Interestingly, the positions of the peaks of Pol II occupancy at HSV-1 and host cell promoters were different. IMPORTANCE: We investigated the effect of herpes simplex virus 1 (HSV 1) infection on transcription of host cell and viral genes by RNA polymerase II (Pol II). The approach we used was to determine how levels of genome-bound Pol II changed after HSV-1 infection. We found that HSV-1 caused a profound loss of Pol II occupancy across the host cell genome. Increases in Pol II occupancy were not observed, showing that no host genes were activated after infection. In contrast, Pol II occupied the entire HSV-1 genome. Moreover, the pattern of Pol II at HSV-1 genes differed from that on host cell genes, suggesting a unique mode of viral gene transcription. These studies provide new insight into how HSV-1 causes changes in the cellular program of gene expression and how the virus coopts host Pol II for its own use. PMID- 26676779 TI - Membrane Binding of the Rous Sarcoma Virus Gag Protein Is Cooperative and Dependent on the Spacer Peptide Assembly Domain. AB - The principles underlying membrane binding and assembly of retroviral Gag proteins into a lattice are understood. However, little is known about how these processes are related. Using purified Rous sarcoma virus Gag and Gag truncations, we studied the interrelation of Gag-Gag interaction and Gag-membrane interaction. Both by liposome binding and by surface plasmon resonance on a supported bilayer, Gag bound to membranes much more tightly than did matrix (MA), the isolated membrane binding domain. In principle, this difference could be explained either by protein-protein interactions leading to cooperativity in membrane binding or by the simultaneous interaction of the N-terminal MA and the C-terminal nucleocapsid (NC) of Gag with the bilayer, since both are highly basic. However, we found that NC was not required for strong membrane binding. Instead, the spacer peptide assembly domain (SPA), a putative 24-residue helical sequence comprising the 12-residue SP segment of Gag and overlapping the capsid (CA) C terminus and the NC N terminus, was required. SPA is known to be critical for proper assembly of the immature Gag lattice. A single amino acid mutation in SPA that abrogates assembly in vitro dramatically reduced binding of Gag to liposomes. In vivo, plasma membrane localization was dependent on SPA. Disulfide cross-linking based on ectopic Cys residues showed that the contacts between Gag proteins on the membrane are similar to the known contacts in virus-like particles. Taken together, we interpret these results to mean that Gag membrane interaction is cooperative in that it depends on the ability of Gag to multimerize. IMPORTANCE: The retroviral structural protein Gag has three major domains. The N-terminal MA domain interacts directly with the plasma membrane (PM) of cells. The central CA domain, together with immediately adjoining sequences, facilitates the assembly of thousands of Gag molecules into a lattice. The C-terminal NC domain interacts with the genome, resulting in packaging of viral RNA. For assembly in vitro with purified Gag, in the absence of membranes, binding of NC to nucleic acid somehow facilitates further Gag-Gag interactions that lead to formation of the Gag lattice. The contributions of MA-mediated membrane binding to virus particle assembly are not well understood. Here, we report that in the absence of nucleic acid, membranes provide a platform that facilitates Gag-Gag interactions. This study demonstrates that the binding of Gag, but not of MA, to membranes is cooperative and identifies SPA as a major factor that controls this cooperativity. PMID- 26676780 TI - Pharmacologic Inhibition of Nedd8 Activation Enzyme Exposes CD4-Induced Epitopes within Env on Cells Expressing HIV-1. AB - HIV-1 Vpu decreases the exposure of epitopes within the viral envelope glycoprotein (Env) on the surface of infected cells by downregulating both BST2 and CD4. To test the hypothesis that inhibiting Vpu activity would increase the exposure of these epitopes and sensitize infected cells to antibody-dependent cellular cytotoxicity (ADCC), we treated cells with the Nedd8 activation enzyme (NAE) inhibitor MLN4924, which inhibits the cullin1-based ubiquitin ligase complex coopted by Vpu to degrade cellular targets. Treatment of HeLa cells with MLN4924 or expression of a dominant negative mutant of cullin1 inhibited the Vpu mediated downregulation of CD4 but not the downregulation of BST2. NAE inhibition also increased the surface exposure of CD4-induced epitopes within Env on HEK293 cells containing an inducible HIV genome, on infected CEM T cells, and on infected primary T cells. In contrast, the Vpu-mediated downregulation of BST2 was substantially inhibited by MLN4924 only when T cells were treated with alpha interferon (IFN-alpha) to induce high levels of BST2 expression. As reported previously, the absence of vpu or nef and even more so the combined absence of these two genes sensitized infected cells to ADCC. However, NAE inhibition affected ADCC minimally. Paradoxically, even in infected, IFN-treated cells in which NAE inhibition substantially rescued the surface level of BST2, the surface level of Env detected with an antibody recognizing a CD4-independent epitope (2G12) was minimally increased. Mutation of the C-terminal Vpu residue W76, which supports the ability of Vpu to stimulate virion release by displacing BST2 from assembly sites on the plasma membrane by a cullin1-independent mechanism, increased the exposure of Env detected by 2G12 on infected T cells. Thus, inhibiting the displacement function of Vpu together with its ability to degrade CD4 and BST2 may be required to sensitize infected cells to ADCC. IMPORTANCE: Pathogenic viruses encode gene products that enable evasion of host immune surveillance mechanisms. One such mechanism is antibody-dependent cellular cytotoxicity (ADCC), whereby host antibodies bind envelope glycoproteins of the virus that are inserted into the cellular membrane and direct the destruction of infected cells. Targeting pharmacologically the activity of HIV-1 Vpu, which contributes to evasion of ADCC, could potentially sensitize infected cells to this immune surveillance mechanism, an outcome that would have therapeutic implications with respect to the goal of curing HIV-1 infection. The Nedd8 activation enzyme inhibitor MLN4924 blocks the activity of the host ubiquitin ligase that Vpu coopts to direct the degradation of CD4 and BST2. We observed that while MLN4924 partially reverses the activity of Vpu and could become part of a therapeutic approach by virtue of CD4-induced epitope exposure, sufficient Vpu activity as an antagonist of BST2 persists despite this drug to allow escape from ADCC. PMID- 26676781 TI - Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency. AB - Ebola virus (EBOV) is an RNA virus that can cause hemorrhagic fever with high fatality rates, and there are no approved vaccines or therapies. Typically, RNA viruses have high spontaneous mutation rates, which permit rapid adaptation to selection pressures and have other important biological consequences. However, it is unknown if filoviruses exhibit high mutation frequencies. Ultradeep sequencing and a recombinant EBOV that carries the gene encoding green fluorescent protein were used to determine the spontaneous mutation frequency of EBOV. The effects of the guanosine analogue ribavirin during EBOV infections were also assessed. Ultradeep sequencing revealed that the mutation frequency for EBOV was high and similar to those of other RNA viruses. Interestingly, significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. In vitro, the presence of ribavirin increased the error rate, and the 50% inhibitory concentration (IC50) was 27 MUM. In a mouse model of ribavirin therapy given pre EBOV exposure, ribavirin treatment corresponded with a significant delay in time to death and up to 75% survival. In mouse and monkey models of therapy given post EBOV exposure, ribavirin treatment also delayed the time to death and increased survival. These results demonstrate that EBOV has a spontaneous mutation frequency similar to those of other RNA viruses. These data also suggest a potential for therapeutic use of ribavirin for human EBOV infections. IMPORTANCE: Ebola virus (EBOV) causes a severe hemorrhagic disease with high case fatality rates; there are no approved vaccines or therapies. We determined the spontaneous mutation frequency of EBOV, which is relevant to understanding the potential for the virus to adapt. The frequency was similar to those of other RNA viruses. Significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. Ribavirin is a viral mutagen approved for treatment of several virus infections; it is also cheap and readily available. In cell culture, we showed that ribavirin was effective at reducing production of infectious EBOV. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment delayed the time to death and increased survival. These data provide a better understanding of EBOV spontaneous mutation and suggest that ribavirin may have great value in the context of human disease. PMID- 26676782 TI - TRIM5alpha-Mediated Ubiquitin Chain Conjugation Is Required for Inhibition of HIV 1 Reverse Transcription and Capsid Destabilization. AB - Rhesus macaque TRIM5alpha (rhTRIM5alpha) is a retroviral restriction factor that inhibits HIV-1 infection. Previous studies have revealed that TRIM5alpha restriction occurs via a two-step process. The first step is restriction factor binding, which is sufficient to inhibit infection. The second step, which is sensitive to proteasome inhibition, prevents the accumulation of reverse transcription products in the target cell. However, because of the pleotropic effects of proteasome inhibitors, the molecular mechanisms underlying the individual steps in the restriction process have remained poorly understood. In this study, we have fused the small catalytic domain of herpes simplex virus UL36 deubiquitinase (DUb) to the N-terminal RING domain of rhTRIM5alpha, which results in a ubiquitination-resistant protein. Cell lines stably expressing this fusion protein inhibited HIV-1 infection to the same degree as a control fusion to a catalytically inactive DUb. However, reverse transcription products were substantially increased in the DUb-TRIM5alpha fusion relative to the catalytically inactive control or the wild-type (WT) TRIM5alpha. Similarly, expression of DUb-rhTRIM5alpha resulted in the accumulation of viral cores in target cells following infection, while the catalytically inactive control and WT rhTRIM5alpha induced the abortive disassembly of viral cores, indicating a role for ubiquitin conjugation in rhTRIM5alpha-mediated destabilization of HIV-1 cores. Finally, DUb-rhTRIM5alpha failed to activate NF-kappaB signaling pathways compared to controls, demonstrating that this ubiquitination-dependent activity is separable from the ability to restrict retroviral infection. IMPORTANCE: These studies provide direct evidence that ubiquitin conjugation to rhTRIM5alpha containing complexes is required for the second step of HIV-1 restriction. They also provide a novel tool by which the biological activities of TRIM family proteins might be dissected to better understand their function and underlying mechanisms of action. PMID- 26676783 TI - Infection of a Single Cell Line with Distinct Strains of Human Cytomegalovirus Can Result in Large Variations in Virion Production and Facilitate Efficient Screening of Virus Protein Function. AB - Previously, we reported that the absence of the ataxia telangiectasia mutated (ATM) kinase, a critical DNA damage response (DDR) signaling component for double strand breaks, caused no change in HCMV Towne virion production. Later, others reported decreased AD169 viral titers in the absence of ATM. To address this discrepancy, human foreskin fibroblasts (HFF) and three ATM(-) lines (GM02530, GM05823, and GM03395) were infected with both Towne and AD169. Two additional ATM(-) lines (GM02052 and GM03487) were infected with Towne. Remarkably, both previous studies' results were confirmed. However, the increased number of cell lines and infections with both lab-adapted strains confirmed that ATM was not necessary to produce wild-type-level titers in fibroblasts. Instead, interactions between individual virus strains and the cellular microenvironment of the individual ATM(-) line determined efficiency of virion production. Surprisingly, these two commonly used lab-adapted strains produced drastically different titers in one ATM(-) cell line, GM05823. The differences in titer suggested a rapid method for identifying genes involved in differential virion production. In silico comparison of the Towne and AD169 genomes determined a list of 28 probable candidates responsible for the difference. Using serial iterations of an experiment involving virion entry and input genome nuclear trafficking with a panel of related strains, we reduced this list to four (UL129, UL145, UL147, and UL148). As a proof of principle, reintroduction of UL148 largely rescued genome trafficking. Therefore, use of a battery of related strains offers an efficient method to narrow lists of candidate genes affecting various virus life cycle checkpoints. IMPORTANCE: Human cytomegalovirus (HCMV) infection of multiple cell lines lacking ataxia telangiectasia mutated (ATM) protein produced wild-type levels of infectious virus. Interactions between virus strains and the microenvironment of individual ATM(-) lines determined the efficiency of virion production. Infection of one ATM(-) cell line, GM05823, produced large titer differentials dependent on the strain used, Towne or AD169. This discrepancy resolved a disagreement in the literature of a requirement for ATM expression and HCMV reproduction. The titer differentials in GM08523 cells were due, in part, to a decreased capacity of AD169 virions to enter the cell and traffic genomes to the nucleus. In silico comparison of the Towne, AD169, and related variant strains' genomes was coupled with serial iterations of a virus entry experiment, narrowing 28 candidate proteins responsible for the phenotype down to 4. Reintroduction of UL148 significantly rescued genome trafficking. Differential behavior of virus strains can be exploited to elucidate gene function. PMID- 26676784 TI - Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication. AB - West Nile virus (WNV) is a mosquito-transmitted flavivirus that naturally circulates between mosquitos and birds but can also infect humans, causing severe neurological disease. The early host response to WNV infection in vertebrates primarily relies on the type I interferon pathway; however, recent studies suggest that microRNAs (miRNAs) may also play a notable role. In this study, we assessed the role of host miRNAs in response to WNV infection in human cells. We employed small RNA sequencing (RNA-seq) analysis to determine changes in the expression of host miRNAs in HEK293 cells infected with an Australian strain of WNV, Kunjin (WNVKUN), and identified a number of host miRNAs differentially expressed in response to infection. Three of these miRNAs were confirmed to be significantly upregulated in infected cells by quantitative reverse transcription (qRT)-PCR and Northern blot analyses, and one of them, miR-532-5p, exhibited a significant antiviral effect against WNVKUN infection. We have demonstrated that miR-532-5p targets and downregulates expression of the host genes SESTD1 and TAB3 in human cells. Small interfering RNA (siRNA) depletion studies showed that both SESTD1 and TAB3 were required for efficient WNVKUN replication. We also demonstrated upregulation of mir-532-5p expression and a corresponding decrease in the expression of its targets, SESTD1 and TAB3, in the brains of WNVKUN infected mice. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent a host antiviral response aimed at limiting WNVKUN infection and highlight the important role of miRNAs in controlling RNA virus infections in mammalian hosts. IMPORTANCE: West Nile virus (WNV) is a significant viral pathogen that poses a considerable threat to human health across the globe. There is no specific treatment or licensed vaccine available for WNV, and deeper insight into how the virus interacts with the host is required to facilitate their development. In this study, we addressed the role of host microRNAs (miRNAs) in antiviral response to WNV in human cells. We identified miR-532-5p as a novel antiviral miRNA and showed that it is upregulated in response to WNV infection and suppresses the expression of the host genes TAB3 and SESTD1 required for WNV replication. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent an antiviral response aimed at limiting WNV infection and highlight the important role of miRNAs in controlling virus infections in mammalian hosts. PMID- 26676785 TI - Nipah Virus Matrix Protein Influences Fusogenicity and Is Essential for Particle Infectivity and Stability. AB - Nipah virus (NiV) causes fatal encephalitic infections in humans. To characterize the role of the matrix (M) protein in the viral life cycle, we generated a reverse genetics system based on NiV strain Malaysia. Using an enhanced green fluorescent protein (eGFP)-expressing M protein-deleted NiV, we observed a slightly increased cell-cell fusion, slow replication kinetics, and significantly reduced peak titers compared to the parental virus. While increased amounts of viral proteins were found in the supernatant of cells infected with M-deleted NiV, the infectivity-to-particle ratio was more than 100-fold reduced, and the particles were less thermostable and of more irregular morphology. Taken together, our data demonstrate that the M protein is not absolutely required for the production of cell-free NiV but is necessary for proper assembly and release of stable infectious NiV particles. IMPORTANCE: Henipaviruses cause a severe disease with high mortality in human patients. Therefore, these viruses can be studied only in biosafety level 4 (BSL-4) laboratories, making it more challenging to characterize their life cycle. Here we investigated the role of the Nipah virus matrix protein in virus-mediated cell-cell fusion and in the formation and release of newly produced particles. We found that even though low levels of infectious viruses are produced in the absence of the matrix protein, it is required for the release of highly infectious and stable particles. Fusogenicity of matrixless viruses was slightly enhanced, further demonstrating the critical role of this protein in different steps of Nipah virus spread. PMID- 26676786 TI - Human Cytomegalovirus Promotes Survival of Infected Monocytes via a Distinct Temporal Regulation of Cellular Bcl-2 Family Proteins. AB - Monocytes play a key role in the hematogenous dissemination of human cytomegalovirus (HCMV) to target organ systems. To infect monocytes and reprogram them to deliver infectious virus, HCMV must overcome biological obstacles, including the short life span of monocytes and their antiviral proapoptotic response to infection. We have shown that virally induced upregulation of cellular Mcl-1 promotes early survival of HCMV-infected monocytes, allowing cells to overcome an early apoptotic checkpoint at around 48 h postinfection (hpi). Here, we demonstrate an HCMV-dependent shift from Mcl-1 as the primary antiapoptotic player to the related protein, Bcl-2, later during infection. Bcl-2 was upregulated in HCMV-infected monocytes beginning at 48 hpi. Treatment with the Bcl-2 antagonist ABT-199 only reduced the prosurvival effects of HCMV in target monocytes beginning at 48 hpi, suggesting that Mcl-1 controls survival prior to 48 hpi, while Bcl-2 promotes survival after 48 hpi. Although Bcl-2 was upregulated following viral binding/signaling through cellular integrins (compared to Mcl-1, which is upregulated through binding/activation of epidermal growth factor receptor [EGFR]), it functioned similarly to Mcl-1, adopting the early role of Mcl-1 in preventing caspase-3 cleavage/activation. This distinct, HCMV-induced shift from Mcl-1 to Bcl-2 occurs in response to a cellular upregulation of proapoptotic Bax, as small interfering RNA (siRNA)-mediated knockdown of Bax reduced the upregulation of Bcl-2 in infected monocytes and rescued the cells from the apoptotic effects of Bcl-2 inhibition. Our data demonstrate a distinct survival strategy whereby HCMV induces a biphasic regulation of cellular Bcl-2 proteins to promote host cell survival, leading to viral dissemination and the establishment of persistent HCMV infection. IMPORTANCE: Hematogenous dissemination of HCMV via infected monocytes is a crucial component of the viral survival strategy and is required for the establishment of persistent infection and for viral spread to additional hosts. Our system of infected primary human blood monocytes provides us with an opportunity to answer specific questions about viral spread and persistence in in vivo-relevant myeloid cells that cannot be addressed with the more traditionally used replication-permissive cells. Our goal in examining the mechanisms whereby HCMV reprograms infected monocytes to promote viral dissemination is to uncover new targets for therapeutic intervention that would disrupt key viral survival and persistence strategies. Because of this important role in maintaining survival of HCMV-infected monocytes, our new data on the role of Bcl-2 regulation during viral infection represents a promising molecular target for mitigating viral spread and persistence. PMID- 26676787 TI - Identification of Novel Fusion Inhibitors of Influenza A Virus by Chemical Genetics. AB - A previous screening of more than 50,000 compounds led to the identification of a pool of bioactive small molecules with inhibitory effect on the influenza A virus. One of these compounds, now widely known as nucleozin, is a small molecule that targets the influenza A virus nucleoprotein. Here we identify and characterize two structurally different novel fusion inhibitors of the influenza A virus group 1 hemagglutinin (HA), FA-583 and FA-617, with low nanomolar activities. Escape mutants that are highly resistant to each of these compounds were generated, and both were found to carry mutations localized in close proximity to the B-loop of the hemagglutinin 2 protein, which plays a crucial role in the virion-host cell fusion process. Recombinant virus, generated through reverse genetics, confirmed the resistance phenotype. In addition, the proposed binding pockets predicted by molecular docking studies are in accordance with the resistance-bearing mutation sites. We show through mechanistic studies that FA 583 and FA-617 act as fusion inhibitors by prohibiting the low-pH-induced conformational change of hemagglutinin. Our study has offered concrete biological and mechanistic explorations for the strategic development of novel fusion inhibitors of influenza A viruses. IMPORTANCE: Here we report two structurally distinctive novel fusion inhibitors of influenza A virus that act by interfering with the structural change of HA at acidic pH, a process necessary for successful entry of the virus. Mutational and molecular docking studies have identified their binding pockets situated in close proximity to the B-loop region of hemagglutinin 2. The reduced sensitivity of FA-583- or FA-617-associated mutants to another compound suggests a close proximity and even partial overlap of their binding sites on hemagglutinin. Amino acid sequence alignments and crystal structure analyses of group 1 and group 2 hemagglutinins have shed light on the possible binding mode of these two compounds. This report offers new lead compounds for the design of fusion inhibitors for influenza A viruses and further shows that analysis by forward chemical genetics is a highly effective approach for the identification of novel compounds that can perturb the infectivity of viruses and to probe new druggable targets or druggable domains in various viruses. PMID- 26676788 TI - Mouse Hepatitis Virus Infection Remodels Connexin43-Mediated Gap Junction Intercellular Communication In Vitro and In Vivo. AB - Gap junctions (GJs) form intercellular channels which directly connect the cytoplasm between neighboring cells to facilitate the transfer of ions and small molecules. GJs play a major role in the pathogenesis of infection-associated inflammation. Mutations of gap junction proteins, connexins (Cxs), cause dysmyelination and leukoencephalopathy. In multiple sclerosis (MS) patients and its animal model experimental autoimmune encephalitis (EAE), Cx43 was shown to be modulated in the central nervous system (CNS). The mechanism behind Cx43 alteration and its role in MS remains unexplored. Mouse hepatitis virus (MHV) infection-induced demyelination is one of the best-studied experimental animal models for MS. Our studies demonstrated that MHV infection downregulated Cx43 expression at protein and mRNA levels in vitro in primary astrocytes obtained from neonatal mouse brains. After infection, a significant amount of Cx43 was retained in endoplasmic reticulum/endoplasmic reticulum Golgi intermediate complex (ER/ERGIC) and GJ plaque formation was impaired at the cell surface, as evidenced by a reduction of the Triton X-100 insoluble fraction of Cx43. Altered trafficking and impairment of GJ plaque formation may cause the loss of functional channel formation in MHV-infected primary astrocytes, as demonstrated by a reduced number of dye-coupled cells after a scrape-loading Lucifer yellow dye transfer assay. Upon MHV infection, a significant downregulation of Cx43 was observed in the virus-infected mouse brain. This study demonstrates that astrocytic Cx43 expression and function can be modulated due to virus stress and can be an appropriate model to understand the basis of cellular mechanisms involved in the alteration of gap junction intercellular communication (GJIC) in CNS neuroinflammation. IMPORTANCE: We found that MHV infection leads to the downregulation of Cx43 in vivo in the CNS. In addition, results show that MHV infection impairs Cx43 expression in addition to gap junction communication in primary astrocytes. After infection, Cx43 did not traffic normally to the membrane to form gap junction plaques, and that could be the basis of reduced functional gap junction coupling between astrocytes. This is an important first step toward understanding how viruses affect Cx43 expression and trafficking at the cellular level. This may provide a basis for understanding how structural alterations of astrocytic gap junctions can disrupt gap junction communication between other CNS cells in altered CNS environments due to infection and inflammation. More specifically, alteration of Cx43 may be the basis of the destabilization of Cx47 in oligodendrocytes seen in and around inflammatory demyelinating plaques in MS patients. PMID- 26676789 TI - Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains. AB - Seasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. "Universal" influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk specific and cross-reactive serum antibodies than does vaccination with VSV vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses. IMPORTANCE: Universal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination offers significantly better protection than intramuscular vaccination in a lethal virus challenge model. The results described in this study offer insights into the mechanisms by which chimeric hemagglutinin (HA)-based vaccines confer immunity, namely, that the invariant stalk of cHA antigens is superior to full-length HA antigens at inducing cross-reactive humoral immune responses and that VSV-cHA vaccine-induced protection varies by site of inoculation, and contribute to the further development of universal influenza virus vaccines. PMID- 26676790 TI - Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection. AB - Children with acute respiratory syncytial virus (RSV) infection often develop sequelae of persistent airway inflammation and wheezing. Pulmonary C fibers (PCFs) are involved in the generation of airway inflammation and resistance; however, their role in persistent airway diseases after RSV is unexplored. Here, we elucidated the pathogenesis of PCF activation in RSV-induced persistent airway disorders. PCF-degenerated and intact mice were used in the current study. Airway inflammation and airway resistance were evaluated. MMP408 and FSLLRY-NH2 were the selective antagonists for MMP-12 and PAR2, respectively, to investigate the roles of MMP-12 and PAR2 in PCFs mediating airway diseases. As a result, PCF degeneration significantly reduced the following responses to RSV infection: augmenting of inflammatory cells, especially macrophages, and infiltrating of inflammatory cells in lung tissues; specific airway resistance (sRaw) response to methacholine; and upregulation of MMP-12 and PAR2 expression. Moreover, the inhibition of MMP-12 reduced the total number of cells and macrophages in bronchiolar lavage fluid (BALF), as well infiltrating inflammatory cells, and decreased the sRaw response to methacholine. In addition, PAR2 was upregulated especially at the later stage of RSV infection. Downregulation of PAR2 ameliorated airway inflammation and resistance following RSV infection and suppressed the level of MMP-12. In all, the results suggest that PCF involvement in long-term airway inflammation and airway hyperresponsiveness occurred at least partially via modulating MMP-12, and the activation of PAR2 might be related to PCF-modulated MMP-12 production. Our initial findings indicated that the inhibition of PCF activity would be targeted therapeutically for virus infection induced long-term airway disorders. IMPORTANCE: The current study is critical to understanding that PCFs are involved in long-term airway inflammation and airway resistance after RSV infection through mediating MMP-12 production via PAR2, indicating that the inhibition of PCF activity can be targeted therapeutically for virus infection-induced long-term airway disorders. PMID- 26676791 TI - Early Activation of Primary Brain Microvascular Endothelial Cells by Nipah Virus Glycoprotein-Containing Particles. AB - Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (CNS) inflammation. Using primary porcine brain microvascular endothelial cells, we showed that upregulation of E-selectin precedes cytokine induction and is induced not only by infectious NiV but also by NiV-glycoprotein-containing virus-like particles. This demonstrates that very early events in NiV brain endothelial infection do not depend on NiV replication but can be triggered by the NiV glycoproteins alone. PMID- 26676793 TI - A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy. AB - The live attenuated influenza vaccine (LAIV) is preferentially recommended for use in most children yet remains unsafe for the groups most at risk. Here we have improved the safety of a mouse-adapted live attenuated influenza vaccine containing the same attenuating amino acid mutations as in human LAIV by adding an additional mutation at PB1 residue 319. This results in a vaccine with a 20 fold decrease in protective efficacy and a 10,000-fold increase in safety. PMID- 26676792 TI - Murine Gammaherpesvirus 68 LANA and SOX Homologs Counteract ATM-Driven p53 Activity during Lytic Viral Replication. AB - Tumor suppressor p53 is activated in response to numerous cellular stresses, including viral infection. However, whether murine gammaherpesvirus 68 (MHV68) provokes p53 during the lytic replication cycle has not been extensively evaluated. Here, we demonstrate that MHV68 lytic infection induces p53 phosphorylation and stabilization in a manner that is dependent on the DNA damage response (DDR) kinase ataxia telangiectasia mutated (ATM). The induction of p53 during MHV68 infection occurred in multiple cell types, including splenocytes of infected mice. ATM and p53 activation required early viral gene expression but occurred independently of viral DNA replication. At early time points during infection, p53-responsive cellular genes were induced, coinciding with p53 stabilization and phosphorylation. However, p53-related gene expression subsided as infection progressed, even though p53 remained stable and phosphorylated. Infected cells also failed to initiate p53-dependent gene expression and undergo apoptosis in response to treatment with exogenous p53 agonists. The inhibition of p53 responses during infection required the expression of the MHV68 homologs of the shutoff and exonuclease protein (muSOX) and latency-associated nuclear antigen (mLANA). Interestingly, mLANA, but not muSOX, was necessary to prevent p53-mediated death in MHV68-infected cells under the conditions tested. This suggests that muSOX and mLANA are differentially required for inhibiting p53 in specific settings. These data reveal that DDR responses triggered by MHV68 infection promote p53 activation. However, MHV68 encodes at least two proteins capable of limiting the potential consequences of p53 function. IMPORTANCE: Gammaherpesviruses are oncogenic herpesviruses that establish lifelong chronic infections. Defining how gammaherpesviruses overcome host responses to infection is important for understanding how these viruses infect and cause disease. Here, we establish that murine gammaherpesvirus 68 induces the activation of tumor suppressor p53. p53 activation was dependent on the DNA damage response kinase ataxia telangiectasia mutated. Although active early after infection, p53 became dominantly inhibited as the infection cycle progressed. Viral inhibition of p53 was mediated by the murine gammaherpesvirus 68 homologs of muSOX and mLANA. The inhibition of the p53 pathway enabled infected cells to evade p53-mediated cell death responses. These data demonstrate that a gammaherpesvirus encodes multiple proteins to limit p53-mediated responses to productive viral infection, which likely benefits acute viral replication and the establishment of chronic infection. PMID- 26676794 TI - ICP8 Filament Formation Is Essential for Replication Compartment Formation during Herpes Simplex Virus Infection. AB - Herpes simplex virus (HSV) dramatically reorganizes the infected-cell nucleus, leading to the formation of prereplicative sites and replication compartments. This process is driven by the essential viral single-stranded DNA (ssDNA) binding protein ICP8, which can form double-helical filaments in the absence of DNA. In this paper, we show that two conserved motifs, FNF (F1142, N1143, and F1144) and FW (F843 and W844), are essential for ICP8 self-interactions, and we propose that the FNF motif docks into the FW region during filament formation. Mammalian expression plasmids bearing mutations in these motifs (FNF and FW) were unable to complement an ICP8-null mutant for growth and replication compartment formation. Furthermore, FNF and FW mutants were able to inhibit wild-type (WT) virus plaque formation and filament formation, whereas a double mutant (FNF-FW) was not. These results suggest that single mutant proteins are incorporated into nonproductive ICP8 filaments, while the double mutant is unable to interact with WT ICP8 and does not interfere with WT growth. Cells transfected with WT ICP8 and the helicase-primase (H/P) complex exhibited punctate nuclear structures that resemble prereplicative sites; however, the FNF and FW mutants failed to do so. Taken together, these results suggest that the FNF and FW motifs are required for ICP8 self-interactions and that these interactions may be important for the formation of prereplicative sites and replication compartments. We propose that filaments or other higher-order structures of ICP8 may provide a scaffold onto which other proteins can be recruited to form prereplicative sites and replication compartments. IMPORTANCE: For nuclear viruses such as HSV, efficient DNA replication requires the formation of discrete compartments within the infected-cell nucleus in which replication proteins are concentrated and assembled into the HSV replisome. In this paper, we characterize the role of filament formation by the single-stranded DNA binding protein ICP8 in the formation of prereplicative sites and replication compartments. We propose that ICP8 protein filaments generate a protein scaffold for other cellular and viral proteins, resulting in a structure that concentrates both viral DNA and replication proteins. Replication compartments may be similar to other types of cellular membraneless compartments thought to be formed by phase separations caused by low-affinity, multivalent interactions involving proteins and nucleic acids within cells. ICP8 scaffolds could facilitate the formation of replication compartments by mediating interactions with other components of the replication machinery. PMID- 26676796 TI - Disseminating Justified, Well-Designed, and Well-Executed Studies With Nonsignificant Tests--Reply. PMID- 26676795 TI - A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose. AB - Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growth in vitro and expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a prime-and-boost vaccination strategy. IMPORTANCE: We have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this live rP18tri vector to be used as a novel vaccine platform for a prime-and-boost vaccination strategy. PMID- 26676797 TI - The Microbiome and Musculoskeletal Conditions of Aging: A Review of Evidence for Impact and Potential Therapeutics. AB - Recently, we have begun to realize that the billions of microorganisms living in symbiosis with us have an influence on disease. Evidence is mounting that the alimentary tract microbiome, in particular, influences both host metabolic potential and its innate and adaptive immune system. Inflammatory states characterize many bone and joint diseases of aging. This prompts the hypothesis that the gut microbiome could alter the inflammatory state of the individual and directly influence the development of these common and burdensome clinical problems. Because the microbiome is easily modifiable, this could have major therapeutic impact. This perspective discusses evidence to date on the role of the microbiome and the highly prevalent age-related disorders of osteoporosis, osteoarthritis, gout, rheumatoid arthritis, sarcopenia, and frailty. It also reviews data on the effects of probiotics and prebiotic interventions in animal and human models. Despite suggestive findings, research to date is not conclusive, and we identify priorities for research to substantiate and translate findings. PMID- 26676798 TI - Space invaders - A netnographic study of how artefacts in nursing home environments exercise disciplining structures. AB - This study aims to present culturally situated artefacts as depicted in nursing home environments and to analyse the underlying understandings of disciplining structures that are manifested in these kinds of places. Our personal geographies are often taken for granted, but when moving to a nursing home, geographies are glaringly rearranged. The study design is archival and cross-sectional observational, and the data are comprised of 38 photographs and 13 videos showing environments from nursing homes. The analysis was inspired by the methodological steps in Roper's and Shapira's description of conducting ethnography. The results are presented in four categories: (i) public areas, (ii) orderliness, (iii) staff's places and (iv) devices. The rearrangement of geography implies a degrading of agency and loss of authority over one's place. The places should be understood in their relation to the agents and their temporarily claims upon them. The material and immaterial artefacts, that is the items, people and behaviours, transform the nursing staff into 'space invaders'. Future inquiries may take into consideration the ways that space invasion in participative space intersect and construct the identities of the agents it invades upon. PMID- 26676799 TI - Plant cell wall imaging by metabolic click-mediated labelling of rhamnogalacturonan II using azido 3-deoxy-D-manno-oct-2-ulosonic acid. AB - In plants, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan-II (RG-II). Incubation of 4-day-old light-grown Arabidopsis seedlings or tobacco BY-2 cells with 8-azido 8 deoxy Kdo (Kdo-N3 ) followed by coupling to an alkyne-containing fluorescent probe resulted in the specific in muro labelling of RG-II through a copper catalysed azide-alkyne cycloaddition reaction. CMP-Kdo synthetase inhibition and competition assays showing that Kdo and D-Ara, a precursor of Kdo, but not L-Ara, inhibit incorporation of Kdo-N3 demonstrated that incorporation of Kdo-N3 occurs in RG-II through the endogenous biosynthetic machinery of the cell. Co localisation of Kdo-N3 labelling with the cellulose-binding dye calcofluor white demonstrated that RG-II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo-N3 and an alkynated derivative of L-fucose that incorporates into rhamnogalacturonan I, co-localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click-mediated labelling with Kdo-N3 provides an efficient method to study the synthesis and redistribution of RG-II during root growth. PMID- 26676800 TI - 2D Transition-Metal-Dichalcogenide-Nanosheet-Based Composites for Photocatalytic and Electrocatalytic Hydrogen Evolution Reactions. AB - Hydrogen (H2) is one of the most important clean and renewable energy sources for future energy sustainability. Nowadays, photocatalytic and electrocatalytic hydrogen evolution reactions (HERs) from water splitting are considered as two of the most efficient methods to convert sustainable energy to the clean energy carrier, H2. Catalysts based on transition metal dichalcogenides (TMDs) are recognized as greatly promising substitutes for noble-metal-based catalysts for HER. The photocatalytic and electrocatalytic activities of TMD nanosheets for the HER can be further improved after hybridization with many kinds of nanomaterials, such as metals, oxides, sulfides, and carbon materials, through different methods including the in situ reduction method, the hot-injection method, the heating-up method, the hydro(solvo)thermal method, chemical vapor deposition (CVD), and thermal annealing. Here, recent progress in photocatalytic and electrocatalytic HERs using 2D TMD-based composites as catalysts is discussed. PMID- 26676801 TI - Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo. AB - In the present study, we aimed to investigate the relationship between autophagy and apoptosis in selenite-treated colorectal cancer (CRC) cells. The effects of selenite on HCT116 and SW480 cell apoptosis were investigated with an Annexin V/propidium iodide (PI) double staining kit by flow cytometry. The punctate of LC3 protein following treatment with selenite was observed by a laser scanning confocal microscope and by transmission electron microscopy. Using western blot assays, we detected the apoptotic and autophagic markers in both CRC cells and mouse xenograft tumor models. We found that sodium selenite induced autophagy in the two CRC cell lines. Consistent with the in vitro results, we observed that the expression of autophagy marker LC3 was increased. Finally, we discovered that modulation of reactive oxygen species by MnTMPyP inhibited autophagy, while H2O2 activated autophagy. These results help to elucidate the anticancer effect of selenium, providing further evidence to exploit novel anticancer drugs targeting selenium. PMID- 26676802 TI - Functional assessment and structural basis of antibody binding to human papillomavirus capsid. AB - Persistent high-risk human papillomavirus (HPV) infection is linked to cervical cancer. Two prophylactic virus-like particle (VLP)-based vaccines have been marketed globally for nearly a decade. Here, we review the HPV pseudovirion (PsV) based assays for the functional assessment of the HPV neutralizing antibodies and the structural basis for these clinically relevant epitopes. The PsV-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited by vaccination or natural infection or to assess the functional characteristics of monoclonal antibodies. Different antibody binding modes were observed when an antibody was complexed with virions, PsVs or VLPs. The neutralizing epitopes are localized on surface loops of the L1 capsid protein, at various locations on the capsomere. Different neutralization antibodies exert their neutralizing function via different mechanisms. Some antibodies neutralize the virions by inducing conformational changes in the viral capsid, which can result in concealing the binding site for a cellular receptor like 1A1D-2 against dengue virus, or inducing premature genome release like E18 against enterovirus 71. Higher-resolution details on the epitope composition of HPV neutralizing antibodies would shed light on the structural basis of the highly efficacious vaccines and aid the design of next generation vaccines. In depth understanding of epitope composition would ensure the development of function-indicating assays for the comparability exercise to support process improvement or process scale up. Elucidation of the structural elements of the type-specific epitopes would enable rational design of cross-type neutralization via epitope re-engineering or epitope grafting in hybrid VLPs. PMID- 26676804 TI - Molecular genetic and cytogenetic analysis of a primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma. AB - We performed cytogenetic and molecular cytogenetic analyses of a primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, a rare type of primary cutaneous T-cell lymphoma. G-banded analysis at initial diagnosis and recurrence revealed complex karyotype and clonal evolution reflecting genomic instability that parallels the aggressive clinical course observed. Spectral karyotyping revealed numerous structural abnormalities. SNP array-based analysis of an initial diagnostic sample revealed numerous gains and losses of chromosomal material, including loss of short arm of the chromosome 17, to which TP53 is mapped. The molecular cytogenetics and array data of this case suggest genomic instability, particularly chromosomal instability and haploinsufficiency for TP53, the latter possibly giving rise to alteration of p14ARF-Mdm2-p53 tumor suppressor protein pathway, likely to be associated with unfavorable clinical course. PMID- 26676803 TI - Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation. AB - Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation. PMID- 26676806 TI - The Role of Neuromediators and Innervation in Cutaneous Wound Healing. AB - The skin is densely innervated with an intricate network of cutaneous nerves, neuromediators and specific receptors which influence a variety of physiological and disease processes. There is emerging evidence that cutaneous innervation may play an important role in mediating wound healing. This review aims to comprehensively examine the evidence that signifies the role of innervation during the overlapping stages of cutaneous wound healing. Numerous neuropeptides that are secreted by the sensory and autonomic nerve fibres play an essential part during the distinct phases of wound healing. Delayed wound healing in diabetes and fetal cutaneous regeneration following wounding further highlights the pivotal role skin innervation and its associated neuromediators play in wound healing. Understanding the mechanisms via which cutaneous innervation modulates wound healing in both the adult and fetus will provide opportunities to develop therapeutic devices which could manipulate skin innervation to aid wound healing. PMID- 26676805 TI - Prospective isolation of resident adult human mesenchymal stem cell population from multiple organs. AB - Mesenchymal stem/stromal cells (MSCs) have the potential to form colonies in culture and reside in adult tissues. Because MSCs have been defined using cells cultured in vitro, discrepancies have arisen between studies concerning their properties. There are also differences between populations obtained using different isolation methods. This review article focuses on recent developments in the identification of novel MSC markers for the in vivo localization and prospective isolation of human MSCs. The prospective isolation method described in this study represents an important strategy for the isolation of MSCs in a short period of time, and may find applications for regenerative medicine. Purified MSCs can be tailored according to their intended clinical therapeutic applications. Lineage tracing methods define the MSC phenotype and can be used to investigate the physiological roles of MSCs in vivo. These findings may facilitate the development of effective stem cell treatments. PMID- 26676807 TI - Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells. AB - Taxanes, paclitaxel and docetaxel (DTX) are anticancer agents that exhibit cytotoxicity by inhibiting microtubule polymerization. They enhance the radiosensitivity of various cancers by blocking the cell cycle in the most radiosensitive G2/M phase. Recently, taxanes have been reported to have different mechanisms of action depending on dose intensity. However, the mechanism of the radio-enhancing effect of DTX in relation to the drug dose intensity is not clearly understood. In the present study, we experimentally investigated the radio-enhancing effects of various concentrations of DTX against esophageal squamous cell cancer (ESCC); KES cells were used for in vitro confirmation of the effective administration schedule for DTX in chemoradiotherapy involving ESCC. DTX enhanced radiation cell killing in a concentration-dependent manner in KES cells. High cytotoxic concentrations (>10 nM) of DTX strongly enhanced radiosensitivity. Low concentrations (<1 nM) of DTX that did not have a cytotoxic effect showed a radio-enhancing effect by inducing DNA double strand breaks and apoptosis after irradiation. Low and high concentrations of DTX induced radiosensitive G0/G1 and G2/M phase arrest, respectively in KES cells. Cells treated with high concentrations of DTX exhibited nuclear aggregation associated with apoptotic change. In contrast, cells treated with low concentrations of DTX displayed multi-nucleation or unequal division. In conclusion, enhancement of the radiosensitivity of ESCC cells by DTX was demonstrated, even using nanomolar concentrations that did not have a cytotoxic effect. DTX has different radio enhancing mechanisms depending on its concentration. Therefore, weekly administration of DTX might effectively enhance radiation cytotoxicity in the treatment of ESCC. PMID- 26676808 TI - Infliximab-induced autoantibodies: a multicenter study. AB - The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was discontinued. Infliximab induced the formation of autoantibodies in the combined population (ANA and anti-dsDNA with no apparent clinical importance). PMID- 26676809 TI - The association between serious infection and disease outcome in patients with rheumatoid arthritis. AB - The purpose of this study was to study the association between the past history of serious infection (SI) that required hospitalization and the current disease status of rheumatoid arthritis (RA), including disease activity, physical disability, and radiological joint destruction. The history of hospitalized infection was retrospectively analyzed in a cohort of 370 RA patients. The patients were divided into three groups based on the number of SI events (SI = 0, SI = 1, SI >= 2). Disease activity score using 28 joints (DAS28), Health Assessment Questionnaire (HAQ), and modified total sharp score (mTSS) adjusted after disease duration or other confounding factors were compared among the three groups. Among the study patients, 7.3% (27 patients) experienced single SI (SI = 1) and 2.1% (8 patients) experienced multiple SI events (SI >= 2). Compared with patients with no SI (SI = 0), patients with SI (SI = 1 or SI >= 2) had increased pulmonary and autoimmune comorbidities and were more frequently treated with glucocorticoids. DAS28 was not different among the groups, while HAQ and mTSS increased with the number of SI. After adjustment, only mTSS adjusted after disease duration remained statistically significantly different between patients with SI = 0 and SI >= 2 (p = 0.030). Multiple SI events are associated with advanced physical disability and radiological joint destruction in patients with RA. PMID- 26676810 TI - A meta-analysis to determine the effect of pharmacological and non pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria. AB - Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT 10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment. PMID- 26676811 TI - Genome-Wide Association Studies and Liver Disease. PMID- 26676812 TI - Genetics of Alcoholic Liver Disease. AB - Excess alcohol consumption with consequent alcoholic liver disease (ALD) is a common cause of liver dysfunction and liver-related mortality worldwide. However, although the majority of heavy drinkers will develop steatosis, only a minority progress to advanced liver disease and cirrhosis. Thus, ALD is a complex disease where subtle interpatient genetic variations and environmental factors interact to determine disease progression. One genome-wide association study specifically addressing genetic modifiers of ALD has been published. However, most of our understanding is based on studies conducted on nonalcoholic fatty liver disease. Translation of candidates from these studies into ALD has established a role for variants in genes including PNPLA3 and potentially TM6SF2 across the disease spectrum from steatosis, through cirrhosis to hepatocellular carcinoma. Here the authors review the current status of the field with a particular focus on recent advances. PMID- 26676815 TI - Genome-Wide Association Studies and Hepatitis C: Harvesting the Benefits of the Genomic Revolution. AB - Utilizing genome-wide association studies (GWASs) to examine the variation in hepatitis C virus (HCV) phenotypes has led to quantum improvements in our understanding of both the genetic basis and the underlying pathogenesis of HCV infection. In this context, the discovery of interferon lambda polymorphisms is unique with far reaching implications that extend well beyond HCV to various other liver and extrahepatic diseases. In this review, we summarize the data on the impact of GWASs on our understanding of HCV disease. PMID- 26676816 TI - Genome-Wide Association Studies in Drug-Induced Liver Injury: Step Change in Understanding the Pathogenesis. AB - Hepatotoxicity constrains drug development and accounts for a substantial burden on health services. Genome-wide association studies (GWASs) have investigated potential genetic factors that explain interindividual variations in response to medications leading to drug-induced liver injury (DILI). Although the proportion of GWASs investigating DILI is very small, those that have focused on this area have identified risk alleles with substantially higher risk ratios for susceptibility to DILI when compared with GWASs involving the majority of other complex diseases. Moreover, a relatively small number of human leukocyte antigen alleles are associated with DILI secondary to a range of medications. Because the encoded major histocompatibility complex proteins mediate antigen presentation to T cells, this provides evidence for a crucial central role for the adaptive immune system in DILI. Findings of GWASs should be considered during preclinical development of certain drugs. Genotyping may also have clinical applications, although it is currently limited to particular scenarios in relation to specific drugs. PMID- 26676813 TI - Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID- 26676814 TI - Genome-Wide Association Studies in Primary Biliary Cirrhosis. AB - Genome-wide association studies (GWASs) have been a significant technological advance in our ability to evaluate the genetic architecture of complex diseases such as primary biliary cirrhosis (PBC). To date, six large-scale studies have been performed that have identified 27 risk loci in addition to human leukocyte antigen (HLA) associated with PBC. The identified risk variants emphasize important disease concepts; namely, that disturbances in immunoregulatory pathways are important in the pathogenesis of PBC and that such perturbations are shared among a diverse number of autoimmune diseases-suggesting the risk architecture may confer a generalized propensity to autoimmunity not necessarily specific to PBC. Furthermore, the impact of non-HLA risk variants, particularly in genes involved with interleukin-12 signaling, and ethnic variation in conferring susceptibility to PBC have been highlighted. Although GWASs have been a critical stepping stone in understanding common genetic variation contributing to PBC, limitations pertaining to power, sample availability, and strong linkage disequilibrium across genes have left us with an incomplete understanding of the genetic underpinnings of disease pathogenesis. Future efforts to gain insight into this missing heritability, the genetic variation that contributes to important disease outcomes, and the functional consequences of associated variants will be critical if practical clinical translation is to be realized. PMID- 26676817 TI - Commentary on Diagnostic Problems in Hepatology Cases. PMID- 26676818 TI - Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review. AB - Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed. PMID- 26676819 TI - Hepatic Fibrinogen Storage Disease in a Patient with Hypofibrinogenemia: Report of a Case with a Missense Mutation of the FGA Gene. AB - We report a 9-year-old patient with abnormal liver tests found incidentally during routine bloodwork as part of a preoperative evaluation for excision of a benign cyst. A liver biopsy demonstrated hepatocytes to have pale and expanded cytoplasm that contained multiple vague globular eosinophilic inclusions. Electron microscopy showed fingerprint-like structures in the dilated cisternae of the rough endoplasmic reticulum, characteristic of fibrinogen. Whole exome sequencing identified a heterozygous missense mutation at codon 35 of the fibrinogen alpha (FGA) gene. No mutation was identified in the beta or gamma chains. His plasma fibrinogen levels were found to be decreased to 85 mg/dL (normal range 215-464). His family history was pertinent for his mother and maternal grandfather with hypofibrinogenemia. He had not had any significant bleeding episodes except for minor bruising over the shins. This case illustrates a rare etiology of storage disease that causes abnormal liver function tests. PMID- 26676820 TI - Hepatocellular Carcinoma Arising in an HNF-1alpha-Mutated Adenoma in a 23-Year Old Woman with Maturity-Onset Diabetes of the Young: A Case Report. AB - Hepatocyte nuclear factor-1alpha mutated hepatocellular adenomas (H-HCA) are thought to have no to minimal malignant potential. This report describes a 23 year-old woman with maturity-onset diabetes of the young who developed a 12.5-cm hepatic mass with a radiographically and pathologically distinct 3.0-cm region. Histologically and immunohistochemically, the bulk of the mass was an H-HCA with extensive pseudoglandular formation and only focal steatosis. The 3.0-cm nodule showed small cell change, thickened hepatocyte plates, pleomorphic and hyperchromatic nuclei, reticulin loss, and stromal and vascular invasion, diagnostic of hepatocellular carcinoma (HCC). Immunohistochemically, increased expression of glutamine synthetase in tumor cells and CD34 expression in sinusoidal endothelial cells were seen in the HCC component. Nuclear expression of beta-catenin, and exon 3 of CTNNB1 and TERT promoter mutations were absent in this case. Thus, we report a HCC arising in an H-HCA; although cases appear exceedingly rare, they reinforce the potential of H-HCA for malignant transformation. PMID- 26676821 TI - Hepatocellular Carcinoma in Noncirrhotic Liver with Glycogenotic Foci: Basic Science Meets Genomic Medicine. AB - During the past decade, the application of genomic analysis to liver tumors has provided extensive data concerning tumor phenotypes, signatures, outcomes, and prognosis. In this report the authors describe a middle-aged man without known risk factors for liver disease or hepatocellular carcinoma (HCC) who developed a 19-cm HCC in his right lobe. The underlying liver was normal histologically except for multifocal glycogenotic foci similar to those found in experimental chemical carcinogenesis. Precision genomic analysis of this tumor disclosed five alterations with amplifications of genes CCNE1, FGF3 and FGF4, MYCL1, and ARID1A. The roles of these gene mutations and their potential effects in carcinogenesis in this case are discussed. PMID- 26676822 TI - Foucault's legacy for nursing: are we beneficiaries or intestate heirs? AB - Drawing upon selected literature from the United Kingdom, Denmark, and Canada we examine how Foucault's concepts of 'episteme', 'rupture' 'parrhesia' 'care of the self', and 'problemitization' have been applied to particular contexts of leadership development, pedagogy, nursing knowledge, and the relationship between caring and politics. Our aims are threefold: to give examples of how selected Foucauldian concepts have been taken up in practice; to clarify how we are positioned today as nurses; and to invite more nurses to engage critically with historical inquiry and to engage in deep philosophical reflection about their relationship with nursing. We begin by examining the conditions and circumstances of Foucault's life, and conclude by posing the question in our subtitle to stimulate debate about the philosophical relevance of Foucauldian scholarship to nursing. PMID- 26676823 TI - Unraveling the distinctive features of hemorrhagic and non-hemorrhagic snake venom metalloproteinases using molecular simulations. AB - Snake venom metalloproteinases are important toxins that play fundamental roles during envenomation. They share a structurally similar catalytic domain, but with diverse hemorrhagic capabilities. To understand the structural basis for this difference, we build and compare two dynamical models, one for the hemorrhagic atroxlysin-I from Bothrops atrox and the other for the non-hemorraghic leucurolysin-a from Bothrops leucurus. The analysis of the extended molecular dynamics simulations shows some changes in the local structure, flexibility and surface determinants that can contribute to explain the different hemorrhagic activity of the two enzymes. In agreement with previous results, the long Omega loop (from residue 149 to 177) has a larger mobility in the hemorrhagic protein. In addition, we find some potentially-relevant differences at the base of the S1' pocket, what may be interesting for the structure-based design of new anti-venom agents. However, the sharpest differences in the computational models of atroxlysin-I and leucurolysin-a are observed in the surface electrostatic potential around the active site region, suggesting thus that the hemorrhagic versus non-hemorrhagic activity is probably determined by protein surface determinants. PMID- 26676824 TI - The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes. AB - AIMS/HYPOTHESIS: Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. METHODS: The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies. RESULTS: Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p = 0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p = 0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry. CONCLUSIONS/INTERPRETATION: Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention. PMID- 26676825 TI - Characterization of the immune response in ganglia after primary simian varicella virus infection. AB - Primary simian varicella virus (SVV) infection in non-human primates causes varicella, after which the virus becomes latent in ganglionic neurons and reactivates to cause zoster. The host response in ganglia during establishment of latency is ill-defined. Ganglia from five African green monkeys (AGMs) obtained at 9, 13, and 20 days post-intratracheal SVV inoculation (dpi) were analyzed by ex vivo flow cytometry, immunohistochemistry, and in situ hybridization. Ganglia at 13 and 20 dpi exhibited mild inflammation. Immune infiltrates consisted mostly of CD8(dim) and CD8(bright) memory T cells, some of which expressed granzyme B, and fewer CD11c(+) and CD68(+) cells. Chemoattractant CXCL10 transcripts were expressed in neurons and infiltrating inflammatory cells but did not co-localize with SVV open reading frame 63 (ORF63) RNA expression. Satellite glial cells expressed increased levels of activation markers CD68 and MHC class II at 13 and 20 dpi compared to those at 9 dpi. Overall, local immune responses emerged as viral DNA load in ganglia declined, suggesting that intra-ganglionic immunity contributes to restricting SVV replication. PMID- 26676827 TI - Molecular mechanism for cyclic generation of somites: Lessons from mice and zebrafish. AB - The somite is the most prominent metameric structure observed during vertebrate embryogenesis, and its metamerism preserves the characteristic structures of the vertebrae and muscles in the adult body. During vertebrate somitogenesis, sequential formation of epithelialized cell boundaries generates the somites. According to the "clock and wavefront model," the periodical and sequential generation of somites is achieved by the integration of spatiotemporal information provided by the segmentation clock and wavefront. In the anterior region of the presomitic mesoderm, which is the somite precursor, the orchestration between the segmentation clock and the wavefront achieves morphogenesis of somites through multiple processes such as determination of somite boundary position, generation of morophological boundary, and establishment of the rostrocaudal polarity within a somite. Recently, numerous studies using various model animals including mouse, zebrafish, and chick have gradually revealed the molecular aspect of the "clock and wavefront" model and the molecular mechanism connecting the segmentation clock and the wavefront to the multiple processes of somite morphogenesis. In this review, we first summarize the current knowledge about the molecular mechanisms underlying the clock and the wavefront and then describe those of the three processes of somite morphogenesis. Especially, we will discuss the conservation and diversification in the molecular network of the somitigenesis among vertebrates, focusing on two typical model animals used for genetic analyses, i.e., the mouse and zebrafish. In this review, we described molecular mechanism for the generation of somites based on the spatiotemporal information provided by "segmentation clock" and "wavefront" focusing on the evidences obtained from mouse and zebrafish. PMID- 26676826 TI - Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy. AB - This study aims to determine the risk factors for epileptogenesis and characteristics of seizures in patients with progressive multifocal leukoencephalopathy (PML) who survive more than 1 year from onset of neurological symptoms (PML survivors). We reviewed clinical data including seizure history and MR imaging studies from PML survivors evaluated at our institution between 1997 and 2014. PML progressors who passed away within 1 year and patients with a history of seizures prior to PML diagnosis were excluded from the analysis. Of 64 PML survivors, 28 (44 %) developed seizures. The median time from the onset of PML symptoms to the first seizure was 5.4 months (range 0-159) and 64 % of patients with seizures had them within the first year. The presence of juxtacortical PML lesions was associated with a relative risk of seizures of 3.5 (p < 0.02; 95 % confidence interval (CI) 1.3-9.4) in multivariate analyses. Of all seizure types, 86 % were focal and 60 % most likely originated from the frontal lobes. Among seizure patients, 89 % required treatment, including one (54 %), two (25 %), or three (10.5 %) antiepileptic drugs. Seizures are a frequent complication in PML and can develop throughout the entire course of the disease. However, late onset seizures did not signify PML relapse. Seizures may require treatment with multiple antiepileptic medications and are a significant co morbidity in PML. PMID- 26676828 TI - Discrimination of some European vinegars with protected denomination of origin as a function of their amino acid and biogenic amine content. AB - BACKGROUND: Twenty-three amino acids and 11 amines were quantified in 37 premium quality European vinegars (traditional balsamic vinegar of Modena, balsamic vinegars of Modena and vinegars of Jerez) by an HPLC-DAD method after derivatisation with diethyl ethoxymethylenmalonate. Data were assessed in the light of the differences in technology and raw materials. RESULTS: The total amount of amino acids ranged from 136 mg kg(-1) to 1450 mg kg(-1) in traditional balsamic vinegar of Modena and balsamic vinegar of Modena, respectively. Jerez vinegars had a mean content from 351 mg kg(-1) to 921 mg kg(-1) . Proline, glycine and gamma-aminobutyric acid were the main amino acids while isoleucine was only found in balsamic vinegar of Modena at a concentration of <1 mg kg(-1) . Traditional balsamic vinegar of Modena had the lowest amount of biogenic amines. However, for all the vinegars, their concentration did not raise health issues. Based on the entire dataset, samples were successfully segregated and classified by means of principal component and cluster analysis. CONCLUSION: The amino acid and amine content in vinegars is influenced by the production process and raw materials. They may potentially contribute in characterising the European premium quality vinegars also for authentication or anti-fraud purposes. (c) 2015 Society of Chemical Industry. PMID- 26676829 TI - 1,25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1). AB - Vitamin D, termed 1,25(OH)2D3 in it's active form, activity is associated with a reduced risk of hepatocellular carcinoma (HCC) and is an important immune regulator. However, the detail molecular mechanisms underlying the effects of 1,25(OH)2D3 on the progression of HCC are widely unknown. Histone deacetwylase 2 (HDAC2) is usually expressed at high levels in tumors, and its downregulation leads to high expression levels of cell cycle components, including p21(WAF1/Cip1), a well-characterized modulator, which is critical in cell senescence and apoptosis. The present study investigated whether vitamin D inhibits HCC via the regulation of HDAC2 and p21(WAF1/Cip1). Firstly, the toxic concentrations of 1,25(OH)2D3 were determined, according to trypan blue and [(3)H]thymidine incorporation assays. Secondly, HCC cells lines were treated with different concentrations of 1,25(OH)2D3. The expression of HDAC2 was either silenced via short hairpin (sh)RNA or induced by transfection of plasmids expressing the HDAC2 gene in certain HCC cells. Finally the mRNA and protein levels of HDAC2 and p21(WAF1/Cip1) were measured using reverse transcription quantitative polymerase chain reaction and western blot analyses. The results revealed that 1,25(OH)2D3 treatment reduced the expression of HDAC2 and increased the expression of p21(WAF1/Cip1), in a dose-dependent manner, resulting in the reduction of HCC growth. Elevated levels of HDAC2 reduced the expression of p21(WAF1/Cip1), resulting in an increase in HCC growth. HDAC2 shRNA increased the expression of p21(WAF1/Cip1), resulting in reduction in HCC growth. Thus, 1,25(OH)2D3 exerted antitumorigenic effects through decreasing the expression levels of HDAC2 and increasing the expression of p21(WAF1/Cip1), which inhibited the development of HCC and may indicate the possible underlying mechanism. These results suggest that vitamin D3 may be developed as a potential drug for effective therapy in the treatment of HCC. PMID- 26676830 TI - Operative hysteroscopy for treatment of intrauterine pathologies does not interfere with later endometrial development in patients undergoing in vitro fertilization. AB - PURPOSE: Operative hysteroscopy procedure is extensively used for the treatment of intrauterine abnormalities that can potentially cause infertility. To date, there are little data addressing the effect of operative hysteroscopy that applies electrical current for excision and its subsequent effect on endometrial thickness. This study was aimed to assess the effect of thermal resection used in operative hysteroscopy on endometrial thickness and on fertility outcome in women undergoing in vitro fertilization (IVF). METHODS: A retrospective study conducted at Hadassah-Hebrew University Medical Center, a tertiary referral center. Included were IVF women who underwent an operative hysteroscopy throughout the years 2000-2010 for intrauterine pathologies. RESULTS: Throughout the years 2000 2010, 41 IVF women who underwent an operative hysteroscopy using electric current between their 82 IVF cycles were studied. The mean age of women at the time of the intervention was 37.1 years (36.7 and 37.5 at the IVF cycles before and after intervention, respectively). The maximal endometrial thickness before operative hysteroscopy was 10.7 mm compared to 9.5 mm after all procedures (P < 0.001). Excluding polypectomy cases (n = 24) the endometrial thickness was 9.9 mm before vs. 9.1 mm after operative hysteroscopy (P < 0.001). The clinical pregnancy rate was 19.5 % before as compared to 24.4 % after operative hysteroscopy (NS). The take home baby rate (THBR), however, was significantly increased following operative hysteroscopy for all indications from 2.4 to 12.2 % (P < 0.05). CONCLUSION: Despite the small change in endometrial thickness, our results indicate that using electric current is safe to treat intrauterine pathologies. PMID- 26676831 TI - Preoperative HBA1c and risk of postoperative complications in patients with gynaecological cancer. AB - BACKGROUND: HBA1c is used as an indicator for the long-term control of the glycaemic state and outcome predictors in diabetic patients. Diabetic patients have an increased risk of post-operative complications especially those related to infection. The aim of our study is to ascertain the relationship between HBA1c levels and post-operative recovery within the subspecialty of gynaecological oncology. METHOD: Prospective cohort study during the period 1 August 2012 through 31 August 2014. Preoperative measurement of HBA1c on all gynaecological oncology patients that underwent major surgery. Patient variables collected and analysed were BMI (kg/m(2)), length of stay (LOS in days), cancer stage (stage 1 through stage 4), infective complications, non-infective complications and readmission to hospital. RESULTS: A total of 300 patients were included in our study, 34 of them were known to be diabetic while 266 were presumed to be non diabetic. Of the presumed non-diabetic cohort, 17.3 % (46/266) had impaired glucose tolerance or diabetes. Mean BMI was significantly increased in the pre existing diabetic group (32.8 vs. 29.3 kg/m(2), p = 0.016). Infective complications were almost double the rate amongst the known diabetic women than those presumed to be non-diabetic (32.4 vs. 18.0 %, p = 0.048). Rate of re admission to hospital due to complications was 20.6 % in the diabetic group and 4.1 % within the presumed non-diabetic group (p < 0.001). Infective complications occurred in 16.9 % of women with HBA1c <42 mmol/mol, 22.7 % of those with HBA1c of 42-47 mmol/mol, 43.5 % of patients with HBA1c 48-64 mmol/mol and 37.5 % of patients with HBA1c >64 mmol/mol. Non-infective complications were also more frequent in women with elevated HBA1c (11.1, 22.7, 26.1 and 12.5 % in those women with HBA1c <42, 42-47, 48-64 and >64 mmol/mol, respectively). Re-admission to hospital within 30 days for a complication of surgery occurred in 4.4 % of women with HBA1c <42 mmol/mol, 4.5 % of women with HBA1c measured at 42-47 mmol/mol, 30.8 % of those with HBA1c 48-64 mmol/mol and 25 % of women with HBA1c >64 mmol/mol. CONCLUSION: Preoperative measurement of HBA1c may identify patients (both diabetic and non-diabetic women) at higher risk of postoperative complications and could be used as a trigger for modification of the perioperative management of such patients. PMID- 26676833 TI - Methylprednisolone-induced liver injury: Case report and literature review. PMID- 26676834 TI - Palladium-Catalyzed C(sp(2))-H Alkylation of Aldehyde-Derived Hydrazones with Functionalized Difluoromethyl Bromides. AB - A palladium-catalyzed C(sp(2))-H difluoromethylation of aldehyde-derived hydrazones using bromodifluoromethylated compounds to afford the corresponding functionalized difluoromethylketone hydrazones has been established. It is proposed that a radical/SET mechanism proceeding via a difluoroalkyl radical may be involved in the catalytic cycle. Applications of the methodology to the synthesis of alpha,alpha-difluoro-beta-ketoesters and alpha,alpha-difluoroketones (RCOCF2 H) have been illustrated. PMID- 26676832 TI - How To Design a Successful p53-MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures. AB - A recent therapeutic strategy in oncology is based on blocking the protein protein interaction between the murine double minute (MDM) homologues MDM2/X and the tumor-suppressor protein p53. Inhibiting the binding between wild-type (WT) p53 and its negative regulators MDM2 and/or MDMX has become an important target in oncology to restore the antitumor activity of p53, the so-called guardian of our genome. Interestingly, based on the multiple disclosed compound classes and structural analysis of small-molecule-MDM2 adducts, the p53-MDM2 complex is perhaps the best studied and most targeted protein-protein interaction. Several classes of small molecules have been identified as potent, selective, and efficient inhibitors of the p53-MDM2/X interaction, and many co-crystal structures with the protein are available. Herein we review the properties as well as preclinical and clinical studies of these small molecules and peptides, categorized by scaffold type. A particular emphasis is made on crystallographic structures and the observed binding modes of these compounds, including conserved water molecules present. PMID- 26676835 TI - Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence. AB - IMPORTANCE: The trajectory of cortical gray matter development in childhood has been characterized by early neurogenesis and volume increase, peaking at puberty followed by selective elimination and myelination, resulting in volume loss and thinning. This inverted U-shaped trajectory, as well as cortical thickness, has been associated with cognitive and emotional function. Synaptic pruning-based volume decline has been related to experience-dependent plasticity in animals. To date, there have been no data to inform whether and how childhood depression might be associated with this trajectory. OBJECTIVE: To examine the effects of early childhood depression, from the preschool age to the school age period, on cortical gray matter development measured across 3 waves of neuroimaging from late school age to early adolescence. DESIGN, SETTING, AND PARTICIPANTS: Data were collected in an academic research setting from September 22, 2003, to December 13, 2014, on 193 children aged 3 to 6 years from the St Louis, Missouri, metropolitan area who were observed for up to 11 years in a longitudinal behavioral and neuroimaging study of childhood depression. Multilevel modeling was applied to explore the association between the number of childhood depression symptoms and prior diagnosis of major depressive disorder and the trajectory of gray matter change across 3 scan waves. Data analysis was conducted from October 29, 2014, to September 28, 2015. MAIN OUTCOMES AND MEASURES: Volume, thickness, and surface area of cortical gray matter measured using structural magnetic resonance imaging at 3 scan waves. RESULTS: Of the 193 children, 90 had a diagnosis of major depressive disorder; 116 children had 3 full waves of neuroimaging scans. Findings demonstrated marked alterations in cortical gray matter volume loss (slope estimate, -0.93 cm3; 95% CI, -1.75 to -0.10 cm3 per scan wave) and thinning (slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave) associated with experiencing an episode of major depressive disorder before the first magnetic resonance imaging scan. In contrast, no significant associations were found between development of gray matter and family history of depression or experiences of traumatic or stressful life events during this period. CONCLUSIONS AND RELEVANCE: This study demonstrates an association between early childhood depression and the trajectory of cortical gray matter development in late school age and early adolescence. These findings underscore the significance of early childhood depression on alterations in neural development. PMID- 26676836 TI - Anxiety Sensitivity, Experiential Avoidance, and Mindfulness Among Younger and Older Adults: Age Differences in Risk Factors for Anxiety Symptoms. AB - In this cross-sectional study, we examined age-related differences in anxiety sensitivity (AS), experiential avoidance (EA), and mindfulness among younger adult students (N=426; M age=20.1 years) and community-dwelling older adults (N=85; M age=71.8 years). Participants anonymously completed the Anxiety Sensitivity Index-3, Acceptance and Action Questionnaire-II, Mindful Attention Awareness Scale, Kentucky Inventory of Mindfulness Skills, Beck Anxiety Inventory, Geriatric Anxiety Scale, and State-Trait Anxiety Inventory. Independent t tests indicated that younger adults reported significantly higher levels of AS and EA, whereas older adults reported significantly higher levels of trait mindfulness. Correlational analyses demonstrated that AS and EA were significantly associated with each other and with anxiety-related symptoms. However, trait mindfulness was significantly inversely related to AS, EA, and to trait and state anxiety. To date, these three factors have yet to be examined simultaneously within the context of age differences, and the present study illuminates these differences as well as their relationships. AS, EA, and low mindfulness appear to be significant correlates for anxiety-related symptoms in younger and older adults. PMID- 26676837 TI - Aortic CT angiography dose reduction: investigation of optimal noise index and iterative algorithm strength in combination with low kV. AB - OBJECTIVE: The purpose of this study was to optimize an aorta angiographic CT protocol, by investigating the best combination of tube current modulation, iterative algorithm strength and kV reduction. MATERIALS AND METHODS: Anthropomorphic phantoms of three sizes were imaged by CT with different values of noise index, of iterative algorithm ASIR percentages and kV in the range 80 120. Quantitative noise and contrast noise ratios were evaluated at different phantom locations. Three radiologists assessed the subjective image quality by comparing the image series with the one acquired with the reference protocol (120 kV, slice thickness 0.625, noise index 28, ASIR 40 %). RESULTS: Although the highest CNR values were obtained for the 80 kV acquisitions, qualitative scores were higher for 100 and 120 kV at the same noise index. An optimized protocol was established with a NI of 39.2, ASIR 60%, 100 kV for small- and medium-sized patients and 120 kV for large-sized patients, with a dose reduction of 47%. CONCLUSION: When different dose reduction parameters are available, anthropomorphic phantoms of different sizes help to find the optimal combination. For aorta studies, 100 kV with relative high values of noise indexes and iterative levels provides the best balance between dose reduction and image quality. PMID- 26676838 TI - Indications and efficacy of O2-O3 intradiscal versus steroid intraforaminal injection in different types of disco vertebral pathologies: a prospective randomized double-blind trial with 517 patients. AB - OBJECTIVE: The aim of this study was to prospectively evaluate the clinical efficacy of perigangliar steroid and local anesthetic with intradiscal O2-O3 injection versus steroid and local anesthetic intraforaminal injection in different types of herniation and grade of disc degeneration. MATERIALS AND METHODS: A total of 517 patients were randomly assigned to two groups. Control Group (159 men, 101 women; age range 25-89 years) underwent steroid and local anesthetic intraforaminal injection. Study Group (163 men, 94 women; age range 22 92 years) underwent the same treatment with addiction of O2-O3 intradiscal injection. Procedures were performed under computed tomographic guidance. Visual Analog Scale Questionnaire was administered before treatment and at intervals, the last at 6-month follow-up. Results were compared with Kruskal-Wallis and t test. RESULTS: After 6 months, O2-O3 discolysis was successful in 106 (41.24 %) Study Group patients with extrusions compared with 9 Control Group patients (3.5 %) (P < 0.001). In 89 (34.6 %) Study Group patients with protrusions, success rate was statistically significant compared with 5 Control Group patients (1.9 %). Significant difference was detected in the presence of Grade I, II, III of Degenerated Disc in 185 of Study Group patients (68.4 %) compared with 4 Control Group patients (1.5 %). CONCLUSIONS: The addition of O2-O3 discolysis is more effective at 6 months than perigangliar steroid and local anesthetic injection, especially in cases of herniated or protruded discs and with a Grade of Disc Degeneration from mild to moderate range. PMID- 26676839 TI - Fracture Repair in the Distal Radius in Postmenopausal Women: A Follow-Up 2 Years Postfracture Using HRpQCT. AB - Fracture healing is characterized by an intense increase in modeling and remodeling of bone, which allows removal of the cast after a stable distal radius fracture within 3 to 5 weeks. However, at that time, bone strength has not recovered yet. We studied the changes in bone mineral density (BMD), microarchitecture, and bone stiffness after a distal radius fracture during a 2 year follow-up in comparison to the contralateral side and the association between the 2-year stiffness and baseline BMD, microarchitecture, and early changes in these parameters. The fractured side of 14 postmenopausal women (mean age 64 +/- 8 years) with a conservatively treated distal radius fracture was scanned by high-resolution peripheral quantitative computed tomography (HRpQCT) at 1 to 2, 3 to 4, 6 to 8, and 12 weeks and 2 years postfracture. The same region contralaterally was scanned as well at the 2-year visit. BMD, microarchitecture, and stiffness parameters were determined and the fracture side was compared with the contralateral side using a linear mixed-effect model. Spearman's correlation was used to correlate the 2-year bone stiffness with baseline BMD, microarchitecture, and early 3-month changes in these parameters. Two years postfracture, cortical and trabecular thickness and torsional and bending stiffness were significantly higher at the fractured side compared with the nonfractured side (21%, 55%, 31%, and 29%, respectively, p < 0.05), whereas BMD was similar. Two-year torsional and bending stiffness correlated significantly with baseline BMD and cortical perimeter (|rho| >= 0.63, p < 0.016) but not with early changes in bone parameters. Using HRpQCT, this study illustrates that fracture healing is not completed by the time the cast is removed. We showed that from 6 weeks to 2 years postfracture, large changes occur in BMD, microarchitecture, and biomechanical parameters at the fractured side, which were fully recovered after 2 years in comparison to the nonfractured contralateral side. Interestingly, higher 2-year torsional and bending stiffness were associated with lower BMD and higher cortical perimeter at baseline. (c) 2015 American Society for Bone and Mineral Research. PMID- 26676840 TI - Utility of epirubicin-incorporating micelles tagged with anti-tissue factor antibody clone with no anticoagulant effect. AB - Tissue factor (TF), an initiator of the extrinsic blood coagulation cascade, is overexpressed in different types of cancer. Tissue factor overexpression is also known as a poor prognostic factor in pancreatic cancer. We recently developed anti-TF antibody (clone1849)-conjugated epirubicin-incorporating micelles (NC 6300), and reported that this anti-TF1849-NC-6300 showed enhanced antitumor activity against TF-high expressed human pancreatic cancer cells, when compared with NC-6300 alone. However, clone 1849 antibody inhibited TF-associated blood coagulation activity. We studied another anti-TF antibody, clone 1859, which had no effect on blood coagulation and prepared anti-TF1859-NC-6300. In addition, to determine the optimum size of the antibody fragment to conjugate with NC-6300, three forms of the 1859 antibody (whole IgG, F[ab']2 , and Fab') were conjugated to NC-6300. The antitumor effect of each anti-TF1859-NC-6300 was studied in vitro and in vivo, using two human pancreatic cancer cell lines, BxPC3 with high expressed TF, and SUIT2 with low levels of TF. In vitro, all forms of anti-TF1859 NC-6300 showed higher cytocidal effects than NC-6300 in BxPC3, whereas this enhanced effect was not observed in SUIT2. Likewise, all forms of anti-TF1859-NC 6300 significantly suppressed tumor growth when compared to NC-6300 in the BxPC3, but not in the SUIT2, xenograft model. Among the three forms of conjugates, anti TF1859-IgG-NC-6300 had a higher antitumor tendency in TF-high expressed cells. Thus, we have confirmed an enhanced antitumor effect of anti-TF1859-NC-6300 in a TF-high expressing tumor; anti-TF1859-IgG-NC-6300 could be used to simplify the manufacturing process of the antibody-micelle conjugation for future clinical studies. PMID- 26676841 TI - Engineered silver nanoparticles are sensed at the plasma membrane and dramatically modify the physiology of Arabidopsis thaliana plants. AB - Silver nanoparticles (Ag NPs) are the world's most important nanomaterial and nanotoxicant. The aim of this study was to determine the early stages of interactions between Ag NPs and plant cells, and to investigate their physiological roles. We have shown that the addition of Ag NPs to cultivation medium, at levels above 300 mg L(-1) , inhibited Arabidopsis thaliana root elongation and leaf expansion. This also resulted in decreased photosynthetic efficiency and the extreme accumulation of Ag in tissues. Acute application of Ag NPs induced a transient elevation of [Ca(2+) ]cyt and the accumulation of reactive oxygen species (ROS; partially generated by NADPH oxidase). Whole-cell patch-clamp measurements on root cell protoplasts demonstrated that Ag NPs slightly inhibited plasma membrane K(+) efflux and Ca(2+) influx currents, or caused membrane breakdown; however, in excised outside-out patches, Ag NPs activated Gd(3+) -sensitive Ca(2+) influx channels with unitary conductance of approximately 56 pS. Bulk particles did not modify the plasma membrane currents. Tests with electron paramagnetic resonance spectroscopy showed that Ag NPs were not able to catalyse hydroxyl radical generation, but that they directly oxidized the major plant antioxidant, l-ascorbic acid. Overall, the data presented shed light on mechanisms of the impact of nanosilver on plant cells, and show that these include the induction of classical stress signalling reactions (mediated by [Ca(2+) ]cyt and ROS) and a specific effect on the plasma membrane conductance and the reduced ascorbate. PMID- 26676842 TI - Progress in Piezo-Phototronic-Effect-Enhanced Light-Emitting Diodes and Pressure Imaging. AB - Wurtzite materials exhibit both semiconductor and piezoelectric properties under strains due to the non-central symmetric crystal structures. The three-way coupling of semiconductor properties, piezoelectric polarization and optical excitation in ZnO, GaN, CdS and other piezoelectric semiconductors leads to the emerging field of piezo-phototronics. This effect can efficiently manipulate the emission intensity of light-emitting diodes (LEDs) by utilizing the piezo polarization charges created at the junction upon straining to modulate the energy band diagrams and the optoelectronic processes, such as generation, separation, recombination and/or transport of charge carriers. Starting from fundamental physics principles, recent progress in piezo-phototronic-effect enhanced LEDs is reviewed; following their development from single-nanowire pressure-sensitive devices to high-resolution array matrices for pressure distribution mapping applications. The piezo-phototronic effect provides a promising method to enhance the light emission of LEDs based on piezoelectric semiconductors through applying static strains, and may find perspective applications in various optoelectronic devices and integrated systems. PMID- 26676843 TI - Conditions for confounding of interactions. AB - PURPOSE: Pharmaco-epidemiology increasingly investigates drug-drug or drug covariate interactions. Yet, conditions for confounding of interactions have not been elucidated. We explored the conditions under which the estimates of interactions in logistic regression are affected by confounding bias. METHODS: We rely on analytical derivations to investigate the conditions and then use simulations to confirm our analytical results and to quantify the impact of selected parameters on the bias of the interaction estimates. RESULTS: Failure to adjust for a risk factor U results in a biased estimate of the interaction between exposures E1 and E2 on a binary outcome Y if the association between U and E1 varies depending on the value of E2. The resulting confounding bias increases with increase in the following: (i) prevalence of confounder U; (ii) strength of U-Y association; and (iii) heterogeneity in the association of E1 with U across the strata of E2. A variable that is not a confounder for the main effects of E1 and E2 may still act as an important confounder for their interaction. CONCLUSIONS: Studies of interactions should attempt to identify-as potential confounders-those risk factors whose associations with one of the exposures in the interaction term may be modified by the other exposure. PMID- 26676844 TI - FAM172A modulates apoptosis and proliferation of colon cancer cells via STAT1 binding to its promoter. AB - In our previous study, low expression of FAM172A protein was found in colon cancer tissues. This research was planned to explore the functions of FAM172A gene and examine the mechanisms of its transcriptional regulation. Firstly, flow cytometry showed that FAM172A inhibited proliferation and promoted apoptosis and differentiation of colon cancer cells. Then through continuous truncation, we identified the minimal functional promoter region of FAM172A. Subsequently, we found that STAT1, as a transcription factor, could bind to the minimal FAM172A promoter, as evaluated using Chromatin immunoprecipitation (ChIP) and Electrophoreticmobility shift assay (EMSA). The results of Western blot analysis and qRT-PCR indicated that STAT1 was able to upregulate the expression of FAM172A. Our results showed that FAM172A could suppress proliferation of colon cancer cells, and STAT1 could bind to the minimum promoter region of FAM172A and upregulated the expression of FAM172A. These results may provide advanced insights into the functions of FAM172A and its regulatory mechanisms. PMID- 26676845 TI - Native LDL promotes differentiation of human monocytes to macrophages with an inflammatory phenotype. AB - Recruitment of monocytes in atherosclerosis is dependent upon increased levels of plasma lipoproteins which accumulate in the blood vessel wall. The extracellular milieu can influence the phenotype of monocyte subsets (classical: CD14++CD16-, intermediate: CD14+CD16+ and non-classical: CD14dimCD16++) and macrophages (M1 or M2) and consequently the initiation, progression and/or regression of atherosclerosis. However, it is not known what effect lipoproteins, in particular native low-density lipoproteins (nLDL), have on the polarisation of monocyte derived macrophages. Monocytes were differentiated into macrophages in the presence of nLDL. nLDL increased gene expression of the inflammatory cytokines TNFalpha and IL-6 in macrophages polarised towards the M1 phenotype while decreasing the M2 surface markers, CD206 and CD200R and the anti-inflammatory cytokines TGFbeta and IL-10. Compared to the classical and intermediate subsets, the non-classical subset-derived macrophages had a reduced ability to respond to M1 stimuli (LPS and IFNgamma). nLDL enhanced the TNFalpha and IL-6 gene expression in macrophages from all monocyte subsets, indicating an inflammatory effect of nLDL. Further, the classical and intermediate subsets both responded to M2 stimuli (IL-4) with upregulation of TGFbeta and SR-B1 mRNA; an effect, which was reduced by nLDL. In contrast, the non-classical subset failed to respond to IL-4 or nLDL, suggesting it may be unable to polarise into M2 macrophages. Our data suggests that monocyte interaction with nLDL significantly affects macrophage polarisation and that this interaction appears to be subset dependent. PMID- 26676846 TI - NIR bacteriochlorin chromophores accessed by Heck and Sonogashira cross-coupling reactions on a tetrabromobacteriochlorin derivative. AB - The synthesis of a new tetrabromobacteriochlorin BCBr4 is reported having the 3,4 dibromo-1H-pyrrole-2-carbaldehyde (10) as the major precursor. The BCBr4 was successfully employed in Pd cross-coupling reactions with methyl acrylate, phenyl acetylene and 4-ethynylanisole. In all three cases, the desired tetra-coupled products were obtained in good to excellent yields, and present a significant red shift in the UV-Vis bands above 800 nm. DFT and TD-DFT theoretical analyses of the NIR bacteriochlorin chromophores were performed in order to evaluate the effect of beta substitution on their electronic structures. PMID- 26676847 TI - Eczema Trials: Quality of Life Instruments Used and Their Relation to Patient reported Outcomes. A Systematic Review. AB - It is unclear which quality of life instruments have thus far been used in eczema trials. Therefore, we aimed to identify these instruments. We searched the Global Resource of Eczema Trials (GREAT) database for reports of randomized controlled trials. Information on patient-reported outcomes, particularly quality of life, was extracted from eligible studies. 287 full texts reporting on 303 trials and 72 abstracts were included. 63/303 studies (20.8%) assessed quality of life and used 18 named and 4 unnamed instruments. The Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI), the Infant's Dermatitis Quality of Life Index (IDQOL), and the Dermatitis Family Impact (DFI) were the most common measures in adults, children, infants, and caregivers, respectively. In conclusion, only about one fifth of eczema trials include a quality of life measure as outcome. Many different instruments are used, limiting the possibilities of comparing and synthesising individual trials' findings. PMID- 26676848 TI - CME stands for commercial medical education: and ACCME still won't address the issue. PMID- 26676849 TI - Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma. AB - Long non-coding RNA (lncRNA) is a variety of the human transcriptome that does not code for proteins and plays an important role in the development and progression of multiple solid malignant tumors. However, the roles of lncRNAs in the development of pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, we investigated the expression patterns of lncRNAs in three PDAC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via a microarray with 30,586 lncRNA probes and 26,109 mRNA probes. The lncRNA microarray revealed 27,279 lncRNAs in PDAC samples, of which 2,331 were significantly upregulated (P<0.05; T/N>2.0) and 1,641 were downregulated (P<0.05; N/T>2.0) compared with matched adjacent non-tumor samples. In addition, 19,995 mRNAs were detected, of which 1,676 were significantly upregulated (P<0.05; T/N>2.0) and 1,981 were downregulated (P<0.05; N/T>2.0). Pathway analysis indicated that 41 pathways corresponded to upregulated transcripts and 25 pathways corresponded to downregulated transcripts (P-value cut-off is 0.05). Gene ontology (GO) analysis showed that the highest enriched GOs targeted by upregulated and downregulated transcripts were tissue homeostasis. The validation results from quantitative reverse transcription polymerase chain reaction (qRT PCR) analysis and microarray analysis were consistent. Furthermore, the expression level of long intergenic non-coding RNA HOTAIRM1 was upregulated in 12 PDAC tissues samples compared with matched adjacent non-tumor samples by qRT-PCR. The results showed that the lncRNA and mRNA expression profiles differed significantly between the PDAC tissues and their adjacent non-tumor tissues, and the revelation of an association between HOTAIRM1 expression and PDAC is especially noteworthy. These findings may provide new potential molecular markers for diagnosis and treatment of PDAC. PMID- 26676850 TI - Toll-like receptor 3 signalling mediates angiogenic response upon shock wave treatment of ischaemic muscle. AB - AIMS: Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate immunity, is activated by binding double-stranded (ds) RNA. It plays a key role in inflammation, a process that is needed also for angiogenesis. We hypothesize that SWT causes cellular cavitation without damaging the target cells, thus liberating cytoplasmic RNA that in turn activates TLR3. METHODS AND RESULTS: SWT induces TLR3 and IFN-beta1 gene expression as well as RNA liberation from endothelial cells in a time-dependant manner. Conditioned medium from SWT-treated HUVECs induced TLR3 signalling in reporter cells. The response was lost when the medium was treated with RNase III to abolish dsRNAs or when TLR3 was silenced using siRNAs. In a mouse hind limb ischaemia model using wt and TLR3(-/-) mice (n = 6), SWT induced angiogenesis and arteriogenesis only in wt animals. These effects were accompanied by improved blood perfusion of treated limbs. Analysis of main molecules of the TLR3 pathways confirmed TLR3 signalling in vivo following SWT. CONCLUSION: Our data reveal a central role of the innate immune system, namely Toll-like receptor 3, to mediate angiogenesis upon release of cytoplasmic RNAs by mechanotransduction of SWT. PMID- 26676851 TI - Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: protein mislocalization versus epitope masking. AB - AIMS: To examine the relevance and cause of reduced plakoglobin IF in intercalated discs for arrhythmogenic right ventricular cardiomyopathy (ARVC) and ARVC-like disease in mouse and human. METHODS AND RESULTS: Normalized semi quantitative IF measurements were performed in a standardized format in desmoglein 2-mutant mice with an ARVC-like phenotype (n = 6) and in cardiac biopsies from humans with ARVC and non-ARVC heart disease (n = 10). Reduced plakoglobin staining was detectable in ARVC only with one antibody directed against a defined epitope but not with three other antibodies reacting with different epitopes of plakoglobin. CONCLUSIONS: Reduced plakoglobin staining in intercalated discs of heart tissue from human ARVC patients and in a murine ARVC model is caused by alterations in epitope accessibility and not by protein relocalization. PMID- 26676852 TI - Prenatal Oxycodone Exposure Alters CNS Endothelin Receptor Expression in Neonatal Rats. AB - Prenatal opioid exposure such as oxycodone is linked to significant adverse effects on the developing brain. Endothelin (ET) and its receptors are involved in normal development of the central nervous system. Opioid tolerance and withdrawal are mediated through ET receptors. It is possible that adverse effect of oxycodone on the developing brain is mediated through ET receptors. We evaluated brain ETA and ETB receptor expression during postnatal development in rats with prenatal oxycodone exposure. Timed pregnant Sprague-Dawley rats received either oxycodone or placebo throughout gestation. After birth, male rat pups were sacrificed on postnatal day (PND) 1, 7, 14 or 28. Brain ETA and ETB receptor expression was determined by Western blot analysis. Oxycodone pups compared to placebo demonstrated congenital malformations of the face, mouth, and vertebrae at the time of birth [4/69 (5.7%) vs. 0/60 (0%); respectively] and intrauterine growth retardation [10/69 (15%) vs. 2/60 (3.3%); respectively]. On PND 28, oxycodone pups compared to placebo had lower body and kidney weight. ETA receptor expression in the oxycodone group was significantly higher compared to placebo on PND 1 (p=0.035), but was similar on PND 7, 14, or 28. ETB receptor expression decreased in oxycodone compared to placebo on PND 1 and 7 (p=0.001); and increased on PND 28 (p=0.002), but was similar on PND 14. Oxycodone-exposed rat pups had lower birth weight and postnatal weight gain and greater congenital malformations. ETB receptor expression is altered in the brain of oxycodone treated rat pups indicating a possible delay in CNS development. PMID- 26676853 TI - Effects of point spread function-based image reconstruction on neuroreceptor binding in positron emission tomography study with [(11)C]FLB 457. AB - The ordered subset expectation maximization with a point spread function (OSEM PSF) was developed to improve the spatial resolution of reconstructed positron emission tomography (PET) images and has been reported to improve the contrast of hot spots in PET studies for oncology. However, in neuroreceptor imaging, the regional radioactivity concentration changes dynamically during the scan, and the effects of the PSF may differ among various radioligands or quantification methods. In this study, we investigated the effects of the PSF on quantification in PET studies with [(11)C]FLB 457 of dopamine D2 receptors, using both phantom and human data acquired by the Siemens Biograph 16 imaging platform. In the phantom studies, we evaluated the hot contrast recovery coefficient (HCRC) for variously sized hot spheres and the linearity between the measured and true radioactivities in OSEM-PSF images. Next, in the human studies with [(11)C]FLB 457, radioactivity concentrations and binding potentials for the cerebral cortex and thalamus were compared between images reconstructed with and without PSF. In the phantom studies, the OSEM-PSF images showed a better HCRC compared to images without PSF, and they showed a good linear correlation with true radioactivity. In the human studies, the radioactivity concentration increased especially in small regions with high accumulation of [(11)C]FLB 457 when the PSF was included. However, little difference in the binding potentials was observed for the target regions between both types of reconstructed images. In conclusion, PSF-based reconstruction reduced the spill-over phenomena in small hot regions; however, it caused no increase in the binding potentials in the [(11)C]FLB 457 studies. PMID- 26676854 TI - Hepatocyte differentiation of human induced pluripotent stem cells is modulated by stearoyl-CoA desaturase 1 activity. AB - Stearoyl-CoA desaturase 1 (SCD1) plays important roles in organ development, glucose tolerance, insulin sensitivity, and cancer. Here, we examined the role of SCD1 for the differentiation of human induced pluripotent stem (hiPS) cells to liver cells by using drug inhibition and biochemical experiments. hiPS cells cultured in a pro-hepatic medium were exposed to an SCD1 inhibitor at various stages throughout differentiation. Liver-specific markers, specifically alpha fetoprotein, albumin and urea in conditioned medium, and hepatocyte nuclear factor 4alpha (HNF4alpha) and cytochrome P450 7A1 (CYP7A1) gene expressions and triglyceride in cellular extracts were analyzed at various development stages. Measures of hepatocyte-specific function and triglyceride accumulation in later stages were strongly inhibited a minimum of -29% (P < 0.05) by SCD1 inhibitor in the early stage of hepatic differentiation and effectively reversed (>30%, P < 0.01) by the addition of oleate. The results were also reproducible with human primary mononuclear cells (hPMN). SCD1 inhibitor had no significant effect on liver-specific markers when it was added in the hepatic maturation stage. However, it strikingly led to higher albumin (1.6-fold, P = 0.03) and urea (1.9 fold, P = 0.02) production, and HNF4alpha (1.9-fold, P = 0.02) and CYP7A1 (1.3 fold, P = 0.03) expression upon incubation during the lineage-commitment stage. Hepatic differentiation from cultured hiPS cells is sensitive to SCD1 inhibition and this sensitivity is affected by the stage of cellular differentiation. Notably, findings also indicate that this notion can be extended to hPMN. The requirement for SCD1 activity in functional differentiation of hepatocytes may have relevance for human liver disease and metabolic dysregulation. PMID- 26676855 TI - Simplified risk stratification criteria for identification of patients with MRSA bacteremia at low risk of infective endocarditis: implications for avoiding routine transesophageal echocardiography in MRSA bacteremia. AB - The aim of this study was to identify patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with low risk of infective endocarditis (IE) who might not require routine trans-esophageal echocardiography (TEE). We retrospectively evaluated 398 patients presenting with MRSA bacteremia for the presence of the following clinical criteria: intravenous drug abuse (IVDA), long term catheter, prolonged bacteremia, intra-cardiac device, prosthetic valve, hemodialysis dependency, vertebral/nonvertebral osteomyelitis, cardio-structural abnormality. IE was diagnosed using the modified Duke criteria. Of 398 patients with MRSA bacteremia, 26.4 % of cases were community-acquired, 56.3 % were health care-associated, and 17.3 % were hospital-acquired. Of the group, 44 patients had definite IE, 119 had possible IE, and 235 had a rejected diagnosis. Out of 398 patients, 231 were evaluated with transthoracic echocardiography (TTE) or TEE. All 44 patients with definite IE fulfilled at least one criterion (sensitivity 100 %). Finally, a receiver operator characteristic (ROC) curve was obtained to evaluate the total risk score of our proposed criteria as a predictor of the presence of IE, and this was compared to the ROC curve of a previously proposed criteria. The area under the ROC curve for our criteria was 0.710, while the area under the ROC curve for the criteria previously proposed was 0.537 (p < 0.001). The p-value for comparing those 2 areas was less than 0.001, indicating statistical significance. Patients with MRSA bacteremia without any of our proposed clinical criteria have very low risk of developing IE and may not require routine TEE. PMID- 26676856 TI - Anti-Toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants. AB - Intraocular delivery systems have been developed to treat many eye diseases, especially those affecting the posterior segment of the eye. However, ocular toxoplasmosis, the leading cause of infectious posterior uveitis in the world, still lacks an effective treatment. Therefore, our group developed an intravitreal polymeric implant to release clindamycin, a potent anti-Toxoplasma antibiotic. In this work, we used different techniques such as differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy, and fourier-transform infrared spectroscopy to investigate drug/polymer properties while manufacturing the delivery system. We showed that the lyophilization, hot molding process, and sterilization by gamma irradiation did not change drug/polymer physical-chemistry properties. The drug was found to be homogeneously dispersed into the poly lactic-co-glycolic acid (PLGA) chains and the profile release was characterized by an initial burst followed by prolonged release. The drug profile release was not modified after gamma irradiation and non-covalent interaction was found between the drug and the PLGA. We also observed the preservation of the drug activity by showing the potent anti Toxoplasma effect of the implant, after 24-72 h in contact with cells infected by the parasite, which highlights this system as an alternative to treat toxoplasmic retinochoroiditis. PMID- 26676857 TI - Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering. AB - Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 +/- 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 +/- 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 +/- 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue engineered should be developed for effective cartilage replacements for nasal reconstruction. PMID- 26676858 TI - Combined delivery of PDGF-BB and BMP-6 for enhanced osteoblastic differentiation. AB - Natural microenvironment during bone tissue regeneration involves integration of multiple biological growth factors which regulate mitogenic activities and differentiation to induce bone repair. Among them platelet derived growth factor (PDGF-BB) and bone morphogenic protein-6 (BMP-6) are known to play a prominent role. The aim of this study was to investigate the benefits of combined delivery of PDGF-BB and BMP-6 on proliferation and osteoblastic differentiation of MC3T3 E1 preosteoblastic cells. PDGF-BB and BMP-6 were loaded in gelatin and poly (3 hydroxybutyric acid-co-3-hydroxyvaleric acid) particles, respectively. The carrier particles were then loaded into 3D chitosan matrix fabricated by freeze drying. The fast release of PDGF-BB during 7 days was accompanied by slower and prolonged release of BMP-6. The premising release of mitogenic factor PDGF-BB resulted in an increased MC3T3-E1 cell population seeded on chitosan scaffolds. Osteogenic markers of RunX2, Col 1, OPN were higher on chitosan scaffolds loaded with growth factors either individually or in combination. However, OCN expression and bone mineral formation were prominent on chitosan scaffolds incorporating PDGF-BB and BMP-6 as a combination. PMID- 26676860 TI - Optimisation of UV irradiation as a binding site conserving method for crosslinking collagen-based scaffolds. AB - Short wavelength (lambda = 254 nm) UV irradiation was evaluated over a range of intensities (0.06 to 0.96 J/cm(2)) as a means of cross-linking collagen- and gelatin-based scaffolds, to tailor their material characteristics whilst retaining biological functionality. Zero-link carbodiimide treatments are commonly applied to collagen-based materials, forming cross-links from carboxylate anions (for example the acidic E of GFOGER) that are an essential part of integrin binding sites on collagen. Cross-linking these amino acids therefore disrupts the bioactivity of collagen. In contrast, UV irradiation forms bonds from less important aromatic tyrosine and phenylalanine residues. We therefore hypothesised that UV cross-linking would not compromise collagen cell reactivity. Here, highly porous (~99 %) isotropic, collagen-based scaffolds were produced via ice-templating. A series of scaffolds (pore diameters ranging from 130-260 MUm) with ascending stability in water was made from gelatin, two different sources of collagen I, or blends of these materials. Glucose, known to aid UV crosslinking of collagen, was added to some lower-stability formulations. These scaffolds were exposed to different doses of UV irradiation, and the scaffold morphology, dissolution stability in water, resistance to compression and cell reactivity was assessed. Stabilisation in aqueous media varied with both the nature of the collagen-based material employed and the UV intensity. Scaffolds made from the most stable materials showed the greatest stability after irradiation, although the levels of cross-linking in all cases were relatively low. Scaffolds made from pure collagen from the two different sources showed different optimum levels of irradiation, suggesting altered balance between stabilisation from cross-linking and destabilisation from denaturation. The introduction of glucose into the scaffold enhanced the efficacy of UV cross linking. Finally, as hypothesized, cell attachment, spreading and proliferation on collagen materials were unaffected by UV cross-linking. UV irradiation may therefore be used to provide relatively low level cross-linking of collagen without loss of biological functionality. PMID- 26676859 TI - DC BeadM1TM: towards an optimal transcatheter hepatic tumour therapy. AB - Clinical use of DC BeadTM loaded with doxorubicin (DEBDOXTM) or irinotecan (DEBIRITM), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 MUm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100-300 um beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 um compared to 100-300 um beads. Radiopaque versions of 70-150 and 100 300 um beads were prepared in order to evaluate distribution ex vivo using u-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70-150 MUm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100-300 um beads. PMID- 26676861 TI - Investigation of structural collapse in unidirectionally freeze cast collagen scaffolds. AB - Though unidirectional freeze casting is a facile method for the production of structurally anisotropic biomedical scaffolds, challenges exist in optimizing the drying process that are often overlooked. In particular, structural collapse may occur if the material's frozen-state glass transition temperature (Tg') is exceeded. It was discovered that unidirectionally freeze cast collagen matrices were highly deformed following lyophilization, rendering them incapable of further use. In this study, modulated differential scanning calorimetry was performed to identify Tg's of unidirectionally freeze cast collagen scaffolds, and product temperatures during sublimation were recorded. It was observed that cast matrices from 0.5 to 0.05 M acetic acid (HAc) sublimed at a lyophilizer shelf temperature of -25 degrees C underwent structural collapse and exceeded their Tg's for the majority of the drying cycle. The use of a low pH suspension (0.5 M HAc) promoted the formation of a non-porous surface, which in turn contributed to the increase of the product temperature above its Tg' during drying. This study has revealed that use of a low shelf temperature (-40 degrees C) and a low HAc concentration (0.05 M) is effective in maintaining product temperatures under Tg' thereby preventing collapse in unidirectionally freeze cast collagen scaffolds. PMID- 26676862 TI - Substantivity of Ag-Ca-Si mesoporous nanoparticles on dentin and its ability to inhibit Enterococcus faecalis. AB - The main purpose of this study was to investigate the substantivity of Ag-Ca-Si mesoporous nanoparticles (Ag-MCSNs) on dentin and its residual antibacterial effects against Enterococcus faecalis. Ag-MCSNs were fabricated and characterized, ion release profile and pH were tested, and the ability to inhibit planktonic E. faecalis as well as the cytotoxicity was evaluated. Dentin slices were medicated with Ca(OH)2 paste, 2 % chlorhexidine gel and Ag-MCSNs paste for 7 days and then irrigated. Dentin slices were then immersed in E. faecalis suspension for 6 days and then transferred to fresh brain heart infusion solution. The optical density value within 10 h after immersing and transferring were measured and compared among groups. Results indicated that Ag-MCSNs showed high pH, sustained Ag(+)-Ca(2+)-SiO3 (2-) ion release, and high substantivity on dentin. The Ag-MCSNs exhibited strong antibacterial effects against planktonic E. faecalis and much better residual inhibition effects against E. faecalis growth on dentin than Ca(OH)2 paste (P < 0.05). The Ag-MCSNs showed excellent antibacterial ability against E. faecalis and high substantivity on dentin, which might be developed to a new effective intra-canal medicament for human teeth. PMID- 26676863 TI - Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery. AB - Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency. PMID- 26676864 TI - Antibacterial properties of poly (octanediol citrate)/gallium-containing bioglass composite scaffolds. AB - Bioactive glasses may function as antimicrobial delivery systems through the incorporation and subsequent release of therapeutic ions. The aim of this study was to evaluate the antimicrobial properties of a series of composite scaffolds composed of poly(octanediol citrate) with increased loads of a bioactive glass that releases zinc (Zn(2+)) and gallium (Ga(3+)) ions in a controlled manner. The antibacterial activity of these scaffolds was investigated against both Gram positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive glass exhibited antibacterial activity and this increased in vitro with higher bioactive glass loads; viable cells decreased to about 20 % for the composite scaffold containing 30 % bioactive glass. The Ga(3+) release rate increased as a function of time and Zn(2+) was shown to incorporate into the surrounding bone. PMID- 26676865 TI - Chondrogenic effect of cell-based scaffold of self-assembling peptides/PLGA-PLL loading the hTGFbeta3 plasmid DNA. AB - With the application of tissue engineering to tissue regeneration, additional new complexes have been made in response to the challenge of cartilage-injury repair. This study was performed to construct a rat precartilaginous stem cells-based scaffold of self-assembling peptides RADA16-I/PLGA-PLL (poly-L-lysine coated PLGA) as extracellular matrix loading the NLS-TAT as a peptide-based carrier for a plasmid DNA containing hTGFbeta3. After composites were cultured for 1, 2, 3 and 4 weeks, respectively, the results showed that the levels of chondrogenic related gene expression were higher in the experimental group with and hTGFbeta3 gene by reverse transcription-polymerase chain reaction, and with higher histochemical and immunohistochemical expression. hTGFbeta3 protein expression had increased at 4 weeks based on western blot analysis. The results of this study show that a complex may be a suitable scaffold for cartilage repair and offer a strategy for tissue regeneration through the use of tissue engineering. PMID- 26676866 TI - Does this ventilated patient have asynchronies? Recognizing reverse triggering and entrainment at the bedside. PMID- 26676867 TI - Reduced proliferation and increased apoptosis of the SGC-7901 gastric cancer cell line on exposure to GDC-0449. AB - The sonic hedgehog (Shh) pathway is known to be vital in embryonic development and cancer propagation due to its irreplaceable role in cell proliferation and differentiation. GDC-0449, a basal cell skin cancer target drug approved by the Food and Drugs Administration, is a smoothened (Smo)-specific antagonist. Although it has been clinically verified as a valid drug for the treatment of skin and pancreatic cancer, the application of GDC-0449 in gastric cancer requires further investigation. In the present study, high-glucose Dulbecco's modified Eagle's medium with 10% fetal bovine serum was used for routine SGC-7901 cell line culture. A Cell Counting Kit-8 assay was employed for determination of the reproductive rate of the cells. Flow cytometry was performed to determine the apoptosis status of the SGC-7901 cell line through Q4 analysis. Reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used as target molecule detection vehicles. As expected, GDC-0449 reduced the expression levels of Shh-associated molecules, including Smo and gli1, compared with the blank group. The rate of cell proliferation was markedly limited and was accompanied by an increase in the apoptotic rate following GDC 0449 exposure. In addition, further investigations confirmed B cell lymphoma-2 (Bcl-2) as the downstream molecular mechanism of GDC-0449 efficacy. Of note, representatives of the cancer stem cell (CSC) surface marker, CD44 and CD133, demonstrated a similar trend to the Smo restriction observed. By repressing the expression of Bcl-2, GDC-0449 inhibited the normal proliferation of SGC-7901 cells, and accelerated the apoptotic rate of the cells. It may also alter CSC properties due to the reduction in the expression of surface markers. PMID- 26676868 TI - Oregano (Lippia graveolens) essential oil added within pectin edible coatings prevents fungal decay and increases the antioxidant capacity of treated tomatoes. AB - BACKGROUND: Tomato is a fruit widely consumed due to its flavor and nutritional value; however, it is susceptible to fungi contamination. Oregano essential oil (OEO) is a fungicide whose constituents are volatile; therefore, their incorporation within edible coatings can protect them and maintain their efficacy. In this context, this study evaluated the effect of OEO applied within pectin coatings on the inhibition of Alternaria alternata growth, antioxidant content and sensorial acceptability of tomatoes. RESULTS: The major volatile compounds of OEO were carvacrol (47.41%), p-cymene (26.44%) and thymol (3.02%). All the applied OEO concentrations (15.7, 25.9 and 36.1 g L(-1) ) inhibited the in vitro growth of A. alternata, whereas the in vivo effective concentrations were 25.9 and 36.1 g L(-1) . Additionally, there was an increment of total phenols and antioxidant activity in coated tomatoes compared to controls. Aroma acceptability of tomatoes was not affected by the pectin-OEO coating; additionally, the pectin, pectin-OEO 15.7 g L(-1) treatments and control tomatoes showed higher flavor acceptability than those coated with pectin-OEO 25.9 and 36.1 g L(-1) . CONCLUSION: Pectin-OEO coatings showed antifungal effect and increased the antioxidant activity without negative effects on the sensorial acceptability of tomatoes. (c) 2015 Society of Chemical Industry. PMID- 26676869 TI - No need for a social cue! A masked magician can also trick the audience in the vanishing ball illusion. AB - In the vanishing ball illusion (VBI), a magician throws a ball up in the air twice, after which he pretends to toss it up again, when in fact it remains secretly concealed in his hand. Observers perceive an imaginary ball disappearing into the air. According to Kuhn and Land (2006), the VBI during the fake throw is mediated by the magician's gaze and/or head direction (also called "social cues") as he looks toward the imaginary ball. The aim of this article is to test an alternative interpretation. According to our hypothesis, the magician's social cues are not essential to the VBI. We compared the numbers of participants experiencing the VBI when the magician's social cues were directed toward the illusory ball and when the magician's social cues were either hidden behind a black mask (Exp. 1) or stationary (Exp. 2). The results showed that the number of observers experiencing the VBI was high (almost two-thirds of the participants), regardless of whether the magician's social cueing was directed toward the illusion, hidden behind a mask, or stationary. In a third experiment (Exp. 3), we replicated Kuhn and Land's initial results and attempted to further explain their "anti-illusion" social-cue effect. This study confirms that social cueing is not required in the VBI: Its presence did not increase the number of participants experiencing the illusion. PMID- 26676870 TI - Pulling out all the stops to make the distance: Effects of effort and optical information in distance perception responses made by rope pulling. AB - Human observers perceive distance in remarkably stable and consistent manner across response methods and experimental paradigms. Most empirical work on the problem focused exclusively on geometrical variables, such as angle of declination below the horizon (Ooi, Wu, & He, 2001), with more recent considerations of nonvisual factors, such as effort (Proffitt, 2006). Hajnal, Bunch, and Kelty-Stephen (2014) showed that in addition to the object's physical angle of declination below the horizon, nonvisual variables related to effort were utilized when making distance estimates to objects placed on a sloped ramp. In that experiment, the horizontal ground surface was visible in the background when viewing objects placed on the sloped surface. To further investigate the joint utility of geometric and effort-based variables, we tested the effect of both classes of predictors on a natural hillside where a flat, horizontal surface was not visible in the background. This setup allowed us to evaluate whether observers rely on the same information to perceive distance on ramps versus real hills. The present research implicates the hypothesis that perceived effort and the geometry of space determine distance perception through interactions across multiple temporal scales of perceptual competence. PMID- 26676871 TI - Exploring handedness asymmetries in the Simon effect. AB - Spatially corresponding stimulus-response pairings usually produce shorter reaction times (RTs) than do non-corresponding pairings, even when the spatial dimension of the stimulus is irrelevant to the task. This "Simon effect" for visual stimuli and manual responses is often larger for the stimulus location on the side to which the person's dominant hand is operating. The present study aimed at replicating and examining the nature of this asymmetry. To determine whether the Simon effect asymmetry is a function of the hand distinction or of conceptual spatial codes, performance with left and right manual key-presses was compared to that with vocal responses "left" and "right." Whether the asymmetric Simon effect pattern is restricted to spatial stimuli was tested by comparing effects obtained with left and right located squares to those found with the centered words Left and Right. The asymmetry was only replicated for the spatial stimulus-manual response Simon task, for which a second experiment showed similar results when the hands and response box were not visible during task performance. The analysis revealed a general dominant-hand RT advantage that similarly adds to both corresponding and non-corresponding trials and is rather independent from the Simon effect. This advantage yields an apparent asymmetry when the data are analyzed as a function of correspondence for each stimulus location because the corresponding and non-corresponding RTs that are compared come from different hands. PMID- 26676872 TI - Components of reward-driven attentional capture. AB - Recent research reported that task-irrelevant colors captured attention if these colors previously served as search targets and received high monetary reward. We showed that both monetary reward and value-independent mechanisms influenced selective attention. Participants searched for two potential target colors among distractor colors in the training phase. Subsequently, they searched for a shape singleton in a testing phase. Experiment 1 found that participants were slower in the testing phase if a distractor of a previous target color was present rather than absent. Such slowing was observed even when no monetary reward was used during training. Experiment 2 associated monetary rewards with the target colors during the training phase. Participants were faster finding the target associated with higher monetary reward. However, reward training did not yield value dependent attentional capture in the testing phase. Attentional capture by the previous target colors was not significantly greater for the previously high reward color than the previously low or no-reward color. These findings revealed both the power and limitations of monetary reward on attention. Although monetary reward can increase attentional priority for the high-reward target during training, subsequent attentional capture effects may not be reward-based, but reflect, in part, attentional capture by previous targets. PMID- 26676873 TI - Intratemporal facial nerve schwannoma: clinical presentation and management. AB - Facial nerve schwannoma is the most common facial nerve tumor, but its therapeutic strategy remains debated. The aim of this study is to analyze the facial nerve function and the hearing outcomes after surgery or wait-and-scan policy in a facial nerve schwannoma series. A monocentric retrospective review of medical charts of patients followed for an intratemporal facial nerve schwannoma between 1988 and 2013 was performed. Twenty-two patients were included. Data were extracted pertaining to the following variables: patient demographics, tumor localization, clinical and imaging features, facial nerve function and hearing levels, and details of surgical intervention. The majority of tumors were located at the geniculate ganglion. Initial symptoms were mainly facial palsy and hearing loss. The average follow-up was 4.8 +/- 4.5 years. Nineteen patients underwent surgery, and three patients were observed. After surgery, 11 patients had a stable or improved facial nerve function (57.9 %), and 8 patients had a worsened facial nerve function (42.1 %). Facial nerve function was in the majority of cases a HB grade III, depending on surgical strategy. No patient presented a postoperative HB grade V or VI. Regarding the hearing, it remained stable after surgery in 52.6 % of cases, and improved in 10.5 % of cases. Among monitored patients, facial nerve function and hearing remained stable. Surgery for facial nerve schwannoma is a safe and effective option in the treatment of these tumors. PMID- 26676874 TI - Is age a limiting factor for adaptation to cochlear implant? AB - The influence of age on adaptation to cochlear implant (CI) is still being contested in the literature. The aim of this study was twofold. First, hearing outcomes in quiet conditions were compared between CI users implanted over and under the age of 70 years. Second, the effect of the duration of auditory deprivation was investigated. The study design is a retrospective review and the setting is in academic tertiary referral center. One hundred and twenty-one postlingually deafened implanted adults participated in this study. Hearing outcomes were compared between 121 postlingually deafened adults implanted under 40, between 40 and 70, and over 70 years of age. Speech audiometry measurements were taken at 1, 3, 6, 12, 24 and 60 months post-cochlear implantation (pCI), in quiet conditions only. Hearing outcomes were significantly better only at 1 year pCI in the youngest group compared to the two older groups. No significant difference was observed between the middle-aged and eldest subjects at any time. The influence of the severe-to-profound hearing loss (SPHL) duration was investigated and found to be equally distributed among the different age groups. Good hearing outcomes in elderly patients are not secondary to a difference in SPHL duration. Age should not be a limiting factor for cochlear implantation decision. PMID- 26676875 TI - Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis. AB - A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments. PMID- 26676876 TI - Preferences of lung cancer patients for treatment and decision-making: a systematic literature review. AB - The consideration of patient preferences in decision-making has become more important, especially for life-threatening diseases such as lung cancer. This paper aims to identify the preferences of lung cancer patients with regard to their treatment and involvement in the decision-making process. We conducted a systematic literature review from 12 electronic databases and included studies published between 2000 and 2012. A total of 20 studies were included in this review. These revealed that lung cancer patients do have preferences that should be considered in treatment decisions; however, these preferences are not homogenous. We found that patients often consider life extension to be more important than the health-related quality of life or undesirable side effects. This preference seems to depend on patient age. Nausea and vomiting are the most important side effects to be avoided; the relevance of other side effects differs highly between subgroups. The majority of lung cancer patients, nevertheless, seem to prefer a passive rather than an active role in decision-making, although the self-reported preferences differed partly from the physicians' perceptions. Overall, we identified an urgent need for larger studies that are suitable for subgroup analyses and incorporate multi-attributive measurement techniques. PMID- 26676877 TI - Feasibility and safety of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system: comparison with a 4-French catheter system. AB - PURPOSE: To assess the technical feasibility of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system (3-Fr). MATERIALS AND METHODS: Sixty-two patients with head and neck cancer who underwent transfemoral intra-arterial chemotherapy were included in this study. Thirty three patients underwent treatment using a 3-Fr (group 3-Fr). Twenty-nine patients underwent treatment using a 4-French catheter system (group 4-Fr). The technical success rate, duration of the procedure with fluoroscopy, and rate of procedure-related complications were compared between group 3-Fr and group 4-Fr. In addition, in group 3-Fr, bleeding at the puncture site after 1.5 h of bed rest was evaluated. RESULTS: The technical success rate was 100% in both groups. The duration of the procedure with fluoroscopy didn't differ between group 3-Fr (mean 28.0 min) and group 4-Fr (mean 30.2 min) (p = 0.524). There was no procedure related complication in either group. In group 3-Fr, no hemorrhagic complication was observed. CONCLUSION: A 3-French catheter system can be used to perform transfemoral intra-arterial chemotherapy for head and neck cancer and is technically feasible with approximately the same duration of the procedure with fluoroscopy. Furthermore, this method may shorten the bed rest time without hemorrhagic complication, and may reduce the risk of pulmonary embolism. PMID- 26676878 TI - Mortality After Atypical Femoral Fractures: A Cohort Study. AB - Although osteoporotic fracture rates can be reduced by bisphosphonates, prolonged therapy is associated with higher risk of atypical femoral fractures. Ordinary fragility fractures are linked to high mortality rates. We aimed to determine whether atypical femoral fractures also confer excess mortality. Radiographs were reviewed for all patients aged >=55 years who had experienced a subtrochanteric or femoral shaft fracture in Sweden in 2008 to 2010. The fractures were classified as either atypical or ordinary. Data on medication use, coexisting conditions, and date of death were obtained from national registers. We estimated multivariable-adjusted relative risks of death after atypical femoral fractures compared with ordinary subtrochanteric or femoral shaft fractures and calculated age- and sex-standardized mortality ratios (SMRs) for atypical and ordinary fractures compared with the population average. During a mean of 4 years of follow-up, 39 of 172 (23%) patients with an atypical fracture had died compared with 588 of 952 (62%) with an ordinary fracture, corresponding to a relative risk of 0.51 (95% confidence interval [CI] 0.38-0.68). The lower risk was evident in both users and nonusers of bisphosphonates. No patient with atypical fracture died in the first year after fracture. Individuals with an ordinary fracture had a higher mortality risk than the general population (SMR = 1.82; 95% CI 1.69 1.99), but no excess risk was found in patients with atypical fracture (SMR = 0.92; 95% CI 0.65-1.26). We conclude that in contrast to ordinary subtrochanteric and femoral shaft fractures, atypical femoral fractures are not associated with excess mortality. PMID- 26676879 TI - Why Psychiatry Needs Data Science and Data Science Needs Psychiatry: Connecting With Technology. PMID- 26676880 TI - Visualizing Under-Coordinated Surface Atoms on 3D Nanoporous Gold Catalysts. AB - The intricate 3D geometric shape and surface atomic structure of nanoporous gold catalysts are investigated using aberration-corrected scanning transmission electron microscopy in combination with discrete tomography. The real-space 3D atomic configurations illustrate geometrically necessary surface defects on the curved surface of the NPG, offering atomic insights into the catalysis of the nanoporous catalyst. PMID- 26676881 TI - The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals: a simulation study. AB - BACKGROUND AND OBJECTIVE: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems. METHODS: We used data simulations to explore the effect of exposure misclassification. We simulated an active substance-specific subset of a spontaneous reporting system and used the proportional reporting ratio for signal detection. The effect of exposure misclassification was evaluated in three test cases representing product-specific ADRs that may occur for biologicals and studied in relative terms by varying the model parameters (market share and relative risk). RESULTS: We found that exposure misclassification results in the largest delay in identification of risks that have a weak association (relative risk < 2 or 3) with the product of interest and in situations where the product associated with the unique risk has a large (>50%) market share. The absolute public health impact of exposure misclassification, in terms of cases/time to detection, varied considerably across the test cases. CONCLUSION: Exposure misclassification in ADR reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures. PMID- 26676882 TI - Ocoxin(r) oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice. AB - Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin(r) oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intra splenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNgamma, IL1beta, IL6 and TNFalpha were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer. PMID- 26676884 TI - Antithrombin: anti-inflammatory properties and clinical applications. AB - Many humoral and cellular components participate in bidirectional communication between the coagulation and inflammation pathways. Natural anticoagulant proteins, including antithrombin (AT), tissue factor pathway inhibitor, and protein C, suppress proinflammatory mediators. Conversely, inflammation blunts anticoagulant activity and, when uncontrolled, promotes systemic inflammation induced coagulation, such as those that occur in disseminated intravascular coagulation and severe sepsis. This review discusses the mechanisms of action and clinical use of AT concentrate in critically ill patients and in the settings of perioperative anticoagulation management for surgery and obstetrics. AT is a serine protease inhibitor with broad anticoagulant activity and potent anti inflammatory properties. In clinical conditions associated with hereditary or acquired AT deficiency, administration of AT concentrate has been shown to restore proper haemostasis and attenuate inflammation. Of note, AT modulates inflammatory responses not only by inhibiting thrombin and other clotting factors that induce cytokine activity and leukocyte-endothelial cell interaction, but also by coagulation-independent effects, including direct interaction with cellular mediators of inflammation. An increasing body of evidence suggests that AT concentrate may be a potential therapeutic agent in certain clinical settings associated with inflammation. In addition to the well-known anticoagulation properties of AT for the treatment of hereditary AT deficiency, AT also possesses noteworthy anti-inflammatory properties that could be valuable in treating acquired AT deficiency, which often result in thrombotic states associated with an inflammatory component. PMID- 26676885 TI - A 3D porous Ni-Cu alloy film for high-performance hydrazine electrooxidation. AB - Structural design and catalyst screening are two most important factors for achieving exceptional electrocatalytic performance. Herein we demonstrate that constructing a three-dimensional (3D) porous Ni-Cu alloy film is greatly beneficial for improving the hydrazine oxidation reaction (HzOR) performance. A facile electrodeposition process is employed to synthesize a Ni-Cu alloy film with a 3D hierarchical porous structure. As an integrated electrode for HzOR, the Ni-Cu alloy film exhibits superior catalytic activity and stability to the Ni or Cu counterparts. The synthesis parameters are also systematically tuned for optimizing the HzOR performance. The excellent HzOR performance of the Ni-Cu alloy film is attributed to its high intrinsic activity, large electrochemical specific surface area, and 3D porous architecture which offers a "superaerophobic" surface to effectively remove the gas product in a small volume. It is believed that the Ni-Cu alloy film electrode has potential application in direct hydrazine fuel cells as well as other catalytic fields. PMID- 26676883 TI - Kruppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells. AB - Osteosarcoma is the most common primary malignant bone tumor, and the frequent acquisition of chemoresistance is often an obstacle to achieving favorable outcomes during chemotherapy. Recently, Kruppel-like factor 4 (KLF4) has been shown to be associated with chemotherapy resistance in a few tumors; however, the involvement of KLF4 in chemotherapy resistance in osteosarcoma cells remains unknown. In this study, quantitative real-time PCR and western blot analysis revealed that KLF4 expression was significantly increased in response to cisplatin, methotrexate and doxorubicin treatment in osteosarcoma cells, and knockdown of KLF4 increased sensitivity to these anticancer drugs by decreasing cellular clonogenic ability and increasing apoptosis. Moreover, our data suggest that KLF4-regulated drug resistance might, at least partially, positively regulate high-mobility group box 1 (HMGB1), which was found to be a significant contributor to chemoresistance in osteosarcoma cells in our previous study. In summary, this study highlights the significance of KLF4/HMGB1 interaction in regulating chemotherapy resistance, and suggests that targeting KLF4/high mobility group box 1 may be a therapeutic strategy for osteosarcoma chemotherapy. PMID- 26676886 TI - Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma. AB - Rhabdomyosarcomas (RMS) are soft tissue tumours treated with a combination of surgery and chemotherapy. However, mortality rates remain high in case of recurrences and metastatic disease due to drug resistance and failure to undergo apoptosis. Therefore, innovative approaches targeting specific signalling pathways are urgently needed. We analysed the impact of different hedgehog (Hh) pathway inhibitors on growth and survival of six RMS cell lines using MTS assay, colony formation assay, 3D spheroid cultures, flow cytometry and western blotting. Especially the glioma-associated oncogene family (GLI) inhibitor arsenic trioxide (ATO) effectively reduced viability as well as clonal growth and induced cell death in RMS cell lines of embryonal, alveolar and sclerosing, spindle cell subtype, whereas normal skeletal muscle cells were hardly compromised by ATO. Combination of ATO with itraconazole potentiated the reduction of colony formation and spheroid size. These results show that ATO is a promising substance for treatment of relapsed and refractory RMS by directly targeting GLI transcription factors. The combination with itraconazole or other chemotherapeutic drugs has the opportunity to enforce the treatment efficiency of resistant and recurrent RMS. PMID- 26676888 TI - Trichiconlides A and B: two novel limonoids from the fruits of Trichilia connaroides. AB - Trichiconlides A (1) and B (2), two novel limonoids, were isolated from the fruits of Trichilia connaroides. Compound 1 is a novel limonoid with a highly rearranged A/B ring system and an intact D ring, which formed an unprecedented 5/6/5/6/5 carbon skeleton. Trichiconlide B (2) possesses a 10 oxatricyclo[3.3.1.(3,8)]decane core and formed a cage-like structure located between rings A and C. Their structures and absolute configurations were elucidated by spectroscopic methods, single crystal X-ray diffraction, the ECD exciton chirality method and TDDFT/ECD calculations. 1 showed a moderate inhibitory effect on nitric oxide (NO) production. PMID- 26676887 TI - Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis. AB - To establish the individualized treatment of patients with colorectal cancer, factors associated with chemotherapeutic effects should be identified. However, to the best of our knowledge, few studies are available on this topic, although it is known that the prognosis of patients and sensitivity to chemotherapy depend on the location of the tumor and that the tumor location is important for individualized treatment. In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Large-scale population analysis was performed to determine the association of gene expression with the clinicopathological features, in particular, the location of the colorectal cancer. From the results of our analysis of the mRNA expression of these 10 genes, we noted the strongest correlation between DPYD and TYMP, followed by TYMS and DHFR. The location of the colorectal cancer was classified into 4 regions (the right- and left-sided colon, rectosigmoid and rectum) and was compared with gene expression. A significant difference in all genes, apart from VEGF, was noted. Of the remaining 9 genes, the highest expression of TYMS and DPYD was observed in the right-sided colon; the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was approximately equivalent in the right-sided colon and rectum, and higher than that in other locations. The data generated from this study may prove to be useful for the development of individualized chemotherapeutic treatments for patients with colorectal cancer, and will mean that the tumor location is taken into account. PMID- 26676889 TI - Short- and long-term surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis: Relationships with neuropathology. AB - OBJECTIVE: Hippocampal sclerosis (HS) is the most frequent neuropathologic finding in patients undergoing surgery for intractable temporal lobe epilepsy (TLE). The International League Against Epilepsy (ILAE) has recently proposed a new classification of HS based on specific patterns of cell loss. The aim of this study was to investigate the relationships between HS types, their etiologic factors, and the short- and long-term postsurgical outcomes of patients undergoing surgery because of drug-resistant TLE with HS. METHODS: Two hundred thirteen patients with a neuropathologic diagnosis of HS and a minimum follow-up of 2 years were divided on the basis of their ILAE HS type and further classified into: (1) isolated HS, (2) HS associated with focal cortical dysplasia (FCD IIIa), or (3) HS associated with other lesions. Their clinical and neuropathologic data were correlated with their Engel class postsurgical outcomes. RESULTS: The main findings were the following: (1) HS type 1 was associated with a longer duration of epilepsy; (2) >80% of the patients had an Engel class I short- and long-term outcomes, regardless of HS type and associated pathology; (3) short- and long-term postsurgical outcomes were less satisfactory in the patients who were completely seizure-free (Engel class Ia), and patients with HS type 2 had better long-term seizure outcomes than those with type 1; (4) the concomitant presence of FCD contributed to a worse outcome, regardless of HS type; and (5) a shorter duration of epilepsy significantly correlated with an Engel class Ia outcome. SIGNIFICANCE: These data suggest that HS type and associated pathologies may predict the risk of recurrence, but other variables such as the duration of epilepsy need to be considered. A common neuropathologic classification system may help to identify preoperative predictive factors and improve the selection of patients who may benefit from epilepsy surgery. PMID- 26676890 TI - A stimuli-responsive nanoparticulate system using poly(ethylenimine)-graft polysorbate for controlled protein release. AB - Proteins have emerged as an important class of therapeutic agents due to their high specificity in their physiological actions. Over the years, diverse protein carriers have been developed; however, some concerns, such as the relatively low loading efficiency and release sustainability, have limited the efficiency of protein delivery. This study reports the use of hydrogel nanoparticles based on a novel copolymer, poly(ethylenimine)-graft-polysorbate (PEIP), as effective protein carriers. The copolymer is fabricated by grafting poly(ethylenimine) (PEI) with polysorbate 20 using carbonyldiimidazole chemistry. Its cytotoxicity is much lower than that of unmodified PEI in RGC5 and HEK293 cells. In comparison with nanoparticles formed by unmodified PEI, our nanoparticles are not only more efficient in cellular internalization, as indicated by the 5- to 6-fold reduction in the time they take to cause 90% of cells to exhibit intracellular fluorescence, but also give a protein loading efficiency as high as 70-90%. These, together with the salt-responsiveness of the nanoparticles in protein release and the retention of the activity of the loaded protein, suggest that PEIP and its hydrogel nanoparticles warrant further development as protein carriers for therapeutic applications. PMID- 26676891 TI - Application of recombinant peroxisome proliferator-activated receptor-gamma coactivator-1alpha mediates neovascularization in the retina. AB - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is able to induce the expression of vascular endothelial growth factor (VEGF), promoting the formation of new blood vessels in skeletal muscle. The aim of the current study was to determine whether PGC-1alpha is able to regulate angiogenesis in human retinal vascular endothelial cells (hRVECs) in vitro and in retinas in vivo. hRVECs treated with recombinant PGC-1alpha were incubated for 24 h and then placed into a normoxic (20% O2) or hypoxic (1% O2) environment for a further 16 h. Following this, VEGF mRNA and protein levels were significantly increased. Cellular proliferation was enhanced by treatment with recombinant PGC 1alpha in normoxic and hypoxic conditions. At 24 h following recombinant PGC 1alpha treatment, hRVECs were plated into Matrigel-coated plates and cultured under normoxic (20% O2) or hypoxic (1% O2) conditions for a further 24 h. Recombinant PGC-1alpha-treated cells were observed to form significantly greater numbers of tubes. In a C57BL/6J mouse model of ischemic retinopathy, mice received an intravitreal injection of recombinant PGC-1alpha, resulting in a significant increase in VEGF mRNA and protein levels in the retina. Retinal neovascular tufts and neovascular nuclei were investigated by angiographic and cross-sectional analysis and were observed to be significantly increased in the PGC-1alpha group compared with the control group. These results indicate that PGC 1alpha is able to induce angiogenesis in hRVECs and retinas, and suggests that PGC-1alpha is a potential anti-angiogenic target in retinal neovascularization. PMID- 26676892 TI - Enrichment of two isoflavone aglycones in black soymilk by Rhizopus oligosporus NTU 5 in a plastic composite support bioreactor. AB - BACKGROUND: A plastic composite support (PCS) bioreactor was implemented to evaluate the effects on isoflavone deglycosylation in black soymilk fermented by Rhizopus oligosporus NTU 5. RESULTS: Evaluation for the optimal PCS for mycelia immobilisation was conducted, which led to the significant results that the most mycelium weight (0.237 g per PCS, P < 0.05) is held by an S-type PCS; therefore, it was selected for black soymilk fermentation. It was found that the PCS fermentation system without pH control exhibits better efficiency of isoflavone bioconversion (daidzin to daidzein, and genistin to genistein) than the one with pH control at pH 6.5. As for the long-run fermentation, those without pH control indeed accelerate the isoflavone bioconversion by continuously releasing beta glucosidase into soymilk. Deglycosylation can be completed in 8 to 24 h and sustained for at least 34 days as 26 batches. The non-pH-control fermentation system also exhibits the highest total phenolic content (ranged from 0.147 to 0.340 mg GAE mL(-1) sample) when compared to the pH-controlled and suspended ones. Meanwhile, the black soymilk from the 22nd batch with 8 h fermentation demonstrated the highest DPPH radical scavenging effect (54.7%). CONCLUSION: A repeated-batch PCS fermentation system was established to accelerate the deglycosylation rate of isoflavone in black soymilk. (c) 2015 Society of Chemical Industry. PMID- 26676893 TI - Timothy Moynihan, MD, on 'Death Cafes' and the Importance of Discussing End-of Life Issues With Your Patients. PMID- 26676895 TI - New Insights Into the Immunomodulatory Effects of Exercise and Potential Impact on Tumorigenesis. PMID- 26676896 TI - Large Bladder Mass and Renal Failure in a 14-Year-Old Boy. PMID- 26676894 TI - Exercise in Regulation of Inflammation-Immune Axis Function in Cancer Initiation and Progression. AB - Pharmacologic manipulation of the immune system is emerging as a viable and robust treatment for some cancer patients. Exercise-induced modulation of the immune system may be another adjunctive strategy for inhibiting tumor initiation and progression. In healthy individuals, exercise has been shown to modulate a number of cell subsets involved in innate and adaptive immunity. Here, we provide an overview of the current state of knowledge pertaining to exercise modulation of the inflammation-immune axis in cancer. The current evidence suggests that exercise may be a promising adjunctive strategy that can favorably alter numerous components of the immune system, which, in turn, may modulate tumorigenesis. However, many important knowledge gaps are evident. To this end, we propose a framework to guide future research efforts investigating the immune effects of exercise in cancer. PMID- 26676897 TI - Screening and Prevention of Hepatitis B Virus Reactivation During Chemotherapy. PMID- 26676898 TI - Clinical Issues in the Surgical Management of Screen-Identified Lung Cancers. AB - The National Lung Screening Trial reported a 20% reduction in lung cancer specific mortality in patients screened with low-dose computed tomography (CT) compared with those screened by plain chest radiography. This led to the endorsement of CT screening for lung cancer by the US Preventive Services Task Force and the subsequent approval of screening as a preventive health service reimbursable by the Centers for Medicare and Medicaid Services. This review outlines the diagnostic and therapeutic challenges associated with the increased number of screen-identified indeterminate lung nodules, highlighting currently recommended follow-up and management algorithms, as well as the various methods of nodule localization, tissue diagnosis, and definitive local therapeutic modalities. PMID- 26676899 TI - CT Screening for Lung Cancer: How to Fulfill the Promise. PMID- 26676900 TI - Upfront Chemotherapy for Metastatic Prostate Cancer. AB - Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID- 26676901 TI - Chemotherapy in Prostate Cancer Beyond Metastatic CRPC. PMID- 26676902 TI - Mutation-Derived Tumor Antigens: Novel Targets in Cancer Immunotherapy. PMID- 26676903 TI - Implementing Survivorship Care Plans Within an Electronic Health Record. PMID- 26676904 TI - Association between subjective memory complaints and depressive symptoms after adjustment for genetic and family environmental factors in a Japanese twin study. AB - OBJECTIVES: The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors. METHODS: We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors. RESULTS: We included 556 twins aged >= 20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95% CI 0.08-0.38); females, 0.35 (95% CI 0.23-0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95% CI 0.08-0.56); females, 0.24 (95% CI 0.13-0.42)]. CONCLUSIONS: This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors. PMID- 26676905 TI - Hepatocyte growth factor (HGF) and hemodialysis: physiopathology and clinical implications. AB - Hepatocyte growth factor (HGF) is a pleiotropic cytokine which exerts a variety of effects on several cells, being involved in the regulation of many biological processes, such as inflammation, tissue repair, morphogenesis, angiogenesis, tumour propagation, immunomodulation of viral infections and cardio-metabolic activities. Patients undergoing regular hemodialysis (HD) present elevated levels of HGF, mainly due to the leukocyte activation associated with HD treatment. High HGF levels might account for specific clinical features of HD patients, i.e. mild liver damage in course of HCV-infection and high cardiovascular risk profile. Moreover, in patients with acute kidney injury, the induction of HGF may represent a crucial step to promote renal recovery, which can have important prognostic consequences in the short and long-term. In this review we discuss the mechanisms underlying HGF production in HD patients, the role of HGF in this particular patient population and the potential clinical implications derived from the study of HGF in HD patients. PMID- 26676907 TI - Organic Solvent Effects in Biomass Conversion Reactions. AB - Transforming lignocellulosic biomass into fuels and chemicals has been intensely studied in recent years. A large amount of work has been dedicated to finding suitable solvent systems, which can improve the transformation of biomass into value-added chemicals. These efforts have been undertaken based on numerous research results that have shown that organic solvents can improve both conversion and selectivity of biomass to platform molecules. We present an overview of these organic solvent effects, which are harnessed in biomass conversion processes, including conversion of biomass to sugars, conversion of sugars to furanic compounds, and production of lignin monomers. A special emphasis is placed on comparing the solvent effects on conversion and product selectivity in water with those in organic solvents while discussing the origins of the differences that arise. We have categorized results as benefiting from two major types of effects: solvent effects on solubility of biomass components including cellulose and lignin and solvent effects on chemical thermodynamics including those affecting reactants, intermediates, products, and/or catalysts. Finally, the challenges of using organic solvents in industrial processes are discussed from the perspective of solvent cost, solvent stability, and solvent safety. We suggest that a holistic view of solvent effects, the mechanistic elucidation of these effects, and the careful consideration of the challenges associated with solvent use could assist researchers in choosing and designing improved solvent systems for targeted biomass conversion processes. PMID- 26676906 TI - Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study. AB - BACKGROUND: Trimethylamine-N-oxide (TMAO) is a metabolite of phosphatidylcholine generated by gut microbiota and liver enzymes, and has recently been recognized as contributing to atherosclerosis. Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease (sudden death, myocardial infarction, or stroke) in patients undergoing elective coronary angiography. We aimed to clarify whether TMAO levels are associated with the number of infarcted coronary arteries as a measure of the severity of atherosclerosis, with adjustment using a priori-defined covariates such as kidney function. METHODS: By conducting a cross sectional study of 227 patients who underwent cardiovascular surgery for coronary artery disease, valvular heart disease, or aortic disease, the association between serum TMAO levels as measured by HPLC-APCI-MS/MS and the number of infarcted coronary arteries was evaluated using ordered logistic regression models with adjustment of 10 covariates, including chronic kidney disease (CKD) stage. Unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined. RESULTS: Significantly higher TMAO levels were observed in advanced-stage CKD (p <= 0.001). In fully adjusted models with the 10 covariates, a significantly increased number of infarcted coronary arteries was identified in the highest quartile and quintile of TMAO compared to the lowest quartile (OR 11.9; 95 % CI 3.88-36.7, p <= 0.001) and quintile (OR 14.1; 95 % CI 3.88-51.2; p <= 0.001), respectively, independent of dyslipidemia. CONCLUSIONS: Higher serum TMAO levels may be associated with advanced CKD stages and with an increased number of infarcted coronary arteries in patients who undergo cardiovascular surgery. PMID- 26676908 TI - Efficacy and safety of saxagliptin monotherapy or added to metformin in Chinese patients with type 2 diabetes mellitus: results from the 24-week, post-marketing SUNSHINE study. AB - BACKGROUND: The aim of the present study was to explore the efficacy and safety of saxagliptin in a large Chinese population with type 2 diabetes mellitus (T2DM). METHODS: In all, 1423 T2DM patients from 92 research centers, either drug naive or uncontrolled by metformin, were enrolled in this single-arm cohort study; patients were treated with saxagliptin 5 mg once daily for 24 weeks. The primary efficacy endpoint was the change from baseline in HbA1c at 24 weeks in the per-protocol analysis set. Secondary endpoints included the proportion of patients achieving HbA1c <7% and changes from baseline in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (PPG) concentrations at 24 weeks. Safety endpoints included adverse events (AEs) and the incidence of hypoglycemia. RESULTS: Among 1210 patients in the per-protocol analysis set, mean HbA1c, FPG and 2-h PPG decreased by 1.61 +/- 0.04%, 0.55 +/- 0.07 mmol/L, and 2.83 +/- 0.27 mmol/L, respectively, at week 24. The proportion of patients achieving HbA1c <7% was 44.1%. No new (previously unreported) AEs occurred. The incidence of serious AEs and hypoglycemia was low (1.8% and 1.2%, respectively). There were no significant differences in efficacy endpoints in subgroup analyses by age, creatinine clearance, body mass index, or treatment background. In elderly patients (>=65 years) and those with mild renal impairment (50 < CCr <= 80 mL/min), the incidence of AEs was similar to that of the entire study population. CONCLUSIONS: Saxagliptin significantly improved glycemic control and was well tolerated in Chinese T2DM patients, including the elderly and patients with mild renal impairment. PMID- 26676909 TI - Determination of a suitable voriconazole pharmacokinetic model for personalised dosing. AB - Model based personalised dosing (MBPD) is a sophisticated form of individualised therapy, where a population pharmacokinetic (PK) or pharmacodynamic model is utilised to estimate the dose required to reach a target exposure or effect. The choice of which model to implement in MBPD is a subjective decision. By choosing one model, information from the remaining models is ignored, as well as the rest of the literature base. This manuscript describes a methodology to develop a 'hybrid' model for voriconazole that incorporated information from prior models in a biologically plausible manner. Voriconazole is a triazole antifungal with difficult to predict PK, although it does have a defined exposure-response relationship. Nine population PK models of voriconazole were identified from the literature. The models differed significantly in structural components. The hybrid model contained a two-compartment disposition model with mixed linear and nonlinear time-dependent clearance. The parameters for the hybrid model were determined using simulation techniques. Validation of the hybrid model was assessed via visual predictive checks, which indicated the majority of the variability in the literature models was captured by the hybrid model. The predictive performance was assessed using four different sampling strategies of limited concentrations from ten richly PK sampled subjects to predict future concentrations. Overall, the hybrid model predicted future concentrations with good precision. Further prospective and retrospective validation of the hybrid model is required before it could be used in clinical practice. PMID- 26676910 TI - Concise Total Synthesis of Dehaloperophoramidine. AB - Perophoramidine, dehaloperophoramidine, and communesin F are structurally related alkaloids having intriguing polycyclic structures. A strategy for the synthesis of dehaloperophoramidine has been developed. In this synthesis all skeletal atoms and all functional groups required to reach the target molecule are incorporated early in the sequence. This approach led to the discovery of two novel substrate specific domino processes, one encompassing four steps and the other comprising five steps, thus resulting in an eight-step synthesis of dehaloperophoramidine. PMID- 26676911 TI - Changes in the mean echogenicity and area of the puborectalis muscle during pregnancy and postpartum. AB - INTRODUCTION AND HYPOTHESIS: Three-dimensional (3D) and four-dimensional (4D) volume transperineal ultrasound imaging is increasingly used to assess changes in the dimensions of the pelvic floor during pregnancy and after delivery. Little is known with regard to the area of the puborectalis muscle and its structural changes. Echogenicity measurement, a parameter that provides information on the structure of muscles, is increasingly used in orthopaedics and neuromuscular disease evaluation. This study is aimed at assessing the changes in the mean echogenicity of the puborectalis muscle (MEP) and the puborectalis muscle area (PMA) during first pregnancy and after childbirth. METHODS: The MEP and PMA of 254 women during first pregnancy were measured at 12 and 36 weeks' gestation and 6 months postpartum. To determine the effect of child-birth on MEP and PMA, the results at 6 months postpartum were separately analysed for vaginal deliveries, operative vaginal deliveries (ventouse) and caesarean section deliveries. Mean differences in MEP and PMA were analysed using ANOVA statistics. RESULTS: The MEP at 6 months postpartum was, independent of manoeuvre, significantly (p < 0.001) lower than MEP values during pregnancy. After caesarean delivery, the PMA was significantly smaller at maximum pelvic floor contraction than PMA after vaginal delivery (p = 0.003) or operative vaginal delivery (p = 0.002). CONCLUSION: Our study indicates that structural changes in the puborectalis muscle during and after pregnancy, as measured by MEP, occur and can be analysed. In addition, the mode of delivery affects the area of the puborectalis during contraction after delivery. For true volume analysis, as part of an assessment of contractility of the puborectalis muscle we will need 3D volume analysis. PMID- 26676912 TI - Risk factors for recurrent obstetric anal sphincter injury (rOASI): a systematic review and meta-analysis. AB - OBJECTIVES: The objective of this study was to estimate the risk of recurrent obstetric anal sphincter injury (rOASI) in women who have suffered anal sphincter injury in their previous pregnancy and analyse risk factors for recurrence through a systematic review and meta-analysis. DATA SOURCES: A review was performed according to Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Searches were made in Ovid MEDLINE (1996 to May 2015), PubMed, EMBASE and Google Scholar, including bibliographies and conference proceedings. METHODS OF STUDY SELECTION: Observational studies (cohort/case control) evaluating rOASI and risk factors were selected by two reviewers who also analysed methodological quality of those studies. Pooled odds ratios (OR) for rOASI and individual risk factors were calculated using RevMan 5.3. TABULATION, INTEGRATION AND RESULTS: From the eight studies assessed, overall risk of rOASI was 6.3 % compared with a 5.7 % risk of OASI in the first pregnancy. The risk in parous women with no previous OASI was 1.5 %. Factors that increased the risk in a future pregnancy were instrumental delivery with forceps [OR 3.12, 95 % confidence interval (CI) 2.42-4.01) or ventouse (OR 2.44, 95 % CI 1.83-3.25), previous fourth-degree tear (OR 1.7, 95 % CI 1.24-2.36) and birth weight >=4 kg (OR 2.29, 95 % CI 2.06-2.54). Maternal age >=35 years marginally increased the risk (OR 1.16, 95 % CI 1-1.35). CONCLUSION: The overall rate of rOASI and associated risk factors for recurrence are similar to the rate and risk factors of primary OASI. Antenatal decisions could be based on assessment of foetal weight and intrapartum decisions based upon the requirement for an instrumental delivery. PMID- 26676913 TI - Republished: Patients teaching patient safety: the challenge of turning negative patient experiences into positive learning opportunities. PMID- 26676914 TI - Republished: Marfan syndrome, inherited aortopathies and exercise: What is the right answer? AB - Exercise recommendations for those who have Marfan syndrome or other genetic predisposition for thoracic aortic disease remain controversial and at times ambiguous. There are no outcomes studies to help guide recommendations. In this review, we examine the guidelines regarding exercise and inherited aortic conditions, the theoretical reasoning and circumstantial evidence that support the guidelines, as well as the knowledge gaps that continue to exist. PMID- 26676915 TI - The case of Emma Eckstein. PMID- 26676916 TI - The Generalizability of Overreporting Across Self-Report Measures: An Investigation With the Minnesota Multiphasic Personality Inventory-2-Restructured Form and the Personality Assessment Inventory in a Civil Disability Sample. AB - Elevated overreporting Validity Scale scores on the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) are associated with higher scores on collateral measures; however, measures used in prior research lacked validity scales. We sought to extend these findings by examining associations between elevated MMPI-2-RF overreporting scale scores and Personality Assessment Inventory (PAI) scale scores among 654 non-head injury civil disability claimants. Individuals were classified as overreporting psychopathology (OR-P), overreporting somatic/cognitive complaints (OR-SC), inconclusive reporting psychopathology (IR-P), inconclusive reporting somatic/cognitive complaints (IR SC), or valid reporting (VR). Both overreporting groups had significantly and meaningfully higher scores than the VR group on the MMPI-2-RF and PAI scales. Both IR groups had significantly and meaningfully higher scores than the VR group, as well as lower scores than their overreporting counterparts. Our findings demonstrate the utility of inventories with validity scales in assessment batteries that include instruments without measures of protocol validity. PMID- 26676917 TI - The Personality Inventory for DSM-5 Brief Form: Evidence for Reliability and Construct Validity in a Sample of Community-Dwelling Italian Adolescents. AB - To assess the reliability and construct validity of the Personality Inventory for DSM-5 Brief Form (PID-5-BF) among adolescents, 877 Italian high school students were administered the PID-5-BF. Participants were administered also the Measure of Disordered Personality Functioning (MDPF) as a criterion measure. In the full sample, Cronbach's alpha values for the PID-5-BF scales ranged from .59 (Detachment) to .77 (Psychoticism); in addition, all PID-5-BF scales showed mean interitem correlation values in the .22 to .40 range. Cronbach's alpha values for the PID-5-BF total score was .83 (mean interitem r = .16). Although 2-month test retest reliability could be assessed only in a small ( n = 42) subsample of participants, all PID-5-BF scale scores showed adequate temporal stability, as indexed by intraclass r values ranging from .78 (Negative Affectivity) to .97 (Detachment), all ps <.001. Exploratory structural equation modeling analyses provided at least moderate support for the a priori model of PID-5-BF items. Multiple regression analyses showed that PID-5-BF scales predicted a nonnegligible amount of variance in MDPF Non-Cooperativeness, adjusted R2 = .17, p < .001, and Non-Coping scales, adjusted R2 = .32, p < .001. Similarly, the PID 5-BF total score was a significant predictor of both MDPF Non-Coping, and Non Cooperativeness scales. PMID- 26676919 TI - Frequency of cutis laxa-like clinical features and elastolysis in scleromyxedema: a retrospective clinicopathologic study of 19 patients with scleromyxedema. AB - BACKGROUND: Cutis laxa-like features were observed in a subset of patients with scleromyxedema. Given this observation, clinical and histopathologic features of scleromyxedema were reviewed in correlation with elastic tissue staining. METHODS: We retrospectively reviewed clinical records and histopathologic features from patients with scleromyxedema seen at our institution from 1992 through 2013. We also evaluated available skin biopsies with an elastin stain and assessed whether dermal elastin fibers were diminished in density or were fragmented (or both). RESULTS: Nineteen patients with scleromyxedema and 34 skin biopsies were identified. Alcian blue (mucin) stain was used to grade mucin deposition as weakly positive (24%), positive (44%) and markedly positive (32%). Eight patients (42%) had clinical findings of cutis laxa, which were often observed in conjunction with areas of papular eruption or induration. Elastic tissue fibers were normal in 9 of 34 skin specimens (26%), 18 of 34 specimens (53%) had diminished elastic fiber density and 7 of 34 (21%) had markedly decreased density. The elastic tissue was fragmented in 25 specimens (74%). CONCLUSIONS: A cutis laxa-like clinical presentation and decreased elastic tissue density on skin biopsy were consistent findings. Dermatologists and dermatopathologists should be aware of these previously unreported clinical and histopathologic findings. PMID- 26676918 TI - The effects of self-focus on attentional biases in social anxiety:An ERP study. AB - Cognitive theories of social anxiety disorder suggest that biased attention plays a key role in maintaining symptoms. These biases include self-focus and attention to socially threatening stimuli in the environment. The goal of this study was to utilize ERPs that are elicited by a change detection task to examine biases in selective attention (i.e., N2pc) and working memory maintenance (i.e., contralateral delay activity; CDA). Additionally, the effect of self-focus was examined using false heart rate feedback. In support of the manipulation, self focus cues resulted in greater self-reported self-consciousness and task interference, enhanced anterior P2 amplitude and reduced SPN amplitude. Moreover, P2 amplitude for self-focus cues was correlated with reduced task performance for socially anxious subjects only. The difference in P2 amplitude between self-focus and standard cues was correlated with social anxiety independent of depression. As hypothesized, socially anxious participants (n = 20) showed early selection and maintenance of disgust faces relative to neutral faces as indicated by the N2pc and CDA components. Nonanxious controls (n = 22) did not show these biases. During self-focus cues, controls showed marginal evidence of biased selection for disgust faces, whereas socially anxious subjects showed no bias in this condition. Controls showed an ipsilateral delay activity after being cued to attend to one hemifield. Overall, this study supports early and persistent attentional bias for social threat in socially anxious individuals. Furthermore, self-focus may disrupt these biases. These findings and supplementary data are discussed in light of cognitive models of social anxiety disorder, recent empirical findings, and treatment. PMID- 26676920 TI - Multi-model approach to characterize human handwriting motion. AB - This paper deals with characterization and modelling of human handwriting motion from two forearm muscle activity signals, called electromyography signals (EMG). In this work, an experimental approach was used to record the coordinates of a pen tip moving on the (x, y) plane and EMG signals during the handwriting act. The main purpose is to design a new mathematical model which characterizes this biological process. Based on a multi-model approach, this system was originally developed to generate letters and geometric forms written by different writers. A Recursive Least Squares algorithm is used to estimate the parameters of each sub model of the multi-model basis. Simulations show good agreement between predicted results and the recorded data. PMID- 26676921 TI - Barriers and facilitators towards fertility preservation care for cancer patients: a meta-synthesis. AB - Infertility is a potential late-effect of cancer treatment, which negatively impact on young cancer survivors' quality of life. This paper aims to synthesise factors that influence patients', carers' and healthcare professionals' decision to engage in fertility preservation programmes at the time of cancer diagnosis. Four databases and grey literature were systematically searched to identify qualitative and mixed-method studies published between 2000 and 2015. Thematic framework and synthesis were used to analyse and synthesise the data. Thirty seven papers were selected and represented. Factors that affect engagement of patients, carers and healthcare providers in fertility preservation care can be grouped as intrinsic and extrinsic. Intrinsic factors include patients' attitudes, health beliefs and health literacy; clinicians' approaches and skills; as well as doctor-patient relationships. Extrinsic factors include fertility preservation care resources and institutional characteristics. We conclude that existing qualitative literature highlights the complex convergences of intrinsic and extrinsic factors that impede successful engagement in fertility preservation care. Addressing these factors could help cancer survivors achieve better health outcomes and improve their wellbeing. Potential solutions include attitudinal changes and organisational skill reforms across the health community that will help ensure a person's goals are always at the centre of their cancer care. PMID- 26676922 TI - Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. AB - BACKGROUND: Parkinson's disease (PD) and multiple system atrophy (MSA) are two neurodegenerative alpha-synucleinopathies characterized by severe impairment of the nigro-striatal pathway. Based on T1-, T2*-, and diffusion-weighted magnetic resonance imaging (MRI), macro-structural and micro-structural abnormalities in these diseases can be detected. OBJECTIVE: This study was undertaken to compare the nigro-striatal changes that occur in patients with PD with those in patients with both variants of MSA (the parkinsonian variant, MSA-P, and the cerebellar variant, MSA-C), and to explore correlations between different MRI parameters and clinical data. METHODS: We simultaneously measured volume, T2* relaxation rates, and mean diffusivity in nigro-striatal structures (substantia nigra, caudate nucleus, and putamen) of 26 patients with PD and 29 patients with MSA (16 with MSA-P and 13 with MSA-C). RESULTS: Significant changes in the putamina in patients with MSA were observed compared with patients with PD. Patients with MSA P had higher mean diffusivity values in their putamina than did patients with PD or MSA-C. The putamina of both subgroups of MSA had higher T2* relaxation rates values than PD. Remarkably, discriminant analysis showed that using two measurements of microstructural damage (T2* relaxation rates and mean diffusivity in the putamen) allowed 96% accuracy to distinguish patients with PD from those with MSA-P. Correlation analyses between MRI findings and clinical variables revealed that patients with PD showed significant correlations only at the nigra. In patients with MSA, clinical variables correlated with MRI findings in both the nigra and striatum. CONCLUSIONS: Multimodal MRI reveals different pattern of nigro-striatal involvement in patients with PD and patients with MSA. PMID- 26676923 TI - Bullae and Erosions on Sun-Exposed Skin. PMID- 26676924 TI - Dynamic Behavior in Enzyme-Polymer Surfactant Hydrogel Films. AB - Dynamic protein-polymer surfactant films are highly hydrophilic and show a soft solid to hydrogel transition upon hydration to produce a swollen hydrogel. An unusual reversible autospreading/self-folding response is observed when the water saturated films are transferred from water into air. PMID- 26676925 TI - Association of prenatal exposure to acetaminophen and coffee with childhood asthma. AB - PURPOSE: Some studies have suggested that maternal acetaminophen use during pregnancy is associated with asthma in the offspring, and coffee consumption may modify the toxicity of acetaminophen. We aim to examine whether pregnancy maternal acetaminophen use increases the risk for offspring asthma, and whether such a potential association could be modified by maternal coffee consumption. METHODS: We included 63,652 live-born singletons enrolled in the Danish National Birth Cohort. Maternal acetaminophen use and coffee consumption during pregnancy were assessed prospectively via the enrolment questionnaire and three computer assisted telephone interviews. Asthma cases were identified by using the Danish National Patient Register and the Danish National Prescription Registry. We estimated the hazard ratios (HRs) for asthma according to prenatal acetaminophen and coffee exposure using Cox proportional hazards regression model. RESULTS: After adjusting for potential confounders, acetaminophen use during pregnancy was associated with an increased risk of offspring asthma (HR = 1.16, 95% confidence interval (CI): 1.11-1.22). Coffee drinking during pregnancy was associated with a slightly decreased risk (HR = 0.94, 95%CI: 0.90-0.99). But there was no strong evidence of effect measure modification of acetaminophen use on offspring asthma by coffee consumption. CONCLUSIONS: Acetaminophen use during pregnancy was associated with a modest increased risk for offspring asthma, which was not modified by coffee consumption. PMID- 26676926 TI - Analysis of novel microRNA targets in drug-sensitive and -insensitive small cell lung cancer cell lines. AB - Advances in chemotherapy have failed to improve the long-term survival rate of small cell lung cancer (SCLC) patients due to multidrug resistance (MDR). The mechanisms of MDR are complex involving multiple genes and a variety of mechanisms. MicroRNAs (miRNAs) are non-coding RNAs theoretically involved in gene regulation. The aim of the present study was to explore the role of miRNAs in SCLC occurrence and multidrug resistance. Expression levels of known miRNAs in SCLC cell line H446 and its multidrug-resistant cell line H446/CDDP were analyzed using the next generation high through-put Illumina Solexa sequencing technology, and expression of a group of specific miRNAs was validated by quantitative polymerase chain reaction (qPCR). Furthermore, novel miRNAs and their putative target genes in the two SCLC cell lines were predicted with the help of software developed by Beijing Genomics Institute and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed a set of known miRNAs with altered expression in the H446 and H446/CDDP cells which may be associated with multidrug resistance of SCLC. Biological information analysis of the novel miRNAs and their putative target genes further elucidated the role of miRNAs in MDR. In addition, the pathway prediction by KEGG analysis may provide clues for further research on MDR of SCLC. PMID- 26676927 TI - Supportive management strategies for disseminated intravascular coagulation. An international consensus. AB - The cornerstone of the management of disseminated intravascular coagulation (DIC) is the treatment of the underlying condition triggering the coagulopathy. However, a number of uncertainties remain over the optimal supportive treatment. The aim of this study was to provide evidence and expert-based recommendations on the optimal supportive haemostatic and antithrombotic treatment strategies for patients with DIC. A working group defined five relevant clinical scenarios. Published studies were systematically searched in the MEDLINE and EMBASE databases (up to May 2014). Seven internationally recognised experts were asked to independently provide clinical advice. A two-phase blinded data collection technique was used to reach consensus. Only three randomised controlled trials (RCTs) on the supportive management of DIC were identified. The RCTs (overall less than 100 patients) investigated the use of fresh frozen plasma and platelet transfusion and found no differences in survival between the intervention and control groups. The experts' approach was heterogeneous, although there was consensus that supportive management should vary according to the underlying cause, clinical manifestations and severity of blood test abnormalities. Platelet transfusion should be given to maintain platelet count > 50*109/l in case of bleeding while a lower threshold of 20 to 30*109/l may be used in DIC without bleeding. Thromboprophylaxis with low-molecular-weight heparin is advised until bleeding ensues or platelet count drops below 30*109/l. In conclusion, in the absence of solid evidence from RCTs, an individualised supportive management of DIC is advisable based on the type of underlying disease, presence of bleeding or thrombotic complications and laboratory tests results. PMID- 26676928 TI - A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leukemia cells. AB - Oridonin, obtained from the traditional Chinese herbal medicine rabdosia rubescens, exerts potent antitumor activities in cancer cells. Valproic acid (VPA), as a potent histone deacetylase inhibitor (HDACI), also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between oridonin and VPA for anti-leukemic effect. Therefore, in the present study, we undertook experiments to determine whether lower concentration of oridonin in conjunction with lower concentration of VPA would produce even more encouraging synergistic effect than each of them alone, and to clarify its molecular mechanism. The results demonstrated that the lower concentration of oridonin in combination with lower concentration of VPA synergistically inhibited the proliferation of HL-60 cells, and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway, which is involved in the downregulation of Bcl-2/Bax ratio, release of cytochrome c to cytosol and caspase-9 activation, as well as through the extrinsic apoptosis pathway mediated by Fas/FasL and caspase-8 activation. In addition, MAPK signaling pathway was also involved in apoptosis induced by oridonin plus VPA. Furthermore, the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis. Taken together, the novel combination of oridonin plus VPA exerted synergistic anti proliferative and apoptosis-inducing effects on human myeloid leukemia cells, and may serve as a potential promising anti-leukemia strategy. PMID- 26676929 TI - En Bloc Hilar Dissection of the Right Hepatic Artery in Continuity with the Bile Duct: a Technique to Reduce Biliary Complications After Adult Living-Donor Liver Transplantation. AB - OBJECTIVE: Techniques that preserve the right hepatic artery and the common bile duct in continuity during the dissection may be associated with lower rates of biliary complications in living-donor liver transplants. This study sought to determine whether en bloc hilar dissections were associated with fewer biliary complications in living-donor liver transplants. METHODS: This was a retrospective review of 41 adult LDLTs performed in a single, liver transplant center between February 2007 and September 2014. The primary outcome of interest was the occurrence of at least one of the following biliary complications: anastomotic leak, stricture, or biloma. The primary predictor of interest was the hilar dissection technique: conventional hilar dissection vs. en bloc hilar dissection. RESULTS: A total of 41 LDLTs were identified, 24 had a conventional, and 17 an en bloc hilar biliary dissection. The occurrence of any biliary complication was significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (66.7 vs. 35.3%, respectively, p = 0.047). In particularly, anastomotic strictures were significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (54.2 vs. 23.5%., respectively, p = 0.049). CONCLUSION: En bloc hilar dissection technique may decrease biliary complication rates in living donor liver transplants. PMID- 26676930 TI - Primary Gastrointestinal Non-Hodgkin's Lymphoma of the Small and Large Intestines: a Systematic Review. AB - BACKGROUND: Primary gastrointestinal non-Hodgkin's lymphoma (PGINHL) of small and large intestines is a group of heterogeneous, rare malignancies. Optimal treatment practices remain undefined. METHODS: A systematic review (2003-2015) was performed to assess tumor characteristics, treatment practices, and treatment outcomes of PGINHL of small and large intestines. RESULTS: Twenty-eight studies (1658 patients) were included; five focused on follicular lymphoma subtype. Of the non-follicular patients, 59.3% presented with abdominal pain, 37.2% were located in ileocecum, and 53.6% were diffuse large B cell lymphoma subtype. The majority of patients (60.7%) were treated with a combination of surgery and chemotherapy. Forty-three percent of studies concluded an overall survival benefit with surgery; none reported increased postoperative morbidity or mortality. Survival outcomes were not typically stratified by emergent versus elective surgery. Multivariate analysis within individual studies associated B cell lymphoma and ileocecum location with higher survival, while advanced stage and B symptoms were associated with poorer survival. Patients with asymptomatic follicular lymphoma had no progression with a watchful waiting approach. CONCLUSIONS: The majority of patients with non-follicular small and large intestinal PGINHLs are treated with both chemotherapy and surgery. Although surgery appears to be an important part of the treatment algorithm, definitive statements regarding its survival benefit remain limited due to lack of patient stratification based on timing and indication for surgery. PMID- 26676931 TI - Impact of Transfusion Threshold on Infectious Complications After Ileal Pouch Anal Anastomosis. AB - BACKGROUND: This study was conducted to investigate the impact of different hemoglobin level-based transfusion practices on infectious complications after surgery for ulcerative colitis. METHODS: Patients who underwent ileal pouch-anal anastomosis for ulcerative colitis between January 2008 and December 2013 were identified and divided into four groups: group 1 with hemoglobin >= 10 and group 2 with hemoglobin >= 7 and <10 g/dL who did not receive transfusion and group 3 with hemoglobin >= 7 and <10 and group 4 with hemoglobin < 7 g/dL who received transfusion. Clinical characteristics and septic complications within postoperative 30 days were compared. RESULTS: There were 237, 341, 40, and 20 patients in groups 1, 2, 3, and 4, respectively. All the groups were comparable regarding perioperative characteristics except for age, gender, preoperative albumin and hemoglobin levels, and operative blood loss. The rates of overall septic complications were 18.6, 26.7, 47.5, and 40 % in the groups 1, 2, 3 and 4, respectively. In multivariate analysis, compared to group 2, group 3 was associated with an increased likelihood of developing organ/space (odds ratio (OR) = 4.34, p = 0.004) and overall surgical site infections (SSIs) (OR = 2.81, p = 0.01). CONCLUSION: Blood transfusion decided based on a perioperative hemoglobin (Hgb) level above 7 mg/dL is associated with higher overall and organ/space SSIs. PMID- 26676932 TI - Experimental models of Alzheimer's disease for deciphering the pathogenesis and therapeutic screening (Review). AB - Despite decades of laboratory and clinical research, Alzheimer's disease (AD) is still the leading cause of dementia in adults and there are no curative therapies currently available for this disease. This may be due to the pathological features of AD, which include extensive extracellular amyloid plaques and intracellular neurofibrillary tangles, as well as subsequent neuronal and synaptic loss, which begin to appear several years prior to memory loss and the damge is already irreversible and extensive at the time of clinical diagnosis. The poor therapeutic effects of current treatments necessitate the introduction of experimental models able to replicate AD pathology, particularly in the pre symptomatic stage, and then to explore preventive and therapeutic strategies. In response to this necessity, various experimental models reproducing human AD pathology have been developed, which are also useful tools for therapeutic screening. Although none of these models fully reproduce the key features of human AD, the experimental models do provide important insight into the pathological changes which occur in AD. This review summarizes the commonly used experimental models of AD and also discusses how the models may be used to decipher the pathogenesis underlying AD and to screen novel therapies for this disease. PMID- 26676935 TI - Editorial: Funding Couple and Family Research. PMID- 26676934 TI - Tetramethylpyrazine protects CoCl2-induced apoptosis in human umbilical vein endothelial cells by regulating the PHD2/HIF/1alpha-VEGF pathway. AB - Tetramethylpyrazine (TMP), one of the active ingredients isolated from a Chinese herbal prescription, possesses protective effects against apoptosis in endothelial cells. However, the underlying mechanism of its protective effects in endothelial cells remains to be elucidated. Using human umbilical vein endothelial cells (HUVECs), the present study assessed the protective effects of TMP on CoCl2-induced apoptosis. Following pre-incubation with CoCl2 (150 uM/ml) for 4 h, the HUVECs were treated with TMP at different concentrations (50, 100 and 200 uM/ml) for 8 h. TMP upregulated the expression of prolyl hydroxylase (PHD)2, reduced the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), and reduced the expression of HIF-1alpha only at the protein level, not at the mRNA level in HUVECs, in a concentration-dependent manner. Furthermore, silencing of the PHD2 gene with small interfering (si)RNAs abolished the reduction in the expression of hypoxia-inducible factor (HIF) 1alpha and VEGF by TMP. In addition, TMP protected CoCl2-induced HUVEC injury via an apoptosis pathway, as characterized by the increased ratio of cell viability and the reduced percentage of apoptotic and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive HUVECs, activation of caspase-3, -8 and -9, B cell lymphoma (Bcl)-2/Bcl-2-activated X protein expression, as well as the release of cytochrome c. The protective properties of TMP were partially attributed to the mRNA and protein expression levels of PHD, since silencing of the PHD2 gene with siRNAs abolished these effects. The present study demonstrated that the antiapoptotic effect of TMP in CoCl2-induced HUVECs was, at least in part, via the regulation of the PHD2/HIF-1alpha signaling pathway. PMID- 26676936 TI - Highly efficient synthesis of flavonol 5-O-glycosides with glycosyl ortho alkynylbenzoates as donors. AB - With glycosyl ortho-alkynylbenzoates as donors, the highly efficient glycosylation of flavonoid 5-OH which are notorious for their low reactivity due to their involvement in the formation of strong intramolecular H-bonds was achieved under the catalysis of a Au(i) complex. Thus, a series of flavonoid 5-O glycosides, including a kaempferol 5-O-disaccharide, were synthesized with good to excellent yields. PMID- 26676933 TI - A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans. AB - Caloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY 294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild-type worms, but no lifespan effects were observed in eat-2 mutant worms, a genetic model of CR, suggesting that life-extending effects may be acting via CR-related mechanisms. We also treated daf-16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF-16-independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies. PMID- 26676937 TI - Development of an SPME-GC-MS method for the specific quantification of dimethylamine and trimethylamine: use of a new ratio for the freshness monitoring of cod fillets. AB - BACKGROUND: Fish is a highly perishable food, so it is important to be able to estimate its freshness to ensure optimum quality for consumers. The present study describes the development of an SPME-GC-MS technique capable of quantifying both trimethylamine (TMA) and dimethylamine (DMA), components of what has been defined as partial volatile basic nitrogen (PVB-N). This method was used, together with other reference methods, to monitor the storage of cod fillets (Gadus morhua) conserved under melting ice. RESULTS: Careful optimisation enabled definition of the best parameters for extracting and separating targeted amines and an internal standard. The study of cod spoilage by sensory analysis and TVB-N assay led to the conclusion that the shelf-life of cod fillet was between 6 and 7 days. Throughout the study, TMA and DMA were specifically quantified by SPME-GC-MS; the first was found to be highly correlated with the values returned by steam distillation assays. Neither TMA-N nor DMA-N were able to successfully characterise the decrease in early freshness, unlike dimethylamine/trimethylamine ratio (DTR), whose evolution is closely related to the results of sensory analysis until the stage where fillets need to be rejected. CONCLUSION: DTR was proposed as a reliable indicator for the early decrease of freshness until fish rejection. (c) 2015 Society of Chemical Industry. PMID- 26676939 TI - FHL2: a scaffold protein of carcinogenesis, tumour-stroma interactions and treatment response. AB - Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional scaffolding protein regulating signalling cascades and gene transcription. It shuttles between focal adhesions and the nucleus where it signals through direct interaction with a number of proteins including beta-catenin. The multiplicity of molecular pathways affected by FHL2 suggests an important role in several physiological and pathological events. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. In this review we present the current knowledge on the role of FHL2 in carcinogenesis, with emphasis on the digestive tract. We discuss the overexpression of FHL2 in colorectal, gastric and pancreatic cancer, the downregulation in hepatocellular carcinoma and the role of FHL2 in epithelial-mesenchymal transition. We briefly look at the potential role of FHL2 in the tumoural microenvironment and discuss how FHL2 expression and function might influence cancer treatment. Before implementation of FHL2 as a biomarker by pathologists, antibody validation should, however, be carried out. PMID- 26676940 TI - Molecular characterization of DENV-3 circulating during the post-monsoon period of 2013-14 in Delhi, India. PMID- 26676938 TI - Victimization and Biological Stress Responses in Urban Adolescents: Emotion Regulation as a Moderator. AB - Associations between urban adolescents' victimization experiences and biological stress responses were examined, as well as emotion regulation as a moderator of these associations. Data from a 4-wave longitudinal study with a low-income, community-based sample (n = 242; 91 % African American; 57 % female; M = 11.98, SD = 1.56 years at baseline) revealed that victimization, assessed over 3 study waves, was associated with an attenuated cortisol response to a stress interview at the final study wave, indicating that responses of the Hypothalamus-Pituitary Adrenal (HPA) axis were dysregulated. Cortisol responses were moderated by caregiver-reported adolescent emotion regulation, suggesting that this modifiable protective factor that is taught in many school-based prevention programs could help reduce harm associated with HPA axis dysregulation linked to victimization. PMID- 26676941 TI - Application of an M13 bacteriophage displaying tyrosine on the surface for detection of Fe(3+) and Fe(2+) ions. AB - Ferric and ferrous ion plays critical roles in bioprocesses, their influences in many fields have not been fully explored due to the lack of methods for quantification of ferric and ferrous ions in biological system or complex matrix. In this study, an M13 bacteriophage (phage) was engineered for use as a sensor for ferric and ferrous ions via the display of a tyrosine residue on the P8 coat protein. The interaction between the specific phenol group of tyrosine and Fe(3+) / Fe(2+) was used as the sensor. Transmission electron microscopy showed aggregation of the tyrosine-displaying phages after incubation with Fe(3+) and Fe(2+). The aggregated phages infected the host bacterium inefficiently. This phenomenon could be utilized for detection of ferric and ferrous ions. For ferric ions, a calibration curve ranging from 200 nmol/L to 8 MUmol/L with a detection limit of 58 nmol/L was acquired. For ferrous ions, a calibration curve ranging from 800 nmol/L to 8 MUmol/L with a detection limit of 641.7 nmol/L was acquired. The assay was specific for Fe(3+) and Fe(2+) when tested against Ni(2+), Pb(2+), Zn(2+), Mn(2+), Co(2+), Ca(2+), Cu(2+), Cr(3+), Ba(2+), and K(+). The tyrosine displaying phage to Fe(3+) and Fe(2+) interaction would have plenty of room in application to biomaterials and bionanotechnology. PMID- 26676943 TI - Obese type 2 diabetes mellitus patients have higher serum vaspin concentrations. PMID- 26676942 TI - HIV-1 Vpr protein activates the NF-kappaB pathway to promote G2/M cell cycle arrest. AB - Viral protein R (Vpr) plays an important role in the replication and pathogenesis of Human immunodeficiency virus type 1 (HIV-1). Some of the various functions attributed to Vpr, including the induction of G2/M cell cycle arrest, activating the NF-kappaB pathway, and promoting viral reverse transcription, might be interrelated. To test this hypothesis, a panel of Vpr mutants were investigated for their ability to induce G2/M arrest and to activate the NF-kappaB pathway. The results showed that the Vpr mutants that failed to activate NF-kappaB also lost the activity to induce G2/M arrest, which suggests that inducing G2/M arrest via Vpr depends at least partially on the activation of NF-kappaB. This latter possibility is supported by data showing that knocking down the key factors in the NF-kappaB pathway-p65, RelB, IKKalpha, or IKKbeta-partially rescued the G2/M arrest induced by Vpr. Our results suggest that the NF-kappaB pathway is probably involved in Vpr-induced G2/M cell cycle arrest. PMID- 26676944 TI - Fluid mechanics of blood flow in human fetal left ventricles based on patient specific 4D ultrasound scans. AB - The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts. PMID- 26676945 TI - Graphene-Encapsulated Nanosheet-Assembled Zinc-Nickel-Cobalt Oxide Microspheres for Enhanced Lithium Storage. AB - The appropriate combination of hierarchical transition-metal oxide (TMO) micro /nanostructures constructed from porous nanobuilding blocks with graphene sheets (GNS) in a core/shell geometry is highly desirable for high-performance lithium ion batteries (LIBs). A facile and scalable process for the fabrication of 3D hierarchical porous zinc-nickel-cobalt oxide (ZNCO) microspheres constructed from porous ultrathin nanosheets encapsulated by GNS to form a core/shell geometry is reported for improved electrochemical performance of the TMOs as an anode in LIBs. By virtue of their intriguing structural features, the produced ZNCO/GNS core/shell hybrids exhibit an outstanding reversible capacity of 1015 mA h g(-1) at 0.1 C after 50 cycles. Even at a high rate of 1 C, a stable capacity as high as 420 mA h g(-1) could be maintained after 900 cycles, which suggested their great potential as efficient electrodes for high-performance LIBs. PMID- 26676946 TI - A Universal Polymerase Chain Reaction Developer. AB - The versatility of PCR, the gold standard for amplification of DNA targets, is hampered by the laborious, multi-step detection based on gel electrophoresis. We propose a one-step, one-tube method for the rapid (5 min) naked-eye detection of PCR products, based on controlled aggregation of gold nanoparticles. Our method is universal, instrument-free, and ultra-sensitive, as it could detect as low as 0.01 zeptomoles of HIV template DNA in an excess of interfering human genomic DNA. PMID- 26676947 TI - 3,4-Methylenedioxypyrovalerone (MDPV): in vitro mechanisms of hepatotoxicity under normothermic and hyperthermic conditions. AB - Synthetic cathinones have emerged in recreational drug markets as legal alternatives for classical amphetamines. Though currently banned in several countries, 3,4-methylenedioxypyrovalerone (MDPV) is one of the most commonly abused cathinone derivatives worldwide. We have recently reported the potential of MDPV to induce hepatocellular damage, but the underlying mechanisms responsible for such toxicity remain to be elucidated. Similar to amphetamines, a prominent toxic effect of acute intoxications by MDPV is hyperthermia. Therefore, the present in vitro study aimed to provide insights into cellular mechanisms involved in MDPV-induced hepatotoxicity and also evaluate the contribution of hyperthermia to the observed toxic effects. Primary cultures of rat hepatocytes were exposed to 0.2-1.6 mM MDPV for 48 h, at 37 or 40.5 degrees C, simulating the rise in body temperature that follows MDPV intake. Cell viability was measured through the MTT reduction and LDH leakage assays. Oxidative stress endpoints and cell death pathways were evaluated, namely the production of reactive oxygen and nitrogen species (ROS and RNS), intracellular levels of reduced (GSH) and oxidized (GSSG) glutathione, adenosine triphosphate (ATP) and free calcium (Ca(2+)), as well as the activities of caspases 3, 8 and 9, and nuclear morphological changes with Hoechst 33342/PI double staining. At 37 degrees C, MDPV induced a concentration-dependent loss of cell viability that was accompanied by GSH depletion, as one of the first signs of toxicity, observed already at low concentrations of MDPV, with negligible changes on GSSG levels, followed by accumulation of ROS and RNS, depletion of ATP contents and increases in intracellular Ca(2+) concentrations. Additionally, activation of caspases 3, 8, and 9 and apoptotic nuclear morphological changes were found in primary rat hepatocytes exposed to MDPV, indicating that this cathinone derivative activates both intrinsic and extrinsic apoptotic death pathways. The cytotoxic potential of MDPV and all the studied endpoints were markedly aggravated under hyperthermic conditions (40.5 degrees C). In conclusion, these data suggest that MDPV toxicity in primary rat hepatocytes is mediated by oxidative stress, subsequent to GSH depletion and increased ROS and RNS accumulation, mitochondrial dysfunction, and impairment of Ca(2+) homeostasis. Furthermore, the rise in body temperature subsequent to MDPV abuse greatly exacerbates its hepatotoxic potential. PMID- 26676948 TI - Cardiotoxicity screening: a review of rapid-throughput in vitro approaches. AB - Cardiac toxicity represents one of the leading causes of drug failure along different stages of drug development. Multiple very successful pharmaceuticals had to be pulled from the market or labeled with strict usage warnings due to adverse cardiac effects. In order to protect clinical trial participants and patients, the International Conference on Harmonization published guidelines to recommend that all new drugs to be tested preclinically for hERG (Kv11.1) channel sensitivity before submitting for regulatory reviews. However, extensive studies have demonstrated that measurement of hERG activity has limitations due to the multiple molecular targets of drug compound through which it may mitigate or abolish a potential arrhythmia, and therefore, a model measuring multiple ion channel effects is likely to be more predictive. Several phenotypic rapid throughput methods have been developed to predict the potential cardiac toxic compounds in the early stages of drug development using embryonic stem cells- or human induced pluripotent stem cell-derived cardiomyocytes. These rapid throughput methods include microelectrode array-based field potential assay, impedance-based or Ca(2+) dynamics-based cardiomyocytes contractility assays. This review aims to discuss advantages and limitations of these phenotypic assays for cardiac toxicity assessment. PMID- 26676949 TI - In dialogue with an avatar, language behavior is identical to dialogue with a human partner. AB - The use of virtual reality (VR) as a methodological tool is becoming increasingly popular in behavioral research as its flexibility allows for a wide range of applications. This new method has not been as widely accepted in the field of psycholinguistics, however, possibly due to the assumption that language processing during human-computer interactions does not accurately reflect human human interactions. Yet at the same time there is a growing need to study human human language interactions in a tightly controlled context, which has not been possible using existing methods. VR, however, offers experimental control over parameters that cannot be (as finely) controlled in the real world. As such, in this study we aim to show that human-computer language interaction is comparable to human-human language interaction in virtual reality. In the current study we compare participants' language behavior in a syntactic priming task with human versus computer partners: we used a human partner, a human-like avatar with human like facial expressions and verbal behavior, and a computer-like avatar which had this humanness removed. As predicted, our study shows comparable priming effects between the human and human-like avatar suggesting that participants attributed human-like agency to the human-like avatar. Indeed, when interacting with the computer-like avatar, the priming effect was significantly decreased. This suggests that when interacting with a human-like avatar, sentence processing is comparable to interacting with a human partner. Our study therefore shows that VR is a valid platform for conducting language research and studying dialogue interactions in an ecologically valid manner. PMID- 26676950 TI - Using Automated Learning Devices for Monkeys (ALDM) to study social networks. AB - Social network analysis has become a prominent tool to study animal social life, and there is an increasing need to develop new systems to collect social information automatically, systematically, and reliably. Here we explore the use of a freely accessible Automated Learning Device for Monkeys (ALDM) to collect such social information on a group of 22 captive baboons (Papio papio). We compared the social network obtained from the co-presence of the baboons in ten ALDM testing booths to the social network obtained through standard behavioral observation techniques. The results show that the co-presence network accurately reflects the social organization of the group, and also indicate under which conditions the co-presence network is most informative. In particular, the best correlation between the two networks was obtained with a minimum of 40 days of computer records and for individuals with at least 500 records per day. We also show through random permutation tests that the observed correlations go beyond what would be observed by simple synchronous activity, to reflect a preferential choice of closely located testing booths. The use of automatized cognitive testing therefore presents a new way of obtaining a large and regular amount of social information that is necessary to develop social network analysis. It also opens the possibility of studying dynamic changes in network structure with time and in relation to the cognitive performance of individuals. PMID- 26676952 TI - Clinical Recognition of Melanoma in Dermatologists and Nondermatologists. AB - BACKGROUND: The incidence of melanoma is increasing annually in Canada. OBJECTIVES: This retrospective study was designed to assess the ability of physicians of different specialties to accurately recognize melanoma. METHODS: Pathology reports of biopsies submitted to Vancouver Coastal Health with clinical diagnoses of melanoma were reviewed (January to July 2013). The clinical diagnoses made by dermatologists, general practitioners and family physicians, and all other specialists were correlated with the final histopathologic diagnoses. RESULTS: The dermatologists, general practitioners and family physicians, and all other specialists achieved diagnostic accuracies of 24.75%, 3.52%, and 12.75%, respectively. CONCLUSIONS: Although the diagnostic accuracy of dermatologists was significantly better than that the other practitioners, the majority of patients with suspicious skin lesions present to family physicians or general practitioners first. Thus, there is considerable value in providing more training and education to nondermatologists, because it can have a meaningful impact on patient care. PMID- 26676951 TI - Human proximal tubule cells form functional microtissues. AB - The epithelial cells lining the proximal tubules of the kidney mediate complex transport processes and are particularly vulnerable to drug toxicity. Drug toxicity studies are classically based on two-dimensional cultures of immortalized proximal tubular cells. Such immortalized cells are dedifferentiated, and lose transport properties (including saturable endocytic uptake) encountered in vivo. Generating differentiated, organotypic human microtissues would potentially alleviate these limitations and facilitate drug toxicity studies. Here, we describe the generation and characterization of kidney microtissues from immortalized (HK-2) and primary (HRPTEpiC) human renal proximal tubular epithelial cells under well-defined conditions. Microtissue cultures were done in hanging drop GravityPLUSTM culture plates and were characterized for morphology, proliferation and differentiation markers, and by monitoring the endocytic uptake of albumin. Kidney microtissues were successfully obtained by co culturing HK-2 or HRPTEpiC cells with fibroblasts. The HK-2 microtissues formed highly proliferative, but dedifferentiated microtissues within 10 days of culture, while co-culture with fibroblasts yielded spherical structures already after 2 days. Low passage HRPTEpiC microtissues (mono- and co-culture) were less proliferative and expressed tissue-specific differentiation markers. Electron microscopy evidenced epithelial differentiation markers including microvilli, tight junctions, endosomes, and lysosomes in the co-cultured HRPTEpiC microtissues. The co-cultured HRPTEpiC microtissues showed specific uptake of albumin that could be inhibited by cadmium and gentamycin. In conclusion, we established a reliable hanging drop protocol to obtain functional kidney microtissues with proximal tubular epithelial cell lines. These microtissues could be used for high-throughput drug and toxicology screenings, with endocytosis as a functional readout. PMID- 26676953 TI - Merkel Cell Carcinoma With Gastric Metastasis and Review of Literature. AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neoplasm, with a propensity for recurrence and metastasis. Very few cases of metastases to the gastrointestinal tract have been reported in the medical literature. OBJECTIVES: The aim of this study was to report a case of MCC metastasizing to the stomach, its clinical presentation, and its management. METHODS: A PubMed search was made using the following search terms: "Merkel cell carcinoma," "gastric," and "metastasis." RESULTS: The investigators report a case of MCC metastatic to the stomach presenting with melena, syncope, early satiety, increasing fatigue, and unintentional weight loss. The other known cases of gastrointestinal metastasis of MCC are summarized and critically reviewed. CONCLUSIONS: Although MCC spreading to the stomach is exceedingly rare, because of MCC's high recurrence rate and metastatic potential, it should be considered in patients with histories of MCC presenting with recent weight loss, early satiety, and gastrointestinal bleeding. PMID- 26676954 TI - Promoting effect of licorice extract on spermatogonial proliferation and spermatocytes differentiation of neonatal mice in vitro. AB - Licorice (glycyrrhiza uralensis) is known as an herb with detoxication, and it has been widely used in clinical prescription of Oriental herbal medicine. Studies on the effects of licorice in the reproductive system were very rare, especially in spermatogenesis. In order to elucidate the effects of licorice on spermatogonial proliferation and spermatocyte differentiation during neonatal mice spermatogenesis, the organ culture model of testis tissue from neonatal C57BL/6N mice (born 6 d) was established. Then, in the presence of licorice extract (LE), the proliferation activity of spermatogonia was identified with the positive rate quantitative analysis of 5-bromo-2-deoxyuridine (BrdU) and anti proliferating cell nuclear antigen (PCNA) antibody by immunohistochemical staining. The results showed that, compared to the control group, the percentage of positive cells by BrdU staining enhanced dramatically and that the expression of PCNA protein increased significantly in the spermatogonia from the LE group and showed a concentration-dependent manner (P < 0.05). This indicated that the LE can significantly promote the proliferation of spermatogonia in the spermatogenesis of neonatal mice. Furthermore, proteins related to spermatocyte differentiation, synaptonemal complex protein 3 (SCP3) and meiotic recombinant protein Spo11, were detected by immunohistochemical staining. The results showed that the differentiated spermatocyte in the LE group was significantly increased compared with that of the control group and showed a concentration-dependent manner (P < 0.05). The above results suggested that the LE can significantly accelerate the proliferation of spermatogonia and the differentiation of spermatocytes in the testicular tissue of the neonatal mice, which may be a potential drug for male infertility. PMID- 26676956 TI - Introduction of positron emission tomography into the Western Norwegian Health Region: Regional balance in resource utilization from 2009 to 2014. AB - BACKGROUND: The aim was to compare resource utilization across the four health trusts within the Western Norway Regional Health Authority since the establishment of positron emission tomography (PET) at Haukeland University Hospital in Bergen in 2009. METHODS: Metadata from all PET examinations from 2009 to 2014 were automatically imported from the PET centre's central production database into a custom-developed database system, MDCake. A PET examination was defined as a procedure based on a single injection of radioactive tracer. The patients' place of residence and tentative diagnosis were coded based on the available clinical information. RESULTS: The total number of PET examinations increased from 293 in 2009 to 1616 in 2014. The number of PET examinations per year increased across all diagnostic groups, but plateaued for lung cancer, gastrointestinal cancer and malignant melanoma since 2013. The number of examinations per capita was evenly distributed between the three northern health trusts with an average of 1260 PET studies per million inhabitants in 2014. However, patients residing in the most southerly health trust received between 44% (2010) and 27% (2014; P<0.001, repeated measures ANOVA) fewer examinations per capita per year. CONCLUSION: Centralized PET in the Western Norwegian health region meets the current clinical demand for patients residing in the three northern health trusts while patients from the most southern health trust receive approximately 30% fewer PET examinations. Access to specialized health care should be monitored routinely in order to identify inequalities in referral patterns and resource utilization. PMID- 26676958 TI - Fine tuning of graphene properties by modification with aryl halogens. AB - Graphene and its derivatives belong to one of the most intensively studied materials. The radical reaction using halogen derivatives of arene-diazonium salts can be used for effective control of graphene's electronic properties. In our work we investigated the influence of halogen atoms (fluorine, chlorine, bromine and iodine) as well as their position on the benzene ring towards the electronic and electrochemical properties of modified graphenes. The electronegativity as well as the position of the halogen atoms on the benzene ring has crucial influence on graphene's properties due to the inductive and mesomeric effects. The results of resistivity measurement are in good agreement with the theoretical calculations of electron density within chemically modified graphene sheets. Such simple chemical modifications of graphene can be used for controllable and scalable synthesis of graphene with tunable transport properties. PMID- 26676955 TI - MicroRNA-764-3p regulates 17beta-estradiol synthesis of mouse ovarian granulosa cells by targeting steroidogenic factor-1. AB - Previous studies have reported that microRNA-764-3p (miR-764-3p) is one of the most up-regulated microRNAs (miRNAs) in TGF-beta1-stimulated mouse ovarian granulosa cells. However, little is known about the roles and mechanisms of miR 764-3p in granulosa cell function during follicular development. In this study, we found that overexpression of miR-764-3p inhibited 17beta-estradiol (E2) synthesis of granulosa cells through directly targeting steroidogenic factor-1 (SF-1). MiR-764-3p inhibited SF-1 by affecting its messenger RNA (mRNA) stability, which subsequently suppressed the expression levels of Cyp19a1 gene (aromatase, a downstream target of SF-1). In addition, SF-1 was involved in regulation of miR-764-3p-mediated Cyp19a1 expression in granulosa cells which contributed, at least partially, to the effects of miR-764-3p on granulosa cell E2 release. These results suggest that miR-764-3p functions to decrease steroidogenesis by targeting SF-1, at least in part, through inactivation of Cyp19a1. Taken together, our data provide mechanistic insights into the roles of miR-764-3p on E2 synthesis. Understanding of potential miRNAs affecting estrogen synthesis will help to diagnose and treat steroid-related diseases. PMID- 26676957 TI - Legal claims in Scottish National Health Service dermatology departments, 2002 2013. PMID- 26676959 TI - Shear stress, arterial identity and atherosclerosis. AB - In the developing embryo, the vasculature first takes the form of a web-like network called the vascular plexus. Arterial and venous differentiation is subsequently guided by the specific expression of genes in the endothelial cells that provide spatial and temporal cues for development. Notch1/4, Notch ligand delta-like 4 (Dll4), and Notch downstream effectors are typically expressed in arterial cells along with EphrinB2, whereas chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and EphB4 characterise vein endothelial cells. Haemodynamic forces (blood pressure and blood flow) also contribute importantly to vascular remodelling. Early arteriovenous differentiation and local blood flow may hold the key to future inflammatory diseases. Indeed, despite the fact that atherosclerosis risk factors such as smoking, hypertension, hypercholesterolaemia, and diabetes all induce endothelial cell dysfunction throughout the vasculature, plaques develop only in arteries, and they localise essentially in vessel branch points, curvatures and bifurcations, where blood flow (and consequently shear stress) is low or oscillatory. Arterial segments exposed to high blood flow (and high laminar shear stress) tend to remain plaque free. These observations have led many to investigate what particular properties of arterial or venous endothelial cells confer susceptibility or protection from plaque formation, and how that might interact with a particular shear stress environment. PMID- 26676960 TI - Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy. AB - DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11 negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients. PMID- 26676961 TI - Beneficial health characteristics of native and hydrolysed konjac (Amorphophallus konjac) glucomannan. AB - The impact of ingesting glucomannans on health is not limited to colonic-focused fermentation into short-chain fatty acids (SCFAs), which might have some local health benefits; it also helps in treating disease states and enhancing the body's immune system, both within the gut and in/on other parts of the body. The local and systemic roles of hydrolysed glucomannans, especially konjac glucomannans, in the mouth, oesophagus, stomach, small intestine, large intestine, gut-associated lymphoid tissue (GALT), skin and vagina, are highlighted. Therapeutic applications are discussed. (c) 2015 Society of Chemical Industry. PMID- 26676962 TI - Copper-free Sandmeyer cyanation of arenediazonium o-benzenedisulfonimides. AB - Arene and heteroarenediazonium o-benzenedisulfonimides can be used as efficient reagents in Sandmeyer cyanation. This work reports such reactions carried out by us under very mild conditions using tetrabutyl ammonium cyanide as a safe cyanide source and, interestingly, without the need for a Cu catalyst. The reactions have given rise to aryl nitriles in good yields (25 examples, average yield 75%). A good amount of o-benzenedisulfonimide was recovered from each reaction and then reused to prepare other salts. Mechanistic insights have allowed us to highlight the fundamental role of the o-benzenedisulfonimide anion as an electron transfer agent. PMID- 26676963 TI - Getting Incentives Right? The Impact of Hospital Capitation Payment in Vietnam. AB - This paper evaluates the impact on cost and utilization of a shift from fee-for service to capitation payment of district hospitals by Vietnam's social health insurance agency. Hospital fixed effects analysis suggests that capitation leads to reduced costs. Hospitals also increased service provision to the uninsured who continue to pay out-of-pocket on a fee-for-service basis. The study points to the need to anticipate unintended effects of payment reforms, especially in the context of a multiple purchaser system. Copyright (c) The World Bank Health Economics (c) 2015 John Wiley & Sons, Ltd. PMID- 26676964 TI - Maturity onset diabetes of the young 5 accompanied by duodenal cysts. PMID- 26676965 TI - Skin-Inspired Haptic Memory Arrays with an Electrically Reconfigurable Architecture. AB - Skin-inspired haptic-memory devices, which can retain pressure information after the removel of external pressure by virtue of the nonvolatile nature of the memory devices, are achieved. The rise of haptic-memory devices will allow for mimicry of human sensory memory, opening new avenues for the design of next generation high-performance sensing devices and systems. PMID- 26676966 TI - Kindlin-2 siRNA inhibits vascular smooth muscle cell proliferation, migration and intimal hyperplasia via Wnt signaling. AB - It is known that vascular smooth muscle cell (VSMC) proliferation and migration leads to intimal hyperplasia in cases of atherosclerosis and restenosis. In the present study, we investigated the effects of kindlin-2 on VSMC proliferation, migration and intimal hyperplasia, and the underlying mechanisms. The left common carotid artery of Sprague-Dawley rats were subjected to balloon injury in order to induce intimal hyperplasia, and then transfected with kindlin-2 small interfering RNA (siRNA) lentivirus or negative control siRNA lentivirus. We noted that the degree of intimal hyperplasia 4 weeks after balloon injury was significantly reduced in arteries transfected with kindlin-2 siRNA lentivirus (P<0.05). In vitro, kindlin-2 siRNA suppressed VSMC proliferation and migration induced by Wnt3a (100 ng/ml). Western blot analyses and RT-qPCR revealed that kindlin-2 regulated Wnt/beta-catenin signaling and thereby modulated the expression of beta-catenin target genes, including c-myc and cyclin D1. This study demonstrated that kindlin-2 plays a critical role in VSMC proliferation, migration and intimal hyperplasia via Wnt signaling. Therefore, blocking the activity of kindlin-2 represents a novel therapeutic strategy for vascular injury. PMID- 26676967 TI - Redesigning the stereospecificity of tyrosyl-tRNA synthetase. AB - D-Amino acids are largely excluded from protein synthesis, yet they are of great interest in biotechnology. Unnatural amino acids have been introduced into proteins using engineered aminoacyl-tRNA synthetases (aaRSs), and this strategy might be applicable to D-amino acids. Several aaRSs can aminoacylate their tRNA with a D-amino acid; of these, tyrosyl-tRNA synthetase (TyrRS) has the weakest stereospecificity. We use computational protein design to suggest active site mutations in Escherichia coli TyrRS that could increase its D-Tyr binding further, relative to L-Tyr. The mutations selected all modify one or more sidechain charges in the Tyr binding pocket. We test their effect by probing the aminoacyl-adenylation reaction through pyrophosphate exchange experiments. We also perform extensive alchemical free energy simulations to obtain L-Tyr/D-Tyr binding free energy differences. Agreement with experiment is good, validating the structural models and detailed thermodynamic predictions the simulations provide. The TyrRS stereospecificity proves hard to engineer through charge altering mutations in the first and second coordination shells of the Tyr ammonium group. Of six mutants tested, two are active towards D-Tyr; one of these has an inverted stereospecificity, with a large preference for D-Tyr. However, its activity is low. Evidently, the TyrRS stereospecificity is robust towards charge rearrangements near the ligand. Future design may have to consider more distant and/or electrically neutral target mutations, and possibly design for binding of the transition state, whose structure however can only be modeled. PMID- 26676969 TI - Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease. AB - INTRODUCTION: Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. MATERIAL AND METHODS: There were 98 children (mean age: 13 +/- 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 +/- 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. RESULTS: FEV1, FEV1/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. CONCLUSIONS: Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality. PMID- 26676970 TI - Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication. AB - Gliomas are the most common type of primary brain tumor. Using current standard treatment regimens, the prognosis of patients with gliomas remains poor, which is predominantly due to the resistance of glioma cells to chemotherapy. The organ microenvironment has been implicated in the pathogenesis and survival of tumor cells. Thus, the aim of the present study was to test the hypothesis that astrocytes (the housekeeping cells of the brain microenvironment) may protect glioma cells from chemotherapy and to investigate the underlying mechanism. Immunofluorescent and scanning electron microscopy demonstrated that glioma cells were surrounded and infiltrated by activated astrocytes. In vitro co-culture of glioma cells with astrocytes significantly reduced the cytotoxic effects on glioma cells caused by various chemotherapeutic agents, as demonstrated by fluorescein isothiocyanate-propidium iodide flow cytometry. Transwell experiments indicated that this protective effect was dependent on physical contact and the gap junctional communication (GJC) between astrocytes and glioma cells. Microarray expression profiling further revealed that astrocytes upregulated the expression levels of various critical survival genes in the glioma cells via GJC. The results of the present study indicated that the organ microenvironment may affect the biological behavior of tumor cells and suggest a novel mechanism of resistance in glioma cells, which may be of therapeutic relevance clinically. PMID- 26676968 TI - Pigment-Synthesizing Melanocytic Neoplasm With Protein Kinase C Alpha (PRKCA) Fusion. AB - IMPORTANCE: Melanocytic neoplasms with prominent pigment synthesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low grade malignant melanocytic tumors in which the molecular profile and exact histologic classification are not established. Tumors with these characteristics rarely occur as congenital lesions. We performed genomic analysis of a congenital pigment synthesizing melanocytic neoplasm with indeterminate biological potential. OBSERVATIONS: The patient was a 5-month-old girl presenting with a 6 cm protuberant scalp mass, which had doubled in size since birth. Histologic examination showed heavily pigmented intradermal proliferation of large, epithelioid melanocytes with mild cytologic atypia, low mitotic activity, focal necrosis, and ulceration. RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4(ATP2B4)-protein kinase C-alpha (PRKCA) fusion transcript. The fusion resulted in an in-frame linkage of the PRKCA catalytic domain with the N-terminal of ATP2B4 and high expression of the PRKCA kinase domain. Break-apart fluorescence in situ hybridization showed PRKCA rearrangement, and reverse transcriptase-polymerase chain reaction confirmed the presence of the fusion transcript. The patient was alive and well, with no evidence of recurrence, at the 1-year follow-up. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of PRKCA fusions in melanocytic neoplasms. Future studies need to determine the frequency of PRKCA fusions in pigment-synthesizing melanocytic neoplasms. PMID- 26676971 TI - An assessment of West African seahorses in fisheries catch and trade. AB - This study provides the first assessment of a heavily traded West African seahorse species, Hippocampus algiricus, and the first information on short snouted seahorse Hippocampus hippocampus biology in Africa. A total of 219 seahorses were sampled from fisher catch in Senegal and The Gambia, with estimated height at reproductive activity for H. algiricus (161 mm) larger than mean +/- S.D. catch height (150 +/- 31 mm). Catch composition, height at reproductive activity and potential biases in fishery retention are discussed with regard to the current Convention on International Trade of Endangered Species (CITES) guidelines. PMID- 26676973 TI - Drug resistance and tropism as markers of the dynamics of HIV-1 DNA quasispecies in blood cells of heavily pretreated patients who achieved sustained virological suppression. AB - OBJECTIVES: The objective of this study was to address the dynamics of archived resistant quasispecies in cell-associated HIV-1 DNA over time in heavily ART experienced patients with currently suppressed plasma HIV-1 RNA. METHODS: Longitudinal ultra-deep sequencing (UDS) analysis of reverse transcriptase, protease and V3 Env regions was performed on blood-cell-associated HIV-1 DNA samples. Drug-resistance-associated mutations (DRAMs) and tropism were interpreted using the ANRS and Geno2Pheno algorithms. We analysed frozen blood cells from patients enrolled in the INNOVE and ANRS 123 ETOILE studies who achieved sustained viral suppression after salvage optimized ART (SOT). RESULTS: Samples were available at baseline and 6 and >=12 months after SOT initiation in 10 patients. V3 loop sequences displayed wide intra-individual dynamics over time. Viral variants harbouring DRAMs exhibited three non-exclusive scenarios. First, when SOT exerted the same selective pressure as previous failing regimens, some viral quasispecies still harboured the same DRAMs at the same level as at the time of virological failure. Thus, as DRAMs were mostly associated with the same viral variant, variants with a complete resistance pattern remained archived. Second, some viral variants harbouring DRAMs were no longer detected over time when SOT consisted of new antiretroviral classes or had resistance profiles distinct from those of previous failing regimens. Third, variants with new DRAMs associated with SOT emerged in blood cells during follow-up despite sustained virological control. CONCLUSIONS: Using longitudinal UDS analysis and focusing on DRAMs and tropism as markers, we demonstrated that, despite sustained virological control, archived HIV-1 DNA quasispecies continued to evolve. PMID- 26676972 TI - Identification of miR-15b as a transformation-related factor in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with a poor prognosis. It is characterized by the t(11;14)(q13;q32) translocation, resulting in over-expression of CCND1. Morphologically, MCL is categorised into two types: classical MCL (cMCL) and aggressive MCL (aMCL), with a proportion of cMCL progressing to develop into aMCL. miRNAs are currently considered to be important regulators for cell behavior and are deregulated in many malignancies. Although several genetic alterations have been implicated in the transformation of cMCL to aMCL, the involvement of miRNAs in transformation is not known. In an effort to identify the miRNAs related to the transformation of MCL, miRNA microarray analyses were used for cMCL and aMCL cases. These analyses demonstrated significant differences in the expression of seven microRNAs based on a t-test (p value <0.05); miR-15b was greatly upregulated in aMCL. Locked nucleic acid in situ hybridization showed increased staining of miR-15b in formalin-fixed paraffin-embedded sections of aMCL. These results correlated well with the microRNA microarray analysis. Although the molecular functions of miR-15b are largely unknown, it has been found to be associated with the cell cycle and apoptosis. However, the physiological significance of increased miR-15b in MCL is still unknown. Our present findings suggest that the upregulated expression of miR-15b is likely to play an important role in the trans-formation of cMCL to aMCL. PMID- 26676974 TI - Organic Carbonates: Efficient Extraction Solvents for the Synthesis of HMF in Aqueous Media with Cerium Phosphates as Catalysts. AB - We describe a process for the selective conversion of C6 -polyols into 5 hydroxymethylfurfural (5-HMF) in biphasic systems of organic carbonate/water (OC/W), with cerium(IV) phosphates as catalysts. Different reaction parameters such as the OC/W ratio, catalyst loading, reaction time, and temperature, were investigated for the dehydration of fructose. Under the best reaction conditions, a yield of 67.7 % with a selectivity of 93.2 % was achieved at 423 K after 6 h of reaction using [(Ce(PO4)1.5 (H2 O)(H3 O)0.5 (H2 O)0.5)] as the catalyst. A maximum yield of 70 % with the same selectivity was achieved after 12 h. At the end of the reaction, the catalyst was removed by centrifugation, the organic phase was separated from water and evaporated in vacuo (with solvent recovery), and solid 5-HMF was isolated (purity >99 %). The recovery and reuse of the catalyst and the relationship between the structure of the OC and the efficiency of the extraction are discussed. The OC/W system influences the lifetime of the catalysts positively compared to only water. PMID- 26676975 TI - The Amyloid Fibril-Forming Properties of the Amphibian Antimicrobial Peptide Uperin 3.5. AB - The amphibian skin is a vast resource for bioactive peptides, which form the basis of the animals' innate immune system. Key components of the secretions of the cutaneous glands are antimicrobial peptides (AMPs), which exert their cytotoxic effects often as a result of membrane disruption. It is becoming increasingly evident that there is a link between the mechanism of action of AMPs and amyloidogenic peptides and proteins. In this work, we demonstrate that the broad-spectrum amphibian AMP uperin 3.5, which has a random-coil structure in solution but adopts an alpha-helical structure in membrane-like environments, forms amyloid fibrils rapidly in solution at neutral pH. These fibrils are cytotoxic to model neuronal cells in a similar fashion to those formed by the proteins implicated in neurodegenerative diseases. The addition of small quantities of 2,2,2-trifluoroethanol accelerates fibril formation by uperin 3.5, and is correlated with a structural stabilisation induced by this co-solvent. Uperin 3.5 fibril formation and the associated cellular toxicity are inhibited by the polyphenol (-)-epigallocatechin-3-gallate (EGCG). Furthermore, EGCG rapidly dissociates fully formed uperin 3.5 fibrils. Ion mobility-mass spectrometry reveals that uperin 3.5 adopts various oligomeric states in solution. Combined, these observations imply that the mechanism of membrane permeability by uperin 3.5 is related to its fibril-forming properties. PMID- 26676976 TI - Maternal and Child Health in Mongolia at 3 Years After Childbirth: A Population Based Cross-Sectional Descriptive Study. AB - OBJECTIVES: In recent years Mongolia has made great advances towards Millennium Development Goals to reduce maternal and child mortality, however few studies have investigated maternal and child health status several years after childbirth. Our study aims to describe priority health issues in maternal and child health in Mongolia 3 years after childbirth, and key areas requiring further health policy development. METHODS: We conducted a population-based cross sectional study in Bulgan province, Mongolia. Participants were women who gave birth in 2010 and lived in Bulgan in 2013, and their children who were almost 3 years of age. Data was collected using structured interviews, self-administered questionnaires, transcribed records from the Maternal and Child Health Handbook, anthropometric measurements, and a developmental assessment tool. RESULTS: Data was obtained from 1,019 women and 1,013 children (recovery rate: 94.1 %). Among women, 171 (17.2 %) were obese and had an average body mass index (BMI) of 25.7, 40 (4.4 %) experienced intimate partner violence (IPV) and 356 (36.2 %) reported urinary incontinence in the past month. Among children, 110 (10.8 %) were assessed as at risk of developmental delay, 131 (13.1 %) were overweight or obese, burns accounted for the highest number of serious accidents at 173 (17.0 %) while lower respiratory tract infections (LRTIs) were the most frequent cause of pediatric hospitalization. CONCLUSIONS: for Practice Further development in health policy is required in Mongolia to target the significant health challenges of obesity, IPV, and urinary incontinence in women, and obesity, development delay, burns, and LRTIs in children. PMID- 26676977 TI - Maternity Leave Access and Health: A Systematic Narrative Review and Conceptual Framework Development. AB - Background Maternity leave is integral to postpartum maternal and child health, providing necessary time to heal and bond following birth. However, the relationship between maternity leave and health outcomes has not been formally and comprehensively assessed to guide public health research and policy in this area. This review aims to address this gap by investigating both the correlates of maternity leave utilization in the US and the related health benefits for mother and child. Methods We searched the peer-reviewed scholarly literature using six databases for the years 1990 to early 2015 and identified 37 studies to be included in the review. We extracted key data for each of the included studies and assessed study quality using the "Weight of the Evidence" approach. Results The literature generally confirms a positive, though limited correlation between maternity leave coverage and utilization. Likewise, longer maternity leaves are associated with improved breastfeeding intentions and rates of initiation, duration and predominance as well as improved maternal mental health and early childhood outcomes. However, the literature points to important disparities in access to maternity leave that carry over into health outcomes, such as breastfeeding. Synthesis We present a conceptual framework synthesizing what is known to date related to maternity leave access and health outcomes. PMID- 26676978 TI - Electronic Medical Record Use and Maternal and Child Care and Health. AB - OBJECTIVES: To evaluate effects of EHR adoption and use during pregnancy on maternal and child health care utilization and health among pregnant mothers and their infants. METHODS: The study population was comprised of all Medicaid insured pregnant women who delivered a singleton birth in Michigan between 1/1/2009 and 12/31/2012 and their infants (N = 226,558). Linked data included birth records, maternal and infant medical claims, and EHR adoption, implementation, upgrading and meaningful use data. Pre-post comparisons with a control group (difference-in-difference) took advantage of a natural experiment of EHR adoption and use among providers in Michigan. Women and infants who received care from providers who adopted and used EHR were compared with those who received care from other providers, in a quasi-experimental framework. RESULTS: Over 34 % of all women in the analytic sample received perinatal care from providers who adopted and used EHR. Multivariate regressions indicate that women who received prenatal care mainly from a provider who adopted and used EHR were more likely to have any well-child visits (0.05, p = 0.04), and the appropriate number of well-child visits during the first year of life (0.03, p < 0.01). CONCLUSIONS: The findings of this study are consistent with EHR adoption and use supporting improved child health care utilization. The findings have the potential to provide Medicaid and other healthcare program officials with evidence of the potential gains to be derived from EHRs for vulnerable low-income women and infants. PMID- 26676979 TI - The Influence of Treatment Position (Prone vs. Supine) on Clip Displacement, Seroma, Tumor Bed and Partial Breast Target Volumes: Comparative Study. AB - To analyse the displacement of surgical clips in prone (Pr) position and assess the consequences on target volumes and integral dose of partial breast irradiation (PBI). 30 post-lumpectomy breast cancer patients underwent CT imaging in supine (Su) and Pr. Clip displacements were measured by the distances from the clips to a common fix bony reference point. On each dataset, the tumour bed (TB = clips +/- seroma), clinical target volume (CTV = TB + 1.5 cm) and planning target volumes (PTV = CTV + 1 cm) for PBI were determined and the volume pairs were compared. Furthermore estimation of integral dose ratio (IDR) within the breast from tangential treatment was performed as the ratio of the irradiated breast volume and the volume encompassing all clips. Clips close to the chest wall (CW) in Su showed significantly less displacement in Pr. The mean volumes of seroma, CTV and PTV were significantly higher in Pr than in Su. The PTV volume difference (Pr-Su) was significantly higher in patients with presence of seroma, deep clips and TB location in the superior-internal-quadrant (SIQ) and at the junction of superior quadrants (jSQ). In a multivariate analysis two factors remained significant: seroma and TB localization in SIQ-jSQ. The IDR was significantly larger in Su than in Pr (7.6 vs. 4.1 p < 0.01). Clip displacements varied considerably with respect to their relative position to the CW. In selected patients Pr position potentially leads to a significant increase in target volumes of PBI. Tangential beam arrangement for PBI should be avoided, not only in Su but in Pr as well in case of clip-based target volume definition. PMID- 26676980 TI - As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma. AB - BACKGROUND: Cysteine/histidine-rich 1 (CYHR1) was first discovered in a yeast two hybrid screen with murine galectin-3, and no previous reports have described a relationship between the CYHR1 gene and human cancer. The current study evaluated the role and significance of CYHR1 in esophageal cancer. METHODS: The human esophageal squamous cell carcinoma (ESCC) cell line TE-8 and the CYHR1 knock-down cell line TE-8/small interfering (si)-CYHR1 were used for in vitro and in vivo assays. For clinical study, ESCC tissues (n = 104) were used. RESULTS: Compared with parental cells, TE-8/si-CYHR1 cells had suppressed proliferation and invasion activities. In the in vivo assay, the tumors from TE-8 cells treated with si-CYHR1 had abrogated tumorigenicity. In the clinical study, the expression of CYHR1 mRNA was associated with lymph node metastasis and stage and shown to be an independent prognostic factor. CONCLUSIONS: As the findings show, CYHR1 may represent not only a valuable prognostic marker but also a therapeutic target for ESCC patients. PMID- 26676981 TI - Lobular Neoplasia: Another Reset in Management? PMID- 26676982 TI - N-acetylcysteine decreased nicotine reward-like properties and withdrawal in mice. AB - RATIONALE: N-acetylcysteine can increase extrasynaptic glutamate and reduce nicotine self-administration in rats and smoking rates in humans. OBJECTIVES: The aim of this study was to determine if N-acetylcysteine modulates the development of nicotine place conditioning and withdrawal in mice. METHODS: N-acetylcysteine was given to nicotine-treated male ICR mice. Experiment 1: reward-like behavior. N-acetylcysteine (0, 5, 15, 30, or 60 mg/kg, i.p.) was given 15 min before nicotine (0.5 mg/kg, s.c.) or saline (10 ml/kg, s.c.) in an unbiased conditioned place preference (CPP) paradigm. Conditioning for highly palatable food served as control. Experiment 2: spontaneous withdrawal. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on anxiety-like behavior, somatic signs, and hyperalgesia was measured 18-24 h after continuous nicotine (24 mg/kg/day, 14 days). Experiment 3: mecamylamine-precipitated, withdrawal-induced aversion. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on mecamylamine (3.5 mg/kg, i.p.)-precipitated withdrawal was determined after continuous nicotine (24 mg/kg, i.p., 28 days) using the conditioned place aversion (CPA) paradigm. RESULTS: Dose-related reductions in the development of nicotine CPP, somatic withdrawal signs, hyperalgesia, and CPA were observed after N-acetylcysteine pretreatment. No effect of N-acetylcysteine was found on palatable food CPP, anxiety-like behavior, or motoric capacity (crosses between plus maze arms). Finally, N-acetylcysteine did not affect any measure in saline-treated mice at doses effective in nicotine-treated mice. CONCLUSIONS: These are the first data suggesting that N-acetylcysteine blocks specific mouse behaviors associated with nicotine reward and withdrawal, which adds to the growing appreciation that N acetylcysteine may have high clinical utility in combating nicotine dependence. PMID- 26676984 TI - Carcinoma Cuniculatum of the Foot Invading the Bone Mimicking a Pseudo Epitheliomatous Reaction to an Acute Osteomyelitis. AB - Carcinoma cuniculatum is a rare variant of squamous cell carcinoma. The clinical presentation is usually a non-verrucous exophytic plaque or tumor of the plantar region with a penetration in the deep tissues. Histological examination shows a proliferation of well-differentiated keratinocytes. We describe a patient affected by a slowly enlarging tumoral lesion overlying the fifth metatarsum of the left foot. Clinical examination and radiological investigations suggested a chronic osteomyelitis and a first histological examination of a punch biopsy was suggestive of a pseudo-epitheliomatous hyperplasia. The patient underwent several cycles with systemic antibiotics without improvement. Finally, the fifth metatarso was amputated and the skin lesion was completely removed. The histological examination of the whole operatory mass allowed a diagnosis of carcinoma cuniculatum invading the bone. PMID- 26676985 TI - Prevalence, clinical presentation, prognosis, and outcome of 17 dogs with spinal shock and acute thoracolumbar spinal cord disease. AB - OBJECTIVE: To describe the prevalence, signalment, clinical features, etiology, and outcome in dogs with acute thoracolumbar disease and suspected spinal shock. DESIGN: Retrospective clinical case study (2005-2010). SETTING: Private specialty practice. ANIMALS: Medical records of 263 dogs with thoracolumbar spinal magnetic resonance imaging were reviewed. If decreased or absent withdrawal reflexes were present in 1 or both pelvic limbs, in the absence of a spinal lesion in the lumbosacral intumescence, dogs were diagnosed with spinal shock. Dogs with suspected or confirmed spinal neoplasia, myelomalacia, or meningomyelitis were excluded. Seventeen of 263 dogs (6%) met inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracic lesions were significantly more likely to result in spinal shock when compared to lumbar lesions (P = 0.03). Fibrocartilaginous embolism was the most commonly diagnosed etiology (7 of 17 dogs), and was more common in the thoracic spine compared to in the lumbar spine (P = 0.10). Six of 17 dogs (35%) were diagnosed with intervertebral disk herniation; 4 of 17 dogs (24%) with suspected acute noncompressive nucleus pulposus extrusion. Two dogs were lost to follow-up. Fourteen of 15 (93%) dogs had improved or normal reflexes by 60 days post injury. CONCLUSIONS: Although the prevalence of spinal shock was low, it should be considered in any dog presenting with an acute history of thoracolumbar spinal injury with reduced or absent reflexes in the pelvic limbs. The presence of spinal shock should not dissuade a veterinarian from pursuing appropriate diagnostic testing and therapy for the underlying etiology. PMID- 26676986 TI - A clinic devoted to peer victimization in special needs children. PMID- 26676983 TI - Ventral tegmental area dopamine revisited: effects of acute and repeated stress. AB - Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression. PMID- 26676988 TI - Loss of imprinting of IGF2 in fibroadenomas and phyllodes tumors of the breast. AB - Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) is thought to be implicated in the pathogenesis of some tumors by upregulating IGF2 mRNA but its role in the pathogenesis of fibroadenomas (FAs) and phyllodes tumors (PTs) of the breast is yet to be studied. LOI of IGF2 was investigated in 25 FAs and 17 PTs which were heterozygous for Apa I polymorphism, and was found to be present in 13 FAs and 12 PTs. IGF2 mRNA expression was more upregulated in FAs and PTs than in paired surrounding normal tissues and laser microdissection showed that IGF2 mRNA expression was significantly higher in the stromal than the epithelial cells. LOI was not associated with upregulation of IGF2 mRNA, nor were MED12 mutations and methylation status of the differentially methylated region 0 (DMR0) of IGF2. These results demonstrate that IGF2 mRNA expression is more upregulated in FAs and PTs than in normal tissues, especially in their stromal cells, but such an upregulation is not related to LOI of IGF2, and that hypomethylation of DMR0 is unlikely to be involved in induction of LOI. PMID- 26676987 TI - Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling. AB - MAIN CONCLUSION: A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post-transcriptional regulation governed by miRNAs and their targets in a naturally stress-tolerant model crop. PMID- 26676989 TI - Heat Shock Protein member A2 forms a stable complex with angiotensin converting enzyme and protein disulfide isomerase A6 in human spermatozoa. AB - STUDY HYPOTHESIS: Given the importance of the chaperone Heat Shock Protein A2 (HSPA2) in the regulation of male fertility, this study aimed to identify and characterize additional proteins that may rely on the activity of this chaperone in human spermatozoa. STUDY FINDING: In view of the findings in this study we propose that angiotensin converting enzyme (ACE) and protein disulfide isomerase A6 (PDIA6) are novel interacting proteins of HSPA2 and that this multimeric complex may participate in key elements of the fertilization cascade. WHAT IS KNOWN ALREADY: The molecular chaperone HSPA2 plays a pivotal role in the remodelling of the sperm surface during capacitation. Indeed, human spermatozoa that are deficient in HSPA2 protein expression lack the ability to recognize human oocytes, resulting in repeated IVF failure in a clinical setting. Moreover, our recent work has shown that defective HSPA2 function induced by oxidative stress leads to the aberrant surface expression of one of its interacting proteins, arylsulfatase A, and thus contributes to a loss of sperm-zona pellucida adhesion. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Human spermatozoa were collected from fertile donors, capacitated and prepared for Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) analysis. Protein complexes resolved via BN-PAGE were excised and their constituents were identified using mass spectrometry. The interactions between ACE, PDIA6 and HSPA2 were then confirmed using immunoprecipitation and proximity ligation assays and the localization of these proteins was assessed in isolated spermatozoa and commercially available human testis tissue sections. Finally, pharmacological inhibition of ACE was performed to assess the role of ACE in human sperm capacitation. MAIN RESULTS AND THE ROLE OF CHANCE: Herein we have identified ACE and PDIA6 as potential HSPA2 interacting proteins and shown that this assemblage resides in membrane raft microdomains located in the peri-acrosomal region of the sperm head. Additionally, the surface expression of PDIA6, but not ACE, was shown to be dynamically regulated during sperm capacitation and, like that of previously characterized HSPA2-interacting proteins, this surface expression proved vulnerable to oxidative stress. In terms of the functional significance of this protein complex, pharmacological inhibition of ACE significantly reduced the ability of human spermatozoa to undergo an agonist induced acrosome reaction (P < 0.01). LIMITATIONS, REASONS FOR CAUTION: While these results provide a descriptive analysis of the PDIA6/ACE/HSPA2 complex, this study provides the impetus for further investigation into the role of PDIA6 and ACE in human sperm function. WIDER IMPLICATIONS OF THE FINDINGS: As our research group, and others, have shown that HSPA2 is compromised in the spermatozoa of men with oocyte recognition defects, the characterization of these HSPA2-interacting proteins provides important insight into the complexity of the cellular pathways that may be affected in the spermatozoa of infertile individuals. LARGE SCALE DATA: Large scale proteomics data can be accessed through the Proteomics Identifications Database (PRIDE). STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Health and Medical Research Council. Grant # APP1046346. The authors have no competing interests to declare. PMID- 26676990 TI - Phytogeographic patterns of the Atlantic Forest in the Rio Doce River Basin, the dart versus arrow debate, and quorum sensing in bacteria. PMID- 26676991 TI - A new index for assessing the value of importance of species--VIS. AB - Phytosociological analysis in native forests is performed considering the horizontal and vertical structure of the studied population, whose most expressive parameters are the density, dominance, frequency, value of coverage and value of importance of species. Many phytosociological studies include a value of importance of species calculated by adding density, dominance and frequency, in their relative forms, however, this estimator is a mathematical impropriety because the result is a sum of indexes and does not express the true meaning of species' value. This is because the estimator is still influenced predominantly by the density of occurrence of species and cannot capture the relevant hierarchical participation of emerging species that occur with low density in the biocoenosis. In this work, we propose a new index to characterize the value of importance of species based on the hierarchy and spatial absolute probability of the species in the biocoenosis, illustrated with data from a forest fragment of semideciduous tropical forest located in Cassia, MG, Brazil. The new index appropriately expressed the importance of species in the evaluated fragment. PMID- 26676992 TI - Evidence of divergent selection for drought and cold tolerance at landscape and local scales in Abies alba Mill. in the French Mediterranean Alps. AB - Understanding local adaptation in forest trees is currently a key research and societal priority. Geographically and ecologically marginal populations provide ideal case studies, because environmental stress along with reduced gene flow can facilitate the establishment of locally adapted populations. We sampled European silver fir (Abies alba Mill.) trees in the French Mediterranean Alps, along the margin of its distribution range, from pairs of high- and low-elevation plots on four different mountains situated along a 170-km east-west transect. The analysis of 267 SNP loci from 175 candidate genes suggested a neutral pattern of east-west isolation by distance among mountain sites. F(ST) outlier tests revealed 16 SNPs that showed patterns of divergent selection. Plot climate was characterized using both in situ measurements and gridded data that revealed marked differences between and within mountains with different trends depending on the season. Association between allelic frequencies and bioclimatic variables revealed eight genes that contained candidate SNPs, of which two were also detected using F(ST) outlier methods. All SNPs were associated with winter drought, and one of them showed strong evidence of selection with respect to elevation. Q(ST)-F(ST) tests for fitness-related traits measured in a common garden suggested adaptive divergence for the date of bud flush and for growth rate. Overall, our results suggest a complex adaptive picture for A. alba in the southern French Alps where, during the east-to-west Holocene recolonization, locally advantageous genetic variants established at both the landscape and local scales. PMID- 26676993 TI - Triple helical structure of acid-soluble collagen derived from Nile tilapia skin as affected by extraction temperature. AB - BACKGROUND: Fish skin has become a new source of collagen. It is usually extracted at low temperature. Increasing the extraction temperature can increase the collagen yield. However, high temperature might cause degradation of the triple helical structure of collagen, which is related to its functional biomaterial. This work thus aimed to investigate the effect of extraction temperature on the extraction efficiency and characteristics of acid-soluble collagen (ASC), particularly its triple helical structure. RESULTS: ASC was extracted at 5 +/- 1, 15 +/- 1 and 25 +/- 1 degrees C for 0-24 h with 0.3 or 0.5 mol L(-1) acetic acid. The results showed that extraction with 0.5 mol L(-1) acetic acid gave a higher extraction efficiency than that in 0.3 mol L(-1) acetic acid (P < 0.5). Extraction at 25 +/- 1 degrees C for 5 h with 0.5 mol L(-1) acetic acid gave a higher extraction efficiency (73.73 +/- 1.28%), which is higher than that of 5 +/- 1 degrees C by about 1.7-fold. All ASC obtained were identified as type I collagen and showed similar physicochemical properties. CONCLUSION: The results showed that extraction temperature strongly affected extraction efficiency. Extraction at 25 degrees C did not affect the triple helical structure, which was confirmed by the results of Fourier transform infrared, circular dichroism spectrum and collagen self-assembly. (c) 2015 Society of Chemical Industry. PMID- 26676995 TI - Effect of Pt Nanoparticles on the Photocatalytic Activity of ZnO Nanofibers. AB - For this study, we originally realized ZnO nanofibers (~50 nm in mean radius) mixed with Pt nanoparticles (~30 nm in mean radius), prepared by pulsed laser ablation in liquid, and investigated their photocatalytic performance. The material was synthesized by the simple electrospinning method coupled with subsequent thermal treatments. Methylene blue was employed as a representative dye pollutant to evaluate the photocatalytic activity of the nanofibers. It was found that the Pt-ZnO fibers exhibit a photodegradation reaction rate that is ~40 % higher than the one obtained for reference ZnO fibers. These encouraging results demonstrate that Pt-ZnO nanofibers can be fruitfully applied for environmental applications. PMID- 26676994 TI - Impact of an Electronic Template on Documentation of Obesity in a Primary Care Clinic. AB - Identification of obesity at well-child care (WCC) examinations is a step toward intervention. Studies have shown suboptimal documentation in primary care clinics that can improve with the use of electronic health records (EHRs). This study investigated the impact of a standardized EHR template on documentation of obesity at WCC visits and its impact on physician behavior. A cohort of 585 children with severe early onset obesity (body mass index >99th percentile, age <6 years) was identified with an electronic algorithm. Complete records of visit notes were reviewed to extract history taking, counseling, and recording of obesity at a WCC visit. Use of a standardized EHR template for WCC visits is associated with improvement in rates of documentation of obesity (47% vs 34%, P < .01), without interruption of workflow. Documentation of obesity in the chart improved nutritional (66% vs 44%, P < .001) and physical activity counseling (23% vs 9%, P < .001). PMID- 26676996 TI - Investigating the Inter-Tube Conduction Mechanism in Polycarbonate Nanocomposites Prepared with Conductive Polymer-Coated Carbon Nanotubes. AB - A well-known strategy to improve the electrical conductivity of polymers is to dope them with high-aspect-ratio and conductive nanoparticles such as carbon nanotubes (CNTs). However, these nanocomposites also exhibit undesirable properties such as damage-sensitive and history-dependent conductivity because their macroscopic electrical conductivity is largely determined by the tunneling effect at the tube/tube interface. To reduce these issues, new nanocomposites have been developed with CNTs that have been coated with a conductive layer of poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate) (PEDOT/PSS). It has been posited that the insulating region between the CNTs is replaced by a conductive polymer bridge; this has not been proven up to now. We propose here to investigate in-depth how the macroscopic conductivity of these materials is changing when (1) varying the frequency of the electrical loading (impedance spectroscopy), (2) varying the mechanical hydrostatic pressure, and (3) varying the voltage of the electrical loading. The response is systematically compared to the one of conventional carbon nanotube/polycarbonate (CNT/PC) nanocomposites so we can clarify how efficiently the tunneling effect is suppressed from these composites. The objective is to elucidate further the mechanism for conduction in such material formulations. PMID- 26676997 TI - Orthogonal Thin Film Photovoltaics on Vertical Nanostructures. AB - Decoupling paths of carrier collection and illumination within photovoltaic devices is one promising approach for improving their efficiency by simultaneously increasing light absorption and carrier collection efficiency. Orthogonal photovoltaic devices are core-shell type structures consisting of thin film photovoltaic stack on vertical nanopillar scaffolds. These types of devices allow charge collection to take place in the radial direction, perpendicular to the path of light in the vertical direction. This approach addresses the inherently high recombination rate of disordered thin films, by allowing semiconductor films with minimal thicknesses to be used in photovoltaic devices, without performance degradation associated with incomplete light absorption. This work considers effects which influence the performance of orthogonal photovoltaic devices. Illumination non-uniformity as light travels across the depth of the pillars, electric field enhancement due to the nanoscale size and shape of the pillars, and series resistance due to the additional surface structure created through the use of pillars are considered. All of these effects influence the operation of orthogonal solar cells and should be considered in the design of vertically nanostructured orthogonal photovoltaics. PMID- 26676998 TI - Copper-catalyzed C-H ethoxycarbonyldifluoromethylation of imidazoheterocycles. AB - A regioselective copper-catalyzed ethoxycarbonyl-difluoromethylation of imidazo[1,2-a]pyridines has been developed through sp(2) C-H bond functionalization with BrCF2CO2Et under ambient air. A series of ethoxycarbonyldifluoromethylated imidazo[1,2-a]pyridines with broad functionalities have been synthesized. This methodology is also applicable to imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole. PMID- 26676999 TI - How Much Does Social Status Matter to Longevity?-Evidence from China's Academician Election. AB - We provide evidence for the causal impact of social status on longevity by exploiting a natural experiment in which subjects undergo a shift in their social status without considerable economic impact. We gather data on 4190 scientists who were either nominated for or successfully elected to the Chinese Academy of Science or of Engineering. Being elected as an academician in China is a boost in social status (vice-ministerial level) with negligible direct economic impact (US$30 monthly before 2009). After correcting for two sources of bias, (1) some potential academicians decease too young to be elected, leading to selection bias in favor of academicians and (2) the endogenous relationship between health and social status, we find that the enhanced social status of becoming an academician leads to approximately 1.2 years longer life. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26677000 TI - 3D Graphene-Foam-Reduced-Graphene-Oxide Hybrid Nested Hierarchical Networks for High-Performance Li-S Batteries. AB - A 3D graphene-foam-reduced-graphene-oxide hybrid nested hierarchical network is synthesized to achieve high sulfur loading and content simultaneously, which solves the "double low" issues of Li-S batteries. The obtained Li-S cathodes show a high areal capacity two times larger than that of commercial lithium-ion batteries, and a good cycling performance comparable to those at low sulfur loading. PMID- 26677001 TI - Damage to dopaminergic neurons is mediated by proliferating cell nuclear antigen through the p53 pathway under conditions of oxidative stress in a cell model of Parkinson's disease. AB - Oxidative stress is widely considered as a central event in the pathogenesis of Parkinson's disease (PD). The mechanisms underlying the oxidative damage-mediated loss of dopaminergic neurons in PD are not yet fully understood. Accumulating evidence has indicated that oxidative DNA damage plays a crucial role in programmed neuronal cell death, and is considered to be at least partly responsible for the degeneration of dopaminergic neurons in PD. This process involves a number of signaling cascades and molecular proteins. Proliferating cell nuclear antigen (PCNA) is a pleiotropic protein affecting a wide range of vital cellular processes, including chromatin remodelling, DNA repair and cell cycle control, by interacting with a number of enzymes and regulatory proteins. In the present study, the exposure of PC12 cells to 1-methyl-4-phenylpyridinium (MPP+) led to the loss of cell viability and decreased the expression levels of PCNA in a dose- and time-dependent manner, indicating that this protein may be involved in the neurotoxic actions of MPP+ in dopaminergic neuronal cells. In addition, a significant upregulation in p53 expression was also observed in this cellular model of PD. p53 is an upstream inducer of PCNA and it has been recognized as a key contributor responsible for dopaminergic neuronal cell death in mouse models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. This indicates that MPP+-induced oxidative damage is mediated by the downregulation of PCNA through the p53 pathway in a cellular model of PD. Thus, our results may provide some novel insight into the molecular mechanisms responsible for the development of PD and provide new possible therapeutic targets for the treatment of PD. PMID- 26677003 TI - Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation. AB - IMPORTANCE: Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is a rare genodermatosis in which numerous indolent, well-differentiated basal cell carcinomas develop primarily on the face and genitals, without other features characteristic of basal cell nevus syndrome. The cause is unknown. The purpose of the study was to identify a genetic basis for the syndrome and a mechanism by which the associated tumors develop. OBSERVATIONS: Whole-exome sequencing of 5 tumors and a normal buccal mucosal sample from a patient with MHIBCC was performed. A conserved splice-site mutation in 1 copy of the suppressor of fused gene (SUFU) was identified in all tumor and normal tissue samples. Additional distinct deletions of the trans SUFU allele were identified in all tumor samples, none of which were present in the normal sample. CONCLUSIONS AND RELEVANCE: A germline SUFU mutation was present in a patient with MHIBCC, and additional acquired SUFU mutations underlie the development of infundibulocystic basal cell carcinomas. The downstream location of the SUFU gene within the sonic hedgehog pathway may explain why its loss is associated with relatively well-differentiated tumors and suggests that MHIBCC will not respond to therapeutic strategies, such as smoothened inhibitors, that target upstream components of this pathway. PMID- 26677002 TI - Evaluation of free modeling targets in CASP11 and ROLL. AB - We present an assessment of 'template-free modeling' (FM) in CASP11and ROLL. Community-wide server performance suggested the use of automated scores similar to previous CASPs would provide a good system of evaluating performance, even in the absence of comprehensive manual assessment. The CASP11 FM category included several outstanding examples, including successful prediction by the Baker group of a 256-residue target (T0806-D1) that lacked sequence similarity to any existing template. The top server model prediction by Zhang's Quark, which was apparently selected and refined by several manual groups, encompassed the entire fold of target T0837-D1. Methods from the same two groups tended to dominate overall CASP11 FM and ROLL rankings. Comparison of top FM predictions with those from the previous CASP experiment revealed progress in the category, particularly reflected in high prediction accuracy for larger protein domains. FM prediction models for two cases were sufficient to provide functional insights that were otherwise not obtainable by traditional sequence analysis methods. Importantly, CASP11 abstracts revealed that alignment-based contact prediction methods brought about much of the CASP11 progress, producing both of the functionally relevant models as well as several of the other outstanding structure predictions. These methodological advances enabled de novo modeling of much larger domain structures than was previously possible and allowed prediction of functional sites. Proteins 2016; 84(Suppl 1):51-66. (c) 2015 Wiley Periodicals, Inc. PMID- 26677004 TI - Chemical doping of a core-shell silicon nanoparticles@polyaniline nanocomposite for the performance enhancement of a lithium ion battery anode. AB - New silicon based anodic materials in lithium ion batteries (Si-based LIBs) have been developed worldwide to overcome capacity decay during the lithiation/delithiation process. In this study, a composite of Si nanoparticles coated with 5-sulfoisophthalic acid (SPA) doped polyaniline (core/shell SiNPs@PANi/SPA) was prepared and applied as an anode material for LIB applications. The detailed structure of the core/shell SiNPs@PANi/SPA composite was characterized using high-resolution scanning electron microscopy before and after charging/discharging. The electrochemical measurements showed that the SiNPs@PANi/SPA anode exhibited a high capacity of 925 mA h g(-1) and high coulombic efficiency (99.6%) after long-term cycling (1000 cycles). Overall results indicated that the SPA doped polyaniline served as a conductive matrix to improve electrical contact and to provide an adhesive force in Si-based LIBs. Our approach opens a route for the design of efficient silicon nanocomposites for LIB applications. PMID- 26677005 TI - Recombinant factor VIIa concentrate versus plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors. AB - BACKGROUND: In people with haemophilia, therapeutic clotting agents might be recognised as a foreign protein and induce anti-factor VIII antibodies, known as 'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma derived, are called factor VIII 'by-passing' agents and used for treatment of bleeding in people with inhibitors. OBJECTIVES: To determine the clinical effectiveness of recombinant factor VIIa concentrate compared to plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Coagulopathies Trials Register: 23 September 2015. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials comparing recombinant factor VIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant factor VIII or factor IX concentrate; non-activated prothrombin complex concentrates; activated prothrombin complex concentrates) in people with haemophilia. Comparisons with animal-derived products were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trials (eligibility and risk of bias) and extracted data. No combined meta-analyses were performed due to the unavailability of outcomes and comparisons common to the included trials. MAIN RESULTS: A total of 15 trials were identified, two of which (with data for a total of 69 participants) were eligible for analysis. Both trials showed methodological flaws and did not show superiority of one treatment over the other. Both the treatments showed that recombinant factor VIIa and activated prothrombin complex concentrate appeared to have a similar haemostatic effect in both trials, without increasing thromboembolic risk. AUTHORS' CONCLUSIONS: Based on the separate analysis of the two available randomised trials, recombinant factor VIIa and activated prothrombin complex concentrate were found to be similar in efficacy and safety. However, there is a need for further, well-designed, adequately-powered, randomised controlled trials to assess the relative benefits and risks of using recombinant factor VIIa compared to human plasma-derived concentrates in people with haemophilia with inhibitors. It is advisable that researchers in the field define commonly agreed objective outcome measures in order to enable the pooling of their results, thus increasing the power of comparisons. To date, data could not be combined in a formal meta-analysis. For the same reason reporting concordant and discordant pairs in cross-over trials is recommended. PMID- 26677006 TI - Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model. AB - Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1beta in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing. PMID- 26677007 TI - Effect of Span 60 on the Microstructure, Crystallization Kinetics, and Mechanical Properties of Stearic Acid Oleogels: An In-Depth Analysis. AB - Modulation of crystallization of stearic acid and its derivatives is important for tuning the properties of stearate oleogels. The present study delineates the crystallization of stearic acid in stearate oleogels in the presence of Span 60. Microarchitecture analysis revealed that stearic acid crystals in the oleogels changed its shape from plate-like structure to a branched architecture in the presence of Span 60. Consequently, a significant variation in the mobility of the solute molecules inside the oleogel (Fluorescence recovery after photobleaching studies, FRAP analysis) was observed. Thermal analysis (gelation kinetics and DSC) revealed shortening of nucleation induction time and secondary crystallization with an increase in the Span 60 concentration. Furthermore, isosolid diagram suggested better physical stability of the formulations at higher proportions of Span 60. XRD analysis indicated that there was a decrease in the crystal size and the crystallinity of the stearic acid crystals with an increase in Span 60 concentration in the Span 60 containing oleogels. However, crystal growth orientation was unidirectional and found unaltered with Span 60 concentration (Avarmi analysis using DSC data). The mechanical study indicated a composition-dependent variation in the viscoelastic properties (instantaneous [tau1 ], intermediate [tau2 ], and delayed [tau3 ] relaxation times) of the formulations. In conclusion, Span 60 can be used to alter the kinetics of the crystallization, crystal habit and crystal structure of stearic acid. This study provides a number of clues that could be used further for developing oleogel based formulation. PMID- 26677009 TI - Novel cobalt quantum dot/graphene nanocomposites as highly efficient electrocatalysts for water splitting. AB - A cost-effective, non-noble metal based high-performance electrocatalyst for the oxygen evolution reaction (OER) is critical to energy conversion and storage processes. Here, we report on a facile and effective in situ strategy for the synthesis of an advanced nanocomposite material that is comprised of cobalt quantum dots (Co QDs, ~3.2 nm), uniformly dispersed on reduced graphene oxide (rGO) as a highly efficient OER electrocatalyst platform. This nanocomposite electrocatalyst afforded a mass activity of 1250 A g(-1) at a low overpotential (eta) of 0.37 V, a small Tafel slope of ~37 mV dec(-1) and a turnover frequency (TOF) of 0.188 s(-1) in 0.1 M KOH, comparing favorably with state-of-the-art RuO2, IrO2 and Pt/C catalysts. The synergy between abundant catalytically active sites through the fine dispersion of Co QDs, and enhanced electron transfer generated from the graphene resulted in first-rate electrocatalytic properties toward the OER. These merits coupled with the higher stability of the nanocomposite hold great promise for triggering breakthroughs in electrocatalysis for water splitting. PMID- 26677008 TI - Ninjurin1 regulates lipopolysaccharide-induced inflammation through direct binding. AB - Ninjurin1 is a transmembrane protein involved in macrophage migration and adhesion during inflammation. It was recently reported that repression of Ninjurin1 attenuated the lipopolysaccharide (LPS)-induced inflammatory response in macrophages; however, the precise mechanism by which Ninjurin1 modulates LPS induced inflammation remains poorly understood. In the present study, we found that the interaction between Ninjurin1 and LPS contributed to the LPS-induced inflammatory response. Notably, pull-down assays using lysates from HEK293T cells transfected with human or mouse Ninjurin1 and biotinylated LPS (LPS-biotin) showed that LPS directly bound Ninjurin1. Subsequently, LPS binding assays with various truncated forms of Ninjurin1 protein revealed that amino acids (aa) 81 100 of Ninjurin1 were required for LPS binding. In addition, knockdown experiments using Ninj1 siRNA resulted in decreased nitric oxide (NO) and tumor necrosis factor-alpha (TNFalpha) secretion upon LPS treatment in Raw264.7 cells. Collectively, our results suggest that Ninjurin1 regulates the LPS-induced inflammatory response through its direct binding to LPS, thus, identifying Ninjurin1 as a putative target for the treatment of inflammatory diseases, such as sepsis and inflammation-associated carcinogenesis. PMID- 26677010 TI - Nasal Septal Deviation and Facial Skeletal Asymmetries. AB - During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries. Using computed tomographic (CT) scans of n = 55 adult subjects, the purpose of this study was to test whether there is a correlation between septal deviation and facial asymmetries using three-dimensional (3D) geometric morphometric techniques. We calculated deviation as a percentage of septal volume relative to the volume of a modeled non-deviated septum. We then recorded skeletal landmarks representing the nasal, palatal, and lateral facial regions. Landmark data were superimposed using Procrustes analysis. First, we examined the correlation between nasal septal deviation and the overall magnitude of asymmetry. Next, we assessed whether there was a relationship between nasal septal deviation and more localized aspects of asymmetry using multivariate regression analysis. Our results indicate that while there was no correlation between septal deviation and the overall magnitude of asymmetry, septal deviation was associated with asymmetry primarily in the nasal floor and the palatal region. Septal deviation was unassociated with asymmetries in the lateral facial skeleton. Though we did not test the causal relationship between nasal septal deviation and facial asymmetry, our results suggest that the nasal septum may have an influence on patterns of adult facial form. PMID- 26677011 TI - Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels-Alder Reaction. AB - A copper(II) cofactor coupled to a testosterone anchor, copper(II)-(5-(Piperazin 1-yl)-1,10-phenanthroline)testosterone-17-hemisuccinamide (10) was synthesized and associated with a neocarzinostatin variant, NCS-3.24 (KD =3 MUm), thus generating a new artificial metalloenzyme by following a "Trojan horse" strategy. Interestingly, the artificial enzyme was able to efficiently catalyze the Diels Alder cyclization reaction of cyclopentadiene (1) with 2-azachalcone (2). In comparison with what was observed with cofactor 10 alone, the artificial enzymes favored formation of the exo products (endo/exo ratios of 84:16 and 62:38, respectively, after 12 h). Molecular modeling studies assigned the synergy between the copper complex and the testosterone (KD =13 MUm) moieties in the binding of 10 to good van der Waals complementarity. Moreover, by pushing the modeling exercise to its limits, we hypothesize on the molecular grounds that are responsible for the observed selectivity. PMID- 26677012 TI - Cryptococcus neoformans var. grubii Infection in HIV-Seronegative Patients from Northeast India: Report of Two Cases with Review of Literature. AB - Cryptococcus neoformans infection can occur in a wide range of hosts ranging from those who are severely immunosuppressed to those who are apparently immunocompetent. Two apparently immunocompetent HIV-seronegative patients with cryptococcal meningitis and multiple skin lesions, both due to C. neoformans var. grubii, are reported. Pregnancy was found as an associated factor in cryptococcal meningitis in a 20-year-old female patient from Arunachal Pradesh. Multiple skin lesions were the presenting feature of an 18-year-old male patient from Dibrugarh, eastern Assam. The organism was identified both phenotypically and by sequencing of ITS1 and ITS2 regions of rRNA gene. The cases are reported because of rarity of this infection in non-HIV-infected patients. PMID- 26677013 TI - Survivin silencing and TRAIL expression using oncolytic adenovirus increase anti tumorigenic activity in gemcitabine-resistant pancreatic cancer cells. AB - In this study, we demonstrated that survivin downregulation with TRAIL expression greatly enhanced the cytotoxic death of pancreatic cancer cells after gemcitabine treatment. Using real-time RT-PCR, we analyzed five survivin shRNAs to identify the best target sequence for suppression of human survivin, with the goal of treating gemcitabine-resistant pancreatic cancer cells. Survivin shRNA 5, corresponding to target 5, showed the greatest reduction in survivin mRNA levels. Furthermore, combined treatment with survivin shRNA-expressing adenovirus with gemcitabine plus TRAIL decreased uncleaved PARP and increased consequent PARP cleavage, which was correlated with the greatest levels of survivin downregulation and cell death. These results indicate that survivin functions as a common mediator of gemcitabine- and TRAIL-induced cell death. Using a nude mouse model implanted with MiaPaCa-2 pancreatic cancer cells, we observed tumor regression induced by an oncolytic adenovirus expressing survivin shRNA and TRAIL plus gemcitabine. Together, our findings provide a strong rationale for treating pancreatic cancer patients with both gemcitabine and oncolytic adenovirus armed with survivin shRNA and TRAIL. PMID- 26677015 TI - "Reagent-free" L-asparaginase activity assay based on CD spectroscopy and conductometry. AB - A new method to determine the catalytic parameters of L-asparaginase using circular dichroism spectroscopy (CD spectroscopy) has been developed. The assay is based on the difference in CD signal between the substrate (L-asparagine) and the product (L-aspartic acid) of enzymatic reaction. CD spectroscopy, being a direct method, enables continuous measurement, and thus differentiates from multistage and laborious approach based on Nessler's method, and overcomes limitations of conjugated enzymatic reaction methods. In this work, we show robust measurements of L-asparaginase activity in conjugates with PEG-chitosan copolymers, which otherwise would not have been possible. The main limitation associated with the CD method is that the analysis should be performed at substrate saturation conditions (V max regime). For K M measurement, the conductometry method is suggested, which can serve as a complimentary method to CD spectroscopy. The activity assay based on CD spectroscopy and conductometry was successfully implicated to examine the catalytic parameters of L-asparaginase conjugates with chitosan and its derivatives, and for optimization of the molecular architecture and composition of such conjugates for improving biocatalytic properties of the enzyme in the physiological conditions. The approach developed is potentially applicable to other enzymatic reactions where the spectroscopic properties of substrate and product do not enable direct measurement with absorption or fluorescence spectroscopy. This may include a number of amino acid or glycoside-transforming enzymes. PMID- 26677014 TI - Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation. AB - OBJECTIVE: Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as infantile convulsions and paroxysmal choreoathetosis (ICCA)-are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified as the major gene in all 3 conditions, found to be mutated in 80 to 90% of familial and 30 to 35% of sporadic cases. METHODS: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed cliniconeurophysiological workup. RESULTS: In 3 families with a total of 16 affected members, we identified the same, cosegregating heterozygous missense mutation (c.4447G>A; p.E1483K) in SCN8A, encoding a voltage-gated sodium channel. A founder effect was excluded by linkage analysis. All individuals except 1 had normal cognitive and motor milestones, neuroimaging, and interictal neurological status. Fifteen affected members presented with afebrile focal or generalized tonic-clonic seizures during the first to second year of life; 5 of them experienced single unprovoked seizures later on. One patient had seizures only at school age. All patients stayed otherwise seizure-free, most without medication. Interictal electroencephalogram (EEG) was normal in all cases but 2. Five of 16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered by stretching, motor initiation, or emotional stimuli. In 1 case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortical involvement. INTERPRETATION: Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum of combined epileptic and dyskinetic syndromes. PMID- 26677016 TI - Determination of tricyclic antidepressants in biota tissue and environmental waters by liquid chromatography-tandem mass spectrometry. AB - This work describes the optimization, validation, and application in real samples of accurate and precise analytical methods to determine tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, and clomipramine in different environmental matrices, such as water (estuary, seawater, and wastewater treatment plant effluent) and biota (fish muscle, fish liver, and mussels), which would lead to supplement the scarce information on the presence of TCAs in aquatic organisms. The analysis step performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was fully optimized to improve the sensitivity of the separation and detection steps. The extraction of solid samples was accomplished using focused ultrasonic solid-liquid extraction (FUSLE), which required a low amount of sample (0.5 g), solvent (7 mL acetonitrile/H2O, 95:5 v/v) and short extraction time (30 s). In the optimisation of the clean-up step, mixed mode solid-phase extraction (SPE) using a strong cation exchanger rendered clean extracts and the best results in terms of extraction efficiency and matrix effect. The same SPE mode was also used for the extraction and pre-concentration of TCAs from environmental water matrices. The methods afforded satisfactory apparent recovery values (86-122%) and repeatability (RSD < 5%), regardless of the matrix. Finally, the developed methods were applied to the analysis of real samples from the Biscay Coast, where TCAs were detected in both water and biota samples up to 25.9 ng/L and 1.8 ng/g, respectively. Up to our knowledge, this is the first work using FUSLE for the determination of TCAs and one of the few analyzing TCAs in biota samples. PMID- 26677017 TI - What if you could only publish 50 papers your entire career? PMID- 26677018 TI - PAL SPME Arrow--evaluation of a novel solid-phase microextraction device for freely dissolved PAHs in water. AB - After more than 25 years, solid-phase microextraction (SPME) has gained widespread acceptance as a well-automatable and flexible microextraction technique, while its instrumental basis remained mostly unchanged. The novel PAL (Prep And Load solution) SPME Arrow combines the advantages of SPME with the benefits of extraction techniques providing larger sorption phase volumes such as stir bar sorptive extraction (SBSE). It thereby avoids the inherent drawbacks of both techniques such as limitations in method automation in the case of SBSE, as well as the small sorption phase volumes and the lacking fiber robustness of classical SPME fibers. This new design is based on a robust stainless steel backbone, carrying, the screw connection to the PAL sampler, the enlarged sorption phase, and an arrow-shaped tip for conservative penetration of septa (hence the name). An outer capillary encloses this phase apart from enrichment and desorption processes and rests against the tip during transfer and penetrations, resulting in a homogeneously closed device. Here, we present an evaluation and a comparison of the novel PAL SPME Arrow with classical SPME fibers, extracting polycyclic aromatic hydrocarbons (PAHs) as model analytes, from the freely dissolved fraction in lab water and groundwater via direct immersion using polydimethylsiloxane (PDMS) as common sorption phase material. Limits of detection, repeatabilities, and extraction yields were determined for the PAL SPME Arrow and compared to data of classical SPME fibers and SBSE bars. Results indicate a significant benefit in extraction efficiency due to the larger sorption phase volume. It is accompanied by faultless mechanical robustness and thus better reliability, especially in case of prolonged, unattended, and automated operation. As an exemplary application, the water-soluble fraction of PAHs and derivatives in a roofing felt sample was quantified. PMID- 26677019 TI - Measuring internal azole and pyrethroid pesticide concentrations in Daphnia magna using QuEChERS and GC-ECD--method development with a focus on matrix effects. AB - Pyrethroids are highly toxic towards aquatic macroinvertebrates such as Daphnia magna and can be synergized when co-occurring with azole fungicides. A sensitive analytical method for the measurement of azole-pyrethroid mixtures in aquatic macroinvertebrates is not available at present. We developed and validated an extraction, cleanup, and quantification procedure for four pyrethroid insecticides and four azole fungicides at the picograms per milligram wet weight level in D. magna using a QuEChERS approach and GC-ECD analysis. Short- and long term matrix effects were analyzed by injection of a series of extracts from D. magna, and the best surrogate standards were identified through correlation analysis of analyte responses. The presence of matrix clearly stabilized the analyte responses (<=6% relative standard deviation of peak area compared to up to 22% when injected without matrix). The sensitivity was high with detection limits and limits of quantification between 58-168 and 119-571 pg mg(wet weight)( 1) for the azoles and 5.8-27 and 12-84 pg mg(wet weight)(-1) for the pyrethroids, respectively. Accuracy (% recovery) was between 95 and 111% and the precision (repeatability) below 10% relative standard deviation for all analytes. In the case of prochloraz, alpha-cypermethrin, and deltamethrin, normalization to surrogate standards led to a clear improvement of accuracy and precision by up to 8 and 4%, respectively. The method was successfully applied to the measurement of internal alpha-cypermethrin concentrations in D. magna under environmentally relevant exposure conditions (exposure to a pulse in the micrograms per liter range) with and without co-exposure to propiconazole. PMID- 26677021 TI - Development of CT-guided biopsy sampling for time-dependent postmortem redistribution investigations in blood and alternative matrices--proof of concept and application on two cases. AB - The postmortem redistribution (PMR) phenomenon complicates interpretation in forensic toxicology. Human data on time-dependent PMR are rare and only exist for blood so far. A new method for investigation of time-dependent PMR in blood as well as in alternative body fluids and tissues was developed and evaluated using automated biopsy sampling. At admission of the bodies, introducer needles were placed in liver, lung, kidney, muscle, spleen, adipose tissue, heart, femoral vein, and lumbar spine using a robotic arm guided by a computed tomography scanner (CT). Needle placement accuracy was analyzed and found to be acceptable for the study purpose. Tissue biopsies and small volume body fluid samples were collected in triplicate through the introducer needles. At autopsy (around 24 h after admission), samples from the same body regions were collected. After mastering of the technical challenges, two authentic cases were analyzed as a proof of concept. Drug concentrations of venlafaxine, O-desmethylvenlafaxine, bromazepam, flupentixol, paroxetine, and lorazepam were determined by LC-MS/MS, and the percentage concentration changes between the two time points were calculated. Concentration changes were observed with both increases and decreases depending on analyte and matrix. While venlafaxine, flupentixol, paroxetine, and lorazepam generally showed changes above 30% and more, O-desmethylvenlafaxine and bromazepam did not undergo extensive PMR. The presented study shows that CT controlled biopsy collection provides a valuable tool for systematic time dependent PMR investigation, demanding only minimal sample amount and causing minimal damage to the body. PMID- 26677020 TI - A simple nonradioactive method for the determination of the binding affinities of antibodies induced by hapten bioconjugates for drugs of abuse. AB - The accurate analytical measurement of binding affinities of polyclonal antibody in sera to heroin, 6-acetylmorphine (6-AM), and morphine has been a challenging task. A simple nonradioactive method that uses deuterium-labeled drug tracers and equilibrium dialysis (ED) combined with ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) to measure the apparent dissociation constant (K d) of antibodies to 6-AM and morphine is described. The method can readily detect antibodies with K d in the low nanomolar range. Since heroin is rapidly degraded in sera, esterase inhibitors were included in the assay, greatly reducing heroin hydrolysis. MS/MS detection directly measured the heroin in the assay after overnight ED, thereby allowing the quantitation of % bound heroin in lieu of K d as an alternative measurement to assess heroin binding to polyclonal antibody sera. This is the first report that utilizes a solution-based assay to quantify heroin-antibody binding without being confounded by the presence of 6-AM and morphine and to measure K d of polyclonal antibody to 6-AM. Hapten surrogates 6-AcMorHap, 6-PrOxyHap, MorHap, DiAmHap, and DiPrOxyHap coupled to tetanus toxoid (TT) were used to generate high affinity antibodies to heroin, 6-AM, and morphine. In comparison to competition ED-UPLC/MS/MS which gave K d values in the nanomolar range, the commonly used competition enzyme-linked immunosorbent assay (ELISA) measured the 50% inhibition concentration (IC50) values in the micromolar range. Despite the differences in K d and IC50 values, similar trends in affinities of hapten antibodies to heroin, 6-AM, and morphine were observed by both methods. Competition ED-UPLC/MS/MS revealed that among the five TT-hapten bioconjugates, TT-6-AcMorHap and TT-6-PrOxyHap induced antibodies that bound heroin, 6-AM, and morphine. In contrast, TT-MorHap induced antibodies that poorly bound heroin, while TT-DiAmHap and TT-DiPrOxyHap induced antibodies either did not bind or poorly bound to heroin, 6-AM, and morphine. This simple and nonradioactive method can be extended to other platforms, such as oxycodone, cocaine, nicotine, and methamphetamine for the selection of the lead hapten design during substance abuse vaccine development. PMID- 26677022 TI - Direct visual detection of MnO2 nanosheets within seconds. AB - The increasing application of nanomaterials will inevitably lead to their release into the environment, which may pose a threat to the environment and human health. As such, there is an urgent need to detect various nanomaterials. In the present work, we present a novel, rapid, and simple visual detection of MnO2 nanosheets in buffer solution and environmental water sample. In this assay, a redox reaction between MnO2 nanosheets and 3,3',5,5'-tetramethylbenzidine (TMB) occurred, leading to the oxidation of TMB to TMB diimine. This redox reaction generated different colors dependent on the concentration of MnO2 nanosheets, including colorless, blue, green, and yellow, which allowed semiquantitative detection of MnO2 nanosheets with the naked eye. The detection range of the visual assay was 2-15 MUg/mL, and the minimum concentration of MnO2 nanosheets can be visually detected at concentrations down to 2.0 MUg/mL. Moreover, the developed visual assay showed a high selectivity to MnO2 nanosheets over Mn(2+) ions, tetramethylammonium hydroxide, hydrogen peroxide, graphene oxide, and graphitic carbon nitride nanosheets. PMID- 26677023 TI - Comprehensive analysis of serum metabolites in gestational diabetes mellitus by UPLC/Q-TOF-MS. AB - Gestational diabetes mellitus (GDM) refers to the first sign or onset of diabetes mellitus during pregnancy rather than progestation. In recent decades, more and more research has focused on the etiology and pathogenesis of GDM in order to further understand GDM progress and recovery. Using an advanced metabolomics platform based on ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry (UPLC/Q-TOF-MS), we explored the changes in serum metabolites between women with GDM and healthy controls during and after pregnancy. Some significant differences were discovered using multivariate analysis including partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA). The dysregulated metabolites were further compared and verified in several databases to understand how these compounds might function as potential biomarkers. Analyses of the metabolic pathways associated with these potential biomarkers were subsequently explored. A total of 35 metabolites were identified, contributing to GDM progress to some extent. The identified biomarkers were involved in some important metabolic pathways including glycine, serine, and threonine metabolism; steroid hormone biosynthesis; tyrosine metabolism; glycerophospholipid metabolism; and fatty acid metabolism. The above mentioned metabolic pathways mainly participate in three major metabolic cycles in humans, including lipid metabolism, carbohydrate metabolism, and amino acid metabolism. In this pilot study, the valuable comprehensive analysis gave us further insight into the etiology and pathophysiology of GDM, which might benefit the feasibility of a rapid, accurate diagnosis and reasonable treatment as soon as possible but also prevent GDM and its related short- and long-term complications. PMID- 26677024 TI - Separation of proteins by cation-exchange sequential injection chromatography using a polymeric monolithic column. AB - Since sequential injection chromatography (SIC) emerged in 2003, it has been used for separation of small molecules in diverse samples, but separations of high molar mass compounds such as proteins have not yet been described. In the present work a poly(glycidyl methacrylate-co-ethylene dimethacrylate) (GMA-co-EDMA) monolithic column was prepared by free radical polymerization inside a 2.1-mm i.d. activated fused silica-lined stainless steel tubing and modified with iminodiacetic acid (IDA). The column was prepared from a mixture of 24% GMA, 16% EDMA, 20% cyclohexanol, and 40% 1-dodecanol (all% as w/w) containing 1% of azobisisobutyronitrile (AIBN) (in relation to monomers). Polymerization was done at 60 degrees C for 24 h. The polymer was modified with 1.0 M IDA (in 2 M Na2CO3, pH 10.5) at 80 degrees C for 16 h. Separation of myoglobin, ribonuclease A, cytochrome C, and lysozyme was achieved at pH 7.0 (20 mM KH2PO4/K2HPO4) using a salt gradient (NaCl). Myoglobin was not retained, and the other proteins were separated by a gradient of NaCl created inside the holding coil (4 m of 0.8-mm i.d. PTFE tubing) by sequential aspiration of 750 and 700 MUL of 0.2 and 0.1 M NaCl, respectively. As the flow was reversed toward the column (5 MUL s(-1)) the interdispersion of these solutions created a reproducible gradient which separated the proteins in 10 min, with the following order of retention: ribonuclease A < cytochrome C < lysozyme. The elution order was consistent with a cation-exchange mechanism as the retention increased with the isoelectric points. PMID- 26677025 TI - Optimization and comparison of miniaturized extraction techniques for PAHs from crude oil exposed Atlantic cod and haddock eggs. AB - Two miniaturized extraction methods for a wide range of 2-6 ring polycyclic aromatic hydrocarbons (PAHs) and their alkylated homologues in small lipid-rich biota samples (<=100 mg) have been developed. Both methods utilize liquid extraction (LE) prior to a clean-up step using either normal phase solid phase extraction (SPE) or mixed-phase dispersive SPE (dSPE). Optimization of the methods was achieved by comparing the type and amount of sorbents, drying agents, and solvents used. In order to improve the limits of detection (LOD) of target PAHs under high sensitivity gas chromatography-tandem mass spectrometry analysis, specific emphasis was given to minimizing lipid co-extraction. The optimized LE SPE method comprised extraction with dichloromethane/n-hexane (1:1, v/v) and clean-up by silica SPE, whereas the optimized LE-dSPE method comprised extraction with acetonitrile and clean-up with PSA and C18 sorbents. The methods were validated and directly compared through the analysis of Atlantic cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) eggs exposed to oil. The LE-SPE method resulted in lower levels of co-extracted lipids (14.1 +/- 1.7 ng/MUL) than the LE-dSPE method (60 +/- 14 ng/MUL). Achieved PAH LODs for the LE-SPE method were typically an order of magnitude lower (<5 ng/g) than for the LE-dSPE method (<125 ng/g). The LE-SPE method offers the possibility for PAH analysis of small samples of fish eggs (~100 mg) exposed to small quantities of crude oil (~1-10 MUg/L total PAHs). PMID- 26677026 TI - Naked-eye sensitive ELISA-like assay based on gold-enhanced peroxidase-like immunogold activity. AB - A naked-eye sensitive ELISA-like assay was developed based on gold-enhanced peroxidase-like activity of gold nanoparticles (AuNPs). Using human IgG (H-IgG) as an analytical model, goat anti-human IgG antibody (anti-IgG) adsorbed on microtiter plate and AuNPs-labeled anti-IgG acted as capture antibody and detection antibody, respectively. Because the surfaces of AuNPs were blocked by protein molecules, the peroxidase-like activity of AuNPs was almost inhibited, evaluated by the catalytic oxidation of peroxidase enzyme substrate 3,3',5,5' tetramethylbenzidine (TMB), which could produce a bright blue color in the presence of H2O2. Fortunately, the catalytic ability of AuNPs was dramatically increased by the deposition of gold due to the formation of a new gold shell on immunogold. Under optimal reaction conditions, the colorimetric immunoassay presented a good linear relationship in the range of 0.7-100 ng/mL and the limit of detection (LOD) of 0.3 ng/mL calculated by 3sigma/S for UV-vis detection, and obtained LOD of 5 ng/mL for naked-eye detection. The obtained results were competitive with conventional sandwich ELISA with the LOD of 1.6 ng/mL. Furthermore, this developed colorimetric immunoassay was successfully applied to diluted human serum and fetal bovine serum samples, and predicted a broad prospect for the use of peroxidase-like activity involving nanomaterials in bioassay and diagnostics. PMID- 26677027 TI - Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports. AB - The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control analysis, which can be proposed in the future as a complement to the 'urinary module' for improving steroid abuse detection capabilities. PMID- 26677028 TI - Detection of volatile organic compounds (VOCs) from exhaled breath as noninvasive methods for cancer diagnosis. AB - The detection of cancer at an early stage is often significant in the successful treatment of the disease. Tumor cells have been reported to generate unique cancer volatile organic compound (VOC) profiles which can reflect the disease conditions. The detection and analysis of VOC biomarkers from exhaled breath has been recognized as a new frontier in cancer diagnostics and health inspections owing to its potential in developing rapid, noninvasive, and inexpensive cancer screening tools. To detect specific VOCs of low concentrations from exhaled breath, and to enhance the accuracy of early diagnosis, many breath collection and analysis approaches have been developed. This paper will summarize and critically review the exhaled-breath VOC-related sampling, collection, detection, and analytical methods, especially the recent development in VOC sensors. VOC sensors are commonly inexpensive, portable, programmable, easy to use, and can obtain data in real time with high sensitivities. Therefore, many sensor-based VOC detection techniques have huge potential in clinical point-of-care use. PMID- 26677029 TI - A novel method for endothelial cell isolation. AB - The present study aimed to develop a quick and efficient method for purification of newborn endothelial cells from tumor tissues. Fresh tissues were separated from C57BL/6 mice bearing tumors derived from mouse lung cancer Lewis cells, fully minced and divided into two parts. One part was subjected to collagenase type I digestion with a vortex to form a single-cell suspension, while another part was digested but without a vortex. Then, the CD105+ cells were isolated using anti-CD105 antibody-coated Dynabeads. The isolated CD105+ cells were grown in culture medium and examined for the surface expression of CD105 by a fluorescence-activated cell sorter (FACS). The uptake of acetylated LDL and the ability to maintain capillary tube-like structure formation in the CD105+ cells were also examined by Dil-Ac-LDL uptake assay and tube formation assay. The expression of tumor newborn endothelial cells (CD105+) was tested in Lewis xenografts by immunohistochemistry. The number of cells which were obtained by the digestion process with a vortex was 5.70+/-0.23x10(4) much higher than the number without a vortex (0.32+/-0.04x10(4)) (P<0.01). The purity of CD105+ cell digestion with a vortex was significantly higher than that without a vortex. Dil Ac-LDL uptake assay and tube formation assay confirmed that the CD105+ cells digested with a vortex exhibited typical functions of endothelial cells. In conclusion, the CD105+ cells isolated by the new method had high purity and displayed features of vascular endothelial cells. The modified method provides CD105+ cells with superior conditions for mechanistic research on the development of vessel-based disease. PMID- 26677031 TI - Climate variables explain neutral and adaptive variation within salmonid metapopulations: the importance of replication in landscape genetics. AB - Understanding how environmental variation influences population genetic structure is important for conservation management because it can reveal how human stressors influence population connectivity, genetic diversity and persistence. We used riverscape genetics modelling to assess whether climatic and habitat variables were related to neutral and adaptive patterns of genetic differentiation (population-specific and pairwise FST ) within five metapopulations (79 populations, 4583 individuals) of steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, USA. Using 151 putatively neutral and 29 candidate adaptive SNP loci, we found that climate-related variables (winter precipitation, summer maximum temperature, winter highest 5% flow events and summer mean flow) best explained neutral and adaptive patterns of genetic differentiation within metapopulations, suggesting that climatic variation likely influences both demography (neutral variation) and local adaptation (adaptive variation). However, we did not observe consistent relationships between climate variables and FST across all metapopulations, underscoring the need for replication when extrapolating results from one scale to another (e.g. basin-wide to the metapopulation scale). Sensitivity analysis (leave-one-population-out) revealed consistent relationships between climate variables and FST within three metapopulations; however, these patterns were not consistent in two metapopulations likely due to small sample sizes (N = 10). These results provide correlative evidence that climatic variation has shaped the genetic structure of steelhead populations and highlight the need for replication and sensitivity analyses in land and riverscape genetics. PMID- 26677030 TI - Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma. AB - PURPOSE: We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response. METHODS: Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10 %. RESULTS: Of the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2 % of tumors had TP53 mutations. Thirty three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95 % confidence interval 2.07-20.10, P < 0.001). CONCLUSIONS: Comprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC. PMID- 26677032 TI - Conjunctival tumors in children: histopathologic diagnosis in 165 cases. AB - PURPOSE: Conjunctival tissue tumors have a varied presentation, and few series studies on pediatric patients have been published. The objective of this paper is to report the histopathologic diagnoses (spanning over 1988-2013) of conjunctival tumors in children younger than 14 years. METHODS: We conducted a retrospective, descriptive, and observational study by reviewing the database of all children in whom a conjunctival tumor was surgically removed at Hospital de Ojos y Oidos "Dr. Rodolfo Robles V.," Benemerito Comite Pro Ciegos y Sordos de Guatemala. The data pertaining to gender, age, and histopathologic diagnosis of all cases was collected. The same ocular pathologist made all diagnoses. RESULTS: One hundred sixty-five cases were found, with a mean age of 7.88 years, being 91 (55.15%) male subjects. Melanocytic lesions were the most common tumors found (30.91% of cases), with only one case (0.60%) being malignant. CONCLUSIONS: Melanocytic lesions were the most common tumors found, and of all the cases, only one was malignant; this was in a patient with xeroderma pigmentosum. These findings are consistent with those reported in other studies regarding the frequencies of the histopathology of conjunctival tumors in the pediatric population. PMID- 26677033 TI - Comparison of intravitreal ranibizumab and bevacizumab treatment for retinopathy of prematurity. AB - PURPOSE: To compare the efficacy of intravitreal ranibizumab and bevacizumab treatment for type 1 retinopathy of prematurity (ROP). METHODS: 36 eyes of 20 patients with type 1 ROP who received anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections between August 2011 and February 2013 were retrospectively evaluated. Fifteen eyes of 8 patients received 0.25 mg ranibizumab (group 1), and 21 eyes of 12 patients received 0.625 mg bevacizumab (group 2). Eyes were examined by indirect ophthalmoscopy on the first day, third day, first week, and first month and as required after injections. Laser photocoagulation was performed in cases with progression of ROP. RESULTS: The mean gestation time was 26.2 +/- 2.7 weeks in group 1 patients and 27.1 +/- 2.5 weeks in group 2 patients. No statistical difference in the time of gestation was observed between the two groups. The mean follow-up period was 20 +/- 4.5 months. Laser photocoagulation was performed in 6 of 15 eyes from group 1 and 2 of 21 eyes from group 2. No eyes developed retinal detachment during the follow-up period. CONCLUSION: Ranibizumab and bevacizumab showed an efficacy in the treatment of type 1 ROP. The incidence of disease relapse was higher in eyes which received ranibizumab. Further randomized, controlled clinical trials are required to compare the efficacy of ranibizumab and bevacizumab. PMID- 26677034 TI - Optic coherence tomography measurement of choroidal and retinal thicknesses after uncomplicated YAG laser capsulotomy. AB - PURPOSE: Optic coherence tomography (OCT) evaluation of the choroid, retina, and retinal nerve fiber layer after uncomplicated yttrium-aluminum-garnet (YAG) laser capsulotomy. METHODS: OCT analysis of retinal and choroidal structures was performed in 28 eyes of 28 patients following routine examinations before and 24 h, 72 h, 2 weeks, 4 weeks, and 12 weeks after YAG laser capsulotomy. Data were analyzed using the SPSS software. RESULTS: Data collected before YAG capsulotomy and at the above mentioned follow-up visits are summarized as follows. Mean central subfoveal choroidal thickness before YAG capsulotomy was 275.85 +/- 74.78 um; it was 278.46 +/- 83.46 um, 283.39 +/- 82.84 um, 280.00 +/- 77.16 um, 278.37 +/- 76.95 um, and 278.67 +/- 76.20 um after YAG capsulotomy, respectively. Central macular thickness was 272.14 +/- 25.76 um before YAG capsulotomy; it was 266.53 +/- 26.47 um, 269.14 +/- 27.20 um, 272.17 +/- 26.97 um, 270.91 +/- 26.79 um, and 273 +/- 26.63 um after YAG capsulotomy, respectively. Mean retinal nerve fiber layer thickness before YAG was 99.89 +/- 7.61 um; it was 98.50 +/- 8.62 um, 98.14 +/- 8.69 um, 99.60 +/- 8.39 um, 99.60 +/- 8.39 um, and 99.60 +/- 8.35 um after YAG capsulotomy, respectively. No observed change was statistically significant. No significant changes were observed with regard to mean intraocular pressure. CONCLUSIONS: After YAG laser capsulotomy, no statistically significant changes were found in choroidal, retinal, and optical nerve fiber layer thicknesses, although slight thickness changes in these structures were observed, particularly during the first days. PMID- 26677036 TI - Adjustable versus non-adjustable suture techniques for concomitant horizontal strabismus: a comparative study. AB - PURPOSE: To compare the surgical results of adjustable and non-adjustable horizontal strabismus surgery for concomitant horizontal strabismus. METHODS: The charts of 231 patients, who underwent horizontal strabismus surgery, selected using probabilistic sampling, were retrospectively reviewed. Patients were divided into two groups according to the surgical technique used and strabismus type. The adjustable suture technique was used for 107 patients (Group 1), and non-adjustable or conventional surgery was performed in the remaining 124 patients (Group 2). Patients with esotropia (ET) or exotropia (XT) of <55 prism diopters (PD) at distance were included. The following exclusion criteria were applied: all intermittent or vertical deviations, anisotropias >5 PD, syndromes, restrictive or paretic strabismus, reoperations, botulinum toxin injection, and patients postoperatively followed up for <3 months. Surgical success was set to a range between orthotropia and an esodeviation of up to 10 PD for both ET and XT. RESULTS: An amblyopia rate >50% was present in all subgroups. Significant differences between strabismus groups submitted to adjustable technique and non adjustable on postoperative day 1 were observed (p=0.00 for ET and p=0.01 for XT) and at the last visit for the XT group with a follow-up of at least 1 year (p=0.05). CONCLUSION: The adjustable suture technique produced a higher success rate than non-adjustable strabismus surgery for both ET and XT groups on postoperative day 1. For XT patients, the adjustable suture technique appears to produce better surgical results than non-adjustable surgery, when the surgical goal is long-lasting maintenance of a small hypercorrection. PMID- 26677035 TI - Characteristics of the cornea in patients with pseudoexfoliation syndrome. AB - PURPOSE: To quantify the morphological alterations in corneal nerve fibers and cells in patients with pseudoexfoliation syndrome (PEX) and their relationship with the presence of hyperreflective endothelial deposits observed using in vivo confocal microscopy. METHODS: One eye each of 37 patients with PEX and 20 age matched healthy control subjects was evaluated by in vivo corneal confocal microscopy. Patients with PEX were further classified into two groups: those with and without hyperreflective endothelial deposits. We evaluated the densities of basal epithelial cells, anterior and posterior stromal keratocytes, and endothelial cells and structure of sub-basal nerve fibers. RESULTS: The mean anterior and posterior stromal keratocyte and endothelial cell densities and corneal sub-basal nerve plexus variables were significantly lower in patients with PEX compared with those in healthy control subjects. The mean basal epithelial cell density did not significantly differ. CONCLUSION: Eyes with PEX presented decreased corneal sub-basal nerve plexus variables and cell densities in all corneas, except for the mean basal epithelial cell density. Further, a trend of lower corneal sub-basal nerve plexus measurements in patients with hyperreflective endothelial deposits compared with those without endothelial deposits was observed. PMID- 26677037 TI - Detection of Toxoplasma gondii DNA in peripheral blood and aqueous humor of patients with Toxoplasmic active focal necrotizing retinochoroiditis using real time PCR. AB - PURPOSE: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. METHODS: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of Sao Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. RESULTS: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. CONCLUSION: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease. PMID- 26677038 TI - Rebound tonometry versus Goldmann tonometry in school children: feasibility and agreement of intraocular pressure measurements. AB - PURPOSE: High intraocular pressure (IOP) is an important risk factor for a variety of pediatric ophthalmic conditions. The purpose of this study is to evaluate the feasibility, length of examination, and corneal epithelial damage induced by rebound tonometry (RBT) versus Goldmann applanation tonometry (GAT) in school children. METHODS: Healthy children (n=57) participated in a randomized, transversal study with IOP measurement by GAT followed by RBT (study arm 1) or RBT followed by GAT (study arm 2). The number of attempts to acquire a reliable IOP measurement and the length of the examination were quantified. Corneal epithelial damage induced by tonometry was evaluated. Bland-Altman analysis was performed to establish the level of agreement between the two techniques. RESULTS: The IOP was measured in all children with at least one of the devices. In both study arms, more children failed to be examined with GAT than with RBT (26% vs. 4%, and 16% vs. 6%, p<0.001, in study arm 1 and 2, respectively). The length of examination was shorter for RBT than for GAT (67.81 s +/- 35.20 s vs. 126.70 s +/- 56.60 s; p<0.0001); IOP measurements with RBT in both study arms were higher than those with GAT (15.20 +/- 2.74 mmHg vs. 13.25 +/- 2.47 mmHg, p=0.0247 and 16.76 +/- 3.99 mmHg vs. 13.92 +/- 2.08 mmHg, p=0.003, respectively). No difference was observed between RBT and GAT regarding the corneal epithelial damage caused by tonometry. CONCLUSION: IOP measurement is feasible in a greater number of children with RBT, and the examination was faster than that for GAT. Compared with GAT, RBT tended to overestimate the IOP. None of the methods induced marked corneal epithelial defects. PMID- 26677039 TI - Analysis of corneal esthesia in patients undergoing photorefractive keratectomy. AB - PURPOSE: To quantitatively analyze corneal esthesia in patients undergoing photorefractive keratectomy (PRK) surgery. METHODS: Forty-five patients selected for PRK in one eye underwent corneal esthesia using a Cochet-Bonnet esthesiometer preoperatively and 30 and 90 days postoperatively. Patients with a refractive diopter error of 4 or greater received intraoperative 0.02% mitomycin C for 20 s. RESULTS: Twenty-four (53.3%) of the 45 eyes received intraoperative 0.02% mitomycin. Decreased sensitivity was observed on postoperative day 30. By postoperative day 90, corneal esthesia had normalized but remained 14.9% lower than preoperative levels. In the mitomycin group, no recovery of corneal esthesia to normal sensitivity levels was observed. The mean esthesiometer level was 39.2 mm on postoperative day 90 (P<0.001). CONCLUSIONS: The results of the present study demonstrate recovery of corneal esthesia to normal levels at 90 days postoperatively in patients who did not receive mitomycin C. In patients administered mitomycin C, a 23.59% reduction in the corneal touch threshold was observed compared with preoperative levels indicating a failure of recovery to normal levels. PMID- 26677040 TI - Upper lid crease approach for margin rotation in trachomatous cicatricial entropion without external sutures. AB - PURPOSE: To describe the use of a lid crease incision for upper eyelid margin rotation in cicatricial entropion combining internal traction on the anterior lamella, tarsotomy, and tarsal overlap without external sutures. METHODS: Surgical description: The main steps of the procedure consisted of exposure of the entire tarsal plate up to the eyelashes followed by tarsotomy through the conjunctiva. A double-armed 6.0 polyglactin suture was then passed through the distal tarsal fragment to the marginal section of the orbicularis oculi muscle. As the sutures were tied, the distal tarsus advanced over the marginal section, and traction was exerted on the marginal strip of the orbicularis muscle. There were no bolsters or external knots. The pretarsal skin-muscle flap was closed with a 6.0 plain gut suture. RESULTS: We used this procedure at a tertiary hospital in Saudi Arabia from 2013 to 2014. Sixty upper lids of 40 patients (23 women and 17 men) were operated on, with an age range of 44-99 years [mean +/- standard deviation (SD) = 70.9 +/- 13.01 years]. Bilateral surgery was performed on 21 patients. Follow-up ranged from 1 to 12 months (mean 3.0 +/- 2.71 months). Forty percent of the patients (24 lids) had more than 3 months' follow-up. The postoperative lid margin position was good in all cases. Trichiasis (two lashes) was observed in only one patient with unilateral entropion on the medial aspect of the operated lid. CONCLUSIONS: The upper lid margin can be effectively rotated through a lid crease incision with internal sutures. The technique combines the main mechanisms of the Wies and Trabut approaches and avoids the use of bolsters or external sutures, which require a second consultation to be removed. Some other lid problems, such as ptosis, retraction, or dermatochalasis, can be concomitantly addressed during the procedure. PMID- 26677041 TI - Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis. AB - PURPOSE: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), prostaglandin E2 (PGE2), and myeloperoxidase (MPO) in rabbits with endotoxin-induced experimental uveitis. METHODS: Twenty four New Zealand white rabbits were divided into four groups (n=6 each): control (CG), morphine (MG), naloxone (NG), and morphine-naloxone (MNG) groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 ug of lipopolysaccharide (LPS) endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge) and laser flaremetry were performed before (baseline), and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-alpha, IL-1 beta, PGE2, and MPO. RESULTS: No significant differences in clinical parameters and flare values were observed between the study groups. TNF alpha and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P<0.05). Significant differences in PGE2 levels were observed between the MG and NMG groups (P<0.05). A trend toward increased MPO activity was observed in response to uveitis induction; however, this trend did not reach statistical significance (P>0.05). CONCLUSIONS: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS. PMID- 26677042 TI - Bilateral isolated lens coloboma associated with bicuspid aortic valve. AB - A 27-year-old woman presented with a history of long-standing poor vision in both eyes. Ophthalmologic examination after pupillary dilatation revealed bilateral lens coloboma situated in the inferotemporal quadrant. No associated ocular abnormalities were seen, except amblyopia. A bicuspid aortic valve was observed during echocardiography during systemic evaluation. Lens coloboma usually occurs unilaterally; however, bilateral lens coloboma which is isolated or associated with other ocular malformations is also encountered. This is the first description of bilateral isolated lenticular coloboma associated with bicuspid aortic valve. Although the association between bicuspid aortic valve and lens coloboma may be an incidental finding, they may be components of an unknown syndrome. PMID- 26677043 TI - Molten metal-related ocular thermal burn: report on two cases. AB - We report two cases of severe thermal burns on the ocular surface and its adnexal appendages that developed secondary to exposure to molten heavy metal with a melting temperature of near-thousand degree Celsius. Despite aggressive intervention and strict monitoring, the profound inflammation caused significant damage to the ocular surface, ending up in an intractable infection with an unfavorable outcome. The heat of the molten metal at impact, the heat-retaining capacity of the heavy metal, the total area of the ocular surface exposed to the molten metal, and the duration of exposure determined the severity of the injury. The unfavorable outcome, despite an intensive treatment, in terms of visual acuity and cosmetic appearance, should be explicitly explained to the patient, and a psychiatrist consultation should be considered if necessary. PMID- 26677044 TI - Acute lymphoblastic leukemia presenting with bilateral serous macular detachment. AB - Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10) developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+) was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations. PMID- 26677045 TI - Pachychoroid neovasculopathy in a male patient: a case report. AB - Pachychoroid neovasculopathy is a form of type 1 (subretinal pigment epithelium) neovascularization characterized by the involvement of dilated choroidal vessels in areas of increased choroidal thickness. This disease was originally described in three white female patients. Here we report the multimodal evaluation of a clinical case of PN in a white male patient. PMID- 26677046 TI - Rho kinase inhibitors for glaucoma treatment - Review. AB - Glaucoma is a progressive optic neuropathy characterized by the loss of ganglion cells and their axons. A major risk factor for glaucomatous visual field loss is elevated intraocular pressure (IOP), and several studies have shown that lowering IOP reduces the risk of glaucomatous progression. Currently, an increasing number of researches involve Rho kinase inhibitors, which are a new pharmacological class of hypotensive agents specifically targeting the diseased trabecular outflow pathway. Rho kinase inhibitors reduce IOP by increasing aqueous humor drainage through the primary outflow pathway in the eye, which is known as the trabecular meshwork. In addition to improving the outflow facility of the trabecular meshwork, Rho kinase inhibitors also enhance retinal ganglion cell survival after ischemic injury and increase ocular blood flow. PMID- 26677047 TI - A review of "cataract surgery teaching". PMID- 26677048 TI - Production of an intraocular device using 3D printing: an innovative technology for ophthalmology. PMID- 26677049 TI - Could you imagine that much of images? PMID- 26677050 TI - To prosecute or not to prosecute: Law students' judicial decisions in CSA cases. AB - Child sexual abuse (CSA) investigations are complicated and few cases are prosecuted. The aim of the present study was to investigate judicial decisions in CSA investigations. Seventy-one law students (42 females, 29 males) read a vignette depicting a CSA investigation, assessed the complainant's and the accused's credibility, and if the case should be prosecuted or not. The participants were assigned to one of four conditions defined by a 2 (evidence: high probative value vs. low probative value) * 2 (complainant demeanour: emotional vs. neutral) factorial design. Females assigned higher credibility to the complainant than did males and males assigned higher credibility to the accused than did females. Emotionality, but not evidential value, affected credibility judgements: Females believed less in the suspect when the child behaved in an emotional manner. Most participants (94.4%) thought that the case should be prosecuted, though only 73.2% believed that prosecution could be corroborated. Corroboration of prosecution was affected by evidential value, but not emotionality. The results indicate that the behavior of alleged crime victims might affect males and females differently, which in turn could lead to biased judicial decisions in CSA investigations. PMID- 26677051 TI - Human Antigen R Binding and Regulation of SOX2 mRNA in Human Mesenchymal Stem Cells. AB - Since 2005, sex determining region y-box 2 (SOX2) has drawn the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in regenerative medicine. Mitoxantrone is a drug that acts on nucleic acids primarily used to treat certain types of cancer and was recently shown to ameliorate the outcome of autoimmune diseases such as multiple sclerosis. In addition, mitoxantrone has been shown to inhibit the binding of human antigen R (HuR) RNA-binding protein to tumor necrosis factor-alpha mRNA. Our results show that HuR binds to the 3' untranslated region of SOX2 mRNA together with the RNA-induced silencing complex miR145. The HuR binding works by stabilizing the interaction between the 3' untranslated region and the RNA-induced silencing complex. Cell exposure to mitoxantrone leads to HuR detachment and the subsequent prolongation of the SOX2 mRNA half-life. The prolonged SOX2 half-life allows improvement of the spheroid forming capability of the adipose-derived stem cells. The silencing of HuR confirmed the above observations and illustrates how the RNA-binding protein HuR may be a required molecule for regulation of SOX2 mRNA decay. PMID- 26677052 TI - DABCO-catalyzed unusual [4 + 2] cycloaddition reaction: non-substituted allenoate acts as a four-carbon synthon and facile synthesis of spirooxindoles. AB - A DABCO-catalyzed domino reaction between methyleneoxindoles and allenoates which enables the direct synthesis of spirooxindoles is reported. This is the first example of a non-substituted allenoate to act as a four-carbon synthon in a tertiary amine-catalyzed reaction. PMID- 26677053 TI - Relationships between neurocognitive functioning, mood, and quality of life in patients with temporal lobe glioma. AB - OBJECTIVE: While neurocognitive functioning (NCF) and mood disturbance share a relationship with health-related quality of life (HRQOL), few studies have examined relationships between these constructs in glioma patients prior to treatment. METHODS: Newly diagnosed patients with glioma in the left (N = 73; 49% glioblastoma) or right (N = 30; 57% glioblastoma) temporal lobe completed neuropsychological testing and self-report measures of HRQOL (Functional Assessment of Cancer Therapy (FACT)-General and Brain module) and mood (Beck Depression Inventory-Second Edition and State-Trait Anxiety Inventory). RESULTS: Verbal learning and memory, executive function, and language abilities were associated with various HRQOL scales. Stepwise linear regression showed that verbal learning predicted scores on the general well-being scale and brain module, processing speed predicted social well-being scores, and executive functioning predicted functional well-being scores on the FACT. Upper extremity strength also predicted scores on the functional well-being subscale and brain module. Mood was more strongly associated with HRQOL domains than NCF, with depressive symptoms accounting for a large proportion of variance across most subscales. CONCLUSIONS: In patients with temporal lobe glioma, depressive symptoms are strongly related to most aspects of HRQOL but not with NCF. NCF, specifically verbal learning and memory, executive functioning, and processing speed, also show direct relationships with numerous aspects of HRQOL. These findings underscore the importance of multimodal assessment of NCF and mood in this population. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26677054 TI - Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-kappaB in vitro but have a low impact on hepatocellular cells. AB - Increases in pro-inflammatory cytokine levels and tissue-infiltrating leukocytes have been closely linked to increased systemic and local inflammation, which result in organ injury. Previously, we demonstrated the beneficial and hepatoprotective anti-inflammatory effects of acute ethanol (EtOH) ingestion in an in vivo model of acute inflammation. Due to its undesirable side-effects, however, EtOH does not represent a therapeutic option for treatment of acute inflammation. Therefore, in this study, we compared the effects of acute EtOH exposure with ethyl pyruvate (EtP) as an alternative anti-inflammatory drug in an in vitro model of hepatic and pulmonary inflammation. Human hepatocellular carcinoma cells Huh7 and alveolar epithelial cells A549 were stimulated with either interleukin (IL) IL-1beta (1 ng/ml, 24 h) or tumor necrosis factor (TNF) (10 ng/ml, 4 h), and then treated with EtP (2.5-10 mM), sodium pyruvate (NaP, 10 mM) or EtOH (85-170 mM) for 1 h. IL-6 or IL-8 release from Huh7 or A549 cells, respectively, was measured by an enzyme-linked immunosorbent assay. Neutrophil adhesion to cell monolayers and CD54 expression were also analyzed. Bcl-2 and Bax gene expression was determined by RT-qPCR, and western blot analysis was performed to determine the mechanisms involved. Treating A549 cells with either EtOH or EtP significantly reduced the IL-1beta- or TNF-induced IL-8 release, whereas treating Huh7 cells did not significantly alter IL-6 release. Similarly, neutrophil adhesion to stimulated A549 cells was significantly reduced by EtOH or EtP, whereas for Huh7 cells the tendency for reduced neutrophil adhesion rates by EtOH or EtP was not significant. CD54 expression was noticeably reduced in A549 cells, but this was not the case in Huh7 cells after treatment. The Bax/Bcl-2 ratio was dose-dependently decreased by EtOH and by high-dose EtP in A549 cells, indicating a reduction in apoptosis, whereas this effect was not observed in Huh7 cells. The underlying mechanisms involve reduced phosphorylation of Akt and nuclear factor-kappaB (NF-kappaB) p65. We noted that as with EtP, EtOH reduced the inflammatory response in lung epithelial cells under acute inflammatory conditions. However, due to the low impact which EtP and EtOH had on the hepatocellular cells, our data suggest that both substances exerted different effects depending on the cellular entity. The possible underlying mechanisms involved the downregulation of Akt and the transcription factor NF-kappaB, but further research on this subject is required. PMID- 26677055 TI - A Chiroptical Logic Circuit Based on Self-Assembled Soft Materials Containing Amphiphilic Spiropyran. AB - A chiral logic circuit is proposed based on the multiple chiroptical responsiveness of a supramolecular gel material. The gel is fabricated by mixing a chiral gelator and a spiropyran derivative. Chiral responsiveness including the chiral switch and the logic gate is realized through the combined chirality transfer, photochromism, and acidichromism of the system. PMID- 26677056 TI - Improved de novo structure prediction in CASP11 by incorporating coevolution information into Rosetta. AB - We describe CASP11 de novo blind structure predictions made using the Rosetta structure prediction methodology with both automatic and human assisted protocols. Model accuracy was generally improved using coevolution derived residue-residue contact information as restraints during Rosetta conformational sampling and refinement, particularly when the number of sequences in the family was more than three times the length of the protein. The highlight was the human assisted prediction of T0806, a large and topologically complex target with no homologs of known structure, which had unprecedented accuracy-<3.0 A root-mean square deviation (RMSD) from the crystal structure over 223 residues. For this target, we increased the amount of conformational sampling over our fully automated method by employing an iterative hybridization protocol. Our results clearly demonstrate, in a blind prediction scenario, that coevolution derived contacts can considerably increase the accuracy of template-free structure modeling. Proteins 2016; 84(Suppl 1):67-75. (c) 2015 Wiley Periodicals, Inc. PMID- 26677057 TI - Equivalent Increases in Circulating GLP-1 Following Jejunal Delivery of Intact and Hydrolysed Casein: Relevance to Satiety Induction Following Bariatric Surgery. AB - BACKGROUND: Both Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) decrease the latency of food delivery to the proximal small intestine. This is implicated in exaggerated post-prandial release of glucagon-like peptide 1 (GLP-1), which provokes early satiety and reductions in food intake. Altered stomach anatomy also creates a deficit in enzymatic pre-processing. The impact of this state effect as a modulator of gut hormone responses remains underexplored. METHODS: A double-blind cross-over trial study was conducted in 13 healthy subjects assigned to receive in the fasted state and in random order at 1 week apart, a direct jejunal infusion of either intact casein or a casein hydrolysate. Downstream effects on GLP-1 release, ratings of hunger and fullness and food and water intake on each study day were recorded when an ad libitum meal was provided 30 min after the infusion. RESULTS: Circulating GLP-1 was increased 25 min after infusions and peaked to a similar degree at 15 min post-meal initiation. The hormone surge had no impact on ratings of hunger and fullness ahead of the ad libitum meal. The kinetic and magnitude of satiation following each infusion was not significantly different. Food and water intake were likewise not differentially impacted by the two infusion types. CONCLUSIONS: Protein macronutrient state upon arrival in the small intestine does not in isolation impact upon GLP-1 responses and subsequent onset of satiety. This potentially points to rate of delivery being the dominant factor in exaggerated post-prandial GLP-1 responses in patients post-RYGB and VSG. PMID- 26677058 TI - Clinical and Economic Evaluation of Absorbable Staple Line Buttressing in Sleeve Gastrectomy in High-Risk Patients. AB - BACKGROUND: Gastric leaks and bleeding are the most important complications after laparoscopic sleeve gastrectomy (LSG). The use of absorbable membranes as staple line reinforcement may decrease this risk. On the other hand, these materials bring additional costs and their economic impact is not well known. The purpose of this study was to assess the clinical and economic performance of one of the commercially available buttressing absorbable materials when treating a high-risk population. METHODS: A retrospective, observational, and comparative study was conducted at Montpellier University Hospital, France, between July 2013 and September 2014. Patients undergoing LSG, who were at a high risk for leaks and bleeding, were included and treated according to two groups: no buttressing (July 2013 to January 2014) and buttressing (February 2014 to September 2014). Clinical and economic outcomes were measured throughout the first 6 months. RESULTS: Two hundred two patients were included in the study: 116 during the no stapling reinforcement period and 86 during the buttressing period. Baseline characteristics were similar. There was no significant difference between the two groups regarding gastric leaks. However, buttressing reduced hemorrhagic complications (0 vs 8.6 %, p = 0.005) and decreased average total hospital costs for the first hospitalization (5768 vs 6025 ?, p < 0.001), as well as 6-month total inpatient cost (5944 vs. 6246 ?, p < 0.001). CONCLUSIONS: Staple line reinforcement with absorbable material reduces bleeding in high-risk population. Therefore, this type of material can also result in cost-savings. PMID- 26677059 TI - Impact of Pregnancy on Weight Loss and Quality of Life Following Gastric Banding. AB - BACKGROUND-OBJECTIVES: Despite pregnancy being a common event following laparoscopic adjustable gastric banding (LAGB), there is little comprehensive data regarding its effect on postoperative outcome. The aim of this study was to assess the impact of pregnancy on the postoperative changes in quality of life (QOL) and total weight loss 3 years after LAGB. SETTING: Multi-institutional, France. METHODS: This is a study of the subgroup of 561 women of childbearing age included in a 3-year prospective multicenter trial assessing the results of patients undergoing LAGB surgery. Data from the 61 women who got pregnant and delivered during the follow-up period were compared with the 270 who did not. RESULTS: Pregnant women achieved lower final weight loss compared to the non pregnant group [final body mass index (BMI) 35.4 vs. 31.1 kg/m(2), p < 0.0001; excess weight loss (%EBL) 43.6 vs. 64.7 %, p < 0.0001]. Longitudinal assessment demonstrated pregnancy as a significant and independent factor of poor weight loss (p < 0.0001). The timing of conception after LAGB (between the first 18 months or after) had no significant impact on weight loss changes. There was no significant difference in short form-36 health survey (SF-36) QOL scores between both groups. CONCLUSIONS: Pregnancy following gastric banding affects negatively postoperative final weight loss, even if occurring 18 months postoperatively, but has no effect on QOL improvement. PMID- 26677060 TI - Genomic Rearrangements in Unusual and Atypical Melanocytic Neoplasms. PMID- 26677062 TI - Preference Mapping of Soymilk with Different U.S. Consumers. AB - This study determined and compared drivers of liking for unflavored soymilk with different U.S. consumer groups. A highly trained panel documented appearance, mouthfeel and flavor attributes of 26 commercial soymilks. Twelve representative soymilks were then selected for evaluation by consumers from 3 age/cultural categories (n = 75 each category; Caucasian/African American females aged 18 to 30 y; Asian females aged 18 to 30 y; Caucasian/African American females aged 40 to 64 y). Consumers evaluated overall liking and liking and intensity of specific attributes. Results were evaluated by analysis of variance, followed by internal and external preference mapping. Age had no effect on overall liking, while ethnicity did (Caucasian/African American compared with Asian; P < 0.05). Caucasians/African Americans differentiated soymilks more than Asians and assigned a wider range of liking scores than Asians (2.1 to 7.2 compared with 4.0 to 6.1). Three consumer clusters were identified. Sweet taste with vanilla/vanillin and sweet aromatic flavors and higher viscosity were preferred by most consumers and differences between consumer clusters were primarily in drivers of dislike. Drivers of dislike were not identified for Cluster 1 consumers while Clusters 2 and 3 consumers (n = 84, n = 80) disliked beany, green/grassy and meaty/brothy flavors and astringency. Cluster 3 (n = 80) consumers scored all soymilks higher in liking (P < 0.05) than Cluster 2 consumers, and were willing to overlook disliked attributes with the addition of sweet taste, whereas the Cluster 2 consumers were not. These findings can be utilized to produce soymilks with attributes that are well liked by target consumers and to tailor attributes for segments of the population that have not yet been accommodated. PMID- 26677061 TI - Potential drawbacks in cell-assisted lipotransfer: A systematic review of existing reports (Review). AB - Cell-assisted lipotransfer (CAL) has been widely used in various clinical applications, including breast augmentation following mammectomy, soft-tissue reconstruction and wound healing. However, the clinical application of CAL has been restricted due to the transplanted fat tissues being readily liquefied and absorbed. The present review examines 57 previously published studies involving CAL, including fat grafting or fat transfer with human adipose-stem cells in all known databases. Of these 57 articles, seven reported the clinical application of CAL. In the 57 studies, the majority of the fat tissues were obtained from the abdomen via liposuction of the seven clinical studies, four were performed in patients requiring breast augmentation, one in a patient requiring facial augmentation, one in a patient requiring soft tissue augmentation/reconstruction and one in a patient requiring fat in their upper arms. Despite the potential risks, there has been an increased demand for CAL in in cosmetic or aesthetic applications. Thus, criteria and guidelines are necessary for the clinical application of CAL technology. PMID- 26677063 TI - Determination of mosaicity in oriented stacks of lipid bilayers. AB - Two methods of measuring the misorientation of domains in oriented multilamellar stacks of lipid bilayers superficially appeared to give different values for the mosaic spread. It is first shown that the traditional rocking method and a newer ring method give the same value of the mosaic spread when the two types of data are similarly analyzed. Both indicate a long-tailed, nearly Lorentzian, mosaic distribution function. Our primary innovation is the analysis of ring data as a function of the rocking angle. For our best oriented DOPC sample, this analysis is consistent with a single Lorentzian mosaic distribution function with width 0.05 degrees . In contrast, samples of DMPC indicate a more complex mosaic distribution and larger widths. PMID- 26677064 TI - MicroRNA-126 inhibits proliferation and metastasis by targeting pik3r2 in prostate cancer. AB - The dysregulation of miR-126 has been reported to correlate with the progression of several cancer types. The present study demonstrated that miR-126 was significantly downregulated in prostate cancer (PCa) tissues compared with normal prostate tissues. In vitro and in vivo studies indicated that forced overexpression of miR-126 significantly suppressed the proliferation of PCa cell lines. Additionally, a Transwell assay showed that enhanced expression of miR-126 inhibited metastasis in PCa in vitro. Furthermore, pik3r2 was confirmed to be a direct target of miR-126 in PCa. It was also shown that pik3r2 was upregulated in PCa tissues and this inversely correlated with miR-126 in PCa tissues. In conclusion, these results revealed that aberrant expression of miR-126 promoted the progression of PCa and may serve as a novel therapeutic biomarker for PCa. PMID- 26677065 TI - Association of interferon lambda-1 with herpes simplex viruses-1 and -2, Epstein Barr virus, and human cytomegalovirus in chronic periodontitis. AB - AIM: Periodontal tissues facilitate the homing of herpes viruses that elicit the immune-inflammatory response releasing the interferons (IFN). IFN lambda-1 (lambda1) can suppress the replication of viruses, and induces the antiviral mechanism. The aim of the present study was to evaluate the association between IFN-lambda1 and periodontal herpes viruses in the immunoregulation of chronic periodontal disease. METHODS: The cross-sectional study design included 30 chronic periodontitis patients with a mean age of 42.30 +/- 8.63 years. Gingival crevicular fluid collected was assessed for IFN-lambda1 using enzyme-linked immunosorbent assay and four herpes viruses were detected using multiplex polymerase chain reaction technique. IFN-lambda1 levels were compared between virus-positive and -negative patients for individual and total viruses. RESULTS: Fifty per cent (n = 15) of patients were positive for the four herpes viruses together; 50% (n = 15), 30% (n = 9), 26.7% (n = 8), and 40% (n = 12) were positive for herpes simplex virus (HSV)-1, Epstein-Barr virus, HSV-2, and human cytomegalovirus, respectively. The mean concentrations of IFN-lambda1 in virus positive patients (14.38 +/- 13.95) were lower than those of virus-negative patients (228.26 +/- 215.35). INF-lambda1 levels in individual virus groups were also lower in virus-positive patients compared to virus-negative patients, with P < 0.001. CONCLUSIONS: These results suggest that IFN-lambda1 could have antiviral and therapeutic value against the viruses in the pathogenesis of chronic periodontitis. PMID- 26677066 TI - Rapid synthesis of hybrids and hollow PdO nanostructures by controlled in situ dissolution of a ZnO nanorod template: insights into the formation mechanism and thermal stability. AB - Hollow nanomaterials have attracted a lot of interest by virtue of their wide range of applications that arise primarily due to their unique architecture. A common strategy to synthesize hollow nanomaterials is by nucleation of the shell material over a preformed core and subsequent dissolution of the core in the second step. Herein an ultrafast, microwave route has been demonstrated, to synthesize PdO nanotubes in a single step using ZnO as a sacrificial template. The mechanism of the nanotube formation has been investigated in detail using control experiments. By tuning the starting ratio of PdCl2 : ZnO, hollow to hybrid PdO nanostructures could be obtained using the same method. Conversion of the PdO to Pd nanotubes has been shown by simple NaBH4 treatment. The thermal stability of the PdO nanotubes has been studied. The insights presented here are general and applicable for the synthesis of hybrids/hollow structures in other systems as well. PMID- 26677067 TI - Peptides Targeting EGF Block the EGF-EGFR Interaction. AB - Epidermal growth factor receptor (EGFR) is a key target in chemotherapy. Some drugs acting on the receptor are currently in use; however, drug resistance, which causes tumour relapse, calls for the discovery of alternative inhibitors. Using docking and receptor hotspot mimicry, we have designed novel peptides directed at EGF, the main growth factor ligand of EGFR. An array of biophysical techniques was used to characterise the structure and interaction of these ligands with the target protein. Both design methods identified peptides able to bind EGF, and the capacity of these peptides to inhibit the interaction between EGF and EGFR was demonstrated in two in vitro systems. Based on targeting the smaller companion of a protein-protein interaction, the new approach described herein can be envisaged as a parallel drug design strategy, and our compounds represent the first in a new class of binders that could serve as complementary compounds in potential multidrug cancer therapy. PMID- 26677068 TI - Quantitative Raman spectral changes of the differentiation of mesenchymal stem cells into islet-like cells by biochemical component analysis and multiple peak fitting. AB - Mesenchymal stem cells (MSCs) differentiate into islet-like cells, providing a possible solution for type I diabetes treatment. To search for the precise molecular mechanism of the directional differentiation of MSC-derived islet-like cells, biomolecular composition, and structural conformation information during MSC differentiation, is required. Because islet-like cells lack specific surface markers, the commonly employed immunostaining technique is not suitable for their identification, physical separation, and enrichment. Combining Raman spectroscopic data, a fitting accuracy-improved biochemical component analysis, and multiple peaks fitting approach, we identified the quantitative biochemical and intensity change of Raman peaks that show the differentiation of MSCs into islet-like cells. Along with increases in protein and glycogen content, and decreases in deoxyribonucleic acid and ribonucleic acid content, in islet-like cells relative to MSCs, it was found that a characteristic peak of insulin (665 cm-1) has twice the intensity in islet-like cells relative to MSCs, indicating differentiation of MSCs into islet-like cells was successful. Importantly, these Raman signatures provide useful information on the structural and pathological states during MSC differentiation and help to develop noninvasive and label-free Raman sorting methods for stem cells and their lineages. PMID- 26677069 TI - Vibrational mapping of sinonasal lesions by Fourier transform infrared imaging spectroscopy. AB - Fourier transform infrared imaging (FTIRI) is a powerful tool for analyzing biochemical changes in tumoral tissues. The head and neck region is characterized by a great variety of lesions, with different degrees of malignancy, which are often difficult to diagnose. Schneiderian papillomas are sinonasal benign neoplasms arising from the Schneiderian mucosa; they can evolve into malignant tumoral lesions (squamous cell carcinoma). In addition, they can sometimes be confused with the more common inflammatory polyps. Therefore, an early and definitive diagnosis of this pathology is mandatory. Progressing in our research on the study of oral cavity lesions, 15 sections consisting of inflammatory sinonasal polyps, benign Schneiderian papillomas, and sinonasal undifferentiated carcinomas were analyzed using FTIRI. To allow a rigorous description of these pathologies and to gain objective diagnosis, the epithelial layer and the adjacent connective tissue of each section were separately investigated by following a multivariate analysis approach. According to the nature of the lesion, interesting modifications were detected in the average spectra of the different tissue components, above all in the lipid and protein patterns. Specific band-area ratios acting as spectral markers of the different pathologies were also highlighted. PMID- 26677070 TI - In vivo wide-field multispectral scanning laser ophthalmoscopy-optical coherence tomography mouse retinal imager: longitudinal imaging of ganglion cells, microglia, and Muller glia, and mapping of the mouse retinal and choroidal vasculature. AB - Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) provide complementary views of the retina, with the former collecting fluorescence data with good lateral but relatively low-axial resolution, and the latter collecting label-free backscattering data with comparable lateral but much higher axial resolution. To take maximal advantage of the information of both modalities in mouse retinal imaging, we have constructed a compact, four-channel, wide-field (~50 deg) system that simultaneously acquires and automatically coregisters three channels of confocal SLO and Fourier domain OCT data. The scanner control system allows "zoomed" imaging of a region of interest identified in a wide-field image, providing efficient digital sampling and localization of cellular resolution features in longitudinal imaging of individual mice. The SLO is equipped with a "flip-in" spectrometer that enables spectral "fingerprinting" of fluorochromes. Segmentation of retina layers and en face display facilitate spatial comparison of OCT data with SLO fluorescence patterns. We demonstrate that the system can be used to image an individual retinal ganglion cell over many months, to simultaneously image microglia and Muller glia expressing different fluorochromes, to characterize the distinctive spatial distributions and clearance times of circulating fluorochromes with different molecular sizes, and to produce unequivocal images of the heretofore uncharacterized mouse choroidal vasculature. PMID- 26677071 TI - Tri-band spectroscopic optical coherence tomography based on optical parametric amplification for lipid and vessel visualization. AB - A tri-band spectroscopic optical coherence tomography (SOCT) system has been implemented for visualization of lipid and blood vessel distribution. The tri band swept source, which covers output spectrum in 1.3, 1.5, and 1.6 MUm wavelength windows, is based on a dual-band Fourier domain mode-locked laser and a fiber optical parametric amplifier. This tri-band SOCT can further differentiate materials, e.g., lipid and artery, qualitatively by contrasting attenuation coefficients difference within any two of these bands. Furthermore, ex vivo imaging of both porcine artery with artificial lipid plaque phantom and mice with coronary artery disease were demonstrated to showcase the capability of our SOCT. PMID- 26677072 TI - Errata: Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis. PMID- 26677073 TI - Arsenite-induced endoplasmic reticulum-dependent apoptosis through disturbance of calcium homeostasis in HBE cell line. AB - Calcium (Ca2+ ) is a ubiquitous cell signal responsible for multiple fundamental cellular functions, including apoptosis. Whether the homeostasis of Ca2+ is involved in arsenite-induced apoptosis remains unclear. In this study, we observed that arsenite significantly elevated the intracellular Ca2+ concentration in a dose- and time-dependent manner. By using the Ca2+ -ATPase inhibitor, thapsigargin, and the inositol 1,4,5- trisphosphate receptors (IP3Rs) inhibitor, heparin, we further confirmed that the disturbance of endoplasmic reticulum (ER) Ca2+ homeostasis caused Ca2+ overload in the cells. Moreover, loss of ER Ca2+ homeostasis also led to ER stress, mitochondrial dysfunction, and NF kappaB activation. Importantly, pretreatment of cells with heparin remarkably attenuated the elevated cell apoptosis induced by arsenite, but inhibition of ER Ca2+ uptake with thapsigargin exacerbated arsenite-induced cell damage significantly. Together, we demonstrated for the first time that arsenite disturbed the Ca2+ homeostasis in ER, which subsequently led to ER stress, mitochondrial dysfunction, and NF-kappaB nuclear translocation, and thus consequently triggering cell apoptosis. Our findings indicate regulation of disrupted Ca2+ homeostasis in ER may be a potential strategy for prevention of arsenite toxicity. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 197-216, 2017. PMID- 26677074 TI - Rare variants in MC1R/TUBB3 exon 1 are not associated with Parkinson's disease. PMID- 26677075 TI - Cognition Enhancing and Neuromodulatory Propensity of Bacopa monniera Extract Against Scopolamine Induced Cognitive Impairments in Rat Hippocampus. AB - Cognition-enhancing activity of Bacopa monniera extract (BME) was evaluated against scopolamine-induced amnesic rats by novel object recognition test (NOR), elevated plus maze (EPM) and Morris water maze (MWM) tests. Scopolamine (2 mg/kg body wt, i.p.) was used to induce amnesia in rats. Piracetam (200 mg/kg body wt, i.p.) was used as positive control. BME at three different dosages (i.e., 10, 20 and 40 mg/kg body wt.) improved the impairment induced by scopolamine by increasing the discrimination index of NOR and by decreasing the transfer latency of EPM and escape latency of MWM tests. Our results further elucidate that BME administration has normalized the neurotransmitters (acetylcholine, glutamate, 5 hydroxytryptamine, dopamine, 3,4 dihydroxyphenylacetic acid, norepinephrine) levels that were altered by scopolamine administration in hippocampus of rat brain. BME administration also ameliorated scopolamine effect by down-regulating AChE and up-regulating BDNF, muscarinic M1 receptor and CREB expression in brain hippocampus confirms the potent neuroprotective role and these results are in corroboration with the earlier in vitro studies. BME administration showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant and lipid peroxidation. These results indicate that, cognition-enhancing and neuromodulatory propensity of BME is through modulating the expression of AChE, BDNF, MUS-1, CREB and also by altering the levels of neurotransmitters in hippocampus of rat brain. PMID- 26677079 TI - Assortative Mating for Educational Level in Parents of Public School Children (N > 7000 Individuals) in the Lagos State, Nigeria. AB - Assortative mating for educational level is a widespread phenomenon in Western industrialized societies. However, whether or not the results from Western samples can be generalizable to populations in developing countries in Africa remains to be seen. The present study investigated assortative mating for educational level in parents of public school children (N > 7000) in the Lagos State in Nigeria. Approximately 61.5 % of the parents had spouses at the same level of education. More mothers than fathers married upward in educational level. The assortative mating coefficients for educational level were .52-.61 across respondents' classes, .51-.62 across six school districts, and .57 (.55 .59) in the total sample. Overall, these results were very similar to the findings from Western or Asian samples, providing evidence to support the robustness of human mating pattern in educational attainment across different cultures and ethnic groups. The present findings should be incorporated in future quantitative and molecular genetic studies on Africans. PMID- 26677076 TI - The Lipoxygenases: Their Regulation and Implication in Alzheimer's Disease. AB - Inflammatory processes and alterations of lipid metabolism play a crucial role in Alzheimer's disease (AD) and other neurodegenerative disorders. Polyunsaturated fatty acids (PUFA) metabolism impaired by cyclooxygenases (COX-1, COX-2), which are responsible for formation of several eicosanoids, and by lipoxygenases (LOXs) that catalyze the addition of oxygen to linolenic, arachidonic (AA), and docosahexaenoic acids (DHA) and other PUFA leading to formation of bioactive lipids, significantly affects the course of neurodegenerative diseases. Among several isoforms, 5-LOX and 12/15-LOX are especially important in neuroinflammation/neurodegeneration. These two LOXs are regulated by substrate concentration and availability, and by phosphorylation/dephosphorylation through protein kinases PKA, PKC and MAP-kinases, including ERK1/ERK2 and p38. The protein/protein interaction also is involved in the mechanism of 5-LOX regulation through FLAP protein and coactosin-like protein. Moreover, non-heme iron and calcium ions are potent regulators of LOXs. The enzyme activity significantly depends on the cell redox state and is differently regulated by various signaling pathways. 5-LOX and 12/15-LOX convert linolenic acid, AA, and DHA into several bioactive compounds e.g. hydroperoxyeicosatetraenoic acids (5-HPETE, 12S-HPETE, 15S-HPETE), which are reduced to corresponding HETE compounds. These enzymes synthesize several bioactive lipids, e.g. leucotrienes, lipoxins, hepoxilins and docosahexaenoids. 15-LOX is responsible for DHA metabolism into neuroprotectin D1 (NPD1) with significant antiapoptotic properties which is down-regulated in AD. In this review, the regulation and impact of 5-LOX and 12/15-LOX in the pathomechanism of AD is discussed. Moreover, we describe the role of several products of LOXs, which may have significant pro- or anti-inflammatory activity in AD, and the cytoprotective effects of LOX inhibitors. PMID- 26677077 TI - Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease. AB - In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Muller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID- 26677078 TI - Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina. AB - This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Muller cells. The electroretinogram was used to evaluate retinal functions. Muller cells cultures were prepared from 5- to 7 day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Muller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy. PMID- 26677080 TI - MicroRNA-381 suppresses cell growth and invasion by targeting the liver receptor homolog-1 in hepatocellular carcinoma. AB - MicroRNAs (miRs) have emerged as prospective tools for human cancer therapy, including hepatocellular carcinoma (HCC) therapy. Previous studies have suggested that miR-381 functions as oncogenic or tumor-suppressive miRs in other cancer types. However, the role of miR-381 in HCC remains unknown. The present study investigated the expression and functional role of miR-381 in HCC. miR-381 expression was significantly decreased in HCC tissues and cell lines. miR-381 overexpression significantly inhibited HCC cell proliferation and colony formation, induced G0/G1 cell cycle arrest and suppressed cell invasion. Conversely, suppression of miR-381 showed the opposite effect in HCC cells. Bioinformatics analysis and dual-luciferase reporter assay results showed that miR-381 directly targeted the 3'-untranslated region of liver receptor homolog-1 (LRH-1), and quantitative polymerase chain reaction and western blot analysis results showed that miR-381 negatively modulated LRH-1 expression. Data elucidated that miR-381 directly regulated HCC cell growth and invasion, as well as the Wnt signaling pathways, by targeting LRH-1. Clinical tissue detection data revealed an inverse correlation between miR-381 and LRH-1 expression in HCC tissues, further indicating the functional significance of miR-381-LRH-1 in regulating HCC tumorigenesis. The present study indicates that miR-381 may be a novel tumor suppressor that blocks HCC growth and invasion by targeting LRH-1. The results present novel insights into understanding the molecular mechanism underlying HCC tumorigenesis and provide a future direction to the development of therapeutic interventions for HCC. PMID- 26677081 TI - Development and validation of a highly sensitive LC-MS/MS method for the determination of acacetin in human plasma and its application to a protein binding study. AB - A highly sensitive bioanalytical method for the quantification of acacetin in human plasma was developed and comprehensively validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A minimal volume of human plasma sample (20 MUL) was prepared by simple deproteinization with 80 MUL of acetonitrile. Chromatographic separation was performed using Kinetex C18 column with an isocratic mobile phase consisting of water and acetonitrile (20:80, v/v) containing 0.1 % formic acid at a flow rate of 0.3 mL/min over a total run time of 2.0 min. Mass spectrometric detection was performed using multiple reaction monitoring modes at the mass/charge transitions m/z 285.22 -> 242.17 for acacetin and m/z 277.59 -> 175.04 for chlorpropamide (internal standard). The calibration curve was linear over the range of 0.1-500 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The coefficients of variation for both intra- and inter-day validation were less than 11.9 %, and the intra- and inter-day accuracy ranged from 96.8 to 108 %. Mean recovery of acacetin in human plasma was within the range of 91.5-95.6 %. This validated LC-MS/MS method was successfully applied to a human plasma protein binding study that indicated extensive and concentration-independent protein binding of acacetin in human plasma. PMID- 26677082 TI - Coding of attention across the human intraparietal sulcus. AB - There has been concentrated debate over four decades as to whether or not the nonhuman primate parietal cortex codes for intention or attention. In nonhuman primates, certain studies report results consistent with an intentional role, whereas others provide support for coding of visual-spatial attention. Until now, no one has yet directly contrasted an established motor "intention" paradigm with a verified "attention" paradigm within the same protocol. This debate has continued in both the nonhuman primate and healthy human brain and is subsequently timely. We incorporated both paradigms across two distinct temporal epochs within a whole-parietal slow event-related human functional magnetic resonance imaging experiment. This enabled us to examine whether or not one paradigm proves more effective at driving the neural response across three intraparietal areas. As participants performed saccadic eye and/or pointing tasks, discrete event-related components with dissociable responses were elicited in distinct sub-regions of human parietal cortex. Critically, the posterior intraparietal area showed robust activity consistent with attention (no intention planning). The most contentious area in the literature, the middle intraparietal area produced activation patterns that further reinforce attention coding in human parietal cortex. Finally, the anterior intraparietal area showed the same pattern. Therefore, distributed coding of attention is relatively more pronounced across the two computations within human parietal cortex. PMID- 26677083 TI - Complex Population Patterns of Eunica tatila Herrich-Schaffer (Lepidoptera: Nymphalidae), with Special Emphasis on Sexual Dimorphism. AB - The species Eunica tatila (Herrich-Schaffer) is present in the Neotropical region and comprises three subspecies. In Mexico, only one subspecies is reported: E. t. tatila (Herrich-Schaffer). The Yucatan Peninsula, in southeastern Mexico, is located in a transitional geographical position, between southern Florida, the West Indies and Central America. It is part of a transitional region, important for the dispersion of insects from southern Florida via Cuba and the Yucatan Peninsula. Considering the possibility of the overlapping and delimitation of described subspecies, we sampled different populations in the Yucatan Peninsula to possibly assign a subspecies name and evaluate the magnitude of sexual dimorphism. We collected 591 individuals (?284, ?307) in conserved areas. The study of male genitalia led to the identification of Eunica tatila tatilista (Kaye) as a subspecies; however, hypandrium structure and wing pattern analysis suggest a mix of E. t. tatila and E. t. tatilista characteristics. The analysis of sexual dimorphism provided evidence of more complex wing morphs for females, with 12 patterns instead of four as previously described. Our results demonstrate the complexity of characterizing E. tatila and suggest that the Yucatan Peninsula is a transitional zone for subspecies of some butterflies. PMID- 26677085 TI - Thyroid ultrasound: beyond the diagnosis of thyroid nodules. PMID- 26677084 TI - Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region. AB - The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock. PMID- 26677086 TI - Effect of three months of periodized hydrogymnastics exercise program on urinary concentration of deoxypyridinoline in older women. AB - OBJECTIVE: To determine the effect of three months of periodized hydrogymnastics exercise program on urinary concentration of deoxypyridinoline in older women. SUBJECTS AND METHODS: Twenty-six subjects were randomly assigned in two, intervention group (n = 16) and control group (n = 10). The intervention group followed 12-week of periodized hydrogymnastics training program five times a week, 50 minutes of water exercise with work heart rate reserve of 40-50% (1-6th week) increasing the load to 50-60% (7-12th week); the control group was not involved in exercise and remained sedentary. The urinary concentration of deoxypyridinoline was evaluated by high resolution liquid chromatography using the reactive immulite pyrilinks-D siemens medical solutions, pretest at the baseline and at the end post-test of the 12-week of water-exercise. As statistical analyses mixed 2 x 2 ANOVA was used, also percentage changes (Delta %) was calculated. RESULTS: The results did not show significant improvement (p < 0.05) comparing the interaction intergroup and the measurements of urinary concentration of deoxypyridinoline (p = 0.504), percentage change (Delta %) showed positive improvements in the experimental group of -13.7 (nM/mMcreatine) in comparison with -7.1 (nM/mMcreatine) from the control group. CONCLUSION: The present study involves periodization increasing the load heart rate reserve of hydrogymnastics exercise in order to produce grater adaptations, but the results showed than is not possible to infer that hydrogymnastics is effective in increase urinary concentration of deoxypyridinoline in older women, will be appropriated in the future more studies to better clarify the possibilities of improvements between hydrogymnastics and urinary concentration of deoxypyridinoline. PMID- 26677087 TI - Nonthyroidal illnesses syndrome in full-term newborns with sepsis. AB - OBJECTIVE: To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. MATERIALS AND METHODS: We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. RESULTS: 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. CONCLUSIONS: This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock. PMID- 26677088 TI - The influence of glycemic control on the oral health of children and adolescents with diabetes mellitus type 1. AB - OBJECTIVE: To evaluate the influence of disease control, expressed by the mean values of glycated hemoglobin (HbA1c), in the oral health of children and adolescents with diabetes mellitus type 1 (T1DM). SUBJECTS AND METHODS: A cross sectional study involving 87 children and adolescents (59 girls), 10 +/- 2.6 years old. The participants were divided into three groups: HbA1c <= 8%, 8% < HbA1c <= 10% and HbA1c > 10%. The duration of the disease, age and average HbA1c were obtained from their medical records. Oral health was evaluated according to the following indexes: Simplified Oral Hygiene Index (OHI-S); Community Periodontal Index (CPI); Decayed, Missing or Filled Teeth Index (DMFT/dmft) for permanent and deciduous teeth; and the stimulated salivary flow rate (SSFR). RESULTS: The median SSFR was 1.1 mL/min in the group with HbA1c <= 8%, 0.7 mL/min in the intermediary group and 0.6 mL/min in the HbA1c > 10% group. A significant decrease in salivary flow was observed with an increase in HbA1c (p = 0.007). The DMFT/dmft and CPI indexes were higher in individuals with higher HbA1c values. More caries-free individuals were found in the group with HbA1c <= 8% compared to those with HbA1c > 10%. The group with HbA1c > 10% exhibited more caries and bleeding gums than the other groups. HbA1c values in girls were higher than in boys. CONCLUSION: Children and adolescents with unsatisfactory glycemic control, represented by higher HbA1c concentrations, exhibited a higher frequency of caries and gingivitis, and a reduction in salivary flow. PMID- 26677089 TI - Cardiovascular risk factors and increased carotid intima-media thickness in young patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AB - OBJECTIVE: Increased arterial intima-media thickness has been observed in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21 OHD). CAH has also been associated with obesity, insulin resistance, and hypertension. The aim of the present study was to compare youths with CAH with healthy, normal-weight individuals, evaluating carotid intima-media thickness (CIMT) and indicative factors of cardiovascular risk to seek for abnormalities in the CAH group. SUBJECTS AND METHODS: Clinical, biochemical, and ultrasonographic evaluations, according to published criteria, were performed in 113 subjects (5 to 20 years old): 40 patients with 21-OHD and 73 healthy individuals matched for gender, pubertal status, and age. RESULTS: Most CAH patients were female (80%), salt-losers (72.5%), and pubescent (80%); 10 (25%) patients were overweight. An increase in CIMT was observed both on the right (p = 0.0240) and left (p = 0.0003) sides in 38 CAH patients compared with the healthy individuals. The body mass index, BMI/age Z score, and systolic blood pressure (SBP) were higher in patients compared with controls (p < 0.000 and p = 0.0219, respectively). CONCLUSIONS: Findings of increased CIMT, BMI, and SBP in young patients with 21 OHD indicate the need for early identification and intervention regarding cardiovascular risk. Validating these findings might result in improved therapeutic approaches for children with 21-OHD in the future. PMID- 26677090 TI - Pituitary metastasis of lung neuroendocrine carcinoma: case report and literature review. AB - Metastasis to the pituitary gland is an unusual situation in clinical practice, but the frequency thereof is increasing due to the increased survival of cancer patients, and greater availability of imaging. In most cases, they are found between the sixth and seventh decades of life, as determined in image examination of patients with known malignant neoplasm, but, generally, asymptomatic with respect to pituitary involvement. The most common primary sites are breast in women and lung in men. We present the case of a 64-year-old patient with clinical visual changes, polyuria, polydipsia, and decreased level of consciousness whose tests showed pan-hypopituitarism, hypernatremia and low urine specific gravity, and extensive mass in sellar region. Diabetes insipidus was confirmed and treated, corticotrophic and thyroid deficits were corrected and then the patient underwent resection by transsphenoidal surgery. The histopathological and immunohistochemistry analysis revealed pituitary metastasis of lung neuroendocrine tumor. Subsequently, a chest CT scan showed pulmonary mass consistent with primary neoplasm. Despite the water and electrolyte correction and intravenous glucocorticoid replacement, the patient continued to show decreased level of consciousness due to compression of the brain stem by the pituitary mass, evolving to death. The purpose is to call attention to the differential diagnosis of invasive lesions of the sellar region, mainly in individuals over 50 years and/or when associated with diabetes insipidus, as it may be a case of metastasis, although there is no known primary neoplasm. PMID- 26677091 TI - Psychometric properties of the Parenting Concerns Questionnaire in cancer survivors with minor and young adult children. AB - OBJECTIVE: Although cancer patients with minor children have become more of a focus of psycho-oncological research, little is known about specific parenting concerns. Instruments to assess the concerns and worries of parents with cancer are rare. The Parenting Concerns Questionnaire (PCQ) addresses this issue. We analyzed parenting concerns in cancer survivors and evaluated the German version of the PCQ. METHODS: A total of 1416 cancer survivors with minor and young adult children (<=21 years) were recruited in a register-based study. Descriptive analyses as well as reliability and validity analyses were conducted. We performed a confirmatory factorial analysis of the factor structure proposed by the authors of the original version on the PCQ. RESULTS: Seventy-three percent of the cancer survivors were women, average age was 47.5 years (SD 5.9). Mean time since diagnosis was 44 months (SD 23.4). Between 18 and 31% of survivors reported that they were concerned about their children. The PCQ proved to be a reliable and valid instrument showing medium correlations with standardized measures in expected directions and discriminating between survivors with and without use of psychosocial support services. The factor structure was supported by the confirmatory factorial analysis. CONCLUSIONS: Assessing parenting concerns gives an additional insight into the situation of parents with cancer. In our sample of cancer survivors, we identified one out of three survivors being concerned regarding the impact of their illness on their children. The PCQ can be considered as a valid and reliable instrument with regard to identifying concerned parents with cancer. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26677092 TI - An unprecedented protocol for the synthesis of 3-hydroxy-3-phenacyloxindole derivatives with indolin-2-ones and alpha-substituted ketones. AB - An unprecedented reaction between indolin-2-ones and alpha-substituted ketones has been developed. Using this protocol, a wide range of biologically important 3 hydroxy-3-phenacyloxindole derivatives could be obtained in good yield (up to 93%) under mild reaction conditions. A possible mechanism of this reaction was tentatively proposed based on some control experiments and MS spectrometry analysis. PMID- 26677093 TI - RhD negativity among pregnant women in multiethnic Suriname. AB - BACKGROUND: RhD negativity is distributed unevenly among different ethnicities. In this study we explored the frequencies of RhD negativity in pregnant women in multiethnic Suriname, along with screening results for red blood cell (RBC) antibodies in these women and their offspring. Results may help identify women at risk for hemolytic disease of the fetus and newborn. STUDY DESIGN AND METHODS: A retrospective study was performed in pregnant women who delivered at three major hospitals in Suriname between January 1, 2013, and December 31, 2014. RESULTS: The overall prevalences of RhD negativity among 8686 women was 4.3%. The percentages of RhD negativity in Maroons, Creoles, and Hindustani women were 7.2, 5.4, and 3.7%, respectively. Chinese and Javanese women had very low prevalences of 0.8 and 0.5%, respectively, and Amerindians showed no RhD negativity. Antibody screening was positive in six D- (five Maroons and one Creole) women and weakly positive in three women (two Creoles and one Maroon), making overall antibody prevalence 4.4%. In 15 (5.5%; 10 Maroons, four Creoles, one Chinese) newborns from D- mothers antibody screening was positive. CONCLUSION: In the multiethnic Surinamese population RhD negativity among pregnant women varied between 0.0 and 7.2% between ethnic groups. RBC antibodies were detected during pregnancy and in newborns in 4.4 and 5.5%, respectively. PMID- 26677094 TI - Hemosporidian parasites of free-living birds in the Sao Paulo Zoo, Brazil. AB - Numerous studies addressed the diversity of bird Plasmodium and Haemoproteus parasites. However, a few have been carried out in continental avian hotspot regions such as Brazil, a country with markedly different biomes, including Amazon, Brazilian Savanna, Atlantic Forest, Caatinga, Pantanal, and Pampas. We present the first study on hemosporidian (Haemosporida) parasites in free-living birds from an Atlantic Forest fragment where more than 80 avian species have been reported. Within this area, the Sao Paulo Zoo locates, and it is the fourth largest zoo in the world and the largest in Latin America. A total of 133 free living bird samples representing 12 species were collected in the zoo, with the overall hemosporidian prevalence of 18 % by PCR-based diagnostics. Twenty-four positive PCR signals were reported from four different bird species, including migratory ones. Columba livia, an urban species, considered nowadays a pest in big cities, showed 100 % prevalence of Haemoproteus spp., mainly Haemoproteus columbae. We discuss the epidemiological importance of new parasites introduced by migratory birds in the Sao Paulo Zoo area and the risk it poses to the captive species, which are natives or exotics. We also warn about the influence these parasites can have on the biodiversity and the structure of host populations by altering the competitive interaction between the free-living and the captive birds. PMID- 26677095 TI - Molecular characterisation of Sarcocystis bovifelis, Sarcocystis bovini n. sp., Sarcocystis hirsuta and Sarcocystis cruzi from cattle (Bos taurus) and Sarcocystis sinensis from water buffaloes (Bubalus bubalis). AB - About 200 individual sarcocysts were excised from 12 samples of cattle beef from five countries (Argentina, Brazil, Germany, New Zealand, Uruguay) and tentatively identified to species or cyst type on the basis of their size and shape and cyst wall morphology. Genomic DNA was extracted from 147 of these sarcocysts and used initially for PCR amplification and sequencing of the partial mitochondrial cytochrome c oxidase subunit I gene (cox1) in order to identify the sarcocysts to species and/or sequence type. In addition, seven Sarcocystis sinensis-like sarcocysts collected from the oesophagus of water buffaloes in Egypt were examined at cox1 for comparative purposes. Based on the results from the cox1 marker, selected sarcocyst isolates from both hosts were further characterised at one to three regions of the nuclear ribosomal (r) DNA unit, i.e. the complete 18S rRNA gene, the complete internal transcribed spacer 1 (ITS1) region and the partial 28S rRNA gene. This was done in order to compare the results with previous molecular identifications based on 18S rRNA gene sequences and to evaluate the utility of these regions for species delimitations and phylogenetic inferences. On the basis of sarcocyst morphology and molecular data, primarily the cox1 sequences, four Sarcocystis spp. were identified in the samples of cattle beef. Twenty-two microscopic sarcocysts (1 * 0.1 mm) with hair-like protrusions were assigned to Sarcocystis cruzi, 56 macroscopic sarcocysts (3-8 * 0.5 mm) with finger-like protrusions were assigned to Sarcocystis hirsuta and 45 and 24 microscopic sarcocysts (1-3 * 0.1-0.2 mm) with finger-like protrusions were assigned to Sarcocystis bovifelis and Sarcocystis bovini n. sp., respectively. Sarcocysts of S. cruzi were identified in samples of beef from Argentina and Uruguay; sarcocysts of S. hirsuta in samples from Argentina, Brazil, Germany and New Zealand; sarcocysts of S. bovifelis in samples from Argentina and Germany; and sarcocysts of S. bovini in samples from Argentina and New Zealand. The microscopic sarcocysts from water buffaloes were confirmed to belong to S. sinensis. The cox1 sequences of S. bovifelis and S. bovini, respectively, shared an identity of 93-94 % with each other, and these sequences shared an identity of 89-90 % with cox1 of S. sinensis. In contrast, the intraspecific sequence identity was 98.4-100 % (n = 45), 99.3-100 % (n = 24) and 99.5-100 % (n = 7) for sequences of S. bovifelis, S. bovini and S. sinensis, respectively. In each of the latter three species, an aberrant type of cox1 sequences was also identified, which was only 91-92 % identical with the predominant cox1 type of the same species and about 98 % identical with the aberrant types of the two other species. These aberrant cox1 sequences are believed to represent non-functional nuclear copies of the mitochondrial genes (numts or pseudogenes). They might be used as additional markers to separate the three species from each other. Sequencing of a considerable number of clones of S. bovifelis, S. bovini and S. sinensis from each of the three regions of the rDNA unit revealed intraspecific sequence variation in all loci in all species and particularly in the ITS1 locus (78-100 % identity). As regards the 18S rRNA gene, it was possible to separate the three species from each other on the basis of a few consistent nucleotide differences in the less variable 3' end half of the gene. A comparison of the new sequences with GenBank sequences obtained from S. sinensis-like sarcocysts in cattle in other studies indicated that previous sequences derived from cattle in Germany and Austria belonged to S. bovifelis, whereas those derived from cattle in China belonged to S. bovini. On the basis of the new 28S rRNA sequences, it was possible to separate S. sinensis from S. bovifelis and S. bovini, whereas the latter two species could not be separated from each other. Based on ITS1 sequences, the three species were indistinguishable. Phylogenetic analysis using maximum parsimony placed with fairly high support cox1 sequences of S. bovifelis, S. bovini and S. sinensis, respectively, into three monophyletic clusters, with S. bovifelis and S. bovini being a sister group to S. sinensis. In contrast, phylogenies based on each of the three regions of the rDNA unit did not separate sequences of the three species completely from each other. Characterisation of cox1 of 56 isolates of S. hirsuta from four countries revealed only 13 haplotypes and an intraspecific sequence identity of 99.3-100 %. In the three regions of the rDNA unit, there was more extensive sequence variation, particularly in the ITS1 region. The 22 cox1 sequences of S. cruzi displayed a moderate intraspecific variation (98.6-100 %), whereas there was no variation at the 18S rRNA gene among 10 sequenced isolates. Sequencing of 16 clones of the partial 28S rRNA gene of S. cruzi yielded two markedly different sequence types, having an overall sequence identity of 95-100 %. PMID- 26677096 TI - Excretory system of representatives from family Diplozoidae (Monogenea). AB - Diplozoons are representatives of blood-feeding ectoparasites from the family Diplozoidae (Polyopisthocotylea, Monogenea). Although these worms have been the subject of numerous taxonomical, phylogenetic, and ecological studies, the detailed study of their excretory system has remained relatively neglected. Our observations focused on the morphological and ultrastructural features of the excretory apparatus of four diplozoid species: Diplozoon paradoxum, Eudiplozoon nipponicum, Paradiplozoon bliccae, and Paradiplozoon homoion. Observations were obtained using two microscope methods: light microscopy, equipped with differential interference contrast (Nomarski DIC) and transmission electron microscopy (TEM). The ultrastructure of two basic compartments which forms the excretory apparatus, flame cells with filtration apparatus, and canal cells forming the protonephridial ducts is revealed in this study. A unique consecutive sequence of longitudinal semi-thin sections of the excretory pore of E. nipponicum is visualized there for the first time. PMID- 26677097 TI - Sarcocystis tuagulusi, n.sp. (Apicomplexa: Sarcocystidae) from Williamson's mouse deer (Tuagulus williamsoni) (Artiodactyla:Tragulidae). AB - Numerous species of Sarcocystis have been reported from wild ruminants, but none has been from Williamson's mouse deer (Tuagulus williamsoni). Here, we describe a new species, Sarcocystis tuagulusi, infecting five of 12 Williamson's mouse deer from southwest China. Mature sarcocysts are microscopic, up to 2280-MUm long. The sarcocyst wall had 8.2-MUm long villar protrusions, type 24. Using transmission electron microscopy, the protrusions on sarcocysts appeared as elongated, lancet- or leaf-like shapes in longitudinal sections; in contrast, the cross-sections revealed mushroom-shaped protrusions. In the core of the protrusion, a bundle of microtubules penetrated diagonally into a ground substance along the longitudinal axis. A phyogenetic analysis based on 18S rRNA and cox1 sequences suggested S. tuagulusi is closely related to Sarcocystis species from ruminants that employ felids as definitive hosts. PMID- 26677099 TI - Highly Porous Materials with Unique Mechanical Properties from Smart Capillary Suspensions. AB - Smart capillary suspensions are used to fabricate macroporous solids with unique features regarding porosity and mechanical strength from a wide range of materials, including carbon layers and polyethylene membranes, even if sintering or high-temperature treatment is not feasible. High-strength porous ceramics are obtained, tailoring neck and pore shape via controlled deposition of fine particles at the sintering necks. PMID- 26677098 TI - Application of biogenic carbon dioxide produced by yeast with different carbon sources for attraction of mosquitoes towards adult mosquito traps. AB - Surveillance is a prime requisite for controlling arthropod vectors like mosquitoes that transmit diseases such as malaria, dengue and chikungunya. Carbon dioxide (CO2) is one of the main cues from vertebrate breath that attracts mosquitoes towards the host. Hence, CO2 is used as an attractant during surveillance of mosquitoes either from commercial cylinders or dry ice for mosquito traps. In the present study, the biogenic carbon dioxide production was optimized with different carbon sources such as glucose, simple sugar and jaggery with and without yeast peptone dextrose (YPD) media using commercial baker's yeast. The results showed that yeast produced more biogenic CO2 with simple sugar as compared to other carbon sources. Further substrate concentration was optimized for the continuous production of biogenic CO2 for a minimum of 12 h by using 10 g of baker's yeast with 50 g of simple sugar added to 1.5 l distilled water (without YPD media) in a 2-l plastic bottle. This setup was applied in field condition along with two different mosquito traps namely Mosquito Killing System (MKS) and Biogents Sentinel (BGS) trap. Biogenic CO2 from this setup has increased the trapping efficiency of MKS by 6.48-fold for Culex quinquefasciatus, 2.62-fold for Aedes albopictus and 1.5-fold for Anopheles stephensi. In the case of BGS, the efficiency was found to be increased by 3.54-fold for Ae. albopictus, 4.33-fold for An. stephensi and 1.3-fold for Armigeres subalbatus mosquitoes. On the whole, plastic bottle setup releasing biogenic CO2 from sugar and yeast has increased the efficiency of MKS traps by 6.38-fold and 2.74-fold for BGS traps as compared to traps without biogenic CO2. The present study reveals that, among different carbon sources used, simple sugar as a substance (which is economical and readily available across the world) yielded maximum biogenic CO2 with yeast. This setup can be used as an alternative to CO2 cylinder and dry ice in any adult mosquito traps to enhance their trapping efficiency of a mosquito surveillance programme. PMID- 26677100 TI - Contact-assisted protein structure modeling by global optimization in CASP11. AB - We have applied the conformational space annealing method to the contact-assisted protein structure modeling in CASP11. For Tp targets, where predicted residue residue contact information was provided, the contact energy term in the form of the Lorentzian function was implemented together with the physical energy terms used in our template-free modeling of proteins. Although we observed some structural improvement of Tp models over the models predicted without the Tp information, the improvement was not substantial on average. This is partly due to the inaccuracy of the provided contact information, where only about 18% of it was correct. For Ts targets, where the information of ambiguous NOE (Nuclear Overhauser Effect) restraints was provided, we formulated the modeling in terms of the two-tier optimization problem, which covers: (1) the assignment of NOE peaks and (2) the three-dimensional (3D) model generation based on the assigned NOEs. Although solving the problem in a direct manner appears to be intractable at first glance, we demonstrate through CASP11 that remarkably accurate protein 3D modeling is possible by brute force optimization of a relevant energy function. For 19 Ts targets of the average size of 224 residues, generated protein models were of about 3.6 A Calpha atom accuracy. Even greater structural improvement was observed when additional Tc contact information was provided. For 20 out of the total 24 Tc targets, we were able to generate protein structures which were better than the best model from the rest of the CASP11 groups in terms of GDT-TS. Proteins 2016; 84(Suppl 1):189-199. (c) 2015 Wiley Periodicals, Inc. PMID- 26677101 TI - The Role of Bone Scintigraphy in the Diagnosis of Calciphylaxis. PMID- 26677103 TI - Interventions for treating traumatised ankylosed permanent front teeth. AB - BACKGROUND: Teeth that have suffered trauma can fuse to the surrounding bone in a process called dental ankylosis. Ankylosed permanent front teeth fail to erupt during facial growth and can become displaced, thus resulting in functional and aesthetic problems. Dental ankylosis is also associated with root resorption, which may eventually lead to the loss of affected teeth. Different interventions for the management of ankylosed permanent front teeth have been described, but it is unclear which are the most effective. OBJECTIVES: To evaluate the effectiveness of any intervention that can be used in the treatment of ankylosed permanent front teeth. SEARCH METHODS: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 3 August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 7), MEDLINE via OVID (1946 to 3 August 2015), EMBASE via OVID (1980 to 3 August 2015) and LILACS via BIREME (1982 to 3 August 2015). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any intervention for treating displaced ankylosed permanent front teeth in individuals of any age. Treatments could be compared with one another, with placebo or with no treatment. DATA COLLECTION AND ANALYSIS: Two independent review authors screened studies independently. Full papers were obtained for potentially relevant trials. Although no study was included, the authors had planned to extract data independently and to analyse the data according to the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: No randomised controlled trials that met the inclusion criteria were identified. AUTHORS' CONCLUSIONS: We were unable to identify any reports of randomised controlled trials regarding the efficacy of different treatment options for ankylosed permanent front teeth. The lack of high level evidence for the management of this health problem emphasises the need for well designed clinical trials on this topic, which conform to the CONSORT statement (www.consort statement.org/). PMID- 26677102 TI - Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway. AB - It is known that prolonged glucocorticoid (GC) treatment results in osteoporosis. This study aimed to evaluate the protective effects of curcumin on the bones of rats with dexamethasone (DXM)-induced osteoporosis. In the present study, rats were administered DXM for 60 days to induce osteoporosis, and they were then treated with curcumin (100 mg/kg/day) for a further 60 days. H&E staining was used to observe the pathological changes in the femurs. Serum osteocalcin levels and collagen-type I fragments (CTX) were examined as bone metabolism markers. The results revealed that treatment with curcumin attenuated DXM-induced bone injury in femurs, increased the serum levels of osteocalcin and decreased the levels of CTX. In addition, in in vitro experiments, primary rat osteoblasts treated with curcumin at 0.5, 1 and 2 uM were exposed to 100 nM DXM. An MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase activity, and the mRNA expression levels of runt-related transcription factor 2 (Runx2), osterix, osteocalcin, collagen, type 1, alpha 1 (Col1A1) and osteonectin were detected to assess transcription factor-associated osteogenic differentiation. The mRNA and protein expression levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappa B ligand (RANKL) were detected to assess cytokine-associated osteoclastogenesis. The results demonstrated that curcumin prevented the DXM-induced inhibition of the proliferative ability of the osteoblasts in a dose-dependent manner. In addition, curcumin upregulated the mRNA expression levels of transcription factors that favor osteoblast differentiation and increased the ratio of OPG to RANKL. Moreover, the effects of curcumin on the Wnt signaling pathway were also investigated. RT-qPCR and western blot analysis demonstrated that the Wnt signaling pathway, which was inhibited by DXM, was re-activated upon treatment with curcumin. Immunofluorescence staining revealed that curcumin restored the intranuclear staining of beta-catenin in the DXM-stimulated osteoblasts. Collectively, our data demonstrate that curcumin may be a potential therapeutic agent for the treatment of GC-induced osteoporosis. PMID- 26677104 TI - Chelidonine induces mitotic slippage and apoptotic-like death in SGC-7901 human gastric carcinoma cells. AB - The aim of the present study was to investigate the effect of chelidonine on mitotic slippage and apoptotic-like death in SGC-7901 human gastric cancer cells. The MTT assay was performed to detect the antiproliferative effect of chelidonine. Following treatment with chelidonine (10 umol/l), the ultrastructure changes in SGC-7901, MCF-7 and HepG2 cells were observed by transmission electron microscopy. The effects of chelidonine on G2/M phase arrest and apoptosis of SGC 7901 cells were determined by flow cytometry. Indirect immunofluorescence assay and laser scanning confocal microscopy (LSCM) were used to detect the phosphorylation level of histone H3 (Ser10) and microtubule formation was detected using LSCM following immunofluorescent labeling. Subsequent to treatment with chelidonine (10 umol/l), expression levels of mitotic slippage-associated proteins, including BUB1 mitotic checkpoint serine/threonine kinase B (BubR1), cyclin-dependent kinase 1 (Cdk1) and cyclin B1, and apoptosis-associated protein, caspase-3 were examined by western blotting at 24, 48 and 72 h. The half maximal inhibitory concentration of chelidonine was 23.13 umol/l over 48 h and chelidonine induced G2/M phase arrest of cells. The phosphorylation of histone H3 at Ser10 was significantly increased following treatment with chelidonine for 24 h, indicating that chelidonine arrested the SGC-7901 cells in the M phase. Chelidonine inhibited microtubule polymerization, destroyed microtubule structures and induced cell cycle arrest in the M phase. Giant cells were observed with multiple micronuclei of varying sizes, which indicated that following a prolonged arrest in the M phase, the cells underwent mitotic catastrophe. Western blotting demonstrated that the protein expression levels of BubR1, cyclin B1 and Cdk1 decreased significantly between 48 and 72 h. Low expression levels of BubR1 and inactivation of the cyclin B1-Cdk1 complex results in the cells being arrested at mitosis and leads to mitotic slippage. In addition, apoptotic morphological changes in multinucleated cells were observed, the apoptosis rates increased gradually with administration of chelidonine in a time-dependent manner and the protein levels of caspase-3 increased significantly between 24 and 72 h. Thus, chelidonine induces mitotic slippage, and apoptotic like death occurs in SGC-7901 cells undergoing mitotic catastrophe. Gastric cancer is a common malignancy, and ranks second in overall cancer-associated mortalities worldwide. The present study demonstrated that chelidonine induces M phase arrest and mitotic slippage of SGC-7901 human gastric carcinoma cells via downregulating the expression of BubR1, Cdk1 and cyclin B1 proteins. With the prolongation of chelidonine treatment, the giant cells with multiple micronuclei underwent mitotic slippage and were maintained in the G1 phase and did not survive. A number of multinucleated cells underwent apoptosis via a caspase dependent signaling pathway. The current study proposes that chelidonine induces mitotic slippage and apoptotic-like death of SGC-7901 cells. PMID- 26677106 TI - CRMP-5 interacts with actin to regulate neurite outgrowth. AB - CRMP family proteins (CRMPs) are abundantly expressed in the developing nervous system mediating growth cone guidance, neuronal polarity and axon elongation. CRMP-5 has been indicated to serve a critical role in neurite outgrowth. However, the detailed mechanisms of how CRMP-5 regulates neurite outgrowth remain unclear. In the current study, co-immunoprecipitation was used to identify the fact that CRMP-5 interacted with the actin and tubulin cytoskeleton networks in the growth cones of developing hippocampal neurons. CRMP-5 exhibited increased affinity towards actin when compared with microtubules. Immunocytochemistry was used to identify the fact that CRMP-5 colocalized with actin predominantly in the C domain and T-zone in growth cones. In addition, genetic inhibition of CRMP-5 by siRNA suppressed the expression of actin, growth cone development and neurite outgrowth. Overexpression of CRMP-5 promoted the interaction with actin, growth cone development and hippocampal neurite outgrowth. Taken together, these data suggest that CRMP-5 is able to interact with the actin cytoskeleton network in the growth cone and affect growth cone development and neurite outgrowth via this interaction in developing hippocampal neurons. PMID- 26677107 TI - Effect of long-range repulsive Coulomb interactions on packing structure of adhesive particles. AB - The packing of charged micron-sized particles is investigated using discrete element simulations based on adhesive contact dynamic model. The formation process and the final obtained structures of ballistic packings are studied to show the effect of interparticle Coulomb force. It is found that increasing the charge on particles causes a remarkable decrease of the packing volume fraction phi and the average coordination number , indicating a looser and chainlike structure. Force-scaling analysis shows that the long-range Coulomb interaction changes packing structures through its influence on particle inertia before they are bonded into the force networks. Once contact networks are formed, the expansion effect caused by repulsive Coulomb forces are dominated by short-range adhesion. Based on abundant results from simulations, a dimensionless adhesion parameter Ad*, which combines the effects of the particle inertia, the short range adhesion and the long-range Coulomb interaction, is proposed and successfully scales the packing results for micron-sized particles within the latest derived adhesive loose packing (ALP) regime. The structural properties of our packings follow well the recent theoretical prediction which is described by an ensemble approach based on a coarse-grained volume function, indicating some kind of universality in the low packing density regime of the phase diagram regardless of adhesion or particle charge. Based on the comprehensive consideration of the complicated inter-particle interactions, our findings provide insight into the roles of short-range adhesion and repulsive Coulomb force during packing formation and should be useful for further design of packings. PMID- 26677108 TI - Putative bacterial interactions from metagenomic knowledge with an integrative systems ecology approach. AB - Following the trend of studies that investigate microbial ecosystems using different metagenomic techniques, we propose a new integrative systems ecology approach that aims to decipher functional roles within a consortium through the integration of genomic and metabolic knowledge at genome scale. For the sake of application, using public genomes of five bacterial strains involved in copper bioleaching: Acidiphilium cryptum, Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, Leptospirillum ferriphilum, and Sulfobacillus thermosulfidooxidans, we first reconstructed a global metabolic network. Next, using a parsimony assumption, we deciphered sets of genes, called Sets from Genome Segments (SGS), that (1) are close on their respective genomes, (2) take an active part in metabolic pathways and (3) whose associated metabolic reactions are also closely connected within metabolic networks. Overall, this SGS paradigm depicts genomic functional units that emphasize respective roles of bacterial strains to catalyze metabolic pathways and environmental processes. Our analysis suggested that only few functional metabolic genes are horizontally transferred within the consortium and that no single bacterial strain can accomplish by itself the whole copper bioleaching. The use of SGS pinpoints a functional compartmentalization among the investigated species and exhibits putative bacterial interactions necessary for promoting these pathways. PMID- 26677110 TI - A Rapid and Versatile Assay for Ago2-Mediated Cleavage by Using Branched Rolling Circle Amplification. AB - Micro RNA (miRNA) research has evolved into an essential part of investigating gene regulation in which deregulation of numerous miRNAs is associated with various cellular dysfunction and diseases. Here, we describe a rapid and homogenous assay for Ago2-mediated target RNA cleavage, based on branched rolling circle amplification (BRCA). In particular, the ability to investigate small molecule binders for inhibition of miRNA function is within the potential of our assay. This method uses no artificial fluorescence labeling of RNA components, which can be an advantage in screening of potential inhibitors. To visualize cleavage of RNA substrate by Ago2, we developed a two-step assay composed of Ago2 mediated cleavage and BRCA-based detection. The assay is cost-effective and practicable and can be performed in 96-well format by using a standard qPCR machine. PMID- 26677111 TI - Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio). AB - Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 betaestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017. PMID- 26677109 TI - Immune Mechanisms of Chronic Rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a common inflammatory disease that results in a significant decrease in patient quality of life and a large economic burden. However, the lack of population-based epidemiologic studies and robust model systems has made it difficult to fully elucidate the key inflammatory pathways that drive the chronic inflammatory responses observed in CRS. This review will highlight the wide variety of factors that likely contribute to CRS disease pathogenesis. Defects in the innate immune function of the airway epithelium, including decreases in barrier function, mucociliary clearance, and production of antimicrobial peptides, all likely play a role in the initial inflammatory response. Subsequent recruitment and activation of eosinophils, mast cells, and innate lymphoid cells (ILCs) further contributes to the chronic inflammatory response and directly activates adaptive immune cells, including T and B cells. However, development of new tools and model systems is still needed to further understand the chronicity of this inflammatory response and which specific factors are necessary or sufficient to drive CRS pathogenesis. Such studies will be critical for the development of improved therapeutic strategies aimed at treating this highly prevalent and costly disease. PMID- 26677112 TI - Discriminating long myelitis of neuromyelitis optica from sarcoidosis. AB - OBJECTIVE: To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS). METHODS: We identified adult patients evaluated between 1996 and 2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning >=3 vertebral segments. All NMOSD patients were positive for aquaporin-4 immunoglobulin G, and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated. Spine magnetic resonance imaging was reviewed by 2 neuroradiologists. RESULTS: We studied 71 patients (NMOSD, 37; SCS, 34). Sixteen (47%) SCS cases were initially diagnosed as NMOSD or idiopathic transverse myelitis. Median delay to diagnosis was longer for SCS than NMOSD (5 vs 1.5 months, p < 0.01). NMOSD myelitis patients were more commonly women, had concurrent or prior optic neuritis or intractable vomiting episodes more frequently, had shorter time to maximum deficit, and had systemic autoimmunity more often than SCS (p < 0.05). SCS patients had constitutional symptoms, cerebrospinal fluid (CSF) pleocytosis, and hilar adenopathy more frequently than NMOSD (p < 0.05); CSF hypoglycorrhachia (11%, p = 0.25) and elevated angiotensin converting enzyme (18%, p = 0.30) were exclusive to SCS. Dorsal cord subpial gadolinium enhancement extending >=2 vertebral segments and persistent enhancement >2 months favored SCS, and ringlike enhancement favored NMOSD (p < 0.05). Maximum disability was similar in both disorders. INTERPRETATION: SCS is an under-recognized cause of longitudinally extensive myelitis that commonly mimics NMOSD. We identified clinical, laboratory, systemic, and radiologic features that, taken together, help discriminate SCS from NMOSD. PMID- 26677113 TI - 5-azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. AB - Hepatocyte cell adhesion molecule (hepaCAM), a tumor-suppressor gene, is rarely expressed in bladder carcinoma. However, little is known concerning the mechanisms of low hepaCAM expression in bladder cancer. Abnormal hypermethylation in the promoter plays a crucial role in cancer by silencing tumor-suppressor genes, which is catalyzed by DNA methyltransferases (DNMTs). In the present study, a total of 31 bladder cancer and 22 adjacent tissues were assessed by immunohistochemistry to detect DNMT3A/3B and hepaCAM expression. Methylation of hepaCAM was determined by methylation-specific polymerase chain reaction (MSP). The mRNA and protein levels of DNMT3A/3B and hepaCAM were determined by RT-PCR and western blot analysis after treatment with 5-azacytidine (AZAC). Following AZAC treatment, the proliferation of bladder cancer cells was detected by CCK-8 and colony formation assays. Cell cycle distribution was examined by flow cytometry. To further evaluate the tumor-suppressive roles of AZAC and the involved mechanisms, the anti-tumorigenicity of AZAC was tested in vivo. The expression of DNMT3A/3B protein was markedly increased in the bladder carcinoma tissues (P<0.05), and had a negative linear correlation with hepaCAM expression in the same patients according to Pearson's analysis (r=-0.7176/-0.7127, P<0.05). The MSP results indicated that the hepaCAM gene was hypermethylated in three bladder cancer cell lines. Furthermore, we found that downregulation of DNMT3A/3B expression, after treatment with AZAC, reversed the hypermethylation and expression of hepaCAM in bladder cancer cells. In addition, AZAC inhibited the proliferation of bladder cancer cells and arrested cells at the G0/G1 phase. The in vivo results showed that expression of DNMT3A/3B and hepaCAM as well as tumor growth of nude mice were markedly altered which corresponded with the in vitro results. Due to the ability to reactivate expression of hepaCAM and inhibit growth of bladder cancer cells, AZAC may represent an effective treatment for bladder cancer. PMID- 26677114 TI - Affective learning in adults with intellectual disability: an experiment using evaluative conditioning. AB - BACKGROUND: Evaluative conditioning is a form of affective learning in which initially neutral stimuli acquire an affective value through association with negative or positive stimuli. Recent research shows an important role for cognitive resources in this type of learning. This form of affective learning has rarely been studied in intellectual disability (ID). METHOD: We examined evaluative conditioning in 16 adults with mild to moderate ID compared to age- and gender-matched control participants. Neutral shapes and symbols were repeatedly paired with positive, neutral or negative unconditioned stimuli (faces or International Affective Picture System images). There was also an extinction phase. RESULTS: There was significant acquisition of conditioning in both groups. Stimuli paired with positive images were evaluated more positively, and stimuli paired with negative images were evaluated more negatively. Post-extinction ratings however show that these novel affective associations were not maintained by individuals with ID as much as by individuals in the control group. CONCLUSIONS: We conclude that ID modulates some aspects of affective learning but not necessarily initial preference acquisition. PMID- 26677116 TI - Arquivos de Neuro-Psiquiatria in the Brazilian Academy of Neurology: natural evolution. PMID- 26677115 TI - Assessment of the Protein-Protein Interactions in a Highly Concentrated Antibody Solution by Using Raman Spectroscopy. AB - PURPOSE: To investigate the protein-protein interactions of a highly concentrated antibody solution that could cause oligomerization or aggregation and to develop a better understanding of the optimization of drug formulations. METHODS: In this study, we used Raman spectroscopy to investigate the structure and interactions of a highly concentrated antibody solution over a wide range of concentrations (10-200 mg/mL) with the aid of a multivariate analysis. RESULTS: Our analysis of the amide I band, I 856 /I 830 of Tyr, and the relative intensity at 1004 cm(-1) of the Phe and OH stretching region at around 3000 cm(-1) showed that across this wide range of concentrations, the secondary structure of the IgG molecules did not change; however, short-range attractive interactions around the Tyr and Phe residues occurred as the distance between the IgG molecules decreased with increasing concentration. Analysis of the OH stretching region at around 3000 cm( 1) showed that these short-range attractive interactions correlated with the amount of hydrated water around the IgG molecules. CONCLUSIONS: Our data show that Raman spectroscopy can provide valuable information of the protein-protein interactions based on conformational approaches to support conventional colloidal approaches, especially for analyses of highly concentrated solutions. PMID- 26677117 TI - Diagnosis of limb-girdle muscular dystrophies in the molecular biology era: do clinical findings still matter? PMID- 26677118 TI - Limb-girdle muscular dystrophy type 2A in Brazilian children. AB - Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A) caused by mutations in CAPN3 gene. OBJECTIVE: To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. METHOD: We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. RESULTS: All patients were female (three to 12 years). The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. CONCLUSION: In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder. PMID- 26677119 TI - Facial diplegia: etiology, clinical manifestations, and diagnostic evaluation. AB - OBJECTIVE: Facial diplegia (FD) is a rare neurological manifestation with diverse causes. This article aims to systematically evaluate the etiology, diagnostic evaluation and treatment of FD. METHOD: The study was performed retrospectively and included 17 patients with a diagnosis of FD. RESULTS: Patients were diagnosed with Guillain-Barre syndrome (GBS) (11), Bickerstaff's brainstem encephalitis (1), neurosarcoidosis (1), non-Hodgkin's Lymphoma (1), tuberculous meningitis (1) herpes simplex reactivation (1) and idiopathic (1). In addition, two patients had developed FD during pregnancy. CONCLUSION: Facial diplegia is an ominous symptom with widely varying causes that requires careful investigation. PMID- 26677120 TI - Hackathon as a way to raise awareness and foster innovation for stroke. AB - The 'Time is Brain" concept has been a major focus in the World Stroke Awareness Campaign. OBJECTIVE: We describe our experience with a Hackathon (junction of hack+marathon), a 24 hour event of innovation- and technology-based project development, focused around detecting stroke. METHOD: The Hackathon was held during a Brazilian Student's union (BRASA) congress involving students from engineering and other technological disciplines. RESULTS: Four teamscompleted the 24-hour challenge; two teams opted the stroke challenge. One team proposed improving detection using a mobile sensor Fit-Bit combined with a smart-phone to contact emergency dispatch. The other team developed a game, in which kids would play a role as a neurologist; to diagnosis stroke with objective to increase awareness. CONCLUSION: Hackathons can focus attention on innovation and improvement opportunities to support the World Stroke Campaign, as well as other campaigns to raise awareness for other health or social problems. PMID- 26677121 TI - Headache-related disability among medical students in Amazon: a cross-sectional study. AB - OBJECTIVE: To evaluate the prevalence of headache in medical students, and quantify the degree of disability through HIT-6 and MIDAS SCALE. METHOD: The criteria established by International Headache Society were used and the HIT-6 and MIDAS, to asses disability. RESULTS: 140 medical students from UFAM were evaluated. 16.43% cases of migraine headache, 6.43% of probable migraine, and 23.57% of tension headaches were detected. 6.42% reported an absence of headache; and another 11.42% had secondary headache. According to the HIT-6 questionnaire, in 7.14% and 18.57% of the students, headaches were classified as having substantial to severe impact, respectively. CONCLUSION: Migraine and probable migraine had higher scores than the other types of headache and, therefore, led to higher levels of disability. The present study did not find a significant correlation between student semester, age or extracurricular activities on the impact generated by headache. PMID- 26677122 TI - Longer epilepsy duration and multiple lobe involvement predict worse seizure outcomes for patients with refractory temporal lobe epilepsy associated with neurocysticercosis. AB - OBJECTIVE: To investigate the surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) and neurocysticercosis (NCC). METHODS: A retrospective investigation of patients with TLE-HS was conducted in a tertiary center. RESULTS: Seventy-nine (62.2%), 37 (29.1%), 6 (4.7%), and 5 (3.9%) patients were Engel class I, II, III, and IV, respectively. Fifty-two (71.2%) patients with epilepsy durations <= 10 years prior to surgery were seizure-free 1 year after the operation compared to 27 (50.0%) patients with epilepsy durations > 10 years (p = 0.0121). Forty-three (72.9%) patients with three or fewer lobes affected by NCC were seizure-free one year after the operation, and 36 (52.9%) patients with more than three involved lobes were seizure-free after surgery (p = 0.0163). CONCLUSIONS: Longer epilepsy durations and multiple lobe involvement predicted worse seizure outcomes in TLE-HS plus NCC patients. PMID- 26677123 TI - Surgical technique of retrograde ventricle-sinus shunt is an option for the treatment of hydrocephalus in infants after surgical repair of myelomeningocele. AB - INTRODUCTION: Treatment of hydrocephalus is accomplished primarily through a ventricular-peritoneal shunt (VPS). This study aims to describe the application of retrograde ventricle-sinus shunt (RVSS) in patients with hydrocephalus after surgical treatment of myelomeningocele. METHOD: A prospective, randomized and controlled pilot study. We consecutively enrolled 9 patients with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012. These patients underwent elective RVSS or VPS. Five underwent RVSS and 4 underwent VPS. Patients were followed for one year with quarterly evaluations and application of transcranial Doppler. RESULTS: RVSS group showed outcomes similar to those of VPS group. Doppler revealed significant improvement when comparing preoperative to postoperative period. RVSS group had significantly higher cephalic perimeter than VPS group. Neuropsychomotor development, complications and subjective outcomes did not differ between groups. CONCLUSION: RVSS shunt is viable; it is an alternative option for the treatment of hydrocephalus. PMID- 26677124 TI - Recombinant expression, purification, and characterization of an acyl-CoA binding protein from Aspergillus oryzae. AB - OBJECTIVES: To characterize biochemically the lipid metabolism-regulating acyl CoA binding protein (ACBP) from the industrially-important fungus Aspergillus oryzae. RESULTS: A full-length cDNA encoding a candidate ACBP from A. oryzae (AoACBP) was cloned and expressed in Escherichia coli as a maltose-binding protein (MBP) fusion protein. The MBP-AoACBP protein was purified by an amylose resin chromatography column. SDS-PAGE showed that MBP-AoACBP has an estimated molecular weight of 82 kDa. Microscale thermophoresis binding assay showed that the recombinant AoACBP displayed much greater affinity for palmitoyl-CoA (K d = 80 nM) than for myristoyl-CoA (K d = 510 nM), thus demonstrating the preference of AoACBP for long-chain acyl-CoA. CONCLUSION: The data support the identification of AoACBP as a long-chain ACBP in A. oryzae. PMID- 26677125 TI - Artificial Selection of Gn1a Plays an Important role in Improving Rice Yields Across Different Ecological Regions. AB - BACKGROUND: Rice is one of the most important crops, and it is essential to improve rice productivity to satisfy the future global food supply demands. Gn1a (OsCKX2), which encodes cytokinin oxidase/dehydrogenase, plays an important role in regulating rice grain yield. RESULTS: In this study, we analyzed the genetic variation of Gn1a, which influences grain yield through controlling the number of spikelets in rice. The allelic variations in the promoter, 5' untranslated region (UTR) and coding sequence (CDS) of Gn1a were investigated in 175 cultivars and 21 wild rice accessions. We found that Gn1a showed less sequence variation in the cultivars, but exhibited significant nucleotide diversity in wild rice. A total of 14 alleles, named AP1 to AP14, were identified in the cultivars based on the amino acid divergence of GN1A. Association analysis revealed that the number of spikelets and grain yield were significantly different between the different alleles. Phylogenetic analysis indicated that the three main alleles, AP3, AP8 and AP9, in the cultivars might originate from a common ancestor allele, AP1, in wild rice. CONCLUSIONS: Of these alleles in the cultivars, AP9 was suggested as the best allele in indica, as it has shown strong artificial selection in breeding high-yield rice in the past. It might be valuable to explore the high yield-related alleles of Gn1a to develop high-yield rice cultivars in future breeding programs. PMID- 26677126 TI - Participation in pediatric oncology: views of child and adolescent patients. AB - OBJECTIVE: The aim of the present study is to explore patient's perspectives in pediatric oncology on participation in discussions and decision-making surrounding their cancer diagnosis. METHODS: Seventeen patients between 9 and 17 years of age receiving treatment at centers of the Swiss Pediatric Oncology Group were interviewed for this study. Their interview data was analyzed qualitatively to identify themes with regard to participation in medical communication and/or decision-making. RESULTS: Participants highlighted how their roles in health care discussions varied from direct participation to indirect involvement. Overall, there were fewer accounts of involvement in decision-making than in overall health care discussions. Challenges with regard to completely understanding the information provided and making decisions were identified. Participants also discussed situations when they were not involved in medical communication or decision-making. While they generally valued their participation, the preferred level of involvement oscillated between participants as well as within one and the same child across time. CONCLUSIONS: The complex pattern of participation found in this study calls for a flexible model of involving children and adolescents in health care that accounts for the varying roles and preferences that they manifest. A patient may appreciate active involvement in some decisions while choosing to remain in the background for others. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26677127 TI - Cancellous and Cortical Bone Microarchitectures of Femoral Neck in Rheumatoid Arthritis and Osteoarthritis Compared with Donor Controls. AB - This study investigated the 3D microarchitecture of cancellous and cortical bones of the femoral neck in rheumatoid arthritis (RA), osteoarthritis (OA) and donor controls. 26 femoral necks (including heads) were harvested during total hip replacement surgeries in 11 patients with RA (mean age 66.7 +/- 12.8 years) and 15 patients with OA (67.3 +/- 8.4 years). Femoral heads/necks were also harvested from 8 donors (74.9 +/- 10.2 years). Bone samples of 10 mm thickness were prepared from each femoral neck and scanned with micro-CT to evaluate microarchitectural parameters. The RA and OA samples showed no significant differences in microarchitectural parameters in cancellous or cortical bone. Compared with the donor controls, bone volume fraction in RA and OA cancellous bone was significantly greater, the structure model index in OA was significantly lower, and the surface density in RA was significantly greater. The RA bone tissues showed erosion and marked osteophyte formation. This study demonstrated that RA and OA have similar trends of overall microarchitectural degeneration in the femoral neck, despite marked erosion in RA bone and osteophyte formation in OA bone. However, we could not eliminate the possibility of local differences between RA and OA bone. The age-related bone loss in RA and OA was less severe than those of normal ageing and osteoporosis, suggesting a compensatory effect of the diseases to increase bone density. PMID- 26677128 TI - Effective photocatalytic dechlorination of 2,4-dichlorophenol by a novel graphene encapsulated ZnO/Co3O4 core-shell hybrid under visible light. AB - In the present work, a graphene encapsulated ZnO/Co3O4 (GE/ZnO/Co3O4) core-shell hybrid is fabricated through a facile self-assembly approach, where the mutual electrostatic interaction force drives the ZnO/Co3O4 heteronanostructures to be fully wrapped with flexible ultrathin graphene shells. The as-prepared GE/ZnO/Co3O4 core-shell hybrid is characterized and exhibits excellent visible light photocatalytic ability toward dechlorination of 2,4-dichlorophenol (2,4 DCP) in the aqueous phase. It is worth noting that 2,4-DCP is almost completely mineralized into CO2 and H2O by the GE/ZnO/Co3O4 after 5 h of a photocatalytic reaction. This type of higher dechlorination and mineralization efficiency of 2,4 DCP is not generally observed, and is found to be higher than some previous studies. The dechlorination of 2,4-DCP has been achieved under different parametric conditions. The unique architecture of the GE/ZnO/Co3O4 core-shell hybrid also provides high stability and recyclability towards degradation of 2,4 DCP. The higher photocatalytic activity of the hybrid can be ascribed to the synergistic effect of ZnO, Co3O4 and graphene, and also by an increase in the contact surface between the metal oxide core and the graphene shell, which acts as a continuous path for rapid electron transport to offer a greater number of reactive species. PMID- 26677130 TI - Sonographic characteristics of pharyngoesophageal diverticula: Report of 14 cases and review of the literature. AB - PURPOSE: Our aim was to report the characteristics of pharyngoesophageal diverticula on sonographic (US) examination. METHODS: We retrospectively reviewed the medical records and images of 14 patients whose pharyngoesophageal diverticula had been found first on thyroid US. The diagnoses had been confirmed on barium-swallow esophagography. RESULTS: All nodules were located posterior to the left thyroid lobe, having a clear hypoechoic border with the thyroid. The maximal diameter ranged from 0.7 to 3.3 cm (mean, 1.3 cm). The appearances on US examination were variable according to the size and amount of air inside the sac. Three nodules less than 1 cm contained little air and were hypoechoic, with internal microbubbles mimicking microcalcifications. Four nodules of larger size contained little air and had inhomogeneous echogenicity with internal echogenic spots and lines without posterior shadowing. Seven nodules contained more air, and an arc-shaped hyperechoic line with a posterior reverberation artifact was observed within the sac. After the patients swallowed water, the shape and echogenicity of the nodules had changed, and on US, all nodules were seen to connect with the adjacent esophagus. Subsequent barium-swallow esophagography confirmed the diagnoses. CONCLUSIONS: An air-containing nodule located posterior to the left thyroid and connected to the cervical esophagus is indicative of a pharyngoesophageal diverticulum on US examination. Swallowing maneuvers are helpful in differentiating these diverticula from thyroid and parathyroid nodules. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:333-338, 2016. PMID- 26677131 TI - Well-Dispersed ZIF-Derived Co,N-Co-doped Carbon Nanoframes through Mesoporous Silica-Protected Calcination as Efficient Oxygen Reduction Electrocatalysts. AB - A well-dispersed Co,N co-doped carbon nanoframework (Co,N-CNF) with hierarchically porous structure is successfully synthesized from zeolitic imidazolate framework (ZIF) precursors via a mesoporous-silica-protected calcination strategy. By preventing the irreversible fusion and aggregation during the high-temperature pyrolysis step with this protection strategy, the Co,N-CNF exhibits comparable oxygen reduction reaction (ORR) catalytic activity to that of commercial Pt catalysts with the same loading. PMID- 26677129 TI - Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients. AB - HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression. PMID- 26677132 TI - Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins. AB - Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. PMID- 26677133 TI - Analysis of Online Ratings of Dermatologists. PMID- 26677134 TI - Selective and directional actuation of elastomer films using chained magnetic nanoparticles. AB - We report selective and directional actuation of elastomer films utilizing magnetic anisotropy introduced by chains of Fe3O4 magnetic nanoparticles (MNPs). Under uniform magnetic fields or field gradients, dipolar interactions between the MNPs favor magnetization along the chain direction and cause selective lifting. This mechanism is described using a simple model. PMID- 26677136 TI - WITHDRAWN: Arthroscopy for temporomandibular disorders. PMID- 26677135 TI - IL-17 intensifies IFN-gamma-induced NOS2 upregulation in RAW 264.7 cells by further activating STAT1 and NF-kappaB. AB - Interleukin-17 (IL-17) is a signature cytokine of Th17 cells. Previous research has indicated that IL-17 plays a proinflammatory role by exacerbating interferon gamma (IFN-gamma)-induced inflammation. However, prior to this study, it was not known whether inducible nitric oxide synthase (iNOS or NOS2), a signature molecule of inflammation, could be intensified by IL-17 when combined with IFN gamma. Thus, we explored the roles and underlying mechanisms of IL-17 and IFN gamma in the regulation of NOS2 expression in RAW 264.7 cells using qPCR, western blot analysis, colorimetric analysis, ChIP assay and statistical analysis. Although IL-17 alone did not induce NOS2 expression or nitric oxide (NO) production, as shown by western blot analysis and colorimetric analysis, it intensified IFN-gamma-induced NOS2 upregulation and NO production in RAW 264.7 cells. The alteration of relevant transcription factors demonstrated that a combination of IFN-gamma and IL-17 enhanced Tyr701-phosphorylated signal transducer and activator of transcription 1 [p-STAT1(Y701)] and nuclear factor kappaB (NF-kappaB) activation, nuclear translocations and their binding to the NOS2 promoter, compared with IFN-gamma alone, as illustrated by the results of the western blot analysis and ChIP assay. Also, using the corresponding inhibitors of STAT1 and NF-kappaB, we noted downregulation of the expression of NOS2 induced by IFN-gamma alone or in combination with IL-17, respectively. In addition, IFN-gamma increased phosphorylated (p-)p38 mitogen-activated protein kinase (MAPK), and accelerated the activation of the NF-kappaB pathway and the expression of NOS2, but phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was reduced by treatment with IFN-gamma and IL-17. IL-17 intensified the activation of the NF-kappaB pathway and NOS2 upregulation induced by IFN gamma by increasing the phosphorylation of p38 MAPK and limiting the phosphorylation of ERK1/2. Taken together, these results suggest that IL-17 intensified IFN-gamma-induced NOS2 upregulation and NO production by increasing the transcription activity of p-STAT1(Y701) and NF-kappaB in RAW 264.7 cells. Further activation of the NF-kappaB pathway induced by IL-17 relied on enhanced phosphorylation of p38 MAPK and decreased phosphorylation of ERK1/2. The mechanism suggested in this study provides novel information which may be used for anti-inflammatory therapy with IL-17. PMID- 26677137 TI - Combined bioelectrochemical-electrical model of a microbial fuel cell. AB - Several recent studies demonstrated significant charge storage in electrochemical biofilms. Aiming to evaluate the impact of charge storage on microbial fuel cell (MFC) performance, this work presents a combined bioelectrochemical-electrical (CBE) model of an MFC. In addition to charge storage, the CBE model is able to describe fast (ms) and slow (days) nonlinear dynamics of MFCs by merging mass and electron balances with equations describing an equivalent electrical circuit. Parameter estimation was performed using results of MFC operation with intermittent (pulse-width modulated) connection of the external resistance. The model was used to compare different methods of selecting external resistance during MFC operation under varying operating conditions. Owing to the relatively simple structure and fast numerical solution of the model, its application for both reactor design and real-time model-based process control applications are envisioned. PMID- 26677139 TI - Regulation of cyclic AMP response element-binding protein during neuroglial interactions. AB - Communications between neurons and glial cells play an important role in regulating homeostasis in the central nervous system. cAMP response element binding protein (CREB), a transcription factor, is down-regulated by neurotoxins, which are known to be released by activated glial cells. To determine the role of CREB signaling in neuroglial interactions, we used three neuroglial coculture models consisting of human neuroprogenitor cell (NPC)-derived neurons and human microglia. Conditioned medium from the Abeta (Abeta)-activated microglia decreased CREB phosphorylation and brain-derived neurotrophic factor promoter activity (47%), whereas the same medium induced (p < 0.01) the promoter of CXCL10, a chemokine, in NPC-derived neuron-rich cultures. These effects were reversed when microglia were exposed to Abeta in the presence of minocycline, an anti-inflammatory agent. The expression of CREB targets, including brain-derived neurotrophic factor, synapsin-1, and BIRC3 decreased by 50-65% (p < 0.01) in neurons isolated by laser capture microdissection in close proximity of microglia in neuroglial mixed cultures. Neuronal survival actively modulated microglial behavior when neurons and microglia were cocultured side-by-side on semicircles of ACLAR membrane. Neuronal injury, caused by the over-expression of dominant negative form of CREB, exacerbated Abeta-mediated microglial activation, whereas CREB over-expression resulted in decreased microglial activation. Decreases in the levels of neuronal markers were observed when NPCs were differentiated in the presence of proinflammatory cytokines IL-1beta, tumor necrosis factor alpha, or IL-6. Instead, the NPCs differentiated into a glial phenotype, and these effects were more pronounced in the presence of tumor necrosis factor alpha. Our findings suggest that CREB down-regulation is an important component of defective neuroglial communications in the brain during neuroinflammation. Neuroglial interactions were examined using coculture models of human neuroprogenitor cell derived neurons and microglia isolated from human fetal brain. A novel coculture model of neurons and microglia cultured on ACLAR membranes in the same dish was also included. In this model, over-expression of the dominant negative mutant form of the transcription factor CREB in neurons induced neuronal apoptosis and microglial activation whereas expression of the wild type form of CREB resulted in protection of neurons and suppressed microglial activity, thereby suggesting that neurons play an active role in neuroglial interactions. PMID- 26677138 TI - Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection. AB - Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury. PMID- 26677140 TI - Correlation between oxidative stress and the NF-kappaB signaling pathway in the pulmonary tissues of obese asthmatic mice. AB - The obesity-asthma phenotype is characterized by increased asthma severity and decreased glucocorticoid responsiveness. To date, the mechanism underlying the association between obesity and asthma remain to be fully elucidated. The present study investigated the correlation between oxidative stress and the nuclear factor (NF)-kappaB pathway in obese asthmatic mice. The animals were divided into the following groups: Control (n=8), comprising C57BL/6J mice without exposure to a high-fat diet; non-obese asthma group (n=8), comprising mice of a normal weight subjected to the induction of asthma; obese control group (n=8), comprising C57BL/6J mice subjected to a high-fat diet; and obese asthmatic group (n=8), comprising obese mice subject to the induction of asthma. The levels of the malondialdehyde (MDA) oxidant and glutathione (GSH) antioxidant in the lungs and bronchoalveolar lavage fluid (BALF) were measured using ELISA. The expression levels of inhibitory kappaB kinase-beta (IKK-beta) and the inhibitor of kappaBalpha (IkappaB-alpha) in the pulmonary tissues was determined using western blot analysis. An electrophoretic mobility shift assay was performed to determine the transcription activity of NF-kappaB. The levels of MDA in the BALF and lung tissues increased significantly in the two asthmatic groups, compared with the control groups (P<0.01). The asthmatic mice showed significantly lower concentrations of GSH in the BALF and lung tissues, compared with the control groups (P<0.01). In the asthmatic animals, the expression of IkappaB kinase (IKK) beta and activation of NF-kappaB were upregulated in the pulmonary tissues, compared with those in the control groups (P<0.01). The expression of IKK-beta and transcriptional activity of NF-kappaB were significantly higher the in obese asthmatic mice, compared with the non-obese asthmatic mice (P<0.01). On examining the expression levels of IkappaB-alpha in the pulmonary tissues, a significant reduction was found in the asthmatic animals, compared with the controls (P<0.01). In addition, the level of IkappaB-alpha was significantly lower in the obese asthmatics, compared with the non-obese asthmatics (P<0.01). MDA was positively correlated with NF-kappaB in the obese asthmatic group (R=0.83; P<0.05) and non-obese asthmatic group (R=0.82; P<0.05). Oxidative stress was upregulated in the pulmonary tissues of the asthmatic mice. This upregulation was more marked in the obese asthmatic mice, and was positively correlated with activation of the NF-kappaB signaling pathway in the pulmonary tissues. The results in the present study indicated that higher oxidative stress and activation of the NF-kappaB signaling pathway were observed in the lung tissues of the obese asthmatics. Furthermore, a positive correlation was identified between oxidative stress and NF-kappaB. PMID- 26677141 TI - Synergistic dual-pH responsive copolymer micelles for pH-dependent drug release. AB - The tuning of the structure of nanocarriers with fast acidic-degradation rate and high stability in physiological conditions or during storage is under intensive study. In this context, a kind of dual-pH responsive micelles with well-balanced stability, that is, fast hydrolysis in acidic environment and stability towards blood drug release at 7.4 were developed. This is achieved by the self-assembly of micelles of poly(ethylene glycol)-b-(poly epsilon-caprolactone-g-poly(2,2 dimethyl-1,3-dioxolane-4-yl)methylacrylate-co-2(dimethylamino)ethyl methacrylate) (mPEG-b-(PCL-g-P(DA-co-DMAEMA))) copolymers with two inert pH responsive moieties of DA and DMAEMA. The fast synergistic acid-triggered disassembly and high stability at physiological condition of the mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles was verified by (1)H NMR, particle size and optical stability measurements, which was induced and mediated by the synergistic pH responses of the hydrolysis of the ketal in DA moieties and the switch in solubility of tertiary amino moieties (DMAEMA) under mild acid conditions. It was observed that the hydrolysis rate of the ketal could be promoted by increasing the content of DMAEMA moieties. The fast intracellular disassembly of the micelles depending on the contents of DMAEMA moieties was also traced by fluorescence resonance energy transfer (FRET). The in vitro release studies showed that the release of DOX from mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles at mild acid condition was significantly accelerated by increasing the content of DMAEMA moieties, while greatly impeding drug release in physiological conditions. The antitumor activity of DOX-loaded micelles was studied in MCF-7 and 4T1 cells in vitro and in 4T1 tumor-bearing Balb-c mice in vivo. The results indicated the DOX-loaded micelles with higher content of DMAEMA moieties exhibited enhanced anticancer activity. Collectively, the synergistic dual-pH responsive design of mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles provided a new route for improving anticancer drug delivery efficiency. PMID- 26677142 TI - Photocaged Arabinose: A Novel Optogenetic Switch for Rapid and Gradual Control of Microbial Gene Expression. AB - Controlling cellular functions by light allows simple triggering of biological processes in a non-invasive fashion with high spatiotemporal resolution. In this context, light-regulated gene expression has enormous potential for achieving optogenetic control over almost any cellular process. Here, we report on two novel one-step cleavable photocaged arabinose compounds, which were applied as light-sensitive inducers of transcription in bacteria. Exposure of caged arabinose to UV-A light resulted in rapid activation of protein production, as demonstrated for GFP and the complete violacein biosynthetic pathway. Moreover, single-cell analysis revealed that intrinsic heterogeneity of arabinose-mediated induction of gene expression was overcome when using photocaged arabinose. We have thus established a novel phototrigger for synthetic bio(techno)logy applications that enables precise and homogeneous control of bacterial target gene expression. PMID- 26677143 TI - Metal-mediated climate susceptibility in a warming world: Larval and latent effects on a model amphibian. AB - Although sophisticated models predict the effects of future temperatures on ectotherms, few also address how ubiquitous sublethal contaminants alter an organism's response to thermal stress. In ectotherms, higher metabolic rates from warming temperatures can beneficially speed metabolism and development. If compounded by chronic, sublethal pollution, additional resource demands for elimination or detoxification may limit their ability to cope with rising temperatures-the toxicant-induced climate susceptibility hypothesis. In outdoor bioassays, using natural lake water as the background, the authors investigated the development of a model ectotherm in 6 levels of Cd, Cu, and Pb mixtures and 3 thermal regimes of diel temperature fluctuations: ambient, +1.5 degrees C, and +2.5 degrees C. Warming had no effect on wild-caught Cope's gray tree frog (Hyla chrysoscelis) until metals concentrations were approximately 10-fold of their bioavailable chronic criterion unit (sums of bioavailable fractions of chronic criteria concentrations). In treatments with >=10 bioavailable chronic criterion units and +1.5 degrees C, growth increased. Conversely, in treatments with 28 bioavailable chronic criterion units and maximal +2.5 degrees C warming, growth declined and the body condition of postmetamorphic juveniles at 20 d was 34% lower than that of juveniles from background conditions (lake water at ambient temperatures). These findings suggest toxicant-induced climate susceptibility with long-term latent effects on the juvenile life stage. Sublethal contaminants can intensify the impact on aquatic ectotherms at the most conservative levels of predicted global warming over the next century. Environ Toxicol Chem 2016;35:1872 1882. (c) 2015 SETAC. PMID- 26677144 TI - Cinnamaldehyde affects the biological behavior of human colorectal cancer cells and induces apoptosis via inhibition of the PI3K/Akt signaling pathway. AB - Cinnamaldehyde (CA) is a bioactive compound isolated from the stem bark of Cinnamomum cassia, that has been identified as an antiproliferative substance with pro-apoptotic effects on various cancer cell lines in vitro. In the present study, the effects of CA on human colon cancer cells were investigated at both the molecular and cellular levels. Three types of colorectal cancer cells at various stages of differentiation and invasive ability (SW480, HCT116 and LoVo) were treated with CA at final concentrations of 20, 40 and 80 ug/ml for 24 h. Compared with the control group, the proliferation inhibition rate of the human colorectal cancer cells following treatment with CA increased in a dose- and time dependent manner. The invasion and adhesion abilities of the cells were significantly inhibited as indicated by Transwell and cell-matrix adhesion assays. Meanwhile, CA also upregulated the expression of E-cadherin and downregulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. CA also elevated the apoptotic rate. The levels of pro-apoptotic genes were upregulated while the levels of apoptosis inhibitory genes were decreased which further confirmed the pro-apoptotic effect of CA. In order to explore the mechanism of CA-induced apoptosis, insulin-like growth factor-1 (IGF-1) and PI3K inhibitor (LY294002) were used to regulate the phosphoinositide 3-kinase (PI3K)/AKT pathway. The transcription activity of PI3K/AKT was markedly inhibited by CA, as well as IGF-1 which functions as an anti-apoptotic factor. In conclusion, CA has the potential to be developed as a new antitumor drug. The mechanisms of action involve the regulation of expression of genes involved in apoptosis, invasion and adhesion via inhibition of the PI3K/Akt signaling pathway. PMID- 26677145 TI - Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation. AB - The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation. PMID- 26677146 TI - The impact of medication-focused workshops in a diabetes educational program in jail: a pilot study. AB - BACKGROUND: Correctional institutions have unique circumstances offering care and the opportunity to adopt healthy behaviours for populations suffering from chronic diseases such as diabetes. In view of their expertise on medication, pharmacists can contribute to multidisciplinary educational health programmes in prisons. OBJECTIVE: To assess the effectiveness of a pharmacist led diabetes medication-related workshops. METHOD: Pharmacists led workshops about patients' empowerment in their treatment within the educational program. On a prospective observational study basis, the impact was assessed in terms of relevance, learning outcomes and achievement transfer using the Kirkpatrick training assessment method. Hb1Ac was measured as glycemic control outcome. RESULTS: Fifteen patients involved in the workshops showed a significant decrease in HbA1c compared to the control group (-1.18 +/- 0.52 vs. +0.26 +/- 0.28 %; p < 0.001). RELEVANCE: All participants were satisfied and ready to join other sessions. LEARNING OUTCOMES: (LO) Postworkshop scores were significantly improved (LO1: 4.2 +/- 0.9 vs. 2.2 +/- 1.4; LO2: 4.5 +/- 0.9 vs. 2.6 +/- 1.3; p < 0.05). Decrease in HbA1c was correlated to increase in LO2's scores. (Y = 0.946 - 1.134X; R = 0.692; p < 0.05). ACHIEVEMENT TRANSFER: Key points from all LOs were reported. In case studies, 70 % of participants adopted healthy strategies (LO3). CONCLUSION: These results highlight the positive impact of the workshops and the additive value of pharmacists' involvement within the educational program in jail. PMID- 26677147 TI - Haemophilia A in a major trauma patient. AB - Haemophilia A is a coagulopathy with an absence or functional deficiency of coagulation factor VIII. The disease can be subdivided into a congenital form (incidence 1:10,000-1:20,000) and an acquired form (incidence 1:1,000,000). Both forms present an increased risk of bleeding even in low-impact trauma in severe cases of haemophilia A. The course of a man with haemorrhagic shock after a fall from a height of more than 3 m is described. After the secondary survey in the intensive care unit, several interventions (laparotomy, mass transfusion) were performed to stop the bleeding. A history of haemophilia was belatedly reported by relatives. The activity of factor VIII was determined, and substitution was initiated. No recurrent signs of bleeding occurred. The patient survived in good condition and presented for follow-up 3 years later with no disabilities. PMID- 26677148 TI - Serum sickness-like reaction after influenza vaccination. AB - Serum sickness (SS) and SS-like reaction (SSLR) are rare immune complex-mediated hypersensitivity illnesses characterised by key features of fever, rash, polyarthralgia or polyarthritis. They are self-limiting with an excellent prognosis, settling as the antigen is cleared. We describe a 30-year-old man who presented with fever, rash, polyarthralgia and subcutaneous soft tissue swelling in his hands and feet at day 5 after influenza vaccination. A thorough investigation for infective and autoimmune causes for the presenting symptoms was negative. Given the temporal relationship between the symptoms and influenza vaccination, clinical evidence and biological plausibility of influenza vaccination causing SSLR, a clinical diagnosis of SSLR was made. The patient was treated with anti-histamines, non-steroidal anti-inflammatories and glucocorticoids with gradual resolution of symptoms over 5 weeks. PMID- 26677149 TI - Mystery of a cryptogenic stroke solved by an abdominal angiogram. AB - Despite advances in the field of imaging and diagnostics, the incidence of cryptogenic stroke is still around 30-40% in modern stroke databases. Our patient presented with recurrent midbrain infarcts over 3 years and was initially labelled as a patient with cryptogenic stroke. His blood investigations were normal, work up for autoimmune disorders was negative, CT brain angiogram was normal and a two-dimensional echo showed a small patent foramen ovale with a left to right shunt. He later presented with a right perinephric haematoma and an abdominal angiogram revealed multiple microaneurysms of the renal arteries, coeliac trunk and the mesenteric arterial system. The feeding renal artery was embolised. A diagnosis of polyarteritis nodosa was made. The patient was subjected to digital subtraction angiography of neck and intracranial vessels, which revealed multiple microaneurysms in internal and external carotid artery territory. He was discharged with steroids and azathioprine. PMID- 26677150 TI - Lung carcinoma presenting as a solitary, painless frontal bone lump. AB - A 50-year-old patient, a smoker, was admitted to the hospital, with a solitary scalp lump. Subcutaneous lumps of the scalp are common but usually benign; however, the painless lump in our patient turned out to be a malignant osteolytic lesion of the skull. Frontal bone was involved, and the disease had spread to the dura. Neuroimaging showed osteolytic lesions involving the axial skeleton, skull and several vertebrae. MRI showed the involvement of the second cervical vertebra, which prompted us to start treatment with dexamethasone. Since the spinal cord was not involved, Oncologists decided not to start radiotherapy treatment until we had reached the final diagnosis. A frontal bone biopsy confirmed the diagnosis of lung carcinoma. Chest X-ray did not identify the pulmonary nodule, but CT scan revealed a 1 cm peripheral, spiculated, pulmonary nodule within a pathological parenchyma (severe diffuse pulmonary emphysema). PMID- 26677151 TI - Tumefactive demyelination presenting during bevacizumab treatment. AB - We report the emergence of tumefactive demyelination during treatment with intravitreal bevacizumab (Avastin). This is of particular significance given that bevacizumab is currently being assessed as a potential treatment option for neuromyelitis optica, another demyelinating condition. PMID- 26677152 TI - Right ventricular failure due to late embolic RV infarction during continuous flow LVAD support. AB - This report describes a 63-year-old man with a dilated cardiomyopathy, who was supported with a continuous flow left ventricular assist device (LVAD), and on the waiting list for heart transplantation. After a long period of stability, he presented with recurrent ventricular tachycardia and rapidly developed progressive right ventricular (RV) failure. He required implantation of a temporary RV assist device to regain stability and subsequently underwent urgent heart transplantation. The explanted heart showed multiple areas of ischaemic damage to the RV myocardium, but there was no significant underlying coronary artery disease. It appears that the ventricular arrhythmias and subsequent RV failure were due to an embolic event in the territory of the right coronary artery. The case highlights that coronary embolism is a rare cause of RV failure during LVAD support and demonstrates the utility of temporary RV assist device support as a bridge to heart transplantation. PMID- 26677153 TI - Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient. AB - A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature. PMID- 26677154 TI - Definitive use of external fixation for pelvic ring injuries (open book/APC2) in pregnancy. AB - Pelvic fractures in pregnancy are rare, resulting in a paucity of evidence-based management. We describe a case of open book pelvic injury in a 32-year-old woman in her third trimester of pregnancy. She was successfully managed with a supra acetabular external fixator, which allowed the safe delivery of a healthy baby boy at 34 weeks, via caesarean section. The external fixator was removed postpartum, when the pelvis was deemed stable, and mother and baby both continue to do well. This is the only case in the literature that demonstrates the successful use of external fixation for pelvic injuries in pregnancy. PMID- 26677155 TI - Spots of bother. PMID- 26677156 TI - Bilateral closed flexor pollicis longus musculotendinous junction ruptures. AB - We present a case of bilateral closed flexor pollicis longus musculotendinous junction ruptures. Our case suggests multifactorial aetiology and provides further evidence for genetic influences in musculotendinous junction injuries. PMID- 26677157 TI - Double aortic arch: a cause of stridor to remember. PMID- 26677158 TI - Anterior surface opacification of intraocular lenses after Descemet's stripping automated endothelial keratoplasty. AB - Descemet's stripping automated endothelial keratoplasty (DSAEK) is today recognised as the surgical procedure of choice for corneal endothelial dysfunction. The triple procedure (either staged or combined), whereby cataract surgery can be performed at the same time as endothelial keratoplasty, is well suited for patients with Fuch's endothelial dystrophy with decreased vision due to endothelial guttata, early stromal oedema and cataract formation. Recognised complications of DSAEK include donor graft detachment/dislocation, primary graft failure and pupillary block by air. Intraocular lens (IOL) opacification is a complication that is becoming apparent in patients who have undergone DSAEK and, to date, no definitive mechanism of such opacification has been discovered. Primary postoperative optic opacification of hydrophilic acrylic IOL designs has been attributed to the formation of calcium phosphate deposits. This has led to changes in lens designs, manufacturing processes and packaging. Secondary calcification is thought to be caused by environmental factors unrelated to the IOL model, such as breakdown of the blood-aqueous barrier. In this report, four cases of IOL anterior surface opacification are described in patients who required both cataract surgery and DSAEK. Only one case had cataract surgery and DSAEK performed concurrently, with the remainder having DSAEK performed at variable timeframes after cataract surgery. PMID- 26677159 TI - Juvenile spondyloarthropathy: an important clinical lesson to remember. AB - Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted. PMID- 26677160 TI - Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy. AB - Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse. PMID- 26677161 TI - A rare cause of recurrent wheeze and seizures. AB - A 34-year-old woman presented with recurrent attacks of breathlessness and seizures. The patient's condition worsened during the course of her hospital stay, as a result of which she had to be intubated twice. Radiological studies showed a mass in the trachea and the subsequent biopsy of the mass revealed an infiltrating carcinoma with morphological features of adenoid cystic carcinoma. PMID- 26677162 TI - Using occupancy modelling to compare environmental DNA to traditional field methods for regional-scale monitoring of an endangered aquatic species. AB - Environmental DNA (eDNA) monitoring approaches promise to greatly improve detection of rare, endangered and invasive species in comparison with traditional field approaches. Herein, eDNA approaches and traditional seining methods were applied at 29 research locations to compare method-specific estimates of detection and occupancy probabilities for endangered tidewater goby (Eucyclogobius newberryi). At each location, multiple paired seine hauls and water samples for eDNA analysis were taken, ranging from two to 23 samples per site, depending upon habitat size. Analysis using a multimethod occupancy modelling framework indicated that the probability of detection using eDNA was nearly double (0.74) the rate of detection for seining (0.39). The higher detection rates afforded by eDNA allowed determination of tidewater goby occupancy at two locations where they have not been previously detected and at one location considered to be locally extirpated. Additionally, eDNA concentration was positively related to tidewater goby catch per unit effort, suggesting eDNA could potentially be used as a proxy for local tidewater goby abundance. Compared to traditional field sampling, eDNA provided improved occupancy parameter estimates and can be applied to increase management efficiency across a broad spatial range and within a diversity of habitats. PMID- 26677163 TI - Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection. AB - This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(*))/alpha-tocopherol (alpha-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(*))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-kappaB (NF-kappaB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID- 26677164 TI - Transitions in the Prophylaxis, Treatment and Care of Patients with Venous Thromboembolism. AB - INTRODUCTION: Patients experience numerous transitions, including changes in clinical status, pharmacologic treatment and prophylaxis, and progression through the physical locations of their healthcare setting as they advance through a venous thromboembolism (VTE) clinical experience. This review provides an overview of these transitions and highlights how they can impact clinical care. METHODS: Major public resources (PubMed, MEDLINE, and Google Scholar) were searched using various combinations of the terms: "venous thromboembolism", "deep vein thromboses", "pulmonary embolism", "transitions in care", and "hospital protocols" to identify narrative reviews, professional guidelines, or primary manuscripts reporting protocol development strategies and/or clinical data, published in English from 2010 through January 2015. The studies included in this review were selected on the basis of extensive reading of the literature and the author's clinical expertise. RESULTS: VTE treatment and prophylaxis is a dynamic process requiring ongoing patient assessments and adjustments to therapeutic strategies as the patient progresses through various hospital and outpatient settings. Throughout these transitions in care, physicians need to be vigilant of any changes in the patient's clinical condition which may impact the patient's risk of VTE, and re-evaluate the intervention(s) employed when such changes occur. A standardized, interdisciplinary VTE clinical pathway developed for medical patients with acute VTE resulted in decreased utilization of hospital resources and healthcare costs, suggesting that further research is warranted in this area. CONCLUSION: The prevention and management of VTE can be optimized by the development and local implementation of standardized evidence-based clinical pathways. PMID- 26677165 TI - Assessment of the Quantitative Value Usefulness of the Aldosterone-Renin Ratio (ARR) for Primary Aldosteronism (AQUARR) Study. AB - Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism (PA), the most common cause of secondary hypertension, in selected hypertensive patients. "Confirmatory" tests are then recommended in patients who tested positive at the ARR to exclude from further diagnostic work-up false positive results. Based on our experience we hypothesized that the ARR carries quantitative information, which can avoid the need of confirmatory tests. We herein describe a study protocol to identify the ARR cut-off value with a high specificity for the exclusion of aldosterone producing adenoma (APA) based on analysis of two large prospectively collected datasets of patients in which a conclusive diagnosis of APA was made by the four corners criteria. This will also serve to investigate the diagnostic gain provided over this ARR cut-off value by one confirmatory test, the captopril challenge test. Hence, with this protocol we expect to identify an ARR cut-off value that might prevent further testing in patients with either a low or a high probability of APA. This could translate in a higher diagnostic accuracy and, by preventing unnecessary invasive testing, into a substantial saving of money, time, and resources. PMID- 26677166 TI - Sulphide Resistance in the Cyanobacterium Microcystis aeruginosa: a Comparative Study of Morphology and Photosynthetic Performance Between the Sulphide-Resistant Mutant and the Wild-Type Strain. AB - The cyanobacterium Microcystis aeruginosa is a mesophilic freshwater organism, which cannot tolerate sulphide. However, it was possible to isolate a sulphide resistant (S(r)) mutant strain that was able to survive in a normally lethal medium sulphide. In order to evaluate the cost of the mutation conferring sulphide resistance in the S(r) strain of M. aeruginosa, the morphology and the photosynthetic performance were compared to that found in the wild-type, sulphide sensitive (S(s)) strain. An increase in size and a disrupted morphology was observed in S(r) cells in comparison to the S(s) counterpart. Phycoerythrin and phycocyanin levels were higher in the S(r) than in the S(s) cells, whereas a higher carotenoid content, per unit volume, was found in the S(s) strain. The irradiance-saturated photosynthetic oxygen-production rate (GPR max) and the photosynthetic efficiency (measured both by oxygen production and fluorescence, alpha(GPR) and alpha(ETR)) were lower in the S(r) strain than in the wild-type. These results appear to be the result of package effect. On the other hand, the S(r) strain showed higher quantum yield of non-photochemical quenching, especially those regulated mechanisms (estimated throughout qN and Y(NPQ)) and a significantly lower slope in the maximum quantum yield of light-adapted samples (Fv'/Fm') compared to the S(s) strain. These findings point to a change in the regulation of the quenching of the transition states (qT) in the S(r) strain which may be generated by a change in the distribution of thylakoidal membranes, which somehow could protect metalloenzymes of the electron transport chain from the lethal effect of sulphide. PMID- 26677167 TI - A SURVEY OF RADIOLOGISTS AND REFERRING VETERINARIANS REGARDING IMAGING REPORTS. AB - An imaging report is a vital communication tool between a radiologist and clinician. In a field where in-person communication may not be readily available, it is imperative that the report clearly relays pertinent clinical information in a timely manner. The purpose of this observational study was to describe and compare opinions and expectations of small animal general practitioners, veterinary specialists, and veterinary radiologists regarding the imaging report. Online surveys were distributed, and data were collected from 202 veterinary clinicians and 123 veterinary radiologists. The majority (89%) of clinicians were satisfied with their imaging reports and stated that they read the radiology report as soon as it was available (92%). Just less than half (48%) of clinicians indicated it was standard of care that a board-certified veterinary radiologist read all imaging studies. Radiologists and clinicians agreed that a clinical history (98% and 94%, respectively) and clinical question (82% and 68%, respectively) were needed to generate a good radiology report. Fifty-five percent to 70% of clinicians prefer red bulleted reports, which included incidental findings (96%); while radiologists slightly favored prose reporting (37-46%). Clinicians found it helpful when additional imaging (86%), medical (71%), and surgical recommendations (73%) were made. About one-third of specialists who had been in practice for >11 years thought they were better able to interpret imaging for their own specialty than the radiologist. Clinicians voiced discontentment with reports that were not completed in a timely manner or did not give a prioritized differential list. Further studies are warranted to provide a more in depth evaluation of veterinary radiology reporting structure and style. PMID- 26677168 TI - Anion- and Solvent-Induced Assembly and Reversible Structural Transformation of d(10)-Metal Coordination Architectures Containing N-(4-(4 Aminophenyloxy)phenyl)isonicotinamide. AB - We set out studies on anion- and solvent-induced assembly based on the ligand N (4-(4-aminophenyloxy)phenyl)isonicotinamide (papoa), which is synthesized to show a bent and flexible backbone. Reactions of papoa with ZnX2 (X=Cl, Br, and I) gave the dinuclear macrocycles ([ZnX2 (papoa)]2 ; X=Cl (1 a), Br (2 a), I (3)), the structure of which was determined by X-ray diffraction. Notably, the less bulky Cl and Br compounds afforded the coordinated imine in acetone (i.e., [ZnX2 (papoi)]2 , papoi=N-(4-(4-(propan-2-ylideneamino)phenoxy)phenyl)isonicotinamide; X=Cl (1 b), Br (2 b)), whereas the iodine one only gave the coordinated amine compound 3 under the same reaction condition. In fact, the coordinated imine can return to the amine analogue upon exposure to air or in DMSO, which has been monitored by (1)H NMR spectroscopy and powder X-ray diffraction. Both the dinuclear [Zn(papoa)(NO3)2]2 (4 a) and the 1D [Zn(papoa)2(NO3)2]n (4 b) were formed from the reaction of Zn(NO3)2 and papoa in mixed solvents with acetone and acetonitrile, respectively. In addition, Cd(ClO4)2 can react with papoa to give the 1D framework {[Cd(papoa)2 (CH3CN)2](ClO4)2}n (5 a) and the 2D framework [Cd(papoa)2 (ClO4)2]n (5 b), depending on the solvent used, that is, MeOH and CH3CN, respectively. Importantly, the 1D framework with axially coordinated CH3 CN molecules and the 2D framework with axially coordinated ClO4(-) ions can be interconverted by heating and grinding in the presence of CH3CN, respectively. Such a reversible structural transformation process was proven by PXRD studies. PMID- 26677169 TI - Spontaneous uterine cornual rupture at 26 weeks' gestation in an interstitial heterotopic pregnancy following in vitro fertilization. AB - Interstitial implantation in a heterotopic pregnancy is extremely rare, and despite currently available diagnostic modalities, early identification of an interstitial ectopic pregnancy remains difficult. This report describes a case of spontaneous cornual rupture at 26 weeks' gestation in a woman with diamniotic dichorionic twins that resulted in live births. The patient had previously undergone laparoscopic bilateral salpingectomy, and the pregnancy was conceived with in vitro fertilization. Interstitial implantation in a heterotopic pregnancy can go unrecognized, resulting in increased maternal and infant morbidity and mortality. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:322-325, 2016. PMID- 26677170 TI - Dynamics and allostery of the ionotropic glutamate receptors and the ligand binding domain. AB - The dynamics of the ligand-binding domain (LBD) and the intact ionotropic glutamate receptor (iGluR) were studied using Gaussian Network Model (GNM) analysis. The dynamics of LBDs with various allosteric modulators is compared using a novel method of multiple alignment of GNM modes of motion. The analysis reveals that allosteric effectors change the dynamics of amino acids at the upper lobe interface of the LBD dimer as well as at the hinge region between the upper- and lower- lobes. For the intact glutamate receptor the analysis show that the clamshell-like movement of the LBD upper and lower lobes is coupled to the bending of the trans-membrane domain (TMD) helices which may open the channel pore. The results offer a new insight on the mechanism of action of allosteric modulators on the iGluR and support the notion of TMD helices bending as a possible mechanism for channel opening. In addition, the study validates the methodology of multiple GNM modes alignment as a useful tool to study allosteric effect and its relation to proteins dynamics. PMID- 26677172 TI - WITHDRAWN: Arthrocentesis and lavage for treating temporomandibular joint disorders. PMID- 26677171 TI - Tumour endothelial marker-8 in wound healing and its impact on the proliferation and migration of keratinocytes. AB - Chronic wound management represents a significant burden on healthcare systems and negatively impacts on the quality of patient life. New strategies to understand and identify wounds that will not heal in a normal manner are required. Tumour endothelial marker-8 (TEM-8) has been implicated in the wound healing and angiogenesis processes. TEM-8 expression was examined at the transcript level in a cohort of acute (n=10) and chronic (n=14) wounds and in normal skin (n=10). Protein analysis of TEM-8 was also undertaken for this cohort using immunohistochemistry (IHC). TEM-8 impact on keratinocyte cell growth and migration was assessed following TEM-8 ribozyme transgene transfection of human HaCaT keratinocytes using cell growth and electric cell-substrate impedance sensing (ECIS)-based assays. Expression of TEM-8 was observed to be increased in acute wounds compared to chronic wounds and normal skin using quantitative polymerase chain reaction transcript analysis and IHC staining of wound tissues. Knockdown of TEM-8 in HaCaT cells, using two independent ribozyme transgenes, resulted in significant decreases in cell growth as well as reductions in the rate of migration assessed using an ECIS-based system. TEM-8 may be differentially expressed between wound types and loss of this molecule impacts HaCaT growth and migration, potentially implicating this molecule as a factor involved in successful progression of wound healing. PMID- 26677173 TI - Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats. AB - It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase (MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug (AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38MAPK could participate in drug resistance in refractory epilepsy through the regulation of P gp. We show that the specific inhibitor of p38MAPK could down-regulate the expression of multidrug transporter (P-glycoprotein) in blood-brain barrier, increase the concentration of antiepileptic drugs in the hippocampal extracellular fluid and reduce anti-epileptic drug resistance in refractory epileptic rats. We propose that the p38MAPK signaling pathway participates in drug resistance in refractory epilepsy through the regulation of P-glycoprotein expression. PMID- 26677174 TI - Tissue kallikrein promotes survival and beta-catenin degradation in SH-SY5Y cells under nutrient stress conditions via autophagy. AB - Previous studies by our group showed that tissue kallikrein (TK) exerts neuroprotective effects during cerebral ischemia. Autophagy is an important adaptive response to cellular stress during nutrient deprivation, and beta catenin in known to repress autophagy. The present study investigated the possible involvement of autophagy and beta-catenin signaling in the protective effects of TK under nutrient deprivation-induced stress conditions. TK was shown to promote the survival and inhibit the death of SH-SY5Y cells under serum starvation and enhanced autophagic activity in a concentration-dependent manner, as indicated by augmented light chain (LC)3-II levels and Beclin-1 expression. The autophagy inhibitors 3-methyladenine and NH4Cl abolished the protective effects of TK. Of note, although serum starvation alone and TK treatment increased p62 protein levels and mRNA expression, incubation with the lysosome inhibitor NH4Cl increased the accumulation of LC3-II and p62 protein, indicating normal autophagic flux. It was also observed that beta-catenin expression was significantly downregulated by TK treatment. TK stimulated the interaction between LC3 and beta-catenin, and NH4Cl abolished the effects of TK on beta catenin levels in serum-starved cells, suggesting the autophagic degradation of beta-catenin, which may have led to the enhancement of autophagy. In conclusion, the findings of the present study demonstrated that TK promoted cell survival and beta-catenin degradation in serum-starved SH-SY5Y cells via increasing autophagy, which indicated the therapeutic potential of TK under nutrient deprivation associated stress conditions. PMID- 26677175 TI - A Comprehensive Study of Osteogenic Calcium Phosphate Silicate Cement: Material Characterization and In Vitro/In Vivo Testing. AB - Vertebral compression fractures can be successfully restored by injectable bone cements. Here the as-yet unexplored in vitro cytotoxicity, in vivo biodegradation, and osteoconductivity of a new calcium phosphate silicate cements (CPSC) are studied, where monocalcium phosphate (MCP; 5, 10, and 15 wt%) is added to calcium silicate cement (CSC). Setting rate and compressive strength of CPSC decrease with the addition of MCP. The crystallinity, microstructure, and porosity of hardened CPSC are evaluated by X-ray diffractometer, Fourier transform infrared spectroscopy, and microcomputed tomography (CT). It is found that MCP reacts with calcium hydroxide, one of CSC hydration products, to precipitate apatite. While the reaction accelerates the hydration of CSC, the formation of calcium silicate hydrate gel is disturbed and highly porous microstructures form, resulting in weaker compressive strength. In vitro studies demonstrate that CPSC is noncytotoxic to osteoblast cells and promotes their proliferation. In the rabbit tibia implantation model, clinical X-ray and CT scans demonstrate that CPSC biodegrades slower and osseointegrates better than clinically used calcium phosphate cement (CPC). Histological studies demonstrate that CPSC is osteoconductive and induces higher bone formation than CPC, a finding that might warrant future clinical studies. PMID- 26677176 TI - Systems Medicine: Sketching the Landscape. AB - To understand the meaning of the term Systems Medicine and to distinguish it from seemingly related other expressions currently in use, such as precision, personalized, -omics, or big data medicine, its underlying history and development into present time needs to be highlighted. Having this development in mind, it becomes evident that Systems Medicine is a genuine concept as well as a novel way of tackling the manifold complexity that occurs in nowadays clinical medicine-and not just a rebranding of what has previously been done in the past. So looking back it seems clear to many in the field that Systems Medicine has its origin in an integrative method to unravel biocomplexity, namely, Systems Biology. Here scientist by now gained useful experience that is on the verge toward implementation in clinical research and practice.Systems Medicine and Systems Biology have the same underlying theoretical principle in systems-based thinking-a methodology to understand complexity that can be traced back to ancient Greece. During the last decade, however, and due to a rapid methodological development in the life sciences and computing/IT technologies, Systems Biology has evolved from a scientific concept into an independent discipline most competent to tackle key questions of biocomplexity-with the potential to transform medicine and how it will be practiced in the future. To understand this process in more detail, the following section will thus give a short summary of the foundation of systems-based thinking and the different developmental stages including systems theory, the development of modern Systems Biology, and its transition into clinical practice. These are the components to pave the way toward Systems Medicine. PMID- 26677177 TI - Taking Bioinformatics to Systems Medicine. AB - Systems medicine promotes a range of approaches and strategies to study human health and disease at a systems level with the aim of improving the overall well being of (healthy) individuals, and preventing, diagnosing, or curing disease. In this chapter we discuss how bioinformatics critically contributes to systems medicine. First, we explain the role of bioinformatics in the management and analysis of data. In particular we show the importance of publicly available biological and clinical repositories to support systems medicine studies. Second, we discuss how the integration and analysis of multiple types of omics data through integrative bioinformatics may facilitate the determination of more predictive and robust disease signatures, lead to a better understanding of (patho)physiological molecular mechanisms, and facilitate personalized medicine. Third, we focus on network analysis and discuss how gene networks can be constructed from omics data and how these networks can be decomposed into smaller modules. We discuss how the resulting modules can be used to generate experimentally testable hypotheses, provide insight into disease mechanisms, and lead to predictive models. Throughout, we provide several examples demonstrating how bioinformatics contributes to systems medicine and discuss future challenges in bioinformatics that need to be addressed to enable the advancement of systems medicine. PMID- 26677178 TI - Systems Medicine: The Future of Medical Genomics, Healthcare, and Wellness. AB - Recent advances in genomics have led to the rapid and relatively inexpensive collection of patient molecular data including multiple types of omics data. The integration of these data with clinical measurements has the potential to impact on our understanding of the molecular basis of disease and on disease management. Systems medicine is an approach to understanding disease through an integration of large patient datasets. It offers the possibility for personalized strategies for healthcare through the development of a new taxonomy of disease. Advanced computing will be an important component in effectively implementing systems medicine. In this chapter we describe three computational challenges associated with systems medicine: disease subtype discovery using integrated datasets, obtaining a mechanistic understanding of disease, and the development of an informatics platform for the mining, analysis, and visualization of data emerging from translational medicine studies. PMID- 26677179 TI - Next-Generation Pathology. AB - The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care. PMID- 26677180 TI - Training in Systems Approaches for the Next Generation of Life Scientists and Medical Doctors. AB - The last decades have challenged us with novel technologies and abilities to look deep into the human genome of each individual, to screen for numerous metabolites in the blood, to search organs by imaging techniques, and much more. We can collect data from all these measurements from humans with different (usually multifactorial) diseases and, in accordance with ethical rules, store the data safely, locally, or remotely. The human data is growing exponentially, from giga- (10(9)), tera- (10(12)) to peta- (10(15)) and zettabytes (10(21)), both in public and restricted access settings. However, everyone agrees that the technological and information booms have not yet sufficiently reached medicine and have so far only barely influenced the clinical settings. In this chapter, we discuss the opinion that without topping up the education system, it will be difficult to catch up. We propose that in addition to the classical medical education, which is traditionally good and highly respected in European countries, we must find ways on how to introduce into the medical curricula mathematical and big data aspects and insights. Only a global (systems) view on physiology and pathophysiology can break the Gordian knot of many multifactorial diseases where we still don't understand the complexity of disease causes nor we can predict or cure the disease. We believe that the breakthrough is in the systems and interdisciplinary education and training, as early as possible in professional careers. If medical and related students and professionals would be formally educated in such interdisciplinary manner, they could take this knowledge further towards applications in their daily medical practice. We describe the current challenges and scattered best practices of introducing the wider systems medicine topics into the medical education as well as possibilities for systems medicine training at the doctoral and lifelong levels. PMID- 26677181 TI - Systems Medicine in Pharmaceutical Research and Development. AB - The development of new drug therapies requires substantial and ever increasing investments from the pharmaceutical company. Ten years ago, the average time from early target identification and optimization until initial market authorization of a new drug compound took more than 10 years and involved costs in the order of one billion US dollars. Recent studies indicate even a significant growth of costs in the meanwhile, mainly driven by the increasing complexity of diseases addressed by pharmaceutical research.Modeling and simulation are proven approaches to handle highly complex systems; hence, systems medicine is expected to control the spiral of complexity of diseases and increasing costs. Today, the main focus of systems medicine applications in industry is on mechanistic modeling. Biological mechanisms are represented by explicit equations enabling insight into the cooperation of all relevant mechanisms. Mechanistic modeling is widely accepted in pharmacokinetics, but prediction from cell behavior to patients is rarely possible due to lacks in our understanding of the controlling mechanisms. Data-driven modeling aims to compensate these lacks by the use of advanced statistical and machine learning methods. Future progress in pharmaceutical research and development will require integrated hybrid modeling technologies allowing realization of the benefits of both mechanistic and data driven modeling. In this chapter, we sketch typical industrial application areas for both modeling techniques and derive the requirements for future technology development. PMID- 26677182 TI - Systems Medicine and Infection. AB - By using a systems-based approach, mathematical and computational techniques can be used to develop models that describe the important mechanisms involved in infectious diseases. An iterative approach to model development allows new discoveries to continually improve the model and ultimately increase the accuracy of predictions.SIR models are used to describe epidemics, predicting the extent and spread of disease. Genome-wide genotyping and sequencing technologies can be used to identify the biological mechanisms behind diseases. These tools help to build strategies for disease prevention and treatment, an example being the recent outbreak of Ebola in West Africa where these techniques were deployed.HIV is a complex disease where much is still to be learned about the virus and the best effective treatment. With basic mathematical modeling techniques, significant discoveries have been made over the last 20 years. With recent technological advances, the computational resources now available, and interdisciplinary cooperation, further breakthroughs are inevitable.In TB, modeling has traditionally been empirical in nature, with clinical data providing the fuel for this top-down approach. Recently, projects have begun to use data derived from laboratory experiments and clinical trials to create mathematical models that describe the mechanisms responsible for the disease.A systems medicine approach to infection modeling helps identify important biological questions that then direct future experiments, the results of which improve the model in an iterative cycle. This means that data from several model systems can be integrated and synthesized to explore complex biological systems. PMID- 26677183 TI - Systems Medicine for Lung Diseases: Phenotypes and Precision Medicine in Cancer, Infection, and Allergy. AB - Lung diseases cause an enormous socioeconomic burden. Four of them are among the ten most important causes of deaths worldwide: Pneumonia has the highest death toll of all infectious diseases, lung cancer kills the most people of all malignant proliferative disorders, chronic obstructive pulmonary disease (COPD) ranks third in mortality among the chronic noncommunicable diseases, and tuberculosis is still one of the most important chronic infectious diseases. Despite all efforts, for example, by the World Health Organization and clinical and experimental researchers, these diseases are still highly prevalent and harmful. This is in part due to the specific organization of tissue homeostasis, architecture, and immunity of the lung. Recently, several consortia have formed and aim to bring together clinical and molecular data from big cohorts of patients with lung diseases with novel experimental setups, biostatistics, bioinformatics, and mathematical modeling. This "systems medicine" concept will help to match the different disease modalities with adequate therapeutic and possibly preventive strategies for individual patients in the sense of precision medicine. PMID- 26677184 TI - Third-Kind Encounters in Biomedicine: Immunology Meets Mathematics and Informatics to Become Quantitative and Predictive. AB - The understanding of the immune response is right now at the center of biomedical research. There are growing expectations that immune-based interventions will in the midterm provide new, personalized, and targeted therapeutic options for many severe and highly prevalent diseases, from aggressive cancers to infectious and autoimmune diseases. To this end, immunology should surpass its current descriptive and phenomenological nature, and become quantitative, and thereby predictive.Immunology is an ideal field for deploying the tools, methodologies, and philosophy of systems biology, an approach that combines quantitative experimental data, computational biology, and mathematical modeling. This is because, from an organism-wide perspective, the immunity is a biological system of systems, a paradigmatic instance of a multi-scale system. At the molecular scale, the critical phenotypic responses of immune cells are governed by large biochemical networks, enriched in nested regulatory motifs such as feedback and feedforward loops. This network complexity confers them the ability of highly nonlinear behavior, including remarkable examples of homeostasis, ultra sensitivity, hysteresis, and bistability. Moving from the cellular level, different immune cell populations communicate with each other by direct physical contact or receiving and secreting signaling molecules such as cytokines. Moreover, the interaction of the immune system with its potential targets (e.g., pathogens or tumor cells) is far from simple, as it involves a number of attack and counterattack mechanisms that ultimately constitute a tightly regulated multi feedback loop system. From a more practical perspective, this leads to the consequence that today's immunologists are facing an ever-increasing challenge of integrating massive quantities from multi-platforms.In this chapter, we support the idea that the analysis of the immune system demands the use of systems-level approaches to ensure the success in the search for more effective and personalized immune-based therapies. PMID- 26677185 TI - Systems Medicine in Oncology: Signaling Network Modeling and New-Generation Decision-Support Systems. AB - Two different perspectives are the main focus of this book chapter: (1) A perspective that looks to the future, with the goal of devising rational associations of targeted inhibitors against distinct altered signaling-network pathways. This goal implies a sufficiently in-depth molecular diagnosis of the personal cancer of a given patient. A sufficiently robust and extended dynamic modeling will suggest rational combinations of the abovementioned oncoprotein inhibitors. The work toward new selective drugs, in the field of medicinal chemistry, is very intensive. Rational associations of selective drug inhibitors will become progressively a more realistic goal within the next 3-5 years. Toward the possibility of an implementation in standard oncologic structures of technologically sufficiently advanced countries, new (legal) rules probably will have to be established through a consensus process, at the level of both diagnostic and therapeutic behaviors.(2) The cancer patient of today is not the patient of 5-10 years from now. How to support the choice of the most convenient (and already clinically allowed) treatment for an individual cancer patient, as of today? We will consider the present level of artificial intelligence (AI) sophistication and the continuous feeding, updating, and integration of cancer related new data, in AI systems. We will also report briefly about one of the most important projects in this field: IBM Watson US Cancer Centers. Allowing for a temporal shift, in the long term the two perspectives should move in the same direction, with a necessary time lag between them. PMID- 26677186 TI - Neurological Diseases from a Systems Medicine Point of View. AB - The difficulty to understand, diagnose, and treat neurological disorders stems from the great complexity of the central nervous system on different levels of physiological granularity. The individual components, their interactions, and dynamics involved in brain development and function can be represented as molecular, cellular, or functional networks, where diseases are perturbations of networks. These networks can become a useful research tool in investigating neurological disorders if they are properly tailored to reflect corresponding mechanisms. Here, we review approaches to construct networks specific for neurological disorders describing disease-related pathology on different scales: the molecular, cellular, and brain level. We also briefly discuss cross-scale network analysis as a necessary integrator of these scales. PMID- 26677187 TI - Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine. AB - Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine. PMID- 26677188 TI - From Systems Understanding to Personalized Medicine: Lessons and Recommendations Based on a Multidisciplinary and Translational Analysis of COPD. AB - Systems medicine, using and adapting methods and approaches as developed within systems biology, promises to be essential in ongoing efforts of realizing and implementing personalized medicine in clinical practice and research. Here we review and critically assess these opportunities and challenges using our work on COPD as a case study. We find that there are significant unresolved biomedical challenges in how to unravel complex multifactorial components in disease initiation and progression producing different clinical phenotypes. Yet, while such a systems understanding of COPD is necessary, there are other auxiliary challenges that need to be addressed in concert with a systems analysis of COPD. These include information and communication technology (ICT)-related issues such as data harmonization, systematic handling of knowledge, computational modeling, and importantly their translation and support of clinical practice. For example, clinical decision-support systems need a seamless integration with new models and knowledge as systems analysis of COPD continues to develop. Our experience with clinical implementation of systems medicine targeting COPD highlights the need for a change of management including design of appropriate business models and adoption of ICT providing and supporting organizational interoperability among professional teams across healthcare tiers, working around the patient. In conclusion, in our hands the scope and efforts of systems medicine need to concurrently consider these aspects of clinical implementation, which inherently drives the selection of the most relevant and urgent issues and methods that need further development in a systems analysis of disease. PMID- 26677189 TI - RNA Systems Biology for Cancer: From Diagnosis to Therapy. AB - It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer. PMID- 26677190 TI - Mathematical Models of Pluripotent Stem Cells: At the Dawn of Predictive Regenerative Medicine. AB - Regenerative medicine, ranging from stem cell therapy to organ regeneration, is promising to revolutionize treatments of diseases and aging. These approaches require a perfect understanding of cell reprogramming and differentiation. Predictive modeling of cellular systems has the potential to provide insights about the dynamics of cellular processes, and guide their control. Moreover in many cases, it provides alternative to experimental tests, difficult to perform for practical or ethical reasons. The variety and accuracy of biological processes represented in mathematical models grew in-line with the discovery of underlying molecular mechanisms. High-throughput data generation led to the development of models based on data analysis, as an alternative to more established modeling based on prior mechanistic knowledge. In this chapter, we give an overview of existing mathematical models of pluripotency and cell fate, to illustrate the variety of methods and questions. We conclude that current approaches are yet to overcome a number of limitations: Most of the computational models have so far focused solely on understanding the regulation of pluripotency, and the differentiation of selected cell lineages. In addition, models generally interrogate only a few biological processes. However, a better understanding of the reprogramming process leading to ESCs and iPSCs is required to improve stem-cell therapies. One also needs to understand the links between signaling, metabolism, regulation of gene expression, and the epigenetics machinery. PMID- 26677191 TI - Network-Assisted Disease Classification and Biomarker Discovery. AB - Developing improved approaches for diagnosis, treatment, and prevention of diseases is a major goal of biomedical research. Therefore, the discovery of biomarker signatures from high-throughput "omics" data is an active research topic in the field of bioinformatics and systems medicine. A major issue is the low reproducibility and the limited biological interpretability of candidate biomarker signatures identified from high-throughput data. This impedes the use of discovered biomarker signatures into clinical applications. Currently, much focus is placed on developing strategies to improve reproducibility and interpretability. Researchers have fruitfully started to incorporate prior knowledge derived from pathways and molecular networks into the process of biomarker identification. In this chapter, after giving a general introduction to the problem of disease classification and biomarker discovery, we will review two types of network-assisted approaches: (1) approaches inferring activity scores for specific pathways which are subsequently used for classification and (2) approaches identifying subnetworks or modules of molecular networks by differential network analysis which can serve as biomarker signatures. PMID- 26677192 TI - Anatomy and Physiology of Multiscale Modeling and Simulation in Systems Medicine. AB - Systems medicine is the application of systems biology concepts, methods, and tools to medical research and practice. It aims to integrate data and knowledge from different disciplines into biomedical models and simulations for the understanding, prevention, cure, and management of complex diseases. Complex diseases arise from the interactions among disease-influencing factors across multiple levels of biological organization from the environment to molecules. To tackle the enormous challenges posed by complex diseases, we need a modeling and simulation framework capable of capturing and integrating information originating from multiple spatiotemporal and organizational scales. Multiscale modeling and simulation in systems medicine is an emerging methodology and discipline that has already demonstrated its potential in becoming this framework. The aim of this chapter is to present some of the main concepts, requirements, and challenges of multiscale modeling and simulation in systems medicine. PMID- 26677193 TI - Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study. AB - The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non-exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine. PMID- 26677194 TI - Modeling and Simulation Tools: From Systems Biology to Systems Medicine. AB - Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools. PMID- 26677195 TI - Reaction Mechanism of 3,4-Dinitrofuroxan Formation from Glyoxime: Dehydrogenation and Cyclization of Oxime. AB - The reaction pathway of the formation of 3,4-dinitrofuroxan from glyoxime is theoretically investigated under experimental conditions with 25 % nitric acid and dinitrogentetroxide reagents to clarify the mechanism of formation of a furoxan ring by glyoxime. The geometric configurations of minima and transition state species are optimized at the (U)B3LYP/6-311++G** level. The CCSD(T) and CASSCF(10e,8o)/CASSCF(9e,8o) single-point energy corrections at the same level are performed on top of the optimized geometries. A subsequent dynamic correlation by using NEVPT2/6-311++G**-level single-point energy calculations based on the CASSCF results is also performed to obtain accurate energy values. The formation reaction is analyzed from two processes: glyoxime nitration and 3,4 dinitroglyoxime (nitration product) oxidative cyclization. Calculation results indicate that the electrophilic substitution of nitronium ions from the protonated HNO3 and the abstraction of hydrogen ions by HNO3 molecules are requisites of glyoxime nitration. The formation of a furoxan ring from 3,4 dinitroglyoxime involves two possible mechanisms: 1) oxydehydrogenation by NO2 molecules and the subsequent torsion of NO radical groups to form a ring and 2) the alternation of dehydrogenation and cyclization. The intermediates and transition states in both routes exhibit monoradical and diradical characteristics. Singlet and triplet reactions are considered for the diradical species. Results show that the singlet reaction mechanism is more favorable for cyclization than the triplet reaction. The formation of a furoxan ring from oxime is in accordance with the stepwise intermolecular dehydrogenation and intramolecular torsion to the ring. PMID- 26677196 TI - Infection and Stroke: an Update on Recent Progress. AB - The role of infection in cerebrovascular disease is complex and remains incompletely understood. Over the last 5 years, investigators have made notable inroads in untangling this thorny topic. In this review, we examine these recent developments, concentrating on four aspects of the relationship between infection and stroke. We first discuss specific infectious agents as direct causes of stroke, focusing on recent work implicating herpesviruses and HIV in cerebral vasculopathy. We then discuss systemic infection of any type as a stroke trigger, focusing on the relationship of infection to timing of acute stroke, both in children and adults, as well as the role of vaccination in stroke prevention. We examine the evidence for chronic infection or "infectious burden" as a stroke risk factor. Finally, we discuss recent work on infection as a risk factor for increased morbidity after stroke, possible mechanisms mediating this effect, and the evidence for prophylactic antibiotics. PMID- 26677197 TI - IMAGING DIAGNOSIS-THE COMPUTED TOMOGRAPHIC APPEARANCE OF A GIANT CELL TUMOR AFFECTING THE MANDIBLE IN A PYGMY GOAT. AB - A 3-year-old male neutered pygmy goat presented for evaluation of a progressive mandibular swelling and inappetence. A computed tomographic (CT) scan of the head and thorax was performed under general anesthesia. Computed tomography revealed an extensive multiloculated, markedly expansile lesion within the right hemimandible, which involved the articular surface of the temporomandibular joint. The goat was euthanased due to a poor prognosis and postmortem examination confirmed the diagnostic imaging findings. Histopathology was strongly suggestive of a multinucleated giant cell tumor, therefore this condition should be considered as a differential diagnosis in goats presenting with expansile mandibular mass lesions. PMID- 26677199 TI - The Immunologic Complexity of Growing Up with Malaria--Is Scientific Understanding Coming of Age? AB - In the current issue of Clinical and Vaccine Immunology, Mandala et al. report changes in lymphocyte populations in children with uncomplicated malaria, severe malarial anemia, and cerebral malaria compared to controls (W. L. Mandala et al., Clin Vaccine Immunol 23:95-103, 2016, http://dx.doi.org/10.1128/CVI.00564-15). This commentary discusses the importance of understanding both helpful and detrimental aspects of the antimalarial immune response that are critical to malaria vaccine development and considers how these responses may relate to antimalarial vaccine safety and efficacy. PMID- 26677198 TI - Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease. AB - In 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a "peribronchiolar monocytic infiltration with some excess in eosinophils." Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4(+) T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates. PMID- 26677200 TI - Serum Concentrations of Antibodies against Outer Membrane Protein P6, Protein D, and T- and B-Cell Combined Antigenic Epitopes of Nontypeable Haemophilus influenzae in Children and Adults of Different Ages. AB - Nontypeable Haemophilus influenzae (NTHi) is one of the most common etiologies of acute otitis media, rhinosinusitis, and pneumonia. Outer membrane proteins (OMPs) are the main focus in new vaccine development against NTHi, as the H. influenzae type b (Hib) vaccine does not cover noncapsulated NTHi. The OMPs P6 and protein D are the most promising candidate antigens for an NTHi vaccine, and low antibody levels against them in serum may be correlated with infection caused by NTHi. In the current study, we measured the antibody titers against P6, protein D, and their T- and B-cell combined peptide epitopes in healthy individuals of different ages. We found that children <1 month old had the lowest antibody levels against NTHi P6, protein D, and their T- and B-cell combined antigenic epitopes. Antibody titers increased at ages 1 to 6 months, peaked at 7 months to 3 years, and remained high at 4 to 6 years. The antibody titers started to decrease after 6 years and were the lowest in the 21- to 30-year group. The geometric mean titers (GMTs) of T- and B-cell combined antigenic epitopes in P6 and protein D were positively correlated with those of the protein antigens. Among 12 peptides tested, P6-61, P6-123, and protein D-167 epitopes were better recognized than others in human serum. These findings might contribute to the development of an effective serotype-independent vaccine for H. influenzae. PMID- 26677201 TI - Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies. AB - The efficacy of the serotype 3 (ST3) pneumococcal conjugate vaccine (PCV) remains unclear. While the synthesis of capsular polysaccharide (CPS) of most serotypes is wzy dependent, the strains of two serotypes, 3 and 37, synthesize CPS by the synthase-dependent pathway, resulting in a polysaccharide that is not covalently linked to peptidoglycan and can be released during growth. We hypothesized that the release of CPS during growth reduces anti-type 3 CPS antibody-mediated protection and may explain the lower efficacy of the type 3 component of PCV than that of other PCVs. The in vitro-released CPS concentrations per 10(7) CFU of ST3 and ST37 strains were significantly higher than those for the ST1, ST4, ST6B, and ST14 strains. Following intraperitoneal (i.p.) injection in mice, blood concentrations of CPS were significantly higher for the ST3 than for the ST4/5 strains. The opsonophagocytic killing assay (OPKA) titer of anti-type 3 CPS antibody was significantly reduced by type 3 CPS, culture supernatant, or serum from Streptococcus pneumoniae ST3 strain WU2-infected mice. Mice were injected with capsule-specific antibodies and challenged i.p. with or without the addition of sterile culture supernatant containing type-specific CPS. The addition of 0.2 MUl of culture supernatant from WU2 inhibited passive protection, whereas 100 fold-more culture supernatant from S. pneumoniae ST4 strain TIGR4 was required for the inhibition of protection. We conclude that released type 3 CPS interferes with antibody-mediated killing and protection by anti-CPS antibodies. The relative failure of ST3 PCV may be due to CPS release, suggesting that alternative immunization approaches for ST3 may be necessary. PMID- 26677202 TI - Interleukin-17A as a Biomarker for Bovine Tuberculosis. AB - T helper 17 (Th17)-associated cytokines are integral to the immune responses to tuberculosis, initiating both protective and harmful inflammatory responses. The aim of the present study was to evaluate applied aspects of interleukin-17 (IL 17) biology in the context of Mycobacterium bovis infection of cattle. Using transcriptome sequencing (RNA-Seq), numerous Th17-associated cytokine genes (including IL-17A, IL-17F, IL-22, IL-19, and IL-27) were upregulated >9-fold in response to purified protein derivative stimulation of peripheral blood mononuclear cells from experimentally M. bovis-infected cattle. Protective vaccines elicited IL-17A, IL-17F, IL-22, and IL-27 responses. Reduced IL-17A responses by vaccine recipients, compared to nonvaccinated animals, at 2.5 weeks after M. bovis challenge correlated with reduced disease burdens. Additionally, IL-17A and interferon gamma (IFN-gamma) responses were highly correlated and exhibited similar diagnostic capacities. The present findings support the use of Th17-associated cytokines as biomarkers of infection and protection in the immune responses to bovine tuberculosis. PMID- 26677204 TI - Effects of coffee/caffeine on brain health and disease: What should I tell my patients? AB - Over the last decade, Food Regulation Authorities have concluded that coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one sitting (around 21/2 cups of coffee) or 400 mg daily (around 5 cups of coffee). In addition, caffeine has many positive actions on the brain. It can increase alertness and well-being, help concentration, improve mood and limit depression. Caffeine may disturb sleep, but only in sensitive individuals. It may raise anxiety in a small subset of particularly sensitive people. Caffeine does not seem to lead to dependence, although a minority of people experience withdrawal symptoms. Caffeine can potentiate the effect of regular analgesic drugs in headache and migraine. Lifelong coffee/caffeine consumption has been associated with prevention of cognitive decline, and reduced risk of developing stroke, Parkinson's disease and Alzheimer's disease. Its consumption does not seem to influence seizure occurrence. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet; its consumption does not need to be stopped in elderly people. PMID- 26677203 TI - Tubby-like protein superfamily member PLSCR3 functions as a negative regulator of adipogenesis in mouse 3T3-L1 preadipocytes by suppressing induction of late differentiation stage transcription factors. AB - PLSCR3 (phospholipid scramblase 3, Scr3) belongs to the superfamily of membrane associated transcription regulators named Tubby-like proteins (TULPs). Physiological phospholipid scrambling activities of PLSCRs in vivo have been skeptically argued, and knowledge of the biological functions of Scr3 is limited. We investigated the expression of Scr3 during differentiation of mouse 3T3-L1 preadipocytes by Western blotting (WB) and by reverse-transcription and real-time quantitative PCR (RT-qPCR). The Scr3 protein decreased during 3T3-L1 differentiation accompanied by a reduction in the mRNA level, and there was a significant increase in the amount of Scr3 protein secreted into the culture medium in the form of extracellular microvesicles (exosomes). On the other hand, Scr3 expression did not significantly decrease, and the secretion of Scr3 in 3T3 Swiss-albino fibroblasts (a parental cell-line of 3T3-L1) was not increased by differentiation treatment. Overexpression of human Scr3 during 3T3-L1 differentiation suppressed triacylglycerol accumulation and inhibited induction of the mRNAs of late stage pro-adipogenic transcription factors [CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma)] and X-box-binding protein 1 (XBP1). Expression of early stage pro-adipogenic transcription factors (C/EBPbeta and C/EBPdelta) was not significantly affected. These results suggest that Scr3 functions as a negative regulator of adipogenesis in 3T3-L1 cells at a specific differentiation stage and that decrease in the intracellular amount of Scr3 protein caused by reduction in Scr3 mRNA expression and enhanced secretion of Scr3 protein appears to be important for appropriate adipocyte differentiation. PMID- 26677205 TI - Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry. AB - BACKGROUND: The extent to which clinical breast cancer risk prediction models can be improved by including information on known susceptibility SNPs is not known. METHODS: Using 750 cases and 405 controls from the population-based Australian Breast Cancer Family Registry who were younger than 50 years at diagnosis and recruitment, respectively, Caucasian and not BRCA1 or BRCA2 mutation carriers, we derived absolute 5-year risks of breast cancer using the BOADICEA, BRCAPRO, BCRAT, and IBIS risk prediction models and combined these with a risk score based on 77 independent risk-associated SNPs. We used logistic regression to estimate the OR per adjusted SD for log-transformed age-adjusted 5-year risks. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. We also constructed reclassification tables and calculated the net reclassification improvement. RESULTS: The ORs for BOADICEA, BRCAPRO, BCRAT, and IBIS were 1.80, 1.75, 1.67, and 1.30, respectively. When combined with the SNP-based score, the corresponding ORs were 1.96, 1.89, 1.80, and 1.52. The corresponding AUCs were 0.66, 0.65, 0.64, and 0.57 for the risk prediction models, and 0.70, 0.69, 0.66, and 0.63 when combined with the SNP-based score. CONCLUSIONS: By combining a 77 SNP-based score with clinical models, the AUC for predicting breast cancer before age 50 years improved by >20%. IMPACT: Our estimates of the increased performance of clinical risk prediction models from including genetic information could be used to inform targeted screening and prevention. PMID- 26677207 TI - Exploring the Feasibility of a Broad-Reach Physical Activity Behavior Change Intervention for Women Receiving Chemotherapy for Breast Cancer: A Randomized Trial. AB - BACKGROUND: Facilitating healthy levels of physical activity (PA) during chemotherapy is important for the psychosocial and physical health of breast cancer survivors. The primary objective of this feasibility study was to examine the effects of a broad-reach PA behavior change intervention among women with breast cancer receiving adjuvant chemotherapy. METHODS: Breast cancer patients receiving adjuvant chemotherapy (N = 95) were randomly assigned to receive a PA resource kit consisting of tailored print materials and a step pedometer (intervention) or a standard public health PA recommendation (standard recommendation). The primary outcome was daily pedometer steps. Secondary outcomes were self-reported light, moderate, and vigorous intensity PA, total moderate-to-vigorous PA, and sedentary time. Assessments were conducted before and after adjuvant chemotherapy. RESULTS: Attrition was 19% (17 of 95). Intervention patients wore their step pedometer for 85 days (range, 35-144 days; SD = 26.4) for a 95% adherence rate. Analyses of covariance suggested that the intervention was not statistically superior to standard recommendation for daily average pedometer steps (-771; 95% CI = -2024 to 482; P = 0.22), total MVPA minutes (-4; 95% CI = -62 to 570; P = 0.90), or sedentary time (+160; 95% CI = 186 to 506; P = 0.42). CONCLUSION: This broach-reach and low intensive intervention was not more effective for promoting PA in breast cancer patients receiving chemotherapy than providing the standard public health guidelines for PA. IMPACT: Achieving physical activity behavior change during adjuvant breast cancer chemotherapy may require some level of supervised physical activity or more intensive (e.g., face-to-face, supervised) interventions. PMID- 26677206 TI - Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity. AB - BACKGROUND: Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity. METHODS: The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species. RESULTS: Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. CONCLUSIONS: Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. IMPACT: This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles. PMID- 26677208 TI - Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study. AB - BACKGROUND: Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer. METHODS: We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer. RESULTS: In 1987, 2% of men reported sleeping <=5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15-8.10). CONCLUSIONS: We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes. IMPACT: We did not find support for a consistent association between self reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men. PMID- 26677209 TI - Polymorphisms of a Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 and Aflatoxin B1-Related Hepatocellular Carcinoma. AB - BACKGROUND: Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related hepatocellular carcinoma have not yet been elucidated. METHODS: We conducted a hospital-based case-control study, including 1,706 hepatocellular carcinoma cases and 2,270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related hepatocellular carcinoma risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and microvessel density were analyzed by IHC. RESULTS: Among these 74 polymorphisms, only rs2830581 affected hepatocellular carcinoma risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased hepatocellular carcinoma risk (OR: 1.85 and 4.40; 95% CI: 1.57-2.19 and 3.43-5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathologic features of hepatocellular carcinoma such as tumor dedifferentiation and microvessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on hepatocellular carcinoma. CONCLUSIONS: These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related hepatocellular carcinoma, and rs2830581 is a potential candidate. IMPACT: Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1 related hepatocellular carcinoma risk and prognosis. PMID- 26677210 TI - Variants in 6q25.1 Are Associated with Mammographic Density in Malaysian Chinese Women. AB - BACKGROUND: Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort. METHODS: We conducted genotyping by mass spectrometry in 1,189 women (865 Chinese, 187 Indian, and 137 Malay). Quantitative measurements of mammographic density were performed using ImageJ, a fully automated thresholding technique. The associations of SNPs to densities were analyzed using linear regression models. RESULTS: We successfully evaluated the associations of 36 SNPs with mammographic densities. After adjusting for age, body mass index, parity, and menopausal status, we found that in our cohort of 865 Malaysian Chinese, three SNPs in the 6q25.1 region near ESR1 (rs2046210, rs12173570, and rs10484919) that were associated with mammographic density, breast cancer risk, or breast size in previous GWAS were significantly associated with both percentage density and absolute dense area. We could not replicate the most significant association found previously in European women (rs10995190, ZNF365 gene) because the minor allele was absent for Asian women. CONCLUSION: We found that the directions of genetic associations were similar to those reported in Caucasian women. IMPACT: Our results show that even in Asian women with lower population risk to breast cancer, there is shared heritability between mammographic density and breast cancer risk. PMID- 26677211 TI - Summer Peaks in Uptake of Human Papillomavirus and Other Adolescent Vaccines in the United States. AB - BACKGROUND: Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. METHODS: Data came from health care provider-verified vaccination records for 70,144 adolescents (ages 13-17 years) from the 2008 to 2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in the uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. RESULTS: Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all P < 0.001). Uptake was five times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all P < 0.001). CONCLUSION: Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. IMPACT: The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. PMID- 26677213 TI - The Influence of Exercise on the Insulin-like Growth Factor Axis in Oncology: Physiological Basis, Current, and Future Perspectives. AB - Exercise and physical activity have been shown to reduce the risk of many common cancers and strongly influence tumor biology. A cause-effect mechanism explaining this relationship is dependent on cellular pathways that can influence tumor growth and are exercise responsive. The insulin-like growth factor (IGF) axis is reported to promote the development and progression of carcinomas through cellular signaling in cancerous tissues. This review summarizes the physiologic basis of the role of the IGF axis in oncology and the influence of exercise on this process. We examined the effects of exercise prescription on the IGF axis in cancer survivors by evaluating the current scope of the literature. The current research demonstrates a remarkable heterogeneity and inconsistency in the responses of the IGF axis to exercise in breast, prostate, and colorectal cancer survivors. Finally, this review presents an in-depth exploration of the physiologic basis and mechanistic underpinnings of the seemingly disparate relationship between exercise and the IGF axis in oncology. Although there is currently insufficient evidence to categorize the effects of exercise prescription on the IGF axis in cancer survivors, the inconsistency of results suggests a multifaceted relationship, the complexities of which are considered in this review. PMID- 26677212 TI - Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients. AB - BACKGROUND: Gut barrier dysfunction contributes to several gastrointestinal disorders, including colorectal cancer, but factors associated with intestinal hyperpermeability have been minimally studied in humans. METHODS: We tested the effects of two doses of calcium (1.0 or 2.0 g/d) on circulating biomarkers of gut permeability [anti-flagellin and anti-lipopolysaccharide (LPS) Ig, measured via ELISA] over a 4-month treatment period among colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193), and evaluated the factors associated with baseline levels of these biomarkers. RESULTS: Baseline concentrations of anti-flagellin IgA and anti-LPS IgA were, respectively, statistically significantly proportionately higher by 11.8% and 14.1% among men, 31.3% and 39.8% among those with a body mass index >= 35 kg/m(2), and 19.9% and 22.0% among those in the upper relative to the lowest sex specific tertile of waist circumference. A combined permeability score (the summed optical densities of all four biomarkers) was 24.3% higher among women in the upper tertile of plasma C-reactive protein (Ptrend < 0.01). We found no appreciable effects of supplemental calcium on anti-flagellin or anti-LPS Igs. CONCLUSIONS: Our results suggest that (i) men and those with higher adiposity may have greater gut permeability, (ii) gut permeability and systemic inflammation may be directly associated with one another, and (iii) supplemental calcium may not modify circulating levels of gut permeability biomarkers within 4 months. IMPACT: Our findings may improve the understanding of the factors that influence gut permeability to inform development of treatable biomarkers of risk for colorectal cancer and other health outcomes. PMID- 26677214 TI - Tip of the iceberg: patient safety incidents in primary care. PMID- 26677216 TI - Editorial: Celebrating 40 years of the Journal. PMID- 26677215 TI - From the closest observers of patient care: a thematic analysis of online narrative reviews of hospitals. AB - OBJECTIVE: Patient-centred care has become a priority in many countries. It is unknown whether current tools capture aspects of care patients and their surrogates consider important. We investigated whether online narrative reviews from patients and surrogates reflect domains in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and we described additional potential domains. DESIGN: We used thematic analysis to assess online narrative reviews for reference to HCAHPS domains and salient non-HCAHPS domains and compared results by reviewer type (patient vs surrogate). SETTING: We identified hospitals for review from the American Hospital Association database using a stratified random sampling approach. This approach ensured inclusion of reviews of a diverse set of hospitals. We searched online in February 2013 for narrative reviews from any source for each hospital. PARTICIPANTS: We included up to two narrative reviews for each hospital. EXCLUSIONS: Outpatient or emergency department reviews, reviews from self-identified hospital employees, or reviews of <10 words. RESULTS: 50.0% (n=122) of reviews (N=244) were from patients and 38.1% (n=93) from friends or family members. Only 57.0% (n=139) of reviews mentioned any HCAHPS domain. Additional salient domains were: Financing, including unexpected out-of-pocket costs and difficult interactions with billing departments; system-centred care; and perceptions of safety. These domains were mentioned in 51.2% (n=125) of reviews. Friends and family members commented on perceptions of safety more frequently than patients. CONCLUSIONS: A substantial proportion of consumer reviews do not mention HCAHPS domains. Surrogates appear to observe care differently than patients, particularly around safety. PMID- 26677217 TI - Modulation of Potassium Channels Inhibits Bunyavirus Infection. AB - Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare, and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K(+)) channels to infect cells. Time of addition assays using K(+) channel modulating agents demonstrated that K(+) channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K(+) channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, two-pore domain K(+) channels (K2P) were identified as the K(+) channel family mediating BUNV K(+) channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease. PMID- 26677218 TI - Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina. AB - Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternatively, production can be set by a signal that anticipates demand. In this report we investigate the hypothesis that signaling through phototransduction controls production of energy in mouse retinas. We found that respiration in mouse retinas is not coupled tightly to ATP consumption. By analyzing metabolic flux in mouse retinas, we also found that phototransduction slows metabolic flux through glycolysis and through intermediates of the citric acid cycle. We also evaluated the relative contributions of regulation of the activities of alpha-ketoglutarate dehydrogenase and the aspartate-glutamate carrier 1. In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines. PMID- 26677219 TI - Pseudomonas aeruginosa EftM Is a Thermoregulated Methyltransferase. AB - Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that trimethylates elongation factor-thermo-unstable (EF-Tu) on lysine 5. Lysine 5 methylation occurs in a temperature-dependent manner and is generally only seen when P. aeruginosa is grown at temperatures close to ambient (25 degrees C) but not at higher temperatures (37 degrees C). We have previously identified the gene, eftM (for EF-Tu-modifying enzyme), responsible for this modification and shown its activity to be associated with increased bacterial adhesion to and invasion of respiratory epithelial cells. Bioinformatic analyses predicted EftM to be a Class I S-adenosyl-l-methionine (SAM)-dependent methyltransferase. An in vitro methyltransferase assay was employed to show that, in the presence of SAM, EftM directly trimethylates EF-Tu. A natural variant of EftM, with a glycine to arginine substitution at position 50 in the predicted SAM-binding domain, lacks both SAM binding and enzyme activity. Mass spectrometry analysis of the in vitro methyltransferase reaction products revealed that EftM exclusively methylates at lysine 5 of EF-Tu in a distributive manner. Consistent with the in vivo temperature dependence of methylation of EF-Tu, preincubation of EftM at 37 degrees C abolished methyltransferase activity, whereas this activity was retained when EftM was preincubated at 25 degrees C. Irreversible protein unfolding at 37 degrees C was observed, and we propose that this instability is the molecular basis for the temperature dependence of EftM activity. Collectively, our results show that EftM is a thermolabile, SAM-dependent methyltransferase that directly trimethylates lysine 5 of EF-Tu in P. aeruginosa. PMID- 26677220 TI - C-terminal Domain of Leucyl-tRNA Synthetase from Pathogenic Candida albicans Recognizes both tRNASer and tRNALeu. AB - Leucyl-tRNA synthetase (LeuRS) is a multidomain enzyme that catalyzes Leu tRNA(Leu) formation and is classified into bacterial and archaeal/eukaryotic types with significant diversity in the C-terminal domain (CTD). CTDs of both bacterial and archaeal LeuRSs have been reported to recognize tRNA(Leu) through different modes of interaction. In the human pathogen Candida albicans, the cytoplasmic LeuRS (CaLeuRS) is distinguished by its capacity to recognize a uniquely evolved chimeric tRNA(Ser) (CatRNA(Ser)(CAG)) in addition to its cognate CatRNA(Leu), leading to CUG codon reassignment. Our previous study showed that eukaryotic but not archaeal LeuRSs recognize this peculiar tRNA(Ser), suggesting the significance of their highly divergent CTDs in tRNA(Ser) recognition. The results of this study provided the first evidence of the indispensable function of the CTD of eukaryotic LeuRS in recognizing non-cognate CatRNA(Ser) and cognate CatRNA(Leu). Three lysine residues were identified as involved in mediating enzyme-tRNA interaction in the leucylation process: mutation of all three sites totally ablated the leucylation activity. The importance of the three lysine residues was further verified by gel mobility shift assays and complementation of a yeast leuS gene knock-out strain. PMID- 26677221 TI - Mitochondrial Sulfide Quinone Oxidoreductase Prevents Activation of the Unfolded Protein Response in Hydrogen Sulfide. AB - Hydrogen sulfide (H2S) is an endogenously produced gaseous molecule with important roles in cellular signaling. In mammals, exogenous H2S improves survival of ischemia/reperfusion. We have previously shown that exposure to H2S increases the lifespan and thermotolerance in Caenorhabditis elegans, and improves protein homeostasis in low oxygen. The mitochondrial SQRD-1 (sulfide quinone oxidoreductase) protein is a highly conserved enzyme involved in H2S metabolism. SQRD-1 is generally considered important to detoxify H2S. Here, we show that SQRD-1 is also required to maintain protein translation in H2S. In sqrd 1 mutant animals, exposure to H2S leads to phosphorylation of eIF2alpha and inhibition of protein synthesis. In contrast, global protein translation is not altered in wild-type animals exposed to lethally high H2S or in hif-1(ia04) mutants that die when exposed to low H2S. We demonstrate that both gcn-2 and pek 1 kinases are involved in the H2S-induced phosphorylation of eIF2alpha. Both ER and mitochondrial stress responses are activated in sqrd-1 mutant animals exposed to H2S, but not in wild-type animals. We speculate that SQRD-1 activity in H2S may coordinate proteostasis responses in multiple cellular compartments. PMID- 26677222 TI - Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains. AB - By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-beta family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9.pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9.pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants. PMID- 26677223 TI - Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor. AB - Unusually large von Willebrand factor (VWF), the first responder to vascular injury in primary hemostasis, is designed to capture platelets under the high shear stress of rheological blood flow. In type 2M von Willebrand disease, two rare mutations (G1324A and G1324S) within the platelet GPIbalpha binding interface of the VWF A1 domain impair the hemostatic function of VWF. We investigate structural and conformational effects of these mutations on the A1 domain's efficacy to bind collagen and adhere platelets under shear flow. These mutations enhance the thermodynamic stability, reduce the rate of unfolding, and enhance the A1 domain's resistance to limited proteolysis. Collagen binding affinity is not significantly affected indicating that the primary stabilizing effect of these mutations is to diminish the platelet binding efficiency under shear flow. The enhanced stability stems from the steric consequences of adding a side chain (G1324A) and additionally a hydrogen bond (G1324S) to His(1322) across the beta2-beta3 hairpin in the GPIbalpha binding interface, which restrains the conformational degrees of freedom and the overall flexibility of the native state. These studies reveal a novel rheological strategy in which the incorporation of a single glycine within the GPIbalpha binding interface of normal VWF enhances the probability of local unfolding that enables the A1 domain to conformationally adapt to shear flow while maintaining its overall native structure. PMID- 26677224 TI - Identification of the Glycosaminoglycan Binding Site of Interleukin-10 by NMR Spectroscopy. AB - The biological function of interleukin-10 (IL-10), a pleiotropic cytokine with an essential role in inflammatory processes, is known to be affected by glycosaminoglycans (GAGs). GAGs are highly negatively charged polysaccharides and integral components of the extracellular matrix with important functions in the biology of many growth factors and cytokines. The molecular mechanism of the IL 10/GAG interaction is unclear. In particular, experimental evidence about IL 10/GAG binding sites is lacking, despite its importance for understanding the biological role of the interaction. Here, we report the experimental determination of a GAG binding site of IL-10. Although no co-crystal structure of the IL-10.GAG complex could be obtained, its structural characterization was possible by NMR spectroscopy. Chemical shift perturbations of IL-10 induced by GAG binding were used to narrow down the location of the binding site and to assess the affinity for different GAG molecules. Subsequent observation of NMR pseudocontact shifts of IL-10 and its heparin ligand, as induced by a protein attached lanthanide spin label, provided structural restraints for the protein.ligand complex. Using these restraints, pseudocontact shift-based rigid body docking together with molecular dynamics simulations yielded a GAG binding model. The heparin binding site is located at the C-terminal end of helix D and the adjacent DE loop and coincides with a patch of positively charged residues involving arginines 102, 104, 106, and 107 and lysines 117 and 119. This study represents the first experimental characterization of the IL-10.GAG complex structure and provides the starting point for revealing the biological significance of the interaction of IL-10 with GAGs. PMID- 26677225 TI - Introduction to the Minireview Series on Modern Technologies for In-cell Biochemistry. AB - The last decade has seen enormous progress in the exploration and understanding of the behavior of molecules in their natural cellular environments at increasingly high spatial and temporal resolution. Advances in microscopy and the development of new fluorescent reagents as well as genetic editing techniques have enabled quantitative analysis of protein interactions, intracellular trafficking, metabolic changes, and signaling. Modern biochemistry now faces new and exciting challenges. Can traditionally "in vitro" experiments, e.g. analysis of protein folding and conformational transitions, be done in cells? Can the structure and behavior of endogenous and/or non-tagged recombinant proteins be analyzed and altered within the cell or in cellular compartments? How can molecules and their actions be studied mechanistically in tissues and organs? Is personalized cellular biochemistry a reality? This thematic series summarizes recent studies that illustrate some first steps toward successfully answering these modern biochemical questions. The first minireview focuses on utilization of three-dimensional primary enteroids and organoids for mechanistic studies of intestinal biology with molecular resolution. The second minireview describes application of single chain antibodies (nanobodies) for monitoring and regulating protein dynamics in vitro and in cells. The third minireview highlights advances in using NMR spectroscopy for analysis of protein folding and assembly in cells. PMID- 26677226 TI - The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival. AB - To interpret epigenetic information, chromatin readers utilize various protein domains for recognition of DNA and histone modifications. Some readers possess multidomains for modification recognition and are thus multivalent. Bromodomain- and plant homeodomain-linked finger-containing protein 3 (BRPF3) is such a chromatin reader, containing two plant homeodomain-linked fingers, one bromodomain and a PWWP domain. However, its molecular and biological functions remain to be investigated. Here, we report that endogenous BRPF3 preferentially forms a tetrameric complex with HBO1 (also known as KAT7) and two other subunits but not with related acetyltransferases such as MOZ, MORF, TIP60, and MOF (also known as KAT6A, KAT6B, KAT5, and KAT8, respectively). We have also characterized a mutant mouse strain with a lacZ reporter inserted at the Brpf3 locus. Systematic analysis of beta-galactosidase activity revealed dynamic spatiotemporal expression of Brpf3 during mouse embryogenesis and high expression in the adult brain and testis. Brpf3 disruption, however, resulted in no obvious gross phenotypes. This is in stark contrast to Brpf1 and Brpf2, whose loss causes lethality at E9.5 and E15.5, respectively. In Brpf3-null mice and embryonic fibroblasts, RT-quantitative PCR uncovered no changes in levels of Brpf1 and Brpf2 transcripts, confirming no compensation from them. These results indicate that BRPF3 forms a functional tetrameric complex with HBO1 but is not required for mouse development and survival, thereby distinguishing BRPF3 from its paralogs, BRPF1 and BRPF2. PMID- 26677227 TI - Ras Regulates Rb via NORE1A. AB - Mutations in the Ras oncogene are one of the most frequent events in human cancer. Although Ras regulates numerous growth-promoting pathways to drive transformation, it can paradoxically promote an irreversible cell cycle arrest known as oncogene-induced senescence. Although senescence has clearly been implicated as a major defense mechanism against tumorigenesis, the mechanisms by which Ras can promote such a senescent phenotype remain poorly defined. We have shown recently that the Ras death effector NORE1A plays a critical role in promoting Ras-induced senescence and connects Ras to the regulation of the p53 tumor suppressor. We now show that NORE1A also connects Ras to the regulation of a second major prosenescent tumor suppressor, the retinoblastoma (Rb) protein. We show that Ras induces the formation of a complex between NORE1A and the phosphatase PP1A, promoting the activation of the Rb tumor suppressor by dephosphorylation. Furthermore, suppression of Rb reduces NORE1A senescence activity. These results, together with our previous findings, suggest that NORE1A acts as a critical tumor suppressor node, linking Ras to both the p53 and the Rb pathways to drive senescence. PMID- 26677228 TI - Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology. AB - Identification of Lgr5 as the intestinal stem cell marker as well as the growth factors necessary to replicate adult intestinal stem cell division has led to the establishment of the methods to generate "indefinite" ex vivo primary intestinal epithelial cultures, termed "mini-intestines." Primary cultures developed from isolated intestinal crypts or stem cells (termed enteroids/colonoids) and from inducible pluripotent stem cells (termed intestinal organoids) are being applied to study human intestinal physiology and pathophysiology with great expectations for translational applications, including regenerative medicine. Here we discuss the physiologic properties of these cultures, their current use in understanding diarrhea-causing host-pathogen interactions, and potential future applications. PMID- 26677229 TI - A Unique Tool for Cellular Structural Biology: In-cell NMR. AB - Conventional structural and chemical biology approaches are applied to macromolecules extrapolated from their native context. When this is done, important structural and functional features of macromolecules, which depend on their native network of interactions within the cell, may be lost. In-cell nuclear magnetic resonance is a branch of biomolecular NMR spectroscopy that allows macromolecules to be analyzed in living cells, at the atomic level. In cell NMR can be applied to several cellular systems to obtain biologically relevant structural and functional information. Here we summarize the existing approaches and focus on the applications to protein folding, interactions, and post-translational modifications. PMID- 26677232 TI - An Independent Evaluation of the Validity of a DNA-Based Prognostic Test for Adolescent Idiopathic Scoliosis. AB - BACKGROUND: ScoliScore is a DNA-based prognostic test, designed and used to help to predict the risk of curve progression in patients with adolescent idiopathic scoliosis. The role of this test in clinical practice remains unclear as the published results of the ScoliScore have not been validated independently. The purpose of this study was to determine if the ScoliScore effectively predicted the risk of curve progression in patients with mild and moderate adolescent idiopathic scoliosis in two urban academic medical centers. METHODS: One hundred and twenty-six patients with adolescent idiopathic scoliosis who met inclusion criteria at two centers were administered the ScoliScore test. Two groups were created: a progression group (those who had a Cobb angle of >40 degrees or those who had undergone surgical fusion) and a non-progression group (those who had skeletal maturity without curve progression to 40 degrees ). ScoliScore values and risk levels were compared between the two groups. The negative predictive value was calculated for low-risk scores and the positive predictive value was calculated for high-risk scores. RESULTS: There was no significant difference (p = 0.706) in the mean ScoliScore (and standard deviation) between patients with curve progression (107 +/- 55 points) and those without curve progression (102 +/ 62 points). There was also no significant difference (p = 0.399) in curve progression between patients with high-risk scores (26.7%) and those with low risk scores (12.9%). The positive predictive value of the test was 0.27 (95% confidence interval, 0.09 to 0.55), and the negative predictive value was 0.87 (95% confidence interval, 0.69 to 0.96). ScoliScores and rates of progression were not affected by brace-wear. CONCLUSIONS: ScoliScores did not differ between patients with and without curve progression, and the negative and positive predictive values were lower in our study than in the previously published validation study by the developers of the test. This may be due to differences in our test population, genetic variability, or failure of patients in the non progression group to follow up. PMID- 26677233 TI - Psychological Distress Is Associated with Greater Perceived Disability and Pain in Patients Presenting to a Shoulder Clinic. AB - BACKGROUND: Shoulder disorders are a common cause of disability and pain. The Shoulder Pain and Disability Index (SPADI) is a frequently employed and previously validated measure of shoulder pain and disability. Although the SPADI has high reliability and construct validity, greater differences between individual patients are often observed than would be expected on the basis of diagnosis and pathophysiology alone. This study aims to determine how psychological factors (namely depression, catastrophic thinking, and self efficacy) affect pain and perceived disability in the shoulder. METHODS: A cohort of 139 patients completed a sociodemographic survey and elements from the SPADI, Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), and Patient Health Questionnaire Depression Scale (PHQ-2). Bivariate and multivariate analyses were performed to determine the association of psychosocial factors, demographic characteristics, and specific diagnosis with shoulder pain and disability. RESULTS: The SPADI score showed medium correlation with the PCS (r = 0.43; p < 0.001), PHQ-2 (r = 0.39; p < 0.001), and PSEQ (r = -0.45; p < 0.001). Current work status (F = 4.35; p = 0.006) and body mass index (r = 0.27; p = 0.002) were also associated with the SPADI score. In the multivariate analysis, greater catastrophic thinking (estimate, 0.003; p = 0.029), lower self-efficacy (estimate, -0.005; p = 0.001), higher body mass index (estimate, 0.006; p = 0.048), and being disabled (estimate, 0.15; p = 0.017) or retired (estimate, 0.16; p < 0.001) compared with being employed were associated with worse SPADI scores. The primary diagnosis did not have a significant relationship (p > 0.05) with the SPADI. CONCLUSIONS: Catastrophic thinking and decreased self-efficacy are associated with greater shoulder pain and disability. Our data support the notion that patient-to-patient variation in symptom intensity and magnitude of disability is more strongly related to psychological distress than to the specific shoulder diagnosis. PMID- 26677230 TI - Nanobodies as Probes for Protein Dynamics in Vitro and in Cells. AB - Nanobodies are the recombinant antigen-recognizing domains of the minimalistic heavy chain-only antibodies produced by camels and llamas. Nanobodies can be easily generated, effectively optimized, and variously derivatized with standard molecular biology protocols. These properties have triggered the recent explosion in the nanobody use in basic and clinical research. This review focuses on the emerging use of nanobodies for understanding and monitoring protein dynamics on the scales ranging from isolated protein domains to live cells, from nanoseconds to hours. The small size and high solubility make nanobodies uniquely suited for studying protein dynamics by NMR. The ability to produce conformation-sensitive nanobodies in cells enables studies that link structural dynamics of a target protein to its cellular behavior. The link between in vitro and in-cell dynamics, afforded by nanobodies, brings the analysis of such important events as receptor signaling, membrane protein trafficking, and protein interactions to the next level of resolution. PMID- 26677234 TI - Conversion of Tibiotalar Arthrodesis to Total Ankle Arthroplasty. AB - BACKGROUND: Conversion of ankle arthrodesis to total ankle arthroplasty remains controversial. Although satisfactory outcomes have been published, not all foot and ankle surgeons performing total ankle arthroplasty have embraced this modality. METHODS: Twenty-three total ankle arthroplasties were performed in patients who had undergone a prior or an attempted ankle arthrodesis. The mean age at surgery was fifty-nine years (range, forty-one to eighty years), and the mean duration of follow-up was 33.1 months (minimum, twelve months). Indications for the procedure were symptomatic adjacent hindfoot arthritis (twelve patients) or symptomatic tibiotalar or subtalar nonunion (eleven) after tibiotalocalcaneal arthrodesis. We performed concomitant surgical procedures in eighteen ankles (78%), with the most common procedure being prophylactic malleolar fixation (70%). We prospectively evaluated clinical outcomes using the Short Form-36 (SF 36), Short Musculoskeletal Function Assessment (SMFA), and visual analog scale (VAS) for pain and assessed initial weight-bearing radiographs and those made at the most recent follow-up evaluation. RESULTS: The mean VAS pain score (and standard deviation) improved from 65.7 +/- 21.8 preoperatively to 18.3 +/- 17.6 at the most recent follow-up evaluation (p < 0.001), with five patients being pain-free (VAS score = 0). The mean SMFA bother and function indexes improved from 55 +/- 22.9 and 46.7 +/- 12.6 preoperatively to 30.6 +/- 22.7 and 25.4 +/- 17.4 at the most recent follow-up visit (p = 0.001 and p < 0.001, respectively). The mean SF-36 total score improved from 37.7 +/- 19.3 to 56.4 +/- 23.1 (p = 0.002). The implant survival rate was 87%. Four (20%) of the tibial components and fourteen (70%) of the talar components that were not revised exhibited initial settling and then were seen to be stabilized radiographically without further change in implant position. Three total ankle replacements (13%) showed progressive talar subsidence, prompting revision. Ten patients (43%) had minor complications not requiring repeat surgery. CONCLUSIONS: Short-term follow-up after conversion of ankle arthrodesis to total ankle arthroplasty demonstrated pain relief and improved function in a majority of patients. Patients who undergo this surgery frequently require concomitant procedures; we recommend prophylactic malleolar fixation when performing conversion total ankle arthroplasty. The rate of complications, particularly talar component settling and migration, is cause for concern. We do not recommend the procedure for ankle arthrodeses that included distal fibulectomy. PMID- 26677235 TI - The Importance of Preserving the Radial Tuberosity During Distal Biceps Repair. AB - BACKGROUND: The radial tuberosity contributes to the biceps supination moment arm and the elbow flexion moment. The purpose of our study was to compare the impact of a cortical bone trough versus an anatomic repair on measurements of the forearm supination moment arm and elbow flexion force efficiency. Our hypothesis was that a trough repair would decrease the tuberosity height, the native biceps supination moment arm, and elbow flexion force efficiency compared with an anatomic repair. METHODS: The isometric supination moment arm and elbow flexion force efficiency were measured in ten matched pairs of cadaveric upper limbs. After testing, the geometry of the proximal aspect of the radius was reconstructed with use of stereophotogrammetry. All of the repair sites were three-dimensionally reconstructed to quantify the disturbance of the trough on native anatomy. The tuberosity distance was defined as the distance between the central axis of the radius and the centroid of the respective repair site. RESULTS: Specimens with a trough repair had a 27% lower supination moment arm at 60 degrees of supination (p = 0.036). There were no differences found for pronation or neutral forearm positioning (p > 0.235). Flexion force efficiency was not significantly different between the trough and anatomic repair groups. The average tuberosity distance was 11.0 +/- 2.1 mm for the anatomic repairs and 8.3 +/- 1.4 mm for the trough repairs (p = 0.003). The percentage of distance lost due to the trough was 25%. Furthermore, the supination moment arm in the supinated position was significantly correlated with the tuberosity distance. CONCLUSIONS: The trough technique resulted in a significant decrease (p = 0.036) in the moment arm of a 60 degrees supinated forearm and a significant reduction (p = 0.003) in radial tuberosity height. The loss of the supination moment arm was correlated with the decrease in tuberosity height, providing evidence that the radial protuberance acts as a mechanical cam. CLINICAL RELEVANCE: The anterior protuberance of the radial tuberosity functions as a supination cam; therefore, consideration should be given to preserve its topographical anatomy during a distal biceps repair. PMID- 26677236 TI - Proximal Femoral Varus Derotation Osteotomy in Children with Cerebral Palsy: The Effect of Age, Gross Motor Function Classification System Level, and Surgeon Volume on Surgical Success. AB - BACKGROUND: The purpose of this study was to evaluate mid-term results of proximal femoral varus derotation osteotomy (VDRO) in children with cerebral palsy and determine what effect age, Gross Motor Function Classification System (GMFCS) level, and surgeon volume had on surgical success. METHODS: We analyzed a cohort of children with cerebral palsy who underwent VDRO for hip displacement at a tertiary-level pediatric hospital between 1994 and 2007. Age, sex, GMFCS level, preoperative radiographic parameters, previous botulinum toxin administration or soft-tissue release, adjunctive pelvic osteotomy, the performance of bilateral surgery at the index VDRO, and surgeon volume (the number of procedures performed) were recorded. Results were analyzed via univariate and multivariate analyses for association with the need for revision hip surgery. Kaplan-Meier survivorship curves were generated, determining the time from index surgery to failure (defined as the need for subsequent surgical procedures on the hip and/or pelvis, or a hip migration percentage of >50% at the time of final follow-up), and were further stratified according to osseous versus soft-tissue revision. RESULTS: A total of 567 VDROs were performed in 320 children (mean age [and standard deviation], 8.2 +/- 3.8 years). The mean follow-up was 8.3 years (range, three to eighteen years). Of the initial 320 patients, 117 (37%) were considered to have had failure. Multivariate Cox regression analysis confirmed that younger age at surgery (p < 0.001), increased GMFCS level (p = 0.01), and lower annual surgical hip volume (p = 0.02) were significant independent predictors of any type of surgical revision. Furthermore, soft-tissue release at VDRO was protective against revision (p = 0.02). Five-year survivorship analysis revealed a 92% success rate for children classified as GMFCS levels I and II compared with a 76% success rate for those of GMFCS level V (p < 0.01). CONCLUSIONS: This study demonstrated a 37% failure rate after VDRO in children with cerebral palsy. Older age, lower GMFCS level, and increased surgeon volume were strong predictors of surgical success. PMID- 26677237 TI - Effect of Naproxen Prophylaxis on Heterotopic Ossification Following Hip Arthroscopy: A Double-Blind Randomized Placebo-Controlled Trial. AB - BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. Our objective was to determine the effect of postoperative naproxen therapy on the development of HO following arthroscopic surgery for femoroacetabular impingement. METHODS: Between August 2011 and April 2013, 108 eligible patients were enrolled and randomized to take naproxen or a placebo for three weeks postoperatively. Radiographs were made at routine follow-up visits for one year following surgery. The primary outcome measure was the development of HO, as classified with the Brooker criteria and two-dimensional measurements on radiographs made at least seventy-five days postoperatively (average, 322 days). The primary analysis, performed with a Fisher exact test, compared the proportion of subjects with HO between the treatment and control groups. A single a priori interim analysis was planned at the midpoint of the study. RESULTS: Our data safety and monitoring board stopped this study when the interim analysis showed that the stopping criterion had been met for demonstration of efficacy of the naproxen intervention. The prevalence of HO was 46% (twenty-two of the forty eight in the final analysis) in the placebo group versus 4% (two of forty-eight) in the naproxen group (p < 0.001). Medication compliance was 69% overall, but it did not differ between the naproxen and placebo groups. Minor adverse reactions to the study medications were reported in 42% of the patients taking naproxen versus 35% of those taking the placebo (p = 0.45). CONCLUSIONS: In this trial, prophylaxis with naproxen was effective in reducing the prevalence of HO without medication-related morbidity. PMID- 26677238 TI - A Clinical Prediction Rule for Functional Outcomes in Patients Undergoing Surgery for Degenerative Cervical Myelopathy: Analysis of an International Prospective Multicenter Data Set of 757 Subjects. AB - BACKGROUND: Cervical spondylotic myelopathy (CSM) is a progressive spinal condition that is often managed surgically. Knowledge of important predictors of surgical outcome can provide decision support to surgeons and enable them to effectively manage their patients' expectations. The purpose of this study was to identify the most important clinical predictors of surgical outcome in patients with CSM using data from two multinational prospective studies. METHODS: A total of 757 patients treated surgically for CSM participated in either the CSM-North America or the CSM-International study. The model was designed to distinguish between patients who achieved a modified Japanese Orthopaedic Association (mJOA) score of >=16 at the one-year follow-up and those who did not (mJOA < 16). A score of 16 was chosen as the cutoff as an mJOA of >=16 translates to minimal impairment. Univariate analyses evaluated the relationship between outcome and various clinical predictors. Multivariate Poisson regression was used to create the final prediction rule and estimate relative risks. RESULTS: Based on univariate analyses, the probability of achieving a score of >=16 decreased with the presence of certain symptoms, including gait dysfunction, the presence of certain signs such as lower limb spasticity, positive smoking status, higher comorbidity score, more severe preoperative myelopathy, and older age. The final model consisted of six significant and clinically relevant predictors: baseline severity score (relative risk [RR], 1.11; 95% confidence interval [CI], 1.07 to 1.15), impaired gait (RR, 0.76 [ref. = absence]; 95% CI, 0.66 to 0.88), age (RR, 0.91 per decade; 95% CI, 0.85 to 0.96), comorbidity score (RR, 0.93; 95% CI, 0.88 to 0.98), smoking status (RR, 0.78 [ref. = non-smoking]; 95% CI, 0.65 to 0.93), and duration of symptoms (RR, 0.95; 95% CI, 0.90 to 0.99). CONCLUSIONS: Patients were more likely to achieve a score of >=16 (indicating minimal impairment) if they were younger, had milder preoperative myelopathy, did not smoke, had fewer and less severe comorbidities, did not present with impaired gait, and had shorter symptom duration. PMID- 26677239 TI - Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review of the Evidence. AB - BACKGROUND: The purpose of this analysis was to determine the clinical significance of injectable hyaluronic acid (HA) in the treatment of knee osteoarthritis, and to assess which trial-level factors influence the overall treatment effect of HA on pain (as measured by a VAS [visual analog scale] or the WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index]) and the WOMAC function and WOMAC stiffness subscales. METHODS: A comprehensive literature search of PubMed, EMBASE, the Physiotherapy Evidence Database, and the Cochrane Central Register of Controlled Trials was done to locate randomized controlled trials that compared HA with control treatment and had a minimum of thirty patients per subgroup. To be considered for inclusion, each article had to include VAS or WOMAC pain, WOMAC function, and/or WOMAC stiffness as outcomes because the minimal important difference (MID) has been established for these instruments. A "best-evidence" systematic review and meta-analysis of nineteen trials was performed; because of high heterogeneity among the trials, meta regression analyses were conducted to determine the influence of trial characteristics on overall HA treatment effects for pain, function, and stiffness. RESULTS: The most consistent finding was that double-blinded, sham controlled trials had much smaller treatment effects than trials that were not sufficiently blinded (p < 0.05). For double-blinded trials, the overall treatment effect was less than half of the MID for pain, function, and stiffness. Other significant associations were found for cross-linked HAs and follow-up duration. However, the effect sizes among double-blinded trials of cross-linked HAs were still less than half of the MIDs for pain and stiffness. The statistically significant effect of follow-up duration disappeared when the open-label trials were removed from the analysis. CONCLUSIONS: Meta-analysis of only the double blinded, sham-controlled trials with at least sixty patients did not show clinically important differences of HA treatment over placebo. When all literature was added to the analysis, the overall effect was greater but was biased toward stronger treatment effects because of the influence of nonblinded or improperly blinded trials. PMID- 26677240 TI - What's New in Orthopaedic Oncology. PMID- 26677241 TI - Is There Truly "No Significant Difference"? Underpowered Randomized Controlled Trials in the Orthopaedic Literature. AB - BACKGROUND: Randomized controlled trials (RCTs) are considered the gold standard in evidence-based medicine. Underpowered RCTs that describe comparative outcomes without significance are of questionable benefit. The present study hypothesizes that a substantial proportion of RCTs in the orthopaedic literature that do not note significant differences between groups are inadequately powered. METHODS: Using the ISI Web of Science database, we searched all English-language journals in the orthopaedic category for RCTs published from January 2012 to December 2013. Qualifying articles were analyzed with regard to whether the null hypothesis was rejected (a positive study) for the primary outcome or if it was not (a negative study), whether a power analysis was performed, and whether the study was adequately powered. We performed a power analysis based on the primary outcome or outcomes of interest for the studies that did not describe a power analysis. RESULTS: After inclusion and exclusion criteria were applied, 456 RCTs were selected for complete review. Of those studies, 215 (47.1%) had negative findings and 241 (52.9%) had positive findings for primary outcomes. Twenty-five studies that failed to reject the null hypothesis noted inadequate power in the study. On the basis of our own power analyses, we found an additional thirty-five negative studies without power calculations to be underpowered. Sixty (27.9%) of the 215 negative studies were underpowered. Following binary logistic regression, only the journal impact factor was a significant predictor of whether a study was underpowered. CONCLUSIONS: If an RCT lacks adequate statistical power to identify a clinically meaningful absence of a difference between groups, there is an unacceptable risk of inappropriately failing to reject the null hypothesis. The present study found that a sizable proportion of RCTs in orthopaedic surgery in which the null hypothesis is rejected are inadequately powered. Researchers should consider this when designing clinical trials, and journal editors and reviewers should be wary of underpowered RCTs when considering manuscripts for publication. PMID- 26677243 TI - The Distance from Bench to Bedside: Commentary on an article by Benjamin D. Roye, MD, MPH, et al.: "An Independent Evaluation of the Validity of a DNA-Based Prognostic Test for Adolescent Idiopathic Scoliosis". PMID- 26677244 TI - Hip Arthroscopy and Heterotopic Ossification: Is NSAID Prophylaxis Justified? Commentary on an article by James T. Beckmann, MD, MS, et al.: "Effect of Naproxen Prophylaxis on Heterotopic Ossification Following Hip Arthroscopy: A Double-Blind Randomized Placebo-Controlled Trial". PMID- 26677245 TI - Cystic Echinococcosis. AB - Echinococcosis is one of the 17 neglected tropical diseases (NTDs) recognized by the World Health Organization. The two major species of medical importance are Echinococcus granulosus and Echinococcus multilocularis. E. granulosus affects over 1 million people and is responsible for over $3 billion in expenses every year. In this minireview, we discuss aspects of the epidemiology, clinical manifestations, and diagnosis of cystic echinococcosis or cystic hydatid disease caused by E. granulosus. PMID- 26677246 TI - Impact of Variations in Test Method Parameters on In Vitro Activity of Surotomycin against Clostridium difficile and Surotomycin Quality Control Limits for Broth Microdilution and Agar Dilution Susceptibility Testing. AB - Test parameter variations were evaluated for their effects on surotomycin MICs. Calcium concentration was the only variable that influenced MICs; therefore, 50 MUg/ml (standard for lipopeptide testing) is recommended. Quality control ranges for Clostridium difficile (0.12 to 1 MUg/ml) and Eggerthella lenta (broth, 1 to 4 MUg/ml; agar, 1 to 8 MUg/ml) were approved by the Clinical and Laboratory Standards Institute based on these data. PMID- 26677247 TI - Rapid Detection of OXA-48-Producing Enterobacteriaceae by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. AB - A rapid and sensitive (100%) matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect OXA-48-type producers, using 161 previously characterized clinical isolates. Ertapenem was monitored to detect carbapenem resistance, and temocillin was included in the assay as a marker for OXA-48-producers. Structural analysis of temocillin is described. Data are obtained within 60 min. PMID- 26677248 TI - Evaluation of an Immunochromatographic Assay for Rapid Detection of Penicillin Binding Protein 2a in Human and Animal Staphylococcus intermedius Group, Staphylococcus lugdunensis, and Staphylococcus schleiferi Clinical Isolates. AB - The performance of a rapid penicillin-binding protein 2a (PBP2a) detection assay, the Alere PBP2a culture colony test, was evaluated for identification of PBP2a mediated beta-lactam resistance in human and animal clinical isolates of Staphylococcus intermedius group, Staphylococcus lugdunensis, and Staphylococcus schleiferi. The assay was sensitive and specific, with all PBP2a-negative and PBP2a-positive strains testing negative and positive, respectively. PMID- 26677249 TI - Blastocystis in Health and Disease: Are We Moving from a Clinical to a Public Health Perspective? AB - Blastocystis is a genus of common single-celled intestinal parasitic protists with an unsettled role in human health and disease. Being a stable component of intestinal microbiota, once established, the Blastocystis parasite appears more common in healthy individuals than in patients with infectious, functional, or inflammatory bowel disease. Recent data suggest that the parasite is associated with certain gut microbiota profiles and health indices. Convincing data and tools differentiating asymptomatic colonization from infection are yet to be demonstrated. Although the parasite may elicit disease under certain circumstances, the focus on Blastocystis may be shifting from a clinical to a public health perspective. PMID- 26677250 TI - Novel Single Nucleotide Polymorphism-Based Assay for Genotyping Mycobacterium avium subsp. paratuberculosis. AB - Typing of Mycobacterium avium subspecies paratuberculosis strains presents a challenge, since they are genetically monomorphic and traditional molecular techniques have limited discriminatory power. The recent advances and availability of whole-genome sequencing have extended possibilities for the characterization of Mycobacterium avium subspecies paratuberculosis, and whole genome sequencing can provide a phylogenetic context to facilitate global epidemiology studies. In this study, we developed a single nucleotide polymorphism (SNP) assay based on PCR and restriction enzyme digestion or sequencing of the amplified product. The SNP analysis was performed using genome sequence data from 133 Mycobacterium avium subspecies paratuberculosis isolates with different genotypes from 8 different host species and 17 distinct geographic regions around the world. A total of 28,402 SNPs were identified among all of the isolates. The minimum number of SNPs required to distinguish between all of the 133 genomes was 93 and between only the type C isolates was 41. To reduce the number of SNPs and PCRs required, we adopted an approach based on sequential detection of SNPs and a decision tree. By the analysis of 14 SNPs Mycobacterium avium subspecies paratuberculosis isolates can be characterized within 14 phylogenetic groups with a higher discriminatory power than mycobacterial interspersed repetitive unit-variable number tandem repeat assay and other typing methods. Continuous updating of genome sequences is needed in order to better characterize new phylogenetic groups and SNP profiles. The novel SNP assay is a discriminative, simple, reproducible method and requires only basic laboratory equipment for the large-scale global typing of Mycobacterium avium subspecies paratuberculosis isolates. PMID- 26677251 TI - Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis. AB - Currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (IA). An electronic nose (eNose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. We recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and IA have a distinct exhaled breath profile (or breathprint) that can be discriminated with an eNose. An eNose is cheap and noninvasive, and it yields results within minutes. We determined whether Aspergillus fumigatus colonization may also be detected with an eNose in cystic fibrosis (CF) patients. Exhaled breath samples of 27 CF patients were analyzed with a Cyranose 320. Culture of sputum samples defined the A. fumigatus colonization status. eNose data were classified using canonical discriminant analysis after principal component reduction. Our primary outcome was cross validated accuracy, defined as the percentage of correctly classified subjects using the leave-one-out method. The P value was calculated by the generation of 100,000 random alternative classifications. Nine of the 27 subjects were colonized by A. fumigatus. In total, 3 subjects were misclassified, resulting in a cross-validated accuracy of the Cyranose detecting IA of 89% (P = 0.004; sensitivity, 78%; specificity, 94%). Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.89. The results indicate that A. fumigatus colonization leads to a distinctive breathprint in CF patients. The present proof-of-concept data merit external validation and monitoring studies. PMID- 26677252 TI - Verification of a Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Method for Diagnostic Identification of High-Consequence Bacterial Pathogens. AB - We examined the utility of a single matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry method for the identification of security-sensitive biological agents (risk group 3 bacterial pathogens). The goal was 2-fold: to verify a method for inclusion into our scope of accreditation, and to assess the biological safety of extractions. We developed our sample flow to include a tube-based chemical extraction, followed by filtration, before processing on MALDI-TOF MS instruments in a containment level 2 laboratory. PMID- 26677253 TI - Synergy of beta-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods. AB - Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and beta-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 MUg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any beta-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 MUg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests. PMID- 26677254 TI - Optimized Use of the MALDI BioTyper System and the FilmArray BCID Panel for Direct Identification of Microbial Pathogens from Positive Blood Cultures. AB - Despite the current reliance on blood cultures (BCs), the diagnosis of bloodstream infections (BSIs) can be sped up using new technologies performed directly on positive BC bottles. Two methods (the MALDI BioTyper system and FilmArray blood culture identification [BCID] panel) are potentially applicable. In this study, we performed a large-scale clinical evaluation (1,585 microorganisms from 1,394 BSI episodes) on the combined use of the MALDI BioTyper and FilmArray BCID panel compared to a reference (culture-based) method. As a result, the causative organisms of 97.7% (1,362/1,394) of the BSIs were correctly identified by our MALDI BioTyper and FilmArray BCID-based algorithm. Specifically, 65 (5.3%) out of 1,223 monomicrobial BCs that provided incorrect or invalid identifications with the MALDI BioTyper were accurately detected by the FilmArray BCID panel; additionally, 153 (89.5%) out of 171 polymicrobial BCs achieved complete identification with the FilmArray BCID panel. Conversely, full use of the MALDI BioTyper would have resulted in the identification of only 1 causative organism in 97/171 (56.7%) of the polymicrobial cultures. By applying our diagnostic algorithm, the median time to identification was shortened (19.5 h versus 41.7 h with the reference method; P < 0.001), and the minimized use of the FilmArray BCID panel led to a significant cost savings. Twenty-six out of 31 microorganisms that could not be identified were species/genera not designed to be detected with the FilmArray BCID panel, indicating that subculture was not dispensable for a few of our BSI episodes. In summary, the fast and effective testing of BC bottles is realistically adoptable in the clinical microbiology laboratory workflow, although the usefulness of this testing for the management of BSIs remains to be established. PMID- 26677255 TI - Performance of Copan WASP for Routine Urine Microbiology. AB - This study compared a manual workup of urine clinical samples with fully automated WASPLab processing. As a first step, two different inocula (1 and 10 MUl) and different streaking patterns were compared using WASP and InoqulA BT instrumentation. Significantly more single colonies were produced with the10-MUl inoculum than with the 1-MUl inoculum, and automated streaking yielded significantly more single colonies than manual streaking on whole plates (P < 0.001). In a second step, 379 clinical urine samples were evaluated using WASP and the manual workup. Average numbers of detected morphologies, recovered species, and CFUs per milliliter of all 379 urine samples showed excellent agreement between WASPLab and the manual workup. The percentage of urine samples clinically categorized as positive or negative did not differ between the automated and manual workflow, but within the positive samples, automated processing by WASPLab resulted in the detection of more potential pathogens. In summary, the present study demonstrates that (i) the streaking pattern, i.e., primarily the number of zigzags/length of streaking lines, is critical for optimizing the number of single colonies yielded from primary cultures of urine samples; (ii) automated streaking by the WASP instrument is superior to manual streaking regarding the number of single colonies yielded (for 32.2% of the samples); and (iii) automated streaking leads to higher numbers of detected morphologies (for 47.5% of the samples), species (for 17.4% of the samples), and pathogens (for 3.4% of the samples). The results of this study point to an improved quality of microbiological analyses and laboratory reports when using automated sample processing by WASP and WASPLab. PMID- 26677256 TI - Clinical and Molecular Characterization of Invasive Heteroresistant Vancomycin Intermediate Staphylococcus aureus Infections in Korean Hospitals. AB - Invasive heteroresistant vancomycin-intermediate Staphylococcus aureus (h-VISA) isolates were identified and characterized in 10 Korean hospitals from July 2009 to June 2011. The prevalence of h-VISA infections was 3.3% (42/1,289). Most (41/42) were health care-associated infections caused by strains belonging to sequence type 5. Cases of persistent bacteremia were frequent (17/42), and 30-day mortality was high (16/40). PMID- 26677257 TI - The physical activity profiles of South Asian ethnic groups in England. AB - BACKGROUND: To identify what types of activity contribute to overall physical activity in South Asian ethnic groups and how these vary according to sex and age. We used the White British ethnic group as a comparison. METHODS: Self reported physical activity was measured in the Health Survey for England 1999 and 2004, a nationally representative, cross-sectional survey that boosted ethnic minority samples in these years. We merged the two survey years and analysed data from 19 476 adults. The proportions of total physical activity achieved through walking, housework, sports and DIY activity were calculated. We stratified by sex and age group and used analysis of variances to examine differences between ethnic groups, adjusted for the socioeconomic status. RESULTS: There was a significant difference between ethnic groups for the contributions of all physical activity domains for those aged below 55 years, with the exception of walking. In women aged 16-34 years, there was no significant difference in the contribution of walking to total physical activity (p=0.38). In the 35-54 age group, Bangladeshi males have the highest proportion of total activity from walking (30%). In those aged over 55 years, the proportion of activity from sports was the lowest in all South Asian ethnic groups for both sexes. CONCLUSIONS: UK South Asians are more active in some ways that differ, by age and sex, from White British, but are similarly active in other ways. These results can be used to develop targeted population level interventions for increasing physical activity levels in adult UK South Asian populations. PMID- 26677258 TI - Skeletal muscle contractile function predicts activity and behaviour in zebrafish. AB - Locomotion facilitates behaviour and its underlying physiological mechanisms may therefore impact behavioural phenotypes. Metabolism is often thought to modulate locomotion and behaviour, but empirical support for this suggestion is equivocal. Muscle contractile function is directly associated with locomotion. Here, we test the hypotheses that muscle mechanics determine locomotor performance and activity in zebrafish (Danio rerio) and thereby also affect risk-taking behaviour. We show that there is a mechanistic link between muscle performance and behaviour by manipulating muscle contractile properties, which caused proportional changes in critical sustained swimming performance and, in an open arena, voluntary swimming speed, the proportion of time fish were active, and the latency to move. We modelled the relationships between muscle contractile properties, swimming performance, activity and behaviour with a partial least-squares path model. The latent variable 'muscle', formed by isolated muscle force production, stress, fatigue resistance and activation and relaxation rates, had a significant positive effect on swimming performance ('swim' reflected in sustained and sprint speeds). Together, muscle and swim had a significant positive effect on activity, and explained 71.8% of variation in the distance moved, time active and maximum voluntary speed in an open field. Activity had a significant positive effect on boldness, explaining 76.0% of variation in latencies to move and to approach a novel object. Muscle contractile function determines voluntary movement and we suggest that exploration and dispersal are functions of physiological and mechanical optimisation. Boldness therefore may be partly explained by the greater likelihood of faster fish to move further and encounter novel objects and conspecifics more quickly as a result. PMID- 26677259 TI - The water channel aquaporin-1a1 facilitates movement of CO2 and ammonia in zebrafish (Danio rerio) larvae. AB - The present study tested the hypothesis that zebrafish (Danio rerio) aquaporin 1a1 (AQP1a1) serves as a multi-functional channel for the transfer of the small gaseous molecules, CO2 and ammonia, as well as water, across biological membranes. Zebrafish embryos were microinjected with a translation-blocking morpholino oligonucleotide targeted to AQP1a1. Knockdown of AQP1a1 significantly reduced rates of CO2 and ammonia excretion, as well as water fluxes, in larvae at 4 days post fertilization (dpf). Because AQP1a1 is expressed both in ionocytes present on the body surface and in red blood cells, the haemolytic agent phenylhydrazine was used to distinguish between the contributions of AQP1a1 to gas transfer in these two locations. Phenylhydrazine treatment had no effect on AQP1a1-linked excretion of CO2 or ammonia, providing evidence that AQP1a1 localized to the yolk sac epithelium, rather than red blood cell AQP1a1, is the major site of CO2 and ammonia movements. The possibility that AQP1a1 and the rhesus glycoprotein Rhcg1, which also serves as a dual CO2 and ammonia channel, act in concert to facilitate CO2 and ammonia excretion was explored. Although knockdown of each protein did not affect the abundance of mRNA and protein of the other protein under control conditions, impairment of ammonia excretion by chronic exposure to high external ammonia triggered a significant increase in the abundance of AQP1a1 mRNA and protein in 4 dpf larvae experiencing Rhcg1 knockdown. Collectively, these results suggest that AQP1a1 in zebrafish larvae facilitates the movement of CO2 and ammonia, as well as water, in a physiologically relevant fashion. PMID- 26677260 TI - Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control. AB - Schistosomiasis - a parasitic disease that affects over 200 million people across the globe - is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator-prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator-prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots. PMID- 26677261 TI - Why arboreal snakes should not be cylindrical: body shape, incline and surface roughness have interactive effects on locomotion. AB - Depending on animal size, shape, body plan and behaviour, variation in surface structure can affect the speed and ease of locomotion. The slope of branches and the roughness of bark both vary considerably, but their combined effects on the locomotion of arboreal animals are poorly understood. We used artificial branches with five inclines and five peg heights (<=40 mm) to test for interactive effects on the locomotion of three snake species with different body shapes. Unlike boa constrictors (Boa constrictor), corn snakes (Pantherophis guttatus) and brown tree snakes (Boiga irregularis) can both form ventrolateral keels, which are most pronounced in B. irregularis. Increasing peg height up to 10 mm elicited more of the lateral undulatory behaviour (sliding contact without gripping) rather than the concertina behaviour (periodic static gripping) and increased the speed of lateral undulation. Increased incline: (1) elicited more concertina locomotion, (2) decreased speed and (3) increased the threshold peg height that elicited lateral undulation. Boiga irregularis was the fastest species, and it used lateral undulation on the most surfaces, including a vertical cylinder with pegs only 1 mm high. Overall, B. constrictor was the slowest and used the most concertina locomotion, but this species climbed steep, smooth surfaces faster than P. guttatus. Our results illustrate how morphology and two different aspects of habitat structure can have interactive effects on organismal performance and behaviour. Notably, a sharper keel facilitated exploiting shorter protrusions to prevent slipping and provide propulsion, which became increasingly important as surface steepness increased. PMID- 26677262 TI - Evaluation of coagulation via thromboelastography in healthy horses administered dexamethasone. AB - Dexamethasone was administered to healthy horses daily for 7 days. Blood samples were collected at 3 time points from both treatment and non-treatment groups, and analyzed via thromboelastography (TEG). There were no significant differences in TEG parameters between treated and untreated horses, or within treatment groups over time. PMID- 26677263 TI - Sixty Years of the Indian Journal of Dermatology: An Interpretation of the Journey. PMID- 26677264 TI - Exogenous Ochronosis. AB - Exogenous ochronosis (EO) is a cutaneous disorder characterized by blue-black pigmentation resulting as a complication of long-term application of skin lightening creams containing hydroquinone but may also occur due to topical contact with phenol or resorcinol in dark-skinned individuals. It can also occur following the use of systemic antimalarials such as quinine. EO is clinically and histologically similar to its endogenous counterpart viz., alkaptonuria, which, however, exhibits systemic effects and is an inherited disorder. Dermoscopy and in vivo skin reflectance confocal microscopy are noninvasive in vivo diagnostic tools. It is very difficult to treat EO, a cosmetically disfiguring and troubling disorder with disappointing treatment options. PMID- 26677265 TI - Vitamin D Receptor Expression in Vitiligo. AB - BACKGROUND: Vitiligo is a progressive depigmenting disorder characterized by loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Vitamin D has stimulatory effects on melanocytes and acts through its nuclear Vitamin D receptor (VDR) on target cells. AIMS AND OBJECTIVES: The purpose of this study was to declare the role of Vitamin D in the pathogenesis of vitiligo. MATERIALS AND METHODS: This case-control study included 30 vitiligo patients and 30 age, gender-matched healthy controls. Blood samples were withdrawn from the study subjects, and the serum 25(OH) D level was determined by an enzyme-linked immunosorbent assay technique. Serum 25(OH) D levels were divided into: Normal or sufficient (>=30 ng/ml), insufficient (< 30-> 20ng/ml), and deficient (<=20 ng/ml) levels. Skin biopsies were obtained from the depigmented lesions and clinically normal skin of vitiligo patients and from the controls, and VDR gene expression was determined using real-time polymerase chain reaction. RESULTS: Only 10 patients with vitiligo (33.3%) had sufficient serum 25(OH) D levels (>=30 ng/ml), 12 patients (40%) had insufficient levels, and 8 patients (26.7%) had deficient levels. On the other hand, most of the controls (96.7%) had sufficient levels. The mean serum 25(OH) D level in patients was significantly decreased compared to controls (P < 0.001). The VDR-mRNA expression was also significantly decreased in lesional and nonlesional skin of patients compared to controls (P < 0.001, P < 0.001, respectively). CONCLUSION: Vitamin D deficiency influences the extent of vitiligo and could contribute to the pathogenesis of vitiligo through its immunomodulatory role and its role in melanogenesis. PMID- 26677266 TI - A Study of Correlation Between Clinical and Histopathological Findings of Erythroderma in North Bengal Population. AB - BACKGROUND: Erythroderma is a reaction pattern characterized by erythema and desquamation of 90% or more body surface area along with some metabolic alterations. MATERIALS AND METHODS: Here we studied 32 patients of erythroderma at of North Bengal Medical College for a period of 1 year to find the etiology, clinical features and histological changes. Detailed history was taken from all the patients followed by relevant biochemical investigations and histological examination. To correlate the clinical and histopathological findings chi square test was used. RESULTS: Male preponderance was present and most of them were in the 4(th) or 5(th) decade. Etiologically the patients were divided into secondary erythroderma developing over pre-existing dermatoses, and idiopathic erythroderma. Secondary erythroderma (n = 24) cases outnumbered the idiopathic cases (n = 8). Among the pre-existing dermatoses, psoriasis was found to be the most common etiologic agent. Apart from erythema the other common presenting features were scaling and itching. Histopathological categorization was possible in 59.3% cases, rest of the cases showed non-specific dermatitis. The most common histopathologic diagnosis was psoriasis (21.8% of cases). CONCLUSIONS: Our study of clinicopathological correlation of erythroderma patients among north bengal population corroborates with most of the previous studies done in other areas. As ours is a cross-sectional study in a undefined population so we could not determine the true incidence of erythroderma in north bengal population. We might have missed lymphoma as a cause of erythroderma in idiopathic cases due to lack of long follow-up, so we understand that further studies over a defined population with long follow-up is needed to determine the true incidence and causes of idiopathic erythroderma. PMID- 26677267 TI - Role of Clinical Images Based Teaching as a Supplement to Conventional Clinical Teaching in Dermatology. AB - INTRODUCTION: Clinical Dermatology is a visually oriented specialty, where visually oriented teaching is more important than it is in any other specialty. It is essential that students must have repeated exposure to common dermatological disorders in the limited hours of Dermatology clinical teaching. AIM: This study was conducted to assess the effect of clinical images based teaching as a supplement to the patient based clinical teaching in Dermatology, among final year MBBS students. METHODS: A clinical batch comprising of 19 students was chosen for the study. Apart from the routine clinical teaching sessions, clinical images based teaching was conducted. This teaching method was evaluated using a retrospective pre-post questionnaire. Students' performance was assessed using Photo Quiz and an Objective Structured Clinical Examination (OSCE). Feedback about the addition of images based class was collected from students. RESULTS: A significant improvement was observed in the self-assessment scores following images based teaching. Mean OSCE score was 6.26/10, and that of Photo Quiz was 13.6/20. CONCLUSION: This Images based Dermatology teaching has proven to be an excellent supplement to routine clinical cases based teaching. PMID- 26677268 TI - A Pilot Study: Nailing Indian Elections with the Indelible Ink Mark. AB - CONTEXT: The indelible ink that's used in our elections was developed by National Physical Laboratories (NPL), Delhi in 1962, and has been used ever since. Though formulated by NPL, it is manufactured by Mysore Paints and Varnish Ltd. owned by the Karnataka Government. Earlier, the ink mark was applied on the cuticle but with effect from February 01, 2006 the ink is applied on the voter's left index fingernail from the distal end proximally until the cuticle using an applicator. This idea of the ink mark applied during elections was used as a simple tool to measure the rate of nail growth in a busy outpatient department of a Tertiary Hospital in South India. AIMS: To assess the feasibility of using the ink mark during elections as a method of obtaining data of nail growth across the spectrum of the entire country. SUBJECTS AND METHODS: In 74 patients presenting to a hospital, the rate of nail growth was measured. The voter's mark on the left index fingernail of patients during the recent elections was used as a marker for measuring the length of the nail. RESULTS: The average rate of nail growth was 0.113 mm/day. The rate of nail growth was found to be more in females, younger individuals, pregnancy, patients on nutritional supplementation, psoriasis. CONCLUSION: This study which was conducted on 74 patients using the election ink mark successfully confirmed the possibility of using it as an efficient tool in measuring the rate of nail growth. The findings revealed the slightly higher rate of nail growth as compared to a study done by Rani et al. However, the limited sample size in this study was the major limitation. PMID- 26677270 TI - Recurrent Diffuse Neurofibroma of Nose Associated with Neurofibromatosis Type 1: A Rare Case Report with Review of Literature. AB - Diffuse neurofibroma is an unusual variant of neurofibroma with the head and neck being the common sites of involvement. It is benign in nature and spreads superficially and has many ectatic blood vessels. Histologically it is similar to conventional neurofibromas except for a few peculiar distinguishing features. We report a case of a 14-year-old boy who presented with a diffuse recurrent painless swelling over the dorsum of the nose with the clinical stigmata of neurofibromatosis. Microscopy revealed a diagnosis of diffuse neurofibroma with a few foci showing differentiation towards Meissner's type of tactile corpuscles. It is important to recognize this entity as it has a tendency to recur, yet hardly ever become malignant and is almost always associated with neurofibromatosis type 1. PMID- 26677269 TI - A Study of the Factors Associated with Risk for Development of Pressure Ulcers: A Longitudinal Analysis. AB - BACKGROUND: Pressure ulcers (PUs) are prevalent in hospitalized patients; they may cause clinical, psychological, and economic problems in these patients. Previous studies are cross-sectional, have used pooled data, or cox-regression models to assess the risk for developing PU. However, PU risk scores change over time and models that account for time varying variables are useful for cohort analysis of data. AIMS AND OBJECTIVES: The present longitudinal study was conducted to compare the risk of PU between surgical and nonsurgical patients, and to evaluate the factors associated with the development of these ulcers over a period of time. MATERIALS AND METHODS: We evaluated 290 hospitalized patients over a 4 months period. The main outcomes for our analysis were: (1) Score on the pressure risk assessment scale; and (2) the proportion of individuals who were at severe risk for developing PUs. We used random effects models for longitudinal analysis of the data. RESULTS: The mean PU score was significantly higher in the nonsurgical patients compared with surgical patients at baseline (15.23 [3.86] vs. 9.33 [4.57]; P < 0.01). About 7% of the total patients had a score of >20 at baseline and were considered as being at high-risk for PU; the proportion was significantly higher among the nonsurgical patients compared with the surgical patients (14% vs. 4%, P = 0.003). In the adjusted models, there was no difference for severe risk for PU between surgical and nonsurgical patients (odds ratios [ORs]: 0.37, 95% confidence interval [CI]: 0.01-12.80). An additional day in the ward was associated with a significantly higher likelihood of being at high-risk for PU (OR: 1.47, 95% CI: 1.16-1.86). CONCLUSION: There were no significant differences between patients who were admitted for surgery compared with those who were not. An additional day in the ward, however, is important for developing a high-risk score for PU on the monitoring scale, and these patients require active interventions. PMID- 26677271 TI - Efficacy of the Q-switched Neodymium: Yttrium Aluminum Garnet Laser in the Treatment of Blue-black Amateur and Professional Tattoos. AB - BACKGROUND: Q-switched neodymium: yttrium aluminum garnet (Nd: YAG) laser at a wavelength of 1064 nm primarily targets dermal melanin and black tattoo ink. Recent studies have shown that this laser is effective in treating black tattoos. There are few studies conducted in India for the same. AIM: The aim was to assess the effectiveness of Q-switched Nd: YAG laser (QSNYL) in the treatment of blue black tattoos following 3 treatment sessions. MATERIALS AND METHODS: This study, a prospective interventional study included a total of 12 blue-black tattoos. Following informed consent for the procedure, as well as for photographs, a questionnaire was administered, and improvement perceived by the patient was recorded. In addition, global assessment score (GAS) by a blinded physician was also recorded. Photographs were taken at baseline and at every follow-up. Each patient underwent three treatment sessions with 1064 nm QSNYL at 4-6 weekly intervals. Fluences ranged from 1.8 to 9 J/cm(2). The follow-up was done monthly for 4 months from the first treatment session. The response was assessed by patient assessment (PA) and GAS by comparing photographs. RESULTS: After three treatment sessions, although no patient achieved clearance, most patients showed good response with few adverse effects. An average of 64.1% (GAS) and 54.2% (PA) improvement was observed in 12 tattoos. Tattoos more than 10-year-old showed quicker clearing than those less than 10-year-old. Amateur tattoos also showed a better response in comparison to professional tattoos. CONCLUSION: Totally, 1064 nm QSNYL is safe and effective for lightening blue-black tattoos in pigmented Indian skin. All patients achieved near complete clearance following the continuation of treatment (an average of six sessions) although this was spaced at longer intervals. PMID- 26677272 TI - A Relationship between Physical Activities and Hand Dermatitis: An Epidemiology Study of the USA Population. AB - BACKGROUND: Hand dermatitis is a common, chronic relapsing skin disease, resulting from a variety of causes including endogenous predisposition and environmental exposures to irritants and allergens. Physical activities have been reported to be beneficial for patients with hand dermatitis. OBJECTIVES: We aim to evaluate the association between self-reported physical activities and hand dermatitis using the 2003-2004 National Health and Nutrition Examination Survey (NHANES) database. METHODS: Information regarding 2,688 participants aged 20 to 59 years from the 2003-2004 NHANES cycle were retrieved and analyzed. Diagnosis of hand dermatitis was based on standardized photographs of the hands read by two dermatologists. Physical activity during leisure time for the prior 30 days was assessed using standardized questionnaire. Based on the suggested MET scores provided for each response in the questionnaire section of the NHANES methodology, the MET scores for average level of physical activities, walking/bicycling, and performing tasks around home/yard for the past 30 days was calculated. RESULTS: There were 42 (1.56%) diagnosed cases of active hand dermatitis among the 2,688 participants. Those who reported recent vigorous or moderate physical activities were less likely to have a diagnosis of active hand dermatitis (OR: 0.436, 95% CI: 0.200 to 0.947, P = 0.036 and OR: 0.489, 95% CI: 0.261 to 0.916, P = 0.025, respectively). This negative association remained statistically significant even after adjusting for age, gender, ethnic groups and atopic diathesis. CONCLUSIONS: Moderate and vigorous levels of physical activities appeared to be beneficial for hand dermatitis. Therefore, it is important to advise patients with active hand dermatitis to remain physically active. However, clinicians should also be cognizant of the fact that the heat and sweat generated from physical activities might also exacerbate the condition. PMID- 26677273 TI - Sirolimus as Long-term Graft-versus-host-disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplant Recipients for Non-malignant Disorders is Associated with High Incidence of Acneiform Lesions. AB - BACKGROUND: Sirolimus has provided the option for calcineurin inhibitor (CNI) free immunosuppressive therapy in both solid organ transplant (SOT) and hematopoietic stem cell transplantation (HSCT). However, long-term use of sirolimus has been reported to be associated with a high incidence of cutaneous side effects in SOT, particularly acneiform lesions. MATERIALS AND METHODS: We studied the incidence of acneiform lesions and the risk factors in 41 HSCT recipients between ages 4 and 64 years, undergoing HSCT for malignant (n = 29) and non-malignant diseases (n = 12) from haploidentical family donors. RESULTS: Seven patients developed acneiform lesions at the median of 85 days (range, 45 105 days). Acneiform lesions occurred in 6/11 patients on sirolimus and in only 1/30 patients not receiving sirolimus (P = 0.001). This was more frequent in patients with non-malignant disorders (5/12 versus 2/29, P = 0.01) and those receiving graft from female donors (7/23 versus 0/18, P = 0.01). CONCLUSIONS: Despite being frequently reported in SOT, this is the first such report in HSCT. Our study suggests that prolonged use of sirolimus might be associated with high incidence of acneiform lesions in haploidentical HSCT recipients with non malignant diseases, particularly in those receiving graft from a female donor. We discuss the possible reasons for these findings and the putative mechanism of acneiform lesions in these patients. PMID- 26677274 TI - Genital/Perigenital Inflammatory Linear Verrucous Epidermal Nevus: A Case Series. AB - BACKGROUND: Inflammatory linear verrucous epidermal nevus (ILVEN) is a distinct variety of keratinocytic epidermal naevus. In contrast to non-inflammatory epidermal naevi, ILVEN are far less common, usually erythematous and intractably pruritic. ILVEN usually appears at birth or early childhood and has a linear distribution following the Blaschko lines. Genital/perigenital involvement is relatively rare. OBJECTIVES: To describe the clinical features of 9 children with ILVEN localized to the genital and perigenital areas. METHOD: A retrospective study of 9 children with ILVEN presenting to a tertiary care Dermatology Clinic between 2007 and 2014 was undertaken. The clinical and histopathological features were reviewed. RESULTS: Nine children (6 females, 3 males) were included in the study based on their characteristic clinicopathological features. The lesions were associated with severe itching in all cases. The mean age at presentation was 4 years (range 1-11 years). Onset of lesions was before 6 months of age in 8 patients. Left sided involvement was twice as common as the right sided one. Male patients had penoscrotal and groin involvement while all the female children had vulvar lesions. None of the children had any extracutaneous abnormalities. The children were treated with topical agents with variable relief or symptoms. CONCLUSIONS: The possibility of ILVEN should be considered in every linear genital lesion in children. We have presented the largest series of perigenital ILVEN reported in English literature. PMID- 26677275 TI - Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon. AB - An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon. PMID- 26677276 TI - Metastatic Fungating Ulcerative Growth on Vulva as a Presenting Feature of Carcinoma Cervix: A Rare Case Report. AB - Carcinoma of the cervix is the second to fourth most common malignancy in women. It metastasizes most often to the lungs, bones, and liver. Skin involvement originating from cervical cancer is rare, even in the terminal stages of the disease. Cutaneous metastasis of cervical cancer usually presents as cutaneous nodules, papules/plaques, maculopapular rash, and diffuse inflammatory rash. We report a rare case (only the second reported case to the best of our knowledge) of a 50-year-old woman with cutaneous metastasis in form of fungating ulcerative growth on mons pubis as presenting feature of carcinoma cervix. PMID- 26677277 TI - Rediscovering Perifollicular Elastolysis: A Hitherto Undocumented Entity in India. AB - Perifollicular elastolysis, also known as papular acne scars is a common but taken for granted entity. It appears as asymptomatic whitish yellow papules on the trunk and proximal arms. Histologically there is loss of elastin around the pilosebaceous follicles. The lesions are the result of a scarring process that appear as papules and are often mistaken for papules of acne and are treated. A knowledge of this entity which has never been described before in India is being reiterated. PMID- 26677278 TI - Malignant Melanoma Clinically Masquerading Vascular Tumor: A Diagnostic Dilemma. AB - Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent. PMID- 26677279 TI - Acral, Superficial Spreading Melanoma Arising on Melanocytic Nevus in a Pregnant Woman: A Case Report with Review. AB - We are reporting a case of superficial spreading melanoma (SSM) on left palm of a 37-year-old pregnant housewife. She had a small acquired melanocytic nevus on her left palm since childhood, which changed its consistency and color in the last 4 months. Dermoscopy of the lesion indicated malignant changes. The lesion was managed surgically using split-thickness skin graft. The histopathology report was suggestive of SSM with positive HMB-45 cells. SSM is very rare on the acral site, and it is very difficult to differentiate it from acral lentiginous melanoma. The rarity of the site (acral nonchronic sun damage) with evolution during pregnancy and importance of management approach are reasons for publishing this case. PMID- 26677280 TI - Dermatitis Artefacta: A Review of Five Cases: A Diagnostic and Therapeutic Challenge. AB - Dermatitis artefacta (DA) is a self-inflicted dermatological condition where the underlying motive is to assume a sick role. The act of self-harm is to discharge the inner sense of isolation and emotional distress, which is too great to endure. We, hereby, report five interesting cases of DA with varied presentations, using diverse and innovative means for inflicting injury/injuries. Rarity may be attributed to masquerading presentation, leading to misdiagnosis and paucity of awareness among the physicians. Lack of proper identification of the underlying psychiatric disturbances may be the major cause of the loss of follow-ups. Here, we were fortunate enough to identify the emotional need of most of the patients. A flexible, nonconfrontational yet strong therapeutic rapport is required to improve the therapeutic outcomes. PMID- 26677281 TI - Unilateral, Linear Blue Rubber Bleb Nevus Syndrome (Bean's syndrome): An Unfamiliar Presentation: First Case from India. AB - Blue rubber bleb nevus syndrome (BRBNS) also called Bean's syndrome is a rare disorder characterized by multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the gastrointestinal tract. We report here, a 21-year-old woman patient, who presented with unilateral, blaschkoid distribution of cutaneous venous malformations along with blue rubber bleb nevus and recurrent episodes of hematochezia due to vascular lesions in the sigmoid colon; likely to be a case of BRBNS. The unusual unilateral, blaschkoid distribution of BRBNS prompted this present report. PMID- 26677282 TI - Holotranscobalamin and MethylMalonic Acid as the Diagnostic Tool for Vitamin B12 Deficiency. PMID- 26677283 TI - Author Reply. PMID- 26677284 TI - Aquired Ectopic Nail or Onychoheterotopia. PMID- 26677285 TI - Allergic Contact Dermatitis to Walnut (Juglans Regia) Husk. PMID- 26677286 TI - Subungual Keratoacanthoma. PMID- 26677287 TI - Acute Hemorrhagic Edema of Infancy. PMID- 26677288 TI - Onychomadesis Following Varicella Infection: Is it a Mere Co-incidence? PMID- 26677289 TI - Multifocal Cutaneous Granular Cell Tumor: An Uncommon Clinical Entity. PMID- 26677290 TI - 23(rd) World Congress of Dermatology, Vancouver, Canada, June 8-13, 2015. PMID- 26677291 TI - Recurrent Bleeding and Bruising Over Little Finger: A Diagnostic Conundrum! PMID- 26677292 TI - Plasma Levels of Interleukin-17, Interleukin-23, and Transforming Growth Factor beta in Sudanese Patients with Vitiligo: A Case-Control Study. AB - BACKGROUND: Vitiligo is the most common pigmentary skin disorder. It is a multifactorial polygenic disease with epidermal melanocyte destruction. The cytokines profile found in vitiliginous patients was not fully elucidated. AIMS: We sought to assess the autoimmune nature of vitiligo by comparing plasma levels of interleukin (IL)-17, IL-23, and transforming growth factor beta (TGF-beta) in adult Sudanese vitiligo patients with matched control individuals. SUBJECTS AND METHODS: Case-control study was conducted in Khartoum Dermatologic Teaching Hospital, in the period between July and December 2013. The cases were 42 adult Sudanese vitiligo patients matched with 43 control individuals. The cytokines were measured in the plasma by the quantitative "sandwich" ELISA. RESULTS: Patients showed a significant lower median (25-75(th) inter-quartile) of TGF-beta than control (0.042 [0.041-0.044] vs. 0.047 [0.042-0.049]; P <= 0.001). Both IL 17 and IL-23 showed no significant difference between cases and controls. IL-17 showed a significant inverse relationship when correlated with TGF-beta (r = 0.24; P = 0.026) while showing direct relationship when correlated with age (r = 0.28; P = 0.009). CONCLUSION: The positive findings detected in this study coincide with the important immunoregulatory role of the TGF-beta, and support the autoimmune nature of the disease. PMID- 26677293 TI - Psychological Morbidity Among Dermatological Patients in a Rural Setting. AB - BACKGROUND: Dermatological conditions have an impact on psychology of the patients. There is a dearth of studies regarding this field in Rural population of India. AIMS AND OBJECTIVES: The primary objective of this study is to evaluate the psychiatric morbidity in patients affected with Dermatological condition in a rural population and secondary objective is to assess the morbidity in dimensions of Depression Severity and the quality of life in the Emotional Sphere, Physical Symptoms, Psychosocial Functioning. SUBJECTS AND METHODS: Seventy three rural patients were included in the study. PHQ9 and SKINDEX-29 was used to assess the psychiatric morbidity and quality of life. Statistical analysis was done using SPSS V 20. Chi-square test was used as a test of significance. RESULTS: Significance has been found for duration of suffering from a dermatological condition and quality of life (p=0.03). Correlation has also been established between dermatological diagnosis with depression severity (p=0.004) or quality of life (p=0.004). In the sub scales of SKINDEX it was noted that overall dysfunction was notably more marked in Emotional Sphere and Psychosocial Functions than the Physical symptoms. Eczema was the most affected diagnosis in Skindex indicating a poor quality of life followed by psoriasis, Acne vulgaris and Seborrhoeic Dermatitis however, It was found that the majorly affected condition in depression severity was Psoriasis followed by Eczema, Acne Vulgaris and Seborrhoeic Dermatitis. CONCLUSION: There seems to be an increased morbidity among the rural population in depression severity and that of quality of life in terms of emotional sphere and psychosocial functioning. PMID- 26677294 TI - Knowledge and Attitude of Medical Resident Doctors Toward Antihistamines. AB - BACKGROUND: Allergic rhinitis and urticaria are chronic persistent allergic conditions that need proper management as they significantly reduce quality of life measures. Of the many pharmacological options of allergic rhinitis and urticaria, second-generation antihistamines are the mainstay of therapy. AIMS: This review focuses on the knowledge of medical residents toward prescribing antihistamines, according to the new ARIA and GA2LEN guidelines for allergic rhinitis and urticaria, attempting to find the cause of less prescription of newer second-generation antihistamines by finding out the knowledge and attitude of the doctors prescribing them to the patients. MATERIALS AND METHODS: The study was carried out among resident doctors at a tertiary care teaching hospital. Primary data from 100 resident doctors, who gave their informed consent, was collected. A prevalidated questionnaire regarding knowledge, attitude and prescribing practice of antihistamines was filled up. The data was then analyzed with suitable statistical tests. Every question was first validated using the Chi square test, and significance was below 10% hence proving validity of the questions. RESULTS: Out of the doctors surveyed, 82% of doctors said they prescribed second-generation antihistamines, while 18% still prescribed first generation antihistamines. Out of the 82% that prescribed second-generation antihistamines, 8.9% also prescribed first-generation antihistamines as well. 23% of doctors surveyed had heard about the ARIA and GAL2EN guidelines and their recommendations for prescribing second-generation antihistamines over the older first-generation antihistamines, while 77% of them had not heard of these position papers. CONCLUSION: First-generation or classic antihistamines are still overused due to the lack of knowledge of various guidelines that have been published. The main reason for not prescribing the second-generation antihistamines was due to the increased cost per tablet compared to the more economical first-generation antihistamines. PMID- 26677295 TI - The Association between Atopic Disorders and Keloids: A Case-control Study. AB - BACKGROUND: Keloids and atopic disorders share common inducing and maintaining inflammatory pathways that are characterized by T-helper cell 2 cytokines. AIMS AND OBJECTIVES: The objective of this study was to test for associations between keloids and atopic eczema, asthma and hay fever. MATERIALS AND METHODS: This was a case-control study with 131 patients diagnosed with keloids at our dermatology outpatient clinic between 2000 and 2012. Controls were 258 partners of keloid or sarcoidosis patients. Patient who reported life time prevalences of atopic eczema, asthma and hay fever were assessed using a questionnaire based on The European Community Respiratory Health Survey (ECRHS) and The International Study of Asthma and Allergies in Children (ISAAC). RESULTS: The prevalence of asthma was lower in keloid patients (19/131 vs. 20/258, P = 0.035), as was being diagnosed with asthma by a physician (18/131 vs. 19/258, P = 0.039) and using inhalators for asthma (13/131 vs. 7/258, P = 0.02). After adjusting for age and non-European descent the odds ratio for having a keloid was (adjusted OR = 4.44; 95% CI 1.59-12.40) in asthmatics using inhalators. There were no clear and consistent associations found for keloids with atopic eczema or with hay fever. CONCLUSION: In conclusion, our study shows that keloids may be strongly associated with atopic asthma. Atopic eczema and hay fever do not seem to be correlated with keloid. Further studies are warranted to assess the validity of atopic asthma as a risk factor for the development of keloid scars. PMID- 26677297 TI - Dyschromias: A Series of Five Interesting Cases from India. AB - Dyschromatosis is a pigmentary genodermatosis which presents with hyper and hypopigmented skin lesions giving a mottled appearance. It is a rare entity in India reported mainly in the East Asian population. Classically, two forms have been described; dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria. Here we report four cases of DUH and one case of dyschromatosis symmetrica hereditaria from India. PMID- 26677298 TI - Molluscoid Pseudovesicles: An Unusual Presentation of Sweet's Syndrome. AB - Sweet's syndrome is a well-known entity in the field of dermatology. It has presented itself in myriad forms, well-recorded in literature. Our patient presented with a sudden eruption of nontender molluscoid pseudovesicles distributed over the neck and forearms alone. A complete diagnostic work up for the same did not give any clue regarding an underlying systemic ailment, responsible for the dermatosis. This case is being presented because of this extremely rare morphology of Gomm-Button disease. PMID- 26677296 TI - A Clinico-Etiological Study of Dermatoses in Pediatric Age Group in Tertiary Health Care Center in South Gujarat Region. AB - BACKGROUND: Dermatologic conditions have different presentation and management in pediatric age group from that in adult; this to be studied separately for statistical and population based analysis. OBJECTIVE: To study the pattern of various dermatoses in infants and children in tertiary health care center in South Gujarat region. MATERIALS AND METHODS: This is a prospective study; various dermatoses were studied in pediatric patients up to 14 years of age attending the Dermatology OPD of New Civil Hospital, Surat, Gujarat over a period of 12 months from June 2009 to June 2010. All patients were divided into four different study groups: <1 month (neonates), 1 month to 1 year, >1 to 6 years and 7 to 14 years. RESULTS: There were 596 boys and 425 girls in total 1021 study populations. Majority of the skin conditions in neonates were erythema toxicum neonatorum (12.97%), scabies (9.92%), mongolian spot (9.16%), and seborrheic dermatitis (7.63%). In > 1 month to 14 years age group of children among infectious disorder, children were found to be affected most by scabies (24.49%), impetigo (5.96%), pyoderma (5.62%), molluscum contagiosum (5.39%), tinea capitis (4.49%), leprosy (2.02%), and viral warts (1.35%) while among non-infectious disorders, they were affected by atopic dermatitis (4.27%), pityriasis alba (4.16%), seborrheic dermatitis (3.60%), pityriasis rosea (3.15%), others (3.01%), phrynoderma (2.70%), lichen planus (2.58%), contact dermatitis (1.57%) and ichthyosis (1.45%). CONCLUSION: There is a need to emphasize on training the management of common pediatric dermatoses to dermatologists, general practitioners and pediatricians for early treatment. PMID- 26677299 TI - Leukemia Cutis: An Unusual Presentation of Acute Lymphoblastic Leukemia in a Child. AB - Leukemia cutis (LC) is a nonspecific word used for cutaneous infiltration of leukemia, which is a rare presentation of acute lymphoblastic leukemia (ALL), and always a harbinger of poor prognosis. We report a case of LC in a 5-year-old boy with a past medical history of ALL (L1) presented with multiple asymptomatic oval or annular red patches and plaques on his thighs, buttocks and back waist, and part of them were scaling lesions. A biopsy was performed and histopathological examination showed that medium-sized atypical cells with round to oval contours, scant cytoplasm, and finely dispersed chromatin infiltrated into the dermis and subcutis, and the perivascular and periadnexal areas were involved. Immunophenotyping showed that the atypical cells were positive for CD45, CD3epsilon, CD99, and Ki67 (about 70%). Considering the patient's medical history and the histopathology, the patient was diagnosed with LC. PMID- 26677300 TI - Under-reported Finding in Acral Erythema Multiforme. AB - Erythema multiforme is an acute muco-cutaneous hypersensitivity reaction with a variety of etiologies. It is characterized by a skin eruption, with or without oral or other mucous membrane lesions. General characteristics and treatmet have been described, but nail findings are rarely reported Here we present a 26-year old patient with acral erythema multiforme and erythronychia adjacent to skin lesions on the back of the hands. To our knowledge this association had not been reported before. PMID- 26677301 TI - Multiple Granuloma Annulare in a 2-year-old Child. AB - Granuloma annulare is a benign, self-limiting, inflammatory and granulomatous disease of unknown etiology occurring in both adults and children. An 18-month old male child had multiple progressive annular plaques over the lower extremities. Clinical and histopathological features were consistent with granuloma annulare. Localized granuloma annulare is the most common form in children. We report a young child with multiple, progressive granuloma annulare over the lower extremities. PMID- 26677302 TI - Basal Cell Carcinoma and Syringocystadenoma Papilliferum Arising in Nevus Sebaceous on Face-A Rare Entity. AB - Nevus sebaceus of Jadassohn is a congenital cutaneous hamartoma comprising of multiple skin structures. It has the potential to develop into variety of neoplasms of various epidermal adnexal origins. While multiple tumors may occasionally arise, it is unusual to develop two different types of tumor, benign and malignant, to arise simultaneously within a single sebaceus nevus. Here in, we report a case of a 27-year-old male with two neoplastic proliferations including a syringocystadenoma papilliferum a benign tumor and basal cell carcinoma a malignant tumor arising in a long-standing nevus sebaceus on the face. Neoplastic changes are common in nevus sebaceous present on scalp but our case is unique due to the presence of two different types of neoplasm in a nevus sebaceous which was present on face. PMID- 26677303 TI - Congenital Giant Keratinous Cyst Mimicking Lipoma: Case Report and Review. AB - Epidermal cysts represent the most common cutaneous cysts. They arise following a localized inflammation of the hair follicle and occasionally after the implantation of the epithelium, following a trauma or surgery. Conventional epidermal cysts are about 5 cm in diameter; however, rare reports of cysts more than 5 cm are reported in the literature and are referred as "Giant epidermal cysts." Epidermal cysts although common, can mimic other common benign lesions in the head and neck area. A thorough clinico-pathologic investigation is needed to diagnose these cutaneous lesions as they differ in their biologic behavior, treatment, and prognosis. We report a case of a giant epidermoid cyst in the scalp area of a young female patient which mimicked lipoma on clinical, as well as cyotological examination. We also present a brief review of epidermal cysts, their histopathological differential diagnosis, and their malignant transformation. PMID- 26677304 TI - Allergic Contact Dermatitis to Eye Drops. AB - Allergic contact dermatitis (ACD) occurs due to a milieu of allergens and involves different anatomical sites, including eyelids, and periorbital areas. Topically applied ophthalmic drugs are a potential cause of ACD of the periorbital region. Here we describe the report of a patient who developed ACD to eye drop preparations. PMID- 26677305 TI - Cutaneous Metastasis from Signet-ring Gastric Adenocarcinoma in a Carcinoma En Cuirasse Pattern: An Unusual Clinical-diagnostic Sequence. AB - Cutaneous metastasis (CM) of gastric adenocarcinoma (ADC) is rare and usually presents late in the course of the disease. We report a rare case of carcinoma en cuirasse (CEC) pattern of CM secondary to gastric malignancy in a 55-year-old male patient-the interesting part being that CM was the first-presenting sign, which on further histopathological and immunohistochemical evaluation led to the diagnosis of hidden gastric carcinoma. The finding of signet ring cells (SRCs) on cutaneous biopsy further added a differential of the rare possibility of primary cutaneous tumors. PMID- 26677306 TI - Purpura Fulminans Due to Acquired Protein C Deficiency. AB - Purpura fulminans (PF) may be the presenting symptom in a patient with protein C (PC) deficiency. It is a hematological emergency and presents with extensive areas of hemorrhagic necrosis of the skin. PC deficiency is usually genetically inherited. However, we report a 1 year and 4 months boy, who presented with acquired PC deficiency possibly of postinfectious etiology and developed PF. PMID- 26677307 TI - Lupus Erythematosus Panniculitis in Pregnancy. AB - A case of lupus erythematosus (LE) panniculitis in pregnancy without any lesions of discoid LE or systemic LE is being reported. There were no systemic symptoms. Her ANA, anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies were within normal limits. Diagnosis of lupus panniculitis was considered on clinical and histopathological grounds. The condition responded favorably to systemic steroid therapy. PMID- 26677308 TI - Faun Tail Overlying Spinal Dysraphism (Diastematomyelia) at the Mid Thoracic Level: Cosmetic Improvement Achieved with Diode Laser Epilation. PMID- 26677309 TI - Subcutaneous Sarcoidal Granuloma Underlying Superficial Basal Cell Carcinoma. PMID- 26677310 TI - Feasibility and Utility of the Fric Test in Symptomatic Dermographism: A Pilot Study. PMID- 26677311 TI - A Probable Case of Chlorpromazine-induced Lichenoid Eruptions Initially Involved Palmoplantar Areas. PMID- 26677312 TI - Arciform Eruptions of Trisomy 21. PMID- 26677313 TI - An Uncommon Disease at an Unusual Site in a Female Child. PMID- 26677314 TI - Development of an endoluminal high-intensity ultrasound applicator for image guided thermal therapy of pancreatic tumors. AB - An ultrasound applicator for endoluminal thermal therapy of pancreatic tumors has been introduced and evaluated through acoustic/biothermal simulations and ex vivo experimental investigations. Endoluminal therapeutic ultrasound constitutes a minimally invinvasive conformal therapy and is compatible with ultrasound or MR based image guidance. The applicator would be placed in the stomach or duodenal lumen, and sonication would be performed through the luminal wall into the tumor, with concurrent water cooling of the wall tissue to prevent its thermal injury. A finite-element (FEM) 3D acoustic and biothermal model was implemented for theoretical analysis of the approach. Parametric studies over transducer geometries and frequencies revealed that operating frequencies within 1-3 MHz maximize penetration depth and lesion volume while sparing damage to the luminal wall. Patient-specific FEM models of pancreatic head tumors were generated and used to assess the feasibility of performing endoluminal ultrasound thermal ablation and hyperthermia of pancreatic tumors. Results indicated over 80% of the volume of small tumors (~2 cm diameter) within 35 mm of the duodenum could be safely ablated in under 30 minutes or elevated to hyperthermic temperatures at steady-state. Approximately 60% of a large tumor (~5 cm diameter) model could be safely ablated by considering multiple positions of the applicator along the length of the duodenum to increase coverage. Prototype applicators containing two 3.2 MHz planar transducers were fabricated and evaluated in ex vivo porcine carcass heating experiments under MR temperature imaging (MRTI) guidance. The applicator was positioned in the stomach adjacent to the pancreas, and sonications were performed for 10 min at 5 W/cm2 applied intensity. MRTI indicated over 40 degrees C temperature rise in pancreatic tissue with heating penetration extending 3 cm from the luminal wall. PMID- 26677315 TI - Identification of covalent active site inhibitors of dengue virus protease. AB - Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and protease-inhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described. PMID- 26677316 TI - Phase II trial of docetaxel combined with nedaplatin for patients with recurrent and metastatic nasopharyngeal carcinoma. AB - PURPOSE: This Phase II trial was designed to evaluate the efficacy and safety of docetaxel combined with nedaplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. METHODS: In this multicenter Phase II trial, the patients were treated with intravenous docetaxel (75 mg/m(2), day 1) and nedaplatin (80 mg/m(2), day 1), each cycle repeated every 3 weeks for two cycles at least. RESULTS: From January 2010 to November 2013, a total of 78 patients were recruited in this trial. Among them, 73 patients were assessable for response. The treatment was well tolerated. The main hematological adverse event was neutropenia. A total of 12 patients (15.4%) had grade 3 or grade 4 neutropenia. Grade 3 anemia was observed in six patients (7.7%) and no grade 3/4 thrombocytopenia was observed. No Grade 3/4 non-hematological toxicity was observed. There were five complete response (6.8%), 43 partial responses (58.9%), and the overall response rate was 65.8% (95% confidence interval [CI], 48.7% 81.2%). With a median follow-up period of 18.6 months, the median time to progression was 7.9 months (95% CI, 4.2-10.8 months), median overall survival was 15.7 months (95% CI, 11.6-18.5 months). CONCLUSION: Docetaxel combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile as first-line chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma. PMID- 26677317 TI - Patient-reported adverse drug reactions and their influence on adherence and quality of life of chronic myeloid leukemia patients on per oral tyrosine kinase inhibitor treatment. AB - PURPOSE: To evaluate adverse drug reactions (ADRs) experienced by chronic myeloid leukemia (CML) patients during per oral tyrosine kinase inhibitor (TKI) treatment and correlation of ADR symptoms with medication adherence and perceived quality of life (QoL). PATIENTS AND METHODS: Eighty-six adult, chronic-phase CML patients who had been on TKI treatment (79% on imatinib, 10.5% dasatinib, and 10.5% nilotinib) for at least 6 months participated in the study (mean age: 57.8 years, 52% males). The mean time from diagnosis was 5.1 years. All patients were interviewed, and patient-reported ADRs were obtained using a structured list. Adherence was assessed using Morisky's 8-item Medication Adherence Scale (MMAS). The symptoms' interference with patient's daily QoL was measured by asking patients about the influence of symptom(s) on their mood, general condition, enjoyment of life, walking, relationships, and work. RESULTS: Ninety-seven percent of the patients were suffering from at least one ADR. The mean number of different symptoms was seven (range: 0-15, median 6). The most commonly perceived ADRs were muscle soreness or cramp (69/86, 80%); swelling of hands, legs, feet, or around the eyes (59/86, 69%); and fatigue (43/86, 50%). No correlation was found between adherence and ADRs, because symptoms were equally common in each MMAS adherence class. Half of the patients felt that the ADRs had a negative influence on their daily QoL. A quarter of the patients reported that ADRs affected either their mood, general condition, or enjoyment of life. The incidence of almost all ADRs was much higher among patients reporting negative influence of ADRs on their daily life compared to total study population (P=0.016). CONCLUSION: TKI-related ADRs were common among CML patients irrespective of patient's adherence level. Patients who reported that ADRs had a negative influence on their daily QoL perceived more ADRs than those who did not experience a negative influence. PMID- 26677318 TI - Resistance training might have improved insulin resistance by attenuating sarcopenia. PMID- 26677319 TI - Skin diseases among elderly inhabitants of Bialystok, Poland. AB - PURPOSE: The aim of the study was to assess the most frequent skin diseases in people over 60 years old among residents of a public nursing home and students of the University of the Third Age in Bialystok. SUBJECTS AND METHODS: The study was carried out from April to June 2015 in Bialystok, in two groups: 100 residents of a public nursing home and 100 participants of the University of the Third Age, aged over 60 years, using a method of diagnostic survey with the authors' anonymous questionnaire. RESULTS: A total of 30.5% of respondents (n=61) had been treated due to skin diseases, most frequently for 6-10 years (26.2%). Fungal infection, psoriasis, and atopic dermatitis were the most frequent dermatological diseases among the study elderly. The sites affected most frequently with these diseases were upper and lower extremities and the face. A majority of the examined (63.9%) visited a dermatologist, but only when it was necessary. CONCLUSION: Skin diseases constitute a significant health problem among seniors. The elderly should be educated about healthy lifestyle, preventing the development of fungal infections. It is necessary to encourage seniors to visit dermatologists, seeking professional advice. PMID- 26677320 TI - Ethnicity and culture: is it associated with falls? PMID- 26677321 TI - Highly efficient mesenchymal stem cell proliferation on poly-epsilon-caprolactone nanofibers with embedded magnetic nanoparticles. AB - In this study, we have developed a combined approach to accelerate the proliferation of mesenchymal stem cells (MSCs) in vitro, using a new nanofibrous scaffold made by needleless electrospinning from a mixture of poly-epsilon caprolactone and magnetic particles. The biological characteristics of porcine MSCs were investigated while cultured in vitro on composite scaffold enriched with magnetic nanoparticles. Our data indicate that due to the synergic effect of the poly-epsilon-caprolactone nanofibers and magnetic particles, cellular adhesion and proliferation of MSCs is enhanced and osteogenic differentiation is supported. The cellular and physical attributes make this new scaffold very promising for the acceleration of efficient MSC proliferation and regeneration of hard tissues. PMID- 26677322 TI - Nanomedicine concepts in the general medical curriculum: initiating a discussion. AB - Various applications of nanoscale science to the field of medicine have resulted in the ongoing development of the subfield of nanomedicine. Within the past several years, there has been a concurrent proliferation of academic journals, textbooks, and other professional literature addressing fundamental basic science research and seminal clinical developments in nanomedicine. Additionally, there is now broad consensus among medical researchers and practitioners that along with personalized medicine and regenerative medicine, nanomedicine is likely to revolutionize our definitions of what constitutes human disease and its treatment. In light of these developments, incorporation of key nanomedicine concepts into the general medical curriculum ought to be considered. Here, I offer for consideration five key nanomedicine concepts, along with suggestions regarding the manner in which they might be incorporated effectively into the general medical curriculum. Related curricular issues and implications for medical education also are presented. PMID- 26677323 TI - Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon-bone interface healing for anterior cruciate ligament reconstruction. AB - Hamstring tendon autograft is a routine graft for anterior cruciate ligament (ACL) reconstruction. However, ways of improving the healing between the tendon and bone is often overlooked in clinical practice. This issue can be addressed by using a biomimetic scaffold. Herein, a biomimetic nanofiber membrane of polycaprolactone/nanohydroxyapatite/collagen (PCL/nHAp/Col) is fabricated that mimics the composition of native bone tissue for promoting tendon-bone healing. This membrane has good cytocompatibility, allowing for osteoblast cell adhesion and growth and bone formation. As a result, MC3T3 cells reveal a higher mineralization level in PCL/nHAp/Col membrane compared with PCL membrane alone. Further in vivo studies in ACL reconstruction in a rabbit model shows that PCL/nHAp/Col-wrapped tendon may afford superior tissue integration to nonwrapped tendon in the interface between the tendon and host bone as well as improved mechanical strength. This study shows that PCL/nHAp/Col nanofiber membrane wrapping of autologous tendon is effective for improving tendon healing with host bone in ACL reconstruction. PMID- 26677324 TI - Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma burdened nude mice. AB - PURPOSE: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17 demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. METHODS: CD90(+) LCSCs were isolated by magnetic-activated cell sorting from BEL 7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90 targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17 AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90(+) LCSCs and the effect of CD90@17-AAG/TMs mediated heat sensitivity were examined in vitro and in vivo. RESULTS: CD90(+) LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9+/ 7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90(+) LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90(+) LCSCs to magnetic hyperthermia. CONCLUSION: The inhibition of HSP90 could sensitize CD90(+) LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo. PMID- 26677325 TI - pH-responsive glycol chitosan-cross-linked carboxymethyl-beta-cyclodextrin nanoparticles for controlled release of anticancer drugs. AB - Carboxymethyl-beta-cyclodextrin (CMbeta-CD)-modified glycol chitosan (GCS) nanoparticles (GCS-CMbeta-CD NPs) were synthesized, and their pH-sensitive drug release properties were investigated. GCS-CMbeta-CD NPs could encapsulate doxorubicin hydrochloride (DOX), and the encapsulation efficiency and loading capacity increased with the amount of CMbeta-CD. Drug-release studies indicate that DOX released was greater in acidic medium (pH 5.0) than in weakly basic medium (pH 7.4). The mechanism underlying the pH-sensitive properties of the carrier was analyzed. Finally, the MCF-7 (human breast cancer) and SW480 cell lines (human colon cancer) were used to evaluate the cytotoxicity of the NPs. The drug-loaded carriers show good inhibition of the growth of cancer cells compared with free DOX, and the carriers have good biocompatibility. In addition, the drug loaded NPs have sustained drug-release properties. All these properties of the newly synthesized GCS-CMbeta-CD NPs suggest a promising potential as an effective anticancer drug-delivery system for controlled drug release. PMID- 26677326 TI - Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles. AB - The purpose of this study was to assess the effect of various formulation parameters on anti-CD205 antibody decorated poly(d, l-lactide co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to target dendritic cells (DCs). In brief, emulsification solvent evaporation technique was adapted to design NP formulations using two different viscosity grades (low and high) of both ester and carboxylic acid terminated PLGA. Incorporation of ligand was achieved following physical adsorption or chemical conjugation processes. The physicochemical characterizations of formulations were executed to assess the effects of different solvents (chloroform and ethyl acetate), stabilizer percentage, polymer types, polymer viscosities, ligand-NP bonding types, cross linkers, and cryoprotectants (sucrose and trehalose). Modification of any of these parameters shows significant improvement of physicochemical properties of NPs. Ethyl acetate was the solvent of choice for the formulations to ensure better emulsion formation. Infrared spectroscopy confirmed the presence of anti CD205 antibody in the NP formulation. Finally, cytotoxicity assay confirmed the safety profile of the NPs for DCs. Thus, ligand modified structurally concealed PLGA NPs is a promising delivery tool for targeting DCs in vivo. PMID- 26677328 TI - Severe arrhythmia induced by orally disintegrating aripiprazole tablets (Bosiqing((r))): a case report. AB - Psychotropic medications have been known to cause cardiac conduction disturbances. Not much is known about the cardiovascular side effects of newer atypical antipsychotics such as aripiprazole. A case of a 13-year-old girl with schizophrenia is presented. An analysis of the presented patient's clinical history indicates the need for a detailed analysis of the severe arrhythmia induced by aripiprazole. This presented case report contains valuable guidelines that can be of assistance in the treatment of patients with aripiprazole. PMID- 26677327 TI - Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma treated titanium. AB - Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium's osseointegration involves inducing bio-mimetic nanotopography to enhance cell-implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC) attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications. PMID- 26677329 TI - Stress and its association with working efficiency of junior doctors during three postgraduate residency training programs. AB - BACKGROUND: The residency training period in the medical profession is well known for physical and mental stress, which may affect cognitive function and practical life. The aims of this study were to assess prevalence of stress among the resident trainees of the three medical specialties of Saudi Commission for Health Specialties (SCHS) training programs, namely, Internal Medicine, Emergency Medicine, Family Medicine, and their association with training years, sex, and marital status. This study also aimed to correlate the stress levels with the working efficiency and self-perceived general health problems. PARTICIPANTS AND METHODS: Resident trainee physicians of SCHS were invited to complete a stress inventory Kessler 10, which is used for stress measurement. Pearson's chi-square test (chi (2)) and odds ratios (ORs) were used to quantify the associations between categorical variables. A P-value of <0.05 was considered statistically significant. RESULTS: A total of 318 (out of 389, with the response rate of 82%) resident trainees participated in this study. The mean (+/- standard deviation) age of the study population was 27.9 (+/-1.6) years. The results showed 70.4% of resident trainees had stressful conditions, which consisted of severe stress: 22.6%, moderate stress: 20.4%, and mild stress: 27.4%. During the 1st year (R-1), moderate stress (OR =5.87; 95% confidence interval =2.93-17.79; P=0.001) and severe stress (OR =11.15; 95% confidence interval =4.35-28.51; P=0.0001) levels were quite high. The highest stress level was found in Emergency Medicine (80.5%), followed by Internal Medicine (73.6%), and Family Medicine (63.2%) (chi (2)=6.42; P=0.04). The stress level decreased with the increase of years of training in Emergency Medicine (chi (2)=23.76; P<0.0001) and Internal Medicine (chi (2)=60.12; P<0.0001), whereas increased in Family Medicine (chi (2)=11.80; P=0.008). High stress level was significantly associated with absence from duty days (chi (2)=28.48, P<0.0001), inefficient day activities (chi (2)=39.15; P<0.0001), and general health problems (chi (2)=45.27; P<0.0001) of resident trainees. CONCLUSION: We found significantly high levels of stress among the resident trainees of SCHS. High levels of stress may have an effect on their working efficiency and general physical health. The high stress level decreased efficient day activity and made the trainees absent from the workplace. PMID- 26677330 TI - Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study. AB - BACKGROUND: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood. METHODS: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a >=50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs), moderate-to severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines. RESULTS: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10). Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031) and interleukin-8 (Z=-2.616; P=0.009) were significantly higher when moderate-to severe AEs were present (n=13 patients with moderate-to-severe AEs). Serum levels of macrophage inflammatory protein-1beta showed a significant continuous decrease from the baseline level (Friedman's test: chi (2)=23.9, df=4, P<0.001) only in non-responders. CONCLUSION: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1beta as potential blood biomarkers could be utilized to identify the responsiveness of patients to serotonin and norepinephrine reuptake inhibitor like milnacipran, or to identify those patients who may experience AEs strong enough to warrant discontinuation of treatment. PMID- 26677331 TI - Coping strategies and quality of life in schizophrenia: cross-sectional study. AB - BACKGROUND: The modern psychiatric view of schizophrenia spectrum disorders and their treatment has led to an increasing focus on coping strategies and the quality of life of these patients. In the present study, the authors examined the relationship between demographic data, the severity of symptoms, coping strategies, and the quality of life in psychotic patients. It is important to study the inner experience and striving of these individuals as it has been linked to their well-being and treatment adherence. METHODS: Psychiatric outpatients who met International Classification of Diseases, Tenth Revision criteria for a psychotic disorder (schizophrenia, schizoaffective disorder, or delusional disorder) were recruited in the study. Questionnaires measuring the coping strategies (The Stress Coping Style Questionnaire [SVF-78]), the quality of life (Quality of Life Satisfaction and Enjoyment Questionnaire [Q-LES-Q]), and symptom severity (objective and subjective Clinical Global Impression - objCGI; subjCGI) were assessed. The data were analyzed using one-way analysis of variance, Mann-Whitney U test, Pearson and Spearman correlation coefficients, and multiple regression analysis. RESULTS: A total of 109 psychotic patients were included in the study. The quality of life was significantly related to both the positive and negative coping strategies. The severity of disorder was highly negatively correlated with the quality of life score. The results of multiple stepwise regression analysis using the quality of life as a dependent variable showed that symptom severity (subjCGI, difference between subjCGI, and objCGI), negative coping strategies, positive coping strategies, and the difference between positive and negative coping strategies explain more than half variance. CONCLUSION: Our study suggests the importance of utilizing the positive coping strategies in improving the quality of life in patients with psychotic disorders. PMID- 26677332 TI - Early myocardial damage assessment in dystrophinopathies using (99)Tc(m)-MIBI gated myocardial perfusion imaging. AB - BACKGROUND: Early detection of muscular dystrophy (MD)-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m methoxyisobutylisonitrile ((99)Tc(m)-MIBI) gated myocardial perfusion imaging (G MPI) for MD. METHODS AND RESULTS: Ninety-one patients underwent (99)Tc(m)-MIBI G MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD) (n=77) or Becker muscular dystrophy (BMD; n=14). (99)Tc(m)-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using (99)Tc(m) MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (r s=0.534 [P<0.05] and r s=0.784 [P<0.05], respectively). Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05), but not in BMD patients. CONCLUSION: (99)Tc(m)-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD, and can serve as a candidate method for the evaluation of progression, prognosis, and assessment of the effect of glucocorticoid treatment in these patients. PMID- 26677333 TI - Docetaxel-related interstitial pneumonitis. AB - Docetaxel (Taxotere((r))) is an agent that is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer. In recent years, docetaxel-related interstitial lung disease (ILD) has been reported in several case series studies. The onset of ILD occurred ~10-20 days (median time: 18 days) after docetaxel administration. Here, we reported the case of a patient who had pulmonary toxicity of ILD within 3 days after using a relatively low-dose docetaxel administration. Although some articles have described patients who progressed to respiratory failure and needed intubation, this patient responded well to steroid treatment and discontinued docetaxel administration. PMID- 26677334 TI - Lung ultrasound for the diagnosis of childhood pneumonia: a safe and accurate imaging mode. AB - Pneumonia is the most common infectious cause of mortality in children worldwide. Chest x-ray (CXR) has been used as a supplementary mode in the diagnosis of pneumonia in children, but its frequent use might expose children to unnecessary ionizing radiation. In this review, we present up-to-date data of an alternative mode of imaging other than CXR in the diagnosis of pneumonia in children. We found that lung ultrasound is a safe and accurate mode of imaging that can be used by a health care provider in the cases of suspected pneumonia. It is more sensitive than CXR in the diagnosis of pneumonia and obviates the need for irradiation. PMID- 26677335 TI - Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1. AB - Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. PMID- 26677336 TI - Profile of nintedanib in the treatment of solid tumors: the evidence to date. AB - Angiogenesis is an essential process for tumor growth and metastasis, and remains a promising therapeutic target process in cancer treatment for several cancer types. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor (VEGF), was the first antiangiogenic agent approved for cancer therapy. Novel antiangiogenic agents, such as sunitinib, sorafenib, pazopanib, or vandetanib that target additional proangiogenic signaling pathways beyond VEGF, have also been approved for the treatment of various malignant diseases. While most of these agents are approved in combination with cytotoxic chemotherapy for indications including metastatic colorectal cancer, non-small-cell lung cancer, breast cancer, renal cell carcinoma (RCC), and gastric cancer, some are used as approved monotherapy for advanced RCC, hepatocellular carcinoma and medullary thyroid cancer. Major challenges to the success of antiangiogenic therapy include associated toxicity risks, limitation of efficacy through the possible development of resistance and induction or promotion of metastatic progression. Nintedanib (formally known as BIBF 1120) is a triple angiokinase inhibitor of VEGF, fibroblast growth factor, platelet-derived growth factor signaling with lesser activity against RET, Flt-3, and Src. Through this unique targeting profile nintedanib has demonstrated significant antitumor activity in several tumor types in preclinical studies. Nintedanib has also shown promising clinical efficacy in combination with docetaxel and has been approved for treating patients with locally advanced and metastatic non-small-cell lung cancer in Europe. Nintedanib has also been found to be clinically promising in terms of efficacy and safety in several other solid tumors including ovarian cancer (Phase III), RCC (Phase II), and prostate cancer (Phase II). This review article provides a comprehensive summary of the preclinical and clinical efficacy of nintedanib in the treatment of solid tumors. PMID- 26677337 TI - Correlations between plasma endothelin-1 levels and breakthrough pain in patients with cancer. AB - Endothelin-1 (ET-1) may be involved in driving pain in patients with advanced cancer. However, a few studies focus on the role of ET-1 in breakthrough pain (BP). The aim of this pivotal study was to explore the correlation between the plasma (ET-1) level and BP intensity. A total of 40 patients were enrolled in the study, and they were divided into two groups: BP group and non-BP group. Moreover, 20 healthy adults were used as the normal control group. Pain intensity was measured using visual analog scale (VAS) scores of 1-10. Plasma ET-1 levels were detected by an ET radioimmunoassay kit. Subsequently, the correlation of ET 1 level with the VAS score and cancer types was analyzed by Pearson's correlation coefficient. The plasma ET-1 level in the BP group (35.31+/-8.02 pg/mL) was higher than that in the non-BP group (29.51+/-6.78 pg/mL) and the normal control group (24.77+/-10.10 pg/mL, P<0.05). In addition, the VAS score in the BP group (7.45+/-0.82) was higher than that in the non-BP group (2.80+/-1.23, P<0.05). The plasma ET-1 level was positively correlated with the VAS score of the BP group (Pearson's r=0.42). There was no significant correlation between the plasma ET-1 level and VAS score of the non-BP group (Pearson's r=-0.22) or/and cancer types (P>0.05). The elevated plasma ET-1 levels were positively related to BP, and targeting ET-1 may provide a novel pain-reducing therapeutic treatment in BP. PMID- 26677338 TI - Non-leukemic myeloid sarcoma involving the vulva, vagina, and cervix: a case report and literature review. AB - Myeloid sarcoma (MS) is defined as a tumor mass consisting of myeloid blast with or without maturation occurring at an anatomical site other than bone marrow with normal architectural effacement. It can also precede the onset of leukemia which is called non-leukemic MS. Non-leukemic MS is a kind of rare disease and easy to be misdiagnosed as other common malignancies due to the rarity and nonspecific manifestation. We herein report an unusual case of non-leukemic MS involving the vulva, vagina, and cervix in a female patient. The bone marrow aspiration and biopsy of the patient revealed no hematological abnormality. Immunohistochemical staining of the biopsies was strongly positive for myeloperoxidase, CD68, leukocyte common antigen (LCA), CD117, CD34, CD38, CD79a, and negative for cytokeratin (CK), epithelial memberane antigen (EMA), CD2, CD3, CD20, CD5, CD138. Then a diagnosis of non-leukemic MS was made. Unfortunately, our patient received only one cycle of chemotherapy consisting of cytosine arabinoside and daunorubicin, then refused any further treatment and died 4 months after diagnosis. Although systemic chemotherapy is widely accepted to be a promising strategy, its benefit still needs to be further assessed. Certain questions still need to be answered for this disease: 1) Why can approximately 20% of the patients with non-leukemic MS remain disease-free after local therapy alone? 2) How many cycles of chemotherapy are needed for these patients after achievement of complete remission? 3) What are the prognostic or risk factors in these patients who have no abnormality of karyotype, fusion genes, or gene mutation to predict responsiveness to chemotherapy and outcome? 4) What is the risk factor for relapse? The rarity of non-leukemic MS makes it almost impossible to conduct large-scale randomized trials, but judicious study for each patient with MS is helpful for a further understanding of the nature of the disease. PMID- 26677340 TI - Gastrointestinal motility during sleep assessed by tracking of telemetric capsules combined with polysomnography - a pilot study. AB - Studies of gastrointestinal function during sleep are hampered by lack of applicable techniques. Recent development of a novel ambulatory telemetric capsule system, which can be used in conjunction with polysomnography, offers a solution to this problem. The 3D-Transit system consists of ingestible electromagnetic capsules traceable through a portable extracorporeal receiver while traversing the gut. During sleep monitored by polysomnography, gastrointestinal motility was concurrently investigated using 3D-Transit in nine healthy subjects. Overall, the amplitude of gastric contractions decreased with depth of sleep (light sleep, N2 versus deep sleep, N3; P<0.05). Progression through the small intestine did not change with depth of sleep (Kruskal-Wallis probability =0.1), and there was no association between nocturnal awakenings or arousals and the occurrence of colonic or small intestinal propagating movements. Basal colonic activity was suppressed during both deep sleep (P<0.05) and light sleep (P<0.05) when compared with nocturnal wake periods. In conclusion, the novel ambulatory 3D-Transit system combined with polysomnography allows minimally invasive and completely ambulatory investigation of associations between sleep patterns and gastrointestinal motility. PMID- 26677339 TI - Identification of potential drug targets by subtractive genome analysis of Escherichia coli O157:H7: an in silico approach. AB - Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen's survival but absent in its human host. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins. Further bio-informatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120. Ultimately, 44 non homologous essential proteins of E. coli O157:H7 were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets and DNA polymerase III alpha (dnaE) was the top-ranked among these targets. Moreover, druggability of each of the identified drug targets was evaluated by the DrugBank database. In addition, 3D structure of the dnaE was modeled and explored further for in silico docking with ligands having potential druggability. Finally, we confirmed that the compounds N-coeleneterazine and N-(1,4-dihydro-5H-tetrazol-5 ylidene)-9-oxo-9H-xanthene-2-sulfon-amide were the most suitable ligands of dnaE and hence proposed as the potential inhibitors of this target protein. The results of this study could facilitate the discovery and release of new and effective drugs against E. coli O157:H7 and other deadly human bacterial pathogens. PMID- 26677341 TI - Effect of zinc supplementation on body mass index and serum levels of zinc and leptin in pediatric hemodialysis patients. AB - INTRODUCTION: Zinc is an essential trace element for human nutrition, and its deficiency is associated with anorexia, poor food efficiency, growth retardation, and impaired neurological and immune systems. The zinc-deficiency rate is particularly high in many disease states, such as with end-stage renal disease patients undertaking hemodialysis. The aim of this study was to determine the effect of zinc supplementation on body mass index (BMI) and serum levels of zinc and leptin in pediatric hemodialysis patients. PATIENTS AND METHODS: This was a prospective clinical trial study in which 60 hemodialysis patients were randomly divided into two groups: group I received 50-100 mg zinc sulfate (equivalent to 11-22 mg elemental zinc) according to age, sex, and nutritional status of the child; and group II received placebo (cornstarch) twice daily for 90 days. Anthropometric measurements were taken, and serum zinc and leptin levels were determined by colorimetric test with 5-Br-3'-phosphoadenosine-5'-phosphosulfate and enzyme-linked immunosorbent assay, respectively, at days 0 and 90 of the study. RESULTS: Zinc supplementation resulted in a significant increase in mean serum zinc level and BMI. Serum leptin decreased significantly after supplementation in children under hemodialysis. A significant negative correlation was observed between serum zinc and leptin levels as a result of zinc supplementation. CONCLUSION: There was an increase in serum zinc level and BMI and decreased serum leptin after zinc supplementation in children under hemodialysis. PMID- 26677342 TI - Evolution of transversus abdominis plane infiltration techniques for postsurgical analgesia following abdominal surgeries. AB - Transversus abdominis plane (TAP) infiltration is a regional anesthesia technique that has been demonstrated to be effective for management of postsurgical pain after abdominal surgery. There are several different clinical variations in the approaches used for achieving analgesia via TAP infiltration, and methods for identification of the TAP have evolved considerably since the landmark-guided technique was first described in 2001. There are many factors that impact the analgesic outcomes following TAP infiltration, and the various nuances of this technique have led to debate regarding procedural classification of TAP infiltration. Based on our current understanding of fascial and neuronal anatomy of the anterior abdominal wall, as well as available evidence from studies assessing local anesthetic spread and cutaneous sensory block following TAP infiltration, it is clear that TAP infiltration techniques are appropriately classified as field blocks. While the objective of peripheral nerve block and TAP infiltration are similar in that both approaches block sensory response in order to achieve analgesia, the technical components of the two procedures are different. Unlike peripheral nerve block, which involves identification or stimulation of a specific nerve or nerve plexus, followed by administration of a local anesthetic in close proximity, TAP infiltration involves administration and spread of local anesthetic within an anatomical plane of the surgical site. PMID- 26677343 TI - Correlation of clinicopathological outcomes with changes in IHC4 status after NACT in locally advanced breast cancers: do pre-NACT ER/PR status act as better prognosticators? AB - BACKGROUND: Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management. PATIENTS AND METHODS: Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated. RESULTS: pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive. CONCLUSION: Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors. PMID- 26677344 TI - Comparison of obstetric anal sphincter injuries in nulliparous women before and after introduction of the EPISCISSORS-60((r)) at two hospitals in the United Kingdom. AB - AIM: To assess whether the introduction of episiotomy scissors specially designed to achieve a cutting angle of 60 degrees , EPISCISSORS-60((r)), in two hospitals in the UK would result in a reduction in obstetric anal sphincter injuries (OASIS) in nulliparous women. METHODS: A structured training program for all doctors and midwives provided a theoretical framework around OASIS including risk factors and the role of episiotomies and a practical hands-on training element to use EPISCISSORS-60((r)) correctly and to measure perineal body length and post suturing angles. Data for perineal body length, post-suturing angles, user feedback, episiotomy use, and incidence of OASIS were collected through specifically designed forms and the general hospital data collection system. RESULTS: Data were available for 838 nulliparous vaginal deliveries. Mean perineal body length was 37 mm in spontaneous vaginal delivery group (standard deviation [SD] =8.3, 95% confidence interval [CI] =34-39) and 38 mm in the operative vaginal delivery group (SD=8, 95% CI=35-40). Post-suturing episiotomy angles were 53 degrees (SD=6.5, 95% CI=50.7-55.8) in spontaneous vaginal deliveries and 52 degrees (SD=9.6, 95% CI=49-54) in operative vaginal deliveries. EPISCISSORS-60((r)) were rated as "good" to "very good" by 84% of users. There was a 47% increase in the number of episiotomies in nulliparous spontaneous vaginal deliveries at Poole (P=0.007) and a 16.5% increase in the number of episiotomies in nulliparous operative vaginal deliveries in Hinchingbrooke (P=0.003). There was an overall 11% increase in episiotomy numbers in nulliparous vaginal deliveries (P=0.08). There was a statistically significant OASIS reduction of 84% in nulliparous spontaneous vaginal deliveries in women who received an episiotomy (P=0.003). CONCLUSION: Initial results after introduction of EPISCISSORS-60((r)) show that the majority of health care professionals achieve post-suturing episiotomy angles between 40 degrees and 60 degrees . The results also show a significant increase in the use of episiotomies in the delivery of nulliparous women. There has been a statistically significant reduction in OASIS in nulliparous spontaneous vaginal deliveries. PMID- 26677345 TI - Health-profession students' teaching and learning expectations in Ugandan medical schools: pre- and postcommunity placement comparison. AB - PURPOSE: The benefits of community-based medical education for both students and teachers are becoming increasingly clear. However, there is paucity of information about the importance of incorporating students' thoughts in the community-based education curriculum and the impact it has on their intentions to work in rural communities. The purpose of this study was to assess the teaching and learning expectations before and after placement of health-profession students going for community placement for the first time and make suggestions for improvement of the community-based programs. METHODS: The study was a cross sectional survey with both structured and unstructured questions. Participants were recruited from four medical schools in Uganda targeting 100% participation of health-profession students going for community placement in 2014. In total, 454 and 305 participants responded to self-administered questionnaires before and after community placement, respectively; and they were from different programs and years of study. RESULTS: Students' learning expectations before placement, in ranking were: community engagement, interpersonal skills, community diagnosis, clinical skills, lifestyle practices, and patient management. After placement, the order of ranking was: interpersonal skills, community engagement, community diagnosis, lifestyle practices, clinical skills, and patient management. Most of the students had prior rural exposure and expected to do community engagement. However, after community placement they indicated having developed interpersonal skills. The various health-profession students were able to harmoniously work together to achieve a common purpose, which they find difficult to do in a classroom environment. CONCLUSION: Having student teams comprised of different health programs and years of study going for community placement together promoted peer-to-peer mentorship and enhanced team building during community placement. PMID- 26677346 TI - [AN EVALUATION OF JUSTICE AND RIGHT TO HEALTH CONCEPTS IN THE PERSPECTIVES OF ETHICAL THEORIES]. AB - Right to health is considered as a fundamental human right. However the realization of right to health is facing obstacles due to the scarce resources which are needed for the provision of health services. Besides the vast technological improvements in medical area leads to the development of diagnosis and treatment possibilities each and every day. Thus, the provision of health services becomes a subject of distributive justice. To define the concept of justice, first one should identify the conditions of demanding right to have something and then determine how and who is obliged to give the deserved. Ethical theories form their own paradigms of acting right regarding their anchor points and priority values. The basic concepts such as justice or right to health are considered and conceptualized within the paradigms of the ethical theories. Thus some ethical theories consider right to health as a natural constituent of human being, while some may consider it contextual and others may reject it completely. In a similar vein, justice and related concepts of justice such as formal and material principles of justice differ regarding the paradigm of the ethical theory in which we position ourselves. The paradigms of ethical theories demand different approaches from each other both in defining the concepts and implementations in practical life. This paper sets forth how justice and right to health is conceptualized in the virtue ethics, deontological ethics, liberal ethical theory and communitarian ethical theories. To this end first the general frame of each ethical theory and how justice is conceptualized within this frame is defined. Following that a discussion of the possibility of justification of the right to health within the context of ethical theory is perused. PMID- 26677347 TI - The Big Impact of Small Groups on College Drinking. AB - College drinking is a problem with severe academic, health, and safety consequences. The underlying social processes that lead to increased drinking activity are not well understood. Social Norms Theory is an approach to analysis and intervention based on the notion that students' misperceptions about the drinking culture on campus lead to increases in alcohol use. In this paper we develop an agent-based simulation model, implemented in MATLAB, to examine college drinking. Students' drinking behaviors are governed by their identity (and how others perceive it) as well as peer influences, as they interact in small groups over the course of a drinking event. Our simulation results provide some insight into the potential effectiveness of interventions such as social norms marketing campaigns. PMID- 26677348 TI - Reduced IL-33 plasma levels in aplastic anemia. AB - BACKGROUND: In this study, we aim to evaluate the balance of interleukin (IL)-33 and its soluble receptor sST2 in patients with aplastic anemia (AA). METHODS: Plasma IL-33, IL-17 and sST2 levels were measured in patients with active AA (n = 31), AA in remission (n = 29) and in healthy subjects (n = 30), using enzyme linked immunosorbent assays (ELISAs). RESULTS: The results showed that sST2 and IL-17 levels were significantly elevated in patients with active AA when compared to control subjects, but IL-33 levels were significantly lower in AA patients, which resulted in elevated sST2/IL-33 ratios in patients with active disease. During remission stages, the levels of these cytokines were comparable to those of healthy controls. CONCLUSIONS: The elevated levels of sST2/IL-33 in the plasma during active stages of the disease suggest a possible role in the pathogenesis and course of AA. PMID- 26677349 TI - Original approach for thrombolytic therapy in patients with Ilio-femoral deep vein thrombosis : 2 years follow-up. AB - OBJECTIVE: The aim of the study was to discuss the results of catheter-directed thrombolysis and complementary procedures to treat acute iliofemoral deep vein thrombosis (DVT) evaluating the safety and effectivness of an easy access such as the Great Saphenous Vein. METHODS AND MATERIALS: A total of 22 consecutive patients with iliofemoral thrombosis and two patients with femoro-popliteal thrombosis on recent onset diagnosed with Ultrasound Doppler and contrast venography underwent intrathrombus drip infusion of urokinase while intravenous heparin was continued using saphenical access. Residual venous stenosis were treated in six patients by percutaneous balloon Angioplasty and stenting. All patients underwent routine venous duplex imaging at 30 days, 3 months, 6 months and every 6 months thereafter. RESULTS: Complete patency of thrombosed veins was restored in 22 patients (91 %) with prompt symptomatic relief. There were no major complications in the immediate outcomes. At follow-up, two patients reported a persistant slim iliac vein stenosis, two patients had post-thrombotic syndrome, and two patients showed Deep Vein Reflux. CONCLUSION: Local thrombolysis using saphenical access was a safe and effective approach for the treatment of acute iliofemoral deep vein thrombosis. It seems to be a valid, easy and safe alternative, reducing the risks of haematoma and venous lesions, which can be observed when using femoral, popliteal, and trans-jugular access. PMID- 26677350 TI - The effects of whey protein with or without carbohydrates on resistance training adaptations. AB - BACKGROUND: Nutrition intake in the context of a resistance training (RT) bout may affect body composition and muscle strength. However, the individual and combined effects of whey protein and carbohydrates on long-term resistance training adaptations are poorly understood. METHODS: A four-week preparatory RT period was conducted in previously untrained males to standardize the training background of the subjects. Thereafter, the subjects were randomized into three groups: 30 g of whey proteins (n = 22), isocaloric carbohydrates (maltodextrin, n = 21), or protein + carbohydrates (n = 25). Within these groups, the subjects were further randomized into two whole-body 12-week RT regimens aiming either for muscle hypertrophy and maximal strength or muscle strength, hypertrophy and power. The post-exercise drink was always ingested immediately after the exercise bout, 2-3 times per week depending on the training period. Body composition (by DXA), quadriceps femoris muscle cross-sectional area (by panoramic ultrasound), maximal strength (by dynamic and isometric leg press) and serum lipids as basic markers of cardiovascular health, were analysed before and after the intervention. RESULTS: Twelve-week RT led to increased fat-free mass, muscle size and strength independent of post-exercise nutrient intake (P < 0.05). However, the whey protein group reduced more total and abdominal area fat when compared to the carbohydrate group independent of the type of RT (P < 0.05). Thus, a larger relative increase (per kg bodyweight) in fat-free mass was observed in the protein vs. carbohydrate group (P < 0.05) without significant differences to the combined group. No systematic effects of the interventions were found for serum lipids. The RT type did not have an effect on the adaptations in response to different supplementation paradigms. CONCLUSIONS: Post-exercise supplementation with whey proteins when compared to carbohydrates or combination of proteins and carbohydrates did not have a major effect on muscle size or strength when ingested two to three times a week. However, whey proteins may increase abdominal fat loss and relative fat-free mass adaptations in response to resistance training when compared to fast-acting carbohydrates. PMID- 26677351 TI - Evaluation of congruence among dietary supplement use and motivation for supplementation in young, Canadian athletes. AB - BACKGROUND: Dietary supplement use is endemic in young athletes; however, it is unclear if their choices are congruent with their motivation for supplementation and the established benefits of the dietary supplements. The aim of this study was to evaluate the relationships between dietary supplement use and self reported rationale in young athletes. METHODS: Canadian athletes (n = 567; 11-25 years; 76% club or provincial level, 24% national or higher) completed a questionnaire designed to assess supplementation patterns and motivation for supplementation. Chi square tests examined associations between dietary supplements and self-reported rationale for use. RESULTS: Vitamin and mineral supplements, including vitamin-enriched water, were associated with several health- and performance- related reasons (p < 0.001). Branched chain amino acids (BCAA) and glutamine were linked to improving diet and immune function (p < 0.01), but were more strongly associated with performance reasons, as were performance foods (protein powder, sport bars, sport gels, etc.). Plant extracts and fatty acids were primarily associated with health reasons, particularly immune support (p < 0.001). CONCLUSIONS: Congruencies exist between performance rationales and supplementation for common ergogenic aids, however, less so for vitamin and mineral supplements, vitamin-enriched water, and plant extracts. Incongruences were found between fatty acids, protein supplements, vitamin and mineral supplements, vitamin-enriched water, and plant extracts and health motivators for supplementation. Educational interventions are essential to ensure young athletes are using dietary supplements safely and effectively. PMID- 26677352 TI - Factors associated with experimentation of electronic cigarettes among Parisian teenagers in 2013. AB - BACKGROUND: Electronic cigarettes (e-cig.) became widely used among adults. Data are insufficient about e-cig. experimentation among youth. METHODS: To assess prevalence of e-cig. experimentation and associated factors among the 12 to 19 years old we analyse a cross sectional school based survey in the city of Paris, France in 2013 on a randomly selected sample of 2 % of schoolchildren (n = 3 279). Self-report questionnaire include demographic, individual and family smoking characteristics and questions about e-cig: "Have you ever used an e cigarette?"- "Did you use e-cigarette in the last 30 days?"-"Did you try e cigarette as a first tobacco product?". RESULTS: In 2013, 17.9 % (564) schoolchildren reported having experienced the e-cig (boys: 19.0 %, girls: 16.8 %) compared to 9.8 % in 2012. Experimentation rate increases from 5 % among the 12 to 30 % among the 16-year-old. E-cig. experimentation was significantly associated with 11 parameters including : age >15 years (OR: 0.66 (IC95 % = 0.46 0.94)); smoking 10 cigarettes or more (OR = 5.67 (IC95 % = 3.11-10.34)), best friends and siblings smoker (OR = 1.54 (IC95 % = 1.11-2.14)) and (OR = 1.88 (IC95 % = 1.41-2.52)); experimentation of shisha (OR = 2.60 (IC95 % = 1.75-3.86)), cannabis use (OR = 1.90 (IC95 % = 1.32-2.72)); having two parents who forbid smoking (OR = 2.32 (IC95 % = 1.63-3.30)). Only 5.6 % of the study population (and 32.5 % of e-cig. experimenters (183/564)) have used it in the last 30 days; 1.7 % of the study population and 10.0 % of e-cig. experimenters were non-smokers (56/564). CONCLUSIONS: Rate of e-cig. experimentation among schoolchildren increased by 8.1 % in 1 year. Non-smoking youth may use e-cig. Prospective studies are urgently needed to assess the evolution of e-cig. use both among smoking and non-smoking youth. PMID- 26677353 TI - Bioresorbable vascular scaffold implantation in acute coronary syndromes: clinical evidence, tips and tricks. AB - Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is routine treatment for patients with acute coronary syndromes (ACS). However, permanent metallic caging of the vessel has several shortcomings, such as side branch jailing and impossibility of late lumen enlargement. Moreover, DES PCI is affected by vasomotion impairment. In ACS a high thrombus burden and vasospasm lead to a higher risk of acute and late acquired stent malapposition than in stable patients. This increases the risk of acute, late and very late stent thrombosis. In this challenging clinical setting, the implantation of bioresorbable vascular scaffolds (BVS) could represent an appealing therapeutic option. Temporary vessel scaffolding has proved to have several advantages over metallic stent delivery, such as framework reabsorption, late lumen enlargement, side branch patency, and recovery of physiological reactivity to vasoactive stimuli. In the thrombotic environment of ACS, BVS implantation has the benefit of capping the thrombus and the vulnerable plaque. Bioresorbable vascular scaffolds also seems to reduce the incidence of angina during follow-up. Acute coronary syndromes patients may therefore benefit more from temporary polymeric caging than from permanent stent platform implantation. The aim of this review is to update the available knowledge concerning the use of BVS in ACS patients, by analyzing the potential pitfalls in this challenging clinical setting and presenting tricks to overcome these limitations. PMID- 26677354 TI - Bleeding risk stratification in acute coronary syndromes. Is it still valid in the era of the radial approach? PMID- 26677355 TI - Vitamin D: evidence for an association with coronary collateral circulation development? PMID- 26677356 TI - Percutaneous interventions in cardiology in Poland in the year 2014. Summary report of the Association of Cardiovascular Interventions of the Polish Cardiac Society AISN PTK. AB - INTRODUCTION: The Board of the Association of Cardiovascular Interventions of the Polish Cardiac Society (AISN PTK) publishes annual data from the National PCI Registry (ORPKI) operated by the Jagiellonian University Medical College in Krakow. AIM: For the first time the AISN PTK report is based on the new electronic database implemented in Poland on January 1(st), 2014. MATERIAL AND METHODS: In 2014, there were 155 invasive cardiology centers registered in the ORPKI database (an increase by 1 center in comparison to 2013) and 92% of them had 24/7 percutaneous (PCI) duty. For the first time the number of catheterization laboratories (cath labs) in Poland remained stable, and even though there was an increase by 1 in absolute numbers, 2 cath labs ceased to admit patients in 2014. This means that the number of active cath labs per 1 million inhabitants is similar to last year and equals 4. RESULTS: In comparison to 2013, there was a significant increase in the total number of coronary angiographies. There were 226 713 angiographies in 2014. The total number of PCI procedures was 126 241, which is 5.1% more than in 2013. CONCLUSIONS: There was a significant increase in the overall number of coronary angiographies and PCIs in Poland in 2014. The use of attributes of modern interventional cardiology such as drug-eluting stents and bioabsorbable vascular stents is growing as well as more frequent choice of a radial access site by PCI operators even in ST-elevation myocardial infarction patients. One should also note a significant rise in the use of additional imaging or diagnostic tools such as fractional flow reserve, intravascular ultrasound and optical coherent tomography. PMID- 26677357 TI - Accuracy of bleeding scores for patients presenting with myocardial infarction: a meta-analysis of 9 studies and 13 759 patients. AB - INTRODUCTION: Due to its negative impact on prognosis, a clear assessment of bleeding risk for patients presenting with acute coronary syndrome (ACS) remains crucial. Different risk scores have been proposed and compared, although with inconsistent results. AIM: We performed a meta-analysis to evaluate the accuracy of different bleeding risk scores for ACS patients. MATERIAL AND METHODS: All studies externally validating risk scores for bleeding for patients presenting with ACS were included in the present review. Accuracy of risk scores for external validation cohorts to predict major bleeding in patients with ACS was the primary end point. Sensitivity analysis was performed according to clinical presentation (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)). RESULTS: Nine studies and 13 759 patients were included. CRUSADE, ACUITY, ACTION and GRACE were the scores externally validated. The rate of in-hospital major bleeding was 7.80% (5.5-9.2), 2.05% (1.5-3.0) being related to access and 2.70% (1.7-4.0) needing transfusions. When evaluating all ACS patients, ACTION, CRUSADE and ACUITY performed similarly (AUC 0.75: 0.72-0.79; 0.71: 0.64-0.80 and 0.71: 0.63-0.77 respectively) when compared to GRACE (0.66; 0.64-0.67, all confidence intervals 95%). When appraising only STEMI patients, all the scores performed similarly, while CRUSADE was the only one externally validated for NSTEMI. For ACTION and ACUITY, accuracy increased for radial access patients, while no differences were found for CRUSADE. CONCLUSIONS: ACTION, CRUSADE and ACUITY perform similarly to predict risk of bleeding in ACS patients. The CRUSADE score is the only one externally validated for NSTEMI, while accuracy of the scores increased with radial access. PMID- 26677358 TI - 25-Hydroxy-vitamin D level may predict presence of coronary collaterals in patients with chronic coronary total occlusion. AB - INTRODUCTION: Sufficient coronary collateral circulation (CCC) protects myocardial tissue against ischemia in patients with coronary chronic total occlusion (CTO). Vitamin D is a steroid hormone which has been related to increased prevalence of hypertension, left ventricular hypertrophy, heart failure, peripheral artery disease, coronary artery disease, myocardial infarction and cardiovascular mortality. AIM: To investigate whether there is an association between serum 25-hydroxy-vitamin D levels and development of CCC in patients with coronary CTO. MATERIAL AND METHODS: A total of 188 patients with CTO at coronary angiography were included in this study. Vitamin D and parathyroid hormone (PTH) levels were measured on the day of coronary angiography. Development of collateral circulation was graded according to the Rentrop classification after coronary angiography. Then, patients were divided into two groups on the basis of CCC grades: group 1 included 68 (36%) patients with poorly developed CCC, and group 2 included 120 (64%) patients with well developed CCC. RESULTS: Patients with poorly developed CCC had significantly lower serum 25-hydroxy-vitamin D levels compared to those with well-developed CCC (20 +/-3 vs. 30 +/-6 ng/ml, p<0.0001). Multivariate logistic regression analysis indicated serum 25-hydroxyvitamin D (25(OH)D) (OR = 1.794, 95% confidence interval (CI): 1.453-2.216; p<0.001) as an independent predictor of poor collateral flow in patients with CTO. CONCLUSIONS: Low vitamin D level is an independent predictor of poor CCC in patients with CTO. PMID- 26677359 TI - The usefulness of plateletcrit to predict cardiac syndrome X in patients with normal coronary angiogram. AB - INTRODUCTION: Cardiac syndrome X (CSX) is a clinical entity defined as the triad of typical angina pectoris on exercise, electrocardiographic or metabolic findings of ischemia and normal epicardial coronary arteries. Platelets, whose amount in the blood is indicated with plateletcrit (PCT), play an important role in inflammatory and thrombotic processes and the physiopathology of cardiovascular events. AIM: To investigate the association between cardiac syndrome X and PCT and platelet count. MATERIAL AND METHODS: A total of 113 patients with normal coronary angiogram were included in the study. Fifty patients with typical chest pain and evidence of myocardial ischemia in non invasive tests formed the CSX patient group. The control group consisted of 63 age- and gender-matched patients with normal coronary arteries but without angina. RESULTS: The mean PCT value of the CSX group was significantly higher than that of the control group (0.22 +/-0.06 vs. 0.19 +/-0.04; respectively, p=0.03). Higher PCT was found to be associated with the presence of CSX in patients with normal coronary arteries by multivariate logistic regression analysis. CONCLUSIONS: We suggest that high PCT may predict the presence of cardiac syndrome X in patients with normal coronary arteries. The value of PCT appears additive to conventional expensive methods commonly used in CSX prediction. PMID- 26677360 TI - The relationship between serum bilirubin concentration and coronary artery ectasia. AB - INTRODUCTION: The pathophysiology of coronary artery ectasia (CAE) has not been clearly identified, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis have been reported. Several studies have demonstrated that higher serum bilirubin inhibits the inflammation and proliferation of vascular smooth muscle cells; also there is a relationship between serum bilirubin and cardiovascular disease. However, the relationship between bilirubin and CAE is still unknown. AIM: We compared serum bilirubin concentration between CAE patients and controls. MATERIAL AND METHODS: This study included 50 CAE patients (20 male, mean age: 60.26 +/-10.6 years) and 30 control persons (10 male, mean age: 57.86 +/-11.6 years). These participants underwent concurrent routine biochemical tests and leukocyte count, hemoglobin, hematocrit and platelet count in whole blood. These parameters were compared between groups. RESULTS: No statistically significant difference was found between the two groups in terms of basic characteristics. Total, direct and indirect serum bilirubin levels were significantly lower among persons with CAE patients than controls (0.37 +/-0.4 vs. 0.71 +/-0.6 and 0.13 +/-0.1 vs. 0.27 +/-0.2 and 0.24 +/-0.2 vs. 0.43 +/-0.4 mg/dl; all p<0.001, respectively). CONCLUSIONS: Our study revealed a relationship between serum bilirubin and CAE. PMID- 26677361 TI - Evaluation of serum prolidase activity in patients with slow coronary flow. AB - INTRODUCTION: Slow coronary flow (SCF) is described as the slow passage of contrast to distal coronaries despite anatomically normal coronary arteries. It has been shown that increased serum prolidase activity (SPA) correlates with collagen turnover. Increased collagen turnover might be associated with the development of atherosclerotic plaques. AIM: To investigate the relationship between serum prolidase activity and slow coronary flow. MATERIAL AND METHODS: This cross-sectional study included 40 SCF patients (mean age: 55.0 +/-9.5 years, 20 females) and 40 controls (mean age: 53.9 +/-8.2 years, 21 females) with normal coronary anatomy and normal coronary flow. The Thrombolysis in Myocardial Infarction (TIMI) frame-count (TFC) method was used for SCF diagnosis. Serum prolidase activity was measured spectrophotometrically, and the relevant parameters were compared between the groups. RESULTS: There were no statistically significant differences between the SCF and control groups in terms of basic demographic, clinical, and laboratory data. However, the SPA was significantly higher in the SCF group compared to the control (702.7 +/-13.8 and 683.9 +/-13.2 respectively, p<0.001). Serum prolidase activity was significantly correlated with the mean TFC (r=0.463, p<0.001). The overall findings of this study support the predictive accuracy of the serum prolidase activity in our cohort, with a statistically significant ROC value of 681.3. CONCLUSIONS: Our study showed that SPA was increased in SCF patients. The activity of this enzyme was significantly correlated with the mean TFC. PMID- 26677362 TI - Impact of pre-hospital electrocardiogram teletransmission on time delays in ST segment elevation myocardial infarction patients: a single-centre experience. AB - INTRODUCTION: Delay in diagnosis and treatment has a great influence on morbidity and mortality of ST-segment elevation myocardial infarction (STEMI) patients. Every 30 min of delay in reperfusion is associated with an 8% increase in mortality. ECG teletransmission was proved to effectively shorten time delays in STEMI treatment. In 2012 an ECG teletransmission program was introduced in the Lower Silesia region. AIM: To assess the frequency of ECG teletransmission in STEMI patients and its influence on time delays. MATERIAL AND METHODS: We conducted a retrospective analysis of all patients admitted to our hospital with STEMI in 2013. Time delays, treatment and clinical characteristics of patients with and without teletransmission performed were compared. RESULTS: The study included 137 patients, of whom 49 (36%) had teletransmission performed. Direct transport to a percutaneous coronary intervention (PCI)-capable hospital was more frequent in patients with ECG teletransmission performed (88% vs. 63%, p = 0.002). In patients with teletransmission pain-emergency room time and total ischemic time were shorter (respectively 125 (91-184) min vs. 201 (113-339) min, p = 0.001 and 159 (136-244) min vs. 259 (170-389) min, p < 0.001). There were no differences in in-hospital delay, patients' characteristics, or applied therapy. CONCLUSIONS: The percentage of STEMI patients who had ECG teletransmission performed was low. Patients with ECG teletransmission had a shorter total ischemic time and lower percentage of indirect transport to a PCI-capable hospital. PMID- 26677363 TI - The utility of cardiac magnetic resonance imaging in Kounis syndrome. AB - INTRODUCTION: Current diagnostic measurements used to assess myocardial involvement in Kounis syndrome, such as electrocardiography (ECG), cardiac enzymes, and troponin levels, are relatively insensitive to small but potentially significant functional change. According to our review of the literature, there has been no study using magnetic resonance imaging (MRI) on Kounis syndrome except for one case report. AIM: To identify the findings of dynamic contrast enhanced magnetic resonance imaging (CE-MRI) in patients with Kounis syndrome (KS) type 1. MATERIAL AND METHODS: We studied 26 patients (35 +/-11.5 years, 53.8% male) with known or suspected KS type 1. The patients underwent precontrast, first-pass, and delayed enhancement cardiac MRI (DE-MRI). Contrast enhancement patterns, edema, hypokinesia, and localization for myocardial lesions were evaluated in all KS type 1 patients. RESULTS: Contrast-enhanced magnetic resonance imaging demonstrated an early-phase subendocardial contrast defect, and T2-weighted images showed high-signal intensity consistent with edema in lesion areas. None of the lesion areas was found upon contrast enhancement on DE-MRI. The area of early-phase subendocardial contrast defect was reported as follows: the interventricular septum in 14 (53.8%) patients, the left ventricular lateral wall in 8 (30.7%), and the left ventricular apex in 4 (15.4%). CONCLUSIONS: Dynamic cardiac MR imaging is a reliable tool for assessing cardiac involvement in Kounis syndrome. Delayed contrast-enhanced images show normal washout in the subendocardial lesion area in patients with Kounis syndrome type 1. PMID- 26677364 TI - Relationship of platelet indices with acute stent thrombosis in patients with acute coronary syndrome. AB - INTRODUCTION: Despite major advances in stent technology and antithrombotic therapy, the development of stent thrombosis continues to be a major problem in patients who have undergone percutaneous coronary intervention (PCI). Although a few studies have investigated the relationship between early stent thrombosis and platelet activity, the relationship between acute stent thrombosis (AST) (within the first 24 h) and platelet indices is unclear. AIM: We investigated the relationship between AST development and platelet indices in acute coronary syndrome patients. MATERIAL AND METHODS: In our case-control study, 33 patients who underwent PCI with subsequent AST development and 59 patients without AST were selected by propensity analysis. We compared the clinical, angiographic, and laboratory data between the AST and control groups. RESULTS: Mean platelet volume (MPV) (p=0.002) and platelet distribution width (p=0.014) were significantly higher and platelet count (p=0.017) was significantly lower in the AST group. Logistic regression analyses showed that MPV was a significant independent predictor of AST (OR = 1.67; 95% CI: 1.11-2.51; p=0.013). In the ROC analyses, the cut-off value of MPV to detect AST was > 9.1 fl with a sensitivity of 90.9%, a specificity of 42.4%, a positive predictive value of 46.9% and a negative predictive value of 89.3% (AUC: 0.687, 95% CI: 0.582-0.780, p=0.001). CONCLUSIONS: Our study shows that baseline MPV predicts the development of AST in patients with ACS. Mean platelet volume therefore might be an easily accessible marker in the identification of patients at high risk for the development of AST. PMID- 26677365 TI - A rare case of double infarction treated with primary percutaneous coronary intervention. PMID- 26677367 TI - De Winter sign in a patient with left main coronary artery occlusion. PMID- 26677366 TI - The use of modern interventional cardiology tools to verify lesion significance and optimize procedural outcome in a diabetic patient with multivessel disease. PMID- 26677368 TI - Snake-like hypermobile masses in three chambers of the heart: very unusual metastasis of squamous cell carcinoma. PMID- 26677369 TI - The importance of particular coronary collaterals' pathway in acute coronary syndrome. PMID- 26677370 TI - Hybrid atrial septal defect closure in a child with positional anomaly of the heart and thoracic wall abnormalities. PMID- 26677371 TI - Proximal end of 15-year-old ventricular electrode penetrating pulmonary tissue - a source of infection and a challenge for transvenous lead extraction. PMID- 26677372 TI - Aneurysm formation after paclitaxel-eluting balloon angioplasty used to treat coronary artery restenosis after plain old balloon angioplasty - case report and review of the literature. PMID- 26677373 TI - Acute two-vessel occlusion due to simultaneous very late stent thrombosis following sirolimus-eluting stent implantation: a case report and review of the literature. PMID- 26677374 TI - Undeployed and uncrushed coronary stent in the proximal region of the normal left anterior descending artery revealed four years after intervention. PMID- 26677376 TI - Coronary artery computed tomography as the first-choice imaging diagnostics in patients with high pre-test probability of coronary artery disease (CAT-CAD). AB - INTRODUCTION: The primary diagnostic examination performed in patients with a high pre-test probability of coronary artery disease (CAD) is invasive coronary angiography. Currently, approximately 50% of all invasive coronary angiographies do not end with percutaneous coronary intervention (PCI) because of the absence of significant coronary artery lesions. It is desirable to eliminate such situations. There is an alternative, non-invasive method useful for exclusion of significant CAD, which is coronary computed tomography angiography (CCTA). AIM: We hypothesize that use of CCTA as the first choice method in the diagnosis of patients with high pre-test probability of CAD may reduce the number of invasive coronary angiographies not followed by interventional treatment. Coronary computed tomography angiography also seems not to be connected with additional risks and costs of the diagnosis. Confirmation of these assumptions may impact cardiology guidelines. MATERIAL AND METHODS: One hundred and twenty patients with indications for invasive coronary angiography determined by current ESC guidelines regarding stable CAD are randomized 1 : 1 to classic invasive coronary angiography group and the CCTA group. RESULTS: All patients included in the study are monitored for the occurrence of possible end points during the diagnostic and therapeutic cycle (from the first imaging examination to either complete revascularization or disqualification from the invasive treatment), or during the follow-up period. CONCLUSIONS: Based on the literature, it appears that the use of modern CT systems in patients with high pre-test probability of CAD, as well as appropriate clinical interpretation of the imaging study by invasive cardiologists, enables precise planning of invasive therapeutic procedures. Our randomized study will provide data to verify these assumptions. PMID- 26677377 TI - Prime time for veno-arterial extracorporeal membrane oxygenation in 24-7 interventional cardiology center? PMID- 26677378 TI - Platelet/lymphocyte ratio was associated with impaired myocardial perfusion and both in-hospital and long-term adverse outcome in patients with ST-segment elevation acute myocardial infarction undergoing primary coronary intervention. AB - INTRODUCTION: Platelet/lymphocyte ratio (PLR) has been shown to be an inflammatory and thrombotic biomarker for coronary heart disease, but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. AIM: To investigate the relationship between PLR and no reflow, along with the in-hospital and long-term outcomes in patients with STEMI. MATERIAL AND METHODS: In the present study, we included 304 consecutive patients suffering from STEMI who underwent primary percutaneous coronary intervention (p PCI). Patients were stratified according to PLR tertiles based on the blood samples obtained in the emergency room upon admission. No-reflow after p-PCI was defined as a coronary thrombolysis in myocardial infarction (TIMI) flow grade <= 2 after vessel recanalization, or TIMI flow grade 3 together with a final myocardial blush grade (MBG) < 2. RESULTS: The mean follow-up period was 24 months (range: 22-26 months). The number of patients characterized with no-reflow was counted to depict increments throughout successive PLR tertiles (14% vs. 20% vs. 45%, p < 0.001). In-hospital major adverse cardiovascular events and death increased as the PLR increased (p < 0.001, p < 0.001). Long-term MACE and death also increased as the PLR increased (p < 0.001, p < 0.001). Multivariable logistic regression analysis revealed that PLR remained an independent predictor for both in-hospital (OR = 1.01, 95% CI: 1.00-1.01; p = 0.002) and major long term (OR = 1.01, 95% CI: 1.00-1.01; p < 0.001) adverse cardiac events. CONCLUSIONS: Platelet/lymphocyte ratio on admission is a strong and independent predictor of both the no-reflow phenomenon and long-term prognosis following p PCI in patients with STEMI. PMID- 26677375 TI - Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls. AB - Antiplatelet therapy with P2Y12 receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome, after percutaneous coronary intervention and in secondary prevention of atherothrombotic events. Clopidogrel used to be the most broadly prescribed P2Y12 receptor inhibitor with undisputable benefits especially in combination with aspirin, but a considerable number of clopidogrel-treated patients experience adverse thrombotic events in whom insufficient P2Y12-inhibition and a consequential high on-treatment platelet reactivity is a common finding. This clinically relevant limitation of clopidogrel has driven the increased use of new antiplatelet agents. Prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo pyrimidine) feature more potent and predictable P2Y12-inhibition compared to clopidogrel, which translates into improved ischemic outcomes. However, excessive platelet inhibition and consequential low on-treatment platelet reactivity comes at the price of increased risk of major bleeding. The majority of randomized clinical trials failed to demonstrate improved clinical outcomes with platelet function testing and tailored antiplatelet therapy, but results of all recent trials of potent antiplatelets and prolonged antiplatelet durations point towards a need for individualized antiplatelet approach in order to decrease thrombotic events without increasing bleeding. This review focuses on potential strategies for personalizing antiplatelet treatment. PMID- 26677380 TI - Transfemoral aortic valve implantation in severe aortic stenosis patients with prior mitral valve prosthesis. AB - INTRODUCTION: Transcatheter aortic valve implantation for severe symptomatic aortic stenosis in patients with a previous mitral valve prosthesis is technically challenging, and pre-procedural comprehensive assessment of these patients before transcatheter aortic valve implantation is vital for an uncomplicated and successful procedure. AIM: We want to share our experience with transcatheter aortic valve implantation in patients with a preexisting functional mitral valve prosthesis and describe a series of important technical and pre procedural details. MATERIAL AND METHODS: At our center, 135 patients with symptomatic severe aortic stenosis were treated with transcatheter aortic valve implantation. Six of them with a preexisting mitral valve prosthesis received an Edwards SAPIEN XT valve through the transfemoral route. RESULTS: Transcatheter aortic valve implantation was performed successfully in all 6 patients without any deformation of the cobalt-chromium/steel stents of the aortic valve bioprosthesis. Also no distortion or malfunction in the mitral valve prosthesis was observed after the procedure. There were no complications during the hospitalization period. Post-procedural echocardiography revealed no or mild aortic paravalvular regurgitation and normal valve function in all the patients. In addition, serial echocardiographic examination demonstrated that both the stability and function of the aortic and mitral prosthetic valves were normal without any deterioration in the gradients and the degree of the regurgitation at long-term follow-ups. CONCLUSIONS: Our experience confirms that transcatheter aortic valve implantation is technically feasible in patients with previous mitral valve replacement but comprehensive evaluation of patients by multimodal imaging techniques such as transesophageal echocardiography and multislice computed tomography is mandatory for a successful and safe procedure. PMID- 26677379 TI - Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction. AB - INTRODUCTION: Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. AIM: In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. MATERIAL AND METHODS: We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, alpha-tocopherol, beta-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. RESULTS: Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. CONCLUSIONS: Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease. PMID- 26677381 TI - Low prevalence of collateral cerebral circulation in the circle of Willis in patients with severe carotid artery stenosis and recent ischemic stroke. AB - INTRODUCTION: The circle of Willis is thought to play a key role in development of collateral flow in patients with internal carotid artery stenosis (ICAS). AIM: To assess flow in the circle of Willis in patients with recent ischemic stroke (IS). MATERIAL AND METHODS: The study included 371 patients, 102 symptomatic with severe ICAS and recent IS (within the last 3 months) (group I) and 269 asymptomatic with severe ICAS (group II). Flow in the middle (MCA), anterior (ACA) and posterior (PCA) cerebral arteries and pattern of the cross-flow through anterior (ACoA) and posterior (PCoA) communicating arteries were assessed with transcranial color-coded Doppler ultrasonography (TCCD). RESULTS: The ACoA or PCoA was less prevalent in group I than in group II (54% vs. 78%, p < 0.001 and 20% vs. 42%, p < 0.001, respectively), resulting in lower peak-systolic velocity (PSV) in the MCA in group I vs. group II (p = 0.015). Any collateral pathway was present in 67% of patients in group I, compared to 86% in group II (p < 0.001). Both PSV and end-diastolic (EDV) flow velocity in the ACA were lower in patients with recent IS, compared to asymptomatic subjects (71 +/-24 cm/s vs. 86 +/-34 cm/s, p < 0.001 and 32 +/-12 cm/s vs. 37 +/-17 cm/s, p = 0.038, respectively). Presence of ACoA or PCoA and higher PSV in the MCA and ACA were associated with significant risk reduction of IS (RR = 0.28 (95% CI = 0.16-0.49, p < 0.001), RR = 0.28 (95% CI = 0.15-0.52, p < 0.001), RR = 0.97 (95% CI = 0.96-0.99, p < 0.001), RR = 0.99 (95% CI = 0.98-0.99, p < 0.032), respectively). However, ROC curves failed to show reliable MCA or ACA PSV cut-offs for IS risk assessment. CONCLUSIONS: The ACoA and PCoA seem to play a key role in the evaluation of IS risk in subjects with severe ICAS. PMID- 26677382 TI - Percutaneous closure of coronary artery fistula: long-term follow-up results. AB - INTRODUCTION: Coronary artery fistula consists of abnormal congenital connections between a coronary artery and cardiac chambers, a coronary vessel or an intrathoracic vessel that can be complicated by intracardiac shunts, endocarditis, myocardial infarction, or coronary aneurysms. Recent reports have emphasized the efficacy of percutaneous transcatheter techniques as an alternative to surgical closure, but the reported experience is relatively limited. AIM: To assess angiographic outcomes in a series of 20 patients who underwent transcatheter closure of coronary artery fistula. MATERIAL AND METHODS: We evaluated all patients presenting with significant coronary artery fistula and undergoing transcatheter closure with coils and a vascular plug between March 2008 and June 2012. RESULTS: There were 20 patients (14 men; mean age: 53 +/-8 years) with coronary artery fistula. Fistula diameter ranged from 4 to 12 mm; an average of three coils were used in the percutaneous procedure. Post-deployment angiograms demonstrated complete occlusion in all patients. The patients were followed up for 4 +/-1.6 years. The control coronary computed tomographic angiography was performed in the sixth month and no patients had recanalization of the embolized vessel. CONCLUSIONS: Percutaneous closure of coronary artery fistula is a safe and effective treatment modality. PMID- 26677383 TI - Bioresorbable vascular scaffolds in saphenous vein grafts (data from OCTOPUS registry). PMID- 26677384 TI - Rescue extracorporeal membrane oxygenation for refractory cardiogenic shock. PMID- 26677385 TI - Successful treatment of acutely occluded left main coronary artery in a patient with an aortic valve bioprosthesis. PMID- 26677386 TI - Patient with ST-elevation myocardial infarction, coronary artery embolism and no signs of coronary atherosclerosis in angiography. PMID- 26677387 TI - Coronary vasospasm-induced periodic ventricular fibrillation and successful ablation through coronary stenting. PMID- 26677388 TI - Optimal interventional treatment in a patient with occlusion of the brachiocephalic trunk and left subclavian artery with "double" steal syndrome. PMID- 26677389 TI - Successful percutaneous closure of a tortuous coronary artery to pulmonary artery fistula using the anchor technique: a different approach. PMID- 26677390 TI - Contralateral pneumothorax after cardiac pacemaker implantation. PMID- 26677391 TI - A novel treatment approach for common carotid artery bifurcation aneurysms. PMID- 26677392 TI - Fulminant heart failure due to giant cell myocarditis affecting the left ventricle. AB - A 56-year-old woman, previously healthy, was hospitalized after an episode of ventricular tachycardia in the course of infection. In view of the fulminant course of heart failure the patient was connected to an extracorporeal membrane oxygenation (ECMO) system. After 3 weeks of treatment with ECMO the patient received a heart transplant. A histopathological examination of the tissues of the explanted heart revealed giant cell myocarditis. The patient was treated with immunosuppression based on induction therapy followed by a standard regimen with steroids. Currently, the patient remains in good general condition with an left ventricular ejection fraction of 60%. PMID- 26677393 TI - Severe thrombocytopenia soon after drug-eluting stent implantation in ST elevation myocardial infarction. AB - Thrombocytopenia is among the most frequent haematological issues in patients hospitalised with myocardial infarction. We discuss the case of a 77-year-old male who was admitted to hospital on the 4(th) hour of ST-elevation myocardial infarction of the anterior wall. A percutaneous coronary intervention to critically stenoted initial segment of the anterior descending branch was performed. A few days later he started developing symptomatic thrombocytopenia. On the course of his long hospitalization we faced many important problems, concerning both diagnosis and treatment of these co-existing conditions. PMID- 26677394 TI - End stage renal disease patients have a skewed T cell receptor Vbeta repertoire. AB - BACKGROUND: End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vbeta repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vbeta repertoire was assessed. RESULTS: A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vbeta repertoire compared to age and cytomegalovirus (CMV) - IgG serostatus matched healthy individuals (31.4 %, P < 0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vbeta repertoire. More differentiated CD8(+) T cells were observed in young ESRD patients with a shifted TCR Vbeta repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vbeta skewing. CONCLUSIONS: ESRD significantly skewed the TCR Vbeta repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity. PMID- 26677395 TI - Occupational exposure to blood borne pathogens among healthcare workers: a cross sectional study of a registry in Colombia. AB - BACKGROUND: Occupational exposure to blood borne pathogens caused by percutaneous injuries or mucosal contamination is frequent among Healthcare Workers (HCW). METHODS: A cross-sectional analysis of HCW with an occupational exposure to blood reported to professional risk insurance agencies between 2009 and 2014 was performed. Comparisons between groups according to exposure level (mild, moderate, and severe) were evaluated. RESULTS: Two thousand, four hundred three reports were classified according exposure as mild 2.7 %, moderate 74.8 %, severe 21.9 %. Factors related: health sciences student with mild exposure events [adjusted odds ratio (AOR) 11.91, 95 % CI 5.13-27.61, p < 0.00001], and physician with moderate exposure events (AOR 1.90, 95 % CI 1.17-3.07, p = 0.009). Factors inversely related: physician with severe exposure events (AOR 0.54, 95 % CI 0.32 0.91, p = 0.02) and health sciences student with moderate exposure events (AOR 0.08, 95 % CI 0.04-0.15, p < 0.00001). It was found an important relationship between severe events with infectious diseases specialist assessment, and follow up adherence. Additionally, a case of Human Immunodeficiency Virus seroconversion was presented (0.0004 %), no other seroconversions were observed. CONCLUSIONS: Occupational exposure events must be managed according to established protocols, but adherence failure was evident with the exception of severe exposure cases. Thus, interventions to enhance occupational safety are required. Occupation must be considered as a risk factor during initial assessment of events. PMID- 26677397 TI - Hydroxyl radical-aided thermal pretreatment of algal biomass for enhanced biodegradability. AB - BACKGROUND: Algal biomass, known as a potential feedstock for biofuel production, has cell wall structures that differ from terrestrial biomass. The existing methods for processing algae are limited to conventional pretreatments for terrestrial biomass. RESULTS: In this study, we investigated a novel hydroxyl radical-aided approach for pretreating different types of algal biomass. In this process, hydroxyl radicals formed by a Fenton system were employed in combination with heating to alter the crystalline structure and hydrogen bonds of cellulose in the algal biomass. FeSO4 and H2O2 at low concentrations were employed to initiate the formation of hydroxyl radicals. This method releases trapped polysaccharides in algal cell walls and converts them into fermentable sugars. The effects of temperature, time, and hydroxyl radical concentration were analyzed. The optimal pretreatment condition [100 degrees C, 30 min, and 5.3 mM H2O2 (determined FeSO4 concentration of 11.9 mM)] was identified using a central composite design. Complete (100 %) carbohydrate recovery was achieved with some algal biomass without formation of inhibitors such as hydroxymethylfurfural and furfural as by-products. Both microalgal and macroalgal biomasses showed higher enzymatic digestibility of cellulose conversion (>80 %) after the milder pretreatment condition. CONCLUSION: Hydroxyl radical-aided thermal pretreatment was used as a novel method to convert the carbohydrates in the algal cell wall into simple sugars. Overall, this method increased the amount of glucose released from the algal biomass. Overall, enhanced algal biomass digestibility was demonstrated with the proposed pretreatment process. The new pretreatment requires low concentration of chemical solvents and milder temperature conditions, which can prevent the toxic and corrosive effects that typically result from conventional pretreatments. Our data showed that the advantages of the new pretreatment include higher carbohydrate recovery, no inhibitor production, and lower energy consumption. The new pretreatment development mimicking natural system could be useful for biochemical conversion of algal biomass to fuels and chemicals. PMID- 26677398 TI - Characterization of lignin derived from water-only and dilute acid flowthrough pretreatment of poplar wood at elevated temperatures. AB - BACKGROUND: Flowthrough pretreatment of biomass is a critical step in lignin valorization via conversion of lignin derivatives to high-value products, a function vital to the economic efficiency of biorefinery plants. Comprehensive understanding of lignin behaviors and solubilization chemistry in aqueous pretreatment such as water-only and dilute acid flowthrough pretreatment is of fundamental importance to achieve the goal of providing flexible platform for lignin utilization. RESULTS: In this study, the effects of flowthrough pretreatment conditions on lignin separation from poplar wood were reported as well as the characteristics of three sub-sets of lignin produced from the pretreatment, including residual lignin in pretreated solid residues (ReL), recovered insoluble lignin in pretreated liquid (RISL), and recovered soluble lignin in pretreatment liquid (RSL). Both the water-only and 0.05 % (w/w) sulfuric acid pretreatments were performed at temperatures from 160 to 270 degrees C on poplar wood in a flowthrough reactor system for 2-10 min. Results showed that water-only flowthrough pretreatment primarily removed syringyl (S units). Increased temperature and/or the addition of sulfuric acid enhanced the removal of guaiacyl (G units) compared to water-only pretreatments at lower temperatures, resulting in nearly complete removal of lignin from the biomass. Results also suggested that more RISL was recovered than ReL and RSL in both dilute acid and water-only flowthrough pretreatments at elevated temperatures. NMR spectra of the RISL revealed significant beta-O-4 cleavage, alpha-beta deoxygenation to form cinnamyl-like end groups, and slight beta-5 repolymerization in both water-only and dilute acid flowthrough pretreatments. CONCLUSIONS: Elevated temperature and/or dilute acid greatly enhanced lignin removal to almost 100 % by improving G unit removal besides S unit removal in flowthrough system. Only mild lignin structural modification was caused by flowthrough pretreatment. A lignin transformation pathway was proposed to explain the complexity of the lignin structural changes during hot water and dilute acid flowthrough pretreatment.Graphical abstractLignin transformations in water-only and dilute acid flowthrough pretreatment at elevated temperatures. PMID- 26677399 TI - Toward a Genetic Understanding of Glaucoma-Breakthroughs and Challenges from Studies of Exfoliation Glaucoma. PMID- 26677400 TI - Core 2 mucin-type O-glycan inhibits EPEC or EHEC O157:H7 invasion into HT-29 epithelial cells. AB - BACKGROUND: How host cell glycosylation affects EPEC or EHEC O157:H7 invasion is unclear. This study investigated whether and how O-glycans were involved in EPEC or EHEC O157:H7 invasion into HT-29 cells. RESULTS: Lectin histochemical staining confirmed stronger staining with PNA, which labeled Galbeta1, 3 GalNAc (core 1 structure) in HT-29-Gal-OBN and C2GnT2-sh2/HT-29 cells, compared with control cells. EPEC or EHEC O157:H7 invasion into HT-29 and its derived cells was based on the intracellular presence of GFP-labeled bacteria. The differentiation of HT 29 cells led to a reduction in EPEC internalization compared with HT-29 cells (p < 0.01). EPEC or EHEC O157:H7 invasion into HT-29-OBN and HT-29-Gal-OBN cells increased compared with HT-29 and HT-29-Gal cells (p < 0.05 and p < 0.01). Core 2 O-glycan-deficient HT-29 cells underwent a significant increase in EPEC (p < 0.01) or EHEC O157:H7 (p < 0.05) invasion compared with control cells. METHODS: Bacterial invasion into cultured cells was determined by a gentamicin protection assay and a GFP-labeled bacteria invasion assay. O-glycans biosynthesis was inhibited by benzyl-alpha-GalNAc, and core 2 O-glycan-deficient HT-29 cells were induced by C2GnT2 interference. CONCLUSION: These data indicated that EPEC or EHEC O157:H7 invasion into HT-29 cells was related to their O-glycosylation status. This study provided the first evidence of carbohydrate-dependent EPEC or EHEC O157:H7 invasion into host cells. PMID- 26677396 TI - Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study). AB - BACKGROUND: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. METHODS: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. RESULTS: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. CONCLUSIONS: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions. PMID- 26677401 TI - MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma-a step towards personalized therapy. AB - BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is defined as a pulmonary adenocarcinoma with a predominant component of intestinal differentiation and tumor cells positive for at least one intestinal marker. The aim of the present study was the molecular and histological characterization of a PEAC from a patient with two other family members affected by similar lung tumors, which has never been reported before. FINDINGS: We evaluated the molecular characteristics of the proband's PEAC by using a previously validated 47-microRNA (miRNA) cancer-specific array and a predictive method to estimate tissue-of-origin probabilities. Immunohistochemical (IHC) staining for thyroid transcription factor (TTF-1), napsin A, caudal-related homeobox 2 (CDX2), cytokeratins, and mucins, as well as mutational analyses for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) were performed on formalin-fixed, paraffin embedded (FFPE) tissues. The occurrence of PEAC in two family members was associated with similar clinicopathological features (age at diagnosis, smoking habit, tumor localization, multiple colonic polyps), histologic findings (TTF-1 negativity and CDX2 positivity), and genetic findings (KRAS (Gly12Asp) mutation, but no EGFR/ALK aberrations). miRNA profiling revealed similarities with non small cell lung cancer (NSCLC; 75.98 %) and some overlap with pancreatic ductal adenocarcinoma (PDAC; 23.34 %), but not with colorectal cancer (CRC; less than 0.5 %). Notably, these PEACs share key PDAC-associated miRNAs associated with tumor aggressiveness (miR-31*/-126*/-506/-508-3p/-514). CONCLUSIONS: We describe for the first time PEAC in members from the same family, associated with similar clinical and genetic features. miRNA profiling of the PEAC resembled a NSCLC signature, with partial overlap to a PDAC pattern. This could explain its aggressive behavior and therefore help to guide future tailored-therapeutic approaches. PMID- 26677402 TI - Orthogonal Matrix Retrieval In Cryo-Electron Microscopy. AB - In single particle reconstruction (SPR) from cryo-electron microscopy (EM), the 3D structure of a molecule needs to be determined from its 2D projection images taken at unknown viewing directions. Zvi Kam showed already in 1980 that the autocorrelation function of the 3D molecule over the rotation group SO(3) can be estimated from 2D projection images whose viewing directions are uniformly distributed over the sphere. The autocorrelation function determines the expansion coefficients of the 3D molecule in spherical harmonics up to an orthogonal matrix of size (2l + 1) * (2l + 1) for each l = 0,1,2,.... In this paper we show how techniques for solving the phase retrieval problem in X-ray crystallography can be modified for the cryo-EM setup for retrieving the missing orthogonal matrices. Specifically, we present two new approaches that we term Orthogonal Extension and Orthogonal Replacement, in which the main algorithmic components are the singular value decomposition and semidefinite programming. We demonstrate the utility of these approaches through numerical experiments on simulated data. PMID- 26677403 TI - Computational Modeling of Kinase Inhibitor Selectivity. AB - An exhaustive computational exercise on a comprehensive set of 15 therapeutic kinase inhibitors was undertaken to identify as to which compounds hit which kinase off-targets in the human kinome. Although the kinase selectivity propensity of each inhibitor against ~480 kinase targets is predicted, we compared our predictions to ~280 kinase targets for which consistent experimental data are available and demonstrate an overall average prediction accuracy and specificity of ~90%. A comparison of the predictions was extended to an additional ~60 kinases for sorafenib and sunitinib as new experimental data were reported recently with similar prediction accuracy. The successful predictive capabilities allowed us to propose predictions on the remaining kinome targets in an effort to repurpose known kinase inhibitors to these new kinase targets that could hold therapeutic potential. PMID- 26677404 TI - Triazolo Derivatives as Inhibitors of PDE10A. PMID- 26677405 TI - d-Amino Acid Oxidase Inhibitors: Potential Therapy for Schizophrenia. PMID- 26677406 TI - Autotaxin Inhibitors May Treat Pain and Osteoarthritis. PMID- 26677407 TI - A2A Receptor Antagonists May Potentially Treat Parkinson's Disease. PMID- 26677408 TI - Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder. AB - BACKGROUND: Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain's wiring diagram, i.e., the connectome. METHODS: We acquired diffusion-weighted magnetic resonance imaging data from 14 adult males with high-functioning ASD and 19 age-, gender-, and IQ-matched controls. As with diffusion tensor imaging-based tractography, it is not possible to detect complex (e.g., crossing) fiber configurations, present in 60-90 % of white matter voxels; we performed constrained spherical deconvolution-based whole brain tractography. Unweighted and weighted structural brain networks were then reconstructed from these tractography data and analyzed with graph theoretical measures. RESULTS: In subjects with ASD, global efficiency was significantly decreased both in the unweighted and the weighted networks, normalized characteristic path length was significantly increased in the unweighted networks, and strength was significantly decreased in the weighted networks. In the local analyses, betweenness centrality of the right caudate was significantly increased in the weighted networks, and the strength of the right superior temporal pole was significantly decreased in the unweighted networks in subjects with ASD. CONCLUSIONS: Our findings provide new insights into understanding ASD by showing that the integration of structural brain networks is decreased and that there are abnormalities in the connectivity of the right caudate and right superior temporal pole in subjects with ASD. PMID- 26677409 TI - Mitochondria can orchestrate sex differences in cell fate of vascular smooth muscle cells from rats. AB - BACKGROUND: In basal conditions, vascular smooth muscle cells freshly isolated from aortas of male and female rats display marked sex differences in terms of redox balance and susceptibility to ultraviolet radiation-induced cell death. In particular, in the same experimental conditions, cells from male rats are more susceptible to oxidative stress and underwent apoptosis, while cells from female rats underwent premature senescence. In the present work, the mechanism involved in cell fate after ultraviolet radiation exposure is investigated. METHODS: Vascular smooth muscle cells, isolated from the descending aortas of both female and male Sprague-Dawley young rats, were exposed to a single sub-cytotoxic dose of ultraviolet radiation (200 mJ/cm(2)). The distribution and the expression of molecules involved in cell survival and mitochondrial physiology were evaluated by static and flow cytometry using commercial kits and antibodies. Statistical analyses were performed by using Student's t test and two-way ANOVA. RESULTS: After exposure to ultraviolet radiation, an upregulation of survival proteins such as BclxL, survivin and the presence in the nucleus of NF-kappaB were found in cells from females. Conversely, pro-apoptotic proteins such as Bax, caspase-3, and caspase-9 as well as loss of mitochondrial membrane potential were found in cells from male rats. CONCLUSIONS: Our results suggest that (i) mitochondria, being producers of ROS, can orchestrate sex differences in cell fate of VSMC and (ii) mitochondrial dysfunction may be a significant mechanism by which cardiovascular risk factors lead to the formation of vascular lesions in a sex specific way. PMID- 26677410 TI - The incidence of un-indicated preoperative testing in a tertiary academic ambulatory center: a retrospective cohort study. AB - BACKGROUND: Despite existing evidence and guidelines advocating for appropriate risk stratification, ambulatory surgery in low-risk patients continues to be accompanied by a battery of routine tests prior to surgery. Using a single-center retrospective cohort study, we aimed to quantify the incidence of un-indicated preoperative testing in an academic ambulatory center by utilizing recommendations by the recently developed American Society of Anesthesiology (ASA) "Choosing Wisely" Top-5 list. METHODS: We utilized data from the EPIC medical records of 3111 patients who had ambulatory surgery at the Hospital of the University of Pennsylvania during a 6-month period. Data were abstracted from laboratory studies- complete blood count, electrolyte panel, coagulation studies, and cardiac studies-stress test, and echocardiogram obtained within 30 days prior to surgery. Preoperative tests obtained from each patient were categorized into "indicated" (ASA >= 3) and "un-indicated" (ASA 1 and 2) tests, and percentages were reported. RESULTS: During the study period, 52.9 % (95 % confidence interval (CI) 37.6-66.4) of all patients had at least one un-indicated laboratory test performed preoperatively. Further analysis revealed variation in the incidence of preoperative ordering between tests; 73 % of all complete blood counts (CBCs), 70 % of all metabolic panels, and 49 % of all coagulation studies were considered un indicated by "Top-5 List" criteria. Stated differently, of the patients included in the sample, 51 % of patients received an un-indicated CBC, 41 % an un indicated metabolic panel, and 16 % un-indicated coagulation studies. Twelve percent of "any un-indicated preoperative test" were obtained from ASA 1 healthy patients. Of the 587 patients less than 36 years old, 331 (56 %) had at least one test that was deemed un-indicated. Forty-one patients had either an echocardiogram or stress test ordered and performed within 30 days of surgery. Of these, eight (19.5 %) studies were un-indicated as determined by chart review. CONCLUSIONS: The incidence of ordering "at least one un-indicated preoperative test" in low-risk patients undergoing low-risk surgery remains high even in academic tertiary institutions. In the emerging era of optimizing patient safety and financial accountability, further studies are needed to better understand the problem of overuse while identifying modifiable attitudes and institutional influences on perioperative practices among all stakeholders involved. Such information would drive the development of feasible interventions. PMID- 26677411 TI - SCOFF in a general swedish adolescent population. AB - BACKGROUND: Although Disordered Eating Behaviors (DEB) is an ill-defined concept, multiple studies have examined prevalence of DEB and its relations to other variables in various populations. DEB have been shown to predict more serious eating disorders which in turn can lead to death. Mostly girls seem to suffer from DEB, but the question has been raised whether this, at least, partially is due to the methods used for screening. The SCOFF-questionnaire has been suggested as a quick and easily administered tool to assess DEB. However, the psychometric results regarding SCOFF suggest some inconsistencies, and more research is needed in various countries and age samples. METHOD: To validate SCOFF, a total of 1265 Swedish adolescents (51.6 % girls) completed self-report questionnaires using the Eating Disorder Examination Questionnaire (EDE-Q) as a reference standard. RESULTS: The factor analyses show inconclusive results as to whether SCOFF should be regarded as a comprehensive scale; furthermore, the results indicate a correlation between SCOFF and the EDE-Q in both girl and boy samples. Girls scored significantly higher on SCOFF and also had a higher total score, indicating more severe problems than boys. CONCLUSIONS: The results raised questions as to whether the SCOFF might be interpreted and responded to in different ways by girls and boys, risking overlooking boys' DEB and also whether one "yes" answer, instead of the stipulated two, could be sufficient when using SCOFF for screening purposes. In sum, the results challenge the use of SCOFF in a general adolescent population. PMID- 26677412 TI - Overvaluation of shape and weight in adolescents with anorexia nervosa: does shape concern or weight concern matter more for treatment outcome? AB - BACKGROUND: Overvaluation of shape and weight is a key diagnostic feature of anorexia nervosa (AN); however, limited research has evaluated the clinical utility of differentiating between weight versus shape concerns. Understanding differences in these constructs may have important implications for AN treatment given the focus on weight regain. This study examined differences in treatment outcome between individuals whose primary concern was weight versus those whose primary concern was shape in a randomized controlled trial of treatment for adolescent AN. METHODS: Data were drawn from a two-site randomized controlled trial that compared family-based treatment and adolescent focused therapy for AN. Chi-square tests and logistic regression analyses were conducted. RESULTS: Thirty percent of participants presented with primary weight concern (n = 36; defined as endorsing higher Eating Disorder Examination (EDE) Weight Concern than Shape Concern subscale scores); 60 % presented with primary shape concern (n = 72; defined as endorsing higher EDE Shape Concern than Weight Concern scores). There were no significant differences between the two groups in remission status at the end of treatment. Treatment did not moderate the effect of group status on achieving remission. CONCLUSIONS: Results suggest that treatment outcomes are comparable between adolescents who enter treatment for AN with greater weight concerns and those who enter treatment with greater shape concerns. Therefore, treatment need not be adjusted based on primary weight or primary shape concerns. PMID- 26677414 TI - Spinocerebellar ataxia 28: a novel AFG3L2 mutation in a German family with young onset, slow progression and saccadic slowing. AB - BACKGROUND: Spinocerebellar ataxia type 28 (SCA28) is related to mutations of the ATPase family gene 3-like 2 gene (AFG3L2). To date, 13 private missense mutations have been identified in families of French, Italian, and German ancestry, but overall, the disorder seems to be rare in Europe. Here, we report a kindred of German ancestry with four affected family members presenting with slowly progressive ataxia, mild pyramidal tract signs and slow saccades. METHODS: After excluding repeat expansions in the genes for SCA1-3, 6-8, 10, 12, and 17, Sanger sequencing of the coding regions of TTBK2 (SCA11), KCNC3 (SCA13), PRKCG (SCA14), FGF14 (SCA27) and AFG3L2 (SCA28) was performed. The 17 coding exons of AFG3L2 with flanking intronic sequences were amplified by PCR and sequenced on both strands. RESULTS: Sequencing detected a novel potential missense mutation (p.Y689N) in the C-terminal proteolytic domain, the mutational hotspot of AFG3L2. The online programme "PolyPhen-2" classifies this amino acid exchange as probably damaging (score 0.990). Similarly to most of the published SCA28 mutations, the novel mutation is located within exon 16. Mutations in exon 16 alter the proteolytic activity of the protease AFG3L2 that is highly expressed in Purkinje cells. CONCLUSIONS: Genetic testing should be considered in dominant ataxia with pyramidal tract signs and saccadic slowing. PMID- 26677413 TI - Evaluation and management of lead exposure. AB - Lead, which is widely used in industry, is a common element found in low concentrations in the Earth's crust. Implementations to reduce environmental lead concentrations have resulted in a considerable reduction of lead levels in the environment (air) and a sustained reduction in the blood lead levels of the average citizen. However, people are still being exposed to lead through a variety of routes in everyday commodities. Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. Having a carcinogenic risk as well, the IARC classifies inorganic lead compounds as probably carcinogenic to humans (Group 2A). Occupational lead poisonings have decreased due to the efforts to reduce the lead concentrations in the working environment. In contrast, health hazards associated with long-term environmental exposure to low concentrations of lead have been reported steadily. In particular, chronic exposure to low concentrations of lead has been reported to induce cognitive behavioral disturbances in children. It is almost impossible to remove lead completely from the human body, and it is not easy to treat health hazards due to lead exposure. Therefore, reduction and prevention of lead exposure are very important. We reviewed the toxicity and health hazards, monitoring and evaluation, and management of lead exposure. PMID- 26677415 TI - Carotid body tumor imitator: An interesting case of Castleman's disease. AB - BACKGROUND: There are very few reports in the literature of Castleman's disease affecting the carotid artery and a single previous report of a case of Castleman's disease of the neck originally mistaken as a carotid body tumor. CASE DESCRIPTION: We describe a rare case of Castleman's disease, manifesting with classic radiographic hallmarks of a carotid body tumor. The postoperative pathologic examination identified the resected mass as Castleman's lymphadenopathy. The management of this particular case is discussed, and the findings are highlighted. CONCLUSIONS: We present a unique case of a tumor initially and incorrectly diagnosed as a carotid body tumor. However, after comprehensive treatment with endovascular and surgical modalities and subsequent pathologic examination, the diagnosis of this rare entity was made. PMID- 26677416 TI - Stent-assisted coil embolization for anterior cerebral artery dissection presented with cerebral infarction. AB - BACKGROUND: Compared to those found in the vertebrobasilar system, intracranial dissection in the anterior circulation is relatively rare, especially in the anterior cerebral artery (ACA). Moreover, only several cases of ACA dissection that underwent endovascular treatment have been reported. Here we present a rare case of gradually developing ACA dissecting aneurysm causing cerebral infarction, successfully treated by stent-assisted coil embolization. CASE DESCRIPTION: A 36 year-old man was admitted with sudden right hemiparesis. Diffusion-weighted magnetic resonance (MR) imaging showed cerebral infarction in the left ACA territory, and MR angiography showed segmental stenosis at the A2 portion of the left ACA. Three-dimensional digital subtraction angiogram showed segmental dilatation and stenosis at the left A2 portion. We diagnosed ACA dissection causing acute cerebral infarction and treated the patient conservatively. Five months after the onset, the dissecting artery at the left A2 portion formed a gradually dilating aneurysm, suggesting increased risk for aneurysmal rupture. We attempted endovascular treatment entailing coil embolization of an aneurysm while preserving the left A2 with stent assistance. The patient remained neurologically stable 6 months after the procedure. CONCLUSIONS: Although there are few reported cases of ACA dissection where endovascular treatment was attempted, we consider stent-assisted embolization for gradually developing ACA dissecting aneurysm as an alternative method to prevent bleeding and recurrent infarction. PMID- 26677417 TI - Neuroethics scope at a glance. AB - The term neuroethics defines the bioethics field that deals with the dilemmas arising from the development of the neurosciences. Why are we so sensitive to ponder on neuroethics? Because it involves the brain, the organ responsible for our perceptions, our thoughts, and our conscience; and its knowledge and/or manipulation entail the most genuine and nontransferable aspects of the human being. Since 2002, neuroethics has been recognized as a new discipline that offers an area of consideration for neuroscientific knowledge and the actions regarding human beings as individuals, and the society as an organization. Within its framework, we can distinguish two branches: fundamental neuroethics and applied neuroethics. Neuroethics demands that we are on alert, and we offer the possibility of interdisciplinary exchange programs, encouraging society to participate, promoting the ethical opinions, and even working with anticipation on the dilemmas that are already emerging. Science does not stop, and its development has acquired such an accelerated pace that there has not been enough time to discuss its processes. We are convinced that neuroethics will be for the 21(st) century, what genetics was for the 20(th) century. PMID- 26677418 TI - Bioethics - should they encourage the killing of unwanted newborn infants? PMID- 26677419 TI - Surgical management of ruptured small cerebral aneurysm: Outcome and surgical notes. AB - BACKGROUND: Management of small aneurysms often poses a therapeutic dilemma and surgical treatment or coiling can be considered as therapeutic choices. In the present study, we reviewed our series of ruptured small cerebral aneurysm treated surgically. METHODS: A total of 53 consecutive patients with ruptured small aneurysm were surgically treated between January 2008 and July 2014. Data were retrospectively collected. Procedure-related death and complications were systematically reviewed. Clinical outcomes were assessed using the Modified Ranking Scale. Neuroradiological follow-up was performed to assess aneurysmal occlusion and recanalization rate. RESULTS: The mean aneurysm size was 2 mm +/- 0.8 mm. All the patients were operated and the aneurysm clipped. Clinical outcomes were as expected on the basis of the presenting Hunt and Hess grade. Overall, major and minor neurological deficit related to clipping were 5.2% and 2.2%, respectively. At the time of discharge, 84.9% of the patients presented with a favorable outcome, while 15.1% had poor clinical outcome. Aneurysm occlusion was achieved in all the cases. Neither recanalization nor re-aneurysmal rupture was observed in the clinical follow-up. CONCLUSION: Aneurysms, 3 mm in diameter or smaller, represent a therapeutic challenge. Given the proven role of microsurgery in small aneurysms and the perceived challenges with endovascular therapy, surgical clipping still can be considered an effective treatment modality in this setting. PMID- 26677420 TI - Osteoarthritis of the Manubriosternal Joint: An Uncommon Cause of Chest Pain. AB - Osteoarthritis of the manubriosternal joint is a rare cause of chest pain. The diagnosis is difficult, and other serious causes of chest pain have to be ruled out first. We report one case that was treated with fusion of the manubriosternal joint using an iliac crest bone graft with a cervical locking plate and screws with excellent results. Preoperative CT scan images were used to measure the screw length and the drill stop depth. In this case report, we have shown that arthrodesis can be an effective way of treating osteoarthritis of the manubriosternal joint when other measures fail. Furthermore, the use of a cervical locking plate with appropriate and careful preoperative planning affords a safe surgical technique, rapid pain relief, and ultimately, sound and asymptomatic union of the joint. PMID- 26677421 TI - Writing Technical Reports for Simulation in Education for Health Professionals: Suggested Guidelines. AB - Simulation is an important training tool used in a variety of influential fields. However, development of simulation scenarios - the key component of simulation - occurs in isolation; sharing of scenarios is almost non-existent. This can make simulation use a costly task in terms of the resources and time and the possible redundancy of efforts. To alleviate these issues, the goal is to strive for an open communication of practice (CoP) surrounding simulation. To facilitate this goal, this report describes a set of guidelines for writing technical reports about simulation use for educating health professionals. Using an accepted set of guidelines will allow for homogeneity when building simulation scenarios and facilitate open sharing among simulation users. In addition to optimizing simulation efforts in institutions that are currently using simulation as an educational tool, the development of such a repository may have direct implications on developing countries, where simulation is only starting to be used systematically. Our project facilitates equivalent and global access to information, knowledge, and highest-caliber education - in this context, simulation - collectively, the building blocks of optimal healthcare. PMID- 26677423 TI - Computer-Assisted Navigation During an Anterior-Posterior En Bloc Resection of a Sacral Tumor. AB - Previously, a computer-based navigation system has not been used routinely for en bloc resection of sacral tumors. In order to improve the accuracy of tumor resection, O-arm navigation was used to join anterior and posterior osteotomies during an en-bloc resection of a sacral Ewing's sarcoma. This case study describes the technique for en-bloc resection of a sacral Ewing's sarcoma guided by O-arm computer navigation and intraoperative neurophysiological monitoring (IONM). An 18-year-old male presented with weakness in his left lower extremity. MRI of the patient's spine showed a sacral mass causing compression of left S1 and S2 roots. A surgical resection was planned with anterior and posterior approaches. An O-arm computer navigation system was used to assist in meeting anterior osteotomy cuts with the posterior cuts to ensure complete resection of the sacral tumor with a safe margin. Computer-assisted navigation was used along with IONM during this procedure to help guide the surgical team in an adequate tumor resection. There were no complications related to the use of the O-arm or the navigation system. Computer navigation guidance is both useful and safe in sacral tumor resections. It enhanced the accuracy of the en-bloc removal of a sacral tumor with safe margins while protecting neural function and minimizing recurrence. PMID- 26677422 TI - Improving Brain Tumor Research in Resource-Limited Countries: A Review of the Literature Focusing on West Africa. AB - Neoplasms of the brain are often overlooked in resource-limited countries. Our literature search via AJOL and PubMed demonstrated that brain tumor research is still a rarity in these regions. We highlight the current status, importance, challenges, and methods of improving brain tumor research in West Africa. We suggest that more attention be given to basic, clinical, and epidemiological brain tumor research by national governments, private organizations, international organizations, non-governmental organizations (NGOs), and individuals in this region. PMID- 26677424 TI - Bacterial Colony: First Report of Donut Colony Morphology among Diphtheroids Isolated in Blood. AB - Isolation of diphtheroids in human clinical specimens is not uncommon. Several studies have highlighted the significance of these bacteria in human infection, which morphologically resemble Corynebacterium diphtheriae. Previous studies have noted that occurrence of these bacteria in specimens like the blood should not be ignored as they can result in serious infections like endocarditis and sepsis among debilitated individuals, including the neonates. We report isolation of diphtheroid bacterium in blood from a case of septicaemia showing donut colony morphology. PMID- 26677425 TI - Can Aliskiren be Considered as a New Novel Drug for Hypertension? AB - Hypertension is one of the most common causes of death across the globe. Many trials and drugs have been used for controlling the debilitating effects of hypertension. One such new class of drug is direct renin inhibitors (DRI), e.g., aliskiren, which block the renin-angiotensin system (RAS). It blocks the very first step in the RAS system. Multiple trials have been carried out debating the outcome of monotherapy and combination therapy with other classes of hypertensive drugs. Focus on compliance, adverse effects, and the cost have also been in the news. Extensive studies are still needed to justify the clinical use of a DRI in the effective treatment of hypertension. PMID- 26677426 TI - Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets. AB - The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID- 26677427 TI - Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology. AB - There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application. PMID- 26677429 TI - Neuroendocrine tumors resistant to mammalian target of rapamycin inhibitors: A difficult conversion from biology to the clinic. AB - Deregulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) - mammalian target of rapamycin (mTOR) signaling pathway is one of the most commonly-involved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors (NETs). mTOR inhibitors used in clinical practice are derived from rapamycin, an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin derived mTOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderately-differentiated pancreatic NETs (pNETs). It inhibits specifically the mTORC1 subunit of mTOR, not interacting with mTORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with pNETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to mTOR inhibitors are Akt and PI3K activation, by means of mTORC2 and insulin growth factor (IGF) - IGF receptor signaling, respectively. BEZ235 is a multi-targeted inhibitor binding to PI3K, mTORC1 and mTORC2, therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in pNETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase I step of clinical development and the design of phase II clinical trials. PMID- 26677428 TI - Current role of spacers for prostate cancer radiotherapy. AB - Radiotherapy is an established curative treatment method for prostate cancer. Optimal tumor control rates can only be achieved with high local doses, associated with a considerable risk of rectal toxicity. Apart from already widely adapted technical advances, as intensity-modulated radiation therapy, the application of spacers placed between the prostate and rectum has been increasingly used in the last years. Biodegradable spacers, including hydrogel, hyaluronic acid, collagen or an implantable balloon, can be injected or inserted in a short procedure under transrectal ultrasound guidance via a transperineal approach. A distance of about 1.0-1.5 cm is usually achieved between the rectum and prostate, excluding the rectal wall from the high isodoses. Several studies have shown well tolerated injection procedures and treatments. Apart from considerable reduction of rectal irradiation, a prospective randomized trial demonstrated a reduction of rectal toxicity after hydrogel injection in men undergoing prostate image-guided intensity-modulated radiation therapy. The results are encouraging for continuing evaluation in dose escalation, hypofractionation, stereotactic radiotherapy or re-irradiation trials in the future. PMID- 26677430 TI - Inorganic phosphate in the development and treatment of cancer: A Janus Bifrons? AB - Inorganic phosphate (Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism, kinase/phosphatase signaling and in the formation and function of lipids, carbohydrates and nucleic acids and, at systemic level, it plays a key role for normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient, minimally regulated and typically extends to approximately 70%. Maintenance of proper Pi homeostasis is a critical event and serum Pi level is maintained within a narrow range through an elaborate network of humoral interactions and feedback loops involving intestine, kidney, parathyroid gland and bone, and depends on the activity of a number of hormones, including parathyroid hormone, 1,25-dihydroxy vitamin D, and fibroblast growth factor 23 as major regulators of Pi homeostasis. Notably, Pi intake seemingly continues to increase as a consequence of chronic high-phosphorus (P) diets deriving from the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. Several recent reports have generated significant associations between high-P intake or high-serum Pi concentration and morbidity and mortality. Many chronic diseases, including cardiovascular diseases, obesity and even cancer have been proposed to be associated with high-P intakes and high-serum Pi concentrations. On the other hand, there is also evidence that Pi can have antiproliferative effects on some cancer cell types, depending on cell status and genetic background and achieve additive cytotoxic effects when combined with doxorubicin, illustrating its potential for clinical applications and suggesting that up-regulating Pi levels at local sites for brief times, might contribute to the development of novel and cheap modalities for therapeutic intervention in some tumours. Overall, the influence of Pi on cell function and the possible relationship to cancer have to be fully understood and investigated further. PMID- 26677431 TI - Sentinel lymph node metastasis after neoadjuvant treatment in breast cancer: Any size matters? AB - One of the advantages of neoadjuvant chemotherapy (NAC) treatments is its ability to convert patients who need a mastectomy in breast conservative surgery. NAC has also increased the conversion of node positive patients into node negative in around 40% allowing the use of sentinel node biopsy (SLN) in this setting. Timing of SLN biopsy after NAC has been a subject of debate. In patients with clinically node negative before NAC, rates of success and false negative rates of SLN after NAC are similar to those in the adjuvant setting, so SLN after NAC in previous negative axilla has been incorporated in the staging of the axilla. More controversial is its use in patients with positive axillary nodes before NAC who convert to node negative after NAC. Several randomized studies have reported the identification rates and the false negative rates of the SLN after NAC, concordant in the importance of surgical technique. As there is an agreement in the abandon of the immunohistochemistry (IHC) for SLN in the adjuvant setting as SLN IHC detected metastasis appear to have no impact on overall survival, in patients with SLN after NAC the inclusion of isolated tumor cell (ITC) as positive nodes lowers the false negative rates of the technique, suggesting the importance of assessing the SLN by IHC after NAC and considering it as residual disease. Longer follow up is needed to determine the prognostic implications of ITC in the SLN after NAC. PMID- 26677432 TI - Microenvironment and endocrine resistance in breast cancer: Friend or foe? AB - Breast cancer affects one in eight women around the world. Seventy five percent of these patients have tumors that are estrogen receptor positive and as a consequence receive endocrine therapy. However, about one third eventually develop resistance and cancer reappears. In the last decade our vision of cancer has evolved to consider it more of a tissue-related disease than a cell-centered one. This editorial argues that we are only starting to understand the role the tumor microenvironment plays in therapy resistance in breast cancer. The development of new therapeutic strategies that target the microenvironment will come when we clearly understand this extremely complicated scenario. As such, and as a scientific community, we have extremely challenging work ahead. We share our views regarding these matters. PMID- 26677433 TI - Combination therapies improve the anticancer activities of retinoids in neuroblastoma. AB - Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index, and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy, death still occurs due to relapse of persistent minimal residual disease (MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma (NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD, yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies, with a lower side effect profile, are required to improve outcomes for NB. Fenretinide or N-4 hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and -independent signalling mechanisms. Moreover, several histone deacetylase inhibitors have entered early phase trials, and, suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies. PMID- 26677434 TI - Direct therapeutic intervention for advanced pancreatic cancer. AB - Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID- 26677435 TI - Tumor biology in estrogen receptor-positive, human epidermal growth factor receptor type 2-negative breast cancer: Mind the menopausal status. AB - Breast cancer is not one disease, but can be categorized into four major molecular subtypes according to hormone receptor [estrogen receptor (ER) and progesterone receptor (PgR)] and human epidermal growth factor receptor type 2 (HER2) expression status. Ki67 labeling index and/or multigene assays are used to classify ER-positive, HER2-negative breast cancer into luminal A and luminal B (HER2-negative) subtypes. To date, most studies analyzing predictive or prognostic factors in ER-positive breast cancer have been performed in postmenopausal women, mainly using patients and samples in adjuvant aromatase inhibitor trials. In contrast, even the clinical roles of PgR and Ki67 have been little analyzed so far in premenopausal women. PgR is one of the estrogen responsive genes, and it has been reported that plasma estradiol levels are related to expression levels of estrogen-responsive genes including PGR in ER positive breast cancer. In this article, biological differences, especially differences in expression of PgR and Ki67 in ER-positive breast cancer between pre- and postmenopausal women are discussed. Clinical roles of PgR and Ki67 in ER positive breast cancer differ between pre- and postmenopausal women. We suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status. PMID- 26677436 TI - Adjuvant chemotherapy for rectal cancer: Is it needed? AB - Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID- 26677437 TI - Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract. AB - Lymphadenectomy for urothelial carcinoma of the upper urinary tract has attracted the attention of physicians. The mapping study of lymphatic spread has shown that a relatively wide area should comprise the regional nodes for tumors of the right renal pelvis or the right upper two-thirds of the ureter. A prospective study showed that an anatomical template-based lymphadenectomy significantly improved patient survival in tumors of the renal pelvis. This benefit was more evident for patients with pT2 stage tumors or higher. The risk of regional node recurrence is significant reduced by template-based lymphadenectomy, which is likely to be associated with improved patient survival. The removal of lymph node micrometastases is assumed to be the reason for therapeutic benefit following lymphadenectomy. The number of resected lymph nodes can be used to assess the quality of lymphadenectomy, but not to determine the extent of lymphadenectomy. The guidelines currently recommend lymphadenectomy for patients with muscle invasive disease, even though the current recommendation grades are still low. The present limitation of lymphadenectomy is the lack of standardization of the extent of lymphadenectomy and the randomized trials. Further studies are warranted to collect the evidence to support lymphadenectomy. PMID- 26677438 TI - Biomarkers in triple negative breast cancer: A review. AB - Breast cancer is an intrinsically heterogeneous disease. In the world about 1 million cases of breast cancer are diagnosed annually and more than 170000 are triple-negative. Characteristic feature of triple negative breast cancer (TNBC) is that it lacks expression of oestrogen, progesterone and human epidermal growth factor receptor-2/neu receptors. They comprise 15%-20% of all breast cancers. We did a systematic review of PubMed and conference databases to identify studies published on biomarkers in TNBC. We included studies with biomarkers including: Epidermal growth factor receptor, vascular endothelial growth factor, c-Myc, C kit and basal cytokeratins, Poly(ADP-ribose) polymerase-1, p53, tyrosinase kinases, m-TOR, heat and shock proteins and TOP-2A in TNBC. We also looked for studies published on synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. TNBC is a complex disease subtype with many subclasses. Majority TNBC have a basal-like molecular phenotype by gene expression profiling. Their clinical and pathologic features overlap with hereditary BRCA1 related breast cancers. Management of these tumours is a challenge to the clinician because of its aggressive behaviour, poor outcome, and absence of targeted therapies. As the complexity of this disease is being simplified over time new targets are also being discovered for the treatment of this disease. There are many biomarkers in TNBC being used in clinical practice. Biomarkers may be useful as prognostic or predictive indicators as well as suggest possible targets for novel therapies. Many targeted agents are being studied for treatment of TNBC. PMID- 26677439 TI - Dynamic role of myofibroblasts in oral lesions. AB - Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts (MFs). MFs are spindle-shaped cells with stress fibres and well-developed fibronexus, and they display alpha-smooth muscle actin immunohistochemically and smooth-muscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources, they play pivotal roles not only by synthesizing and producing extracellular matrix components, such as other connective tissue cells, but also are involved in force production. In the tissue remodelling phase of wound closure, integrin-mediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass, where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing, odontogenic cysts and tumours, salivary gland tumours, oral preneoplasia, and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer. PMID- 26677440 TI - Pelvic radiation disease: Updates on treatment options. AB - Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID- 26677443 TI - Carcinoma of unknown primary and paraneoplastic dermatomyositis. AB - Dermatomyositis is known to be associated with neoplastic disorders, however the presentation of carcinoma of unknown primary as dermatomyositis is rare. We describe a case index of 50-year-old female who presented with enlarged inguinal lymph nodes accompanied with symmetric proximal muscle weakness and erythematous plaques. Conventional basic work-up did not reveal the diagnosis, however, positron emission tomography-computed tomography and re-staining of the pathology specimen suggested the ovaries as the primary site. Chemotherapy including carboplatin paclitaxel and bevacizumab led to complete response of disease and improvement in the dermatomyositis. The present case emphasizes the importance of a thorough directed evaluation for the underlying cancer in patients with carcinoma of unknown primary presenting as dermatomyositis. We further provide an up-to-date detailed review of published data describing these clinical entities. PMID- 26677442 TI - Neoadjuvant chemotherapy followed by surgery in gastric cancer patients with extensive lymph node metastasis. AB - Gastric cancer with extensive lymph node metastasis (ELM) is usually considered unresectable and is associated with poor outcomes. Cases with clinical enlargement of the para-aortic lymph nodes and/or bulky lymph node enlargement around the celiac artery and its branches are generally dealt with as ELM. A standard treatment for gastric cancer with ELM has yet to be determined. Two phase II studies of neoadjuvant chemotherapy followed by surgery showed that neoadjuvant chemotherapy with S-1 plus cisplatin followed by surgical resection with extended lymph node dissection could represent a treatment option for gastric cancer with ELM. However, many clinical questions remain unresolved, including the criteria for diagnosing ELM, optimal regime, number of courses and extent of lymph node dissection. PMID- 26677441 TI - Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices. AB - Cervical cancer (CC) represents the fourth most common malignancy affecting women all over the world and is the second most common in developing areas. In these areas, the burden from disease remains important because of the difficulty in implementing cytology-based screening programmes. The main obstacles inherent to these countries are poverty and a lack of healthcare infrastructures and trained practitioners. With the availability of new technologies, researchers have attempted to find new strategies that are adapted to low- and middle-income countries (LMIC) to promote early diagnosis of cervical pathology. Current evidence suggests that human papillomavirus (HPV) testing is more effective than cytology for CC screening. Therefore, highly sensitive tests have now been developed for primary screening. Rapid molecular methods for detecting HPV DNA have only recently been commercially available. This constitutes a milestone in CC screening in low-resource settings because it may help overcome the great majority of obstacles inherent to previous screening programmes. Despite several advantages, HPV-based screening has a low positive predictive value for CC, so that HPV-positive women need to be triaged with further testing to determine optimal management. Visual inspection tests, cytology and novel biomarkers are some options. In this review, we provide an overview of current and emerging screening approaches for CC. In particular, we discuss the challenge of implementing an efficient cervical screening adapted to LMIC and the opportunity to introduce primary HPV-based screening with the availability of point-of-care (POC) HPV testing. The most adapted screening strategy to LMIC is still a work in progress, but we have reasons to believe that POC HPV testing makes part of the future strategies in association with a triage test that still needs to be defined. PMID- 26677444 TI - Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer. AB - AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine (FLX) in representative molecular subtypes of breast cancer. METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative (SUM149PT) and luminal (T47D and Au565) cancer cells and non-transformed MCF10A were investigated. Reverse phase protein microarray (RPPM) was performed with and without 10 MUmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10A. In comparison to the other lines, cell growth reduction in SUM149PT coincided with significant induction of endoplasmic reticulum (ER) stress and autophagy after 24 and 48 h of 10 MUmol/L FLX, resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker, cleaved microtubule-associated protein 1 light chain 3, in SUM149PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently, the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis, growth arrest at the G1 phase, autophagy, and caspase-7-mediated cell death. CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy, resulting in death of aggressive triple negative breast cancer SUM149PT. PMID- 26677445 TI - Facial nerve paralysis in children. AB - Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40% 75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID- 26677446 TI - Myasthenia gravis and thymic neoplasms: A brief review. AB - Thymoma is the most common mediastinal tumor. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. They have frequent association with various paraneoplastic syndromes (PNS). The most common PNS associated with thymoma is myasthenia gravis (MG). Patients of thymoma with MG have a favourable outcome due to early disclosure of the disease. Histologically they are classified into five subtypes and Masaoka-Koga staging system is used for staging. Surgery, chemotherapy and radiotherapy play an important role along with anti-myasthenia drugs. This review would like to highlight the association of thymoma with MG and associated clinical and therapeutic issues. PMID- 26677447 TI - Simultaneous Erb's and Klumpke's palsy: Case report. AB - Mapping nerve deficits during a physical exam after trauma to the upper extremity can help determine not only if the brachial plexus was injured but also which nerve roots were involved. A 28-year-old male presented with simultaneous signs and symptoms of Erb's (C5) and Klumpke's (C8, T1) palsy, with sparing of the C6 and C7 roots. The patient presented several months ago to his local emergency room with shortness of breath, which was determined to be caused by left diaphragmatic paralysis through clinical and radiographical evidence. However, the etiology of the current nerve dysfunction in the upper extremity remained unknown. With persistent questioning and establishing the patient's trust in the caregivers, it was revealed that the patient had attempted suicidal hanging. We describe the clinical features and the likely mechanism of injury leading to this previously unreported combination of brachial plexus injuries. The unique injuries to this patient's brachial plexus can be explained by the sequence of events during the attempted suicidal hanging. The upper brachial plexus was injured during the initial moments where the neck was excessively stretched and the lower brachial plexus was injured due to the patient reaching up and holding himself by his arm for an extended period of time. PMID- 26677448 TI - Sarcoma-associated sarcoid reaction: Report of cutaneous sarcoid reaction in a patient with liposarcoma. AB - Sarcoidosis is a systemic inflammatory condition in which noncaseating epithelioid cell granulomas appear within one or several body sites. Sarcoid reaction (also referred to as sarcoidal or sarcoid-like reaction) occurs in patients who do not fulfill the diagnostic criteria for systemic sarcoidosis but present with similar clinical and histological features. As sarcoma-associated sarcoid reactions are rare, we describe the features of sarcoid reaction that developed in a man with liposarcoma and summarize reports of other oncology patients with sarcoma-associated sarcoid reactions. A 68-year-old man with retroperitoneal liposarcoma presented for evaluation of erythematous dermal plaques on his left leg. Microscopic examination of a tissue specimen revealed multiple epithelioid granulomas in the superficial and mid-reticular dermis. Correlation of the clinical presentation and histopathologic findings established a diagnosis of liposarcoma-associated cutaneous sarcoid reaction. Sarcoid reactions have been described in only seven individuals with sarcoma, including two patients with leiomyosarcoma and one patient with either carcinosarcoma, Kaposi sarcoma, liposarcoma, malignant peripheral nerve sheath tumor, rhabdosarcoma, or synovial sarcoma. Sarcoidal granulomas most commonly develop within the locoregional draining lymph nodes. Sarcoid reactions may also affect other organs, such as the lungs, skin, and spleen. PMID- 26677449 TI - Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach. AB - Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared with that after 1 min. The presence of fluorescein in the mucosa was observed within a short time after local mucosal application of fluorescein, suggesting that pCLE images similarly to those after intravenous fluorescein administration can be acquired by local mucosal application of fluorescein. PMID- 26677450 TI - Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass. AB - IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography (CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as IgG4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. IgG4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of IgG4-RD is adjacent to multiple luminal organs. PMID- 26677451 TI - Probable case of drug reaction with eosinophilia and systemic symptom syndrome due to combination therapy with daclatasvir and asunaprevir. AB - A 66-year-old, interferon-ineligible, treatment-naive man who was diagnosed with chronic hepatitis C due to hepatitis C virus genotype 1b began combination therapy with daclatasvir and asunaprevir. On day 14 of treatment, hepatic reserve and renal function deterioration was observed, while his transaminase levels were normal. Both daclatasvir and asunaprevir were discontinued on day 18 of treatment, because the patient complained of dark urine and a rash on his trunk and four limbs. After discontinuing antiviral therapy, the abnormal laboratory finding and clinical manifestations gradually improved, without recurrence. Our case fulfilled the diagnostic criteria of probable drug reaction with eosinophilia and systemic symptom (DRESS) syndrome. Despite the 18-d treatment, sustained virological response 12 was achieved. Based on the clinical course, we concluded that there was a clear cause-and-effect relationship between the treatment and adverse events. To our knowledge, this patient represents the first case of probable DRESS syndrome that includes concomitant deterioration of hepatic reserve and renal function due to combination therapy with daclatasvir and asunaprevir, regardless of normalization of transaminase levels. Our case suggests that we should pay attention not only to the transaminase levels but also to allergic symptoms associated with organ involvement during combination therapy with daclatasvir and asunaprevir. PMID- 26677452 TI - Burkitt's lymphoma of maxillary gingiva: A case report. AB - Burkitt's lymphoma (BL) is an aggressive form of non-Hodgkin's B-cell lymphoma with three variants namely endemic, sporadic, and immunodeficiency-associated types. It is endemic in Africa and sporadic in other parts of the world. While the endemic form is widely reported to occur in early childhood and commonly involves the jaw bones, the sporadic form typically presents as an abdominal mass. This presentation reports a rare case of sporadic form of BL clinically manifesting as a generalized gingival enlargement in an immunocompetent adult male which demonstrated an aggressive behavior. The patient reported with a prominent anterior gingival swelling of 6 mo duration which slowly enlarged in size and associated with multiple lymph node involvement. Microscopic examination of the lesion using H, E and immunohistochemical diagnosis confirmed the diagnosis as BL. The patient succumbed to the disease before any therapy could be instituted. Since a wide array of causes can be attributed to gingival enlargements, it is necessary to consider malignancies as one of the important differential diagnosis so as to facilitate the need for appropriate diagnosis and prompt treatment. PMID- 26677453 TI - Unilateral neuropathic arthropathy of the shoulder secondary to syringomyelia: Diagnostic challenges. AB - Neuropathic arthropathy of the shoulder is a rare disorder characterized by joint degeneration, and is associated with loss of sensory innervation. Syringomyelia is a disease in which fluid-containing cavities (syrinxes) form within the spinal cord. Here, we report a case of neuropathic arthropathy of the shoulder secondary to syringomyelia in a 40-year-old woman. X-rays of the left shoulder revealed damage to bone and joint architecture. Blood tests indicated vitamin D deficiency and secondary hyperparathyroidism. Magnetic resonance imaging of the cervical spine showed a large syrinx from the second cervical spine to the second dorsal spine. Although neuropathic arthropathy is uncommon, it should be considered in cases of unexplained pain, discomfort, or limited range of motion of the affected joint. Symptoms related to the affected joint may precede or overshadow neurological deficits. Appropriate radiological examinations and diagnoses are imperative to prevent misdiagnosis or undetected bone and joint disorders. PMID- 26677454 TI - In vitro and in vivo antitumor activity of gemcitabine loaded thermosensitive liposomal nanoparticles and mild hyperthermia in pancreatic cancer. AB - The study was designed to explore the feasibility of increasing the delivery of gemcitabine-HCL (Gem), a poor membrane permeable and short half-life drug, through PEGylated thermosensitive liposomal nanoparticles (TSLnps) delivery system followed by mild hyperthermia (mTH) at 42 degrees C. In vitro release pattern of Gem-TSLnps showed a significant Gem release (60%, p<0.01) at 42 degrees C compared to that released at 37 degrees C (29%). Cell viability and clonogenic assay demonstrated significant inhibition of MiaPaCa-2 cells growth by Gem-TSLnps + mHT compared to Gem alone. Further, IC50 value of Gem treated cells was (0.077MUM) 1.2 fold higher compared to that treated with Gem-TSLnps + mHT (0.063 MUM). mHT treated cells showed moderate inhibition of cell growth compared to controls. For cellular uptake studies, flow cytometric analysis and confocal imaging revealed higher uptake of Rho-TSLnps compared to Rho-PE or untreated cells. Tumor volume of mice treated with Gem alone was 1.8 fold higher compared to the group treated with Gem-TSLnps + mHT. Further, tumor regression of Gem TSLnps + mHT treated group was significantly higher (p<0.01) compared to Gem TSLnps or Gem. No significant elevated liver enzymes were observed when serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of control group was compared to that of Gem or Gem-TSLnps+mHT treated groups. However, serum level of alkaline phosphatase (ALP) of Gem or Gem-TSLnps+ mHT treated group was significantly elevated (p<0.05) when compared to the control group. In conclusion, TSLnps increased the delivery of Gem to tumor cells and also enhanced significantly the antitumor activity of Gem when combined with heat. PMID- 26677455 TI - Prolonged Use of Oritavancin for Vancomycin-Resistant Enterococcus faecium Prosthetic Valve Endocarditis. AB - Oritavancin is a novel lipoglycopeptide with activity against Gram-positive organisms including streptococci, methicillin-resistant Staphylococcus aureus, vancomycin-resistant S aureus (VRSA), and vancomycin-resistant enterococci (VRE) [1-3]. The US Food and Drug Administration approved oritavancin as a single intravenous dose of 1200 mg for the treatment of acute bacterial skin and skin structure infections on the basis of 2 clinical trials demonstrating noninferiority compared with vancomycin [4, 5]. There are limited options for treatment of serious VRE infections. Monotherapy with daptomycin or tigecycline or linezolid may be sufficient in some cases, but combination therapy is often indicated for severe or complicated infections such as endocarditis. Several antibiotic combinations have been used in isolated case reports with some efficacy, including the following: high-dose ampicillin with an aminoglycoside [6], ampicillin with ceftriaxone or imipenem [7, 8], high-dose daptomycin with ampicillin and gentamicin [9] or with gentamicin and rifampin [10], daptomycin with tigecycline [11, 12], quinupristin-dalfopristin with high-dose ampicillin [13] or doxycycline and rifampin [14], and linezolid with tigecycline [15]. The limited efficacy, limited susceptibility, and extensive toxicities with many of these agents and combinations present barriers to effective treatment. Additional treatment options for VRE endocarditis would be valuable. Although oritavancin has been shown to have in vitro activity against some isolates of VRE, clinical data are lacking. We describe the first use of a prolonged course of oritavancin in the treatment of a serious VRE infection, prosthetic valve endocarditis. PMID- 26677456 TI - Epidemiology and Risk Factors for Echinocandin Nonsusceptible Candida glabrata Bloodstream Infections: Data From a Large Multisite Population-Based Candidemia Surveillance Program, 2008-2014. AB - Background. Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia. Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts population-based laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008 2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression. Results. Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6-1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2-5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0-3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0-6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure. Conclusion. The proportion of NS C glabrata isolates rose significantly during 2008-2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C glabrata without prior echinocandin exposure suggests possible transmission of resistant organisms. PMID- 26677457 TI - A Downward Trend of the Ratio of Influenza RNA Copy Number to Infectious Viral Titer in Hospitalized Influenza A-Infected Patients. AB - Background. Efficacy endpoints in influenza clinical trials may include clinical symptoms and virological measurements, although virology cannot serve as the primary endpoint. We investigated the relationship between influenza A RNA copy number and quantity of infectious viruses in hospitalized influenza patients. Methods. One hundred fifty influenza-infected, hospitalized patients were included in this prospective cohort study spanning the 2012-2013 influenza season. Daily nasopharyngeal samples were collected during hospitalization, and influenza A RNA copy number and infectious viral titer were monitored. Results. The decay rate for 50% tissue culture infectious dose (TCID50) was 0.51 +/- 0.14 log10 TCID50/mL per day, whereas the RNA copy number decreased at a rate of 0.41 +/- 0.04 log10 copies/mL per day (n = 433). The log ratio of the RNA copy number to the infectious viral titer within patient changes significantly with -0.25 +/- 0.09 units per day (P = .0069). For a 12-day observation period, the decay corresponds to a decline of this ratio of 3 log influenza RNA copies. Conclusions. Influenza RNA copy number in nasal swabs is co-linear with culture, although the rate of decay of cell culture-based viral titers was faster than that observed with molecular methods. The study documented a clear decreasing log ratio of the RNA copy number to the infectious viral titer of the patients over time. PMID- 26677458 TI - Focusing through dynamic tissue with millisecond digital optical phase conjugation. AB - Digital optical phase conjugation (DOPC) is a new technique employed in wavefront shaping and phase conjugation for focusing light through or within scattering media such as biological tissues. DOPC is particularly attractive as it intrinsically achieves a high fluence reflectivity in comparison to nonlinear optical approaches. However, the slow refresh rate of liquid crystal spatial light modulators and limitations imposed by computer data transfer speeds have thus far made it difficult for DOPC to achieve a playback latency of shorter than ~200 ms and, therefore, prevented DOPC from being practically applied to thick living samples. In this paper, we report a novel DOPC system that is capable of 5.3 ms playback latency. This speed improvement of almost 2 orders of magnitude is achieved by using a digital micromirror device, field programmable gate array (FPGA) processing, and a single-shot binary phase retrieval technique. With this system, we are able to focus through 2.3 mm living mouse skin with blood flowing through it (decorrelation time ~30 ms) and demonstrate that the focus can be maintained indefinitely-an important technological milestone that has not been previously reported, to the best of our knowledge. PMID- 26677459 TI - The History of Robotics in Surgical Specialties. PMID- 26677460 TI - Seasonal variations in nocturnal changes in blood pressure between Ireland and Singapore. AB - BACKGROUND: Normal blood pressure (BP) follows a circadian rhythm, with dipping of BP at night. However, knowledge is limited in how the nocturnal dipping in hypertensive patients changes with the seasons. The study aims to examine the pattern of seasonal changes of nocturnal dip in an Irish population and furthermore, to compare it to the pattern observed near the equator where such seasonal variations are minimal, by also studying a Singaporean population. METHODS: Ambulatory Blood Pressure Monitor recordings were obtained from 220 patients, half were from Mercy University Hospital, Cork, Ireland and half from the National Heart Centre, Singapore during the summer period from May to June and the winter period from October to December. RESULTS: Irish seasonal changes resulted in an increase in nocturnal dipping in the hypertensive patients, especially for diastolic pressure (95% CI, 0.72 to 6.03, 3.37mmHg; p<0.05) and a change in the duration of dipping at night (95% CI, 0.045 to 1.01, 0.53h; p < 0.05). In Singapore, slight differences in dipping in systolic pressure were apparent despite the presence of only minor alterations in temperature (95% CI, 0.38 to 4.83, 2.61mmHg; P<0.05) or duration of daylight. CONCLUSION: Seasonal changes not only affected the daily blood pressure but also the night time dipping status in hypertensive patients by mean value of 1.99mmHg and 3.38mmHg for systolic and diastolic pressure dip respectively. This has implications on how hypertensive patients should be treated during different seasons and when they are traveling to countries of different climatic environment. PMID- 26677461 TI - Towards Mobile OCR: How To Take a Good Picture of a Document Without Sight. AB - The advent of mobile OCR (optical character recognition) applications on regular smartphones holds great promise for enabling blind people to access printed information. Unfortunately, these systems suffer from a problem: in order for OCR output to be meaningful, a well-framed image of the document needs to be taken, something that is difficult to do without sight. This contribution presents an experimental investigation of how blind people position and orient a camera phone while acquiring document images. We developed experimental software to investigate if verbal guidance aids in the acquisition of OCR-readable images without sight. We report on our participant's feedback and performance before and after assistance from our software. PMID- 26677463 TI - Malposition of hemodialysis catheter in left superior intercostal vein. AB - Malposition of hemodialysis catheter needs to be identified promptly. Straight descent of left side internal jugular catheter mandates a thorough evaluation than unnecessary apprehensions. We report an unusual case of straight descent of hemodialysis catheter into superior intercostal vein. PMID- 26677462 TI - The effect of application of micromycetes on plant growth, as well as soybean and barley yields. AB - The possibility of application of micromycetes (strains Penicillium bilaiae Pb14, Aureobasidium pullulans YA05 and Rhodotorula mucilaginosa YR07) to increase yields of soybean (Glycine max cv Almaty) and barley (Hordeum vulgare cv Arna) was estimated. It was shown that the most positive effect on germination energy and seed germination after seed treatment with liquid culture, supernatant and filtrate, is achieved at 1:5 dilution. In studying the influence of cell associated and extracellular biologically active compounds of micromycetes (liquid culture and supernatant) on biometric parameters of seedlings, the maximum stimulating effect was observed in the variants with liquid culture. These strains of micromycetes were used as a bases for various compositions of preparations - application of each strain separately and application of micromycetes mixes. In microfield experiments, the increase of soybean yield ranged from 4.5 to 9.4 quintal/ha, barley - from 2.9 to 5.9 quintal/ha. A significant increase in various parameters of structure of the yield was shown in all experimental variants when compared to the control. It was found that an increase in soybean and barley yields and yield components was higher in the variant with a mix of micromycetes when compared to the separate application of each strain. The most efficient mixture was based on the mix of fungal strains (culture filtrate of P. bilaiae Pb14 diluted 1:5 + liquid cultures of A. pullulans YA05 and Rh. mucilaginosa YR07 in a 1:5 dilution). PMID- 26677464 TI - In Memoriam. Per Torsten Torstenson Kjellstrand, PhD (1941-2010). PMID- 26677465 TI - Preface. PMID- 26677466 TI - Marine biology: Charting sea life. PMID- 26677467 TI - Tobacco taxes. PMID- 26677468 TI - Financing future health. PMID- 26677469 TI - Mental health atlas. PMID- 26677470 TI - Lung function and metabolic syndrome: Findings of National Health and Nutrition Examination Survey 2007-2010. AB - BACKGROUND: Considerable uncertainty remains about obstructive lung function( OLF) in adults with metabolic syndrome (MetS). The aim of the present study was to examine pulmonary function status in adults with and without MetS. METHODS: We used data from 3109 participants aged >=20 years of the National Health and Nutrition Examination Survey 2007-2010. Subjects'MetS status was established on the basis of the 2009 harmonizing definition. Participants received spirometry. RESULTS: After age adjustment, 79.3% (SE 1.1) of participants with MetS had normal lung function, 8.7% (0.9) had restrictive lung function (RLF), 7.1% (0.8) had mild OLF, and 4.8% (0.6) had moderate OLF or worse. Among participants without MetS, these estimates were 78.7% (1.2), 3.9% (0.6), 10.9%(1.1), and 6.4% (0.8), respectively. After multiple adjustment, participants with MetS were more likely to have RLF (adjusted prevalence ratio [aPR] 2.20; 95% confidence interval [CI] 1.67, 2.90) and less likely to have any OLF (aPR 0.73; 95% CI 0.62, 0.86) than those without MetS. Furthermore, participants with MetS had lower mean levels of forced expiratory volume in one second (FEV1), FEV1 % predicted, forced vital capacity (FVC), and FVC % predicted, but a higher FEV1/FVC ratio than participants without MetS. Mean levels of FEV1, FEV1 % predicted, FVC, and FVC % predicted declined significantly, but not the FEV1/FVC ratio, as the number of components increased. CONCLUSIONS: Compared with adults without MetS, spirometry is more likely to show a restrictive pattern and less likely to show an obstructive pattern among adults with MetS. PMID- 26677471 TI - [Incidental finding of scrotal cystocele. Dumbbell sign]. AB - We present the case of a 60-year-old male diagnosed with end stage renal disease due to polycystic kidney disease (urinary flow rate between 100-150mL/24h) in the study to enter renal transplantation waiting list. The patient complained of a right inguinoscrotal bulky mass, first noticed several years before. Physical examination suggested an irreducible inguinoscrotal hernia and surgical repair was offered before transplantation. PMID- 26677472 TI - [Seminal vesicle abscess after acute prostatitis]. AB - A 45 year old male was referred to our clinic after an episode of acute prostatitis six weeks before, treated with ciprofloxacin for one month. Genital examination was normal with prostate slightly painful on DRE. PMID- 26677473 TI - [Not Available]. PMID- 26677474 TI - [Cutaneous metastasis of urothelial carcinoma of the bladder. A case]. PMID- 26677475 TI - [Spontaneous expulsion of large ureteral lithiasis]. PMID- 26677476 TI - A penis malformation in Etrusco-Roman art, condyloma, haemangioma or a sexual enhancement? PMID- 26677477 TI - [Retrocaval non-obstructive ureter and terminal megaureter. Case report]. PMID- 26677478 TI - [Images of kidney malformations in monozygotic twins]. PMID- 26677479 TI - EPs welcome new focus on reducing diagnostic errors. AB - Emergency medicine leaders welcome a major new report from the Institute of Medicine (IOM) calling on providers, policy makers, and government agencies to institute changes to reduce the incidence of diagnostic errors. The 369-page report, "Improving Diagnosis in Health Care," states that the rate of diagnostic errors in this country is unacceptably high and offers a long list of recommendations aimed at addressing the problem. These include large, systemic changes that involve improvements in multiple areas, including health information technology (HIT), professional education, teamwork, and payment reform. Further, of particular interest to emergency physicians are recommended changes to the liability system. The authors of the IOM report state that while most people will likely experience a significant diagnostic error in their lifetime, the importance of this problem is under-appreciated. According to conservative estimates, the report says 5% of adults who seek outpatient care each year experience a diagnostic error. The report also notes that research over many decades shows diagnostic errors contribute to roughly 10% of all.deaths. The report says more steps need to be taken to facilitate inter-professional and intra-professional teamwork throughout the diagnostic process. Experts concur with the report's finding that mechanisms need to be developed so that providers receive ongoing feedback on their diagnostic performance. PMID- 26677480 TI - Adequate number of clinicians on usability tests lacking, says study. AB - A new study reveals that some of the largest EMR vendors failed to meet certification standards, specifying that they state their user-centered design processes, and that they include at least 15 representative end-user participants in their usability tests. It is not clear why these vendors were certified despite not meeting the standards established by Office of the National Coordinator for Health Information Technology (ONC), but investigators suggest that emergency clinicians and administrators should engage with vendors early on, querying them about their user-centered processes. An analysis of the usability tests performed by 41 of some the largest EMR vendors found that 34% of them did not meet certification standards, specifying that they state their user-centered design process. Also, 63% of the vendors failed to include at least 15 representative end-users in their usability tests. Only 15% of the vendors used at least 15 participants who had clinical backgrounds in their usability tests. Experts urge clinicians to engage with EMR user groups to share best practices for optimizing specific EMR products. PMID- 26677481 TI - TJC: Time to curb patient falls in healthcare settings. AB - Noting that there are far too many falls in healthcare settings, The Joint Commission (TJC) has issued a Sentinel Event Alert, telling hospitals and other providers to take steps to identify patients at risk for a fall, and implement preventive interventions. However, while most falls occur in hospitals, preventing falls in the emergency setting presents some unique challenges. Since 2009, TJC says it has received 465 reports of patient falls with serious injury, and more than half of these have resulted in death. Most fall risk assessment tools are too cumbersome and take too long to complete at triage in the ED. The ED at Hartford Hospital in Hartford, CT, has implemented a streamlined risk assessment tool with just five "yes or no" factors for the triage nurse to consider. In concert with the risk assessment tool, the hospital has implemented a series of prevention interventions, including hourly rounding, bed alarms, post fall huddles, and a non-punitive culture for reporting falls. PMID- 26677482 TI - Distributors Offer New Beginning To Medication Management Therapy. PMID- 26677483 TI - Today's Medical Directors in Line To Be Tomorrow's Health Tech Chiefs. PMID- 26677484 TI - 'A Little Better All the Time (It Can't Get More Worse)'. PMID- 26677485 TI - Chief Experience Officers Push Patients to Forefront. PMID- 26677513 TI - Finally finished! National Competence Based Catalogues of Learning Objectives for Undergraduate Medical Education (NKLM) and Dental Education (NKLZ) ready for trial. PMID- 26677514 TI - More than just a NUMBER. PMID- 26677515 TI - Profession or job, does it matter? PMID- 26677516 TI - Considerations of the dual role. PMID- 26677517 TI - "They seem to be able to read your mind." An interview study to identify the cognitive non-technical skills of anaesthetic assistants. AB - The aim of this study was to identify the cognitive non-technical skills (i.e. situation awareness and decision making) used by anaesthetic assistants, as part of the development of a specialty-specific behavioural rating system for anaesthetic assistants. Semi-structured interviews were conducted with anaesthetic assistants (n=22), anaesthetic consultants (n=11) and trainee anaesthetists (n=12) in Scotland. The interviews were transcribed and thematically analysed. All 45 participants described the presence or failure of situation awareness (i.e. gathering information, its comprehension and anticipation) in 713 phrases. Decision making (i.e. considering options, selecting actions and reviewing decisions) by the anaesthetic assistants was reported much less frequently--only 34 participants described 89 phrases. Situation awareness is a key non-technical skill used by anaesthetic assistants, however decision making was less commonly described as required by anaesthetic assistants. This provides qualitative data to support the development of a non technical skills taxonomy for anaesthetic assistants. PMID- 26677518 TI - Exploring the perceptions of sterile services staff: a qualitative constructivist study. AB - With innovations in medicine and science, the extended roles for practitioners continue to evolve and merge, often crossing interprofessional boundaries. This paper presents a qualitative study which explored sterile services staff experiences of current practices and how they perceive the prospect of professionalisation. PMID- 26677519 TI - Are you prepared to take the risk: Extending governance for perioperative roles. AB - In the 25 years since the Oxford Heart Centre in England appointed the first British nurse to be formally trained as a non-medically qualified surgical assistant, the number of nurses and allied health professionals (AHPs) undertaking advancing surgical roles has increased in order to backfill the deficit of a surgical workforce (Quick and Hall 2014). Despite initial concerns over nurses and AHPs undertaking roles and responsibilities which were previously performed solely by doctors, the role of non-medical surgical assistants has been shown to maintain surgical services, provide an additional career route for nurses, and enhance patient care (Abraham 2011, Quick 2013, Jones et al 2012). In the early days however, a lack of role specific regulation, practice guidelines and a variety of educational standards led to variances in job titles and role responsibilities for nurses and AHPs performing surgical assistance (Box 1). PMID- 26677520 TI - Perioperative management of a placenta percreta: a case review. AB - This paper presents the management of a woman undergoing her fifth caesarean section in the presence of a placenta percreta. It reviews the incidence and surgical management of this complex pathology. Advanced planning and multidisciplinary coordination is crucial to successful treatment of this condition. There are implications for theatre staff of all professions to be confident and familiar with specialist equipment. Such cases represent a trend of multidisciplinary working that is increasingly part of current practice. PMID- 26677521 TI - PATTERNS OF NEURAL TUBE DEFECTS AT TWO TEACHING HOSPITALS IN ADDIS ABABA, ETHIOPIA A THREE YEARS RETROSPECTIVE STUDY. AB - BACKGROUND: Neural tube defects (NTDs), one of the most common congenital malformations, are potentially preventable cause of perinatal morbidity and mortality. OBJECTIVES: To give baseline description of NTDs and their outcome at two teaching hospitals in Addis Ababa, Ethiopia. MATERIALS AND METHODS: A retrospective cross sectional descriptive study conducted from September 2009 to August 2012. RESULTS: During the study period out of 28,961 deliveries 177 cases of NTDs were identified, giving an overall NTD prevalence of 6.1/1000. Only 12% (21/177) were diagnosed before 28 weeks of gestation. The mean gestational age at diagnosis of NTDs was 33.8 weeks (+/-5.5). Majority, 93.2% (165/177), had antenatal care (ANC) follow-up. Most, 72% (127/177), were diagnosed by ultrasound before delivery while 28% (50/177) were identified at the time of delivery or expulsion. Majority, 85.3% (151/177), never received folic acid supplementation. Only less than 1% (2/177) of the mothers started taking folic acid supplementation pre-conceptionally. Only a third, 33.3% (59/177), of the fetuses were born alive while only 13.6% (24/177) were discharged alive. Myelomeningocele, identified in 51.4% (91/177), was the commonest NTD in this study. CONCLUSION AND RECOMMENDATIONS: The proportion of NTDs in this study is among the highest globally reported rates. The practice of periconceptional folic acid supplementation is negligible. And although most had ANC follow-up the vast majority of NTDs were diagnosed late in the third trimester. It is, therefore, highly recommended to consider implementing national preventive strategies to reduce the prevalence of NTDs in Ethiopia. PMID- 26677523 TI - TRENDS IN CARDIOVASCULAR DISEASE OVER TIME: A 30-YEAR RETROSPECTIVE ANALYSIS OF MEDICAL-ICU ADMISSIONS IN ADDIS ABABA, ETHIOPIA. AB - BACKGROUND: Increased urbanization with change in lifestyle in many developing countries exposed them to the challenge of double disease burden, battling with the existing communicable infectious diseases as well as the emerging epidemic of NCDs. OBJECTIVE: To describe trends of medical intensive care unit admission over thirty years in Ethiopia. METHODS: MICU registries at Tikur Anbessa Specialized Hospital over a thirty year period were examined for discharge diagnosis. Data included for analysis were selected at ten-year interval of equivalent six- months' period from December to May of 1981/82, 1991/92, 2001/02 and 2011/12. Variables included were age, gender, residence, discharge diagnosis, duration of stay in hospital, discharge status, admission date, and admission source. Obtained data were cleaned, coded, recoded and edited. The analysis was done using SPSS 15.0 statistical soft ware. RESULTS: A total of 500 cases are included for analysis. Among these 284 (57%) were male. The mean age was 40.2 +/- 18 years rangingfrom 13 to 87 years. The aggregate cardiovascular disease, other non communicable disease and infectious disease as a cause of admission in the past thirty years were 213 (42.6), 141 (22.8), 105 (20.0) respectively. Unlike the other disease category cardiovascular disease increased steeply over the past thirty years. Overall case fatality rate at MICU was 31.6% ranging from 24.8% of other-NCD to 46.7% of infectious diseases. CONCLUSION: Cardiovascular disease has steeply increased till it became predominant in the last decade at MICU of TASH. PMID- 26677522 TI - MAJOR RISK FACTORS, CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA; A RETROSPECTIVE STUDY AT TIKUR ANBASSA HOSPITAL, ADDIS ABABA UNIVERSITY, ADDIS ABABA, ETHIOPIA. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide accounting for over half a million deaths per year. Hepatocellular carcinoma can occur secondary to viral hepatitis, HBV or HCV. It can also occur secondary to other causes of Cirrhosis (alcoholism being the other most common cause). OBJECTIVES: To describe clinical and laboratory characteristics of Hepatocellular carcinoma in a tertiary care hospital in Addis Ababa, Ethiopia. METHODS: A retrospective study was conducted in patients admitted to Tikur Anbassa specialized Hospital with a diagnosis of Hepatocellular carcinoma during the period of January 1, 2013 to Dec. 31, 2015. Data were collected using structured questionnaire on basic demographic factors, behavioral risks, laboratory profiles and imaging reports. Descriptive analysis was performed on the data collected. RESULTS: Fifty one patients fulfilled the criteria for Hepatocellular carcinoma in the study period. Thirty nine were males and 12 were females. Hepatitis B and C viruses were found to be the causes for HCC in 48% of the cases. History of alcohol abuse was documented in 45% % of the individuals. About 26% of the patients had Ascites, 35% were found to have portal vein thrombosis, The child-Pugh score for patients who had complete profile were Child A 46%, Child B an equal percentage of 46% andfor Child C 0.7%. CONCLUSION: The contribution of Hepatitis virus is high with equivalent proportion of HBV and HCV. Alcohol intake and unidentified risk factors have also played for another half of the causes. Almost a third of patients have Portal vein thrombosis and 96% were either Child Pugh A or B. Enhancing immunization coverage frequent use of infection prevention and availability of treatment for viral hepatitis will help to reduce Hepatocellular carcinoma. PMID- 26677524 TI - PATTERNS AND DETERMINANTS OF PRE-HOSPITAL CARE AMONG TRAUMA PATIENTS TREATED IN TIKUR ANBESSA SPECIALIZED HOSPITAL, EMERGENCY DEPARTMENT. AB - BACKGROUND: Injury remains the major cause of death and disability worldwide, and places an enormous burden on countries with limited resources in which Ethiopia is included. OBJECTIVE: It is obvious that pre-hospital care is a essential part of the treatment process in many acute disease and trauma. METHODS: Cross sectional study design using structured interviewing questionnaire which was conducted in 437 Trauma patients who came to emergency department of Tikur Anbesa Specialized Hospital from February 1 to March 30, 2013. RESULTS: Only 73 (16.7%) patients got some kind of basic cars like stop bleeding, positioning, immobilization by ambulance staff 41 (51.2%), relatives 24 (30%) and police and bystanders 14 (20.3%). Commonest means of transportation in which 59% of cases arrived by taxi while about 14.4% were brought in by ambulance. Most patients arrived to definitive care from the scene after are (the golden) hour of injury, has passed; only 81 (18.5%) of patients arrived in less than and within one hour. CONCLUSION: Proportion of patients, who received care before they arrived in the hospital was very small. Time of arrival to definitive care was prolonged and use of ambulances for transportation was minimal. PMID- 26677525 TI - MANAGEMENT OF PHEOCHROMOCYTOMA IN THE ABSENCE OF ALPHA BLOKERS: A CASE REPORT FROM AYDER REFERRAL HOSPITAL. AB - A 13-year-old girl with right adrenal pheochromocytoma pretreated with Nifedipine, underwent surgical removal of the tumor. General anesthesia with Propofol infusion and pethidine analgesia was performed. To control the blood pressure (BP), Nitroglycerine infusions were administered successfully. Following the ligation of the adrenal veins, patient was hypotensive and inotropic support was required. This case report showed that in the absence of alpha blockers and short acting drugs the surgery could be done with a very good follow up and Nitroglycerine as antihypertensive. PMID- 26677526 TI - FATAL TRACHEO-INNOMINATE ARTERY FISTULA ASSOCIATED WITH A TRACHEOSTOMY TUBE AT A TEACHING UNIVERSITY HOSPITAL IN ADDIS ABABA: CASE REPORT AND REVIEW OF LITERATURE. AB - Tracheo-innominate artery fistula (TIAF) is a potentially lethal but rare complication associated with tracheostomy. As tracheostomies are one of the common life saving procedures that are performed routinely in the country, bring this complication to the attention of all health care professionals is of paramount importance. Hence, this case report is prepared. PMID- 26677527 TI - FIBULAR HEMIMELIA: A RARE CASE REPORT. AB - Fibular hemimelia is a rare congenital absence of the fibula that may occur as an isolated anomaly or as a part of a malformation syndrome. Shortening of the extremity is obvious at birth with leg-length discrepancy. On plain radiograph of the leg and foot, significant deficiency or absence of the fibula can be seen. In this case report, a 6 year old boy with fibular hemimelia is presented. Radiological diagnosis and differential diagnosis are discussed. PMID- 26677528 TI - Looking forward. PMID- 26677529 TI - #ILookLikeASurgeon goes viral: How it happened. PMID- 26677530 TI - Social media: Threat to professionalism and privacy or essential for current surgical practice? PMID- 26677531 TI - First-place essay--Pro. Social media: An essential tool for the academic surgeon. PMID- 26677532 TI - First-place essay--Con: The writing is on the (Facebook) wall: The threat posed by social media. PMID- 26677533 TI - Surgeons help with recovery after earthquake in Nepal. PMID- 26677534 TI - The College weighs in on leading health care issues. PMID- 26677535 TI - State lobby days provide opportunity to influence legislative action. PMID- 26677536 TI - Medicare and Medicaid audits. PMID- 26677537 TI - Response to preoperative endocrine therapy in breast cancer patients can alter surgical and chemotherapy options. PMID- 26677538 TI - Dr. and Mrs. Kenyon are committed to giving back. PMID- 26677539 TI - RPI can be used to improve surgical care. PMID- 26677540 TI - NTDB DATA POINTS: Black Wednesday. PMID- 26677541 TI - RE-IMAGINING IMAGING. Providers looking to analytics tools to cope with value based care. PMID- 26677542 TI - TECH'S ROLE IN POP HEALTH. Obscure patient info helps providers individualize care. PMID- 26677543 TI - Accountable Care Drives URGENT CARE. IT plays a key role in coordinating healthcare. PMID- 26677544 TI - CHALLENGES AHEAD FOR PORTALS. Patients are using them more, but APIs may be better for engagement. PMID- 26677545 TI - Data for Value. PMID- 26677546 TI - [How to interpret a semen sample?]. AB - Semen sample belongs to the basic examinations for couples suffering from infertility. To ascertain reliable results, the patients must be provided with adequately detailed instructions regarding the sample collection. The interpretation should not aim at a too precise appraisal about fertility. On the other hand, causes for the semen's clearly impaired ability to fertilize must be solved without delay. Good anamnesis will help to interpret the semen analysis and accelerate and direct further exploration. The semen sample should always be repeated, if the answer clearly deviates from normal. PMID- 26677547 TI - [Tobacco, snuff and oral health]. AB - Smoking is estimated to cause 6.3 million deaths annually worldwide. The use of snuff, differing from smoking, has significantly increased especially among the adolescents. Snuff powder contains 20-fold more nicotine compared to cigarettes, leading to strong nicotine addiction. In addition to cancer development, both smoking and snuff use exert other risks for oral health. Compared with non smokers, smokers are at a 10-fold risk for the development and progression of periodontal diseases. Snuff causes oral mucosal changes, gingival recessions and root surface caries. Smoking induces systemic low-grade inflammation, which weakens defensive immune responses in oral mucosa, gingiva, gingival crevicular fluid and saliva. PMID- 26677548 TI - [Clinical pathology on the verge of virtual microscopy]. AB - For more than 100 years, examinations of pathology specimens have relied on the use of the light microscope. The technological progress of the last few years is enabling the digitizing of histologic specimen slides and application of the virtual microscope in diagnostics. Virtual microscopy will facilitate consultation possibilities, and digital image analysis serves to enhance the level of diagnostics. Organizing and monitoring clinicopathological meetings will become easier. Digital archive of histologic specimens and the virtual microscopy network are expected to benefit training and research as well, particularly what applies to the Finnish biobank network which is currently being established. PMID- 26677549 TI - [Problems in the development of emotional expression--dictated by temperament or environment?]. AB - Learning of emotional regulation skills is based on parent-child interaction. The difficulty in recognition and expression of emotions, along with outsourced thinking and weak imagination are collectively termed alexithymia, the inability to express emotions. Temperament has been shown to account for 20 to 40% in the development of alexithymia. Alexithymia has been found to be associated with introversion, negative emotionality and avoidance of problems, and an insecure affectional tie. Attachment theory is based on early interaction, the establishment of which in turn reflects the temperament features of the child and the parent, and differences in these features. PMID- 26677550 TI - [Evolutionary history of human locomotor system--from walking to long-distance running]. AB - Bipedality evolved in hominids more than 4 million years ago. Bipedals were a diverse group including the lineage of obligatory walkers that finally lead to humans. Important anatomical changes in this group were: enhanced lumbar lordosis, shortening of the ilium, and emphasize on the parasagittal movements. Long-distance running evolved much later and it was associated with well developed plantar arches, strengthening of muscles supporting the erect trunk, and decoupling of the pectoral girdle and head. In addition to anatomical changes, humans have many physiological adaptations to long-distance running. It is likely that the ability to run long-distance has been important for the survival of our species. PMID- 26677551 TI - [Health information and social media: the doctor as a primary school teacher again]. AB - While health information reaches an increasing proportion of the population through social media, there is no guarantee that the provided information is always either up-to-date or correct. Besides possessing know-how on the assessment of the quality of provided information, doctors are also obliged to offer health information wherever it is requested. It is important for doctors to be present in social media to evaluate and provide health information. This is associated with interesting ethical and judicial questions. PMID- 26677552 TI - [Flipped classroom in basic medical education]. AB - Medical education is facing changes in order to improve young doctors' competency to respond better to current needs of the patients and the society. Both curriculum content and teaching methods are revised. In addition to vibrant research in academic medical education, teachers are supported by the improved web-based learning environments and novel technical tools. Flipped classroom, a new paradigm that benefits from technical development, provides many opportunities for medical education. This teaching method always consists of two mutually complementary parts. The first part of the learning action takes place independently off classroom with video lectures or other stimuli for learning. The second part takes place in conjunction with the teacher and other students, and requires student group interactions. PMID- 26677553 TI - [Medical intern or locum doctor--does job position affect learning?]. AB - At the University of Helsinki, the licentiate degree in medicine involves internships that can be conducted as a medical intern or locum doctor. The students and their supervisors fill out a feedback form, which helps in assessing the students' improvement in various areas. Based on the feedback form between 2008 and 2013, students having worked as locum doctor rated better improvement in their diagnostic skills, writing medical records, interacting with the patient, and operating in the work community. Supervisor evaluations did not show a similar clear difference between the job positions. PMID- 26677554 TI - Becoming a Nimble Leader. Leading teams through change requires agility and masterful execution. PMID- 26677556 TI - WHEN TWO CULTURES MERGE: CREATING A NEW AND IMPROVED HEALTHCARE ORGANIZATION. PMID- 26677555 TI - Leading Change From the C-Suite: 3 Leaders Share Their Strategies. PMID- 26677557 TI - CASE STUDIES IN PRICE TRANSPARENCY. Leading hospitals and health systems recognize that enhancing their patient financial communications can boost consumer satisfaction, loyalty and even the bottom line. PMID- 26677558 TI - The Ethics of Big Data. There's a fine line between patient privacy and identifying better forms of treatment. PMID- 26677559 TI - Why Culture Change Is Critical to Lean Initiatives. Lean training and coaching alone are not enough to improve customer satisfaction. PMID- 26677560 TI - Transforming Diabetes Care Using Telehealth. Patients in rural areas benefit from remote monitoring. PMID- 26677561 TI - Insurance Exchanges Here to Stay. The next evolution of healthcare likely will include an advanced form of exchanges. PMID- 26677562 TI - Breaking the Glass Ceiling in Healthcare. Leaders can support gender equality in the executive suite in several ways. PMID- 26677563 TI - Embracing Digital Transparency. Access to provider information online increasingly influences consumer choice. PMID- 26677564 TI - 10 New Rules to Accelerate Healthcare Redesign. Bold aspirations to guide healthcare organizations during an era of reform. PMID- 26677565 TI - Transitioning to a Physican-Driven Health System. UnityPoint takes a different approach to engagement. PMID- 26677566 TI - [100th Anniversary of Professor David Shugar]. PMID- 26677567 TI - [Map of Polish Biochemistry]. PMID- 26677568 TI - [Map of Polish Biochemistry]. PMID- 26677569 TI - [Short history of conference "Inhibitors of Protein Kinases"]. PMID- 26677570 TI - [Photochemistry and UV Spectroscopy of Proteins and Nucleic Acids]. AB - The article presents a short history of David Shugar studies in the field of photochemistry and UV spectroscopy of proteins and nucleic acids, carried out since the late 1940s. to the beginning of the 1970s. of the 20th century, with some references to the state of related research in those days. PMID- 26677571 TI - [Cytochemical localization and properties of selected nucleolytic enzymes]. AB - In the article there are shortly outlined studies on cytochemical localization of selected nucleolytic enzymes carried out between 1957-1986 by David Shugar and his coworkers. The histochemical localization of several nucleolytic enzymes in animal and plant tissues was determined by synthesis of specific substrates, alpha-naphthyl esters of 5'- and 3'-nucleotides and their derivatives. In rat tissues phosphodiesterase I was localized in the plasma membrane whereas phosphodiesterase II in the lizosomes, reflecting their physiological roles. The localization of pancreatic type ribonuclease in animal tissues was determined, indicating its role in extracellular digestion. Plant nucleotide pyrophosphatase was localized in several tissues, purified to near homogeneity from potato tubers and its properties and substrate specificity were determined. Application of this enzyme for removal of m7GMP from the "cap" of eukaryotic mRNA allowed to elucidate the role of "cap" in mRNA binding to ribosomes in the process of translation. Furthermore, cyclic nucleotide phosphodiesterase was isolated from potato tubers and its physicochemical properties, oligomeric structure and substrate specificity were elucidated. PMID- 26677572 TI - [Genetic transformation and fate of heterological DNA in bacterial cells]. AB - Secretion of a metabolite enabling Streptococci to undergo genetic transformation was discovered. The metabolite combined with an optimization process were applied to increase the transformation yield about 20-fold. It was observed that large amounts of DNA exert a bactericidal effect, indicating the ability of at least 70% of cells to uptake the polymer. While studying the molecular mechanism of transformation of Bacillus subtilis it was shown that the uptaken DNA forms complexes with bacterial proteins, which hinders determination of its structure. A method was found to dissociate these complexes which enabled to determine the single-stranded structure of the uptaken DNA. Donor DNA fragments incorporated into the host DNA were of about 10 Da. Non-transforming DNA can be uptaken similarly but does not undergo incorporation into the host DNA. The selectivity of Bacillus subtilis receptors was determined towards DNA of phages containing modified bases: uracil, putrescinyl-thymine and its acetylated derivative, 5' hydroxymethylcytosine and its glycosylated derivative and also towards double stranded RNA of f2 phage. All these modifications were tolerated by the cellular receptors, with the exception of glycosylation and the 2'-OH group in RNA. PMID- 26677573 TI - [Purine and pyrimidine nucleoside phosphorylases - remarkable enzymes still not fully understood]. AB - Purine and pyrimidine nucleoside phosphorylases catalyze the reversible phosphorolytic cleavage of the glycosidic bond of purine and pyrimidine nucleosides, and are key enzymes of the nucleoside salvage pathway. This metabolic route is the less costly alternative to the de novo synthesis of nucleosides and nucleotides, supplying cells with these important building blocks. Interest in nucleoside phosphorylases is not only due to their important role in metabolism of nucleosides and nucleotides, but also due to the potential medical use of the enzymes (all phosphorylases in activating prodrugs - nucleoside and nucleic base analogs, high-molecular mass purine nucleoside phosphorylases in gene therapy of some solid tumors) and their inhibitors (as selective immunosuppressive, anticancer and antiparasitic agents, and preventing inactivation of other nucleoside drugs). Phosphorylases are also convenient tools for efficient enzymatic synthesis of otherwise inaccessible nucleoside analogues. In this paper the contribution of Professor David Shugar and some of his colleagues and coworkers in studies of these remarkable enzymes carried out over nearly 40 years is discussed on the background of global research in this field. PMID- 26677574 TI - [Thymidylate synthase-catalyzed reaction mechanism]. AB - Thymidylate synthase ThyA (EC 2.1.1.45;-encoded by the Tyms gene), having been for 60 years a molecular target in chemotherapy, catalyses the dUMP pyrimidine ring C(5) methylation reaction, encompassing a transfer of one-carbon group (the methylene one, thus at the formaldehyde oxidation level) from 6R-N5,10 methylenetetrahydrofolate, coupled with a reduction of this group to the methyl one, with concomitant generation of 7,8-dihydrofolate and thymidylate. New facts are presented, concerning (i) molecular mechanism of the catalyzed reaction, including the substrate selectivity mechanism, (ii) mechanism of inhibition by a particular inhibitor, N4-hydroxy-dCMP, (iii) structural properties of the enzyme, (iv) cellular localization, (v) potential posttranslational modifications of the enzyme protein and their influence on the catalytic properties and (vi) non catalytic activities of the enzyme. PMID- 26677575 TI - [Synthesis, conformation, and spectroscopy of nucleoside analogues concerning their antiviral activity]. AB - Chemically modified analogues of nucleosides and nucleotides, have been thoroughly investigated since the discovery of DNA double helix by Watson and Crick in 1953 (Nature 171: 737). Chemical structures, first of all tautomerism, of the nucleic acid bases, as well as the conformations of the nucleic acids constituents, determine the secondary and tertiary structures of DNA and RNA polymers. Similarly, structural and dynamic parameters of nucleoside derivatives determine their biological activity in mutagenesis, neoplastic transformation, as well as antiviral or anticancer properties. In this review, a multidisciplinary approach of Prof. David Shugar's group is presented in the studies on nucleosides and nucleotides. It consists in chemical syntheses of suitable analogues, measurements of physicochemical and spectral parameters, conformational analysis by means of nuclear magnetic resonance (NMR) and X-ray diffraction, as well as characteristics of the nucleoside analogues as inhibitors of some selected, target enzymes, crucial in respect to antiviral activity of the analogues. These long-lasting studies follows upon the line of the main paradigm of molecular biophysics, i. e. structure-activity relationship. PMID- 26677577 TI - [Role of tautomerism in the molecular mechanisms of mutagenesis]. AB - Environment of human being usually contains a high number of environmental mutagens, which may modify chemically nucleic acid bases into promutagenic analogues. Hydroxylamine (NH2OH) is a strong mutagen which modifies cytosine and adenine to N4-hydroxycytosine and N6-hydroxyadenine, respectively. Once these analogues are present in DNA or RNA, they may cause transition point mutations by the exchange between two pairs C:G and A:T into T:A and G:C, respectively. The reason for these mutations is the change of preferences between intermolecular hydrogen bonds resulting from the shift of the tautomeric equilibrium from the preferred amino form into the imino one. In the case of the amino<-->imino tautomeric equilibrium of N6-hydroxyadenosine, it was also shown that preferential hydrogen bonding between its imino form and cytidine, or uridine and the amino form of this base leads to the shift of the tautomeric equilibrium in favour of these tautomers in solution. N4-hydroxy-dCMP analogues exhibited very interesting inhibitory properties versus the biosynthesis of dTMP catalyzed by thymidylate synthase. These properties help to further the knowledge on the molecular mechanism of the catalytic reaction of this enzyme as well as on the role of syn-anti photoisomerization of the N4-hydroxy group in this reaction. Examinations gathered in the article were conducted from 1979 to 1985 under supervision, and afterwards from 1986 to 2004 in collaboration with professor David Shugar. PMID- 26677576 TI - [The specific enzyme inhibitors for potential therapeutic use]. AB - Therapy for hepatitis C virus (HCV) initially consisted on administering ribavirin - having a broad spectrum of action - and pegylated interferon, and was only effective in 40-50% of patients. Appropriate was to find effective inhibitors of viral replication e.g. by inhibition of a viral enzyme, NTPase/helicase required in the process of translation and RNA replication of the HCV. We developed methods of synthesis of many compounds belonging to different groups - derivatives of nucleosides, benzotriazole, benzimidazole, tropolone and epirubicine. Some of the derivatives inhibit HCV helicase activity at low concentrations and reduces replication of the viral RNA in subgenomic replicon system. In the process of HCV replication casein kinase CK2 plays an important role. It regulates the level of phosphorylation of HCV protein NS5A, which affects the production of infectious virions of HCV. Effective and selective inhibitors of kinase CK2 could be of use in the treatment of HCV in combination with other drugs. CK2 kinase phosphorylates approximately 300 proteins that affect the growth, differentiation, proliferation or apoptosis. Elevated CK2 kinase activity has been observed in several types of cancer and other diseases, therefore, inhibitors of this enzyme are potential therapeutic importance, particularly for anti-cancer treatment. Research carried out in collaboration with prof. Shugar led to the synthesis of one of the most selective inhibitors of this enzyme which is 4,5,6,7-tetrabromo-1H-benzotriazole, used for the study of the role of kinase CK2 in a number of metabolic processes in tumor cells. PMID- 26677578 TI - [Tautomerism of purine and pyrimidyne bases]. AB - In this paper, I am presenting the background and a short outline of the research on the neutral and ionic tautomeric forms of pyrimidines, purines and their derivatives, carried out in the late 1960s under the guidance of professor David Shugar, in the Biophysics Department of Warsaw University. PMID- 26677579 TI - [Contribution of a halogen bond to binding of halogenated ligands by protein kinases]. AB - This article presents a brief overview of recent studies on the phenomena of halogen bonding, most of which have been done for the last 15 years in the collaboration with Prof. David Shugar. All these investigations concern reliable estimation of the thermodynamic contribution of a halogen bond to protein-ligand interactions. PMID- 26677580 TI - Inhibin A and B levels in serum and follicular fluids of women with various reproductive failures undergoing in vitro fertilization. AB - OBJECTIVE: Ovarian inhibins (INH) are hormones participating in the regulation of gametogenesis. We monitored inhibin A and B levels in serum (S) and follicular fluids (FF), depending on the type of fertility failure and treatment outcome. MATERIAL AND METHODS: We examined INHA and B levels in S and FF of 72 women undergoing ovarian stimulation for in vitro fertilization, including embryo transfer We took serum samples at the time of egg collection (S1), embryo transfer (S2), and diagnostics of early pregnancy (S3). FF samples were obtained during egg collection. INH A and B levels were measured by ELISA set kit in all media. RESULTS: Healthy women had median of INHA S1 592.02pg/ml INHA S2 593.58pg/ml, INHA S3 15.17pg/ml and INH B S1 242.46pg/ml, INH B S2 and INH B S3 zero levels. Women with ovarian disorders had significantly lower levels of INH A S1 and INH A S2 (p<0.05). Women with polycystic ovaries had significant higher INH B S2 levels (p<0. 05). No statistically significant differences were found in women with endometriosis. Presence of oocyte in the dominant follicle positively correlated with INH B FF levels (p<0.05). CONCLUSIONS: WE confirmed differences in the levels of inhibins in sera depending on type of fertility failure. Inhibin B better reflected the presence of an oocyte. The potential paracrine role of inhibins needs to be examined to improve preparation for the in vitro fertilization treatment (IVF). PMID- 26677581 TI - Cesarean myomectomy and possible risk factors for admission to intensive care unit - a retrospective study. AB - OBJECTIVES: Cesarean myomectomy (CM) allows to remove fibroids and to restore uterine anatomy during delivery combining two operations in one. It was opposed in the past due to surgical risks, although many reports showed that CM was not associated with increased morbidity The risk for admission to an intensive care unit (ICU) following CM - as an objective indicator of maternal morbidity potentially resulting in greater morbidity for patients, increased length of hospital stay and higher hospital costs - has been poorly evaluated in the literature. The aim of our investigation is to estimate risk factors for ICU admission after CM. MATERIAL AND METHODS: The patients were subdivided into two groups: 57 women who were postoperatively admitted to the ICU (study group), and 45 women not treated in the ICU (control group). The p-value of <0.05 was considered as statistically significant. RESULTS: Data showed no statistically significant differences with regard to demographic factors, comorbidity and indications for cesarean section, as well as experience of the surgeon, number of hysterotomies, and incidence of emergency CS between the two groups. The most common reason for admission to the ICU was intraoperative hemorrhage (61.40%). As for the surgical characteristics, the study group showed significant increase in the rates of intraoperative transfusion (p=0.000) and intraoperative hemorrhage (p=0.000), as well as prolongation of surgical time (p=0.002). Myoma type and size were also significantly different between the groups (p=0.003 and p=0.000, respectively). CONCLUSIONS: The most important factor contributing to ICU admission after CM is intraoperative hemorrhage in case of bigger myomas and prolonged surgeries. PMID- 26677582 TI - [Evaluation of tissue metaloproteinases inhibitors TIMP-2 and TIMP-4 in III-rd trimester of pregnancy]. AB - INTRODUCTION: To achieve physiological pregnancy development proper implantation and placental development is needed to establish good exchange between mother and fetus. Metaloproteinases of extracellular matrix are responsible of its degradation, their action is decreased by metaloproteinases inhibitors - TIMPs. OBJECTIVES: Assessment of the concentrations soluble extracellular matrix metaloproteinases inhibitors TIMP-2 and TIMP-4 in blood of pregnant healthy women in III-rd trimester and in umbilical cord blood separately from arteries and umbilical cord vein. MATERIAL AND METHOD: The study was conduced in High Risk Pregnancy Clinic, Medical University Lodz. The study group consisted from 29 women in normal, eutrophic pregnancy between 37 and 40 weeks of pregnancy TIMP-2 and TIMP-4 were measured in blood samples from maternal blood and umbilical cord vessels - separately from arteries and vein. RESULTS: Mean TIMP-2 concentration in maternal blood was 101,27 ng/ml, from umbilical artery 108,88 ng/ml, and from vein 108,28 ng/ml. Mean concentration of TIMP-4 in maternal blood was 726,73 pg/ml in umbilical artery was 529,95 pg/ml, in umbilical vein - 537,87 pg/ml. Comparing obtained results of TIMP-4 statistical difference between maternal blood and umbilical cord blood was found. CONCLUSIONS: The lack of increase of TIMP-2 synthesis in III-rd trimester of physiological pregnancy may be result of stabile vascularisation process. Observed decrease of TIMP-4 concentration may be the result of normal blood vessels development and the lack of increase angiogenesis process in both mother and fetus. PMID- 26677583 TI - Coexistence of the 677C>T and 1298A>C MTHFR polymorphisms and its significance in the population of Polish women. AB - OBJECTIVES: The aim of the study was to evaluate the frequency of the 677C>T and 1298A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population. MATERIAL AND METHODS: A total of 662 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 677C>T and 1298A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods. RESULTS: The frequency of the 677CC, 677CT and 677TT genotypes in the studied population of women was 50.60%, 39.88% and 9.52%, respectively As to the 1298AA, 1298AC and 1298CC genotypes, the obtained results were as follows: 42.75%, 47.88% and 9.37%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 677CC/1298AC (28.85%), 677CT/1298AA (20.85%) and 677CT/1298AC (19.03%) genotypes. The coexistence of 677CC/1298AA (12.39%), 677CC/1298CC (9.37%) and 677TT/1298AA (9.51%) genotypes was observed less frequently In the studied population of Polish women, the coexistence of 677CT/1298CC, 677TT/1298AC and 677TT/1298CC genotypes has been not observed. CONCLUSIONS: The frequency and coexistence of genotypes of the 677C>T and 1298A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other North-European populations. Women carriers of the mutated variants of both, 677C>T and 1298A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosis-related complications during pregnancy It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age. PMID- 26677584 TI - Reproductive outcomes of intracytoplasmic sperm injection (ICSI) in good prognosis patients who electively decided to limit the number of oocytes used for microinjection: a two-center comparative study. AB - OBJECTIVES: The aim of the study was to compare the outcomes of intracytoplasmic sperm injection/embryo transfer (ICSI/ET) between two IVF centers with similar pregnancy rates and embryo transfer policy but with two different approaches to good-prognosis patients who intentionally chose to limit the number of oocytes used for ICSI. MATERIAL AND METHODS: It was a retrospective two-center comparative study A total of 218 patients after successful retrieval of >10 mature oocytes following ovarian hyperstimulation were included in the study The number of fertilized oocytes used during ICSI/ET was limited to 6 and 10 in 108 and 110 patients of the Centre for Reproductive Medicine KRIOBANK and VitroLive Fertility Clinic, respectively RESULTS: No significant differences in the implantation rate (29.93% vs. 29.54%; p=0.94) and ongoing pregnancy rate (39.81% vs. 45.45%, p=0.40) were observed between patients who electively fertilized 6 as compared to 10 oocytes, respectively However in patients who deliberately limited the number of fertilized oocytes to 6 the following were observed: i) significantly fewer embryos available for ET (2.89 +/- 1.23 vs. 3.77 +/- 1.48, p<0.0 1); ii) considerably lower number of frozen embryos per cycle (1.05 +/- 1.30 vs. 2.00 +/- 1.67, p<0.01), and iii) lower rates of cycles with embryo cryopreservation (4 7.22% vs. 72.72%, p<0.01) as compared to patients with 10 fertilized oocytes. CONCLUSIONS: Elective fertilization of 6 vs. 10 oocytes does not adversely affect fresh ICSI/ET outcome in normal-responding patients. Restricted number of oocytes used for ICSI/ET may be a favorable alternative for couples who do not wish to cryopreserve surplus human embryos. PMID- 26677585 TI - Concurrent endometrial carcinoma in hysterectomy specimens in patients with histopathological diagnosis of endometrial hyperplasia in curettage specimens. AB - OBJECTIVES: The purpose of this study was to appraise the presence of Endometrial Carcinoma (EC) sequence in patients undergoing hysterectomy for Endometrial Hyperplasia (EH). MATERIAL AND METHODS: Eighty-two patients undergoing hysterectomy with the indication of EH based on endometrial curettage between January 2009 and December 2013 were analyzed respectively All patients with a diagnosis of EH were investigated for age, parity history of diabetes mellitus and hypertension. The histopathology of the hysterectomy specimens were compared with their curettage specimens. RESULTS: A total number of 82 women; 48 (58.5%) postmenopausal and 34 (41.5%) premenopausal were determined to have EH on histopathological evaluation of endometrial tissues obtained by endometrial curettage performed for evaluation of various bleeding abnormalities. Mean-age of patients was 54.6?8.7. Among 82 patients found to have EH on curettage specimens 39 had EC on hysterectomy specimens (39/82. 47.5%). Consequently we determined well differentiated endometrial adenocarcinoma in 66% (35/53) of the patients with hyperplasia with atypia (17/35. 48.5% Grade 1 and 18/35.51.4% Grade 2) and 13.7% (4/29) hyperplasia without atypia (4/4.100% Grade 1). CONCLUSIONS: Postoperative diagnosis of endometrial pathology might be different from that of preoperative especially in cases with complex EH with atypia. Our study indicated that most of women diagnosed preoperatively with Atypical endometrial hyperplasia (AEH) may have a cancer at final examination of hysterectomy specimens. It may be useful to operate patients with AEH in specific centers because of invasive endometrial cancer risk in final histopathological evaluation. PMID- 26677586 TI - [Fertility-sparing surgical management of ovarian cancer]. AB - INTRODUCTION: Ovarian cancer (OC) continues to be one of the greatest challenges of modern oncology gynecology Most patients are diagnosed in the advanced stage of the disease, which requires aggressive and extensive surgical intervention. In approximately 8% of the cases, OC affects women <40 years of age. Among them, early-stage OC FIGO IA accounts for 40% of the affected individuals, which allows for fertility-sparing surgical management. OBJECTIVES: The aim of the study was to evaluate the efficacy of fertility-sparing management in OC women, with tumor limited to one ovary who wish to preserve their fertility MATERIAL AND METHODS: A total of 43 women with OC limited to one ovary (26 with borderline malignant tumors and 17 with invasive tumor FIGO IA) underwent surgical sparing therapy Disease recurrence rate as the measure of the quality of treatment and the number of pregnancies, together with their course, as the measure of the effectiveness of the fertility-sparing therapy were evaluated. RESULTS: The observation period, from 4-10 years for borderline malignancy and 3-8 years for invasive FIGO IA tumor revealed no cases of disease recurrence. In the former group, 14 (73 %) women conceived, out of whom 2 miscarried before 22 weeks of gestation, 1 give birth pre-term, i.e. at 34 weeks of gestation, 10 (71.5%) gave birth at term, and 1 is pregnant (6 months) at the time of the publication of the study In the later group, 9 (81.8%) women conceived, out of whom 1 miscarried at 10 weeks of gestation, 1 had a case of intrauterine fetal demise at 27 weeks of gestation, 6 gave birth at term, and 1 is pregnant (3 months) at the time of the publication of the study CONCLUSIONS: Proper patients selection for fertility-sparing management, as well as the way of performing the surgery allow for adequate control of the malignant process in patients with tumor limited to one ovary and preservation of fertility PMID- 26677587 TI - [Correlation between intensity of menopausal symptoms and cognitive domain assessed with CNS-VS tests]. AB - INTRODUCTION: Numerous publications suggest that many cognitive domains deteriorate with age. As far as postmenopausal women are concerned, the question remains whether the process is caused only by an ageing brain or also by the menopause. The objective of this research was to analyze a possible correlation between intensity and duration of menopausal symptoms and the level of cognitive domains measured with CNS-VS tests among post-menopausal women. METHODOLOGY: The group under examination included 383 postmenopausal women (at least 2 years after their last menstruation) from South-Eastern Poland. The following inclusion criteria were used: age 50-65, good overall health status, at least primary level of education, and FSH>30 mlU/ml. Cognitive domains were assessed using the CNS - VitalSigns diagnostic device. The intensity of menopausal symptoms was measured with the Kupperman Index and the Greene Scale. The statistical analysis was conducted with the use of the Statistica software. RESULTS: There were no significant relations between age at last menstruation and cognitive domains. BMI was oositively correlated with the Neurocognitive index (NCI) and memory visual memory processing speed, and executive functions. The intensity of menopausal symptoms measured with the Greene Scale was negatively correlated with NCI and most of the cognitive domains, whereas symptoms measured with the Kupperman Index were negatively correlated with NCI and visual memory CONCLUSIONS: Our findings suggest a correlation of the intensity and duration of menopausal symptoms with the revel of cognitive domain among menopausal women. The most significant consequences resulting from changes in the cognitive domains included psychological and vasomotor symptoms, as well as - to a lesser extent - somatic symptoms. PMID- 26677589 TI - [Intraperitoneal invasiveness of ovarian cancer from the cellular and molecular perspective]. AB - Peritoneal cavity is the primary site of ovarian cancer metastases. It is believed that the intraperitoneal invasiveness of the malignancy is determined by interactions between cancer cells and the normal peritoneal mesothelum. The nature of these interactions is, however unclear which is the reason for divergent opinions about the role of mesothelial cells in disease progression. According to some authors, the mesothelium acts as a barrier which prevents the expansion of the tumor cells. However other researchers claim that these cells actively promote various elements of cancer cell invasiveness. The aim of this study was to present both concepts of the role of the mesothelial cells in the intraperitoneal development of ovarian cancer metastases, with particular emphasis on the mechanisms of reciprocal interaction between normal and cancer cells. PMID- 26677588 TI - [Cranial ultrasound through posterolateral fontanelle in visualization of posterior fossa abnormalities in preterm and term neonates]. AB - OBJECTIVES: The aim of the study was to evaluate the usefulness of US in the diagnosis of posterior fossa abnormalities in neonates by posterolateral fontanelle as compared with the anterior fontanelle approach and MRI. MATERIAL AND METHODS: US studies were performed on 1337 neonates, including 512 preterm infants, through the anterior and posterolateral fontanelles. Abnormalities were detected in 134 patients. Among them, abnormalities in posterior fossa were visualized with the posterolateral approach in 14 neonates. MR images were obtained in that subgrqup. RESULTS: The lesions consisted of cerebellar hemorrhage and congenital cerebellar malformations. Foci of hemorrhage were visualized by US in preterm neonates (n = 5), only through the posterolateral approach and on MRI. Dandy-Walker malformations (n = 2) were detected by US with both approaches and confirmed on MRI. In pontocerebellar hypoplasia (n =2), US with both approaches, showed hypoplastic cerebellar hemispheres and fluid in the posterior fossa. MRI, additionally visualized pontine hypoplasia. Fluid collection in the posterior fossa and translocation of cerebellar hemispheres were observed in the other 6 neonates by US with both approaches. MRI revealed arachnoid cysts (n = 2), mega cisterna magna (n = 3) and Blake's pouch (n = 1). CONCLUSIONS: US using posterolateral fontanelle is the method of choice for the diagnosis of cerebellar hemorrhage. These lesions are not visualized through anterior fontanelle. US visualization of the abnormal structures in some cerebellar malformations has similar effectiveness for both approaches. MRI plays the crucial role in identification and differential diagnosis of these malformations. PMID- 26677590 TI - [Selected legal aspects of the protection of the unborn child in the light of the draft amendment to the Polish Penal Code]. AB - Criminal Law Codification Commission, acting at the Ministry of Justice prepared proposals for amendments in the Polish Penal Code, related to offenses against life and health that were presented to the public in 2013. The draft provides for the protection of the child in the prenatal stage, introducing a new category of the entity to be protected, which is "unborn child" and "unborn child able to live outside the mother's body". These regulations provide for mothers criminal liability and responsibility of the medical staff (a doctor), as well as the child's father to the extent in which he is obliged to take steps aimed at rescuing the fetus. It is doctor's responsibility to show particular care for human health and life since a doctor has special medical knowledge and that is regulated by art. 30 of the act on professions of doctor and dentist. The proposed rule changes were not brought before the legislature in the current term of the Sejm (2011-2015), but due to the development of medicine, including obstetrical ultrasound, which enables visualization of a child that moves in the womb and is treated as a separate entity with distinct personal features the grounds are given for the opinion that the issue of the legal status of the unborn child, particularly in the context of causing death of a child in the last phase before birth as a result of medical malpractice or other external factors will be back in the public discussion. PMID- 26677591 TI - [Cesarean scar pregnancy]. AB - Pregnancy in the uterine scare after previous caesarean section is the rarest type of ectopic pregnancy Due to the possibility of life-threatening complications, cesarean scar pregnancy (CSP) needs rapid and proper diagnosis and management. Hereby we present 3 cases of women with CSP, diagnosed and treated at the Department of Gynecology and Obstetrics of Jagiellonian University Medical College, in Krakow, in 2013, as well as literature review. PMID- 26677592 TI - Moving forward with five-star. PMID- 26677593 TI - State risk pools examine their missions in light of health care reform. PMID- 26677594 TI - Kidney care beyond our borders. AB - Whether it is the heartland of America or a remote village in a developing country, one overriding theme to providing care for kidney patients is person power--or the lack of it. In the developed countries, notably the U.S., Australia, New Zealand and Europe, medical schools prepare advanced practitioners who can then fill the gap left by the lack of nephrologists. However in areas where physicians are in short supply, nurses often have only basic training and trained APs are not available. In the meantime, kidney disease is taking its toll on the best and the brightest. PMID- 26677595 TI - Prospective analysis of Hemodialysis Reliable Outflow (HeRO) vascular access graft vs. cuffed catheter access in hemodialysis. AB - The Hemodialysis Reliable Outflow (HeRO) graft was compared to the cuffed catheter in end-stage renal disease patients. All consented patients were evaluated for HeRO graft placement. Eligible patients that did not receive a graft were enrolled in the control group. Participants who had not exhausted peripheral venous access sites suitable for fistulas and grafts were excluded. Differences in quality of life and incidence of bacteremia, vascular interventions, hospitalizations, and death were evaluated over one year. In thirty-three patients included in the analysis--16 HeRO, 17 control- significantly fewer bacteremia events (93.8% vs. 64.7%) and a significantly increased number of vascular interventions (64.7% vs. 25%) were reported for the HeRO versus Control group. The increased interventions in the HeRO group may be due to the two-step placement process. PMID- 26677597 TI - The democratization of medicine. AB - We can give patients the data, devices, education, and point of care access they need to 1) determine their genomic risk, 2) to manage their co-morbid conditions to delay CKD progression, 3) to manage the first 100 days of dialysis, 4) to differentiate the stress on the body with home versus in center dialysis, 5) to manage their 8-15 medications better, 6) to virtually access their health care professionals 24/7, and 7) to empower them to improve their clinical and financial outcomes. All of this is possible with technology and through the democratization of medicine. PMID- 26677596 TI - Study design is important for ESA biosimilars. AB - U.S. regulations require biosimilars to be highly similar to their reference product and demonstrate no clinically meaningful differences in safety, purity, or potency. For biosimilars of erythropoiesis-stimulating agents (ESAs), this standard is challenging--structural differences are likely, and their effect on safety and efficacy cannot be predicted from analytical studies. Thus, clinical trials should compare hemoglobin, dose, and immunogenicity endpoints. PMID- 26677599 TI - A turning point in Medicare. PMID- 26677598 TI - Nephrology registry gives specialty control of quality data. AB - It is important for providers and practices to begin working with registry level data. Submitting data to a qualified clinical data registry currently satisfies Meaningful Use Stage II menu set items. In the future, with the rollout of MIPS and the increasing focus on sharing risk, registry data will be used as a benchmark for both publicly-reported performance (the physician compare program will be linked to provider-level QCDR data) and modifications to reimbursement. It is important to remember that PQRS data is the basis for the value based modifier now and MIPS- related quality data after 2018. The RPA has launched and is evolving a unique and versatile nephrology-specific data collection and analytics tool. In collaboration with the American Society of Diagnostic and Interventional Nephrology, vascular access measures will be added to the registry for 2016. The registry and the analytics platform is a tier of software operating above your practice management system and EHR and, if data can be obtained, it can span all the locations in which nephrologists provide care. PMID- 26677600 TI - Meaningful Use Stage 3 proposed rules. PMID- 26677601 TI - CMS Open Payments program 45-day review and dispute period now open. PMID- 26677602 TI - Nature or nurture? Part I: Examining financial success in physician-owned practices. PMID- 26677603 TI - Collaboration is key to better performance. PMID- 26677604 TI - Herding cats: 4 steps to overcoming governance disorder syndrome. PMID- 26677605 TI - What's in a name? PMID- 26677606 TI - Inspiring physicians to align with organizational goals. PMID- 26677607 TI - May I? How to establish a culture of confidence. PMID- 26677608 TI - Fine-tune your skill sets to ensure a seat at the table. PMID- 26677609 TI - Personnel key to successful EHR implementation. PMID- 26677610 TI - [BIOMECHANICS STUDY ON ACETABULAR POSTERIOR WALL FRACTURE]. AB - OBJECTIVE: To study the experimental biomechanics of acetabular posterior wall fractures so as to provide theoretical basis for its clinical treatment. METHODS: Six formalin-preserved cadaveric pelvises were divided into groups A and B (n=3). The fracture models of superior-posterior wall and inferior-posterior wall of the acetabulum were created on both hips in group A; fractures were fixed with two interfragmentary screws and a locking reconstruction plate. The fracture models of superior-posterior wall of acetabulum were created on both hips in group B; fractures were fixed with two interfragmentary screws and a locking reconstruction plate at one side, and with acetabular tridimensional memory fixation system (ATMFS) at the other side. The biomechanical testing machine was used to load to 1 500 N at 10 mm/min speed for 30 seconds. The displacement of superior and inferior fracture sites was analyzed with the digital image correlation technology. RESULTS: No fracture or internal fixation breakage occurred during loading and measuring; the displacement valuess of the upper and lower fracture lines were below 2 mm (the clinically tolerable maximum value) in 2 groups. In group A, the displacement values of the upper and lower fracture lines at superior-posterior wall fracture site were significantly higher than those at inferior-posterior wall fracture site (P < 0.01), and the displacement values of the upper fracture line were significantly higher than those of lower fracture line (P < 0.01) in two fracture types. In group B, the displacement values of the upper and lower fracture lines at the side fixed with screws and a locking reconstruction plate were similar to the values at the side fixed with ATMFS, all being close to 2 mm; the displacement values of the upper fracture line were significantly higher than those of lower fracture line (P < 0.05) in two fixation types. CONCLUSION: The actual biomechanical effect of the superior posterior wall of acetabulum is much greater than that of the inferior-posterior wall of acetabulum and they should be discriminated, which might be the reasons of reduction loss, femoral head subluxation, and traumatic arthritis during follow-up. PMID- 26677611 TI - [MORPHOLOGICAL STUDY ON PROXIMAL FEMUR IN ADULT PATIENTS WITH CROWE TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP AND ITS CLINICAL SIGNIFICANCE]. AB - OBJECTIVE: To investigate the anatomical morphology of the proximal femur in adult patients with Crowe type IV developmental dysplasia of the hip (DDH) so as to provided a reference for the selection of femoral components or personalized artificial prosthesis for DDH. METHODS: Between June 2004 and December 2014, 49 patients (58 hips) with Crowe type IV DDH were included in this study. There were 7 males (8 hips) with an average age of 47.3 years and 42 females (50 hips) with an average age of 30.0 years. X-ray films were taken in all cases and CT scanning in 17 cases (17 hips). The anatomical parameters were measured through Osirix V 5.8.5 software. RESULTS: The distance of femoral head dislocation was (6.09 +/- 1.04) cm; the femoral head and neck disappeared completely in 8 hips (13.8%); femoral head atrophy and deformation and femoral neck disappearance were observed in 11 hips (19.0%). The midpoint width of the small trochanteric canal was (1.53 +/- 0.29) cm; the isthmus diameter was (0.69 +/- 0.09) cm; the canal flare index (CFI) value was (3.50 +/- 0.42) cm; the femoral neck anteversion angle was (37.0 +/- 18.2); and all indexes showed significant difference when compared with ones of normal population and Crowe type I, II, and III patients. But there was no significant difference in femoral neck-shaft angle (132.3 +/- 9.1 degrees ), isthmus height (11.66 +/- 2.67) cm (P > 0.05). The chimney type cavity (CFI < 3) accounted for 51.7%, which was significantly higher than the value of normal population. There was a positive correlation between metaphyseal CFI and CFI (r = 0.63, P = 0.00), but there was no correlation between metaphyseal CFI and distal CFI (r = -0.17, P = 0.21). CONCLUSION: The proximal femur has the morphological characteristics of narrow medullary cavity, increased anteversion angle, and high ratio of chimney type cavity, so it is necessary to design specialized femoral components or personalized artificial prosthesis for the DDH. PMID- 26677612 TI - [ANALYSIS OF IMPLANT-RELATED COMPLICATIONS AFTER HINGE KNEE REPLACEMENT FOR TUMORS AROUND THE KNEE]. AB - OBJECTIVE: To investigate the reasons and managements of implant-related complications after hinge knee replacement for tumors around the knee. METHODS: A retrospective analysis was made on the clinical data of 96 patients undergoing hinge knee replacement between January 2000 and December 2012. There were 64 males and 32 females with the mean age of 31.0 years (range, 15-72 years). The most common tumor type was osteosarcoma (72 cases), and the second was giant cell tumor (15 cases). The tumor located at the distal femurs in 52 cases and at the proximal tibias in 44 cases. Fifteen hinge and 81 rotating hinge prostheses were used. The recurrence, metastasis, and survival were recorded. The implant-related complications were observed. RESULTS: The median follow-up time was 43.5 months (range, 10-156 months). Complications were observed in 21 patients (25 implant related complications); 13 complications located at the femur and 12 complications at the tibia. The complications included aseptic loosening (8 cases), deep infection (7 cases), prosthetic breakage (4 cases), peri-prosthetic fracture (2 cases), and dislocation (4 cases). Most deep infection occurred within 12 months after operation (6/7), and most aseptic loosening after 40 months of operation (6/8). The rate of limb salvage was 90.6% (87/96) and the amputation rate was 9.4% (9/96). The overall survival rate of the prosthesis was 76.7% (5-year) and 47.2% (10-year). The 5-year survival rate was 82.9% for femoral prosthesis and 71.0% for tibial prosthesis, showing no significant difference (P = 0.954). CONCLUSION: Hinge knee prosthesis still has a high rate of complications. Deep infection is main reason to decrease short-term prosthetic survival rate, and aseptic loosening shortens the long-short prosthetic survival time. PMID- 26677613 TI - [ARTHROSCOPIC STUDY OF REMNANT-PRESERVED RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT]. AB - OBJECTIVE: To investigate the value of ligament remnant preservation during anterior cruciate ligament (ACL) reconstruction by observing the integrity, the tension, the synovial membrane covering, and the color of the reconstructed ligament under arthroscopy. METHODS: Between January 2011 and December 2013, 122 patients who underwent ACL reconstruction and arthroscopic internal fixation removal at 1 year after reconstruction were included in this study. Of these cases, 61 cases underwent ACL reconstruction using the remnant-preserved technique (preservation group); the other 61 cases underwent ACL reconstruction using non remnant-preserved technique (non preservation group). There was no significant difference in gender, age, injury side, body mass index, type of injury, the time from injury to reconstruction, and the result of KT-2000 examination between 2 groups (P > 0.05). The reconstructed ACL were observed under arthroscopy when internal fixation was removed, and the effectiveness was evaluated according to the criteria of AO Yingfang. RESULTS: In preservation group, the results were excellent in 34 cases, good in 22 cases, fair in 4 cases, and poor in 1 case; and in non preservation group, the results were excellent in 29 cases, good in 20 cases, fair in 10 cases, and poor in 2 cases; and there was no significant difference between 2 groups (Z= -1.320, P=0.187). CONCLUSION: In ACL reconstruction, the remnant-preserved technique is not obviously better than non remnant-preserved technique in the integrity, tension, membrane covering, and color. PMID- 26677614 TI - [CLINICAL STUDIES ON EFFECT OF ARTHROSCOPIC INTERCONDYLAR FOSSA ANGIOPLASTY ON ABILITY OF NEUROMUSCULAR CONTROL IN ELDERLY PATIENTS WITH KNEE OSTEOARTHRITIS]. AB - OBJECTIVE: To study the effect of arthroscopic intercondylar fossa angioplasty on the ability of neuromuscular control of the knee joint in elderly patients with knee osteoarthritis (KOA). METHODS: Between June 2012 and March 2013, 20 elderly patients with KOA and in accordance with inclusion and exclusion criteria underwent arthroscopic intercondylar fossa angioplasty (operation group), and 20 healthy elderly people served as control group. There was no significant difference in age, height, weight, and body mass index between 2 groups (P > 0.05). The proprioception capability (using passive regeneration test at measurement angles of 15, 30, and 60 degrees ) and quadriceps mobilization [including maximum voluntary contraction (MVC), central activation ratio (CAR), and activation deficit (AD)] were measured to avaluate the neuromuscular control of the knee; the Lysholm score was used to evaluate knee function. The above indexes were measured to assess the knee neuromuscular control and recovery of joint function in patients of operation group at 3, 6, and 9 months after operation. RESULTS: Compared with the control group, MVC, CAR, and Lysholm scores were significantly decreased, and the AD and passive knee angle difference were significantly increased in operation group (P < 0.05) before operation. With the time after operation, the Lysholm score, CAR, and MVC increased gradually, and the AD and the passive knee angle difference decreased gradually. There was no significant difference in the indexes between 2 groups at 9 months after operation (P > 0.05). CONCLUSION: Arthroscopic intercondylar fossa angioplasty can relieve ACL pressure, abrasion, and impact, which will recover the ability of neuromuscular control, increase proprioception and quadriceps mobilization capacity, and improve the joint function. PMID- 26677615 TI - [APPLICATION OF ONE STAGE VACUUM SEALING DRAINAGE COMBINED WITH BI-PEDICLE SLIDING FLAP TRANSPLANTATION FOR OPEN TIBIOFIBULAR FRACTURE AND SOFT TISSUE DEFECTS OF THE LOWER LEG]. AB - OBJECTIVE: To evaluate the effectiveness of one stage vacuum sealing drainage (VSD) combined with bi-pedicle sliding flap transplantation in repairing open tibiofibular fracture and soft tissue defects of the lower leg. METHODS: Twenty five patients with open tibiofibular fracture and soft tissue defects of the lower leg were treated by VSD combined with bi-pedicle sliding flap transplantation between January 2012 and July 2014. There were 18 males and 7 females, aged 12-65 years (mean, 35.2 years). The injury causes included traffic accident injury (20 cases), falling injury from height (3 cases), and heavy pound injury (2 cases). The left side was involved in 14 cases, the right side in 8 cases, and both sides in 3 cases. According to Gustilo classification, injury was rated as type II (6 lower extremities), type III a (19 lower extremities), and type III b (3 lower extremities). The anterior tibial defect area after debridement ranged from 6 cmx3 cm to 12 cmx5 cm. The course of injury and admission was 1-18 hours (mean, 4.5 hours). An anterior tibial bi-pedicle sliding flap of 24 cmx6 cm to 48 cmx8 cm was designed to cover the wound and tibia fracture was fixed with minimally invasive internal fixation. After suturing the anterior tibial wound without tension, the flap was transferred forward. The exposed fibula was fixed with reconstruction plate. The remained wound was covered by VSD. Continuously antibiotic saline irrigation was applied postoperatively. After 15 days, the VSD dressing was removed and free skin graft was used to cover the remained wound. RESULTS: After the VSD dressing was removed, the wounds and tension-reduced wound of 18 lower extremities completely healed. Unhealing wounds were covered by skin graft in 9 lower extremities. Infection occurred in 1 lower extremity and was cured after treated with antibiotics. All the wounds healed and flaps survived. The patients were followed up 6-24 months (mean, 18 months). The fractures union was confirmed by X-ray and the average union time was 3.2 months (range, 2.5-5 months). CONCLUSION: The application of one stage VSD combined with bi-pedicle sliding flap transposition is a simple and safe treatment regimen for Gustilo type II-IIIa open tibiofibular fracture and soft tissue defects of the lower leg. It has the advantages of few complications and low costs, short hospitalization, and good effectiveness. PMID- 26677616 TI - [APPLICATION RESEARCH OF USING OSTEOTOMY GUIDE DEVICE IN OSTETOMY WITH MULTIPLE DRILL HOLES]. AB - OBJECTIVE: To study the function and effectiveness of self-manufacture osteotomy guide device in osteotomy. METHODS: A guide device was manufactured, which could guide the drill and osteotome. Sixty femoral moulds which cover with bubble were used as human femurs, and a 3 cm long, 1 cm wide crack was made in the femoral moulds supracondylar to imitate operation incision. The femoral moulds were divided into 3 groups (n = 20): non-guiding group (group A), simple drill guiding group (group B), and drill-osteotome guiding group (group C). The osteotomy time, the variation range of the drill holes (incision side and the contralateral side), the variation range of the osteotome incisions (incision side and the contralateral side), and the match rate of drill holes and osteotome incision were recorded. And between February 2013 and January 2014, the osteotomy guide device was used to guide proximal tibia osteotomy in 6 patients with tibia infected nonunion to excise of infected bones. RESULTS: The osteotomy time of groups B and C was significantly less than that of group A, and it was significantly less in group C than group B (P < 0.01). The match rate of drill holes and osteotome incision in groups B and C was significantly higher than that of group A, and group C was significantly higher than group B (P < 0.05). The variation range of the drill holes in both incision side and contralateral side of groups B and C was 0, which was significantly less than that of group A (P < 0.01). The variation range of the osteotome incisions in both incision side and contralateral side of groups B and C was significantly less than that of group A, group C was significantly less than group B (P < 0.01). Preliminary clinical results showed that the osteotomy guide device was simple to use, and precise in guidance for drill and osteotome, so it could reduce the time for repeated targeting during drilling and osteoming. The osteotomy time was 8.3-11.2 minutes (mean, 9.5 minutes). The surface of osteotomy was smooth and no split; and there was rich callus formation during bone transport. Six patients were followed up 13 25 months (mean, 16 months). The bone healing index was 0.92 +/- 0.13. CONCLUSION: The osteotomy guide device can reduce the damage to surrounding tissue and bone caused by drill and osteotome, reduce the difficulty of osteotomy, and significantly shorten the cost time. PMID- 26677617 TI - [CORRELATION OF LUMBAR FACET JOINT DEGENERATION AND SPINE-PELVIC SAGITTAL BALANCE]. AB - OBJECTIVE: To investigate the relationship between lumbar facet joint degeneration of each segment and spine-pelvic sagittal balance parameters. METHODS: A retrospective analysis was made the clinical data of 120 patients with lumbar degenerative disease, who accorded with the inclusion criteria between June and November 2014. There were 58 males and 62 females with an average age of 53 years (range, 24-77 years). The disease duration ranged from 3 to 96 months (mean, 6.6 months). Affected segments included L3,4 in 32 cases, L4,5 in 47 cases, and L5, S1 in 52 cases. The CT and X-ray films of the lumbar vertebrae were taken. The facet joint degeneration was graded based on the grading system of Pathria. The spine-pelvic sagittal balance parameters were measured, including lumbar lordosis (LL), upper lumbar lordosis (ULL), lower lumbar lordosis (LLL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). According to normal range of PI, the patients were divided into 3 groups: group A (PI was less than normal range), group B (PI was within normal range), and group C (PI was more than normal range). The facet joint degeneration was compared; according to the facet joint degeneration degree, the patients were divided into group N (mild degeneration group) and group M (serious degeneration group) to observe the relationship of lumbar facet joint degeneration of each segment and spine-pelvic sagittal balance parameters. RESULTS: At L4,5 and L5, S1, facet joint degeneration showed significant difference among groups A, B, and C (P < 0.05), more serious facet joint degeneration was observed in group C; no significant difference was found in facet joint degeneration at L3,4 (P > 0.05). There was no significant difference in the other spine-pelvic sagittal balance parameters between groups N and M at each segment (P > 0.05) except for PT (P < 0.05). CONCLUSION: PI of more than normal range may lead to or aggravate lumbar facet joint degeneration at L4,5 and L5, Si; PT and PI are significantly associated with facet joint degeneration at the lower lumbar spine. PMID- 26677618 TI - [RISK FACTORS FOR INCIDENTAL DUROTOMY DURING LUMBAR SURGERY]. AB - OBJECTIVE: To evaluate the risk factors for incidental durotomy (ID) during lumbar surgery. METHODS: Eighty-six patients with ID and 86 patients with no ID (who were matched 1:1 in surgeons and surgery time) were selected from 2 235 patients who underwent lumbar surgery between January 2010 and December 2012. The gender, age, body mass index, history of smoking, alcoholism, nonsteroidal drug use, the etiology, lumbar surgery history, revision surgery, surgical approach, osteoporosis, diabetes, and surgical procedure were compared between 2 groups. Logistic regression analysis was applied to analyze the risk factors for ID. RESULTS: There was significant difference (P < 0.05) in etiology, surgical approach, revision surgery, lumbar surgery history, and surgical procedure between patients with ID and patients with no ID, which were then included in multivariate analysis. Logistic regression analysis demonstrated that lumbar surgery history, revision surgery, and minimal invasive surgery were risk factors for ID during lumbar surgery (P < 0.05). CONCLUSION: Lumbar surgery history, revision surgery, and minimal invasive surgery were risk factors for ID during lumbar surgery, thus surgery for patients with the above histories should be carefully performed to prevent ID. PMID- 26677619 TI - [EXPERIMENTAL STUDY ON POLY-AMINO ACID/NANO-HYDROXYAPATITE/CALCIUM SULFATE CAGE FOR LUMBAR INTERBODY FUSION IN GOATS]. AB - OBJECTIVE: To evaluate the effect of poly-amino acid/nano-hydroxyapatite/calcium sulfate (PHC) Cage in lumbar interbody fusion of the goat. METHODS: Eighteen mature female goats (weighing 29-33 kg) were divided into 3 groups randomly: PHC Cage group (group A), titanium Cage group (group B), and ilium group (group C). A left extraperitoneal approach was used to establish the animal model of discectomy and interbody fusion with Cage or ilium. The general situation was observed for 24 weeks after operation. X-ray films were taken to measure disc space height (DSH) before operation and at 4, 12, and 24 weeks after operation. CT three dimensional reconstuction was performed at 24 weeks after operation to evaluate the interbody fusion according to modified Brantigan grading. The specimens of L3,4 were harvested for mechanical test, histological, and scanning electron microscope (SEM) observation at 24 weeks after operation. RESULTS: All goats survived to the end of experiment. DSH at 4 weeks after operation increased when compared with preoperative one in each group, and then decreased; DSH was significantly lower at 12 and 24 weeks after operation than preoperative one in group C (P < 0.05). There was no significant difference in DSH among 3 groups at preoperation and 4 weeks after operation (P > 0.05); at 12 and 24 weeks after operation, DSH of groups A and B was significantly higher than that of group C (P < 0.05), but no significant difference was found between groups A and B (P > 0.05). CT three dimensional reconstuction showed that bony fusion was obtained in all goats of groups A and C, and in 3 goats of group B; according to modified Brantigan grading, the scores of groups A and C were significantlly higher than that of group B (P < 0.05), but no significant difference between groups A and C (P > 0.05). The biomechanical test showed that there was no significant difference in range of motion between group A and group B (P > 0.05), which were significantly lower than that of group C (P < 0.05). Microscopy and SEM observations showed that the interface between the Cage and vertebral body in group A was compact without obvious gap, and most conjunctive region was filled with osseous tissue; the interface was filled with soft tissue, and the connection was slack with obvious gap in some region in group B; the interface connection was compact, most region was filled with osseous tissue in group C. CONCLUSION: The interbody fusion with PHC Cage is effective in goat lumbar interbody fusion model. The interface connection is compact between the Cage and the host bone followed by micro-degradation of PHC Cage, but the long-term degradation need further observation. PMID- 26677620 TI - [EXPRESSION AND ROLE OF KIP1 UBIQUITYLATION-PROMOTING COMPLEX 2 IN ASTROCYTES AFTER SPINAL CORD INJURY IN RATS]. AB - OBJECTIVE: To explore the biological functions of Kip1 ubiquitylation-promoting complex 2 (KPC2) in the repair process of spinal cord injury (SCI) by studying the expression and cellular localization of KPC2 in rat SCI models. METHODS: Fifty-six adult Sprague-Dawley rats were randomly divided into 2 groups: in the control group (n = 7), simple T9 laminectomy was performed; in the experimental group (n = 49), the SCI model was established at T9, 7 rats were used to detect follow indexs at 6 hours, 12 hours, 1 day, 3 days, 5 days, 7 days, and 14 days after SC. Western blot analysis was used to detect the protein expressions of P27kip1, KPC2, CyclinA and proliferating cell nuclear antigen (PCNA) after SCI. Immunohistochemistry was used to observed the cellular localization of KPC2 after SCI, double-labeling immunofluorescence staining to observe the co-localization of KPC2 with neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP) and PCNA. In vitro astrocytes proliferation model was used to further validate these results, Western blot to detect KPC2, p27kip1, and PCNA expressions. The interaction of p27kip1, KPC1, and KPC2 in cell proliferation was analyzed by co immunoprecipitation. RESULTS: The Western blot analysis showed a significant down regulation of p27kip1 and a concomitant up-regulation of KPC2, CyclinA, and PCNA after SC. Immunohistochemistry staining revealed a wide distribution of KPC2 positive signals in the gray matter and white matter of the spinal cord. The number of KPC2 positive cells in the experimental group was significantly higher than that in the control group (t = 10.982, P = 0.000). Double-labeling immunofluorescence staining revealed the number of KPC2/NeuN co-expression cells in the gray matter of spinal cord was (0.43 +/- 0.53)/visual field in the control group and (0.57 +/- 0.53)/visual field in the experimental group, showing no significant difference (t = 0.548, P = 0.604); in the white matter of spinal cord, the number of KPC2/PCNA co-expression cells was (3.86 +/- 0.90)/visual field in the control group and (0.71 +/- 0.49)/visual field in the experimental group, showing significant difference (t = 7.778, P = 0.000). And then, the number of KPC2/PCNA co-expression cells were (0.57 +/- 0.53)/visual field in the control group and (5.57 +/- 1.13)/visual field in the experimental group, showing significant difference (t = 8.101, P = 0.000). Concomitantly, there was a similar kinetic in proliferating astrocytes in vitro. The Western blot analysis showed a significant down-regulation of p27kip1 and a concomitant up-regulation of KPC2 and PCNA after serum stimulated. Co-immunoprecipitation demonstrated increased interactions between p27kip1, KPC1, and KPC2 after stimulation. CONCLUSION: The up-regulated expression of KPC2 after SCI is related to the down-regulation of p27kip1, this event may be involved in the proliferation of astrocytes after SCI. PMID- 26677621 TI - [LONG-TERM RESULTS OF DELAYED REPAIR OF MEDIAN NERVE INJURY]. AB - OBJECTIVE: To review and analyze the long-term results of delayed repair of median nerve injury. METHODS: Between January 2004 and December 2008, 228 patients with median nerve injury undergoing delayed repair were followed up for more than 4 years, and the clinical data were retrospectively analyzed. There were 176 males (77.19%) and 52 females (22.81%), aged 2-71 years (median, 29 years). The main injury reason was cutting injury in 159 cases (69.74%); 203 cases had open injury (89.04%). According to the injury level, injury located at area I (upper arm) in 38 cases (16.67%), at area II (elbow and proximal forearm) in 53 cases (23.25%), at area III (anterior interosseous nerve) in 13 cases (5.70%), and at area IV (distal forearm to wrist) in 124 cases (54.39%). The delayed operations included delayed suture (50 cases, 21.93%), nerve release (149 cases, 65.35%), and nerve graft (29 cases, 12.72%). RESULTS: For patients with injury at area I and area II, the results were good in 23 cases (25.27%), fair in 56 cases (61.54%), and poor in 12 cases (13.18%) according to modified Birch and Raji's median nerve grading system; there was significant difference in the results between 3 repair methods for injury at area II (chi2 = 6.228, P = 0.044), but no significant difference was found for injury at area I (chi2 = 2.241, P = 0.326). Twelve patients (13.18%) needed musculus flexor functional reconstruction. Recovery of thenar muscle was poor in all patients, but only 5 cases (5.49%) received reconstruction. Thirteen cases of nerve injury at area III had good results, regardless of the repair methods. For patients with injury at area IV, the results were excellent in 6 cases (4.84%), good in 22 cases (17.74%), fair in 72 cases (58.06%), and poor in 24 cases (19.35%) according to Birch and Raji's grading system; there was significant difference in the results between 3 repair methods (chi2 = 12.646, P = 0.002), and the result of delayed repair was better. CONCLUSION: The results of delayed repair is poor for all median nerve injuries, especially for high level injury. The technique of repair methods vary with injury level. For some delayed median nerve injuries, early nerve transfer may be a better choice for indicative patients. PMID- 26677622 TI - [EFFECTIVENESS OF DEEP INFERIOR EPIGASTRIC ARTERY PERFORATOR FLAP FOR REPAIR OF PERINEAL AND PERIANAL CICATRICIAL CONTRACTURE]. AB - OBJECTIVE: To discuss the effectiveness of deep inferior epigastric artery perforator flap to repair perineal and perianal cicatricial contracture. METHODS: Between March 2007 and December 2013, 23 patients with perineal and perianal cicatricial contracture were treated with deep inferior epigastric artery perforator flap. There were 15 males and 8 females, aged from 21 to 62 years (mean, 42 years). Burn depth was III degree. The burning scars involved in the fascia, even deeper, which was rated as peripheral type (mild stenosis of the anal region and perianal cicatricial contracture) in 13 cases and as central type (severe stenosis of the anal region and anal canal with shift or defect of external genitalia) in 10 cases. All patients had limited hip abduction and squatting. Repair operation was performed at 3 months to 2 years (mean, 6 months) after wound healing. The size of soft tissue defects ranged from 10 cmx6 cm to 28 cm x 13 cm after scar excision and release. The size of flaps ranged from 12 cmx7 cm to 30 cmx15 cm. The donor site was sutured directly in 16 cases and repaired by autograft of skin in 7 cases. RESULTS: The flap had distal necrosis, distal cyanosis, and spotted necrosis in 1 case, 2 cases, and 1 case respectively, which were cured after symptomatic treatment; the other flaps survived and wound healed primarily. Twenty-one patients were followed up 6 months to 2 years (mean, 1 year). Nineteen patients had good appearance of the perinea and position of external genitalia, normal function of defecation function; stenosis of the anal region was relived, and the flaps had good texture and elasticity. Linear scar contracture was observed at the edge of flap in 2 cases, and the appearance of the perineum was restored after Z plasty. The hip abduction reached 30-40 degrees . No abdominal hernia was found at donor site. CONCLUSION: Deep inferior epigastric artery perforator flap has stable blood supply and flexible design, which is similar to the perianal and perineal tissues. The good effectiveness can be obtained to use this flap for repair of perineal and perianal cicatricial contracture. PMID- 26677623 TI - [PROTECTION EFFECTS OF BONE MARROW MESENCHYMAL STEM CELLS PARACRINE ON CHONDROCYTES INJURED BY INTERLEUKIN 1beta]. AB - OBJECTIVE: To study the potential protective effects of bone marrow mesenchymal stem cells (BMSCs) on chondrocytes injured by interleukin 1beta (IL-1beta), and the resistant capacity of chondrocytes when co-cultured indirectly with BMSCs against IL-1beta. METHODS: Six Sprague Dawley (SD) rats were randomly divided into experimental group (articular cartilage defects) and control group. The content and gene expression of IL-1beta were detected at 6 hours after surgical intervention by quantitative real time RCR (qRT-PCR) and ELISA. BMSCs repairing function test: the 18-holes cultured chondrocytes were randomly divided into 3 groups (n = 6): cells of blank group were not treated; cells of injured group and co-cultured group were intervened by IL-1beta, and Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group. The mRNA relative expressions of cysteinyl aspartate specific proteinase 3 (Caspase 3), a disintegrin and metalloprotease with Thrombospondin motifs 4 (ADAMTS-4), and ADAMTS-5 were measured via qRT-PCR in chondrocytes, meanwhile Caspase-3 content was detected via ELISA, and the cell apoptosis rate was detected via flow cytometry. BMSCs protecting function test: the 12-holes cultured chondrocytes were randomly divided into 2 groups (n=6), Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group before the 2 groups were both intervened by IL-1beta, then the same detected indexes were taken as the BMSCs repairing function test. RESULTS: Animal in vivo studies showed that relative expression of IL-1beta mRNA and IL-1beta contents were significantly higher in experimental group than control group (P < 0.05). BMSCs repair tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate were significantly higher in injured group and co-cultured group than blank group, and in injured group than co-cultured group (P < 0.05). BMSCs protect tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate in co-cultured group were significantly lower than those in control group (P < 0.05). CONCLUSION: BMSCs, as seed cells for tissue engineering, have potential for applications to anti-inflammation and anti apoptosis. PMID- 26677624 TI - [EXPERIMENTAL RESEARCH OF IMMUNE SUPPRESSION ABILITY OF HUMAN BONE MARROW MESENCHYMAL STEM CELLS DURING DIFFERENTIATION]. AB - OBJECTIVE: To study the immunogenicity of human bone marrow mesenchymal stem cells (BMSCs) and the suppression ability to the proliferation of peripheral blood mononuclear cell (PBMC) during osteogenic, chondrogenic, and adipogenic differentiations. METHODS: BMSCs were isolated from bone marrow of healthy donors and were induced to osteogenic, chondrogenic, and adipogenic differentiations for 7, 14, and 21 days. The expressions of human leukocyte antigen (HLA) class I and class II were detected by flow cytometry. PBMC were isolated from peripheral blood of healthy donors and were co-cultured with BMSCs at a ratio of 10:1 for 5 days. The suppression ability of undifferentiated and differentiated BMSCs to proliferation of PBMC were detected by flow cytometry. RESULTS: The HLA class I expression was observed but almost no expression of HLA class II was seen in undifferentiated BMSCs. There was no obviously change of the HLA class I and class II expressions during osteogenic and chondrogenic differentiations (P > 0.05), and a low expression of HLA class II was kept. The HLA class I expression gradually increased at 14 and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 and 7 days (P < 0.05); the HLA class II expression also gradually increased at 7, 14, and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 day (P < 0.05). There was no proliferation of PBMC without the stimulation of CD3 and CD28 microspheres and significant proliferation was observed when CD3 and CD28 microspheres were added, and undifferentiated BMSCs could significantly inhibit the proliferation of PBMC. There was no obvious change of the ability of BMSCs to inhibit the proliferation of PBMC during osteogenic and chondrogenic differentiations (P > 0.05); and the ability of BMSCs to inhibit the proliferation of PBMC was gradually weakened at 7, 14, and 21 days after adipogenic differentiation, showing significant differences among different time points (P < 0.05). CONCLUSION: BMSCs maintain low immunogenicity and strong immune suppression ability during osteogenic and chondrogenic differentiations, which are suitable for allogenic tissue engineering repair and cell transplantation. However, increased immunogenicity and decreased immune suppression ability after adipogenic differentiation may not be suitable for allogenic tissue engineering repair and cell transplantation. PMID- 26677625 TI - [TRANSPLANTATION OF NEURAL STEM CELLS INDUCED BY ALL-TRANS- RETINOIC ACID COMBINED WITH GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR AND CHONDROITINASE ABC FOR REPAIRING SPINAL CORD INJURY OF RATS]. AB - OBJECTIVE: To observe the effect of transplantation of neural stem cells (NSCs) induced by all-trans-retinoic acid (ATRA) combined with glial cell line derived neurotrophic factor (GDNF) and chondroitinase ABC (ChABC) on the neurological functional recovery of injured spinal cord in Sprague Dawley (SD) rats. METHODS: Sixty adult SD female rats, weighing 200-250 g, were randomly divided into 5 groups (n = 12): sham operation group (group A), SCI model group (group B), NSCs+GDNF treatment group (group C), NSCs+ChABC treatment group (group D), and NSCs+GDNF+ChABC treatment group (group E). T10 segmental transversal injury model of the spinal cord was established except group A. NSCs induced by ATRA and marked with BrdU were injected into the site of injury at 8 days after operation in groups C-E. Groups C-E were treated with GDNF, ChABC, and GDNF+ChABC respectively at 8-14 days after operation; and group A and B were treated with the same amount of saline solution. Basso Beattie Bresnahan (BBB) score and somatosensory evoked potentials (SEP) test were used to study the functional improvement at 1 day before remodeling, 7 days after remodeling, and at 1, 2, 5, and 8 weeks after transplantation. Immunofluorescence staining and HE staining were performed to observe the cells survival and differentiation in the spinal cord. RESULTS: Five mouse died but another rats were added. At each time point after modeling, BBB score of groups B, C, D, and E was significantly lower than that of group A, and SEP latent period was significantly longer than that of group A (P < 0.05), but no difference was found among groups B, C, D, and E at 7 days after remodeling and 1 week after transplantation (P > 0.05). BBB score of groups C, D, and E was significantly higher than that of group B, and SEP latent period was significantly shorter than that of group B at 2, 5, and 8 weeks after transplantation (P < 0.05); group E had higher BBB score and shorter SEP latent period than groups C and D at 5 and 8 weeks, showing significant difference (P < 0.05). HE staining showed that there was a clear boundary between gray and white matter of spinal cord and regular arrangement of cells in group A; there were incomplete vascular morphology, irregular arrangement of cells, scar, and cysts in group B; there were obvious cell hyperplasia and smaller cysts in groups C, D, and E. BrdU positive cells were not observed in groups A and B, but could be found in groups C, D and E. Group E had more positive cells than groups C and D, and difference was significant (P < 0.05). The number of glial fibrillary acidic protein positive cells of groups C, D, and E was significantly less than that of groups A and B, and it was significantly less in group E than groups C and D (P < 0.05). The number of microtubule-associated protein 2 positive cells of groups C, D, and E was significantly more than that of groups A and B, and it was significantly more in group E than groups C and D (P < 0.05). CONCLUSION: The NSCs transplantation combined with GDNF and ChABC could significantly promote the functional recovery of spinal cord injury, suggesting that GDNF and ChABC have a synergistic effect in the treatment of spinal cord injury. PMID- 26677626 TI - [FABRICATION AND BIOCOMPATIBILITY EVALUATION OF POLYURETHANE- ACELLULAR MATRIX COMPOSITE SCAFFOLD IN VITRO AND IN VIVO]. AB - OBJECTIVE: To prepare a composite scattold using bladder acellular matrix (BACM) and polyurethane (PU) for bladder repair and regeneration, and to evaluate its mechanical properties and biocompatibility. METHODS: Fresh bladder tissues were obtained from New Zealand rabbits and then treated with 1%SDS and 1%Triton X-100 to obtain BACM. The BACM was combined with PU to fabricate PU-BACM composite scaffold. The tensile strength and elongation at break of BACM and PU-BACM scaffolds were tested. Scaffolds and extracts of scaffolds were prepared to evaluate the biocompatibility. For cell-proliferation analysis, cell counting kit 8 method was used at 1, 3, 5, and 7 days after co-culture of human. bladder smooth muscle cell (HBSMC) and scaffolds. The cell cycle was tested by flow cytometry after HBSMC co-cultured with extracts of scaffolds and DMEM culture medium (control group) for 24 hours. Finally, 12 New Zealand rabbits were used to establish the model of bladder repair and regeneration. Incision of 5 mm was made on the bladder, and PU-BACM scaffold was sutured with the incision. The rabbits were sacrificed at 10, 20, 40, and 60 days after surgery to observe the inflammatory cell infiltration, new tissues formation, and regeneration of epithelium by HE staining. RESULTS: The tensile strength of BACM and PU-BACM composite scaffold was (5.78 +/- 0.85) N and (11.88 +/- 3.21) N, and elongation at break was 14.46% +/- 3.21% and 23.14% +/- 1.32% respectively, all showing significant diffeence (t = 3.182, P = 0.034; t = 4.332, P = 0.012). The cell proliferation rates of controls, PU, BACM, and PU-BACM were 36.78% +/- 1.21%, 30.49% +/- 0.89%, 18.92% +/- 0.84%, and 22.42% +/- 1.55%, it was significantly higher in PU-BACM than BACM (P < 0.05). In the bladder repair and regeneration experiment, inflammatory cell infiltration was observed at 10 days after operation, and reduced at 20 days after implantation. In the meanwhile, the degradation of scaffolds was observed in vivo. The regeneration of epithelium could be observed after 40 days of implantation. At 60 days after implantation, in situ bladder tissue formed. CONCLUSION: PU-BACM composite scaffold has higher mechanical properties and better biocompatibility than BACM scaffold. PU-BACM composite scaffold will not lead to strong immune response, and new bladder tissue can form in the in vivo rabbit bladder repair experiment. These results can provide research basis and theoretical data for further study. PMID- 26677627 TI - [PREPARATION OF BIONIC COLLAGEN-HEPARIN SULFATE SPINAL CORD SCAFFOLD WITH THREE DIMENSIONAL PRINT TECHNOLOGY]. AB - OBJECTIVE: To prepare bionic spinal cord scaffold of collagen-heparin sulfate by three-dimensional (3-D) printing, and provide a cell carrier for tissue engineering in the treatment of spinal cord injury. METHODS: Collagen- heparin sulfate hydrogel was prepared firstly, and 3-D printer was used to make bionic spinal cord scaffold. The structure was observed to measure its porosity. The scaffold was immersed in simulated body fluid to observe the quality change. The neural stem cells (NSCs) were isolated from fetal rat brain cortex of 14 days pregnant Sprague-Dawley rats and cultured. The experiment was divided into 2 groups: in group A, the scaffold was co-cultured with rat NSCs for 7 days to observe cell adhesion and morphological changes; in group B, the NSCs were cultured in 24 wells culture plate precoating with poly lysine. MTT assay was used to detect the cell viability, and immunofluorescence staining was used to identify the differentiation of NSCs. RESULTS: Bionic spinal cord scaffold was fabricated by 3-D printer successfully. Scanning electron microscope (SEM) observation revealed the micro porous structure with parallel and longitudinal arrangements and with the porosity of 90.25% +/- 2.15%. In vitro, the value of pH was not changed obviously. After 8 weeks, the scaffold was completely degraded, and it met the requirements of tissue engineering scaffolds. MTT results showed that there was no significant difference in absorbence (A) value between 2 groups at 1, 3, and 7 days after culture (P > 0.05). There were a lot of NSCs with reticular nerve fiber under light microscope in 2 groups; the cells adhered to the scaffold, and axons growth and neurosphere formation were observed in group A under SEM at 7 days after culture. The immunofluorescence staining observation showed that NSCs could differentiated into neurons and glial cells in 2 groups; the differentiation rate was 29.60% +/- 2.68% in group A and was 10.90% +/- 2.13% in group B, showing significant difference (t = 17.30, P = 0.01). CONCLUSION: The collagen-heparin sulfate scaffold by 3-D-printed has good biocompatibility and biological properties. It can promote the proliferation and differentiation of NSCs, and can used as a neural tissue engineered scaffold with great value of research and application. PMID- 26677628 TI - [HUMAN ADIPOSE-DERIVED STEM CELLS COMBINED WITH SMALL INTESNITAL SUBMUCOSA POWDER/CHITOSAN CHLORIDE-beta-GLYCEROL PHOSPHATE DISODIUM-HYDROXYETHYL CELLULOSE HYBRID FOR ADIPOSE TISSUE ENGINEERING]. AB - OBJECTIVE: To study the feasibility of human adipose-derived stem cells (hADSCs) combined with small intestinal submucosa powder (SISP)/chitosan chloride (CSCl) beta-glycerol phosphate disodium (GP)-hydroxyethyl cellulose (HEC) for adipose tissue engineering. METHODS: hADSCs were isolated from human breast fat with collagenase type I digestion, and the third passage hADSCs were mixed with SISP/CSCl-GP-HEC at a density of 1 x 10(6) cells/mL. Twenty-four healthy female nude mice of 5 weeks old were randomly divided into experimental group (n = 12) and control group (n=12), and the mice were subcutaneously injected with 1 mL hADSCs+SISP/CSCl-GP-HEC or SISP/CSCl-GP-HEC respectively at the neck. The degradation rate was evaluated by implant volume measurement at 0, 1, 2, 4, and 8 weeks. Three mice were euthanized at 1, 2, 4, and 8 weeks respectively for general, histological, and immunohistochemical observations. The ability of adipogenesis (Oil O staining), angiopoiesis (CD31), and localized the hADSCs (immunostaining for human Vimentin) were identified. RESULTS: The volume of implants of both groups decreased with time, but it was greater in experimental group than the control group, showing significant difference at 8 weeks (t = 3.348, P = 0.029). The general observation showed that the border of implants was clear with no adhesion at each time point; fat-liked new tissues were observed with capillaries on the surface at 8 weeks in 2 groups. The histological examinations showed that the structure of implants got compact gradually after injection, and SISP gradually degraded with slower degradation speed in experimental group; adipose tissue began to form, and some mature adipose tissue was observed at 8 weeks in the experimental group. The Oil O staining positive area of experimental group was greater than that of the control group at each time point, showing significant difference at 8 weeks (t = 3.41 1, P = 0.027). Immunohistochemical staining for Vemintin showed that hADSCs could survive at each time point in the experimental group; angiogenesis was most remarkable at 2 weeks, showing no significant differences in CD31 possitive area between 2 groups (P > 0.05), but angiogenesis was more homogeneous in experimental group. CONCLUSION: SISP/CSCl-GP-HEC can use as scaffolds for hADSCs to reconstruct tissue engineered adipose. PMID- 26677630 TI - [RESEARCH PROGRESS OF OSTEOCLASTS FUNCTION BEYOND BONE RESORPTION]. AB - OBJECTIVE: To review the osteoclasts (OC) function beyond bone resorption. METHODS: The related literature on OC function beyond bone resorption was reviewed, analyzed, and summarized. RESULTS: OC control the bone formation through releasing of matrix-derived growth factors, bidirectional cell-to-cell signals, and secreting OC-coupling factors, and play an important role in the niche formation, hematopoietic stem cells mobilization, and maintenance of its quantity and function; besides, OCs also regulate angiogenesis. CONCLUSION: These discoveries greatly enrich the current knowledge of OC function and open up an all-new research domain. However, the exact regulatory mechanism of OC affecting the hematopoiesis is still lack in-depth understood. Additionally, it remains to be elucidated how OC-coupling factors act on osteoblast lineage differentiation and how OC-induced angiogenesis participates in physiological and pathological processes. Unclosing the underlying mechanisms will facilitate providing scientific therapeutic strategies for treatment of many OC-related diseases. PMID- 26677629 TI - [RESEARCH PROGRESS OF CONTROLLED RELEASING DELIVERY OF BIOLOGICAL FACTORS FOR CARTILAGE REPAIR]. AB - OBJECTIVE: To summarize the recent progress of the controlled releasing delivery of biological factors for cartilage repair. METHODS: The recently published literature at home and abroad on the controlled releasing delivery of biological factors for cartilage repair was reviewed and summarized. RESULTS: Various biological factors have been applied for repairing cartilage. For better cartilage repair effects, controlled releasing delivery of biological factors can be applied by means of combining biological factors with degradable biomaterials, or by micro- and nano-particles. Meanwhile, multiple biologic delivery and temporally controlled delivery are also inevitable choices. CONCLUSION: Although lots of unsolved problems exist, the controlled releasing delivery of biological factors has been a research focus for cartilage repair because of the controllability and delicacy. PMID- 26677631 TI - Shining Our Light Brighter Than Ever: Three Years of Successful Public Relations. PMID- 26677632 TI - Tips for spiritual care-giving. PMID- 26677633 TI - The Yamas of Nursing: Ethics of Yogic Philosophy as Spiritual Practice. PMID- 26677634 TI - Beyond the Physical: Understanding Spiritual Suffering. PMID- 26677635 TI - The Essence of Spirituality~Coming Alive in Presence. PMID- 26677636 TI - Pilgrimage as a Spiritual Experience. PMID- 26677637 TI - Lessons in Love and Healing. PMID- 26677638 TI - Pregnant With Puppies. PMID- 26677639 TI - The Contribution of Segmental and Tonal Information in Mandarin Spoken Word Processing. AB - Two priming experiments examined the separate contribution of lexical tone and segmental information in the processing of spoken words in Mandarin Chinese. Experiment I contrasted four types of prime-target pairs: tone-and-segment overlap (ru4-ru4), segment-only overlap (ru3-ru4), tone-only overlap (sha4-ru4) and unrelated (qin 1 -ru4) in an auditory lexical decision task with 48 native Mandarin listeners. Experiment 2 further investigated the minimal segmental overlap needed to trigger priming when tonal information is present. Four prime target conditions were contrasted: tone-and-segment overlap (ru4-ru4), only onset segment overlap (re4-ru4), only rime overlap (pu4-ru4) and unrelated (qin 1 -ru4) in an auditory lexical decision task with 68 native Mandarin listeners. The results showed significant priming effects when both tonal and segmental information overlapped or, although to a lesser extent, when only segmental information overlapped, with no priming found when only tones matched. Moreover, any partial segmental overlap, even with matching tonal cues, resulted in significant inhibition. These data clearly indicate that lexical tones are processed differently from segments, with syllabic structure playing a critical role. These findings are discussed in terms of the overall architecture of the processing system that emerges in Mandarin lexical access. PMID- 26677640 TI - Effects of Age, Sex and Syllable Number on Voice Onset Time: Evidence from Children's Voiceless Aspirated Stops. AB - Voice onset time (VOT) is a temporal acoustic parameter that reflects motor speech coordination skills. This study investigated the patterns of age and sex differences across development of voice onset time in a group of 70 English speaking children, ranging in age from 4.1 to 18.4 years, and 12 young adults. The effect of the number of syllables on VOT patterns was also examined. Speech samples were elicited by producing syllables /pa/ and /pataka/. Results supported previous findings showing that younger children produce longer VOT values with higher levels of variability. Markedly higher VOT values and increased variability were found for boys at ages between 8 and 11 years, confirming sex differences in VOT patterns and patterns of variability. In addition, all participants consistently produced shorter VOT with higher variability for multisyllables than monosyllables, indicating an effect of syllable number. Possible explanations for these findings and clinical implications are discussed. PMID- 26677641 TI - Automaticity and Stability of Adaptation to a Foreign-Accented Speaker. AB - In three cross-modal priming experiments we asked whether adaptation to a foreign accented speaker is automatic, and whether adaptation can be seen after a long delay between initial exposure and test. Dutch listeners were exposed to a Hebrew accented Dutch speaker with two types of Dutch words: those that contained [I] (globally accented words), and those in which the Dutch [i] was shortened to [I] (specific accent marker words). Experiment 1, which served as a baseline, showed that native Dutch participants showed facilitatory priming for globally accented, but not specific accent, words. In experiment 2, participants performed a 3.5 minute phoneme monitoring task, and were tested on their comprehension of the accented speaker 24 hours later using the same cross-modal priming task as in experiment 1. During the phoneme monitoring task, listeners were asked to detect a consonant that was not strongly accented. In experiment 3, the delay between exposure and test was extended to 1 week. Listeners in experiments 2 and 3 showed facilitatory priming for both globally accented and specific accent marker words. Together, these results show that adaptation to a foreign-accented speaker can be rapid and automatic, and can be observed after a prolonged delay in testing. PMID- 26677642 TI - Inferring Difficulty: Flexibility in the Real-time Processing of Disfluency. AB - Upon hearing a disfluent referring expression, listeners expect the speaker to refer to an object that is previously unmentioned, an object that does not have a straightforward label, or an object that requires a longer description. Two visual-world eye-tracking experiments examined whether listeners directly associate disfluency with these properties of objects, or whether disfluency attribution is more flexible and involves situation-specific inferences. Since in natural situations reference to objects that do not have a straightforward label or that require a longer description is correlated with both production difficulty and with disfluency, we used a mini-artificial lexicon to dissociate difficulty from these properties, building on the fact that recently learned names take longer to produce than existing words in one's mental lexicon. The results demonstrate that disfluency attribution involves situation-specific inferences; we propose that in new situations listeners spontaneously infer what may cause production difficulty. However, the results show that these situation specific inferences are limited in scope: listeners assessed difficulty relative to their own experience with the artificial names, and did not adapt to the assumed knowledge of the speaker. PMID- 26677643 TI - Marked Initial Pitch in Questions Signals Marked Communicative Function. AB - In conversation, the initial pitch of an utterance can provide an early phonetic cue of the communicative function, the speech act, or the social action being implemented. We conducted quantitative acoustic measurements and statistical analyses of pitch in over 10,000 utterances, including 2512 questions, their responses, and about 5000 other utterances by 180 total speakers from a corpus of 70 natural conversations in 10 languages. We measured pitch at first prominence in a speaker's utterance and discriminated utterances by language, speaker, gender, question form, and what social action is achieved by the speaker's turn. Through applying multivariate logistic regression we found that initial pitch that significantly deviated from the speaker's median pitch level was predictive of the social action of the question. In questions designed to solicit agreement with an evaluation rather than information, pitch was divergent from a speaker's median predictably in the top 10% of a speakers range. This latter finding reveals a kind of iconicity in the relationship between prosody and social action in which a marked pitch correlates with a marked social action. Thus, we argue that speakers rely on pitch to provide an early signal for recipients that the question is not to be interpreted through its literal semantics but rather through an inference. PMID- 26677644 TI - Stop and Fricative Devoicing in European Portuguese, Italian and German. AB - This paper describes a cross-linguistic production study of devoicing for European Portuguese (EP), Italian, and German. We recorded all stops and fricatives in four vowel contexts and two word positions. We computed the devoicing of the time-varying patterns throughout the stop and fricative duration. Our results show that regarding devoicing behaviour, EP is more similar to German than Italian. While Italian shows almost no devoicing of all phonologically voiced consonants, both EP and German show strong and consistent devoicing through the entire consonant. Differences in consonant position showed no effect for EP and Italian, but were significantly different for German. The height of the vowel context had an effect for German and EP. For EP, we showed that a more posterior place of articulation and low vowel context lead to significantly more devoicing. However, in contrast to German, we could not find an influence of consonant position on devoicing. The high devoicing for all phonologically voiced stops and fricatives and the vowel context influence are a surprising new result. With respect to voicing maintenance, EP is more like German than other Romance languages. PMID- 26677645 TI - Consonants are More Important than Vowels in the Bouba-kiki Effect. AB - Adult listeners systematically associate certain speech sounds with round or spiky shapes, a sound-symbolic phenomenon known as the "bouba-kiki effect." In this study, we investigate the respective influences of consonants and vowels in this phenomenon. French participants were asked to match auditorily presented pseudowords with one of two visually presented shapes, one round and one spiky. The pseudowords were created by crossing either two consonant pairs with a wide range of vowels (experiment 1 and 2) or two vowel pairs with a wide range of consonants (experiment 3). Analyses showed that consonants have a greater influence than vowels in the bouba-kiki effect. Importantly, this asymmetry cannot be due to an onset bias, as a strong consonantal influence is found both with CVCV (experiment 1) and VCV (experiment 2) stimuli. We discuss these results in terms of the differential role of consonants and vowels in speech perception. PMID- 26677646 TI - Don't Listen With Your Mouth Full: The Role of Facial Motor Action in Visual Speech Perception. AB - Theories of speech perception agree that visual input enhances the understanding of speech but disagree on whether physically mimicking the speaker improves understanding. This study investigated whether facial motor mimicry facilitates visual speech perception by testing whether blocking facial motor action impairs speechreading performance. Thirty-five typically developing children (19 boys; 16 girls; M age = 7 years) completed the Revised Craig Lipreading Inventory under two conditions. While observing silent videos of 15 words being spoken, participants either held a tongue depressor horizontally with their teeth (blocking facial motor action) or squeezed a ball with one hand (allowing facial motor action). As hypothesized, blocking motor action resulted in fewer correctly understood words than that of the control task. The results suggest that facial mimicry or other methods of facial action support visual speech perception in children. Future studies on the impact of motor action on the typical and atypical development of speech perception are warranted. PMID- 26677647 TI - [Aging with vitality]. PMID- 26677648 TI - [A new, more creative approach is called for]. PMID- 26677649 TI - [Maintaining hard won independence as long as possible]. PMID- 26677650 TI - [Continued stay at home thanks to the support network]. PMID- 26677651 TI - [Overdose is just one source of danger]. PMID- 26677652 TI - [So the spark is transmitted]. PMID- 26677653 TI - [Living and working as nurses in Nambia]. PMID- 26677654 TI - [These are your rights]. PMID- 26677655 TI - [Omitting, delaying or only partly fulfilling]. PMID- 26677656 TI - [End filtration in infusion therapy]. PMID- 26677657 TI - [The strength of the network]. PMID- 26677658 TI - [Mental health, a fascinating domain]. PMID- 26677659 TI - [Implementation of a nursing care concept]. PMID- 26677660 TI - [A program in seven steps]. PMID- 26677661 TI - [A "natural" sweetener in the spotlight]. PMID- 26677662 TI - [A double challenge]. PMID- 26677663 TI - [Inheritance and innovation, Realistism and Pragmatism--A decade academic progress for Fujian Institution of Integrative Medicine]. PMID- 26677664 TI - [Chinese Medicine in Overall Modern Scientific Technologies]. AB - Chinese medicine (CM) develops with the survival, reproduction, growth, and progressing of the Chinese nation. Scientific technologies not only promote continual progressing of human societies, but also provide new ideas and methods for the development of CM. In recent years, great changes have taken place in CM complying with developing modern scientific technologies, mainly manifested in the depth of CM theories at molecular levels, the combination of syndrome differentiation and disease identification, continuous innovation and development of clinical diagnosis and treatment techniques, diversified dosages of Chinese materia medica, the academic tendency of education patterns, occupational refinement, diversified medical practice modes, and so on. PMID- 26677665 TI - [Smoothing Gan Reinforcing Shen Method Adjuvantly Treated Poor Response of Diminished Ovari- an Reserve Patients in in vitro Fertilization and Embryo Transfer: a Clinical Study]. AB - OBJECTIVE: To study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET). METHODS: Totally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups. RESULTS: The total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05). CONCLUSION: SGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos. PMID- 26677666 TI - [Effect of Qingre Yangyin Recipe on Endocrine and Metabolism of Polycystic Ovary Syndrome Patients]. AB - OBJECTIVE: To observe the effect of Qingre Yangyin Recipe (QRYYR) on sex hormones and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients. METHODS: Totally 90 PCOS patients were randomly assigned to the Chinese herbs group,the Western medicine group, the combined group, 30 in each group. Patients in the Chinese herbs group took QRYYR, one dose per day in two portions, once in the morning and once in the evening. Patients in the Western medicine group took Metformin 500 mg, twice per day for 3 consecutive months. Patients in the combined group took QRYYR and Metformin (the same as the former said two groups) in the 1st month, and took QRYYR for the following two months. Fasting blood glucose (FPG) and postprandial 2 h blood glucose (2 h GLU) were determined using hexokinase method before and after treatment. Fasting insulin (FINS), postprandial 2 h insulin (2 h INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), and testosterone (T) were detected using chemiluminescent method. Leptin and adiponectin (APN) were determined using ELISA. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Body weight and height were measured once before treatment and once after treatment to calculate body mass index (BMI). The total two-phase basal body temperature (BBT) actually obtained within 3 months was statistically collected to calculate the two-phase BBT rate. Scores for Chinese medical syndromes were compared between the two groups before and after treatment. RESULTS: Compared with before treatment in the same group, BMI, FINS, 2 h INS, HOMA-IR, leptin, LH, PRL, T, and scores for Chinese medical syndromes obviously decreased, and APN levels increased (P < 0.05). FPG and 2 h FPG obviously decreased in the Western medicine group and the combined group (P < 0.05). E2 levels obviously decreased in the combined group with statistical difference (P < 0.05). Compared with the Chinese herbs group, the difference of BMI between pre-treatment and post-treatment was more in the combined group (P < 0.05). The difference of FPG,2 h GLU, 2 h INS, HOMA-IR, and APN between pre treatment and post-treatment was more in the Chinese herbs group and the combined group (P < 0.05). Compared with the Western medicine group, the difference of PRL, T, and scores for Chinese medical syndromes was more in the Western medicine group and the combined group (P < 0.05); the difference of E2 and LH was even more in the combined group (P < 0.05). Compared with the combined group, the biphasic rate was obviously lowered in the Western medicine group (P < 0.05). CONCLUSIONS: QRYYR could improve IR but with weaker power to that of Metformin. It also could decrease serum levels of LH, T, PRL, and scores for Chinese medical syndromes, with superior effect to that of Metformin. The effect in the combined group was better. PMID- 26677667 TI - [Treatment of Anovulatory Infertility with Shen Deficiency Syndrome by ZHU's Tiaojing Cuyun Recipe: a Clinical Evaluation]. AB - OBJECTIVE: To explore the molecular biological mechanism of ZHU's Tiaojing Cuyun Recipe (TCR) for treating anovulatory infertility patients with Shen deficiency syndrome (SDS) by observing its clinical efficacy. METHODS: Using randomized blocking methods, 80 patients were assigned to the treatment group (40 cases) and the control group (40 cases). Patients with regular menstrual cycle started medication from the 5th day of menstruation. Those with irregular menstrual cycle first took progesterone till withdrawal bleeding ,and then started medication from the 5th day of vaginal bleeding. Patients in the treatment group took ZHU's TCR, one dose per day, while those in the control group took Clomifene Citrate (CC), 50 mg per day. Three menstrual cycles consisted of one therapeutic course, a total of 2 courses. Clinical efficacy such as pregnancy rates and abortion rates were observed. Ovulation indices (the maximal diameter of mature follicles, luteinized follicles, ovulational follicles, and the endometrial thickness on the ovulation day), SDS, and integrals of menstrual symptoms were monitored before and after treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) , and estradiol (E2) were determined using chemiluminescent immunoassay before treatment and after on therapeutic course. Serum levels of activin A (ACTA), inhibin B (INHB), and follistatin (FS) were detected using double antibody sandwich ELISA. RESULTS: Compared with the control group, the pregnancy rate was obviously elevated and the abortion rate was obviously lowered in the treatment group (P <0. 05). Ovulation rates of mature follicles and luteinizing follicles decreased more in the treatment group (P < 0.05). Compared with before treatment, integrals for SDS were lower, the maximal diameter of pre-ovulational follicles was increased, and integrals for menstrual symptoms in non-pregnant patients of the two groups were obviously lowered. Meanwhile, the endometrial thickness on the ovulation day was increased in the treatment group after treatment, but reduced in the control group (P < 0.05, P < 0.01). Compared with the control group, integrals for SDS were decreased, and the maximal diameter of pre-ovulational follicles was lowered in the treatment group after treatment (P < 0.05, P < 0.01). Integrals for SDS and the difference in the endometrial thickness on the ovulation day were increased, but the difference in the maximal diameter of pre-ovulational follicles were reduced (P < 0.05, P < 0.01). In the treatment group serum levels of E2 and ACTA increased more after one therapeutic course than before treatment (P < 0.01), but serum levels of INHB and FS decreased more after one therapeutic course than before treatment (P < 0.05). In the control group serum levels of FSH and ACTA increased more, and the serum level of FS decreased more after one therapeutic course than before treatment (P < 0.05, P < 0.01). Compared with the control group, serum levels of FSH and ACTA increased more, and serum levels of INHB decreased more in the treatment group after one therapeutic course than before treatment (P < 0.05, P < 0.01). CONCLUSIONS: ZHU'sTCR could improve SDS of anovulatory infertility patients, regulate the follicular development, and elevate the pregnancy rate. Its actions might be associated with regulating their sex hormones, expressions of ovary local factors such as INHB, ACTA, and FS. PMID- 26677668 TI - [Database Establishing and Data Mining of Pulmonary Diseases Based on Clinical Works by Modern Famous Veteran Doctors of Chinese Medicine]. AB - OBJECTIVE: To explore syndrome and treatment laws for treating diseases of the pulmonary system by establishing database based on clinical works by modern famous veteran doctors of Chinese medicine (CM). METHODS: Clinical experience and literature of medical records in clinical works by modern famous veteran doctors of CM were taken as data source. Database was established by fields and program design. On these bases, data mining methods such as frequency analysis, cluster analysis, factor analysis, and correlation laws were performed in syndrome and treatment laws for treating diseases of the pulmonary system. RESULTS: Established were database capable of literature searching, information statistics, data mining of modern famous veteran doctors of CM. A total of 34,414 data were input, including medical records and notes 28,045 items (81.49%) and clinical experience 6,369 items (18.51%). In medical records and notes, there were 14,048 items (50.09%) in male and 9,466 items (33.75%) in female, and the ratio of male to female was 1.48:1. There were 4,531 items (16.16%) with no marked gender in medical records or notes. Data mining such as correlation analysis, cluster analysis, factor analysis, correlation laws in more fields could be realized. CONCLUSIONS: Medical records and notes were dominated in data collected in this paper. The prevalence of pulmonary diseases was obviously higher in males than in females. The trend of concentrated manifestations in related fields for pulmonary diseases could be surfed by this database. Diagnosis and treatment laws for treating diseases of the pulmonary system could be found by various adaptive data mining targeting different fields. Multi-variables of symptoms, syndromes, prescriptions, and herbal drugs could be data mined in large samples of clinical literatures. PMID- 26677669 TI - [Treating Radiation Peumonitis by Zlyin Huoxue Granule Combined Glucocorticoids and Antibiotics: a Clinical Observation]. AB - OBJECTIVE: To observe the clinical effect of Ziyin Huoxue Granule (ZHG) combined glucocorticoids and antibiotics in treatment of radiation pneumonitis. METHODS: Totally 70 radiation pneumonitis patients were assigned to the treatment group and the control group according to random digit table, 35 in each group. All patients received glucocorticoids and antibiotics. Patients in the treatment group additionally took ZHG, one dose per day for 4 successive weeks. Watters clinical-radiologic-physiologic (CRP) score, Karnofsky Performance Status Scale (KPS) , and acute radiation injury classification [set by Radiation Therapy Oncology Group (RTOG)] were observed in the two groups before and after treatment. The application time for antibiotics and glucocorticoids was compared between the two groups. RESULTS: All patients completed this trial, and nobody dropped out or died. There was no statistical difference in Watters-CRP scores, KPS, or RTOG between the two groups before treatment (P > 0.05). Compared with before treatment in the same group, RTOG classification was obviously improved in the two groups (P < 0.05). Compared with the control group, Watters-CRP scores decreased, KPS increased, the application time for antibiotics and glucocorticoids was reduced (P < 0.05). The efficacy of RTOG classification was better in the treatment group than in the control group, but with no statistical difference between the two groups (P > 0.05). CONCLUSION: ZHG combined glucocorticoids and antibiotics was superior in treating radiation pneumonitis to using glucocorticoids or antibiotics alone in elevating Watters-CRP scores, shortening the application time for glucocorticoids and antibiotics, and improving patients' physical conditions. PMID- 26677670 TI - [Effect of Negative Emotions on Serum Levels of Adrenocorticotropic Hormones and Neuropeptide Y in Hepatitis B Liver Cirrhosis Patients]. AB - OBJECTIVE: To explore the effect of negative emotions on serum levels of adrenocorticotropic hormone (ACTH) and neuropeptide Y (NYP) in hepatitis B liver cirrhosis (HBLC) patients. METHODS: Totally 617 HBLC patients were assigned to the negative emotion group (415 cases) and the non-negative emotion group (202 cases) judged by negative emotions. Case numbers of various grading Child-Pugh were recorded in the two groups. Their liver functions were compared between the two groups. Serum levels of ACTH and NPY were detected using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the two groups. RESULTS: There was no statistical difference in Child-Pugh grading between the two groups (chi2 = 0.65, P = 0.72). Compared with the non-negative emotional group, serum ACTH levels decreased significantly in the negative emotion group with statistical difference (P < 0.05). There was no statistical difference in serum ACTH levels between the two groups (P > 0.05). CONCLUSION: The negative emotion of HBLC patients was not related to the serum ACTH level, but to relatively lower concentration serum NPY levels. PMID- 26677671 TI - [Differentiation Study of Chinese Medical Syndrome Typing for Diarrhea predominant Irritable Bowel Syndrome Based on Information of Four Chinese Medical Diagnostic Methods and Brain-gut Peptides]. AB - OBJECTIVE: To establish discriminant functions of diarrhea-predominant irritable bowel syndrome (IBS-D) by studying it from quantitative diagnosis angle, hoping to reduce interference of subjective factors in diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D. METHODS: A Chinese medical clinical epidemiological survey was carried out in 439 IBS-D patients using Clinical Information Collection Table of IBS. Initial syndromes were obtained by cluster analysis. They were analyzed using step-by-step discrimination by taking information of four Chinese medical diagnostic methods and serum brain-gut peptides (BGP) as variables. RESULTS: Clustering results were Gan stagnation Pi deficiency syndrome (GSPDS), Pi-Wei weakness syndrome (PWWS), Gan stagnation qi stasis syndrome (GSQSS), Pi-Shen yang deficiency syndrome (PSYDS), Pi-Wei damp heat syndrome (PWDHS), cold-damp disturbing Pi syndrome (CDDPS). Of them, GSPDS was mostly often seen with effective percentage of 34. 2%, while CDDPS was the least often seen with effective percentage of 5.5%. A total of 5 discriminant functions for GSPDS, PWWS, GSQSS, PSYDS, and PWDHS were obtained by step-by-step dis- crimination method. The retrospective misjudgment rate was 4.1% (16/390), while the cross-validation misjudgment rate was 15.4% (60/390). CONCLUSION: The establishment of discriminant functions is of value in objectively diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D. PMID- 26677672 TI - [Recurrence of Cerebral Infarction Associated Aspirin Resistance or Chinese Medical Constitutions: a Correlation Study]. AB - OBJECTIVE: To explore the correlation between the recurrence of cerebral infarction and aspirin resistance (AR)/Chinese medical (CM) constitutions. METHODS: Totally 413 cerebral infarction patients took Aspirin Enteric-coated Tablet (100 mg per day) while receiving routine therapy, 5 days at least in a week. They were followed-up for 12 months. Aspirin sensitivity (AS) was determined using turbidimetry. CM constitutions among patients with different AS were compared. Ratios of AR patients and AS patients of different CM constitutions in cerebral infarction recurrent patients were compared. Platelet membrane glycoproteins (GP) II b HPA-3 gene polymorphism was detected by polymerase chain reaction (PCR) method. Correlation between recurrence of cerebral infarction and AR, bb genotypes, CM constitutions times AS were analyzed by Logistic regression. RESULTS: Totally 11 patients dropped out, 101 (25.12%)with recurrent cerebral infarction and 301 (74.88%) without recurrent cerebral infarction. There were 152 (37.81%) AR patients and 250 (62.19%) AS patients. AR accounted for 26.6% (80/ 301) and AS accounted for 73.4% (221/301) in non-recurrent cerebral infarction patients. AR accounted for 71.3% (72/101) and AS accounted for 28.7% (29/101) in recurrent cerebral infarction patients. There was statistical difference in AR and AS ratios (chi2 = 64.287, P = 0.000). The proportion of yin deficiency constitution (YDC) was the largest [28.3% (43/152)] in AR patients. The proportion of blood stasis constitution (BSC) was the largest [23.6% (59/250)] in AS patients. There was statistical difference in CM constitutions between AR patients and AS patients (chi2 = 21.574, P < 0.01). The former 4 recurrent rates occurred in AR patients of YDC, BSC, damp-phlegm constitution (DPC), qi deficiency constitution (QDC). YDC occupied the first place [22.4% (34/152)]. The former 4 recurrent rates occurred in AS patients of BSC, QDC, DPC, damp-heat constitution (DHC). BSC occupied the first place [3.2% (2/250)]. Compared with non-recurrent cerebral infarction patients and AS patients, bb gene occurred most often, but aa gene and ab gene occurred obviously lesser in non-recurrent cerebral infarction patients and AR patients (chi2 = 20.171, chi2 = 55.139, P < 0.01). AR and bb gene were positively correlated with recurrent cerebral infarction (OR = 18.423, P = 0.000; OR = 1.304, P = 0.028). Body constitutions interacted with AS (OR = 0.707, P = 0.000). CONCLUSIONS: Recurrent cerebral infarction was closely related to AR and constitutional types. The recurrence rate was higher in AR patients of YDC. GP I b HPA-3 bb genotype might be a risk factor for AR and recurrent cerebral infarction. PMID- 26677674 TI - [Effect of Zhibai Dihuang Decoction on Expressions of TRPV1 and TRPV5 in Spermatogenic Cells of UU-infected Rats]. AB - OBJECTIVE: To observe the effect of Zhibai Dihuang Decoction (ZDD) on mRNA and protein expressions of transient receptor potential family vanilloid subtype 1 (TRPV1) and transient receptor potential family vanilloid subtype 5 (TRPV5) in Ureaplasma urealyticum (UU)-infected rat semens and spermatogenic cells, and to explore the pathomechanism of UU-infected infertility and the intervention of ZDD. METHODS: Totally 45 were randomly selected from 60 4-5 months old SD rats. UU testicular infected animal models were set up after bladder inoculation of UU suspension. The remaining 15 rats were simultaneously injected with normal saline as a normal control group. After a successful modeling, UU infected model rats were randomly divided into the model group, the azithromycin group, and the ZDD group, 15 in each group. Rats in the ZDD group were administered with ZDD at the daily dose of 1 g/kg by gastrogavage. Rats in the azithromycin group were administered with azithromycin suspension at the daily dose of 0. 105 mg/kg by gastrogavage. Equal volume of normal saline was administered to rats in the normal control group and the model group. All medication was performed once daily for 21 successive days. Testes and epididymis were extracted after rats were killed and UU positive rates were compared among all groups. Sperm cells were separated using a mechanical separation technique. Sperm motility parameters were detected using color sperm motion detection system. mRNA and protein expressions of TRPV1 and TRPV5 in spermatogenic cells were determined by real-time quantitative PCR and Western blot. RESULTS: The UU positive rate was obviously higher in the model group than in the normal control group [(86.7% (13/15 cases) vs. 0] P < 0.05). It was lower in the ZDD group [33.3% (5/15 cases)] and the azithromycin group [26.7% (4/15 cases)] than in the model group (P < 0.05). Compared with the normal control group, class A and B sperms were reduced, the linear velocity and the average velocity were significantly lowered, mRNA and protein expressions of TRPV1 and TRPV5 in spermated genic cells significantly decreased in the model group (P < 0.05). Compared with the model group, class A and B sperms were increased, linear and curve velocities and the average velocity were significantly elevated, mRNA and protein expressions of TRPV1 and TRPV5 significantly increased in the ZDD group and the azithromycin group (P < 0.05, P < 0.01). Compared with azithromycin group, class A and B sperms were increased, the linear velocity and the average velocity were significantly elevated, mRNA and protein expressions of TRPV1 and TRPV5 significantly increased in the ZDD group (P < 0.05, P < 0.01). CONCLUSION: ZDD could fight against UU infection and elevate semen quality, which might be associated with up-regulating mRNA and protein expressions of TRPV1 and TRPV5 in spermatogenic cells. PMID- 26677673 TI - [Effects of Bushen Wenyang Huayu Recipe on Expressions of HIF-1alpha, PHD2, and VHL in Endometriosis Rats with Shen Yang Deficiency Blood Stasis Syndrome]. AB - OBJECTIVE: To observe the effect of Bushen Wenyang Huayu Recipe (BWHR) on hypoxia inducible factor-1alpha (HIF-1alpha), proline hydroxylase2 (PHD2), von Hippel Lindau disease (VHL) suppressor gene expressions in endometriosis (EM) rats with Shen yang deficiency blood stasis syndrome (SYDBSS), and to explore the pathogenesis of EM and the mechanism of BWHR for treating EM. METHODS: Totally 50 SD rats were randomly divided into five groups, i.e., the blank control group, the sham-operation group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 in each group. Rats in the blank control group and the sham-operation group were fed routinely. Rats in the rest 3 groups received 30-day "extended refrigerator freezing and ice water immersion" and combined with " autotransplantation" to establish EM rat model with SYDBSS. One Milliliter BWHR at 3.33 g/mL was administered to rats in the CM group by gastrogavage. Gestrinone at the daily dose of 0. 5 mg/kg was administered to rats in the WM group by gastrogavage. Equal volume of normal saline was administered to rats in the model group, the blank control group, and the sham-operation group. The size and morphology of ectopic foci in rats were observed after 4 weeks of medication. Expressions of serum CA125, plasma cyclic adenosine monophosphate (cAMP), and plasma cyclic guanosine monophosphate (cGMP) were detected by radioimmunoassay. Morphological changes of eutopic endometrium and ectopic tissue were observed under the optical microscope by HE staining. Protein expressions and contents of HIF-lalpha, PHD2, and VHL were detected by immunohistochemical SABC method and Western blot. mRNA expressions of HIF-1alpha, PHD2, and VHL were detected by RT-PCR. RESULTS: The ectopic foci grew significantly in the model group. Their volumes were obviously contracted after treated by CM and WM. Compared with the blank control group and the sham operation group, serum CA125 and plasma cGMP obviously increased, cAMP obviously decreased (P < 0.05); expressions and contents of HIF-1alpha mRNA and protein all decreased (P < 0.05); mRNA and protein expressions and contents of PHD2 and VHL all decreased in the model group (P < 0.05). Compared with model group, levels of CA125 and cGMP obviously decreased; cAMP levels obviously increased, expressions and contents of HIF-1alpha mRNA and protein all increased, mRNA and protein expressions and contents of PHD2 and VHL all increased in the WM group and the CM group (P < 0.05). Compared with the CM group, PHD2 protein contents were higher in the WM group (P < 0.05). HIF-1alpha was negatively correlated with PHD2 (r = 0.799, P = 0.00). HIF-1alpha was negatively correlated with VHL (r = -0. 625, P = 0.003). CONCLUSIONS: BWHR could effectively treat EM. Its mechanism might be associated with reducing contents of HIF-1alpha, serum CA125, and plasma cGMP, and up-regulating expressions of PHD2, VHL, and cAMP. PMID- 26677675 TI - [Effect of Qianlean Pill on IL-1beta, IL-10, and TNF-alpha in Prostate Tissues of Chronic Nonbacterial Prostatitis Rats]. AB - OBJECTIVE: To observe the effect of Qianliean Pill (QP) on inflammatory factors such as IL-1beta, IL-10, and tumor necrosis factor alpha (TNF-alpha) in chronic nonbacterial prostatitis (CNP) model rats, and to explore its therapeutic mechanism. METHODS: CNP rat model was established by castration and estradiol benzoate injection. Totally 50 rats were randomly divided into 5 groups, i.e., the model group, the positive medicine group, the high dose QP group, the medium dose QP group, and the low dose QP group, 10 in each group. Besides, 10 normal rats were recruited as a normal control group. Since the 8th day of castration, Pulean Tablet (PT) at 10. 80 g/kg was administered to rats in the positive medicine group by gastrogavage. QP at 11.00, 5.50, and 2.75 g/kg was administered to rats in high, medium, and low dose QP groups by gastrogavage. Distilled water at 2 mL/100 g was administered to rats in the model group and the normal control group by gastrogavage, once daily for 30 successive days. After 30 days of medication all rats were sacrificed and their prostate tissues were extracted. The prostatic index was calculated. Pathological changes of rat prostate were observed under light microscope. Meanwhile, levels of IL-1beta, IL-10, and TNF alpha were detected using enzyme linked immunosorbent assay. RESULTS: Compared with the normal control group, the prostate index obviously decreased, levels of IL-1beta, TNF-alpha, and IL-10 in the prostate tissue significantly increased in the model group (P < 0.01). Compared with the model group, the prostate index obviously decreased in high and medium dose QP groups, and the positive medicine group (P < 0.01); levels of IL-1beta, TNF-alpha, and IL-10 obviously decreased in each QP group and the positive medicine group (P < 0.01). Compared with the positive medicine group, the TNF-alpha level decreased more obviously in the high dose QP group (P < 0.05). Compared with the normal control group, inflammatory reactions occurred obviously in rats' prostate of the model group. Compared with the model group, inflammatory reactions were milder in rats' prostate of each QP group and the positive medicine group, and their degrees were improved to some extent. CONCLUSION: QP could treat CNP, which might be achieved by regulating local immune state of the prostate, relieving inflammatory reactions of the prostate, and lowering levels of IL-beta, TNF-alpha, and IL-10 in the prostate tissue. PMID- 26677676 TI - [Effect of Chang'an No. I Recipe on 5-hydroxytryptamine Signal System and mRNA Expression Levels of Hippocampal Brain Derived Neurotrophic Factor in Visceral Hypersensitivity Rats with Irritable Bowel Syndrome]. AB - OBJECTIVE: To explore the effect of Chang'an No. I Recipe (CA) on 5 hydroxytryptamine signal system and mRNA expression levels of hippocampal brain derived neurotrophic factor (BDNF) in visceral hypersensitivity model rats with irritable bowel syndrome (IBS). METHODS: IBS visceral hypersensitivity rat models were established by combined chronic restraint stress and forced swimming. Successfully modeled rats were randomly divided into the model group, the Dicetelgroup (27 mg/kg) , the Fluoxetine group (3.6 mg/kg), the high dose CA group (22.6 mg/kg), the medium dose CA group (11.3 mg/kg), and the low dose CA group (5.7 mg/kg) according to body weight, 9 in each group. Besides, a normal control group with 10 rats was set up. Corresponding medication was administered to rats in each treatment group. Equal volume of physiological saline was administered to rats in the model group by gastrogavage. All medication was performed once per day for a total of 14 days. Pain threshold was determined by abdominal withdrawal reflex (AWR). Changes of colon 5-HT levels were determined by immunohistochemical assay. mRNA expression levels of hippocampal 5 hydroxytryptamine 1A receptor (5-HT1a) and BDNF were detected by immunofluorescent RT-PCR. RESULTS: Compared with the normal control group before treatment, pain threshold was obviously lowered in proctectasia rats of each group (P < 0.01). Compared with the normal control group after treatment, pain threshold was obviously lowered in rats of the model group; colon 5-HT levels, mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously elevated (P < 0.01). Compared with the model group, pain threshold was obviously elevated in the Fluoxetine group and all CA groups; colon 5-HT levels were obviously reduced in the Dicetel group, high and medium dose CA groups (P < 0.05, P < 0.01); mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously reduced in each CA group (P < 0.01); mRNA expression levels of hippocampal BDNF were obviously reduced in the Fluoxetine group (P < 0.01). CONCLUSIONS: The target points of CA were involved in brain and gut. CA could reduce pain threshold of proctectasia rats, down-regulate colon mucosal 5-HT levels, and lower mRNA expression levels of BDNF and 5-HT1a in rat hippocampus. PMID- 26677677 TI - [Effect of Shengjiang Xiexin Decoction on the Repair of Damaged Rat Intestinal Mucosa after Irinotecan Chemotherapy]. AB - OBJECTIVE: To explore the effect of Shengjiang Xiexin Decoction (SXD) on the intestinal mucosal and functional cells of rats after irinotecan (CPT-11) chemotherapy. METHODS: Totally 24 healthy Sprague-Dawley (SD) male rats were divided into three groups, the normal control group, the CPT-11 group, the SXD combined CPT-11 group according to random digit table, 8 in each group. CPT-11 was injected at the daily dose of 150 mg/kg to rats in the CPT-11 group and the SXD combined CPT-11 group from the caudal vein on the 4th day, once daily for 2 successive days to duplicate delayed diarrhea model. Equal volume of normal saline was injected to rats in the normal control group from the caudal vein. SXD at 2 g/mL (10 g/kg body weight) was administered to rats in the SXD combined CPT 11 group by gastrogavage for 9 successive days. Deionized water was administered to rats in the CPT-11 group and the normal control group. Diarrhea was observed at 48, 60, 72, 84, 96, and 108 h to calculate the incidence rate of diarrhea. Meanwhile, scoring for diarrhea was performed by referring methods of Akinobu Kurita. Rats were killed on day 10, ileum, cecum, and colon tissues were collected and fixed in 10% formalin solution. HE staining was performed. Intestinal mucosa injuries were graded under light microscope according to the criterion of Chiu's score. The expressions of goblet cells and Paneth cells were observed by PAS stain. Enteroendocrine cells were observed by immunohistochemical CgA staining. Positive cells were counted and cumulative optical density (IOD) analyzed by Image-Pro-Plus 6.0. RESULTS: No diarrhea occurred in rats of the normal control group at each time point. The incidence rate of diarrhea was 75.0% (6/8) at 48 h, 100.0% (8/8) at 60 h, 100.0% (8/8) at 72 h, 87.5% (7/8) at 84 h, 75.0% (6/8) at 96 h, and 75.0% (6/8) at 108 h in the CPT-11 group. The incidence rate of diarrhea was 25.0% (2/8) at 48 h, 50.0% (4/8) at 60 h, 12.5% (1/8) at 72 h, 0.0% (0/8) at 84 h in the SXD combined CPT-11 group. Compared with the same group at 60 h, scores for diarrhea at 48, 84, 96, and 108 h obviously decreased in the CPT-11 group, and scores for diarrhea at 48, 72, 84, 96, and 108 h obviously decreased in the SXD combined CPT-11 group (P < 0.05, P < 0.01). Compared with the same group at 72 h, scores for diarrhea at 84, 96, and 108 h obviously decreased in the CPT-11 group (P < 0.05, P < 0.01). Compared with the normal control group, scores for diarrhea increased in the CPT-11 group at each time point (P < 0.01); grading of ileum, cecum, and colon mucosal tissues increased (P < 0.05, P < 0.01); expressions of ileum and cecum mucosal epithelial goblet cells obviously decreased (P < 0.05); the number and expressions of ileum and cecum mucosal epithelial Paneth cells increased (P < 0.01). Expressions of ilium endocrine cells increased, while those of cecum and colon endocrine cells decreased in the CPT-11 group (P < 0.01). Compared with the CPT-11 group, scores for diarrhea were obviously lowered (P < 0.05, P < 0.01), grading of ileum, and cecum mucosal tissues decreased (P < 0.05, P < 0.01); expressions of ileum, cecum, and colon mucosal epithelial goblet cells obviously increased (P < 0.05, P < 0.01); the number and expressions of ileum cecum mucosal epithelial Paneth cells increased (P < 0.05); expressions of cecum and colon endocrine cells increased (P < 0.05, P < 0.01) in the SXD combined CPT-11 group. CONCLUSION: SXD played roles in preventing and treating CPT-11 induced delayed diarrhea by improving CPT-11 chemotherapy induced apoptosis and necrosis of intestinal mucosal and functional cells. PMID- 26677678 TI - [Prevention and Treatment of Atherosclerosis by Three Different Chinese Medical Compounds: a Mechanism Study]. AB - OBJECTIVE: To study the effect of Buyang Huanwu Decoction (BHD), Xuefu Zhuyu Decoction (XZD), and Sijunzi Decoction (SD) contained serums on expressions of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-kappaB signals, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and to explore possible anti-atherosclerotic mechanisms. METHODS: Twenty New Zealand rabbits were divided into 4 groups at random, i.e., the normal control group, the BHD group (6.7 g/kg), the XZD group (3.6 g/kg), and the SD group (1.6 g/kg), 5 in each group. All medication lasted for 7 successive days. Two h after the final medication, about 50 mL blood was withdrawn from rabbit heart for preparing serums. Human umbilical vein endothelial cell ECV304 were cultured in vitro for 18 h and randomly divided into the blank control group, the model group, the Western medicine (WM) control group, the BHD group, the XZD group, and the SD group at random. ECV304, except in the blank control group, were stimulated with lipopolysaccharide (LPS) for 2 h. Those in the WM control group and CM groups were treated respectively with corresponding CM contained serum for 24 h. Finally gene and protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor-6 (TRAF-6), NF-kappaB, LOX-1, TNF-alpha, ICAM-1, and VCAM-1 were detected by fluorescent quantitative PCR and Western blot. RESULTS: Compared with the blank control group, mRNA expressions of TLR4, MyD88, TRAF-6, NF-KB, LOX-1 , TNF cx, ICAM-1, and VCAM-1 increased significantly; protein expressions of TLR4, NF kappaB, LOX-1, TNF-alpha, ICAM-1, and VCAM-1 also increased significantly in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of each index could be significantly inhibited in the BHD group, the XZD group, and the WM control group (P < 0.05). Besides, mRNA and protein expressions of each index could be significantly elevated more in the BHD group and the XZD group than in the WM control group (P < 0.05). No statistical difference existed in each index between the SD group and the rest groups (P > 0.05). CONCLUSIONS: The mechanism of BHD and XZD for fighting against atherosclerosis might be associated with inhibiting TLR4/NF-kappaB signal transduction pathway and expressions of its downstream inflammatory factors such as LOX-1, TNF-alpha, ICAM-1, and VCAM-1. But SD showed no associated effect on atherosclerosis. PMID- 26677679 TI - [Effect of Curcumin on TGF-beta2 Regulated PPAR-gamma/PDGF-beta Signaling Pathway in Lung Fibroblasts of Mice]. AB - OBJECTIVE: To explore the effect of curcumin on TGF-beta2 regulated peroxisome proliferater activated receptor y (PPAR-gamma)/platelet derived growth factor beta (PDGF-beta) signaling pathway in lung fibroblasts of mice. METHODS: C57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-beta2, curcumin, or TGF beta2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 MUmol/L), the TGF-beta2 (10 ng/mL) group, TGF-beta2 (10 ng/mL) plus curcumin (5, 25, 50 MUmol/L) groups. mRNA expressions of PPAR-gamma, platelet-derived growth factor receptor beta (PDGFR-beta), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-gamma and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-beta2 group, the TGF-beta2 (10 ng/mL) plus curcumin 50 MUmol/L group. RESULTS: Compared with the blank control group, curcumin 50 MUmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-beta2 group, TGF-beta2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-gamma and PDGF-beta, as well as protein expression of PPAR-gamma increased, the collagen-1 expression also increased in the TGF-beta2 group (P < 0.05). Compared with the TGF-beta2 group, mRNA expressions of PPAR-gamma obviously increased in the TGF-beta2 (10 ng/mL) plus curcumin 25 MUmol/L group and the TGF-beta2 (10 ng/mL) plus curcumin 50 MUmol/L group, higher than that in the TGF-beta2 (10 ng/mL) plus curcumin 5 [MUmol/L group (P < 0.05). mRNA expressions of PPAR-gamma was higher in the TGF beta2 (10 ng/mL) plus curcumin 50 MUmol/L group than in the TGF-beta2 (10 ng/mL) plus curcumin 25 MUmol/L group (P < 0.05). mRNA expressions of PDGF-beta was lower in TGF-beta2 (10 ng/mL) plus curcumin groups than in the TGF-beta2 group (P < 0.05). Besides, PDGF-beta mRNA expressions were lower in the TGF-beta2 (10 ng/mL) plus curcumin 50 MUmol/L group than in the TGF-beta2 (10 ng/mL) plus curcumin 5 MUmol/L group and the TGF-beta2 (10 ng/mL) plus curcumin 25 MUmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-beta2 group and 3 TGF-beta2 plus curcumin groups (P > 0.05). Compared with the TGF-beta2 group, PPAR-gamma protein expressions increased and collagen-1 protein expressions decreased in the TGF-beta2 (10 ng/mL) plus curcumin 50 MULmol/L group (P < 0.05, P < 0.01). CONCLUSIONS: Curcumin not only could inhibit TGF-beta2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-gamma expressions and down-regulating PDGF-beta expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-gamma/PDGF-beta signaling pathway. PMID- 26677680 TI - [Exploring the Correlation between Pi and Shen from the Excretion of AA-I and Expressions of Or- ganic Anion Transporting Polypeptide 2al and 2 b1 in Pi Deficiency Model Rats]. AB - OBJECTIVE: To explore the correlation between Pi and Shen by observing the relationship between the metabolism of aristolochic acid (AA) and mRNA and protein expression levels of organic anion transporting polypeptide (oatp) superfamily member 2a1 and 2 b1 (oatp2al and oatp2bl) in renal, small intestinal, and large intestinal tissues of Pi deficiency syndrome (PDS) model rats. METHODS: Totally 46 Sprague-Dawley (SD) rats were randomly divided into four groups, i.e., the blank group (n = 12), the PDS group (n = 22), the AA-I group (n = 6), and the PDS AA-I group (n = 6). PDS model was established by subcutaneously injecting Reserpine at the daily dose of 5 mg/kg for 16 successive days. Carotid intubation was performed in 6 rats selected from the blank group and the PDS group. Pharmacokinetics of AA-I were detected at 5, 15, 30, 45, and 60 min after gastrogavage of AA-I. AA-I concentrations in renal, small intestinal, and large intestinal tissues of 10 rats selected from the PDS group were determined. Normal saline was administered to 6 rats selected from the PDS group and the blank group by gastrogavage. Renal, small intestinal, and large intestinal tissues were collected in the AA-I group and the PDS AA-I group at 60 min after gastrogavage of AA-I. mRNA and protein expression levels of oatp2a1 and oatp2b1 in each tissue were detected using real-time polymerase chain reaction (RT- PCR) and Western blot. RESULTS: Compared with the blank group, plasma concentrations of in vivo AA I were obviously higher in the PDS group at 15, 30, 45, and 60 min after gastrogavage of AA-I with statistical difference (P < 0.05). Plasma concentrations of AA-I were obviously decreased at 60 min after gastrogavage of AA-I; AA-I concentrations in renal and large intestinal tissues were elevated; AA I concentrations in small intestinal tissues were obviously reduced in the PDS group. There was no statistical difference in mRNA expression levels of oatp2a1 and oatp2b1 in the aforesaid three tissues of rats between the blank group and the PDS group. Compared with the blank group, mRNA expression levels of oatp2a1 and oatp2b1 decreased in small intestinal tissues of the AA-I group, and the mRNA expression level of oatp2a1 in large intestinal tissues significantly decreased (P < 0.05, P < 0.01). Compared with the PDS group, mRNA expression levels of oatp2a1 and oatp2b1 increased in renal tissues of the PDS AA-I group (P < 0.05); mRNA expression levels of oatp2b1 increased in large intestinal tissues of the PDS AA-I group (P < 0.05). CONCLUSIONS: The difference in AA-I metabolism might be associated with changed expression levels of oatp2a1 and oatp2b1 in renal, small intestinal, and large intestinal tissues under Pi deficiency induced loss of transportation. Shen and Dachang played important roles in substance metabolism under Pi deficiency state, which proved Pi-Shen correlated in Chinese medical theories. PMID- 26677681 TI - [Application of Chinese Medical Syndrome Scores in Effectiveness Evaluation: a Critical Appraisal of 240 Randomized Controlled Trials]. AB - OBJECTIVE: To explore the role of traditional Chinese medicine (TCM) syndrome scores in effectiveness evaluation of clinical studies. METHODS: Randomized controlled trials (RCTs) of TCM published in five journals in 2013 were retrieved, including Journal of Traditional Chinese Medicine (JTCM), Chinese Journal of Integrated Traditional and Western Medicine (CJITWM), Chinese Journal of Integrative Medicine (CJIM), Evidence-Based Complementary and Alternative Medicine (ECAM), and American Journal of Chinese Medicine (AJCM). The details of TCM syndrome scores and other relevant factors reported in articles were extracted and analyzed. Descriptive statistics and Chi-square test were used to describe general features of inclusive studies, ratios of reports on CM syndrome scores in each journal, formulated evidence, adopted evaluation rules, important degrees. The difference in the application rate of CM syndrome scores were compared in various diseases, diseases with or without CM syndrome typing, places where clinical studies were implemented, and different journals. RESULTS: A total of 240 RCTs were included, involving 178 published in Chinese version and 62 in English version. CM syndrome scores were used for effectiveness evaluation in 27.1% (65/240) of RCTs, of which, the highest application percentage was 35.3% (18/51) in RCTs published in CJITWM, and the lowest was 0 (0/7) in RCTs published in AJCM. There were 17 methods for grading TCM syndrome scores, of which Guideline for Clinical Research of New Chinese Herbal Medicine was most commonly used. Detailed grading standards for CM syndrome scores were reported in 46 RCTs, and CM syndrome scores were taken as primary or secondary outcomes in 6 RCTs. When describing the percentages of RCTs adopting TCM syndrome score by diseases classification, the lowest was 9.5% (2/21) in mental and behavioral disorders, and the highest was 39.1% (9/23) in endocrine, nutritional, and metabolic diseases. RCTs with TCM syndrome differentiation had a higher percentage of adopting TCM syndrome score than those without TCM syndrome differentiation (P < 0.01). Statistical differences were also found among RCTs published in Chinese core journals (32.0%), domestic science citation index (SCI) journals (28.6%), and overseas SCI journals (4.9%) (chi2 = 12.4593, P < 0.01). For RCTs conducted by Chinese scholars, the percentage of using TCM syndrome score was 32.0% in three journals from China, while 7.1% in two foreign language journals, showing significant difference (chi2 =7.3615, P < 0.01); none of RCTs conducted by foreign scholars used TCM syndrome scores for effectiveness assessment. CONCLUSIONS: There was a lack of agreeable and universal standards for TCM syndrome scores using in effectiveness evaluation. Therefore, it was not commonly used in domestic CM clinical studies. It was not so favorably agreed in overseas academic circles. PMID- 26677682 TI - [Statistical Analysis of the Acceptance for Four English Translation Versions of Huangdi Neijing]. PMID- 26677683 TI - [Research on Translation Strategies of Chinese Medicine in Traditional Cultural Context]. PMID- 26677684 TI - [Application of Chinese Medicine and Pharmacy in Tubal Infertility]. PMID- 26677686 TI - [Effect of Panax notoginseng seedlings physiological response under simulated drought stress by polyethylene glycol (PEG 6000)]. AB - The physiological effects of Panax notoginseng seedlings under simulated drought stress by PEG 6000 on antioxidant enzymes, osmotic substances and root activities were studied. The results showed that the activity of POD and APX in roots and leaves kept rising with increasing processing concentration and time. However, on the one hand, at the same processing time, SOD in roots and leaves firstly increased and then decreased with the increase of processing concentration. On the other hand, at the same processing concentration, SOD kept rising with the extension of processing time. In addition, the activity of CAT in roots and leaves tended to increase with the increasing concentration at the same processing time, while it increased at first and then decreased with the extension of time at the same concentration. The activity of SOD and APX in stem did not change obviously, whereas CAT activity in stem increased with the increasing processing time and concentration. With the increase of processing concentration and the extension of processing time, the MDA, soluble protein, proline content and root activity in leaves and roots apparently rose. Moreover, fluorescence signal of H2O2 and NO in root tip enhanced as the processing concentration increased after treated for 1 d. In summary, P. notoginseng seedlings could deal with drought stress by means of adjusting the system of antioxidant enzyme, permeating stress substances and impeded stress signal substances. Thus, when the concentration of PEG 6000 was more than 5%, it would have harm on P. notoginseng seedlings. PMID- 26677685 TI - [Physiological response and bioaccumulation of Panax notoginseng to cadmium under hydroponic]. AB - The physiological response and bioaccumulation of 2-year-old Panax notoginseng to cadmium stress was investigated under a hydroponic experiment with different cadmium concentrations (0, 2.5, 5, 10 MUmol . L(-1)). Result showed that low concentration (2.5 MUmol . L(-1)) of cadmium could stimulate the activities of SOD, POD, APX in P. notoginseng, while high concentration (10 MUmol . L(-1)) treatment made activities of antioxidant enzyme descended obviously. But, no matter how high the concentration of cadmium was, the activities of CAT were inhibited. The Pn, Tr, Gs in P. notoginseng decreased gradually with the increase of cadmium concentration, however Ci showed a trend from rise to decline. The enrichment coefficients of different parts in P. notoginseng ranked in the order of hair root > root > rhizome > leaf > stem, and all enrichment coefficients decreased with the increase of concentration of cadmium treatments; while the cadmium content in different parts of P. notoginseng and the transport coefficients rose. To sum up, cadmium could affect antioxidant enzyme system and photosynthetic system of P. notoginseng; P. notoginseng had the ability of cadmium enrichment, so we should plant it in suitable place reduce for reducing the absorption of cadmium; and choose medicinal parts properly to lessen cadmium intake. PMID- 26677687 TI - [Effects of stereoscopic cultivation on soil microorganism, enzyme activity and the agronomic characters of Panax notoginseng]. AB - Compartments of soil microorganism and enzymes between stereoscopic cultivation (three storeys) and field cultivation (CK) of Panax notoginseng were carried out, and the effects on P. notoginseng agronomic characters were also studied. Results show that concentration of soil microorganism of stereoscopic cultivation was lower than field cultivation; the activity of soil urea enzyme, saccharase and neutral phosphatase increased from lower storey to upper storey; the activity of soil urea enzyme and saccharase of lower and upper storeys were significantly lower than CK; agronomic characters of stereoscopic cultivated P. notoginsengin were inferior to field cultivation, the middle storey with the best agronomic characters among the three storeys. The correlation analysis showed that fungi, actinomycetes and neutral phosphatase were significantly correlated with P. notoginseng agronomic characters; concentration of soil fungi and bacteria were significantly correlated with the soil relative water content; actinomycete and neutral phosphatase were significantly correlated with soil pH and relative water content, respectively; the activities of soil urea enzyme and saccharase were significantly correlated with the soil daily maximum temperature difference. Inconclusion, The current research shows that the imbalance of soil microorganism and the acutely changing of soil enzyme activity were the main reasons that caused the agronomic characters of stereoscopic cultivated P. notoginseng were worse than field cultivation. Thus improves the concentration of soil microorganism and enzyme activity near to field soil by improving the structure of stereoscopic cultivation is very important. And it was the direction which we are endeavoring that built better soil ecological environment for P. notoginseng of stereoscopic cultivation. PMID- 26677688 TI - [Light and temperature and their effects on photosynthesis characteristics of stereoscopic cultivation in Panax notoginseng]. AB - Light intensity, gas temperature, soil temperature and gas exchange parameters were determined of three years old Panax notoginseng planted on different layers seedbed and different location (left, middle, right) of the same layer in greenhouse. Result show that diurnal variation of light intensity, gas temperature and soil temperature showed that upper layer > middle layer > lower layer; different locations of the same layer showed that light intensity of upper layer was not different among different locations; light intensity of middle and lower layer in right and left were the same, and significantly higher than those in the middle position; the gas temperature of each layer all with less different of each location; soil temperature of 12 cm depth is the lowest, and was gradually increased to the upper and lower surface; net photosynthetic efficiency of P. notoginseng showed that upper layer > middle layer > lower layer; there were significant correlation between soil temperature, stomatal conductance, intercellular CO2 concentration and photosynthetic rate were correlated with light intensity significantly; transpiration rates had notable correlation with light intensity and gas temperature. All above indicated that net photosynthesis rate of P. notoginseng was affected by light intensity directly, gas temperature and soil temperature indirectly. Inconclusion, stereoscopic cultivation of P. notoginseng was practicable in present study. The planting quality of P. notoginseng under stereoscopic cultivation could be improved by ameliorate the structure of seedbed to enhance the light intensity of middle and lower layer. Increase the thickness of the seedbed to decrease the temperature difference of soil. Further the management of ventilation facilities of greenhouse to control the gas temperature. PMID- 26677689 TI - [Research on output and quality of Panax notoginseng and annual change characteristics of N, P and K nutrients of planting soil under stereo cultivation]. AB - The output and agronomic characters of 3-year-old Panax notoginseng cultured under stereo structure (upper, middle and down layers) were investigated, and the annual change of N, P and K of its planting soil were also studied. Results showed that, compared with field cultured Panax notoginseng, growth vigour and output of stereo-cultivation were significantly lower. But the total production of the 3 layers was 1.6 times of field. The growth vigor and production of P. notoginseng was in the order of upper layer > middle layer > down layer. The content of ginsenoside in rhizome, root tuber and hair root of P. notoginseng was in the order of upper layer > field > middle layer > down layer. Organic matter content and pH of stereo-cultivation soil decreased with the prolonging of planting time, which with the same trend of yield. Organic matter content of stereo-cultivation soil was significantly higher than field, but the pH was significantly lower. Contents of total and available N, P and K in stereo cultivation soil and field decreased with the prolonging of planting time. The content of N and P were in the order of upper layer > middle layer > yield > down layer, the content of K was in the order of upper layer > middle layer > down layer > yield. Compared with field, the proportion of N and P in the organ of underground (rhizome, root tuber and hair root) of upper layer were increased, while decreased in middle and down layers. Proportion of K in underground decreased significantly of the 3 layers. In conclusion, the agronomic characters and production of stereo-cultivation were significantly lower than that of yield. But the total production of the 3 layers were significantly higher than field of unit area. And the aim of improving land utilization efficiency was achieved. Nutritions in the soil of stereo-cultivation were enough to support the development of P. notoginseng, which was not the cause of weak growth and low production. The absorbing ability of P. notoginseng to N, P and K nutrients was decreased by stereo-cultivation mode. So, improve the growth vigour of P. notoginseng from the perspective of adjusting the stereo-cultivation mode so as to improve the nutrient absorption capacity is the future direction. PMID- 26677690 TI - [Advances in research of volatile oil and its different chemotypes in leaves of Perilla frutescens]. AB - The volatile oil is the main component in the leaves of Perilla frutescens. According to the main types of monoterpenoids or aromatic compounds, it can be divided into different chemotypes and the main chemotypes of Chinese producing Perilla are PA type (mainly containing Perilla aldehyde and limonene), PK type (mainly containing perillaketone) and PP type (subdivided as PP-a type, with apiole as its main component; PP-m type, with myristicin as its main component; PP-e type, with elemicin as main component; PP-as type, with asarone as main component). Based on the biosynthetic pathways analysis, we also found that the formation of the particular chemotype is usually controlled by a single gene or a few genes, and different types have different pharmacological effects. In this paper, the classification under the species P. frutescens, main chemotypes of the volatile oil, and their biogenesis and regulation, pharmacological effect and influence factors are summarized and reviewed. PMID- 26677691 TI - [Advancement of colloidal gold chromatographic technique in screening of ochratoxin A]. AB - Ochratoxin A (OTA) is a toxic secondary metabolite mainly produced by Aspergillus and Penicillium species, existing in a variety of foodstuffs and Chinese medicines. OTA is difficult to be detected in practice because of the characteristics such as trace amounts, toxicity, existing in complex matrices. In the numerous detection technologies, colloidal gold chromatographic techniques are highly sensitive, specific, cost-effective and user-friendly, and are being used increasingly for OTA screening. Recently, with the development of aptamer technology and its application in chromatographic technique, a newly colloidal gold aptamer chromatographic technique has been developed. This review elaborates the structures and principles of both traditional and newly colloidal gold chromatographic techniques, focuses on newly colloidal gold aptamer chromatographic technique, summarizes and compares their use in rapid detection of OTA. Finally, in order to provide a reference for better research of related work, the development trends of this novel technique are prospected. PMID- 26677692 TI - [Advance in research on chemical constituents from Notopterygii Rhizoma et Radix]. AB - This paper summarized the recent 30 years research progress of the chemical constituents from Notopterygii Rhizoma et Radix. The chemical constituents from Notopterygii Rhizoma et Radix mainly consist of coumarins, polyene polyacetylenes, sesquiterpenes, phenolic acids, while steroids and flavonoids were less reported. All constituents were confirmed and corrected through SciFinder. We also checked the Chinese name and English name and listed the CAS number of each compound. It can provide some guidelines for the research, development and utilization of Notopterygii Rhizoma et Radix in the future. Whether there is columbianin in the Notopterygii Rhizoma et Radix need to be further researched. PMID- 26677693 TI - [Screening potential DNA barcode regions of genus Papaver]. AB - DNA barcoding is an effective technique in species identification. To determine the candidate sequences which can be used as DNA barcode to identify in Papaver genus, five potential sequences (ITS, matK, psbA-trnH, rbcL, trnL-trnF) were screened. 69 sequences were downloaded from Genbank, including 21 ITS sequences, 10 matK sequences, 8 psbA-trnH sequences, 14 rbcL sequences and 16 trnL-trnF sequences. Mega 6.0 was used to analysis the comparison of sequences. By the methods of calculating the distances in intraspecific and interspecific divergences, evaluating DNA barcoding gap and constructing NJ and UPMGA phylogenetic trees. The sequence trnL-trnF performed best. In conclusion, trnL trnF can be considered as a novel DNA barcode in Papaver genus, other four sequences can be as combination barcode for identification. PMID- 26677695 TI - [Optimization of dry granulating technique of Qibai Pingfei granule through response surface methodology]. AB - To determine the optimum process conditions for dry granulating technique of Qibai Pingfei granule, granule excipient type, rolling wheel speed and pressure and feeding speed were studied. Taking shaping rate at a time, moisture absorption and dissolubility as index, the type and amount of granule excipient were determined. In addition, taking shaping rate at a time as index, parameters of rolling wheel speed and pressure and feeding speed were researched through single factor test and response surface methodology. The optimum parameters were as follows: lactose as excipient, dry extract powder to excipient at 1:2, rolling wheel speed and pressure at 10.9 Hz and 6.4 MPa and feeding speed at 7.2 Hz. After validation of three batches pilot-scale production, the optimum processing parameters for dry granulating technique of Qibai Pingfei granule is reasonable and feasible, which can provide reliable basis for production. PMID- 26677694 TI - [Effect of beta-cyclodextrin inclusion complex on transport of major components of Xiangfu Siwu decoction essential oil in Caco-2 cell monolayer model]. AB - Although the essential oil of Xiangfu Siwu decoction (XFSWD) has strong pharmacological activity, its special physical and chemical properties restrict the clinical application and curative effect. In this paper, Xiangfu Siwu decoction essential oil (XFS-WO) was prepared by forming inclusion complex with beta-cyclodextrin (beta-CD). The present study is to investigate the effect of beta-CD inclusion complex on the transport of major components of XFSWO using Caco-2 cell monolayer model, thus to research the effect of this formation on the absorption of drugs with low solubility and high permeability, which belong to class 2 in biopharmaceutics classification system. A sensitive and rapid UPLC MS/MS method was developed for simultaneous quantification of senkyunolide A, 3-n butylphthalide, Z-ligustilide, dehydrocostus lactone and alpha-cyperone, which are active compounds in XFSWO. The transport parameters were analyzed and compared in free oil and its beta-CD inclusion complex. The result revealed that the formation of XFSWO/beta-CD inclusion complex has significantly increased the transportation and absorption of major active ingredients than free oil. Accordingly, it can be speculated that cyclodextrin inclusion complex can improve bioavailability of poorly water-soluble drugs. Above all these mentioned researches, it provided foundation and basis for physiological disposition and pharmaceutical study of XFSWD. PMID- 26677696 TI - [Investigation on quality of Haematitum and Fluoritum pieces in venalicium and study on related problems of mineral drugs]. AB - The main problems and solutions of mineral drugs in clinical use were studied based on the investigation on the quality of Haematitum and Fluoritum pieces in venalicium. The outward appearance and intrinsic quality of Haematitum and Fluoritum pieces in venalicium were studied by the requires which were in the first part of Chinese Pharmacopoeia published in 2010. The outward appearance and intrinsic quality of mineral drugs had large differences, the disqualification rate was 41.67% in 12 batches of Haematitum pieces and the disqualification rate was 53.85% in 13 batches of Fluoritum pieces. The crushing granularity of mineral drugs should be defined, the quality standards should be further improved. The drug adiministration ought to strengthen inspection and supervision in order to ensure the stability and reliability of the clinical efficacy. PMID- 26677697 TI - [Preparation and evaluation of Shedan in situ forming gel based on ocular characteristics]. AB - To develop an ophthalmic preparation of Shedan, an in situ forming gel was prepared with the formulation containing 18% of poloxamer 407 and 5% of poloxamer 188 by response surface designs plus central composite designs. The rheology results showed that LVE range gamma should limited within 0.5%, Shedan high frequency region, and the thixotropy recovery time is less than 5 seconds. The phase transition temperature was 33.25 degrees C according to curve of storage modulus and loss modulus determined by temperature scanning. Surface tension and osmometer of it determined by surface tension meter and dew point osmometer were 36.43 mN . m(-1), and 320.6 mOsm . kg(-1), respectively. Fluorescein sodium was selected as the marker to monitor the corneal residence time, and the results showed that Shedan gel could prolong drug residence for 180 min. In line with zero-order kinetics, releases of muscone and salvianolic acid B in vitro depends on gels erosion. The results of rabbit ocular irritation experiments suggested that Shedan in situ forming gel was biocompatible and nonirritant. In conclusion, a novel Shedan in situ forming gel was developed and characterized for potential drug treatment of retinal vein occlusion. PMID- 26677698 TI - [Optimization of extraction technology from Paeoniae Radix Alba using response surface methodology]. AB - To ensure the stability of chemistry components and the convenience of operation, ultrasound method was chosen to study in this investigation. As the total common peaks area in chromatograms was set to be evaluation index, the influence on the technology caused by extraction time, ethanol concentration and liquid-to-solid ratio was studied by using single factor methodology, and the extraction technology of Paeoniae Radix Alba was optimized by using response surface methodology. The results showed that the extracting results were most affected by ethanol concentration; liquid-to-solid ratio came the second and extraction time thirdly. The optimum ultrasonic-assisted extraction conditions were as follow: the ultrasonic extraction time was 20.06 min, the ethanol concentration in solvent was 72.04%, and the liquid-to-solid ratio was 53.38 mL . g(-1), the predicted value of total common peaks area was 2.1608 x 10(8). Under the extraction conditions after optimization, the total common peaks area was 2.1422 x 10(8), and the relative deviation between the measured and predicted value was 0.86%, so the optimized extraction technology for Paeoniae Radix Alba is suitable and feasible. Besides, for the purpose of extracting more sufficiently and completely, the optimized extraction technology had more advantages than the extraction method recorded in the monogragh of Paeoniae Radix Alba in Chinese Pharmacopoeia, which will come true the assessment and utilization comprehensively. PMID- 26677699 TI - [Study on totai flavonoids of Epimedium assisted with soybean polysaccharide spray-drying powder]. AB - In order to evaluate the characteristics of the spray drying of total flavonoids of Epimedium extracts assisted with soybean polysaccharide, a certain percentage of soybean polysaccharide or polyvidone were added to the total flavonoids of Epimedium extract to conduct the spray drying. The effect of soybean polysaccharides against the wall sticking effect of the spray drying was detected, as well as the powder property of total flavonoids of Epimedium spray drying powder and the dissolution in vitro behavior of the effective component. Compared with the total flavonoids of Epimedium spray drying powder, soybean polysaccharide revealed a significant anti-wall sticking effect. The spray drying power which had no notable change in the grain size made a increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior. It was worth further studying the application of soybean polysaccharide in spray drying power of traditional Chinese medicine. PMID- 26677700 TI - [Chemical constituents and cytotoxicity assay research in small polar substances from Vitis thunbergii var. taiwaniana]. AB - This article studied the chemical constituents from the aerial part of Vitis thunbergii var. taiwaniana. The 60% ethanol extract was eluted with 95% ethanol though HP-20 macroporous adsorption resin column. 12 compounds, including (1) betulinic acid, (2)2, 2, 2'-bis (4-hydroxyphenyl) propane bis (2, 3-epoxypropyl) ether, (3) eriodictyol, (4) trans-epsilon-viniferin, (5) (+)-cis-epsilon viniferin, (6) kobophenol A, (7) ampelopsin A, (8) nepalensinol B, (9) cis miyabenol C, (10) cis-vitisin B, (11) cis-gnetin H and (12) (+)-hopeaphenol, were separated by using normal phase silica gel, ODS, Sephdadex LH-20 column chromatographies and semi-preparative or preparative HPLC. Compounds 2, 5, 6, 8, 9, 10, 11 were separated from the genus Vitis for the first time and compounds 3, 7, 12 were separated from Vitis thunbergii var. taiwaniana for the first time. At a concentration of 50 MUmol . L(-1), compound 6, 7 and 11 showed strong cytotoxicity against MCF-7 cell lines with the inhibition rate of 66.58%, 57.16%, 52.84%, respectively. PMID- 26677701 TI - [Flavonoids from Selaginella uncinata]. AB - In the current study, nine flavonoids were isolated and purified from 75% ethanol extract of Selaginella uncinata (Desv.) Spring by column chromatographic techniques over macroporous resin, polyamide, silica gel, Sephadex LH-20 and pre HPLC. On the basis of their physico-chemical properties and spectroscopic data analyses, these compounds were elucidated as cirsimarin (1), nepitrin (2), apigenin-6-C-alpha-L-arabinopyranosyl-8-C-beta-D-glucopyranoside (3), apigenin-6 C-beta-D-glucopyranosyl-8-C-alpha-L-arabinopyranoside (4), apigenin-7-O-beta-D glucopyranoside (5), 2,3-dihydroamentoflavone (6), 4'-O-methylamentoflavone (7), 2,3-dihydro-4'-O-methyl-amentoflavone (8), and 2,3,2",3"-tetrahydron-4'-O-methyl robustaflavone (9). Compounds 1-5 belong to flavonoid glycosides and were isolated from the genus Selaginella for the first time. PMID- 26677702 TI - [Studies on flavonoids from Derris eriocarpa]. AB - Derris eriocarpa, a traditional Chinese medicine belonging to the family of Leguminosae, is widely distributed mainly over Yunnan, Guangxi and Guizhou of China. Modern pharmacological researches on this herb showed that it had extensive bioactivities, such as promoting urination, removing dampness and cough and reducing inspissated mucus and other biological activities. The extensive studies on the chemical constituents of this plant have resulted in the isolation of triterpenoids, steroids, fatty acid and others, but the flavone compounds haven't reported before. In our further research on the ethyl acetate of this plant, nine flavone compounds were obtained by column chromatography on silica gel, Sephadex LH-20, semi-prep HPLC, polyamide column chromatography and recrystallization for separation and purification. The structures were determined on the basis of extensive spectroscopic analysis, including MS, NMR experiments and comparison with spectroscopic data in the literature, respectively, as diosmetin (1), 3, 3'-di-O-methylquercetin (2), afromosin (3), 6, 3'-dihydroxy-7, 4'-dimethoxyisoflavone (4), odoratin (5), 7, 3'-dihydroxy-8, 4' dimethoxyisoflavone (6), 6, 4'-dihydroxy-7, 3'-dimethoxyisoflavone (7), 5, 7, 4' trihydroxy-3, 3', 5'-trimethoxyflavone (8), and alpinumisoflavone (9). All these compounds were isolated from Derris eriocarpa How for the first time. And the in vitro assays showed that compound 2 possessed moderate inhibitory activity against human cancer cells K562 and HEL. PMID- 26677703 TI - [Study on chemical constituents from seed of Oroxylum indicum]. AB - Oroxylum indicum was a traditional Chinese medicine. In order to study the chemical constituents from the seed of O. indicum, the chemical constituents of 80% methanol extract of seeds of O. indicum were subjected to chromatography on silica gel, Sephadex LH-20, and preparative HPLC, leading to the isolation of eleven compounds. The structures were identified by various spectroscopic data including ESI-MS, 1H-NMR and 13C-NMR data as oroxin B (1), chrysin (2), baicalein (3), neglectein (4), quercetin-3-O-beta-D-galactopy ranoside (5), quercetin-7-O beta-D-glucopyranoside (6), 2alpha,3beta-dihydroxylluPeol (7), lupeol (8), rengyol (9), beta-sitostero (10), and stigmasterol (11). Among them, compound 5 were firstly obtained from O. indicum. PMID- 26677704 TI - [Establishment of quality standard for Corni Fructus based on the multiple bioactive constituents]. AB - This study is to establish the methods for determination of iridoid glycosides and triterpenic acids in Corni Fructus and provide technical support for the quality control of Corni Fructus. Morroniside, loganin and sweroside were determined by HPLC-UV method with acetonitrile and 0.1% formic acid as the mobile phase, and the detective wavelength was set at 240 nm. Oleanolic acid and ursolic acid were determined by HPLC-ELSD method with methanol-0.5% ammonium acetate (87:13) as the mobile phase. The results showed that the linear ranges of morroniside, loganin and sweroside were 5.335-213.4 mg . L(-1) (r = 0.9999), 5.515-220.6 mg . L(-1) (r = 1.0000), 1.992-79.68 mg . L(-1) (r = 1.0000), respectively. The average recoveries of the above three iridoid glycosides were 98.49%-99.28% with RSDs of recoveries being less than 2%. The linear ranges of oleanolic acid and ursolic acid were 7.74-154.8 mg . L(-1) (r = 0.9964), 10.82 216.4 mg . L(-1) (r = 0.9996), respectively. The average recoveries of the above two triterpenic acids were 98.11%-99.27% with RSDs of recoveries being less than 3%. The method established in this research is simple, rapid and reliable, and can be used for quality control of Corni Fructus. Furthermore, the research provided experimental data for the improvement of present quality standard of Corni Fructus, which has important significance to guarantee its quality and clinical curative effect. PMID- 26677705 TI - [Determination of 5 nucleosides components in culture of Paecilomyces hepialid by HPLC]. AB - The concentration of 5 nucleosides, uracil, uridine, guanidine, adenine and adenosine in culture of Paecilomyces hepialid was determined by the developed method of HPLC. The HPLC method was performed on a Waters SunFire C18 (4.6 mm x 250 mm, 5 MUm) column with methanol-water gradient elution as the mobile phase. The detection wavelength was 260 nm and the colunmn temperature was controlled at 30 degrees C. The linear range was 10.00-200.00 mg . L(-1) (r = 0.9994) for uracil, 10.10-202.00 mg . L(-1) (r = 0.9992) for uridine, 10.00-200.00 mg . L(-1) (r = 0.9991) for guanidine, 10.30-206.00 mg . L(-1) (r = 0.9992) for adenine and 10.45-209.00 mg . L(-1) (r = 0.9991) for adenosine, respectively. The RSD of precision was 0.032%, 0.035%, 0.039%, 0.049%, 0.00080%, respectively. The average recoveries of uracil, guanidine, adenine, and adenosine were 97.34%, 99.10%, 101.6%, 98.61% and 100.2% with RSD of 1.3%, 2.1%, 0.96%, 0.95%, and 1.3% respectively. The method showed high sensitivity, good selectivity, linearity and repeatability, which was suitable for the content analysis of 5 nucleosides components in P. hepialid and its extracts. PMID- 26677706 TI - [Effect of puerarin on hypoxia induced proliferation of PASMCs by regulating reactive oxygen]. AB - To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether its mechanism is achieved by regulating reactive oxygen. PASMCs of primarily cultured rats (2-5 generations) were selected in the experiment. MTT, Western blot, FCM and DCFH-DA were used to observe Pue's effect the proliferation of PASMCs. The Western blot was adopted to detect whether ROS participated in Pue's effect in inhibiting PASMC proliferation. The PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Pue group, the hypoxia + Pue + Rotenone group and the hypoxia + Rotenone group, with Rotenone as the ROS blocker. According to the results, under the conditions of normoxia, Pue had no effect on the PASMC proliferation; But, under the conditions of hypoxia, it could inhibit the PASMC proliferation; Under the conditions of normoxia and hypoxia, Pue had no effect on the expression of the tumor necrosis factor-alpha (TNF-alpha) among PASMCs, could down-regulate the expression of hypoxia-induced cell cycle protein Cyclin A and proliferative nuclear antigen (PCNA). DCFH-DA proved Pue could reverse ROS rise caused by hypoxia. Both Rotenone and Pue could inhibit the up regulated expressions of HIF-1alpha, Cyclin A, PCNA caused by anoxia, with a synergistic effect. The results suggested that Pue could inhibit the hypoxia induced PASMC proliferation. Its mechanism may be achieved by regulating ROS. PMID- 26677707 TI - [Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF beta1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats]. AB - OBJECTIVE: To study the inhibitory effect of flavonoids from Glycyrrhiza uralensis on thioacetamide-induced chonic hepatic fibrosis in rats and the effect on the protein expressions of transforming growth factor-beta1 (TGF-beta1) and Caspase-3 in livers. METHOD: Male Sprague-Dawley rats were randomly divided into totally seven groups: the normal control group, the model group, LF groups s (400, 200, 100, 50 mg . kg(-1) . d(-1)) and the silymarin positive control group (30 mg . kg(-1) . d(-1)). The hepatic fibrosis model was induced in the rats through intraperitoneal injection with 3% thioacetamide (TAA) at a dose of 150 mg . kg(-1) body weight twice a week for 12 weeks. During the course, the control group and the model group were orally administered with saline (1 mL . kg(-1) . d(-1)). After the modeling and drug intervention, the pathologic changes and fibrosis in liver tissues were observed by HE staining and Masson's Trichrome staining. The serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and liver hydroxyproline (HYP) contents were assayed by biochemical process. The serum hyaluronic acid (HA) was assessed by radioimmunoassay. In addition, the protein expressions of liver TGF-beta1 and Caspase-3 were examined by immunohistochemical method. The mRNA expression of TGF beta1 in hepatic tissues was examined by quantitative Real-time PCR analysis. RESULT: Compared with the model group, flavonoids can protect the integrity of the structure of liver tissues, significantly reduce the hepatic cell degeneration and necrosis and the proliferation of fibrous tissues, notably reduce the serum AST, ALT, ALP and HA and HYP in hepatic tissues and down regulate the protein expressions of liver TGF-beta1 and Caspase-3 and the mRNA expression of TGF-beta1 in hepatic tissues. CONCLUSION: The licorice flavonoids can resist the thioacetamide-induced hepatic fibrosis in rats. Its mechanism may be related to the down-regulation of the protein expressions of TGF-beta1 and Caspase-3. PMID- 26677708 TI - [Effect of puerarin on PI3K/AKT pathway-mediated apoptosis of PASMCs]. AB - To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether the extracellular signal PI3K/AKT pathway was involved in the Pue-induced PASMC apoptosis. With the serum starvation group (SD group) as the control group, the MTT colorimetry method, Annexin V-FITC apoptosis detection kit and Western blot were used to detect Pue's effect on apoptosis of rat PASMCs. The protein immunoblot assay was used to detect whether PI3K/AKT pathway was involved in the inhibition of hypoxia-induced PASMC apoptosis process. The results show that under normoxic conditions, Pue had no effect on PASMC apoptosis; Under hypoxia conditions, Pue can inhibit PASMC apoptosis; Under normoxic and hypoxic conditions, Pue had no effect on TNF-alpha expression. Pue can reverse hypoxia induced Bcl-2 (P <0.01), up-regulate it and down-regulated Bax (P <0.01). Under normoxic conditions, Pue had no effect on P-AKT expression. Both LY294002 and Pue can inhibit hypoxia-induced Bcl-2, up-regulation of P-AKT expression and down regulation of Bax expression. Compared with the hypoxia + Pue group or the hypoxia + LY294002 group, the hypoxia + Pue + LY294002 group showed more significantly changes in Bcl-2, Bax, P-AKT expressions. The results show that, Pue can inhibit the hypoxic-induced PASMC apoptosis, which may be regulated through PI3K/AKT pathway. PMID- 26677709 TI - [Effect of echinacoside on replication and antigen expression of hepatitis B virus]. AB - To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg . kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg . kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg . L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg . L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg . kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression. PMID- 26677710 TI - [Preliminary study on effect of Rhodiolae Crenulatae Radix et Rhizoma cell wall broken decoction pieces on intestinal flora of mice]. AB - This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable. PMID- 26677711 TI - [Effect of Zhuangyao Jianshen Wan (ZYJCW) on P2X1 and P2X3 mRNA expressions in rats with diuresis caused by kidney deficiency]. AB - To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg . kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g . kg(-1) . d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g . kg(-1) . d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency. PMID- 26677712 TI - [Virtual screening for natural CETP inhibitors by structure-based pharmacophore]. AB - Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors. PMID- 26677713 TI - [Research on immune-modulation effects and its mechanisms of Guizhi Fuling capsule and its active ingredient combination]. AB - The effects of Guizhi Fuling capsule and its active ingredient combination within different concentration on SPL proliferate were observed by MTT method. The ratio of CD80/86, CD3CD25 and CD3CD69 was used to evaluate cell activation effects of Guizhi Fuling capsule and its active ingredient combination by FCM. Guizhi Fuling capsule with concentration of 400 mg . L(-1)can promote spleen lymphocyte proliferation, as well as the active ingredient combination, which showed the obvious dose-effect relationship. Compared with control group, the difference has statistical significance (P<=0.01). The result of FCM showed that Guizhi Fuling capsule and its active ingredient combination can promote CD80 and CD86 expression on spleen lymphocyte, and also can increase CD25 and CD69 ratio between spleen CD3+ cells. Compared with control group, the difference has statistical significance (P<=0.01). Thus, Guizhi Fuling capsule and its active ingredient combination may have immune-modulate effects, and the mechanism may have a close relationship with the lymphocyte activation. PMID- 26677714 TI - [Effect of Gegen Qinlian decoction on hepatic cytochrome CYP450 isozymes in rats by HPLC-MS/MS]. AB - To study the effect of Gegen Qinlian decoction and its major effective components on five hepatic microsomal CYP450 isozymes in rats. The in vitro hepatic microsomal incubation technique was used to co-culture Gegen Qinlian decoction and its major effective components together with each probe substrate. HPLC-MS/MS was used to establish the analytical method for metabolites of the five isoform probe substrates of CYP450 isozymes, detect the linearity among micoromal protein concentration, incubation time and metabolite formation amount. And HPLC-MS/MS was applied to determine the formation rate (V) of corresponding metabolites (acetaminophen, 4-OH-chlorzoxazone, dextrophan, 6-OH-chlorzoxazone and 6beta hydroxytestosterone) specific probe substrates of the five isoform probe substrates of CYP450 isozymes (phenacetin, polbutamide, dextromethorphan, chlorzoxazone, testosterone), in order to determine the activity of each isozyme. The result showed good linearity among acetaminophen, 4-OH-tolbutamide, dextrophan, 6-OH-chlorzoxazone and 6beta-hydroxytestosterone, satisfactory precision, stability and average recovery, suggesting the method was feasible. The optimized in vitro microsomal incubation conditions conformed to the requirements in the guideline of drug-drug interaction. Gegen Qinlian decoction showed different degrees of inhibitor effect on 5 CYP450 isoforms (CYP1A2, CYP2C11, CYP2D2, CYP2E1, CYP3A1/2). Its major effective component berberine could inhibit each CYP450 isoform at high concentrations (except for CYP1A2, CYP3A1/2). PMID- 26677715 TI - [Mechanism of sophocarpine in treating experimental colitis in mice]. AB - To study the preventive effect of sophocarpine (Soc) on dextran sulfate sodium (DSS)-induced colitis in mice, in order to analyze the influence of Soc on toll like receptor 4 (TLR4)/mitogen-activated protein kinases (MAPKs) and janus tyrosine kinase 2 signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathways in mice intestinal tissues. The mice was given 2.5% DSS for 6 days to induce the acute colitis model. The Soc-treated group was intraperitoneally injected with sophocarpine 30 mg . kg(-1) . d(-1) since the day before the experiment to the end. The disease activity index (DAI) was assessed everyday, and the colonic morphology and histological damage were observed with HE staining. The mRNA expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were detected by real-time RT-PCR. The changes in key protein kinase p38 mitogen-activated protein kinase (p38MAPK), c-Jun NH2-terminal protein kinase1/2 (JNK1/2), extracellular signal regulated kinase1/2 (ERK1/2), JAK2, STAT3 in TLR4/MAPKs and JAK2/STAT3 signaling pathways were detected by western blot. The result showed that the model group showed statistical significance in body weight, DAI, colon length and histopathological changes compared with the normal group (P <0.05); however, the Soc-treated group showed significant improvements in the above indexes compared with the model group (P <0.05). TNF-alpha, IL-1beta and IL-6 in the model group was significantly higher than that in the normal group (P <0.05), but lowered in the Soc-treated group to varying degrees (P <0.05). In the normal group, the expressions of TLR4 and the phosphorylation of P38, JNK1/2, JAK2, STAT3 were at low levels; in the model group, the phosphorylation of P38, JNK1/2, JAK2, STAT3 increased; the Soc-treated group showed a decrease in TLR4 expression compared with the model group, with notable declines in the phosphorylation of TLR4, P38, JNK1/2, JAK2, STAT3. These findings indicate that Soc can inhibit TLR4/MAPKs, K2/STAT3 signaling pathway activation, reduce the expression of proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 and relieve inflammatory reactions, so as to effectively prevent experimental colitis. PMID- 26677716 TI - [Absorption of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by everted intestinal sac method]. AB - To study the absorptive characteristics of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by in vitro rat everted intestinal sac model. Three representative ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et Rhizome--protocatechuic aldehyde (PAL), posmarinic acid (RA) and salvianolic acid B (SAB), were selected as the study objects. An UPLC method was established to determine and measure their cumulative absorption amount, in order to explain the absorption characteristics of ingredients in different intestinal sections. According to the experimental result, RA and SAB showed the passive absorption in ileum, which conformed to the first-order absorption rate; with low and medium doses, they showed a zero-order absorption rate in jejunum, which was reflected in the coexistence of both positive and passive absorptions; PAL showed a passive absorption manner both in ileum and jejunum. According to the experiment for absorption in different intestinal sections, RA and SAB were mainly absorbed in jejunum, while PAL was absorbed mainly in ileum. All of the three ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et rhizome -PAL, RA and SAB could be absorbed in intestines, but with differences in the absorption rate and mechanism, which indicated that the intestinal absorption of aqueous extracts from Salviae Miltiorrhizae Radix et rhizome was selectivity, instead of a simple semi-permeable membrane penetration process. PMID- 26677717 TI - [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats]. AB - This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract. PMID- 26677718 TI - [Systematic evaluation for efficacy of tripterygium glycosides in treating diabetic nephropathy stage IV]. AB - To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24 hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings. PMID- 26677719 TI - [Analysis on traditional Chinese medicine prescriptions treating cancer based on traditional Chinese medicine inheritance assistance system and discovery of new prescriptions]. AB - Malignant tumor is one of the main causes for death in the world at present as well as a major disease seriously harming human health and life and restricting the social and economic development. There are many kinds of reports about traditional Chinese medicine patent prescriptions, empirical prescriptions and self-made prescriptions treating cancer, and prescription rules were often analyzed based on medication frequency. Such methods were applicable for discovering dominant experience but hard to have an innovative discovery and knowledge. In this paper, based on the traditional Chinese medicine inheritance assistance system, the software integration of mutual information improvement method, complex system entropy clustering and unsupervised entropy-level clustering data mining methods was adopted to analyze the rules of traditional Chinese medicine prescriptions for cancer. Totally 114 prescriptions were selected, the frequency of herbs in prescription was determined, and 85 core combinations and 13 new prescriptions were indentified. The traditional Chinese medicine inheritance assistance system, as a valuable traditional Chinese medicine research-supporting tool, can be used to record, manage, inquire and analyze prescription data. PMID- 26677720 TI - [UPLC and HPLC analysis on contents of astilbin and engeletin in dong medicine "sunl gaems" of Guizhou origin by QAMS]. AB - This study aimed to simultaneously determine the contents of astilbin and engeletin in dong medicine "sunl gaems" of Guizhou origin by quantitative analysis of multi-components by single marker (QAMS), with astilbin as the internal standard substance. On UPLC and HPLC chromatograms, different models of instruments were used to investigate relative correction factors (RCF), in order to discuss the interoperability of RCFs established in different chromatographic systems. The engeletin content was calculated based on the established RCFs and compared by the one point external standard method and the external standard working curve method, in order to verify the accuracy of QAMS. According to the result, in different chromatograms, the ratios between RCF and retention time of engeletin and astilbin had a good reproducibility, with RSD between 2.0% and 1.8%, both were less than 3%. The relative differences among results of QAMS, the external standard working curve method of dong medicine "sunl gaems" ranged between 1.6% and 3.9%, with RSD between 2.02%-0.80% in line with relevant requirements and Pearson correlation coefficient at 0.9998 (P <0.01). The findings showed that QAMS was an accurate, reliable and highly reproducible method to determine the contents of astilbin and engeletin in dong medicine "sunl gaems" of Guizhou origin and so could be used to control the inherent quality of the herb. PMID- 26677721 TI - The complete mitochondrial genome of Scolopsis vosmeri and phylogenetic relationship of genus Scolopsis. AB - The complete mitogenome genome of Scolopsis vosmeri was determined in this study, which is the first recorded for the complete mitogenome in the genus Scolopsis. The circular mtDNA molecule was 16 770 bp in size and encoded 13 protein-coding genes, 2 rRNAs, 22 tRNAs and two non-coding regions, with gene arrangement and content basically identical to those of other species of Nemipteridae. The result of phylogenetic analysis strongly supported that S. vosmeri was first clustered together with genus Nemipterus and formed a monophyly in the family Nemipteridae, and then they constituted a sister-group relationship with three families Sparidae, Lethrinidae, and Lutjanidae. It concluded that the genus Scolopsis should be classified into the family Nemipteridae. The present study also revealed the phylogenetic relationship of this genus at molecular levels. PMID- 26677722 TI - Intercluster Reactions between Au25(SR)18 and Ag44(SR)30. AB - We present the first example of intercluster reactions between atomically precise, monolayer protected noble metal clusters using Au25(SR)18 and Ag44(SR)30 (RS- = alkyl/aryl thiolate) as model compounds. These clusters undergo spontaneous reaction in solution at ambient conditions. Mass spectrometric measurements both by electrospray ionization and matrix assisted laser desorption ionization show that the reaction occurs through the exchange of metal atoms and protecting ligands of the clusters. Intercluster alloying is demonstrated to be a much more facile method for heteroatom doping into Au25(SR)18, as observed by doping up to 20 Ag atoms. We investigated the thermodynamic feasibility of the reaction using DFT calculations and a tentative mechanism has been presented. Metal core-thiolate interfaces in these clusters play a crucial role in inducing these reactions and also affect rates of these reactions. We hope that our work will help accelerate activities in this area to establish chemistry of monolayer protected clusters. PMID- 26677723 TI - C(m)-History Method, a Novel Approach to Simultaneously Measure Source and Sink Parameters Important for Estimating Indoor Exposures to Phthalates. AB - The concentration of a gas-phase semivolatile organic compound (SVOC) in equilibrium with its mass-fraction in the source material, y0, and the coefficient for partitioning of an SVOC between clothing and air, K, are key parameters for estimating emission and subsequent dermal exposure to SVOCs. Most of the available methods for their determination depend on achieving steady-state in ventilated chambers. This can be time-consuming and of variable accuracy. Additionally, no existing method simultaneously determines y0 and K in a single experiment. In this paper, we present a sealed-chamber method, using early-stage concentration measurements, to simultaneously determine y0 and K. The measurement error for the method is analyzed, and the optimization of experimental parameters is explored. Using this method, y0 for phthalates (DiBP, DnBP, and DEHP) emitted by two types of PVC flooring, coupled with K values for these phthalates partitioning between a cotton T-shirt and air, were measured at 25 and 32 degrees C (room and skin temperatures, respectively). The measured y0 values agree well with results obtained by alternate methods. The changes of y0 and K with temperature were used to approximate the changes in enthalpy, DeltaH, associated with the relevant phase changes. We conclude with suggestions for further related research. PMID- 26677724 TI - The impact of self-efficacy on physical activity maintenance in patients with hip osteoarthritis - a mixed methods study. AB - PURPOSE: Understanding motivational factors related to physical activity (PA) maintenance is essential in promoting long-term exercise benefits. This study explored the impact of self-efficacy (SE) on post-intervention PA maintenance in patients with hip osteoarthritis. METHOD: An SE-theory based mixed-methods sub study of a trial investigating the effects of 4 months supervised exercise in patients with hip osteoarthritis. Questionnaire data (n = 52; baseline and 12 months) on PA and SE (Arthritis Self-Efficacy Scale, ASES, score-range 10-100) were analysed (Mann-Whitney test) for differences in characteristics of maintainers and non-maintainers. Semi-structured individual interviews (n = 15; at 12-months follow-up) were analysed using directed content analysis. RESULTS: Compared to non-maintainers (n = 9; 17%) maintainers (n = 31; 60%) had improved (p < 0.01) in median scores of ASES (Pain: +12 versus -32 points; Function: +7 versus -9 points; Other Symptoms: +11 versus -26 points) from baseline to 12 months. Experiences of possessing required skills, inspiration by other participants, encouragement from physical therapists and altered interpretations of PA-induced physiological conditions contributed to increased SE and PA maintenance. Moreover, experienced symptoms, exercise outcome expectations and obligation towards the study influenced maintenance. CONCLUSION: SE contributes to understanding of post-intervention PA maintenance in patients with hip osteoarthritis. However, disease-related factors and clinical trial participation appears significant too. Implications for Rehabilitation Patients' perceived self efficacy for physical activity contributes to the understanding of post intervention physical activity maintenance in patients with hip osteoarthritis. Practitioners may benefit from incorporating the self-efficacy theory in the planning and execution of exercise interventions to promote post-intervention physical activity maintenance and long term health benefits. Post-intervention physical activity maintenance may be increased by focussing on the patients' exercise self-efficacy through verbal persuasion and support, disease-specific information and information on normal physiological responses to exercise combined with an individualised training progression to support experiences of success and achievement of desired outcomes. PMID- 26677725 TI - Atomic and Molecular Complex Resonances from Real Eigenvalues Using Standard (Hermitian) Electronic Structure Calculations. AB - Complex eigenvalues, resonances, play an important role in a large variety of fields in physics and chemistry. For example, in cold molecular collision experiments and electron scattering experiments, autoionizing and predissociative metastable resonances are generated. However, the computation of complex resonance requires modifications of standard electronic structure codes and methods, which are not always straightforward, in addition, application of complex codes requires more computational efforts. Here we show how resonance eigenvalues, positions and widths, can be calculated using the standard, widely used, electronic-structure packages. Our method enables the calculations of the complex resonance eigenvalues by using analytical continuation procedures (such as Pade). The key point in our approach is the existence of narrow analytical passages from the real axis to the complex energy plane. In fact, the existence of these analytical passages relies on using finite basis sets. These passages become narrower as the basis set becomes more complete, whereas in the exact limit, these passages to the complex plane are closed. As illustrative numerical examples we calculated the autoionization Feshbach resonances of helium, hydrogen anion, and hydrogen molecule. We show that our results are in an excellent agreement with the results obtained by other theoretical methods and with available experimental results. PMID- 26677726 TI - Efficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groups. AB - The intracellular delivery of nucleic acids requires a vector system as they cannot diffuse across lipid membranes. Although polymeric transfecting agents have been extensively investigated, none of the proposed gene delivery vehicles fulfill all of the requirements needed for an effective therapy, namely, the ability to bind and compact DNA into polyplexes, stability in the serum environment, endosome-disrupting capacity, efficient intracellular DNA release, and low toxicity. The challenges are mainly attributed to conflicting properties such as stability vs efficient DNA release and toxicity vs efficient endosome disrupting capacity. Accordingly, investigations aimed at safe and efficient therapies are still essential to achieving gene therapy clinical success. Taking into account the mentioned issues, herein we have evaluated the DNA condensation ability of poly(ethylene oxide)113-b-poly[2-(diisopropylamino)ethyl methacrylate]50 (PEO113-b-PDPA50), poly(ethylene oxide)113-b-poly[2 (diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50), poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2 (diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47), and poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly{oligo(ethylene glycol)methyl ether methacrylate10-co-2-methylacrylic acid 2-[(2 (dimethylamino)ethyl)methylamino]ethyl ester44} (POEGMA70-b-P(OEGMA10-co-DAMA44). Block copolymers PEO113-b-PDEA50 and POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47) were evidenced to properly condense DNA into particles with a desirable size for cellular uptake via endocytic pathways (R(H) ~ 65-85 nm). The structure of the polyplexes was characterized in detail by scattering techniques and atomic force microscopy. The isothermal titration calorimetric data revealed that the polymer/DNA binding is endothermic; therefore, the process in entropically driven. The combination of results supports that POEGMA70-b-P(OEGMA10-co-DEA47-co DPA47) condenses DNA more efficiently and with higher thermodynamic outputs than does PEO113-b-PDEA50. Finally, circular dichroism spectroscopy indicated that the conformation of DNA remained the same after complexation and that the polyplexes are very stable in the serum environment. PMID- 26677728 TI - Pt Nanourchins as Efficient and Robust Counter Electrode Materials for Dye Sensitized Solar Cells. AB - This study reports on the synthesis of Pt nanourchins (PtNUs) on FTO glass surfaces and their application as an efficient and robust counter electrode (CE) in dye-sensitized solar cells (DSCs). PtNUs with sizes in the range of 100-300 nm are successfully synthesized on FTO surfaces via a simple room temperature chemical reduction of H2PtCl6 using formic acid. Note that the PtNUs have numerous Pt nanowires with 2 nm diameters and 12 nm lengths. The PtNU CE exhibits very low charge-transfer resistance for DSCs. The efficiency of DSCs fabricated with PtNU CEs is 9.39%, which is higher than that of devices assembled with Pt sputtered CEs (8.51%). PMID- 26677727 TI - Complete mitochondrial genome sequence of the pelagic chaetognath, sagitta ferox. AB - Sagitta ferox is an important group of transparent marine metazoans in marine pelagic food webs, the diversity study of S. ferox in nature ecosystem is important. In this study, we report the complete mitochondrial genome sequences of S. ferox. Its complete mtDNA sequence is 12 153 bp in length, which contains 11 protein-coding genes, 11 transfer RNA genes, and 2 ribosomal RNA genes. The composition of A, T, G, and C in mtDNA is 30.23%, 28.39%, 22.13%, and 19.25%, respectively. The percentage of A + T is 58.62%. The complete mitogenome of S. ferox could be applied in the studies of biodiversity researches, molecular systematics, and the evaluation of marine ecological environment. PMID- 26677729 TI - Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells. AB - Novel 1,5-diphenyl-6-substituted-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones were synthesized and characterized. All compounds were screened for their anti proliferative activities in five different cancer cell lines. The results showed that compounds 7a and 7b comprising aminoguanidino or guanidino moiety at position 6 inhibited proliferation of RKO colon cancer cells with IC50 of 8 and 4 MUM, respectively. Compounds 7a and 7b induced apoptosis in RKO cells, which was confirmed by TUNEL and annexin V-FITC assays. Flow cytometric analysis indicated that compounds 7a and 7b arrested RKO cells in the G1 phase and the most active compound 7b increased levels of p53, p21, Bax, ERK1/2 and reduced levels of Bcl2 and Akt. Compound 7b also activates release of cytochrome c, which is consistent with activation of caspase-9. Additionally, compound 7b increased caspase-3 activity and cleaved PARP-1 in RKO cells. Collectively, these findings could establish a molecular basis for the development of new anti-cancer agents. PMID- 26677730 TI - Proper Evaluation of Factors Affecting Oxidative Status. PMID- 26677732 TI - Re-work: a new Japanese support system for reinstatement. AB - Re-work is a new treatment technique that follows the conventional Japanese approach, which includes rest and pharmacotherapy. The aim of re-work is to prevent repeated sick leave by helping individuals reflect on the reasons behind the sick leave and improve stress-related coping skills. Re-work participants prepare in an environment similar to their workplaces at a medical institution or a specialised public facility for several months before returning to work. As re work is undertaken via group work, this has benefits beyond those which can be achieved by an individual alone. The reinstatement effects of re-work are now starting to be verified. Issues of interest for re-work include its unified concept-based programme, and the need to further verify its clinical efficacy and cost-effectiveness. PMID- 26677731 TI - Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage. AB - BACKGROUND: Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. METHODS: This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. RESULTS: The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. CONCLUSIONS: Among the genes reported by PCA based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study. PMID- 26677734 TI - Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy. PMID- 26677733 TI - Increased activities of both superoxide dismutase and catalase were indicators of acute depressive episodes in patients with major depressive disorder. AB - Oxidative stress may play an important role in the pathophysiology of major depressive disorder (MDD). The aim of this study was to investigate the serum levels of oxidative stress biomarkers and S100B in patients with MDD in an acute phase, and evaluate the changes in superoxide dismutase (SOD), protein carbonyl content (PCC), glutathione peroxidase (GPX), 8-hydroxy 2'-deoxyguanosine after treatment (8-OHdG), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and S100B. We consecutively enrolled 21 MDD inpatients in an acute phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. Serum SOD and CAT activities in MDD patients in an acute phase were significantly higher than those of healthy subjects, and serum PCC levels were significantly lower. The HAM-D scores had a significantly positive association with S100B levels. Eighteen depressed patients were followed up, and there was no significant difference among all of the markers after treatment. In conclusion, our results suggest that increased activities of both SOD and CAT might be indicators of acute depressive episodes in MDD patients. PMID- 26677735 TI - Relations among Social Anxiety, Eye Contact Avoidance, State Anxiety, and Perception of Interaction Performance during a Live Conversation. AB - There is building evidence that highly socially anxious (HSA) individuals frequently avoid making eye contact, which may contribute to less meaningful social interactions and maintenance of social anxiety symptoms. However, research to date is lacking in ecological validity due to the usage of either static or pre-recorded facial stimuli or subjective coding of eye contact. The current study examined the relationships among trait social anxiety, eye contact avoidance, state anxiety, and participants' self-perceptions of interaction performance during a live, four-minute conversation with a confederate via webcam, and while being covertly eye-tracked. Participants included undergraduate women who conversed with same-sex confederates. Results indicated that trait social anxiety was inversely related to eye contact duration and frequency averaged across the four minutes, and positively related to state social anxiety and negative self-ratings. In addition, greater anticipatory state anxiety was associated with reduced eye contact throughout the first minute of the conversation. Eye contact was not related to post-task state anxiety or self perception of poor performance; although, trends emerged in which these relations may be positive for HSA individuals. The current findings provide enhanced support for the notion that eye contact avoidance is an important feature of social anxiety. PMID- 26677750 TI - Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment. AB - To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species. PMID- 26677751 TI - Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice. AB - Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases. PMID- 26677752 TI - LC-MS-Guided Isolation of Penicilfuranone A: A New Antifibrotic Furancarboxylic Acid from the Plant Endophytic Fungus Penicillium sp. sh18. AB - Penicilfuranone A (1), a novel furancarboxylic acid, and its proposed biosynthetic precursor, gregatin A (2), were isolated from the cultures of the fungus Penicillium sp. sh18 endophytic to the stems of Isodon eriocalyx var. laxiflora guided by HPLC-MS. X-ray crystallography was applied to the structure determination of furancarboxylic acid for the first time, allowing unambiguous assignment of 1. Penicilfuranone A displays a significant antifibrotic effect in activated hepatic stellate cells via negative regulation of transforming growth factor-beta (TGF-beta)/Smad signaling. PMID- 26677754 TI - Willingness to pay for suicide prevention in Japan. AB - The present study aimed to establish willingness to pay for suicide prevention among taxpayers in Japan. We conducted an internet-based questionnaire survey using a double-bounded dichotomous choice contingent valuation, and analyzed data for 956 participants. The median willingness to pay to reduce the mortality risk from suicide by 25% was JPY 1,572 ($13.67 USD). Being married was significantly associated with willingness to pay. The willingness to pay to reduce the mortality risk from suicide may be lower than that to reduce other mortality risks such as traffic accidents. PMID- 26677755 TI - Small-scale temporal and spatial variability in the abundance of plastic pellets on sandy beaches: Methodological considerations for estimating the input of microplastics. AB - Microplastics such as pellets have been reported for many years on sandy beaches around the globe. Nevertheless, high variability is observed in their estimates and distribution patterns across the beach environment are still to be unravelled. Here, we investigate the small-scale temporal and spatial variability in the abundance of pellets in the intertidal zone of a sandy beach and evaluate factors that can increase the variability in data sets. The abundance of pellets was estimated during twelve consecutive tidal cycles, identifying the position of the high tide between cycles and sampling drift-lines across the intertidal zone. We demonstrate that beach dynamic processes such as the overlap of strandlines and artefacts of the methods can increase the small-scale variability. The results obtained are discussed in terms of the methodological considerations needed to understand the distribution of pellets in the beach environment, with special implications for studies focused on patterns of input. PMID- 26677753 TI - Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis. AB - Ras homolog (Rho) family small GTPases are critical regulators of actin cytoskeletal organization, cell motility, proliferation, and survival. Surprisingly, the large majority of the studies underlying our knowledge of Rho protein function have been carried out in cultured cells, and it is only recently that researchers have begun to assess Rho GTPase regulation and function in vivo. The purpose of this review is to evaluate our current knowledge of Rho GTPase function in mouse mammary gland development, tumorigenesis and metastasis. Although our knowledge is still incomplete, these studies are already uncovering important themes as to the physiological roles of Rho GTPase signaling in normal mammary gland development and function. Essential contributions of Rho proteins to breast cancer initiation, tumor progression, and metastatic dissemination have also been identified. PMID- 26677756 TI - Effectiveness of Using Cellular Phones to Transmit Real-Time Shelter Morbidity Surveillance Data After Hurricane Sandy, New Jersey, October to November, 2012. AB - Timely morbidity surveillance of sheltered populations is crucial for identifying and addressing their immediate needs, and accurate surveillance allows us to better prepare for future disasters. However, disasters often create travel and communication challenges that complicate the collection and transmission of surveillance data. We describe a surveillance project conducted in New Jersey shelters after Hurricane Sandy, which occurred in November 2012, that successfully used cellular phones for remote real-time reporting. This project demonstrated that, when supported with just-in-time morbidity surveillance training, cellular phone reporting was a successful, sustainable, and less labor intensive methodology than in-person shelter visits to capture morbidity data from multiple locations and opened a two-way communication channel with shelters. (Disaster Med Public Health Preparedness. 2015;10:525-528). PMID- 26677757 TI - Is the brain reward system a mechanism of the association of sleep and pain? PMID- 26677758 TI - In vivo nonlinear imaging of corneal structures with special focus on BALB/c and streptozotocin-diabetic Thy1-YFP mice. AB - Two-photon microscopy (TPM) allows high contrast imaging at a subcellular resolution scale. In this work, the microscopy technique was applied to visualize corneal structures in two mouse models (BALB/c and B6.Cg-Tg(Thy1-YFP)16Jrs/J) in vivo. In particular, the transgenic Thy1-YFP mice expressing the yellow fluorescent protein (YFP) in all motor and sensory neurons had been used for investigating the nerve fiber density in healthy and streptozotocin-diabetic mice. This model is clinically relevant since patients suffering from diabetes mellitus have a high risk to develop small fiber neuropathy. Nonlinear laser scanning microscopy displayed a reduction of nerve fiber density in streptozotocin-diabetic versus healthy mice and confirmed data obtained by confocal laser scanning microscopy (CLSM). In recent years, corneal CLSM was proved to be an appropriate non-invasive tool for an early diagnosis of diabetic neuropathy. Nevertheless, validation of the CLSM method for the clinical routine is currently a matter of investigation and requires confirmation by further studies and complementary techniques. Thus, the present study provides further evidence of corneal confocal microscopy as a promising technique for non-invasive detection of diabetic neuropathy. Information derived from these experiments may become clinically relevant and help to develop new drugs for treatment of diabetic neuropathy. PMID- 26677759 TI - How can we identify patients with asthma-COPD overlap syndrome in clinical practice? PMID- 26677760 TI - Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells. AB - Tumors harbor a population of cancer stem cells (CSCs) which can drive tumor progression and therapeutical resistance. Nature killer (NK) cells are best known for their ability to directly recognize and kill malignant cells. However, the susceptibility of cancer stem cells to NK cells is not fully understood. Here we demonstrated that human CD44+CD24- breast CSCs were shown enhanced sensitivity to IL-2 and IL-15 activated NK cells. CD44+CD24- CSCs expressed higher levels of NKG2D ligands ULBP1, ULBP2 and MICA. Blockade assay showed that the sensitivity of CSCs to NK cells-mediated lysis was mainly dependent on NKG2D. Furthermore, redox oxygen species (ROS)-low tumor cells were more sensitive to NK cells. The presence of antioxidant enzymes inhibitor L-S,R-buthionine sulfoximine or H2O2 retarded the cytotoxicity of NK cells to CD44+CD24- CSCs. In addition, NK cells could readily target CD133+ colonal CSCs. Our findings provide novel targets for NK cells-based immunotherapy and are of great importance for translational medicine. PMID- 26677761 TI - Mycobacterium tuberculosis H37Rv infected THP-1 cells induce epithelial mesenchymal transition (EMT) in lung adenocarcinoma epithelial cell line (A549). AB - Chronic infections of Mycobacterium tuberculosis (MTB) cause oxidative stress, TLR activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. Epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. In present study, we have shown for the first time that MTB infection in human monocytic cell line (THP-1) enhances invasion and induces EMT characteristics in lung adenocarcinoma cell line (A549) during co-culture. After co-culture with MTB infected THP-1 cells A549 cells exhibited morphological and molecular signatures of EMT. During co-culture, expression of inflammatory cytokines like TNF-alpha, IL-1beta and IL 6 was enhanced in the microenvironment of A549 cells in comparison to single culture of A549 cells. Using pharmacological inhibitors of JNK (SP-600125) and p38 MAPK (SB-203580), we demonstrated the involvement of JNK and p38 MAPK in MTB induced EMT induction in A549 cells. To the best of our knowledge this is the first report demonstrating the role of MTB infection in induction of metastasis associated EMT in lung cancer. PMID- 26677762 TI - Pharmacological rescue of mutant CFTR protein improves the viscoelastic properties of CF mucus. AB - BACKGROUND: In CF patients, the defective ion transport causes a simultaneous reduction of fluid, Cl(-) and HCO3(-) secretion. We aimed to demonstrate that the resulting altered properties of mucus can be recovered using lumacaftor, a CFTR corrector. METHODS: The micro-rheology of non-CF and CF mucus was analysed using Multiple Particle Tracking. RESULTS: The diffusion coefficient of nano-beads imbedded in mucus from CF human bronchial epithelium was lower than in non-CF mucus, and the elastic and viscous moduli were higher. We found that 25% correction of F508del-CFTR mutation with lumacaftor was enough to improve significantly CF mucus properties. Surprisingly, also incubation with amiloride, a compound that reduces fluid absorption but might not change the secretion of HCO3(-) towards the airway surface fluid, improved CF mucus properties. CONCLUSION: CF mucus properties can be recovered by either improving the hydration of the airways or recovering Cl(-) and HCO3(-) secretion across the mutated protein treated with a corrector compound. PMID- 26677763 TI - Telomerase activity and its association with psychological stress, mental disorders, lifestyle factors and interventions: A systematic review. AB - OBJECTIVE: To summarise and discuss the association between telomerase activity and psychological stress, mental disorders and lifestyle factors. METHOD: A systematic review was carried out to identify prospective or retrospective studies and interventions published up to June 2015 that reported associations between telomerase activity and psychological stress, mental disorders and lifestyle factors. Electronic data bases of PubMed, ProQuest, CINAHL and Google Scholar were searched. RESULTS: Twenty six studies on humans measured telomerase activity in peripheral blood mononuclear cells (PBMCs) or leukocytes and examined its association with psychological stress, mental disorders and lifestyle factors. Of those studies, three reported significantly decreased telomerase activity in individuals under chronic psychological stress. Interestingly, one of the three studies found that acute laboratory psychological stress significantly increased telomerase activity. Nine studies reported mixed results on association between mental disorders and telomerase activity. Of the nine studies, five reported that major depressive disorder (MDD) was associated with significantly increased telomerase activity. In thirteen out of fourteen studies on lifestyle factors, it was reported that physical exercise, diet micronutrient supplementation, mindfulness meditation, Qigong practice or yoga mediation resulted in increase in telomerase activity. In addition, two studies on animal models showed that depression-like behaviour was associated with decreased hippocampus telomerase activity. Five animal studies showed that physical exercise increased telomerase activity by cell-type-specific and genotype specific manners. CONCLUSION: Although multi-facet results were reported on the association between telomerase activity and psychological stress, mental disorders and lifestyle factors, there were some consistent findings in humans such as (1) decreased telomerase activity in individuals under chronic stress, (2) increased telomerase activity in individuals with MDD, and (3) increased telomerase activity in individuals under lifestyle interventions. Animal studies showed that physical exercise increased telomerase activity in specific cell types. However, the exact mechanisms for the changes in telomerase activity have not been elucidated. We propose conglomerate models connecting chronic psychological stress, depression, mediation and physical exercise to telomerase activation. Several areas for future research are suggested. PMID- 26677764 TI - Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance. AB - Girls and women with classical congenital adrenal hyperplasia (CAH) experience elevated androgens prenatally and show increased male-typical development for certain behaviors. Further, individuals with CAH receive glucocorticoid (GC) treatment postnatally, and this GC treatment could have negative cognitive consequences. We investigated two alternative hypotheses, that: (a) early androgen exposure in females with CAH masculinizes (improves) spatial perception and quantitative abilities at which males typically outperform females, or (b) CAH is associated with performance decrements in these domains, perhaps due to reduced short-term-memory (STM). Adolescent and adult individuals with CAH (40 female and 29 male) were compared with relative controls (29 female and 30 male) on spatial perception and quantitative abilities as well as on Digit Span (DS) to assess STM and on Vocabulary to assess general intelligence. Females with CAH did not perform better (more male-typical) on spatial perception or quantitative abilities than control females, failing to support the hypothesis of cognitive masculinization. Rather, in the sample as a whole individuals with CAH scored lower on spatial perception (p <= .009), a quantitative composite (p <= .036), and DS (p <= .001), despite no differences in general intelligence. Separate analyses of adolescent and adult participants suggested the spatial and quantitative effects might be present only in adult patients with CAH; however, reduced DS performance was found in patients with CAH regardless of age group. Separate regression analyses showed that DS predicted both spatial perception and quantitative performance (both p <= .001), when age, sex, and diagnosis status were controlled. Thus, reduced STM in CAH patients versus controls may have more general cognitive consequences, potentially reducing spatial perception and quantitative skills. Although hyponatremia or other aspects of salt-wasting crises or additional hormone abnormalities cannot be ruled out as potential contributors, elevated GCs appear to be the most likely contributor to reductions in STM. Additional efforts to monitor GC administration protocols may help achieve optimal cognitive outcomes. Educational intervention for individuals with CAH might also be useful. PMID- 26677765 TI - Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation. AB - The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs). Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways. PMID- 26677767 TI - Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice. AB - Pluripotent human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose responsive human C-peptide secretion by 19-21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature beta cell markers compared with mice. Moreover, ECM related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation. PMID- 26677766 TI - Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid. AB - Prenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running. PMID- 26677768 TI - Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line. AB - A spontaneously reverted iPSC line was identified from an A-T subject with heterozygous ATM truncation mutations. The reverted iPSC line expressed ATM protein and was capable of radiation-induced phosphorylation of CHK2 and H2A.X. Genome-wide SNP analysis confirmed a match to source T cells and also to a distinct, non-reverted iPSC line from the same subject. Rearranged T cell receptor sequences predict that the iPSC culture originated as several independently reprogrammed cells that resolved into a single major clone, suggesting that gene correction likely occurred early in the reprogramming process. Gene expression analysis comparing ATM(-/-) iPSC lines to unrelated ATM(+/-) cells identifies a large number of differences, but comparing only the isogenic pair of A-T iPSC lines reveals that the primary pathway affected by loss of ATM is a diminished expression of p53-related mRNAs. Gene reversion in culture, although likely a rare event, provided a novel, reverted cell line for studying ATM function. PMID- 26677769 TI - FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self Renewal. AB - Precise self-renewal of the germ cell lineage is fundamental to fertility and reproductive success. The early precursors for the germ lineage, primordial germ cells (PGCs), survive and proliferate in several embryonic locations during their migration to the embryonic gonad. By elucidating the active signaling pathways in migratory PGCs in vivo, we were able to create culture conditions that recapitulate this embryonic germ cell environment. In defined medium conditions without feeder cells, the growth factors FGF2, insulin, and Activin A, signaling through their cognate-signaling pathways, were sufficient for self-renewal of germline-competent PGCs. Forced expression of constitutively active MEK1, AKT, and SMAD3 proteins could replace their respective upstream growth factors. Unexpectedly, we found that BMP4 could replace Activin A in non-clonal growth conditions. These defined medium conditions identify the key molecular pathways required for PGC self-renewal and will facilitate efforts in biobanking of chicken genetic resources and genome editing. PMID- 26677770 TI - Exploring the variation in implementation of a COPD disease management programme and its impact on health outcomes: a post hoc analysis of the RECODE cluster randomised trial. AB - This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes. Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC). Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation. Multilevel models were used to investigate the association between variation in implementation and change in outcomes. The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely. Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the high starting level of COPD care, the small size of the COPD population per team, the mild COPD population, practicalities of the information and communication technology (ICT) system, and hurdles in reimbursement. Level of implementation as measured with our own scale and the ACIC was not associated with health outcomes. A higher level of implementation measured with the PACIC was positively associated with improved self-management capabilities, but this association was not found for other outcomes. There was a wide variety in the implementation of RECODE, associated with barriers at individual, social, organisational and societal level. There was little association between extent of implementation and health outcomes. PMID- 26677771 TI - Improvement of liver function tests by antidiabetic agents: The need for multidirectional analysis. PMID- 26677773 TI - High-density carrier-accumulated and electrically stable oxide thin-film transistors from ion-gel gate dielectric. AB - The use of indium-gallium-zinc oxide (IGZO) has paved the way for high-resolution uniform displays or integrated circuits with transparent and flexible devices. However, achieving highly reliable devices that use IGZO for low-temperature processes remains a technological challenge. We propose the use of IGZO thin-film transistors (TFTs) with an ionic-liquid gate dielectric in order to achieve high density carrier-accumulated IGZO TFTs with high reliability, and we discuss a distinctive mechanism for the degradation of this organic-inorganic hybrid device under long-term electrical stress. Our results demonstrated that an ionic liquid or gel gate dielectric provides highly reliable and low-voltage operation with IGZO TFTs. Furthermore, high-density carrier accumulation helps improve the TFT characteristics and reliability, and it is highly relevant to the electronic phase control of oxide materials and the degradation mechanism for organic inorganic hybrid devices. PMID- 26677772 TI - Indicators of iron status are correlated with adiponectin expression in adipose tissue of patients with morbid obesity. AB - AIM: The aim of this study was to assess interactions between glucose and iron homoeostasis in the adipose tissue (AT) of obese subjects. METHODS: A total of 46 obese patients eligible for bariatric surgery were recruited into the study. Anthropometric and biochemical characteristics were assessed, and biopsies of subcutaneous (SCAT) and visceral adipose tissue (VAT) performed. The mRNA levels of genes involved in iron and glucose homoeostasis were measured in their AT and compared with a pool of control samples. RESULTS: Gene expression of hepcidin (HAMP) was significantly increased in the SCAT and VAT of obese patients, while transferrin receptor (TFRC) expression was reduced, compared with non-obese controls, suggesting a higher iron load in obese patients. Also, mRNA levels of adiponectin (ADIPOQ) were decreased in both SCAT and VAT in obese patients, and correlated negatively with hepcidin expression, while adiponectin expression was positively correlated with TFRC expression in both SCAT and VAT. Interestingly, TFRC expression in VAT correlated negatively with several metabolic parameters, such as fasting blood glucose and LDL cholesterol. CONCLUSION: Iron content appears to be increased in the SCAT and VAT of obese patients, and negatively correlated with adiponectin expression, which could be contributing to insulin resistance and the metabolic complications of obesity. PMID- 26677775 TI - [How we, as neurologists, write]. PMID- 26677774 TI - A theoretical investigation of DNA dynamics and desolvation kinetics for zinc finger proteinZif268. AB - BACKGROUND: Transcription factors, regulating the expression inventory of a cell, interact with its respective DNA subjugated by a specific recognition pattern, which if well exploited may ensure targeted genome engineering. The mostly widely studied transcription factors are zinc finger proteins that bind to its target DNA via direct and indirect recognition levels at the interaction interface. Exploiting the binding specificity and affinity of the interaction between the zinc fingers and the respective DNA can help in generating engineered zinc fingers for therapeutic applications. Experimental evidences lucidly substantiate the effect of indirect interaction like DNA deformation and desolvation kinetics, in empowering ZFPs to accomplish partial sequence specificity functioning around structural properties of DNA. Exploring the structure-function relationships of the existing zinc finger-DNA complexes at the indirect recognition level can aid in predicting the probable zinc fingers that could bind to any target DNA. Deformation energy, which defines the energy required to bend DNA from its native shape to its shape when bound to the ZFP, is an effect of indirect recognition mechanism. Water is treated as a co-reactant for unfurling the affinity studies in ZFP-DNA binding equilibria that takes into account the unavoidable change in hydration that occurs when these two solvated surfaces come into contact. RESULTS: Aspects like desolvation and DNA deformation have been theoretically investigated based on simulations and free energy perturbation data revealing a consensus in correlating affinity and specificity as well as stability for ZFP DNA interactions. Greater loss of water at the interaction interface of the DNA calls for binding with higher affinity, eventually distorting the DNA to a greater extent accounted by the change in major groove width and DNA tilt, stretch and rise. CONCLUSION: Most prediction algorithms for ZFPs do not account for water loss at the interface. The above findings may significantly affect these algorithms. Further the sequence dependent deformation in the DNA upon complexation with our prototype as well as preference of bases at the 2nd and 3rd position of the repeating triplet provide an absolutely new insight about the indirect interactions undergoing a change that have not been probed yet. PMID- 26677776 TI - [Structural and functional changes of the hippocampus in patients with multiple sclerosis and their relationship with memory processes]. AB - INTRODUCTION: One of the most prevalent cognitive deficits in multiple sclerosis (MS) patients relates to (both verbal and visual) information encoding, a process related the hippocampus. AIM: To assess the relationship between information learning and long-term retention processes and hippocampal volume and functional connectivity (FC) in MS patients. SUBJECTS AND METHODS: MS patients and a control group of healthy volunteers were assessed using the brief neuro-psychological battery, which includes tests of verbal and visual memory. Gray matter volume was assessed through the voxel based morphometry technique, and a study of seed-based FC focused on the region of ??interest (hippocampus) was also conducted. RESULTS: Results revealed that, as compared to the control group, MS patients display gray matter atrophy at the left hippocampus gray matter and smaller FC between left hippocampus and brainstem, cerebellum, fusiform gyrus and superior temporal gyrus. Association analyses were performed between memory tests performance and both volumetric and FC changes. Results showed a positive correlation between gray matter hippocampal (bilateral) volume and verbal memory performance of the MS group. Further, in MS patients, a positive correlation between visual memory performance and FC between the left hippocampus and several temporal regions was also found. CONCLUSIONS: The results of the present study reveal a relationship between structural and functional changes in the hippocampus of MS patients and their performance on verbal and visual memory tests. PMID- 26677777 TI - [The Salthouse Perceptual Comparison Test: normalization and standardization for Spanish population]. AB - INTRODUCTION: The Salthouse Perceptual Comparison Test (SPCT) assesses the processing and perceptual speed. Although this test is widely used in neuropsychology, it has not normative data adapted to Spanish population. AIM: To normalize and standardize the SPCT in Spanish population taking into account the sociodemographic characteristics of our society. SUBJECTS AND METHODS: This study is part of the multisite Normacog project. Seven hundred participants from 18 to 90 years old were assessed using the SPCT. The effect of sociodemographic characteristics such as age, level of education and sex, were analyzed on the SPCT performance, and percentiles and scalar scores adjusted by age and level of education were created. RESULTS: The effect of age and level of education on the SPCT variables analyzed (correct answers and errors of the SPCT-3 and SPCT-6) was statistically significant. Age explained the higher percentage of the variance in SPCT (SPCT-3: 47%; SPCT-6: 45%). The older participants with lower level of formal education obtained worse performance in the number of correct answers and higher number of errors. CONCLUSION: The present study reports the first normative data of the SPCT for Spanish population taking into account the sociodemographic characteristics of Spain which confirm the influence of age and level of education on the performance of the SPCT. As part of the Normacog project, this study presents the administration and correction instructions. PMID- 26677779 TI - [Mirror therapy in hemiplegic patient]. AB - INTRODUCTION: Mirror therapy is a relatively new intervention, every time more used and with easy access for the rehabilitation treatment of stroke patient. The patient moves the unaffected limb in front of a mirror watching the reflection of that move as if he was moving de affected limb. AIM: To analyze the effectiveness of mirror therapy in the sensorimotor function, hemineglect and activities of daily living of stroke patients. DEVELOPMENT: We defined a strategy of bibliography search in Medline, EMBASE, PEDro y Cochrane Central Register of Controlled Trials (CENTRAL) looking for randomised controlled trials (RCT) conducted with hemiplegic patients considering mirror therapy as the main rehabilitation intervention. Seven trials met the inclusion criteria with medium high methodological quality. Most of them evaluate the mirror therapy effect on motor outcomes showing significant improvements. Three of this RCTs evaluate the effect of mirror therapy on the hemineglect with positive result. CONCLUSIONS: A combination of mirror therapy with conventional rehabilitation obtained significant improvements mainly in motor function but not that much on sensory function and functional performance. About the effect of mirror therapy on hemineglect, there are significant improvements but supported only with a few RCTs with small sample sizes producing promising but inconclusive results. PMID- 26677778 TI - [A very slow-growing exophytic hemisphere glioma: a case report]. AB - INTRODUCTION: Gliomas are characterized by a infiltrative pattern of growth, with cellular migration along the white matter fiber tracts, exophytic growth in low grade gliomas has not been described yet. A case of hemispheric glioma with slow growing and an exophytic component is presented. CASE REPORT: 55 year-old male, with motor partial seizures. MRI shows a WHO grade II oligodendroglioma infiltrating the superior frontal gyrus with exophytic extension above the precentral gyrus. Clinical and radiological follow-up was performed for 23 years. Volumetric assessment of tumor progression revealed a growth rate of 0.5 mm per year. Surgical dissection revealed that the precentral gyrus was displaced inferiorly by the tumor, and a clear subarachnoid plane separated both structures. Functional areas were not identified within the exophytic component. Postoperative neurological deficits were not observed. CONCLUSIONS: The growth rate in low-grade gliomas has been estimated between 4 and 6 mm per year. The tumor described here had a growth rate of 0.5 mm per year, far below this average. Preoperative identification of this exophytic growth pattern is of major significance for surgical planning. The exophytic tumor is amenable for a safe and complete resection as it is covered by the arachnoid and pial membranes of the cistern and the surrounding brain. PMID- 26677780 TI - [XVIII Reunion Anual de la Sociedad Iberoamericana de Enfermedad Cerebrovascular. Communications]. PMID- 26677782 TI - [Carbon monoxide and neurology]. PMID- 26677781 TI - [WEBINO syndrome associated to chronic subdural haematoma]. PMID- 26677783 TI - [Carbon monoxide and neurology. Reply]. PMID- 26677784 TI - Diagnostic accuracy of evoked potentials for functional impairment after contusive spinal cord injury in adult rats. AB - Iatrogenic spinal cord injury (SCI) is a cause of potentially debilitating post operative neurologic complications. Currently, intra-operative neurophysiological monitoring (IONM) via somatosensory evoked potentials and motor-evoked potentials is used to detect and prevent impending SCI. However, no empirically validated interventions exist to halt the progression of iatrogenic SCI once it is detected. This is in part due to the lack of a suitable translational model that mimics the circumstances surrounding iatrogenic SCI detected via IONM. Here, we evaluate a model of simulated contusive iatrogenic SCI detected via IONM in adult female Sprague-Dawley rats. We show that transient losses of somatosensory evoked potentials responses are 88.24% sensitive (95% confidence interval [CI] 63.53 98.20) and 80% specific (95% CI 51.91-95.43) for significant functional impairment following simulated iatrogenic SCI. Similarly, we show that transient losses in motor-evoked potentials responses are 70.83% sensitive (95% CI 48.91 87.33) and 100% specific (95% CI 62.91-100.00) for significant functional impairment following simulated iatrogenic SCI. These results indicate that our model is a suitable replica of the circumstances surrounding clinical iatrogenic SCI. PMID- 26677785 TI - Durable brain response with pulse-dose crizotinib and ceritinib in ALK-positive non-small cell lung cancer compared with brain radiotherapy. AB - Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event. Whole brain irradiation, the standard treatment, results in neurocognitive impairment. We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib. Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. Clinico-pathological characteristics, treatments, and outcomes were analyzed. In two patients the progression was limited to the CNS, and radiological evidence of leptomeningeal spread was present in one patient. Sequential use of crizotinib 500mg administered once daily (pulse-dose) followed by ceritinib on progression achieved control of the disease in the CNS for over 18 months and over 7 months in Patient 1 and Patient 2, respectively. This strategy provided durable CNS control after whole-brain radiotherapy failure in Patient 1, and allowed the whole-brain radiotherapy to be deferred in Patient 2. Limited CNS progression was documented in Patient 3 while he was on standard dose/pulse-dose crizotinib for 15months; durable (over 7 months) complete remission was achieved with stereotactic radiotherapy and ceritinib. Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred. PMID- 26677786 TI - Value of intraoperative neurophysiological monitoring to reduce neurological complications in patients undergoing anterior cervical spine procedures for cervical spondylotic myelopathy. AB - The primary aim of this study was to conduct a systematic review of reports of patients with cervical spondylotic myelopathy and to assess the value of intraoperative monitoring (IOM), including somatosensory evoked potentials, transcranial motor evoked potentials and electromyography, in anterior cervical procedures. A search was conducted to collect a small database of relevant papers using key words describing disorders and procedures of interest. The database was then shortlisted using selection criteria and data was extracted to identify complications as a result of anterior cervical procedures for cervical spondylotic myelopathy and outcome analysis on a continuous scale. In the 22 studies that matched the screening criteria, only two involved the use of IOM. The average sample size was 173 patients. In procedures done without IOM a mean change in Japanese Orthopaedic Association score of 3.94 points and Nurick score by 1.20 points (both less severe post-operatively) was observed. Within our sub group analysis, worsening myelopathy and/or quadriplegia was seen in 2.71% of patients for studies without IOM and 0.91% of patients for studies with IOM. Variations persist in the existing literature in the evaluation of complications associated with anterior cervical spinal procedures. Based on the review of published studies, sufficient evidence does not exist to make recommendations regarding the use of different IOM modalities to reduce neurological complications during anterior cervical procedures. However, future studies with objective measures of neurological deficits using a specific IOM modality may establish it as an effective and reliable indicator of injury during such surgeries. PMID- 26677787 TI - Metabonomic analysis of quercetin against the toxicity of chronic exposure to a mixture of four organophosphate pesticides in rat plasma. AB - 1. A metabonomics approach was performed to investigate the effect of quercetin on the toxicity of chronic exposure to a mixture of four organophosphate pesticides (OPs) at their corresponding no-observed-adverse-effect level (NOAEL). The rats were divided into six groups (n = 10/group): control, two different doses of quercetin, OPs mixture and different doses of quercetin plus OPs mixture treated groups. 2. Nine metabolites, including two quercetin metabolites and seven endogenous metabolites were identified in plasma. The intensities of metabolites significantly changed in the OP mixture-treated group compared with the control group (p < 0.01), such as lysoPE (16:0/0:0), lysoPC (17:0/0:0), lysoPC (15:0/0:0) and 4-pyridoxic acid, significantly increased; by contrast, the intensities of arachidonic acid and citric acid significantly decreased. Anomalous intensity changes in aforementioned metabolites were alleviated in the OP mixture plus 50 mg/kgcbw/d quercetin-treated group compared with the OP mixture-treated group (p < 0.05). 3. The results indicated that quercetin elicited partial protective effects against the toxicity induced by a mixture of OPs, which include regulation of lipid metabolism, improvement of tricarboxylic acid (TCA) cycle disorders, enhancement of antioxidant defence system to protect the liver. PMID- 26677788 TI - Prevention of chemotherapy-induced ovarian damage. AB - Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity. PMID- 26677789 TI - Improving family planning with the use of long-acting reversible contraception use. PMID- 26677791 TI - Risks beyond reproduction for infertile men. PMID- 26677790 TI - Fertility preservation in Turner syndrome. AB - Premature ovarian insufficiency is a relatively rare condition that can appear early in life. In a non-negligible number of cases the ovarian dysfunction results from genetic diseases. Turner syndrome (TS), the most common sex chromosome abnormality in females, is associated with an inevitable premature exhaustion of the follicular stockpile. The possible or probable infertility is a major concern for TS patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The severely reduced follicle pool even during prepubertal life represents the major limit for fertility preservation and is the root of numerous questions regarding the competence of gametes or ovarian tissue crybanked. In addition, patients suffering from TS show higher than usual rates of spontaneous abortion, fetal anomaly, and maternal morbidity and mortality, which should be considered at the time of fertility preservation and before reutilization of the cryopreserved gametes. Apart from fulfillment of the desire of becoming genetic parents, TS patients may be potential candidates for egg donation, gestational surrogacy, and adoption. The present review discusses the different options for preserving female fertility in TS and the ethical questions raised by these approaches. PMID- 26677792 TI - Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. AB - OBJECTIVE: To assess the proportion of patients satisfied with their treatment before and after a systematic change from norethindrone acetate to dienogest as the first-line progestin for symptomatic endometriosis. DESIGN: Before and after study. SETTING: Academic department. PATIENT(S): The last 90 new consecutive endometriosis patients in whom norethindrone acetate was used, and the first 90 new consecutive endometriosis patients in whom dienogest was used. INTERVENTION(S): Norethindrone acetate at the oral dose of 2.5 mg once a day until June 6, 2013, then dienogest at the oral dose of 2 mg once a day thereafter. MAIN OUTCOME MEASURE(S): Degree of satisfaction with treatment after 6 months of progestin therapy and assessment of any variations in pain symptoms, psychological status, sexual function, or health-related quality of life associated with the introduction of dienogest. RESULT(S): The proportion of satisfied plus very satisfied women after 6 months of treatment was 71% in the "before" period (norethindrone acetate) and 72% in the "after" period (dienogest). The implementation of dienogest was not associated with statistically significant ameliorations in overall pain relief, psychological status, sexual functioning, or health-related quality of life. Treatment was well tolerated by 58% of norethindrone acetate users compared with 80% of dienogest users. After dienogest implementation, the absolute risk reduction in the occurrence of any side effect was 13.9% (95% confidence interval, 0.8%-28.6%). CONCLUSION(S): Considering the large difference in the cost of the two drugs, dienogest should be suggested selectively in women who do not tolerate norethindrone acetate. PMID- 26677793 TI - Presence and characterization of pig group A and C rotaviruses in feces of Belgian diarrheic suckling piglets. AB - The importance of group A and C rotaviruses (RVA and RVC) in the pathogenesis of diarrhea in Belgian suckling pigs is poorly investigated, and it is not known which strains are circulating in the Belgian suckling pig population. Obtaining better insights in the occurrence of both viral species in the swine population is essential in order to develop accurate diagnostic, therapeutic and prophylactic strategies to protect suckling pigs against diarrhea in a durable manner. In the present study, viral loads of RVA and RVC were quantified in diarrhea samples of suckling piglets less than 2 weeks old, collected on 36 different Belgian farms. On 22 of 36 farms tested (61%), high viral loads of RVA (6.96-11.95 log10 copies/g feces) and/or RVC (5.40-11.63 log10 copies/g feces) were detected. Seventeen RVA isolates were genotyped for their outer capsid proteins VP7 and VP4. Four different G-genotypes (G3, G4, G5 and G9) for VP7 were found together with 4 different P-genotypes (P[6], P[7], P[13] and P[23]) for VP4, in 8 different G/P combinations. All characterized RVC strains belonged to genotype G6 (VP7), except for one strain possessing the G1 genotype. VP4 genes of Belgian RVC strains were genetically heterogeneous, but were classified in the genotype P5. Most rotavirus positive samples also contained Escherichia coli, whereas Clostridium perfringens infections were mainly detected in rotavirus negative samples. Results of the present study offer better insights in the occurrence of RVA and RVC infections in Belgian diarrheic suckling piglets. As a conclusion, routine diagnostic testing for both viral species in cases of diarrhea in suckling pigs is highly recommended. Furthermore, the present findings also offer valuable information for the development of new prophylactic measures against rotavirus. Finally, the relatedness between RVC strains from pigs and other host species is described, and their possible implications in interspecies transmission events are discussed. PMID- 26677794 TI - Comment on 'Building allied health workforce capacity: a strategic approach to workforce innovation'. PMID- 26677796 TI - Multipod-like silica/polystyrene clusters. AB - Multipod-like clusters composed of a silica core and PS satellites are prepared according to a seeded-growth emulsion polymerization of styrene in the presence of size-monodisperse silica particles previously surface-modified with methacryloxymethyltriethoxysilane. Tuning the diameter and concentration of the silica seeds affords homogeneous batches of tetrapods, hexapods, octopods, nonapods and dodecapods with morphology yields as high as 80%. Three-dimensional reconstructions by cryo-electron tomography are presented on large fields for the first time to show the high symmetry and regularity of the clusters demonstrating the good control of the synthesis process. These synthesis experiments are visited again digitally, in order to successfully refine an original simulation model and better understand the correlation between the history of the cluster growth and the final composition of the cluster mixture. Finally, using the model as a predictive tool and varying the extra experimental conditions, e.g. the composition of the surfactant mixture and the styrene concentration, result in trapping other cluster morphologies, such as tripods. PMID- 26677795 TI - Characterization and Comparative Analysis of the Milk Transcriptome in Two Dairy Sheep Breeds using RNA Sequencing. AB - This study presents a dynamic characterization of the sheep milk transcriptome aiming at achieving a better understanding of the sheep lactating mammary gland. Transcriptome sequencing (RNA-seq) was performed on total RNA extracted from milk somatic cells from ewes on days 10, 50, 120 and 150 after lambing. The experiment was performed in Spanish Churra and Assaf breeds, which differ in their milk production traits. Nearly 67% of the annotated genes in the reference genome (Oar_v3.1) were expressed in ovine milk somatic cells. For the two breeds and across the four lactation stages studied, the most highly expressed genes encoded caseins and whey proteins. We detected 573 differentially expressed genes (DEGs) across lactation points, with the largest differences being found, between day 10 and day 150. Upregulated GO terms at late lactation stages were linked mainly to developmental processes linked to extracellular matrix remodeling. A total of 256 annotated DEGs were detected in the Assaf and Churra comparison. Some genes selectively upregulated in the Churra breed grouped under the endopeptidase and channel activity GO terms. These genes could be related to the higher cheese yield of this breed. Overall, this study provides the first integrated overview on sheep milk gene expression. PMID- 26677797 TI - Behavior, preferences, and willingness to pay for measures aimed at preventing pollution by pharmaceuticals and personal care products in China. AB - The release of pharmaceuticals and personal care products (PPCPs) into the environment has been held up as a potential threat to ecosystem and human health. Using a custom-designed survey of residents living in Xiamen, China, this paper examines individuals' disposal practices, awareness of the environmental impact of PPCPs, and willingness to pay for measures aimed at reducing the likelihood of PPCPs being released into the environment. The vast majority of respondents report that they dispose of PPCPs through the thrash. The results of a contingent valuation experiment suggest a substantial willingness to pay (WTP) for policy measures aimed at reducing PPCP pollution. Income as well as subjective perceptions relating to overall financial health, expenditure on PPCPs, and overall concern with environmental issues emerged as significant predictors of respondents' WTP. Our results should be of interest to policymakers looking for ways to mitigate the introduction of PPCPs in the environment. Integr Environ Assess Manag 2016;12:793-800. (c) 2015 SETAC. PMID- 26677798 TI - Prescription Writing in Small Groups as a Clinical Pharmacology Educational Intervention: Perceptions of Preclerkship Medical Students. AB - Medical students do not perform well in writing prescriptions, and the 3 variables-learner, teacher, and instructional method-are held responsible to various degrees. The objective of this clinical pharmacology educational intervention was to improve medical students' perceptions, motivation, and participation in prescription-writing sessions. The study participants were second-year medical students of the College of Medicine and Medical Sciences of the Arabian Gulf University, Bahrain. Two prescription-writing sessions were conducted using clinical case scenarios based on problems the students had studied as part of the problem-based learning curriculum. At the end of the respiratory system subunit, the training was conducted in small groups, each facilitated by a tutor. At the end of the cardiovascular system subunit, the training was conducted in a traditional large-group classroom setting. Data were collected with the help of a questionnaire at the end of each session and a focus group discussion. A majority of the students (95.3% +/- 2.4%) perceived the small group method better for teaching and learning of all aspects of prescription writing: analyzing the clinical case scenario, applying clinical pharmacology knowledge for therapeutic reasoning, using a formulary for searching relevant prescribing information, and in writing a complete prescription. Students also endorsed the small-group method for better interaction among themselves and with the tutor and for the ease of asking questions and clarifying doubts. In view of the principles of adult learning, where motivation and interaction are important, teaching and learning prescription writing in small groups deserve a serious consideration in medical curricula. PMID- 26677799 TI - Structural and magnetic modulations of copper(II) azido complexes: unexpected in situ reactions of mono-N-donor pyridine-based co-ligands. AB - Low-temperature hydrothermal reactions of copper salts with NaN3 and structurally related pyridine-based ligands, 1-(4-pyridyl)pyridinium, 3-chloromethylpyridine, 4-benzylpyridine, and quinoline (L(4)), respectively, led to the formation of four new magnetic complexes, [Cu3(L(1))2(N3)6]n (), [Cu3(L(2))2(N3)6]n (), [Cu(L(3))2(N3)2] (), and [Cu(L(4))(N3)2]n (). In these complexes, L(1), L(2), and L(3) are pyridine, 3-azidomethylpyridine, and 4-benzoylpyridine, being generated in situ by the decomposition, azido substitution, and oxidation reaction of the 1 (4-pyridyl)pyridinium, 3-chloromethylpyridine, and 4-benzylpyridine, respectively. and have similar structures being composed of double end-on azido bridging planar [Cu3(L)2(N3)6] trinuclear units, which are further linked into a two-dimensional layer by the end-to-end azido bridges of themselves, along with their weak end-on coordination. It is interesting that the only slight differences of geometrical parameters in and have led to distinct magnetic interactions between the trinuclear units, where the former is antiferromagnetic but the latter is ferromagnetic, whereas has a mono-nuclear core structure, which is further extended to a one-dimensional (1D) chain by weakly coordinated end-on azido bridges. consists of unique 1D chains with double end-on azido bridge bonding distorted five-coordinated Cu(ii) centers, and exhibits ferromagnetic intrachain interactions. In the structures of these complexes there also exist weak inter-layer or inter-chain hydrogen bonds, which should also be responsible for some magnetic behavior at low temperature. In addition, primary structural and magnetic comparisons and discussions have also been performed by combining other reported azido-Cu(ii) systems with related pyridyl-based co-ligands. These results show that the selection of synthesis conditions and slight decoration of co-ligands (or geometric differences of them) have important influences on the structures and magnetic properties of resulting metal azido complexes. PMID- 26677800 TI - Highly CO2 sensitive extruded fluorescent plastic indicator film based on HPTS. AB - Highly-sensitive optical fluorescent extruded plastic films are reported for the detection of gaseous and dissolved CO2. The pH-sensitive fluorescent dye used is 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS, PTS(-)) coated on the surface of hydrophilic fumed silica and the base is tetrabutylammonium hydroxide (TBAH). The above components are used to create an HPTS pigment (i.e. HPTS/SiO2/TBAH) with a high CO2 sensitivity (%CO2 (S = 1/2) = 0.16%) and fast 50% response (t50?) = 2 s and recovery (t50?) = 5 s times. Highly CO2-sensitive plastic films are then fabricated, via the extrusion of the HPTS pigment powder in low-density polyethylene (LDPE). As with the HPTS-pigment, the luminescence intensity (at 515 nm) and absorbance (at 475 nm) of the HPTS plastic film decreases as the %CO2 in the ambient gas phase increases. The HPTS plastic film exhibits a high CO2 sensitivity, %CO2 (S = 1/2), of 0.29%, but a response time <2 min and recovery time <40 min, which is slower than that of the HPTS pigment. The HPTS plastic film is very stable under ambient conditions, (with a shelf life >six month when stored in the dark but under otherwise ambient conditions). Moreover, the HPTS-LDPE film is stable in water, salt solution and even in acid (pH = 2), and in each of these media it can be used to detect dissolved CO2. PMID- 26677801 TI - Synthesis of 1-Naphthol by a Natural Peroxygenase Engineered by Directed Evolution. AB - There is an increasing interest in enzymes that catalyze the hydroxylation of naphthalene under mild conditions and with minimal requirements. To address this challenge, an extracellular fungal aromatic peroxygenase with mono(per)oxygenase activity was engineered to convert naphthalene selectively into 1-naphthol. Mutant libraries constructed by random mutagenesis and DNA recombination were screened for peroxygenase activity on naphthalene together with quenching of the undesired peroxidative activity on 1-naphthol (one-electron oxidation). The resulting double mutant (G241D-R257K) obtained from this process was characterized biochemically and computationally. The conformational changes produced by directed evolution improved the substrate's catalytic position. Powered exclusively by catalytic concentrations of H2 O2 , this soluble and stable biocatalyst has a total turnover number of 50 000, with high regioselectivity (97 %) and reduced peroxidative activity. PMID- 26677802 TI - Optineurin deficiency in mice is associated with increased sensitivity to Salmonella but does not affect proinflammatory NF-kappaB signaling. AB - Optineurin (OPTN) is an evolutionary conserved and ubiquitously expressed ubiquitin-binding protein that has been implicated in glaucoma, Paget bone disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. From in vitro studies, OPTN was shown to suppress TNF-induced NF-kappaB signaling and virus-induced IRF signaling, and was identified as an autophagy receptor required for the clearance of cytosolic Salmonella upon infection. To assess the in vivo functions of OPTN in inflammation and infection, we generated OPTN deficient mice. OPTN knockout mice are born with normal Mendelian distribution and develop normally without any signs of spontaneous organ abnormality or inflammation. However, no differences in NF-kappaB activation could be observed in OPTN knockout mice or fibroblasts derived from these mice upon TNF or LPS treatment. Primary bone marrow-derived macrophages from OPTN-deficient mice had slightly impaired IRF signaling and reduced IFN type I production in response to LPS or poly(I,C). Finally, OPTN-deficient mice were more susceptible to infection with Salmonella, confirming in vivo the importance of OPTN in bacterial clearance. PMID- 26677803 TI - Increasing awareness of sex differences in airway diseases. AB - There is growing epidemiologic data demonstrating sex differences with respect to prevalence and progression of airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and non-CF-related bronchiectasis. In asthma, for example, young boys have increased exacerbations and higher morbidity than girls which distinctly reverses after adolescence and into adulthood. In COPD, a disease that was historically considered an illness of men, the number of women dying per year is now greater than in men. Finally, women with CF-related bronchiectasis have a decreased median life expectancy relative to men and a higher risk of respiratory infections despite equal prevalence of the disease. A number of studies now exist demonstrating mechanisms behind these sex differences, including influences of genetic predisposition, sex hormones and comorbidities. The notable sex disparity has potential diagnostic, therapeutic and prognostic implications and for the practicing respiratory or general physician, a familiarity with these distinctions may augment effective management of patients with airway diseases. This review seeks to concisely summarize the data regarding gender-based differences in airway diseases, outline the current understanding of contributing factors and discuss therapeutic implications for clinicians. PMID- 26677804 TI - Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes. AB - Differentiated podocytes, a type of renal glomerular cells, require substantial levels of energy to maintain glomerular physiology. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. This study evaluated the roles of mitochondria and glycolysis in differentiated and differentiating podocytes. Mitochondria in differentiated podocytes are located in the central part of cell body while blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, decreased the cell migratory ability and induced the apoptosis. Consistently, the local ATP production in lamellipodia was predominantly regulated by glycolysis. In turn, synaptopodin expression was ameliorated by blocking either mitochondrial respiration or glycolysis. Similar to differentiated podocytes, the differentiating podocytes utilized the glycolysis for regulating apoptosis and lamellipodia formation while synaptopodin expression was likely involved in both mitochondrial OXPHOS and glycolysis. Finally, adult mouse podocytes have most of mitochondria predominantly in the center of the cytosol whereas phosphofructokinase, a rate limiting enzyme for glycolysis, was expressed in foot processes. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes. PMID- 26677805 TI - Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection. AB - Nrf2-small Maf (sMaf) heterodimer is essential for the inducible expression of cytoprotective genes upon exposure to oxidative and xenobiotic stresses. While the Nrf2-sMaf heterodimer recognizes DNA sequences referred to as the antioxidant/electrophile responsive element (ARE/EpRE), we here define these DNA sequences collectively as CNC-sMaf binding element (CsMBE). In contrast, large and small Maf proteins are able to form homodimers that recognize the Maf recognition element (MARE). CsMBE and MARE share a conserved core sequence but they differ in the 5'-adjacent nucleotide neighboring the core. Because of the high similarity between the CsMBE and MARE sequences, it has been unclear how many target binding sites and target genes are shared by the Nrf2-sMaf heterodimers and Maf homodimers. To address this issue, we introduced a substitution mutation of alanine to tyrosine at position 502 in Nrf2, which rendered the DNA-binding domain structure of Nrf2 similar to Maf, and generated knock-in mice expressing the Nrf2(A502Y) mutant. Our chromatin immunoprecipitation-sequencing analyses showed that binding sites of Nrf2(A502Y) sMaf were dramatically changed from CsMBE to MARE in vivo. Intriguingly, however, one-quarter of the Nrf2(A502Y)-sMaf binding sites also bound Nrf2-sMaf commonly and vice versa. RNA-sequencing analyses revealed that Nrf2(A502Y)-sMaf failed to induce expression of major cytoprotective genes upon stress stimulation, which increased the sensitivity of Nrf2(A502Y) mutant mice to acute acetaminophen toxicity. These results demonstrate that the unique cistrome defined as CsMBE is strictly required for the Nrf2-sMaf heterodimer function in cytoprotection and that the roles played by CsMBE differ sharply from those of MARE. PMID- 26677806 TI - Predicting future lung function decline in cystic fibrosis patients: Statistical methods and clinical connections. PMID- 26677807 TI - Bioconversion of sodium dodecyl sulphate to rhamnolipids by transformed Escherichia coli DH5alpha cells-a novel strategy for rhamnolipid synthesis. AB - AIMS: Biological synthesis of rhamnolipids from SDS by Pseudomonas aeruginosa S15 is found to be a cost effective mode of rhamnolipid synthesis. This study aimed to attempt rhamnolipid synthesis by transformant Escherichia coli DH5alpha cells. METHODS AND RESULTS: Molecular analysis by curing experiments revealed that the properties of SDS based rhamnolipid synthesis were plasmid borne. Transformation of 10 kb plasmid to E. coli DH5alpha cells conferred rhamnolipid synthetic ability to transformant. Various genetic elements involved in SDS based rhamnolipid synthesis were analyzed using PCR based and restriction digestion based approaches. PCR amplification using primers specific for sdsA gene encoding alkylsulfatases yielded two significant amplicons viz, 1.2 kb fragment and 422 bp fragment, coding for putative dehydratase and ABC transporter respectively. Amplicon of sdsB gene lacked ability of SDS degradation and rhamnolipid synthesis. Rhamnolipid biosynthesis by transformant E. coli DH5alpha containing the whole of the 10 kb plasmid, was optimized to yield of 3.38 g l(-1) in 5 days of incubation. CONCLUSIONS: Plasmid encoded rhamnolipid synthesis from recombinant E. coli cells is novel and could serve as yet another promising approach among various steps adopted for safe and effective rhamnolipid synthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: SDS based rhamnolipid synthesis by S15 attained a high substrate (SDS) to product (Rhamnolipid) conversion ratio. However, the use of Pseudomonas strains is always discouraged as they are opportunistic pathogens and could sometimes turn infectious. Thus, transformation of genetic elements coding SDS based rhamnolipid synthesis to nonpathogenic strains could be promising. PMID- 26677808 TI - Stability of Trans-Resveratrol Encapsulated in a Protein Matrix Produced Using Spray Drying to UV Light Stress and Simulated Gastro-Intestinal Digestion. AB - Trans-resveratrol has demonstrated the potential to provide both therapeutic and preventive activities against chronic diseases such as heart disease and cancer. The incorporation of trans-resveratrol into food products would allow for broader access of this bioactive compound to a larger population. However, this strategy is limited by instability of trans-resveratrol under environmental conditions and within the digestive system leading to isomerization of trans-resveratrol (bioactive form) to cis-resveratrol (bio-inactive form). Studies in the stabilization of trans-resveratrol into protein microparticles are presented. Trans-resveratrol was encapsulated using whey protein concentrate (WPC) or sodium caseinate (SC), with or without anhydrous milk fat (AMF). Binding of resveratrol and aromatic residues in protein was estimated utilizing the Stern-Volmer equation and the number of tryptophan residues. The stability of encapsulated resveratrol was evaluated after exposure to ultraviolet A (UVA) light and 3-stage in vitro digestion. After UVA light exposure, SC-based microcapsules maintained a higher trans:cis resveratrol ratio (0.63, P < 0.05) than WPC-based microcapsules (0.43) and unencapsulated resveratrol (0.49). In addition, encapsulation of resveratrol in both protein microparticles led to an increased digestive stability and bioaccessibility in comparison to unencapsulated resveratrol (47% and 23%, respectively, P < 0.05). SC-based microcapsules provided a higher digestive stability and bioaccessibility (86% and 81%; P < 0.05) compared to WPC based microcapsules (71% and 68%). The addition of AMF to the microcapsules did not significantly change the in vitro digestion values. In conclusion, SC-based microencapsulation increased the stability of trans-resveratrol to UVA light exposure and simulated digestion conditions. This encapsulation-system-approach can be extended to other labile, bioactive polyphenols. PMID- 26677809 TI - Assessment of the Hong Kong Liver Cancer Staging System in Europe. AB - BACKGROUND & AIMS: European and American guidelines have endorsed the Barcelona Clinic Liver Cancer (BCLC) staging system. The aim of this study was to assess the performance of the recently developed Hong Kong Liver Cancer (HKLC) classification as a staging system for hepatocellular carcinoma (HCC) in Europe. METHODS: We used a pooled set of 1693 HCC patients combining three prospective European cohorts. Discrimination ability between the nine substages and five stages of the HKLC classification system was assessed. To evaluate the predictive power of the HKLC and BCLC staging systems on overall survival, Nagelkerke pseudo R2, Bayesian Information Criterion and Harrell's concordance index were calculated. The number of patients who would benefit from a curative therapy was assessed for both staging systems. RESULTS: The HKLC classification in nine substages shows suboptimal discrimination between the staging groups. The classification in five stages shows better discrimination between groups. However, the BCLC classification performs better than the HKLC classification in the ability to predict overall survival (OS). The HKLC treatment algorithm tags significantly more patients to curative therapy than the BCLC. CONCLUSIONS: The BCLC staging system performs better for European patients than the HKLC staging system in predicting OS. Twice more patients are eligible for a curative therapy with the HKLC algorithm; whether this translates in survival benefit remains to be investigated. PMID- 26677816 TI - Using CRISPR/Cas in three dimensions: towards synthetic plant genomes, transcriptomes and epigenomes. AB - It is possible to target individual sequence motives within genomes by using synthetic DNA-binding domains. This one-dimensional approach has been used successfully in plants to induce mutations or for the transcriptional regulation of single genes. When the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system was discovered, a tool became available allowing the extension of this approach from one to three dimensions and to construct at least partly synthetic entities on the genome, epigenome and transcriptome levels. The second dimension can be obtained by targeting the Cas9 protein to multiple unique genomic sites by applying multiple different single guiding (sg) RNAs, each defining a different DNA-binding site. Finally, the simultaneous use of phylogenetically different Cas9 proteins or sgRNAs that harbour different types of protein binding motives, allows for a third dimension of control. Thus, different types of enzyme activities - fused either to one type of Cas9 orthologue or to one type of RNA-binding domain specific to one type of sgRNA - can be targeted to multiple different genomic sites simultaneously. Thus, it should be possible to induce quantitatively different levels of expression of certain sets of genes and at the same time to repress other genes, redefining the nuclear transcriptome. Likewise, by the use of different types of histone modifying and/or DNA (de)methylating activities, the epigenome of plants should be reprogrammable. On our way to synthetic plant genomes, the next steps will be to use complex genome engineering approaches within or between species borders to restructure and recombine natural or artificial chromosomes. PMID- 26677817 TI - Integrative methods for analyzing big data in precision medicine. AB - We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of "Big Data" in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face. PMID- 26677818 TI - Differential protein expression in the estuarine copepod Eurytemora affinis after diuron and alkylphenol exposures. AB - Proteomics was used in the calanoid copepod Eurytemora affinis for screening of protein expression modifications induced by organic contaminants. The copepods were exposed in a continuous flow-through system for 86 h to environmentally relevant concentrations of contaminants representative of the pollution in the Seine Estuary (Haute-Normandie, France; diuron, 500 ng L(-1) ; alkylphenol mixture, 1000 ng L(-1) ). Proteome analysis of whole-body copepod extracts by 2 dimensional gel electrophoresis revealed that the contaminants induced modifications in protein expression, with the highest quantitative variations occurring after diuron exposure. Specifically, 88 and 41 proteins were differentially expressed after diuron and alkylphenol treatments, respectively. After mass spectrometry analysis, 51 (diuron exposure) and 15 (alkylphenol exposure) proteins were identified. The identified proteins were potentially related to energy metabolism, cell growth, nervous signal conductivity, excitotoxicity, oxidative stress response, and antioxidant defense. The data suggest a massive general disturbance of physiological functions of E. affinis after diuron exposure, whereas alkylphenols induced an alteration of a few targeted physiological functions. The protein expression signatures identified after contaminant exposure deserve further investigation in terms of the development of novel potential biomarkers for water quality assessment. Environ Toxicol Chem 2016;35:1860-1871. (c) 2015 SETAC. PMID- 26677820 TI - Super-resolution optical telescopes with local light diffraction shrinkage. AB - Suffering from giant size of objective lenses and infeasible manipulations of distant targets, telescopes could not seek helps from present super-resolution imaging, such as scanning near-field optical microscopy, perfect lens and stimulated emission depletion microscopy. In this paper, local light diffraction shrinkage associated with optical super-oscillatory phenomenon is proposed for real-time and optically restoring super-resolution imaging information in a telescope system. It is found that fine target features concealed in diffraction limited optical images of a telescope could be observed in a small local field of view, benefiting from a relayed metasurface-based super-oscillatory imaging optics in which some local Fourier components beyond the cut-off frequency of telescope could be restored. As experimental examples, a minimal resolution to 0.55 of Rayleigh criterion is obtained, and imaging complex targets and large targets by superimposing multiple local fields of views are demonstrated as well. This investigation provides an access for real-time, incoherent and super resolution telescopes without the manipulation of distant targets. More importantly, it gives counterintuitive evidence to the common knowledge that relayed optics could not deliver more imaging details than objective systems. PMID- 26677821 TI - Uterine Sarcomas in Patients Undergoing Surgery for Presumed Leiomyomas: 10 Years' Experience. AB - STUDY OBJECTIVE: To find the incidence of sarcomas in patients undergoing surgery for presumed leiomyomas. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Paul's Hospital, Centre for Advanced Laparoscopy and Infertility, Kochi, India. PATIENTS: All women who underwent total laparoscopic hysterectomy (TLH), laparoscopic myomectomy (LM), and hysteroscopic myomectomy (HM) at Paul's Hospital for presumed leiomyomas from January 1, 2004 to December 31, 2014 that were then diagnosed as sarcomas on histopathologic examination. INTERVENTIONS: TLH, LM, and HM. MEASUREMENTS AND MAIN RESULTS: A total of 2678 patients underwent TLH, LM, and HM at Paul's Hospital for presumed leiomyomas from January 1, 2004 to December 31, 2014. Five patients were diagnosed as leiomyosarcoma and 3 patients as endometrial stromal sarcoma on histopathologic examination. Women's ages ranged from 12 to 53 years. Histopathologic diagnosis of leiomyosarcoma was made in 3 patients from the TLH group and 2 patients from the myomectomy group. Two patients from the TLH group and 1 patient from the myomectomy group were diagnosed as endometrial stromal sarcoma on histopathologic examination. The incidence of uterine sarcomas (leiomyosarcoma and endometrial stromal sarcoma) in patients undergoing surgery for presumed leiomyomas was found to be .29% (1 in 335 patients) in our study. CONCLUSION: Over a period of 10 years (2004-2014), the incidence of uterine sarcomas in patients undergoing surgery for presumed leiomyomas was found to be .29% in our study. PMID- 26677822 TI - Spinal stability after resection of nerve sheath tumors. AB - BACKGROUND: The aim of this paper was to present a generalizable group of patients who have undergone resection of spinal nerve sheath tumors and attempt to identify factors that may be predictive of the need for intraoperative fusion. METHODS: We conducted a retrospective review of patients who underwent excision of spinal nerve sheath tumors performed by the senior author at the University of Miami/Jackson Memorial Medical Center. RESULTS: Out of the 48 cases reviewed in this study, a total of 7 (14.6%) underwent fusion at the same time as decompression and tumor excision. Fusion was deemed necessary in these cases for a number of different reasons, including preexisting scoliosis, cervical instability, preexisting listhesis, and tumor size and/or aggressiveness warranting more extensive bony exposure. Cervical tumors in patients with NF-1 and total facetectomy being performed were both factors found to be predictive of the decision to perform intraoperative fusion with instrumentation (P values of 0.009 and <0.001, respectively). There were seven cases in which partial facetectomies were performed without fusion, none of which later developed instability. Finally, excision of malignant peripheral nerve sheath tumors was also associated with the decision to perform fusion (P=0.008). The average length of follow-up was 2 years, 11 months (SEM 8 months). CONCLUSIONS: Most patients can undergo resection of spinal nerve sheath tumors without fusion. Patients with pre-existing deformity or instability, a history of NF-1 together with the tumor in the cervical region, malignant nerve sheath tumors, or those who undergo a total facet resection may require instrumented spinal fusion during tumor excision. We also observed that removal of one third or even half of a facet joint complex appears to be well tolerated with no instability seen on follow-up. PMID- 26677823 TI - Position statement from the Italian Society of Neurosurgery on the ARUBA Study. AB - As the conclusions of the ARUBA Study are strongly oriented towards therapeutic abstention, we think it is appropriate to express the concern of the Italian Society of Neurosurgery for the impact that this study might have on the health of patients, if not properly evaluated. The vast majority of patients (76-81%) included in the study was treated with endovascular or radiotherapy treatments, alone or in combination. Only 18 patients (19%) had surgery. It is well known that a partial treatment of arteriovenous malformations (AVMs), as is often the case with endovascular therapy, may increase the risk of bleeding. The primary endpoint (death or symptomatic stroke) in the treated group was reached in 30.7%, i.e. almost one-third of the subjects. This has no comparison in the current surgical literature. Considering permanent and transient neurological deficits along with headaches and seizures all together in the same outcome evaluation parameter may be inappropriate and misleading. The graph with all results from the ARUBA Study, which claims to be the demonstration that natural history is better that treatment, clearly shows that what is assumed to be treated has not actually been treated. If death or stroke occur a few years from treatment, it only means that the disease was not cured and patients received a partial - therefore ineffective, if not dangerous - treatment. An effective treatment, as surgery is, must have a flat follow-up curve. The ARUBA Study shows that incomplete treatment leads to negative outcome, confirming that an integrated multidisciplinary strategy has to be plotted out before starting any treatment and that a complete exclusion of the AVM must be achieved. PMID- 26677824 TI - Heat-acclimatization and pre-cooling: a further boost for endurance performance? AB - To determine if pre-cooling (PC) following heat-acclimatization (HA) can further improve self-paced endurance performance in the heat, 13 male triathletes performed two 20-km cycling time-trials (TT) at 35 degrees C, 50% relative humidity, before and after an 8-day training camp, each time with (PC) or without (control) ice vest PC. Pacing strategies, physiological and perceptual responses were assessed during each TT. PC and HA induced moderate (+10 +/- 18 W; effect size [ES] 4.4 +/- 4.6%) and very large (+28 +/- 19 W; ES 11.7 +/- 4.1%) increases in power output (PO), respectively. The overall PC effect became unclear after HA (+4 +/- 14 W; ES 1.4 +/- 3.0%). However, pacing analysis revealed that PC remained transiently beneficial post-HA, i.e., during the first half of the TT. Both HA and PC pre-HA were characterized by an enhanced PO without increased cardio-thermoregulatory or perceptual disturbances, while post-HA PC only improved thermal comfort. PC improved 20-km TT performance in unacclimatized athletes, but an 8-day HA period attenuated the magnitude of this effect. The respective converging physiological responses to HA and PC may explain the blunting of PC effectiveness. However, perceptual benefits from PC can still account for the small alterations to pacing noted post-HA. PMID- 26677827 TI - Accuracy of PARTwear Inertial Sensor and Optojump Optical Measurement System for Measuring Ground Contact Time During Running. AB - Ammann, R, Taube, W, and Wyss, T. Accuracy of PARTwear inertial sensor and Optojump optical measurement system for measuring ground contact time during running. J Strength Cond Res 30(7): 2057-2063, 2016-The aim of this study was to validate the detection of ground contact time (GCT) during running in 2 differently working systems: a small inertial measurement sensor, PARTwear (PW), worn on the shoe laces, and the optical measurement system, Optojump (OJ), placed on the track. Twelve well-trained subjects performed 12 runs each on an indoor track at speeds ranging from 3.0 to 9.0 m.s. GCT of one step per run (total 144) was simultaneously obtained by the PW, the OJ, and a high-speed video camera (HSC), whereby the latter served as reference system. The sampling rate was 1,000 Hz for all methods. Compared with the HSC, the PW and the OJ systems underestimated GCT by -1.3 +/- 6.1% and -16.5 +/- 6.7% (p-values <= 0.05), respectively. The intraclass correlation coefficients between PW and HSC and between OJ and HSC were 0.984 and 0.853 (p-values < 0.001), respectively. Despite the constant systematic underestimation of GCT, analyses indicated that PW successfully recorded GCT over a wide range of speeds. However, results showed only moderate validity for the OJ system, with increasing errors when speed decreased. In conclusion, the PW proved to be a highly useful and valid application, and its use can be recommended not only for laboratory settings but also for field applications. In contrast, data on GCT obtained by OJ during running must be treated with caution, specifically when running speed changes or when comparisons are made with GCT data collected by other measurement systems. PMID- 26677826 TI - Effects of Acutely Intermittent Hypoxic Exposure on Running Economy and Physical Performance in Basketball Players. AB - Kilding, AE, Dobson, BP, and Ikeda, E. Effects of acutely intermittent hypoxic exposure on running economy and physical performance in basketball players. J Strength Cond Res 30(7): 2033-2042, 2016-The aim of this study was to determine the effect of short duration intermittent hypoxic exposure (IHE) on physical performance in basketball players. Using a single-blind placebo-controlled group design, 14 trained basketball players were subjected to 15 days of passive short duration IHE (n = 7), or normoxic control (CON, n = 7), using a biofeedback nitrogen dilution device. A range of physiological, performance, and hematological variables were measured at baseline, and 10 days after IHE. After intervention, the IHE group, relative to the CON group, exhibited improvements in the Yo-Yo intermittent recovery level 1 (+4.8 +/- 1.6%; effect size [ES]: 1.0 +/- 0.4) and repeated high-intensity exercise test performance (-3.5 +/- 1.6%; ES: 0.4 +/- 0.2). Changes in hematological parameters were minimal, although soluble transferrin receptor increased after IHE (+9.2 +/- 10.1%; ES: 0.3 +/- 0.3). Running economy at 11 km.h (-9.0 +/- 9.7%; ES: -0.7 +/- 0.7) and 13 km.h was improved (-8.2 +/- 6.9%; ES: -0.7 +/- 0.5), but changes to V[Combining Dot Above]O2peak, HRpeak, and lactate were unclear. In summary, acutely IHE resulted in worthwhile changes in physical performance tests among competitive basketball players. However, physiological measures explaining the performance enhancement were in most part unclear. PMID- 26677825 TI - Twist1 contributes to cranial bone initiation and dermal condensation by maintaining Wnt signaling responsiveness. AB - BACKGROUND: Specification of cranial bone and dermal fibroblast progenitors in the supraorbital arch mesenchyme is Wnt/beta-catenin signaling-dependent. The mechanism underlying how these cells interpret instructive signaling cues and differentiate into these two lineages is unclear. Twist1 is a target of the Wnt/beta-catenin signaling pathway and is expressed in cranial bone and dermal lineages. RESULTS: Here, we show that onset of Twist1 expression in the mouse cranial mesenchyme is dependent on ectodermal Wnts and mesenchymal beta-catenin activity. Conditional deletion of Twist1 in the supraorbital arch mesenchyme leads to cranial bone agenesis and hypoplastic dermis, as well as craniofacial malformation of eyes and palate. Twist1 is preferentially required for cranial bone lineage commitment by maintaining Wnt responsiveness. In the conditional absence of Twist1, the cranial dermis fails to condense and expand apically leading to extensive cranial dermal hypoplasia with few and undifferentiated hair follicles. CONCLUSIONS: Thus, Twist1, a target of canonical Wnt/beta-catenin signaling, also functions to maintain Wnt responsiveness and is a key effector for cranial bone fate selection and dermal condensation. PMID- 26677828 TI - G Allele of the IGF2 ApaI Polymorphism Is Associated With Judo Status. AB - Itaka, T, Agemizu, K, Aruga, S, and Machida, S. G allele of the IGF2 ApaI polymorphism is associated with judo status. J Strength Cond Res 30(7): 2043 2048, 2016-Previous studies have reported that the insulin-like growth factor 2 (IGF2) ApaI polymorphism is associated with body mass index, fat mass, and grip strength. Competitive judo requires high levels of strength and power. The purpose of this study was to investigate the association between the IGF2 ApaI and ACTN3 R577X polymorphisms and judo status. The subjects were 156 male judo athletes from a top-level university in Japan. They were divided into 3 groups based on their competitive history: international-level athletes, national-level athletes, and others. Genomic DNA was extracted from the saliva of each athlete, and the maximal isometric strength of the trunk muscles and handgrip strength were measured. Genotyping by polymerase chain reaction-restriction fragment length polymorphism was used to detect IGF2 (rs680) and alpha-actinin-3 (ACTN3) (rs1815739) gene polymorphisms. The genotype frequencies of the 2 gene polymorphisms were compared among the 3 groups of judo athletes and controls. International-level judo athletes showed a higher frequency of the GG + GA genotype of the IGF2 gene than that of the national-level athletes and others. There was an inverse linear correlation between the frequency of the IGF2 AA genotype and level of judo performance (p = 0.041). Back muscle strength relative to height and weight was higher in subjects with the GG + GA genotype than in those with the AA genotype. Conversely, the ACTN3 R577X polymorphism was not associated with judo status. Additionally, no differences were found in back muscle or handgrip strength among the ACTN3 genotypes. In conclusion, the results indicate that the IGF2 gene polymorphism may be associated with judo status. PMID- 26677829 TI - Ultrasound Changes in Achilles Tendon and Gastrocnemius Medialis Muscle on Squat Eccentric Overload and Running Performance. AB - Sanz-Lopez, F, Berzosa Sanchez, C, Hita-Contreras, F, Cruz-Diaz, D, and Martinez Amat, A. Ultrasound changes in Achilles tendon and gastrocnemius medialis muscle on squat eccentric overload and running performance. J Strength Cond Res XX(X): 000-000, 2015-Previous studies have proven the adaptation to load in the Achilles tendon and gastrocnemius muscle after different types of exercise, such as running, heel drop training, and a variety of sports. These findings have been applied to improve performance and in the treatment and prevention of overuse injuries. However, the effects that squat performance may have on the Achilles tendon and gastrocnemius muscle are still unknown. Squats are a widely used training exercise that involves calf-muscle activation. Similarly, no reports have been published regarding the adaptation to load of trained and untrained subjects during several consecutive days of running. The purpose of this study was to analyze changes in the Achilles tendon and in the pennation angles of the gastrocnemius medialis after eccentric overload training and within 3 days of running. Twenty healthy males who volunteered for this study were divided into 2 groups. Subjects in the eccentric overload training (ECC) group performed 6 weeks of eccentric overload training (twice weekly, 4 sets of 7 repetitions in a Yoyo squat device) before the running intervention. All participants, ECC and control (CONT) groups, ran on 3 consecutive days. After the eccentric training, an increase in the cross-sectional area of the Achilles tendon and in the pennation angle was observed. As for the running intervention, the behavior of tissues in both groups was similar. These results suggest that eccentric overload training with squats promotes changes in the Achilles tendon and in the pennation angle of the gastrocnemius medialis muscle. Nevertheless, significant changes in the tissue do not appear between the running performance of trained and untrained subjects. PMID- 26677830 TI - Concurrent Training in Prepubescent Children: The Effects of 8 Weeks of Strength and Aerobic Training on Explosive Strength and V[Combining Dot Above]O2max. AB - Alves, AR, Marta, CC, Neiva, HP, Izquierdo, M, and Marques, MC. Concurrent training in prepubescent children: the effects of 8 weeks of strength and aerobic training on explosive strength and V[Combining Dot Above]O2max. J Strength Cond Res 30(7): 2019-2032, 2016-The purpose of this study was to compare the effects of 8-week training periods of strength training alone (GS), combined strength and aerobic training in the same session (GCOM1), or in 2 different sessions (GCOM2) on explosive strength and maximal oxygen uptake (V[Combining Dot Above]O2max) in prepubescent children. Of note, 168 healthy children, aged 10-11 years (10.9 +/- 0.5), were randomly selected and assigned to 3 training groups to train twice a week for 8 weeks: GS (n = 41), GCOM1 (n = 45), GCOM2 (n = 38) groups, and a control group (GC) (n = 44; no training program). The GC maintained the baseline level, and trained-induced differences were found in the experimental groups. Differences were observed in the 1 and 3-kg medicine ball throws (GS: +5.8 and +8.1%, respectively; GCOM1: +5.7 and +8.7%, respectively; GCOM2: +6.2 and +8%, respectively, p < 0.001) and in the countermovement jump height and in the standing long jump length (GS: +5.1 and +5.2%, respectively; GCOM1: +4.2 and +7%, respectively; GCOM2: +10.2 and +6.4%, respectively, p < 0.001). In addition, the training period induced gains in the 20-m time (GS: +2.1%; GCOM1: +2.1%; GCOM2: +2.3%, p < 0.001). It was shown that the experimental groups (GCOM1, GCOM2, and GS) increased V[Combining Dot Above]O2max, muscular strength, and explosive strength from pretraining to posttraining. The higher gains were observed for concurrent training when it was performed in different sessions. These results suggest that concurrent training in 2 different sessions seems to be an effective and useful method for training-induced explosive strength and V[Combining Dot Above]O2max in prepubescent children. This could be considered as an alternative way to optimize explosive strength training and cardiorespiratory fitness in school-based programs. PMID- 26677831 TI - Rhabdomyolysis After Performing Blood Flow Restriction Training: A Case Report. AB - Tabata, S, Suzuki, Y, Azuma, K, and Matsumoto, H. Rhabdomyolysis after performing blood flow restriction training: a case report. J Strength Cond Res 30(7): 2064 2068, 2016-Rhabdomyolysis is a serious and potentially life-threatening condition related to resistance training. Despite numerous reports of low-intensity blood flow restriction (BFR) training inducing muscle hypertrophy and increasing strength, few reports of rhabdomyolysis related to BFR training have been published. Here, we report a 30-year-old obese Japanese man admitted to our hospital the day after his first BFR training session with complaints of severe muscle pain in his upper and lower extremities, high fever, and pharyngeal pain. He was diagnosed with acute rhabdomyolysis based on a serum creatine phosphokinase level of 56,475 U.L and a urine myoglobin level of >3,000 ng.ml, and with acute tonsillitis based on a white blood cell count of 17,390 and C reactive protein level of 10.43 mg.dl. A number of factors are suspected to be related to the onset and exacerbation of rhabdomyolysis, including excessive muscular training with BFR, bacterial infection, and medication. After 10 days of hospitalization with intravenous fluids and antibacterial drugs, he recovered without complications. This case indicates that BFR training should be conducted with careful consideration of the physical condition and strength of the individual to prevent serious complications, such as rhabdomyolysis. PMID- 26677832 TI - Ball Speed and Release Consistency Predict Pitching Success in Major League Baseball. AB - Whiteside, D, Martini, DN, Zernicke, RF, and Goulet, GC. Ball speed and release consistency predict pitching success in Major League Baseball. J Strength Cond Res XX(X): 000-000, 2015-This study aimed to quantify how ball flight kinematics (i.e., ball speed and movement), release location, and variations therein relate to pitching success in Major League Baseball (MLB). One hundred ninety starting MLB pitchers met the inclusion criteria for this study. Ball trajectory information was collected for 76,000 pitches and inserted into a forward stepwise multiple regression model, which examined how (a) pitch selection, (b) ball speed, (c) ball movement (horizontal and lateral), (d) release location (horizontal and lateral), (e) variation in pitch speed, (f) variation in ball movement, and (g) variation in release location related to pitching success (as measured by fielding independent pitching-FIP). Pitch speed, release location variability, variation in pitch speed, and horizontal release location were significant predictors of FIP and, collectively, accounted for 24% of the variance in FIP. These findings suggest that (a) maximizing ball speed, (b) refining a consistent spatial release location, and (c) using varied pitch speeds should be primary foci for the pitching coach. However, between-pitcher variations underline how training interventions should be administered at the individual level, with consideration given to the pitcher's injury history. Finally, despite offering significant predictors of success, these three factors explained only 22% of the variance in FIP and should not be considered the only, or preeminent, indicators of a pitcher's effectiveness. Evidently, traditional pitching metrics only partly account for a pitcher's effectiveness, and future research is necessary to uncover the remaining contributors to success. PMID- 26677833 TI - Influence of Pedaling Cadence and Incremental Protocol on the Estimation of EMGFT. AB - Duff, TM, Fournier, H, Hopp, OB, Ochshorn, E, Sanders, ES, Stevens, RE, and Malek, MH. Influence of pedaling cadence and incremental protocol on the estimation of EMGFT. J Strength Cond Res 30(8): 2206-2211, 2016-Theoretically, the electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that an individual can exercise at indefinitely without an increase in electromyography (EMG) amplitude. This index is estimated from a single incremental test. There are, however, factors that may influence EMG amplitude such as pedaling cadence or the incremental protocol used. The purposes of this study were to determine whether different pedaling cadences and/or incremental protocols influence the estimation of the EMGFT. Eight healthy college-aged men performed incremental cycle ergometry on three separate visits. The participants exercised using the following combinations of pedaling cadences and incremental protocols in random order: 25 W at 70 RPM; 13 W at 70 RPM; and 25 W at 100 RPM. The EMGFT value was determined from the vastus lateralis muscle of each participant for each of the three conditions. Separate 1-way repeated measures analysis of variances were performed to determine mean differences for various outcome indices. The mean maximal power output for the 13 W at 70 RPM condition was significantly lower than the two other conditions. There were, however, no significant mean differences (F (2,14) = 2.03; p = 0.169) for EMGFT between the three conditions. The findings of this study indicated that different pedaling cadences and incremental protocols did not influence the estimation of the EMGFT. PMID- 26677834 TI - Effect of exogenous hydrogen sulfide on gastric acid secretion. AB - BACKGROUND AND AIM: H2 S is an important gasotransmitter in the gastrointestinal tract. The aim of the present study was to investigate the effect of exogenous H2 S on gastric acid secretion. METHODS: Male Wistar rats were randomly divided into physiological saline (PS) group, sodium hydrosulfide (NaHS; 50, 100, and 150 umol/kg body weight) group, glibenclamide + NaHS group, and SQ22536 + NaHS group. PH of gastric juice before injection and after injection were determined by a PH meter. RESULTS: The results showed that NaHS, an exogenous H2 S donor, injected into the enterocoelia significantly reduced the PH of gastric juice, the same volume of PS administered similarly did not change PH of gastric juice, the promotional effect of NaHS on gastric acid secretion could be abolished by glibenclamide, an ATP-sensitive potassium channel K(ATP) blocker SQ22536, an inhibitor of adenyl cyclase. CONCLUSIONS: The data from these experiments suggest that exogenous H2 S promoted gastric acid secretion, which may occur via K(ATP) channels and activate AC-cAMP pathway. PMID- 26677836 TI - Letter to the Editor. PMID- 26677837 TI - A regulatory perspective on missing data in the aftermath of the NRC report. AB - The issuance of a report in 2010 by the National Research Council (NRC) of the National Academy of Sciences entitled 'The Prevention and Treatment of Missing Data in Clinical Trials,' commissioned by the US Food and Drug Administration, had an immediate impact on the way that statisticians and clinical researchers in both industry and regulatory agencies think about the missing data problem. We believe that there is currently great potential to improve study quality and interpretability-by reducing the amount of missing data through changes in trial design and conduct and by planning and conducting analyses that better account for the missing information. Here, we describe our view on some of the recommendations in the report and suggest ways in which these recommendations can be incorporated into new or ongoing clinical trials in order to improve their chance of success. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26677835 TI - Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review. AB - BACKGROUND: Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. OBJECTIVE: The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. METHODS: A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term "Direct-to-consumer genetic test." RESULTS: In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers' health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk appropriately. CONCLUSIONS: The impact of DTC-GT on consumers' health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact. PMID- 26677839 TI - Y-chromosome distributions among populations in Northwest China identify significant contribution from Central Asian pastoralists and lesser influence of western Eurasians. PMID- 26677840 TI - Costs of postabortion care in public sector health facilities in Malawi: a cross sectional survey. AB - BACKGROUND: Health systems could obtain substantial cost savings by providing safe abortion care rather than providing expensive treatment for complications of unsafely performed abortions. This study estimates current health system costs of treating unsafe abortion complications and compares these findings with newly projected costs for providing safe abortion in Malawi. METHODS: We conducted in depth surveys of medications, supplies, and time spent by clinical personnel dedicated to postabortion care (PAC) for three treatment categories (simple, severe non-surgical, and severe surgical complications) and three uterine evacuation (UE) procedure types (manual vacuum aspiration (MVA), dilation and curettage (D&C) and misoprostol-alone) at 15 purposively-selected public health facilities. Per-case treatment costs were calculated and applied to national, annual PAC caseload data. RESULTS: The median cost per D&C case ($63) was 29% higher than MVA treatment ($49). Costs to treat severe non-surgical complications ($63) were almost five times higher than those of a simple PAC case ($13). Severe surgical complications were especially costly to treat at $128. PAC treatment in public facilities cost an estimated $314,000 annually. Transition to safe, legal abortion would yield an estimated cost reduction of 20%-30%. CONCLUSIONS: The method of UE and severity of complications have a large impact on overall costs. With a liberalized abortion law and implementation of induced abortion services with WHO-recommended UE methods, current PAC costs to the health system could markedly decrease. PMID- 26677838 TI - Simultaneous detection of four different neuraminidase types of avian influenza A H5 viruses by multiplex reverse transcription PCR using a GeXP analyser. AB - OBJECTIVES: In order to develop a multiplex RT-PCR assay using the GeXP analyser for the simultaneous detection of four different NA serotypes of H5-subtype AIVs, effective to control and reduce H5 subtype of avian influenza outbreak. DESIGN: Six pairs of primers were designed using conserved and specific sequences of the AIV subtypes H5, N1, N2, N6 and N8 in GenBank. Each gene-specific primer was fused at the 5' end to a universal sequence to generate six pairs of chimeric primers, and one pair of universal primers was used for RT-PCR, and PCR product separation and detection were performed by capillary electrophoresis using the GenomeLab GeXP genetic analysis system. SETTING: Single and mixed avian pathogen cDNA/DNA templates were employed to evaluate the specificity of a multiplex assay with a GeXP analyser. Corresponding specific DNA products were amplified for each gene, revealing amplification peaks for M, H5, N1, N2, N6 and N8 genes from four different NA subtypes of influenza A H5 virus. SAMPLE: A total of 180 cloacal swabs were collected from poultry at live bird markets. MAIN OUTCOME MEASURES: The multiplex PCR assay demonstrated excellent specificity, with each pair of specific primers generating only products corresponding to the target genes and without cross-amplification with other NA-subtype influenza viruses or other avian pathogens. Using various premixed ssRNAs containing known AIV target genes, the detection limit for the multiplex assay was determined to be 10(2) copies/MUl. The GeXP assay was further evaluated using 180 clinical specimens and compared with RRT-PCR (real-time reverse transcriptase PCR) and virus isolation. CONCLUSIONS: This GeXP analyser-based multiplex assay for four different NA subtypes of H5 HPAI viruses is both highly specific and sensitive and can be used as a rapid and direct diagnostic assay for testing clinical samples. PMID- 26677841 TI - Avian Influenza Ecology in North Atlantic Sea Ducks: Not All Ducks Are Created Equal. AB - Wild waterfowl are primary reservoirs of avian influenza viruses (AIV). However the role of sea ducks in the ecology of avian influenza, and how that role differs from freshwater ducks, has not been examined. We obtained and analyzed sera from North Atlantic sea ducks and determined the seroprevalence in those populations. We also tested swab samples from North Atlantic sea ducks for the presence of AIV. We found relatively high serological prevalence (61%) in these sea duck populations but low virus prevalence (0.3%). Using these data we estimated that an antibody half-life of 141 weeks (3.2 years) would be required to attain these prevalences. These findings are much different than what is known in freshwater waterfowl and have implications for surveillance efforts, AIV in marine environments, and the roles of sea ducks and other long-lived waterfowl in avian influenza ecology. PMID- 26677842 TI - Diagnostic value of cerebrospinal fluid Abeta ratios in preclinical Alzheimer's disease. AB - INTRODUCTION: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) Abeta ratios rather than Abeta42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). METHODS: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent (18)F flutemetamol PET and CSF measurement of Abeta1-42, Abeta1-40, Abeta1-38, and total tau (ttau). (18)F-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and (18)F-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. RESULTS: Seven out of 38 subjects (18 %) were positive on amyloid PET. Abeta42/ttau, Abeta42/Abeta40, Abeta42/Abeta38, and Abeta42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) >= 0.908). Abeta40 and Abeta38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, Abeta42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of Abeta42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). CONCLUSION: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of Abeta42/ttau rather than using Abeta42 in isolation. PMID- 26677843 TI - Clinical parameters related to metamorphopsia outcome in patients with resolved central serous chorioretinopathy using M-CHARTS: retrospective cohort study. AB - BACKGROUND: The purpose of this study was to determine the clinical parameters related to metamorphopsia outcome in patients with resolved central serous chorioretinopathy (CSCR). METHODS: The charts of 36 eyes with resolved CSCR were retrospectively reviewed. We measured metamorphopsia using M-CHARTS after resolution of serous retinal detachment. We analyzed the relationship between metamorphopsia outcome and clinical parameters including age, visual acuity, chronicity of CSCR, symptom duration and several spectral-domain optical coherence tomography findings using univariate and multivariate forward logistic regression analyses. RESULTS: The M-CHARTS detected metamorphopsia in 19 eyes (52.8 %). In the univariate analysis, the eyes with metamorphopsia were, relative to those without metamorphopsia, significantly associated with a greater proportion of chronic-recurrent CSCR, initial and final irregularities of retinal pigment epithelium, longer symptom duration, thinner final thickness of central fovea and outer nuclear layer, and final disruption of external limiting membrane (ELM), photoreceptor inner and outer segment junction and cone outer segment tip line (P = 0.003, 0.037, 0.019, 0.003, 0.013, 0.015, <0.001, 0. 012 and 0.002, respectively). However, in the multivariate analysis, chronic-recurrent CSCR (OR 22.5, P = 0.019) and final disrupted ELM (OR 82.6, P = 0.004) were the independent clinical parameters related to poor metamorphopsia outcome. CONCLUSIONS: Residual metamorphopsia was detected using M-CHARTS in about half of patients (52.8 %) with resolved CSCR. Chronic-recurrent CSCR and final disrupted ELM were the independent clinical parameters related to poor metamorphopsia outcome in patients with resolved CSCR. PMID- 26677844 TI - Bayesian estimation of associations between identified longitudinal hormone subgroups and age at final menstrual period. AB - BACKGROUND: Although follicle stimulating hormone (FSH) is known to be predictive of age at final menstrual period (FMP), previous methods use FSH levels measured at time points that are defined relative to the age at FMP, and hence are not useful for prospective prediction purposes in clinical settings where age at FMP is an unknown outcome. This study is aimed at assessing whether FSH trajectory feature subgroups identified relative to chronological age can be used to improve the prediction of age at FMP. METHODS: We develop a Bayesian model to identify latent subgroups in longitudinal FSH trajectories, and study the relationship between subgroup membership and age at FMP. Data for our study is taken from the Penn Ovarian Aging study, 1996-2010. The proposed model utilizes mixture modeling and nonparametric smoothing methods to capture hypothesized latent subgroup features of the FSH longitudinal trajectory; and simultaneously studies the prognostic value of these latent subgroup features to predict age at FMP. RESULTS: The analysis identified two FSH trajectory subgroups that were significantly associated with FMP age: 1) early FSH class (15%), which displayed initial increases in FSH shortly after age 40; and 2) late FSH class (85%), which did not have a rise in FSH until after age 45. The use of FSH subgroup memberships, along with class-specific characteristics, i.e., level and rate of FSH change at class-specific pre-specified ages, improved prediction of FMP age by 20-22% in comparison to the prediction based on previously identified risk factors (BMI, smoking and pre-menopausal levels of anti-mullerian hormone (AMH)). CONCLUSIONS: To the best of our knowledge, this work is the first in the area to demonstrate the existence of subgroups in FSH trajectory patterns relative to chronological age and the fact that such a subgroup membership possesses prediction power for age at FMP. Earlier ages at FMP were found in a subgroup of women with rise in FSH levels commencing shortly after age 40, in comparison to women who did not exhibit an increase in FSH until after 45 years of age. Periodic evaluations of FSH in these age ranges are potentially useful for predicting age at FMP. PMID- 26677847 TI - Cost inefficiency under financial strain: a stochastic frontier analysis of hospitals in Washington State through the Great Recession. AB - The importance of increasing cost efficiency for community hospitals in the United States has been underscored by the Great Recession and the ever-changing health care reimbursement environment. Previous studies have shown mixed evidence with regards to the relationship between linking hospitals' reimbursement to quality of care and cost efficiency. Moreover, current evidence suggests that not only inherently financially disadvantaged hospitals (e.g., safety-net providers), but also more financially stable providers, experienced declines to their financial viability throughout the recession. However, little is known about how hospital cost efficiency fared throughout the Great Recession. This study contributes to the literature by using stochastic frontier analysis to analyze cost inefficiency of Washington State hospitals between 2005 and 2012, with controls for patient burden of illness, hospital process of care quality, and hospital outcome quality. The quality measures included in this study function as central measures for the determination of recently implemented pay-for performance programs. The average estimated level of hospital cost inefficiency before the Great Recession (10.4 %) was lower than it was during the Great Recession (13.5 %) and in its aftermath (14.1 %). Further, the estimated coefficients for summary process of care quality indexes for three health conditions (acute myocardial infarction, pneumonia, and heart failure) suggest that higher quality scores are associated with increased cost inefficiency. PMID- 26677845 TI - Evidence for the recent origin of a bacterial protein-coding, overlapping orphan gene by evolutionary overprinting. AB - BACKGROUND: Gene duplication is believed to be the classical way to form novel genes, but overprinting may be an important alternative. Overprinting allows entirely novel proteins to evolve de novo, i.e., formerly non-coding open reading frames within functional genes become expressed. Only three cases have been described for Escherichia coli. Here, a fourth example is presented. RESULTS: RNA sequencing revealed an open reading frame weakly transcribed in cow dung, coding for 101 residues and embedded completely in the -2 reading frame of citC in enterohemorrhagic E. coli. This gene is designated novel overlapping gene, nog1. The promoter region fused to gfp exhibits specific activities and 5' rapid amplification of cDNA ends indicated the transcriptional start 40-bp upstream of the start codon. nog1 was strand-specifically arrested in translation by a nonsense mutation silent in citC. This Nog1-mutant showed a phenotype in competitive growth against wild type in the presence of MgCl2. Small differences in metabolite concentrations were also found. Bioinformatic analyses propose Nog1 to be inner membrane-bound and to possess at least one membrane-spanning domain. A phylogenetic analysis suggests that the orphan gene nog1 arose by overprinting after Escherichia/Shigella separated from the other gamma-proteobacteria. CONCLUSIONS: Since nog1 is of recent origin, non-essential, short, weakly expressed and only marginally involved in E. coli's central metabolism, we propose that this gene is in an initial stage of evolution. While we present specific experimental evidence for the existence of a fourth overlapping gene in enterohemorrhagic E. coli, we believe that this may be an initial finding only and overlapping genes in bacteria may be more common than is currently assumed by microbiologists. PMID- 26677848 TI - Correction: miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer. PMID- 26677846 TI - Systematic Review of the Side Effects Associated With Anti-HER2-Targeted Therapies Used in the Treatment of Breast Cancer, on Behalf of the EORTC Quality of Life Group. AB - PURPOSE: Targeted therapies (TTs), notably trastuzumab, have improved outcomes for breast cancer characterised by overexpression of human epidermal growth factor receptors including HER2. Compared with chemotherapy treatments, TTs are more specific in their targets and are delivered over longer periods of time, thus presenting different side-effect profiles. The objective of this paper is to systematically review and describe the side effects associated with TTs used in the adjuvant and metastatic settings for HER2+ breast cancer. METHODS: The MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library databases were searched from January 2007 to March 2015 to identify clinical trials and prospective studies reporting toxicities associated with TTs (mainly trastuzumab and lapatinib) used without other therapies in the treatment of HER2-positive breast cancer. Two independent reviewers selected papers based on their titles and abstracts. All papers selected by either reviewer were included. A third reviewer extracted and tabulated the relevant data using a data extraction form. RESULTS: We identified 5478 papers, of which 299 were reviewed and 18 trials identified involving 6980 patients. A total of 66 side effects were identified, including 46 "patient-based" symptoms and 20 "medically defined" outcomes. Side effects were more common for patients treated with therapies other than trastuzumab or with dual-HER2 regimens and for patients with metastatic disease. Diarrhoea and skin rash were the most prevalent symptoms, experienced by 29 % and 22 % of patients overall, respectively. There were 119 (2 %) cardiac events reported, and these were not exclusive to trastuzumab-treated patients. The majority of side effects (n = 52) were experienced by 1 % or less of patients and were predominantly of grade 1/2 toxicity. CONCLUSIONS: This systematic review provides a detailed analysis of side effects of HER2+ therapies in a large number of patients included in trials, enabling an accurate estimate of prevalence and a complete understanding of the patients' experience. This will help clinicians and patients in treatment planning. PMID- 26677849 TI - Evaluating Propensity Score Methods in a Quasi-Experimental Study of the Impact of Menu-Labeling. AB - BACKGROUND: Quasi-experimental studies of menu labeling have found mixed results for improving diet. Differences between experimental groups can hinder interpretation. Propensity scores are an increasingly common method to improve covariate balance, but multiple methods exist and the improvements associated with each method have rarely been compared. In this re-analysis of the impact of menu labeling, we compare multiple propensity score methods to determine which methods optimize balance between experimental groups. METHODS: Study participants included adult customers who visited full-service restaurants with menu labeling (treatment) and without (control). We compared the balance between treatment groups obtained by four propensity score methods: 1) 1:1 nearest neighbor matching (NN), 2) augmented 1:1 NN (using caliper of 0.2 and an exact match on an imbalanced covariate), 3) full matching, and 4) inverse probability weighting (IPW). We then evaluated the treatment effect on differences in nutrients purchased across the different methods. RESULTS: 1:1 NN resulted in worse balance than the original unmatched sample (average standardized absolute mean distance [ASAM]: 0.185 compared to 0.171). Augmented 1:1 NN improved balance (ASAM: 0.038) but resulted in a large reduction in sample size. Full matching and IPW improved balance over the unmatched sample without a reduction in sample size (ASAM: 0.049 and 0.031, respectively). Menu labeling was associated with decreased calories, fat, sodium and carbohydrates in the unmatched analysis. Results were qualitatively similar in the propensity score matched/weighted models. CONCLUSIONS: While propensity scores offer an increasingly popular tool to improve causal inference, choosing the correct method can be challenging. Our results emphasize the benefit of examining multiple methods to ensure results are consistent, and considering approaches beyond the most popular method of 1:1 NN matching. PMID- 26677850 TI - Influence of Chirality of Crizotinib on Its MTH1 Protein Inhibitory Activity: Insight from Molecular Dynamics Simulations and Binding Free Energy Calculations. AB - As a promising target for the treatment of lung cancer, the MutT Homolog 1 (MTH1) protein can be inhibited by crizotinib. A recent work shows that the inhibitory potency of (S)-crizotinib against MTH1 is about 20 times over that of (R) crizotinib. But the detailed molecular mechanism remains unclear. In this study, molecular dynamics (MD) simulations and free energy calculations were used to elucidate the mechanism about the effect of chirality of crizotinib on the inhibitory activity against MTH1. The binding free energy of (S)-crizotinib predicted by the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Adaptive biasing force (ABF) methodologies is much lower than that of (R) crizotinib, which is consistent with the experimental data. The analysis of the individual energy terms suggests that the van der Waals interactions are important for distinguishing the binding of (S)-crizotinib and (R)-crizotinib. The binding free energy decomposition analysis illustrated that residues Tyr7, Phe27, Phe72 and Trp117 were important for the selective binding of (S) crizotinib to MTH1. The adaptive biasing force (ABF) method was further employed to elucidate the unbinding process of (S)-crizotinib and (R)-crizotinib from the binding pocket of MTH1. ABF simulation results suggest that the reaction coordinates of the (S)-crizotinib from the binding pocket is different from (R) crizotinib. The results from our study can reveal the details about the effect of chirality on the inhibition activity of crizotinib to MTH1 and provide valuable information for the design of more potent inhibitors. PMID- 26677851 TI - Integration of Chiropractic Services in Military and Veteran Health Care Facilities: A Systematic Review of the Literature. AB - This literature review examined studies that described practice, utilization, and policy of chiropractic services within military and veteran health care environments. A systematic search of Medline, CINAHL, and Index to Chiropractic Literature was performed from inception through April 2015. Thirty articles met inclusion criteria. Studies reporting utilization and policy show that chiropractic services are successfully implemented in various military and veteran health care settings and that integration varies by facility. Doctors of chiropractic that are integrated within military and veteran health care facilities manage common neurological, musculoskeletal, and other conditions; severe injuries obtained in combat; complex cases; and cases that include psychosocial factors. Chiropractors collaboratively manage patients with other providers and focus on reducing morbidity for veterans and rehabilitating military service members to full duty status. Patient satisfaction with chiropractic services is high. Preliminary findings show that chiropractic management of common conditions shows significant improvement. PMID- 26677852 TI - Proposal for a descriptive guideline of vascular changes in lesions of the vocal folds by the committee on endoscopic laryngeal imaging of the European Laryngological Society. AB - In the last decades new endoscopic tools have been developed to improve the diagnostic work-up of vocal fold lesions in addition to normal laryngoscopy, i.e., contact endoscopy, autofluorescence, narrow band imaging and others. Better contrasted and high definition images offer more details of the epithelial and superficial vascular structure of the vocal folds. Following these developments, particular vascular patterns come into focus during laryngoscopy. The present work aims at a systematic pathogenic description of superficial vascular changes of the vocal folds. Additionally, new nomenclature on vascular lesions of the vocal folds will be presented to harmonize the different terms in the literature. Superficial vascular changes can be divided into longitudinal and perpendicular. Unlike longitudinal vascular lesions, e.g., ectasia, meander and change of direction, perpendicular vascular lesions are characterized by different types of vascular loops. They are primarily observed in recurrent respiratory papillomatosis, and in pre-cancerous and cancerous lesions of the vocal folds. These vascular characteristics play a significant role in the differential diagnosis. Among different parameters, e.g., epithelial changes, increase of volume, stiffness of the vocal fold, vascular lesions play an increasing role in the diagnosis of pre- and cancerous lesions. PMID- 26677853 TI - Effect of supplemental oxygen 80 % on post-tonsillectomy nausea and vomiting: a randomized controlled trial. AB - Nausea and vomiting are two of the most common complications of tonsillectomy in children. Administration of supplemental 80 % oxygen during surgery reduces the incidence of postoperative nausea and vomiting. We aimed to test the efficacy of supplemental 80 % oxygen during tonsillectomy on postoperative nausea and vomiting. In a randomized controlled trial in Shahid Mostafa Khomeini Hospital in Tehran, 102 children scheduled for tonsillectomy (+/- adenoidectomy) under general anesthesia were divided randomly in two groups according to percent of administered oxygen (group 1:30 % oxygen, group 2:80 % oxygen). The incidence of postoperative nausea and vomiting were assessed and compared in 0-2, 2-6 and 6-24 h after surgery. Incidence of post-tonsillectomy nausea and vomiting after 2, 2 6, and 6-24 h was 13.72, 1.96 and 1.96 % for group 1 and 3.92, 0 and 1.96 % in group 2, respectively. We found no statistically significant difference between two groups (P = 0.08) but 80 % oxygen was beneficial for reducing postoperative nausea and vomiting in the first 2 h after surgery in group 2. PMID- 26677854 TI - Role of Glucocorticoids in Cystic Ovarian Disease: Expression of Glucocorticoid Receptor in the Bovine Ovary. AB - The aim of this study was to characterize the expression of glucocorticoid receptor (GR) in the components of normal bovine ovary and in animals with cystic ovarian disease (COD). Changes in the protein and mRNA expression levels were determined in control cows and cows with COD by immunohistochemistry and real time PCR. GR protein expression in granulosa cells was higher in cysts from animals with spontaneous COD and adrenocorticotropic hormone-induced COD than in tertiary follicles from control animals. In theca interna cells, GR expression was higher in cysts from animals with spontaneous COD than in tertiary follicles from control animals. The increase in GR expression observed in cystic follicles suggests a mechanism of action for cortisol and its receptor through the activation/inactivation of specific transcription factors. These factors could be related to the pathogenesis of COD in cattle. PMID- 26677856 TI - [Narrow band imaging for early diagnosis of epithelial dysplasias and microinvasive tumors in the upper aerodigestive tract]. AB - The various stages of tumor growth are characterized by typical epithelial, vascular, and secondary connective tissue changes. Narrow band imaging (NBI) endoscopy is a minimally invasive imaging technique that presents vascular structures in particular at a higher contrast than white light endoscopy alone. In combination with high-resolution image recording and reproduction (high definition television, HDTV; ultra-high definition, 4K), progress has been made in otolaryngological differential diagnostics, both pre- and intraoperatively. This progress represents an important step towards a so-called optical biopsy. Flexible endoscopy in combination with NBI allows detailed assessment of areas of the upper aerodigestive tract which are difficult to assess by rigid endoscopy. Papillomas, precancerous, and cancerous lesions are characterized by epithelial and connective tissue changes, as well as by typical perpendicular vascular changes. Systematic use of NBI is recommended in the differential diagnosis of malignant lesions of the upper aerodigestive tract. NBI also convinces by a significant improvement in pre- and intraoperative assessment of superficial resection margins. In particular, the combination of NBI and contact endoscopy (compact endoscopy) permits excellent therapeutic decisions during tumor surgery. Intraoperative determination of resection margins at unprecedented precision is possible. In addition, assessment of the form and extent of the perpendicular vessel loops stimulated by epithelial signaling enables differential diagnostic decisions to be made, approximating our goal of an optical biopsy. PMID- 26677857 TI - Low parathyroid hormone levels after parathyroidectomy reduce cardiovascular mortality in chronic hemodialysis patients. AB - BACKGROUND: The aim of the study is to elucidate whether parathyroid hormone (PTH) levels after parathyroidectomy affect the prognosis of patients with secondary hyperparathyroidism. SUBJECTS AND METHODS: Two hundred and ninety-five patients, who underwent PTx without autotransplantation from July 1998 to December 2011, were divided into the low (n = 148) and high (n = 147) PTH groups, using the median value of each mean value of intact PTH after surgery (16.6 pg/mL). After observation for 5.00 years, we evaluated demographic factors, influences of postoperative mineral metabolism, magnitude of uremia, and vitamin D receptor activators on their prognosis, with the multivariate Cox proportional hazard model. RESULTS: While overall survival rates in the high and low PTH groups were 54.9 and 74.2 %, respectively (P = 0.1500), cardiovascular survival rates were 71.6 and 94.4 %, respectively (P = 0.0256). The hazard ratio for cardiovascular mortality in the high PTH group (>=16.6 pg/mL) was 3.132 (P = 0.0470), and those in groups with the median age more than 59 years and with cardiovascular disease were 2.654 (P = 0.0589) and 3.377 (P = 0.0317), respectively. The intact PTH level 6 days after surgery and the mean postoperative intact PTH value showed a strong correlation (Spearman rho = 0.9007, P < 0.0001, y = 0.4725x + 30.395, R 2 = 0.51798). CONCLUSION: The present study suggests that maintaining low PTH levels after parathyroidectomy reduces cardiovascular mortality and improves the prognosis. Total parathyroidectomy (more than 4 glands) without autotransplantation seems to be one of the treatment options for managing severe secondary hyperparathyroidism. PMID- 26677858 TI - Endocrinology & Art. Virgin and child with Saint Anne by Albrecht Durer (1471 1528). PMID- 26677855 TI - Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity. AB - We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer's disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer's disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes. PMID- 26677859 TI - Development and Evaluation of a Once-Daily Controlled Porosity Osmotic Pump of Tapentadol Hydrochloride. AB - The present study aimed to prepare, optimize, and evaluate Tapentadol hydrochloride controlled porosity osmotic pump (CPOP) and to achieve the drug release at nearly zero-order. The CPOP was prepared by the coating of polymers (Eudragit RSPO and RLPO) on a directly compressed core tablet. A Box-behnken experimental design was applied to optimize the parameters for CPOP. The optimized batch was characterized for in vitro drug release study, effect of pH, osmolarity and agitation intensity, and surface morphology and stability study. In vivo pharmacokinetic studies were performed on New Zealand white rabbits for CPOP and marketed tablet. All the batches showed a drug release ranging from 29.87 to 56.92% after 12 h; and from 59.64 to 99.96% after 24 h. There was no change in the drug release pattern at different pH and agitation intensities. The drug release was found to decrease with increasing osmolarity of dissolution media.An in vivo study showed a higher mean residence time, area under the curve, and biological half-life (T 1/2) than the marketed tablet with low rate of elimination (Ke) and a 2.35-fold increase in relative bioavailability. The result showed that the amounts of sodium chloride and PEG 400 were contributing positively while the number of coats was negatively affecting the drug release. The drug release was found to be independent of physiological conditions. The stability testing showed that the prepared CPOP was stable for 3 months at accelerated conditions. The prepared CPOP was found to deliver Tapentadol hydrochloride at zero-order for up to 24 h. PMID- 26677860 TI - Allochthonous Carbon--a Major Driver of Bacterioplankton Production in the Subarctic Northern Baltic Sea. AB - Heterotrophic bacteria are, in many aquatic systems, reliant on autochthonous organic carbon as their energy source. One exception is low-productive humic lakes, where allochthonous dissolved organic matter (ADOM) is the major driver. We hypothesized that bacterial production (BP) is similarly regulated in subarctic estuaries that receive large amounts of riverine material. BP and potential explanatory factors were measured during May-August 2011 in the subarctic Rane Estuary, northern Sweden. The highest BP was observed in spring, concomitant with the spring river-flush and the lowest rates occurred during summer when primary production (PP) peaked. PLS correlations showed that ~60% of the BP variation was explained by different ADOM components, measured as humic substances, dissolved organic carbon (DOC) and coloured dissolved organic matter (CDOM). On average, BP was threefold higher than PP. The bioavailability of allochthonous dissolved organic carbon (ADOC) exhibited large spatial and temporal variation; however, the average value was low, ~2%. Bioassay analysis showed that BP in the near-shore area was potentially carbon limited early in the season, while BP at seaward stations was more commonly limited by nitrogen phosphorus. Nevertheless, the bioassay indicated that ADOC could contribute significantly to the in situ BP, ~60%. We conclude that ADOM is a regulator of BP in the studied estuary. Thus, projected climate-induced increases in river discharge suggest that BP will increase in subarctic coastal areas during the coming century. PMID- 26677861 TI - Development and Implementation of Clinical Pharmacist Services Within an Integrated Medical Group. AB - BACKGROUND: In 2012, pharmacists were integrated into a medical group to provide direct patient care, drug information activities, and health care provider education. The medical group encompasses 40 primary care and 60 specialty offices in Virginia. OBJECTIVE: To describe the development and implementation of clinical pharmacist services integrated within a medical group. METHODS: Pharmacists' roles and responsibilities, type and number of patient encounters, and identification of strategies to facilitate implementation are described. RESULTS: From June 2012 to December 2014, pharmacists had 809 patient encounters, which included patient-centered education, medication consults, Medicare annual wellness visits, senior care visits, and comprehensive medication reviews. Pharmacists addressed 403 drug information requests from nurse navigators, providers, and administrators. Pharmacists also have roles in risk management, quality improvement initiatives, and operations that benefit the medical group. Strategies to facilitate implementation include working with organizational leadership, identifying a physician champion, and establishing credibility by being responsive to practice needs and responding to requests in a timely manner to build trust within the health care team. CONCLUSION: Integration of pharmacists within health care teams involves more than direct patient care activities. Pharmacists should be involved at the organizational level to have a broader impact on patient and practice levels. PMID- 26677863 TI - Inhibition of EGF Receptor Blocks the Development and Progression of Peritoneal Fibrosis. AB - Inhibitors of EGF receptor (EGFR) have antifibrotic effects in several organs, but the effect of these inhibitors on the development of peritoneal fibrosis is unknown. Here, we explored the therapeutic effect of gefitinib, a specific inhibitor of EGFR, on the development and progression of peritoneal fibrosis in a rat model. Daily intraperitoneal injections of chlorhexidine gluconate induced peritoneal fibrosis, indicated by thickening of the submesothelial area with an accumulation of collagen fibrils and activation of myofibroblasts, accompanied by time-dependent phosphorylation of EGFR. Administration of gefitinib immediately after injury prevented the onset of peritoneal fibrosis and delayed administration after the onset of peritoneal fibrosis halted fibrosis progression. Gefitinib treatment abrogated the increased phosphorylation of EGFR, Smad3, signal transducer and activator of transcription 3, and NF-kappaB during peritoneal fibrosis; it also inhibited the accompanying overproduction of TGF beta1 and proinflammatory cytokines and the infiltration of macrophages to the injured peritoneum. Moreover, gefitinib significantly reduced the peritoneal increase of CD31-positive blood vessels and vascular EGF-positive cells after injury. Finally, gefitinib also attenuated high glucose-induced peritoneal fibrosis in rats and abrogated TGF-beta1-induced phosphorylation of Smad3 and the epithelial-to-mesenchymal transition of cultured human peritoneal mesothelial cells. These results demonstrate that EGFR contributes to peritoneal fibrosis, inflammation, and angiogenesis, suggesting that EGFR inhibitors may have therapeutic potential in attenuating peritoneal fibrosis. PMID- 26677864 TI - MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney Disease. AB - Autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4 Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD. PMID- 26677862 TI - Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial. AB - Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean+/-SD serum 25(OH)D increased from 16.0+/-5.9 ng/ml at baseline to 39.2+/-14.9 ng/ml in the ergocalciferol arm and did not change (16.9+/-6.4 ng/ml and 17.5+/-7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes. PMID- 26677866 TI - Magnetically Directed Two-Dimensional Crystallization of OmpF Membrane Proteins in Block Copolymers. AB - Two-dimensional (2D) alignment and crystallization of membrane proteins (MPs) is increasingly important in characterizing their three-dimensional (3D) structure, in designing pharmacological agents, and in leveraging MPs for biomimetic devices. Large, highly ordered MP 2D crystals in block copolymer (BCP) matrices are challenging to fabricate, but a facile and scalable technique for aligning and crystallizing MPs in thin-film geometries would rapidly translate into applications. This work introduces a novel method to grow larger and potentially better ordered 2D crystals by performing the crystallization process in the presence of a strong magnetic field. We demonstrate the efficacy of this approach using a beta-barrel MP, outer membrane protein F (OmpF), in short-chain polybutadiene-poly(ethylene oxide) (PB-PEO) membranes. Crystals grown in a magnetic field were up to 5 times larger than conventionally grown crystals, and a signal-to-noise (SNR) analysis of diffraction peaks in Fourier transforms of specimens imaged by negative-stain electron microscopy (EM) and cryo-EM showed twice as many high-SNR diffraction peaks, indicating that the magnetic field also improves crystal order. PMID- 26677865 TI - Early Changes in Kidney Distribution under the New Allocation System. AB - The Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18-40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51-60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long term outcomes. PMID- 26677867 TI - Interpolyelectrolyte Complexes of Polycationic Micelles and Linear Polyanions: Structural Stability and Temporal Evolution. AB - The complexation of poly(dimethylaminoethyl methacrylate)-block-poly(styrene) micelles with poly(styrenesulfonate) homopolymers was investigated in aqueous buffer at pH 4.5 as a function of ionic strength. The complexation process was monitored by turbidimetric titration, and the structure and stability of the complexes were assessed by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and small-angle X-ray scattering. When complexes were formed by slow titration of one polyelectrolyte solution into the other, soluble complexes could be formed with either polyelectrolyte in excess as long as the mixture did not pass through the charge-neutral point. The initial complexes exhibited bimodal size distributions by DLS, with one population similar in size to or slightly smaller than the bare micelles, and the other significantly larger. The former correspond to individual micelles with complexed polyelectrolytes leading to a contracted corona; the latter reflect multimicelle aggregates that were directly observed by cryoTEM. At low ionic strength (e.g., 10 mM), these aggregates were stable on weeks-to-months time scales, but at high ionic strength (e.g., 500 mM), the aggregates rapidly annealed toward structures whose size and solubility depended on which polyelectrolyte was present in excess. These results are discussed in terms of the kinetics and thermodynamics of the polyelectrolyte complexation process and allow a detailed description of the interplay between kinetic and thermodynamic factors in this system. This work will inform design of polyelectrolyte complexes with tunable structure and stability for future applications. PMID- 26677868 TI - Stimulus Response of Au-NPs@GMP-Tb Core-Shell Nanoparticles: Toward Colorimetric and Fluorescent Dual-Mode Sensing of Alkaline Phosphatase Activity in Algal Blooms of a Freshwater Lake. AB - In this study, we demonstrate a colorimetric and fluorescent dual-mode method for alkaline phosphatase activity (APA) sensing in freshwater lake with stimuli responsive gold nanoparticles@terbium-guanosine monophosphate (Au-NPs@GMP-Tb) core-shell nanoparticles. Initially, the core-shell nanoparticles were fabricated based on Au-NPs decorated with a fluorescent GMP-Tb shell. Upon being excited at 290 nm, the as-formed Au-NPs@GMP-Tb core-shell nanoparticles emit green fluorescence, and the decorated GMP-Tb shell causes the aggregation of Au-NPs. However, the addition of ALP destroys GMP-Tb shell, resulting in the release of Au-NPs from the shell into the solvent. As a consequence, the aggregated Au-NPs solubilizes with the changes in the UV-vis spectrum of the dispersion, and in the meantime, the fluorescence of GMP-Tb shell turns off, which constitutes a new mechanism for colorimetric and fluorescent dual-mode sensing of APA. With the method developed here, we could monitor the dynamic change of APA during an algal bloom of a freshwater lake, both by the naked eye and further confirmed by fluorometric determination. This study not only offers a new method for on-site visible detection of APA but also provides a strategy for dual-mode sensing mechanisms by the rational design of the excellent optical properties of Au-NPs and the adaptive inclusion properties of the luminescent infinite coordination polymers. PMID- 26677870 TI - Mechanistic Insights into Taxadiene Epoxidation by Taxadiene-5alpha-Hydroxylase. AB - The anticancer molecule taxol (Paclitaxel) stands as one of the most medically and economically important natural products. However, despite decades of extensive study, its biosynthesis remains poorly understood. Unpredictable behavior of the first oxygenation enzyme, taxadiene-5alpha-hydroxylase, which produces a range of undesired products, currently stands as a key bottleneck to improved taxol production. We herein present chemical and biological evidence of an unreported epoxidase activity of taxadiene-5alpha-hydroxylase that puts into question the previously proposed radical-rebound mechanism. We demonstrate that the poor selectivity of taxadiene-5alpha-hydroxylase arises from nonselective degradation of an epoxide intermediate produced via a selective oxidation step, rather than from promiscuous oxidation, as previously proposed. We support these conclusions by demonstrating variable enzyme behavior in differing hosts and conditions, similarity of products and product ratios generated from chemical epoxidation, and taxadiene-5alpha-hydroxylase, and differing enzymatic activity on alternative taxadiene isomers. Additionally, we use directed mutagenesis to describe the oxidizing species of the P450, demonstrate that further in vivo functionalization of oxidized taxadiene is unable to improve selectivity of the oxidation, and show that multiple products are produced in the Taxus cuspidata and are not simply an artifact of heterologous expression. Our results highlight an important, and previously unknown, obstacle to improved taxol production. We further offer insights to overcome the challenges posed by an epoxide-mediated reaction, which sets the basis for further engineering of taxol biosynthesis. PMID- 26677869 TI - A novel antimetabolite: TAS-102 for metastatic colorectal cancer. AB - TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory metastatic colorectal cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in colorectal cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies. PMID- 26677871 TI - Oxidization without substrate unfolding triggers proteolysis of the peroxide sensor, PerR. AB - Peroxide operon regulator (PerR) is a broadly conserved hydrogen peroxide sensor in bacteria, and oxidation of PerR at its regulatory metal-binding site is considered irreversible. Here, we tested whether this oxidation specifically targets PerR for proteolysis. We find that oxidizing conditions stimulate PerR degradation in vivo, and LonA is the principal AAA+ (ATPases associated with diverse cellular activities) protease that degrades PerR. Degradation of PerR by LonA is recapitulated in vitro, and biochemical dissection of this degradation reveals that the presence of regulatory metal and PerR-binding DNA dramatically extends the half-life of the protein. We identified a LonA-recognition site critical for oxidation-controlled PerR turnover. Key residues for LonA interaction are exposed to solvent in PerR lacking metal, but are buried in the metal-bound form. Furthermore, one residue critical for Lon recognition is also essential for specific DNA-binding by PerR, thus explaining how both the metal and DNA ligands prevent PerR degradation. This ligand-controlled allosteric mechanism for protease recognition provides a compelling explanation for how the oxidation-induced conformational change in PerR triggers degradation. Interestingly, the critical residues recognized by LonA and exposed by oxidation do not function as a degron, because they are not sufficient to convert a nonsubstrate protein into a LonA substrate. Rather, these residues are a conformation-discriminator sequence, which must work together with other residues in PerR to evoke efficient degradation. This mechanism provides a useful example of how other proteins with only mild or localized oxidative damage can be targeted for degradation without the need for extensive oxidation-dependent protein denaturation. PMID- 26677872 TI - Long-distance wood procurement and the Chaco florescence. PMID- 26677874 TI - Autoinflammation and autoimmunity in systemic juvenile idiopathic arthritis. PMID- 26677873 TI - Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. AB - Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely on macroautophagy for growth and survival, suggesting a potential therapeutic approach of using autophagy inhibitors based on genetic stratification. In this study, we evaluated whether KRAS mutation status can predict the efficacy to macroautophagy inhibition. By profiling 47 cell lines with pharmacological and genetic loss-of-function tools, we were unable to confirm that KRAS-driven tumor lines require macroautophagy for growth. Deletion of autophagy-related 7 (ATG7) by genome editing completely blocked macroautophagy in several tumor lines with oncogenic mutations in KRAS but did not inhibit cell proliferation in vitro or tumorigenesis in vivo. Furthermore, ATG7 knockout did not sensitize cells to irradiation or to several anticancer agents tested. Interestingly, ATG7-deficient and -proficient cells were equally sensitive to the antiproliferative effect of chloroquine, a lysosomotropic agent often used as a pharmacological tool to evaluate the response to macroautophagy inhibition. Moreover, both cell types manifested synergistic growth inhibition when treated with chloroquine plus the tyrosine kinase inhibitors erlotinib or sunitinib, suggesting that the antiproliferative effects of chloroquine are independent of its suppressive actions on autophagy. PMID- 26677876 TI - Risk of venous thrombo-embolic events in pregnant patients with cancer. AB - OBJECTIVE: Venous thromboembolism (VTE) is one of the leading causes of pregnancy associated death in the Western world. Cancer is a known risk factor for thrombosis outside of pregnancy. The objective of this study is to evaluate the effect of cancer on the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnancy. METHODS: We conducted a retrospective population-based cohort study using the Health Care Cost and Utilization Project database from 2003 to 2011. Risk of developing DVT, PE and VTE among pregnant patients with the 10 most prevalent malignancies was measured using unconditional logistic regression analysis. RESULTS: A total of 2826 women were identified with underlying malignancies, among our study cohort of 7 917 453 women. Risk of VTE was increased among pregnant patients with cervical cancer (OR 8.64, 95% CI (2.15 34.79)), ovarian cancer (OR 10.35, 95% CI (1.44-74.19)), Hodgkin's disease (OR 7.87, 95% CI (2.94-21.05)) and myeloid leukemia (OR 20.75, 95% CI (6.61-65.12)). There was no increased risk of VTE among women with brain cancer, thyroid cancer, melanoma and lymphoid leukemia. CONCLUSION: Many cancers may increase risk of VTE in pregnancy. Appropriate thromboprophylaxis should be considered in some of these women, particularly those with hematological malignancies and gynecologic cancers. PMID- 26677875 TI - Stage-specific embryonic antigen-3 (SSEA-3) and beta3GalT5 are cancer specific and significant markers for breast cancer stem cells. AB - The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding beta-1,3 galactosyltransferase 5 (beta3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine. PMID- 26677877 TI - The complete mitochondrial genome of Hequ horse. AB - The complete mitochondrial genome of Hequ horse was determined in this study. The mitogenome is 16 656 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a D-loop region. The overall base composition of the H-strand is 32.20% for A, 28.55% for C, 13.38% for G and 25.86% for T. Tree constructed using MEGA 6 with Maximum-likelihood (ML) methods demonstrated that Hequ horse was clustered in subfamily Equidae. PMID- 26677879 TI - Identification and Characterization of an Insulin-Like Receptor Involved in Crustacean Reproduction. AB - Sexual differentiation and maintenance of masculinity in crustaceans has been suggested as being regulated by a single androgenic gland (AG) insulin-like peptide (IAG). However, downstream elements involved in the signaling cascade remain unknown. Here we identified and characterized a gene encoding an insulin like receptor in the prawn Macrobrachium rosenbergii (Mr-IR), the first such gene detected in a decapod crustacean. In mining for IRs and other insulin signaling related genes, we constructed a comprehensive M. rosenbergii transcriptomic library from multiple sources. In parallel we sequenced the complete Mr-IR cDNA, confirmed in the wide transcriptomic library. Mr-IR expression was detected in most tissues in both males and females, including the AG and gonads. To study Mr IR function, we performed long-term RNA interference (RNAi) silencing in young male prawns. Although having no effect on growth, Mr-IR silencing advanced the appearance of a male-specific secondary trait. The most noted effects of Mr-IR silencing were hypertrophy of the AG and the associated increased production of Mr-IAG, with an unusual abundance of immature sperm cells being seen in the distal sperm duct. A ligand blot assay using de novo recombinant Mr-IAG confirmed the existence of a ligand-receptor interaction. Whereas these results suggest a role for Mr-IR in the regulation of the AG, we did not see any sexual shift after silencing of Mr-IR, as occurred when the ligand-encoding Mr-IAG gene was silenced. This suggests that sexual differentiation in crustaceans involve more than a single Mr-IAG receptor, emphasizing the complexity of sexual differentiation and maintenance. PMID- 26677878 TI - Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia. AB - A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate. In these studies, chromatin immunoprecipitation followed by DNA sequencing in androgen dependent LNCaP prostate cancer cells demonstrated that 64.3% of NFIB binding sites are associated with AR and FOXA1 binding sites. Interrogation of published data revealed that genes associated with NFIB binding sites are predominantly induced after dihydrotestosterone treatment of LNCaP cells, whereas NFIB knockdown studies demonstrated that loss of NFIB drives increased AR expression and superinduction of a subset of AR target genes. Notably, genes bound by NFIB only are associated with cell division and cell cycle. To define the role of NFIB in vivo, mouse Nfib knockout prostatic tissue was rescued via renal capsule engraftment. Loss of Nfib expression resulted in prostatic hyperplasia, which did not resolve in response to castration, and an expansion of an intermediate cell population in a small subset of grafts. In human benign prostatic hyperplasia, luminal NFIB loss correlated with more severe disease. Finally, some areas of intermediate cell expansion were also associated with NFIB loss. Taken together, these results show a fundamental role for NFIB as a coregulator of AR action in the prostate and in controlling prostatic hyperplasia. PMID- 26677881 TI - Molecular Plasticity of Male and Female Murine Gonadotropes Revealed by mRNA Sequencing. AB - Gonadotropes in the anterior pituitary gland are of particular importance within the hypothalamic-pituitary-gonadal axis because they provide a means of communication and thus a functional link between the brain and the gonads. Recent results indicate that female gonadotropes may be organized in the form of a network that shows plasticity and adapts to the altered endocrine conditions of different physiological states. However, little is known about functional changes on the molecular level within gonadotropes during these different conditions. In this study we capitalize on a binary genetic strategy in order to fluorescently label murine gonadotrope cells. Using this mouse model allows to produce an enriched gonadotrope population using fluorescence activated cell sorting to perform mRNA sequencing. By using this strategy, we analyze and compare the expression profile of murine gonadotropes in different genders and developmental and hormonal stages. We find that gonadotropes taken from juvenile males and females, from cycling females at diestrus and at proestrus, from lactating females, and from adult males each have unique gene expression patterns with approximately 100 to approximately 500 genes expressed only in one particular stage. We also demonstrate extensive gene-expression profile changes with up to approximately 2200 differentially expressed genes when comparing female and male development, juveniles and adults, and cycling females. Differentially expressed genes were significantly enriched in the GnRH signaling, calcium signaling, and MAPK signaling pathways by Kyoto Encyclopedia of Genes and Genomes analysis. Our data provide an unprecedented molecular view of the primary gonadotropes and reveal a high degree of molecular plasticity within the gonadotrope population. PMID- 26677882 TI - Neonatal morbidities and need for intervention in twins and singletons born at 34 35 weeks of gestation. AB - OBJECTIVE: To compare indications for delivery and neonatal morbidities between twins and singletons born between 34 and 35 weeks of gestation. STUDY DESIGN: A prospective observational study was performed in which all infants born between January and August 2008, at Sheba Medical Center at 34 0/7-35 6/7 weeks of gestational age were included. Indications for delivery, infants' morbidities and medical interventions were documented. Twins and singletons were compared for antenatal maternal characteristics, risks of short-term neonatal complications and interventions. RESULTS: One hundred and seventy-three mothers and 229 neonates (114 twins and 115 singletons) were included. Background maternal characteristics as well as the use of antenatal steroids and MgSO4 were similar between the groups. Only 44% of all deliveries were spontaneous, while the rest were indicated deliveries. Twins were born lighter and 31.9% of them were SGA. Nevertheless, singletons were significantly more likely to receive medical interventions such as prolonged oxygen use (>1 day) and phototherapy. All late preterm infants (n=5) needing surfactant administration were singletons. Overall, the risk of needing any medical intervention was significantly higher for singletons compared with twins (OR 1.8, 95% CI 1.02-3.2). CONCLUSIONS: A significant proportion of late preterm births is iatrogenic. Twins and singletons are dissimilar with regards to risks of short-term complications. Despite being born smaller and more SGA, twins are at lower risk of requiring medical intervention in the immediate neonatal period compared with singletons. PMID- 26677883 TI - Genetic low nephron number hypertension is associated with altered expression of key components of the renin-angiotensin system during nephrogenesis. AB - AIM: This study investigates key components of the renin-angiotensin system (RAS) which play a central role in nephrogenesis and possibly in fetal programming of arterial hypertension in adult life. METHODS: We compared a genetic rat model with inborn nephron deficit, the Munich Wistar Fromter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postnatal day 7 (D7). RESULTS: At E19 renal mRNA of angiotensin II type 1a (AT1a) (-50%, P<0.05) and type 1b (AT1b) (-55%, P<0.05) receptors were significantly decreased and renal mRNA expression of angiotensin II type 2 (AT2) receptor was fivefold increased in MWF (n=8) as compared to Wistar rats (n=8). At D7 renal mRNA expression of AT1a (-42%, P<0.05) remained lower in MWF (n=8) as compared to Wistar (n=7). Renal mRNA expression of AT2 (-30%, P>0.05) decreased in MWF (n=8) to about the level of the Wistar control (n=6). CONCLUSIONS: Altered fetal expression of key molecules of the renin-angiotensin system in MWF indicates a possible role in genetic low nephron number hypertension. PMID- 26677884 TI - Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients. AB - BACKGROUND: The aim of this study was to compare resistivity index (RI) in type 1 diabetic patients and normal controls and to evaluate whether high RI is associated with different biomarkers of diabetic nephropathy (DN) as early detection of DN offers the best chance of delaying or possibly preventing progression to end-stage renal disease. METHODS: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of glycosylated hemoglobin, lipid profile and urine samples were taken for assessment of albumin/creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L FABP) and kidney injury molecule-1 (Kim-1). Forty-five diabetic patients and 30 controls had a renal Doppler ultrasonography. t-Test or Mann Whitney U-test for independent variables, Pearson's or Spearman correlation analysis were used. RESULTS: The mean age of diabetic patients was 16.3+/-1.5 years, and mean duration of diabetes was 9.4+/-2.9 years. RI, albumin/creatinine ratio, NGAL, Kim 1 and L-FABP were significantly higher in diabetics than in controls. RI, NGAL, Kim-1, and L-FABP were significantly higher in microalbuminuric compared to normoalbuminuric diabetics. In normoalbuminuric diabetics, RI, NGAL, Kim-1 and L FABP were significantly higher compared to controls. The study revealed significant positive correlation between the RI in diabetics and both KIM-1 and albumin/creatinine ratio. CONCLUSIONS: Increased RI and renal biomarkers in diabetics are early sensitive specific markers of DN, even preceded the development of microalbuminuria, denoting that they can be used as an early and sensitive markers for early detection of DN. PMID- 26677880 TI - Excess Maternal Fructose Consumption Increases Fetal Loss and Impairs Endometrial Decidualization in Mice. AB - The most significant increase in metabolic syndrome over the previous decade occurred in women of reproductive age, which is alarming given that metabolic syndrome is associated with reproductive problems including subfertility and early pregnancy loss. Individuals with metabolic syndrome often consume excess fructose, and several studies have concluded that excess fructose intake contributes to metabolic syndrome development. Here, we examined the effects of increased fructose consumption on pregnancy outcomes in mice. Female mice fed a high-fructose diet (HFrD) for 6 weeks developed glucose intolerance and mild fatty liver but did not develop other prominent features of metabolic syndrome such as weight gain, hyperglycemia, and hyperinsulinemia. Upon mating, HFrD exposed mice had lower pregnancy rates and smaller litters at midgestation than chow-fed controls. To explain this phenomenon, we performed artificial decidualization experiments and found that HFrD consumption impaired decidualization. This appeared to be due to decreased circulating progesterone as exogenous progesterone administration rescued decidualization. Furthermore, HFrD intake was associated with decreased bone morphogenetic protein 2 expression and signaling, both of which were restored by exogenous progesterone. Finally, expression of forkhead box O1 and superoxide dismutase 2 [Mn] proteins were decreased in the uteri of HFrD-fed mice, suggesting that HFrD consumption promotes a prooxidative environment in the endometrium. In summary, these data suggest that excess fructose consumption impairs murine fertility by decreasing steroid hormone synthesis and promoting an adverse uterine environment. PMID- 26677885 TI - An adolescent girl referred with Cushing syndrome--does she or does she not have the syndrome? AB - Cushing syndrome and lipodystrophy syndromes share similar clinical features. This report describes an adolescent girl with newly diagnosed familial partial lipodystrophy type 2 (FPLD2) who was initially referred for Cushing syndrome. The type of abnormal fat deposition syndrome can be elucidated by careful clinical examination. FPLD2 can lead to type 2 diabetes mellitus and early cardiovascular events. Partial lipodystrophy presenting for the first time in adolescence can be mistaken for corticosteroid excess. Early diagnosis and preventative management of cardiovascular risk factors are crucial. PMID- 26677886 TI - Analytical interference by monoclonal immunoglobulins on the direct bilirubin AU Beckman Coulter assay: the benefit of unsuspected diagnosis from spurious results. AB - BACKGROUND: Monoclonal (M) components can interfere with the direct bilirubin (D Bil) assay on the AU Beckman Coulter instrumentation and produce spurious results, such as D-Bil values greater than total bilirubin (T-Bil) or very low/negative D-Bil values. If properly detected, this interference may uncover undiagnosed patients with monoclonal gammopathy (MG). METHODS: We investigated the interference rate on the D-Bil AU assay in serum samples known to contain M proteins along with their isotype and described the protocol set up in our laboratory to help with the diagnosis of MG based on D-Bil spurious results as first indication. RESULTS: During a period of 4 years, 15.4% (345 of 2235) of serum samples containing M immunoglobulins produced erroneous D-Bil results, although no clear relationship between the magnitude or isotype of the M component and interference could be found. In total 22 new patients were diagnosed with MG based on the analytical artefact with the D-Bil as first indication. CONCLUSIONS: The D-Bil interference from MG on the Beckman AU analysers needs to be made known to laboratories in order to prevent clinical confusion and/or additional workup to explain the origin of anomalous results. Although this information may not add to the management of existing patients with serum paraproteins, it can benefit patients that have not been diagnosed with MG by triggering follow up testing to determine if M components are present. PMID- 26677887 TI - Dopamine concentration in blood platelets is elevated in patients with head and neck paragangliomas. AB - BACKGROUND: Plasma 3-methoxytyramine (3-MT), a metabolite of dopamine, is elevated in up to 28% of patients with head and neck paragangliomas (HNPGLs). As free dopamine is incorporated in circulating platelets, we determined dopamine concentration in platelets in patients with a HNPGL. METHODS: A single center cohort study was performed between 2012 and 2014. Thirty-six patients with a HNPGL were compared to healthy controls (68 for dopamine in platelets and 120 for plasma 3-MT). RESULTS: Dopamine concentration in platelets was elevated in HNPGL patients compared to healthy controls (median [interquartile ranges] 0.48 [0.32 0.82] pmol/109 platelets vs. 0.31 [0.24-0.47] pmol/109 platelets; p<0.05), whereas plasma 3-MT concentration did not differ between both groups (0.06 [0.06 0.08] nmol/L vs. 0.06 [0.06-0.06] nmol/L; p=0.119). Based on 68 healthy controls, the reference interval for dopamine concentration in platelets was 0.12-0.97 pmol/109 platelets. Six (16.7%) patients with a HNPGL demonstrated an increased dopamine concentration in platelets compared to three (8.3%) patients with an increased plasma 3-MT level (p=0.053). The sensitivity and specificity were 16.7% and 98.5% for platelet dopamine and 8.3% and 97.5% for plasma 3-MT concentration (p=0.37). CONCLUSIONS: Dopamine concentration in platelets is elevated in patients with a HNPGL compared to healthy subjects, and may be a novel biomarker for dopamine producing paraganglioma. PMID- 26677888 TI - EQA-derived metrics to assess overall instrument performance. PMID- 26677889 TI - Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint. AB - Monoclonal gammopathies are characterised by the production of a monoclonal immunoglobulin or free light chains by an abnormal plasma cell or B-cell clone and may indicate malignancy or a precursor (MGUS). There is currently no consensus on the initial test or combination of tests to be performed in suspected monoclonal gammopathies but serum protein electrophoresis and urine protein electrophoresis are commonly requested as initial investigations. If abnormal, immunofixation electrophoresis is then performed to confirm the presence of paraprotein and to determine its heavy and light chain type. Recently, some groups have developed simplified "screening" IFE methods for use in parallel to SPEP for the detection monoclonal gammopathies. We argue here that screening IFE may be of benefit in clinical laboratories using SPEP with poor resolution in the beta-region, assisting in the detection of mainly IgA paraprotein, but may be of less benefit in laboratories utilising higher resolution gels. Further it may increase the detection of trace bands of questionable clinical significance, representing transient phenomena in infectious and auto-immune conditions or very low risk MGUS. The increased detection of these bands using screening IFE would require further patient follow up, possibly causing unnecessary patient anxiety and additional follow up healthcare costs. PMID- 26677890 TI - A patient with AL amyloidosis with negative free light chain results. AB - The detection and quantification of amyloidogenic monoclonal light chains are necessary for the diagnosis and evaluation of response to treatment in AL amyloidosis. However, the amyloid clone is often small and difficult to detect. We report the case of a 68-year-old man who was referred to our Center in April 2013 after syncope and the identification of left ventricular hypertrophy at echocardiography, suspected for amyloidosis. A commercial agarose gel electrophoresis immunofixation (IFE) did not reveal monoclonal components in serum and urine. The kappa serum free light chain (FLC) concentration was 21.5 mg/L, lambda 33 mg/L (kappa/lambda ratio 0.65), NT-proBNP 9074 ng/L (u.r.l. <332 ng/L) and an echocardiogram confirmed characteristic features of amyloidosis. The abdominal fat aspiration was positive and the amyloid typing by immune-electron microscopy revealed lambda light chains deposits. A high-resolution (hr) IFE of serum and urine showed a faint monoclonal lambda component in the urine. A bone marrow biopsy showed 8% plasma cells (BMPC) and a kappa/lambda light-chain restriction with lambda light chain on immunofluorescence. The diagnosis of AL (lambda) amyloidosis with cardiac involvement was made. In May 2013, patient was started on cyclophosphamide, bortezomib and dexamethasone. After six cycles, serum and urine hr-IFE were negative, the bone marrow biopsy showed 3% BMPC without light chain restriction by immunofluorescence, and a decrease of NT proBNP was observed (5802 ng/L).Thus, treatment was discontinued. In this patient the amyloid clone could be detected only by in house hr-IFE of urine and bone marrow examination. The detection of the small dangerous amyloidogenic clone should be pursued with a combination of high-sensitivity techniques, including assessment of BMPC clonality. Studies of novel tools, such as mass spectrometry on serum and next-generation flow cytometry analysis of the bone marrow, for detecting plasma cell clones in AL amyloidosis and other monoclonal light chain related disorders are warranted. PMID- 26677891 TI - A diagnostic algorithm for the detection of inhibitors against coagulation Factor V. PMID- 26677892 TI - Comparison of the clinical utility of the Elia CTD Screen to indirect immunofluorescence on Hep-2 cells. AB - BACKGROUND: We compared the Elia CTD Screen (ECS), a fluoroenzymeimmunoassay incorporating 17 human antinuclear antigens (ANA), with indirect immunofluorescence (IIF) on Hep-2 cells in order to determine the clinical utility of the ECS in additon to or without IIF. METHODS: We examined 1708 consecutive serum samples submitted for ANA testing using the ECS and IIF in parallel. Positive screen results were further examined by quantitative fluoroenzymeimmunoassays and/or immunoblots for antibody identification. The medical records were evaluated for systemic rheumatic disorders. RESULTS: Concordance between ECS and IIF was observed in 1344 (78.8%) samples. ECS had a better detection rate for anti-dsDNA, -SSA/Ro, -SSB/La, -U1RNP and -Jo-1 antibodies, whereas IIF was superior in the detection of anti-CENP-B antibodies as well as anti-histone, -nucleosome and -Pl-12 antibodies, which are not included in the ECS antigen panel. ECS had a 100% sensitivity for Sjogren's syndrome, systemic sclerosis and Sharp syndrome. The sensitivity for Sjogren's syndrome was slightly higher for ESC than for IIF (94%). IIF had a higher diagnostic sensitivity for systemic lupus erythematosus, indeterminated connective tissue disease, Raynaud's syndrome and limited scleroderma, compared to ESC (100% vs. 80%, 100 vs. 75%, 89 vs. 57%, 100 vs. 88.9%). CONCLUSIONS: Our results suggest that the ECS represents an appropriate diagnostic tool for ANA screening. However, since some antigens are not incorporated in the ECS panel, and some ANA can also be missed by IIF, sequential or parallel screening with ECS and IIF may be reasonable when the clinical suspicion for connective tissue disease is high. PMID- 26677893 TI - Differences in analytical and biological results between older and newer lots of a widely used irisin immunoassay question the validity of previous studies. PMID- 26677894 TI - Practice implications and recommendations for managing codeine misuse and dependence. AB - Codeine, a weak opiate, requires increased pharmacovigilance relating to availability, heterogeneous nature of misuse, dependence and associated harm. A scoping review of literature on codeine was conducted using Arksey & O'Malley's framework (1). Databases searched included PubMed, EBSCO Host, Science Direct, EMBASE, PsycINFO, Cochrane library and Medline from 1994 to 2014. Follow-up search strategies involved hand searching and searching of pharmaceutical, health, medical and drug related websites. Initial zscreening identified 3,105 articles with 475 meeting the inclusion criteria. Eight broad categories organised the literature, data charting and qualitative synthesis. This paper presents implications for practice and makes recommendations to address these issues. Themes identified relate to raising public and practitioner awareness, risk management, dispensing practices and monitoring and surveillance of codeine. Evidence to inform law enforcement, drug surveillance, public health initiatives, harm reduction approaches, pharmacy, clinical and treatment practices is warranted. PMID- 26677895 TI - Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics. AB - This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for pre- and post-compression characteristics. The prepared OD-mini tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use. PMID- 26677896 TI - Influence of pH modifiers on the dissolution and stability of hydrochlorothiazide in the bi- and three-layer tablets. AB - During the past few years, the studies of bi- and multi-layered tablets increased due to the consumption of several different drugs per day by a patient and requests for appropriate patient compliance. The demographic shift toward older population increases the use of combination therapy as polypharmacy. Hydrochlorothiazide (HCTZ), as a model drug, is most commonly used in the treatment of hypertension, congestive heart failure and as a diuretic. The aim of the present study is to investigate the effect of the local environment on dissolution and stability behaviour of HCTZ in fixed multilayered tablet combinations, which are commonly used in polypharmacy. For this purposes, three different systems were introduced: (i) two conventional tablets (HCTZ and pH modifying placebo), (ii) 2-layer tablets (HCTZ, pH modifying placebo) and (iii) 3 layer tablets (HCTZ, barrier and pH modifying placebo). Disintegration of tablets, dissolution of HCTZ from tablets and HCTZ related substances were monitored for all systems. Results showed that there was a significant difference between dissolution profiles of the conventional two-tablet system (HCTZ tablet and pH modifying tablet) and the 2-layer and 3-layer tablets, which include the pH modifying layer. In the case of the conventional two-tablets system, 85 % of HCTZ was dissolved in less than 15 minutes. The dissolution profiles of HCTZ from 2-layered and 3-layered tablets showed a decrease in the dissolution rate. In addition, during the stability studies, it has been confirmed that the typical degradation product of HCTZ is formed, impurity B (4-amino-6-chloro-1,3 benzenedisulfonamide), which implies formation of formaldehyde as hydrolytic impurity not reported in the Ph. Eur. (16). Both impurities are particularly raised in 2-layered tablets with alkaline and neutral placebo layers. Stability of HCTZ was improved in the case of the 3-layer tablet, where the intermediate separation layer of glycerol monostearate was present. It is presumed that the HCTZ dissolution rate was decreased due to formation of non-soluble substances as a result of HCTZ degradation in the presence of alkaline layer. PMID- 26677897 TI - Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives. AB - Reaction of 6-amino-3-methyl-4-(substituted phenyl)-1,4- dihydropyrano[2,3 c]pyrazole-5-carbonitrile (1) with triethylorthoformate followed by treatment with hydrazine hydrate, formic acid, acetic acid, phenylisocyanate, ammonium thiocyanate and formamide afforded the corresponding pyranopyrimidine derivatives 2-6. Cyclocondensation of 1 with cyclohexanone afforded pyrazolopyranoquinoline 7. One-pot process of diazotation and de-diazochlorination of 1 afforded pyrazolopyranotriazine derivative 8, which upon treatment with secondary amines afforded 9 and 10a- c. Condensation of 2 with aromatic aldehyde gave the corresponding Schiff bases 11a,b, the oxidative cyclization of the hydrazone with appropriate oxidant afforded 11-(4- fluorophenyl))- 2-(4-substituted phenyl)-10 methyl-8,11-dihydropyrazolo-[ 4',3':5,6]pyrano[3,2-e][1,2,4]triazolo[1,5 c]pyrimidines (12a,b). Structures of the synthesized compounds were confirmed by spectral data and elemental analysis. All synthesized compounds were evaluated for antibacterial and antifungal activities compared to norfloxacin and fluconazole as standard drugs. Compounds 9, 10c, 12a and 15 were found to be the most potent antibacterial agents, with activity equal to that of norfloxacin. On the other hand, compound 5 exhibited higher antifungal activity compared to fluconazole. PMID- 26677899 TI - Deciphering nifedipine in vivo delivery from modified release dosage forms: Identification of food effect. AB - With the increased reliance on in vitro dissolution testing as an indicator of in vivo drug behavior and the trend towards the in silico modeling of dosage form performance, the need for bioperformance dissolution methodology development has been enhanced. Determination of the in vivo drug delivery profile is essential for the bioperformance dissolution test development and in vitro/in vivo correlation modeling, as well as the understanding of absorption mechanisms. The aim of this study was to compare different methods in terms of their usefulness and applicability in deciphering in vivo delivery of nifedipine administered in modified release dosage forms. A detailed survey of publications on nifedipine pharmacokinetics was done and used to identify the magnitude of food effect. In vitro dissolution testing was performed under various experimental conditions. Obtained results indicate the potential for using the developed in silico model coupled with discriminative in vitro dissolution data for identification of the in vivo drug product behavior. PMID- 26677898 TI - Nitrones: not only extraordinary spin traps, but also good nitric oxide sources in vivo. AB - Free radicals are involved in the development of reperfusion injuries. Using a spin trap, the intensity of such lesions can be reduced. Nitrones (effective in vivo spin traps) were tried in this work as in vivo nitric oxide donors. Nitrite and nitrate concentration values (rabbit blood) were used as biomarkers of nitric oxide production. Most nitrones did not increase plasma concentrations of nitrite and nitrate; on the contrary, reduced plasma concentrations of these indicators were noted. However, glyoxal isopropyldinitrone, in a dose of 50 mg kg-1, was highly effective in increasing nitric oxide production. At the same time, nitrones do not react with hepatic homogenates, proving that the release of nitric oxide takes place in the tissues and is not related to hepatic metabolism. Before using nitrones in vivo, they were tested in vitro for the ability to release nitric oxide following a reaction with the hydroxyl radical. PMID- 26677900 TI - Modulation of brain glutamate dehydrogenase as a tool for controlling seizures. AB - Glutamate (Glu) is a major excitatory neurotransmitter involved in epilepsy. Glu is synthesized by glutamate dehydrogenase (GDH, E.C. 1.4.1.3) and dysfunction of the enzymatic activity of GDH is associated with brain pathologies. The main goal of this work is to establish the role of GDH in the effects of antiepileptic drugs (AEDs) such as valproate (VALP), diazepam (DIAZ) and diphenylhydantoin (DPH) and its repercussions on oxygen consumption. Oxidative deamination of Glu and reductive amination of alphaketoglutarate (alphaK) in mice brain were investigated. Our results show that AEDs decrease GDH activity and oxygen consumption in vitro. In ex vivo experiments, AEDs increased GDH activity but decreased oxygen consumption during Glu oxidative deamination. VALP and DPH reversed the increase in reductive amination of alphaK caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreased oxygen consumption. GDH represents an important regulation point of neuronal excitability, and modulation of its activity represents a potential target for metabolic treatment of epilepsy and for the development of new AEDs. PMID- 26677901 TI - Preparation and investigation of mefenamic acid - polyethylene glycol - sucrose ester solid dispersions. AB - Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives. PMID- 26677902 TI - Induction of cell cycle arrest via the p21, p27-cyclin E,A/Cdk2 pathway in SMMC 7721 hepatoma cells by clioquinol. AB - Clioquinol has been shown to have anticancer activity in several carcinoma cells. In this study, we preliminarily examined the effect of clioquinol in human SMMC 7721 hepatoma and QSG-7701 normal hepatic cells. Our results indicated that clioquinol did not significantly affect survival of QSG-7701 cells, whereas it reduced cell viability in a concentration- and time-dependent manner in SMMC-7721 cells. Clioquinol did not trigger autophagy and apoptosis, while it induced cell cycle arrest in the S-phase in SMMC- 7721 cells. Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment with clioquinol. The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27-cyclin E,A/Cdk2 pathway. This suggests that clioquinol may have a therapeutic potential as an anticancer drug for certain malignances. PMID- 26677903 TI - Fractionation and evaluation of proteins in roots of Echinacea purpurea (L.) Moench. AB - Echinacea purpurea (L.) Moench, a member of the Asteraceae family, is a plant rich in flavonoids, essential oils, phenolic compounds, saponins, polysaccharides and glycoproteins. The aim of the study was to evaluate the protein content in dried roots of Echinacea purpurea (L.) Moench after homogenization of roots with liquid nitrogen, extraction in 0.01 mol L-1 phosphate-buffered saline (PBS) and purification followed by fractionation of proteins using gel filtration chromatography. Total concentration of proteins was measured using the Bradford method, and evaluation of the molecular mass of proteins was accomplished by applying the SDS-PAGE gel electrophoresis. The Bradford assay revealed that the highest concentration of proteins in fractions collected after gel filtration chomatography was 4.66-6.07 mg mL-1. Glycoproteins, alkamides and polysaccharides in roots of Echinacea purpurea (L.) Moench are chemical compounds that are responsible for their immunomodulatory properties. However, information about the difference of protein contents in fresh and dried roots of E. purpurea is insufficient. PMID- 26677904 TI - Great migration: epigenetic reprogramming and germ cell-oocyte metamorphosis determine individual ovarian reserve. AB - Emigration is defined as a synchronized movement of germ cells between the yolk sack and genital ridges. The miraculous migration of germ cells resembles the remigration of salmon traveling from one habitat to other. This migration of germ cells is indispensible for the development of new generations. It is not, however, clear why germ cells differentiate during migration but not at the place of origin. In order to escape harmful somatic signals which might disturb the proper establishment of germ cells forced germ cell migration may be necessary. Another reason may be to benefit from the opportunities of new habitats. Therefore, emigration may have powerful effects on the population dynamics of the immigrant germ cells. While some of these cells do reach their target, some others die or reach to wrong targets. Only germ cell precursors with genetically, and structurally powerful can reach their target. Likewise, epigenetic reprogramming in both migratory and post-migratory germ cells is essential for the establishment of totipotency. During this journey some germ cells may sacrifice themselves for the goodness of the others. The number and quality of germ cells reaching the genital ridge may vary depending on the problems encountered during migration. If the aim in germ cell specification is to provide an optimal ovarian reserve for the continuity of the generation, then this cascade of events cannot be only accomplished at the same level for every one but also are manifested by several outcomes. This is significant evidence supporting the possibility of unique individual ovarian reserve. PMID- 26677905 TI - Progestogens in the prevention of miscarriage. AB - Progestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. A recent Cochrane review reported that progestogens were effective for treating threatened miscarriage with no harmful effects on mother or fetus. The results were not statistically different when vaginal progesterone was compared to placebo, (RR=0.47, 95% CI 0.17-1.30), whereas oral progestogen (dydrogesterone) was effective (RR=0.54, CI 0.35-0.84). The review concluded, that the small number of eligible studies, and the small number of the participants, limited the power of the metaanalysis. A later metaanalysis of five randomised controlled trials of threatened miscarriage comprised 660 patients. The results of 335 women who received dydrogesterone were compared to 325 women receiveing either placebo or bed rest. There was a 47% reduction in the odds ratio for miscarriage, (OR=0.47, CI 0.31-0.7). There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women. Recurrent miscarriage affects approximately 1% of women of child bearing age. A metaanalysis of progestational agents shows a 26% increase in the live birth rate. Again, dydrogesterone was associated with a more significant increase in the live birth rate than the other progestogens included in the metaanalysis. PMID- 26677906 TI - In vitro inhibition and enhancement of liver microsomal S-777469 metabolism by long-chain fatty acids and serum albumin: insight into in vitro and in vivo discrepancy of metabolite formation in humans. AB - 1. It was previously demonstrated that 10% of S-777469, a cannabinoid receptor 2 selective agonist, is metabolized to its carboxylic acid metabolite (S-777469 5 carboxylic acid, 5-CA) in humans in vivo, while the formation of 5-CA is extremely low in human cryopreserved hepatocytes and liver microsomes (HLMs). In this study, factors causing the different metabolite formation rates of S-777469 in vitro and in vivo were investigated. 2. Formation of 5-CA and S-777469 5 hydroxymethyl (5-HM), a precursor metabolite of 5-CA, was catalyzed by CYP2C9. Arachidonic acid, alpha-linolenic acid, oleic acid and myristic acid, which have been reported to exist in liver microsomes, inhibited S-777469 oxidation by CYP2C9, but serum albumin enhanced this reactions. 3. The IC50 values of these fatty acids for 5-CA formation from 5-HM were lower than those of 5-HM formation from S-777469. Serum albumin extensively enhanced 5-CA formation from 5-HM in comparison to 5-HM formation from S-777469. 4. CYP2C9 was the enzyme responsible for S-777469 oxidation in human livers. The suppressive effects of several fatty acids and enhancing action of serum albumin in vitro are likely to be the causal factors for the apparently different rates of in vitro and in vivo metabolite formation of S-777469. PMID- 26677907 TI - Postoperative Shifts in Adult Strabismus Patients with Visual Deficits. AB - OBJECTIVE: To evaluate the effects of corrective surgery in adult strabismic patients with visual deficits and the stability of postoperative alignments. METHODS: Retrospective study. Alignment and binocular visual function were evaluated in adult patients with visual deficits (best corrective visual acuity (BCVA) <0.3 in one or both eyes) with at least 6 months postoperative follow-up. The results in these patients were compared to those in patients with normal or nearly normal vision (BCVA >= 0.6 in the worse eye) matched by the type of strabismus, magnitude of deviation, age at the time of corrective surgery, and length of time before final follow-up. RESULTS: Sixty-four patients aged 28.3 +/- 12.0 (17~65) years were included in the visual deficit group, and 64 subjects aged 26.8 +/- 9.4 (17~58) years were included in the matched control group. No significant difference was found in the age or deviation angle between the two groups. The surgery was considered a success in 42 patients (65.6%) in the visual deficit group and 55 patients (86%) in the control group at the last visit (Chi2 = 7.19, p = 0.008). Normal or partially normal stereo acuity was achieved by three patients in the visual deficit group and 29 patients in the control group. An average shift toward exotropia of 7.3 prism diopter (PD) in the visual deficit group and 4.9 PD in the control group was observed between postoperative day 1 and the final visit (t = 2.08, p = 0.04). Of the 22 patients in the visual deficit group that were defined as "not a success," 20 were under-corrected, and two were over-corrected. CONCLUSION: Adults with poor vision experienced positive results from corrective surgery via a postoperative shift toward exotropia. Full correction of deviation and postoperative shift should be considered before surgery. PMID- 26677908 TI - 17beta-estradiol prevents experimentally-induced oxidative damage to membrane lipids and nuclear DNA in porcine ovary. AB - Estrogens, with their principle representative 17beta-estradiol, contribute to the redox state of cells showing both pro- and antioxidative properties. In the ovary, being the main source of estrogens, maintaining balance between the production and detoxification of ROS is crucial. Whereas ovary estrogen concentration is difficult to estimate, its circulating concentration in women may reach the nanomolar level. The aim of the study was to evaluate the effects of 17beta-estradiol on oxidative damage to membrane lipids (lipid peroxidation, LPO) and to nuclear DNA in the porcine ovary under basal conditions and in the presence of Fenton reaction (Fe(2+)+H2O2->Fe(3+)+(*)OH + OH(-)) substrates. Ovary homogenates and DNA were incubated in the presence of 17beta-estradiol (1 mM-1 pM), without/with FeSO4 (30 MUM) + H2O2 (0.5 mM). Malondialdehyde + 4 hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. The concentration of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) (DNA damage index) was measured by HPLC. We observed that 17beta estradiol did not alter the basal level of oxidative damage, but reduced Fe(2+)+H2O2-induced oxidative damage to membrane lipids when >=10 nM and to DNA at concentrations >=1 nM. In the ovary at near physiological concentration, 17beta-estradiol prevents experimentally induced oxidative damage. This suggests that under physiological conditions this hormone may contribute to protecting the ovary against oxidative damage. PMID- 26677909 TI - The human carbonic anhydrase isoenzymes I and II inhibitory effects of some hydroperoxides, alcohols, and acetates. AB - The carbonic anhydrases (CAs, EC 4.2.1.1) represent a superfamily of widespread enzymes, which catalyze a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, a series of hydroperoxides, alcohols, and acetates were tested for the inhibition of the cytosolic hCA I and II isoenzymes. These compounds inhibited both hCA isozymes in the low nanomolar ranges. These compounds were good hCA I inhibitors (Kis in the range of 24.93-97.99 nM) and hCA II inhibitors (Kis in the range of 26.04-68.56 nM) compared to acetazolamide as CA inhibitor (Ki: 34.50 nM for hCA I and Ki: 28.93 nM for hCA II). PMID- 26677910 TI - Peroxisome Proliferator-Activated Receptor gamma Regulates Chronic Alcohol Induced Alveolar Macrophage Dysfunction. AB - Peroxisome proliferator-activated receptor (PPAR) gamma is critical for alveolar macrophage (AM) function. Chronic alcohol abuse causes AM phagocytic dysfunction and susceptibility to respiratory infections by stimulating nicotinamide adenine dinucleotide oxidases (Nox), transforming growth factor-beta1, and oxidative stress in the AM. Because PPARgamma inhibits Nox expression, we hypothesized that alcohol reduces PPARgamma, stimulating AM dysfunction. AMs were examined from: (1) patients with alcoholism or control patients; (2) a mouse model of chronic ethanol consumption; (3) PPARgamma knockout mice; or (4) MH-S cells exposed to ethanol in vitro. Alcohol reduced AM PPARgamma levels and increased Nox1, -2, and -4, transforming growth factor-beta1, oxidative stress, and phagocytic dysfunction. Genetic loss of PPARgamma recapitulated, whereas stimulating PPARgamma activity attenuated alcohol-mediated alterations in gene expression and phagocytic function, supporting the importance of PPARgamma in alcohol-induced AM derangements. Similarly, PPARgamma activation in vivo reduced alcohol-mediated impairments in lung bacterial clearance. Alcohol increased levels of microRNA 130a/-301a, which bind to the PPARgamma 3' untranslated region to reduce PPARgamma expression. MicroRNA-130a/-301a inhibition attenuated alcohol-mediated PPARgamma reductions and derangements in AM gene expression and function. Alcohol induced Toll-like receptor 4 endocytosis was reversed by PPARgamma activation. These findings demonstrate that targeting PPARgamma provides a novel therapeutic approach for mitigating alcohol-induced AM derangements and susceptibility to lung infection. PMID- 26677911 TI - Aquaporins in boar spermatozoa. Part II: detection and localisation of aquaglyceroporin 3. AB - The proteins belonging to the aquaporin family play a fundamental role in water and solute transport across biological membranes. While the presence of these proteins has been extensively studied in somatic cells, their function in mammalian spermatozoa has been studied less. The present study was designed to identify and localise aquaglyceroporin 3 (AQP3) in boar spermatozoa. With this purpose, 29 fresh ejaculates from post-pubertal Pietrain boars were classified into two groups based upon their sperm quality and subsequently evaluated through western blot and immunofluorescence assessments. Western blotting showed the specific signal band of AQP3 at 25 kDa, whereas immunofluorescence assessments allowed us to identify two different AQP3 localisation patterns: (1) spermatozoa presenting a clear labelling located only in the mid-piece and (2) spermatozoa exhibiting a distribution pattern in the head and along the entire tail. The first staining pattern was predominant in all studied ejaculates. Despite individual differences in AQP3 content and localisation between boar ejaculates, these differences were not correlated with sperm quality. In conclusion, although AQP3 is present in boar spermatozoa in two different localisation patterns, neither the AQP3 content nor its localisation have been found to be associated with conventional sperm parameters. PMID- 26677912 TI - The mitogenome of Hydropsyche pellucidula (Hydropsychidae): first gene arrangement in the insect order Trichoptera. AB - We describe the mitochondrial genome of Hydropsyche pellucidula Curtis 1834, which is first described for the suborder Annulipalpia and the first in the order Trichoptera to show a non-canonical gene order. The mitogenome was obtained by de novo assembly of shotgun sequenced total genomic DNA using Illumina Miseq technology, which produced an average coverage of 115* and a minimum coverage of 48*. The mitochondrial genome includes 13 protein-coding genes, 2 rRNAs and 22 tRNAs. The genome is characterized by a rearrangement in the relative position of protein-coding and ribosomal genes. This mitogenome sequence will be useful for studying the family Hydropsychidae, which is commonly used for freshwater pollution biomonitoring. PMID- 26677913 TI - Clinical decision making regarding suicide risk: Effect of patient and clinician age. AB - To ascertain how patient age influences suicide risk assessment, clinicians (N = 262) read an ambiguous vignette about Bill (aged either 39 or 79 years old) and subsequently rated Bill's suicide risk and hospitalization needs. Suicide-risk ratings varied greatly and young clinicians rated Bill's suicide risk and hospitalization needs higher when he was elderly (79 years old); whereas, older clinicians rated Bill's suicide risk and need for hospitalization higher when he was younger (39 years old). The interaction between patient and clinician age may reflect a "similarity" bias, such that clinicians perceive those who are different (i.e., younger or older) to be at elevated risk. PMID- 26677914 TI - Mediators of disability and hope for people with spinal cord injury. AB - PURPOSE: To test potential strength-based mediators of functional disability and hope in adults with spinal cord injury. METHOD: Two hundred and forty-two participants with spinal cord injury were recruited for this study. The mean age of participants was 44.6 years (standard deviation = 13.2), and 66.1% were men. Participants completed a survey containing a demographic questionnaire, as well as measures of functional disability, hope, self-esteem, proactive coping, perceived social support and disability acceptance. Mediation analysis was conducted using a bootstrap test for multiple mediators. RESULTS: Proactive coping, self-esteem and perceived social support significantly mediated the relationship between functional disability and hope, while disability acceptance did not. The combination of mediators resulted in functional disability no longer being a significant predictor of hope. CONCLUSIONS: The strength-based constructs of proactive coping, self-esteem and social support appear effective in predicting hope regardless of severity of spinal cord injury. Functional disability was no longer predictive of hope after controlling for these strength based constructs. Disability acceptance did not significantly add to the mediation model. These results provide further evidence for strength-based interventions in rehabilitation. Implications for Rehabilitation Strength-based constructs of proactive coping, self-esteem and social support are important factors for addressing hope following spinal cord injury, regardless of level of severity. Rehabilitation services providers should focus efforts on supporting clients in the accurate appraisal of predictable stressors and then generate means for addressing them as a form of proactive coping. Rehabilitation services providers must be cautious when addressing self-esteem to focus on perceived competence and learning processes rather than self-esteem directly or through the accomplishment of goals that may not be achieved. Knowing that social supports are related to hope post-spinal cord injury, it is important for rehabilitation services providers to recognize potential social supports early in the rehabilitation process and involve those social supports in the rehabilitation process when possible. PMID- 26677915 TI - Pain control after pediatric surgery: learning from the past to perfect the future. PMID- 26677916 TI - Budesonide/salmeterol in fixed-dose combination for the treatment of asthma. AB - Fixed dose combinations (FDC) of inhaled corticosteroid (ICS) and long-acting beta agonist (LABA) are well established in asthma treatment. The budesonide/salmeterol (B/S) FDC is now about to reach the market. It is provided as powder in hard capsules of two strengths: 120/20MUg and 240/20MUg when expressed as delivered doses, equivalent to 150/25MUg and 300/25MUg when expressed as nominal doses. Its development involved 9 pharmacokinetic (320 subjects), 3 phase II (123 subjects) and 4 phase III (1206 patients with different asthma severity) studies. Delivery is effectuated via low resistance inhaler device, Axahaler(r), generating also fine particles targeting the small airways. B/S safety, assessed in 1401 subjects, did not outline novel concerns specific for this FDC. In conclusion, the B/S dry powder FDC can be used for asthma treatment in adults not adequately controlled on ICS alone, or to maintain control of ICS/LABA treated patients, in whom switching to alternative FDC is indicated. PMID- 26677930 TI - Diabetes Management and Cardiovascular Risk: Are SGLT-2 Inhibitors the Safest? AB - For five millennia, diabetes management has focused on controlling blood sugar and efforts to minimize the complications of this disease have depended on normalizing glucose. Since the 1970's, however, a growing awareness of the adverse effect of hypoglycemic agents on cardiac health has led to an increasing focus on the effect of diabetes management on cardiac risk. This was brought into focus in the early years of this century with issues around rosiglitazone and resulted in the United States Food and Drug Administration, mandating that new drug applications for diabetes include documentation of no adverse effect on cardiac health. We have recently reported on the potential benefit of SGLT-2 inhibitors in terms of glucose control; recent data suggesting a specific cardiac benefit of this class of agent have obligated us to update our understanding of this class of drugs. This review focuses, in general, on the increasing awareness of the effects of diabetes medications on cardiac health and, more specifically, on newer agents, including incretin-based therapies and SGLT-2 inhibitors. PMID- 26677931 TI - SCMMTP: identifying and characterizing membrane transport proteins using propensity scores of dipeptides. AB - BACKGROUND: Identifying putative membrane transport proteins (MTPs) and understanding the transport mechanisms involved remain important challenges for the advancement of structural and functional genomics. However, the transporter characters are mainly acquired from MTP crystal structures which are hard to crystalize. Therefore, it is desirable to develop bioinformatics tools for the effective large-scale analysis of available sequences to identify novel transporters and characterize such transporters. RESULTS: This work proposes a novel method (SCMMTP) based on the scoring card method (SCM) using dipeptide composition to identify and characterize MTPs from an existing dataset containing 900 MTPs and 660 non-MTPs which are separated into a training dataset consisting 1,380 proteins and an independent dataset consisting 180 proteins. The SCMMTP produced estimating propensity scores for amino acids and dipeptides as MTPs. The SCMMTP training and test accuracy levels respectively reached 83.81% and 76.11%. The test accuracy of support vector machine (SVM) using a complicated classification method with a low possibility for biological interpretation and position-specific substitution matrix (PSSM) as a protein feature is 80.56%, thus SCMMTP is comparable to SVM-PSSM. To identify MTPs, SCMMTP is applied to three datasets including: 1) human transmembrane proteins, 2) a photosynthetic protein dataset, and 3) a human protein database. MTPs showing alpha-helix rich structure is agreed with previous studies. The MTPs used residues with low hydration energy. It is hypothesized that, after filtering substrates, the hydrated water molecules need to be released from the pore regions. CONCLUSIONS: SCMMTP yields estimating propensity scores for amino acids and dipeptides as MTPs, which can be used to identify novel MTPs and characterize transport mechanisms for use in further experiments. AVAILABILITY: http://iclab.life.nctu.edu.tw/iclab_webtools/SCMMTP/. PMID- 26677932 TI - PCTFPeval: a web tool for benchmarking newly developed algorithms for predicting cooperative transcription factor pairs in yeast. AB - BACKGROUND: Computational identification of cooperative transcription factor (TF) pairs helps understand the combinatorial regulation of gene expression in eukaryotic cells. Many advanced algorithms have been proposed to predict cooperative TF pairs in yeast. However, it is still difficult to conduct a comprehensive and objective performance comparison of different algorithms because of lacking sufficient performance indices and adequate overall performance scores. To solve this problem, in our previous study (published in BMC Systems Biology 2014), we adopted/proposed eight performance indices and designed two overall performance scores to compare the performance of 14 existing algorithms for predicting cooperative TF pairs in yeast. Most importantly, our performance comparison framework can be applied to comprehensively and objectively evaluate the performance of a newly developed algorithm. However, to use our framework, researchers have to put a lot of effort to construct it first. To save researchers time and effort, here we develop a web tool to implement our performance comparison framework, featuring fast data processing, a comprehensive performance comparison and an easy-to-use web interface. RESULTS: The developed tool is called PCTFPeval (Predicted Cooperative TF Pair evaluator), written in PHP and Python programming languages. The friendly web interface allows users to input a list of predicted cooperative TF pairs from their algorithm and select (i) the compared algorithms among the 15 existing algorithms, (ii) the performance indices among the eight existing indices, and (iii) the overall performance scores from two possible choices. The comprehensive performance comparison results are then generated in tens of seconds and shown as both bar charts and tables. The original comparison results of each compared algorithm and each selected performance index can be downloaded as text files for further analyses. CONCLUSIONS: Allowing users to select eight existing performance indices and 15 existing algorithms for comparison, our web tool benefits researchers who are eager to comprehensively and objectively evaluate the performance of their newly developed algorithm. Thus, our tool greatly expedites the progress in the research of computational identification of cooperative TF pairs. PMID- 26677933 TI - The effect of 1-week feed restriction on performance, digestibility of nutrients and digestive system development in the growing rabbit. AB - A 3 to 4 week feed restriction of about 20% to 25% of the free intake is widely applied in rabbit breeding systems to reduce post-weaning digestive disorders. However, a short intensive feed restriction is described in few studies and can be beneficial for growing rabbits due to a longer re-alimentation period. The aim of this study was to evaluate the effect of ad libitum (AL) and two restriction levels of feeding (50 and 65 g/rabbit per day) applied for 1 week on performance, gastrointestinal morphology and physiological parameters during the restriction and during the re-alimentation period. Rabbits were divided into three experimental groups: AL rabbits were fed AL, R1 rabbits were restricted from 42 to 49 days of age and received 50 g daily (29% of AL) and R2 rabbits were restricted at the same age and were fed 65 g of feed daily (37% of AL). In the 1(st) week after weaning and in the weeks after restriction, all the groups were fed AL. During the restriction period, daily weight gain (DWG) in R1 significantly dropped to 11% (experiment 1) and 5% (experiment 2) compared with rabbits in the AL group, although they were fed 29% of AL, whereas in the R2 group it decreased to 20% (experiment 1) and 10% (experiment 2). In the week following feed restriction, DWG in the restricted groups increased (P<0.001) to 166% and 148% in R1 and to 128% and 145% in R2. Restricted rabbits in both the experiments reached up to 90% to 93% of the final live weight (70 days) of the AL group. Over the entire experimental period, feed restriction significantly decreased feed intake to 85% to 88% of the AL group; however, the feed conversion ratio was lower (P<0.05) only in experiment 1 (-6% in R1 and -4% in R2). Digestibilities of CP and fat were not significantly higher during the restriction period and during the 1(st) week of re-alimentation compared with the AL group. Significant interactions between feeding regime and age revealed the shortest large intestine in the AL group at 49 days of age and the longest at 70 days in the AL and R1 groups. Small intestinal villi were significantly higher and the crypts were significantly deeper in the restricted groups. It could be concluded that short intensive feed restriction increased digestible area in the small and large intestines, including the height of villi and depth of crypts, which might be involved in the compensatory growth and defence mechanism. PMID- 26677934 TI - Effect of radiant heat at the birth site in farrowing crates on hypothermia and behaviour in neonatal piglets. AB - It has been documented that floor heating of the farrowing area in loose housed sows improves survival of piglets significantly. However, today, the majority of farrowing pens are designed with crating of sows and slatted floor at the birth site. The aim of this study was to investigate whether providing radiant heat at the birth site to new-born piglets in pens with crated sows reduced hypothermia, time to first milk intake and growth of the piglets during the 1(st) week. Second parity Danish Landrace*Yorkshire sows (n=36) were randomly divided into two groups: Control (CG) and heat (HG). In the area behind the sow (zone 1), two radiant heat panels were mounted above the slatted floor in the HG. The farrowings were attended, and the heaters were turned on at birth of first piglet and turned off 12 h after. Birth time, time to leave zone 1, time to first contact with udder and time to first suckling were registered by direct observation. The piglet's rectal temperature (RT) was measured 15, 30, 60, 120, 180, 240 min after birth and 12, 14 and 24 h after birth of first piglet. Piglets were weighed at birth, 24 and 48 h and 7 days after birth. Data were analysed in a mixed model in SAS. The drop in RT was lower in HG compared with CG (P=0.002), and the RT in HG remained higher than in CG from 30 to 240 min after birth (P<0.05), whereas no difference was found at 12 h after birth of first piglet (P=0.92). Piglets in HG stayed longer in zone 1 than those in CG (P=0.01), whereas time to reach udder (P=0.35) and to first suckling (P=0.56) did not differ. No difference in weight gain was found between piglets in HG and CG at 24 h (P=0.23), 48 h (P=0.28) and 7 days after birth (P=0.44). Birth weight had a positive effect on RT (P<0.001) and reduced time to leave zone 1 (P<0.01), reach udder (P<0.001) and time to first suckling (P<0.001). The results showed that radiant heating behind the sows reduced hypothermia in new-born piglets and indicate that providing heat during the first half hour after birth is important. PMID- 26677935 TI - Carcass and meat quality traits of chickens fed diets concurrently supplemented with vitamins C and E under constant heat stress. AB - The objective of this study was to determine if a diet supplemented simultaneously with vitamins C and E would alleviate the negative effects of heat stress, applied between 28 and 42 days of age, on performance, carcass and meat quality traits of broiler chickens. A total of 384 male broiler chickens were assigned to a completely randomized design, with a 2*3 factorial arrangement (diet with or without vitamin supplementation and two ambient temperatures plus a pair-feeding group) and 16 replicates. Chickens were kept in thermoneutral conditions up to 28 days of age. They were then housed in groups of four per cage, in three environmentally controlled chambers: two thermoneutral (22.5 and 22.6 degrees C) and one for heat stress (32 degrees C). Half the chickens were fed a diet supplemented with vitamins C (257 to 288 mg/kg) and E (93 to 109 mg/kg). In the thermoneutral chambers, half of the chickens were pair-fed to heat stressed chickens, receiving each day the average feed intake recorded in the heat stress chamber in the previous day. Meat physical quality analyses were performed on the pectoralis major muscle. No ambient temperature*diet supplementation interaction effects were detected on performance, carcass, or meat quality traits. The supplemented diet resulted in lower growth performance, attributed either to a carry-over effect of the lower initial BW, or to a possible catabolic effect of vitamins C and E when supplemented simultaneously at high levels. Heat stress reduced slaughter and carcass weights, average daily gain and feed intake, and increased feed conversion. Growth performance of pair fed chickens was similar to that of heat stressed chickens. Exposure to heat stress increased carcass and abdominal fat percentages, but reduced breast, liver and heart percentages. Pair-fed chickens showed the lowest fat percentage and their breast percentage was similar to controls. Heat stress increased meat pH and negatively affected meat color and cooking loss. In pair-fed chickens, meat color was similar to the heat stressed group. Shear force was not influenced by heat stress, but pair-fed chickens showed the tenderest meat. In conclusion, reduction in growth performance and negative changes in meat color in heat stressed chickens were attributed to depression in feed intake, whereas negative changes in body composition, higher meat pH and cooking loss were credited to high ambient temperature per se. Diet supplementation with vitamins C and E as antioxidants did not mitigate any of these negative effects. PMID- 26677936 TI - Asthma phenotypes and IgE responses. AB - The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma.In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcepsilonRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcepsilonRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma. PMID- 26677937 TI - Pharmacists' interventions on clinical asthma outcomes: a systematic review. AB - The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019). PMID- 26677938 TI - Social inequalities in wheezing in children: findings from the UK Millennium Cohort Study. AB - Wheezing in childhood is socially patterned, but it is unclear what factors explain the social differences.Regression analysis of the UK Millennium Cohort Study, based on 11 141 singleton children who participated at ages 9 months and 3, 5 and 7 years. Relative risk ratios (RRR) for early and persistent/relapsing wheeze were estimated using multinomial regression, according to measures of socioeconomic circumstances. Maternal, antenatal and early-life characteristics were assessed as potential mediators.Children of mothers with no educational qualifications were more likely to have both wheeze types, compared to children of mothers with degree-level qualifications (RRR 1.53, 95% CI 1.26-1.86 for early wheeze; 1.32 95% CI 1.04-1.67 for persistent/relapsing wheeze). Controlling for maternal age, smoking during pregnancy and breastfeeding removed the elevated risk of wheezing. Male sex, maternal age, body mass index, atopy, smoking during pregnancy, preterm birth, breastfeeding, exposure to other children and furry pets were independently associated with wheezing, but the pattern of association varied between wheezing types.In this representative UK cohort, adjustment for maternal smoking during pregnancy and breastfeeding removed the socioeconomic inequalities in common wheezing phenotypes. Policies to reduce the social gradient in these risk factors may reduce inequalities in wheezing and asthma. PMID- 26677939 TI - Incidence of airflow limitation in subjects 65-100 years of age. AB - The true incidence of chronic obstructive pulmonary disease is largely unknown, because the few longitudinal studies performed have used diagnostic criteria no longer recommended by either the European Respiratory Society or the American Thoracic Society (ATS).We studied the incidence and significance of airflow limitation in a population-based geriatric sample using both an age-dependent predicted lower limit of normal (LLN) value and a fixed-ratio spirometric criterion.Out of 2025 subjects with acceptable spirometry at baseline, 984 subjects aged 65-100 years completed a 6-year follow-up visit. Smoking habits were registered at baseline. Exclusion criteria were non-acceptable spirometry performance according to ATS criteria and inability to communicate. Airflow limitation was defined both according to forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7 and 50 years old.The present study, therefore, evaluated the pulmonary haemodynamic responses to maximum upright incremental cycling exercise in consecutive subjects who underwent an invasive cardiopulmonary exercise testing for unexplained exertional intolerance, deemed normal based on preserved exercise capacity and normal resting supine haemodynamics. Subjects aged >50 years old (n=41) were compared with subjects <=50 years old (n=25). ULNs were calculated as mean + 2 sdPeak exercise mean pulmonary arterial pressure was not different for subjects >50 and <=50 years old (23 +/- 5 versus 22 +/- 4 mmHg, p=0.22), with ULN of 33 and 30 mmHg, respectively. Peak cardiac output was lower in older subjects (median (interquartile range): 12.1 (9.4-14.2)versus16.2 (13.8-19.2) L.min(-1), p<0.001). Peak pulmonary vascular resistance was higher in older subjects compared with younger subjects (mean +/- sd: 1.20 +/- 0.45 versus 0.82 +/- 0.26 Wood units, p<0.001), with ULN of 2.10 and 1.34 Wood units, respectively.We observed that subjects >50 and <= 50 years old have different pulmonary vascular responses to exercise. Older subjects have higher pulmonary vascular resistance at peak exercise, resulting in different exercise haemodynamics ULNs compared with the younger population. PMID- 26677942 TI - Asthma and respiratory allergy prevalence is still increasing among Finnish young adults. PMID- 26677943 TI - Deletion of Tricellulin Causes Progressive Hearing Loss Associated with Degeneration of Cochlear Hair Cells. AB - Tricellulin (also known as MARVELD2) is considered as a central component of tricellular tight junctions and is distributed among various epithelial tissues. Although mutations in the gene encoding tricellulin are known to cause deafness in humans (DFNB49) and mice, the influence of its systemic deletion in vivo remains unknown. When we generated tricellulin-knockout mice (Tric(-/-)), we found an early-onset rapidly progressive hearing loss associated with the degeneration of hair cells (HCs); however, their body size and overall appearance were normal. Tric(-/-) mice did not show any morphological change pertaining to other organs such as the gastrointestinal tract, liver, kidney, thyroid gland and heart. The endocochlear potential (EP) was normal in Tric(-/-) mice, suggesting that the tight junction barrier is maintained in the stria vascularis, where EP is generated. The degeneration of HCs, which occurred after the maturation of EP, was prevented in the culture medium with an ion concentration similar to that of the perilymph. These data demonstrate the specific requirement of tricellulin for maintaining ion homeostasis around cochlear HCs to ensure their survival. The Tric(-/-) mouse provides a new model for understanding the distinct roles of tricellulin in different epithelial systems as well as in the pathogenesis of DFNB49. PMID- 26677944 TI - TRPV4 associates environmental temperature and sex determination in the American alligator. AB - Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual's genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 degrees C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 degrees C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism. PMID- 26677945 TI - Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala. AB - Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders. PMID- 26677946 TI - Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents. AB - Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6 18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children. PMID- 26677947 TI - HIV-1 Transgenic Rat Prefrontal Cortex Hyper-Excitability is Enhanced by Cocaine Self-Administration. AB - The medial prefrontal cortex (mPFC) is dysregulated in HIV-1-infected humans and the dysregulation is enhanced by cocaine abuse. Understanding mPFC pathophysiology in this comorbid state has been hampered by the dearth of relevant animal models. To help fill this knowledge gap, electrophysiological assessments were made of mPFC pyramidal neurons (PN) from adult male HIV-1 transgenic (Tg) F344 rats (which express seven of the nine HIV-1 toxic proteins) and non-Tg F344 rats that self-administered cocaine for 14 days (COC-SA), as well as saline-yoked controls (SAL-Yoked) and experimentally naive Tg and non-Tg rats. Forebrain slices were harvested and prepared for whole-cell patch-clamp recording, and in treated rats, this occurred after 14-18 days of forced abstinence. Aged-matched rats were used for immunohistochemical detection of the L-channel protein, Cav1.2-alpha1c. We determined that: (i) the two genotypes acquired the operant task and maintained similar levels of COC-SA, (ii) forced abstinence from COC-SA enhanced mPFC PN excitability in both genotypes, and neurons from Tg rats exhibited the greatest pathophysiology, (iii) neurons from SAL-Yoked Tg rats were more excitable than those from SAL-Yoked non-Tg rats, and in Tg rats (iv) blockade of L-type Ca(2+) channels reduced the enhanced excitability, and (v) Cav1.2-immunoreactivity was increased. These findings provide the first assessment of the mPFC pathophysiology in a rodent model of HIV 1-mediated neuropathology with and without cocaine self-administration. Outcomes reveal an enhanced cortical excitability during chronic exposure to HIV-1 proteins that is excessively exacerbated with cocaine abuse. Such neuropathophysiology may underlie the cognitive dysregulation reported for comorbid humans. PMID- 26677948 TI - Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. AB - Kindlins are FERM-containing cytoplasmic proteins that regulate integrin-mediated cell-cell and cell-extracellular matrix (ECM) attachments. Kindlin-3 is expressed in hematopoietic cells, platelets, and endothelial cells. Studies have shown that kindlin-3 stabilizes cell adhesion mediated by beta1, beta2, and beta3 integrins. Apart from integrin cytoplasmic tails, kindlins are known to interact with other cytoplasmic proteins. Here we demonstrate that kindlin-3 can associate with ribosome via the receptor for activated-C kinase 1 (RACK1) scaffold protein based on immunoprecipitation, ribosome binding, and proximity ligation assays. We show that kindlin-3 regulates c-Myc protein expression in the human chronic myeloid leukemia cell line K562. Cell proliferation was reduced following siRNA reduction of kindlin-3 expression and a significant reduction in tumor mass was observed in xenograft experiments. Mechanistically, kindlin-3 is involved in integrin alpha5beta1-Akt-mTOR-p70S6K signaling; however, its regulation of c-Myc protein expression could be independent of this signaling axis. PMID- 26677950 TI - Sixteen years of experience with persistent chylothorax in children. AB - BACKGROUND: Persistent chylothorax in children is rare. Conservative management represents the gold standard but, in case of failure (persistent effusion or relapse), surgery must be considered. This paper aimed at presenting our series of patients who underwent surgical treatment of persistent idiopathic chylothorax and at discussing the role of thoracic duct ligation in its management. METHODS: We included all patients who underwent surgery for persistent chylothorax in the period between January 1994 and January 2010. RESULTS: Nine patients were included (median age 25 months). Five patients had primitive or idiopathic chylothorax. Five patients had right-sided chylothorax, 3 left-sided, and 1 bilateral. Pleurodesis was applied to 8 patients (bilateral in one) and thoracic duct ligation to 4 patients for a total of 12 procedures in 9 patients. Complete cessation occurred within a median of 5 days (range 2 to 10) after thoracic duct ligation and 10 days (range 4 to 25) after pleurodesis. In 3 patients (all with right sided effusion and a median daily output higher than 20 ml/kg) pleurodesis failed and thoracic duct ligation was subsequently required to definitively treat chylothorax. Conversely, 5 patients were effectively treated with pleurodesis and 1 with thoracic duct ligation alone. Regardless of previous procedures, none of the patients who underwent thoracic duct ligation experienced relapses. CONCLUSIONS: Although based on a small number of patients, our experience confirmed that thoracic duct ligation represents an effective therapeutic option for persistent unresponsive chylothorax. In cases of right sided effusion with high output rate (>20 mL/kg) thoracic duct ligation might be considered as first choice treatment. PMID- 26677949 TI - Liquid immersion thermal crosslinking of 3D polymer nanopatterns for direct carbonisation with high structural integrity. AB - The direct pyrolytic carbonisation of polymer patterns has attracted interest for its use in obtaining carbon materials. In the case of carbonisation of nanopatterned polymers, the polymer flow and subsequent pattern change may occur in order to relieve their high surface energies. Here, we demonstrated that liquid immersion thermal crosslinking of polymer nanopatterns effectively enhanced the thermal resistance and maintained the structure integrity during the heat treatment. We employed the liquid immersion thermal crosslinking for 3D porous SU8 photoresist nanopatterns and successfully converted them to carbon nanopatterns while maintaining their porous features. The thermal crosslinking reaction and carbonisation of SU8 nanopatterns were characterised. The micro crystallinity of the SU8-derived carbon nanopatterns was also characterised. The liquid immersion heat treatment can be extended to the carbonisation of various polymer or photoresist nanopatterns and also provide a facile way to control the surface energy of polymer nanopatterns for various purposes, for example, to block copolymer or surfactant self-assemblies. PMID- 26677951 TI - Association of adolescents' weight status with life satisfaction: role of self, peers, family and school perception; the CASPIAN-IV study. AB - : Although many public health programs have focused on prevention and control of obesity, their efficacy mostly depends on personal factors including perception of weight and personal understanding of the concept of being overweight. This study aims to investigate the association of adolescent's weight status with life satisfaction and explore the role of self, peers, family and school perception in this association. METHODS: Data were obtained from the fourth school-based survey entitled "Childhood and Adolescence Surveillance and Prevention of Adult Non communicable Disease" (CASPIAN) study. This survey was conducted among 14880 urban and rural students aged 6-18 years. Two sets of valid and reliable questionnaire, obtained from Global School Health Survey (GSHS) were completed by students and their parents. The students' questionnaire had several questions including life satisfaction and the perception of weight, peers, family and school. RESULTS: The study had a participation rate of 90.6% including 50.8% boys and 76% urban residents. Significant differences existed in body mass index (BMI) and in perception of weight among girls and boys. Moreover, the prevalence of depression and being bullied were higher among girls and boys, respectively.Significant association was documented between life satisfaction and all variables including perception of weight, peers, family and school; the only exception was for BMI (p<0.05). In addition, students with normal weight had significantly higher life satisfaction in comparison with their obese counterparts (p<0.05). CONCLUSION: The present study documented significant association between life satisfaction and perception of self, peer, family and school with the exception of BMI in both gender. PMID- 26677952 TI - EBV induces HERV-K and HERV-W expression in pediatrics liver transplant recipients? AB - OBJECTIVES: Human endogenous retrovirus (HERVs) constitute approximately 8% of the human genome. Induction of HERV transcription is possible under certain circumstances, and may have a possible role in some pathological conditions. Aim of the present study was to verify whether HERV-W and K activation by EBV might occur also in vivo, during EBV infection, in pediatric liver transplant recipients. METHODS: A total of 35 pediatric liver transplant (LT) patients who received LT at the University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital were included. The samples was grouped in EBV negative and positive. RESULT: We found that HERV-K, and HERV-W expression levels showed no differences between the two groups (p=0.533 HERV-W and p=0.6017 HERV-K). There was not was a significant difference p=0.1894 and 0.1705 for HERV W and -K respectively when we compared transplant recipients group with high EBV viral load vs others transplant recipients. CONCLUSION: Our data suggest that EBV does not facilitate in vivo HERV activation. PMID- 26677953 TI - A Revisit to High Thermoelectric Performance of Single-layer MoS2. AB - Both electron and phonon transport properties of single layer MoS2 (SLMoS2) are studied. Based on first-principles calculations, the electrical conductivity of SLMoS2 is calculated by Boltzmann equations. The thermal conductivity of SLMoS2 is calculated to be as high as 116.8 Wm(-1) K(-1) by equilibrium molecular dynamics simulations. The predicted value of ZT is as high as 0.11 at 500 K. As the thermal conductivity could be reduced largely by phonon engineering, there should be a high possibility to enhance ZT in the SLMoS2-based materials. PMID- 26677954 TI - The infertility trap: how defeat and entrapment affect depressive symptoms. AB - STUDY QUESTION: Does the perception of failure without a solution or way forward of infertile couples have a mediator role between the importance couples attribute to parenthood and depressive symptoms? SUMMARY ANSWER: The perception of failure without a solution or way forward, assessed by feelings of entrapment and defeat, mediates the effect of the importance of parenthood on depressive symptoms of infertile men and women. WHAT IS KNOWN ALREADY: Research has documented that the heightened importance of parenthood affects infertile couples' adjustment to infertility and medical treatments. However, it remains unclear which psychological mechanisms and perceptions may underlie the association between having parenthood as a nuclear aspect of life and presenting depressive symptoms related to difficulties in accomplishing that important life goal. Although these links have been scantly addressed in infertility, previous studies have pointed to the role that perceptions of defeat and entrapment have in several psychopathological conditions. STUDY DESIGN, SIZE, DURATION: The study was cross-sectional. Couples pursuing medical treatment for their fertility problems were invited to participate by their doctors in several public and private clinics. Data collection took place between July 2009 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred forty-seven infertile couples consented to participate in the study. Both couple members (147 women and 147 men) completed a set of self-report instruments for the assessment of depressive symptoms, perceptions of defeat and entrapment, importance of parenthood and rejection of a childfree lifestyle. Analyses were conducted through Structural Equation Modeling and followed a dyadic analysis strategy, allowing for controlling the interdependence of the data. MAIN RESULTS AND THE ROLE OF CHANCE: The hypothesized tested model showed a very good fit to the data [(chi(2) = 68.45, P = 0.014, comparative fit index = 0.98, standardized root-mean square residual = 0.06 and root mean square error of approximation = 0.06] and explained 67 and 58% of the variability in depressive symptoms in women and men, respectively. Results revealed that the importance of parenthood does not have a direct effect on depressive symptoms of infertile men and women, but an indirect effect, by affecting the perception of having failed and not being able to solve it or move forward [women: estimate for indirect effect: 0.38 (bias corrected (BC) 95% confidence interval (CI) = 0.25; 0.56; P < 0.001); men: estimate for indirect effect: 0.23 (BC 95% CI = 0.06; 0.40; P = 0.013)]. LIMITATIONS, REASONS FOR CAUTION: The study was cross-sectional, which does not allow for the establishment of causality. Another limitation is the heterogeneity of the sample, as participants were recruited at various stages of their fertility care. In addition, due to the specific nature of the variables, further studies are needed to establish exactly how the relationship between defeat and entrapment and depression operates, as the mechanism may be bidirectional. WIDER IMPLICATIONS OF THE FINDINGS: This study emphasizes the role of perceptions of defeat and entrapment on the psychological adjustment to infertility and assisted reproduction. These emotional processes should be taken into consideration and targeted in psychological interventions of couples undergoing medical treatments for infertility. In fact, although parenthood may be perceived as a core purpose for many couples dealing with difficulties in conceiving, it is only when these difficulties are experienced as failures without a resolution and as inescapable, that couples are prone to develop depressive symptoms. STUDY FUNDING/COMPETING INTERESTS: This research has been supported by the first author Ph.D. Grant (SFRH/BD/68392/2010), sponsored by the Portuguese Foundation for Science and Technology (FCT). The authors have no conflict of interests. TRIAL REGISTRATION NUMBER: N/A. PMID- 26677955 TI - Maternal stress before and during pregnancy and subsequent infertility in daughters: a nationwide population-based cohort study. AB - STUDY QUESTION: Is maternal stress following the death of a close relative before or during pregnancy associated with the risk of infertility in daughters? SUMMARY ANSWER: Compared with unexposed women, women whose mothers had experienced bereavement stress during, or in the year before, pregnancy had a similar risk of infertility overall, but those exposed to maternal bereavement during the first trimester had a higher risk of infertility. WHAT IS KNOWN ALREADY: Animal studies have shown that prenatal maternal stress results in reduced offspring fertility. In humans, there is evidence that girls who have been prenatally exposed to stress have a more masculine behaviour and a slight delay in having their first child. STUDY DESIGN, SIZE AND DURATION: This population-based cohort study, included 660 099 females born in Denmark between 1 January 1973 and 31 December 1993 to mothers of Danish origin and with at least one living relative in the exposure window, and followed the women through 31 December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 13 334 women (2.0%) were considered prenatally exposed to stress because their mother had lost a spouse/partner, a child, a parent, or a sibling during pregnancy or in the year before conception. Infertility was defined as any record of infertility treatment or diagnosis of female infertility. We considered the date of onset as the date of the first appearance of any such record. The association between exposure and outcome was examined using hazard ratios (HR) with 95% confidence intervals (CI). MAIN RESULTS AND THE ROLE OF CHANCE: Based on our definition, 40 052 (6.5%) women were infertile in the follow-up period (median age at the end of follow-up: 26.7 years, maximum age: 39 years). Overall, prenatal exposure to maternal stress was not associated with risk of infertility (adjusted HR = 1.04 [CI: 0.95-1.14]). However, women prenatally exposed during the first trimester had a higher estimated risk (adjusted HR = 1.40 [CI: 1.05-1.86]). These findings were consistent in subgroups defined by the relationship of the mother to the deceased and in several sensitivity analyses, including a sibling-matched analysis, and in analyses restricted to women who were married or cohabitating with a man, or to women born at term. LIMITATIONS, REASONS FOR CAUTION: We did not have a direct measure of stress, but bereavement due to death of a close relative is likely to be very stressful. We based the timing of exposure on the date of the death of the family member, although the stress may well have started earlier. Infertility was also defined indirectly, and many women in the cohort were too young at the end of the follow-up to have been diagnosed. However, misclassification of the outcome was most likely non-differential, and the similar results from all sensitivity analyses suggest that it is unlikely that the effect observed in first trimester exposure would be due to chance. WIDER IMPLICATIONS OF THE FINDINGS: Prenatal exposure to maternal stress in the first trimester may affect the later fecundity of daughters. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from the European Research Council (ERC-2010-StG-260242 PROGEURO) to the ProgEuro project (http://progeuro.au.dk). O.P.-R. is partly supported by a fellowship from Aarhus University and a travel grant from Oticon Fonden. The authors report no conflict of interests. PMID- 26677956 TI - Knowledge, attitudes, and intentions toward fertility awareness and oocyte cryopreservation among obstetrics and gynecology resident physicians. AB - STUDY QUESTION: What knowledge, attitudes and intentions do US obstetrics and gynecology (OB/GYN) residents have toward discussing age-related fertility decline and oocyte cryopreservation with their patients? SUMMARY ANSWER: Most OB/GYN residents believe that age-related fertility decline, but not oocyte cryopreservation, should be discussed during well-woman annual exams; furthermore, nearly half of residents overestimated the age at which female fertility markedly declines. WHAT IS KNOWN ALREADY: Oocyte cryopreservation can be utilized to preserve fertility potential. Currently, no studies of US OB/GYN residents exist that question their knowledge, attitudes, and intentions toward discussing age-related fertility decline and oocyte cryopreservation with patients. STUDY DESIGN, SIZE, DURATION: A cross-sectional online survey was conducted during the fall of 2014 among residents in American Council for Graduate (ACOG) Medical Education-approved OB/GYN residency programs. Program directors were emailed via the ACOG Council on Resident Education in Obstetrics and Gynecology server listing and asked to solicit resident participation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants included 238 residents evenly distributed between post-graduate years 1-4 with varied post-residency plans; 90% of residents were women and 75% were 26-30 years old. The survey was divided into three sections: demographics, fertility awareness, and attitudes toward discussing fertility preservation options with patients. Descriptive and inferential statistics were conducted. MAIN RESULTS AND THE ROLE OF CHANCE: A strong majority of residents (83%) believed an OB/GYN should initiate discussions about age-related fertility decline with patients (mean patient age 31.8), and 73% percent believed these discussions should be part of an annual exam. One third of residents overestimated the age at which there is a slight decline in female fertility, while nearly half of residents overestimated the age at which female fertility markedly declines. Over three-quarters of residents (78.4%) also overestimated the likelihood of success using assisted reproductive treatments (ARTs). Residents were likely to support oocyte cryopreservation in cancer patients irrespective of the woman's age, but much less likely to support elective oocyte cryopreservation. For elective oocyte cryopreservation, 40% believed OB/GYNs should initiate discussions with patients (mean age 31.1), while only 20% believed this topic should be part of an annual exam. LIMITATIONS, REASONS FOR CAUTION: Because the study invitation was sent through US OB/GYN residency program directors rather than directly to residents, it is possible that some residents did not receive the invitation to participate. This limits the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Within the USA, there appears to be a critical need for improved education on fertility decline in OB/GYN residency programs. To promote informed reproductive decision making among patients, efforts should be made to help OB/GYNs provide comprehensive fertility education to all women, while also respecting patient choices. STUDY FUNDING/COMPETING INTERESTS: None. PMID- 26677957 TI - Embryo donation and counselling for the welfare of donors, recipients, their families and children. AB - STUDY QUESTION: How do counsellors facilitating known 'open' embryo donation (ED) experience their roles and responsibilities? SUMMARY ANSWER: Counsellors regard counselling for ED as entailing significant responsibility to ensure that the longer-term implications of the practice are understood and that positive relationships are established that will promote the well-being of donors, recipients, their families and the children involved. WHAT IS KNOWN ALREADY: While counselling is frequently recommended in third-party assisted reproduction, there has been little research into the experiences of counsellors and their perceptions of their roles and responsibilities. STUDY DESIGN, SIZE, DURATION: Fertility counsellors were interviewed between March and October 2012 as to their experiences and perceptions of their roles and responsibilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fertility counsellors were recruited from across New Zealand and interviews were conducted with all nine counsellors involved in ED counselling. Interview data were analysed thematically to identify main themes. MAIN RESULTS AND THE ROLE OF CHANCE: Counsellors regard ED as a complex practice with enduring implications arising from the genetic link between donors and offspring, which is seen to bestow immutable social ties. They see their role as the provision of implications counselling and the facilitation of ongoing positive relationships between donors and recipients in an 'open' context. Counsellors express concern about their responsibility for promoting the welfare of all parties--including that of the child--the limitations of counselling, and the conflation of assessment and counselling roles. LIMITATIONS, REASONS FOR CAUTION: Experiences of counselling for ED may change over time as longer-term outcomes become more apparent. WIDER IMPLICATIONS OF THE FINDINGS: Further consideration needs to be given as to how the welfare principle may best be operationalised in counselling practice, particularly in contexts of 'open' donation. STUDY FUNDING/COMPETING INTERESTS: This study was funded by an AUT University Faculty of Health and Environmental Sciences research grant. The authors have no conflicts of interest to declare. PMID- 26677958 TI - Factors affecting the gene expression of in vitro cultured human preimplantation embryos. AB - STUDY QUESTION: What is the relative effect of common environmental and biological factors on transcriptome changes during human preimplantation development? SUMMARY ANSWER: Developmental stage and maternal age had a larger effect on the global gene expression profile of human preimplantation embryos than the culture medium or oxygen concentration used in in vitro culture. WHAT IS KNOWN ALREADY: Studies on mouse and bovine embryos have shown that different conditions in the in vitro culture of embryos can lead to changes in transcriptome profiles. For humans, an effect of developmental stage on the transcriptome profile of embryos has been demonstrated, but studies on the effect of maternal age or culture conditions are lacking. STUDY DESIGN, SIZE, DURATION: Donated, good quality, day 4 cryopreserved human preimplantation embryos (N = 89) were randomized to be cultured in one of two culture media (G5 medium or HTF medium) and one of two oxygen concentrations (5% or 20%), with stratification for maternal age. Next to these variables, developmental stage after culture was taken into account in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos that developed to morula or blastocyst stage during these 2 days whose amplified mRNA passed our quality control criteria for microarray hybridization were individually examined for genome-wide gene expression (N = 37). MAIN RESULTS AND THE ROLE OF CHANCE: Based on the number of differentially expressed genes (DEGs), developmental stage (3519 DEGs) and maternal age (1258 DEGs) had a larger effect on the global gene expression profile of human preimplantation embryos than either tested culture medium (596 DEGs) or oxygen concentration (492 DEGs) used during in vitro culture. Interactions between the factors were found, indicating that culture conditions might have a different effect depending on the developmental stage or the maternal age of the embryos. Affected pathways included metabolism, cell cycle processes and oxidative phosphorylation. LIMITATIONS, REASONS FOR CAUTION: Culture of embryos for only 2 days might have limited the effect on global gene expression by the investigated culture conditions. Earlier stages of development (Day 0 until Day 4) were not analyzed and these embryos might respond differently to the experimental conditions. The freezing and thawing procedures might have had an effect on gene expression. RT PCR validation was not performed due to scarcity of the material. WIDER IMPLICATIONS OF THE FINDINGS: Our results show that when studying gene expression in single human preimplantation embryos under various experimental conditions, one should take into account the confounding effect of biological variables, such as developmental stage and maternal age. This makes these experiments different from gene expression experiments where these variables can be tightly controlled, for example when using cell lines. STUDY FUNDING/COMPETING INTERESTS: This study received no external funding and there were no competing interests. PMID- 26677959 TI - Characteristics of testis-specific phosphoglycerate kinase 2 and its association with human sperm quality. AB - STUDY QUESTION: Is there an association between the expression of phosphoglycerate kinase (PGK) 2 in spermatozoa and sperm quality in both elderly men and young asthenozoospermia patients? SUMMARY ANSWER: Spermatozoa from elderly men and young asthenozoospermia patients show decreased expression of PGK2, which has a close positive relationship with sperm quality. WHAT IS KNOWN ALREADY: PGK1 and PGK2 are involved in spermatogenesis and thought to be related to sperm motility. However, limited information is known about their temporal spatial expression in human spermatogenesis and their relationship with sperm quality. STUDY DESIGN, SIZE, DURATION: This was a case-control study including 30 healthy young males (aged 28-31 years), 30 elderly men (aged 68-70 years), and 30 asthenozoospermic patients (aged 25-40 years, progressive motility <32%) who donated semen samples. Furthermore, young testes samples were obtained from five fathers (27-33 years old) who had died in car accidents, while aged testes samples were obtained from five elderly fathers (78-82 years old) who were prostate cancer patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen samples from young adults, elderly men and asthenozoospermic patients were prepared, and their parameters were assessed by Computer-Aided Sperm Analysis (CASA). Sperm proteins were extracted for western blot analysis. Immunohistochemistry was used to characterize the cellular localization of PGK1 and PGK2 in testes samples. Sperm immunofluorescence quantification experiments identified the differential expression of PGK1 and PGK2 in sperm from young adults, elderly men and asthenozoospermic patients. Antibodies against PGK1 and PGK2 were used to test their influence on sperm motility and penetration into viscous media. A modified Kremer test using methyl cellulose was adopted to assess sperm function via penetration into viscous media. MAIN RESULTS AND THE ROLE OF CHANCE: Cellular localization analysis showed that PGK1 was mainly expressed in spermatogonia whereas PGK2 was mainly expressed in round spermatids. Expression levels of both PGKs were significantly decreased in the testis with ageing (P < 0.05). Western blot and immunofluorescence quantification showed markedly lower expression of PGK2 (P < 0.05) in sperm from elderly men or asthenozoospermic patients compared sperm from with healthy young men. Sperm functional analysis validated the close relationship between expression of PGK2 and sperm motility (staining percentage, r = 0.60, P < 0.05; intensity, r = 0.59, P < 0.05). Use of an anti-PGK2 antibody on sperm significantly decreased their ability to penetrate into a cervical mucus substitute (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Before any clinical applications using PGK2 to assess sperm quality can be developed, more cases should be used to evaluate this approach. WIDER IMPLICATIONS OF THE FINDINGS: The study provides new insights into the role of PGKs in male reproduction. The results also indicate that PGK2 is a promising molecular candidate for the assessment of sperm quality and the screening of male contraceptive targets. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the National Natural Science Foundation of China (no. 81300533, 81370013 and 81000277) and Shandong Provincial Natural Science Foundation, China (ZR2013HQ002). The authors declare no competing financial interests. PMID- 26677960 TI - Reproductive outcomes in oocyte donation cycles are associated with donor BMI. AB - STUDY QUESTION: When adjusting for recipient BMI, is donor body mass index (BMI) associated with IVF outcomes in donor oocyte IVF cycles? SUMMARY ANSWER: Increasing oocyte donor BMI is associated with a reduction in clinical pregnancy and live birth rates. WHAT IS KNOWN ALREADY: Increased BMI has been associated with suboptimal reproductive outcomes, particularly in assisted reproductive technology (ART) cycles. However, it remains unclear if this association implies an effect of BMI on oocyte quality and/or endometrial receptivity. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of two hundred and thirty five consecutive fresh donor oocyte IVF cycles from 1 January 2007 through 31 December 2013 at the Massachusetts General Hospital (MGH) Fertility Center. PARTICIPANTS/MATERIALS, SETTING, METHODS: Analyses included a total of 202 oocyte donors and 235 total cycles. Following adjustments for recipient BMI, the relationship between donor BMI (categorized into quartiles) and IVF outcomes was assessed. MAIN RESULTS AND THE ROLE OF CHANCE: In the entire (anonymous and known) donor population, a reduced odds of clinical pregnancy (P-trend = 0.046) and live birth (P-trend = 0.06) was observed with increasing BMI quartile. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.9 (0.4-2.0), 0.5 (0.2-1.1) and 0.5 (0.2-1.1), and OR of live birth was 1.1 (0.5-2.6), 0.6 (0.3-1.2) and 0.6 (0.3-1.2) for quartiles 2 through 4 respectively. In anonymous donors only, the odds of clinical pregnancy (P-trend = 0.02) and live birth (P-trend = 0.03) also declined as BMI quartile increased. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.7 (0.3-1.7), 0.5 (0.2-1.1) and 0.4 (0.1-0.9), and OR of live birth was 0.9 (0.4-2.2), 0.5 (0.3-1.2) and 0.4 (0.2-1.1) for quartiles 2 through 4 respectively. LIMITATIONS, REASONS FOR CAUTION: Limitations include the retrospective design, sample size and data from a single institution. Clinical application may not be limited to oocyte donors, though caution should be used prior to applying these principles to the general population. Data should not be interpreted to mean that all oocyte donors should be restricted to a BMI of less than 21.2 kg/m(2). WIDER IMPLICATIONS OF THE FINDINGS: Following adjustments for the respective BMI of the oocyte donor and recipient, this study demonstrates an association of preconception BMI with subsequent IVF outcomes. The observations of this study are consistent with prior animal studies, suggest a possible effect of BMI at the oocyte level prior to fertilization and implantation, and warrant further investigation. STUDY FUNDING/COMPETING INTERESTS: None. PMID- 26677961 TI - Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period. AB - STUDY QUESTION: Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? SUMMARY ANSWER: Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post ovulatory infertility occurred for only 7-17% of the cycles. WHAT IS KNOWN ALREADY: The PdG threshold of 7.0 umol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. STUDY DESIGN, SIZE, DURATION: Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. MAIN RESULTS AND THE ROLE OF CHANCE: The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 umol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. LIMITATIONS, REASONS FOR CAUTION: The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. WIDER IMPLICATIONS OF THE FINDINGS: The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. STUDY FUNDING/COMPETING INTERESTS: This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare. PMID- 26677963 TI - OMPPM: online multiple palindrome pattern matching. AB - MOTIVATION: A palindrome is a string that reads the same forward and backward. Finding palindromic substructures is important in DNA, RNA or protein sequence analysis. We say that two strings of the same length are pal-equivalent if, for each possible centre, they have the same length of the maximal palindrome. Given a text T of length n and a pattern P of length m, we study the palindrome pattern matching problem that finds all indices i such that P and [Formula: see text] are pal-equivalent. RESULTS: We first solve the online palindrome pattern matching problem in O(m(2)) preprocessing time and O(mn) query time using O(m(2)) space. We then extend the problem for multiple patterns and solve the online multiple palindrome pattern matching problem in [Formula: see text] preprocessing time and [Formula: see text] query time using [Formula: see text] space, where M is the sum of all pattern lengths, mk is the longest pattern length and c is the number of pattern occurrences. AVAILABILITY AND IMPLEMENTATION: The source code for all algorithms is freely available at http://toc.yonsei.ac.kr/OMPPM CONTACT: kimhwee@cs.yonsei.ac.kr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26677962 TI - CG2AA: backmapping protein coarse-grained structures. AB - Coarse grain (CG) models allow long-scale simulations with a much lower computational cost than that of all-atom simulations. However, the absence of atomistic detail impedes the analysis of specific atomic interactions that are determinant in most interesting biomolecular processes. In order to study these phenomena, it is necessary to reconstruct the atomistic structure from the CG representation. This structure can be analyzed by itself or be used as an onset for atomistic molecular dynamics simulations. In this work, we present a computer program that accurately reconstructs the atomistic structure from a CG model for proteins, using a simple geometrical algorithm. AVAILABILITY AND IMPLEMENTATION: The software is free and available online at http://www.ic.fcen.uba.ar/cg2aa/cg2aa.py SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: lula@qi.fcen.uba.ar. PMID- 26677964 TI - Computational identification of piRNA targets on mouse mRNAs. AB - MOTIVATION: PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that are highly abundant in the germline. One important role of piRNAs is to defend genome integrity by guiding PIWI proteins to silence transposable elements (TEs), which have a high potential to cause deleterious effects on their host. The mechanism of piRNA-mediated post-transcriptional silencing was also observed to affect mRNAs, suggesting that piRNAs might play a broad role in gene expression regulation. However, there has been no systematic report with regard to how many protein-coding genes might be targeted and regulated by piRNAs. RESULTS: We trained a support vector machine classifier based on a combination of Miwi CLIP-Seq-derived features and position-derived features to predict the potential targets of piRNAs on mRNAs in the mouse. Reanalysis of a published microarray dataset suggested that the expression level of the 2587 protein-coding genes predicted as piRNA targets showed significant upregulation as a whole after abolishing the slicer activity of Miwi, supporting the conclusion that they are subject to piRNA-mediated regulation. AVAILABILITY AND IMPLEMENTATION: A web version of the method called pirnaPre as well as our results for browse is available at http://www.regulatoryrna.org/software/piRNA/piRNA_target_mRNA/index.php CONTACT: crs@sun5.ibp.ac.cn or heshunmin@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26677965 TI - DeNovo: virus-host sequence-based protein-protein interaction prediction. AB - MOTIVATION: Can we predict protein-protein interactions (PPIs) of a novel virus with its host? Three major problems arise: the lack of known PPIs for that virus to learn from, the cost of learning about its proteins and the sequence dissimilarity among viral families that makes most methods inapplicable or inefficient. We develop DeNovo, a sequence-based negative sampling and machine learning framework that learns from PPIs of different viruses to predict for a novel one, exploiting the shared host proteins. We tested DeNovo on PPIs from different domains to assess generalization. RESULTS: By solving the challenge of generating less noisy negative interactions, DeNovo achieved accuracy up to 81 and 86% when predicting PPIs of viral proteins that have no and distant sequence similarity to the ones used for training, receptively. This result is comparable to the best achieved in single virus-host and intra-species PPI prediction cases. Thus, we can now predict PPIs for virtually any virus infecting human. DeNovo generalizes well; it achieved near optimal accuracy when tested on bacteria-human interactions. AVAILABILITY AND IMPLEMENTATION: Code, data and additional supplementary materials needed to reproduce this study are available at: https://bioinformatics.cs.vt.edu/~alzahraa/denovo CONTACT: alzahraa@vt.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26677966 TI - Establishing a Link Between Prescription Drug Abuse and Illicit Online Pharmacies: Analysis of Twitter Data. AB - BACKGROUND: Youth and adolescent non-medical use of prescription medications (NUPM) has become a national epidemic. However, little is known about the association between promotion of NUPM behavior and access via the popular social media microblogging site, Twitter, which is currently used by a third of all teens. OBJECTIVE: In order to better assess NUPM behavior online, this study conducts surveillance and analysis of Twitter data to characterize the frequency of NUPM-related tweets and also identifies illegal access to drugs of abuse via online pharmacies. METHODS: Tweets were collected over a 2-week period from April 1-14, 2015, by applying NUPM keyword filters for both generic/chemical and street names associated with drugs of abuse using the Twitter public streaming application programming interface. Tweets were then analyzed for relevance to NUPM and whether they promoted illegal online access to prescription drugs using a protocol of content coding and supervised machine learning. RESULTS: A total of 2,417,662 tweets were collected and analyzed for this study. Tweets filtered for generic drugs names comprised 232,108 tweets, including 22,174 unique associated uniform resource locators (URLs), and 2,185,554 tweets (376,304 unique URLs) filtered for street names. Applying an iterative process of manual content coding and supervised machine learning, 81.72% of the generic and 12.28% of the street NUPM datasets were predicted as having content relevant to NUPM respectively. By examining hyperlinks associated with NUPM relevant content for the generic Twitter dataset, we discovered that 75.72% of the tweets with URLs included a hyperlink to an online marketing affiliate that directly linked to an illicit online pharmacy advertising the sale of Valium without a prescription. CONCLUSIONS: This study examined the association between Twitter content, NUPM behavior promotion, and online access to drugs using a broad set of prescription drug keywords. Initial results are concerning, as our study found over 45,000 tweets that directly promoted NUPM by providing a URL that actively marketed the illegal online sale of prescription drugs of abuse. Additional research is needed to further establish the link between Twitter content and NUPM, as well as to help inform future technology-based tools, online health promotion activities, and public policy to combat NUPM online. PMID- 26677967 TI - Enhanced photovoltaic performance of ultrathin Si solar cells via semiconductor nanocrystal sensitization: energy transfer vs. optical coupling effects. AB - Excitonic energy transfer (ET) offers exciting opportunities for advances in optoelectronic devices such as solar cells. While recent experimental attempts have demonstrated its potential in both organic and inorganic photovoltaics (PVs), what remains to be addressed is quantitative understanding of how different ET modes contribute to PV performance and how ET contribution is differentiated from the classical optical coupling (OC) effects. In this study, we implement an ET scheme using a PV device platform, comprising CdSe/ZnS nanocrystal energy donor and 500 nm-thick ultrathin Si acceptor layers, and present the quantitative mechanistic description of how different ET modes, distinguished from the OC effects, increase the light absorption and PV efficiency. We find that nanocrystal sensitization enhances the short circuit current of ultrathin Si solar cells by up to 35%, of which the efficient ET, primarily driven by a long-range radiative mode, contributes to 38% of the total current enhancement. These results not only confirm the positive impact of ET but also provide a guideline for rationally combining the ET and OC effects for improved light harvesting in PV and other optoelectronic devices. PMID- 26677968 TI - Simple entry into N-tert-butyl-iminophosphonamide rare-earth metal alkyl and chlorido complexes. AB - In situ protolysis reaction of a highly basic and sterically hindered N,N'-di tert-butyl-iminophosphonamide ligand Ph2P([double bond, length as m-dash]N tBu)(NH-tBu) = (NPN(tBu))H (1) with equimolar or hemimolar amounts of rare-earth metal tris-alkyls leads to dialkyl [(NPN(tBu))Ln(CH2SiMe3)2(THF)n] (Ln = Sc, n = 0 (2), Ln = Y, n = 1 (3)) and monoalkyl species [(NPN(tBu))2Ln(CH2SiMe3)] (Ln = Y (4), Nd (6), Sm (7)). One-pot reaction of [ScCl3(THF)3]/1/MeLi in 1/2/3 eq. ratio gives [(NPN(tBu))2Sc(THF)CH3] 5. Further reaction of 4 with phenylacetylene resulted in the formation of the Y-alkynyl complex [(NPN(tBu))2Y(-C[triple bond, length as m-dash]CPh)] 8. Alkyl abstraction in 2, 3 and 4 by reaction with [PhNMe2H](+)[B(C6F5)4](-) resulted in the formation of cationic alkyl complex ion pairs [(NPN(tBu))Ln(CH2SiMe3)(THF)n](+)[B(C6F5)4](-) (Ln = Sc (9), Y (10)) and [(NPN(tBu))2Y(THF)n](+)[B(C6F5)4](-)11, as confirmed by NMR data. The reaction of bis-NPN alkyl complexes with CHCl3 is the simplest and most reliable protocol to synthesize bis-NPN-chlorido complexes [(NPN(tBu))2Ln-Cl] (Ln = Sc (12), Y (13), Nd (14), Sm (15), Gd (16), Tb (17), Yb (18) and Lu (19)), which can become new post-metallocene alternatives to the prominent organolanthanide building blocks [Cp*2LnX]. Partial hydrolysis of 12 leads to the formation of the oxido/chlorido capped trinuclear complex [{(NPN(tBu))Sc(MU2-Cl)}3(MU3-O)(MU3-Cl)] 20. Molecular structures of 4, 6, 7, 13, 19 and 20 were confirmed by X-ray structure analyses. PMID- 26677969 TI - New drug approvals in acute myeloid leukemia: what's the best end point? PMID- 26677970 TI - Influence of quality of care and individual patient characteristics on quality of life and return to work in survivors of the acute respiratory distress syndrome: protocol for a prospective, observational, multi-centre patient cohort study (DACAPO). AB - BACKGROUND: Health-related quality of life (HRQoL) and return to work are important outcomes in critical care medicine, reaching beyond mortality. Little is known on factors predictive of HRQoL and return to work in critical illness, including the acute respiratory distress syndrome (ARDS), and no evidence exists on the role of quality of care (QoC) for outcomes in survivors of ARDS. It is the aim of the DACAPO study ("Surviving ARDS: the influence of QoC and individual patient characteristics on quality of life") to investigate the role of QoC and individual patient characteristics on quality of life and return to work. METHODS/DESIGN: A prospective, observational, multi-centre patient cohort study will be performed in Germany, using hospitals from the "ARDS Network Germany" as the main recruiting centres. It is envisaged to recruit 2400 patients into the DACAPO study and to analyse a study population of 1500 survivors. They will be followed up until 12 months after discharge from hospital. QoC will be assessed as process quality, structural quality and volume at the institutional level. The main outcomes (HRQoL and return to work) will be assessed by self-report questionnaires. Further data collection includes general medical and ARDS-related characteristics of patients as well as sociodemographic and psycho-social parameters. Multilevel hierarchical modelling will be performed to analyse the effects of QoC and individual patient characteristics on outcomes, taking the cluster structure of the data into account. DISCUSSION: By obtaining comprehensive data at patient and hospital level using a prospective multi-centre design, the DACAPO-study is the first study investigating the influence of QoC on individual outcomes of ARDS survivors. PMID- 26677973 TI - A realist review of family-based interventions for children of substance abusing parents. AB - BACKGROUND: Millions of children across North America and Europe live in families with alcohol or drug abusing parents. These children are at risk for a number of negative social, emotional and developmental outcomes, including an increased likelihood of developing a substance use disorder later in life. Family-based intervention programs for children with substance abusing parents can yield positive outcomes. This study is a realist review of evaluations of family-based interventions aimed at improving psychosocial outcomes for children of substance abusing parents (COSAPs). The primary objectives were to uncover patterns of contextual factors and mechanisms that generate program outcomes, and advance program theory in this field. METHODS: Realist review methodology was chosen as the most appropriate method of systematic review because it is a theory-driven approach that seeks to explore mechanisms underlying program effectiveness (or lack thereof). A systematic and comprehensive search of academic and grey literature uncovered 32 documents spanning 7 different intervention programs. Data was extracted from the included documents using abstraction templates designed to code for contexts, mechanisms and outcomes of each program. Two candidate program theories of family addiction were used to guide data analysis: the family disease model and the family prevention model. Data analysis was undertaken by a research team using an iterative process of comparison and checking with original documents to determine patterns within the data. RESULTS: Programs originating in both the family disease model and the family prevention model were uncovered, along with hybrid programs that successfully included components from each candidate program theory. Four demi-regularities were found to account for the effectiveness of programs included in this review: (1) opportunities for positive parent-child interactions, (2) supportive peer-to-peer relationships, (3) the power of knowledge, and (4) engaging hard to reach families using strategies that are responsive to socio-economic needs and matching services to client lived experience. CONCLUSIONS: This review yielded new findings that had not otherwise been explored in COSAP program research and are discussed in order to help expand program theory. Implications for practice and evaluation are further discussed. PMID- 26677974 TI - Significant role of the choroidal outer layer during recovery from choroidal thickening in Vogt-Koyanagi-Harada disease patients treated with systemic corticosteroids. AB - BACKGROUND: Which of the choroidal layers suffers the most extensive morphological changes during the course of Vogt-Koyanagi-Harada (VKH) disease is still unknown. The aim of this study was to investigate the relationship between total thickness and the thickness of inner or outer layers in the choroid during systemic corticosteroid therapy in patients with VKH disease. METHODS: This retrospective case series included 15 eyes of 10 patients with treatment-naive VKH disease (4 men and 6 women; mean age, 41.4 +/- 14.7 years) received systemic corticosteroid therapy. Whole, inner, and outer choroidal thickness was measured manually at 1 week and at 1 and 3 months after initiation of systemic corticosteroid therapy using enhanced depth imaging optical coherence tomography. The mean thickness values of the layers were compared at each stage. RESULTS: Compared with the 1-week baseline, the mean whole and outer choroidal layer thicknesses were significantly lower at 1 (P = 0.008 and 0.03, respectively) and 3 months (P = 0.008 and 0.02, respectively), whereas the inner layer did not significantly thin. Importantly, there was a significant positive correlation between the rates of change of whole and outer layer thickness from 1 week to 3 months (R = 0.9312, P < 0.0001), but not between the rates of whole and inner layer thickness changes. CONCLUSIONS: The thinning of total choroidal thickness observed after treatment with corticosteroids strongly correlated with outer layer thinning, suggesting that the choroidal outer layer is the primary target in acute-stage VKH disease. PMID- 26677975 TI - Towards breed formation by island model divergence in Korean cattle. AB - BACKGROUND: The main cattle breed in Korea is the brown Hanwoo, which has been under artificial selection within a national breeding program for several decades. Varieties of the Hanwoo known as Jeju Black and Chikso were not included in the breeding program and remained isolated from the effects of recent artificial selection advancements. We analysed the Jeju Black and Chikso populations in regards to their genetic variability, state of inbreeding, as well as level of differentiation from the mainland Hanwoo population. RESULTS: Jeju Black and Chikso were found to have small estimated effective population sizes (N e ) of only 11 and 7, respectively. Despite a small N e , higher than expected heterozygosity levels were observed (0.303 and 0.306), however, lower allelic richness was found for the two island populations (1.76 and 1.77) compared to the mainland population (1.81). The increase in heterozygosity could be due to environmental disease challenges that promoted maintenance of higher genetic variability; however, no direct proof exists. Increased heterozygosity due to a first generation crossing of genetically different populations is not recorded. The differentiation between the Korean populations had F ST values between 0.014 and 0.036 which is not as high as the differentiation within European beef or dairy cattle breeds (0.047-0.111). This suggests that the three populations have not separated into independent breeds. CONCLUSION: Results agree with an island model of speciation where the brown Hanwoo represents the ancestral breed, whilst the Jeju Black and Chikso diverge from this common ancestor, following different evolutionary trajectories. Nevertheless, differences are minor and whether Jeju Black and Chikso cattle will develop into discrete breeds or reintegrate with the main population has to be seen in the future and will largely depend on human management decisions. This offers a rare opportunity to accompany the development of new breeds but also poses challenges on how to preserve these incipient breeds and ensure their long term viability. PMID- 26677976 TI - Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-kappaB Signaling Pathway. AB - Glioblastoma (GBM)-initiating cells (GIC) are a tumorigenic subpopulation that are resistant to radio- and chemotherapies and are the source of disease recurrence. Therefore, the identification and characterization of GIC-specific factors is critical toward the generation of effective GBM therapeutics. In this study, we investigated the role of epithelial V-like antigen 1 (Eva1, also known as myelin protein zero-like 2) in stemness and GBM tumorigenesis. Eva1 was prominently expressed in GICs in vitro and in stem cell marker (Sox2, CD15, CD49f)-expressing cells derived from human GBM tissues. Eva1 knockdown in GICs reduced their self-renewal and tumor-forming capabilities, whereas Eva1 overexpression enhanced these properties. Eva1 deficiency was also associated with decreased expression of stemness-related genes, indicating a requirement for Eva1 in maintaining GIC pluripotency. We further demonstrate that Eva1 induced GIC proliferation through the activation of the RelB-dependent noncanonical NF kappaB pathway by recruiting TRAF2 to the cytoplasmic tail. Taken together, our findings highlight Eva1 as a novel regulator of GIC function and also provide new mechanistic insight into the role of noncanonical NF-kappaB activation in GIC, thus offering multiple potential therapeutic targets for preclinical investigation in GBM. PMID- 26677977 TI - Multikinase Inhibitors Induce Cutaneous Toxicity through OAT6-Mediated Uptake and MAP3K7-Driven Cell Death. AB - The use of multikinase inhibitors (MKI) in oncology, such as sorafenib, is associated with a cutaneous adverse event called hand-foot skin reaction (HFSR), in which sites of pressure or friction become inflamed and painful, thus significantly impacting quality of life. The pathogenesis of MKI-induced HFSR is unknown, and the only available treatment options involve dose reduction or discontinuation of therapy, which have negative effects on primary disease management. To investigate the underlying mechanisms by which sorafenib promotes keratinocyte cytotoxicity and subsequent HFSR induction, we performed a transporter-directed RNAi screen in human epidermal keratinocytes and identified SLC22A20 (OAT6) as an uptake carrier of sorafenib. Further investigations into the intracellular mechanism of sorafenib activity through in situ kinome profiling identified the mitogen-activated protein kinase MAP3K7 (TAK1) as a target of sorafenib that induces cell death. Finally, we demonstrate that sorafenib induced keratinocyte injury in vivo and that this effect could be reversed by cotreatment with the OAT6 inhibitor probenecid. Collectively, our findings reveal a novel pathway that regulates the entry of some MKIs into keratinocytes and explains the basis underlying sorafenib-induced skin toxicity, with important implications for the therapeutic management of HFSR. PMID- 26677979 TI - Primary Care Interventions to Reduce Childhood Obesity in Latino Families. AB - INTRODUCTION: Increasing rates of obesity in Latino children call for culturally sensitive primary care interventions. Despite recent efforts to address this growing disparity, little is known about cultural variables that influence obesity management programs in Latino children. METHODS: A literature search was conducted using CINHAL, Scopus, PubMed, and PsycINFO to review the state of the science regarding primary care interventions to decrease obesity in Latino children. The author analyzed the effects of several cultural practices on obesity and made recommendations based on their clinical implications for weight reduction management programs. RESULTS: Obesity in Latino children is a multifactorial problem influenced by family behaviors, cultural perceptions of weight and health, traditional dietary norms, and socioeconomic status. Current practice lags behind national obesity management recommendations and is further hindered by a lack of consideration of the roles of key cultural differences in Latino families. DISCUSSION: It is imperative to recognize the importance of family preferences and culture when developing weight reduction programs so as to foster long-term behavior changes. More research assessing the efficacy of culturally competent interventions is necessary to guide national efforts to address this increasing disparity. PMID- 26677978 TI - Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis. AB - The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. Effective implementation of personalized medicine will require tools to distinguish actionable genetic alterations within the complex genetic landscape of leukemia. In this study, we performed kinase inhibitor screens to predict functional gene targets in primary specimens from patients with acute myeloid leukemia and chronic myelomonocytic leukemia. Deep sequencing of the same patient specimens identified genetic alterations that were then integrated with the functionally important targets using the HitWalker algorithm to prioritize the mutant genes that most likely explain the observed drug sensitivity patterns. Through this process, we identified tyrosine kinase nonreceptor 2 (TNK2) point mutations that exhibited oncogenic capacity. Importantly, the integration of functional and genomic data using HitWalker allowed for prioritization of rare oncogenic mutations that may have been missed through genomic analysis alone. These mutations were sensitive to the multikinase inhibitor dasatinib, which antagonizes TNK2 kinase activity, as well as novel TNK2 inhibitors, XMD8-87 and XMD16-5, with greater target specificity. We also identified activating truncation mutations in other tumor types that were sensitive to XMD8-87 and XMD16-5, exemplifying the potential utility of these compounds across tumor types dependent on TNK2. Collectively, our findings highlight a more sensitive approach for identifying actionable genomic lesions that may be infrequently mutated or overlooked and provide a new method for the prioritization of candidate genetic mutations. PMID- 26677980 TI - Treatment of actinic cheilitis with methyl aminolevulinate photodynamic therapy and light fractionation: a prospective study of 10 patients. PMID- 26677981 TI - miR-34a inhibits differentiation of human adipose tissue-derived stem cells by regulating cell cycle and senescence induction. AB - MicroRNAs (miRNAs) are critical in the maintenance, differentiation, and lineage commitment of stem cells. Stem cells have the unique property to differentiate into tissue-specific cell types (lineage commitment) during cell division (self renewal). In this study, we investigated whether miR-34a, a cell cycle-regulating microRNA, could control the stem cell properties of adipose tissue-derived stem cells (ADSCs). First, we found that the expression level of miR-34a was increased as the cell passage number was increased. This finding, however, was inversely correlated with our finding that the overexpression of miR-34a induced the decrease of cell proliferation. In addition, miR-34a overexpression decreased the expression of various cell cycle regulators such as CDKs (-2, -4, -6) and cyclins (-E, -D), but not p21 and p53. The cell cycle analysis showed accumulation of dividing cells at S phase by miR-34a, which was reversible by co-treatment with anti-miR-34a. The potential of adipogenesis and osteogenesis of ADSCs was also decreased by miR-34a overexpression, which was recovered by co-treatment with anti-miR-34a. The surface expression of stem cell markers including CD44 was also down-regulated by miR-34a overexpression as similar to that elicited by cell cycle inhibitors. miR-34a also caused a significant decrease in mRNA expression of stem cell transcription factors as well as STAT-3 expression and phosphorylation. Cytokine profiling revealed that miR-34a significantly modulated IL-6 and -8 production, which was strongly related to cellular senescence. These data suggest the importance of miR-34a for the fate of ADSCs toward senescence rather than differentiation. PMID- 26677982 TI - Reporting of consent rates in critical care studies: room for improvement. AB - OBJECTIVES: Reporting of consent rates in published articles is important to determine potential sources of bias and validity and generalizability of results. Our objective was to determine the percentage of critical care studies for which the consent rate was reported. STUDY DESIGN AND SETTING: We reviewed all articles published in eight medical journals in 2013. Studies meeting the following inclusion criteria were selected: (1) randomized controlled trial (RCT) or observational clinical study, (2) study population involving critically ill patients, and (3) part of the study occurring in an intensive care unit. RESULTS: A total of 1,871 articles were screened of which 156 were included. The consent rate was discernable in 30.8% of articles (48/156, 95% confidence interval: 24.1, 38.4) with a median consent rate of 86.9% (interquartile range, 71.6, 94.1). A statement on Research Ethics Board approval was included in 96.8% of studies. There was a significant difference in reporting of consent rates between RCTs and non-RCTs (58.70% vs. 19.09%, P < 0.0001). CONCLUSION: Consent rates are reported in less than one-third of critical care studies. We encourage journals to require reporting of consent rates to improve interpretation, validity, and generalizability of critical care study results. PMID- 26677983 TI - Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology. AB - BACKGROUND & AIMS: Human intestinal crypt-derived enteroids are a model of intestinal ion transport that require validation by comparison with cell culture and animal models. We used human small intestinal enteroids to study neutral Na(+) absorption and stimulated fluid and anion secretion under basal and regulated conditions in undifferentiated and differentiated cultures to show their functional relevance to ion transport physiology and pathophysiology. METHODS: Human intestinal tissue specimens were obtained from an endoscopic biopsy or surgical resections performed at Johns Hopkins Hospital. Crypts were isolated, enteroids were propagated in culture, induced to undergo differentiation, and transduced with lentiviral vectors. Crypt markers, surface cell enzymes, and membrane ion transporters were characterized using quantitative reverse-transcription polymerase chain reaction, immunoblot, or immunofluorescence analyses. We used multiphoton and time-lapse confocal microscopy to monitor intracellular pH and luminal dilatation in enteroids under basal and regulated conditions. RESULTS: Enteroids differentiated upon withdrawal of WNT3A, yielding decreased crypt markers and increased villus-like characteristics. Na(+)/H(+) exchanger 3 activity was similar in undifferentiated and differentiated enteroids, and was affected by known inhibitors, second messengers, and bacterial enterotoxins. Forskolin-induced swelling was completely dependent on cystic fibrosis transmembrane conductance regulator and partially dependent on Na(+)/H(+) exchanger 3 and Na(+)/K(+)/2Cl(-) cotransporter 1 inhibition in undifferentiated and differentiated enteroids. Increases in cyclic adenosine monophosphate with forskolin caused enteroid intracellular acidification in HCO3(-)-free buffer. Cyclic adenosine monophosphate-induced enteroid intracellular pH acidification as part of duodenal HCO3(-) secretion appears to require cystic fibrosis transmembrane conductance regulator and electrogenic Na(+)/HCO3(-) cotransporter 1. CONCLUSIONS: Undifferentiated or crypt-like, and differentiated or villus-like, human enteroids represent distinct points along the crypt-villus axis; they can be used to characterize electrolyte transport processes along the vertical axis of the small intestine. The duodenal enteroid model showed that electrogenic Na(+)/HCO3(-) cotransporter 1 might be a target in the intestinal mucosa for treatment of secretory diarrheas. PMID- 26677985 TI - Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography. AB - BACKGROUND & AIMS: Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis. METHODS: We performed a cross sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques. RESULTS: TE identified patients with fibrosis stage >=2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade >=2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P < .001). Measurement of serum keratin 18 fragments or alanine aminotransferase did not add value to TE or MRI for identifying nonalcoholic steatohepatitis. CONCLUSIONS: MRE and PDFF methods have higher diagnostic performance in noninvasive detection of liver fibrosis and steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757. PMID- 26677986 TI - Increased Risk of Colorectal Cancer Development Among Patients With Serrated Polyps. AB - BACKGROUND & AIMS: Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) are now distinguished from hyperplastic polyps and recognized as precursors to colorectal cancer (CRC). We studied CRC risks associated with serrated polyps. METHODS: By using Danish databases (1977-2009), we conducted a nationwide population-based, case-control study nested within individuals who had received colonoscopies (n = 272,342), and identified 2045 CRC cases and 8105 CRC-free individuals (controls). For each case and control, we identified the first colorectal polyp(s) that underwent a biopsy or were excised during or after the initial colonoscopy, and obtained tissue blocks for hyperplastic lesions. Four expert pathologists reviewed these lesions using current terminology for serrated polyps. We used logistic regression to compute odds ratios (ORs) to associate the risk of CRC with polyp type and estimated the absolute risks by multiplying the risk in patients with no polyps by these ORs. RESULTS: Seventy-nine cases and 142 controls had SSA/Ps (OR, 3.07; 95% confidence interval [CI], 2.30-4.10). SSA/Ps with cytology markers of dysplasia were associated with a particularly high OR (4.76; 95% CI, 2.59-8.73). Women with SSA/P had a higher risk for CRC than men with SSA/P (OR for women, 5.05; 95% CI, 3.05-8.37 vs OR for men, 2.18; 95% CI, 1.24-3.82); patients with SSA/P proximal to the splenic flexure had the highest risk for CRC (OR, 12.42; 95% CI, 4.88 31.58). The OR for CRC was 4.84 in the 14 cases vs 17 controls with TSAs (95% CI, 2.36-9.93), 2.51 in the 757 cases vs 1698 controls with conventional adenomas (95% CI, 2.25-2.80), and 1.30 in the 55 cases vs 235 controls with hyperplastic polyps (95% CI, 0.96-1.77). The 10-year risk for CRC was 4.4% for patients with SSA/P with dysplasia, 4.5% for patients with TSAs, and 2.3% for patients with conventional adenomas. CONCLUSION: Patients with SSA/P or TSA are at increased risk for CRC; their level of risk is similar to or higher than that of patients with conventional adenomas. PMID- 26677987 TI - Initial presentation and outcome of pediatric-onset mixed connective tissue disease: A French multicenter retrospective study. PMID- 26677984 TI - Expression of Activated Ras in Gastric Chief Cells of Mice Leads to the Full Spectrum of Metaplastic Lineage Transitions. AB - BACKGROUND & AIMS: Gastric cancer develops in the context of parietal cell loss, spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM). We investigated whether expression of the activated form of Ras in gastric chief cells of mice leads to the development of SPEM, as well as progression of metaplasia. METHODS: We studied Mist1-CreERT2Tg/+;LSL-K-Ras(G12D)Tg/+ (Mist1 Kras) mice, which express the active form of Kras in chief cells on tamoxifen exposure. We studied Mist1-CreERT2Tg/+;LSL-KRas (G12D)Tg/+;R26RmTmG/+ (Mist1-Kras mTmG) mice to examine whether chief cells that express active Kras give rise to SPEM and IM. Some mice received intraperitoneal injections of the Mitogen activated protein kinase kinase (MEK) inhibitor, selumetinib, for 14 consecutive days. Gastric tissues were collected and analyzed by immunohistochemistry, immunofluorescence, and quantitative polymerase chain reaction. RESULTS: Mist1 Kras mice developed metaplastic glands, which completely replaced normal fundic lineages and progressed to IM within 3-4 months after tamoxifen injection. The metaplastic glands expressed markers of SPEM and IM, and were infiltrated by macrophages. Lineage tracing studies confirmed that the metaplasia developed directly from Kras (G12D)-induced chief cells. Selumetinib induced persistent regression of SPEM and IM, and re-established normal mucosal cells, which were derived from normal gastric progenitor cells. CONCLUSIONS: Expression of activated Ras in chief cells of Mist1-Kras mice led to the full range of metaplastic lineage transitions, including SPEM and IM. Inhibition of Ras signaling by inhibition of MEK might reverse preneoplastic metaplasia in the stomach. PMID- 26677988 TI - Bendamustine conditioning for refractory type I cryoglobulinemia. PMID- 26677989 TI - Is electromagnetic hypersensitivity entirely ascribable to nocebo effects? PMID- 26677990 TI - Coracoid-like osteochondroma and painful giant thoracic bursitis. PMID- 26677991 TI - Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. AB - OBJECTIVE: To evaluate the effect of physiotherapy on functional limitation in an observational cohort of early axial spondyloarthritis. METHODS: DESIGN: prospective population-based cohort study. PATIENTS: 708 patients with early axial spondyloarthritis between 2007 and 2010 naive of TNF blockers. INTERVENTION: early physiotherapy defined by at least eight supervised sessions of physical therapy during the first six months. MEASUREMENTS: the primary outcome was functional improvement defined by a relative improvement of at least 20% in BASFI at six months. Secondary outcomes were improvement in BASFI at one and two years and ASAS20 response criteria at six months. STATISTICAL ANALYSIS: a propensity score of having physiotherapy was developed and multivariate analysis using propensity score weighting were used to assess the effect of physiotherapy on outcome. RESULTS: Overall, 166 (24%) patients had physiotherapy during the first six months. After using propensity score weighting, there was no functional improvement on the primary outcome in patients treated with early physical therapy (relative risk [IC95%]: 1.15 [0.91-1.45]). No differences were observed on secondary outcomes (relative risk [IC95%]: 0.94 [0.80-1.11]). CONCLUSIONS: It seems there is no functional benefit for patients with early spondyloarthritis to be treated early by physiotherapy in daily practice, even though the efficacy of physiotherapy has been shown in several randomized controlled studies. PMID- 26677992 TI - Randomised study versus control group of customised therapeutic education for patients in follow-up for rheumatoid arthritis. AB - OBJECTIVE: We have evaluated customized objectives, predefined during a therapeutic education session for rheumatoid arthritis (RA). METHODS: Fifty-four RA patients were randomised into patient therapeutic education (PTE) group versus waiting list (WL). The final comparative evaluation involved solving 3 predefined problems. RESULTS: Fifty-four were evaluated after 6 months. The main criterion was defined for all three of the chosen themes at 76.9% in the PTE group and 42.4% in the WL group. Among the other positively evaluated criteria were: less corticotherapy, more occupational therapy, more demand for social aid, more physical activity, knowledge of the recognition of an RA attack and how to cope with it. On the other hand, knowledge of the treatments did not differ between the 2 groups nor did the RAPID scores, fatigue, stiffness, depression, compliance, number of consultations and hospitalisations. Patient satisfaction was excellent (between 85.3 and 93.9%). CONCLUSION: This study is a good illustration of the position occupied and value of PTE in solving the problems specific to each RA case, the resulting high level of patient satisfaction and its independently complementary aspects relative to the purely medical treatment of RA. Customized PTE could better respond to specific patients problems in RA. PMID- 26677993 TI - Ankylosing spondylitis self-help organisations - do members differ from non members? AB - OBJECTIVES: Joining a patient self-help organisation is recommended for patients with ankylosing spondylitis (AS). The objective was to compare AS patients who are members of a self-help organisation with non-members regarding disease specific and patient personality aspects, and make inferences on potential benefits of membership. METHODS: A comprehensive questionnaire regarding demographics, smoking habits, acquisition of information about the disease, disease activity, functioning, patient satisfaction, treatment, sick leave, work disability and educational level was distributed to members of the German AS self help organisation and to non-member AS patients. RESULTS: In total, 1273 patients responded. Significant differences regarding age and disease duration led us to match members 2:1 to non-members. In the matched population (n=549), members had a higher level of education, felt more often well-informed about the disease, had less often physically demanding jobs, and smoked less than non-members. Members were more often treated with NSAIDs and less often with TNF-blockers suggesting more severe disease in non-members. While the level of disease activity was similar (BASDAI 4.1 vs. 4.2), members had a better functional status (BASFI 3.5 vs. 3.9) and significantly less days on sick leave during the last year (15.1 days vs. 31.2 days). Days on sick leave increased with increasing BASFI significantly more strikingly in non-members than in members. CONCLUSION: AS patients who are members of an AS self-help organisation have a higher educational level and are much better informed about the disease. Inferences on disease outcome measures, however, are hampered by potential confounders. PMID- 26677994 TI - Patient global assessment in psoriatic arthritis - what does it mean? An analysis of 223 patients from the Psoriatic arthritis impact of disease (PsAID) study. AB - OBJECTIVE: Patient global assessment is a key outcome measure in psoriatic arthritis. To explore the meaning of patient global assessment in psoriatic arthritis by examining associations to domains of health assessed by the Psoriatic arthritis impact of disease score. METHODS: Post-hoc analysis of a multicentre cross-sectional study of patients with psoriatic arthritis. Data collection included patient global assessment, specific joint and skin global patient assessments, Psoriatic arthritis impact of disease questions covering physical (including joints and skin), psychological and social impact, and other comparator outcomes. Univariate analyses (Pearson correlation) and multivariate linear regression were performed to explain patient global assessment and the specific joint and skin global patient assessments. RESULTS: Among 223 patients (mean age: 51.0 [standard deviation, +/-13.3] years; mean disease duration: 9.9 [+/-10.1] years; mean swollen joint count: 4.1 [+/-5.1]; 84.3% with current psoriasis [mainly of less than 5% body surface area]), 50.2% were females. Mean patient global assessment was 4.8 (+/-2.7), mean joint and skin patient assessments were respectively 5.6 (+/-2.5) and 4.1 (+/-3.0). Intraclass correlation between patient global assessment and joint or skin patient assessment was respectively 0.71 (95% confidence interval, 0.64-0.77) and 0.52 (95% confidence interval, 0.42-0.60). In multivariate analyses, patient global assessment was explained (R(2) of model: 0.754) by coping (beta = 0.287); pain (beta = 0.240); work and/or leisure activities (beta = 0.141); and anxiety (beta = 0.109). CONCLUSIONS: Patient global assessment in psoriatic arthritis was explained mainly by physical, but also psychological aspects of the disease. PMID- 26677995 TI - Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis. AB - INTRODUCTION: Cystic fibrosis (CF) is associated with osteoporosis and incident fracture. This study assessed independent predictors of baseline and 2-year changes in bone mineral density (BMD) in adults with CF. METHODS: Sixty-four adult patients with CF, ages 18-57, were recruited from the Massachusetts General Hospital Cystic Fibrosis Care Center. Dual-energy X-ray absorptiometry (DXA) was performed at the spine and radius at baseline and 2 years (in 39 subjects). Estimates of fat-free mass index (FFMI) and fat mass index (FMI) were determined using height, weight, and tetrapolar bioelectric impedance analysis. All subjects completed lung spirometry within 1 month of the study visit. Linear regression models evaluated predictors of baseline BMD Z-scores and change in PA spine BMD Z score over 2 years. Two definitions of low BMD were studied based on Z-score (<= 1.0 and <=-2.0). RESULTS: Low BMD was present in 52% of subjects. Subjects with low BMD were more likely to be male (67% vs. 32%, P=0.009), were more likely to be currently using glucocorticoids (21% vs. 0%, P<0.001), had lower percent body fat (P=0.04), and were more likely to have had a previous fracture (60% vs. 46%, P=0.007). In multivariable models, greater FFMI and height, but not greater FMI, were associated with greater BMD. In multivariable models, low forced vital capacity (FVC) and greater FMI were associated with greater loss of BMD at the PA spine over two years. CONCLUSIONS: Male sex, short stature, and low lean mass are associated with low BMD in CF. Greater adiposity and lower lung function are predictors of negative change in BMD Z-score over 2 years. PMID- 26677997 TI - Choroidal osteoma: Bone in the eye. PMID- 26677996 TI - Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS. AB - OBJECTIVES: Paradoxical tuberculosis (TB) worsening, an example of the immune reconstitution inflammatory syndrome (IRIS), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (TNF) discontinuation during biotherapy-induced TB. To better recognize it, we analyzed the frequency and factors associated with anti-TNF-induced TB-IRIS. METHODS: Case control study on anti-TNF-associated TB patients. IRIS cases, defined with the following consensus criteria, were matched to two controls (anti-TNF-associated TB without IRIS). IRIS frequency was based on the French RATIO registry. Conditional logistic-regression identified IRIS risk factors. RESULTS: Fourteen patients developed anti-TNF-associated TB-IRIS within medians of 45 [IQR 22-131] days after starting anti-TB therapy and 110 [IQR 63-164] days after the last anti TNF infusion. Each case was matched to two controls by year of TB diagnosis. IRIS associated factors were (odds ratio [95% CI]): disseminated TB (11.4 [1.4-92.2], P=0.03), history of Mycobacterium tuberculosis exposure (12.7 [1.6-103.0], P=0.02) and steroid use at the time of TB diagnosis (4.6 [1.2-17.2], P=0.02). The RATIO registry IRIS frequency was 7%. CONCLUSION: After stopping biotherapy, paradoxical anti-TNF-associated TB worsening occurred most often in patients with disseminated TB. Although diagnosis remains difficult, physicians must be aware of IRIS because prolonged anti-TB treatment is not needed but, paradoxically, immunosuppressant reintroduction may be. PMID- 26677998 TI - Low pre-treatment B-cell counts are not a risk factor of infection in patients treated with rituximab for autoimmune diseases: An observational study. AB - OBJECTIVES: Rituximab (RTX) is increasingly used in patients with refractory rheumatoid arthritis (RA) and other severe autoimmune diseases (AID). In practice, many clinicians are reluctant to prescribe RTX in patients with low B cell counts because of the presumed risk of infection. The aim of this study was therefore to investigate whether B-cell counts before treatment or retreatment with RTX predict the occurrence of infections. METHODS: Observational, single centre study of 161 patients treated with RTX for RA and other AID at a tertiary hospital. CD19+ B-cell counts were assessed by flow cytometry and multivariate statistical analysis adjusted for various potential predictors was performed. RESULTS: The rate of severe infection was 5.9/100 patient-years in RA patients and 24.9 in non-RA AID (P<0.001). Low B-cell counts at the time of RTX infusion were not associated with subsequent severe (HR=0.55, P=0.60) or overall infection (HR=0.85, P=0.58). Significant pre-treatment predictors of severe infection were a diagnosis other than RA (HR=4.68, P<0.001), immunoglobulin (Ig) G levels <7g/L (HR=2.36, P=0.01), age (HR=1.03, P=0.01), and diabetes (HR=3.61, P=0.01). CONCLUSIONS: Low B-cell counts before RTX infusion did not predict subsequent infections in this population treated with RTX for RA and other AID, therefore not supporting the practice of pre-treatment assessment of B-cells. Nevertheless, a higher risk of severe infection was confirmed for low pre-treatment IgG levels, older age, diabetes, and AID other than RA. PMID- 26677999 TI - A novel method for a fast diagnosis of septic arthritis using mid infrared and deported spectroscopy. AB - OBJECTIVE: To assess the ability of mid infrared deported spectroscopy to discriminate synovial fluids samples of septic arthritis patients from other causes of joint effusion. METHODS: Synovial fluids obtained from patients with clinically suspected arthritis were collected, analysed and classified according to standard diagnostic procedures as septic or non-septic. A spectroscopic analysis on synovial fluid samples was then performed using a coiled optical fiber made with chalcogenide glass. After a factorial analysis of the normalized spectra and the computation of a Fisher test used to select the most relevant components, a logistic regression model was fitted, allowing to attribute a score between 0 - non-septic -, and 1 - septic. RESULTS: In a first phase, we analysed the synovial fluids from 122 different synovial fluids including 6 septic arthritis among arthritis of various origins. Septic synovial fluids were identified with a sensitivity of 95.8% and a specificity of 93.9% and an AUROC of 0.977. The analysis of an independent set of samples (n=42, including two septic arthritis) gave similar values. CONCLUSIONS: Our data strongly supports the interest of mid infrared deported spectroscopy, which could be used potentially at point of care, for a rapid and easy diagnosis of septic arthritis. Now, the precision of the diagnosis must be evaluated through a multicentric study on a larger panel of patients. PMID- 26678000 TI - Characteristics and management of rheumatoid arthritis in France: Analysis of a representative French national claims database resulting in an estimated prevalence of 0.35. PMID- 26678001 TI - Effects of tumor necrosis factor-alpha inhibitors on new bone formation in ankylosing spondylitis. AB - OBJECTIVES: To better understand the effect of TNF-alpha inhibitors (TNFi) on new bone formation in ankylosing spondylitis (AS) patients. METHODS: We systematically searched the articles in EMBASE and PubMed. RESULTS: Fifteen articles were enrolled. In all the 9 TNFi-treated cohorts, the vertebral corners with inflammatory lesions at baseline were at higher risk to develop new syndesmophytes than those without inflammatory lesions, although a few syndesmophytes also developed at the vertebral corners without inflammatory lesions at baseline. The advanced inflammatory lesions including fat deposition on baseline MRI showed a higher risk for syndesmophyte formation than the acute inflammatory lesions. Because the number of analyzed vertebral corners were too small, it might not be true that new syndesmophytes developed more frequently at the corners with inflammatory lesions completely resolved than those with persistent inflammation after TNFi treatment. Four studies with 2-year follow-up revealed null effect of TNFi on radiographic progression compared with historical controls with lower disease activity, and 3 studies with >=4-year follow-up proved inhibitory effect of TNFi on new bone formation in AS patients. Patients with a delay of >10 years in starting TNFi therapy were more likely to experience radiographic progression as compared to those who started earlier. CONCLUSIONS: In TNFi treated AS patients, baseline inflammation is linked with syndesmophyte development. An earlier initiation of TNFi therapy may slow the radiographic progression in AS, and TNFi may lose its benefit of retarding new bone formation at advanced stage of AS especially after the focal fat infiltration or syndesmophyte formation. PMID- 26678002 TI - Can ARFI elastometry of the salivary glands contribute to the diagnosis of Sjogren's syndrome? AB - OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) rests on a converging set of clinical and laboratory findings. Salivary-gland ultrasonography (SGUS) was recently shown to assist in the diagnosis and therapeutic monitoring of pSS. Our objective here was to measure salivary-gland elasticity using Acoustic Radiation Force Impulse (ARFI) ultrasonography in patients with pSS and to compare the results to those obtained in healthy controls. METHODS: SGUS with ARFI elastometry was performed in 10 patients with pSS and 15 healthy controls. Ten impulses per gland were used for both submandibular and both parotid glands of each participant. Mean shear wave velocity (SWV) in m/s was compared between the patients and controls using the Mann-Whitney U test. RESULTS: For the parotid glands, mean SWV was significantly higher in the pSS group than in the control group (2.335+/-0.315 vs 1.785+/ 0.384, respectively; P=0.001). Mean SWV values for the submandibular glands were not significantly different between the patients and controls (1.812+/-0.308 vs 1.766+/-0.187, respectively; P=0.892). CONCLUSION: ARFI elastometry may contribute to the diagnosis of pSS, as this noninvasive, fast, and inexpensive investigation can demonstrate abnormal architectural changes in the parotid glands. PMID- 26678003 TI - Reduced incidence of Type 1 diabetes and Type 2 diabetes in systemic sclerosis: A nationwide cohort study. AB - OBJECTIVES: The purpose of this study is to investigate whether systemic sclerosis is a risk factor for diabetes. METHODS: From Taiwan's National Health Insurance Research Database and Registry of Catastrophic Illness database, we enrolled patients with systemic sclerosis and controls. Each systemic sclerosis patient was matched to at most three controls by sex, age, month and year of first diagnosis. Standardized incidence ratio (SIR) of diabetes in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). RESULTS: A total of 2671 patients with systemic sclerosis and 7769 controls were enrolled. Patients with systemic sclerosis had decreased type 1 diabetes (SIR: 0.18, 95% CI=0.04-0.82). In female groups, systemic sclerosis patients also had lower rates of incident type 1 diabetes (SIR: 0.21, 95% CI=0.05-0.95). Male and female patients with systemic sclerosis both had lower rates of incident type 2 diabetes (SIR: 0.46, 95% CI=0.29-0.72; SIR: 0.41, 95% CI=0.33-0.51, respectively). Systemic sclerosis patients had decreased type 1 diabetes and type 2 diabetes (HR: 0.18, 95% CI=0.04-0.74; HR: 0.42, 95% CI=0.36-0.50, respectively) after adjusting for age and sex. CONCLUSIONS: The results clearly showed that patients with systemic sclerosis had lower incidence of type 1 diabetes and type 2 diabetes compared to control subjects. PMID- 26678004 TI - Morphometric characteristics of the umbilical cord and vessels in fetal growth restriction and pre-eclampsia. AB - BACKGROUND: Reports on the morphometric analysis of umbilical cord (UC) and its vessels have been inconsistent due to varying inclusion criteria and methodology. The current study tried to overcome the limitations of previous studies by comparing the UC in pregnancies complicated by fetal growth restriction (FGR), preeclampsia (PE) and FGR+PE, to healthy controls. AIMS: Analyze the morphometric attributes of the UC in pregnancies complicated by FGR and PE. STUDY DESIGN: Case control. SUBJECTS: The study groups consisted of 36 patients with FGR+PE, 72 with FGR (without PE) and 15 with PE (without FGR). They were compared to 50 patients without FGR or PE. OUTCOME MEASURES: Histological cross-sections of the UC were photographed and measured. The following variables were recorded: cross-section area of UC, thickness and surface area of umbilical vessel walls, shortest distance between cord surface and nearest artery (DSA), distance between the arteries (DBA) and placental weight and measurements. The area of the Wharton's jelly (WJ) area was calculated. RESULTS: UC and WJ cross-section areas were significantly smaller in FGR+PE and FGR, but not in PE. The umbilical vessel wall area was decreased in FGR+PE, but the thickness was not significantly decreased in all three study groups, compared to controls. DSA was smaller in all three groups, whereas DBA was not significantly different, compared to controls. CONCLUSIONS: Smaller UC cross-section areas were seen in FGR and FGR+PE, but not in PE without FGR. However, there is no evidence to determine whether this reduction is a cause or consequence of FGR. Reduced DSA in PE, whose UC cross section area was not smaller as in FGR and FGR+PE, might reflect alterations in UC induced by PE. PMID- 26678005 TI - How Dynein Moves Along Microtubules. AB - Cytoplasmic dynein, a member of the AAA (ATPases Associated with diverse cellular Activities) family of proteins, drives the processive movement of numerous intracellular cargos towards the minus end of microtubules. Here, we summarize the structural and motile properties of dynein and highlight features that distinguish this motor from kinesin-1 and myosin V, two well-studied transport motors. Integrating information from recent crystal and cryoelectron microscopy structures, as well as high-resolution single-molecule studies, we also discuss models for how dynein biases its movement in one direction along a microtubule track, and present a movie that illustrates these principles. PMID- 26678007 TI - CHADS2 Scores as a Predictor of Ischemic Stroke in Patients With Peripheral Artery Disease. AB - OBJECTIVE: To assess the predictive value of CHADS2 (congestive heart failure, hypertension, age >=75 years, diabetes mellitus, stroke) scores for stroke risk in patients with peripheral artery disease (PAD). PATIENTS AND METHODS: From Taiwan's National Health Insurance Research Database, we identified a total of 479 participants with non-atrial fibrillation PAD diagnoses recorded from January 1, 2002, through December 31, 2009. The CHADS2 score was used to stratify 5-year ischemic stroke risk. All participants were followed up from the date of enrollment until ischemic stroke event, death, or the end of 2009. RESULTS: The 5 year risk of ischemic stroke in the present study was 9.4%. A strong correlation was found between the PAD and CHADS2 score (CHADS2 score of 0-1, 0.4%; CHADS2 score of 2-3, 12.3%; CHADS2 score >=4, 84.0%; area under the curve = 0.920). After adjustment, CHADS2 score was found to be positively correlated with increased risk of ischemic stroke. CONCLUSIONS: Our results indicate that patients with PAD have a significantly higher risk of ischemic stroke and that the CHADS2 score can be used as an indicator of risk for ischemic stroke. Cardiovascular risk evaluation and management are suggested for patients with PAD and higher CHADS2 scores. PMID- 26678006 TI - Personalizing Aspirin Use for Targeted Breast Cancer Chemoprevention in Postmenopausal Women. AB - OBJECTIVE: To evaluate the association of aspirin and other nonsteroidal anti inflammatory drugs with the incidence of postmenopausal breast cancer for risk subgroups defined by selected nonmodifiable or difficult to modify breast cancer risk factors in order to better understand the potential risk-benefit ratio for targeted chemoprevention. PATIENTS AND METHODS: Postmenopausal women with no history of cancer on July 1, 1992 (N=26,580), were prospectively followed up through December 31, 2005, for breast cancer incidence (N=1581). Risk subgroups were defined on the basis of family history of breast cancer, age at menarche, age at menopause, parity/age at first live birth, personal history of benign breast disease, and body mass index. Hazard ratios (HRs) and 95% CIs adjusted for other breast cancer risk factors were estimated using Cox models. RESULTS: Aspirin use was associated with a lower incidence of breast cancer for women with a family history of breast cancer (HR, 0.62 for 6 or more times per week vs never use; 95% CI, 0.41-0.93) and those with a personal history of benign breast disease (HR, 0.69; 95% CI, 0.50-0.95) but not for women in higher-risk subgroups for age at menarche, age at menopause, parity/age at first live birth, or body mass index. In contrast, inverse associations with aspirin use were observed in all lower-risk subgroups. Nonsteroidal anti-inflammatory drug use had no association with breast cancer incidence. CONCLUSION: On the basis of their increased risk of breast cancer, postmenopausal women with a family history of breast cancer or a personal history of benign breast disease could potentially be targeted for aspirin chemoprevention studies. Future studies are needed to confirm these findings. PMID- 26678008 TI - PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. AB - BACKGROUND & AIMS: Risk scores for hepatocellular carcinoma (HCC) developed in Asians offer poor-moderate predictability in Caucasian patients with chronic hepatitis B (CHB). This nine center cohort study aimed to develop and validate an accurate HCC risk score in Caucasian CHB patients treated with the current oral antivirals, entecavir/tenofovir. METHODS: We included 1815 adult Caucasians with CHB and no HCC at baseline who received entecavir/tenofovir for ?12 months. Using data from eight centers (derivation dataset, n=1325), a HCC risk score was developed based on multivariable Cox models and points system for simplification. Harrell's c-index was used as discrimination, bootstrap for internal validation and the data from the 9(th) and largest center (validation dataset, n=490) for external validation. RESULTS: The 5-year cumulative HCC incidence rates were 5.7% and 8.4% in the derivation and validation dataset, respectively. In the derivation dataset, age, gender, platelets and cirrhosis were independently associated with HCC. The PAGE-B score was developed based on age, gender and platelets (c-index=0.82, 0.81 after bootstrap validation). The addition of cirrhosis did not substantially improve the discrimination (c-index=0.84). The predictability of PAGE-B score was similar (c-index=0.82) in the validation dataset. Patients with PAGE-B ?9, 10-17, ?18 had 5-year cumulative HCC incidence rates of 0%, 3%, 17% in the derivation and 0%, 4%, 16% in the validation dataset. CONCLUSION: PAGE-B, which is based only on baseline patients' age, gender and platelets, represents a simple and reliable score for prediction of the 5-year HCC risk in Caucasian CHB patients under entecavir/tenofovir. PMID- 26678010 TI - Association of four new candidate genetic variants with Parkinson's disease in a Han Chinese population. AB - Large-scale meta-analysis of genome-wide association data has identified six new risk loci (SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C, and DDRGK1) for Parkinson's disease (PD). However, the characteristics of those loci in a Han Chinese population from mainland China are unknown. We examined genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 with PD susceptibility in a Han Chinese population of 1028 sporadic PD patients and 1109 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, we did not observe any significant difference in genotype distribution between PD patients and controls for the four loci, even after being stratified by age at onset. Besides, minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our findings first demonstrated that VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 do not confer a significant risk for PD in Chinese population. Additional replication studies in other populations and functional studies are warranted to better validate the role of the four new loci in PD risk. PMID- 26678009 TI - Translational control of nociception via 4E-binding protein 1. AB - Activation of the mechanistic/mammalian target of rapamycin (mTOR) kinase in models of acute and chronic pain is strongly implicated in mediating enhanced translation and hyperalgesia. However, the molecular mechanisms by which mTOR regulates nociception remain unclear. Here we show that deletion of the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a major mTOR downstream effector, which represses eIF4E activity and cap-dependent translation, leads to mechanical, but not thermal pain hypersensitivity. Mice lacking 4E-BP1 exhibit enhanced spinal cord expression of neuroligin 1, a cell adhesion postsynaptic protein regulating excitatory synapse function, and show increased excitatory synaptic input into spinal neurons, and a lowered threshold for induction of synaptic potentiation. Pharmacological inhibition of eIF4E or genetic reduction of neuroligin 1 levels normalizes the increased excitatory synaptic activity and reverses mechanical hypersensitivity. Thus, translational control by 4E-BP1 downstream of mTOR effects the expression of neuroligin 1 and excitatory synaptic transmission in the spinal cord, and thereby contributes to enhanced mechanical nociception. PMID- 26678011 TI - Ultrasonic Treatment Enhanced Ammonia-Oxidizing Bacterial (AOB) Activity for Nitritation Process. AB - Oxidation of ammonia to nitrite rather than nitrate is critical for nitritation process for wastewater treatment. We proposed a promising approach by using controlled ultrasonic treatment to enhance the activity of ammonia-oxidizing bacteria (AOB) and suppress that of nitrite-oxidizing bacteria (NOB). Batch activity assays indicated that when ultrasound was applied, AOB activity reached a peak level and then declined but NOB activity deteriorated continuously as the power intensity of ultrasound increased. Kinetic analysis of relative microbial activity versus ultrasonic energy density was performed to investigate the effect of operational factors (power, sludge concentration, and aeration) on AOB and NOB activities and the test parameters were selected for reactor tests. Laboratory sequential batch reactor (SBR) was further used to test the ultrasonic stimulus with 8 h per day operational cycle and synthetic waste urine as influent. With specific ultrasonic energy density of 0.09 kJ/mg VSS and continuously fed influent containing above 200 mg NH3-N/L, high AOB reproductive activity was achieved and nearly complete conversion of ammonia-N to nitrite was maintained. Microbial structure analysis confirmed that the treatment changed community of AOB, NOB, and heterotrophs. Known AOB Nitrosomonas genus remained at similar level in the biomass while typical NOB Nitrospira genus disappeared in the SBR under ultrasonic treatment and after the treatment was off for 30 days. PMID- 26678012 TI - Tunable Photothermal Actuators Based on a Pre-programmed Aligned Nanostructure. AB - For various applications, it is challenging but essential to obtain complex tunable mechanical actuations in response to environmental stimuli. Here, a general and effective strategy is developed to produce multiple types of photomechanical actuation (from phototropic/apheliotropic bending to three dimensional helical buckling) by manipulating the orientation of one-dimensional nanomaterials. These materials are manipulated to mimic plants that generate diverse mechanical motions through the orientation of cellulose fibrils. The photomechanical actuations can be completed in milliseconds and can be performed reversibly without detectable fatigue after 100 000 cycles. This capacity to produce multiple types of photomechanical actuation is further developed to produce complex integrated movements, as demonstrated by a light-manipulated robotic arm and a solar energy harvesting system. PMID- 26678013 TI - Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo. AB - The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR 7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848. PMID- 26678014 TI - Plasma cholinesterase activity as a biomarker for quantifying exposure of green sturgeon to carbaryl following applications to control burrowing shrimp in Washington State. AB - Willapa Bay (Washington State, USA) has been 1 of the rare intertidal locations where large-scale pesticide applications occur. Until recently, carbaryl was applied to control burrowing shrimp that decrease commercial oyster productivity. The bay is a critical habitat for green sturgeon (Acipenser medirostris), an anadromous species listed as threatened under the US Endangered Species Act. However, the hazard that carbaryl poses is unknown. Surrogate seawater-acclimated white sturgeon (A. transmontanus) were exposed to 0 MUg L(-1) , 30 MUg L(-1) , 100 MUg L(-1) , 300 MUg L(-1) , 1000 MUg L(-1) , and 3000 MUg L(-1) carbaryl for 6 h, and brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) activities were measured. Enzyme recovery was measured in an additional cohort exposed to 1000 MUg L(-1) carbaryl for 6 h. Activity of AChE was reduced (p <= 0.001) at concentrations >= 100 MUg L(-1) with recovery in the 1000 MUg L( 1) cohort by 72 h. Surprisingly, BChE activity was greater than controls at concentrations >= 300 MUg L(-1) (p > 0.05), a finding confirmed in additional fish exposed to 3000 MUg L(-1) for 6 h (+30%, p < 0.001) with apparent recovery by 48 h. Plasma samples were collected from free-living green sturgeon before and 4 d to 5 d after application of carbaryl in Willapa Bay. Activity of BChE after application was reduced 28% (p < 0.001), indicating exposure to the pesticide. However, the lack of congruence between BChE and AChE activity in captive white sturgeon exposed to carbaryl indicates that further studies are needed to better understand the risk carbaryl exposure poses to green sturgeon. Environ Toxicol Chem 2016;35:2003-2015. (c) 2015 SETAC. PMID- 26678015 TI - Effects of CYP3A Modulators on the Pharmacokinetics of Naloxegol. AB - Naloxegol, a peripherally acting MU-opioid receptor antagonist, was recently approved in the United States for the treatment of opioid-induced constipation. This study evaluated the effects of CYP3A inhibition and induction on the pharmacokinetics, safety, and tolerability of naloxegol. Separate open-label, nonrandomized, fixed-sequence, 3-period, 3-treatment, crossover studies of naloxegol (25 mg by mouth [PO]) in the absence or presence of the inhibitors ketoconazole (400 mg PO) and diltiazem extended release (240 mg PO), or the inducer rifampin (600 mg PO) were conducted in healthy volunteers. Area under the curve (AUCinfinity ) for naloxegol was increased with coadministration of either ketoconazole (12.9-fold) or diltiazem (3.4-fold) and decreased by 89% with coadministration of rifampin compared with AUCinfinity for naloxegol alone. Naloxegol was generally safe and well tolerated when given alone or coadministered with the respective CYP3A modulators; 1 subject discontinued because of elevations in liver enzymes attributed to rifampin. The exposure of naloxegol was affected substantially by ketoconazole, diltiazem, and rifampin, suggesting that it is a sensitive in vivo substrate of CYP3A4. PMID- 26678016 TI - Attenuated presenilin-1 endoproteolysis enhances store-operated calcium currents in neuronal cells. AB - Presenilins have been reported to regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer's disease (AD). Reduced endoproteolysis levels of presenilin-1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. This study deals with the effect of attenuated endoproteolysis of PS1 on store-operated calcium (SOC) entry in neuronal cells and mouse fibroblasts with double knockouts of PS1 and PS2. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The increase in SOC entry was not accompanied by any changes in protein levels of channels subunits or stromal interaction molecule. These data are important for understanding the role of PS1 in AD, apart from its involvement in gamma secretase cleavage of amyloid precursor protein into Abeta. Taking into account that most of familial AD-connected mutations in PS1 are loss-of-function, the observed effects may well be general for familial AD. Reduced endoproteolysis levels of presenilin-1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The data obtained shed light on Alzheimer's disease pathogenesis and implicates to the future drugs development. PMID- 26678017 TI - Pulmonary function and fitness years after treatment for hypersensitivity pneumonitis during childhood. AB - BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated diffuse lung disease. Significant improvement in lung function and diffusing capacity after treatment was previously demonstrated, while long-term data focusing specifically on peripheral airway impairment and peak oxygen uptake (fitness) are lacking. Hence, the aim of this study was to conduct a comprehensive study to determine the stability of pulmonary function and fitness in patients previously diagnosed with HP. METHODS: We performed a cross-sectional follow-up study with inclusion of longitudinal data if available in patients previously diagnosed with biopsy and high-resolution computed tomography-verified HP during childhood. We performed multiple breath wash-out (LCI2.5 ), spirometry (FEV1 ), bronchiodilator responsiveness test, diffusing capacity (DLCO and DLCO /VA ), body plethysmography (TLC), and peak oxygen uptake (VO2peak ). St. George Respiratory Questionnaire was used as a measure of respiratory quality of life. RESULTS: Twenty two patients were assessed. LCI2.5 was abnormal in 47.4% compared to abnormal FEV1 in only 9.1% and without significant bronchiodilator responsiveness. DLCO and TLC were abnormal in 40.9 and 13.6%, respectively, while DLCO /VA was within normal range. Only 11.1% demonstrated abnormal VO2peak . All longitudinally assessed outcomes remained unchanged between end of treatment and time of follow up. CONCLUSIONS: A large proportion of patients previously diagnosed with HP had abnormal LCI2.5 in contrast to normal spirometry. Spirometric outcomes, TLC, and diffusing capacity were persistently slightly reduced, but stable, and VO2peak was excellent at time of follow-up. Long-term prognosis in children with HP appears favorable although persistent peripheral airway involvement of unknown clinical significance was demonstrated in almost half of the patients. Pediatr Pulmonol. 2016;51:830-837. (c) 2015 Wiley Periodicals, Inc. PMID- 26678018 TI - Serum hepatitis B core-related antigen as a treatment predictor of pegylated interferon in patients with HBeAg-positive chronic hepatitis B. AB - BACKGROUND & AIMS: The role of quantitative serum hepatitis B core-related antigen (HBcrAg) in patients with chronic hepatitis B (CHB) receiving pegylated interferon (PEG-IFN) is unclear. This study was aimed at comparing its usefulness with quantitative HBsAg in patients with HBeAg-positive CHB receiving PEG-IFN therapy. METHODS: A total 46 patients treated with PEG-IFN for 48 weeks were retrospectively analysed. Intrahepatic covalently closed circular DNA (cccDNA) from paired liver biopsies and serial serum HBsAg and HBcrAg during therapy were assessed. RESULTS: Virological response (VR), defined as HBeAg clearance and HBV DNA <2000 IU/ml at 24 weeks post treatment, was achieved in 15 (32.6%) patients. Responders had significantly higher cccDNA decline from baseline compared with non-responders. Baseline HBsAg and HBcrAg were correlated with cccDNA (r = 0.424, P = 0.020 and r = 0.564, P = 0.001, respectively), and changes in the corresponding markers during therapy were correlated with cccDNA reduction (r = 0.579, P = 0.001 and r = 0.503, P = 0.005, respectively). Responders showed more rapid decline of both markers during therapy compared with non-responders. In multivariate analysis, serum HBcrAg at week 12 was identified as a predictor of VR. The optimal cut-off value for HBcrAg (log10 8.0 U/ml) provided negative predictive value (NPV) of achieving VR at weeks 12 and 24 of 94.4 and 100%, respectively, while using HBsAg > 20 000 IU/ml provided NPV of 80 and 100% respectively. CONCLUSIONS: The convenient quantitative HBcrAg represented a reliable marker of intrahepatic cccDNA. Monitoring HBcrAg levels during PEG-IFN therapy may help identify patients with a very low probability of response comparable to, if not better than, quantitative HBsAg. PMID- 26678020 TI - Prevalence of celiac disease in Asia: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: Celiac disease (CD) is emerging in Asia. While a few population-based studies from Asia have reported a prevalence of CD from 0.1% to 1.3%, the exact prevalence of CD in Asia is not known. We conducted a systematic review and meta-analysis to estimate the prevalence of CD in Asia. METHODS: On search of literature, we found 1213 articles, of which 18 articles were included. Diagnosis of CD was based on European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. RESULTS: Pooled sero-prevalence of CD in Asia was 1.6% in 47 873 individuals based on positive anti-tissue transglutaminase and/or anti-endomysial antibodies. Pooled prevalence of biopsy proven CD in Asia was 0.5% in 43 955 individuals. The prevalence of CD among women was higher than in men (0.5% vs 0.4%, P = 0.04). The pooled prevalence of CD was 0.3% in Iran, 0.5% in Turkey, 0.6% in India, and 0.7% in Israel. The pooled prevalence of CD was significantly higher in Israel and India as compared with that in Iran. CONCLUSIONS: Celiac disease is not uncommon in Asia, and the sero-prevalence and prevalence of CD in Asia are 1.6% and 0.5%, respectively. The prevalence of CD varies with gender and geographic location. There is a need for population-based prevalence studies in many Asian countries to properly estimate the burden of CD in Asia. PMID- 26678019 TI - Evaluation of Canine Pancreas-Specific Lipase Activity, Lipase Activity, and Trypsin-Like Immunoreactivity in an Experimental Model of Acute Kidney Injury in Dogs. AB - BACKGROUND: Diagnosis of pancreatitis in dogs is complicated by extrapancreatic disorders that can alter the results of laboratory tests. Extrapancreatic disorders can also affect the diagnosis of exocrine pancreatic insufficiency (EPI). The effects of acute kidney injury (AKI) on pancreas-specific lipase activity (Spec cPL((r)) Test), serum lipase activity and trypsin-like immunoreactivity (TLI) in dogs have not been evaluated. HYPOTHESIS/OBJECTIVES: Serum Spec cPL, lipase activity, and TLI concentrations will increase secondary to decreased kidney function. ANIMALS: Five purpose-bred dogs. METHODS: Experimental prospective study. Gentamicin was used to induce AKI in 5 purpose bred dogs. Serum samples were collected for measurement of creatinine, Spec cPL, lipase activity and TLI over 60 days, during both induction of, and recovery from, AKI. RESULTS: All dogs developed and recovered from AKI. Six of 52 (12%) serum Spec cPL concentrations were increased (2 in the equivocal zone and 4 consistent with pancreatitis) in 2 of 5 (40%) dogs. Two of 51 (4%) serum lipase activity values were increased in 2 of 5 dogs. Serum TLI was increased above the reference range in 17 of 50 (34%) samples in 3 of 5 dogs. For all biomarkers, there was no consistent correlation with increases in serum creatinine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased renal excretion during experimental AKI did not cause consistent and correlated increases in serum Spec cPL, lipase activity, or TLI in this cohort of dogs. PMID- 26678021 TI - Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes. AB - BACKGROUND: Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyposis (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively. METHODS: A prospective prevalence study of adult CRS patients was conducted over a 1-year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyposis (CRSsNP), or AFRS. Patients were administered the Asthma Screening Questionnaire (ASQ) and asthma was confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi square analysis was performed to compare the asthma prevalence among the CRS subtypes. RESULTS: A total of 410 patients (age 48.1 +/- 16.4; 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi square analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS (p = 0.0016) and CRSwNP and CRSsNP (p = 0.0000), but no significant difference between CRSsNP and AFRS (p = 0.2380). CONCLUSION: There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway. PMID- 26678022 TI - Insulin resistance is associated with skeletal muscle weakness in COPD. AB - BACKGROUND AND OBJECTIVE: Quadriceps weakness is seen across all GOLD stages of COPD and is associated with increased morbidity and mortality. As quadriceps weakness is only weakly associated with FEV1 , mechanisms other than airflow obstruction are implicated. We tested the hypothesis that insulin resistance contributes to skeletal muscle weakness in people with stable COPD. METHODS: Fifty-one COPD patients (no exacerbations preceding 6 weeks, no rehabilitation preceding 3 months) without known diabetes mellitus underwent assessment of skeletal muscle, including measurement of quadriceps maximal voluntary contraction (QMVC). Physical activity was measured for 7 days using a multisensory biaxial accelerometer armband. Insulin resistance (HOMA2 IR) was calculated from fasting blood glucose and insulin concentrations. RESULTS: QMVC was 30 +/- 13 kg (74 +/- 25% predicted) and 16 (31%) participants had quadriceps weakness. There was a negative univariate correlation between HOMA2 IR and QMVC (r = -0.446, P = 0.002). HOMA2 IR was greater in people with quadriceps weakness (1.59 +/- 0.99) than in those without (1.11 +/- 0.55, P = 0.032). On multivariate analysis, with age, sex, weight, BODE index and step count per day included in the model, a one-unit increase in insulin resistance was associated with a 5.9 (2.0-9.8)-kg decrease in QMVC (P = 0.004) and a 4.2 (1.3-14.3)-fold increased risk of quadriceps weakness (P = 0.02). CONCLUSION: Insulin resistance is associated with skeletal muscle weakness in COPD, independent of potential confounders. Further studies are required to explore underlying mechanisms and determine whether insulin-sensitizing drugs could augment pulmonary rehabilitation in building skeletal muscle strength in COPD. PMID- 26678026 TI - A taxonomy of estimands for regulatory clinical trials with discontinuations. AB - The National Research Council Panel on Handling Missing Data in Clinical Trials recommended that protocols for clinical trials 'explicitly define... causal estimands of primary interest'. In discussions with sponsors of clinical trials since the publication of the National Research Council report, the expression causal estimands has been the subject of confusion. It may not be entirely clear what the National Research Council panel meant, and in any case, it has not been clear how this recommendation might be put in practice. This paper's purpose is to say how the working group understands it and how we think it should be put in practice. We classify possible choices of estimand according to their usefulness for regulatory purposes in various clinical settings. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26678027 TI - A Study of Excitation Delocalization/Localization in Multibranched Chromophores by Using Fluorescence Excitation Anisotropy Spectroscopy. AB - We describe a simple approach to study the excitation localization/delocalization in multibranched chromophores by using fluorescence excitation anisotropy spectroscopy at room temperature. As examples, the electronic excitations in three different multibranched chromophores (dimers) are investigated. For a weakly coupled dimer, fluorescence anisotropy is independent of excitation wavelength, due to localized excitation as well as the degenerate electronic excited states. In contrast, in the case of a strongly coupled dimer, owing to excitonic splitting, a redistribution of the excitation energy is demonstrated by the dependence of anisotropy spectra on the excitation wavelength, which leads to significant deviation from the anisotropy signal of localized excitation. In particular, based on the law of additivity for anisotropy, the degree of delocalized excitation can be simply estimated for a given dimer. PMID- 26678029 TI - The complete mitochondrial genome of Eumeces chinensis (Squamata: Scincidae) and implications for Scincidae taxonomy. AB - Chinese skink (Eumeces chinensis) is a ground-dwelling oviparous sincid lizard, which is widely distributed in the southern Provinces of China, including Taiwan and Hainan. Here, the complete mitochondrial genome of E. chinensis (17 175 bp in length) has been analyzed for building the database. It contains 37 genes (13 protein-coding genes, 2 rRNA genes and 22 tRNA genes) and a non-coding region (D loop). Overall base composition of the complete mitochondrial DNA is A (32.1%), G (14.3%), C (28.8%), and T (24.8%), so the percentage of A and T (56.9%) is slightly higher than G and C (43.1%). All the genes in E. chinensis were distributed on the H-strand, except for the ND6 subunit gene and nine tRNA genes which were encoded on the L-strand. Our phylogeny study shows that E. chinensis and P. egregius are the sister group which belongs to the genus, Plestiodon. In addition, we also prove that Lacertidae is sister to the families, Gekkonidae and Scincidae. PMID- 26678030 TI - Real-time feedback from iterative electronic structure calculations. AB - Real-time feedback from iterative electronic structure calculations requires to mediate between the inherently unpredictable execution times of the iterative algorithm used and the necessity to provide data in fixed and short time intervals for real-time rendering. We introduce the concept of a mediator as a component able to deal with infrequent and unpredictable reference data to generate reliable feedback. In the context of real-time quantum chemistry, the mediator takes the form of a surrogate potential that has the same local shape as the first-principles potential and can be evaluated efficiently to deliver atomic forces as real-time feedback. The surrogate potential is updated continuously by electronic structure calculations and guarantees to provide a reliable response to the operator for any molecular structure. To demonstrate the application of iterative electronic structure methods in real-time reactivity exploration, we implement self-consistent semiempirical methods as the data source and apply the surrogate-potential mediator to deliver reliable real-time feedback. PMID- 26678028 TI - Biomedical applications of nisin. AB - Nisin is a bacteriocin produced by a group of Gram-positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized from mRNA and the translated peptide contains several unusual amino acids due to post-translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is FDA approved and generally regarded as a safe peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. Studies have reported that nisin can prevent the growth of drug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram-positive and Gram-negative disease-associated pathogens. Nisin has been reported to have anti-biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host-defence peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumours and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications. PMID- 26678031 TI - MicroRNA-708-5p acts as a therapeutic agent against metastatic lung cancer. AB - MicroRNAs (miRNAs) have recently been recognized as targets for anti-metastatic therapy against cancer malignancy. Development of effective miRNA mediated therapies remains a challenge to both basic research and clinical practice. Here we presented the evidence for a miR-708-5p mediated replacement therapy against metastatic lung cancer. Expression of miR-708-5p was substantially reduced in metastatic lung cancer samples and cancer cell lines when compared to non metastatic counterparts. Expression of the miRNA suppressed cell survival and metastasis in vitro through its direct target p21, and inhibited the PI3K/AKT pathway and stem cell-like characteristics of lung cancer cells. Systemic administration of this miRNA in a mouse model of NSCLC using polyethylenimine (PEI)-mediated delivery of unmodified miRNA mimics induced tumor specific apoptosis. It also effectively protected the tested animals from developing metastatic malignancy without causing any observed toxicity. The findings strongly support miR-708-5p as a novel and effective therapeutic agent against metastatic malignancy of non-small cell lung cancer. PMID- 26678032 TI - Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour. AB - Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of gammaH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID- 26678033 TI - Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade. AB - Intrinsic cross-resistance to inhibition of different signaling pathways may hamper development of combinatorial treatments in melanoma, but the relative frequency of this phenotype and the strategies to overcome this hurdle remain poorly understood. Among 49 BRAF-mutant melanoma cell lines from patients not previously treated with target therapy, 21 (42.9%) showed strong primary resistance (IC50 > 1 MUM) to a BRAFV600E inhibitor. Most of the BRAF-inhibitor resistant cell lines showed also strong or intermediate cross-resistance to MEK1/2- and to PI3K/mTOR-specific inhibitors. Primary cross-resistance was confirmed in an independent set of 23 BRAF-mutant short-term melanoma cell cultures. MEK1/2 and PI3K/mTOR co-targeting was the most effective approach, compared to BRAF and PI3K/mTOR dual blockade, to counteract primary resistance to BRAF inhibition and the cross-resistant phenotype. This was shown by extensive drug interaction analysis, tumor growth inhibition assays in-vivo, p-ERK and p AKT inhibition, promotion of melanoma apoptosis, apoptosis-related protein modulation, activation of effector caspases and selective modulation of genes involved in melanoma drug resistance and belonging to the ERK/MAPK and PI3K/AKT canonical pathways. Compared to co-targeting of mutant BRAF and PI3K/mTOR, the association of a MEK1/2 and a PI3K/mTOR inhibitor was more effective in the activation of Bax and of caspase-3 and in the induction of caspase-dependent melanoma apoptosis. Furthermore Bax silencing reduced the latter effects. These results suggest that intrinsic resistance to BRAF inhibition is frequently associated with primary cross-resistance to MEK and PI3K/mTOR blockade in BRAF mutant melanoma and provide pre-clinical evidence for a combinatorial approach to counteract this phenotype. PMID- 26678034 TI - Identification of a novel RNA giant nuclear body in cancer cells. AB - Constitutive synthesis of oncogenic mRNAs is essential for maintaining the uncontrolled growth of cancer cells. However, little is known about how these mRNAs are exported from the nucleus to the cytoplasm. Here, we report the identification of a RNA giant nuclear body (RNA-GNB) that is abundant in cancer cells but rare in normal cells. The RNA-GNB contains a RNA core surrounded by a protein shell. We identify 782 proteins from cancer-associated RNA-GNBs, 40% of which are involved in the nuclear mRNA trafficking. RNA-GNB is required for cell proliferation, and its abundance is positively associated with tumor burden and outcome of therapies. Our findings suggest that the RNA-GNB is a novel nuclear RNA trafficking organelle that may contribute to the nuclear mRNA exporting and proliferation of cancer cells. PMID- 26678035 TI - Prognostic significance of FAM83D gene expression across human cancer types. AB - The family with sequence similarity 83, member D (FAM83D) gene has been proposed as a new prognostic marker for breast cancer. Here we further evaluate the prognostic significance of FAM83D expression in different breast cancer subtypes using a meta-analysis. Patients with higher FAM83D mRNA levels have significantly decreased overall and metastatic relapse-free survival, particularly in the group of patients with ER-positive, or luminal subtype tumors. We also assessed FAM83D alterations and its prognostic significance across 22 human cancer types using The Cancer Genome Atlas (TCGA). FAM83D is frequently gained in the majority of human cancer types, resulting in the elevated expression of FAM83D. Higher levels of FAM83D mRNA expression are significantly associated with decreased overall survival in several cancer types. Finally, we demonstrate that TP53 mutation in human cancers is coupled to a significant increase in the expression of FAM83D, and that a higher level of FAM83D expression is positively correlated with an increase in genome instability in many cancer types. These results identify FAM83D as a potential novel oncogene across multiple human cancer types. PMID- 26678036 TI - Optimizing Antibiotic Dosing Strategies for the Treatment of Gram-negative Infections in the Era of Resistance. AB - Gram-negative organisms are an increasing source of concern within the healthcare setting due to their common presence as a cause of infection and emerging resistance to current therapies. However, current antimicrobial dosing recommendations may be insufficient for the treatment of gram-negative infections. Applying knowledge of an antibiotic's pharmacokinetic/pharmacodynamic profile when designing a dosing regimen leads to a greater likelihood of achieving optimal exposure, including against gram-negative pathogens with higher MICs. Additionally, administering antibiotics directly to the site of infection, such as via aerosolization for pneumonia, is another method to achieve optimized drug exposure at the site of infection. Incorporating these treatment strategies into clinical practice will assist antimicrobial stewardship programs in successfully treating gram-negative infections. PMID- 26678037 TI - Potential targets of VIVIPAROUS1/ABI3-LIKE1 (VAL1) repression in developing Arabidopsis thaliana embryos. AB - Developing Arabidopsis seeds accumulate oils and seed storage proteins synthesized by the pathways of primary metabolism. Seed development and metabolism are positively regulated by transcription factors belonging to the LAFL (LEC1, AB13, FUSCA3 and LEC2) regulatory network. The VAL gene family encodes repressors of the seed maturation program in germinating seeds, although they are also expressed during seed maturation. The possible regulatory role of VAL1 in seed development has not been studied to date. Reverse genetics revealed that val1 mutant seeds accumulated elevated levels of proteins compared with the wild type, suggesting that VAL1 functions as a repressor of seed metabolism; however, in the absence of VAL1, the levels of metabolites, ABA, auxin and jasmonate derivatives did not change significantly in developing embryos. Two VAL1 splice variants were identified through RNA sequencing analysis: a full length form and a truncated form lacking the plant homeodomain-like domain associated with epigenetic repression. None of the transcripts encoding the core LAFL network transcription factors were affected in val1 embryos. Instead, activation of VAL1 by FUSCA3 appears to result in the repression of a subset of seed maturation genes downstream of core LAFL regulators, as 39% of transcripts in the FUSCA3 regulon were derepressed in the val1 mutant. The LEC1 and LEC2 regulons also responded, but to a lesser extent. Additional 832 transcripts that were not LAFL targets were derepressed in val1 mutant embryos. These transcripts are candidate targets of VAL1, acting through epigenetic and/or transcriptional repression. PMID- 26678038 TI - Species differences in metabolism of ripasudil (K-115) are attributed to aldehyde oxidase. AB - 1. We examined the metabolism of ripasudil (K-115), a selective and potent Rho associated coiled coil-containing protein kinase (ROCK) inhibitor, by in vitro and in vivo studies. 2. First, we identified metabolites and metabolic enzymes involved in ripasudil metabolism. Species differences were observed in metabolic clearance and profiles of metabolites in liver S9 fraction and hepatocytes. In addition, ripasudil was metabolised in humans and monkey S9 without nicotinamide adenine dinucleotide phosphate (NADPH). Studies using specific inhibitors and human recombinant enzyme systems showed that M1 (main metabolite in humans) formation is mediated by aldehyde oxidase (AO). 3. Therefore, we developed ripasudil as an ophthalmic agent. First, we compared the pharmacokinetic profiles of ripasudil in humans and rats. The results indicated rapid disappearance of ripasudil from the circulation after instillation in humans and its level remained relatively high only in M1. In contrast, we found six metabolites from M1 to M6 in plasma after oral administration to rats. 4. Analysis of enzyme kinetics using S9 showed that the formation of M1 is the major metabolic pathway of ripasudil in humans even though CYP3A4/3A5 and CYP2C8/3A4/3A5 were associated with the formation of M2 and M4, respectively. In conclusion, AO causes differences in ripasudil metabolism between species. PMID- 26678039 TI - Readability of Invasive Procedure Consent Forms. AB - BACKGROUND: Informed consent is a pillar of ethical medicine which requires patients to fully comprehend relevant issues including the risks, benefits, and alternatives of an intervention. Given the average reading skill of US adults is at the 8th grade level, the American Medical Association (AMA) and the National Institutes of Health (NIH) recommend patient information materials should not exceed a 6th grade reading level. We hypothesized that text provided in invasive procedure consent forms would exceed recommended readability guidelines for medical information. MATERIALS AND METHODS: To test this hypothesis, we gathered procedure consent forms from all surgical inpatient hospitals in the state of Rhode Island. For each consent form, readability analysis was measured with the following measures: Flesch Reading Ease Formula, Flesch-Kincaid Grade Level, Fog Scale, SMOG Index, Coleman-Liau Index, Automated Readability Index, and Linsear Write Formula. These readability scores were used to calculate a composite Text Readability Consensus Grade Level. RESULTS: Invasive procedure consent forms were found to be written at an average of 15th grade level (i.e., third year of college), which is significantly higher than the average US adult reading level of 8th grade (p < 0.0001) and the AMA/NIH recommended readability guidelines for patient materials of 6th grade (p < 0.0001). CONCLUSION: Invasive procedure consent forms have readability levels which makes comprehension difficult or impossible for many patients. Efforts to improve the readability of procedural consent forms should improve patient understanding regarding their healthcare decisions. PMID- 26678040 TI - WITHDRAWN: Common antiepileptic drugs in pregnancy in women with epilepsy. PMID- 26678041 TI - WITHDRAWN: Psychosocial interventions for the management of chronic orofacial pain. PMID- 26678042 TI - Updating the proteome of the uncultivable hemotrophic Mycoplasma suis in experimentally infected pigs. AB - Mycoplasma suis belongs to the hemotrophic mycoplasmas that are associated with acute and chronic anemia in a wide range of livestock and wild animals. The inability to culture M. suis in vitro has hindered its characterization at the molecular level. Since the publication of M. suis genome sequences in 2011 only one proteome study has been published. Aim of the presented study was to significantly extend the proteome coverage of M. suis strain KI_3806 during acute infection by applying three different protein extraction methods followed by 1D SDS-PAGE and LC-MS/MS. A total of 404 of 795 M. suis KI_3806 proteins (50.8%) were identified. Data analysis revealed the expression of 83.7% of the predicted ORFs with assigned functions but also highlights the expression of 179 of 523 (34.2%) hypothetical proteins with unknown functions. Computational analyses identified expressed membrane-associated hypothetical proteins that might be involved in adhesion or host-pathogen interaction. Furthermore, analyses of the expressed proteins indicated the existence of a hexose-6-phosphate-transporter and an ECF transporter. In conclusion, our proteome study provides a further step toward the elucidation of the unique life cycle of M. suis and the establishment of an in vitro culture. All MS data have been deposited in the ProteomeXchange with identifier PXD002294 (http://proteomecentral.proteomexchange.org/dataset/PXD002294). PMID- 26678043 TI - Does sperm DNA fragmentation affect the developmental potential and the incidence of apoptosis following blastomere biopsy? AB - Common methods employed in assisted reproduction technology (ART) include intracytoplasmic sperm injection (ICSI) with an unspecified level of sperm DNA fragmentation (SDF) and preimplantation genetic diagnosis (PGD). The aim of this study was to investigate the impact of SDF on human preimplantation embryo development and the incidence of apoptosis following a single blastomere biopsy. Using sperm chromatin dispersion (SCD) to assess SDF, a total of 20 processed semen samples were categorized into two groups; group I: SDF <=30% and group II: SDF >30%. After ICSI, fertilization, cleavage, and embryo quality score were assessed. A single blastomere was biopsied from day 3 embryos and development was monitored on day 4. The frequency of apoptosis in biopsied embryos was assayed by TUNEL and the level of BCL-2, BAX, hsa-mir-15a, and hsa-mir-16-1 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). SCD was found to be negatively correlated with sperm motility and normal form spermatozoa (p < 0.05). The rate of fertilization, cleavage, and embryo quality score were not significantly different between the two groups (all p > 0.05). SDF >30% had no negative effect on potential development and did not increase the proportion of apoptotic cells and the level of apoptosis-related genes and microRNAs (miRNAs) in group II vs. group I (p > 0.05). It appears that at the levels assessed paternal genome damage had little if any negative effect on preimplantaton embryo development and apoptosis following single blastomere biopsy. This may reflect the selection of morphologically normal sperm for ICSI and the repair capacity of the oocyte. PMID- 26678044 TI - Effect of inbreeding depression on bull sperm quality and field fertility. AB - The present study investigated the effect of inbreeding depression on sperm quality using automated and objective methods and subsequent effects on beef bull field fertility. Individual inbreeding coefficient (F) values and field fertility data were determined using a dataset of AI bulls belonging to the Spanish Retinta Breeders Association (Asociacion Nacional de Criadores de Ganado Vacuno Selecto de Raza Retinta (ANCRE)). Animals were clustered in two groups according to the F values as follows: (1) a high inbreeding group (HI; F>=13.5%, mean 16.3); and (2) a non-inbreeding group (NI; F=0%). In total, 17 different assessments were performed in both experimental groups, including evaluation of sperm morphology, acrosomal and DNA status, sperm plasma membrane integrity and function (hypo osmotic swelling test), 10 kinetic parameters and the structure of sperm subpopulations. Sperm morphology, acrosomal and DNA status and osmotic tolerance were similar in both groups. Three velocity parameters (curvilinear velocity, straight line velocity and average path velocity) and the amplitude of lateral head displacement were higher in HI (P<0.05). Cluster analysis of kinematic parameters revealed three different sperm subpopulations (sP1, sP2 and sP3), with the proportion of the sP1 population (highly active but non-progressive spermatozoa) being significantly (P<0.05) higher in the HI group. Field fertility was assessed using two calving record datasets. In a smaller database including only bulls evaluated in the present study, there was a significant increase in the calving interval of cows sired with HI bulls. Conversely, in an extended genetic analysis of the ANCRE database, inbreeding only explained a small part of the variation in calving interval, and the results of regression analysis were not significant among bulls. The findings of the present study suggest that high inbreeding levels have a moderate effect on bull semen quality, with an increased percentage of highly active but non-progressive spermatozoa, but only when F values reached a certain threshold. This motility pattern could explain, in part, the higher calving interval produced by inbred bulls under field conditions. PMID- 26678045 TI - Correction: Differential Effects of Conservational Management on SOC Accumulation in the Grasslands of China. PMID- 26678046 TI - Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin/Proteasome Degradation. AB - Protein phosphatase 2A (PP2A) is a conserved essential enzyme that is implicated as a tumor suppressor based on its central role in phosphorylation-dependent signaling pathways. Protein phosphatase methyl esterase (PME-1) catalyzes specifically the demethylation of the C-terminal Leu309 residue of PP2A catalytic subunit (PP2Ac). It has been shown that PME-1 affects the activity of PP2A by demethylating PP2Ac, but also by directly binding to the phosphatase active site, suggesting loss of PME-1 in cells would enhance PP2A activity. However, here we show that PME-1 knockout mouse embryonic fibroblasts (MEFs) exhibit lower PP2A activity than wild type MEFs. Loss of PME-1 enhanced poly-ubiquitination of PP2Ac and shortened the half-life of PP2Ac protein resulting in reduced PP2Ac levels. Chemical inhibition of PME-1 and rescue experiments with wild type and mutated PME-1 revealed methyl-esterase activity was necessary to maintain PP2Ac protein levels. Our data demonstrate that PME-1 methyl-esterase activity protects PP2Ac from ubiquitin/proteasome degradation. PMID- 26678047 TI - Risk Factors for Maternal Mortality in Rural Tigray, Northern Ethiopia: A Case Control Study. AB - BACKGROUND: Maternal mortality continues to have devastating impacts in many societies, where it constitutes a leading cause of death, and thus remains a core issue in international development. Nevertheless, individual determinants of maternal mortality are often unclear and subject to local variation. This study aims to characterise individual risk factors for maternal mortality in Tigray, Ethiopia. METHODS: A community-based case-control study was conducted, with 62 cases and 248 controls from six randomly-selected rural districts. All maternal deaths between May 2012 and September 2013 were recruited as cases and a random sample of mothers who delivered in the same communities within the same time period were taken as controls. Multiple logistic regression was used to identify independent determinants of maternal mortality. RESULTS: Four independent individual risk factors, significantly associated with maternal death, emerged. Women who were not members of the voluntary Women's Development Army were more likely to experience maternal death (OR 2.07, 95% CI 1.04-4.11), as were women whose husbands or partners had below-median scores for involvement during pregnancy (OR 2.19, 95% CI 1.14-4.18). Women with a pre-existing history of other illness were also at increased risk (OR 5.58, 95% CI 2.17-14.30), as were those who had never used contraceptives (OR 2.58, 95% CI 1.37-4.85). Previous pregnancy complications, a below-median number of antenatal care visits and a woman's lack of involvement in health care decision making were significant bivariable risks that were not significant in the multivariable model. CONCLUSIONS: The findings suggest that interventions aimed at reducing maternal mortality need to focus on encouraging membership of the Women's Development Army, enhancing husbands' involvement in maternal health services, improving linkages between maternity care and other disease-specific programmes and ensuring that women with previous illnesses or non-users of contraceptive services are identified and followed-up as being at increased risk during pregnancy and childbirth. PMID- 26678049 TI - The Power of Two: Epigenetics and Twins. PMID- 26678048 TI - The Inflammatory Transcription Factors NFkappaB, STAT1 and STAT3 Drive Age Associated Transcriptional Changes in the Human Kidney. AB - Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFkappaB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNgamma (a STAT1 activator), or TNFalpha (an NFkappaB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFkappaB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFkappaB contributes to renal aging phenotypes. Our results suggest that NFkappaB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID- 26678050 TI - Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass. AB - The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs. PMID- 26678051 TI - Epigenome-Wide DNA Methylation Analysis of Monozygotic Twins Discordant for Diurnal Preference. AB - Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins' buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding. PMID- 26678052 TI - Sharing a Placenta is Associated With a Greater Similarity in DNA Methylation in Monochorionic Versus Dichorionic Twin Pars in Blood at Age 14. AB - Monozygotic (MZ) twins provide a natural system for investigating developmental plasticity and the potential epigenetic origins of disease. A major difference in the intrauterine environment between MZ pairs is whether they share a common placenta or have separate placentas. Using DNA methylation measured at >400,000 points in the genome on the Illumina HumanMethylation450 array, we demonstrate that the co-twins of MZ pairs (average age of 14) that shared a common placenta (n = 18 pairs) have more similar DNA methylation levels in blood throughout the genome relative to those with separate placentas (n = 16 pairs). Functional annotation of the genomic regions that show significantly different correlation between monochorionic (MC) and dichorionic (DC) MZ pairs found an over representation of genes involved in the regulation of transcription, neuronal development, and cellular differentiation. These results support the idea that prenatal environmental exposures may have a lasting effect on an individual's epigenetic landscape, and the potential for these changes to have functional consequences. PMID- 26678053 TI - Genetic and Environmental Stability of Neuroticism From Adolescence to Adulthood. AB - Longitudinal studies of neuroticism have shown that, on average, neuroticism scores decrease from adolescence to adulthood. The heritability of neuroticism is estimated between 0.30 and 0.60 and does not seem to vary greatly as a function of age. Shared environmental effects are rarely reported. Less is known about the role of genetic and environmental influences on the rank order stability of neuroticism in the period from adolescence to adulthood. We studied the stability of neuroticism in a cohort sequential (classical) twin design, from adolescence (age 14 years) to young adulthood (age 32 years). A genetic simplex model that was fitted to the longitudinal neuroticism data showed that the genetic stability of neuroticism was relatively high (genetic correlations between adjacent age bins >0.9), and increased from adolescence to adulthood. Environmental stability was appreciably lower (environmental correlations between adjacent age bins were between 0.3 and 0.6). This low stability was largely due to age-specific environmental variance, which was dominated by measurement error. This attenuated the age-to-age environmental correlations. We constructed an environmental covariance matrix corrected for this error, under the strong assumption that all age-specific environmental variance is error variance. The environmental (co)variance matrix corrected for attenuation revealed highly stable environmental influences on neuroticism (correlations between adjacent age bins were between 0.7 and 0.9). Our results indicate that both genetic and environmental influences have enduring effects on individual differences in neuroticism. PMID- 26678054 TI - The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium. AB - Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9 11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases. PMID- 26678055 TI - The Fourth International Network of Twin Registries: Overview from Osaka/Research Reviews: Familial Fraternal Twinning; Twin Study of Masculine Faces; Physical Aggression and Epigenetics; Prenatal Education for Parents of Twins/Current Events: 2016 Guinness Book of World Records; Oldest Living Male Twins; Twins Reunited at Sixty-Nine; Panda Twins; Twins.com. AB - The 4th International Network of Twin Registries (INTR) Consortium Meeting took place in Osaka, Japan, September 28-29, 2015. The venue was the Osaka Medical Center for Medical Innovation and Translational Research. An overview of presentations and other activities is provided. Next, 1930s research on familial fraternal twinning, preference for masculine faces, physical aggression and epigenetics, and a prenatal education program for parents of multiples are described. Current twin-related events include the 2016 Guinness Book of World Records (GWR), the oldest living male twins, newly reunited twins, the birth of panda twins and a controversial twin-based website. PMID- 26678058 TI - The complete mitochondrial genome of Dixella aestivalis (Diptera: Nematocera: Dixidae). AB - Dixidae, meniscus midges, belong to the suborder Nematocera of the order Diptera. The family includes 197 known species classified in nine genera. The complete mitochondrial genome of the Dixella aestivalis (Meigen) from the United Kingdom is reported here, along with its annotation and comparison with the genome of an unidentified species of Dixella from China. The circular genome consists of 16 465 bp and has a gene content consisting of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a non-coding, A + T-rich, control region. The mitochondrial genome of D. aestivalis can be used to identify genetic markers for species identification, and will be valuable for resolving phylogenetic relationships within the genus, family Dixidae and suborder Nematocera. PMID- 26678059 TI - Pre- and postloss features of adolescent suicide bereavement: A systematic review. AB - Despite increasing clinical and research interest in suicide bereavement the impact of suicide on adolescents is still poorly understood. This systematic review aims to disentangle pre- and postloss features that affect response to grief in this age group. The literature was analyzed after a systematic search and hand-check of retrieved articles. The impact of suicide is affected by (a) preloss features related to personal/family history of mental health, family life, suicidal behavior, and type and emotional closeness of relationship; and (b) postloss issues such as quality of remaining relationships. Future research and bereavement support should consider these broader contexts. PMID- 26678060 TI - IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis. AB - BACKGROUND: Psoriasis is characterized by multiple genetic variations. Some of these variations, such as the presence of HLA-Cw6 or TNFAIP3 single-nucleotide polymorphisms (SNPs), have been correlated to the response to biologic treatments. OBJECTIVE: The aim of our study was to evaluate the effects of IL12B and IL6 SNPs on the response to ustekinumab. METHODS: We retrospectively analyzed the genotypes of 64 patients who had been treated with ustekinumab for up to 1 year. Efficacy data were evaluated using 'intention to treat-last observation carried forward' analysis. RESULTS: We confirmed the positive role of HLA-Cw6 as a predictor of the response to ustekinumab and discovered that presence of the GG genotype on the IL12B rs6887695 SNP and absence of the AA genotype on the IL12B rs3212227 SNP significantly increase the probability of therapeutic success in HLA-Cw6 positive patients. CONCLUSIONS: The availability of pharmacogenetic data will influence therapeutic decisions in the clinical management of psoriatic patients. PMID- 26678061 TI - Reactive Balance Control in Response to Perturbation in Unilateral Stance: Interaction Effects of Direction, Displacement and Velocity on Compensatory Neuromuscular and Kinematic Responses. AB - Unexpected sudden perturbations challenge postural equilibrium and require reactive compensation. This study aimed to assess interaction effects of the direction, displacement and velocity of perturbations on electromyographic (EMG) activity, centre of pressure (COP) displacement and joint kinematics to detect neuromuscular characteristics (phasic and segmental) and kinematic strategies of compensatory reactions in an unilateral balance paradigm. In 20 subjects, COP displacement and velocity, ankle, knee and hip joint excursions and EMG during short (SLR), medium (MLR) and long latency response (LLR) of four shank and five thigh muscles were analysed during random surface translations varying in direction (anterior-posterior (sagittal plane), medial-lateral (frontal plane)), displacement (2 vs. 3 cm) and velocity (0.11 vs. 0.18 m/s) of perturbation when balancing on one leg on a movable platform. Phases: SLR and MLR were scaled to increased velocity (P<0.05); LLR was scaled to increased displacement (P<0.05). Segments: phasic interrelationships were accompanied by segmental distinctions: distal muscles were used for fast compensation in SLR (P<0.05) and proximal muscles to stabilise in LLR (P<0.05). Kinematics: ankle joints compensated for both increasing displacement and velocity in all directions (P<0.05), whereas knee joint deflections were particularly sensitive to increasing displacement in the sagittal (P<0.05) and hip joint deflections to increasing velocity in the frontal plane (P<0.05). COP measures increased with increasing perturbation velocity and displacement (P<0.05). Interaction effects indicate that compensatory responses are based on complex processes, including different postural strategies characterised by phasic and segmental specifications, precisely adjusted to the type of balance disturbance. To regain balance after surface translation, muscles of the distal segment govern the quick regain of equilibrium; the muscles of the proximal limb serve as delayed stabilisers after a balance disturbance. Further, a kinematic distinction regarding the compensation for balance disturbance indicated different plane- and segment specific sensitivities with respect to the determinants displacement and velocity. PMID- 26678063 TI - The impact of community-based eHealth self-management intervention among elderly living alone with hypertension. AB - Introduction This study intended to examine the effect of an eHealth self management (eHSM) intervention on elderly Korean persons who live alone in a community. Methods A quasi-experimental study was designed, and a total of 64 elderly persons (intervention n = 31, control n = 33) with hypertension (a systolic blood pressure measurement of >=140 and/or a diastolic blood pressure >=90 mm Hg) or taking anti-hypertensive medication participated. The eHSM intervention consisted of a four-week, in-class educational phase, community based eHealth monitoring, and monthly telephone counselling for 24 weeks. Results The primary outcome measurement of the study was BP, and secondary outcomes included psycho-behavioural variables. Specifically, the systolic BP among intervention group participants was 133.9 mm Hg at baseline and 122.5 mm Hg after 24 weeks of follow-up. Participants in the intervention group showed greater improvement in self-efficacy, self-care behaviour, and social support than did participants in the control group 24 weeks post-intervention. Discussion The results highlight the clinical efficacy of an eHSM intervention composed of a four-week education program, self-monitoring, and follow-up counselling. The eHSM intervention should be expanded to include community-dwelling elderly persons with hypertension to improve the self-management of hypertension and control of blood pressure. PMID- 26678062 TI - Toll-like receptors, triggering receptor expressed on myeloid cells family members and receptor for advanced glycation end-products in allergic airway inflammation. AB - Asthma is a chronic disorder of the airways characterized by cellular infiltration, airway hyper-responsive and airway inflammation. Innate immune cells are the first line of defense against endogenous and exogenous signals in the airways and as such possess a diverse array of pattern recognition receptors. Toll-like receptors are crucial sentinels which when activated, can either promote or ameliorate the inflammatory response in predisposed individuals. The recently discovered triggering receptor expressed on myeloid cells family members are emerging mediators of inflammation. These receptors are believed to modulate inflammatory responses by collaborating with classic PRRs. Endogenous signals like HMGB-1, signaling through the receptor for advanced glycation end products, also promotes inflammation, however, its contribution to inflammation in the airways is not well known. Here, we discuss the role of each receptor in airway inflammation and highlight potential synergistic mechanisms, which contribute to disease pathogenesis in allergic asthma. PMID- 26678066 TI - Switching off pain at the source: is this the end for opioid pain relief? AB - Opiates, like morphine or codeine, are used to suppress nociceptive pain in humans. While these drugs can provide effective pain relief, they also cause an extensive array of undesirable side effects, including central depression, sedation and addiction. Relatively recently, the sodium channel Nav1.7 was shown to be essential for pain perception in humans. Based on this, we describe a new technical approach that may be useful for the prolonged suppression of nociceptive pain. The technique uses a harmless adeno-associated virus carrying a short hairpin RNA to silence Nav1.7 ion channels only in sensory neurons underlying pain perception. The major advantage is that pain may be suppressed at the source for many months, without the side effects of opiates. PMID- 26678064 TI - A novel analysis strategy for integrating methylation and expression data reveals core pathways for thyroid cancer aetiology. AB - BACKGROUND: Recently, a wide range of diseases have been associated with changes in DNA methylation levels, which play a vital role in gene expression regulation. With ongoing developments in technology, attempts to understand disease mechanism have benefited greatly from epigenetics and transcriptomics studies. In this work, we have used expression and methylation data of thyroid carcinoma as a case study and explored how to optimally incorporate expression and methylation information into the disease study when both data are available. Moreover, we have also investigated whether there are important post-translational modifiers which could drive critical insights on thyroid cancer genetics. RESULTS: In this study, we have conducted a threshold analysis for varying methylation levels to identify whether setting a methylation level threshold increases the performance of functional enrichment. Moreover, in order to decide on best-performing analysis strategy, we have performed data integration analysis including comparison of 10 different analysis strategies. As a result, combining methylation with expression and using genes with more than 15% methylation change led to optimal detection rate of thyroid-cancer associated pathways in top 20 functional enrichment results. Furthermore, pooling the data from different experiments increased analysis confidence by improving the data range. Consequently, we have identified 207 transcription factors and 245 post translational modifiers with more than 15% methylation change which may be important in understanding underlying mechanisms of thyroid cancer. CONCLUSION: While only expression or only methylation information would not reveal both primary and secondary mechanisms involved in disease state, combining expression and methylation led to a better detection of thyroid cancer-related genes and pathways that are found in the recent literature. Moreover, focusing on genes that have certain level of methylation change improved the functional enrichment results, revealing the core pathways involved in disease development such as; endocytosis, apoptosis, glutamatergic synapse, MAPK, ErbB, TGF-beta and Toll-like receptor pathways. Overall, in addition to novel analysis framework, our study reveals important thyroid-cancer related mechanisms, secondary molecular alterations and contributes to better knowledge of thyroid cancer aetiology. PMID- 26678067 TI - Associations between neighbourhood characteristics and community mobility in older adults with chronic health conditions. AB - PURPOSE: To explore associations between perceptions of neighbourhood built and social characteristics and satisfaction with community mobility in older adults with chronic health conditions. METHOD: Two hundred and thirty-seven community dwelling adults aged 60 years or more with one or more of arthritis (osteoarthritis or rheumatoid arthritis), chronic obstructive pulmonary disease, diabetes or heart disease completed a cross-sectional, mailed survey. The survey addressed community mobility and 11 neighbourhood characteristics: amenities (three types), problems (six), social cohesion and safety. Analysis involved logistic regression modeling for each neighbourhood characteristic. RESULTS: Satisfaction with community mobility was associated with perception of no traffic problems (OR = 3.0, 95% CI = 1.4-6.2, p <= 0.05) and neighbourhood safety (OR = 3.4, 95% CI = 1.2-9.8, p <= 0.05), adjusted for age, ability to walk several blocks and depressive symptoms. CONCLUSION: Satisfaction with community mobility is associated with neighbourhood safety and no traffic problems among older adults with chronic conditions. While further research is needed to explore these neighbourhood characteristics in more detail and to examine causation, addressing these neighbourhood characteristics in health services or community initiatives may help promote community mobility in this population. Implications for Rehabilitation Community mobility, or the ability to move about one's community, is a key aspect of participation that enables other aspects of community participation. Good community mobility is associated with perception of no traffic problems and neighbourhood safety among older adults. Considering and addressing a broad range of environmental influences has the potential to improve community mobility in older adults, beyond traditional approaches. Health professionals can work with clients to develop strategies to avoid traffic and safety problems and can work with communities to develop safe spaces within neighbourhoods, to improve community mobility in older adults. PMID- 26678068 TI - Development of an observational measure of social disinhibition after traumatic brain injury. AB - INTRODUCTION: This study aimed to validate a new observational measure of socially disinhibited behavior for use in a population of individuals with traumatic brain injury (TBI). METHOD: Participants were twenty-two adults with severe TBI (mean age = 50.45 years) and 21 healthy comparison participants (mean age = 45.29 years). Ratings of observed social disinhibition were correlated with the disinhibition domain scores of the Neuropsychiatric Inventory-Disinhibition (NPI-D) and with Sydney Psychosocial Reintegration Scale (SPRS) scores. A regression analysis was undertaken to determine whether formal measures of disinhibition could predict observed disinhibition. RESULTS: The interrater absolute agreement for the social disinhibition ratings was good, intraclass correlation coefficient (ICC) = .69. Participants with TBI were rated as significantly more disinhibited than comparison participants, t(25.05) = -2.07, p = .049. The ratings were positively correlated with the NPI frequency score (r = .45, p = .038) and distress score (r = .45, p = .035). The ratings were not related to change in employment or in interpersonal relationships on the SPRS, and formal measures of disinhibition were unable to predict observed social disinhibition. CONCLUSIONS: This study demonstrates good interrater reliability and construct validity of the observational measure. The results evidence the usefulness of this measure and the NPI-D for detecting social disinhibition after TBI. PMID- 26678069 TI - Invasive Cancer Incidence and Survival--United States, 2012. AB - Many factors contribute to changes in cancer incidence, including changes in risk exposures or changes in the use of cancer screening tests (1). To monitor changes in cancer incidence and assess progress toward achieving Healthy People 2020 objectives, CDC analyzed data from U.S. Cancer Statistics (USCS) for 2012, the most recent data available. USCS includes high quality incidence data from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, survival data from NPCR, and mortality data from the National Vital Statistics System (2). In 2012, a total of 1,529,078 invasive cancers were reported to cancer registries in the United States (excluding Nevada), for an annual incidence rate of 440 cases per 100,000 persons. Cancer incidence rates were higher among males (483) than females (412), highest among blacks (446), and ranged by state, from 371 to 515 per 100,000 persons (355 in Puerto Rico). The proportion of persons with cancer who survived >=5 years after diagnosis was 66%. The proportion was the same for males and females (66%) but lower among blacks (60%) compared with whites (66%). These cancer incidence, survival, and mortality surveillance data are continually tracked and used by states to effectively plan health care allocation and support services. PMID- 26678070 TI - Who Shot Ya? How Emergency Departments Can Collect Reliable Police Shooting Data. AB - This paper examines an alternative solution for collecting reliable police shooting data. One alternative is the collection of police shooting data from hospital trauma units, specifically hospital-based violence intervention programs. These programs are situated in Level I trauma units in many major cities in USA. While the intent of these programs is to reduce the risk factors associated with trauma recidivism among victims of violent injury, they also collect reliable data on the number of individuals treated for gunshot wounds. While most trauma units do a great job collecting data on mode of injury, many do not collect data on the circumstances surrounding the injury, particularly police involved shootings. Research protocol on firearm-related injury conducted in emergency departments typically does not allow researchers to interview victims of violent injury who are under arrest. Most victims of nonfatal police-involved shootings are under arrest at the time they are treated by the ED for their injury. Research protocol on victims of violent injury often excludes individuals under arrest; they fall under the exclusion criteria when recruiting potential participants for research on violence. Researchers working in hospital emergency departments are prohibited from recruited individuals under arrests. The trauma staff, particularly ED physicians and nurses, are in a strategic position to collect this kind of data. Thus, this paper examines how trauma units can serve as an alternative in the reliable collection of police shooting data. PMID- 26678071 TI - Constructing a Time-Invariant Measure of the Socio-economic Status of U.S. Census Tracts. AB - Contextual research on time and place requires a consistent measurement instrument for neighborhood conditions in order to make unbiased inferences about neighborhood change. We develop such a time-invariant measure of neighborhood socio-economic status (NSES) using exploratory and confirmatory factor analyses fit to census data at the tract level from the 1990 and 2000 U.S. Censuses and the 2008-2012 American Community Survey. A single factor model fit the data well at all three time periods, and factor loadings--but not indicator intercepts- could be constrained to equality over time without decrement to fit. After addressing remaining longitudinal measurement bias, we found that NSES increased from 1990 to 2000, and then--consistent with the timing of the "Great Recession"- declined in 2008-2012 to a level approaching that of 1990. Our approach for evaluating and adjusting for time-invariance is not only instructive for studies of NSES but also more generally for longitudinal studies in which the variable of interest is a latent construct. PMID- 26678072 TI - Demographic Predictors of Event-Level Associations between Alcohol Consumption and Sexual Behavior. AB - Alcohol consumption is associated with sexual behavior and outcomes, though research indicates a variety of moderating factors, including demographic characteristics. To better target interventions aimed at alcohol-related sexual risk behavior, our analyses simultaneously examine demographic predictors of both day- and event-level associations between alcohol consumption and sexual behavior in a sample of young adults (N = 301) who are sexually active and consume alcohol. Young adults (aged 18-29) recruited using time-space sampling and incentivized snowball sampling completed a survey and a timeline follow-back calendar reporting alcohol consumption and sexual behavior in the past 30 days. On a given day, a greater number of drinks consumed was associated with higher likelihood of sex occurring, particularly for women and single participants. During a given sexual event, number of drinks consumed was not associated with condom use, nor did any demographic predictors predict that association. Findings highlight associations between alcohol and sexual behavior, though not between alcohol and sexual risk behavior, highlighting the need for additional research exploring the complex role of alcohol in sexual risk behavior and the need to develop prevention efforts to minimize the role of alcohol in the initiation of sexual encounters. PMID- 26678073 TI - Accurate reconstruction of viral quasispecies spectra through improved estimation of strain richness. AB - BACKGROUND: Estimating the number of different species (richness) in a mixed microbial population has been a main focus in metagenomic research. Existing methods of species richness estimation ride on the assumption that the reads in each assembled contig correspond to only one of the microbial genomes in the population. This assumption and the underlying probabilistic formulations of existing methods are not useful for quasispecies populations where the strains are highly genetically related. RESULTS: On benchmark data sets, our estimation method provided accurate richness estimates (< 0.2 median estimation error) and improved the precision of ViQuaS by 2%-13% and F-score by 1%-9% without compromising the recall rates. We also demonstrate that our estimation method can be used to improve the precision and F-score of ShoRAH by 0%-7% and 0%-5% respectively. CONCLUSIONS: The proposed probabilistic estimation method can be used to estimate the richness of viral populations with a quasispecies behavior and to improve the accuracy of the quasispecies spectra reconstructed by the existing methods ViQuaS and ShoRAH in the presence of a moderate level of technical sequencing errors. AVAILABILITY: http://sourceforge.net/projects/viquas/. PMID- 26678074 TI - The Golgi-Associated Plant Pathogenesis-Related Protein GAPR-1 Enhances Type I Interferon Signaling Pathway in Response to Toll-Like Receptor 4. AB - Lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4) through the TIRAP MyD88 dependent and TRAM-TRIF dependent signaling pathways, respectively. However, the underlying relevance between two signaling pathways remains largely elusive. Here, we investigated the role of the Golgi-Associated plant Pathogenesis-Related protein (GAPR-1) in type I interferon (IFN) signaling pathway in response to TLR4. We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7 mediated disruption of the TRAM-TRIF complex to trigger IFN-beta and the IL10 secretion. Collectively, our study identified a previously unrecognized role for GAPR-1 to control a unifying TLR4 signaling complex and to regulate type I IFN signaling activation. Understanding the mechanism of GAPR-1 in type I IFN signaling pathway would provide strategies for treatment of infectious diseases. PMID- 26678075 TI - Serum Sialyl-Tn (STN) as a Tumor Marker in Patients with Endometrial Cancer. AB - There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60 years (28-83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44 months (1-83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p = 0.02) and lymph node metastasis (p = 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer. PMID- 26678076 TI - miRNA Isolation from FFPET Specimen: A Technical Comparison of miRNA and Total RNA Isolation Methods. AB - MiRNA remain stable for detection and PCR-based amplification in FFPE tissue samples. Several miRNA extraction kits are available, however miRNA fraction, as part of total RNA can be isolated using total RNA purification methods, as well. Our primary aim was to compare four different miRNA and total RNA isolation methods from FFPE tissues. Further purposes were to evaluate quantitatively and qualitatively the yield of the isolated miRNA. MiRNAs were isolated from normal colorectal cancer FFPE specimens from the same patients. Two miRNA isolation kits (High Pure miRNA Isolation Kit, miRCURYTM RNA Isolation Kit) and two total RNA isolation kits were compared (High Pure RNA Paraffin Kit, MagNA Pure 96 Cellular RNA LV Kit). Quantity and quality were determined, expression analysis was performed by real-time PCR using qPCR Human Panel I + II (Exiqon) method detecting 742 human miRNAs in parallel. The yield of total RNA was found to be higher than miRNA purification protocols (in CRC: Ex: 0203 +/- 0021 MUg; HPm: 1,45 +/- 0,8 MUg; HPp: 21,36 +/- 4,98 MUg; MP: 8,6 +/- 5,1 MUg). MiRNAs were detected in lower relative quantity of total RNA compared to the miRNA kits. Higher number of miRNAs could be detected by the miRNA isolation kits in comparison to the total RNA isolation methods. (Ex: 497 +/- 16; HPm: 542 +/- 11; HPp: 332 +/- 36; MP: 295 +/- 74). Colon specific miRNAs (miR-21-5p;-34-5p) give satisfying results by miRNA isolation kits. Although miRNA can be detected also after total RNA isolation methods, for reliable and reproducible miRNA expression profiling the use of miRNA isolation kits are more suitable. PMID- 26678077 TI - Chronic Spontaneous Urticaria: A Questionnaire Survey. AB - BACKGROUND: Chronic spontaneous urticaria (CSU) is urticaria persisting for more than 6 weeks with no identifiable provoking cause and associated with significant disability. OBJECTIVES: The aim of this study was to survey patients with CSU with a view to establishing prognosis, efficacy of treatments, suspected causality, and effects on lifestyle. METHODS: One hundred seventy-four patients with CSU were seen between 2003 and 2013. A questionnaire was sent to all, and 101 participated. RESULTS: The ratio of female to male participants was 4:1. The mean age of onset was 36 years. The average duration of symptoms was 8.8 years, with a range of 0.33 to 55 years. Seven percent of participants had autoimmune thyroiditis, and another 17% had various other autoimmune diseases. Common symptoms were pruritus, disturbed sleep, and anxiety. Slightly more than 70% had missed work or school. Most were frustrated at the lack of efficacy of treatments. CONCLUSIONS: CSU is frequently associated with a history of autoimmune diseases. It may persist for decades and causes significant disruption to lifestyle. PMID- 26678078 TI - Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis. AB - Early and accurate diagnosis of invasive aspergillosis (IA) is one of the most critical steps needed to efficiently treat the infection and reduce the high mortality rates that can occur. We have previously found that the Aspergillus spp. secondary metabolite, bis(methylthio)gliotoxin (bmGT), can be detected in the serum from patients with possible/probable IA. Thus, it could be used as a diagnosis marker of the infection. However, there is no data available concerning the sensitivity, specificity and performance of bmGT to detect the infection. Here, we have performed a prospective study comparing bmGT detection with galactomannan (GM), the most frequently used and adopted approach for IA diagnosis, in 357 sera from 90 episodes of patients at risk of IA. Our results, involving 79 patients that finally met inclusion criteria, suggest that bmGT presents higher sensitivity and positive predictive value (PPV) than GM and similar specificity and negative predictive value (NPV). Importantly, the combination of GM and bmGT increased the PPV (100 %) and NPV (97.5 %) of the individual biomarkers, demonstrating its potential utility in empirical antifungal treatment guidance and withdrawal. These results indicate that bmGT could be a good biomarker candidate for IA diagnosis and, in combination with GM, could result in highly specific diagnosis of IA and management of patients at risk of infection. PMID- 26678079 TI - Replacing a piece of loop-structure in the substrate-binding groove of Aspergillus usamii beta-mannanase, AuMan5A, to improve its enzymatic properties by rational design. AB - To perfect the enzymatic properties of AuMan5A, a mesophilic glycoside hydrolase (GH) family 5 beta-mannanase from Aspergillus usamii, its loop-structure substitution was carried out by rational design and followed by megaprimer PCR. Based on the structural analysis and enzymatic property comparison of various beta-mannanases, a piece of loop-structure with seven amino acids between two beta-strands (betaD and betaE) in the substrate-binding groove, named "Loop DE," was speculated to be correlative to the thermostability and catalytic efficiency of GH family 5 beta-mannanases. Therefore, three AuMan5A's mutants, AuMan5A-Af, AuMan5A-An, and AuMan5A-Th, were designed by substituting a Loop DE sequence ((316)KSPDGGN(322)) of AuMan5A with the corresponding sequences of other three family 5 beta-mannanases, respectively. Then, the mutant-encoding genes, Auman5A Af, Auman5A-An, and Auman5A-Th, were constructed as designed theoretically and then expressed in Pichia pastoris GS115. The expressed recombinant AuMan5A-Af (re AuMan5A-Af) displayed the temperature optimum (T opt) of 75 degrees C, T m value of 76.6 degrees C and half-life (t 1/2) of 480 min at 70 degrees C, which were 10 and 12.1 degrees C higher and 48-fold longer than those of re-AuMan5A, respectively. Its catalytic efficiency (k cat/K m) was 12.7-fold that of re AuMan5A. What is more, the site-directed mutagenesis of D320G in AuMan5A-Af was performed. The T opt and t 1/2 of expressed re-AuMan5A-Af(D320G) decreased to 70 degrees C and 40 min, respectively, while its k cat/K m was only 35 % of that of re-AuMan5A-Af. These results demonstrated that the mutation of G320 (in AuMan5A) into D320 (in AuMan5A-Af) through Loop DE substitution was mainly responsible for the thermostability and catalytic efficiency improvement of AuMan5A-Af. PMID- 26678080 TI - Non-sustained wide complex tachycardia: an underappreciated sign to aid in diagnosis. AB - AIMS: The electrocardiographic (ECG) signs used to differentiate ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrancy are specific but not highly sensitive. The purpose of this study was to define the utility of an underappreciated form of atrioventricular (AV) dissociation at the onset of tachycardia, a single dissociated P wave, in the differentiation of non sustained monomorphic wide complex tachycardia (WCT) in hospitalized patients. METHODS AND RESULTS: We prospectively analysed tracings from 102 consecutive hospitalized patients who had an episode of non-sustained (>=5 beats, <30 s), monomorphic, WCT (>=100 b.p.m.) on telemetry. WCT was classified as VT, SVT with aberrancy, or undifferentiated WCT based on predefined criteria. Of 102 patients with WCT, 3 (3%) had SVT with aberrancy, 43 (42%) had an undifferentiated WCT, and 56 (55%) had VT. ECG evidence of a single dissociated P wave at the onset of tachycardia (i.e. AV dissociation at the onset) was identified in 29 patients (28%) compared with less frequent traditional signs of VT including second-degree ventriculoatrial (VA) block in 18 patients (18%), AV dissociation during tachycardia in 17 patients (17%), fusion beats in 10 patients (10%), and capture beats in 3 patients (3%). On multivariate analysis, only the prematurity index predicted the occurrence of AV dissociation at the onset of the tachycardia (odds ratio 1.239, 95% confidence interval 1.033-1.486, P = 0.021). CONCLUSION: When evaluating WCT in hospitalized patients, a single dissociated P wave at the onset of tachycardia is an easily recognizable diagnostic sign of VT, and is observed more frequently than the other accepted criteria for VT. PMID- 26678081 TI - Evidence for alterations of cortical folding in anorexia nervosa. AB - Anorexia nervosa (AN) is highly heritable, and the perspective on the etiology of AN has changed from a behavioral to a neurobiological and neurodevelopmental view. However, cortical folding as an important marker for deviations in brain development has yet rarely been explored in AN. Hence, in order to determine potential cortical folding alterations, we investigated fine-grained cortical folding in a cohort of 26 patients with AN, of whom 6 patients were recovered regarding their weight at the time point of MRI measurement. MRI-derived cortical folding was computed and compared between patients and healthy controls at about 150,000 points per hemisphere using a surface-based technique (FreeSurfer). Patients with AN exhibited highly significant increased cortical folding in a right dorsolateral prefrontal cortex region (DLPFC). Furthermore, a statistical trend in the same direction was found in the right visual cortex. We did not find a correlation of local cortical folding and current symptoms of the disease. In conclusion, our analyses provide first evidence that altered DLPFC cortical folding plays a role in the etiology of AN. The absence of correlations with clinical parameters implicates a relatively independence of cortical folding alterations from the current symptomatology and might thus be regarded as a trait characteristic of the disease potentially related to other neurobiological features of AN. PMID- 26678082 TI - MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems. AB - Programmable nucleases enable engineering of the genome by utilizing endogenous DNA double-strand break (DSB) repair pathways. Although homologous recombination (HR)-mediated gene knock-in is well established, it cannot necessarily be applied in every cell type and organism because of variable HR frequencies. We recently reported an alternative method of gene knock-in, named the PITCh (Precise Integration into Target Chromosome) system, assisted by microhomology-mediated end-joining (MMEJ). MMEJ harnesses independent machinery from HR, and it requires an extremely short homologous sequence (5-25 bp) for DSB repair, resulting in precise gene knock-in with a more easily constructed donor vector. Here we describe a streamlined protocol for PITCh knock-in, including the design and construction of the PITCh vectors, and their delivery to either human cell lines by transfection or to frog embryos by microinjection. The construction of the PITCh vectors requires only a few days, and the entire process takes ~ 1.5 months to establish knocked-in cells or ~ 1 week from injection to early genotyping in frog embryos. PMID- 26678083 TI - Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. AB - Circulating tumor cells (CTCs) are rare cancer cells that are shed from primary or metastatic tumors into the peripheral blood circulation. Phenotypic and genetic characterization of these rare cells can provide important information to guide cancer staging and treatment, and thus further research into their characteristics and properties is an area of considerable interest. In this protocol, we describe detailed procedures for the production and use of a label free spiral microfluidic device to allow size-based isolation of viable CTCs using hydrodynamic forces that are present in curvilinear microchannels. This spiral system enables us to achieve >= 85% recovery of spiked cells across multiple cancer cell lines and 99.99% depletion of white blood cells in whole blood. The described spiral microfluidic devices can be produced at an extremely low cost using standard microfabrication and soft lithography techniques (2-3 d), and they can be operated using two syringe pumps for lysed blood samples (7.5 ml in 12.5 min for a three-layered multiplexed chip). The fast processing time and the ability to collect CTCs from a large patient blood volume allows this technique to be used experimentally in a broad range of potential genomic and transcriptomic applications. PMID- 26678084 TI - Scalable synthesis and post-modification of a mesoporous metal-organic framework called NU-1000. AB - The synthesis of NU-1000, a highly robust mesoporous (containing pores >2 nm) metal-organic framework (MOF), can be conducted efficiently on a multigram scale from inexpensive starting materials. Tetrabromopyrene and (4 (ethoxycarbonyl)phenyl)boronic acid can easily be coupled to prepare the requisite organic strut with four metal-binding sites in the form of four carboxylic acids, while zirconyl chloride octahydrate is used as a precursor for the well-defined metal oxide clusters. NU-1000 has been reported as an excellent candidate for the separation of gases, and it is a versatile scaffold for heterogeneous catalysis. In particular, it is ideal for the catalytic deactivation of nerve agents, and it shows great promise as a new generic platform for a wide range of applications. Multiple post-synthetic modification protocols have been developed using NU-1000 as the parent material, making it a potentially useful scaffold for several catalytic applications. The procedure for the preparation of NU-1000 can be scaled up reliably, and it is suitable for the production of 50 g of the tetracarboxylic acid containing organic linker and 200 mg-2.5 g of NU-1000. The entire synthesis is performed without purification by column chromatography and can be completed within 10 d. PMID- 26678085 TI - Assessing Pictograph Recognition: A Comparison of Crowdsourcing and Traditional Survey Approaches. AB - BACKGROUND: Compared to traditional methods of participant recruitment, online crowdsourcing platforms provide a fast and low-cost alternative. Amazon Mechanical Turk (MTurk) is a large and well-known crowdsourcing service. It has developed into the leading platform for crowdsourcing recruitment. OBJECTIVE: To explore the application of online crowdsourcing for health informatics research, specifically the testing of medical pictographs. METHODS: A set of pictographs created for cardiovascular hospital discharge instructions was tested for recognition. This set of illustrations (n=486) was first tested through an in person survey in a hospital setting (n=150) and then using online MTurk participants (n=150). We analyzed these survey results to determine their comparability. RESULTS: Both the demographics and the pictograph recognition rates of online participants were different from those of the in-person participants. In the multivariable linear regression model comparing the 2 groups, the MTurk group scored significantly higher than the hospital sample after adjusting for potential demographic characteristics (adjusted mean difference 0.18, 95% CI 0.08-0.28, P<.001). The adjusted mean ratings were 2.95 (95% CI 2.89-3.02) for the in-person hospital sample and 3.14 (95% CI 3.07-3.20) for the online MTurk sample on a 4-point Likert scale (1=totally incorrect, 4=totally correct). CONCLUSIONS: The findings suggest that crowdsourcing is a viable complement to traditional in-person surveys, but it cannot replace them. PMID- 26678086 TI - Clinicopathological and prognostic significance of chemokine receptor CXCR4 in patients with bone and soft tissue sarcoma: a meta-analysis. AB - The prognostic significance of CXC chemokine receptor 4 (CXCR4) in patients with bone and soft tissue sarcomas remains controversial. To investigate the impact of its expression on survival and clinicopathological features, we performed a meta analysis. Comprehensive literature searches were conducted in PubMed, Web of Science, Embase and Cochrane Library for relevant studies. In total, 12 studies with 997 sarcoma patients were included. CXCR4 expression was found to be significantly associated with poor overall survival (HR 2.37, 95 % CI 1.86-3.01; P < 0.001). Further, when the analysis was stratified by histological subtypes (bony sarcoma including osteosarcoma and Ewing sarcoma and soft tissue sarcoma including synovial sarcoma and rhabdomyosarcoma), statistical analysis method (multivariate analysis and univariate analysis) and CXCR4 measuring method (IHC or RT-PCR), the significant correlation to poor overall survival was also observed except for that in Ewing sarcoma and RT-PCR groups. As for clinicopathological features, CXCR4 expression was significantly associated with higher rate of metastasis (OR 6.97, 95 % CI 2.28-21.31; P = 0.001) and higher tumor stage (OR 7.55, 95 % CI 1.25-45.47; P = 0.027), but not associated with gender, age and tumor site. In conclusion, CXCR4 expression may be an effective predictive factor of poor prognosis and clinicopathological features for bone and soft tissue sarcomas. Further studies are needed to validate our findings. PMID- 26678087 TI - Zinc enhancement of cytidine deaminase activity highlights a potential allosteric role of loop-3 in regulating APOBEC3 enzymes. AB - The strong association of APOBEC3 cytidine deaminases with somatic mutations leading to cancers accentuates the importance of their tight intracellular regulation to minimize cellular transformations. We reveal a novel allosteric regulatory mechanism of APOBEC3 enzymes showing that APOBEC3G and APOBEC3A coordination of a secondary zinc ion, reminiscent to ancestral deoxycytidylate deaminases, enhances deamination activity. Zinc binding is pinpointed to loop-3 which whilst highly variable harbors a catalytically essential and spatially conserved asparagine at its N-terminus. We suggest that loop-3 may play a general role in allosterically tuning the activity of zinc-dependent cytidine deaminase family members. PMID- 26678088 TI - Long-term Expectations of Vagus Nerve Stimulation: A Look at Battery Replacement and Revision Surgery. AB - BACKGROUND: Vagus nerve stimulation (VNS) is an established surgical treatment for medically intractable epilepsy with more than 75 000 devices implanted worldwide. While there are many reports documenting efficacy, complications, and clinical use, there are very few reports concerning VNS battery replacement and revision surgeries. OBJECTIVE: To review our experience with VNS battery replacement and revision surgery. METHODS: We retrospectively reviewed 1144 consecutive VNS procedures performed by a single surgeon between 1998 and 2012. Six hundred forty-four of those procedures were the initial placement of the VNS device. These patients were then followed to determine when a battery change occurred and what type of revision or removal was necessary. RESULTS: In the study, 46% of patients required at least 1 or more type of battery replacement or revision surgery. The most common types of surgery were for generator battery depletion (27%), poor efficacy (9%), and lead malfunction (8%). Only 2% of patients were noted to have an infection. CONCLUSION: VNS battery replacement, revisions, and removals account for almost one-half of all VNS procedures. Our findings suggest important long-term expectations for VNS including expected complications, battery life, and other surgical issues. Review of the literature suggests that this is the first large review of VNS revisions by a single center. Our findings are important to better characterize long-term surgical expectations of VNS therapy. A significant portion of patients undergoing VNS therapy will eventually require revision. PMID- 26678091 TI - Owning the body in the mirror: The effect of visual perspective and mirror view on the full-body illusion. AB - Mirrors allow us to view our own body from a third-person (observer) perspective. However, how viewing ourselves through a mirror affects central body representations compared with true third-person perspective is not fully understood. Across a series of experiments, multisensory full-body illusions were used to modulate feelings of ownership over a mannequin body that was viewed from a third-person perspective through a mirror, from a third-person perspective without a mirror, and from a first-person perspective. In contrast to non-mirror third-person perspective, synchronously touching the participant's actual body and the mannequin body viewed in the mirror elicited strong feelings of ownership over the mannequin and increased physiological responses to the mannequin being threatened compared to the equivalent asynchronous (non-ownership) control condition. Subjective reports of ownership viewing the mannequin through a mirror were also statistically equivalent to those following the first-person perspective illusion. These findings suggest that mirrors have a special role for viewing the self. The results also support the importance of egocentric reference frames for body ownership and suggest that mirror reflections of one's own body are related to peripersonal space, which enables updating of central body representations. PMID- 26678092 TI - Toward the suppression of cellular toxicity from single-walled carbon nanotubes. AB - In the multidisciplinary fields of nanobiology and nanomedicine, single-walled carbon nanotubes (SWCNTs) have shown great promise due to their unique morphological, physical and chemical properties. However, understanding and suppressing their cellular toxicity is a mandatory step before promoting their biomedical applications. In light of the flourishing recent literature, we provide here an extensive review on SWCNT cellular toxicity and an attempt to identify the key parameters to be considered in order to obtain SWCNT samples with minimal or no cellular toxicity. PMID- 26678093 TI - Mechanism for attenuated outward conductance induced by mutations in the cytoplasmic pore of Kir2.1 channels. AB - Outward currents through Kir2.1 channels regulate the electrical properties of excitable cells. These currents are subject to voltage-dependent attenuation by the binding of polyamines to high- and low-affinity sites, which leads to inward rectification, thereby controlling cell excitability. To examine the effects of positive charges at the low-affinity site in the cytoplasmic pore on inward rectification, we studied a mutant Kir channel (E224K/H226E) and measured single channel currents and streaming potentials (Vstream), the latter provide the ratio of water to ions queued in a single-file permeation process in the selectivity filter. The water-ion coupling ratio was near one at a high K(+) concentration ([K(+)]) for the wild-type channel and increased substantially as [K(+)] decreased. On the other hand, fewer ions occupied the selectivity filter in the mutant at all [K(+)]. A model for the Kir channel involving a K(+) binding site in the wide pore was introduced. Model analyses revealed that the rate constants associated with the binding and release to and from the wide-pore K(+) binding site was modified in the mutant. These effects lead to the reduced contribution of a conventional two-ion permeation mode to total conductance, especially at positive potentials, thereby inward rectification. PMID- 26678095 TI - CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value. AB - CD123 is the alpha-subunit of the interleukin-3 receptor; it represents a potential therapeutic target in systemic mastocytosis (SM) given its absent expression on normal/reactive mast cells (MCs) and aberrant expression on neoplastic MCs. We studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. Two hematopathologists independently scored bone marrow slides using predefined histologic parameters. In all, 23 patients had indolent SM (ISM), 10 aggressive SM (ASM), 23 SM with associated hematological neoplasm (SM-AHN) and 2 had mast cell leukemia (MCL). MC_CD123 expression was demonstrable in 37 (64%) cases; expression rates were 100%, 61%, 57% and 0% in ASM, ISM, SM-AHN and MCL, respectively (P=0.02). Focal proliferation of plasmacytoid dendritic cells (PDCs) around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 (76%) cases, and was significantly higher in CD123-positive versus -negative cases (87% versus 50%, P=0.005). CD123 expression and its staining intensity had prognostic value in SM chronic myelomonocytic leukemia and nonindolent SM patients, respectively. These observations suggest that targeting CD123 in SM may have direct (via MCs) and indirect (via PDCs) antitumor effects and clinical trials to that effect require laboratory correlative studies to address the observed target expression heterogeneity. PMID- 26678096 TI - Facile synthesis of magnetic hierarchical copper silicate hollow nanotubes for efficient adsorption and removal of hemoglobin. AB - This study reports the fabrication of magnetic copper silicate hierarchical hollow nanotubes, which are featured by a tailored complex wall structure and high surface area. Moreover, they exhibit excellent performance as an easily recycled adsorbent for protein separation. Particularly, this strategy can be extended as a general method to prepare other magnetic metal silicate hollow nanotubes. PMID- 26678094 TI - A rapid and affordable screening platform for membrane protein trafficking. AB - BACKGROUND: Membrane proteins regulate a diversity of physiological processes and are the most successful class of targets in drug discovery. However, the number of targets adequately explored in chemical space and the limited resources available for screening are significant problems shared by drug-discovery centers and small laboratories. Therefore, a low-cost and universally applicable screen for membrane protein trafficking was developed. RESULTS: This high-throughput screen (HTS), termed IRFAP-HTS, utilizes the recently described MarsCy1-fluorogen activating protein and the near-infrared and membrane impermeant fluorogen SCi1. The cell surface expression of MarsCy1 epitope-tagged receptors can be visualized by simple addition of SCi1. User-friendly, rapid, and quantitative detection occurs on a standard infrared western-blotting scanner. The reliability and robustness of IRFAP-HTS was validated by confirming human vasopressin-2 receptor and dopamine receptor-2 trafficking in response to agonist or antagonist. The IRFAP-HTS screen was deployed against the leucine-rich G protein-coupled receptor 5 (Lgr5). Lgr5 is expressed in stem cells, modulates Wnt/beta-catenin signaling, and is therefore a promising drug target. However, small molecule modulators have yet to be reported. The constitutive internalization of Lgr5 appears to be one primary mode through which its function is regulated. Therefore, IRFAP-HTS was utilized to screen 11,258 FDA-approved and drug-like small molecules for those that antagonize Lgr5 internalization. Glucocorticoids were found to potently increase Lgr5 expression at the plasma membrane. CONCLUSION: The IRFAP-HTS platform provides a versatile solution for screening more targets with fewer resources. Using only a standard western-blotting scanner, we were able to screen 5,000 compounds per hour in a robust and quantitative assay. Multi-purposing standardly available laboratory equipment eliminates the need for idiosyncratic and more expensive high-content imaging systems. The modular and user-friendly IRFAP-HTS is a significant departure from current screening platforms. Small laboratories will have unprecedented access to a robust and reliable screening platform and will no longer be limited by the esoteric nature of assay development, data acquisition, and post-screening analysis. The discovery of glucocorticoids as modulators for Lgr5 trafficking confirms that IRFAP-HTS can accelerate drug-discovery and drug-repurposing for even the most obscure targets. PMID- 26678097 TI - Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity. AB - Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism based biomarkers which provide insight into or drug molecular mechanisms of action (MoA). PMID- 26678099 TI - Fat Grafting for Neuropathic Pain After Severe Burns. AB - BACKGROUND: Chronic neuropathic pain after burn injury is a significant problem that affects up to 29% of burn patients. Neuropathic burn scar pain is a challenge for plastic and burn surgeons, who have limited solutions. Fat grafting, with its mechanical and regenerative qualities, can improve neuropathic pain from various traumatic and postsurgical etiologies, but its effectiveness in neuropathic burn scar pain has yet to be demonstrated. In this study, the possible role of lipotransfer in treating neuropathic burn scar pain is explored, focusing on safety, graft take, and short-term efficacy. METHODS: We performed an institutional review board-approved, retrospective case review of 7 patients with chronic, refractory neuropathic pain, who underwent fat grafting to burn scars. These patients had failed conventional therapy, which included pharmacologic, medical, and laser treatment of the burn scars. Each patient had 2 sessions of fat grafting, spaced 2 months apart. The Patient-Reported Outcomes Measurement Information System (PROMIS) was used to assess pain perception, with patients answering the questionnaire before and after fat grafting, to assess subjective outcomes. RESULTS: Six of 7 patients had improvement in neuropathic pain after fat grafting, permitting reduction in their neuropharmacologic regimen. Tinel sign, present in all patients preoperatively, was absent on examination in all patients at follow-up. Three of the 5 patients who completed PROMIS questionnaires had PROMIS scores indicating improvement in pain by 1-year follow up. One patient had similar preoperative and postoperative PROMIS scores, and 1 patient had an increase in pain at follow-up; however, he had suffered an additional burn to the same extremity. Analysis of pooled mean PROMIS scores reflects a statistically significant improvement in subjective outcomes by 1-year follow-up. Donor-site seroma in 1 patient was the only complication, with no cases of infection, wound breakdown, or graft loss. CONCLUSIONS: Adipose tissue can be safely grafted into burn scars and may improve symptoms in patients with refractory neuropathic pain after burn injury. Further translational and clinical research is necessary to elucidate mechanisms of action, indications, optimal type of transfer, and long-term effectiveness. PMID- 26678098 TI - Association of Interleukin-23 receptor gene polymorphisms with susceptibility to Crohn's disease: A meta-analysis. AB - Studies investigating the association between Interleukin-23 receptor (IL-23R) gene polymorphisms and Crohn's disease (CD) report conflicting results. Thus, a meta-analysis was carried out to assess the association between the IL-23R polymorphisms and CD. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CIs) was used to estimate the strength of association. Finally, a total of 60 case control studies in 56 articles, involving 22,820 CD patients and 27,401 healthy controls, were included in the meta-analysis. Overall, a significant association was found between all CD and the rs7517847 polymorphism (OR = 0.699, 95% CI = 0.659 ~ 0.741, P < 0.001). Meta-analysis of the rs11209026, rs1343151, rs10489629 and rs11465804 polymorphisms indicated the same pattern as for rs7517847. Meta analysis showed an association between the rs10889677A allele and CD (OR = 1.393, 95% CI = 1.328 ~ 1.461, P < 0.001). Similarly, meta-analysis of the rs2201840, rs1004819, rs1495965 and rs11209032 polymorphisms revealed the same pattern as that shown by meta-analysis of rs10889677. Stratification by ethnicity revealed that IL-23R gene polymorphisms were associated with CD in the Caucasian group, but not in Asians. In summary, the meta-analysis suggests a significant association between IL-23R polymorphisms and CD, especially in Caucasians. PMID- 26678100 TI - The Effect of Financial Conflicts of Interest in Plastic Surgery Literature. AB - Medical research has a long history of joint venture between commercial entities and nonindustry researchers. Significant concern exists among accrediting bodies for medical education and federal granting agencies that conflicts of interest (COIs) exist that affect the validity of the research. This study evaluates the legitimacy of this concern.All clinical breast and cosmetic articles in Plastic and Reconstructive Surgery and Annals of Plastic Surgery were reviewed for calendar year 2013. If a financial disclosure was present, the article was then reviewed to determine if the subject/findings were in favor of the commercial conflict and, if so, whether the study was valid. To assess plastic surgery versus other specialties, articles from Dermatology and Journal of Bone and Joint Surgery were similarly reviewed from January to April of 2013.Two hundred seventy two clinical articles were reviewed. Only 15 (5.5%) had a true COI: the article's findings favored the commercial interest of at least 1 author: for each journal, Plastic and Reconstructive Surgery, 7.7%; Annals of Plastic Surgery, 3.3%; Dermatology, 2.2%; Journal of Bone and Joint Surgery, 7.5%. Conflicts of interest were not statistically significant between pooled articles of plastic surgery versus dermatology/orthopedics. However, COI was statistically greater (P = 0.05) in Plastic and Reconstructive Surgery compared with Annals and Dermatology.Despite public and regulatory concerns, this assessment demonstrates that the peer-review process of leading journals polices true COIs. Published articles provide sound research despite presumed COIs. As such, the integrity and validity of published research remain high. PMID- 26678101 TI - Short-Scar Mammaplasty in Severe Macromastia. AB - It is generally claimed that short-scar mammaplasty is limited to small-to-medium reductions. Its use in patients with severe macromastia has been associated with a high rate of complications. This report presents our experience of reduction mammaplasty greater than 1000 g per breast using a short-scar technique. The procedure is based on the following: a) modified breast marking method with conservative placement of the nipple-areola complex, determined not only by the level of the inframammary fold but also degree of upper pole volume loss; b) use of liposuction for contouring the inferior pole; c) vertical design dermoglandular resection; d) superomedial pedicle; and e) skin closure without undermining or gathering. A total of 69 patients were identified (n = 138 breasts). Mean age was 38.0 years with average BMI of 36.4 kg/m. Mean weight of breast removed was 1333.8 g (range, 1002-3275). New nipple position was determined to be inferior to the inframammary fold at a mean distance of 4.6 cm, as predicted by the degree of flatness of upper pole. Complications included delayed healing (7.2%), fat necrosis (10.1%), infection (5.8%), hematoma (2.9%), and seroma (1.5%). There were no instances of nipple-areola complex necrosis. Revision of dog-ears was necessary in 7 patients (10.1%). The authors conclude that in using a modified short-scar mammaplasty approach in cases of severe macromastia, the outcomes can be improved with reduced scar burden, pleasing breast shape, and a low complication rate. PMID- 26678102 TI - Aesthetic and Functional Outcome of Zygomatic Fractures Fixation Comparison With Resorbable Versus Titanium Plates. AB - OBJECTIVE: The study compares resorbable versus titanium fixation systems for their aesthetic and functional outcome in the treatment of zygomatic fractures. METHODS: Twenty-seven patients who required operative reduction and internal fixation for zygomatic fractures were studied in the period from April 2007 to March 2008. Fourteen patients who had fixation with resorbable plate/screws (group A) were compared with 13 patients fixed with titanium plates/screws (group B). The aesthetic outcome was evaluated by an overall self-satisfaction score at 2, 4, and 6 weeks and then at 6 months and 1 year postoperative interval, and the degree of displacement from computed tomographic facial bones were compared preoperatively and 1 year postoperatively. The functional outcome was evaluated by a self-satisfaction scoring system and maximum mouth opening during the same time intervals. RESULTS: The outcome showed that the 2 groups were matched in age, sex ratio, fracture severity, total displacement with 5 sutures, and aesthetic scores preoperatively (P > 0.05). The subjective evaluation by patients for functional satisfaction and overall satisfaction all showed lower satisfaction of absorbable group when compared to titanium group within a postoperative 4-week period, but the satisfaction was similar for both groups after 4 weeks. There was no significant difference between the 2 groups at each measured time period. Postoperative total displacement and aesthetic score demonstrated great improvement in fracture reduction and long-term stability in both groups. CONCLUSION: There is no significant difference in the outcome between resorbable and titanium plates/screws in fixation of zygomatic fractures. These findings together with the advantages of biodegradable fixation validate its use in fixing these fractures with minimal morbidity. PMID- 26678103 TI - Fat Grafting for Recontouring Sunken Upper Eyelids With Multiple Folds in Asians Novel Mechanism for Neoformation of Double Eyelid Crease. AB - BACKGROUND: This study reviewed the mini invasive technique, microautologous fat transplantation (MAFT), as a strategy in simultaneously treating sunken upper eyelids with multiple folds and recreating a double eyelid crease in Asian people. METHODS: The MAFT was performed with the assistance of a patented medical device, the MAFT-GUN, on 34 patients who had sunken upper eyelids and multiple folds. Each delivered fat parcel was accurately and consistently maintained at 1/240 mL during placement. Follow-up was regularly performed with photography for comparison. RESULTS: Fifty-eight sunken upper eyelids with multiple folds were reconstructed. In addition to the ameliorative recontouring of hollowness, a natural eyelid crease was created postoperatively. Temporary swelling and bruising were noted several days after surgery without morbidities, such as fibrosis or nodulation. All of the patients were satisfied with the 1-time MAFT procedure. CONCLUSIONS: Fat grafting for sunken upper eyelids with multiple folds has been reported in the literature. However, temporal effects and complications, such as nodulation and irregularity, have often occurred. A new method, MAFT, demonstrated its reliability as a modality for sunken upper eyelids with multiple folds in Asians. Moreover, MAFT might serve as an alternative for neoformation of double eyelids in these candidates. PMID- 26678104 TI - Three-Dimensional Printing in Plastic and Reconstructive Surgery: A Systematic Review. AB - BACKGROUND: Increasingly affordable three-dimensional (3D) printing technologies now make it possible for surgeons to create highly customizable patient-tailored products. This process provides the potential to produce individualized artificial and biologic implants, regenerative scaffolds, and cell-specific replacement tissue and organs. The combination of accurate volumetric analysis and production of 3D printed biologic materials are evolving techniques that demonstrate great promise in achieving an accurate and naturally appearing anthropomorphic reconstruction. This systematic review summarizes the current published literature and known ongoing research on 3D printing in the field of plastic and reconstructive surgery (PRS). METHODS: Three medical databases (PubMed, Ovid MEDLINE, and Google Scholar) as well as recent news articles and university websites were searched using PRS and industry-related search terms. Inclusion criteria consisted of any publication or reputable news or academic article in electronic or printed media directly studying or commenting on the use of 3D printing technology in relation to PRS. The current literature was critically appraised, and quality of selected articles was assessed and manually filtered for relevance by 2 reviewers. RESULTS: A total of 1092 articles were identified from the aforementioned sources discussing 3D printing in medicine. The 3D printing in relation to biologic and surgical applications was discussed in 226 articles. Within this subset, 103 articles were included in the review. Of those selected, 5 were pertinent to surgical planning, training, and patient education; 4 to upper extremity and hand prosthetics; 24 to bone and craniomaxillofacial (CMF) reconstruction; 10 to breast reconstruction; 20 to nose, ear, and cartilage reconstruction; 20 to skin; and finally 20 involving overlapping general topics in 3D printing and PRS. CONCLUSIONS: The 3D printing provides the ability to construct complex individualized implants that not only improve patient outcomes but also increase economic feasibility. The technology offers a potential level of accessibility that is paramount for remote and resource-limited locations where health care is most often limited. The 3D printing-based technologies will have an immense impact on the reconstruction of traumatic injuries, facial and limb prosthetic development, as well as advancements in biologic and synthetic implants. PMID- 26678105 TI - Reverse Radial Artery Flap Perforator Anatomy and Clinical Applications. AB - The pedicled reverse radial forearm flap is a well-known option for the treatment of a variety of soft tissue wounds including dorsal hand wounds. We document the number, emerging diameter, length from origin, course, and location of all perforators of the radial artery in a series of 6 fresh human cadavers after whole body lead oxide and gelatin injection to confirm and comprehensively document the anatomy of the radial artery perforators. This data provide an anatomic basis for a modification to the reversed radial forearm flap used to decrease venous congestion in the postoperative period. Two case reports are presented to provide clinical demonstration of the importance of this modification. PMID- 26678106 TI - Outcomes of Breast Reconstruction After Mastectomy Using Tissue Expander and Implant Reconstruction. AB - OBJECTIVE: Considerable attention has been given to patient-reported outcomes in breast reconstruction. The objective of this study is to evaluate the effect of postreconstruction change in breast volume on validated patient satisfaction survey scores. METHODS: Patients undergoing skin-sparing mastectomy followed by tissue expander/implant reconstruction between July 2010 and July 2014 by a single surgeon were given postoperative patient-reported satisfaction surveys (BREAST-Q). Retrospective chart review of patients with completed surveys was undertaken to record patient characteristics and compare preoperative breast volume (extrapolated from mastectomy mass) with postoperative implant volume, and percent change in volume was calculated. Regressions were utilized to correlate percent change with satisfaction in each category. RESULTS: A total of 160 patient surveys were included. Sixty-five percent of breasts analyzed had increased volume after reconstruction, whereas 35% had decreased volume. The increased volume group had significantly lower body mass index (P = 0.0001) and was significantly younger (P = 0.009) than the decreased volume group. Patients who experienced increase in breast volume reported statistically greater satisfaction with breasts (P = 0.019), overall outcome (P = 0.012), sexual well being (P = 0.002), and information (P = 0.042) compared with the decreased volume group. Moreover, linear regression revealed that as percent change increased, so did satisfaction with outcome (P = 0.02), sexual well-being (P = 0.005), information (P = 0.018), and surgeon (P = 0.036). Notably, there was not a significant difference in complication rate (P = 0.146) or tumor margin (0.914) between the groups. CONCLUSION: Patients who undergo tissue expander/implant breast reconstruction with final implants that are larger in volume than their native breasts have increased patient satisfaction scores in several categories without increase in complication rate or difference in tumor margin. There is a positive linear relationship between percent change and patient satisfaction. PMID- 26678120 TI - Development of risk-based trading farm scoring system to assist with the control of bovine tuberculosis in cattle in England and Wales. AB - Identifying and ranking cattle herds with a higher risk of being or becoming infected on known risk factors can help target farm biosecurity, surveillance schemes and reduce spread through animal trading. This paper describes a quantitative approach to develop risk scores, based on the probability of infection in a herd with bovine tuberculosis (bTB), to be used in a risk-based trading (RBT) scheme in England and Wales. To produce a practical scoring system the risk factors included need to be simple and quick to understand, sufficiently informative and derived from centralised national databases to enable verification and assess compliance. A logistic regression identified herd history of bTB, local bTB prevalence, herd size and movements of animals onto farms in batches from high risk areas as being significantly associated with the probability of bTB infection on farm. Risk factors were assigned points using the estimated odds ratios to weight them. The farm risk score was defined as the sum of these individual points yielding a range from 1 to 5 and was calculated for each cattle farm that was trading animals in England and Wales at the start of a year. Within 12 months, of those farms tested, 30.3% of score 5 farms had a breakdown (sensitivity). Of farms scoring 1-4 only 5.4% incurred a breakdown (1 specificity). The use of this risk scoring system within RBT has the potential to reduce infected cattle movements; however, there are cost implications in ensuring that the information underpinning any system is accurate and up to date. PMID- 26678121 TI - Frequency Characteristics in Animal Species Typically Used in Laryngeal Research: An Exploratory Investigation. AB - OBJECTIVES: Laryngeal research is typically conducted on animal species that have similar features to the human larynx, yet little is known of the frequency characteristics of those animals. This study examines frequency characteristics of dog, cat, pig, and sheep across emotional communication events. STUDY DESIGN: Prospective study. METHODS: Acoustic data were gathered in domestic environment, with fundamental frequency (fo) computation of vocalization during happy, distress, and food request activities. RESULTS: Dogs demonstrated reduced fo range and reduced vocalization as a factor of age (18 semitones for adult male dog, three semitones for aged male dog). When two barks were present, the second bark was typically shorter in length and had a higher fo. Male cat was observed to be more talkative and exhibited a much higher purr fo than his female housemate. Cat purr was varied by sex between the typical 25 Hz and a significantly higher fo, consistent with literature on use of cry-purr by some cats. Lambs exhibited phonation breaks, and an overall frequency range of 28 semitones in lambs compared with 49 semitones for mature sheep. Piglets exhibited fo range of 44 semitones with higher fo with distress and lowest fo for grunting. CONCLUSIONS: Aged animals followed similar phonatory patterns of humans, with change of fo for communication need. The male cat was found to purr differently from female cats. Pigs and cats may have nonlaryngeal source signal coupling. Animal phonation changes with emotion. Observed fo patterns may improve interpretation of phonation among laboratory animals in laryngeal research. PMID- 26678122 TI - Effects on Voice Fundamental Frequency and Satisfaction with Voice in Trans Men during Testosterone Treatment-A Longitudinal Study. AB - OBJECTIVES: To investigate effects of testosterone treatment regarding voice virilization, voice problems, and voice satisfaction in transsexual female-to male individuals, referred to as trans men. STUDY DESIGN: Longitudinal. METHODS: Fifty trans men, diagnosed with transsexualism, 18-64 years, met the inclusion criteria. Voice data before treatment and after 3, 6, or 12 months were available from 49 participants, and for 28 participants also after 18 and/or 24 months of treatment. Digital audio recordings of speech range profiles and voice range profiles were carried out in a sound-treated booth following clinical routines. Acoustic analyses of fundamental frequency (F0) and sound pressure level were made. Endocrine data and answers from questionnaires concerning voice function and voice problems were collected from medical records. RESULTS: Mean F0 and mode F0 of the habitual voice decreased significantly after 3 months, 6 months, and up to 12 months, when group data were congruent with reference data for males. Mean F0 was 125 Hz after 12 months with a large interindividual variation. Sound pressure level values did not change significantly. Voice satisfaction correlated with lower F0 values. Twenty-four percent of the participants reported voice symptoms, for example, vocal instability and fatigue, and had received voice therapy. F0 values did not correlate with androgen levels. CONCLUSIONS: Most trans men developed a male voice and were satisfied. However, it is important to detect the substantial group of trans men with voice problems and with insufficient voice virilization and who may need voice therapy. Therefore, we recommend systematic voice assessments during testosterone treatment. PMID- 26678123 TI - Using physical approaches for the attenuation of lactic acid bacteria in an organic rice beverage. AB - A wild strain of Lactobacillus plantarum, isolated from an Italian sourdough, was inoculated in an organic rice drink; however, it caused a strong acidification. Thus, it was preliminary processed through homogenization (single or multiple passes) or sonication (US) and then inoculated in the beverage. The samples were stored at 4 degrees C and analyzed to assess pH, production of lactic acid, viable count and sensory scores. A US-2-step process (power, 80%) could control acidification; viability and sensory traits were never affected by sonication. This result was confirmed on two commercial probiotics (Lactobacillus casei LC01 and Bifidobacterium animalis subsp. lactis Bb12). In the 2nd step samples inoculated with attenuated strains were also stored under thermal abuse conditions (25 or 37 degrees C for 4 or 24 h, then at 4 degrees C) and the results showed that US could control acidification for a short thermal abuse. Finally, US-attenuated starter cultures were inoculated in the rice drink containing beta-glucans as healthy compounds; the targets did not cause any significant change of prebiotic. PMID- 26678124 TI - Effect of sequential dry heat and hydrogen peroxide treatment on inactivation of Salmonella Typhimurium on alfalfa seeds and seeds germination. AB - The purpose of this study was to inactivate Salmonella Typhimurium on alfalfa seeds without having negative effect on seed germination. Inoculated alfalfa seeds were treated with dry heat at 60, 70 or 80 degrees C for 0, 12, 18 or 24 h followed by 2% hydrogen peroxide solution (10 min). Populations of Salmonella on alfalfa seeds treated with dry heat alone (60, 70 or 80 degrees C) for up to 24 h were reduced by 0.26-2.76 log CFU/g, and sequential treatment with dry heat and H2O2 reduced populations by 1.66-3.60 log CFU/g. The germination percentage of seeds subjected to sequential treatments was significantly enhanced to up to 97%, whereas that of untreated seeds was only 79.5%. This study suggests that sequential treatment with dry heat and hydrogen peroxide is applicable for reducing levels of Salmonella on seeds while simultaneously enhancing seeds germinability. PMID- 26678125 TI - Spoilage of vacuum-packed beef by the yeast Kazachstania psychrophila. AB - A survey of the psychrotolerant yeast microbiota of vacuum-packed beef was conducted between 2010 and 2012. Chilled vacuum-packed beef (n = 50) sampled from 15 different producers was found to have a mean psychrotolerant yeast count of 3.76 log cfu per cm(2). During this assessment, a recently described yeast named Kazachstania psychrophila was shown to be associated with this product. In order to gain basic knowledge about the spoilage potential of K. psychrophila in vacuum packed beef, challenge studies were performed and the survival of three different K. psychrophila strains was analyzed during storage of artificially contaminated beef. Beef samples were inoculated with the yeasts at a contamination level of 2 log cfu per cm(2). Survival and growth of K. psychrophila strains was monitored on malt extract agar at regular intervals over 84 days. Kazachstania levels rapidly increased about 5 log units within 16 days under chill conditions (4 degrees C). Gas bubbles were observed after 16 days, while discoloration and production of off-flavors became evident after 42 days in inoculated samples. This study demonstrates for the first time, that the psychrotolerant yeast K. psychrophila is a dominant spoilage microorganism of vacuum-packed beef products stored at low temperatures, causing sensory defects which result in reduced shelf life, and consequently in considerable economic losses. PMID- 26678126 TI - Evidence for synergistic activity of plant-derived essential oils against fungal pathogens of food. AB - The antifungal activities of eight essential oils (EOs) namely basil, cinnamon, eucalyptus, mandarin, oregano, peppermint, tea tree and thyme were evaluated for their ability to inhibit growth of Aspergillus niger, Aspergillus flavus, Aspergillus parasiticus and Penicillium chrysogenum. The antifungal activity of the EOs was assessed by the minimum inhibitory concentration (MIC) using 96-well microplate analysis. The interactions between different EO combinations were done by the checkerboard technique. The highest antifungal activity was exhibited by oregano and thyme which showed lower MIC values amongst all the tested fungi. The antifungal activity of the other EOs could be appropriately ranked in a descending sequence of cinnamon, peppermint, tea tree and basil. Eucalyptus and mandarin showed the least efficiency as they could not inhibit any of the fungal growth at 10,000 ppm. The interaction between these two EOs also showed no interaction on the tested species. A combined formulation of oregano and thyme resulted in a synergistic effect, showing enhanced efficiency against A. flavus and A. parasiticus and P. chrysogenum. Mixtures of peppermint and tea tree produced synergistic effect against A. niger. Application of a modified Gompertz model considering fungal growth parameters like maximum colony diameter, maximum growth rate and lag time periods, under the various EO treatment scenarios, showed that the model could adequately describe and predict the growth of the tested fungi under these conditions. PMID- 26678127 TI - Enological characterization of Spanish Saccharomyces kudriavzevii strains, one of the closest relatives to parental strains of winemaking and brewing Saccharomyces cerevisiae * S. kudriavzevii hybrids. AB - Wine fermentation and innovation have focused mostly on Saccharomyces cerevisiae strains. However, recent studies have shown that other Saccharomyces species can also be involved in wine fermentation or are useful for wine bouquet, such as Saccharomyces uvarum and Saccharomyces paradoxus. Many interspecies hybrids have also been isolated from wine fermentation, such as S. cerevisiae * Saccharomyces kudriavzevii hybrids. In this study, we explored the genetic diversity and fermentation performance of Spanish S. kudriavzevii strains, which we compared to other S. kudriavzevii strains. Fermentations of red and white grape musts were performed, and the phenotypic differences between Spanish S. kudriavzevii strains under different temperature conditions were examined. An ANOVA analysis suggested striking similarity between strains for glycerol and ethanol production, although a high diversity of aromatic profiles among fermentations was found. The sources of these phenotypic differences are not well understood and require further investigation. Although the Spanish S. kudriavzevii strains showed desirable properties, particularly must fermentations, the quality of their wines was no better than those produced with a commercial S. cerevisiae. We suggest hybridization or directed evolution as methods to improve and innovate wine. PMID- 26678128 TI - Conventional curing practices reduce generic Escherichia coli and Salmonella spp. on dry bulb onions produced with contaminated irrigation water. AB - Food Safety Modernization Act (FSMA) has emphasized microbial risks associated with irrigation water. Treasure Valley (eastern Oregon/western Idaho) has the highest yield of dry bulb onions in the country; however, their irrigation water is often non-compliant with current industry and proposed federal standards for fresh produce. Conventional curing practices may provide a mechanism to mitigate irrigation water quality to comply with FSMA regulations. Dry bulb onions were grown in Owyhee silt loam and Semiahmoo muck soils in greenhouses and irrigated with water containing a cocktail of rifampicin-resistant generic Escherichia coli and Salmonella spp. (4.80 log CFU/ml). To mimic conventional practices, mature onions remained undisturbed in soil without irrigation for 12 days prior to being lifted and cured for 16 additional days. Surviving generic E. coli and Salmonella spp. were selectively enumerated on using standard plating (Hektoen Enteric Agar with rifampicin; HE + rif) or most probable number (lactose broth with rifampicin; HE + rif) methods. Generic E. coli and Salmonella spp. on onions decreased 0.19-0.26 log CFU/g.d during the initial 12 days of finishing. At lifting, generic E. coli and Salmonella spp. had been reduced to <1 CFU/g and persisted through the end of curing. This study demonstrates conventional curing practices as an effective mitigation strategy for dry bulb onions produced with water of poor microbiological quality. PMID- 26678129 TI - Inactivation of Salmonella Senftenberg, Salmonella Typhimurium and Salmonella Tennessee in peanut butter by 915 MHz microwave heating. AB - This study evaluated the efficacy of a 915 MHz microwave with 3 different levels to inactivate 3 serovars of Salmonella in peanut butter. Peanut butter inoculated with Salmonella enterica serovar Senftenberg, S. enterica serovar Typhimurium and S. enterica serovar Tennessee were treated with a 915 MHz microwave with 2, 4 and 6 kW and acid and peroxide values and color changes were determined after 5 min of microwave heating. Salmonella populations were reduced with increasing treatment time and treatment power. Six kW 915 MHz microwave treatment for 5 min reduced these three Salmonella serovars by 3.24-4.26 log CFU/g. Four and two kW 915 MHz microwave processing for 5 min reduced these Salmonella serovars by 1.14 1.48 and 0.15-0.42 log CFU/g, respectively. Microwave treatment did not affect acid, peroxide, or color values of peanut butter. These results demonstrate that 915 MHz microwave processing can be used as a control method for reducing Salmonella in peanut butter without producing quality deterioration. PMID- 26678130 TI - Diversity and enumeration of halophilic and alkaliphilic bacteria in Spanish style green table-olive fermentations. AB - The presence and enumeration of halophilic and alkaliphilic bacteria in Spanish style table-olive fermentations was studied. Twenty 10-tonne fermenters at two large manufacturing companies in Spain, previously studied through both culture dependent and independent (PCR-DGGE) methodologies, were selected. Virtually all this microbiota was isolated during the initial fermentation stage. A total of 203 isolates were obtained and identified based on 16S rRNA gene sequences. They belonged to 13 bacterial species, included in 11 genera. It was noticeable the abundance of halophilic and alkaliphilic lactic acid bacteria (HALAB). These HALAB belonged to the three genera of this group: Alkalibacterium, Marinilactibacillus and Halolactibacillus. Ten bacterial species were isolated for the first time from table olive fermentations, including the genera Amphibacillus, Natronobacillus, Catenococcus and Streptohalobacillus. The isolates were genotyped through RAPD and clustered in a dendrogram where 65 distinct strains were identified. Biodiversity indexes found statistically significant differences between both patios regarding genotype richness, diversity and dominance. However, Jaccard similarity index suggested that the halophilic/alkaliphilic microbiota in both patios was more similar than the overall microbiota at the initial fermentation stage. Thus, up to 7 genotypes of 6 different species were shared, suggesting adaptation of some strains to this fermentation stage. Morisita-Horn similarity index indicated a high level of codominance of the same species in both patios. Halophilic and alkaliphilic bacteria, especially HALAB, appeared to be part of the characteristic microbiota at the initial stage of this table-olive fermentation, and they could contribute to the conditioning of the fermenting brines in readiness for growth of common lactic acid bacteria. PMID- 26678131 TI - Control of Shigatoxin-producing Escherichia coli in cheese by dairy bacterial strains. AB - Bio-preservation could be a valuable way to control Shigatoxin-producing Escherichia coli (STEC) in cheese. To this end, 41 strains were screened for their inhibitory potential on model cheese curd and on pasteurized and raw milk uncooked pressed cheeses. Strains of Lactococcus lactis, Lactococcus garvieae, Leuconostoc pseudomesenteroides, Leuconostoc citreum, Lactobacillus sp, Carnobacterium mobile, Enterococcus faecalis, Enterococcus faecium, Macrococcus caseolyticus and Hafnia alvei reduced STEC O26:H11 counts by 1.4-2.5 log cfu g( 1) and to a lesser extent STEC O157:H7 counts in pasteurized milk cheeses. Some strains can act in synergy to inhibit STEC in raw milk uncooked pressed cheeses. Inhibitory associations had no adverse effect on the sensory characteristics of these cheeses. The association of H. alvei, Lactobacillus plantarum and Lc. lactis was the most inhibitory: after inoculation of this consortium into milk, STEC O26:H11 and O157:H7, inoculated at 2 log cfu ml(-1), were reduced by up to 3 log cfu g(-1) in ripened cheese. Inhibition in cheese cannot be predicted from H2O2 production in BHI medium, decreased pH or milk reduction. It is not clear what role the rapid decrease in pH during the first 6 h may play in the inhibition. Further studies will be needed to determine the nature of the inhibition. PMID- 26678132 TI - Survival of potential probiotic lactic acid bacteria on fermented green table olives during packaging in polyethylene pouches at 4 and 20 degrees C. AB - The survival of selected lactic acid bacteria (LAB) with in vitro probiotic potential was studied during storage of cv. Halkidiki green olives previously subjected to inoculated Spanish-style fermentation. After fermentation olives were packed in polyethylene pouches, covered with freshly prepared brine (9%, w/v, NaCl), acidified with 20/00 (w/v) citric acid and 1.50/00 (w/v) ascorbic acid, and stored at 4 and 20 degrees C for 357 days. Four packing treatments were studied, namely olives previously fermented by (i) the indigenous microbiota (control); (ii) Lactobacillus pentosus B281; (iii) Lactobacillus plantarum B282; and (iv) a co-culture of both LAB strains. Microbiological analyses were performed on the olives in parallel with physicochemical changes (pH, titratable acidity, salt content, aw and colour) at the early (day 1), middle (day 197) and final stage (day 357) of storage, as well as sensory evaluation at the end of the storage. The survival of probiotic strains was confirmed by Pulsed Field Gel Electrophoresis (PFGE). LAB decreased throughout storage reaching a final population of ca. 3.5-4.0 log CFU/g and 4.5-5.0 log CFU/g at 4 and 20 degrees C, respectively. The pH values ranged between 3.90 and 4.61 during storage depending on packaging condition. PFGE analysis revealed that L. pentosus B281 and L. plantarum B282 showed a high survival rate with a recovery of 100 and 96%, respectively, at 4 degrees C, and less than 20% for both strains at 20 degrees C. Finally, in the packing treatment with a co-culture of both strains, L. pentosus dominated over L. plantarum throughout storage at both temperatures. PMID- 26678133 TI - Modelling biofilm formation of Salmonella enterica ser. Newport as a function of pH and water activity. AB - The effect of pH and water activity (aw) on the formation of biofilm by Salmonella enterica ser. Newport, previously identified as a strong biofilm producer, was assessed. Biofilm formation was evaluated in tryptone soy broth at 37 degrees C and at different combinations of pH (3.3-7.8) and aw (0.894-0.997). In total, 540 biofilm formation tests in 108 pH and aw combinations were carried out in polystyrene microtiter plates using crystal violet staining and optical density (OD; 580 nm) measurements. Since the individual effects of pH and aw on biofilm formation had a similar pattern to that observed for microbial growth rate, cardinal parameter models (CPMs) were used to describe these effects. CPMs described successfully the effects of these two environmental parameters, with the estimated cardinal values of pHmin, pHopt, pHmax, awmin and awopt being 3.58, 6.02, 9.71, 0.894 and 0.994, respectively. The CPMs assumption of the multiplicative inhibitory effect of environmental factors was validated in the case of biofilm formation using additional independent data (i.e. 430 OD data at 86 different combinations of pH and aw). The validation results showed a good agreement (r(2) = 0.938) between observed and predicted OD with no systematic error. In the second part of this study, a probabilistic model predicting the pathogen's biofilm formation boundaries was developed, and the degree of agreement between predicted probabilities and observations was as high as 99.8%. Hence, the effect of environmental parameters on biofilm formation can be quantitatively expressed using mathematical models, with the latter models, in turn, providing useful information for biofilm control in food industry environments. PMID- 26678134 TI - Egg white versus Salmonella Enteritidis! A harsh medium meets a resilient pathogen. AB - Salmonella enterica serovar Enteritidis is the prevalent egg-product-related food borne pathogen. The egg-contamination capacity of S. Enteritidis includes its exceptional survival capability within the harsh conditions provided by egg white. Egg white proteins, such as lysozyme and ovotransferrin, are well known to play important roles in defence against bacterial invaders. Indeed, several additional minor proteins and peptides have recently been found to play known or potential roles in protection against bacterial contamination. However, although such antibacterial proteins are well studied, little is known about their efficacy under the environmental conditions prevalent in egg white. Thus, the influence of factors such as temperature, alkalinity, nutrient restriction, viscosity and cooperative interactions on the activities of antibacterial proteins in egg white remains unclear. This review critically assesses the available evidence on the antimicrobial components of egg white. In addition, mechanisms employed by S. Enteritidis to resist egg white exposure are also considered along with various genetic studies that have shed light upon egg white resistance systems. We also consider how multiple, antibacterial proteins operate in association with specific environmental factors within egg white to generate a lethal protective cocktail that preserves sterility. PMID- 26678135 TI - Microbial evolution of traditional mountain cheese and characterization of early fermentation cocci for selection of autochtonous dairy starter strains. AB - The microbial population of Traditional Mountain (TM) cheese was investigated and characterized for the selection of cocci suitable for developing new starter cultures. Samples of milk, curd and cheese at different ripening times were enumerated in selective culture media and 640 colonies were isolated from curd and cheese after 24 h of ripening. The Lactic Acid Bacteria (LAB) isolated from M17 were clustered into 231 biotypes by RAPD-PCR analysis and identified as Lactococcus lactis, Streptococcus thermophilus and Enterococcus faecalis. Forty percent of enterococci showed the in vitro ability to inhibit raw milk resident coliforms, but they were excluded as possible starters due to the presence of associated risk factors. All lactococci and streptococci were tested for their technological properties; 4 Lc. lactis subsp. lactis and 2 Sc. thermophilus which were fast acidifiers and did not produce unpleasant flavours were subjected to the freeze-drying stability test. Lc. lactis subsp. lactis biotype 68 and Sc. thermophilus biotype 93 showed the best technological properties and may be appropriate for cheese production. This work gave evidence of the high biodiversity of TM-cheese autochthonous biotypes which could be used as starter cultures for the improvement of TM-cheese technology. PMID- 26678136 TI - Salmonella and Campylobacter: Antimicrobial resistance and bacteriophage control in poultry. AB - Salmonella and Campylobacter are major causes of foodborne related illness and are traditionally associated with consuming undercooked poultry and/or consuming products that have been cross contaminated with raw poultry. Many of the isolated Salmonella and Campylobacter that can cause disease have displayed antimicrobial resistance phenotypes. Although poultry producers have reduced on-the-farm overuse of antimicrobials, antimicrobial resistant Salmonella and Campylobacter strains still persist. One method of bio-control, that is producing promising results, is the use of lytic bacteriophages. This review will highlight the current emergence and persistence of antimicrobial resistant Salmonella and Campylobacter recovered from poultry as well as bacteriophage research interventions and limitations. PMID- 26678137 TI - Lactic acid bacteria in dried vegetables and spices. AB - Spices and dried vegetable seasonings are potential sources of bacterial contamination for foods. However, little is known about lactic acid bacteria (LAB) in spices and dried vegetables, even though certain LAB may cause food spoilage. In this study, we enumerated LAB in 104 spices and dried vegetables products aimed for the food manufacturing industry. The products were obtained from a spice wholesaler operating in Finland, and were sampled during a one-year period. We picked isolates (n = 343) for species identification based on numerical analysis of their ribotyping patterns and comparing them with the corresponding patterns of LAB type strains. We found LAB at levels >2 log CFU/g in 68 (65%) of the samples, with the highest counts detected from dried onion products and garlic powder with counts ranging from 4.24 to 6.64 log CFU/g. The LAB identified were predominantly Weissella spp. (61%) and Pediococcus spp. (15%) with Weissella confusa, Weissella cibaria, Weissella paramesenteroides, Pediococcus acidilactici and Pediococcus pentosaceus being the species identified. Other species identified belonged to the genera of Enterococcus spp. (8%), Leuconostoc spp. (6%) and Lactobacillus spp. (2%). Among the LAB identified, Leuconostoc citreum, Leuconostoc mesenteroides and W. confusa have been associated with food spoilage. Our findings suggest that spices and dried vegetables are potential sources of LAB contamination in the food industry. PMID- 26678138 TI - Development of a model describing the inhibitory effect of selected preservatives on the growth of Listeria monocytogenes in a meat model system. AB - The objective of this study was to evaluate the impact of seven independent factors consisting of sodium nitrite, pH, sodium chloride, sodium acetate, sodium lactate syrup, calcium propionate and a blend of nisin and hop alpha acids on the growth rate of Listeria monocytogenes in ham as a model of ready-to-eat (RTE) meat products. A central composite consisted of seven factors mentioned above was designed and the response surface methodology was applied for creating a mathematic model to predict the growth rate of L. monocytogenes in RTE meat products. Six parameters showed a significant (P <= 0.1) influence on the growth rate of L. monocytogenes. Only the blend of nisin and hop alpha acids did not show any significant effect (P > 0.1) in the concentrations used in this study. Increasing concentration of sodium chloride, sodium nitrite, sodium acetate, potassium lactate and calcium propionate in meat reduced bacterial growth rate while increasing pH in meat increased the growth rate of L. monocytogenes. The current mathematical equation will be an important tool in order to reduce the required number of challenge studies performed in order to ensure a safe food product. PMID- 26678139 TI - Microbial community assessment of mealworm larvae (Tenebrio molitor) and grasshoppers (Locusta migratoria migratorioides) sold for human consumption. AB - In Western countries, the popularity of edible insects as an alternative animal protein source is increasing. Nevertheless, there is a lack of profound insight into the microbial safety and shelf life of living insects sold for human consumption. The purpose of this study was to characterise the microflora of fresh edible mealworm larvae and grasshoppers in a quantitative and qualitative way. Therefore, culture-dependent analyses (the total viable aerobic count, Enterobacteriaceae, lactic acid bacteria, yeasts and moulds, and bacterial endospores) and next-generation sequencing (454amplicon pyrosequencing) were performed. High microbial counts were obtained for both insect species. Different insect batches resulted in quite similar microbial numbers, except for bacterial endospores. However, the bacterial community composition differed between both insect species. The most abundant operational taxonomic unit in mealworm larvae was Propionibacterium. Also members of the genera Haemophilus, Staphylococcus and Clostridium were found. Grasshoppers were mainly dominated by Weissella, Lactococcus and Yersinia/Rahnella. Overall, a variety of potential spoilage bacteria and food pathogens were characterised. The results of this study suggest that a processing step with a microbiocidal effect is required to avoid or minimize risks involved with the consumption of edible insects. PMID- 26678140 TI - Effect of yeast strain and some nutritional factors on tannin composition and potential astringency of model wines. AB - Nine Saccharomyces cerevisiae cultures, isolated from different sources, were tested for their ability to reduce tannins reactive towards salivary proteins, and potentially responsible for wine astringency. Strains were preliminary genetically characterized and evaluated for physiological features of technological interest. Laboratory-scale fermentations were performed in three synthetic media: CT) containing enological grape tannin; CTP) CT supplemented with organic nitrogen sources; CTPV) CTP supplemented with vitamins. Adsorption of total tannins, tannins reactive towards salivary proteins, yellow pigments, phenolics having antioxidant activity, and total phenols, characterizing the enological tannin, was determined by spectrophotometric methods after fermentation. The presence of vitamins and peptones in musts greatly influenced the adsorption of tannins reactive towards salivary proteins (4.24 g/L gallic acid equivalent), thus promoting the reduction of the potential astringency of model wines. With reference to the different phenolic classes, yeast strains showed different adsorption abilities. From a technological point of view, the yeast choice proved to be crucial in determining changes in gustative and mouthfeel profile of red wines and may assist winemakers to modulate colour and astringency of wine. PMID- 26678141 TI - The challenge of enumerating Listeria monocytogenes in food. AB - Listeria monocytogenes is recognised as a serious foodborne pathogen in humans. However, food products are usually contaminated at low levels (i.e. <100 CFU/g) and there is still no adequate enumeration method for testing food. Much research has been carried out to improve Listeria enumeration methods, leading to several proposed alternative methods such as the most probable number technique, molecular-based methods and bacterial cell concentration techniques. Here, we catalogue the current knowledge concerning L. monocytogenes enumeration, with a particular focus on the problem of enumerating low level contamination. PMID- 26678142 TI - The effects of citrus extract (Citrox(c)) on the naturally occurring microflora and inoculated pathogens, Bacillus cereus and Salmonella enterica, in a model food system and the traditional Greek yogurt-based salad Tzatziki. AB - The antimicrobial effect of citrus extract (at 1 mL/kg [TC1] and 2 mL/kg [TC2]) on the naturally occurring microflora and inoculated pathogens (Bacillus cereus and Salmonella enterica, at ca. 6 log cfu/g) in the traditional Greek yogurt based salad Tzatziki during storage under vacuum at 4 or 10 degrees C was examined. We also examined the effect of citrus extract (Citrox((c))) against the two aforementioned pathogens in tryptic soy broth (TSB). Of the two treatments, TC2 yielded the lowest yeast counts, irrespective of temperature, resulting in approximately 2 (4 degrees C) and 3 (10 degrees C) log reductions on the final day of storage (70 and 30 days, respectively). Although panelists preferred the TC1-treated salad, the TC2-treated product was sensorily acceptable. Therefore, at the concentrations used, Citrox had no negative sensorial effect on the Tzatziki. During storage, the Bacillus populations in the Citrox-treated Tzatziki samples progressively decreased, showing major declines from days 12 and 28 (at 10 and 4 degrees C, respectively). Citrox, especially at 2 mL/kg, had a significant effect on the survival of B. cereus. S. enterica showed major declines in all untreated Tzatziki samples from day 0-70 (4 degrees C) and from day 0-30 (10 degrees C), with averages of 2.5 and 2.8 log cfu/g, respectively. The results indicate that Citrox (at 1 and 2 mL/kg) is effective, from a safety standpoint, for reducing Bacillus and Salmonella spp. in Tzatziki. In addition, 2% citrus extract also showed a higher inhibitory effect against B. cereus and S. enterica grown in TSB than 1% citrus extract. PMID- 26678143 TI - Antimicrobial resistance and virulence genes in enterococci from wild game meat in Spain. AB - A total of 55 enterococci (45 Enterococcus faecium, 7 Enterococcus faecalis, and three Enterococcus durans) isolated from the meat of wild game animals (roe deer, boar, rabbit, pheasant, and pigeon) in North-Western Spain were tested for susceptibility to 14 antimicrobials by the disc diffusion method. All strains showed a multi-resistant phenotype (resistance to between three and 10 antimicrobials). The strains exhibited high percentages of resistance to erythromycin (89.1%), tetracycline (67.3%), ciprofloxacin (92.7%), nitrofurantoin (67.3%), and quinupristin-dalfopristin (81.8%). The lowest values (9.1%) were observed for high-level resistance to gentamicin, kanamycin, and streptomycin. The average number of resistances per strain was 5.8 for E. faecium isolates, 7.9 for E. faecalis, and 5.7 for E. durans. Genes encoding antimicrobial resistance and virulence were studied by polymerase chain reaction. A total of 15 (57.7%) of the 26 vancomycin-resistant isolates harboured the vanA gene. Other resistance genes detected included vanB, erm(B) and/or erm(C), tet(L) and/or tet(M), acc(6') aph(2"), and aph(3')-IIIa in strains resistant to vancomycin, erythromycin, tetracycline, gentamicin, and kanamycin, respectively. Specific genes of the Tn5397 transposon were detected in 54.8% of the tet(M)-positive enterococci. Nine virulence factors (gelE, agg, ace, cpd, frs, esp, hyl, efaAfs and efaAfm) were studied. All virulence genes, with the exception of the frs gene, were found to be present in the enterococcal isolates. At least one virulence gene was detected in 20.0% of E. faecium, 71.4% of E. faecalis and 33.3% of E. durans isolates, with ace and cpd being the most frequently detected genes (6 isolates each). This suggests that wild game meat might play a role in the spreading through the food chain of enterococci with antimicrobial resistance and virulence determinants to humans. PMID- 26678144 TI - Inactivation kinetics of Listeria monocytogenes and Salmonella enterica serovar Typhimurium on fresh-cut bell pepper treated with slightly acidic electrolyzed water combined with ultrasound and mild heat. AB - The goal of this study was to enhance the antimicrobial effect of slightly acidic electrolyzed water (SAEW) through addition of synergistic treatment with ultrasound (US) and mild heat treatment in order to improve the microbial safety of fresh-cut bell pepper. To evaluate the synergistic effects, the Weibull model was used to mathematically measure the effectiveness of the individual and combined treatments against Listeria monocytogenes and Salmonella Typhimurium on the pepper. The combined treatment (SAEW+US+60 degrees C) resulted in the TR values of 0.04 and 0.09 min for L. monocytogenes and S. Typhimurium, respectively, as consequence of the minimum value. Subsequently, texture analysis was carried out to test the potential effect on quality of the samples due to the involved mild heat and ultrasound treatment. When compared to the control, there was no significant change (p >= 0.05) in the texture (color and hardness) of the samples that were treated by 1 min of the combined treatment (SAEW+US+60 degrees C) during storage at 4 degrees C for 7 days. This combined treatment achieved approximately 3.0 log CFU/g reduction in the two pathogens. The results demonstrate that the involved hurdle factors which are ultrasound and mild heat achieved the synergistic effect of SAEW against the two pathogens. According to the results of texture analysis, 1 min of SAEW+US+60 degrees C is the optimal condition due to without negative influence on the quality of the samples during the storage. The optimal condition shows the enhanced antimicrobial effect of SAEW and enables to improve microbial safety of fresh bell pepper in food industry as a consequence of hurdle approach. PMID- 26678145 TI - Characterization of yeasts isolated from artisanal short-ripened cows' cheeses produced in Galicia (NW Spain). AB - A total of 143 presumptive yeast isolates were obtained from the predominant microflora of 21 short-ripened starter-free raw cow's milk cheeses made in Galicia (NW Spain), and the following 68 isolates were identified by both genotyping and sequencing methods: Yarrowia lipolytica (21 isolates), Kluyveromyces lactis (18), Debaryomyces hansenii (11), Pichia guilliermondii (11), Pichia fermentans (4) and Saccharomyces cerevisiae (3). Of these, Y. lipolytica and K. lactis displayed the strongest extracellular proteolytic activity on skim milk agar, and none of the D. hansenii isolates showed any activity on this medium. Y. lipolytica also displayed the highest lipolytic activity on Tween 80 and on tributyrin. This species, which was characterized by production of butanoic acid, free fatty acid esters and sulfur compounds in pasteurized whole milk, was responsible for rancid and cheesy flavors. K. lactis mainly produced acetaldehyde, ethanol, branched chain aldehydes and alcohols, and acetic acid esters, which were responsible for alcoholic, fruity and acetic notes. The volatile profiles of D. hansenii were rather limited and characterized by high levels of methyl ketones. Most of the yeast isolates were described as tryptamine producers, although low concentrations of histamine were produced by five Y. lipolytica and two P. fermentans isolates. We conclude that selected Y. lipolytica strains could be used as adjunct cultures in the manufacture of Arzua Ulloa and Tetilla cheeses, and selected K. lactis strains could be used as co starters in the manufacture of acid curd Cebreiro cheese, thus contributing to the sensory quality and typicality of the cheeses. PMID- 26678146 TI - Volatile chemical spoilage indexes of raw Atlantic salmon (Salmo salar) stored under aerobic condition in relation to microbiological and sensory shelf lives. AB - The purpose of this investigation was to identify and quantify the volatile chemical spoilage indexes (CSIs) for raw Atlantic salmon (Salmo salar) fillets stored under aerobic storage conditions at 4, 10 and 21 degrees C in relation to microbial and sensory shelf lives. The volatile organic compounds (VOCs) were analyzed with SPME-GC-MS technique. Through multivariate chemometric method, hierarchical cluster analysis (HCA) and Pearson's correlations, the CSIs: trimethylamine (TMA), ethanol (EtOH), 3-methyl-1-butanol (3Met-1But), acetoin and acetic acid (C2) were selected from the group of 28 detected VOCs. At the moment of microbiological shelf life established at total viable count (TVC) of 7.0 log CFU/g, the CSIs achieved levels of 11.5, 38.3, 0.3, 24.0 and 90.7 MUg/g of salmon for TMA, EtOH, 3M-1But, acetoin and C2, respectively. Pseudomonas spp. was found as major specific spoilage organism (SSOs), suitable for shelf life prediction using modified Gompertz model at the cut-off level of 6.5 log CFU/g. H2S producing bacteria and Brochothrix thermosphacta were considered as important spoilage microorganisms; however, they were not suitable for shelf life estimation. Partial least square (PLS) regression revealed possible associations between microorganisms and synthetized VOCs, showing correlations between Pseudomonas spp. and 3Met-1But and aldehydes synthesis, lactic acid bacteria were linked with EtOH, C2 and esters, and B. thermosphacta with acetoin formation. PMID- 26678147 TI - Optimizing biologic treatment in IBD: objective measures, but when, how and how often? AB - BACKGROUND: The advent of biologic agents for the treatment of inflammatory bowel disease (IBD) was accompanied in parallel with emerging understanding of persisting underlying inflammation and ensuing bowel damage that can occur even in patients with seeming clinical remission. This lead to the concepts of mucosal healing and deep remission gaining acceptance as the more desired goals for therapy within an ambitious disease-control therapeutic approach, namely, treat to-target strategy. However, how to practically monitor IBD patients, which objective measures to follow, at what time-points and whether to act upon results in asymptomatic patients are all questions that remain disputed. METHODS AND RESULT: In this concise review we aim to provide an overview of objective measures for monitoring of IBD patients, focusing on the challenging group of patients treated by infliximab, adalimumab, vedolizumab and other biologics. These objective measures are discussed in the context of the different common clinical scenarios wherein the clinician may contemplate their use. Specifically, we will delineate the role of objective parameters to be monitored during induction phase of treatment, during maintenance therapy, at loss of response and after elective cessation of therapy in patients in remission. CONCLUSION: Coupled with the non-negligible costs of therapy, and the over-all worse prognosis of moderate-severe patients who are the usual recipients of biologic therapies, this challenging patients seem to be the first candidates for this more proactive strategy combining inflammatory and pharmacokinetic monitoring of objective inflammatory and pharmacokinetic measures. More data is still desirable to better define the exact parameters to be followed and their optimal thresholds, and to delineate the optimal cost-effective interventions for these patients. PMID- 26678148 TI - An embryological perspective on the early arthropod fossil record. AB - BACKGROUND: Our understanding of the early evolution of the arthropod body plan has recently improved significantly through advances in phylogeny and developmental biology and through new interpretations of the fossil record. However, there has been limited effort to synthesize data from these different sources. Bringing an embryological perspective into the fossil record is a useful way to integrate knowledge from different disciplines into a single coherent view of arthropod evolution. RESULTS: I have used current knowledge on the development of extant arthropods, together with published descriptions of fossils, to reconstruct the germband stages of a series of key taxa leading from the arthropod lower stem group to crown group taxa. These reconstruction highlight the main evolutionary transitions that have occurred during early arthropod evolution, provide new insights into the types of mechanisms that could have been active and suggest new questions and research directions. CONCLUSIONS: The reconstructions suggest several novel homology hypotheses - e.g. the lower stem group head shield and head capsules in the crown group are all hypothesized to derive from the embryonic head lobes. The homology of anterior segments in different groups is resolved consistently. The transition between "lower-stem" and "upper-stem" arthropods is highlighted as a major transition with a concentration of novelties and innovations, suggesting a gap in the fossil record. A close relationship between chelicerates and megacheirans is supported by the embryonic reconstructions, and I suggest that the depth of the mandibulate chelicerate split should be reexamined. PMID- 26678149 TI - Prevalence of suspected developmental delays in early infancy: results from a regional population-based longitudinal study. AB - BACKGROUND: Prevalence estimates on suspected developmental delays (SDD) in young infants are scarce and a necessary first step for planning an early intervention. We investigated the prevalence of SDD at 4, 6 and 12 months, in addition to associations of SDD with gender, prematurity and maternal education. METHODS: This study is based on a Norwegian longitudinal sample of 1555 infants and their parents attending well-baby clinics for regular health check-ups. Moreover, parents completed the Norwegian translation of the Ages and Stages Questionnaires (ASQ) prior to the check-up, with a corrected gestational age being used to determine the time of administration for preterm infants. Scores <= the established cut-offs in one or more of the five development areas: communication, gross motor, fine motor, problem solving and personal-social, which defined SDD for an infant were reported. Chi-square tests were performed for associations between the selected factors and SDD. RESULTS: According to established Norwegian cut-off points, the overall prevalence of SDD in one or more areas was 7.0 % (10.3 % US cut-off) at 4 months, 5.7 % (12.3 % US cut-off) at 6 months and 6.1 % (10.3 % US cut-off) at 12 months. The highest prevalence of SDD was in the gross motor area at all three time points. A gestational age of < 37 weeks revealed a significant association with the communication SDD at 4 months, and with the fine motor and personal social SDD at 6 months. Gender was significantly associated with the fine motor and problem solving SDD at 4 months and personal- social SDD at 6 months: as more boys than girls were delayed. No significant associations were found between maternal education and the five developmental areas of the ASQ. CONCLUSION: Our findings indicate prevalence rates of SDD between 5.7 and 7.0 % in Norwegian infants between 4 and 12 months of age based on the Norwegian ASQ cut-off points (10.3-12.3 %, US cut-off points). During the first year of life, delay is most frequent within the gross motor area. Special attention should be paid to infants born prematurely, as well as to boys. Separate norms for boys and girls should be considered for the ASQ. PMID- 26678150 TI - Atypical pityriasis rosea presenting with a herald patch lesion on the healed site of herpes zoster: Wolf's isotopic response. PMID- 26678151 TI - Is manual palpation of the lung necessary in patients undergoing pulmonary metastasectomy? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether manual palpation of the lung is necessary in patients undergoing pulmonary metastasectomy. In total, 56 articles were found using the described search strategy. After screening these articles and their references, 18 publications represented the best evidence to answer the clinical question. No randomized controlled trial addressing the three-part question was available. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers were tabulated. The studies reported on 1472 patients with different primary cancers. The patients underwent more than 1630 pulmonary metastasectomies between 1990 and 2014 after the treatment of primary cancer. Almost three quarters of patients underwent open procedures like thoracotomy or sternotomy. Most frequently, helical CT with a slice thickness ranging between 1 and 10 mm was used for preoperative imaging. The sensitivity in detecting pulmonary nodules ranged from 34 to 97%. The corresponding sensitivity rates for PET-CT were 66-67.5 and 75% for high-resolution CT. The positive predictive value for lesions detected by helical CT varied from 47 to 96%. Helical CT reached a specificity between 54 and 93% in detecting pulmonary nodules. The surgeons identified more nodules by meticulous palpation than helical CT. It is noteworthy that up to 48.5% of these palpated nodules were benign lesions (false-positive). Patients with smaller imaged nodules, multiple imaged nodules or primary mesenchymal tumour are more likely to have occult pulmonary nodules. We conclude that not all palpable pulmonary nodules can be imaged preoperatively. Thoracotomy allows the manual palpation of the ipsilateral hemithorax and might be superior to video-assisted thoracic surgery regarding radical resection. However, not all palpable nodules are malignant, and the impact of non-resected pulmonary metastases on patient survival is not clearly evaluated. PMID- 26678153 TI - [Simulation-based medical education: What are the challenges?]. PMID- 26678152 TI - Optimal timing for early surgery in infective endocarditis: a meta-analysis. AB - To systematically review early surgery and the optimal timing of surgery in patients with infective endocarditis (IE), a search for foreign and domestic articles on cohort studies about the association between early surgery and infective endocarditis published from inception to January 2015 was conducted in the PubMed, EMBASE, Chinese Biomedical Literature (CBM), Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases. The studies were screened according to the inclusion and exclusion criteria, the data were extracted and the quality of the method of the included studies was assessed. Then, the meta analysis was performed using the Stata 12.0 software. Sixteen cohort studies, including 8141 participants were finally included. The results of the meta analysis revealed that, compared with non-early surgery, early surgery in IE lowers the incidence of in-hospital mortality [odds ratio (OR) = 0.57, 95% confidence interval (CI) (0.42, 0.77); P = 0.000, I(2) = 73.1%] and long-term mortality [OR = 0.57, 95% CI (0.43, 0.77); P = 0.001, I(2) = 67.4%]. Further, performing operation within 2 weeks had a more favourable effect on long-term mortality [OR = 0.63, 95% CI (0.41, 0.97); P = 0.192, I(2) = 39.4%] than non early surgery. In different kinds of IE, we found that early surgery for native valve endocarditis (NVE) had a lower in-hospital [OR = 0.46, 95% CI (0.31, 0.69); P = 0.001, I(2) = 73.0%] and long-term [OR = 0.57, 95% CI (0.40, 0.81); P = 0.001, I(2) = 68.9%] mortality than the non-early surgery group. However, for prosthetic valve endocarditis (PVE), in-hospital mortality did not differ significantly [OR = 0.83, 95% CI (0.65, 1.06); P = 0.413, I(2) = 0.0%] between early and non-early surgery. We concluded that early surgery was associated with lower in-hospital and long-term mortality compared with non-early surgical treatment for IE, especially in NVE. However, the optimal timing of surgery remains unclear. Additional larger prospective clinical trials will be required to clarify the optimal timing for surgical intervention and determine its efficacy in PVE. PMID- 26678154 TI - Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules. AB - Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08 0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3 diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (PhiDelta) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT. PMID- 26678156 TI - Incidence and Predictors of In-stent Re-Stenosis in the Superficial Femoral Artery: Evaluation of Long-Term Outcomes by Color Duplex Ultrasound. AB - This study aimed to investigate the incidence and predictors of in-stent re stenosis (ISR) for nitinol stents in the superficial femoral artery (SFA) by color duplex ultrasound (CDU). In total, 235 patients undergoing SFA stenting were included in the present study. The cumulative ISR rates at 3, 6, 12, 24 and 36 mo post-procedure were 5.4%, 24.0%, 49.0%, 61.5% and 71.5%, respectively. The markedly low peak systolic velocity of the popliteal artery (PSV2) post-operation was inversely correlated with the ISR. The threshold for >=50% re-stenosis was PSV2 <= 63 cm/s with 86.6% sensitivity and 90.5% specificity. With regard to re occlusion, the PSV2 was <=40 cm/s with 98.1% sensitivity and 93.4% specificity. Cox regression analysis indicated that the cumulative stent length, diabetes, and pre-stent stenosis level were independent risk factors of ISR. In conclusion, the ISR incidence after SFA stenting is relatively high and CDU follow-up is a feasible method for evaluating ISR. PMID- 26678155 TI - Molecular Acoustic Angiography: A New Technique for High-resolution Superharmonic Ultrasound Molecular Imaging. AB - Ultrasound molecular imaging utilizes targeted microbubbles to bind to vascular targets such as integrins, selectins and other extracellular binding domains. After binding, these microbubbles are typically imaged using low pressures and multi-pulse imaging sequences. In this article, we present an alternative approach for molecular imaging using ultrasound that relies on superharmonic signals produced by microbubble contrast agents. Bound bubbles were insonified near resonance using a low frequency (4 MHz) element and superharmonic echoes were received at high frequencies (25-30 MHz). Although this approach was observed to produce declining image intensity during repeated imaging in both in vitro and in vivo experiments because of bubble destruction, the feasibility of superharmonic molecular imaging was demonstrated for transmit pressures, which are sufficiently high to induce shell disruption in bound microbubbles. This approach was validated using microbubbles targeted to the alphavbeta3 integrin in a rat fibrosarcoma model (n = 5) and combined with superharmonic images of free microbubbles to produce high-contrast, high-resolution 3-D volumes of both microvascular anatomy and molecular targeting. Image intensity over repeated scans and the effect of microbubble diameter were also assessed in vivo, indicating that larger microbubbles yield increased persistence in image intensity. Using ultrasound-based acoustic angiography images rather than conventional B-mode ultrasound to provide the underlying anatomic information facilitates anatomic localization of molecular markers. Quantitative analysis of relationships between microvasculature and targeting information indicated that most targeting occurred within 50 MUm of a resolvable vessel (>100 MUm diameter). The combined information provided by these scans may present new opportunities for analyzing relationships between microvascular anatomy and vascular targets, subject only to limitations of the current mechanically scanned system and microbubble persistence to repeated imaging at moderate mechanical indices. PMID- 26678157 TI - Physical exercise mitigates doxorubicin-induced brain cortex and cerebellum mitochondrial alterations and cellular quality control signaling. AB - Doxorubicin (DOX) is a highly effective anti-neoplastic agent, whose clinical use is limited by a dose-dependent mitochondrial toxicity in non-target tissues, including the brain. Here we analyzed the effects of distinct exercise modalities (12-week endurance treadmill-TM or voluntary free-wheel activity-FW) performed before and during sub-chronic DOX treatment on brain cortex and cerebellum mitochondrial bioenergetics, oxidative stress, permeability transition pore (mPTP), and proteins involved in mitochondrial biogenesis, apoptosis and auto(mito)phagy. Male Sprague-Dawley rats were divided into saline-sedentary (SAL+SED), DOX-sedentary (DOX+SED; 7-week DOX (2 mg . kg(-1)per week)), DOX+TM and DOX+FW. Animal behavior and post-sacrifice mitochondrial function were assessed. Oxidative phosphorylation (OXPHOS) subunits, oxidative stress markers or related proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn SOD), as well as proteins involved in mitochondrial biogenesis (PGC1alpha and TFAM) were evaluated. Apoptotic signaling was followed through caspases 3, 8 and 9-like activities, Bax, Bcl2, CypD, ANT and cofilin expression. Mitochondrial dynamics (Mfn1, Mfn2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin and p62)-related proteins were measured by semi-quantitative Western blotting. DOX impaired behavioral performance, mitochondrial function, including lower resistance to mPTP and increased apoptotic signaling, decreased the content in OXPHOS complex subunits and increased oxidative stress in brain cortex and cerebellum. Molecular markers of mitochondrial biogenesis, dynamics and autophagy were also altered by DOX treatment in both brain subareas. Generally, TM and FW were able to mitigate DOX-related impairments in brain cortex and cerebellum mitochondrial activity, mPTP and apoptotic signaling. We conclude that the alterations in mitochondrial biogenesis, dynamics and autophagy markers induced by exercise performed before and during treatment may contribute to the observed protective brain cortex and cerebellum mitochondrial phenotype, which is more resistant to oxidative damage and apoptotic signaling in sub-chronically DOX treated animals. PMID- 26678159 TI - Leukoreduction system chambers provide a valuable source of functional monocytes for the monocyte activation test by comparison with internationally validated methods. AB - Despite being added to the European Pharmacopoeia in 2010 and strongly supported by the European directive enforcing the "3R's" - Replace, Reduce and Refine, uptake of the monocyte activation test (MAT) in preference over the rabbit pyrogen test for the detection of pyrogens has been limited. This has been attributed to the difficulty in sourcing human monocytes due to the necessity of phlebotomy. This study has attempted to address this issue by evaluating cryopreserved peripheral blood mononuclear cells (PBMCs) isolated from leukoreduction system chambers (LRSCs), a readily available by-product of platelet apheresis, as a source of monocytes for the MAT. Validation was performed by direct comparison with the two most commonly employed primary monocyte sources: fresh whole blood (WB) and PBMCs from fresh blood, assessing their ability to detect a panel of toll-like receptor (TLR) ligands including Pam3CSK4, Lipoteichoic acid, Peptidoglycan, Poly(I:C) and Flagellin, as well as two different endotoxin sources, with IL-1beta and IL-6 as the readouts. All three cell sources were able to detect the pyrogens included in the study with comparable sensitivities, with the exception of TLR3 ligand Poly(I:C). The WB assay produced quantifiable, but significantly lower cytokine levels with every pyrogen tested than either of the PBMCs sources used. LRSCs provided an ample and convenient source of PBMCs which were successfully cryopreserved, providing cell banks for each donor, shown to maintain stability for at least a year. The use of cryopreserved PBMCs reduced the time and effort required to set up an assay, and the availability of single donor cell banks will allow investigations into assay variables in the absence of inter-donor variability. Significantly higher sensitivity to Pam3CSK4 was observed with a proportion of donors. This was found to correlate to single nucleotide polymorphisms rs4833095 and rs5743618 of TLR1. This evidence, along with the wide range of other SNPs identified in TLR regions without known biological function, supports caution in the practice of pooling donor cells in order to overcome donor-to-donor variation. PMID- 26678158 TI - Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress. AB - The 4977 bp common deletion is one of the most frequently observed mitochondrial DNA (mtDNA) mutations in human tissues and has been implicated in various human cancer types. It is generally believed that continuous generation of intracellular reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS) is a major underlying mechanism for generation of such mtDNA deletions while antioxidant systems, including Manganese superoxide dismutase (MnSOD), mitigating the deleterious effects of ROS. However, the clinical significance of this common deletion remains to be explored. A comprehensive investigation on occurrence and accumulation of the common deletion and mtDNA copy number was carried out in breast carcinoma (BC) patients, benign breast disease (BBD) patients and age-matched healthy donors in our study. Meanwhile, the representative oxidative (ROS production, mtDNA and lipid oxidative damage) and anti-oxidative features (MnSOD expression level and variation) in blood samples from these groups were also analyzed. We found that the mtDNA common deletion is much more likely to be detected in BC patients at relatively high levels while the mtDNA content is lower. This alteration has been associated with a higher MnSOD level and higher oxidative damages in both BC and BBD patients. Our results indicate that the mtDNA common deletion in blood may serve a biomarker for the breast cancer. PMID- 26678160 TI - A small volume technique to examine and compare alveolar macrophage phagocytosis of apoptotic cells and non typeable Haemophilus influenzae (NTHi). AB - A defective ability of alveolar macrophages to phagocytose both apoptotic airway epithelial cells and bacteria in chronic lung diseases potentially associated with inflammation and bacterial colonisation of the lower airways, often with non typeable Haemophilus influenzae (NTHi), has been shown. We routinely assess phagocytosis in the airway of children: however, the small volume of BAL obtained usually precludes the investigation of phagocytosis of both (potentially equally relevant) apoptotic cells and NTHi. METHODS: We established a 'one-tube, dual target' flow-cytometric assay for investigating alveolar macrophage phagocytosis of both apoptotic cells and NTHi. The effect of bacterial presence on phagocytosis of apoptotic cells was assessed by comparing results using this technique to standard 'two tube, single target' methods. The comparative ability of alveolar macrophages to phagocytose NTHi or apoptotic cells was assessed in 10/group of healthy adult controls and patients with COPD, 12 children with bronchiectasis, and 10 children controls. We then assessed the influence of increasing concentrations of NTHi targets on the ability of THP-1 macrophages to simultaneously phagocytose apoptotic cells. RESULTS: Alveolar macrophages phagocytosed NTHi more avidly than apoptotic cells (mean +/- SEM: apoptotic cells 15.4% +/- 0.5 vs. NTHi 17.2% +/- 0.7, p<0.05). The presence of NTHi targets (ratio of 1:100 macrophage: NTHi; 2 * 1 0(7) CFU routinely applied in our assay) had no effect on the ability of macrophages to simultaneously phagocytose apoptotic cells. However, when bacterial numbers were increased (up to 4-fold) there was a small but significant suppressive effect on the ability of macrophages to phagocytose apoptotic cells. CONCLUSIONS: We describe a small volume 'one tube, dual target' technique to measure phagocytosis of apoptotic cells and NTHi. We show that alveolar macrophages phagocytose NTHi more avidly than apoptotic cells, and that an increased presence of NTHi in the airway may reduce the ability of alveolar macrophages to phagocytose apoptotic cells. PMID- 26678161 TI - High level expression and purification of active recombinant human interleukin-15 in Pichia pastoris. AB - Interleukin-15 (IL-15) is a pleiotropic cytokine and a member of the four alpha helix bundle family of cytokines which include IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. IL-15 exhibits a broad biological activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. In this study, a DNA fragment containing the mature human IL-15 sequence was cloned into pPICZaA vector, generating a fusion protein with the alpha factor signal sequence in the N-terminus and 6*His as well as c-Myc tags in the C-terminus. The resulting plasmid was integrated into the genome of Pichia pastoris strain X-33. Recombinant yeast transformants with high-level recombinant human IL-15 (rhIL-15) production were identified, which secrete as much as 75 mg/L rhIL-15 after 3 days of induction by methanol. The rhIL-15 was purified by Ni(+)-NTA affinity chromatography, followed by DEAE anion exchange, yielding over 95% highly purified rhIL-15. Mass spectrometry and MALDI-TOF-TOF analysis showed the purified rhIL-15 had larger molecular weights than expected, due to different degrees of N-linked glycosylation. The biological activity of the rhIL-15 proteins was measured by its ability to enhance cellular proliferation of CTLL-2 and NK cells. The results demonstrate that the experimental procedure we have reported here can produce a large amount of active recombinant human IL-15 from P. pastoris. PMID- 26678163 TI - Reframing convenience food. AB - This paper provides a critical review of recent research on the consumption of 'convenience' food, highlighting the contested nature of the term and exploring its implications for public health and environmental sustainability. It distinguishes between convenience food in general and particular types of convenience food, such as ready-meals, tracing the structure and growth of the market for such foods with a particular emphasis on the UK which currently has the highest rate of ready-meal consumption in Europe. Having established the definitional complexities of the term, the paper presents the evidence from a systematic review of the literature, highlighting the significance of convenience food in time-saving and time-shifting, the importance of recent changes in domestic labour and family life, and the way the consumption of convenience food is frequently moralized. The paper shows how current debates about convenience food are part of a longer discursive history about food, health and nutrition. It discusses current levels of public understanding about the links between convenience food, environmental sustainability and food waste. The paper concludes by making a case for understanding the consumption of convenience food in terms of everyday social practices, emphasising its habitual and routine character. PMID- 26678162 TI - SLE-key((r)) rule-out serologic test for excluding the diagnosis of systemic lupus erythematosus: Developing the ImmunArray iCHIP((r)). AB - We describe here the development, verification and validation of the SLE-key((r)) rule-out test for a definitive rule-out of a diagnosis of systemic lupus erythematosus (SLE). The test uses the proprietary iCHIP((r)) micro-array technology platform (Fattal et al., 2010) to identify discriminating patterns of circulating autoantibodies among SLE patients compared with self-declared healthy individuals. Given the challenges associated with the diagnosis of SLE and the healthcare costs of delayed diagnosis and misdiagnosis, a definitive rule-out test can provide significant clinical benefits to patients and potentially major cost savings to healthcare systems. PMID- 26678164 TI - [Cornual pregnancy: Management and subsequent fertility]. AB - OBJECTIVE: Cornual pregnancy is a rare entity, representing 2% of ectopic pregnancies. Its management is poorly codified and often guided by the clinical situation. The aim of our study was to describe the management of cornual pregnancies, subsequent fertility, and obstetric outcomes according to the management. METHODS: Observational retrospective unicentric study. Nineteen patients hospitalized for cornual pregnancy between 2006 and 2015 were included. The data was collected with medical records and a phone standardized questionnaire. Patients were managed according to hemodynamic status by either systemic or local methotrexate injection or surgical corneal resection. RESULTS: Among the 19 patients, 32% (6) were treated by systemic injection (one failure treated by surgical treatment) and 68% (13) underwent surgical treatment by cornual resection. The median HCG rate decrease was 33 days (16-62). Among the twelve patients with a desire for a new pregnancy, 7 (58%) became pregnant without assisted reproductive technology (2 following medical treatment and 5 following surgical resection). Histological analysis of uterine horn showed proximal fallopian tube lesions in 76.9% of case (chronic salpingitis, endosalpingiosis and adenomyosis). CONCLUSION: Cornual pregnancies are at high risk of hemorrhagic rupture. Ectopic recidive may occur. Fertility and obstetrical outcomes following cornual pregnancy are not affected whatever the initial treatment. Other studies are needed to aid clinical management according to HCG level and ultrasound features. PMID- 26678165 TI - [Tacrolimus-induced gynecomastia in a patient with polymyositis]. PMID- 26678166 TI - [Usefulness of preoperative echocardiogram in patients with morbid obesity]. PMID- 26678167 TI - [Herpes simplex virus encephalitis during pregnancy: Maternal and neonatal outcomes]. PMID- 26678168 TI - Sexual selection and population divergence I: The influence of socially flexible cuticular hydrocarbon expression in male field crickets (Teleogryllus oceanicus). AB - Debates about how coevolution of sexual traits and preferences might promote evolutionary diversification have permeated speciation research for over a century. Recent work demonstrates that the expression of such traits can be sensitive to variation in the social environment. Here, we examined social flexibility in a sexually selected male trait-cuticular hydrocarbon (CHC) profiles-in the field cricket Teleogryllus oceanicus and tested whether population genetic divergence predicts the extent or direction of social flexibility in allopatric populations. We manipulated male crickets' social environments during rearing and then characterized CHC profiles. CHC signatures varied considerably across populations and also in response to the social environment, but our prediction that increased social flexibility would be selected in more recently founded populations exposed to fluctuating demographic environments was unsupported. Furthermore, models examining the influence of drift and selection failed to support a role of sexual selection in driving population divergence in CHC profiles. Variation in social environments might alter the dynamics of sexual selection, but our results align with theoretical predictions that the role social flexibility plays in modulating evolutionary divergence depends critically on whether responses to variation in the social environment are homogeneous across populations, or whether gene by social environment interactions occur. PMID- 26678169 TI - "I sit to sleep"-Spirometry as a clue to diagnosis. AB - A 15-year-old patient presented with a 4-month history of choking while sleeping that necessitated sleeping in a sitting position. Flow-volume curve demonstrating fixed upper airway obstruction led to further workup and to the diagnosis of childhood achalasia as a cause of unusual symptoms and fixed upper airway obstruction. Pediatr Pulmonol. 2016;51:E13-E15. (c) 2015 Wiley Periodicals, Inc. PMID- 26678170 TI - Evaluation of the clinical relevance and limitations of current pre-clinical models of peripheral artery disease. AB - Peripheral arterial disease (PAD) usually results from atherosclerosis and associated thrombosis and limits blood supply to the lower limbs. Common presenting symptoms include intermittent claudication (IC), rest pain and tissue loss. When limb viability is threatened, known as critical limb ischaemia (CLI), surgical and endovascular interventions are frequently undertaken; however, these are not always successful and ultimately major amputation may be required. There is significant interest in developing new therapeutic approaches to manage PAD which can be applied to patients unlikely to benefit from interventional approaches. Many of the therapeutic agents successful in inducing angiogenesis and arteriogenesis in pre-clinical animal models of PAD have failed to have efficacy in human randomized control trials. One possible reason for this inability to translate findings to patients could be the type of pre-clinical animal models used. In the present review, we describe currently available pre clinical models of PAD and discuss the advantages and disadvantages of the available models. A detailed assessment of the currently available pre-clinical animal models shows major limitations such as variability in the surgical procedure used to induce limb ischaemia, variability in the strains of rodents used, lack of risk factors incorporated into the model and lack of standardized functional outcomes. The most commonly used outcome assessments in studies within pre-clinical models differ from those employed in clinical trials within PAD patients. Most current pre-clinical models are designed to produce acute ischaemia which leads to muscle necrosis and inflammation. Patients, however, most commonly present with chronic ischaemia suggesting that more representative models are needed to evaluate therapeutic modalities that can be potentially translated to clinical practice. PMID- 26678171 TI - Nox1 in cardiovascular diseases: regulation and pathophysiology. AB - Since its discovery in 1999, a number of studies have evaluated the role of Nox1 NADPH oxidase in the cardiovascular system. Nox1 is activated in vascular cells in response to several different agonists, with its activity regulated at the transcriptional level as well as by NADPH oxidase complex formation, protein stabilization and post-translational modification. Nox1 has been shown to decrease the bioavailability of nitric oxide, transactivate the epidermal growth factor receptor, induce pro-inflammatory signalling, and promote cell migration and proliferation. Enhanced expression and activity of Nox1 under pathologic conditions results in excessive production of reactive oxygen species and dysregulated cellular function. Indeed, studies using genetic models of Nox1 deficiency or overexpression have revealed roles for Nox1 in the pathogenesis of cardiovascular diseases ranging from atherosclerosis to hypertension, restenosis and ischaemia/reperfusion injury. These data suggest that Nox1 is a potential therapeutic target for vascular disease, and drug development efforts are ongoing to identify a specific bioavailable inhibitor of Nox1. PMID- 26678172 TI - Inhibition of carbonic anhydrase isoforms I, II, IV, VII and XII with carboxylates and sulfonamides incorporating phthalimide/phthalic anhydride scaffolds. AB - We report a panel of carboxylates and sulfonamides incorporating phthalic anhydride and phthalimide moieties in their structure and their interaction with the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). They were synthesized from substituted anthranilic acids and trimellitic anhydride chloride, followed by reaction with primary amines and were tested for the inhibition of five physiologically relevant CA isoforms, the human (h) hCA I, II, IV, VII and XII, some of which are involved in serious pathologies (CA II, IV and XII in glaucoma; CA VII in epilepsy; CA XII in some solid tumors). The carboxylic acids were generally poor inhibitors of isoforms hCA I, II and IV but were highly effective, low nanomolar inhibitors of hCA VII and XII. The sulfonamides inhibited all isoforms significantly, and some of them were sub-nanomolar hCA VII inhibitors, although their isoform selectivity was lower compared to the carboxylates. This study proves that carboxylic acids incorporating a phthalic anhydride/phthalimide based scaffold may lead to isoform-selective inhibitors by applying the tail approach, mostly used up until now for obtaining sulfonamide, sulfamide and sulfamate CA inhibitors. PMID- 26678174 TI - Human telomeric G-quadruplex DNA interactions of N-phenanthroline glycosylamine copper(II) complexes. AB - We report in this article the interactions of five N-(1,10-phenanthrolin-5-yl) beta-glycopyranosylamine copper(II) complexes with G-quadruplex DNA. Specifically, the interactions of these compounds with a human telomeric oligonucleotide have been assessed by fluorescence-based assays (FRET melting and G4-FID), circular dichroism and competitive equilibrium dialysis experiments. The metal complexes bind and stabilize G-quadruplex DNA structures with apparent association constants in the order of 10(4)-10(5)M(-1) and the affinity observed is dependent on the ionic conditions utilized and the specific nature of the carbohydrate moiety tethered to the 1,10-phenanthroline system. The compounds showed only a slight preference to bind G-quadruplex DNA over duplex DNA when the quadruplex DNA was folded in sodium ionic conditions. However, the binding affinity and selectivity, although modest, were notably increased when the G quadruplex DNA was folded in the presence of potassium metal ions. Moreover, the study points towards a significant contribution of groove and/or loop binding in the recognition mode of quadruplex structures by these non-classical quadruplex ligands. The results reported herein highlight the potential and the versatility of carbohydrate bis-phenanthroline metal-complex conjugates to recognize G quadruplex DNA structures. PMID- 26678173 TI - Serial incorporation of a monovalent GalNAc phosphoramidite unit into hepatocyte targeting antisense oligonucleotides. AB - The targeting of abundant hepatic asialoglycoprotein receptors (ASGPR) with trivalent N-acetylgalactosamine (GalNAc) is a reliable strategy for efficiently delivering antisense oligonucleotides (ASOs) to the liver. We here experimentally demonstrate the high systemic potential of the synthetically-accessible, phosphodiester-linked monovalent GalNAc unit when tethered to the 5'-terminus of well-characterised 2',4'-bridged nucleic acid (also known as locked nucleic acid) modified apolipoprotein B-targeting ASO via a bio-labile linker. Quantitative analysis of the hepatic disposition of the ASOs revealed that phosphodiester is preferable to phosphorothioate as an interunit linkage in terms of ASGPR binding of the GalNAc moiety, as well as the subcellular behavior of the ASO. The flexibility of this monomeric unit was demonstrated by attaching up to 5 GalNAc units in a serial manner and showing that knockdown activity improves as the number of GalNAc units increases. Our study suggests the structural requirements for efficient hepatocellular targeting using monovalent GalNAc and could contribute to a new molecular design for suitably modifying ASO. PMID- 26678175 TI - Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors. AB - Recently numerous non-fluoroquinolone-based bacterial type II topoisomerase inhibitors from both the GyrA and GyrB classes have been reported as antibacterial agents. Inhibitors of the GyrA class include aminopiperidine-based novel bacterial type II topoisomerase inhibitors (NBTIs). However, inhibition of the cardiac ion channel remains a serious liability for the aminopiperidine based NBTIs. In this paper we replaced central aminopiperidine linker with piperazine moiety and tested for its biological activity. We developed a series of twenty four compounds with a piperazine linker 1-(2-(piperazin-1-yl)ethyl)-1,5 naphthyridin-2(1H)-one, by following a multistep protocol. Among them compound 4 (2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)-N-(4-nitrophenyl)piperazine 1-carboxamide (11) was the most promising inhibitor with Mycobacterium tuberculosis (MTB) DNA gyrase enzyme supercoiling IC50 of 0.29+/-0.22MUM, with a good MTB MIC of 3.45MUM. These kind of compounds retains good potency and showed reduced cardiotoxicity compared to aminopiperidines. PMID- 26678176 TI - Determination of parthenolide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study. AB - A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination and pharmacokinetic investigation of parthenolide in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile containing 30ng/mL of pirfenidone (IS), and to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0min and the elution of parthenolide was at 1.33min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 249.2->231.1 for parthenolide and m/z 186.2->92.1 for pirfenidone (IS), respectively. The calibration curve was linear over the range of 2.0-500ng/mL with a lower limit of quantitation (LLOQ) of 2.0ng/mL. Mean recovery of parthenolide in plasma was in the range of 78.2-86.6%. Intra-day and inter-day precision were both <8.3%. This method was successfully applied in pharmacokinetic study after oral and intravenous administration of parthenolide in rats. PMID- 26678177 TI - Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions. AB - Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test. PMID- 26678178 TI - Identification, isolation and characterization of potential process-related impurity and its degradation product in vildagliptin. AB - Vildagliptin is a member of a new class of oral anti-diabetic drug. One unknown impurity was identified in the range of 0.01-0.06% in different laboratory batches of vildagliptin along with known impurities by HPLC analysis. The structure of unknown impurity was proposed as (2S)-1-[2-[(3-hydroxyadamantan-1 yl)imino]acetyl]pyrrolidine-2-carbonitrile (Impurity-E) using LC/ESI-MS(n) study. The unknown impurity was found to be unstable in diluent (H2O:CH3CN) and degrading into another stable impurity. The degraded stable impurity was isolated from enriched reaction crude sample by semi preparative liquid chromatography. The structure of stable impurity was established using FT-IR, NMR ((1)H, (13)C and DEPT), 2D NMR (HSQC, HMBC and COSY) and mass spectral data as (8aS)-3-hydroxy octahydropyrrolo[1,2-a]piperazine-1,4-dione (Impurity-F). Impurity identification, abnormal behaviour of impurity-E, isolation of impurity-F, fragmentation mechanism and structural elucidation were also discussed. PMID- 26678180 TI - Cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry for screening bioactive capilliposide C metabolites generated by rat intestinal microflora. AB - Many plant-derived glycosides are used as medications. It is common that these glycosides show poor intestinal absorption but their metabolites generated by intestinal microflora demonstrate strong bioactivity. Hence, it is crucial to develop a method for the identification and characterization of the metabolites, and consequently reveal the pathway in which the glycosides are processed in gut. In this study, cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC QTOF-MS/MS) were developed for rapid discovery and evaluation of the metabolites of a glycoside compound, capilliposide C (LC-C). 92.7% of LC-C was biotransformed by rat intestinal microflora after 36-h incubation at 37 degrees C. Human cancer cell lines HepG2, PC-3 and A549 was treated with metabolites pool, respectively, which was followed by cell viability assays and characterization of metabolites using UHPLC-QTOF-MS/MS. As a result, significant cytotoxicity was observed for the metabolites pool, from which six metabolites were identified. Based on the metabolites identified, deglycosylation and esterolysis were proposed as the major metabolic pathways of LC-C in rat intestinal microflora. In addition, M4, an esterolysis product of LC-C, was obtained and evaluated for its bioactivity in vitro. As a result, M4 exhibited a reduction in cell viability in HepG2 with an IC50 value of 17.46+/-1.55MUg/mL. PMID- 26678179 TI - A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues. AB - Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2MUm, 2.0*100mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10ng/mL and is shown to be linear up to 3000ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72h after administration of PEGylated liposomal doxorubicin (Doxil((r)); PLD) at 6mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin. PMID- 26678181 TI - A fast and reliable method for GHB quantitation in whole blood by GC-MS/MS (TQD) for forensic purposes. AB - Gamma-hydroxybutyric acid (GHB) is an endogenous compound with a story of clinical use since the 1960s. However, due to its secondary effects, it has become a controlled substance, entering the illicit market. A fully validated, sensitive and reproducible method for the quantification of GHB by methanolic precipitation and GC-MS/MS (TQD) in whole blood is presented. Using 100MUL of whole blood, obtained results included a LOD and LLOQ of 0.1mg/L and a recovery of 86% in a working range between 0.1 and 100mg/L. This method is sensitive and specific to detect the presence of GHB in small amounts of whole blood (both ante mortem or post-mortem), and is, to the authors' knowledge, the first GC-MS-MS TQD method that uses different precursor ions and product ions for the identification of GHB and GHB-D6 (internal standard). Hence, this method may be especially useful for the study of endogenous values in this biological sample. PMID- 26678183 TI - Correcting epicanthal folds by using asymmetric Z-plasty with a two curve design. PMID- 26678184 TI - Sugar: a taxing problem? PMID- 26678185 TI - The Lancet Oncology: 15 years and counting.... PMID- 26678186 TI - Distinguishing activity from progress. PMID- 26678182 TI - Mutation of p53 Gene and Its Correlation with the Clinical Outcome in Dogs with Lymphoma. AB - BACKGROUND: p53 plays a key role in the apoptotic event induced by chemotherapeutic agents. Mutation of p53 gene has been observed in various spontaneous tumors in humans and is associated with a poor prognosis. p53 abnormalities have been evaluated in several tumors in dogs; however, the association of p53 gene mutation with clinical outcome in dogs with lymphoma has not been documented. HYPOTHESIS/OBJECTIVES: The aim of this study was to examine p53 mutation in canine lymphoma cells and its association with the clinical outcome. ANIMALS: Forty-three dogs with previously untreated high-grade lymphoma referred to the University of Tokyo were included in this study. METHODS: Prospective cohort study. We examined p53 gene (exon 4-8) mutation in the tumor tissues from 43 dogs with lymphoma using PCR-SSCP (polymerase chain reaction single-strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. RESULTS: Of the 43 dogs, 7 dogs (16%) had p53 mutation, whereas 36 dogs (84%) were devoid of p53 mutation. Overall response rate after remission induction was significantly lower (33% versus 88%, P = .002) in dogs with lymphomas having p53 mutation than those with lymphomas devoid of p53 mutation. Overall survival time was significantly shorter (67 days versus 264 days, P = .004) in dogs with lymphoma with p53 mutation than those with lymphoma retaining wild-type p53. CONCLUSION AND CLINICAL IMPORTANCE: Mutations of p53 gene were detected in a proportion of canine lymphoma cells from untreated dogs and can be associated with a poor prognosis. PMID- 26678187 TI - 15 years of The Lancet Oncology. PMID- 26678188 TI - Influencing cancer treatment. PMID- 26678189 TI - Precision oncology: where next? PMID- 26678190 TI - Fantastic voyage: the future of cancer diagnostics. PMID- 26678191 TI - Laughter is the best form of therapy. PMID- 26678194 TI - Cancer in the transgender community. PMID- 26678195 TI - TRIBE study: are all three cytotoxic drugs crucial? PMID- 26678196 TI - TRIBE study: are all three cytotoxic drugs crucial? - Authors' reply. PMID- 26678197 TI - Precision medicine: lessons learned from the SHIVA trial. PMID- 26678198 TI - Precision medicine: lessons learned from the SHIVA trial. PMID- 26678199 TI - Precision medicine: lessons learned from the SHIVA trial. PMID- 26678200 TI - Precision medicine: lessons learned from the SHIVA trial - Authors' reply. PMID- 26678201 TI - Maintenance treatment in metastatic colorectal cancer. PMID- 26678202 TI - Maintenance treatment in metastatic colorectal cancer. PMID- 26678203 TI - Maintenance treatment in metastatic colorectal cancer - Authors' reply. PMID- 26678204 TI - Survival of patients with metastatic breast cancer with or without locoregional therapy. PMID- 26678205 TI - Survival of patients with metastatic breast cancer with or without locoregional therapy. PMID- 26678206 TI - Survival of patients with metastatic breast cancer with or without locoregional therapy. PMID- 26678207 TI - Survival of patients with metastatic breast cancer with or without locoregional therapy. PMID- 26678208 TI - Survival of patients with metastatic breast cancer with or without locoregional therapy - Authors' reply. PMID- 26678209 TI - Correction to Lancet Oncol 2015; 16: 1045. PMID- 26678210 TI - Correction to Lancet Oncol 2015; 16: 1355, 1363. PMID- 26678211 TI - Correction to Lancet Oncol 2015; 16: 1499. PMID- 26678212 TI - Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. AB - The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials. PMID- 26678213 TI - Classification of treatment-related mortality in children with cancer: a systematic assessment. AB - Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (kappa=0.83, 95% CI 0.60-1.00) and paediatric oncologists (0.84, 0.63-1.00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0.92, 0.78-1.00). Our approach should allow comparison of treatment-related mortality across trials and across time. PMID- 26678214 TI - Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention. AB - Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets. PMID- 26678215 TI - A risk management approach for imaging biomarker-driven clinical trials in oncology. AB - Imaging has steadily evolved in clinical cancer research as a result of improved conventional imaging methods and the innovation of new functional and molecular imaging techniques. Despite this evolution, the design and data quality derived from imaging within clinical trials are not ideal and gaps exist with paucity of optimised methods, constraints of trial operational support, and scarce resources. Difficulties associated with integrating imaging biomarkers into trials have been neglected compared with inclusion of tissue and blood biomarkers, largely because of inherent challenges in the complexity of imaging technologies, safety issues related to new imaging contrast media, standardisation of image acquisition across multivendor platforms, and various postprocessing options available with advanced software. Ignorance of these pitfalls directly affects the quality of the imaging read-out, leading to trial failure, particularly when imaging is a primary endpoint. Therefore, we propose a practical risk-based framework and recommendations for trials driven by imaging biomarkers, which allow identification of risks at trial initiation to better allocate resources and prioritise key tasks. PMID- 26678217 TI - Oxolinic Acid Binding at Goethite and Akaganeite Surfaces: Experimental Study and Modeling. AB - Oxolinic acid (OA) is a widely used quinolone antibiotic in aquaculture. In this study, its interactions with synthetic goethite (alpha-FeOOH) and akaganeite (beta-FeOOH) particle surfaces were monitored to understand the potential fate of OA in marine sediments where these phases occur. Batch sorption experiments, liquid chromatography (LC) analyses of supernatants, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and multisite complexation (MUSIC) modeling were used to monitor OA binding at these particle surfaces. Both LC and ATR-FTIR showed that adsorption did not degrade OA, and that OA adsorption was largely unaffected by NaCl concentrations (10-1000 mM). This was explained further by ATR-FTIR suggesting the formation of metal-bonded complexes at circumneutral to low pHc = -log [H(+)] and with a strongly hydrogen-bonded complex at high pHc. The stronger OA binding to akaganeite can be explained both by the higher isoelectric point/point-of-zero charge (9.6-10) of this mineral than of goethite (9.1-9.4), and an additional OA surface complexation mechanism at the (010) plane. Geminal sites (=Fe(OH2)2(+)) at this plane could be especially reactive for metal-bonded complexes, as they facilitate a mononuclear six-membered chelate complex via the displacement of two hydroxo/aquo groups at the equatorial plane of a single Fe octahedron. Collectively, these findings revealed that Fe-oxyhydroxides may strongly contribute to the fate and transport of OA-type antibacterial agents in marine sediments and waters. PMID- 26678216 TI - Hydride Attack on a Coordinated Ferric Nitrosyl: Experimental and DFT Evidence for the Formation of a Heme Model-HNO Derivative. AB - Heme-HNO species are crucial intermediates in several biological processes. To date, no well-defined Fe heme-HNO model compounds have been reported. Hydride attack on the cationic ferric [(OEP)Fe(NO)(5-MeIm)]OTf (OEP = octaethylporphyrinato dianion) generates an Fe-HNO product that has been characterized by IR and (1)H NMR spectroscopy. Results of DFT calculations reveal a direct attack of the hydride on the N atom of the coordinated ferric nitrosyl. PMID- 26678219 TI - Reversed shunting in CREST syndrome. AB - The patent foramen ovale (PFO) is one of the most common congenital defects and may as well stand for "potential for opening" in addition to patent foramen ovale. Although patients are usually asymptomatic because the defect is flap-like and does not permit significant left-to-right shunting, the pathological conditions that result in cardiac rotation or higher than normal right atrial pressures can reverse the normal left atrial to right atrial pressure gradient and cause a right-to-left shunt through a PFO. Pulmonary complications of systemic sclerosis (SSc) are common, and are the leading cause of SSc-related death. The most common pulmonary manifestations of SSc are pulmonary hypertension (PAH), interstitial lung disease, and any combination thereof. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:390-391, 2016. PMID- 26678218 TI - Isotopic exchange on solid-phase micro extraction fiber in sediment under stagnant conditions: Implications for field application of performance reference compound calibration. AB - An overlooked issue for field application of in situ performance reference compound (PRC) calibration methods is the validity of the assumption that both the sorption of a target compound and desorption of its corresponding PRC follow the first-order kinetics with the same rate constants under stagnant conditions. In the present study, disposable polydimethylsiloxane fibers of 2 sizes (7 and 35 um) impregnated with 8 (13) C-labeled or deuterated PRCs were statically deployed into different marine sediments, from which the kinetics for sorption of the target compounds and desorption of the PRCs were characterized. Nonsymmetrical profiles were observed for exchange of the target analytes and their corresponding PRCs in sediment under stagnant conditions. The hysteretic desorption of PRCs in the kinetic regime may be ascribed to the low chemical potential between the fiber and sediment porewater, which reflects the inability of water molecules to rapidly diffuse through sediment to solvate the PRCs in the aqueous layer around the fiber surface. A moderate correlation (r = 0.77 and r = 0.57, p < 0.05 for both regressions) between the PRC-calibrated equilibrium concentrations of 1,1-dichloro-2,2-bis-(chlorophenyl) ethylene (p,p'-DDE) and polychlorinated biphenyl (PCB)-153 and the lipid normalized levels in worms (Neanthes arenaceodentata) was obtained in co-exposure tests under simulating field conditions, probably resulting from slightly overestimated bioavailability because of the hysteretic desorption of PRCs and toxic effects. Environ Toxicol Chem 2016;35:1978-1985. (c) 2015 SETAC. PMID- 26678221 TI - Corrigendum. PMID- 26678222 TI - Alternatively spliced isoforms of IL-32 differentially influence cell death pathways in cancer cell lines. AB - Alternative splicing is a biological mechanism that enables the synthesis of several isoforms with different or even opposite functions. This process must be tightly regulated to prevent unwanted isoform expression favoring pathological processes. Some isoforms of interleukin 32 (IL-32) are reported to be more potent in inducing inflammation, however the role in cell death remains to be investigated. This study demonstrates that IL-32gamma and IL-32beta can induce caspase-8-dependent cell death whereas this was not observed for IL-32alpha. Overexpression of IL-32beta or IL-32gamma but not IL-32alpha, resulted in enhanced expression of the survival cytokine IL-8. Furthermore, restoring the IL 8 signaling pathway by overexpressing CXCR1 in HEK293 cells, rescued IL-32beta but not IL-32gamma-induced cell death. Interestingly, IL-32gamma was able to downregulate CXCR1 and thereby induce cell death. Subsequent studies into the role of IL-32 in thyroid cancer (TC) revealed that several IL-32 isoforms, IL-8, and CXCR1 are expressed in TC cell lines and specimens. Remarkably, TC cell lines were found to produce high concentrations of IL-8, indicating an important role for IL-8 in the survival-signaling pathway in these cells. Intriguingly, a significant correlation between the IL-8 receptor CXCR1 and IL-32gamma was observed in TC specimens, while this was not observed for the other IL-32 splice variants. Blocking IL-32 alternative splicing by Isoginkgetin resulted in predominant expression of IL-32gamma splice variants and cell death in TC cell lines. All together, modulation of IL-32 alternative splicing could represent a novel strategy for the treatment of malignancies, in particular thyroid cancer. PMID- 26678220 TI - Evolution-development congruence in pattern formation dynamics: Bifurcations in gene expression and regulation of networks structures. AB - Search for possible relationships between phylogeny and ontogeny is important in evolutionary-developmental biology. Here we uncover such relationships by numerical evolution and unveil their origin in terms of dynamical systems theory. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, gene regulation networks are evolved under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Both in the evolution and development pattern changes consist of several epochs where stripes are formed in a short time, while for other temporal regimes, pattern hardly changes. In evolution, these quasi-stationary regimes are generations needed to hit relevant mutations, while in development, they are due to some gene expression that varies slowly and controls the pattern change. The morphogenesis is regulated by combinations of feedback or feedforward regulations, where the upstream feedforward network reads the external morphogen gradient, and generates a pattern used as a boundary condition for the later patterns. The ordering from up to downstream is common in evolution and development, while the successive epochal changes in development and evolution are represented as common bifurcations in dynamical-systems theory, which lead to the evolution-development congruence. Mechanism of exceptional violation of the congruence is also unveiled. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis. PMID- 26678223 TI - Trans-dichlorooxovandium (IV) complex as a novel photoinducible DNA interstrand crosslinker for cancer therapy. AB - Although DNA interstrand crosslinking (ICL) agents such as mitomycin C, cisplatin and psoralen serve as potent anticancer drugs, these agents are known to have dose-limiting toxic effects on normal cells. Moreover, tumor resistance to these agents has been reported. Here, we show that trans-dichlorooxovanadium (IV) complex of pyrenyl terpyridine (VDC) is a novel photoinducible DNA crosslinking agent. By a combination of in vitro and ex vivo experiments including plasmid based assays, we find that VDC forms monoadducts on the DNA and can be activated by UV-A and visible light to generate DNA interstrand crosslinks. VDC efficiently activates Fanconi anemia (FA) pathway of DNA interstrand crosslink repair. Strikingly, photoinduction of VDC induces prolonged activation of cell cycle checkpoint and a high degree of cell death in homologous recombination (HR)/ICL repair defective cells. Moreover, VDC specifically targets cells that express pathological RAD51C mutants. These data imply that VDC can be potentially used for cancer therapy and suggest that tumors arising in patients with gene mutations in FA and HR repair pathway can be specifically targeted by a photoactivatable VDC. PMID- 26678224 TI - Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice. AB - Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 ug of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL 1beta, IL-6, TNFalpha, HMGB1 and active TGFbeta1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL 1beta, IL-6, TNFalpha, HMGB1 and TGFbeta1) and cytokine receptors (TNFalphaR1 and TGFbetaR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. PMID- 26678227 TI - Changes Afoot, and the Pediatric SUPPORT Decision. PMID- 26678225 TI - Disrupted rich club network in behavioral variant frontotemporal dementia and early-onset Alzheimer's disease. AB - In network analysis, the so-called "rich club" describes the core areas of the brain that are more densely interconnected among themselves than expected by chance, and has been identified as a fundamental aspect of the human brain connectome. This is the first in-depth diffusion imaging study to investigate the rich club along with other organizational changes in the brain's anatomical network in behavioral frontotemporal dementia (bvFTD), and a matched cohort with early-onset Alzheimer's disease (EOAD). Our study sheds light on how bvFTD and EOAD affect connectivity of white matter fiber pathways in the brain, revealing differences and commonalities in the connectome among the dementias. To analyze the breakdown in connectivity, we studied three groups: 20 bvFTD, 23 EOAD, and 37 healthy elderly controls. All participants were scanned with diffusion-weighted magnetic resonance imaging (MRI), and based on whole-brain probabilistic tractography and cortical parcellations, we analyzed the rich club of the brain's connectivity network. This revealed distinct patterns of disruption in both forms of dementia. In the connectome, we detected less disruption overall in EOAD than in bvFTD [false discovery rate (FDR) critical Pperm = 5.7 * 10(-3) , 10,000 permutations], with more involvement of richly interconnected areas of the brain (chi-squared P = 1.4 * 10(-4) )-predominantly posterior cognitive alterations. In bvFTD, we found a greater spread of disruption including the rich club (FDR critical Pperm = 6 * 10(-4) ), but especially more peripheral alterations (chi squared P = 6.5 * 10(-3) ), particularly in medial frontal areas of the brain, in line with the known behavioral socioemotional deficits seen in these patients. PMID- 26678226 TI - T2R38 genotype is correlated with sinonasal quality of life in homozygous DeltaF508 cystic fibrosis patients. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients. METHODS: DeltaF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment. RESULTS: A total of 49 DeltaF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05). CONCLUSION: Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in DeltaF508 homozygous CF patients. PMID- 26678228 TI - Why Wolves? PMID- 26678229 TI - A 15-Year-Old Girl with a History of Depression and Weight Loss. PMID- 26678230 TI - Care of the Child with Special Needs. AB - About 18% of all children in the United States have complex medical diseases, require technologic support, and/or have developmental or intellectual disability. These children require routine or maintenance care through the medical-home model. However, due to a lack of physicians, time, and financial constraints it is difficult for many of those children to obtain this care. Pediatricians often lack the training (or comfort level) to care for these children in the office setting. Having an understanding of what outpatient care entails to better serve this population will help the pediatrician provide a medical-home setting for children with special needs and their families. PMID- 26678231 TI - A 17-Year-Old Boy with Cardiac Arrest Occurring during Exercise. PMID- 26678232 TI - New-Onset Seizures in an Infant. PMID- 26678233 TI - Sudden Cardiac Death in Children and Adolescents. PMID- 26678234 TI - Diagnostic Approach to Limp in Children. AB - "Limp" is a common complaint of children presenting to the emergency department or physician's office. For most patients presenting with limp, the diagnosis and management can be completed in the physician's office or emergency department by gathering a detailed history, performing a careful physical examination, and requesting a few laboratory and imaging studies. This article reviews common causes of atraumatic limp in children and discusses the evaluation and management of these conditions. PMID- 26678235 TI - Chest Pain in Pediatrics. AB - Chest pain in children and adolescents frequently involves referral to a pediatric cardiologist. The etiology of chest pain in pediatrics is broad, and the vast majority of cases are not due to underlying cardiac pathology. However, evaluations are often pursued due to fear about missing a potentially serious cardiac diagnosis, which may lead to sudden cardiac death. The management of these patients can lead to extensive investigations, medical visits, and hospitalizations, which is costly and unnecessary in many cases. This article reviews noncardiac and cardiac etiologies of chest pain, highlights pertinent details of the patient history and physical examination, discusses the evaluation of patients with chest pain, and identifies when referral to a pediatric cardiologist is recommended. PMID- 26678236 TI - Palpitations and Arrhythmias and Sudden Cardiac Arrest/Sudden Cardiac Death in Children and Adolescents. AB - Palpitations are a common complaint, particularly in teenagers, with etiologies ranging from no detectable cardiac dysrhythmia to life-threatening dysrhythmias. Despite the fact that as many as 50% of children and adolescents may be asymptomatic prior to experiencing sudden cardiac arrest, the occurrence of palpitations may afford the opportunity to detect a potentially lethal arrhythmia condition. This article discusses the evaluation of palpitations in the pediatric population by focusing on the two most common life-threatening arrhythmia diagnoses that may initially manifest itself in the pediatric population with the chief complaint of palpitations-Wolff-Parkinson-White syndrome and the long QT syndrome. PMID- 26678237 TI - Syncope in Children and Adolescents. AB - Syncope is an abrupt loss of consciousness and postural tone frequently due to disturbance of the normal autonomic nervous system reflexive mechanisms in regulating peripheral vascular resistance, blood pressure, and heart rate. This leads to a transient decrease in cerebral blood flow. It is a common presenting complaint in children and adolescents. In many cases, there is a characteristic preceding prodrome of dizziness, nausea, diaphoresis, and pallor. Although most cases of syncope are benign in etiology, it frequently causes stress and anxiety in regard to potential cardiovascular disease and possible sudden cardiac death. With careful screening by detailed patient history, comprehensive physical examination, and electrocardiogram (ECG), a significant majority of patients with serious underlying cardiac conditions will be identified. The routine use of echocardiography, ambulatory ECG, tilt-table tests, and exercise stress tests is expensive and frequently of low diagnostic yield. With benign forms of syncope, patient reassurance and education should be the first-line treatment. PMID- 26678238 TI - Strategies for the Prevention of Sudden Cardiac Death in Children and Adolescents. AB - Sudden cardiac arrest (SCA) or sudden cardiac death (SCD) in children and adolescents is a devastating event. Although the true incidence is unclear, the etiologies are not. Strategies for prevention include both primary as well as secondary prevention strategies, and these strategies are not mutually exclusive. From a primary prevention standpoint, many of the episodes of SCA or SCD may occur without any antecedent warning signs and in the absence of an important family history. There are a subset of children and adolescents who may have antecedent warning signs and symptoms such as syncope with exercise, chest pain, and palpitations. This article addresses those symptoms specifically and in more detail to help guide the generalist with regard to a framework of risk stratification. The importance of secondary prevention is also discussed. It is critically important to promote and advocate for cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) education for everyone, including all students prior to graduation from high school. CPR and AEDs save the lives of children, adolescents, and adults. A society that is able and willing to perform CPR will result in an increase in the incidence of lay-rescuer CPR and will undoubtedly save more lives. PMID- 26678239 TI - Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old. AB - BACKGROUND AND AIM: Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability. METHODS: Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55-89 years were selected. The degrees of fatty liver were categorized into mild and moderate-severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence. RESULTS: A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors (all P < 0.05). After adjusting for age, estradiol, and total testosterone, increased quartiles of FSH were associated with significantly decreased odds ratios of mild and moderate-severe groups (both P for trends <0.05). After further adjustment for waist circumference and HOMA-IR, FSH was no longer associated with mild hepatic steatosis. The association of FSH with moderate-severe hepatic steatosis was attenuated by waist circumference and HOMA IR but persisted in the fully adjusted model (P for trend <0.01). CONCLUSION: Follicle-stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate severe hepatic steatosis with FSH. PMID- 26678240 TI - Incomplete Kawasaki disease in a 12-month-old girl presenting with cardiac murmur and iron deficiency anemia. AB - Kawasaki disease (KD) is an acute necrotizing vasculitis that occurs in children <5 years of age. The cause of KD remains unknown, but various complications, including dilatation of the coronary arteries, can occur. Coronary artery aneurysm or ectasia are the most important complications of KD. Children with suspected KD who do not fulfill the diagnostic criteria may have incomplete KD. Given that incomplete KD is associated with delayed diagnosis and treatment, children with incomplete KD have a high risk of cardiovascular complications. Meanwhile, iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies in the world. Children with IDA are prone to infection and inflammation. We report the case of a 12-month-old girl with incomplete KD who presented with cardiac murmur and severe IDA. PMID- 26678241 TI - Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines. AB - Lung cancer is the leading cause of cancer death in the world, and cigarette smoking is its main cause. Oral cavity cancer is another debilitating and often fatal cancer closely linked to tobacco product use. While great strides have been made in decreasing tobacco use in the United States and some other countries, there are still an estimated 1 billion men and 250 million women in the world who are cigarette smokers and there are hundreds of millions of smokeless tobacco users, all at risk for cancer. Worldwide, lung cancer kills about three people per minute. This Account focuses on metabolites and biomarkers of two powerful tobacco-specific nitrosamine carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) and N'-nitrosonornicotine (NNN), considered to be among the main causes of lung cancer and oral cavity cancer in people who use tobacco products. Three properties of NNK and NNN are critical for successful biomarker studies: they are present in all tobacco products, they are tobacco-specific and are not found in any other product, and they are strong carcinogens. NNK and NNN are converted in humans to urinary metabolites that can be quantified by mass spectrometry as biomarkers of exposure to these carcinogens. They are also metabolized to diazonium ions and related electrophiles that react with DNA to form addition products that can be detected and quantified by mass spectrometry. These urinary metabolites and DNA addition products can serve as biomarkers of exposure and metabolic activation, respectively. The biomarkers of exposure, in particular the urinary NNK metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanol (NNAL) and its glucuronides, have been extensively applied to document tobacco-specific lung carcinogen uptake in smokers and nonsmokers exposed to secondhand tobacco smoke. Highly sensitive mass spectrometric methods have been developed for quantitative analysis of these NNK metabolites as well as metabolites of NNN in human urine, blood, and toenails. Urinary and serum NNAL have been related to lung cancer risk, and urinary NNN has been related to esophageal cancer risk in prospective epidemiology studies. These results are consistent with carcinogenicity studies of NNK, NNAL, and NNN in rats, which show that NNK and NNAL induce mainly lung tumors, while NNN causes tumors of the esophagus and oral cavity. Biomarkers of metabolic activation of NNK and NNN applied in human studies include the metabolism of deuterium labeled substrates to distinguish NNK and NNN metabolism from that of nicotine and the determination of DNA and hemoglobin adducts in tissues, blood, and oral cells from people exposed to tobacco products. As these methods are continually improved in parallel with the ever increasing sensitivity and selectivity of mass spectrometers, development of a comprehensive biomarker panel for identifying tobacco users at high risk for cancer appears to be a realistic goal. Targeting high risk individuals for smoking cessation and cancer surveillance can potentially decrease the risk of developing fatal cancers. PMID- 26678242 TI - Propensity score and doubly robust methods for estimating the effect of treatment on censored cost. AB - The estimation of treatment effects on medical costs is complicated by the need to account for informative censoring, skewness, and the effects of confounders. Because medical costs are often collected from observational claims data, we investigate propensity score (PS) methods such as covariate adjustment, stratification, and inverse probability weighting taking into account informative censoring of the cost outcome. We compare these more commonly used methods with doubly robust (DR) estimation. We then use a machine learning approach called super learner (SL) to choose among conventional cost models to estimate regression parameters in the DR approach and to choose among various model specifications for PS estimation. Our simulation studies show that when the PS model is correctly specified, weighting and DR perform well. When the PS model is misspecified, the combined approach of DR with SL can still provide unbiased estimates. SL is especially useful when the underlying cost distribution comes from a mixture of different distributions or when the true PS model is unknown. We apply these approaches to a cost analysis of two bladder cancer treatments, cystectomy versus bladder preservation therapy, using SEER-Medicare data. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26678244 TI - Lunate-triquetral coalition in an Australian setting. PMID- 26678243 TI - Suppressing activity of staurosporine from Streptomyces sp. MJM4426 against rice bacterial blight disease. AB - AIM: To identify the active compounds from the Streptomyces sp. MJM4426 that can protect rice from bacterial blight disease (BB), and to evaluate the potential of this Streptomyces strains and the compound for biocontrol of rice bacterial blight disease. METHODS AND RESULTS: The ethyl acetate extract of Streptomyces sp. MJM4426 can significantly protect rice leaf explants from the infection of Xanthomonas oryzae pv. oryzaeKACC 10331 (Xoo), the pathogen which cause BB. To identify the active compounds, the ethyl acetate extract of Streptomyces sp. MJM4426 was fractionated through a Sephadex LH-20 column chromatography, and further purified by preparative HPLC guided by the inhibitory activity against BB in rice leaf explants. UPLC-Q-TOF/MS analysis showed the active compound displayed its m/z values at [M+H](+) 467.2086 and [M+FA-H](-) 511.1963, and the molecular formula was estimated as C28 H26 N4 O3 which is identical to commercial standard staurosporine. In this study, the isolated staurosporine dramatically suppressed bacterial blight in rice leaf explants with the lowest concentration at 12.5 MUmol l(-1) , however, it exhibited low inhibitory activity against Xoo with the MIC value at 256 MUg ml(-1) . In addition, greenhouse study showed both crude extract and purified staurosporine can suppress the bacterial blight at the concentration of 5000 and 200 MUg ml(-1) respectively. CONCLUSION: Streptomyces sp. MJM4426 can protect rice leaf explants from the infection of Xoo by producing staurosporine, but not by direct inhibitory activity against Xoo. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that staurosporine can protect rice leaf against bacterial blight disease and showed the potential of Streptomyces sp. MJM4426 as an alternative to chemical bactericide for bacterial blight disease in rice. PMID- 26678245 TI - Belatacept for renal rescue in lung transplant patients. AB - Renal failure causes morbidity and mortality after lung transplantation and is aggravated by exposure to nephrotoxic immunosuppressant (IS) drugs. We report an off-label experience using belatacept for lung transplant recipients with severe renal insufficiency to reduce nephrotoxic IS exposure. We analyzed data retrospectively from a consecutive series of lung transplant patients with renal insufficiency in whom belatacept treatment was initiated between June 2012 and June 2014 at the University of Maryland Medical Center. Eight patients received belatacept because of acute or chronic renal insufficiency (median) GFR 24 (IQR 18-26). Glomerular filtration rate (GFR) remained stable in two patients and increased in five. One patient with established renal and respiratory failure received only the induction dose of belatacept and died 4 months later of respiratory and multisystem organ failure. Calcineurin inhibitor or sirolimus exposure was safely withheld or reduced without moderate or severe acute rejection during ongoing belatacept in the other seven patients. FEV1 remained stable over the 6-month study interval. Belatacept use appears to permit safe transient reduction in conventional immunosuppressive therapy and was associated with stable or improved renal function in a small retrospective series of lung transplant recipients with acute or chronic renal insufficiency. PMID- 26678246 TI - Maximum-biomass concentration prediction for Bifidobacteria in the pH-controlled fed-batch culture. AB - Our objective was to systematically study the relationship between maximum biomass concentration of different Bifidobacteria and total-acid anions accumulation, and develop a prediction equation for the maximum biomass concentration in the fed-batch culture at pH-controlled 7.0. The accumulation of acid anions and the consumption of nutrients of various strains were evaluated. In addition, minimum inhibitory concentrations (MICs) of acid anions on a range of strains were examined at pH 7.0. The inhibition of acid anions, which had the same MIC as sodium chloride, was due to the osmotic pressure under pH 7.0 conditions. Moreover, the concentration of total-acid anions completely inhibiting each strain in the fed-batch culture at pH-controlled 7.0 had no significant differences with the MIC of acid anions for the corresponding strains. The osmotic pressures under two conditions were not significantly different. Finally, the maximum biomass concentration of Bifidobacteria was found to be closely related to biomass yield per unit of acid anion produced (YX/P ) and MIC (C) which were needed for the prediction, and different strains exhibited marked correlation (P ? 0.01, R = 0.985). An equation for the prediction of the maximum biomass concentration was developed as follows: Xmax -X0 = (0.71 +/- 0.03).YX/P .C. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides further insights into the inhibition of Bifidobacteria by dissociated acid anions (the dissociated form) at pH 7.0. The high correlation between different strains suggested that the equation established in this paper is appropriate for different strains of Bifidobacteria. The prediction equation could be used to guide practical production in the preparation of materials, the control of the end of fermentation and production plans for further products such as freeze dried powder of Bifidobacteria or food fermentation. PMID- 26678247 TI - The complete plastid genome of the middle Asian endemic of Stipa lipskyi (Poaceae). AB - The structure of the Stipa lipskyi (GenBank accession no. KT692644) plastid genome is similar to that of closely related Poaceae species: it has a total length of 137 755 bp, the base composition of the plastome is the following: A (30.7%), C (19.3%), G (19.4%) and T (30.5%). The S. lipskyi plastid genome contains 71 genes, excluding second IR region. A complete plastome sequence of S. lipskyi will help the development of primers for examining phylogeny and hybridization events in this taxonomically difficult genus. PMID- 26678248 TI - Enhancement of Spike-Timing-Dependent Plasticity in Spiking Neural Systems with Noise. AB - Synaptic plasticity is widely recognized to support adaptable information processing in the brain. Spike-timing-dependent plasticity, one subtype of plasticity, can lead to synchronous spike propagation with temporal spiking coding information. Recently, it was reported that in a noisy environment, like the actual brain, the spike-timing-dependent plasticity may be made efficient by the effect of stochastic resonance. In the stochastic resonance, the presence of noise helps a nonlinear system in amplifying a weak (under barrier) signal. However, previous studies have ignored the full variety of spiking patterns and many relevant factors in neural dynamics. Thus, in order to prove the physiological possibility for the enhancement of spike-timing-dependent plasticity by stochastic resonance, it is necessary to demonstrate that this stochastic resonance arises in realistic cortical neural systems. In this study, we evaluate this stochastic resonance phenomenon in the realistic cortical neural system described by the Izhikevich neuron model and compare the characteristics of typical spiking patterns of regular spiking, intrinsically bursting and chattering experimentally observed in the cortex. PMID- 26678249 TI - An Auditory-Tactile Visual Saccade-Independent P300 Brain-Computer Interface. AB - Most P300 event-related potential (ERP)-based brain-computer interface (BCI) studies focus on gaze shift-dependent BCIs, which cannot be used by people who have lost voluntary eye movement. However, the performance of visual saccade independent P300 BCIs is generally poor. To improve saccade-independent BCI performance, we propose a bimodal P300 BCI approach that simultaneously employs auditory and tactile stimuli. The proposed P300 BCI is a vision-independent system because no visual interaction is required of the user. Specifically, we designed a direction-congruent bimodal paradigm by randomly and simultaneously presenting auditory and tactile stimuli from the same direction. Furthermore, the channels and number of trials were tailored to each user to improve online performance. With 12 participants, the average online information transfer rate (ITR) of the bimodal approach improved by 45.43% and 51.05% over that attained, respectively, with the auditory and tactile approaches individually. Importantly, the average online ITR of the bimodal approach, including the break time between selections, reached 10.77 bits/min. These findings suggest that the proposed bimodal system holds promise as a practical visual saccade-independent P300 BCI. PMID- 26678250 TI - A Two-Stage Combining Classifier Model for the Development of Adaptive Dialog Systems. AB - This paper proposes a statistical framework to develop user-adapted spoken dialog systems. The proposed framework integrates two main models. The first model is used to predict the user's intention during the dialog. The second model uses this prediction and the history of dialog up to the current moment to predict the next system response. This prediction is performed with an ensemble-based classifier trained for each of the tasks considered, so that a better selection of the next system can be attained weighting the outputs of these specialized classifiers. The codification of the information and the definition of data structures to store the data supplied by the user throughout the dialog makes the estimation of the models from the training data and practical domains manageable. We describe our proposal and its application and detailed evaluation in a practical spoken dialog system. PMID- 26678251 TI - Transvaginal ultrasound examination of the endometrium in postmenopausal women without vaginal bleeding. AB - OBJECTIVES: To estimate in gynecologically asymptomatic postmenopausal women with and without hormone replacement therapy (HRT) undergoing transvaginal ultrasound examination the prevalence of: endometrial thickness >= 5.0 mm, intrauterine focal lesions if endometrial thickness is >= 5.0 mm, and premalignant and malignant endometrial changes if thickness is >= 5.0 mm and intrauterine focal lesions are present. METHODS: Invitation letters were sent to 2951 potentially eligible women recruited from a Swedish population registry; 757 replied, 514 were considered eligible (i.e. were gynecologically asymptomatic postmenopausal women aged 52-62 years with no current or previous gynecological problems) and 510 had complete information and were included. The women were examined using transvaginal ultrasound (5-9-MHz transducer). If endometrial thickness was >= 5.0 mm, saline contrast sonohysterography (SCSH) was attempted. The number, size and surface contour of intracavitary focal lesions were recorded. Women with focal lesions were offered hysteroscopic resection of the lesions. Gold standard was histology of the surgical specimen. RESULTS: The median time in menopause was 5 (range, 1-17) years. There were no substantial differences in ultrasound findings between women with HRT and those without. Sixty-two (12% (95% CI, 9-15%)) women had an endometrial thickness >= 5.0 mm. SCSH was attempted in 54 of these women, which was successful in 48 and suboptimal in one. Thirty-three (67%) of the 49 women with successful or suboptimal SCSH and one woman with spontaneous fluid in the uterine cavity had intracavitary focal lesions. Twenty-nine of these women with focal lesions underwent hysteroscopic resection of the lesion(s). Two cases of endometrial complex hyperplasia with atypia but no malignancy were found. Uterine perforation with bowel damage occurred in two women who underwent hysteroscopic surgery. CONCLUSION: About 10% of gynecologically asymptomatic postmenopausal women have a sonographic endometrial thickness >= 5.0 mm. Our results support conservative management of such women. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26678253 TI - Induced Fit in the Selection of Correct versus Incorrect Nucleotides by DNA Polymerase beta. AB - DNA polymerase beta (Pol beta) repairs single-nucleotide gapped DNA (sngDNA) by enzymatic incorporation of the Watson-Crick partner nucleotide at the gapped position opposite the templating nucleotide. The process by which the matching nucleotide is incorporated into a sngDNA sequence has been relatively well characterized, but the process of discrimination from nucleotide misincorporation remains unclear. We report here NMR spectroscopic characterization of full length, uniformly labeled Pol beta in apo, sngDNA-bound binary, and ternary complexes containing matching and mismatching nucleotide. Our data indicate that, while binding of the correct nucleotide to the binary complex induces chemical shift changes consistent with the process of enzyme closure, the ternary Pol beta complex containing a mismatching nucleotide exhibits no such changes and appears to remain in an open, unstable, binary-like conformation. Our findings support an induced-fit mechanism for polymerases in which a closed ternary complex can only be achieved in the presence of matching nucleotide. PMID- 26678252 TI - Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. AB - Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as "epigenetic clock". We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi supercentenarians (mean age: 105.6 +/- 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 +/- 7.8 years), and 47 age-matched controls (mean age: 69.8 +/- 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naive or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing. PMID- 26678255 TI - Transforming Translation: Impact of Clinical and Translational Science. PMID- 26678256 TI - Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. AB - BACKGROUND: Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy, is a rising problem worldwide. Both non pharmacological and pharmacological approaches to the prevention of gestational diabetes have been, and continue to be explored. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. It is one of the intracellular mediators of the insulin signal and correlated with insulin sensitivity in type 2 diabetes. The potential beneficial effect on improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. OBJECTIVES: To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes. SEARCH METHODS: We searched the Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, WHO ICTRP (2 November 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We sought published and unpublished randomised controlled trials, including conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes mellitus (GDM). Quasi-randomised and cross-over trials were not eligible for inclusion, but cluster designs were eligible. Participants in the trials were pregnant women. Women with pre-existing type 1 or type 2 diabetes were excluded. Trials that compared the administration of any dose of myo inositol, alone or in a combination preparation were eligible for inclusion. Trials that used no treatment, placebo or another intervention as the comparator were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, risk of bias and extracted the data. Data were checked for accuracy. MAIN RESULTS: We included four randomised controlled trials (all conducted in Italy) reporting on 567 women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials. The trials had small sample sizes and one trial only reported an interim analysis. Two trials were open-label. The overall risk of bias was unclear.For the mother, supplementation with myo-inositol was associated with a reduction in the incidence of gestational diabetes compared with control (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.29 to 0.64; three trials; n = 502 women). Using GRADE methods this evidence was assessed as low with downgrading due to unclear risk of bias for allocation concealment in two of the included trials and lack of generalisability of findings. For women who received myo-inositol supplementation, the incidence of GDM ranged from 8% to 18%; for women in the control group, the incidence of GDM was 28%, using International Association of Diabetes and Pregnancy Study Groups Consensus Panel 2010 criteria to diagnose GDM.Two trials reported on hypertensive disorders of pregnancy, a primary maternal outcome of this review. There was no clear difference in risk of hypertensive disorders of pregnancy between the myo-inositol and control groups (average RR 0.43, 95% CI 0.02 to 8.41; two trials; n = 398 women; Tau(2) = 3.23; I(2) = 69%). Using GRADE methods, this evidence was assessed as very low, with downgrading due to wide confidence intervals with very low event rates, a small sample size, and lack of blinding and unclear allocation concealment methods, and a lack of generalisability. For women who received myo-inositol the risk of hypertensive disorders of pregnancy ranged from 0% to 33%; for women in the control group the risk was 4%.For the infant, none of the included trials reported on the primary neonatal outcomes of this systematic review (large-for gestational age, perinatal mortality, mortality or morbidity composite).In terms of this review's secondary outcomes, there was no clear difference in the risk of caesarean section between the myo-inositol and control groups (RR 0.95, 95% CI 0.76 to 1.19; two trials; n = 398 women). Using GRADE methods, this evidence was assessed as low, with downgrading due to unclear risk of bias in one trial and lack of generalisability. For women who received myo-inositol supplementation, the risk of having a caesarean section ranged from 34% to 54%; for women in the control group the was 45%. There were no maternal adverse effects of therapy in the two trials that reported on this outcome (the other two trials did not report this outcome).Two trials found no clear difference in the risk of macrosomia between infants whose mothers received myo-inositol supplementation compared with controls (average RR 0.35, 95% CI 0.02 to 6.37; two trials; n = 398 infants;Tau(2) = 3.33; I(2) = 73%). Similarly, there was no clear difference between groups in terms of neonatal hypoglycaemia (RR 0.36, 95% CI 0.01 to 8.66) or shoulder dystocia (average RR 2.33, 95% CI 0.12 to 44.30, Tau(2) = 3.24; I(2) = 72%).There was a lack of data available for a large number of maternal and neonatal secondary outcomes, and no data for any of the long-term childhood or adulthood outcomes, or for health service cost outcomes. AUTHORS' CONCLUSIONS: Evidence from four trials of antenatal dietary supplementation with myo-inositol during pregnancy shows a potential benefit for reducing the incidence of gestational diabetes. No data were reported for any of this review's primary neonatal outcomes. There were very little outcome data for the majority of this review's secondary outcomes. There is no clear evidence of a difference for macrosomia when compared with control.The current evidence is based on small trials that are not powered to detect differences in outcomes including perinatal mortality and serious infant morbidity. All of the included studies were conducted in Italy which raises concerns about the lack of generalisability of the evidence to other settings. There is evidence of inconsistency and indirectness and as a result, many of the judgements on the quality of the evidence were downgraded to low or very low quality (GRADEpro Guideline Development Tool).Further trials for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors and use of myo-inositol (different doses, frequency and timing of administration) in comparison with placebo, diet and exercise or pharmacological interventions. Outcomes should include potential harms including adverse effects. PMID- 26678254 TI - In vitro cleavage of diisocyanate-glutathione conjugates by human gamma-glutamyl transpeptidase-1. AB - Isocyanates differ from many other xenobiotics in their ability to form S-linked conjugates with glutathione (GSH) through direct nucleophilic addition reactions (e.g. without enzymatic "preactivation" and/or transferase activity), potentially predisposing them to metabolism via the mercapturic acid pathway. In vivo, mono isocyanates are metabolized via the mercapturic acid pathway and excreted as N acetylated cysteine conjugates, however, the metabolism of di-isocyanates remains unclear. We assessed the ability of purified human gamma-glutamyl transpeptidase 1 (GGT-1), a primary enzyme of the mercapturic acid pathway, to cleave S-linked GSH conjugates of 4,4'-methylene diphenyl diisocyanate (MDI) and 1,6 hexamethylene diisocyanate (HDI), two widely used industrial chemicals. A combination of liquid chromatography (LC), tandem mass spectrometry (MS/MS) and hydrogen-deuterium exchange studies confirmed GGT-1 mediated formation of the 607.2 and 525.2 m/z (M + H)(+) ions corresponding to bis(cys-gly)-MDI and bis(cys gly)-HDI, respectively, the cleavage products expected from the corresponding bis(GSH)-diisocyanate conjugates. Additional intermediate metabolites and mono(cys-gly)-conjugates with partially hydrolyzed diisocyanate were also observed. Consistent with GGT enzyme kinetics, metabolism proceeded more rapidly under conditions that favored transpeptidation versus hydrolytic mechanisms of cleavage. Together the data demonstrate the capacity of human GGT-1 to cleave GSH conjugates of both aromatic and aliphatic diisocyanates, suggesting a potential role in their metabolism. PMID- 26678257 TI - Identification and characterization of toxins in the venom gland of the Chinese bird spider, Haplopelma hainanum, by transcriptomic analysis. AB - Tarantula venoms provide a model system for studying toxin selectivity, structure activity relationships and molecular evolution of peptide toxins. Previous studies have identified a large number of peptide toxins in the venom of the Chinese bird spider Haplopelma hainanum, generally regarded as a highly venomous spider. However, the lack of available RNA-seq transcriptomic and genomic data is an obstacle to understanding its venom at the molecular level. In this study, we investigated the venom gland transcriptome of H. hainanum by RNA-seq, in the absence of an available genomic sequence. We identified 201 potential toxins among 57 181 de novo assembled transcripts, including knottins, Kunitz-type toxins, enzymes and other proteins. We systematically identified most of the knottins and Kunitz-type toxins, some of which showed strongly biased expression in the venom gland, including members of the huwentoxin-1, huwentoxin-2 and magi 1 families. We also discovered several novel potential toxins. These data demonstrate the high molecular and structural diversity in the venom toxins of H. hainanum. This study offers a useful strategy for exploring the complex components of spider venoms. PMID- 26678258 TI - Characteristics of novel psychoactive substance exposures reported to New York City Poison Center, 2011-2014. AB - BACKGROUND: Novel psychoactive substances (NPS) are emerging at an unprecedented rate. Likewise, prevalence of use and poisonings has increased in recent years. OBJECTIVE: To compare characteristics of NPS exposures and non-NPS-drug-related exposures and to examine whether there are differences between exposures involving synthetic cannabinoid receptor agonists (SCRAs) and other NPS. METHODS: Poison control center data from the five counties of New York City and Long Island were examined from 2011-2014. We examined prevalence and characteristics of NPS exposures (classified as intentional abuse) and compared characteristics of cases involving SCRAs and other NPS. RESULTS: Prevalence of NPS exposures was 7.1% in 2011, rising to 12.6% in 2014. Most exposures (82.3%) involved SCRA use. The second and third most prevalent classes were phenethylamines/synthetic cathinones ("bath salts"; 10.2%) and psychedelic phenethylamines (4.3%). Compared to other drug-related exposures (i.e. involving licit and illicit drugs), those who used NPS were more likely to be younger, male, and to have not co-used other drugs (ps < 0.001). SCRA exposures increased sharply in 2014 and the mean age of users increased over time (p < 0.01). Females exposed to SCRAs were younger than males (p < 0.001), and in 2014, individuals exposed to SCRAs were more likely to report concomitant use of alcohol than users of other NPS (p = 0.010). Users of other NPS were more likely than SCRA users to report concomitant use of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)/"Molly" (p < 0.001). CONCLUSION: Exposures reported to the poison center that involve NPS are increasing and the majority involve SCRAs. These findings should inform prevention and harm reduction approaches. PMID- 26678259 TI - Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype. AB - The contribution of the contents of spermatozoa to the development of the embryo is currently being considered wider than was previously thought. Recent findings point to the participation of epigenetic marks present in the retained histones of mature spermatozoa on embryo and fetal development. Here we created a novel conditional transgenic mouse that expresses lysine (K) demethylase 1a (Kdm1a) during spermatogenesis when the testicles are subjected to heat stress. Using these animals under these conditions we were able to reduce the methylation level of histone 3 at lysines 4 and 9 (H3K4 and H3K9, respectively) in mature spermatozoa. The offspring of these transgenic mice were followed for correct development and growth after birth. We found that the offspring of males expressing Kdm1a suffered 20% of reabsorptions at Day 15 after implantation (vs 0.3% in the control). In addition, 35% of the offspring sired by these males showed some kind of abnormality (suckling defects, lack of movement coordination, dropping forelimbs, abnormal body curvature, absence of eyes, gigantisms and neuromuscular defects) and 25% died before postnatal Day 21. Some abnormalities were maintained to adulthood. These results show that alteration of epigenetic marks present in the retained histones of mature spermatozoa affect fetal development and have phenotypic consequences in the newborn. PMID- 26678260 TI - Correction: Quantifying and Mapping Global Data Poverty. PMID- 26678261 TI - An Ethylmethane Sulfonate Mutant Resource in Pre-Green Revolution Hexaploid Wheat. AB - Mutagenesis is a powerful tool used for studying gene function as well as for crop improvement. It is regaining popularity because of the development of effective and cost efficient methods for high-throughput mutation detection. Selection for semi-dwarf phenotype during green revolution has reduced genetic diversity including that for agronomically desirable traits. Most of the available mutant populations in wheat (Triticum aestivum L.) were developed in post-green revolution cultivars. Besides the identification and isolation of agronomically important alleles in the mutant population of pre-green revolution cultivar, this population can be a vital resource for expanding the genetic diversity for wheat breeding. Here we report an Ethylmethane Sulfonate (EMS) generated mutant population consisting of 4,180 unique mutant plants in a pre green revolution spring wheat cultivar 'Indian'. Released in early 1900s, 'Indian' is devoid of any known height-reducing mutations. Unique mutations were captured by proceeding with single M2 seed from each of the 4,180 M1 plants. Mutants for various phenotypic traits were identified by detailed phenotyping for altered morphological and agronomic traits on M2 plants in the greenhouse and M3 plants in the field. Of the 86 identified mutants, 75 (87%) were phenotypically stable at the M4 generation. Among the observed phenotypes, variation in plant height was the most frequent followed by the leaf morphology. Several mutant phenotypes including looped peduncle, crooked plant morphology, 'gritty' coleoptiles, looped lower internodes, and burnt leaf tips are not reported in other plant species. Considering the extent and diversity of the observed mutant phenotypes, this population appears to be a useful resource for the forward and reverse genetic studies. This resource is available to the scientific community. PMID- 26678262 TI - Freezing of Gait in Parkinson's Disease: An Overload Problem? AB - Freezing of gait (FOG) is arguably the most severe symptom associated with Parkinson's disease (PD), and often occurs while performing dual tasks or approaching narrowed and cluttered spaces. While it is well known that visual cues alleviate FOG, it is not clear if this effect may be the result of cognitive or sensorimotor mechanisms. Nevertheless, the role of vision may be a critical link that might allow us to disentangle this question. Gaze behaviour has yet to be carefully investigated while freezers approach narrow spaces, thus the overall objective of this study was to explore the interaction between cognitive and sensory-perceptual influences on FOG. In experiment #1, if cognitive load is the underlying factor leading to FOG, then one might expect that a dual-task would elicit FOG episodes even in the presence of visual cues, since the load on attention would interfere with utilization of visual cues. Alternatively, if visual cues alleviate gait despite performance of a dual-task, then it may be more probable that sensory mechanisms are at play. In compliment to this, the aim of experiment#2 was to further challenge the sensory systems, by removing vision of the lower-limbs and thereby forcing participants to rely on other forms of sensory feedback rather than vision while walking toward the narrow space. Spatiotemporal aspects of gait, percentage of gaze fixation frequency and duration, as well as skin conductance levels were measured in freezers and non freezers across both experiments. Results from experiment#1 indicated that although freezers and non-freezers both walked with worse gait while performing the dual-task, in freezers, gait was relieved by visual cues regardless of whether the cognitive demands of the dual-task were present. At baseline and while dual-tasking, freezers demonstrated a gaze behaviour that neglected the doorway and instead focused primarily on the pathway, a strategy that non freezers adopted only when performing the dual-task. Interestingly, with the combination of visual cues and dual-task, freezers increased the frequency and duration of fixations toward the doorway, compared to non-freezers. These results suggest that although increasing demand on attention does significantly deteriorate gait in freezers, an increase in cognitive demand is not exclusively responsible for freezing (since visual cues were able to overcome any interference elicited by the dual-task). When vision of the lower limbs was removed in experiment#2, only the freezers' gait was affected. However, when visual cues were present, freezers' gait improved regardless of the dual-task. This gait behaviour was accompanied by greater amount of time spent looking at the visual cues irrespective of the dual-task. Since removing vision of the lower limbs hindered gait even under low attentional demand, restricted sensory feedback may be an important factor to the mechanisms underlying FOG. PMID- 26678263 TI - A Spatiotemporal Database to Track Human Scrub Typhus Using the VectorMap Application. AB - Scrub typhus is a potentially fatal mite-borne febrile illness, primarily of the Asia-Pacific Rim. With an endemic area greater than 13 million km2 and millions of people at risk, scrub typhus remains an underreported, often misdiagnosed febrile illness. A comprehensive, updatable map of the true distribution of cases has been lacking, and therefore the true risk of disease within the very large endemic area remains unknown. The purpose of this study was to establish a database and map to track human scrub typhus. An online search using PubMed and the United States Armed Forces Pest Management Board Literature Retrieval System was performed to identify articles describing human scrub typhus cases both within and outside the traditionally accepted endemic regions. Using World Health Organization guidelines, stringent criteria were used to establish diagnoses for inclusion in the database. The preliminary screening of 181 scrub typhus publications yielded 145 publications that met the case criterion, 267 case records, and 13 serosurvey records that could be georeferenced, describing 13,739 probable or confirmed human cases in 28 countries. A map service has been established within VectorMap (www.vectormap.org) to explore the role that relative location of vectors, hosts, and the pathogen play in the transmission of mite-borne scrub typhus. The online display of scrub typhus cases in VectorMap illustrates their presence and provides an up-to-date geographic distribution of proven scrub typhus cases. PMID- 26678264 TI - Validation of the Clinical COPD Questionnaire in Taiwan. AB - Health status improvement is a critical treatment goal for physicians managing chronic obstructive pulmonary disease (COPD). Numerous instruments to measure the disease-specific health-related quality of life (HRQOL) for patients with COPD have been used in daily clinical practice. The Clinical COPD Questionnaire (CCQ) is one of these recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This study examined the psychometric properties of the CCQ in patients with COPD in Taiwan. A descriptive, cross-sectional design was conducted. Data were collected in a secondary care unit. We administered the CCQ, the modified Medical Research Council (mMRC) dyspnea scale, and the 12-item Short Form Health Survey (SF-12) for patients with COPD. Reliability was assessed using Cronbach's alpha and item-total correlation coefficients. Construct validity was assessed using confirmatory factor analysis (CFA) and testing the hypothesis that severity of dyspnea measured using the mMRC dyspnea scale is associated with the CCQ scores. Convergent validity was assessed by testing the correlation between the CCQ and the SF-12. Discriminant validity was assessed to differentiate among the classifications of COPD Groups A to D. A total of 114 subjects were recruited in the study. Cronbach's alpha was high (0.90) for the total score of the CCQ. Significant correlations were found between the CCQ scores and those of the mMRC dyspnea scale (rho = 0.67) and domains of the SF-12 (rho = -0.44 to -0.75). Furthermore, the CCQ scores showed a significant difference among the classifications of COPD Groups A to D. CFA confirmed the construct validity, with a good model fit. Good to excellent psychometric properties of the Chinese Version CCQ were demonstrated in the study. Wide usage of the Chinese Version CCQ for Taiwanese COPD patients can be recommended in daily clinical practice or clinical trials. PMID- 26678265 TI - The first complete mitochondrial genome sequence of Uraspis secunda (Perciformes: Carangidae) and its phylogenetic relationship. AB - In this study, the first complete mitochondrial genome sequence of Uraspis secunda was determined by using Illumina and Sanger sequencing technology. This genome was 16 554 bp long, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a putative control region. Twenty-eight genes were located on heavy strand, while nine genes were located on light strand. Totally two types of start codons and four kinds of stop codons were observed from 13 protein-coding genes. The overall base composition of this genome was 28.17% for A, 16.23% for G, 25.81% for T, and 29.78% for C, with a slightly higher A + T content of 53.99%. The highest A + T content (63.18%) was found in the control region of the mitochondrial genome. A phylogenetic tree was constructed based on 13 concatenated protein-coding genes, which indicated that U. secunda was closest to Parastromateus niger, and these two fish species clustered a 1. monophyletic group with Alectis ciliaris, Carangoides malabaricus and C. armatus. This study will be helpful for researches on molecular phylogeny and genetic diversity of U. secunda and the related fish species. PMID- 26678266 TI - Occlusion Location of Middle Cerebral Artery Stroke and Outcome after Endovascular Treatment. AB - BACKGROUND: The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. METHODS: Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. RESULTS: Two hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. CONCLUSIONS: Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions. PMID- 26678267 TI - Addressing corticosteroid insensitivity in adults with asthma. AB - Corticosteroids are the most effective treatment for asthma, but the therapeutic response varies markedly between individuals, with up to one third of patients showing evidence of insensitivity to corticosteroids. This article summarizes information on genetic, environmental and asthma-related factors as well as demographic and pharmacokinetic variables associated with corticosteroid insensitivity in asthma. Molecular mechanisms proposed to explain corticosteroid insensitivity are reviewed including alterations in glucocorticoid receptor subtype, binding and nuclear translocation, increased proinflammatory transcription factors and defective histone acetylation. Current therapies and future interventions that may restore corticosteroid sensitivity in asthma are discussed, including small molecule drugs and biological agents. In the future, biomarkers may be used in the clinic to predict corticosteroid sensitivity in patients with poorly controlled asthma. PMID- 26678268 TI - Multi-Scale Genomic, Transcriptomic and Proteomic Analysis of Colorectal Cancer Cell Lines to Identify Novel Biomarkers. AB - Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50's were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p<=0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients. PMID- 26678271 TI - Patient reported outcomes. PMID- 26678270 TI - Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. AB - Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET. PMID- 26678272 TI - Long-lasting, dense scotoma under light-adapted conditions in patient with multiple evanescent white dot syndrome. AB - To report the light- and dark-adapted perimetric findings in a patient with multiple evanescent white dot syndrome (MEWDS). The patient was a 25-year-old Japanese woman who underwent comprehensive ophthalmological examinations including measurements of the visual acuity, dilated ophthalmoscopy, Goldmann kinetic perimetry, electroretinography (ERG), indocyanine green fundus angiography (ICGA), and optical coherence tomography (OCT). Kinetic perimetry was performed under light- and dark-adapted conditions. The patient was diagnosed with MEWDS by the fundus and visual field findings, and the ICGA abnormalities. Light-adapted perimetry showed an enlargement of the blind spot; however, the size of the blind spot was normalized with dark-adaptation. Amplitude of cone ERG was more reduced than that of rod ERG in the affected eye. The OCT images showed multiple disruptions of the ellipsoid and interdigitation zones. These abnormalities were still present 9 months after the onset although the fundus appeared normal. These findings indicate a persistent cone-dominated dysfunction in a patient with MEWDS. PMID- 26678273 TI - Identification of new pyrrole alkaloids from the fruits of Lycium chinense. AB - Three new minor pyrrole alkaloids, 3-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1 yl]pentanedioic acid (1), (2R)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-1 methoxy-1-oxobutanoic acid (2), and methyl (2R)-[2-formyl-5-(methoxymethyl)-1H pyrrol-1-yl]-4-methylpentanoate (3) were isolated from the fruits of Lycium chinense Miller (Solanaceae), along with the known compound, methyl (2R)-[2 formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate (4). The structures of 1-4 were elucidated by analysis of their 1D- and 2D-NMR and HRMS data. The absolute configurations of 2-4, possessing a stereogenic center in each structure, were determined by comparison of their experimental electronic circular dichroism (ECD) with those of calculated ECD values. PMID- 26678274 TI - Reliability generalization of the Texas Revised Inventory of Grief (TRIG). AB - While grief is a universal experience, this phenomenon is experienced in a variety of ways largely dependent upon one's cultural schema. To consider the potential problems inherent in generalizing the results of an assessment tool across cultures, this study explores the notion of generalizability in assessment by evaluating the reliability of the Texas Revised Inventory of Grief (TRIG) using a meta-analytic technique called reliability generalization. The TRIG demonstrated strong reliability with mean Cronbach's alphas of .90 and .82 for the present and past subscales, respectively. Overall, the TRIG, especially the present subscale, appears to produce reliable scores even across cultures. PMID- 26678269 TI - The Practice Guidelines for Primary Care of Acute Abdomen 2015. AB - BACKGROUND: Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines [all clinical questions (CQs) and recommendations are shown in supplementary information]. METHODS: A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. RESULTS: A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. CONCLUSIONS: The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen. PMID- 26678275 TI - Improving Wellbeing and Environmental Stewardship Through Volunteering in Nature. AB - Environmental volunteering (EV) can provide a unique way to optimise the wellbeing of participants while fostering environmental stewardship. However, the potential of EV to create human health benefits remains an under-researched area. This study provides evidence for improved wellbeing and mood state for 32 participants from diverse backgrounds undertaking EV activities. Most participants also reported improved environmental stewardship with a greatly improved understanding of the environment and the need to conserve it. Other benefits included: 31% of those seeking work obtained it; and 50% joined a volunteer group at program completion. EV provides a unique mechanism to enhance the wellbeing of the participants, while conserving the environment. PMID- 26678276 TI - Educational differences in disability retirement among young employees in Helsinki, Finland. AB - BACKGROUND: Disability retirement (DR) among young employees is an increasing problem affecting work life and public health, given the potential major loss of working time. Little is known about educational differences in the risk of DR among young employees, despite the need for such knowledge in targeting preventive measures. We examined the association between education and DR due to any cause and to mental and non-mental causes among young employees. METHODS: Personnel register data of the City of Helsinki from the years 2002-2013 for 25 to-34-year-old employees (n= 41225) were linked to register data from the Finnish Centre for Pensions on DR (n= 381), and from Statistics Finland on education. Education was categorised into four hierarchical groups. The mean follow-up time was 5.7 years. Cox regression analysis was used. RESULTS: There were 381 DR events and of the events, over 70% were due to mental disorders and 72% were temporary. A consistent educational gradient was found. Those with a basic education were at the highest risk of DR due to any cause (HR 4.64, 95% CI 3.07, 7.02), and to mental (HR 4.79, 95% CI 2.89, 7.94) and non-mental causes (HR 4.32, 95% CI 2.10, 8.91). CONCLUSIONS: DR due to any cause, and to mental and non mental causes, followed a clear educational gradient. Early intervention, treatment and rehabilitation with a view to maintaining work ability are needed among young employees, especially those with low education. Adapting working conditions to their health and work ability may also help to avoid premature exit from work. PMID- 26678277 TI - Electroencephalogram complexity analysis in children with attention deficit/hyperactivity disorder during a visual cognitive task. AB - OBJECTIVE: The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. METHOD: Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. RESULTS: The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. CONCLUSION: Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD. PMID- 26678278 TI - Pharmacotherapy of neuropathic pain: time to rewrite the rulebook? PMID- 26678279 TI - The Identification of a Novel HIV-1 CRF01_AE/B Recombinant Based on Near Full Length Genomic Analysis in Yunnan Province, China. AB - Recombination contributes substantially to the genetic diversity of HIV-1. Recently, many kinds of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified in China, especially in areas with multiple subtypes of HIV-1 circulating. Yunnan, which borders the "Golden triangle" region of South China, is an epicenter of HIV-1 infections in China. Multiple subtypes, including subtypes B, CRF01_AE, CRF07_BC, and CRF08_BC, were found epidemic in the area. Many URFs composed of subtypes B and C genomes were identified in Yunnan; however, CRF01_AE/B recombinant form is relatively rare. In this study, we identified a novel recombinant form of CRF01_AE/B, which was isolated from a heterosexual transmitted individual. The genomic structure of the strain is distinctly different from any previously reported URFs. Three CRF01_AE segments were inserted into the subtype B backbone genome. In the past few years, many kinds of URFs and CRFs have emerged and spread quickly in China, which implies that coinfection or super infection of more than one HIV-1 subtype might be common in China, especially in Yunnan. Therefore, more work is needed to monitor the appearance of URFs and survey the epidemiologic significance of the new recombination. PMID- 26678280 TI - Airway Vagal Neuroplasticity Associated with Respiratory Viral Infections. AB - Respiratory virus infections leads to coughing, sneezing, and increases in reflex parasympathetic bronchoconstriction and secretions. These responses to viral infection are exclusively or largely secondary to changes in the function of the nervous system. For many with underlying airway pathologies such as asthma and COPD, this neuroplasticity can lead to disease exacerbations and hospitalization. Relatively little is understood about the cellular and molecular mechanisms that underlie the changes in neuronal control of the respiratory tract during viral infection, but the evidence supports the idea that changes occur in the physiology of both the sensory and autonomic innervation. Virus infection can lead to acute increases in the activity of sensory nerves as well as to genetic changes causing alterations in sensory nerve phenotype. In addition, respiratory viral infections are associated with changes in the control of neurotransmitter release from cholinergic nerve endings terminating at the level of the airway smooth muscle. PMID- 26678281 TI - Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio). AB - AIM: We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. METHODS: Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. RESULTS: Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). CONCLUSION: Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity. PMID- 26678282 TI - Functioning and disability analysis by using WHO Disability Assessment Schedule 2.0 in older adults Taiwanese patients with dementia. AB - BACKGROUND: To analyse the disability status of elderly Taiwanese dementia patients by using the World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0). METHODS: We enrolled 12 126 disabled elderly (>65 years) patients with dementia during July 2012-January 2014 from the Taiwan Data Bank of Persons with Disability. Trained interviewers evaluated the standardised scores in the six WHODAS 2.0 domains. Student's t test was used for comparing WHODAS 2.0 scores of male and female dementia patients with different age groups. RESULTS: The study population comprised 12 126 patients; 7612 were women and 4514 were men. The WHODAS 2.0 scores showed that the dementia patients had global activity limitation and participation restriction in all domains. Dementia-induced disability was prominent in male patients in all of the domains of the WHODAS 2.0. The domains of life activities, getting along with people and cognition were more strongly affected than the other domains. However, women experienced more rapid functional decline than men did as they aged. CONCLUSION: The data analysed in this large-scale, population-based study revealed crucial information on dementia-induced disability in elderly patients on the basis of the WHODAS 2.0 framework. Implications for rehabilitation Dementia patients have global functional disability in all domains of WHODAS 2.0 and multidisciplinary team is needed for rehabilitation programme intervention for these patients. When considering the rehabilitation resource and strategy, the domains of cognition, activities of daily living and life activities should be focussed. When dementia patients aged 65-75 years old, male patients got more restriction of function than female and more medical resource allocation for disabled male patients is recommended. With ageing, female dementia patients exhibited more rapid functional decline than male patients did and more budget about rehabilitation for maintain functional and dementia progression is crucial for female patients. PMID- 26678283 TI - [Organ transplantation in Germany: Critical examination in times of scarce resources]. AB - Organ transplantation over the last 40 years has developed into a standardized successful procedure for the replacement of heart, kidney liver, lung, and pancreas. During this time, treatment strategies have greatly improved and novel procedures such as living related organ donation have been introduced. Despite these improvements, the number of organ transplants has stalled in recent years. In the face of increasing numbers of patients on the waiting list for organ transplantation, this situation is unacceptable and ways to improve the situation of organ transplantation have to be found.The reasons for the stagnant situation in organ transplantation are manifold and include lack of awareness in the general population, insufficient organ procurement in hospitals as well as problems in organ allocation. The criteria for organ allocation have been unfairly reported to EUROTRANSPLANT by some of the presently 44 centers in order of more rapidly receive an organ for their patients on the waiting list. The evolving discussions around this so-called transplantation scandal has further eroded support for organ transplantation in Germany. A critical assessment and a well-defined plan are necessary to improve the situation, increase the number of transplanted organs, and reduce the unacceptably long waiting time for patients in Germany. PMID- 26678285 TI - [Erratum to: Diagnosis and treatment of sarcoidosis. Current standards]. PMID- 26678284 TI - [Cancer and life style: What really helps?]. AB - The continuously growing number of patients who survive cancer (long-term survivors) and their special life situations necessitate an increasing need for consultation on the topics of quality of life and recurrence prophylaxis. This consultation is often associated with aspects of complementary medicine and also social medicine, which are becoming increasingly more important in the long-term care of patients. This article presents the scientifically proven knowledge on the aspects of nutrition, sport, nicotine abuse and professional rehabilitation and their importance for the course of cancer diseases. PMID- 26678287 TI - Automated identification of copepods using digital image processing and artificial neural network. AB - BACKGROUND: Copepods are planktonic organisms that play a major role in the marine food chain. Studying the community structure and abundance of copepods in relation to the environment is essential to evaluate their contribution to mangrove trophodynamics and coastal fisheries. The routine identification of copepods can be very technical, requiring taxonomic expertise, experience and much effort which can be very time-consuming. Hence, there is an urgent need to introduce novel methods and approaches to automate identification and classification of copepod specimens. This study aims to apply digital image processing and machine learning methods to build an automated identification and classification technique. RESULTS: We developed an automated technique to extract morphological features of copepods' specimen from captured images using digital image processing techniques. An Artificial Neural Network (ANN) was used to classify the copepod specimens from species Acartia spinicauda, Bestiolina similis, Oithona aruensis, Oithona dissimilis, Oithona simplex, Parvocalanus crassirostris, Tortanus barbatus and Tortanus forcipatus based on the extracted features. 60% of the dataset was used for a two-layer feed-forward network training and the remaining 40% was used as testing dataset for system evaluation. Our approach demonstrated an overall classification accuracy of 93.13% (100% for A. spinicauda, B. similis and O. aruensis, 95% for T. barbatus, 90% for O. dissimilis and P. crassirostris, 85% for O. similis and T. forcipatus). CONCLUSIONS: The methods presented in this study enable fast classification of copepods to the species level. Future studies should include more classes in the model, improving the selection of features, and reducing the time to capture the copepod images. PMID- 26678286 TI - Precise genotyping and recombination detection of Enterovirus. AB - Enteroviruses (EV) with different genotypes cause diverse infectious diseases in humans and mammals. A correct EV typing result is crucial for effective medical treatment and disease control; however, the emergence of novel viral strains has impaired the performance of available diagnostic tools. Here, we present a web based tool, named EVIDENCE (EnteroVirus In DEep conception, http://symbiont.iis.sinica.edu.tw/evidence), for EV genotyping and recombination detection. We introduce the idea of using mixed-ranking scores to evaluate the fitness of prototypes based on relatedness and on the genome regions of interest. Using phylogenetic methods, the most possible genotype is determined based on the closest neighbor among the selected references. To detect possible recombination events, EVIDENCE calculates the sequence distance and phylogenetic relationship among sequences of all sliding windows scanning over the whole genome. Detected recombination events are plotted in an interactive figure for viewing of fine details. In addition, all EV sequences available in GenBank were collected and revised using the latest classification and nomenclature of EV in EVIDENCE. These sequences are built into the database and are retrieved in an indexed catalog, or can be searched for by keywords or by sequence similarity. EVIDENCE is the first web-based tool containing pipelines for genotyping and recombination detection, with updated, built-in, and complete reference sequences to improve sensitivity and specificity. The use of EVIDENCE can accelerate genotype identification, aiding clinical diagnosis and enhancing our understanding of EV evolution. PMID- 26678289 TI - High School Athletes' Parents' Perceptions and Knowledge of the Skills and Job Requirements of the Certified Athletic Trainer. AB - CONTEXT: Parents play a crucial role in determining medical services for their children, and it is important they understand the scope of practice and skills of the athletic trainer (AT). OBJECTIVE: To understand parents' perceptions and knowledge of the skills and job requirements of the secondary school AT. DESIGN: Cross-sectional study. SETTING: Sport meetings and banquets at 5 high schools in southwest Michigan during the fall, winter, and spring seasons. PATIENTS OR OTHER PARTICIPANTS: A total of 539 parents whose children competed in at least 1 high school sport participated. DATA COLLECTION AND ANALYSIS: A Parents' Perceptions and Knowledge of Certified Athletic Trainers Survey consisting of 32 questions, divided into 3 sections (demographics, perceptions, and knowledge), was developed and given to parents of high school athletes. One-way analyses of variance were used to determine significance among 3 categories of experience and perception and knowledge of ATs. RESULTS: Of the 539 parents who responded, 28% responded yes, and 72% responded no to having experience with an AT for their own injuries. When asked if they had experience with an AT due to their child's injuries, 60% responded yes. We found a difference among the 3 categories of experience for perception scores (P = .002) and knowledge scores (P < .001). CONCLUSIONS: In the absence of past experience with an AT, parents' perceptions and knowledge of the skills and job requirements of the secondary school AT are limited. Athletic trainers should educate parents on their professional roles, which may enhance their ability to provide better health care. PMID- 26678288 TI - Necessity of Removing American Football Uniforms From Humans With Hyperthermia Before Cold-Water Immersion. AB - CONTEXT: The National Athletic Trainers' Association and the American College of Sports Medicine have recommended removing American football uniforms from athletes with exertional heat stroke before cold-water immersion (CWI) based on the assumption that the uniform impedes rectal temperature (T(rec)) cooling. Few experimental data exist to verify or disprove this assumption and the recommendations. OBJECTIVES: To compare CWI durations, T(rec) cooling rates, thermal sensation, intensity of environmental symptoms, and onset of shivering when hyperthermic participants wore football uniforms during CWI or removed the uniforms immediately before CWI. DESIGN: Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Eighteen hydrated, physically active men (age = 22 +/- 2 years, height = 182.5 +/- 6.1 cm, mass = 85.4 +/- 13.4 kg, body fat = 11% +/- 5%, body surface area = 2.1 +/- 0.2 m(2)) volunteered. INTERVENTION(S): On 2 days, participants exercised in the heat (approximately 40 degrees C, approximately 40% relative humidity) while wearing a full American football uniform (shoes; crew socks; undergarments; shorts; game pants; undershirt; shoulder pads; jersey; helmet; and padding over the thighs, knees, hips, and tailbone [PADS]) until T(rec) reached 39.5 degrees C. Next, participants immersed themselves in water that was approximately 10 degrees C while wearing either undergarments, shorts, and crew socks (NOpads) or PADS without shoes until Trec reached 38 degrees C. MAIN OUTCOME MEASURE(S): The CWI duration (minutes) and T(rec) cooling rates ( degrees C/min). RESULTS: Participants had similar exercise times (NOpads = 40.8 +/- 4.9 minutes, PADS = 43.2 +/- 4.1 minutes; t(17) = 2.0, P = .10), hypohydration levels (NOpads = 1.5% +/- 0.3%, PADS = 1.6% +/- 0.4%; t(17) = 1.3, P = .22), and thermal-sensation ratings (NOpads = 7.2 +/- 0.3, PADS = 7.1 +/- 0.5; P > .05) before CWI. The CWI duration (median [interquartile range]; NOpads = 6.0 [5.4] minutes, PADS = 7.3 [9.8] minutes; z = 2.3, P = .01) and T(rec) cooling rates (NOpads = 0.28 degrees C/min +/- 0.14 degrees C/min, PADS = 0.21 degrees C/min +/- 0.11 degrees C/min; t(17) = 2.2, P = .02) differed between uniform conditions. CONCLUSIONS: Whereas participants cooled faster in NOpads, we still considered the PADS cooling rate to be acceptable (ie, >0.16 degrees C/min). Therefore, if clinicians experience difficulty removing PADS or CWI treatment is delayed, they may immerse fully equipped hyperthermic football players in CWI and maintain acceptable T(rec) cooling rates. Otherwise, PADS should be removed preimmersion to ensure faster body core temperature cooling. PMID- 26678290 TI - Methods and Descriptive Epidemiology of Services Provided by Athletic Trainers in High Schools: The National Athletic Treatment, Injury and Outcomes Network Study. AB - CONTEXT: Research is limited on the extent and nature of the care provided by athletic trainers (ATs) to student-athletes in the high school setting. OBJECTIVE: To describe the methods of the National Athletic Treatment, Injury and Outcomes Network (NATION) project and provide the descriptive epidemiology of AT services for injury care in 27 high school sports. DESIGN: Descriptive epidemiology study. SETTING: Athletic training room (ATR) visits and AT services data collected in 147 high schools from 26 states. PATIENTS OR OTHER PARTICIPANTS: High school student-athletes participating in 13 boys' sports and 14 girls' sports during the 2011-2012 through 2013-2014 academic years. MAIN OUTCOME MEASURE(S): The number of ATR visits and individual AT services, as well as the mean number of ATR visits (per injury) and AT services (per injury and ATR visit) were calculated by sport and for time-loss (TL) and non-time-loss (NTL) injuries. RESULTS: Over the 3-year period, 210 773 ATR visits and 557 381 AT services were reported for 50 604 injuries. Most ATR visits (70%) were for NTL injuries. Common AT services were therapeutic activities or exercise (45.4%), modalities (18.6%), and AT evaluation and reevaluation (15.9%), with an average of 4.17 +/- 6.52 ATR visits and 11.01 +/- 22.86 AT services per injury. Compared with NTL injuries, patients with TL injuries accrued more ATR visits (7.76 versus 3.47; P < .001) and AT services (18.60 versus 9.56; P < .001) per injury. An average of 2.24 +/- 1.33 AT services were reported per ATR visit. Compared with TL injuries, NTL injuries had a larger average number of AT services per ATR visit (2.28 versus 2.05; P < .001). CONCLUSIONS: These findings highlight the broad spectrum of care provided by ATs to high school student-athletes and demonstrate that patients with NTL injuries require substantial amounts of AT services. PMID- 26678292 TI - Erratum to: Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation. PMID- 26678291 TI - False-Positive Rates of Reliable Change Indices for Concussion Test Batteries: A Monte Carlo Simulation. AB - BACKGROUND: Neurocognitive testing is widely performed for the assessment of concussion. Athletic trainers can use preseason baselines with reliable change indices (RCIs) to ascertain whether concussed athletes' cognitive abilities are below preinjury levels. Although the percentage of healthy individuals who show decline on any individual test is determined by its RCI's confidence level (eg, 10% false-positive rate using an RCI with an 80% confidence interval), the expected rate of 1 or more significant RCIs across multiple indices is unclear. OBJECTIVE: To use a Monte Carlo simulation procedure to estimate the normal rate (ie, base rate) of significant decline on 1 or more RCIs in multitest batteries. RESULTS & CONCLUSION: For batteries producing 7 or more uncorrelated RCIs (80% confidence intervals), the majority of normal individuals would show significant declines on at least 1 RCI. Expected rates are lower for tests with fewer indices, higher inter-RCI correlations, and more stringent impairment criteria. These reference points can help testers interpret RCI output for multitest batteries. PMID- 26678293 TI - Rabies in a Dog Imported from Egypt with a Falsified Rabies Vaccination Certificate--Virginia, 2015. AB - Canine rabies virus variant has been eliminated in the United States and multiple other countries. Globally, however, dogs remain the principal source for human rabies infections. The World Health Organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been subjected to a serologic test for rabies before shipment. On June 8, 2015, an adult female dog that had recently been picked up from the streets of Cairo, Egypt, and shipped by a U.S. animal rescue organization to the United States was confirmed to have rabies by the Virginia Department of General Services Division of Consolidated Laboratory Services (DCLS). This dog was part of a large shipment of dogs and cats from Egypt that rescue organizations had distributed to multiple states for adoption. During the investigation, public health officials learned that the rabies vaccination certificate used for entry of the rabid dog into the United States had intentionally been falsified to avoid exclusion of the dog from entry under CDC's current dog importation regulations. This report underscores the ongoing risk posed by U.S. importation of domestic animals that have not been adequately vaccinated against rabies. PMID- 26678294 TI - "Why Didn't it Work?" Lessons From a Randomized Controlled Trial of a Web-based Personally Controlled Health Management System for Adults with Asthma. AB - BACKGROUND: Personally controlled health management systems (PCHMS), which may include a personal health record (PHR), health management tools, and information resources, have been advocated as a next-generation technology to improve health behaviors and outcomes. There have been successful trials of PCHMS in various health settings. However, there is mixed evidence for whether consumers will use these systems over the long term and whether they ultimately lead to improved health outcomes and behaviors. OBJECTIVE: The aim was to test whether use of a PCHMS by consumers can increase the uptake or updating of a written asthma action plan (AAP) among adults with asthma. METHODS: A 12-month parallel 2-group randomized controlled trial was conducted. Participants living with asthma were recruited nationally in Australia between April and August 2013, and randomized 1:1 to either the PCHMS group or control group (online static educational content). The primary outcome measure was possession of an up-to-date written AAP poststudy. Secondary measures included (1) utilizing the AAP; (2) planned or unplanned visits to a health care professional for asthma-related concerns; (3) severe asthma exacerbation, inadequately controlled asthma, or worsening of asthma that required a change in treatment; and (4) number of days lost from work or study due to asthma. Ancillary analyses examined reasons for adoption or nonadoption of the intervention. Outcome measures were collected by online questionnaire prestudy, monthly, and poststudy. RESULTS: A total of 330 eligible participants were randomized into 1 of 2 arms (intervention: n=154; control: n=176). Access to the PCHMS was not associated with a significant difference in any of the primary or secondary outcomes. Most participants (80.5%, 124/154) did not access the intervention or accessed it only once. CONCLUSIONS: Despite the intervention being effective in other preventive care settings, system use was negligible and outcome changes were not seen as a result. Consumers must perceive the need for assistance with a task and assign priority to the task supported by the eHealth intervention. Additionally, the cost of adopting the intervention (eg, additional effort, time spent learning the new system) must be lower than the benefit. Otherwise, there is high risk consumers will not adopt the eHealth intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000716864; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362714 (Archived by WebCite(r) at http://www.webcitation.org/6dMV6hg4A). PMID- 26678295 TI - Fentanyl bolus induces muscle tremors in sevoflurane-anaesthetized piglets. AB - Intravenous fentanyl (10 mcg/kg) or saline (control) was randomly administered to 10 healthy sevoflurane-mono-anaesthetized piglets. Trembling was assessed by two blinded observers using a visual analogue scale (VAS) and a simple ordinal scale at baseline and 5 min (T5) after drug administration. If no trembling was observed at that time point, the opposite treatment was administered and piglets were re-evaluated after another 5 min (T10). Four out of five piglets showed trembling after fentanyl (T5), while none given saline showed any trembling. With fentanyl the VAS scores were significantly higher at T5 compared either with baseline or with the control treatment. Control animals received fentanyl after the 5 min evaluation and all piglets showed clear trembling afterwards. The median time after fentanyl administration until first muscle tremors was 51 (20 840) s. In summary, nine out of 10 sevoflurane-anaesthetized piglets showed muscle tremors after intravenous fentanyl. Tremors subsided over time and no specific treatment was necessary. PMID- 26678296 TI - Detection of antibodies against Theiler's murine encephalomyelitis virus GDVII strain in experimental guinea pigs. AB - A disease affecting guinea pigs called 'guinea pig lameness' characterized by clinical signs of depression, lameness of limbs, flaccid paralysis, weight loss and death within a few weeks was first described by Romer in 1911. After a research group in our facility kept laboratory guinea pigs from two different origins together in one room, lameness was observed in two animals. Further investigations revealed a serological immune response against Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) in these animals. Histopathology of the lumbar spinal cord of these animals showed mononuclear cell infiltration and necrotic neurons in the anterior horn. Therefore, all guinea pigs from this contaminated animal unit, from other units in our facility, as well as from different European institutions and breeding centres were screened for antibodies directed against GDVII. Our investigations showed that approximately 80% of all guinea pigs from the contaminated animal unit were seropositive for GDVII, whereas animals from other separate units were completely negative. In addition, 43% of tested sera from the different European institutions and breeding centres contained antibodies against GDVII. The present data confirm that an unknown viral infection causes an immune response in experimental guinea pigs leading to seroconversion against GDVII and that guinea pigs from a commercial breeder are the source of the infection. PMID- 26678297 TI - A novel postoperative immobilization model for murine Achilles tendon sutures. AB - The body's motion and function are all in part effected by a vital tissue, the tendon. Tendon injury often results in limited functioning after postoperative procedures and even for a long time after rehabilitation. Although numerous studies have reported surgical procedures using animal models which have contributed to both basic and clinical research, modeling of tendon sutures or postoperative immobilizations has not been performed on small experimental animals, such as mice. In this study we have developed an easy Achilles tendon suture and postoperative ankle fixation model in a mouse. Right Achilles tendons were incised and 10-0 nylons were passed through the proximal and distal ends using a modified Kessler method. Subsequently, the right ankle was immobilized in a plantarflexed position with novel splints, which were made from readily available extension tubes. Restriction of the tendon using handmade splints reduced swelling, as opposed to fixating with the usual plaster of Paris. Using this method, the usage of the right Achilles tendons began on postoperative days 13.5 +/- 4.6, which indicated healing within two weeks. Therefore our simple short-term murine Achilles tendon suture procedure is useful for studying immediate tendon repair mechanisms in various models, including genetically modified mice. PMID- 26678298 TI - The realization of the dipole (gamma, gamma) method and its application to determine the absolute optical oscillator strengths of helium. AB - The dipole (gamma, gamma) method, which is the inelastic x-ray scattering operated at a negligibly small momentum transfer, is proposed and realized to determine the absolute optical oscillator strengths of the vanlence-shell excitations of atoms and molecules. Compared with the conventionally used photoabsorption method, this new method is free from the line saturation effect, which can seriously limit the accuracies of the measured photoabsorption cross sections for discrete transitions with narrow natural linewidths. Furthermore, the Bethe-Born conversion factor of the dipole (gamma, gamma) method varies much more slowly with the excitation energy than does that of the dipole (e, e) method. Absolute optical oscillator strengths for the excitations of 1s(2) -> 1 snp(n = 3-7) of atomic helium have been determined using the high-resolution dipole (gamma, gamma) method, and the excellent agreement of the present measurements with both those measured by the dipole (e, e) method and the previous theoretical calculations indicates that the dipole (gamma, gamma) method is a powerful tool to measure the absolute optical oscillator strengths of the valence-shell excitations of atoms and molecules. PMID- 26678299 TI - Individualized Map of White Matter Pathways: Connectivity-Based Paradigm for Neurosurgical Planning. AB - BACKGROUND: Advances in white matter tractography enhance neurosurgical planning and glioma resection, but white matter tractography is limited by biological variables such as edema, mass effect, and tract infiltration or selection biases related to regions of interest or fractional anisotropy values. OBJECTIVE: To provide an automated tract identification paradigm that corrects for artifacts created by tumor edema and infiltration and provides a consistent, accurate method of fiber bundle identification. METHODS: An automated tract identification paradigm was developed and evaluated for glioma surgery. A fiber bundle atlas was generated from 6 healthy participants. Fibers of a test set (including 3 healthy participants and 10 patients with brain tumors) were clustered adaptively with this atlas. Reliability of the identified tracts in both groups was assessed by comparison with 2 experts with the Cohen kappa used to quantify concurrence. We evaluated 6 major fiber bundles: cingulum bundle, fornix, uncinate fasciculus, arcuate fasciculus, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus, the last 3 tracts mediating language function. RESULTS: The automated paradigm demonstrated a reliable and practical method to identify white mater tracts, despite mass effect, edema, and tract infiltration. When the tumor demonstrated significant mass effect or shift, the automated approach was useful for providing an initialization to guide the expert with identification of the specific tract of interest. CONCLUSION: We report a reliable paradigm for the automated identification of white matter pathways in patients with gliomas. This approach should enhance the neurosurgical objective of maximal safe resections. ABBREVIATIONS: AF, arcuate fasciculusDTI, diffusion tensor imagingIFOF, inferior fronto-occipital fasciculusILF, inferior longitudinal fasciculusROI, region of interestWM, white matter. PMID- 26678301 TI - Red emission generation through highly efficient energy transfer from Ce(3+) to Mn(2+) in CaO for warm white LEDs. AB - CaO:Ce(3+),Mn(2+) phosphors with various Mn(2+) concentrations were synthesized by a solid state reaction method. Efficient energy transfer from Ce(3+) to Mn(2+) was observed and it allows the emission color of CaO:Ce(3+),Mn(2+) to be continuously tuned from yellow (contributed by Ce(3+)) to red (by Mn(2+)) with an increase in Mn(2+) concentration and upon blue light excitation. The red emission becomes dominant when the Mn(2+) concentration is >=0.014 with an energy transfer efficiency higher than 87% which can reach as high as 94% for a Mn(2+) concentration of only 0.02. A critical distance of 10.5 A for the Ce(3+)-Mn(2+) energy transfer was determined. A faster decrease of Ce(3+) luminescence intensity in comparison with its lifetime was observed on increasing the Mn(2+) concentration. The analysis of this feature reveals that the Ce(3+) excitation energy can be completely transferred to Mn(2+) if the Ce(3+)-Mn(2+) distance is shorter than 7.6 A. A warm white LED was fabricated through integrating an InGaN blue LED chip and a blend of two phosphors (YAG:Ce(3+) yellow phosphor and CaO:0.007Ce(3+),0.014Mn(2+) red phosphor) into a single package, which has CIE chromaticity coordinates of (x = 0.37, y = 0.35), a correlated color temperature of 3973 K and a color rendering index of 83.1. The results indicate that CaO:Ce(3+),Mn(2+) may serve as a potential red phosphor for blue LED based warm white LEDs. PMID- 26678300 TI - Ultrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivo. AB - Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72 mm-long artery in 4 seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions. PMID- 26678302 TI - Prevention of dental accidents in Swiss boxing clubs. AB - Boxing involves a high risk of dental trauma due to the impact of enormous external forces against the head. Wearing a mouthguard is, therefore, mandatory. The aim of this study was to evaluate the prevalence of dental trauma as well as the utilization and quality of mouthguards in Swiss boxing clubs. In order to achieve this, data on the mouthguards of 217 boxers in total were collected using questionnaires and examination forms, which were statistically evaluated. Out of the 217 boxers, 75 (34.6%) had already experienced a dental accident, but only 8 (10.7%) of them while practicing their sport. Professional boxers were most frequently affected by dental trauma (p = 0.001). Crown fractures were most often observed, followed by tooth dislocations. All interviewed athletes owned a mouthguard, which they used much more consistently during full-contact sparring (practice fighting) than during regular partner exercises. Most of the boxers used prefabricated mouthguards, which could be individually adapted using the ?boil and bite? system. The majority of the athletes received their mouthguards from the boxing club. Impaired speaking when wearing a mouthguard was, by far, the problem most frequently mentioned by the athletes. In terms of these bothering factors, custom-made mouthguards from dentists received the best rating (p = 0.002). The quality of the mouthguard was assessed by evaluating the following criteria: coverage of the buccolabial surface, occlusal support of the opposing dentition, thickness of the occlusal layer, and rounded edges. Of the 215 mouthguards examined, 193 (89.8%) were insufficient (p = 0.002). Despite the observed deficiencies, only a few dental injuries occurred during boxing. This study shows that although basic preventive measures do exist in Swiss boxing, they should be improved substantially by providing better instruction and more information. PMID- 26678303 TI - Microbial properties explain temporal variation in soil respiration in a grassland subjected to nitrogen addition. AB - The role of soil microbial variables in shaping the temporal variability of soil respiration has been well acknowledged but is poorly understood, particularly under elevated nitrogen (N) deposition conditions. We measured soil respiration along with soil microbial properties during the early, middle, and late growing seasons in temperate grassland plots that had been treated with N additions of 0, 2, 4, 8, 16, or 32 g N m(-2) yr(-1) for 10 years. Representing the averages over three observation periods, total (Rs) and heterotrophic (Rh) respiration were highest with 4 g N m(-2) yr(-1), but autotrophic respiration (Ra) was highest with 8 to 16 g N m(-2) yr(-1). Also, the responses of Rh and Ra were unsynchronized considering the periods separately. N addition had no significant impact on the temperature sensitivity (Q10) for Rs but inhibited the Q10 for Rh. Significant interactions between observation period and N level occurred in soil respiration components, and the temporal variations in soil respiration components were mostly associated with changes in microbial biomass carbon (MBC) and phospholipid fatty acids (PLFAs). Further observation on soil organic carbon and root biomass is needed to reveal the long-term effect of N deposition on soil C sequestration. PMID- 26678304 TI - Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults. AB - Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18-76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID- 26678305 TI - Evaluation of the mechanisms of intron loss and gain in the social amoebae Dictyostelium. AB - BACKGROUND: Spliceosomal introns are a common feature of eukaryotic genomes. To approach a comprehensive understanding of intron evolution on Earth, studies should look beyond repeatedly studied groups such as animals, plants, and fungi. The slime mold Dictyostelium belongs to a supergroup of eukaryotes not covered in previous studies. RESULTS: We found 441 precise intron losses in Dictyostelium discoideum and 202 precise intron losses in Dictyostelium purpureum. Consistent with these observations, Dictyostelium discoideum was found to have significantly more copies of reverse transcriptase genes than Dictyostelium purpureum. We also found that the lost introns are significantly further from the 5' end of genes than the conserved introns. Adjacent introns were prone to be lost simultaneously in Dictyostelium discoideum. In both Dictyostelium species, the exonic sequences flanking lost introns were found to have a significantly higher GC content than those flanking conserved introns. Together, these observations support a reverse transcription model of intron loss in which intron losses were caused by gene conversion between genomic DNA and cDNA reverse transcribed from mature mRNA. We also identified two imprecise intron losses in Dictyostelium discoideum that may have resulted from genomic deletions. Ninety-eight putative intron gains were also observed. Consistent with previous studies of other lineages, the source sequences were found in only a small number of cases, with only two instances of intron gain identified in Dictyostelium discoideum. CONCLUSIONS: Although they diverged very early from animals and fungi, Dictyostelium species have similar mechanisms of intron loss. PMID- 26678307 TI - Serotonergic neurons derived from induced pluripotent stem cells (iPSCs): a new pathway for research on the biology and pharmacology of major depression. PMID- 26678306 TI - The Incidence of Postoperative Endophthalmitis Before and After a Revised Preoperative Surgical Site Preparation Protocol. AB - PURPOSE: To compare the incidence of postoperative endophthalmitis before and after the implementation of a preoperative surgical site preparation protocol for cataract surgery. DESIGN: Retrospective cohort study. METHODS: Records of patients with postoperative endophthalmitis between January 2006 and August 2013 were reviewed. A revised protocol implemented after January 2009 included the addition of preoperative 0.3% topical tobramycin, 10% povidone-iodine for cleansing, and using a disposable sterile drape. The incidence, microbiological profile, and outcomes of these cases were analyzed. RESULTS: The incidence of preprotocol endophthalmitis was significantly higher than in the postprotocol period (P = 0.018). More patients in the preprotocol group grew Pseudomonas aeruginosa and Streptococcus pneumoniae as compared with those in the postprotocol group (P = 0.014). A smaller number of patients attained a poor visual outcome after the implementation of the revised protocol (P = 0.035). CONCLUSIONS: In our study, the addition of antibiotic eye drops before cataract surgery and perioperative cleansing with 10% povidone-iodine were effective means to reduce the incidence of postoperative endophthalmitis. PMID- 26678308 TI - The different moods of human serotonergic neurons. PMID- 26678309 TI - Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution. AB - BACKGROUND: Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet. METHODS: eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. RESULTS: Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet. CONCLUSIONS: A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow. PMID- 26678310 TI - Bioinformatical parsing of folding-on-binding proteins reveals their compositional and evolutionary sequence design. AB - Intrinsic disorder occurs when (part of) a protein remains unfolded during normal functioning. Intrinsically-disordered regions can contain segments that 'fold on binding' to another molecule. Here, we perform bioinformatical parsing of human 'folding-on-binding' (FB) proteins, into four subsets: Ordered regions, FB regions, Disordered regions that surround FB regions ('Disordered-around-FB'), and Other-Disordered regions. We examined the composition and evolutionary behaviour (across vertebrate orthologs) of these subsets. From a convergence of three separate analyses, we find that for hydrophobicity, Ordered regions segregate from the other subsets, but the Ordered and FB regions group together as highly conserved, and the Disordered-around-FB and Other-Disordered regions as less conserved (with a lesser significant difference between Ordered and FB regions). FB regions are highly-conserved with net positive charge, whereas Disordered-around-FB have net negative charge and are relatively less hydrophobic than FB regions. Indeed, these Disordered-around-FB regions are excessively hydrophilic compared to other disordered regions generally. We describe how our results point towards a possible compositionally-based steering mechanism of folding-on-binding. PMID- 26678311 TI - Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides. AB - INTRODUCTION: Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS. METHODS: We followed prospectively 21 patients (stages IB IV): 15 with early stage MF and 6 with advanced disease. "Mini" and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS). RESULTS: After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades. CONCLUSIONS: We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA. PMID- 26678312 TI - Evaluation of a simple intervention to reduce exchange transfusion rates among inborn and outborn neonates in Myanmar, comparing pre- and post-intervention rates. AB - BACKGROUND: In Myanmar, approximately half of all neonatal hospital admissions are for hyperbilirubinaemia, and tertiary facilities report high rates of Exchange Transfusion (ET). The aim of this study was to evaluate the effectiveness of the pilot program in reducing ET, separately of inborn and outborn neonates. METHODS: The study was conducted in the Neonatal Care Units of four national tertiary hospitals: two exclusively treating inborn neonates, and two solely for outborn neonates. Prior to intervention, no high intensity phototherapy was available in these units. Intervention in late November 2011 comprised, for each hospital, provision of two high intensity LED phototherapy machines, a photo radiometer, and training of personnel. Hospital-specific data were assessed as Relative Risk (RR) ratios comparing ET rates pre- and post intervention, and individual hospital results were pooled when appropriate. RESULTS: In 2011, there were 118 ETs among inborn neonates and 140 ETs among outborn neonates. The ET rate was unchanged at Inborn Hospital A (RR = 1.07; 95 % CI: 0.80-1.43; p = 0.67), and reduced by 69 % at Inborn Hospital B (RR = 0.31; 95 % CI: 0.17-0.57; p < 0.0001). For outborn neonates, the pooled estimate indicated that ET rates reduced by 33 % post-intervention (RRMH = 0.67; 95 % CI: 0.52-0.87; p = 0.002); heterogeneity was not a problem. CONCLUSION: Together with a photoradiometer and education, intensive phototherapy can significantly reduce the ET rate. Inborn Hospital A had four times as many admissions for jaundice as Inborn Hospital B, and did not reduce ET until it received additional high intensity machines. The results highlight the importance of providing enough intensive phototherapy units to treat all neonates requiring high intensity treatment for a full course. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001171505 , 2 November 2015. PMID- 26678313 TI - Neuroblastoma: As a matter of FACT. PMID- 26678318 TI - Streptococcus equi Detection Polymerase Chain Reaction Assay for Equine Nasopharyngeal and Guttural Pouch Wash Samples. AB - BACKGROUND: Bacterial culture and polymerase chain reaction (PCR) assays for the detection of Streptococcus equi in nasopharyngeal washes (NPW) and guttural pouch lavage (GPL) samples have low sensitivity. In human diagnostics, processing of samples with flocked swabs has improved recovery rates of bacterial agents because of improved surface area and elution factors. HYPOTHESIS: For S. equi subsp. equi (S. equi) detection in NPW and GPL samples we hypothesized that: direct-PCR would be more reliable than flocked swab culture (FS culture); flocked swab PCR (FS-PCR) would be equivalent to direct-PCR; and FS culture would be more reliable than traditional culture. SAMPLES: A total of 193 samples (134 NPW and 59 GPL) from 113 horses with either suspected S. equi infection, convalescing from a known S. equi infection, or asymptomatic horses screened for S. equi. METHODS: Prospective study. Samples were submitted for S. equi direct-PCR. Using logistic regression, direct-PCR (gold standard) was compared to FS culture, traditional culture, and FS-PCR also performed. RESULTS: Direct-PCR was statistically more sensitive than FS-PCR, FS culture, and traditional culture (P < .001). All methods had sensitivities <70% relative to the direct-PCR. FS culture had a similar sensitivity relative to traditional culture. The odds of GPL samples being positive on direct-PCR (P = .030) and FS-PCR were greater than those for NPW samples (P = .021). CONCLUSIONS AND CLINICAL IMPORTANCE: Use of flocked swabs during laboratory preprocessing did not improve detection of S. equi via either PCR or bacterial culture from samples. Direct-PCR is the preferred method of detection of S. equi. PMID- 26678319 TI - Feasibility of Echocardiographic Techniques to Detect Subclinical Cancer Therapeutics-Related Cardiac Dysfunction among High-Dose Patients When Compared with Cardiac Magnetic Resonance Imaging. AB - BACKGROUND: Cardiac magnetic resonance imaging (CMR) is the gold standard for the quantification of global and regional myocardial function and can detect subclinical myocardial dysfunction in anthracycline-induced cardiomyopathy. The aim of this study was to ascertain reliable echocardiographic parameters that can be used for the early identification of cancer therapeutics-related cardiac dysfunction, compared with CMR. METHODS: Fifty-seven pediatric cancer survivors, 10 to 42 years of age, with cumulative anthracycline doses >= 200 mg/m(2), were studied with transthoracic echocardiography and CMR 2.4 to 26.9 years after chemotherapy. RESULTS: Three-dimensional echocardiography had the highest sensitivity in identifying subjects with CMR-derived ejection fractions < 55%. Subjects with end-systolic volume index values > 29 mL/m(2) were more likely to have CMR-derived ejection fractions < 55%. Three-dimensional speckle-tracking echocardiographic peak global longitudinal strain magnitude < -17.5% best identified subjects with abnormal peak midwall longitudinal strain magnitude by CMR. A decrease in early atrial myocardial velocity of <10 cm/sec at the interventricular septum also identified subjects with lower average peak midwall longitudinal strain and peak midwall circumferential strain magnitudes by CMR. CONCLUSIONS: Three-dimensional echocardiographic ejection fraction < 55%, end systolic volume index > 29 mL/m(2), three-dimensional speckle-tracking echocardiographic peak global longitudinal strain magnitude < -17.5%, and a decrease in early atrial myocardial velocity at the interventricular septum of <10 cm/sec by Doppler tissue imaging are the most sensitive transthoracic echocardiographic parameters to identify subjects with subclinical myocardial dysfunction by CMR. PMID- 26678314 TI - DNA damage and the balance between survival and death in cancer biology. AB - DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage. PMID- 26678320 TI - Infection and inflammation in induced sputum from preschool children with chronic airways diseases. AB - BACKGROUND: We hypothesized airway inflammation can be detected non-invasively by induced sputum (IS) or peripheral blood eosinophilia, and IS can detect bacterial and viral infection in preschool children with airway disease, with results comparable to broncho-alveolar lavage (BAL). METHODS: Preschool children with cystic fibrosis, recurrent wheeze, or wet cough underwent IS with nebulized hypertonic saline, chest physiotherapy, and oropharyngeal suction. Samples were analyzed for inflammation by cytology and bacterial culture, viral detection by PCR. Results were compared to BAL and blood in a sub-group undergoing clinically indicated bronchoscopy. RESULTS: 64 children (median age 33 [7-76] months) underwent IS without adverse events. IS was obtained from 61/64. Twenty out of sixty-four underwent BAL and IS, no IS was obtained in 2/23. Thirteen out of twenty-one (62%) had matching bacteria and viruses, 4/21 had positive BAL bacterial growth with negative IS, and 3/21 had negative BAL growth with positive IS. 67% of sputum samples were processed for cytology, 46% had <80% squamous cells; the proportion of squamous cells reduced with increasing age (r = -0.55, P < 0.01). IS was significantly more neutrophilic and less eosinophilic than BAL; 2/21 IS samples contained eosinophils compared to 17/23 BAL. There was a positive correlation between blood and BAL eosinophilia (r = 0.75, P < 0.01). CONCLUSION: IS from preschool children can be used to assess infection. BAL and IS culture concurred in approximately two-thirds. However, inflammation was measureable in only one-third of IS samples and the cell differential was predominantly neutrophilic compared to BAL. Blood eosinophils may provide a better reflection of lower airway eosinophilia in this age group. Pediatr Pulmonol. 2016;51:778 786. (c) 2015 WileyPeriodicals, Inc. PMID- 26678321 TI - RNA-based methods in virology. PMID- 26678315 TI - Somatic mosaicism: on the road to cancer. AB - Diversity is the basis of fitness selection. Although the genome of an individual is considered to be largely stable, there is theoretical and experimental evidence--both in model organisms and in humans--that genetic mosaicism is the rule rather than the exception. The continuous generation of cell variants, their interactions and selective pressures lead to life-long tissue dynamics. Individuals may thus enjoy 'clonal health', defined as a clonal composition that supports healthy morphology and physiology, or suffer from clonal configurations that promote disease, such as cancer. The contribution of mosaicism to these processes starts during embryonic development. In this Opinion article, we argue that the road to cancer might begin during these early stages. PMID- 26678322 TI - Eucommicin A, a beta-truxinate lignan from Eucommia ulmoides, is a selective inhibitor of cancer stem cells. AB - Cancer stem cells (CSCs) constitute a small population of undifferentiated cells within a tumor that have the ability to self-renew and drive tumor formation, thus behaving as cancer-initiating cancer cells. Therapeutic interventions that eliminate CSCs are necessary to completely cure patients, since CSCs are a crucial source of tumor recurrence and metastasis. An induced CSC-like (iCSCL) model was recently established using induced pluripotent stem cells (iPSCs). In this study, a natural product-eucommicin A-was identified from Eucommia ulmoides leaves by screening for anti-CSC activity using the iCSCL model. Its structure was elucidated by spectroscopic methods as a quinic acid diester of 3,4,3',4' tetrahydroxy-beta-truxinic acid. Eucommicin A exhibited selective anti-CSC activity and inhibited tumor sphere formation by iCSCL cells. The results of this study suggest that eucommicin A could serve as a lead compound in the development of drugs to abrogate the stemness and self-renewal ability of CSCs. PMID- 26678323 TI - The chloroplast membrane associated ceQORH putative quinone oxidoreductase reduces long-chain, stress-related oxidized lipids. AB - Under oxidative stress conditions the lipid constituents of cells can undergo oxidation whose frequent consequence is the production of highly reactive alpha,beta-unsaturated carbonyls. These molecules are toxic because they can add to biomolecules (such as proteins and nucleic acids) and several enzyme activities cooperate to eliminate these reactive electrophile species. CeQORH (chloroplast envelope Quinone Oxidoreductase Homolog, At4g13010) is associated with the inner membrane of the chloroplast envelope and imported into the organelle by an alternative import pathway. In the present study, we show that the recombinant ceQORH exhibits the activity of a NADPH-dependent alpha,beta unsaturated oxoene reductase reducing the double bond of medium-chain (C?9) to long-chain (18 carbon atoms) reactive electrophile species deriving from poly unsaturated fatty acid peroxides. The best substrates of ceQORH are 13 lipoxygenase-derived gamma-ketols. gamma-Ketols are spontaneously produced in the chloroplast from the unstable allene oxide formed in the biochemical pathway leading to 12-oxo-phytodienoic acid, a precursor of the defense hormone jasmonate. In chloroplasts, ceQORH could detoxify 13-lipoxygenase-derived gamma ketols at their production sites in the membranes. This finding opens new routes toward the understanding of gamma-ketols role and detoxification. PMID- 26678325 TI - Electromagnetic interference in intraoperative monitoring of motor evoked potentials and a wireless solution. AB - Intraoperative neurophysiological monitoring (IONM) is utilized to minimize neurological morbidity during spine surgery. Transcranial motor evoked potentials (TcMEPs) are principal IONM signals in which the motor cortex of the subject is stimulated with electrical pulses and the evoked potentials are recorded from the muscles of interest. Currently available monitoring systems require the connection of 40-60 lengthy lead wires to the patient. These wires contribute to a crowded and cluttered surgical environment, and limit the maneuverability of the surgical team. In this work, it was demonstrated that the cumbersome wired system is vulnerable to electromagnetic interference (EMI) produced by operating room (OR) equipment. It was hypothesized that eliminating the lengthy recording wires can remove the EMI induced in the IONM signals. Hence, a wireless system to acquire TcMEPs was developed and validated through bench-top and animal experiments. Side-by-side TcMEPs acquisition from the wired and wireless systems in animal experiments under controlled conditions (absence of EMI from OR equipment) showed comparable magnitudes and waveforms, thus demonstrating the fidelity in the signal acquisition of the wireless solution. The robustness of the wireless system to minimize EMI was compared with a wired-system under identical conditions. Unlike the wired-system, the wireless system was not influenced by the electromagnetic waves from the C-Arm X-ray machine and temperature management system in the OR. PMID- 26678326 TI - Effects of wound dressings on cultured primary keratinocytes. AB - Autologous cell-spray grafting of non-cultured epidermal cells is an innovative approach for the treatment of severe second-degree burns. After treatment, wounds are covered with dressings that are widely used in wound care management; however, little is known about the effects of wound dressings on individually isolated cells. The sprayed cells have to actively attach, spread, proliferate, and migrate in the wound for successful re-epithelialization, during the healing process. It is expected that exposure to wound dressing material might interfere with cell survival, attachment, and expansion. Two experiments were performed to determine whether some dressing materials have a negative impact during the early phases of wound healing. In one experiment, freshly isolated cells were seeded and cultured for one week in combination with eight different wound dressings used during burn care. Cells, which were seeded and cultured with samples of Adaptic((r)), Xeroform((r)), EZ Derm((r)), and Mepilex((r)) did not attach, nor did they survive during the first week. Mepitel((r)), N-Terface((r)), Polyskin((r)), and Biobrane((r)) dressing samples had no negative effect on cell attachment and cell growth when compared to the controls. In a second experiment, the same dressings were exposed to pre-cultured cells in order to exclude the effects of attachment and spreading. The results confirm the above findings. This study could be of interest for establishing skin cell grafting therapies in burn medicine and also for wound care in general. PMID- 26678328 TI - Vitamin D, PTH and the risk of overall and disease-specific mortality: Results of the Longitudinal Aging Study Amsterdam. AB - Observational studies suggest that low concentrations of serum 25-hydroxyvitamin D (25(OH)D) and high concentrations of parathyroid hormone (PTH) are associated with a higher risk of mortality. The aim of this study was to examine whether 25(OH)D and PTH concentrations are independently associated with overall and disease-specific (cardiovascular and cancer-related) mortality in a large, prospective population-based cohort of older adults. Data from 1317 men and women (65-85 years) of the Longitudinal Aging Study Amsterdam were used. Cox proportional hazard analyses were used to examine whether 25(OH)D and PTH at baseline were associated with overall mortality (with a follow-up of 18 years) and disease-specific mortality (with a follow-up of 13 years). Compared to persons in the reference category of >=75nmol/L, persons with serum 25(OH)D <25nmol/L (HR 1.46; 95% CI: 1.12-1.91) and 25-49.9nmol/L (HR 1.24; 95% CI: 1.01 1.53) had a significantly higher risk of overall mortality, as well as men with baseline PTH concentrations >=7pmol/L (HR 2.54 (95% CI: 1.58-4.08)), compared to the reference category of <2.33pmol/L. The relationship of 25(OH)D with overall mortality was partly mediated by PTH. Furthermore, men with PTH concentrations of >=7pmol/L (HR 3.22; 95% CI: 1.40-7.42) had a higher risk of cardiovascular mortality, compared to the reference category. No significant associations of 25(OH)D or PTH with cancer-related mortality were observed. Both 25(OH)D and PTH should be considered as important health markers. PMID- 26678327 TI - Identifying representative drug resistant mutants of HIV. AB - BACKGROUND: Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. RESULTS: In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. CONCLUSION: This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID- 26678329 TI - Essential tremor. AB - INTRODUCTION: Essential tremor is one of the most common movement disorders in the world, with prevalence in the general population of 0.4% to 3.9%. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of drug treatments in people with essential tremor of the hand? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 56 studies. After deduplication and removal of conference abstracts, 31 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 18 studies and the further review of 13 full publications. Of the 13 full articles evaluated, two RCTs were added at this update. We performed a GRADE evaluation for 11 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 13 interventions based on information about the effectiveness and safety of alprazolam, beta-blockers other than propranolol, botulinum A toxin-haemagglutinin complex, clonazepam, diazepam, gabapentin, levetiracetam, lorazepam, phenobarbital, primidone, propranolol, sodium oxybate, and topiramate. PMID- 26678330 TI - Climate change, nutrition and immunity: Effects of elevated CO2 and temperature on the immune function of an insect herbivore. AB - Balanced nutrition is fundamental to health and immunity. For herbivorous insects, nutrient-compositional shifts in host plants due to elevated atmospheric CO2 concentrations and temperature may compromise this balance. Therefore, understanding their immune responses to such shifts is vital if we are to predict the outcomes of climate change for plant-herbivore-parasitoid and pathogen interactions. We tested the immune response of Paropsis atomaria Olivier (Coleoptera: Chrysomelidae) feeding on Eucalyptus tereticornis Sm. seedlings exposed to elevated CO2 (640 MUmol mol(-1); CE) and temperature (ambient plus 4 degrees C; TE). Larvae were immune-challenged with a nylon monofilament in order to simulate parasitoid or pathogen attack without other effects of actual parasitism or pathology. The cellular (in vivo melanisation) and humoral (in vitro phenoloxidase PO activity) immune responses were assessed, and linked to changes in leaf chemistry. CE reduced foliar nitrogen (N) concentrations and increased C:N ratios and concentrations of total phenolics. The humoral response was reduced at CE. PO activity and haemolymph protein concentrations decreased at CE, while haemolymph protein concentrations were positively correlated with foliar N concentrations. However, the cellular response increased at CE and this was not correlated with any foliar traits. Immune parameters were not impacted by TE. Our study revealed that opposite cellular and humoral immune responses occurred as a result of plant-mediated effects at CE. In contrast, elevated temperatures within the tested range had minimal impact on immune responses. These complex interactions may alter the outcomes of parasitoid and pathogen attack in future climates. PMID- 26678331 TI - Implications from Under-reporting at Lifetime, Death Certificate Notifications and Trace-back on the Recorded Incidence of a "Newly" Established Population based Cancer Registry. AB - OBJECTIVES: Population-based cancer registries (CRs) are powerful tools for measuring cancer burden and progress against cancer. The study's objective was to investigate the effects of under-reporting at lifetime, death certificate notifications, and trace-back on the incidence a newly established population based CR may record during its initial 15 years of operation. METHODS: Using cancer data of nine CRs of the SEER programme we performed model calculations to investigate temporal trends of the recorded incidence that might be expected if registration started in 1995 with gradually increasing proportions of cancers reported to the CR. It was assumed that the CR obtains all death certificates providing cancer as the underlying cause of death. Different scenarios with regard to the development of the proportions of cancers reported to the CR and the use of trace-back were evaluated. RESULTS: Our model calculations demonstrated that the inclusion of cancers notified from death certificates which were diagnosed prior to the start of registration and which attribute to the incidence estimates of the year of death ('prevalent' cases) may compensate under reporting typically observed right after the start of a CR. The recorded incidence may even be overestimated during the first years of registration, if large amounts of prevalent cancers are notified from death certificates (e.g. overestimation of lung cancer incidence by 8% and 21% in the first year of registration, if the proportions of cases reported were 50% and 70% in that year, overestimation of myeloma incidence still exceeding 5% after eight years of registration, if the proportion of cases reported to the CR had reached 97.5% after six years). Trace-back may effectively reduce the recorded surplus cancer cases. CONCLUSIONS: During the initial years of registration, the inclusion of prevalent cancers from death certificates may compensate the higher amount of underreporting right after the start of a CR. Accurate incidence estimates may nevertheless be observed for highly fatal cancers if substantial proportions of cancer cases are missed at lifetime, however apparent incidence trends observed in the initial years of registration need to be interpreted with caution. PMID- 26678332 TI - Glioma Stem-like Cells Keep Their H3.3 Variant Levels at Bay. AB - Pediatric glioblastomas (GBMs) commonly harbor mutations in histone variant H3.3, while adult GBMs do not. In this issue of Cancer Cell, Gallo and colleagues demonstrate that adult GBM stem-like cells repress H3.3 expression to maintain self-renewal properties. PMID- 26678333 TI - Take It Down a NOTCH in Forebrain Tumors. AB - In this issue of Cancer Cell, Giachino and colleagues, employing various approaches, describe a tumor suppressor function for Notch signaling in forebrain tumors and suggest that decreased Notch activity could be a key molecular event in supratentorial primitive neuroectodermal tumors (sPNET). PMID- 26678334 TI - Stemming Colorectal Cancer Growth and Metastasis: HOXA5 Forces Cancer Stem Cells to Differentiate. AB - Wnt signaling drives colorectal cancer stem cells, but effective therapeutics targeting these cells and their signaling pathways are lacking. In this issue of Cancer Cell, Ordonez-Moran and colleagues describe a promising therapeutic intervention for colorectal cancers that selectively induces cancer stem cell differentiation through HOXA5 expression and Wnt signaling inhibition. PMID- 26678335 TI - Getting Tumor Dendritic Cells to Engage the Dead. AB - The immunogenic effects of chemotherapy rely on effective activation of dendritic cells to present antigen to tumor-specific T cells. However, the signals that govern how dendritic cells seek out dying cancer cells to initiate this process are poorly understood. A recent study by Vacchelli et al. provides important insight. PMID- 26678336 TI - Immunotherapy Not Working? Check Your Microbiota. AB - Gut microbes have ascended to prominence as key modulators of host immunity, raising the possibility that they could influence the outcome of cancer immunotherapy. Two recent studies address this question by identifying specific gut-resident bacteria as drivers of checkpoint blockade immunotherapy in pre clinical tumor models. PMID- 26678337 TI - Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. AB - The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy. Although largely neglected in the clinical practice, accumulating evidence indicates that the efficacy of conventional and targeted anticancer agents does not only involve direct cytostatic/cytotoxic effects, but also relies on the (re)activation of tumor-targeting immune responses. Chemotherapy can promote such responses by increasing the immunogenicity of malignant cells, or by inhibiting immunosuppressive circuitries that are established by developing neoplasms. These immunological "side" effects of chemotherapy are desirable, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy. PMID- 26678338 TI - A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in Mammary Epithelial Cells and Breast Cancer. AB - In several developmental lineages, an increase in MYC expression drives the transition from quiescent stem cells to transit-amplifying cells. We show that MYC activates a stereotypic transcriptional program of genes involved in cell growth in mammary epithelial cells. This change in gene expression indirectly inhibits the YAP/TAZ co-activators, which maintain the clonogenic potential of these cells. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. MYC-dependent growth strains cellular energy resources and stimulates AMP-activated kinase (AMPK). PLD6 alters mitochondrial fusion and fission dynamics downstream of MYC. This change activates AMPK, which in turn inhibits YAP/TAZ. Mouse models and human pathological data show that MYC enhances AMPK and suppresses YAP/TAZ activity in mammary tumors. PMID- 26678339 TI - Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion. AB - Heterozygous mutation of IDH1 in cancers modifies IDH1 enzymatic activity, reprogramming metabolite flux and markedly elevating 2-hydroxyglutarate (2-HG). Here, we found that 2-HG depletion did not inhibit growth of several IDH1 mutant solid cancer types. To identify other metabolic therapeutic targets, we systematically profiled metabolites in endogenous IDH1 mutant cancer cells after mutant IDH1 inhibition and discovered a profound vulnerability to depletion of the coenzyme NAD+. Mutant IDH1 lowered NAD+ levels by downregulating the NAD+ salvage pathway enzyme nicotinate phosphoribosyltransferase (Naprt1), sensitizing to NAD+ depletion via concomitant nicotinamide phosphoribosyltransferase (NAMPT) inhibition. NAD+ depletion activated the intracellular energy sensor AMPK, triggered autophagy, and resulted in cytotoxicity. Thus, we identify NAD+ depletion as a metabolic susceptibility of IDH1 mutant cancers. PMID- 26678341 TI - HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer. AB - Hierarchical organization of tissues relies on stem cells, which either self renew or produce committed progenitors predestined for lineage differentiation. Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is downregulated, and its re-expression induces loss of the cancer stem cell phenotype, preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represent tangible means to treat colon cancer by eliminating cancer stem cells. PMID- 26678340 TI - Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells. AB - Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the basement membrane, PMNs impeded early-stage tumor growth and retarded malignant progression. Unexpectedly, PMN recruitment and tumor growth control occurred independently of lymphocytes and cellular senescence and instead ensued as part of the tumor's intrinsic inflammatory response to hypoxia. In humans, a PMN gene signature correlated with improved survival in several cancer subtypes, including PTEN-deficient uterine cancer. These findings provide insight into tumor associated PMNs and reveal a context-specific capacity for PMNs to directly combat tumorigenesis. PMID- 26678343 TI - Metabolism of the carcinogen alpha-asarone in liver microsomes. AB - Alpha-asarone (1) is a naturally occurring phenylpropene found in several plants, e.g. Acorus calamus. 1-containing plant materials and essential oils thereof are used for flavoring foods and in many phytopharmaceuticals. 1 has been claimed to have positive pharmacological effects, however, it is carcinogenic in male mice (liver) and probably genotoxic. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rat, bovine, porcine, and human origin using HPLC-DAD and LC-ESI-MS/MS and derived kinetic data on the metabolite formation. The main metabolic pathway was the side-chain hydroxylation leading to (E)-3'-hydroxyasarone (2). Epoxidation of 1 presumably led to (E)-asarone-1',2' epoxide (4) which instantly hydrolyzed to form erythro- and threo-configured diols (5b+5a). As a minor reaction O-demethylation of 1 was observed. The metabolite formation showed little species-specific differences with the exception of porcine liver microsomes for which the formation of diols 5b+5a exceeded the formation of alcohol 2. The kinetic parameters imply a dependence of the pattern of metabolite formation from substrate concentration. On the basis of our results and earlier findings we hypothesize the genotoxic epoxide 4 being the ultimate carcinogen metabolically formed from 1. PMID- 26678342 TI - Adverse prognosis and distinct progression patterns after concurrent chemoradiotherapy for glioblastoma with synchronous subventricular zone and corpus callosum invasion. AB - BACKGROUND AND PURPOSE: The subventricular zone (SVZ) and the corpus callosum (CC) invasion status are separately associated with adverse prognosis for glioblastoma. We investigated the prognosis and progression patterns of glioblastoma with and without synchronous SVZ and CC (sSVZCC) invasion. MATERIAL AND METHODS: Glioblastoma patients completing concurrent chemoradiotherapy with temozolomide were retrospectively categorized by the preoperative sSVZCC invasion status. The associations between sSVZCC invasion and the survival and progression patterns were analyzed. RESULTS: In total, 108 patients, including 36 with sSVZCC invasion, were followed for a median period of 60.2 (range 34.2-86.3) months. The median overall survival (OS) of patients with and without sSVZCC were 18.6 and 26.4 months, respectively (p=0.005). Using multivariate analyses with the factors of age, performance, surgery extent, and tumor size, sSVZCC invasion remained significant for a poor OS (hazard ratio, 1.96; 95% confidence interval, 1.19 3.21). The rates of progression at tumor bed, preoperative edematous areas, bilateral hemispheres, and ventricles for tumors with and without sSVZCC invasion were 75% and 63.9% (p=0.282), 41.7% and 9.7% (p<0.001), 47.2% and 13.9% (p<0.001), and 38.9% and 13.9% (p=0.006), respectively. CONCLUSIONS: The sSVZCC invasion status determined the distinct prognosis and progression areas of glioblastoma, which suggests individualized radiotherapy and drug administration strategies. PMID- 26678344 TI - Absolute measurement of (198)Au activity in gold foil using plastic scintillators and a well-type NaI(Tl) detector. AB - A beta-gamma coincidence system has been developed for measuring (198)Au activity in gold foils. The system was validated by Monte Carlo simulations and by measuring the activity of a (60)Co point-source. To study effects such as self shielding of beta particles in gold foils, (198)Au activity measurements and simulations were performed for various scintillators and foil sizes. The measured (198)Au activities were ~1% above the reference activity, which might be due to self-shielding of beta particles. The measured and simulated (198)Au activities agreed, suggesting feasibility of precise activity measurement. PMID- 26678345 TI - Unusual echocardiographic appearance of a cardiac metastasis from lung carcinoma. AB - During hospitalization in the Oncology Department, a woman with nonsmall cell lung cancer and no previous cardiac event complained of episodes of chest pain and palpitations. Preliminary instrumental examinations diagnosed atrial fibrillation in pericarditis. A subsequent complete transthoracic echocardiogram showed the presence of a large mass involving the left ventricular apex, without echo-contrast enhancement. A thoracic CT with iodized contrast agent revealed its necrotic composition and was concluded as cardiac metastasis. This is an unusual case of a malignant neoplasm showing no contrast enhancement at echocardiogram because of its necrotic composition, mimicking a thrombus. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:392-394, 2016. PMID- 26678346 TI - Covalently Attached Porphycene-Ferrocene Dyads: Synthesis, Redox-Switched Emission, and Observation of the Charge-Separated State. AB - Two new porphycenes functionalized with ferrocenyl pendants have been synthesized and characterized spectroscopically and structurally. The porphycene-based emission in porphycene-ferrocene dyads was switched on and off by the reversible control of the ferrocenyl pendant redox states. Transient absorption spectroscopy with a femtosecond laser-pulsed technique has successfully detected the picosecond charge-separated excited state of the dyad upon Q-band excitation of the porphycene ring. PMID- 26678347 TI - Old lines tell new tales: Blaschko linear lupus erythematosis. AB - Patients with lupus erythematosus (LE) specific cutaneous manifestations distributed along the lines of Blaschko are seldom encountered in clinic. In this paper, we reported 5 new cases and perform a systematic review of all the published cases in the English and Chinese literature. We provide a comprehensive summary of the clinical manifestations and explore potential etiology and pathogenesis. Sixty-eight published papers (53 English and 15 Chinese) and 93 cases (including 5 cases reported by us) were included in the analysis. In contrast to classical cutaneous LE, these cases have a series of distinctive clinical features and also have a potentially unique pathogenesis. The pathogenesis of this condition may involve the presence of mosaic abnormal skin cells, possessing crucial pathogenic gene(s)/epigenetic modification(s), located along the lines of Blaschko during embryogenesis. A comparison of the mosaic cells and surrounding "wild-type" cells and in-depth exploration of the interaction between susceptive gene(s)/epigenetic modification(s) and the immune system may potentially bring to light the secrets hidden in LE. Thus, we consider this condition to be a distinct subtype of LE and "Blaschko-linear lupus erythematosus" would be a more appropriate designation. The clues provided in the study of the pathogenesis of this form of LE may potentially unlock the mysteries of the various forms of LE as a whole. PMID- 26678348 TI - Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET. AB - Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder with a strong genetic component. The norepinephrine transporter (NET) is a key target for ADHD treatment and the NET gene has been of high interest as a possible modulator of ADHD pathophysiology. Therefore, we conducted an imaging genetics study to examine possible effects of single nucleotide polymorphisms (SNPs) within the NET gene on NET nondisplaceable binding potential (BPND ) in patients with ADHD and healthy controls (HCs). Twenty adult patients with ADHD and 20 HCs underwent (S,S)-[18F]FMeNER-D2 positron emission tomography (PET) and were genotyped on a MassARRAY MALDI-TOF platform using the Sequenom iPLEX assay. Linear mixed models analyses revealed a genotype-dependent difference in NET BPND between groups in the thalamus and cerebellum. In the thalamus, a functional promoter SNP (-3081 A/T) and a 5'-untranslated region (5'UTR) SNP (-182 T/C), showed higher binding in ADHD patients compared to HCs depending on the major allele. Furthermore, we detected an effect of genotype in HCs, with major allele carriers having lower binding. In contrast, for two 3'UTR SNPs (*269 T/C, *417 A/T), ADHD subjects had lower binding in the cerebellum compared to HCs depending on the major allele. Additionally, symptoms of hyperactivity and impulsivity correlated with NET BPND in the cerebellum depending on genotype. Symptoms correlated positively with cerebellar NET BPND for the major allele, while symptoms correlated negatively to NET BPND in minor allele carriers. Our findings support the role of genetic influence of the NE system on NET binding to be pertubated in ADHD. PMID- 26678349 TI - Postoperative complications and overall survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. AB - INTRODUCTION: Pancreaticoduodenectomy (PD) performed for pancreatic ductal adenocarcinoma (PDA) has a postoperative morbidity of 40-50%. In this study, we analyzed the impact of high grade complications after PD for PDA on overall survival. METHODS: A total of 596 patients that underwent PD for PDA between 2001 and 2009 were identified from a prospective database. Complications were defined and graded (1-5) as per our Institutional Surgical Secondary Events Program. High grade complications were defined as >=grade 3. Postoperative mortality (<=90 days) was excluded. Univariate and multivariate analyses were performed to identify factors associated with overall survival. RESULTS: Median survival was 24 months. Overall complication rate was 51% (301/596). Low grade complications were recorded in 266 patients (45%) and high grade complications in 22% (n = 129). Our 90 day mortality was 3.7% (n = 22). Anastomotic fistula/leak/abscess rate was 14% (n = 82). Multivariate Cox-Regression analysis identified node positivity, estimated blood loss (EBL) >600 ml, length of stay (LOS) >10 days, margin positivity, and vascular procedures as predictors of decreased overall survival (P < 0.05). High grade complications were not associated with overall survival (P = 0.948). CONCLUSION: In this study, the occurrence of high grade postoperative complications was not associated with overall survival. PMID- 26678350 TI - Comparison of Chromosome 4 gene expression profile between lung telocytes and other local cell types. AB - Telocytes (TCs) are new cellular entities of mesenchymal origin described almost ubiquitously in human and mammalian organs (www.telocytes.com). Different subtypes of TCs were described, all forming networks in the interstitial space by homo- and heterocellular junctions. Previous studies analysed the gene expression profiles of chromosomes 1, 2, 3, 17 and 18 of murine pulmonary TCs. In this study, we analysed by bioinformatics tools the gene expression profiles of chromosome 4 for murine pulmonary TCs and compared it with mesenchymal stem cells (MSCs), fibroblasts (Fbs), alveolar type II cells (ATII), airway basal cells, proximal airway cells, CD8(+) T cells from bronchial lymph nodes (T-BL) and CD8(+) T cells from lungs (T-L). Key functional genes were identified with the aid of the reference library of the National Center for Biotechnology Information Gene Expression Omnibus database. Seventeen genes were up-regulated and 56 genes were down-regulated in chromosome 4 of TCs compared with other cells. Four genes (Akap2, Gpr153, Sdc3 and Tbc1d2) were up-regulated between one and fourfold and one gene, Svep1, was overexpressed over fourfold. The main functional networks were identified and analysed, pointing out to a TCs involvement in cellular signalling, regulation of tissue inflammation and cell expansion and movement. PMID- 26678351 TI - Olfactory-specific quality of life outcomes after endoscopic sinus surgery. AB - BACKGROUND: Olfactory loss is a cardinal symptom of chronic rhinosinusitis (CRS) and affects 40% to 80% of patients. However, common sinus-specific quality-of life (QOL) instruments include only single questions related to olfaction. Few studies have explored olfactory outcomes after surgery utilizing validated, olfaction-specific QOL questionnaires. METHODS: Patients with CRS were enrolled from 3 centers across North America into a prospective cohort study. Patients completed the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS) and the 40-item Smell Identification Test (SIT-40) before and at least 6 months after endoscopic sinus surgery (ESS). Multivariate linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with QOD scores at baseline or predicted change after surgery. RESULTS: A total of 121 patients, equally split between genders, were enrolled with an average age of 47.9 years (range, 18-80 years). Baseline total QOD-NS scores were significantly associated with SIT-40 scores, with a moderate strength of correlation (Rs = 0.400; p < 0.001). The average QOD NS score improved after ESS (35.7 +/- 13.0 vs 39.7 +/- 12.2; p = 0.006). Allergy, polyps, and steroid-dependent conditions were found to be independently associated with worse preoperative QOD-NS scores, whereas septal deviation was associated with better QOD-NS scores. Baseline computed tomography (CT) scores were the only variable that significantly predicted change in QOD-NS after surgery. CONCLUSION: Olfaction-specific QOL is worse in patients with polyps and comorbid allergy. Significant improvements in olfaction-specific QOL are seen after ESS, with the greatest gains seen in those with worse CT scores at baseline. PMID- 26678352 TI - Decomposing genomic variance using information from GWA, GWE and eQTL analysis. AB - A commonly used procedure in genome-wide association (GWA), genome-wide expression (GWE) and expression quantitative trait locus (eQTL) analyses is based on a bottom-up experimental approach that attempts to individually associate molecular variants with complex traits. Top-down modeling of the entire set of genomic data and partitioning of the overall variance into subcomponents may provide further insight into the genetic basis of complex traits. To test this approach, we performed a whole-genome variance components analysis and partitioned the genomic variance using information from GWA, GWE and eQTL analyses of growth-related traits in a mouse F2 population. We characterized the mouse trait genetic architecture by ordering single nucleotide polymorphisms (SNPs) based on their P-values and studying the areas under the curve (AUCs). The observed traits were found to have a genomic variance profile that differed significantly from that expected of a trait under an infinitesimal model. This situation was particularly true for both body weight and body fat, for which the AUCs were much higher compared with that of glucose. In addition, SNPs with a high degree of trait-specific regulatory potential (SNPs associated with subset of transcripts that significantly associated with a specific trait) explained a larger proportion of the genomic variance than did SNPs with high overall regulatory potential (SNPs associated with transcripts using traditional eQTL analysis). We introduced AUC measures of genomic variance profiles that can be used to quantify relative importance of SNPs as well as degree of deviation of a trait's inheritance from an infinitesimal model. The shape of the curve aids global understanding of traits: The steeper the left-hand side of the curve, the fewer the number of SNPs controlling most of the phenotypic variance. PMID- 26678353 TI - Towards exposure limits for working postures and musculoskeletal symptoms - a prospective cohort study. AB - Occupational postures are considered to be an important group of risk factors for musculoskeletal pain. However, the exposure-outcome association is not clear yet. Therefore, we aimed to determine the exposure-outcome association of working postures and musculoskeletal symptoms. Also, we aimed to establish exposure limits for working postures. In a prospective cohort study among 789 workers, intensity, frequency and duration of postures were assessed at baseline using observations. Musculoskeletal pain was assessed cross-sectionally and longitudinally and associations of postures and pain were addressed using logistic regression analyses. Cut-off points were estimated based on ROC-curve analyses. Associations were found for kneeling/crouching and low-back pain, neck flexion and rotation and neck pain, trunk flexion and low-back pain, and arm elevation and neck and shoulder pain. The results provide insight into exposure outcome relations between working postures and musculoskeletal symptoms as well as evidence-based working posture exposure limits that can be used in future guidelines and risk assessment tools. Practitioner Summary: Our study gives insight into exposure-outcome associations of working postures and musculoskeletal symptoms (kneeling/crouching and low-back pain, neck flexion/rotation and neck pain, trunk flexion and low-back pain, and arm elevation and neck and shoulder pain). Results furthermore deliver evidence-based postural exposure limits that can be used in guidelines and risk assessments. PMID- 26678354 TI - Computed tomographic study of anatomical relationship between pubic symphysis and ischial spines to improve interpretation of intrapartum translabial ultrasound. AB - OBJECTIVE: To analyze the anatomical relationship between the pubic symphysis and the ischial spines to determine reliable landmarks for the assessment of fetal head descent by intrapartum translabial ultrasound (ITU). METHODS: All computed tomography (CT) scans performed for breech presentation and for twin delivery between 2006 and 2014 in a tertiary university hospital were obtained for measurement and analysis by two operators. The symphysis-left ischial spine angle (SIA) and the symphysis-left ischial spine distance (SID) were measured on three dimensional reconstructions from the CT volume dataset. We calculated intra- and interobserver agreements for SIA and SID with 95% prediction intervals, created Bland-Altman plots with 95% limits of agreement and estimated the intraclass correlation coefficient (ICC). A sagittal plane projection from the SIA enabled calculation of a sagittal angle, corresponding to the angle of progression (AoP) on ITU. RESULTS: SIA and SID were obtained from CT images from 458 women. Reproducibility was good for both SIA (intraobserver ICC, 0.94 (95% CI, 0.88 0.97) and interobserver ICC, 0.81 (95% CI, 0.66-0.92)) and SID (intraobserver ICC, 0.92 (95% CI, 0.82-0.97) and interobserver ICC, 0.83 (95% CI, 0.73-0.92)). The median SIA was 106 degrees (interquartile range (IQR), 105-109 degrees ) and median SID was 26.1 (IQR, 23.4-29.5) mm. SIA and SID were not correlated with pelvic diameter or height. The 50th percentile of AoP was 110 degrees . CONCLUSION: Knowledge of the anatomical relationship between the pubic symphysis and ischial spines makes it possible to establish a sonographic method for assesssing fetal head descent by taking into account the level of the ischial spines. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26678355 TI - Receiver operating characteristic analysis under tree orderings of disease classes. AB - Receiver operating characteristic (ROC) curve and its summary statistics (e.g., the area under curve (AUC)) are commonly used to evaluate the diagnostic accuracy for disease processes with binary classification. The ROC curve has been extended to ROC surface for scenarios with three ordinal classes or to hyper-surface for scenarios with more than three classes. For classifier under tree or umbrella ordering in which the marker measurement for one class is lower or higher than those for the other classes, the commonly adopted diagnostic measures are the naive AUC (NAUC) based on a pooled class of all the unordered classes and the umbrella volume (UV) based on the concept of volume under surface. However, both NAUC and UV have some limitations. For example, NAUC depends on the sampling weights for all the classes in population, and UV has only been introduced for three-class settings. In this article, we initiate the idea of a new ROC framework for tree or umbrella ordering (denoted as TROC) and propose the area under TROC curve (denoted as TAUC) as an appropriate diagnostic measure. The proposed TROC and TAUC share many nice features with the traditional ROC and AUC. Both parametric and nonparametric approaches are explored to construct the confidence interval estimation of TAUC. The performances of these methods are compared in simulation studies under a variety settings. At the end, the proposed methods are applied to a published microarray data set. PMID- 26678356 TI - Myeloid cell-derived LRG attenuates adverse cardiac remodelling after myocardial infarction. AB - AIMS: Leucine-rich alpha2-glycoprotein (LRG) is considered as a biomarker of the clinical activities of chronic inflammatory diseases, including heart failure. However, its pathophysiological roles in cardiac remodelling after myocardial infarction (MI) remain to be clarified. In this study, we have addressed functional roles of LRG in cardiac remodelling after MI. METHODS AND RESULTS: MI was generated by ligating the left coronary artery in mice. Real-time reverse transcription (RT)-PCR and immunoblot analyses revealed that the expressions of LRG transcript and protein were up-regulated in post-infarct myocardium. LRG protein was produced by heart-infiltrating myeloid cells, such as macrophages and neutrophils. To elucidate functional roles of LRG in cardiac remodelling, we generated MI in wild-type (WT) and LRG-deficient (LRG(-/-)) mice and found that LRG gene ablation aggravated myocardial fibrosis with cardiac dysfunction after MI. Immunohistochemical analyses with anti-CD31 antibody revealed that capillary density decreased at border zone in LRG(-/-) mice compared with WT mice. Consistently, the expression of apelin receptor was reduced in LRG(-/-) mice, implying that the impaired angiogenic activity is associated with adverse cardiac remodelling in LRG(-/-) mice. Moreover, LRG gene ablation suppressed the activation of smad1/5/8, a pro-angiogenic signalling pathway. Finally, the transplantation of WT bone marrow cells into LRG(-/-) mice attenuated cardiac fibrosis with functional improvement after MI, accompanied by restoration of capillary density compared with the bone marrow transplantation from LRG(-/-) mice. CONCLUSION: LRG, produced by heart-infiltrating myeloid cells, suppresses adverse cardiac remodelling after MI as a novel cardioprotective factor. LRG signalling could be a therapeutic target against cardiovascular diseases. PMID- 26678357 TI - Combination nanotherapy penetrates atherosclerosis. PMID- 26678358 TI - Tonsillectomy and the risk of inflammatory bowel disease: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: Tonsillectomy remains a controversial environmental factor in the etiology of inflammatory bowel disease (IBD). This meta-analysis aims to elucidate a more defined role of tonsillectomy in the development of IBD. METHODS: Four databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science, were searched for studies exploring the association between tonsillectomy and the risk of IBD. The pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was assessed using chi-squared and I(2) statistical analysis. A funnel plot was performed to assess publication bias. RESULTS: A total of 23 observational studies involving 19 569 patients were included in our meta analysis. Of these, 17 studies investigated the association between tonsillectomy and Crohn's disease (CD), and 22 studies explored its relationship with ulcerative colitis (UC). Overall, a positive relationship between tonsillectomy and development of CD (OR 1.37, 95% CI: 1.16-1.62) was observed, while there was no association between tonsillectomy and UC (OR 0.94, 95% CI: 0.84-1.05). When ORs were adjusted for smoking, the pooled OR for CD increased to 1.66 (95% CI: 1.03-2.68) and, for UC, changed to 1.03 (95% CI: 0.74-1.44). CONCLUSIONS: This meta-analysis demonstrates that tonsillectomy is associated with an increased risk of developing CD. We found no evidence to suggest that tonsillectomy exerts a protective effect on the development of UC, as is the case with appendectomy. Further prospective studies are required to confirm the validity of these observations. PMID- 26678359 TI - An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI. AB - Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy. PMID- 26678361 TI - Image quality and effective dose of a robotic flat panel 3D C-arm vs computed tomography. AB - BACKGROUND: The aim of this study was to determine the effective dose and corresponding image quality of different imaging protocols of a robotic 3D flat panel C-arm in comparison to computed tomography (CT). METHODS: Dose measurements were performed using a Rando-Alderson Phantom. The phantom was exposed to different scanning protocols of the 3D C-arm and the CT. Pedicle screws were inserted in a fresh swine cadaver. Images were obtained using the same scanning protocols. RESULTS: At the thoracolumbar junction, the effective dose was comparable for 3D high-dose protocols, with (4.4 mSv) and without (4.3 mSv) collimation and routine CT (5 mSv), as well as a dose-reduction CT (4.0 mSv). A relevant reduction was achieved with the 3D low-dose protocol (1.0 mSv). Focusing on Th6, a similar reduction with the 3D low-dose protocol was achieved. The image quality of the 3D protocols using titanium screws was rated as 'good' by all viewers, with excellent correlation. CONCLUSIONS: Modern intra-operative 3D-C arms produce images of CT-like quality with low-dose radiation. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26678360 TI - Frequency of "Time for Self" Is a Significant Predictor of Postnatal Depressive Symptoms: Results from a Prospective Pregnancy Cohort Study. AB - BACKGROUND: We aimed to explore the relationship between frequency of time for self and maternal depressive symptoms at 6 months postpartum. METHODS: A prospective cohort study of 1,507 first-time mothers in Australia, recruited in early pregnancy with follow-up at 6 months postpartum, was conducted. Scores of more than or equal to 13 on the Edinburgh Postnatal Depression Scale were used to identify depressive symptoms. RESULTS: Of 1,507 women recruited to the study, 92.6 percent completed follow-up at 6 months postpartum. Almost half (48.5%) reported having time for themselves when someone else looked after their baby (time for self) once a week or more. Compared with women who reported less frequent time for self, women who had time for themselves once a week or more were less likely to report depressive symptoms (unadjusted OR 0.44 [95% CI 0.30 0.66]). Women who had more frequent time for themselves were more likely to have more practical and emotional support. However, this only partially explained the relationship between time for self and depressive symptoms, which remained significant in regression models after adjusting for other recognized risk factors for maternal depression, including social support (adjusted OR 0.60 [95% CI 0.39-0.94]). CONCLUSIONS: Our findings suggest that having time for self at least once a week in the first 6 months after childbirth may have a beneficial influence on maternal mental health. Ensuring women get regular respite from the challenges of caring for a young baby may be a relatively simple and effective way of promoting maternal mental health in the year after childbirth. PMID- 26678362 TI - Diagnosis and clinical presentation of hemoglobin Kirksey. AB - More than 1000 hemoglobin (Hb) variants have been identified. Hb Kirksey, a rare Hb variant involving mutation at codon 94 of alpha2-globin, is associated with low oxygen affinity. To our knowledge, there is no case report on Hb Kirksey in the literature, and, accordingly, the clinical features of patients with Hb Kirksey are currently unknown. We report here the case of a neonate who presented with asymptomatic low oxygen saturation on pulse oximetry (SpO2 ) just after birth, together with clinical analysis of the sister and cousin. Based on the presentations, Hb Kirksey does not seem to be associated with clinical abnormalities. Discrepancy between SpO2 and partial pressure of arterial oxygen (PaO2 ) detected on arterial blood gas analysis provided a clue to the diagnosis. Hb variants should be suspected and arterial blood gases should be measured in pediatric cases of unexplained low SpO2 . PMID- 26678363 TI - Systematic Literature Review of Risk Factors and Treatments for Ulcerative Dermatitis in C57BL/6 Mice. AB - Ulcerative dermatitis (UD) in C57BL/6 mice is poorly understood and challenging to treat. We sought to evaluate the evidence regarding commonly cited risk factors for UD and reported UD treatments. The terms 'ulcerative dermatitis' and 'C57BL/6' were used to search 3 electronic databases. The resulting 347 articles were screened to identify publications that compared the risk of spontaneous UD in wild-type C57BL/6 mice according to sex, season, diet, or age and those that compared the degree of healing or rate of lesion resolution according to the intervention used. Articles were evaluated by using published criteria for assessing methodologic quality, including study design, number of animals per study group, case definition, method of diagnosis, randomization, enrollment criteria, exclusion criteria, and outcomes. The search identified 11 publications on risk factors that met the inclusion criteria, and no publication on UD treatment met all of the criteria. Relaxing the inclusion criteria for reporting of risk factors and treatment outcomes to include both wild-type C57BL/6 mice and genetically engineered mice on a B6 background yielded 12 publications on risk factors and 3 publications on treatment. Dietary factors, particularly caloric restriction, appear to influence UD risk. Female sex was inconsistently associated with a higher risk of UD, which most often occurred in 13- to 24-mo old mice in the studies that were reviewed. Only 1 of the 3 publications that evaluated UD treatments included an untreated group or alternative therapy control. Further research is needed to explore epidemiologic aspects of UD and to compare treatment options. PMID- 26678364 TI - Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth. AB - Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities. PMID- 26678365 TI - Struvite Urolithiasis in Long-Evans Rats. AB - Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well. PMID- 26678366 TI - Assessment of Blood Collection from the Lateral Saphenous Vein for Microfilaria Counts in Mongolian Gerbils (Meriones unguiculatus) Infected with Brugia pahangi. AB - The NIH guidelines for survival bleeding of mice and rats note that using the retroorbital plexus has a greater potential for complications than do other methods of blood collection and that this procedure should be performed on anesthetized animals. Lateral saphenous vein puncture has a low potential for complications and can be performed without anesthesia. Mongolian gerbils (Meriones unguiculatus) are the preferred rodent model for filarial parasite research. To monitor microfilaria counts in the blood, blood sampling from the orbital plexus has been the standard. Our goal was to refine the blood collection technique. To determine whether blood collection from the lateral saphenous vein was a feasible alternative to retroorbital sampling, we compared microfilaria counts in blood samples collected by both methods from 21 gerbils infected with the filarial parasitic worm Brugia pahangi. Lateral saphenous vein counts were equivalent to retroorbital counts at relatively high counts (greater than 50 microfilariae per 20 MUL) but were significantly lower than retroorbital counts when microfilarial concentrations were lower. Our results indicate that although retroorbital collection may be preferable when low concentrations of microfilariae need to be enumerated, the lateral saphenous vein is a suitable alternative site for blood sampling to determine microfilaremia and is a feasible refinement that can benefit the wellbeing of gerbils. PMID- 26678368 TI - Systemic Coronaviral Disease in 5 Ferrets. AB - The prevalence of reported systemic coronaviral disease in ferrets (Mustela putorius furo), which resembles the dry form of feline infectious peritonitis, has been increasing in the literature since its initial diagnosis and characterization approximately 10 y ago. Here we describe the clinical signs, pathologic findings, and diagnosis by immunohistochemistry using an FIPV3-70 monoclonal antibody of systemic coronaviral disease in 5 ferrets, 2 of which were strictly laboratory-housed; the remaining 3 were referred from veterinary private practices. This case report illustrates the importance of considering FRSCV infection as a differential diagnosis in young, debilitated ferrets with abdominal masses and other supporting clinical signs. PMID- 26678367 TI - Rabbit Models for Studying Human Infectious Diseases. AB - Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID- 26678371 TI - Mural Dissections of Brain-Supplying Arteries in a Chimpanzee (Pan troglodytes). AB - We describe the pathologic features of mural arterial dissection involving brain supplying arteries in a 31-y-old female chimpanzee (Pan troglodytes). Several hours after examination for a possible respiratory tract infection, the chimpanzee became unresponsive, developed seizures, and died within 18 h. At necropsy, the occipital cortex of the brain had a small area of congestion, and the cerebellar cortex contained a small necrotic area. Histologic evaluation confirmed the cortical lesions and revealed an additional necrotic area in the medulla oblongata characterized by mural dissection of the brain-supplying vertebral and basilar arteries and subsequent branches. Lesions in the cortices and medulla were within areas supplied by the vertebrobasilar system. Dissection of brain-supplying arteries has been described in humans but not previously in chimpanzees (or any other NHP), suggesting that these species might be useful in understanding this condition in humans. In addition, the lesion should be added to the NHP clinician's and pathologist's differential diagnosis list for similar presentations in this species. PMID- 26678370 TI - Multispecies Epidemiologic Surveillance Study after an Outbreak of Yersiniosis at an African Green Monkey Research Facility. AB - After an outbreak of Yersinia enterocolitica at a NHP research facility, we performed a multispecies investigation of the prevalence of Yersinia spp. in various mammals that resided or foraged on the grounds of the facility, to better understand the epizootiology of yersiniosis. Blood samples and fecal and rectal swabs were obtained from 105 captive African green monkeys (AGM), 12 feral cats, 2 dogs, 20 mice, 12 rats, and 3 mongooses. Total DNA extracted from swab suspensions served as template for the detection of Y. enterocolitica DNA by real time PCR. Neither Y. enterocolitica organisms nor their DNA were detected from any of these samples. However, Western blotting revealed the presence of Yersinia antibodies in plasma. The AGM samples revealed a seroprevalence of 91% for Yersinia spp. and of 61% for Y. enterocolitica specifically. The AGM that were housed in cages where at least one fatality occurred during the outbreak (clinical group) had similar seroprevalence to that of AGM housed in unaffected cages (nonclinical group). However, the nonclinical group was older than the clinical group. In addition, 25%, 100%, 33%, 10%, and 10% of the sampled local cats, dogs, mongooses, rats, and mice, respectively, were seropositive. The high seroprevalence after this outbreak suggests that Y. enterocolitica was transmitted effectively through the captive AGM population and that age was an important risk factor for disease. Knowledge regarding local environmental sources of Y. enterocolitica and the possible role of wildlife in the maintenance of yersiniosis is necessary to prevent and manage this disease. PMID- 26678369 TI - Temporal Evolution of MRI Characteristics in Dogs with Collagenase-Induced Intracerebral Hemorrhage. AB - Intracerebral hemorrhage (ICH) is one of the most lethal types of stroke. Neuroimaging techniques, particularly MRI, have improved the diagnostic accuracy of ICH. The MRI characteristics of the evolving stages of ICH in humans-but not those in dogs-have been described. In this study, we document the temporal MRI characteristics in a canine model of collagenase-induced ICH. Specifically, ICH was induced in 5 healthy beagles by injecting 500 U of bacterial collagenase from Clostridium histolyticum, which was delivered into the parietal lobe over 5 min by using a microinfusion pump. T1- and T2-weighted, fluid-attenuated inversion recovery, gradient-echo (GRE), and diffusion-weighted (DWI) imaging and measurement of the apparent diffusion coefficient (ADC) were performed serially at 6 different time points (before and 12 h, 3 d, 5 d, 10 d and 24 d after hemorrhage) by using a 3-T MR system. The temporal changes of T1 signal intensity (SI) corresponded well with the reported human data. The temporal changes of T2 and GRE sequences, with the exception of T2 and GRE hyperintensities at the early subacute stage, also matched. ADC measurements were high at the early subacute stage, and DWI-SI positively correlated with T2- and GRE-SI from the early subacute stage onward. In conclusion, MRI is an ideal method for characterizing the temporal evolution of parenchymal alterations after ICH in dogs. These data might be useful for differentiating clinical stages of ICH in dogs. PMID- 26678372 TI - Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis). AB - A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP. PMID- 26678373 TI - Management and outcomes of children with severe burns in New South Wales: 1995 2013. AB - BACKGROUND: As a result of improvements in injury prevention, severe burns appear increasingly uncommon in Australian children. Such injuries continue to have devastating impacts, with major consequences for the patient, their family, treating clinicians and the caring institution. METHODS: A retrospective review was undertaken of Australian children who presented to our institution between 1995 and 2013 with burn injuries >=30% total body surface area (TBSA). RESULTS: Ninety children were identified. Their median age was 3.9 years and 57% (n = 52) were male. Most injuries occurred at home (n = 63) due to fires (n = 49). The majority received inadequate first aid (n = 56) and 40 became hypothermic during initial resuscitation. A total of 79% were transferred from other institutions. The median TBSA burnt was 40% and the majority of burns were full thickness (n = 51). All but nine were managed in the Paediatric Intensive Care Unit with a mean initial hospital admission of 43.5 days. Two thirds of children were intubated, over half of those prior to transfer, with 26 having an inhalational injury and 33 escharotomies. Compared with estimated fluid requirements, most children were over-resuscitated by a median of 26.9 mL/kg. There were seven mortalities. Wound infections were common (n = 65) and 36 suffered sepsis. The median number of dressing changes was 13 (range 0-100), operations were six and packed cells transfused was 95.7 mL/kg. Overall, 54 developed hypertrophic scarring and 45 scar contractures that have required subsequent reconstructive surgery. CONCLUSION: Severe burn injuries in children have significant morbidity and mortality. They would appear expensive to manage and impact substantially on health care resources. PMID- 26678374 TI - Buckling failures in insect exoskeletons. AB - Thin walled tubes are often used for load-bearing structures, in nature and in engineering, because they offer good resistance to bending and torsion at relatively low weight. However, when loaded in bending they are prone to failure by buckling. It is difficult to predict the loading conditions which cause buckling, especially for tubes whose cross sections are not simple shapes. Insights into buckling prevention might be gained by studying this phenomenon in the exoskeletons of insects and other arthropods. We investigated the leg segments (tibiae) of five different insects: the locust (Schistocerca gergaria), American cockroach (Periplaneta americana), death's head cockroach (Blaberus discoidalis), stick insect (Parapachymorpha zomproi) and bumblebee (Bombus terrestris audax). These were tested to failure in cantilever bending and modelled using finite element analysis (FEA). The tibiae of the locust and the cockroaches were found to be approximately circular in shape. Their buckling loads were well predicted by linear elastic FEA, and also by one of the analytical solutions available in the literature for elastic buckling. The legs of the stick insect are also circular in cross section but have several prominent longitudinal ridges. We hypothesised that these ridges might protect the legs against buckling but we found that this was not the case: the loads necessary for elastic buckling were not reached in practice because yield occurred in the material, causing plastic buckling. The legs of bees have a non-circular cross section due to a pollen-carrying feature (the corbicula). We found that this did not significantly affect their resistance to buckling. Our results imply that buckling is the dominant failure mode in the tibia of insects; it likely to be a significant consideration for other arthropods and any organisms with stiff exoskeletons. The interactions displayed here between material properties and cross sectional geometry may provide insights for the biomimetic design of engineering structures using thin walled tubes. PMID- 26678376 TI - Exposure to methyl tert-butyl ether (MTBE) is associated with mitochondrial dysfunction in rat. AB - 1. Methyl tert-butyl ether (MTBE) is commonly used as an octane booster and oxygenate additive to gasoline. The assumed toxic effects of MTBE on human health are a matter of great debate. Exposure to MTBE has been shown to induce oxidative damage and no mechanistic explanation is available so far. Our goals were to determine whether MTBE is a mitochondrial toxicant, if so, what mechanism(s) is involved. 2. Male Sprague-Dawley rats were received MTBE in drinking water for 3 months. At the end of treatments, animals were killed, liver and blood samples were collected for biochemical and histopathological studies, and oxidative stress biomarkers. The rat liver mitochondria were isolated and several mitochondrial indices were measured. 3. We found that zinc plasma levels were remarkably declined with MTBE and N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN; a zinc chelator) exposure. MTBE induced oxidative damage and caused mitochondrial dysfunctions in rats. Supplementation with zinc was able to protect against MTBE-induced cellular and sub-cellular toxicity. 4. Our results demonstrated that long-term exposure to MTBE is associated with zinc deficiency, oxidative stress, and mitochondrial energy failure in rat. PMID- 26678377 TI - Real-time cell analysis and heat shock protein gene expression in the TcA Tribolium castaneum cell line in response to environmental stress conditions. AB - The rust red flour beetle, Tribolium castaneum (Herbst, 1797) (Coleoptera: Tenebrionidae), is a pest of stored grain and one of the most studied insect model species. Some of the previous studies involved heat response studies in terms of survival and heat shock protein expression, which are regulated to protect other proteins against environmental stress conditions. In the present study, we characterize the impedance profile with the xCELLigence Real-Time Cell Analyzer and study the effect of increased temperature in cell growth and viability in the cell line BCIRL-TcA-CLG1 (TcA) of T. castaneum. This novel system measures cells behavior in real time and is applied for the first time to insect cells. Additionally, cells are exposed to heat shock, increased salinity, acidic pH and UV-A light with the aim of measuring the expression levels of Hsp27, Hsp68a, and Hsp83 genes. Results show a high thermotolerance of TcA in terms of cell growth and viability. This result is likely related to gene expression results in which a significant up-regulation of all studied Hsp genes is observed after 1 h of exposure to 40 degrees C and UV light. All 3 genes show similar expression patterns, but Hsp27 seems to be the most affected. The results of this study validate the RTCA method and reveal the utility of insect cell lines, real-time analysis and gene expression studies to better understand the physiological response of insect cells, with potential applications in different fields of biology such as conservation biology and pest management. PMID- 26678375 TI - Marijuana use/cessation expectancies and marijuana use in college students. AB - BACKGROUND: Research suggests that marijuana expectancies are associated with problematic marijuana use; however, these marijuana-related cognitions remain relatively understudied. OBJECTIVE: This study examined marijuana-related decision-making among college students by exploring the relationships among marijuana expectancies and marijuana use variables. METHOD: College students (N = 357) endorsing lifetime marijuana use completed an online survey on marijuana use expectancies, marijuana cessation expectancies, marijuana use, and future marijuana use intentions. A simple regression framework was used to test the effect of each type of expectancies on marijuana outcome; a hierarchical regression framework tested the unique predictive validity when both types were entered into the same model. RESULTS: Both marijuana use expectancies and marijuana cessation expectancies independently predicted a number of marijuana use variables. Additionally, marijuana use expectancies and marijuana cessation expectancies contributed significant unique variance to the prediction of marijuana use. CONCLUSIONS: It is important to consider both use expectancies and cessation expectancies, as these two domains of marijuana-related cognitions appear to act independently, rather than as opposite ends of the same construct. Longitudinal studies are needed to further examine how these factors interact to influence marijuana use and problems over time. PMID- 26678378 TI - Heat Capacity Changes and Disorder-to-Order Transitions in Allosteric Activation. AB - Allosteric coupling in proteins is ubiquitous but incompletely understood, particularly in systems characterized by coupling over large distances. Binding of the allosteric effector, bio-5'-AMP, to the Escherichia coli biotin protein ligase, BirA, enhances the protein's dimerization free energy by -4 kcal/mol. Previous studies revealed that disorder-to-order transitions at the effector binding and dimerization sites, which are separated by 33 A, are integral to functional coupling. Perturbations to the transition at the ligand binding site alter both ligand binding and coupled dimerization. Alanine substitutions in four loops on the dimerization surface yield a range of energetic effects on dimerization. A glycine to alanine substitution at position 142 in one of these loops results in a complete loss of allosteric coupling, disruption of the disorder-to-order transitions at both functional sites, and a decreased affinity for the effector. In this work, allosteric communication between the effector binding and dimerization surfaces in BirA was further investigated by performing isothermal titration calorimetry measurements on nine proteins with alanine substitutions in three dimerization surface loops. In contrast to BirAG142A, at 20 degrees C all variants bind to bio-5'-AMP with free energies indistinguishable from that measured for wild-type BirA. However, the majority of the variants exhibit altered heat capacity changes for effector binding. Moreover, the DeltaCp values correlate with the dimerization free energies of the effector-bound proteins. These thermodynamic results, combined with structural information, indicate that allosteric activation of the BirA monomer involves formation of a network of intramolecular interactions on the dimerization surface in response to bio-5'-AMP binding at the distant effector binding site. PMID- 26678379 TI - Complete mitochondrial genome of black-banded trevally (Seriolina nigrofasciata): Genome characterization and phylogenetic considerations. AB - The black-banded trevally (Seriolina nigrofasciata) is a species of the family Carangidae and the only known member of genus Seriolina. To understand the phylogenetic relationship of black-banded trevally in teleost, we first determined the complete mitochondrial genome of black-banded trevally. The entire mitochondrial genome of black-banded trevally is 16 531 bp in length, containing 13 protein-coding genes and 2 ribosomal RNA genes (rRNA), 22 transfer RNA genes (tRNAs), and 2 main non-coding regions. The overall base composition is T 25.8%, C 30.0%, A 26.7%, and G 17.5%. The gene arrangement, base composition, and tRNA structures of black-banded trevally are consistent with those of other teleost. Two of the central conserved sequence blocks (CSB-2 and CSB-3) were identified and the core sequence (TACATGTATGTA) of terminal-associated sequences was recognized in the control region. Meanwhile, the conserved motif 5'-GCCGG-3' was identified in the origin of light-strand replication of black-banded trevally. The complete mitochondrial genome of black-banded trevally was used to construct phylogenetic tree, which shows that black-banded trevally is clustered with the fishes of the genus Seriola. We expect that the availability of the mitochondrial genome of black-banded trevally will facilitate the further investigations of molecular systematic and phylogenetic analysis of the Carangidae. PMID- 26678380 TI - Body mass index and human sperm quality: neither one extreme nor the other. AB - The aim of the present study was to investigate the still contentious association between body mass index (BMI) and seminal quality. To this end, 4860 male patients (aged 18-65 years; non-smokers and non-drinkers), were classified according to BMI as either underweight (UW; BMI <20kgm-2; n=45), normal weight (NW; BMI 20-24.9kgm-2; n=1330), overweight (OW; BMI 25-29.9kgm-2; n=2493), obese (OB; BMI 30-39.9kgm-2; n=926) or morbidly obese (MOB; BMI >=40kgm-2; n=57). Conventional semen parameters and seminal concentrations of fructose, citric acid and neutral alpha-glucosidase (NAG) were evaluated. The four parameters that reflect epididymal maturation were significantly lower in the UW and MOB groups compared with NW, OW and OB groups: sperm concentration, total sperm count (103.3+/-11.4 and 121.5+/-20.6 and vs 157.9+/-3.6, 152.4+/-2.7 or 142.1+/-4.3 spermatozoa ejaculate-1 respectively, P<0.05), motility (41.8+/-2.5 and 42.6+/ 2.6 vs 47.8+/-0.5, 48.0+/-0.4 or 46.3+/-0.6 % of motile spermatozoa respectively, P<0.05) and NAG (45.2+/-6.6 and 60.1+/-7.9 vs 71.5+/-1.9, 64.7+/-1.3 or 63.1+/ 2.1 mU ejaculate-1 respectively, P<0.05). Moreover, the percentage of morphologically normal spermatozoa was decreased in the MOB group compared with the UW, NW, OW and OB groups (4.8+/-0.6% vs 6.0+/-0.8%, 6.9+/-0.1%, 6.8+/-0.1 and 6.4+/-0.2%, respectively; P<0.05). In addition, men in the MOB group had an increased risk (2.3- to 4.9-fold greater) of suffering oligospermia and teratospermia (P<0.05). Both morbid obesity and being underweight have a negative effect on sperm quality, particularly epididymal maturation. These results show the importance of an adequate or normal bodyweight as the natural best option for fertility, with both extremes of the BMI scale as negative prognostic factors. PMID- 26678381 TI - The American Society for Clinical Pharmacology and Therapeutics (ASCPT)--A Rich Heritage En Route to an Exciting Future. PMID- 26678382 TI - cgpPindel: Identifying Somatically Acquired Insertion and Deletion Events from Paired End Sequencing. AB - cgpPindel is a modified version of Pindel that is optimized for detecting somatic insertions and deletions (indels) in cancer genomes and other samples compared to a reference control. Post-hoc filters remove false positive calls, resulting in a high-quality dataset for downstream analysis. This unit provides concise instructions for both a simple 'one-shot' execution of cgpPindel and a more detailed approach suitable for large-scale compute farms. PMID- 26678383 TI - VAGrENT: Variation Annotation Generator. AB - VAGrENT is a tool that provides biological context and effect prediction for genomic sequence variants. It annotates single base substitutions and small insertions and deletions by comparing them to reference information within or close to genes or other transcribed elements. This information provides the critical insight required to inform the biological or clinical significance of variant data generated from sequencing studies. The software has been optimized to run efficiently against the large numbers and diverse classes of variants that are typically generated from next generation sequencing technologies. This unit describes how to configure and use VAGrENT and also contains support protocols for extending and adapting its default behavior. PMID- 26678384 TI - iRegulon and i-cisTarget: Reconstructing Regulatory Networks Using Motif and Track Enrichment. AB - Gene expression profiling is often used to identify genes that are co-expressed in a biological process or disease. Downstream analyses of co-expressed gene sets using bioinformatics methods can reveal candidate transcription factors (TF) that co-regulate these genes, based on the presence of shared TF binding sites. Drawing gene regulatory networks that connect TFs to their predicted target genes can uncover gene modules that implement a particular function. Here, we describe several protocols to analyze any set of co-expressed genes using iRegulon and i cisTarget. These tools perform regulatory sequence analysis (motif discovery) and integrate and mine large collections of existing regulatory data, such as ChIP Seq, DHS-seq, and FAIRE-seq (track discovery). While iRegulon focuses on sets of co-expressed genes, i-cisTarget also analyses genomic regions as input. The following protocols describe how to install and use these tools, how to interpret the obtained results, and will thus help to create meaningful regulatory networks. PMID- 26678385 TI - An Introduction to Genome Annotation. AB - Genome projects have evolved from large international undertakings to tractable endeavors for a single lab. Accurate genome annotation is critical for successful genomic, genetic, and molecular biology experiments. These annotations can be generated using a number of approaches and available software tools. This unit describes methods for genome annotation and a number of software tools commonly used in gene annotation. PMID- 26678387 TI - Complete chloroplast genome sequence of Castanopsis concinna (Fagaceae), a threatened species from Hong Kong and South-Eastern China. AB - The complete chloroplast genome of Castanopsis concinna (Champion ex Bentham) A. de Candolle, an endemic species to Hong Kong and southeastern China, was determined in this study. Due to logging, historical habitat loss, and fragmentation, conservation efforts for C. concinna are becoming increasingly urgent as the species is now known from only a handful of locations. To aid efforts to preserve and propagate the species ex situ, knowledge on the distribution of genetic diversity in the remaining populations is crucial. Here we report the complete chloroplast genome sequence of one individual collected in Hong Kong in 2014. The total genome size was 160 606 bp in length, containing a pair of inverted repeats (IRs) of 25 677 bp, which were separated by a large single copy (LSC) and small single copy (SSC) of 90 368 and 18 884 bp, respectively. The overall GC content of the plastid genome was 36.8%. 136 genes were annotated, including 82 protein-coding genes, 46 tRNA genes and 8 rRNA genes. In these genes, 13 contained one or two introns. PMID- 26678386 TI - Protein Structure and Function Prediction Using I-TASSER. AB - I-TASSER is a hierarchical protocol for automated protein structure prediction and structure-based function annotation. Starting from the amino acid sequence of target proteins, I-TASSER first generates full-length atomic structural models from multiple threading alignments and iterative structural assembly simulations followed by atomic-level structure refinement. The biological functions of the protein, including ligand-binding sites, enzyme commission number, and gene ontology terms, are then inferred from known protein function databases based on sequence and structure profile comparisons. I-TASSER is freely available as both an on-line server and a stand-alone package. This unit describes how to use the I TASSER protocol to generate structure and function prediction and how to interpret the prediction results, as well as alternative approaches for further improving the I-TASSER modeling quality for distant-homologous and multi-domain protein targets. PMID- 26678388 TI - Dietary Patterns and Chronic Obstructive Pulmonary Disease: A Meta-analysis. AB - Investigation of the relationship between dietary patterns and some chronic noncommunicable diseases has become appealing in nutritional epidemiology. Some studies have reported potential associations between dietary patterns and the risk of chronic obstructive pulmonary disease; however, the results remain conflicting. Thus, we conducted this meta-analysis to pool the results of studies to clarify the associations between dietary patterns and the risk of chronic obstructive pulmonary disease. A literature search of MEDLINE and EBSCO databases was performed to identify relevant studies published from January 1990 up to June 2015. A total of 13 studies met the inclusion criteria and were included in this meta-analysis. The highest category of healthy/prudent dietary patterns when compared with the lowest category was apparently associated with a decreased risk (OR = 0.55; CI: 0.46, 0.66; P < 0.0001). An increase in the risk of chronic obstructive pulmonary disease was shown for the highest compared with the lowest categories of "unhealthy/western-style" dietary patterns (OR = 2.12; CI: 1.64, 2.74; P < (0.0001). The results of this meta-analysis indicate that different dietary pattern may be associated with the risk of chronic obstructive pulmonary disease. PMID- 26678389 TI - Correction: Species-Specific Codon Context Rules Unveil Non-Neutrality Effects of Synonymous Mutations. PMID- 26678390 TI - Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running. AB - In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life. PMID- 26678392 TI - 35,000 Days on Earth. PMID- 26678391 TI - Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia. AB - The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated. PMID- 26678394 TI - Darbepoetin-alpha Promotes Cell Proliferation in Established Extrahepatic Colorectal Tumors after Major Hepatectomy. AB - BACKGROUND: The glycoprotein hormone erythropoietin and its analogue darbepoetin alpha (DPO) have been shown to reduce the risk of acute liver failure after major hepatectomy. However, previous experimental studies have also shown that DPO significantly enhances neovascularization and tumor cell proliferation in established colorectal liver metastasis in hepatectomized and nonhepatectomized mice. The present study now analyzes whether DPO influences cell proliferation and migration as well as vascularization and growth of established colorectal metastasis at extrahepatic sites after major hepatectomy. METHODS: GFP transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Five days after tumor cell implantation, the animals received a single dose of DPO (10 ug/kg body weight) or phosphate buffered saline solution (PBS) intravenously. Additional animals received a 70% hepatectomy and DPO or PBS treatment. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry. RESULTS: DPO did not influence tumor cell migration and apoptosis. In addition, DPO did not stimulate tumor cell infiltration or vascularization; however, significantly increased tumor cell proliferation was detected in hepatectomized animals. CONCLUSION: DPO increases cell proliferation in established extrahepatic colorectal metastases after major hepatectomy. Thus, DPO may not be recommended to stimulate regeneration of the remnant liver after major hepatectomy for colorectal liver metastasis. PMID- 26678393 TI - Earth Observation, Spatial Data Quality, and Neglected Tropical Diseases. AB - Earth observation (EO) is the use of remote sensing and in situ observations to gather data on the environment. It finds increasing application in the study of environmentally modulated neglected tropical diseases (NTDs). Obtaining and assuring the quality of the relevant spatially and temporally indexed EO data remain challenges. Our objective was to review the Earth observation products currently used in studies of NTD epidemiology and to discuss fundamental issues relating to spatial data quality (SDQ), which limit the utilization of EO and pose challenges for its more effective use. We searched Web of Science and PubMed for studies related to EO and echinococossis, leptospirosis, schistosomiasis, and soil-transmitted helminth infections. Relevant literature was also identified from the bibliographies of those papers. We found that extensive use is made of EO products in the study of NTD epidemiology; however, the quality of these products is usually given little explicit attention. We review key issues in SDQ concerning spatial and temporal scale, uncertainty, and the documentation and use of quality information. We give examples of how these issues may interact with uncertainty in NTD data to affect the output of an epidemiological analysis. We conclude that researchers should give careful attention to SDQ when designing NTD spatial-epidemiological studies. This should be used to inform uncertainty analysis in the epidemiological study. SDQ should be documented and made available to other researchers. PMID- 26678396 TI - "My pet has passed": Relations of adult attachment styles and current feelings of grief and trauma after the event. AB - This study examined attachment relationships and emotional distress after the passing of a pet. Participants were 73 university students 17-26 years of age who had lost a family pet within the past 5 years. They completed measures of attachment styles toward people and their pet, as well as complicated grief, depression, and trauma. As hypothesized, there were positive relations between attachments with people and pets, and anxiety in pet attachment was positively related to complicated grief, even when attachment with people was controlled. Results are discussed in terms of the importance of attachment style to grief over loss. PMID- 26678395 TI - A Novel Bispecific Antibody against Human CD3 and Ephrin Receptor A10 for Breast Cancer Therapy. AB - Ephrin receptor A10 (EphA10), a transmembrane receptor that binds to ephrin, is a newly identified breast cancer marker protein that has also been detected in HER2 negative tissue. In this study, we report creation of a novel bispecific antibody (BsAb) binding both EphA10 and CD3, thereby forming a bridge between antigens expressed on both tumor and immune cells and promoting recognition of tumor cells by immune cells and redirection of cytotoxic T cells (CTL). This BsAb (EphA10/CD3) was expressed in supernatants of BsAb gene-transfected cells as monomeric and dimeric molecules. Redirected T-cell lysis was observed when monomeric and dimeric BsAb were added to EphA10-overexpressing tumor cells in vitro. Furthermore, dimeric BsAb (EphA10/CD3) was more cytotoxic than monomeric BsAb, with efficient tumor cell lysis elicited by lower concentrations (<=10(-1) MUg/mL) and a lower effector to target (E/T) cell ratio (E/T = 2.5). Dimeric BsAb (EphA10/CD3) also showed significant anti-tumor effects in human xenograft mouse models. Together, these results revealed opportunities to redirect the activity of CTL towards tumor cells that express EphA10 using the BsAb (EphA10/CD3), which could be tested in future clinical trials as a novel and potent therapeutic for breast cancer tumors. PMID- 26678397 TI - Effects of hydro-alcoholic extract of Launaea acanthodes on serum gonadotropin and testosterone levels and the structure of seminiferous tubules in hyperglycemic rats. AB - OBJECTIVE: To investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats. METHODS: Twenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg*day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg*day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques. RESULTS: In comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01). CONCLUSIONS: Administration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects. PMID- 26678398 TI - The Effectiveness of Self-regulatory Speech Training for Planning and Problem Solving in Children with Specific Language Impairment. AB - Self-regulatory speech has been shown to be important for the planning and problem solving of children. Our intervention study, including comparisons to both wait-list and typically developing controls, examined the effectiveness of a training programme designed to improve self-regulatory speech, and consequently, the planning and problem solving performance of 87 (60 males, 27 females) children aged 4-7 years with Specific Language Impairment (SLI) who were delayed in their self-regulatory speech development. The self-regulatory speech and Tower of London (TOL) performance of children with SLI who received the intervention initially or after a waiting period was compared with that of 80 (48 male, 32 female) typically developing children who did not receive any intervention. Children were tested at three time points: Time 1- prior to intervention; Time 2 after the first SLI group had received training and the second SLI group provided a wait-list control; and Time 3 - when the second SLI group had received training. At Time 1 children with SLI produced less self-regulatory speech and were impaired on the TOL relative to the typically developing children. At Time 2, the TOL performance of children with SLI in the first training group improved significantly, whereas there was no improvement for the second training group (the wait-list group). At Time 3, the second training group improved their TOL performance and the first group maintained their performance. No significant differences in TOL performance were evident between typically developing children and those with SLI at Time 3. Moreover, decreases in social speech and increases in inaudible muttering following self-regulatory speech training were associated with improvements in TOL performance. Together, the results show that self regulatory speech training was effective in increasing self-regulatory speech and in improving planning and problem solving performance in children with SLI. PMID- 26678399 TI - Effects of a Brief Psychoeducational Intervention for Family Conflict: Constructive Conflict, Emotional Insecurity and Child Adjustment. AB - The role of emotional security in promoting positive adjustment following exposure to marital conflict has been identified in a large number of empirical investigations, yet to date, no interventions have explicitly addressed the processes that predict child adjustment after marital conflict. The current study evaluated a randomized controlled trial of a family intervention program aimed at promoting constructive marital conflict behaviors thereby increasing adolescent emotional security and adjustment. Families (n = 225) were randomized into 1 of 4 conditions: Parent-Adolescent (n = 75), Parent-Only (n = 75), Self-Study (n = 38) and No Treatment (n = 37). Multi-informant and multi-method assessments were conducted at baseline, post-treatment and 6-month follow-up. Effects of treatment on destructive and constructive conflict behaviors were evaluated using multilevel models where observations were nested within individuals over time. Process models assessing the impact of constructive and destructive conflict behaviors on emotional insecurity and adolescent adjustment were evaluated using path modeling. Results indicated that the treatment was effective in increasing constructive conflict behaviors (d = 0.89) and decreasing destructive conflict behaviors (d = -0.30). For the Parent-Only Group, post-test constructive conflict behaviors directly predicted lower levels of adolescent externalizing behaviors at 6-month follow-up. Post-test constructive conflict skills also indirectly affected adolescent internalizing behaviors through adolescent emotional security. These findings support the use of a brief psychoeducational intervention in improving post-treatment conflict and emotional security about interparental relationships. PMID- 26678400 TI - Material-specific retroactive interference effects of the Wechsler Adult Intelligence Scale-Fourth Edition on the Wechsler Memory Scale-Fourth Edition in a nonclinical sample. AB - INTRODUCTION: This study investigated proactive and retroactive interference effects between the Wechsler Memory Scale-Fourth Edition (WMS-IV) using the flexible approach, and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS IV). METHOD: One hundred and eighty nonclinical participants were assigned to a four (visual interference, verbal interference, visual and verbal interference, vs. no interference) by two (retroactive vs. proactive) between-subjects design. The administration order of the tests was counterbalanced (i.e., administration of the WAIS-IV prior to the WMS-IV, and the WAIS-IV administered during the delay interval of the WMS-IV). RESULTS: The WAIS-IV produced significant retroactive interference effects on the WMS-IV; however, no proactive interference effect was observed. The retroactive interference effect was dependent on material specificity. CONCLUSIONS: The results indicate that material presented within the delay of the WMS-IV can have a significant effect on subsequent delayed recall. Clinicians should carefully consider the effects associated with carry-over effects of these tests when using them in combination. PMID- 26678401 TI - In reply: Sevoflurane or desflurane: Which one is more expensive? Limiting the accessibility of cost-prohibitive drugs: The story is incomplete. PMID- 26678402 TI - Social pain and physical pain: shared paths to resilience. AB - Although clinical models have traditionally defined pain by its consequences for the behavior and internal states of the sufferer, recent evidence has highlighted the importance of examining pain in the context of the broader social environment. Neuroscience research has highlighted commonalities of neural pathways connecting the experience of physical and social pain, suggesting a substantial overlap between these phenomena. Further, interpersonal ties, support and aspects of the social environment can impair or promote effective adaptation to chronic pain through changes in pain perception, coping and emotional states. The current paper reviews the role of social factors in extant psychological interventions for chronic pain, and discusses how greater attention to these factors may inform future research and clinical care. PMID- 26678403 TI - The Evolving Profile of the Signature Amino Acid Residues in HIV-1 Subtype C Tat. AB - Using several HIV-1 tat exon 1 amino acid sequences available from public databases and additional sequences derived from a southern Indian clinical cohort, we compared the profile of the signature amino acid residues (SAR) between two different time periods, 1986-2004 and 2005-2014. The analysis identified eight positions as signature residues in subtype C Tat and demonstrated a changing pattern at four of these positions between the two periods. At three locations (histidine 29, serine 57, and proline 60), there appears to be a nonuniform negative selection against the SAR. The negative selection appears to be severe, especially against histidine 29 (p < .0001) and moderate against proline 60 (p < .0001). The negative selection against serine 57 is statistically insignificant and appears to have begun recently. At position 63, the frequency of signature residue glutamic acid increased over the past decade, although the difference was not significant. Importantly, at the three locations where the negative selection is in progress, the substitute amino acids are the generic residues present in most of the other HIV-1 subtypes. Our data demonstrate that viral evolution can subject specific amino acid residues to subtle and progressive selection pressures without affecting the prevalence of other amino acid residues. PMID- 26678404 TI - Can a Benefit be Expected from Surgical Debulking of Unresectable Pseudomyxoma Peritonei? AB - PURPOSE: This study evaluated the role of surgical debulking in improving pseudomyxoma peritonei (PMP)-related symptoms if complete cytoreductive surgery (CCRS) of huge PMP is unachievable. METHODS: This was a retrospective analysis of a prospective database of all patients in our tertiary care center treated for PMP between 1992 and 2014. All cases of surgical debulking in patients scheduled for CCRS that proved unachievable during the operation were selected for the present study. RESULTS: Among the 338 patients operated on for PMP, 39 (11.5 %) had undergone surgical debulking because CCRS was unachievable. All of these patients were symptomatic before surgery, and the median PCI was 32 (5-39). More than 80 % of the disease burden was resected in 23 patients (59 %). Mortality and major morbidity rates were 2.5 and 23 %, respectively. After debulking surgery, symptoms gradually subsided over a median time of 23 months and 50 % of the patients no longer experienced PMP-related symptoms after a median follow-up of 24.5 months. After a median follow-up of 46.4 months (range 3-120), median overall (OS) and progression-free (PFS) survival times were 55.5 and 20 months, respectively. Five-year OS and PFS rates were 46 and 11 %, respectively. CONCLUSIONS: Aggressive debulking surgery in case of unachievable CCRS for huge PMP can offer prolonged relief of PMP-related symptoms and long-term survival, in experienced centers that are able to be sufficiently aggressive to resect the major part of the disease, and conservative enough to achieve low mortality and good quality of life. PMID- 26678405 TI - Impact of Time from Completion of Neoadjuvant Chemotherapy to Surgery on Survival Outcomes in Breast Cancer Patients. AB - BACKGROUND: No studies have examined the impact of the interval from conclusion of neoadjuvant chemotherapy to surgery in breast cancer patients. This study was undertaken to investigate the relationship between time interval from neoadjuvant chemotherapy to surgery and survival outcomes. METHODS: Breast cancer patients diagnosed with stage I-III disease who received neoadjuvant chemotherapy June 1995 to April 2007 were identified. The effect of neoadjuvant chemotherapy to surgery interval, defined as <=4, 4-6, or >6 weeks, on survival outcomes was examined. Descriptive statistics and Cox proportional hazards models were used. RESULTS: A total of 1101 patients were identified. Median time to surgery was 33 (range 8-159) days; 335 patients (30.4 %) had surgery within 4 weeks of their last dose of neoadjuvant chemotherapy, 524 (47.6 %) within 4-6 weeks, and 242 (22.0 %) after more than 6 weeks. Median follow-up was 94 (range 3-178) months. The 5-year overall survival (OS) estimates were 79, 87, and 81 % in patients who underwent surgery <=4, 4-6, and >6 weeks after neoadjuvant chemotherapy, respectively (p = 0.03). The three groups did not differ in 5-year recurrence free survival (RFS) or locoregional recurrence-free survival (LRFS). In multivariable analysis, compared with an interval of <=4 weeks, patients who underwent surgery at 4-6 or >6 weeks had equivalent OS, LRFS, and RFS; a sensitivity analysis suggested worse OS in patients who underwent surgery at >8 weeks. CONCLUSIONS: Patients with neoadjuvant chemotherapy to surgery intervals of up to 8 weeks had equivalent OS, RFS, and LRFS. PMID- 26678407 TI - Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma: A Nordic Multicenter Comparative Study. AB - BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery is uncertain. METHODS: Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan-Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate factors potentially influencing survival. RESULTS: The study registered 119 patients. The median survival period from the time of metastasis was 23 months for patients undergoing initial resection of localized nonmetastatic disease and chemotherapy at the time of recurrence (n = 14), 29 months for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor and metastatic disease was 69 %. Resection of the primary tumor was an independent factor for improved survival after occurrence of metastatic disease. CONCLUSIONS: Patients with resected localized nonmetastatic hgPNEC and later metastatic disease seemed to benefit from initial resection of the primary tumor. Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment. PMID- 26678406 TI - A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy. AB - BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has an emerging role in the treatment of peritoneal malignancies. The CRS-HIPEC approach has known treatment-related toxicities. This study sought to determine the predictors of major postoperative complications after CRS-HIPEC in a high-volume center. METHODS: From a single-institution database, this study investigated complications experienced by patients undergoing CRS-HIPEC. Multiple preoperative and operative factors were analyzed for their ability to predict 60 day Clavien grade 3 and greater (major) complications by logistic regression. A predictive model was created from preoperative factors using multivariate logistic regression. The model was tested by Akaike's information criterion, the Hosmer and Lemeshow Goodness-of-Fit Test, the receiver operating characteristic, and the Youden Index. RESULTS: The study evaluated 247 patients undergoing CRS HIPEC. The primary tumor site was the appendix in 166 cases (67.2 %), the colorectal area in 51 cases (20.6 %), the peritoneum (mesothelioma) in 22 cases (8.9 %), the ovary in 5 cases (2 %), and the small bowel in 3 cases (1.2 %). The median peritoneal cancer index was 14 (range 0-29), and 235 patients (95.1 %) had a complete (CC-0/1) cytoreduction. Major complications occurred for 41 patients (16.6 %), classified as grade 3 in 33 cases (13.4 %), grade 4 in 5 cases (2 %), and grade 5 (deaths) in 3 cases (1.2 %). The factors predictive of major complications in the multivariate analysis were a Charlson Comorbidity Index (CCI) score higher than 0 [odds ratio (OR), 2.505; p = 0.035], presence of preoperative symptoms (OR 1.951; p = 0.064), and prior resection status [no resection or prior CRS-HIPEC (OR 2.087) vs. prior resection without CRS-HIPEC (OR 3.209); p = 0.046]. These variables were used to create a tool predictive of postoperative complications. CONCLUSION: Presence of symptoms, CCI, and prior resection status predict major complications and define a low-risk population after CRS-HIPEC. PMID- 26678408 TI - Subset selection of high-depth next generation sequencing reads for de novo genome assembly using MapReduce framework. AB - BACKGROUND: Recent progress in next-generation sequencing technology has afforded several improvements such as ultra-high throughput at low cost, very high read quality, and substantially increased sequencing depth. State-of-the-art high throughput sequencers, such as the Illumina MiSeq system, can generate ~15 Gbp sequencing data per run, with >80% bases above Q30 and a sequencing depth of up to several 1000x for small genomes. Illumina HiSeq 2500 is capable of generating up to 1 Tbp per run, with >80% bases above Q30 and often >100x sequencing depth for large genomes. To speed up otherwise time-consuming genome assembly and/or to obtain a skeleton of the assembly quickly for scaffolding or progressive assembly, methods for noise removal and reduction of redundancy in the original data, with almost equal or better assembly results, are worth studying. RESULTS: We developed two subset selection methods for single-end reads and a method for paired-end reads based on base quality scores and other read analytic tools using the MapReduce framework. We proposed two strategies to select reads: MinimalQ and ProductQ. MinimalQ selects reads with minimal base-quality above a threshold. ProductQ selects reads with probability of no incorrect base above a threshold. In the single-end experiments, we used Escherichia coli and Bacillus cereus datasets of MiSeq, Velvet assembler for genome assembly, and GAGE benchmark tools for result evaluation. In the paired-end experiments, we used the giant grouper (Epinephelus lanceolatus) dataset of HiSeq, ALLPATHS-LG genome assembler, and QUAST quality assessment tool for comparing genome assemblies of the original set and the subset. The results show that subset selection not only can speed up the genome assembly but also can produce substantially longer scaffolds. AVAILABILITY: The software is freely available at https://github.com/moneycat/QReadSelector. PMID- 26678409 TI - Corrigendum. PMID- 26678410 TI - A scoping review of the experiences, benefits, and challenges involved in volunteer work among youth and young adults with a disability. AB - PURPOSE: To develop a better understanding of the experiences of volunteer work among youth with disabilities. METHOD: A scoping review was undertaken to assess the benefits and challenges of volunteering among youth with disabilities. Comprehensive searches using six international databases were conducted. Eligible articles included: (a) youth aged 30 or younger, with a disability; (b) empirical research on the benefits or challenges of volunteering; (c) published in a peer reviewed journal between 1980 and 2014. RESULTS: Of the 1558 articles identified, 20 articles - involving 1409 participants, aged 12-30, across five countries - met the inclusion criteria. Studies linked volunteering to the development of human capital (i.e. practical experience, improved self-determination, self confidence, coping), enhanced social capital (i.e. social and communication skills, social inclusion) and improved cultural capital (i.e. helping others, contributing to community). Many youth with disabilities also encountered challenges - including lack of accessible volunteer opportunities, difficulties arranging transportation, and negative attitudes from potential supervisors. CONCLUSIONS: Young people with disabilities are willing and able to volunteer, and they report benefits of volunteering; however, they face many challenges in finding suitable volunteer positions. More rigorous research is needed to understand the health and social benefits of volunteering and how it can help youth develop career pathways. Implications for Rehabilitation Clinicians, educators and parents should discuss the benefits of volunteering with youth with disabilities and assist them in finding placements that match their interests and abilities. Managers and clinicians should consider incorporating volunteering into vocational rehabilitation programming (i.e. addressing how to find placements and connecting youth to organisations). Clinicians should encourage youth to take part in social and extracurricular activities to help build their social skills and networks where they can learn about volunteer opportunities. Clinicians and educators should advocate on behalf of youth with disabilities among community organisations to help break down barriers and reduce misconceptions and negative attitudes by showcasing the abilities that youth with disabilities have to offer. PMID- 26678411 TI - Analysis of genomic rearrangements by using the Burrows-Wheeler transform of short-read data. AB - BACKGROUND: The potential utility of the Burrows-Wheeler transform (BWT) of a large amount of short-read data ("reads") has not been fully studied. The BWT basically serves as a lossless dictionary of reads, unlike the heuristic and lossy reads-to-genome mapping results conventionally obtained in the first step of sequence analysis. Thus, it is naturally expected to lead to development of sensitive methods for analysis of short-read data. Recently, one of the most active areas of research in sequence analysis is sensitive detection of rare genomic rearrangements from whole-genome sequencing (WGS) data of heterogeneous cancer samples. The application the BWT of reads to the analysis of genomic rearrangements is addressed in this study. RESULTS: A new method for sensitive detection of genomic rearrangements by using the BWT of reads in the following three steps is proposed: first, breakpoint regions, which contain breakpoints and are joined together by rearrangement, are predicted from the distribution of so called discordant pairs by using a kind of the conjugate gradient method; second, reads partially matching the breakpoint regions are collected from the BWT of reads; and third, breakpoints are detected as branching points among the collected reads, and their precise positions are determined. The method was experimentally implemented, and its performance (i.e., sensitivity and specificity) was evaluated by using simulated data with known artificial rearrangements. It was applied to publicly available real biological WGS data of cancer patients, and the detection results were compared with published results. CONCLUSIONS: Serving as a lossless dictionary of reads, the BWT of short reads enables sensitive analysis of genomic rearrangements in heterogeneous cancer genome samples when used in conjunction with breakpoint-region predictions based on a conjugate gradient method. PMID- 26678412 TI - Cooperation of German ophthalmologists in routine care of patients with neovascular age-related macular degeneration: results of the non-interventional BRIDGE study. AB - PURPOSE: In the non-interventional ophthalmological study 'BRIDGE' the routine care of patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab was observed in Germany. A patient regularly sees the general ophthalmologist (GO) for monitoring and, if needed, the injecting ophthalmologist (IO) for intravitreal injections (IVI). Thus, patients are routinely treated by two ophthalmologists in parallel and patient care depends on their collaboration. This cooperation was evaluated based on network questionnaires. METHODS: 'BRIDGE' was a multicenter, national, open-label, prospective, observational study, conducted between July 2010 and December 2012. The network questionnaire for GOs consisted of 51 questions, while the similar questionnaire for IOs consisted of 43 questions, addressing the type and details of the individual collaboration. The statistical analysis was purely descriptive. RESULTS: The network questionnaire for GOs was completed by 152 GOs, regularly cooperating with 2.5 +/ 1.1 IOs, while the questionnaire for IOs was completed by 43 IOs, regularly cooperating with 23.2 +/- 23.6 GOs. Generally, both GOs and IOs stated that they regularly exchange information regarding the patients' situation. Diagnostic standards were only established for 15 % of the GOs' collaborations and for 35 % of the IOs' collaborations. After initial treatment, both GOs and IOs agreed on the medical significance of regular monitoring visits performed by the GOs. Agreements on re-treatment criteria were only established in the case of 16 % of the GOs and 28 % of the IOs. Overall, both GOs and IOs were satisfied with the current situation, with regard to the medical treatment situation for patients and to the cooperation within the networks. CONCLUSIONS: The network questionnaires revealed well-established cooperation between IOs and GOs in Germany with an accepted division of responsibilities for the routine care of patients with nAMD. However, the cooperation between two ophthalmologists treating one patient harbors risks. Agreements on diagnostic and re-treatment criteria would help to improve network performance and outcomes. PMID- 26678414 TI - Notes from the Field: Injection Safety and Vaccine Administration Errors at an Employee Influenza Vaccination Clinic--New Jersey, 2015. AB - On September 30, 2015, the New Jersey Department of Health (NJDOH) was notified by an out-of-state health services company that an experienced nurse had reused syringes for multiple persons earlier that day. This occurred at an employee influenza vaccination clinic on the premises of a New Jersey business that had contracted with the health services company to provide influenza vaccinations to its employees. The employees were to receive vaccine from manufacturer-prefilled, single-dose syringes. However, the nurse contracted by the health services company brought three multiple-dose vials of vaccine that were intended for another event. The nurse reported using two syringes she found among her supplies to administer vaccine to 67 employees of the New Jersey business. She reported wiping the syringes with alcohol and using a new needle for each of the 67 persons. One of the vaccine recipients witnessed and questioned the syringe reuse, and brought it to the attention of managers at the business who, in turn, reported the practice to the health services company contracted to provide the influenza vaccinations. PMID- 26678413 TI - Outcomes From Health Information Exchange: Systematic Review and Future Research Needs. AB - BACKGROUND: Health information exchange (HIE), the electronic sharing of clinical information across the boundaries of health care organizations, has been promoted to improve the efficiency, cost-effectiveness, quality, and safety of health care delivery. OBJECTIVE: To systematically review the available research on HIE outcomes and analyze future research needs. METHODS: Data sources included citations from selected databases from January 1990 to February 2015. We included English-language studies of HIE in clinical or public health settings in any country. Data were extracted using dual review with adjudication of disagreements. RESULTS: We identified 34 studies on outcomes of HIE. No studies reported on clinical outcomes (eg, mortality and morbidity) or identified harms. Low-quality evidence generally finds that HIE reduces duplicative laboratory and radiology testing, emergency department costs, hospital admissions (less so for readmissions), and improves public health reporting, ambulatory quality of care, and disability claims processing. Most clinicians attributed positive changes in care coordination, communication, and knowledge about patients to HIE. CONCLUSIONS: Although the evidence supports benefits of HIE in reducing the use of specific resources and improving the quality of care, the full impact of HIE on clinical outcomes and potential harms are inadequately studied. Future studies must address comprehensive questions, use more rigorous designs, and employ a standard for describing types of HIE. TRIAL REGISTRATION: PROSPERO Registry No CRD42014013285; http://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42014013285 (Archived by WebCite at http://www.webcitation.org/6dZhqDM8t). PMID- 26678415 TI - The privatization of medical education in Brazil: trends and challenges. AB - BACKGROUND: Like other countries, Brazil is struggling with issues related to public policies designed to influence the distribution, establishment, supply and education of doctors. While the number of undergraduate medical schools and places available on medical schools has risen, the increase in the number of doctors in Brazil in recent decades has not benefitted the population homogeneously. The government has expanded the medical schools at the country's federal universities, while providing incentives for the creation of new undergraduate courses at private establishments. This article examines the trends and challenges of the privatization of medical education in Brazil. METHODS: This is a descriptive, cross-sectional study based on secondary data from official government databases on medical schools and courses and institutions offering such courses in Brazil. It takes into account the year when the medical schools received authorization to initiatte the activities, where they are situated, whether they are run by a public or private entity, how many places they offer, how many students they have enrolled, and their performance according to Ministry of Education evaluations. RESULTS: Brazil had 241 medical schools in 2014, offering a total of 20,340 places. The private higher education institutions are responsible for most of the enrolment of medical students nationally (54 %), especially in the southeast. However, enrolment in public institutions predominate more in the capitals than in other cities. Overal, the public medical schools performed better than the private schools in the last two National Exam of Students' (ENADE). CONCLUSION: The privatization of the teaching of medicine at undergraduate level in Brazil represents a great challenge: how to expand the number of places while assuring quality and democratic access to this form of education. Upon seeking to understand the configuration and trends in medical education in Brazil, it is hoped that this analysis may contribute to a broader research agenda in the future. PMID- 26678417 TI - Identifying early signs of peripheral neuropathy among patients with diabetes mellitus. AB - This article aims to help nurse practitioners develop a best practice algorithm to identify the early signs of peripheral neuropathy (PNP) among individuals living with diabetes mellitus. This literature review also seeks to determine if there are better clinical testing methods than the Semmes-Weinstein monofilament examination to detect diabetes-related PNP. PMID- 26678416 TI - Effects of electrical stimulation on rat limb regeneration, a new look at an old model. AB - Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body's regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting "blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation". In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs. PMID- 26678418 TI - When to consider acute HIV infection in the differential diagnosis. AB - Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID- 26678419 TI - The 28th Annual APRN Legislative Update: Beyond the 50 states. PMID- 26678420 TI - The "staring" child. PMID- 26678422 TI - 28th Annual APRN Legislative Update: Advancements continue for APRN practice. AB - The Annual Legislative Update discusses the legislative accomplishments in the areas of practice authority, reimbursement, and prescriptive authority that have the most impact on nurse practitioners and other advanced practice nurses across the country. PMID- 26678423 TI - Cannabis for posttraumatic stress disorder: A neurobiological approach to treatment. AB - The endocannabinoid system is intricately involved in regulation of the neurobiological processes, which underlie the symptomatology of posttraumatic stress disorder (PTSD). This article discusses the neurobiological underpinnings of PTSD and the use of cannabis for treating PTSD in the New Mexico Medical Cannabis Program. PMID- 26678425 TI - TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3'UTR affecting viral RNAs accumulation and symptom expression. AB - The upstream pseudoknots domain (UPD) of Tobacco mosaic virus (TMV) is located at the 3'-untranslated region (UTR). It plays an important role in virus replication and translation. To determine the importance of UPD and 3'-UTR, and the effects of introduced RNA elements in TMV 3'-UTR, a series of TMV mutants with internal poly(A) tract upstream of UPD was constructed for structural analysis by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). TMV(24A+UPD) and TMV(42A+UPD) formed a similar structure as that of TMV 3'-UTR, but TMV(62A+UPD) structures altered by the introduced poly(A) tract. In addition, TMV(24A+UPD) had a higher viral RNAs accumulation than TMV in N. benthamiana protoplasts, and induced lethal symptoms in the infected plants. TMV(62A+UPD) showed a drastically reduced accumulation, its coat protein was undetectable in protoplasts, and the inoculated plants remained symptomless. This study analyzed the structures of 3'-UTR of TMV and found that the longer poly(A) tract introduced upstream of UPD reduced viral RNAs accumulation and induced milder symptoms in N. benthamiana. In conclusion, different lengths of the internal poly(A) tract introduced into the TMV 3'UTR lead to structural variations that affect virus accumulation and symptom expression. PMID- 26678426 TI - Multiplanar CT Analysis of Fifth Metatarsal Morphology: Implications for Operative Management of Zone II Fractures. AB - BACKGROUND: Percutaneous internal fixation is currently the method of choice treating proximal zone II fifth metatarsal fractures. Complications have been reported due to poor screw placement and inadequate screw sizing. The purpose of this study was to define the morphology of the fifth metatarsal to help guide surgeons in selecting the appropriate screw size preoperatively. METHODS: Multiplanar analysis of fifth metatarsal morphology was completed using computed tomographic (CT) scans from 241 patients. Specific parameters were analyzed and defined in anteroposterior (AP), lateral, and oblique views including metatarsal length, distance from the base to apex of curvature, apex medullary canal width, apex height, and fifth metatarsal angle. RESULTS: The average metatarsal length in the AP view was 71.4 +/- 6.1 mm and in the lateral view 70.4 +/- 6.0 mm, with 95% of patients having lengths between 59.3 and 83.5 mm and 58.4 and 82.4 mm, respectively. The average canal width at the apex of curvature was 4.1 +/- 0.9 mm in the AP view and 5.3 +/- 1.1 mm in the lateral view, with 95% of patients having widths between 2.2 and 5.9 mm and 3.2 and 7.5 mm, respectively. Average distance from apex to base was 42.6 +/- 5.8 mm in the AP and 40.4 +/- 6.4 mm in the lateral views. Every measurement taken in all 3 views had a significant correlation with height. CONCLUSIONS: When determining screw length, we believe lateral radiographs should be used since the distance from the base of the metatarsal to the apex was smaller in the lateral view. On average, the screw should be 40 mm or less to reduce risk of distraction. For screw diameter, the AP view should be used because canal shape is elliptical, and width was found to be significantly smaller in the AP view. Most canals can accommodate a 4.0- or 4.5 mm-diameter screw, and one should use the largest diameter screw possible. Larger individuals were likely to have more bowing in their metatarsal shaft, which may lead to a higher tendency to distract. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 26678427 TI - Randomized, Prospective Study of the Order of Preoperative Preparation Solutions for Patients Undergoing Foot and Ankle Orthopedic Surgery. AB - BACKGROUND: Surgical site infection is routinely cited as the most common complication following orthopedic foot and ankle surgery. Our institution uses 4% chlorhexidine gluconate followed by 70% isopropyl alcohol to reduce skin bacterial loads prior to surgery. These solutions have potential synergistic qualities to prevent a postoperative infection. The purpose of this study was to determine if the order of these solutions has a significant effect on the residual bacterial pathogens load following operative site preparation for foot and ankle surgery, as evidenced by positive culture swabs. METHODS: A total of 95 consecutive patients, undergoing surgery of the foot and ankle with a single surgeon, were prospectively randomized to 1 of 2 operative preparation groups: isopropyl alcohol (IPA) group, whose operative site preparation consisted of a 4% chlorhexidine application followed by alcohol rinse (49 patients), and chlorhexidine gluconate (CHG) group, which had 46 patients undergo operative site preparation using alcohol followed by chlorhexidine. A total of 4 aerobic culture specimens were obtained from the third web space of the operative foot on each patient: (1) prior to operative site preparation, (2) after the prep was completed, (3) after completion of the procedure, and (4) after the incision was closed. Each patient was then followed for 6 months postoperatively to monitor the operative site. Medical comorbidities were also analyzed. RESULTS: The average time for IPA procedures was 52 minutes vs 54 for CHG (ns). There was no difference between groups with respect to diabetes, tobacco use, obesity, race, or immunosuppression. Both groups had 100% bacterial growth from specimens obtained prior to operative site preparation (P > .05). For all postpreparation swabs, 19.0% (28/147) of the IPA cultures were positive compared to 10.9% (15/138) from the CHG group cultures (P = .07). The amount of patients with positive culture results favored the CHG group at each collection point: 6.5% (3/46) versus 25% (12/49) after draping (P = .02); 15% (7/46) versus 33% (16/49) after completion of the surgery (P = .05); and 20% (9/46) versus 35% (17/49) after skin closure (P = .07). One operative site infection was seen in the first 30 days following surgery for each treatment group, each treated with oral antibiotics. No additional skin or wound complications were encountered during the 6-month study follow-up. CONCLUSION: Postoperative infection rates following foot and ankle orthopedic surgery was low. Both chlorhexidine and isopropyl alcohol solutions were effective methods in reducing operative site bacterial colonization when combined. In this study, applying isopropyl alcohol solution followed by the chlorhexidine solution was more effective in reducing positive bacterial cultures taken after operative site preparation. No difference in clinical wound infection rate was seen. LEVEL OF EVIDENCE: Level I, prospective randomized study. PMID- 26678428 TI - Implications of observed PBDE diffusion coefficients in low density polyethylene and silicone rubber. AB - A film-stacking technique was used to estimate diffusion coefficients of polybrominated diphenyl ethers (PBDEs) in low density polyethylene (LDPE) and silicone rubber. Substantially higher PBDE diffusion coefficients were observed for silicone rubber (AlteSilTM) than for LDPE. A much steeper decrease in LDPE diffusion coefficients was found with increasing PBDE molecular weight than that for silicone rubber. From a passive sampling point-of-view, this means that for equivalent polymer-water partition coefficients for these two materials, the mass transfer resistance for these substances in the LDPE will be significantly higher than that for silicone rubber. Boundary layer control of the uptake process for silicone rubber can be expected for PBDEs. With a microplastic perspective, the low diffusion coefficients of PBDEs and in particular of decabromo diphenyl ether (BDE 209) in LDPE imply that the polymer diffusion coefficients for these plastic additives used as flame retardants need to be taken into account when considering the risk posed by microplastic particle ingestion by marine organisms. PMID- 26678429 TI - Comparison of oral health behavior among dental students, students of other disciplines, and fashion models in Switzerland. AB - Self-reliant oral health behavior exert great influence on the oral health of our society. The aim of the present study was to find out whether there is an occupation-related difference in the oral health behavior between dental students, students of other disciplines, and fashion models in German-speaking Switzerland. The survey comprised 19 questions which were asked using a web-based anonymous questionnaire. The investigation particularly inquired about employed auxiliaries and their application for an improvement of oral hygiene. In addition, the satisfaction with the own teeth and smile as well as the influence of the occupation or the study on oral hygiene were examined. Included in this evaluation were 204 dental students, 257 students of other disciplines, and 117 fashion models aged between 21 and 25 years. The evaluation reveals that the state of knowledge and the professional relationship affect the practice of oral hygiene, in particular among dental students. Fashion models, however, are most intensively concerned with body care and oral hygiene. Their attention is directed particularly to means supposed to improve the smile as well as to ensure fresh breath. Dental students and fashion models constitute a selected minority clearly demarcated from students of other disciplines regarding a higher awareness of self-reliant oral hygiene. The comparatively minor rating of oral health in a group of basically well-trained individuals suggests great need of educational work in the general population. PMID- 26678430 TI - A Fluorescent Tile DNA Diagnocode System for In Situ Rapid and Selective Diagnosis of Cytosolic RNA Cancer Markers. AB - Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields. PMID- 26678432 TI - Mental health in cystic fibrosis: turning the tide. PMID- 26678431 TI - Transforming Growth Factor-beta1 Induced Epithelial Mesenchymal Transition is blocked by a chemical antagonist of translation factor eIF4E. AB - The epithelial to mesenchymal transition (EMT) imparts disease-defining properties to epithelial cells in cancer and organ fibrosis. Prior studies identify EMT control points at the level of transcription and translation, and indicate that activation of translation initiation factor 4E (eIF4E) is involved in the mechanisms coordinating these two levels of control. Here we show that 4Ei 1, a specific chemical antagonist of the eIF4E-mRNA cap interaction, potently inhibits transforming growth factor beta 1 (TGF-beta1) mediated EMT in lung epithelial cells. Upon treatment with TGF-beta1, we observed a rapid recruitment of Snail1 mRNA into the actively translated polysome pool accompanied by accumulation of the EMT transcription factor Snail1 in the nucleus. 4Ei-1 blocks ribosome recruitment to the Snail1 transcript thereby preventing accumulation of the Snail1 protein in the nucleus. Our findings establish an obligatory role for upstream translational control of downstream Snail1-mediated transcriptional events in TGF-beta1 induced EMT, and provide proof of concept for efforts to pharmacologically modulate the eIF4E-cap interaction as a means to inhibit pathological EMT in the setting of cancer and organ fibrosis. PMID- 26678433 TI - What defines latent infection with Mycobacterium tuberculosis in patients with autoimmune diseases? PMID- 26678434 TI - Interstitial lung disease: time to rethink the snapshot diagnosis? PMID- 26678435 TI - US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. AB - Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre existing inflammatory lung disease, such as cystic fibrosis (CF). Pulmonary disease (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition. PMID- 26678437 TI - Factors associated with recognition and prioritization for falling, and the effect on fall incidence in community dwelling older adults. AB - BACKGROUND: Recent trials have shown that multifactorial fall interventions vary in effectiveness, possibly due to lack of adherence to the interventions. The aim of this study was to examine what proportion of older adults recognize their falls risk and prioritize for fall-preventive care, and which factors are associated with this prioritization. METHODS: Observational study within the intervention arm of a cluster randomized controlled trial (RCT) on the effect of preventive interventions for geriatric problems in older community-dwellers at risk of functional decline. SETTING: general practices in the Netherlands. Participants were community dwellers (70+) in whom falling was identified as a condition. A comprehensive geriatric assessment (CGA) was performed by a registered community care nurse. Participants were asked which of the identified conditions they recognized and prioritized for in a preventive care plan, and subsequent interventions were started. Multivariable logistic regression was performed to identify which factors were associated with this prioritization. Fall-incidence was measured during one-year follow-up. RESULTS: The RCT included 6668 participants, 3430 were in the intervention arm. Of those, 1209 were at risk of functional decline, of whom 936 underwent CGA. In 380 participants (41 %), falling was identified as a condition; 62 (16 %) recognized this and 37 (10 %) prioritized for it. Factors associated with prioritization for falls-prevention were: recurrent falls in the past year (OR 2.2 [95 % CI 1.1-4.4]), severe fear-of falling (OR 2.7 [1.2-6.0]) and use of a walking aid (2.3 [1.1-5.0]). Sixty participants received a preventive intervention for falling; 29 had prioritized for falling. Incidence of falls was higher in the priority group than the non priority group (67 % vs. 37 % respectively) during first six months of follow-up, but similar between groups after 12 months (40.7 % vs. 44.4 %). CONCLUSIONS: The proportion of community-dwellers at risk of falls that recognizes this risk and prioritizes for preventive care is small. Recurrent falls in the past year, severe fear-of-falling and use of a walking aid were associated with prioritization. Prioritization was associated with a greater fall-risk during first six months, which appeared to level out at one-year follow-up. These results could aid in the identification of community-dwellings likely to benefit from fall-preventive interventions. TRIAL REGISTRATION: NTR2653 , 17 December 2010. PMID- 26678438 TI - Multi-allelic haplotype model based on genetic partition for genomic prediction and variance component estimation using SNP markers. AB - BACKGROUND: The amount of functional genomic information has been growing rapidly but remains largely unused in genomic selection. Genomic prediction and estimation using haplotypes in genome regions with functional elements such as all genes of the genome can be an approach to integrate functional and structural genomic information for genomic selection. Towards this goal, this article develops a new haplotype approach for genomic prediction and estimation. RESULTS: A multi-allelic haplotype model treating each haplotype as an 'allele' was developed for genomic prediction and estimation based on the partition of a multi allelic genotypic value into additive and dominance values. Each additive value is expressed as a function of h - 1 additive effects, where h = number of alleles or haplotypes, and each dominance value is expressed as a function of h(h - 1)/2 dominance effects. For a sample of q individuals, the limit number of effects is 2q - 1 for additive effects and is the number of heterozygous genotypes for dominance effects. Additive values are factorized as a product between the additive model matrix and the h - 1 additive effects, and dominance values are factorized as a product between the dominance model matrix and the h(h - 1)/2 dominance effects. Genomic additive relationship matrix is defined as a function of the haplotype model matrix for additive effects, and genomic dominance relationship matrix is defined as a function of the haplotype model matrix for dominance effects. Based on these results, a mixed model implementation for genomic prediction and variance component estimation that jointly use haplotypes and single markers is established, including two computing strategies for genomic prediction and variance component estimation with identical results. CONCLUSION: The multi-allelic genetic partition fills a theoretical gap in genetic partition by providing general formulations for partitioning multi-allelic genotypic values and provides a haplotype method based on the quantitative genetics model towards the utilization of functional and structural genomic information for genomic prediction and estimation. PMID- 26678439 TI - Maternal and neonatal outcomes in pregnant women with autoimmune diseases in Pavia, Italy. AB - BACKGROUND: The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring. The aim of this study was to determine the impact of autoimmune disease on pregnancy and on neonatal outcome, taking into account the maternal treatment and the transplacental autoantibodies passage. METHODS: We studied 70 infants born to 70 pregnant women with autoimmune disease attended in Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012. Maternal and neonatal characteristics were collected and relevant clinical, laboratory, therapeutics, sonographic and electrocardiographic investigations were recorded and analyzed. RESULTS: We observed a high rate of spontaneous abortions in medical history, 29 %, and 18.6 % of preterm births and 22.9 % of low birth weight (< 2500 g). Transplacental autoantibodies passage wasn't related to maternal or obstetrical complication, but anti-Ro/SSA positive pregnancies correlated with abnormal fetal heart rate (P = 0.01). Pregnant women on therapy showed an higher incidence of maternal (p = 0.002), obstetric (p = 0.007) complications and an increased rate of intrauterine growth restriction (p = 0.01) than the untreated ones. CONCLUSIONS: Autoimmune diseases in pregnancy require to be carefully monitored to ensure the best possible management of mothers, fetuses and newborns due to the high rate of morbidity specially in case of maternal polytherapy and/or anti-Ro/SSA positivity. PMID- 26678440 TI - An evaluation of case completeness for New Zealand Coronial case files held on the Australasian National Coronial Information System (NCIS). AB - Large administrative databases provide powerful opportunities for examining the epidemiology of injury. The National Coronial Information System (NCIS) contains Coronial data from Australia and New Zealand (NZ); however, only closed cases are stored for NZ. This paper examines the completeness of NZ data within the NCIS and its impact upon the validity and utility of this database. A retrospective review of the capture of NZ cases of quad-related fatalities held in the NCIS was undertaken by identifying outstanding Coronial cases held on the NZ Coronial Management System (primary source of NZ Coronial data). NZ data held on the NCIS database were incomplete due to the non-capture of closed cases and the unavailability of open cases. Improvements to the information provided on the NCIS about the completeness of NZ data are needed to improve the validity of NCIS derived findings and the overall utility of the NCIS for research. PMID- 26678441 TI - Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus. AB - OBJECTIVE: Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. METHODS: Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. RESULTS: The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. CONCLUSION: These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. PMID- 26678442 TI - Assessment of premature atherosclerosis in systemic lupus erythematosus patients with and without nephritis. AB - BACKGROUND: Risk of subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE). We correlated carotid intima media thickness (CIMT) and endothelial dysfunction through flow-mediated dilation (FMD) in SLE patients with the SLE Disease Activity Index (SLEDAI). METHODS: This single centre cross-sectional study recruited 100 consenting SLE outpatients (ACR 1997 criteria) out of which 50 had nephritis, with disease duration of >=2 years for SLE and >=6 months for lupus nephritis. We measured baseline laboratory levels, CIMT and FMD (after brachial BP cuff inflation up to 200 mmHg for five minutes), and calculated SLEDAI. RESULTS: Mean age was 29.88 +/- 6.53 years; 95/100 were female. CIMT showed positive correlation (p = 0.037; rho = 0.209), and FMD showed inverse correlation with patient's age (p = 0.011; rho = -0.252). CIMT and FMD were more deranged in patients aged >=25 years (p < 0.05). CIMT was not significantly different between SLE patients with and without nephritis (p > 0.05), whereas SLEDAI and FMD were more deranged in nephritis patients (p < 0.05). In patients without nephritis, FMD showed significant inverse correlation with disease duration (p = 0.043; rho = -0.288) and urine albumin (p = 0.045; rho = -0.285). In nephritis patients, the correlation between age of the patient was significantly positive with CIMT (p = 0.001; rho = 0.441) and significantly inverse with FMD (p = 0.028; rho = -0.312). CONCLUSION: SLE patients with nephritis are at a higher risk to develop arterial stiffening, leading to early end-organ damage. Early aggressive treatment may prevent endothelial dysfunction. FMD using vascular ultrasonography on the brachial artery represents a non invasive, repeatable and useful method for the assessment of endothelial dysfunction. PMID- 26678443 TI - Prevalence of premature ovarian failure in patients with systemic lupus erythematosus. AB - OBJECTIVE: To estimate the prevalence of premature ovarian failure (POF) and its associated factors in patients with systemic lupus erythematosus (SLE). METHODS: Cross-sectional study including consecutive SLE women <60 years of age attending a rheumatology clinic. A face-to-face interview was undertaken to obtain demographic, gynaecological and lupus characteristics. Additional rheumatologic and endocrine data were retrieved from patients' medical records. POF prevalence was estimated in the study sample and in a subgroup of patients aged <40 years at interview. Associations between POF and selected variables were assessed by logistic regression analyses. RESULTS: A total of 961 patients were analysed. Prevalence of POF, secondary amenorrhea of known cause, menopause and hysterectomy were 5.4%, 0.8%, 7.8% and 4.4%, respectively. In 674 (70%) patients who had not been exposed to cyclophosphamide (CYC) the prevalence of POF was 0.6%. Disease activity over time (OR 1.4 (CI 95% 1.0-1.8, p < 0.05)) and CYC treatment (OR 5.9 (CI 95% 1.8-18.8, p < 0.01)) were associated with higher prevalence. Association between POF and endocrine autoimmune diseases was not found. CONCLUSIONS: In the absence of CYC treatment, the prevalence of POF in lupus patients is consistent with that reported in the general population. The existence of autoimmune processes at the ovary seems unlikely in most lupus patients. PMID- 26678444 TI - Physical Therapy Residency and Fellowship Education: Reflections on the Past, Present, and Future. AB - The physical therapy profession continues to respond to the complex and changing landscape of health care to meet the needs of patients and the demands of patient care. Consistent with this evolution is the rapid development and expansion of residency and fellowship postprofessional programs. With the interested number of applicants exceeding the number of residency and fellowship slots available, a "critical period" in the educational process is emerging. The purposes of this perspective article are: (1) to analyze the state of residency and fellowship education within the profession, (2) to identify best practice elements from other health professions that are applicable to physical therapy residency and fellowship education, and (3) to propose a working framework grounded in common domains of competence to be used as a platform for dialogue, consistency, and quality across all residency and fellowship programs. Seven domains of competence are proposed to theoretically ground residency and fellowship programs and facilitate a more consistent approach to curricular development and assessment. Although the recent proliferation of residency and fellowship programs attempts to meet the demand of physical therapists seeking advanced educational opportunities, it is imperative that these programs are consistently delivering high-quality education with a common focus on delivering health care in the context of societal needs. PMID- 26678445 TI - Long-Term Effect of Exercise Therapy and Patient Education on Impairments and Activity Limitations in People With Hip Osteoarthritis: Secondary Outcome Analysis of a Randomized Clinical Trial. AB - BACKGROUND: The effect of exercise on specific impairments and activity limitations in people with hip osteoarthritis (OA) is limited. OBJECTIVE: The study objective was to evaluate the long-term effect of exercise therapy and patient education on range of motion (ROM), muscle strength, physical fitness, walking capacity, and pain during walking in people with hip OA. DESIGN: This was a secondary outcome analysis of a randomized clinical trial. SETTING: The setting was a university hospital. PARTICIPANTS: One hundred nine people with clinically and radiographically evident hip OA were randomly allocated to receive both exercise therapy and patient education (exercise group) or patient education only (control group). INTERVENTION: All participants attended a patient education program consisting of 3 group meetings led by 2 physical therapists. Two other physical therapists were responsible for providing the exercise therapy program, consisting of 2 or 3 weekly sessions of strengthening, functional, and stretching exercises over 12 weeks. Both interventions were conducted at a sports medicine clinic. MEASUREMENTS: Outcome measures included ROM, isokinetic muscle strength, predicted maximal oxygen consumption determined with the Astrand bicycle ergometer test, and distance and pain during the Six-Minute Walk Test (6MWT). Follow-up assessments were conducted 4, 10, and 29 months after enrollment by 5 physical therapists who were unaware of group allocations. RESULTS: No significant group differences were found for ROM, muscle strength, predicted maximal oxygen consumption, or distance during the 6MWT over the follow-up period, but the exercise group had less pain during the 6MWT than the control group at 10 months (mean difference=-8.5 mm; 95% confidence interval=-16.1, -0.9) and 29 months (mean difference=-9.3 mm; 95% confidence interval=-18.1, -0.6). LIMITATIONS: Limitations of the study were reduced statistical power and 53% rate of adherence to the exercise therapy program. CONCLUSIONS: The previously described effect of exercise on self-reported function was not reflected by beneficial results for ROM, muscle strength, physical fitness, and walking capacity, but exercise in addition to patient education resulted in less pain during walking in the long term. PMID- 26678446 TI - Problems, Solutions, and Strategies Reported by Users of Transcutaneous Electrical Nerve Stimulation for Chronic Musculoskeletal Pain: Qualitative Exploration Using Patient Interviews. AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) could offer a non drug form of pain relief, but there is no consensus regarding its effectiveness for chronic musculoskeletal pain or chronic low back pain. A recent review of previous trial methods identified significant problems with low treatment fidelity. There is little information available to inform the development of a pragmatic implementation design for a TENS evaluation. OBJECTIVES: The aim of this study was to explore the experiences of patients who were receiving secondary care in a pain clinic and who had expertise in using TENS to manage chronic musculoskeletal pain. These key informants were selected because they had the potential to generate knowledge that could inform research design and clinical practice. DESIGN: A qualitative method using individual semistructured interviews with open questions was selected for its capacity to generate rich data. METHODS: Semistructured interviews were conducted with 9 patients (6 women, 3 men). Thematic analysis was used as the primary data analysis method, and this analysis was enhanced by a case-level analysis of the context and processes of TENS use of each individual. RESULTS: Data analysis indicated that patients learned to address a range of problems in order to optimize TENS use. Patients may need to personalize the positioning of electrodes and the TENS settings and to readjust them over time. Patients learned to use TENS in a strategic manner, and the outcomes of each strategy varied. CONCLUSIONS: The findings indicated that a pragmatic TENS evaluation may need to incorporate a learning phase to allow patients to optimize this complex pattern of TENS usage, and evaluation may need to be sensitive to the outcomes of strategic use. These findings also have implications for clinical practice. PMID- 26678447 TI - Cost-Effectiveness of Physical Therapy Only and of Usual Care for Various Health Conditions: Systematic Review. AB - BACKGROUND: Given continually rising health care costs, interventions of health care providers should be cost-effective. PURPOSE: This review aimed to summarize current cost-effectiveness of physical therapy. Specific aims were: (1) to analyze cost-effectiveness of physical therapy only compared with usual care only, (2) to analyze cost-effectiveness of physical therapy added to usual care compared with usual care only, and (3) to specify in which health conditions physical therapy only or physical therapy added to usual care was cost-effective. DATA SOURCES: Topic-related systematic reviews were searched in MEDLINE, CINAHL, PEDro, and Cochrane Library and manually. STUDY SELECTION: Studies published between 1998 and 2014 that investigated the cost-effectiveness of interventions carried out by physical therapists were reviewed. The methodological quality was assessed with the Cochrane risk of bias assessment for intervention studies and with the Quality of Health Economic Analyses Scale. DATA EXTRACTION: Effectiveness and cost data for calculating incremental cost-effectiveness ratios (ICERs) and the original authors' conclusions were extracted. DATA SYNTHESIS: The 18 included studies presented low risk of bias and contained 8 comparisons of physical therapy only with usual care only and 11 comparisons of physical therapy added to usual care with usual care only. Based on ICERs, physical therapy only or added to usual care was cost-effective in 9 out of the 19 comparisons and in 10 comparisons according to the original authors' conclusions. CONCLUSION: Physical therapy only or added to usual care implies improved health in almost all studies. The cost-effectiveness of such interventions was demonstrated in half of the studies. This result might have been influenced by the fact that different definitions of the notion of "cost-effectiveness" exist. PMID- 26678448 TI - Raising the Priority of Lifestyle-Related Noncommunicable Diseases in Physical Therapy Curricula. AB - Given their enormous socioeconomic burdens, lifestyle-related noncommunicable diseases (heart disease, cancer, chronic lung disease, hypertension, stroke, type 2 diabetes mellitus, and obesity) have become priorities for the World Health Organization and health service delivery systems. Health care systems have been criticized for relative inattention to the gap between knowledge and practice, as it relates to preventing and managing noncommunicable diseases. Physical therapy is a profession that can contribute effectively to patients'/clients' lifestyle behavior changes at the upstream end of prevention and management. Efforts by entry-to-practice physical therapist education programs to align curricula with epidemiological trends toward best health care practices are varied. One explanation may be the lack of a frame of reference for reducing the knowledge translation gap. The purpose of this article is to provide a current perspective on epidemiological indicators and societal priorities to inform physical therapy curriculum content. Such content needs to include health examination/evaluation tools and health behavior change interventions that are consistent with contemporary values, directions, and practices of physical therapy. These considerations provide a frame of reference for curriculum change. Based on 5 years of experience and dialogue among curriculum stakeholders, an example of how epidemiologically informed and evidence-based best health care practices may be systematically integrated into physical therapy curricula to maximize patient/client health and conventional physical therapy outcomes is provided. This novel approach can serve as an example to other entry-to-practice physical therapist education programs of how to align their curricula with societal health priorities, specifically, noncommunicable diseases. The intentions are to stimulate dialogue about effectively integrating health-based competencies into entry-level education and advancing best practice, as opposed to simply evidence based practice, across professions and health services and to establish accreditable, health promotion practice standards for physical therapy. PMID- 26678450 TI - The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor. AB - Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR duringLeishmania amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 MUM) increasedL. amazonensisinfectivity in an IFN1-alpha receptor (IFNAR)-dependent manner. In Western blot assays, we showed thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-beta expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude thatL. amazonensisactivation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-beta expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response inLeishmania amazonensismacrophage infection: the role of X-box binding protein 1 transcription factor. PMID- 26678449 TI - Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant mediated aspermatogenesis and barrier disruption. AB - Earlier studies have shown that rats treated with an acute dose of 1-(2,4 dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to support round spermatids to enter spermiogenesis.-Li, N., Mruk, D. D., Mok, K.-W., Li, M. W. M., Wong, C. K. C., Lee, W. M., Han, D., Silvestrini, B., Cheng, C. Y. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption. PMID- 26678451 TI - Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d. AB - Complement regulation leads to the generation of complement split products (CSPs) such as complement component (C)4d, a marker for disease activity in autoimmune syndromes or antibody-mediated allograft rejection. However, the physiologic role of C4d has been unknown. By screening murine thymoma BW5147 cells expressing a cDNA library generated from human monocyte-derived dendritic cells with recombinant human C4d, we identified Ig-like transcript (ILT)4 and ILT5v2 as cellular receptors for C4d. Both receptors, expressed on monocytes, macrophages, and dendritic cells, also interacted with the CSPs C3d, C4b, C3b, and iC3b. However, C4d did not bind to classic complement receptors (CRs). Interaction between cell surface-resident ILT4 and soluble monomeric C4d resulted in endocytosis of C4d. Surprisingly, binding of soluble ILT4 to C4d covalently immobilized to a cellular surface following classic complement activation could not be detected. Remarkably, C4d immobilized to a solid phaseviaits intrinsic thioester conferred a dose-dependent inhibition of TNF-alpha and IL-6 secretion in monocytes activatedviaFc-cross-linking of up to 50% as compared to baseline. Similarly, C4d conferred an attenuation of intracellular Ca(2+)flux in monocytes activatedviaFc-cross-linking. In conclusion, ILT4 represents a scavenger-type endocytotic CR for soluble monomeric C4d, whereas attenuation of monocyte activation by physiologically oriented C4d on a surface appears to be dependent on a yet to be identified C4d receptor.-Hofer, J., Forster, F., Isenman, D. E., Wahrmann, M., Leitner, J., Holzl, M. A., Kovarik, J. K., Stockinger, H., Bohmig, G. A., Steinberger, P., Zlabinger, G. J. Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d. PMID- 26678452 TI - Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells. AB - While a variety of short interfering RNA (siRNA) delivery compounds have been developed, a deep understanding of the key parameters that determine the quality of siRNA delivery are not known with certainty. Therefore, an understanding of the factors required for the efficient, selective, and safe delivery of siRNA is a great challenge for successful siRNA delivery. Herein, we report on the development of two pH-sensitive cationic lipids and their use in examining the impact of the acid dissociation constant (pKa) value, lipase sensitivity and the size of lipid nanoparticles on the biodistribution, and efficiency and cell specificity of gene silencing in the liver. An increase in the pKa value resulted in a significant change in the intrahepatic localization of siRNA and gene silencing efficiency in hepatocytes and liver sinusoidal endothelial cells (LSECs). The sensitivity of the pH-sensitive cationic lipid to lipases was a major factor in achieving hepatocyte-specific gene silencing. Increasing the particle size can improve the LSEC specificity of gene silencing. As a consequence, we succeeded in developing both a highly efficient, hepatocyte specific formulation, and the most efficacious LSEC-targeted formulation reported to date. These findings will facilitate the development of more sophisticated siRNA delivery systems. PMID- 26678454 TI - Pediatric En Bloc Kidney Transplants: Clinical and Immediate Postoperative US Factors Associated with Vascular Thrombosis. AB - Purpose To evaluate clinical and immediate postoperative ultrasonographic (US) risk factors associated with vascular thrombosis of pediatric en bloc kidney grafts. Materials and Methods This institutional review board-approved HIPAA compliant retrospective study consisted of 195 recipients of pediatric en bloc kidney grafts throughout a 10-year period. The average recipient and donor age was 45 years (range, 7-74 years) and 9 months (range, 0-84 months), respectively. Clinical factors and immediate postoperative US findings were assessed. Categorical variables were evaluated by using the Fisher exact test and linear models with generalized estimating equations. Results Seventeen patients (23 kidneys) experienced thrombotic events. In six patients (eight kidneys), thrombosis occurred intraoperatively. The remaining 11 patients (15 kidneys) received a diagnosis of thrombosis on postoperative days 1-13. Recipients more than 40 years old had a higher incidence of arterial thrombosis than did younger recipients (eight of 62 vs three of 133, respectively; P < .01). Recipients were more likely to develop thrombosis with donor weight less than 5 kg (10 of 52 vs seven of 140 with donor weight of >= 5 kg; P < .01), with intraoperative perfusional concern (10 of 21 vs seven of 174 without; P < .01), or with right sided allograft placement (10 of 64 vs seven of 131 left sided; P = .03). At US of the 15 postoperative thrombotic events, the incidence of thrombosis was greater when donor arterial velocity was less than 100 cm/sec (seven of 56 vs four of 126 with velocity >= 100 cm/sec; P = .04). An intrarenal arterial resistive index of less than 0.6 was associated with higher incidence of arterial thrombosis (nine of 123 vs zero of 217, respectively; P = .01). A resistive index greater than 0.8 was associated with a higher incidence of venous thrombosis (four of 13 vs one of 217, respectively; P = .04). Conclusion Clinical factors and immediate US findings can help stratify patients receiving pediatric en bloc kidneys into risk categories for vascular thrombosis that, if proven in prospective studies, could affect immediate postoperative treatment. ((c)) RSNA, 2015. PMID- 26678453 TI - Multimodality Imaging of Ethiodized Oil-loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors. AB - Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70-150-MUm radiopaque microspheres in saline (radiopaque microsphere group), 70-150-MUm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70-150-MUm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement. For the group with nonradiopaque microspheres and contrast material, retained tumoral contrast remained qualitatively visible with all modalities except for micro-CT, which demonstrated soluble contrast material washout over time. Conclusion Radiopaque microspheres were visible with all imaging modalities and helped increase conspicuity of the tumor as well as its feeding arteries after TAE in a rabbit VX2 liver tumor model. ((c)) RSNA, 2015. PMID- 26678455 TI - Comparison of Intravoxel Incoherent Motion Parameters across MR Imagers and Field Strengths: Evaluation in Upper Abdominal Organs. AB - Purpose To determine the reproducibility of intravoxel incoherent motion (IVIM) parameters measured in upper abdominal organs with magnetic resonance (MR) imagers from different vendors and with different field strengths. Materials and Methods This prospective study was approved by the independent ethics committees of Kanton Bern and Kanton Zurich, and signed informed consent was obtained from all participants. Abdominal diffusion-weighted images in 10 healthy men (mean age, 37 years +/- 8 [standard deviation]) were acquired by using 1.5- and 3.0-T MR imagers from three different vendors. Two readers independently delineated regions of interest that were used to measure IVIM parameters (diffusion coefficient [Dt], perfusion fraction [Fp], and pseudodiffusion coefficient [Dp]) in the left and right lobes of the liver, and in the pancreas, spleen, renal cortex, and renal medulla. Measurement reproducibility between readers was assessed with intraclass correlation coefficients (ICCs). Variability across MR imagers was analyzed by using between- and within-subject coefficients of variation (CVs) and analysis of variance (ANOVA). Results Between-reader reproducibility was high for Dt (ICC, 94.6%), intermediate for Fp (ICC, 81.7%), and low for Dp (ICC, 69.5%). Between- and within-subject CVs of Dt were relatively high (>20%) in the left lobe of the liver and relatively low (<10%) in the renal cortex and renal medulla. CVs generally exceeded 15% for Fp values and 20% for Dp. ANOVA indicated significant differences (P < .05) between MR imagers. Conclusion IVIM parameters in the upper abdomen may differ substantially across MR imagers. ((c)) RSNA, 2015 Online supplemental material is available for this article. PMID- 26678456 TI - Wireless fluorescence capsule for endoscopy using single photon-based detection. AB - Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 MUM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue. PMID- 26678457 TI - Synthesis, characterization and photoinduced charge separation of carbon nanohorn oligothienylenevinylene hybrids. AB - The covalent coupling between oligo(thienylenevinylenes) (nTVs) and carbon nanohorns (CNHs) has been investigated. The resulting nanohybrids have been characterized by a combination of several techniques, including thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM) and Raman spectroscopy. The photophysical properties of the new hybrids were investigated by steady-state and time-resolved spectroscopic techniques. A transient signal characterized by two kinetic regimes, one short decay within 0.5 MUs corresponding to around 80% of the total signal and another much longer-lived decay of 10 MUs, has been detected. The transient absorption spectra are characterized by a continuous absorption that increases in intensity towards shorter wavelengths, with a maximum at 430 nm. These transient signals have been assigned to the charge separated state delocalized on CNHs based on the quenching behavior and by comparison with the photophysical properties of nTV in the absence and presence of quenchers. The photophysical behavior of covalent nTV-CNH conjugates with microsecond transients due to electrons and holes on CNHs contrasts with the absence of any transient for analogous nTV-C60 conjugates, for which charge separation was not observed at timescales longer than nanoseconds. The photochemical behavior of CNHs is believed to derive from the amphoteric (electron donor and acceptor) properties of CNHs and from the larger number of carbon atoms (efficient delocalization) in CNHs compared with C60. PMID- 26678458 TI - Target-Controlled Infusions: Surfing USA Redux. PMID- 26678459 TI - Closed-Loop Propofol Administration: Routine Care or a Research Tool? What Impact in the Future? PMID- 26678460 TI - No Matter the Perspective, Anesthesia Handoffs Are Problematic. PMID- 26678461 TI - Legal Research Databases to Study Rare Perioperative Outcomes in Patients with Obstructive Sleep Apnea. PMID- 26678462 TI - Clinically Important Difference in Quality of Recovery Scores. PMID- 26678463 TI - Deliberate Hypotension for Hip Arthroplasty: Still More Questions Than Answers. PMID- 26678464 TI - Virtuous Coding and the Coming Revolution in Payment for Professional Services. PMID- 26678465 TI - Intraoperative Use of Vascular Ultrasound to Localize Thrombus in Left Ventricular Assist Device Exchange. PMID- 26678466 TI - Papillary Fibroelastoma of the Pulmonary Valve: The Value of Three-Dimensional Transesophageal Echocardiography. PMID- 26678467 TI - Failed Percutaneous Transcatheter Tricuspid Valve-in-Valve Replacement Caused by Retained Valve Holder. PMID- 26678468 TI - Aortic Regurgitation: Echocardiographic Diagnosis. PMID- 26678469 TI - The Contribution of Pin End-Cup Interactions to Clot Strength Assessed with Thrombelastography. AB - Viscoelastic methods have been developed to assess the contribution of plasma proteins and platelets to coagulation in vitro to guide clinical transfusion therapy. One of the cardinal precepts of determining clot strength is making sure that the viscoelastic technique includes complete exposure of the plastic pin in the testing chamber with the fluid analyzed so as to assure maximal interaction of the cup wall with the pin surface. However, the various contributions of the pin surface area to final clot strength have not been investigated. That is, it is not clear what is more important in the in vitro determination of clot strength, the surface area shared between the cup and pin filled with fluid or the final viscoelastic resistance of the gel matrix formed. Thus, the purpose of this investigation was to determine the clot strength when only the tip of the pin was engaged with plasma thrombus and to compare these values with clot strength values obtained when the pin was completely in plasma. After determining the minimal amount of plasma required to cover a pin tip in a thrombelastographic system (30 MUL), clot strength (elastic modulus, G) was determined in plasma samples of 30 or 360 MUL final volume (n = 12 per condition) after tissue factor activation. The G value with 30 MUL volume was 1057 +/- 601 dynes/cm (mean +/- SD; 95% confidence interval, 675-1439 dynes/cm), which was (P = 0.0015) smaller than the G value associated with 360-MUL sample volumes, that was 1712 +/- 48 dynes/cm (confidence interval, 1681-1742 dynes/cm). In conclusion, these data demonstrate that clot strength is not determined by a simple ratio of surface area of pin and cup to volume of sample, but rather strength is importantly influenced by the viscoelastic resistance of the fluid assessed. PMID- 26678470 TI - Efficacy Outcome Measures for Procedural Sedation Clinical Trials in Adults: An ACTTION Systematic Review. AB - Successful procedural sedation represents a spectrum of patient- and clinician related goals. The absence of a gold-standard measure of the efficacy of procedural sedation has led to a variety of outcomes being used in clinical trials, with the consequent lack of consistency among measures, making comparisons among trials and meta-analyses challenging. We evaluated which existing measures have undergone psychometric analysis in a procedural sedation setting and whether the validity of any of these measures support their use across the range of procedures for which sedation is indicated. Numerous measures were found to have been used in clinical research on procedural sedation across a wide range of procedures. However, reliability and validity have been evaluated for only a limited number of sedation scales, observer-rated pain/discomfort scales, and satisfaction measures in only a few categories of procedures. Typically, studies only examined 1 or 2 aspects of scale validity. The results are likely unique to the specific clinical settings they were tested in. Certain scales, for example, those requiring motor stimulation, are unsuitable to evaluate sedation for procedures where movement is prohibited (e.g., magnetic resonance imaging scans). Further work is required to evaluate existing measures for procedures for which they were not developed. Depending on the outcomes of these efforts, it might ultimately be necessary to consider measures of sedation efficacy to be procedure specific. PMID- 26678471 TI - Methylene Blue: Magic Bullet for Vasoplegia? AB - Methylene blue (MB) has received much attention in the perioperative and critical care literature because of its ability to antagonize the profound vasodilation seen in distributive (also referred to as vasodilatory or vasoplegic) shock states. This review will discuss the pharmacologic properties of MB and review the critical care, liver transplantation, and cardiac anesthesia literature with respect to the efficacy and safety of MB for the treatment of shock. Although improved blood pressure has consistently been demonstrated with the use of MB in small trials and case reports, better oxygen delivery or decreased mortality with MB use has not been demonstrated. Large randomized controlled trials are still necessary to identify the role of MB in hemodynamic resuscitation of the critically ill. PMID- 26678472 TI - Quantifying the Diversity and Similarity of Surgical Procedures Among Hospitals and Anesthesia Providers. AB - In this Statistical Grand Rounds, we review methods for the analysis of the diversity of procedures among hospitals, the activities among anesthesia providers, etc. We apply multiple methods and consider their relative reliability and usefulness for perioperative applications, including calculations of SEs. We also review methods for comparing the similarity of procedures among hospitals, activities among anesthesia providers, etc. We again apply multiple methods and consider their relative reliability and usefulness for perioperative applications. The applications include strategic analyses (e.g., hospital marketing) and human resource analytics (e.g., comparisons among providers). Measures of diversity of procedures and activities (e.g., Herfindahl and Gini Simpson index) are used for quantification of each facility (hospital) or anesthesia provider, one at a time. Diversity can be thought of as a summary measure. Thus, if the diversity of procedures for 48 hospitals is studied, the diversity (and its SE) is being calculated for each hospital. Likewise, the effective numbers of common procedures at each hospital can be calculated (e.g., by using the exponential of the Shannon index). Measures of similarity are pairwise assessments. Thus, if quantifying the similarity of procedures among cases with a break or handoff versus cases without a break or handoff, a similarity index represents a correlation coefficient. There are several different measures of similarity, and we compare their features and applicability for perioperative data. We rely extensively on sensitivity analyses to interpret observed values of the similarity index. PMID- 26678473 TI - Distribution of Injectate and Sensory-Motor Blockade After Adductor Canal Block. AB - BACKGROUND: The analgesic efficacy reported for the adductor canal block may be related to the spread of local anesthetic outside the adductor canal. METHODS: Fifteen patients undergoing knee surgery received ultrasound-guided injections of local anesthetic at the level of the adductor hiatus. Sensory-motor block and spread of contrast solution were assessed. RESULTS: Sensation was rated as "markedly diminished" or "absent" in the saphenous nerve distribution and "slightly diminished" in the sciatic nerve territory without motor deficits. Contrast solution was found in the popliteal fossa. CONCLUSIONS: The spread of injectate to the popliteal fossa may contribute to the analgesic efficacy of adductor canal block. PMID- 26678474 TI - Target-Controlled Infusions Could Improve the Safety and Efficacy of Emergency Department Propofol Sedation. PMID- 26678475 TI - Optimal Surgical Conditions in Laparoscopic Surgery: Just Relax and Lower the Pressure. PMID- 26678476 TI - Deep Neuromuscular Blockade for Laparoscopy: A Different View. PMID- 26678477 TI - In Response. PMID- 26678478 TI - Laparoscopic Surgery and Muscle Relaxants: Is Deep Block Really Not Helpful? PMID- 26678479 TI - Lawyers Choose Specific Experts for Many Different Reasons. PMID- 26678480 TI - In Response. PMID- 26678481 TI - Disruption Interrupted. PMID- 26678482 TI - The Pediatric Perioperative Surgical Home. PMID- 26678483 TI - IL-1beta induces hypomyelination in the periventricular white matter through inhibition of oligodendrocyte progenitor cell maturation via FYN/MEK/ERK signaling pathway in septic neonatal rats. AB - Neuroinflammation elicited by microglia plays a key role in periventricular white matter (PWM) damage (PWMD) induced by infectious exposure. This study aimed to determine if microglia-derived interleukin-1beta (IL-1beta) would induce hypomyelination through suppression of maturation of oligodendrocyte progenitor cells (OPCs) in the developing PWM. Sprague-Dawley rats (1-day old) were injected with lipopolysaccharide (LPS) (1 mg/kg) intraperitoneally, following which upregulated expression of IL-1beta and IL-1 receptor 1 (IL-1R1 ) was observed. This was coupled with enhanced apoptosis and suppressed proliferation of OPCs in the PWM. The number of PDGFR-alpha and NG2-positive OPCs was significantly decreased in the PWM at 24 h and 3 days after injection of LPS, whereas it was increased at 14 days and 28 days. The protein expression of Olig1, Olig2, and Nkx2.2 was significantly reduced, and mRNA expression of Tcf4 and Axin2 was upregulated in the developing PWM after LPS injection. The expression of myelin basic protein (MBP) and 2',3'-cyclic-nucleotide 3"-phosphodiesterase (CNPase) was downregulated in the PWM at 14 days and 28 days after LPS injection; this was linked to reduction of the proportion of myelinated axons and thinner myelin sheath as revealed by electron microscopy. Primary cultured OPCs treated with IL 1beta showed the failure of maturation and proliferation. Furthermore, FYN/MEK/ERK signaling pathway was involved in suppression of maturation of primary OPCs induced by IL-1beta administration. Our results suggest that following LPS injection, microglia are activated and produce IL-1beta in the PWM in the neonatal rats. Excess IL-1beta inhibits the maturation of OPCs via suppression of FYN/MEK/ERK phosphorylation thereby leading to axonal hypomyelination. PMID- 26678485 TI - Correction: An Automated, Adaptive Framework for Optimizing Preprocessing Pipelines in Task-Based Functional MRI. PMID- 26678484 TI - In vitro biofilm production of Candida bloodstream isolates: any association with clinical characteristics? AB - Candida spp. are a leading cause of bloodstream infection (BSI) and are associated with high mortality rates. Biofilm production is a virulence factor of Candida spp., and has been linked with poor clinical outcome. The aim of our study was to assess biofilm production of Candida bloodstream isolates at our institute, and to determine whether in vitro biofilm production is associated with any clinical characteristics of infection. During the four-year study period, 93 cases of Candida BSI were analysed. The most frequently isolated species was C. albicans (66.7 %), followed by C. glabrata (9.7 %), C. parapsilosis (9.7 %), C. tropicalis (9.7 %) and C. krusei (4.3 %). Biofilm production was more prevalent among non-albicans Candida spp. (77.4 %) than C. albicans (30.6 %) (P = 0.02). Abdominal surgery was identified as a risk factor of BSI caused by biofilm producing non-albicans Candida isolates. No risk factors predisposing to bloodstream infection caused by a biofilm producing C. albicans isolate were identified. Biofilm production was not verified as a risk factor of mortality. PMID- 26678486 TI - Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center. AB - Familial intrahepatic cholestases (FICs) are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC) or a benign recurrent intrahepatic cholestasis (BRIC). For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5'UTR- exon 18) in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission. PMID- 26678487 TI - Formal Comment on Schorr GS, Falcone EA, Moretti DJ, Andrews RD (2014) First Long Term Behavioral Records from Cuvier's Beaked Whales (Ziphius cavirostris) Reveal Record-Breaking Dives. PLoS ONE 9(3): e92633. doi:10.1371/journal.pone.0092633. PMID- 26678488 TI - Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population. AB - BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients. PATIENTS AND METHODS: Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner. RESULTS: Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4 ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing. CONCLUSIONS: The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy. PMID- 26678489 TI - Factors Affecting Hospital Mortality in Patients with Esophagogastric Anastomotic Leak: A Retrospective Study. AB - OBJECTIVE: We aimed to clarify the association between anastomotic leak and leak associated mortality to assist decision-making and reduce hospital mortality. BACKGROUND: Anastomotic leak is a common complication after esophagectomy, but the nature of its relationship to leak-associated mortality has not been established. METHODS: A retrospective review of all esophagogastric anastomotic leaks that had occurred between 2008 and 2012 at our institution (n = 246) was performed. Risk factors for leak-associated mortality were determined using a multivariate logistic regression analysis. RESULTS: Of the 246 patients with anastomotic leaks, 14 (5.7 %) died. Leak-associated mortality rates were similar regardless of anastomosis location (cervical vs. thoracic anastomosis), surgical approaches (retrosternal vs. prevertebral reconstruction route) and anastomotic techniques (hand-sewn vs. mechanical anastomosis). When a leak occurred, risk factors for leak-associated mortality as determined by multivariate logistic analysis included patient age >60 years (P = 0.029) and the occurrence of the leak within 1 week of surgery (P = 0.039). When disease worsened after treatment, leak-associated mortality was more frequent in patients requiring reintubation (25.6 vs. 1.4 %, P < 0.001). Fatal bleeding and sepsis were the most common causes of leak-associated mortality. CONCLUSION: In patients with anastomotic leaks, patient age >60 years and the occurrence of the leak within 1 week of surgery were risk factors for leak-associated mortality. Increased efforts to reduce the incidence of early anastomotic leaks within 1 week after surgery and prevent the need for reintubation are important for improving patient prognosis. PMID- 26678490 TI - Impact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgery. AB - BACKGROUND: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence. METHODS: Fifty-five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high-risk endocrine neck surgery. CIONM was performed using the commercially available NIM-Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded. RESULTS: APS malfunction occurred on three sides (3%). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34%) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66%) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42%) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients. CONCLUSIONS: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high-risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time. PMID- 26678491 TI - Chronic widespread bodily pain is increased among individuals with history of fracture: findings from UK Biobank. AB - SUMMARY: In this cross-sectional analysis of the UK Biobank cohort, a history of fracture was associated with increased risk of current widespread chronic pain. PURPOSE/INTRODUCTION: We aimed to test the hypothesis that a history of fracture is associated with reporting chronic widespread bodily pain (CWBP), using baseline data from the UK Biobank cohort, comprising 502,656 people aged 40-69 years. METHODS: The case definition of current chronic widespread bodily pain was based on a response of 'yes' to the question 'do you have pain all over the body?' and 'yes' to 'and have you experienced pain all over the body for more than 3 months?' Multivariable Poisson regression with robust standard errors was used to test the relationship between fracture (occurring within 5 years prior to the baseline interview, and recorded by self-report) at the spine, hip, upper limb or lower limb and CWBP, adjusting for confounders. RESULTS: Of 501,733 participants (mean age 56.5 years), 7130 individuals reported CWBP and 23,177 had a history of fracture affecting the upper limb, lower limb, spine and/or hip. Individuals with prior fracture were significantly more likely to report CWBP than those without. After adjustment for potential risk factors (age, gender, demographic, lifestyle and socioeconomic, and psychological), risk ratios were attenuated but remained statistically significant with a more than doubling of risk for CWBP with spine fractures in men (risk ratio (RR) 2.67, 95% confidence interval (CI) 1.66-4.31; p < 0.001) and women (RR 2.13, 95% CI 1.35-3.37, p = 0.001) and with hip fractures in women (RR 2.19, 95% CI 1.33-3.59; p = 0.002). CONCLUSIONS: In this cross-sectional analysis, previous fracture is associated with an increased likelihood of chronic widespread bodily pain, particularly with hip fractures in women, and spine fractures in both sexes. If replicated, these findings may help inform the identification of those most at risk of chronic widespread pain post-fracture, allowing preventative measures to be targeted. PMID- 26678493 TI - Fertility in young patients following treatment for Hodgkin's lymphoma: a single center survey. AB - PURPOSE: The purpose of this study was to determine the fertility rates following treatment by means of the BEACOPP regimen (regular and escalated) (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) as compared to the ABVD regimen (doxorubicin, vinblastine, dacarbazine, bleomycin) in Hodgkin lymphoma patients under the age of 40 at the time of treatment. METHODS: A questionnaire was sent to 180 Hodgkin lymphoma (HL) patients. The questionnaire was composed of questions concerning reproduction and also menopausal and aging symptoms in females and males. The analyses were made using data collected from 123 patients (76 females and 47 males) who returned the questionnaire. All of the patients were treated between 1999 and 2012. RESULTS: In comparing the ABVD and BEACOPP groups of female patients, the frequency of the therapy-induced amenorrhea and the restored menses following treatment were found to be significantly different statistically (p = 0.002 and p = 0.012, respectively). The secondary amenorrhea statistically appeared more often in the BEACOPP group (p = 0.003) while the cases of achieving pregnancy and having children after chemotherapy were not significantly different (p = 0.630, p = 0.070, respectively). In comparing the ABVD and BEACOPP treatments in male patients, the only significant difference was in the number of artificially inseminated or in vitro pregnancies achieved in the BEACOPP and escalated BEACOPP group, p = 0.008 and p = 0.002, respectively. In total, 45.2% of patients in the ABVD female group, 34.6% in the BEACOPP female group, 52.6% in the ABVD male group, and 33.3% in the male BEACOPP group, respectively, of patients attempting conception post-therapy, had children after chemotherapy. CONCLUSIONS: Based on these high rates of childbirth following BEACOPP chemotherapy, we have concluded that intensified chemotherapy is not a definite predictor of reduced fertility in young HL patients. PMID- 26678492 TI - Impact of sperm DNA chromatin in the clinic. AB - The paternal contribution to fertilization and embryogenesis is frequently overlooked as the spermatozoon is often considered to be a silent vessel whose only function is to safely deliver the paternal genome to the maternal oocyte. In this article, we hope to demonstrate that this perception is far from the truth. Typically, infertile men have been unable to conceive naturally (or through regular IVF), and therefore, a perturbation of the genetic integrity of sperm heads in infertile males has been under-considered. The advent of intracytoplasmic sperm injection (ICSI) however has led to very successful treatment of male factor infertility and subsequent widespread use in IVF clinics worldwide. Until recently, little concern has been raised about the genetic quality of sperm in ICSI patients or the impact genetic aberrations could have on fertility and embryogenesis. This review highlights the importance of chromatin packaging in the sperm nucleus as essential for the establishment and maintenance of a viable pregnancy. PMID- 26678494 TI - Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats. AB - General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments. PMID- 26678496 TI - Medical Stents: State of the Art and Future Directions. PMID- 26678497 TI - Complementarity and Area-Efficiency in the Prioritization of the Global Protected Area Network. AB - Complementarity and cost-efficiency are widely used principles for protected area network design. Despite the wide use and robust theoretical underpinnings, their effects on the performance and patterns of priority areas are rarely studied in detail. Here we compare two approaches for identifying the management priority areas inside the global protected area network: 1) a scoring-based approach, used in recently published analysis and 2) a spatial prioritization method, which accounts for complementarity and area-efficiency. Using the same IUCN species distribution data the complementarity method found an equal-area set of priority areas with double the mean species ranges covered compared to the scoring-based approach. The complementarity set also had 72% more species with full ranges covered, and lacked any coverage only for half of the species compared to the scoring approach. Protected areas in our complementarity-based solution were on average smaller and geographically more scattered. The large difference between the two solutions highlights the need for critical thinking about the selected prioritization method. According to our analysis, accounting for complementarity and area-efficiency can lead to considerable improvements when setting management priorities for the global protected area network. PMID- 26678495 TI - Role of Nurr1 in the Generation and Differentiation of Dopaminergic Neurons from Stem Cells. AB - NURR1 is an essential transcription factor for the differentiation, maturation, and maintenance of midbrain dopaminergic neurons (DA neurons) as it has been demonstrated using knock-out mice. DA neurons of the substantia nigra pars compacta degenerate in Parkinson's disease (PD) and mutations in the Nurr1 gene have been associated with this human disease. Thus, the study of NURR1 actions in vivo is fundamental to understand the mechanisms of neuron generation and degeneration in the dopaminergic system. Here, we present and discuss findings indicating that NURR1 is a valuable molecular tool for the in vitro generation of DA neurons which could be used for modeling and studying PD in cell culture and in transplantation approaches. Transduction of Nurr1 alone or in combination with other transcription factors such as Foxa2, Ngn2, Ascl1, and Pitx3, induces the generation of DA neurons, which upon transplantation have the capacity to survive and restore motor behavior in animal models of PD. We show that the survival of transplanted neurons is increased when the Nurr1-transduced olfactory bulb stem cells are treated with GDNF. The use of these and other factors with the induced pluripotent stem cell (iPSC)-based technology or the direct reprogramming of astrocytes or fibroblasts into human DA neurons has produced encouraging results for the study of the cellular and molecular mechanisms of neurodegeneration in PD and for the search of new treatments for this disease. PMID- 26678498 TI - Outcome of Multifetal Pregnancy Reduction in Women with a Dichorionic Triamniotic Triplet Pregnancy to a Singleton Pregnancy: A Retrospective Nationwide Cohort Study. AB - OBJECTIVE: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. METHODS: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. RESULTS: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery <24 weeks occurred in 9 (19.6%) women with a reduced triplet pregnancy and 4 (9.5%) with an ongoing triplet pregnancy (p = 0.19). Perinatal survival rates between the reduced group and the ongoing triplet group were not significantly different. CONCLUSION: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates. PMID- 26678499 TI - Organ-specific transcriptome response of the small brown planthopper toward rice stripe virus. AB - Rice stripe virus (RSV) causes rice stripe disease and is transmitted by the small brown planthopper (Laodelphax striatellus, SBPH) in a persistent, circulative, and propagative manner. The alimentary canal and salivary gland of SBPH play important roles in viral replication and transmission. However, little is known about the underlying molecular functions of these two organs in the interaction between RSV and SBPH. In this study, organ-specific transcriptomes of the alimentary canal and salivary gland were analyzed in viruliferous and naive SBPH. The number of differentially expressed unigenes in the alimentary canal was considerably greater than that in the salivary gland after RSV infection, and only 23 unigenes were co-regulated in the two organs. In the alimentary canal, genes involved in lysosome, digestion and detoxification were activated upon RSV infection, whereas the genes related to DNA replication and repair were suppressed. RSV activated RNA transport and repressed the MAPK, mTOR, Wnt, and TGF-beta signaling pathways in the salivary gland. The overall immune reaction toward RSV was much stronger in the salivary gland than in the alimentary canal. RSV activated the pattern recognition molecules and Toll pathway in the salivary gland but inhibited these two reactions in the alimentary canal. The responses from reactive oxygen and the immune-responsive effectors were stronger in the salivary gland than in the alimentary canal after RSV infection. These findings provide clues on the roles of the two organs in confronting RSV infection and aid in the understanding of the interaction between RSV and SBPHs. PMID- 26678500 TI - Pulmonary ultrasound image: The defining point between pneumothorax and pleural effusion. PMID- 26678501 TI - Straightforward synthesis of tetraalkynylpyrazines and their photophysical properties. AB - Tetrafold Sonogashira reactions of tetrachloropyrazine were investigated to provide a one-step synthesis of various tetraalkynylpyrazines. The reaction conditions were thoroughly optimized using modern catalysts and ligands, and products were generally isolated in good to excellent yields. Furthermore, photophysical and electrochemical properties of selected compounds were studied and compared with those of previously reported tetraalkynylpyridines and benzenes. As a matter of fact, tetraalkynylpyrazines proved to show very promising fluorescence properties due to very high quantum yields reaching up to 0.85. PMID- 26678502 TI - Impact of changes in television viewing time and physical activity on longevity: a prospective cohort study. AB - BACKGROUND: Television viewing is a highly prevalent sedentary behavior among older adults, yet the mortality risks associated with hours of daily viewing over many years and whether increasing or decreasing viewing time affects mortality is unclear. This study examined: 1) the long-term association between mortality and daily viewing time; 2) the influence of reducing and increasing in television viewing time on longevity and 3) combined effects of television viewing and moderate-to-vigorous physical activity (MVPA) on longevity. METHODS: Participants included 165,087 adults in the NIH-AARP Diet and Health (aged 50-71 yrs) who completed questionnaires at two-time-points (Time 1: 1994-1996, and Time 2: 2004 2006) and were followed until death or December 31, 2011. Multivariable-adjusted Cox proportional hazards regression was used to estimate Hazard Ratios and 95% confidence intervals (CI) with self-reported television viewing and MVPA and all cause mortality. RESULTS: Over 6.6 years of follow-up, there were 20,104 deaths. Compared to adults who watched < 3 h/day of television at both time points, mortality risk was 28% greater (CI:1.21,1.34) those who watched 5+ h/day at both time-points. Decreasing television viewing from 5 + h/day to 3-4 h/d was associated with a 15% reduction in mortality risk (CI:0.80, 0.91) and decreasing to <3 h/day resulted in an 12% lower risk (CI:0.79, 0.97). Conversely, adults who increased their viewing time to 3-4 h/day had an 17% greater mortality risk (CI:1.10, 1.24) and those who increased to 5+ h/day had a 45% greater risk (CI:1.32, 1.58), compared to those who consistently watched <3 h/day. The lowest mortality risk was observed in those who were consistently active and watched < 3 h/day of television. CONCLUSIONS: We confirm that prolonged television viewing time was associated with greater mortality in older adults and demonstrate for the first time that individuals who reduced the amount of time they spent watching television had lower mortality. Our findings provide new evidence to support behavioral interventions that seek to reduce sedentary television viewing in favor of more physically active pursuits, preferably MVPA. Given the high prevalence of physical inactivity and prolonged television viewing in older adults, favorable changes in these two modifiable behaviors could have substantial public health impact. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00340015. PMID- 26678503 TI - Cloning of two LIMCH1 isoforms: characterization of their distribution in rat brain and their agmatinase activity. AB - Agmatine, a precursor for polyamine biosynthesis, is also associated with neurotransmitter, anticonvulsant, antineurotoxic and antidepressant actions in the brain. This molecule results from the decarboxylation of L-arginine by arginine decarboxylase, and it is hydrolyzed to urea and putrescine by agmatinase. Recently, we have described a new protein that also hydrolyzes agmatine, agmatinase-like protein (ALP), which was identified through immunohistochemical analysis in the hypothalamus and hippocampus of rats. However, its sequence differs greatly from all known agmatinases and does not contain the typical Mn(2+) ligands associated with the urea hydrolase family of proteins. ALP has a LIM-like domain close to its carboxyl terminus, and the removal of which results in a truncated variant with a tenfold increased k cat value and a threefold decreased K m value for agmatine. Analysis of the gene database revealed several transcripts, denominated LIMCH1 isoforms, with extreme 3' sequences identical to ALP. Limch1 gene products have been described as members of a multi-domain family of proteins with the biggest isoform containing a calponin homology (CH) domain at its N-terminus. Here, we cloned two LIMCH1 transcripts, one of 3177 bp and the other of 2709 bp (ALP contains 1569 bp) and analyzed LIMCH1 expression and distribution in rat brain using RT-PCR, Western blot and immunohistochemical analyses. LIMCH1 was detected mainly in the hypothalamic and hippocampal regions, which is similar to the distribution of ALP and agmatine in brain. In addition, we cloned and expressed both isoforms in E. coli and confirmed that they were catalytically active on agmatine with kinetic parameters similar to ALP. LIM domain-truncated variants of both isoforms moderately increased the k cat and catalytic efficiency. Thus, we propose that LIMCH1 is useful to regulate the intracellular concentrations of the neurotransmitter/neuromodulator, agmatine. PMID- 26678505 TI - Somatosensory temporal discrimination is prolonged during migraine attacks. AB - BACKGROUND AND OBJECTIVE: Symptoms and signs of sensorial disturbances are characteristic features of a migraine headache. Somatosensory temporal discrimination measures the temporal threshold to perceive two separate somaesthetic stimuli as clearly distinct. This study aimed to evaluate somaesthetic perception in migraine patients by measuring the somatosensory temporal discrimination thresholds. METHODS: The study included 12 migraine patients without aura and 12 volunteers without headache. Somatosensory temporal discrimination threshold (STDT) values were measured in the face (V3) and hands (C7) during a lateralized headache attack and the headache-free interictal period. The disease duration, pain intensity, phonophobia, photophobia, nausea, vomiting, and brush allodynia were also recorded during the migraine attack. RESULTS: STDT values were within normal limits and not different between the control group and the interictal period in migraine patients. Compared to the headache-free period, STDT values during the attack were significantly prolonged in the contralateral hand (C7) (155.7 +/- 84.2 vs 40.6 +/- 16.1 ms [P < .001]), ipsilateral hand (C7) (88.6 +/- 51.3 vs 31.4 +/- 14.2 ms [P < 0.001]), contralateral face (V3) (65.5 +/- 35.4 vs 37.6 +/- 22.2 ms [P = .006]) and ipsilateral face (V3) (104.1 +/- 44.5 vs 37.5 +/- 21.4 ms [P < 0.001]) according to the lateralization of the headache. Ictal STDT values of the contralateral hand and ipsilateral face were significantly increased compared to that of the ipsilateral hand and contralateral face (155.7 +/- 84.2 ms vs 88.6 +/- 5.1.3 ms [P = .001], 104.1 +/- 44.5 ms vs 65.5 +/- 35.4 ms [P = 0.001]). No allodynia was detected in the areas that were tested for somatosensory temporal discrimination. The visual analog scale scores were correlated with the somatosensory temporal discrimination thresholds of the contralateral hand (r = 0.602, P = .038), whereas no correlation was detected between the somatosensory temporal discrimination thresholds and disease duration, brush allodynia in the forehead, phonophobia, photophobia, nausea and vomiting. CONCLUSION: The study demonstrates for the first time that somatosensory temporal discrimination thresholds are elevated during migraine attacks. A transient disruption of the central processing of somaesthetic stimuli during the lateralized migraine attack may provide additional information to understand the mechanisms of the cognitive and sensory perception impairment associated with migraine headache and may have diagnostic value. PMID- 26678504 TI - Novel subcellular localization of the DNA helicase Twinkle at the kinetochore complex during mitosis in neuronal-like progenitor cells. AB - During mitosis, the kinetochore, a multi-protein structure located on the centromeric DNA, is responsible for proper segregation of the replicated genome. More specifically, the outer kinetochore complex component Ndc80/Hec1 plays a critical role in regulating microtubule attachment to the spindle for accurate sister chromatid segregation. In addition, DNA helicases play a key contribution for precise and complete disjunction of sister chromatids held together through double-stranded DNA catenations until anaphase. In this study, we focused our attention on the nuclear-encoded DNA helicase Twinkle, which functions as an essential helicase for replication of mitochondrial DNA. It regulates the copy number of the mitochondrial genome, while maintaining its integrity, two processes essential for mitochondrial biogenesis and bioenergetic functions. Although the majority of the Twinkle protein is imported into mitochondria, a small fraction remains cytosolic with an unknown function. In this study, we report a novel expression pattern of Twinkle during chromosomal segregation at distinct mitotic phases. By immunofluorescence microscopy, we found that Twinkle protein colocalizes with the outer kinetochore protein HEC1 as early as prophase until late anaphase in neuronal-like progenitor cells. Thus, our collective results have revealed an unexpected cell cycle-regulated expression pattern of the DNA helicase Twinkle, known for its role in mtDNA replication. Therefore, its recruitment to the kinetochore suggests an evolutionary conserved function for both mitochondrial and nuclear genomic inheritance. PMID- 26678506 TI - Large scale patterns of abundance and distribution of parasites in Mexican bumblebees. AB - Bumblebees are highly valued for their pollination services in natural ecosystems as well as for agricultural crops. These precious pollinators are known to be declining worldwide, and one major factor contributing to this decline are infections by parasites. Knowledge about parasites in wild bumblebee populations is thus of paramount importance for conservation purposes. We here report the geographical distribution of Crithidia and Nosema, two common parasites of bumblebees, in a yet poorly investigated country: Mexico. Based on sequence divergence of the Cytochrome b and Glycosomal glyceraldehyde phosphate deshydrogenase (gGPDAH) genes, we discovered the presence of a new Crithidia species, which is mainly distributed in the southern half of the country. It is placed by Bayesian inference as a sister species to C. bombi. We suggest the name Crithidia mexicana for this newly discovered organism. A population of C. expoeki was encountered concentrated on the flanks of the dormant volcanic mountain, Iztaccihuatl, and microsatellite data showed evidence of a bottleneck in this population. This study is the first to provide a large-scale insight into the health status of endemic bumblebees in Mexico, based on a large sample size (n=3,285 bees examined) over a variety of host species and habitats. PMID- 26678507 TI - Identification of microRNA-like small RNAs from fungal parasite Nosema ceranae. AB - We previously found transcripts encoding Dicer and Argonaute which are involved in the production of microRNAs, in the honey bee parasite Nosema ceranae. In order to identify microRNAs in N. ceranae, we sequenced small RNAs from midgut tissues of infected honey bees at 24 h intervals for 6 days post infection, covering the complete reproduction cycle for this intracellular parasite. We predicted six microRNA-like small RNAs, all of which were confirmed via RT-qPCR assays. This is the first evidence for microRNA-like small RNAs generated by a microsporidian species, providing new insights into host-parasite interactions involving this widespread taxonomic group. PMID- 26678510 TI - Recurrent cutaneous eosinophilic vasculitis. PMID- 26678511 TI - The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production. AB - As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP >= 5 mg/l (28 v. 12%; P=0.005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-gamma responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3.97; 95% CI 1.44, 10.90) but not in males (GMR 0.44; 95% CI 0.14, 1.42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS. PMID- 26678512 TI - Neural substrates of rapid eye movement sleep behavior disorder in Parkinson's disease. AB - OBJECTIVES: To investigate neural substrates of symptomatic rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease (PD) by analyzing brain changes based on both hypothesis-free and hypothesis-driven neuroimaging analyses. METHODS: A total of 63 subjects (14 PDRBD-, 24 PDRBD+, and 25 age matched healthy controls = HC) were enrolled in this study. RBD was defined by RBD screening questionnaire with video-polysomnographic confirmation. All subjects underwent volumetric and diffusion tensor imaging. The whole brain gray- and white-matter changes were analyzed and the central ascending cholinergic pathway involving the pedunculopontine nucleus and thalamus was compared with a region-of-interest analysis and probabilistic tractography. RESULTS: The PDRBD+ group showed decreased gray matter volume of the left posterior cingulate and hippocampus compared to the PDRBD- and additional gray matter decrease in the left precuneus, cuneus, medial frontal gyrus, postcentral gyrus and both inferior parietal lobule compared to the HC group (uncorrected p < 0.001, k = 50). There were no significant differences in white matter changes between the PDRBD- and PDRBD+ groups both by fractional anisotropy and mean diffusivities. However, both PD groups showed widespread changes by fractional anisotropy reductions and mean diffusivity increments compared to HC (p < 0.05 corrected). There were no significant differences in tract-based spatial statistics and the normalized tract volumes as well as the diffusion indices of both the thalamus and pedunculopontine nuclei among the study groups. CONCLUSIONS: The appearance of RBD in PD may be related to regional gray matter changes in the left posterior cingulate and hippocampus but not localized to the brainstem. PMID- 26678513 TI - Balancing Benefits and Risks of Immortal Data: Participants' Views of Open Consent in the Personal Genome Project. AB - An individual's health, genetic, or environmental-exposure data, placed in an online repository, creates a valuable shared resource that can accelerate biomedical research and even open opportunities for crowd-sourcing discoveries by members of the public. But these data become "immortalized" in ways that may create lasting risk as well as benefit. Once shared on the Internet, the data are difficult or impossible to redact, and identities may be revealed by a process called data linkage, in which online data sets are matched to each other. Reidentification (re-ID), the process of associating an individual's name with data that were considered deidentified, poses risks such as insurance or employment discrimination, social stigma, and breach of the promises often made in informed-consent documents. At the same time, re-ID poses risks to researchers and indeed to the future of science, should re-ID end up undermining the trust and participation of potential research participants. The ethical challenges of online data sharing are heightened as so-called big data becomes an increasingly important research tool and driver of new research structures. Big data is shifting research to include large numbers of researchers and institutions as well as large numbers of participants providing diverse types of data, so the participants' consent relationship is no longer with a person or even a research institution. In addition, consent is further transformed because big data analysis often begins with descriptive inquiry and generation of a hypothesis, and the research questions cannot be clearly defined at the outset and may be unforeseeable over the long term. In this article, we consider how expanded data sharing poses new challenges, illustrated by genomics and the transition to new models of consent. We draw on the experiences of participants in an open data platform-the Personal Genome Project-to allow study participants to contribute their voices to inform ethical consent practices and protocol reviews for big data research. PMID- 26678514 TI - Lenvatinib: Role in thyroid cancer and other solid tumors. AB - Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet derived growth factor receptor alpha (PDGFRalpha). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer. PMID- 26678515 TI - SpliceJumper: a classification-based approach for calling splicing junctions from RNA-seq data. AB - BACKGROUND: Next-generation RNA sequencing technologies have been widely applied in transcriptome profiling. This facilitates further studies of gene structure and expression on the genome wide scale. It is an important step to align reads to the reference genome and call out splicing junctions for the following analysis, such as the analysis of alternative splicing and isoform construction. However, because of the existence of introns, when RNA-seq reads are aligned to the reference genome, reads can not be fully mapped at splicing sites. Thus, it is challenging to align reads and call out splicing junctions accurately. RESULTS: In this paper, we present a classification based approach for calling splicing junctions from RNA-seq data, which is implemented in the program SpliceJumper. SpliceJumper uses a machine learning approach which combines multiple features extracted from RNA-seq data. We compare SpliceJumper with two existing RNA-seq analysis approaches, TopHat2 and MapSplice2, on both simulated and real data. Our results show that SpliceJumper outperforms TopHat2 and MapSplice2 in accuracy. The program SpliceJumper can be downloaded at https://github.com/Reedwarbler/SpliceJumper. PMID- 26678516 TI - Variant rs2237892 of KCNQ1 Is Potentially Associated with Hypertension and Macrovascular Complications in Type 2 Diabetes Mellitus in A Chinese Han Population. AB - KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus (T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism (SNP) rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20 1.75). Genotypes CT (OR, 1.97; 95% CI, 1.24-3.15) and CC (OR, 2.49; 95% CI, 1.57 3.95) were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure (P=0.015), prevalence of hypertension (P=0.037), and risk of macrovascular disease (OR, 2.10; CI, 1.00-4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 is associated with an increased risk for T2DM and might contribute to the higher incidence of hypertension and macrovascular complications in patients with T2DM carrying the risk allele C though it needs further to be confirmed in a larger population. PMID- 26678517 TI - Influence of preoperative pain intensity on postoperative pain after root canal treatment: A prospective clinical study. AB - OBJECTIVES: The aim of this prospective study was to investigate the correlation between the intensity of preoperative pain and the presence of postoperative pain, taking into account the variables sex, tooth type, arch, and tooth vitality. METHODS: Two hundred and seventy patients with pulpal pathology who were scheduled for routine endodontic treatment were enrolled in this study. Conventional endodontic treatment was carried out in a single visit. The chemomechanical preparation of root canals was performed with ProTaper instruments, and canals were obturated with a warm gutta-percha obturation technique. A structured questionnaire was used to record data on sex, age, type of tooth, location and pulp diagnosis. Patients were asked to record their preoperative and postoperative pain using a 10-cm visual analogue scale (VAS). Postoperative pain and the need for analgesic consumption were assessed at 4, 8, 16, 24, 48 and 72h post-treatment. The data were analyzed using the Mann-Whitney U and chi-square test, and the significance was set at P<.05. RESULTS: The mean level of pain after root canal treatment was 2.58+/-2.80 on a VAS between 0 and 10. Variables that were associated with a higher preoperative pain intensity (female, mandible and molar) also had a higher value of postoperative pain (P>.05). CONCLUSIONS: Within the limitations of this study, it can be concluded that the presence of preoperative pain is the variable that most influences the prevalence of postoperative pain. CLINICAL SIGNIFICANCE: Pain management should be an integral part of dental treatment. The present study analyses the incidence of postoperative pain that should be expected by patients with different intensity of pain before root canal treatment. PMID- 26678518 TI - Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial. AB - BACKGROUND: While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose-response from the campaign was only assessed by self-report. OBJECTIVE: Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. METHODS: A 3 month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. RESULTS: In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. CONCLUSIONS: The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non smokers and further increasing quit attempts among smokers, especially African Americans. PMID- 26678519 TI - Using an accumulation of deficits approach to measure frailty in a population of home care users with intellectual and developmental disabilities: an analytical descriptive study. AB - BACKGROUND: The aging population of adults with intellectual and developmental disabilities (IDD) is growing. In the general aging population, frailty is commonly used to predict adverse health outcomes, including hospital use, death, and admission to long-term care. However, existing frailty measures are less appropriate for aging persons with IDD, given their pre-existing conditions and limitations. An accumulation of deficits approach, which is now widely used to describe frailty in the general population, may be more suitable for persons with IDD. Frailty measures specific to persons with IDD have not been widely studied. METHODS: Using pre-determined criteria, a frailty index (FI) specific to persons with IDD was developed based on items in the Resident Assessment Instrument - Home Care (RAI-HC), and using the assessments of 7,863 individuals with IDD in Ontario (aged 18-99 years) admitted to home care between April 1(st), 2006 and March 31(st), 2014. FI scores were derived by dividing deficits present by deficits measured, and categorized into meaningful strata using stratum-specific likelihood ratios. A multinomial logistic regression model identified associations between frailty and individual characteristics. RESULTS: The resulting FI is comprised of 42 deficits across five domains (physiological, psychological, cognitive, social and service use). The mean FI score was 0.22 (SD = 0.13), equivalent to 9 deficits. Over half of the cohort was non-frail (FI score < 0.21), while the remaining were either pre-frail (21 %, FI score between 0.21 and 0.30) or frail (27 %, FI score > 0.30). Controlling for individual characteristics, women were more likely to be frail compared to men (OR = 1.39, 95 % CI: 1.23-1.56). Individuals who were frail were significantly more likely to have a caregiver who was unable to continuing caring (OR = 1.86, 95 % CI: 1.55 2.22) or feeling distressed (OR = 1.54, 95 % CI: 1.30-1.83). Living with a family members was significantly protective of frailty (OR = 0.35, 95 % CI: 0.29-0.41), compared to living alone. CONCLUSIONS: Using the FI to identify frailty in adults with IDD is feasible and can be incorporated into existing home care assessments. This could offer case managers assistance in identifying at-risk individuals. Future analyses should evaluate this measure's ability to predict future adverse outcomes. PMID- 26678520 TI - Generation of an 870 kb deletion encompassing the Skt/Etl4 locus by combination of inter- and intra-chromosomal recombination. AB - BACKGROUND: Etl4(lacZ) (Enhancer trap locus 4) and Skt(Gt) (Sickle tail) are lacZ reporter gene integrations into the same locus on mouse chromosome 2 targeting a gene that is expressed in the notochord of early embryos and in multiple epithelia during later development. Both insertions caused recessive mutations that resulted exclusively in mild defects in the caudal vertebral column. Since notochord-derived signals are essential for formation of the vertebral column the phenotypes suggested that the lacZ insertions interfered with some notochord dependent aspect of vertebral development. As both insertions occurred in introns it was unclear whether they represent hypomorphic alleles or abolish gene function. Here, we have generated a definitive null allele of the Skt/Etl4 gene and analysed homozygous mutants. RESULTS: We have introduced loxP sites into three positions of the gene based on additional upstream exons that we identified, and deleted approximately 870 kb of the locus by a combination of inter- and intra-chromosomal Cre-mediated recombinations in the female germ line of mice. This deletion removes about 90 % of the coding region and results in the loss of the SKT/ETL4 protein. Similar to the Etl4(lacZ) and Skt(Gt) alleles our deletion mutants are viable and fertile and show only mild defects in caudal vertebrae due to abnormal intervertebral disc development, although with higher penetrance. No other tissue with Skt/Etl4 expression that we analysed showed obvious defects. CONCLUSION: The complete loss of Skt/Etl4 function affects only development of caudal notochord derivatives and is compensated for in its other expression domains. PMID- 26678521 TI - Pharmacological modulation of dietary lipid-induced cerebral capillary dysfunction: Considerations for reducing risk for Alzheimer's disease. AB - An increasing body of evidence suggests that cerebrovascular dysfunction and microvessel disease precede the evolution of hallmark pathological features that characterise Alzheimer's disease (AD), consistent with a causal association for onset or progression. Recent studies, principally in genetically unmanipulated animal models, suggest that chronic ingestion of diets enriched in saturated fats and cholesterol may compromise blood-brain barrier (BBB) integrity resulting in inappropriate blood-to-brain extravasation of plasma proteins, including lipid macromolecules that may be enriched in amyloid-beta (Abeta). Brain parenchymal retention of blood proteins and lipoprotein bound Abeta is associated with heightened neurovascular inflammation, altered redox homeostasis and nitric oxide (NO) metabolism. Therefore, it is a reasonable proposition that lipid-lowering agents may positively modulate BBB integrity and by extension attenuate risk or progression of AD. In addition to their robust lipid lowering properties, reported beneficial effects of lipid-lowering agents were attributed to their pleiotropic properties via modulation of inflammation, oxidative stress, NO and Abeta metabolism. The review is a contemporary consideration of a complex body of literature intended to synthesise focussed consideration of mechanisms central to regulation of BBB function and integrity. Emphasis is given to dietary fat driven significant epidemiological evidence consistent with heightened risk amongst populations consuming greater amounts of saturated fats and cholesterol. In addition, potential neurovascular benefits associated with the use of hypolipidemic statins, probucol and fenofibrate are also presented in the context of lipid-lowering and pleiotropic properties. PMID- 26678522 TI - alpha1 -AR agonist induced piloerection protects against the development of traction alopecia. AB - Traction alopecia is hair loss that occurs after persistent pulling (e.g., during cosmetic procedures) on the roots of hair over time. Unlike plucking, which is painful, persistent pulling may go unnoticed until a patient presents with either bald spots or diffuse telogen shedding. Each hair follicle in the scalp contains an arrector pili muscle that, when contracted, erects the hair. The smooth muscle in the arrector pili expresses alpha1 adrenergic receptors (alpha1 -AR). As such, we hypothesized that contraction of the arrector pili muscle via an alpha1 -AR agonist would increase the threshold of force required to pluck hair during cosmetic procedures. Female subjects, ages 18-40, were recruited to study the effect of topically applied phenylephrine, a selective alpha1 -AR agonist, on epilation force and hair shedding during cosmetic procedures. In our blinded study, 80% of subjects demonstrated reduced shedding on days using phenylephrine compared to days using a placebo solution. The average reduction in hair loss was approximately 42%. In addition, the force threshold required for epilation increased by approximately 172% following topical phenylephrine application. To our knowledge this is the first study demonstrating the utility of alpha1 -AR agonists in the treatment of traction alopecia and hair shedding during cosmetic procedures. PMID- 26678523 TI - The complete mitochondrial genome of the cryptic species C of Aneura pinguis. AB - The structure of the Aneura pinguis mitochondrial genome (GenBank accession no. NC_026901) is similar to that of closely related Metzgeriales species: it has a total length of 165 603 bp, the base composition of the mitogenome is the following: A (26.2%), C(23.6%), G(23.8%), and T(26.4%). The A. piguis mitochondrial genome contains 69 genes. A complete mitochondrial genome sequence of A. pinguis will help better to understand mitogenome structure and content among Metzgeriales order. PMID- 26678524 TI - Performance demonstration of 4pibeta(LS)-gamma coincidence counting system for standardization of radionuclides with complex decay scheme. AB - A standardization of (134)Cs and (131)I was carried out in order to demonstrate the performance and applicability of the 4pibeta(LS)-gamma coincidence counting system for standardization of radionuclides with complex decay scheme. The coincidence analyzer, capable of analyzing coincidence between beta and two gamma windows simultaneously, was developed and used for the standardization. The use of this dual coincidence analyzer has reduced the total experimental time by half. The activity concentrations obtained using the 4pibeta(LS)-gamma coincidence counting system, a 4pibeta(PC)-gamma coincidence counting system, and the CIEMAT/NIST method are in excellent agreement with each other within uncertainty limits and hence demonstrates its performance for standardization of radionuclides decaying with complex decay scheme. Hence use of this 4pibeta(LS) gamma coincidence counting system can be an alternative method suitable to standardize radionuclides with complex decay scheme with acceptable precision. PMID- 26678525 TI - Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial. AB - BACKGROUND: Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 MUmol/L) at 6 months. METHODS: Levels of cobalamin, folate, riboflavin and pyridoxal 5' phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 MUmol/L were enrolled in a double blind randomized controlled trial to receive 400 MUg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month. RESULTS: Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03). CONCLUSIONS: The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01201005. PMID- 26678526 TI - Pancreatic enucleation using the da Vinci robotic surgical system: a report of 26 cases. AB - BACKGROUND: As a tissue-sparing procedure, pancreatic enucleation has become an alternative for benign or borderline pancreatic tumours; it has been proved to be safe and feasible. To date, a large sample size of robotic pancreatic enucleation has not been reported. This study aimed to discuss the clinical evaluation and postoperative complications after robotic pancreatic enucleation and compare it with open surgery. METHODS: Patients who underwent robotic or open pancreatic enucleation during December 2010-December 2014 at Shanghai Ruijin Hospital, affiliated with the Shanghai Jiaotong University School of Medicine in China, were included. Clinical data were collected and analysed. RESULTS: Patients were divided into an open group and a robotic group: 26 patients underwent robotic pancreatic enucleation, of whom 13 patients were female. The mean age was 51.7 years, the operation time was 125.7 +/- 58.8 min, blood loss was 49.4 +/- 33.4 ml and mean tumour size was 18.8 +/- 7.9 mm; 17 patients underwent open pancreatic enucleation, of whom 11 were female. The mean age was 54.6 +/- 17.2 min, blood loss was 198.5 +/- 70.7 ml and mean tumour size was 3.5 +/- 1.9 cm. Pathology included insulinomas, intrapancreatic mucinous neoplasmas (IPMNs), pancreatic neuro-endocrine tumours (PNETs), solid pseudopapillary tumours (SPTs) and serous cystadenomas (SCAs). Robotic pancreatic enucleations were associated with less trauma, shorter operation time, less blood loss and faster wound recovery compared with open pancreatic enucleation. Pancreatic fistulas (PFs) were the main complication that occurred in the robotic group; infection also occurred in the open group. All patients recovered after effective drainage and the use of somatostatin. The mean follow-up time was 25 months. No recurrence was discovered, and one patient in the open group suffered endocrine insufficiency. CONCLUSION: Robotic pancreatic enucleation is a safe and effective surgical procedure for pancreatic benign and borderline tumours. It produces less trauma than open pancreatic enucleation and might extend the indications for enucleation. The PF rate after surgery is still high and a long-term follow-up needs to be performed. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26678527 TI - Correction to High-Efficiency Colloidal Quantum Dot Photovoltaics via Robust Self Assembled Monolayers. PMID- 26678528 TI - The Exosome - A Naturally Secreted Nanoparticle and its Application to Wound Healing. AB - Wound healing is a complex process and often delayed in patients with underlying chronic conditions. The cost of wound care is a significant burden to the society, warranting new techniques to prompt wound healing. Several studies have reported on the beneficial effects of mesenchymal stem cells (MSCs) function in recruiting host cells, releasing secretory factors and matrix proteins thereby increasing wound heal. These secrete bioactive trophic factors from MSCs also includes extracellular vesicles (EVs) or exosomes. Recent studies have shown that EVs are one of the key secretory products of MSCs mediating cell-to-cell communication to enhance wound healing. Current knowledge related to the potential use of EVs in wound healing is reviewed and the promising future for EVs - a naturally secreted nanoparticle - as an alternative to cell-based therapy is discussed. PMID- 26678530 TI - Is there a link between diabetes and cholesterol metabolism? PMID- 26678529 TI - Effect of the acute general surgical unit: a regional perspective. AB - BACKGROUND: Acute surgical units have gained favour in Australia and New Zealand. However, there is a lack of evidence regarding their effectiveness in regional centres. We aim to investigate the effect of the introduction of the Acute General Surgical Unit (AGSU) on the outcomes for patients undergoing emergency appendicectomies or cholecystectomies in a regional hospital. METHODS: AGSU was introduced in March 2012. We conducted a retrospective comparison analysis of patients admitted 2 years prior to and 2 years after the introduction of AGSU. Primary outcomes included length of stay, time to theatre, after hours and overnight operating. Secondary outcomes included negative appendicectomy rate, conversion to open cholecystectomy and bile duct injuries. RESULTS: No difference was seen between pre and post-AGSU introduction in median time to theatre in the appendicectomy group (8.00 h versus 9.24 h) or cholecystectomy group (17.63 h versus 17.75 h). Additionally, there was no difference between median length of stay in the appendicectomy group (47.52 h versus 48.00 h) or the cholecystectomy group (71.50 h versus 70.67 h). Night operating was significantly reduced in the positive appendicectomy group (4.4% versus 9.1%, P = 0.027) and the overall cholecystectomy group (0.43% versus 3.4%, P = 0.035), however overall after hours operating remained equivalent. CONCLUSIONS: The introduction of the AGSU unit led to a significant reduction in overnight operating, which may improve patient outcomes and surgeon satisfaction. Length of stay and time to theatre did not change. Future directions include further research into the impact of theatre access on emergency surgery outcomes. PMID- 26678532 TI - Fighting sinus-derived Staphylococcus aureus biofilms in vitro with a bacteriophage-derived muralytic enzyme. AB - BACKGROUND: Staphylococcus aureus biofilms are a nidus for exacerbation of infectious conditions including chronic rhinosinusitis (CRS). Resistance of biofilms to current therapeutics stresses the need for the development of novel anti-biofilm strategies. The chimeric muralytic enzyme P128 was specifically engineered to target Staphylococcal sp. by combining the cell wall binding domain of lysostaphin and the peptidoglycan-degrading murein hydrolase derived from phage K. This study assessed the anti-biofilm activity of P128 against sinus derived S. aureus. METHODS: Biofilms from S. aureus ATCC 25923 and 3 sinus derived methicillin-sensitive and methicillin-resistant CRS clinical isolates were grown for 48 hours and treated with various concentrations of P128 (0 to 100 MUg/mL) for 2 and 24 hours, using the minimum biofilm eradication concentration (MBEC) assay and Alamar Blue (AB) assay. Biofilm present on the MBEC pegs was stained with LIVE/DEAD BacLight stain, imaged using confocal scanning laser microscopy and biomass determined by COMSTAT2 computation. In the AB assay, biofilm was measured by assessing the cell viability. Results were assessed using a Kruskal-Wallis test, with a Wilcoxon post hoc test and Bonferroni correction. RESULTS: Both the MBEC and AB assay indicated that P128 was effective against in vitro S. aureus biofilms with significant reductions in biofilm of up to 95.5% at concentrations >=12.5 MUg/mL for all tested strains. CONCLUSION: The engineered chimeric endolysin P128 was observed to be an effective anti-biofilm agent against S. aureus. Further study will proceed into the appropriate application of P128 to ensure both an economically and clinically feasible preparation. PMID- 26678531 TI - Fetal growth restriction and methylation of growth-related genes in the placenta. AB - AIM: To examine the associations between fetal growth restriction (FGR) and DNA methylation of six growth-related genes in human placenta. MATERIALS & METHODS: A total of 181 mother-newborn pairs (80 FGR cases and 101 controls) were enrolled in this case-control study. Placental DNA methylation was measured by bisulfite pyrosequencing. RESULTS: DNA methylation levels of IGF2 and AHRR were positively associated with newborn birth weight and Quetelet's index, while DNA methylation levels of HSD11B2 and WNT2 were negatively associated with those fetal growth indicators. In addition, significantly elevated odds of FGR birth were associated with increasing DNA methylation of HSD11B2 and WNT2, and decreasing DNA methylation of IGF2. CONCLUSION: Our findings demonstrated that placental DNA methylation levels of IGF2, AHRR, HSD11B2 and WNT2 were associated with measures of fetal growth. PMID- 26678533 TI - Prothrombin complex concentrate for the management of severe traumatic bleeding in a patient anticoagulated with apixaban. AB - WHAT IS KNOWN AND OBJECTIVE: Given the data for four factor prothrombin complex concentrate (PCC) for vitamin K antagonist (VKA) reversal, there is great interest to determine whether PCC can improve patient outcomes in patients with bleeds associated with the newer oral anticoagulants (NOAC). CASE DESCRIPTION: We describe the case of an adult trauma patient anticoagulated with apixaban, presenting with a severe life-threatening bleed. PCC was administered at the maximum dose when the patient was determined to be refractory to supportive care with blood products. WHAT IS NEW AND CONCLUSION: Despite maximal treatment efforts, haemostasis was not achieved and the patient expired. PMID- 26678534 TI - In situ evaluation of DGT techniques for measurement of trace metals in estuarine waters: a comparison of four binding layers with open and restricted diffusive layers. AB - Four different DGT binding layers were used to make selective measurements of trace metals in coastal waters within The Broadwater (Gold Coast, Queensland). Chelex and PAMPAA (polyacrylamide-polyacrylic acid) binding layers were used to measure cations (Cd, Co, Cu, Mn, Ni, Pb, Zn), and Metsorb was used to measure anions (Al, As, Mo, Sb, V, W). A mixed binding layer (MBL) containing both Chelex and Metsorb was used to measure each of the trace metals and determine diffusive boundary layer (DBL) thicknesses. DGT measurements that were not corrected for the DBL thickness (0.049-0.087) were underestimated by 70% on average. Good agreement was observed between DGT-MBL and DGT-Chelex for measurement of Cd, Co, Cu, Ni, Pb and Zn, and between DGT-MBL and DGT-Metsorb for As, Sb and V. DGT-MBL measured significantly higher concentrations for Mn (compared with DGT-Chelex) and Al (compared with DGT-Metsorb). DGT-Chelex measured only 6-8% of Al species measured by either DGT-MBL or DGT-Metsorb. DGT-PAMPAA measurements of Cu, Pb and Al were lower than those of either DGT-MBL or DGT-Chelex varying from 74-81% for Cu to 54-70% for Pb and 51-55% for anionic Al(OH)4(-), suggesting that this binding layer may make more selective measurements. All measured trace metal concentrations were well below ANZECC water quality guidelines, except for Cu which was 2 to 10 times higher than trigger values. Each of the DGT techniques was deployed using both open and restricted diffusive layers (ODL and RDL). Most trace metal measurements were not significantly different with ODL and RDL for all binding layers. However, concentrations of Cu (CRDL/CODL = 0.68-0.75) and Al (CRDL/CODL = 0.73-0.79) were significantly different with DGT-MBL, DGT-Chelex and DGT-Metsorb. PMID- 26678535 TI - On the origins of the 'global signal' determined by functional magnetic resonance imaging in the resting state. AB - OBJECTIVE: Functional magnetic resonance imaging blood oxygen level dependent (BOLD) determinations of correlations between 'resting-state' neuronal activity in different regions of cortex have generated much interest. Determination of these correlations requires regressing out signals that are correlated in all parts of the cortex and are taken to be artefactual, such as those due to movement, respiration and cardiovascular activity. However when these are removed there still remains a 'global signal' (GS), which is taken to be of unknown physiological origin, and is regressed out by some researchers but not by others. APPROACH: We have investigated the origin of this GS using cortical models consisting of coupled networks of modules representing regions of interest. MAIN RESULTS: We show that the GS has an amplitude that is linearly related to the average correlation between the modules/voxels in the network over a large range of such correlations. The GS arises as a consequence of feedback between the modules/voxels leading to correlations in their BOLD signals. Given the relationship between the GS and the average correlations it might be anticipated that regressing out the GS during preprocessing will significantly modify the correlations subsequently determined. This is shown to be the case when comparing the connections of individual modules with that predicted by the correlations. SIGNIFICANCE: The present model shows that such correlations can arise as a consequence of the intermodular feedback connectivity without recourse to imposing a GS independent of the connectivity. Our model indicates that the GS reflects the extent of feedback pathways provided by the intermodular/inter regional connections and hence the average correlation between modules or regions of cortex. However the model has not been used to elucidate the possible contributions of a GS independent of the connectivity, which might indeed contribute to the GS of the cortex. PMID- 26678536 TI - Assessment of different washing treatments to mitigate imidacloprid and acetamaprid residues in spinach. AB - BACKGROUND: Agricultural crops treated with pesticides retain toxic residues that can cause various health disorders upon consumption. The present research project was designed to assess pesticide residues in contaminated spinach (Spinacia oleracea). The efficiency of chemical solutions (acetic acid, citric acid, hydrogen peroxide, sodium chloride and sodium carbonate) of different concentrations (% w/v) along with tap water for the dissolution of pesticide residues in spinach was studied. After various dipping treatments (T0 -T22 ) of treated spinach, imidacloprid and acetamaprid residues were determined by high performance liquid chromatography (HPLC). RESULTS: Among the solutions tested, the highest reductions in imidacloprid and acetamaprid residues respectively were 0.92 +/- 0.04 mg kg(-1) (83%) and 1.42 +/- 0.53 mg kg(-1) (87%) in treatment T6 (10% acetic acid), followed by 0.79 +/- 0.01 mg kg(-1) (69%) and 0.86 +/- 0.05 mg kg(-1) (71%) in treatment T11 (10% citric acid), while the lowest were 0.30 +/- 0.02 mg kg(-1) (27%) and 0.35 +/- 0.02 mg kg(-1) (29%) in treatment T20 (4% sodium carbonate). Moreover, treatment T1 (tap water) caused 0.27 +/- 0.00 mg kg( 1) (23%) and 0.38 +/- 05 mg kg(-1) (27%) elimination of imidacloprid and acetamaprid residues respectively. CONCLUSION: From these findings it is inferred that acetic acid and citric acid washing treatments can be used along with tap water to minimize pesticide residues in treated vegetables. (c) 2015 Society of Chemical Industry. PMID- 26678537 TI - A new model of Social Support in Bereavement (SSB): An empirical investigation with a Chinese sample. AB - Bereavement can be an extremely stressful experience while the protective effect of social support is expected to facilitate the adjustment after loss. The ingredients or elements of social support as illustrated by a new model of Social Support in Bereavement (SSB), however, requires empirical evidence. Who might be the most effective providers of social support in bereavement has also been understudied, particularly within specific cultural contexts. The present study uses both qualitative and quantitative analyses to explore these two important issues among bereaved Chinese families and individuals. The results show that three major types of social support described by the SSB model were frequently acknowledged by the participants in this study. Aside from relevant books, family and friends were the primary sources of social support who in turn received support from their workplaces. Helping professionals turned out to be the least significant source of social support in the Chinese cultural context. Differences by gender, age, and bereavement time were also found. The findings render empirical evidence to the conceptual model of Social Support in Bereavement and also offer culturally relevant guidance for providing effective support to the bereaved. PMID- 26678538 TI - The biochemical signatures of stress: A preliminary analysis of osteocalcin concentrations and macroscopic skeletal changes associated with stress in the 13th - 17th centuries black friars population. AB - OBJECTIVE: As a chemical precursor to the hard tissue changes well-studied in bioarchaeological research, osteocalcin provides a unique opportunity to assess stress via fluctuations in bone metabolism. The main objectives of this research were 1) to successfully extract osteocalcin from the Black Friars skeletal population; 2) to assess the diagenetic change between individual bone samples; and 3) to compare osteocalcin concentrations across sex, age, time period and macroscopic indicators of stress. METHODS: Twenty adult individuals were selected from the 13th-17th centuries Black Friars skeletal population with bone samples taken from the clavicle and femur. Total protein was assessed through a MicroBCA analysis with osteocalcin quantified using a Human Quantikine ELISA kit. Diagenetic change was assessed using Fourier transform infrared spectroscopy and the attenuated total reflectance method. RESULTS: Osteocalcin concentrations showed no significant differences between sex or age groups; however, between time period the post-medieval individuals showed a significant reduction of osteocalcin in both the clavicle and the femur. There were no significant differences in osteocalcin concentrations between those with and without past stress indicators and only one significant difference among the chronic indicators. The diagenetic results demonstrated a similar degree of crystallinity between all samples. CONCLUSIONS: While preliminary in nature, this study was successful in demonstrating the potential use of osteocalcin in future health related research and how the study of osteocalcin may contribute to a better understanding of how and when stress begins to affect the skeletal tissues. PMID- 26678540 TI - Biobanking genetic resources: challenges and implementation at the USDA National Animal Germplasm Program. AB - There is adequate infrastructure in the US to identify and acquire germplasm from the major beef and dairy cattle and swine breeds. However, when we venture outside these species, the same tasks become more difficult because of a lack of breed associations, databases that include genotypic and phenotypic data and low numbers of animals. Furthermore, acquisition of germplasm from non-cattle and non swine species can be difficult because these animals are often not located near the National Animal Germplasm Program, which makes collection and preservation of the samples in a timely manner that much more complicated. This problem is compounded because not all preservation protocols are optimised for field collection conditions or for all types of germplasm. Since 1999, the USDA National Animal Germplasm Program has worked to overcome these obstacles by developing policies, procedures and techniques in order to create a germplasm repository for all agricultural species (wild and domesticated) in the US. Herein, we describe these activities and illustrate them via a case study on how our efforts collecting Navajo-Churro sheep have created a secure backup of germplasm and how we specifically overcome these issues as they relate to rare and minor breeds of agricultural species. PMID- 26678541 TI - Post-tonsillectomy pain control: consensus or controversy? AB - Pediatric post-tonsillectomy analgesia continues to be highly debated and an area of active research. Tonsillectomy pain can lead to significant patient morbidity, and incur potentially avoidable healthcare costs. Moreover, the various analgesic classes, each present their own risk profiles and unique side effects when used in children post-tonsillectomy. This review delineates the clinical and pathophysiological basis for post-tonsillectomy pain, types of analgesics and their risk profiles, as well as special considerations in this clinical population and a review of alternative analgesic treatment options. This article presents a summary of recent literature and discusses evidence-based management options to aid medical and allied health professionals who may encounter these patients. PMID- 26678539 TI - Mixed Lineage Leukemia 5 (MLL5) Protein Stability Is Cooperatively Regulated by O GlcNac Transferase (OGT) and Ubiquitin Specific Protease 7 (USP7). AB - Mixed lineage leukemia 5 (MLL5) protein is a trithorax family histone 3 lysine 4 (H3K4) methyltransferase that regulates diverse biological processes, including cell cycle progression, hematopoiesis and cancer. The mechanisms by which MLL5 protein stability is regulated have remained unclear to date. Here, we showed that MLL5 protein stability is cooperatively regulated by O-GlcNAc transferase (OGT) and ubiquitin-specific protease 7 (USP7). Depletion of OGT in cells led to a decrease in the MLL5 protein level through ubiquitin/proteasome-dependent proteolytic degradation, whereas ectopic expression of OGT protein suppressed MLL5 ubiquitylation. We further identified deubiquitinase USP7 as a novel MLL5 associated protein using mass spectrometry. USP7 stabilized the MLL5 protein through direct binding and deubiquitylation. Loss of USP7 induced degradation of MLL5 protein. Conversely, overexpression of USP7, but not a catalytically inactive USP7 mutant, led to decreased ubiquitylation and increased MLL5 stability. Co-immunoprecipitation and co-immunostaining assays revealed that MLL5, OGT and USP7 interact with each other to form a stable ternary complex that is predominantly located in the nucleus. In addition, upregulation of MLL5 expression was correlated with increased expression of OGT and USP7 in human primary cervical adenocarcinomas. Our results collectively reveal a novel molecular mechanism underlying regulation of MLL5 protein stability and provide new insights into the functional interplay among O-GlcNAc transferase, deubiquitinase and histone methyltransferase. PMID- 26678542 TI - Investigation of neuropsychological characteristics of very mild and mild dementia with Lewy bodies. AB - INTRODUCTION: The study aimed to compare the profile of very mild and mild dementia with Lewy bodies (DLB) patients with disease duration up to 5 years in order to find markers for faster progression in this early stage. METHOD: We investigated 45 DLB patients with disease duration up to 5 years and 22 normal controls. DLB patients were divided into two subgroups on the basis of the Mini Mental State Examination (MMSE): very mild and mild. RESULTS: Compared to normal controls, very mild DLB patients show significant deficits on tests for attention/executive functions, language, visuospatial/constructional abilities, and retrieval of the episodic memory. In addition, mild DLB (mDLB) patients show a significantly lower score on recall and recognition of the Free and Cued Selective Reminding Test (FCSRT), Trail Making Test Part B (TMT-B), Stroop test, verbal fluency, and Clock Drawing Test than did very mild DLB (vmDLB) patients. Patients with mDLB also have more visual hallucinations, but not significant motor differences compared to vmDLB. CONCLUSIONS: In the present work we found that faster progression to the mild DLB stage in the first few years of the disease is mainly related to deterioration of memory, attention/executive functions, and visuospatial abilities, as well as an increased frequency of visual hallucinations. PMID- 26678543 TI - Rebuttal to the Formal Comment on Schorr et al. (2014) submitted by Tyack et al. (2015). PMID- 26678544 TI - The Phenotypic and Functional Features of Human M2 Macrophages Generated Under Low Serum Conditions. AB - The phenotypic and functional features of human M2 macrophages, in particular, their immunosuppressive activity, can considerably vary depending on M2 polarizing stimulus. This study was aimed at the investigation of cytokine production and pro-apoptogenic/inhibitory molecule expression in macrophages generated with GM-CSF using either standard conditions (M1) or deficiency of serum/growth factors (M2-LS cells). In contrast to M1, M2-LS cells were characterized by an enhanced content of CD206(+), B7-H1(+), FasL(+) and TRAIL(+) cells along with a decreased production of IFN-gamma, IL-5, IL-6, IL-13, TNF alpha, IL-17 and MCP-1. In addition, M2-LS exhibited a lower T cell stimulatory activity in MLC that was associated with the higher numbers of apoptotic and the lower numbers of proliferating T cells. B7-H1 plays a key role in M2-LS-mediated cytotoxic effects as the neutralization of B7-H1 reduces the apoptosis-inducing activity of M2-LS, while the blocking of CD206 and TRAIL reduces the cytostatic activity of M2 macrophages. PMID- 26678545 TI - Health State Utility Value in Chronic Obstructive Pulmonary Disease (COPD); The Challenge of Heterogeneity: A Systematic Review and Meta-Analysis. AB - Chronic obstructive pulmonary disease (COPD) has a considerable impact on quality of life and well-being of patients. Health state utility value (HSUV) is a recognized measure for health economic appraisals and is extensively used as an indicator for decision-making studies. This study is a systematic review of literature aimed to estimate mean utility value in COPD using meta-analysis and explore degree of heterogeneity in the utility values across a variety of clinical and study characteristic. The literature review covers studies that used EQ-5D to estimate utility value for patient level research in COPD. Studies that reported utility values elicited by EQ-5D in COPD patients were selected for random-effect meta-analysis addressing inter-study heterogeneity and subgroup analyses. Thirty-two studies were included in the general utility meta-analysis. The estimated general utility value was 0.673 (95% CI 0.653 to 0.693). Meta analyses of COPD stages utility values showed influence of airway obstruction on utility value. The utility values ranged from 0.820 (95% CI 0.767 to 0.872) for stage I to 0.624 (95% CI 0.571 to 0.677) for stage IV. There was substantial heterogeneity in utility values: I(2) = 97.7%. A more accurate measurement of utility values in COPD is needed to refine valid and generalizable scores of HSUV. Given the limited success of the factors studied to reduce heterogeneity, an approach needs to be developed how best to use mean utility values for COPD in health economic evaluation. PMID- 26678547 TI - Abstracts - Scientific Session 1. PMID- 26678548 TI - Sclerotherapy of Diffuse and Infiltrative Venous Malformations of the Hand and Distal Forearm. AB - PURPOSE: Venous malformations (VM) involving the hand and forearm often lead to chronic pain and dysfunction, and the threshold for treatment is high due to the risk of nerve and skin damage, functional deterioration and compartment syndrome. The purpose of this study is to demonstrate that sclerotherapy of diffuse and infiltrative VM of the hand is a safe and effective therapy. MATERIALS AND METHODS: A retrospective review of all patients with diffuse and infiltrative VM of the hand and forearm treated with sclerotherapy from 2001 to 2014 was conducted. All VM were diagnosed during the clinical visit by a combination of physical examination and imaging. Sclerotherapy was performed under imaging guidance using ethanol and/or sodium tetradecyl sulfate foam. Clinical notes were reviewed for signs of treatment response and complications, including skin blistering and nerve injury. RESULTS: Seventeen patients underwent a total of 40 sclerotherapy procedures. Patients were treated for pain (76%), swelling (29%) or paresthesias (6%). Treatments utilized ethanol (70%), sodium tetradecyl sulfate foam (22.5%) or a combination of these (7.5%). Twenty-four percent of patients had complete resolution of symptoms, 24% had partial relief of symptoms without need for further intervention, and 35% had some improvement after initial treatment but required additional treatments. Two skin complications were noted, both of which resolved. No motor or sensory loss was reported. CONCLUSION: Sclerotherapy is a safe and effective therapy for VM of the hand with over 83% of patients experiencing relief. PMID- 26678546 TI - Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior. AB - The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild-derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]-element insertion mutants in Sema-5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their coisogenic wild-type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, showing extensive nonadditive genetic variation. We performed genome-wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the nonadditive genetic variance. Candidate genes could be placed in interaction networks. Several candidate modifiers are associated with neural development. Analyses of mutants of candidate epistatic partners with neur (merry-go-round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema-5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared with coisogenic controls. Thus, integrating genome-wide analyses of natural variants with mutations at defined genomic locations in a common coisogenic background can unmask specific epistatic modifiers of behavioral phenotypes. PMID- 26678549 TI - Microdosed Lipid-Coated (67)Ga-Magnetite Enhances Antigen-Specific Immunity by Image Tracked Delivery of Antigen and CpG to Lymph Nodes. AB - Development of vaccines to prevent and treat emerging new pathogens and re emerging infections and cancer remains a major challenge. An attractive approach is to build the vaccine upon a biocompatible NP that simultaneously acts as accurate delivery vehicle and radiotracer for PET/SPECT imaging for ultrasensitive and quantitative in vivo imaging of NP delivery to target tissues/organs. Success in developing these nanovaccines will depend in part on having a "correct" NP size and accommodating and suitably displaying antigen and/or adjuvants (e.g., TLR agonists). Here we develop and evaluate a NP vaccine based on iron oxide-selective radio-gallium labeling suitable for SPECT((67)Ga)/PET((68)Ga) imaging and efficient delivery of antigen (OVA) and TLR 9 agonists (CpGs) using lipid-coated magnetite micelles. OVA, CpGs and rhodamine are easily accommodated in the hybrid micelles, and the average size of the construct can be controlled to be ca. 40 nm in diameter to target direct lymphatic delivery of the vaccine cargo to antigen presenting cells (APCs) in the lymph nodes (LNs). While the OVA/CpG-loaded construct showed effective delivery to endosomal TLR 9 in APCs, SPECT imaging demonstrated migration from the injection site to regional and nonregional LNs. In correlation with the imaging results, a range of in vitro and in vivo studies demonstrate that by using this microdosed nanosystem the cellular and humoral immune responses are greatly enhanced and provide protection against tumor challenge. These results suggest that these nanosystems have considerable potential for image-guided development of targeted vaccines that are more effective and limit toxicity. PMID- 26678550 TI - Complete mitochondrial genome and phylogenetic relationship analysis of Garrulax affinis (Passeriformes, Timaliidae). AB - Garrulax affinis was a medium-sized bird of Timaliidae, and we got its complete mitochondrial genome by the polymerase chain reaction method (PCR). The genome (17 856 in length), it contained 13 protein-coding genes, 2 rRNA (12S and 16S) genes, 2 tRNA genes, 2 control regions (D-loop). All protein-coding, rRNA, and tRNA genes were similar to other Passeriformes in gene arrangement and composition. In 13 PCGs, 12 were initiated with ATG, only COI was GTG, and stopped by five types of stop codons. We constructed a phylogenetic tree based on 13 PCGs of G. affinis and other nine Timaliidae species, found that the species belong to the same Passeriformes all cluster together. PMID- 26678551 TI - Differences in the Clinical Outcome of Osteomyelitis by Treating Specialty: Orthopedics or Infectology. AB - Osteomyelitis is a heterogeneous infection with regard to etiology and treatment, and currently no single management protocol exists. Management of the condition is typically an interdisciplinary approach between orthopedics and infectious disease; however, the orthopedist is often the person who manages treatment. The aim of the study was to determine differences in the outcome of osteomyelitis according to its treating specialty and to identify factors associated with the recurrence of the disease. An ambispective cohort study of 129 patients with osteomyelitis was conducted and the proportions for qualitative variables and central tendency and dispersion measures for quantitative variables were calculated; the latter were tested for normality using the Shapiro-Wilk test. A bivariate analysis was conducted with measures of association based on the chi square test and crude relative risk. A logistic regression model was applied and statistical significance was set at p < 0.05, including the model of relevant clinical variables that fit the Hosmer-Lemeshow test. We found that 70% of patients were treated either by orthopedics or infectious disease. Patients who were treated by an orthopedist alone presented a greater risk of relapse or reinfection (RR = 4.6; 95% CI 2.3;8.9). Risk factors of osteomyelitis recurrence as determined in the regression model included the following: age of 57 years or older (RR = 1.3; 95% 0.3;5.2), long bones (RR = 1.9; 95% CI 0.5;7.1), fracture (RR = 5.0; 95% CI 0.4;51.4), monotherapy (RR = 3.0; 95% CI 0.6;14.5), receiving less than 4 weeks of antibiotics (RR = 1.5; 95% CI 0.2;10.1), inadequate treatment (RR = 3.1; 95% CI 0.4;20.1), and receiving orthopedics treatment (RR = 5.5; 95% CI 1.6;18.2). Most patients evaluated jointly by orthopedics and infectious disease received adequate treatment for osteomyelitis and had fewer relapses. PMID- 26678552 TI - Copper(II) Coordination Polymers Self-Assembled from Aminoalcohols and Pyromellitic Acid: Highly Active Precatalysts for the Mild Water-Promoted Oxidation of Alkanes. AB - Three novel water-soluble 2D copper(II) coordination polymers-[{Cu2(MU2 dmea)2(H2O)}2(MU4-pma)]n.4nH2O (1), [{Cu2(MU2-Hedea)2}2(MU4-pma)]n.4nH2O (2), and [{Cu(bea)(Hbea)}4(MU4-pma)]n.2nH2O (3)-were generated by an aqueous medium self assembly method from copper(II) nitrate, pyromellitic acid (H4pma), and different aminoalcohols [N,N-dimethylethanolamine (Hdmea), N-ethyldiethanolamine (H2edea), and N-benzylethanolamine (Hbea)]. Compounds 2 and 3 represent the first coordination polymers derived from H2edea and Hbea. All the products were characterized by infrared (IR), electron paramagnetic resonance (EPR), and ultraviolet-visible light (UV-vis) spectroscopy, electrospray ionization-mass spectroscopy (ESI-MS(+/-)), thermogravimetric and elemental analysis, and single crystal X-ray diffraction (XRD), which revealed that their two-dimensional (2D) metal-organic networks are composed of distinct dicopper(II) or monocopper(II) aminoalcoholate units and MU4-pyromellitate spacers. From the topological viewpoint, the underlying 2D nets of 1-3 can be classified as uninodal 4 connected layers with the sql topology. The structures of 1 and 2 are further extended by multiple intermolecular hydrogen bonds, resulting in three dimensional (3D) hydrogen-bonded networks with rare or unique topologies. The obtained compounds also act as highly efficient precatalysts for the mild homogeneous oxidation, by aqueous H2O2 in acidic MeCN/H2O medium, of various cycloalkanes to the corresponding alcohols and ketones. Overall product yields up to 45% (based on cycloalkane) were attained and the effects of various reaction parameters were investigated, including the type of precatalyst and acid promoter, influence of water, and substrate scope. Although water usually strongly inhibits the alkane oxidations, a very pronounced promoting behavior of H2O was detected when using the precatalyst 1, resulting in a 15-fold growth of an initial reaction rate in the cyclohexane oxidation on increasing the amount of H2O from ~4 M to 17 M in the reaction mixture, followed by a 2-fold product yield growth. PMID- 26678553 TI - 2015 Annual Meeting of the American Society for Bone and Mineral Research Seattle, WA October 9-12, 2015 (page S1). AB - Searchable abstracts may be found at http://www.asbmr.org/education/abstracts. PMID- 26678554 TI - Characterization of the Escherichia coli YajL, YhbO and ElbB glyoxalases. AB - The DJ-1 superfamily is a group of proteins that shares a similarity with the human DJ-1, known to be associated with Parkinson disease. Novel glyoxalase activity, converting alpha-oxoaldehydes to carboxylic acids, has been reported for DJ-1 homologs in humans, worms, plants and bacteria. The four Escherichia coli genes, hchA, yajL, yhbO and elbB, have been known to share sequence similarities and catalytic residues with other DJ-1 superfamily members. We investigated here whether they exhibit similar glyoxalase activity, as previously shown for HchA protein. Purified YajL, YhbO and ElbB exhibited glyoxalase activity with different substrate specificities, optimal pHs and metal effects. Overexpressions of the homologs enhance cellular protection from exogenously added glyoxals and reduce the glyoxal-dependent increase in intracellular advanced glycation end products. Based on their expression, primarily during the stationary phase, we speculate that their roles in cells as glyoxalases are manifested during the stationary phase. PMID- 26678555 TI - Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework. AB - Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past. PMID- 26678557 TI - [In Process Citation]. AB - Due to the anatomical proximity between the maxillary sinus and the teeth of the upper jaw, dislocation of tooth fragments or entire teeth into the sinus may occur during tooth extraction. Following the verification of such a foreign body within the sinus, its removal and the coverage of the oro-antral communication should be performed immediately for the prevention of possible sinus infection. In 2D-radiographic imaging, foreign bodies may not be located in the proper radiographic planes of an OPT or may be superimposed by other structures, complicating precise diagnosis. In such cases, 3D-imaging by CBCT is helpful. The present case report describes a female patient, being referred at our clinic for radiographic imaging and consecutive operative removal of a radix being dislocated into the right maxillary sinus. This radix relicta could be visualized by 3D-CBCT imaging. Consecutively, it was removed. PMID- 26678556 TI - I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing alpha5beta1 integrin signaling. AB - Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I-branching N acetylglucosaminyltransferase (GCNT2) converts linear i-antigen to I-branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin-embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2-positive cells were significantly lesser in organ-confined disease than in that with extra-capsular extensions, and GCNT2-negative tumors were associated with significantly better prostate-specific antigen-free survival compared with GCNT2-positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I-antigen on the O-glycan and glycolipid. Moreover, I antigen-bearing glycolipids were subject to alpha5beta1 integrin-fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa. PMID- 26678558 TI - The development of the modified blaylock tool for occupational therapy referral (MBTOTR): a preliminary evaluation of its utility in acute care. AB - PURPOSE: Acute hospitals are facing more complex admissions with older people at increased risk of functional decline. This study aimed to create and trial the feasibility of a new screening tool designed to identify patients at risk of functional decline who need an occupational therapy referral within acute care. METHOD: Ten screening tools were reviewed and the Modified Blaylock Tool for Occupational Therapy Referral (MBTOTR) was developed. The MBTOTR was applied in a retrospective chart review of 50 patients over the age of 65 years who were admitted to five acute wards. Data on patients identified at risk of functional decline were compared to patients who were referred to occupational therapy. RESULTS: Occupational therapy referrals were made by ward staff for 14 out of the 50 patients reviewed (32.5%). Only 14% (n = 7) of patients did not require a referral. The MBTOTR identified no irrelevant occupational therapy referrals. However, 66.5% of patients identified as needing an occupational therapy referral did not get one. CONCLUSION: The MBTOTR identified high risk acute patients requiring an occupational therapy referral who were not referred to occupational therapy. Use of the MBTOTR would facilitate early occupational therapy referrals for complex patients, and potentially better discharge outcomes. Implications for rehabilitation The MBTOTR can be used in acute care settings to facilitate relevant occupational therapy referrals. Without a screening tool, many older people who should have an occupational therapy assessment may not receive a referral for occupational therapy. Nursing and medical staff need to use this tool to identify older people in their care who may benefit from occupational therapy assessment and intervention. If occupational therapy referrals can be made early, this may contribute to reducing delays to discharge plans for complex patients. PMID- 26678559 TI - Interstitial pneumonia during administration of dipeptidyl peptidase-4 inhibitors. PMID- 26678560 TI - Thiolated Au18 cluster: preferred Ag sites for doping, structures, and optical and chiroptical properties. AB - Recently, the X-ray determined structure of the thiolated Au18 cluster has been reported. In this communication, we addressed a study of structures and chiroptical properties of thiolated Au18 cluster doped with up to ten Ag atoms, which have been calculated by Time Dependent Density Functional Theory (TD-DFT). The number of Ag atoms was steadily varied and more stable isomers showed optical and Circular Dichroism (CD) spectra distinct from that found for the parent Au18 cluster. Doping with more than four Ag atoms results in enhancement of the oscillator strength of the HOMO-LUMO peak and it is expected that this feature can be exploited for photoluminescence applications. PMID- 26678561 TI - Correction: Molecular Characterization of Circulating Respiratory Syncytial Virus (RSV) Genotypes in Gilgit Baltistan Province of Pakistan during 2011-2012 Winter Season. PMID- 26678562 TI - Surgical trends in the correction of female stress urinary incontinence in academic centers within the United States. AB - AIMS: There is a lack of data describing the current state of stress urinary incontinence (SUI) procedures in academic centers. Urologists, gynecologists, and urogynecologists perform these operations, but the relative volume each group accounts for is unknown. The purpose of this study was to evaluate the distribution of cases in academic centers between specialties and associated patient characteristics. METHODS: A hospital consortium database was used to identify patients treated surgically for SUI between 2009 and 2014. Patient and surgeon variables were evaluated. Patient variables (age, region, insurance, race) and surgeon volume were analyzed. Sub-analysis was conducted to determine concomitant prolapse repairs. RESULTS: Of the 50,315 stress urinary incontinence procedures performed, 22% were performed by urologists. Overall volume dropped 39% and mean surgeon volumes for all three groups decreased with time. Average median volume for urogynecologists (29/year) differed from both urologists (3/year) and non-urogynecologists (2/year). There was a significant difference in rate of concomitant prolapse repairs performed by urogynecologists (56%), gynecologists (54%), and urologists (26%). CONCLUSIONS: These data portray the changing pattern of SUI procedure practice in academic centers. Academic urologists are performing less than 25% of SUI procedures, with an overall decline in number of procedures across all specialties. Urogynecologists and gynecologists are performing a significantly higher proportion of concomitant prolapse repairs. Neurourol. Urodynam. 36:394-398, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26678563 TI - Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. AB - Osteopontin (OPN) is a multifunctional integrin-binding protein present in several tissues and body fluids. OPN is a substrate for the enzyme transglutaminase 2 (TG2), which catalyzes inter- and intramolecular cross-linking affecting the biological activity of the protein. Polymerization of OPN by intermolecular cross-linking has mostly been studied using relatively high TG2 concentrations, whereas the effect of lower concentrations of TG2 has remained unexplored. Here we show that TG2 at physiologically relevant concentrations predominantly catalyzes the formation of intramolecular cross-links in OPN. By site-directed mutagenesis and mass spectrometry, we demonstrate that Gln(42) and Gln(193) serve as the primary amine acceptor sites for isopeptide bond formation. We find that Gln(42) predominantly is linked to Lys(4) and that Gln(193) participates in a cross-link with Lys(154), Lys(157), or Lys(231). The formation of specific isopeptide bonds was not dependent on OPN phosphorylation, and similar patterns of cross-linking were observed in human and mouse OPN. Furthermore, we find that OPN purified from human urine contains the Lys(154) Gln(193) isopeptide bond, indicating that intramolecular cross-linking of OPN occurs in vivo. Collectively, these data suggest that specific intramolecular cross-linking in the N- and C-terminal parts of OPN is most likely the dominant step in TG2-catalyzed modification of OPN. PMID- 26678564 TI - Applying the welfare model to at-own-risk discharges. AB - "At-own-risk discharges" or "self-discharges" evidences an irretrievable breakdown in the patient-clinician relationship when patients leave care facilities before completion of medical treatment and against medical advice. Dissolution of the therapeutic relationship terminates the physician's duty of care and professional liability with respect to care of the patient. Acquiescence of an at-own-risk discharge by the clinician is seen as respecting patient autonomy. The validity of such requests pivot on the assumptions that the patient is fully informed and competent to invoke an at-own-risk discharge and that care up to the point of the at-own-risk discharge meets prevailing clinical standards. Palliative care's use of a multidisciplinary team approach challenges both these assumptions. First by establishing multiple independent therapeutic relations between professionals in the multidisciplinary team and the patient who persists despite an at-own-risk discharge. These enduring therapeutic relationships negate the suggestion that no duty of care is owed the patient. Second, the continued employ of collusion, familial determinations, and the circumnavigation of direct patient involvement in family-centric societies compromises the patient's decision-making capacity and raises questions as to the patient's decision-making capacity and their ability to assume responsibility for the repercussions of invoking an at-own-risk discharge. With the validity of at-own-risk discharge request in question and the welfare and patient interest at stake, an alternative approach to assessing at-own-risk discharge requests are called for. The welfare model circumnavigates these concerns and preserves the patient's welfare through the employ of a multidisciplinary team guided holistic appraisal of the patient's specific situation that is informed by clinical and institutional standards and evidenced-based practice. The welfare model provides a robust decision-making framework for assessing the validity of at-own-risk discharge requests on a case by-case basis. PMID- 26678565 TI - High-temperature superconductivity from fine-tuning of Fermi-surface singularities in iron oxypnictides. AB - In the family of the iron-based superconductors, the REFeAsO-type compounds (with RE being a rare-earth metal) exhibit the highest bulk superconducting transition temperatures (Tc) up to 55 K and thus hold the key to the elusive pairing mechanism. Recently, it has been demonstrated that the intrinsic electronic structure of SmFe0.92Co0.08AsO (Tc = 18 K) is highly nontrivial and consists of multiple band-edge singularities in close proximity to the Fermi level. However, it remains unclear whether these singularities are generic to the REFeAsO-type materials and if so, whether their exact topology is responsible for the aforementioned record Tc. In this work, we use angle-resolved photoemission spectroscopy (ARPES) to investigate the inherent electronic structure of the NdFeAsO0.6F0.4 compound with a twice higher Tc = 38 K. We find a similarly singular Fermi surface and further demonstrate that the dramatic enhancement of superconductivity in this compound correlates closely with the fine-tuning of one of the band-edge singularities to within a fraction of the superconducting energy gap Delta below the Fermi level. Our results provide compelling evidence that the band-structure singularities near the Fermi level in the iron-based superconductors must be explicitly accounted for in any attempt to understand the mechanism of superconducting pairing in these materials. PMID- 26678566 TI - YAGM: a web tool for mining associated genes in yeast based on diverse biological associations. AB - BACKGROUND: Investigating association between genes can be used in understanding the relations of genes in biological processes. STRING and GeneMANIA are two well known web tools which can provide a list of associated genes of a query gene based on diverse biological associations such as co-expression, co-localization, co-citation and so on. However, the transcriptional regulation association and mutant phenotype association have not been used in these two web tools. Since the comprehensive transcription factor (TF)-gene binding data, TF-gene regulation data and mutant phenotype data are available in yeast, we developed a web tool called YAGM (Yeast Associated Genes Miner) which constructed the transcriptional regulation association, mutant phenotype association and five commonly used biological associations to mine a list of associated genes of a query yeast gene. DESCRIPTION: In YAGM, we collected seven kinds of datasets including TF-gene binding (TFB) data, TF-gene regulation (TFR) data, mutant phenotype (MP) data, functional annotation (FA) data, physical interaction (PI) data, genetic interaction (GI) data, and literature evidence (LE) data. Then by using the hypergeometric test to calculate the association scores of all gene pairs in yeast, we constructed seven biological associations including two transcriptional regulation associations (TFB association and TFR association), MP association, FA association, PI association, GI association, and LE association. Moreover, the expression profile association from SPELL database was also included in YAGM. When using YAGM, users can input a query gene and choose any possible subsets of the eight biological associations, then a list of associated genes of the query gene will be returned based on the chosen biological associations. CONCLUSIONS: In this study, we presented the YAGM which provides eight biological associations for mining associated genes of a query gene in yeast. Among the eight biological associations constructed in YAGM, three (TFB association, TFR association, and MP association) are novel ones. By comparing the query results of two well-known web tools (STRING and GeneMANIA), we found that YAGM can find out distinct associated genes of a query gene. That is, YAGM can provide alternative candidates of associated genes for biologists to do further experimental investigation. We believe that YAGM will be a useful web tool for yeast biologists. YAGM is available online at http://cosbi3.ee.ncku.edu.tw/yagm/. PMID- 26678567 TI - Exposure to violence predicts poor educational outcomes in young children in South Africa and Malawi. AB - BACKGROUND: Violence during childhood may affect short and long-term educational factors. There is scant literature on younger children from resource poor settings. METHODS: This study assessed child violence experiences (harsh punishment and exposure to domestic or community violence) and school enrolment, progress and attendance in children attending community-based organisations in South Africa and Malawi (n=989) at baseline and at 15 months' follow-up, examining differential experience of HIV positive, HIV affected and HIV unaffected children. RESULTS: Violence exposure was high: 45.4% experienced some form of psychological violence, 47.8% physical violence, 46.7% domestic violence and 41.8% community violence. Primary school enrolment was 96%. Violence was not associated with school enrolment at baseline but, controlling for baseline, children exposed to psychological violence for discipline were more than ten times less likely to be enrolled at follow-up (OR 0.09; 95% CI 0.01 to 0.57). Harsh discipline was associated with poor school progress. For children HIV positive a detrimental effect of harsh physical discipline was found on school performance (OR 0.10; 95% CI 0.02 to 0.61). CONCLUSION: Violence experiences were associated with a number of educational outcomes, which may have long-term consequences. Community-based organisations may be well placed to address such violence, with a particular emphasis on the challenges faced by children who are HIV positive. PMID- 26678568 TI - Behavioural and emotional responses to the 2014 Ebola outbreak in Nigeria: a narrative review. AB - This paper reviews the behavioural and emotional responses to the 2014 Ebola virus disease (EVD) outbreak in Nigeria as documented in scientific publications and portrayed in the media between 21 July 2014 and 30 March 2015. The outbreak generated national interest and there were reports of patients suspected of having Ebola being avoided for fear of contracting the disease, misconceptions about EVD prevention and protests against locations of EVD-treatment centres. Suspected and confirmed EVD patients, as well as healthcare workers (HCW) who treated them, faced stigma and discrimination. The federal and state governments, and their local and international partners, responded promptly with a robust and coordinated prevention and control strategy that included regular dissemination of accurate information and social mobilisation, among others. Although general apprehension about EVD was reported among HCWs in Nigeria, many HCWs eventually volunteered to manage confirmed cases, to trace contacts and to participate in the country's control effort. Local anthropological studies are necessary to determine drivers of social responses to the EVD outbreak in Nigeria. PMID- 26678569 TI - The Most Popular Smartphone Apps for Weight Loss: A Quality Assessment. AB - BACKGROUND: Advancements in mobile phone technology have led to the development of smartphones with the capability to run apps. The availability of a plethora of health- and fitness-related smartphone apps has the potential, both on a clinical and public health level, to facilitate healthy behavior change and weight management. However, current top-rated apps in this area have not been extensively evaluated in terms of scientific quality and behavioral theory evidence base. OBJECTIVE: The purpose of this study was to evaluate the quality of the most popular dietary weight-loss smartphone apps on the commercial market using comprehensive quality assessment criteria, and to quantify the behavior change techniques (BCTs) incorporated. METHODS: The top 200-rated Health & Fitness category apps from the free and paid sections of Google Play and iTunes App Store in Australia (n=800) were screened in August 2014. To be included in further analysis, an app had to focus on weight management, include a facility to record diet intake (self-monitoring), and be in English. One researcher downloaded and used the eligible apps thoroughly for 5 days and assessed the apps against quality assessment criteria which included the following domains: accountability, scientific coverage and content accuracy of information relevant to weight management, technology-enhanced features, usability, and incorporation of BCTs. For inter-rater reliability purposes, a second assessor provided ratings on 30% of the apps. The accuracy of app energy intake calculations was further investigated by comparison with results from a 3-day weighed food record (WFR). RESULTS: Across the eligible apps reviewed (n=28), only 1 app (4%) received full marks for accountability. Overall, apps included an average of 5.1 (SD 2.3) out of 14 technology-enhanced features, and received a mean score of 13.5 (SD 3.7) out of 20 for usability. The majority of apps provided estimated energy requirements (24/28, 86%) and used a food database to calculate energy intake (21/28, 75%). When compared against the WFR, the mean absolute energy difference of apps which featured energy intake calculations (23/28, 82%) was 127 kJ (95% CI -45 to 299). An average of 6.3 (SD 3.7) of 26 BCTs were included. CONCLUSIONS: Overall, the most popular commercial apps for weight management are suboptimal in quality, given the inadequate scientific coverage and accuracy of weight-related information, and the relative absence of BCTs across the apps reviewed. With the limited regulatory oversight around the quality of these types of apps, this evaluation provides clinicians and consumers an informed view of the highest quality apps in the current popular app pool appropriate for recommendation and uptake. Further research is necessary to assess the effectiveness of apps for weight management. PMID- 26678570 TI - Microglia modulate respiratory rhythm generation and autoresuscitation. AB - Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBotzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation. PMID- 26678572 TI - Pharmacogenetics of multiple sclerosis: personalized therapy with immunomodulatory drugs. AB - Pharmacogenetic (PG) studies aim to discover the individual genetic background that underlies the heterogeneity of treatment response, and thus find biomarkers for identification of individual patients who will benefit the most from the therapy administered or urgently require the alternate drug. Over the last decade, PG studies have made progress in terms of multiple sclerosis (MS), which is one of the most severe neurodegenerative diseases of the central nervous system. With the understanding of the role of the immune system in the pathogenesis of MS, a number of immunomodulatory drugs were developed for MS treatment management. However, clinical response to these disease-modifying therapies varies in individual patients. Interferon-beta and glatiramer acetate showed the most reliable long-term safety and remain among the first-line disease modifying therapies for MS worldwide. Here, we will review the results of interferon-beta and glatiramer acetate PG studies with a detailed analysis of study design and approaches, their advantages and limitations, and future perspectives. PMID- 26678573 TI - Differential introgression and reorganization of retrotransposons in hybrid zones between wild wheats. AB - The maintenance of species integrity despite pervasive hybridization is ruled by the interplay between reproductive barriers. Endogenous postzygotic isolation will shape the patterns of introgression in hybrid zones, leading to variable outcomes depending on the genetic mechanism involved. Here, we analysed experimental and natural hybrid populations of Aegilops geniculata and Aegilops triuncialis to examine the genetics of species boundaries in the face of gene flow. Because long-terminal repeat retrotransposons (LTR-RTs) showing differential evolutionary trajectories are probably to affect hybrid dysgenesis and reproductive isolation between these wild wheat species, we addressed the impact of LTR-RTs in shaping introgression between them. Experimental settings involving artificial sympatry and enforced crossings quantified strong, but incomplete reproductive isolation, and highlighted asymmetrical endogenous postzygotic isolation between the two species. Natural hybrid zones located in the northern Golan Heights were analysed using plastid DNA, amplified fragment length polymorphisms (AFLP) marking random sequences, and sequence-specific amplified polymorphisms (SSAP) tracking insertions from six LTR-RT families. This analysis demonstrated asymmetrical introgression and genome reorganization. In comparison with random sequences and quiescent LTR-RTs, those LTR-RTs predicted to be activated following conflicting interactions in hybrids revealed differential introgression across the hybrid zones. As also reported for synthetic F1 hybrids, such LTR-RTs were specifically reorganized in the genomes of viable hybrids, confirming that conflicts between selfish LTR-RTs may represent key incompatibilities shaping species boundaries and fostering long term species integrity in the face of gene flow. PMID- 26678574 TI - Spatial resolution effect of light coupling structures. AB - The coupling of light between free space and thin film semiconductors is an essential requirement of modern optoelectronic technology. For monochromatic and single mode devices, high performance grating couplers have been developed that are well understood. For broadband and multimode devices, however, more complex structures, here referred to as "coupling surfaces", are required, which are often difficult to realise technologically. We identify general design rules based on the Fourier properties of the coupling surface and show how they can be used to determine the spatial resolution required for the coupler's fabrication. To our knowledge, this question has not been previously addressed, but it is important for the understanding of diffractive nanostructures and their technological realisation. We exemplify our insights with solar cells and UV photodetectors, where high-performance nanostructures that can be realised cost effectively are essential. PMID- 26678594 TI - Self-assembled honeycomb lattice in the monolayer of cyclic thiazyl diradical BDTDA (= 4,4'-bis(1,2,3,5-dithiadiazolyl)) on Cu(111) with a zero-bias tunneling spectra anomaly. AB - Scanning tunneling microscopy (STM) observation reveals that a cyclic thiazyl diradical, BDTDA (= 4,4'-bis(1,2,3,5-dithiadiazolyl)), forms a well-ordered monolayer honeycomb lattice consisting of paramagnetic corners with unpaired electrons on a clean Cu(111) surface. This BDTDA lattice is commensurate with the triangular lattice of Cu(111), with the former being 3 * 3 larger than the latter. The formation of the BDTDA monolayer structure, which is significantly different from its bulk form, is attributed to an interaction with the metal surface as well as the intermolecular assembling forces. STM spectroscopy measurements on the BDTDA molecules indicate the presence of a characteristic zero-bias anomaly centered at the Fermi energy. The origin of this zero-bias anomaly is discussed in terms of the Dirac cones inherent to the honeycomb structure. PMID- 26678595 TI - Magnetically modulated critical current densities of Co/Nb hybrid. AB - By tuning morphology and size of magnetic subsystem, ferromagnet-superconductor (F/S) hybrid system provides an effective way to modulate superconductivity due to the interaction between superconducting and magnetic-order parameters at the mesoscopic length scale. In this work, we report on investigations of critical current density in a large-area Co/Nb hybrid via facile colloidal lithography. Here, Co hexagon shell array as a magnetic template build on Nb film to modulate the critical current density. A novel superconducting transition has been observed in I-V curve with two metastable transition states: double-transition and binary-oscillation-transition states. Importantly, such unusual behavior can be adjusted by temperature, magnetic field and contact area of F/S. Such hybrid film has important implications for understanding the role of magnetic subsystem modulating superconductivity, as well as applied to low-energy electronic devices such as superconducting current fault limiters. PMID- 26678593 TI - Childhood abdominal tuberculosis: Disease patterns, diagnosis, and drug resistance. AB - OBJECTIVE: Childhood abdominal tuberculosis may be difficult to diagnose with certainty. Drug resistance adds to the challenge. We present our experience in children with this condition. METHODS: The case records of all children <18 years of age and diagnosed as abdominal tuberculosis from January 2000 to April 2012 were reviewed. The clinical details; investigative profile (imaging, ascitic fluid analysis, upper gastrointestinal (GI) endoscopy, colonoscopy, and laparotomy); histopathology; microbiology; and response to antitubercular therapy was noted. RESULTS: Thirty-eight children (median age 11, range 4-16 years) were diagnosed. Multiple intraabdominal sites were involved in 12 (32 %), peritoneal alone in 9 (24 %); isolated intestinal and isolated lymph nodal in 6 (16 %) each. Three children had atypical presentations with gastric outlet obstruction, acute lower GI bleeding, and duodenal perforation, respectively. Overall, definitive bacteriological diagnosis was possible in 47 % (18/38). In others, diagnosis was supported by histopathology (19 %) or other supportive investigations (34 %) along with a response to treatment without relapse. Drug-resistant disease was diagnosed in three (8 %, two multidrug resistant, one extended drug resistant) all of whom presented with a similar clinical picture of large abdominal lymph node masses. CONCLUSION: Abdominal tuberculosis is still a challenging diagnosis with microbiological confirmation possible only in half of the cases. Atypical presentations and emergence of drug resistance should be kept in mind while managing these patients. PMID- 26678597 TI - Modeling error in experimental assays using the bootstrap principle: understanding discrepancies between assays using different dispensing technologies. AB - All experimental assay data contains error, but the magnitude, type, and primary origin of this error is often not obvious. Here, we describe a simple set of assay modeling techniques based on the bootstrap principle that allow sources of error and bias to be simulated and propagated into assay results. We demonstrate how deceptively simple operations--such as the creation of a dilution series with a robotic liquid handler--can significantly amplify imprecision and even contribute substantially to bias. To illustrate these techniques, we review an example of how the choice of dispensing technology can impact assay measurements, and show how large contributions to discrepancies between assays can be easily understood and potentially corrected for. These simple modeling techniques- illustrated with an accompanying IPython notebook--can allow modelers to understand the expected error and bias in experimental datasets, and even help experimentalists design assays to more effectively reach accuracy and imprecision goals. PMID- 26678598 TI - Notes from the Field: Acute Mercury Poisoning After Home Gold and Silver Smelting -Iowa, 2014. AB - In March 2014, a man, aged 59 years, who lived alone and had been using different smelting techniques viewed on the Internet to recover gold and silver from computer components, was evaluated at a local emergency department for shortness of breath, tremors, anorexia, and generalized weakness. During the smelting processes, he had used hydrogen peroxide, nitric acid, muriatic acid, and sulfuric acid purchased from local stores or Internet retailers. For protection, he wore a military gas mask of unknown type. The mask was used with filter cartridges, but their effectiveness against chemical fumes was not known. PMID- 26678596 TI - Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures. AB - The lateral and third ventricles, as well as the corpus callosum (CC), are known to be affected in schizophrenia. Here we investigate whether abnormalities in the lateral ventricles (LVs), third ventricle, and corpus callosum are related to one another in first episode schizophrenia (FESZ), and whether such abnormalities show progression over time. Nineteen FESZ and 19 age- and handedness-matched controls were included in the study. MR images were acquired on a 3-Tesla MRI at baseline and ~1.2 years later. FreeSurfer v.5.3 was employed for segmentation. Two-way or univariate ANCOVAs were used for statistical analysis, where the covariate was intracranial volume. Group and gender were included as between subjects factors. Percent volume changes between baseline and follow-up were used to determine volume changes at follow-up. Bilateral LV and third ventricle volumes were significantly increased, while central CC volume was significantly decreased in patients compared to controls at baseline and at follow-up. In FESZ, the bilateral LV volume was also inversely correlated with volume of the central CC. This inverse correlation was not present in controls. In FESZ, an inverse correlation was found between percent volume increase from baseline to follow-up for bilateral LVs and lesser improvement in the Global Assessment of Functioning score. Significant correlations were observed for abnormalities of central CC, LVs and third ventricle volumes in FESZ, suggesting a common neurodevelopmental origin in schizophrenia. Enlargement of ventricles was associated with less improvement in global functioning over time. PMID- 26678599 TI - Dose-volume relationships for moderate or severe neck muscle atrophy after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. AB - This study aimed to identify the dosimetric parameters and radiation dose tolerances associated with moderate or severe sternocleidomastoid muscle (SCM) atrophy after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). We retrospectively analysed 138 patients treated with IMRT between 2011 and 2012 for whom IMRT treatment plans and pretreatment and 3-year post-IMRT MRI scans were available. The association between mean dose (Dmean), maximum dose (Dmax), VX (% SCM volume that received more than X Gy), DX (dose to X% of the SCM volume) at X values of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 and SCM atrophy at 3 years after IMRT were analyzed. All dosimetric parameters, except V40, V50 and V80, were significantly associated with moderate or severe SCM atrophy. Multivariate analysis showed that V65 was an independent predictor of moderate or severe SCM atrophy (P < 0.001). Receiver operating characteristic (ROC) curve indicated a V65 of 21.47% (area under ROC curves, 0.732; P < 0.001) was the tolerated dose for moderate or severe SCM atrophy. We suggest a limit of 21.47% for V65 to optimize NPC treatment planning, whilst minimizing the risk of moderate or severe SCM atrophy. PMID- 26678600 TI - Suppression of vascular network formation by chronic hypoxia and prolyl hydroxylase 2 (phd2) deficiency during vertebrate development. AB - In the adult, new vessels and red blood cells form in response to hypoxia. Here, the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are considered as potential therapeutic targets to treat ischemia, cancers or age related macula degeneration. While the oxygen-sensing system (PHD-HIF) has been studied intensively in this respect, only little is known from developing vertebrate embryos since mutations within this pathway led to an early decease of embryos due to placental defects. During vertebrate embryogenesis, a progenitor cell called hemangioblast is assumed to give rise to blood cells and blood vessels in a process called hematopoiesis and vasculogenesis, respectively. Xenopus provides an ideal experimental system to address these processes in vivo, as its development does not depend on a functional placenta and thus allows analyzing the role of oxygen directly. To this end, we adopted a computer controlled four-channel system, which allowed us to culture Xenopus embryos under defined oxygen concentrations. Our data show that the development of vascular structures and blood cells is strongly impaired under hypoxia, while general development is less compromised. Interestingly, suppression of Phd2 function using specific antisense morpholinos or a chemical inhibitor resulted in mostly overlapping vascular defects; nevertheless, blood cell was formed almost normally. Our results provide the first evidence that oxygen via Phd2 has a decisive influence on the formation of the vascular network during vertebrate embryogenesis. These findings may be considered in certain potential treatment concepts. PMID- 26678601 TI - Targeting the Hippo pathway: Clinical implications and therapeutics. AB - The Hippo pathway plays a critical role in tissue and organ size regulation by restraining cell proliferation and apoptosis under homeostatic conditions. Deregulation of this pathway can promote tumorigenesis in multiple malignant human tumor types, including sarcoma, breast, lung and liver cancers. In this review, we summarize the current understanding of Hippo pathway function, it's role in human cancer, and address the potential of Hippo pathway member proteins as therapeutic targets for a variety of tumors. PMID- 26678602 TI - Targeting VEGF in eye neovascularization: What's new?: A comprehensive review on current therapies and oligonucleotide-based interventions under development. AB - Roughly ten years ago the FDA approved most of the presently used anti-VEGF drugs for the treatment of neovascular AMD and other eye pathologies characterized by ocular neoangiogenesis. However, the recent findings on the physiologic activities of VEGF isoforms impose to reconsider the inhibitory effects of pan VEGF antagonists and the concept that to face pathological alterations at ocular level is possible only through the full block of all VEGF isoforms. In fact, although pan-VEGF agents rapidly and effectively contrast ocular neovascularization, vascular leakage, and other pathological changes, in the long term the inhibition of all VEGF isoforms likely may result in the loss of the physiologic effects exerted by VEGF121 and the anti-angiogenic VEGF165b. Notably, selective inhibitors of VEGF165a, such as pegaptanib, spare these targets. Moreover, preclinical and clinical evidence suggests that also systemic side effects, secondary to intraocular treatment with non-selective anti-VEGF drugs, may be reinterpreted in light of these recent findings, which may be useful to clinicians for the choice of the most appropriate anti-VEGF agent. Another aspect that should be considered is the involvement of VEGF-independent pathways in ocular neovascularization, therefore a combined therapy can represent a more effective pharmacological approach that might help also to counteract tachyphylaxis, an important issue in anti-VEGF treatment. This complex picture and the recent findings on current anti-VEGF drugs should be therefore taken into account to guide the development of novel agents targeting VEGF and/or other key factors involved in the pathogenesis of neovascular ocular diseases along the signaling pathways stimulated by the various isoforms. Accordingly, this review also reports on novel pharmacological molecules targeting VEGF at ocular level and currently under development, with a special attention to oligonucleotide based interventions. PMID- 26678603 TI - Birth weight, intrauterine growth restriction and nutritional status in childhood in relation to grip strength in adults: from the 1982 Pelotas (Brazil) birth cohort. AB - OBJECTIVE: The aim of this study was to evaluate the association among birth weight, intrauterine growth, and nutritional status in childhood with grip strength in young adults from the 1982 Pelotas (Brazil) birth cohort. METHODS: In 1982, the hospital live births of Pelotas were followed. In 2012, grip strength was evaluated using a hand dynamometer and the best of the six measurements was used. Birth weight was analyzed as z-score for gestational age according to Williams (1982) curve. Weight-for-age, weight-for-length/height, and length/height-for-age at 2 and 4 y were analyzed in z-scores according to 2006 World Health Organization Child Growth Standards. Lean mass at 30 y was included as possible mediator using the g-computation formula. RESULTS: In 2012, 3701 (68.1%) individuals were interviewed and 3470 were included in the present analyses. An increase of 1 z-score in birth weight was associated with an increase of 1.5 kg in grip strength in males (95% confidence interval, 1.1-1.9). Positive effect of birth weight on grip strength was found in females. Grip strength was greater in individuals who were born with appropriate size for gestational age and positively associated with weight- and length/height-for-age z-score at 2 and 4 y of age. A positive association between birth weight and grip strength was only partially mediated by adult lean mass (50% and 33% of total effect in males and females), whereas direct effect of weight at 2 y was found only in males. CONCLUSIONS: It is suggested that good nutrition in prenatal and early postnatal life has a positive influence on adult muscle strength. The results from birth weight were suggestive of fetal programming on grip strength measurement. PMID- 26678608 TI - Protein Design: Getting to the bottom of the TIM barrel. PMID- 26678609 TI - Probe discovery: Disentangling gene networks. PMID- 26678610 TI - Transcriptional kinases: Less is more (or less). PMID- 26678611 TI - Interactive Sensor-Based Balance Training in Older Cancer Patients with Chemotherapy-Induced Peripheral Neuropathy: A Randomized Controlled Trial. AB - BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) have deficits in sensory and motor skills leading to inappropriate proprioceptive feedback, impaired postural control, and fall risk. Balance training programs specifically developed for CIPN patients are lacking. OBJECTIVE: This pilot study investigated the effect of an interactive motor adaptation balance training program based on wearable sensors for improving balance in older cancer patients with CIPN. METHODS: Twenty-two patients (age: 70.3 +/- 8.7 years) with objectively confirmed CIPN [vibration perception threshold (VPT) >25 V] were randomized to either an intervention (IG) or a control (CG) group. The IG received interactive game-based balance training including repetitive weight shifting and virtual obstacle crossing tasks. Wearable sensors provided real-time visual/auditory feedback from the lower limb trajectory and allowed the perception of motor errors during each motor action. The CG received no exercise intervention and continued their normal activity. Outcome measures were changes in sway of ankle, hip, and center of mass (CoM) in both mediolateral and anteroposterior (AP) directions during 30-second balance tests with increasing task difficulty [i.e. standing in feet-closed position with eyes open (EO) and eyes closed (EC), and in semi-tandem position with EO] at baseline and after the intervention. Additionally, gait performance (speed, variability) and fear of falling [Falls Efficacy Scale-International (FES-I)] were measured. RESULTS: Training was safe despite the participants' impaired health status, great severity of CIPN (VPT 49.6 +/- 26.7 V), and great fear of falling (FES-I score 31.37 +/- 11.20). After the intervention, sway of hip, ankle, and CoM was significantly reduced in the IG compared to the CG while standing in feet-closed position with EO (p = 0.010-0.022, except AP CoM sway) and in semi-tandem position (p = 0.008-0.035, except ankle sway). No significant effects were found for balance with EC, gait speed, and FES-I score (p > 0.05). CONCLUSIONS: This proof-of-concept study demonstrates that older cancer patients with CIPN can significantly improve their postural balance with specifically tailored, sensor-based exercise training. The training approach has potential as a therapy for improving CIPN-related postural control deficits. However, future studies comparing the proposed technology-based training with traditional balance training are required to evaluate the benefit of the interactive joint movement feedback. PMID- 26678612 TI - Human Dermal Fibroblasts Demonstrate Positive Immunostaining for Neuron- and Glia Specific Proteins. AB - In stem cell cultures from adult human tissue, undesirable contamination with fibroblasts is frequently present. The presence of fibroblasts obscures the actual number of stem cells and may result in extracellular matrix production after transplantation. Identification of fibroblasts is difficult because of the lack of specific fibroblast markers. In our laboratory, we isolate and expand neural-crest-derived stem cells from human hair follicle bulges and investigate their potential to differentiate into neural cells. To establish cellular identities, we perform immunohistochemistry with antibodies specific for glial and neuronal markers, and use fibroblasts as negative control. We frequently observe that human adult dermal fibroblasts also express some glial and neuronal markers. In this study, we have sought to determine whether our observations represent actual expression of these markers or result from cross-reactivity. Immunohistochemistry was performed on human adult dermal fibroblasts using acknowledged glial and neuronal antibodies followed by verification of the data using RT-qPCR. Human adult dermal fibroblasts showed expression of the glia specific markers SOX9, glial fibrillary acidic protein and EGR2 (KROX20) as well as for the neuron-specific marker class III beta-tubulin, both at the protein and mRNA level. Furthermore, human adult dermal fibroblasts showed false-positive immunostaining for S100beta and GAP43 and to a lower extent for OCT6. Our results indicate that immunophenotyping as a tool to determine cellular identity is not as reliable as generally assumed, especially since human adult dermal fibroblasts may be mistaken for neural cells, indicating that the ultimate proof of glial or neuronal identity can only be provided by their functionality. PMID- 26678613 TI - Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. AB - Small and flat adenomas are known to carry a high miss-rate during standard white light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted near-infrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. METHODS: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples--48 sessile serrated adenomas/polyps, 70 sporadic high grade dysplastic adenomas, and 19 hyperplastic polyps--and tissue derived from patients with Lynch syndrome--78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116(luc) tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116(luc) tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. RESULTS: Immunohistochemistry showed high VEGF-A expression in 79%-96% and high EGFR expression in 51%-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. CONCLUSION: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field red-flag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach. PMID- 26678614 TI - 99mTc-Nanocolloid SPECT/MRI Fusion for the Selective Assessment of Nonenlarged Sentinel Lymph Nodes in Patients with Early-Stage Cervical Cancer. AB - We aimed to explore the accuracy of (99m)Tc SPECT/MRI fusion for the selective assessment of nonenlarged sentinel lymph nodes (SLNs) for diagnosing metastases in early-stage cervical cancer patients. METHODS: We consecutively included stage IA1-IIB1 cervical cancer patients who presented to our tertiary referral center between March 2011 and February 2015. Patients with enlarged lymph nodes (short axis >= 10 mm) on MRI were excluded. Patients underwent an SLN procedure with preoperative (99m)Tc-nanocolloid SPECT/CT-based SLN mapping. When fused datasets of the SPECT and MR images were created, SLNs could be identified on the MR image with accurate correlation to the histologic result of each individual SLN. An experienced radiologist, masked to histology, retrospectively reviewed all fused SPECT/MR images and scored morphologic SLN parameters on a standardized case report form. Logistic regression and receiver-operating curves were used to model the parameters against the SLN status. RESULTS: In 75 cases, 136 SLNs were eligible for analysis, of which 13 (9.6%) contained metastases (8 cases). Three parameters-short-axis diameter, long-axis diameter, and absence of sharp demarcation-significantly predicted metastatic invasion of nonenlarged SLNs, with quality-adjusted odds ratios of 1.42 (95% confidence interval [CI], 1.01-1.99), 1.28 (95% CI, 1.03-1.57), and 7.55 (95% CI, 1.09-52.28), respectively. The area under the curve of the receiver-operating curves combining these parameters was 0.749 (95% CI, 0.569-0.930). Heterogeneous gadolinium enhancement, cortical thickness, round shape, or SLN size, compared with the nearest non-SLN, showed no association with metastases (P= 0.055-0.795). CONCLUSION: In cervical cancer patients without enlarged lymph nodes, selective evaluation of only the SLNs-for size and absence of sharp demarcation-can be used to noninvasively assess the presence of metastases. PMID- 26678615 TI - Primary Tumor 18F-FDG Avidity Affects the Performance of 18F-FDG PET/CT for Detecting Gastric Cancer Recurrence. AB - The usefulness of (18)F-FDG PET in gastric cancer recurrence is limited by low sensitivity. Given that detectability by PET is dependent on the tumor's metabolic characteristics, we tested whether the performance of PET for gastric cancer recurrence is enhanced in patients with (18)F-FDG-avid primary tumors. METHODS: Three hundred sixty-eight patients with advanced gastric cancer underwent (18)F-FDG PET/CT for initial staging and for recurrence surveillance after curative surgery. On initial PET/CT, primary tumors were (18)F-FDG-avid if they displayed focal uptake with an SUVmax 4 or more. Follow-up (18)F-FDG PET/CT was evaluated for recurrent disease. RESULTS: On initial PET/CT, the primary tumor was (18)F-FDG-avid in 236 of 368 (64.1%) and nonavid in 132 patients (35.9%). During follow-up for 18.9 +/- 13.3 mo, 72 patients (19.6%) had recurrence. Of the 63 PET scans with recurrence, 42 (66.7%) and 21 (33.3%) were scans of patients with (18)F-FDG-avid and nonavid primary tumors, respectively. PET sensitivity was higher in scans of patients with (18)F-FDG-avid than nonavid tumors for all recurrences (81.0% vs. 52.4%;P= 0.018) and nonanastomosis site recurrences (82.1% vs. 47.4%; P= 0.006). The sensitivity for detecting peritoneal recurrence was also higher for the avid tumor group. PET specificity was similarly high (97.1% and 97.5%) for both groups. Adding cell type and Lauren classification to tumor(18)F-FDG avidity further enhanced PET sensitivity. CONCLUSION: Surveillance (18)F-FDG PET/CT after resection of gastric cancer has significantly higher sensitivity in patients with (18)F-FDG-avid primary tumors and may have greater value in this group. PMID- 26678616 TI - Gastrointestinal Bleeding Scintigraphy in the Early 21st Century. AB - Gastrointestinal bleeding scintigraphy performed with (99m)Tc-labeled autologous erythrocytes or historically with (99m)Tc-sulfur colloid has been a clinically useful tool since the 1970s. This article reviews the history of the techniques, the different methods of radiolabeling erythrocytes, the procedure, useful indications, diagnostic accuracy, the use of SPECT/CT and CT angiography to evaluate gastrointestinal bleeding, and Meckel diverticulum imaging. The causes of pediatric bleeding are discussed by age. PMID- 26678618 TI - Market watch: Upcoming market catalysts in Q1 2016. PMID- 26678617 TI - Optimized Peptide Amount and Activity for 90Y-Labeled DOTATATE Therapy. AB - In peptide receptor radionuclide therapy with (90)Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely administered in many patients. A higher tumor-to-kidney absorbed dose ratio might be achieved by optimizing the amount of injected peptide and activity, as recent studies have shown different degrees of receptor saturation for normal tissue and tumor. The aim of this work was to develop and implement a modeling method for treatment planning to determine the optimal combination of peptide amount and pertaining therapeutic activity for each patient. METHODS: A whole-body physiologically based pharmacokinetic (PBPK) model was developed. General physiologic parameters were taken from the literature. Individual model parameters were fitted to a series (n= 12) of planar gamma-camera and serum measurements ((111)In-DOTATATE) of patients with meningioma or neuroendocrine tumors (NETs). Using the PBPK model and the individually estimated parameters, we determined the tumor, liver, spleen, and red marrow biologically effective doses (BEDs) for a maximal kidney BED (20 Gy2.5) for different peptide amounts and activities. The optimal combination of peptide amount and activity for maximal tumor BED, considering the additional constraint of a red marrow BED less than 1 Gy15, was individually quantified. RESULTS: The PBPK model describes the biokinetic data well considering the criteria of visual inspection, the coefficients of determination, the relative standard errors (<50%), and the correlation of the parameters (<0.8). All fitted parameters were in a physiologically reasonable range but varied considerably between patients, especially tumor perfusion (meningioma, 0.1-1 mL.g(-1).min(-1), and NETs, 0.02-1 mL.g(-1).min(-1)) and receptor density (meningioma, 5-34 nmol.L(-1), and NETs, 7 35 nmol.L(-1)). Using the proposed method, we identified the optimal amount and pertaining activity to be 76 +/- 46 nmol (118 +/- 71 MUg) and 4.2 +/- 1.8 GBq for meningioma and 87 +/- 50 nmol (135 +/- 78 MUg) and 5.1 +/- 2.8 GBq for NET patients. CONCLUSION: The presented work suggests that to achieve higher efficacy and safety for (90)Y-DOATATE therapy, both the administered amount of peptide and the activity should be optimized in treatment planning using the proposed method. This approach could also be adapted for therapy with other peptides. PMID- 26678619 TI - Monoclonal antibody biosimilars. PMID- 26678621 TI - The drug-target residence time model: a 10-year retrospective. AB - The drug-target residence time model was first introduced in 2006 and has been broadly adopted across the chemical biology, biotechnology and pharmaceutical communities. While traditional in vitro methods view drug-target interactions exclusively in terms of equilibrium affinity, the residence time model takes into account the conformational dynamics of target macromolecules that affect drug binding and dissociation. The key tenet of this model is that the lifetime (or residence time) of the binary drug-target complex, and not the binding affinity per se, dictates much of the in vivo pharmacological activity. Here, this model is revisited and key applications of it over the past 10 years are highlighted. PMID- 26678622 TI - Cyclic vomiting syndrome versus inborn errors of metabolism: A review with clinical recommendations. AB - BACKGROUND: Inborn errors of metabolism are on the differential for patients presenting with a cyclic vomiting syndrome phenotype. Classes of disorders to consider include: mitochondrial disorders, fatty acid oxidation disorders, urea cycle defects, organic acidurias, and acute intermittent porphyria. AIM: This article reviews the metabolic differential diagnosis and approach to screening for inborn errors in children and adults presenting with a cyclic or recurrent vomiting phenotype. CONCLUSION: Cyclic vomiting syndrome is thought to be an episodic syndrome that may be associated with migraine. It is a diagnosis of exclusion. Inborn errors of metabolism should be considered in the patient presenting with a recurrent vomiting phenotype. Mitochondrial dysfunction may play a role in cyclic vomiting syndrome, and true mitochondrial disorders can present with a true cyclic vomiting phenotype. PMID- 26678623 TI - Cardiac muscle mechanics: Sarcomere length matters. PMID- 26678620 TI - Gasotransmitters in cancer: from pathophysiology to experimental therapy. AB - The three endogenous gaseous transmitters - nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) - regulate a number of key biological functions. Emerging data have revealed several new mechanisms for each of these three gasotransmitters in tumour biology. It is now appreciated that they show bimodal pharmacological character in cancer, in that not only the inhibition of their biosynthesis but also elevation of their concentration beyond a certain threshold can exert anticancer effects. This Review discusses the role of each gasotransmitter in cancer and the effects of pharmacological agents - some of which are in early-stage clinical studies - that modulate the levels of each gasotransmitter. A clearer understanding of the pharmacological character of these three gases and the mechanisms underlying their biological effects is expected to guide further clinical translation. PMID- 26678624 TI - Autophagy during cardiac remodeling. AB - Despite progress in cardiovascular research and evidence-based therapies, heart failure is a leading cause of morbidity and mortality in industrialized countries. Cardiac remodeling is a chronic maladaptive process, characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance, and arises from interactions between adaptive modifications of cardiomyocytes and negative aspects of adaptation such as cardiomyocyte death and fibrosis. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components, such as long-lived proteins and organelles. Accumulating evidence demonstrates that autophagy plays an essential role in cardiac remodeling to maintain cardiac function and cellular homeostasis in the heart. This review discusses some recent advances in understanding the role of autophagy during cardiac remodeling. This article is part of a Special Issue entitled: Autophagy in the Heart. PMID- 26678625 TI - [Methodology of the S3 guidelines on alcohol and tobacco-related disorders]. AB - BACKGROUND: From 2010 until 2015 two interdisciplinary evidence-based guidelines were developed to summarize the current knowledge regarding screening, diagnostics and treatment of alcohol and tobacco-related disorders. METHODS: Both guidelines were prepared under the auspices of the German Society for Psychiatry, Psychotherapy and Psychosomatics (Deutsche Gesellschaft fur Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde, DGPPN) and the German Society for Addiction Research and Therapy (Deutsche Gesellschaft fur Suchtforschung und therapie, DG-Sucht). To meet the methodological criteria for the highest quality guidelines (S3 criteria) as defined by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) the following criteria were realized: (1) a systematic search, selection and appraisal of the international literature, (2) a structured process to reach consensus and (3) inclusion of all relevant representatives of future guideline users. RESULTS: More than 60 clinical experts and researchers analyzed the scientific literature. In total 41 international and national guidelines (23 for alcohol and 18 for tobacco) were used. Moreover, 83 systematic Cochrane reviews (alcohol 28, tobacco 55) and 5863 articles (alcohol 2213, tobacco 3650) were analyzed. A total of 7 expert groups formulated 174 recommendations for the screening, diagnosis and treatment of alcohol-related disorders. Six expert groups created 81 recommendations for the screening, diagnosis and treatment of tobacco-related disorders. Approximately 50 scientific associations, professional organizations, patient and family initiatives, as well as representatives of the healthcare system formed a consensus group. In seven 1 and 2-day conferences, all clinical recommendations were discussed and approved by this group. Both guidelines will be revised on a regular basis to guarantee that the clinical recommendations are kept up to date. CONCLUSIONS: Both systematically developed, evidence-based treatment guidelines are comprehensive instruments to provide orientation and assist the decision-making process for physicians, psychologists and other therapists as well as patients and their families in the diagnosis and treatment of alcohol and tobacco use related disorders. PMID- 26678626 TI - Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial. AB - BACKGROUND: Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. STUDY DESIGN: ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. CONCLUSIONS: ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease. PMID- 26678627 TI - Paradigm shift in the intervention for secundum atrial septal defect in an era of transcatheter closure: A national birth cohort study. AB - BACKGROUND: Secundum atrial septal defect (ASDII) is a common congenital heart defect, but the intervention, either transcatheter or surgical, needs are unclear. This study was to examine the paradigm shift in its intervention in an era of transcatheter closure. METHODS AND RESULTS: The study birth cohort 2000 2008 (2,070,145 live births) with complete postnatal medical data was derived from the national database (2000-2014) of Taiwan, a country with national health insurance and easily accessible high-standard medical care. We found 5,515 patients with simple ASDII (median follow-up 12.2 years, one-third diagnosed after age 6 years, incidence 2.66/1,000 live births). Excluding patients with coexisting ventricular septal defect, ASDII intervention was performed in 1,435 of 4,585 patients: transcatheter closure in 1,080 (23.6%) and surgery in 355 (7.8%). The interventional need is 0.69 per 1,000 live births: 0.52 per 1,000 for transcatheter closure and 0.17 per 1,000 for surgery. In the era of transcatheter closure (July 2004-December 2014), ASDII intervention increased to 3.56-fold, but the number of operations decreased to half. The freedom from intervention was lower, and the age at intervention was younger (freedom from intervention at age 6 years, 0.749 vs 0.805, P < .001). In patients born in the era of transcatheter closure, 19.5% (108/555) of the intervention was surgery. Atrioventricular block occurred in 1.12% of those patients after transcatheter closure and none after surgery (P = .149). CONCLUSIONS: In the era of catheter intervention, the interventional criteria for ASDII are less strict and one-third of the patients may receive intervention, mostly transcatheter closure, at the pediatric ages. PMID- 26678628 TI - An international comparison of patients undergoing percutaneous coronary intervention: A collaborative study of the National Cardiovascular Data Registry (NCDR) and Japan Cardiovascular Database-Keio interhospital Cardiovascular Studies (JCD-KiCS). AB - BACKGROUND: Details on Japanese patients undergoing percutaneous coronary intervention (PCI) and how they compare to US patients remain unclear. Furthermore, the application of US risk models has not been evaluated internationally. METHODS: The JCD-KiCS, a multicenter registry of consecutive PCI patients, was launched in 2008, with variables defined in accordance with the US NCDR. Patient and procedural characteristics from patients enrolled from 2008 to 2010 in the JCD-KiCS database (n = 9,941) and those in the NCDR (n = 732,345) were compared. The primary outcomes of this analysis were the hospital-level all cause mortality and bleeding complications. The NCDR risk models for these 2 outcomes were evaluated in the Japanese data set; from the expected mortality and bleeding rates, the observed/expected ratios were calculated. RESULTS: The Japanese patients were older, with a higher proportion of men, diabetes, and smoking than the US patients. The Japanese patients also had a higher rate of complex lesions (26.1 vs 12.7% for bifurcation and 6.2% vs 3.2% for chronic total occlusions, all P < .001), longer procedure time (29.7 +/- 21.5 vs 14.4 +/- 11.5 minutes, P < .001), and higher mortality (1.6% vs 0.9%, P < .001) and bleeding rates (2.9% vs 1.8%, P < .001) compared with US patients. The observed/expected ratios for mortality and bleeding were 0.921 and 0.467, respectively, in Japanese patients, and 1.002 and 0.981, respectively, for US patients. CONCLUSIONS: The characteristics of patients undergoing PCI in clinical practice in Japan and the US differ substantially. The NCDR risk models applied well in Japanese patients for prediction of mortality, but not for bleeding, which tended to underestimate the risk. PMID- 26678629 TI - Clinical characteristics and in hospital outcomes of heart transplant recipients with allograft vasculopathy undergoing percutaneous coronary intervention: Insights from the National Cardiovascular Data Registry. AB - BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted. PMID- 26678630 TI - Perindopril and beta-blocker for the prevention of cardiac events and mortality in stable coronary artery disease patients: A EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) subanalysis. AB - BACKGROUND: beta-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to beta-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including beta-blocker. METHODS: EUROPA was a multicenter, double-blind, placebo controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received beta-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. RESULTS: At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received beta-blocker. Treatment with perindopril/beta-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/beta-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/beta-blocker. CONCLUSIONS: The addition of perindopril to beta-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including beta-blocker. PMID- 26678631 TI - Mortality prediction using a modified Seattle Heart Failure Model may improve patient selection for ventricular tachycardia ablation. AB - BACKGROUND: Catheter ablation is frequently used as a palliative option to reduce shock burden in patients with ventricular tachycardia (VT). A risk prediction tool that accurately predicts short-term survival could improve patient selection for VT ablation. OBJECTIVE: The objective of the study is to assess utility of the Seattle Heart Failure Model (SHFM) to predict 6-month mortality in patients undergoing VT ablation. METHODS: Data on patients who underwent VT ablation at 2 tertiary institutions were retrospectively compiled. The SHFM score at the time of ablation, including 2 added VT variables, was used to predict 6-month mortality. The predicted number of deaths was compared to the observed number to assess model calibration. Model discrimination of those who died within 6 months was assessed by both K- and C-statistics. RESULTS: Mean age of the 243 patients was 63 +/- 12 years; 89% were male. Mean SHFM score for the cohort was 1.3 +/- 1.3. The Kaplan-Meier probability of death within 6 months was 14% (34 patients). The number of deaths estimated by the SHFM at 6 months was 31 (13%) giving a predicted to observed ratio of 0.91 (95% CI 0.64-1.30). The K-statistic for 6 month mortality predictions was 0.77 (95% CI 0.73-0.81), whereas the C-statistic was 0.84 (95% CI 0.78-0.92). Patients with an SHFM score >=4.0 had an estimated positive predictive value of 80% (95% CI 28%-99%) for dying within 6 months of VT ablation. CONCLUSION: The SHFM was well calibrated to a sample of patients who underwent VT ablation and provided good discrimination of short-term deaths. This model could be useful as a prognostic tool to improve patient selection for VT ablation. PMID- 26678632 TI - Association between anxiety and mortality in patients with coronary artery disease: A meta-analysis. AB - BACKGROUND: Depression and anxiety are common in patients with coronary artery disease (CAD). Although depression clearly has been associated with mortality in this population, the relationship between anxiety and mortality is less clear. Accordingly, we performed a series of meta-analyses to (1) examine the relationship between anxiety and mortality in patients with established CAD and (2) determine if this relationship differs in patients with stable CAD compared to those who have just had an acute coronary syndrome (ACS). METHODS AND RESULTS: Systematic literature searches identified 44 articles (total N = 30,527) evaluating the prospective relationship between anxiety and mortality in individuals with established CAD. A series of 8 adjusted and unadjusted meta analyses were performed to examine this relationship across all patients, with sensitivity analyses completed in post-ACS and stable CAD cohorts. In unadjusted analyses, anxiety was associated with a moderate increase in mortality risk (odds ratio 1.21 per SD increase in anxiety). However, when adjusting for covariates, nearly all associations became nonsignificant. In sensitivity analyses, anxiety was associated with an increased risk of poor outcomes in the stable CAD-but not post-ACS-cohort. CONCLUSIONS: These analyses confirm that anxiety is associated with increased risk of mortality in patients with CAD; however, this relationship is not as strong as that of depression and may be explained partly by other clinical factors. If anxiety screening is performed, it should be performed during a period of clinical stability and should target anxiety disorders rather than anxiety symptoms alone. PMID- 26678633 TI - Randomized evaluation of intralesion versus intracoronary abciximab and aspiration thrombectomy in patients with ST-elevation myocardial infarction: The COCTAIL II trial. AB - BACKGROUND: Thrombus burden and distal embolization are predictive of no-reflow during primary percutaneous coronary intervention (PCI) in patients with acute ST elevation myocardial infarction (STEMI). We sought to compare the efficacy of pharmacological and catheter-based strategies for thrombus in patients with STEMI and high atherothrombotic burden. METHODS: Between January 2012 and December 2013, 128 STEMI patients undergoing primary PCI at 5 centers were randomly assigned in a 2 * 2 factorial design to intracoronary (IC) abciximab bolus (via the guide catheter) versus intralesion (IL) abciximab bolus, each with versus without aspiration thrombectomy (AT). Study end points were residual intrastent atherothrombotic burden, defined as the number of cross-sections with residual tissue area >10% as assessed by optical coherence tomography, and indices of angiographic and myocardial reperfusion. RESULTS: Residual intrastent atherothrombotic burden did not significantly differ with IL versus IC abciximab (median [interquartile range] 6.0 [1-15] vs 6.0 [2-11], P = .806) and with AT versus no aspiration (6.0 [1-13] vs 6.0 [2-12], P = .775). Intralesion abciximab administration was associated with improved angiographic myocardial reperfusion in terms of thrombolysis in myocardial infarction (TIMI) flow (3 [3-3] vs 3 [2 3], P = .040), corrected TIMI frame count (12 +/- 5 vs 17 +/- 16, P = .021), and myocardial blush grade (3 [2-3] vs 3 [2-3], P = .035). In particular, IL abciximab was associated with higher occurrence of final TIMI 3 flow (90% vs 73.8%, P = .032) and myocardial blush grade 3 (71.6% vs 52.4%, P = .039). Conversely, AT had no significant effect on indices of angiographic or myocardial reperfusion. CONCLUSIONS: In patients with STEMI and high thrombotic burden, neither IL versus IC abciximab nor AT versus no aspiration reduced postprocedure intrastent atherothrombotic burden in patients with STEMI undergoing primary PCI. However, IL abciximab improved indices of angiographic and myocardial reperfusion compared to IC abciximab, benefits not apparent with AT. PMID- 26678634 TI - Differences in health care use and outcomes by the timing of in-hospital worsening heart failure. AB - BACKGROUND: Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. METHODS: Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). RESULTS: Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. CONCLUSION: Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure. PMID- 26678635 TI - Culprit vessel versus immediate complete revascularization in patients with ST segment myocardial infarction-a systematic review. AB - BACKGROUND: Guidelines suggest percutaneous intervention (PCI) of only the culprit artery in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, recent randomized controlled trials (RCTs) suggest benefit to performing PCI of other stenotic vessels at the same time as culprit vessel PCI. METHODS: We conducted a systematic review with complete case meta-analysis and sensitivity analyses. Data sources included MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and CINAHL from 1946 to March 2014; MEDLINE and EMBASE from March 2014 to March 2015; and scanning of literature for new studies until August 2015. All RCTs comparing multivessel versus culprit-only PCI in patients with STEMI were eligible. The primary outcomes of interest were recurrent myocardial infarction (MI), recurrent revascularization, and mortality. We combined data from trials to estimate the pooled risk ratio (RR) and associated 95% CIs using random-effects models. RESULTS: Five RCTs including 1,606 patients of whom 1,568 had complete data proved eligible. Multivessel revascularization was associated with decreased risk of repeat revascularization (RR 0.36, 95% CI 0.27-0.49, risk difference 9.7% over 2 years) and recurrent nonfatal MI (RR 0.58, 95% CI 0.36-0.93, risk difference 1.8% over 2 years), without increase in mortality (RR 0.82, 95% CI 0.53-1.26) or other adverse events. CONCLUSIONS: Pooled data provide moderate-certainty evidence that performance of multivessel PCI will provide an appreciable reduction in nonfatal MI and high-certainty evidence that it will reduce need for repeat revascularization. Patients are likely to place a high value on these benefits. PMID- 26678636 TI - Cost-effectiveness of edoxaban vs warfarin in patients with atrial fibrillation based on results of the ENGAGE AF-TIMI 48 trial. AB - BACKGROUND: In 21,105 patients with atrial fibrillation (AF), the ENGAGE AF-TIMI 48 trial demonstrated that both higher dose (60mg/30mg dose reduced) and lower dose (30mg/15mg dose reduced) once-daily regimens of edoxaban were non-inferior to warfarin for the prevention of stroke or systemic embolism (SE), with significantly lower rates of bleeding and cardiovascular death. Higher dose edoxaban was associated with a greater reduction in the risk of ischemic stroke than lower dose edoxaban, and the FDA approved higher dose edoxaban in patients with creatinine clearance <=95mL/min. This study evaluated the economic value of higher dose edoxaban vs warfarin based on data from patients in ENGAGE within the FDA-approved population. METHODS: We assessed the cost-effectiveness of edoxaban vs warfarin over a lifetime horizon from the US healthcare system perspective using a Markov model based on a combination of ENGAGE AF-TIMI 48 trial data, US life tables, and published literature on the costs and long-term outcomes of non fatal cardiovascular and bleeding events. Data from the ENGAGE AF-TIMI 48 trial were used to calculate age-adjusted event rates for warfarin and hazard ratios (HRs) for the relative impact of edoxaban on embolic and bleeding complications. Based on the wholesale acquisition price, edoxaban and warfarin were assumed to cost $9.24 and $0.36/day, respectively. RESULTS: For edoxaban vs warfarin, lifetime incremental costs and QALYs were $16,384 and 0.444, respectively, yielding an incremental cost-effectiveness ratio (ICER) of $36,862/QALY gained, using data from patients with creatinine clearance <=95mL/min in ENGAGE AF-TIMI 48. ICERs were more favorable for patients without compared to those with prior warfarin use; ICERs differed minimally by CHADS2 score. CONCLUSIONS: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance <=95mL/min. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of life impact of stroke and bleeding events, and were favorable across both CHADS2 score stroke-risk categories. PMID- 26678637 TI - Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation. AB - BACKGROUND: Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. METHODS: Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. RESULTS: Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P = .0041), major bleedings (P = .0001), vascular death (P < .0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P < .0001). CRP was independently related to myocardial infarction (P = .0047), vascular death (P = .0004), and the composite thromboembolic outcome (P = .0001). When further adjusted for cardiac (troponin and N-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P < .0001), major bleeding (P < .0170) and the composite thromboembolic outcome (P < .0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P = .0017) when adding IL-6 to the clinically used CHA2DS2-VASc risk score with net reclassification improvement of 28%. CONCLUSION: In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction. PMID- 26678638 TI - Hospital variation in admission to intensive care units for patients with acute myocardial infarction. AB - BACKGROUND: The treatment for patients with acute myocardial infarction (AMI) was transformed by the introduction of intensive care units (ICUs), yet we know little about how contemporary hospitals use this resource-intensive setting and whether higher use is associated with better outcomes. METHODS: We identified 114,136 adult hospitalizations for AMI from 307 hospitals in the 2009 to 2010 Premier database using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. Hospitals were stratified into quartiles by rates of ICU admission for AMI patients. Across quartiles, we examined in hospital risk-standardized mortality rates and usage rates of critical care therapies for these patients. RESULTS: Rates of ICU admission for AMI patients varied markedly among hospitals (median 48%, Q1-Q4 20%-71%, range 0%-98%), and there was no association with in-hospital risk-standardized mortality rates (6% all quartiles, P = .7). However, hospitals admitting more AMI patients to the ICU were more likely to use critical care therapies overall (mechanical ventilation [from Q1 with lowest rate of ICU use to Q4 with highest rate 13%-16%], vasopressors/inotropes [17%-21%], intra-aortic balloon pumps [4%-7%], and pulmonary artery catheters [4%-5%]; P for trend < .05 in all comparisons). CONCLUSIONS: Rates of ICU admission for patients with AMI vary substantially across hospitals and were not associated with differences in mortality, but were associated with greater use of critical care therapies. These findings suggest uncertainty about the appropriate use of this resource-intensive setting and a need to optimize ICU triage for patients who will truly benefit. PMID- 26678640 TI - Percutaneous alternative to the Maze procedure for the treatment of persistent or long-standing persistent atrial fibrillation (aMAZE trial): Rationale and design. AB - BACKGROUND: Pulmonary vein antrum isolation (PVI) as a treatment of paroxysmal atrial fibrillation (AF) is associated with a high rate of success; however, outcomes for treating persistent and long-standing persistent AF with PVI alone are substantially lower and often require multiple procedures to maintain long term freedom from atrial arrhythmias. Foci and/or substrate outside the pulmonary veins, particularly in the left atrial appendage (LAA), has been identified as a key mechanism in the maintenance of persistent AF and long-standing persistent AF. OBJECTIVE: The goals of the study are to evaluate the safety and effectiveness of the LARIAT System to percutaneously isolate and ligate the LAA and to determine if LAA ligation as adjunctive therapy to PVI improves maintenance of sinus rhythm in patients with persistent and long-standing persistent AF. STUDY DESIGN: The trial is a prospective, multicenter, randomized controlled study. The trial design incorporates a Bayesian adaptive design that will randomize a maximum of 600 patients with persistent or long-standing persistent AF to LAA ligation and PVI vs PVI alone in a 2:1 randomization. The primary end points include 30-day safety of the LARIAT procedure and freedom from documented AF, atrial flutter, or atrial tachycardia of more than 30 seconds at 12 months after the PVI off antiarrhythmic drugs. Key secondary outcomes include a composite of cardiovascular death and stroke, as well as quality of life. CONCLUSION: The aMAZE trial will determine if LAA ligation as adjunctive therapy to PVI increases the efficacy of maintaining sinus rhythm in patients with persistent and long-standing persistent AF. PMID- 26678639 TI - Serial measurement of N-terminal pro-B-type natriuretic peptide and cardiac troponin T for cardiovascular disease risk assessment in the Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT proBNP further improves prediction. METHODS: Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 +/- 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. RESULTS: Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio [HR] for CHD [95% CI] for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 [1.50-2.76]; HR for CHD for detectable vs undetectable TnT, 3.95 [2.29-6.81]). N-terminal-pro-B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in DeltalogNT-proBNP, 1.95 [1.16-3.26]). None of the observed associations varied by ethnicity. CONCLUSIONS: Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information. PMID- 26678641 TI - Efficacy of colchicine versus placebo for the treatment of pericardial effusion after open-heart surgery: A randomized, placebo-controlled trial. AB - BACKGROUND: Pericardial effusion (PE), a common complication after open-heart surgery, accounts for 50% to 85% of patients. Although reversible in most of the cases, it could be life threatening in the occurrence of tamponade in large effusions. We aimed to determine the therapeutic efficacy of colchicine on PE after open-heart surgery. METHODS: The study is a prospective, randomized, triple blind, placebo-controlled single-center trial at Tehran Heart Center. A total of 149 patients with mild or moderate PE in transthoracic echocardiography were randomly assigned to receive 1 mg/d colchicine (n = 74) or 1 tablet of placebo (n = 75) for 2 weeks and then underwent follow-up echocardiography. RESULTS: Baseline and clinical characteristics were not significantly different between the 2 study groups except for age (P = .02) and graft numbers (P = .005). There was no significant difference in pretreatment and posttreatment PE sizes between the 2 study groups (P = .440 and .844, respectively). Median (25th-75th percentiles) of effusion changes was 5 mm (1-7.6 mm) in the colchicine group and 5 mm (1-6.6 mm) in the placebo group (P = .932). Intervention had no significant impact on pretreatment and posttreatment effusion values and changes in isolated coronary artery bypass graft surgery patients (P = .607, .539, and .628, respectively). After adjustment for possible confounders, there was still no significant difference in postoperative PE between the 2 study groups (t = 0.285, P = .776). CONCLUSION: We concluded that prescription of colchicine does not seem to be effective in treatment of asymptomatic postoperative PE. This could be justified in case that the etiology of most of the PEs might be contribution of noninflammatory factors which are better to be dealt with observational approaches. PMID- 26678642 TI - Blood Pressure Visit Intensification Study in Treatment: Trial design. AB - BACKGROUND: There is a presumption that, for patients with uncontrolled blood pressure (BP), early follow-up, that is, within 4 weeks of an elevated reading, improves BP control. However, data are lacking regarding effective interventions for increasing clinician frequency of follow-up visits and whether such interventions improve BP control. METHODS/DESIGN: Blood Pressure Visit Intensification Study in Treatment involves a multimodal approach to improving intensity of follow-up in 12 community health centers using a stepped wedge study design. DISCUSSION: The study will inform effective interventions for increasing frequency of follow-up visits among patients with uncontrolled BP and determine whether increasing follow-up frequency is associated with better BP control. PMID- 26678643 TI - Trends in acute myocardial infarction hospitalizations: Are we seeing the whole picture? AB - BACKGROUND: Payers and policy makers rely on studies of trends in acute myocardial infarction (AMI) hospitalizations and spending that count only hospitalizations where the AMI is the principal discharge diagnosis. Hospitalizations with AMI coded as a secondary diagnosis are ignored. The effects of excluding these hospitalizations on estimates of trends are unknown. METHODS: Observational study of all AMI hospitalizations in Fee-for-Service Medicare beneficiaries 65 years and older, from 2002 through 2011. RESULTS: We studied 3,663,137 hospitalizations with any AMI discharge diagnosis over 288,873,509 beneficiary-years. Of these, 66% had AMI coded as principal (versus secondary). From 2002 to 2011, AMI hospitalization rates declined 24.5% (from 1,485 per 100,000 beneficiary-years in 2002 to 1,122 in 2011). Meanwhile, the proportion of these hospitalizations with a secondary AMI diagnosis increased from 28% to 40%; by 2011 these secondary AMI hospitalizations accounted for 43% of all expenditures for hospitalizations with AMI, or $2.8 billion. Major changes in comorbidities, principal diagnoses and mean costs for hospitalizations with a non principal AMI diagnosis occurred in the 2006-2008 timeframe. CONCLUSIONS: Current estimates of the burden of AMI ignore an increasingly large proportion of overall AMI hospitalizations and spending. Changes in the characteristics of hospitalizations that coincided with major payment and policy changes suggest that non-clinical factors affect AMI coding. Failing to consider all AMIs could inflate estimates of population health improvements, overestimate the value of AMI prevention and treatment and underestimate current and future AMI burden and expenditures. PMID- 26678644 TI - Individual components of the Romhilt-Estes left ventricular hypertrophy score differ in their prediction of cardiovascular events: The Atherosclerosis Risk in Communities (ARIC) study. AB - BACKGROUND: It has been recently reported that the Romhilt-Estes (R-E) score, originally proposed for detection of left ventricular hypertrophy from the electrocardiogram, is a strong predictor of all-cause mortality. Whether the R-E score is also predictive of cardiovascular disease (CVD) and whether its individual components differ in their ability to predict different CVD outcomes are not well established. METHODS: This analysis includes 13,261 participants from the ARIC study who were free of CVD at baseline (1987-1989). Incident CVD, coronary heart disease (CHD), heart failure (HF), and stroke were ascertained by an adjudication committee through December 2010. The R-E left ventricular hypertrophy score was measured from automatically processed baseline electrocardiogram data. Cox proportional hazard models were used to examine the association between baseline the R-E overall score (overall) and each of its 6 individual components separately, with each of the CVD outcomes. RESULTS: During a median follow-up of 21.8 years, 3,579, 2,205, 1,814, and 731 CVD, CHD, HF, and stroke events, respectively, occurred. In multivariable adjusted models, R-E score >=4 points (compared with 0 points) was associated with increased risk of CVD, CHD, HF, and stroke (hazard ratio [95% CI] 1.66 [1.41-1.96], 1.66 [1.34 2.07], 1.97 [1.60-2.43], and 1.49 [1.07-2.07], respectively). The 6 component of the R-E score varied in their relationship to different CVD outcomes. CONCLUSIONS: The R-E score is predictive of CVD outcomes. The 6 R-E score components differ in their associations with different CVD outcomes, indicating that they may be electrical biomarkers of different physiological events within the myocardium. PMID- 26678645 TI - Collaborative quality improvement vs public reporting for percutaneous coronary intervention: A comparison of percutaneous coronary intervention in New York vs Michigan. AB - INTRODUCTION: Public reporting (PR) is a policy mechanism that may improve clinical outcomes for percutaneous coronary intervention (PCI). However, prior studies have shown that PR may have an adverse impact on patient selection. It is unclear whether alternatives to PR, such as collaborative quality improvement (CQI), may drive improvements in quality of care and outcomes for patients receiving PCI without the unintended consequences seen with PR. METHODS: Using National Cardiovascular Data Registry CathPCI Registry data from January 2011 through September 2012, we evaluated patients who underwent PCI in New York (NY), a state with PR (N = 51,983), to Michigan, a state with CQI (N = 53,528). We compared patient characteristics, the quality of care delivered, and clinical outcomes. RESULTS: Patients undergoing PCI in NY had a lower-risk profile, with a lower proportion of patients with ST-segment elevation myocardial infarction, non ST-segment elevation myocardial infarction, or cardiogenic shock, compared with Michigan. Quality of care was broadly similar in the 2 states; however, outcomes were better in NY. In a propensity-matched analysis, patients in NY were less likely to be referred for emergent, urgent, or salvage coronary artery bypass surgery (odds ratio [OR] 0.67, 95% CI 0.51-0.88, P < .0001) and to receive blood transfusion (OR 0.7, 95% CI 0.61-0.82, P < .0001), and had lower in-hospital mortality (OR 0.72, 95% CI 0.63-0.83, P < .0001). CONCLUSIONS: Public reporting of PCI data is associated with fewer high-risk patients undergoing PCI compared with CQI. However, in comparable samples of patients, PR is also associated with a lower risk of mortality and adverse events. The optimal quality improvement method may involve combining these 2 strategies to protect access to care while still driving improvements in patient outcomes. PMID- 26678646 TI - Antithrombotic strategy variability in ATrial fibrillation and obstructive coronary disease revascularized with PCI-rationale and study design of the prospective observational multicenter AVIATOR 2 registry. AB - BACKGROUND: In the era of novel antithrombotic therapy, the optimal treatment for patients with nonvalvular atrial fibrillation (AF) or flutter undergoing percutaneous coronary intervention (PCI) is undetermined. STUDY DESIGN: The AVIATOR 2 study is a multicenter prospective observational registry that will enroll approximately 2,500 patients with nonvalvular AF or flutter undergoing PCI starting March 2015 over an 18-month enrollment period. Antithrombotic therapy selection will be at the discretion of the treating physician. An integral feature of this study is the use of a smartphone-based survey to capture physician and patient perspectives regarding antithrombotic therapies after PCI. Survey-derived patient treatment concerns, perceived need, and affordability will be used to calculate the risk of non-adherence. Subjective risk for ischemic or bleeding events will be correlated with previously validated risk scores as well as observed event rates at 1, 6, or 12 months post-PCI. ENDPOINTS: The primary efficacy end point will be major adverse cardiac and cerebrovascular events, a composite occurrence of death, nonfatal myocardial infarction, stroke, stent thrombosis, and clinically driven target lesion revascularization at 1 year. The primary safety end point will be major bleeding as per Bleeding Academic Research Consortium criteria types 2, 3, or 5. The secondary end points will include (i) net adverse clinical events, a composite occurrence of all major adverse cardiac and cerebrovascular events, and major bleeding at 1 year; (ii) correlation between estimated subjective and objective (CHADS2, CHA2DS2-VASc, stent thrombosis score, HAS-BLED, and ATRIA scores) ischemic and bleeding risks; (iii) modes of antithrombotic therapy cessation and their impact on outcomes; and (iv) correlation between observed and expected non-adherence to treatment. SUMMARY: AVIATOR 2 is a real-world registry designed to evaluate ischemic and bleeding outcomes according to conventional and novel antithrombotic regimens in patients with nonvalvular AF or flutter undergoing PCI. The study will also provide insights in to physician- and patient-centered factors affecting treatment selection and adherence and their overall impact on clinical outcomes. The study is registered on clinicaltrials.gov NCT02362659. PMID- 26678648 TI - Validation of the modified Sgarbossa criteria for acute coronary occlusion in the setting of left bundle branch block: A retrospective case-control study. AB - BACKGROUND: The modified Sgarbossa criteria were proposed in a derivation study to be superior to the original criteria for diagnosing acute coronary occlusion (ACO) in left bundle branch block (LBBB). The new rule replaces the third criterion (5 mm of excessively discordant ST elevation [STE]) with a proportion (at least 1 mm STE and STE/S wave <=-0.25). We sought to validate the modified criteria. METHODS: This retrospective case-control study was performed by chart review in 2 tertiary care center emergency departments (EDs) and 1 regional referral center. A billing database was used at 1 site to identify all ED patients with LBBB and ischemic symptoms between May 2009 and June 2012. In addition, all 3 sites identified LBBB ACO patients who underwent emergent catheterization. We measured QRS amplitude and J-point deviation in all leads, blinded to outcomes. Acute coronary occlusion was determined by angiographic findings and cardiac biomarker levels, which were collected blinded to electrocardiograms. Diagnostic statistics of each rule were calculated and compared using McNemar's test. RESULTS: Our consecutive cohort search identified 258 patients: 9 had ACO, and 249 were controls. Among the 3 sites, an additional 36 cases of ACO were identified, for a total of 45 ACO cases and 249 controls. The modified criteria were significantly more sensitive than the original weighted criteria (80% vs 49%, P < .001) and unweighted criteria (80% vs 56%, P < .001). Specificity of the modified criteria was not statistically different from the original weighted criteria (99% vs 100%, P = .5) but was significantly greater than the original unweighted criteria (99% vs 94%, P = .004). CONCLUSIONS: The modified Sgarbossa criteria were superior to the original criteria for identifying ACO in LBBB. PMID- 26678649 TI - Primary cutaneous and subcutaneous leiomyosarcomas: evolution and prognostic factors. AB - Cutaneous and subcutaneous leiomyosarcomas (LMS) are uncommon neoplasms. We reviewed the MEDLINE database to assess their rates of recurrence and metastasis, mortality and recommended follow-up period. Other prognostic factors were also studied. This review included 112 subcutaneous LMS and 313 cutaneous LMS. In subcutaneous LMS, we observed that rates of recurrence, metastasis and mortality were 36.63%, 43.23% and 37.82%, respectively, after a median follow-up period of 4.40 years, while in cutaneous LMS those figures were 24.40%, 4.22% and 3.33%, respectively, after a median follow-up period of 3.45 years. Although subcutaneous and cutaneous LMS show similar morphologic features, the latter show less tendency to recur and metastasize; in certain cases they both may be the cause of death. For these reasons we suggest avoiding the term "atypical intradermal smooth muscle neoplasm". Location, size and histologic grade are essential prognostic factors for superficial LMS. Recurrence after incomplete excision can be avoided when performed with a surgical margin of at least 1 cm. Follow-up should be at least five years. PMID- 26678647 TI - Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE). AB - BACKGROUND: Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. METHODS: CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 +/- 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. RESULTS: Overall, CFR (mean 2.61 +/- 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = 0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR <=2.5 versus those with CFR >2.5 had greater aPWV (894 +/- 117 vs 747 +/- 93 cm/s, P < .001), augmented pressure (14 +/- 4.9 vs 11 +/- 4.1 mmHg, P < .008), AIx (32 +/- 6.6 vs 27 +/- 6.6%, P < .003), LVEw (30 +/- 12 vs 21 +/- 10 dyne-s/cm(2) * 10(2), P < .02) and reduced pulse pressure amplification (1.20 +/- .07 vs 1.26 +/- .10, P < .008) and pressure wave travel time (133 +/- 7.3 vs 138 +/- 6.9 milliseconds, P < .04). CONCLUSIONS: Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia. PMID- 26678650 TI - Privacy-preserving search for chemical compound databases. AB - BACKGROUND: Searching for similar compounds in a database is the most important process for in-silico drug screening. Since a query compound is an important starting point for the new drug, a query holder, who is afraid of the query being monitored by the database server, usually downloads all the records in the database and uses them in a closed network. However, a serious dilemma arises when the database holder also wants to output no information except for the search results, and such a dilemma prevents the use of many important data resources. RESULTS: In order to overcome this dilemma, we developed a novel cryptographic protocol that enables database searching while keeping both the query holder's privacy and database holder's privacy. Generally, the application of cryptographic techniques to practical problems is difficult because versatile techniques are computationally expensive while computationally inexpensive techniques can perform only trivial computation tasks. In this study, our protocol is successfully built only from an additive-homomorphic cryptosystem, which allows only addition performed on encrypted values but is computationally efficient compared with versatile techniques such as general purpose multi-party computation. In an experiment searching ChEMBL, which consists of more than 1,200,000 compounds, the proposed method was 36,900 times faster in CPU time and 12,000 times as efficient in communication size compared with general purpose multi-party computation. CONCLUSION: We proposed a novel privacy-preserving protocol for searching chemical compound databases. The proposed method, easily scaling for large-scale databases, may help to accelerate drug discovery research by making full use of unused but valuable data that includes sensitive information. PMID- 26678651 TI - Demographic factors associated with loss to follow up in the management of chronic otitis media: case-control study. AB - OBJECTIVE: The likelihood of a patient attending regular follow up can affect decision making when planning and performing tympanomastoid surgery. This study investigated whether demographic factors were associated with loss to follow up. METHODS: A database of patients who had been investigated and treated for chronic otitis media was searched. Patients lost to follow up and a matching sample of patients who were formally discharged were identified. The demographic factors of age, sex and postcode were compared between the two groups. The information collected was also used to provide measures of deprivation. RESULTS: Fifty patients in each group were identified. Patients lost to follow up were significantly younger than patients formally discharged (p < 0.02), and were more likely to live in an area of education and training deprivation (p < 0.05). CONCLUSION: Younger patient age, and living in an area of education and training deprivation, are associated with a higher incidence of loss to follow up. PMID- 26678652 TI - Balance, dizziness and proprioception in patients with chronic whiplash associated disorders complaining of dizziness: A prospective randomized study comparing three exercise programs. AB - BACKGROUND: Dizziness and unsteadiness are common symptoms following a whiplash injury. OBJECTIVE: To compare the effect of 3 exercise programs on balance, dizziness, proprioception and pain in patients with chronic whiplash complaining of dizziness. DESIGN: A sub-analysis of a randomized study. METHODS: One hundred and forty subjects were randomized to either a physiotherapist-guided neck specific exercise (NSE), physiotherapist-guided neck-specific exercise, with a behavioural approach (NSEB) or prescription of general physical activity (PPA) group. Pre intervention, 3, 6 and 12 months post baseline they completed the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ), Visual Analogue Scales (VAS) for, dizziness at rest and during activity and physical measures (static and dynamic clinical balance tests and head repositioning accuracy (HRA)). RESULTS: There were significant time by group differences with respect to dizziness during activity and UCLA-Q favouring the physiotherapy led neck specific exercise group with a behavioural approach. Within group analysis of changes over time also revealed significant changes in most variables apart from static balance. CONCLUSION: Between and within group comparisons suggest that physiotherapist led neck exercise groups including a behavioural approach had advantages in improving measures of dizziness compared with the general physical activity group, although many still complained of dizziness and balance impairment. Future studies should consider exercises specifically designed to address balance, dizziness and cervical proprioception in those with persistent whiplash. PMID- 26678653 TI - Acanthamoeba and other free-living amoebae in bat guano, an extreme habitat. AB - Several representatives of the so-called free-living amoebae (FLA) are of medical relevance, not only as facultative pathogens but also as vehicles for pathogenic bacteria. Some FLA can survive and even grow under extreme environmental conditions. Bat guano is an exceptional habitat, the conditions becoming gradually more extreme with aging. In the current study, samples of bat guano of different ages from five caves in Slovenia were screened for the presence of FLA. FLA were isolated from almost all guano samples, including guano with a pH of 3.5. Only the two samples that had been drawn from >20-year-old guano were negative for FLA. Generally, FLA diversity correlated to high concentrations of cultivable bacteria (~10(8) CFU/g) and fungi (~10(5) CFU/g). Interestingly, the absence of FLA in seasoned guanos was mirrored by the presence of dictyostelid slime moulds. The isolated amoebae were identified as belonging to the genera Acanthamoeba, Copromyxa, Naegleria, Sappinia, Tetramitus, Thecamoeba, Vahlkampfia, Vannella and Vermamoeba. To the best of our knowledge, this is the first study on the diversity of FLA in guano. PMID- 26678654 TI - In vitro excystation of Cryptosporidium muris oocysts and viability of released sporozoites in different incubation media. AB - This study aimed to evaluate and document the excystation process of Cryptosporidium muris oocysts in various incubation media, and to monitor the behaviour of excysting and freshly excysted sporozoites. A test of oocyst viability, using fluorescent double staining with fluorescein diacetate and propidium iodide, was performed prior to each experimental assay. Light microscope observations confirmed that relatively often only three sporozoites were released; the fourth one either left the oocyst later together with a residual body or remained trapped within the oocyst wall. These results suggest that successful oocyst excystation is not limited by the viability of all four sporozoites. Darkening of oocysts to opaque and their specific movement (the so called "oocyst dancing") preceded the final excystation and liberation of sporozoites, while the dormant oocysts appeared refractive. The process of excystation in C. muris is not gradual as generally described in cryptosporidia but very rapid in an eruptive manner. Experiments were performed using oocysts stored at 4 degrees C for various time periods, as well as oocysts freshly shed from host rodents (Mastomys coucha) of different ages. The most suitable medium supporting high excystation rate (76 %) and prolonged motility of sporozoites was RPMI 1640, enriched with 5 % bovine serum albumin (BSA). Our results emphasize that to reliably evaluate the success of in vitro excystation of cryptosporidia, not only the number of released sporozoites in a set time period should be taken into consideration but also their subsequent activity (motility), as it is expected to be essential for the invasion of host cells. PMID- 26678655 TI - C-Reactive Protein as a New Prognostic Factor for Survival in Patients With Pancreatic Neuroendocrine Neoplasia. AB - CONTEXT: Patients with pancreatic neuroendocrine neoplasia (pNEN) show great variability in prognosis and treatment response. Additional prognostic markers might help in individual therapeutic decision making. OBJECTIVE: The objective of the study was to investigate the association between preoperative plasma levels of C-reactive protein (CRP) and overall survival (OS) in pNEN. DESIGN: This was a single-center, retrospective analysis of long-term prospective patient-database. SETTING: The study was conducted at a tertiary referral center. PATIENTS: All 149 patients with sporadic pNENs were eligible for retrospective analysis. MAIN OUTCOME MEASURE: Cumulative overall survival, compared between patients with elevated and normal CRP levels, was measured. RESULTS: Median OS for patients with elevated CRP levels was 1093 days (SE 1261, 95% confidence interval [CI] 0 3565), compared with 6859 days (SE 1252, 95% CI 4405-9313) for patients with normal CRP levels. Log rank test showed a significant correlation between CRP and OS (P < .001). In univariate Cox regression, patients with elevated CRP levels had a significantly higher hazard ratio for death (3.27; 95%-CI 1.74-6.16; P < .001). This finding persisted after multivariable adjustment. Furthermore, OS was associated with the presence of liver metastases (hazard ratio 3.17; 95% CI 1.88 5.35; P < .001), incomplete resection (R1/R2 status; hazard ratio 3.99; 95% CI 2.16-7.35; P < .001) and Ki-67 percentage (hazard ratio 5.05; 95% CI 2.17-11.76; P < .001). CONCLUSION: CRP is an independent prognostic marker in patients with pNEN. Pretreatment CRP measurements should be considered for incorporation into prospective studies of outcome in patients with pNENs and clinical trials of systemic therapies for these tumors. PMID- 26678656 TI - Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study. AB - CONTEXT: Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear. OBJECTIVE: The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies. DESIGN: This was a retrospective, controlled, cohort study. SETTING: The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people. PATIENTS: A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE: Five-year survival after the start of GLA was measured. RESULTS: Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival. CONCLUSIONS: Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts. PMID- 26678657 TI - Neuroendocrine Tumor of the Pancreas as a Manifestation of Cowden Syndrome: A Case Report. AB - CONTEXT: Germline mutations in the phosphatase and tensin homolog (PTEN) tumor suppressor gene are found in the majority of patients with Cowden syndrome (CS), who have an increased risk of breast, thyroid, and endometrial cancer. According to our current understanding of genetic changes in the PTEN gene and the resultant phenotypic features of CS, pancreatic neuroendocrine tumors (NETs) are not considered part of the clinical spectrum of CS. CASE DESCRIPTION: We report a unique case of an advanced NET of the pancreas in a patient with CS. The germline DNA sequencing confirmed the clinical diagnosis of CS and revealed a PTEN mutation c.697C->T (p.R233*) causing a premature stop codon in exon 7. The tumor DNA sequencing showed no loss of heterozygosity or any copy number changes and no other deleterious genetic alterations, including those commonly mutated in sporadic pancreatic NETs: MEN1, ATRX, DAXX, TP53, and genes involved in the mammalian target of rapamycin pathway. In addition, the high-throughput transcriptome analyzed by RNA-seq did not reveal any missed genetic alterations, aberrant splicing variants, gene fusions, or gene expression alterations. The immunohistochemical staining of the tumor for PTEN revealed an abnormal, uniformly strong cytoplasmic staining of tumor cells with virtually absent nuclear staining. CONCLUSION: The results from genetic testing and histopathological techniques used to confirm CS diagnosis and characterize this unusual tumor tempted us to believe that in this case, the pancreatic NET was not a sporadic malignancy that occurred by coincidence, but rather represented a new entity in the spectrum of malignancies associated with CS. PMID- 26678658 TI - Intimate partner violence: Are the risk factors similar for men and women, and similar to other types of offending? AB - We studied intimate partner violence (IPV) within a framework of other violent and nonviolent offending, to explore whether the risk factors for offending were similar across the different offense categories, and also for men and women. A comprehensive measure of offending behavior was administered to 184 men and 171 women, together with measures of anger, self-control, and psychopathic traits. The measure, the nonviolent and violent offending behavior scale (NVOBS), assesses IPV, general violence, and nonviolent offending behavior. Men perpetrated higher levels of general violence and nonviolent offenses than women, whereas women perpetrated significantly more IPV than men. Regression analyses showed that the predictors of offending behavior are generally similar for men and women, with the exception of IPV, where self-control was a better predictor of IPV for men and anger was a better predictor of IPV for women. Limitations of the present sample and suggestions for future work are discussed. Aggr. Behav. 42:404-412, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26678659 TI - Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications. AB - PURPOSE: To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. METHODS AND MATERIALS: The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped (60)Co heads. The unit is supported by a Monte Carlo-based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient at the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. RESULTS: The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. CONCLUSION: Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites. PMID- 26678660 TI - Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study. AB - PURPOSE: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). METHODS AND MATERIALS: We enrolled patients with a >=6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of <=3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with ClinicalTrials.gov (clinicaltrials.gov identifier NCT01046123). RESULTS: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. CONCLUSIONS: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases. PMID- 26678661 TI - MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells. AB - PURPOSE: We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved. METHODS AND MATERIALS: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR 203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed. RESULTS: Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced gamma-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1alpha, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1. CONCLUSIONS: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM. PMID- 26678662 TI - Pathophysiological effects of Cerastes cerastes and Vipera lebetina venoms: Immunoneutralization using anti-native and anti-(60)Co irradiated venoms. AB - Cerastes cerastes and Vipera lebetina are the most medically important vipers in Algeria. Their bite induces several pathological effects on victims of accidental envenomation. In this study we analyzed the pathogenesis induced after an experimental envenomation. Indeed, we determined, in vitro, venom enzymatic activities and we analyzed, in vivo, pathological effects induced on liver, heart, lung and skin. In addition we investigated the neutralizing potency of four experimental antivenoms elicited against native and irradiated venoms. Results revealed that V. lebetina and Cerastes cerastes venoms presented strong hemorrhagic, oedematic and necrotic activities. Histopathological study showed that both venoms induced deep damage in tissue structures leading to organ dysfunction. They also increased cellular peroxidases activities, indicating an inflammatory process that is known to amplify tissue damage. Western-blot analysis evidenced that anti-irradiated venoms recognized most components of native venoms. Antivenoms were effective in neutralizing all tested activities, with an increased protective effect obtained with anti-irradiated venoms. Anti irradiated venoms reduced cellular peroxidases activities indicating a reduction of the inflammatory response. These results may improve our understanding of Algerian Viperidae bite pathogenesis and would encourage further studies planning to provide more proofs on the effectiveness of anti-irradiated venoms administration in the treatment of envenomation. PMID- 26678664 TI - Hydrogen Sulfide Activates S-Type Anion Channel via OST1 and Ca(2+) Modules. PMID- 26678663 TI - EC: an efficient error correction algorithm for short reads. AB - BACKGROUND: In highly parallel next-generation sequencing (NGS) techniques millions to billions of short reads are produced from a genomic sequence in a single run. Due to the limitation of the NGS technologies, there could be errors in the reads. The error rate of the reads can be reduced with trimming and by correcting the erroneous bases of the reads. It helps to achieve high quality data and the computational complexity of many biological applications will be greatly reduced if the reads are first corrected. We have developed a novel error correction algorithm called EC and compared it with four other state-of-the-art algorithms using both real and simulated sequencing reads. RESULTS: We have done extensive and rigorous experiments that reveal that EC is indeed an effective, scalable, and efficient error correction tool. Real reads that we have employed in our performance evaluation are Illumina-generated short reads of various lengths. Six experimental datasets we have utilized are taken from sequence and read archive (SRA) at NCBI. The simulated reads are obtained by picking substrings from random positions of reference genomes. To introduce errors, some of the bases of the simulated reads are changed to other bases with some probabilities. CONCLUSIONS: Error correction is a vital problem in biology especially for NGS data. In this paper we present a novel algorithm, called Error Corrector (EC), for correcting substitution errors in biological sequencing reads. We plan to investigate the possibility of employing the techniques introduced in this research paper to handle insertion and deletion errors also. SOFTWARE AVAILABILITY: The implementation is freely available for non-commercial purposes. It can be downloaded from: http://engr.uconn.edu/~rajasek/EC.zip. PMID- 26678665 TI - Attentional enhancement for positive and negative tones at an early stage of auditory processing. AB - We report an event-related potential (ERP) study based on the hypothesis that valenced (i.e., positive and/or negative) tones are prioritized over neutral ones at an early, perceptual stage of auditory processing. In order to avoid perceptual confounds, we induced valence experimentally during a learning phase by assigning positive, negative, and neutral valences to tone-frequencies in a balanced design. In a subsequent test phase, EEG was recorded while these tones were entirely task-irrelevant. The amplitude of the auditory N1 was increased for valenced compared with neutral tones, indicating enhanced attention. While behavioral results of the learning phase, and both implicit and explicit measures of tone evaluation indicated differentiation between positive and negative valence, there was no such differentiation on the N1 amplitude. Our results suggest that it is the general relevance of the valenced tones that governs early attentional processes. PMID- 26678667 TI - Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer. AB - Thyroid cancer is the most common endocrine malignancy and accounts for nearly 1% of all of human cancer. Thyroid cancer has four main histological types: papillary, follicular, medullary, and anaplastic. Papillary, follicular, and anaplastic thyroid carcinomas are derived from follicular thyroid cells, whereas medullary thyroid carcinoma (MTC) originates from the neural crest parafollicular cells or C-cells of the thyroid gland. MTC represents a neuroendocrine tumor and differs considerably from differentiated thyroid carcinoma. MTC is one of the aggressive types of thyroid cancer, which represents 3-10% of all thyroid cancers. It occurs in hereditary (25%) and sporadic (75%) forms. The hereditary form of MTC has an autosomal dominant mode of inheritance. According to the present classification, hereditary MTC is classified as a multiple endocrine neoplasi type 2 A & B (MEN2A & MEN2B) and familial MTC (FMTC). The RET proto oncogene is located on chromosome 10q11.21. It is composed of 21 exons and encodes a transmembrane receptor tyrosine kinase. RET regulates a complex network of signal transduction pathways during development, survival, proliferation, differentiation, and migration of the enteric nervous system progenitor cells. Gain of function mutations in RET have been well demonstrated in MTC development. Variants of MTC result from different RET mutations, and they have a good genotype-phenotype correlation. Various MTC related mutations have been reported in different exons of the RET gene. We proposed that RET genetic mutations may be different in distinct populations. Therefore, the aim of this study was to find a geographical pattern of RET mutations in different populations. PMID- 26678666 TI - Heart rate variability and plasma biomarkers in patients with type 1 diabetes mellitus: Effect of a bout of aerobic exercise. AB - OBJECTIVE: The aim of this study was to evaluate: (1) the cardiovascular parameters and plasma biomarkers in people with type 1 diabetes mellitus (T1DM) at baseline; and (2) the heart rate variability (HRV) and blood glucose in response to a session of aerobic exercise (AE) and during recovery period. RESEARCH DESIGN AND METHODS: Adults (18-35 years) were divided into two groups: control (CT, n=10) and T1DM (n=9). Anthropometric, cardiovascular, and biochemical parameters, and aerobic capacity (indirect peak oxygen uptake, VO2peak) were evaluated at baseline. Thirty minutes of AE (40-60% intensity) was performed on a treadmill. Blood glucose and HRV were determined at rest, during AE, and during the recovery period. RESULTS: Anthropometric measurements, cardiovascular parameters, aerobic capacity, and biochemical parameters were similar between the groups at baseline. In the T1DM group, blood glucose, glycated hemoglobin, and thiobarbituric acid reactive substances concentrations were increased while nitrite/nitrate (NOx(-)) levels were reduced. During AE, the magnitude of the reduction of blood glucose was greater than that during the recovery period in the T1DM group. The RR intervals and SDNN were reduced at rest as well as in the recovery period in T1DM subjects, whereas the RMSSD and pNN50 were only reduced during the recovery period. No changes were observed in low frequency (LF), high frequency (HF), and LF/HF ratio. CONCLUSION: Our study shows that T1DM patients on insulin therapy have poor blood glucose control with greater lipid peroxidation and lower NOx(-) levels, accompanied by an imbalance in autonomic function detected by the challenge of AE. PMID- 26678668 TI - Epidemiology of invasive respiratory disease caused by emerging non-Aspergillus molds in lung transplant recipients. AB - OBJECTIVES: Our aim was to assess the impact of positive cultures for non Aspergillus molds on the risk of progression to invasive fungal infection (IFI), and the effect of prophylactic nebulized liposomal amphotericin B (n-LAB) on these pathogens. METHODS: This was an observational study (2003-2013) including lung transplant recipients (LTR) receiving lifetime n-LAB prophylaxis, in whom non-Aspergillus molds were isolated on respiratory culture before and after transplantation (minimum 1-year follow-up). RESULTS: We studied 412 patients, with a mean postoperative follow-up of 2.56 years (interquartile range 1.01 4.65). Pre- and post-transplantation respiratory samples were frequently positive for non-Aspergillus molds (11.9% and 16.9% of LTR respectively). Post transplantation, 10 (2.42%) patients developed non-Aspergillus mold infection (4 Scedosporium species, 4 Purpureocillium species, 1 Penicillium species, and 1 Scopulariopsis species); 5 (1.21%) had IFI, with 60% IFI-related mortality. Non Aspergillus molds with intrinsic amphotericin B (AB) resistance were more commonly isolated in bronchoscopy samples than AB-variably sensitive or AB sensitive molds (54.5% vs. 25%, P = 0.04) and were associated with a higher risk of infection (56.3% vs. 1.3%%, P < 0.01). CONCLUSIONS: In LTR undergoing n-LAB prophylaxis, pre- and post-transplantation isolation of non-Aspergillus molds is frequent, but IFI incidence (1.21%) is low. Purpureocillium is an emerging mold. AB-resistant non-Aspergillus species were found more often in bronchoscopy samples and were associated with a higher risk of infection. PMID- 26678669 TI - Complete mitochondrial genomes of two subspecies (Rhinolophus ferrumequinum nippon and Rhinolophus ferrumequinum tragatus) of the greater horseshoe bat (Chiroptera: Rhinolophidae). AB - Rhinolophus ferrumequinum nippon and Rhinolophus ferrumequinum tragatus are two subspecies of Rhinolophus ferrumequinum currently recognized in China. In this study, their mitochondrial genomes were completely sequenced and annotated. Phylogenetic analyses indicated that R. f. nippon has a close relationship with two subspecies of R. ferrumequinum from Korea with 0.1% divergence, which indicated they are synonyms. PMID- 26678670 TI - Simultaneous determination of neonicotinoid insecticides in sunflower-treated seeds (hull and kernel) by LC-MS/MS. AB - A validated analytical method to determine seven neonicotinoids (dinotefuran, nitenpyram, thiamethoxam, clothianidin, imidacloprid, acetamiprid and thiacloprid) in sunflower seeds (hull and kernel) using HPLC coupled to electrospray ionisation mass spectrometry (ESI-MS) is presented. Sample clean-up based on a solid-liquid extraction, and the removal of lipid fraction, in the case of kernels, is proposed and optimised. Low limits of detection and quantification were obtained, ranging from 0.3 * 10(-3) to 1.2 * 10(-3) ug g(-1) and from 1.0 * 10(-3) to 4.0 * 10(-3) ug g(-1), with good precision, and recovery values ranged from 90% to 104% for hulls and kernels. The method was applied for the analysis of five thiamethoxam-dressed sunflower seeds and four non-treated seeds, where, besides thiamethoxam, residues of the other neonicotinoid, clothianidin, were also detected and confirmed via tandem mass spectrometry (LC ESI-MS/MS). Finally, the presence of residues of thiamethoxam and clothianidin in collected sunflower seeds (hulls) coming from coated seeds confirmed the translocation of these neonicotinoids through the plant up to these seeds. PMID- 26678671 TI - Transcriptomic analysis reveals specific osmoregulatory adaptive responses in gill mitochondria-rich cells and pavement cells of the Japanese eel. AB - BACKGROUND: Homeostasis of ions and water is important for the maintenance of cellular functions. The regulation of the homeostasis is particularly important in euryhaline fish that migrate between freshwater (FW) and seawater (SW) environments. The fish gill, the major tissue that forms an interface separating the extracellular fluids and external water environment, has an effective transport system to maintain and regulate a constant body osmolality. In fish gills, the two major epithelial cells, pavement cells (PVCs) and mitochondria rich cells (MRCs), are known to play key and complementary roles in ion transport at the interface. Discovering the robust mechanisms underlying the two cell types' response to osmotic stress would benefit our understanding of the fundamental mechanism allowing PVCs and MRCs to handle osmotic stress. Owing to the limited genomic data available on estuarine species, existing knowledge in this area is slim. In this study, transcriptome analyses were conducted using PVCs and MRCs isolated from Japanese eels adapted to FW or SW environments to provide a genome-wide molecular study to unravel the fundamental processes at work. RESULTS: The study identified more than 12,000 transcripts in the gill cells. Interestingly, remarkable differential expressed genes (DEGs) were identified in PVCs (970 transcripts) instead of MRCs (400 transcripts) in gills of fish adapted to FW or SW. Since PVCs cover more than 90 % of the gill epithelial surface, the greater change in gene expression patterns in PVCs in response to external osmolality is anticipated. In the integrity pathway analysis, 19 common biological functions were identified in PVCs and MRCs. In the enriched signaling pathways analysis, most pathways differed between PVCs and MRCs; 14 enriched pathways were identified in PVCs and 12 in MRCs. The results suggest that the osmoregulatory responses in PVCs and MRCs are cell-type specific, which supports the complementary functions of the cells in osmoregulation. CONCLUSIONS: This is the first study to provide transcriptomic analysis of PVCs and MRCs in gills of eels adapted to FW or SW environments. It describes the cell-type specific transcriptomic network in different tonicity. The findings consolidate the known osmoregulatory pathways and provide molecular insight in osmoregulation. The presented data will be useful for researchers to select their targets for further studies. PMID- 26678672 TI - Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS). AB - BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women. PMID- 26678673 TI - Skin tumor development after UV irradiation and photodynamic therapy is unaffected by short-term pretreatment with 5-fluorouracil, imiquimod and calcipotriol. An experimental hairless mouse study. AB - BACKGROUND: Photodynamic therapy (PDT) delays ultraviolet (UV) radiation-induced squamous cell carcinomas (SCCs) in hairless mice. Efficacy may be enhanced by combining PDT with antineoplastic or pro-differentiating agents. We investigated if pretreatment with 5-fluorouracil (5FU), imiquimod (IMIQ) or calcipotriol (CAL) before PDT further delays tumor onset. METHODS: Hairless mice (n=224) were exposed 3 times weekly to 3 standard erythema doses (SED) of UV radiation. Methyl aminolevulinate (MAL)-PDT sessions were given on days 45 and 90 before SCC development. Three applications of topical 5FU, IMIQ or CAL were given before each PDT session. Fluorescence photography quantified protoporphyrin IX (PpIX) formation. RESULTS: PDT delayed UV-induced SCC development by 59 days (212 days UV-MAL-PDT vs. 153 days UV-control, P<0.001). Pretreatment with 5FU, IMIQ or CAL before PDT did not further delay SCC onset compared to PDT alone (207 days UV-5FU MAL-PDT, 215 days UV-IMIQ-MAL-PDT, 206 days UV-CAL-MAL-PDT vs. 212 days UV-MAL PDT, P=ns). PpIX fluorescence intensified by 5FU-pretreatment (median 21,392 au UV-5FU-MAL-PDT, P=0.011), decreased after IMIQ-pretreatment (12,452 au UV-IMIQ MAL-PDT, P<0.001), and was unaffected by CAL-pretreatment (19,567 au UV-CAL-MAL PDT, P=ns) compared to MAL alone (18,083 au UV-MAL-PDT). CONCLUSIONS: Short-term three-day pretreatment with 5FU, IMIQ and CAL before PDT does not further delay tumor onset in UV-exposed hairless mice. PMID- 26678674 TI - Evidence of Common Genetic Overlap Between Schizophrenia and Cognition. AB - Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E 04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E 03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. PMID- 26678676 TI - Managing the trauma patient presenting with the lethal triad. PMID- 26678675 TI - Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. AB - Glioblastoma is the most common and aggressive primary brain malignancy. Phenethyl isothiocyanate (PEITC), a member of the isothiocyanate family, can induce apoptosis in many human cancer cells. Our previous study disclosed that PEITC induces apoptosis through the extrinsic pathway, dysfunction of mitochondria, reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress, and intrinsic (mitochondrial) pathway in human brain glioblastoma multiforme (GBM) 8401 cells. To the best of our knowledge, we first investigated the effects of PEITC on the genetic levels of GBM 8401 cells in vitro. PEITC may induce G0/G1 cell-cycle arrest through affecting the proteins such as cdk2, cyclin E, and p21 in GBM 8401 cells. Many genes associated with cell-cycle regulation of GBM 8401 cells were changed after PEITC treatment: 48 genes were upregulated and 118 were downregulated. The cell-division cycle protein 20 (CDC20), Budding uninhibited by benzimidazole 1 homolog beta (BUB1B), and cyclin B1 were downregulated, and clusterin was upregulated in GBM 8401 cells treated with PEITC. These changes of gene expression can provide the effects of PEITC on the genetic levels and potential biomarkers for glioblastoma. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 176-187, 2017. PMID- 26678677 TI - Plasma-Wave Terahertz Detection Mediated by Topological Insulators Surface States. AB - Topological insulators (TIs) represent a novel quantum state of matter, characterized by edge or surface-states, showing up on the topological character of the bulk wave functions. Allowing electrons to move along their surface, but not through their inside, they emerged as an intriguing material platform for the exploration of exotic physical phenomena, somehow resembling the graphene Dirac cone physics, as well as for exciting applications in optoelectronics, spintronics, nanoscience, low-power electronics, and quantum computing. Investigation of topological surface states (TSS) is conventionally hindered by the fact that in most of experimental conditions the TSS properties are mixed up with those of bulk-states. Here, we activate, probe, and exploit the collective electronic excitation of TSS in the Dirac cone. By engineering Bi2Te(3-x)Sex stoichiometry, and by gating the surface of nanoscale field-effect-transistors, exploiting thin flakes of Bi2Te2.2Se0.8 or Bi2Se3, we provide the first demonstration of room-temperature terahertz (THz) detection mediated by overdamped plasma-wave oscillations on the "activated" TSS of a Bi2Te2.2Se0.8 flake. The reported detection performances allow a realistic exploitation of TSS for large-area, fast imaging, promising superb impacts on THz photonics. PMID- 26678678 TI - High-glucose environment increased thrombospondin-1 expression in keratinocytes via DNA hypomethylation. AB - Diabetes is an important health issue because of its increasing prevalence and association with impaired wound healing. Epidermal keratinocytes with overexpressed antiangiogenic molecule thrombospondin-1 (TSP1) have been shown to impair proper wound healing. This study examined the potential involvement of keratinocyte-derived TSP1 on diabetic wound healing. Cultured human keratinocytes and diabetic rat model were used to evaluate the effect of high-glucose environment on TSP1 expression in epidermal keratinocytes, and the molecular mechanisms involved in the process were also studied. We demonstrated that high glucose environment increased TSP1 expression in keratinocytes. In addition, increased oxidative stress induced DNA hypomethylation at the TSP1 promoter region in keratinocytes exposed to high-glucose environment. Similar findings were found in our diabetic rat model. Early antioxidant administration normalized TSP1 expression and global DNA methylation status in diabetic rat skin and improved wound healing in vivo. Because oxidative stress contributed to TSP1 DNA hypomethylation, early recognition of diabetic condition and timely administration of antioxidant are logical approaches to reduce complications associated with diabetes as alterations in epigenome may not be reversible by controlling glucose levels during the later stages of disease course. PMID- 26678679 TI - Assessment of Mutational Effects on Peptide Stability through Confinement Simulations. AB - The evaluation of free energy differences between specific states of a system is of fundamental interest in the study of (bio)chemical systems. Herein, we examine the use of the recently introduced confinement method (CM) to evaluate relative free energy changes upon protein/peptide mutations. CM is a path-independent technique that involves the transformation of a configurational state of the system into an ideal crystal permitting the direct computation of free energy differences. We illustrate the method by evaluating the differential stabilities between native and mutant sequences of a model peptide that has been extensively characterized by experimental approaches, the GB1 hairpin. We show a good correlation between calculated and experimental relative stabilities and discuss other possible applications of this method in the context of complex molecular conversions. PMID- 26678680 TI - Gibbs-Curie-Wulff Theorem in Organic Materials: A Case Study on the Relationship between Surface Energy and Crystal Growth. AB - The equilibrium crystal shape and shape evolution of organic crystals are found to follow the Gibbs-Curie-Wulff theorem. Organic crystals are grown by the physical vapor transport technique and exhibit exactly the same shape as predicted by the Gibbs-Curie-Wulff theorem under optimal conditions. This accordance provides concrete proof for the theorem. PMID- 26678682 TI - Strongyloides stercoralis: an unexpected cause of acute abdomen. PMID- 26678683 TI - Mechanical versus biological aortic valve replacement strategies. AB - Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology. PMID- 26678681 TI - The NeBoP score - a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe. AB - BACKGROUND: The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. METHOD: Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). RESULTS: The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). CONCLUSION: The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas. PMID- 26678684 TI - Improvements in sleep-related symptoms after endoscopic sinus surgery in patients with chronic rhinosinusitis. AB - BACKGROUND: Sleep impairment is highly prevalent in patients with chronic rhinosinusitis (CRS). Although endoscopic sinus surgery (ESS) has been shown to improve overall patient-reported sleep quality, the postoperative impact on individual sleep symptoms remains unclear. METHODS: Patients with medically recalcitrant CRS who elected to undergo ESS were prospectively enrolled into a multi-institutional, observational cohort study. Sleep-related symptom severity and treatment outcomes were assessed using the sleep domain questions within the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: A total of 334 participants met criteria and were followed postoperatively for an average of 14.5 +/- 4.9 months (mean +/- standard deviation [SD]). Mean SNOT-22 sleep domain scores improved from 13.7 +/- 6.8 to 7.7 +/- 6.6 (p < 0.001). Significant mean relative improvements were reported for "difficulty falling asleep" (45%; p < 0.001), "waking up at night" (40%; p < 0.001), "lack of a good night's sleep" (43%; p < 0.001), "waking up tired" (40%; p < 0.001), and "fatigue" (42%; p < 0.001) scores. A total of 66% of study participants reported postoperative improvement in "lack of a good night's sleep," "waking up tired," and "fatigue"; 62% reported improvement in "waking up at night"; and 58% reported improvement in "difficulty falling asleep." CONCLUSION: Patients with CRS report significant and sustained improvements following ESS in common sleep-related symptoms as assessed by the SNOT-22 sleep domain. Despite these significant improvements, some degree of persistent postoperative sleep impairment was reported. Further study is necessary to determine what factors are associated with continued sleep dysfunction after sinus surgery. PMID- 26678685 TI - Genetic and environmental impacts on DNA methylation levels in twins. AB - Epigenetics describes the study of cellular modifications that can modify the expression of genes without changing the DNA sequence. DNA methylation is one of the most stable and prevalent epigenetic mechanisms. Twin studies have been a valuable model for unraveling the genetic and epigenetic epidemiology of complex traits, and now offer a potential to dissect the factors that impact DNA methylation variability and its biomedical significance. The twin design specifically allows for the study of genetic, environmental and lifestyle factors, and their potential interactions, on epigenetic profiles. Furthermore, genetically identical twins offer a unique opportunity to assess nongenetic impacts on epigenetic profiles. Here, we summarize recent findings from twin studies of DNA methylation profiles across tissues, to define current knowledge regarding the genetic and nongenetic factors that influence epigenetic variation. PMID- 26678686 TI - Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus. AB - WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, no reports have been published on clinical outcomes of implementation of antimicrobial stewardship in patients receiving pathogen-specific antibiotics. METHOD: To evaluate the clinical outcomes of patients who received drugs, we conducted a single-centre, retrospective study of the effects of an antimicrobial stewardship programme targeting methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0.001) shortened, and the rate of de-escalation was significantly elevated (47.1% vs. 96.2%, P < 0.001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33.3% vs. 17.6%, P = 0.007) after intervention. WHAT IS NEW AND CONCLUSIONS: Daily review of administration of antimicrobials targeting MRSA was highly effective in improving clinical outcomes by optimizing early antimicrobial therapy. PMID- 26678687 TI - Dissection of the function of the RmpM periplasmic protein from Neisseria meningitidis. AB - RmpM is a periplasmic protein from Neisseria meningitidis that comprises an N terminal domain (residues 1-47) and a separate globular C-terminal domain (residues 65-219) responsible for binding to peptidoglycan. Here we show, through the use of size exclusion chromatography and pull-down assays, that a recombinant N-terminal fragment of RmpM binds to both the major outer membrane porins, PorA and PorB. Analysis by semi-native SDS-PAGE established that both recombinant full length RmpM and an N-terminal fragment, but not the C-terminal peptidoglycan binding domain, were sufficient to stabilize the PorA and PorB oligomeric complexes. Evidence from binding assays indicated that the meso-diaminopimelate moiety plays an important role in peptidoglycan recognition by RmpM. Site directed mutagenesis showed that two highly conserved residues, Asp120 and Arg135, play an important role in peptidoglycan binding. The yield of outer membrane vesicles, which have been used extensively as a vaccine against N. meningitidis, was considerably higher in an N. meningitidis strain expressing a truncated N-terminal fragment of RmpM (DeltaC-term rmpM) than in the WT strain. The native oligomeric state of the PorA/PorB complexes was maintained in this strain. We conclude that the dual functions of RmpM are independent, and that it is possible to use this knowledge to engineer a strain with higher yield of outer membrane vesicles, whilst preserving PorA and PorB, which are key protective antigens, in their native oligomeric state. PMID- 26678688 TI - Phytase-mediated mineral solubilization from cereals under in vitro gastric conditions. AB - BACKGROUND: Enzymatic dephosphorylation of phytic acid (inositol hexakisphosphate) in cereals may improve mineral bioavailability in humans. This study quantified enzymatic dephosphorylation of phytic acid by measuring inositol tri- to hexakisphosphate (InsP3-6) degradation and iron and zinc release during microbial phytase action on wheat bran, rice bran and sorghum under simulated gastric conditions. RESULTS: InsP3-6 was depleted within 15-30 min of incubation using an Aspergillus niger phytase or Escherichia coli phytase under simulated gastric conditions, with the two enzymes dephosphorylating cereal phytic acid at similar rates and to similar extents. Microbial phytase-catalyzed phytate dephosphorylation was accompanied by increased iron and zinc release from the cereal substrates. However, for wheat bran at pH 5, the endogenous wheat phytase activity produced mineral release equal to or better than that of the microbial phytases. No increases in soluble cadmium, lead or arsenic were observed with microbial phytase-catalyzed phytate dephosphorylation. CONCLUSION: Microbial phytase treatment abated phytate chelation hence enhanced the release of iron and zinc from phytate-rich cereals under simulated gastric conditions. The data infer that acid-stable microbial phytases can help improve iron bioavailability from phytate-rich cereal substrates via post-ingestion activity. (c) 2015 Society of Chemical Industry. PMID- 26678689 TI - Persistent groin pain after a bicycle fall. AB - Motor scooter handlebar syndrome (MSH) is uncommon. MSH includes groin pain associated with intimal injury to the common femoral artery caused by a direct blow from objects such as a motor scooter handlebar. We describe a case of a 23 year-old man with MSH occurring after a bicycle fall. The diagnosis was performed 5 years after the onset of pain. The patient underwent endovascular surgery and made a rapid recovery. Postoperatively, he was free of symptoms. This case highlights the difficulty of recognising this syndrome. PMID- 26678690 TI - Fatal thalamic abscess secondary to dental infection. AB - We present the case of poor neurological recovery and subsequent death secondary to a thalamic abscess in a 53-year-old man. This patient initially presented with sudden dysarthria and left hemiparesis while driving. Neuroimaging showed a multilobular abscess involving the right thalamus with oedema extending to the basal ganglionic region and brainstem. The source of the abscess was initially unknown and it required draining multiple times while the different causes were being explored. The patient's neurological state along with intubation made for a difficult and inconclusive oral examination. It was only after neuroimaging included tooth-bearing areas that it became evident that this patient had extensive periodontal disease with multiple areas of periapical radiolucencies. The patient underwent complete dental clearance alongside repeated drainage of the abscess. Despite initial postoperative improvement, the patient never recovered from the neurological damage and died 3 weeks later. PMID- 26678691 TI - Small intestine perforation due to accidental press-through package ingestion in an elderly patient with Lewy body dementia and recurrent cardiopulmonary arrest. AB - An octogenarian with Lewy body dementia presented to our hospital in cardiac arrest and was successfully resuscitated. Although he had abdominal pain the previous day, small bowel wall oedema and ascites were the only abnormalities noted on abdominal CT. Despite treatment with catecholamines and antimicrobials, he died of recurrent cardiopulmonary arrest later the same day. An autopsy showed that the patient's death was the result of a small bowel perforation caused by accidental ingestion of a press-through package (PTP). Precautions regarding PTP use and improved packaging design are necessary to prevent PTP ingestion, especially in elderly patients with dementia. PMID- 26678692 TI - Endobronchial actinomycosis: successful treatment with oral antibiotics. AB - This is a case report of an 84-year-old lady who presented with haemoptysis, weight loss and a right hilar mass on chest radiograph. CT scan of the chest revealed complete proximal occlusion of the right upper lobe from an endobronchial lesion consistent with a tumour. The patient was initially reluctant to undergo fibreoptic bronchoscopy as she was deemed to be unsuitable for any curative treatment of lung carcinoma. Bronchoscopy showed an exophytic necrotic tumour within the right upper lobe. Biopsies showed many bacterial colonies consistent with actinomyces and a diagnosis of endobronchial actinomycosis was made. Owing to multiple antibiotic allergies and patient refusal to have intravenous antibiotics, she was started on a course of doxycycline 200 mg once daily. There was near complete improvement in symptoms and radiographic appearances by the end of 4 months. This case highlights the importance of confirmatory diagnosis in the elderly as curable conditions are otherwise missed. PMID- 26678693 TI - Symptomatic unicuspid aortic valve. AB - A 22-year-old man with typical angina was seeking medical attention at primary health clinics for a couple of months. Owing to his young age and the absence of coronary artery disease risk factors, he was assured of no serious problem. Proper examination at a referral centre revealed weak peripheral pulses with diminished and delayed carotid upstroke. A normal S1 with a soft S2 were audible. A 3/6 late peaking systolic murmur was best heard in the aortic area radiating to the neck. Symptomatic bicuspid aortic valve disease was suspected. Diagnosis of unicuspid aortic valve was established by transoesophageal and three-dimensional echocardiography. The valve was successfully replaced with a mechanical prosthesis. The patient remains asymptomatic at 1 year follow-up. PMID- 26678694 TI - Ear and vestibular symptoms in train operators after sudden air pressure changes in trains. AB - A healthy 31-year-old train operator presented to our occupational health clinic reporting ear aches, headaches, dizziness, unsteadiness and even slight tinnitus. These symptoms first appeared when the patient started operating from a new train cabin. He described a sudden pressure gradient, experienced on some parts of the trajectory, which might have caused these problems. Although the cabins were equipped with a pressure equalising device, this was usually switched off because of the device creating an uncomfortable feeling in the cabin. The literature describes sudden pressure gradients as possible factors for passenger discomfort. PMID- 26678695 TI - Two cases of severe angio-oedema and rationale for their response to icatibant. PMID- 26678696 TI - Cervical spinal cord compression complicating the clinical course of Charcot Marie-Tooth type 1. PMID- 26678697 TI - Traumatic dislocation of the mandibular lateral incisor into the nasal floor. PMID- 26678698 TI - Cutaneous manifestations of Helicobacter cinaedi: a review. AB - Helicobacter cinaedi is an emerging Gram-negative spiral bacillus that was first reported in 1984. It has been implicated as a cause of gastroenteritis and bacteraemia in immunocompromised individuals. Helicobacter cinaedi-associated bacteraemia is sometimes accompanied by skin lesions; however, the cutaneous manifestations of this pathogen are not widely known. To our knowledge, a comprehensive review with detailed analysis of skin lesions associated with H. cinaedi has not been conducted. This article summarizes the clinical appearance of H. cinaedi cellulitis and its management. In addition, we conducted a retrospective review of 73 patients with H. cinaedi bacteraemia at a single institution, to further clarify the characteristic cutaneous features. It was found that 30% (22/73) of the cases of H. cinaedi bacteraemia had sudden-onset erythema accompanied by high fever. The most common cutaneous symptom of H. cinaedi bacteraemia was found to be mild cellulitis, appearing as multiple painful infiltrated erythemas on the extremities. As H. cinaedi is not always detectable in routine blood culture techniques, evaluation of these characteristic cutaneous manifestations seems important in diagnosis. Helicobacter cinaedi infection should be added to the diagnostic list of unspecified fever with painful infiltrated erythemas. PMID- 26678699 TI - Pressure-driven suppression of the Jahn-Teller effects and structural changes in cupric oxide. AB - Multiferroics have been of interest as materials for use in data storage due to their coexisting ferroelectric and ferromagnetic properties. The properties of cupric oxide have been studied at pressures below 70 GPa, and it has even been suggested that it may be a room temperature multiferroic at pressures of 20 to 40 GPa. However, the properties of cupric oxide above these pressures have yet to be thoroughly examined. Here, we investigate changes in the crystal structure of cupric oxide via first principles methods. We find that the crystal structure transforms from a monoclinic structure at low pressure to a face-centred cubic and body-centred cubic structure at high pressure. We also find that the magnetic ordering switches from antiferromagnetic in the monoclinic phase to net zero magnetic moment in the face-centred cubic phase and ferromagnetic in the body centred cubic phase. This shift in magnetic ordering is due to the superexchange interactions and Jahn-Teller instabilities, or the lack of thereof, arising from the d-orbital electrons of the cupric ions, which disrupt the mechanical stability of other possible magnetic orderings. PMID- 26678700 TI - Rapid Prototyping of a High Sensitivity Graphene Based Glucose Sensor Strip. AB - A rapid prototyping of an inexpensive, disposable graphene and copper nanocomposite sensor strip using polymeric flexible substrate for highly sensitive and selective nonenzymatic glucose detection has been developed and tested for direct oxidization of glucose. The CuNPs were electrochemically deposited on to the graphene sheets to improve electron transfer rates and to enhance electrocatalytic activity toward glucose. The graphene based electrode with CuNPs demonstrated a high degree of sensitivity (1101.3 +/- 56 MUA/mM.cm2), excellent selectivity (without an interference with Ascorbic Acid, Uric Acid, Dopamine, and Acetaminophen), good stability with a linear response to glucose ranging from 0.1 mM to 0.6 mM concentration, and detection limits of 0.025 mM to 0.9 mM. Characterization of the electrodes was performed by scanning electron microscopy (FESEM and SEM). The electrochemical properties of the modified graphene electrodes were inspected by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and amperometry. PMID- 26678701 TI - Designing More Efficient Preclinical Experiments: A Simulation Study in Chemotherapy-Induced Myelosupression. AB - A new more efficient preclinical study design (referred to as a compact design) is proposed that removes the need for satellite animals for the collection of toxicokinetic (TK) data by sampling from the main study animals, taking no more than one sample in 24 h to build up a full profile over the course of the study. The compact design's performance was tested with a simulation study, using an example of chemotherapy-induced myelosupression in rats. Data sets were simulated from a model based on available data, following both the compact design and a traditional design using satellite animals, with 100 studies being simulated for each. The effect of the compact design on parameter and variance estimates for the TK and neutrophil models were investigated, as well as the potential effect of interoccasion variability (IOV). The compact design performed equally as well as the traditional design, and had little impact on parameter or variation estimates, indicating that it would be a suitable alternative to traditional satellite designs while reducing the number of animals required. When IOV was present but not accounted for during the TK analysis some parameter estimates were biased and interindividual variation and residual errors inflated; this was reduced by allowing for IOV in the analysis. Using the compact design removes the need for a satellite group, reducing the number of animals required, without affecting the ability to model the data. If large IOV is suspected, caution should be exercised to avoid parameter estimation bias, and inflation of variability and residual error. PMID- 26678703 TI - Are self-management strategies effective in chronic pain treatment? AB - It has long been recognized that in the management of chronic illnesses generally, medical care alone is unlikely to be sufficient without the active contribution of the patient. This perspective has also been enunciated in numerous guidelines for the management of chronic pain. However, in the case of chronic pain at least, the nature and role of self-management have been poorly defined and, as a result, poorly understood and researched. This review considers the nature of self-management strategies for chronic pain, evidence of their effectiveness and ways in which self-management can be facilitated for those in chronic pain. A research and training agenda is proposed for where this work could go next. PMID- 26678702 TI - Acute Exposure to Di(2-Ethylhexyl) Phthalate in Adulthood Causes Adverse Reproductive Outcomes Later in Life and Accelerates Reproductive Aging in Female Mice. AB - Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant incorporated in consumer products. Studies have shown that DEHP targets the ovary to disrupt essential processes required for reproductive and nonreproductive health. Specifically, 10-day exposure to DEHP accelerates primordial follicle recruitment and disrupts estrous cyclicity in adult mice. However, it is unknown if these effects on folliculogenesis and cyclicity following acute DEHP exposure can have permanent effects on reproductive outcomes. Further, the premature depletion of primordial follicles can cause early reproductive senescence, and it is unknown if acute DEHP exposure accelerates reproductive aging. This study tested the hypothesis that acute DEHP exposure causes infertility, disrupts estrous cyclicity, alters hormone levels, and depletes follicle numbers by inducing atresia later in life, leading to accelerated reproductive aging. Adult CD-1 mice were orally dosed with vehicle or DEHP (20 MUg/kg/day-500 mg/kg/day) daily for 10 days, and reproductive outcomes were assessed at 6 and 9 months postdosing. Acute DEHP exposure significantly altered estrous cyclicity compared to controls at 6 and 9 months postdosing by increasing the percentage of days the mice were in estrus and metestrus/diestrus, respectively. DEHP also significantly decreased inhibin B levels compared to controls at 9 months postdosing. Further, DEHP significantly increased the BAX/BCL2 ratio in primordial follicles leading to a significant decrease in primordial and total follicle numbers compared to controls at 9 months postdosing. Collectively, the adverse effects present following acute DEHP exposure persist later in life and are consistent with accelerated reproductive aging. PMID- 26678704 TI - Joy Leads to Overconfidence, and a Simple Countermeasure. AB - Overconfidence has been identified as a source of suboptimal decision making in many real-life domains, with often far-reaching consequences. This study identifies a mechanism that can cause overconfidence and demonstrates a simple, effective countermeasure in an incentive-compatible experimental study. We observed that joy induced overconfidence if the reason for joy (an unexpected gift) was unrelated to the judgment task and if participants were not made specifically aware of this mood manipulation. In contrast, we observed well calibrated judgments among participants in a control group who were in their resting mood. Furthermore, we found well-calibrated judgments among participants who received the joyful mood induction together with questions that forced them to reflect on their current mood and the (ir)relevance of its cause to our judgment tasks. Our findings suggest that being aware of one's positive mood and the reason for that mood may effectively reduce overconfidence for a short period. PMID- 26678705 TI - [Formula: see text]Cognitive and behavioral rating measures of executive function as predictors of academic outcomes in children. AB - Interrelations of two measurement methods (cognitive versus behavioral ratings) for executive function (EF) were examined and related to reading comprehension and math calculations in fourth and fifth grade students (n = 93) in the context of a diverse urban student population. Relations among measures within four EF processes (working memory, planning, inhibition and shifting) were modest; relations to academics were stronger. EF measures contributed to both academic outcomes even in the context of relevant covariates (age, language and educational program). Working memory was particularly important for reading comprehension across measurement type. Cognitive measures from all EF processes, particularly inhibition and planning, and behavioral ratings of working memory were important for math. PMID- 26678706 TI - Individualized covariance profile of cortical morphology for auditory hallucinations in first-episode psychosis. AB - Neocortical phenotype of cortical surface area (CSA) and thickness (CT) are influenced by distinctive genetic factors and undergo differential developmental trajectories, which could be captured using the individualized cortical structural covariance (ISC). Disturbed patterns of neocortical development and maturation underlie the perceptual disturbance of psychosis including auditory hallucination (AH). To demonstrate the utility of selected ISC features as primal biomarker of AH in first-episode psychosis (FEP) subjects experiencing AH (FEP AH), we employed herein a support vector machine (SVM). A total of 147 subjects (FEP-AH, n = 27; FEP-NAH, n = 24; HC, n = 96) underwent T1 -weighted magnetic resonance imaging at 3T. The FreeSurfer software suite was used for cortical parcellation, with the CSA-ISC and CT-ISC then calculated. The most informative ISCs showing statistical significance (P < 0.001) across every run of leave-one out group-comparison were aligned according to the absolute value of averaged t statistics and were packaged into candidate feature sets for classification analysis using the SVM. An optimal feature set comprising three CSA-ISCs, including the intraparietal sulcus, Broca's complex, and the anterior insula, distinguished FEP-AH from FEP-NAH subjects with 83.6% accuracy (sensitivity = 82.8%; specificity = 85.7%). Furthermore, six CT-ISCs encompassing the executive control network and Wernicke's module classified FEP-AH from FEP-NAH subjects with 82.3% accuracy (sensitivity = 79.5%; specificity = 88.6%). Finally, extended sets of ISCs related to the default-mode network distinguished FEP-AH or FEP-NAH from HC subjects with 89.0-93.0% accuracy (sensitivity = 88.4-93.4%; specificity = 89.0-94.1%). This study established a distinctive intermediate phenotype of biological proneness for AH in FEP using CSA-ISCs as well as a state marker of disease progression using CT-ISCs. PMID- 26678707 TI - Novel Raman Spectroscopic Biomarkers Indicate That Postyield Damage Denatures Bone's Collagen. AB - Raman spectroscopy has become a powerful tool in the assessment of bone quality. However, the use of Raman spectroscopy to assess collagen quality in bone is less established than mineral quality. Because postyield mechanical properties of bone are mostly determined by collagen rather than the mineral phase, it is essential to identify new spectroscopic biomarkers that help infer the status of collagen quality. Amide I and amide III bands are uniquely useful for collagen conformational analysis. Thus, the first aim of this work was to identify the regions of amide bands that are sensitive to thermally induced denaturation. Collagen sheets and bone were thermally denatured to identify spectral measures that change significantly following denaturation. The second aim was to assess whether mechanical damage denatures the collagen phase of bone, as reflected by the molecular spectroscopic biomarkers identified in the first aim. The third aim was to assess the correlation between these new spectroscopic biomarkers and postyield mechanical properties of cortical bone. Our results revealed five peaks whose intensities were sensitive to thermal and mechanical denaturation: ~1245, ~1270, and ~1320 cm(-1) in the amide III band, and ~1640 and ~1670 cm(-1) in the amide I band. Four peak intensity ratios derived from these peaks were found to be sensitive to denaturation: 1670/1640, 1320/1454, 1245/1270, and 1245/1454. Among these four spectral biomarkers, only 1670/1640 displayed significant correlation with all postyield mechanical properties. The overall results showed that these peak intensity ratios can be used as novel spectroscopic biomarkers to assess collagen quality and integrity. The changes in these ratios with denaturation may reflect alterations in the collagen secondary structure, specifically a transition from ordered to less-ordered structure. The overall results clearly demonstrate that this new spectral information, specifically the ratio of 1670/1640, can be used to understand the involvement of collagen quality in the fragility of bone. (c) 2015 American Society for Bone and Mineral Research. PMID- 26678708 TI - Antiplatelet Treatment Reduces All-Cause Mortality in COPD Patients: A Systematic Review and Meta-Analysis. AB - Previous studies clearly showed that patients with chronic obstructive pulmonary disease (COPD) are at high risk for cardiovascular events. Platelet activation is significantly heightened in these patients, probably because of a chronic inflammatory status. Nevertheless, it is unclear whether antiplatelet treatment may contribute to reduce all-cause mortality in COPD patients. To clarify this issue, we performed a systematic review and meta-analysis including patients with COPD (outpatients or admitted to hospital for acute exacerbation). The primary endpoint was all-cause mortality. We considered studies stratifying the study population according the administration or not of antiplatelet therapy and reporting its relationship with the primary endpoint. Overall, 5 studies including 11117 COPD patients were considered (of those 3069 patients were with acute exacerbation of COPD). IHD was present in 33% of COPD patients [95%CI 31% 35%). Antiplatelet therapy administration was common (47%, 95%CI 46%-48%), ranging from 26% to 61%. Of note, IHD was considered as confounding factor at multivariable analysis in all studies. All-cause mortality was significantly lower in COPD patients receiving antiplatelet treatment (OR 0.81; 95%CI 0.75 0.88). The data was consistent both in outpatients and in those with acute exacerbation of COPD. The pooled studies analysis showed a very low heterogeneity (I(2) : 8%). Additional analyses (meta-regression) showed that antiplatelet therapy administration was effective independently (to potential confounding factors as IHD, cardiovascular drugs and cardiovascular risk factors. In conclusion, our meta-analysis suggested that antiplatelet therapy might significantly contribute to reduce all-cause mortality in COPD patients. PMID- 26678709 TI - Microfluidic Diffusion Analysis of the Sizes and Interactions of Proteins under Native Solution Conditions. AB - Characterizing the sizes and interactions of macromolecules under native conditions is a challenging problem in many areas of molecular sciences, which fundamentally arises from the polydisperse nature of biomolecular mixtures. Here, we describe a microfluidic platform for diffusional sizing based on monitoring micron-scale mass transport simultaneously in space and time. We show that the global analysis of such combined space-time data enables the hydrodynamic radii of individual species within mixtures to be determined directly by deconvoluting average signals into the contributions from the individual species. We demonstrate that the ability to perform rapid noninvasive sizing allows this method to be used to characterize interactions between biomolecules under native conditions. We illustrate the potential of the technique by implementing a single step quantitative immunoassay that operates on a time scale of seconds and detects specific interactions between biomolecules within complex mixtures. PMID- 26678710 TI - The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial. AB - BACKGROUND: Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. METHODS: A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. RESULTS: Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16 18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean +/- standard deviation temperature was 37.4+/-0.5 degrees C in the paracetamol group and 37.7+/-0.4 degrees C in the saline group (absolute difference -0.3 degrees C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. CONCLUSION: The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000444280. PMID- 26678711 TI - Liver Resident Macrophages (Kupffer Cells) Share Several Functional Antigens in Common with Endothelial Cells. AB - The identification and specific functions of Kupffer cells (KCs), a liver resident macrophage subpopulation, are still unclear. We compared KCs with peritoneal macrophages using cDNA microarray analysis and found that these cells share some antigens with endothelial cells. KCs highly express VCAM-1 and VEGF receptors (VEGF-Rs) at transcriptional and protein levels. VCAM-1 mediates the functional binding of KCs with lymphocytes and induces KC activation. Among the VEGF receptors, VEGF-R2 and VEGF-R3 were expressed on the KCs, while VEGF-R1 was expressed on other tissue macrophage subsets. VEGF120, a ligand of both VEGF-R1 and VEGF-R2, transduced strong survival and chemotactic signals through the KCs, when compared to PIGF, a VEGF-R1 ligand, indicating that VEGF-R2 plays significant roles in regulating KC activities. Expression of the VEGF-Rs was regulated by TLR4 signalling. These results suggest that the function of KCs is partly regulated by the common antigens shared with endothelial cells. PMID- 26678712 TI - Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds. AB - Inhibition of cyclooxygenase (Cox) enzymatic activity by non-steroidal anti inflammatory drugs (NSAIDs) provides the molecular basis of analgesia following wounding or surgery. This study investigated the role of Cox activity in the regulation of vascular endothelial growth factor (VEGF) expression in keratinocytes and the formation of new blood vessels in acute wounds in mice. To this end, human HaCaT keratinocytes were stimulated with epidermal growth factor (EGF). EGF increased Cox-1 mRNA in the presence of the constitutively expressed Cox-1 protein in keratinocytes. EGF coinduced Cox-2 and VEGF165 mRNA and protein expression and an accumulation of prostaglandin E2 (PGE2 ) in cell culture supernatants. Inhibition of Cox isozyme activity by Cox-1 and -2 siRNA or ibuprofen reduced PGE2 and VEGF165 release from keratinocytes. In a mouse model of excisional wound healing, Cox-2 and VEGF165 expression were colocalized in the granulation tissue of acute wounds. Oral treatment of mice with the Cox-1 and -2 inhibitor diclofenac was associated with reduced levels of VEGF165 protein and an impaired blood vessel formation in acute wound tissue. In summary, our data suggest that a reduction of PGE2 -triggered VEGF165 protein expression in wound keratinocytes is likely to contribute to the observed impairment of wound neovascularisation upon Cox inhibition. PMID- 26678714 TI - Spontaneous Resolution of Evans-Showell-Type Polyoxometalates in Constructing Chiral Inorganic-Organic Hybrid Architectures. AB - Six new hybrid compounds based on [Co2Mo10H4O38](6-) polyoxoanion, (4 H2pya)6Co2Mo10H4O38.10H2O 1 (4-Hpya =3-(4-pyridyl)acrylic acid) and (4 H2pya)4[M(H2O)6][Co2Mo10H4O38].5H2O (M = Co 2, Ni 3, Cu 4, Zn 5, Cd 6), were synthesized and characterized by elemental analysis, IR spectroscopy, TG analysis, solid diffuse reflective spectrum, powder X-ray diffraction, and single crystal X-ray diffraction. Compound 1 crystallizes in the centrosymmetric space group P-1, which is built up of protonated 4-H2pya molecules and isolated [Co2Mo10H4O38](6-) polyoxoanions. Isostructural compounds 2-6 crystallize in the chiral space group P1 by spontaneous resolution, as a conglomerate of two enantiomerically pure crystals, which were obtained by adding different metal cations to the reaction system of compound 1. The structures of 2-6 comprise chiral [Co2Mo10H4O38](6-) anions, cationic [M(H2O)6](2+) units, and protonated 4 H2pya ligands. The chiral [Co2Mo10H4O38](6-) polyoxoanions can be connected up together by directional hydrogen-bonding interactions among terminal oxygen atoms of anions, coordinated water molecules and organic ligands to construct a 3D supramolecular chiral framework in 2-6. The absolute configuration of 2-6 was determined from the Flack parameter by X-ray crystallography and solid state circular dichroism spectroscopy. As far as we know, compounds 2-6 represent the first examples of chiral inroganic-organic hybrid species based on Evans-Showell type polyoxometalates. Furthermore, the second harmonic generation (SHG) activities for 2 and 4 were measured, showing an SHG efficiency of approximately 0.9 * KH2PO4. PMID- 26678713 TI - Dynamics of circulating tumor DNA represented by the activating and resistant mutations in epidermal growth factor receptor tyrosine kinase inhibitor treatment. AB - Circulating tumor DNA (ctDNA) is an emerging field of cancer research. For lung cancer, non-invasive genotyping of EGFR is the foremost application. The activating mutations represent the ctDNA from all cancer cells, and the T790M resistant mutation represents that from resistant cells. We examined the ctDNA dynamics of EGFR mutations by using deep sequencing with a massively parallel DNA sequencer. We obtained 190 plasma samples from 57 patients at various times during the treatment course and classified them according to treatment status. The mutation detection rate of exon 19 deletion/L858R in plasma was high at the initiation of treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI; P = 0.001), suppressed during EGFR-TKI treatment before disease progression, and elevated after the onset of disease progression (P = 0.023). The mutation detection rate of T790M was low until the onset of disease progression and elevated thereafter (P = 0.01). Samples across the development of disease progression were obtained from 10 patients and showed a correlation between increased ctDNA level and disease progression. Decreased ctDNA level in response to the initiation of EGFR-TKI was observed in 4 of 6 eligible patients. In two patients, the ctDNA dynamics suggested the presence of cancer cell populations only with the T790M mutation. In another patient, the T790M ctDNA represented cell subpopulations that respond to cytotoxic agents differently from the major population. Considering the high incidence, ctDNA could be a clinical parameter to complement information from image analyses. PMID- 26678716 TI - [In Process Citation]. AB - Since the 1950s, oxidised regenerate cellulose (TABOTAMP (r)) has been successfully applied for local haemostasis in intra- or postoperative bleeding complications. The scope of this medical product is large and it has found its place in oral and maxillofacial surgery. Although the application of TABOTAMP (r) in medicine and dentistry is common, further complications next to the absence of the haemostatic effect may be encountered if used incorrectly. The aim of this article is an update on the proper use of TABOTAMP (r). Further, tips are provided for the indication-specific application of this useful agent in clinical practice. PMID- 26678715 TI - The complete mitochondrial genome of the small-toothed forest hedgehog Mesechinus miodon (Eulipotyphla: Erinaceidae). AB - The complete mitochondrial genome of the small-toothed forest hedgehog Mesechinus miodon (Eulipotyphla: Erinaceidae) has been reconstructed from Illumina sequencing data. The circular genome is 16 842 bp long, comprising 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), and one control region. All PCGs are initiated with ATR (ATA/ATG) codons, except for nad4 with GTG as its initiation codon. Two PCGs (cox3 and nad4) harbor an incomplete termination codon T, while the others are terminated with TAA (atp6, cox1, cox2, nad1, nad2, nad3, nad4l, nad5, and nad6), TAG (atp8) or AGA (cytb). The base composition is highly biased (34.9% A, 19.7% C, 11.9% G, and 33.5% T for the light strand) with an overall A + T content of 68.4%. Phylogenetic analysis indicated that M. miodon is more closely related to the consubfamilial long-eared hedgehog Hemiechinus auritus than to those within the order Eulipotyphla. PMID- 26678717 TI - Effectiveness of neuromuscular taping on painful hemiplegic shoulder: a randomised clinical trial. AB - PURPOSE: The purpose of this trial was to investigate changes in pain, the range of motion (ROM) and spasticity in people with painful hemiplegic shoulder (PHS) after the application of an upper limb neuromuscular taping (NMT). METHODS: We conducted a randomised clinical trial. The study included 32 people, 31% female (mean +/- SD age: 66 +/- 9 years), with PHS after stroke with pain at rest and during functional movements. The experimental group received the application of NMT and a standard physical therapy programme (SPTP), whereas the control group received SPTP. The groups received four 45-minute long sessions over four weeks. The VAS, ROM and spasticity were assessed before and after the intervention with follow-up at four weeks. RESULTS: The experimental group had a greater reduction in pain compared to the control group at the end of the intervention, as well as at one month after the intervention (p < 0.001; all the group differences were greater than 4.5 cm, which is greater than the minimal clinically important difference of 2.0 cm). The experimental group had a significantly higher (i.e. better) ROM, by 30.0 degrees , than the control group in shoulder flexion (95% CI: 37.3-22.7) at 4 weeks and by 24.8 degrees (95% CI: 32.1-17.6) at 8 weeks as well as in abduction by 30.6 degrees (95% CI: 37.5-23.7) at 4 weeks and 25.1 degrees (95% CI: 33.8-16.3) at 8 weeks. CONCLUSION: Our study demonstrates that NMT decreases pain and increases the ROM in subjects with shoulder pain after a stroke. Implications for Rehabilitation Painful hemiplegic shoulder is a frequent complication after stroke with negative impacts on functional activities and on quality of life of people, moreover restricts rehabilitation intervention. Neuromuscular taping is a technique introduced by David Blow for the treatment of neuromuscoloskeletal problems. This study shows the reduction of pain and the improvement of range of motion after the application of an upper limb neuromuscular taping. Rehabilitation professionals who are involved in the management of painful hemiplegic shoulder may like to consider the benefits that neuromuscular taping can produce on upper limb. PMID- 26678718 TI - Using positron emission tomography (PET) response criteria in solid tumours (PERCIST) 1.0 for evaluation of 2'-deoxy-2'-[18F] fluoro-D-glucose-PET/CT scans to predict survival early during treatment of locally advanced non-small cell lung cancer (NSCLC). AB - INTRODUCTION: The demand for early-response evaluation with 2'-deoxy-2'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body CT (PET/CT) is rapidly growing. This study was initiated to evaluate the applicability of the PET response criteria in solid tumours (PERCIST 1.0) for response evaluation. METHODS: We performed a retrospective study of 21 patients with locally advanced non-small cell lung cancer (NSCLC), who had undergone both a baseline and a follow-up F-18-FDG-PET/CT scan during their treatments. The scans were performed at our institution in the period September 2009 and March 2011 and were analysed visually and according to PERCIST 1.0 by one board certified nuclear medicine physician. The response was compared with overall survival (OS) and progression-free survival (PFS). The variation in key parameters affecting the F-18-FDG uptake was assessed. RESULTS: A kappa of 0.94 corresponding to an almost perfect agreement was found for the comparison of the visual evaluation with PERCIST. Patients with partial metabolic response and stable metabolic disease (as evaluated by PERCIST 1.0) had statistically significant longer median time to progression: 8.4 months (confidence interval (CI) 5.1-11.8 months) as compared with 2.7 months (CI 0-5.6 months) in patients classified with progression. The variation in uptake time between baseline and follow-up scans was more than the recommended 15 min in 48% of patients. CONCLUSIONS: PERCIST 1.0 is readily implementable and highly comparable with visual evaluation of response using early F-18-FDG-PET/CT scanning for locally advanced NSCLC patients. In spite of variations in parameters affecting F-18-FDG uptake, evaluation of F-18-FDG-PET/CT during treatment with PERCIST 1.0 is shown to separate non-responders from responders, each with statistically significant differences in both OS and PFS. PMID- 26678719 TI - Unification of ground-state aromaticity criteria - structure, electron delocalization, and energy - in light of the quantum chemical topology. AB - In the present account we investigate a theoretical link between the bond length, electron sharing, and bond energy within the context of quantum chemical topology theories. The aromatic stabilization energy, ASE, was estimated from this theoretical link without using isodesmic reactions for the first time. The ASE values obtained from our method show a meaningful correlation with the number of electrons contributing to the aromaticity. This theoretical link demonstrates that structural, electronic, and energetic criteria of aromaticity - ground-state aromaticity - belong to the same class and guarantees that they assess the same property as aromaticity. Theory suggests that interatomic exchange-correlation potential, obtained from the theory of Interacting Quantum Atoms (IQA), is linearly connected to the delocalization index of Quantum Theory of Atoms in Molecules (QTAIM) and the bond length through a first order approximation. Our study shows that the relationship between energy, structure and electron sharing marginally deviates from the ideal linear form expected from the first order approximation. The observed deviation from linearity was attributed to a different contribution of exchange-correlation to the bond energy for the sigma- and pi-frameworks. Finally, we proposed two-dimensional energy-structure-based aromaticity indices in analogy to the electron sharing indices of aromaticity. PMID- 26678720 TI - Ultra High Dilution--Physiology and Physics comes of age. PMID- 26678721 TI - "Ultra High Dilution 1994" revisited 2015--the state of follow-up research. AB - BACKGROUND: The "Ultra High Dilution 1994" project was an endeavour to take stock of the findings and theories on homeopathic extreme dilutions that were under research at the time in areas of biology, biophysics, physics and medicine. The project finally materialized into an anthology assembling contributions of leading scientists in the field. Over the following two decades, it became widely quoted within the homeopathic community and also known in other research communities. The aim of the present project was to re-visit and review the 1994 studies from the perspective of 2015. METHOD: The original authors from 1994 or close laboratory colleagues were asked to contribute papers covering their research efforts and learnings in the period from 1994 up to 2015. These contributions were edited and cross-referenced, and a selection of further contributions was added. RESULTS: About a dozen contributions reported on follow up experiments and studies, including further developments in theory. Only few of the models that had seemed promising in 1994 had not been followed up later. Most models presented in the original publication had meanwhile been submitted to intra-laboratory, multicentre or independent scrutiny. The results of the follow up research seemed to have rewarded the efforts. Furthermore, contributions were provided on new models that had been inspired by the original ones or that may be candidates for further in-depth ultra high dilution (UHD) research. CONCLUSION: The project "Ultra High Dilution 1994 revisited 2015" is the latest output of what might be considered the "buena vista social club" of homeopathy research. However, it presents new developments and results of the older, established experimental models as well as a general survey of the state of UHD research. PMID- 26678722 TI - Update on hormesis and its relation to homeopathy. AB - INTRODUCTION: Hormesis is a dose-response relationship characterized by a biphasic dose response to stressors with a low dose stimulation and a high dose inhibition. The first systematic description of hormesis appeared toward the close of the 18th century by the German pharmacology professor Hugo Schulz. The stressor agent can be any agent or factor capable of causing a deleterious effect. The biological systems can be diverse: bacteria, fungi, algae, yeasts, animals, humans, protozoa and plants. The range of endpoints covers longevity, reproduction, cancer, survival, growth, metabolic effects and others. Hormesis is a nonspecific phenomenon, which can occur in any biological system and can be caused by any stressor. It is quantifiable and reproducible. The apparent similarity between the basic principle of hormesis and homeopathy's Similia Principle, together with the homeopathic claim that hormesis validates homeopathy caused its marginalization, and its rejection during the past century by central figures in pharmacology. Recent years have seen a slight renaissance in the conventional scientific attitude towards hormesis. METHOD: We compared hormesis and homeopathy. RESULT: There is no convincing evidence of similarity between these two systems. Moreover, there are several crucial differences between them, which seem to refute any idea that they stem from the same root. This paper discusses these differences. The rejection of hormesis on grounds of its similarity to homeopathy is unjustified. CONCLUSION: The authors suggest exploring the differences between both systems. Such exploration may answer the key question of whether they do indeed share a root or embrace the same principles. Such exploration may also spur research within both systems to answer further open questions. PMID- 26678723 TI - Replications of fundamental research models in ultra high dilutions 1994 and 2015 -update on a bibliometric study. AB - INTRODUCTION: This paper focuses exclusively on experimental models with ultra high dilutions (i.e. beyond 10(-23)) that have been submitted to replication scrutiny. It updates previous surveys, considers suggestions made by the research community and compares the state of replication in 1994 with that in 2015. METHODS: Following literature research, biochemical, immunological, botanical, cell biological and zoological studies on ultra high dilutions (potencies) were included. Reports were grouped into initial studies, laboratory-internal, multicentre and external replications. Repetition could yield either comparable, or zero, or opposite results. The null-hypothesis was that test and control groups would not be distinguishable (zero effect). RESULTS: A total of 126 studies were found. From these, 28 were initial studies. When all 98 replicative studies were considered, 70.4% (i.e. 69) reported a result comparable to that of the initial study, 20.4% (20) zero effect and 9.2% (9) an opposite result. Both for the studies until 1994 and the studies 1995-2015 the null-hypothesis (dominance of zero results) should be rejected. Furthermore, the odds of finding a comparable result are generally higher than of finding an opposite result. Although this is true for all three types of replication studies, the fraction of comparable studies diminishes from laboratory-internal (total 82.9%) to multicentre (total 75%) to external (total 48.3%), while the fraction of opposite results was 4.9%, 10.7% and 13.8%. Furthermore, it became obvious that the probability of an external replication producing comparable results is bigger for models that had already been further scrutinized by the initial researchers. CONCLUSIONS: We found 28 experimental models which underwent replication. In total, 24 models were replicated with comparable results, 12 models with zero effect, and 6 models with opposite results. Five models were externally reproduced with comparable results. We encourage further replications of studies in order to learn more about the model systems used. PMID- 26678724 TI - Wheat and ultra high diluted silver nitrate--further experiments and re-analysis of data. AB - BACKGROUND: Since 1926, an influence of a dilution of silver nitrate (24x) on the growth of coleoptiles of wheat seedlings was described. The aim of the study discussed here is the critical proof of the reliability of a test system which has been quoted as a basic model for the research on homoeopathy for decades. METHODS: Grains of winter wheat (Triticum aestivum) were observed under the influence of extremely diluted silver nitrate (10(-23)) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy ('24x'). Analogously prepared water and/or inert water was used for control. Thirty experiments including 5000+5000 grains were performed by 5 researchers. RESULTS: Stalk lengths clearly indicate that development is enhanced by the probe silver nitrate 24x as compared to control. When the experiments 1989-1995 were pooled, means and SD for silver nitrate 24x-groups were 42.3+/-26.9 mm and for water control groups 34.7+/-22.2 mm. Verum stalk length was 21.9% bigger than control (100%) (p<0.01; d=0.31, i.e. small). For the experiments 1998-2014, means and SD were 73.7+/-21.7 mm and 60.5+/-20.9 mm. Verum stalk length was 21.7% bigger than control (100%) (p<0.01; d=0.62, i.e. medium). From the results one may hypothesize that the result is more marked in experiments showing an average mean of stalk length between ca. 50 and 90 mm in contrast to smaller or bigger mean lengths. CONCLUSION: The previous findings were confirmed by the results. PMID- 26678725 TI - Amphibians and ultra high diluted thyroxine--further experiments and re-analysis of data. AB - BACKGROUND: A model of thyroxine and metamorphosis of highland amphibians is frequently mentioned as an example of experiments on extremely diluted substances in discussions around 'homeopathy'. METHODS: The model was scrutinized by reanalysing the results of the initial researcher A and a second researcher B as well as of 5 external researchers C between 1990 and 2013. Rana temporaria larvae were taken from an alpine highland biotope. The test solution was thyroxine 10( 30) (T30x), tetra-iodo-thyronine sodium pentahydrate diluted with pure water in 26 steps of 1:10, being agitated after each step. Analogously prepared water (W30x) was used for control. Tadpoles were observed from the 2-legged to the 4 legged stage. Experiments were performed in different years, at different times of season, and their duration could vary. Frequencies of 4-legged animals, effect sizes and areas under the curves (AUCs) were calculated and regression analyses were performed to investigate possible correlations between year, season, duration etc. Experiments were in line with animal protection guidelines. RESULTS: The total set of data A + B + C as well as subsets A (initial researcher, N=286+293), B (second centre, 965 + 965) and C (5 external researchers, 690 + 690) showed an effect of extremely diluted agitated thyroxine reverse to that known of molecular thyroxin, i.e. test values were below control by 11.4% for A, 9.5% for B and 7.0% for C (p<0.001 for each of the subsets). The effect size (Cohen's d) was >0.8 (large) for both A and B and 0.74 (medium) for C. CONCLUSION: Although a perfect reproducibility was not obtained, this paradoxical phenomenon was generally consistent in different observations. Correlations were found between details of laboratory handling, as well as environment temperature, and the size of the results. PMID- 26678726 TI - Wheat and ultra high diluted gibberellic acid--further experiments and re analysis of data. AB - BACKGROUND: Following studies (a) on wheat seedlings and ultra high diluted silver nitrate, and (b) on amphibians and an ultra high diluted hormone, (c) a bio-assay on wheat and extremely diluted gibberellic acid was standardized. This assay was intended to combine the easy-to-handle aspect of (a) and biologically interesting aspects of (b). The purpose of the data analysis presented here was to investigate the influence of an extreme dilution of gibberellic acid on wheat stalk length and to determine the influence of external factors on the experimental outcome. METHODS: Grains of winter wheat (Triticum aestivum, Capo variety) were observed under the influence of extremely diluted gibberellic acid (10(-30)) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy ('G30x'). Analogously prepared water was used for control ('W30x'). 16 experiments including 8000+8000 grains were performed by 9 researchers. RESULTS: Experiments that were performed between January and April showed inconsistent results, whereas most of the experiments performed between September and December showed shorter stalks in the G30x group. This was confirmed by correlation analysis (p<0.01). Thus winter/spring experiments and autumn experiments were analysed separately. When all 10 autumn experiments were pooled, mean stalk lengths (mm) were 48.3+/-21.4 for the verum group and 52.1+/ 20.4 for control (mean+/-SD) at grain level (N=5000 per group) and +/-5.3 and +/ 5.1 respectively at dish level. In other words, verum stalk length (92.67%) was 7.33% smaller than control stalk length (100%). The effect size is small when calculation is done on the basis of grains (d=0.18) but, due to the smaller SD at dish level, medium when done on the basis of dishes (d=0.73). The inhibiting effect was observed by 6 of the 6 researchers who performed the autumn experiments. CONCLUSION: The model may be useful for further research as there exists a theoretical justification due to previous studies with wheat and extremely diluted silver nitrate, as well as to previous studies with amphibians and diluted hormones, and its methods are well standardized. Data confirm the hypothesis that information can be stored in the test liquid, even at a dilution of the original substance beyond Avogadro's value; and that the wheat bio-assay is sensitive to such information. PMID- 26678727 TI - Immunological models in high dilution research following M Bastide. AB - In 1994, Madeleine Bastide described experimental models in immunology that were used during the 1980s to investigate high dilution effects on several biological systems. She classified the available papers in four categories: High dilutions of antigens; High dilutions of thymus, bursa and other hormones; High dilutions of cytokines; Immunopharmacological activity of silica. The studies about high dilutions of antigens were not continued after this period, but gave rise to a long process of a series of in vitro models on antigens and histamine dilutions, that led to the demonstration of the biological modulation effects of these preparations on basophil degranulation. During this process, a multi-centre study was performed, with a high degree of reproducibility among different independent laboratories. The studies about high diluted cytokines, thymulin and other hormones opened a new line of scientific investigation, about the regulatory properties of endogenous substances prepared according to homeopathic methods. The most frequently studied substance, thymulin, when administered to mice at 5cH potency, is able to improve the activity of phagocytes in different experimental situations, such as viral, bacterial and parasitic infections. The immunopharmacological activity of silica was demonstrated, at that time, as an in vivo illustration of the homeopathic 'similia principle'. More recently, studies on silica have assumed another focus: the putative role of silica as active contaminant present in high dilutions. This paper presents a follow-up summary on these items, considering the evolution of discoveries from 1994 to 2014. PMID- 26678728 TI - Survey of immuno-allergological ultra high dilution research. AB - BACKGROUND: Experiments about basic research in Immuno-allergology reported by M. Bastide and B. Poitevin in Ultra High Dilution (1994) have been appraised from a 20 year perspective. The numerous experiments published mainly focus on immunological regulation, inflammatory process and basophil activation. They are analyzed according to one essential criterion: repeatability. METHODS: The commentary reflects the research details made available in a recently published literature review, also published in French. RESULTS: The regulatory effect of high dilution of bursin on immune response has been observed in multiple experiments but not reproduced by independent teams. The immunomodulating effect of Thymulin has been confirmed in mice. Rhus toxicodendron has an anti inflammatory activity on different models, from mother tincture (TM) to very high dilutions. The homeopathic complex Canova activates macrophages in vitro and in vivo, induces lymphocyte proliferation, and reduces the size of tumors and mortality of sarcoma-bearing mice. Some homeopathic medicines used in clinical inflammation modulate in vitro the neutrophil activation, with variability in the protocols used and in the medicines tested. In allergology, high dilution histamine has an inhibitory effect on basophil activation in multicenter trials and with independent teams, either with methods implying a change in basophil staining or with flow cytometry. However, high dilution histamine had no effect in some well-conducted experiments. The inhibitory effect of Apis mellifica has not been studied with the flow cytometry method, as well as the activation of basophil by anti-IgE high dilution, published in Nature. CONCLUSIONS: Despite considerable research activity in immuno-allergology and a great increase in the number of publications, there is still not in this domain a "gold standard" trial in basic research in homeopathy. The most studied system, the inhibitory effect of histamine high dilutions on basophil activation, requires clarifications of various factors, including individual sensitivity. For scientific and epistemological reasons, the same work should be carried out for independent reproduction of the experiments conducted with anti-IgE and Apis mel high dilution, in complement of the new axes of research in immunoallergology developed since 20 years. PMID- 26678729 TI - The use of plant-based bioassays in homeopathic basic research. AB - OBJECTIVES: The objective was to evaluate homeopathic basic research studies that use plant-based bioassays. With this in view, a compilation was made of the findings of three systematic literature reviews covering plant-based bioassays in the three fields of healthy, abiotically, or biotically stressed plants. This compilation focused on investigations using advanced experimental methods and detailed descriptions, also with the aim of supporting the design of future experiments. METHODS: Publications included had to report on studies into the effects of homeopathic preparations on whole plants, seeds, plant parts and cells. Outcomes had to be measured by established procedures and statistically evaluated. A Manuscript Information Score (MIS) was applied using predefined criteria to identify publications with sufficient information for adequate interpretation (MIS >= 5). Additional evaluation focused on the use of adequate controls to investigate specific effects of homeopathic preparations, and on the use of systematic negative control (SNC) experiments to ensure the stability of the bioassay. Only a fraction of the studies reported here were performed with 'ultra high' dilutions, whereas other studies were performed with moderate or high dilutions. RESULTS: A total of 157 publications were identified, describing a total of 167 experimental studies. 84 studies included statistics and 48 had a MIS >= 5, thus allowing adequate interpretation. 29 studies had adequate controls to identify specific effects of homeopathic preparations, and reported significant effects of decimal and centesimal homeopathic potencies, including dilution levels beyond Avogadro's number. 10 studies reported use of SNC experiments, yielding evidence for the stability of the experimental set-up. CONCLUSION: Plant models appear to be a useful approach for investigating basic research questions relating to homeopathic preparations, but more independent replication trials are needed in order to verify the results found in single experiments. Adequate controls and SNC experiments should be implemented on a routine basis to exclude false-positive results. PMID- 26678730 TI - The use of animal models in homeopathic research--a review of 2010-2014 PubMed indexed papers. AB - BACKGROUND: In the 1990s, a study was performed on the effects of highly diluted thyroxine on frog metamorphosis. This model represented one of the most discussed examples of the biological effects of high dilutions over the next two decades. In 2010, another critical conceptual review of the use of animal models in homeopathy and high-dilution research was published. The main contribution of these studies was the elucidation of the biological features and phenomenology of the effects of high dilutions on living systems, representing an important step forward in our understanding of the mechanisms of action of homeopathic medicines. METHODS: We performed a further review of this line of investigation using the same methods. Fifty-three articles that were indexed in the PubMed database and used 12 different animal species were systematically evaluated. Only a fraction of the studies (29/53) reported herein were performed with "ultra high" dilutions. The other studies were performed with dilutions in ranges below 10(-23) (14/53 articles) or commercial complexes (10/53 articles). RESULTS: Only two articles reported negative results; both used in vivo protocols to test commercial complexes, one in fish and one in bees. The quality of the employed techniques improved in 2010-2014 compared with the studies that were reviewed previously in 2010, with the inclusion of more ethically refined protocols, including in vitro primary cell cultures and ex vivo studies (10/53 articles), often with three or more replicates and analyses of epigenetic mechanisms that were previously unknown in 2010. CONCLUSION: In our updated review of the past 5 years, we found further demonstrations of the biological effects of homeopathy using more refined animal models and in vitro techniques. PMID- 26678731 TI - Physiological effects of homeopathic medicines in closed phials--a critical evaluation. AB - BACKGROUND: Phials containing high dilutions of homeopathic remedies are commonly utilized in diagnostic tools in combination with electro acupuncture measuring electrical conductivity of the skin. The present research aimed to elucidate the interaction of the homeopathic remedy and the human organism. METHOD: The study protocol included the transition of a healthy subject to a diseased state utilizing a sub-harmful dose of a toxin. Subsequently, the subject was exposed to a homeopathic or placebo remedy in a closed glass phial and electrical conductivity was measured in open as well as in blind trials. A total of 229 data were collected from open trials and 750 data from blind trials. RESULT: The experimental data showed that homoeopathic remedies in closed glass phials may influence the electrical skin conductivity. The results of the blind trials differed considerably from those of the open trials. The percentage of correctly identified (verum and placebo) phials in the open trials (85%) was statistically different from those in the blind trials (65%). In both types of trials, however, the difference between the sealed phials containing the homeopathic medicine and the placebo was statistically significant. The results of measurements are directly linked to the way in which the tester holds the electrode in one hand and the subject's finger in the other, while putting pressure on the electrode. CONCLUSION: It was concluded that the tester's muscle tone is the intermediary in unconsciously selecting which phial influenced him in his specific contact with the subject. PMID- 26678732 TI - From high dilutions to digital biology: the physical nature of the biological signal. AB - The memory of water was a radical idea that arose in the laboratory of Jacques Benveniste in the late 1980s. Twenty-five years have passed and yet the often angry debate on its merits continues despite the increasing number of scientists who have reported confirmation of the basic results. One working hypothesis was that molecules can communicate with each other, exchanging information without being in physical contact and that at least some biological functions can be mimicked by certain energetic modes characteristics of a given molecule. These considerations informed exploratory research which led to the speculation that biological signaling might be transmissible by electromagnetic means. Around 1991, the transfer of specific molecular signals to sensitive biological systems was achieved using an amplifier and electromagnetic coils. In 1995, a more sophisticated procedure was established to record, digitize and replay these signals using a multimedia computer. From a physical and chemical perspective, these experiments pose a riddle, since it is not clear what mechanism can sustain such 'water memory' of the exposure to molecular signals. From a biological perspective, the puzzle is what nature of imprinted effect (water structure) can impact biological function. A parallel can be drawn between this debate on the memory of water, which presumes that the action of molecules is mediated by an electromagnetic phenomenon, and the often acrimonious debate on the transmission of nerve influxes via synaptic transfer of specific molecules, neurotransmitters. The latter debate began in 1921 with the first experiments by Loewi and was still active in 1949, 28 years later. A strong reluctance to accept research that questions basic aspects of long-accepted biochemical paradigms is to be expected. In this paper we will provide a brief summary of experiments relating to the memory of water: the earlier work on high dilutions (HD) and then the experiments, which followed and continue today, on digital biology. PMID- 26678733 TI - Electromagnetic and magnetic vector potential bio-information and water. AB - This work developed over the past 40 years starting from dielectric measurements on enzymes and the subsequent finding that the measurements were affected by electric, magnetic, electromagnetic fields and quantum fields. A request for help in the diagnosis and therapy of chemically sensitive patients who had become sensitive to their electromagnetic environment came in 1982. The same symptoms could be provoked by a chemical or a frequency challenge and this led to an appreciation of the synergy between chemical and frequency environmental sensitivities. Experimental cooperation with theoretical physicist Herbert Frohlich FRS and others led to an understanding of the physics of coherent water in living systems and a mechanism for the memory of water for coherent frequencies. In a coherent system there are interacting frequencies proportionate to any velocity the system will support, in particular the velocity of light and the velocity of coherence diffusion. Thus, there can be biological interaction between the optical, microwave and ELF spectral regions. Frequency modulation of light scattered by bio-fields and its retention in recorded images is discussed. A 'nil-potent' frequency can erase a frequency signature and thence affect a biological system. Homeopathy is interpreted through the biological effects of coherent frequencies derived from the frequency signature of the 'Mother Tincture' and developed through dilution and succussion. A homeopathic potency has a frequency signature therefore it must be able to have a biological effect. PMID- 26678734 TI - Experimental physical methods and theories--then and now. AB - INTRODUCTION: A first evaluation of fundamental research into the physics and physiology of Ultra high dilutions (UHDs) was conducted by the author in 1994(1). In this paper we revisit methods and theories from back then and follow their paths through their evolution and contribution to new knowledge in UHD research since then. METHOD: Physical methods and theories discusses in our anthology on UHD in 1994(1) form the basis for tracing ideas and findings along their path of further development and impact on new knowledge in UHD. RESULTS: Experimental approaches to probe physical changes in homeopathic preparations have become more sophisticated over past two decades, so did the desire to report results to a scientific standard that is on par with those in specialist literature. The same cannot be said about underlying supporting theoretical models and simulations. CONCLUSION: Grant challenges in science often take a more targeted and more concerted approach to formulate a research question and then look for answers. A concerted effort to focus on one hypothesized physical aspect of a well-defined homeopathic preparation may help aligning experimental methods with theoretical models and, in doing so, help to gain a deeper understanding of the whole body of insights and data produced. PMID- 26678735 TI - Publications on experimental physical methods to investigate ultra high dilutions -an assessment on quality. AB - INTRODUCTION: Our first evaluation of fundamental research into the physics and physiology of Ultra High Dilution (UHD) was conducted in 1994. Since then, in 2003, Becker-Witt et al. conducted a more systematic evaluation of the literature and established the Score for Assessment of Physical Experiments on Homeopathy (SAPEH). While this evaluation focused on experimental methodologies, Stock Schroer et al., in 2009, formulated a detailed guideline for authors on Reporting Experiments in Homeopathic Basic research (REHBaR) to promote a high standard in research as well as in its communication in scientific literature. METHOD: In this paper, we evaluate publications on basic research into the physics of UHD since the decade following the presentation of the SAPEH score (2004-2014), and present the state of progress in this field. RESULTS: Fundamental research into the physics of UHD has been reported at a steady rate over the past 60 years. Reported research of high quality as per SAPEH scoring appears to be still the exception rather than standard. CONCLUSION: Considering the importance of a fundamental understanding of what makes a UHD preparation, results of this study suggest that it may be beneficial to this field of fundamental research if grant challenges are approached in strategic way similar to other grant challenges in science. PMID- 26678736 TI - Observations on entanglement, non-locality and ultra-high dilutions. AB - INTRODUCTION: Fundamental research into the scientific basis of the manufacture of ultra-high dilutions and their working in applications has evolved over the past twenty years since our last critical analysis of the field was published in 1994. New contenders from the realm of physics (entanglement, non-locality) have entered the scene. The vast majority within the community of the application of ultra-high dilutions are not physicists. This paper attempts to elucidate the concepts of entanglement, non-locality and their application in ultra-high dilution research (UHD). METHOD: A selected study on the activity of fundamental research into UHD is performed to gain insight into trends of development activity of fundamental research in this area. In an attempt to nurture further development of theoretical models in fundamental research in UHD, an attempt is made to made recent theoretical concepts more accessible to the larger community including practitioners, policy makers and beneficiaries of UHD. RESULTS: Fundamental research in UHD had a period of prolific activity and recognition at the turn of the millennium until about ten years ago. Since then, research output as well as its recognition receded sharply suggesting that a period of reflection and consolidation may be in progress. CONCLUSION: The study and the knowledge gained from more recent theoretical models in UHD and entanglement suggest that there may be some benefit in stocktaking of what we really know about the fundamental workings of UHD as well as identifying or developing models that include measurable predictors that go beyond metaphorical descriptors. PMID- 26678737 TI - Scientific proving of ultra high dilutions on humans. AB - BACKGROUND: Homeopathic drug provings or pathogenetic trials (HPTs) are the pillar of homeopathy. This review summarizes the authors' findings and interpretations derived from a series of homeopathic drug proving between 1994 and 2015. It gives an overview over a series of attempts to use modern scientific experimental methodology to answer the question, whether such HPTs produce symptoms in healthy volunteers that can be distinguished from placebo symptoms. METHODS: Various experimental models were used: repeated crossover trials with categorical data collection, and a single-case, randomised study. Final models use diligent qualitative data-collection in experienced volunteers. In those, raters decide whether symptoms are typical for a remedy delivered or not. The design is triple-blind and placebo-controlled. RESULT: While previous attempts were inconclusive, this new model allowed to separate placebo symptoms from verum symptoms repeatedly in a series of two definitive studies following promising pilot studies. Results were statistically significant. Also, some signs of the purported non-local signature of homeopathic effects were visible, and the consequences for future methodology is discussed. CONCLUSION: Provided some cautionary notes are taken into account, HPTs can be used to separate out true specific symptoms from placebo symptoms. By the same token this is a road to experimental proof that homeopathic remedies are not just placebos. However, this needs to be taken forward by independent groups. PMID- 26678738 TI - Controlled clinical studies of homeopathy. AB - INTRODUCTION: Observations about controlled clinical trials expressed by Max Haidvogl in the book Ultra High Dilution (1994) have been appraised from a perspective two decades later. The present commentary briefly examines changes in homeopathy research evidence since 1994 as regards: the published number of randomised controlled trials (RCTs), the use of individualised homeopathic intervention, the 'proven efficacy of homeopathy', and the quality of the evidence. METHODS: The commentary reflects the details of RCTs that are available in a recently published literature review and by scrutiny of systematic reviews of RCTs in homeopathy. RESULTS: The homeopathy RCT literature grew by 309 records in the 18 years that immediately followed Haidvogl's article, with more than a doubling of the proportion that investigated individualised homeopathy. Discounting one prior publication, the entire systematic review literature on homeopathy RCTs post-dates 1994. A total of 36 condition-specific systematic reviews have been identified in the peer-reviewed literature: 16 of them reported positive, or tentatively positive, conclusions about homeopathy's clinical effectiveness; the other 20 were negative or non-conclusive. Reviews typically have been restricted in the strength of their conclusions by the low quality of the original RCT evidence. Three comprehensive systematic reviews concluded, cautiously, that homeopathy may differ from placebo; a fourth such review reached negative conclusions. A recent high-quality meta-analysis concluded that medicines prescribed in individualised homeopathic treatment may have small, specific, effects. CONCLUSIONS: Despite important growth in research activity since 1994, concerns about study quality limit the interpretation of available RCT data. The question whether homeopathic intervention differs from placebo awaits decisive answer. PMID- 26678739 TI - Reporting Experiments in Homeopathic Basic Research (REHBaR). AB - INTRODUCTION: The aim of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of Reporting Experiments in Homeopathic Basic Research (REHBaR). Main focus was in the field of biochemical and biological experiments. So far, there was no guideline for scientists and authors available, unlike criteria catalogues common in clinical research. METHODS: A Delphi Process was conducted among experts who published experimental work within the last five years in this field. The process included a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. RESULTS: A checklist of 23 items was achieved, augmented with detailed examples how to handle each item while compiling a publication. Background, objectives and possible hypotheses are necessary to be given in the part 'introduction'. The section 'materials and methods' is the most important part, where a detailed description of chosen controls, object of investigation, experimental setup, replication, parameters, intervention, allocation, blinding, and statistical methods is mandatory. In the 'results' section sufficient details on analysed data, descriptive as well as inferential are needed. Moreover, authors should discuss their results and interpret them in the context of current evidence. REHBaR was compiled for authors when preparing their manuscripts, and to be used by scientific journals in the reviewing process. CONCLUSIONS: Reporting experiments in basic research in homeopathy is an important issue to state the quality and validity of gained results. A guideline for REHBaR seemed to be the first step to come to a commitment what information is necessary to be given in a paper. More than that, the catalogue can serve as a statement what the standards in good basic research should be. PMID- 26678740 TI - Update on preliminary elements of a theory of ultra high dilutions. AB - INTRODUCTION: The different mechanisms: A. of the interaction between the molecular mother substance and the solvent water or ethanol B. of the storage of molecule-specific information in the solvent. C. the physiological basis of the sensitivity of the living organism towards an ultra high dilution (UHD). D. the mechanism of the interaction of the test dilution with the organism are largely unknown. Several ideas have been postulated, and experiments to test them carried out in physics and in biology. METHOD: The authors revisited a 1994 contribution on 'preliminary elements of a theory on UHDs' and updated it with regard to more recent literature and research findings. RESULTS: Although the experimental basis can still be questioned in most cases, remarkable fundamental observations have been made to explain the effects of UHDs. For some topics in question, it appears that information specific properties of the diluted substance to be transferred is stored by means electromagnetic fields. The interaction between the UHD and the organism seems to be electromagnetic in nature. The transmission of information from (bio-)molecules to the UHD is of special interest. Again, electromagnetic actions and vector potential fields appear to be implicated. CONCLUSION: The mechanisms of information storage and transfer in UHDs are far from fully understood, but progress has been made at experimental and theoretical levels. PMID- 26678741 TI - Aims of homeopathy research, 1994 and 2015. PMID- 26678742 TI - Practical guidance for prescribing trazodone extended-release in major depression. AB - INTRODUCTION: Treatment of major depressive disorder aims for symptom remission and recovery of function, and involves a multifaceted approach including drug therapy, evidence-based psychotherapy, and electroconvulsive therapy, according to disease severity. Antidepressant monotherapy is generally the first-line approach for moderate to severe major depressive disorder (with or without psychotherapy). In some severe cases, patients may require the addition of antipsychotic therapy, electroconvulsive therapy, or antidepressant combination therapy. AREAS COVERED: This article examines the use of trazodone in major depressive disorder, with a focus on practical guidance regarding the use of trazodone extended-release (Contramid((r))). EXPERT OPINION: The extended-release once-a-day formulation of trazodone may provide a combination of efficacy and improved tolerability over other antidepressants and over the conventional immediate-release formulation. PMID- 26678743 TI - Disparities in female urologic case distribution with new subspecialty certification and surgeon gender. AB - AIMS: To examine surgical case volume characteristics in certifying urologists associated with common female urologic procedures to evaluate the practice patterns, given the recent establishment of subspecialty certification in Female Pelvic Medicine and Reconstructive Surgery (FPMRS) and changes in urologist gender composition. METHODS: Six-month case log data of certifying urologists (2003-2013) was obtained from the American Board of Urology (ABU). We examined case logs for 26 CPT codes for common female urologic procedures focused on four procedure groups: incontinence, prolapse, vesicovaginal fistula (VVF), and revision/removal of vaginal mesh/graft. RESULTS: Among 4802 urologists logging at least one female urology case, 43,949 (55.6% of all cases) incontinence, 30,983 (39.2%) prolapse, 451 (0.6%) VVF, and 3643 (4.6%) revision of mesh/graft surgeries were identified. While 90.8% logging at least one female CPT code were men, women surgeons (9.2%) accounted for a disproportionate volume (22.6%) of cases. With initiation of the FPMRS subspecialty certification in 2011, 225 FPMRS candidates (out of 1716 certifying urologists) were identified, compared to 367 (out of 3828 certifying urologists) female subspecialists prior to 2011. FPMRS accounted for 56.7% of prolapse, 62.9% VVF, 59.0% mesh/graft revisions, and 41.9% of incontinence surgeries, compared to female specialists before 2011 (39.1%, 42.4%, 41.5%, and 21.6% respectively (all P < 0.001)). CONCLUSIONS: A growing proportion of female urologic cases are performed by female subspecialists, with a significant increase since initiation of FPMRS subspecialty certification. Women surgeons account for a disproportionate volume of these cases despite remaining a minority of certifying urologists and female subspecialists. Neurourol. Urodynam. 36:399-403, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26678744 TI - Correction: Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease. PMID- 26678747 TI - Functional redundancy of transcription factors explains why most binding targets of a transcription factor are not affected when the transcription factor is knocked out. AB - BACKGROUND: Biologists are puzzled by the extremely low percentage (3%) of the binding targets of a yeast transcription factor (TF) affected when the TF is knocked out, a phenomenon observed by comparing the TF binding dataset and TF knockout effect dataset. RESULTS: This study gives a plausible biological explanation of this counterintuitive phenomenon. Our analyses find that TFs with high functional redundancy show significantly lower percentage than do TFs with low functional redundancy. This suggests that functional redundancy may lead to one TF compensating for another, thus masking the TF knockout effect on the binding targets of the knocked-out TF. In addition, we show that seven classes of genes (lowly expressed genes, TATA box-less genes, genes containing a nucleosome free region immediately upstream of the transcriptional start site (TSS), genes with low transcriptional plasticity, genes with a low number of bound TFs, genes with a low number of TFBSs, and genes with a short average distance of TFBSs to the TSS) are insensitive to the knockout of their promoter-binding TFs, providing clues for finding other biological explanations of the surprisingly low percentage of the binding targets of a TF affected when the TF is knocked out. CONCLUSIONS: This study shows that one property of TFs (functional redundancy) and seven properties of genes (expression level, TATA box, nucleosome, transcriptional plasticity, the number of bound TFs, the number of TFBSs, and the average distance of TFBSs to the TSS) may be useful for explaining a counterintuitive phenomenon: most binding targets of a yeast transcription factor are not affected when the transcription factor is knocked out. PMID- 26678746 TI - Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide Independent Nitroxide Label. AB - Guanine-rich oligonucleotides can form a unique G-quadruplex (GQ) structure with stacking units of four guanine bases organized in a plane through Hoogsteen bonding. GQ structures have been detected in vivo and shown to exert their roles in maintaining genome integrity and regulating gene expression. Understanding GQ conformation is important for understanding its inherent biological role and for devising strategies to control and manipulate functions based on targeting GQ. Although a number of biophysical methods have been used to investigate structure and dynamics of GQs, our understanding is far from complete. As such, this work explores the use of the site-directed spin labeling technique, complemented by molecular dynamics simulations, for investigating GQ conformations. A nucleotide independent nitroxide label (R5), which has been previously applied for probing conformations of noncoding RNA and DNA duplexes, is attached to multiple sites in a 22-nucleotide DNA strand derived from the human telomeric sequence (hTel-22) that is known to form GQ. The R5 labels are shown to minimally impact GQ folding, and inter-R5 distances measured using double electron-electron resonance spectroscopy are shown to adequately distinguish the different topological conformations of hTel-22 and report variations in their occupancies in response to changes of the environment variables such as salt, crowding agent, and small molecule ligand. The work demonstrates that the R5 label is able to probe GQ conformation and establishes the base for using R5 to study more complex sequences, such as those that may potentially form multimeric GQs in long telomeric repeats. PMID- 26678745 TI - Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice. AB - Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case-control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date-matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41-0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-alpha, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-gamma by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects. PMID- 26678748 TI - Biofilm formation in Candida glabrata: What have we learnt from functional genomics approaches? AB - Biofilms are a source of therapeutic failures because of their intrinsic tolerance to antimicrobials. Candida glabrata is one of the pathogenic yeasts that is responsible for life-threatening disseminated infections and able to form biofilms on medical devices such as vascular and urinary catheters. Recent progresses in the functional genomics of C. glabrata have been applied to the study of biofilm formation, revealing the contribution of an array of genes to this process. In particular, the Yak1 kinase and the Swi/Snf chromatin remodeling complex have been shown to relieve the repression exerted by subtelomeric silencing on the expression of the EPA6 and EPA7 genes, thus allowing the encoded adhesins to exert their key roles in biofilm formation. This provides a framework to evaluate the contribution of other genes that have been genetically linked to biofilm development and, based on the function of their orthologs in Saccharomyces cerevisiae, appear to have roles in adaptation to nutrient deprivation, calcium signaling, cell wall remodeling and adherence. Future studies combining the use of in vitro and animal models of biofilm formation, omics approaches and forward or reverse genetics are needed to expand the current knowledge of C. glabrata biofilm formation and reveal the mechanisms underlying their antifungal tolerance. PMID- 26678749 TI - Yeast MRX deletions have short chronological life span and more triacylglycerols. AB - Saccharomyces cerevisiae is an excellent model organism for lipid research. Here, we have used yeast haploid RAdiation Damage (RAD) deletion strains to study life span and lipid storage patterns. RAD genes are mainly involved in DNA repair mechanism and hence, their deletions have resulted in shorter life span. Viable RAD mutants were screened for non-polar lipid content, and some of the mutants showed significantly high amounts of triacylglycerol (TAG) and steryl ester, besides short chronological life span. Among these, RAD50, MRE11 and XRS2 form a complex, MRX that is involved in homologous recombination that showed an increase in the amount of TAG. Microarray data of single MRX deletions revealed that besides DNA damage signature genes, lipid metabolism genes are also differentially expressed. Lipid biosynthetic genes (LPP1, SLC1) were upregulated and lipid hydrolytic gene (TGL3) was downregulated. We observed that rad50Delta, mre11Delta, xrs2Delta and mrxDelta strains have high number of lipid droplets (LDs) with fragmented mitochondria. These mutants have a short chronological life span compared to wild type. Aged wild-type cells also accumulated TAG with LDs of ~2.0 MUm in diameter. These results suggest that TAG accumulation and big size LDs could be possible markers for premature or normal aging. PMID- 26678750 TI - A Text-Messaging and Pedometer Program to Promote Physical Activity in People at High Risk of Type 2 Diabetes: The Development of the PROPELS Follow-On Support Program. AB - BACKGROUND: Mobile technologies for health (mHealth) represent a promising strategy for reducing type 2 diabetes (T2DM) risk. The PROPELS trial investigates whether structured group-based education alone or supplemented with a follow-on support program combining self-monitoring with pedometers and tailored text messaging is effective in promoting and maintaining physical activity among people at high risk of T2DM. OBJECTIVE: This paper describes the iterative development of the PROPELS follow-on support program and presents evidence on its acceptability and feasibility. METHODS: We used a modified mHealth development framework with four phases: (1) conceptualization of the follow-on support program using theory and evidence, (2) formative research including focus groups (n=15, ages 39-79 years), (3) pre-testing focus groups using a think aloud protocol (n=20, ages 52-78 years), and (4) piloting (n=11). Analysis was informed by the constant comparative approach, with findings from each phase informing subsequent phases. RESULTS: The first three phases informed the structure, nature, and content of the follow-on support program, including the frequency of text messages, the need for tailored content and two-way interaction, the importance of motivational messages based on encouragement and reinforcement of affective benefits (eg, enjoyment) with minimal messages about weight and T2DM risk, and the need for appropriate language. The refined program is personalized and tailored to the individual's perceived confidence, previous activity levels, and physical activity goals. The pilot phase indicated that the program appeared to fit well with everyday routines and was easy to use by older adults. CONCLUSIONS: We developed a feasible and innovative text messaging and pedometer program based on evidence and behavior change theory and grounded in the experiences, views, and needs of people at high diabetes risk. A large scale trial is testing the effectiveness of this 4-year program over and above structured group education alone. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 83465245; http://www.controlled trials.com/ISRCTN83465245/83465245 (Archived by WebCite at http://www.webcitation.org/6dfSmrVAe). PMID- 26678751 TI - A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules. AB - Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S) and the small (40S/30S) subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations. PMID- 26678752 TI - Thrombectomy using a stent retriever with artificially induced vertebral artery vasospasm in a patient with acute basilar artery occlusion: a case report. AB - An acute basilar artery occlusion is not an uncommon cause of stroke. It represents 6-10% of large vessel strokes and has been associated with poor clinical outcomes. Multimodal treatments have been introduced to recanalise a basilar artery occlusion successfully. However, all mechanical thrombectomy devices are not always usable in an emergent situation. We present a case of basilar artery occlusion treated with a stent retriever assisted by a vertebral artery vasospasm. We attempted thrombectomy with a stent retriever several times. However, the captured thrombus was not pulled out and migrated to the distal basilar artery and posterior cerebral artery due to anterograde flow of the vertebral artery. We carefully advanced the catheter into the distal vertebral artery and generated a vasospasm. The vertebral artery vasospasm reduced the forward flow significantly like a balloon-guided catheter. The thrombus was pulled out with the stent. PMID- 26678753 TI - Microstructural abnormalities of the trigeminal nerve by diffusion-tensor imaging in trigeminal neuralgia without neurovascular compression. AB - Microstructural changes of the trigeminal nerve in trigeminal neuralgia due to neurovascular compression have been reported by using diffusion tensor imaging. Other aetiologies such as primary demyelinating lesions, brain stem infarction and nerve root infiltration by tumour affecting the trigeminal pathway may also present as trigeminal neuralgia. The aim of this study was to evaluate the microstructural tissue abnormalities in the trigeminal nerve in symptomatic trigeminal neuralgia not related to neurovascular compression using diffusion tensor imaging. Mean values of the quantitative diffusion parameters of trigeminal nerve, fractional anisotropy and apparent diffusion coefficient, were measured in a group of four symptomatic trigeminal neuralgia patients without neurovascular compression who showed focal non-enhancing T2-hyperintense lesions in the pontine trigeminal pathway. These diffusion parameters were compared between the affected and unaffected sides in the same patient and with four age matched healthy controls. Cranial magnetic resonance imaging revealed hyperintense lesions in the dorsolateral part of the pons along the central trigeminal pathway on T2-fluid-attenuated inversion recovery sequences. The mean fractional anisotropy value on the affected side was significantly decreased (P = 0.001) compared to the unaffected side and healthy controls. Similarly, the mean apparent diffusion coefficient value was significantly higher (P = 0.001) on the affected side compared to the unaffected side and healthy controls. The cause of trigeminal neuralgia in our patients was abnormal pontine lesions affecting the central trigeminal pathway. The diffusion tensor imaging results suggest that microstructural tissue abnormalities of the trigeminal nerve also exist even in non-neurovascular compression-related trigeminal neuralgia. PMID- 26678754 TI - Zirconia based superhydrophobic coatings on cotton fabrics exhibiting excellent durability for versatile use. AB - A fluorinated silyl functionalized zirconia was synthesized by the sol-gel method to fabricate an extremely durable superhydrophobic coating on cotton fabrics by simple immersion technique. The fabric surfaces firmly attached with the coating material through covalent bonding, possessed superhydrophobicity with high water contact angle ~163 +/- 1 degrees , low hysteresis ~3.5 degrees and superoleophilicity. The coated fabrics were effective to separate oil/water mixture with a considerably high separation efficiency of 98.8 wt% through ordinary filtering. Presence of highly stable (chemically and mechanically) superhydrophobic zirconia bonded with cellulose makes such excellent water repelling ability of the fabrics durable under harsh environment conditions like high temperature, strong acidic or alkaline solutions, different organic solvents and mechanical forces including extensive washings. Moreover, these coated fabrics retained self-cleanable superhydrophobic property as well as high water separation efficiency even after several cycles, launderings and abrasions. Therefore, such robust superhydrophobic ZrO2 coated fabrics have strong potential for various industrial productions and uses. PMID- 26678757 TI - Dear Dr. Olry. PMID- 26678755 TI - The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status. AB - BACKGROUND: Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects. METHODS: Abdominal subcutaneous adipose tissue (SAT) samples were obtained from morbidly obese women (n = 18) before and 13.3 +/- 0.37 months after BS. Obese women were stratified into two groups: normoglycemic (NG; Glu < 100 mg/dl, HbA1c <5.7 %) or insulin resistant (IR; Glu 100-126 mg/dl, HbA1c 5.7-6.4 %) (n = 9/group). A multi-comparative proteomic analysis was employed to identify differentially regulated SAT proteins by BS and/or the degree of insulin sensitivity. Serum levels of metabolic, inflammatory, and anti-oxidant markers were also analyzed. RESULTS: Before surgery, NG and IR subjects exhibited differences in AT proteins related to inflammation, metabolic processes, the cytoskeleton, and mitochondria. BS caused comparable weight reductions and improved glucose homeostasis in both groups. However, BS caused dissimilar changes in metabolic enzymes, inflammatory markers, cytoskeletal components, mitochondrial proteins, and angiogenesis regulators in NG and IR women. CONCLUSIONS: BS evokes significant molecular rearrangements indicative of improved AT function in morbidly obese women at either low or high metabolic risk, though selective adaptive changes in key cellular processes occur depending on the initial individual's metabolic status. PMID- 26678756 TI - Evidence from pyrosequencing indicates that natural variation in animal personality is associated with DRD4 DNA methylation. AB - Personality traits are heritable and respond to natural selection, but are at the same time influenced by the ontogenetic environment. Epigenetic effects, such as DNA methylation, have been proposed as a key mechanism to control personality variation. However, to date little is known about the contribution of epigenetic effects to natural variation in behaviour. Here, we show that great tit (Parus major) lines artificially selected for divergent exploratory behaviour for four generations differ in their DNA methylation levels at the dopamine receptor D4 (DRD4) gene. This D4 receptor is statistically associated with personality traits in both humans and nonhuman animals, including the great tit. Previous work in this songbird failed to detect functional genetic polymorphisms within DRD4 that could account for the gene-trait association. However, our observation supports the idea that DRD4 is functionally involved in exploratory behaviour but that its effects are mediated by DNA methylation. While the exact mechanism underlying the transgenerational consistency of DRD4 methylation remains to be elucidated, this study shows that epigenetic mechanisms are involved in shaping natural variation in personality traits. We outline how this first finding provides a basis for investigating the epigenetic contribution to personality traits in natural systems and its subsequent role for understanding the ecology and evolution of behavioural consistency. PMID- 26678758 TI - Fluorescence Quenching Property of C-Phycocyanin from Spirulina platensis and its Binding Efficacy with Viable Cell Components. AB - Phycocyanin is a natural brilliant blue colored, fluorescent protein, which is commonly present in cyanobacteria. In this study, C-phycocyanin was extracted and purified from Spirulina platensis, which are multicellular and filamentous cyanobacteria of greater importance because of its various biological and pharmacological potential. It was analyzed for its binding affinity towards blood cells, algal cells, genomic DNA of microalgae, and bacteria at different temperature and incubation time. It showed good binding affinity with these components even at low concentration of 2.5 MUM. The purpose of this study was to evaluate the applicability of C-phycocyanin as a green fluorescent dye substituting carcinogenic chemical dyes. PMID- 26678759 TI - Local Anesthetic Systemic Toxicity (LAST): Not Gone, Hopefully Not Forgotten. PMID- 26678760 TI - Creating, and Protecting, the American Society of Regional Anesthesia and Pain Medicine's Intellectual Property. PMID- 26678761 TI - Block Performance and Risk Factors for Nerve Injury. PMID- 26678762 TI - Revising the 2012 American Society of Regional Anesthesia and Pain Medicine Checklist for Local Anesthetic Systemic Toxicity: A Call to Resolve Ambiguity in Clinical Implementation. PMID- 26678763 TI - The SPANK Block: A Selective Sensory, Single-Injection Solution for Posterior Pain After Total Knee Arthroplasty. PMID- 26678782 TI - Gordonia didemni sp. nov. an actinomycete isolated from the marine ascidium Didemnum sp. AB - A novel actinobacterium, designated isolate B204(T), was isolated from a marine ascidian Didemnum sp., collected from Sao Paulo, Brazil, and its taxonomic position established using data from a polyphasic study. The organism showed a combination of chemotaxonomic and morphological characteristics consistent with its classification in the genus Gordonia and formed a distinct phyletic line in the Gordonia 16S rRNA gene tree. It was closely related to Gordonia terrae DSM 43249(T) (99.9 % 16S rRNA gene sequence similarity) and Gordonia lacunae DSM 45085(T) (99.3 % 16S rRNA gene sequence similarity) but was distinguished from these strains by a moderate level of DNA-DNA relatedness (63.0 and 54.7 %) and discriminatory phenotypic properties. Based on the data obtained, the isolate B204(T) (=CBMAI 1069(T) = DSM 46679(T)) should therefore be classified as the type strain of a novel species of the genus Gordonia, for which the name Gordonia didemni sp. nov. is proposed. PMID- 26678783 TI - Thermoactinomyces khenchelensis sp. nov., a filamentous bacterium isolated from soil sediment of a terrestrial hot spring. AB - A novel thermophilic filamentous bacterium, designated strain T36(T), was isolated from soil sediment sample from a hot spring source collected in Khenchela province, Algeria. Strain T36(T) was identified as a member of the genus Thermoactinomyces by a polyphasic approach. Strain T36(T) was observed to form white aerial mycelium and non-coloured to pale yellow substrate mycelium, both producing endospores, sessile or borne by short sporophores. The optimum growth temperature and pH were found to be 37-55 degrees C and 7.0-9.0, respectively and the optimum NaCl concentration for growth was found to be 0-7 % (w/v). The diagnostic diamino acid in the cell wall peptidoglycan was identified as meso-diaminopimelic acid. The predominant menaquinone of strain T36(T) was identified as MK-7 (H0). The major fatty acids were found to be iso-C15:0 and iso C17:0. The phospholipids detected were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphoglycolipid. The chemotaxonomic properties of strain T36(T) are consistent with those shared by members of the genus Thermoactinomyces. 16S rRNA gene sequence analysis indicated that the sequence similarities between strain T36(T) and Thermoactinomyces species with validly published names were less than 98 %. Based on the combined genotypic and phenotypic evidence, it is proposed that strain T36(T) should be classified as representative of a novel species, for which the name Thermoactinomyces khenchelensis sp. nov. is proposed. The type strain is T36(T) (=DSM 45951(T) = CECT 8579(T)). PMID- 26678784 TI - Secretome analysis of chickpea reveals dynamic extracellular remodeling and identifies a Bet v1-like protein, CaRRP1 that participates in stress response. AB - Secreted proteins maintain cell structure and biogenesis besides acting in signaling events crucial for cellular homeostasis during stress adaptation. To understand the underlying mechanism of stress-responsive secretion, the dehydration-responsive secretome was developed from suspension-cultured cells of chickpea. Cell viability of the suspension culture remained unaltered until 96 h, which gradually declined at later stages of dehydration. Proteomic analysis led to the identification of 215 differentially regulated proteins, involved in a variety of cellular functions that include metabolism, cell defence, and signal transduction suggesting their concerted role in stress adaptation. One-third of the secreted proteins were devoid of N-terminal secretion signals suggesting a non-classical secretory route. Screening of the secretome identified a leaderless Bet v 1-like protein, designated CaRRP1, the export of which was inhibited by brefeldin A. We investigated the gene structure and genomic organization and demonstrated that CaRRP1 may be involved in stress response. Its expression was positively associated with abiotic and biotic stresses. CaRRP1 could complement the aberrant growth phenotype of yeast mutant, deficient in vesicular transport, indicating a partial overlap of protein secretion and stress response. Our study provides the most comprehensive analysis of dehydration-responsive secretome and the complex metabolic network operating in plant extracellular space. PMID- 26678786 TI - The capacity to maintain ion and water homeostasis underlies interspecific variation in Drosophila cold tolerance. AB - Many insects, including Drosophila, succumb to the physiological effects of chilling at temperatures well above those causing freezing. Low temperature causes a loss of extracellular ion and water homeostasis in such insects, and chill injuries accumulate. Using an integrative and comparative approach, we examined the role of ion and water balance in insect chilling susceptibility/ tolerance. The Malpighian tubules (MT), of chill susceptible Drosophila species lost [Na(+)] and [K(+)] selectivity at low temperatures, which contributed to a loss of Na(+) and water balance and a deleterious increase in extracellular [K(+)]. By contrast, the tubules of chill tolerant Drosophila species maintained their MT ion selectivity, maintained stable extracellular ion concentrations, and thereby avoided injury. The most tolerant species were able to modulate ion balance while in a cold-induced coma and this ongoing physiological acclimation process allowed some individuals of the tolerant species to recover from chill coma during low temperature exposure. Accordingly, differences in the ability to maintain homeostatic control of water and ion balance at low temperature may explain large parts of the wide intra- and interspecific variation in insect chilling tolerance. PMID- 26678787 TI - Propagation of Love waves with surface effects in an electrically-shorted piezoelectric nanofilm on a half-space elastic substrate. AB - The propagation of Love waves in the structure consisting of a nanosized piezoelectric film and a semi-infinite elastic substrate is investigated in the present paper with the consideration of surface effects. In our analysis, surface effects are taken into account in terms of the surface elasticity theory and the electrically-shorted conditions are adopted on the free surface of the piezoelectric film and the interface between the film and the substrate. This work focuses on the new features in the dispersion relations of different modes due to surface effects. It is found that with the existence of surface effects, the frequency dispersion of Love waves shows the distinct dependence on the thickness and the surface constants when the film thickness reduces to nanometers. In general, phase velocities of all dispersion modes increase with the decrease of the film thickness and the increase of the surface constants. However, surface effects play different functions in the frequency dispersions of different modes, especially for the first mode dispersion. Moreover, different forms of Love waves are observed in the first mode dispersion, depending on the presence of the surface effects on the surface and the interface. PMID- 26678788 TI - Low complex subspace minimum variance beamformer for medical ultrasound imaging. AB - Minimum variance (MV) beamformer enhances the resolution and contrast in the medical ultrasound imaging at the expense of higher computational complexity with respect to the non-adaptive delay-and-sum beamformer. The major complexity arises from the estimation of the L*L array covariance matrix using spatial averaging, which is required to more accurate estimation of the covariance matrix of correlated signals, and inversion of it, which is required for calculating the MV weight vector which are as high as O(L(2)) and O(L(3)), respectively. Reducing the number of array elements decreases the computational complexity but degrades the imaging resolution. In this paper, we propose a subspace MV beamformer which preserves the advantages of the MV beamformer with lower complexity. The subspace MV neglects some rows of the array covariance matrix instead of reducing the array size. If we keep eta rows of the array covariance matrix which leads to a thin non-square matrix, the weight vector of the subspace beamformer can be achieved in the same way as the MV obtains its weight vector with lower complexity as high as O(eta(2)L). More calculations would be saved because an eta*L covariance matrix must be estimated instead of a L*L. We simulated a wire targets phantom and a cyst phantom to evaluate the performance of the proposed beamformer. The results indicate that we can keep about 16 from 43 rows of the array covariance matrix which reduces the order of complexity to 14% while the image resolution is still comparable to that of the standard MV beamformer. We also applied the proposed method to an experimental RF data and showed that the subspace MV beamformer performs like the standard MV with lower computational complexity. PMID- 26678789 TI - Ultrasound measurements of segmental temperature distribution in solids: Method and its high-temperature validation. AB - A novel approach that uses noninvasive ultrasound to measure the temperature distribution in solid materials is described and validated in high-temperature laboratory experiments. The approach utilizes an ultrasound propagation path with naturally occurring or purposefully introduced echogenic features that partially redirect the energy of an ultrasound excitation pulse back to the transducer, resulting in a train of echoes. Their time of flight depends on the velocity of ultrasound propagation, which changes with temperature distribution in different segments of the propagation path. We reconstruct segmental temperature distributions under different parameterizations. Several parameterizations are discussed, including piecewise constant and piecewise linear, and the parametrization that requires that the estimated temperature profile satisfies an appropriate heat conduction model. The experimental validation of the proposed approach with an alumina sample shows that even with simple parameterizations, the temperature profile is correctly captured with an accuracy that may be comparable to that of the traditional pointwise sensors. The advantages of the approach are discussed, including its suitability for real time and non destructive temperature measurements in extreme environments and locations inaccessible to the traditional insertion sensors. PMID- 26678790 TI - Potential of ultrasonic pulse velocity for evaluating the dimensional stability of oak and chestnut wood. AB - The objective of this study was to examine the potential of ultrasonic velocity as a rapid and nondestructive method to predict the dimensional stability of oak (Quercus petraea (Mattuschka) Lieblein) and chestnut (Castanea sativa Mill.) that are commonly used in flooring industry. Ultrasonic velocity, specific gravity, and radial, tangential and volumetric shrinkages were measured on seventy-four 20*20*30-mm(3) specimens obtained from freshly cut oak and chestnut stems. The ultrasonic velocities of the specimens decreased with increasing moisture content (MC). We found that specific gravity was not a good predictor of the transverse shrinkages as indicated by relatively weak correlations. Ultrasonic velocity, on the other hand, was found to be a significant predictor of the transverse shrinkages for both oak and chestnut. The best results for prediction of shrinkages of oak and chestnut were obtained when the ultrasonic velocity and specific gravity were used together. The multiple regression models we developed in this study explained 77% of volumetric shrinkages in oak and 72% of volumetric shrinkages in chestnut. It is concluded that ultrasonic velocity coupled with specific gravity can be employed as predicting parameters to evaluate the dimensional stability of oak and chestnut wood during manufacturing process. PMID- 26678791 TI - Low Noncytotoxic Concentrations of 5-Fluorouracil Have No Adverse Effects on Maturation and Function of Bone Marrow-Derived Dendritic Cells in vitro: A Potentially Safe Adjuvant for Dendritic Cell-Based Cancer Therapy. AB - BACKGROUND: Low, noncytotoxic concentrations of various chemotherapeutic drugs like 5-fluorouracil (5-FU) induce antitumor immune responses by selectively depleting tumor-induced immunosuppressive cells, and could therefore be used in combination with dendritic cell (DC) vaccines in order to enhance their immunotherapeutic efficacy. However, the likely negative influences of low, noncytotoxic doses of 5-FU on bone marrow-derived (BM)-DCs in vitro have not yet been investigated. METHODS: The effects of low, noncytotoxic concentrations of 5 FU on mouse BM-DC differentiation and maturation markers (CD11c, MHC class II and CD80) as well as antigen-presenting capacity and cytokine production (IL-12p70 and IL-10) have been assessed. RESULTS: Different low doses of 5-FU had no significant effect on the expression of DC differentiation and maturation or on costimulatory markers (p = 0.5). Furthermore, suboptimal doses of 5-FU did not affect the immunostimulatory functions of DCs such as antigen presentation (p = 0.6) and cytokine production (p = 0.9). CONCLUSIONS: These data suggest that low doses of 5-FU have no adverse effects on DC maturation and function, and the efficacy of DC-based cancer immunotherapy may be greatly enhanced by combining it with suboptimal doses of 5-FU. PMID- 26678792 TI - Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland. AB - Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID- 26678793 TI - Examining the Effects of Stiffness and Mass Difference on the Thermal Interface Conductance Between Lennard-Jones Solids. AB - To date, the established methods that describe thermal interface conductance (TIC) and include mode-level dependence have not included anharmonicity. The current intuition is therefore based on the behavior in the harmonic limit, whereby the extent of overlap in the bulk phonon density of states (DoS) (e.g., frequency overlap) dictates the TIC and more frequency overlap leads to higher TIC. Here, we study over 2,000 interfaces described by the Lennard-Jones potential using equilibrium molecular dynamics simulations, whereby we systematically change the mass and stiffness of each side. We show that the trends in TIC do not generally follow that of the bulk phonon DoS overlap, but instead more closely follow the vibrational power spectrum overlap for the interfacial atoms. We then identify the frequency overlap in the interfacial power spectra as an improved descriptor for understanding the qualitative trends in TIC. Although improved, the results show that the basic intuition of frequency overlap is still insufficient to explain all of the features, as the remaining variations are shown to arise from anharmonicity, which is a critical effect to include in interface calculations above cryogenic temperatures. PMID- 26678794 TI - Vascular smooth muscle cell differentiation from human stem/progenitor cells. AB - Transplantation of vascular smooth muscle cells (VSMCs) is a promising cellular therapy to promote angiogenesis and wound healing. However, VSMCs are derived from diverse embryonic sources which may influence their role in the development of vascular disease and in its therapeutic modulation. Despite progress in understanding the mechanisms of VSMC differentiation, there remains a shortage of robust methods for generating lineage-specific VSMCs from pluripotent and adult stem/progenitor cells in serum-free conditions. Here we describe a method for differentiating pluripotent stem cells, such as embryonic and induced pluripotent stem cells, as well as skin-derived precursors, into lateral plate-derived VSMCs including 'coronary-like' VSMCs and neural crest-derived VSMC, respectively. We believe this approach will have broad applications in modeling origin-specific disease vulnerability and in developing personalized cell-based vascular grafts for regenerative medicine. PMID- 26678795 TI - An improved SELEX technique for selection of DNA aptamers binding to M-type 11 of Streptococcus pyogenes. AB - Streptococcus pyogenes is a clinically important pathogen consisting of various serotypes determined by different M proteins expressed on the cell surface. The M type is therefore a useful marker to monitor the spread of invasive S. pyogenes in a population. Serotyping and nucleic acid amplification/sequencing methods for the identification of M types are laborious, inconsistent, and usually confined to reference laboratories. The primary objective of this work is to develop a technique that enables generation of aptamers binding to specific M-types of S. pyogenes. We describe here an in vitro technique that directly used live bacterial cells and the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) strategy. Live S. pyogenes cells were incubated with DNA libraries consisting of 40-nucleotides randomized sequences. Those sequences that bound to the cells were separated, amplified using polymerase chain reaction (PCR), purified using gel electrophoresis, and served as the input DNA pool for the next round of SELEX selection. A specially designed forward primer containing extended polyA20/5Sp9 facilitated gel electrophoresis purification of ssDNA after PCR amplification. A counter-selection step using non-target cells was introduced to improve selectivity. DNA libraries of different starting sequence diversity (10(16) and 10(14)) were compared. Aptamer pools from each round of selection were tested for their binding to the target and non-target cells using flow cytometry. Selected aptamer pools were then cloned and sequenced. Individual aptamer sequences were screened on the basis of their binding to the 10 M-types that were used as targets. Aptamer pools obtained from SELEX rounds 5-8 showed high affinity to the target S. pyogenes cells. Tests against non-target Streptococcus bovis, Streptococcus pneumoniae, and Enterococcus species demonstrated selectivity of these aptamers for binding to S. pyogenes. Several aptamer sequences were found to bind preferentially to the M11 M-type of S. pyogenes. Estimated binding dissociation constants (Kd) were in the low nanomolar range for the M11 specific sequences; for example, sequence E-CA20 had a Kd of 7+/-1 nM. These affinities are comparable to those of a monoclonal antibody. The improved bacterial cell-SELEX technique is successful in generating aptamers selective for S. pyogenes and some of its M-types. These aptamers are potentially useful for detecting S. pyogenes, achieving binding profiles of the various M types, and developing new M-typing technologies for non-specialized laboratories or point-of-care testing. PMID- 26678796 TI - Fluorescent in situ hybridization for the localization of viruses, bacteria and other microorganisms in insect and plant tissues. AB - Methods for the localization of cellular components such as nucleic acids, proteins, cellular vesicles and more, and the localization of microorganisms including viruses, bacteria and fungi have become an important part of any research program in biological sciences that enable the visualization of these components in fixed and live tissues without the need for complex processing steps. The rapid development of microscopy tools and technologies as well as related fluorescent markers and fluorophores for many cellular components, and the ability to design DNA and RNA sequence-based molecular probes and antibodies which can be visualized fluorescently, have rapidly advanced this field. This review will focus on some of the localizations methods which have been used in plants and insect pests in agriculture, and other microorganisms, which are rapidly advancing the research in agriculture-related fields. PMID- 26678797 TI - ATP hydrolysis assists phosphate release and promotes reaction ordering in F1 ATPase. AB - F1-ATPase (F1) is a rotary motor protein that can efficiently convert chemical energy to mechanical work of rotation via fine coordination of its conformational motions and reaction sequences. Compared with reactant binding and product release, the ATP hydrolysis has relatively little contributions to the torque and chemical energy generation. To scrutinize possible roles of ATP hydrolysis, we investigate the detailed statistics of the catalytic dwells from high-speed single wild-type F1 observations. Here we report a small rotation during the catalytic dwell triggered by the ATP hydrolysis that is indiscernible in previous studies. Moreover, we find in freely rotating F1 that ATP hydrolysis is followed by the release of inorganic phosphate with low synthesis rates. Finally, we propose functional roles of the ATP hydrolysis as a key to kinetically unlock the subsequent phosphate release and promote the correct reaction ordering. PMID- 26678798 TI - [Operative therapy of spinal metastases from urological tumors]. AB - The treatment of bone metastases from urological tumors represents a palliative form of therapy, apart from the resection of solitary metastases from renal cell carcinomas. Due to the high incidence of spinal metastases this can result in clinically significant symptoms and possible complications for patients, such as pain, spinal instability and compression of the spinal canal with corresponding neurological deficits. By the use of targeted diagnostics and induction of radiotherapeutic and/or surgical treatment, for the majority of patients an immediate reduction in pain as well as early mobilization and sometimes even regression of existing neurological deficits and therefore an improved quality of life can be achieved. PMID- 26678799 TI - [Salvage lymphadenectomy in patients with prostate cancer recurrence: A review]. AB - BACKGROUND: Salvage extended pelvic lymph node dissection (salvage ePLND) in patients with prostate cancer (PCa) biochemical recurrence is an alternative to the commonly used androgen deprivation therapy (ADT) and/or chemotherapy. Small patient number, insufficient accuracy of contemporary imaging methods for lymph node relapse diagnostics, and the lack of prospective data present limiting factors for a wider application of salvage ePLND. The purpose of this publication is to review German and European data and studies on the subject of salvage ePLND and to discuss future perspectives. MATERIALS AND METHODS: We analyzed available studies up to October 2014 from Medline with the keywords "salvage lymph node dissection prostate cancer". RESULTS: A total of 51 publications since 1984 (up to October 2014) meeting the search criteria were found. Ten of these were studies that analyzed the results of salvage ePLND. Of these 10 studies, 6 originated from German clinics. Furthermore, among these 51 publications, there were 2 clinical case reports (1 from Germany) and 3 reviews (none from Germany). CONCLUSIONS: The available data show insufficient evidence-based validity. There have been no prospective studies and just one multicenter study. However, single center retrospective studies have shown promising results. Salvage ePLND leads to biochemical remission, freedom from clinical recurrence, and probably also to renewed response to ADT in patients with castration-resistant PCa. Multicenter prospective studies should be conducted in Germany (where most of the available studies have been performed). The selection of patients should be analyzed in order to identify clear selection criteria for salvage ePLND. PMID- 26678800 TI - Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid. AB - Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10MUM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2(*-) and H2O2, which correlated with increased levels of MnSOD activity and immuno reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96h indicating that as the cells became more differentiated, steady-state levels of H2O2 increased in the absence of increases in peroxide-scavenging antioxidants (i.e., glutathione, glutathione peroxidase, and catalase). In addition, ATRA induced stimulation of NF-M at 48 and 72h was enhanced by decreasing SOD activity using siRNA directed at MnSOD. Finally, treatment with ATRA for 96h in the presence of MnSOD siRNA or PEG-catalase inhibited ATRA induced increases in NF-M expression. These results provide strong support for the hypothesis that changes in steady-state levels of O2(*-) and H2O2 significantly contribute to the process of ATRA-induced differentiation in neuroblastoma, and suggest that retinoid therapy for neuroblastoma could potentially be enhanced by redox-based manipulations of superoxide metabolism to improve patient outcome. PMID- 26678801 TI - Selection maintaining protein stability at equilibrium. AB - The common understanding of protein evolution has been that neutral mutations are fixed by random drift, and a proportion of neutral mutations depending on the strength of structural and functional constraints primarily determines evolutionary rate. Recently it was indicated that fitness costs due to misfolded proteins are a determinant of evolutionary rate and selection originating in protein stability is a driving force of protein evolution. Here we examine protein evolution under the selection maintaining protein stability. Protein fitness is a generic form of fitness costs due to misfolded proteins; s=kappaexp(DeltaG/kT)(1-exp(DeltaDeltaG/kT)), where s and DeltaDeltaG are selective advantage and stability change of a mutant protein, DeltaG is the folding free energy of the wildtype protein, and kappa is a parameter representing protein abundance and indispensability. The distribution of DeltaDeltaG is approximated to be a bi-Gaussian distribution, which represents structurally slightly- or highly-constrained sites. Also, the mean of the distribution is negatively proportional to DeltaG. The evolution of this gene has an equilibrium point (DeltaGe) of protein stability, the range of which is consistent with observed values in the ProTherm database. The probability distribution of Ka/Ks, the ratio of nonsynonymous to synonymous substitution rate per site, over fixed mutants in the vicinity of the equilibrium shows that nearly neutral selection is predominant only in low-abundant, non-essential proteins of DeltaGe>-2.5 kcal/mol. In the other proteins, positive selection on stabilizing mutations is significant to maintain protein stability at equilibrium as well as random drift on slightly negative mutations, although the average is less than 1. Slow evolutionary rates can be caused by both high protein abundance/indispensability and large effective population size, which produces positive shifts of DeltaDeltaG through decreasing DeltaGe, and strong structural constraints, which directly make DeltaDeltaG more positive. Protein abundance/indispensability more affect evolutionary rate for less constrained proteins, and structural constraint for less abundant, less essential proteins. The effect of protein indispensability on evolutionary rate may be hidden by the variation of protein abundance and detected only in low-abundant proteins. Also, protein stability (-DeltaGe/kT) and are predicted to decrease as growth temperature increases. PMID- 26678802 TI - Effect of preoperative autologous blood donation on patients undergoing bimaxillary orthognathic surgery: a retrospective analysis. AB - The efficacy of preoperative autologous blood donation (PABD) was evaluated according to preoperative haemoglobin (Hb) values. The records of 295 patients who underwent bimaxillary orthognathic surgery between July 2007 and August 2008 were reviewed. The records for autologous blood donation, intraoperative transfusion, and related laboratory studies were also evaluated. The transfusion trigger used during this period was Hb < 10 g/dl. A total of 189 patients (64.1%) made a PABD and 106 patients (35.9%) did not. The incidence of allogeneic blood transfusion was significantly lower in the PABD group than in the no PABD group (15.9% vs. 29.2%, P = 0.007). This difference was greater in patients with a preoperative Hb < 14 g/dl (20.3% vs. 62.5%, P < 0.0001), and no difference was found in patients with Hb >= 14 g/dl (13.3% vs. 14.9%, P = 0.83). PABD reduced the incidence of allogeneic blood transfusion in patients undergoing bimaxillary orthognathic surgery, particularly in patients with a preoperative Hb < 14 g/dl. PABD could be used to reduce the frequency of intraoperative allogeneic blood transfusion in these patients. PMID- 26678803 TI - Prevention of falls in acute hospital settings: a multi-site audit and best practice implementation project. AB - OBJECTIVE: To assess falls prevention practices in Australian hospitals and implement interventions to promote best practice. DESIGN: A multi-site audit using eight evidence-based audit criteria. Following a baseline audit, barriers to compliance were identified and targeted. Two follow-up audit cycles assessed the sustainability of practice change. SETTING: Nine acute care hospitals around Australia, including a mix of public and private. One medical ward and one surgical ward from each hospital were involved. PARTICIPANTS: A clinical leader from each hospital, trained in evidence implementation, conducted the audits and implementation strategies in their setting. INTERVENTIONS: Multi-component falls prevention interventions were utilized, designed to target specific barriers to compliance identified at each hospital. Common interventions involved staff and patient education. MAIN OUTCOME MEASURE: Percentage compliance with falls prevention audit criteria and change in compliance between baseline and follow-up audits. Fall rate data were also analysed. RESULTS: Mean overall compliance at baseline across all hospitals was 50.4% (range 30.8-76.6%). At the first follow up, this had increased to 74.5% (range 59.4-87.4%), which was sustained at the second follow-up (74.1%, range 48.6-84.4%). There were no statistically significant differences between compliance rates in medical versus surgical wards or in private versus public hospitals. Despite sustained practice improvement, reported fall rates remained unchanged. The focus on staff education possibly led to improved reporting of falls, which may explain the apparent lack of effect on fall rates. CONCLUSIONS: Clinical audit and feedback is an effective strategy to promote quality improvement in falls prevention practices in acute hospital settings. PMID- 26678804 TI - Job satisfaction of urban community health workers after the 2009 healthcare reform in China: a systematic review. AB - PURPOSE: In 2009 China introduced a new round of healthcare reform to strengthen primary care networks through the development of Community Health Services (CHS). This study aimed to measure the degree of overall job satisfaction and also satisfaction dimensions and then find common causes of dissatisfaction among Community Health Workers (CHWs) in urban China by conducting a systematic review of relevant studies on CHWs' job satisfaction. DATA SOURCES: Web of Science, PubMed, Google scholar, Wanfangdata and CNKI were searched. STUDY SELECTION: Publications about job satisfaction of CHWs were screened and assessed. Finally 18 Chinese articles and 4 English articles were included. DATA EXTRACTION: Quantitative and qualitative data were extracted for nine themes concerning job satisfaction. Narrative synthesis was employed to analyze the data. RESULTS OF DATA SYNTHESIS: CHWs were generally neither satisfied nor dissatisfied with their work after 2009. Financial rewards and opportunities for professional development were the most important determinants of job dissatisfaction. Workers were generally satisfied with interpersonal relationships in the workplace. The expanded public health services package and human-resources related regulations, e.g. the professional rank promotion system, government-controlled staffing policy (i.e. staff-quota system) and government-controlled budgetary planning (i.e. the Separation of Revenue and Expenditure), were policies that had an effect on job satisfaction. CONCLUSION: Financial rewards and professional development were the two main predictors of job satisfaction. To improve CHS in China, policy-makers (especially the central government) need to consider the impact of current policies on job satisfaction in order to reduce job dissatisfaction. PMID- 26678805 TI - Associations between demographics and health-related quality of life for chronic non-malignant pain patients treated at a multidisciplinary pain centre: a cohort study. AB - OBJECTIVE: To describe the associations between demographics and health-related quality of life for chronic non-malignant pain patients. DESIGN: A cohort study. SETTING: A multidisciplinary Danish pain centre. STUDY PARTICIPANTS: All patients treated at the centre between 2007 and 2013. MAIN OUTCOME MEASURES: Levels of pain, anxiety and depression, and physical and mental status. The Hospital Anxiety and Depression Scale and the Medical Outcomes Study Short-Form Health Survey (SF-36) were used. RESULTS: A total of 1176 patients were included. The majority were women (64%), the mean age was 46.7 +/- 14.4 (range 18-89), and 21% were able to work full or part time. On a Numeric Rating Scale from 0 to 10, median pain-intensity was 8 (interquartile range 7-8) and pain-discomfort 8 (interquartile range 7-9) at time of referral. More than half of the patients had symptoms of anxiety and depression. Most of the individual SF-36 domains had median scores between 0 and 40 (Scale from 0 to 100). Patients younger than 50 years of age as well as patients on sick leave/disability pension had significantly lower SF-36 scores. Level of pain, anxiety and depression decreased and SF-36-scores increased significantly after a course of treatment which in most cases consisted of both medical, physiotherapeutic and psychological treatment as well as health-oriented education. The chi-square test, Mann-Whitney U-test, the Kruskal-Wallis and Wilcoxon Signed-rank test were used for analyses. CONCLUSIONS: In order to improve treatment at a multidisciplinary pain centre, it may be of value to target treatments to different patient subgroups based on, amongst other things, age and employment status. PMID- 26678806 TI - Reproducibility and conflicts in immune epitope data. AB - The Immune Epitope Database is uniquely positioned to assess the body of research related to immune epitopes, we have manually curated all such published data. Thus, we are able to make observations on the state of these fields of research, as well as aggregate the individual data points to present a clearer picture of the immune response to specific antigens in all studied hosts. Additionally, we are able to identify where conflicts in the literature exist and where publications fall short in terms of identifiable methods and in reproducibility. Here we present guidelines to improve the quality of immune epitope data, which will benefit journals and researchers alike. PMID- 26678808 TI - Epigenetics: Weight change alters the spermatozoal epigenome. PMID- 26678810 TI - Maternal thyroid function in pregnancy - a tale of two tails. PMID- 26678807 TI - Endocannabinoids--at the crossroads between the gut microbiota and host metabolism. AB - Various metabolic disorders are associated with changes in inflammatory tone. Among the latest advances in the metabolism field, the discovery that gut microorganisms have a major role in host metabolism has revealed the possibility of a plethora of associations between gut bacteria and numerous diseases. However, to date, few mechanisms have been clearly established. Accumulating evidence indicates that the endocannabinoid system and related bioactive lipids strongly contribute to several physiological processes and are a characteristic of obesity, type 2 diabetes mellitus and inflammation. In this Review, we briefly define the gut microbiota as well as the endocannabinoid system and associated bioactive lipids. We discuss existing literature regarding interactions between gut microorganisms and the endocannabinoid system, focusing specifically on the triad of adipose tissue, gut bacteria and the endocannabinoid system in the context of obesity and the development of fat mass. We highlight gut-barrier function by discussing the role of specific factors considered to be putative 'gate keepers' or 'gate openers', and their role in the gut microbiota endocannabinoid system axis. Finally, we briefly discuss data related to the different pharmacological strategies currently used to target the endocannabinoid system, in the context of cardiometabolic disorders and intestinal inflammation. PMID- 26678811 TI - Pregnancy: Maternal obesity affects neonatal adipogenesis. PMID- 26678809 TI - Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. AB - Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin- resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin-angiotensin aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies. PMID- 26678812 TI - Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions. AB - BACKGROUND: Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. On the other hand, other studies reported normal serum homocysteine levels. OBJECTIVES: Our aim was to study the Hcy level in active vitiligo patients both in serum and in suction blister fluid obtained from the lesional skin. METHOD: A total of 30 patients with active vitiligo of both sexes and 30 healthy volunteers were enrolled in this study. Sera from the blood and from lesional induced bullae were obtained from the patients and controls and were assayed for Hcy by enzyme-linked immunosorbent assay (ELISA). The collected data were analyzed by SPSS version 17. RESULTS: There were no significant differences in the serum levels of Hcy between patients and healthy controls, however, the increase in Hcy level was highly statistically significant in the patients' lesional induced bulla compared to the healthy controls. There was no significant difference in Hcy levels between males and females and between patients with negative or positive family histories of vitiligo. CONCLUSION: The presence of a high homocysteine level in active vitiligo lesions points to a local event occurring in this lesion, which is not reflected as an increase in the patient's serum level. PMID- 26678813 TI - BMPs in bone regeneration: Less is more effective, a paradigm-shift. AB - Worldwide, the clinical application of BMP2 (bone morphogenetic protein 2) has helped an increasing number of patients achieve bone regeneration in a clinical area lacking simple solutions for difficult bone healing situations. In this review, the historical aspects and current critical clinical issues are summarized and positioned against new research findings on efficacy and function of BMP2. Knowledge concerning how the dose of this growth factor as well as its interaction with mechanical loading influences the efficacy of bone regeneration, might open possible future strategies in cases where bony bridging is unachievable so far. In conclusion, it is apparent that there is a substantial need for continued basic research to unravel the details of its function and the underlying signaling pathways involved, to make BMP2 even more relevant and safe in daily clinical use, even though this growth factor has been known for more than 125 years. PMID- 26678815 TI - Toward Interoperability: A New Resource to Support Nursing Terminology Standards. PMID- 26678814 TI - Mechanisms of action of bone morphogenetic proteins in cancer. AB - The bone morphogenetic proteins (BMPs) play fundamental roles in embryonic development and control differentiation of a diverse set of cell types. It is therefore of no surprise that the BMPs also contribute to the process of tumourigenesis and regulate cancer progression through various stages. We summarise here key roles of BMP ligands, receptors, their signalling mediators, mainly focusing on proteins of the Smad family, and extracellular antagonists, that contribute to the onset of tumourigenesis and to cancer progression in diverse tissues. Overall, the BMP pathways seem to act as tumour suppressors that maintain physiological tissue homeostasis and which are perturbed in cancer either via genetic mutation or via epigenetic misregulation of key gene components. BMPs also control the self-renewal and fate choices made by stem cells in several tissues. By promoting cell differentiation, including inhibition of the process of epithelial-mesenchymal transition, BMPs contribute to the malignant progression of cancer at advanced stages. It is therefore reasonable that pharmaceutical industries continuously develop biological agents and chemical modulators of BMP signalling with the aim to improve therapeutic regimes against several types of cancer. PMID- 26678816 TI - ANI Emerging Leaders Project: Nurses' Perceptions of the Use of Health Information Technology Tools for Patient and Family Engagement. PMID- 26678818 TI - Principal component analysis for designed experiments. AB - BACKGROUND: Principal component analysis is used to summarize matrix data, such as found in transcriptome, proteome or metabolome and medical examinations, into fewer dimensions by fitting the matrix to orthogonal axes. Although this methodology is frequently used in multivariate analyses, it has disadvantages when applied to experimental data. First, the identified principal components have poor generality; since the size and directions of the components are dependent on the particular data set, the components are valid only within the data set. Second, the method is sensitive to experimental noise and bias between sample groups. It cannot reflect the experimental design that is planned to manage the noise and bias; rather, it estimates the same weight and independence to all the samples in the matrix. Third, the resulting components are often difficult to interpret. To address these issues, several options were introduced to the methodology. First, the principal axes were identified using training data sets and shared across experiments. These training data reflect the design of experiments, and their preparation allows noise to be reduced and group bias to be removed. Second, the center of the rotation was determined in accordance with the experimental design. Third, the resulting components were scaled to unify their size unit. RESULTS: The effects of these options were observed in microarray experiments, and showed an improvement in the separation of groups and robustness to noise. The range of scaled scores was unaffected by the number of items. Additionally, unknown samples were appropriately classified using pre arranged axes. Furthermore, these axes well reflected the characteristics of groups in the experiments. As was observed, the scaling of the components and sharing of axes enabled comparisons of the components beyond experiments. The use of training data reduced the effects of noise and bias in the data, facilitating the physical interpretation of the principal axes. CONCLUSIONS: Together, these introduced options result in improved generality and objectivity of the analytical results. The methodology has thus become more like a set of multiple regression analyses that find independent models that specify each of the axes. PMID- 26678819 TI - Color properties of the motion detectors projecting to the goldfish tectum. AB - Interactions between color channels (long-wave (L), middle-wave (M) and short wave (S)) in the receptive field of direction-selective (DS) and orientation selective (OS) ganglion cells (GCs) were investigated with combined selective stimulation of pairs of cone types (L and M, L and S, M and S). In the experiments with DS GCs of both ON and OFF types, it was shown that: (1) M and S channels were synergistic relative to each other and opponent to L channel. (2) Three-parameter signal (from L, M and S cones) is transformed to one-parameter signal at the output of DS GC, thus illustrating the principle of univariance. (3) In the experiments with OS GCs, it was shown that L and M channels were synergistic in the OFF-pathway, while the S channel was opponent to them. Our results suggested that photoreceptor synaptic connectivity of the bipolar cells hypothetically involved in the goldfish OS circuitry substantially differs from connectivity of bipolar cells presumably targeting DS GC. (4) To sum up, the results obtained on DS GCs confirmed the plausibility of proposed DS GC wiring diagrams; as to the OS circuitry of fish retina it still remains unclear and needs further investigation. PMID- 26678820 TI - Perception adapts via top-down regulation to task repetition: A Lotka-Volterra Haken modeling analysis of experimental data. AB - Two experiments are reported in which participants perceived different physical quantities: size and speed. The perceptual tasks were performed in the context of motor performance problems. Participants perceived the size of objects in order to grasp the objects single handed or with both hands. Likewise, participants perceived the speed of a moving treadmill in order to control walking or running at that speed. In both experiments, the perceptual tasks were repeatedly performed by the participants while the to-be-perceived quantity was gradually varied from small to large objects (Experiment 1) and from low to high speeds (Experiment 2). Hysteresis with negative sign was found when participants were not allowed to execute the motor component, that is, when the execution stage was decoupled from the planning stage. No such effect was found in the control condition, when participants were allowed to execute the motor action. Using a Lotka-Volterra-Haken model for two competing neural populations, it is argued that the observations are consistent with the notion that the repetitions induce an adaptation effect of the perceptual system via top-down regulation. Moreover, the amount of synaptic modulation involved in the adaptation is estimated from participant data. PMID- 26678821 TI - Multivariable analysis to determine if HIV-1 Tat dicysteine motif is associated with neurodevelopmental delay in HIV-infected children in Malawi. AB - BACKGROUND: HIV-1 Tat protein is implicated in HIV-neuropathogenesis. Tat C31S polymorphism (Tat(CS)) has been associated with milder neuropathology in vitro and in animal models but this has not been addressed in a cohort of HIV-infected adults or children. METHODS: HIV viral load (VL) in plasma and cerebrospinal fluid (CSF) were determined and plasma HIV tat gene was sequenced. Neurodevelopmental assessment was performed using Bayley Scales of Infant Development III (BSID-III), with scores standardized to Malawian norms. The association between Tat(CS) and BSID-III scores was evaluated using multivariate linear regression. RESULTS: Neurodevelopmental assessment and HIV tat genotyping were available for 33 children. Mean age was 19.4 (SD 7.1) months, mean log VL was 5.9 copies/mL (SD 0.1) in plasma and 3.9 copies/mL (SD 0.9) in CSF. The prevalence of Tat(CC) was 27 %. Z-scores for BSID-III subtests ranged from -1.3 to -3.9. Tat(CC) was not associated with higher BSID-III z-scores. CONCLUSIONS: The hypothesis of milder neuropathology in individuals infected with HIV Tat(CS) was not confirmed in this small cohort of Malawian children. Future studies of tat genotype and neurocognitive disorder should be performed using larger sample sizes and investigate if this finding is due to differences in HIV neuropathogenesis between children and adults. PMID- 26678822 TI - Microbial causes of complicated acute bacterial rhinosinusitis and implications for empirical antimicrobial therapy. AB - OBJECTIVES: Very little up-to-date information is available on the microbiology of complicated acute bacterial rhinosinusitis. Reliable microbiology testing is necessary to inform current empirical antimicrobial treatments. This study was conducted in response to recent US guidelines on antimicrobial treatments for acute bacterial rhinosinusitis. It aimed to describe the pathological micro organisms involved in complicated acute bacterial rhinosinusitis in the UK and their antimicrobial susceptibility. METHODS: This study collected retrospective data on cases of complicated acute bacterial rhinosinusitis with sinogenic orbital and/or intracranial infections from 2007 to 2012. Bacteria identified in paranasal sinus pus were compared with those identified in orbital and/or intracranial infections. RESULTS: Streptococcus anginosus group bacteria were isolated from 61.3 per cent of paranasal sinus pus samples, 83.3 per cent of orbital infections and 77.8 per cent of intracranial infections. All S anginosus isolates were sensitive to penicillin; no penicillin-resistant organisms were isolated. CONCLUSION: S anginosus was the predominant organism isolated from complicated acute bacterial rhinosinusitis samples at our UK centre. S anginosus is sensitive to penicillin, suggesting that penicillin can be used as an appropriate first-line empirical antibiotic for uncomplicated acute bacterial rhinosinusitis. PMID- 26678823 TI - Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review. AB - Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. PMID- 26678824 TI - Relationship between postnatal weight and premature retinopathy in Guatemala. PMID- 26678825 TI - Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model. AB - An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation. PMID- 26678826 TI - How genome complexity can explain the difficulty of aligning reads to genomes. AB - BACKGROUND: Although it is frequently observed that aligning short reads to genomes becomes harder if they contain complex repeat patterns, there has not been much effort to quantify the relationship between complexity of genomes and difficulty of short-read alignment. Existing measures of sequence complexity seem unsuitable for the understanding and quantification of this relationship. RESULTS: We investigated several measures of complexity and found that length sensitive measures of complexity had the highest correlation to accuracy of alignment. In particular, the rate of distinct substrings of length k, where k is similar to the read length, correlated very highly to alignment performance in terms of precision and recall. We showed how to compute this measure efficiently in linear time, making it useful in practice to estimate quickly the difficulty of alignment for new genomes without having to align reads to them first. We showed how the length-sensitive measures could provide additional information for choosing aligners that would align consistently accurately on new genomes. CONCLUSIONS: We formally established a connection between genome complexity and the accuracy of short-read aligners. The relationship between genome complexity and alignment accuracy provides additional useful information for selecting suitable aligners for new genomes. Further, this work suggests that the complexity of genomes sometimes should be thought of in terms of specific computational problems, such as the alignment of short reads to genomes. PMID- 26678827 TI - Developing high strength and ductility in biomedical Co-Cr cast alloys by simultaneous doping with nitrogen and carbon. AB - There is a strong demand for biomedical Co-Cr-based cast alloys with enhanced mechanical properties for use in dental applications. We present a design strategy for development of Co-Cr-based cast alloys with very high strength, comparable to that of wrought Co-Cr alloys, without loss of ductility. The strategy consists of simultaneous doping of nitrogen and carbon, accompanied by increasing of the Cr content to increase the nitrogen solubility. The strategy was verified by preparing Co-33Cr-9W-0.35N-(0.01-0.31)C (mass%) alloys. We determined the carbon concentration dependence of the microstructures and their mechanical properties. Metal ion release of the alloys in an aqueous solution of 0.6% sodium chloride (NaCl) and 1% lactic acid was also evaluated to ensure their corrosion resistance. As a result of the nitrogen doping, the formation of a brittle sigma-phase, a chromium-rich intermetallic compound, was significantly suppressed. Adding carbon to the alloys resulted in finer-grained microstructures and carbide precipitation; accordingly, the strength increased with increasing carbon concentration. The tensile ductility, on the other hand, increased with increasing carbon concentration only up to a point, reaching a maximum at a carbon concentration of ~0.1mass% and decreasing with further carbon doping. However, the alloy with 0.31mass% of carbon exhibited 14% elongation and also possessed very high strength (725MPa in 0.2% proof stress). The addition of carbon did not significantly degrade the corrosion resistance. The results show that our strategy realizes a novel high-strength Co-Cr-based cast alloy that can be produced for advanced dental applications using a conventional casting procedure. STATEMENT OF SIGNIFICANCE: The present study suggested a novel alloy design concept for realizing high-strength Co-Cr-based cast alloys. The proposed strategy is beneficial from the practical point of view because it uses conventional casting approach-a simpler, more cost-effective, industrially friendly manufacturing process than other manufacturing processes such as thermomechanical processing or powder metallurgy. The developed alloys showed the excellent strength-ductility balance and significantly high strength comparable to that of wrought Co-Cr-Mo alloys, while maintaining acceptable ductility and good corrosion resistance. We described the relationship between microstructures and mechanical and corrosion prosperities of the developed alloys; this provides the fundamental aspect of the proposed strategy and will be helpful for further investigations or industrial realization of the proposed strategy. PMID- 26678828 TI - Revival of nitrogen-containing bisphosphonate-induced inhibition of osteoclastogenesis and osteoclast function by water-soluble microfibrous borate glass. AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious skeletal complication associated with the long-term oral or intravenous use of nitrogen containing bisphosphonates (N-BPs). Here, we investigated the effects of an ionic cocktail prepared from water-soluble microfibrous borate glass on neutralizing the inhibitory effects of two heterocyclic N-BPs, risedronate or zoledronic acid, on osteoclastogenesis, apoptosis of differentiated osteoclasts and osteoclast function. Cell growth and proliferation assays were first performed on RAW 264.7 cells to optimize the concentrations of the ionic cocktail and N-BPs to be used for static cell culture. The pre-osteoclasts were then stimulated with RANKL to differentiate into osteoclasts. The effects of the ionic cocktail and N-BPs on osteoclast differentiation, apoptosis and function were subsequently examined using 3 series of experiments conducted at the gene, protein, morphological and functional levels. After concentration optimization, the ionic cocktail was found to partially reverse N-BP-induced inhibition of osteoclastogenesis, stimulation of osteoclasts apoptosis and reduction of osteoclast resorptive activity. Ultrastructural examination of osteoclasts that had been exposed to either N-BP identified classical features of late apoptosis and secondary necrosis, while osteoclasts exposed simultaneously to the concentration-optimized ionic cocktail and N-BPs exhibited only signs of early apoptosis that were possibly reversible. Taken together, the results of the 4 series of experiments indicate that the ionic cocktail produced from dissolution of borate glass dressings has the potential to rescue the adverse effects of heterocyclic N-BPs on osteoclast differentiation and function. These results warrant further confirmation using dynamic cell culture and small animal BRONJ models. STATEMENT OF SIGNIFICANCE: Long-term oral and intravenous use of nitrogen-containing bisphosphonates (N-BPs) may result in bisphosphonate-related osteonecrosis of the jaw (BRONJ) due to the suppression of normal bone turnover. There is no effective treatment for such a complication to date. This work reported the use of an ionic cocktail derived from water-soluble microfibrous borate glass to revert heterocyclic N-BP-induced inhibition of osteoclastogenesis, stimulation of osteoclasts apoptosis and reduction of osteoclasts resorption in static cell culture condition. This ionic cocktail may have the potential to be further developed into a new adjunctive treatment for BRONJ. PMID- 26678829 TI - Cortisol regulates sodium homeostasis by stimulating the transcription of sodium chloride transporter (NCC) in zebrafish (Danio rerio). AB - In mammals, sodium/hydrogen exchanger (NHE) and sodium-chloride cotransporter (NCC) are expressed in renal tubules, and exhibit functional redundancy and mutual compensation in Na(+) uptake. In teleosts, the gills of the adult and skin of the embryonic stage function as external kidneys, and ionocytes are responsible for ionoregulation in these tissues. NHE- and NCC-expressing ionocytes mutually cooperate to adjust Na(+) uptake, which is analogous to the activity of the mammalian kidney. Cortisol is a hormone that controls Na(+) uptake through regulating NCC expression and activity in mammals; however, cortisol-mediated control of NCC expression is little understood in non-mammalian vertebrates, such as teleosts. It is essential for our understanding of the evolution of such regulation to determine whether cortisol has a conserved effect on NCC in vertebrates. In the present study, we treated zebrafish embryos with low Na(+) medium (LNa, 0.04 mM Na(+)) for 3 d to stimulate the mRNA expression of nhe3b, ncc, and cyp11b1 (a cortisol-synthesis enzyme) and whole body cortisol level. Exogenous cortisol treatment (20 mg/l, 3 d) resulted in an elevation of whole-body Na(+) content, ncc expression, and the density of ncc-expressing cells in zebrafish larvae. In loss-of-function experiments, microinjection of glucocorticoid receptor (gr) morpholino (MO) suppressed sodium content, ncc expression, and the density of ncc-expressing cells, but injection of mr MO had no such effects. In addition, exogenous cortisol treatment and gr MO injection also altered ncc expression and the density of ncc-expressing cells in gcm2 morphant larvae. Taken together, cortisol and GR appear to regulate Na(+) absorption through stimulating ncc expression and the differentiation of ncc expressing ionocytes, providing new insights into the actions of cortisol on Na(+) uptake. PMID- 26678831 TI - Keep Your Career Fresh. PMID- 26678833 TI - Recap 2015. PMID- 26678834 TI - The complete chloroplast genome of the southern Chinese pine Pinus tabuliformis (Pinales: Pinaceae). AB - The complete nucleotide sequence of Pinus tabuliformis chloroplast genome (cpDNA) was carried out using Illumina Hiseq 2500. The genome is 119 646 bp in length, and the overall base composition of H-strand is 30.6% for A, 19.3% for C, 19.2% for G and 30.9% for T. There are 116 genes in the cpDNA, including 74 protein coding genes, four ribosomal RNA genes (four rRNA species), and 36 transfer RNA genes (20 tRNA species). Phylogenetic analyses of P. tabuliformis and other 12 species belonging to Pinales were carried out using MEGA 6.0 with Neighbor Joining methods. The sequences of P. tabuliformis were clustered in subfamily Pinaceae. PMID- 26678830 TI - Mouse models of adrenocortical tumors. AB - The molecular basis of the organogenesis, homeostasis, and tumorigenesis of the adrenal cortex has been the subject of intense study for many decades. Specifically, characterization of tumor predisposition syndromes with adrenocortical manifestations and molecular profiling of sporadic adrenocortical tumors have led to the discovery of key molecular pathways that promote pathological adrenal growth. However, given the observational nature of such studies, several important questions regarding the molecular pathogenesis of adrenocortical tumors have remained. This review will summarize naturally occurring and genetically engineered mouse models that have provided novel tools to explore the molecular and cellular underpinnings of adrenocortical tumors. New paradigms of cancer initiation, maintenance, and progression that have emerged from this work will be discussed. PMID- 26678838 TI - EprS, an autotransporter serine protease, plays an important role in various pathogenic phenotypes of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa possesses an arsenal of both cell-associated (flagella, pili, alginate, etc.) and extracellular (exotoxin A, proteases, type III secretion effectors, etc.) virulence factors. Among them, secreted proteases that damage host tissues are considered to play an important role in the pathogenesis of P. aeruginosa infections. We previously reported that EprS, an autotransporter protease of P. aeruginosa, induces host inflammatory responses through protease activated receptors. However, little is known about the role of EprS as a virulence factor of P. aeruginosa. In this study, to investigate whether EprS participates in the pathogenicity of P. aeruginosa, we characterized various pathogenic phenotypes of the wild-type PAO1 strain and its eprS-disrupted mutant. The growth assays demonstrated that the growth of the eprS mutant was somewhat lower than that of the wild-type strain in a minimal medium containing BSA as the sole carbon and nitrogen source. Thus, these results indicate that eprS would have a role in the growth of P. aeruginosa in the presence of limited nutrients, such as a medium containing proteinaceous materials as a sole nutrient source. Furthermore, disruption of eprS resulted in a decreased production of elastase, pigments, autoinducers and surfactants, and a reduction of swimming and swarming motilities. In addition, the eprS mutant exhibited a reduction in the ability to associate with A549 cells and an attenuation of virulence in leucopenic mice as compared with the wild-type strain. Collectively, these results suggest that EprS exerts pleiotropic effects on various pathogenic phenotypes of P. aeruginosa. PMID- 26678835 TI - Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post pandemic influenza seasons, 2010/11-2012/13. AB - BACKGROUND: Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. METHODS: We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. RESULTS: A total of 24/7/20 influenza associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80% had influenza A, including 65% with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6-11.0). The most frequent diagnoses were influenza-associated pneumonia (62%), bronchitis/bronchiolitis (32%), secondary bacterial pneumonia (26 %), and ARDS (21%). Thirty-six patients (77 %) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1-11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2%) extracorporeal membrane oxygenation; 19% were treated with oseltamivir. Five children (11%) had pulmonary sequelae. Five children (11%) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). CONCLUSIONS: Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany. PMID- 26678839 TI - Investigation on the effect of fluorescence quenching of bovine serum albumin by cefoxitin sodium using fluorescence spectroscopy and synchronous fluorescence spectroscopy. AB - The reaction mechanism of cefoxitin sodium with bovine serum albumin was investigated using fluorescence spectroscopy and synchronous fluorescence spectroscopy at different temperatures. The results showed that the change of binding constant of the synchronous fluorescence method with increasing temperature could be used to estimate the types of quenching mechanisms of drugs with protein and was consistent with one of fluorescence quenching method. In addition, the number of binding sites, type of interaction force, cooperativity between drug and protein and energy-transfer parameters of cefoxitin sodium and bovine serum albumin obtained from two methods using the same equation were consistent. Electrostatic force played a major role in the conjugation reaction between bovine serum albumin and cefoxitin sodium, and the type of quenching was static quenching. The primary binding site for cefoxitin sodium was sub hydrophobic domain IIA, and the number of binding sites was 1. The value of Hill's coefficients (nH ) was approximately equal to 1, which suggested no cooperativity in the bovine serum albumin-cefoxitin sodium system. The donor-to acceptor distance r < 7 nm indicated that static fluorescence quenching of bovine serum albumin by cefoxitin sodium was also a non-radiation energy-transfer process. The results indicated that synchronous fluorescence spectrometry could be used to study the reaction mechanism between drug and protein, and was a useful supplement to the conventional method. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26678836 TI - Genome-wide transcriptome analyses of developing seeds from low and normal phytic acid soybean lines. AB - BACKGROUND: Low phytic acid (lpa) crops are potentially eco-friendly alternative to conventional normal phytic acid (PA) crops, improving mineral bioavailability in monogastric animals as well as decreasing phosphate pollution. The lpa crops developed to date carry mutations that are directly or indirectly associated with PA biosynthesis and accumulation during seed development. These lpa crops typically exhibit altered carbohydrate profiles, increased free phosphate, and lower seedling emergence, the latter of which reduces overall crop yield, hence limiting their large-scale cultivation. Improving lpa crop yield requires an understanding of the downstream effects of the lpa genotype on seed development. Towards that end, we present a comprehensive comparison of gene-expression profiles between lpa and normal PA soybean lines (Glycine max) at five stages of seed development using RNA-Seq approaches. The lpa line used in this study carries single point mutations in a myo-inositol phosphate synthase gene along with two multidrug-resistance protein ABC transporter genes. RESULTS: RNA sequencing data of lpa and normal PA soybean lines from five seed-developmental stages (total of 30 libraries) were used for differential expression and functional enrichment analyses. A total of 4235 differentially expressed genes, including 512-transcription factor genes were identified. Eighteen biological processes such as apoptosis, glucan metabolism, cellular transport, photosynthesis and 9 transcription factor families including WRKY, CAMTA3 and SNF2 were enriched during seed development. Genes associated with apoptosis, glucan metabolism, and cellular transport showed enhanced expression in early stages of lpa seed development, while those associated with photosynthesis showed decreased expression in late developmental stages. The results suggest that lpa causing mutations play a role in inducing and suppressing plant defense responses during early and late stages of seed development, respectively. CONCLUSIONS: This study provides a global perspective of transcriptomal changes during soybean seed development in an lpa mutant. The mutants are characterized by earlier expression of genes associated with cell wall biosynthesis and a decrease in photosynthetic genes in late stages. The biological processes and transcription factors identified in this study are signatures of lpa-causing mutations. PMID- 26678837 TI - Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database. AB - BACKGROUND: Epilepsy is a serious condition which can profoundly affect an individual's life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. METHODS: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox's proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. RESULTS: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). CONCLUSIONS: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies. PMID- 26678840 TI - Extremely low genetic diversity of mtDNA control region and remarkable population differentiation of Ichthyophis bannanicus (Amphibia: Gymnophiona). AB - It is widely accepted that the mitochondrial DNA (mtDNA) control region (CR) gene evolves more quickly than protein-encoding genes, such as ND2 and Cyt b, with few exceptions. However, some species have a different evolution pattern. In the present study, we sequenced the mtDNA CR partial sequences (454 base pairs) of 142 individuals from five sampling sites of Ichthyophis bannanicus and compared the genetic diversity and structure with the information from the NADH dehydrogenase subunit 2 (ND2) and Cytochrome b (Cyt b) genes within this species. Extremely low genetic diversity was found in the mtDNA CR compared with those of the ND2 and Cyt b genes. These results showed that the relatively mean clock rate of the CR was broadly lower than those of the ND2 (about 2.55 times) and Cyt b (about 3.14 times) genes. Despite the extremely low genetic diversity of CR, the population structure analysis identified two groups, Xishuangbanna and Northern Vietnam-Yulin-Yangchun-Deqing, which indicated that the Red River systems may have acted as gene-flow barriers for I. bannanicus. PMID- 26678842 TI - Common long-term complications of adult congenital heart disease: avoid falling in a H.E.A.P. AB - Advances in cardiology and cardiac surgery have transformed the outlook for patients with congenital heart disease (CHD) so that currently 85% of neonates with CHD survive into adult life. Although early surgery has transformed the outcome of these patients, it has not been curative. Heart failure, endocarditis, arrhythmias and pulmonary hypertension are the most common long term complications of adults with CHD. Adults with CHD benefit from tertiary expert care and early recognition of long-term complications and timely management are essential. However, it is as important that primary care physicians and general adult cardiologists are able to recognise the signs and symptoms of such complications, raise the alarm, referring patients early to specialist adult congenital heart disease (ACHD) care, and provide initial care. In this paper, we provide an overview of the most commonly encountered long-term complications in ACHD and describe current state of the art management as provided in tertiary specialist centres. PMID- 26678841 TI - Neuroregression as an initial manifestation in a toddler with acquired pernicious anaemia. AB - The aetiology spectrum for neuroregression in infants and toddlers is diverse. Vitamin B12 deficiency-mediated neuroregression is less commonly considered as a differential. Prevalence of pernicious anaemia in the general population is 0.1% and is extremely rare in children. We describe a 35-month-old toddler with neuroregression, seizures, coarse tremors, bleating cry and neuropathy. His clinical symptomatology mimicked grey matter degenerative illness and infantile tremor syndrome, a nutritional deficiency-mediated movement disorder. His vitamin B12 level was low and serum homocysteine level was elevated. Haematological manifestations were not overt and anti-intrinsic factor antibody was positive. With parenteral vitamin B12 therapy, there was a dramatic response with clinical and laboratory translation. This report emphasises the need for a high index of suspicion and screening for markers of vitamin B12 deficiency in all children with unexplained acute or subacute neuroregression, seizures and movement disorders as it is potentially reversible. PMID- 26678843 TI - Bottom-Up Preparation of Ultrathin 2D Aluminum Oxide Nanosheets by Duplicating Graphene Oxide. AB - 2D ultrathin aluminum oxide (2D-Al2O3) nanosheets are prepared by duplicating graphene oxide. An amorphous precursor of the hydroxide of aluminum is first deposited onto graphene oxide sheets, which are then converted into 2D-Al2 O3 nanosheets by calcination, while the graphene oxide is removed. The 2D-Al2O3 nanosheets have a large specific surface area and a superior adsorption capacity to fluoride ions. PMID- 26678844 TI - Readiness potentials driven by non-motoric processes. AB - An increase in brain activity known as the "readiness potential" (RP) can be seen over central scalp locations in the seconds leading up to a volitionally timed movement. This activity precedes awareness of the ensuing movement by as much as two seconds and has been hypothesized to reflect preconscious planning and/or preparation of the movement. Using a novel experimental design, we teased apart the relative contribution of motor-related and non-motor-related processes to the RP. The results of our experiment reveal that robust RPs occured in the absence of movement and that motor-related processes did not significantly modulate the RP. This suggests that the RP measured here is unlikely to reflect preconscious motor planning or preparation of an ensuing movement, and instead may reflect decision-related or anticipatory processes that are non-motoric in nature. PMID- 26678845 TI - Bubble-Pen Lithography. AB - Current lithography techniques, which employ photon, electron, or ion beams to induce chemical or physical reactions for micro/nano-fabrication, have remained challenging in patterning chemically synthesized colloidal particles, which are emerging as building blocks for functional devices. Herein, we develop a new technique - bubble-pen lithography (BPL) - to pattern colloidal particles on substrates using optically controlled microbubbles. Briefly, a single laser beam generates a microbubble at the interface of colloidal suspension and a plasmonic substrate via plasmon-enhanced photothermal effects. The microbubble captures and immobilizes the colloidal particles on the substrate through coordinated actions of Marangoni convection, surface tension, gas pressure, and substrate adhesion. Through directing the laser beam to move the microbubble, we create arbitrary single-particle patterns and particle assemblies with different resolutions and architectures. Furthermore, we have applied BPL to pattern CdSe/ZnS quantum dots on plasmonic substrates and polystyrene (PS) microparticles on two-dimensional (2D) atomic-layer materials. With the low-power operation, arbitrary patterning and applicability to general colloidal particles, BPL will find a wide range of applications in microelectronics, nanophotonics, and nanomedicine. PMID- 26678847 TI - A case of spontaneous bile leak. PMID- 26678848 TI - Acrylamide elution from roasted barley grains into mugicha and its formation during roasting. AB - This paper investigated acrylamide elution from roasted barley grain into mugicha and its formation during roasting of the grain. Mugicha is an infusion of roasted barley grains. Highly water-soluble acrylamide was easily extracted to mugicha from milled roasted barley grains in teabags. On the other hand, the acrylamide concentration in mugicha prepared from loose grain increased with longer simmering and steeping times. During roasting in a drum roaster, the acrylamide concentration of the grain increased as the surface temperature rose, reaching a maximum at 180-240 degrees C. Above this temperature, the acrylamide concentration decreased with continued roasting, exhibiting an inverted 'U' shaped curve. For most of the samples, the acrylamide concentration showed good correlation with the value of the colour space parameter L*. The dark-coloured roasted barley grains with lower L* values contained lower amounts of acrylamide as a result of deep roasting. The level of asparagine in barley grains was found to be a significant factor related to acrylamide formation in roasted barley products. The data are an important contribution to the mitigation of acrylamide intake from mugicha. PMID- 26678846 TI - Bariatric surgery improves female pelvic floor disorders. AB - OBJECTIVES: Obesity aggravates pelvic floor disorders in women. Weight loss improves these disorders. The purpose of this study was to assess the evolution of pelvic floor disorders in women who have undergone bariatric surgery. PATIENTS AND METHODS: A prospective single-center study was conducted from December 2012 to February 2014. The parameters studied were diabetes, BMI, excess weight loss, multiparity, mode of delivery and their relation to obesity and pelvic floor disorders. We evaluated anorectal and urethral sphincter disorders using the PFDI 20 questionnaire preoperatively, at 1 month and then every 6 months thereafter. RESULTS: One hundred and sixteen patients underwent bariatric surgery. Seventy questionnaires were completed preoperatively and postoperatively. Weight loss was significant with an excess weight loss of 57.1%. The mean body mass index (BMI) decreased from 44.5 +/- 6.31 kg/m(2) (range: 35.0-63.23) to 31.83 +/- 5.83 kg/m(2) (range: 20.9-49.6). The average length of follow-up was 11.3 +/- 5.2 months (range: 5-25). The incidence of urinary symptoms improved after surgery (P=0.003), as did the UDI-6 score (Urogenital distress inventory) (P=0.009). There was no improvement in other symptoms such as prolapse and colorectal-anal dysfunction. CONCLUSION: The prevalence of pelvic floor disorders is high among obese women; in this study, colorectal disorders were present in 53% and urinary disorders in 71.5%. Bariatric surgery-induced weight loss led to improvement in urinary continence disorders when assessed over an average follow-up of 11 months. PMID- 26678849 TI - Proportional Topology Optimization: A New Non-Sensitivity Method for Solving Stress Constrained and Minimum Compliance Problems and Its Implementation in MATLAB. AB - A new topology optimization method called the Proportional Topology Optimization (PTO) is presented. As a non-sensitivity method, PTO is simple to understand, easy to implement, and is also efficient and accurate at the same time. It is implemented into two MATLAB programs to solve the stress constrained and minimum compliance problems. Descriptions of the algorithm and computer programs are provided in detail. The method is applied to solve three numerical examples for both types of problems. The method shows comparable efficiency and accuracy with an existing optimality criteria method which computes sensitivities. Also, the PTO stress constrained algorithm and minimum compliance algorithm are compared by feeding output from one algorithm to the other in an alternative manner, where the former yields lower maximum stress and volume fraction but higher compliance compared to the latter. Advantages and disadvantages of the proposed method and future works are discussed. The computer programs are self-contained and publicly shared in the website www.ptomethod.org. PMID- 26678850 TI - Visual-based quadrotor control by means of fuzzy cognitive maps. AB - By applying an image-based visual servoing (IBVS) method, the intelligent image based controlling of a quadrotor type unmanned aerial vehicle (UAV) tracking a moving target is studied in this paper. A fuzzy cognitive map (FCM) is a soft computing method which is classified as a fuzzy neural system and exploits the main aspects of fuzzy logic and neural network systems; so it seems to be a suitable choice for implementing a vision-based intelligent technique. An FCM has been employed in implementing an IBVS scheme on a quadrotor UAV, so that the UAV can track a moving target on the ground. For this purpose, by properly combining the perspective image moments, some features with the desired characteristics for controlling the translational and yaw motions of a UAV have been presented. In designing a vision-based control method for a UAV quadrotor, there are some challenges, including the target mobility and not knowing the height of UAV above the target. Also, no sensor has been installed on the moving object and the changes of its yaw angle are not available. Despite all the stated challenges, the proposed method, which uses an FCM in controlling the translational motion and the yaw rotation of a UAV, adequately enables the quadrotor to follow the moving target. The simulation results for different paths show the satisfactory performance of the designed controller. PMID- 26678852 TI - ViralEpi v1.0: a high-throughput spectrum of viral epigenomic methylation profiles from diverse diseases. AB - AIMS: To develop a computational resource for viral epigenomic methylation profiles from diverse diseases. MATERIALS & METHODS: Methylation patterns of Epstein-Barr virus and hepatitis B virus genomic regions are provided as web platform developed using open source Linux-Apache-MySQL-PHP (LAMP) bundle: programming and scripting languages, that is, HTML, JavaScript and PERL. RESULTS: A comprehensive and integrated web resource ViralEpi v1.0 is developed providing well-organized compendium of methylation events and statistical analysis associated with several diseases. Additionally, it also facilitates 'Viral EpiGenome Browser' for user-affable browsing experience using JavaScript-based JBrowse. CONCLUSION: This web resource would be helpful for research community engaged in studying epigenetic biomarkers for appropriate prognosis and diagnosis of diseases and its various stages. PMID- 26678853 TI - Plasmafiltration as a possible contributor to kinetic targeting of pegylated liposomal doxorubicin (PLD) in order to prevent organ toxicity and immunosuppression. AB - PURPOSE: To examine the removal of pegylated liposomal doxorubicin (PLD) during plasmafiltration (PF) and determine whether the drug could be withheld prior to its organ distribution responsible for mucocutaneous toxicity. METHODS: Six patients suffering from platinum-resistant ovarian cancer were treated with a 1-h IV infusion 50 mg/m(2) of PLD/cycle-for three cycles q4w. Over 44 (46)-47(49) h postinfusion, five patients (14 cycles in total) underwent PF using a cascade PF method consisted of plasma separation by centrifugation and plasma treatment using filtration based one volume of plasma treatment, i.e., 3.18 L (+/-0.6 L) and plasma flow 1.0 L/h (0.91-1.48 L/h). Doxorubicin concentration in blood was monitored by a high-performance liquid chromatography method for 116 h postinfusion. Pharmacokinetic parameters determined from plasma concentration included volume of distribution, total body clearance, half-life of elimination, and area under the plasma concentration versus time. The amount of doxorubicin in the body eliminated by the patient and via extracorporeal treatment was evaluated. Toxicity was tested using CTCAE v4.0. RESULTS: The efficacy of PF and early responses to PLD/PF combination strategy were as follows: over 44(46) h postinfusion considered necessary for target distribution of PLD to tumor, patients eliminated 46 % (35-56 %) of the dose administered. Over 44(46)-47(49) h postinfusion, a single one-volume plasma filtration removed 40 % (22-45 %) (Mi5) of the remaining doxorubicin amount in the body. Total fraction eliminated attained 81 % (75-86 %). The most common treatment-related adverse events (grade 1-2) such as nausea (4/14 cycles-28 %) and vomiting (3/14 cycles-21 %) appeared during 44 h postinfusion. Hematological toxicity-anemia (5/14 cycles-35 %) was reported after cycle II termination. Symptoms of PPE-like syndrome (grade 1-2) appeared in one patient concomitantly with thrombophlebitis and malignant effusion. In this study, only one adverse reaction (1/14-7 %) as short-term malaise and nausea was reported by the investigator as probably related to PF. CONCLUSION: A single one-volume PF does remove a clinically important amount of doxorubicin in a kinetic targeting approach. There were no serious signs of drug toxicity and/or PF-related adverse events. Kinetically guided therapy with pegylated liposomal doxorubicin combined with PF may be a useful tool to the higher efficacy and tolerability of therapy with PLD. PMID- 26678851 TI - A Hominin Femur with Archaic Affinities from the Late Pleistocene of Southwest China. AB - The number of Late Pleistocene hominin species and the timing of their extinction are issues receiving renewed attention following genomic evidence for interbreeding between the ancestors of some living humans and archaic taxa. Yet, major gaps in the fossil record and uncertainties surrounding the age of key fossils have meant that these questions remain poorly understood. Here we describe and compare a highly unusual femur from Late Pleistocene sediments at Maludong (Yunnan), Southwest China, recovered along with cranial remains that exhibit a mixture of anatomically modern human and archaic traits. Our studies show that the Maludong femur has affinities to archaic hominins, especially Lower Pleistocene femora. However, the scarcity of later Middle and Late Pleistocene archaic remains in East Asia makes an assessment of systematically relevant character states difficult, warranting caution in assigning the specimen to a species at this time. The Maludong fossil probably samples an archaic population that survived until around 14,000 years ago in the biogeographically complex region of Southwest China. PMID- 26678854 TI - Adherence with renal dosing recommendations in outpatients undergoing haemodialysis. AB - WHAT IS KNOWN AND OBJECTIVE: Adjustment of drug dosage in patients with end-stage renal disease prevents serious adverse effects, which occur due to the accumulation of drugs or other toxic metabolites. Nevertheless, dosing errors occur most commonly among patients with end-stage renal disease. The aim of this study was to assess the quality of care for end-stage renal disease outpatients using their renal dosing adjustment status. METHODS: A cross-sectional study was performed using the data collected from 43 South Korean medical institutions via questionnaires. A total of 2428 patients on haemodialysis, who were at least 18 years of age, were included. Among these patients, the study population was confined to patients who were taking medications and required renal dosing adjustments from three therapeutic classes: antihypertensives, antihyperglycaemics and lipid-modifying agents. The study population (n = 828) was prescribed a total of 1097 drug orders for the target drugs. Determination of appropriate dosage adjustment was based on GFR (glomerular filtration rate) using the Modification of Diet in Renal Disease revised 4-variable equation. The primary outcome was non-adherence to drug dosing requirements for end-stage renal disease patients with consideration to their renal function. RESULTS AND DISCUSSION: Among the study population (n = 828), 469 haemodialysis patients were identified as having drug orders that were adherent to renal dosing recommendations. There were significant differences between the patient groups who received recommendation-adherent and non-adherent drug orders in the characteristics of the medical institutions they visited, causes of chronic renal failure and prevalence of concurrent diabetes mellitus. The primary factor of non adherence to renal dosing adjustment recommendations was characteristics of medical institutions. Compared to tertiary hospitals, secondary hospitals and primary care clinics were 1.16 and 1.22 times, respectively, more non-adherent in accordance with the multivariate analysis (OR: 1.16, 95% CI: 1.02-1.20, OR: 1.22, 95% CI: 1.00-1.36, respectively). WHAT IS NEW AND CONCLUSIONS: Dosing error is one of the most common problems among patients with renal failure. To decrease the dosing errors, an improvement needs to be made in medical institutions. This can be accomplished by implementing the clinical decision support systems that educate physicians on appropriate renal dosing and help them prescribe appropriate drug dosages. PMID- 26678855 TI - Where we are now and how we can improve: a qualitative study of practitioners' perspectives on providing ART adherence support in Romania. AB - Supporting medication adherence is a priority in HIV care worldwide as low adherence threatens the effectiveness of antiretroviral treatment (ART). While evidence on adherence causes and consequences has steadily accumulated, investigating current practice and relevant determinants of practitioners' behaviors has only recently been highlighted as essential for developing effective and sustainable interventions. In Romania, ART adherence is low despite universal access to HIV care, and improving support services is a priority. We report a qualitative exploration of practitioners' experiences and views on ART adherence support, guided by current behavioral theory. Semi-structured interviews were performed with 10 practitioners from six HIV centers, aiming for maximum variation sampling on professional experience, location, and organization type. Questions addressed practitioners' views and experiences on assessing patients' adherence behaviors and determinants, content and format of adherence support, and perceived influences on their capacity to deliver support. Verbatim transcripts were analyzed via template analysis. Results show that adherence support is provided in Romania by trained psychologists in multidisciplinary teams that operate flexibly and perform multiple HIV care activities. Assessment of adherence behaviors and determinants is primarily interview-based, and practitioners use mostly psychotherapeutic techniques and theories with a degree of intervention tailoring. Practitioners' descriptions covered a broad range of common determinants and behavior change techniques, but showed limited use of behavioral theory. Participants also described difficulties to cope with limited resources, and lack of support for managing practical and emotional challenges. Several opportunities for improvement were identified, such as standardizing patient profiling and intervention delivery, conceptualizing and recording active intervention content based on behavioral theory, and actively monitoring intervention effectiveness. This qualitative inquiry provided valuable information for improving adherence support in this clinical context. Understanding practitioners' perspectives based on behavioral theory-informed analyses can help intervention developers increase intervention fidelity by integrating current practice information in program design. PMID- 26678856 TI - gamma-Secretase Modulators and APH1 Isoforms Modulate gamma-Secretase Cleavage but Not Position of epsilon-Cleavage of the Amyloid Precursor Protein (APP). AB - The relative increase in Abeta42 peptides from familial Alzheimer disease (FAD) linked APP and PSEN mutations can be related to changes in both epsilon-cleavage site utilization and subsequent step-wise cleavage. Cleavage at the epsilon-site releases the amyloid precursor protein (APP) intracellular domain (AICD), and perturbations in the position of epsilon-cleavage are closely associated with changes in the profile of amyloid beta-protein (Abeta) species that are produced and secreted. The mechanisms by which gamma-secretase modulators (GSMs) or FAD mutations affect the various gamma-secretase cleavages to alter the generation of Abeta peptides have not been fully elucidated. Recent studies suggested that GSMs do not modulate epsilon-cleavage of APP, but the data were derived principally from recombinant truncated epitope tagged APP substrate. Here, using full length APP from transfected cells, we investigated whether GSMs modify the epsilon cleavage of APP under more native conditions. Our results confirmed the previous findings that epsilon-cleavage is insensitive to GSMs. In addition, fenofibrate, an inverse GSM (iGSM), did not alter the position or kinetics of epsilon-cleavage position in vitro. APH1A and APH1B, a subunit of the gamma-secretase complex, also modulated Abeta42/Abeta40 ratio without any alterations in epsilon-cleavage, a result in contrast to what has been observed with PS1 and APP FAD mutations. Consequently, GSMs and APH1 appear to modulate gamma-secretase activity and Abeta42 generation by altering processivity but not epsilon-cleavage site utilization. PMID- 26678857 TI - Stable carbon and nitrogen isotopes as a potential tool to differentiate pork from organic and conventional systems. AB - BACKGROUND: Isotopic discrimination, dietary composition and feeding regime determine the carbon and nitrogen stable isotope ratios of animals. Accordingly, measurement of the stable isotope ratios of carbon and nitrogen can be a potential method to identify patterns of pork production. RESULTS: In the current study, we investigated the carbon and nitrogen isotopic ratio in pork from organic and conventional systems. The average carbon and nitrogen isotope ratios for various organic tissues, including hair, blood and defatted meat, were higher than those of conventionally raised ones. The discriminant analysis results based on the combination of carbon and nitrogen isotopic ratios in defatted meat reached a 100% correct classification. Furthermore, the variation in carbon and nitrogen stable isotope ratios of retail organic and conventional pork has been studied over 1 year. The results suggested that organic pork had a higher delta(13) C value than that of the conventional pork in all but three fortnights. Grouping of the delta(15) N data showed that the delta(15) N value in organic pork was higher than that of the conventional one throughout the whole year. CONCLUSION: The method established in the present study provides a potential detection that can be highly valuable to prevent fraudulent labelling of organic pork. (c) 2015 Society of Chemical Industry. PMID- 26678858 TI - State of the art in biobehavioral approaches to the management of chronic pain in childhood. AB - Chronic pain in childhood is prevalent, persistent and significantly impactful on most domains of life. The chronic pain experience occurs within a complex biopsychosocial framework, with particular emphasis on the social context. Currently, psychological treatments involve a cognitive-behavioral therapy treatment plan, providing some combination of psychoeducation, self-regulation training, maladaptive cognition identification, behavioral exposure and parent involvement. New treatment areas are emerging, such as group- and internet-based cognitive-behavioral therapy, motivational interviewing, comorbid obesity intervention and intensive multidisciplinary rehabilitation. Preliminary studies of emerging treatments demonstrate encouraging results; however, treatment effectiveness hinges on accurate matching of patient to treatment modality. Overall, the current direction of the field promises many innovative breakthroughs to ameliorate suffering in youth with chronic pain. PMID- 26678859 TI - Unique coexistence of cold and solar urticaria and its efficient treatment. PMID- 26678860 TI - Development of a clinically relevant endoscopic grading system for chronic rhinosinusitis using canonical correlation analysis. AB - BACKGROUND: Diagnostic nasal endoscopy is a routine measure of sinonasal inflammation in patients with chronic rhinosinusitis (CRS). Although multiple staging systems have been proposed and evaluated, evidence of association between concurrent symptoms and endoscopic findings remains discordant. The goal of this study is to identify the relevant endoscopic attributes associated with symptom burden, and to systematically derive a weighted endoscopic scale that optimizes prediction of concurrent symptoms. METHODS: Reported baseline symptom (22-item Sino-Nasal Outcome Test [SNOT-22]) and endoscopic evaluation scores (Lund-Kennedy [LK]) were obtained from patients with CRS enrolled in a prospective cohort study. Canonical correlation analysis of the SNOT-22 subdomains and LK variables was completed. RESULTS: A total of 629 patients were included in analysis including 343 with prior endoscopic sinus surgery. Significant canonical correlations outperformed aggregate correlations in explaining variance of the data (33% vs 3%, respectively). The first canonical correlation was dominated by the rhinologic symptom domain and the endoscopic polyp score (r = 0.54; p < 0.05) whereas additional significant canonical correlation was found between the extra rhinologic symptom subdomain and the edema score in patients without prior ESS (r = 0.21; p < 0.05), and discharge in patients with prior ESS (r = 0.22; p < 0.05). All other domains and endoscopic variables did not significantly contribute to the canonical correlation. CONCLUSION: Although aggregate symptoms and endoscopic scores demonstrate minimal correlation, a weighted combination of symptom domains and endoscopic attributes greatly improves this correlation. A simple approximation of the weights of each of the endoscopic variables of polyps, edema, discharge, scarring, and crusting, is an approximate ratio of 4:2:1:0:0, respectively. PMID- 26678861 TI - Optimization of chitosan nanoparticles for colon tumors using experimental design methodology. AB - Purpose Colon-specific drug delivery systems (CDDS) can improve the bio availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer. PMID- 26678862 TI - The variation of PbTiO3 bandgap at ferroelectric phase transition. AB - Optical properties of the PbTiO3 thin films fabricated by chemical solution deposition have been measured with variable angle spectroscopic ellipsometry in the spectral range of 1-6 eV and in the temperature interval from room temperature to 950 K. The optical response functions and band gap energy were determined in the whole temperature range. The direct band gap varies from the value 3.88 eV at room temperature to the value 3.67 eV just above the phase transition. The temperature dependence of the film lattice parameters was also measured by x-ray and it shows a strong correlation with the band gap. The comparison of experimental data with ab initio electronic structure calculations simulating the temperature development of dielectric function and band gap is also presented. PMID- 26678863 TI - Community and clinic-based screening for curable sexually transmissible infections in a high prevalence setting in Australia: a retrospective longitudinal analysis of clinical service data from 2006 to 2009. AB - Background In response to the high prevalence of sexually transmissible infections (STIs) in many central Australian Aboriginal communities, a community wide screening program was implemented to supplement routine primary health care (PHC) clinic testing. The uptake and outcomes of these two approaches were compared. METHODS: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) community and clinic screening data for Aboriginal people aged 15-34 years, 2006 2009, were used. Regression analyses assessed predictors of the first test occurring in the community screen, positivity and repeat testing. RESULTS: A total of 2792 individuals had 9402 tests (median: four per person) over 4 years. Approximately half of the individuals (54%) were tested in the community and clinic approaches combined, 29% (n=806) in the community screen only and 18% (n=490) in the clinic only. Having the first test in a community screen was associated with being male and being aged 15-19 years. There was no difference between community and clinic approaches in CT or NG positivity at first test. More than half (55%) of individuals had a repeat test within 2-15 months and of these, 52% accessed different approaches at each test. The only independent predictor of repeat testing was being 15-19 years. CONCLUSIONS: STI screening is an important PHC activity and the findings highlight the need for further support for clinics to reach young people. The community screen approach was shown to be a useful complementary approach; however, cost and sustainability need to be considered. PMID- 26678864 TI - Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30 month IMAGE-HD data. AB - BACKGROUND: The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant. AIMS: To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance. METHOD: Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months. RESULTS: Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity. CONCLUSIONS: Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials. PMID- 26678867 TI - Welcome to the New Year! PMID- 26678865 TI - Urban-rural differences in incidence rates of psychiatric disorders in Denmark. AB - BACKGROUND: People born in densely populated areas have a higher risk of developing schizophrenia, bipolar disorder and autism. AIMS: The purpose of this study was to investigate whether urban-rural differences in place of birth influence a broad range of mental disorders. METHOD: Population-based cohort study of everyone born in Denmark between 1955 and 2006 (n = 2 894 640). Main outcome measures were incidence rate ratios for five levels of urbanisation and summary estimates contrasting birth in the capital with birth in rural areas. RESULTS: For all psychiatric disorders, except intellectual disability (ICD-10 'mental retardation') and behavioural and emotional disorders with onset in childhood, people born in the capital had a higher incidence than people born in rural areas. CONCLUSIONS: Birth in an urban environment is associated with an increased risk for mental illness in general and for a broad range of specific psychiatric disorders. Given this new evidence that urban-rural differences in incidence are not confined to the well-studied psychotic disorders, further work is needed to identify the underlying aetiopathogenic mechanisms. PMID- 26678866 TI - Evaluation of benefit to patients of training mental health professionals in suicide guidelines: cluster randomised trial. AB - BACKGROUND: Randomised studies examining the effect on patients of training professionals in adherence to suicide guidelines are scarce. AIMS: To assess whether patients benefited from the training of professionals in adherence to suicide guidelines. METHOD: In total 45 psychiatric departments were randomised (Dutch trial register: NTR3092). In the intervention condition, all staff in the departments were trained with an e-learning supported train-the-trainer programme. After the intervention, patients were assessed at admission and at 3 month follow-up. Primary outcome was change in suicide ideation, assessed with the Beck Scale for Suicide Ideation. RESULTS: For the total group of 566 patients with a positive score on the Beck Scale for Suicide Ideation at baseline, intention-to-treat analysis showed no effects of the intervention on patient outcomes at 3-month follow-up. Patients who were suicidal with a DSM-IV diagnosis of depression (n = 154) showed a significant decrease in suicide ideation when treated in the intervention group. Patients in the intervention group more often reported that suicidality was discussed during treatment. CONCLUSIONS: Overall, no effect of our intervention on patients was found. However, we did find a beneficial effect of the training of professionals on patients with depression. PMID- 26678869 TI - Preparation of Three-Dimensional Graphene Foams Using Powder Metallurgy Templates. AB - A simple and scalable method which combines traditional powder metallurgy and chemical vapor deposition is developed for the synthesis of mesoporous free standing 3D graphene foams. The powder metallurgy templates for 3D graphene foams (PMT-GFs) consist of particle-like carbon shells which are connected by multilayered graphene that shows high specific surface area (1080 m(2) g(-1)), good crystallization, good electrical conductivity (13.8 S cm(-1)), and a mechanically robust structure. The PMT-GFs did not break under direct flushing with DI water, and they were able to recover after being compressed. These properties indicate promising applications of PMT-GFs for fields requiring 3D carbon frameworks such as in energy-based electrodes and mechanical dampening. PMID- 26678870 TI - Correction: Lung Transcriptomics during Protective Ventilatory Support in Sepsis Induced Acute Lung Injury. PMID- 26678871 TI - Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation. AB - Several lines of evidence suggest that the amygdala and the bed nucleus of the stria terminalis (BNST) are differentially involved in phasic and sustained fear. Even though, results from neuroimaging studies support this distinction, a specific effect of a temporal dissociation with phasic responses to onset versus sustained responses during prolonged states of threat anticipation has not been shown yet. To explore this issue, we investigated brain activation during anticipation of threat in 38 healthy participants by means of functional magnetic resonance imaging. Participants were presented different visual cues indicated the temporally unpredictable occurrence of a subsequent aversive or neutral stimulus. During the onset of aversive versus neutral anticipatory cues, results showed a differential phasic activation of amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (PFC). In contrast, activation in the BNST and other brain regions, including insula, dorsolateral PFC, ACC, cuneus, posterior cingulate cortex, and periaqueductal grey was characterized by a sustained response during the threat versus neutral anticipation period. Analyses of functional connectivity showed phasic amygdala response as positively associated with activation, mainly in sensory cortex areas whereas sustained BNST activation was negatively associated with activation in visual cortex and positively correlated with activation in the insula and thalamus. These findings suggest that the amygdala is responsive to the onset of cues signaling the unpredictable occurrence of a potential threat while the BNST in concert with other areas is involved in sustained anxiety. Furthermore, the amygdala and BNST are characterized by distinctive connectivity patterns during threat anticipation. PMID- 26678872 TI - [Formula: see text]Children's sense of reality: The development of orbitofrontal reality filtering. AB - Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. In adults, it is mediated by the orbitofrontal cortex and subcortical connections and its failure induces reality confusion, confabulations, and disorientation. Here we investigated for the first time the development of this mechanism in 83 children from ages 7 to 11 years and 20 adults. We used an adapted version of a continuous recognition task composed of two runs with the same picture set but arranged in different order. The first run measures storage and recognition capacity (item memory), the second run measures reality filtering. We found that accuracy and reaction times in response to all stimulus types of the task improved in parallel across ages. Importantly, at no age was there a notable performance drop in the second run. This means that reality filtering was already efficacious at age 7 and then steadily improved as item memory became stronger. At the age of 11 years, reality filtering dissociated from item memory, similar to the pattern observed in adults. However, performance in 11-year-olds was still inferior as compared to adults. The study shows that reality filtering develops early in childhood and becomes more efficacious as memory capacity increases. For the time being, it remains unresolved, however, whether this function already depends on the orbitofrontal cortex, as it does in adults, or on different brain structures in the developing brains of children. PMID- 26678873 TI - Exploring the association of dairy product intake with the fatty acids C15:0 and C17:0 measured from dried blood spots in a multipopulation cohort: Findings from the Food4Me study. AB - SCOPE: The use of biomarkers in the objective assessment of dietary intake is a high priority in nutrition research. The aim of this study was to examine pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) as biomarkers of dairy foods intake. METHODS AND RESULTS: The data used in the present study were obtained as part of the Food4me Study. Estimates of C15:0 and C17:0 from dried blood spots and intakes of dairy from a Food Frequency Questionnaire were obtained from participants (n = 1180) across seven countries. Regression analyses were used to explore associations of biomarkers with dairy intake levels and receiver operating characteristic analyses were used to evaluate the fatty acids. Significant positive associations were found between C15:0 and total intakes of high-fat dairy products. C15:0 showed good ability to distinguish between low and high consumers of high-fat dairy products. CONCLUSION: C15:0 can be used as a biomarker of high-fat dairy intake and of specific high-fat dairy products. Both C15:0 and C17:0 performed poorly for total dairy intake highlighting the need for caution when using these in epidemiological studies. PMID- 26678874 TI - Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. AB - Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus. PMID- 26678875 TI - Architecture of human mTOR complex 1. AB - Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino terminal domain of Raptor is juxtaposed to the kinase active site. PMID- 26678876 TI - Lunar atmosphere. How surface composition and meteoroid impacts mediate sodium and potassium in the lunar exosphere. AB - Despite being trace constituents of the lunar exosphere, sodium and potassium are the most readily observed species due to their bright line emission. Measurements of these species by the Ultraviolet and Visible Spectrometer (UVS) on the Lunar Atmosphere and Dust Environment Explorer (LADEE) have revealed unambiguous temporal and spatial variations indicative of a strong role for meteoroid bombardment and surface composition in determining the composition and local time dependence of the Moon's exosphere. Observations show distinct lunar day (monthly) cycles for both species as well as an annual cycle for sodium. The first continuous measurements for potassium show a more repeatable variation across lunations and an enhancement over KREEP (Potassium Rare Earth Elements and Phosphorus) surface regions, revealing a strong dependence on surface composition. PMID- 26678877 TI - The evolution of antievolution policies after Kitzmiller versus Dover. PMID- 26678878 TI - An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic MERS-CoV introductions from dromedary camels. In addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of MERS-CoV spread from the animal reservoir may be envisaged. Here we show that a modified vaccinia virus Ankara (MVA) vaccine expressing the MERS-CoV spike protein confers mucosal immunity in dromedary camels. Compared with results for control animals, we observed a significant reduction of excreted infectious virus and viral RNA transcripts in vaccinated animals upon MERS-CoV challenge. Protection correlated with the presence of serum neutralizing antibodies to MERS-CoV. Induction of MVA-specific antibodies that cross-neutralize camelpox virus would also provide protection against camelpox. PMID- 26678879 TI - High-flow support in very preterm infants in Australia and New Zealand. AB - BACKGROUND: Randomised trials suggest that high-flow (HF) therapy is comparable with continuous positive airway pressure (CPAP) for postextubation respiratory support in neonates, and HF has been widely adopted in neonatal intensive care. METHODS: We conducted a population-based study of very preterm infants born <32 weeks' gestation within the Australian and New Zealand Neonatal Network (ANZNN) data set from 2009 to 2012, who received respiratory support with HF. RESULTS: 3372 very preterm infants were treated with HF. HF use in this population increased significantly from 15% in 2009 to 35% in 2012. In 2012, 53% (542/1029) of extremely preterm infants born <28 weeks' gestation received HF. 98% (3308/3372) of infants had received endotracheal ventilation or CPAP prior to receiving HF. The maximum HF gas flow was <=8 L/min in almost all infants. CONCLUSIONS: HF use in extremely preterm and very preterm infants increased significantly within the ANZNN from 2009 to 2012. PMID- 26678881 TI - Self-treatment of foot ulcers as a risk factor for delayed diagnosis of acral melanoma. PMID- 26678880 TI - Importance of immunopharmacogenomics in cancer treatment: Patient selection and monitoring for immune checkpoint antibodies. AB - In the last 5 years, immune checkpoint antibodies have become established as anticancer agents for various types of cancer. These antibody drugs, namely cytotoxic T-lymphocyte-associated antigen, programmed death-1, and programmed death ligand-1 antibodies, have revealed relatively high response rates, the ability to induce durable responses, and clinical efficacy in malignancies not previously thought to be susceptible to immune-based strategies. However, because of its unique mechanisms of activating the host immune system against cancer as well as expensive cost, immune checkpoint blockade faces novel challenges in selecting appropriate patient populations, monitoring clinical responses, and predicting immune adverse events. The development of objective criteria for selecting patient populations that are likely to have benefit from these therapies has been vigorously investigated but still remains unclear. In this review, we describe immune checkpoint inhibition-specific challenges with patient selection and monitoring, and focus on approaches to remedy these challenges. We also discuss applications of the emerging field of immunopharmacogenomics for guiding selection and monitoring for anti-immune checkpoint treatment. PMID- 26678883 TI - The complete maternal mitochondrial genome of rare Chinese freshwater mussel Lepidodesma languilati (Bivalvia: Unionidae: Unioninae). AB - Lepidodesma languilati is considered threatened because of the influence of human activities in China. The complete F-type mitochondrial genome of L. languilati was determined in this study (GenBank accession no. KT381195). It is a 15 754-bp long circular molecule that consists of 37 genes that are typically found in other invertebrates. The overall base composition of the entire sequence is as follows: A (39.1%), T (25.7%), C (23.4%), and G (11.8%). Except for cox1 (TTG), cob (ATT), nad1 (ATT), nad6 (ATA), nad4 (TTG), and atp8 (GTG), 7 of the 13 protein-coding genes initiate with orthodox ATG start codon. All the 13 protein coding genes have complete termination codon TAA or TAG. Phylogenetic tree indicates that L. languilati belongs to Unioninae. The newly sequenced complete mitogenome can provide basic data for comparative studies on mitochondrial genomes of Unionidae. It could also lay the important theoretical foundation for phylogenetics, population genetics, germplasm resources protection, sustainable, and reasonable utilization. PMID- 26678882 TI - Towards rationalisation of antivenom use in funnel-web spider envenoming: enzyme immunoassays for venom concentrations. AB - CONTEXT: Funnel-web spider (Atrax and Hadronyche spp.) envenoming is rare but causes severe neuromuscular, autonomic, and cardiac effects. A rabbit-derived IgG antivenom is available, but venom detection in patients has not been reported. OBJECTIVE: To use serial venom and antivenom concentrations to better define envenoming and antivenom effectiveness. MATERIALS AND METHODS: Serum was collected from nine patients with suspected funnel-web spider bites and clinical effects were recorded. Venom-specific enzyme immunoassays were developed to measure funnel-web spider venom and antivenom concentrations. Goat anti-rabbit whole serum was coupled to UltraLink resin and added to samples to remove bound venom and measure free venom. Antivenom efficacy was defined as antivenom binding all free venom and antivenom effectiveness as resolution of clinical features. RESULTS: Venom was detectable in samples from six of nine patients. In three patients without venom detected, there were only moderate effects, which did not completely respond to antivenom in all cases and no spider was identified. In five of six cases, a male Atrax spp. (Sydney funnel-web) spider was identified. Three patients had moderate envenoming which responded to antivenom. Three patients had severe envenoming and developed catecholamine-induced myocarditis and acute pulmonary oedema. Although cholinergic and non-specific clinical features appeared to respond to antivenom, myocarditis and pulmonary oedema lasted 2-4 days. Median venom concentration pre-antivenom in five patients with samples was 5.6 ng/ml (3-35 ng/ml), and immediately post-antivenom decreased to a median of 0 ng/ml (0-1.8 ng/ml). Post-antivenom venom concentrations decreased when bound venom was removed; median, 0 ng/ml (0-0.9 ng/ml), indicating that most venom detected post-antivenom was bound. There was recurrence of venom and clinical features in one patient when a pressure bandage was removed. CONCLUSIONS: Detection of venom in suspected funnel-web spider bites identified definite cases with characteristic envenoming and a spider was identified. Measurement of venom concentrations pre- and post-antivenom demonstrated that venom was bound by antivenom, but in severe cases cardiac toxicity was not reversed. PMID- 26678884 TI - Downregulation of SATB1 increases the invasiveness of Jurkat cell via activation of the WNT/beta-catenin signaling pathway in vitro. AB - Special AT-rich sequence-binding protein-1 (SATB1) is critical for genome organizer that reprograms chromatin organization and transcription profiles, and associated with tumor growth and metastasis in several cancer types. Many studies suggest that SATB1 overexpression is an indicator of poor prognosis in various cancers, such as breast cancer, malignant cutaneous melanoma, and liver cancer. However, their expression patterns and function values for adult T cell leukemia (ATL) are still largely unknown. The aim of this study is to examine the levels of SATB1 in ATL and to explore its function and mechanisms in Jurkat cell line. Here, we reported that SATB1 expressions were decreased in ATL cells (p < 0.001) compared with normal controls. Knockdown of SATB1 expression significantly enhanced invasion of Jurkat cell in vitro. Furthermore, knockdown of SATB1 gene enhances beta-catenin nuclear accumulation and transcriptional activity and thus may increase the invasiveness of Jurkat cell through the activation of Wnt/beta catenin signaling pathway in vitro. PMID- 26678885 TI - Prognostic value of ABO blood group in patients with early stage cervical cancer treated with radical hysterectomy with pelvic node dissection. AB - This study aimed to evaluate the prognostic value of ABO blood groups in early stage cervical cancer patients. The cohort included 413 patients diagnosed with stages IA2-IB1 cervical cancer who received a radical hysterectomy between 2002 and 2014. The 5-year recurrence-free survival (RFS) and overall survival (OS) were 93.13 and 96.81 % for blood group O, 87.68 and 88.22 % for blood group A, 81.66 and 89.40 % for blood group B, and 83.12 and 94.12 % for blood group AB groups, respectively. Patients were stratified for analysis as either blood group O or non-O. The 5-year RFS and OS were 93.13 and 96.81 % for blood group O and 83.66 and 89.76 % for blood group non-O, respectively. In multivariate analysis, age (P = 0.025), histology (P = 0.020), and deep stromal invasion (P = 0.006) were independent adverse prognostic factors for RFS, while the statistically significant independent prognostic factors for OS were age (P = 0.007) and parametrial involvement (P < 0.001). The Cox model did not show any significant effects of non-O blood group on survival outcome. However, a time-varying-effect Cox model revealed that the non-O blood group was associated with a worse RFS (hazard ratio (HR) 2.69, 95 % confidence interval (95%CI) 1.12-6.46, P = 0.017) and OS (HR 3.13, 95%CI 0.88-11.16, P = 0.053) during the first 5 years. These findings suggest that early-stage cervical cancer patients with a non-O blood group have poorer RFS than the O blood group, which is evidence during the first 5 years. PMID- 26678886 TI - The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression. AB - Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease. PMID- 26678887 TI - CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer. AB - The CXCL12-CXCR4 axis is proposed to mediate metastasis formation. In this study, we examined CXCL12, CXCR4 and the relative CXCL12-CXCR4 expression as prognostic factors in two cohorts of colon cancer patients. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to study CXCR4, CXCL12 and relative CXCL12 CXCR4 expression in tissue microarrays. Our study included totally 596 patients, 290 in cohort 1 and 306 in cohort 2. For tumour, node, metastasis (TNM) stage III, low nuclear expression of CXCR4 was a positive prognostic factor for 5-year disease-free survival (DFS) in cohort 1 (P = 0.007) and cohort 2 (P = 0.023). In multivariate analysis for stage III, nuclear expression of CXCR4 in cohort 1 was confirmed as a prognostic factor for DFS (hazard ratio (HR), 0.27; 95 % CI, 0.09 to 0.77). For TNM stage III, high cytoplasmic expression of CXCL12 was associated with better 5-year DFS in both cohorts (P = 0.006 and P = 0.006, respectively). We further validated the positive prognostic value of CXCL12 expression for 5 year DFS in stage III with ISH (P = 0.022). For TNM stage III, the relative CXCL12-CXCR4 expression (CXCL12 > CXCR4 vs CXCL12 = CXCR4 vs CXCL12 < CXCR4) was a prognostic factor for 5-year DFS in cohort 1 (92 % vs 46 % vs 31 %, respectively; P < 0.001) and cohort 2 (92 % vs 66 % vs 30 %, respectively; P = 0.006). In conclusion, CXCL12 and relative CXCL12-CXCR4 expression are independent prognostic factors for 5-year DFS in TNM stage III colon cancer. PMID- 26678888 TI - Preoperative ultrasonography and serum thyroid-stimulating hormone on predicting central lymph node metastasis in thyroid nodules as or suspicious for papillary thyroid microcarcinoma. AB - The purpose of this study was to describe the ultrasonography (US) image features and preoperative thyroid-stimulating hormone (TSH) level in patients with thyroid nodules read as or suspicious for papillary thyroid microcarcinoma (PTMC) on US guided fine-needle aspiration biopsy (US-FNAB) and to identify the risk factors for central lymph node metastasis (CLNM) that can guide surgical strategies for patients diagnosed with PTMC on pathology. In this retrospective cross-sectional study, a total of 163 patients diagnosed cytologically and histopathologically were included. Cytological diagnosis for each patient preoperatively was based on the Bethesda classification for the nodule: 44 (27.0 %) were suspicious for papillary carcinoma (Bethesda V) and 119 (73.0 %) were positive for papillary carcinoma (Bethesda VI). PTMC was confirmed in 162 patients on pathology. In the multivariate analysis, the US suspicious images including nodal metastases, microcalcification, and irregular margins, tumor size larger than 7 mm on US, and serum TSH level equal to or greater than 2.5 mIU/L were independent predictors for CLNM in 162 patients diagnosed with PTMC. Prophylactic central lymph node dissection (CLND) may be considered in PTMC patients presenting with risk factors. PMID- 26678889 TI - MicroRNA-9 promotes proliferation of leukemia cells in adult CD34-positive acute myeloid leukemia with normal karyotype by downregulation of Hes1. AB - Acute myeloid leukemia (AML) is a group of heterogeneous hematopoietic malignancies sustained by leukemic stem cells (LSCs) that can resist treatment. Previously, we found that low expression of Hes1 was a poor prognostic factor for AML. However, the activation status of Hes1 and its regulation in LSCs and leukemic progenitors (LPs) as well as normal hematopoietic stem cells (HSCs) in Hes1-low AML patients have not been elucidated. In this study, the expression of Hes1 in LSCs and LPs was analyzed in adult CD34(+) Hes1-low AML with normal karyotype and the upstream microRNA (miRNA) regulators were screened. Our results showed that the level of either Hes1 or p21 was lower in LSCs or LPs than in HSCs whereas the level of miR-9 was highest in LPs and lowest in HSCs. An inverse correlation was observed in the expression of Hes1 and miR-9. Furthermore, we validated miR-9 as one of the regulators of Hes1 by reporter gene analysis. Knockdown of miR-9 by lentivirus infection suppressed the proliferation of AML cells by the induction of G0 arrest and apoptosis in vitro. Moreover, knockdown of miR-9 resulted in decreased circulating leukemic cell counts in peripheral blood and bone marrow, attenuated splenomegaly, and prolonged survival in a xenotransplant mouse model. Our results indicate that the miR-9 plays an important role in supporting AML cell growth and survival by downregulation of Hes1 and that miR-9 has potential as a therapeutic target for treating AML. PMID- 26678890 TI - Inhibition of CXCR4 and CXCR7 for reduction of cell proliferation and invasion in human endometrial cancer. AB - As one of the most common malignant cancers in female reproductive tract, endometrial cancer accounts for 20-30 % of the most frequent gynecological malignancy, which is originated from endometrial epithelial. The molecular mechanisms for the generation of endometrial cancer are up to now unclear, hindering the development of corresponding therapy. CXCR4 and CXCR7 were receptors of CXCL12 chemokine ligand, which could regulate critical procedures of neoplastic transformation, including proliferation, invasion, and apoptosis of the cells. The messenger RNA (mRNA) and protein expression levels of CXCR4 and CXCR7 in human endometrial adenocarcinoma cancer, as well as in Ishikawa and HEC 1-A cell line, were analyzed by using reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. In order to explore the biological function of CXCR4 and CXCR7 in endometrial tumor, small interference RNAs of CXCR4 and CXCR7 fragments were designed, synthesized, and transfected into Ishikawa and HEC-1-A by using Lipofectamine2000. The influence of RNA interference (RNAi)-mediated silencing CXCR4 and CXCR7 on the cell proliferation was investigated under CCK-8. The invasion assay was performed transwell, and cell apoptosis was tested by FCM. Higher mRNA and protein expression levels of CXCR4 and CXCR7 were investigated in endometrial adenocarcinomas. The expression levels of CXCR4 and CXCR7 could be inhibited by RNA interference, reducing the cell proliferation, invasion in Ishikawa and HEC-1-A cells. In this study, we also observed that treated with CXCR4 and CXCR7 small interfering RNA (siRNA) arrested cells in S phase. CXCL12/CXCR4 and CXCL12/CXCR7 receptor ligand systems affect the invasion of endometrial carcinoma cell line into Ishikawa and HEC-1-A. CXCR4 and CXCR7 were silenced by RNAi, which can inhibit the invasion of Ishikawa and HEC-1-A cell lines. Hence, CXCR4 and CXCR7 are expected to become two target genes for the treatment of endometrial carcinoma. PMID- 26678891 TI - Tumor-suppressive microRNA-34a inhibits breast cancer cell migration and invasion via targeting oncogenic TPD52. AB - The tumor protein D52 (TPD52) is an oncogene overexpressed in breast cancer. Although the oncogenic effects of TPD52 are well recognized, how its expression and the role in migration/invasion is still not clear. This study tried to explore the regulative role of microRNA-34a (miR-34a), a tumor suppressive miRNA, on TPD52 expression in breast cancer. The expression of miR-34a was found significantly decreased in breast cancer specimens with lymph node metastases and breast cancer cell lines. The clinicopathological characteristics analyzed showed that lower expression levels of miR-34a were associated with advanced clinical stages. Moreover, TPD52 was demonstrated as one of miR-34a direct targets in human breast cancer cells. miR-34a was further found significantly repress epithelial-mesenchymal transition (EMT) and inhibit breast cancer cell migration and invasion via TPD52. These findings indicate that miR-34a inhibits breast cancer progression and metastasis through targeting TPD52. Consequently, our data strongly suggested that oncogenic TPD52 pathway regulated by miR-34a might be useful to reveal new therapeutic targets for breast cancer. PMID- 26678892 TI - The tumor-to-breast volume ratio (TBR) predicts cancer-specific survival in breast cancer patients who underwent modified radical mastectomy. AB - Breast cancer is the most common cancer in women globally, and tumor size measured as the largest diameter of the tumor focus is currently used in tumor lymph node-metastasis (TNM) staging for prognosis and treatment decisions. The present study utilized the tumor-to-breast volume ratio (TBR) to evaluate the relative tumor size and determined the prognostic impact of TBR on survival in patients with breast cancer. Two thousand twenty-five consecutive breast cancer patients who underwent modified radical mastectomy between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled in this retrospective study. Kaplan-Meier analysis was used to assess the prognostic effect of TBR on cancer-specific survival (CSS), and univariate log-rank test and multivariate Cox proportional hazards regression model were performed to identify independent prognostic factors. The optimal cutoff value of TBR was determined to be 1.70 %, and 1473 and 552 patients were categorized to low-TBR and high-TBR groups, respectively. In the whole patient cohort, CSS was significantly shorter in the high-TBR group (110.2 vs 128.5 months, P < 0.001). Univariate and multivariate analyses revealed that TBR was an independent prognostic factor of CSS in breast cancer patients (hazard ratio (HR) 1.489, 95 % CI 1.130-1.961, P = 0.005). High TBR was independently associated with poor prognosis in breast cancer patients. This variable may serve as a valuable parameter to predict the outcomes of breast cancer. PMID- 26678893 TI - Overexpression of interleukins IL-17 and IL-8 with poor prognosis in colorectal cancer induces metastasis. AB - Current evidences indicated that a group of soluble mediators called chemokines is involved in tumor growth and metastasis. The association of IL-8 with tumor cell migration was previously found, and its expression was related to angiogenesis, tumor progression, and metastasis in many kinds of carcinomas in human and animal models. Furthermore, it has been showed that IL-17 plays its role as either a proteome of tumor progression or antitumor indifferent cancer models. To investigate the messenger RNA (mRNA) expressions of IL-8 and IL-17 in patients with colorectal cancer (CRC) and non-tumor tissue, quantitative real time PCR was used in the study. Our results showed that expression of IL-8 mRNA was significantly increased in tumor tissues (mean +/- SD 3.84 +/- 0.08) compared with adjacent normal mucosa (mean +/- SD 1.17 +/- 0.75, P = 0.001). Furthermore, a higher expression of IL-17 mRNA was found in tumor tissues (mean +/- SD 2.73 +/ 0.69) when compared with normal tissues (mean +/- SD 1.06 +/- 0.07, P = 0.001). Our findings indicated that advanced tumor-node-metastasis (TNM) stage (P = 0.024) and histological grade (poorly differentiated, P = 0.013) and distant metastasis (P = 0.001) were correlated with expression of IL-8. Moreover, high expression of IL-17 showed significant association with early stage CRC (TNM) (P = 0.038). In conclusion, the expression of IL-8 and IL-17 mRNAs was significantly increased in tumor tissues compared with adjacent normal tissues. We found that advanced TNM stage and histological grade and distant metastasis were correlated with expression of IL-8, while high expression of IL-17 showed significant association with early stage CRC (TNM) stage and overexpression of IL-8 may be associated with progression of CRC. PMID- 26678894 TI - Programmed death 1 expression in the peritumoral microenvironment is associated with a poorer prognosis in classical Hodgkin lymphoma. AB - Programmed cell death protein-1 (PD-1) inhibitor may be therapeutic in patients with relapsed or refractory classical Hodgkin's lymphoma (cHL). This study examined the prognostic significance of PD-1 and two PD-1 ligands (PD-L1 and PD L2) in uniformly treated cHL. Diagnostic tissues from 109 cHL patients treated with a doxorubicin, bleomycin, vinblastine, and dacarbazine regimen were evaluated retrospectively by immunohistochemical analysis of PD-L1, PD-L2, and PD 1 expressions. The median follow-up time was 4.91 years (range, 0.17-17.33 years). Thirteen patients (11 %) expressed PD-1 protein in the peritumoral microenvironment, which was associated with poor overall survival (OS) (P = 0.017). PD-L1 or PD-L2 expression was not associated with OS. There was no correlation between PD-L1 and PD-1 expression or between PD-L2 and PD-1 expression. Multivariate analysis identified PD-1 protein as an independent prognostic factor for OS (P = 0.019). Subgroup analysis according to the Ann Arbor stage of cHL showed that PD-1 protein expression had a prognostic value in limited-stage cHL (P = 0.048). PD-1 is an independent prognostic factor in cHL and may allow the identification of a subgroup of patients with limited-stage cHL who require more intensive therapy and who may benefit from anti-PD-1 agents. PMID- 26678895 TI - Differences in limb volume trajectories after breast cancer treatment. AB - PURPOSE: Approximately 20 % of patients develop lymphedema (LE) following breast cancer (BC) surgery. An evaluation of distinct trajectories of volume change may improve our ability to diagnose LE sooner. The purposes of this study were to identify subgroups of women with distinct trajectories of limb volume changes following BC surgery and to evaluate for phenotypic differences among these classes. METHODS: In this prospective longitudinal study, 380 women were enrolled prior to unilateral BC surgery. Upper limb bioimpedance was measured preoperatively and serially for 1 year postoperatively. Resistance ratios (RRs) were calculated. A RR of >1 indicates affected limb volume > unaffected limb volume. Latent class growth analysis (LCGA) was used to identify classes of women with distinct postoperative RR trajectories. Differences among classes were evaluated using analyses of variance and chi-square analyses. RESULTS: Three distinct classes were identified as follows: RR <0.95 (37.9 %), RR ~1.00 (46.8 %), and RR >1.05 (15.3 %). Patients in the RR >1.05 class were more likely to have diabetes (p = 0.036), were more likely to have BC on their dominant side (p < 0.001), had higher RR ratios at the preoperative and 1-month assessments (p < 0.001), and were more likely to be diagnosed with LE (p < 0.001). CONCLUSIONS: LCGA is a useful analytic technique to identify subgroups of women who may be at higher risk for the development of LE, based on trajectories of limb volume change after BC surgery. IMPLICATIONS FOR CANCER SURVIVORS: Assessment of preoperative and 1-month bioimpedance RRs may allow for the earlier identification of patients who are at higher risk for the development of LE. PMID- 26678896 TI - [The Ocularpathologist in Everday Clinical Routine]. PMID- 26678897 TI - [Editorial: New Technologies]. PMID- 26678898 TI - [Nonlinear Microscopy in Ophthalmology: Principles and Pathbreaking Applications]. AB - Nonlinear microscopy is a non-invasive imaging technique which allows a visualization of biological tissue with high signal contrast due to spectral separation combined with high resolution. In addition to two-photon fluorescence and second harmonic signals also four-wave mixing signals can be used for imaging ocular structures. This review article presents the physical principles of different contrast mechanisms. Exemplary experimental results based on various nonlinear signals are shown, opportunities of this technology are discussed and the prospect of translating this imaging technique into a clinical application is addressed. PMID- 26678899 TI - [Coupled Analysis of Fluid-Structure Interaction of a Micro-Mechanical Valve for Glaucoma Drainage Devices]. AB - BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. In therapeutically refractory cases, alloplastic glaucoma drainage devices (GDD) are being increasingly used to decrease intraocular pressure. Current devices are mainly limited by fibrotic encapsulation and postoperative hypotension. Preliminary studies have described the development of a glaucoma microstent to control aqueous humour drainage from the anterior chamber into the suprachoroidal space. One focus of these studies was on the design of a micro-mechanical valve placed in the anterior chamber to inhibit postoperative hypotension. The present report describes the coupled analysis of fluid-structure interaction (FSI) as basis for future improvements in the design micro-mechanical valves. MATERIALS AND METHODS: FSI analysis was carried out with ANSYS 14.5 software. Solid and fluid geometry were combined in a model, and the corresponding material properties of silicone (Silastic Rx-50) and water at room temperature were assigned. The meshing of the solid and fluid domains was carried out in accordance with the results of a convergence study with tetrahedron elements. Structural and fluid mechanical boundary conditions completed the model. The FSI analysis takes into account geometric non-linearity and adaptive remeshing to consider changing geometry. RESULTS: A valve opening pressure of 3.26 mmHg was derived from the FSI analysis and correlates well with the results of preliminary experimental fluid mechanical studies. Flow resistance was calculated from non linear pressure-flow characteristics as 8.5 * 10(-3) mmHg/ul . min(-1) and 2.7 * 10(-3) mmHg/ul . min(-1), respectively before and after valve opening pressure is exceeded. FSI analysis indicated leakage flow before valve opening, which is due to the simplified model geometry. CONCLUSIONS: The presented bidirectional coupled FSI analysis is a powerful tool for the development of new designs of micro-mechanical valves for GDD and may help to minimise the time and cost expended on manufacturing and testing prototypes. Further optimisation of the FSI model is expected to ensure further convergence between the simulation and the results of experimental investigations. PMID- 26678900 TI - [Implant Design by Means of Multiphoton Polymerization]. AB - BACKGROUND: Additive manufacturing and 3D printing create new paths for the design and manufacturing of implants. Technologies with high resolution are required for the development of microstructured eye implants. In the present study, we demonstrate how these technologies can be used during the design development and manufacturing of a multifocal diffractive aspheric intraocular lens. MATERIAL AND METHODS: Multiphoton polymerisation (MPP) is used to manufacture a diffractive relief with resolution in the sub-micrometer range. The relief is applied to the moulded body of a refractive lens, forming a trifocal lens. Propagation of light behind the lens is visualised in water with fluorescein. RESULTS: Multifocal lenses were successfully manufactured with this approach. The optical design with three foci is confirmed by the light propagation images. The images even clearly demonstrate the impact of the refractive and diffractive elements and may provide information on artefacts and aberrations. CONCLUSIONS: Multiphoton polymerisation is an interesting tool for the flexible manufacturing of complex multifocal lenses. With future technological progress in 3D printing with MPP, this is a promising method for on demand manufacturing of patient individual intraocular lenses. PMID- 26678901 TI - [Diffusion Weighted Magnetic Resonance Imaging and its Application in Ophthalmology]. AB - The value of diffusion-weighted magnet resonance imaging (DWI-MRI) has been demonstrated for an ever growing range of clinical indications. DWI is sensitive to the diffusion of water molecules and probes their random displacement within tissue. DWI provides both qualitative and quantitative information on tissue characteristics, e.g. tissue cellularity. This review provides an overview of diffusion-weighted imaging and its emerging applications in ophthalmology. The basic physics and technical foundations of DWI are introduced. The emerging applications of DWI are surveyed, particularly in diseases of the eye, orbit and optical nerve. PMID- 26678902 TI - [Cross-Linking in Keratoconus: "Epi-off" or "Epi-on"?]. AB - Corneal cross-linking can halt the progression of keratoconus, but what is the best approach for treatment? There are a number of treatment options for keratoconus, but only corneal cross-linking (CXL) appears to halt the progression of the disease. To guarantee effective cross-linking, CXL treatment involves removal of the corneal epithelium prior to riboflavin application and ultraviolet light illumination - "epi-off" CXL. Several methods of "epi-on" (transepithelial) CXL have been proposed, such as keeping the corneal epithelium intact which should be less painful and help avoid other CXL-associated adverse events. The evidence so far is that epi-off CXL remains the most effective method of strengthening the cornea and slowing keratoconus progression - but transepithelial methods are gaining ground. PMID- 26678903 TI - [Conception and Content Validation of a Questionnaire Relating to the Potential Need for Information of Visually Impaired Persons with Regard to Services and Contact Persons]. AB - A questionnaire was drafted to identify the needs of visually impaired persons and to optimize their access to non-medical support and services. Subjects had to rate a list of 15 everyday activities that are typically affected by visual impairment (for example, being able to orient themselves in the home environment), by indicating the degree to which they perceive each activity to be affected, using a four-stage scale. They had to evaluate these aspects by means of a relevance assessment. The needs profile derived from this is then correlated with individualized information for assistance and support. The questionnaire shall be made available for use by subjects through advisers in some ophthalmic practices and via the internet. The validity of the content of the proposed tool was evaluated on the basis of a survey of 59 experts in the fields of medical, optical and psychological care and of persons involved in training initiatives. The experts were asked to rate the activities by relevance and clarity of the wording and to propose methods to further develop and optimize the content. The validity of the content was quantified according to a process adopted in the literature, based on the parameters Interrater Agreement (IRA) and Content Validity Index (CVI). The results of all responses (n = 19) and the sub-group analysis suggest that the questionnaire adequately reflects the potential needs profile of visually impaired persons. Overall, there was at least 80% agreement among the 19 experts for 93% of the proposed parameterisation of the activities relating to the relevance and clarity of the wording. Individual proposals for optimization of the design of the questionnaire were adopted. PMID- 26678904 TI - [DMEK in a Case of Haab's Striae in Congenital Glaucoma]. PMID- 26678905 TI - [Letter to the Editor on Anterior Chamber Antibiotic Treatment]. PMID- 26678906 TI - [Commentary for Letter to the Editor on Anterior Chamber Antibiotic Treatment]. PMID- 26678907 TI - [Not Available]. PMID- 26678908 TI - Cellular Adaptation to VEGF-Targeted Antiangiogenic Therapy Induces Evasive Resistance by Overproduction of Alternative Endothelial Cell Growth Factors in Renal Cell Carcinoma. AB - Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy significantly inhibits the growth of clear cell renal cell carcinoma (RCC). Eventually, therapy resistance develops in even the most responsive cases, but the mechanisms of resistance remain unclear. Herein, we developed two tumor models derived from an RCC cell line by conditioning the parental cells to two different stresses caused by VEGF-targeted therapy (sunitinib exposure and hypoxia) to investigate the mechanism of resistance to such therapy in RCC. Sunitinib-conditioned Caki-1 cells in vitro did not show resistance to sunitinib compared with parental cells, but when tested in vivo, these cells appeared to be highly resistant to sunitinib treatment. Hypoxia-conditioned Caki-1 cells are more resistant to hypoxia and have increased vascularity due to the upregulation of VEGF production; however, they did not develop sunitinib resistance either in vitro or in vivo. Human endothelial cells were more proliferative and showed increased tube formation in conditioned media from sunitinib-conditioned Caki-1 cells compared with parental cells. Gene expression profiling using RNA microarrays revealed that several genes related to tissue development and remodeling, including the development and migration of endothelial cells, were upregulated in sunitinib-conditioned Caki-1 cells compared with parental and hypoxia-conditioned cells. These findings suggest that evasive resistance to VEGF targeted therapy is acquired by activation of VEGF-independent angiogenesis pathways induced through interactions with VEGF-targeted drugs, but not by hypoxia. These results emphasize that increased inhibition of tumor angiogenesis is required to delay the development of resistance to antiangiogenic therapy and maintain the therapeutic response in RCC. PMID- 26678909 TI - Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome. AB - Non-small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) beta, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERbeta and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER)2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERbeta and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERbeta-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERbeta-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERbeta positive cases and squamous cell carcinoma. PMID- 26678910 TI - Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia. AB - Anoikis, a cell death mechanism triggered upon cell-matrix detachment, is regarded as a physiological suppressor of metastasis that can be regulated by a diverse array of signals. The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) beta superfamily with emerging yet controversial roles in carcinogenesis. In an attempt to identify the function of growth and differentiation factor 2 (GDF2) in epithelial systems, we examined the signaling machinery that is involved and cell fate decisions in response to GDF2 in ovarian and breast epithelia. We find that GDF2 can robustly activate the SMAD1/5 signaling axis by increasing complex formation between the type I receptor serine threonine kinases activin receptor like kinase (ALK) 3 and ALK6 and the type II receptor serine threonine kinase BMPRII. This activation is independent of cross talk with the SMAD2-transforming growth factor beta pathway. By activating SMAD1/5, epithelial cells regulate anchorage-independent growth by increasing anoikis sensitivity that is dependent on GDF2's ability to sustain the activation of SMAD1/5 via ALK3 and ALK6. Consistent with a role for GDF2 in promoting anoikis susceptibility, the analysis of cell lines and patient data suggests epigenetic silencing of GDF2 in cancer cell lines and increased promoter methylation in patients. These findings collectively indicate an antimetastatic role for GDF2 in ovarian and breast cancer. The work also implicates loss of GDF2 via promoter methylation-mediated downregulation in promotion of carcinogenesis with significant relevance for the use of epigenetic drugs currently in clinical trials. PMID- 26678911 TI - CD45RO(+) Memory T Lymphocytes--a Candidate Marker for TNM-Immunoscore in Squamous Non-Small Cell Lung Cancer. AB - Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO(+) memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor tissue samples from two cohorts including in total 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. The density of CD45RO(+) and CD8(+) TILs in tumor epithelial and stromal compartments of the tumors was evaluated by immunohistochemistry. In univariate analyses, intraepithelial CD45RO(+) TIL density (T-CD45RO) was a significant prognostic factor for disease-specific survival (P = .007), limited to the squamous cell carcinoma (SCC) histology subgroup (P < .001), where it was significant in both cohorts (University Hospital of North Norway, P = .003; Nordland Hospital, P = .022). Combining T CD45RO and stromal CD8(+) TIL density (S-CD8) increased the prognostic impact in SCC (P < .001) and showed a significant impact within all pathological stages (I, P = .025; II, P < .001; III, P = .001). In the multivariate analysis, T-CD45RO was an independent positive prognostic factor for SCC (hazard ratio 2.65, 95% confidence interval 1.64-4.28, P < .001), and in combination with S-CD8, the prognostic impact increased vastly (high + high versus low + low: hazard ratio 6.50, 95% confidence interval 3.54-11.91, P < .001). In conclusion, T-CD45RO was an independent prognostic factor for SCC NSCLC. When combined with S-CD8, the prognostic impact increased and was significant within each pathological stage. We propose CD45RO as a candidate marker for TNM-Immunoscore in SCC NSCLC. PMID- 26678913 TI - Kinetics of the Benzaldehyde-Inhibited Oxidation of Sulfite by Chlorine Dioxide. AB - There has been steady interest in the aqueous reaction of ClO2* with sulfur(IV) since the 1950s, and a wide variety of rate laws and mechanisms have been proposed. In neutral-to-alkaline media, the reaction is challenging to study because of its great rate. Here it is shown that benzaldehyde can be used as an additive to slow the reaction and make its rates more amenable to study. The rates can be quantitatively modeled by a mechanism that includes reversible binding of sulfur(IV) by benzaldehyde and a rate-limiting mixed second-order reaction of ClO2* with SO3(2-). The latter reaction occurs through parallel electron transfer from SO3(2-) to ClO2* and oxygen-atom transfer from ClO2* to SO3(2-). PMID- 26678912 TI - Prevalence of Intimate Partner Violence Among South Asian Women Living in Southern Ontario. AB - Intimate partner violence (IPV) affects 4 in 10 women in North America in their lifetime and 13-27 % in the past year. The basis for estimates stems largely from studies involving Caucasian women. Less is known about other minority populations such as South Asian women. This study aimed to assess the prevalence of IPV in the past year among South Asian women living in Southern Ontario. We conducted a survey of South Asian women living in Southern Ontario. All adult self-identified South Asian women attending a cultural event celebrating South Asian women who could understand English or Punjabi were eligible to participate. The survey contained three IPV prevalence questions adapted from the Woman Abuse Screening Tool. A total of 188 women (45 % of potentially eligible women) participated. Nearly 1 in 5 women reported IPV within the past year (19.3 %, 95 % CI 13.9-26.1 %). In this study single women were significantly more likely to have experienced IPV in the past year compared to married women (p = 0.035). Self-identified immigrant and non-immigrant South Asian women in this sample of women living in Southern Ontario experienced violence in proportions comparable to the general population. Programs for women should ensure accessibility and support of all ethnicities given equivalent rates of violence in the community. PMID- 26678914 TI - The role of synthetic drugs in the biologic era: therapeutic strategies for treating juvenile idiopathic arthritis. AB - INTRODUCTION: Juvenile idiopathic arthritis is the most frequent chronic rheumatic disease in childhood. Synthetic disease modifying drugs (DMARDs) have been used in its treatment since the 1980s and have led to substantial improvement of quality of life and disease outcome. Recent pharmacological research has focused on newer medications, especially biologic agents. AREAS COVERED: Synthetic DMARDS, especially methotrexate, rightfully remain the first line treatment of most categories of juvenile arthritis, as attested by several international guidelines. A substantial body of evidence supports these medications, and recent research tries to clarify their optimal use in the clinical setting, both as monotherapy and in combination with biologics. In addition, new forms of synthetic DMARDs are in the research pipeline, or are already used for rheumatoid arthritis. EXPERT OPINION: Methotrexate remains the preferred first-line medication for polyarticular arthritis, with leflunomide as a viable alternative in case of intolerance or toxicity, despite lack of approval in Europe and the US. Sulfasalazine and hydroxychloroquine are used only rarely in clinical practice, considered in combination with methotrexate if biologics are not available. New synthetic DMARDS are in the research pipeline for JIA, in the form of small molecules. PMID- 26678915 TI - The Active Metabolite of Vitamin D3 as a Potential Immunomodulator. AB - In the past, vitamin D was known for its classical, skeletal action as a regulator of calcium and bone homoeostasis. Currently, vitamin D was found to have a role in numerous physiological processes in the human body; thus, vitamin D has pleiotropic activity. The studies carried out in the past two decades showed the role of vitamin D in the regulation of immune system functions. Basically, these effects may be mediated not only via endocrine mechanism of circulating calcitriol but also via paracrine one (based on cell-cell communication that leads to production of signal inducing the changes in nearby/adjacent cells and modulating their differentiation or behaviour) and intracrine mechanism (the action of vitamin D inside a cell) of 1,25 dihydroxycholecalciferol (1,25(OH)2 D3 ) synthetized from its precursor 25 hydroxyvitamin D3 (25(OH)D3 ). Both vitamin D receptor (VDR) and 25 hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are expressed in several types of immune cells (i.e. antigen presenting cells, T and B cells), and thus, they are able to synthetize the bioactive form of vitamin D that modulates both the innate and adaptive immune system. This review discusses the role of vitamin D as regulator of immune system, and our understanding of how vitamin D regulates both adaptive and innate immunity as well as inflammatory cascade on the cellular level. PMID- 26678916 TI - Magnifying the Scale of Visual Biofeedback Improves Posture. AB - Biofeedback has been shown to minimize body sway during quiet standing. However, limited research has reported the optimal sensitivity parameters of visual biofeedback related to the center of pressure (COP) sway. Accordingly, 19 young adults (6 males; 13 females; aged 21.3 +/- 2.5) stood with feet together and performed three visual biofeedback intensities [unmodified biofeedback (UMBF), BF magnified by 5 (BF5), BF magnified by 10 (BF10)], along with control trials with no biofeedback (NBF). The participants were instructed to stand as still as possible while minimizing the movements of the visual target. The findings revealed that UMBF produced significantly greater COP displacement in both the anterior-posterior (AP) and medial-lateral directions, as well as greater standard deviation of the COP in the AP direction (p < 0.05). Additionally, NBF showed significantly greater 95 % area ellipse than the UMBF, BF5, and BF10 intensities (p < 0.001). Therefore, the most sensitive COP scales generated the least amount of postural sway. However, there were no significant differences on any of the COP measures between BF5 and BF10. This research provides insight with respect to the proper scale on which biofeedback should be given in order to improve postural control (i.e., BF5 or BF10). PMID- 26678917 TI - Disentangling the multigenic and pleiotropic nature of molecular function. AB - BACKGROUND: Biological processes at the molecular level are usually represented by molecular interaction networks. Function is organised and modularity identified based on network topology, however, this approach often fails to account for the dynamic and multifunctional nature of molecular components. For example, a molecule engaging in spatially or temporally independent functions may be inappropriately clustered into a single functional module. To capture biologically meaningful sets of interacting molecules, we use experimentally defined pathways as spatial/temporal units of molecular activity. RESULTS: We defined functional profiles of Saccharomyces cerevisiae based on a minimal set of Gene Ontology terms sufficient to represent each pathway's genes. The Gene Ontology terms were used to annotate 271 pathways, accounting for pathway multi functionality and gene pleiotropy. Pathways were then arranged into a network, linked by shared functionality. Of the genes in our data set, 44% appeared in multiple pathways performing a diverse set of functions. Linking pathways by overlapping functionality revealed a modular network with energy metabolism forming a sparse centre, surrounded by several denser clusters comprised of regulatory and metabolic pathways. Signalling pathways formed a relatively discrete cluster connected to the centre of the network. Genetic interactions were enriched within the clusters of pathways by a factor of 5.5, confirming the organisation of our pathway network is biologically significant. CONCLUSIONS: Our representation of molecular function according to pathway relationships enables analysis of gene/protein activity in the context of specific functional roles, as an alternative to typical molecule-centric graph-based methods. The pathway network demonstrates the cooperation of multiple pathways to perform biological processes and organises pathways into functionally related clusters with interdependent outcomes. PMID- 26678918 TI - Mono-Exponential Fitting in T2-Relaxometry: Relevance of Offset and First Echo. AB - INTRODUCTION: T2 relaxometry has become an important tool in quantitative MRI. Little focus has been put on the effect of the refocusing flip angle upon the offset parameter, which was introduced to account for a signal floor due to noise or to long T2 components. The aim of this study was to show that B1 imperfections contribute significantly to the offset. We further introduce a simple method to reduce the systematic error in T2 by discarding the first echo and using the offset fitting approach. MATERIALS AND METHODS: Signal curves of T2 relaxometry were simulated based on extended phase graph theory and evaluated for 4 different methods (inclusion and exclusion of the first echo, while fitting with and without the offset). We further performed T2 relaxometry in a phantom at 9.4T magnetic resonance imaging scanner and used the same methods for post-processing as in the extended phase graph simulated data. Single spin echo sequences were used to determine the correct T2 time. RESULTS: The simulation data showed that the systematic error in T2 and the offset depends on the refocusing pulse, the echo spacing and the echo train length. The systematic error could be reduced by discarding the first echo. Further reduction of the systematic T2 error was reached by using the offset as fitting parameter. The phantom experiments confirmed these findings. CONCLUSION: The fitted offset parameter in T2 relaxometry is influenced by imperfect refocusing pulses. Using the offset as a fitting parameter and discarding the first echo is a fast and easy method to minimize the error in T2, particularly for low to intermediate echo train length. PMID- 26678931 TI - ENSO Modulations due to Interannual Variability of Freshwater Forcing and Ocean Biology-induced Heating in the Tropical Pacific. AB - Recent studies have identified clear climate feedbacks associated with interannual variations in freshwater forcing (FWF) and ocean biology-induced heating (OBH) in the tropical Pacific. The interrelationships among the related anomaly fields are analyzed using hybrid coupled model (HCM) simulations to illustrate their combined roles in modulating the El Nino-Southern Oscillation (ENSO). The HCM-based supporting experiments are performed to isolate the related feedbacks, with interannually varying FWF and OBH being represented individually or collectively, which allows their effects to be examined in a clear way. It is demonstrated that the interannual freshwater forcing enhances ENSO variability and slightly prolongs the simulated ENSO period, while the interannual OBH reduces ENSO variability and slightly shortens the ENSO period, with their feedback effects tending to counteract each other. PMID- 26678919 TI - Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog. AB - Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 * 5 MUg/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. (c) 2015 American Society for Bone and Mineral Research. PMID- 26678932 TI - Chirality induction using circularly polarized light into a branched oligofluorene derivative in the presence of an achiral aid molecule. AB - Chirality induction into a uniform, star-shaped fluorene oligomer with a central truxene moiety (T3) was achieved using circularly polarized light in the presence of achiral fluorene or phenanthrene. Induction into T3 alone was difficult, suggesting that close chain packing realized through interactions of T3 with small molecules plays a role in chirality induction. PMID- 26678933 TI - Capturing Cd(ii) and Pb(ii) from contaminated water sources by electro-deposition on hydrotalcite-like compounds. AB - Two different hydrotalcite-like compounds were prepared and used as substrates for the electrochemical removal of extremely toxic pollutant cations, such as Cd(ii) and Pb(ii), from aqueous solutions, and their subsequent recovery for further potential applications. By deposition on the hydrotalcite electrode, it was possible to remove 75% of Cd(ii) contained in a starting 5.2 mM solution of CdCl2, which was subsequently recovered and concentrated up to 14.3 mM in a single step. A removal of almost 100% was obtained in the case of Pb(ii). Its recovery was largely hindered by the formation of several inert phases, among which is some stable formation of hydroxycarbonate. Our results suggest that the removal of these contaminants by hydrotalcite-like compounds occurs by the combination of two parallel processes: electro-deposition and adsorption. It was possible to achieve a removal capacity for Cd(ii) and Pb(ii) equal to 763 mg ga.m.(-1) and 1039 mg ga.m.(-1), respectively. These removal capacities, accompanied by an excellent posterior eluent-free recovery of Cd(ii), suggest that this new method could be an environmentally friendly alternative to the conventional adsorption wastewater treatment. PMID- 26678934 TI - Identification of genes associated with melanoma metastasis. AB - The aims of the study were to identify the differentially expressed genes (DEGs) between primary melanomas and metastasis melanomas (MMs), and to investigate the mechanisms of MMs. The microarray data GSE8401 including 31 primary melanomas and 52 MMs were downloaded from Gene Expression Omnibus. DEGs were identified using the Linear Models for Microarray Data package. The functional and pathway enrichment analyses were performed for DEGs. Identification of transcription factors, tumor-associated genes (TAGs), and tumor suppressor genes (TSGs) were performed with the TRANSFAC, TAG, and TSGene databases, respectively. A protein protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes. The modules construction and analysis was performed using Molecular Complex Detection and Gene Cluster with Literature Profiles, respectively. In total, 1004 upregulated and 1008 downregulated DEGs were identified. The upregulated DEGs, such as CDK1, BRCA1, MAD2L1, and PCNA, were significantly enriched in cell cycles, DNA replication, and mismatch repair. The downregulated DEGs, such as COLIAL, COL4A5, COL18A1, and LAMC2, were enriched in cell adhesion and extracellular matrix-receptor interaction. BRCA1 was identified as a transcription factor and TSG, and COL18A1 and LAMC2 were identified as a TSG and TAG, respectively. The upregulated DEGs had higher degrees in the protein protein interaction network and module, such as PCNA, CDK1, and MAD2L1, and the heat map showed they were clustered in the functions of cell cycle and division. These results may demonstrate the potential roles of DEGs such as CDK1, BRCA1, COL18A1, and LAMC2 in the mechanism of MM. PMID- 26678935 TI - Thallium-201 is comparable to technetium-99m-sestamibi for estimating cardiac function in patients with abnormal myocardial perfusion imaging. AB - We analyzed the left-ventricular functional data obtained by cardiac-gated single photon emission computed tomography myocardial perfusion imaging (MPI) with thallium-201 (Tl-201) and technetium-99m-sestamibi (MIBI) protocols in different groups of patients, and compared the data between Tl-201 and MIBI. Two hundred and seventy-two patients undergoing dipyridamole stress/redistribution Tl-201 MPI and 563 patients undergoing 1-day rest/dipyridamole stress MIBI MPI were included. Higher mean stress ejection fraction (EF), rest EF, and change in EF (DeltaEF) were noticed in the normal MPI groups by both Tl-201 and MIBI protocols. Higher mean EF was observed in the females with normal MPI results despite their higher mean age. Comparisons between the Tl-201 and MIBI groups suggested a significant difference in all functional parameters, except for the rest end diastolic volume/end systolic volume and DeltaEF between groups with negative MPI results. For the positive MPI groups, there was no significant difference in all parameters, except for the change in end diastolic volume and change in end systolic volume after stress between both protocols. The Tl-201 provides comparable left-ventricular functional data to MIBI cardiac-gated single photon emission computed tomography in patients with positive MPI results, and may therefore be undertaken routinely for incremental functional information that is especially valuable to this patient group. PMID- 26678936 TI - Standard percutaneous nephrolithotomy alone versus in combination with intraoperative anterograde flexible nephroscopy for staghorn stones: A retrospective study. AB - This study aimed to compare the outcomes of standard percutaneous nephrolithotomy (PCNL) to PCNL with intraoperative antegrade flexible nephroscopy (IAFN) for treating stones of staghorn nature. We retrospectively analyzed patients treated using PCNL between January 2007 and July 2013. A total of 1250 patients were treated using PCNL, and 166 patients had staghorn stones. All patients had been subjected to a complete blood count, routine biochemical analyses, coagulation tests, a complete urine analysis, and urine cultures. Patients with a positive urine culture had been treated with appropriate antibiotics until the urine culture became negative. After purchasing a flexible renoscope in March 2012, we routinely used this tool to improve the stone-free (SF) rate. The 105 patients who underwent standard PCNL prior to March 2012 were classified as Group 1, and the 61 patients who underwent PCNL + IAFN after that date were classified as Group 2. The two groups had similar and homogeneous demographic data. The fluoroscopy and total operative times were significantly higher in Group 2 than in Group 1 (p < 0.01). Additionally, the hospitalization time (p < 0.01) and the mean hematocrit decrease (p < 0.01) were significantly lower in Group 1. In both groups, the SF rates were higher than 85%, similar to those reported in the literature. Although Group 2 had a slightly better SF rates, this difference was not statistically significant. For staghorn calculi, PCNL combined with IAFN yields excellent outcomes. However, similar prospective studies on larger cohorts should be performed to support our findings. PMID- 26678937 TI - Intravenous paracetamol for relief of pain during transrectal-ultrasound-guided biopsy of the prostate: A prospective, randomized, double-blind, placebo controlled study. AB - Transrectal-ultrasound-guided prostate biopsy (TRUS-PBx) is the standard procedure for diagnosing prostate cancer. The procedure does cause some pain and discomfort; therefore, an adequate analgesia is necessary to ensure patient comfort, which can also facilitate good-quality results. This prospective, randomized, double-blinded, placebo-controlled study aimed to determine if intravenous (IV) paracetamol can reduce the severity of pain associated with TRUS PBx. The study included 104 patients, scheduled to undergo TRUS-PBx with a suspicion of prostate cancer, that were prospectively randomized to receive either IV paracetamol (paracetamol group) or placebo (placebo group) 30 minutes prior to TRUS-PBx. All patients had 12 standardized biopsy samples taken. Pain was measured using a 10-point visual analog pain scale during probe insertion, during the biopsy procedure, and 1 hour postbiopsy. All biopsies were performed by the same urologist, whereas a different urologist administered the visual analog pain scale. There were not any significant differences in age, prostate specific antigen level, or prostate volume between the two groups. The pain scores were significantly lower during probe insertion, biopsy procedure, and 1 hour postbiopsy in the paracetamol group than in the placebo group. In conclusion, the IV administration of paracetamol significantly reduced the severity of pain associated with TRUS-PBx. PMID- 26678939 TI - The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis. AB - Preliminary evidence suggests that a higher neutrophil-lymphocyte ratio (NLR) may be an indicator of active ulcerative colitis (UC). However, it is not clear whether the NLR is a useful and simple indicator of clinical activity in UC after adjusting for the other inflammatory markers. We designed a retrospective study to evaluate the role of the NLR in estimating disease severity in UC patients. The study consisted of 71 patients with UC and 140 age- and sex-matched healthy individuals (control group). The NLR, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count were measured. The NLR values of the active UC group were elevated compared with those of the patients with inactive UC and the controls (2.59 +/- 1.47, 2.03 +/- 1.07, and 1.98 +/- 0.85, respectively; p = 0.005). The receiver operating characteristic revealed that the optimum NLR cut off point for active UC was 2.39. A multivariable logistic analysis showed that of the parameters studied, C-reactive protein was the only parameter able to significantly discriminate active from inactive UC (B: 0.222; p = 0.017; odds ratio: 1.248; 95% confidence interval: 1.041-1.497). PMID- 26678938 TI - Propofol target-controlled infusion for sedated gastrointestinal endoscopy: A comparison of propofol alone versus propofol-fentanyl-midazolam. AB - Gastrointestinal (GI) endoscopy is the major technique for diagnosis of GI disease and treatment. Various sedation and analgesia regimens such as midazolam, fentanyl, and propofol can be used during GI endoscopy. The purpose of the study was to compare propofol alone and propofol combination with midazolam and fentanyl in moderate sedation for GI endoscopy. One hundred patients undergoing GI endoscopy were enrolled in this study. All patients received a propofol target controlled infusion (TCI) to maintain sedation during the procedure. Patients were randomly allocated into either Group P (propofol TCI alone) or Group C (combination of propofol TCI plus midazolam and fentanyl). Dermographic data, anesthetic parameters (sedation regimen, blood pressure, heart rate, and oxygen saturation), procedure parameters (procedure time, colonoscopy, or panendoscopy), propofol consumption, and adverse events (hypoxia, hypotension, and bradycardia) were all recorded. Postprocedural records included recovery time, postoperative adverse events (nausea, vomiting, dizziness, recall, and pain) and satisfaction. The average propofol consumption was 251 +/- 83 mg in Group P and 159 +/- 73 mg in Group C (p < 0.001). The incidence of transient hypotension was higher in Group P (p = 0.009). The recovery time and discharge time were both shorter in Group C (p < 0.001 and p = 0.006 respectively). Overall, postprocedural adverse events were similar in both groups. The postanesthetic satisfaction was comparable in both groups. TCI of propofol combined with midazolam and fentanyl achieved sedation with fewer hypotension episodes and shorter recovery and discharge time than propofol TCI alone in patients undergoing GI endoscopy. PMID- 26678940 TI - Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy. AB - Acute appendicitis (AA) is not uncommon during pregnancy but can be difficult to diagnose. This study evaluated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in addition to conventional diagnostic indicators of the disease to diagnose AA during pregnancy. Age, gestational age, white blood cell (WBC) count, Alvarado scores, C-reactive protein (CRP), lymphocyte count, NLR and PLR were compared among 28 pregnant women who underwent surgery for AA, 35 pregnant women wrongly suspected as having AA, 29 healthy pregnant women, and 30 nonpregnant healthy women. Mean WBC counts and CRP levels were higher in women with proven AA than in those of control groups (all p < 0.05). Among all the groups, the median NLR and PLR were significantly different in women with proven AA (all p < 0.05). Receiver operating characteristic analysis was used to determine cut-off values for WBC count, CRP, lymphocyte count, NLR and PLR, and multiple logistic regression analysis showed that NLR and PLR used with routine methods could diagnose AA with 90.5% accuracy. Used in addition to routine diagnostic methods, NLR and PLR increased the accuracy of the diagnosis of AA in pregnant women. PMID- 26678941 TI - The genotype distribution of hepatitis C in southeastern Taiwan: Clinical characteristics, racial difference, and therapeutic response. AB - The genotypes of hepatitis C virus (HCV) are associated with the therapeutic response. The racial diversity of Taitung, Taiwan is heterogeneous and a distinguishing feature; how such racial differences influence the genotype distribution and treatment outcome has not been well studied. The objective of this study is to elucidate the HCV genotype distribution in southeastern Taiwan and to analyze the racial differences influencing genotypes and clinical implications. In this retrospective cohort study, we included 343 patients who had been treated with peginterferon-alpha plus ribavirin. The predominant HCV genotype in the southeastern area was type 1 (43.7%), followed by type 2 (37.0%). The proportion of patients mixed with genotype 1 was lower in indigenous vis-a vis nonindigenous groups (46.1% and 60.2%, p = 0.02). The prevalence of genotype 6 (5.2%) seems higher than in the general population of Taiwan and showed no difference between indigenous and nonindigenous people. The sustained virological response rate was higher in patients without genotype 1, low baseline HCV RNA (<= 400,000 IU/mL), and in patients who achieved rapid virological response. Racial differences did not influence the therapeutic response. In this retrospective study, the proportion of HCV genotype 6 appeared slightly higher in southeastern areas than in the general population in Taiwan. The prevalence of genotype 1 in indigenous people was statistically lower than in nonindigenous people. Sustained virological response rate did not show any significant difference between indigenous and nonindigenous people in the current study. PMID- 26678942 TI - Acute transformation of chronic-type adult T-cell leukemia/lymphoma presenting with seizures. PMID- 26678943 TI - Role of the Interdomain Linker in RNA-Activated Protein Kinase Activation. AB - RNA-activated protein kinase (PKR) is a key component of the interferon-induced antiviral pathway in higher eukaryotes. Upon recognition of viral dsRNA, PKR is activated via dimerization and autophosphorylation. PKR contains two N-terminal dsRNA binding domains (dsRBD) and a C-terminal kinase domain. The dsRBDs and the kinase are separated by a long, unstructured ~80-amino acid linker in the human enzyme. The length of the N-terminal portion of the linker varies among PKR sequences, and it is completely absent in one ortholog. Here, we characterize the effects of deleting the variable region from the human enzyme to produce PKRDeltaV. The linker deletion results in quantitative but not qualitative changes in catalytic activity, RNA binding, and conformation. PKRDeltaV is somewhat more active and exhibits more cooperative RNA binding. As we previously observed for the full-length enzyme, PKRDeltaV is flexible in solution and adopts a range of compact and extended conformations. The conformational ensemble is biased toward compact states that might be related to weak interactions between the dsRBD and kinase domains. PKR retains RNA-induced autophosphorylation upon complete removal of the linker, indicating that the C-terminal, basic region is also not required for activity. PMID- 26678944 TI - A critical discourse analysis of the attitudes of occupational therapists and physiotherapists towards the systematic use of standardised outcome measurement. AB - PURPOSE: To investigate discourses relating to the implementation of standardised outcome measurement within rehabilitation practise. METHOD: It is a critical discourse analysis of texts in professional occupational therapist (OT) and physiotherapist (PT) journals, along with transcriptions from three focus group interviews with 25 OTs and PTs in local rehabilitation settings. RESULTS: Although positive attitudes towards outcome measurement were expressed in the professional journals, OTs and PTs in local settings had professional reservations about standardisation of the rehabilitation practise. The therapists were caught in what they considered to be a dilemma between taking a holistic approach and performing standardised practise. Systematic outcome measurement challenged the core values of their practise. Therapists often felt that 'it did not make sense' to use outcome measurement and this became a barrier to its implementation. CONCLUSION: If the use of standardised outcome measurement is to be increased, reflection is needed on how the measurements can be integrated to provide a meaningful contribution to individual rehabilitation processes. To optimise implementation, it is essential to make use of research in knowledge translation and adapt it to fit with the ways in which new ideas and recommendations are implemented in local rehabilitation contexts. Implications for Rehabilitation Successful implementation of standardised outcome measurements depends on whether occupational therapists and physiotherapists have an experience of the measurements as being meaningful. Enforcement of standardised outcome measurements must be done by means of more than a few isolated arguments, if professional acceptance is to be gained. To reject established dogmas on, e.g. standardisation, deliberate and conscious reflections in local settings are needed. It is necessary to go beyond normal and familiar professional reflections. To this end, newcomers' opinions are valuable. PMID- 26678946 TI - DNA-Directed Assembly of Nanogold Dimers: A Unique Dynamic Light Scattering Sensing Probe for Transcription Factor Detection. AB - We have developed a unique DNA-assembled gold nanoparticles (AuNPs) dimer for dynamic light scattering (DLS) sensing of transcription factors, exemplified by estrogen receptor (ER) that binds specifically to a double-stranded (ds) DNA sequence containing estrogen response element (ERE). Here, ERE sequence is incorporated into the DNA linkers to bridge the AuNPs dimer for ER binding. Coupled with DLS, this AuNP dimer-based DLS detection system gave distinct readout of a single 'complex peak' in the presence of the target molecule (i.e., ER). This unique signature marked the first time that such nanostructures can be used to study transcription factor-DNA interactions, which DLS alone cannot do. This was also unlike previously reported AuNP-DLS assays that gave random and broad distribution of particles size upon target binding. In addition, the ERE containing AuNP dimers could also suppress the light-scattering signal from the unbound proteins and other interfering factors (e.g., buffer background), and has potential for sensitive detection of target proteins in complex biological samples such as cell lysates. In short, the as-developed AuNP dimer probe coupled with DLS is a simple (mix and test), rapid (readout in ~5 min) and sensitive (low nM levels of ER) platform to detect sequence-specific protein-DNA binding event. PMID- 26678947 TI - Augmented reality, virtual reality and gaming: an integral part of nursing. PMID- 26678948 TI - Trends in surgical management and pre-operative urodynamics in female medicare beneficiaries with mixed incontinence. AB - OBJECTIVE: We sought to examine the surgical trends and utilization of treatment for mixed urinary incontinence among female Medicare beneficiaries. METHODS: Data was obtained from a 5% national random sample of outpatient and carrier claims from 2000 to 2011. Included were female patients 65 and older, diagnosed with mixed urinary incontinence, who underwent surgical treatment identified by Current Procedural Terminology, Fourth Edition (CPT-4) codes. Urodynamics (UDS) before initial and secondary procedure were also identified using CPT-4 codes. Procedural trends and utilization of UDS were analyzed. RESULTS: Utilization of UDS increased during the study period, from 38.4% to 74.0% prior to initial surgical intervention, and from 28.6% to 62.5% preceding re-intervention. Sling surgery (63.0%) and injectable bulking agents (28.0%) were the most common surgical treatments adopted, followed by sacral nerve stimulation (SNS) (4.8%) and Burch (4.0%) procedures. Re-intervention was performed in 4.0% of patients initially treated with sling procedures and 21.3% of patients treated with bulking agents, the majority of whom (51.7% and 76.3%, respectively) underwent injection of a bulking agent. Risk of re-intervention was not different among those who did or did not receive urodynamic tests prior to the initial procedure (8.5% vs. 9.3%) CONCLUSIONS: Sling and bulk agents are the most common treatment for MUI. Preoperative urodynamic testing was not related to risk of re intervention following surgery for mixed urinary incontinence in this cohort. Neurourol. Urodynam. 36:422-425, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26678949 TI - Effects of storage on mixed-culture biological electrodes. AB - Storage methods are important to preserve the viability and biochemical characteristics of microbial cultures between experiments or during periods when bioreactors are inactive. Most of the research on storage has focused on isolates; however, there is an increasing interest in methods for mixed cultures, which are of relevance in environmental biotechnology. The purpose of this study was to investigate the effect of different storage methods on electrochemically active enrichment cultures. Acetate-oxidizing bioanodes generating a current density of about 5 A m(-2) were enriched in a microbial electrolysis cell. The effect of five weeks of storage was evaluated using electrochemical techniques and microbial community analysis. Storage by refrigeration resulted in quicker re activation than freezing in 10% glycerol, while the bioelectrochemical activity was entirely lost after storage using dehydration. The results showed that the bioelectrochemical activity of bioanodes stored at low temperature could be retained. However, during the re-activation period the bioanodes only recovered 75% of the current density generated before storage and the bacterial communities were different in composition and more diverse after storage than before. PMID- 26678950 TI - Novel mechanism of harmaline on inducing G2/M cell cycle arrest and apoptosis by up-regulating Fas/FasL in SGC-7901 cells. AB - Harmaline (HAR), a natural occurrence beta-carboline alkaloid, was isolated from the seeds of Peganum harmala and exhibited potent antitumor effect. In this study, the anti-gastric tumor effects of HAR were firstly investigated in vitro and in vivo. The results strongly showed that HAR could inhibit tumor cell proliferation and induce G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. HAR could up-regulate the expressions of cell cycle-related proteins of p-Cdc2, p21, p-p53, Cyclin B and down-regulate the expression of p-Cdc25C. In addition, HAR could up-regulate the expressions of Fas/FasL, activated Caspase-8 and Caspase-3. Moreover, blocking Fas/FasL signaling could markedly inhibit the apoptosis caused by HAR, suggesting that Fas/FasL mediated pathways were involved in HAR-induced apoptosis. Interestingly, HAR could also exert on antitumor activity with a dose of 15 mg/kg/day in vivo, which was also related with cell cycle arrest. These new findings provided a framework for further exploration of HAR which possess the potential antitumor activity by inducing cell cycle arrest and apoptosis. PMID- 26678951 TI - Association between rs1801133 polymorphism and risk of adult ischemic stroke: Meta-analysis based on case-control studies. AB - BACKGROUND: This study is aimed to quantify the strength of the association between rs1801133 polymorphism and ischemic stroke risk. METHODS: We have searched Medline, Springer, and Embase for studies investigating the association between rs1801133 polymorphism and ischemic stroke risk. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. RESULTS: Forty case-control studies comprising 8809 cases and 9130 controls are eligible for this meta-analysis on the basis of relation of rs1801133 polymorphism to ischemic stroke risk. Hardy-Weinberg equilibrium was used to perform in controls for excluding articles. The overall analysis suggested that rs1801133 polymorphism was associated with increased risk of ischemic stroke (ORT versus C=1.16, 95% CI 1.10-1.22; ORTT versus TC+CC=1.32, 95% CI 1.18-1.47; ORTT+TC versus CC=1.11, 95% CI 1.04-1.18). Subgroup analysis showed that T allele was a significant strength between T allele and stroke risk in Asian, Caucasian, male and young-middle populations (OR=1.19, 1.11, 1.30, 1.16, respectively). Compared with TC+CC, TT genotype was found to be a risk factor for developing ischemic stroke in Asian, Caucasian and male (OR=1.41, 1.20, 1.77, respectively). Additionally, TT+TC retained a significant increase for ischemic stroke only in Asian comparable to CC genotype (OR=1.14). CONCLUSIONS: The rs1801133 polymorphism could be capable of increasing ischemic stroke susceptibility in Asian, male and young-middle populations. PMID- 26678952 TI - Popes convict dead Pope Twice! The unbelievable Cadaver Synod. AB - In 897, the 9-month-old corpse of the late Pope Formosus stood trial by the reigning pontiff, Stephen VII. Stephen VII convicted Formosus, sentenced the cadaveric Pope to have three fingers of his right hand amputated and then had him buried in a common grave. This posthumous trial raised theological and sacramental debates and created an outrage in Rome that became the cause of Stephen VII's swift downfall. Pope Formosus joins other notable historical figures such as St. Thomas Becket and John Wycliffe who were tried and punished after death. PMID- 26678953 TI - Preoperative International Prostate Symptom Score Predictive of Inguinal Hernia in Patients Undergoing Robotic Prostatectomy. AB - PURPOSE: Studies have shown that encountering an inguinal hernia during robotic radical prostatectomy is not uncommon. We reviewed our experience with simultaneous robotic prostatectomy and mesh hernia repair to identify variables predictive of a hernia. MATERIALS AND METHODS: Our cohort consisted of 693 consecutive men who underwent robotic radical prostatectomy as performed by 1 surgeon. Hernias were repaired with mesh composed of equal parts of absorbable polyglecaprone-25 and nonabsorbable polypropylene monofilament. Preoperative variables potentially predictive of an inguinal hernia were evaluated. RESULTS: Inguinal hernias were encountered in 55 of 639 patients (8.6%), of which 22.3% were bilateral for a total of 68 hernia sides. Only 26 of 55 hernias (47.2%) were evident preoperatively. Men with a preoperative I-PSS (International Prostate Symptom Score) of 15 or greater had a 22.4% chance (30 of 134) of requiring a hernia repair compared with 5% in those without such a score (OR 5.54, 95% CI 3.13-9.81, p <0.0001). There were no differences between the hernia and nonhernia groups in prostate size, body mass index, age, blood loss, transfusions, operative time, length of stay or any Clavien grade II-V complication. In 47 patients there was 1 recurrence at a median followup of 27.9 months. There were no cases of mesh associated pain or erosion. CONCLUSIONS: Independent of prostate size, men with preoperative lower urinary tract dysfunction were at 5 times the risk of a hernia at robotic radical prostatectomy (22.4% vs 5%). Given that half of the hernias were subclinical, patients with an I-PSS of 15 or greater should be counseled about the potential need for hernia repair at robotic radical prostatectomy. PMID- 26678954 TI - The Effect of Start and Stop Age at Screening on the Risk of Being Diagnosed with Prostate Cancer. AB - PURPOSE: We investigated the effect of age and number of screens on the risk of prostate cancer diagnosis. MATERIALS AND METHODS: Since 1995 the Goteborg randomized population based prostate cancer screening trial has invited men biennially for prostate specific antigen testing, until the upper age limit of 70 years. Men with a prostate specific antigen above the threshold of 2.5 ng/ml were recommended further evaluation including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born between 1930 and 1943 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3 to 9 invitations). The cumulative incidence of prostate cancer was calculated using standard methods. RESULTS: Of the 3,488 (38%) complete attendees 667 were diagnosed with prostate cancer (followup 1995 to June 30, 2014). At age 70 years there was no significant difference in prostate cancer risk among those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of prostate cancer diagnosis increased dramatically with age, and was 7.9% at age 60, 15% at age 65 and 21% at age 70 for men who had been screened 4 or more times. CONCLUSIONS: There was no clear association between risk of prostate cancer and the number of screens. Starting screening at an early age appears to advance the time of prostate cancer diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with prostate cancer. PMID- 26678955 TI - Time Trends in Histological Features of Latent Prostate Cancer in Japan. AB - PURPOSE: The incidence of prostate cancer is reported to be increasing in Asia, including Japan. Although this trend has been attributed partly to a more Western diet, this assumption may involve variable confounders. Thus, we examined the histological features of contemporary vs historical latent prostate cancer. MATERIALS AND METHODS: Prostate specimens from a consecutive autopsy series (127, present study, 2008 to 2013) were examined. Each prostate gland was fixed and sliced in step sections. The findings were compared to those from another autopsy series (501 subjects, 1983 to 1987) at our institution. RESULTS: The mean age of subjects in the present study was 68.9 years while the mean age was not available from the earlier study. However, the mean age of the 566 entrants in the expanded database (1983 to 1989) was 63.5 years (p=0.0001). Prostate weight was significantly greater in the present study (p <0.0001). Latent prostate cancer was found more frequently in the present study than in the previous study (43.3% and 20.8%, respectively, p <0.0001). No distinct difference was seen in the proportion of tumor grade between the groups. An increasing trend of moderately to poorly differentiated tumors with advancing age was more evident in the present study. Index cancer volume was greater in the present study with 25.5% measuring 500 mm(3) or greater vs only 9.6% of cancers in the previous study (p=0.008). CONCLUSIONS: Chronological changes in the histological characteristics of Japanese latent prostate cancer were noted as it is more prevalent in the contemporary series. Our data may reflect a worldwide trend in increasingly aging societies. PMID- 26678956 TI - Time Course of Incident Adverse Experiences Associated with Doxazosin, Finasteride and Combination Therapy in Men with Benign Prostatic Hyperplasia: The MTOPS Trial. AB - PURPOSE: We examined first (incident) reports of selected adverse experiences associated with medical therapy in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: We studied the 6 most common adverse experiences, including nonsexual function related experiences (dizziness, orthostatic hypotension and weakness) and sexual function related experiences (impotence, decreased libido and abnormal ejaculation) reported in the MTOPS (Medical Therapy of Prostatic Symptoms) Study. A total of 3,047 men were randomized to placebo, doxazosin, finasteride or combination therapy and followed for a mean duration of 4.5 years. We compared the incidence rates of adverse experiences at year 1 to the rates thereafter. RESULTS: For each assigned treatment group, the incidence rates were significantly higher for all 6 adverse experiences examined at year 1 compared with the rates thereafter. Men assigned to combination therapy experienced the highest rates at year 1 with rates 3.4-fold to 10.6-fold higher than rates after year 1. The incidence rates for orthostatic hypotension and dizziness were significantly higher in the doxazosin and combination therapy groups compared with the placebo group at year 1. The incidence rates of the 3 examined sexual function related adverse experiences were significantly higher in the finasteride and combination therapy groups than in the placebo group at year 1. CONCLUSIONS: Rates of the first report of sexual function related and other adverse experiences associated with doxazosin, finasteride and combination therapy were greatest during year 1 of treatment. These patterns should be considered by patients and physicians when treatment for lower urinary tract function is initiated with these drugs. PMID- 26678957 TI - Urachal Carcinoma of the Bladder: Impact of Clinical and Immunohistochemical Parameters on Prognosis. AB - PURPOSE: Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to that of primary bladder and colorectal adenocarcinoma. The aim of this study was to explore the expression and prognostic relevance of 6 select protein markers of urachal carcinoma of the bladder, including p53, Ki67, RHAMM, BGN, IMP3 and MMP-7, which were formerly shown to be prognostic in urothelial carcinoma and colorectal adenocarcinoma. MATERIALS AND METHODS: Clinical and followup data were obtained on a total of 26 patients with urachal carcinoma of the bladder treated at 2 university hospitals. Immunohistochemical analysis of p53, Ki67, RHAMM, BGN, IMP3 and MMP-7 expression was performed in samples from 15 patients. Clinicopathological parameters and immunohistochemical results were tested for prognostic value on univariable and multivariable analyses. RESULTS: Followup was 50 months. Five-year overall and progression-free survival was 46% and 32%, respectively. On multivariable analysis a positive resection margin was an independent predictor of poor overall survival (p = 0.025). RHAMM (p = 0.0431), IMP3 (p = 0.0052), Ki67 (p = 0.0006) and p53 (p = 0.0024) expression rates were significantly increased in urachal carcinoma of the bladder cells compared to normal urothelium. IMP3 was elevated in Sheldon tumor stage IIIA compared to IIIB or greater (p = 0.0048). None of the analyzed protein markers was associated with survival. CONCLUSIONS: The independent prognostic value of a positive resection margin underlines the importance of complete surgical removal of urachal carcinoma of the bladder combined with en bloc resection of the median umbilical ligament and umbilicus. Our results in a limited number of samples show that Ki67, p53, RHAMM and IMP3 expression is enhanced but has no prognostic significance in urachal carcinoma of the bladder. PMID- 26678959 TI - Web-Based and Mobile Delivery of an Episodic Future Thinking Intervention for Overweight and Obese Families: A Feasibility Study. AB - BACKGROUND: The bias toward immediate gratification is associated with maladaptive eating behaviors and has been cross-sectionally and prospectively related to obesity. Engaging in episodic future thinking, which involves mental self-projection to pre-experience future events, reduces this bias and energy intake in overweight/obese adults and children. To examine how episodic future thinking can be incorporated into clinical interventions, a Web-based system was created to provide training for adults and children in their everyday lives. OBJECTIVE: Our study examined the technical feasibility, usability, and acceptability of a Web-based system that is accessible by mobile devices and adapts episodic future thinking for delivery in family-based obesity interventions. METHODS: We recruited 20 parent-child dyads (N=40) from the surrounding community and randomized to episodic future thinking versus a nutritional information thinking control to test the feasibility of a 4-week Web based intervention. Parents were 44.1 (SD 7.8) years of age with BMI of 34.2 (SD 6.8) kg/m(2). Children were 11.0 (SD 1.3) years of age with BMI percentile of 96.0 (SD 1.8). Families met weekly with a case manager for 4 weeks and used the system daily. Adherence was collected through the Web-based system, and perceived acceptance of the Web-based system was assessed postintervention. Measurements of body composition and dietary intake were collected at baseline and after the 4 weeks of intervention. RESULTS: All 20 families completed the intervention and attended all sessions. Results showed parents and children had high adherence to the Web-based system and perceived it to be easy to use, useful, and helpful. No differences between conditions were found in adherence for parents (P=.65) or children (P=.27). In addition, results suggest that basic nutrition information along with episodic future thinking delivered through our Web-based system may reduce energy intake and weight. CONCLUSIONS: We showed that our Web-based system is an accepted technology and a feasible utility. Furthermore, results provide initial evidence that our system can be incorporated into family-based treatments targeting behaviors related to weight control. These results show promising utility in using our Web-based system in interventions. PMID- 26678961 TI - Automated high-throughput dense matrix protein folding screen using a liquid handling robot combined with microfluidic capillary electrophoresis. AB - Modern molecular genetics technology has made it possible to swiftly sequence, clone and mass-produce recombinant DNA for the purpose of expressing heterologous genes of interest; however, recombinant protein production systems have struggled to keep pace. Mammalian expression systems are typically favored for their ability to produce and secrete proteins in their native state, but bacterial systems benefit from rapid cell line development and robust growth. The primary drawback to prokaryotic expression systems are that recombinant proteins are generally not secreted at high levels or correctly folded, and are often insoluble, necessitating post-expression protein folding to obtain the active product. In order to harness the advantages of prokaryotic expression, high throughput methods for executing protein folding screens and the subsequent analytics to identify lead conditions are required. Both of these tasks can be accomplished using a Biomek 3000 liquid handling robot to prepare the folding screen and to subsequently prepare the reactions for assessment using Caliper microfluidic capillary electrophoresis. By augmenting a protein folding screen with automation, the primary disadvantage of Escherichia coli expression has been mitigated, namely the labor intensive identification of the required protein folding conditions. Furthermore, a rigorous, quantitative method for identifying optimal protein folding buffer aids in the rapid development of an optimal production process. PMID- 26678962 TI - Quantitative trait loci underlying host responses of soybean to Fusarium virguliforme toxins that cause foliar sudden death syndrome. AB - KEY MESSAGE: Soybean deploys multiple genetic mechanisms to confer tolerance to Fusarium virguliforme toxins. This study revealed that F. virguliforme culture filtrates could be used in mapping QTL underlying foliar SDS resistance. Sudden death syndrome (SDS) is a major soybean disease throughout most of the soybean growing regions in the world including the United States. The disease is caused by the fungal pathogen, Fusarium virguliforme (Fv). The fungus produces several toxins that are responsible for development of interveinal leaf chlorosis and necrosis, which are typical foliar SDS symptoms. Growing of resistant cultivars has been the most effective method in controlling the disease. The objective of the present study was to identify quantitative trait loci (QTL) underlying host responses of soybean to Fv toxins present in culture filtrates. To accomplish this objective, two recombinant inbred line (RIL) populations, AX19286 (A95 684043 * LS94-3207) and AX19287 (A95-684043 * LS98-0582), segregating for SDS resistance were evaluated for foliar symptom development by applying two screening protocols, the stem cutting and the root feeding assays. The AX19286 population revealed two major and seven minor QTL for SDS resistance. In the AX19287 population, we identified five major QTL and three minor QTL. The two QTL mapped to Chromosome 7 [molecular linkage group (MLG) M] and Chromosome 20 (MLG I) are most likely novel, and were detected through screening of the AX19287 population with stem cutting and root feeding assays, respectively. This study established that Fv culture filtrates could be employed in mapping QTL underlying foliar SDS resistance. The outcomes of the research also suggest that multiple genetic mechanisms might be used by soybean to overcome the toxic effects of the toxins secreted by the pathogen into culture filtrates. PMID- 26678960 TI - PRINT: A Protein Bioconjugation Method with Exquisite N-terminal Specificity. AB - Chemical conjugation is commonly used to enhance the pharmacokinetics, biodistribution, and potency of protein therapeutics, but often leads to non specific modification or loss of bioactivity. Here, we present a simple, versatile and widely applicable method that allows exquisite N-terminal specific modification of proteins. Combining reversible side-chain blocking and protease mediated cleavage of a commonly used HIS tag appended to a protein, we generate with high yield and purity exquisitely site specific and selective bio-conjugates of TNF-alpha by using amine reactive NHS ester chemistry. We confirm the N terminal selectivity and specificity using mass spectral analyses and show near complete retention of the biological activity of our model protein both in vitro and in vivo murine models. We believe that this methodology would be applicable to a variety of potentially therapeutic proteins and the specificity afforded by this technique would allow for rapid generation of novel biologics. PMID- 26678963 TI - Polyoxometalate-based homochiral metal-organic frameworks for tandem asymmetric transformation of cyclic carbonates from olefins. AB - Currently, great interest is focused on developing auto-tandem catalytic reactions; a substrate is catalytically transferred through mechanistically distinct reactions without altering any reaction conditions. Here by incorporating a pyrrolidine moiety as a chiral organocatalyst and a polyoxometalate as an oxidation catalyst, a powerful approach is devised to achieve a tandem catalyst for the efficient conversion of CO2 into value-added enantiomerically pure cyclic carbonates. The multi-catalytic sites are orderly distributed and spatially matched in the framework. The captured CO2 molecules are synergistically fixed and activated by well-positioned pyrrolidine and amine groups, providing further compatibility with the terminal W=O activated epoxidation intermediate and driving the tandem catalytic process in a single workup stage and an asymmetric fashion. The structural simplicity of the building blocks and the use of inexpensive and readily available chemical reagents render this approach highly promising for the development of practical homochiral materials for CO2 conversion. PMID- 26678964 TI - Perspectives, Progress, and Opportunities for Palliative Care in Oncology. PMID- 26678965 TI - Integrating Palliative Care Into Oncology: A Way Forward. AB - BACKGROUND: Patients with cancer have complex physical, psychosocial, and spiritual needs that evolve throughout their disease trajectory. As patients are living longer with a diagnosis of cancer, the need is growing to address the morbidity due to the underlying illness as well as treatment-related adverse events. Palliative care includes treating physical symptoms as well as addressing psychosocial and spiritual needs. When these needs are addressed, the quality of care improves, costs decrease, and goals are aligned between the medical care provided and the patient and family. However, how best to integrate palliative care into oncology care is still an area of investigation. METHODS: The authors conducted a literature search, including randomized clinical trials and practice reviews, to evaluate the evidence for integrating palliative care into oncology care. Barriers to integration as well as sustainable paths forward are highlighted. The authors also utilize case studies as representative examples of integration. RESULTS: Current studies demonstrate that integrating palliative care into oncology care improves symptom control, rates of patient and family satisfaction, and quality of end-of-life care. However, for systemwide integration to be successful, commitment must be made to quality improvement, an infrastructure must be built to support palliative care screening, assessment, and intervention, and stakeholders must be engaged in the program. In addition, value must be demonstrated using metrics that affect quality, care utilization, and patient satisfaction. CONCLUSIONS: Even though most US cancer centers have a palliative care program, palliative care remains limited in scope. An integrated approach for palliative care with oncology care requires a systems-based approach, with agreement between all parties on shared common metrics for value. PMID- 26678966 TI - Improving the Quality of Palliative Care Through National and Regional Collaboration Efforts. AB - BACKGROUND: The measurement and reporting of the quality of care in the field of palliation has become a required task for many health care leaders and specialists in palliative care. Such efforts are aided when organizations collaborate together to share lessons learned. METHODS: The authors reviewed examples of quality-improvement collaborations in palliative care to understand the similarities, differences, and future directions of quality measurement and improvement strategies in the discipline. RESULTS: Three examples were identified that showed areas of robust and growing quality-improvement collaboration in the field of palliative care: the Global Palliative Care Quality Alliance, Palliative Care Quality Network, and Project Educate, Nurture, Advise, Before Life Ends. These efforts exemplify how shared-improvement activities can inform improved practice for organizations participating in collaboration. CONCLUSIONS: National and regional collaboratives can be used to enhance the quality of palliative care and are important efforts to standardize and improve the delivery of palliative care for persons with serious illness, along with their friends, family, and caregivers. PMID- 26678967 TI - Palliative Pharmacotherapy: State-of-the-Art Management of Symptoms in Patients With Cancer. AB - BACKGROUND: Advanced cancer produces multiple symptoms as patients progress through their disease trajectory. Identifying, measuring, and providing therapy for uncontrolled symptoms becomes important because disease-altering therapies may be no longer possible. Symptoms other than pain that cause distress in patients with cancer include delirium, dyspnea, anorexia, nausea, and fatigue. Precise management of these symptoms can lead to the best possible quality of life and lessen distress. This article reviews current management strategies of these symptoms. METHODS: The epidemiology, mechanisms, assessment, and therapies of common symptoms in the advanced cancer population are reviewed. RESULTS: Identifiable approaches facilitate symptom management in advanced illness. CONCLUSIONS: Using a systematic approach to symptoms in advanced illness can improve the quality of life and lessen distress among patients with cancer and their families, friends, and caregivers. PMID- 26678968 TI - Pharmacological Management of Cancer-Related Pain. AB - BACKGROUND: Pain occurs in 50% of patients with cancer at the time of diagnosis, and nearly 80% of patients with advanced stage cancer have moderate to severe pain. Assessment of pain requires the health care professional to measure pain intensity, delineate opioid responsiveness, and clarify the impact of pain on a patient's psychological, social, spiritual, and existential domains. To this end, the World Health Organization (WHO) has developed a 3-step pain ladder to help the health care professional effectively manage pain, classifying pain intensity according to severity and recommending analgesic agents based on their strength. METHODS: Health care professionals should follow the WHO guidelines to manage cancer-related pain in their patients. With regard to opioids, dosing, equianalgesic conversions, the management of adverse events, and the identification of new agents are discussed. Integrating adjuvant analgesics and interventional pain techniques into the management of cancer-related pain is also discussed. RESULTS: The WHO analgesic ladder is an effective tool for managing cancer-related pain. Successful pain management in patients with cancer relies upon the health care professional to pay attention to detail, especially during the introduction of new drugs and in identifying potential adverse events. Health care professionals must assess opioid responsiveness to determine whether adjuvant analgesics should also play a role in a patient's treatment plan. CONCLUSION: Adherence to the WHO pain ladder and understanding proper use of interventional pain techniques complement the pharmacological management of cancer-related pain. PMID- 26678969 TI - Clinical Implications of Opioid Pharmacogenomics in Patients With Cancer. AB - BACKGROUND: Pain can be a significant burden for patients with cancer and may have negative effects on their quality of life. Opioids are potent analgesics and serve as a foundation for pain management. The variation in response to opioid analgesics is well characterized and is partly due to genetic variability. METHODS: We reviewed the results of clinical studies to evaluate the relationships between genetic variants and select genes involved in the pharmacokinetics and pharmacodynamics of opioids, with an emphasis on patients with cancer. RESULTS: In patients with cancer-related pain, genetic variation in OPRM1, COMT, and ABCB1 is associated with response to morphine, which is the most well-studied opioid. Although it has not been studied in patients with cancer related pain, the effect of CYP2D6 variation is well characterized with codeine and tramadol. Evidence is limited for associating the genetic variation and pain response of oxycodone, hydrocodone, and fentanyl in patients with cancer. CONCLUSION: The clinical availability of pharmacogenomic testing and research findings related to these polymorphic genes suggest that genotyping patients for these genetic variants may allow health care professionals to better predict patient response to pain and, thus, personalize pain treatment. PMID- 26678970 TI - Palliative Sedation in Patients With Cancer. AB - BACKGROUND: Palliative sedation involves the use of sedative medication to relieve refractory symptoms in patients by reducing their level of consciousness. Although it is considered an acceptable clinical practice from most ethical points of view, palliative sedation is still a widely debated procedure and merits better understanding. METHODS: The relevant medical literature pertaining to palliative sedation was analyzed and reviewed from various technical, relational, and bioethical perspectives. RESULTS: Proportionate palliative sedation is considered to be the most clinically appropriate modality for performing palliative sedation. However, guidelines must be followed to ensure that it is performed correctly. Benzodiazepines represent the first therapeutic option and careful monitoring of dosages is essential to avoid oversedation or undersedation. CONCLUSIONS: Proportionate palliative sedation is used to manage and relieve refractory symptoms in patients with cancer during their last days or hours of life. Evidence suggests that its use has no detrimental effect on survival. A different decision-making process is used to manage the withdrawal of hydration than the process used to determine whether proportionate palliative sedation is appropriate. Communication between patients, their relatives, and the health care staff is important during this medical intervention. PMID- 26678971 TI - Integrating Psychosocial Care Into Routine Cancer Care. AB - BACKGROUND: Despite growing recognition that psychosocial care is an essential component of comprehensive cancer care, evidence suggests many patients with cancer do not receive needed psychosocial care. METHODS: Four areas were identified as potentially increasing the number of patients with cancer who receive needed psychosocial care: (1) formulating care standards, (2) issuing clinical practice guidelines, (3) developing and using measurable indicators of quality of care, and (4) demonstrating projects designed to improve the delivery of care. RESULTS: Standards for psychosocial care are identified, including a standard issued in 2015 by an accrediting organization. Three clinical practice guidelines for provisioning psychosocial care are also identified and reviewed. Methods for monitoring the quality of psychosocial care are characterized and the impact of monitoring changes in quality are evaluated in relation to existing evidence. Examples are provided of 2 large-scale efforts designed to improve the delivery of psychosocial care in community settings. CONCLUSIONS: Although considerable progress has been made in integrating psychosocial care into routine cancer care, work must still be done. Additional progress will be fostered by continued efforts to promote adherence to clinical practice guidelines and care standards for psychosocial care and by the development and dissemination of models that demonstrate how practices can implement these guidelines and standards. PMID- 26678972 TI - Systematic Review of Palliative Care in the Rural Setting. AB - BACKGROUND: Many of the world's population live in rural areas. However, access and dissemination of the advances taking place in the field of palliative care to patients living in rural areas have been limited. METHODS: We searched 2 large databases of the medical literature and found 248 relevant articles; we also identified another 59 articles through networking and a hand search of reference lists. Of those 307 articles, 39 met the inclusion criteria and were grouped into the following subcategories: intervention (n = 4), needs assessment (n = 2), program planning (n = 3), program evaluation (n = 4), education (n = 7), financial (n = 8), and comprehensive/systematic literature reviews (n = 11). RESULTS: We synthesized the current state of rural palliative care research and practice to identify important gaps for future research. Studies were conducted in the United States, Australia, Canada, Africa, Sweden, and India. Two randomized control trials were identified, both of which used telehealth approaches and had positive survival outcomes. One study demonstrated positive patient quality of life and depression outcomes. CONCLUSIONS: Research to guide rural palliative care practice is sparse. Approaches to telehealth, community- academic partnerships, and training rural health care professionals show promise, but more research is needed to determine best practices for providing palliative care to patients living in rural settings. PMID- 26678973 TI - New Frontiers in Outpatient Palliative Care for Patients With Cancer. AB - BACKGROUND: Although much evidence has accumulated demonstrating its benefit, relatively little is known about outpatient palliative care in patients with cancer. METHODS: This paper reviews the literature and perspectives from content experts to describe the current state of outpatient palliative care in the oncology setting and current areas of innovation and promise in the field. RESULTS: Evidence, including from controlled trials, documents the benefits of outpatient palliative care in the oncology setting. As a result, professional medical organizations have guidelines and recommendations based on the key role of palliative care in oncology. Six elements of the practice sit at the frontier of outpatient oncology palliative care, including the setting and timing of palliative care integration into outpatient oncology, the relationships between primary and specialty palliative care, quality and measurement, research, electronic and technical innovations, and finances. CONCLUSIONS: Evidence of clinical and health care system benefits supports the recommendations of professional organizations to integrate palliative care into the routine treatment of patients with advanced cancer. PMID- 26678974 TI - Palliative Care in Adolescents and Young Adults With Cancer. AB - BACKGROUND: Cancer survival rates for adolescents and young adults (AYA) have not improved over time relative to children or adults older than 39 years of age. Palliative care is specialized medical care focused on the control of symptoms and relief of suffering with the goal of improving quality of life for the patient and his or her family. To date, the integration of palliative care in AYA patients with cancer remains suboptimal. METHODS: We explore the role of palliative care in the continuum of clinical care for AYA patients with cancer. RESULTS: Clinical practice guidelines highlight the need for integrating palliative care for all patients with cancer, including the AYA population. Despite this, a paucity of evidence exists regarding the use of palliative care with AYA patients with cancer. Graduate clinical education represents an opportunity to promote the full inclusion and early integration of palliative care in the care of AYA patients with cancer. Advance care planning is one area where some agreement exists on the unique needs of AYA patients and their families. CONCLUSIONS: In general, palliative care is seen as being synonymous with end-of-life care for patients with cancer. However, the emerging trend toward standardizing oncology care to meet the unique medical, psychosocial, and supportive care needs of AYA patients with cancer and their families represents an opportunity for health care professionals to collaborate early with palliative care specialists to control symptoms and relieve suffering in this vulnerable population. PMID- 26678975 TI - Palliative Care in Older Patients With Cancer. AB - BACKGROUND: In general, cancer is a disease of aging, and palliative care is an essential step in the management of cancer in patients who are older. The goal of this article is to review common symptoms of cancer and oncology treatment and their management. METHODS: The pertinent medical literature was reviewed. RESULTS: The scope of palliative care includes personalized cancer treatment. This involves choosing treatment options that best fit the needs of each individual patient. Balancing treatment benefits and risks may be challenging in older patients, many of whom have limited life expectancies and decreased functional reserves. The benefits of treatment may diminish, and the risks of such treatment options increase with age. Thus, the first step toward personalized treatment includes determining physiological age, which is best estimated with a comprehensive geriatric assessment. Prevention of common complications, which include neutropenia and mucositis, allows the administration of treatment in full and effective doses. Fatigue is a chronic symptom related to cancer and its treatment and may lead to functional dependence and an increased risk of death. Fatigue might be prevented by daily exercise even during treatment. Other symptoms include pain and feelings of memory loss. CONCLUSIONS: The scope of palliative care encompasses more issues that symptom management and, for this reason, palliative care should be provided once the diagnosis of cancer is established. Determining treatment goals is essential to improve the treatment experience. Symptom management is similar in older and young patients, but symptoms in the older population may be associated with more frequent and severe complications. Many options exist to prevent and ameliorate the complications of oncology treatment in the aged. However, more studies should be conducted on the long-term care of older patients who have survived cancer. PMID- 26678977 TI - Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? AB - BACKGROUND: DOG1 is a novel gene on gastrointestinal stromal tumors (GISTs) that encodes the chloride channel protein anoctamin 1, also known as discovered on GIST-1 (DOG1) protein. DOG1 antibodies are a sensitive and specific marker against GIST positive for CD117 and CD34 and negative for CD117 and CD34. DOG1 is also independent of KIT or PDGFRA mutation status and considered specific for GIST when it was first discovered in 2004. METHODS: The previous 10 years of literature was searched for articles relating to DOG1. We critically reviewed 12 studies that showed DOG1 was positive in 250 cases of 2,360 tested non-GIST neoplasms (10.6%) at different anatomical sites using monoclonal, polyclonal, or nonspecified antibodies. Criteria for positivity varied between the studies. RESULTS: Monoclonal and polyclonal DOG1 antibodies were reactive in various different non-GIST tumor types spanning 9 organ systems in addition to normal salivary and pancreatic tissues. The tumors included were renal oncocytoma (100%), renal cell carcinoma chromophobe type (86%), solid pseudopapillary neoplasm of the pancreas (51%), neoplastic salivary tissue (17%), synovial sarcoma (15%), leiomyoma (10%), pancreatic adenocarcinoma (7%), and leiomyosarcoma (4%). CONCLUSIONS: By contrast to the original concept that DOG1 antibodies are specific to GIST neoplasms, the studies reviewed showed that the data suggest DOG1 positivity in select non-GIST tumors. Only in the appropriate clinical and pathological context is DOG1 positivity specific and helpful in the diagnosis of GIST. PMID- 26678976 TI - Prognostication of Survival in Patients With Advanced Cancer: Predicting the Unpredictable? AB - BACKGROUND: Prognosis is a key driver of clinical decision-making. However, available prognostication tools have limited accuracy and variable levels of validation. METHODS: Principles of survival prediction and literature on clinician prediction of survival, prognostic factors, and prognostic models were reviewed, with a focus on patients with advanced cancer and a survival rate of a few months or less. RESULTS: The 4 principles of survival prediction are (a) prognostication is a process instead of an event, (b) prognostic factors may evolve over the course of the disease, (c) prognostic accuracy for a given prognostic factor/ tool varies by the definition of accuracy, the patient population, and the time frame of prediction, and (d) the exact timing of death cannot be predicted with certainty. Clinician prediction of survival is the most commonly used approach to formulate prognosis. However, clinicians often overestimate survival rates with the temporal question. Other clinician prediction of survival approaches, such as surprise and probabilistic questions, have higher rates of accuracy. Established prognostic factors in the advanced cancer setting include decreased performance status, delirium, dysphagia, cancer anorexia-cachexia, dyspnea, inflammation, and malnutrition. Novel prognostic factors, such as phase angle, may improve rates of accuracy. Many prognostic models are available, including the Palliative Prognostic Score, the Palliative Prognostic Index, and the Glasgow Prognostic Score. CONCLUSIONS: Despite the uncertainty in survival prediction, existing prognostic tools can facilitate clinical decision-making by providing approximated time frames (months, weeks, or days). Future research should focus on clarifying and comparing the rates of accuracy for existing prognostic tools, identifying and validating novel prognostic factors, and linking prognostication to decision-making. PMID- 26678978 TI - Occurrence of Multiple Tumors in a Patient. AB - An 81-year-old man initially presented with a right forearm mass that was found to be myxofibrosarcoma. In addition, he was found to have gastric and intragastric masses identified as neuroendocrine tumor (NET) and gastrointestinal stromal tumor (GIST; presenting synchronously), respectively, as well as a new left upper quadrant mass identified as desmoid tumor in the colon. The patient complained of melena, which was found to be due to metastatic myxofibrosarcoma in the transverse colon. Several reports have associated GIST with NET and some reports have associated GIST with sarcomas and NET with sarcomas; however, this is the first report to document all these tumors in a single patient. Several factors may have contributed to the development of these tumors, including growth factors secreted by NET, KIT mutation of GIST predisposing to additional tumors, immunosuppressed state, or an underlying genetic syndrome. This case highlights the importance of investigating for additional malignancies when a primary malignancy is discovered. PMID- 26678979 TI - Association of Cancer Stem Cell Markers With Aggressive Tumor Features in Papillary Thyroid Carcinoma. AB - BACKGROUND: Identifying accurate prognostic molecular markers for papillary thyroid carcinoma (PTC) is important because many patients with PTC may be erroneously considered to have low-risk tumors. Evidence is also accumulating to support the existence of cancer stem cells in PTC. METHODS: Thirty controls and 167 patients with PTC were selected to establish a tissue microarray to investigate cancer stem cell marker expression in samples from an established pathological database. The protein expressions of CD44, CD133, epithelial cell adhesion molecule (EpCAM), CD45, and CD90 were evaluated by immunohistochemical assay in the tissue microarray. RESULTS: The protein levels of CD44, CD133, and EpCAM were significantly increased in PTC tissue compared with tissue from the controls. A positive correlation was found between cancer stem cell markers and tumor, node, and metastasis staging. CONCLUSIONS: Among a subset of patients with PTC, cancer stem cells detected by immunohistochemistry can be used as prognostic markers to screen for potential tumor dissemination. Whether these cancer stem cell markers are potentially therapeutic targets - and, thus, could be used for effective adjuvant treatment strategies - remains to be seen, and more data are needed. PMID- 26678980 TI - Should Vital Signs Be Routinely Obtained Prior to Intravenous Chemotherapy? Results From a 2-Center Study. AB - BACKGROUND: The American Society of Clinical Oncology and the Oncology Nursing Society have issued guidelines stating that the vital signs of patients should be routinely checked on days that intravenous chemotherapy is administered. This study sought evidence to justify this approach. METHODS: This trial focused on consecutive patients with cancer from 2 institutions and evaluated outcomes during the first cycle of gemcitabine-based chemotherapy. The primary end point of the study was a visit to the ED, hospitalization, or death during the first cycle of chemotherapy. RESULTS: Medical records from 1,158 patients were reviewed, and vital signs were checked in 589 patients on day 1 and in 486 on day 8. A total of 148 patients (12.8%) were evaluated in the emergency department (ED), 145 (12.5%) were hospitalized, and 11 (0.9%) died during their first cycle of chemotherapy. In multivariate analyses, which were adjusted for age, sex, cancer type, role of chemotherapy, number of chemotherapy drugs administered on day 1, and institution, checking vital signs on day 1 was associated with neither higher rates of ED visits nor with increased hospitalization; however, checking vital signs on day 8 was associated with higher rates of ED visits (odds ratio [OR]: 3.71; 95% confidence interval [CI]: 2.18-6.22; P < .0001) and higher rates of hospitalizations (OR: 3.98; 95% CI: 2.34-6.73; P < .0001). CONCLUSION: This study suggests a need for additional, evidence-based data to support the routine checking of vital signs prior to administering cancer chemotherapy. PMID- 26678981 TI - Advancing Cancer Control Through Research and Cancer Registry Collaborations in the Caribbean. AB - BACKGROUND: Few national registries exist in the Caribbean, resulting in limited cancer statistics being available for the region. Therefore, estimates are frequently based on the extrapolation of mortality data submitted to the World Health Organization. Thus, regional cancer surveillance and research need promoting, and their synergy must be strengthened. However, differences between countries outweigh similarities, hampering registration and availability of data. METHODS: The African-Caribbean Cancer Consortium (AC3) is a broad-based resource for education, training, and research on all aspects of cancer in populations of African descent. The AC3 focuses on capacity building in cancer registration in the Caribbean through special topics, training sessions, and biannual meetings. We review the results from selected AC3 workshops, including an inventory of established cancer registries in the Caribbean region, current cancer surveillance statistics, and a review of data quality. We then describe the potential for cancer research surveillance activities and the role of policymakers. RESULTS: Twelve of 30 Caribbean nations have cancer registries. Four of these nations provide high-quality incidence data, thus covering 14.4% of the population; therefore, regional estimates are challenging. Existing research and registry collaborations must pave the way and are facilitated by organizations like the AC3. CONCLUSIONS: Improved coverage for cancer registrations could help advance health policy through targeted research. Capacity building, resource optimization, collaboration, and communication between cancer surveillance and research teams are key to obtaining robust and complete data in the Caribbean. PMID- 26678982 TI - The readmission rate and medical cost of patients with schizophrenia after first hospitalization - A 10-year follow-up population-based study. AB - BACKGROUND: Hospital readmissions caused by relapse in patients with schizophrenia are associated with prognosis. Identifying individuals at high risk of readmission and providing interventions to lower the readmission rate are important. METHODS: Patients with schizophrenia who were hospitalized for the first time were recruited from the National Health Insurance Research Database from 2001 to 2010 (n=808, mean age 28.9years) and compared with matched controls. Data on the demographics, cost, and utilization of medical resources of patients who were readmitted were compared with non-readmitted patients. The readmission time curve was analyzed by the Kaplan-Meier method. RESULT: 570 (70.5%) patients were readmitted within 10years; the median time between admissions was 1.9years, and 25% of subjects were readmitted within 4months of the first hospitalization. There were no significant differences in age, gender, or length of hospitalization between the readmission and non-readmission groups. Taking into account all psychiatric medical services, the readmission group had a significantly higher mean frequency of care and a greater medical cost than the non-readmission group and matched controls. However, there were no significant differences with regard to non-psychiatric medical services. CONCLUSION: Schizophrenia has a high rate of readmission and high medical cost in naturalistic settings. In addition to the traditional hospital-based treatment model for patients with schizophrenia, the development of an effective intervention program is important, especially in the early years of the disease. PMID- 26678983 TI - Longitudinal informed consent competency in stable community patients with schizophrenia: A one-week training and one-year follow-up study. AB - OBJECTIVE: This study explores the efficacy of a one-week informed consent information training process for improving competence to provide consent in stable community patients with schizophrenia over a one-year follow-up period. METHOD: A one-week training session designed to enhance competence to provide informed consent for research was conducted. The training was guided by a research protocol that provided detailed explanations of each major conceptual unit. Participants were followed for one year, and comprised 50 stable community outpatients with schizophrenia who were randomly assigned to either an intervention group (IG, n=33) or a control group (CG, n=17) that did not receive any training. The Chinese Mandarin MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) was used to assess competence for informed consent pre training (baseline), post-training (one week later), and at the end of one year. RESULTS: A repeated measures analysis comparing the IG and CG at pre-training, post-training and the one-year follow-up revealed significant improvements in the Understanding and Appreciation subscale following the one-week training. However, by the end of one year, scores returned to baseline levels, with the exception of the Appreciation subscale, which was below baseline. There were significant main effects across time on the Appreciation and Reasoning subscales, indicating considerable changes over time. The CG showed no significant changes from pre training to one week later or at one-year follow-up for all subscales. CONCLUSIONS: The capacities of understanding and appreciation can be improved in stable community patients with schizophrenia after one week of training; however, this training effect is not sustained one year later. The results suggest that more intensive or periodic trainings may be needed to maintain long-term competence levels in patients with schizophrenia, particularly with regard to their capacity to appreciate the nature and consequences of study participation. PMID- 26678985 TI - Migraine. Long screen time exposure could increase the risk of migraine. PMID- 26678984 TI - Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection. AB - Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (>= 20 ng/mL: 19.7% versus 8.8%, p = 0.027; >= 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men. PMID- 26678986 TI - Neurodevelopmental disorders. Altered epigenetic regulation in early development associated with schizophrenia. PMID- 26678987 TI - Current randomized control trials, observational studies and meta analysis in off pump coronary surgery. AB - The off-pump literature is divided into three eras: the "early phase" with results favouring off-pump surgery supported with randomized control trials (RCTs) mainly from Bristol, UK; an "intermediate phase" dominated by the results of the ROOBY trial and finally a more "contemporary phase" whereby the off/on pump argument is unsettled. Although the literature has failed to project an overall superiority of off-pump versus on-pump surgery, nevertheless, small randomized control trials and large meta-analysis studies are concluding that the incidence of a stroke is less than 1 % when an aortic off-pump techniques (especially the non-touch technique) are advocated in patients with diseased ascending aorta. Furthermore, off-pump combined with hybrid procedures may lead to a reduction of adverse outcome in the aged high-risk population with concomitant poor left ventricular function and co-morbidities.The current review attempts to bring an insight onto the last ten years knowledge on the on/off-pump debate, with an aim to draw some clear conclusions in order to allow practitioners to reflect on the subject. PMID- 26678988 TI - Implementing Tobacco Control Programs in Homeless Shelters: A Mixed-Methods Study. AB - Background Tobacco-related chronic diseases contribute significantly to the increased morbidity and mortality observed in the homeless population. Few homeless service settings address tobacco use among their clients. Method Directors and staff from emergency and transitional shelters in San Diego County completed a questionnaire on no-smoking policies and smoking cessation services and participated in in-depth, semistructured interviews to examine the barriers to and facilitators of implementing smoke-free policies and cessation services in their facilities. Results Facilities differed in outdoor restrictions around smoking: 61.5% reported having an outdoor designated smoking zone, and 25% reported having a campus-wide ban on smoking. About one-third of the facilities offered on-site resources for smoking cessation. Although directors and staff supported smoke-free policies, they reported that the increased resources needed to "police" the policy created barriers to implementation. Almost all directors and staff expressed interest in developing an on-site tobacco control program, but they reported that lack of expertise among staff posed challenges to implementing such a program. Conclusion Our findings suggest that for a tobacco control program to be effective in homeless shelters, it should include training and incentives for staff to implement smoke-free policies and cessation services. PMID- 26678989 TI - Increased norovirus activity was associated with a novel norovirus GII.17 variant in Beijing, China during winter 2014-2015. AB - BACKGROUND: Norovirus (NoV) is a leading cause of sporadic cases and outbreaks of acute gastroenteritis (AGE). Increased NoV activity was observed in Beijing, China during winter 2014-2015; therefore, we examined the epidemiological patterns and genetic characteristics of NoV in the sporadic cases and outbreaks. METHODS: The weekly number of infectious diarrhea cases reported by all hospitals in Beijing was analyzed through the China information system for disease control and prevention. Fecal specimens were collected from the outbreaks and outpatients with AGE, and GI and GII NoVs were detected using real time reverse transcription polymerase chain reaction. The partial capsid genes and RNA-dependent RNA polymerase (RdRp) genes of NoV were both amplified and sequenced, and genotyping and phylogenetic analyses were performed. RESULTS: Between December 2014 and March 2015, the number of infectious diarrhea cases in Beijing (10,626 cases) increased by 35.6% over that of the previous year (7835 cases), and the detection rate of NoV (29.8%, 191/640) among outpatients with AGE was significantly higher than in the previous year (12.9%, 79/613) (chi(2) = 53.252, P < 0.001). Between November 2014 and March 2015, 35 outbreaks of AGE were reported in Beijing, and NoVs were detected in 33 outbreaks, all of which belonged to the GII genogroup. NoVs were sequenced and genotyped in 22 outbreaks, among which 20 were caused by a novel GII.17 strain. Among outpatients with AGE, this novel GII.17 strain was first detected in an outpatient in August 2014, and it replaced GII.4 Sydney_2012 as the predominant variant between December 2014 and March 2015. A phylogenetic analysis of the capsid genes and RdRp genes revealed that this novel GII.17 strain was distinct from previously identified GII variants, and it was recently designated as GII.P17_GII.17. This variant was further clustered into two sub groups, named GII.17_2012 and GII.17_2014. During winter 2014-2015, GII.17_2014 caused the majority of AGE outbreaks in China and Japan. CONCLUSIONS: During winter 2014-2015, a novel NoV GII.17 variant replaced the GII.4 variant Sydney 2012 as the predominant strain in Beijing, China and caused increased NoV activity. PMID- 26678990 TI - Elevational trends in hydraulic efficiency and safety of Pinus cembra roots. AB - In alpine regions, elevational gradients in environmental parameters are reflected by structural and functional changes in plant traits. Elevational changes in plant water relations have also been demonstrated, but comparable information on root hydraulics is generally lacking. We analyzed the hydraulic efficiency (specific hydraulic conductivity k s, entire root system conductance K R) and vulnerability to drought-induced embolism (water potential at 50 % loss of conductivity Psi 50) of the roots of Pinus cembra trees growing along an elevational transect of 600 m. Hydraulic parameters of the roots were compared with those of the stem and related to anatomical traits {mean conduit diameter (d), wall reinforcement [(t/b)(2)]}. We hypothesized that temperature-related restrictions in root function would cause a progressive limitation of hydraulic efficiency and safety with increasing elevation. We found that both root k s and K R decreased from low (1600 m a.s.l.: k s 5.6 +/- 0.7 kg m(-1) s(-1) MPa(-1), K R 0.049 +/- 0.005 kg m(-2) s (-1) MPa(-1)) to high elevation (2100 m a.s.l.: k s 4.2 +/- 0.6 kg m(-1) s(-1) MPa(-1), K R 0.035 +/- 0.006 kg m(-2) s(-1) MPa(-1)), with small trees showing higher K R than large trees. k s was higher in roots than in stems (0.5 +/- 0.05 kg m(-1)s(-1)MPa(-1)). Psi 50 values were similar across elevations and overall less negative in roots (Psi 50 -3.6 +/- 0.1 MPa) than in stems (Psi 50 -3.9 +/- 0.1 MPa). In roots, large-diameter tracheids were lacking at high elevation and (t/b)(2) increased, while d did not change. The elevational decrease in root hydraulic efficiency reflects a limitation in timberline tree hydraulics. In contrast, hydraulic safety was similar across elevations, indicating that avoidance of hydraulic failure is important for timberline trees. As hydraulic patterns can only partly be explained by the anatomical parameters studied, limitations and/or adaptations at the pit level are likely. PMID- 26678991 TI - Herbivory strongly influences among-population variation in reproductive output of Lythrum salicaria in its native range. AB - Herbivory can negatively affect several components of plant reproduction. Yet, because of a lack of experimental studies involving multiple populations, the extent to which differences in herbivory contribute to among-population variation in plant reproductive success is poorly known. We experimentally determined the effects of insect herbivory on reproductive output in nine natural populations of the perennial herb Lythrum salicaria along a disturbance gradient in an archipelago in northern Sweden, and we quantified among-population differentiation in resistance to herbivory in a common-garden experiment in the same area. The intensity of leaf herbivory varied >500-fold and mean female reproductive success >400-fold among the study populations. The intensity of herbivory was lowest in populations subject to strong disturbance from ice and wave action. Experimental removal of insect herbivores showed that the effect of herbivory on female reproductive success was correlated with the intensity of herbivory and that differences in insect herbivory could explain much of the among-population variation in the proportion of plants flowering and seed production. Population differentiation in resistance to herbivory was limited. The results demonstrate that the intensity of herbivory is a major determinant of flowering and seed output in L. salicaria, but that differences in herbivory are not associated with differences in plant resistance at the spatial scale examined. They further suggest that the physical disturbance regime may strongly influence the performance and abundance of perennial herbs and patterns of selection not only because of its effect on interspecific competition, but also because of effects on interactions with specialized herbivores. PMID- 26678992 TI - Characterization of the transcriptional regulation of the tarIJKL locus involved in ribitol-containing wall teichoic acid biosynthesis in Lactobacillus plantarum. AB - Lactobacillus plantarum strains produce either glycerol (Gro)- or ribitol (Rbo) backbone wall teichoic acid (WTA) (Gro-WTA and Rbo-WTA, respectively). The strain WCFS1 has been shown to be able to activate the tarIJKL locus involved in Rbo-WTA synthesis when the tagD1F1F2 locus for Gro-WTA synthesis was mutated, resulting in switching of the native Gro-WTA into Rbo-WTA. Here, we identify a regulator involved in the WTA backbone alditol switching and activation of the tarIJKL locus. Promoter reporter assays of the tarI promoter (Ptar) demonstrated its activity in the Rbo-WTA-producing mutant derivative (DeltatagF1-2) but not in the parental strain WCFS1. An electrophoresis mobility shift assay using a Ptar nucleotide fragment showed that this fragment bound to Ptar-binding protein(s) in a cell-free extract of WCFS1. Three proteins were subsequently isolated using Ptar bound to magnetic beads. These proteins were isolated efficiently from the lysate of WCFS1 but not from the lysate of its DeltatagF1-2 derivative, and were identified as redox-sensitive transcription regulator (Lp_0725), catabolite control protein A (Lp_2256) and TetR family transcriptional regulator (Lp_1153). The role of these proteins in Ptar regulation was investigated by knockout mutagenesis, showing that the Deltalp_1153 mutant expressed the tarI gene at a significantly higher level, supporting its role as a repressor of the tarIJKL locus. Notably, the Deltalp_1153 mutation also led to reduced expression of the tagF1 gene. These results show that Lp_1153 is a regulatory factor that plays a role in WTA alditol switching in Lb. plantarum WCFS1 and we propose to rename this gene/protein wasR/WasR, for WTA alditol switch regulator. PMID- 26678993 TI - Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial. AB - BACKGROUND: Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls. AIM: Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes. METHODS & RESULTS: We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 +/- 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals. CONCLUSION: Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction. PMID- 26678995 TI - Liver transcriptomic networks reveal main biological processes associated with feed efficiency in beef cattle. AB - BACKGROUND: The selection of beef cattle for feed efficiency (FE) traits is very important not only for productive and economic efficiency but also for reduced environmental impact of livestock. Considering that FE is multifactorial and expensive to measure, the aim of this study was to identify biological functions and regulatory genes associated with this phenotype. RESULTS: Eight genes were differentially expressed between high and low feed efficient animals (HFE and LFE, respectively). Co-expression analyses identified 34 gene modules of which 4 were strongly associated with FE traits. They were mainly enriched for inflammatory response or inflammation-related terms. We also identified 463 differentially co-expressed genes which were functionally enriched for immune response and lipid metabolism. A total of 8 key regulators of gene expression profiles affecting FE were found. The LFE animals had higher feed intake and increased subcutaneous and visceral fat deposition. In addition, LFE animals showed higher levels of serum cholesterol and liver injury biomarker GGT. Histopathology of the liver showed higher percentage of periportal inflammation with mononuclear infiltrate. CONCLUSION: Liver transcriptomic network analysis coupled with other results demonstrated that LFE animals present altered lipid metabolism and increased hepatic periportal lesions associated with an inflammatory response composed mainly by mononuclear cells. We are now focusing to identify the causes of increased liver lesions in LFE animals. PMID- 26678994 TI - Lessons from other diseases: granulomatous inflammation in leishmaniasis. AB - The Leishmania granuloma shares some, though not all, properties with that formed following mycobacterial infection. As a simplified, noncaseating granuloma composed of relatively few and largely mononuclear cell populations, it provides a tractable model system to investigate intra-granuloma cellular dynamics, immune regulation, and antimicrobial resistance. Here, the occurrence of granulomatous pathology across the spectrum of leishmaniasis, in humans and animal reservoir hosts, is first described. However, this review focuses on the process of hepatic granuloma formation as studied in rodent models of visceral leishmaniasis, starting from the initial infection of Kupffer cells to the involution of the granuloma after pathogen clearance. It describes how the application of intravital imaging and the use of computational modeling have changed some of our thoughts on granuloma function, and illustrates how host-directed therapies have been used to manipulate granuloma form and function for therapeutic benefit. Where appropriate, lessons that may be equally applicable across the spectrum of granulomatous diseases are highlighted. PMID- 26678997 TI - Factors Impacting Transgender Patients' Discomfort with Their Family Physicians: A Respondent-Driven Sampling Survey. AB - BACKGROUND: Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada. METHODS: 433 trans people age 16 and over were surveyed using respondent driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via average marginal predictions, for transmasculine (n = 184) and transfeminine (n = 172) trans persons. RESULTS: Among the 83.1% (95% CI = 77.4, 88.9) of trans Ontarians who had a family physician, approximately half reported discomfort discussing trans health issues. 37.2% of transmasculine and 38.1% of transfeminine persons reported at least one trans-specific negative experience. In unadjusted analysis, sociodemographics did not predict discomfort, but those who planned to medically transition sex, but had not begun, were more likely to report discomfort (transmasculine: PRR = 2.62 (95% CI = 1.44, 4.77); transfeminine: PRR = 1.85 (95% CI = 1.08, 3.15)). Adjusted for other factors, greater perceived physician knowledge about trans issues was associated with reduced likelihood of discomfort, and previous trans-specific negative experiences with a family physician with increased discomfort. Transfeminine persons who reported three or more types of negative experiences were 2.26 times as likely, and transmasculine persons 1.61 times as likely, to report discomfort. In adjusted analyses, sociodemographic associations differed by gender, with being previously married or having higher education associated with increased risk of discomfort among transfeminine persons, but decreased risk among transmasculine persons. CONCLUSIONS: Within this transgender population, discomfort in discussing trans health issues with a family physician was common, presenting a barrier to accessing primary care despite having a regular family physician and "universal" health insurance. PMID- 26678996 TI - Implementation conditions for diet and physical activity interventions and policies: an umbrella review. AB - BACKGROUND: This umbrella review aimed at identifying evidence-based conditions important for successful implementation of interventions and policies promoting a healthy diet, physical activity (PA), and a reduction in sedentary behaviors (SB). In particular, we examined if the implementation conditions identified were intervention-specific or policy-specific. This study was undertaken as part of the DEterminants of DIet and Physical Activity (DEDIPAC) Knowledge Hub, a joint action as part of the European Joint Programming Initiative a Healthy Diet for a Healthy Life. METHODS: A systematic review of reviews and stakeholder documents was conducted. Data from nine scientific literature databases were analyzed (95 documents met the inclusion criteria). Additionally, published documentation of eight major stakeholders (e.g., World Health Organization) were systematically searched (17 documents met the inclusion criteria). The RE-AIM framework was used to categorize elicited conditions. Across the implementation conditions 25 % were identified in at least four documents and were subsequently classified as having obtained sufficient support. RESULTS: We identified 312 potential conditions relevant for successful implementation; 83 of these received sufficient support. Using the RE-AIM framework eight implementation conditions that obtained support referred to the reach in the target population; five addressed efficacy of implementation processes; 24 concerned adoption by the target staff, setting, or institutions; 43 referred to consistency, costs, and adaptations made in the implementation process; three addressed maintenance of effects over time. The vast majority of implementation conditions (87.9 %; 73 of 83) were supported by documents referring to both interventions and policies. There were seven policy specific implementation conditions, which focused on increasing complexities of coexisting policies/legal instruments and their consequences for implementation, as well as politicians' collaboration in implementation. CONCLUSIONS: The use of the proposed list of 83 conditions for successful implementation may enhance the implementation of interventions and policies which pursue identification of the most successful actions aimed at improving diet, PA and reducing SB. PMID- 26678999 TI - Prophylactic antibiotics in total joint arthroplasty: evolution or devolution? PMID- 26678998 TI - Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. AB - The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection. PMID- 26679001 TI - Design of a novel biomedical signal processing and analysis tool for functional neuroimaging. AB - In this paper, a MATLAB-based graphical user interface (GUI) software tool for general biomedical signal processing and analysis of functional neuroimaging data is introduced. Specifically, electroencephalography (EEG) and electrocardiography (ECG) signals can be processed and analyzed by the developed tool, which incorporates commonly used temporal and frequency analysis methods. In addition to common methods, the tool also provides non-linear chaos analysis with Lyapunov exponents and entropies; multivariate analysis with principal and independent component analyses; and pattern classification with discriminant analysis. This tool can also be utilized for training in biomedical engineering education. This easy-to-use and easy-to-learn, intuitive tool is described in detail in this paper. PMID- 26679004 TI - Extraordinary Strong Fluorescence Evolution in Phosphor on Graphene. AB - Optical transition between singlet and triplet is observed in phosphorescent platinum octaethylporphyrin (PtOEP), on a graphene substrate. PtOEP on single layer of graphene not only modulates the dominant emission wavelength but also enhances the emission intensity. This result addresses new light-matter interactions of the hybrid structure of graphene and a single molecule. PMID- 26679003 TI - A strategy for residual error modeling incorporating scedasticity of variance and distribution shape. AB - Nonlinear mixed effects models parameters are commonly estimated using maximum likelihood. The properties of these estimators depend on the assumption that residual errors are independent and normally distributed with mean zero and correctly defined variance. Violations of this assumption can cause bias in parameter estimates, invalidate the likelihood ratio test and preclude simulation of real-life like data. The choice of error model is mostly done on a case-by case basis from a limited set of commonly used models. In this work, two strategies are proposed to extend and unify residual error modeling: a dynamic transform-both-sides approach combined with a power error model (dTBS) capable of handling skewed and/or heteroscedastic residuals, and a t-distributed residual error model allowing for symmetric heavy tails. Ten published pharmacokinetic and pharmacodynamic models as well as stochastic simulation and estimation were used to evaluate the two approaches. dTBS always led to significant improvements in objective function value, with most examples displaying some degree of right skewness and variances proportional to predictions raised to powers between 0 and 1. The t-distribution led to significant improvement for 5 out of 10 models with degrees of freedom between 3 and 9. Six models were most improved by the t distribution while four models benefited more from dTBS. Changes in other model parameter estimates were observed. In conclusion, the use of dTBS and/or t distribution models provides a flexible and easy-to-use framework capable of characterizing all commonly encountered residual error distributions. PMID- 26679005 TI - Cutaneous adverse reactions of imatinib therapy in patients with chronic myeloid leukemia: A six-year follow up. AB - Imatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Cutaneous adverse reactions of imatinib therapy have been reported in 7%-88.9% patients. We sought to evaluate the prevalence rates of cutaneous adverse reactions of imatinib therapy and to investigate the clinical and pathological characteristics of these reactions. Sixty-six patients (36 men, 30 women; age range 19-83 years) with CML treated with imatinib between 2008 and 2014 were included in the study. Clinical and pathological features of the adverse reactions were investigated. Cutaneous adverse reactions were the most common adverse effects of imatinib therapy and were seen in nine patients with a prevalence rate of 13.6%. The second most common adverse effect was musculoskeletal pain (12.1%). The following cutaneous reactions were observed in patients: edema, rash, pigmentary changes, aphthous stomatitis, alopecia, cutaneous dryness, hyperhidrosis and cheilitis. Imatinib therapy was discontinued in four patients because of various adverse effects. Although the prevalence rate of cutaneous adverse reactions in our study was lower than that in several other studies, cutaneous reactions were common in our study. The relatively low prevalence rate of adverse reactions may be related to the low dosage of imatinib (400 mg/day) used to treat our patients and may have been affected by pharmacogenetic characteristics of our population. PMID- 26679002 TI - LipidII: Just Another Brick in the Wall? AB - Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow. The focus of this review is on exciting new developments, both with respect to antibacterials targeting LipidII as well as the emerging role of LipidII in organizing the membrane and cell wall synthesis. It appears that on both sides of the membrane, LipidII plays crucial roles in organizing cytoskeletal proteins and peptidoglycan synthesis machineries. Finally, the recent discovery of no less than three different categories of LipidII flippases will be discussed. PMID- 26679006 TI - Evaluation of Nursing Documentation Completion of Stroke Patients in the Emergency Department: A Pre-Post Analysis Using Flowsheet Templates and Clinical Decision Support. AB - The primary aim of this performance improvement project was to determine whether the electronic health record implementation of stroke-specific nursing documentation flowsheet templates and clinical decision support alerts improved the nursing documentation of eligible stroke patients in seven stroke-certified emergency departments. Two system enhancements were introduced into the electronic record in an effort to improve nursing documentation: disease-specific documentation flowsheets and clinical decision support alerts. Using a pre-post design, project measures included six stroke management goals as defined by the National Institute of Neurological Disorders and Stroke and three clinical decision support measures based on entry of orders used to trigger documentation reminders for nursing: (1) the National Institutes of Health's Stroke Scale, (2) neurological checks, and (3) dysphagia screening. Data were reviewed 6 months prior (n = 2293) and 6 months following the intervention (n = 2588). Fisher exact test was used for statistical analysis. Statistical significance was found for documentation of five of the six stroke management goals, although effect sizes were small. Customizing flowsheets to meet the needs of nursing workflow showed improvement in the completion of documentation. The effects of the decision support alerts on the completeness of nursing documentation were not statistically significant (likely due to lack of order entry). For example, an order for the National Institutes of Health Stroke Scale was entered only 10.7% of the time, which meant no alert would fire for nursing in the postintervention group. Future work should focus on decision support alerts that trigger reminders for clinicians to place relevant orders for this population. PMID- 26679007 TI - Variable-Temperature Tip-Enhanced Raman Spectroscopy of Single-Molecule Fluctuations and Dynamics. AB - Structure, dynamics, and coupling involving single-molecules determine function in catalytic, electronic or biological systems. While vibrational spectroscopy provides insight into molecular structure, rapid fluctuations blur the molecular trajectory even in single-molecule spectroscopy, analogous to spatial averaging in measuring large ensembles. To gain insight into intramolecular coupling, substrate coupling, and dynamic processes, we use tip-enhanced Raman spectroscopy (TERS) at variable and cryogenic temperatures, to slow and control the motion of a single molecule. We resolve intrinsic line widths of individual normal modes, allowing detailed and quantitative investigation of the vibrational modes. From temperature dependent line narrowing and splitting, we quantify ultrafast vibrational dephasing, intramolecular coupling, and conformational heterogeneity. Through statistical correlation analysis of fluctuations of individual modes, we observe rotational motion and spectral fluctuations of the molecule. This work demonstrates single-molecule vibrational spectroscopy beyond chemical identification, opening the possibility for a complete picture of molecular motion ranging from femtoseconds to minutes. PMID- 26679008 TI - ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics. AB - BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance. PMID- 26679009 TI - Antidepressants and heart-rate variability in older adults: a population-based study. AB - BACKGROUND: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study. METHOD: In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991-2012). Two HRV variables were studied based on 10 s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs. RESULTS: We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes. CONCLUSION: TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors. PMID- 26679010 TI - Influence of inoculum and climatic factors on the severity of Fusarium head blight in German spring and winter barley. AB - Fusarium head blight (FHB) of small cereals is a disease of global importance with regard to economic losses and mycotoxin contamination harmful to human and animal health. In Germany, FHB is predominantly associated with wheat and F. graminearum is recognised as the major causal agent of the disease, but little is known about FHB of barley. Monitoring of the natural occurrence of FHB on Bavarian barley revealed differences for individual Fusarium spp. in incidence and severity of grain infection between years and between spring and winter barley. Parallel measurement of fungal DNA content in grain and mycotoxin content suggested the importance of F. graminearum in winter barley and of F. langsethiae in spring barley for FHB. The infection success of these two species was associated with certain weather conditions and barley flowering time. Inoculation experiments in the field revealed different effects of five Fusarium spp. on symptom formation, grain yield and mycotoxin production. A significant association between fungal infection of grain and mycotoxin content was observed following natural or artificial infection with the type B trichothecene producer F. culmorum, but not with the type A trichothecene-producing species F. langsethiae and F. sporotrichioides. Trichothecene type A toxin contamination also occurred in the absence of significant damage to grain and did not necessarily promote fungal colonisation. PMID- 26679011 TI - Four receptor-like cytoplasmic kinases regulate development and immunity in rice. AB - Receptor-like cytoplasmic kinases (RLCKs) represent a large family of proteins in plants. However, few RLCKs have been well characterized. Here, we report the functional characterization of four rice RLCKs - OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII. These OsRLCKs interact with the rice brassinosteroid receptor, OsBRI1 in yeast cell, but not the XA21 immune receptor. Transgenic lines silenced for each of these genes have enlarged leaf angles and are hypersensitive to brassinolide treatment compared to wild type rice. Transgenic plants silenced for OsRLCK57 had significantly fewer tillers and reduced panicle secondary branching, and lines silenced for OsRLCK107 and OsRLCK118 produce fewer seeds. Silencing of these genes decreased Xa21 gene expression and compromised XA21-mediated immunity to Xanthomonas oryzae pv. oryzae. Our study demonstrates that these OsRLCKs negatively regulate BR signalling, while positively regulating immune responses by contributing to the expression of the immune receptor XA21. PMID- 26679012 TI - Chronic Abdominal Pain from Inferior Vena Cava Filter Strut Perforation: A Case Report. PMID- 26679014 TI - Changing minds about tuberculosis. PMID- 26679013 TI - Asymmetric Modulation of Protein Order-Disorder Transitions by Phosphorylation and Partner Binding. AB - As for many intrinsically disordered proteins, order-disorder transitions in the N-terminal oligomerization domain of the multifunctional nucleolar protein nucleophosmin (Npm-N) are central to its function, with phosphorylation and partner binding acting as regulatory switches. However, the mechanism of this transition and its regulation remain poorly understood. In this study, single molecule and ensemble experiments revealed pathways with alternative sequences of folding and assembly steps for Npm-N. Pathways could be switched by altering the ionic strength. Phosphorylation resulted in pathway-specific effects, and decoupled folding and assembly steps to facilitate disorder. Conversely, binding to a physiological partner locked Npm-N in ordered pentamers and counteracted the effects of phosphorylation. The mechanistic plasticity found in the Npm-N order disorder transition enabled a complex interplay of phosphorylation and partner binding steps to modulate its folding landscape. PMID- 26679015 TI - International donor conversion rates for lung transplantation need to be standardised. PMID- 26679016 TI - ARDS in 2015: new clinical directions, new biological insights. PMID- 26679017 TI - Asthma: a focus on four key areas in 2015. PMID- 26679018 TI - Bronchiectasis: working together for better evidence. PMID- 26679019 TI - The complex challenge of chronic obstructive pulmonary disease. PMID- 26679020 TI - Lessons for pulmonary critical care from treatment of Ebola virus disease in developed countries. PMID- 26679021 TI - Idiopathic pulmonary fibrosis: continuing to make progress. PMID- 26679022 TI - Immunotherapy: the third wave in lung cancer treatment. PMID- 26679023 TI - Lung health care-what does the future have in store? PMID- 26679024 TI - Getting the story. PMID- 26679025 TI - Cardiovascular and neuropsychiatric risks of varenicline: too good to be true? PMID- 26679026 TI - Cardiovascular and neuropsychiatric risks of varenicline: too good to be true? PMID- 26679027 TI - Cardiovascular and neuropsychiatric risks of varenicline: too good to be true? PMID- 26679029 TI - Use of FEV1 as a measure of lung health in the UK BiLEVE study. PMID- 26679028 TI - Cardiovascular and neuropsychiatric risks of varenicline: too good to be true? - Authors' reply. PMID- 26679030 TI - Use of FEV1 as a measure of lung health in the UK BiLEVE study - Authors' reply. PMID- 26679032 TI - Corrections. PMID- 26679031 TI - Hyperinflation in COPD exacerbations. PMID- 26679033 TI - Corrections. PMID- 26679034 TI - Corrections. PMID- 26679036 TI - Benzimidazole-Branched Isomeric Dyes: Effect of Molecular Constitution on Photophysical, Electrochemical, and Photovoltaic Properties. AB - Three benzimidazole-based isomeric organic dyes possessing two triphenylamine donors and a cyanoacrylic acid acceptor are prepared by stoichiometrically controlled Stille or Suzuki-Miyaura coupling reaction which predominantly occurs on the N-butyl side of benzimidazole due to electronic preferences. Combined with the steric effect of the N-butyl substituent, placement of the acceptor segment at various nuclear positions of benzimidazole such as C2, C4, and C7 led to remarkable variations in intramolecular charge transfer absorption, electron injection efficiency, and charge recombination kinetics. The substitution of acceptor on the C4 led to red-shifted absorption, while that on C7 retarded the charge transfer due to twisting in the structure caused by the butyl group. Because of the cross-conjugation nature and poor electronic interaction between the donor and acceptor, the dye containing triphenylamine units on C4 and C7 and the acceptor unit on C2 showed the low oxidation potential. Thus, this dye possesses favorable HOMO and LUMO energy levels to render efficient sensitizing action in solar cells. Consequently, it results in high power conversion efficiency (5.01%) in the series with high photocurrent density and open circuit voltage. The high photocurrent generation by this dye is reasoned to it exceptional charge collection efficiency as determined from the electron impedance spectroscopy. PMID- 26679037 TI - Global measures of peripheral blood-derived DNA methylation as a risk factor in the development of mature B-cell neoplasms. AB - AIM: To examine whether peripheral blood methylation is associated with risk of developing mature B-cell neoplasms (MBCNs). MATERIALS & METHODS: We conducted a case-control study nested within a large prospective cohort. Peripheral blood was collected from healthy participants. Cases of MBCN were identified by linkage to cancer registries. Methylation was measured using the Infinium((r)) HumanMethylation450. RESULTS: During a median of 10.6-year follow-up, 438 MBCN cases were evaluated. Global hypomethylation was associated with increased risk of MBCN (odds ratio: 2.27, [95% CI: 1.59-3.25]). Within high CpG promoter regions, hypermethylation was associated with increased risk (odds ratio: 1.76 [95% CI: 1.25-2.48]). Promoter hypermethylation was observed in HOXA9 and CDH1 genes. CONCLUSION: Aberrant global DNA methylation is detectable in peripheral blood collected years before diagnosis and is associated with increased risk of MBCN, suggesting changes to DNA methylation are an early event in MBCN development. PMID- 26679038 TI - Effects of Ligand Geometry on the Photophysical Properties of Photoluminescent Eu(III) and Sm(III) 1-Hydroxypyridin-2-one Complexes in Aqueous Solution. AB - A series of 10 tetradentate 1-hydroxy-pyridin-2-one (1,2-HOPO) ligands and corresponding eight-coordinated photoluminescent Eu(III) and Sm(III) complexes were prepared. Generally, the ligands differ by the linear (nLI) aliphatic linker length, from 2 to 8 methylene units between the bidentate 1,2-HOPO chelator units. The photoluminescent quantum yields (Phitot) were found to vary with the linker length, and the same trend was observed for the Eu(III) and Sm(III) complexes. The 2LI and 5LI bridged complexes are the brightest (Phitotxepsilon). The change in ligand wrapping pattern between 2LI and 5LI complexes observed by X ray diffraction (XRD) is further supported by density functional theory (DFT) calculations. The bimodal Phitot trends of the Eu(III) and Sm(III) complexes are rationalized by the change in ligand wrapping pattern as the bridge (nLI) is increased in length. PMID- 26679039 TI - The complete mitochondrial genome of a spiraling whitefly, Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae). AB - We report the complete mitochondrial genome (mitogenome) of a spiraling whitefly, Aleurodicus dispersus (Hemiptera: Aleyrodidae). The 16 170 bp long genome consists of 13 protein-coding genes, 20 transfer RNAs, 2 ribosomal RNAs, and a control region. The A. dispersus mitogenome also includes a cytb-like non-coding region and shows several variations relative to the typical insect mitogenome. A phylogenetic tree has been constructed using the 13 protein-coding genes of 12 related species from Hemiptera. Our results would contribute to further study of phylogeny in Aleyrodidae and Hemiptera. PMID- 26679040 TI - Current response of a topological insulator to a static Zeeman field. AB - We study the magnetoelectric coupling at the surface of a topological insulator. We are particularly interested in the surface current induced by a static Zeeman/exchange field. This surface current can be related to the orbital magnetization of the system. For an insulator with zero Chern number, the orbital magnetization is independent of the details at the boundary. With the appearance of surface states in the topological insulator, it is not immediately obvious if the response is affected by the conditions at the surface. We investigate this question using exact diagonalization to a lattice model. By applying a time reversal symmetry-breaking term near the boundary, even if the surface states are gapped out, we still find no change in the surface current. This arises from cancelations between Pauli and Van Vleck contributions between surface and bulk scattering states. We also show that the surface current response is independent of the chemical potential when it is within the bulk gap. Our results are consistent with the claim that orbital magnetization is a bulk property. PMID- 26679041 TI - Microbiome and Beyond: Non-Viable Food Microbes and Human Health. PMID- 26679042 TI - Implementation of hospital-wide reform at improving access and flow: Impact on time to antibiotics in the emergency department. AB - INTRODUCTION: ED overcrowding has been associated with increased mortality, morbidity and delays to essential treatment. It was hypothesised that hospital wide reforms designed to improve patient access and flow, in addition to improving ED overcrowding, would impact on clinically important processes within the ED, such as timely delivery of antibiotics. METHODS: A single pre implementation and post-implementation prospective cohort study was conducted prior to and after a hospital-wide reform (Timely Quality Care (TQC)). Among patients who had intravenous antibiotics prescribed in the ED, data were prospectively collected on times of presentation, prescription and administration of antibiotics. Demographics and discharge diagnoses were retrospectively extracted. RESULTS: There were 380 cases included with 179 cases prior to introduction of the TQC model and 201 cases after its introduction. Time from presentation to administration of antibiotics improved significantly from 192 (99 320) min to 142 (81-209) min (P < 0.01). The time from presentation to prescription pre-TQC and post-TQC was 120 (51-230) min and 92 (49-153) min, respectively (P < 0.01). The times from prescription to administration pre-TQC and post-TQC were 43 (20-83) min and 34 (15-66) min, respectively (P = 0.03). CONCLUSION: Following implementation of hospital-wide reform directed at mitigating ED overcrowding through improved access and flow, times to administration of antibiotics were significantly reduced. These findings suggest that improved quality of care in this area may be achieved with processes aimed at improved hospital access and flow. Ongoing evaluation and vigilance is necessary to ensure sustainability and drive further improvements. PMID- 26679043 TI - Discrete structural features among interface residue-level classes. AB - BACKGROUND: Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. RESULTS: Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. CONCLUSIONS: Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs. PMID- 26679044 TI - How 'ground-picked' olive fruits affect virgin olive oil ethanol content, ethyl esters and quality. AB - BACKGROUND: Olives dropped on the ground naturally sometimes are not separated from those fresh and healthy collected from the tree for harvest and processing. In this work we compared the quality, ethanol content and bioactive components of virgin olive oils from ground-picked olives, tree-picked fruits and their mixture. RESULTS: Ground-picked olives produced 'Lampante' virgin olive oils; these are of a lower quality category, because of important alterations in chemical and sensory characteristics. Ethyl esters showed the highest values, although under the regulated limit. The mixture of ground and tree-picked olives gave oils classified as 'virgin' because of sensory defects, although the quality parameters did not exceed the limits for the 'extra' category. Ethanol content showed a significant increase in the oils from ground- picked olives and their mixture with respect to those from tree-picked fruits. Furthermore, bioactive compounds showed a significant decrease as fruit quality was poorer. CONCLUSION: Ground-picked olives must be harvested and processed separately since they produce low-quality virgin olive oils with sensory defects and lower concentrations of bioactive compounds. The higher acidity and ethanol concentration observed in oils from ground-picked fruits or their mixture may help ethyl ester synthesis during storage. (c) 2015 Society of Chemical Industry. PMID- 26679045 TI - Relaying the Ethylene Signal: New Roles for EIN2. AB - ETHYLENE INSENSITIVE 2 (EIN2), an endoplasmic reticulum (ER) localized protein, plays a central role in relaying the ethylene signal from ER perception to the nucleus. Two recent reports reveal the novel role for EIN2 in translational control, providing another layer of regulation for ethylene signal transduction. PMID- 26679046 TI - Improved biogas production from food waste by co-digestion with de-oiled grease trap waste. AB - The objective of this study was to assess the feasibility of co-digesting food waste (FW) and de-oiled grease trap waste (GTW) to improve the biogas production. A lab-scale mesophilic digester (MD), a temperature-phased anaerobic digester (TPAD) and a TPAD with recycling (TPAD-R) were synchronously operated under mono digestion (FW) and co-digestion (FW+de-oiled GTW). Co-digestion increased the biogas yield by 19% in the MD and TPAD-R, with a biogas yield of 0.60L/g VS added. Specific methanogenic activity in the TPAD-R was much higher than that in the MD. In addition to methane, hydrogen at a yield of approximately 1mol/mol hexose was produced in the TPAD-R. Alkalinity was consumed more in the co digestion than in mono-digestion. Co-digestion resulted in more lipid accumulation in each digester. The MD favored the degradation of lipid and conversion of long-chain fatty acids more than the TPAD and TPAD-R. PMID- 26679047 TI - Thermodynamic analysis of effects of contact angle on interfacial interactions and its implications for membrane fouling control. AB - Concept of hydrophobicity always fails to accurately assess the interfacial interaction and membrane fouling, which calls for reliable parameters for this purpose. In this study, effects of contact angle on interfacial interactions related to membrane fouling were investigated based on thermodynamic analysis. It was found that, total interaction energy between sludge foulants and membrane monotonically decreases and increases with water and glycerol contact angle, respectively, indicating that these two parameters can be reliable indicators predicting total interaction energy and membrane fouling. Membrane roughness decreases interaction strength for over 20 times, and effects of membrane roughness on membrane fouling should consider water and glycerol contact angle on membrane. It was revealed existence of a critical water and glycerol contact angle for a given membrane bioreactor. Meanwhile, diiodomethane contact angle has minor effect on the total interaction, and cannot be regarded as an effective indicator assessing interfacial interactions and membrane fouling. PMID- 26679048 TI - Biodegradation of 3,3',4,4'-tetrachlorobiphenyl by Sinorhizobium meliloti NM. AB - A rhizobial strain, Sinorhizobium meliloti NM, could use 3,3',4,4'-tetrachloro biphenyl (PCB 77) as the sole carbon and energy source for growth in mineral salt medium. The degradation efficiency of PCB 77 by strain NM and the bacterial growth increased with a decrease in PCB 77 concentration (5-0.25mgL(-1)). The addition of secondary carbon sources, phenolic acids and one surfactant influenced PCB 77 degradation, rhizobial growth and biofilm formation. The highest degradation efficiency was observed in the presence of caffeic acid. Benzoate and chloride ions were detected as the PCB 77 metabolites. The up regulation of benzoate metabolism-related gene expression was also observed using quantitative reverse transcription-polymerase chain reaction. This report is the first to demonstrate Sinorhizobium using coplanar tetrachlorobiphenyl as a sole carbon and energy source, indicating the potential wide benefit to the field of rhizobia-assisted bioremediation. PMID- 26679049 TI - Thermophilic Geobacillus galactosidasius sp. nov. loaded gamma-Fe2O3 magnetic nanoparticle for the preconcentrations of Pb and Cd. AB - Thermophilic bacteria, Geobacillus galactosidasius sp nov. was loaded on gamma Fe2O3 magnetic nanoparticle for the preconcentrations of Pb and Cd by solid phase extraction before ICP-OES. pH and flow rate of the solution, amounts of biosorbent and magnetic nanoparticle, volume of sample solution, effects of the possible interferic ions were investigated in details. Linear calibration curves were constructed in the concentration ranges of 1.0-60ngmL(-1) for Pb and Cd. The RSDs of the method were lower than 2.8% for Pb and 3.8% for Cd. Certified and standard reference samples of fortified water, wastewater, poplar leaves, and simulated fresh water were used to accurate the method. LOD values were found as 0.07 and 0.06ngmL(-1) respectively for Pb and Cd. The biosorption capacities were found as 34.3mgg(-1) for Pb and 37.1mgg(-1) for Cd. Pb and Cd concentrations in foods were determined. Surface microstructure was investigated by SEM-EDX. PMID- 26679050 TI - Biomass and lipid enhancement in Chlorella sp. with emphasis on biodiesel quality assessment through detailed FAME signature. AB - In this study, the concentrations of MgSO4, salinity and light intensity were optimised for maximum biomass productivity and lipid content in Chlorella sp. Lipid synthesized at varied experimental conditions was also assessed in detail for biodiesel properties through FAME analysis. FAMEs mainly composed of C16:0, C16:1(9), C16:3(7, 10, 13), C18:0, C18:1(11), C18:2(9, 12), C18:3(9, 12, 15). The optimum biomass productivity (372.50mgL(-1)d(-1)) and lipid content (32.57%) was obtained at MgSO4-150ppm; salinity-12.5ppm, and light intensity-25MUmolm(-2)s( 1). However, at this condition the cetane number, a major biodiesel property was not complying with worldwide biodiesel standard. Therefore, further optimisations were done to check the suitability of biodiesel fuel. The optimum biomass productivity (348.47mgL(-1)d(-1)) and lipid content (12.43%) with suitable biodiesel fuel properties was obtained at MgSO4-50ppm, salinity-25ppm and light intensity-100MUmolm(-2)s(-1). The validation experiments confirmed the closeness of predicted and measured response values. PMID- 26679051 TI - A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy. AB - Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC 43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC 43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC. PMID- 26679052 TI - Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms. AB - Bladder cancer is the ninth most common cancer around the world, and is a severe urological cancer irrespective of sex. Approximately 65% of the bladder cancers will recur following surgery; with more than 20% of those patients showing an advanced and metastatic stage, with reducing prognosis. Metastasis causes the most death of bladder cancer yet current therapeutic options remain limited. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, has been identified as a strong cytotoxic agent against lung and metastatic breast cancer cells; however, the effects and mechanisms of antrocin on cancer growth and metastasis remain largely unclear. This study showed that treatment with cytotoxic concentration of antrocin induced both intrinsic and extrinsic apoptotic pathways in human bladder cancer 5637 cells, evidenced by increase of Fas, DR5, Bax expression and caspase-3, -8 and -9 activation. Exposure to non cytotoxic concentrations of antrocin significantly inhibited cell growth, migration, and invasion, which was associated with decreased phosphorylation of focal adhesion kinase (FAK) and paxillin. Antrocin also reduced subcellular distribution of FAK and paxillin at the focal adhesion contacts of the cell periphery site, and disrupted the formation of filopodia and lamellipodia. Moreover, antrocin increased epithelial-to-mesenchymal transition-related gene E cadherin and decreased vimentin expression. Real-time PCR analysis showed that antrocin downregulated the expression of mRNA of several MMPs, including MMP-2. Moreover, the phosphorylation of ERK and c-Fos were also attenuated by antrocin. Data from chromatin immunoprecipitation assay demonstrated that antrocin decreased the DNA binding activity of c-Fos to the upstream/enhancer region of MMP-2 promoter, an action likely to result in the reducing MMP-2 expression. Overall, this is the first study which demonstrates that antrocin-inhibited migration and invasion of bladder cancer cells is partly via inactivation of FAK paxillin and ERK-c-Fos-MMP2 signaling pathways. Both antrocin-induced intrinsic and extrinsic apoptosis is through upregulation of pro-apoptotic proteins, including Bax, Fas, and DR5. These results provide insights for understanding the anti-cancer effects and mechanisms of antrocin in human bladder cancer cells and indicate that antrocin may be a potential therapeutic agent for invasive bladder cancer cells by inhibition of metastasis and induction of apoptosis. PMID- 26679053 TI - Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells. AB - Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem like state in spheroids, we transferred TIC-enriched spheroid cultures to serum containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth. PMID- 26679054 TI - Synthesis and photophysical studies of tetrazolate-based Eu(III) photoluminescent ternary complexes containing N-heterocyclic phosphine oxides auxiliary co ligands. AB - Two new ternary tetrazolate Eu(III) complexes with phosphine oxide co-ligands Eu(PTO)3 .(P1/P2) [PTO = 5-(2-pyridyl-1-oxide)tetrazole, P1 = diphenylphosphorylamino-phenylphosphoryl-benzene, P2 = diphenylphosphorylpyridine)-bis-isobutyricphosphoryl] were synthesized and characterized using UV, fluorescence, IR and (1) H NMR spectroscopic techniques. The analytical data prove that the complexes are mononuclear in nature and the central Eu(III) ion is coordinated by three N and three O atoms of tetrazolate, and two O atoms of the corresponding bidentate phosphine oxide ligands. The ancillary ligand increased the photoluminescence efficiency of Eu(PTO)3 .P1 (complex 3) by twofold compared with our previously reported Eu(PTO)3 complex (complex 1). Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26679055 TI - Effects of a training in the Disability Assessment Structured Interview on the interviews of Dutch insurance physicians. AB - PURPOSE: The Disability Assessment Structured Interview (DASI) is a semi structured interview for assessing functional limitations of claimants in a work disability evaluation. The aim of this study is to evaluate the effect of a 3-day DASI training course on the quality of assessment interviews of insurance physicians (IPs). METHODS: In a pretest-posttest study, 55 IPs employed at the Dutch National Institute for Employee Benefits Schemes completed a 3-day DASI training. Before (T0), directly after the training (T1) and after 3 months follow up (T2), these IPs filled out questionnaires that measured knowledge, skills, attitude and self-efficacy. Furthermore, in 10 disability assessment cases interview duration, IP's satisfaction, amount of acquired information and confidence of judgement were measured. Finally, the amount of information reported was measured in three randomly selected disability assessment reports of each IP. RESULTS: IP's knowledge, skills and self-efficacy improved significantly after the training. The attitude of the IPs changed towards a more open attitude and structuring of the interview. Satisfaction about the interview, amount of acquired information and confidence of their judgement all increased. CONCLUSIONS: The DASI training improved the quality of assessment interviews of IPs. A semi-structured interview, like the DASI, can help physicians to pay more attention to activity limitations and participation in addition to medical information. Implications for Rehabilitation Experienced IPs are able to change their disability assessment interview routine after training. In determining work ability, IPs should pay more attention to claimant's activity limitations and participation in addition to medical information. A semi-structured interview as the DASI can help IPs to pay more attention to claimant's functioning. A 3-day DASI training for IPs can increase their confidence in their judgement and provides significantly more information in their assessment reports. PMID- 26679057 TI - Palbociclib for the treatment of postmenopausal breast cancer - an update. AB - INTRODUCTION: Breast cancer is a heterogeneous disease comprising different biological subtypes. In two thirds of tumours, expression of steroid-receptors is present, allowing for targeted treatment with endocrine therapy. In metastatic breast cancer, sequential administration of different non-cross resistant drugs offers a chance to delay cytotoxic chemotherapy. Activity of endocrine therapy, however, decreases with time as indicated by a shorter progression-free survival interval with every further treatment line, suggesting onset of resistance. Current research therefore focuses on prevention or delay of resistance by combining endocrine therapy with other targeted treatment approaches such as small-molecule pathway-inhibitors. Indeed, combining the steroidal aromatase inhibitor exemestane with the mTor-inhibitor everolimus doubles activity of endocrine therapy in a pretreated population albeit at the price of increased toxicity. Data from several clinical trials suggest that inhibitors of the cycline-dependent kinases (CDK) 4 and 6 are able to delay or reverse resistance to endocrine therapy as well, while tolerability may be superior. AREAS COVERED: This review provides a summary of clinical data on CDK 4/6 inhibitors, summarizes the biological rational for their use and provides an outlook to future developments in this field. A systematic literature search was performed in order to identify publications concerning the use of CDK 4/6 inhibitors in breast cancer. The search included original research articles, abstracts from major conferences and reviews published from 2005 to 2015 and was limited to English language publications. EXPERT OPINION: Based upon available data regarding activity and tolerability, it is believed that CDK 4/6 inhibitors will evolve to become a valuable addition to the therapeutic options in metastatic breast cancer. PMID- 26679056 TI - Green tea extract provides extensive Nrf2-independent protection against lipid accumulation and NFkappaB pro- inflammatory responses during nonalcoholic steatohepatitis in mice fed a high-fat diet. AB - SCOPE: Green tea extract (GTE) reduces liver steatosis and inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized GTE would mitigate NASH in a nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent manner in a high fat (HF) induced model. METHODS AND RESULTS: Nrf2-null and wild-type (WT) mice were fed an HF diet containing 0 or 2% GTE for eight weeks prior to assessing parameters of NASH. Compared to WT mice, Nrf2-null mice had increased serum alanine aminotransferase, hepatic triglyceride, expression of free fatty acid uptake and lipogenic genes, malondialdehyde and NFkappaB phosphorylation and expression of pro-inflammatory genes. In WT mice, GTE increased Nrf2 and NADPH:quinone oxidoreductase-1 mRNA, and lowered hepatic steatosis, lipid uptake and lipogenic gene expression, malondialdehyde, and NFkappaB-dependent inflammation. In Nrf2-null mice, GTE lowered NFkappaB phosphorylation and TNF alpha and MCP1 mRNA to levels observed in WT mice fed GTE whereas hepatic triglyceride and lipogenic genes were lowered only to those of WT mice fed no GTE. Malondialdehyde was lowered in Nrf2-null mice fed GTE, but not to levels of WT mice, and without improving the hepatic antioxidants alpha-tocopherol, ascorbic acid and uric acid. CONCLUSION: Nrf2 deficiency exacerbates NASH whereas anti-inflammatory and hypolipidemic activities of GTE likely occur largely independent of Nrf2 signaling. PMID- 26679058 TI - Changes in tibiofemoral contact forces during running in response to in-field gait retraining. AB - We evaluated the efficacy of an in-field gait retraining programme using mobile biofeedback to reduce cumulative and peak tibiofemoral loads during running. Thirty runners were randomised to either a retraining group or control group. Retrainers were asked to increase their step rate by 7.5% over preferred in response to real-time feedback provided by a wrist mounted running computer for 8 routine in-field runs. An inverse dynamics driven musculoskeletal model estimated total and medial tibiofemoral joint compartment contact forces. Peak and impulse per step total tibiofemoral contact forces were immediately reduced by 7.6% and 10.6%, respectively (P < 0.001). Similarly, medial tibiofemoral compartment peak and impulse per step tibiofemoral contact forces were reduced by 8.2% and 10.6%, respectively (P < 0.001). Interestingly, no changes were found in knee adduction moment measures. Post gait retraining, reductions in medial tibiofemoral compartment peak and impulse per step tibiofemoral contact force were still present (P < 0.01). At the 1-month post-retraining follow-up, these reductions remained (P < 0.05). With these per stance reductions in tibiofemoral contact forces in mind, cumulative tibiofemoral contact forces did not change due to the estimated increase in number of steps to run 1 km. PMID- 26679059 TI - Cocaine abuse and effects in the serum levels of cytokines IL-6 and IL-10. AB - BACKGROUND: Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample. METHODS: This is a case-control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. RESULTS: There was a statistically significant increase in IL-6 (p=0.037) and decrease in IL-10 (p=0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p=0.013) among cocaine users individuals, when compared to the control group. CONCLUSIONS: Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments. PMID- 26679061 TI - Letter to the editor: lifestyle medicine in Expert Review of Cardiovascular Therapy. PMID- 26679060 TI - Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence. AB - BACKGROUND: Addiction is associated with dorso-lateral prefrontal cortex (DLPFC) dysfunction and altered brain-oscillations. High frequency repetitive transcranial magnetic stimulation (HFrTMS) over DLPFC reportedly reduces drug craving. Its effects on neuropsychological, behavioural and neurophysiological are unclear. METHODS: We assessed psychological, behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification. Participants were randomized to active HFrTMS (10 Hz, 100% motor threshold) or sham. Immediately before the first and after the last session, 32 channels EEG was recorded and alcohol craving Visual Analogue Scale, Symptom Check List-90-R, Numeric Stroop task and Go/No-go task administered. Tests were repeated at 1-month follow-up. RESULTS: 17 subjects (mean age 44.7 years, 4 F) were assessed. Active rTMS subjects performed better at Stroop test at end of treatment (p=0.036) and follow up (p=0.004) and at Go-NoGo at end of treatment (p=0.05) and follow up (p=0.015). Depressive symptoms decreased at end of active treatment (p=0.036). Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham (p=0.026). No significant modifications over time or group emerged for craving and number of drinks at follow up. CONCLUSION: 4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms. An overall reduction of faster EEG frequencies was observed. Nonetheless, this schedule is ineffective in reducing craving and alcohol intake. PMID- 26679062 TI - VISUAL RECOVERY AFTER AUTOLOGOUS RETINAL PIGMENT EPITHELIUM AND CHOROIDAL PATCH IN A PATIENT WITH CHOROIDAL NEOVASCULARIZATION SECONDARY TO ANGIOID STREAKS: LONG TERM RESULTS. AB - PURPOSE: To describe a successfully treated case of autologous retinal pigment epithelium and choroidal patch in a patient with choroidal neovascularization secondary to angioid streaks. METHODS: A 53-year-old man with angioid streaks and a subfoveal choroidal neovascularization underwent autologous retinal pigment epithelium and choroid transplantation. Lensectomy, pars plana vitrectomy, 200 degrees peripheral temporal retinotomy, isolation of the patch, endolaser, and silicone oil tamponade 1,000 cts were performed. Preoperative and postoperative ophthalmic examinations included best-corrected visual acuity, fluorescein angiography, indocyanine green angiography, autofluorescence, and optical coherence tomography. RESULTS: Two months after surgery, best-corrected visual acuity (Snellen equivalent) improved from 20/200 to 20/100. At 6 months, best corrected visual acuity further increased to 20/40 and the reading ability, which was absent preoperatively, improved to J2. Visual results were maintained after 2.5 years and no recurrence of choroidal neovascularization was observed. CONCLUSION: Transplantation of a full-thickness patch of retinal pigment epithelium and choroid under the fovea may be considered to prevent retinal atrophy with significant visual improvement in the case of a low active choroidal neovascularization secondary to angioid streaks. Moreover, preoperative optical coherence tomography might guide in highlighting those patients in whom the outer retinal layers are still visible as the best candidate for surgery. PMID- 26679063 TI - De novo assembly and characterization of root transcriptome in two distinct morphotypes of vetiver, Chrysopogon zizaniodes (L.) Roberty. AB - Vetiver, a perennial C4 grass, has long been known for its multifarious uses in perfumery, medicine and environmental protection. Two distinct vetiver morphotypes have been identified in India, i.e., A. North Indian type characterized by thick and smooth fast growing roots that produce superior quality of laevorotatory oil; and B. South Indian type with more number of thin and hairy roots that produce inferior quality of dextrorotatory oil. The two morphotypes were targeted for transcriptome analysis to understand the contribution of genetic background on oil quality and root morphology. Sample A showed enhanced activity of flavonoid and terpenoid biosynthesis related genes, i.e. ERF, MYB, bHLH, bZIP and WRKY. Interestingly, expression analysis revealed that the genes involved in sesquiterpene biosynthesis pathway were up regulated in Sample A. Moreover, some of the genes involved in mevalonate pathway of sesquiterpene biosynthesis were unique to Sample A. Our results also demonstrated several transcripts involved in root development and hormonal regulation being up regulated in Sample A. To validate gene expression results of RNA-seq data, 20 transcripts were validated by qRT-PCR experiment. The present study provided an important start point for further discovery of genes related to root oil quality in different ecotypes of vetiver. PMID- 26679064 TI - HIV-related stigma and health-related quality of life among children living with HIV in Sweden. AB - The relationship between HIV-related stigma and health-related quality of life (HRQoL) among children living with HIV infection is unknown. The objectives of this study were to describe HIV-related stigma and HRQoL among children with perinatal HIV living in Sweden, and to investigate the relationship between these two factors in the same infection group. In a cross-sectional nationwide survey, HIV-related stigma was measured with the 8-item HIV Stigma Scale for Children. HRQoL was measured with the 37-item DISABKIDS Chronic Generic Module. Structural equation modeling was used to explore the relationship between HIV-related stigma and HRQoL. Fifty-eight children participated, age 9-18 years (mean = 13.9). The HIV stigma general scale showed a mean score of 17.6 (SD = 5.0; possible range 8 32). DISABKIDS Chronic Generic Module general scale showed a mean score of 80.7 (SD = 14.1; possible range 0-100). HIV-related stigma was negatively associated with HRQoL (standardized beta = -0.790, p = .017). The results indicate that children's concerns related to disclosure of their HIV infection seem to be common (i.e. 75% agreed) which, together with the negative association between ratings of HIV-relatively stigma and HRQoL, might indicate that disclosure concerns would be a relevant target for interventions to decrease HIV-related stigma and increase HRQoL. PMID- 26679065 TI - Association of daylight saving time transitions with incidence and in-hospital mortality of myocardial infarction in Finland. AB - INTRODUCTION: Circadian rhythm disturbance increases cardiovascular risk but the effects of daylight saving time (DST) transitions on the risk of myocardial infarction (MI) are unclear. METHODS: We studied association of DST transitions in 2001-2009 with incidence and in-hospital mortality of MI admissions nationwide in Finland. Incidence rations (IR) of observed incidences on seven days following DST transition were compared to expected incidences. RESULTS: Incidence of MI increased on Wednesday (IR 1.16; CI 1.01-1.34) after spring transition (6298 patients' cohort). After autumn transition (8161 patients' cohort), MI incidence decreased on Monday (IR 0.85; CI 0.74-0.97) but increased on Thursday (IR 1.15; CI 1.02-1.30). The overall incidence of MI during the week after each DST transition did not differ from control weeks. Patient age or gender, type of MI or in-hospital mortality were not associated with transitions. Renal insufficiency was more common among MI patients after spring transition (OR 1.81; CI 1.06-3.09; p < 0.05). Diabetes was less common after spring transition (OR 0.71; CI 0.55-0.91; p = 0.007), but more common after autumn transition (OR 1.21; 1.00-1.46; p < 0.05). CONCLUSIONS: DST transitions are followed by changes in the temporal pattern but not the overall rate of MI incidence. Comorbidities may modulate the effects DST transitions. PMID- 26679066 TI - Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta. AB - Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (MUCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. (c) 2015 American Society for Bone and Mineral Research. PMID- 26679067 TI - Prenatal diagnosis of Nager syndrome in a 12-week-old fetus with a whole gene deletion of SF3B4 by chromosomal microarray. AB - Less than one hundred cases of the acrofacial dysostosis, Nager syndrome, have been described. The cardinal features of Nager syndrome are micrognathia, midface retrusion and limb malformations, predominately of the radial ray of upper extremities. Within the past three years haploinsufficiency of SF3B4 has been confirmed as the major cause of Nager syndrome. Different loss-of-function point mutations in SF3B4 have been found in approximately 2/3 of patients diagnosed with Nager syndrome. Whole gene deletions of SF3B4 have also been suggested to be the cause of Nager syndrome in SF3B4 point mutation negative patients. Only four prenatal cases displaying Nager-like features in the 2nd or 3rd trimester which have been genetically confirmed with SF3B4 point-mutation after birth have been described. We report a case of a 12-week-old fetus with micrognathia, malformed wrists, bilateral club foot and short long bones diagnosed prenatally by chromosomal microarray with a de novo 0.4 Mb deletion at chromosome 1q21.2 involving SF3B4. To our knowledge, this is the first report of Nager syndrome caused by a SF3B4 whole gene deletion. The case presented also shows that high resolution chromosomal microarray in early pregnancy can confirm Nager syndrome caused by SF3B4-deletion prenatally. PMID- 26679068 TI - Congenital Spinal Malformation and Stroke: Aneurysmal Dilatations and Bilateral Rotational Vertebral Artery Occlusion. AB - A 30-year-old woman suffered from acute vertebrobasilar stroke. Cranial tomography (CT) scans showed multiple vertebral abnormalities suggestive of congenital spine malformation, and angiographic CT revealed aneurysmal dilatations (ADs) at segment V2 of both vertebral arteries (VAs). Dynamic neuroimaging tests including angiography and angio-CT were performed and showed occlusion of both VAs at the point of the ADs with contralateral rotation of the neck. The presence of a bony structure causing the artery compression was excluded and embolic phenomena originating at the AD was proposed as the likely source of stroke. Even if infrequent, the presence of craniocervical anomalies should be considered in vertebrobasilar stroke of indeterminate etiology. PMID- 26679069 TI - Routine 24-Hour Computed Tomography Brain Scan is not useful in stable patients Post Intravenous Tissue Plasminogen Activator. AB - BACKGROUND: Obtaining a routine computed tomography (CT) brain scan 24 hours after treatment with intravenous tissue plasminogen activator (IV-tPA) is included in the American Heart Association/American Stroke Association acute stroke guidelines. The usefulness of the test in stable patients is not known. We hypothesized that the results of routine, 24-hour post-treatment neuroimaging (CT or magnetic resonance imaging [MRI] brain scans) would not alter the management of clinically stable patients. METHODS: Patients treated with IV-tPA between January 2011 and December 2013 were identified from a single hospital's stroke registry. All patients were closely monitored for changes in stroke severity. Demographics, changes in neurological status, neuroimaging results, and changes in therapy were abstracted from the patients' medical records. Patients having a neuroimaging study because of neurological deterioration were excluded. RESULTS: Of 136 patients treated with IV-tPA, 131 met criteria for inclusion. Of these, 86.7% had moderate to severe neurological deficits (i.e., initial National Institutes of Health Stroke Scale score > 5 points; median 8 points). All patients had routine imaging ~24 hours after treatment (CT brain 62.6%, MRI brain 12.4%, both CT and MRI brain 25%). Asymptomatic hemorrhagic transformation occurred in 6.7% and potentially changed management in a single patient (target systolic blood pressure was lowered from 185 to 180 mmHg). CONCLUSIONS: Over a 3 year period, routine neuroimaging ~24-hours after IV-tPA in clinically stable patients was associated with a change in therapy in only 1 (.95%) patient. If confirmed in other cohorts, these results suggest that routine neuroimaging after IV-tPA may be safely avoided in clinically stable patients, eliminating unnecessary radiation exposure in those having CT brain and reducing costs. PMID- 26679070 TI - Association between Liver Disease and Intracranial Hemorrhage. AB - BACKGROUND: Liver disease is common and associated with clinical and laboratory evidence of coagulopathy. The association between liver disease and intracranial hemorrhage (ICH) remains unclear. Our aim was to assess whether liver disease increases the risk of ICH. METHODS: We performed a retrospective cohort study based on administrative claims data from California, Florida, and New York acute care hospitals from 2005 through 2011. Of a random 5% sample, we included patients discharged from the emergency department or hospital after a diagnosis of liver disease and compared them to patients without liver disease. Patients with cirrhotic liver disease were additionally analyzed separately. Kaplan-Meier survival statistics were used to calculate cumulative rates of incident ICH, and Cox proportional hazard analysis was used to adjust for demographic characteristics, vascular disease, and Elixhauser comorbidities. Multiple models tested the robustness of our results. RESULTS: Among 1,909,816 patients with a mean follow-up period of 4.1 (+/-1.8) years, the cumulative rate of ICH after a diagnosis of liver disease was 1.70% (95% confidence interval [CI], 1.55%-1.87%) compared to .40% (95% CI, .39%-.41%) in patients without liver disease (P <.001 by the log-rank test). Liver disease remained associated with an increased hazard of ICH after adjustment for demographic characteristics and vascular risk factors (hazard ratio [HR], 1.8; 95% CI, 1.6-2.0). This was attenuated in models additionally adjusted for general comorbidities (HR, 1.3; 95% CI, 1.2-1.5). CONCLUSIONS: There is a modest, independent association between liver disease and the risk of ICH. PMID- 26679079 TI - Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes. AB - AIM: To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). METHODS: A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. RESULTS: In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 +/- 1.98 vs 5.48 +/- 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 +/- 0.34 vs 2.50 +/ 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 +/- 0.19 vs 0.84 +/- 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 +/- 1.04 vs 9.17 +/- 1.26 pools/day; p = 0.79). CONCLUSIONS: ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM. PMID- 26679080 TI - Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis. AB - Multi-wall carbon nanotubes (MWCNT) are a form of flexible fibrous nanomaterial with high electrical and thermal conductivity. However, 50-nm MWCNT in diameter causes malignant mesothelioma (MM) in rodents and, thus, the International Agency of Research on Cancer has designated them as a possible human carcinogen. Little is known about the molecular mechanism through which MWCNT causes MM. To elucidate the carcinogenic mechanisms of MWCNT in mesothelial cells, we used a variety of lysates to comprehensively identify proteins specifically adsorbed on pristine MWCNT of different diameters (50 nm, NT50; 100 nm, NT100; 150 nm, NT150; and 15 nm/tangled, NTtngl) using mass spectrometry. We identified >400 proteins, which included hemoglobin, histone, transferrin and various proteins associated with oxidative stress, among which we selected hemoglobin and transferrin for coating MWCNT to further evaluate cytotoxicity, wound healing, intracellular catalytic ferrous iron and oxidative stress in rat peritoneal mesothelial cells (RPMC). Cytotoxicity to RPMC was observed with pristine NT50 but not with NTtngl. Coating NT50 with hemoglobin or transferrin significantly aggravated cytotoxicity to RPMC, with an increase in cellular catalytic ferrous iron and DNA damage also observed. Knockdown of transferrin receptor with ferristatin II decreased not only NT50 uptake but also cellular catalytic ferrous iron. Our results suggest that adsorption of hemoglobin and transferrin on the surface of NT50 play a role in causing mesothelial iron overload, contributing to oxidative damage and possibly subsequent carcinogenesis in mesothelial cells. Uptake of NT50 at least partially depends on transferrin receptor 1. Modifications of NT50 surface may decrease this human risk. PMID- 26679081 TI - Nondestructive Optical Sensing of Flavonols and Chlorophyll in White Head Cabbage (Brassica oleracea L. var. capitata subvar. alba) Grown under Different Nitrogen Regimens. AB - A multiparametric optical sensor was used to nondestructively estimate phytochemical compounds in white cabbage leaves directly in the field. An experimental site of 1980 white cabbages (Brassica oleracea L. var. capitata subvar. alba), under different nitrogen (N) treatments, was mapped by measuring leaf transmittance and chlorophyll fluorescence screening in one leaf/cabbage head. The provided indices of flavonols (FLAV) and chlorophyll (CHL) displayed the opposite response to applied N rates, decreasing and increasing, respectively. The combined nitrogen balance index (NBI = CHL/FLAV) calculated was able to discriminate all of the plots under four N regimens (0, 100, 200, and 400 kg/ha) and was correlated with the leaf N content determined destructively. CHL and FLAV were properly calibrated against chlorophyll (R(2) = 0.945) and flavonol (R(2) = 0.932) leaf contents, respectively, by using a homographic fit function. The proposed optical sensing of cabbage crops can be used to estimate the N status of plants and perform precision fertilization to maintain acceptable crop yield levels and, additionally, to rapidly detect health-promoting flavonol antioxidants in Brassica plants. PMID- 26679082 TI - Uridine monophosphate, folic acid and vitamin B12 in patients with symptomatic peripheral entrapment neuropathies. AB - BACKGROUND: Carpal tunnel syndrome is the most common type of peripheral entrapment neuropathy. PATIENTS & METHODS: We performed an exploratory, open label, multicenter, observational study of 48 patients with peripheral entrapment neuropathy. Patients received a daily capsule of uridine monophosphate, folic acid + vitamin B12 for 2 months and were evaluated using the Pain DETECT questionnaire. RESULTS: The global score for pain decreased from 17.3 +/- 5.9 at baseline to 10.3 +/- 6.1 at the final evaluation (p < 0.001). Concomitant analgesic and anti-inflammatory treatment was stopped or the dose reduced in 77.4% of patients. CONCLUSION: Uridine monophosphate + folic acid + vitamin B12 reduced total pain score, intensity and characterization of pain and associated symptoms. These results should be tested in a well-designed, adequately powered randomized controlled trial. PMID- 26679083 TI - Complete mitochondrial genome of Coregonus muksum. AB - The complete mitochondrial genome of Coregonus muksum was determined in this study. The mitogenome is 16 736 bp in length and contains one D-loop region, 2 ribosomal RNA genes, 22 transfer RNA genes, and 13 protein-coding genes. The overall base composition of the heavy strand is 26.82% for A, 29.50% for C, 18.04% for G, and 25.68% for T. The percentage of G + C content is 47.54%. This is the first time of the mitochondrial genome sequencing for Coregonus muksum. PMID- 26679084 TI - Comprehensive assessment of the prognosis of pancreatic cancer: peripheral blood neutrophil-lymphocyte ratio and immunohistochemical analyses of the tumour site. AB - OBJECTIVE: Several studies have suggested that an elevated neutrophil-lymphocyte ratio (NLR) is associated with a poorer prognosis in patients with pancreatic cancer (PC). The correlations between the NLR and immunohistochemical (IHC) analysis with regard to the prognosis of patients with PC remain to be elucidated. By using IHC findings, we determined the value of the NLR as a prognostic factor in patients with PC. MATERIAL AND METHODS: We collected the clinico-pathological data of 28 consecutive patients who underwent surgical resection for PC between January 2008 and December 2012 at The Jikei University Kashiwa Hospital. We investigated whether the NLR and IHC results were related and ensured the consistency of the prognosis of patients with PC. RESULTS: The Kaplan-Meier curves for the disease-free survival (DFS) and the overall survival (OS) revealed that an NLR >= 5 is an implicit factor for decreased DFS and OS in patients with PC (p = 0.003, p < 0.001, log-rank test). The density of CD163(+) macrophages and CD66b(+) neutrophils was significantly higher in the high NLR group; on the contrary, the density of CD20(+) lymphocytes was significantly higher in the low NLR group. Moreover, a Mann-Whitney U test showed that the NLR was significantly correlated with a high density of CD20(+) lymphocytes (p = 0.031) and CD163(+) macrophages (p = 0.023), while the NLR was not significantly correlated with CD66b(+) neutrophils (p = 0.397). CONCLUSIONS: Our results demonstrated the validity of the NLR by IHC analyses and we determined that a higher value of NLR is a trustworthy prognostic factor for patients with PC. PMID- 26679085 TI - Nonselective chemokine levels in nasal secretions of patients with perennial nonallergic and allergic rhinitis. AB - BACKGROUND: An increased production of several chemoattractants, responsible for guiding the eosinophilic inflammatory process, has been reported in chronic rhinitis. The aim of this study was to evaluate nasal secretion levels of monocyte chemoattractant protein-1 (MCP-1), MCP-3, and regulated on activation normal T cell expressed and secreted (RANTES) and to correlate those levels with nasal symptoms and degree of eosinophilia in patients with nonallergic rhinitis with eosinophilia syndrome (NARES) and perennial allergic rhinitis (PAR). METHODS: Fourteen patients with PAR and 14 NARES patients were recruited for this cross-sectional study. Fourteen healthy subjects were included as controls. The concentrations of MCP-1, MCP-3, and RANTES in nasal secretions were measured using enzyme-linked immunosorbent assay (ELISA). Eosinophil counts were performed by percentage of differential granulocyte counts during cytological examination of scraped nasal mucosa obtained from the inferior turbinate. Therefore, we scored rhinitis patients according to nasal symptom score. RESULTS: We found significantly higher concentrations of MCP-1 (p < 0.0001), MCP-3 (p = 0.018), and RANTES (p < 0.0001) in nasal fluid of NARES patients compared to patients with PAR. In PAR patients, we found positive correlation between RANTES levels and nasal symptom score and eosinophil counts. In patients with NARES, the concentrations of MCP-1 and RANTES were associated with nasal symptom score and percentage of eosinophils. CONCLUSION: NARES is characterized by higher degree of eosinophilic inflammation than PAR. RANTES correlates well with the level of eosinophilic inflammation in both diseases. The measurement of chemokine levels in nasal secretions could be useful in evaluating the degree of chronic nasal inflammation. PMID- 26679086 TI - Coil-globule transition of a single semiflexible chain in slitlike confinement. AB - Single polymer chains undergo a phase transition from coiled conformations to globular conformations as the effective attraction between monomers becomes strong enough. In this work, we investigated the coil-globule transition of a semiflexible chain confined between two parallel plates, i.e. a slit, using the lattice model and Pruned-enriched Rosenbluth method (PERM) algorithm. We find that as the slit height decreases, the critical attraction for the coil-globule transition changes non-monotonically due to the competition of the confinement free energies of the coiled and globular states. In wide (narrow) slits, the coiled state experiences more (less) confinement free energy, and hence the transition becomes easier (more difficult). In addition, we find that the transition becomes less sharp with the decreasing slit height. Here, the sharpness refers to the sensitivity of thermodynamic quantities when varying the attraction around the critical value. The relevant experiments can be performed for DNA condensation in microfluidic devices. PMID- 26679087 TI - Characterization of Th17 and FoxP3(+) Treg Cells in Paediatric Psoriasis Patients. AB - Psoriasis is one of the most common inflammatory skin conditions affecting both children and adults. Growing evidence indicates that T-helper 17 (Th17) cells and CD4(+) CD25(+) regulatory T (Treg) cells play an important role in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in paediatric psoriasis remain unclear. In this study, we found that both Th17 and FoxP3(+) Treg cells and the ratio of Th17 to Treg cell frequency in the peripheral circulation were increased in patients with paediatric psoriasis and were positively correlated with the disease severity. The function of Treg to suppress CD4(+) CD25(-) T cell proliferation and IFN gamma secretion was impaired during the onset of psoriasis. After disease remission, both the Th17 and Treg cell frequencies were decreased, and the suppressive function of the Treg cells was obviously restored. However, neither Treg cells from the disease onset nor those after remission can regulate IL-17 secretion by CD4(+) T cells. These findings will further our understanding of the associations between Th17 and Treg cells in paediatric psoriasis and their influence on disease severity. PMID- 26679088 TI - Controlled reverse pulse electrosynthesized spike-piece-structured Ni/Ni(OH)2 interlayer nanoplates for electrochemical pseudocapacitor applications. AB - An ultrathin Ni/Ni(OH)2 hybrid electrode has been synthesized using a controlled reverse pulse modulated electrochemical approach and demonstrated as an advanced pseudocapacitor material having a remarkable specific capacitance and excellent cycling performance. PMID- 26679089 TI - A Subgroup Analysis of Chinese Patients Switched to Paliperidone Palmitate One Month Injectable by Prior Oral Antipsychotic Treatment. AB - INTRODUCTION: Safely tapering current antipsychotic medication, while balancing efficacy and tolerability, is an important consideration when switching patients from their antipsychotic therapy to a new treatment. The efficacy and tolerability of paliperidone palmitate one-month (PP1M) in Chinese patients switched from previous antipsychotic treatments were examined in order to develop effective switching and dosing strategies. METHODS: A 13-week open-label, single arm, prospective, interventional study was conducted in Chinese patients (n = 610) with acute schizophrenia to examine their response, by previous treatment group, when switched to PP1M (75-150 mg eq). RESULTS: Among 610 patients with >= 30% reduction in PANSS total score were 191/263 (72.6%) risperidone/paliperidone extended-release patients, 36/52 (69.2%) olanzapine patients, and 214/293 (73.0%) other antipsychotic patients. Patient functioning and adherence were significantly (p <= 0.05) improved for all subgroups. DISCUSSION: Patients on higher doses of prior antipsychotics generally took longer to withdraw from their current medication. Most patients were administered the 100 mg eq dose, and all subgroups received a similar mean dose (114-119 mg eq) of PP1M. Recommendations for transitioning patients to PP1M from each subgroup are discussed. PMID- 26679090 TI - Decreased elastic fibers and increased proteoglycans in the ligamentum flavum of patients with lumbar spinal canal stenosis. AB - Elastic fibers and proteoglycans are major components of the extracellular matrix and their changes have been reported in some pathological conditions. Further, recent studies have indicated that some glycosaminoglycans and proteoglycans inhibit elastic fiber assembly. The purpose of this study was to investigate changes of the elastic fibers and proteoglycans in the ligamentum flavum and analyze their relationships to thickening of the ligamentum flavum from lumbar spinal canal stenosis (LSCS). Ligamentum flavum samples were collected from 20 patients with LSCS (thickened flavum group) and 10 patients with lumbar disc herniation (non-thickened flavum group) as a control. Elastica-Masson staining and alcian blue staining were used to compare the relationship between the changes in the elastic fibers and proteoglycans. Gene and protein expressions of the elastic fibers and proteoglycans were analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Histological changes indicated that proteoglycans mainly increased on the dorsal side of the ligamentum flavum in accordance with the decreased elastic fibers in the thickened flavum group. The gene and protein expressions of fibrillin-2 and DANCE were significantly lower and decorin, lumican, osteoglycin, and versican were significantly higher in the thickened flavum group. Our study shows that elastic fibers decrease and proteoglycans increase in the thickened ligamentum flavum. Decreased gene expression of elastogenesis and disrupted elastic fiber assembly caused by increased proteoglycans may lead to a loss of elasticity in the thickened ligamentum flavum. Decreased elasticity may cause buckling of the tissue, which leads to thickening of the ligamentum flavum. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1241-1247, 2016. PMID- 26679091 TI - Driving ability after right-sided ankle arthroscopy--A prospective Study. AB - INTRODUCTION: Due to the current lack of evidence the aim of this study was to investigate the driving ability after right-sided ankle arthroscopy. MATERIALS AND METHODS: Nineteen patients underwent right-sided ankle arthroscopy. Brake response time (BRT) was assessed preoperatively, 2 days, 2 weeks, 6 weeks, and 12 weeks postoperative. We also determined patients' clinical outcome (AOFAS and AOS questionnaires) and their driving frequency. RESULTS: BRT was 606ms preoperatively and changed to 821ms 2 days postoperative (p<0.001). The further postoperative BRT course was 606ms (2 weeks), 596ms (6 weeks) and 603ms (12 weeks) (p=n.s.). In addition, a significant influence of the AOS and AOFAS scores on BRT was found, namely poorer clinical outcome also leads to a prolonged BRT (p<0.01 for both). BRT was significantly prolonged in patients with little driving frequency (p=0.001). Furthermore, the 'time-by-driving interaction' was significant (p=0.018), which means the BRT-peak on the second day was much lower in low-frequency drivers. CONCLUSIONS: From the findings made in the current study we conclude that a driving abstinence of two weeks is necessary following right-sided ankle arthroscopy. Greater driving frequency and good clinical outcome seem to be associated with better driving ability. However, for the time being no exceptions should be made from the above-mentioned recommendation on driving abstinence. PMID- 26679092 TI - Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data. AB - BACKGROUND: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. RESULTS: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. CONCLUSIONS: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes. PMID- 26679093 TI - Pro-oxidant-antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders. AB - OBJECTIVE: Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant antioxidant balance (PAB) assay in human serum of SM-exposed patients. DESIGN AND METHODS: sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured. RESULTS: SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74 +/- 21.07 HK, 101.45 +/- 32.68 HK and 120.23 +/- 31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV1. CONCLUSIONS: The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress. PMID- 26679094 TI - Combined liver mobilization and retraction: A novel technique to obtain the optimal surgical field during laparoscopic total gastrectomy. AB - INTRODUCTION: During laparoscopic gastrectomy, it is important to establish a good operative field and ensure an adequate working space. The combined liver mobilization and retraction method is used to get a safe and optimal view. METHODS: We retrospectively analyzed 32 consecutive patients who underwent laparoscopic total gastrectomy for gastric cancer. The patients were divided into two groups: the mobilization (+) group (n = 12) and the mobilization (-) group (n = 20). Hepatic function tests were performed in all patients. RESULTS: Mobilization provided a satisfactory view of the working field, especially the gastroesophageal junction and the angle of His during laparoscopic total gastrectomy, and no complications were observed during liver retraction. On postoperative hepatic function testing, there was no significant difference between the two groups on any day. CONCLUSIONS: Combined liver mobilization and retraction may be helpful in laparoscopic total gastrectomy. PMID- 26679095 TI - PDLIM1 inhibits NF-kappaB-mediated inflammatory signaling by sequestering the p65 subunit of NF-kappaB in the cytoplasm. AB - Understanding the regulatory mechanisms for the NF-kappaB transcription factor is key to control inflammation. IkappaBalpha maintains NF-kappaB in an inactive form in the cytoplasm of unstimulated cells, whereas nuclear NF-kappaB in activated cells is degraded by PDLIM2, a nuclear ubiquitin E3 ligase that belongs to a LIM protein family. How NF-kappaB activation is negatively controlled, however, is not completely understood. Here we show that PDLIM1, another member of LIM proteins, negatively regulates NF-kappaB-mediated signaling in the cytoplasm. PDLIM1 sequestered p65 subunit of NF-kappaB in the cytoplasm and suppressed its nuclear translocation in an IkappaBalpha-independent, but alpha-actinin-4 dependent manner. Consistently, PDLIM1 deficiency lead to increased levels of nuclear p65 protein, and thus enhanced proinflammatory cytokine production in response to innate stimuli. These studies reveal an essential role of PDLIM1 in suppressing NF-kappaB activation and suggest that LIM proteins comprise a new family of negative regulators of NF-kappaB signaling through different mechanisms. PMID- 26679096 TI - A robust, melting class bulk superhydrophobic material with heat-healing and self cleaning properties. AB - Superhydrophobic (SH) materials are essential for a myriad of applications such as anti-icing and self-cleaning due to their extreme water repellency. A single, robust material simultaneously possessing melt-coatability, bulk water repellency, self-cleanability, self-healability, self-refreshability, and adhesiveness has been remaining an elusive goal. We demonstrate a unique class of melt-processable, bulk SH coating by grafting long alkyl chains on silica nanoparticle surface by a facile one-step method. The well-defined nanomaterial shows SH property in the bulk and is found to heal macro-cracks on gentle heating. It retains wettability characteristics even after abrading with a sand paper. The surface regenerates SH features (due to reversible self-assembly of nano structures) quickly at ambient temperature even after cyclic water impalement, boiling water treatment and multiple finger rubbing tests. It exhibits self-cleaning properties on both fresh and cut surfaces. This kind of coating, hitherto undisclosed, is expected to be a breakthrough in the field of melt-processable SH coatings. PMID- 26679097 TI - In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy. AB - OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology. PMID- 26679098 TI - Febuxostat-induced acute liver injury. PMID- 26679099 TI - On the suitability of Thiel-fixed samples for biomechanical purposes: Critical considerations on the articles of Liao et al. "Elastic Properties of Thiel Embalmed Human Ankle Tendon and Ligament" and Verstraete et al. "Impact of Drying and Thiel Embalming on Mechanical Properties of Achilles Tendons". PMID- 26679100 TI - Vitamin D and autoimmune rheumatic disease. PMID- 26679101 TI - Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance. AB - The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Delta9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Delta9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. PMID- 26679102 TI - ProKaSaRe Study Protocol: A Prospective Multicenter Study of Pulmonary Rehabilitation of Patients With Sarcoidosis. AB - BACKGROUND: Available data assessing the efficacy of pulmonary rehabilitation for patients with chronic sarcoidosis are scant; for Germany, there are none at all. OBJECTIVE: To gain information about the benefit of in-house pulmonary rehabilitation for patients with chronic sarcoidosis and for the health care system, we intend to collect data in a prospective multicenter "real-life" cohort trial. METHODS: ProKaSaRe (Prospektive Katamnesestudie Sarkoidose in der pneumologischen Rehabilitation) [Prospective Catamnesis Study of Sarcoidosis in Pulmonary Rehabilitation] will assess a multimodal 3-week inpatient pulmonary rehabilitation program for adult patients with chronic sarcoidosis over a 1-year follow-up time. Defined specific clinical measurements and tests will be performed at the beginning and the end of the rehabilitation. In addition, questionnaires concerning health-related quality of life and the patients' symptoms will be provided to all patients. Inclusion criteria will be referral to one of the 6 participating pulmonary rehabilitation clinics in Germany for sarcoidosis and age between 18 and 80 years. Patients will only be excluded for a lack of German language skills or the inability to understand and complete the study questionnaires. To rule out seasonal influences, the recruitment will take place over a period of 1 year. In total, at least 121 patients are planned to be included. A descriptive statistical analysis of the data will be performed, including multivariate analyses. The primary outcomes are specific health-related quality of life (St George's Respiratory Questionnaire) and exercise capacity (6 minute walk test). The secondary outcomes are several routine lung function and laboratory parameters, dyspnea scores and blood gas analysis at rest and during exercise, changes in fatigue, psychological burden, and generic health-related quality of life (36-item Short Form Health Survey). RESULTS: Funding was obtained on October 12, 2010; enrollment began on January 15, 2011 and was completed by January 14, 2012. Results are anticipated late summer 2015. CONCLUSIONS: Due to the large number of participants, we expect to obtain representative findings concerning the effectiveness of pulmonary rehabilitation for patients with sarcoidosis and to provide a dataset of assessed objective and subjective short- and long-term changes due to pulmonary rehabilitation. The results should form the basis for the planning of a randomized controlled trial. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00000560; https://drks-neu.uniklinik freiburg.de/ drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000560 (Archived by WebCite(r) at http://www.webcitation.org/6dKb5X87R). PMID- 26679103 TI - Effects of central sympathetic activation on repolarization-dispersion during short-term myocardial ischemia in anesthetized rats. AB - AIMS: Sympathetic activation during myocardial ischemia enhances arrhythmogenesis, but the underlying pathophysiologic mechanisms remain unclear. We investigated the central sympathetic effects on ventricular repolarization during the early-period post-coronary artery occlusion. MAIN METHODS: We studied 12 Wistar rats (254+/-2 g) for 30 min following left coronary artery ligation, with (n=6) or without (n=6) pretreatment with the central sympatholytic agent clonidine. Mapping of left and right ventricular epicardial electrograms was performed with a 32-electrode array. As an index of sympathetic activation, heart rate variability in the frequency domain was calculated. Heart rate and repolarization duration were measured with a custom-made recording and analysis software, followed by calculation of intra- and inter-ventricular dispersion of repolarization. KEY FINDINGS: Heart rate and heart rate variability indicated lower sympathetic activation in clonidine-treated rats during ischemia. Repolarization duration in the left ventricle prolonged after clonidine at baseline, independently of heart rate, but no differences were present 30 min post-ligation. Dispersion of repolarization in the right ventricle remained stable during ischemia, whereas it increased in the left ventricle, equally in both groups. A similar trend was observed for inter-ventricular dispersion, without differences between groups. SIGNIFICANCE: In addition to intra ventricular repolarization-dispersion, anterior-wall myocardial ischemia may also increase inter-ventricular repolarization-dispersion. Progressive central sympathetic activation occurs during myocardial ischemia, but it does not affect intra- or inter-ventricular dispersion of ventricular repolarization during the early phase. Further research is warranted on the potential effects during subsequent time-periods. PMID- 26679105 TI - Evidence for possible role of melatonin in reducing oxidative stress in multiple sclerosis through its effect on SIRT1 and antioxidant enzymes. AB - AIMS: Oxidative stress plays a crucial role in the pathogenesis of multiple sclerosis (MS). Melatonin has a central role in the modulation of oxidative stress pathways. We aimed to investigate the effect of melatonin on mRNA expression and activity of sirtuin1 (SIRT1) and its target genes, manganese superoxide dismutase (MnSOD), and catalase in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy subjects. KEY METHODS: This study was performed on 12 patients with relapsing-remitting MS (RRMS) and 14 age- and sex matched healthy subjects. PBMCs were isolated and treated with pharmacological concentration of melatonin (1mM) for 12h. Gene expression was evaluated by real time-PCR. SIRT1 activity in PBMCs was measured using a fluorometric assay. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Plasma total antioxidant capacity was measured using the ferric reducing ability of plasma assay. KEY FINDINGS: Melatonin significantly increased activities and mRNA levels of SIRT1 and catalase in both patients and healthy subjects, whereas melatonin treatment caused a pronounced increase in MnSOD mRNA expression and activity only in patients. In MS patients, SIRT1 activity did not correlate with catalase and MnSOD activities before melatonin treatment, while a significant correlation was observed between SIRT1 activity and catalase activity in PBMCs of patients after melatonin treatment. SIGNIFICANCE: It appears that the antioxidant status is affected in PBMCs from MS patients and melatonin could improve impaired antioxidant defense in MS through upregulation of SIRT1, MnSOD and catalase, which might be important in MS management. PMID- 26679104 TI - Triptolide attenuated injury via inhibiting oxidative stress in Amyloid-Beta25-35 treated differentiated PC12 cells. AB - BACKGROUND: Recently, an abnormal deposition of Amyloid-Beta (Abeta) was considered the primary cause of the pathogenesis of Alzheimer's disease (AD). And how to inhibit the cytotoxicity is considered an important target for the treatment of AD. Triptolide (TP), a purified diterpenoid from the herb Tripterygium wilfordii Hook.f. (TWHF), has potential neuroprotective effects pertinent to disease of the nervous system. However, whether triptolide and its specific mechanisms have protective functions in differentiated PC12 cells treated with Abeta25-35 remain unclear. AIMS: The purpose is to investigate the protective functions of triptolide in Abeta25-35-stimulated differentiated PC12 cells. MAIN METHODS: In the study, we use 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, flow cytometry assay, immunohistochemical staining and Western blot to observe the effects of triptolide on cytotoxicity induced by Abeta25-35 and its mechanism of oxidative stress. KEY FINDINGS: The result of MTT and LDH assay indicates that triptolide protected PC12 cells against Abeta25-35-induced cytotoxicity. The flow cytometry assay shows that triptolide attenuated Abeta25-35-induced apoptosis in differentiated PC12 cells. Meanwhile, the results give a clear indication that triptolide could downregulate generation of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA) induced by Abeta25-35. The apoptotic process triggered by triptolide involved the up-regulation of the activity of superoxide dismutase (SOD). SIGNIFICANCE: The results suggest that triptolide may serve as an important role in the inhibition of the cell apoptosis induced by Abeta and the decreased oxidative stress is a key mechanism in the protective effect of triptolide in AD. PMID- 26679106 TI - Chemopreventive agents targeting tumor microenvironment. AB - Recent studies have shown that tumor development and progression depend not only on the perturbed genes that govern cell proliferation, but is also highly determined by the non-tumor cells of the stromal compartment surrounding the tumor called tumor microenvironment (TME). These findings highlight the importance of targeting the microenvironment in combination with therapies aimed at tumor cells as a valuable approach. The innate and adaptive immune cells in the TME interact among themselves and also with the endothelial cells, pericytes and mast cells of the stromal compartment through various autocrine and paracrine manner to regulate abnormal cell proliferation. Direct cytotoxic killing of cancer cells and/or reversion of the immunosuppressive TME are to be considered as better strategies for chemoprevention and chemotherapy. With a growing emphasis on a "hallmark targeting" strategy for cancer therapy, the TME now appears as a promising target for cancer prevention using natural products. Clarification on the nontumor stromal cells, the mediators involved, interactions with immune response cells, and immune-evasive mechanisms are needed in order to manipulate the characteristics of the TME by natural pharmacological agents to design effective therapies. This review will provide a glimpse on the roles played by various non-tumor cells in tumor progression and their intervention by pharmacological agents. PMID- 26679107 TI - ATP releases ATP or other nucleotides from human peripheral blood leukocytes through purinergic P2 receptors. AB - AIMS: Almost every eukaryotic cell releases ATP under certain conditions. The idea that ATP induces the release of ATP has been scantly investigated. METHODS: We explored this possibility by assessing the rate of exogenous ATP breakdown (measured by phosphates production) by human peripheral blood leukocytes. The role of P2Y and P2X receptors was evaluated pharmacologically, by patch clamp, or by flow cytometry. KEY FINDINGS: In mononuclear and/or polymorphonuclear cells, ATP increased phosphates formation in a time- and concentration-dependent manner. Uncoupling of P2Y receptors with N-ethylmaleimide and antagonism of P2Y and P2X receptors through suramin reduced phosphate formation after 500MUM ATP, suggesting that part of the phosphate production was due to activation of P2 receptors, with subsequent release of ATP or other nucleotides. Similar results were obtained with UTP and ATPgammaS. Gadolinium (connexins inhibitor) also significantly reduced the ATP-induced phosphate production. Blockade of P2X receptors with SKF 96365 or NF023 did not modify the phosphate production. In monocytes, 500MUM ATP induced inward currents suggestive of P2X1 activation, but higher concentrations (1-5mM) induced inward currents suggestive of P2X7 activation. We discarded a role of adenosine in the ATP-evoked nucleotides release. Flow cytometry identified that almost all mononuclear and polymorphonuclear cells expressed P2Y1,2,4,6,11 receptors. SIGNIFICANCE: 500MUM ATP induced the release of ATP or other nucleotides through activation of P2Y2,4,6,11 receptors in human leukocytes, and probably via P2X receptors at higher concentrations. This ATP-induced nucleotides release constitutes a potential mechanism leading to amplification of ATP signaling. PMID- 26679109 TI - The Occupational Profile of Women with Fibromyalgia Syndrome. AB - The aims of this study were to assess the functional level of women with fibromyalgia; to investigate the differences in the occupational activities between women with fibromyalgia and healthy women; and to analyse the perceived importance of occupational performance during self-care, productivity and leisure activities. A cross-sectional case control study was performed. Twenty women with fibromyalgia and 20 healthy women completed the Functional Independence Measure (FIM), the Canadian Occupational Performance Measure (COPM), a Numerical Pain Rating Scale, the Fibromyalgia Impact Questionnaire and the SF-36 health survey. The Chi-square test (chi2), the Student's t test and the Spearman's test were used on the data. The FIM revealed significant differences regarding several activities: personal hygiene, bathing and memory (p < 0.01). The COPM scores did not reveal significant differences between groups (p > 0.10). Women with fibromyalgia had higher disability and reduced quality of life and required greater assistance to perform specific activities of daily living, i.e. hygiene, than healthy women. This highlights the specific occupational therapy needs these women have for performing many basic activities and for improving their quality of life. Limitations of the study include the small sample size, the exclusion of male participants and the possible influence of the women's psychological status on the assessments performed. Findings should be generalized with caution. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26679108 TI - Anti-fibrotic effect of pirfenidone in muscle derived-fibroblasts from Duchenne muscular dystrophy patients. AB - AIMS: Tissue fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the end point of diseases affecting the kidney, bladder, liver, lung, gut, skin, heart and muscle. In Duchenne muscular dystrophy (DMD), connective fibrotic tissue progressively substitutes muscle fibers. So far no specific pharmacological treatment is available for muscle fibrosis. Among promising anti-fibrotic molecules, pirfenidone has shown anti-fibrotic and anti inflammatory activity in animal and cell models, and has already been employed in clinical trials. Therefore we tested pirfenidone anti-fibrotic properties in an in vitro model of muscle fibrosis. MAIN METHODS: We evaluated effect of pirfenidone on fibroblasts isolated from DMD muscle biopsies. These cells have been previously characterized as having a pro-fibrotic phenotype. We tested cell proliferation and migration, secretion of soluble collagens, intracellular levels of collagen type I and fibronectin, and diameter of 3D fibrotic nodules. KEY FINDINGS: We found that pirfenidone significantly reduced proliferation and cell migration of control and DMD muscle-derived fibroblasts, decreased extracellular secretion of soluble collagens by control and DMD fibroblasts, as well as levels of collagen type I and fibronectin, and, in DMD fibroblasts only, reduced synthesis and deposition of intracellular collagen. Furthermore, pirfenidone was able to reduce the diameter of fibrotic-nodules in our 3D model of in vitro fibrosis. SIGNIFICANCE: These pre-clinical results indicate that pirfenidone has potential anti-fibrotic effects also in skeletal muscle fibrosis, urging further studies in in vivo animal models of muscular dystrophy in order to translate the drug into the treatment of muscle fibrosis in DMD patients. PMID- 26679110 TI - Co-expression of heat shock protein (HSP) 40 and HSP70 in Pinctada martensii response to thermal, low salinity and bacterial challenges. AB - Heat shock protein (HSP) 40 proteins are a family of molecular chaperones that bind to HSP70 through their J-domain and regulate the function of HSP70 by stimulating its adenosine triphosphatase activity. In the present study, a HSP40 homolog named PmHSP40 was cloned from the hemocytes of pearl oyster Pinctada martensii using EST and rapid amplification of cDNA ends (RACE) techniques. The full-length cDNA of PmHSP40 was 1251 bp in length, which included a 5' untranslated region (UTR) of 75 bp, an open reading frame (ORF) of a 663 bp, and a 3' UTR of 513 bp. The deduced amino acid sequence of PmHSP40 contains a J domain in the N-terminus. In response to thermal and low salinity stress challenges, the expression of PmHSP40 in hemocytes and the gill were inducible in a time-dependent manner. After bacterial challenge, PmHSP40 transcripts in hemocytes increased and peaked at 6 h post injection. In the gill, PmHSP40 expression increased, similar to expression in hemocytes; however, transcript expression of PmHSP40 was significantly up-regulated at 12 h post injection. Furthermore, the transcripts of PmHSP70 showed similar kinetics as that of PmHSP40, with highest induction during thermal, low salinity stress and bacterial challenges. Altogether these results demonstrate that PmHSP40 is an inducible protein under thermal, low salinity and bacterial challenges, suggesting its involvement in both environmental and biological stresses, and in the innate immunity of the pearl oyster. PMID- 26679112 TI - Apoptosis in Drosophila: which role for mitochondria? AB - It is now well established that the mitochondrion is a central regulator of mammalian cell apoptosis. However, the importance of this organelle in non mammalian apoptosis has long been regarded as minor, mainly because of the absence of a crucial role for cytochrome c in caspase activation. Recent results indicate that the control of caspase activation and cell death in Drosophila occurs at the mitochondrial level. Numerous proteins, including RHG proteins and proteins of the Bcl-2 family that are key regulators of Drosophila apoptosis, constitutively or transiently localize in mitochondria. These proteins participate in the cell death process at different levels such as degradation of Diap1, a Drosophila IAP, production of mitochondrial reactive oxygen species or stimulation of the mitochondrial fission machinery. Here, we review these mitochondrial events that might have their counterpart in human. PMID- 26679113 TI - Contracts: Junior doctors and the NHS. PMID- 26679111 TI - Embryonic transcription is controlled by maternally defined chromatin state. AB - Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, which we use to determine the extent to which maternal factors shape chromatin state in Xenopus embryos. Using alpha-amanitin to inhibit zygotic transcription, we find that the majority of H3K4me3- and H3K27me3-enriched regions form a maternally defined epigenetic regulatory space with an underlying logic of hypomethylated islands. This maternal regulatory space extends to a substantial proportion of neurula stage-activated promoters. In contrast, p300 recruitment to distal regulatory regions requires embryonic transcription at most loci. The results show that H3K4me3 and H3K27me3 are part of a regulatory space that exerts an extended maternal control well into post-gastrulation development, and highlight the combinatorial action of maternal and zygotic factors through proximal and distal regulatory sequences. PMID- 26679114 TI - Case reports: Palatal mucosal necrosis after administration of a palatal infiltration. PMID- 26679115 TI - Radiography: Left or right? Plate orientation. PMID- 26679116 TI - In practice: Impact on the airway. PMID- 26679117 TI - Implantology: The real McCoy. PMID- 26679118 TI - Denplan welcomes Osborne's report on empowering dental patients to make the best choices. PMID- 26679120 TI - Dentists relieved at end to impasse on junior contract. PMID- 26679122 TI - ARF freeze a choice, not a necessity. PMID- 26679123 TI - Sugar tax report puts real pressure on ministers for decisive action. PMID- 26679124 TI - Conference round-up: Belfast hosts International Restorative Dentistry Conference. PMID- 26679125 TI - Accessing the missing thirty percent of English children who don't see a dentist. PMID- 26679126 TI - New patient advice resource launched. PMID- 26679129 TI - Help defeat MDS and blood cancer. PMID- 26679131 TI - The tribulations of toothpaste trials: Unethical arginine dentifrice research. AB - Arginine toothpaste is being promoted as being more efficacious than conventional fluoride-only toothpaste. Recent revelations concerning the design and conduct of the clinical trials conducted on schoolchildren in China and Thailand cast serious doubt on these claims. This paper describes and analyses the ethical and design flaws affecting these studies. PMID- 26679136 TI - Assessing sedation need and managing referred dentally anxious patients: is there a role for the Index of Sedation Need? AB - AIM: To conduct an exploratory investigation of public dental service (PDS) practitioners' planned sedation modality using a structural equation modelling approach, in order to identify the explanatory value of using the Index of Sedation Need (IOSN), or its component parts, to predict sedation modality in patients referred with dental anxiety. METHODS: A convenience sample of patients referred to the PDS for dental anxiety management was invited to take part. The IOSN was completed for each patient (patient dental anxiety, medical and behavioural indicators and dental treatment complexity) as well as the American Society of Anesthesiologists Physical Status Classification System and the Case Mix Tool. The practitioners completed details of their planned sedation modality and identified normative dental treatment need. The data were entered onto an SPSS v21 database and subjected to frequency distributions, t-tests, correlation analysis and exploratory partial structural equation modelling (SEM). RESULTS: Ninety-five percent of patients were ranked as MDAS 3 or 4, indicating high dental anxiety; 69% had a medical condition, which might impact on dental treatment and 82% had a dental treatment need, which was classified as intermediate/complex according to the IOSN. Eighty-eight percent of the patients in accordance with the IOSN required sedation: 62% of patients were assessed as requiring intravenous sedation. The IOSN discriminated between patients who were assessed as requiring more complex sedation modalities and had a greater normative treatment need. The SEM showed that the patient dental anxiety (P <0.02) and dental treatment complexity (P <0.02) predicted planned sedation modality. Functional morbidity was less strong, as a predictor, and was significant at the ten percent level. CONCLUSIONS: The IOSN is a useful and valid assessment of sedation need and predicted sedation modality for patients referred with high dental anxiety states and secondly, that component parts of the IOSN add explanatory value in practitioners' choice of planned sedation modality. PMID- 26679137 TI - A practice-based assessment of patients' knowledge of dental materials. AB - AIMS: It is the aim of this study to determine, by means of a questionnaire completed by patients attending ten UK dental practices, patients' level of knowledge on dental materials and techniques. MATERIALS AND METHODS: Members of The PREP (Product Research and Evaluation by Practitioners) Panel were asked to recruit patients to participate in a questionnaire-based assessment of their knowledge of dental materials. RESULTS: Two hundred and forty-nine patients took part in the questionnaire. Sixty-three percent (n = 157) of the respondents were female and 92% (n = 229) of the respondents stated they were regular attenders at the dental practice. The respondents were asked how important the quality of dental materials used in their mouth was, and on a Visual Analogue Scale (VAS) where 1 = not important and 10 = very important, the result was 9.6. The same score was recorded when they were asked how important it was that the materials used in their mouth were supported with relevant clinical research evidence and long term data of the success of the material. They were also questioned on the subjects of price, manufacturer, source or material and type of filling material. A significant amount of respondents demonstrated that they had concerns over the use of amalgam. CONCLUSIONS: Respondents expressed strong views that the materials used on their teeth should have a robust evidence base and they care about the materials that are used in their mouths. PMID- 26679138 TI - Case report: A medieval case of molar-incisor-hypomineralisation. AB - INTRODUCTION: Molar-incisor-hypomineralisation (MIH) has been identified in recent years as a condition affecting the first permanent molars and, in some cases, the permanent incisors. Many factors have been suggested as to its aetiology. Examples of MIH have also been reported in skeletal remains in the past. These historical examples have, however, been for unknown individuals. CASE REPORT: A skull that has become available for dental examination that is uncertainly attributed to be that of Lady Eleanor Talbot (c.1436-1468) who ended her life as a Carmelite nun in Norwich (England). The dental findings of the examination showed enamel defects of molar teeth 36 and 46, as well as small areas on other molars, and striations of the enamel of permanent anterior teeth consistent with MIH. There is exposure of the roots of some maxillary teeth with resultant root caries. The presence of areas of enamel decalcification commensurate with 'Turner teeth' on 43 and 44 indicates that there were likely to have been periapical abscesses secondary to dental caries of the primary teeth. In addition, there is occlusal wear of all of teeth with extensive calculus and periodontal exposure of the roots of the mandibular incisors. Failed development or very early ante-mortem loss of premolars 15 and 25 is evident, as well as evidence in the same region of a large abscess cavity with extensive maxillary bone destruction. Healing cribra orbitalia, porosity, which is considered to be an indicator of nutritional stress, is visible on the superior aspect of the left orbit. CONCLUSION: A case of MIH is reported in a skull dating from the mid-15th century. PMID- 26679146 TI - Intergenerational violence in Burundi: Experienced childhood maltreatment increases the risk of abusive child rearing and intimate partner violence. AB - BACKGROUND: Experiencing abuse during childhood affects the psychological well being of individuals throughout their lives and may even influence their offspring by enhancing the likelihood of an intergenerational transmission of violence. Understanding the effects of childhood maltreatment on child-rearing practices and intimate partner violence might be of particular importance to overcome the consequences of violent conflicts in African societies. OBJECTIVE: Using Burundi as an example, we aimed to explore the associations between childhood maltreatment, intimate partner violence, perceived partner intimidation, gender and the probability of violently acting out against one's own children or romantic partner. METHODS: Amongst a sample of 141 men and 141 women in the capital of Burundi, we identified those who had biological children and those who lived or had lived in relationships. Using culturally appropriate instruments, we enquired about their exposure to childhood maltreatment and partner violence as well as their inclinations to act out violently. RESULTS: We found that childhood maltreatment and perceived partner intimidation were strong predictors for the perpetration of violence against children. Moreover, we found that women were more likely to use violence against children if they experienced partner violence and less likely to resort to violence if they felt intimidated. Men were more likely to perpetrate violence against their partner. Childhood maltreatment was again a strong predictor. The more women experienced partner violence, the more they fought back. CONCLUSIONS: Childhood maltreatment is a strong predictor for domestic violence and has to be addressed to interrupt the cycle of violence in post-conflict countries. PMID- 26679147 TI - Si Hybrid Solar Cells with 13% Efficiency via Concurrent Improvement in Optical and Electrical Properties by Employing Graphene Quantum Dots. AB - By employing graphene quantum dots (GQDs) in PEDOT: PSS, we have achieved an efficiency of 13.22% in Si/ PEDOT: PSS hybrid solar cells. The efficiency enhancement is based on concurrent improvement in optical and electrical properties by the photon downconversion process and the improved conductivity of PEDOT: PSS via appropriate incorporation of GQDs. After introducing GQDs into PEDOT: PSS, the short circuit current and the fill factor of rear-contact optimized hybrid cells are increased from 32.11 to 36.26 mA/cm(2) and 62.85% to 63.87%, respectively. The organic-inorganic hybrid solar cell obtained herein holds the promise for developing photon-managing, low-cost, and highly efficient photovoltaic devices. PMID- 26679149 TI - Adenovirus Specific Pre-Immunity Induced by Natural Route of Infection Does Not Impair Transduction by Adenoviral Vaccine Vectors in Mice. AB - Recombinant human adenovirus serotype 5 (HAd5V) vectors are gold standards of T cell immunogenicity as they efficiently induce also humoral responses to exogenous antigens, in particular when used in prime-boost protocols. Some investigators have shown that pre-existing immunity to adenoviruses interferes with transduction by adenoviral vectors, but the actual extent of this interference is not known since it has been mostly studied in mice using unnatural routes of infection and virus doses. Here we studied the effects of HAd5V-specific immune responses induced by intranasal infection on the transduction efficiency of recombinant adenovirus vectors. Of interest, when HAd5V immunity was induced in mice by the natural respiratory route, the pre existing immunity against HAd5V did not significantly interfere with the B and T cell immune responses against the transgene products induced after a prime/boost inoculation protocol with a recombinant HAd5V-vector, as measured by ELISA and in vivo cytotoxic T-cell assays, respectively. We also correlated the levels of HAd5V-specific neutralizing antibodies (Ad5NAbs) induced in mice with the levels of Ad5NAb titers found in humans. The data indicate that approximately 60% of the human serum samples tested displayed Ad5NAb levels that could be overcome with a prime-boost vaccination protocol. These results suggest that recombinant HAd5V vectors are potentially useful for prime-boost vaccination strategies, at least when pre-existing immunity against HAd5V is at low or medium levels. PMID- 26679150 TI - Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway. AB - Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. PMID- 26679151 TI - The myocardial architecture changes in persistent pulmonary hypertension of the newborn in an ovine animal model. AB - BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5 degrees in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION: Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described. PMID- 26679152 TI - Diode laser spectroscopy for noninvasive monitoring of oxygen in the lungs of newborn infants. AB - BACKGROUND: Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants. METHODS: Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode. RESULTS: Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of >3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight. CONCLUSION: The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care. PMID- 26679153 TI - The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice. METHODS: Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed. RESULTS: Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner. CONCLUSION: Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease. PMID- 26679154 TI - Risk factors of different congenital heart defects in Guangdong, China. AB - BACKGROUND: Limited studies have evaluated the risk factors for congenital heart defects (CHDs) in China and compared them for different types of CHDs. This study examined risk factors between isolated and multiple CHDs as well as among CHDs subtypes in Guangdong, Southern China. METHODS: This population-based case control study included 4,034 pairs of case and control infants enrolled in the Guangdong Registry of CHD study, 2004-2013. Multivariate logistic regression was used to compute adjusted odds ratios (ORs) while simultaneously controlling for confounders. RESULTS: Multiple maternal environmental exposures, including living in newly renovated rooms, residential proximity to main traffic, paternal smoking, and maternal occupation as manual worker, were significantly associated with CHDs with ORs ranging 1.30-9.43. Maternal perinatal diseases (including maternal fever, diabetes, influenza, and threatened abortion), maternal medication use (antibiotic use), advanced maternal age, low socioeconomic status, and paternal alcohol intake were also significantly associated with CHDs, with ORs ranging 1.60-3.96. Isolated CHDs and multiple defects have different profiles of risk factors, while subtype of CHD shares common risk factors. CONCLUSION: These results suggest that maternal environmental exposures/occupation and perinatal diseases/medication use were dominant risk factors associated with CHDs in Southern China. Isolated and multiple CHDs may have different etiologic factors. PMID- 26679155 TI - The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury. AB - BACKGROUND: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life. The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group. We now report the blindly assessed and analyzed treatment effects on electroencephalographic (EEG) outcomes (burst rate and spectral edge frequency 95% (SEF95)) and blood biomarkers of brain injury (S100beta, brain fatty acid-binding protein, and neuroketal). METHODS: One hundred and sixty-six extremely preterm infants were randomized to either experimental or control group. EEG was recorded at 64 h of age and blood samples were collected at 6 and 64 h of age. RESULTS: One hundred and thirty-three EEGs were evaluated. The two groups did not differ regarding burst rates (experimental 7.2 vs. control 7.7 burst/min) or SEF95 (experimental 18.1 vs. control 18.0 Hz). The two groups did not differ regarding blood S100beta, brain fatty acid-binding protein, and neuroketal concentrations at 6 and 64 h (n = 123 participants). CONCLUSION: Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers. PMID- 26679156 TI - Human milk glycosaminoglycans inhibit in vitro the adhesion of Escherichia coli and Salmonella fyris to human intestinal cells. AB - BACKGROUND: Breast-fed infants have a lower incidence of acute gastroenteritis due to the presence of several anti-infective factors in human milk. The aim of this work is to study the capacity of human milk glycosaminoglycans (GAGs) to inhibit the adhesion of some common pathogenic bacteria. METHODS: GAGs were isolated from a pool of milk samples collected from different mothers during the first month of lactation. Experiments were carried out to study the ability of GAGs to inhibit the adhesion of two intestinal micro-organisms (enteropathogenic Escherichia coli serotype 0119 and Salmonella fyris) to Caco-2 and Int-407 cell lines. RESULTS: The study showed that the GAGs had an anti-adhesive effect on the two pathogenic strains studied with different degrees of inhibition. In particular, in the presence of human milk GAGs, the adhesion of S. fyris to Caco 2 cells and to Int-407 cells of both tested strains was significantly reduced. CONCLUSION: Our results demonstrated that GAGs in human milk can be one of the important defensive factors against acute diarrheal infections in breast-fed infants. PMID- 26679158 TI - From the New Editor-in-Chief. PMID- 26679157 TI - Meconium-induced inflammation and surfactant inactivation: specifics of molecular mechanisms. AB - This review summarizes neonatal meconium aspiration syndrome in light of meconium induced inflammation and inflammatory surfactant inactivation, related to both endogenous and therapeutic exogenous surfactant. The wide effect of meconium on surfactant properties is divided into three points. Direct effect of meconium on surfactant properties refers mainly to fragmentation of dipalmitoylphosphatidylcholine and other surfactant phospholipids together with cleavage of surfactant proteins. Initiation of inflammatory response due to activation of receptors by yet unspecified compounds involves complement and Toll like receptor activation. A possible role of lung collectins, surfactant proteins A and D, which can exert both pro- and anti-inflammatory reactions, is discussed. Initiation of inflammatory response by specified compounds in meconium reflects inflammatory functioning of cytokines, bile acids, and phospholipases contained in meconium. Unifying sketch of many interconnections in all these actions aims at providing integrated picture of inflammatory surfactant inactivation. PMID- 26679159 TI - CD90 and CD105 expression in the mouse ovary and testis at different stages of postnatal development. AB - CD90 (i.e., THY1) and CD105 (i.e., endoglin) are glycoproteins known as mesenchymal stem cell markers that are expressed in various cell types including male and female gonadal cells. We aimed to determine ovarian and testicular expression of CD90 and CD105 in various cell types during postnatal development in mice. The present study was carried out on male (C57BL/6) and female (Balb/C) mice during critical stages of gonadal development. Immunohistochemical localization of CD90 and CD105 was determined in the ovaries obtained at postnatal days (PND) -1, -7, -21 and -60 and in the testes obtained at PND6, -8, 16, -20, -29, -32 and -88. The relative expression of CD90 and CD105 was evaluated by ImageJ software and data were analyzed by analysis of variance. The relative expression of CD90 and CD105 varied during postnatal development and increased significantly in the adult ovary (PND60) and testis (PND88) compared to the early postnatal gonads. In the ovaries, the expression of CD90 was significantly higher in somatic cells in comparison to germ cell compartments. In the testis, CD90 expression was greater in germ cells and Sertoli cells compared to other cell types. Expression of CD105 was higher in germ cells than somatic cells of both the ovary and testis. In addition to different expression of CD90 and CD105 during various developmental stages, also their altered expression in particular cell types suggests specific roles of these glycoproteins in physiological processes of mouse gonads. PMID- 26679160 TI - Evidence for a role of ferritin heavy chain in mediating reproductive processes of geese. AB - Ferritin heavy chain (FHC), which exhibits ferroxidase activity and mediates the primary functions of ferritin, plays a role in regulating reproduction in animals. However, the changes in the FHC mRNA and protein levels in the HPG axis of geese remain to be determined. In the current study, FHC mRNA expression level was quantitatively monitored in the hypothalamus, anterior pituitary and ovary stroma in prelaying and laying geese. In addition, the levels of FHC mRNA and protein were determined in follicles and ovarian stroma of laying geese. In comparison to prelaying geese, the FHC mRNA expression were 2.4, 1.8, and 13 times higher in the hypothalamus, anterior pituitary and ovarian stroma of laying geese, respectively (p<0.05). FHC mRNA and protein were detected in all examined follicles and ovarian stroma. FHC mRNA expression was higher in postovulatory follicles (POFs) and atretic follicles than in developing follicles and ovarian stroma. Furthermore, the FHC protein concentration in POF3 and atretic follicles were, respectively, 1.45 and 1.7 times higher compared with that of F1 (p<0.05). In conclusion, the presented results provided evidence of a link between FHC and goose reproduction, and supplied a theoretical foundation and a new approach for studying reproduction, in particular ovarian follicular development in birds. PMID- 26679161 TI - Assessment of human embryos by time-lapse videography: A comparison of quantitative and qualitative measures between two independent laboratories. AB - A total of 488 Day 3 human embryos with known implantation data from two independent in vitro fertilization laboratories were included for analysis, with 270 from Fertility North (FN) and 218 from Canberra Fertility Centre (CFC). Implanting embryos grew at different rates between FN and CFC as indicated in hours of the time intervals between pronuclear fading and the 4- (13.9 +/- 1.1 vs. 14.9 +/- 1.8), 5- (25.7 +/- 1.9 vs. 28.4 +/- 3.7) and 8-cell stages (29.0 +/- 3.2 vs. 32.2 +/- 4.6), as well as the durations of 2- (10.8 +/- 0.8 vs. 11.6 +/- 1.1), 3- (0.4 +/- 0.5 vs. 0.9 +/- 1.2), and 4-cell stages (11.8 +/- 1.4 vs. 13.6 +/- 2.9), all p<0.05. The application of a previously published time-lapse algorithm on ICSI embryos from the two participating laboratories failed to reproduce a predictive pattern of implantation outcomes (FN: AUC=0.565, p=0.250; CFC: AUC=0.614, p=0.224). However, for the qualitative measures including poor conventional morphology, direct cleavage, reverse cleavage and <6 intercellular contact points at the end of the 4-cell stage, there were similar proportions of embryos showing at least one of these biological events in either implanting (3.1% vs. 3.3%, p>0.05) or non-implanting embryos (30.4% vs. 38.3%, p>0.05) between FN and CFC. Furthermore, implanting embryos favored lower proportions of the above biological events compared to the non-implanting ones in both laboratories (both p<0.01). To conclude, human embryo morphokinetics may vary between laboratories, therefore time-lapse algorithms emphasizing quantitative timing parameters may have reduced inter-laboratory transferability; qualitative measures are independent of cell division timings, with potentially improved inter-laboratory reproducibility. PMID- 26679162 TI - Killer cell immunoglobulin-like receptor gene association with cryptorchidism. AB - Cryptorchidism is a condition where a testis persists in the abdominal cavity. Thus, due to elevated temperature we may expect induction of aberrant immune reactions depending on genetic constitution of individual. This may be reflected by development of anti-sperm antibodies (ASA) in cryptorchid males. Also, natural killer (NK) cells which belong to innate immunity may control adaptive immunity. Therefore, the gene system encoding polymorphic NK cell immunoglobulin receptors (KIRs) has been studied. 109 prepubertal boys with cryptorchidism and 136 ethnically matched young male donors were selected to study NK cell KIRs. DNA was isolated using automatic Maxwell((r)) system from the peripheral venous blood drawn onto anticoagulant. Olerup SSP KIR Genotyping kit including Taq polymerase was used for detection of KIR genes. Human leukocyte antigen-C (HLA-C) groups, C1 and C2 were established using a Olerup SSP KIR HLA Ligand kit. KIR2DL2 (killer immunoglobulin-like receptor two-domain long 2) and KIR2DS2 (killer immunoglobulin-like receptor two-domain short 2) genes were less frequent in patients than in control individuals (corrected p values: 0.0110 and 0.0383, respectively). However, no significant differences were observed between ASA positive and ASA-negative patients, or between bilateral or unilateral cryptorchidism. No association between KIR ligands C1 and C2, alone or together with KIR2DL2, was found. However, the results suggest that KIR2DL2+/KIR2DS2+ genotype may be, to some extent, protective against cryptorchidism. PMID- 26679163 TI - Sperm characteristics following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins in the collared peccary (Pecari tajacu). AB - The aim of the current study was to compare sperm quality characteristics of the collared peccary (Pecari tajacu) following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins (LDL). Semen from 11 adult males was obtained by electroejaculation and evaluated for sperm motility, vigor, morphology as well as membrane integrity analyzed by the hypo-osmotic swelling (HOS) test and a fluorescent staining. Moreover, the semen was diluted in a Tris-based extender containing 20% egg yolk (control group) or 5, 10 or 20% LDL (treatment groups). The semen samples were frozen in liquid nitrogen and thawed in a water bath for 60s at 37 degrees C. The treatments did not affect (p>0.05) sperm vigor, morphology or membrane integrity analyzed by the HOS test. However, post-thaw sperm motility was significantly higher (p<0.05) in the extender supplemented with 20% LDL (36.4 +/- 5.3%) compared with the egg yolk extender and extender supplemented with 10% LDL. Furthermore, the percentage of membrane-intact frozen-thawed spermatozoa analyzed by the fluorescent staining was significantly higher (p<0.05) in the extender supplemented with 20% LDL (27.4 +/- 6.5%) than in the other groups. In conclusion, 20% LDL can be used to substitute the whole egg yolk as a cryoprotective additive for freezing semen of the collared peccary. PMID- 26679164 TI - miRNA-592 is downregulated and may target LHCGR in polycystic ovary syndrome patients. AB - The polycystic ovary syndrome (PCOS) is an endocrine disorder mainly associated with infertility. Abnormal regulation of relevant genes is required for follicular development in PCOS. In the current study, the expression of serum miRNAs of PCOS patients was explored using miRNA array followed by qRT-PCR assays. The circulating level of miR-592 was significantly down-regulated in PCOS patients in comparison with healthy controls. Furthermore, we found that miR-592 was inversely correlated with the level of luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Computational analysis predicted that miR-592 interacts with the LHCGR mRNA via binding to a site located in the 3'UTR region. Using a luciferase-based reporter assay we found that miR-592 directly targeted the LHCGR. In KGN cell line, miR-592 overexpression inhibited cell viability and the transition of phase G1 to phase S. Knocking down of LHCGR inhibited cell viability and cell cycle progression in KGN cells, and LHCGR co-transfection reversed the inhibitory effect of miR-592. These results shed new light on the diagnosis and treatment of PCOS syndrome. PMID- 26679165 TI - Short-term incubation of bovine placentome sections as a tool to study xenobiotic mechanism of action. AB - Studies on the effects of various factors, including xenobiotics, on the maternal fetal connections in the placenta are restricted by the lack of a simple and inexpensive research model. We used placentomes collected at a slaughterhouse to in vitro study the bovine sections contained integral maternal-fetal connections. The placentomes from cows (n=4/experiment, 120-150 days post coitum) were cut using a razor blade into 60-80 mg sections and incubated in either DMEM/Ham's F 12 or M-199 supplemented with FCS (2%, 5% or 10%), amniotic fluid (AF or inactive AF, 10% or 20%) or both. The sections (n=4/supplement) were incubated for 24 or 48 h in a water bath at 37.5 degrees C in an atmosphere of 5% CO2 and 95% O2. The structure and secretory activity of placentome sections were maintained when incubated in DMEM/Ham's F-12 with 2% FCS and 10% AF. M-199 was less acidified than DMEM/Ham's F-12 during incubation, and thus, this medium was better able to maintain the integrity of the placenta and the secretion of estradiol, progesterone and oxytocin for 48 h. Moreover, we detected a decrease in the expression of placenta-specific 1 (PLAC1) mRNA (an indicator of trophoblast proliferation) and an increase in the levels of keratin 8 (KRT8; a marker of normal placental barrier function) and hypoxia induced factor 1alpha (HIF1alpha; a marker of hypoxia) mRNA. These results indicate the presence of adaptation and repair mechanisms and confirm the biological activity of the placentome sections. We propose the use of placentome sections as an in vitro model to study maternal fetal connections in cows. PMID- 26679167 TI - Neuropeptide Y directly affects ovarian cell proliferation and apoptosis. AB - The effects of neuropeptide Y (NPY; 0, 10, 100 and 1000 ng/mL) on the expression of PCNA, bax and p53 were examined by immunocytochemistry in porcine luteinized granulosa cells. NPY inhibited proliferation as well as promoted apoptosis and accumulation of p53 in the cells. This is the first report to demonstrate the direct action of NPY on ovarian cell proliferation and apoptosis. The results of the study suggest that the effect is mediated by transcription factor p53. PMID- 26679166 TI - Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2alpha in regression of the human corpus luteum. AB - Our objective was to determine the effects of prostaglandin F2alpha (PGF2alpha) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2alpha, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2alpha induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2alpha, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2alpha production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression. PMID- 26679168 TI - Mineotaur: a tool for high-content microscopy screen sharing and visual analytics. AB - High-throughput/high-content microscopy-based screens are powerful tools for functional genomics, yielding intracellular information down to the level of single-cells for thousands of genotypic conditions. However, accessing their data requires specialized knowledge and most often that data is no longer analyzed after initial publication. We describe Mineotaur ( http://www.mineotaur.org ), a open-source, downloadable web application that allows easy online sharing and interactive visualisation of large screen datasets, facilitating their dissemination and further analysis, and enhancing their impact. PMID- 26679170 TI - A response to the SAGES TAVAC assessment of the da Vinci Surgical System. PMID- 26679169 TI - Case report of optic atrophy in Dentatorubropallidoluysian Atrophy (DRPLA). AB - BACKGROUND: Dentatorubropallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease that is associated with numerous movement disorders. Ocular problems also occur with DRPLA with reports of corneal endothelial degeneration in some patients living with the disease. We report a new visual problem associated with DRPLA, optic atrophy. CASE PRESENTATION: A 47 year-old man presented complaining of progressive visual loss associated with optic atrophy on ophthalmological evaluation. He gradually developed a progressive ataxia with dystonia. Brain MRI revealed a diffuse leukoencephalopathy. Genetic analysis revealed 62 CAG repeats in one allele of the DRPLA gene and he was diagnosed with DRPLA. CONCLUSION: Optic atrophy should be included in the clinical spectrum of DRPLA. PMID- 26679171 TI - Effects of reactive oxygen species on the physical properties of polypropylene surgical mesh at various concentrations: a model for inflammatory reaction as a cause for mesh embrittlement and failure. AB - BACKGROUND: Oxidative degradation by reactive oxygen species (ROS) from inflammation initiates cross-linking, depolymerization, and formation of a quasi crystalline quality in polypropylene (PP) meshes that cause embrittlement (J Urol 188:1052, 2012). Embrittlement leads to change in tensile strength and is associated with post-operative complications that include pain, adhesion, dislodgment, and fragmentation. METHODS: A laboratory environment was constructed to study the relationship between concentration of ROS and change in tensile strength. Samples of Ethicon Ultrapro(c) PP mesh were exposed to 1 mM, 0.1 M, or 1 M hydrogen peroxide solutions for 6 months and were subjected to load displacement tensile testing (LDTT) and compared to unexposed (0 M) meshes of the same brand. RESULTS: Load at failure and elongation to failure after LDTT were determined with 95 % confidence interval. For unexposed (0 M) samples, tensile strength was 28.0 +/- 2.4 lbf and elongation to failure was 2.0 +/- 0.3 in. For samples exposed to 1 mM, tensile strength was 19.2 +/- 1.1 lbf and the elongation to failure was 2.0 +/- 0.1 in. For samples exposed to 0.1 M, tensile strength was 19.3 +/- 1.6 lbf and elongation to failure was 1.9 +/- 0.1 in. For samples exposed to 1 M, tensile strength was 20.7 +/- 1.2 lbf and elongation to failure was 0.47 +/- 0.02 in. CONCLUSION: The results demonstrated that a 6-month exposure to a physiologic range of ROS (1 mM) decreased tensile strength of PP mesh by 31 %. 1 mM and 0.1 M samples behaved similarly demonstrating properties of a quasi-crystalline nature. 1 M samples displayed qualities of extreme embrittlement. Scanning electron microscopy (SEM) observed fiber changes. 1 M meshes had features of brittle materials. Knowledge of changes in physical properties of PP meshes is useful for considerations for the development of a more biocompatible surgical mesh. PMID- 26679172 TI - Sodium phosphate versus polyethylene glycol for colonoscopy bowel preparation: an updated meta-analysis of randomized controlled trials. AB - BACKGROUND: Adequate bowel cleansing is of great importance for a high-quality colonoscopy examination. Nevertheless, whether sodium phosphate or polyethylene glycol is a gold standard agent for bowel preparation is still under debate. In consideration of the clinical needs, we thus performed an updated meta-analysis of randomized controlled trials concerning the comparison between both regimens. The efficacy, safety and acceptability of each regimen are major indicators to measure and appraise. METHODS: By searching PubMed, EMBASE, Web of Science and Cochrane Library databases, 15 original trials published from 2000 to 2014 were included as eligible studies. We carried out data extraction and subsequent pooling analysis for each indicator in a standard manner. Sensitivity analysis was performed by elimination of low-quality trials, while a funnel plot and Egger's test were employed to analyze the publication bias across studies. RESULTS: Our pooling analysis revealed that patients undergoing sodium phosphate as a cleansing agent displayed better acceptability, compliance, cleansing scores, preparation taste, polyp detection rate and less adverse effects including nausea, vomiting and abdominal pain (P < 0.05). In terms of procedure time, adequate preparation rate and electrolyte concentration, there was no significant difference between both regimens (P > 0.05). The pooling analysis offered stable conclusions which were verified by our sensitivity analysis. There was no publication bias across studies as a symmetric funnel plot was demonstrated and the result of Egger's test was P = 0.56. CONCLUSIONS: Regarding preparation efficacy, safety and acceptability, sodium phosphate was a better agent than polyethylene glycol for colonoscopy bowel cleansing, with its advantages of higher efficacy, better tolerability and acceptability as well as comparable safety. PMID- 26679173 TI - Acute laparoscopic and open sigmoidectomy for perforated diverticulitis: a propensity score-matched cohort. AB - BACKGROUND: Hartmann's procedure for perforated diverticulitis can be characterised by high morbidity and mortality rates. While the scientific community focuses on laparoscopic lavage as an alternative for laparotomy, the option of laparoscopic sigmoidectomy seems overlooked. We compared morbidity and hospital stay following acute laparoscopic sigmoidectomy (LS) and open sigmoidectomy (OS) for perforated diverticulitis. METHODS: This retrospective cohort parallel to the Ladies trial included patients from 28 Dutch academic or teaching hospitals between July 2010 and July 2014. Patients with LS were matched 1:2 to OS using the propensity score for age, gender, previous laparotomy, CRP level, gastrointestinal surgeon, and Hinchey classification. RESULTS: The propensity-matched cohort consisted of 39 patients with LS and 78 patients with OS, selected from a sample of 307 consecutive patients with purulent or faecal perforated diverticulitis. In both groups, 66 % of the patients had Hartmann's procedure and 34 % had primary anastomosis. The hospital stay was shorter following LS (LS 7 vs OS 9 days; P = 0.016), and the postoperative morbidity rate was lower following LS (LS 44 % vs OS 66 %; P = 0.016). Mortality was low in both groups (LS 3 % vs OS 4 %; P = 0.685). The stoma reversal rate after Hartmann's procedure was higher following laparoscopy, with a probability of being stoma free at 12 months of 88 and 62 % in the laparoscopic and open groups, respectively (P = 0.019). After primary anastomosis, the probability of reversal was 100 % in both groups. CONCLUSIONS: In this propensity score-matched cohort, laparoscopic sigmoidectomy is superior to open sigmoidectomy for perforated diverticulitis with regard to postoperative morbidity and hospital stay. PMID- 26679174 TI - Retrograde laparoscopic resection of left side of the liver: a safe and effective way. AB - OBJECTIVE: The safety and feasibility of retrograde laparoscopic resection of the left side of the liver. METHODS: Ninety-three laparoscopic left hepatic lobe cases were selected between August 2010 and August 2014 from our institution. A retrospective cohort study was performed between the antegrade partial hepatectomy group (47 cases; dissection from the first porta hepatis to the second) and the retrograde partial hepatectomy group (46 cases; dissection from the second porta hepatis to the first), to compare the length of time needed for resection, the amount of bleeding, post-operative time in the hospital, and the incidence of major complications, such as bile leakage, abdominal abscess, and post-hepatectomy hemorrhage. RESULTS: All of the cases had a successful laparoscopic partial hepatectomy without the need for an intraoperative blood transfusion. Patients were able to ambulate on post-operative day 1 and tolerated a liquid diet on post-operative day 1 or 2. There were no statistical differences of post-operative hospital length of stay or incidence of major complications between the two groups. Both duration of resection and the amount of bleeding were less in the retrograde group than of those in the antegrade group, due to the lower incidence of hepatic vein injury in the retrograde group. CONCLUSION: Occlusion of both the inflow and outflow hepatic vessels combined with retrograde hepatectomy from the second porta hepatis to the first, demonstrated less hemorrhage and lower incidence of hepatic veins injury during laparoscopic partial hepatectomy. PMID- 26679175 TI - Preliminary design of an actuated imaging probe for generation of additional visual cues in a robotic surgery. AB - BACKGROUND: The aim of this study was to enhance the visual feedback of surgeons, during robotic surgeries, by designing and developing an actuated 2D imaging probe, which is used in conjunction with the traditional stereoscopic camera of the da Vinci surgical system. The probe provides the surgeon with additional visual cues, overcoming visualization constraints encountered during certain scenarios of robot-assisted minimally invasive surgery. METHODS: The actuated imaging probe is implemented as a master-slave tele-manipulated system, and it is designed to be compatible with the da Vinci surgical system. The detachable probe design enables it to be mounted on any of the EndoWrist((r)) instruments of the robot and is controlled by the surgeon using a custom-made pedal system. The image from the 2D probe is rendered along with the stereoscopic view on the surgeon's console. RESULTS: The experimental results demonstrate the effectiveness of the proposed actuated imaging probe when used as an additional visualization channel and in surgical scenarios presenting visual problems due to tissue occlusion. CONCLUSION: The study shows the potential benefits of an additional actuated imaging probe when used in conjunction with traditional surgical instruments to perform surgical tasks requiring visualization from multiple orientations and workspaces. PMID- 26679176 TI - Clear differences in metabolic and morphological adaptations of akinetes of two Nostocales living in different habitats. AB - Akinetes are resting spore-like cells formed by some heterocyst-forming filamentous cyanobacteria for surviving long periods of unfavourable conditions. We studied the development of akinetes in two model strains of cyanobacterial cell differentiation, the planktonic freshwater Anabaena variabilis ATCC 29413 and the terrestrial or symbiotic Nostoc punctiforme ATCC 29133, in response to low light and phosphate starvation. The best trigger of akinete differentiation of Anabaena variabilis was low light; that of N. punctiforme was phosphate starvation. Light and electron microscopy revealed that akinetes of both species differed from vegetative cells by their larger size, different cell morphology and large number of intracellular granules. Anabaena variabilis akinetes had a multilayer envelope; those of N. punctiforme had a simpler envelope. During akinete development of Anabaena variabilis, the amount of the storage compounds cyanophycin and glycogen increased transiently, whereas in N. punctiforme, cyanophycin and lipid droplets increased transiently. Photosynthesis and respiration decreased during akinete differentiation in both species, and remained at a low level in mature akinetes. The clear differences in the metabolic and morphological adaptations of akinetes of the two species could be related to their different lifestyles. The results pave the way for genetic and functional studies of akinete differentiation in these species. PMID- 26679177 TI - Acute Febrile Illness and Influenza Disease Burden in a Rural Cohort Dedicated to Malaria in Senegal, 2012-2013. AB - BACKGROUND: African populations are considered to be particularly vulnerable to fever illnesses, including malaria, and acute respiratory disease, owing to limited resources and overcrowding. However, the overall burden of influenza in this context is poorly defined and incidence data for African countries are scarce. We therefore studied the fever syndrome incidence and more specifically influenza incidence in a cohort of inhabitants of Dielmo and Ndiop in Sokone district, Senegal. METHODS: Daily febrile-illness data were prospectively obtained from January 2012 to December 2013 from the cohort of the villages of Dielmo and Ndiop, initially dedicated to the study of malaria. Nasopharyngeal swabs were collected from, and malaria diagnosis tests (thick blood smears) carried out on, every febrile individual during clinical visits; reverse transcriptase-polymerase chain reaction was used to identify influenza viruses in the samples. Binomial negative regression analysis was used to study the relationship between the monthly incidence rate and various covariates. RESULTS: In Dielmo and Ndiop, the incidence of malaria has decreased, but fever syndromes remain frequent. Among the 1036 inhabitants included in the cohort, a total of 1,129 episodes of fever were reported. Influenza was present all year round with peaks in October-December 2012 and August 2013. The fever, ILI and influenza incidence density rates differed significantly between age groups. At both sites, the adjusted incidence relative risks for fever syndromes and ILI were significantly higher in the [6-24 months) than other age groups: 7.3 (95%CI: [5.7 9.3]) and 16.1 (95%CI: [11.1-23.3]) respectively. The adjusted incidence relative risk for influenza was significantly higher for the [0-6 months) than other age groups: 9.9 (95%CI: [2.9-33.6]). At both sites, incidence density rates were lowest among adults > = 50 years. CONCLUSIONS: In this rural setting in Senegal, influenza was most frequent among the youngest children. Preventive strategies targeting this population should be implemented. PMID- 26679178 TI - Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis. AB - OBJECTIVES: Cardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD. METHODS: Fifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined. RESULTS: Global systolic function was reduced (EF 51 +/- 10%, HD versus 59 +/- 5%, controls, p < 0.001; PSS 15.9 +/- 3.7% versus 19.5 +/- 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 +/- 0.33s(-1) versus 1.31 +/- 0.38s( 1), p = 0.003). LV mass index was increased (63[54,79]g/m(2) versus 46[42,53]g/m(2), p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity. CONCLUSION: Patients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy. KEY POINTS: * First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients. * Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV. * Reductions in strain localised to the septal and anterior wall. * Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms. * Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes. PMID- 26679179 TI - Iodine concentration as a perfusion surrogate marker in oncology: Further elucidation of the underlying mechanisms using Volume Perfusion CT with 80 kVp. AB - OBJECTIVES: To assess the value of iodine concentration (IC) in computed tomography data acquired with 80 kVp, as a surrogate for perfusion imaging in hepatocellular carcinoma (HCC) and lymphoma by comparing iodine related attenuation (IRA) with quantitative Volume Perfusion CT (VPCT)-parameters. METHODS: VPCT-parameters were compared with intra-tumoral IC at 5 time points after the aortic peak enhancement (APE) with a temporal resolution of 3.5 sec in untreated 30 HCC and 30 lymphoma patients. RESULTS: Intra-tumoral perfusion parameters for HCC showed a blood flow (BF) of 52.7 +/- 17.0 mL/100 mL/min, blood volume (BV) 12.6 +/- 4.3 mL/100 mL, arterial liver perfusion (ALP) 44.4 +/- 12.8 mL/100 mL/min. Lesion IC 7 sec after APE was 133.4 +/- 57.3 mg/100 mL. Lymphoma showed a BF of 36.8 +/- 13.4 mL/100 mL/min, BV of 8.8 +/- 2.8 mL/100 mL and IC of 118.2 +/- 64.5 mg/100 mL 3.5 sec after APE. Strongest correlations exist for VPCT derived BF and ALP with IC in HCC 7 sec after APE (r = 0.71 and r = 0.84) and 3.5 sec after APE in lymphoma lesions (r = 0.77). Significant correlations are also present for BV (r = 0.60 and r = 0.65 for HCC and lymphoma, respectively). CONCLUSIONS: We identified a good, time-dependent agreement between VPCT-derived flow values and IC in HCC and lymphoma. Thus, CT-derived ICs 7 sec after APE in HCC and 3.5 sec in lymphoma may be used as surrogate imaging biomarkers for tumor perfusion with 80 kVp. KEY POINTS: * Iodine concentration derived from low kVp CT is regarded as perfusion surrogate * Correlation with Perfusion CT was performed to elucidate timing and histology dependencies * Highest correlation was present 7 sec after aortic peak enhancement in hepatocellular carcinoma * In lymphoma, highest correlation was calculated 3.5 sec after aortic peak enhancement * With these results, further optimization of Dual energy CT protocols is possible. PMID- 26679181 TI - Erratum to: Navigated MRI-guided liver biopsies in a closed-bore scanner: experience in 52 patients. PMID- 26679180 TI - MRI texture analysis of subchondral bone at the tibial plateau. AB - OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA). METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40 50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly. RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %). CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment. KEY POINTS: * Improved techniques to monitor OA disease progression and treatment response are desirable * Subchondral bone (SB) may play significant role in the development of OA * MRI texture analysis is a method of quantifying changes in SB architecture * Pilot study showed that this technique is feasible and reliable * Significant differences in SB texture were demonstrated between individuals with/without OA. PMID- 26679182 TI - Erratum to: Short- and long-term effects of clinical audits on compliance with procedures in CT scanning. PMID- 26679183 TI - Quantification of early fatty infiltration of the rotator cuff muscles: comparison of multi-echo Dixon with single-voxel MR spectroscopy. AB - OBJECTIVES: To evaluate quantification of early fatty infiltration in supraspinatus muscles with magnetic resonance (MR) imaging using a T2*-corrected multi-echo 3D-gradient-echo Dixon-based sequence (multi-echo Dixon) and compare it to proton-MR-spectroscopy. METHODS: Sixty subjects (mean age 46 years, 41 men) with good supraspinatus muscle quality on 1.5 T MR imaging were included. Fat percentage (FP) in the supraspinatus muscle was quantified using a multi-echo Dixon compared to single-voxel MR spectroscopy as reference standard. In 18 subjects the multi-echo Dixon was repeated to assess test-retest reliability. Measurements based on multi-echo Dixon were performed by two independent readers by placing regions-of-interest (ROIs) in the supraspinatus muscle corresponding to the MR-spectroscopy voxel. Intraclass and concordance correlation coefficients (ICC/CCC) were used for statistical analysis. RESULTS: Test-retest reliability was substantial for reader 1 (ICC = 0.757) and almost perfect for reader 2 (ICC = 0.873). Inter-reader reliability for multi-echo Dixon was almost perfect (ICC = 0.893, P < .0005). Mean FP in all 60 subjects with multi-echo Dixon was 3.5 +/- 1.6 for reader 1, 3.7 +/- 1.8 for reader 2, and 2.8 +/- 1.4 with MR spectroscopy. Correlation between multi-echo Dixon and MR spectroscopy was moderate (CCC = 0.641). CONCLUSION: The multi-echo Dixon sequence is a reliable method and comparable to MR-spectroscopy for quantification of low levels of fatty infiltration in the supraspinatus muscle. KEY POINTS: * Multi-echo Dixon for low fat quantification in muscles is reliable. * Multi-echo Dixon low fat quantification is comparable to single-voxel MR spectroscopy * Multi-echo Dixon detects substantial differences in fatty infiltration within Goutallier 0-1. PMID- 26679184 TI - AHA classification of coronary and carotid atherosclerotic plaques by grating based phase-contrast computed tomography. AB - OBJECTIVES: To evaluate the potential of grating-based phase-contrast computed tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. METHODS: Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. RESULTS: A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were >=0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. CONCLUSIONS: These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. KEY POINTS: * Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. * Phase-contrast CT can detect and differentiate AHA plaque types. * Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. * Overall agreement was higher in carotid than in coronary arteries. PMID- 26679185 TI - Bacterial small RNAs in the Genus Rickettsia. AB - BACKGROUND: Rickettsia species are obligate intracellular Gram-negative pathogenic bacteria and the etiologic agents of diseases such as Rocky Mountain spotted fever (RMSF), Mediterranean spotted fever, epidemic typhus, and murine typhus. Genome sequencing revealed that R. prowazekii has ~25 % non-coding DNA, the majority of which is thought to be either "junk DNA" or pseudogenes resulting from genomic reduction. These characteristics also define other Rickettsia genomes. Bacterial small RNAs, whose biogenesis is predominantly attributed to either the intergenic regions (trans-acting) or to the antisense strand of an open reading frame (cis-acting), are now appreciated to be among the most important post-transcriptional regulators of bacterial virulence and growth. We hypothesize that intergenic regions in rickettsial species encode for small, non coding RNAs (sRNAs) involved in the regulation of its transcriptome, leading to altered virulence and adaptation depending on the host niche. RESULTS: We employed a combination of bioinformatics and in vitro approaches to explore the presence of sRNAs in a number of species within Genus Rickettsia. Using the sRNA Identification Protocol using High-throughput Technology (SIPHT) web interface, we predicted over 1,700 small RNAs present in the intergenic regions of 16 different strains representing 13 rickettsial species. We further characterized novel sRNAs from typhus (R. prowazekii and R. typhi) and spotted fever (R. rickettsii and R. conorii) groups for their promoters and Rho-independent terminators using Bacterial Promoter Prediction Program (BPROM) and TransTermHP prediction algorithms, respectively. Strong sigma70 promoters were predicted upstream of all novel small RNAs, indicating the potential for transcriptional activity. Next, we infected human microvascular endothelial cells (HMECs) with R. prowazekii for 3 h and 24 h and performed Next Generation Sequencing to experimentally validate the expression of 26 sRNA candidates predicted in R. prowazekii. Reverse transcriptase PCR was also used to further verify the expression of six putative novel sRNA candidates in R. prowazekii. CONCLUSIONS: Our results yield clear evidence for the expression of novel R. prowazekii sRNA candidates during infection of HMECs. This is the first description of novel small RNAs for a highly pathogenic species of Rickettsia, which should lead to new insights into rickettsial virulence and adaptation mechanisms. PMID- 26679187 TI - Study on Equity and Efficiency of Health Resources and Services Based on Key Indicators in China. AB - BACKGROUND: This study aims to evaluate the dialectical relationship between equity and efficiency of health resource allocation and health service utilization in China. METHODS: We analyzed the inequity of health resource allocation and health service utilization based on concentration index (CI) and Gini coefficient. Data envelopment analysis (DEA) was used to evaluate the inefficiency of resource allocation and service utilization. Factor Analysis (FA) was used to determine input/output indicators. RESULTS: The CI of Health Institutions, Beds in Health Institutions, Health Professionals and Outpatient Visits were -0.116, -0.012, 0.038, and 0.111, respectively. Gini coefficient for the 31 provinces varied between 0.05 and 0.43; out of these 23 (742%) were observed to be technically efficient constituting the "best practice frontier". The other 8 (25.8%) provinces were technically inefficient. CONCLUSIONS: Health professionals and outpatient services are focused on higher income levels, while the Health Institutions and Beds in Health Institutions were concentrated on lower income levels. In China, a few provinces attained a basic balance in both equity and efficiency in terms of current health resource and service utilization, thus serving as a reference standard for other provinces. PMID- 26679186 TI - The EPIC Kids Study: a randomized family-focused YMCA-based intervention to prevent type 2 diabetes in at-risk youth. AB - BACKGROUND: It is well established that behavioral lifestyle interventions resulting in modest weight reduction in adults can prevent or delay type 2 diabetes mellitus; however in children, successful weight management interventions are rarely found outside of controlled clinical settings. The lack of effective community-based programs is a barrier to reducing obesity prevalence and diabetes risk in children. The objective of our study is to develop and test a group-randomized family-centered community-based type 2 diabetes prevention intervention targeting at-risk children, 9- to 12-years-old. METHODS/DESIGN: Using participatory methods, the adult-focused YMCA Diabetes Prevention Program was adapted for families, creating a novel lifestyle behavior change program focused on healthy eating, physical activity, and a supportive home environment. The program will be tested in sixty 9- to 12-year-old children at risk of diabetes and sixty parents over 12 consecutive weeks with two intervention formats randomized by location: a face-to-face instructor-led program, or a hybrid program with alternating face-to-face and mobile technology-delivered content. Anthropometric, behavioral, psychosocial and physiological outcomes will be assessed at baseline, post-intervention (12 weeks), and follow-up (24 weeks). Secondary outcomes are participant acceptability, feasibility, and adherence. The RE-AIM framework (reach, efficacy, adoption, implementation, and maintenance) will guide intervention implementation and evaluation. Changes at 12 weeks will be assessed using a paired t-test combining both delivery formats. Exploratory models using linear regression analysis will estimate the magnitude of the difference between the face-to-face and hybrid format. The sample size of 60 children, informed by a previous YMCA intervention in which -4.3 % change in overweight (SE = 1.1) was observed over 6 months, will give us 80 % power to detect an effect size of this magnitude, assuming a one-sided test at alpha = 0.05. DISCUSSION: The proposed study capitalizes on a partnership with the YMCA, a popular and widespread community organization, and uses mobile technologies to extend program reach while potentially reducing burden associated with weekly attendance. The long-term goal is to create a scalable, replicable, and sustainable pediatric "diabesity" prevention program that overcomes existing barriers to the translation of efficacious interventions into effective community programs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02421198 on April 15, 2015. PMID- 26679188 TI - Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan. AB - BACKGROUND: Proportional mortality ratio data indicate that healthcare workers (HCWs) have an elevated tuberculosis (TB) mortality. Whether this is caused by an increased TB incidence, a worse TB treatment outcome, or a combination of effects, remains unclear. To elucidate the hazard components of occupational TB, we assessed TB incidence and TB treatment outcome among HCWs in Taiwan. METHODS: We compared the incidence of active TB among HCWs at a major medical center in Taiwan with that of Taiwan general population in 2004-2012. We also compared the TB treatment outcome of HCWs with that of age/sex-matched non-HCW patients treated at the same hospital, as well as that of nationally registered TB patients. RESULTS: The standardized TB incidence ratio of the HCWs was 1.9 (95% confidence interval [CI]: 1.2-2.9), compared with the general population. HCWs with pulmonary TB (n = 30) were less likely to have underlying diseases, delay in diagnosis, delay in treatment, or side effects of treatment, compared with age/sex-matched non-HCW TB patients (n = 120) (all Ps<0.05). The TB treatment outcome of HCWs was significantly better than that of non-HCW patients (TB related mortality: 0.0% vs. 5.8%, P = 0.008, Mantel-Haenszel test). The standardized TB-related mortality rate was 1.08% [95% CI: 0.96% - 1.20%] for all of the nationally registered TB patients in Taiwan. CONCLUSIONS: HCWs are at increased risk of active TB, compared with general population. To mitigate this occupational hazard, more efforts need to be directed towards the prevention of nosocomial TB transmission. Healthy worker effect, more rapid diagnosis, and less delay in treatment contribute to a lower TB-related mortality in HCWs. PMID- 26679189 TI - Horizontal nystagmus and multiple sclerosis using 3-Tesla magnetic resonance imaging. AB - BACKGROUND: Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio. OBJECTIVE: We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI. METHODS: Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography. RESULTS: Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006). CONCLUSION: In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS. PMID- 26679190 TI - "With a Little Help from My Friends"-Social Motility in Trypanosoma brucei. PMID- 26679191 TI - Exploring Change Processes in School-Based Mentoring for Bullied Children. AB - We examined change processes associated with the school-based, lunchtime mentoring of bullied children. We used data from a one-semester open trial of Lunch Buddy (LB) mentoring (N = 24) to examine changes in bullied children's lunchtime peer relationships. We also tested whether these changes predicted key outcomes (i.e., peer victimization, social preference) post-mentoring. Results provided partial support that bullied children paired with LB mentors experienced improved lunchtime peer relationships and that gains in lunchtime relationships predicted post-mentoring levels of social preference and peer victimization. Neither child nor mentors' ratings of the mentoring relationship predicted post mentoring outcomes; however, child-rated mentor support and conflict predicted improvements in lunchtime peer relationships. We discuss implications for future research on school-based mentoring as a form of selective intervention for bullied children. PMID- 26679192 TI - Learning Control Over Emotion Networks Through Connectivity-Based Neurofeedback. AB - Most mental functions are associated with dynamic interactions within functional brain networks. Thus, training individuals to alter functional brain networks might provide novel and powerful means to improve cognitive performance and emotions. Using a novel connectivity-neurofeedback approach based on functional magnetic resonance imaging (fMRI), we show for the first time that participants can learn to change functional brain networks. Specifically, we taught participants control over a key component of the emotion regulation network, in that they learned to increase top-down connectivity from the dorsomedial prefrontal cortex, which is involved in cognitive control, onto the amygdala, which is involved in emotion processing. After training, participants successfully self-regulated the top-down connectivity between these brain areas even without neurofeedback, and this was associated with concomitant increases in subjective valence ratings of emotional stimuli of the participants. Connectivity based neurofeedback goes beyond previous neurofeedback approaches, which were limited to training localized activity within a brain region. It allows to noninvasively and nonpharmacologically change interconnected functional brain networks directly, thereby resulting in specific behavioral changes. Our results demonstrate that connectivity-based neurofeedback training of emotion regulation networks enhances emotion regulation capabilities. This approach can potentially lead to powerful therapeutic emotion regulation protocols for neuropsychiatric disorders. PMID- 26679193 TI - Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks. AB - Isolated focal dystonias are a group of disorders with diverse symptomatology but unknown pathophysiology. Although recent neuroimaging studies demonstrated regional changes in brain connectivity, it remains unclear whether focal dystonia may be considered a disorder of abnormal networks. We examined topology as well as the global and local features of large-scale functional brain networks across different forms of isolated focal dystonia, including patients with task-specific (TSD) and nontask-specific (NTSD) dystonias. Compared with healthy participants, all patients showed altered network architecture characterized by abnormal expansion or shrinkage of neural communities, such as breakdown of basal ganglia cerebellar community, loss of a pivotal region of information transfer (hub) in the premotor cortex, and pronounced connectivity reduction within the sensorimotor and frontoparietal regions. TSD were further characterized by significant connectivity changes in the primary sensorimotor and inferior parietal cortices and abnormal hub formation in insula and superior temporal cortex, whereas NTSD exhibited abnormal strength and number of regional connections. We suggest that isolated focal dystonias likely represent a disorder of large-scale functional networks, where abnormal regional interactions contribute to network-wide functional alterations and may underline the pathophysiology of isolated focal dystonia. Distinct symptomatology in TSD and NTSD may be linked to disorder-specific network aberrations. PMID- 26679195 TI - YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis. AB - Yes-associated protein (YAP) is a key transcriptional cofactor of the Hippo pathway, critical for the development of multiple organs. However, its role in the developing brain remains poorly understood. Here, we found that YAP was highly expressed in astrocytes and YAP deletion elevated the astrocytic activation in culture and in vivo, which was associated with microglial activation. At the molecular level, YAP in astrocytes was activated by IFNbeta or ciliary neurotrophic factor (CNTF), which was necessary for IFNbeta or CNTF induction of the suppressor of cytokine signaling 3 (SOCS3), a negative regulator of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory pathway. YAP(-/-) astrocytes thus showed hyperactivation of the JAK STAT inflammatory pathway and reactive astrogliosis. Expression of SOCS3 in YAP( /-) astrocytes prevented the hyperactivation of STAT3 and partially restored the astrocytic activation. Finally, reactive astrogliosis was associated with blood brain barrier dysfunction in YAP brain-selective knockout mice. Taken together, these results identify unrecognized functions of YAP in preventing reactive astrogliosis and reveal a pathway of YAP-SOCS for the negatively control of neuroinflammation. PMID- 26679194 TI - Serotonin Transporter Genetic Variation is Differentially Associated with Reflexive- and Reflective-Optimal Learning. AB - Learning to respond optimally under a broad array of environmental conditions is a critical brain function that requires engaging the cognitive systems that are optimal for solving the task at hand. Serotonin is implicated in learning and decision-making, but the specific functions of serotonin in system-level cognitive control remain unclear. Across 3 studies, we examined the influence of a polymorphism within the promoter region of the serotonin transporter gene (5 HTTLPR polymorphism in SLC6A4) on participants' ability to engage the task appropriate cognitive system when the reflexive (Experiments 1 and 2) or the reflective (Experiment 3) system was optimal. Critically, we utilized a learning task for which all aspects remain fixed with only the nature of the optimal cognitive processing system varying across experiments. Using large community samples, Experiments 1 and 2 (screened for psychiatric diagnosis) found that 5 HTTLPR S/LG allele homozygotes, with putatively lower serotonin transport functionality, outperformed LA allele homozygotes in a reflexive-optimal learning task. Experiment 3 used a large community sample, also screened for psychiatric diagnosis, and found that 5-HTTLPR LA homozygotes, with putatively higher serotonin transport functionality, outperformed S/LG allele homozygotes in a reflective-optimal learning task. PMID- 26679196 TI - The effect of particle shape and size on cellular uptake. AB - Particle shape and size have been well-recognized to exhibit important effect on drug delivery and as an excellent candidate for drug delivery applications. The recent advances in the "top-down" and "bottom-up" approaches make it possible to develop different shaped and sized polymeric nanostructures, which provide a chance to tailor the shape of the nanostructures as a drug carrier. Presently, a large amount of cellular uptake data is available for particle shape and size effect on drug delivery. However, the effect has not been well formulated or described quantitatively. In the present paper, the dynamic process of the effects of particle shape and size on cellular uptake is analyzed, quantitative expression for the influence of particle shape and size on cellular uptake is proposed on the basis of local geometric feature of particle shape and diffusion approach of a particle in a medium rationally, and the relevant parameters in the formulation are determined by the available test data. The results indicate the validity of the present formulations. PMID- 26679197 TI - ASSESSMENT OF MAST IN EUROPEAN PATIENT-CENTERED TELEMEDICINE PILOTS. AB - OBJECTIVES: Model for ASsessment of Telemedicine Applications (MAST) is a health technology assessment (HTA) inspired framework for assessing the effectiveness and contribution to quality of telemedicine applications based on rigorous, scientific data. This study reports from a study of how it was used and perceived in twenty-one pilots of the European project RENEWING HEALTH (RH). The objectives of RH were to implement large-scale, real-life test beds for the validation and subsequent evaluation of innovative patient-centered telemedicine services. The study is a contribution to the appraisal of HTA methods. METHODS: A questionnaire was administered for project leaders of the pilots. It included questions about use and usefulness of MAST for (i) preceding considerations, (ii) evaluation of outcomes within seven domains, and (iii) considerations of transferability. Free text spaces allowed for proposals of improvement. The responses covered all pilots. A quantitative summary of use and a qualitative analysis of usefulness were performed. RESULTS: MAST was used and considered useful for pilot evaluations. Challenges included problems to scientifically determine alternative service options and outcome within the seven domains. Proposals for improvement included process studies and adding domains of technological usability, responsible innovation, health literacy, behavior change, caregiver perspectives and motivational issues of professionals. CONCLUSIONS: MAST was used according to its structure. Its usefulness in patient centered pilots can be improved by adding new stakeholder groups. Interdependencies between scientific rigor, resources and timeliness should be addressed. Operational options for improvements include process studies, literature reviews and sequential mini-HTAs for identification of areas for more elaborate investigations. PMID- 26679198 TI - Built-In Potential in Fe2O3-Cr2O3 Superlattices for Improved Photoexcited Carrier Separation. AB - Hematite (alpha-Fe2 O3) is engineered to improve photoexcited electron-hole pair separation by synthesizing Fe2O3-Cr2O3 superlattices (SLs) with precise atomic control. The different surface terminations exhibited by Fe2O3 and Cr2O3 determine the hetero-junction interface structure and result in controllable, noncommutative band offset values. This controllable band alignment is harnessed to generate a built-in potential as large as 0.8 eV in Fe2 O3-Cr2O3 SLs. PMID- 26679199 TI - A computational method for drug repositioning using publicly available gene expression data. AB - MOTIVATION: The identification of new therapeutic uses of existing drugs, or drug repositioning, offers the possibility of faster drug development, reduced risk, lesser cost and shorter paths to approval. The advent of high throughput microarray technology has enabled comprehensive monitoring of transcriptional response associated with various disease states and drug treatments. This data can be used to characterize disease and drug effects and thereby give a measure of the association between a given drug and a disease. Several computational methods have been proposed in the literature that make use of publicly available transcriptional data to reposition drugs against diseases. METHOD: In this work, we carry out a data mining process using publicly available gene expression data sets associated with a few diseases and drugs, to identify the existing drugs that can be used to treat genes causing lung cancer and breast cancer. RESULTS: Three strong candidates for repurposing have been identified- Letrozole and GDC 0941 against lung cancer, and Ribavirin against breast cancer. Letrozole and GDC 0941 are drugs currently used in breast cancer treatment and Ribavirin is used in the treatment of Hepatitis C. PMID- 26679200 TI - Effects of polyphosphates and fluoride on hydroxyapatite dissolution: A pH-stat investigation. AB - OBJECTIVES: This study investigated the immediate and sustained effect of sodium trimetaphosphate (TMP) and sodium hexametaphosphate (HMP) associated or not with fluoride (F) on hydroxyapatite (HA) dissolution using an erosion-like model, considering as well as the influence of salivary coating. DESIGN: Baseline dissolution rates were determined for HA discs using a pH-stat system. In the first set of experiments, HA discs were treated with 1100MUgF/mL, 1% or 8% of HMP, 1% or 8% of TMP and 1100MUgF/mL associated with 1% or 8% of HMP or TMP, totaling 9 groups (n=8). In a second phase, HA discs were kept in pooled human saliva at 37 degrees C for 2h before treatment with deionised water and 1100MUgF/mL associated with 1% or 8% of HMP or TMP, totaling 5 groups (n=8). The post-treatment dissolution rate was determined from three consecutive 30-min assays. Data were analysed using 2 and 3-way ANOVA followed by Fisher and Holm Sidak methods, respectively (alpha=0.05). RESULTS: All test solutions promoted reduction in HA dissolution rate when compared to baseline control in the first post-treatment run (p<0.001). However, a synergistic effect was only observed between fluoride and 1% HMP. Moreover, the duration of inhibitory effect was greater when 8% HMP and 1 or 8% HMP associated with F were assessed (p<0.001). The presence of salivary coating led to higher protection for all groups when compared to discs without coating (p<0.001). CONCLUSION: The reduction of HA dissolution rate, as well as the duration of this effect were influenced by fluoride, type and concentration of phosphate salt and the presence of a salivary coating. PMID- 26679201 TI - Interaction of Candida albicans with periodontal ligament fibroblasts limits biofilm formation over elastomer silicone disks. AB - OBJECTIVE: Candida albicans is the most numerous commensal and potentially pathological yeast in the human oral cavity. The purpose herein is to investigate the ability of C. albicans to form a biofilm in the presence of periodontal ligament (PDL) fibroblasts. MATERIAL AND METHODS: Silicone elastomer disks (SE) were transferred to wells containing PDL cells. C. albicans suspension was added to each well. The whole mixed culture was then allowed to form a biofilm for 48h. Biofilms were quantified by tetrazolium-salt-based (2,3-bis(2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenyl amino) carbonyl]- 2H-tetrazolium hydroxide (XTT). Furthermore, biofilm was visualized by confocal scanning laser and scanning electron microscopy. Migration of C. albicans and its ability to form biofilms in presence of PDL cells was determined by using a transwell system. Last, elutes obtained from co-culturing C. albicans and PDL cells were added to SE disks and covered with C. albicans. The culture plate was then incubated to allow biofilm formation. Biofilms formed over SE disks were quantified using XTT. RESULTS: PDL cells significantly limited the biofilm formation at incubation interval of 48h. PDL cells induced less biofilm compared to mature and thick hyphae in the absence of PDL cells as seen in confocal scanning laser and scanning electron microscopy. The presence of PDL cells limited the migration and formation of biofilm by C. albicans. Elutes obtained from co-culturing PDL cells with C. albicans for one hour induced significantly less biofilm. CONCLUSIONS: This is the first study to report that PDL cells exhibit antifungal activity. While the exact mechanism of how PDL cells limited biofilm formation is yet unknown, it was clear that competent PDL cells promote resistance to C. albicans biofilm formation. PMID- 26679202 TI - Congenital Absence of the Left Ventricular Outflow Tract. PMID- 26679203 TI - Sonographic Evaluation of Diaphragmatic Excursion and Thickness in Healthy Infants and Children. AB - OBJECTIVES: M-mode sonography is a noninvasive method for detection of diaphragmatic excursion and thickness. A few studies have assessed diaphragmatic kinetics in children with diaphragmatic paresis and paralysis, but to our knowledge, no data about normal values in pediatrics are available. The aims of this study were to determine reference values for diaphragmatic excursion and thickness, as evaluated by sonography in healthy infants and children, and identify correlations between them and anthropometric measurements, age, and sex. METHODS: A total of 400 healthy participants aged between 1 month and 16 years, divided into 4 equal groups (group 1, 1 month-2 years; group 2, 2-6 years; group 3, 6-12 years); and group 4, 12-16 years) were studied. M-mode sonography was used to measure the excursion and thickness of the right and left hemidiaphragms (using the liver and spleen as acoustic windows, respectively). RESULTS: Reference values for diaphragmatic excursion and thickness were determined in different age groups of healthy infants and children. There were no significant differences with respect to sex. Significant positive correlations were found between excursion of the right hemidiaphragm and body weight in all age groups (r = 0.52, 0.25, 0.27. and 0.20; P < .001, .013, .011, and .047 for groups 1-4, respectively). We plotted percentile curves for right diaphragmatic excursion against body weight. CONCLUSIONS: This study provides reference values for diaphragmatic excursion and thickness in healthy infants and children. Percentile curves for right diaphragmatic excursion plotted against body weight were plotted. PMID- 26679204 TI - Language of Transducer Manipulation: Codifying Terms for Effective Teaching. AB - There is a need for consistent, repetitive, and reliable terminology to describe the basic manipulations of the ultrasound transducer. Previously, 5 basic transducer motions have been defined and used in education. However, even with this effort, there is still a lack of consistency and clarity in describing transducer manipulation and motion. In this technical innovation, we describe an expanded definition of transducer motions, which include movements to change the transducer's angle of insonation to the target as well as the location on the body to optimize the ultrasound image. This new terminology may allow for consistent teaching and improved communication in the process of image acquisition. PMID- 26679205 TI - Application of Quasistatic Ultrasound Elastography for Examination of Scrotal Lesions. AB - OBJECTIVES: The aims of this study were to investigate the value of applying quasistatic ultrasound elastography for examination of scrotal lesions, to investigate the features of normal testes on quasistatic elastography, and to establish whether testicular and epididymal lesions had specific quasistatic elastographic features. METHODS: We screened 1073 patients who underwent color Doppler sonographic examinations of the testes and epididymides in our hospital and performed quasistatic elastography to evaluate their sonographic features. Measurement data were expressed as mean +/- SD. For intergroup comparisons, we used paired t tests and independent-samples t tests, with P < .05 considered significant. RESULTS: Quasistatic elastography did not reveal any testicular or epididymal abnormalities in 625 cases. Seven cases showed testicular torsion; 3 cases showed testicular space-occupying lesions (1 case each of a testicular teratoma, testicular seminoma, and testicular endodermal sinus tumor); 176 cases showed epididymal lesions (138 cases of caudal epididymal inflammatory masses, 37 cases of caput epididymal cysts, and 1 case of an epididymal lymphangioma); and 262 cases showed varicocele. The normal testicular elastographic appearance showed a 3-ring structure: red surrounding bands with a blue edge region and a green central area. The stiffness in cases of testicular torsion, testicular space-occupying lesions, and epididymal lesions was increased, whereas caput epididymal cysts of different diameters appeared either as green, blue-green-red, or "scooped out." Elastographic results for patients with varicocele were not different from those for normal testes. CONCLUSIONS: Quasistatic elastography can reflect the relative stiffness of the testis and its surrounding tissues, thus providing a novel, reliable, convenient, and noninvasive method for clinical detection of testicular stiffness and related pathologic changes. PMID- 26679206 TI - A tale of two plasticities: leaf hydraulic conductances and related traits diverge for two tropical epiphytes from contrasting light environments. AB - We compared the effects of different light environments on leaf hydraulic conductance (Kleaf ) for two congeneric epiphytes, the tank bromeliads Guzmania lingulata (L.) Mez and Guzmania monostachia (L.) Rusby ex Mez. They occur sympatrically at the study site, although G. monostachia is both wider ranging and typically found in higher light. We collected plants from two levels of irradiance and measured Kleaf as well as related morphological and anatomical traits. Leaf xylem conductance (Kxy ) was estimated from tracheid dimensions, and leaf conductance outside the xylem (Kox ) was derived from a leaky cable model. For G. monostachia, but not for G. lingulata, Kleaf and Kxy were significantly higher in high light conditions. Under both light conditions, Kxy and Kox were co limiting for the two species, and all conductances were in the low range for angiosperms. With respect to hydraulic conductances and a number of related anatomical traits, G. monostachia exhibited greater plasticity than did G. lingulata, which responded to high light chiefly by reducing leaf size. The positive plasticity of leaf hydraulic traits in varying light environments in G. monostachia contrasted with negative plasticity in leaf size for G. lingulata, suggesting that G. monostachia may be better able to respond to forest conditions that are likely to be warmer and more disturbed in the future. PMID- 26679207 TI - Cytomegalovirus colitis in a patient with pemphigus vulgaris. PMID- 26679208 TI - In Response to: Incidence of Exercise-Associated Hyponatremia and Its Association With Nonosmotic Stimuli of Arginine Vasopressin in the GNW100s Ultraendurance Marathon. PMID- 26679209 TI - In Response to: Detecting Impairment Postconcussion Using Reliable Change Indices. PMID- 26679210 TI - In Response to: Sport-Related Concussion Reporting and State Legislative Effects. PMID- 26679211 TI - Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta. AB - BACKGROUND: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. CONCLUSION: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated. PMID- 26679212 TI - Nickel-Catalyzed Borylation of Benzylic Ammonium Salts: Stereospecific Synthesis of Enantioenriched Benzylic Boronates. AB - We have developed a stereospecific, nickel-catalyzed cross-coupling of secondary benzylic ammonium salts and diboronate esters to deliver highly enantioenriched benzylic boronates. This reaction utilizes amine-derived electrophiles, which are readily available in high enantiopurity, and simple, inexpensive nickel catalysts. This reaction has broad scope, enabling synthesis of a variety of secondary benzylic boronates in good yields and excellent ee's. PMID- 26679213 TI - Unconscious Familiarity-based Color-Form Binding: Evidence from Visual Extinction. AB - There is good evidence that early visual processing involves the coding of different features in independent brain regions. A major question, then, is how we see the world in an integrated manner, in which the different features are "bound" together. A standard account of this has been that feature binding depends on attention to the stimulus, which enables only the relevant features to be linked together [Treisman, A., & Gelade, G. A feature-integration theory of attention. Cognitive Psychology, 12, 97-136, 1980]. Here we test this influential idea by examining whether, in patients showing visual extinction, the processing of otherwise unconscious (extinguished) stimuli is modulated by presenting objects in their correct (familiar) color. Correctly colored objects showed reduced extinction when they had a learned color, and this color matched across the ipsi- and contralesional items (red strawberry + red tomato). In contrast, there was no reduction in extinction under the same conditions when the stimuli were colored incorrectly (blue strawberry + blue tomato; Experiment 1). The result was not due to the speeded identification of a correctly colored ipsilesional item, as there was no benefit from having correctly colored objects in different colors (red strawberry + yellow lemon; Experiment 2). There was also no benefit to extinction from presenting the correct colors in the background of each item (Experiment 3). The data suggest that learned color-form binding can reduce extinction even when color is irrelevant for the task. The result is consistent with preattentive binding of color and shape for familiar stimuli. PMID- 26679215 TI - Role of Oculoproprioception in Coding the Locus of Attention. AB - The most common neural representations for spatial attention encode locations retinotopically, relative to center of gaze. To keep track of visual objects across saccades or to orient toward sounds, retinotopic representations must be combined with information about the rotation of one's own eyes in the orbits. Although gaze input is critical for a correct allocation of attention, the source of this input has so far remained unidentified. Two main signals are available: corollary discharge (copy of oculomotor command) and oculoproprioception (feedback from extraocular muscles). Here we asked whether the oculoproprioceptive signal relayed from the somatosensory cortex contributes to coding the locus of attention. We used continuous theta burst stimulation (cTBS) over a human oculoproprioceptive area in the postcentral gyrus (S1EYE). S1EYE cTBS reduces proprioceptive processing, causing ~1 degrees underestimation of gaze angle. Participants discriminated visual targets whose location was cued in a nonvisual modality. Throughout the visual space, S1EYE-cTBS shifted the locus of attention away from the cue by ~1 degrees , in the same direction and by the same magnitude as the oculoproprioceptive bias. This systematic shift cannot be attributed to visual mislocalization. Accuracy of open-loop pointing to the same visual targets, a function thought to rely mainly on the corollary discharge, was unchanged. We argue that oculoproprioception is selective for attention maps. By identifying a potential substrate for the coupling between eye and attention, this study contributes to the theoretical models for spatial attention. PMID- 26679214 TI - Modulation of Frontoparietal Neurovascular Dynamics in Working Memory. AB - Our perception of the world is represented in widespread, overlapping, and interactive neuronal networks of the cerebral cortex. A majority of physiological studies on the subject have focused on oscillatory synchrony as the binding mechanism for representation and transmission of neural information. Little is known, however, about the stability of that synchrony during prolonged cognitive operations that span more than just a few seconds. The present research, in primates, investigated the dynamic patterns of oscillatory synchrony by two complementary recording methods, surface field potentials (SFPs) and near infrared spectroscopy (NIRS). The signals were first recorded during the resting state to examine intrinsic functional connectivity. The temporal modulation of coactivation was then examined on both signals during performance of working memory (WM) tasks with long delays (memory retention epochs). In both signals, the peristimulus period exhibited characteristic features in frontal and parietal regions. Examination of SFP signals over delays lasting tens of seconds, however, revealed alternations of synchronization and desynchronization. These alternations occurred within the same frequency bands observed in the peristimulus epoch, without a specific correspondence between any definite cognitive process (e.g., WM) and synchrony within a given frequency band. What emerged instead was a correlation between the degree of SFP signal fragmentation (in time, frequency, and brain space) and the complexity and efficiency of the task being performed. In other words, the incidence and extent of SFP transitions between synchronization and desynchronization-rather than the absolute degree of synchrony-augmented in correct task performance compared with incorrect performance or in a control task without WM demand. An opposite relationship was found in NIRS: increasing task complexity induced more uniform, rather than fragmented, NIRS coactivations. These findings indicate that the particular features of neural oscillations cannot be linearly mapped to cognitive functions. Rather, information and the cognitive operations performed on it are primarily reflected in their modulations over time. The increased complexity and fragmentation of electrical frequencies in WM may reflect the activation of hierarchically diverse cognits (cognitive networks) in that condition. Conversely, the homogeneity in coherence of NIRS responses may reflect the cumulative vascular reactions that accompany that neuroelectrical proliferation of frequencies and the longer time constant of the NIRS signal. These findings are directly relevant to the mechanisms mediating cognitive processes and to physiologically based interpretations of functional brain imaging. PMID- 26679217 TI - Enhanced Neural Processing of Goal-directed Actions After Active Training in 4 Month-Old Infants. AB - The current study explores the neural correlates of action perception and its relation to infants' active experience performing goal-directed actions. Study 1 provided active training with sticky mittens that enables grasping and object manipulation in prereaching 4-month-olds. After training, EEG was recorded while infants observed images of hands grasping toward (congruent) or away from (incongruent) objects. We demonstrate that brief active training facilitates social perception as indexed by larger amplitude of the P400 ERP component to congruent compared with incongruent trials. Study 2 presented 4-month-old infants with passive training in which they observed an experimenter perform goal directed reaching actions, followed by an identical ERP session to that used in Study 1. The second study did not demonstrate any differentiation between congruent and incongruent trials. These results suggest that (1) active experience alters the brains' response to goal-directed actions performed by others and (2) visual exposure alone is not sufficient in developing the neural networks subserving goal processing during action observation in infancy. PMID- 26679216 TI - Semantics of the Visual Environment Encoded in Parahippocampal Cortex. AB - Semantic representations capture the statistics of experience and store this information in memory. A fundamental component of this memory system is knowledge of the visual environment, including knowledge of objects and their associations. Visual semantic information underlies a range of behaviors, from perceptual categorization to cognitive processes such as language and reasoning. Here we examine the neuroanatomic system that encodes visual semantics. Across three experiments, we found converging evidence indicating that knowledge of verbally mediated visual concepts relies on information encoded in a region of the ventral medial temporal lobe centered on parahippocampal cortex. In an fMRI study, this region was strongly engaged by the processing of concepts relying on visual knowledge but not by concepts relying on other sensory modalities. In a study of patients with the semantic variant of primary progressive aphasia (semantic dementia), atrophy that encompassed this region was associated with a specific impairment in verbally mediated visual semantic knowledge. Finally, in a structural study of healthy adults from the fMRI experiment, gray matter density in this region related to individual variability in the processing of visual concepts. The anatomic location of these findings aligns with recent work linking the ventral-medial temporal lobe with high-level visual representation, contextual associations, and reasoning through imagination. Together, this work suggests a critical role for parahippocampal cortex in linking the visual environment with knowledge systems in the human brain. PMID- 26679218 TI - Serotonin toxicity caused by the interaction of fentanyl and serotonergic medications. PMID- 26679219 TI - An unexpected Bromolactamization of Olefinic Amides Using a Three-Component Co catalyst System. AB - Reaction between (N,N-dimethylamino)pyridine and isocyanate unexpectedly produced a three-component mixture. By using this mixture as an unprecedented three component catalyst system, a facile and selective bromolactamization of olefinic amides has been developed. The protocol confers enhanced selectivity of N- over O cyclization, leading to the formation of a structurally diverse range of lactams including both small and medium ring sizes. PMID- 26679220 TI - Saturated hydrocarbon content in olive fruits and crude olive pomace oils. AB - Olive fruits contain an n-alkane series of saturated hydrocarbons mainly in the pulp. Lower amounts of a complex mixture of paraffins, unresolved by gas chromatography (UCM--unresolved complex mixture), have been found in cuticle, stone (woody shell and seed), olive leaves, and talc used as an aid to olive oil extraction. The amounts of both kinds of hydrocarbons are related to the olive cultivar and are transferred to oils in a proportion depending on the oil obtaining process (centrifugation or solvent extraction). In olive oil obtained by centrifugation, only n-alkanes were detected. However, in olive oil extracted by second centrifugation, small amounts of UCM paraffins were detected together with the n-alkanes. Olive pomace oils showed a very variable content of both types of hydrocarbons according to the different obtaining process, such as double centrifugation, solvent extraction or centrifugation followed by solvent extraction. 'White mineral oil' used in oil extraction machinery is the source of the high concentrations of UCM paraffins found in some olive and olive pomace oils. In the case of second centrifugation olive oil, a maximum limit of 50 mg kg(-1) of UCM is suggested, whereas in the case of crude olive pomace oil, it amounts to 250 mg kg(-1) plus an additional minimum of 1.0 for the n-alkanes/UCM ratio. PMID- 26679221 TI - Influence of soil cover and N and K fertilization on the quality of biofortified QPM in the humid tropics. AB - BACKGROUND: In the humid tropics, unfavorable conditions present challenges to smallholder farmers attempting to meet food demands. The objective of this study was to evaluate the influence of alley cropping and addition of potassium and nitrogen on the productivity and nutritional value of quality protein maize (QPM). The experimental design consisted of randomized blocks with four replicates in a 5 * 2 factorial scheme, with five treatments, Gliricidia + Acacia (GA), Gliricidia + Clitoria (GC), Leucaena + Acacia (LA), Leucaena + Clitoria (LC) and bare soil (BS), in two cropping systems, one with addition of nitrogen and potassium (NK) and one without. RESULTS: The grain yield of LC + NK was significantly higher than that of all other treatments except GC + NK and LA + NK, and six times higher than that of BS + NK. The protein content of LC + NK was higher than that of the treatments without residue. CONCLUSION: Although the mulching of tree legumes increased the yield and quality of food for smallholder agriculture, achieving this outcome requires eliminating potentially negative interactions when combining trees and crops in addition to enhancing the availability and uptake of nutrients. (c) 2015 Society of Chemical Industry. PMID- 26679223 TI - The synthesis and characterization of 1 1 1 1 type diluted ferromagnetic semiconductor (La(1-x)Ca(x))(Zn(1-x) Mn(x))AsO. AB - We report the synthesis and characterization of a bulk form diluted magnetic semiconductor, (La(1-x)Ca(x))(Zn(1-y) Mn(y))AsO, with a layered crystal structure isostructural to that of the 1 1 1 1 type Fe-based high-temperature superconductor LaFeAsO and the antiferromagnetic LaMnAsO. With Ca and Mn codoping into LaZnAsO, the ferromagnetic ordering occurs below the Curie temperature T(c) ~30 K. Taking advantage of the decoupled charge and spin doping, we investigate the influence of carrier concentration on the ferromagnetic ordering state. For a fixed Mn concentration of 10%, T(c) increases from 24 K to 30 K when the Ca concentration increases from 5% to 10%. Further increase of Ca concentration reduces both the coercive field and saturation moment. Muon spin relaxation measurements confirm the ferromagnetically ordered state, and clearly demonstrate that La(1-x)Ca(x))(Zn(1-y) Mn(y))AsO shares a common mechanism for the ferromagnetic exchange interaction with (Ga,Mn)As. Neutron scattering measurements show no structural transition in (La(0.90)Ca(0.10))(Zn(0.90)Mn(0.10)) AsO below 300 K. PMID- 26679222 TI - Prediction of neddylation sites from protein sequences and sequence-derived properties. AB - BACKGROUND: Neddylation is a reversible post-translational modification that plays a vital role in maintaining cellular machinery. It is shown to affect localization, binding partners and structure of target proteins. Disruption of protein neddylation was observed in various diseases such as Alzheimer's and cancer. Therefore, understanding the neddylation mechanism and determining neddylation targets possibly bears a huge importance in further understanding the cellular processes. This study is the first attempt to predict neddylated sites from protein sequences by using several sequence and sequence-based structural features. RESULTS: We have developed a neddylation site prediction method using a support vector machine based on various sequence properties, position-specific scoring matrices, and disorder. Using 21 amino acid long lysine-centred windows, our model was able to predict neddylation sites successfully, with an average 5 fold stratified cross validation performance of 0.91, 0.91, 0.75, 0.44, 0.95 for accuracy, specificity, sensitivity, Matthew's correlation coefficient and area under curve, respectively. Independent test set results validated the robustness of reported new method. Additionally, we observed that neddylation sites are commonly flexible and there is a significant positively charged amino acid presence in neddylation sites. CONCLUSIONS: In this study, a neddylation site prediction method was developed for the first time in literature. Common characteristics of neddylation sites and their discriminative properties were explored for further in silico studies on neddylation. Lastly, up-to-date neddylation dataset was provided for researchers working on post-translational modifications in the accompanying supplementary material of this article. PMID- 26679224 TI - A patient with fever, abdominal pain and bicytopenia: Trouble once again with these IgM antibodies! AB - We here report the case of a 30-year old man with a history of ulcerative colitis, who presented clinical and biological features compatible with a viral hepatitis. Initial serological results revealed the presence of IgM antibodies against many viruses, and the most likely diagnosis was viral hepatitis A. However, further investigations were performed and concluded to cytomegalovirus primary infection. PMID- 26679225 TI - The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test. AB - In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7 nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. PMID- 26679226 TI - The levels of the GluN2A NMDA receptor subunit are modified in both the neonatal and adult rat brain by an early experience involving denial of maternal contact. AB - The composition of the N-methyl-d-aspartate receptor receptor in GluN2A/GluN2B subunits is important in determining its characteristics and its role in plasticity, a property of the brain which is known to be critically affected by early experiences. In the present work we employed an early experience model involving either receipt (RER) or denial (DER) of the expected reward of maternal contact within the context of learning by the pups of a T-maze on postnatal days (PND) 10-13. We investigated the effects of the RER and DER early experiences on GluN1, GluN2A and GluN2B levels in the prefrontal cortex (PFC), hippocampus and amygdala of the rat. We show that on PND13 the DER animals had lower GluN2A levels in the PFC. In adulthood DER males had higher GluN2A levels in the hippocampus, both under basal conditions and after exposure to a novel environment. The early experiences did not affect the response to the novelty. After exposure to a novel environment animals of all three groups (DER, RER, Control) responded with an increase in GluN2A levels in the brain areas examined. We did not detect any effects on GluN1 or GluN2B levels. The alterations in GluN2A levels observed in the DER animals could in part be responsible for their behavioral phenotype, described previously, which includes an increased susceptibility for the expression of depressive-like behavior. PMID- 26679227 TI - Immunoelectron microscopic observation of the subcellular localization of kisspeptin, neurokinin B and dynorphin A in KNDy neurons in the arcuate nucleus of the female rat. AB - KNDy neurons are named for their co-expression of three neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (DynA). These cells, located in the hypothalamic arcuate nucleus (ARC), are associated with generation of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) pulses to control follicular growth and steroidogenesis. However, subcellular sorting mechanisms for secretory vesicles containing these neuropeptides have not been elucidated. In this study, we analyzed the localization pattern of kisspeptin, NKB and DynA in the ARC of the ovariectomized rat immediately treated with estrogen using immunoelectron microscopy. First, we identified neuropeptides by dual-labeled fluorescence immunohistochemistry, with results indicating all three neuropeptides co-express within individual ARC cells in female rats. Next, we investigated the subcellular localization pattern of kisspeptin, NKB, and/or DynA using post-embedding double immunoelectron microscopy, indicating that each type of neuropeptide is contained within separate and individual neurosecretory vesicles. This suggests sorting and packaging of kisspeptin, NKB and DynA is differentially regulated within KNDy neurons. Our findings facilitate understanding of regulatory mechanisms underlying kisspeptin secretion in KNDy neurons, and generation of GnRH/LH pulses induced by kisspeptin in the ARC. PMID- 26679228 TI - Selective repression of gene expression in neuropathic pain by the neuron restrictive silencing factor/repressor element-1 silencing transcription (NRSF/REST). AB - Neuropathic pain often develops following nerve injury as a result of maladaptive changes that occur in the injured nerve and along the nociceptive pathways of the peripheral and central nervous systems. Multiple cellular and molecular mechanisms likely account for these changes; however, the exact nature of these mechanisms remain largely unknown. A growing number of studies suggest that alteration in gene expression is an important step in the progression from acute to chronic pain states and epigenetic regulation has been proposed to drive this change in gene expression. In this review, we discuss recent evidence that the DNA-binding protein neuron-restrictive silencing factor/repressor element-1 silencing transcription factor (NRSF/REST) is an important component in the development and maintenance of neuropathic pain through its role as a transcriptional regulator for a select subset of genes that it normally represses during development. PMID- 26679230 TI - Endoscopic vs. conventional septoplasty: A review of the literature. AB - The aim of this review of literature was to compare conventional and endoscopic septoplasty in terms of operating time, functional efficacy and perioperative morbidity. A systematic review of the scientific literature was performed on the PubMed database, Google and Google Scholar, searching for randomized prospective trials comparing endoscopic and conventional septoplasty. The primary endpoint was operating time, and the secondary endpoints were intra- and postoperative complications, postoperative pain, hospital stay and functional result. Twenty nine articles published between 1991 and 2012 compared conventional and endoscopic septoplasty, five of which were prospective randomized trials. Operating time was shorter with endoscopic surgery (P<0.001), with less mucosal damage (P<0.01); there was less synechia (P<0.01) and residual deformity (P<0.05); and postoperative pain was milder. Endoscopic septoplasty thus shortened surgery time and reduced perioperative complications, but the functional result was the same as with conventional septoplasty. PMID- 26679229 TI - Inhibiting receptor for advanced glycation end product (AGE) and oxidative stress involved in the protective effect mediated by glucagon-like peptide-1 receptor on AGE induced neuronal apoptosis. AB - Our previous study has demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist could protect neurons from advanced glycation end products (AGEs) toxicity in vitro. However, further studies are still needed to clarify the molecular mechanism of this GLP-1 receptor -dependent action. The present study mainly focused on the effect of GLP-1 receptor agonists against the receptor for advanced glycation end products (RAGE) signal pathway and the mechanism underlying this effect of GLP-1. Firstly the data based on the SH-GLP-1R(+) and SH-SY5Y cells confirmed our previous finding that GLP-1 receptor could mediate the protective effect against AGEs. The assays of the protein activity and of the mRNA level revealed that apoptosis-related proteins such as caspase-3, caspase-9, Bax and Bcl-2 were involved. Additionally, we found that both GLP-1 and exendin-4 could reduce AGEs-induced reactive oxygen species (ROS) accumulation by suppressing the activity of nicotinamide adenine dinucleotide phosphate-oxidase. Interestingly, we also found that GLP-1 receptor activation could attenuate the abnormal expression of the RAGE in vitro and in vivo. Furthermore, based on the analysis of the protein expression and translocation level of transcription factor nuclear factor-kappaB (NF-kappaB), and the use of GLP-1 receptor antagonist exendin(9-39) and NF-kappaB inhibitor pyrrolidine dithiocarbamate, we found that the effect mediated by GLP-1 receptor could alleviate the over expression of RAGE induced by ligand via the suppression of NF-kappaB. In summary, the results indicated that inhibiting RAGE/oxidative stress was involved in the protective effect of GLP-1 on neuron cells against AGEs induced apoptosis. PMID- 26679231 TI - Benefit of contralateral hearing aid in adult cochlear implant bearers. AB - OBJECTIVES: The present study assessed the interest of a contralateral hearing aid (HA) in adult cochlear implant (CI) bearers. MATERIAL AND METHODS: The study recruited 10 French-speaking adult HA bearers with postlingual bilateral hearing loss, fitted for at least 2 years with a unilateral CI after loss of benefit from HA in one ear but continuing to use their contralateral HA: 4 male, 6 female; mean age, 58 years. All had regularly used bilateral HAs prior to CI. Audiometric assessment comprised: (1) individual ear hearing assessment on pure-tone audiometry and speech discrimination; and (2) free-field testing without aid, with CI only, with HA only and with CI plus HA, on pure-tone audiometry and speech discrimination with quiet background and on speech discrimination in noise. RESULTS: Speech discrimination was significantly improved in the bimodal condition (CI plus HA) as compared to CI alone, on all tests. In quiet, discrimination for disyllabic words was>50% in 7 cases with HA alone, in 2 cases with CI alone and in 1 case in with HA+CI. Under 0dB signal-to-noise ratio, discrimination was>50% in 1 case with HA alone, in 3 cases with CI alone and in 6 cases with HA+CI. CONCLUSION: The present results showed benefit in auditory perception in quiet and in noise with bimodal stimulation. When there is residual hearing in the non-implanted ear, a HA should be fitted; and in progressive bilateral hearing loss, CI should be suggested when HA benefit decreases in one ear. PMID- 26679232 TI - Thyroid hydatid cyst: An unusual site. PMID- 26679233 TI - Surgical treatment of vestibular schwannoma. Review of 420 cases. AB - INTRODUCTION AND OBJECTIVES: Vestibular schwannoma is the most frequent cerebellopontine angle tumor. The aim of our study is to reflect our experience in the surgical treatment of this tumor MATERIAL AND METHODS: Retrospective study of 420 vestibular schwannomas operated in our hospital between 1994-2014. We include tumor size, preoperative hearing, surgical approaches, definitive facial and hearing functional results, and complications due to surgery. RESULTS: A total of 417 patients with 420 tumors were analyzed, 209 female (50.1%) and 208 male (49.9%). Mean age at diagnosis was 49.8+/-13.2 years. The majority of the tumors were resected through a translabyrinthine approach (80.2%). Total tumor removal was achieved in 411 tumors (98.3%), and anatomic preservation of facial nerve in 404 (96.2%). Definitive facial nerve outcome was House-Brackmann grade I and II in 69.9%, and was significantly better in tumors under 20mm. Surgical complications included cerebrospinal fluid leakage in 3 patients (0.7%) and retroauricular subcutaneous collection in 16 (3.8%), 5 cases of meningitis (1.2%), 4 patients with intracraneal bleeding (0.9%), and death in 3 patients (0.7%). CONCLUSIONS: Surgery is the treatment of choice for vestibular schwannoma in the majority of patients. In our experience, the complication rate is very low and tumor size is the main factor influencing postoperative facial nerve function. PMID- 26679234 TI - Systematic Review of Behavioral Interventions Targeting Social Communication Difficulties After Traumatic Brain Injury. AB - OBJECTIVE: To determine whether behavioral interventions are beneficial for adults with social communication difficulties after traumatic brain injury (TBI). DATA SOURCES: Electronic databases were searched through October 2013 to find behavioral intervention trials. Keywords used in our search were intervention, therapy, treatment, and program combined with pragmatic disorder, pragmatic impairment, social communication disorder/impairment, conversation disorder/impairment, social disorder/impairment, cognitive-linguistic and cognitive-communication deficit; adult; and traumatic brain injury, head injury, and brain injury. Hand searches of the reference lists of relevant articles were also conducted. STUDY SELECTION: To be selected for detailed review, articles found in the initial search were assessed by 2 reviewers and had to meet the following criteria: (1) population (adults with TBI); (2) intervention (behavioral intervention); and (3) outcomes (changes in social communication). Articles needed to describe interventions that were delivered directly to adults with TBI with or without other people (such as significant others) involved. Of the 2181 articles initially identified, 15 were selected for detailed review. DATA EXTRACTION: Data were independently extracted by members of the research team, then collated and reviewed by the team. DATA SYNTHESIS: Of the 15 publications that met the study criteria, 7 were single-case design studies, 3 were randomized controlled trials, 1 was a nonrandomized controlled trial, and 4 were cohort studies. The methodological qualities of eligible articles were examined using the Physiotherapy Evidence Database and Single-Case Experimental Design rating scales. The interventions described in the studies fell into 2 broad categories: those addressing a specific impairment in social communication, and context-specific interventions with a holistic focus on social communication skills. Studies using context-sensitive approaches had been published more recently and were generally group studies with higher methodological quality. CONCLUSIONS: Overall, interventions addressing social communication skills for people with TBI were found to be beneficial irrespective of treatment approach used. While the evidence base is small and with varying levels of scientific rigor, there is a body of quality evidence that supports the use of context sensitive approaches. Further research is still required to determine the role of impairment-specific versus context-specific interventions when treating individuals with social communication difficulties after TBI to inform clinical decision-making. PMID- 26679235 TI - What Do We Know, How Do We Know It, and How Can We Best Apply It? PMID- 26679236 TI - Is Positive Fluid Balance a Problem? PMID- 26679237 TI - Nutrition Needs Should Be Modified to Consider Nutrition Status and Acuity of Illness: Lessons From the INTACT Trial. PMID- 26679238 TI - Response to Drs Jeejeebhoy and Bistrian. PMID- 26679240 TI - Authors' Response to Vermeulen et al. PMID- 26679239 TI - Consequences of the REDOXS and METAPLUS Trials: The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients? PMID- 26679241 TI - Mixed-stock analysis in green turtles Chelonia mydas: mtDNA decipher current connections among west Atlantic populations. AB - The green turtle Chelonia mydas undertakes wide-ranging migrations between feeding and nesting sites, resulting in mixing and isolation of genetic stocks. We used mtDNA control region to characterize the genetic composition, population structure, and natal origins of C. mydas in the West Atlantic Ocean, at one feeding ground (State of Rio de Janeiro, Brazil), and three Caribbean nesting grounds (French Guiana, Guadeloupe, and Suriname). The feeding ground presented considerable frequency of common haplotypes from the South Atlantic, whereas the nesting sites presented a major contribution of the most common haplotype from the Caribbean. MSA revealed multiple origins of individuals at the feeding ground, notably from Ascension Island, Guinea Bissau, and French Guiana. This study enables a better understanding of the dispersion patterns and highlights the importance of connecting both nesting and feeding areas. Effective conservation initiatives need to encompass these ecologically and geographically distinct sites as well as those corridors connecting them. PMID- 26679242 TI - Human Respiratory Syncytial Virus: Role of Innate Immunity in Clearance and Disease Progression. AB - Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed. PMID- 26679243 TI - A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin. AB - OBJECTIVES: Delafloxacin is an investigational anionic fluoroquinolone being developed to treat infections caused by Gram-positive and -negative organisms. This clinical trial evaluated the efficacy and safety of delafloxacin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs). METHODS: In a double-blind, Phase 2 trial, 256 patients were randomized (1 : 1 : 1) to 300 mg of delafloxacin, 600 mg of linezolid or 15 mg/kg vancomycin (actual body weight), each administered intravenously twice daily for 5-14 days. Randomization was stratified by infection category. The primary endpoint was the investigator's assessment of cure, defined as complete resolution of baseline signs and symptoms at follow-up. Secondary endpoints included reductions in the total areas of erythema and induration and assessments of bacterial eradication. This trial has been registered at ClinicalTrials.gov under registration number NCT01283581. RESULTS: Cure rates were significantly greater with delafloxacin versus vancomycin (mean difference: -16.3%; 95% CI, -30.3% to -2.3%; P = 0.031); differences were significant for obese patients (BMI >=30 kg/m(2); mean difference: -30.0%; 95% CI, -50.7% to -9.3%; P = 0.009), but not for non-obese patients. Cure rates with delafloxacin and linezolid were similar. Using digital measurement, the percentage decrease in total erythema area was significantly greater with delafloxacin versus vancomycin at follow-up (-96.4% versus -84.5%; P = 0.028). There were no differences in bacterial eradication among the treatment groups. The most frequently reported treatment-emergent adverse events were nausea, diarrhoea and vomiting. CONCLUSIONS: These data show that delafloxacin is effective in the treatment of ABSSSIs and is well tolerated. PMID- 26679244 TI - Clinical Salmonella Typhimurium ST34 with metal tolerance genes and an IncHI2 plasmid carrying oqxAB-aac(6')-Ib-cr from Europe. PMID- 26679245 TI - Macrolide resistance gene erm(TR) and erm(TR)-carrying genetic elements in Streptococcus agalactiae: characterization of ICESagTR7, a new composite element containing IMESp2907. AB - OBJECTIVES: The objective of this study was to investigate macrolide-resistant Streptococcus agalactiae isolates harbouring erm(TR), an erm(A) gene subclass, with emphasis on their erm(TR)-carrying genetic elements. Four erm(TR)-carrying elements have been described to date: three closely related (ICE10750-RD.2, Tn1806 and ICESp1108) in Streptococcus pyogenes, Streptococcus pneumoniae and S. pyogenes, respectively; and one completely different (IMESp2907, embedded in ICESp2906 to form ICESp2905) in S. pyogenes. METHODS: Seventeen macrolide resistant erm(TR)-positive S. agalactiae isolates were phenotypically and genotypically characterized. Their erm(TR)-carrying elements were explored by analysing the distinctive recombination genes of known erm(TR)-carrying integrative and conjugative elements (ICEs) and by PCR mapping. The new genetic context and organization of IMESp2907 in S. agalactiae were explored using several experimental procedures and in silico analyses. RESULTS: Five isolates harboured ICE10750-RD.2/Tn1806, five isolates harboured ICESp1108 and five isolates bore unknown erm(TR)-carrying elements. The remaining two isolates, exhibiting identical serotypes and pulsotypes, harboured IMESp2907 in a new genetic environment, which was further investigated in one of the two isolates, SagTR7. IMESp2907 was circularizable in S. agalactiae, as described in S. pyogenes. The new IMESp2907 junctions were identified based on its site-specific integration; the att sites were almost identical to those in S. pyogenes. In strain SagTR7, erm(TR)-carrying IMESp2907 was embedded in an erm(TR)-less internal element related to ICE10750-RD.2/Tn1806, which, in turn, was embedded in an ICESde3396-like element. The resulting whole ICE, ICESagTR7 (~129 kb), was integrated into the chromosome downstream of the rplL gene, and was excisable in circular form and transferable by conjugation. CONCLUSIONS: This is the first study exploring erm(TR)-carrying genetic elements in S. agalactiae. PMID- 26679246 TI - Dolutegravir and elvitegravir plasma concentrations following cessation of drug intake. AB - OBJECTIVES: To evaluate dolutegravir and elvitegravir/cobicistat pharmacokinetics in HIV-negative volunteers up to 10 days after drug cessation. METHODS: Healthy volunteers received 50 mg of dolutegravir once-daily for 10 days, then underwent a 9 day wash-out period, and then received elvitegravir/cobicistat as part of Stribild((r)) (245 mg of tenofovir, 200 mg of emtricitabine, 150 mg of elvitegravir and 150 mg of cobicistat) for 10 days. Serial pharmacokinetic (PK) sampling occurred prior to the final dose of each course and at regular intervals for up to 216 h (10 days) after drug cessation. Concentrations were determined by LC-MS/MS, and PK parameters were illustrated as geometric mean and 90% CI. RESULTS: Seventeen volunteers completed the study. For dolutegravir, plasma terminal elimination t1/2 to the last measurable concentration (within 216 h) was longer than its t1/2 within the dosing interval (0-24 h): 14.3 h (12.9-15.7 h) versus 23.1 h (19.7-26.6 h); conversely, the terminal elimination t1/2 for elvitegravir was lower than its t1/2 within the dosing interval (0-24 h): 10.8 h (9.7-13.0 h) versus 5.2 h (4.7-6.1 h). Dolutegravir concentrations were above the protein-adjusted (PA) IC90 (64 ng/mL) in 100% of subjects after 36 and 48 h and in 94% after 60 and 72 h. All subjects had detectable dolutegravir concentrations at 96 h, a mean of 23.5% above the IC90. Elvitegravir concentrations were above the PA IC95 (45 ng/mL) in 100% of subjects at 24 h, 65% at 36 h but 0% after 48 h. CONCLUSIONS: Our data show marked differences in the elimination rates of dolutegravir and elvitegravir following treatment interruption, which is likely to impact the extent to which drug doses can be delayed or missed. They suggest that clinical differences may emerge in patients who have suboptimal adherence. PMID- 26679247 TI - Concentrations of tenofovir, lamivudine and efavirenz in mothers and children enrolled under the Option B-Plus approach in Malawi. AB - OBJECTIVES: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to child transmission in Malawi and to assess the maternal virological response after 1 year of treatment. PATIENTS AND METHODS: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology. RESULTS: In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08), while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load. CONCLUSIONS: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery. PMID- 26679248 TI - Differential impact of ramRA mutations on both ramA transcription and decreased antimicrobial susceptibility in Salmonella Typhimurium. AB - OBJECTIVES: This study was focused on analysing the heterogeneity of mutations occurring in the regulators of efflux-mediated MDR in Salmonella Typhimurium. Moreover, the impact of such mutations on impairing the transcription of ramA, acrB, tolC and acrF was also assessed as was the impact on the resistance or decreased susceptibility phenotype. METHODS: Strains were selected in vitro under increasing ciprofloxacin concentrations. Etest and broth microdilution tests were used to determine the MICs of several unrelated compounds. Screening of mutations in the quinolone target genes and MDR regulators was performed. RT-PCR analysis was used to detect the levels of expression of acrB, tolC, ompF, acrF, emrB, acrR, ramA, soxS and marA. RESULTS: All mutant strains showed increased MICs of most of the antimicrobials tested, with the exception of kanamycin. Mutations in the quinolone target genes did not occur in all the mutants, which all harboured mutations in the ramRA regulatory region. All the mutants overexpressed ramA, tolC and acrB (only tested in 60-wt derivatives), whereas differential results were seen for the remaining genes. CONCLUSIONS: Mutations in the ramRA region related to resistance and/or decreased susceptibility to antimicrobials predominate in Salmonella. There is heterogeneity in the types of mutations, with deletions affecting RamR-binding sites having a greater impact on ramA expression and the MDR phenotype. PMID- 26679252 TI - Successful treatment with ceftriaxone induction and minocycline maintenance for gastrointestinal Whipple's disease. PMID- 26679251 TI - Genetic characterization of a novel blaDIM-2-carrying megaplasmid p12969-DIM from clinical Pseudomonas putida. AB - OBJECTIVES: To characterize a blaDIM-2-carrying 409 kb megaplasmid p12969-DIM of Pseudomonas putida 12969 from a patient with pneumonia in China. METHODS: The complete nucleotide sequence of p12969-DIM was determined with a paired-end library and a mate-pair library using next-generation sequencing technology. RESULTS: blaDIM-2, a close blaDIM-1 variant, was identified in p12969-DIM. DIM-2 differs from DIM-1 by two amino acid substitutions Ser119Leu and Ser209Pro. The p12969-DIM backbone is highly similar to pOZ176, but the IncP-2-type stability/replication/conjugal transfer system in the pOZ176 backbone is absent from p12969-DIM. The p12969-DIM accessory regions, a 45.7 kb MDR and a novel insertion sequence, ISPpu23, are almost entirely distinct from pOZ176. The MDR region contains a novel Tn21-subgroup transposon Tn6286 inserted with two class 1 integrons, In1225 and In1226; a Tn5503-family transposon-like element inserted with a strAB locus; and a novel Tn21-subgroup transposon-like element inserted with a class 1 integron, In1224. The three integrons carry blaDIM-2 as well as a number of additional genes conferring resistance to quinolones, aminoglycosides, chloramphenicol, florfenicol, trimethoprim, streptomycin, quaternary ammonium compounds and sulphonamides. p12969-DIM has two distinct replication/stability systems, repA/parAB-parB2 of an unknown incompatibility group in the backbone and repABC/mazFE of the IncQ2 group in the MDR region. CONCLUSIONS: The MDR region of p12969-DIM harbours many resistance genes as well as a second replication/stability system. This article is the first report of a fully sequenced blaDIM-carrying plasmid. PMID- 26679249 TI - HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels. AB - OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA <=3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI. PMID- 26679254 TI - New insights into the survival mechanisms of rifampicin-resistant Mycobacterium tuberculosis. AB - OBJECTIVES: Rifampicin is considered the most important antibiotic for treating TB, but unfortunately Mycobacterium tuberculosis is rapidly developing resistance to this drug. Despite the fervent research efforts to date, TB is still a major global problem, and hence new approaches are necessary to better characterize this disease, especially the mechanisms relating to drug resistance. METHODS: Using a two-dimensional GC-coupled time-of-flight MS metabolomics approach, the most important metabolite markers characterizing rifampicin-resistant M. tuberculosis were identified. RESULTS: The metabolite markers identified indicate instability in rifampicin-resistant M. tuberculosis mRNA, induced by the rpoB mutation. This results in a total depletion of aconitic acid, due to a shift in aconitase functionality towards mRNA binding and stability, and away from energy production and growth, and a subsequent increased dependency on alternative energy sources, fatty acids in particular. A number of other metabolic changes were observed, confirming an additional survival response for maintaining/remodelling the cell wall. CONCLUSIONS: This study shows the value of a metabolomics approach to biological investigations in a quest to better understand disease-causing organisms and their tolerance to existing medications, which would in the future undoubtedly assist in the development of alternative treatment approaches. PMID- 26679253 TI - Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections. AB - OBJECTIVES: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. METHODS: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. RESULTS: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. CONCLUSIONS: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. PMID- 26679256 TI - Phosphate binders, past - present - future. A critical appraisal. PMID- 26679255 TI - Quaternary ammonium surfactant structure determines selective toxicity towards bacteria: mechanisms of action and clinical implications in antibacterial prophylaxis. AB - OBJECTIVES: Broad-spectrum antimicrobial activity of quaternary ammonium surfactants (QAS) makes them attractive and cheap topical prophylactic options for sexually transmitted infections and perinatal vertically transmitted urogenital infections. Although attributed to their high affinity for biological membranes, the mechanisms behind QAS microbicidal activity are not fully understood. We evaluated how QAS structure affects antimicrobial activity and whether this can be exploited for use in prophylaxis of bacterial infections. METHODS: Acute toxicity of QAS to in vitro models of human epithelial cells and bacteria were compared to identify selective and potent bactericidal agents. Bacterial cell viability, membrane integrity, cell cycle and metabolism were evaluated to establish the mechanisms involved in selective toxicity of QAS. RESULTS: QAS toxicity normalized relative to surfactant critical micelle concentration showed n-dodecylpyridinium bromide (C12PB) to be the most effective, with a therapeutic index of ~10 for an MDR strain of Escherichia coli and >20 for Neisseria gonorrhoeae after 1 h of exposure. Three modes of QAS antibacterial action were identified: impairment of bacterial energetics and cell division at low concentrations; membrane permeabilization and electron transport inhibition at intermediate doses; and disruption of bacterial membranes and cell lysis at concentrations close to the critical micelle concentration. In contrast, toxicity to mammalian cells occurs at higher concentrations and, as we previously reported, results primarily from mitochondrial dysfunction and apoptotic cell death. CONCLUSIONS: Our data show that short chain (C12) n-alkyl pyridinium bromides have a sufficiently large therapeutic window to be good microbicide candidates. PMID- 26679257 TI - Ingestion of frying fat leads to activation of the endoplasmic reticulum stress induced unfolded protein response in the duodenal mucosa of pigs. AB - SCOPE: Ingestion of oxidized fats (OF) causes activation of stress signaling pathways such as nuclear factor-erythroid 2-related factor 2 (Nrf2) in the intestine. Activation of this pathway is mediated by ER stress-induced unfolded protein response (UPR). Herein, we hypothesized that ingestion of OF causes ER stress-induced UPR in duodenal mucosa of pigs. METHODS AND RESULTS: Six-wk-old cross-bred pigs received either a control diet with fresh fat or a diet with OF for 29 days. Pigs fed OF exhibited increased phosphorylation of the ER stress downstream target eukaryotic translation initiation factor 2alpha and induction of several genes involved in ER stress-induced UPR and Nrf2 target genes in duodenal mucosa. No signs of an impaired intestinal barrier function or a systemic inflammatory response could be found in pigs fed OF. CONCLUSION: Activation of ER stress-induced UPR by OF in the duodenal mucosa in pigs might be interpreted as a cytoprotective response to stress factors associated with ingestion of OF. Given the similarities between pigs and humans with respect to digestive physiology, it is possible that regular ingestion of fried foods containing OF activates the ER stress-induced UPR also in the intestinal mucosa of humans. PMID- 26679258 TI - Neuroinflammation after Subarachnoid Hemorrhage: a Consolidated Theory? PMID- 26679259 TI - Flow Diverters for Treatment of Intracranial Aneurysms: Technical and Clinical Updates. PMID- 26679250 TI - Tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients treated for tuberculosis: the ANRS 129 BKVIR trial. AB - BACKGROUND: HIV-infected patients with TB need simplified, effective and well tolerated antiretroviral regimens. METHODS: The French ANRS 129 BKVIR open trial evaluated the once-daily tenofovir DF/emtricitabine and efavirenz combination, started within 12 weeks after TB treatment initiation, in antiretroviral-naive HIV-1-infected patients. Success was defined as an HIV-1 RNA <50 copies/mL and TB cure at 48 weeks. RESULTS: TB was confirmed microbiologically (90%) or histologically (10%) in 69 patients (71% male; median age 43 years; 54% born in Africa). The median time between TB treatment initiation and antiretroviral therapy was 8 weeks (range 1-22 weeks). At baseline, median HIV-1 RNA was 5.4 log10 copies/mL and median CD4 cell count 74 cells/mm(3). In the ITT analysis, combined success at week 48 was achieved in 57/69 patients (83%, 95% CI 74-92). Twelve patients did not achieve virological success, and TB was not cured in one of them. Among the 47 patients who fully adhered to the strategy, the success rate was 96% (95% CI 90-100) and was not affected by low rifampicin and isoniazid serum concentrations. Forty-nine serious adverse events were reported in 31 patients (45%), and 11 led to antiretroviral drug interruption. All adverse events resolved. The immune reconstitution inflammatory syndrome occurred in 23 patients (33%, 95% CI 22-44), and was associated with a low baseline BMI (P = 0.03) and a low haemoglobin level (P = 0.02). CONCLUSION: These results support the use of tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients with TB. PMID- 26679260 TI - Primary Intracranial Epidermoid Carcinoma with Diffuse Leptomeningeal Carcinomatosis: Report of Two Cases. AB - BACKGROUND: Malignant degeneration of epidermoid cyst (EC) with accompanying leptomeningeal carcinomatosis (LC) at presentation is extremely rare. We add two cases to the literature, including the first case of primary brainstem involvement with simultaneous diffuse LC, and discuss clinical and radiological cues to differentiate benign and malignant epidermoid tumors for early diagnosis. CASE DESCRIPTION: The first patient in this report was a 54-year-old woman with recurrent aseptic meningitis and hydrocephalus. Imaging revealed a prepontine and parapontine extra-axial EC with an intra-axial brainstem ring-enhancing cystic lesion, diffuse leptomeningeal enhancement, and intradural extramedullary nodular deposits throughout the spine. Surgical decompression of the cysts confirmed the diagnosis of invasive primary squamous cell carcinoma of the brainstem and benign epidermoid tumor of the cerebellopontine cistern. The second patient was a 37 year-old woman with extensive left-sided cranial neuropathies. Imaging revealed prepontine and parapontine enhancing and nonenhancing deposits along multiple cranial nerves and diffuse leptomeningeal nodular enhancement in the thoracolumbar spine. A biopsy confirmed the diagnosis of infiltrative, poorly differentiated carcinoma adjacent to a benign EC. Both patients underwent systemic screening to rule out metastatic disease. CONCLUSIONS: These cases illustrate that a high index of clinical suspicion is necessary for early diagnosis of disseminated disease in cases of recurrent episodes of aseptic meningitis. In cases of primary benign EC, aggressive resection should be attempted to reduce the risk of malignant degeneration. A separate biopsy specimen from the enhancing portion of the tumor is used to rule out an underlying coexisting malignancy. Multimodal management carries the best prognosis for primary intracranial squamous cell carcinoma with LC. PMID- 26679261 TI - Epistemology of Brain Arteriovenous Malformations. PMID- 26679262 TI - SEEG, Happy Anniversary! PMID- 26679263 TI - Pipeline Embolization Device: Long-Term Outcome Data Flows In. PMID- 26679265 TI - Spatial clustering of "measured" and "unmeasured" risk factors for HIV infections in hyper-endemic communities in KwaZulu-Natal, South Africa: results from geoadditive models. AB - Sub-Saharan Africa contains more than 60% of all HIV infections worldwide. HIV prevalence was currently estimated to be at least 15% in KwaZulu-Natal and the epidemic is described as hyper-endemic. Knowledge of spatial clustering of risk factors which are linked to new HIV infections is important for prioritizing areas to change the trajectory of the epidemic. Geoadditive models were used to investigate spatial characteristics of the risk factors from two clinical trial units (Umkomaas and Botha's Hill) in the province of KwaZulu-Natal, South Africa. Study population was a cohort of women who screened and enrolled in an HIV prevention biomedical intervention trial. The results suggest high HIV incidence rates (5.8 and 8 per 100 person-year). Considerable spatial variations in behavioural factors within a relatively small geographical region, low level of education, early age at sexual debut, higher number of sexual partners, not being married/cohabitating with a sexual partner and sexual activity in exchange for money, gift and drugs were all determined to be clustered in certain regions; they were accounted for 25% (Umkomaas) and 65% (Botha's Hill) of the excess new HIV infections in two clinical trial units. Results from our study highlighted existence of significant spatial heterogeneity in "measured" and "unmeasured" risk factors in a relatively small region. As the HIV funding has been declining, identifying, targeting and reaching the most-at-risk individuals will likely play a significant role in developing the most efficient and cost-effective prevention programmes and subsequently will change the trajectory of the epidemic. PMID- 26679264 TI - Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior. AB - INTRODUCTION: Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. MATERIALS AND METHODS: The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). RESULTS: The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. DISCUSSION: The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed. PMID- 26679266 TI - Perceived social support among HIV patients newly enrolled in care in rural Ethiopia. AB - Social support significantly enhances physical and mental health for persons with human immunodeficiency virus (HIV). We surveyed 142 rural Ethiopian HIV patients newly enrolled in care for perceived social support and factors associated with low support levels. Using the Social Provisions Scale (SPS), the mean summary score was 19.1 (possible scores = 0-48). On six SPS subscales, mean scores (possible scores = 0-8), were: Reliable Alliance (others can be counted on for tangible assistance) = 2.8, Attachment (emotional closeness providing sense of security) = 2.9, Reassurance of Worth (recognition of competence and value by others) = 3.2, Guidance (provision of advice or information by others) = 3.2, Social Integration (belonging to a group with similar interests and concerns) = 3.5, and Nurturance (belief that others rely on one for their well-being) = 3.6. In multivariate analysis, factors significantly associated with lower social support scores were: lower education level (did not complete primary school) (p = .019), lower total score on knowledge items about HIV care/treatment (p = .038), and greater number of external stigma experiences in past three months (p < .001); greater number of chronic disease symptoms was of borderline significance (p = .098). Among rural Ethiopian patients newly entering HIV care, we found moderate and varying levels of perceived social support, with lowest scores for subscales reflecting emotional closeness and reliance on others for tangible assistance. Given that patients who have recently learned their diagnosis and entered care may be an especially vulnerable group, programs to help identify and address social support needs can provide multiple benefits in facilitating the best possible physical, emotional and functional quality of life for people living with HIV. PMID- 26679267 TI - Evaluating patterns in retention, continuation, gaps, and re-engagement in HIV care in a Medicaid-insured population, 2006-2012, United States. AB - We used the US-based MarketScan((r)) Medicaid Multi-state Databases to determine the un-weighted proportion of publically insured persons with HIV that were retained, continued, and re-engaged in care. Persons were followed for up to 84 months. Cox proportional hazards models were conducted to determine factors associated with gaps in care. Of the 6463 HIV cases identified in 2006, 61% were retained during the first 24 months, and 53% continued in care through 78 months. Between 8% and 30% experienced a gap in care, and 59% of persons who experienced a gap in care later re-engaged in care. Persons with one or more Charlson co morbidities (HR 0.72, 95% CI 0.64-0.81), ages 40-59 (0.79, 0.71-0.88), mental illness diagnosis (0.79, 0.72-0.87), hepatitis C co-infection (0.83, 0.75-0.93), and female sex (0.86, 0.78-0.94) were less likely to experience a gap in care. Between 27% and 38% of those not retained in care continued to receive HIV related laboratory services. This Medicaid claims database combines features of both clinic visits-based and surveillance lab-based surrogate measures to give a more complete picture of engagement in care than single-facility-based studies. PMID- 26679268 TI - Resilience, ageing, and quality of life in long-term diagnosed HIV-infected patients. AB - Resilience is a predictor of emotional well-being and psychological adjustment in people living with HIV infection. We report the results of a cross-sectional study in which we evaluated resilience and its association with perception of ageing, coping strategies, quality of life, and emotional status in a group of long-term diagnosed HIV-infected patients. The analysis included 151 consecutive participants (57.6% men). Resilience was moderately high to high in 65 (43%) participants, moderately low to moderate in 57 (37.7%), and very low in 29 (19.2%). Univariate and multivariate analyses were performed. Two factors of perception of ageing (good cognitive self-concept and good subjective perception of social relationships), the use of positive reframing as a coping strategy and better emotional status remained associated with high resilience. Our findings suggest that successful ageing is possible in people living with HIV infection. Resilience seems to play a key role in the ageing process. PMID- 26679269 TI - The church and paediatric HIV care in rural South Africa: a qualitative study. AB - Religion has substantial - positive and negative - influence on South Africa's HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector. PMID- 26679271 TI - Direct observation of laser guided corona discharges. AB - Laser based lightning control holds a promising way to solve the problem of the long standing disaster of lightning strikes. But it is a challenging project due to insufficient understanding of the interaction between laser plasma channel and high voltage electric filed. In this work, a direct observation of laser guided corona discharge is reported. Laser filament guided streamer and leader types of corona discharges were observed. An enhanced ionization took place in the leader (filament) through the interaction with the high voltage discharging field. The fluorescence lifetime of laser filament guided corona discharge was measured to be several microseconds, which is 3 orders of magnitude longer than the fluorescence lifetime of laser filaments. This work could be advantageous towards a better understanding of laser assisted leader development in the atmosphere. PMID- 26679270 TI - Treatment and disease outcomes of migrants from low- and middle-income countries in the Australian HIV Observational Database cohort. AB - People from culturally and linguistically diverse backgrounds, including low- and middle-income countries, account for a third of new HIV diagnoses in Australia and are a priority for HIV prevention and treatment programs. We describe the demographic and clinical characteristics of participants in the Australian HIV Observational Database (AHOD) and compare disease outcomes, progression to AIDS and treatment outcomes of those born in low- and middle-income countries, with those born in high-income countries and Australia. All participants enrolled in AHOD sites where country of birth is routinely collected were included in the study. Age, CD4 count, HIV viral load, antiretroviral therapy, hepatitis co infection, all-cause mortality and AIDS illness were analysed. Of 2403 eligible participants, 77.3% were Australian born, 13.7% born in high-income countries and 9.0% born in middle- or low-income countries. Those born in Australia or high income countries were more likely to be male (96%) than those from middle- or low income countries (76%), p < .0001 and more likely to have acquired HIV via male to male sexual contact (77%; 79%) compared with those from middle- or low-income countries (50%), p < .0001. At enrolment, mean CD4 cell count was higher in Australian born (528 cells/uL) than both those born in high-income countries (468 cells/uL) and those born in middle- and low-income countries (451 cells/uL), p < .0001; whereas the mean HIV RNA level (log10 copies/mL) was similar in all three groups (4.44, 4.76 and 4.26, respectively), p = .19.There was no difference in adjusted incidence risk ratios for all-cause mortality and AIDS incidence in all three groups, p = .39. These findings reflect successful outcomes of people born in low- and middle-income countries once engaged in HIV care. PMID- 26679282 TI - Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta-analysis of seven phase III trials. AB - This meta-analysis of seven randomized, placebo-controlled studies (total 3222 patients) evaluated whether type 2 diabetes (T2D) duration affects the changes in blood glucose control and body weight that can be achieved with liraglutide and placebo. With liraglutide 1.2 mg, shorter diabetes duration was associated with a significantly greater, but clinically non-relevant, difference in glycated haemoglobin (HbA1c) reduction (p < 0.05), i.e. a 0.18% (1.96 mmol/mol) reduction in HbA1c per 10 years shorter diabetes duration. With liraglutide 1.8 mg, shorter diabetes duration was associated with a small but statistically significant trend for greater fasting plasma glucose (FPG) reduction (p < 0.05), i.e. a 0.38 mmol/l reduction in FPG per 10 years shorter diabetes duration. Neither the liraglutide 1.8 mg nor placebo results showed a significant association between HbA1c and diabetes duration and neither the liraglutide 1.2 mg nor placebo results showed a significant association between FPG and diabetes duration. Likewise, neither liraglutide nor placebo showed a significant association between change in weight and diabetes duration. These results suggest diabetes duration has a clinically negligible effect on achievable blood glucose control and weight outcomes with liraglutide and placebo in patients with T2D. PMID- 26679283 TI - Traceability in stem cell research: from participant sample to induced pluripotent stem cell and back. AB - This paper describes a traceability system developed for the Stem cells for Biological Assays of Novel drugs and prediCtive toxiCology consortium. The system combines records and labels that to biological material across geographical locations and scientific processes from sample donation to induced pluripotent stem cell line. The labeling system uses a unique identification number to link every aliquot of sample at every stage of the reprogramming pathway back to the original donor. Only staff at the clinical recruitment site can reconnect the unique identification number to the identifying details of a specific donor. This ensures the system meets ethical and legal requirements for protecting privacy while allowing full traceability of biological material. The system can be adapted to other projects and for use with different primary sample types. PMID- 26679284 TI - Tailoring surgery to elderly patients with cancer. PMID- 26679285 TI - Correspondence. PMID- 26679286 TI - Reply. PMID- 26679287 TI - Two-Way Fluid-Gas Exchange Syringe for Postvitrectomy Patients in Outpatient Setting. PMID- 26679289 TI - A new approach for electrical properties estimation using a global integral equation and improvements using high permittivity materials. AB - Electrical Properties Tomography (EPT) using MRI is a technique that has been developed to provide a new contrast mechanism for in vivo imaging. Currently the most common method relies on the solution of the homogeneous Helmholtz equation, which has limitations in accurate estimation at tissue interfaces. A new method proposed in this work combines a Maxwell's integral equation representation of the problem, and the use of high permittivity materials (HPM) to control the RF field, in order to reconstruct the electrical properties image. The magnetic field is represented by an integral equation considering each point as a contrast source. This equation can be solved in an inverse method. In this study we use a reference simulation or scout scan of a uniform phantom to provide an initial estimate for the inverse solution, which allows the estimation of the complex permittivity within a single iteration. Incorporating two setups with and without the HPM improves the reconstructed result, especially with respect to the very low electric field in the center of the sample. Electromagnetic simulations of the brain were performed at 3T to generate the B1(+) field maps and reconstruct the electric properties images. The standard deviations of the relative permittivity and conductivity were within 14% and 18%, respectively for a volume consisting of white matter, gray matter and cerebellum. PMID- 26679288 TI - Development and testing of hyperpolarized (13)C MR calibrationless parallel imaging. AB - A calibrationless parallel imaging technique developed previously for (1)H MRI was modified and tested for hyperpolarized (13)C MRI for applications requiring large FOV and high spatial resolution. The technique was demonstrated with both retrospective and prospective under-sampled data acquired in phantom and in vivo rat studies. A 2-fold acceleration was achieved using a 2D symmetric EPI readout equipped with random blips on the phase encode dimension. Reconstructed images showed excellent qualitative agreement with fully sampled data. Further acceleration can be achieved using acquisition schemes that incorporate multi dimensional under-sampling. PMID- 26679290 TI - Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules. AB - The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the number of false alerts for CSD small molecule X ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall number of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations. PMID- 26679291 TI - Are parents really that important to managing vaccination pain during infancy? PMID- 26679293 TI - Low Protein A20 in Minor Salivary Glands is Associated with Lymphoma in Primary Sjogren's Syndrome. AB - Patients with primary Sjogren's syndrome (pSS) have an increased risk of developing lymphomas, particularly the subtype mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic antigen stimulation and increased activation of nuclear factor-kappaB (NF-kappaB) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF-kappaB. A recent study of pSS associated MALT lymphomas identified potential functional abnormalities in the TNFAIP3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry (IHC) in minor salivary glands (MSGs) and lymphoma tissue sections of patients with pSS and investigate a potential association with lymphoma development. Protein A20 staining in lymphocytes was scored in four categories (0 = negative, 1 = weak, 2 = moderate and 3 = strong). For statistical purposes, these scores were simplified into negative (scores 0-1) and positive (scores 2-3). We investigated associations between protein A20 staining, focus scores, germinal centre (GC)-like structures and monoclonal B cell infiltration in MSGs. MSG protein A20 staining was weaker in pSS patients with lymphomas than in those without lymphomas (P = 0.01). Weak protein A20 staining was also highly associated with a lack of GC formation (P < 0.01). Finally, weaker A20 staining was observed in the majority of pSS-associated MALT lymphoma tissues. In conclusion, we found absent or weak protein A20 immunoreactivity in MSGs of patients with pSS with lymphomas. This finding indicates that protein A20 downregulation in lymphocytes might be a mechanism underlying lymphoma genesis in patients with pSS. PMID- 26679292 TI - Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer. AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with an immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear. In this study, we investigated the effects of circulating MDSC subsets on the peripheral lymphocytes of patients with head and neck tumors. A significant accumulation of CD15+ granulocytic MDSC (G-MDSC) and CD14+ monocytic MDSC (M-MDSC) was demonstrated in HNSCC patients. The percentage of G-MDSC showed an inverse correlation with the percentage of T cells in the peripheral blood. The increased G-MDSC was significantly associated with advanced clinical stage and poor prognosis of HNSCC patients. The proliferation and viability of T cells were suppressed by CD15+ cells, and the suppression was reversed by adding the hydrogen peroxide scavenger catalase. However, iNKT cell activation upon alpha galactosylceramide (alphaGalCer) stimulation was not affected by the presence or absence of CD15+ G-MDSC. These results indicate that increased G-MDSC negatively affects peripheral T cell immunity, but not iNKT cells, in HNSCC patients, and that T cells are more sensitive to hydrogen peroxide produced by G-MDSC than iNKT cells. Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with alphaGalCer may remain effective in the presence of G MDSC. PMID- 26679294 TI - Identification of potential mitochondrial CLPXP protease interactors and substrates suggests its central role in energy metabolism. AB - Maintenance of mitochondria is achieved by several mechanisms, including the regulation of mitochondrial proteostasis. The matrix protease CLPXP, involved in protein quality control, has been implicated in ageing and disease. However, particularly due to the lack of knowledge of CLPXP's substrate spectrum, only little is known about the pathways and mechanisms controlled by this protease. Here we report the first comprehensive identification of potential mitochondrial CLPXP in vivo interaction partners and substrates using a combination of tandem affinity purification and differential proteomics. This analysis reveals that CLPXP in the fungal ageing model Podospora anserina is mainly associated with metabolic pathways in mitochondria, e.g. components of the pyruvate dehydrogenase complex and the tricarboxylic acid cycle as well as subunits of electron transport chain complex I. These data suggest a possible function of mitochondrial CLPXP in the control and/or maintenance of energy metabolism. Since bioenergetic alterations are a common feature of neurodegenerative diseases, cancer, and ageing, our data comprise an important resource for specific studies addressing the role of CLPXP in these adverse processes. PMID- 26679296 TI - Phylogenetic study of Ameiurus melas based on complete mitochondrial DNA sequence. AB - In our research, 16 sets of primers were used to amplify contiguous, overlapping segments of the complete mitochondrial DNA (mtDNA) of Ameiurus melas. The total length of the mitochondrial genome is 16 512 bp and deposited in the GenBank with accession no. KT804702. The gene arrangement and transcriptional direction were similar to other bony fishes which contained 37 genes (13 protein-coding genes, 2 ribosomal RNA, and 22 transfer RNAs) and a major non-coding control region. The G contents were lowest (17.36%) and the nucleotide skewness for the coding strands of A. melas (GC-skew = -0.24) is biased toward G and the negative GC-skew ranges from -0.44 (ND6) to -0.13 (CO1). The phylogenetic studies indicate that A. melas and the Ictalurus punctatus are cluster together, they are sister group. However, the phylogenetic relationship of other Cyprininae has some differences, such as Pangasianodon gigas and Silurus asotus, which need further research. PMID- 26679295 TI - The Feasibility, Acceptability, and Efficacy of Delivering Internet-Based Self Help and Guided Self-Help Interventions for Generalized Anxiety Disorder to Indian University Students: Design of a Randomized Controlled Trial. AB - BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common mental disorders among university students; however, many students go untreated due to treatment costs, stigma concerns, and limited access to trained mental health professionals. These barriers are heightened in universities in India, where there are scant mental health care services and severe stigma surrounding help seeking. OBJECTIVE: To evaluate the feasibility, acceptability, and efficacy of Internet-based, or "online," cognitive behavioral therapy (CBT)-based unguided and guided self-help interventions (using the programs GAD Online and Lantern, respectively) to reduce GAD symptoms in students with clinical and subthreshold GAD and, ultimately, reduce the prevalence and incidence of GAD among the student population. METHODS: Students will be recruited via 3 colleges in Hyderabad, India, and referred for a campus-wide online screening. Self-report data will be collected entirely online. A total of 300 qualifying students will be randomized in a 1:1:1 ratio to receive GAD Online, Lantern, or to be in a wait-list control condition, stratified by clinical and subthreshold GAD symptomatology. Students will complete a postintervention assessment after 3 months and a follow-up assessment 6 months later, at which point students in the wait-list control condition will receive one of the programs. The primary outcome is GAD symptom severity at 3 months postintervention. Secondary outcomes include GAD caseness at 9 months, other anxiety and depression symptoms, self-efficacy, and functional measures (eg, sleep, social functioning) at 3 and 9 months, respectively. Primary analyses will be differences between each of the intervention groups and the wait list control group, analyzed on an intention-to-treat (ITT) basis using mixed design ANOVA. RESULTS: The study commenced in February 2015. The sample was recruited over a 3-week period at each college. The trial is expected to end in December 2015. CONCLUSIONS: This trial will be the first to evaluate the use of Internet-based CBT programs compared with a wait-list control group for the treatment of GAD among students in Indian universities. If effective, these programs have the potential to reduce the mental health care treatment gap by providing readily accessible, private, and cost-effective evidence-based care to students with GAD who do not currently receive the treatment they need. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410265 http://clinicaltrials.gov/ct2/show/NCT02410265 (Archived by WebCite at http://www.webcitation.org/6ddqH6Rbt). PMID- 26679297 TI - Pretransplant frailty is associated with decreased survival after lung transplantation. AB - BACKGROUND: Frailty is a condition of increased vulnerability to adverse health outcomes. Although frailty is an important prognostic factor for many conditions, the effect of frailty on mortality in lung transplantation is unknown. Our objective was to assess the association of frailty with survival after lung transplantation. METHODS: We performed a retrospective cohort analysis of all adult lung transplant recipients at our institution between 2002 and 2013. Frailty was assessed using the frailty deficit index, a validated instrument that assesses cumulative deficits for up to 32 impairments and measures the proportion of deficits present (with frailty defined as >0.25). We examined the association between frailty and survival, adjusting for age, sex, and bilateral (vs single) lung transplant using Cox proportional hazard regression models. RESULTS: Among 144 lung transplant patients, 102 (71%) completed self-reported questionnaires necessary to assess the frailty deficit index within 1 year before lung transplantation. Frail patients (n = 46) had an increased risk of death, with an adjusted hazard ratio (HR) of 2.24 (95% confidence interval [CI], 1.22-4.19; p = 0.0089). Frailty was not associated with an increased duration of mechanical ventilation (median, 2 vs 2 days; p = 0.26), intensive care unit length of stay (median, 7.5 vs 6 days; p = 0.36) or hospital length of stay after transplantation (median, 14 vs 10.5 days; p = 0.26). CONCLUSIONS: Pre-transplant frailty was independently associated with decreased survival after lung transplantation. Pre-transplant frailty may represent an important area for intervention to improve candidate selection and lung transplant outcomes. PMID- 26679298 TI - Dynamical Correlation Effects on Photoisomerization: Ab Initio Multiple Spawning Dynamics with MS-CASPT2 for a Model trans-Protonated Schiff Base. AB - We investigate the photoisomerization of a model retinal protonated Schiff base (trans-PSB3) using ab initio multiple spawning (AIMS) based on multistate second order perturbation theory (MSPT2). Discrepancies between the photodynamical mechanism computed with three-root state-averaged complete active space self consistent field (SA-3-CASSCF, which does not include dynamic electron correlation effects) and MSPT2 show that dynamic correlation is critical in this photoisomerization reaction. Furthermore, we show that the photodynamics of trans PSB3 is not well-described by predictions based on minimum energy conical intersections (MECIs) or minimum energy conical intersection (CI) seam paths. Instead, most of the CIs involved in the photoisomerization are far from MECIs and minimum energy CI seam paths. Thus, both dynamical nuclear effects and dynamic electron correlation are critical to understanding the photochemical mechanism. PMID- 26679299 TI - Impact of omalizumab therapy on medication requirements for chronic rhinosinusitis. AB - BACKGROUND: Omalizumab is indicated for treatment of patients with moderate to severe allergic asthma. Previous studies have shown 70% of these patients also have chronic rhinosinusitis (CRS). The present series examines the impact of omalizumab on medication use for CRS in a cohort of asthmatic CRS patients who received this therapy. METHODS: The sample included 25 patients with adequate prescription data preinitiation and postinitiation of therapy. Data was available for a full 12 months both preinitiation and postinitiation of therapy in 20 of 25 patients and for 4 to 8 months in the remaining 5 of 25. Average antibiotic use (# of unique prescriptions per month) and systemic steroid dose (mg/month) were tabulated for each patient and compared before and after initiation of therapy. RESULTS: Mean antibiotic prescriptions/month decreased by 37%, and this was statistically significant (p = 0.013). Antibiotic use decreased in 15 of 25 (60%), was the same in 7 of 25 (28%), and increased in 3 of 25 (12%) patients. Chronic steroid administration was required in 19 of 25 patients, and dosing was highly variable. Mean monthly steroid dose decreased substantially in 8 of 19 (42%) patients, with reduction ranging from 40% to 100% from pretreatment levels. A modest decrease of 17% to 30% was observed in 4 of 19 (21%) patients. Steroid use was essentially unchanged in 4 of 19 (21%), but dramatically increased (71% to 366% above pretreatment dose) in 3 of 19 (15%) patients. CONCLUSION: Omalizumab therapy is associated with a decrease in overall antibiotic use for CRS. A subset of patients also experience significant reduction in steroid dependence. Further study is necessary to determine factors predictive of response. PMID- 26679301 TI - [Current Strategies for Promoting the Transfer of Lifestyle Changes into Everyday Living and Improving Sustainability]. PMID- 26679302 TI - The Power of (But Not In?) Sexual Configurations Theory. PMID- 26679300 TI - KillerOrange, a Genetically Encoded Photosensitizer Activated by Blue and Green Light. AB - Genetically encoded photosensitizers, proteins that produce reactive oxygen species when illuminated with visible light, are increasingly used as optogenetic tools. Their applications range from ablation of specific cell populations to precise optical inactivation of cellular proteins. Here, we report an orange mutant of red fluorescent protein KillerRed that becomes toxic when illuminated with blue or green light. This new protein, KillerOrange, carries a tryptophan based chromophore that is novel for photosensitizers. We show that KillerOrange can be used simultaneously and independently from KillerRed in both bacterial and mammalian cells offering chromatic orthogonality for light-activated toxicity. PMID- 26679304 TI - Assessing Police Classifications of Sexual Assault Reports: A Meta-Analysis of False Reporting Rates. AB - The objective of the study was to determine, through meta-analysis, the rate of confirmed false reports of sexual assault to police. The meta-analysis initially involved a search for relevant articles. The search identified seven studies where researchers or their trained helpers evaluated reported sexual assault cases to determine the rate of confirmed false reports. The meta-analysis calculated an overall rate and tested for possible moderators of effect size. The meta-analytic rate of false reports of sexual assault was .052 (95 % CI .030, .089). The rates for the individual studies were heterogeneous, suggesting the possibility of moderators of rate. However, the four possible moderators examined year of publication, whether the data set used had information in addition to police reports, whether the study was completed in the U.S. or elsewhere, and whether inter-rater reliabilities were reported-were all not significant. The meta-analysis of seven relevant studies shows that confirmed false allegations of sexual assault made to police occur at a significant rate. The total false reporting rate, including both confirmed and equivocal cases, would be greater than the 5 % rate found here. PMID- 26679303 TI - Sexual Stigma, Coping Styles, and Psychological Distress: A Longitudinal Study of Men Who Have Sex With Men in Beijing, China. AB - The direct link between stigma against sexual minorities and psychological distress is well established. However, few studies have examined the potential mediating roles of avoidant and social support coping in the relationships between internalized and anticipated stigma associated with homosexuality and depressive symptoms and anxiety among Chinese men who have sex with men (MSM). We recruited a longitudinal sample of 493 MSM in Beijing, China from 2011 to 2012. Participants completed computer-based questionnaires at baseline, 6, and 12 months. We found significant indirect effects of anticipated MSM stigma on symptoms of both depression and anxiety via avoidant coping: anticipated MSM stigma at baseline was significantly associated with avoidant coping (B = 0.523, p < 0.001) at 6 months and, conditional on anticipated MSM stigma, avoidant coping had a significant positive effect on depressive symptoms and anxiety at 12 months (B = 0.069, p = 0.001 and B = 0.071, p = 0.014). In contrast, no significant indirect effects of anticipated MSM stigma on either psychological distress outcome via social support coping were found. No significant indirect effects of internalized MSM stigma via either avoidant or social support coping were found. These results underscore the need for interventions that address anticipations of stigma and the use of avoidant coping techniques to manage such anticipations. PMID- 26679305 TI - Monogamy versus Consensual Non-Monogamy: Alternative Approaches to Pursuing a Strategically Pluralistic Mating Strategy. AB - This study examined the frequency of partner-directed mate retention behaviors and several self- and partner-rated romantic relationship evaluations (i.e., sociosexuality, relationship satisfaction, mate value, and partner ideal measures) within monogamous and consensually non-monogamous (CNM) relationships. Measures were compared (1) between monogamous and CNM participants and (2) between two concurrent partners within each CNM relationship (i.e., primary and secondary partners). We found that individuals in currently monogamous relationships (n = 123) performed more mate retention behaviors compared to those currently in CNM relationships (n = 76). Within CNM relationships, participants reported engaging in more mate retention behaviors with primary partners compared to secondary partners. Likewise, CNM participants reported talking about their extra-dyadic sexual experiences and downplaying these sexual experiences more often with their primary partner compared to their secondary partner. There were no significant differences between ratings of monogamous and primary partners in participants' overall relationship satisfaction. However, monogamous participants reported less satisfaction with the amount of communication and openness they had with their partner compared to CNM participants' reports of their primary partner, but not secondary partner. By comparison, CNM participants reported higher overall relationship satisfaction with primary compared to secondary partners and considered their primary partner to be more desirable as a long-term mate than their secondary partner. We interpret these results within the context of previous research on monogamous and CNM relationships and hypothesize that these relationship configurations are alternative strategies for pursuing a strategically pluralistic mating strategy. PMID- 26679306 TI - [In Process Citation]. PMID- 26679307 TI - [In Process Citation]. PMID- 26679308 TI - [In Process Citation]. PMID- 26679309 TI - [In Process Citation]. PMID- 26679310 TI - [In Process Citation]. PMID- 26679311 TI - End-of-life decisions in perinatal care: A view from health-care providers in Mexico. AB - OBJECTIVE: To examine the opinions of a perinatal health team regarding decisions related to late termination of pregnancy and severely ill newborns. MATERIALS AND METHODS: An anonymous questionnaire was administered to physicians, social workers, and nurses in perinatal care. Differences were evaluated using the chi square and Student's t tests. RESULTS: When considering severely ill fetuses and newborns, 82% and 93% of participants, respectively, opted for providing palliative care, whereas 18% considered feticide as an alternative. Those who opted for palliative care aimed to diminish suffering and those who opted for intensive care intended to protect life or sanctity of life. There was poor knowledge about the laws that regulate these decisions. CONCLUSIONS: Although there is no consensus on what decisions should be taken with severely ill fetuses or neonates, most participants considered palliative care as the first option, but feticide or induced neonatal death was not ruled out. PMID- 26679312 TI - Conformance contrast testing between rates of pulmonary tuberculosis in Ecuadorian border areas. AB - OBJECTIVE: To estimate rates of cases of respiratory symptomatic subjects and the incidence rate of pulmonary tuberculosis in two border areas of Ecuador, and contrast them with official figures. MATERIALS AND METHODS: Cross-sectional survey in the southeastern (SEBA), and the Andean southern Ecuadorian border areas (ASBA), which were conducted, respectively, in 1 598 and 2 419 persons aged over 15 years recruited over periods of three weeks. In identified respiratory symptomatic cases, a sputum sample was taken for smear testing. The results (odds ratios and their respective 95% confidence intervals), were compared with local and national official figures using maximum likelihood contrasts. RESULTS: The rates of respiratory symptomatic subjects (7.7% and 5.9% in the SEBA, and ASBA, respectively) and of pulmonary tuberculosis (cumulative incidence rates of 125 and 140 per 100 000 inhabitants, in the same order) were significantly greater than the official figures (of 0.98 and 0.99% for respiratory symptomatic subjects in the SEBA and ASBA, respectively; and of 38.23 per 100 000 inhabitants for pulmonary tuberculosis in Ecuador as a whole) (p<0.001). CONCLUSION: It is necessary to reinforce both active case finding for respiratory symptomatic subject cases, and epidemiological surveillance of pulmonary tuberculosis in Ecuadorian border regions. PMID- 26679313 TI - [Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model]. AB - OBJECTIVE: To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. MATERIALS AND METHODS: A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. RESULTS: Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. CONCLUSIONS: Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained. PMID- 26679314 TI - Inter-rater reliability of measures to characterize the tobacco retail environment in Mexico. AB - OBJECTIVE: To evaluate the inter-rater reliability of a data collection instrument to assess the tobacco retail environment in Mexico, after major marketing regulations were implemented. MATERIALS AND METHODS: In 2013, two data collectors independently evaluated 21 stores in two census tracts, through a data collection instrument that assessed the presence of price promotions, whether single cigarettes were sold, the number of visible advertisements, the presence of signage prohibiting the sale of cigarettes to minors, and characteristics of cigarette pack displays. We evaluated the inter-rater reliability of the collected data, through the calculation of metrics such as intraclass correlation coefficient, percent agreement, Cohen's kappa and Krippendorff's alpha. RESULTS: Most measures demonstrated substantial or perfect inter-rater reliability. CONCLUSIONS: Our results indicate the potential utility of the data collection instrument for future point-of-sale research. PMID- 26679315 TI - [Brucellosis, a zoonotic disease present in the population: A time series study in Mexico]. AB - OBJECTIVE: To determinate the relationship of human brucellosis incidence in Mexico during 2000-2011 in relation with domestic ruminant brucellosis. MATERIALS AND METHODS: An ecological time series study was analyzed using multilevel poisson multiple regression, the incidence of human brucellosis during 2000-2011 and incidence in ruminants and human development index. RESULTS: The high incidence of bovine brucellosis increased 19% the incidence of human brucellosis. The high incidence of caprine brucellosis increase 17% the incidence of human brucellosis. The presence of new cases of ovine brucellosis increased 13% the incidence rates of human brucellosis. CONCLUSIONS: Brucellosis is a public health problem in Mexico, the presence of brucellosis in domestic ruminants and the level of disease control in them affects the presence of the disease in humans. PMID- 26679316 TI - [Organizational climate in management teams and its relationship with health care outcomes]. AB - OBJECTIVE: To identify the relationship between organizational climate of management teams and the performance of health services. MATERIALS AND METHODS: A transversal and analytical study was designed. The Organizational Climate Scale (OCS) was utilized and performance was assessed by the achievement indicators through correlation analysis and multiple regression. Thirty four medical benefits services headquarters (JSPM) were measured of the Mexican Social Security Institute. RESULTS: Of 862 participating, 238 (27.6%) evaluated the climate of their organizations with a high level; the maximal score was 56%. Average performance value was 0.79 +/- 0.07 (minimal: 0.65; maximal: 0.92). A positive correlation was demonstrated between organizational climate level and performance (r=0.4; p=0.008). CONCLUSIONS: The organizational climate of the health services managers (JSPM) is directly related with performance in health care. PMID- 26679317 TI - [Therapeutic adherence to retraining programs for women and men involved in abusive relationships in Mexico]. AB - OBJECTIVE: To analyze the therapeutic adherence among participants in the retraining program operated by the Ministry of Health of Mexico, in eight states in 2010. MATERIALS AND METHODS: This is a cross-sectional and descriptive study that assesses therapeutic adherence in a retraining intervention program for male perpetrators and female victims of intimate partner violence. The intervention was coordinated by a team of previously trained professionals. The selection of participants was made by means of a specific screening test. Overall performance for both groups was analyzed, and based on the attendance they were classified in low adhesion (1-12) medium to high (13 and>). To determine the possibility of adhesion, Student's t tests, a bivariate analysis, and a logistic regression model were performed for each program. RESULTS: 5 539 screenings were applied, of which 88.3% (n = 4 891) were positive. 85% agreed to participate (n = 4 151), but only 75% of potential participants attended at least one session (n = 3 022). 78.5% attended between 1-12 sessions. In the women's program, significant differences in marital status, religion and age groups (p<0.05) were found. In the program for men, significant differences in religion and age groups (p<0.05) were found. CONCLUSIONS: In the Mexican context there are few studies that assess adherence to programs of care and retraining for partner violence. This study is a first approach that opens the possibility to enhance the design and evaluation of such interventions, which are crucial to dismantle violence against women. PMID- 26679318 TI - [Challenges in the implementation of clinical practice guidelines in major public health institutions in Mexico: A multiple case study]. AB - OBJECTIVE: To identify, prioritize and relate barriers and facilitators in the implementation of Clinical Practice Guidelines (GPC, in Spanish). MATERIALS AND METHODS: We used qualitative methods to study and compare the introduction of GPC across the domains of the consolidated research implementation framework in hospitals of the three main public institutions in a state of Mexico. Authorities and hospital staff were interviewed using a semi-structured questionnaire. RESULTS: The main barriers to implementation are the absence of standards, training, resources and incentives. The most important implementation facilitators are the characteristics of the GPC, which are perceived as properly designed and with simple language as well as with capacity to improve the work environment. CONCLUSION: The barriers to implementation must be solved to achieve the goal of standardizing the healthcare process across the sector; the positive perception of the GPC should promote the continuous actualization of the evidence and a sectoral view from their development stage to ensure adoption in the heterogeneous environments that characterize health institutions. PMID- 26679319 TI - [Evolution of the theory and practices for the control of vector borne diseases]. AB - The conceptual models of the public health have bonds with the advance in the knowledge of the VBDs. The establishment of the colonial empires, the sprouting of great scale sanitary interventions, the creation of tie international organisms dedicated to the promotion of the health, the participation of phylantropic institutions financing and organizing different health campaigns are only a few contributions to the field. This body of knowledge contributed to the birth and the progress of several medical disciplines, academic institutions and international organisms dedicated to the education of human resources, research and health services; establishing the production and reproduction bases of this intellectual field. The way that VBDs have been faced has also molded great part of the ideas and the practices in Public Health and its essence has been adopted to elaborate the prevention and control programs of other many problems of health. PMID- 26679320 TI - [Afterschool physical activity programs: Literature review]. AB - The purpose of this review was to analyze the scientific production about extra curricular physical activity (PA) in western children of 6-12 years. Medline / Pub-Med, Scopus and Google Scholar were used. This search collects articles published between January 1990 and May 2013. A total of 104 publications were analyzed. The body composition parameters are best used to assess the results of the studies, followed by those which estimate the maximum aerobic capacity. Articles of intervention are presented with very heterogeneous methodological features but there are clear trends in the use of certain aspects. As for the reviews, most are systematic and include meta-analysis. In this studies, body mass index (BMI) is the most used parameter. PMID- 26679321 TI - [Who counts in public health? (Counting births and deaths)]. PMID- 26679322 TI - Arsenic Uptake and Accumulation in Okra (Abelmoschus esculentus) as Affected by Different Arsenical Speciation. AB - Experimental investigations were conducted to evaluate the toxic effects of different arsenic (As) species such as arsenite (As(III)), arsenate (As(V)) and dimethylarsinic acid (DMA) on the growth of okra (Abelmoschus esculentus). The present study describes the changes in the growth, yield and accumulation characteristics of okra plants spiked with 20 and 50 mg kg(-1) of As(III), As(V) and DMA. As species negatively affected the yield and growth of the plant.The availability of arsenic compounds in the aerial parts decreased in the order As(V) > As(III) > DMA and in the roots observed as As(III) > As(V) > DMA. The results showed that except As(V), okra accumulated As(III) and DMA mainly in its roots with limited transport to shoots. Thus the plant has the capacity to tolerate As stress and can be considered as a resistive variety. The study also reveals that removal of As by boiling the vegetables with excess of water is not possible. PMID- 26679323 TI - Assessment of Constructed Wetland in Nutrient Reduction, in the Commercial Scale Experiment Ponds of Freshwater Prawn Macrobrachium rosenbergii. AB - A free water surface constructed wetland (CW) was integrated into two commercial ponds of Macrobrachium rosenbergii, to evaluate the role of CW in reducing the excess nutrient concentration and other pollutants produced from the aquaculture waste. Hydraulic residence time was kept constant (24 h). There was a significant (p < 0.05) decrease in total suspended solids (TSS, 73.2 +/- 15.4 %) and total nitrogen (TN, 39.6 +/- 44.2 %) between wetland inflow and wetland outflow. The performance of the CW was highly impacted by the low concentration of dissolved nutrients at the inflow of CW. Results showed about 43.8 +/- 24.6 % NO3 (-), 25.7 +/- 23.0 % NH4 (+), 14.3 +/- 1.0 % NO2 (-), 28.4 +/- 18.8 % DIN and 13.1 +/- 10.0 % PO4 (3-) were removed. In agreement with previous published investigations, comparing values of pollutants before and after recirculation, this study concludes that a CW system can provide good water quality and minimize external water input. PMID- 26679324 TI - Bisphenol A in Urine of Chinese Young Adults: Concentrations and Sources of Exposure. AB - Bisphenol A (BPA) is an endocrine disrupting environmental chemical. Urinary concentrations of BPA were measured in samples collected nationwide from Chinese young adults. The geometric mean urinary concentration of BPA in Chinese young adults was 2.23 ng/mL. The estimated daily exposure dose for BPA was 64.8 ng/kg bw/day. Contributions of various BPA sources to exposure in Chinese young adults were estimated. Dietary intake was the primary exposure pathway. The contribution of dietary intake, indoor dust, paper products and personal care products to BPA intake was 72.5 %, 0.74 %, 0.98 %, 0.22 % of the total exposure dose, respectively. This is the first study on the occurrence of BPA in young adults from most provinces and autonomous regions of China. The results can be used to establish a database for BPA exposure assessment for Chinese general population. PMID- 26679325 TI - Distribution and Speciation of Cu in the Root Border Cells of Rice by STXM Combined with NEXAFS. AB - Root border cells (RBCs) serve plants in their initial line of defense against stress from the presence of heavy metals in the soil. In this research, light microscopy and synchrotron-based scanning transmission X-ray microscopy (STXM) combined with near edge X-ray absorption fine structure spectroscopy (NEXAFS) with a nanoscale spatial resolution were used to investigate the effects of copper (Cu) upon the RBCs, as well as its distribution and speciation within the RBCs of rice (Oryza sativa L.) under aeroponic culture. The results indicated that with increasing exposure time and concentration, the attached RBCs were surrounded by a thick mucilage layer which changed in form from an ellipse into a strip in response to Cu ion stress. Copper was present as Cu(II), which accumulated not only in the cell wall but also in the cytoplasm. To our knowledge, this is the first time that STXM has been used in combination with NEXAFS to provide new insight into the distribution and speciation of metal elements in isolated plant cells. PMID- 26679326 TI - Comparing multiple imputation methods for systematically missing subject-level data. AB - When conducting research synthesis, the collection of studies that will be combined often do not measure the same set of variables, which creates missing data. When the studies to combine are longitudinal, missing data can occur on the observation-level (time-varying) or the subject-level (non-time-varying). Traditionally, the focus of missing data methods for longitudinal data has been on missing observation-level variables. In this paper, we focus on missing subject-level variables and compare two multiple imputation approaches: a joint modeling approach and a sequential conditional modeling approach. We find the joint modeling approach to be preferable to the sequential conditional approach, except when the covariance structure of the repeated outcome for each individual has homogenous variance and exchangeable correlation. Specifically, the regression coefficient estimates from an analysis incorporating imputed values based on the sequential conditional method are attenuated and less efficient than those from the joint method. Remarkably, the estimates from the sequential conditional method are often less efficient than a complete case analysis, which, in the context of research synthesis, implies that we lose efficiency by combining studies. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26679327 TI - Detecting and interpreting conscious experiences in behaviorally non-responsive patients. AB - Decoding the contents of consciousness from brain activity is one of the most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. The lack of consistent behavioral responsivity engenders unique challenges to decoding any conscious experiences these patients may have solely based on their brain activity. For this reason, paradigms that have been successful in healthy individuals cannot serve to interpret conscious mental states in this patient group. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command, in order to decode the presence of willful brain-based responses in this patient group. In recent work, we have used naturalistic paradigms, such as watching a movie or listening to an audio-story, to demonstrate that a common neural code supports conscious experiences in different individuals. Moreover, we have demonstrated that this code can be used to interpret the conscious experiences of a patient who had remained non-responsive for several years. This approach is easy to administer, brief, and does not require compliance with task instructions. Rather, it engages attention naturally through meaningful stimuli that are similar to the real-world sensory information in a patient's environment. Therefore, it may be particularly suited to probing consciousness and revealing residual brain function in highly impaired, acute, patients in a comatose state, thus helping to improve diagnostication and prognostication for this vulnerable patient group from the critical early stages of severe brain injury. PMID- 26679328 TI - MUSE: MUlti-atlas region Segmentation utilizing Ensembles of registration algorithms and parameters, and locally optimal atlas selection. AB - Atlas-based automated anatomical labeling is a fundamental tool in medical image segmentation, as it defines regions of interest for subsequent analysis of structural and functional image data. The extensive investigation of multi-atlas warping and fusion techniques over the past 5 or more years has clearly demonstrated the advantages of consensus-based segmentation. However, the common approach is to use multiple atlases with a single registration method and parameter set, which is not necessarily optimal for every individual scan, anatomical region, and problem/data-type. Different registration criteria and parameter sets yield different solutions, each providing complementary information. Herein, we present a consensus labeling framework that generates a broad ensemble of labeled atlases in target image space via the use of several warping algorithms, regularization parameters, and atlases. The label fusion integrates two complementary sources of information: a local similarity ranking to select locally optimal atlases and a boundary modulation term to refine the segmentation consistently with the target image's intensity profile. The ensemble approach consistently outperforms segmentations using individual warping methods alone, achieving high accuracy on several benchmark datasets. The MUSE methodology has been used for processing thousands of scans from various datasets, producing robust and consistent results. MUSE is publicly available both as a downloadable software package, and as an application that can be run on the CBICA Image Processing Portal (https://ipp.cbica.upenn.edu), a web based platform for remote processing of medical images. PMID- 26679329 TI - Keto analogue and amino acid supplementation and its effects on ammonemia and performance under thermoneutral conditions. AB - Alterations of cerebral function, fatigue and disturbance in cognitive-motor performance can be caused by hyperammonemia and/or hot environmental conditions during exercise. Exercise-induced hyperammonemia can be reduced through supplementation with either amino acids or combined keto analogues and amino acids (KAAA) to improve exercise tolerance. In the present study, we evaluated KAAA supplementation on ammonia metabolism and cognitive-motor performance after high-intensity exercise under a low heat stress environment. Sixteen male cyclists received a ketogenic diet for 2 d and were divided into two groups, KAAA (KEx) or placebo (CEx) supplementation. The athletes performed a 2 h cycling session followed by a maximum test (MAX), and blood samples were obtained at rest and during exercise. Cognitive-motor tasks were performed before and after the protocol, and the exhaustion time was used to evaluate physical performance. The hydration status was also evaluated. The CEx group showed a significant increase (~ 70%) in ammonia concentration at MAX, which did not change in the KEx group. The non-supplemented group showed a significant increase in uremia. Both the groups had a significant increase in blood urate concentrations at 120 min, and an early significant increase from 120 min was observed in the CEx group. There was no change in the glucose concentrations of the two groups. A significant increase in lactate was observed at the MAX moment in both groups. There was no significant difference in the exhaustion times between the groups. No changes were observed in the cognitive-motor tasks after the protocol. We suggest that KAAA supplementation decreases ammonia concentration during high-intensity exercise but does not affect physical or cognitive-motor performances under a low heat stress environment. PMID- 26679330 TI - WATER FLUORIDATION: SAFETY, EFFECTIVENESS AND VALUE IN ORAL HEALTH: A SYMPOSIUM AT THE 2014 ANNUAL MEETING OF THE AMERICAN AND CANADIAN ASSOCIATIONS FOR DENTAL RESEARCH. PMID- 26679331 TI - PHARMACOTHERAPY FOR THE ELDERLY DENTAL PATIENT. AB - Current demographic data clearly show that the North American population is aging, and projections suggest that the percentage of older people will increase. The elderly often suffer from multiple chronic conditions that affect their quality of life, use of health services, morbidity and mortality. Also, in those of advanced age, the pharmacokinetics and pharmacodynamics of many drugs are altered. Polypharmacy increases the incidence of adverse drug reactions and drug interactions in this population. Thus, the dentist must be continually aware of the pharmacologic status of each patient and consider the likelihood of interactions between drugs prescribed by the dentist, drugs prescribed by the physician and drugs that are self-administered, including over-the-counter medications and natural supplements. In this article, we discuss pharmacokinetic and pharmacodynamic changes in the elderly patient, polypharmacy and the changes in prescribing for our dental patients. Specific emphasis is placed on the drugs commonly prescribed by dentists: local anesthetics, analgesics and antibiotics. PMID- 26679332 TI - ORAL HEALTH RESEARCH METHODS SUMMER INSTITUTE: A SYSTEMATIC REVIEW METHODOLOGY WORKSHOP. PMID- 26679333 TI - OSTEONECROSIS OF THE JAW: AN UPDATE FOR DENTISTS. PMID- 26679334 TI - MANAGEMENT OF DENTAL EXTRACTIONS IN PATIENTS TAKING WARFARIN AS ANTICOAGULANT TREATMENT: A SYSTEMATIC REVIEW. AB - OBJECTIVES: The management of patients on anticoagulation therapy is challenging. The objective of this study was to conduct a systematic review to establish the effectiveness of hemostatic interventions to prevent postoperative bleeding following dental extractions among patients taking warfarin. METHODS: A systematic review of the literature was conducted using PubMed, EMBASE and the Cochrane Central Register of Controlled Trials databases and applying relevant MeSH terms. Identified studies were screened independently by 2 reviewers using the following selection criteria: tooth extraction, patients taking warfarin as the only anticoagulant, randomized controlled trials and a hemostatic intervention. RESULTS: Six articles were included in the final review, all evaluating different interventions. Oral or local hemostatic agents were compared in 4 studies where patients continued taking warfarin before and after the procedure; in 3 studies, there were no differences between the agents in preventing postoperative bleeding and, in 1, Histoacryl glue was superior to a gelatin sponge. Two studies compared warfarin continuation with temporary discontinuation and found that continuation did not increase the risk of bleeding in patients who had an international normalized ratio (INR) within the therapeutic range. CONCLUSIONS: Patients with an INR within the therapeutic range can safely continue taking the regular dose of warfarin before dental extractions. There is no evidence to support or reject the superiority of local hemostatic agents over warfarin discontinuation. PMID- 26679335 TI - DENTISTS' PERSPECTIVES ON THE MANITOBA DENTAL ASSOCIATION'S FREE FIRST VISIT PROGRAM. AB - BACKGROUND: In 2010, the Manitoba Dental Association implemented the Free First Visit (FFV) program to provide access to dental screenings for children under 3 years of age and promote the concept of the age 1 dental visit. In this article, we report on dentists' views of the program. METHODS: This qualitative study included 3 focus groups held in Winnipeg, Canada. An interview guide was developed to structure discussions. RESULTS: Thirty dentists participated. They were extremely supportive of the FFV program and its continuation. Promoting early visits and providing parents with anticipatory guidance were some reasons dentists participated. The most common reason for not participating was that dentists were already providing free dental care for children. Dentists viewed the goals of the program as increasing public awareness of the importance of early dental visits, establishing dental homes, educating parents, identifying early signs of caries and increasing children's level of comfort in the dental clinic. They indicated that the FFV program prompted some parents to take their children earlier than they might have otherwise. They said that most FFVs were provided to families who were already part of their practice. According to participating dentists, most parents were unaware of the FFV program and did not know about the age 1 visit recommendation. Dentists recommended that the FFV program concentrate on promoting the first visit by age 1 message with the free component as a secondary message. Participants recommended increasing general dentists' involvement in the program as most FFVs are currently provided by pediatric dentists. CONCLUSIONS: Most dentists participating in this study were supportive of the FFV program and advocated its continuation in Manitoba. PMID- 26679336 TI - IS GUTTACORE MORE EASILY REMOVED FROM THE ROOT CANAL THAN THERMAFIL? AN EX-VIVO STUDY. AB - GuttaCore is a new cross-linked gutta-percha carrier. Its handling time and ease of removal were compared with those of a plastic carrier (Thermafil) and the continuous wave of condensation technique (control). Forty-five maxillary central incisors were randomly divided 3 groups according to filling technique and retreatment was carried out in all samples with NiTi rotary files, hand files and ultrasonic inserts. Time required for filling removal was recorded. Roots were then split longitudinally and photographed under 5x magnification, and residual filling material was quantified. Removal time was significantly longer for Thermafil (7.10 minutes) than GuttaCore (2.91 minutes) and the control group (1.93 minutes) (p < 0.001). The amount of residual filling material did not differ among the groups: Thermafil 8.31%, GuttaCore 6.27 and control 8.68% (p > 0.05). In conclusion, replacing plastic core with cross-linked gutta-percha allows easier removal of carrier from the root canal. The remnants of filling material in all samples illustrate that retreatment remains a challenge in endodontics. PMID- 26679338 TI - HOW DO I MANAGE A PATIENT WITH A FRACTURED PORCELAIN VENEER? PMID- 26679337 TI - DENTAL STUDENTS' PERSPECTIVES ON RURAL DENTAL PRACTICE: A QUALITATIVE STUDY. AB - INTRODUCTION: The chronic shortage of dentists in rural communities may affect the quality of care provided to these communities. The aim of this study was to explore the knowledge and perspectives of Quebec's future dentists regarding rural dental practice and their career intentions. METHODS: We conducted a qualitative study at 2 major dental faculties using the interpretive description method. Purposeful maximum variation sampling and snowball techniques were used to recruit 4th-year dental students and specialty residents as study participants. Face-to-face, semi-structured, 60-90-minute interviews were conducted and audio-recorded. Qualitative data were analyzed using a thematic approach including interview debriefing, transcript coding, data display and interpretation. RESULTS: Of the 17 interviews, 10 were with women and 7 with men; the age range of participants was 22-39 years. Five major themes emerged from the interviews: awareness of access to oral health care in rural areas, image of rurality, image of rural dental practice, perceived barriers to and perceived enablers of rural dental practice. Students said that undergraduate dental education, financial rewards, professionalism, professional support and social media may positively affect their perspective on rural dental practice. CONCLUSIONS: There is a need to implement and support strategies known to increase dental students' knowledge of rural practice and their motivation to choose rural practice. Dental educators have an essential role to play in shaping professional character and encouraging apprenticeship to meet these goals. PMID- 26679339 TI - Women's experiences of transfer from primary maternity unit to tertiary hospital in New Zealand: part of the prospective cohort Evaluating Maternity Units study. AB - BACKGROUND: There is worldwide debate regarding the appropriateness and safety of different birthplaces for well women. The Evaluating Maternity Units (EMU) study's primary objective was to compare clinical outcomes for well women intending to give birth in either a tertiary level maternity hospital or a freestanding primary level maternity unit. Little is known about how women experience having to change their birthplace plans during the antenatal period or before admission to a primary unit, or transfer following admission. This paper describes and explores women's experience of these changes-a secondary aim of the EMU study. METHODS: This paper utilised the six week postpartum survey data, from the 174 women from the primary unit cohort affected by birthplace plan change or transfer (response rate 73%). Data were analysed using descriptive statistics and thematic analysis. The study was undertaken in Christchurch, New Zealand, which has an obstetric-led tertiary maternity hospital and four freestanding midwife led primary maternity units (2010-2012). The 702 study participants were well, pregnant women booked to give birth in one of these facilities, all of whom received continuity of midwifery care, regardless of their intended or actual birthplace. RESULTS: Of the women who had to change their planned place of birth or transfer the greatest proportion of women rated themselves on a Likert scale as unbothered by the move (38.6%); 8.8% were 'very unhappy' and 7.6% 'very happy' (quantitative analysis). Four themes were identified, using thematic analysis, from the open ended survey responses of those who experienced transfer: 'not to plan', control, communication and 'my midwife'. An interplay between the themes created a cumulatively positive or negative effect on their experience. Women's experience of transfer in labour was generally positive, and none expressed stress or trauma with transfer. CONCLUSIONS: The women knew of the potential for change or transfer, although it was not wanted or planned. When they maintained a sense control, experienced effective communication with caregivers, and support and information from their midwife, the transfer did not appear to be experienced negatively. The model of continuity of midwifery care in New Zealand appeared to mitigate the negative aspects of women's experience of transfer and facilitate positive birth experiences. PMID- 26679340 TI - Evolution of IgA nephropathy into anaphylactoid purpura in six cases--further evidence that IgA nephropathy and Henoch-Schonlein purpura nephritis share common pathogenesis. AB - BACKGROUND: As the morphological and immunohistochemical manifestations of immunoglobulin A (IgA) nephropathy and Henoch-Schonlein purpura nephritis (HSPN) are very similar, they are considered to share a common pathogenesis. Although HSPN usually develops after the appearance of anaphylactoid purpura, we have encountered patients whose renal symptoms preceded purpura. METHODS: We reviewed the clinical courses of patients who were first diagnosed with IgA nephropathy, but developed purpura later, at the National Center for Child Health and Development in Tokyo, Japan. RESULTS: Of the 53 patients who were diagnosed with primary IgA nephropathy at our institute during the study period (March 2002 to July 2015), six (11 %) developed anaphylactoid purpura after the diagnosis of primary IgA nephropathy and therefore met the inclusion criteria. Duration between the onset of nephritis and subsequent appearance of purpura ranged from 5 months to 14 years. One patient reached end-stage renal failure due to IgA nephropathy and developed purpura after renal transplantation. All renal biopsies performed before the appearance of purpura showed mesangial proliferation with predominant IgA deposits. Urinary findings deteriorated in three patients after the appearance of purpura, including one patient who developed rapidly progressive glomerulonephritis. Renal biopsy findings worsened in two patients. At the last observation, two patients showed mild renal insufficiency. CONCLUSIONS: Our clinical experience and previous reports support the argument that IgA nephropathy and HSPN are different manifestations of a single disease. Hence, it is acceptable to consider that they are variants of a single disease. PMID- 26679341 TI - 1,25-Dihydroxyvitamin D3 Protects against Immune-Mediated Killing of Neurons in Culture and in Experimental Autoimmune Encephalomyelitis. AB - Several studies have reported that low vitamin D levels are associated with an increased risk of developing multiple sclerosis (MS). As MS is an inflammatory disorder with degeneration of axons and neurons, we examined whether the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), could protect against the T cell-mediated killing of human neurons in culture, and the axonal loss seen in mice with experimental autoimmune encephalomyelitis (EAE). Human neurons were exposed to activated human T lymphocytes and the loss of neurons was documented 24 hours later by counting the number of microtubule associated protein-2 positive cells. Mice with EAE were harvested for counts of axonal profiles in the spinal cord. 1,25D3 was exposed to T cells in culture or administered to mice from peak EAE clinical severity when axonal loss was already evolving. Activated T lymphocytes killed human neurons prominently within 24 hours but toxicity was significantly attenuated when T cells were exposed to 1,25D3 prior to the co-culture. In EAE, 1,25D3 treatment initiated from peak clinical severity reduced the extent of clinical disability and mitigated the progressive loss of axons. The reduction of axonal and neuronal loss by 1,25D3 in the context of an inflammatory assault to the central nervous system is a potential contributor to the putative benefits of vitamin D in MS. PMID- 26679342 TI - In situ marker-based assessment of leaf trait evolutionary potential in a marginal European beech population. AB - Evolutionary processes are expected to be crucial for the adaptation of natural populations to environmental changes. In particular, the capacity of rear edge populations to evolve in response to the species limiting conditions remains a major issue that requires to address their evolutionary potential. In situ quantitative genetic studies based on molecular markers offer the possibility to estimate evolutionary potentials manipulating neither the environment nor the individuals on which phenotypes are measured. The goal of this study was to estimate heritability and genetic correlations of a suite of leaf functional traits involved in climate adaptation for a natural population of the tree Fagus sylvatica, growing at the rear edge of the species range. Using two marker-based quantitative genetics approaches, we obtained consistent and significant estimates of heritability for leaf phenological (phenology of leaf flush), morphological (mass, area, ratio mass/area) and physiological (delta(13)C, nitrogen content) traits. Moreover, we found only one significant positive genetic correlation between leaf area and leaf mass, which likely reflected mechanical constraints. We conclude first that the studied population has considerable genetic diversity for important ecophysiological traits regarding drought adaptation and, second, that genetic correlations are not likely to impose strong genetic constraints to future population evolution. Our results bring important insights into the question of the capacity of rear edge populations to evolve. PMID- 26679343 TI - Comparison of miniaturized percutaneous nephrolithotomy and flexible ureterorenoscopy for the management of 10-20 mm renal stones in obese patients. AB - PURPOSE: To evaluate and compare effectivity and safety of flexible ureteroscopy (F-URS) and mini-percutaneous nephrolithotomy (mPNL) for 10-20 mm renal stones in obese patients. METHODS: Between 2012 and 2015, charts of patients who were treated with F-URS or mPNL for 10-20 mm kidney stone(s) were analyzed. Patients with BMI > 30 kg/m(2) were enrolled into the study. Total of 315 patients were treated with mPNL, and 56 patients were matched our inclusion criteria. In the same period, F-URS was performed in 669 patients, and 157 of them had 10-20 mm kidney stones, and their BMI values were >30 kg/m(2). The patients were retrospectively matched at a 1:1 ratio to index F-URS-mPNL cases with respect to the patient age, gender, ASA score, BMI and size, number, and location of stone. RESULTS: Gender, age, BMI, stone size, stone number, location of stone(s), and ASA scores were similar between groups. The mean operation time was significantly longer in mPNL group (p: 0.021). However, the mean fluoroscopy time was similar (p: 0.270). Hemoglobin drop requiring blood transfusion and angioembolization was performed in two and one patients after mPNL, respectively. Overall complication rate was significantly higher in mPNL group than F-URS group (30.3 vs. 5.3 %, p: 0.001). CONCLUSION: Our results demonstrated that both F-URS and mPNL achieve acceptable stone-free rates in obese patients with 10-20 mm renal stones. However, complication rates were significantly lower in F-URS group. PMID- 26679345 TI - Associations between toddlers' and parents' BMI, in relation to family socio demography: a cross-sectional study. AB - BACKGROUND: It is well established that the pregnancy and the first years of life are important for future childhood health and body weight. Even though current evidence suggests that both parents are important for childhood health, the influence that parents' BMI and socio-demography has on toddlers' BMI has so far received little attention. This study aimed to increase our knowledge on the association between toddlers' and parents' BMI, in relation to family socio demography. Further, the aim was to investigate the interaction between the mothers' and fathers' BMI in relation to their child's BMI. METHODS: A total of 697 children with a median age of 18 months (range 16-24 months) participated in the study along with their mothers (n = 697) and fathers (n = 674). As regards representability, our parental sample had a lower proportion of immigrants and the parents were more gainfully employed compared to parents in the rest of Sweden (when the child was 18 months old). The parents completed a questionnaire on parental and child health. Data on parental weight, height, and socio demographics were recorded along with the child's weight and height measured at an ordinary child health care visit. We used the thresholds for children's BMI that were recommended for surveillance by the Royal College of Paediatrics and Child Health in 2012 based on the WHO reference population. RESULTS: Among the toddlers, 33 % had a BMI above the WHO 85(th) percentile and 14 % had a BMI above the WHO 95(th) percentile. The probability of a toddler having a BMI above the WHO 95(th) percentile was significantly increased if either the mother or father was overweight (BMI >= 25 kg/m(2)). Furthermore, we found a positive synergistic effect between the mother and father being overweight and their child having a BMI above the WHO 85(th) percentile. No associations were found between the toddlers' BMI and the family's socio-demographics, but there were associations between the parents' BMI and the family's socio-demographics. CONCLUSION: High BMI is common even in toddlers in this population. The risk increases if one parent is overweight, and it increases even more if both parents are overweight. The results in this study confirm the importance of considering familial risk factors when examining child health and BMI at ordinary child health care visits already at an early age. PMID- 26679344 TI - The transcriptional profile of coronary arteritis in Kawasaki disease. AB - BACKGROUND: Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment. METHODS: Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD. RESULTS: T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor alpha pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis. CONCLUSIONS: The immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high risk KD patients, and provide direction for future etiologic studies. PMID- 26679346 TI - Early surgery in Crohn's disease patients with entero-urinary fistulas: does it change the prognosis? AB - BACKGROUND: Entero-urinary fistulas (EUF) are observed in only 2-8% of Crohn's disease (CD) patients. AIM: To compare the outcome of patients with EUF, after surgical treatment, with those with non-penetrating and non-stenosing, penetrating, and stenosing phenotypes (B1, B2, and B3 phenotypes). METHODS: Case control study of 21 CD patients with EUF submitted to surgical treatment. Each patient with EUF was compared with six patients, two of each group: B1, B2, and B3 phenotypes. They were randomly selected from inflammatory bowel disease database and had the same extent of disease, smoking status, perianal disease, and age at diagnosis. RESULTS: One hundred and forty-seven patients were included (n = 21 EUF; n = 42 of each group B1, B2, and B3). Comparing B3 group with EUF, the former was more steroid-dependent and resistant (54.8% versus 19.0%, p = 0.037) and needed anti-TNF therapy more frequently (59.5% versus 23.8%, p = 0.004). Moreover, B3 patients had a poorer response to anti-TNF therapy without remission free of steroid therapy in comparison with EUF patients (45.2% versus 95.2%, p < 0.001). EUF patients did not differ from B2 group regarding anti-TNF therapy (p = 0.956) and steroid-dependence or resistance (p = 0.141). Surgery rate after index surgery was inferior in EUF in comparison with B2 and B3 groups. Hospital admission rate of patients with EUF was also lower than the B3 group. CONCLUSION: Early surgery seems to be a good choice for patients with EUF as their response to surgery appears not to differ from B2 patients and had a better prognosis than phenotype B3 patients. PMID- 26679347 TI - CloudForest: A Scalable and Efficient Random Forest Implementation for Biological Data. AB - Random Forest has become a standard data analysis tool in computational biology. However, extensions to existing implementations are often necessary to handle the complexity of biological datasets and their associated research questions. The growing size of these datasets requires high performance implementations. We describe CloudForest, a Random Forest package written in Go, which is particularly well suited for large, heterogeneous, genetic and biomedical datasets. CloudForest includes several extensions, such as dealing with unbalanced classes and missing values. Its flexible design enables users to easily implement additional extensions. CloudForest achieves fast running times by effective use of the CPU cache, optimizing for different classes of features and efficiently multi-threading. https://github.com/ilyalab/CloudForest. PMID- 26679348 TI - Patterns of Vertebrate Diversity and Protection in Brazil. AB - Most conservation decisions take place at national or finer spatial scales. Providing useful information at such decision-making scales is essential for guiding the practice of conservation. Brazil is one of the world's megadiverse countries, and consequently decisions about conservation in the country have a disproportionate impact on the survival of global biodiversity. For three groups of terrestrial vertebrates (birds, mammals, and amphibians), we examined geographic patterns of diversity and protection in Brazil, including that of endemic, small-ranged, and threatened species. To understand potential limitations of the data, we also explored how spatial bias in collection localities may influence the perceived patterns of diversity. The highest overall species richness is in the Amazon and Atlantic Forests, while the Atlantic Forest dominates in terms of country endemics and small-ranged species. Globally threatened species do not present a consistent pattern. Patterns for birds were similar to overall species richness, with higher concentrations of threatened species in the Atlantic Forest, while mammals show a more generalized pattern across the country and a high concentration in the Amazon. Few amphibians are listed as threatened, mostly in the Atlantic Forest. Data deficient mammals occur across the country, concentrating in the Amazon and southeast Atlantic Forest, and there are no data deficient birds in Brazil. In contrast, nearly a third of amphibians are data deficient, widespread across the country, but with a high concentration in the far southeast. Spatial biases in species locality data, however, possibly influence the perceived patterns of biodiversity. Regions with low sampling density need more biological studies, as do the many data deficient species. All biomes except the Amazon have less than 3% of their area under full protection. Reassuringly though, rates of protection do correlate with higher biodiversity, including higher levels of threatened and small-ranged species. Our results indicate a need for expanded formal protection in Brazil, especially in the Atlantic forest, and with an emphasis on fully protected areas. PMID- 26679349 TI - Nuclear Waste Facing the Test of Time: The Case of the French Deep Geological Repository Project. AB - The purpose of this article is to consider the socio-anthropological issues raised by the deep geological repository project for high-level, long-lived nuclear waste. It is based on fieldwork at a candidate site for a deep storage project in eastern France, where an underground laboratory has been studying the feasibility of the project since 1999. A project of this nature, based on the possibility of very long containment (hundreds of thousands of years, if not longer), involves a singular form of time. By linking project performance to geology's very long timescale, the project attempts "jump" in time, focusing on a far distant future, without understanding it in terms of generations. But these future generations remain measurements of time on the surface, where the issue of remembering or forgetting the repository comes to the fore. The nuclear waste geological storage project raises questions that neither politicians nor scientists, nor civil society, have ever confronted before. This project attempts to address a problem that exists on a very long timescale, which involves our responsibility toward generations in the far future. PMID- 26679350 TI - An ultra-radical surgical approach for recurrent vulvar cancer involving en-bloc excision of the infra-renal aorta. PMID- 26679351 TI - Jesus the Healer: A Sermon in Honor of the Memory of Donald Eric Capps (1939 2015). AB - The article below is a sermon preached in 2008. It was inspired by Donald Capps's book, Jesus the Village Psychiatrist. I offer this sermon in honor of his memory as a creative contributor to the work of the Journal as well as his distinguished career as Professor of Pastoral Theology at Princeton Theological Seminary. Many of us have been blessed by his profound psychological and theological insights into the human psyche, his scholarly explorations of the relationship of psychology and religion, and his remarkable sense of humor. We are diminished by his absence. PMID- 26679352 TI - Peptidoglycan Perception in Plants. PMID- 26679353 TI - Asymmetric light reflectance from metal nanoparticle arrays on dielectric surfaces. AB - Asymmetric light reflectance associated with localized surface plasmons excited in metal nanoparticles on a quartz substrate is observed and analyzed. This phenomenon is explained by the superposition of two waves, the wave reflected by the air/quartz interface and that reflected by the metal nanoparticles, and the resulting interference effects. Far field behavior investigation suggests that zero reflection can be achieved by optimizing the density of metal nanoparticles. Near field behavior investigation suggests that the coupling efficiency of localized surface plasmon can be additionally enhanced by separating the metal NPs from substrates using a thin film with refractive index smaller than the substrate. The latter behavior is confirmed via surface-enhanced Raman spectroscopy studies using metal nanoparticles on Si/SiO2 substrates. PMID- 26679354 TI - Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function. AB - Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in patients receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that zoledronate (ZOL), an anti-resorptive nitrogen containing bisphosphonate, significantly extended survival in patients affected by osteoporosis. The effect was too large to be simply due to the prevention of fractures. Moreover, in combination with statins, it extended the lifespan in a mouse model of Hutchinson Gilford Progeria Syndrome. Therefore, we asked whether ZOL was able to extend the lifespan of human MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of ZOL before irradiation protected the survival of mesenchymal progenitors in mice. Through mechanistic studies, we were able to show that inhibition of mTOR signaling, a pathway involved in longevity and cancer, was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in cancer patients and during ex vivo expansion for regenerative medicine approaches. Given that ZOL is already in clinical use with a good safety profile, these opportunities can be readily translated for patient benefit. PMID- 26679356 TI - Atopic disease and cardiovascular risk factors in US children. PMID- 26679357 TI - Current strategies for prevention of oral manifestations of human immunodeficiency virus. AB - OBJECTIVES: Strategies to prevent new-onset and recurrent oral manifestations of human immunodeficiency virus (HIV), including fungal, viral, neoplastic, and idiopathic mucosal diseases and destructive periodontal conditions, are poorly understood. STUDY DESIGN: A structured review of the English language literature in PubMed through March 2015 was conducted to identify current prevention strategies for initial and recurrent oral manifestations of HIV. RESULTS: Pharmacologic approaches, including combination antiretroviral therapy or other targeted therapies for prevention of oropharyngeal candidiasis, orolabial herpes, oral hairy leukoplakia, oral Kaposi sarcoma, linear gingival erythema and necrotizing ulcerative periodontitis were found. Nonpharmacologic approaches for prevention of oropharyngeal candidiasis, orolabial herpes, oral hairy leukoplakia, and necrotizing ulcerative periodontitis are presented. CONCLUSIONS: Current strategies for the prevention of oral manifestations of HIV include pharmacologic and nonpharmacologic therapies. Immune reconstitution inflammatory syndrome, future vaccine therapy for pathogens causing oral mucosal disease, and the possible role of oral inflammatory disease prevention in controlling HIV disease progression are discussed. PMID- 26679355 TI - Protein Footprinting by Carbenes on a Fast Photochemical Oxidation of Proteins (FPOP) Platform. AB - Protein footprinting combined with mass spectrometry provides a method to study protein structures and interactions. To improve further current protein footprinting methods, we adapted the fast photochemical oxidation of proteins (FPOP) platform to utilize carbenes as the footprinting reagent. A Nd-YAG laser provides 355 nm laser for carbene generation in situ from photoleucine as the carbene precursor in a flow system with calmodulin as the test protein. Reversed phase liquid chromatography coupled with mass spectrometry is appropriate to analyze the modifications produced in this footprinting. By comparing the modification extent of apo and holo calmodulin on the peptide level, we can resolve different structural domains of the protein. Carbene footprinting in a flow system is promising. PMID- 26679358 TI - Acrylic orthodontic retainer is not a risk factor for focal Candida colonization in young healthy patients: a pilot study. AB - BACKGROUND: Denture enhances the risk of Candida colonization because of adherence to acrylic base and interference with salivary rinsing. Acrylic orthodontic appliances may also create retentive areas for food debris and microbial pathogens; moreover, patients are instructed to use the retainers at night, when salivary secretion is reduced. We studied the Candida colonization in orthodontic patients using acrylic retainer. METHODS: Participants were orthodontic patients with full compliance during the retention phase with no signs or symptoms or being at risk for Candida, divided into users of (a) Hawley retainer (study group) and (b) other retainers (vacuum-formed/fixed bonded retainer; control group). Collected data included demographic characteristics and habits. Samples were collected from palate mucosa, cultured and incubated (28 degrees C) for 3 days. Positive Candida species were recultured to identify the Candida species. RESULTS: Fifty-one patients participated (mean age 20.9 +/- 9.6 years); 22 had maxillary Hawley retainer and 29 had maxillary vacuum-formed/fixed bonded retainer. Candida albicans colonization in the hard palate was identified in 2 patients (3.9%)-1 (4.5%) from the Hawley retainer study group and 1 (3.4%) from the control group. CONCLUSIONS: The hypothesis that palatal coverage by acrylic orthodontic retainer might enhance Candida colonization on the palatal mucosa is not supported by this pilot study. PMID- 26679359 TI - Dosimetric distribution to tooth-bearing areas in intensity-modulated radiation therapy for head and neck cancer: a pilot study. AB - OBJECTIVES: Dosimetric distribution of intensity-modulated radiotherapy (IMRT) to tooth-bearing areas for common head and neck (H&N) cancer sites were analyzed to facilitate minimization of osteoradionecrosis (ORN) risk through preradiation dental treatment planning. STUDY DESIGN: Fifty-four patients received IMRT with prescribed doses ranging from 6000 centigrays (cGy) (adjuvant) to 6930 cGy (primary) to treat base of tongue (BOT), tonsil, larynx, nasopharynx, and hypopharynx cancers. The average maximal radiation dose delivered was recorded in tooth-bearing areas (anteriors, premolars, and first, second, and third molars) of the maxilla and mandible. RESULTS: All tooth-bearing areas in laryngeal cancer cases received less than 2500 cGy. Maxillary and mandibular molar regions for BOT, tonsil, and hypopharynx cancers received 5000 cGy or higher. In nasopharynx cancers, maxillary teeth received higher doses than mandibular teeth. CONCLUSIONS: Among 5 H&N subsites, mandibular molar regions for BOT, tonsil, and hypopharynx cancers received higher IMRT doses on average, posing the greatest ORN risk. PMID- 26679360 TI - c-Jun, pc-Jun, and p27 are differently expressed in oral leukoplakias in smokers and never-smokers. AB - OBJECTIVE: Oral cancer may be preceded by potentially malignant lesions, and smoking is a risk factor. Oral leukoplakia (OL), which is the most common among these lesions, is defined by the World Health Organization as "a white plaque of questionable risk having excluded known diseases or disorders that carry no increased risk for cancer." Thus, OL is a clinical diagnosis used to designate oral white lesions, which are histologically represented by hyperkeratosis associated or not associated with epithelial dysplasia. It is known that c-Jun and pc-Jun have a role in cell proliferation and that p27 is decreased during carcinogenesis; thus, the aim of this study was to investigate whether these proteins are differently expressed in OL in smokers and never-smokers. STUDY DESIGN: Seventy-three cases diagnosed as OL were selected and divided into four groups according to the presence or absence of dysplasia and patients' smoking status (smokers: 39 cases, 24 dysplastic; never-smokers: 34 cases, 20 dysplastic). The immunoexpressions of c-Jun, pc-Jun, and p27 were evaluated. RESULTS: A significant correlation between smoking condition and the percentages of c-Jun (P = .0356) and pc-Jun (P = .0216) was found and was more intense in cases that underwent malignant transformation (6/47). CONCLUSIONS: Smoking habits may be linked to the expression of proteins directly associated with cell cycle progression. PMID- 26679361 TI - The presence of calcifications along the course of internal carotid artery in Greek and Brazilian populations: a comparative and retrospective cone beam CT data analysis. AB - OBJECTIVES: We aimed to retrospectively compare the prevalence of soft tissue calcifications (STCs) depicted incidentally along the extra- and intracranial course of the internal carotid artery (ICA) on cone beam computed tomography examinations in 2 different populations (Greeks and Brazilians). METHODS: The cohort consisted of examinations of 232 Greeks and 174 Brazilians, for a total of 406 patients. The scans were evaluated for the presence of STCs along the course of the ICA, with data analyzed in each ethnic group according to gender and age criteria. RESULTS: In total, 355 STCs were recorded; 78 (22.0% of all STCs) and 58 (16.3%) were extracranials, and 128 (36.1%) and 91 (25.6%) were intracranials for Greeks and Brazilians, respectively. The chi(2) test indicated no statistical differences between Greeks and Brazilians in the occurrence of STCs; however, their prevalence differed between genders in those populations. The presence of lesions, both extra- and intracranially, was found to increase with age (P < .05). The odds ratios were estimated at 2.23 (95% CI, 1.81-2.74) and 3.26 (95% CI, 2.56-4.16) for extracranial and intracranial lesions, respectively, with increasing age. CONCLUSIONS: We found an equal distribution for both extra- and intracranial STCs among Greeks and Brazilians. The prevalence of lesions differed between genders within both populations. Aging was found to be a risk factor for STCs, as the odds ratio increased significantly. PMID- 26679362 TI - A spatial association between odontomas and the gubernaculum tracts. AB - OBJECTIVES: The purpose of this study was to identify the spatial relationship and/or association between odontomas and the gubernaculum tract or the dental sac and the characteristic findings for radiographic diagnosis of odontomas. STUDY DESIGN: The visualizations of the odontomas and the gubernaculum tract were retrospectively analyzed using cone beam computed tomography or multidetector computed tomography. RESULTS: Most of odontomas were within the gubernaculum tract or dental sac of unerupted permanent teeth on computed tomography. In some odontomas, the gubernaculum tract existed as a well-defined low density tract extending from the top of odontomas on computed tomography. CONCLUSIONS: A close spatial relationship and/or association between odontomas and the gubernaculum tract or dental sac on computed tomography may be used as one of the criteria for radiographic diagnosis of odontomas. Development of odontomas may be associated with the gubernaculum tract or dental sac of unerupted permanent teeth. PMID- 26679364 TI - Reply to the letter to the editor. PMID- 26679363 TI - Cone beam computed tomography-based models versus multislice spiral computed tomography-based models for assessing condylar morphology. AB - OBJECTIVE: To quantitatively compare condylar morphology using cone beam computed tomography (CBCT) and multislice spiral computed tomography (MSCT) virtual three dimensional surface models. STUDY DESIGN: The sample consisted of secondary data analyses of CBCT and MSCT scans obtained for clinical purposes from 74 patients treated with condylar resection and prosthetic joint replacement. Three dimensional surface models of 146 condyles were constructed from each scan modality. Across-subject models were approximated and voxel-based registration was performed between homologous CBCT and MSCT images, making it possible to create average CBCT- and MSCT-based condylar models. SPHARM-PDM software provided matching points on each corresponding model. ShapeAnalysisMANCOVA software assessed statistically significant differences between observers and imaging modalities. One-sample t-tests evaluated the null hypothesis that the mean differences between each CBCT- and MSCT-based model were not clinically significant (<.5 mm). Tests were conducted at a significance level of P < .05. RESULTS: ShapeAnalysisMANCOVA showed no statistically significant difference between the average CBCT- and MSCT-based models (P > .68). During pairwise comparison, the mean difference observed was .406 mm (SD, .173). One sample t test showed that mean differences between each set of paired CBCT- and MSCT-based models were not clinically significant (P = .411). CONCLUSION: Three-dimensional surface models constructed from CBCT images are comparable to those derived from MSCT scans and may be considered reliable tools for assessing condylar morphology. PMID- 26679365 TI - Erythema multiforme major secondary to a cosmetic facial cream: first case report. AB - BACKGROUND: Oral erythema multiforme (EM) major is an acute immune-mediated disorder typically involving the oral mucosa, triggered by a hypersensitivity reaction to an antigen. CASE SUMMARY: A 59-year-old woman presented to an oral medicine clinic with a chief complaint of "mystery disease" of 1 year's duration. The condition was described as repeated episodes of severe, painful, asymmetric oral lesions that responded to systemic steroid therapy. A previous oral biopsy described fibrinoid necrosis, mixed inflammation, and granulation tissue. A regimen of descending-dose prednisone was administered, and 3 weeks later the tissues appeared to be partially healed. Direct immunofluorescence staining of a biopsied oral mucosal lesion was negative. To rule out a drug causation, the patient discontinued hydrochlorothiazide and escitalopram oxalate. However, on steroid tapering, episodic lesions recurred. The patient was placed on combination systemic prednisone and azathioprine. The oral lesions resolved again, but new episodes occurred immediately after tapering. The patient's daily facial cosmetics were evaluated, and she was asked to stop using cosmetics with the active ingredient octocrylene. After eliminating the use of facial cosmetics containing octocrylene, the episodes no longer recurred. CONCLUSIONS: We report a case of cosmetic-induced EM major and suggest that the triggering allergen is octocrylene. PMID- 26679366 TI - Pseudoxanthoma elasticum of the palate: a case report and a brief review of the literature. AB - Pseudoxanthoma elasticum (PXE), which is a genetic, multi-target disorder characterized by progressive calcification and fragmentation of elastic fibers, affects several organs, including the eyes, skin, and cardiovascular system. Diagnosis of PXE is currently based on cutaneous and ocular signs, histopathologic findings, and a patient's family history. PXE-related oral mucosal lesions are rarely reported, possibly due to the potential for misdiagnosis as Fordyce spots; however, when such lesions are reported, they are primarily localized to the vestibular mucosa of the lower lip. Here, we report the case of a female with an intraoral presentation of PXE at the labial and palatal sites. PXE was previously suspected in this patient because of the presence of cardiovascular, ocular, and cutaneous signs; however, a cutaneous biopsy showed findings not consistent with PXE. Incisional biopsy of the palatal lesion confirmed the PXE diagnosis, leading to proper management of the disorder to prevent ophthalmologic and cardiovascular complications. PMID- 26679367 TI - Nucleos(t)ide analogs reduce the risk of hepatitis B-associated hepatocellular carcinoma: A can't miss proposition? PMID- 26679368 TI - Direct Write Protein Patterns for Multiplexed Cytokine Detection from Live Cells Using Electron Beam Lithography. AB - Simultaneous detection of multiple biomarkers, such as extracellular signaling molecules, is a critical aspect in disease profiling and diagnostics. Precise positioning of antibodies on surfaces, especially at the micro- and nanoscale, is important for the improvement of assays, biosensors, and diagnostics on the molecular level, and therefore, the pursuit of device miniaturization for parallel, fast, low-volume assays is a continuing challenge. Here, we describe a multiplexed cytokine immunoassay utilizing electron beam lithography and a trehalose glycopolymer as a resist for the direct writing of antibodies on silicon substrates, allowing for micro- and nanoscale precision of protein immobilization. Specifically, anti-interleukin 6 (IL-6) and antitumor necrosis factor alpha (TNFalpha) antibodies were directly patterned. Retention of the specific binding properties of the patterned antibodies was shown by the capture of secreted cytokines from stimulated RAW 264.7 macrophages. A sandwich immunoassay was employed using gold nanoparticles and enhancement with silver for the detection and visualization of bound cytokines to the patterns by localized surface plasmon resonance detected with dark-field microscopy. Multiplexing with both IL-6 and TNFalpha on a single chip was also successfully demonstrated with high specificity and in relevant cell culture conditions and at different times after cell stimulation. The direct fabrication of capture antibody patterns for cytokine detection described here could be useful for biosensing applications. PMID- 26679369 TI - Investigation of the dynamic bending properties of MoS2 thin films by interference colours. AB - A non-contact method for the observation of the elastic deformation of 2D molybdenum disulfide (MoS2) thin films using an ordinary optical microscope is reported. A pulsed laser is used to rapidly increase the bending deformation of the MoS2 thin films via heating. The bending angle of the MoS2 thin films shows high stability, changing only 5% in forty days without external forces. However, the bending angle of the MoS2 thin films substantially decreases after being wetted with the volatile polar solvent tetrahydrofuran (THF), because of its low surface tension. By removing the nano-Newton scale forces on the MoS2 thin films, the bending angle increases significantly within 4 minutes, and this feature of the thin films shows great potential for use in the fabrication of micro-force sensors. This is the first attempt to study the mechanical properties of 2D materials by optical methods. Further utilization of industrially manufactured MoS2 thin films for detecting micro-force qualitatively on the basis of their excellent bending properties would significantly reduce the production costs of micro-force sensors. PMID- 26679370 TI - The colour of an avifauna: A quantitative analysis of the colour of Australian birds. AB - Animal coloration is a poorly-understood aspect of phenotypic variability. Here I expand initial studies of the colour gamut of birds by providing the first quantitative description of the colour variation of an entire avifauna: Australian landbirds (555 species). The colour of Australian birds occupies a small fraction (19%) of the entire possible colour space and colour variation is extremely uneven. Most colours are unsaturated, concentrated in the centre of colour space and based on the deposition of melanins. Other mechanisms of colour production are less common but account for larger portions of colour space and for most saturated colours. Male colours occupy 45-25% more colour space than female colours, indicating that sexual dichromatism translates into a broader range of male colours. Male-exclusive colours are often saturated, at the edge of chromatic space, and have most likely evolved for signalling. While most clades of birds occupy expected or lower-than-expected colour volumes, parrots and cockatoos (Order Psittaciformes) occupy a much larger volume than expected. This uneven distribution of colour variation across mechanisms of colour production, sexes and clades is probably shared by avifaunas in other parts of the world, but this remains to be tested with comparable data. PMID- 26679371 TI - Conversion of a non-heme iron-dependent sulfoxide synthase into a thiol dioxygenase by a single point mutation. AB - EgtB from Mycobacterium thermoresistibile catalyzes O2-dependent sulfur-carbon bond formation between the side chains of Nalpha-trimethyl histidine and gamma glutamyl cysteine as a central step in ergothioneine biosynthesis. A single point mutation converts this enzyme into a gamma-glutamyl cysteine dioxygenase with an efficiency that rivals naturally evolved thiol dioxygenases. PMID- 26679373 TI - Base-Induced Liquid Crystals of Graphene Oxide for Preparing Elastic Graphene Foams with Long-Range Ordered Microstructures. AB - Base-induced graphene oxide (GO) liquid crystals form a highly ordered texture. This microstructure can be inherited by graphene foams prepared by hydrothermal reduction, showing a long-range ordered microstructure of graphene sheets in 3D. This provides an insightful understanding into the supramolecular chemistry of GO sheets. PMID- 26679374 TI - Efficacy comparison between minimally invasive and conventional surgery for lumbar disc herniation in Chinese Han population: a meta-analysis. AB - This corrects the article DOI: 10.1038/sc.2014.98. PMID- 26679372 TI - Abasic pivot substitution harnesses target specificity of RNA interference. AB - Gene silencing via RNA interference inadvertently represses hundreds of off target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ~ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID- 26679375 TI - Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre. AB - BACKGROUND: In contrast to the consistent evidence for obesity and colorectal cancer (CRC) risk, the impact of obesity in CRC patients is less clear. In a well characterised cohort of CRC patients, we prospectively evaluated class I and class II obesity with survival outcomes. METHODS: The CRC patients (N=634) were followed from the date of diagnosis until disease progression/first recurrence (progression-free survival (PFS)) or death (overall survival (OS)). Body mass index (BMI) was calculated from reported usual weight prior to diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic, treatment, and lifestyle factors. RESULTS: Over a median follow-up of 4 years, 208 (33%) patients died and 235 (37%) recurred or progressed. Class II obesity, as compared with either overweight or normal weight, was associated with an increased risk of death (HR and 95% CI: 1.55 (0.97 2.48) and 1.65 (1.02-2.68), respectively), but no clear association was observed with PFS. In analyses restricted to patients who presented as stages I-III, who reported stable weight, or who were aged <50 years, obesity was associated with a significant two- to five-fold increased risk of death. CONCLUSIONS: In CRC patients evaluated at a large cancer centre, severely obese patients experienced worse survival outcomes independent of many other factors. PMID- 26679377 TI - An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer. AB - BACKGROUND: Despite the importance of inflammation in cancer, the role of the cytokine IL-33, and its receptor ST2, in colon cancer is unclear. The aim of this study was to investigate the role of IL-33, and its receptor isoforms (ST2 and ST2L), in colon cancer. METHODS: Serum levels of IL-33 and sST2 were determined with ELISA. ST2 and IL-33 expression was detected with quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. ST2 expression in CT26 cells was stably suppressed using ST2-specific shRNA. Cytokine and chemokine gene expression was detected with qRT-PCR. RESULTS: Human colon tumours showed lower expression of ST2L as compared with adjacent non-tumour tissue (P<0.01). Moreover, the higher the tumour grade, the lower the expression of ST2L (P=0.026). Colon cancer cells expressed ST2 and IL-33 in vitro. Functional analyses showed that stimulation of tumour cells with IL-33 induced the expression of chemokine (C-C motif) ligand 2 (CCL2). Knockdown of ST2 in murine colon cancer cells resulted in enhanced tumour growth (P<0.05) in BALB/c mice in vivo. This was associated with a decrease in macrophage infiltration, with IL-33 induced macrophage recruitment reduced by antagonising CCL2 in vitro. CONCLUSION: The IL-33/ST2 signalling axis may have a protective role in colon carcinogenesis. PMID- 26679376 TI - Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers. AB - BACKGROUND: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. METHODS: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))- and EGFR-) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case-case comparison was performed using unconditional logistic regression. RESULTS: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. CONCLUSIONS: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non significant but suggestive differences in tumour features and family history warrant further investigations. PMID- 26679378 TI - Prediction of vascular invasion in hepatocellular carcinoma by next-generation des-r-carboxy prothrombin. AB - BACKGROUND: In hepatocellular carcinoma (HCC), des-r-carboxy prothrombin (DCP) more accurately reflects the malignant potential than alpha-fetoprotein (AFP). Next-generation DCP (NX-DCP) was created to overcome some of the limitations of conventional DCP. This study assessed the predictive value of NX-DCP for vascular invasion in HCC. METHODS: We prospectively studied 82 consecutive patients who were scheduled to undergo resection for HCC. Patients were divided into two groups according to the presence or absence of pathological vascular invasion. The predictive powers of AFP, conventional DCP, and NX-DCP for vascular invasion were compared by receiver operating characteristic curve analysis, and correlations with tumour markers and the presence of vascular invasion were assessed. RESULTS: Vascular invasion was pathologically confirmed in 21 patients (positive group) and absent in 61 patients (negative group). The NX-DCP level was significantly higher in the positive group than in the negative group (510.0 mAU ml(-1) (10-98 450) vs 34.0 mAU ml(-1) (12-541), P<0.0001), while the AFP level did not differ significantly between the groups (9.7 ng ml(-1) (1.6-43 960.0) vs 11.0 ng ml(-1) (1.6-1650.0), P=0.49). The area under the curve (AUC) of NX-DCP (AUC=0.813, sensitivity=71.4%, 1-specificity=13.1%) had good sensitivity for the prediction of vascular invasion, while the AUC of AFP was 0.550 (sensitivity=28.6%, 1-specificity=1.60%). The suitable cutoff value for identifying pathological vascular invasion in HCC was 33 mm (AUC: 0.783, sensitivity=71.43%, 1-specificity=11.48%). CONCLUSIONS: The NX-DCP level can be used to predict the presence of vascular invasion in HCC. PMID- 26679379 TI - Constructing a molecular interaction network for thyroid cancer via large-scale text mining of gene and pathway events. AB - BACKGROUND: Biomedical studies need assistance from automated tools and easily accessible data to address the problem of the rapidly accumulating literature. Text-mining tools and curated databases have been developed to address such needs and they can be applied to improve the understanding of molecular pathogenesis of complex diseases like thyroid cancer. RESULTS: We have developed a system, PWTEES, which extracts pathway interactions from the literature utilizing an existing event extraction tool (TEES) and pathway named entity recognition (PathNER). We then applied the system on a thyroid cancer corpus and systematically extracted molecular interactions involving either genes or pathways. With the extracted information, we constructed a molecular interaction network taking genes and pathways as nodes. Using curated pathway information and network topological analyses, we highlight key genes and pathways involved in thyroid carcinogenesis. CONCLUSIONS: Mining events involving genes and pathways from the literature and integrating curated pathway knowledge can help improve the understanding of molecular interactions of complex diseases. The system developed for this study can be applied in studies other than thyroid cancer. The source code is freely available online at https://github.com/chengkun-wu/PWTEES. PMID- 26679380 TI - EARLY ASSESSMENT AND PREDICTION OF POTENTIAL IMPACT OF THE IMPLANTATION OF POLYURETHANE SCAFFOLD IN PARTIAL MENISCAL LESIONS: A PILOT HORIZON SCANNING ACTIVITY IN SOUTH KOREA. AB - OBJECTIVES: The aim of this study was to predict the potential impact of the introduction of implantation of polyurethane scaffold for the treatment of partial meniscal lesions in the South Korean healthcare system. METHODS: The horizon scanning process was used to select a target technology and assess its potential impacts on patients and the Korean healthcare system. We identified and filtered research-phase health technologies that are not listed yet in Korean, but appear promising. After a process of prioritization, we chose the implantation of polyurethane scaffolds as a target technology. Then, through the procedures of assessment and peer review, we analyzed current evidence and its predicted potential impacts. RESULTS: There were eight studies included in the review: one prospective cohort and seven case-series studies. Six revealed significant improvements in function and pain relief. Of the six studies, which reported safety endpoints, four stated no major postoperative complications related to scaffold, and two reported adverse events and serious adverse events such as pain, joint swelling, et cetera. We also included the potential impact of this technology based on the experts' consultation. They all agreed that it would satisfy the diverse needs of patients and fulfill clinical needs. However, the majority of related clinical studies were based on short-term follow-up observations without any validation process involving comparison with control groups. CONCLUSIONS: Through a horizon scanning activity, we found that the implantation of polyurethane scaffolds is a promising technology to resolve articular cartilage defects; however, long-term evidence with comparison groups for safety and effectiveness is required. PMID- 26679381 TI - BMP-2 delivered via sucrose acetate isobutyrate (SAIB) improves bone repair in a rat open fracture model. AB - Human bone morphogenetic proteins (BMPs) are an alternative to bone graft for the treatment of high-energy open fractures. The standard delivery system for BMP-2 is a porous collagen sponge, but we have previously found that the biocompatible, high viscosity carrier, Sucrose acetate isobutyrate (SAIB) is an effective and potentially less invasive alternative. The efficacy of SAIB as a BMP-2 delivery system was examined in an open fracture model featuring a femoral osteotomy with periosteal stripping in 9-week-old male Sprague Dawley rats. SAIB containing BMP 2 (SAIB/BMP-2) was delivered into the fracture site during surgery and an additional group was further co-treated with zoledronic acid and hydroxyapatite nanoparticles (SAIB/BMP-2/HA/ZA). These were compared to untreated fractures and SAIB carrier alone (negative controls), and BMP-2 loaded collagen sponge (positive control). The rate of radiographic union and the biomechanical properties of the healed fractures were compared after 6-week. Untreated and SAIB treated fractures showed poor repair, with 53% and 64%, respectively, not bridged at 6 week. In contrast, collagen/BMP-2, SAIB/BMP-2, and SAIB/BMP-2/HA/ZA showed significantly increased union (100%, 100%, and 94%, respectively, p < 0.05). Four point bend testing revealed that collagen/BMP-2 and SAIB/BMP-2/HA/ZA restored the strength of fractured femora to that of intact femora by 6 week, whereas untreated and SAIB remained less than intact controls by 60% and 67%, respectively (p < 0.05). Overall, the SAIB/BMP-2/HA/ZA formulation was comparable to BMP-2 infused collagen sponge in terms of promoting open fractures repair, but with the additional potential for less invasive delivery. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1168-1176, 2016. PMID- 26679382 TI - Iodine(III)-Mediated Oxidative Hydrolysis of Haloalkenes: Access to alpha-Halo Ketones by a Release-and-Catch Mechanism. AB - An unprecedented iodine(III)-mediated oxidative transposition of vinyl halides has been accomplished. The products obtained, alpha-halo ketones, are useful and polyvalent synthetic precursors. There are only a handful of reported examples of the direct conversion of vinyl halides to their corresponding alpha-halo carbonyl compounds. Insights into the mechanism and demonstration that this synthetic transformation can be done under enantioselective conditions are reported. PMID- 26679383 TI - Taiwanese Dermatological Association consensus for the definition, classification, diagnosis, and management of urticaria. AB - BACKGROUND/PURPOSE: This report describes the 2014 consensus of the Taiwanese Dermatological Association regarding the definition, classification, diagnosis, and management of urticaria. This consensus is distributed to practices throughout Taiwan to provide recommendations for diagnostic and therapeutic approaches for common subtypes of urticaria, in order to improve the quality of life of urticaria patients. The consensus, thus, serves as an important reference for dermatologists throughout Taiwan. METHODS: All the consensus contents were voted on by the participating dermatologists, with approval by no less than 75% being required for inclusion. The consensus provides a comprehensive overview of urticaria, including recent advances in identifying its causes and the processes by which it develops. RESULTS: All the consensus meeting attendees agreed to a definition of urticaria, which states that it is characterized by the sudden appearance of wheals (also known as hives), angioedema, or both. Most of the experts (16 out of 19, or 84.2%) agreed that chronic urticaria is defined as the sudden occurrence of wheals and/or angioedema for a period of >= 6 weeks. In addition, the consensus attendees also approved the Urticaria Activity Score system or the Urticaria Activity Score for 7 days system as the recommended method for assessing disease activity in spontaneous urticaria. CONCLUSION: It was also determined that the treatment goal for patients with any form of urticaria should be complete cessation of suffering from all urticaria symptoms. The recommended treatment algorithms for chronic spontaneous urticaria and acute urticaria were finally proposed and approved by 100% (19/19) and 84.2% (16/19) of the consensus attendees, respectively. PMID- 26679384 TI - Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes. AB - Contrave((r)) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. Its safety and efficacy were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects: COR-1, COR-II, COR-BMOD and COR-DM. All four studies demonstrated statistically significant and clinically meaningful weight loss following up to 52 weeks of treatment with naltrexone/bupropion compared with placebo. The average weight loss from baseline across the four studies was approximately 11-22 lbs (5-9 kg). Results show the efficacy of Contrave for weight loss, as well as significant improvements in cardiometabolic markers. This review focuses on the four studies, their outcomes and the mechanism of action of Contrave. PMID- 26679385 TI - Spontaneous retinal pigment epithelium tear in geographic atrophy. AB - PURPOSE: To report two cases of spontaneous retinal pigment epithelial (RPE) tears occurring in two patients affected with geographic atrophy (GA) due to non exudative age-related macular degeneration (AMD). CASE REPORT: Two patients (a 79 year-old man and a 71-year-old woman) presented to our department with progressive visual loss. The man had a best-corrected visual acuity (BCVA) of 20/100 in the right eye (RE) and 20/50 in the left eye (LE); the woman had a BCVA of 20/200 in the RE and 20/160 in the LE. Upon complete ophthalmologic examination, revealing a large area of atrophy (>175 MUm in diameter) along with pigmentary changes, calcified drusen and no choroidal neovascularization (CNV) in either eye, the patients were diagnosed with GA due to non-exudative AMD. Interestingly, the imaging modalities performed, including fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT), clearly highlighted the presence of spontaneous RPE tears in the context of non-exudative AMD, while in general, RPE tears are a well-recognized complication of exudative AMD. CONCLUSIONS: To our knowledge, this is the first description of spontaneous RPE tears as a possible complication of GA due to non-exudative AMD. PMID- 26679386 TI - Beyond-the-edge proliferation after relaxing retinectomy. AB - PURPOSE: To report beyond-the-edge proliferation (BTEP) after relaxing retinectomies (RR) i.e. fibrous sheets stretched between the RR edge and the far periphery; to evaluate the tractional potential and report the long-term course of BTEP. METHODS: Retrospective review of the medical records of 83 patients having undergone a RR between January 2009 and December 2014 to identify patients with BTEP. RESULTS: Six patients aged 31 to 76 were identified. Retinectomy had been performed for traumatic retinal incarceration in one case and anterior PVR in 5 cases. BTEP occurred within weeks of the RR (earliest: 5 weeks). It was discovered intraoperatively in two patients with silicone oil tamponade, at 7 weeks and 6 months respectively after RR. It recurred over a few months after excision in 5 patients, causing inferior tractional retinoschisis in 4 patients and inferior tractional retinal detachment in two patients. CONCLUSIONS: BTEP is an unusual form of proliferative vitreoretinopathy developing despite the absence of the usual vitreo-retinal support (excised during RR), probably through compartmentalization and cell migration along the inferior interface between silicone oil or gas and the aqueous humour. BTEP can cause serious retinal traction, develops over weeks after the RR and recurs frequently a few months after excision. PMID- 26679387 TI - [Neurotrophic keratitis after vitrectomy and circumferential endophotocoagulation for retinal detachment]. AB - INTRODUCTION: Circumferential (360 degrees ) endophotocoagulation is frequently implemented during vitrectomies for retinal detachment. This photocoagulation may result in neurotrophic keratitis by damaging the ciliary nerves in the suprachoroidal space on their way to the pupil. We report a series of 4 cases of neurotrophic keratitis following a circumferential endophotocoagulation. PATIENTS AND METHODS: A retrospective observational case series of 4 non-diabetic patients having presented with a neurotrophic keratitis following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation (532 nm) at Caen University Hospital. We report the various forms of corneal lesions and the diagnostic criteria allowing for the diagnosis of neurotrophic keratitis. DISCUSSION: Neurotrophic keratitis is caused by lesions occurring at various levels of corneal innervation. Endophotocoagulation may cause a neurotrophic keratitis by damaging the short and long ciliary nerves on their way to the pupil in the suprachoroidal space. The sequelae of this condition can limit visual recovery. Hence, it is probably advisable to screen for corneal anesthesia or severe hypesthesia following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation and to implement prophylactic treatment (intensive lubricant therapy; preservative-free eye drops) if needed. CONCLUSION: The risk of neurotrophic keratitis should be weighed against the dose of laser retinopexy necessary and sufficient to obtain a sustained retinal reattachment. If circumferential endophotocoagulation is implemented, it is probably sensible to monitor corneal sensitivity and to adapt postoperative treatment if necessary. PMID- 26679388 TI - The contribution of sensory nerves to the onset threshold for cutaneous vasodilatation during gradual local skin heating of the forearm and leg. AB - During local skin heating, the temporal onset of vasodilatation is delayed in the leg compared to the forearm, and sensory nerve blockade abolishes these differences. However, previous work using rapid skin heating did not allow for determination of sensory nerve influences on temperature thresholds for vasodilatation. Two sites were examined on both the forearm and leg, one control (CTRL), and one treated for sensory nerve blockade (EMLA). Skin blood flux was monitored using laser-Doppler probes, with heaters controlling local skin temperature (Tloc). Tloc was increased from 32-44 degrees C (+1 degrees C.10 min(-1)). Stimulus-response curves were constructed by fitting a four-parameter logistic function. EMLA significantly increased Tloc onset in the forearm (CTRL=35.3 +/- 0.4 degrees C; EMLA=36.8 +/- 0.7 degrees C) and leg (CTRL=36.5 +/- 0.4 degrees C; EMLA=38.4 +/- 0.5 degrees C; both P<0.05). At both CTRL and EMLA, Tloc onset was higher in the leg compared to the forearm (both P<0.05). In the forearm, median effective temperature to elicit 50% vasodilatation (ET50) was similar between sites (CTRL=39.7 +/- 0.3 degrees C; EMLA=40.2 +/- 0.4 degrees C; P=0.09); however, in the leg, EMLA significantly increased ET50 (CTRL=40.2 +/- 0.3 degrees C; EMLA=41.0 +/- 0.3 degrees C)(P<0.05). At CTRL sites, no limb difference was observed for ET50 (P=0.06); however, with EMLA, ET50 was significantly higher in the leg (P<0.05). EMLA significantly increased the gain of the slope at the forearm, (CTRL=0.31 +/- 0.01%CVCmax. degrees C(-1); EMLA=0.45 +/- 0.07%CVCmax. degrees C(-1)), and leg (CTRL=0.37 +/- 0.05%CVCmax. degrees C( 1); EMLA=0.54 +/- 0.04%CVCmax. degrees C(-1))(both P<0.05). At CTRL sites, the gain was significantly higher in the leg (P<0.05); however, for EMLA, no significant limb difference existed (P=0.10). These data indicate that the onset of vasodilatation occurs at a lower temperature in the forearm than the legs, and sensory nerves play an important role in both limbs. PMID- 26679390 TI - Psychosomatic breast and alexithymic breast: A Bionian psychosomatic perspective. AB - The author develops the concept of 'psychosomatic breast' in both clinical and theoretical terms, a concept developed by Bion (1962b) to account for a breast in charge of primary symbolization and of the psychosomatic integration of the infant's raw physiological, emotional and sensory experiences. As such, the psychosomatic breast is a prototype, a core in the mother endowed with the capacity for reverie insofar as the transformative function of the latter not only pertains to the primary symbolization of emotional life, but also to its secondary symbolization. The author contends that a primal failure in the transformation of such raw emotional and sensory experiences through the reverie of primary objects results in the incorporation of an 'alexithymic breast' - a kind of obstructive object that has become impervious to communication via projective identification and has been internalized as a source of psychic and physical breakdown. This early deficiency in parental reverie is experienced by the infant as a primitive disaster that establishes a point of fixation, a fault line in psychosomatic organization which the individual is likely to regress to, at a later stage, by developing physical illness. The author illustrates the dynamics and the economy of the conflict between psychosomatic and alexithymic breasts thanks to fragments from the analysis of a woman who developed cancer in the course of her psychoanalysis and was eventually cured. PMID- 26679391 TI - Foreword. PMID- 26679389 TI - Protective effects of monomethyl fumarate at the inflamed blood-brain barrier. AB - BACKGROUND: Reactive oxygen species play a key role in the pathogenesis of multiple sclerosis as they induce blood-brain barrier disruption and enhance transendothelial leukocyte migration. Thus, therapeutic compounds with antioxidant and anti-inflammatory potential could have clinical value in multiple sclerosis. The aim of the current study was to elucidate the therapeutic effects of monomethyl fumarate on inflammatory-mediated changes in blood-brain barrier function and gain insight into the underlying mechanism. METHODS: The effects of monomethyl fumarate on monocyte transendothelial migration across and adhesion to inflamed human brain endothelial cells (hCMEC/D3) were quantified using standardized in vitro migration and adhesion assays. Flow cytometry analysis and qPCR were used to measure the concomitant effects of monomethyl fumarate treatment on protein expression of cell adhesion molecules. Furthermore, the effects of monomethyl fumarate on the expression and nuclear localization of proteins involved in the activation of antioxidant and inflammatory pathways in human brain endothelial cells were elucidated using nuclear fractionation and Western blotting. Statistical analysis was performed using one-way ANOVA followed by the Bonferroni post-hoc test. RESULTS: Our results show that monomethyl fumarate induced nuclear translocation of nuclear factor (erythroid-derived 2) like 2 and concomitant production of the antioxidant enzymes heme oxygenase-1 and NADPH:quinone oxidoreductase-1 in brain endothelial cells. Importantly, monomethyl fumarate treatment markedly decreased monocyte transendothelial migration across and adhesion to inflamed human brain endothelial cells. Treatment of brain endothelial cells with monomethyl fumarate resulted in a striking reduction of vascular cell adhesion molecule expression. Surprisingly, monomethyl fumarate did not affect nuclear translocation of nuclear factor-kB suggesting that monomethyl fumarate potentially affects activity of nuclear factor-KB downstream of nuclear translocation. CONCLUSIONS: Taken together, we show that monomethyl fumarate, the primary metabolite of dimethyl fumarate, which is currently used in the clinics for the treatment of relapsing-remitting multiple sclerosis, demonstrates beneficial therapeutic effects at the inflamed blood-brain barrier. PMID- 26679392 TI - Improving care and treatment options for women and girls with bleeding disorders. AB - Women and girls may experience increased bleeding symptoms as carriers of haemophilia. They can also be affected by other hereditary bleeding diatheses such as von Willebrand disease, platelet dysfunction defects or deficiencies of coagulation factors (F) such as FI, FII, FV, FVII, FX, FXI and FXIII. In addition to general bleeding symptoms, such disorders pose unique problems for women due to their impact on reproductive health. Women and adolescent girls with undiagnosed bleeding disorders frequently experience heavy menstrual bleeding (HMB; menorrhagia), leading to impairment of daily activities. Other gynaecological and obstetric manifestations, for example miscarriage, bleeding during pregnancy and postpartum haemorrhage (PPH), can occur. Treatment for HMB should consider patient wishes relating to preservation of fertility, and management options include hormonal measures, desmopressin, antifibrinolytics, platelet concentrate transfusions and clotting factor therapy. During pregnancy, monitoring clotting factor levels informs the need for prophylactic therapy; subsequent haemostatic cover can minimise PPH. Under-recognition of bleeding disorders in females may lead to inappropriate, or lack of, treatment. This may be avoided by increased disease awareness, prompt and accurate diagnosis, and a multidisciplinary approach to patient care. This review considers the range of hereditary bleeding disorders that may affect women and adolescent girls, and their evaluation and management. PMID- 26679393 TI - Optimising musculoskeletal care for patients with haemophilia. AB - Despite recent improvements in the quality of care and treatment outcomes for haemophilia, joint disease remains a major concern for patients with and without inhibitors. Most bleeding episodes occur in the musculoskeletal system, and recurrent bleeding may result in progressive joint damage, leading to haemophilic arthropathy. Consequently, early identification and management of musculoskeletal bleeding episodes are important to prevent crippling deformities and dysfunction. Management strategies should aim at optimising joint function by reducing the frequency of, and preventing, joint bleeds. Although prophylactic factor replacement is proven to be effective in reducing bleeding frequency into joints and preserving musculoskeletal function in patients without inhibitors, the role for prophylaxis (with bypassing agents) in patients with inhibitors remains unclear. The available bypassing agents, activated prothrombin complex concentrate and recombinant activated factor VII (rFVIIa), are currently the standard of care for acute bleeding episodes in patients with high-titre inhibitors. These agents also prevent bleeding during elective orthopaedic surgery (EOS) in this patient population. This review discusses published data and uses illustrative cases to describe effective strategies for assessing joint health and maintaining optimal musculoskeletal care, focusing on the use of rFVIIa for haemostatic control in haemarthroses and when EOS is required in patients with inhibitors. PMID- 26679394 TI - Updates from guardianTM: a comprehensive registration programme. AB - Turoctocog alfa is an approved B-domain truncated recombinant factor VIII concentrate for adults and children with haemophilia A. Clinical data for turoctocog alfa have been reported from the guardian(TM) 1, guardian(TM) 2 and guardian(TM) 3 phase III trials. guardian(TM) 1 and guardian(TM) 3 phase III trials enrolled 150 adolescents/adults (>= 12 yr), and 63 children (<12 yr), respectively, with previously treated severe haemophilia A and no history of inhibitors; 188 of these patients continued into the ongoing guardian(TM) 2 extension trial. In the three trials, patients have received prophylaxis with turoctocog alfa three times weekly or every second day, with breakthrough bleeds resolved to an expected postinjection level of >= 0.50 IU/mL. No safety concerns have arisen, and no patients have developed confirmed inhibitors (primary endpoint). Indeed, no confirmed inhibitors have been detected in >200 patients treated for a cumulative total of >54,000 exposure days in the phase III trials. Pooled efficacy data show a favourable long-term effect of turoctocog alfa on annualised bleeding rate and a success rate for haemostatic response of 86%; 90% of bleeds were resolved with 1-2 doses. This article reviews the clinical development of turoctocog alfa with reference to the guardian(TM) clinical programme, describing results obtained to date and ongoing trials. PMID- 26679395 TI - Challenges in the management of haemophilia on transition from adolescence to adulthood. AB - Patients with haemophilia undergo many transitions during their lives, but the period between adolescence and adulthood is particularly challenging. During this time, the patient must deal with all of the typical biological, social and emotional changes associated with this phase of life, whilst at the same time, adapting his lifestyle to the needs of his condition, transferring from paediatric to adult services and, most importantly, accepting increasing (and ultimately full) responsibility for managing his condition. Parents may also find their diminishing role equally challenging. Perhaps not surprisingly, given the challenges that adolescents face, treatment adherence during this time is generally low, which can lead to recurrent joint bleeds, chronic pain and reduced quality of life. To address the challenges, it is critical that a transition programme is put in place that meets the needs of not only the patient, but also his parents and healthcare providers. Key elements of the plan are a multidisciplinary approach, early planning, patient education and appropriate follow-up. A successful programme will equip all parties with the skills to deal with the challenges of transition from adolescence to adulthood, ensuring that the benefits of treatment in childhood are maintained, thus optimising health outcomes and quality of life. PMID- 26679396 TI - Acquired haemophilia: an overview for clinical practice. AB - Acquired haemophilia is a potentially life-threatening bleeding disorder caused by the development of autoantibodies against coagulation factors, most commonly against factor (F) VIII (acquired haemophilia A; AHA). In around half of patients, an underlying disorder is associated with AHA; the remaining cases are idiopathic. Typically, the disorder presents with bleeding, ranging from mild to life- and limb-threatening, in patients with no personal or family bleeding history. Diagnosis involves an isolated prolongation of the activated partial thromboplastin time, without correction in mixing studies, low FVIII activity levels and evidence of a FVIII inhibitor. As AHA is rare, a lack of familiarity of the condition may result in delayed diagnosis, and prompt haemostatic control is required to reduce morbidity and mortality. Bypassing agents (recombinant activated factor VII or activated prothrombin complex concentrates) can be used to control acute bleeding, and immunosuppression is necessary to eradicate the inhibitor. As clinical trials in this rare and heterogeneous disease are difficult, current evidence comes from observational studies, including registries. This review will focus on the diagnostic and therapeutic challenges of AHA and summarise how understanding of this complex condition has increased based on recent registry data. PMID- 26679399 TI - Intensive training but no benefits to everyday life: computerised cognitive training. PMID- 26679398 TI - Is the pattern of dietary amino acids intake associated with serum lipid profile and blood pressure among individuals with spinal cord injury? AB - OBJECTIVE: The probable effect of dietary amino acids intake pattern on serum lipid profile and blood pressure (BP) have not yet been described among individuals with spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: Tertiary rehabilitation center. PARTICIPANTS: People with SCI referred to Brain and Spinal Cord Injury Research Center between 2011 and 2014. OUTCOME MEASURES: Dietary intakes were assessed by recording consumed foods by 24-hour dietary recall interviews using Nutritionist IV 3.5.3 modified for Iranian foods. Partial correlation test with adjustment for age, weight, body mass index, total energy intake, total fat, cholesterol and carbohydrate intake, and injury-related variables was used. RESULTS: Dietary intake of lysine was positively related to levels of fasting plasma glucose (FPG), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.0001, 0.046, 0.002 and 0.009, respectively). There was a positive significant relationship between the intake of cysteine and levels of TG and SBP as well (P : 0.027 and 0.048, respectively). Higher intakes of threonine and leucine had a negative relationship with TG level (P : 0.001 and 0.026, respectively). Furthermore, tyrosine, threonine and leucine were inversely correlated to blood pressure. Total cholesterol level was only related to intake of threonine and leucine (P : 0.004 and 0.012, respectively). FPG was positively associated with intake of all amino acids except for cysteine, glutamic acid, threonine, leucine and histidine. CONCLUSION: In the present study, the pattern of relationships between dietary intake of amino acids and serum lipid profile and BP has been described among people with SCI. PMID- 26679400 TI - Oral tacrolimus for the treatment of generalized morphea. PMID- 26679401 TI - Challenging compounds for calculating molecular second hyperpolarizabilities: the triplet state of the trimethylenemethane diradical and two derivatives. AB - The second hyperpolarizability gamma of trimethylenemethane (TMM) and two 1,3 dipole derivatives (NXA and OXA) in their triplet ground state has been evaluated at the UCCSD(T) level with the d-aug-cc-pVDZ extended basis set, highlighting that gamma decreases from TMM to NXA and OXA, following the opposite order of their permanent dipole moments. These results are then used to benchmark a broad range of levels of approximation. So, the UMP2, UMP4, and UCCSD methods can be used to characterize gamma of TMM and NXA but not of OXA. In that case, the large field-induced charge transfer contribution is difficult to handle using the MPn methods and only the UCCSD method provides values close to the UCCSD(T) reference. Turning to the performance of DFT with typical exchange-correlation functionals, the UM06-2X functional, which contains 54% of HF exchange, performs very well with a maximum of 4.5% of difference with respect to the reference values. On the other hand, employing less HF exchange leads to an overestimation of the responses whereas range-separated hybrids generally underestimate the second hyperpolarizabilities. Finally, the use of spin-projected methods for these 1,3-dipole triplet molecules has a little impact since the spin contamination is almost negligible. PMID- 26679402 TI - How many OPV rounds are required to stop wild polio virus circulation in a developed country? Lessons from the Israeli experience. PMID- 26679403 TI - Affluence as a predictor of vaccine refusal and underimmunization in California private kindergartens. AB - BACKGROUND: Non-medical vaccine exemption rates in California private schools far exceed those of public schools, but little is known about specific factors which may be associated with high exemption rates in private schools. METHODS: The percent of personal-belief exemptions (PBEs) among California public and private kindergartens were computed for 2000-2001 to 2014-2015 academic years. For the 2014-2015 academic year, a random sample of private schools was selected to investigate associations between kindergarten characteristics (tuition amount, religious affiliation) and vaccine profile (non-medical vaccine exemptions, vaccine coverage). RESULTS: The proportion of private kindergartens reporting 5% or more children with PBEs increased from 9% (2000-2001) to 34% (2013-2014), followed by a small decrease in 2014-2015 (31%). Overall, 93.7% (565/605) of kindergartens sampled in 2014-2015 had data available. Very high PBE levels (>20%) were seen among secular and non-Catholic, Christian kindergartens but not Roman Catholic, Jewish or Islamic kindergartens. However, the majority of schools at all tuition levels had fewer than 5% of children with a PBE. Kindergartens with an annual tuition of $10,000 or more were over twice as likely to have 20% or more children with PBEs than kindergartens with a lower tuition (p<.01). Additionally, the conditional admission proportions for kindergartens with tuitions of $10,000 or more were 39% compared to 22% for less expensive kindergartens (p<.01). Only about half of all private kindergartens had 95% coverage of the MMR (49%) and pertussis-containing vaccines (51%). CONCLUSIONS: School-entry vaccination requirements are critical to preventing outbreaks of vaccine preventable diseases in the US. Nonmedical exemptions increased between the 2000-2001 and 2014-2015 academic years and appear to be associated with affluence, raising social justice concerns. PMID- 26679404 TI - Signal reachability facilitates characterization of probabilistic signaling networks. AB - BACKGROUND: Studying biological networks is of extreme importance in understanding cellular functions. These networks model interactions between molecules in each cell. A large volume of research has been done to uncover different characteristics of biological networks, such as large-scale organization, node centrality and network robustness. Nevertheless, the vast majority of research done in this area assume that biological networks have deterministic topologies. Biological interactions are however probabilistic events that may or may not appear at different cells or even in the same cell at different times. RESULTS: In this paper, we present novel methods for characterizing probabilistic signaling networks. Our methods do this by computing the probability that a signal propagates successfully from receptor to reporter genes through interactions in the network. We characterize such networks with respect to (i) centrality of individual nodes, (ii) stability of the entire network, and (iii) important functions served by the network. We use these methods to characterize major H. sapiens signaling networks including Wnt, ErbB and MAPK. PMID- 26679405 TI - Light-Powered Self-Healable Metallosupramolecular Soft Actuators. AB - Supramolecular functional materials able to respond to external stimuli have several advantages over their classical covalent counterparts. The preparation of soft actuators with the ability to respond to external stimuli in a spatiotemporal fashion, to self-repair, and to show directional motion, is currently one of the most challenging research goals. Herein, we report a series of metallopolymers based on zinc(II)-terpyridine coordination nodes and bearing photoisomerizable diazobenzene units and/or solubilizing luminescent phenylene ethynylene moieties. These supramolecular polymers act as powerful gelating agents at low critical gelation concentrations. The resulting multiresponsive organogels display light-triggered mechanical actuation and luminescent properties. Furthermore, owing to the presence of dynamic coordinating bonds, they show self-healing abilities. PMID- 26679406 TI - Literacy and motivation for the prevention and control of hypertension among female community health volunteers: a qualitative study from Nepal. AB - BACKGROUND: The prevalence of hypertension is increasing in Nepal. Thus, there is a need for a programme to improve primary healthcare. One possibility is to assign prevention, diagnosis, and treatment of hypertension to female community health volunteers (FCHVs). OBJECTIVE: To assess literacy and motivation to be involved in a hypertension prevention and control programme in Nepal among FCHVs. DESIGN: Five focus group discussions (FGDs) were conducted with a total of 69 FCHVs in Lekhnath municipality, Kaski district, Nepal. Seven themes were developed on the basis of data collection: 1) knowledge about hypertension; 2) risk factors of hypertension; 3) prevention and control of hypertension; 4) access to treatment for hypertension in the community; 5) learning about blood pressure measurement; 6) ability to raise blood pressure awareness in the community; 7) possible challenges for their future involvement. Data were analysed using the thematic analysis approach. RESULTS: FCHVs have some knowledge about diagnosis, risk factors, and complications of hypertension. General unanimity was observed in the understanding that hypertension and risk factors needed to be addressed. The willingness of FCHVs to contribute to prevention, control, and management was strong, and they were confident that with some basic training they could obtain skills in hypertension management. CONCLUSIONS: Despite limited knowledge about hypertension, FCHVs expressed willingness and readiness to be trained in hypertension management. This study supports the possibility of involving FCHVs in prevention and control of hypertension in Nepal. PMID- 26679407 TI - Evaluating the cost of adult voluntary medical male circumcision in a mixed (surgical and PrePex) site compared to a hypothetical PrePex-only site in South Africa. AB - BACKGROUND: Several circumcision devices have been evaluated for a safe and simplified male circumcision among adults. The PrePex device was prequalified for voluntary male medical circumcision (VMMC) in May 2013 by the World Health Organization and is expected to simplify the procedure safely while reducing cost. South Africa is scaling up VMMC. OBJECTIVE: To evaluate the overall unit cost of VMMC at a mixed site vs. a hypothetical PrePex-only site in South Africa. DESIGN: We evaluated the overall unit cost of VMMC at a mixed site where PrePex VMMC procedure was added to routine forceps-guided scalpel-based VMMC in Soweto, South Africa. We abstracted costs and then modeled these costs for a hypothetical PrePex-only site, at which 9,600 PrePex circumcisions per year could be done. We examined cost drivers and modeled costs, varying the price of the PrePex device. The healthcare system perspective was used. RESULTS: In both sites, the main contributors of cost were personnel and consumables. If 10% of all VMMC were by PrePex at the mixed site, the overall costs of the surgical method and PrePex were similar - US$59.62 and $59.53, respectively. At the hypothetical PrePex-only site, the unit cost was US$51.10 with PrePex circumcisions having markedly lower personnel and biohazardous waste management costs. In sensitivity analysis with the cost of PrePex kit reduced to US$10 and $2, the cost of VMMC was further reduced. CONCLUSIONS: Adding PrePex to an existing site did not necessarily reduce the overall costs of VMMC. However, starting a new PrePex-only site is feasible and may significantly reduce the overall cost by lowering both personnel and capital costs, thus being cost-effective in the long term. Achieving a lower cost for PrePex will be an important contributor to the scale-up of VMMC. PMID- 26679408 TI - Factors affecting adoption, implementation fidelity, and sustainability of the Redesigned Community Health Fund in Tanzania: a mixed methods protocol for process evaluation in the Dodoma region. AB - BACKGROUND: Despite the implementation of various initiatives to address low enrollment in voluntary micro health insurance (MHI) schemes in sub-Saharan Africa, the problem of low enrollment remains unresolved. The lack of process evaluations of such interventions makes it difficult to ascertain whether their poor results are because of design failures or implementation weaknesses. OBJECTIVE: In this paper, we describe a process evaluation protocol aimed at opening the 'black box' to evaluate the implementation processes of the Redesigned Community Health Fund (CHF) program in the Dodoma region of Tanzania. DESIGN: The study employs a cross-sectional mixed methods design and is being carried out 3 years after the launch of the Redesigned CHF program. The study is grounded in a conceptual framework which rests on the Diffusion of Innovation Theory and the Implementation Fidelity Framework. The study utilizes a mixture of quantitative and qualitative data collection tools (questionnaires, focus group discussions, in-depth interviews, and document review), and aligns the evaluation to the Theory of Intervention developed by our team. Quantitative data will be used to measure program adoption, implementation fidelity, and their moderating factors. Qualitative data will be used to explore the responses of stakeholders to the intervention, contextual factors, and moderators of adoption, implementation fidelity, and sustainability. DISCUSSION: This protocol describes a systematic process evaluation in relation to the implementation of a reformed MHI. We trust that the theoretical approaches and methodologies described in our protocol may be useful to inform the design of future process evaluations focused on the assessment of complex interventions, such as MHI schemes. PMID- 26679409 TI - Effects of Cardiovascular Events on End-Stage Renal Disease and Mortality in Patients With Chronic Kidney Disease Before Dialysis. AB - Cardiovascular events (CVEs) are major complications in patients with chronic kidney disease (CKD). However, few studies have investigated the effects of CVEs on end-stage renal disease (ESRD) and mortality of pre-dialysis patients. We followed 377 CKD patients who were at stage >=G3 at first clinic visit in the Shuuwa General Hospital between April 2005 and July 2014. After taking baseline patient data, we evaluated renal survival rates and all-cause and CVE-related mortality in patients with CVEs [(+)CVEs] and without CVEs [(-)CVEs]. A total of 99 CVEs occurred in 93 study patients (57.0% cardiac events, 43.0% cerebrovascular events, and 6.5% peripheral artery disease events). During the study period, 127 patients reached ESRD over a median of 4.51 years' follow-up. Kaplan-Meier analysis found longer renal survival rates in the (-)CVEs group compared with the (+)CVEs group. Forty patients died during the study period over a median of 5.43 years' follow-up. Survival rates for all-cause and CVE-related mortality of (-)CVEs patients were higher than in (+)CVEs patients. After adjustment for sex, age, current smoking, blood pressure, diabetes, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, left ventricular hypertrophy, body mass index, albumin, hemoglobin, calcium, phosphate, C-reactive protein, and spot urine protein, the occurrence of CVEs was still a significant risk factor for ESRD (HR 1.516, P = 0.017) and all-cause mortality (HR 7.871, P < 0.001). Our findings suggest that the occurrence of CVEs is a potent risk factor for ESRD and mortality in CKD patients before dialysis. PMID- 26679411 TI - First Do No Harm in End-of-Life Care: A Comment on the 2015 American Heart Association Guidelines for Post-Resuscitation Care of Cardiopulmonary Arrest. PMID- 26679410 TI - Inhibition of growth and induction of apoptosis in A549 cells by compounds from oxheart cabbage extract. AB - BACKGROUND: Oxheart cabbage (Brassica oleracea var. capitata) is a member of the Brassica genus. Although some studies on the anticancer effects of extracts from oxheart cabbage have been reported, comprehensive information on the bioactive fractions and components from oxheart cabbage extracts is still lacking. The aim of this study was to isolate and identify the bioactive fractions and components from oxheart cabbage seeds using activity-guided isolation methods. RESULTS: The cytotoxicity and apoptotic effects of fraction II, fraction III, iberverin, sulforaphane and iberin from oxheart cabbage seed extract were investigated. The results showed that all five components had inhibitory effects on the in vitro growth of A549 cells which were dose-dependent. These compounds also changed the morphology of A549 cells, and their inhibitory activity on A549 cells was as follows: sulforaphane > iberin > iberverin > fraction III > fraction II. The IC50 values were 3.53 +/- 0.63, 4.93 +/- 1.02, 7.07 +/- 0.51, 15.56 +/- 0.24 and 27.32 +/- 0.63 ug mL(-1) respectively. Fraction II, fraction III, iberverin, sulforaphane and iberin induced cell apoptosis by increasing early apoptosis and late apoptosis/necrosis, and activation of caspase-3, -8 and -9. CONCLUSION: These results indicated that the decrease in A549 cell viability by active compounds from oxheart cabbage seed extract was due to the induction of apoptosis. (c) 2015 Society of Chemical Industry. PMID- 26679412 TI - GIW and InCoB, two premier bioinformatics conferences in Asia with a combined 40 years of history. AB - Knowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016. PMID- 26679415 TI - Maternal HIV infection alters the immune balance in the mother and fetus; implications for pregnancy outcome and infant health. AB - PURPOSE OF REVIEW: With the rapid roll-out of combination antiretroviral therapy to prevent mother-to-child transmission of HIV, there is an annual increase in the number of uninfected infants born to HIV-infected women. Although the introduction of combination antiretroviral therapy has vastly improved pregnancy outcome and the health of infants born to HIV-infected women, concerns remain regarding the impact the maternal HIV infection on the pregnancy outcome and the health of HIV-exposed uninfected infants. RECENT FINDINGS: Maternal HIV infection is associated with negative pregnancy outcomes such as low birth weight. In addition, an increased susceptibility to infections is reported in HIV-exposed uninfected infants compared with infants born to uninfected women. Studies have shown that HIV-exposure affects the maternal/fetal unit, with increase of proinflammatory cytokine produced by placental cells, as well as altered infant immune responses. These changes could provide the underlying conditions for negative pregnancy outcomes and facilitate mother-to-child transmission of HIV in the infant. Further studies are required to understand the underlying mechanisms and investigate whether these altered infant immune responses persist and have clinical consequences beyond childhood. SUMMARY: HIV infection in pregnant women is associated with altered immune responses in HIV-infected women and their offspring with clinical consequences for pregnancy outcome and the HIV-exposed uninfected infant. Further studies are required to address the origin and long term consequences of prenatal HIV-exposure and subsequent immune activation for infant health. PMID- 26679413 TI - Immune activation and paediatric HIV-1 disease outcome. AB - PURPOSE OF REVIEW: The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced, whereas access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems observed in adult infection resulting from chronic inflammation triggered by persistent immune activation even following ART mediated suppression of viral replication are magnified in children infected from birth. RECENT FINDINGS: Features of immune ontogeny favour low immune activation in early life, whereas specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naive nonprogressing children exists in whom normal CD4 cell counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with nonprogressing adult infection which is characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, which ultimately influence disease outcome, are discussed. SUMMARY: Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV. PMID- 26679414 TI - Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. AB - PURPOSE OF REVIEW: This article describes the mechanisms and consequences of both microbial translocation and microbial dysbiosis in HIV infection. RECENT FINDINGS: Microbes in HIV are likely playing a large role in contributing to HIV pathogenesis, morbidities and mortality. Two major disruptions to microbial systems in HIV infection include microbial translocation and microbiome dysbiosis. Microbial translocation occurs when the bacteria (or bacterial products) that should be in the lumen of the intestine translocate across the tight epithelial barrier into systemic circulation, where they contribute to inflammation and pathogenesis. This is associated with poorer health outcomes in HIV-infected individuals. In addition, microbial populations in the gastrointestinal tract are also altered after HIV infection, resulting in microbiome dysbiosis, which further exacerbates microbial translocation, epithelial barrier disruption, inflammation and mucosal immune functioning. SUMMARY: Altered microbial regulation in HIV infection can lead to poor health outcomes, and understanding the mechanisms underlying microbial dysbiosis and translocation may result in novel pathways for therapeutic interventions. PMID- 26679416 TI - CD4 T-cell hyporesponsiveness induced by schistosome larvae is not dependent upon eosinophils but may involve connective tissue mast cells. AB - In areas endemic for schistosomiasis, people can often be in contact with contaminated water resulting in repeated exposures to infective Schistosoma mansoni cercariae. Using a murine model, repeated infections result in IL-10 dependent CD4(+) T-cell hyporesponsiveness in the skin-draining lymph nodes (sdLN), which could be caused by an abundance of eosinophils and connective tissue mast cells at the skin infection site. Here, we show that whilst the absence of eosinophils did not have a significant effect on cytokine production, MHC-II(+) cells were more numerous in the dermal cell exudate population. Nevertheless, the absence of dermal eosinophils did not lead to an increase in the responsiveness of CD4(+) T cells in the sdLN, revealing that eosinophils in repeatedly exposed skin did not impact on the development of CD4(+) T-cell hyporesponsiveness. On the other hand, the absence of connective tissue mast cells led to a reduction in dermal IL-10 and to an increase in the number of MHC II(+) cells infiltrating the skin. There was also a small but significant alleviation of hyporesponsiveness in the sdLN, suggesting that mast cells may have a role in regulating immune responses after repeated exposures of the skin to S. mansoni cercariae. PMID- 26679417 TI - Loss of fractal gait harmony in Parkinson's Disease. AB - OBJECTIVE: Recently, an intrinsic fractal harmonic structure was found underlying the rhythm of physiological walking, but it has not yet been investigated in subjects with a neurological disease. The aim of this study was to determine if and how this harmonic structure is altered in patients with Parkinson's Disease. METHODS: Gait analysis of 70 patients with Parkinson's Disease in pharmacological phase on was performed, the findings of which we compared with reference data of age-matched healthy subjects. Fifteen patients were retested after a washout period of 12 h. RESULTS: Alterations in all spatio-temporal gait parameters and gait indices with regard to symmetry, coordination, and harmony were noted, but after correction for multicollinearity bias, only the latter correlated significantly with Unified Parkinson's Disease Rating Scale motor score (p=0.001). The fractal gait structure underwent even more extensive alterations in pharmacological off phase (p<0.05). CONCLUSIONS: The intrinsic gait harmony was altered in patients with Parkinson's Disease and significantly correlated to motor severity. It could be partially recovered by assumption of L-dopa. SIGNIFICANCE: Loss of harmony is a quantitatively assessable gait benchmark in Parkinson's Disease. It seems to be dependent on dopaminergic but also on non dopaminergic networks. PMID- 26679418 TI - Cortical activity after stimulation of the corticospinal tract in the spinal cord. AB - OBJECTIVE: Intraoperative electrical stimulation of the spinal cord evokes not only high amplitude cortical somatosensory evoked potentials (ScEPs: spinal cord evoked potentials) recorded from the scalp but also early potentials. It has been postulated that the early potential recorded from the scalp could be generated by antidromic stimulation of the cortico-spinal tract (ACSP: Antidromic Corticospinal tract Potential or "anti D-wave"). In this study, we aimed to investigate the anti D-wave evoked by epidural stimulation in a population of neurologically uncompromised/compromised patients during spine and spinal cord surgery. To better define its origin, we examined its spatial distribution, response to stimulation modification and recording parameters, and finally, we correlated anti D-waves and corresponding epidural recorded D-waves after a transcranial electric stimulation at the same level of spinal cord stimulation. METHODS: Tibial nerve somatosensory evoked potentials (SEPs), transcranially elicited muscle motor evoked potentials (m-MEPs), epidural motor evoked potentials (D-wave), and cortical spinal cord-evoked potentials (ScEPs) as well as Antidromic Cortico Spinal tract Potential (anti D-wave) were intraoperatively recorded in 30 subjects with different degrees of neurological involvement. ScEPs and anti D-wave were evoked by epidural stimulation of the spinal cord, both cranially and caudally to the surgery site and were recorded over the scalp at the midline. The effects of the stimulus rate and high pass filter were also tested. RESULTS: The anti D-wave was recordable in all neurologically intact patients and was clearly isolated from the ScEPs by its very short latency; recordings of the anti D-wave were limited to the anterior midline, and its amplitude was only slightly reduced by increasing the stimulus rate or by changing the high pass filter, and its latency was slightly longer than that of the D-wave latency. In neurologically compromised patients, the anti D-wave and D wave exhibit a similar behaviour, both of which were present in neurologically intact or moderately compromised patients and absent in patients with quadri/paraplegia. In a patient with paraplegia due to T8 meningioma and in neurologically intact patients in whom the cauda/conus stimulated the anti D wave, cortical ScEPs were absent when the stimulation was performed caudally to the surgical site. CONCLUSIONS: We provide evidence that the anti D-wave behaviour and its parameters have a close correlation with the behaviour of the D wave; specifically, its distribution, response to filtering, stimulus rate, and absence in paraplegic patients. SIGNIFICANCE: The presented data demonstrate that the anti D-wave is generated by the antidromic stimulation of fast neurons of the corticospinal tract, and consistent findings have been previously published in animals. PMID- 26679419 TI - What do we learn from the influence of motor activities on the after-effect of non-invasive brain stimulation? PMID- 26679420 TI - Language mapping using high gamma electrocorticography, fMRI, and TMS versus electrocortical stimulation. AB - OBJECTIVE: The aim of the present study was to compare localization of the language cortex using cortical stimulation mapping (CSM), high gamma electrocorticography (hgECoG), functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS). METHODS: Language mapping using CSM, hgECoG, fMRI, and TMS were compared in nine patients with epilepsy. Considering CSM as reference, we compared language mapping approaches based on hgECoG, fMRI, and TMS using their sensitivity, specificity, and the results of receiver operating characteristic (ROC) analyses. RESULTS: Our results show that areas involved in language processing can be identified by hgECoG, fMRI, and TMS. The average sensitivity/specificity of hgECoG, fMRI, and TMS across all patients was 100%/85%, 50%/80%, and 67%/66%, respectively. The average area under the ROC curve of hgECoG, fMRI, and TMS across CSM-positive patients was 0.98, 0.76, and 0.68, respectively. CONCLUSIONS: There is considerable concordance between CSM, hgECoG, fMRI, and TMS language mapping. Our results reveal that hgECoG, fMRI, and TMS are valuable tools for presurgical language mapping. SIGNIFICANCE: Language mapping on the basis of hgECoG, fMRI, and TMS can provide important additional information, therefore, these methods can be used in conjunction with CSM or as an alternative, when the latter is deemed impractical. PMID- 26679421 TI - Rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' in critically ill neurological patients. AB - OBJECTIVES: To study periodic and rhythmic EEG patterns classified according to Standardized Critical Care EEG Terminology (SCCET) of the American Clinical Neurophysiology Society and their relationship to electrographic seizures. METHODS: We classified 655 routine EEGs in 371 consecutive critically ill neurological patients into (1) normal EEGs or EEGs with non-specific abnormalities or interictal epileptiform discharges, (2) EEGs containing unequivocal ictal EEG patterns, and (3) EEGs showing rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIIU) according to SCCET. RESULTS: 313 patients (84.4%) showed normal EEGs, non-specific or interictal abnormalities, 14 patients (3.8%) had EEGs with at least one electrographic seizure, and 44 patients (11.8%) at least one EEG containing RPPIIIU, but no EEG with electrographic seizures. Electrographic seizures occurred in 11 of 55 patients (20%) with RPPIIIU, but only in 3 of 316 patients (0.9%) without RPPIIIU (p?0.001). Conversely, we observed RPPIIIU in 11 of 14 patients (78.6%) with electrographic seizures, but only in 44 of 357 patients (12.3%) without electrographic seizures (p?0.001). CONCLUSIONS: On routine-EEG in critically ill neurological patients RPPIIIU occur 3 times more frequently than electrographic seizures and are highly predictive for electrographic seizures. SIGNIFICANCE: RPPIIIU can serve as an indication for continuous EEG recordings. PMID- 26679423 TI - Six-Year Checkup: Narrowing the Scope of Practical Radiation Oncology. PMID- 26679422 TI - Three easy pieces. AB - BACKGROUND: Differential scanning calorimetry is a powerful method that provides a complete thermodynamic characterization of the stability of a protein as a function of temperature. There are, however, circumstances that preclude a complete analysis of DSC data. The most common ones are irreversible denaturation transitions or transitions that take place at temperatures that are beyond the temperature limit of the instrument. Even for a protein that undergoes reversible thermal denaturation, the extrapolation of the thermodynamic data to lower temperatures, usually 25 degrees C, may become unreliable due to difficulties in the determination of DeltaCp. METHODS: The combination of differential scanning calorimetry and isothermal chemical denaturation allows reliable thermodynamic analysis of protein stability under less than ideal conditions. RESULTS AND CONCLUSIONS: This paper demonstrates how DSC can be used in combination with chemical denaturation to address three different scenarios: 1) estimation of an accurate DeltaCp value for a reversible denaturation using as a test system the envelope HIV-1 glycoprotein gp120; 2) determination of the Gibbs energy of stability in the region in which thermal denaturation is irreversible using HEW lysozyme at different pH values; and, 3) determination of Gibbs energy of stability for a thermostable protein, thermolysin. PMID- 26679425 TI - The Use of Novel Oral Anticoagulants in Adult Congenital Heart Disease: A Single Center Experience. PMID- 26679424 TI - Efficacy and Safety of Long-Acting Reversible Contraception in Women With Cardiovascular Conditions. AB - The physiological changes that occur during pregnancy can be deleterious to women with a cardiovascular condition. Evidence-based contraceptive counseling and provision is essential in this patient population. Although long-acting reversible contraception (LARCs), which include the intrauterine device (IUD) and the etonogestrel contraceptive implant, have been found to be safe and effective in healthy women, there are inadequate data regarding LARC use in patients with cardiovascular conditions. We conducted a retrospective chart review of women diagnosed with cardiovascular disease who had a copper IUD, levonorgestrel releasing intrauterine system or contraceptive implant placed at the University of Washington Medical Center from 2007 to 2012. We abstracted and analyzed patient demographic characteristics, medical conditions, indications for LARC placement, and complications. The sample included 470 women with cardiovascular conditions. The mean age was 34.6 years. One hundred twenty-four patients (26.11%) were nulligravid and 169 patients (35.58%) were nulliparous. Four hundred ten chose the levonorgestrel-releasing intrauterine system (87.23%), 33 patients (7.02%) opted for the copper IUD, and 23 patients (4.89%) chose the etonogestrel implant. Eighteen patients (3.83%) had a confirmed IUD expulsion, 2 patients (0.43%) became pregnant, and there were 4 cases of pelvic inflammatory disease (0.85%). There were no cases of perforation. There were no confirmed cases of infective endocarditis associated with LARC insertion. In conclusion, LARC devices appear safe with few complications for women with cardiovascular conditions. Clinicians can be reassured that LARC may be offered as an appropriate option when counseling women with cardiovascular disease on safe contraceptive methods. PMID- 26679426 TI - Molecular dynamics simulation strategies for protein-micelle complexes. AB - The structure and stability of membrane proteins can vary widely in different detergents and this variability has great practical consequences for working with membrane proteins. Nevertheless, the mechanisms that operate to alter the behavior of proteins in micelles are poorly understood and not predictable. Atomic simulations could provide considerable insight into these mechanisms. Building protein-micelle complexes for simulation is fraught with uncertainty, however, in part because it is often unknown how many detergent molecules are present in the complex. Here, we describe several convenient ways to employ Micelle Builder in CHARMM-GUI to rapidly construct protein-micelle complexes and performed simulations of the isolated voltage-sensor domain of voltage-dependent potassium-selective channel and an antimicrobial peptide papiliocin with varying numbers of detergents. We found that once the detergent number exceeds a threshold, protein-detergent interactions change very little and remain very consistent with experimental observations. Our results provide a platform for future studies of the interplays between protein structure and detergent properties at the atomic level. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26679427 TI - The assembly and annotation of the complete Rufous-bellied thrush mitochondrial genome. AB - Among known bird species, oscines are one of the few groups that produce complex vocalizations due to vocal learning. One of the most conspicuous oscine passerines in southeastern South America is the Rufous-bellied Thrush, Turdus rufiventris. The complete mitochondrial genome of this species was sequenced with the Illumina HiSeq platform (Illumina Inc., San Diego, CA), assembled using MITObim software and annotated by MITOS web server and Artemis software. This mitogenome contained 16 669 bases, organized as 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and a control region (d-loop). The sequencing of the Rufous-bellied Thrush mitochondrial genome is of particular interest for better understanding of population genetics and phylogeography of the Turdidae family. PMID- 26679428 TI - The Effects of Service-Learning on College Students' Attitudes Toward Older Adults. AB - The current U.S. health care workforce shortage is at crisis levels for providers who specialize in elder care. Barriers such as ageism, lack of awareness of the need for workers, and lack of contact with seniors can affect the career choice of young professionals. To explore ways to increase the number of students who pursue gerontology and to expand the elder care workforce, the researchers conducted a qualitative content analysis on the impact of service learning in senior care facilities on students' attitudes toward older adults. Students with senior contact reported increases in positive perceptions of seniors, discovered their own ageist stereotypes, and developed an interest in a career in elder care. Twenty-one months after the service-learning experience, students were surveyed again with their responses indicating continued positive attitude changes along with professional development demonstrating beneficial long-term effects from the experience. PMID- 26679429 TI - Toxicity to Diaphania hyalinata, selectivity to non-target species and phytotoxicity of furanones and phthalide analogues. AB - BACKGROUND: Despite being of great importance to crop protection, the disadvantages of intensive and inappropriate use of pesticides have stimulated the search for more selective and less harmful agrochemicals. Thus, we have evaluated the effectiveness of 16 synthetic molecules (phthalides and precursors) to control the melonworm Diaphania hyalinata, a key pest in cucurbit crops of economic importance in Brazil. The selectivity to beneficial organisms Solenopsis saevissima and Tetragonisca angustula and the phytotoxicity to Cucumis sativus of the promising insecticides were also assessed. RESULTS: In the screening assay, compounds 1 and 6 provided 91 and 88% mortality of the melonworm. Compound 1 presented higher toxicity (median lethal dose LD50 = 15.99 umol g(-1) ) and higher speed on pest control (median survival time LT50 = 420 min) than compound 6 (LD50 = 44.51 umol g(-1) and LT50 = 840 min). Both compounds inhibited less than 11% of host-plant growth and caused <=36 and >=93% mortality of predator and pollinator respectively. CONCLUSION: Among the tested compounds, only compounds 1 and 6 were effective in melonworm control. Both compounds presented no considerable phytotoxicity and were selective to predator but non-selective to pollinator, which enables their application for pest control if the exposure of the bees is minimised. (c) 2015 Society of Chemical Industry. PMID- 26679430 TI - Vortioxetine: a New Treatment for Major Depressive Disorder. AB - INTRODUCTION: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug's effects from those of current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). AREAS COVERED: This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE database literature search in August 2015 using the key search terms, vortioxetine and Lu AA21004, combined with additional terms that included pharmacological profile, pharmacokinetics, drug interactions, adverse effects, side effects, safety, major depression, and major depressive disorder. We identified relevant systematic reviews, meta-analyses, randomized trials and preclinical studies of importance. EXPERT OPINION: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first line antidepressant option. PMID- 26679431 TI - ISO 12189 standard for the preclinical evaluation of posterior spinal stabilization devices--I: Assembly procedure and validation. AB - The International Standardization Organization introduced standard 12189 for the preclinical evaluation of the mechanical reliability of posterior stabilization devices. The well-known vertebrectomy model formalized in standard F1717 by the American Society for Testing and Materials was modified with the introduction of a modular anterior support made up of three calibrated springs, which allows to describe a more realistic scenario, closer to the effective clinical use, as well to test even very flexible and dynamic posterior stabilization implants. Despite these important improvements, ISO 12189 received very little attention in the literature. The aim of the work is to provide a systematic procedure for the assembly and validation of a finite element model capable of describing the experimental test according to ISO 12189. The validated finite element model is able to catch very well the effective stiffness of the unassembled and assembled constructs (percentage differences <2% and <10%, respectively). As concern the assembled construct, the experimentally measured and predicted strains were found in a good agreement (R2 > 0.75, root mean square error < 30%), but the procedure without precompression lead to much better results (R2 > 0.96, root mean square error < 10%). Given the prediction errors of the assembled construct fall within the experimental range of repeatability, the finite element model can be systematically implemented to support the mechanical design of a variety of spinal implants, to quantitatively investigate the load-sharing mechanism, as well as to investigate the loading conditions set by ISO 12189 standard. PMID- 26679433 TI - Effect of cryopreservation technique and season on the survival of in vitro produced cattle embryos. AB - Embryo cryopreservation is a major tool for conservation and propagation of genetically superior animals. However, it adversely affects the survival of embryos. The objective of this study was to determine the effects of cryopreservation technique (vitrification compared with slow freezing) and different seasons in which oocytes were obtained on the post-warming survival of in vitro produced (IVP) cattle morulae. In experiment 1, morulae (Day 6 post IVF), obtained from abattoir-sourced oocytes during spring, summer, fall and winter over a period of 3.5 years, were subjected to either vitrification (n=271 morulae), slow freezing (n=281 morulae) or no freezing (control; n=249 morulae). After warming, the morulae were cultured to the expanded blastocyst stage (Day 8 post-IVF). Data were compared using Glimmix procedure in SAS((r)). Blastocyst rate differed (P<0.05) among the treatments: unfrozen control (78+/-3.6%), vitrification (52+/-4.6%) and slow freezing (35+/-4.2%). The re-expansion of vitrified morulae upon warming was not correlated with subsequent blastocyst rate (r=-0.048; P>0.05). The morulae produced during fall season had lesser (P<0.05) cleavage and morula rates (67+/-1.6%; Day 2 post-IVF and 22+/-1.4%; Day 6 post IVF, respectively) than all other seasons (74+/-1.1 and 30+/-1.2%, respectively). Blastocyst rate was the least (P<0.05) when oocytes were collected during the summer season in both control and slowly frozen groups. Blastocyst development rate did not change due to season in vitrification group (P>0.05). In conclusion, vitrification is a more desirable technique than slow freezing for cryopreservation of IVP cattle morulae. If the slow freezing method is employed, greater success can be achieved using oocytes collected in the winter and spring with a primary contributing factor being lesser morulae development if oocytes are collected in the fall and also the lesser blastocyst formation of cryopreserved morulae when oocytes are collected in the summer. PMID- 26679432 TI - Gut barrier impairment by high-fat diet in mice depends on housing conditions. AB - SCOPE: Diet-induced obesity (DIO) is proposed to cause impairments in intestinal barrier integrity, but contradictory results have been published and it appears that the outcomes depend on other environmental factors. We therefore assessed whether the hygienic status of animal facilities alters the gut barrier in DIO mice. METHODS AND RESULTS: Male C57BL/6N mice were housed in a conventional (CV) or a specific pathogen-free (SPF) animal facility and were fed identical diets represented by a high-fat (60kJ% fat) or control diet (11kJ% fat) for 12 wks. Intestinal barrier function in small and large intestine was evaluated in Ussing chambers by electrical resistance and permeability measurements. Jejunal (p < 0.01) and proximal colonic (p < 0.05) barrier function was altered in CV DIO mice, but not in SPF DIO mice. Moreover, only CV DIO mice were characterized by metabolic endotoxemia and low-grade inflammation. High-throughput 16S rRNA gene sequencing revealed significant differences in fecal bacterial diversity and composition between the two animal facilities, but only in mice fed the HFD. Moreover, cecal DCA concentrations correlated positively with two yet uncultivated Clostridiales species. CONCLUSIONS: We demonstrated that housing conditions and associated changes in gut bacterial colonization are pivotal for maintenance of gut barrier integrity in DIO mice. PMID- 26679434 TI - The mechanism of regulation of ovarian maturation by red pigment concentrating hormone in the mud crab Scylla paramamosain. AB - In this study a full-length cDNA (Sp-RPCH) was cloned from the eyestalk ganglia of the mud crab Scylla paramamosain. Sp-RPCH is 660 base pairs in length and its open reading frame encodes a precursor that is predicted to be processed into a 25-residue signal peptide, a mature red pigment concentrating hormone (RPCH, an octapeptide), and a 75-residue precursor-related peptide. Phylogenetic analysis indicates that it clusters with other crustacean RPCHs and belongs to the adipokinetic hormone/RPCH peptide superfamily. Sp-RPCH gene expression was detected, using an end-point polymerase chain reaction (PCR), not only in the eyestalk ganglia but also in the brain and thoracic ganglia. Quantified using a real-time PCR, Sp-RPCH gene expression levels in the three tissues fluctuated along a cycle of ovarian maturation, with the levels progressively increased from stages I to IV, after which the expression levels decreased (although they remained significantly higher than stage I levels) when the ovary reached the mature stage (stage V). It was demonstrated using a patch clamp analysis that synthetic RPCH was able to evoke a Ca(2+) current in dissociated brain neurons and synthetic RPCH significantly increased the mean oocyte diameter of the ovarian tissues co-cultured with the eyestalk ganglia, brain, or thoracic ganglia; the stimulatory effect of RPCH was absent when the nervous tissues were not included in the ovarian incubation. Animals administrated with RPCH had significantly higher levels of gonad-somatic index, hepatopancreas-somatic index, and vitellogenin gene expression, when compared to control animals receiving a saline injection. The combined results clearly show that RPCH is involved in ovarian maturation in the mud crab; the stimulatory effects of RPCH are likely mediated by its actions on the release from the nervous tissues of factor(s) that directly regulate vitellogenesis in the ovary and hepatopancreas. PMID- 26679436 TI - The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data. AB - PURPOSE: To evaluate the effect of chronic mild hyponatremia ([Na+]=130 137mmol/L) on bone mineral content (BMC) and bone mineral density (BMD) loss through multiple, serial dual-energy X-ray absorptiometry (DXA) scans. METHODS: Utilizing biochemical and DXA scan data from two Danish regions between 2004 and 2011, supplemented with national Danish patient diagnosis and prescription reimbursement databases, a retrospective cohort study was performed. All subjects with more than one DXA scan were included, then stratified into "normonatremia" ([Na(+)]=[137.00-147.00] mmol/L) and "mild hyponatremia" ([Na(+)]=[130.00 137.00[mmol/L) based on mean and confidence interval (CI) values calculated from all plasma sodium measurements between each subject's first and last DXA scan. Baseline, follow-up and delta values for hip and lumbar spine BMC and BMD were estimated between groups, then adjusted for comorbidity and medication use. RESULTS: Hip and lumbar spine groups had 884 and 1069 patients with "normonatremia" versus 58 and 58 patients with "mild hyponatremia", respectively. Mild hyponatremia was associated with lower BMC and BMD in nearly all regions of the hip, and with worse losses in the trochanteric, femoral neck and total hip regions. Mild hyponatremia had limited effect on the lumbar spine. CONCLUSIONS: Chronic mild hyponatremia seems to greatly affect bone in the hip, while the effect is limited in the lumbar spine. We suggest further retrospective study of patients with moderate (P-Na=120-130mmol/L) to severe hyponatremia (P Na<120mmol/L) and prospective studies to further examine the association. PMID- 26679435 TI - The effects of bariatric surgery on bone and nephrolithiasis. AB - The impact of bariatric surgery on cardiovascular and diabetic complications associated with an improvement in survival has overshadowed the adverse skeletal health and development of kidney stone disease in this population. All longitudinal based studies in the literature reporting the incidence of bone fractures or kidney stones following bariatric surgery were reviewed. Moreover, all publications over the past decade which assessed changes in bone mineral density and bone quality, or explored underlying pathophysiologic mechanisms of bone and kidney stone disease were carefully reviewed. This review provides sufficient data to support that osteoporotic fractures and kidney stone disease are associated with Roux-en-Y gastric bypass surgery. However, due to the limited data available to date, no definitive conclusion could yet be drawn whether sleeve gastrectomy or adjustable gastric banding is associated with bone fractures and kidney stones. Bariatric surgery has emerged as the most effective and sustained treatment for weight reduction. This treatment modality has been recognized to diminish the risk of cardiovascular morbidity and mortality and ameliorate diabetes mellitus complications. The derangement in mineral metabolism has emerged as a major complication following bariatric surgery. PMID- 26679438 TI - From Darkness Into Light?. PMID- 26679437 TI - Optimized Protocols for In Vitro Maturation of Rat Oocytes Dramatically Improve Their Developmental Competence to a Level Similar to That of Ovulated Oocytes. AB - The developmental capacity of in vitro-matured (IVM) oocytes is markedly lower than that of their in vivo-matured (IVO) counterparts, suggesting the need for optimization of IVM protocols in different species. There are few studies on IVM of rat oocytes, and there are even fewer attempts to improve ooplasmic maturation compared to those reported in other species. Furthermore, rat oocytes are well known to undergo spontaneous activation (SA) after leaving the oviduct; however, whether IVM rat oocytes have lower SA rates than IVO oocytes and can potentially be used for nuclear transfer is unknown. In this study, we investigated the effects of maturation protocols on cytoplasmic maturation of IVM rat oocytes and observed the possibility to reduce SA by using IVM rat oocytes. Ooplasmic maturation was assessed using multiple markers, including pre- and postimplantation development, meiotic progression, CG redistribution, redox state, and the expression of developmental potential- and apoptosis-related genes. The results showed that the best protocol consisting of modified Tissue Culture Medium-199 (TCM-199) supplemented with cysteamine/cystine and the cumulus cell monolayer dramatically improved the developmental competence of rat oocytes and supported both pre- and postimplantation development and other ooplasmic maturation makers to levels similar to that observed in ovulated oocytes. Rates of SA were significantly lower in IVM oocytes than in IVO oocytes when observed at the same intervals after nuclear maturation. In conclusion, we have optimized protocols for IVM of rat oocytes that sustain ooplasmic maturation to a level similar to ovulated oocytes. The results suggest that IVM rat oocytes might be used to reduce SA for rat cloning. PMID- 26679440 TI - Hairy Cell Leukemia and Bone Pain. AB - Hairy cell leukemia is a relatively rare but distinct B-cell lympho-proliferative disorder of the blood, bone marrow, and spleen that accounts for only 2% of all adult leukemia cases. The median age at presentation is 50-55 years, with a 4:1 male to female predominance. Although considered uncommon, a number of unusual clinical presentations have been noted in the literature, including the presence of peripheral lymphadenopathy, lytic bone lesions, skin involvement, organ involvement, and central nervous system involvement. Unlike the clinical management of other hematologic malignancies, no current system is used to stage hairy cell leukemia. PMID- 26679441 TI - Considerations for the Doctor of Nursing Practice Degree. AB - Today's progressively complex healthcare landscape increasingly demands leaders who are adept at managing change in uncertain environments. Representing this country's largest group of healthcare workers, RNs influence how research translates to practice and ensure quality patient outcomes. Doctoral programs provide prospective nursing students with opportunities to pursue degrees focused on research or practice. The doctor of nursing practice (DNP) degree emphasizes leadership in clinical settings.?. PMID- 26679442 TI - Academic Pressure and Research Ethics at the Crossroads. AB - Healthcare professionals become research scientists to improve the health and well-being of humankind. Often stemming from clinical observations, the process of writing a proposal to investigate the problem, obtaining funding, conducting the study, and disseminating findings takes considerably longer than the expectations of productivity in grant funding and publishing manuscripts for faculty on a tenure track in academia. Application back into practice, which is the goal of research, and evaluation of improving patient care and outcomes take even longer. ?. PMID- 26679443 TI - Text Messaging May Improve Abnormal Mammogram Follow-Up in Latinas. AB - PURPOSE/OBJECTIVES: To develop and pilot test a text message notification process to reduce follow-up time for women with abnormal mammograms.?. DESIGN: Formative analysis; randomized trial with delayed intervention control group.?. SETTING: Tiburcio Vasquez Health Clinic (TVHC), a federally qualified health center in Hayward, California.?. SAMPLE: 29 Spanish-speaking Latinas with abnormal mammograms.?. METHODS: A Spanish text message was developed based on findings from two focus groups and five interviews with TVHC healthcare providers. Thirteen women were assigned to receive text messages within 24 hours of receipt of abnormal mammogram by TVHC (intervention group) and 16 to receive text messages four weeks later (delayed intervention group).?. MAIN RESEARCH VARIABLES: Number of days between the abnormal mammogram and the return for follow-up appointment.?. FINDINGS: The median number of days from the abnormal mammogram report to the return for follow-up was 23 days for the intervention group and 59 days for the delayed intervention group (p = 0.0569).?. CONCLUSIONS: This study successfully developed a text message that, in Latinas, may decrease the time from receipt of an abnormal mammogram report to attendance at a follow up visit.?. IMPLICATIONS FOR NURSING: This simple, low-cost approach could result in earlier detection of breast cancers, lowering morbidity and mortality among Latinas. PMID- 26679444 TI - Psychological Functioning, Post-Traumatic Growth, and Coping in Parents and Siblings of Adolescent Cancer Survivors. AB - PURPOSE/OBJECTIVES: To examine psychological functioning, post-traumatic growth (PTG), coping, and cancer-related characteristics of adolescent cancer survivors' parents and siblings.?. DESIGN: Descriptive, correlational.?. SETTING: Children's Hospital of Western Ontario in London, Ontario, Canada.?. SAMPLE: Adolescents who finished cancer treatment 2-10 years prior (n = 31), as well as their parents (n = 30) and siblings (n = 18). ?. METHODS: Participants completed self-report measures of psychological distress, PTG, life satisfaction, coping, and cancer related characteristics.?. MAIN RESEARCH VARIABLES: Psychological functioning, PTG, and coping.?. FINDINGS: Parents' and siblings' PTG levels were similar to survivors' PTG levels; however, parents reported higher PTG than siblings. Parents who used less avoidant coping, were younger, and had higher life satisfaction experienced less psychological distress. Parents whose survivor children used more active coping reported less psychological distress. Siblings who were older used more active coping, and the longer it had been since their brother or sister was diagnosed, the less avoidant coping they used. ?. CONCLUSIONS: Childhood and adolescent cancer affects survivors' siblings and parents in unique ways.?. IMPLICATIONS FOR NURSING: Relationship to the survivor, use of coping strategies, life satisfaction, and time since diagnosis affect family members' postcancer experiences. PMID- 26679445 TI - Examining Differences in Opportunity and Eligibility for Cancer Clinical Trial Participation Based on Sociodemographic and Disease Characteristics. AB - PURPOSE/OBJECTIVES: To examine differences in opportunity and eligibility for cancer clinical trial (CCT) participation based on sociodemographic and disease characteristics.?. DESIGN: A matched cross-sectional study including a prospective oral questionnaire and retrospective electronic medical record (EMR) review.?. SETTING: A single hospital in a large academic National Cancer Institute-designated cancer center in Philadelphia, Pennsylvania.?. SAMPLE: 44 Black or Hispanic and 44 Non-Hispanic White newly diagnosed individuals matched on cancer type and age (plus or minus five years).?. METHODS: Participants answered a questionnaire to capture self-reported opportunity for CCT participation, sociodemographic information, and cancer type. With consent, the authors completed a retrospective review of the EMR to assess eligibility and collect cancer stage and performance status.?. MAIN RESEARCH VARIABLES: Opportunity and eligibility for CCT participation.?. FINDINGS: Most participants (78%) had no opportunity for participation and were ineligible for all available trials. No differences were noted in opportunity for participation or eligibility based on race or ethnicity. Participants with late-stage disease were more likely to have opportunity and be eligible for CCT participation (p = 0.001). Those with private insurance were less likely to have opportunity for participation (p = 0.05).?. CONCLUSIONS: Limited trial availability and ineligibility negatively influenced opportunity for CCT participation for all populations. Levels of under representation for CCT participation likely vary within and across sociodemographic and disease characteristics, as well as across healthcare settings.?. IMPLICATIONS FOR NURSING: The unique roles of nurse navigators and advanced practice nurses can be leveraged to increase opportunities for CCT participation for all populations. PMID- 26679446 TI - Oncology Nursing Certification: Relation to Nurses' Knowledge and Attitudes About Pain, Patient-Reported Pain Care Quality, and Pain Outcomes. AB - PURPOSE/OBJECTIVES: To (a) compare pain knowledge and attitudes between nurses with oncology certified nurse (OCN(r)) status, non-OCN(r)-certified nurses, and nurses ineligible for certification and (b) examine the relationships among OCN(r) status, nurses' knowledge and attitudes about pain, patient-reported quality of nursing pain care, and pain outcomes. ?. DESIGN: Prospective, correlational survey design. Patients were nested within nurses. ?. SETTING: Six inpatient oncology units in three hospitals. SAMPLE: 91 nurses in three states (28 OCN(r)-certified nurses, 37 noncertified nurses, and 26 not eligible for certification). Certification status was validated for 105 nurses who were matched with a sample of 320 patients. ?. METHODS: Nurses completed a survey, and matched adult patients who were experiencing pain rated their pain care quality and pain experience during the past shift. ?. MAIN RESEARCH VARIABLES: Demographic characteristics, certification status, and responses to the Nurse Knowledge and Attitudes Survey Regarding Pain (NKASRP), Pain Care Quality Survey Nursing, and modified Brief Pain Inventory (Short Form). ?. FINDINGS: OCN(r) certified nurses scored significantly higher on the NKASRP (82% correct) compared to non-OCN(r) eligible nurses (76%) and non-OCN(r) ineligible nurses (74%) (p < 0.001). Only 43% overall achieved a benchmark of 80% correct. No statistically significant relationships existed between (a) certification status and pain care quality or pain outcomes or (b) NKASRP and care quality or outcomes (p > 0.05).?. CONCLUSIONS: OCN(r)-certified nurses' knowledge and attitudes related to pain management were superior to noncertified nurses. Neither knowledge and attitudes nor OCN(r) status were associated with pain care quality or pain outcomes. ?. IMPLICATIONS FOR NURSING: Knowledge is necessary but insufficient to improve patient outcomes; providing optimal pain care requires action. Sustained efforts to improve cancer pain management are indicated. PMID- 26679447 TI - Differences in Colorectal Cancer Risk Knowledge Among Alabamians: Screening Implications. AB - PURPOSE/OBJECTIVES: To explore differences in cancer risk knowledge and colorectal cancer (CRC) knowledge among adults in Alabama. ?. RESEARCH APPROACH: Telephone interviews were conducted using an 80-item questionnaire that included 14 demographic questions and 26 general questions regarding healthcare quality, sources of health-related information, and cancer fears and risk factors. Also included were 40 questions dealing with CRC perceptions and experiences (asked only of respondents aged 50 years or older).?. SETTING: A standard random-digit dialed statewide telephone survey, targeting adult residents of Alabama. Interviews were conducted during about seven weeks in 2012. ?. PARTICIPANTS: 1,024 participants, including 615 who were aged 50 years or older. Most of the participants identified as Caucasian.?. METHODOLOGIC APPROACH: A secondary data analysis using data from a CRC screening survey of Alabama residents conducted in 2012 by the University of South Alabama polling group via telephone.?. FINDINGS: Knowledge of general cancer risk factors predicted disagreement with the statement, "There is nothing you can do to avoid getting cancer," and disagreement with the statement, "Only people with signs or symptoms should be screened for CRC." Binary logistic regression showed that those higher in CRC risk knowledge were more likely to have been screened for CRC. ?. CONCLUSIONS: Knowledge of general cancer risk factors may increase self-efficacy. In addition, individuals with increased knowledge of colorectal cancer risk factors were more likely to participate in CRC screening. ?. INTERPRETATION: Nurses play an instrumental role in addressing CRC, a preventable and treatable cancer. An opportunity exists for nurses and other healthcare providers to develop culturally appropriate educational interventions to increase knowledge related to CRC, risk factors, and screening, particularly among those who are at increased risk. This education needs to occur in clinical practice and within the community. PMID- 26679448 TI - Facilitating Shared Decision Making About Prostate Cancer Screening Among African American Men. AB - PURPOSE/OBJECTIVES: To describe the development and implementation of a prostate cancer screening intervention and risk assessment decision tool.?. DESIGN: Community health promotion with pre- and post-education knowledge questionnaires.?. SETTING: Two predominantly African American churches in different suburban communities in Southern California.?. SAMPLE: A convenience sample of 50 African American men aged from 30-75 years. ?. METHODS: A Prostate Cancer Screening Decision Aid was developed and used in conjunction with an educational intervention for African American men in two suburban communities in Southern California. The educational intervention was implemented in local African American churches. The intervention included a PowerPoint(r) presentation with a four-minute video. Men completed pre- and post-education knowledge questionnaires and a risk assessment decision tool.?. MAIN RESEARCH VARIABLES: Prostate cancer knowledge, awareness of prostate cancer personal risks and benefits of prostate cancer screening, information needed for initiating discussions with provider, and intention to participate in shared decision making with healthcare providers.?. FINDINGS: An 8% increase in knowledge was calculated when comparing pre- and post- education responses. Awareness of personal risks, having the information needed to initiate a discussion with a healthcare provider, intention to participate in shared decision making within six months, prostate cancer knowledge, and having had participated in screening increased.?. CONCLUSIONS: The intervention was successful in increasing knowledge and awareness of personal risks and providing tools to facilitate shared decision making with healthcare providers.?. IMPLICATIONS FOR NURSING: Nurses can play a meaningful role in collaborating with community lay leaders to develop and implement effective health promotion interventions for African Americans. PMID- 26679449 TI - Determinants of Physical Activity Maintenance in Breast Cancer Survivors After a Community-Based Intervention. AB - PURPOSE/OBJECTIVES: To determine whether empirically selected and social cognitive theory-based factors, including baseline characteristics and modifiable behavioral and psychosocial factors, were determinants of physical activity (PA) maintenance in breast cancer survivors (BCSs) six months after a PA intervention.?. DESIGN: Single-group longitudinal study.?. SETTING: The Breast Health Centre in Winnipeg, Manitoba, Canada.?. SAMPLE: 42 survivors with stage 0 III breast cancer who completed chemotherapy and/or radiation therapy.?. METHODS: The community-based PA intervention included six weekly education and practice sessions on home-based aerobic, resistance, balance, and flexibility exercises.?. MAIN RESEARCH VARIABLES: The dependent variable, PA maintenance, was determined based on PA level measurement at six months postintervention. The independent variables of baseline characteristics (age, stage of cancer, and chronic musculoskeletal symptoms) and modifiable behavioral and psychosocial factors (PA level, fatigue, PA self-efficacy in overcoming barriers and performing tasks) were assessed at baseline and postintervention.?. FINDINGS: Multivariate regression analyses revealed that baseline fatigue and chronic musculoskeletal symptoms were the only factors significantly associated with PA maintenance.?. CONCLUSIONS: Baseline fatigue level and chronic musculoskeletal symptoms were significant determinants of PA maintenance in breast cancer survivors who had completed a community-based PA intervention. However, other key factors were considered.?. IMPLICATIONS FOR NURSING: Prior to participation in community-based PA interventions, clinicians should take into account the effects of high baseline fatigue levels and chronic musculoskeletal symptoms on potential PA maintenance, and consider additional assessments and support for BCSs to sustain their PA behavioral change.?. PMID- 26679450 TI - Perceptions of Burnout, Its Prevention, and Its Effect on Patient Care as Described by Oncology Nurses in the Hospital Setting?. AB - PURPOSE/OBJECTIVES: To identify overall perceptions of burnout within the inpatient oncology nursing population, how they perceived that burnout affected the care they provided, and how they perceived that burnout could be decreased.?. DESIGN: A quantitative descriptive study using questionnaires to describe perceptions of burnout.?. SETTING: A university-affiliated hospital using inpatient oncology nurses from three nursing units at University of Pittsburgh Medical Center Presbyterian in Pennsylvania.?. SAMPLE: A convenience sample of 61 nurses. ?. METHODS: Two instruments were used to investigate various aspects about perceptions of burnout among inpatient oncology nurses. Nurses participated on an anonymous voluntary basis by completing these instruments. ?. MAIN RESEARCH VARIABLES: Perceived burnout, perception of how burnout affects care provided to patients, and strategies to relieve burnout.?. FINDINGS: Inpatient oncology nurses report a moderate level of perceived burnout. In addition, this nursing population perceived that this burnout had a negative impact on the care they provided. Nurses believed they experienced burnout because of increased nurse patient ratios and skipped or shortened lunches or breaks. However, they perceived that burnout could be prevented when adequate resources, collaboration, teamwork, and the support of family and friends existed. ?. CONCLUSIONS: As a result of the level of care needed by inpatients with cancer, the association between burnout experienced by nurses and how it can affect care is important to recognize. One such association identified was that a relationship existed between the nurses' interactions with patients' family, friends, or visitors and increased perceptions of burnout and depersonalization. As a result, nurses can experience increased burnout and act in a manner that lacks compassion because of emotional detachment.?. IMPLICATIONS FOR NURSING: With extremely ill inpatients with cancer, nurses need to be able to manage high levels of demands from patients and their family members to provide quality and compassionate care. Nurses reported that they experience burnout because of emotional exhaustion and depersonalization as a result of missed, shortened, or skipped breaks and lunches. This perception can affect the nurse's ability to perform physically and mentally, resulting in negative effects on nurse-patient relationships. PMID- 26679451 TI - Management of Individuals With a Mutation in the Ataxia Telangiectasia Mutated Gene. AB - Advances in genetic testing have led to the identification of multiple genes associated with a hereditary risk for developing breast and other cancers. One such gene is the ataxia telangiectasia mutated (ATM) gene, which is available on many genetic panels offered to individuals with suspected hereditary risk. Genetic testing can often lead to improved understanding and clarification of risk for developing cancer, as well as allow affected individuals to make informed choices about management, including the adoption of primary prevention strategies and more aggressive screening than typically recommended in the general population. This article provides an overview of the role of mutations in the ATM gene in developing malignancies, along with emerging research on treatment implications based on genetic testing results.?. PMID- 26679452 TI - Global Cancer Disparities and the Need for New Initiatives. AB - The field of oncology is evolving at breakneck speed. Keeping up with the latest research findings, clinical best practices, and new chemotherapy agents is challenging, even with the help of the Internet. These oncologic advances, however, are far from uniformly available, and disturbing global disparities persist. In much of the world, a diagnosis of cancer remains a death sentence, and too many patients struggle to obtain access to screening, treatment, and basic symptom management. The harsh reality is that patients' chances of dying from cancer depends largely on where they live. ?. PMID- 26679453 TI - Decision-Making Styles and Levels of Involvement Concerning Breast Reconstructive Surgery: An Israeli Study. AB - PURPOSE/OBJECTIVES: To address decision-making styles among breast cancer survivors considering breast reconstruction.?. DESIGN: A primary analysis of a cross-sectional sample among survivors who chose to have breast reconstruction to examine correlations among patient age, decision-making style, and the level of involvement of decision making.?. SETTING: Hadassah Medical Center in Jerusalem, Israel.?. SAMPLE: 70 women who had undergone breast reconstruction surgery in the past five years.?. METHODS: Participants completed decision-making style and demographic questionnaires and an assessment of their level of involvement in the decision-making process. ?. MAIN RESEARCH VARIABLES: Level of involvement in decision making, decision-making model between provider and patient, and decision making styles were examined.?. FINDINGS: No correlation was found between four main decision-making styles and patient age or the extent of patient decision making involvement and age. A statistically significant correlation was found between the level of involvement in decision making and the decision-making style of the patient.?. CONCLUSIONS: Nurses should assess patient decision-making styles to ensure maximum patient involvement in the decision-making process based on personal desires regardless of age.?. IMPLICATIONS FOR NURSING: Nurses working in breast cancer care must address the decision-making process of patients diagnosed with breast cancer, including the choice to undergo breast reconstruction after mastectomy. Nurses should understand the complex factors that influence a woman's decision-making style to best help with the decision. PMID- 26679454 TI - Cross-Cultural Communication in Oncology: Challenges and Training Interests. AB - PURPOSE/OBJECTIVES: To survey oncology nurses and oncologists about difficulties in taking care of culturally and linguistically diverse patients and about interests in cross-cultural training.?. DESIGN: Descriptive, cross-sectional.?. SETTING: Web-based survey.?. SAMPLE: 108 oncology nurses and 44 oncologists. ?. METHODS: 31-item questionnaire derived from preexisting surveys in the United States and Switzerland.?. MAIN RESEARCH VARIABLES: Self-rated difficulties in taking care of culturally and linguistically diverse patients and self-rated interests in cross-cultural training.?. FINDINGS: All respondents reported communication difficulties in encounters with culturally and linguistically diverse patients. Respondents considered the absence of written materials in other languages, absence of a shared common language with patients, and sensitive subjects (e.g., end of life, sexuality) to be particularly problematic. Respondents also expressed a high level of interest in all aspects of cross cultural training (task-oriented skills, background knowledge, reflexivity, and attitudes). Nurses perceived several difficulties related to care of migrants as more problematic than physicians did and were more interested in all aspects of cross-cultural training. ?. CONCLUSIONS: The need for cross-cultural training is high among oncology clinicians, particularly among nurses.?. IMPLICATIONS FOR NURSING: The results reported in the current study may help nurses in decision making positions and educators in introducing elements of cross-cultural education into oncology curricula for nurses. Cross-cultural training should be offered to oncology nurses. PMID- 26679455 TI - Young Adults' Perceptions of the Venturing Out Pack Program as a Tangible Cancer Support Service. AB - PURPOSE/OBJECTIVES: To explore the extent to which contents contained in a backpack called the Venturing Out Pack (Vo-Pak) assist in meeting the practical, psychosocial, and informational needs of young adults (YAs), as well as how the Vo-Pak could better meet the needs of YAs. ?. RESEARCH APPROACH: Qualitative, descriptive.?. SETTING: A university-affiliated adult hospital cancer center in Montreal, Quebec.?. PARTICIPANTS: 12 YAs treated for cancer. ?. METHODOLOGIC APPROACH: One-time, individual, semistructured interviews. Verbatim transcripts underwent thematic analysis.?. FINDINGS: Participants viewed the Vo-Pak as a welcoming, ready-to-use, timely package that met many cancer-related needs. The Vo-Pak contains three kits. CONCLUSIONS: This program adds value to efforts to enhance cancer care for YAs. Integrating participants' recommendations contributes to the overarching goal of comprehensive person-centered care to an underserved segment of the cancer population.?. INTERPRETATION: The Vo-Pak program could be optimized by re-engaging healthcare professionals in its broader dissemination. Champions may be added to optimize the successful implementation of tangible support programs. YAs seem eager to connect with peers. The Vo-Pak can be instrumental in facilitating these connections and enabling these exchanges. PMID- 26679456 TI - Testicular Cancer Awareness and Screening Practices: A Systematic Review. AB - PURPOSE/OBJECTIVES: To critically appraise empirical evidence gathered from studies that (a) explored men's knowledge, awareness, and attitudes toward testicular cancer (TC) and its screening; (b) addressed their testicular self examination (TSE) practice; and/or (c) highlighted barriers and facilitators to this practice.?. DATA SOURCES: MEDLINE(r), CINAHL(r), and EMBASE(r).?. DATA SYNTHESIS: 25 articles met the inclusion criteria. Knowledge deficits regarding TC and its screening were seen. Participants who did not perform TSE often were uninformed about this practice. The majority of men perceived TC education as a positive step toward raising awareness about this malignancy.?. CONCLUSIONS: Very few men were informed about TC and TSE. Future studies should include valid and reliable tools to assess TC knowledge and screening, address the means through which TC knowledge is delivered, explore the individual's experience with TC screening, and focus on TC awareness and screening among minority groups. ?. IMPLICATIONS FOR NURSING: Although regular screening for TC is a controversial issue, nurses should encourage young men to seek medical attention in the event of discovering scrotal abnormalities. PMID- 26679469 TI - Controversies in the management of rectal cancer. A survey of French surgeons, oncologists and radiotherapists. PMID- 26679470 TI - Validation of an oncoplastic breast simulator for assessment of technical skills in wide local excision. AB - BACKGROUND: Simulation enables safe practice and facilitates objective assessment of technical skills. However, simulation training in breast surgery is rare and assessment remains subjective. The primary aim was to evaluate the construct validity of technical skills assessments in wide local excision (WLE). METHODS: Surgeons of different grades performed a WLE of a 25-mm palpable tumour on an in house synthetic breast simulator. Procedures were videotaped (blinded), reviewed retrospectively, and independently rated against a procedure-specific global rating scale by two consultant breast surgeons. Specimen radiographs were obtained and the macroscopic distance from the 'tumour' edge to the resection margin was recorded in four cardinal directions. Expert consensus was used to construct an Oncoplastic Deviation Score (ODS), assigning points for excessively wide (more than 10 mm) and, conversely, close (less than 5 mm) macroscopic margins. RESULTS: Thirty-four surgeons (12 consultant surgeons, 12 specialty trainees and 10 core trainees) participated in the study. Video-based rating scores varied hierarchically with operator expertise (P < 0.050). Inter-rater reliability was excellent (alpha >= 0.80, P < 0.050 for all scales), and inter rater agreement was moderate (kappa = 0.132-0.361, P < 0.050 for all scales). Statistically significant differences were observed on pairwise comparisons between each grade of surgeon in scores for 'exposure', 'skin flap development', 'glandular remodelling', 'skin closure' and 'final product review' (P < 0.050). Consultants received significantly fewer ODS points than specialty trainees (P = 0.012) and core trainees (P = 0.028). Compared with experts (median 9.0 mm), wider margins were observed amongst specialty trainees (median 12.0 mm) and narrower margins amongst core trainees (median 7.1 mm) (P = 0.001). CONCLUSION: Video ratings of performance and a proposed ODS differentiate surgeons based on technical skills in WLE and may be useful for objective assessment of breast surgery trainees. PMID- 26679471 TI - Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions 1 August-30 September 2015. PMID- 26679472 TI - TLR2 Regulates Complement-Mediated Inflammation Induced by Blood Loss During Hemorrhage. AB - Hemorrhagic shock resulting from blood loss directs the majority of the blood to the vital organs, dramatically reducing blood flow to the intestines and resulting in damage and inflammation. The excessive intestinal inflammatory response includes pro-inflammatory cytokines and complement activation, although the mechanism is not clear. Toll-like receptors play a vital role in the innate immune response and toll-like receptor 2 (TLR2) is required for intestinal ischemia/reperfusion-induced injury. We hypothesized that TLR2 plays an integral role in the intestinal inflammatory response after hemorrhage and subjected C57Bl/6 wild-type and Tlr2(-/-) mice to atraumatic loss of ~30% total blood volume. Two hours after blood removal, the intestinal injury and inflammation were assessed. We demonstrate that compared with wild-type control mice, Tlr2(-/ ) mice sustain less intestinal damage and inflammation. Importantly, TLR2 regulated eicosanoid and complement activation and IL-12 and TNFalpha secretions, indicating interactions between TLR2 and complement in response to significant blood loss. PMID- 26679473 TI - From conception to evaluation of mobile services for people with head injury: A participatory design perspective. AB - Adults with cognitive impairments lack the means to organise their daily life, plan their appointments, cope with fatigue, and manage their budget. They manifest interest in using new technologies to be part of society. Unfortunately, the applications offered on smart phones are often beyond their cognitive abilities. The goal of this study was to design a mobile cognitive assistant to enhance autonomy of people living with acquired traumatic brain injury. Participatory design methodologies guided this research by involving adults with cognitive impairments (CI) and their caregivers in the early stages of the design process. The population of the study is composed of four male adults who present cognitive impairments (three with head injury and one with stroke) and three caregivers. The first phase of this research was to design the Services Assistance Mobile and Intelligent (SAMI) application based on the needs expressed by the participants. During three focus groups, needs emerged concerning planning, health monitoring and money management and led to the implementation of assistive solutions on an Android mobile phone. During the second phase, the participants evaluated the mobile assistant SAMI at home for eight weeks. The results demonstrate that the participants were able to participate actively in the conception of SAMI and to use it successfully. People with CI showed a slight improvement in their life satisfaction. Due to the small number of participants, these promising results need to be confirmed by a larger-scale study. PMID- 26679474 TI - Older adults with poor self-rated memory have less depressive symptoms and better memory performance when perceived self-efficacy is high. AB - OBJECTIVE: To investigate whether self-efficacy moderates the association between self-rated memory and depressive symptoms in a large sample of older adults. The influence of self-efficacy and depressive symptoms on memory performance was also examined in a subsample of individuals who reported poor memory. METHODS: Non demented participants (n = 3766) were selected from the 2012 wave of the Health and Retirement Study. Depressive symptomatology was assessed with the 8-item Center for Epidemiologic Studies Depression Scale. A modified version of the Midlife Developmental Inventory Questionnaire was used as the measure of self efficacy. Participants were asked to rate their memory presently on a five-point scale from Excellent (1) to Poor (5). Immediate memory and delayed memory (after a 5-min interval) were measured by the number of correct words recalled from a 10 item word list. RESULTS: Multiple regression analyses revealed that negative ratings of memory were significantly associated with greater levels of depressive symptoms, with this effect being greatest in those with low levels of self efficacy. Additionally, greater self-efficacy was associated with optimal objective memory performances but only when depressive symptoms were low in individuals who reported poor memory function (n = 1196). CONCLUSION: Self efficacy moderates the relationship between self-rated memory function and depressive symptoms. Higher self-efficacy may buffer against the impact of subjective memory difficulty on one's mood and thereby mitigating the effect of depressive symptoms on memory. Interventions should focus on increasing perceived self-efficacy in older adults reporting poor memory function to potentially minimize memory impairment. PMID- 26679475 TI - Topology-guided design of an anionic bor-network for photocatalytic [Ru(bpy)3](2+) encapsulation. AB - An anionic metal-organic framework, PCN-99, has been synthesized through a topology-guided strategy; its underlying bor-net is realized by the use of a tetrahedral [In(COO)4](-) node and a judiciously designed trigonal planar linker. In light of its anionic nature, the inherent cuboctahedral cage and 1D channel make PCN-99 an excellent matrix to encapsulate the photocatalytic [Ru(bpy)3](2+). PMID- 26679477 TI - The Morrison technique: a free-hand method for capturing photomicrographs using a smartphone. PMID- 26679476 TI - Genetic dissection of heterosis using epistatic association mapping in a partial NCII mating design. AB - Heterosis refers to the phenomenon in which an F1 hybrid exhibits enhanced growth or agronomic performance. However, previous theoretical studies on heterosis have been based on bi-parental segregating populations instead of F1 hybrids. To understand the genetic basis of heterosis, here we used a subset of F1 hybrids, named a partial North Carolina II design, to perform association mapping for dependent variables: original trait value, general combining ability (GCA), specific combining ability (SCA) and mid-parental heterosis (MPH). Our models jointly fitted all the additive, dominance and epistatic effects. The analyses resulted in several important findings: 1) Main components are additive and additive-by-additive effects for GCA and dominance-related effects for SCA and MPH, and additive-by-dominant effect for MPH was partly identified as additive effect; 2) the ranking of factors affecting heterosis was dominance > dominance by-dominance > over-dominance > complete dominance; and 3) increasing the proportion of F1 hybrids in the population could significantly increase the power to detect dominance-related effects, and slightly reduce the power to detect additive and additive-by-additive effects. Analyses of cotton and rapeseed datasets showed that more additive-by-additive QTL were detected from GCA than from trait phenotype, and fewer QTL were from MPH than from other dependent variables. PMID- 26679478 TI - Complete mitochondrial genome and phylogenetic relationship analyses of Amphioctopus aegina (Gray, 1849) (Cephalopoda: Octopodidae). AB - In this paper, the circular mitochondrial genome of Amphioctopus aegina (Cephalopoda: Octopodidae) was sequenced. The whole mitogenome of A. aegina was 15 545 base pairs (bp) in length with a base composition of 42.53% A, 33.26% T, 16.70% C, and 7.51% G. The complete mitogenome contained 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes, and a major non-coding region. The gene arrangements of A. aegina showed remarkable similarity to other Octopodidae species reported. The phylogenetic relationships were reconstructed with the concatenated sequences of the 13 PCGs of the mitochondrial genome, and illustrated that A. aegina had the closest genetic relatives to A. fangsiao. PMID- 26679479 TI - Neural Sensitivity to Smoking Stimuli Is Associated With Cigarette Craving in Adolescent Smokers. AB - PURPOSE: Adolescents initiate cigarette smoking at disproportionately high rates, despite widespread knowledge of its health-compromising and long-term consequences. Psychosocial factors clearly play a role in adolescent smoking initiation, but the role of the developing adolescent brain in this behavior remains unclear. The goal of the present study was to determine whether greater neural sensitivity to smoking cues in adolescents compared to adults underlies increased proclivity toward smoking behavior and craving. METHODS: We addressed this question in a sample of adolescent (n = 39) and adult (n = 39) smokers and nonsmokers by assessing craving in response to smoking videos that featured late adolescents/young adults while participants underwent functional magnetic resonance imaging. RESULTS: Ventral striatal activation mediated the relationship between video-induced craving and subsequent desires to smoke following the scan in adolescent smokers only. We also found that functional coupling between striatal and cortical regions was associated with increased craving in adolescent smokers. CONCLUSIONS: These novel results demonstrate that adolescent smokers may be more neurobiologically responsive to smoking stimuli than adults, perhaps because of ongoing ontogenetic changes in adolescents that normatively occur in frontostriatal circuitry. PMID- 26679480 TI - Comparison of intranasal fluticasone spray, budesonide atomizer, and budesonide respules in patients with chronic rhinosinusitis with polyposis after endoscopic sinus surgery. AB - BACKGROUND: Nasal steroids are a critical part of the management of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic sinus surgery (ESS). Increasingly, practitioners are using budesonide respules delivered to the sinonasal cavities, which is an off-label use, in lieu of traditional nasal steroids. There has been little research comparing budesonide with traditional nasal steroids and the most effective delivery method of budesonide. METHODS: A randomized controlled trial was performed on patients after ESS for CRSwNP in a tertiary care center. Patients were randomized into 1 of 3 groups: group A received fluticasone nasal spray twice daily; group B received budesonide respules via a mucosal atomization device (MAD) twice daily; and group C received budesonide respules instilled via the vertex-to-floor (VF) position twice daily. Primary endpoints were 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy scores at 6 months. RESULTS: Thirty-two patients were enrolled in the study, 23 of whom completed the 6-month trial. There were no significant differences among groups A, B, and C with respect to age, gender, asthma, aspirin sensitivity, or previous ESS. Group B had a statistically significant greater reduction in SNOT-22 and Lund-Kennedy scores at the primary endpoint of 6 months compared to groups A and C. Group C had the next greatest reduction, which was statistically significant, followed by group A. CONCLUSION: Patients treated with budesonide after ESS for CRSwNP had greater improvement in SNOT-22 and Lund-Kennedy scores compared to fluticasone at 6 months. The data supports the use of budesonide respules, particularly with a MAD, over fluticasone for CRSwNP patients after ESS. PMID- 26679481 TI - [Comparison of Open vs. Laparoscopic Techniques in Complete Mesocolic Excision (CME) During Right Hemicolectomy]. AB - AIMS: The technique of open complete mesocolic excision (CME) has improved the outcomes of patients with colon carcinoma. Meanwhile it has become an established international standard procedure. It remains unclear if laparoscopic procedures are able to match the high quality of open resections. A video comparison of the two methods gives insight into the different dissection techniques. INDICATION: Open CME is demonstrated in a 79-year-old female patient with an asymptomatic carcinoma of the ascending colon verified by histopathology. The tumour was diagnosed during routine colonoscopy. No distant metastases were identified during the staging procedure. Laparoscopic CME is performed in a 72-year-old female patient with a biopsy-proven carcinoma of the ascending colon. Similarly this patient was diagnosed during a screening colonoscopy and had no distant metastasis. METHODS: During open CME the ascending colon and the duodenum are mobilised by sharp dissection between the parietal and visceral layer of the mesentery. Afterwards the ascending and transverse mesocolon are dissected from the duodenum and pancreas. The parietal and the visceral mesentery are strictly preserved during these procedures. After the exposure of the superior mesenteric artery and vein, a central dissection of the vessels follows. The colon is cut 10 cm distal to the carcinoma. An ileotransversostomy is performed with a running suture. The hole in the mesentery is closed. The laparoscopic CME is performed using the 4-trocar technique with an umbilical camera position following a medial to lateral approach with primary dissection of the superior mesenteric vein. Radicular vessel ligation opens the space dorsal to the mesocolon with the border lamella remaining intact. The space is widened until the ascending colon is entirely mobilised. The mobilised colon is eventrated through an enlarged umbilical midline incision. Colon resection and the subsequent two-layered side to-side ileotransversostomy are performed in a standard open surgical fashion. CONCLUSION: Open and laparoscopic CME enable central vessel dissection while preserving the mesenteric layers. However, the laparoscopic procedure is technically demanding and should therefore only be performed by surgeons experienced in laparoscopy. PMID- 26679482 TI - [In Process Citation]. PMID- 26679483 TI - Examining the Influence of Measures of Adiposity on Cognitive Function in Middle Age and Older African Americans. AB - The objectives of the study were to examine whether measures of total obesity (body mass index [BMI]) and central obesity (waist circumference [WC] and waist to-hip ratio [WHR]) are associated with cognitive function in African Americans, and whether sex moderates these associations. A sample of 194 African Americans, with a mean age of 58.97 years, completed a battery of cognitive tests and a self reported health questionnaire. Height, weight, waist and hip circumference, and blood pressure were assessed. Linear regression analyses were run. Results suggested lower performance on measures of verbal fluency and complex attention/cognitive flexibility was accounted for by higher levels of central adiposity. Among men, higher WHR was more strongly related to complex attention/cognitive flexibility performance, but for women, WC was a salient predictor. Higher BMI was associated with poorer verbal memory performance among men, but poorer nonverbal memory performance among women. Findings suggest a need for healthy lifestyle interventions for African Americans to maintain healthy weight and cognitive function. PMID- 26679484 TI - Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis. AB - Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium. PMID- 26679485 TI - Contribution of arginase to manganese metabolism of Aspergillus niger. AB - Aspects of manganese metabolism during normal and acidogenic growth of Aspergillus niger were explored. Arginase from this fungus was a Mn[II]-enzyme. The contribution of the arginase protein towards A. niger manganese metabolism was investigated using arginase knockout (D-42) and arginase over-expressing (DeltaXCA-29) strains of A. niger NCIM 565. The Mn[II] contents of various mycelial fractions were found in the order: D-42 strain < parent strain < DeltaXCA-29 strain. While the soluble fraction forms 60% of the total mycelial Mn[II] content, arginase accounted for a significant fraction of this soluble Mn[II] pool. Changes in the arginase levels affected the absolute mycelial Mn[II] content but not its distribution in the various mycelial fractions. The A. niger mycelia harvested from acidogenic growth media contain substantially less Mn[II] as compared to those from normal growth media. Nevertheless, acidogenic mycelia harbor considerable Mn[II] levels and a functional arginase. Altered levels of mycelial arginase protein did not significantly influence citric acid production. The relevance of arginase to cellular Mn[II] pool and homeostasis was evaluated and the results suggest that arginase regulation could occur via manganese availability. PMID- 26679486 TI - Empirical evidence about inconsistency among studies in a pair-wise meta analysis. AB - This paper investigates how inconsistency (as measured by the I2 statistic) among studies in a meta-analysis may differ, according to the type of outcome data and effect measure. We used hierarchical models to analyse data from 3873 binary, 5132 continuous and 880 mixed outcome meta-analyses within the Cochrane Database of Systematic Reviews. Predictive distributions for inconsistency expected in future meta-analyses were obtained, which can inform priors for between-study variance. Inconsistency estimates were highest on average for binary outcome meta analyses of risk differences and continuous outcome meta-analyses. For a planned binary outcome meta-analysis in a general research setting, the predictive distribution for inconsistency among log odds ratios had median 22% and 95% CI: 12% to 39%. For a continuous outcome meta-analysis, the predictive distribution for inconsistency among standardized mean differences had median 40% and 95% CI: 15% to 73%. Levels of inconsistency were similar for binary data measured by log odds ratios and log relative risks. Fitted distributions for inconsistency expected in continuous outcome meta-analyses using mean differences were almost identical to those using standardized mean differences. The empirical evidence on inconsistency gives guidance on which outcome measures are most likely to be consistent in particular circumstances and facilitates Bayesian meta-analysis with an informative prior for heterogeneity. (c) 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. (c) 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. PMID- 26679487 TI - Persistence of Clostridium difficile RT 237 infection in a Western Australian piggery. AB - Clostridium difficile is commonly associated with healthcare-related infections in humans, and is an emerging pathogen in food animal species. There is potential for transmission of C. difficile from animals or animal products to humans. This study aimed to determine if C. difficile RT 237 had persisted in a Western Australian piggery or if there had been a temporal change in C. difficile diversity. C. difficile carriage in litters with and without diarrhea was investigated, as was the acquisition of C. difficile over time using cohort surveys. Rectal swabs were obtained from piglets aged 1-10 days to determine prevalence of C. difficile carriage and samples were obtained from 20 piglets on days 1, 7, 13, 20, and 42 of life to determine duration of shedding. Isolation of C. difficile from feces was achieved by selective enrichment culture. All isolates were characterized by standard molecular typing. Antimicrobial susceptibility testing was performed on selected isolates (n = 29). Diarrheic piglets were more likely to shed C. difficile than the non-diseased (p = 0.0124, chi2). In the cohort study, C. difficile was isolated from 40% samples on day 1, 50% on day 7, 20% on day 13, and 0% on days 20 and 42. All isolates were RT 237 and no antimicrobial resistance was detected. The decline of shedding of C. difficile to zero has public health implications because slaughter age pigs have a low likelihood of spreading C. difficile to consumers via pig meat. PMID- 26679488 TI - Averrhoa carambola L. peel extract suppresses adipocyte differentiation in 3T3-L1 cells. AB - Obesity is associated with an increased risk of many chronic diseases. Recently, a growing body of evidence has shown that phytochemicals may inhibit adipogenesis and obesity. In this study, we report for the first time, the ability of Averrhoa carambola L. peel extract commonly known as star fruit (SFP) to effectively suppress adipocyte differentiation in 3T3-L1 preadipocytes and therefore, address it as a potential candidate to treat obesity and its related diseases. (-) Epicatechin was identified as a bioactive compound likely responsible for this suppression. As the genetic expression studies revealed that the adipogenic activity of SFP extract was due to the simultaneous downregulation of the C/EBPalpha and PPARgamma as well as the upregulation of PPARalpha receptor genes, a detailed computational docking study was also elucidated to reveal the likely binding mode of (-)-epicatechin to the receptor of interest, accounting for the likely mechanism that results in the overall suppression of adipocyte differentiation. PMID- 26679489 TI - Association Between Student Purchases of Beverages During the School Commute and In-School Consumption of Sugar-Sweetened Beverages, San Francisco Bay Area, 2013. AB - INTRODUCTION: Consumption of sugar-sweetened beverages (SSBs) such as sodas, fruit-flavored drinks, and sports drinks is a major contributor to childhood obesity. One strategy to reduce children's SSB consumption has been to restrict the sale of SSBs in schools. However, such policies may not sufficiently curb students' SSB intake, because students can obtain SSBs elsewhere, including from stores located on their school commute. Little is known about students' purchases of beverages during the school commute or about whether this purchasing behavior is related to in-school SSB consumption. The objective of this study was to describe where students from low-income, ethnically diverse communities obtain the SSBs they drink during school lunchtime and to examine whether students who purchase beverages while traveling to and from school are more likely to drink SSBs during school lunchtime. METHODS: We analyzed survey data from a random sample of low-income, ethnically diverse middle school students (N = 597) who participated in a randomized controlled trial of a water promotion intervention. We used logistic regression analysis to examine the association between students' purchase of beverages during the school commute and their SSB consumption during school lunchtime. RESULTS: One-fifth (20.4%) of students drank an SSB during lunch. Approximately 23% of SSBs were obtained during the school commute. Students who reported buying beverages during their school commute (50.1% of all students) were more likely to report drinking SSBs during lunch than students who reported that they do not buy beverages during the school commute (adjusted odds ratio 3.32, 95% confidence interval, 2.19-5.05, P < .001). CONCLUSION: Students' purchase of beverages during the school commute was strongly associated with SSB consumption during school lunchtime. Interventions could benefit from focusing on retail environments (e.g., encouraging retailers to promote healthy beverages, posting beverage calorie information). PMID- 26679490 TI - Investigating Measures of Social Context on 2 Population-Based Health Surveys, Hawaii, 2010-2012. AB - Measures from the Social Context Module of the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System were used on 2 population based health surveys in Hawaii to explicate the role of the nonmedical and social determinants of health; these measures were also compared with conventional socioeconomic status (SES) variables. Results showed that the self-reported SES vulnerabilities of food and housing insecurity are both linked to demographic factors and physical and mental health status and significant when controlling for the conventional measures of SES. The social context module indicators should be increasingly used so results can inform appropriate interventions for vulnerable populations. PMID- 26679491 TI - Patterns of Chronic Conditions and Their Associations With Behaviors and Quality of Life, 2010. AB - INTRODUCTION: Co-occurring chronic health conditions elevate the risk of poor health outcomes such as death and disability, are associated with poor quality of life, and magnify the complexities of self-management, care coordination, and treatment planning. This study assessed patterns of both singular and multiple chronic conditions, behavioral risk factors, and quality of life in a population based sample. METHODS: In a national survey, adults (n = 4,184) answered questions about the presence of 27 chronic conditions. We used latent class analysis to identify patterns of chronic conditions and to explore associations of latent class membership with sociodemographic characteristics, behavioral risk factors, and health. RESULTS: Latent class analyses indicated 4 morbidity profiles: a healthy class (class 1), a class with predominantly physical health conditions (class 2), a class with predominantly mental health conditions (class 3), and a class with both physical and mental health conditions (class 4). Class 4 respondents reported significantly worse physical health and well-being and more days of activity limitation than those in the other latent classes. Class 4 respondents were also more likely to be obese and sedentary, and those with predominantly mental health conditions were most likely to be current smokers. CONCLUSIONS: Subgroups with distinct patterns of chronic conditions can provide direction for screening and surveillance, guideline development, and the delivery of complex care services. PMID- 26679492 TI - Promoting Employee Health Through an American Cancer Society Program, The CEOs Challenge, Washington State, 2013-2015. AB - INTRODUCTION: Evidence-based practices in the workplace can increase levels of healthy eating, cancer screening, physical activity, and tobacco cessation but are underused, even in large workplaces. This report summarizes an evaluation of the first year of The CEOs Challenge, a program developed by the American Cancer Society to promote implementation and maintenance of health-promoting, evidence based workplace practices by large companies. METHODS: Use of 17 evidence-based practices by 17 companies in the Washington State Chapter of the American Cancer Society's CEOs Against Cancer network was assessed via survey and scored from 0 to 100. Companies received a written report of their baseline performance, followed by at least quarterly consultations with American Cancer Society staff members trained to assist in implementation of these practices. Follow-up performance was measured at 1 year. RESULTS: At baseline, implementation scores were 54.8 for cancer screening, 46.5 for healthy eating, 59.8 for physical activity, and 68.2 for tobacco cessation. At follow-up, scores increased by 19.6 for cancer screening, 19.4 for healthy eating, 16.0 for physical activity, and 9.4 points for tobacco cessation. CONCLUSION: The CEOs Challenge is a promising approach to chronic disease prevention via the workplace. It brings together one of the nation's largest health-promoting voluntary agencies with the nation's largest employers to promote evidence-based practices targeted at the most common causes of disease and death. The program increased the adoption of these practices and was well-accepted. PMID- 26679493 TI - Hamilton's rule, inclusive fitness maximization, and the goal of individual behaviour in symmetric two-player games. AB - Hamilton's original work on inclusive fitness theory assumed additivity of costs and benefits. Recently, it has been argued that an exact version of Hamilton's rule for the spread of a pro-social allele (rb > c) holds under nonadditive pay offs, so long as the cost and benefit terms are defined as partial regression coefficients rather than pay-off parameters. This article examines whether one of the key components of Hamilton's original theory can be preserved when the rule is generalized to the nonadditive case in this way, namely that evolved organisms will behave as if trying to maximize their inclusive fitness in social encounters. PMID- 26679494 TI - [The Berlin diagnostic algorithm for painful knee TKA]. AB - BACKGROUND: Approximately 20% of patients are unsatisfied with their postoperative results after total knee arthroplasty (TKA). Main causes for revision surgery are periprosthetic infection, aseptic loosing, instability and malalignment. In rare cases secondary progression of osteoarthritis of the patella, periprosthetic fractures, extensor mechanism insufficiency, polyethylene wear and arthrofibrosis can cause the necessity for a reintervention. Identifying the reason for a painful knee arthroplasty can be very difficult, but is a prerequisite for a successful therapy. AIM: The aim of this article is to provide an efficient analysis of the painful TKA by using a reproducible algorithm. DISCUSSION: Basic building blocks are the medical history with the core issues of pain character and the time curve of pain concerning surgery. This is followed by the basic diagnostics, including clinical, radiological, and infectiological investigations. Unique failures like periprosthetic infection or aseptic loosening can thereby be diagnosed in the majority of cases. If the cause of pain is not clearly attributable using the basic diagnostics tool, further infectiological investigation or diagnostic imaging are necessary. If the findings are inconsistent, uncommon causes of symptoms, such as extra-articular pathologies, causalgia or arthrofibrosis, have to be considered. In cases of ongoing unexplained pain, a revision is not indicated. These patients should be re-evaluated after a period of time. PMID- 26679495 TI - Facility-based delivery in the context of Zimbabwe's HIV epidemic--missed opportunities for improving engagement with care: a community-based serosurvey. AB - BACKGROUND: In developing countries, facility-based delivery is recommended for maternal and neonatal health, and for prevention of mother-to-child HIV transmission (PMTCT). However, little is known about whether or not learning one's HIV status affects one's decision to deliver in a health facility. We examined this association in Zimbabwe. METHODS: We analyzed data from a 2012 cross-sectional community-based serosurvey conducted to evaluate Zimbabwe's accelerated national PMTCT program. Eligible women (>=16 years old and mothers of infants born 9-18 months before the survey) were randomly sampled from the catchment areas of 157 health facilities in five of ten provinces. Participants were interviewed about where they delivered and provided blood samples for HIV testing. RESULTS: Overall 8796 (77 %) mothers reported facility-based delivery; uptake varied by community (30-100%). The likelihood of facility-based delivery was not associated with maternal HIV status. Women who self-reported being HIV positive before delivery were as likely to deliver in a health facility as women who were HIV-negative, irrespective of when they learned their status - before (adjusted prevalence ratio (PRa) = 1.04, 95% confidence interval (CI) = 1.00 1.09) or during pregnancy (PRa = 1.05, 95% CI = 1.01-1.09). Mothers who had not accessed antenatal care or tested for HIV were most likely to deliver outside a health facility (69%). Overall, however 77% of home deliveries occurred among women who had accessed antenatal care and were HIV-tested. CONCLUSIONS: Uptake of facility-based delivery was similar among HIV-infected and HIV-uninfected mothers, which was somewhat unexpected given the substantial technical and financial investment aimed at retaining HIV-positive women in care in Zimbabwe. PMID- 26679496 TI - Challenge to pediatric anatomical variation : Can we draw the ideal line on the pediatric I-gel? AB - OBJECTIVE: I-gel is a noncuff type of laryngeal airway mask. No horizontal line has yet been determined as an ideal position for pediatric sizes because of the variability in length of the oropharyngeal-laryngeal arch in children. We investigated whether there is a correlation between insertion length and patient body weight or height for the pediatric I-gel sizes from 1.5 to 2.5. METHODS: With parental informed consent, we planned to maintain the airway of 130 children aged from 7 months to 13 years by using the I-gel device under general anesthesia. The following two parameters were evaluated: (1) distance between the teeth and the connector wing; (2) insertion length (distance from the distal end of the gastric tube to the teeth). Size selection was determined on the basis of patients' body weight. We identified the relationship between each parameter and height or weight. RESULTS: Average insertion length became gradually longer with increasing height and weight. Spearman's R between insertion length and height or weight was 0.8. There was more correlation with height than with weight in pediatric size 2.5. CONCLUSION: Results suggested that it is possible to draw an ideal line on the I-gel with sizes 1.5 and 2 only. PMID- 26679498 TI - Trends in the use of gastrostomies at a tertiary paediatric referral centre. AB - OBJECTIVES: The aims of this study were to describe the population of paediatric patients undergoing gastrostomy placement at a Norwegian tertiary referral centre and to investigate trends over time in patient characteristics and operative technique. MATERIALS AND METHODS: Patients <15 years of age getting a primary gastrostomy from 1994 to 2012 were included in this retrospective observational study. Patient data were collected from medical records and the National Registry. RESULTS: Six-hundred forty-nine patients with a median age of 1.2 years [gestational week 30-14.9 years] were included. Neurological disorders (ND) was the most common underlying group of diagnosis (n = 311, 48%), followed by cardiac disease 104 (16%), congenital anomalies 85 (13%), respiratory disease 43 (7%), malignancy 29 (5%), and others 77 (12%). At follow-up, 162 (25%) patients were dead. A percutaneous endoscopic technique (PEG) was used in 401 (62%) patients, open surgery (OPEN) in 201 (31%) and laparoscopy (LAP) in 47 (7%). The number of gastrostomies per year more than doubled during the period (p < 0.001). More patients with cardiac disease and congenital anomalies were given a gastrostomy during the last years (all p < 0.05), whereas the number of patients with ND remained stable. Furthermore, there has been a decrease in median age and an increase in the number of PEG and LAP (p < 0.05). CONCLUSION: The number of gastrostomy insertions has increased from 1994 to 2012. NDs is the most common underlying diagnosis in patients receiving a gastrostomy, PEG is the most common technique and patient characteristics have changed during the study period. PMID- 26679497 TI - Review of crisis resource management (CRM) principles in the setting of intraoperative malignant hyperthermia. AB - The practice of medicine is characterized by routine and typical cases whose management usually goes according to plan. However, the occasional case does arise which involves rare catastrophic emergencies, such as intraoperative malignant hyperthermia (MH), which require a comprehensive, coordinated, and resource-intensive treatment plan. Physicians are expected to provide expert quality care for routine, typical cases, but is it reasonable to expect the same standard of expertise and comprehensive management when the emergency involves a rare entity? Although physicians would like to say yes to this question, the reality is that no physician will ever amass the amount of experience in patient care needed to truly qualify as an expert in the management of a rare emergency entity, such as MH. However, physicians can become expert in the global process of managing emergencies by using the principles of crisis resource management (CRM). In this article, we review the key concepts of CRM, using a real life example of a team who utilized CRM principles to successfully manage an intraoperative MH crisis, despite there being no one on the team who had ever previously encountered a true MH crisis. PMID- 26679500 TI - [Ophthalmological assessment in procedures for disability benefits for the blind : Why medical certificates alone are insufficient]. AB - BACKGROUND AND OBJECTIVES: Financial aid for the blind which is awarded based only on medical certificates and results of examinations has in the past resulted in too many false diagnoses; therefore, Bavaria seeks to pay financial aid to the blind only on the basis of a specific ophthalmological assessment according to the standards of the German pension medical ordinance (VersMedV, Versorgungsmedizinische Verordnung). Because these ophthalmological assessments initially contribute to a higher financial burden on the state, longer processing times and inconvenience to the patient, investigations should be undertaken to determine if ophthalmological findings, reports and medical certificates can be a suitable basis for an expert assessment and in how many cases blindness which had been certified by the original examination could be confirmed by a specific ophthalmological assessment. METHODS: A total of 925 applications for financial assistance to the blind within the catchment area of the Bavarian Center for Family and Social Services (ZBFS, Zentrum Bayern Familie und Soziales) regional center in Upper Bavaria between 2003 and 2008, all of which had been subjected to an assessment by the same practitioner acting as external expert, were statistically analyzed. RESULTS: Of the 357 applicants who had been classified as blind according to the medical certificate and findings, 283 (79 %) were confirmed as being blind after the assessment and in 73 (21 %) blindness could not be confirmed. Of the 262 applicants who were classified as not being blind during the first examination, the diagnosis was confirmed in 192 (73 %) while 70 cases (27 %) were classified as blind. Of the 304 applicants for whom an assessment was not possible by the medical certification, 165 were ultimately classified as blind and 139 as not blind. Out of 32 applicants who were explicitly classified as being blind in the medical certificate, 13 were confirmed as being blind while the remaining 18 were classified in the subsequent assessment as not blind. CONCLUSION: Apart from unambiguous cases, the awarding of financial aid to the blind should only be based on an ophthalmological assessment which follows the VersMedV guidelines. Only this approach can result in an equal treatment of all applicants before the law and the awarding of financial aid to the blind to assist those truly in need. In addition, fiscal budget results revealed that the falsely awarded financial aid to the blind reached well beyond millions of Euros. PMID- 26679499 TI - A Novel Tool Improves Existing Estimates of Recent Tuberculosis Transmission in Settings of Sparse Data Collection. AB - In any setting, a proportion of incident active tuberculosis (TB) reflects recent transmission ("recent transmission proportion"), whereas the remainder represents reactivation. Appropriately estimating the recent transmission proportion has important implications for local TB control, but existing approaches have known biases, especially where data are incomplete. We constructed a stochastic individual-based model of a TB epidemic and designed a set of simulations (derivation set) to develop two regression-based tools for estimating the recent transmission proportion from five inputs: underlying TB incidence, sampling coverage, study duration, clustered proportion of observed cases, and proportion of observed clusters in the sample. We tested these tools on a set of unrelated simulations (validation set), and compared their performance against that of the traditional 'n-1' approach. In the validation set, the regression tools reduced the absolute estimation bias (difference between estimated and true recent transmission proportion) in the 'n-1' technique by a median [interquartile range] of 60% [9%, 82%] and 69% [30%, 87%]. The bias in the 'n-1' model was highly sensitive to underlying levels of study coverage and duration, and substantially underestimated the recent transmission proportion in settings of incomplete data coverage. By contrast, the regression models' performance was more consistent across different epidemiological settings and study characteristics. We provide one of these regression models as a user-friendly, web-based tool. Novel tools can improve our ability to estimate the recent TB transmission proportion from data that are observable (or estimable) by public health practitioners with limited available molecular data. PMID- 26679501 TI - [New perspectives in retinal imaging with OCT angiography]. PMID- 26679502 TI - Increased toxin expression in a Clostridium difficile mfd mutant. AB - BACKGROUND: The symptoms of Clostridium difficile infection are mediated primarily by two toxins, TcdA and TcdB, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. Several global regulators have been implicated in the regulation of toxin expression, such as CcpA and CodY. RESULTS: During attempts to insertionally inactivate a putative secondary cell wall polysaccharide synthesis gene, we obtained several mutants containing off-target insertions. One mutant displayed an unusual branched colony morphology and was investigated further. Marker recovery revealed an insertion in mfd, a gene encoding a transcription-coupled repair factor. The mfd mutant exhibited pleiotropic effects, in particular increased expression of both toxin A and B (TcdA and TcdB) compared to the parental strain. Western blotting and cellular cytotoxicity assays revealed increased expression across all time points over a 24 h period, with inactivation of mfd resulting in at least a 10 fold increase in cell cytotoxicity. qRT-PCR demonstrated the upregulation of both toxins occurred on a transcriptional level. All effects of the mfd mutation were complemented by a plasmid-encoded copy of mfd, showing the effects are not due to polar effects of the intron insertion or to second site mutations. CONCLUSIONS: This study adds Mfd to the repertoire of factors involved in regulation of toxin expression in Clostridium difficile. Mfd is known to remove RNA polymerase molecules from transcriptional sites where it has stalled due to repressor action, preventing transcriptional read through. The consistently high levels of toxin in the C. difficile mfd mutant indicate this process is inefficient leading to transcriptional de-repression. PMID- 26679503 TI - Gender and grade differences in objectively measured physical activity and sedentary behavior patterns among Japanese children and adolescents: a cross sectional study. AB - BACKGROUND: Physical activity levels in childhood have decreased, making the promotion of children's physical activity an important issue. The present study examined gender and grade differences in objectively measured sedentary behavior, physical activity, and physical activity guideline attainment among Japanese children and adolescents. METHODS: In total, 329 boys and 362 girls age 3-15 years completed the survey. School grade, gender, height, and weight were collected by questionnaires and physical activity objectively measured using an accelerometer (Lifecorder Suzuken Co.). Physical activity level (in MET) was classified as sedentary (<1.5), light (>=1.5 to <3), moderate (>=3 to <6), or vigorous (>=6). Continuous zero accelerometer counts for >=20 min were censored and a valid accelerometry study required at least 3 days (2 weekdays and 1 weekend day) with > 600 min/day total wear time. Two-way analysis of covariance and logistic regression analyses, adjusted for weight status and accelerometer wear time, were used to examine gender and grade differences in physical activity variables and the likelihood of physical activity guideline attainment by gender and grade level. RESULTS: Participants were sedentary 441.4 (SD, 140.1) min/day or 53.7 % of the average daily accelerometer wear time of 811.2 (118.7) min, engaged in light physical activity 307.1 (70.0) min or 38.4 % of wear time, moderate physical activity 34.6 (14.8) min (4.3 %), vigorous physical activity 28.3 (19.1) min (3.6 %), and took 12462.6 (4452.5) steps/day. Boys were more physically active and took more steps/day than girls. Students in higher grades were less active than those in lower grades. Boys were significantly more likely to meet physical activity guidelines than girls (OR: 2.07, 95 % CI: 1.45-2.96). Preschoolers (6.66, 4.01-11.06), lower-grade elementary school students (17.11, 8.80-33.27), and higher-grade elementary school students (7.49, 4.71-11.92) were more likely to meet guidelines than junior high school students. CONCLUSIONS: Boys and lower-grade students engaged in more physical activity and were more likely to attain guidelines than girls and higher-grade students. These findings highlight the need for effective and sustainable strategies to promote physical activity in Japanese school children. PMID- 26679504 TI - Youth's Awareness of and Reactions to The Real Cost National Tobacco Public Education Campaign. AB - In 2014, the Food and Drug Administration (FDA) launched its first tobacco focused public education campaign, The Real Cost, aimed at reducing tobacco use among 12- to 17-year-olds in the United States. This study describes The Real Cost message strategy, implementation, and initial evaluation findings. The campaign was designed to encourage youth who had never smoked but are susceptible to trying cigarettes (susceptible nonsmokers) and youth who have previously experimented with smoking (experimenters) to reassess what they know about the "costs" of tobacco use to their body and mind. The Real Cost aired on national television, online, radio, and other media channels, resulting in high awareness levels. Overall, 89.0% of U.S. youth were aware of at least one advertisement 6 to 8 months after campaign launch, and high levels of awareness were attained within the campaign's two targeted audiences: susceptible nonsmokers (90.5%) and experimenters (94.6%). Most youth consider The Real Cost advertising to be effective, based on assessments of ad perceived effectiveness (mean = 4.0 on a scale from 1.0 to 5.0). High levels of awareness and positive ad reactions are requisite proximal indicators of health behavioral change. Additional research is being conducted to assess whether potential shifts in population-level cognitions and/or behaviors are attributable to this campaign. Current findings demonstrate that The Real Cost has attained high levels of ad awareness which is a critical first step in achieving positive changes in tobacco-related attitudes and behaviors. These data can also be used to inform ongoing message and media strategies for The Real Cost and other U.S. youth tobacco prevention campaigns. PMID- 26679506 TI - Through a Culturally Competent Lens: Why the Program Evaluation Standards Matter. AB - Program evaluation is an important tool for all health professionals as it enables us to learn what works, what does not, and how we can make improvements. In this article, we describe how both program staff and evaluators can use the program evaluation standards to ensure their work is culturally competent and stakeholder driven. When public health programs and their evaluations are responsive to culture and context, and they include meaningful-not token stakeholder engagement, we produce better evaluations that are more likely to yield useful findings and lead to more effective programs. Effective programs are culturally competent programs that benefit communities in meaningful, respectful ways. PMID- 26679505 TI - Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups. AB - A substantial burden is placed on family caregivers of patients diagnosed with brain cancers. Despite this, the support needs of the caregivers are often under recognised and not addressed adequately in current routine and patient centred clinical care. The Carer Support Needs Assessment Tool (CSNAT) is a validated instrument designed to systematically identify and address caregiver needs [corrected]. It has been trialled in an Australian palliative care community setting using a stepped wedge cluster design involving 322 family carers of terminally ill patients. The current article reports on a subset from this trial, 29 caregivers of patients with primary brain cancer, and compares their profile and outcomes to those of other cancer groups. Caregiver strain was assessed using the Family Appraisal of Caregiving Questionnaire, caregiver physical and mental wellbeing using SF12 and caregiver workload using a questionnaire on support with activities of daily living (ADL). In comparison to caregivers of patients with all other cancers, the primary brain cancer group had significantly higher levels of caregiver strain, lower levels of mental wellbeing and a higher level of ADL workload. Their physical wellness also deteriorated significantly over time. An action plan approach led to practical solutions for addressing highlighted concerns. Four themes evolved from the family caregivers' feedback interviews: The extremely challenging caregiver experience with brain cancer; the systematic and practical approach of the CSNAT during rapid changes; connection with health professionals, feeling acknowledged and empowered; and timely advice and assurance of support during the caregiving journey. This preliminary study has demonstrated that the CSNAT provides a practical and useful tool for assessing the support needs of family caregivers of patients with brain cancer and has provided the basis for a larger scale, longitudinal study that allows a more detailed characterisation of the evolving caregiver needs at different stages of the disease. PMID- 26679507 TI - Student Partnerships to Build Organizational Capacity. AB - Public health organizations-whether community-based nonprofits, centers affiliated with a university, or some other entity-can benefit greatly from partnering with students to build capacity and grow in a variety of ways. However, there are many issues to consider before taking on students as interns or volunteers. These include realistic considerations of supervisory time and effort, determining if you can actually match student skills with organizational programming not to mention legal requirements based on federal and state laws. This article provides a detailed overview of steps that organizations interested in partnering with students should follow once determining that taking on a student or multiple students is viable. These include issues around time lines, scheduling, the student selection process, supervising, ongoing mentoring, as well as expectations after the practicum or volunteer experience has ended. PMID- 26679508 TI - ArtiFacts: The Case of Jules Pedoux. PMID- 26679509 TI - Nursing's opportunity within the global refugee crisis. PMID- 26679510 TI - Interfacial Degradation of Planar Lead Halide Perovskite Solar Cells. AB - The stability of perovskite solar cells is one of the major challenges for this technology to reach commercialization, with water believed to be the major degradation source. In this work, a range of devices containing different cathode metal contacts in the configuration ITO/PEDOT:PSS/MAPbI3/PCBM/Metal are fully electrically characterized before and after degradation caused by steady illumination during 4 h that induces a dramatic reduction in power conversion efficiency from values of 12 to 1.8%. We show that a decrease in performance and generation of the S-shape is associated with chemical degradation of the metal contact. Alternatively, use of Cr2O3/Cr as the contact enhances the stability, but modification of the energetic profile during steady illumination takes place, significantly reducing the performance. Several techniques including capacitance voltage, X-ray diffraction, and optical absorption results suggest that the properties of the bulk perovskite layer are little affected in the device degradation process. Capacitance-voltage and impedance spectroscopy results show that the electrical properties of the cathode contact are being modified by generation of a dipole at the cathode that causes a large shift of the flat-band potential that modifies the interfacial energy barrier and impedes efficient extraction of electrons. Ionic movement in the perovskite layer changes the energy profile close to the contacts, modifying the energy level stabilization at the cathode. These results provide insights into the degradation mechanisms of perovskite solar cells and highlight the importance to further study the use of protecting layers to avoid the chemical reactivity of the perovskite with the external contacts. PMID- 26679511 TI - Morphological Description and Molecular Phylogeny of Two Species of Levicoleps (Ciliophora, Prostomatida), L. taehwae nov. spec. and L. biwae jejuensis nov. subspec., collected in Korea. AB - Two colepid ciliates, Levicoleps taehwae nov. spec. and L. biwae jejuensis nov. subspec., were collected from the brackish water of the Taehwa River and a small freshwater pond in Jeju Island, South Korea, respectively. Their living morphology, infraciliature, and small subunit (SSU) rRNA gene sequences were determined using standard methods. Barrel-shaped L. taehwae nov. spec. is a small ciliate with an average size of 45 * 25 MUm in vivo, about 15 ciliary rows each composed of 12 monokinetids and two perioral dikinetids, and two 20 MUm-long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,669 bp, 44.5%. This novel species is similar in body size to Coleps hirtus, and has six armor tiers and hirtus-type tier plates, and the same number of ciliary rows as C. hirtus; however, it can be distinguished from the latter by the absence of armor spines and its sequence similarity of SSU rRNA gene is about 92.8% which indicates that it is a distinct form. Levicoleps biwae jejuensis nov. subspec., is a medium colepid ciliate which has a barrel-shaped body, about 22 somatic kineties and 16 transverse ciliary rows, three mini adoral organelles, and four 15 MUm-long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,666 bp and 44.4%. PMID- 26679512 TI - BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity. AB - Mapping surface hydrophobic interactions in proteins is key to understanding molecular recognition, biological functions, and is central to many protein misfolding diseases. Herein, we report synthesis and application of new BODIPY based hydrophobic sensors (HPsensors) that are stable and highly fluorescent for pH values ranging from 7.0 to 9.0. Surface hydrophobic measurements of proteins (BSA, apomyoglobin, and myoglobin) by these HPsensors display much stronger signal compared to 8-anilino-1-naphthalene sulfonic acid (ANS), a commonly used hydrophobic probe; HPsensors show a 10- to 60-fold increase in signal strength for the BSA protein with affinity in the nanomolar range. This suggests that these HPsensors can be used as a sensitive indicator of protein surface hydrophobicity. A first principle approach is used to identify the molecular level mechanism for the substantial increase in the fluorescence signal strength. Our results show that conformational change and increased molecular rigidity of the dye due to its hydrophobic interaction with protein lead to fluorescence enhancement. PMID- 26679513 TI - Speckle lithography for fabricating Gaussian, quasi-random 2D structures and black silicon structures. AB - Laser speckle pattern is a granular structure formed due to random coherent wavelet interference and generally considered as noise in optical systems including photolithography. Contrary to this, in this paper, we use the speckle pattern to generate predictable and controlled Gaussian random structures and quasi-random structures photo-lithographically. The random structures made using this proposed speckle lithography technique are quantified based on speckle statistics, radial distribution function (RDF) and fast Fourier transform (FFT). The control over the speckle size, density and speckle clustering facilitates the successful fabrication of black silicon with different surface structures. The controllability and tunability of randomness makes this technique a robust method for fabricating predictable 2D Gaussian random structures and black silicon structures. These structures can enhance the light trapping significantly in solar cells and hence enable improved energy harvesting. Further, this technique can enable efficient fabrication of disordered photonic structures and random media based devices. PMID- 26679514 TI - Evaluation of bovine abortion cases and tissue suitability for identification of infectious agents in California diagnostic laboratory cases from 2007 to 2012. AB - Establishing a definitive cause of bovine abortion is a challenging problem faced by veterinary practitioners and diagnosticians. Detection of an infectious or noninfectious source for abortion may facilitate interventions that mitigate future fetal loss in the herd. The purposes of this study were to identify the most common causes of bovine abortion in cases submitted to the California Animal Health and Food Safety Laboratory System, Davis (CAHFS) from 2007 to 2013 and to determine if detection of infectious pathogens differed with the fetal tissue evaluated. Records of 665 bovine abortion cases of 709 animals were reviewed for pathologic diagnoses, test methods used to identify causative conditions, and which tissues yielded successful identification of infectious agents associated with abortion. Over 58% of abortions were attributed to an infectious cause and 46.9% had an infectious agent identified. The most common infectious conditions were Epizootic Bovine Abortion (EBA) (16.2% of all fetuses), other fetal bacterial infections (14.7% of all fetuses), and Neospora caninum (9.3% of all fetuses.) The bacterium associated with EBA (currently named Pajaroellobacter abortibovis) was most commonly identified by immunohistochemistry (IHC) in lymphoid organs (thymus and spleen); N. caninum IHC was most frequently positive in brain, kidney, and placenta. In cases of pathogenic and opportunistic bacterial infections, abomasal samples yielded a significantly greater proportion of definitive aerobic culture results than lung or liver tissues. Direct fluorescent antibody test results for Bovine Viral Diarrhea Virus testing were identical between lung and kidney tissues and nearly identical (96.0%) for Bovine Herpesvirus I. Noninfectious abortive conditions included fetal stress (10.5%), dystocia (3.9%), congenital defects (3.3%), toxicological or mineral problems (1.8%), and death of the cow (1.1%). Just over 20% of the aborted fetuses had no gross or histopathological lesions to explain the abortion. This review highlights the need for submission of critical samples including abomasal contents, lymphoid tissues (thymus, spleen, and lymph nodes), and brain to maximize the diagnosticians' ability to identify causes of abortion. PMID- 26679515 TI - A review of sexually transmitted bovine trichomoniasis and campylobacteriosis affecting cattle reproductive health. AB - The objective is to discuss sexually transmitted diseases caused by Tritrichomonas foetus (T foetus) and Campylobacter fetus (C fetus) subsp. venerealis, with a focus on prevalence, pathogenesis, and diagnosis in cows and bulls. Diagnosis and control are problematic because these diseases cause severe reproductive losses in cows, but in bulls are clinically asymptomatic, which allows the disease to flourish, especially in the absence of legislated control programs. We review research regarding prophylactic systemic immunization of bulls and cows with antigens of T foetus and C fetus venerealis and their efficacy in preventing or clearing preexisting infections in the genital tract. Current diagnostic methods of C fetus venerealis and T foetus (microbial culture and PCR) should be improved. Review of the latest advances in bovine trichomoniasis and campylobacteriosis should promote knowledge and provide an impetus to pursue further efforts to control bovine sexually transmitted diseases. PMID- 26679516 TI - A model for gene deregulation detection using expression data. AB - In tumoral cells, gene regulation mechanisms are severely altered. Genes that do not react normally to their regulators' activity can provide explanations for the tumoral behavior, and be characteristic of cancer subtypes. We thus propose a statistical methodology to identify the misregulated genes given a reference network and gene expression data. PMID- 26679517 TI - B-cell depletion in autoimmune hepatitis: Is it safe for the bowel? PMID- 26679518 TI - A toxic endophyte-infected grass helps reverse degradation and loss of biodiversity of over-grazed grasslands in northwest China. AB - Overgrazing of China's grasslands is increasingly causing biodiversity to decline. In degenerated grasslands of northwest China endophyte (Epichloe gansuensis) infected Achnatherum inebrians (drunken horse grass) is becoming widely distributed because of its toxicity to livestock. In this study, we investigated the ecological consequences of endophyte toxicity in this native grass, at three sites in northwest China, by comparing seed production of plant species and arthropod abundance in overgrazed grasslands with and without the presence of A. inebrians. Our findings demonstrate that the presence of endophyte infected A. inebrians reduces the loss of plant and arthropod biodiversity by providing a protected nursery free of animal grazing. Therefore, A. inebrians, typically regarded as an unwanted toxic invader by pastoralists, should be viewed as beneficial for grasslands as its presence maintains plant and arthropod biodiversity, and provides a foundation stone in the reconstruction and restoration of these grassland ecosystems. PMID- 26679519 TI - Simultaneous Production of High-Performance Flexible Textile Electrodes and Fiber Electrodes for Wearable Energy Storage. AB - High-performance flexible textile electrodes and fiber electrodes are produced simultaneously by a newly proposed effective strategy. Activated carbon fiber cloth (ACFC)/carbon nanotubes (CNTs) and ACFC/MnO2/CNTs composites are designed as high-performance flexible textile electrodes. Theses textiles can also be easily dismantled into individual fiber bundles used as high-performance flexible fiber electrodes. PMID- 26679520 TI - Erratum: Non-perturbative effects in spin glasses. PMID- 26679522 TI - The limits of metrical segmentation: intonation modulates infants' extraction of embedded trochees. AB - We tested German nine-month-olds' reliance on pitch and metrical stress for segmentation. In a headturn-preference paradigm, infants were familiarized with trisyllabic words (weak-strong-weak (WSW) stress pattern) in sentence-contexts. The words were presented in one of three naturally occurring intonation conditions: one in which high pitch was aligned with the stressed syllable and two misalignment conditions (with high pitch preceding vs. following the stressed syllable). Infants were tested on the SW unit of the WSW carriers. Experiment 1 showed recognition only when the stressed syllable was high-pitched. Intonation of test items (similar vs. dissimilar to familiarization) had no influence (Experiment 2). Thus, German nine-month-olds perceive stressed syllables as word onsets only when high-pitched, although they already generalize over different pitch contours. Different mechanisms underlying this pattern of results are discussed. PMID- 26679523 TI - Electrohydrodynamic manipulation of particles adsorbed on the surface of a drop. AB - In our previous studies we have shown that particles adsorbed on the surface of a drop can be concentrated at its poles or equator by applying a uniform electric field. This happens because even when the applied electric field is uniform the electric field on the surface of the drop is nonuniform, and so particles adsorbed on the surface are subjected to dielectrophoretic (DEP) forces. In this paper, we study the behavior of adsorbed particles at low electric field frequencies when the drop and ambient liquids are weakly conducting dielectric liquids, and model it using a leaky dielectric model. The electrohydrodynamic (EHD) flow which arises because of the accumulation of charge on the surface of the drop can be from pole-to-equator or equator-to-pole depending on the properties of the drop and ambient liquids. The flow however diminishes with increasing frequency and there is a critical frequency at which the drag force on a particle due to the EHD flow becomes equal to the DEP force, and above this critical frequency the DEP force dominates. When the fluid and particles properties are such that the EHD and DEP forces are in the opposite directions, particles can be collected at the poles or the equator, and also can be moved from the poles to the equator, or vice versa, by varying the frequency. Also, it is possible to separate the particles of a binary mixture when the critical frequencies of the two types of particles are different. PMID- 26679521 TI - The ubiquitin ligase Smurf2 suppresses TGFbeta-induced epithelial-mesenchymal transition in a sumoylation-regulated manner. AB - Epithelial-mesenchymal transition (EMT) is a fundamental cellular process in epithelial tissue development, and can be reactivated in cancer contributing to tumor invasiveness and metastasis. The cytokine transforming growth factor-beta (TGFbeta) is a key inducer of EMT, but the mechanisms that regulate TGFbeta induced EMT remain incompletely understood. Here, we report that knockdown of the ubiquitin ligase Smurf2 promotes the ability of TGFbeta to induce EMT in a three dimensional cell culture model of NMuMG mammary epithelial cells. In other studies, we identify Smurf2 as a target of the small ubiquitin like modifier (SUMO) pathway. We find that the SUMO-E2 conjugating enzyme Ubc9 and the SUMO E3 ligase PIAS3 associate with Smurf2 and promote its sumoylation at the distinct sites of Lysines 26 and 369. The sumoylation of Smurf2 enhances its ability to induce the degradation of the TGFbeta receptor and thereby suppresses EMT in NMuMG cells. Collectively, our data reveal that Smurf2 acts in a sumoylation regulated manner to suppress TGFbeta-induced EMT. These findings have significant implications for our understanding of epithelial tissue development and cancer. PMID- 26679524 TI - [Retinoblastoma update]. AB - Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of 2 years, and in most cases they are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of 1 year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10-15% of children with a unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms at diagnosis are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, location), the risks for vision, and the possible hereditary nature of the disease. The main prognostic aspects are still early detection and adapted coverage by a multidisciplinary, highly specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is made according to the histological risk factors. The most important recent therapeutic advances concern conservative treatment, which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy, or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion and intravitreal injections, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblastoma is now excellent in industrialized countries, but long-term survival is still related to the development of secondary tumors, mainly secondary sarcoma. Retinoblastoma requires multidisciplinary care as well as a long-term specialized follow-up. Early counseling of patients and their family concerning the risk of transmission of the disease and the risk of development of secondary tumors is necessary. PMID- 26679526 TI - Green-synthesised nanoparticles from Melia azedarach seeds and the cyclopoid crustacean Cyclops vernalis: an eco-friendly route to control the malaria vector Anopheles stephensi? AB - The impact of green-synthesised mosquitocidal nanoparticles on non-target aquatic predators is poorly studied. In this research, we proposed a single-step method to synthesise silver nanoparticles (Ag NP) using the seed extract of Melia azedarach. Ag NP were characterised using a variety of biophysical methods, including UV-vis spectrophotometry, scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. In laboratory assays on Anopheles stephensi, Ag NP showed LC50 ranging from 2.897 (I instar larvae) to 14.548 ppm (pupae). In the field, the application of Ag NP (10 * LC50) lead to complete elimination of larval populations after 72 h. The application of Ag NP in the aquatic environment did not show negative adverse effects on predatory efficiency of the mosquito natural enemy Cyclops vernalis. Overall, this study highlights the concrete possibility to employ M. azedarach synthesised Ag NP on young instars of malaria vectors. PMID- 26679527 TI - Neuroanatomical anomalies of dyslexia: Disambiguating the effects of disorder, performance, and maturation. AB - An increasing body of studies has revealed neuroanatomical impairments in developmental dyslexia. However, whether these structural anomalies are driven by dyslexia (disorder-specific effects), absolute reading performance (performance dependent effects), and/or further influenced by age (maturation-sensitive effects) remains elusive. To help disentangle these sources, the current study used a novel disorder (dyslexia vs. control) by maturation (younger vs. older) factorial design in 48 Chinese children who were carefully matched. This design not only allows for direct comparison between dyslexics versus controls matched for chronological age and reading ability, but also enables examination of the influence of maturation and its interaction with dyslexia. Voxel-based morphometry (VBM) showed that dyslexic children had reduced regional gray matter volume in the left temporo-parietal cortex (spanning over Heschl's gyrus, planum temporale and supramarginal gyrus), middle frontal gyrus, superior occipital gyrus, and reduced regional white matter in bilateral parieto-occipital regions (left cuneus and right precuneus) compared with both age-matched and reading level matched controls. Therefore, maturational stage-invariant neurobiological signatures of dyslexia were found in brain regions that have been associated with impairments in the auditory/phonological and attentional systems. On the other hand, maturational stage-dependent effects on dyslexia were observed in three regions (left ventral occipito-temporal cortex, left dorsal pars opercularis and genu of the corpus callosum), all of which were previously reported to be involved in fluent reading and its development. These striking dissociations collectively suggest potential atypical developmental trajectories of dyslexia, where underlying mechanisms are currently unknown but may be driven by interactions between genetic and/or environmental factors. In summary, this is the first study to disambiguate maturational stage on neuroanatomical anomalies of dyslexia in addition to the effects of disorder, reading performance and maturational stage on neuroanatomical anomalies of dyslexia, despite the limitation of a relatively small sample-size. These results will hopefully encourage future research to place greater emphasis on taking a developmental perspective to dyslexia, which may, in turn, further our understanding of the etiological basis of this neurodevelopmental disorder, and ultimately optimize early identification and remediation. PMID- 26679528 TI - Impact of store-and-forward (SAF) teledermatology on outpatient dermatologic care: A prospective study in an underserved urban primary care setting. AB - BACKGROUND: The clinical value of teledermatology in the primary care setting remains relatively unknown. OBJECTIVE: We sought to determine the impact of teledermatology on outpatient diagnosis, management, and access to dermatologic care in a resource-poor primary care setting. METHODS: We performed a prospective study of store-and-forward teledermatology consults submitted between January and November 2013 from 11 underserved clinics in Philadelphia to the University of Pennsylvania using mobile devices and the Internet. We assessed diagnostic and management concordance between primary care providers and dermatologists, time to consult completion, anticipated level of dermatology input in the absence of teledermatology, and number of consults managed with teledermatology alone. RESULTS: The study included 196 consults encompassing 206 dermatologic conditions. Diagnoses and management plans of primary care providers and dermatologists were fully concordant for 22% and 23% of conditions, respectively. The median time to consult completion was 14 (interquartile range 3-28) hours. At least 61% of consults would not otherwise have received dermatology input, and 77% of consults were managed with teledermatology alone. LIMITATIONS: Lack of a diagnostic gold standard, limited patient follow-up, and uncertain generalizability are limitations. CONCLUSION: Teledermatology is an innovative and impactful modality for delivering dermatologic care to outpatients in resource-poor primary care settings. PMID- 26679530 TI - Strengthening Community Capacity for Environmental Health Promotion through Photovoice. AB - OBJECTIVE(S): The study aims were to: (1) Identify health promoters'; perceptions of housing issues faced by farmworker families in an agricultural community, and (2) Strengthen community capacity to promote healthy and affordable housing. DESIGN AND SAMPLE: Photovoice was used to identify participants'; perceptions about farmworker housing. Thematic analysis was used to analyze participant interviews. Freudenberg's "Community Capacity for Environmental Health Promotion" framework was used to organize activities that contributed to strengthening community capacity. Purposive sampling was used to recruit six bilingual health promoters into the study. MEASURES: A demographic questionnaire was administered to characterize participants. An interview guide was used to inquire about housing conditions and the research process. A tracking tool was used to document capacity-building activities 2 years post data collection. RESULTS: Housing issues faced by farmworker families included housing availability, poor conditions, and invisibility. All dimensions of community capacity were represented. Most occurred on an individual level. CONCLUSIONS: Health promoters identified housing issues and built community capacity to support farmworker housing. Nurses can support housing initiatives by assessing housing status, using data to support healthy housing, supporting health promoter programs in new service delivery models, and leading coalitions to address housing as a social determinant of health. PMID- 26679529 TI - Selenium isotope evidence for progressive oxidation of the Neoproterozoic biosphere. AB - Neoproterozoic (1,000-542 Myr ago) Earth experienced profound environmental change, including 'snowball' glaciations, oxygenation and the appearance of animals. However, an integrated understanding of these events remains elusive, partly because proxies that track subtle oceanic or atmospheric redox trends are lacking. Here we utilize selenium (Se) isotopes as a tracer of Earth redox conditions. We find temporal trends towards lower delta(82/76)Se values in shales before and after all Neoproterozoic glaciations, which we interpret as incomplete reduction of Se oxyanions. Trends suggest that deep-ocean Se oxyanion concentrations increased because of progressive atmospheric and deep-ocean oxidation. Immediately after the Marinoan glaciation, higher delta(82/76)Se values superpose the general decline. This may indicate less oxic conditions with lower availability of oxyanions or increased bioproductivity along continental margins that captured heavy seawater delta(82/76)Se into buried organics. Overall, increased ocean oxidation and atmospheric O2 extended over at least 100 million years, setting the stage for early animal evolution. PMID- 26679531 TI - Effects of episodic future thinking on discounting: Personalized age-progressed pictures improve risky long-term health decisions. AB - Many everyday choices are associated with both delayed and probabilistic outcomes. The temporal attention hypothesis suggests that individuals' decision making can be improved by focusing attention on temporally distal events and implies that environmental manipulations that bring temporally distal outcomes into focus may alter an individual's degree of discounting. One such manipulation, episodic future thinking, has shown to lower discount rates; however, several questions remain about the applicability of episodic future thinking to domains other than delay discounting. The present experiments examine the effects of a modified episodic-future-thinking procedure in which participants viewed age-progressed computer-generated images of themselves and answered questions related to their future, on probability discounting in the context of both a delayed health gain and loss. Results indicate that modified episodic future thinking effectively altered individuals' degree of discounting in the predicted directions and demonstrate the applicability of episodic future thinking to decision making of socially significant outcomes. PMID- 26679532 TI - High Fluorescence Efficiencies and Large Stokes Shifts of Folded Fluorophores Consisting of a Pair of Alkenyl-Tethered, pi-Stacked Oligo-p-phenylenes. AB - A series of pure hydrocarbon fluorophores containing a pair of pi-stacked oligo-p phenylenes have been synthesized and analyzed by NMR and X-ray crystallography. They show good fluorescence in solutions and enhanced fluorescence in the aggregated state. Large Stokes shifts (up to 214 nm) have been achieved in these folded fluorophores in virtue of intramolecular energy transfer, and balanced structural rigidity and flexibility. These folded fluorophores provide perfect models for understanding the energy and charge transfer process in pi-stacked systems. PMID- 26679533 TI - Allogeneic hematopoietic cell transplantation in systemic mastocytosis: is there a high risk for veno-occlusive disease? PMID- 26679534 TI - Staphylococcus aureus and its Bearing on Ophthalmic Disease. AB - PURPOSE: To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus. METHODS: Review of the current and prospective approaches for treating S. aureus endophthalmitis. RESULTS: Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries. CONCLUSIONS: With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential. PMID- 26679535 TI - The impact of ethnicity/race on the association between the Veterans Aging Cohort Study (VACS) Index and neurocognitive function among HIV-infected persons. AB - The Veterans Aging Cohort Study (VACS) Index was developed as a risk index for health outcomes in HIV, and it has been consistently associated with mortality. It shows a significant, yet relatively weak, association with neurocognitive impairment, and little is known about its utility among ethnic/racial minority groups. We examined whether the association between the VACS Index and neurocognition differed by ethnic/racial group. Participants included 674 HIV infected individuals (369 non-Hispanic whites, 111 non-Hispanic blacks, and 194 Hispanics). Neurocognitive function was assessed via a comprehensive battery. Scaled scores for each neurocognitive test were averaged to calculate domain and global neurocognitive scores. Models adjusting for demographics and HIV disease characteristics not included in the VACS Index showed that higher VACS Index scores (indicating poorer health) were significantly associated with worse global neurocognition among non-Hispanic whites. This association was comparable in non Hispanic blacks, but nonsignificant among Hispanics (with similar results for English and Spanish speaking). We obtained comparable findings in analyses adjusting for other covariates (psychiatric and medical comorbidities and lifestyle factors). Analyses of individual neurocognitive domains showed similar results in learning and delayed recall. For other domains, there was an effect of the VACS Index and no significant interactions with race/ethnicity. Different components of the VACS Index were associated with global neurocognition by race/ethnicity. In conclusion, the association between the VACS Index and neurocognitive function differs by ethnic/racial group. Identifying key indicators of HIV-associated neurocognitive impairment by ethnic/racial group might play an important role in furthering our understanding of the biomarkers of neuroAIDS. PMID- 26679536 TI - Seronegative neuromyelitis optica presenting with life-threatening respiratory failure. AB - CONTEXT: Dyspnea has rarely been reported as a presenting symptom in patients with neuromyelitis optica (NMO). We report an unusual case of NMO relapse presenting with rapidly progressive respiratory failure and briefly discuss the possible pathophysiological mechanisms of this potential life-threatening complication of NMO. FINDINGS: The 58-year-old woman with a history of bilateral optic neuritis presented to the emergency department with rapidly worsening dyspnea. Cervical spine magnetic resonance imaging showed extensive abnormal signal with involvement of the medulla oblongata. Since in our patient chest radiography failed to disclose a diaphragmatic palsy that is commonly observed in patients with phrenic nerve involvement, this acute manifestation of the disease may be attributed to brainstem involvement instead of cervical myelitis. CONCLUSION/CLINICAL RELEVANCE: Clinicians should be aware of this atypical presentation of NMO, which needs to be promptly recognized and aggressively treated. PMID- 26679538 TI - Effects of Different Blood Glucose Levels on Critically Ill Patients in an Intensive Care Unit. AB - AIMS: We explore the infection incidence and possible prognostic outcome relevance for patients with different blood glucose levels in an intensive care unit (ICU). METHODS: A total of 98 cases were enrolled and divided into three groups based on average fasting blood glucose levels (group A: <= 6.1 mmol/l; group B: 6.1-10 mmol/l; group C: >= 10 mmol/l). RESULTS: There were no statistical differences in the time to ICU admission, the indwelling durations of gastric tubes, urinary or deep vein catheters, tracheal intubations and tracheotomies, or the length of ventilator use (all p > 0.05). No evident difference in the multiple organ dysfunction syndrome rate was found between the three groups (p = 0.226). The infection and mortality rates between the groups showed significant differences (all p < 0.05). Furthermore, the difference of respiratory system infections was statistically significant among the three groups (p = 0.008), yet no such statistical difference was observed among groups regarding nonrespiratory system infections (p = 0.227). CONCLUSIONS: Critically ill patients with a high blood glucose level were positively correlated with a relatively high APACHE II score and more serious degree of disease, as well as a higher incidence of respiratory infection during their ICU stay than those with lower blood glucose levels (<10 mmol/l). PMID- 26679537 TI - CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System. AB - Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9 dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID- 26679540 TI - EBV and memory B cells: an affair with consequences. PMID- 26679541 TI - Idelalisib has CLL on the run! PMID- 26679539 TI - Transcriptome-wide RNA processing kinetics revealed using extremely short 4tU labeling. AB - BACKGROUND: RNA levels detected at steady state are the consequence of multiple dynamic processes within the cell. In addition to synthesis and decay, transcripts undergo processing. Metabolic tagging with a nucleotide analog is one way of determining the relative contributions of synthesis, decay and conversion processes globally. RESULTS: By improving 4-thiouracil labeling of RNA in Saccharomyces cerevisiae we were able to isolate RNA produced during as little as 1 minute, allowing the detection of nascent pervasive transcription. Nascent RNA labeled for 1.5, 2.5 or 5 minutes was isolated and analyzed by reverse transcriptase-quantitative polymerase chain reaction and RNA sequencing. High kinetic resolution enabled detection and analysis of short-lived non-coding RNAs as well as intron-containing pre-mRNAs in wild-type yeast. From these data we measured the relative stability of pre-mRNA species with different high turnover rates and investigated potential correlations with sequence features. CONCLUSIONS: Our analysis of non-coding RNAs reveals a highly significant association between non-coding RNA stability, transcript length and predicted secondary structure. Our quantitative analysis of the kinetics of pre-mRNA splicing in yeast reveals that ribosomal protein transcripts are more efficiently spliced if they contain intron secondary structures that are predicted to be less stable. These data, in combination with previous results, indicate that there is an optimal range of stability of intron secondary structures that allows for rapid splicing. PMID- 26679542 TI - The Rap1-RIAM pathway prefers beta2 integrins. PMID- 26679543 TI - To stimulate the phagocytes. PMID- 26679544 TI - TRALI: hit by CRP. PMID- 26679545 TI - GVHD meets GWAS. PMID- 26679546 TI - First case of acute generalized exanthematous pustulosis caused by pitavastatin: possible pathogenetic role of IL-36. PMID- 26679547 TI - Chirality-dependent structuration of protonated or sodiated polyphenylalanines: IRMPD and ion mobility studies. AB - Ion mobility experiments are combined with Infra-Red Multiple Photon Dissociation (IRMPD) spectroscopy and quantum chemical calculations for assessing the role of chirality in the structure of protonated and sodiated di- or tetra-peptides. Sodiated systems show a strong chirality dependence of the competition between Na(+)O and Na(+)pi interactions. Chirality effects are more subtle in protonated systems and manifest themselves by differences in the secondary interactions such hydrogen bonds between neutral groups or those involving the aromatic rings. PMID- 26679549 TI - Do we have sufficient data to use nongated CT for cardiovascular risk stratification? PMID- 26679548 TI - Computed Tomography Imaging in Patients with Congenital Heart Disease, Part 2: Technical Recommendations. An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT): Endorsed by the Society of Pediatric Radiology (SPR) and the North American Society of Cardiac Imaging (NASCI). PMID- 26679550 TI - An Alternative Method of Intermaxillary Fixation for Simple Pediatric Mandible Fractures. AB - PURPOSE: Mandibular fractures represent a substantial portion of facial fractures in the pediatric population. Pediatric mandibles differ from their adult counterparts in the presence of mixed dentition. Avoidance of injury to developing tooth follicles is critical. Simple mandibular fractures can be treated with intermaxillary fixation (IMF) using arch bars or bone screws. This report describes an alternative to these methods using silk sutures and an algorithm to assist in treating simple mandibular fractures in the pediatric population. PATIENTS AND METHODS: A retrospective chart review was performed and the records of 1 surgeon were examined. Pediatric patients who underwent treatment for a mandibular fracture in the operating room from 2011 to 2015 were identified using Common Procedural Terminology codes. Data collected included age, gender, type of fracture, type of treatment used, duration of fixation, and presence of complications. RESULTS: Five patients with a mean age of 6.8 years at presentation were identified. Fracture types were unilateral fractures of the condylar neck (n = 3), bilateral fractures of the condylar head (n = 1), and a unilateral fracture of the condylar head with an associated parasymphyseal fracture (n = 1). IMF was performed in 4 patients using silk sutures, and bone screw fixation was performed in the other patient. No post-treatment complications or malocclusion were reported. Average duration of IMF was 18.5 days. CONCLUSIONS: An algorithm is presented to assist in the treatment of pediatric mandibular fractures. Silk suture fixation is a viable and safe alternative to arch bars or bone screws for routine mandibular fractures. PMID- 26679551 TI - Guided Bone Regeneration Using Demineralized Dentin Matrix: Long-Term Follow-Up. AB - PURPOSE: This case report reviews the long-term clinical outcomes of using demineralized dentin matrix (autogenous tooth bone graft material [AutoBT]) in 5 cases that were first reported in 2010. MATERIALS AND METHODS: Cone-beam computerized tomography was used to measure the height and width of the graft to determine the change in bone area from immediately after surgery to final follow up (average, 5 yr 5.8 months). Corticocancellous bone formation and marginal bone resorption also were evaluated histologically 3 to 6 months after grafting, which focused mainly on remodeling capacities. RESULTS: Decreases in buccal height and alveolar ridge width ranged from -0.4 to -3.3 mm and from -0.4 to -4.2 mm, respectively. The change in bone area ranged from -8.1 to -36.2%. Corticocancellous bone had formed and was maintained successfully except for 1 mm of buccal marginal bone resorption in 1 case followed for 6 years 7 months. CONCLUSION: AutoBT, which was first reported for guided bone regeneration, showed that the corticocancellous bone that had formed had been maintained successfully with an implant after an average follow-up of 5 years. Although the number of samples was small, the results were consistent with those of other short-term follow-up studies on AutoBT. PMID- 26679552 TI - Hyaluronic Acid Versus Ultrasonic Resorbable Pin Fixation for Space Maintenance in Non-Grafted Sinus Lifting. AB - PURPOSE: An ultrasonic resorbable pin (SonicWeld, KLS Martin, Muhlheim, Germany) was compared with hyaluronic acid (Hyaloss Matrix, Anika Therapeutics, Bedford, MA) for their ability to maintain space in non-grafted sinus lifting. MATERIALS AND METHODS: A comparative split-mouth study was designed and implemented. Six women and 4 men were included (mean age, 56.7 yr). The primary predictors hyaluronic acid (HA) application and ultrasonic resorbable pin fixation (URPF) were coded as binary variables. The primary outcome variables were height of alveolar bone (HAB) and reduction in sinus volume (RSV). Secondary outcomes were bone density and implant survival. RESULTS: The postoperative mean HAB was significantly higher than the preoperative mean HAB on the 2 sides (P < .05). Mean increases in HAB and RSV on the URPF side were significantly greater than those on the HA side (P < .05). In total, patients were treated with 40 implants. No type I bone quality was identified; 14 (35%) implants were inserted in type II bone, 22 (50%) in type III bone, and 6 (15%) in type IV bone. There was no statistically meaningful difference between the 2 sides for implant survival or bone quality. At 6 months, all implants were clinically stable and the definitive prostheses were functional, resulting in a survival rate of 100%. CONCLUSIONS: There was sufficient bone height to eventually place implants on the 2 sides in all patients. The 2 techniques yielded predictable outcomes in implant survival and bone quality. However, HAB and RSV were considerably greater on the URPF side. PMID- 26679554 TI - Histopathological Features of Secondary Squamous Cell Carcinoma Around a Dental Implant in the Mandible After Chemoradiotherapy: A Case Report With a Clinicopathological Review. AB - Oral squamous cell carcinoma (OSCC) around a dental implant is a rare pathologic condition. This report describes a case of recurrent OSCC surrounding a dental implant, histopathologic findings, and a literature review of this condition. A 58-year-old Japanese woman underwent chemoradiotherapy for OSCC in the right lower gingiva, resulting in a complete response. Nine years after primary chemoradiotherapy, a dental implant was placed in her atrophic mandible. Three years later, an OSCC developed around the dental implant in the right lower premolar region. Marginal mandibulectomy was performed. Microscopic examination showed medullary invasion around the implant surface, suggesting that tumor infiltration of the bone was through the interface between the implant and bone. However, no downward invasion through the interface was evident. OSCC can develop around dental implants that are placed for oral rehabilitation after ablative surgery. Staging of OSCC and planning of surgical management should be carried out carefully, because implants placed adjacent to the OSCC can influence tumor invasion. A high degree of vigilance for OSCC is required during follow-up of patients with dental implants who have OSCC risk factors such as premalignant lesions. Detailed evaluation, including biopsy examination, is essential for distinguishing peri-implantitis from OSCC. PMID- 26679553 TI - Primary Ewing Family of Tumors of the Jaw Has a Better Prognosis Compared to Tumors of Extragnathic Sites. AB - PURPOSE: Primary Ewing sarcoma of the jaw is rare. The aim of this study was to describe new cases of primary Ewing sarcoma of the jaw and investigate reported prognostic factors of Ewing sarcoma in this series and treatment outcome. MATERIALS AND METHODS: Six patients with primary Ewing sarcoma of the jaw were treated at the Memorial Sloan Kettering Cancer Center (MSKCC) from 1992 through 2013. Clinical data, pathology reports, treatment prescribed, treatment regimens, outcome, and follow-up information were reviewed. RESULTS: Five of 6 patients were female and 5 cases were in the mandible. No patient presented with metastatic disease at diagnosis. All cases were positive for CD99, and 3 patients with genetic confirmation were positive for EWS-FLI1 fusion or EWSR1 gene rearrangement. All patients received induction multiagent chemotherapy and surgical resection and 2 patients received adjuvant radiotherapy. Total (grade IV) or nearly total (grade III) tumor necrosis in 3 of 5 patients (60%) assessed for histologic response to chemotherapy indicated intense sensitivity. All patients were alive and free of disease, with no history of local recurrence, at a median follow-up period of 6.5 years. CONCLUSION: Patients with primary Ewing sarcoma of the jaw have a good prognosis and metastasis is an uncommon occurrence at initial presentation. PMID- 26679555 TI - In search of perfect reads. AB - BACKGROUND: Continued advances in next generation short-read sequencing technologies are increasing throughput and read lengths, while driving down error rates. Taking advantage of the high coverage sampling used in many applications, several error correction algorithms have been developed to improve data quality further. However, correcting errors in high coverage sequence data requires significant computing resources. METHODS: We propose a different approach to handle erroneous sequence data. Presently, error rates of high-throughput platforms such as the Illumina HiSeq are within 1%. Moreover, the errors are not uniformly distributed in all reads, and a large percentage of reads are indeed error-free. Ability to predict such perfect reads can significantly impact the run-time complexity of applications. We present a simple and fast k-spectrum analysis based method to identify error-free reads. The filtration process to identify and weed out erroneous reads can be customized at several levels of stringency depending upon the downstream application need. RESULTS: Our experiments show that if around 80% of the reads in a dataset are perfect, then our method retains almost 99.9% of them with more than 90% precision rate. Though filtering out reads identified as erroneous by our method reduces the average coverage by about 7%, we found the remaining reads provide as uniform a coverage as the original dataset. We demonstrate the effectiveness of our approach on an example downstream application: we show that an error correction algorithm, Reptile, which rely on collectively analyzing the reads in a dataset to identify and correct erroneous bases, instead use reads predicted to be perfect by our method to correct the other reads, the overall accuracy improves further by up to 10%. CONCLUSIONS: Thanks to the continuous technological improvements, the coverage and accuracy of reads from dominant sequencing platforms have now reached an extent where we can envision just filtering out reads with errors, thus making error correction less important. Our algorithm is a first attempt to propose and demonstrate this new paradigm. Moreover, our demonstration is applicable to any error correction algorithm as a downstream application, this in turn gives a new class of error correcting algorithms as a by product. PMID- 26679556 TI - Fluorogenic Labeling of 5-Formylpyrimidine Nucleotides in DNA and RNA. AB - 5-Formylcytosine (5fC) and 5-formyluracil (5fU) are natural nucleobase modifications that are generated by oxidative modification of 5-methylcytosine and thymine (or 5-methyluracil). Herein, we describe chemoselective labeling of 5 formylpyrimidine nucleotides in DNA and RNA by fluorogenic aldol-type condensation reactions with 2,3,3-trimethylindole derivatives. Mild and specific reaction conditions were developed for 5fU and 5fC to produce hemicyanine-like chromophores with distinct photophysical properties. Residue-specific detection was established by fluorescence readout as well as primer-extension assays. The reactions were optimized on DNA oligonucleotides and were equally suitable for the modification of 5fU- and 5fC-modified RNA. This direct labeling approach of 5 formylpyrimidines is expected to help in elucidating the occurrence, enzymatic transformations, and functional roles of these epigenetic/epitranscriptomic nucleobase modifications in DNA and RNA. PMID- 26679557 TI - Decreasing After-Hours Hemodialysis in Hospitals. PMID- 26679558 TI - Exosomes: The missing link between microchimerism and acquired tolerance? AB - It has become increasingly clear that the immune system of viviparous mammals is much more in the business of acquiring tolerance to non-self antigens, than it is in rejecting cells that express them (for a recent review, highlighting the role of Treg cells, see ref. (1) ). It is also clear that both self-tolerance, and acquired tolerance to non-self is a dynamic process, with a natural ebb and flow. As has been often said of an effective team defense in sports, tolerance will "bend but does not break." How microchimerism, defined as the presence of extremely rare [1/10(4)-1/10(6)] cells of a genetically different individual, can induce either new immunogenetic pressures that push self-tolerance to the breaking point, or alternatively, provide relief from pre-existing immunogenetic risk, preventing development of autoimmune disease, remains a mystery. Indeed, the inability to directly correlate DNA-level microchimerism detected in blood samples by qPCR, with naturally occurring regulation to minor H and MHC alloantigens expressed by the rare cells themselves, has been frustrating to researchers in this field. (2) [Haynes, W.J. et al, this issue] However, recent developments in the areas of transplantation and reproductive immunology offer clues to how the effects of microchimerism can be amplified, and how a disproportionate immune impact might occur from a very limited cell source. PMID- 26679559 TI - Effect of high pressure processing on dispersive and aggregative properties of almond milk. AB - BACKGROUND: A study was conducted to investigate the impact of high pressure (450 and 600 MPa at 30 degrees C) and thermal (72, 85 and 99 degrees C at 0.1 MPa) treatments on dispersive and aggregative characteristics of almond milk. Experiments were conducted using a kinetic pressure testing unit and water bath. Particle size distribution, microstructure, UV absorption spectra, pH and color changes of processed and unprocessed samples were analyzed. RESULTS: Raw almond milk represented the mono model particle size distribution with average particle diameters of 2 to 3 um. Thermal or pressure treatment of almond milk shifted the particle size distribution towards right and increased particle size by five- to six-fold. Micrographs confirmed that both the treatments increased particle size due to aggregation of macromolecules. Pressure treatment produced relatively more and larger aggregates than those produced by heat treated samples. The apparent aggregation rate constant for 450 MPa and 600 MPa processed samples were k450MPa,30 degrees C = 0.0058 s(-1) and k600MPa,30 degrees C = 0.0095 s(-1) respectively. CONCLUSIONS: This study showed that dispersive and aggregative properties of high pressure and heat-treated almond milk were different due to differences in protein denaturation, particles coagulation and aggregates morphological characteristics. Knowledge gained from the study will help food processors to formulate novel plant-based beverages treated with high pressure. (c) 2015 Society of Chemical Industry. PMID- 26679560 TI - Absence of vancomycin-resistant enterococci among highly ESBL-positive crows (Corvus splendens) foraging on hospital waste in Bangladesh. AB - BACKGROUND: Vancomycin-resistant enterococci (VRE) have emerged as a growing problem in hospitals; however, domesticated animals, poultry, and wild birds are acting as potential reservoirs. There is a knowledge gap in the Epidemiology of VRE from Bangladesh. METHODS: To study the prevalence of VRE and the mechanisms of resistance implicated among wild birds, 238 fecal samples were collected in 2010 from house crows (Corvus splendens) foraging on hospital waste in Bangladesh. Fecal samples were screened by analyzing color change in broth and screening for vanA and vanB resistant genes by PCR. RESULTS: Neither vanA nor vanB genes were detected from the fecal samples. The house crow does not seem to constitute a reservoir for VRE. CONCLUSION: The zero prevalence is an indication that foraging on hospital waste does not constitute a major risk of VRE carriage in house crows and this is the first study to focus on the prevalence of VRE from wild birds in Bangladesh. PMID- 26679561 TI - Spatio-temporal variation in prevalence of Rift Valley fever: a post-epidemic serum survey in cattle and wildlife in Kenya. AB - BACKGROUND: Rift Valley fever (RVF) is a fatal arthropod-borne zoonotic disease of livestock and humans. Since the identification of RVF in Kenya in the 1930s, repeated epizootics and epidemics coinciding with El Nino events have occurred in several locations in Africa and Saudi Arabia, causing mass deaths of livestock and humans. RVF is of great interest worldwide because of its negative effect on international livestock trade and its potential to spread globally. The latter is due to the increasing incidence of extreme climatic phenomena caused by global warming, as well as to the increase in global trade and international travel. How RVF is maintained and sustained between epidemics and epizootics is not clearly understood, but it has been speculated that wildlife reservoirs and trans-ovarian transmission in the vector may be important. Several studies have examined the role of wildlife and livestock in isolation or in a limited geographical location within the one country over a short time (usually less than a year). In this study, we examined the seroprevalence of anti-RVF antibodies in cattle and several wildlife species from several locations in Kenya over an inter-epidemic period spanning up to 7 years. METHODS: A serological survey of immunoglobulin G (IgG) antibodies to RVF using competitive ELISA was undertaken on 297 serum samples from different wildlife species at various locations in Kenya. The samples were collected between 2008 and 2015. Serum was also collected in 2014 from 177 cattle from Ol Pejeta Conservancy; 113 of the cattle were in close contact with wildlife and the other 64 were kept separate from buffalo and large game by an electric fence. RESULTS: The seroprevalence of RVF virus (RVFV) antibody was 11.6% in wildlife species during the study period. Cattle that could come in contact with wildlife and large game were all negative for RVFV. The seroprevalence was relatively high in elephants, rhinoceros, and buffalo, but there were no antibodies in zebras, baboons, vervet monkeys, or wildebeest. CONCLUSIONS: Diverse species in conservation areas are exposed to RVFV. RVFV exposure in buffalo may indicate distribution of the virus over wide geographical areas beyond known RVFV foci in Kenya. This finding calls for thorough studies on the epizootology of RVFV in specific wildlife species and locations. PMID- 26679562 TI - Sequence-Dependent Structure/Function Relationships of Catalytic Peptide-Enabled Gold Nanoparticles Generated under Ambient Synthetic Conditions. AB - Peptide-enabled nanoparticle (NP) synthesis routes can create and/or assemble functional nanomaterials under environmentally friendly conditions, with properties dictated by complex interactions at the biotic/abiotic interface. Manipulation of this interface through sequence modification can provide the capability for material properties to be tailored to create enhanced materials for energy, catalysis, and sensing applications. Fully realizing the potential of these materials requires a comprehensive understanding of sequence-dependent structure/function relationships that is presently lacking. In this work, the atomic-scale structures of a series of peptide-capped Au NPs are determined using a combination of atomic pair distribution function analysis of high-energy X-ray diffraction data and advanced molecular dynamics (MD) simulations. The Au NPs produced with different peptide sequences exhibit varying degrees of catalytic activity for the exemplar reaction 4-nitrophenol reduction. The experimentally derived atomic-scale NP configurations reveal sequence-dependent differences in structural order at the NP surface. Replica exchange with solute-tempering MD simulations are then used to predict the morphology of the peptide overlayer on these Au NPs and identify factors determining the structure/catalytic properties relationship. We show that the amount of exposed Au surface, the underlying surface structural disorder, and the interaction strength of the peptide with the Au surface all influence catalytic performance. A simplified computational prediction of catalytic performance is developed that can potentially serve as a screening tool for future studies. Our approach provides a platform for broadening the analysis of catalytic peptide-enabled metallic NP systems, potentially allowing for the development of rational design rules for property enhancement. PMID- 26679563 TI - Towards a sociology of healthcare safety and quality. AB - The contributions to this collection address technologies, practices, experiences and the organisation of quality and safety across a wide range of healthcare contexts. Spanning three continents, from hospital to community, maternity to mental health, they shine a light into the boardrooms, back offices and front lines of healthcare, offering sociological insights from the perspectives of managers, clinicians and patients. We review these articles and consider how they contribute to some of the dilemmas that confront mainstream approaches to quality and safety and then look ahead to outline future lines of sociological inquiry to progress the theory and practice of quality and safety. PMID- 26679565 TI - Acute endovascular recanalization: lessons from randomized controlled trials. AB - PURPOSE OF REVIEW: The purpose is to review the results and impact of recent positive studies on endovascular stroke treatment in the context of previous negative trials. RECENT FINDINGS: Since October 2014, the results of five randomized controlled multicenter trials on the endovascular stroke treatment as adjunct to conservative treatment (largely including intravenous tissue-type plasminogen activator) versus conservative treatment alone have been published. All of these trials largely used stent retrievers as endovascular device and included patients with proven large vessel occlusion (mostly distal internal carotid or proximal middle cerebral artery (M1), short time windows after stroke onset and mostly small infarctions on initial imaging. Over all there was an overwhelming beneficial effect on outcome measured as shift in the modified Rankin Scale score and independent survival, respectively. Moreover, the rate of adverse events, in particular hemorrhage rate, was not increased. These new findings contrast previous studies on endovascular stroke treatment using mostly first generation nonstent retriever devices, longer time windows and different imaging inclusion criteria, which were overall neutral for patient outcome. SUMMARY: Endovascular stroke treatment with stent retrievers is the standard of care in large vessel occlusion. New randomized controlled trials should investigate safety and efficacy in extended indications as advanced time windows or more extensive signs of ischemia on initial imaging. The same applies for new devices apart from stent retrievers. PMID- 26679566 TI - The vestibular system: balancing more than just the body. AB - PURPOSE OF REVIEW: The review presents a selection of recent studies in the field of vestibular neuroscience, including how vestibular stimulation modulates space and body perception. RECENT FINDINGS: Recent neuroimaging studies identified the operculo-insular/retroinsular cortex as the core vestibular cortex and showed how it is reorganized after vestibular dysfunctions. Subliminal galvanic vestibular stimulation (GVS) induces long-term reduction of hemispatial neglect and improves vertical perception in stroke patients, but the underlying mechanisms remain to be identified. Healthy volunteer research suggests that GVS and caloric vestibular stimulation (CVS) modulate visual and somatosensory processing and that beneficial effects of GVS/CVS in stroke patients are not limited to merely rebalancing brain hemispheric activity. Another mechanism would be that GVS/CVS anchors the self to the body, thus promoting an egocentric frame of reference. SUMMARY: In addition to 'balancing the body', the vestibular cortical network contributes to modulate space, body and self-awareness. Emerging evidence suggests that the vestibular network expands into dimensions of emotion processing, mental health, and social cognition. Here, the importance of connecting vestibular physiology, affective neuroscience, and social neuroscience to better understand the psychological aspects of vertigo in otoneurology is discussed. PMID- 26679567 TI - Recent advances in mesoscopic-scale imaging in animal models of ischemic stroke. AB - PURPOSE OF REVIEW: This article provides an overview of the recent literature regarding the application of in-vivo brain imaging techniques to animal models of ischemic stroke. RECENT FINDINGS: Major breakthroughs concerned the effects of sensory stimulation on neuronal function, local hemodynamics, and tissue outcome in the hyperacute phase of stroke; the novel application to stroke of hybrid scanners allowing simultaneous PET and magnetic resonance; the refinements of magnetic resonance-based oxygen imaging, allowing to map the ischemic penumbra in a completely noninvasive way; the implementation of new PET ligands to selectively map poststroke neuronal death and neuroinflammation; and the use of novel mesoscale imaging techniques to demonstrate the major role of interhemispheric connectivity in poststroke plasticity and functional recovery. SUMMARY: The array of techniques to map in vivo the key pathophysiological brain processes involved in stroke is currently enlarging at an amazing pace. This is paralleled by ever-increasing sophistication in postprocessing tools. The combination of techniques allowing simultaneous access to several variables is particularly powerful as it affords unprecedented insights into the intimate processes underlying the tissue and neuronal changes that follow a stroke. These major leaps forward will hopefully lead to therapeutic breakthroughs aiming at improving functional outcome after stroke. PMID- 26679568 TI - Lifestyle modification for stroke prevention: facts and fiction. AB - PURPOSE OF REVIEW: The purpose is to summarize recent evidence on lifestyle modifications and first or recurrent stroke risk. RECENT FINDINGS: Weight reduction, low-risk diet, regular physical activity, smoking cessation, and low to-moderate alcohol consumption may reduce stroke risk up to 50% or more, but level one evidence is still lacking for several interventions. Appropriate food ingredients can significantly decrease stroke risk as recently confirmed for Mediterranean diet. The optimal intensity and amount of physical exercise is still not well established before and after stroke, although modest levels of activity already show benefits. Passive smoking represents an important health hazard. The impact of tobacco withdrawal using e-cigarette is currently uncertain. Alcohol and stroke risk relation is probably J-shaped for ischaemic stroke and linear for intracranial haemorrhage. Coffee consumption is J-shaped for overall stroke. Several interventions have failed to show significant effects, including regular intake of 'healthy' forms of fatty acids, various vitamin supplements, and other antioxidants. Both individualized and public educational programmes are likely needed on a repetitive basis to induce and maintain a healthy lifestyle before or after a stroke. PMID- 26679564 TI - ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis. AB - BACKGROUND: Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. RESULTS: In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. CONCLUSIONS: Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots. PMID- 26679569 TI - Corticosteroids and the retina: a role for the mineralocorticoid receptor. AB - PURPOSE OF REVIEW: Long-lasting devices releasing steroids have been approved recently for macular edema of various origins. Identification of the retina as a novel mineralo-sensitive tissue also raises new therapeutic options. RECENT FINDINGS: Recently, the over activation of the mineralocorticoid receptor (MR) pathway has been shown to cause fluid accumulation in the retina, choroidal vasodilation, and to promote retinal neovascularization in hypoxic conditions. These findings indicate that MR antagonists could have beneficial effects in the treatment of retinal diseases. Central serous chorioretinopathy is a retinal disease associated with choroidal vasodilation and subretinal fluid that affects mostly men with type A personality and occurrence has been associated with steroid intake. In several independent studies, MR antagonists have shown beneficial effects, significantly reducing subretinal fluid in eyes of chronic central serous chorioretinopathy patients. SUMMARY: The role of MR in retinal disorder is emerging and the potential association with psychological traits is considered. The place of MR antagonists for retinal diseases treatment is discussed. PMID- 26679570 TI - Stroke: two steps forward, one step sideward. PMID- 26679571 TI - The glycolytic enzyme enolase represents a plasminogen-binding protein on the surface of a wide variety of medically important fungal species. AB - Allergies are an increasing issue in human health and can, eventually, cause severe anaphylactic shock. Aspergillus fumigatus and Candida albicans are leading causes of life-threatening invasive fungal infections in immunocompromised patients, but can also cause severe allergic responses in otherwise healthy individuals. The glycolytic enzyme enolase is known as a major allergen despite its function in intracellular metabolism. Therefore, its presentation on surfaces of different fungal species was investigated by using antibodies raised against recombinant enolases from A. fumigatus and C. albicans. Examination of antibody specificity revealed cross-reactivity to cell-free extracts from Aspergillus terreus, Aspergillus flavus, Aspergillus nidulans and Candida glabrata, but not against any of the three human enolases. Antibody specificity was further confirmed by hybridization with other recombinant fungal enolases, where the antibodies recognized different subsets of fungal enolases. When surface presentation of enolase was tested on intact fungal cells, a positive staining was obtained with those antibodies that also recognized the enzyme from the respective cell-free extract. This implies a general surface presentation of this glycolytic enzyme among fungal species and provides hints for its predominant recognition as an allergen. Additionally, A. fumigatus and C. albicans enolase bound to human plasminogen, which remained accessible for the plasminogen activator uPA. This implies a potential role of enolase in the invasion and dissemination process during fungal infections. PMID- 26679573 TI - Whole-Genome Sequences of Novel Porcine Circovirus Type 2 Viruses Detected in Swine from Mexico and the United States. AB - A unique porcine circovirus type 2 capsid protein (ORF2) sequence was detected in swine samples submitted to the Iowa State University Veterinary Diagnostic Laboratory. The complete genome sequences of four viruses, one from Mexico and three from the United States, were determined to further characterize this novel PCV2 genotype. PMID- 26679572 TI - Optimal radiotherapy dose schedules under parametric uncertainty. AB - We consider the effects of parameter uncertainty on the optimal radiation schedule in the context of the linear-quadratic model. Our interest arises from the observation that if inter-patient variability in normal and tumor tissue radiosensitivity or sparing factor of the organs-at-risk (OAR) are not accounted for during radiation scheduling, the performance of the therapy may be strongly degraded or the OAR may receive a substantially larger dose than the allowable threshold. This paper proposes a stochastic radiation scheduling concept to incorporate inter-patient variability into the scheduling optimization problem. Our method is based on a probabilistic approach, where the model parameters are given by a set of random variables. Our probabilistic formulation ensures that our constraints are satisfied with a given probability, and that our objective function achieves a desired level with a stated probability. We used a variable transformation to reduce the resulting optimization problem to two dimensions. We showed that the optimal solution lies on the boundary of the feasible region and we implemented a branch and bound algorithm to find the global optimal solution. We demonstrated how the configuration of optimal schedules in the presence of uncertainty compares to optimal schedules in the absence of uncertainty (conventional schedule). We observed that in order to protect against the possibility of the model parameters falling into a region where the conventional schedule is no longer feasible, it is required to avoid extremal solutions, i.e. a single large dose or very large total dose delivered over a long period. Finally, we performed numerical experiments in the setting of head and neck tumors including several normal tissues to reveal the effect of parameter uncertainty on optimal schedules and to evaluate the sensitivity of the solutions to the choice of key model parameters. PMID- 26679574 TI - Complete Genome Sequence of Mayaro Virus (Togaviridae, Alphavirus) Strain BeAr 20290 from Brazil. AB - We report here the complete genome sequence of Mayaro virus strain BeAr 20290 isolated from Haemagogus mosquitoes in 1960. The sequence presented here includes all nonstructural and structural proteins and the 5'- and 3'-untranslated (UTR) regions. PMID- 26679575 TI - Genome Sequences of 11 Brucella abortus Isolates from Persistently Infected Italian Regions. AB - Bovine brucellosis, typically caused by Brucella abortus, has been eradicated from much of the developed world. However, the disease remains prevalent in southern Italy, persisting as a public and livestock health concern. We report here the whole-genome sequences of 11 isolates from cattle (Bos taurus) and water buffalo (Bubalus bubalis) that are representative of the current genetic diversity of B. abortus lineages circulating in Italy. PMID- 26679576 TI - Complete Genome Sequence of Streptococcus anginosus J4211, a Clinical Isolate. AB - Streptococcus anginosus is an opportunistic human pathogen that causes abscesses of the brain, liver, and other organs. Here, we announce the complete genome sequence of a clinically isolated strain of S. anginosus J4211. The genome sequence contains two prophages and multiple mobile genetic elements. PMID- 26679577 TI - Complete Genome Sequence of Aneurinibacillus migulanus E1, a Gramicidin S- and d Phenylalanyl-l-Propyl Diketopiperazine-Deficient Mutant. AB - We report here the complete genome sequence of the Aneurinibacillus migulanus E1 mutant deficient in gramicidin S (GS) and d-phenylalanyl-l-propyl diketopiperazine (DKP) formation. The genome consists of a circular chromosome (6,301,904 bp, 43.20% G+C content) without any plasmid. The complete genome sequence enables further investigation of the biosynthetic mechanism and the biological function of gramicidin S. PMID- 26679578 TI - Draft Genome Sequence of Thermophilic Geobacillus sp. Strain Sah69, Isolated from Saharan Soil, Southeast Algeria. AB - Geobacillus spp. are potential sources of novel enzymes, such as those involved in the degradation of recalcitrant polymers. Here, we report a Geobacillus genome that may help reveal genomic differences between this strain and publicly available representatives of the same genus from diverse niches. PMID- 26679579 TI - Draft Genome Sequences of Edwardsiella ictaluri Strains LADL11-100 and LADL11-194 Isolated from Zebrafish Danio rerio. AB - Here, we report the draft genome sequences of Edwardsiella ictaluri strains LADL11-100 and LADL11-194, two isolates from natural outbreaks of edwardsiellosis in the zebrafish Danio rerio, as well as the sequences of the plasmids carried by the zebrafish strain of E. ictaluri. PMID- 26679580 TI - Complete Genome Sequence of a Tomato Isolate of Parietaria Mottle Virus from Italy. AB - We report here the complete genome sequence of isolate T32 of parietaria mottle virus (PMoV) infecting tomato plants in Turin, Italy, obtained by Sanger sequencing. T32 shares 90.48 to 96.69% nucleotide identity with other two PoMV isolates, CR8 and Pe1, respectively, whose complete genome sequences are available. PMID- 26679581 TI - Draft Genome Sequence of Streptomyces mutabilis TRM45540, Isolated from a Hypersaline Soil Sample. AB - We report here the draft genome sequence of Streptomyces mutabilis TRM45540, a strain isolated from a soil sample from Xinjiang, China. Analysis of the genome using the bioinformatics tool antiSMASH showed the presence of many unique natural-product biosynthetic pathways. PMID- 26679582 TI - Complete Genome Sequence of Xanthomonas campestris pv. campestris Strain 17 from Taiwan. AB - Xanthomonas campestris pv. campestris 17 is a Gram-negative bacterium that is phytopathogenic to cruciferous plants in Taiwan. The 4,994,426-bp-long genome consists of 24 contigs with 4,050 protein-coding genes, 1 noncoding RNA (ncRNA) gene, 6 rRNA genes, and 55 tRNA genes. PMID- 26679583 TI - Draft Genome Sequence of Pedobacter sp. Strain Hv1, an Isolate from Medicinal Leech Mucosal Castings. AB - The Pedobacter sp. Hv1 strain was isolated from the medicinal leech, Hirudo verbana, mucosal castings. These mucosal sheds have been demonstrated to play a role in horizontal symbiont transmission. Here, we report the draft 4.9 Mbp genome sequence of Pedobacter sp. strain Hv1. PMID- 26679584 TI - Draft Genome Sequence of CO33, a Coffee-Infecting Isolate of Xylella fastidiosa. AB - The draft genome sequence of Xylella fastidiosa CO33 isolate, retrieved from symptomatic leaves of coffee plant intercepted in northern Italy, is reported. The CO33 genome size is 2,681,926 bp with a GC content of 51.7%. PMID- 26679585 TI - Genome Sequences of Oblitimonas alkaliphila gen. nov. sp. nov. (Proposed), a Novel Bacterium of the Pseudomonadaceae Family. AB - Results obtained through 16S rRNA gene sequencing and phenotypic testing of eight related, but unidentified, isolates located in a historical collection at the Centers for Disease Control and Prevention suggested that these isolates belong to a novel genera of bacteria. The genomes of the bacteria, to be named Oblitimonas alkaphilia gen. nov. sp. nov., were sequenced using Illumina technology. Closed genomes were produced for all eight isolates. PMID- 26679586 TI - Draft Genome of the Arthrobacter sp. Strain Edens01. AB - We report the draft genome sequence of Arthrobacter sp. strain Edens01, isolated from a leaf surface of a Rosa hybrid plant as part of the Howard Hughes Medical Institute-funded Student Initiated Microbial Discovery (SIMD) project. The genome has a total size of 3,639,179 bp and contig N50 of 454,897 bp. PMID- 26679587 TI - Draft Genome Sequences of Six Pseudoalteromonas Strains, P1-7a, P1-9, P1-13-1a, P1-16-1b, P1-25, and P1-26, Which Induce Larval Settlement and Metamorphosis in Hydractinia echinata. AB - To gain a broader understanding of the importance of a surface-associated lifestyle and morphogenic capability, we have assembled and annotated the genome sequences of Pseudoalteromonas strains P1-7a, P1-9, P1-13-1a, P1-16-1b, P1-25, and P1-26, isolated from Hydractinia echinata. These genomes will allow detailed studies on bacterial factors mediating interkingdom communication. PMID- 26679588 TI - Genome Sequence of Acinetobacter baumannii Strain D36, an Antibiotic-Resistant Isolate from Lineage 2 of Global Clone 1. AB - Multiply antibiotic-resistant Acinetobacter baumannii isolate D36 was recovered in Australia in 2008 and belongs to a distinct lineage of global clone 1 (GC1). Here, we present the complete 4.13 Mbp genome sequence (chromosome plus 4 plasmids), generated via long read sequencing (PacBio). PMID- 26679589 TI - Next-Generation Whole-Genome Sequencing of Eight Strains of Bacillus cereus, Isolated from Food. AB - Bacillus cereus can contaminate food and cause emetic and diarrheal foodborne illness. Here, we report whole-genome sequences of eight strains of B. cereus, isolated from different food sources. PMID- 26679590 TI - Genome Sequence of Bradyrhizobium viridifuturi Strain SEMIA 690T, a Nitrogen Fixing Symbiont of Centrosema pubescens. AB - SEMIA 690(T) is a nitrogen-fixing symbiont of Centrosema pubescens, and comprises the recently described species Bradyrhizobium viridifuturi. Its draft genome indicates that it belongs to the Bradyrhizobium elkanii superclade. SEMIA 690(T) carries two copies of the regulatory nodD gene, and the nod and nif operons resemble those of Bradyrhizobium diazoefficiens. PMID- 26679591 TI - Genome Sequence of Bradyrhizobium tropiciagri Strain CNPSo 1112T, Isolated from a Root Nodule of Neonotonia wightii. AB - CNPSo 1112(T) is a nitrogen-fixing symbiont of perennial soybean, a tropical legume forage. Its draft genome indicates a large genome with a circular chromosome and 9,554 coding sequences (CDSs). Operons of nodulation, nitrogen fixation, and uptake hydrogenase were present in the symbiotic island, and the genome encompasses several CDSs of stress tolerance. PMID- 26679592 TI - Permanent Draft Genome Sequence of Frankia sp. Strain ACN1ag, a Nitrogen-Fixing Actinobacterium Isolated from the Root Nodules of Alnus glutinosa. AB - Frankia strain ACN1(ag) is a member of Frankia lineage Ia, which are able to re infect plants of the Betulaceae and Myricaceae families. Here, we report a 7.5 Mbp draft genome sequence with a G+C content of 72.35% and 5,687 candidate protein-encoding genes. PMID- 26679593 TI - Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant CH/HNYF/2014. AB - Sow's milk is a potential route for the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sow to suckling piglet. We report here the complete genome sequence of PEDV strain CH/HNYF/2014, which was isolated from milk samples : This information provides further understanding of the transmission mechanisms and genetic diversity of PEDV. PMID- 26679594 TI - Draft Genome Sequence of Francisella tularensis Strain 410108 from Tibet, China. AB - Francisella tularensis is the etiological agent of the potentially fatal disease tularemia. Here, we report the draft genome sequence of a virulent human isolate from Tibet, China in 1962, F. tularensis strain 410108, an intermediate-genotype strain of F. tularensis subsp. holarctica between biovar japonica and non japonica strains in the world. PMID- 26679595 TI - Draft Genome Sequence of Caloranaerobacter sp. TR13, an Anaerobic Thermophilic Bacterium Isolated from a Deep-Sea Hydrothermal Vent. AB - Here, we report the draft 2,261,881-bp genome sequence of Caloranaerobacter sp. TR13, isolated from a deep-sea hydrothermal vent on the East Pacific Rise. The sequence will be helpful for understanding the genetic and metabolic features, as well as potential biotechnological application in the genus Caloranaerobacter. PMID- 26679596 TI - Complete Genome Sequences of Two Listeria monocytogenes Serovars, 1/2a and 4b, Isolated from Dairy Products in Brazil. AB - Listeria monocytogenes is the foodborne pathogen responsible for a bacterial infection called listeriosis. Here, we present the whole-genome sequences of two L. monocytogenes serovars, 1/2a and 4b, which are considered the most prevalent in food processing plants and listeriosis outbreaks, respectively. PMID- 26679597 TI - Genomic Sequence of a Clinical Vancomycin-Resistant Reference Strain, Enterococcus faecalis ATCC 51299. AB - In this paper, we present a draft genome sequence of a quality control reference strain, Enterococcus faecalis ATCC 51299 (multilocus sequencing type [MLST] ST6), which is sensitive to teicoplanin but resistant to vancomycin. It is used in an agar screening test for streptomycin, gentamicin, and vancomycin resistance and the resistance marker vanB. PMID- 26679598 TI - Complete Genome Sequences of Two Shiga Toxin-Producing Escherichia coli Strains from Serotypes O119:H4 and O165:H25. AB - Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen. Here, we report complete whole-genome sequences for two STEC strains of serotypes O119:H4 and O165:H25 isolated from clinical cases in the United States. PMID- 26679599 TI - De Novo Genome Sequence of "Candidatus Liberibacter solanacearum" from a Single Potato Psyllid in California. AB - The draft genome sequence of "Candidatus Liberibacter solanacearum" strain RSTM from a potato psyllid (Bactericera cockerelli) in California is reported here. The RSTM strain has a genome size of 1,286,787 bp, a G+C content of 35.1%, 1,211 predicted open reading frames (ORFs), and 43 RNA genes. PMID- 26679600 TI - Microglia and astrocyte activation in the frontal cortex of rats with experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the human disease multiple sclerosis (MS), a demyelinating and neurodegenerative pathology of the central nervous system. Both diseases share physiopathological and clinical characteristics, mainly associated with a neuroinflammatory process that leads to a set of motor, sensory, and cognitive symptoms. In MS, gray matter atrophy is related to the emergence of cognitive deficits and contributes to clinical progression. In particular, injury and dysfunction in certain areas of the frontal cortex (FrCx) have been related to the development of cognitive impairments with high incidence, like central fatigue and executive dysfunction. In the present work we show the presence of region-specific microglia and astrocyte activation in the FrCx, during the first hours of acute EAE onset. It is accompanied by the production of the pro-inflammatory cytokines IL-6 and TNF alpha, in the absence of detectable leukocyte infiltration. These findings expand previous studies showing presynaptic neural dysfunction occurring at the FrCx and might contribute to the understanding of the mechanisms involved in the genesis and prevalence of common MS symptoms. PMID- 26679601 TI - Evaluation of shear bond strength of veneering ceramics and zirconia fabricated by the digital veneering method. AB - PURPOSE: The purpose of this study was to evaluate the shear bond strength (SBS) of veneering ceramic and zirconia fabricated by the digital veneering method. METHODS: A total of 50 specimens were fabricated, i.e., 10 specimens each for the metal-ceramic (control) group and the four zirconia groups. The zirconia groups comprised specimens fabricated by the digital veneering method, the heat pressing method, and hand layering method for two groups, respectively. Furthermore, the shear bond strength was measured with a universal testing machine (Model 3345, Instron, Canton, MA, USA) and statistically analyzed using one-way ANOVA set at a significance level of P<0.05. The corresponding mode of failure was determined from Scanning Electron Microscope (FESEM JSM 6701F, Jeol Ltd., Japan) observations. RESULTS: One-way analysis of variance (ANOVA) revealed that the metal-ceramic group had the highest SBS (43.62MPa), followed by the digital veneering method (28.29MPa), the heat pressing method (18.89MPa), and the layering method (18.65, 17.21MPa). The samples fabricated by digital veneering had a significantly higher SBS than the other zirconia samples (P<0.05). All of the samples exhibited mixed failure. CONCLUSIONS: Veneering ceramic with a zirconia core that was fabricated via the digital veneering method is believed to be effective in clinical use since, its shear bond strength is significantly higher than that resulting from the conventional method. PMID- 26679602 TI - Proliferation and osteo/odontogenic differentiation of stem cells from apical papilla regulated by Zinc fingers and homeoboxes 2: An in vitro study. AB - In the process of tooth root development, stem cells from the apical papilla (SCAPs) can differentiate into odontoblasts and form root dentin, however, molecules regulating SCAPs differentiation have not been elucidated. Zinc fingers and homeoboxes 2 (ZHX2) is a novel transcriptional inhibitor. It is reported to modulate the development of nerve cells, liver cells, B cells, red blood cells, and so on. However, the role of ZHX2 in tooth root development remains unclear. In this study, we explored the potential role of ZHX2 in the process of SCAPs differentiation. The results showed that overexpression of ZHX2 upregulated the expression of osteo/odontogenic related genes and ALP activity, inhibited the proliferation of SCAPs. Consistently, ZHX2 knockdown reduced SCAPs mineralization and promoted SCAPs proliferation. These results indicated that ZHX2 plays a critical role in the proliferation and osteo/odontogenic differentiation of SCAPs. PMID- 26679604 TI - Two c-Myc binding sites are crucial in upregulating the expression of human phospholipid scramblase 1 gene. AB - Human phospholipid scramblase 1 (hPLSCR1) is a type II endofacial membrane protein which mediates bi-directional transport of phospholipids across the plasma membrane. hPLSCR1, a multifunctional protein with variety of roles in apoptosis, tumor progression, cell signaling and anti-viral defense. The expression of such a multifunctional protein should be under tight regulation. Apart from a single report showing snail mediated down regulation of hPLSCR1, the molecular mechanisms regulating the expression of scramblases are not well elucidated. In this study we identified c-Myc as a transcriptional regulator of hPLSCR1. Transcription factor prediction tool ConSite predicted three binding sites for c-Myc. Reporter gene assays and western blot analysis revealed c-Myc mediated up regulation of hPLSCR1 expression. Deletion construct -790 lacking one c-Myc binding site showed a 27% decrease in promoter activity while deletion construct -469 lacking two c-Myc binding sites showed a 62% decrease in promoter activity. Site directed mutagenesis revealed the importance of c-Myc binding sites from -751 to -756 and -548 to -553 on the promoter of hPLSCR1in transcriptionally regulating the expression of hPLSCR1. The results were further confirmed by shRNA mediated knock down of endogenous c-Myc and in vivo interactions by ChIP assay. PMID- 26679603 TI - Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer. AB - Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize beta-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer. PMID- 26679605 TI - miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1. AB - MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G0/G1 arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3' untranslated region (3'-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease. PMID- 26679606 TI - Hepatic maturation of human iPS cell-derived hepatocyte-like cells by ATF5, c/EBPalpha, and PROX1 transduction. AB - Hepatocyte-like cells differentiated from human iPS cells (human iPS-HLCs) are expected to be utilized in drug development and research. However, recent hepatic characterization of human iPS-HLCs showed that these cells resemble fetal hepatocytes rather than adult hepatocytes. Therefore, in this study, we aimed to develop a method to enhance the hepatic function of human iPS-HLCs. Because the gene expression levels of the hepatic transcription factors (activating transcription factor 5 (ATF5), CCAAT/enhancer-binding protein alpha (c/EBPalpha), and prospero homeobox protein 1 (PROX1)) in adult liver were significantly higher than those in human iPS-HLCs and fetal liver, we expected that the hepatic functions of human iPS-HLCs could be enhanced by adenovirus (Ad) vector-mediated ATF5, c/EBPalpha, and PROX1 transduction. The gene expression levels of cytochrome P450 (CYP) 2C9, 2E1, alpha-1 antitrypsin, transthyretin, Na+/taurocholate cotransporting polypeptide, and uridine diphosphate glucuronosyl transferase 1A1 and protein expression levels of CYP2C9 and CYP2E1 were upregulated by ATF5, c/EBPalpha, and PROX1 transduction. These results suggest that the hepatic functions of the human iPS-HLCs could be enhanced by ATF5, c/EBPalpha, and PROX1 transduction. Our findings would be useful for the hepatic maturation of human iPS-HLCs. PMID- 26679607 TI - Phosphorylation-mediated regulation of the Staphylococcus aureus secreted tyrosine phosphatase PtpA. AB - Due to the emergence of methicillin-resistant strains, Staphylococcus aureus has become as major public-health threat. Studies aimed at deciphering the molecular mechanism of virulence are thus required to identify new targets and develop efficient therapeutic agents. Protein phosphorylations are known to play key regulatory functions and their roles in pathogenesis are under intense scrutiny. Here we analyzed the protein tyrosine phosphatase PtpA of S. aureus, a member of the family of low molecular weight protein tyrosine phosphatases that are often secreted by pathogenic bacteria. We report for the first time that PtpA is phosphorylated in vitro by the S. aureus tyrosine kinase CapA1B2. A mass spectrometry approach allowed determining that Tyr122 and Tyr123 were the only two residues phosphorylated by this kinase. This result was confirmed by analysis of a double PtpA_Y122A/Y123A mutant that showed no phosphorylation by CapA1B2. Interestingly, PtpA phosphatase activity was abrogated in this mutant, suggesting a key regulatory function for these two tyrosine residues. This was further reinforced by the observation that CapA1B2-mediated phosphorylation significantly increased PtpA phosphatase activity. Moreover, we provide evidence that PtpA is secreted during growth of S. aureus. Together our results suggest that PtpA is an exported S. aureus signaling molecule controlled by tyrosine phosphorylation which may interfere with host cell signaling. PMID- 26679608 TI - Complete mitochondrial genome of maritime striped squirrel Tamiops maritimus (Rodentia: Sciuridae). AB - The complete mitochondrial genome of the maritime striped squirrel (Tamiops maritimus) was first sequenced and characterized. The genome was 16 523 bp in length, and the composition and the arrangement of genes were analogous to other rodents. The sequence of T. maritimus was used to construct phylogenetic tree with additional mitochondrial genomes of seven sciurid species available on GenBank. Phylogenetic result indicated that T. maritimus has a close relationship with T. swinhoei. Our mitochondrial genome data may provide information for species identification, diversity evaluation, and other studies about this genus. PMID- 26679609 TI - Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function. AB - Hypoxic preconditioning is a promising strategy to prevent hypoxia-induced damages to several tissues. This effect is related to prior stabilization of the hypoxia-inducible factor-1alpha via inhibition of the prolyl-hydroxylases (PHDs), which are responsible for its degradation under normoxia. Although PHD inhibition has been shown to increase endurance performance in rodents, potential side effects of such a therapy have not been explored. Here, we investigated the effects of 1 wk of dimethyloxalylglycine (DMOG) treatment (150 mg/kg) on exercise capacity, as well as on cardiac and skeletal muscle function in sedentary and endurance-trained rats. DMOG improved maximal aerobic velocity and endurance in both sedentary and trained rats. This effect was associated with an increase in red blood cells without significant alteration of skeletal muscle contractile properties. In sedentary rats, DMOG treatment resulted in enhanced left ventricle (LV) weight together with impairment in diastolic function, LV relaxation, and pulse pressure. Moreover, DMOG decreased maximal oxygen uptake (state 3) of isolated mitochondria from skeletal muscle. Importantly, endurance training reversed the negative effects of DMOG treatment on cardiac function and restored maximal mitochondrial oxygen uptake to the level of sedentary placebo-treated rats. In conclusion, we provide here evidence that the PHD inhibitor DMOG has detrimental influence on myocardial and mitochondrial function in healthy rats. However, one may suppose that the deleterious influence of PHD inhibition would be potentiated in patients with already poor physical condition. Therefore, the present results prompt us to take into consideration the potential side effects of PHD inhibitors when administrated to patients. PMID- 26679611 TI - Regional specific modulation of the glycocalyx and smooth muscle cell contractile apparatus in conduit arteries of tail-suspended rats. AB - The glycocalyx is a key mechanosensor on the surfaces of vascular cells (endothelial cells and smooth muscle cells), and recently, we reported that the redistribution of the hemodynamic factors in tail-suspended (TS) hindlimb unloaded rats induces the dimensional adaptation of the endothelial glycocalyx in a regional-dependent manner. In the present study, we investigated the coverage and gene expression of the glycocalyx and its possible relationship with smooth muscle contractility in the conduit arteries from the TS rats. The coverage of the glycocalyx, determined by the area analysis of the fluorescein isothiocyanate labeled wheat germ agglutinin (WGA-FITC) staining to the cryosections of rat vessels, showed a 27.2% increase in the common carotid artery, a 13.3 and 8.0% decrease in the corresponding abdominal aorta and the femoral artery after 3 wk of tail suspension. The relative mRNA levels of syndecan-2, 3, 4, glypican-1, smooth muscle protein 22 (SM22), smoothelin (SMTN), and calponin were enhanced to 1.40, 1.53, 1.70, 1.90, 2.93, 2.30, and 5.23-fold, respectively, in the common carotid artery of the TS rat. However, both glycocalyx-related genes and smooth muscle contractile apparatus were totally or partially downregulated in the abdominal aorta and femoral artery of the TS rat. A linear positive correlation between the normalized coverage of glycocalyx and normalized mRNA levels of SM22, SMTN, and calponin exists. These results suggest the regional-dependent adaptation of the glycocalyx in simulated microgravity condition, which may affect its mechanotransduction of shear stress to regulate the contractility of the smooth muscle, finally contributing to postspaceflight orthostatic intolerance. PMID- 26679610 TI - Acupuncture plus low-frequency electrical stimulation (Acu-LFES) attenuates denervation-induced muscle atrophy. AB - Muscle wasting occurs in a variety of clinical situations, including denervation. There is no effective pharmacological treatment for muscle wasting. In this study, we used a tibial nerve denervation model to test acupuncture plus low frequency electric stimulation (Acu-LFES) as a therapeutic strategy for muscle atrophy. Acupuncture needles were connected to an SDZ-II electronic acupuncture device delivering pulses at 20 Hz and 1 mA; the treatment was 15 min daily for 2 wk. Acu-LFES prevented soleus and plantaris muscle weight loss and increased muscle cross-sectional area in denervated mice. The abundances of Pax7, MyoD, myogenin, and embryonic myosin heavy chain were significantly increased by Acu LFES in both normal and denervated muscle. The number of central nuclei was increased in Acu-LFES-treated muscle fibers. Phosphorylation of Akt was downregulated by denervation leading to a decline in muscle mass; however, Acu LFES prevented the denervation-induced decline largely by upregulation of the IGF 1 signaling pathway. Acu-LFES reduced the abundance of muscle catabolic proteins forkhead O transcription factor and myostatin, contributing to the attenuated muscle atrophy. Acu-LFES stimulated the expression of macrophage markers (F4/80, IL-1b, and arginase-1) and inflammatory cytokines (IL-6, IFNgamma, and TNFalpha) in normal and denervated muscle. Acu-LFES also stimulated production of the muscle-specific microRNAs miR-1 and miR-206. We conclude that Acu-LFES is effective in counteracting denervation-induced skeletal muscle atrophy and increasing muscle regeneration. Upregulation of IGF-1, downregulation of myostatin, and alteration of microRNAs contribute to the attenuation of muscle atrophy in denervated mice. PMID- 26679613 TI - Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular remodeling through HIF-1 activation. AB - Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1alpha gene (HIF-1alpha(+/-)) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-kappaB (NF-kappaB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-kappaB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1alpha(+/-) and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-kappaB. PMID- 26679612 TI - The regulation of autophagy during exercise in skeletal muscle. AB - The merits of exercise on muscle health and well-being are numerous and well documented. However, the mechanisms underlying the robust adaptations induced by exercise, particularly on mitochondria, are less clear and much sought after. Recently, an evolutionary conserved cellular recycling mechanism known as autophagy has been implicated in the adaptations to acute and chronic exercise. A basal level of autophagy is constantly ongoing in cells and tissues, ensuring cellular clearance and energy homeostasis. This pathway can be further induced, as a survival mechanism, by cellular perturbations, such as energetic imbalance and oxidative stress. During exercise, a biphasic autophagy response is mobilized, leading to both an acute induction and a long-term potentiation of the process. Posttranslational modifications arising from upstream signaling cascades induce an acute autophagic response during a single bout of exercise by mobilizing core autophagy machinery. A transcriptional program involving the regulators Forkhead box O, transcription factor EB, p53, and peroxisome proliferator coactivator-1alpha is also induced to fuel sustained increases in autophagic capacity. Autophagy has also been documented to mediate chronic exercise-induced metabolic benefits, and animal models in which autophagy is perturbed do not adapt to exercise to the same extent. In this review, we discuss recent developments in the field of autophagy and exercise. We specifically highlight the molecular mechanisms activated during acute exercise that lead to a prolonged adaptive response. PMID- 26679615 TI - Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead. AB - By its very nature, exercise exerts a challenge to the body's cellular homeostatic mechanisms. This homeostatic challenge affects not only the contracting skeletal muscle but also a number of other organs and results over time in exercise-induced adaptations. Thus it is no surprise that heat shock proteins (HSPs), a group of ancient and highly conserved cytoprotective proteins critical in the maintenance of protein and cellular homeostasis, have been implicated in exercise/activity-induced adaptations. It has become evident that HSPs such as HSP72 are induced or activated with acute exercise or after chronic exercise training regimens. These observations have given scientists an insight into the protective mechanisms of these proteins and provided an opportunity to exploit their protective role to improve health and physical performance. Although our knowledge in this area of physiology has improved dramatically, many questions still remain unanswered. Further understanding of the role of HSPs in exercise physiology may prove beneficial for therapeutic targeting in diseased patient cohorts, exercise prescription for disease prevention, and training strategies for elite athletes. PMID- 26679614 TI - Influence of muscle metabolic heterogeneity in determining the Vo2p kinetic response to ramp-incremental exercise. AB - The pulmonary O2 uptake (Vo2p) response to ramp-incremental (RI) exercise increases linearly with work rate (WR) after an early exponential phase, implying that a single time constant (tau) and gain (G) describe the response. However, variability in tau and G of Vo2p kinetics to different step increments in WR is documented. We hypothesized that the "linear" Vo2p-WR relationship during RI exercise results from the conflation between WR-dependent changes in tau and G. Nine men performed three or four repeats of RI exercise (30 W/min) and two step incremental protocols consisting of four 60-W increments beginning from 20 W or 50 W. During testing, breath-by-breath Vo2p was measured by mass spectrometry and volume turbine. For each individual, the Vo2p RI response was characterized with exponential functions containing either constant or variable tau and G values. A relationship between tau and G vs. WR was determined from the step-incremental protocols to derive the variable model parameters. tau and G increased from 21 +/ 5 to 98 +/- 20 s and from 8.7 +/- 0.6 to 12.0 +/- 1.9 ml.min(-1).W(-1) for WRs of 20-230 W, respectively, and were best described by a second-order (tau) and a first-order (G) polynomial function of WR (lowest Akaike information criterion score). The sum of squared residuals was not different (P > 0.05) when the Vo2p RI response was characterized with either the constant or variable models, indicating that they described the response equally well. Results suggest that tau and G increase progressively with WR during RI exercise. Importantly, these relationships may conflate to produce a linear Vo2p-WR response, emphasizing the influence of metabolic heterogeneity in determining the apparent Vo2p-WR relationship during RI exercise. PMID- 26679616 TI - The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers. AB - Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect. PMID- 26679617 TI - Energy expenditure during level human walking: seeking a simple and accurate predictive solution. AB - Accurate prediction of the metabolic energy that walking requires can inform numerous health, bodily status, and fitness outcomes. We adopted a two-step approach to identifying a concise, generalized equation for predicting level human walking metabolism. Using literature-aggregated values we compared 1) the predictive accuracy of three literature equations: American College of Sports Medicine (ACSM), Pandolf et al., and Height-Weight-Speed (HWS); and 2) the goodness-of-fit possible from one- vs. two-component descriptions of walking metabolism. Literature metabolic rate values (n = 127; speed range = 0.4 to 1.9 m/s) were aggregated from 25 subject populations (n = 5-42) whose means spanned a 1.8-fold range of heights and a 4.2-fold range of weights. Population-specific resting metabolic rates (Vo2 rest) were determined using standardized equations. Our first finding was that the ACSM and Pandolf et al. equations underpredicted nearly all 127 literature-aggregated values. Consequently, their standard errors of estimate (SEE) were nearly four times greater than those of the HWS equation (4.51 and 4.39 vs. 1.13 ml O2.kg(-1).min(-1), respectively). For our second comparison, empirical best-fit relationships for walking metabolism were derived from the data set in one- and two-component forms for three Vo2-speed model types: linear (?V(1.0)), exponential (?V(2.0)), and exponential/height (?V(2.0)/Ht). We found that the proportion of variance (R(2)) accounted for, when averaged across the three model types, was substantially lower for one- vs. two component versions (0.63 +/- 0.1 vs. 0.90 +/- 0.03) and the predictive errors were nearly twice as great (SEE = 2.22 vs. 1.21 ml O2.kg(-1).min(-1)). Our final analysis identified the following concise, generalized equation for predicting level human walking metabolism: Vo2 total = Vo2 rest + 3.85 + 5.97.V(2)/Ht (where V is measured in m/s, Ht in meters, and Vo2 in ml O2.kg(-1).min(-1)). PMID- 26679619 TI - Effect of hypoxia-inducible factors in normal and leukemic stem cell regulation and their potential therapeutic impact. AB - INTRODUCTION: Hypoxia inducible factors (HIF-1alpha and HIF-2alpha) are the main mediators of hypoxic responses that operate in both normal and pathological conditions. Recent evidence indicates that HIF-1alpha and HIF-2alpha could have overlapping, unique and even sometimes opposing activities in both normal physiology and disease. Despite an increase in our understanding of the different pathways regulated by HIF-1alpha and HIF-2alpha, the role played by each factor in HSC maintenance and leukemogenesis is still controversial. AREAS COVERED: This review summarizes our current understanding of HIF-1alpha and HIF-2alpha activities and discusses the implications and challenges of using HIF inhibitors therapeutically in blood malignancies. EXPERT OPINION: As HIF inhibitors are currently under clinical evaluation in different cancers, including hematological malignancies, a more thorough understanding of the unique roles performed by HIF 1alpha and HIF-2alpha in human neoplasia is warranted. PMID- 26679618 TI - Central nervous system integration of sensorimotor signals in oral and pharyngeal structures: oropharyngeal kinematics response to recurrent laryngeal nerve lesion. AB - Safe, efficient liquid feeding in infant mammals requires the central coordination of oropharyngeal structures innervated by multiple cranial and spinal nerves. The importance of laryngeal sensation and central sensorimotor integration in this system is poorly understood. Recurrent laryngeal nerve lesion (RLN) results in increased aspiration, though the mechanism for this is unclear. This study aimed to determine the effect of unilateral RLN lesion on the motor coordination of infant liquid feeding. We hypothesized that 1) RLN lesion results in modified swallow kinematics, 2) postlesion oropharyngeal kinematics of unsafe swallows differ from those of safe swallows, and 3) nonswallowing phases of the feeding cycle show changed kinematics postlesion. We implanted radio opaque markers in infant pigs and filmed them pre- and postlesion with high-speed videofluoroscopy. Markers locations were digitized, and swallows were assessed for airway protection. RLN lesion resulted in modified kinematics of the tongue relative to the epiglottis in safe swallows. In lesioned animals, safe swallow kinematics differed from unsafe swallows. Unsafe swallow postlesion kinematics resembled prelesion safe swallows. The movement of the tongue was reduced in oral transport postlesion. Between different regions of the tongue, response to lesion was similar, and relative timing within the tongue was unchanged. RLN lesion has a pervasive effect on infant feeding kinematics, related to the efficiency of airway protection. The timing of tongue and hyolaryngeal kinematics in swallows is a crucial locus for swallow disruption. Laryngeal sensation is essential for the central coordination in feeding of oropharyngeal structures receiving motor inputs from different cranial nerves. PMID- 26679620 TI - Steric hindrance regulated supramolecular assembly between beta-cyclodextrin polymer and pyrene for alkaline phosphatase fluorescent sensing. AB - We herein report a strategy for sensitive alkaline phosphatase (ALP) fluorescent sensing based on steric hindrance regulated supramolecular assembly between beta cyclodextrin polymer (polybeta-CD) and pyrene. The fluorescence of pyrene was enhanced more than 10 times through supramolecular assembly with polybeta-CD. The 5'-phosphorylated dsDNA probe with pyrene attached on the 3'-terminal could be cleaved by lambda exonuclease (lambda exo), yielding pyrene attached on mononucleotides. Pyrene attached on mononucleotides could easily enter the cavity of polybeta-CD, resulting in fluorescence enhancement. When ALP was introduced, it could remove 5'-phosphate groups from dsDNA and then prevented the cleavage of dsDNA. Pyrene attached on dsDNA was difficult to enter the cavity of polybeta-CD because of steric hindrance, resulting in an inconspicuous fluorescence enhancement. Owing to the excellent fluorescence enhancement during steric hindrance regulated supramolecular assembly, excellent performance of the assay method was achieved for ALP with a detection limit of 0.04 Um L(-1). The detection limit was superior or comparable with the reported methods. Besides, this method was simple in design, avoiding double-labeling of probe. PMID- 26679622 TI - Dilemmas in Managing Pregnant Women With Ebola: 2 Case Reports. AB - We report 2 cases of Ebola viral disease (EVD) in pregnant women who survived, initially with intact pregnancies. Respectively 31-32 days after negativation of the maternal blood EVD-polymerase chain reaction (PCR) both patients delivered a stillborn fetus with persistent EVD-PCR amniotic fluid positivity. PMID- 26679623 TI - Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea. AB - BACKGROUND: Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. METHODS: We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. RESULTS: Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients' respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. CONCLUSIONS: Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms. PMID- 26679624 TI - Travel Destinations and Sexual Behavior as Indicators of Antibiotic Resistant Shigella Strains--Victoria, Australia. AB - BACKGROUND: Knowledge of relationships between antibiotic susceptibility of Shigella isolates and travel destination or other risk factors can assist clinicians in determining appropriate antibiotic therapy prior to susceptibility testing. We describe relationships between resistance patterns and risk factors for acquisition in Shigella isolates using routinely collected data for notified cases of shigellosis between 2008 and 2012 in Victoria, Australia. METHODS: We included all shigellosis patients notified during the study period, where Shigella isolates were tested for antimicrobial sensitivity using Clinical and Laboratory Standards Institute breakpoints. Cases were interviewed to collect data on risk factors, including recent travel. Data were analyzed using Stata 13.1 to examine associations between risk factors and resistant strains. RESULTS: Of the 500 cases of shigellosis, 249 were associated with overseas travel and 210 were locally acquired. Forty-six of 51 isolates of Indian origin displayed decreased susceptibility or resistance to ciprofloxacin. All isolates of Indonesian origin were susceptible to ciprofloxacin. Twenty-six travel-related isolates were resistant to all tested oral antimicrobials. Male-to-male sexual contact was the primary risk factor for 80% (120/150) of locally acquired infections among adult males, characterized by distinct periodic Shigella sonnei outbreaks. CONCLUSIONS: Clinicians should consider travel destination as a marker for resistance to common antimicrobials in returning travelers, where severe disease requires empirical treatment prior to receipt of individual sensitivity testing results. Repeated outbreaks of locally acquired shigellosis among men who have sex with men highlight the importance of prevention and control measures in this high-risk group. PMID- 26679625 TI - Retention in Care and Patient-Reported Reasons for Undocumented Transfer or Stopping Care Among HIV-Infected Patients on Antiretroviral Therapy in Eastern Africa: Application of a Sampling-Based Approach. AB - BACKGROUND: Improving the implementation of the global response to human immunodeficiency virus requires understanding retention after starting antiretroviral therapy (ART), but loss to follow-up undermines assessment of the magnitude of and reasons for stopping care. METHODS: We evaluated adults starting ART over 2.5 years in 14 clinics in Uganda, Tanzania, and Kenya. We traced a random sample of patients lost to follow-up and incorporated updated information in weighted competing risks estimates of retention. Reasons for nonreturn were surveyed. RESULTS: Among 18 081 patients, 3150 (18%) were lost to follow-up and 579 (18%) were traced. Of 497 (86%) with ascertained vital status, 340 (69%) were alive and, in 278 (82%) cases, updated care status was obtained. Among all patients initiating ART, weighted estimates incorporating tracing outcomes found that 2 years after ART, 69% were in care at their original clinic, 14% transferred (4% official and 10% unofficial), 6% were alive but out of care, 6% died in care (<60 days after last visit), and 6% died out of care (>= 60 days after last visit). Among lost patients found in care elsewhere, structural barriers (eg, transportation) were most prevalent (65%), followed by clinic-based (eg, waiting times) (33%) and psychosocial (eg, stigma) (27%). Among patients not in care elsewhere, psychosocial barriers were most prevalent (76%), followed by structural (51%) and clinic based (15%). CONCLUSIONS: Accounting for outcomes among those lost to follow-up yields a more informative assessment of retention. Structural barriers contribute most to silent transfers, whereas psychological and social barriers tend to result in longer-term care discontinuation. PMID- 26679626 TI - Use of the Novel Therapeutic Agent Miltefosine for the Treatment of Primary Amebic Meningoencephalitis: Report of 1 Fatal and 1 Surviving Case. AB - Primary amebic meningoencephalitis (PAM) is a fulminant central nervous system infection caused by the thermophilic free-living ameba Naegleria fowleri. Few survivals have been documented and adequate treatment is lacking. We report 2 PAM cases, 1 fatal and 1 surviving, treated with the novel antiparasitic agent miltefosine. PMID- 26679627 TI - Can We Better Optimize Vancomycin Monotherapy? PMID- 26679629 TI - Esophagogastric junction distensibility measurements during hydraulic dilation therapy in achalasia patients. AB - Increasing evidence suggests that esophagogastric junction (EGJ) distensibility is predictive of long-term clinical success after achalasia treatment. A new commercially available hydraulic dilation balloon is capable of measuring EGJ opening diameters whilst simultaneously dilating the EGJ. Deployed alongside the endoscope under direct visualization, it is used for dilation of the lower esophageal sphincter in patients with achalasia. Impedance measurement electrodes are incorporated in the catheter shaft in the dilation balloon, which allows measuring the diameter of the EGJ and displaying it in real time before, during and after dilation. This obviates the need for fluoroscopy during the dilation procedure. The extent of recoil of the EGJ after dilation potentially provides a measurement that could be incorporated into a clinical rule for predicting therapeutic success after dilation. PMID- 26679630 TI - Fish oil regulates blood fatty acid composition and oxylipin levels in healthy humans: A comparison of young and older men. AB - SCOPE: Increased consumption of fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with improved cardiometabolic health and inflammatory status; however, age-related responses remain poorly described. METHODS AND RESULTS: In a placebo-controlled study, healthy young and older men consumed five fish oil capsules daily, providing 2.0 g/d EPA and 1.0g/d DHA, for three months. Both young and older men experienced a ~30% reduction in blood triglycerides with fish oil supplementation. A significant group * time interaction was observed for DHA, with young men experiencing a ~twofold increase in DHA in serum and RBCs, while older men showed negligible increases. Other fatty acids were differentially regulated between young and older men, most notably osbond acid and several saturates. Small changes were observed in serum oxylipins, with both groups of men responding similarly: 5-HETE was reduced, while PGF2alpha and 17-HDoHE were increased. Changes in oxylipins occurred independent of changes in whole blood expression of key genes regulating oxylipin production. CONCLUSION: Our study suggests that both young and older men experience the triglyceride-lowering benefits associated with fish oil supplements, but show differential responses in blood fatty acids. Additionally, fish oil promotes an improved oxylipin profile in both groups of men. PMID- 26679631 TI - CTLA-4 blockade in the treatment of rheumatoid arthritis: an update. AB - Rheumatoid arthritis (RA) is characterized by chronic joint inflammation as well as by extra-articular involvement. The immunopathology of RA is polygenic and involves different cell populations. Patients with an inadequate response to non biologic disease- modifying antirheumatic drugs (DMARDs) should integrate their therapy with biologic DMARDs. Biologic DMARDs can target several inflammatory cytokines, or CD20+ B cells, or can modulate T-cell co-stimulation and activation. The cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4-Ig: abatacept) that selectively modulates the CD28:CD80/86 co stimulation signal appears a biologic DMARD interacting with T cells but also with other cell populations involved in RA pathophysiology. Activated B lymphocytes, macrophages, osteoclasts and endothelial cells express the costimulatory molecules (CD80/86) and are downregulated by CTLA-4 blockade. The relatively low frequency and severity of safety issues related to CTLA-4-Ig treatment seems further to confirm the targeted downregulatory action exerted by the fusion protein, which is mainly focussed on activated immune/inflammatory cells. PMID- 26679632 TI - Modeling Bacterial Infection Phenomena. AB - A series of cellular automata models of bacteria were created, where encounters with models of the immune system and a model of an antibiotic drug were present. The dose of the antibiotic, its potency and the timeliness of its administration were variables. The emergence of antibiotic resistance by the bacteria was an outcome associated with the administration of the drug. The models created in these studies were found to closely relate to clinical experiences, making the general model useful for further simulation studies. PMID- 26679633 TI - Soil transference patterns on bras: Image processing and laboratory dragging experiments. AB - In a recent Australian homicide, trace soil on the victim's clothing suggested she was initially attacked in her front yard and not the park where her body was buried. However the important issue that emerged during the trial was how soil was transferred to her clothing. This became the catalyst for designing a range of soil transference experiments (STEs) to study, recognise and classify soil patterns transferred onto fabric when a body is dragged across a soil surface. Soil deposits of interest in this murder were on the victim's bra and this paper reports the results of anthropogenic soil transfer to bra-cups and straps caused by dragging. Transfer patterns were recorded by digital photography and photomicroscopy. Eight soil transfer patterns on fabric, specific to dragging as the transfer method, appeared consistently throughout the STEs. The distinctive soil patterns were largely dependent on a wide range of soil features that were measured and identified for each soil tested using X-ray Diffraction and Non Dispersive Infra-Red analysis. Digital photographs of soil transfer patterns on fabric were analysed using image processing software to provide a soil object oriented classification of all soil objects with a diameter of 2 pixels and above transferred. Although soil transfer patterns were easily identifiable by naked eye alone, image processing software provided objective numerical data to support this traditional (but subjective) interpretation. Image software soil colour analysis assigned a range of Munsell colours to identify and compare trace soil on fabric to other trace soil evidence from the same location; without requiring a spectrophotometer. Trace soil from the same location was identified by linking soils with similar dominant and sub-dominant Munsell colour peaks. Image processing numerical data on the quantity of soil transferred to fabric, enabled a relationship to be discovered between soil type, clay mineralogy (smectite), particle size and soil moisture content that would not have been possible otherwise. Soil type (e.g. Anthropogenic, gravelly sandy loam soil or Natural, organic-rich soil), clay mineralogy (smectite) and soil moisture content were the greatest influencing factors in all the dragging soil transference tests (both naked eye and measured properties) to explain the eight categories of soil transference patterns recorded. This study was intended to develop a method for dragging soil transference laboratory experiments and create a baseline of preliminary soil type/property knowledge. Results confirm the need to better understand soil behaviour and properties of clothing fabrics by further testing of a wider range of soil types and clay mineral properties. PMID- 26679634 TI - Assessment of higher level cognitive-communication functions in adolescents with ABI: Standardization of the student version of the functional assessment of verbal reasoning and executive strategies (S-FAVRES). AB - BACKGROUND: Childhood acquired brain injuries can disrupt communication functions needed for success in school, work and social interaction. Cognitive communication difficulties may not be apparent until adolescence, when academic, environmental and social-emotional demands increase. OBJECTIVE: The Functional Assessment of Verbal Reasoning and Executive Strategies for Students (S-FAVRES) is a new activity-level measure of cognitive-communication skills in complex, contextual and integrative tasks that simulate real world communication challenges. It is hypothesized that S-FAVRES performance would differentiate adolescents with and without acquired brain injury (ABI) on scores for Accuracy, Rationale, Reasoning Subskills and Time. METHODS: S-FAVRES was administered to 182 typically-developing (TD) and 57 adolescents with mild-to-severe ABI aged 12 19. Group differences, internal consistency, sensitivity, specificity, reliability and contributing factors to performance (age, gender, brain injury) were examined statistically. RESULTS: Those with ABI attained statistically lower Accuracy, Rationale and Reasoning sub-skills scores than their TD peers. Time scores were not significantly different. Performance trends were consistent across tasks, administrations, gender and age groups. Inter-rater reliability for scoring was acceptable. CONCLUSION: The S-FAVRES provides a reliable, functional and quantifiable measure of subtle cognitive-communication difficulties in adolescents that can assist speech-language pathologists in planning treatment and integration to school and real world communication. PMID- 26679635 TI - Differentiation of Urine-Derived Human Induced Pluripotent Stem Cells to Alveolar Type II Epithelial Cells. AB - Human alveolar type II (AT II) epithelial cells are valuable for the cellular therapy of lung disease. Human induced pluripotent stem cells (iPSCs) have the ability to generate AT II cells that can be used in modeling and treatment of lung disease caused by dysfunction of AT II cells. In this study, we present a simple, effective, and noninvasive way of obtaining human iPSCs from exfoliated renal epithelial cells, which exist in urine. Alkaline phosphatase (AP) staining, immunofluorescence staining, karyotyping, and teratoma experiments have proved that these iPSCs are pluripotent. Urinary iPSCs (UiPSCs) can differentiate into AT II cells with our four-step induction protocol. These cells have phenotypic properties similar to mature human AT II cells, such as outstretched and epithelium-like morphology and the specific expression markers of AT II cells (surfactant proteins A, B, and C). This study indicates that AT II cells can be generated from UiPSCs and these cells may be useful for the study of human lung development and regenerative medicine. PMID- 26679636 TI - Studying the lay of the land: views and experiences of professionals in the translational pluripotent stem cell field. AB - AIM: The inherent uncertainty of first-in-human trials, combined with the technical complexity of pluripotent stem cells (PSCs), makes early phase PSC studies ethically challenging. Conducting parallel bioethics research based on experiences and views of professionals in the stem cell field is therefore important. MATERIALS & METHODS: We conducted semistructured interviews with various stakeholders to get a lay of the land of ethical issues professionals find relevant to the translation of PSCs. RESULTS: We identified four themes in the interviews: the uniqueness of PSCs, the suitability of the current research paradigm, the justification for early phase PSC studies and the involvement of patients and research participants. CONCLUSION: We conclude that a debate should take place discussing the suitability of the current research paradigm for translational PSC studies. PMID- 26679637 TI - Genome-wide transcriptomic analyses provide insights into the lifestyle transition and effector repertoire of Leptosphaeria maculans during the colonization of Brassica napus seedlings. AB - Molecular interaction between the causal agent of blackleg disease, Leptosphaeria maculans (Lm), and its host, Brassica napus, is largely unknown. We applied a deep RNA-sequencing approach to gain insight into the pathogenicity mechanisms of Lm and the defence response of B. napus. RNA from the infected susceptible B. napus cultivar Topas DH16516, sampled at 2-day intervals (0-8 days), was sequenced and used for gene expression profiling. Patterns of gene expression regulation in B. napus showed multifaceted defence responses evident by the differential expression of genes encoding the pattern recognition receptor CERK1 (chitin elicitor receptor kinase 1), receptor like proteins and WRKY transcription factors. The up-regulation of genes related to salicylic acid and jasmonic acid at the initial and late stages of infection, respectively, provided evidence for the biotrophic and necrotrophic life stages of Lm during the infection of B. napus cotyledons. Lm transition from biotrophy to necrotropy was also supported by the expression function of Lm necrosis and ethylene-inducing (Nep-1)-like peptide. Genes encoding polyketide synthases and non-ribosomal peptide synthetases, with potential roles in pathogenicity, were up-regulated at 6-8 days after inoculation. Among other plant defence-related genes differentially regulated in response to Lm infection were genes involved in the reinforcement of the cell wall and the production of glucosinolates. Dual RNA sequencing allowed us to define the Lm candidate effectors expressed during the infection of B. napus. Several candidate effectors suppressed Bax-induced cell death when transiently expressed in Nicotiana benthamaina leaves. PMID- 26679638 TI - Association analysis between HFM1 variation and primary ovarian insufficiency in Chinese women. AB - HFM1 is a meiosis-specific gene and expressed in germ-line tissues. More recently, evidence has indicated that variations in HFM1 gene could be causative for primary ovarian insufficiency (POI), also known as premature ovarian failure. The aim of this study was to investigate the association between HFM1 gene variants and sporadic POI in Chinese women. A total of 138 POI patients and 316 healthy controls (matched for ethnic background, sex, and age of the patients) were recruited in this study. We screened the entire HFM1 coding region by direct sequencing in all subjects and identified six variants of HFM1 gene in POI group, namely c.148G>A/p.Glu50Lys, c.1241A>C/p.His414Pro, c.2325C>A/p.Phe775Leu, c.3367T>C/p.Ser1123Pro, c.3580C>T/p.Arg1194Cys, and c.1686-1G>C. The variation rate of HFM1 in POI group is significantly higher than control group (p < 0.01). The p.His414Pro and p.Arg1194Cys were predicted to be probably damaging to the HFM1 protein function, while p.Glu50Lys, p.Phe775Leu and p.Ser1123Pro mutants might not have any deleterious effect on the structure or function of the protein by online predictors. Taken together, our data suggested that HFM1 gene might be associated with primary ovarian insufficiency in Chinese population. PMID- 26679646 TI - [14-3-3/HIP-55 complex increases the stability of HIP-55]. AB - OBJECTIVE: To further demonstrate the interaction of a new 14-3-3 interaction protein hematopoietic progenitor kinase 1[HPK1]-interacting protein (HIP-55) and 14-3-3 proteins and its potential biological function in HEK293 cells. METHODS: PDEST-N-Venus-HIP-55WT (wild type),PDEST-N-Venus-HIP-55AA (mutants, S269A/T291A, abolishing the binding of HIP-55 to 14-3-3),PDEST-GST-HIP-55WT and PDEST-C-Venus 14-3-3tau plasmids were constructed by gateway system. Their expressions were demonstrated by Western blotting method. Then we used Bimolecular Fluorescence Complementation (BiFC) and co-immunoprecipitation (co-IP) methods to demonstrate the interaction of HIP-55 and 14-3-3 in HEK293 cells. Moreover, the 14-3-3 antagonist peptide, R18 and HIP-55 protein mutant plasmid HIP-55AA were used to detect the protein synthesis of HIP-55 at different time points induced by puromycin, an inhibitor of protein production. RESULTS: The HEK293 cells expressed HIP-55 protein respectively, after being transected with PDEST-N-Venus HIP-55WT,PDEST-N-Venus-HIP-55AA,PDEST-GST-HIP-55WT plasmids and expressed 14-3-3 protein after being transected with PDEST-C-Venus-14-3-3tau plasmids. We could detect venus fluorescence of venus-HIP-55 protein via confocal microscopy in HEK 293 cells transfected with N-Venus-HIP-55 and C-14-3-3tau plasmids by BiFC, but not in HEK 293 cells transfected with N-Venus-HIP-55 AA (mutants S269A/T291A) and C-14-3-3tau plasmids. The results of BiFC suggested that 14-3-3 interacted with HIP-55 through HIP-55 S269/T291 sites. At the same time, the data of co-IP showed that there were endogenous interactions between 14-3-3 and HIP-55. Furthermore, puromycin had no influence in HIP-55 protein synthesis at hours 0, 4, or 8 in HEK 293 cells expressing GST-HIP-55WT and 14-3-3 plasmids, while puromycin blocked HIP-55 protein synthesis in HEK 293 cells transfected with N-Venus-HIP-55AA (mutants S269A/T291A) and C-14-3-3tau plasmids. The results indicated that the 14 3-3/HIP-55 complex could contributed to the stability of HIP-55. CONCLUSION: HIP 55 forms a complex with 14-3-3 and 14-3-3/HIP-55 interaction increases the stability of HIP-55. PMID- 26679647 TI - [Dynamic alteration of CD154/CD40 and its effects on Th1/Th2 polarization in inducible co-stimulator ligand knockout mice infected with Schistosoma japonicum]. AB - OBJECTIVE: To analyze effect on the CD154-CD40 signaling pathway and Th1/Th2 polarization by deficient inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signaling in mice infected with Schistosoma japonicum. METHODS: ICOSL knockout (ICOSL-KO) mice and wild-type C57BL/6J mice were used as experimental Schistosomiasis model infected with Schistosoma japonicum. The expressions of CD154 and CD40 on splenocytes and on inflammatory cells around granulomatous infiltration of liver in mice infected with Schistosoma japonicum were analyzed by flow cytometry,immunohistochemical staining, respectively, on the day before infection (0 week)and at the end of 4, 7, 12, 16 and 20 weeks post-infection. The splenocytes of the mice were stimulated with soluble egg antigen(SEA) for 72 hours, then the concentrations of interferon gamma(IFN-gamma) and interleukin-4 (IL-4) in the culture supernatants were measured by sandwich enzyme-linked immunosorbent assay (ELISA) kits. The levels of SEA-specific antibodies of IgG and IgG1 and IgG2a were measured in the mice sera by ELISA. The granulomatous pathology in the mice liver was dynamically observed by hematoxylin and eosin (HE) staining. RESULTS: Compared with the wild-type C57BL/6J mice, the expressions of CD154 on CD4+ T splenocytes [(18.62 +/- 4.76)% vs.(27.91 +/- 3.94)%, (22.44 +/- 4.67)% vs.(40.86 +/- 5.21)%, (25.50 +/- 6.81)% vs.(43.81 +/- 8.41)%, (20.22 +/- 5.28)% vs.(40.95 +/- 7.34)%, (17.87 +/- 4.59)% vs.(33.16 +/- 6.31)%, all P<0.01] and of CD40 on CD19+ B splenocytes [(19.43 +/- 3.26)% vs.(24.37 +/- 3.59)%, (23.00 +/- 4.47)% vs.(31.80 +/- 5.86)%, (24.46 +/- 5.01)% vs.(35.85 +/- 5.32)%, (23.42 +/- 4.69)% vs.(33.30 +/- 6.14)%, (22.85 +/- 3.78)% vs.(30.88 +/- 5.94)%, all P<0.05] in the ICOSL-KO mice significantly decreased at the end of 4, 7, 12, 16 and 20 weeks post-infection. Moreover, the expressions of CD154[(0.319 +/- 0.066) vs.(0.488 +/- 0.086), (0.389 +/- 0.067) vs.(0.596 +/- 0.082), (0.378 +/- 0.064) vs.(0.543 +/- 0.072), (0.348 +/- 0.069) vs.(0.523 +/- 0.076), all P<0.01] and CD40[ (0.398 +/- 0.066) vs.(0.546 +/- 0.079), (0.461 +/- 0.085) vs.(0.618 +/- 0.076), (0.453 +/- 0.087) vs.(0.587 +/- 0.074), (0.449 +/- 0.065) vs.(0.565 +/- 0.082), all P<0.05] on inflammatory cells around granulomatous infiltration in liver from the ICOSL-KO mice were significantly lower than those of the wild-type C57BL/6J mice at the end of 7, 12, 16 and 20 weeks post-infection. The levels of IFN-gamma of the ICOSL-KO mice were significantly higher than those of the wild-type C57BL/6J mice at the end of 4, 7, 12, 16 and 20 weeks post-infection (P<0.05). However, the levels of IL-4 of the ICOSL-KO mice were significantly lower than those of the wild-type mice (P<0.05). Compared with the wild-type C57BL/6J mice, the levels of SEA-specific antibodies of IgG and IgG1 and IgG2a in the sera of the ICOSL-KO mice significantly decreased (P<0.01). Moreover, The Th2 differentiation index of the ICOSL-KO mice was significantly lower than that of the wild-type mice in post infection (P<0.01). Also, the ratio of IgG1/IgG2a of the ICOSL-KO mice were significantly lower than that of the wild-type mice at the end of 7, 12 and 16 weeks post-infection (P<0.05). And the volume of liver egg granulomas of the ICOSL-KO mice was significantly smaller than that of the wild-type mice (P<0.01). CONCLUSION: These findings suggest that there is obvious down-regulation in the expressions of CD154 and CD40 and impairment of Th2 immune response in the ICOSL KO mice infected with Schistosoma japonicum, accompanying with notedly reduced hepatic granulomatous pathology. The ICOS-ICOSL signaling has a regulatory effect on CD154-CD40 signaling pathway, and may play an important role in the hepatic egg granuloma formation of Schistosomiasis. PMID- 26679648 TI - [Association between CMTM5 gene rs723840 single nucleotide polymorphism and high on asprin platelet reactivity]. AB - OBJECTIVE: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR). METHODS: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and >= 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene. RESULTS: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264 0.947). CONCLUSION: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity. PMID- 26679649 TI - [Variation tendency in serum high density lipoprotein cholesterol and apolipoprotein A-I in different thyroid function status during pregnancy]. AB - OBJECTIVE: To study the metabolism of high density lipoprotein cholesterol (HDL C) and apolipoprotein A-I (ApoA-I) in different thyroid function status during pregnancy. METHODS: This study recruited thirty cases of euthyroid, with nineteen cases of subclinical hypothyroid and eight cases of subclinical hyperthyroid pregnancy. The concentrations of fasting serum HDL-C and ApoA-I were detected and analyzed from 9-12, 14-17, 23-26, and 37-40 gestational weeks. Friedman repeated measures ANOVA on ranks was adopted to analyze the changes of serum HDL-C and ApoA-I at different stages. General linear model (GLM) was adopted to analyze the differences of serum HDL-C and ApoA-I in different thyroid function status during pregnancy. RESULTS: There were no significant differences of maternal serum HDL-C among different stages (chi2 = 5.428,P=0.143, chi2 = 2.027,P=0.567, chi2 = 2.885,P=0.410). There were significant differences of serum ApoA-I during euthyroid and subclinical hypothyroid pregnancies (chi2 = 46.343, P<0.001, chi2 = 35.984, P<0.001), and no significant difference during subclinical hyperthyroid pregnancy (chi2 = 6.750, P=0.080). There were significant differences of serum HDL-C and ApoA-I between euthyroid and subclinical hyperthyroid pregnancies (P=0.025,P=0.027), and no significant differences between euthyroid and subclinical hypothyroid pregnancies (P=0.378,P=0.549). CONCLUSION: Subclinical hyperthyroidism affected the metabolism of maternal serum HDL-C and ApoA-I, which could affect the fetal growth and development. Subclinical hypothyroidism (after treatment with drugs) had no obvious effect on the metabolism of maternal serum HDL-C and ApoA-I. PMID- 26679628 TI - Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. AB - It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. PMID- 26679650 TI - [Distribution in different Salmonella serovars and integration sites of Salmonella paratyphi C phage SPC-P1]. AB - OBJECTIVE: To determine the prevalence of Salmonella paratyphi C phage (SPC-P1) in different Salmonella serovars and to identify the integration sites in host genome. METHODS: Based on the complete genome of SPC-P1 in S. paratyphi C RKS4594, 6 pairs of primers were designed and used to amplify the fragments of SPC-P1 in 11 S. typhi, 11 S. paratyphi A, 12 S. paratyphi B and 23 S. paratyphi C strains. At the same time, 100 complete genomes of Salmonella including 20 serovars available in National Center for Biotechnology Information (NCBI) database were downloaded and aligned by Mauve 2.3.1 to determine the prevalence of SPC-P1 in these serovars. Primers were designed according to the integration sites of SPC-P1 in the genome of RKS4594, and used to amplify ten strains having SPC-P1 in the genome. The PCR products were sequenced to investigate the integration sites of SPC-P1. RESULTS: SPC-P1 was widely distributed in S.paratyphi C genome. In the study, 14 strains had all 6 fragments and 2 strains had 3-5 fragments. All the amplified fragments showed expected sizes. In contrast, in the genomes of S. typhi, S. paratyphi A and S. paratyphi B, no or only 1-2 fragments could be amplified, and the sizes were smaller than expected. The results from Mauve showed that only in the genome of S.choleraesuis, which was a close relative of S. paratyphi C, there existed an almost complete genome of SPC-P1. The insertion site of SPC-P1 in all the ten S. paratyphi C strains tested was between pgtE and yfdC genes. CONCLUSION: SPC-P1 is a unique virulence factor of S. paratyphi C. It may play roles in the host range and pathogenicity of S.paratyphi C. PMID- 26679651 TI - [Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabetes and coronary artery disease]. AB - OBJECTIVE: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD). METHODS: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. RESULTS: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687+/-3 052) ng/g, while the urinary 11dhTxB2 was (1 954+/-859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05). CONCLUSION: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD. PMID- 26679652 TI - [Sucrose gel for treatment of bacterial vaginosis: a randomized, double-blind, multi-center, parallel-group, phase III clinical trial]. AB - OBJECTIVE: To evaluate the cure effectiveness and safety of sucrose gel in the treatment of bacterial vaginosis through a multi-center, randomized, double blind, parallel controlled clinical study. METHODS: A clinical research method of multi-center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 533 patients with bacterial vaginosis were randomly divided into two groups, which included 214 cases in the control group (5.0 g metronidazole gel) and 319 cases in the trial group (5.0 g sucrose gel ). The patients were treated with different medication according to the group where they were. All the cases in these two groups were treated with drugs vaginally twice in a day, morning and evening separately, for 5 days. The curative effect and safety evaluation were assessed from 7 to 10 days and 21 to 30 days after treatment respectively. RESULTS: The efficacy of the comprehensive clinical treatment showed that the cure rate of metronidazole gel group and sucrose gel group were 70.53% and 80.83% respectively 7 to 10 days after treatment. The recovery rate of Nugent score for vaginal smear were 71.50% and 81.15% respectively. The differences in the efficacy between these two groups were significant statistically (P<0.05). However, the cure rates of metronidazole gel group and sucrose gel group were 63.29% and 61.98% respectively 21 to 30 days after treatment. No statistically significant difference (P>0.05) could be found in the cure rates of the two groups. CONCLUSION: The clinical comprehensive efficacy and recovery of vaginal bacteria of sucrose gel group in the treatment of bacterial vaginosis were obviously superior to those of metronidazole gel 7 to 10 days after treatment. The susucrose gel could improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina according to the Nugent score. The curative efficacy of sucrose gel was equal to that of metronidazole gel 21 to 30 days after treatment. In the future, sucrose gel treatment can be a new strategy for the treatment of bacterial vaginosis. Various advantages can be taken to improve the cure rate of bacterial vaginosis and reduce the shortcomings produced by this disease. PMID- 26679653 TI - [Confocal laser scanning electron microscopy for assessment of vaginal Lactobacillus crispatus biofilm]. AB - OBJECTIVE: To investigate the female vaginal Lactobacillus crispatus biofilm by using confocal laser scanning microscopy (CLSM),thus revealing the formation of biofilm. METHODS: The cover slide biofilm culture approach in vitro was employed for induction of the vaginal Lactobacillus crispatus biofilm formation. Following the culture for 2, 4, 8, 12, 16, 20, 24, 48, 72, 96 and 120 hours, the cover slide was removed for subsequent staining with the fluoresce in isothiocyanate conjugated concanavalin A(FITC-ConA) and propidium (PI).This was followed by determination of the formation and characteristics of the vaginal Lactobacillus crispatus biofilm by using CLSM. RESULTS: The CLSM images of biofilm formation at different time points were captured, suggesting that the vaginal Lactobacillus crispatus adhesion occurred at h 4, which was in reversible attachment, then more and more Lactobacillus crispatus aggregated at h 8 to h 20, which was in irreversible attachment.Lactobacillus crispatus clustered at h 20, with early development of biofilm architecture.Then the biofilm with extracellular matrix around the bacteria was set up at h 24,with gradual matureation at h 24 to h 48.The biofilm dispersed at h 72. The biofilm density of cultivating for 20 hours was 42.7 * 10-3 +/- 6.8 * 10-3 ,and for 24 hours increased to 102.5 * 10-3 +/- 23.1 * 10-3, suggesting a significant difference, P<0.05. This meant that mature biofilm was formed at h 24. CONCLUSION: The vaginal Lactobacillus crispatus is able to form typical biofilm with distinct developmental phases and architecture characteristics.Mature biofilm is formed at h 24 to h 48, then the biofilm begins to disperse. PMID- 26679654 TI - [Sporadic cutaneous infections due to nontuberculous mycobacteria: a retrospective study of 37 cases]. AB - OBJECTIVE: To study the clinical and pathological characteristics of sporadic cutaneous infections due to nontuberculous mycobacteria (NTM), and investigate the diagnostic criteria and therapeutic principal. METHODS: Totally 37 cases of sporadic cutaneous infections due to NTM were confirmed in the Department of Dermatology, Peking University People's Hospital from January 2000 to March 2014. The microbiologic and clinical data were reviewed, and their skin biopsy specimens were reassessed. RESULTS: Of all the 37 patients, 30 cases were Mycobacterium marinum infection, 6 were Mycobacterium abscessus infection, and one was Mycobacterium chelonea and Mycobacterium fortuitum infection. Identification of mycobacterial species by analysis of hsp65 gene in tissue DNA was more sensitive than traditional bacterial culture. The most common risk factors were traumatic injuries (21 of 37) and aquarium or fish-related job (21 of 37). One case of Mycobacterium abscessus infection occurred after autologous fat filling. Nodule and plaque were most common lesions in Mycobacterium marinum infection. Twenty-four of the 30 cases of Mycobacterium marinum infection presented with multiple lesions or sporotrichoid spread lesions. Ulceration, papules, abscess, and purulent discharge were observed in cases of Mycobacterium abscessus infection. Infective granuloma was most common histopathological appearance. For the treatment of Mycobacterium marinum infection, rifampin, ethambutol, and clarithromycin were commonly used (combination of two antibiotics, or three antibiotics), with the cure rate 90.00%. Four of the six Mycobacterium abscessus infections cases were cured, and one patient died. CONCLUSION: The most common species of sporadic cutaneous infections due to NTM is Mycobacterium marinum. Traumatic injuries, aquarium or fish-related job, and cosmetic surgeries are common risk factors. Mycobacterium marinum infection often presents with nodules, plaques, and sometimes sporotrichoid spread lesions. Lesions of Mycobacterium abscessus infection may vary. Pathological changes were not species specific, final diagnosis must be made depending on the identification of the microorganism. For the treatment of Mycobacterium marinum infection, excellent outcomes can be achieved by the combination of rifampin and ethambutol, and the combination of clarithromycin and rifampin or ethambutoland. Treatment regimens of Mycobacterium abscessus infection should be decided according to the results of antibiotic susceptibility testing. PMID- 26679655 TI - [Application of endoscopic submucosal dissection in treatment of early gastric cancer]. AB - OBJECTIVE: To evaluate the clinical outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in a single center in China. METHODS: We performed a retrospective analysis of the patients with single EGC lesion who received ESD in Peking University Cancer Hospital from January 2011 to December 2013.Their clinicopathologic data, resectability, curability, complications and follow-up data were assessed. RESULTS: A total of 116 patients were enrolled in the study. The patients included 88 men and 28 women, with a median age of 63 years (range: 25-80 years).The post-operative histology of the lesions included 28 (24.1%) high grade intraepithelial neoplasia, 35 (30.2%) well differentiated adenocarcinoma, 35 (30.2%) moderated differentiated adenocarcinoma and 18 (15.5%) poorly differentiated adenocarcinoma. Of all the lesions, 75.0% (87/116) were confined into mucosa, 15.5% (18/116) invaded SM1 (<500 MUm from the muscularis mucosae) and 9.5% (11/116) invaded SM2 (>= 500 MUm from the muscularis mucosae). The mean tumor size was (1.49 +/- 0.96) cm, and the rate of ulceration was 14.7% (17/116). The en bloc resection rates were 96.7% (111/116), complete resection rates were 93.1% (108/116) and curative resection rates were 77.6% (90/116). According to the curability, 62 (53.4%) cases were classified into the standard curative resection (sCR) group, 28 (24.2%) into the expanded curative resection (eCR) group and 26 (22.4%) into the non-curative resection (nCR) group. The mean tumor size of the sCR group was smaller than that of the eCR and nCR group (t= 4.121, P<0.001 and t=-3.420, P=0.001). In the nCR group, the portion of type 0 III lesion and ulceration were significantly higher (chi2 = 10.287, P=0.006 and chi2 = 17.737, P<0.001). In multivariate analysis, EGC with ulceration and submucosal invasion were the risk factors for non-curative resection (OR=6.634, P=0.006 and OR=12.735, P<0.001). The ESD-related complications included 4 (3.4%) post-operative bleeding, 3 (2.6%) intra-operative perforation, 2 (1.7%) cardiac stenosis and 1 (0.9%) heart failure. In the study, 106 of the 116 patients received periodic follow-up, during a median follow-up of 22 months (12-47 months). Local tumor recurrence developed in 1 patient of the eCR group 8 months post the ESD. CONCLUSION: ESD is a safe and feasible option for EGC in China, ulceration and submucosal invasion are associated with non-curative resection, and post-operative bleeding and intra-operative perforation should be concerned as the main complications. PMID- 26679656 TI - [Errors in six degree-of-freedom pose estimation of spine tumors assessed by image guided radiotherapy]. AB - OBJECTIVE: To evaluate the six-degree setup errors of tumors of cervical vertebra, thoracic vertebra and lumbar vertebra by image guided radiotherapy. METHODS: From May 2013 to June 2014, 30 patients with spinal malignant tumors(10 patients of cervical vertebra, thoracic vertebra and lumbar vertebra respectively) were treated with Elekata Synergy accelerator (Elekta company,Sweden). Six-degree set up errors were corrected using HexaPODTMevoRT bed under image of on board cone beam computed tomography (CBCT) guided. All the patients received kilovoltage CBCT before receiving radiotherapy and after correction. The acquired images were co-registered with planning CT with bone window. The data of 838 CT images were analyzed and the errors of translational directions X(lateral), Y(lngitudinal),Z(vertical)and rotational directions RX(pitch), RY(roll), RZ(yaw) were recorded. The data were compared by t-test using SPSS 13.0. RESULTS: The absolute translational setup errors in X, Y and Z axes of cervical vertebra before correction were (1.71 +/- 0.10) mm, (1.81 +/- 0.11) mm and (1.94 +/- 0.09) mm respectively: (3.17 +/- 0.19) mm, (4.26 +/- 0.28) mm and (2.18 +/- 0.12) mm for thoracic vertebra, and (2.69 +/- 0.24) mm, (3.33 +/ 0.26) mm and (2.86 +/- 0.21) mm for lumbar vertebra. The residual setup errors in X, Y and Z axes of cervical vertebra were (0.5 +/- 2.4) mm,(0.01 +/- 2.4) mm and (2.4 +/- 1.4) mm, respectively after correction;(1.17 +/- 0.11) mm,(0.26 +/- 0.30) mm and (0.08 +/- 0.12) mm for thoracic vertebra and (1.09 +/- 0.24) mm,(2.03 +/- 1.26) mm and (0.06 +/- 0.51) mm for lumbar vertebra. The t-test of paired data of set up errors before and after CBCT showed significant difference in three translational directions of cervical vertebra and thoracic vertebra, only Z(t=-3.518,P<0.001) for lumbar vertebra. The absolute rotational setup errors in RX,RY and RZ axes of cervical vertebra before correction were 0.67 degrees +/- 0.04 degrees ,1.06 degrees +/- 0.06 degrees and 0.78 degrees +/- 0.05 degrees respectively. 0.62 degrees +/- 0.05 degrees , 0.75 degrees +/- 0.06 degrees , and 0.84 degrees +/- 0.06 degrees for thoracic vertebra, 0.59 degrees +/- 0.06 degrees , 0.80 degrees +/- 0.07 degrees , and 0.73 degrees +/ 0.06 degrees for lumbar vertebra. The rotational directions RX, RY and RZ axes of cervical vertebra were 0.27 degrees +/- 0.14 degrees , 1.20 degrees +/- 0.04 degrees and 0.28 degrees +/- 0.05 degrees respectively; 0.02 degrees +/- 0.20 degrees , 0.05 degrees +/-0.26 degrees and 0.64 degrees +/- 0.16 degrees for thoracic vertebra and 0.09 degrees +/- 0.26 degrees , 0.50 degrees +/-0.05 degrees ,and 0.03 degrees +/-0.16 degrees for lumbar vertebra. The t-test of paired data of set up errors before and after CBCT showed significant difference in three rotational directions of cervical vertebra and lumbar vertebra, only RY(t=7.106, P<0.001)for thoracic vertebra. All the patients acquired pain relief and there was no radiation-induced toxicity detected clinically during a median follow-up of 6 months. CONCLUSION: Six-degree set up errors of spine tumors were corrected effectively with HexaPODTMevoRT bed under CBCT image guided and its feasibility in day-to-day clinical practice has been demonstrated. PMID- 26679657 TI - [Comparison of the clinical efficacy of endovascular reconstruction versus bypass surgery for transatlantic inter-society consensus II C/D femoropopliteal artery lesion resulted from arteriosclerosis obliterans]. AB - OBJECTIVE: To study the clinical effects of endovascular reconstruction versus bypass surgery for TASC II(trans-atlantic inter-society consensus II) C/D femoropopliteal artery lesion resulted from arteriosclerosis obliterans. METHODS: One hundred and three patients(119 limbs)accepted bypass surgery or endovascular therapy for TASCII C/D femoropopliteal artery lesion between January 2002 and December 2012 at our institution were retrospectively assessed.All the patients were diagnosed with arteriosclerosis obliterins, and all their Rutherford classifications were from 2 to 5 degrees.Among them there were 71 limbs treated by endovascular reconstruction and the other 48 limbs were treated with bypass surgery.We evaluated the short term clinical effect according to the condition when patients left the hospital, and evaluated the long term clinical effect according to the results of the patients' latest follow-up in 2014. Their clinical data before treatment, complication rates, death rates, hospital stays, short term and long term effects, reoperation rates, 1 to 10 years primary and secondary accumulative patency rates and limb salvage rates were compared. RESULTS: There was no significant difference between the bypass group and the endovascular group on the mean age and ankle brachial index before treatment [(67.1 +/- 7.1) years(51 to 80 years) vs. (68.0 +/- 9.4) years (49 to 91 years), P=0.561;(0.41 +/- 0.23) vs. (0.40 +/- 0.26), P=0.928]. There were more TASCII D patients in the bypass group than those in the endovascular group (P<0.001), and the rutherford classification was higher in the endovascular group than that in the bypass group. The difference in the mean follow-up between the bypass group and the endovascular group was not significant [(41.7 +/- 23.6) months vs. (59.5 +/- 41.6) months, P=0.065]. Five peri-operative complication cases occurred in the bypass group, including 2 cases of acute thrombosis,1 case of infection and 2 cases of heart failure, and only 1 complication case occurred in the endovascular group that was heart failure.The complication rate was higher in the bypass group than that in the endovascular group [10.4% vs. 1.4%, P=0.039]. And there was no death in both the groups.Compared with the endovascular group, the bypass group had a longer hospital stays [(13.2 +/- 4.7) d vs.(6.5 +/- 3.1) d, P<0.001], a higher reoperation rate (58.3% vs.31.0%,P=0.003), a better short term, obvious, and effective rate (25.0% vs. 9.9%, P=0.027), a worse long term deterioration rate (37.5% vs. 18.3%, P=0.019) and higher 1 to 10 years primary and secondary accumulative patency rates(P=0.001, P=0.001).There was no significant difference between the two groups on the increase of ankle brachial index [(0.34 +/- .28) vs. (0.31 +/- 0.23), P=0.371], and short term and long term total effective rates (89.6% vs.84.5%, P=0.426; 45.8% vs. 56.3%, P=0.260), and limb salvage rate (83.3% vs.94.4%, P=0.051). CONCLUSION: Endovascular therapy is a safe, effective and minimally invasive therapy for TASCII C/D femoropopliteal artery lesion resulted from arteriosclerosis obliterans. PMID- 26679658 TI - [Clinical analysis of 31 ankylosing spondylitis patients with malignancies]. AB - OBJECTIVE: To investigate the clinical features of patients with ankylosing spondylitis (AS) and malignancies. METHODS: In the study, 31 AS patients with malignancies in Peking University First Hospital from January 2006 to July 2014 were enrolled, and their clinical features were compared with AS patients without malignancies at the same time in the hospital. Then their general characteristics, clinical and imaging findings of AS, characteristics of malignancies and prognosis were retrospectively analyzed. RESULTS: The 31 cases of AS with malignacies accounted for 11.8% of all AS patients admitted to the hospital in the same period. They comprised of 27 males (87%) and 4 females (13%). Their mean ages at diagnosis of AS were 43+/-17 years (range: 16-76 years), and their mean ages at diagnosis of malignancy were 60+/-12 years (range: 31-87 years) respectively. Malignancy was diagnosed after the establishment of AS in 27 of our patients. Furthermore, imaging changes typical of AS were found in all the 31 patients at the diagnosis of AS, but the majority of them had never received any proper treatment for AS. The malignancies of 31 AS patients included bladder cancer (7 cases), hematological malignancy (6 cases), lung cancer (5 cases), renal cancer (5 cases), prostate cancer (2 cases), carcinoma of renal pelvis (2 cases), breast cancer (2 cases), gastric carcinoma (2 cases), rectal cancer (2 cases), neuroendocrine carcinoma (2 cases), colon carcinoma (1 case), and esophagus cancer (1 case). CONCLUSION: There is risk of malignancy in AS. Malignancy is not rare in patients with AS. Bladder cancer is the most common one followed by hematological malignancy. In consequence, close attention should be paied to the conditon of AS with malignancy in clinical practice. PMID- 26679659 TI - [Relative factors of type II endoleak after endovascular aneurysm repair]. AB - OBJECTIVE: To study the relative factors of type II endoleak after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms. METHODS: Twenty-eight cases of abdominal aortic aneurysms treated by EVAR were retrospectively analyzed. The characteristics of the inferior mesentery arteries (IMA), the arc Riolan and the lumbar arteries of the cases with or without type II endoleak were analyzed. RESULTS: Type II endoleak was found in 8 (28.6%) cases, of which, 2 were type IIa and 6 were type IIb. The diameter of the IMA originating part of the cases with type II endoleak [(4.03 +/- 1.00) mm] was significantly bigger than that without endoleak [(2.89 +/- 0.50) mm, P=0.007]. The number of the lumbar arteries originating from the aneurysm sac in cases with type II endoleak (3.4 +/- 0.8) was significantly more than that without endoleak (1.9 +/- 1.5, P=0.017). However, type II endoleak was irrelevant to the diameter of originating part of the lumbar arteries and the form of the arc Riolan. After the average 14.5 months follow-up, the aneurysm sac was found with shrinkage in 1 case, no change in 2 cases, and augment in 5 cases. Secondary transarterial embolization was performed for only 1 case. CONCLUSION: Type II endoleak was much easily found in cases with bigger diameter of originating part of the IMA, or in cases with more lumbar arteries originating from the aneurysm sac. PMID- 26679660 TI - [Short-term effect of CaCl2on human adipose-derived mesenchymal stem cells proliferation and osteogenic differentiation]. AB - OBJECTIVE: To examine the effect of CaCl2, a sodium alginate crosslinker, to stimulate cells for a short time period on human adipose-derived mesenchymal stem cells (hASCs) proliferation and osteogenic differentiation ability, and to determine the appropriate concentration of CaCl2for post three-dimensional biological experiments. METHODS: hASCs stimulated with or without CaCl2at various concentrations were seeded and cultured in control medium and osteogenic medium, respectively. The cell counting kit-8 (CCK8) was used to estimate the cell proliferation level of each group. After 7 days of osteogenic induction, alkaline phosphatase (ALP) staining and activity assays were performed using an ALP kit. After 14 days of osteogenic induction, alizarin red staining and quantitative detection were used to determine the calcium mineral density. The results were analyzed using analysis of variance (ANOVA) and Student-Newman-Keuls (SNK) tests for pairwise comparisons implemented in the SPSS 17.0 software. RESULTS: The CCK 8 assays showed that the differences between the control groups and experimental groups were not statistically significant, so different concentrations of CaCl2had no significant effect on hASCs proliferation. The ALP staining and activity assays showed that ALP activity first increased and then decreased as the CaCl2concentration increased. Furthermore, the differences between all the groups were statistically significant (P<0.05), except the difference between the 50 mmol/L CaCl2group and the 100 mmol/L CaCl2group, and between the osteogenetic medium(OM) group and the 200 mmol/L CaCl2group. Alizarin red staining and quantitative detection showed that the differences between all pairwise combinations of the groups were statistically significant (P<0.05). As the CaCl2 concentration increased, the calcium deposition increased, initially in the form of a scattered sheet and eventually a laminated sheet. CONCLUSION: Stimulation by a high concentration of CaCl2over a short time period can enhance hASCs osteogenic differentiation ability, but has no effect on hASCs proliferation. PMID- 26679661 TI - [Effect of peroxisome proliferator-activated receptor-gamma on endothelial cells oxidative stress induced by Porphyromonas gingivalis]. AB - OBJECTIVE: To detect the degree of oxidative stress in the process when Porphyromonas gingivalis (P. gingivalis) stimulates human vascular endothelium, And to investigate the effect of peroxisome proliferator-activated receptor(PPAR)gamma on oxidative stress during this process. METHODS: Human vascular endothelial cells (HVECs) line EA.hy926 (American Type Culture Collection ,United States) was cultured in high glucose Dulbecco's modified eagle medium (DMEM). Four groups were designed: control group, P. gingivalis infected group, PPARgamma activated group and PPARgamma blocked group. In control group HVECs were cultured with only DMEM. In P. gingivalis infected group, HVECs were time-dependently stimulated by P. gingivalis W83 from 0 to 12 h. In PPARgamma activated group or PPARgamma blocked group, PPARgamma was pre-activated or blocked by a representative PPARgamma agonist(15d-PGJ2 10 MUmol/L) or antagonist (GW966210 MUmol/L) 30 minutes before the cells were stimulated by P. gingivalis. At 0, 0.5, 1, 1.5, 2, 4, 8, and 12 h, the culture medium was collected individually and centrifuged, and the supernatant was stored for assay. Glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) were analysed by enzyme linked immunosorbent assay. Cellular reactive oxygen species (ROS) were detected through 2',7'-dichlorofluorescin diacetate (DCFA-DA) fluorescent probe at various time points of the different groups. RESULTS: In P. gingivalis infected group, the levels of GSH-PX [(5.56+/-0.97) MUmol/L] and MDA [(0.84+/-0.18) nmol/L] were significantly higher than those in control group [GSH-PX(4.71+/-0.64) MUmol/L, MDA (0.59+/-0.18) nmol/L)]. The levels of GSH-PX and MDA in PPARgamma activated group [GSH-PX (5.38+/-0.84) MUmol/L, MDA (0.84+/-0.22) nmol/L] and in PPARgamma blocked group [GSH-PX (5.37+/-0.76) MUmol/L, MDA (0.85+/-0.14) nmol/L] were significantly higher than those in control group (P<0.05). In the PPARgamma activated group, the levels of GSH-PX at 0.5 and 8 h were significantly higher than those from 1.5 h to 4 h (P<0.05), while no difference was observed on the MDA levels at different time points. There was no significant difference at various time points for the levels of GSH-PX and MDA in PPARgamma blocked group. The level of cellular ROS detected by DCFH-DA in P. gingivalis infected group was significantly higher than that in control group (10 108.65 +/- 1 805.18 vs. 6 049.06 +/- 1 199.19,P<0.05). No difference was observed between PPARgamma activated group (7 120.94+/-1 447.30) or PPARgamma blocked group (6 727.35+/-1 483.68) and control group. CONCLUSION: Oxidative stress happens when P. gingivalis stimulates human vascular endothelium. PPARgamma may involve in modulating oxidative stress during this process. PMID- 26679662 TI - [Analysis of volatile sulfur compounds production of oral cavity in preschool children and influencing factors]. AB - OBJECTIVE: To investigate the prevalence of volatile sulfur compounds(VSC) in oral cavity of preschool children, and to analyze related factors, thus to provide scientific basis for the prediction and treatment of halitosis. METHODS: The VSC content (hydrogen sulfide, methyl mercaptan, dimethyl sulfide) of 170 preschool children (4 to 6 years old) was detected by a portable gas chromatograph OralChromaTM. The status of the oral health was evaluated. The living habits and other aspects were obtained through questionnaires from the children's parents. A soft package for social statistics version 13.0 (SPSS 13.0) was used in which univariate analysis and multivariate analysis were utilized to analyze the related factors of halitosis in children. RESULTS: In the study, 34.4% of the total subjects had excessive VSC. Hydrogen sulfide (H2S) [(1.59 +/- 2.41) ng/10 mL] and total VSC concentration [(2.14 +/- 4.42) ng/10 mL] in the girls were significantly higher (P<0.05) than those in the boys. The tongue coating score had a significant positive correlation with H2S [tongue coating area (1.68 +/- 2.48) ng/10 mL,tongue coating thickness (2.18 +/- 2.69) ng/10 mL] and total VSC concentration [tongue coating area, (2.26 +/- 4.31) ng/10 mL,tongue coating thickness (2.41 +/- 3.02) ng/10 mL , P<0.01]. The site number of DI-S >= 2 had a significant positive correlation with methyl mercaptan (CH3SH) and dimethyl sulfide [(CH3)2S] concentration (P<0.01). The concentration of H2S [(1.19 +/- 1.62) ng/10 mL] in children, whose mother had a higher degree of education, was statistically lower (P<0.01). The children who took dessert or sweat drinks more frequently had lower H2S [(1.04 +/- 1.55) ng/10 mL, P<0.05] concentration, while CH3SH and (CH32)S concentration [(0.29 +/- 1.92) ng/10 mL, (0.37 +/- 2.06) ng/10 mL, P<0.05) were higher in the children with mouth-breath habit. CONCLUSION: A high prevalence of halitosis was noted in preschool children. Gender, tongue coating index, debris index-simplified, status of the mother's education, frequency of eating dessert or sweat drinks and dry mouth breath were related with halitosis of preschool children. The different related factors resulted in changes of each VSC concentration. PMID- 26679663 TI - [Bond strengths of absorbable polylactic acid root canal post with three different adhesives]. AB - OBJECTIVE: To find absorbable adhesives with suitable bonding properties for the absorbable polylactic acid root canal post. To test and compare the bond strengths of absorbable polylactic acid root canal post with three different adhesives. METHODS: The absorbable polylactic acid root canal posts were used to restore the extracted teeth, using 3 different adhesives: cyanoacrylates, fibrin sealant and glass ionomer cement. The teeth were prepared into slices for micro push-out test. The bond strength was statistically analyzed using ANOVA. The specimens were examined using microscope and the failure mode was divided into four categories: cohesive failure between absorbable polylactic acid root canal posts and adhesives, cohesive failure between dentin and adhesives, failure within the adhesives and failure within the absorbable polylactic acid root canal posts. RESULTS: The bond strength of cyanoacrylates [(16.83 +/- 6.97) MPa] and glass ionomer cement [(12.10 +/- 5.09) MPa] were significantly higher than fibrin sealant [(1.17 +/- 0.50) MPa], P<0.001. There was no significant difference between cyanoacrylates and glass ionomer cement (P=0.156). In the group of cyanoacrylates, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 25.0%, the cohesive failure between the dentin and the adhesives was 16.7%, the failure within the adhesives was 33.3%, and the failure within the absorbable polylactic acid root canal posts was 25.0%. In the group of fibrin sealant, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 66.7%, the cohesive failure between the dentin and the adhesives was 22.2%, the failure within the adhesives was 11.1%. In the group of glass ionomer cement, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 87.5%, the failure within the adhesives was 12.5%. The major failure mode in fibrin sealant and glass ionomer cement was the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives. No major failure modes were found in the group of cyanoacrylates. CONCLUSION: The bond strength of fibrin sealant is low, which cannot meet the requirement of clinical use. The bond strengths of cyanoacrylates and glass ionomer cement are suitable for clinical use. The cyanoacrylates are a kind of absorbable adhesive which has suitable bonding properties for the absorbable polylactic acid root canal post. PMID- 26679664 TI - [Measurement and analysis of the nasopalatine canal and its relative position by cone-beam computed tomography]. AB - OBJECTIVE: To evaluate dimensions of the nasopalatine canal and the relationship between the canal and the central incisors, and the canal and the crest, by using cone-beam computed tomography (CBCT). METHODS: This study included 129 CBCTs, and the sagittal slices were used to measure the lower diameter (Sda), median diameter (Sdb), and higher diameter (Sdc), for calculating the average sagittal diameter (Sd); the coronal slices through canals were used to measure the lower diameter (Hda), median diameter (Hdb), and higher diameter (Hdc) for calculating the average horizontal diameter (Hd), length (H); the sagittal slices were used to measure the buccal bone thickness off the canal (Bt), and the distance to the crest off the lowest point (At), the horizontal slices were used to measure the distance between the canal and the central incisors (Id). These subjects were divided into two groups by gender; and divided into three groups by ages: (1) <= 30 years old, (2) 31-50 years old, and (3) >= 51 years old. SPSS 17.0 statistical software was used for statistical analysis. RESULTS: The overall Sd was (3.41 +/ 0.87) mm, the Hd was (5.16+/-0.93) mm, and the difference was statistically significant. The H was (14.29 +/- 3.27) mm, the Bt was (7.49 +/- 1.05) mm, the At was (8.25 +/- 1.71) mm, and the Id was (2.71+/-0.89) mm. Of the male and female, the Sd were (3.64 +/- 0.90) mm and (3.28 +/- 0.82) mm, P=0.017; the Hd were (4.98 +/- 0.89) mm and (5.27 +/- 0.94) mm, P=0.081; the H were (15.47 +/- .75) mm and (13.59 +/- 3.32) mm, P=0.001; the Bt were (7.90 +/- 0.96) mm and (7.25 +/- 1.03) mm, P=0.001; the At were (7.41 +/- 1.86) mm and (8.44 +/- 1.90) mm, P=0.001; the Id were (2.71 +/- 0.87) mm and (2.72 +/- 0.91) mm, P=0.983. Among the groups, no statistically significant differences were detected of the Sd (P=0.325), of the Hd (P=0.636), of the H (P=0.292), and of the Bt (P=0.116); statistically significant differences were detected of the At (P=0.010), and of the Id (P<0.001). CONCLUSION: The nasopalatine canal anatomy is highly variable. Gender is related to the nasopalatine canal length, Bt width, and At distance. While age was related to At, and Id, but no effect on nasopalatine dimensions. The CBCT is a useful device for studying the nasopalatine canal in three dimensions, prior to dental implant placement. PMID- 26679665 TI - [Resting pressure of the tongue body on the tongue anchorage pad]. AB - OBJECTIVE: To measure the resting pressure of the tongue body on the sagittal and vertical dimensions of the tongue anchorage pad (TAP), and to investigate the proper position of TAP as an anchorage. METHODS: Nineteen volunteers with individual normal occlusion (4 males and 15 females, age 23-33 years) were recruited in the study. Individualized TAP was designed and made for each subject. On the sagittal dimension, the pressure along the midline at the level of the distal of the second premolar (PM2), the first molar (M1) and the second molar (M2) were measured. On the vertical dimension, pressures on TAPs with height of -3 mm, 0 mm, and 3 mm were measured, with 0 mm standing for the reference point recorded by the tongue position record. The tongue resting pressure of the volunteers in the upright position was measured by miniature sensors (FSS1500NS, Honeywell, USA) embedded in TAP. Nonparametric analysis was applied with the significant level of 0.05. RESULTS: On the vertical dimension, the pressure obtained at the height of -3 mm, 0 mm, and 3 mm were 105.83 Pa, 167.75 Pa, and 254.25 Pa, respectively (P<0.001). On the sagittal dimension, the pressure detected at the level of PM2, M1, and M2 were 177.64 Pa, 126.72 Pa, and 109.37 Pa, respectively (P<0.001). CONCLUSION: Tongue pressure rises significantly with the increase of TAP height. On the sagittal dimension, pressure decreases along the palatal midline in an anteroposterior direction. But in the clinical practice, we should also put comfort into consideration. PMID- 26679666 TI - [Comparative research for micro-push-out bond strengths of glass fiber posts treated by poly-dopamine or silane coupling agent]. AB - OBJECTIVE: To evaluate the micro-push-out bond strengths of prefabricated glass fiber posts with poly-dopamine functionalized to root dentin using resin cements, contrasted with silane treatment. METHODS: In the study, 30 glass fiber posts were randomly divided into 3 groups (10 posts in each group) for different surface treatments. Group 1, treated with poly-dopa; Group 2, treated with silane coupling agent for 60s; Group 3, no surface treatment (Control group). The 30 extracted human, single-rooted teeth were endodontically treated and a 9 mm post space was prepared in each tooth with post drills provided by the manufacturer. Following post cementation, the specimens were stored in distilled water at 37 degrees C for 7 days. The micro-push-out bond strengths were tested using a universal testing machine (0.5 mm/min), and the failure modes were examined with a stereomicroscope. The data of the three groups were statistically analyzed using the one-way ANOVA test(alpha= 0.05). RESULTS: The bond strengths were (7.909 +/- 1.987) MPa for Group 1, (5.906 +/- 0.620) MPa for Group 2, and 4.678 +/- 0.910 MPa for Group 3. The bond strength of poly-dopamine group was significantly higher than that of the silane group (P<0.05). CONCLUSION: Contrasted with silane treatment, surface poly-dopamine functionalization was confirmed to be a more reliable method for improving the bond strength of resin luting agents to fiber posts. PMID- 26679667 TI - [Application of flexible laryngeal mask airway in oral & maxillofacial day surgery]. AB - OBJECTIVE: To access the feasibility and safety of application of flexible laryngeal mask airway (FLMA) in oral & maxillofacial day surgery. METHODS: Retrospective study was conducted of 40 oral & maxillofacial day surgery patients (3 to 61 years of age) using FLMA under general anaesthesia in Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology. All the patients were with American Society of Anesthesiologists(ASA) physical status I-II,including 19 males and 21 females. The patients'vital signs were recorded at five different time points: baseline before anesthesia (T0), time right after the FLMA insertion (T1), time at incision (T2), 15 min after incision (T3) and time at the end of the operation (T4). The first attempted FLMA insertion successful rate and the number of timed of changing to endotracheal intubation were recorded. During operation, frequencies of movement, hypoxia and obstruction of airway were noted and the operation time, anesthesia time, time from the end of the operation to extubation, movement and coughing following extubation and sore throat within 24 h were taken down. Operation-related complications of bleeding, hematoma and injury of local nerves were recorded within 24 h as well. RESULTS: The operations of all the 40 patients were successfully done under general anaesthesia. The 36(90%, 36/40)patients using FLMA successfully were under steady process, including 16 males and 20 females. The first attempted successful rate of FLMA insertion was 80% (32/40), and the second 50% (4/8). Three out of the 4 failed FLMA patients were changed to endotracheal intubation after the second attempt failed. The other patient was changed to endotracheal intubation before operation because of leak. The average operation time was (46.58 +/- 22.57) min, the anesthesia time was (77.97 +/- 26.82) min and the time from the end of operation to extubation was (8.31 +/- 3.33) min. All the patients were recorded without obvious body movement during the operation procedure. There were 4 patients (11.11%, 4/36) with slight body movement during extubation. The incidence of sore throat was 13.89% (5/36) within 24 h postoperatively. There were no complications of bleeding, hematoma and injury of local nerves. The vital signs of baseline T0 were significantly different from those at other time points T1, T2, T3, and T4 (P<0.01). As to the hearts rate after anesthesia, the values at T1, T2, T3 and T4 for two-two comparison, there was no statistical difference (P>0.05). As to the values of systolic blood pressure and diastolic blood pressure after anesthesia at T1 and T4, T2 and T3, for two-two comparison, there was no statistical difference (P>0.05). As to the respiratory rate from the start of the surgery, the values at T2, T3 and T4 showed no statistical difference (P>0.05). CONCLUSION: Flexible laryngeal mask airway is a supraglottic airway management method. It is suitable and safe for securing the airway in oral & maxillofacial day surgery. The advantages of fewer haemodynamic changes and postoperative complications are confirmed. PMID- 26679668 TI - [Finite element analysis of the maxillary central incisor with crown lengthening surgery and post-core restoration in management of crown-root fracture]. AB - OBJECTIVE: To construct the finite element models of maxillary central incisor and the simulations with crown lengthening surgery and post-core restoration in management of different crown-root fracture types, to investigate the stress intensity and distributions of these models mentioned above, and to analyze the indications of crown lengthening from the point of view of mechanics. METHODS: An extracted maxillary central incisor and alveolar bone plaster model were scanned by Micro-CT and dental impression scanner (3shape D700) respectively. Then the 3D finite element models of the maxillary central incisor and 9 simulations with crown lengthening surgery and post-core restoration were constructed by Mimics 10.0, Geomagic studio 9.0 and ANSYS 14.0 software. The oblique static force (100 N) was applied to the palatal surface (the junctional area of the incisal 1/3 and middle 1/3), at 45 degrees to the longitudinal axis, then the von Mises stress of dentin, periodontal ligament, alveolar bone, post and core, as well as the periodontal ligament area, were calculated. RESULTS: A total of 10 high-precision three-dimensional finite element models of maxillary central incisor were established. The von Mises stress of models: post>dentin>alveolar bone>core>periodontal ligament, and the von Mises stress increased linearly with the augmentation of fracture degree (besides the core). The periodontal ligament area of the crown lengthening was reduced by 12% to 33%. The von Mises stress of periodontal ligament of the B2L2c, B2L3c, B3L1c, B3L2c, B3L3c models exceeded their threshold limit value, respectively. CONCLUSION: The maxillary central incisors with the labial fracture greater than three-quarter crown length and the palatal fracture deeper than 1 mm below the alveolar crest are not the ideal indications of the crown lengthening surgery. PMID- 26679669 TI - [Autoimmune lymphoproliferative syndrome: a case report and literature review]. AB - We described 1 case of autoimmune lymphoproliferative syndrome (ALPS), first diagnosed in our hospital, and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection, parvovirus B19 infection and chronic diarrhea disease. Besides, his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha/beta double negative T cells (DNTs) (27.18% of lymphocytes, 35.16% of CD3+ T lymphocytes) in peripheral blood, and autoantibodies including antinuclear antibody, double stranded DNA and rheumatic factor were positive. Hyper gamma globulinemia and positive direct Coombs tests were seen in the patient. His parents were both healthy and denied autoimmune diseases. We identified a heterozygous point mutation in exon 3 of the FAS gene carrying c.309 A>C, resulting in a single base pair substitution in exon 3 of FAS gene which changed the codon of Arg103 to Ser103. Unfortunately, we were unable to obtain the gene results of the child's parents. The patient was treated with glucocorticoids in our hospital and with mycophenolatemofetil in other hospital. And we were informed that his anemia condition relieved through the telephone follow-up, but he still suffered recurrent infections, hepatomegaly and splenomegaly still existed. As we all know ALPS is characterized by defective lymphocyte apoptosis, and thus cause lymphoproliferative disease and autoimmune disease, and increase the risk of lymphoma. It is more likely to be misdiagnosed as other diseases. ALPS should be suspected in the case of chronic lymphadenopathy, splenomegaly and autoimmune features. Flow cytometry approach is helpful for the diagnosis. Immunosuppressive drugs are the necessary treatment. PMID- 26679670 TI - [Systemic necrotizing vasculitis presenting as gangrene combined with diabetes insipidus: a case report]. AB - The male patient reported here presented as gangrene and central diabetes insipidus (CDI), who had characteristics of vasculitis. The patient complained about polydipsia and polyuria half a year ago, and then developed tingling, pain and blackish discoloration of some fingers and toes 3 month ago. He also had Raynaud's phenomenon. After admission, his laboratory examination showed the rise of erythrocyte sedimentation rate, C-reactive protein, immunoglobulin, beta2 glycoprotein I and the activity of rheumatoid factors, lupus anticoagulant test. his pituitary gland showed loss of posterior signal on magnetic resonance imaging. In addition, his vasopressin test was active. However, there was no sufficient evidence to diagnose any specific disease; as a consequence the patient was diagnosed as idiopathic systemic necrotizing vasculitis (SNV). For SNV, the patient was treated with glucocorticoid 40 mg/d and impact therapy of cyclophosphamide 0.4 g every 2 weeks. He also received symptomatic treatment for gangrene and CDI. Cutaneous involvement leading to gangrene was widely reported in SNV, however pituitary involvement in SNV leading to CDI was rare. The prognosis of this patient was poor. PMID- 26679671 TI - [Perioperative management of abdominal aortic balloon occlusion in patients complicated with placenta percteta: a case report]. AB - When placenta previa complicated with placenta percreta, the exposure of operative field is difficult and the routine methods are difficult to effectively control the bleeding, even causing life-threatening results. A 31-year-old woman, who had been diagnosed with a complete type of placenta previa and placenta percreta with bladder invasion at 34 weeks gestation. Her ultrasound results showed a complete type of placenta previa and there was a loss of the decidual interface between the placenta and the myometrium on the lower part of the uterus, suggestive of placenta increta. For further evaluation of the placenta, pelvis magnetic resonance imaging was performed, which revealed findings suspicious of a placenta percreta. She underwent elective cecarean section at 36 weeks of gestation. Firstly, two ureteral stents were placed into the bilateral ureter through the cystoscope. After the infrarenal abdominal aorta catheter was inserted via the femoral artery (9 F sheath ), subarachnoid anesthesia had been established. A healthy 2 510 g infant was delivered, with Apgar scores of 10 at 1 min and 10 at 5 min. Immediately after the baby was delivered, following which there was massive haemorrhage and general anaesthesia was induced. The balloon catheter was immediately inflated until the wave of dorsal artery disappeared. With the placenta retained within the uterus, a total hysterectomy was performed. The occluding time was 30 min. The intraoperative blood loss was 2 500 mL. The occluding balloon was deflated at the end of the operation. The patient had stable vital signs and normal laboratory findings during the recovery period and the hemoglobin was 116 g/L. She was discharged six days after delivery without intervention-related complications. This case illustrates that temporary occlusion of the infrarenal abdominal aorta using balloon might be a safe and effective treatment option for patients with placenta previa complicated with placenta percreta, who were at high risk for peripartum hemorrhage. Early removal of the endovascular catheter and close postoperative surveillance of the vascular system are required with this procedure to minimize the risk of vascular complications. However, further studies are needed to determine whether the potential benefits of temporary occlusion of the infrarenal abdominal aorta using balloon outweigh the potential risks. PMID- 26679672 TI - [Myoclonus epilepsy with ragged-red fibers: a case report and literature review]. AB - To demonstrate the clinical manifestation, diagnosis and treatment of myoclonus epilepsy with ragged-red-fibers (MERRF), a case of MERRF was presented with review of the literature. A 4-year-7-month-old girl was diagnosed with MERRF. She had tremor, fatigue and developmental delay for more than 2 years. Laboratory tests showed that the serum and urine lactic acid and pyruvic acid increased significantly. Electroencephalogram showed diffuse and focal spike slow wave and slow wave in right central and parietal regions. Electromyogram showed neurological damage. Gene mutational analysis showed mtDNA 8344 A>G mutation. The mutational rate was 78%. Mitochondrial disease MERRF syndrome was diagnosed. Cocktails therapy with vitamins B1, B6, B12, L-carnitine, and coenzyme Q10 was administrated to the patient. MERRF is a rare disease. The diagnosis can be made by gene mutational analysis. Cocktail therapy may slow down the deterioration of the disease. Gene therapy is still experimental. PMID- 26679673 TI - [Peri-operation treatment for patients with hemophilia A in children with intracranial malignant tumor: a report of 2 cases]. AB - Hemophilia A is aninherited bleeding disorder, lack of coagulation factor VIII (FVIII), and if combined with intracranial malignant tumor, the operation risk is very high. Department of Pediatric Surgery in Peking University First Hospital used coagulation factor replacement therapy, succeeded in the operation of 2 cases of intracranial malignant tumor with hemophilia A in children, with no abnormal bleeding events. The establishment of the multi subject cooperation group before operation, good preoperative preparation, enough alternative factors, and close postoperative monitoring, are the key to the successful treatment. PMID- 26679674 TI - [Tuberculous prostatic abscess following intravesical bacillus Calmette-Guerin immunotherapy: a case report]. AB - Intravesical bacillus Calmette-Guerin (BCG) was a common treatment for non-muscle invasive urothelial carcinoma of the bladder. The complication of prostatic abscess was rare. We reported a case of tuberculous prostatic abscess after BCG therapy. A 65-year-old man was diagnosed as bladder cancer and accepted transurethral resection of bladder tumor (TURBT) treatment. He received a 6-week induction course without any infection complication. Following the second BCG maintenance instillation, he complained of fever and dysuria. Transrectal ultrasound (TRUS) demonstrated a well-defined complex mass in the right lobe of his prostate. The diagnosis of tuberculous prostatic abscess was considered after excluding other bacterial infection. The patient was treated with an anti tuberculous regimen of isoniazid, rifampicin, and ethambutol. The symptoms were relieved after 4 weeks of anti-tuberculous therapy. Because of the good response to the medicine, no further aspiration or drainage of prostatic abscess was carried out. The anti-tuberculous therapy had to be stopped for serious drug induced liver injury after 6 weeks of anti-tuberculous therapy. Eight weeks later of stopping anti-tuberculous therapy, the follow-up TRUS showed the disappearance of the prostatic abscess and the test of his liver function was normal. Considering the virulence of BCG is weaker than that of common tuberclebacillus, the shorter course of anti-tuberculous therapy maybe an alternative choice, and surgical drainage is not always necessary. PMID- 26679675 TI - Diarylheptanoids from Alnus nepalensis attenuates LPS-induced inflammation in macrophages and endotoxic shock in mice. AB - Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-alpha and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases. PMID- 26679676 TI - Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats. AB - Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF 1alpha), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1alpha), transforming growth factor- beta1 (TGF-beta1()), tumor necrosis factor-alpha (TNF-alpha) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1beta) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF 1alpha, VEGF, SDF-1alpha, TGF-beta1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-alpha and the mRNA of IL-1beta and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. PMID- 26679677 TI - The anti-inflammatory effect of TR6 on LPS-induced mastitis in mice. AB - [TRIAP]-derived decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRIAP-derived decoy peptide (TR6) containing, the N-terminal portion of the third helical region of the [TIRAP] TIR domain (sequence "N" RQIKIWFQNRRMKWK and -KPGFLRDPWCKYQML-"C"). We evaluated the effects of TR6 on lipopolysaccharide-induced mastitis in mice. In vivo, the mastitis model was induced by LPS administration for 24h, and TR6 treatment was initiated 1h before or after induction of LPS. In vitro, primary mouse mammary epithelial cells and neutrophils were used to investigate the effects of TR6 on LPS-induced inflammatory responses. The results showed that TR6 significantly inhibited mammary gland hisopathologic changes, MPO activity, and LPS-induced production of TNF-alpha, IL-1beta and IL-6. In vitro, TR6 significantly inhibited LPS-induced TNF-alpha and IL-6 production and phosphorylation of NF-kappaB and MAPKs. In conclusion, this study demonstrated that the anti-inflammatory effect of TR6 against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-kappaB and MAPK signaling pathways. TR6 may be a promising therapeutic reagent for mastitis treatment. PMID- 26679678 TI - Icariin attenuates cerebral ischemia-reperfusion injury through inhibition of inflammatory response mediated by NF-kappaB, PPARalpha and PPARgamma in rats. AB - Icariin (ICA), an active flavonoid extracted from Chinese medicinal herb Epimedii, has been reported to exhibit many pharmacological effects including alleviating brain injury. However, little is known about the protection of ICA on ischemic stroke. Hence, this study was designed to investigate the neuroprotective effect of ICA and explore its underlying mechanisms on ischemic stroke induced by cerebral ischemia-reperfusion (I/R) injury in rats. The animals were pretreated with ICA at doses of 10, 30mg/kg twice per day for 3 consecutive days followed by cerebral I/R injury induced by middle cerebral artery occlusion (MCAO) for 2h and reperfusion for 24h. Neurological function and infarct volume were observed at 24h after reperfusion, the protein expression levels of interleukin-1beta (IL-1beta), transforming growth factor-beta1 (TGF-beta1), PPARalpha and PPARgamma, inhibitory kappaB-alpha (IkappaB-alpha) degradation and nuclear factor kappaB (NF-kappaB) p65 phosphorylation were detected by Western blot, respectively. It was found that pretreatment with ICA could decrease neurological deficit score, diminish the infarct volume, and reduce the protein levels of IL-1beta and TGF-beta1. Moreover, ICA suppressed IkappaB-alpha degradation and NF-kappaB activation induced by I/R. Furthermore, the present study also showed that ICA up-regulated PPARalpha and PPARgamma protein levels. These findings suggest that ICA has neuroprotective effect on ischemic stroke in rats through inhibition of inflammatory responses mediated by NF-kappaB and PPARalpha and PPARgamma. PMID- 26679679 TI - Comparison Between Percutaneous Transhepatic Rigid Cholangioscopic Lithotripsy and Conventional Percutaneous Transhepatic Cholangioscopic Surgery for Hepatolithiasis Treatment. AB - BACKGROUND: Percutaneous transhepatic cholangioscopy (PTCS) is one option for treating hepatolithiasis without surgical resection. This approach can use conventional biliary drainage methods over a long period, but a shorter procedure needs to be evolved. OBJECTIVE: To evaluate the short-term and the long-term therapeutic outcomes of percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) in comparison with conventional PTCS. METHODS: In this retrospective study, 118 patients with hepatolithiasis were enrolled who underwent treatment in our hospital between March 2007 and July 2014. About 67 of them received PTCSL and the remaining 51 patients received conventional PTCS. Preoperative data, surgical operation-related records, the postoperative therapeutic effect, and the long-term hepatolithiasis recurrence rate were collected for comparison between the 2 groups. RESULTS: The age, sex, and surgical history were similar between the 2 groups, but there was a significant difference in the Child-Pugh score, with more grade 3 patients in the PTCS group (P=0.002). However, the operation time, intraoperative blood infusion, and the blood loss were similar between the 2 groups. The final clearance ratio of calculus in the PTCSL group was significantly better than in the PTCS group after multivariate analysis (P=0.021; OR=0.201; 95% CI, 0.051-0.785). Calculus recurrence was 9% (PTCSL) and 22% (PTCS). The postoperative hospital stay was significantly shorter in the PTCSL group (P=0.001; OR=1.337; 95% CI, 1.132-1.58). CONCLUSIONS: PTCSL was a satisfactory therapeutic option for hepatolithiasis treatment, with less operation time and a superior long-term therapeutic effect compared with conventional PTCS. PMID- 26679680 TI - Perioperative Continuous Ropivacaine Wound Infusion in Laparoscopic Cholecystectomy: A Randomized Controlled Double-blind Trial. AB - Wound infusion with local anesthetics has been used for postoperative pain relief with variable results. This randomized, controlled, double-blind clinical trial examines the effect of ropivacaine infusion on pain after laparoscopic cholecystectomy. A total of 110 patients were randomly assigned to 2 groups. After induction of anesthesia a 75-mm catheter was inserted subcutaneously and connected to an elastomeric pump containing either 0.75% ropivacaine (ropivacaine group) or normal saline (control group) for 24 hours postoperatively. Before skin closure, each hole was infiltrated with 2 mL of 0.75% ropivacaine or normal saline according to randomization. Pain at rest, pain during cough, and analgesic consumption were recorded in the postanesthesia care unit and at 2, 4, 8, 24, and 48 hours postoperatively. Analgesic requirements and pain scores were recorded 1 and 3 months after surgery. The ropivacaine group reported less pain during cough (P=0.044) in the postanesthesia care unit (P=0.017) and 4 hours postoperatively (P=0.038). Ropivacaine wound infusion had no effect on late and chronic pain. PMID- 26679681 TI - Increased Caseload Volume is Associated With Better Oncologic Outcomes After Laparoscopic Resections for Colorectal Cancer. AB - PURPOSE: To evaluate the impact of caseload volume on the outcomes of open and laparoscopic surgery for colorectal cancer. METHODS: Between April 1999 and January 2011, patients who underwent open or laparoscopic resection for colorectal adenocarcinoma with curative intent were identified. There were 2 groups of surgeons, whose primary practice is gastrointestinal surgery (n=5, group A) and general surgery (n=14, group B). Histopathologic and oncologic outcomes, as well as survival data were evaluated. RESULTS: A total of 815 patients fulfilled the study criteria and 356 (group A: 120, group B: 236) patients who had >2 years' follow-up data were included. Colorectal procedures constituted 33% and 19% of all the operations in A and B groups, respectively (P<0.0001). Among the colorectal cases, rates of laparoscopic surgery were 37% and 20% in the group A and B, respectively (P<0.0001). Practice pattern was independently associated with better overall survival and was favoring the group A (P=0.02). CONCLUSIONS: Increased caseload volume improves oncologic outcomes in patients undergoing colorectal resection for nonmetastatic cancer. PMID- 26679682 TI - Colonoscopic Perforations, What is Our Experience in a Training Hospital? AB - The aim of this study was to describe our experience in patients treated with the diagnosis of colonoscopic perforation. A retrospective institutional computer based search of the patients treated with the diagnosis of colonoscopic perforation between July 2009 and May 2014 was undertaken. Our study included 16 patients. In 9 (56%) patients, perforations occurred during the diagnostic colonoscopy. Snare polypectomy was the causative factor in 5 patients associated with therapeutic colonoscopy. The perforation was significantly higher in patients who underwent therapeutic colonoscopy than those had diagnostic colonoscopy (P<0.007). The sigmoid colon was the most common perforation site (62.5%). Twelve patients (75%) were treated by surgically, 3 (19%) patients by conservatively, and 1 (6%) by endoscopic clipping. Early recognition of the perforation is critical. Therefore, a high index of suspicion is essential for the prompt and accurate diagnosis. PMID- 26679683 TI - Minimally Invasive Esophagectomy in the Lateral-prone Position: Experience of 226 Cases. AB - BACKGROUND: An open esophagectomy for esophageal cancer is a severely invasive procedure. Minimally invasive esophagectomy (MIE) has emerged as an effective alternative to open techniques. Conventionally, a thoracoscopic procedure is performed either in the left lateral decubitus position or in the prone position. Both positions have their disadvantage during the mobilization of the esophagus. In this study, we applied a novel position: the left lateral-prone position in the throacoscopic phase of MIE; we also describe the details of the technique and its feasibility, and present the initial results of this large-volume series. METHOD: We performed 226 cases of MIEs for esophageal cancer successfully from February 2008 to September 2014. All patients received thoracoscopic mobilization of the esophagus, followed by larparoscopic mobilization of the stomach and cervical anastomosis (McKeown or 3-field lymphadenectomy dissection esophagectomy). The throacoscopic part was performed in the left lateral-prone position. Perioperative data and the surgical outcome were studied retrospectively. RESULT: Of the 226 patients, 131 were men (57.9%) and 95 (42.1%) were women, with a median age of 64.5 years. All procedures were completed by thoracoscopy and laparoscopy, except 3 cases of conversion to open thoracotomy and 2 conversions to open laparotomy. Two-field lymphadenectomy was performed in 89 patients. Three-field lymphadenectomy was performed in 137 patients. Only 6 (2.7%) patients required blood transfusion. Postoperative morbidity was encountered in 78 (34.5%) patients, and anastomotic leak occurred in 9 cases (4.0%). Vocal cord paralysis was found in 11 cases (4.9%). The mean number of lymph nodes harvested was 21. The 30-day postoperative mortality rate was 1.3% (n=3). The mean length of hospital stay was 12.7 days. CONCLUSIONS: MIE in the lateral-prone position is technically less demanding and provides better technical safety, with good oncological effectiveness. This positioning is a feasible and appropriate alternative for minimally invasive surgery of esophageal carcinoma. PMID- 26679684 TI - Late Complications After Endoscopic Sphincterotomy. AB - The introduction of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (ES) has changed the treatment of choledocholithiasis. An increasing number of young patients are requiring ES, and this raises concern regarding any potential long-term complications arising from irreversibly altering the anatomy of the sphincter of Oddi. In particular, concern has been raised regarding the risk of late cholangiocarcioma. A review was performed evaluating the relationship between ES for benign disease and the subsequent development of late complications, including biliary tract malignancy, the formation of primary duct stones, and recurring cholangitis. A systematic review of articles published between 1970 and 2013 was undertaken. Current evidence shows that ES is a safe and effective treatment for common bile duct stones. The long-term risk of subsequent cholangiocarcinoma has not been convincingly proven although in many of these studies the follow-up period was inadequate. There does appear to be an associated increased incidence of cholangiocarcinomas following sphincterotomy although this is not proven to be causative. If there is an increased risk of cholangiocarcinoma following ES, it is likely to be small in western populations. However, until longer follow-up studies are published, it may be prudent to avoid ES in the very young. PMID- 26679685 TI - Long-term Survival of Patients With Endoscopic Submucosal Dissection for Remnant Gastric Cancers. AB - PURPOSE: The aim of this study was to compare the oncologic results of endoscopic submucosal dissection (ESD) for early gastric cancers (EGC) in remnant stomachs (RS) with results of ESD for EGC in normal stomachs (NS). METHODS: From 2002 to 2013, ESD was performed for 583 EGC lesions. ESD of the RS was performed for 34 lesions. RESULTS: Two patients with EGC in the NS and 1 patient with EGC in the RS died from these gastric cancers. In all patients, the ESD treatments were considered outside of indications according to the pathologic results. The 5-year cause-specific survival rate was 99.5% for EGC patients with NS and 96.2% for EGC patients with RS. The 5-year overall survival rates were 88.4% for patients with NS and 58.4% for patients with RS. CONCLUSIONS: On the basis of the favorable long-term oncologic outcomes, ESD for EGC in the RS can be considered feasible in clinical practice. PMID- 26679686 TI - Clinical Significance of Closure of Mesenteric Defects in Laparoscopic Colectomy: A Single-Institutional Cohort Study. AB - BACKGROUND: The effect of closure of mesenteric defects to prevent complications, such as internal hernia, during laparoscopic colectomy remains controversial and is a subject of debate. PURPOSE: This retrospective single-institution study aimed to clarify the clinical significance of mesenteric defect closure during a laparoscopic colectomy. METHODS: We evaluated 58 patients who underwent laparoscopic right-side colectomy or transverse colectomy. The statistical relevance of complications, surgical maneuvers, and clinical factors was examined. RESULTS: The mesenteric defects were closed in 30 patients and not closed in 28 patients. Two patients with ileus and 1 with a deep incisional surgical site infection required a second surgery. The reoperation rate was significantly higher in the nonclosure group than in the closure group (11% vs. 0%, respectively; P=0.033). CONSIDERATION: Serious complications requiring reoperation occurred only in the nonclosure group. The procedure for closing the defect did not extend the operation time or increase the bleeding. PMID- 26679687 TI - Comparing the risk of tardive dyskinesia in older adults with first-generation and second-generation antipsychotics: a systematic review and meta-analysis. AB - OBJECTIVE: The advent of second-generation antipsychotics (SGAs) in the 1990s brought optimism that neuroleptic-induced tardive dyskinesia (TD) may become relegated to history. Whether or not this is the case remains inconclusive, and this review aims to compare the risk of TD in older adults treated with first generation antipsychotics (FGAs) versus SGAs. METHODS: Relevant papers were sourced via a range of electronic databases, with a date range from 1957 to January 2015. Included studies used both a validated rating scale and research diagnostic criteria to report on the prevalence or incidence of TD in older adults exposed to antipsychotic medications. RESULTS: For FGAs, the prevalence estimate was 53% (95% confidence interval [CI] [39.0, 68.4]) for mild TD and 38% (95% CI [25.9, 50.3]) for probable TD. Incidence estimates for probable TD with FGAs were 23% (95% CI [15.3, 30.6]) at 1 year, 42% (95% CI [24.8, 58.4]) at 2 years and 57% (95% CI [45.3, 69.1]) at 3 years. For SGAs, the incidence estimates at 1 year were 7% (95% CI [4.4, 10.2]) for probable TD and 3% (95% CI [1.5, 4.2]) for persistent TD. CONCLUSIONS: The risk of probable TD is more than three times lower in older adults receiving SGAs in comparison with FGAs after 1 year of treatment (23% vs 7%). The risk of persistent TD at 1 year with SGAs is particularly low. Evidence is lacking in regard to the longer-term risk of TD with SGAs, although the rates associated with the prolonged use of FGAs are high. Caution is therefore still required, particularly with the protracted use of both FGAs and SGAs. PMID- 26679689 TI - Quantifying the response of structural complexity and community composition to environmental change in marine communities. AB - Habitat structural complexity is a key factor shaping marine communities. However, accurate methods for quantifying structural complexity underwater are currently lacking. Loss of structural complexity is linked to ecosystem declines in biodiversity and resilience. We developed new methods using underwater stereo imagery spanning 4 years (2010-2013) to reconstruct 3D models of coral reef areas and quantified both structural complexity at two spatial resolutions (2.5 and 25 cm) and benthic community composition to characterize changes after an unprecedented thermal anomaly on the west coast of Australia in 2011. Structural complexity increased at both resolutions in quadrats (4 m(2)) that bleached, but not those that did not bleach. Changes in complexity were driven by species specific responses to warming, highlighting the importance of identifying small scale dynamics to disentangle ecological responses to disturbance. We demonstrate an effective, repeatable method for quantifying the relationship among community composition, structural complexity and ocean warming, improving predictions of the response of marine ecosystems to environmental change. PMID- 26679690 TI - Genome-wide analysis of tomato long non-coding RNAs and identification as endogenous target mimic for microRNA in response to TYLCV infection. AB - Recently, a large number of long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes in animals and plants. However, how lncRNAs function during plant DNA virus infection is largely unknown. We performed strand-specific paired-end RNA sequencing of tomato samples infected with Tomato yellow leaf curl virus (TYLCV) with three biological replicates. Overall, we predicted 1565 lncRNAs including long intergenic ncRNAs (lincRNAs) and natural antisense transcripts (lncNATs) and definitively identified lnRNAs that are involved in TYLCV infection by virus-induced gene silencing (VIGS). We also verified the functions of a set of lncRNAs that were differentially expressed between 0 and 7 days post inoculation (dpi). More importantly, we found that several lncRNAs acted as competing endogenous target mimics (eTMs) for tomato microRNAs involved in the TYLCV infection. These results provide new insight into lncRNAs involved in the response to TYLCV infection that are important components of the TYLCV network in tomatoes. PMID- 26679691 TI - Is the era of intravenous proton pump inhibitors coming to an end in patients with bleeding peptic ulcers? Meta-analysis of the published literature. AB - AIMS: Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed. RESULTS: A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I(2) = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI: 0.29, 2.71; P = 0.82; I(2) = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI: -0.39, 0.12; P = 0.29; I(2) = 32%) and -0.60 (95% CI: -1.42, 0.23; P = 0.16; I(2) = 79%), respectively. CONCLUSIONS: Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients. PMID- 26679692 TI - A Modest Protective Effect of Thyrotropin against Bone Loss Is Associated with Plasma Triiodothyronine Levels. AB - BACKGROUND: The independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD). METHODS: We conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip. RESULTS: Levels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5-200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels. CONCLUSIONS: The variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range. PMID- 26679693 TI - Carbon nanotube anions for the preparation of gold nanoparticle-nanocarbon hybrids. AB - Gold nanoparticles (AuNPs) can be evenly deposited on single-walled carbon nanotubes (SWCNTs) via the reduction of the highly stable complex, chloro(triphenylphosphine) gold(I), with SWCNT anions ('nanotubides'). This methodology highlights the unusual chemistry of nanotubides and provides a blueprint for the generation of many other hybrid nanomaterials. PMID- 26679695 TI - Effect of acute nitrate ingestion on central hemodynamic load in hypoxia. AB - Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown. PURPOSE: Investigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia. METHODS: 20 Healthy men (23 +/- 3 yrs, BMI 24.6 +/- 2.8 kg m(-2)) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 +/- 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio. RESULTS: Aortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05). CONCLUSIONS: Acute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia. PMID- 26679694 TI - Survivin contributes to DNA repair by homologous recombination in breast cancer cells. AB - Survivin overexpression, frequently found in breast cancers and others, is associated with poor prognosis. Its dual regulation of cell division and apoptosis makes it an attractive therapeutic target but its exact functions that are required for tumor maintenance are still elusive. Survivin protects cancer cells from genotoxic agents and this ability is generally assigned to a universal anti-apoptotic function. However, a specific role in cancer cell protection from DNA damage has been overlooked so far. We assessed DNA damage occurrence in Survivin-depleted breast cancer cells using gammaH2AX staining and comete assay. QPCR data and a gene conversion assay indicated that homologous recombination (HR) was impaired upon Survivin depletion. We conducted the analysis of Survivin and HR genes' expression in breast tumors. We revealed BRCAness phenotype of Survivin-depleted cells using cell death assays combined to PARP targeting. Survivin silencing leads to DNA double-strand breaks in breast cancer cells and functionally reduces HR. Survivin depletion decreases the transcription of a set of genes involved in HR, decreases RAD51 protein expression and impairs the endonuclease complex MUS81/EME1 involved in the resolution of Holliday junctions. Clinically, EME1, RAD51, EXO1, BLM expressions correlate with that of BIRC5 (coding for Survivin) and are of prognostic value. Functionally, Survivin depletion triggers p53 activation and sensitizes cancer cells to of PARP inhibition. We defined Survivin as a constitutive actor of HR in breast cancers, and implies that its inhibition would enhance cell vulnerability upon PARP inhibition. PMID- 26679696 TI - Early versus late enteral feeding in critically ill children: a randomized controlled trial. PMID- 26679697 TI - Venous-to-arterial carbon dioxide difference: an experimental model or a bedside clinical tool? PMID- 26679699 TI - Shifting Milestones of Natural Sciences: The Ancient Egyptian Discovery of Algol's Period Confirmed. AB - The Ancient Egyptians wrote Calendars of Lucky and Unlucky Days that assigned astronomically influenced prognoses for each day of the year. The best preserved of these calendars is the Cairo Calendar (hereafter CC) dated to 1244-1163 B.C. We have presented evidence that the 2.85 days period in the lucky prognoses of CC is equal to that of the eclipsing binary Algol during this historical era. We wanted to find out the vocabulary that represents Algol in the mythological texts of CC. Here we show that Algol was represented as Horus and thus signified both divinity and kingship. The texts describing the actions of Horus are consistent with the course of events witnessed by any naked eye observer of Algol. These descriptions support our claim that CC is the oldest preserved historical document of the discovery of a variable star. The period of the Moon, 29.6 days, has also been discovered in CC. We show that the actions of Seth were connected to this period, which also strongly regulated the times described as lucky for Heaven and for Earth. Now, for the first time, periodicity is discovered in the descriptions of the days in CC. Unlike many previous attempts to uncover the reasoning behind the myths of individual days, we discover the actual rules in the appearance and behaviour of deities during the whole year. PMID- 26679698 TI - Chronic widespread pain is associated with worsening frailty in European men. AB - BACKGROUND: we hypothesised that chronic widespread pain (CWP), by acting as a potential stressor, may predispose to the development of, or worsening, frailty. SETTING: longitudinal analysis within the European Male Ageing Study (EMAS). PARTICIPANTS: a total of 2,736 community-dwelling men aged 40-79. METHODS: subjects completed a pain questionnaire and shaded a manikin, with the presence of CWP defined using the American College of Rheumatology criteria. Physical activity, smoking, alcohol consumption and depression were measured. Repeat assessments took place a median of 4.3 years later. A frailty index (FI) was used, with frail defined as an FI >0.35. The association between CWP at baseline and the new occurrence of frailty was examined using logistic regression; the association between CWP at baseline and change in FI was examined using negative binomial regression. RESULTS: at baseline, 218 (8.3%) men reported CWP. Of the 2,631 men who were defined as non-frail at baseline, 112 (4.3%) were frail at follow-up; their mean FI was 0.12 (SD 0.1) at baseline and 0.15 (SD 0.1) at follow-up, with a mean change of 0.03 (SD 0.08) P <= 0.001. Among men who were non-frail at baseline, those with CWP were significantly more likely to develop frailty. After adjustment for age and centre, compared with those with no pain, those with CWP at baseline had a 70% higher FI at follow-up; these associations remained significant after further adjustment for smoking, body mass index, depression, physical activity and FI at baseline. CONCLUSION: the presence of CWP is associated with an increased risk of frailty in older European men. PMID- 26679700 TI - Vulnerability to climate warming of Liolaemus pictus (Squamata, Liolaemidae), a lizard from the cold temperate climate in Patagonia, Argentina. AB - The vulnerability of populations and species to global warming depends not only on the environmental temperatures, but also on the behavioral and physiological abilities to respond to these changes. In this sense, the knowledge of an organism's sensitivity to temperature variation is essential to predict potential responses to climate warming. In particular, it is interesting to know how close species are to their thermal limits in nature and whether physiological plasticity is a potential short-term response to warming climates. We exposed Liolaemus pictus lizards, from northern Patagonia, to either 21 or 31 degrees C for 30 days to compare the effects of these treatments on thermal sensitivity in 1 and 0.2 m runs, preferred body temperature (T pref), panting threshold (T pant), and critical minimum temperature (CTMin). Furthermore, we measured the availability of thermal microenvironments (operative temperatures; T e) to measure how close L. pictus is, in nature, to its optimal locomotor performance (T o) and thermal limits. L. pictus showed limited physiological plasticity, since the acclimation temperature (21 and 31 degrees C) did not affect the locomotor performance nor did it affect T pref, the T pant, or the CTMin. The mean T e was close to T o and was 17 degrees C lower than the CTMax. The results suggest that L. pictus, in a climate change scenario, could be vulnerable to the predicted temperature increment, as this species currently lives in an environment with temperatures close to their highest locomotor temperature threshold, and because they showed limited acclimation capacity to adjust to new thermal conditions by physiological plasticity. Nevertheless, L. pictus can run at 80 % or faster of its maximum speed across a wide range of temperatures near T o, an ability which would attenuate the impact of global warming. PMID- 26679701 TI - Risk factors of hypertension among adults aged 35-64 years living in an urban slum Nairobi, Kenya. AB - BACKGROUND: Hypertension is an emerging public health problem in Sub Saharan Africa (SSA) and urbanization is considered to favor its emergence. Given a paucity of information on hypertension and associated risk factors among urban slum dwellers in SSA, we aimed to characterize the distribution of risk factors for hypertension and investigate their association with hypertension in an urban slum in Kenya. METHODS: We conducted a community based cross-sectional survey among adults 35 years and older living in Kibera slum Nairobi, Kenya. Trained interviewers collected data on socio demographic characteristics and self reported health behaviours using modified World Health Organization stepwise surveillance questionnaire for chronic disease risk factors. Anthropometric and blood pressure measurements were performed following standard procedures. Multiple logistic regression was used for analysis and odds ratios with 95 % confidence intervals were calculated to identify risk factors associated with hypertension. RESULT: A total of 1528 adults were surveyed with a mean age of 46.7 years. The age-standardized prevalence of hypertension was 29.4 % (95 % CI 27.0-31.7). Among the 418 participants classified as hypertensive, over one third (39.0 %) were unaware they had hypertension. Prevalence of current smoking and alcohol consumption was 8.5 and 13.1 % respectively. Over one quarter 26.2 % participants were classified as overweight (Body Mass Index [BMI] >=25 to <=29.9 kg/m(2)), and 17 % classified as obese (BMI >=30 kg/m(2)). Overweight, obesity, current smoking, some level of education, highest wealth index, moderate physical activity, older age and being widowed were each independently associated with hypertension. When fit in a multivariable logistic regression model, being a widow [AOR = 1.7; (95 % CI, 1.1-2.6)], belonging to the highest wealth index [AOR = 1.6; (95 % CI, 1.1-2.5)], obesity [AOR = 1.8; 95 % CI, 1.1-3.1)] and moderate physical activity [AOR = 1.9; (95 % CI, 1.2-3.0)], all remained significantly associated with hypertension. CONCLUSION: Hypertension in the slum is a public health problem affecting at least one in three adults aged 35-64 years. Age, marital status, wealth index, physical inactivity and body mass index are important risk factors associated with hypertension. Prevention measures targeting the modifiable risk factors associated with hypertension are warranted to curb hypertension and its progressive effects. PMID- 26679702 TI - Omega-3 Fatty Acid Supplementation for 12 Weeks Increases Resting and Exercise Metabolic Rate in Healthy Community-Dwelling Older Females. AB - Critical among the changes that occur with aging are decreases in muscle mass and metabolic rate and an increase in fat mass. These changes may predispose older adults to chronic disease and functional impairment; ultimately resulting in a decrease in the quality of life. Research has suggested that long chain omega-3 fatty acids, found predominantly in fatty fish, may assist in reducing these changes. The objective of this study was to evaluate the effect of fish oil (FO) supplementation in a cohort of healthy, community-dwelling older females on 1) metabolic rate and substrate oxidation at rest and during exercise; 2) resting blood pressure and resting and exercise heart rates; 3) body composition; 4) strength and physical function, and; 5) blood measures of insulin, glucose, c reactive protein, and triglycerides. Twenty-four females (66 +/- 1 yr) were recruited and randomly assigned to receive either 3g/d of EPA and DHA or a placebo (PL, olive oil) for 12 wk. Exercise measurements were taken before and after 12 wk of supplementation and resting metabolic measures were made before and at 6 and 12 wk of supplementation. The results demonstrated that FO supplementation significantly increased resting metabolic rate by 14%, energy expenditure during exercise by 10%, and the rate of fat oxidation during rest by 19% and during exercise by 27%. In addition, FO consumption lowered triglyceride levels by 29% and increased lean mass by 4% and functional capacity by 7%, while no changes occurred in the PL group. In conclusion, FO may be a strategy to improve age-related physical and metabolic changes in healthy older females. Trial registration: ClinicalTrials.gov NCT01734538. PMID- 26679703 TI - Better Fitness in Captive Cuvier's Gazelle despite Inbreeding Increase: Evidence of Purging? AB - Captive breeding of endangered species often aims at preserving genetic diversity and to avoid the harmful effects of inbreeding. However, deleterious alleles causing inbreeding depression can be purged when inbreeding persists over several generations. Despite its great importance both for evolutionary biology and for captive breeding programmes, few studies have addressed whether and to which extent purging may occur. Here we undertake a longitudinal study with the largest captive population of Cuvier's gazelle managed under a European Endangered Species Programme since 1975. Previous results in this population have shown that highly inbred mothers tend to produce more daughters, and this fact was used in 2006 to reach a more appropriate sex-ratio in this polygynous species by changing the pairing strategy (i.e., pairing some inbred females instead of keeping them as surplus individuals in the population). Here, by using studbook data we explore whether purging has occurred in the population by investigating whether after the change in pairing strategy a) inbreeding and homozygosity increased at the population level, b) fitness (survival) increased, and c) the relationship between inbreeding and juvenile survival, was positive. Consistent with the existence of purging, we found an increase in inbreeding coefficients, homozygosity and juvenile survival. In addition, we showed that in the course of the breeding programme the relationship between inbreeding and juvenile survival was not uniform but rather changed over time: it was negative in the early years, flat in the middle years and positive after the change in pairing strategy. We highlight that by allowing inbred individuals to mate in captive stocks we may favour sex-ratio bias towards females, a desirable managing strategy to reduce the surplus of males that force most zoos to use ethical culling and euthanizing management tools. We discuss these possibilities but also acknowledge that many other effects should be considered before implementing inbreeding and purging as elements in management decisions. PMID- 26679704 TI - Importance of Interaction between Integrin and Actin Cytoskeleton in Suspension Adaptation of CHO cells. AB - The biopharmaceutical production process relies upon mammalian cell technology where single cells proliferate in suspension in a chemically defined synthetic environment. This environment lacks exogenous growth factors, usually contributing to proliferation of fibroblastic cell types such as Chinese hamster ovary (CHO) cells. Use of CHO cells for production hence requires a lengthy 'adaptation' process to select clones capable of proliferation as single cells in suspension. The underlying molecular changes permitting proliferation in suspension are not known. Comparison of the non-suspension-adapted clone CHO-AD and a suspension-adapted propriety cell line CHO-SA by flow cytometric analysis revealed a highly variable bi-modal expression pattern for cell-to-cell contact proteins in contrast to the expression pattern seen for integrins. Those have a uni-modal expression on suspension and adherent cells. Integrins showed a conformation distinguished by regularly distributed clusters forming a sphere on the cell membrane of suspension-adapted cells. Actin cytoskeleton analysis revealed reorganisation from the typical fibrillar morphology found in adherent cells to an enforced spherical subcortical actin sheath in suspension cells. The uni-modal expression and specific clustering of integrins could be confirmed for CHO-S, another suspension cell line. Cytochalasin D treatment resulted in breakdown of the actin sheath and the sphere-like integrin conformation demonstrating the link between integrins and actin in suspension-adapted CHO cells. The data demonstrates the importance of signalling changes, leading to an integrin rearrangement on the cell surface, and the necessity of the reinforcement of the actin cytoskeleton for proliferation in suspension conditions. PMID- 26679705 TI - Roles of Triolein and Lipolytic Protein in the Pathogenesis and Survival of Mycobacterium tuberculosis: a Novel Therapeutic Approach. AB - Discovery of novel secreted enzymes and proteins in Mycobacterium tuberculosis (M. tuberculosis) are imperative to understanding the pathogenic system for pathogenesis requires attention. Till date, the groups of these secreted enzymes are not meaningfully characterized in terms of M. tuberculosis. In this way, cutinase, a small lipolytic protein, exists in both bacteria and fungi as well which have a potential catalytic activity. During our search, we have found a few genes of M. tuberculosis demonstrating a same significant lipase action as fungi Fusarium solani cutinase contain. Genome sequencing of M. tuberculosis uncover a lot of proteins, wherein (Rv1758, Rv1984c, Rv2301, Rv3451, Rv3452, Rv3724A, Rv3724B, and Rv3802c) genes have been noted which are exhibiting a cutinase-like activity and closely homologous to that of F. solani cutinase and having the ability to hydrolyze model substrates including p-nitrophenyl butyrate (p-PNB), cutin, triacylglycerols (TAGs), and triolein (TO), yet their biological significance in pathogenesis stays subtle and uncharacterized. In a basic perspective, the measure of cutinase expressed by M. tuberculosis and part of these small lipolytic enzymes in the pathologic discipline require thorough characterization. So, through focusing on cutinase-encoding genes in M. tuberculosis and their active catalytic motif could help to build up a novel therapeutic approach. PMID- 26679706 TI - Tyrosinase-Mediated Construction of a Silk Fibroin/Elastin Nanofiber Bioscaffold. AB - Elastin has characteristics of elasticity, biological activity, and mechanical stability. In the present work, tyrosinase-mediated construction of a bioscaffold with silk fibroin and elastin was carried out, aiming at developing a novel medical biomaterial. The efficiency of enzymatic oxidation of silk fibroin and the covalent reaction between fibroin and elastin were examined by spectrophotometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and size exclusion chromatography (SEC). The properties of composite air dried and nanofiber scaffolds were investigated. The results reveal that elastin was successfully bonded to silk fibroins, resulting in an increase in molecular weight of fibroin proteins. ATR-FTIR spectra indicated that tyrosinase treatment impacted the conformational structure of fibroin-based membrane. The thermal behaviors and mechanical properties of the tyrosinase-treated scaffolds were also improved compared with the untreated group. NIH/3T3 cells exhibited optimum densities when grown on the nanofiber scaffold, implying that the nanofiber scaffold has enhanced biocompatibility compared to the air-dried scaffold. A biological nanofiber scaffold constructed from tyrosinase-treated fibroin and elastin could potentially be utilized in biomedical applications. PMID- 26679707 TI - Reproductive Life Planning: A Cross-Sectional Study of What College Students Know and Believe. AB - Objectives The Centers for Disease Control and Prevention recommends a reproductive life plan (RLP) to promote individual responsibility for preconception health. The objectives of this study were to determine existing awareness of RLPs in a cohort of reproductive-age adults and to evaluate their knowledge level and beliefs about reproductive life planning. Methods We performed a cross-sectional survey study of adults ages 18-40 years old seeking care at the student health center of a large public university. Participation was voluntary. Survey responses were analyzed by age and gender. Results A total of 559 surveys were collected and analyzed. Only 24 % of participants had heard of an RLP although a majority (62.9 %) agreed that it is important to develop an RLP. Most respondents (85.4 %) preferred to receive information about reproductive life planning from a primary care provider or obstetrician gynecologist, while only 4.2 % of patients surveyed reported ever being actually asked about an RLP by their healthcare provider. Among those who agreed that an RLP was important, knowledge of specific aspects of an RLP was lacking. Conclusions In our cohort of reproductive-age adults, general health literacy regarding RLPs was poor. Most of the young adults who responded to our survey did not know what an RLP was and even fewer had ever discussed one with their health provider. PMID- 26679708 TI - Previous Adverse Infant Outcomes as Predictors of Preconception Care Use: An Analysis of the 2010 and 2012 Los Angeles Mommy and Baby (LAMB) Surveys. AB - Objectives This study aimed to understand the impact of a previous adverse infant outcome (AIO) on use of preconception care prior to a subsequent pregnancy. Methods Responses from the 2010 and 2012 Los Angeles Mommy and Baby Surveys were analyzed. Weighted multivariate logistic regression was employed to identify significant associations between having had a previous AIO (preterm delivery, low birth weight infant, stillbirth, or major birth defect) and receipt of preconception care prior to the most recent pregnancy. Select patient-level covariates were included: chronic disease, age, education level, race/ethnicity, country of birth, insurance status prior to pregnancy and pregnancy intent. Adjustment for missing responses was performed using multiple chained imputation. Results After controlling for covariates, having had a previous AIO was associated with an increased odds of having utilized preconception care in the most recent pregnancy (OR 1.237, p = 0.040). Per the final regression model, a woman reporting a previous AIO and an intended subsequent pregnancy had a 42.4 % likelihood of having used preconception care. Of these women, only 28.8 % reported doing so because of concern regarding a previous birth complication. Discussion Women reporting a previous AIO were more likely to have used preconception care in a subsequent pregnancy. The prevalence of preconception care utilization remained low overall. Pregnancy intent emerged as a strong secondary predictor; any concerted strategy to improve access to preconception care must include initiatives to help ensure that pregnancies are planned. PMID- 26679710 TI - The advantages of selecting cartridges with a 1.8 mm height for pulmonary stapling. AB - PURPOSES: The purpose of this study was to retrospectively analyze the complications arising from stapling of the pulmonary parenchyma and to determine the most appropriate cartridges to use for pulmonary stapling. METHODS: A retrospective multi-institutional review was conducted by the Central Japan Lung Cancer Surgery Study Group. We analyzed both EchelonTM (EC) and EndoGIATM (EGIA) staplers in this study. The stapling cartridges were classified into 3 colors according to the height of the beta loops: green (2.0 mm), gold (1.8 mm), and blue (1.5 mm). RESULTS: Stapling of the pulmonary parenchyma was performed 9016 times. The total number of complications related to stapling was 61 (0.68 %). These complications were mainly caused by stapler-tissue thickness mismatch (n = 30, 49.2 %) and tissue fragility (n = 27, 44.3 %). The number and rate of complications of the different cartridges were 19 and 0.63 % for EGIA blue, 25 and 0.94 % for EGIA green, 1 and 0.067 % for EC gold, 12 and 0.98 % for EC blue, and 4 and 0.64 % for EC green, respectively. Complications associated with stapling using EC gold cartridges occurred less frequently than with the other cartridges (p = 0.0022). CONCLUSION: The gold cartridge appears to cause the least complications and may therefore be the most appropriate cartridge for stapling the pulmonary parenchyma among the tested staplers. PMID- 26679709 TI - Innovative approaches for improving maternal and newborn health--A landscape analysis. AB - BACKGROUND: Essential interventions can improve maternal and newborn health (MNH) outcomes in low- and middle-income countries, but their implementation has been challenging. Innovative MNH approaches have the potential to accelerate progress and to lead to better health outcomes for women and newborns, but their added value to health systems remains incompletely understood. This study's aim was to analyze the landscape of innovative MNH approaches and related published evidence. METHODS: Systematic literature review and descriptive analysis based on the MNH continuum of care framework and the World Health Organization health system building blocks, analyzing the range and nature of currently published MNH approaches that are considered innovative. We used 11 databases (MedLine, Web of Science, CINAHL, Cochrane, Popline, BLDS, ELDIS, 3ie, CAB direct, WHO Global Health Library and WHOLIS) as data source and extracted data according to our study protocol. RESULTS: Most innovative approaches in MNH are iterations of existing interventions, modified for contexts in which they had not been applied previously. Many aim at the direct organization and delivery of maternal and newborn health services or are primarily health workforce interventions. Innovative approaches also include health technologies, interventions based on community ownership and participation, and novel models of financing and policy making. Rigorous randomized trials to assess innovative MNH approaches are rare; most evaluations are smaller pilot studies. Few studies assessed intervention effects on health outcomes or focused on equity in health care delivery. CONCLUSIONS: Future implementation and evaluation efforts need to assess innovations' effects on health outcomes and provide evidence on potential for scale-up, considering cost, feasibility, appropriateness, and acceptability. Measuring equity is an important aspect to identify and target population groups at risk of service inequity. Innovative MNH interventions will need innovative implementation, evaluation and scale-up strategies for their sustainable integration into health systems. PMID- 26679711 TI - Flagellin and GroEL mediates in vitro binding of an atypical enteropathogenic Escherichia coli to cellular fibronectin. AB - BACKGROUND: Enteropathogenic Escherichia coli (EPEC) is distinguished mainly by the presence of EPEC adherence factor plasmid (pEAF) in typical EPEC (tEPEC) and its absence in atypical EPEC (aEPEC). The initial adherence to the intestinal mucosa is complex and mediated by adhesins other than bundle-forming pilus, which is not produced by aEPEC. Extracellular matrix (ECM) proteins of eukaryotic cells are commonly recognized by bacterial adhesins. Therefore, binding to ECM proteins may facilitate colonization, invasion and/or signaling by intestinal pathogens. Previous studies from our group demonstrated that aEPEC O26:H11 (strain BA2103) showed high binding activity to fibronectin, not shared by its counterpart, aEPEC O26:HNM. RESULTS: In the present study, using mass spectrometry after fibronectin associated immunoprecipitation, two proteins, flagellin (50 kDa) and GroEL (52 kDa), were identified and BA2103 binding ability to fibronectin was inhibited in the presence of anti-H11 and anti-GroEL sera, but not by either naive rabbit or other unrelated sera. It was also observed that the presence of purified flagellin inhibits adhesion of BA2103 to cellular fibronectin in a dose-dependent manner. Additionally, BA2103 GroEL is similar to the same protein of uropathogenic E. coli. CONCLUSIONS: Our results suggest that flagellin may play a role in the in vitro interaction of BA2103 with cellular fibronectin, and GroEL can be an accessory protein in this process. PMID- 26679713 TI - Why do diets fail? An exploration of dieters' experiences using thematic analysis. AB - Previous research has drawn on theoretical models and clinical observations to develop propositions regarding the mechanisms of diet failure, with only one study examining it directly from the perspective of dieters themselves. Furthermore, research to date has failed to provide an empirically validated, multi-factorial model of diet failure, despite the issue being recognised as a complex and multifaceted one. This study extended on previous research by examining themes of diet failure from the perspective of dieters ( n = 22) and health professionals in the field ( n = 5). PMID- 26679712 TI - Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma. AB - To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P < 0.0001). Median overall survival (OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients (P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients (n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease. PMID- 26679714 TI - Predictors of change in sexual activity after cardiac diagnosis: Elements to inform sexual counseling. AB - Safely returning to sexual activity after being diagnosed with a cardiac condition is at the core of sexual counseling strategies. To further inform sexual counseling, this study examined changes in sexual activity before and after a cardiac diagnosis. Logistic analysis was used to suggest factors that can contribute to a change in sexual activity among cardiac patients. Reduced frequency in sexual activity after a cardiac diagnosis was influenced by greater sexual concerns and a history of smoking, as well as by education and employment status. These findings suggest that cardiac patients experiencing significant concerns about resuming sexual activity need added support through the mental health system. PMID- 26679715 TI - [Esophageal Atresia Repair - Can We Influence the Schedule?]. AB - The treatment of newborns with esophageal atresia (EA) and tracheoesophageal fistula (TEF) is associated with a great logistic effort. The aim of the presented study was to analyse the possibility to influence the time of surgery. MATERIAL AND METHOD: Data from 30 neonates with EA and TEF regarding the date and mode of birth, biometric data and preoperative acid-base and blood gas values were collected retrospectively. The newborns were divided into two subgroups: birth between Monday and Thursday ("week"), and birth from Friday to Sunday ("weekend"). RESULTS: We observed a seasonal peak of births in November/December. The rate of prenatal ultrasound detection of polyhydramnions was 40%. In 14 of 16 cases with Caesarean section, maternal or foetal problems predicted the date and mode of delivery. In both groups, most newborns had an unimpaired postnatal adaptation. There were no significant differences regarding biometry. Delivery at the weekend was associated with later surgical repair (second vs. first day of life). Repeated estimations of acid-base and blood gas parameters over a median time span of 13 hours revealed a stable situation with a trend to normalisation. DISCUSSION: The time of birth is multifactorial and, in most cases, can neither be predicted nor influenced. Stable respiratory and metabolic parameters in the majority of patients allow a surgical intervention within a limited time frame during the first days of life. CONCLUSION: As it is hardly possible to plan the surgical procedure, an experienced team as well as neonatal intensive care facilities and operation room access must be available throughout the week. PMID- 26679716 TI - [Saw Injuries to the Hand - Epidemiological Aspects]. AB - Background: No current studies regarding saw injuries have been published in German literature for quite some time. Despite awareness measures and safety instructions, saw accidents along with crush injuries are the most common causes of severe hand injuries. Approximately 12,000 circular saw injuries occur in Germany each year. Since professional providers have increased prices due to the rising energy costs and a wide range of different home appliance saws are available, increasing use has been made of portable circular saws in the do-it yourself market sector. Patients and methods: At our hospital, we evaluated the data of 51 male patients with saw injuries. The present study investigated factors that may contribute to accidents involving saws. Results: 80 % of the accidents occurred at home, usually on weekends or after work. 51 % of the accidents happened while patients cut firewood. In 84 % of the cases, an electric table saw was used. The majority of severe hand injuries were sustained with lower priced saws. Injuries occurred most frequently between 11 a. m. and 2 p. m., primarily with injuries to bones, tendons, blood vessels and nerves. Replantable amputations or partial amputations occured rarely. In 37 % of the patients, anatomical reconstruction using osteosynthesis and/or microsurgical techniques was performed successfully. Conclusions: Saw injuries to the hand are sustained almost exclusively by men. Serious injuries from low-priced table saws and due to the lack of protective covering are predominant. Preventive measures and mandatory training could reduce the number of saw injuries in the years to come. The results obtained by us largely confirm the data from previous publications. PMID- 26679717 TI - [Standardisation of the Initial Treatment of Severely Burned Patients: The Necessary Transfer of Concepts from Trauma Care]. AB - The initial treatment of severely burned patients remains a huge challenge for first responders in emergency services as well as emergency doctors who do not work in a centre for severe burn injuries. The reason for this is the low number of cases in developed countries and a lack of training concepts for the specific aspects of the initial treatment of severe burn injuries. Because of guidelines with limited evidence (S1, S2k) and a lack of structured treatment approaches, uncertainties with respect to initial treatment are still visible. Even within the professional societies and on international comparison, controversial aspects remain. In contrast, optimised and standardised procedures are available for the treatment of severely injured (trauma) patients, based on PHTLS(r) (Pre Hospital Trauma Life Support) for preclinical and ATLS(r) (Advanced Trauma Life Support) for in-hospital first aid. This article takes stock of the current structure of care and the relevant evidence for the initial treatment of severe burns. Also it discusses a possible transfer and further development of concepts for primary trauma care by all disciplines involved. Nine essential steps in the primary care of burned patients are identified and evaluated. The need for the introduction of a uniform treatment algorithm is illustrated. The treatment algorithm presented in this article addresses all first responders who are faced with initial treatment in the first 24 hours outside of burn centres. As an essential, new aspect, it offers a transfer and adaptation of concepts from trauma care to standardise the care of severely burned patients. PMID- 26679718 TI - Percentage of Gutta-percha Filled Areas in Canals Obturated with Cross-linked Gutta-percha Core-carrier Systems, Single-Cone and Lateral Compaction Technique. AB - INTRODUCTION: The aim of this study was to compare different obturation techniques in terms of the percentage of gutta-percha filled areas (PGFA), sealer filled areas (PSFA), and voids in straight root canals prepared with different instruments. METHODS: One hundred sixty extracted single-rooted mandibular premolars with straight canals were allocated into 10 groups (n = 16 teeth per group): A, manual instrumentation + lateral compaction (LC); B, Mtwo + GuttaFusion (GF); C, Mtwo + LC; D, Mtwo + single-cone (SC); E, Reciproc + GF; F, Reciproc + LC; G, Reciproc + SC; H, WaveOne + GuttaCore (GC); I, WaveOne + LC; and J, WaveOne + SC. Apical preparation was size 40 in all groups, and AH Plus was used as a sealer. The teeth were sectioned at 2, 4, 6, and 8 mm from the apex. The total area of each canal segment was measured, and the areas were converted to PGFA, PSFA, and voids. Data were subjected to the Kruskal-Wallis and post hoc Dunn tests. RESULTS: At the 2-mm level, no significant differences in terms of PGFA and PSFA were obtained (P > .05). At all other levels, canals filled with GC and GF produced significantly higher PGFA and significantly lower PSFA than all other groups (P < .05). At the 2-mm, 4-mm, and 6-mm levels, canals filled with GC and GF showed less voids than group A (P < .05). CONCLUSIONS: Under the conditions of this study, independent of the instrument used for canal preparation, GuttaCore and GuttaFusion produced very homogenous root canal fillings with high PGFA and a low incidence of voids. PMID- 26679719 TI - Prediction of In-hospital Mortality in Emergency Department Patients With Sepsis: A Local Big Data-Driven, Machine Learning Approach. AB - OBJECTIVES: Predictive analytics in emergency care has mostly been limited to the use of clinical decision rules (CDRs) in the form of simple heuristics and scoring systems. In the development of CDRs, limitations in analytic methods and concerns with usability have generally constrained models to a preselected small set of variables judged to be clinically relevant and to rules that are easily calculated. Furthermore, CDRs frequently suffer from questions of generalizability, take years to develop, and lack the ability to be updated as new information becomes available. Newer analytic and machine learning techniques capable of harnessing the large number of variables that are already available through electronic health records (EHRs) may better predict patient outcomes and facilitate automation and deployment within clinical decision support systems. In this proof-of-concept study, a local, big data-driven, machine learning approach is compared to existing CDRs and traditional analytic methods using the prediction of sepsis in-hospital mortality as the use case. METHODS: This was a retrospective study of adult ED visits admitted to the hospital meeting criteria for sepsis from October 2013 to October 2014. Sepsis was defined as meeting criteria for systemic inflammatory response syndrome with an infectious admitting diagnosis in the ED. ED visits were randomly partitioned into an 80%/20% split for training and validation. A random forest model (machine learning approach) was constructed using over 500 clinical variables from data available within the EHRs of four hospitals to predict in-hospital mortality. The machine learning prediction model was then compared to a classification and regression tree (CART) model, logistic regression model, and previously developed prediction tools on the validation data set using area under the receiver operating characteristic curve (AUC) and chi-square statistics. RESULTS: There were 5,278 visits among 4,676 unique patients who met criteria for sepsis. Of the 4,222 patients in the training group, 210 (5.0%) died during hospitalization, and of the 1,056 patients in the validation group, 50 (4.7%) died during hospitalization. The AUCs with 95% confidence intervals (CIs) for the different models were as follows: random forest model, 0.86 (95% CI = 0.82 to 0.90); CART model, 0.69 (95% CI = 0.62 to 0.77); logistic regression model, 0.76 (95% CI = 0.69 to 0.82); CURB-65, 0.73 (95% CI = 0.67 to 0.80); MEDS, 0.71 (95% CI = 0.63 to 0.77); and mREMS, 0.72 (95% CI = 0.65 to 0.79). The random forest model AUC was statistically different from all other models (p <= 0.003 for all comparisons). CONCLUSIONS: In this proof-of concept study, a local big data-driven, machine learning approach outperformed existing CDRs as well as traditional analytic techniques for predicting in hospital mortality of ED patients with sepsis. Future research should prospectively evaluate the effectiveness of this approach and whether it translates into improved clinical outcomes for high-risk sepsis patients. The methods developed serve as an example of a new model for predictive analytics in emergency care that can be automated, applied to other clinical outcomes of interest, and deployed in EHRs to enable locally relevant clinical predictions. PMID- 26679721 TI - Exciting new developments at the 5th International Symposium on Surface and Interface of Biomaterials. AB - Materials intended for use as implantable or diagnostic devices are required not only to display the required functional bulk properties but also have surface properties that elicit a desired biological response, and do so with high selectivity. The area of surface functionalization approaches and bioactive coatings for biomaterials and biomedical devices has been the subject of much research over several decades; yet, many challenges still remain to be solved. The 5th International Symposium on Surface and Interface of Biomaterials (ISSIB) held in Sydney (Australia) in April 2015 was an ideal forum to discuss the most recent developments in biomaterial surface modification, characterization, and evaluation of biological responses. The conference covered a range of topics including antimicrobial coatings, analysis of biomaterial surfaces and interfaces, biomolecules and cells at surfaces and interfaces, nanoparticles, functional coatings, patterned biomaterials, nanofabrication, bioreactors, and biosensors. In this special conference issue, the authors include papers that detail some of the highlights from the meeting. PMID- 26679720 TI - Minimal domain of bacterial phytochrome required for chromophore binding and fluorescence. AB - Fluorescent proteins (FP) are used to study various biological processes. Recently, a series of near-infrared (NIR) FPs based on bacterial phytochromes was developed. Finding ways to improve NIR FPs is becoming progressively important. By applying rational design and molecular evolution we have engineered R. palustris bacterial phytochrome into a single-domain NIR FP of 19.6 kDa, termed GAF-FP, which is 2-fold and 1.4-fold smaller than bacterial phytochrome-based NIR FPs and GFP-like proteins, respectively. Engineering of GAF-FP involved a substitution of 15% of its amino acids and a deletion of the knot structure. GAF FP covalently binds two tetrapyrrole chromophores, biliverdin (BV) and phycocyanobilin (PCB). With the BV chromophore GAF-FP absorbs at 635 nm and fluoresces at 670 nm. With the PCB chromophore GAF-FP becomes blue-shifted and absorbs at 625 nm and fluoresces at 657 nm. The GAF-FP structure has a high tolerance to small peptide insertions. The small size of GAF-FP and its additional absorbance band in the violet range has allowed for designing a chimeric protein with Renilla luciferase. The chimera exhibits efficient non radiative energy transfer from luciferase to GAF-FP, resulting in NIR bioluminescence. This study opens the way for engineering of small NIR FPs and NIR luciferases from bacterial phytochromes. PMID- 26679722 TI - Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis. AB - OBJECTIVE: Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC). MATERIALS AND METHODS: A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled. RESULTS: Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p = 0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p = 0.0014), and nocturnal diarrhoea in 28% versus 18% (p = 0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p = 0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients. CONCLUSIONS: Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation 'microscopic'. Our study confirms the strong association with coeliac disease. PMID- 26679724 TI - A computational functional genomics based self-limiting self-concentration mechanism of cell specialization as a biological role of jumping genes. AB - Specialization is ubiquitous in biological systems and its manifold mechanisms are active research topics. Although clearly adaptive, the way in which specialization of cells is realized remains incompletely understood as it requires the reshaping of a cell's genome to favor particular biological processes in the competition on a cell's functional capacity. Here, a self specialization mechanism is identified as a possible biological role of jumping genes, in particular LINE-1 retrotransposition. The mechanism is self-limiting and consistent with its evolutionary preservation despite its likely gene breaking effects. The scenario we studied was the need for a cell to process a longer exposition to an extraordinary situation, for example continuous exposure to the nociceptive input or the intake of addictive drugs. Both situations may evolve toward chronification. The mechanism involves competition within a gene set in which a subset of genes cooperating in particular biological processes. The subset carries a piece of information, consisting of the LINE-1 sequence, about the destruction of their functional competitor genes which are not involved in that process. During gene transcription, an active copy of LINE-1 is co transcribed. At a certain low probability, a subsequently transcribed and thus actually exposed gene can be rendered nonfunctional by LINE-1 retrotransposition in a relevant gene part. As retrotransposition needs time it is unlikely that LINE-1 retrotranspose into its own carrier gene. This reshapes the cell genome toward self-specializing of those biological processes that are carried out with a high number of LINE-1 containing genes. Self-termination of the mechanism is achieved by allowing LINE-1 to also occasionally jump into the coding region of itself, thus destroying the information about competitor destruction by successively decreasing the number of LINE-1 until the mechanism ceases. Employing a computational functional genomics approach, we demonstrate the biological plausibility in functional genomic datasets of potentially chronifying situations and interpret our results in relation to a biological mechanism of self-specialization of complex systems in response to a persistent challenge as met in chronifying traits. PMID- 26679725 TI - Evaluation of commercial chromogenic media for the detection of meticillin resistant Staphylococcus aureus. AB - BACKGROUND: Selective chromogenic media allowing one-step meticillin-resistant Staphylococcus aureus (MRSA) isolation and identification are widely used. However, the changing epidemiology of MRSA means that the suitability of these chromogenic media requires investigation. AIM: To evaluate the following chromogenic media - Colorex MRSA, MRSA Select II, ChromID MRSA, and MRSA Brilliance 2 - for the detection of divergent strain types. METHODS: We used a diverse collection of S. aureus, including strains harbouring the mecC gene, strains expressing varying levels of meticillin resistance, and isolates recovered from patient samples. FINDINGS: MRSA Select II, Colorex MRSA, and ChromID each grew at a density of 1.5 * 10(1)cfu/mL for each SCCmec type investigated. Brilliance 2 demonstrated growth at 1.5 * 10(1)cfu/mL for mecC MRSA but at a higher density (1.5 * 10(4)cfu/mL) for the three mecA MRSA strains. All four media demonstrated excellent sensitivity for MRSA detection (>=99%), but reduced levels of specificity (85-73%) when challenged with a range of meticillin susceptible S. aureus (MSSA) isolates. High levels of false positives (~50%) were also obtained with all chromogenic media when tested with mec-negative borderline oxacillin-resistant S. aureus (BORSA) isolates. CONCLUSION: Although false positives may be obtained with some strains of MSSA and BORSA, the high sensitivity of these media and their ability to recover almost all MRSA tested (including oxacillin-susceptible and mecC-positive strains) confirm the value of chromogenic agar in MRSA detection. PMID- 26679723 TI - The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction. AB - To understand others' minds is crucial for survival; however, it is quite puzzling how access to others' minds can be--to some extent--direct and not necessarily mediated by conceptual reasoning. Recent advances in neuroscience have led to hypothesize a role for motor circuits not only in controlling the elementary physical features of movement (e.g., force, direction, and amplitude), but also in understanding and shaping human behavior. The concept of "motor cognition" refers to these aspects, and neurophysiological, neuroimaging, and behavioral studies in human and nonhuman primates support this view. From a clinical perspective, motor cognition represents a challenge in several domains. A thorough investigation of the neural mechanisms mediating motor action/intention understanding and automatized/compulsive behaviors seems to be a promising way to tackle a range of neurodevelopmental and drug-related disorders. On the one hand, anomalies in motor cognition may have cascade effects on social functioning in individuals with autism spectrum disorder (ASD); on the other, motor cognition may help explain the pathophysiology of drug-seeking and drug taking behaviors in the most severe phase of drug addiction (i.e., see drug dependence, motor low-order cue reactivity). This may represent a promising approach that could improve the efficacy of rehabilitative interventions. The only way to shed light on multifactorial disorders such as ASD and drug addiction is through the investigation of their multiple factors. This motor way can promote new theoretical and experimental perspectives that would help bridge the gap between the basic neuroscience approach and clinical practice. PMID- 26679726 TI - Decontamination of breast pump milk collection kits and related items at home and in hospital: guidance from a Joint Working Group of the Healthcare Infection Society and Infection Prevention Society. AB - INTRODUCTION: A variety of methods are in use for decontaminating breast pump milk collection kits and related items associated with infant feeding. This paper aims to provide best practice guidance for decontamination of this equipment at home and in hospital. It has been compiled by a Joint Working Group of the Healthcare Infection Society and the Infection Prevention Society. METHODS: The guidance has been informed by a search of the literature in Medline, the British Nursing Index, the Cumulative Index to Nursing and Allied Health Literature, Midwifery and Infant Care, and the results of two surveys of UK neonatal units in 2002/3 and 2006, and of members of the Infection Prevention Society in 2014. Since limited good quality evidence was available from these sources, much of the guidance represents good practice based on the consensus view of the Working Group. KEY RECOMMENDATIONS: CONCLUSION: This guidance provides practical recommendations to support the safe decontamination of breast pump milk collection kits for healthcare professionals to use and communicate to other groups such as parents and carers. PMID- 26679728 TI - How do you solve a problem like multidrug-resistant Gram-negative bacteria? PMID- 26679727 TI - Clostridium difficile infection incidence: impact of audit and feedback programme to improve room cleaning. AB - BACKGROUND: Audit and feedback programmes (AFPs) using fluorescent marking lead to improvements in room cleaning but have not been linked to reduced Clostridium difficile infection (CDI) incidence. AIM: To evaluate the impact of an AFP on hospital-acquired CDI incidence. METHODS: In 2012, a hospital-wide AFP was implemented. Fluorescent marking of high-touch surfaces was used to assess discharge cleaning thoroughness. Weekly audit results were presented to cleaning staff. Interrupted time-series analysis was used to test for changes in the trend and level of hospital-acquired CDI incidence between the pre-intervention (January 2008 to December 2011) and post-intervention (April 2012 to June 2015) periods. FINDINGS: In all, 1002 audits were performed and room cleaning thoroughness improved from 49% to 90%. Hospital-acquired CDI incidence fell from 54 to 42 cases per 100,000 patient-days following the intervention whereas non hospital-acquired CDI incidence rose from 43 to 52 cases per 100,000 patient days, although both exhibited a downward trend post intervention. Time-series analysis showed that hospital-acquired CDI incidence was declining at a rate of 0.59 cases per 100,000 patient-days per quarter before the intervention. Following programme implementation, the rate of decline accelerated by an additional 1.35 cases per 100,000 patient-days per quarter (P < 0.05). Hand hygiene compliance increased minimally post intervention. CONCLUSION: Implementation of an AFP using fluorescent marking resulted in improved thoroughness of room cleaning and appeared to result in an enhanced downward trend in CDI incidence, although part of this decline could be due to changes in local CDI epidemiology or improved hand hygiene. PMID- 26679729 TI - Health insurance database for post-discharge surveillance of surgical site infection following arthroplasty. AB - BACKGROUND: Surgical site infection surveillance (SSI) is important for the improvement of care and patient safety. Most SSI surveillance systems focus on hospital settings, whereas numerous infectious events occur after discharge. AIM: To evaluate the patient care trajectory after discharge, we linked the hospital discharge database and the National Health Insurance Cross-Schemes Information System (NHI-CIS) to trace hip or knee arthroplasty infection (HKAI). METHODS: A retrospective analysis was performed using the permanent 1/97th sample of the whole NHI-CIS database. A total of 1739 patients underwent hip or knee arthroplasty between January 1st, 2011 and December 31st, 2011. Patients rehospitalized for HKAI were detected using a specific published algorithm. Non rehospitalized HKAI patients were identified using a novel tracking algorithm based on ambulatory care consumption: nurse intervention, antibiotics and bandage purchase. FINDINGS: Of the 1739 studied patients, 20 patients (1.1%) were rehospitalized for HKAI. Fourteen (70%) of the HKAI events occurred within the first two months after surgery, two occurring during the patients' surgical hospital stay. Using ambulatory care data, 10 additional cases were suspected of developing HKAI in the year following their surgery. HKAI incidence rate was then estimated to be 1.76% (95% confidence interval: 1.14-2.38%). CONCLUSION: Although the study sample was limited, we demonstrated that each HKAI occurring after discharge could not be traced by the in-hospital information system alone. This result emphasizes the need for having a passive routine tool for post-discharge surveillance such as the NHI-CIS database. PMID- 26679730 TI - Effects of Female Dietary Restriction in a Rabbit Growth Line During Rearing on Reproductive Performance and Embryo Quality. AB - Maternal diet prior to mating has an effect on reproductive performance. We analysed the effect of maternal dietary restriction during rearing on reproductive performance, the embryo development and foetal growth. Females were categorized in two groups: (i) does with ad libitum access to feed or (ii) restricted. Two experiments were performed: (i) after 1 month, receptive females from both experimental groups were artificially inseminated and the reproductive performance was recorded during three reproductive cycles; at the first insemination, the body weight and perirenal fat thickness were recorded, and (ii) females from both experimental groups were inseminated, and 24 h later, embryos were recovered and transferred to recipient females from a maternal line. Later, embryonic implantation was assessed at day 14 by laparoscopy and foetal growth was monitored by ultrasound examination. In experiment 1, no differences in kindling rate was found, but prolificacy was showed to be higher in ad libitum does, which also were heavier than restricted ones. In experiment 2, no differences among does either in body weight, in perirenal fat thickness or in reproductive performance (ovulation rate and embryo recovery rate) were related to differences in feed intake. However, despite similar embryonic implantation losses, embryos from restricted females demonstrated higher foetal and gestational losses. Embryos from restricted does presented lower foetal growth than embryos from ad libitum does. Therefore, our results demonstrated that nutrition before first conception in a rabbit line selected for growth rate may impact on the embryo and results in a disturbance in gestational losses and foetal growth over all reproductive life. PMID- 26679731 TI - The complete mitochondrial genome of the white-browed laughingthrush Garrulax sannio (Passeriformes: Leiothrichidae). AB - The complete mitochondrial genome of the white-browed laughingthrush Garrulax sannio was assembled using next-generation sequencing (NGS) technology. The double-stranded circular genome is 17 848 bp in length, including 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), and 2 putative control region. All PCGs are initiated with the ATG codon except for COX1 with GTG as its start codon. Five distinct types of stop codons are present, i.e., AGA (ND5), AGG (COX1 and ND1), TAA (ATP6, ATP8, COX2, CYTB, and ND4L), TAG (ND6), and the incomplete codon T/TA (COX3, ND2, ND3, and ND4). The nucleotide composition is moderately asymmetric (28.94% A, 32.82% C, 15.00% G, and 23.24% T) with an overall GC content of 47.82% ("light strand"). Phylogenetic analysis indicated a close genetic relationship between this species and its congeners G. perspicillatus, G. cineraceus, and G. canorus. PMID- 26679732 TI - An Uncertain Future for Clinical Oncology Training in the UK. PMID- 26679733 TI - Colorectal Cancer. PMID- 26679734 TI - Cardiac Side-effects of Breast Radiotherapy. PMID- 26679735 TI - Perovskite-Type LaSrMnO Electrocatalyst with Uniform Porous Structure for an Efficient Li-O2 Battery Cathode. AB - Perovskite is an excellent candidate as low cost catalyst for Li-O2 cells. However, the limited porosity, which impedes molecular transport, and the inherent low electronic conductivity are the main barriers toward production of high-performance electrodes. Here, we designed a hierarchical porous flexible architecture by coating thin mesoporous yet crystalline LaSrMnO layers throughout a graphene foam to form graphene/meso-LaSrMnO sandwich-like nanosheets. In this well-designed system, the macropore between nanosheets facilitates O2 and Li(+) diffusion, the mesopore provides large surface area for electrolyte immersion and discharge products deposition, the perovskite phase catalyst decreases reactive overpotential, and the graphene serves as conductive network for electrons transport. When used as a freestanding electrode of Li-O2 cell, it shows high specific capacity, superior rate capability, and cyclic stability. Combination of mesoporous perovskites with conductive graphene networks represents an effective strategy for developing efficient electrodes in various energy storage systems. PMID- 26679736 TI - Goodness of fit tools for dose-response meta-analysis of binary outcomes. AB - Goodness of fit evaluation should be a natural step in assessing and reporting dose-response meta-analyses from aggregated data of binary outcomes. However, little attention has been given to this topic in the epidemiological literature, and goodness of fit is rarely, if ever, assessed in practice. We briefly review the two-stage and one-stage methods used to carry out dose-response meta analyses. We then illustrate and discuss three tools specifically aimed at testing, quantifying, and graphically evaluating the goodness of fit of dose response meta-analyses. These tools are the deviance, the coefficient of determination, and the decorrelated residuals-versus-exposure plot. Data from two published meta-analyses are used to show how these three tools can improve the practice of quantitative synthesis of aggregated dose-response data. In fact, evaluating the degree of agreement between model predictions and empirical data can help the identification of dose-response patterns, the investigation of sources of heterogeneity, and the assessment of whether the pooled dose-response relation adequately summarizes the published results. (c) 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. PMID- 26679737 TI - Ecophysiological and phytochemical response to ozone of wine grape cultivars of Vitis vinifera L. AB - Vitis vinifera sensitivity to tropospheric ozone (O3) has been evidenced in several studies. In this work, physiological and metabolic effects of O3 on two wine cultivars of V. vinifera (i.e. Maturano and San Giuseppe) have been studied. Moreover, chlorogenic acid (CGA) production, in consideration of its importance in the biosynthetic pathway of polyphenols and as antioxidant, has been investigated. Maturano cultivar resulted more sensitive to O3, as evidenced by the gas exchange reduction at the early stage of treatment, and by the increase in Ci/Ca and the decoupling of net photosynthesis and the stomatal conductance at the end of the treatment. Unexpectedly, O3 did not activate stilbene production. Ozone induced an early CGA decrease, significantly more consistent in cv. Maturano, and an increase after 8 days, more consistent in cv. S. Giuseppe. These results suggest that CGA could be considered a biochemical marker of O3-induced stress in V. vinifera. PMID- 26679738 TI - Working memory training improves emotion regulation ability: Evidence from HRV. AB - Emotion regulation during social situations plays a pivotal role in health and interpersonal functioning. In this study, we propose a working memory training approach to improve emotion regulation ability. This training promotes an updating function that is a crucial modulated process for emotion regulation. In the present study, the participants in the training group completed a running memory task over 20 days of training. Their working memory capability and high frequency heart rate variability (HF-HRV) data on pretest and posttest were assessed and analyzed. Compared with the control group, the training group's reaction time in the 2-back working memory task was reduced significantly. In addition, the HF-HRV in the emotion regulation condition was increased after the 20-day training, which indicates that the working memory training effect could transfer to emotion regulation. In other words, working memory training improved emotion regulation ability. PMID- 26679739 TI - Sleep problems predict cortisol reactivity to stress in urban adolescents. AB - This study examined the role of sleep problems and sleep duration on stress related HPA axis reactivity among urban, low income adolescents. A total of 84 adolescents (M age 13.36 years; 50% male; 95% African American) and their parents provided information on adolescents' sleep problems and sleep quantity. Adolescents completed a standardized social stress test in the laboratory (the Trier Social Stress Test; TSST). Saliva samples collected before and after the TSST yielded measures of cortisol pre-test, 15 min post-test, and 55 min post test, as well as overall cortisol secretion and its increase (AUCG and AUCI). More sleep problems and longer sleep duration predicted higher cortisol reactivity to the TSST, particularly among females. Self-reports of sleep were more consistently related to stress-related cortisol reactivity than parent reports. Sleep problems and longer sleep duration may place adolescents at risk for HPA axis hyper-reactivity to stress, contributing to academic, behavioral and health problems. PMID- 26679740 TI - Synthesis of chiral alpha-hydroxy acids via palladium-catalyzed C(sp(3))-H alkylation of lactic acid. AB - Herein we report a Pd-catalyzed alkylation of lactic acid with the assistance of 8-aminoquinoline auxiliary. A wide range of alkyl iodides bearing beta-hydrogen atoms are compatible with the reaction conditions, providing a practical and straightforward alternative to access chiral alpha-hydroxy acids (AHAs). The new reactions have been applied for the synthesis of isotope-labeled AHAs and a sugar containing complex AHA. PMID- 26679741 TI - Corrigendum: Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model. PMID- 26679742 TI - Back-up procedures following complicated gastric pull-up procedure for esophageal reconstruction: Salvage with intestinal flaps. AB - BACKGROUND: Gastric pull-up (GPU) is the most common procedure for restoring the continuity of the alimentary tract. Yet, complications because of anastomotic problems are reported to be as high as 25% after this procedure. Managing the neck with anastomotic leakage or stricture following failed GPU and/or radiotherapy is formidable. We report our method, basic algorithm and results with the complicated GPU procedure management with intestinal transfers . PATIENTS AND METHODS: Nineteen cases referred to our department with complicated esophageal reconstruction following GPU procedure were included in this report. Of the19 patients, 18 had undergone GPU procedure for reconstruction after cancer resection (mean age 55 years) and one for idiopathic esophagitis (mean age 45years). Fifteen patients presented with severe stricture formation and 4 patients with leakage from the anastomotic site. Average time between the GPU and salvage procedures was 7.3 months for patients with stricture formation and 15.5 days for patients with leakage. Pedicled colon interposition (n = 8) was used when the upper end of the gastric tube was located below the sternoclavicular junction. A free jejunal flap (n = 11) was utilized when defects were located at the neck (above the sternoclavicular junction). RESULTS: In all patients salvage procedures with intestinal flap transfer were successful with complete flap survival. Post-operative period was uneventful except of two patients with pedicled colon interposition who presented minor leakage post-operatively (10.5%). This was treated with conservative means, leading to spontaneous healing. The average follow-up for the patients with tumor resection was 11.8 months (range: 6 to 30) after the salvage procedure. All patients resumed smooth oral intake eventually. There were 16 patients who could feed with solid diet, whereas three patients were able to tolerate only soft diet. CONCLUSION: Intestinal tissues can be safely and successfully transferred as salvage procedures, with meticulous technique, careful patient selection and individual flap design. While gastric pull-up remains a good procedure for esophageal reconstruction, the methods described in this report are useful as back-up armaments in complicated cases. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:567-572, 2016. PMID- 26679743 TI - Axial allometry in a neutrally buoyant environment: effects of the terrestrial aquatic transition on vertebral scaling. AB - Ecological diversification into new environments presents new mechanical challenges for locomotion. An extreme example of this is the transition from a terrestrial to an aquatic lifestyle. Here, we examine the implications of life in a neutrally buoyant environment on adaptations of the axial skeleton to evolutionary increases in body size. On land, mammals must use their thoracolumbar vertebral column for body support against gravity and thus exhibit increasing stabilization of the trunk as body size increases. Conversely, in water, the role of the axial skeleton in body support is reduced, and, in aquatic mammals, the vertebral column functions primarily in locomotion. Therefore, we hypothesize that the allometric stabilization associated with increasing body size in terrestrial mammals will be minimized in secondarily aquatic mammals. We test this by comparing the scaling exponent (slope) of vertebral measures from 57 terrestrial species (23 felids, 34 bovids) to 23 semi-aquatic species (pinnipeds), using phylogenetically corrected regressions. Terrestrial taxa meet predictions of allometric stabilization, with posterior vertebral column (lumbar region) shortening, increased vertebral height compared to width, and shorter, more disc-shaped centra. In contrast, pinniped vertebral proportions (e.g. length, width, height) scale with isometry, and in some cases, centra even become more spool-shaped with increasing size, suggesting increased flexibility. Our results demonstrate that evolution of a secondarily aquatic lifestyle has modified the mechanical constraints associated with evolutionary increases in body size, relative to terrestrial taxa. PMID- 26679745 TI - A Novel, Sporicidal Formulation of Ethanol for Glove Decontamination to Prevent Clostridium difficile Hand Contamination During Glove Removal. AB - Decontamination of gloves before removal could reduce the risk for contamination of hands of personnel caring for patients with Clostridium difficile infection. We demonstrated that a novel sporicidal formulation of ethanol rapidly reduced C. difficile spores on gloved hands without adverse odor, respiratory irritation, or staining of clothing. PMID- 26679744 TI - A functional polymorphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection. AB - Enterovirus 71 (EV71), one of the major pathogens of Hand, foot and mouth disease (HFMD), results in millions of infections and hundreds of deaths each year in Southeast Asia. Biased infection and variable clinical manifestations of EV71 HFMD indicated that host genetic background played an important role in the occurrence and development of the disease. We identified the mRNA profiles of EV71 HFMD patients, which type I interferon (IFN) pathway related genes were down regulated. Four single nucleotide polymorphisms (SNPs) of type I IFN receptor 1 (IFNAR1) were chosen to analyze their relationships to EV71 infection. We found that genotype GG of promoter variant rs2843710 was associated with the susceptibility and severity to EV71 HFMD. In addition, we assessed the regulatory effects of rs2843710 to IFN stimulated genes (ISGs), and found that the expressions of IFNAR1, OAS1 and MX1 were significantly lower in patients with rs2843710 genotype GG. And rs2843710 allele G showed weaker transcriptional activity compared with allele C. Our study indicated that rs2843710 of IFNAR1 was associated with the susceptibility and severity of EV71 HFMD in Chinese Han populations, acting as a functional polymorphism by regulating ISGs expression, such as OAS1 and MX1. PMID- 26679746 TI - Shape-mediated margination and demargination in flowing multicomponent suspensions of deformable capsules. AB - We present detailed simulations and theory for flow-induced segregation in suspensions of deformable fluid-filled capsules with different shapes during simple shear flow in a planar slit. This system is an idealized model for transport for blood cells and/or drug carriers in the microcirculation or in microfluidic devices. For the simulations, an accelerated implementation of the boundary integral method was employed. We studied the binary mixtures of spherical and ellipsoidal capsules, varying the aspect ratio kappa of the ellipsoid while keeping constant either (a) equatorial radius or (b) volume. Effects of a variety of parameters was studied, including kappa, volume fraction and number fraction of the spherical capsules in the mixture. In suspensions where the ellipsoids have the same equatorial radius as the spheres, capsules with lower kappa marginate. In suspension where the ellipsoids have the same volume as the spheres, ellipsoidal (both oblate and prolate) capsules are seen to demarginate in a mixture of primarily spherical capsules. To understand these results, a mechanistic framework based on the competition between wall-induced migration and shear-induced collisions is presented. A simplified drift-diffusion theory based on this framework shows excellent qualitative agreement with simulation results. PMID- 26679747 TI - Monitor unit optimization in stereotactic body radiotherapy for small peripheral non-small cell lung cancer patients. AB - The increasingly attractive stereotactic body radiotherapy (SBRT) treatment for stage I lung cancer is concomitant with a large amount of monitor units (MU), leading to excessive out-of-field dose and prolonged beam-on time. The study aims to reduce the MU number and shorten the beam-on time by optimizing the planning parameters. Clinically acceptable treatment plans from fourteen patients suffered from peripheral stage I non-small cell lung cancer (NSCLC) were created in the study. Priority for the upper objective of the target (PUOT), strength and Max MU setting in the MU objective function (MUOF) were adjusted respectively to investigate their effect on MU number, organs at risk (OARs) sparing and beam-on time. We found that the planning parameters influenced the MU number in a PUOT, strength and Max MU dependent manner. Combined with high priority for the UOT (HPUOT) and MUOF, the MU number was reduced from 443 +/- 25 to 228 +/- 22 MU/Gy without compromising the target coverage and OARs sparing. We also found beam-on time was proportional to MU number and it could be shortened from 7.9 +/- 0.5 to 4.1 +/- 0.4 minutes. PMID- 26679749 TI - Degradation in carbon stocks near tropical forest edges. AB - Carbon stock estimates based on land cover type are critical for informing climate change assessment and landscape management, but field and theoretical evidence indicates that forest fragmentation reduces the amount of carbon stored at forest edges. Here, using remotely sensed pantropical biomass and land cover data sets, we estimate that biomass within the first 500 m of the forest edge is on average 25% lower than in forest interiors and that reductions of 10% extend to 1.5 km from the forest edge. These findings suggest that IPCC Tier 1 methods overestimate carbon stocks in tropical forests by nearly 10%. Proper accounting for degradation at forest edges will inform better landscape and forest management and policies, as well as the assessment of carbon stocks at landscape and national levels. PMID- 26679750 TI - Antimicrobial activity of hydroxytyrosol: a current controversy. AB - This study focus on the main factors that affect the antimicrobial capacity of hydroxytyrosol, including the concentration (200, 400, and 1000 MUg/mL), target strains, and the culture media (nutrient-rich and less-rich culture media). The potential HT degradation was also evaluated by HPLC-PAD. Kinetic parameters from growth curves showed that HT concentrations produced a doses-dependent shift when compared to the untreated control. In most of the cases, the highest tested dose (1000 MUg/mL) was needed to inhibit growth of the selected strains. However, all the strains were able to grow even at the highest HT dose when cultivated in nutrient-rich culture media. It was observed that HT concentrations were reduced by about 15%, except for Escherichia coli 533 and 679 in Muller Hinton broth, where HT was reduced up to 35%. The results showed a limited antimicrobial activity, contrary to information previously published in some research papers. PMID- 26679752 TI - Corrigendum. PMID- 26679753 TI - Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment. AB - Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively. Adequate central nervous system prophylaxis and mediastinal irradiation contributed to the therapeutic success; however, the role of radiation therapy is debated due to toxicity concerns and the excellent results obtained with radiation-free programs especially in pediatric patients. With these modern schedules, localized radiotherapy and/or hematopoietic stem cell transplants could be generally omitted, and considered only for high-risk patients identified through postinduction computed tomography/positron-emission tomography scans, minimal residual disease analysis, and new genetics and genomics. New clinical studies will have to confirm the value of these assays for risk-oriented therapy, while further therapeutic progress is expected from the introduction of new drugs and targeting agents. PMID- 26679754 TI - Management of giant intracranial aneurysms. PMID- 26679751 TI - Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice. AB - Wilson disease (WD) is a hepatoneurological disorder caused by mutations in the copper-transporter, ATP7B. Copper accumulation in the liver is a hallmark of WD. Current therapy is based on copper chelation, which decreases the manifestations of liver disease, but often worsens neurological symptoms. We demonstrate that in Atp7b(-/-) mice, an animal model of WD, liver function can be significantly improved without copper chelation. Analysis of transcriptional and metabolic changes in samples from WD patients and Atp7b(-/-) mice identified dysregulation of nuclear receptors (NRs), especially the liver X receptor (LXR)/retinoid X receptor heterodimer, as an important event in WD pathogenesis. Treating Atp7b(-/ ) mice with the LXR agonist, T0901317, ameliorated disease manifestations despite significant copper overload. Genetic markers of liver fibrosis and inflammatory cytokines were significantly decreased, lipid profiles normalized, and liver function and histology were improved. CONCLUSIONS: The results demonstrate the major role of an altered NR function in the pathogenesis of WD and suggest that modulation of NR activity should be explored as a supplementary approach to improving liver function in WD. (Hepatology 2016;63:1828-1841). PMID- 26679755 TI - Using intron splicing trick for preferential gene expression in transduced cells: an approach for suicide gene therapy. AB - Suicide gene therapy is one of the most innovative approaches in which a potential toxic gene is delivered to the targeted cancer cell by different target delivery methods. We constructed a transfer vector to express green fluorescent protein (GFP) in transduced cells but not in packaging cells. We placed gfp under the control of the cytomegalovirus (CMV) promoter, which is positioned between the two long-terminal repeats in reverse direction. The intron-2 sequence of the human beta globin gene with two poly-A signals and several stop codons on the antisense strand was placed on the leading strand between the CMV promoter and gfp. For lentiviral production, the HEK293T and line were co-transfected with the PMD2G, psPAX2 and pLentiGFP-Ins2 plasmids. The HEK293T and line were transduced with this virus. PCR was performed for evaluation of intron splicing in transduced cells. The GFP expression was seen in 65% of the cells transduced. The PCR amplification of the genomic DNA of transduced cells confirmed the splicing of intron 2. The strategy is significant to accomplish our goal for preserving the packaging cells from the toxic gene expression during viral assembly and the resultant reduction in viral titration. Also it serves to address several other issues in the gene therapy. PMID- 26679757 TI - Defect-engineered graphene chemical sensors with ultrahigh sensitivity. AB - We report defect-engineered graphene chemical sensors with ultrahigh sensitivity (e.g., 33% improvement in NO2 sensing and 614% improvement in NH3 sensing). A conventional reactive ion etching system was used to introduce the defects in a controlled manner. The sensitivity of graphene-based chemical sensors increased with increasing defect density until the vacancy-dominant region was reached. In addition, the mechanism of gas sensing was systematically investigated via experiments and density functional theory calculations, which indicated that the vacancy defect is a major contributing factor to the enhanced sensitivity. This study revealed that defect engineering in graphene has significant potential for fabricating ultra-sensitive graphene chemical sensors. PMID- 26679756 TI - Screening of potential biomarkers for cholangiocarcinoma by integrated analysis of microarray data sets. AB - Cholangiocarcinoma (CCA) continues to harbor a difficult prognosis and it is difficult to diagnose in its early stages. The molecular mechanisms of CCA oncogenesis and progression are poorly understood. This study aimed to identify candidate biomarkers for CCA. Integrated analysis of microarray data sets was performed to identify differentially expressed genes (DEGs) between CCA and normal tissues. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to identify the functions of DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed. The expressions of DEGs were validated in human CCA tissues by qRT-PCR. A set of 712 DEGs were identified in CCA compared with normal tissues, including 306 upregulated and 406 downregulated DEGs. It can be shown from the KEGG pathway analysis that some pathways may have important roles in pathology of CCA, including peroxisome proliferator-activated receptor signaling pathway, bile secretion, cell cycle, fat digestion and absorption. PPI network indicated that the significant hub proteins were PKM, SPP1 and TPM1. The abnormally overexpression PKM, SPP1 and TPM1 were closely related to oncogenesis and progression of CCA. PKM, SPP1, TPM1, COL1A1 and COL1A2 may serve as candidate biomarkers for diagnosis and prognosis of CCA. PMID- 26679758 TI - Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma Derived 3AB-OS Cancer Stem Cells. AB - Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 and p27 CDK inhibitors. Let-7d also decreased sarcosphere-and-colony forming ability, two features associated with self-renewing, and it reduced the expression of stemness genes, including Oct3/4, Sox2, Nanog, Lin28B, and HMGA2. Moreover, let-7d induced mesenchymal-to-epithelial-transition, as shown by both N-Cadherin-E-cadherin switch and decrease in vimentin. Surprisingly, such switch was accompanied by enhanced migratory/invasive capacities, with a strong increase in MMP9, CXCR4 and VersicanV1. Let-7d- overexpression also reduced cell sensitivity to apoptosis induced by both serum-starvation and various chemotherapy drugs, concomitant with decrease in caspase-3 and increase in BCL2 expression. Our data suggest that let 7d in 3AB-OS-CSCs could induce plastic-transitions from CSCs-to-non-CSCs and vice versa. To our knowledge this is the first study to comprehensively examine the expression and functions of let-7d in OS-CSCs. By showing that let-7d has both tumor suppressor and oncogenic functions in this context, our findings suggest that, before prospecting new therapeutic strategies based on let-7d modulation, it is urgent to better define its multiple functions. J. Cell. Physiol. 231: 1832 1841, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26679759 TI - Automated parameter estimation for biological models using Bayesian statistical model checking. AB - BACKGROUND: Probabilistic models have gained widespread acceptance in the systems biology community as a useful way to represent complex biological systems. Such models are developed using existing knowledge of the structure and dynamics of the system, experimental observations, and inferences drawn from statistical analysis of empirical data. A key bottleneck in building such models is that some system variables cannot be measured experimentally. These variables are incorporated into the model as numerical parameters. Determining values of these parameters that justify existing experiments and provide reliable predictions when model simulations are performed is a key research problem. RESULTS: Using an agent-based model of the dynamics of acute inflammation, we demonstrate a novel parameter estimation algorithm by discovering the amount and schedule of doses of bacterial lipopolysaccharide that guarantee a set of observed clinical outcomes with high probability. We synthesized values of twenty-eight unknown parameters such that the parameterized model instantiated with these parameter values satisfies four specifications describing the dynamic behavior of the model. CONCLUSIONS: We have developed a new algorithmic technique for discovering parameters in complex stochastic models of biological systems given behavioral specifications written in a formal mathematical logic. Our algorithm uses Bayesian model checking, sequential hypothesis testing, and stochastic optimization to automatically synthesize parameters of probabilistic biological models. PMID- 26679760 TI - Triiodothyronine accelerates and enhances the antipsychotic effect of risperidone in acute schizophrenia. AB - In acute psychotic schizophrenia patients we investigated if the combination of triiodothyronine (T3) plus risperidone was more effective when compared to risperidone monotherapy. Thirty-two in-patients meeting the DSM-IV-TR diagnostic criteria for schizophrenia and without thyroid disease received risperidone (flexibly adjusted dose for tolerability) and were randomized to additionally receive either T3 (25 MUg daily; risperidone plus T3 group) or placebo (risperidone plus placebo group). Treatment lasted until meeting the response to treatment criteria defined as score of <= 3 on the Clinical Global Impression Severity and Improvement scales. Acute psychotic episode symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) at treatment initiation and at the final study assessment. Fourteen patients were randomized to receive risperidone plus T3 and eighteen to receive risperidone plus placebo. The time until treatment response was shorter in the risperidone plus T3 group relative to the risperidone plus placebo group (25.5 +/- 4.4 days vs 32.2 +/- 8.2 days, respectively; p = 0.001). Moreover, there was a greater reduction of BPRS-total score (p = 0.01) in the risperidone plus T3 group relative to the risperidone plus placebo group. Treatment with T3 was associated with shorter time to treatment response (beta = -0.440, p = 0.022) and with greater improvement in BPRS score (beta = 0.240, p = 0.053), independent of patients' gender, age, baseline BPRS score and mean risperidone dose. The study confirms that addition of T3 to risperidone was associated with accelerated and enhanced treatment response in acutely psychotic schizophrenic patients. PMID- 26679761 TI - Racial and ethnic trends and correlates of non-medical use of prescription opioids among adolescents in the United States 2004-2013. AB - PURPOSE: Our objective was to elucidate the trends in non-medical use of prescription opioids (NMUPO) among whites, African-Americans, and Hispanic adolescents in the United States. An additional aim was to examine the sociodemographic, behavioral, and psychosocial correlates of NMUPO across each of these aforementioned racial and ethnic groups. METHODS: Data was derived from the National Survey on Drug Use and Health (NSDUH) involving non-Hispanic white, African American, and Hispanic respondents ages 12-17 (n = 164,028) and spanning the years 2004-2013. Consistent with prior NSDUH-based studies, respondents reporting use within the previous 12 months were classified as nonmedical prescription opioid users. Logistic regression was used to examine significance of trend year and correlates of NMUPO. RESULTS: Non-Hispanic white youth consistently reported higher levels of NMUPO as did older adolescents (ages 15 17) and females. However, there was a decrease in the prevalence of NMUPO overall driven largely by a significant decline (p < 0.001) in NMUPO among non-Hispanic whites of approximately 35% over the study period such that by 2013 no statistically significant differences across race/ethnicity remained. Further, logistic regression models found that externalizing behaviors such as comorbid drug use and fighting was associated with NMUPO and religiosity and parental involvement were identified as protective correlates. CONCLUSIONS: To our knowledge, this is the first study to identify a declining trend in NMUPO among adolescents. Although the present study findings provide a source for optimism, there is still a relatively high prevalence of NMUPO and it remains to be seen whether our findings portend a long-term decline. Given the harm done by NMUPO, continued awareness and targeted prevention efforts should be implemented. PMID- 26679762 TI - Low levels of posttraumatic stress symptoms and psychiatric symptomatology among third-generation Holocaust survivors whose fathers were war veterans. AB - There is an ongoing debate regarding the intergenerational transmission of Holocaust trauma to the third generation (TGH). However, due to the rareness of this population, there are no studies that have examined TGH individuals whose fathers were also victims of war-related trauma and captivity. This prospective study aimed to assess the role of parents' Holocaust background, fathers' posttraumatic stress symptoms (PTSS), and adult offspring's anxiety sensitivity (AS) in adult offspring's PTSS and psychiatric symptomatology. A sample of 123 Israeli father-child dyads (42 TGH and 71 non-TGH), that included 80 former prisoners of war (ex-POWs) dyads and a comparison group of 44 veteran dyads, completed AS, PTSS and psychiatric symptomatology self-report measures. Fathers were assessed 17 years following the Yom Kippur War (T1: 2008) while offspring took part in T2 (2013-2014). Surprisingly, results show that TGH participants reported lower levels of PTSS and psychiatric symptomatology than non-TGH participants, regardless of their fathers' captivity status. Interestingly, a moderated mediation analysis indicated that offspring's AS mediated the association between Holocaust background and participants' PTSS and psychiatric symptomatology, only among ex-POWs' offspring. This study provides evidence for relatively lower levels of PTSS and psychiatric symptomatology among TGH individuals whose fathers were war veterans. Ex-POWs' adult offspring who are grandchildren of Holocaust survivors reported lower levels of AS that was related to lower levels of PTSS and psychiatric symptomatology. PMID- 26679763 TI - A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. AB - Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16-35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first episode schizophrenia patients. PMID- 26679764 TI - Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia. AB - Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion. PMID- 26679765 TI - Amelanotic acral lentiginous melanoma mimicking diabetic ulcer: a challenge to diagnose and treat. PMID- 26679766 TI - A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding. AB - BACKGROUND: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets. METHODS: We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from variable regions, where all variants bind HLA. These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets. RESULTS: We applied this method to predict CD8+ T-cell targets in influenza A H7N9 hemagglutinin and significantly increased the number of potential vaccine targets compared to the number of targets discovered using the traditional approach where low-frequency peptides are excluded. CONCLUSIONS: We developed a webserver with an intuitive visualization scheme for summarizing the T cell-based antigenic potential of any given protein or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/. PMID- 26679769 TI - Sensitized Two-NIR-Photon Z->E Isomerization of a Visible-Light-Addressable Bistable Azobenzene Derivative. AB - Two-NIR-photon-triggered Z->E isomerization of an azobenzene was accomplished by covalently linking a two-photon-harvesting triarylamine antenna to a thermally stable ortho-fluorinated azobenzene derivative. The obtained photoswitch is fully addressable with visible and NIR light by using one-photon and two-photon excitation, respectively, with the latter offering enhanced penetration depth and improved spatial resolution. PMID- 26679767 TI - Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. AB - Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current day pharmaceutical agents, most notably in the area of cancer therapy. Examples include Taxol, vinblastine, and camptothecin. These structurally unique agents function by novel mechanisms of action; isolation from natural sources is the only plausible method that could have led to their discovery. In addition to terrestrial plants as sources for starting materials, the marine environment (e.g., ecteinascidin 743, halichondrin B, and dolastatins), microbes (e.g., bleomycin, doxorubicin, and staurosporin), and slime molds (e.g., epothilone B) have yielded remarkable cancer chemotherapeutic agents. Irrespective of these advances, cancer remains a leading cause of death worldwide. Undoubtedly, the prevention of human cancer is highly preferable to treatment. Cancer chemoprevention, the use of vaccines or pharmaceutical agents to inhibit, retard, or reverse the process of carcinogenesis, is another important approach for easing this formidable public health burden. Similar to cancer chemotherapeutic agents, natural products play an important role in this field. There are many examples, including dietary phytochemicals such as sulforaphane and phenethyl isothiocyanate (cruciferous vegetables) and resveratrol (grapes and grape products). Overall, natural product research is a powerful approach for discovering biologically active compounds with unique structures and mechanisms of action. Given the unfathomable diversity of nature, it is reasonable to suggest that chemical leads can be generated that are capable of interacting with most or possibly all therapeutic targets. PMID- 26679768 TI - Informal Health Provider and Practical Approach to Lung Health interventions to improve the detection of chronic airways disease and tuberculosis at primary care level in Malawi: study protocol for a randomised controlled trial. AB - BACKGROUND: In developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at primary health care level are weak and patients turn to unskilled informal health providers to seek health care. Delayed diagnosis and treatment of these diseases facilitates increased severity and tuberculosis transmission. The World Health Organisation developed the Practical Approach to Lung Health strategy which has been shown to improve the management of both tuberculosis and chronic airways disease. The guidelines address the need for integrated guidelines for tuberculosis and chronic airways disease. Engaging with informal health providers has been shown to be effective in improving health services uptake. However, it is not known whether engaging community informal health providers would have a positive impact in the implementation of the Practical Approach to Lung Health strategy. We will use a cluster randomised controlled trial to determine the effect of using the two interventions to improve case detection and treatment of patients with tuberculosis and chronic airways disease. METHODS: A three-arm cluster randomised trial design will be used. A primary health centre catchment population will form a cluster, which will be randomly allocated to one of the arms. The first arm personnel will receive the Practical Approach to Lung Health strategy intervention. In addition to this strategy, the second arm personnel will receive training of informal health providers. The third arm is the control. The effect of interventions will be evaluated by community surveys. Data regarding the diagnosis and management of chronic cough will be gathered from primary health centres. DISCUSSION: This trial seeks to determine the effect of Informal Health Provider and Practical Approach to Lung Health interventions on the detection and management of chronic airways disease and tuberculosis at primary care level in Malawi. TRIAL REGISTRATION: The unique identification number for the registry is PACTR201411000910192--21 November 2014. PMID- 26679770 TI - Familial Atrial Septal Defect and Sudden Cardiac Death: Identification of a Novel NKX2-5 Mutation and a Review of the Literature. AB - OBJECTIVE: Atrial septal defect (ASD) is the second most common congenital heart defect (CHD) and is observed in families as an autosomal dominant trait as well as in nonfamilial CHD. Mutations in the NKX2-5 gene, located on chromosome 5, are associated with ASD, often combined with conduction disturbances, cardiomyopathies, complex CHD, and sudden cardiac death as well. Here, we show that NKX2-5 mutations primarily occur in ASD patients with conduction disturbances and heritable ASD. Furthermore, these families are at increased risk of sudden cardiac death. RESULTS: We screened 39 probands with familial CHD for mutations in NKX2-5 and discovered a novel mutation in one family (2.5%) with ASD and atrioventricular block. A review of the literature revealed 59 different NKX2 5 mutations in 202 patients. Mutations were significantly more common in familial cases compared to nonfamilial cases (P = 7.1 * 10(-9) ). The majority of patients (74%) had ASD with conduction disturbance. Nineteen patients (15%) of 120 with familial ASD and conduction disturbance died from sudden cardiac death of which nine (8%) were confirmed mutation carriers, and 10 were possible carriers. CONCLUSIONS: NKX2-5 mutations mainly occur in familial CHD, the signature phenotype is ASD with conduction disturbances and mutation carriers are at increased risk of sudden cardiac death. We suggest that familial ASD patients should be screened for NKX2-5 mutations and, if they are mutation carriers, implantation of an implantable cardioverter-defibrillator should be considered in these patients. PMID- 26679772 TI - Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated alpha-Substituted Acrylate Esters. AB - The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated alpha-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Bronsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the alpha substituent of the alpha,beta-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %. PMID- 26679771 TI - Microchimerism and regulation in living related kidney transplant families. AB - Long-term harmful effects of immunosuppressive drugs and chronic rejection are a persistent impetus to establish methods to induce immunological tolerance to allografts. PCR-based studies have found evidence that humans and other placental mammals can have prolonged extremely low levels of maternal cells as well as other non-self cells, referred to as microchimerism. The persistence of these cells suggests a mechanism for the maintenance of the regulatory T-cell (Treg) responses frequently detected in offspring to non-inherited maternal antigens. We test the hypothesis that the detection of very low copy levels of insertion/deletion (Indel) alleles consistent with non-inherited maternal genes, will correlate with immune regulation to non-inherited maternal antigens as detected by a trans-vivo Delayed-Type Hypersensitivity (tvDTH) assay in kidney transplant recipients, normal donors and their immediate biological family members. Preliminary data reported here compares qPCR amplification of rare DNA templates in the peripheral blood polymorphonuclear (PMN) fraction of cells, with the results of tvDTH assays for linked suppression of recall antigen responses in the presence of non-inherited maternal antigens [NIMA]. The two assays do not show a definitive correlation. PMID- 26679773 TI - 'We needed to change the mission statement of the marriage': biographical disruptions, appraisals and revisions among couples living with endometriosis. AB - The concept of biographical disruption has been widely applied in sociological explorations of chronic illness and has been subject to much theoretical scrutiny, reflection and development. However, little attention has been given to the impact of biographical disruption beyond the individual level. This article explores the concept from a dyadic perspective, utilising data from an exploratory, qualitative study (ENDOPART) that investigated the impact of endometriosis on women and their male partners. In total, 22 couples participated in in-depth, semi-structured, face-to-face interviews. The women and their partners were interviewed separately and, in most cases, simultaneously, by different interviewers. Data analysis was informed by an interpretivist relational approach, foregrounding the meanings participants applied to their experiences, treating interviews as accounts, and exploring partners' accounts in relation to one another. Two analytic approaches generated several themes for exploration in the context of the concept of biographical disruption: sex and intimacy; planning for and having children; working lives and social lives. The article argues that biographical disruptions are social and inter-relational processes and discusses how couples living with endometriosis negotiated these disruptions, how they were appraised and how lives and expectations were revised as a result. PMID- 26679774 TI - Brachyspira pilosicoli-induced avian intestinal spirochaetosis. AB - Avian intestinal spirochaetosis (AIS) is a common disease occurring in poultry that can be caused by Brachyspira pilosicoli, a Gram-negative bacterium of the order Spirochaetes. During AIS, this opportunistic pathogen colonises the lower gastrointestinal (GI) tract of poultry (principally, the ileum, caeca, and colon), which can cause symptoms such as diarrhoea, reduced growth rate, and reduced egg production and quality. Due to the large increase of bacterial resistance to antibiotic treatment, the European Union banned in 2006 the prophylactic use of antibiotics as growth promoters in livestock. Consequently, the number of outbreaks of AIS has dramatically increased in the UK resulting in significant economic losses. This review summarises the current knowledge about AIS infection caused by B. pilosicoli and discusses various treatments and prevention strategies to control AIS. PMID- 26679775 TI - Host microbiota modulates development of social preference in mice. AB - BACKGROUND: Mounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour. OBJECTIVE: In this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming). METHODS AND RESULTS: Using the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR-based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I , IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice. CONCLUSION: These results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice. PMID- 26679777 TI - Olfaction following endoscopic skull base surgery. AB - PURPOSE OF REVIEW: As endoscopic skull base surgery advances and becomes more common, recognizing and understanding all possible risks and complications of these procedures is a significant responsibility of the operating surgeon. Olfaction is a deficit often ignored or trivialized by the treating physician, in spite of its loss causing major impacts on our patients' quality of life. RECENT FINDINGS: Olfactory dysfunction after endoscopic skull base surgery is still being debated in the literature, with evidence supporting both sides. With some studies denying any loss, others suggesting temporary deficits, and still others showing long-term damage, standardization of testing and high levels of awareness of this possible complication should be the prevailing practice. SUMMARY: Future goals of any endoscopic skull base surgeon should be to use objective olfactory testing before and after surgery, collect information on rates of dysfunction in their patients, and offer treatment options as necessary while tracking the efficacy of those options in this patient population. PMID- 26679778 TI - Innovations in nasal valve surgery. AB - PURPOSE OF REVIEW: This article reviews current practices in nasal valve repair and highlights recent innovations in the medical literature. RECENT FINDINGS: A surgeon's choice regarding a proper nasal valve repair technique depends heavily on the patient's site of obstruction. While classical maneuvers to improve the internal and external nasal valves have been employed for several decades, increasing understanding of lateral wall insufficiency and its role in nasal valve compromise has led to improvement of proposed methods for correcting the nasal valve. Radiofrequency-induced thermotherapy, the upper lateral strut graft, stairstep graft, and nasal valve lift techniques are described in detail. These four techniques offer innovative means of dealing with the challenge of nasal valve collapse resulting in nasal obstruction. SUMMARY: This review article provides an overview of the current practice in the field of nasal valve repair and summarizes recent technical advances in the field. PMID- 26679776 TI - Properly defining the targets of a transcription factor significantly improves the computational identification of cooperative transcription factor pairs in yeast. AB - BACKGROUND: Transcriptional regulation of gene expression in eukaryotes is usually accomplished by cooperative transcription factors (TFs). Computational identification of cooperative TF pairs has become a hot research topic and many algorithms have been proposed in the literature. A typical algorithm for predicting cooperative TF pairs has two steps. (Step 1) Define the targets of each TF under study. (Step 2) Design a measure for calculating the cooperativity of a TF pair based on the targets of these two TFs. While different algorithms have distinct sophisticated cooperativity measures, the targets of a TF are usually defined using ChIP-chip data. However, there is an inherent weakness in using ChIP-chip data to define the targets of a TF. ChIP-chip analysis can only identify the binding targets of a TF but it cannot distinguish the true regulatory from the binding but non-regulatory targets of a TF. RESULTS: This work is the first study which aims to investigate whether the performance of computational identification of cooperative TF pairs could be improved by using a more biologically relevant way to define the targets of a TF. For this purpose, we propose four simple algorithms, all of which consist of two steps. (Step 1) Define the targets of a TF using (i) ChIP-chip data in the first algorithm, (ii) TF binding data in the second algorithm, (iii) TF perturbation data in the third algorithm, and (iv) the intersection of TF binding and TF perturbation data in the fourth algorithm. Compared with the first three algorithms, the fourth algorithm uses a more biologically relevant way to define the targets of a TF. (Step 2) Measure the cooperativity of a TF pair by the statistical significance of the overlap of the targets of these two TFs using the hypergeometric test. By adopting four existing performance indices, we show that the fourth proposed algorithm (PA4) significantly out performs the other three proposed algorithms. This suggests that the computational identification of cooperative TF pairs is indeed improved when using a more biologically relevant way to define the targets of a TF. Strikingly, the prediction results of our simple PA4 are more biologically meaningful than those of the 12 existing sophisticated algorithms in the literature, all of which used ChIP-chip data to define the targets of a TF. This suggests that properly defining the targets of a TF may be more important than designing sophisticated cooperativity measures. In addition, our PA4 has the power to predict several experimentally validated cooperative TF pairs, which have not been successfully predicted by any existing algorithms in the literature. CONCLUSIONS: This study shows that the performance of computational identification of cooperative TF pairs could be improved by using a more biologically relevant way to define the targets of a TF. The main contribution of this study is not to propose another new algorithm but to provide a new thinking for the research of computational identification of cooperative TF pairs. Researchers should put more effort on properly defining the targets of a TF (i.e. Step 1) rather than totally focus on designing sophisticated cooperativity measures (i.e. Step 2). The lists of TF target genes, the Matlab codes and the prediction results of the four proposed algorithms could be downloaded from our companion website http://cosbi3.ee.ncku.edu.tw/TFI/. PMID- 26679779 TI - New innovations in office-based rhinology. AB - PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) affects millions of patients worldwide, with significant health and financial implications. There is an immense utilization of resources involved, including prescription medications and surgical interventions. With increased emphasis on sound resource allocation and patient convenience, recent years have witnessed significant expansion in office based rhinologic procedures. The purpose of this review is to discuss new technologic innovations designed to facilitate treatment of sinonasal disease in the clinic setting. RECENT FINDINGS: Vacuum-powered polypectomy, in-office navigation, photodynamic therapy, and drug-eluting sinus implants will be specifically addressed. The clinical indications, advantages and disadvantages, as well as accompanying evidence will be elucidated. Thus far, preliminary clinical studies have demonstrated the safety, feasibility, and efficacy of vacuum-powered polypectomy and steroid-eluting implants in select CRS patients with recurrent nasal polyposis. In-vitro studies have also illustrated the antimicrobial and anti-inflammatory effects of photodynamic therapy, but clinical trials evaluating its role in CRS are still ongoing. SUMMARY: The review discusses novel tools recently developed to expand our in-office armamentarium of rhinologic procedures in management of sinonasal disease. Ultimately, it is at the discretion of individual surgeons to determine how such innovations can be integrated into their clinical practice. SDC VIDEO LINK: http://links.lww.com/COOH/A18. PMID- 26679780 TI - Indications for open procedures in the endoscopic era. AB - PURPOSE OF REVIEW: Endoscopic sinus surgery became the gold standard in inflammatory disorders of the nose and paranasal sinuses, in cerebrospinal fluid leak and epistaxis management, and established its efficacy in the oncology of the region. However, there are certain limitations which make an external approach mandatory. This article reviews the recent literature describing the cases where an open procedure is still indicated. RECENT FINDINGS: Despite the evolution of endoscopic surgery external approaches are still indicated. Osteoplastic flap remains an option for the refractory inflammation of the frontal sinus. Benign and malignant tumours with lateral or superior extension, neurovascular involvement, and bony/soft tissue erosion usually require an external approach. Superior and lateral posterior wall defects of frontal sinus with cerebrospinal fluid leak may mandate an open procedure. Management of severe epistaxis may still necessitate in selected cases an external approach when endoscopic surgery fails and embolization setting is not available. SUMMARY: Although advances in endoscopic instrumentation and techniques steadily decrease the indications for external approaches, they continue to have a role in the management of nasal disorders. This study summarizes the recent literature and provides a comprehensive review of the up-to-date remaining indications for open procedures in the nose and paranasal sinuses. PMID- 26679781 TI - Surgical repair of nasal septal perforations: an update. AB - PURPOSE OF REVIEW: Nasal septal perforations can have a substantial impact on patient's nasal breathing and subsequent quality of life. Various surgical techniques have previously been described for the repair of these perforations. In this review, we examine the most recent literature evaluating surgical techniques for the repair of nasal septal perforations. RECENT FINDINGS: Twenty seven studies evaluating 646 patients were included. None of these studies compared different surgical techniques. Four major categories of surgical techniques are described: multilayer, single layer, patch, and resection. Within these broad categories there is much heterogeneity in both the individual surgical technique and material used for reconstruction. However, the overall closure rate in all studies evaluated was 88%. SUMMARY: The diversity in surgical techniques demonstrated in this review would indicate that surgeons are not satisfied with the current surgical approaches for the repair of nasal septal perforations. However, the overall closure rates presented in this review are very favorable. Future comparative studies are needed to better evaluate these techniques. PMID- 26679782 TI - Rhinology: updates on best practice. PMID- 26679783 TI - Laryngeal cancer in nondrinker nonsmoker young patients: a distinct pathological entity? AB - PURPOSE OF REVIEW: Laryngeal cancer published literature was reviewed, with emphasis on reporting on young patients (<40 years). With such information, to comment on the evidence or not, that such patients, should they be nondrinkers and nonsmokers, have a differing cause and genetic/molecular profile rather than a spectrum of the classic disease. RECENT FINDINGS: Head and neck cancer in young patients is documented at a rate of 0.4-3.6%, with laryngeal cancer being identified in less than 2% of all diagnosed head and neck cancer patients overall. Head and neck cancer in nondrinking nonsmokers has been reported from tertiary clinical hospitals only, with few patients having a diagnosis of laryngeal cancer, and thus their documented drinking and smoking habits may be considered suspect. Most of the molecular or genetic studies on young patients, who probably have had varying degrees of drinking and smoking habits, have been reported on nonlaryngeal head and neck sites. These finding should be confirmed on a 'pure group' of young patients (<40 years) with laryngeal cancer who confirm that they have been nondrinkers, and nonsmokers. SUMMARY: Many authors comment that laryngeal cancer in young (<40 years) nondrinking nonsmoking patients is likely explained by some molecular or genetic level abnormality rather than histological and should be considered a distinct group. However, because of a low incidence of such patients and the rapid development in genetic sequencing, that such a project be completed requires greater collaboration between clinicians and pathologists. PMID- 26679784 TI - Periodization and physical therapy: Bridging the gap between training and rehabilitation. AB - BACKGROUND: Exercise prescription and training progression for competitive athletes has evolved considerably in recent decades, as strength and conditioning coaches increasingly use periodization models to inform the development and implementation of training programs for their athletes. Similarly, exercise prescription and progression is a fundamental skill for sport physical therapists, and is necessary for balancing the physiological stresses of injury with an athlete's capacity for recovery. OBJECTIVE: This article will provide the sport physical therapist with an overview of periodization models and their application to rehabilitation. SUMMARY: In recent decades models for exercise prescription and progression also have evolved in theory and scope, contributing to improved rehabilitation for countless athletes, when compared to care offered to athletes of previous generations. Nonetheless, despite such advances, such models typically fail to fully bridge the gap between such rehabilitation schemes and the corresponding training models that coaches use to help athletes peak for competition. Greater knowledge of periodization models can help sport physical therapists in their evaluation, clinical reasoning skills, exercise progression, and goal setting for the sustained return of athletes to high level competition. PMID- 26679786 TI - Synchronous telecommunications in medical education. PMID- 26679787 TI - Monitoring cerebral ischemia using cerebral oximetry: pros and cons. PMID- 26679785 TI - Apolipoprotein A-V gene therapy for disease prevention / treatment: a critical analysis. AB - Apolipoprotein (apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol (TG) homeostasis. Whereas a portion of hepatic derived apoA-V is secreted into plasma and functions to facilitate lipoprotein lipase-mediated TG hydrolysis, another portion is recovered intracellularly, in association with cytosolic lipid droplets. Loss of apoA-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease. Single nucleotide polymorphisms (SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions. Likewise, rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction. Genetically engineered mouse models and human population studies suggest that, in certain instances, supplementation with wild type (WT) apoA-V may have therapeutic benefit. It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance. On the other hand, subjects with hypertriglyceridemia of independent origin (unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner. Improvement in the ability to identify individuals predicted to benefit, advances in gene transfer technology and the strong connection between HTG and heart disease, point to apoA V supplementation as a viable disease prevention / therapeutic strategy. Candidates would include individuals that manifest chronic TG elevation, have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels. PMID- 26679789 TI - Proposal of Gleason-like grading system of canine prostate carcinoma in veterinary pathology practice. AB - Gleason grading - the most useful predictor of prognosis for prostate cancer in men - was updated at a 2005 consensus conference by the International Society of Urological Pathology. Since Gleason-like growth patterns have been recognised in dogs, this study aimed to apply the modified Gleason grading to 45 canine prostate carcinomas. A single primary growth pattern was observed in 28 cases, a secondary pattern in 11 cases and a tertiary pattern in 6 cases. Cribriform, solid and small acinar/ductal were the most common primary, secondary and tertiary morphological patterns, respectively. The highest Gleason score (GS10) was obtained in 46.7% of cases. Nine of 14 metastasizing cases were classified as GS10. Gleason pattern 5 was present in 33 of cases. This study suggests that the modified Gleason grading, based on specific histological growth patterns existing in canine prostate carcinomas, may be accepted as a grading system for histopathology in the practice settings in order to complete the clinical assessment for the best management of the patient. PMID- 26679788 TI - Egg yolk IgY antibodies: A therapeutic intervention against group A rotavirus in calves. AB - Bovine group A rotavirus (RVA) is considered the major cause of diarrhea in intensively reared neonatal calves. Chicken egg yolk antibodies (IgY) are efficient in protecting neonatal calves from RVA diarrhea; however, the value of this intervention in calves once diarrhea has appeared is unclear. The aim of the present study was to evaluate the application of RVA-specific IgY as a passive treatment in those cases. The experimental groups were: G1=RVA-specific IgY treatment; G2=no Ab treatment; and G3=colostrum deprived+no Ab treatment. IgY treatment significantly reduced virus shedding, diarrhea duration and severity compared to G2 and G3 calves. However, it caused a partial suppression of systemic Ab responses to RVA that could be associated with less severe diarrhea. The oral treatment with IgY for 7days was associated with significantly higher antibody secreting cell responses in the calves compared with other groups of animals. PMID- 26679790 TI - Short communication: Experimental toxocarosis in Chinese Kun Ming mice: Dose dependent larval distribution and modulation of immune responses. AB - Toxocarosis is an important parasitic zoonosis which is mainly caused by the infective larvae of Toxocara canis. To identify whether there are correlations among the infectious dose, the larval migrans and immune modulation in inbred Chinese Kun Ming (KM) mice, experimental infections were carried out with a range of dosages of 100, 500, 1000, 2000, and 3000 embryonated eggs (EE). Pathogenic reactions were observed in terms of physical and central nervous symptoms. Distributions of T. canis larvae in liver, lung, kidney, heart and brain organs were respectively detected by scanning tissue sections. Moreover, quantitative real-time PCR was employed to identify the variations of Th2 immune response. The results showed that high inocula resulted in advanced larval emergences and arrested migrations in liver, lung, kidney and brain. However, no larvae were found in any of the histological sections of heart tissues. Higher levels of interleukin (IL)-4, IL-5, and IL-10 were detected along with the increasing inoculation doses, but the heaviest inoculum (3000 EE in this study) resulted in the sharp reduction of these ILs. Although no neurological symptoms or mortalities were noticed, these results indicated dose-dependent distribution patterns and immune regulations of T. canis larvae infection in KM mice. PMID- 26679791 TI - Sedative effect of 2-phenoxyethanol and essential oil of Lippia alba on stress response in gilthead sea bream (Sparus aurata). AB - The anesthetic efficacy of the essential oil of Lippia alba (EOLA) in Sparus aurata was evaluated by induction and recovery times of anesthesia. After, specimens were exposed to anesthetics low concentrations for 4h, under nonstress or stress conditions. Range 100-300 MUL L(-1) EOLA induced anesthesia. Plasmatic cortisol, glucose, lactate, and osmolality enhanced after EOLA exposure in the undisturbed (UF) and stressed fish (SF). Lower corticotropin-releasing hormone binding-protein expression occurred in SF/EOLA compared with 2-PHE/stress combination or to EOLA/undisturbed conditions. Stress processes reduced prolactin (PRL) expression in the control fish, while UF exhibited reduced PRL levels after exposure to both anesthetics. Proopiomelanocortin (POMCa) mRNA was higher after 2 PHE exposure in SF compared to control; POMCb expression was higher in SF/EOLA in contrast to control and UF/EOLA conditions. Thus, EOLA was an effective anesthetic, but it was unable to prevent a stress response in S. aurata; while 2 PHE is advisable to sedate S. aurata without causing stress, but it was not effective at preventing a stress response in the present work. PMID- 26679792 TI - (+)-Catechin inhibition of transmissible gastroenteritis coronavirus in swine testicular cells is involved its antioxidation. AB - Transmissible gastroenteritis virus (TGEV) causes transmissible gastroenteritis (TGE), especially in newborn piglets, which severely threatens the worldwide pig industry. In this study, (+)-catechin was evaluated for its antiviral effect against TGEV in vitro. Viability assays revealed that (+)-catechin treatment exerted a dose-dependent rescue effect in TGEV-infected ST cells, and this result was only obtained with the post-treatment application of (+)-catechin. The viral yields in (+)-catechin-treated cultures were reduced by almost three log10 units. Quantitative real-time PCR analysis of the TGEV genome revealed that TGEV RNA replication was restricted after (+)-catechin treatment. Intracellular reactive oxygen species (ROS) detection showed that (+)-catechin alleviated ROS conditions induced by TGEV infection. Our results showed that (+)-catechin exerts an inhibitory effect on TGEV proliferation in vitro and is involved its antioxidation. PMID- 26679793 TI - Effects of environmental carcinogen benzo(a)pyrene on canine adipose-derived mesenchymal stem cells. AB - Dogs and their owners share the same environment and are subjected to similar environmental risk factors for developing breast cancer. Adipose tissue-derived mesenchymal stem cells (ADMSCs) may affect development and progression of breast cancer. In this study, we evaluated the effects of environmental carcinogen benzo(a)pyrene (BaP) on proliferation and differentiation of ADMSCs isolated from dogs. We characterized eight canine ADMSC lines and studied the effects of BaP on cell proliferation and differentiation. BaP did not inhibit cell proliferation of ADMSCs; however, BaP significantly inhibited differentiation potential of ADMSCs into adipocytes. BaP down-regulated AhR protein levels; however, increased its translocation from the cytoplasm to nucleus and suppressed PPARgamma expression during adipogenesis. BaP increased the expression of AhR signaling pathway protein, cytochrome P450 (CYP1A1) in ADMSCs. Our data suggest that canine ADMSCs are susceptible to the environmental carcinogen BaP through AhR and PPARgamma signaling pathways and may contribute to canine mammary carcinogenesis. PMID- 26679794 TI - Bovine tuberculosis in domestic pigs: Genotyping and distribution of isolates in Argentina. AB - Bovine tuberculosis is caused by Mycobacterium bovis and affects primarily cattle, among many other mammal species. In this study, 250 isolates of M. bovis collected from pigs slaughtered in Argentina were typed by spoligotyping. Over half of the isolates (66%) grouped into two spoligotypes. Moreover, SB0140 was the most frequent spoligotype detected in the three performed samplings. In addition, 195 isolates were typed through variable number of tandem repeats (VNTR) by selecting 7 loci (MIRU 16-26- 31 and ETR A-B-C-D). The relationship among the patterns was performed using a goeBURST algorithm and the main clonal complexes grouped 110 isolates (56%). Although pigs shared genotypes with cattle (n = 21), some patterns were detected only in pigs (n=14). These findings suggest the pig as a source ofM. bovis infection to cattle. PMID- 26679795 TI - Evaluation of the in vitro activity of flumequine against field isolates of Brachyspira hyodysenteriae. AB - Flumequine is a quinolone derivative used in veterinary medicine to treat enteric infections, mainly those caused by Gram negative bacteria and also some Gram positive. Some recent reports by field practitioners have suggested that its use in swine dysentery outbreaks can minimize the impact of this disease. This study aims to evaluate the in vitro anti-Brachyspira hyodysenteriae activity of flumequine. Forty eight field isolates of the bacterium were evaluated using a microdilution test. The lack of colon bioavailability studies of flumequine in pigs makes it difficult to establish the true efficacy of this antibiotic for swine dysentery control. Nonetheless, the relatively high values of MIC50 (50 MUg/mL) and MBC50 (50 MUg/mL) obtained suggest poor activity against B. hyodysenteriae. Flumequine activity in swine dysentery outbreaks could be related to its activity against other bacteria, different from B. hyodysenteriae, engaged in swine dysentery pathogenesis. PMID- 26679796 TI - Pattern characterization of genes involved in non-specific immune response in Staphylococcus aureus isolates from intramammary infections. AB - Staphylococcus aureus isolated from mammary gland are characterized by different genetic patterns. Ninety four isolates from 33 dairy herds were analyzed by the means of a microarray to investigate S. aureus virulence patterns and the distribution of genes believed to be involved in immune evasion. None of the 94 isolates considered were MRSA. However, 50% of the isolates belonged to complexes related to MRSA and to human diseases, while only about 25% of them can be considered as exclusively of bovine origin. The distribution of clonal complexes and the different gene patterns observed confirmed the presence of an influence of geographical localization. The assessment of the influence of genes related to immune evasion on quarter milk cell count showed as four of them showed to be significantly associated to an increase quarter milk SCC. These genes could be potential target for developing new vaccines against S. aureus. PMID- 26679797 TI - Feline mesenchymal stem cells and supernatant inhibit reactive oxygen species production in cultured feline neutrophils. AB - Feline bone marrow-derived MSCs (BMMSCs), adipose-derived MSCs (AMSCs) and fibroblasts (FBs) were isolated and cultured. Tri-lineage differentiation assays and flow cytometry were used to characterize MSCs. Neutrophils (NPs) were isolated from whole blood and the NPs production of reactive oxygen reactive oxygen species (ROS) was measured. NPs were cultured alone, with MSC culture supernatant (SN), BMMSCs or AMSCs. NPs incubated with BMMSCs had significantly lower ROS production than NPs incubated with AMSCs (p=0.0006) or FB (p<0.0001); NPs ROS production significantly decreased with increasing BMMSC cell number (p=0.0023) and significantly increased with NPs were incubated with FB compared to BMMSC (p=0.0003). Both BMMSC SN and AMSC SN had statistically significantly lower ROS production than FB SN when incubated with NPs (both p<0.0001). ROS production was significantly reduced with increased fractions of SN from BMMSCs (p=0.0467) and AMSCs (p=0.0017). PMID- 26679798 TI - Preliminary evidence of age-dependent clinical signs associated with porcine circovirus 2b in experimentally infected CH3/Rockefeller mice. AB - Mice and rats are susceptible to porcine circovirus 2b (PCV2) infection under field and experimental conditions. However, whether PCV2 induces disease in rodents remains a matter of debate. The objectives of the present study were to determine whether PCV2-induced disease in mice is age-dependent and whether intranasally inoculated animals are able to infect animals they come into contact with. Twenty-five CH3/Rockefeller mice were divided into six groups and intranasally inoculated with 25MUL of either PCV2b or PBS on days 0, 3 and 6. One group remained untreated. Two age groups were tested: 3-week-old mice and 6-week old mice. The administration of three PCV2 intranasal inoculations at intervals of three days was able to induce infection and support virus transmission in susceptible mice, regardless of the age at inoculation. The clinical signs associated with PCV2 infection were more severe in younger mice, and PCV2-DNA load was higher in their faeces. In conclusion, PCV2 induced disease in mice. PMID- 26679799 TI - Evaluation of the immunogenicity and diagnostic interference caused by M. tuberculosis SO2 vaccination against tuberculosis in goats. AB - The immunogenicity and diagnostic interference caused by M. tuberculosis SO2, a prototype vaccine first time tested in goats was evaluated. Tuberculosis-free goats were distributed in four groups: [1], non-vaccinated; [2], subcutaneously (SC) BCG vaccinated; [3], intranasally (IN) SO2 vaccinated and [4], SC SO2 vaccinated. Intradermal tuberculin and IFN-gamma tests using PPDs and alternative antigenic cocktails containing mainly ESAT-6 and CFP-10 (E/C) were applied at different times post-vaccination. Results showed a significant (p<0.05) increase in the number of reactors detected using both PPD-based intradermal and IFN-gamma tests at different times in all the vaccinated groups. No intradermal reactivity was detected in the vaccinated goats using a cocktail containing E/C, Rv3615c and Rv3020c. A higher overall reactivity was observed in the group [4] in comparison with the other vaccinated groups. Results showed that antigens used to differentiate BCG vaccinated animals could be potentially used to differentiate SO2 vaccinated ones. PMID- 26679800 TI - Influence of hands-on experience on pig farmers' attitude towards alternatives for surgical castration of male piglets. AB - This study evaluates the influence of practical experience with alternatives for surgical castration (SC) on farmer attitudes. Nineteen farmers in Flanders were surveyed before (ex-ante) and after (ex-post) performing each of five treatments on farm: 1) SC with analgesia (SCAN); 2) SC with CO2 anaesthesia (SCCO2); 3) immunocastration (IM); 4) production of entire males (EM); and 5) SC without pain relief (SCN). For SCCO2 and SCAN, farmers mainly experienced disadvantages in terms of increased labour, costs and complexity. Hands-on experience promoted EMas a valid alternative for SCN due to the actual and perceived improvement in performance and profitability as well as the reduced labour demands. Experience with IM did not fully fulfil the favourable ex-ante expectations resulting in a level of dissatisfaction and a less favourable general attitude ex-post. PMID- 26679801 TI - Drinking water application of Denagard(r) Tiamulin for control of Brachyspira pilosicoli infection of laying poultry. AB - Avian intestinal spirochaetosis (AIS) caused by Brachyspira spp., and notably Brachyspira pilosicoli, is common in layer flocks and reportedly of increasing incidence in broilers and broiler breeders. Disease manifests as diarrhoea, increased feed consumption, reduced growth rates and occasional mortality in broilers and these signs are shown in layers also associated with a delayed onset of lay, reduced egg weights, faecal staining of eggshells and non-productive ovaries. Treatment with Denagard(r) Tiamulin has been used to protect against B. pilosicoli colonisation, persistence and clinical presentation of AIS in commercial layers, but to date there has been no definitive study validating efficacy. Here, we used a poultry model of B. pilosicoli infection of layers to compare the impact of three doses of Denagard(r) Tiamulin. Four groups of thirty 17 week old commercial pre-lay birds were all challenged with B. pilosicoli strain B2904 with three oral doses two days apart. All birds were colonised within 2 days after the final oral challenge and mild onset of clinical signs were observed thereafter. A fifth group that was unchallenged and untreated was also included for comparison as healthy birds. Five days after the final oral Brachypira challenge three groups were given Denagard(r) Tiamulin in drinking water made up following the manufacturer's recommendations with doses verified as 58.7 ppm, 113 ppm and 225 ppm. Weight gain body condition and the level of diarrhoea of birds infected with B. pilosicoli were improved and shedding of the organism reduced significantly (p=0.001) following treatment with Denagard(r) Tiamulin irrespective of dose given. The level and duration of colonisation of organs of birds infected with B. pilosicoli was also reduced. Confirming previous findings we showed that the ileum, caeca, colon, and both liver and spleen were colonised and here we demonstrated that treatment with Denagard(r) Tiamulin resulted in significant reduction in the numbers of Brachyspira found in each of these sites and dramatic reduction in faecal shedding (p<0.001) to approaching zero as assessed by culture of cloacal swabs. Although the number of eggs produced per bird and the level of eggshell staining appeared unaffected, egg weights of treated birds were greater than those of untreated birds for a period of approximately two weeks following treatment. These data conclusively demonstrate the effectiveness of Denagard(r) Tiamulin in reducing B. pilosicoli infection in laying hens. PMID- 26679802 TI - Immunoregulatory signal FoxP3, cytokine gene expression and IFN-gamma cell responsiveness upon porcine reproductive and respiratory syndrome virus (PRRSV) natural infection. AB - The study aims at evaluating gene expression of pro-inflammatory (IL-1beta, IL-8, TNF-alpha), pro-immune (IFN-gamma), anti-inflammatory (IL-10) cytokines and of the immunoregulatory signal FoxP3 in association with PRRSV-specific IFN-gamma secreting cell (SC) responsiveness upon PRRSV natural infection. Forty PRRSV negative pigs were assigned to two groups: 20 pigs were vaccinated at 3 weeks of age (weaning) against PRRSV (V-PRRSV) with a modified live virus vaccine (MLV) and 20 pigs were kept non-vaccinated (NV) as controls. Blood samples were collected at 3 (vaccination), 6, 8, 10, 12, 14, and 16 weeks of age. Natural infection occurred from 8 weeks of age onward in both groups and viremia lasted 8 weeks. In the early phase of infection, pro-inflammatory cytokines (IL-1beta, IL 8, TNF-alpha) showed a delayed increase concomitant with the peak of viremia in both groups. In both groups, IL-10 peaked at 12 weeks in association with the increase of pro-inflammatory cytokines. Conversely, in vaccinated pigs (V-PRRSV), IFN-gamma showed higher gene expression during the early phase of infection and a more intense secreting cell (SC) response in the late phase. Differently, gene expression of the transcription factor FoxP3, expressed by T regulatory lymphocytes (Tregs), increased significantly in controls only and was associated with the rise of the viral load. Moreover, FoxP3 levels remained significantly higher during the late phase of infection and paralleled with lower levels of IFN gamma SC detected by ELISPOT. The expression/production of immunoregulatory signals involved in Treg activation could be a promising marker to study the immunobiology of PRRSV infection. PMID- 26679803 TI - Isolation and experimental inoculation of an S INDEL strain of porcine epidemic diarrhea virus in Japan. AB - In 2013, porcine epidemic diarrhea (PED) was reported in Japan for the first time in 7years and caused significant economic losses. In the present study, we isolated PED virus (PEDV) circulating in Japan using Vero cell cultures and analyzed sequences of S1 genes of these PEDV isolates. Sequence analysis revealed that one of these strains contained distinct insertion and deletions in the S gene (i.e., S INDEL). Furthermore, inoculation of PEDV into 1-week-old pigs demonstrated that the S INDEL strain had a lower pathogenicity than the North American (NA) prototype strain. This is the first report comparing pathogenicity of an S INDEL strain with the NA prototype strain following experimental inoculation. Excretion of PEDV in the feces of S INDEL strain-inoculated pigs occurred later than in NA prototype strain-inoculated pigs. Thus, our findings suggested that the S INDEL strain had different viral dynamics than the NA prototype strain. PMID- 26679804 TI - Polymorphisms in the promoter region of the bovine lactoferrin gene influence milk somatic cell score and milk production traits in Chinese Holstein cows. AB - Lactoferrin is an iron-binding protein found in cow's milk that plays an important role in preventing mastitis caused by intramammary infection. In this study, 20 Chinese Holstein cows were selected randomly for PCR amplification and sequencing of the bovine lactoferrin gene promoter region and used for SNP discovery in the region between nucleotide positions -461 to -132. Three SNPs ( 270T>C, -190G>A and -156A>G) were identified in bovine lactoferrin, then Chinese Holstein cows (n=866) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA) based on the previous SNP information in this study, and the associations between SNPs or haplotype and milk somatic cell score (SCS) and production traits were analyzed by the least squares method in the GLM procedure of SAS. SNPs -270T>C and -156A>G showed close linkage disequilibrium (r(2)=0.76). The SNP -190G>A showed a significant association with SCS, and individuals with genotype GG had higher SCS than genotypes AG and AA. Associations were found between the SNPs -270T>C and -190G>A with SCS and the milk composition. The software MatInspector revealed that these SNPs were located within several potential transcription factor binding sites, including NF-kappaB p50, KLF7 and SP1, and may alter gene expression, but further investigation will be required to elucidate the biological and practical relevance of these SNPs. PMID- 26679805 TI - Co-localization of PTEN and E-cadherin in canine mammary hyperplasias and benign and malignant mammary tumors. AB - Fifty-four canine mammary lesions (15 hyperplasias, 7 adenomas and 32 carcinomas) were submitted to immunohistochemical analysis for the evaluation of PTEN and E cadherin co-expression. Subjects bearing mammary carcinomas were also submitted to a 2-year follow-up study to compare immunohistochemical results with overall survival. All the hyperplastic samples stained positive for both markers, 100% of adenomas were positive for PTEN and 86% for E-cadherin, and 69% and 34% of carcinomas were positive for PTEN and E-cadherin, respectively. Statistical analysis showed a positive correlation between these two proteins both considering all (p b 0.01) or malignant tumors (p < 0.05). The female dogs bearing tumors positively-stained for both markers had a longer overall survival (p < 0.05) and absence of lymphatics invasion (p < 0.05). Simultaneous double immunofluorescence confirmed the co-localization of the two proteins in neoplastic cells. Results reported in this study confirm the tumor suppressor effect of these two molecules. PMID- 26679806 TI - Feline hepatic biotransformation of diazepam: Differences between cats and dogs. AB - In contrast to humans and dogs, diazepam has been reported to induce severe hepatic side effects in cats, particularly after repeated dosing. With the aim to elucidate the mechanisms underlying this apparent sensitivity of cats to drug induced liver injury, in a series of in vitro experiments, the feline-specific biotransformation of diazepam was studied with liver microsomes obtained from cats and dogs and the possible inhibition of the bile salt export pump (Bsep) was measured in isolated membrane vesicles overexpressing feline and canine Bsep. In line with previous in vivo studies, the phase I metabolites nordiazepam, temazepam and oxazepam were measurable in microsomal incubations, although enzyme velocity of demethylases and hydroxylases differed significantly between cats and dogs. In cats, the main metabolite was temazepam, which also could be glucuronidated. In contrast to dogs, no other glucuronidated metabolites could be observed. In addition, in the membrane vesicles an inhibition of the transport of the Bsep substrate taurocholic acid could be observed in the presence of diazepam and its metabolites. It was concluded that both mechanisms, the slow biotransformation of diazepam as well the inhibition of the bile acid efflux that results in an accumulation of bile acids in the hepatocytes, seem to contribute to the liver injury observed in cats following repetitive treatment with diazepam. PMID- 26679807 TI - Nutrition, rumen health and inflammation in the transition period and their role on overall health and fertility in dairy cows. AB - Transition is a stressful period and critical for the entire cow's productive lifespan and reproduction. Optimal feeding management during transition period enables smooth metabolic adaptation to the initiation of lactation. Major nutritional challenge during this period is the urgent need to counteract the drastic deficits in energy and nutrients of the early-lactating cow. This is primarily done by inclusion of large amounts of concentrates in the diet during early lactation, causing major dietary imbalances with utmost importance for rumen health. Proper feeding management targeting rumen health in the transition period improves nutrient degradation and the net supply with energy and key nutrients of the host while preventing systemic disturbances and inflammation, events which are instrumental for cow's overall health and reproductive performance. The review provides insights into the role of, and gives practical hints regarding diet balancing efforts and feeding management strategies targeting rumen health and systemic inflammation during the periparturient period with the aim to enhance cow health and fertility. PMID- 26679808 TI - The bioavailability of medetomidine in eight sheep following oesophageal administration. AB - There is sound evidence that medetomidine is an effective analgesic for acute pain in sheep. In this study, 15 MUg kg(-1) of medetomidine was administered intravenously, and into the oesophagus, in a cross-over study, using eight sheep. Following intravenous administration, medetomidine could be detected in the plasma of these sheep for 120-180 min but following oesophageal administration, medetomidine could not be detected in the plasma of any sheep at any of 17 time points over four days. It is suspected that this is due to high first pass metabolism in the liver. Consequently, we conclude that future studies investigating the use of analgesics in orally-administered osmotic pumps in sheep should consider higher doses of medetomidine (e.g. >100 MUg kg(-1)), further investigations into the barriers of medetomidine bioavailability from the sheep gut, liver-bypass drug delivery systems, or other alpha2-adrenergic agonists (e.g. clonidine or xylazine). PMID- 26679809 TI - Promoter mutation and reduced expression of BRCA1 in canine mammary tumors. AB - Breast cancer 1, early onset (BRCA1) is one of the most important genes in human familial breast cancer, which also plays an important role in canine mammary tumors. The objectives of this study were to determine the promoter sequence of canine BRCA1, to investigate its promoter mutation status and to describe BRCA1 expression pattern in canine mammary tumors. The promoter sequence of canine BRCA1 was acquired by aligning human BRCA1 promoter sequence with canine genomic sequence and confirmed by standard promoter activity analysis. Same as human BRCA1 promoter, the CAAT box and G/C box were found in canine BRCA1 promoter. In order to explore the mutation status of the promoter region and to investigate the expression pattern of this gene, 10 normal canine mammary tissues, 15 benign mammary tumors and 15 malignant mammary tumors were used. By sequencing, 46.7% of the malignant mammary tumors were found with a deletion of one cytosine in the promoter region. The mRNA expression of BRCA1 was significantly reduced in benign and malignant mammary tumors (P<0.05), and the protein expression of BRCA1 was significantly reduced in malignant mammary tumors (P<0.05). This study is the first time to determine the canine BRCA1 promoter sequence and to describe the promoter mutation status in canine mammary tumors. PMID- 26679810 TI - Effect of colostrum and milk on small intestine expression of AQP4 and AQP5 in newborn buffalo calves. AB - Functional studies indicate differences in newborn gastrointestinal morphology and physiology after a meal. Both water and solutes transfer across the intestinal epithelial membrane appear to occur via aquaporins (AQPs). Given that the physiological roles of AQP4 and AQP5 in the developing intestine have not been fully established, the objective of this investigation was to determine their distribution, expression and respective mRNA in the small intestine of colostrums-suckling buffalo calves by using immunohistochemistry, Western blot, and reverse transcriptase-PCR analysis. Results showed different tissue distribution between AQP4 and AQP5 with the presence of the former along the enteric neurons and the latter in the endocrine cells. Moreover, their expression levels were high in the ileum of colostrum-suckling buffalo calves. The data present a link between feeding, intestinal development and water homeostasis, suggesting the involvement of these channel proteins in intestinal permeability and fluid secretion/absorption during this stage of development after birth. PMID- 26679811 TI - A multimodality imaging approach for guiding a modified endovascular coil embolization of a single intrahepatic portosystemic shunt in dogs. AB - Intrahepatic portosystemic shunts (IHPSS) in dogs are aberrant vascular anomalies that connect the portal and the systemic venous vessels. In most of the patients, the surgical approach is unfavourable due to the difficulties in isolating the IHPSS, making the option of a percutaneous transvenous coil embolization (PTCE) one of the safer occlusive procedures. This study describes the treatment of eight dogs with a single IHPSS using a multimodality imaging approach to guide the modified PTCE procedure. This new technique results in a decrease of 71% of the time of the entire procedure with the reduction of 91% in the time required involved the IHPSS identification and in the fluoroscopy exposure time avoiding the need for iodinated contrast agents during the procedure. Moreover, the placement of the catheter before the caval stent ensures its greater stability, enhancing the procedural safety in the phase when the coils are released and avoiding the risk of their dislocation. PMID- 26679812 TI - Quantitative analysis of ultrasonographic images and cytology in relation to histopathology of canine and feline liver: An ex-vivo study. AB - The aims of the present study were to investigate, in a standardized experimental condition, the usefulness of histogram analysis on ex-vivo ultrasonographic images of the liver of dogs and cats compared with histological alterations and to evaluate whether the combination of histogram parameters and cytology might improve diagnostic accuracy referring to optical microscopy as gold standard. Histogram-based parameters were calculated on ultrasonographic images of liver tissue samples collected from the cadavers of 68 dogs and 31 cats. Standard deviation of the histogram (SDH) had a higher sensitivity and specificity in the detection of the lesions in cat compared with dog. Matched results of cytology and SDH improved sensitivity and specificity in dog where as no substantial improvement was evident in cat. Quantitative analysis of ultrasonographic images of the liver in dog and cat could become a potentially useful tool in the distinction between normal and pathological organs. PMID- 26679813 TI - Lactobacillus and Lactobacillus cell-free culture supernatants modulate chicken macrophage activities. AB - Lactobacilli are commensal microbes that reside in the intestines of several species, including chickens. Structural constituents of lactobacilli are able to stimulate the host immune system. Macrophages are crucial players in both innate and adaptive immune systems. Here, we investigated the effects of Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus salivarius and their cell-free culture supernatants on the pro-inflammatory gene expression profile, nitric oxide (NO) production and phagocytosis by chicken macrophages. Substantial differences were found among Lactobacillus strains in their capacity to induce pro-inflammatory cytokines. L. acidophilus only up-regulated interferon (IFN) gamma, while L. reuteri and L. salivarius up-regulated interleukin (IL)-1beta, IL 6, IL-8 and IL-12 expression. Supernatant of L. salivarius up-regulated IL-1beta, IL-8 and IFN-gamma expression, while the other cell-free supernatants did not induce significant changes. Moreover, L. reuteri and L. salivarius increased macrophage phagocytosis, but all cell-free supernatants increased macrophage NO production and did not change phagocytosis activity. PMID- 26679814 TI - Protein mutations following adaptation of avian influenza viruses in different biological systems. AB - Traditionally, embryonated chicken eggs (ECE) are considered the gold standard for Influenza virus isolation and vaccine production. Nowadays, different biological systems have been improved and performed, in order to evaluate a feasible alternative to ECE. In fact, in a previous study, mammalian and avian cell cultures were successfully used for avian influenza viruses primary isolation from target tissues and virus propagation. This research is focused on the investigation of adaptive mutations that occur after influenza A virus amplification in ECE and cell cultures. The results of the study shows that avian influenza viruses after multiple passages in different biological systems undergo mutations, in particular, the largest number of amino acid substitutions occurred in all biological substrates in the hemagglutinin. PMID- 26679815 TI - Genetic diversity of porcine circovirus type 2 and implications for detection and control. AB - Porcine circovirus type 2 (PCV2) is the etiological agent of post- weaning multi systemic wasting syndrome (PMWS), an economically important disease of swine. Severe wasting and lymphadenopathy are typical signs of PMWS. Effective vaccines against PCV2 and reliable diagnostic tests are available. Since PCV2's discovery in the mid-90s and the introduction of commercial vaccines, several new recombinant strains and variants with genetic mutations have emerged. Two noteworthy changes include; a major type switching event that resulted in the previously predominant PCV2a genotype being replaced by PCV2b, and the recent emergence of a mutant PCV2b with a capsid protein containing an additional lysine. The mutant PCV2b exhibits increased virulence and is spreading rapidly in various regions of the world. This article provides an overview of the recent molecular epidemiology in the context of the current methods for the detection and prevention of PCV2, emphasizing the need for updated PCV2 vaccines. PMID- 26679816 TI - Mammaglobin as a diagnostic serum marker of complex canine mammary carcinomas. AB - Mammaglobin is a glycoprotein exhibiting homology to uteroglobin gene family. Although the biological function of the protein is not yet known it has been reported to act as marker for breast cancer in women. This study reports the expression of mammaglobin gene in canine mammary tumor condition. The gene was cloned, sequenced and heterologously expressed in Escherichia coli host system as 12 kDa (approx.) recombinant fusion protein. The expressed protein was further purified to homogeneity and confirmed by western blotting. Hyperimmune sera were raised against the expressed protein in rabbits and mice to standardize sandwich ELISA for relative quantification of circulating protein in the sera of dogs with mammary tumors. Based on receiver-operating characteristics analysis, the test was found to be 90% sensitive and 95% specific for a cut-off value of 0.177 with respect to histopathological staining in diagnosing canine mammary tumors and the protein level was not elevated in other diseased conditions. These findings indicate that it can act as a novel molecular marker for detecting mammary tumors in canines. PMID- 26679817 TI - Concurrent vaccination of pigs with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) protects against type 1 PRRSV but not against type 2 PRRSV on dually challenged pigs. AB - The objective of the present study was to evaluate the effect of concurrent vaccination of pigs with both type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against heterologous dual challenge of both genotypes and compare with single vaccination of pigs against heterologous single challenge of both genotypes. Pigs were administered both type 1 and type 2 PRRSV vaccine concurrently into separate anatomical sites at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Neutralizing antibodies (NA) were not detected in any pigs in any group (NA titer <2 log2) throughout the experiment. In addition, concurrent vaccination of pigs with two PRRSV genotypes had significantly lower numbers of type 1 and type 2 PRRSV specific interferon-gamma secreting cells (IFN-gamma-SC) compared to vaccination of pigs with type 1 or type 2 PRRSV only. Despite the decreased induction of type 1 PRRSV-specific IFN-gamma-SC, concurrent vaccination is still able to reduce type 1 PRRSV viremia whereas the decreased induction of type 2 PRRSV-specific IFN gamma-SC by concurrent vaccination correlates with lack of reduction of type 2 PRRSV viremia after dual challenge. The results of this study demonstrated that concurrent vaccination of pigs with two PRRSV genotypes is able to reduce the levels of type 1 PRRSV viremia and lung lesions but not able to reduce the levels of type 2 PRRSV viremia and lung lesions. PMID- 26679818 TI - Short communication: Genetic variants of Sarcocystis cruzi in infected Malaysian cattle based on 18S rDNA. AB - Sarcocystis species are pathogenic parasites that infect a wide range of animals, including cattle. A high prevalence of cattle sarcocystosis has been reported worldwide, but its status is unknown in Malaysia. This study focused on utilizing 18S rDNA to identify Sarcocystis species in Malaysian cattle and to determine their genetic variants. In this study, only Sarcocystis cruzi was detected in Malaysian cattle. The intra-species S. cruzi phylogenetic tree analysis and principal coordinate analysis (PCoA), respectively displayed two minor groups among the parasite isolates. This finding was supported by high Wright FST value (FST=0.647). The definitive hosts (dogs) may play a fundamental role in the development of S. cruzi genetic variants. Additionally, the existence of microheterogeneity within the S. cruzi merozoites and/or distinct genetic variants arisen from independent merozoites in mature sarcocysts, possibly contributed to the existence of intra-species variations within the population. PMID- 26679819 TI - The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes. AB - Many studies identified new components of the renin-angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1-7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1-7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1-7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1-7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1-7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17beta-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos. PMID- 26679820 TI - Thermal manipulation during broiler chicken embryogenesis: Effect on mRNA expressions of Hsp108, Hsp70, Hsp47 and Hsf-3 during subsequent post-hatch thermal challenge. AB - Effects of thermal manipulation during broiler chicken embryonic days 12-18 on body temperature (T(b)) and mRNA expressions of Hsp108, Hsp70, Hsp47 and Hsf-3 in muscle, heart and brain tissues during subsequent thermal challenge (TC) were investigated. Fertile chicken eggs were divided randomly into four groups (n=375): eggs in the control group were maintained at 37.8 degrees C and 56% (RH). Eggs in TM1 group were subjected to TM at 39 degrees C for 9h during ED 12 18. Eggs in the TM2 and TM3 groups were subjected to the same protocol of TM1 except for increasing the period of exposure to 12h and 18h, respectively. During TC (43 degrees C for 6h) at days 10 and 28, T(b) of TM chicks was significantly lower compared to controls. Furthermore, significant changes in mRNA expressions of Hsp108, Hsp70 and Hsp47 in muscle, heart and brain tissues were observed. PMID- 26679821 TI - Study of the immunomodulatory properties of gamithromycin and dexamethasone in a lipopolysaccharide inflammation model in calves. AB - The aim of this study was to define the in vivo immunomodulatory properties of the macrolide antibiotic gamithromycin in calves, with respect to the acute phase response. Additionally, the corticosteroid dexamethasone was included as a positive control immunomodulatory drug. Both drugs, as well as their combination,were studied in a previously developed inflammation model,which was initiated by an intravenous lipopolysaccharide (LPS) challenge (0.5 MUg/kg body weight). Twenty-four 4-week-old male Holstein Friesian calves were randomized into four groups: no pharmacological treatment (n = 6) or a pharmacological treatment with gamithromycin (n= 6), dexamethasone (n= 6) or their combination (n= 6) 1 h prior to LPS administration. Blood collection and clinical scoring were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of selected cytokines (tumour necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6)) and acute phase proteins (serum amyloid A and haptoglobin) were subsequently determined. Gamithromycin did not have any beneficial effect on the LPS-induced clinical signs (dyspnea, fever, anorexia and depression), nor on the studied inflammatory mediators. In the dexamethasone and combination groups, the occurrence of dyspnea and fever was not prominently influenced, although the calves recovered significantly faster from the challenge. Moreover, dexamethasone significantly inhibited the levels of TNF alpha and IL-6, suggesting a key role for these cytokines in sickness behaviour. In conclusion, unlike dexamethasone, gamithromycin did not directly reduce cytokine release in an LPS inflammation model in calves. PMID- 26679822 TI - Canine bone marrow cytological examination, classification and reference values: A retrospective study of 295 cases. AB - Cytologic assessment of bone marrow with knowledge of the hemogram represents an effective method to investigate hemic tissue and its function. To determine the spectrum and prevalence of canine bone marrow disorders over a 2 year period in a diagnostic laboratory setting achieved through a standard approach to cytologic bone marrow assessment. A retrospective study of bone marrow fine needle aspirates sample preparations, blood smears, hemogram data and case records. Of the 295 bone marrow samples evaluated, 90 (30.5%) were nondiagnostic samples. Of the remaining samples, 25.1% were classified as hyperplasia of which most were granulocytic hyperplasia (58.1% of the total hyperplasia), 19.3% had no cytological abnormalities, 12.9% had malignant hemopathy and 7.8% had hypo aplastic conditions. Only a small proportion of cases involved dysplasia (1.7%) and metastatic disease was detected in only one case (0.3%). Reference values of nucleated cells and the M/E ratio were calculated for normal and erythroid and granulocytic hyperplastic bone marrow. This study provides the spectrum and the prevalence of canine bone marrow disorders as well as a differential bone marrow cell counting and determination of reference intervals for diseases. PMID- 26679823 TI - Effect of pasture size on behavioural synchronization and spacing in German Blackface ewes (Ovis aries). AB - This study aims to assess plot size related changes in spacing and behavioural synchronization in a herd of 14 German Blackface ewes kept on three different pasture sizes: S (126m(2)), M (1100m(2)), and L (11,200m(2)). In direct field observations, behaviour and nearest neighbour distance were recorded individually. Additionally, interindividual and nearest neighbour distances were derived from aerial photographs of the herd taken on plot sizes S and M. Nearest neighbour distances <1m accounted for more than 60% of observations, and were more frequent on plot size L than on plot sizes S (Z=3.3; p<0.01) and M (Z=3.2; p<0.01). Average interindividual distances were significantly smaller on S (4.89+/-2.62m) than on M plots (5.99+/-3.06m; t=7.3; p<0.01). Synchronization tended to increase with plot size (K(S)=0.42; K(M)=0.52; K(L)=0.66), but was not accompanied by a concomitant increase in dispersion. Aerial photography proved a valuable tool in the analysis of spacing behaviour as intraindividual repeatability of the derived distances was highly significant (Kendall's W between 0.32 and 0.58; p<0.01). The sheep kept small distances on all plot sizes, thus the high degree of behavioural synchronization might be mainly attributed to the motivation for close proximity to any conspecific. PMID- 26679824 TI - Effects of several degrees of chronic social defeat stress on emotional and spatial memory in CD1 mice. AB - In the present study, the effects of several degrees of CSDS (Chronic Social Defeat Stress) on emotional and spatial memory in mice were evaluated in separate experiments. Male CD1 mice were randomly assigned to four experimental groups (n=10-12) for each experiment: NS (non-stressed), S5, S10 and S20 (5, 10 and 20 sessions of CSDS, respectively). The S groups underwent the corresponding number of agonistic encounters (10min each) over a 20-day period. 24h after the last session of CSDS, mice performed the inhibitory avoidance (Experiment 1) or the Morris water maze test (Experiment 2). In both experiments, animals were also evaluated in the elevated plus maze for 5min to obtain complementary measures of locomotor activity and emotionality. The results showed that the highest degree of CSDS had impairing effects on inhibitory avoidance, while there were no significant differences between groups in the water maze. The S20 group exhibited higher anxiety levels in the elevated plus maze. No variations in locomotor activity were observed in any experiment. In conclusion, CSDS has a greater impact on emotional memory than on spatial memory. These negative effects of CSDS on memory do not seem to be secondary to the motor or emotional effects of stress. PMID- 26679825 TI - A comparison of Google Glass and traditional video vantage points for bedside procedural skill assessment. AB - BACKGROUND: This pilot study assessed the feasibility of using first person (1P) video recording with Google Glass (GG) to assess procedural skills, as compared with traditional third person (3P) video. We hypothesized that raters reviewing 1P videos would visualize more procedural steps with greater inter-rater reliability than 3P rating vantages. METHODS: Seven subjects performed simulated internal jugular catheter insertions. Procedures were recorded by both Google Glass and an observer's head-mounted camera. Videos were assessed by 3 expert raters using a task-specific checklist (CL) and both an additive- and summative global rating scale (GRS). Mean scores were compared by t-tests. Inter-rater reliabilities were calculated using intraclass correlation coefficients. RESULTS: The 1P vantage was associated with a significantly higher mean CL score than the 3P vantage (7.9 vs 6.9, P = .02). Mean GRS scores were not significantly different. Mean inter-rater reliabilities for the CL, additive-GRS, and summative GRS were similar between vantages. CONCLUSIONS: 1P vantage recordings may improve visualization of tasks for behaviorally anchored instruments (eg, CLs), whereas maintaining similar global ratings and inter-rater reliability when compared with conventional 3P vantage recordings. PMID- 26679826 TI - Reliable assessment of operative performance. AB - BACKGROUND: There is no consensus regarding the number of intraoperative assessments required to reliably measure trainee performance. This study used generalizability theory (GT) to describe factors contributing to score variance and to estimate the number of assessments needed to achieve high standards of reliability. METHODS: While performing laparoscopic procedures, trainees were assessed by the attending surgeon using Global Operative Assessment of Laparoscopic Skills (GOALS). Data were collected prospectively (2-month intervals), assessing each trainee multiple times. Reliability coefficient was calculated using trainees, cases, and raters as factors. RESULTS: Eighteen trainees were included for a total of 65 assessments. Total variance in scores was accounted for as follows: 66.1% by trainees, 31.6% by the interaction between trainees and cases, and 2.3% by raters. At least 3 cases are required for reliable scores using GOALS. CONCLUSIONS: Trainees accounted for most of the variance in GOALS scores with a minimum of 3 cases required to improve the reliability of the scores obtained. These data may guide the implementation of performance assessments in surgical training programs. PMID- 26679827 TI - Examining the barriers to meaningful assessment and feedback in medical training. AB - BACKGROUND: Recent reports from both accreditation bodies in North America highlight problems with current assessment practices in postgraduate medical training. Previous work has shown that educators might be reluctant to report poor performance or fail underperforming trainees. This study explores the barriers perceived by medical educators to providing more meaningful assessment and feedback to trainees. METHODS: Semistructured interviews were conducted with 22 physician educators. Interviews were audiotaped and transcribed verbatim. Three researchers analyzed the transcripts using a grounded theory approach. RESULTS: Participants expressed a reluctance to provide poor assessments or feedback to trainees. Fifty-five percent of the participants reported passing trainees who could have benefited from additional training. Our data revealed a number of barriers which may account for these findings. Implementing more frequent formative assessments could help educators more effectively evaluate trainees and provide feedback, although a shift in the culture of medicine may be required. CONCLUSION: It is imperative that the barriers to effective assessment and feedback identified in this study be addressed to improve postgraduate medical training and enhance patient care. PMID- 26679828 TI - Knock-down of CIAPIN1 sensitizes K562 chronic myeloid leukemia cells to Imatinib by regulation of cell cycle and apoptosis-associated members via NF-kappaB and ERK5 signaling pathway. AB - CIAPIN1 (cytokine-induced apoptosis inhibitor 1) was recently identified as an essential downstream effector of the Ras signaling pathway. However, its potential role in regulating myeloid leukemia cells sensitivity to Imatinib remains unclear. In this study, we found depletion of CIAPIN1 inhibited proliferation and triggered more apoptosis of K562CML (chronic myeloid leukemia) cells with or without Imatinib treatment. Meanwhile, CIAPIN1 depletion decreased ERK5 phosphorylation and NF-kappaB activity. Importantly, treating CIAPIN1 depleted K562 cells with ERK5 signaling pathway specific inhibitor, XMD8-92, further inhibited proliferation and promoted apoptosis with or without Imatinib treatment. Treatment with the NF-kappaB specific inhibitor, Bay 11-7082, induced nearly the same inhibition of proliferation and promotion of apoptosis conferred by CIAPIN1 depletion as was observed with XMD8-92 treatment. Further, XMD8-92 and Bay 11-7082 synergistically inhibited proliferation and promoted apoptosis of CIAPIN1-depleted K562 cells with or without Imatinib treatment. The nude mice transplantation model was also performed to confirm the enhanced sensitivity of CIAPIN1-depleted K562 cells to Imatinib. Thus, our results provided a potential management by which CIAPIN1 knock-down might have a crucial impact on enhancing sensitivity of K562 cells to Imatinib in the therapeutic approaches, indicating that CIAPIN1 knock-down might serve as a combination with chemotherapeutical agents in leukemia diseases therapy. PMID- 26679829 TI - Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia. AB - BACKGROUND: Data regarding the viremia profile of chikungunya virus (CHIKV) infected patients especially during the pre-febrile period is limited. OBJECTIVE: To obtain virological kinetic data on CHIKV infections. STUDY DESIGN: A two-week community observation for dengue transmission was conducted in Bandung, Indonesia, from 2005 to 2009. Acute specimens from non-dengue febrile patients were screened by pan-alphavirus conventional RT-PCR. The positives were confirmed for CHIKV RNA by a specific RT-PCR followed by sequencing. Simultaneously these specimens were also cultured in Vero cells and tested for anti-CHIK IgM MAC ELISA. All the available serial specimens,including the pre-febrile specimens, from confirmed CHIK cases, were tested by virus isolation, RT-PCR, qRT-PCR, and CHIK IgM ELISA. RESULTS: There were five laboratory confirmed CHIK cases identified and studied. Among these, viremia was determined to extend from as early as 6 days prior to until 13 days post fever onset. Quantitative RT-PCR showed viremia peaked at or near onset of illness. CONCLUSION: In this study, individuals were identified with viremia prior to fever onset and extending beyond the febrile phase. This extended viremic phase has the potential to impact transmission dynamics and thus the public health response to CHIK outbreaks. PMID- 26679830 TI - Development of immunity following financial incentives for hepatitis B vaccination among people who inject drugs: A randomized controlled trial. AB - BACKGROUND: People who inject drugs (PWID) are at risk of hepatitis B virus (HBV) but have low rates of vaccination completion. The provision of modest financial incentives increases vaccination schedule completion, but their association with serological protection has yet to be determined. OBJECTIVE: To investigate factors associated with vaccine-induced immunity among a sample of PWID randomly allocated to receive AUD$30 cash following receipt of doses two and three ('incentive condition') or standard care ('control condition') using an accelerated 3-dose (0,7,21 days) HBV vaccination schedule. STUDY DESIGN: A randomised controlled trial among PWID attending two inner-city health services and a field site in Sydney, Australia, assessing vaccine-induced immunity measured by hepatitis B surface antibodies (HBsAb >= 10 mIU/ml) at 12 weeks. The cost of the financial incentives and the provision of the vaccine program are also reported. RESULTS: Just over three-quarters of participants - 107/139 (77%)- completed the vaccination schedule and 79/139 (57%) were HBsAb >= 10 mIU/ml at 12 weeks. Vaccine series completion was the only variable significantly associated with vaccine-induced immunity in univariate analysis (62% vs 41%, p<0.035) but was not significant in multivariate analysis. There was no statistically discernible association between group allocation and series completion (62% vs 53%). The mean costs were AUD$150.5, (95% confidence interval [CI]: 142.7-158.3) and AUD$76.9 (95% CI: 72.6-81.3) for the intervention and control groups respectively. CONCLUSION: Despite increasing HBV vaccination completion, provision of financial incentives was not associated with enhanced serological protection. Further research into factors which affect response rates and the optimal vaccination regimen and incentive schemes for this population are needed. PMID- 26679831 TI - Fatal tick-borne encephalitis in an immunosuppressed 12-year-old patient. PMID- 26679832 TI - The Relative Salience of Daily and Enduring Influences on Off-Job Reactions to Work Stress. AB - Work stress is an important determinant of employee health and wellness. The occupational health community is recognizing that one contributor to these relationships may be the presence of negative off-job reactivity to work, which we argue involves continued thoughts directed towards work (cognitive reactivity), continued negative mood stemming from work (affective reactivity), and the alteration of post-work behaviours in response to work factors (behavioural reactivity). We explored the relative contributions of daily work stressors, affective traits, and subjective job stress perceptions to negative off-job reactivity. These relationships were evaluated in a study of hospital nurses (n = 75), who completed trait measures and then provided self-assessments of daily work stress and off-job reactions for four work days. The results of several multilevel analyses indicated that a main-effects model best described the data when predicting cognitive, affective, and behavioural reactivity from daily work stressors, affective traits, and subjective job stress perceptions. A series of multilevel dominance analyses revealed that subjective job stress perceptions dominated the prediction of behavioural reactivity, while trait negative affect dominated the prediction of affective reactivity. Theoretical implications and the relative salience of daily and enduring contributors to negative off-job reactivity are discussed. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26679833 TI - Lagrangian methods for blood damage estimation in cardiovascular devices--How numerical implementation affects the results. AB - This paper evaluated the influence of various numerical implementation assumptions on predicting blood damage in cardiovascular devices using Lagrangian methods with Eulerian computational fluid dynamics. The implementation assumptions that were tested included various seeding patterns, stochastic walk model, and simplified trajectory calculations with pathlines. Post processing implementation options that were evaluated included single passage and repeated passages stress accumulation and time averaging. This study demonstrated that the implementation assumptions can significantly affect the resulting stress accumulation, i.e., the blood damage model predictions. Careful considerations should be taken in the use of Lagrangian models. Ultimately, the appropriate assumptions should be considered based the physics of the specific case and sensitivity analysis, similar to the ones presented here, should be employed. PMID- 26679834 TI - Recent Advances in Conjugated Polymer Materials for Disease Diagnosis. AB - The extraordinary optical amplification and light-harvesting properties of conjugated polymers impart sensing systems with higher sensitivity, which meets the primary demands of early cancer diagnosis. Recent advances in the detection of DNA methylation and mutation with polyfluorene derivatives based fluorescence resonance energy transfer (FRET) as a means to modulate fluorescent responses attest to the great promise of conjugated polymers as powerful tools for the clinical diagnosis of diseases. To facilitate the ever-changing needs of diagnosis, the development of detection approaches and FRET signal analysis are highlighted in this review. Due to their exceptional brightness, excellent photostability, and low or absent toxicity, conjugated polymers are verified as superior materials for in-vivo imaging, and provide feasibility for future clinical molecular-imaging applications. The integration of conjugated polymers with clinical research has shown profound effects on diagnosis for the early detection of disease-related biomarkers, as well as in-vivo imaging, which leads to a multidisciplinary scientific field with perspectives in both basic research and application issues. PMID- 26679835 TI - The SimplexaTM Group A Strep Direct Assay: a sample-to-answer molecular assay for the diagnosis of group A streptococcal pharyngitis. AB - The SimplexaTM Group A Strep Direct assay is intended for use on the Integrated Cycler for detection of Group A Streptococcus (GAS) directly from throat swabs that have not undergone nucleic acid extraction. A prospective study of 1352 samples in 4 geographically diverse sites showed an overall prevalence of GAS of 15.4%. The assay demonstrated 97.4% sensitivity and 95.2% specificity versus culture. The positive predictive value compared to culture was 72.7%. However, 46 out of 57 discrepant samples were Group A Strep positive when tested using a bi directional sequencing method illustrating the increased sensitivity of the assay compared to culture for detection of GAS. Rapid and accurate diagnosis of GAS allows for timely treatment to decrease complications of this prevalent organism that continues to cause substantial morbidity and mortality worldwide. PMID- 26679836 TI - The Linguistic Acoustic ThreaT Effect (LATTE): Screening tool for the impact of semantic threat in speech processing after a brain injury. PMID- 26679837 TI - Discovery of ethyl urea derivatives as inhibitors of islet amyloid polypeptide fibrillization and cytotoxicity. AB - Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, thereby furthering type 2 diabetes disease progression. Further discovery of new molecules is needed to create a diverse set of molecules that impede pancreatic amyloidosis. We have recently designed and synthesized N phenyl-N'-(2-ethyl)ureas (EU) that are non-cytotoxic small molecules, to evaluate the role of the aryl-substituted moiety on the inhibition of hIAPP fibrillization. Several EUs were tested in vitro for their anti-amyloidogenic activity using the fluorometric ThT assay, the photo-induced cross-linking (PIUCP) assay, and cell survival assay in pancreatic MIN-6 cells. EU-362 and EU 418 were able to significantly inhibit the formation of hIAPP fibrils and protected cells from amyloid cytotoxic effects. Our results suggest that increasing the nucleophilic potency of the aryl moiety significantly enhances the anti-amyloidogenic activity of the molecules. PMID- 26679838 TI - Current reprogramming systems in regenerative medicine: from somatic cells to induced pluripotent stem cells. AB - Induced pluripotent stem cells (iPSCs) paved the way for research fields including cell therapy, drug screening, disease modeling and the mechanism of embryonic development. Although iPSC technology has been improved by various delivery systems, direct transduction and small molecule regulation, low reprogramming efficiency and genomic modification steps still inhibit its clinical use. Improvements in current vectors and the exploration of novel vectors are required to balance efficiency and genomic modification for reprogramming. Herein, we set out a comprehensive analysis of current reprogramming systems for the generation of iPSCs from somatic cells. By clarifying advantages and disadvantages of the current reprogramming systems, we are striding toward an effective route to generate clinical grade iPSCs. PMID- 26679839 TI - Endoplasmic reticulum membrane-bound MoSec62 is involved in the suppression of rice immunity and is essential for the pathogenicity of Magnaporthe oryzae. AB - Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) constitutes the first line of plant inducible immunity. As an important step of plant colonization, phytopathogens have to suppress PTI, and secreted effectors are therefore co-evolved and deployed. In this study, we characterized the function of MoSec62 of Magnaporthe oryzae, the causal agent of the destructive rice blast. MoSec62 encodes a homologue of Sec62p, a yeast endoplasmic reticulum (ER) membrane transporter for precursors of secretory proteins. We showed that a T-DNA insertion into the promoter region of MoSec62, causing a disturbance to the up regulation of MoSec62 expression during blast invasion, resulted in a complete loss of blast virulence of the mutant, M1575. Both 3,3'-diaminobenzidine (DAB) staining of the infected rice leaves and expression analysis revealed that the infectious attempt by the mutant led to strong defence responses of rice. Consistently, in transcriptomic analysis of rice leaves subject to blast inoculation, a battery of defence responses was found to be induced exclusively on M1575 challenge. For further exploration, we tested the pathogenicity on a highly susceptible rice variety and detected the accumulation of Slp1, a known PTI suppressor. Both results suggested that the mutant most likely failed to overcome rice PTI. In addition, we showed that MoSec62 was able to rescue the thermosensitivity of a yeast Deltasec62, and the MoSec62-GFP fusion was co localized to the ER membrane, both suggesting the conservation of Sec62 homologues. In conclusion, our data indicate that MoSec62, probably as an ER membrane transporter, plays an essential role in antagonizing rice defence at the early stages of blast invasion. PMID- 26679840 TI - Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine. AB - Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activities of ROS in a model of Apc deletion, where loss of the Wnt target gene Myc both rescues APC loss and prevents ROS accumulation. Following APC loss, Myc has been shown to up-regulate RAC1 to promote proliferative ROS through NADPH oxidase (NOX). However, APC loss also increased the expression of TIGAR, which functions to limit ROS. To explore this paradox, we used three-dimensional (3D) cultures and in vivo models to show that deletion of TIGAR increased ROS damage and inhibited proliferation. These responses were suppressed by limiting damaging ROS but enhanced by lowering proproliferative NOX-derived ROS. Despite having opposing effects on ROS levels, loss of TIGAR and RAC1 cooperated to suppress intestinal proliferation following APC loss. Our results indicate that the pro- and anti-proliferative effects of ROS can be independently modulated in the same cell, with two key targets in the Wnt pathway functioning to integrate the different ROS signals for optimal cell proliferation. PMID- 26679842 TI - Delayed diagnosis of glucagonoma syndrome: a case report. PMID- 26679841 TI - BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance. AB - Melanoma can switch between proliferative and invasive states, which have identifying gene expression signatures that correlate with good and poor prognosis, respectively. However, the mechanisms controlling these signatures are poorly understood. In this study, we identify BMI1 as a key determinant of melanoma metastasis by which its overexpression enhanced and its deletion impaired dissemination. Remarkably, in this tumor type, BMI1 had no effect on proliferation or primary tumor growth but enhanced every step of the metastatic cascade. Consistent with the broad spectrum of effects, BMI1 activated widespread gene expression changes, which are characteristic of melanoma progression and also chemoresistance. Accordingly, we showed that up-regulation or down regulation of BMI1 induced resistance or sensitivity to BRAF inhibitor treatment and that induction of noncanonical Wnt by BMI1 is required for this resistance. Finally, we showed that our BMI1-induced gene signature encompasses all of the hallmarks of the previously described melanoma invasive signature. Moreover, our signature is predictive of poor prognosis in human melanoma and is able to identify primary tumors that are likely to become metastatic. These data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance of melanoma. PMID- 26679852 TI - CD8 T-Cell Lymphocytosis and Associated Clinical Syndromes in HIV-Infected Patients. AB - An inverted CD4:CD8 T lymphocyte ratio is frequently observed in individuals infected with HIV. A subset of these individuals develops an exuberant and persistent CD8 T-cell lymphocytosis response to HIV infection that may occur despite virologic suppression on treatment and has been associated with adverse clinical effects and disorders. This review describes clinical syndromes that have been reported primarily in HIV-infected individuals with CD8 T-cell lymphocytosis including their presentation, management, and clinical outcomes where known. PMID- 26679853 TI - Nuke-Sparing Regimens for the Long-Term Care of HIV Infection. AB - With the efficacy of antiretroviral therapy already guaranteed for all practical purposes, the main objective in the management of HIV-positive patients has moved to reduce and prevent potential long-term toxicities. Nucleos(t)ide-sparing regimens could enable the best to address this issue, with a wide range of current options that may allow adaptation to distinct patient populations. Monotherapy with boosted darunavir and lopinavir has been safely prescribed as maintenance therapy to stable patients on stable antiretroviral therapy without nadir CD4 count < 200/mm3, low-level baseline viremia, prolonged viral suppression, and without prior virologic failure. In the presence of all these requirements, dual therapy with lamivudine plus boosted lopinavir or atazanavir has been shown to be equivalent to standard triple therapy. Other nucleoside sparing dual therapies, especially using raltegravir combined with boosted darunavir or lopinavir and etravirine or rilpivirine in combination with boosted darunavir, have performed well as simplification strategies or rescue interventions in a wide spectrum of patients as long as drug resistance was absent. With current economical constrains, nuke-sparing regimens have attained a degree of maturity that makes it possible to anticipate that they will play an important role in the optimization of antiretroviral therapy in the near future. PMID- 26679854 TI - Structural MRI Biomarkers of Mild Cognitive Impairment from Young Elders to Centenarians. AB - Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. METHODS: 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in individuals <85 and those >=85 years. RESULTS: aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and >=85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortices in <85 years, and the hippocampus, pars triangularis and temporal pole in >=85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes. CONCLUSIONS: Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly individuals. The structures that best distinguish aMCI from CN differ in those <85 from those >=85, suggesting different neuropathological underpinnings of cognitive impairment in the very old. PMID- 26679855 TI - Defining the earliest pathological changes of Alzheimer's disease. AB - The prospects for effectively treating well-established dementia, such as Alzheimer's disease (AD), are slim, due to the destruction of key brain pathways that underlie higher cognitive function. There has been a substantial shift in the field towards detecting conditions such as AD in their earliest stages, which would allow preventative or therapeutic approaches to substantially reduce risk and/or slow the progression of disease. AD is characterized by hallmark pathological changes such as extracellular Abeta plaques and intracellular neurofibrillary pathology, which selectively affect specific subclasses of neurons and brain circuits. Current evidence indicates that Abeta plaques begin to form many years before overt dementia, a gradual and progressive pathology which offers a potential target for early intervention. Early Abeta changes in the brain result in localized damage to dendrites, axonal processes and synapses, to which excitatory synapses and the processes of projection neurons are highly vulnerable. Abeta pathology is replicated in a range of transgenic models overexpressing mutant human familial AD genes (e.g. APP and presenilin 1). Studying the development of aberrant regenerative and degenerative changes in neuritic processes associated with Abeta plaques may represent the best opportunity to understand the relationship between the pathological hallmarks of AD and neuronal damage, and to develop early interventions to prevent, slow down or mitigate against Abeta pathology and/or the neuronal alterations that leads to cognitive impairment. PMID- 26679856 TI - The Relationship Between Plasma Abeta Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study. AB - OBJECTIVES: Determine whether (1) a relationship exists between plasma amyloid beta (Abeta)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Abeta peptide levels differ between apolipoprotein E (APOE) epsilon4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Abeta levels. METHODS: Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE epsilon4 genotyped. Plasma levels of Abeta1-40 and 1-42 were quantified using ELISA. RESULTS: Wave1 plasma levels of Abeta peptides and Abeta1-42/1-40 ratio were lower in aMCI and AD, and Abeta1-42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities. The relationships of Abeta1-40 and Abeta1-42 were predominantly observed in epsilon4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Abeta1-42 and the ratio measure. CONCLUSION: Plasma Abeta levels and the Abeta1-42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Abeta1-40 and Abeta1-42 in epsilon4 carriers and non-carriers. These data support the Abeta sink model of AD pathology, and suggest that plasma Abeta measures may serve as biomarkers of AD. PMID- 26679857 TI - SS31, a Small Molecule Antioxidant Peptide, Attenuates beta-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice. AB - Mitochondrial dysfunction, oxidative stress and beta -amyloid (Abeta) formation are thought to cause neuronal and synaptic degeneration underlying cognitive decline in Alzheimer's disease (AD). The senescence-accelerated mouse-prone 8 (SAMP8) mice have been used as an animal model for mechanistic and translational research for AD. In the present study we characterized mitochondrial and synaptic alterations in SAMP8 mice relative to SAMR1control mice and explored a protective effect of the small molecule peptide SS31, a cell membrane penetrant antioxidant, on mitochondrial and synaptic protein integrity as well as cognitive performance. Electron microscopic analysis revealed mitochondrial/synaptic deterioration in 10 months-old SAMP8 relative to SAMR1 mice, with the changes in the former rescued following 8 weeks treatment with SS31 (5 mg/kg/day, i.p.). Elevation of Abeta42, mitochondrial fission protein (DLP1, Fis1) and matrix protein cyclophilin D (CypD), and reductions of mitochondrial fusion protein (Mfn2) and synaptic (i.e., synaptophysin, postsynaptic density protein 95 and growth associated protein 43) proteins, were detected in hippocampal lysates in SAMP8 mice relative to SAMR1. The above altered protein expressions in the SAMP8 mouse brain were restored with the SS31 treatment. Moreover, the SS31 treatment rescued learning and memory deficits detected in 10 month-old SAMP8 mice. Together, the findings suggest that this mitochondria-targeting antioxidant peptide may be of potential utility for AD therapy, with its pharmacological efficacy involves lowering of central Abeta levels and protection of mitochondrial homeostasis and synaptic integrity, which may help slow down cognitive decline. PMID- 26679858 TI - Testosterone, Estradiol, and Sex Hormone-Binding Globulin in Alzheimer's Disease: A Meta-Analysis. AB - BACKGROUND: Previous studies suggested that plasma sex hormones may be implicated in the pathogenesis of Alzheimer's disease (AD). However, the relationship between sex hormones and AD remains unclear. OBJECTIVE: To systematically review and quantitatively analyze studies observing plasma total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels among AD patients. METHODS: Medline, EMBASE, the Cochrane Library, and PsycINFO were searched for studies published prior to March 28(th), 2014. Published studies that reported plasma levels of TT, E2, and SHBG in AD and matched controls were included in the present meta-analysis. RESULTS: Meta-analysis was performed using the random effects model, expressing continuous outcomes as the mean difference (MD) between AD and control populations. The 95% confidence intervals (CI) were also calculated. No differences were found in plasma levels of TT and E2 between AD and matched controls (TT MD -0.17 nmol/l, 95% CI -0.54, 0.20; E2 MD -1.16 pmol/l, 95% CI -9.85, 6.83). Plasma levels of SHBG were significantly increased in AD patients compared to healthy controls (SHBG MD 12.94 nmol/l, 95% CI 2.68, 23.20). CONCLUSION: Patients with AD had higher plasma levels of SHBG. The up-regulated levels of plasma SHBG show preliminary supportive evidence that SHBG and the bioavailability of functional sex hormones in plasma may be linked to the pathogenesis of AD. PMID- 26679859 TI - PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration. AB - The unfolded protein response (UPR) plays a vital role in maintaining cell homeostasis as a consequence of endoplasmic reticulum (ER) stress. However, prolonged UPR activity leads to cell death. This time-dependent dual functionality of the UPR represents the adaptive and cytotoxic pathways that result from ER stress. Chronic UPR activation in systemic and neurodegenerative diseases has been identified as an early sign of cellular dyshomeostasis. The Protein Kinase R-like ER Kinase (PERK) pathway is one of three major branches in the UPR, and it is the only one to modulate protein synthesis as an adaptive response. The specific identification of prolonged PERK activity has been correlated with the progression of disorders such as diabetes, Alzheimer's disease, and cancer, suggesting that PERK plays a role in the pathology of these disorders. For the first time, the term "PERK-opathies" is used to group these diseases in which PERK mediates detriment to the cell culminating in chronic disorders. This article reviews the literature documenting links between systemic disorders with the UPR, but with a specific emphasis on the PERK pathway. Then, articles reporting links between the UPR, and more specifically PERK, and neurodegenerative disorders are presented. Finally, a therapeutic perspective is discussed, where PERK interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders. PMID- 26679860 TI - Glutamate and Mitochondria: Two Prominent Players in the Oxidative Stress-Induced Neurodegeneration. AB - The aetiology of major neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is still unknown, but increasing evidences suggest that glutamate and mitochondria are two prominent players in the oxidative stress (OS) process that underlie these illnesses. Although AD and PD have distinct pathological and clinical features, OS is a common mechanism contributing to neuronal damage. Glutamate is an important neurotransmitter in neurons and glial cells and is strongly dependent on calcium homeostasis and on mitochondrial function. In the present work we focused on glutamate- induced calcium signaling and its relation to the mitochondrial dysfunction with cell death processes. In addition, we have discussed how alterations in this pathway may lead or aggravate the neurodegenerative diseases. Finally, this review aims to stimulate further studies on this issue and thereby engage a new perspective regarding the design of possible therapeutic agents or the identification of biomarkers. PMID- 26679861 TI - Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage. AB - Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Amyloid-beta peptide (Abeta) forms senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks of AD neuropathology. Evidence support the involvement of immune system in AD progression and current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune components in the neurodegenerative process. Pathologically, immune system components have been detected in the brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates with disease progression. However, patients with AD present significantly lower levels of antibody immunoreactivity against Abeta in serum and CSF than healthy controls suggesting that a depletion of such patrolling system is involved in the deposition of toxic aggregates in AD. Within this frame, incomplete and often controversial results are reported about CNS immune/ autoimmune responses during AD, and a better comprehension of such processes is needed. Our research will aim to shed light on the nature and potential role of autoantibodies in CSF and serum from AD and amnestic mild cognitive impairment (aMCI) patients compared to healthy subjects by using an immunoproteomics approach. Our method allows recognition of natural occurring antibodies by the identification of brain antigen targeted by human IgGs. Overall our data reveal that the alterations of autoantibodies profile both in CSF and serum follow disease staging and progression. However, we demonstrate a fair overlap between CSF and serum suggesting the existence of different immunogenic events. Interestingly, CSF autoantibodies recognized, among others, key players of energy metabolic pathway, including glycolysis and TCA cycle, found oxidatively modified in AD brain studies. These data suggest a potential casual sequence between oxidative damage at brain level, autoantibodies presence in CSF and reduced energy metabolism of AD patients. PMID- 26679862 TI - Correction to Multiconfiguration Pair-Density Functional Theory: Barrier Heights and Main Group and Transition Metal Energetics. PMID- 26679863 TI - Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation. AB - L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid beta (Abeta) stimulates platelet aggregation, we studied whether L5 and Abeta function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Abeta, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Abeta release via IkappaB kinase 2 (IKK2). Furthermore, L5+Abeta synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IkappaBalpha, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-kappaB (NF-kappaB). Injecting L5+Abeta shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Abeta-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-kappaB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies. PMID- 26679866 TI - How I treat extramedullary myeloma. AB - Extramedullary myeloma (EMM) is defined by the presence of plasma cells (PCs) outside the bone marrow in a patient with multiple myeloma (MM). Using sensitive imaging techniques including magnetic resonance imaging and positron emission tomography/computed tomography, EMM may be found in up to 30% of MM patients across the overall disease course. The molecular mechanisms underlying the hematogenous spread of PCs outside the bone marrow are only partially known and involve hypoxia and an altered expression of adhesion molecules. Extramedullary disease is associated with adverse prognostic factors (ie, high lactate dehydrogenase level, 17p deletion, and high-risk gene expression profile). The prognosis of EMM is poor, and the median overall survival of patients who experience an extramedullary relapse is <6 months. The adverse prognosis is less pronounced in patients with bone-related plasmacytomas than in those with hematogenous EMM. EMM patients should be considered as having high-risk myeloma and treated accordingly. However, EMM clinical situations are extraordinarily heterogeneous, and their management is particularly challenging. In the present review, a case-and-comment format is used to describe our approach to the management of EMM. PMID- 26679865 TI - Discordant bone marrow involvement in non-Hodgkin lymphoma. AB - A discordant lymphoma occurs where 2 distinct histologic subtypes coexist in at least 2 separate anatomic sites. Histologic discordance is most commonly observed between the bone marrow (BM) and lymph nodes (LNs), where typically aggressive lymphoma is found in a LN biopsy with indolent lymphoma in a BM biopsy. Although the diagnosis of discordance relied heavily on histopathology alone in the past, the availability of flow cytometry and molecular studies have aided the identification of this entity. The true prevalence and clinical ramifications of discordance remain controversial as available data are principally retrospective, and there is therefore little consensus to guide optimal management strategies. In this review, we examine the available literature on discordant lymphoma and its outcome, and discuss current therapeutic approaches. Future studies in discordant lymphoma should ideally focus on a large series of patients with adequate tissue samples and incorporate molecular analyses. PMID- 26679864 TI - Pomalidomide reverses gamma-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors. AB - Current therapeutic strategies for sickle cell anemia are aimed at reactivating fetal hemoglobin. Pomalidomide, a third-generation immunomodulatory drug, was proposed to induce fetal hemoglobin production by an unknown mechanism. Here, we report that pomalidomide induced a fetal-like erythroid differentiation program, leading to a reversion of gamma-globin silencing in adult human erythroblasts. Pomalidomide acted early by transiently delaying erythropoiesis at the burst forming unit-erythroid/colony-forming unit-erythroid transition, but without affecting terminal differentiation. Further, the transcription networks involved in gamma-globin repression were selectively and differentially affected by pomalidomide including BCL11A, SOX6, IKZF1, KLF1, and LSD1. IKAROS (IKZF1), a known target of pomalidomide, was degraded by the proteasome, but was not the key effector of this program, because genetic ablation of IKZF1 did not phenocopy pomalidomide treatment. Notably, the pomalidomide-induced reprogramming was conserved in hematopoietic progenitors from individuals with sickle cell anemia. Moreover, multiple myeloma patients treated with pomalidomide demonstrated increased in vivo gamma-globin levels in their erythrocytes. Together, these data reveal the molecular mechanisms by which pomalidomide reactivates fetal hemoglobin, reinforcing its potential as a treatment for patients with beta hemoglobinopathies. PMID- 26679867 TI - Interaction of Hereditary Thrombophilia and Traditional Cardiovascular Risk Factors on the Risk of Arterial Thromboembolism: Pooled Analysis of Four Family Cohort Studies. AB - BACKGROUND: Hereditary thrombophilia is associated with a slightly increased risk of arterial thromboembolism (ATE). Whether hereditary thrombophilia interacts with traditional cardiovascular risk factors on the risk of ATE has yet to be established. METHODS AND RESULTS: A total of 1891 individuals belonging to 4 family cohorts from the Netherlands were included in the analyses. Five hereditary thrombophilic defects, including factor V Leiden, prothrombin G20210A defect, and deficiencies of the natural anticoagulants (ie, antithrombin, protein C, and protein S), were assessed, and data on risk factors and previous ATE were collected. Thrombophilia was associated with elevated risk of ATE (hazard ratio =1.74, 95% confidence interval, 1.18-2.58; P=0.005). Overall, the association of thrombophilia with ATE tended to be stronger in the presence of traditional cardiovascular risk factors, especially the synergistic effect of thrombophilia with diabetes mellitus was striking (hazard ratio of thrombophilia-ATE association was 1.41 in nondiabetics versus 8.11 in diabetics). Moreover, the association of thrombophilia with ATE tended to be stronger in females and before the age of 55 years as compared with males and individuals >55 years of age, respectively. CONCLUSIONS: Thrombophilia is associated with ATE. This association may be stronger in the presence of traditional cardiovascular risk factors in particular in individuals with diabetes mellitus. Future studies on thrombophilia ATE risk should focus on high-risk populations with high prevalence of traditional cardiovascular risk factors. PMID- 26679868 TI - Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome. AB - BACKGROUND: The HLA-DRB1*01 allele of the human leukocyte antigen has been associated with acute coronary syndrome. Genome-wide association studies have revealed associations with human leukocyte antigen and non-human leukocyte antigen genes of 3 major histocompatibility complex gene classes but not at allelic level. METHODS AND RESULTS: We conducted a large-scale genetic analysis on a case-control cohort comprising 5376 acute coronary syndrome cases and 4852 unrelated controls from 4 populations of 2 European countries. We analyzed the risk candidate allele of HLA-DRB1*01 by genomic real-time polymerase chain reaction together with high-density single nucleotide polymorphisms of the major histocompatibility complex to precisely identify risk loci for acute coronary syndrome with effective clinical implications. We found a risk haplotype for the disease containing single nucleotide polymorphisms from BTNL2 and HLA-DRA genes and the HLA-DRB1*01 allele. The association of the haplotype appeared in 3 of the 4 populations, and the direction of the effect was consistent in the fourth. Coronary samples from subjects homozygous for the disease-associated haplotype showed higher BTNL2 mRNA levels (r=0.760; P<0.00001).We localized, with immunofluorescence staining, BTNL2 in CD68-positive macrophages of the coronary artery plaques. In homozygous cases, BTNL2 blocking, in T-cell stimulation assays, enhanced CD4(+)FOXP3(+) regulatory T cell proliferation significantly (blocking versus nonblocking; P<0.05). CONCLUSIONS: In cases with the risk haplotype for acute coronary syndrome, these results suggest involvement of enhanced immune reactions. BTNL2 may have an inhibitory effect on FOXP3(+) T cell proliferation, especially in patients homozygous for the risk alleles. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov; Unique Identifier: NCT00417534. PMID- 26679869 TI - Multimodal Versus Patient-Controlled Analgesia After an Anterior Cervical Decompression and Fusion. AB - STUDY DESIGN: Retrospective analysis of a prospectively maintained surgical registry. OBJECTIVE: To compare postoperative narcotic consumption between multimodal analgesia (MMA) and patient-controlled analgesia (PCA) after an anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Studies suggest that a multimodal approach to pain management leads to decreased pain and morphine consumption after total joint arthroplasty and lumbar spinal procedures. Patients and surgeons would benefit from knowing whether a multimodal approach to pain management is superior to PCA for ACDF. METHODS: A retrospective cohort study of ACDF patients receiving either MMA or PCA was conducted. Inpatient narcotic consumption, pain scores, nausea/vomiting, hospital length of stay, and narcotic dependence during the months after surgery were compared between MMA and PCA. RESULTS: A total of 239 patients met inclusion criteria. Of these, 55 (23.0%) received MMA and 184 (77.0%) received PCA. Patients who received MMA had a lower rate of inpatient narcotic consumption (2.5 OME/h vs. 5.8 OME/h, P < 0.001) were less likely to experience nausea/vomiting during the hospitalization (5.5% vs. 37.5%, P < 0.001), and had a shorter hospital length of stay (27.3 vs. 40.1 h, P < 0.001). However, there was no difference between groups in mean visual analogue pain scale during postoperative day zero (4.7 for MMA vs. 5.2 for PCA, P = 0.126) or during postoperative day one (4.1 for MMA vs. 4.1 for PCA, P = 0.937). In addition, there was no difference in the rate of narcotic dependence at the first (P = 0.626) or second (P = 0.480) postoperative visits. CONCLUSION: These data suggest that MMA results in lower narcotic consumption than PCA after an ACDF. This difference is associated with a shorter inpatient stay and a decrease in postoperative nausea/vomiting. Critically, MMA and PCA appear to provide similar postoperative analgesia. LEVEL OF EVIDENCE: 3. PMID- 26679870 TI - Comparing Nonrandomized Observational Studies With Randomized Controlled Trials in Cervical Disc Arthroplasty: A Meta-analysis. AB - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare the treatment effects of observational studies versus randomized controlled trials (RCTs) in cervical disc arthroplasty. SUMMARY OF BACKGROUND DATA: RCTs can be logistically challenging and sometimes insufficiently generalizable; well designed observational studies have been suggested as an alternative. We hypothesized that treatment effects of observational studies in cervical disc arthroplasty are similar to those of RCTs. METHODS: We searched electronic database from 2000 to 2014. The Neck Disability Index (NDI) was the primary outcome from which the standardized pre-and-post mean difference (Hedges's g) was determined. Meta-analysis was performed to compare Hedges's g from observational studies to that of RCTs. Potential moderator variables including study quality, age, gender, industry sponsorship, location by continent, and disc types were also collected and analyzed. Observational studies were further stratified into prospective and retrospective, and they were compared to each other as well as to RCTs. RESULTS: We identified nine RCTs, 28 observational studies, and one hybrid study for meta-analysis. NDI Hedges's g was 2.15 for RCTs and 2.03 for observational studies, which was not significant (P = 0.416). No significant difference was found in secondary outcomes. However, after further stratification, prospective observational studies had less treatment effect in Visual Analog Scale neck compared with that of RCTs (1.60 vs. 2.11, P = 0.006). RCTs recruited younger patients (44.1 vs. 45.6, P = 0.008) with worse NDI at baseline (54.30 vs. 46.92, P < 0.001). Patients treated with ProDisc-C showed less standardized improvement on the NDI compared with the patients treated with Prestige (1.41 vs. 2.48, P = 0.026). CONCLUSION: Prospective observational studies that utilize the same features of RCTs such as inclusion and exclusion criteria validated clinical outcomes, and statistical methods can provide valuable information about the treatment effects on a generalizable population. LEVEL OF EVIDENCE: 4. PMID- 26679871 TI - Proportion of Expectations Fulfilled: A New Method to Report Patient-centered Outcomes of Spine Surgery. AB - STUDY DESIGN: Prospective lumbar and cervical surgery cohorts. OBJECTIVE: Compare fulfillment of expectations with traditional global outcomes and provide evidence for its validity. SUMMARY OF BACKGROUND DATA: New lumbar and cervical spine surgery Expectations Surveys can be used to measure fulfillment of expectations and their performance should be compared with existing outcomes. METHODS: Three hundred thirty-six lumbar and 133 cervical spine surgery patients preoperatively completed valid 20-item Expectations Surveys measuring symptoms, function, and psychological well-being. Approximately 2 years postoperatively patients rated how much improvement they received for each item. The proportion of expectations fulfilled was compared with traditional outcomes, including global satisfaction and change in standard spine questionnaires, with correlation coefficients (r) and areas under receiver operator characteristic curves (AUC). RESULTS: Ninety percent of lumbar patients had some expectations fulfilled (24% had all expectations fulfilled completely or exceeded). The mean proportion of expectations fulfilled was 0.66 and was associated with satisfaction (r = 0.73 (95% CI 0.68-0.78); AUC = 0.92 (95% CI 0.89-0.95) (P < 0.0001)). Based on the association with satisfaction, a clinically important proportion of expectations fulfilled for lumbar surgery is approximately 0.60 (sensitivity 0.90, specificity 0.79).Ninety-one percent of cervical patients had some expectations fulfilled (31% had all expectations fulfilled completely or exceeded). The mean proportion of expectations fulfilled was 0.78 and was associated with satisfaction (r = 0.62 (95% CI 0.50-0.72); AUC = 0.92 (95% CI 0.87-0.97) (P < 0.0001)). Based on the association with satisfaction, a clinically important proportion of expectations fulfilled for cervical surgery is approximately 0.62 (sensitivity 0.91, specificity 0.80). CONCLUSION: The proportion of expectations fulfilled is a new patient-centered outcome that measures results of spine surgery. Unique features of this novel outcome are that it requires prospectively acquired pre- and postoperative data, provides details about in what ways patients believe surgery did and did not meet goals, and offers surgeons opportunities to address unfilled expectations directly. LEVEL OF EVIDENCE: 1. PMID- 26679872 TI - Biomechanical Analysis of an S1 Pedicle Screw Salvage Technique via a Superior Articulating Process Entry Point. AB - STUDY DESIGN: Biomechanical, cadaveric study. OBJECTIVE: To compare the fixation strength of a novel S1 pedicle screw insertion technique in a revision setting to a standard S1 pedicle screw and an L5 pedicle screw. SUMMARY OF BACKGROUND DATA: Fusions to the sacrum remain a difficult clinical challenge. Very few salvage techniques exist when a nonunion occurs. METHODS: The biomechanical integrity of three screw fixations, L5 pedicle screws, a standard S1 pedicle screw, and an S1 pedicle screw placed via a superior articulating process entry point (SAP S1), was characterized by performing pullout tests using cadaveric specimens including L5 and sacrum. RESULTS: SAP S1 constructs (735.5 +/- 110.1 N/mm) were significantly stiffer than standard S1 (P = 0.005) and L5 (P = 0.02) constructs. There was no statistically significant difference between the L5 constructs and the standard S1 constructs for linear stiffness. There was no statistical difference between the three fixations for yield load, displacement at yield load, and energy absorbed to yield load.The ultimate pullout force for the SAP S1 was statistically higher than the standard S1 (1213.7 +/- 579.6 vs. 478.6 +/- 452.9 N; P = 0.004). Displacement at ultimate load was significantly greater for L5 screw fixation (3.3 +/- 1.1 mm) compared to the other two constructs. Both the L5 (2277.4 +/- 1873.3 N-mm) and SAP S1 (2628.2 +/- 2054.4 N-mm) constructs had significantly greater energy absorbed to ultimate load than the standard S1 construct (811.7 +/- 937.6 N-mm), but there was no statistical difference between the L5 and SAP S1 constructs. CONCLUSION: S1 pedicle screw fixation via an SAP entry point provides biomechanical advantages compared to screws placed via the standard S1 or L5 entry point and may be a viable option for revision of a failed L5-S1 fusion with a compromised standard S1 entry point. LEVEL OF EVIDENCE: N/A. PMID- 26679873 TI - Incidence and Risk Factors for Pneumonia After Posterior Lumbar Fusion Procedures: An ACS-NSQIP Study. AB - STUDY DESIGN: Retrospective study of data collected prospectively by the American College of Surgeons National Surgical Quality Improvement Program. OBJECTIVE: To determine the incidence and risk factors for development of pneumonia after posterior lumbar fusion (PLF). SUMMARY OF BACKGROUND DATA: Postoperative pneumonia has important clinical consequences for patients and the health care system. Few studies have examined pneumonia after spinal fusion procedures. METHODS: Patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent PLF during 2005 to 2013 were included. The primary outcome was a diagnosis of pneumonia within the first 30 postoperative days. Independent risk factors for the development of postoperative pneumonia were identified using multivariate regression. Rates of sepsis and mortality were compared between patients who did and did not develop pneumonia using multivariate regression that adjusted for all demographic, comorbidity, and procedural characteristics. RESULTS: A total of 12,428 patients undergoing PLF were identified. The incidence of pneumonia was 0.59%. Independent risk factors for the development of pneumonia were chronic obstructive pulmonary disease (relative risk [RR] = 2.7, P = 0.006), steroid use (RR = 2.6, P = 0.017), non insulin-dependent diabetes mellitus (DM) (RR = 2.4, P = 0.003), insulin-dependent DM (RR = 2.9, P = 0.005), and greater number of operative levels (two level: RR = 1.7, P = 0.033; three level: RR = 2.7, P = 0.007). Patients who developed pneumonia had a higher rate of sepsis (15.1% vs. 0.8%, adjusted RR = 14.5, P < 0.001) and mortality (2.7% versus 0.1%, adjusted RR = 27.0, P < 0.001) than other patients. Of all sepsis cases and postoperative mortalities, 10.5% and 18.2% occurred in patients who had developed pneumonia, respectively. CONCLUSION: Pneumonia occurs in approximately 1 in 200 patients after PLF. Pneumonia plays a significant role in the development of sepsis and mortality, with 10% of sepsis and 20% of mortality cases occurring in patients who had developed pneumonia. Patients with chronic obstructive pulmonary disease, steroid use, DM, and a greater number of operative levels are at greater risk. These patients should be counseled, monitored, and targeted with preventative interventions accordingly. LEVEL OF EVIDENCE: 3. PMID- 26679874 TI - Surgery for Degenerative Lumbar Scoliosis: The Development of Appropriateness Criteria. AB - STUDY DESIGN: The RAND/UCLA Appropriateness Method is a well-established means of developing criteria for assessing the appropriateness of surgery in specific subpopulations. It involves a systematic review of the literature and ratings by a multidisciplinary panel of national experts. OBJECTIVE: To evaluate the appropriateness of surgical interventions for degenerative lumbar scoliosis (DLS), including identifying clinical characteristics that influence when surgery is inappropriate, appropriate, or necessary, and which procedures are preferable. SUMMARY OF BACKGROUND DATA: DLS presents with diverse clinical symptoms and radiographic findings. Variability exists in both nonoperative and operative management. The appropriateness of surgery, and of specific surgical procedures, has not been defined for this important pathology of the aging spine. METHODS: We selected a panel of 11 experts, including surgical specialists from multiple disciplines. Next, we systematically reviewed relevant literature. Finally, in a three-round, modified-Delphi process, panelists rated the appropriateness and necessity of five different surgical procedures (dependent variables) on a nine point scale for 260 different clinical scenarios that stratified patients according to age, medical comorbidities, symptoms, signs, and radiographic variables (independent variables). RESULTS: The 59 eligible studies identified via the systematic review were generally small or used weak designs. Panelists judged that surgery was generally appropriate for patients with at least moderate symptoms and larger or progressive deformities, moderate spinal or foraminal stenosis, or sagittal plane imbalance. Surgery was generally inappropriate for mild symptoms and smaller stable deformities, without sagittal imbalance or moderate stenosis, particularly among patients with advanced age and multiple comorbidities. For patients with larger or progressive deformities, imbalance, or severe multilevel stenosis, more extensive fusion and deformity correction procedures were generally preferred. CONCLUSION: Defining the appropriateness of surgery for patients with DLS will be useful to improve evidence-based clinical decision making as well as the consistency and quality of care for patients with DLS. LEVEL OF EVIDENCE: 3. PMID- 26679875 TI - Worldwide Research Productivity in the Field of Minimally Invasive Spine Surgery: A 20-year Survey of Publication Activities. AB - : MINI: The time trend for the number of minimally invasive spine surgery articles showed a significant increase over time with an average of 93.23 articles per year. Among all related journals, Spine published the largest number of articles in minimally invasive spine surgery research and was the most popular one in the top five countries. STUDY DESIGN: Bibliometric analysis. OBJECTIVE: This study aimed to reveal the characteristics of world productivity in the field of minimally invasive spine surgery (MISS) research and to provide a general picture for surgeons and researchers. SUMMARY OF BACKGROUND DATA: Significant growth has been observed in the field of MISS research in recent years. However, bibliometric studies concerning the quantity and quality of articles published in MISS journals are scarce. METHODS: All the data concerning MISS in this study originate from the Web of Science (Thomson Reuters, New York, NY) without restrictions. All selected literates were evaluated in the following aspects: publication year, publication journals, author, times cited, Web of Science category, countries/territories. RESULTS: A total number of 2051 articles were published worldwide. The articles published during 2000 to 2015 are more than 11.28 times when compared to those published before 2000. The United States published the largest number of articles (855/2051, 41.7%), followed by Germany (245/2051, 11.9%), South Korea (160/2051, 7.8%), China (147/2051, 7.2%), and Japan (108/2051, 5.2%) and had the highest total citations (16,626). Additionally, the United States had the highest average citations per article (12.14), followed by Japan (11.98), Germany (11.19), South Korea (11.04), and China (10.95). High-income countries published 98.73% of articles, upper-middle income countries published 0.24% of articles, and middle-income countries published 1.03% of articles. CONCLUSION: The time trend for the number of MISS articles showed a significant increase over time with an average of 93.23 articles per year. The United States was the most productive country and had the highest average citations per article. Among related journals, Spine published the largest number of articles in MISS research and was the most popular one in the top five countries. LEVEL OF EVIDENCE: 5. PMID- 26679876 TI - Predicting Extended Length of Hospital Stay in an Adult Spinal Deformity Surgical Population. AB - STUDY DESIGN: A retrospective review of a prospective multicenter database. OBJECTIVE: The aim of this study was to identify variables associated with extended length of stay (ExtLOS) and this impact on health-related quality of life (HRQoL) scores in adult spinal deformity (ASD) patients. SUMMARY OF BACKGROUND DATA: ASD surgery is complex and associated with complications including extLOS. Although variables contributing to extLOS have been considered, specific complications and pre-disposing factors among ASD surgical patients remain to be investigated. METHODS: INCLUSION CRITERIA: ASD surgical patients (age >18 years, scoliosis >=20 degrees , sagittal vertical axis >=5 cm, pelvic tilt >=25 degrees , and/or thoracic kyphosis >60 degrees ) with complete demographic, radiographic, and HRQoL data at baseline, 6 weeks, and 2 years postoperative. ExtLOS was based on 75th percentile (>=9 days). Univariate and multivariate analyses identified predictors and evaluated effects on outcomes. Repeated-measures mixed models analyzed impact of ExtLOS on HRQoL [Oswestry Disability Index; Short Form-36 physical component summary/mental component summary; SRS22r Activity (AC), Pain (P), Appearance (AP), Satisfaction (S), Mental (M) and Total (T)]. RESULTS: Three hundred eighty patients met inclusion criteria: 105 (27.6%) had extLOS (>=9 days) and 275 (72.4%) did not. Average LOS was 8 days (range: 1-30 days). Age [odds ratio (OR) 1.04], no. of levels fused (OR 1.12), no. of infections (OR 2.29), no. of neurologic complications (OR 2.51), Charlson Comorbidity Index Score (CCI) predicted ExtLOS (OR 3.92), and no. of intraop complications predicted ExtLOS (OR 3.56). ExtLOS patients had more intracardiopulmonary (pleural effusion: 1.9% vs. 0%) and operative complications (dural tear: 13.3% vs. 5.1%; excessive blood loss: 18% vs. 5.8%) (P < 0.022). At 2 years, both groups of patients experienced an overall improvement in all HRQoL scores (P < 0.001). ExtLOS patients had significantly less overall improvement in all HRQoLs (P < 0.01) except for MCS (P = 0.17) and SRS M (P = 0.08). CONCLUSION: Extended LOS of ASD patients is affected by comorbidities (higher CCI) and number of intraoperative, but not peri-operative, complications. All patients improved overall in HRQoL scores, but extended LOS patients improved less overall at 2 years in comparison. LEVEL OF EVIDENCE: 3. PMID- 26679878 TI - Point of View. PMID- 26679877 TI - Effects of a Commercial Insurance Policy Restriction on Lumbar Fusion in North Carolina and the Implications for National Adoption. AB - STUDY DESIGN: An analysis of the State Inpatient Database of North Carolina, 2005 to 2012, and the Nationwide Inpatient Sample, including all inpatient lumbar fusion admissions from nonfederal hospitals. OBJECTIVE: The aim of the study was to examine the influence of a major commercial policy change that restricted lumbar fusion for certain indications and to forecast the potential impact if the policy were adopted nationally. SUMMARY OF BACKGROUND DATA: Few studies have examined the effects of recent changes in commercial coverage policies that restrict the use of lumbar fusion. METHODS: We included adults undergoing elective lumbar fusion or re-fusion operations in North Carolina. We aggregated data into a monthly time series to report changes in the rates and volume of lumbar fusion operations for disc herniation or degeneration, spinal stenosis, spondylolisthesis, or revision fusions. Time series regression models were used to test for significant changes in the use of fusion operation following a major commercial coverage policy change initiated on January 1, 2011. RESULTS: There was a substantial decline in the use of lumbar fusion for disc herniation or degeneration following the policy change on January 1, 2011. Overall rates of elective lumbar fusion operations in North Carolina (per 100,000 residents) increased from 103.2 in 2005 to 120.4 in 2009, before declining to 101.9 by 2012. The population rate (per 100,000 residents) of fusion among those under age 65 increased from 89.5 in 2005 to 101.2 in 2009, followed by a sharp decline to 76.8 by 2012. There was no acceleration in the already increasing rate of fusion for spinal stenosis, spondylolisthesis, or revision procedures, but there was a coincident increase in decompression without fusion. CONCLUSION: This commercial insurance policy change had its intended effect of reducing fusion operations for indications with less evidence of effectiveness without changing rates for other indications or resulting in an overall reduction in spine surgery. Nevertheless, broader adoption of the policy could significantly reduce the national rates of fusion operations and associated costs. LEVEL OF EVIDENCE: 3. PMID- 26679879 TI - Cervical Spine Movement and Ease of Intubation Using Truview or McCoy Laryngoscope in Difficult Intubation. AB - STUDY DESIGN: Prospective, observational, analytical, randomized control trial. OBJECTIVE: To compare cervical spine movement for best laryngoscopic view and ease of intubation using Truview or McCoy laryngoscope in anticipated difficult intubation. SUMMARY OF BACKGROUND DATA: The addition of modified laryngoscope blade to the anesthesiologist's armamentarium adds flexibility and improves the skill of the anesthetist, which benefits the patients. METHODS: One hundred patients of American Society of Anesthesiologists status I and II with predicted difficult intubation score >=5 were divided into two groups: Group A (n = 50): intubation done with McCoy laryngoscope and Group B (n = 50): intubation done with Truview laryngoscope and compared for the ease of intubation using intubation difficulty scale (IDS), cervical spine movement, and hemodynamic alterations. RESULTS: The total IDS determining the ease of tracheal intubation was better in Group B than Group A. On comparing the variables of IDS score, there was no difference between the two groups except 14 (28%) patients in Group A required application of external laryngeal pressure, whereas only five (10%) patients had this difficulty in Group B. It was seen that craniocervical extension was significantly less (2.5 times) in Group B as compared to Group A. CONCLUSION: In anticipated difficult intubation, Truview improves the laryngeal view, causes less movement at cervical spine, which could be more helpful in patients with restricted neck mobility, and has lesser complications. LEVEL OF EVIDENCE: 2. PMID- 26679880 TI - MRI-Guided Stereotactic System for Delivery of Intraspinal Microstimulation. AB - STUDY DESIGN: Laboratory/animal-based proof of principle study. OBJECTIVE: To validate the accuracy of a magnetic resonance imaging (MRI)-guided stereotactic system for intraspinal electrode targeting and demonstrate the feasibility of such a system for controlling implantation of intraspinal electrodes. SUMMARY OF BACKGROUND DATA: Intraspinal microstimulation (ISMS) is an emerging preclinical therapy, which has shown promise for the restoration of motor function following spinal cord injury. However, targeting inaccuracy associated with existing electrode implantation techniques remains a major barrier preventing clinical translation of ISMS. METHODS: System accuracy was evaluated using a test phantom comprised of nine target locations. Targeting accuracy was determined by calculating the root mean square error between MRI-generated coordinates and actual frame coordinates required to reach the target positions. System performance was further validated in an anesthetized pig model by performing MRI guided intraspinal electrode implantation and stimulation followed by computed tomography of electrode location. Finally, system compatibility with a commercially available microelectrode array was demonstrated by implanting the array and applying a selection of stimulation amplitudes that evoked hind limb responses. RESULTS: The root mean square error between actual frame coordinates and software coordinates, both acquired using the test phantom, was 1.09 +/- 0.20 mm. Postoperative computed tomography in the anesthetized pig confirmed spatially accurate electrode placement relative to preoperative MRI. Additionally, MRI guided delivery of a microwire electrode followed by ISMS evoked repeatable electromyography responses in the biceps femoris muscle. Finally, delivery of a microelectrode array produced repeatable and graded hind limb evoked movements. CONCLUSION: We present a novel frame-based stereotactic system for targeting and delivery of intraspinal instrumentation. This system utilizes MRI guidance to account for variations in anatomy between subjects, thereby improving upon existing ISMS electrode implantation techniques. LEVEL OF EVIDENCE: N/A. PMID- 26679881 TI - Differences in the Surgical Treatment of Lower Back Pain Among Spine Surgeons in the United States. AB - STUDY DESIGN: Electronic survey. OBJECTIVE: To identify the surgical treatment patterns for low back pain (LBP), among U.S. spine surgeons. Specifically determine (1) differences in surgical treatment responses based on various demographic variables; (2) probability of disagreement based on surgeon subgroups. SUMMARY OF BACKGROUND DATA: Multiple surgical and nonsurgical treatments exist for LBP. Without strong evidence or clear guidelines for the indications and optimal treatments, there is substantial variability in surgical treatments used. METHODS: A total of 445 U.S. spine surgeons completed a survey of clinical and radiographic case scenarios on patients with mechanical LBP, no leg pain, and concordant discograms. Surgical treatment options included no surgery, anterior lumbar interbody fusion (ALIF), posterolateral fusion with pedicle screws, transforaminal/posterior lumbar interbody fusion (TLIF/PLIF), etc. Statistical significance was set at 0.01 to account for multiple comparisons. RESULTS: There was substantial clinical equipoise (~75% disagreement) among surgeons on the approach to treat patients with LBP. Disagreement was highest in the southwest and lowest in the Midwest (82% vs. 69%, respectively); there was significantly lower disagreement among those in academic practices versus those in private/hybrid practices (56% vs.79%, respectively). Those in academic practices had approximately four times greater odds of choosing no surgery as compared to those in hybrid and private practices, who were more likely to choose ALIF or PLIF/TLIF. Those with fellowship training had approximately two times greater odds of selecting no surgery and four times greater odds of selecting ALIF as compared to those without fellowship training who were more likely to select TLIF/PLIF. CONCLUSION: Significant differences exist among U.S. spine surgeons in the treatment of LBP. These differences stem from geographical location of the practice, specialty, practice type, and fellowship training. Recognizing the substantial variability underlies the importance of additional studies aimed at identifying the proper indications and most cost-effective treatments for LBP. LEVEL OF EVIDENCE: 3. PMID- 26679882 TI - DISC (Degenerate-disc Infection Study With Contaminant Control): Pilot Study of Australian Cohort of Patients Without the Contaminant Control. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate if degenerative disc-related back or neck pain and/or radicular symptoms are caused by infection with low virulent bacterial organisms. SUMMARY OF BACKGROUND DATA: The potential relationship between disc infection and disc degeneration-related symptoms remains controversial, with contradictory evidence available in the literature. Several studies have demonstrated the presence of infected extruded nucleus tissue from first-time disc herniation, implicating the role of disc microbial infection in disc degeneration. The current study is a pilot study evaluating if high infection rates are prevalent in the Australian degenerate disc cohort. METHODS: Institutional ethics approval was obtained (HREC 13/218). The pilot project was a single spine center prospective cohort of patients undergoing spine surgery for degenerate disc disease. In each case, disc material was obtained and prolonged aerobic and anaerobic cultures performed as per methods used by Stirling et al. RESULTS: To date, a total of 168 patients have been enrolled, with male: female = 1:1. Surgical caseload includes 17.9% anterior cervical fusion, 35.0% anterior lumbar fusion, 40.7% lumbar discectomy, and 5.7% posterior lumbar fusions; 34.1% patients presented with neck pain, 31.6% with arm pain, 59.3% with leg pain, and 64.2% with back pain, and 20.2% of the patients received transforaminal or epidural or facet joint injections prior to surgery. In this pilot study, 19.6% were culture positive, with P. acnes predominant in 50%. Disc only cultures were positive in 27.8% of lumbar cases and 18.5% of cervical cases, with predominant organisms being P. acnes. CONCLUSION: Similar to the infection rates from previous studies, this Australian cohort had 19.6% infection rates when disc-only cultures are performed. P. acnes is the predominant organism followed by Streptococcus sp. It is imperative to perform contaminant controls as such high infection with skin bugs is a significant finding. LEVEL OF EVIDENCE: 4. PMID- 26679883 TI - Poor Radiological and Good Functional Long-term Outcome of Surgically Treated Scheuermann Patients. AB - STUDY DESIGN: Cohort study. OBJECTIVE: To analyze long-term clinical and radiological outcomes of surgically treated Scheuermann patients. SUMMARY OF BACKGROUND DATA: Long-term clinical and radiological outcomes of surgery for Scheuermann kyphosis are unknown. A single-center cohort of 33 consecutive, surgically treated (between 1991 and 1998) Scheuermann patients was studied. METHODS: Clinical and radiological data of 29 surgically treated Scheuermann patients were collected (posterior approach n = 13; combined anterior-posterior procedure n = 16), after a mean follow-up of 18 years. Oswestry Disability Index (ODI) scores were measured preoperatively (PRE) and twice postoperatively: 2 to 8 years postoperative (FU 1) and 14 to 21 years postoperative (FU 2). Visual Analog Score pain, Short Form-36 (SF-36), and EQ-5d scores were recorded at FU 2 only. Radiographs were analyzed for correction, distal and proximal junctional kyphosis, and implant failures. RESULTS: Mean preoperative kyphosis of the corrected levels was 76 degrees (range 60 degrees -105 degrees ) and decreased to a Cobb of 58 degrees (range 30 degrees -105 degrees ) at FU 2. Median Visual Analog Score was 2.5 points (range 0-8) and median ODI score was 12 (range 0-62) at FU 2. The ODI score at FU 1 was significantly better as compared to PRE (P < 0.001) and FU 2 (P < 0.001). Also, anterior-posterior treated group had a significantly better ODI score as compared to the posterior-only group (P = 0.023). EQ-5d scores on mobility, usual activities, and pain/discomfort were worse compared to an age-matched population control group; however, SF-36 outcome scores were comparable.Proximal junctional kyphosis was present in 53% of patients, distal junctional kyphosis did not occur, and implant failure/removal had occurred in 69% of patients. Radiological complications do not relate with the ODI, EQ-5d, and SF-36 and 72% of the patients were satisfied. CONCLUSION: Radiological results of this cohort were disappointing but did not relate to clinical outcome scores. Even lumbar pain could not prevent a high patient satisfaction and quality of life. Patients treated with a combined anterior posterior approach tended to perform better. LEVEL OF EVIDENCE: 3. PMID- 26679884 TI - TO THE EDITOR. PMID- 26679885 TI - TO THE EDITOR. PMID- 26679886 TI - Developing a Reliable Core Stability Assessment Battery for Patients with Nonspecific Low Back Pain. AB - STUDY DESIGN: Test-retest design. OBJECTIVE: The objective was to examine the intrarater (test-retest) reliability of the core stability related tests and to develop a reliable core stability assessment battery. SUMMARY OF BACKGROUND DATA: Studies suggest that core stability exercises may improve function and decrease pain in patients with nonspecific low back pain (LBP). Reliable clinical tests are required to implement adequate rehabilitation and to evaluate results of these interventions. METHODS: The study had a test-retest design. Thirty-three different tests that might relate to core stability were identified with their mostly used protocols. Five different components of core stability including endurance, flexibility, strength, functional performance, and motor control were assessed in 38 patients with nonspecific LBP. The same testing procedure was performed again after 48 to 72 hours. Intraclass correlation coefficients (ICCs), standard error of measurement, and minimal detectable change were calculated to assess the intrarater reliability. RESULTS: The intrarater reliability of the tests ranged from little to very high (ICC = 0.08-0.98). Partial curl-up (ICC = 0.90), lateral bridge (ICC = 0.95-0.96), trunk flexor endurance (ICC = 0.97), sit and reach (ICC = 0.98), single-legged hop (ICC = 0.98-0.97), lateral step-down (ICC = 0.93-0.92), eyes open right and left leg unilateral stance (ICC = 0.97 and 0.91) tests had the highest intrarater reliability for each core stability component. CONCLUSION: The results indicated that the partial curl-up test (strength), side bridge and trunk flexor tests (endurance), sit-and-reach test (flexibility), single-legged hop, and lateral step-down (functional), unilateral stance test with eyes open (motor control) had very high intrarater reliability. A core stability assessment battery involving these tests can be used in patients with nonspecific LBP to assess all components of core stability. LEVEL OF EVIDENCE: 3. PMID- 26679887 TI - The Natural History of Scoliosis in Females With Rett Syndrome. AB - STUDY DESIGN: Population-based longitudinal observational study. OBJECTIVE: To describe the prevalence of scoliosis in Rett syndrome, structural characteristics and progression, taking into account the influences of age, genotype, and ambulatory status. SUMMARY OF BACKGROUND DATA: Scoliosis is the most common orthopedic comorbidity in Rett syndrome yet very little is known about its natural history and influencing factors such as age, genotype, and ambulatory status. METHODS: The infrastructure of the Australian Rett Syndrome Database was used to identify all cases with confirmed Rett syndrome in Australia and collect data on genotype and walking status. We identified radiological records and described the Cobb angle of each curve. Time to event analysis was used to estimate the median age of onset of scoliosis and the log-rank test to compare by mutation type. Latent class group analysis was used to identify groups for the trajectory of walking status over time and a multilevel linear model used to assess trajectories of scoliosis development by mutation type and walking status. We used a logistic regression model to estimate the probability of developing a scoliosis with a Cobb angle >60 degrees at 16 years in relation to Cobb angle and walking status at 10 years of age. RESULTS: The median age of scoliosis onset was 11 years with earliest onset in those with a p.Arg255 mutation or large deletion. Scoliosis was progressive for all mutation types except for those with the p.Arg306Cys mutation. Scoliosis progression was reduced when there was capacity to walk independently or with assistance. Cobb angle and walking ability at age 10 can be reliably used to identify those who will develop a very severe scoliosis by age 16. CONCLUSION: These data on prognosis of scoliosis inform clinical decision making about the likelihood of progression to very severe scoliosis and the need for surgical management. LEVEL OF EVIDENCE: 4. PMID- 26679888 TI - Binding to COMP Reduces the BMP2 Dose for Spinal Fusion in a Rat Model. AB - STUDY DESIGN: The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. OBJECTIVE: To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. SUMMARY OF BACKGROUND DATA: BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. METHODS: Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 MUg) was tested with or without "low-dose" rhBMP-2 (2 MUg), and the results were compared with the "low-dose" (2 MUg rhBMP-2) and "high-dose" (10 MUg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. RESULTS: Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. CONCLUSION: COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose related adverse effects, surgical costs, and improve clinical outcomes. LEVEL OF EVIDENCE: N/A. PMID- 26679889 TI - Radiological Features of Scoliosis in Chiari I Malformation Without Syringomyelia. AB - STUDY DESIGN: A retrospective radiographic analysis. OBJECTIVE: The aim of this study was to investigate the scoliosis curve patterns/features and magnetic resonance imaging (MRI) tonsillar ectopia characteristics in Chiari I malformation without syringomyelia (CMI-only). SUMMARY OF BACKGROUND DATA: The development of scoliosis associated with a CMI typically has been ascribed to the presence of syringomyelia. However, a subset of CMI patients with scoliosis may not have a concomitant syrinx. Scoliosis in these patients has been very poorly documented in the literature. METHODS: A retrospective study was conducted on patients with a scoliosis secondary to CMI-only. The curve direction, curve pattern/features, and side of the dominant tonsillar ectopia were recorded and assessed quantitatively. On the basis of the measurement results, associations between the scoliosis curve patterns/features and MRI tonsillar ectopia characteristics were analyzed. RESULTS: A total of 26 patients, consisting of seven males and 19 females with an average age of 15.4 years, were included in the current study. In 19 patients with asymmetrically displaced tonsils, the concordance between the dominant side of the asymmetrically displaced tonsils and curve direction was 78.9%. A statistically significant association was found between the dominant side of the tonsillar ectopia and the convex side of scoliosis according to Fisher exact test (P = 0.045). In addition, it was noted that there was a high incidence (52.9%) of atypical curve patterns in CMI-only patients. A significantly high incidence of atypical features with a superior shift of either the apical or the end vertebrae was found in 85.7% of thoracic curves and 40% of lumbar curves. CONCLUSION: Scoliosis associated with CMI-only was found to have atypical curve patterns in all cases, and the direction of scoliosis was highly consistent with the dominant side of asymmetrically tonsillar herniation. These findings should be considered as an argument in favor of a nonidiopathic etiology and lead to more evidence that simple tonsillar impaction can provide enough impetus to produce or exaggerate scoliotic curvature. LEVEL OF EVIDENCE: 3. PMID- 26679890 TI - The Effect of Local Intraoperative Steroid Administration on the Rate of Postoperative Dysphagia Following ACDF: A Study of 245,754 Patients. AB - STUDY DESIGN: A retrospective database analysis. OBJECTIVE: The aim of this study is to compare rates of postoperative dysphagia, length of stay, infection, and wound complications following short and long anterior cervical discectomy and fusion (ACDF) in patients who received local intraoperative steroids and those who did not. SUMMARY OF BACKGROUND DATA: Only one prior small institutional study has investigated the application of local steroids at the time of ACDF to decrease postoperative dysphagia. METHODS: A large administrative database was utilized to compare rates of postoperative dysphagia, length of stay, and infectious complications within 90 days in patients who received local steroid following short (1-2 level) and long (3 or more level) ACDF and control groups who did not. Nonobtainable information within the database included type of steroid, application technique, outcome data, and incidence of miscoding and noncoding by physicians. Odds ratios (ORs), 95% confidence intervals (95% CIs) and P values were then calculated using SPSS. RESULTS: The incidence of dysphagia was significantly lower (9.0% vs. 14.6%, P = 0.005) in patients who received local steroid in the long ACDF group (n = 322) than a control group who did not (n = 45,432). This was not observed (P = 0.198) in the short ACDF group who received steroid (n = 1770) compared with a control group who did not (n = 198,230). The mean difference in length of stay was 1 day less for patients who received local steroid in both the short and long ACDF groups (P < 0.0001). The combined rate of postoperative infection and wound complications was not significantly different between steroid and control groups (P = 0.717). CONCLUSION: This analysis of a large administrative database suggests that local intraoperative steroid is associated with a significantly reduced rate of postoperative dysphagia after long ACDF and reduced average length of stay following both long and short ACDF without any increase in the rate of postoperative infection or wound complication. LEVEL OF EVIDENCE: 3. PMID- 26679891 TI - Risk of Neurological Injuries in Spinal Deformity Surgery. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: Rate of neurological injuries is widely reported for spinal deformity surgery. However, few have included the influence of the subtypes and severity of the deformity, or anterior versus posterior corrections. The purpose of this study is to quantify these risks. SUMMARY OF BACKGROUND DATA: The risk of neurological injuries was examined in a single institution. Quantification of risk was made between operations, and for different subtypes of spinal deformity. METHODS: Prospectively entered neuromonitoring database between 2006 and 2012 was interrogated, including all deformity cases under 21 years of age. Tumor, fracture, infection, and revision cases were excluded. All major changes in monitoring ("red alerts") were identified and detailed examinations of the neuromonitoring records, clinical notes, and radiographs were made. Diagnosis, deformity severity, and operative details were recorded. RESULTS: Of 2291 deformity operations, there were 2068 scoliosis (1636 idiopathic, 204 neuromuscular, 216 syndromic, 12 others), 89 kyphosis, 54 growing rod procedures, and 80 operations for hemivertebra. Six hundred ninety-six anterior and 1363 posterior operations were performed for scoliosis (nine not recorded), and 38 anterior and 51 posterior kyphosis corrections. Sixty-seven "red alerts" were identified (62 posterior, five anterior). Average Cobb angle was 88 degrees . There were 14 transient and six permanent neurological injuries. One permanent injury was sustained during kyphosis correction and five during scoliosis correction. Common surgeon reactions after "red alerts" were surgical pause with anesthetic interventions (n = 39) and the Stagnara wake-up test (n = 22). Metalwork was partially removed in 20, revised in 12, and completely removed in nine. Thirteen procedures were abandoned. CONCLUSION: The overall risk of permanent neurological injury was 0.2%. The highest risk groups were posterior corrections for kyphosis, and scoliosis associated with a syndrome. Four percent of all posterior deformity corrections had "red alerts," and 0.3% resulted in permanent injuries compared with 0.6% "red alerts" and 0.3% permanent injuries for anterior surgery. The overall risk for idiopathic scoliosis was 0.06%. LEVEL OF EVIDENCE: 3. PMID- 26679892 TI - Anterior Cervical Retropharyngeal Debridement Combined With Occipital Cervical Fusion to Upper Cervical Tuberculosis. AB - STUDY DESIGN: A retrospective analysis of 11 cases. OBJECTIVE: The aim of the study was to evaluate the effectiveness of anterior cervical and retropharyngeal debridement combined with posterior occipital-cervical fusion in treatment of upper cervical spinal tuberculosis. SUMMARY OF BACKGROUND DATA: The anterior approach simply could not provide strong fixation whereas the posterior treatment could not clear up the lesions completely. The method combining anterior and posterior approaches to treat the upper cervical tuberculosis is advisable. METHODS: The clinical data of 11 patients with upper cervical tuberculosis who underwent an upper cervical operation in our hospital were retrospectively analyzed. All 11 patients underwent the surgery of anterior cervical and retropharyngeal approaches to debridement, and then, according to the different degrees of patient pedicle destruction and deformity, different occipitocervical approaches were used (either through pedicle screw or laminar screw fixation). After surgery, antituberculosis drugs were administered for 18 months. During the follow-up, neurological function, clinical symptoms, fusion, reducible degree, and complications were all evaluated and documented. RESULTS: Surgeries for 11 patients were performed successfully; anatomical reduction was achieved in nine cases, bony fusion was achieved in all 11 patients, and all cases with tuberculosis were clinically cured in the 18 months after the operation. The Japanese Orthopaedic Association score increased from 8.4 +/- 1.3 preoperative to 15.0 +/- 1.3 in the last follow-up (P < 0.05). The occipitocervical visual analog scale decreased from 6.7 +/- 0.6 preoperative to 0.6 +/- 0.6 at the last follow up (P < 0.05). No serious complications were documented during follow-up. CONCLUSION: The approach of anterior cervical and retropharyngeal debridement combined with posterior occipitocervical fusion has been proved to be an effective treatment of upper cervical tuberculosis, which plays an important role in removing the lesions, restoring stability, and anatomical reduction. LEVEL OF EVIDENCE: 4. PMID- 26679893 TI - Identification of Differential Genes Expression Profiles and Pathways of Bone Marrow Mesenchymal Stem Cells of Adolescent Idiopathic Scoliosis Patients by Microarray and Integrated Gene Network Analysis. AB - STUDY DESIGN: Microarray approach and integrated gene network analysis. OBJECTIVE: To explore the differential genetic expression profile, gene ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in bone marrow mesenchymal stem cells (BM-MSCs) of idiopathic scoliosis (AIS) and non-AIS controls. SUMMARY OF BACKGROUND DATA: The pathogenesis of adolescent AIS and the accompanying generalized osteopenia remain unclear. Our previous study suggested increased proliferation ability and decreased osteogenic differentiation ability of BM-MSCs of AIS. Therefore, we hypothesized that MSCs may play a significant role in the etiology and pathogenesis of AIS. METHODS: In this study, microarray analysis was used to identify differentially expressed genes (DEGs) of BM-MSCs from AIS patients compared with those from healthy individuals. Comprehensive bioinformatics analyses were then used to enrich datasets for gene ontology and pathway. Based on the gene signal transduction network analysis of DEGs contained in significant pathways, 24 potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. RESULTS: There are 1027 previously unrecognized DEGs in BM-MSCs from AIS patients. Pathway analysis revealed dysregulated mitogen-activated protein kinase (MAPK) signaling pathway, PI3K-Akt signaling pathway, calcium signaling pathway, peroxisome proliferator activated receptor (PPAR) signaling pathway, ubiquitin-mediated proteolysis, and Notch signaling pathway, all of which have been reported to play an important role in regulating the osteogenic or adipogenic differentiation of MSCs. Furthermore, gene signal transduction networks analysis indicated that mitogen activated protein kinase kinase 1 (MAP2K1), SMAD family member 3 (SMAD3), homeobox C6 (HOXC6), heat shock 70kDa protein 6 (HSPA6), general transcription factor IIi (GTF2I), CREB binding protein (CREBBP), phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2), and dual specificity phosphatase 2 (DUSP2) may play essential roles in AIS pathogenesis and accompanied osteopenia. CONCLUSION: This study reports the differential genes expression profiles of BM-MSCs from AIS patients and related potential pathways for the first time. These previously unrecognized genes and molecular pathways might play a significant role in not only the causal mechanism of osteopenia in AIS, but also the AIS initiation and development. The identification of these candidate genes provides novel insight into the underlying etiological mechanisms of AIS. LEVEL OF EVIDENCE: N/A. PMID- 26679894 TI - Pilates for Low Back Pain: Complete Republication of a Cochrane Review. AB - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the effects of the Pilates method for patients with nonspecific acute, subacute, or chronic low back pain. SUMMARY OF BACKGROUND DATA: The Pilates method is one of the most common forms of intervention based on exercise used for treating patients with low back pain. However, its effectiveness is not well established. METHODS: We conducted searches on CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, and SPORTDiscus up to March 2014. We included randomized controlled trials examining the effectiveness of Pilates in patients with acute, subacute, or chronic nonspecific low back pain. The outcomes evaluated were pain, disability, function, and global impression of recovery. Two independent reviewers screened for potentially eligible studies, assessed risk of bias, and extracted the data. We evaluated the overall quality of evidence using the GRADE approach and treatment effect sizes were described using mean differences and 95% confidence intervals. RESULTS: Searches retrieved 126 trials, of which 10 were included in the review (n = 510 participants). Seven studies were considered to have low risk of bias, and three were considered at high risk of bias. When compared to minimal intervention, Pilates reduces pain at short and intermediate term with low- to moderate-quality evidence and medium effect sizes. For disability, there is also a significant difference in favor to Pilates with low- to moderate-quality evidence and small effect size for short term and medium effect size for intermediate term compared with minimal intervention. It is unclear whether Pilates is better than other exercises for short-term pain, but there is low-quality evidence that Pilates reduces pain at intermediate term. For disability, there is moderate-quality evidence that there is no significant difference between Pilates and other exercises in either the short term or the intermediate term. CONCLUSION: There is low- to moderate quality evidence that Pilates is more effective than minimal intervention with most of the effect sizes being considered medium. However, there is no conclusive evidence that Pilates is superior to other forms of exercises. LEVEL OF EVIDENCE: 1. PMID- 26679895 TI - Factors related to prevalence, persistence, and incidence of depressive symptoms in mild cognitive impairment: vascular depression construct. AB - OBJECTIVE: Depression is prevalent among elders with cognitive impairment. Cerebral white matter hyperintensities (WMH) have consistently been implicated in late-life depression and in cognitive impairment. This study aims to clarify the factors related to prevalence, persistence, and new onset of depressive symptoms in subjects with mild cognitive impairment (MCI). METHODS: As part of a multicenter prospective study, the Clinical Research Center for Dementia of South Korea (CREDOS) Study, we enrolled 590 subjects diagnosed with MCI and with no prior history of depression. Depressive symptoms were assessed by the Korean version of the Geriatric Depression Scale short form (SGDS-K) at baseline and at follow-up visits. Brain magnetic resonance imaging was performed at baseline to quantify WMH using a visual rating scale. RESULTS: The baseline prevalence of clinically significant depressive symptoms (SGDS-K >=5) was 51.4%, and this feature was associated with younger age, lower educational achievement, and higher Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Persistence of depressive symptoms across the study period was significantly associated with baseline CDR-SB and depression scores. New onset of depression (SGDS-K >=8; incidence 15.7%) among subjects free of depressive symptoms (SGDS-K <5) at baseline was associated with severe deep subcortical, but not periventricular, WMH. CONCLUSIONS: In patients with MCI aged 50 years or older, depressive symptoms were highly prevalent. Cognitive status was closely related to both prevalence and persistence of depressive symptoms, while new onset of depression was associated with deep subcortical WMH severity in this MCI cohort. Our findings provide prospective evidence consistent with the vascular depression hypothesis. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26679897 TI - Quantifying the erosion effect on current carbon budget of European agricultural soils at high spatial resolution. AB - The idea of offsetting anthropogenic CO2 emissions by increasing global soil organic carbon (SOC), as recently proposed by French authorities ahead of COP21 in the 'four per mil' initiative, is notable. However, a high uncertainty still exits on land C balance components. In particular, the role of erosion in the global C cycle is not totally disentangled, leading to disagreement whether this process induces lands to be a source or sink of CO2. To investigate this issue, we coupled soil erosion into a biogeochemistry model, running at 1 km(2) resolution across the agricultural soils of the European Union (EU). Based on data-driven assumptions, the simulation took into account also soil deposition within grid cells and the potential C export to riverine systems, in a way to be conservative in a mass balance. We estimated that 143 of 187 Mha have C erosion rates <0.05 Mg C ha(-1) yr(-1), although some hot-spot areas showed eroded SOC >0.45 Mg C ha(-1) yr(-1). In comparison with a baseline without erosion, the model suggested an erosion-induced sink of atmospheric C consistent with previous empirical-based studies. Integrating all C fluxes for the EU agricultural soils, we estimated a net C loss or gain of -2.28 and +0.79 Tg yr(-1) of CO2 eq, respectively, depending on the value for the short-term enhancement of soil C mineralization due to soil disruption and displacement/transport with erosion. We concluded that erosion fluxes were in the same order of current carbon gains from improved management. Even if erosion could potentially induce a sink for atmospheric CO2, strong agricultural policies are needed to prevent or reduce soil erosion, in order to maintain soil health and productivity. PMID- 26679900 TI - Plans to consult on the docking of working dogs' tails in Scotland. PMID- 26679898 TI - Prion protein localizes at the ciliary base during neural and cardiovascular development, and its depletion affects alpha-tubulin post-translational modifications. AB - Although conversion of the cellular form of the prion protein (PrP(C)) into a misfolded isoform is the underlying cause of prion diseases, understanding PrP(C) physiological functions has remained challenging. PrP(C) depletion or overexpression alters the proliferation and differentiation properties of various types of stem and progenitor cells in vitro by unknown mechanisms. Such involvement remains uncertain in vivo in the absence of any drastic phenotype of mice lacking PrP(C). Here, we report PrP(C) enrichment at the base of the primary cilium in stem and progenitor cells from the central nervous system and cardiovascular system of developing mouse embryos. PrP(C) depletion in a neuroepithelial cell line dramatically altered key cilium-dependent processes, such as Sonic hedgehog signalling and alpha-tubulin post-translational modifications. These processes were also affected over a limited time window in PrP(C)-ablated embryos. Thus, our study reveals PrP(C) as a potential actor in the developmental regulation of microtubule dynamics and ciliary functions. PMID- 26679901 TI - Welsh Government seeks views on alternatives to the six-day standstill. PMID- 26679899 TI - Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change. AB - AIMS: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). METHODS AND RESULTS: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. CONCLUSIONS: TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer. PMID- 26679902 TI - Flood advice for animal owners and keepers. PMID- 26679903 TI - Mitigating the impact of flash flooding. PMID- 26679904 TI - OIE highlights the importance of animal production for humanity. PMID- 26679905 TI - Collaborating with CITES. PMID- 26679906 TI - Members sought for Vet Futures action group. PMID- 26679907 TI - Getting down to business at BCVA congress. PMID- 26679908 TI - First IVF puppies 'open the door' for the conservation of endangered canids. PMID- 26679909 TI - HPAI spreads in France. PMID- 26679910 TI - Speaking up for cats. PMID- 26679911 TI - EBVM: application in everyday practice. AB - Essential tools to help practitioners integrate evidence-based veterinary medicine (EBVM) into everyday practice were discussed recently at a 'skills day' organised by RCVS Knowledge. Kristy Ebanks reports. PMID- 26679912 TI - Fighting food waste, feeding the planet. AB - In October, Kasia Szymanska, a final-year veterinary student at University College Dublin, was invited to attend a conference organised by the European Commission on preventing food waste. Here, she reports on the meeting, and explains why she believes that vets have an important role to play in optimising food production and minimising waste. PMID- 26679913 TI - Whose animal is it anyway? AB - In today's world, there is easy access to new and exotic destinations, and many weird and wonderful species can be seen on television. But should these species be kept as pets, and whose job is it to tell people what pets they can and cannot keep? This was a topic discussed at the BVA Congress on November 19. Georgina Mills reports. PMID- 26679914 TI - Mycoplasma bovis mastitis and arthritis in a dairy heifer. AB - Mycoplasma bovis causing mastitis and arthritis in a dairy heifer. Nutritional myopathy in a three-month-old suckler calf. Acute fasciolosis in ewes in Ayrshire. Cardiomyopathy of unknown aetiology causing death of a three-year-old Suffolk ram. Spinal aspergillosis in a seven-week-old pheasant poult These are among matters discussed in the disease surveillance report for August from SAC Consulting: Veterinary Services (SAC C VS). PMID- 26679915 TI - Using natriuretic peptides to detect cardiac diseases in horses. PMID- 26679916 TI - Porcine epidemic diarrhoea: obligation to notify in England. PMID- 26679917 TI - Providing for behavioural health in general practice. PMID- 26679918 TI - One Welfare. PMID- 26679919 TI - Diagnosis and reporting of antifreeze poisoning. PMID- 26679920 TI - Three-dimensional anatomy. AB - After her final year studying veterinary medicine at the Royal Veterinary College (RVC) and before starting an internship, Vicky Simons took on the job of creating a life-size equine anatomical model 'anatohorse' (also known as Geoff). PMID- 26679921 TI - Second-year student diary. AB - Despite having lots to learn - and lots to organise for Christmas and her dad's retirement - Rosie Perrett recently enjoyed a weekend break with her friends from her previous degree course. PMID- 26679922 TI - Furan oxidation based cross-linking: a new approach for the study and targeting of nucleic acid and protein interactions. AB - Furan mediated nucleic acid cross-linking, initially developed for DNA interstrand duplex cross-linking, has matured into a versatile tool for the study of protein and nucleic acid interactions, ready to face its applications. The methodology was initially developed for easy and clean chemical generation of DNA interstrand cross-linked duplexes, but has been further expanded for use with other probes, targets and triggers, now allowing mild biologically significant cross-linking with potential therapeutic benefit. It was shown that the methodology could be repurposed for RNA interstrand cross-linking, which is very relevant in today's antisense approaches or miRNA target identification endeavors. This further illustrates the furan oxidation method's generality and mildness, especially when using red light for oxidation. A complementary antigene approach has been explored through duplex targeting with furan modified triplex forming oligonucleotides (TFOs) and DNA binding proteins. Also targeting of peptides and proteins by furan-modified DNA and peptides has been explored. Thorough methodology examination exploring variable reaction conditions in combination with a series of different furan-modified building blocks and application of different activation signals resulted in a detailed understanding of the mechanisms involved and factors influencing the yield and selectivity of the reaction. In order to draw the bigger picture of the scope and limitations of furan-oxidation cross-linking, we here provide a unique side by side comparison and discussion of our published data, supplemented with unpublished results, providing a clear performance report of the currently established furan toolbox and its application potential in various biomacromolecular complexes. PMID- 26679923 TI - Detection of intestinal parasites by use of the cuvette-based automated microscopy analyser sediMAX((r)). AB - Microscopy is the reference method for intestinal parasite identification. The cuvette-based automated microscopy analyser, sediMAX 1, provides 15 digital images of each sediment sample. In this study, we have evaluated this fully automated instrument for detection of enteric parasites, helminths and protozoa. A total of 700 consecutively preserved samples consisting of 60 positive samples (50 protozoa, ten helminths) and 640 negative samples were analysed. Operators were blinded to each others' results. Samples were randomized and were tested both by manual microscopy and sediMAX 1 for parasite recognition. The sediMAX 1 analysis was conducted using a dilution of faecal samples, allowing determination of morphology. The data obtained using sediMAX 1 showed a specificity of 100% and a sensitivity of 100%. Some species of helminths, such as Enterobius vermicularis, Strongyloides stercolaris, the Ancylostoma duodenale/Necator americanus complex, and schistosomes were not considered in this work, because they are rare in stool specimens, are not easily detectable with microscopy analysis, and require specific recovery techniques. This study demonstrated for the first time that sediMAX 1 can be an aid in enteric parasite identification. PMID- 26679924 TI - Escherichia coli and urinary tract infections: the role of poultry-meat. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common cause of community-acquired and hospital-acquired extraintestinal infections. The hypothesis that human ExPEC may have a food animal reservoir has been a topic of investigation by multiple groups around the world. Experimental studies showing the shared pathogenic potential of human ExPEC and avian pathogenic E. coli suggest that these extraintestinal E. coli may be derived from the same bacterial lineages or share common evolutionary roots. The consistent observation of specific human ExPEC lineages in poultry or poultry products, and rarely in other meat commodities, supports the hypothesis that there may be a poultry reservoir for human ExPEC. The time lag between human ExPEC acquisition (in the intestine) and infection is the fundamental challenge facing studies attempting to attribute ExPEC transmission to poultry or other environmental sources. Even whole genome sequencing efforts to address attribution will struggle with defining meaningful genetic relationships outside of a discrete food-borne outbreak setting. However, if even a fraction of all human ExPEC infections, especially antimicrobial resistant ExPEC infections, is attributable to the introduction of multidrug resistant ExPEC lineages through contaminated food product(s), the relevance to public health, food animal production and food safety will be significant. PMID- 26679925 TI - Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings. AB - BACKGROUND: Data on structural brain alterations in patients with attention deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. METHODS: We performed voxel based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. RESULTS: Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. LIMITATIONS: Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. CONCLUSION: Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID- 26679927 TI - Network Structure and Biased Variance Estimation in Respondent Driven Sampling. AB - This paper explores bias in the estimation of sampling variance in Respondent Driven Sampling (RDS). Prior methodological work on RDS has focused on its problematic assumptions and the biases and inefficiencies of its estimators of the population mean. Nonetheless, researchers have given only slight attention to the topic of estimating sampling variance in RDS, despite the importance of variance estimation for the construction of confidence intervals and hypothesis tests. In this paper, we show that the estimators of RDS sampling variance rely on a critical assumption that the network is First Order Markov (FOM) with respect to the dependent variable of interest. We demonstrate, through intuitive examples, mathematical generalizations, and computational experiments that current RDS variance estimators will always underestimate the population sampling variance of RDS in empirical networks that do not conform to the FOM assumption. Analysis of 215 observed university and school networks from Facebook and Add Health indicates that the FOM assumption is violated in every empirical network we analyze, and that these violations lead to substantially biased RDS estimators of sampling variance. We propose and test two alternative variance estimators that show some promise for reducing biases, but which also illustrate the limits of estimating sampling variance with only partial information on the underlying population social network. PMID- 26679926 TI - A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males. AB - BACKGROUND: The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2(-/-) mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning. METHODS: Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2(-/-) mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608). RESULTS: The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct "modules," or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001). LIMITATIONS: It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2(-/-) mice by perturbed mesolimbic dopamine signalling or by the loss of Rasgrf2 function in the NAcc. CONCLUSION: Taken together, our findings indicate that the accumbal M5 module, initially identified as being dysregulated in male Rasgrf2(-/-) mice, is also relevant for human alcohol-related phenotypes potentially through the modulation of reinforcement mechanisms in the NAcc. We therefore propose that the genes comprising this module represent important candidates for further elucidation within the context of alcohol-related phenotypes. PMID- 26679928 TI - Structural mechanical properties of radiation-sterilized human Bone-Tendon-Bone grafts preserved by different methods. AB - To avoid the risk of infectious disease transmission from donor to recipient, allografts should be terminally sterilized. In the previous paper (Kaminski et al. in Cell Tissue Bank 10:215-219, 2009) we presented the effect of various methods of preservation (deep fresh freezing, glycerolization, lyophilization), followed by irradiation with different doses of electron beam (EB), on material (intrinsic) mechanical properties of human patellar tendons cut out as for anterior cruciate ligament reconstruction, obtained in failure tensile test. As structural mechanical properties are equally important to predict the behaviour of the graft as a whole functional unit, the purpose of the present paper was to show the results for failure load and elongation, obtained in the same experiment. Paired Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. They were preserved by deep freezing, glycerolization or lyophilization and subsequently EB irradiated with the doses of 25, 35, 50 or 100 kGy (fresh-frozen grafts) or a single dose of 35 kGy (glycerolized and lyophilized grafts). Each experimental (irradiated) group was provided with control (non-irradiated), donor-matched group. The specimens from all groups were subjected to mechanical failure tensile test with the use of Instron system in order to measure their structural properties (failure load and elongation). All lyophilized grafts were rehydrated before mechanical testing. In our study we did not observe significant deterioration of structural mechanical properties of BTB grafts processed by fresh-freezing and then terminal sterilized with growing doses of EB up to 100 kGy. In contrast, BTB grafts processed by glycerolization or lyophilization and irradiated with 35 kGy showed significant decrease of failure load. Obtained results suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not exclude their clinical application. However, biomechanical investigations constitute only the first step to evaluate the potential clinical usefulness of such allografts and further extensive in vivo studies are needed. PMID- 26679929 TI - Isolation and proliferation of umbilical cord tissue derived mesenchymal stem cells for clinical applications. AB - Umbilical cord (UC) is a rich source of rapidly proliferating mesenchymal stem cells (MSCs) that are easily cultured on a large-scale. Clinical applications of UC-MSCs include graft-versus-host disease, and diabetes mellitus types 1 and 2. UC-MSCs should be isolated and proliferated according to good manufacturing practice (GMP) with animal component-free medium, quality assurance, and quality control for their use in clinical applications. This study developed a GMP standard protocol for UC-MSC isolation and culture. UC blood and UC were collected from the same donors. Blood vasculature was removed from UC. UC blood was used as a source of activated platelet rich plasma (aPRP). Small fragments (1 2 mm(2)) of UC membrane and Wharton's jelly were cut and cultured in DMEM/F12 medium containing 1 % antibiotic-antimycotic, aPRP (2.5, 5, 7.5 and 10 %) at 37 degrees C in 5 % CO2. The MSC properties of UC-MSCs at passage 5 such as osteoblast, chondroblast and adipocyte differentiation, and markers including CD13, CD14, CD29, CD34, CD44, CD45, CD73, CD90, CD105, and HLA-DR were confirmed. UC-MSCs also were analyzed for karyotype, expression of tumorigenesis related genes, cell cycle, doubling time as well as in vivo tumor formation in NOD/SCID mice. Control cells consisted of UC-MSCs cultured in DMEM/F12 plus 1 % antibiotic antimycotic, and 10 % fetal bovine serum (FBS). All UC-MSC (n = 30) samples were successfully cultured in medium containing 7.5 and 10 % aPRP, 92 % of samples grew in 5.0 % aPRP, 86 % of samples in 2.5 % aPRP, and 72 % grew in 10 % FBS. UC MSCs in these four groups exhibited similar marker profiles. Moreover, the proliferation rates in medium with PRP, especially 7.5 and 10 %, were significantly quicker compared with 2.5 and 5 % aPRP or 10 % FBS. These cells maintained a normal karyotype for 15 sub-cultures, and differentiated into osteoblasts, chondroblasts, and adipocytes. The analysis of pluripotent cell markers showed UC-MSCs maintained the expression of the oncogenes Nanog and Oct4 after long term culture but failed to transfer tumors in NOD/SCID mice. Replacing FBS with aPRP in the culture medium for UC tissues allowed the successful isolation of UC-MSCs that satisfy the minimum standards for clinical applications. PMID- 26679930 TI - Isolation, characterisation and comparative analysis of human umbilical cord vein perivascular cells and cord blood mesenchymal stem cells. AB - Perivascular cells are known to be ancestors of mesenchymal stem cells (MSCs) and can be obtained from heart, skin, bone marrow, eye, placenta and umbilical cord (UC). However detailed characterization of perivascular cells around the human UC vein and comparative analysis of them with MSCs haven't been done yet. In this study, our aim is to isolate perivascular cells from human UC vein and characterize them versus UC blood MSCs (UCB-MSCs). For this purpose, perivascular cells around the UC vein were isolated enzymatically and then purified with magnetic activated cell sorting (MACS) method using CD146 Microbead Kit respectively. MSCs were isolated from UCB by Ficoll density gradient solution. Perivascular cells and UCB-MSCs were characterized by osteogenic and adipogenic differentiation procedures, flow cytometric analysis [CD146, CD105, CD31, CD34, CD45 and alpha-smooth muscle actin (alpha-SMA)], and immunofluorescent staining (MAP1B and Tenascin C). Alizarin red and Oil red O staining results showed that perivascular cells and MSCs had osteogenic and adipogenic differentiation capacity. However, osteogenic differentiation capacity of perivascular cells were found to be less than UCB-MSCs. According to flow cytometric analysis, CD146 expression of perivascular cells were appeared to be 4.8-fold higher than UCB MSCs. Expression of alpha-SMA, MAP1B and Tenascin-C from perivascular cells was determined by flow cytometry analysis and immunfluorescent staining. The results appear to support the fact that perivascular cells are the ancestors of MSCs in vascular area. They may be used as alternative cells to MSCs in the field of vascular tissue engineering. PMID- 26679931 TI - Human metabolism of alpha-pinene and metabolite kinetics after oral administration. AB - We studied the human in vivo metabolism and the elimination kinetics of alpha pinene (alphaPN), a natural monoterpene which commonly occurs in the environment. Four volunteers were exposed to a single oral dose of 10 mg alphaPN. Each subject provided one pre-exposure and subsequently all post-exposure urine samples up to 24 h after administration. Additionally, blood samples were drawn hourly from two volunteers for 5 h. The analysis of the parent compound in blood was performed by a headspace GC-MS procedure, whereas the proposed alphaPN metabolites myrtenol (MYR) and cis- and trans-verbenol (cVER; tVER) were quantified in blood and urine using GC-PCI-MS/MS. Unknown metabolites were investigated using GC-PCI-MS full scan analyses. The urinary concentration of the metabolites reached their maxima 1.6 h after exposure. Afterwards, they declined to the pre-exposure levels within the 24-h observation period with elimination half-lives of 1.5 h (MYR) and 1.6 h (cVER and tVER). The total eliminated amounts corresponded to 1.5 % (MYR), 5.6 % (cVER), and 4.1 % (tVER) of the orally applied dose. The GC-PCI-MS full-scan analyses identified three novel metabolites, of which one conforms to myrtenic acid (MYRA). A re-analysis of MYRA in urine showed maximum elimination 1.6 h after alphaPN ingestion, an elimination half-life of 1.4 h, and a share of the oral dose of 6.7 %. The study revealed that the human in vivo metabolism of alphaPN proceeds fast and elimination of metabolites takes places rapidly. The metabolism of alphaPN is dominated by extensive oxidation reactions at the methyl side-chains yielding in carboxylic acid structures as well as by allylic oxidation of the cyclohexenyl backbone, whereas predicted products of a double bond oxidation were not detected. PMID- 26679932 TI - High-grade glioma in children and adolescents: a single-center experience. AB - PURPOSE: The aim of this study was to report the outcome in children with high grade astrocytoma outside the brain stem and spinal cord that were treated at a single center. MATERIALS AND METHODS: The study included 26 patients with anaplastic astrocytoma and 37 patients with glioblastoma; all patients were aged <=18 years. At initial diagnosis, 18 of the patients with glioblastoma received only temozolomide (TMZ), 14 received other chemotherapies, and 5 did not receive any chemotherapy. Among the patients with anaplastic astrocytoma, 9 received TMZ, 9 received other chemotherapy regimens, and 8 patients did not receive any chemotherapy. The median radiotherapy dose in all patients was 60 Gy. RESULTS: Median age of the patients was 12.5 years. Median overall survival was 20 months and mean progression-free survival was 4.7-11.3 months (median: 8 months) in all patients. Patients with a Karnofsky performance score (KPS) >=70 had median overall survival of 32 months, versus 7 months in those with a KPS < 70. Patients aged <15 years had median survival of 38 months, versus 16 months in those aged 15-18 years. Patients with anaplastic astrocytoma that received TMZ, other chemotherapy regimens, and no chemotherapy had median survival of 21 months, 132 months, and 11 months, respectively. Patients with glioblastoma that received TMZ, other chemotherapy regimens, and no chemotherapy had median survival of 32 months, 12 months, and 8 months, respectively. CONCLUSION: In the present study, patients with anaplastic astrocytoma treated with chemotherapy protocols other than TMZ had the longest OS; however, in the glioblastoma group, OS was 32 months in those treated with standard TMZ and 12 months in those treated with other protocols (P = 0.493). Although TMZ is less toxic than PCV, it was not shown to be superior. PMID- 26679933 TI - Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals. AB - It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1-5, 6-10, 11-15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064 4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117-2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1-5), DGF(6-10), and DGF(11-15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0+/-24.6 vs. 55.8+/-22.2 vs. 53.8+/ 24.1 vs. 53.0+/-27.2 vs. 36.8+/-27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270-6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055-8.193, p<0.001), and death (OR 3.065, CI95% 1.536-6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year. PMID- 26679934 TI - Is secondhand smoke associated with stress in smokers and non-smokers? AB - BACKGROUND: Secondhand Smoking (SHS) has been suggested as a major health problem in the world and is known to cause various negative health effects that have in turn caused the deaths of almost 600,000 people per year. Evidence has suggested that SHS may have an effect on health problems and such findings have influenced the implementation of smoking-free areas. However, few studies have investigated the effects of SHS on stress which is considered major risk factor for mental health. Thus, the purpose of our study was to investigate the association between exposure to SHS and stress. METHODS: We performed a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (2007-2012). In our study, a total of 33,728 participants were included to evaluate the association between SHS exposure and stress based on smoking status. Association between SHS exposure and stress was examined using logistic regression models. RESULTS: A total of 12,441 participants (42.9 %) were exposed to SHS in the workplace or at home. In our study, exposure to SHS was significantly associated with higher stress compared to non-exposure, regardless of smoking status (smoker odds ratio [OR]: 1.22; ex-smoker OR: 1.25; never-smoker OR: 1.42). Our results showed that the effect of SHS on stress was greater when exposure took place both at home and in the workplace in smokers and never-smokers. CONCLUSIONS: Exposure to SHS in the workplace and at home is considered to be a risk factor for high stress in both smokers and never-smoker. Therefore, strict regulations banning smoke which can smoking ban reduce SHS exposure are recommended in order to improve the populations' health. PMID- 26679935 TI - Effects of Epicardial and Endocardial Cardiac Resynchronization Therapy on Coronary Flow: Insights From Wave Intensity Analysis. AB - BACKGROUND: The increase in global coronary flow seen with conventional biventricular pacing is mediated by an increase in the dominant backward expansion wave (BEW). Little is known about the determinants of flow in the left sided epicardial coronary arteries beyond this or the effect of endocardial pacing stimulation on coronary physiology. METHODS AND RESULTS: Eleven patients with a chronically implanted biventricular pacemaker underwent an acute hemodynamic and electrophysiological study. Five of 11 patients also took part in a left ventricular endocardial pacing protocol at the same time. Conventional biventricular pacing, delivered epicardially from the coronary sinus, resulted in a 9% increase in flow (average peak velocity) in the left anterior descending artery (LAD), mediated by a 13% increase in the area under the BEW (P=0.004). Endocardial pacing resulted in a 27% increase in LAD flow, mediated by a 112% increase in the area under the forward compression wave (FCW) and a 43% increase in the area under the BEW (P=0.048 and P=0.036, respectively). There were no significant changes in circumflex parameters. Conventional biventricular pacing resulted in homogenization of timing of coronary flow compared with baseline (mean difference in time to peak in the LAD versus circumflex artery: FCW 39 ms [baseline] versus 3 ms [conventional biventricular pacing], P=0.008; BEW 47 ms [baseline] versus 8 ms [conventional biventricular pacing], P=0.004). CONCLUSIONS: Epicardial and endocardial pacing result in increased coronary flow in the left anterior descending artery and homogenization of the timing of waves that determine flow in the LAD and the circumflex artery. The increase in both the FCW and the BEW with endocardial pacing may be the result of a more physiological activation pattern than that of epicardial pacing, which resulted in an increase of only the BEW. PMID- 26679936 TI - Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex. AB - OBJECTIVE: The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. METHOD: 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. RESULTS: Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. CONCLUSION: Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects. PMID- 26679937 TI - Characterization of Lung Fibroblasts More than Two Decades after Mustard Gas Exposure. AB - PURPOSE: In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas. METHODS: Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985-7 and compared with the fibroblasts of control subjects. RESULTS: Compared with controls, patients' fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation. CONCLUSIONS: These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components. PMID- 26679938 TI - Critical Appraisal of the Quality of Literature Evaluating Psychometric Properties of Arthritis Work Outcome Assessments: A Systematic Review. AB - OBJECTIVE: To systematically rate the evidence on the measurement properties of work functioning instruments for people with arthritis and other rheumatologic conditions. METHODS: A systematic review was conducted through a structured search to identify the quality of articles describing studies of assessment development and studies of their psychometric properties. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was used to appraise the included studies. Finally, an evidence synthesis was performed to combine findings. RESULTS: Nine arthritis-specific work outcome assessments were identified; 17 articles examining the psychometric properties of these instruments were identified and their quality was reviewed. Quality of studies was highly variable. The evidence synthesis showed that the Work Limitations Questionnaire had the strongest quality evidence of internal consistency and content validity (including structural validity and hypothesis testing), followed by the Work Instability Scale. None of the instruments had strong quality evidence of criterion validity or responsiveness. CONCLUSION: Considering the high variability and the low quality of the literature, we recommend that instrument developers integrate a full psychometric assessment of their instruments, including responsiveness and criterion validity, and consult guidelines (i.e., COSMIN) in reporting their findings. PMID- 26679940 TI - Qualitative Methods in Community-Based Participatory Research: Coming of Age. PMID- 26679939 TI - PPARgamma Agonist Ameliorates the Impaired Fluidity of the Myocardial Cell Membrane and Cardiac Injury in Hypercholesterolemic Rats. AB - Hypercholesterolemia can increase the risk of cardiac injury, but the underlying mechanisms are not fully understood. The present study aimed to determine whether changes in the fluidity of the cardiomyocyte membrane may contribute to the increased susceptibility to myocardial ischemia/reperfusion (MI/R) injury observed in hypercholesterolemic rats. Male Wistar rats were fed a normal (n = 24) or high-cholesterol diet (n = 32) for 10 weeks. At the 6th week, the rats in the high-cholesterol diet group were treated with vehicle (n = 16, HC + V) or pioglitazone (n = 16, HC + PIO), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, and treatment lasted for the next 4 weeks. Rats in HC + V group displayed less membrane fluidity, a greater membrane cholesterol-to phospholipid ratio (C/P), less Na+-K+-ATPase activity, and less cAMP content in their myocardial cells than rats fed a normal diet. A strong positive correlation was observed between membrane fluidity and cardiac injury, i.e., the myocardial infarct size when subjected to MI/R (30 min/24 h). Treatment with PIO restored much of the lost hypercholesterolemia-induced myocardial cell membrane fluidity, decreased membrane C/P ratio, increased Na+-K+-ATPase activity and cardiac cell cAMP content, improved cardiac function, and reduced the sizes of myocardial infarcts. Results demonstrated that hypercholesterolemia-induced decreased myocardial cell membrane fluidity may contribute to the increased susceptibility to cardiac injury, and PPARgamma agonists may have therapeutic value in patients with hypercholesterolemia. PMID- 26679941 TI - Transdisciplinary Research on Cancer-Healing Systems Between Biomedicine and the Maya of Guatemala: A Tool for Reciprocal Reflexivity in a Multi-Epistemological Setting. AB - Transdisciplinarity (TD) is a participatory research approach in which actors from science and society work closely together. It offers means for promoting knowledge integration and finding solutions to complex societal problems, and can be applied within a multiplicity of epistemic systems. We conducted a TD process from 2011 to 2014 between indigenous Mayan medical specialists from Guatemala and Western biomedical physicians and scientists to study cancer. Given the immense cultural gap between the partners, it was necessary to develop new methods to overcome biases induced by ethnocentric behaviors and power differentials. This article describes this intercultural cooperation and presents a method of reciprocal reflexivity (Bidirectional Emic-Etic tool) developed to overcome them. As a result of application, researchers observed successful knowledge integration at the epistemic level, the social-organizational level, and the communicative level throughout the study. This approach may prove beneficial to others engaged in facilitating participatory health research in complex intercultural settings. PMID- 26679942 TI - Photovoice in Kenya: Using a Community-Based Participatory Research Method to Identify Health Needs. AB - Photovoice, a community-based participatory research method, was utilized to delineate the health-related needs of a small rural community in Kenya. Within the Cherangany Constituency, 13 women were recruited and trained in digital photography and appropriate ethical conduct in photography (respect for privacy, consent, and confidentiality). Both individual and group interviews were conducted with the participants, and data were transcribed and analyzed for common themes by both the participants and the researcher. Common themes present in the photos were coded and prioritized in order of importance: (a) school fees, (b) water, (c) hospital fees, (d) sanitation, (e) orphans, (f) widows, (g) lack of jobs/capital, (h) disabilities, and (i) presence of disease. Data from this study will be utilized for (a) development of culturally competent health education, (b) site-specific education/training of incoming medical teams, and (c) informative meetings with local leaders regarding health and associated challenges. PMID- 26679943 TI - Ionic messengers in development and cancer. AB - The idea that electrical fields can influence the development of an organism is not new. Electrical fields in cells are mainly due to the presence of channels which are permeable and selective for different ions and transporters. Modulation of their activities can affect cell cycle properties, proliferation and differentiation.Electrical fields are important for embryonic patterning, regeneration and tumour development. Membrane potential is a permanent signal which allows communication between cells, tissues and organs and has to be considered to have the same importance as biochemical signals. The activity of ion channels and pumps which maintain the electrical fields can now be dissected and visualized with new tools involving fluorescent reporters.Despite the fact that our understanding, at the molecular level, of the role of bioelectric signaling pathways, ion currents, voltage and pH gradients in developmental biology and tumor progression is increasing, therapeutic applications of this knowledge still appears to be far away. For the moment, research priorities seem to be on establishing the links between biochemical events, genetic regulation, and network interactions. PMID- 26679944 TI - Ion currents involved in gamete physiology. AB - Gametes are electrogenic cells that modify their electrical properties in response to different stimuli. This behavior is due to the occurrence of ion currents flowing through ion channels located on the plasma membranes. The modulation of ion channels has been described during the processes of gamete maturation, activation and fertilization in most of the animal models studied. In particular, predominant ions involved in physiological events in oocyte and sperm have been recognized to be sodium, potassium and calcium. In this review, we give an overview on the occurrence, modulation and function of ion fluxes, from gametogenesis to early fertilization events, from marine animals to human. The implications for a dynamic role of ion currents in gamete physiology and their possible clinical and technological applications are discussed. PMID- 26679945 TI - Calcium signals and oocyte maturation in marine invertebrates. AB - In various oocytes and eggs of animals, transient elevations in cytoplasmic calcium ion concentrations are known to regulate key processes during fertilization and the completion of meiosis. However, whether or not calcium transients also help to reinitiate meiotic progression at the onset of oocyte maturation remains controversial. This article summarizes reports of calcium signals playing essential roles during maturation onset (=germinal vesicle breakdown, GVBD) in several kinds of marine invertebrate oocytes. Conversely, other data from the literature, as well as previously unpublished findings for jellyfish oocytes, fail to support the view that calcium signals are required for GVBD. In addition to assessing the effects of calcium transients on GVBD in marine invertebrate oocytes, the ability of maturing oocytes to enhance their calcium-releasing capabilities after GVBD is also reviewed. Furthermore, possible explanations are proposed for the contradictory results that have been obtained regarding calcium signals during oocyte maturation in marine invertebrates. PMID- 26679946 TI - TRPM channels and magnesium in early embryonic development. AB - Magnesium (Mg(2+)) is the second most abundant cellular cation and is essential for all stages of life, from the early embryo to adult. Mg(2+) deficiency causes or contributes to many human diseases, including migraine headaches, Parkinson's disease, Alzheimer's disease, hypotension, type 2 diabetes mellitus and cardiac arrhythmias. Although the concentration of Mg(2+) in the extracellular environment can vary significantly, the total intracellular Mg(2+) concentration is actively maintained within a relatively narrow range (14 - 20 mM) via tight, yet poorly understood, regulation of intracellular Mg(2+)by Mg(2+) transporters and Mg(2+)-permeant ion channels. Recent studies have continued to add to the growing number of Mg(2+) transporters and ion channels involved in Mg(2+) homeostasis, including TRPM6 and TRPM7, members of the transient receptor potential (TRP) ion channel family. Mutations in TRPM6, including amino acid substitutions that prevent its heterooligomerization with TRPM7, occur in the rare autosomal-recessive disease hypomagnesemia with secondary hypocalcemia (HSH). Genetic ablation of either gene in mice results in early embryonic lethality, raising the question of whether these channels' capacity to mediate Mg(2+) influx plays an important role in embryonic development. Here we review what is known of the function of Mg(2+) in early development and summarize recent findings regarding the function of the TRPM6 and TRPM7 ion channels during embryogenesis. PMID- 26679947 TI - Inhibition of SOCE disrupts cytokinesis in zebrafish embryos via inhibition of cleavage furrow deepening. AB - During the first few cell division cycles in zebrafish, distinct Ca(2+) transients are localized to the early embryonic cleavage furrows, where they accompany (and are required for) furrow positioning, propagation, deepening and apposition. It has previously been shown that the endoplasmic reticulum (ER) acts as the primary store for generating these Ca(2+) transients via release through inositol 1,4,5-trisphosphate receptors (IP 3Rs). We hypothesised that maintaining the elevated levels of intracellular Ca(2+) required for deepening and apposition of the cleavage furrows in these large eggs might result in the depletion of the available ER Ca(2+) store, thus the role of store-operated Ca(2+) entry (SOCE) was examined. Newly fertilized, dechorionated embryos were incubated with various SOCE inhibitors, starting just prior to the onset of the first cell division cycle. The effect of these inhibitors on mitosis, furrow positioning, propagation, deepening and apposition, and the generation of the cytokinetic Ca(2+) transients was determined. Treatment with 2-APB or SKF 96365 had no major effect on mitosis, furrow positioning or propagation, but inhibited furrow deepening resulting in regression of the cleavage furrow. Both of these inhibitors also blocked the furrowing Ca(2+) transient, with SKF 96365 having a more profound inhibitory effect than 2-APB. In zebrafish, SOCE does not appear to be required for mitosis or the early stages of cytokinesis during the early embryonic cell division cycles, but it does appear to be essential for maintaining the elevated levels of [Ca(2+)]i for the extended periods that are required during furrow deepening and daughter cell apposition. PMID- 26679948 TI - Two-Pore Channel 2 activity is required for slow muscle cell-generated Ca(2+) signaling during myogenesis in intact zebrafish. AB - We have recently characterized essential inositol 1,4,5-trisphosphate receptor (IP 3R) and ryanodine receptor (RyR)-mediated Ca(2+) signals generated during the differentiation of slow muscle cells (SMCs) in intact zebrafish embryos. Here, we show that the lysosomal two-pore channel 2 (TPC2) also plays a crucial role in generating, and perhaps triggering, these essential Ca(2+) signals, and thus contributes to the regulation of skeletal muscle myogenesis. We used a transgenic line of zebrafish that expresses the bioluminescent Ca(2+) reporter, aequorin, specifically in skeletal muscle, in conjunction with morpholino (MO)-based and pharmacological inhibition of TPC2, in both intact embryos and isolated SMCs. MO based knock-down of TPC2 resulted in a dramatic attenuation of the Ca(2+) signals, whereas the introduction of TPCN2-MO and TPCN2 mRNA together partially rescued the Ca(2+) signaling signature. Embryos treated with trans-ned-19 or bafilomycin A1, a specific NAADP receptor inhibitor and vacuolar-type H(+)ATPase inhibitor, respectively, also displayed a similar disruption of SMC Ca(2+) signaling. TPC2 and lysosomes were shown via immunohistochemistry and confocal laser scanning microscopy to be localized in perinuclear and striated cytoplasmic domains of SMCs, coincident with patterns of IP 3R and RyR expression. These data together imply that TPC2-mediated Ca(2+) release from lysosomes acts upstream from RyR- and IP 3R-mediated Ca(2+) release, suggesting that the former might act as a sensitive trigger to initiate the SR-mediated Ca(2+)-induced-Ca(2+)-release essential for SMC myogenesis and function. PMID- 26679949 TI - Calcium signals regulated by NAADP and two-pore channels--their role in development, differentiation and cancer. AB - Ca(2+) signals regulate a wide range of physiological processes. Intracellular Ca(2+) stores can be mobilized in response to extracellular stimuli via a range of signal transduction mechanisms, often involving recruitment of diffusible second messenger molecules. The Ca(2+) mobilizing messengers InsP 3 and cADPR release Ca(2+) from the endoplasmic reticulum via InsP 3 and ryanodine receptors, respectively, while a third messenger, NAADP, releases Ca(2+) from acidic endosomes and lysosomes. Bidirectional communication between the ER and acidic organelles has functional relevance for endolysosomal function as well as for the generation of Ca(2+) signals. The two-pore channels (TPCs) are currently strong candidates for being key components of NAADP-regulated Ca(2+) channels. Ca(2+) signals have been shown to play important roles in embryonic development and cell differentiation; however, much remains to be established about the exact signalling mechanisms involved. Investigation of the role of NAADP and TPCs in development and differentiation is still at an early stage, but recent studies have suggested that they play important roles at key developmental stages in vivo and are important mediators of differentiation of neurons, skeletal muscle cells and osteoclasts in vitro. NAADP signals and TPCs have also been implicated in autophagy, an important process in differentiation. Moreover, potential links between TPC2 and cancer have been recently identified. Further studies will be required to identify the precise mechanisms of action of TPCs and their link with NAADP signalling, and to relate these to their roles in differentiation and other key developmental processes in the cell and organism. PMID- 26679950 TI - Na (+)/H (+)exchange in the tumour microenvironment: does NHE1 drive breast cancer carcinogenesis? AB - Ionic messengers signal several critical events in carcinogenesis, including metastasis, the leading cause of patient mortality. The aberrant metabolic, proliferative and anti-apoptotic nature of neoplastic cells can be traced to the abnormal expression of their ion transporters and related signalling networks. In this manuscript, we discuss Na(+)/H(+)flux, as mediated by the sodium-hydrogen exchanger isoform 1 (NHE1), a major ion transporter involved in tumourigenesis. Allosteric activation of NHE1 by external stimuli is controlled by phosphorylation of key amino acids on its cytosolic C-terminal tail, which also acts as a signal scaffold for its regulation by intracellular protein and lipid binding partners. In breast cancer cells, pH homeostasis and proton dynamics are disrupted early in transformation. This constitutively activates NHE1, causing a reversal of the plasma membrane pH gradient, resulting in a more alkaline intracellular pH and a more acidic extracellular pH. NHE1-mediated cellular alkalinization potentiates cytoskeletal remodelling, mobilizing cells for directed migration. Concomitant redistribution of NHE1 to invadopodia, where increased proton extrusion promotes proteolytic digestion of the extracellular matrix, primes cells for invasion into the bloodstream. NHE1 hyperactivity therefore heralds an important stage in cancer cell development, critically facilitating the acquisition of the invasive phenotype necessary for metastasis to occur. The potential for targeting NHE1 in the development of novel chemotherapeutic applications is explored. PMID- 26679951 TI - Calcium signaling and cell fate: how can Ca2+ signals contribute to wrong decisions for Chronic Lymphocytic Leukemic B lymphocyte outcome? AB - Ca(2+) signaling is a key regulator of B lymphocyte cell fate and defects in this signaling pathway have been reported in numerous diseases such as Chronic lymphocytic leukemia (CLL). CLL is a B cell clonal disorder characterized by the accumulation of mature monoclonal CD5(+) B cells. Although CLL could be considered to be a proliferative disease, most circulating CLL B cells are arrested in the G0 phase of the cell cycle and present both defects in calcium (Ca(2+)) homeostasis and signaling. The Ca(2+) response to antigen ligation is heterogeneous and related, in part, to defects arising from the incapacity to respond to B cell receptor (BCR) engagement (anergy), to the expression of T cell kinases (e.g. Zap70), and to the presence of negative feedback regulation by phosphatases (e.g. SHP-1). Anergic CD5(+) CLL B cells are characterized by an elevated basal Ca(2+) level, IgM/CD79 downregulation, a constitutive activation of BCR pathway kinases, and an activation of the nuclear factor of activated T cells (NF-AT). Based on the Ca(2+) response, patients are classified into three groups: unresponders, responders with apoptosis, and responders with entry in the cell cycle. Moreover, internal and direct interaction between leukemic BCR-HCDR3 epitopes at the plasma membrane and interaction between Bcl-2 and the IP3 receptor at the endoplasmic reticulum are also suspected to interfere with the intracellular Ca(2+) homeostasis in CLL-B cells. As a whole, the Ca(2+) pathway is emerging to play a key role in malignant CLL-B survival, disease progression, and last but not least, in the therapeutic response. PMID- 26679952 TI - Human transient receptor potential (TRP) channel expression profiling in carcinogenesis. AB - Despite the intensive research of the last three decades into Transient Receptor Potential (TRP) cation channels, no precise and complete profiling of these channels is yet available regarding their involvement in physiopathology and carcinogenesis in particular. TRP channel activity is crucial for all the essential hallmarks of carcinogenesis such as proliferation, apoptosis, migration and angiogenesis, which is the reason why these channels have been proposed not only as clinical markers, but also as promising targets for anti-cancer therapy. However, in the majority of studies, each channel has been considered as a separate molecular entity and studied independently from the other TRPs, while a complete "transportome" of the specific stages of carcinogenesis is required for the effective use of these targets. This review focuses on the partial TRP expression profiles found in the literature and the means by which a full TRP signature could be achieved. PMID- 26679953 TI - Glioblastoma and calcium signaling--analysis of calcium toolbox expression. AB - The characteristics of a cellular calcium signal (calcium signature) are determined, at least partly, by the expression of a subset of genes encoding proteins involved in calcium entry, calcium uptake and calcium modulation. Our aim in the present work was to characterize the set of genes involved in calcium signal generation that are differentially expressed in normal brain tissues versus brain tumor and/or glioma stem cells. Public datasets were analyzed according to a four step methodology consisting of: 1. detecting the outliers by using principal component analysis of the whole transcriptome; 2. building a calcium toolbox composed of 260 genes involved in the generation and modulation of the calcium signal; 3. analyzing the calcium toolbox transcriptome of different human brain areas and 4. detecting genes from the calcium toolbox preferentially expressed in tumor tissues or tumor cells compared to normal brain tissues. Our approach was validated on normal brain tissue. Tumor sample analysis allowed us to disclose a set of eighteen genes characteristic of glioblastoma tissues or glioma stem cells. Interpreting the set of genes highlighted in the study led us to propose that i) the mechanism of store operated calcium entry is strongly perturbed in cancer cells and tissues, ii) the process of calcium reuptake into mitochondria is more important in cancer cells and tissues than in their normal counterparts and iii) these two mechanisms may be coupled in at least one subgroup of the glioblastoma stem cells. PMID- 26679954 TI - On the interplay between academic achievement and educational identity: a longitudinal study. AB - The present three-wave longitudinal study provides empirical evidence for the mechanisms of the bright and dark sides of identity development in the academic context. First, we investigated the patterns of stability and change in educational identity and academic achievement among adolescents. Second, we examined the reciprocal associations between identity processes (i.e., commitment, in-depth exploration, and reconsideration of commitment) and academic achievement. The main results of the study highlighted that academic achievement predicts the manner in which adolescents deal with their identity issues in the academic context. Thus, high academic achievement leads to high levels of commitment (identity synthesis), while low academic achievement leads to high levels of reconsideration of commitment (identity confusion). This unidirectional pattern of effects applied equally to adolescent boys and girls, early-to-middle and middle-to-late adolescents, and to adolescents attending theoretical and vocational schools. Practical implications are discussed. PMID- 26679955 TI - Effect of Aggression Regulation on Eating Disorder Pathology: RCT of a Brief Body and Movement Oriented Intervention. AB - OBJECTIVE: The objective of the study is to evaluate the effect of a brief body and movement oriented intervention on aggression regulation and eating disorder pathology for individuals with eating disorders. METHOD: In a first randomized controlled trial, 40 women were allocated to either the aggression regulation intervention plus supportive contact or a control condition of supportive contact only. The intervention was delivered by a psychomotor therapist. Participants completed questionnaires on anger coping and eating disorder pathology. Independent samples t-tests were performed on the difference between pre treatment and post-treatment scores. RESULTS: Twenty-nine participants completed questionnaires at pre-intervention and post-intervention. The intervention resulted in a significantly greater improvement of anger coping, as well as of eating disorder pathology. DISCUSSION: Results indicate that body and movement oriented aggression regulation may be a viable add-on for treating eating disorders. It tackles a difficult to treat emotion which may have a role in blocking the entire process of treating eating disorders. PMID- 26679956 TI - A unique duplication of gene cluster (S2-C-Y) in Epopella plicata (Crustacea) mitochondrial genome and phylogeny within Cirripedia. AB - Barnacles (Crustacea: Cirripedia) are important model species in invertebrate larval biology, intertidal ecology, and anti-fouling researches. The complete mitochondrial genome of the intertidal barnacle Epopella plicata Gray, 1843 (Cirripedia: Sessilia: Tetraclitidae) is presented. The mitochondrial genome of E. plicata of 15 296 bp in length encodes 13 PCGs, 2 rRNA genes, and 25 tRNA genes. The genome of E. plicata has a duplicate gene cluster (trnS2-trnC-trnY) that is unique in the infraclass Cirripedia. The two copies of trnC share identical sequences, but nucleotide substitutions are observed in the other two pairs of tRNAs. Comparison of the two trnS2 indicates that DHU arm and acceptor stem have nucleotide variation. In the two trnY, nucleotide variations are found in the acceptor stem, TpsiC arm, DHU arm, and variable loop. However, there is no nucleotide variation in the anticodon arm of the three tRNAs. Epopella plicata mitochondrial genome shares seven gene rearrangements with that of Tetraclita japonica (Tetraclitidae), including trnK, trnA, trnE/trnS1, trnP/trnT, trnI/trnQ, trnY and trnC. Comparison of gene orders in the two tetraclitid barnacles and the pancrustacean ground pattern suggests that the arrangement of E. plicata mitochondrial genome is a derived character in this species within the family Tetraclitidae. Sequence analysis of all available barnacle mitochondrial genomes shows that within the order Sessilia, E. plicata and Tetraclita japonica cluster together, resulting in monophyly of Tetraclitidae. Notochthamalus scabrosus (Chthamalidae) is at the basal position of the order Sessilia. Monophyly of the family Balanidae was questioned based on both gene order comparison and sequence analyses, and its phylogenetic status needs to be elucidated further. PMID- 26679957 TI - Morphometric analysis of the medial opticocarotid recess and its anatomical relations relevant to the transsphenoidal endoscopic endonasal approaches. AB - BACKGROUND: The medial opticocarotid recess (MOCR) is located in the posterior wall of the sphenoid sinus, medial to the junction of the optic canal (OC) and the carotid prominence (CP). There is controversy in the literature in relation to the presence of the MOCR and its constancy, which is relevant when approaching the skull base through an endoscopic route. METHODS: The morphometric relations of the MOCR with the surrounding structures were studied in 18 cadaveric specimens after endoscopic endonasal approach (EEA). RESULTS: The distance between both MOCR was 11.06 +/- 1.14 mm; the distance between the MOCR and the lateral opticocarotid (LOCR) recess was 5.56 +/- 0.85 mm; the distance between the MOCR and the suprasellar recess was 3.72 +/- 0.49 mm; the angle between the MOCR plane and the OC 13.32 +/- 2.30 degrees ; the angle between the MOCR plane and the CP 13.50 +/- 2.68 degrees and; the angle between the OC and the CP 26.81 +/- 4.26 degrees . All measurements showed low variability, with low standard deviation and interquartile range. No relations were found between any of the measurements. CONCLUSIONS: The MOCR may be used as a reference point for precise location of structures during EEA. Objective measurements may be especially useful in cases with distorted sphenoid bone anatomy. PMID- 26679958 TI - In-Situ Probing Plasmonic Energy Transfer in Cu(In, Ga)Se2 Solar Cells by Ultrabroadband Femtosecond Pump-Probe Spectroscopy. AB - In this work, we demonstrated a viable experimental scheme for in-situ probing the effects of Au nanoparticles (NPs) incorporation on plasmonic energy transfer in Cu(In, Ga)Se2 (CIGS) solar cells by elaborately analyzing the lifetimes and zero moment for hot carrier relaxation with ultrabroadband femtosecond pump-probe spectroscopy. The signals of enhanced photobleach (PB) and waned photoinduced absorption (PIA) attributable to surface plasmon resonance (SPR) of Au NPs were in-situ probed in transient differential absorption spectra. The results suggested that substantial carriers can be excited from ground state to lower excitation energy levels, which can reach thermalization much faster with the existence of SPR. Thus, direct electron transfer (DET) could be implemented to enhance the photocurrent of CIGS solar cells. Furthermore, based on the extracted hot carrier lifetimes, it was confirmed that the improved electrical transport might have been resulted primarily from the reduction in the surface recombination of photoinduced carriers through enhanced local electromagnetic field (LEMF). Finally, theoretical calculation for resonant energy transfer (RET) induced enhancement in the probability of exciting electron-hole pairs was conducted and the results agreed well with the enhanced PB peak of transient differential absorption in plasmonic CIGS film. These results indicate that plasmonic energy transfer is a viable approach to boost high-efficiency CIGS solar cells. PMID- 26679959 TI - Trends in molecular epidemiology of drug-resistant tuberculosis in Republic of Karelia, Russian Federation. AB - BACKGROUND: Russian Republic of Karelia is located at the Russian-Finnish border. It contains most of the historical Karelia land inhabited with autochthonous Karels and more recently migrated Russians. Although tuberculosis (TB) incidence in Karelia is decreasing, it remains high (45.8/100 000 in 2014) with the rate of multi-drug resistance (MDR) among newly diagnosed TB patients reaching 46.5 %. The study aimed to genetically characterize Mycobacterium tuberculosis isolates obtained at different time points from TB patients from Karelia to gain insight into the phylogeographic specificity of the circulating genotypes and to assess trends in evolution of drug resistant subpopulations. METHODS: The sample included 150 M. tuberculosis isolates: 78 isolated in 2013-2014 ("new" collection) and 72 isolated in 2006 ("old" collection). Drug susceptibility testing was done by the method of absolute concentrations. Spoligotyping was used to test genotype-specific markers of a Latin-American-Mediterranean (LAM) family and its sublineages as well as a Beijing B0/W148-cluster. RESULTS: The largest spoligotypes were SIT1 (Beijing family, n = 42) and SIT40 (T family, n = 5). Beijing family was the largest (n = 43) followed by T (n = 11), Ural (n = 10) and LAM (n = 8). Successful Russian clone, Beijing V0/W148, was identified in 15 (34.9 %) of 43 Beijing isolates; all V0/W148 isolates were drug-resistant. Seven of 8 LAM isolates belonged to the RD115/LAM-RUS branch, 1 - to the LAM RD174/RD Rio sublineage. MDR was found in Beijing (32/43), Ural (3/10), and LAM (3/8). In contrast, all T isolates were pansusceptible. Comparison of drug resistant subgroups of the new and old collections showed an increasing prevalence of the B0/W148 clonal cluster, from 18.0 % (mainly polyresistant) in 2006 to 32.6 % in 2014 (mainly MDR and pre-XDR). The West-east increasing gradient is observed for the Ural genotype that may be defined a 'Russian' strain. In contrast, the spoligotype SIT40 of the T family appears to be a historical Karelian strain. CONCLUSIONS: Circulation of the MDR M. tuberculosis isolates of the Beijing genotype and its B0/W148 cluster continues to critically influence the current situation with the MDR-TB control in northwestern Russia including the Republic of Karelia. Revealed phylogeographic patterns of some genotypes reflect a complex demographic history of Karelia within the course of the 20(th) century. PMID- 26679961 TI - Proceedings of the AMCP Partnership Forum: Breaking the Link Between Pain Management and Opioid Use Disorder. AB - Prescription drug misuse and abuse, especially with opioid analgesics, is the fastest growing drug problem in the United States. Addressing this public health crisis demands the coordinated efforts and actions of all stakeholders to establish a process of improving patient care and decreasing misuse and abuse. On September 9, 2014, the Academy of Managed Care Pharmacy (AMCP) convened a meeting of multiple stakeholders to recommend activities and programs that AMCP can promote to improve pain management, prevent opioid use disorder (OUD), and improve medication-assisted treatment outcomes. The speakers and panelists recommended that efforts to improve pain management outcomes and reduce the potential for OUD should rely on demonstrated evidence and best practices. It was recommended that AMCP promote a more holistic and evidence-based approach to pain management and OUD treatment that actively engages the patient in the decision making process and includes care coordination with medical, pharmacy, behavioral, and mental health aspects of organizations, all of which is seamlessly supported by a technology infrastructure. To accomplish this, it was recommended that AMCP work to collaborate with organizations representing these stakeholders. Additionally, it was recommended that AMCP conduct continuing pharmacy education programs, develop a best practices toolkit on pain management, and actively promote quality standards for OUD prevention and treatment. PMID- 26679960 TI - Clinical and Economic Burden of Commercially Insured Patients with Acromegaly in the United States: A Retrospective Analysis. AB - BACKGROUND: Acromegaly is a chronic disorder characterized by excess growth hormone secretion and elevated insulin-like growth factor-1 levels most often caused by a pituitary adenoma. Clinical presentation of the disease includes coarsening of the facial features, soft-tissue swelling of the hands and feet, and overgrowth of the frontal skull and protrusion of the jaw, as well as joint symptoms. Acromegaly is associated with several comorbidities, including diabetes, cardiovascular disease, and arthropathy, which, if left untreated, can lead to early mortality. Surgery to remove the adenoma is the first-line treatment for many patients, but more than 50% of patients will require additional pharmacologic or radiation therapy. OBJECTIVES: To (a) determine the clinical and economic burden of illness among patients with acromegaly using administrative claims data from a large, commercially insured population in the United States and (b) estimate the most frequent acromegaly-related comorbidities and health care resource utilization and costs among these patients. METHODS: This retrospective, observational cohort study used administrative claims data from the HealthCore Integrated Research Database, containing a geographically diverse spectrum of longitudinal claims data from the largest database of commercially insured patients in the United States. Patients were aged >= 20 years and fulfilled >= 1 of the following criteria during the intake period (March 31, 2008-July 31, 2012): >= 2 independent diagnostic codes for acromegaly, >= 1 acromegaly diagnosis code and >= 1 acromegaly-related procedure code, or >= 1 acromegaly diagnosis code and >= 1 medical claim for acromegaly-related therapy. The index date was defined as the date of the first medical claim for acromegaly within the intake period. Assessed outcomes included prevalence of acromegaly diagnosis and incidence of new acromegaly diagnoses during the study period (January 1, 2008-July 31, 2013), acromegaly-related comorbidities, and pharmacotherapy use. Because 2008 and 2012 data were incomplete, incidence rates were only reported for 2009, 2010, and 2011. Total and acromegaly-related health care resource utilization and annual health care costs were analyzed during a 12 month post-index observational period. RESULTS: In total, 757 patients with acromegaly met the selection criteria for this study, with a mean age of 49.3 years (53.6% female). The total prevalence of acromegaly was 41.7 cases per million. Acromegaly incidence was 15.0, 13.3, and 9.5 cases per million in 2009, 2010, and 2011, respectively. The top 5 acromegaly-related comorbidities were hypertension, diabetes, hypothyroidism, arthropathy/arthralgia/synovitis, and sleep apnea. During the study period, 51% of patients (n = 385) used acromegaly related pharmacologic therapy, with the most common being cabergoline and octreotide (used by 12.4% and 12.2% of patients, respectively). Overall, 18.8% of patients incurred an acromegaly-related inpatient stay; 97.0% used outpatient services other than emergency room (ER) or physician visits; 74.8% had a physician office visit; and 1.8% visited the ER for acromegaly-related reasons. In the 12-month post-index period, 37.0% of patients filed claims for acromegaly related prescription drugs, and patients with greater than 1 claim had an average of 7.6 prescriptions. The most expensive acromegaly-related costs in this study population were inpatient hospitalizations ($6,754) and prescription drugs ($6,147). CONCLUSIONS: Consistent with previous studies, this study confirms that acromegaly is a rare condition associated with multiple comorbidities. Notably, 18.8% of this study population required an inpatient hospital admission during the 12-month post-index period, possibly because of severe comorbidities. Because acromegaly-related costs were driven by hospitalizations and pharmacotherapy, improved management of the disease may reduce the clinical and economic burden experienced by patients with acromegaly. PMID- 26679962 TI - Asthma Controller Medication Adherence, Risk of Exacerbation, and Use of Rescue Agents Among Texas Medicaid Patients with Persistent Asthma. AB - BACKGROUND: Adherence to asthma long-term controller medications is one of the key drivers to improve asthma management among patients with persistent asthma. While suboptimal use of controller medications has been found to be associated with more frequent use of oral corticosteroids (OCS), few studies exist regarding the relationship between adherence to controller therapy and the use of short acting beta2-agonists (SABAs). A better understanding of the association between adherence to asthma controller agents and use of reliever medications will help health care providers and decision makers enhance asthma management. OBJECTIVE: To determine if there is a relationship between asthma controller adherence, risk of exacerbation requiring OCS, and use of asthma rescue agents. METHODS: Texas Medicaid claims data from January 1, 2008, to August 31, 2011, were retrospectively analyzed. Continuously enrolled patients aged 5-63 years with a primary diagnosis of asthma (ICD-9-CM code 493) and with 4 or more prescription claims for any asthma medication in 1 year (persistent asthma) were included. The index date was the date of the first asthma controller prescription, and patients were followed for 1 year. The primary outcome variables were SABA (dichotomous: less than 6 vs. >= 6) and OCS (continuous) use. The primary independent variable was adherence (proportion of days covered [PDC]) to asthma long-term controller medications. Covariates included demographics and nonstudy medication utilization. Multivariate logistic and linear regression analyses were employed to address the study objective. RESULTS: The study sample (n = 32,172) was aged 15.0 +/- 14.5 years, and adherence to controller therapy was 32.2% +/- 19.7%. The mean number of SABA claims was 3.7 +/- 3.1, with most patients having 1-5 claims (73.2%), whereas 19.4% had >= 6 SABA claims. The mean number of OCS claims was 1.0 +/- 1.4. Adherent (PDC >= 50%) patients were 96.7% (OR = 1.967; 95% CI = 1.826-2.120) more likely to have >= 6 SABA claims when compared with nonadherent (PDC less than 50%) patients (P less than 0.001). As for OCS use, adherent patients had 0.11 fewer claims compared with nonadherent patients (P less than 0.001). Importantly, patients with >= 6 SABA claims had 0.7 more OCS claims compared with patients with less than 6 claims for SABA (P less than 0.001). The odds of having >= 6 SABA claims were higher for concurrent dual therapy users, older age, males, African Americans and higher number of nonstudy medications (P less than 0.001). Dual therapy users, younger age, Hispanic ethnicity, and higher number of nonstudy medications were associated with an increase in OCS use (P less than 0.005). CONCLUSIONS: Adherence to long-term controller medications was suboptimal among patients with asthma. Adherent patients had fewer OCS claims, indicating that adherence to controller therapy is critical in preventing asthma exacerbations requiring OCS use. Although there was a positive relationship between adherence to long-term controller medication and SABA use, increased SABA use served as a predictor of increased OCS use, which indicates poor asthma control. Health care providers should be aware of OCS and SABA use among patients who are both adherent and nonadherent to asthma controller medications. PMID- 26679963 TI - A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes. AB - BACKGROUND: Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations. OBJECTIVE: To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs. METHODS: All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total. RESULTS: The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However, other EPCs with median scores of 75 and above included hepatitis C virus NS3/4A protease inhibitor, recombinant human interferon beta, vascular endothelial growth factor directed antibody, and tumor necrosis factor blocker. When Anatomical Therapeutic Chemical classifications were analyzed, antineoplastic drugs were outliers with approximately 80% of their individual scores 60 and above, while approximately 20%-30% of blood and anti-infective drugs had scores of 60 and above. Within-drug class results served to differentiate similar drugs. For example, 6 serotonin reuptake inhibitors had a score range of 35 to 53. CONCLUSIONS: This scoring system is based on estimated direct medical costs associated with postmarketing AEs and poor patient outcomes and thereby helps fill a large information gap regarding drug safety in real-world patient populations. PMID- 26679964 TI - Development and Validation of a Predictive Model to Identify Individuals Likely to Have Undiagnosed Chronic Obstructive Pulmonary Disease Using an Administrative Claims Database. AB - BACKGROUND: Despite the importance of early detection, delayed diagnosis of chronic obstructive pulmonary disease (COPD) is relatively common. Approximately 12 million people in the United States have undiagnosed COPD. Diagnosis of COPD is essential for the timely implementation of interventions, such as smoking cessation programs, drug therapies, and pulmonary rehabilitation, which are aimed at improving outcomes and slowing disease progression. OBJECTIVE: To develop and validate a predictive model to identify patients likely to have undiagnosed COPD using administrative claims data. METHODS: A predictive model was developed and validated utilizing a retro-spective cohort of patients with and without a COPD diagnosis (cases and controls), aged 40-89, with a minimum of 24 months of continuous health plan enrollment (Medicare Advantage Prescription Drug [MAPD] and commercial plans), and identified between January 1, 2009, and December 31, 2012, using Humana's claims database. Stratified random sampling based on plan type (commercial or MAPD) and index year was performed to ensure that cases and controls had a similar distribution of these variables. Cases and controls were compared to identify demographic, clinical, and health care resource utilization (HCRU) characteristics associated with a COPD diagnosis. Stepwise logistic regression (SLR), neural networking, and decision trees were used to develop a series of models. The models were trained, validated, and tested on randomly partitioned subsets of the sample (Training, Validation, and Test data subsets). Measures used to evaluate and compare the models included area under the curve (AUC); index of the receiver operating characteristics (ROC) curve; sensitivity, specificity, positive predictive value (PPV); and negative predictive value (NPV). The optimal model was selected based on AUC index on the Test data subset. RESULTS: A total of 50,880 cases and 50,880 controls were included, with MAPD patients comprising 92% of the study population. Compared with controls, cases had a statistically significantly higher comorbidity burden and HCRU (including hospitalizations, emergency room visits, and medical procedures). The optimal predictive model was generated using SLR, which included 34 variables that were statistically significantly associated with a COPD diagnosis. After adjusting for covariates, anticholinergic bronchodilators (OR = 3.336) and tobacco cessation counseling (OR = 2.871) were found to have a large influence on the model. The final predictive model had an AUC of 0.754, sensitivity of 60%, specificity of 78%, PPV of 73%, and an NPV of 66%. CONCLUSIONS: This claims-based predictive model provides an acceptable level of accuracy in identifying patients likely to have undiagnosed COPD in a large national health plan. Identification of patients with undiagnosed COPD may enable timely management and lead to improved health outcomes and reduced COPD-related health care expenditures. PMID- 26679965 TI - Prevalence of Low-Cost Generic Program Use in a Nationally Representative Cohort of Privately Insured Adults. AB - BACKGROUND: Administrative claims data are used for a wide variety of research and quality assurance purposes. Despite their utility, they are prone to medication exposure misclassification if medications are purchased without utilizing an insurance benefit. Low-cost generic programs (LCGPs) offered at major chain pharmacies are a relatively new and sparsely investigated source of exposure misclassification. Since they were implemented in 2006, LCGPs are now available at 8 of the 10 largest pharmacy chains and include a wide variety of medication classes. LCGP medications are often purchased out of pocket; thus, a pharmacy claim may never be submitted and exposure may go unobserved in claims data. There are little data regarding the utilization of these programs, and estimates of their use can provide important insights into the potential impact LCGPs may have on exposure misclassification in claims data. OBJECTIVES: To (a) quantify the prevalence of LCGP users in a privately insured adult population, (b) assess patterns of LCGP use, and (c) compare clinical and demographic characteristics associated with LCGP users and nonusers. METHODS: The study cohort consisted of 19,037 privately insured adults aged 18-64 who participated in the Medical Expenditure Panel Survey (MEPS) from 2007-2011. MEPS captures medication utilization at the pharmacy level, so prescription fills can be observed irrespective of a claim being filed. Pharmaceutical utilization was assessed at the individual level for each year of the study period, and LCGP use was recorded as a binary variable for each individual. An LCGP medication fill was identified if the total cost of the drug was paid out of pocket and matched the cost of medications listed on LCGP formularies available from Target, Walmart, CVS, or other major pharmacy retailers during these years. Cohort demographics and characteristics of interest included age, gender, race, employment status, marital status, family income, education level, residence in a metropolitan statistical area (MSA), prescription drug coverage, geographic region, comorbidities, and number of unique medications and medication fills. Comparisons were made between users and nonusers using chi-square and t-tests. Multivariable logistic regression was used to identify factors associated with LCGP use. RESULTS: Out of the entire study cohort (N = 19,037), 6,921 (36.4%) individuals were identified as LCGP users, representing 34 million LCGP users annually. Users tended to be older, had higher Charlson Comorbidity Index scores, filled more prescriptions per person, and used more unique medications. Proportions of LCGP users and uses nearly doubled from 2007-2011, while total prescription utilization per person remained relatively stable. Over 10% of all prescription fills were filled through LCGPs. Of all LCGP fills, approximately 42% were for cardiovascular medications, 12% for antidiabetics, and 14% for levothyroxine. Greater than 30% of fills for antigout, metronidazole, angiotensin converting enzyme inhibitors, levothyroxine, metformin, and diuretics were obtained through LCGPs, as were 18.9% of all warfarin fills. Compared with the reference category aged 18-34, adults aged 35-54 had an adjusted odds ratio (AOR) of being an LCGP user of 1.39 (95% CI = 1.29-1.50) and adults aged 55-64 had an AOR of 1.86 (95% CI = 1.70-2.04). Additionally, those with prescription drug coverage were nearly twice as likely to be LCGP users (AOR = 1.96; 95% CI = 1.64 2.35) compared with those without. Gender, income, comorbidity burden, region, year of panel entry, and number of unique medications also significantly predicted LCGP use. CONCLUSIONS: There is a high rate of LCGP use in the privately insured adult population. Users of LCGPs tend to be older, have more chronic comorbidities, and use more medications than nonusers. Claims-based research and quality assurance programs focusing on the benefits and harms of medications available through these programs are at risk of greatly underestimating the true medication exposure in this population and should account for this in sensitivity analyses. Managed care organizations should incentivize the reporting of LCGP medication use or make adjustments to generic medication benefit structures to more effectively capture true medication exposure. PMID- 26679966 TI - Health Outcomes Associated with Initiation of Basal Insulin After 1, 2, or >= 3 Oral Antidiabetes Drug(s) Among Managed Care Patients with Type 2 Diabetes. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive disease. Despite starting with single oral antidiabetes drug (OAD) therapy and then adding OAD(s), most patients eventually require insulin therapy to achieve and maintain glycemic control. The timely initiation of insulin therapy could help patients with T2DM whose glycemic control is not adequately maintained using OADs alone. OBJECTIVE: To describe and compare baseline characteristics and assess real-world health outcomes associated with initiating basal insulin after 1 OAD, 2 OADs, or >= 3 OADs among T2DM patients. METHODS: Data were analyzed from adult T2DM patients in a U.S. managed care claims database (IMPACT) who initiated a basal insulin (from January 1, 2001, to December 31, 2011) with continuous health plan enrollment for 6 months before (baseline) and 12 months after (follow-up) insulin initiation and who had at least 1 OAD prescription. Outcome measures according to the number of OADs used were (a) treatment discontinuation, (b) glycated hemoglobin (A1c) levels, (c) proportion of patients experiencing hypoglycemia, (d) health care resource utilization, and (e) costs. RESULTS: Data from 71,988 patients were included (1 OAD: 19,168 patients [26.6%]; 2 OADs: 29,112 [40.4%]; and >= 3 OADs: 23,708 [32.9%]). All baseline characteristics, except nephropathy, were significantly different across the 3 groups. At baseline, when compared with the 1 OAD or 2 OADs groups, the >=3 OADs group was less likely to be female or have macrovascular disease and had experienced fewer hypoglycemic events and hospitalization as well as lower costs. At follow-up, treatment discontinuation rates were 36.0%, 27.6%, and 21.4% for the 1 OAD, 2 OADs, and >= 3 OADs groups, respectively. A1c reduction was -1.33%, -1.05%, and -0.86%, respectively. The proportion of patients experiencing any hypoglycemia was 4.7%, 3.8%, and 3.3% at baseline; and 3.7%, 3.5%, and 3.1% at follow-up for the 1 OAD, 2 OADs, and >=3 OADs groups, respectively. In all 3 groups, health care costs decreased compared with baseline, particularly in the 1 OAD and 2 OADs groups, with decreased inpatient costs offsetting increased drug costs. CONCLUSIONS: This real-world analysis shows that there are significant baseline differences in patients with T2DM on 1 OAD, 2 OADs, or >=3 OADs when adding insulin therapy. All 3 groups had significant improvements in clinical and economic outcomes compared with baseline, yet at different magnitudes. These data contribute to a growing body of evidence supporting the timely initiation of insulin therapy for T2DM patients not maintaining glycemic control with OADs. PMID- 26679967 TI - A Real-World Observational Study of Time to Treatment Intensification Among Elderly Patients with Inadequately Controlled Type 2 Diabetes Mellitus. AB - BACKGROUND: Among elderly patients, the management of type 2 diabetes mellitus (T2DM) is complicated by population heterogeneity and elderly-specific complexities. Few studies have been done to understand treatment intensification among elderly patients failing multiple oral antidiabetic drugs (OADs). OBJECTIVE: To examine the association between time to treatment intensification of T2DM and elderly-specific patient complexities. METHODS: In this observational, retrospective cohort study, elderly (aged >= 65 years) Medicare beneficiaries (n = 16,653) with inadequately controlled T2DM (hemoglobin A1c >= 8.0% despite 2 OADs) were included. Based on the consensus statement for diabetes care in elderly patients published by the American Diabetes Association and the American Geriatric Society, elderly-specific patient complexities were defined as the presence or absence of 5 geriatric syndromes: cognitive impairment; depression; falls and fall risk; polypharmacy; and urinary incontinence. RESULTS: Overall, 48.7% of patients received intensified treatment during follow-up, with median time to intensification 18.5 months (95% CI = 17.7-19.3). Median time to treatment intensification was shorter for elderly patients with T2DM with polypharmacy (16.5 months) and falls and fall risk (12.7 months) versus those without polypharmacy (20.4 months) and no fall risk (18.6 months). Elderly patients with urinary incontinence had a longer median time to treatment intensification (18.6 months) versus those without urinary incontinence (14.6 months). The median time to treatment intensification did not significantly differ by the elderly-specific patient complexities that included cognitive impairment and depression. However, after adjusting for demographic, insurance, clinical characteristics, and health care utilization, we found that only polypharmacy was associated with time to treatment intensification (adjusted hazard ratio, 1.10; 95% CI = 1.04-1.15; P = 0.001). CONCLUSIONS: Less than half of elderly patients with inadequately controlled T2DM received treatment intensification. Elderly-specific patient complexities were not associated with time to treatment intensification, emphasizing a positive effect of the integrated health care delivery model. Emerging health care delivery models that target integrated care may be crucial in providing appropriate treatment for elderly T2DM patients with complex conditions. PMID- 26679968 TI - Geographic Variation in Antidiabetic Agent Adherence and Glycemic Control Among Patients with Type 2 Diabetes. AB - BACKGROUND: Medication nonadherence is an imperative public health concern. Among patients with type 2 diabetes mellitus (T2DM), poor adherence to antidiabetic agents is strongly associated with suboptimal glycemic control. Poor adherence and hyperglycemia greatly increase diabetes-related morbidity and mortality. At a national level, diabetes drug adherence using average proportion of days covered (PDC) is estimated to range between 36% and 81%, with an estimated range for diabetes control between 38% and 47%. At a state level no such studies exist. OBJECTIVE: To estimate the level of medication adherence to antidiabetic agents and of diabetes control, and their association among patients with T2DM receiving medication treatment at the state and the Metropolitan Statistical Area (MSA) levels among the populations covered by commercial insurance, Medicare, or Medicaid. METHODS: The study population included adults with T2DM aged >=18 years who were identified using ICD-9-CM code 250.xx, who received diabetes medication, and who were covered by private insurance, Medicare, or Medicaid in each state, the District of Columbia, and the top 50 MSAs. Medication adherence was measured by average PDC and the percentage of population that had a PDC >= 80%. Diabetes control was identified using ICD-9-CM diagnosis codes. Patients who were not diagnosed with uncontrolled diabetes (250.x2 and 250.x3) were identified as being under control. The administrative claims databases used for this study included the 2012 medical and pharmacy claims from a large U.S. health plan, the complete 2011 Medicare Standard Analytical File linked with Part D claims, and the 2008 Mini-Medicaid Analytic eXtract (Mini-Max). Medication adherence and diabetes control were adjusted for age and sex to allow comparison across insurance coverage, states, and MSAs. RESULTS: For an insured patient population with T2DM that received diabetic drug treatment, average PDC was 79%. However, 35% of patients did not achieve an adherence of at least 80% of PDC. In addition, at least 40% of patients did not have their diabetes under control. Across insurance types, we found that patients insured with Medicare had relatively high average PDC and adherence levels (83% and 71%) in comparison with the commercially insured population (77% and 60%) and Medicaid patients (75% and 57%). In contrast, commercially insured patients had relatively better diabetes control (69%) than those insured with Medicare and Medicaid (54% and 53%, respectively). At a state level, we found that commercially insured and Medicare populations have relatively smaller geographic variation in drug adherence than the Medicaid population. CONCLUSIONS: This study identified gaps in T2DM drug adherence and pinpointed geographic areas that lag in terms of diabetes drug adherence or diabetes control and would benefit from implementing strategies to increase drug adherence. PMID- 26679969 TI - Demographic and Clinical Profiles of Type 2 Diabetes Mellitus Patients Initiating Canagliflozin Versus DPP-4 Inhibitors in a Large U.S. Managed Care Population. AB - BACKGROUND: Canagliflozin is the first sodium-glucose co-transporter-2 (SGLT-2) inhibitor-a new class of oral antidiabetic (OAD) medication-approved for type 2 diabetes mellitus (T2DM) treatment in the United States. Approved less than 2 years ago, use of canagliflozin is largely uncharacterized. OBJECTIVE: To investigate and compare baseline demographic, clinical, and economic characteristics of patients initiating canagliflozin and dipeptidyl peptidase-4 (DPP-4) inhibitors in the real-world setting. METHODS: Using administrative claims data from a large, geographically diverse U.S. managed care organization, this retrospective study assessed adult T2DM patients (aged >= 18 years) initiating treatment with canagli-flozin or DPP-4 agents. Eligible patients had >=1 medical claim with a T2DM diagnosis and >= 1 outpatient pharmacy claim for canagliflozin or a DPP-4 agent between January 1, 2011, and September 30, 2013. Patients with >= 1 canagliflozin fill were selected first and assigned to the canagliflozin cohort following a hierarchical approach; the date of the earliest canagliflozin fill was defined as the index date. Remaining patients with DPP-4 fills were then assigned to the DPP-4 cohort, with the index date as the first DPP-4 fill. Only patients with at least 12 months of pre-index (baseline) enrollment were included. Patients with fills for their cohort-defining drug over 3 months before the index date were excluded in order to focus on new initiators. A subset of patients with >= 3 months of continuous enrollment following their index dates was used to examine medication patterns after initiation. Patients with hyperglycemia; type 1, gestational, or nonclinical diabetes; or diabetes with hyperosmolar coma were excluded. Demographic, clinical, and economic characteristics were assessed over baseline and compared using two-sample t-tests or chi-square/Fisher's exact tests. Multivariable logistic regression models were built to assess baseline factors associated with initiation of canagliflozin versus DPP-4. RESULTS: Overall, 1,566 patients initiated canagliflozin, and 26,224 patients initiated DPP-4 treatment. Males constituted slightly more than 60% of each treatment group; mean age was approximately 55 years in each cohort. A significantly smaller proportion of canagliflozin patients (41.3%) initiated treatment with endocrinologists compared with DPP-4 patients (69.2%, P less than 0.001), and canagliflozin patients were more likely (29.4%) to initiate treatment with a primary care physician compared with DPP-4 patients (9.9%, P less than 0.001). Comorbidities were present more frequently in canagliflozin initiators: nephropathy (10.6% vs. 7.0%), retinopathy (10.4% vs. 7.5%), dyslipidemia (82.4% vs. 72.2%), and obesity (24.9% vs. 15.6%), respectively (P less than 0.001 for all comparisons). The mean (SD) Quan-Charlson Comorbidity Index score was greater for canagliflozin, 1.05 (1.7), compared with DPP-4 initiators, 0.92 (1.6), P = 0.002. Among the subset of patients with available hemoglobin A1c (A1c) results, a significantly smaller proportion of canagliflozin initiators (16.5%) versus DPP-4 initiators (26.7%) were at the A1c less than 7% treatment goal at baseline (P less than 0.001). Among patients with 3 months follow-up, 89.2% of canagliflozin and 75.1% of DPP-4 initiators had >= 1 fill for their index drugs over this time frame. Canagliflozin initiators had significantly greater baseline utilization of office visits, endocrinologist and outpatient services, and more prescription fills. Total diabetes-related medical costs at baseline ($3,025 vs. $3,477 for canagliflozin and DPP-4 initiators) were not significantly different, while mean diabetes-related pharmacy costs were higher in the canagliflozin group ($4,037 vs. $1,411, P less than 0.001). Regression analysis indicated that baseline insulin and glucagon-like peptide-1 use, as well as comorbid dyslipidemia and obesity, were significantly associated with the initiation of canagliflozin versus DPP-4 agents. CONCLUSIONS: In this sample of commercially insured patients within a large managed care plan, canagliflozin was often initiated as second- or third-line therapy, with a relatively high share of patients receiving concomitant antidiabetic injectables, compared with DPP-4 initiators. Canagliflozin initiators had highly elevated A1c levels and were frequently diagnosed with other metabolic conditions. Baseline pharmacy utilization and costs were higher among canagliflozin patients. Future research is needed to assess real-world clinical outcomes after canagliflozin initiation, while taking these baseline differences into account. PMID- 26679971 TI - Effects of High Doses of Vitamin C on Cancer Patients in Singapore: Nine Cases. AB - Introduction Intravenous high-dose vitamin C therapy is widely used in naturopathic and integrative oncology; however, a study reviewing its effects has never been performed in Singapore. This article serves to document administration of supportive vitamin C therapy for cancer patients in Singapore. METHODS: The clinical response of 9 cancer patients of differing stages to the regular administration of large doses (25-100 g/d) of intravenous vitamin C (IVC; ascorbic acid) is outlined. Tumor pathology and patient health were verified by doctors who do not practice vitamin C treatment. RESULTS: Cases suggesting survival beyond prognosis, improvement in quality of life, safe coadministration with and improved tolerance of conventional therapy, and deterioration in clinical condition following withdrawal of vitamin C therapy are documented clinically. Some patients experience the Jarisch-Herxheimer reaction-the release of endotoxin from microorganism death resulting in pimples, fever, and body odor for a few hours after the therapy, but these are resolved quickly with no lasting effects. CONCLUSION: Randomized trials of IVC therapy are recommended because it has minimal side effects and has shown promising results. PMID- 26679970 TI - Geographic Variation in Rosiglitazone Use Surrounding FDA Warnings in the Department of Veterans Affairs. AB - BACKGROUND: Geographic variation in the use of prescription drugs, particularly those deemed harmful by the FDA, may lead to variation in patient exposure to adverse drug events. One such drug is the glucose-lowering drug rosiglitazone, for which the FDA issued a safety alert on May 21, 2007, following the publication of a meta-analysis that suggested a 43% increase in the risk of myocardial infarction with the use of rosiglitazone. This alert was followed by a black box warning on August 14, 2007, that was updated 3 months later. While large declines have been documented in rosiglitazone use in clinical practice, little is known about how the use of rosiglitazone and other glucose-lowering drugs varied within the Department of Veterans Affairs (VA), surrounding the FDA alerts. Understanding this variation within integrated health care systems is essential to formulating policies that enhance patient protection and quality of care. OBJECTIVE: To document variation in the use of rosiglitazone and other glucose- lowering drugs across 21 Veterans Integrated Service Networks (VISNs). METHODS: We conducted a retrospective analysis of drug use patterns for all major diabetes drugs in a national cohort of 550,550 veterans with diabetes from 2003 to 2008. This included the time periods when rosiglitazone was added to (November 2003) and removed from (October 2007) the VA national formulary (VANF). We employed multivariable logistic regression models to statistically estimate the association between a patient's location and the patient's odds of using rosiglitazone. RESULTS: Aggregate rosiglitazone use increased monotonically from 7.7%, in the quarter it was added to the VANF (November 4, 2003), to a peak of 15.3% in the quarter when the FDA issued the safety alert. Rosiglitazone use decreased sharply afterwards, reaching 3.4% by the end of the study period (September 30, 2008). The use of pioglitazone, another glucose-lowering drug in the same class as rosiglitazone, was low when the FDA issued the safety alert (0.4%) but increased sharply afterwards, reaching 3.6% by the end of the study period. Insulin use increased monotonically; metformin use remained relatively flat; and sulfonylurea use exhibited a general declining trend throughout the study period. Statistically significant geographic variation was observed in rosiglitazone use throughout the study period. The prevalence range, defined as the range of minimum to maximum use across VISNs was 3.7%-12.4% in the first quarter (January 1 to March 31, 2003); 1.0%-5.5% in the last quarter of study period (July 1 to September 30, 2008); and reached a peak of 9.6%-25.5% in the quarter when the FDA safety alert was issued (April 1 to March 31, 2007). In 5 VISNs, peak rosiglitazone use occurred before the FDA issued the safety alert. The odds ratio of using rosiglitazone in a given VISN varied from 0.55 (95% CI = 0.52-0.59; VISN 10) to 1.58 (95% CI = 1.50-1.66; VISN 15), with VISN 1 being the reference region. The variation was higher in the periods after the FDA issued the safety alert. Much less variation was observed in the use of pioglitazone, metformin, sulfonylurea, and insulin. CONCLUSIONS: Our results show statistically significant variation in the way VISNs within the VA responded to the FDA alerts, suggesting a need for mechanisms that disseminate information and guidelines for drug use in a consistent and reliable manner. Further study of regions that adopted ideal practices earlier may provide lessons for regional leadership and practice culture within integrated health care systems. PMID- 26679972 TI - Boron uptake, localization, and speciation in marine brown algae. AB - In contrast to the generally boron-poor terrestrial environment, the concentration of boron in the marine environment is relatively high (0.4 mM) and while there has been extensive interest in its use as a surrogate of pH in paleoclimate studies in the context of climate change-related questions, the relatively depth independent, and the generally non-nutrient-like concentration profile of this element have led to boron being neglected as a potentially biologically relevant element in the ocean. Among the marine plant-like organisms the brown algae (Phaeophyta) are one of only five lineages of photosynthetic eukaryotes to have evolved complex multicellularity. Many of unusual and often unique features of brown algae are attributable to this singular evolutionary history. These adaptations are a reflection of the marine coastal environment which brown algae dominate in terms of biomass. Consequently, brown algae are of fundamental importance to oceanic ecology, geochemistry, and coastal industry. Our results indicate that boron is taken up by a facilitated diffusion mechanism against a considerable concentration gradient. Furthermore, in both Ectocarpus and Macrocystis some boron is most likely bound to cell wall constituent alginate and the photoassimilate mannitol located in sieve cells. Herein, we describe boron uptake, speciation, localization and possible biological function in two species of brown algae, Macrocystis pyrifera and Ectocarpus siliculosus. PMID- 26679973 TI - Multimorbidity, not a health condition or complexity by another name. PMID- 26679974 TI - A general practice perspective on early rheumatoid arthritis management: A qualitative study from Flanders. AB - BACKGROUND: General practitioners (GPs) may play a crucial role in early recognition, rapid referral and intensive treatment follow-up of patients with rheumatoid arthritis (RA). To improve early RA management, perceived barriers in general practice must be addressed. However, the general practice perspective on early RA management remains understudied. OBJECTIVE: To explore GPs' experiences, beliefs and attitudes regarding detection, referral, and intensive treatment for early RA. METHODS: In 2014, a qualitative study was conducted by means of individual, in depth, face-to-face interviews of a purposive sample of 13 Flemish GPs. Interviews were audio-recorded, transcribed verbatim and coded using the constant comparative method. RESULTS: GPs applied multiple assessment techniques for early RA detection and regularly prescribed non-steroidal anti-inflammatory drugs if they suspected early RA. However, GPs felt unconfident about their detection skills because early RA symptoms are often unclear, diagnostic tests could provide inconclusive results and the incidence is low in general practice. GPs mentioned various approaches and multiple factors determining their referral decision. Perceived referral barriers included limited availability of rheumatology services and long waiting times. GPs considered intensive treatment initiation to be the expertise of rheumatologists. Reported key barriers to intensive treatment included patients' resistance and non-adherence, lack of GP involvement and unsatisfactory collaboration with rheumatology services. CONCLUSION: GPs acknowledge the importance of an early and intensive treatment, but experience various barriers in the management of early RA. GPs should enhance their skills to detect early RA and should actively be involved in early RA care. PMID- 26679977 TI - Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Controlled Trial. AB - STUDY OBJECTIVE: We compare nasal inhalation of isopropyl alcohol versus placebo in treating nausea among emergency department (ED) patients. METHODS: A convenience sample of adults with chief complaints of nausea or vomiting was enrolled in a randomized, double-blind, placebo-controlled trial conducted in an urban tertiary care ED. Patients were randomized to nasally inhaled isopropyl alcohol versus nasally inhaled normal saline solution. Patient nausea and pain were measured with previously published 11-point verbal numeric response scale scores; patient satisfaction was measured by a 5-point Likert scale. The primary outcome was reduction in nausea 10 minutes poststart. Secondary outcomes included patient satisfaction and pain reduction measured at 10 minutes poststart. RESULTS: Of 84 recruited patients, 80 (95.2%) completed the study. Thirty-seven (46.3%) received nasally inhaled isopropyl alcohol and 43 (53.8%) received nasally inhaled normal saline solution. At 10 minutes postintervention, median nausea verbal numeric response scale score was 3 in the isopropyl alcohol arm versus 6 in the placebo arm, for an effect size of 3 (95% confidence interval 2 to 4). Median satisfaction score was 4 in the isopropyl alcohol arm versus 2 in the placebo arm, for an effect size of 2 (95% confidence interval 2 to 2). There were no significant differences between the 2 arms in median pain verbal numeric response scale scores or subsequent receipt of rescue antiemetics. CONCLUSION: We found that nasally inhaled isopropyl alcohol achieves increased nausea relief compared with placebo during a 10-minute period. PMID- 26679978 TI - Activation and Transformation of Ethane by Au2 VO3(+) Clusters with Closed-Shell Electronic Structures. AB - The study of chemical reactions between gold-containing heteronuclear oxide clusters and small molecules can provide molecular level mechanisms to understand the excellent activity of gold supported by metal oxides. While the promotion role of gold in alkane transformation was identified in the clusters with atomic oxygen radicals (O(-.)), the role of gold in the systems without O(-.) is not clear. By employing mass spectrometry and quantum chemistry calculations, the reactivity of Au2 VO3(+) clusters with closed-shell electronic structures toward ethane was explored. Both the dehydrogenation and ethene elimination channels were identified. It is gold rather than oxygen species initiating the C-H activation. The Au-Au dimer formed during the reactions plays important roles in ethane transformation. The reactivity comparison between Au2 VO3(+) and bare Au2(+) demonstrates that Au2 VO3(+) not only retains the property of bare Au2(+) that transforming ethane to dihydrogen, but also exhibits new functions in converting ethane to ethene, which reveals the importance of the composite system. This study provides a further understanding of the reactivity of metal oxide supported gold in alkane activation and transformation. PMID- 26679979 TI - Molecular taxonomy of Pseudapocryptes (Bleeker, 1874) mudskippers from Sundarban mangroves, India. AB - BACKGROUND: More than 40 species of mudskipper is recorded worldwide, but the molecular taxonomy of very few species is studied so far. OBJECTIVE: The objective of this study is to determine the molecular taxonomy and phylogenetic relationship of the Pseudapocryptes elongatus and Pseudapocryptes lanceolatus collected from the mudflats of Sundarban, India. METHODS: The mitochondrial COI gene was sequenced to analyze the molecular taxonomy. The species name associated with the present analyzed sequence as shown by BLAST searches of GenBank was used to define the phylogenetic relationship. RESULTS: Mitochondrial COI gene sequences of collected mudskippers were submitted to GenBank to get accession numbers. The BLAST search of GenBank matched 100% with the species name associated with the present analyzed sequence. CONCLUSIONS: The present study reveals the phylogenetic similarity between the species. PMID- 26679980 TI - Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki 67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus. AB - Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki 67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki 67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression. PMID- 26679982 TI - Hearing is believing: Birds learn fear. AB - Although it is known that animals attend to the vocalizations of others (referred to as eavesdropping), what has been missing, or at least left experimentally unproven, until now is whether animals can learn new associations between a signal and a threat. Here Magrath and colleagues (Current Biology, 25(15), 2047 2050, 2015) have for the first time conducted a field experiment that demonstrates just this: superb fairy-wrens learned to associate a novel vocalization with a predator. PMID- 26679981 TI - Histological structure of duodenum in gilts receiving low doses of zearalenone and deoxynivalenol in feed. AB - Deoxynivalenol (DON) and zearalenone (ZEN), produced by microfungi of the Fusarium family, are among the most commonly occurring mycotoxins. They are considered important factors affecting human and animal health as well as livestock productivity. The aim of this study was to determine the effect of low doses of these mycotoxins on the histological structure of the pig duodenum. The study was performed on 72 gilts, with initial weights of approximately 25kg, divided into 4 equal groups. Group I received per os ZEN (40MUg/kg BW), group II DON (12MUg/kg BW), group III-ZEN (40MUg/kg BW) and DON (12MUg/kg BW), and group IV-vehicle. The pigs were killed after 1, 2, 3, 4, 5 and 6 weeks of the treatment, and the duodenum samples were prepared for histological investigations. The slides were digitalized and subjected to morphometrical analysis. The treatment with DON and ZEN did not change the architecture of the mucosa or the ratio between goblet and adsorptive cells in the epithelium. The administration of DON induced an increase in the number of lymphocytes in the mucosal epithelium. Both mycotoxins, administered alone or together, increased the quantity of lymphocytes, plasma cells and macrophages with black-brown granules in the lamina propria. The time-courses of changes in the number of defense system cells evoked by DON and ZEN were different. In conclusion, dietary exposure to low doses of Fusarium mycotoxins should be considered an important risk factor for subclinical inflammation in the small intestine. PMID- 26679983 TI - Employing proteomics to unravel the molecular effects of antipsychotics and their role in schizophrenia. AB - Schizophrenia is an incurable neuropsychiatric disorder managed mostly by treatment of the patients with antipsychotics. However, the efficacy of these drugs has remained only low to moderate despite intensive research efforts since the early 1950s when chlorpromazine, the first antipsychotic, was synthesized. In addition, antipsychotic treatment can produce often undesired severe side effects in the patients and addressing these remains a large unmet clinical need. One of the reasons for the low effectiveness of these drugs is the limited knowledge about the molecular mechanisms of schizophrenia, which impairs the development of new and more effective treatments. Recently, proteomic studies of clinical and preclinical samples have identified changes in the levels of specific proteins in response to antipsychotic treatment, which have converged on molecular pathways such as cell communication and signaling, inflammation and cellular growth, and maintenance. The findings of these studies are summarized and discussed in this review and we suggest that this provides validation of proteomics as a useful tool for mining drug mechanisms of action and potentially for pinpointing novel molecular targets that may enable development of more effective medications. PMID- 26679985 TI - Corrigendum: Statistical Signs of Social Influence on Suicides. PMID- 26679984 TI - Vitreous floaters: Etiology, diagnostics, and management. AB - Vitreous is a hydrated extracellular matrix comprised primarily of water, collagens, and hyaluronan organized into a homogeneously transparent gel. Gel liquefaction results from molecular alterations with dissociation of collagen from hyaluronan and aggregation of collagen fibrils forming fibers that cause light scattering and hence symptomatic floaters, especially in myopia. With aging, gel liquefaction and weakened vitreoretinal adhesion result in posterior vitreous detachment, the most common cause of primary symptomatic floaters arising from the dense collagen matrix of the posterior vitreous cortex. Recent studies indicate that symptomatic floaters are not only more prevalent, but also have a negative impact on the quality of life that is greater than previously appreciated. We review the literature concerning management of symptomatic vitreous floaters, currently either with observation, vitrectomy, or Nd:YAG laser. Published evidence is consistent with a low-risk profile and excellent success rate for floater vitrectomy, particularly with sutureless small gauge instruments and a limited core vitrectomy without PVD induction. Nd:YAG laser treatment of floaters, reported less commonly, claims resolution of floaters ranging between 0% and 100%; however, both peer-reviewed literature and assertions on web-based nonpeer-reviewed laser vitreolysis sites remain to be substantiated, and at present only vitrectomy has proven value. Prospective studies using objective, quantitative outcome measures are required to assess the relative efficacy and safety of these two procedures as well as new therapies such as pharmacologic vitreolysis. PMID- 26679986 TI - BIOINFORMATICS, TISSUE DISTRIBUTION, AND SUBCELLULAR LOCALIZATION ANALYSES OF FK506 BINDING PROTEIN 12B FROM SILKWORMS. AB - FK506 binding proteins (FKBPs) are intracellular receptors of the immunosuppressant FK506 and play important roles in the correct folding of new proteins and the self-assembly of biological macromolecules. FKBP12 is a member of the FKBP family that is widely expressed and highly conserved in many species. In this study, we identified the complete cDNA sequence encoding the FKBP12 ortholog in Bombyx mori, named Bm-FKBP12B (GenBank accession no. DQ443423). Multiple-sequence alignment among different species revealed a high similarity among FKBP12 paralogs and orthologs. Bioinformatics analysis of the Bm-FKBP12B gene showed that it is located on chromosome 20 and consists of three exons and two introns. We cloned, expressed, and purified the Bm-FKBP12B protein in Escherichia coli and generated a specific polyclonal antibody against Bm-FKBP12B. The real-time quantitative reverse-transcription (qRT) PCR and Western blotting results showed that Bm-FKBP12B was present throughout all of the development stages, but it was abundant in the adult and embryo stages. Bm-FKBP12B expression was higher in the silk gland and gut, suggesting that it might play important roles in regulating gene expression in the silk gland and during silk fiber formation. Bm-FKBP12B protein was distributed in the cytoplasm, nucleus, and nuclear membrane. PMID- 26679989 TI - Porcine oocyte mtDNA copy number is high or low depending on the donor. AB - Oocyte capacity is relevant in understanding decreasing female fertility and in the use of assisted reproductive technologies in human and farm animals. Mitochondria are important to the development of a functionally good oocyte and the oocyte mtDNA copy number has been introduced as a useful parameter for prediction of oocyte competence. The aim of this study was to investigate: (i) if the oocyte donor has an influence on its oocyte's mtDNA copy number; and (ii) the relation between oocyte size and mtDNA copy number using pre- and postpubertal pig oocytes. Cumulus-oocyte complexes were collected from individual donor pigs. The oocytes were allocated into different size-groups, snap-frozen and single oocyte mtDNA copy number was estimated by quantitative real-time PCR using the genes ND1 and COX1. Results showed that mean mtDNA copy number in oocytes from any individual donor could be categorized as either 'high' (>=100,000) or 'low' (<100,000) with no difference in threshold between pre- and postpubertal oocytes. No linear correlation was detected between oocyte size and mtDNA copy number within pre- and postpubertal oocytes. This study demonstrates the importance of the oocyte donor in relation to oocyte mtDNA copy number, irrespectively of the donor's puberty status and the oocyte's growth stage. Observations from this study facilitate both further investigations of the importance of mtDNA copy number and the unravelling of relations between different mitochondrial parameters and oocyte competence. PMID- 26679990 TI - Chemotactic dynamics of catalytic dimer nanomotors. AB - Synthetic chemically powered nanomotors possessing the ability of chemotaxis are desirable for target cargo delivery and self-assembly. The chemotactic properties of a sphere dimer motor, composed of linked catalytic and inactive monomers, are studied in a gradient field of fuel. Particle-based simulation is carried out by means of hybrid molecular dynamics/multiparticle collision dynamics. The detailed tracking and motion analysis describing the running and tumbling of the sphere dimer motor in the process of chemotaxis are investigated. Physical factors affecting chemotactic velocity are discussed, and quantitative relations are presented. The influence of the geometry of sphere dimer motors on the chemotactic dynamics is explored, which is beneficial for the design of motors with high sensitivity for detecting the surrounding environment. PMID- 26679988 TI - Deformability of Tumor Cells versus Blood Cells. AB - The potential for circulating tumor cells (CTCs) to elucidate the process of cancer metastasis and inform clinical decision-making has made their isolation of great importance. However, CTCs are rare in the blood, and universal properties with which to identify them remain elusive. As technological advancements have made single-cell deformability measurements increasingly routine, the assessment of physical distinctions between tumor cells and blood cells may provide insight into the feasibility of deformability-based methods for identifying CTCs in patient blood. To this end, we present an initial study assessing deformability differences between tumor cells and blood cells, indicated by the length of time required for them to pass through a microfluidic constriction. Here, we demonstrate that deformability changes in tumor cells that have undergone phenotypic shifts are small compared to differences between tumor cell lines and blood cells. Additionally, in a syngeneic mouse tumor model, cells that are able to exit a tumor and enter circulation are not required to be more deformable than the cells that were first injected into the mouse. However, a limited study of metastatic prostate cancer patients provides evidence that some CTCs may be more mechanically similar to blood cells than to typical tumor cell lines. PMID- 26679991 TI - The effect of magnetic field on chiral transmission in p-n-p graphene junctions. AB - We investigate Klein tunneling in graphene heterojunctions under the influence of a perpendicular magnetic field via the non-equilibrium Green's function method. We find that the angular dependence of electron transmission is deflected sideways, resulting in the suppression of normally incident electrons and overall decrease in conductance. The off-normal symmetry axis of the transmission profile was analytically derived. Overall tunneling conductance decreases to almost zero regardless of the potential barrier height V0 when the magnetic field (B-field) exceeds a critical value, thus achieving effective confinement of Dirac fermions. The critical field occurs when the width of the magnetic field region matches the diameter of the cyclotron orbit. The potential barrier also induces distinct Fabry-Perot fringe patterns, with a "constriction region" of low transmission when V0 is close to the Fermi energy. Application of B-field deflects the Fabry Perot interference pattern to an off-normal angle. Thus, the conductance of the graphene heterojunctions can be sharply modulated by adjusting the B-field strength and the potential barrier height relative to the Fermi energy. PMID- 26679992 TI - Digital import of orbital implants to enhance navigation in reconstruction of the deep orbit. AB - Stereotactic navigation has become established in orbital surgery. It can assist in exploration and reconstruction by preventing plate positioning errors and ensuring adequate restoration of deep orbital anatomy. Pre-formed and custom-made implants have become increasingly popular with reliable outcomes in complex orbital reconstructions, but may require adjustment at the time of surgery. Planning for reconstruction can be improved by import of digital models of implants into the navigation system. This technique allows on-table confirmation of successful orbital reconstruction. PMID- 26679994 TI - In vivo degradation profile of porcine cartilage-derived extracellular matrix powder scaffolds using a non-invasive fluorescence imaging method. AB - We present a non-invasive fluorescence method for imaging of scaffold degradation in vivo by quantifying the degradation of porcine cartilage-derived extracellular matrix powder (PCP).Three-dimensional porous scaffolds should be biocompatible and bioresorbable, with a controllable degradation and resorption rate to match tissue growth. However, in vivo scaffold degradation and tissue ingrowth processes are not yet fully understood. Unfortunately, current analysis methods require animal sacrifice and scaffold destruction for the quantification of scaffold degradation and cannot monitor the situation in real time. In this study, Cy3, a fluorescent dye, was used for visualizing PCP and a real-time degradation profile was obtained quantitatively by a non-invasive method using an imaging system in which the reduction in fluorescence intensity depended on PCP scaffold degradation. Real-time PCP scaffold degradation was confirmed through changes in the volume and morphology of the scaffold using micro-computed tomography and microscopy. Our results suggest that extracellular matrix degradation was induced by collagen degradation because of the binding between Cy3 and collagen. This non-invasive real-time monitoring system for scaffold degradation will increase our understanding of in vivo matrix and/or scaffold degradation. PMID- 26679993 TI - Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex. AB - NMDA receptor (NMDAR) composition and synaptic retention represent pivotal features in the physiology and pathology of excitatory synapses. Here, we identify Rabphilin 3A (Rph3A) as a new GluN2A subunit-binding partner. Rph3A is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites. We find that Rph3A is enriched at dendritic spines. Protein-protein interaction assays reveals that Rph3A N terminal domain interacts with GluN2A(1349-1389) as well as with PSD-95(PDZ3) domains, creating a ternary complex. Rph3A silencing in neurons reduces the surface localization of synaptic GluN2A and NMDAR currents. Moreover, perturbing GluN2A/Rph3A interaction with interfering peptides in organotypic slices or in vivo induces a decrease of the amplitude of NMDAR-mediated currents and GluN2A density at dendritic spines. In conclusion, Rph3A interacts with GluN2A and PSD 95 forming a complex that regulates NMDARs stabilization at postsynaptic membranes. PMID- 26679995 TI - HIV-1 Vpr Protein Induces Proteasomal Degradation of Chromatin-associated Class I HDACs to Overcome Latent Infection of Macrophages. AB - Mechanisms underlying HIV-1 latency remain among the most crucial questions that need to be answered to adopt strategies for purging the latent viral reservoirs. Here we show that HIV-1 accessory protein Vpr induces depletion of class I HDACs, including HDAC1, 2, 3, and 8, to overcome latency in macrophages. We found that Vpr binds and depletes chromatin-associated class I HDACs through a VprBP dependent mechanism, with HDAC3 as the most affected class I HDAC. De novo expression of Vpr in infected macrophages induced depletion of HDAC1 and 3 on the HIV-1 LTR that was associated with hyperacetylation of histones on the HIV-1 LTR. As a result of hyperacetylation of histones on HIV-1 promotor, the virus established an active promotor and this contributed to the acute infection of macrophages. Collectively, HIV-1 Vpr down-regulates class I HDACs on chromatin to counteract latent infections of macrophages. PMID- 26679996 TI - Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity. AB - As an innate defense mechanism, macrophages produce reactive oxygen species that weaken pathogens and serve as secondary messengers involved in immune function. The Gram-negative bacterium Francisella tularensis utilizes its antioxidant armature to limit the host immune response, but the mechanism behind this suppression is not defined. Here we establish that F. tularensis limits Ca(2+) entry in macrophages, thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild type (live vaccine strain) or catalase deficient F. tularensis (DeltakatG) show distinct profiles in their H2O2 scavenging rates, 1 and 0.015 pm/s, respectively. Murine alveolar macrophages infected with DeltakatG display abnormally high basal intracellular Ca(2+) concentration that did not increase further in response to H2O2. Additionally, DeltakatG-infected macrophages displayed limited Ca(2+) influx in response to ionomycin, as a result of ionophore H2O2 sensitivity. Exogenously added H2O2 or H2O2 generated by DeltakatG likely oxidizes ionomycin and alters its ability to transport Ca(2+). Basal increases in cytosolic Ca(2+) and insensitivity to H2O2 mediated Ca(2+) entry in DeltakatG-infected cells are reversed by the Ca(2+) channel inhibitors 2-aminoethyl diphenylborinate and SKF-96365. 2-Aminoethyl diphenylborinate but not SKF-96365 abrogated DeltakatG-dependent increases in macrophage actin remodeling and IL-6 secretion, suggesting a role for H2O2 mediated Ca(2+) entry through the transient receptor potential melastatin 2 (TRPM2) channel in macrophages. Indeed, increases in basal Ca(2+), actin polymerization, and IL-6 production are reversed in TRPM2-null macrophages infected with DeltakatG. Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function. PMID- 26679997 TI - Pro-inflammatory Macrophages Sustain Pyruvate Oxidation through Pyruvate Dehydrogenase for the Synthesis of Itaconate and to Enable Cytokine Expression. AB - Upon stimulation with Th1 cytokines or bacterial lipopolysaccharides, resting macrophages shift their phenotype toward a pro-inflammatory state as part of the innate immune response. LPS-activated macrophages undergo profound metabolic changes to adapt to these new physiological requirements. One key step to mediate this metabolic adaptation is the stabilization of HIF1alpha, which leads to increased glycolysis and lactate release, as well as decreased oxygen consumption. HIF1 abundance can result in the induction of the gene encoding pyruvate dehydrogenase kinase 1 (PDK1), which inhibits pyruvate dehydrogenase (PDH) via phosphorylation. Therefore, it has been speculated that pyruvate oxidation through PDH is decreased in pro-inflammatory macrophages. However, to answer this open question, an in-depth analysis of this metabolic branching point was so far lacking. In this work, we applied stable isotope-assisted metabolomics techniques and demonstrate that pyruvate oxidation is maintained in mature pro inflammatory macrophages. Glucose-derived pyruvate is oxidized via PDH to generate citrate in the mitochondria. Citrate is used for the synthesis of the antimicrobial metabolite itaconate and for lipogenesis. An increased demand for these metabolites decreases citrate oxidation through the tricarboxylic acid cycle, whereas increased glutamine uptake serves to replenish the TCA cycle. Furthermore, we found that the PDH flux is maintained by unchanged PDK1 abundance, despite the presence of HIF1. By pharmacological intervention, we demonstrate that the PDH flux is an important node for M(LPS) macrophage activation. Therefore, PDH represents a metabolic intervention point that might become a research target for translational medicine to treat chronic inflammatory diseases. PMID- 26679999 TI - Type I Interferon Signaling Is Decoupled from Specific Receptor Orientation through Lenient Requirements of the Transmembrane Domain. AB - Type I interferons serve as the first line of defense against pathogen invasion. Binding of IFNs to its receptors, IFNAR1 and IFNAR2, is leading to activation of the IFN response. To determine whether structural perturbations observed during binding are propagated to the cytoplasmic domain, multiple mutations were introduced into the transmembrane helix and its surroundings. Insertion of one to five alanine residues near either the N or C terminus of the transmembrane domain (TMD) likely promotes a rotation of 100 degrees and a translation of 1.5 A per added residue. Surprisingly, the added alanines had little effect on the binding affinity of IFN to the cell surface receptors, STAT phosphorylation, or gene induction. Similarly, substitution of the juxtamembrane residues of the TMD with alanines, or replacement of the TMD of IFNAR1 with that of IFNAR2, did not affect IFN binding or activity. Finally, only the addition of 10 serine residues (but not 2 or 4) between the extracellular domain of IFNAR1 and the TMD had some effect on signaling. Bioinformatic analysis shows a correlation between high sequence conservation of TMDs of cytokine receptors and the ability to transmit structural signals. Sequence conservation near the TMD of IFNAR1 is low, suggesting limited functional importance for this region. Our results suggest that IFN binding to the extracellular domains of IFNAR1 and IFNAR2 promotes proximity between the intracellular domains and that differential signaling is a function of duration of activation and affinity of binding rather than specific conformational changes transmitted from the outside to the inside of the cell. PMID- 26679998 TI - Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis. AB - The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic down regulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for in vivo use. PMID- 26680000 TI - Structural Correlation of the Neck Coil with the Coiled-coil (CC1)-Forkhead associated (FHA) Tandem for Active Kinesin-3 KIF13A. AB - Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer. The reverse introduction of Pro-390 breaks the NC-CC1 coiled-coil dimer but provides the intrinsic flexibility to couple NC with the CC1-FHA tandem. Mutations of either NC, CC1, or the FHA domain all significantly impaired the motor activity. Thus, the three elements within the NC-CC1-FHA tandem of KIF13A are structurally interrelated to form a stable dimer for activating the motor. This work also provides the first direct structural evidence to support the formation of a coiled-coil neck by the short characteristic neck domain of kinesin-3. PMID- 26680002 TI - Reply. PMID- 26680001 TI - Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition. AB - Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis of mambalgin-1 and confirm the biological activity of the synthetic toxin both in vitro and in vivo. We also report the determination of its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, the functional domain by which the toxin inhibits ASIC1a channels was identified in its loop II and more precisely in the face containing Phe-27, Leu-32, and Leu-34 residues. Moreover, proximity between Leu-32 in mambalgin-1 and Phe-350 in rASIC1a was proposed from double mutant cycle analysis. These data provide information on the structure and on the pharmacophore for ASIC channel inhibition by mambalgins that could have therapeutic value against pain and probably other neurological disorders. PMID- 26680003 TI - Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission. AB - BACKGROUND: While unrelated bone marrow transplantation (UBMT) has been widely used as alternative donor transplantation, the use of umbilical cord blood transplantation (UCBT) is increasing recently. METHODS: We conducted a decision analysis to address which transplantation procedure should be prioritized for younger patients with acute myeloid leukemia (AML) harboring high- or intermediate-risk cytogenetics in first complete remission (CR1), when they lack a matched related donor but have immediate access to a suitable umbilical cord blood unit. Main sources for our analysis comprised the data from three phase III trials for a chemotherapy cohort (n = 907) and the registry data for a transplantation cohort (n = 752). RESULTS: The baseline analysis showed that when the 8/8 match was considered for UBMT, the expected 5-year survival rate was higher for UBMT than for UCBT (58.1% vs. 51.8%). This ranking did not change even when the 7/8 match was considered for UBMT. Sensitivity analysis showed consistent superiority of UBMT over UCBT when the time elapsed between CR1 and UBMT was varied within a plausible range of 3-9 months. CONCLUSIONS: These results suggest that 8/8 or 7/8 UBMT is a better transplantation option than UCBT even after allowing time required for donor coordination. PMID- 26680005 TI - Birth of fertile bimaternal offspring following intracytoplasmic injection of parthenogenetic haploid embryonic stem cells. PMID- 26680004 TI - Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer. AB - Both 5-methylcytosine (5mC) and its oxidized form 5-hydroxymethylcytosine (5hmC) have been proposed to be involved in tumorigenesis. Because the readout of the broadly used 5mC mapping method, bisulfite sequencing (BS-seq), is the sum of 5mC and 5hmC levels, the 5mC/5hmC patterns and relationship of these two modifications remain poorly understood. By profiling real 5mC (BS-seq corrected by Tet-assisted BS-seq, TAB-seq) and 5hmC (TAB-seq) levels simultaneously at single-nucleotide resolution, we here demonstrate that there is no global loss of 5mC in kidney tumors compared with matched normal tissues. Conversely, 5hmC was globally lost in virtually all kidney tumor tissues. The 5hmC level in tumor tissues is an independent prognostic marker for kidney cancer, with lower levels of 5hmC associated with shorter overall survival. Furthermore, we demonstrated that loss of 5hmC is linked to hypermethylation in tumors compared with matched normal tissues, particularly in gene body regions. Strikingly, gene body hypermethylation was significantly associated with silencing of the tumor-related genes. Downregulation of IDH1 was identified as a mechanism underlying 5hmC loss in kidney cancer. Restoring 5hmC levels attenuated the invasion capacity of tumor cells and suppressed tumor growth in a xenograft model. Collectively, our results demonstrate that loss of 5hmC is both a prognostic marker and an oncogenic event in kidney cancer by remodeling the DNA methylation pattern. PMID- 26680006 TI - Carbon neutrality: An ultimate goal towards sustainable wastewater treatment plants. PMID- 26680008 TI - Effects of a Sublethal and Transient Stress of the Endoplasmic Reticulum on the Mitochondrial Population. AB - Endoplasmic reticulum (ER) and mitochondria are not discrete intracellular organelles but establish close physical and functional interactions involved in several biological processes including mitochondrial bioenergetics, calcium homeostasis, lipid synthesis, and the regulation of apoptotic cell death pathways. As many cell types might face a transient and sublethal ER stress during their lifetime, it is thus likely that the adaptive UPR response might affect the mitochondrial population. The aim of this work was to study the putative effects of a non-lethal and transient endoplasmic reticulum stress on the mitochondrial population in HepG2 cells. The results show that thapsigargin and brefeldin A, used to induce a transient and sublethal ER stress, rapidly lead to the fragmentation of the mitochondrial network associated with a decrease in mitochondrial membrane potential, O2 (*-) production and less efficient respiration. These changes in mitochondrial function are transient and preceded by the phosphorylation of JNK. Inhibition of JNK activation by SP600125 prevents the decrease in O2 (*-) production and the mitochondrial network fragmentation observed in cells exposed to the ER stress but has no impact on the reduction of the mitochondrial membrane potential. In conclusion, our data show that a non lethal and transient ER stress triggers a rapid activation of JNK without inducing apoptosis, leading to the fragmentation of the mitochondrial network and a reduction of O2 (*-) production. J. Cell. Physiol. 231: 1913-1931, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26680007 TI - Tracking patterns of needs during a telephone follow-up programme for family caregivers of persons with stroke. AB - PURPOSE: Programmes that address stroke family caregiver needs and skill-building are recommended based on the literature and patient care guidelines for stroke rehabilitation. The purpose of this study was to explore patterns of perceived needs and skill-building during a stroke caregiver intervention programme. METHOD: Descriptive statistics were used to analyse data from 123 stroke caregivers enrolled in the intervention group of a randomised controlled clinical trial. Caregivers received eight weekly telephone sessions, with a booster session a month later. At each session, the Caregiver Needs and Concerns Checklist (CNCC) was used to identify and prioritise current needs that were then addressed through skill-building strategies. RESULTS: Perceived needs changed over time. Information about stroke was the highest priority need during Session 1. Managing survivor emotions and behaviours was the highest priority for Sessions 2 through 4. Caregivers generally waited until Sessions 5 through 9 to address their own emotional and physical health needs. Physical and instrumental care needs were relatively low but stable across all nine sessions. Skill building was consistently high, though it peaked during Sessions 2 and 3. CONCLUSIONS: Tracking patterns of needs and skill-building suggest appropriate timing for targeting different types of family caregiver support during stroke rehabilitation. Implications for Rehabilitation Family caregivers of stroke survivors play an essential role in the rehabilitation process of the stroke survivor. Identifying and addressing the priority needs and concerns of stroke caregivers during the early discharge period enables caregivers to provide sustained support for the stroke survivor. Rehabilitation professionals are in a key position to address evolving caregiver needs and concerns as they transition to home settings with follow-up care. PMID- 26680009 TI - Structural vs. functional mechanisms of duplicate gene loss following whole genome doubling. AB - BACKGROUND: The loss of duplicate genes - fractionation - after whole genome doubling (WGD) is the subject to a debate as to whether it proceeds gene by gene or through deletion of multi-gene chromosomal segments. RESULTS: WGD produces two copies of every chromosome, namely two identical copies of a sequence of genes. We assume deletion events excise a geometrically distributed number of consecutive genes with mean u >= 1, and these events can combine to produce single-copy runs of length l. If u = 1, the process is gene-by-gene. If u > 1, the process at least occasionally excises more than one gene at a time. In the latter case if deletions overlap, the later one simply extends the existing run of single-copy genes. We explore aspects of the predicted distribution of the lengths of single-copy regions analytically, but resort to simulations to show how observing run lengths l allows us to discriminate between the two hypotheses. CONCLUSIONS: Deletion run length distributions can discriminate between gene-by gene fractionation and deletion of segments of geometrically distributed length, even if u is only slightly larger than 1, as long as the genome is large enough and fractionation has not proceeded too far towards completion. PMID- 26680010 TI - Skin microbiome in melanomas and melanocytic nevi. AB - BACKGROUND: High-throughput DNA sequencing has shown that the cutaneous microbiome varies due to different exogenous and endogenous factors. OBJECTIVES: To characterize the microbiome of cutaneous melanomas and melanocytic nevi. MATERIAL AND METHODS: Non-invasive swab specimens were taken from 15 cutaneous melanomas and 17 benign melanocytic nevi. Partial sequencing of the 16S ribosomal RNA gene was carried out on the 454 GS-FLX Titanium platform and the resulting sequence data was analysed by bioinformatics and statistical methods. 95% of the OTUs (Operational Taxonomic Units) belonged to four phyla: Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes. The genus Propionibacterium was overall the most common genus, followed by Staphylococcus and Corynebacterium. Statistical analysis showed no significant differences in the relative abundances of bacterial genera or bacterial diversity between the patient groups. Melanoma samples showed a marginally decreased cutaneous microbial diversity. CONCLUSION: Our data suggests that the skin microbiome may not be a useful diagnostic tool for melanoma and melanocytic nevi. PMID- 26680011 TI - LENS: web-based lens for enrichment and network studies of human proteins. AB - BACKGROUND: Network analysis is a common approach for the study of genetic view of diseases and biological pathways. Typically, when a set of genes are identified to be of interest in relation to a disease, say through a genome wide association study (GWAS) or a different gene expression study, these genes are typically analyzed in the context of their protein-protein interaction (PPI) networks. Further analysis is carried out to compute the enrichment of known pathways and disease-associations in the network. Having tools for such analysis at the fingertips of biologists without the requirement for computer programming or curation of data would accelerate the characterization of genes of interest. Currently available tools do not integrate network and enrichment analysis and their visualizations, and most of them present results in formats not most conducive to human cognition. RESULTS: We developed the tool Lens for Enrichment and Network Studies of human proteins (LENS) that performs network and pathway and diseases enrichment analyses on genes of interest to users. The tool creates a visualization of the network, provides easy to read statistics on network connectivity, and displays Venn diagrams with statistical significance values of the network's association with drugs, diseases, pathways, and GWASs. We used the tool to analyze gene sets related to craniofacial development, autism, and schizophrenia. CONCLUSION: LENS is a web-based tool that does not require and download or plugins to use. The tool is free and does not require login for use, and is available at http://severus.dbmi.pitt.edu/LENS. PMID- 26680012 TI - Analysis of the solution conformations of T4 lysozyme by paramagnetic NMR spectroscopy. AB - A large number of crystal structures of bacteriophage T4 lysozyme (T4-L) have shown that it contains two subdomains, which can arrange in a compact conformation (closed state) or, in mutants of T4-L, more extended structures (open state). In solution, wild-type T4-L displays only a single set of nuclear magnetic resonance (NMR) signals, masking any conformational heterogeneity. To probe the conformational space of T4-L, we generated a site-specific lanthanide binding site by attaching 4-mercaptomethyl dipicolinic acid via a disulfide bond to Cys44 in the triple-mutant C54T/C97A/S44C of T4-L and measured pseudocontact shifts (PCS) and magnetically induced residual dipolar couplings (RDC). The data indicate that, in solution and in the absence of substrate, the structure of T4-L is on average more open than suggested by the closed conformation of the crystal structure of wild-type T4-L. A slightly improved fit was obtained by assuming a population-weighted two-state model involving an even more open conformation and the closed state, but paramagnetic relaxation enhancements measured with Gd(3+) argue against such a conformational equilibrium. The fit could not be improved by including a third conformation picked from the hundreds of crystal structures available for T4-L mutants. PMID- 26680013 TI - A clinical method for mapping and quantifying blood stasis in the left ventricle. AB - In patients at risk of intraventrcular thrombosis, the benefits of chronic anticoagulation therapy need to be balanced with the pro-hemorrhagic effects of therapy. Blood stasis in the cardiac chambers is a recognized risk factor for intracardiac thrombosis and potential cardiogenic embolic events. In this work, we present a novel flow image-based method to assess the location and extent of intraventricular stasis regions inside the left ventricle (LV) by digital processing flow-velocity images obtained either by phase-contrast magnetic resonance (PCMR) or 2D color-Doppler velocimetry (echo-CDV). This approach is based on quantifying the distribution of the blood Residence Time (TR) from time resolved blood velocity fields in the LV. We tested the new method in illustrative examples of normal hearts, patients with dilated cardiomyopathy and one patient before and after the implantation of a left ventricular assist device (LVAD). The method allowed us to assess in-vivo the location and extent of the stasis regions in the LV. Original metrics were developed to integrate flow properties into simple scalars suitable for a robust and personalized assessment of the risk of thrombosis. From a clinical perspective, this work introduces the new paradigm that quantitative flow dynamics can provide the basis to obtain subclinical markers of intraventricular thrombosis risk. The early prediction of LV blood stasis may result in decrease strokes by appropriate use of anticoagulant therapy for the purpose of primary and secondary prevention. It may also have a significant impact on LVAD device design and operation set-up. PMID- 26680014 TI - Sensitivity of lumbar spine loading to anatomical parameters. AB - Musculoskeletal simulations of lumbar spine loading rely on a geometrical representation of the anatomy. However, this data has an inherent inaccuracy. This study evaluates the influence of defined geometrical parameters on lumbar spine loading utilising five parametrised musculoskeletal lumbar spine models for four different postures. The influence of the dimensions of vertebral body, disc, posterior parts of the vertebrae as well as the curvature of the lumbar spine was studied. Additionally, simulations with combinations of selected parameters were conducted. Changes in L4/L5 resultant joint force were used as outcome variable. Variations of the vertebral body height, disc height, transverse process width and the curvature of the lumbar spine were the most influential. These parameters can be easily acquired from X-rays and should be used to morph a musculoskeletal lumbar spine model for subject-specific approaches with respect to bone geometry. Furthermore, the model was very sensitive to uncommon configurations and therefore, it is advised that stiffness properties of discs and ligaments should be individualised. PMID- 26680016 TI - Relationship between Social-Emotional and Neurodevelopment of 2-Year-Old Children with Congenital Heart Disease. AB - OBJECTIVE: The purpose of this study was to describe social-emotional outcomes and the relationship with neurodevelopmental outcomes in a cohort of 2-year-old children who underwent surgery for congenital heart disease (CHD) in infancy, and explore the relationship between the outcomes and parental and surgical factors. DESIGN: A two-center prospective cross-sectional cohort study. PATIENTS: A cohort of 105 2-year-olds who underwent surgery in infancy for severe CHD MEASURES: Social-emotional and neurodevelopment was evaluated with the Infant and Toddler Social and Emotional Assessment tool (ITSEA), and the Bayley Scales of Infant Toddler Development, Third Edition. RESULTS: Neurodevelopment was delayed in the CHD cohort with significantly worse results compared to published Australian based norms in all domains (P < .001) and in the Cognitive (P < .001) and Language (P < .001) domains with respect to the reported American norms. Social emotional outcome was similar to Australian norms in all domains but better than the American based norms in the Internalizing domain (P < .05). Higher maternal education was associated to better neurodevelopmental outcome in all domains and better scores in the internalizing and externalizing domains of the ITSEA. There was a moderate correlation (r = 0.43, P < .001) between Language and social emotional competence. Motor development was influenced by the need for a significant cardiac reoperation. CONCLUSIONS: The influences of social factors may be underestimated in the outcome of children with CHD. Language development in those with CHD may be improved with intervention targeting social-emotional competence; further research is needed in this area. PMID- 26680017 TI - Transcriptomic analysis suggests a key role for SQUAMOSA PROMOTER BINDING PROTEIN LIKE, NAC and YUCCA genes in the heteroblastic development of the temperate rainforest tree Gevuina avellana (Proteaceae). AB - Heteroblasty, the temporal development of the meristem, can produce diverse leaf shapes within a plant. Gevuina avellana, a tree from the South American temperate rainforest shows strong heteroblasty affecting leaf shape, transitioning from juvenile simple leaves to highly pinnate adult leaves. Light availability within the forest canopy also modulates its leaf size and complexity. Here we studied how the interaction between the light environment and the heteroblastic progression of leaves is coordinated in this species. We used RNA-seq on the Illumina platform to compare the range of transcriptional responses in leaf primordia of G. avellana at different heteroblastic stages and growing under different light environments. We found a steady up-regulation of SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL), NAC, YUCCA and AGAMOUS-LIKE genes associated with increases in age, leaf complexity, and light availability. In contrast, expression of TCP, TPR and KNOTTED1 homeobox genes showed a sustained down regulation. Additionally, genes involved in auxin synthesis/transport and jasmonate activity were differentially expressed, indicating an active regulation of processes controlled by these hormones. Our large-scale transcriptional analysis of the leaf primordia of G. avellana sheds light on the integration of internal and external cues during heteroblastic development in this species. PMID- 26680019 TI - The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease. AB - Mineral metabolism disturbances are common in chronic kidney disease (CKD) and have been classified as a new clinical entity, also known as CKD-mineral and bone disorders (CKD-MBD). A decrease in the bone strength, whose clinical manifestation is a tendency for fracture, has been recognized as an important component of CKD-MBD. Because of ethical issues, measurements of the bone strength in the human body are usually limited to noninvasive techniques, such as radiography, dual-energy X-ray absorptiometry and the assays of bone turnover biomarkers. However, it has been postulated recently that the evidence concerning bone strength based solely on the determination of the bone quantity may be insufficient and that bone quality should also be examined. In this regard, an animal model of CKD can represent an experimental tool to test the effectiveness of new therapeutic strategies. Despite the many available methods that are used to diagnose metabolic bone disorders and predict fracture risk especially in small rodents with CKD, it turns out that the most appropriate are biomechanical tests, which can provide information about the structural and material properties of bone. The present review summarizes and discusses the principles for carrying out selected biomechanical tests (3-point bending test and compression test) and their application in clinical practice. PMID- 26680018 TI - Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women. AB - Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer. PMID- 26680020 TI - Health care professionals' views of the factors influencing the decision to refer patients to a stroke rehabilitation trial. AB - BACKGROUND: Effective recruitment is an essential element of successful research but notoriously difficult to achieve. This article examines health care professionals' views on the factors influencing decision-making regarding referral to a stroke rehabilitation trial. METHODS: Semi-structured interviews and a card-sorting task were undertaken with stroke service staff in acute and community hospital trusts. Data analysis used a thematic framework approach. RESULTS: Twenty-seven qualified health care professionals from 12 (6 acute and 6 community) hospital trusts and one charity participated. Four main factors emerged: patient-related, professional views, the organisation and research logistics, which all contributed to staff's decision about whether to refer patients to a trial. Clinicians identified patient-related factors as the most frequent influence and considered themselves the patients' advocate. They used their knowledge of the patient to anticipate the patients' reaction to possible participation and tended to only refer those whom they perceived would respond positively. Participants also identified experience of research, a sense of ownership of the project and a positive view of the intervention being evaluated as factors influencing referral. The need to prioritise clinical matters, meet managerial demands and cope with constant change were organisational factors impacting negatively on referral. Staff often simply forgot about recruitment in the face of other higher priorities. Quick, simple, flexible research processes that were closely aligned with existing ways of working were felt to facilitate recruitment. CONCLUSIONS: Patient- and professional-related factors were the most frequent influence on clinicians' recruitment decisions, which often had a 'gate keeping' effect. Managerial and clinical responsibility to juggle multiple (often higher) priorities was also an important factor. To facilitate recruitment, researchers need to develop strategies to approach potential participants as directly as possible to enable them to make their own decisions about participation; ensure that research processes are as quick and simple as possible; align with existing clinical pathways and systems; and give regular reminders and ongoing support to promote recruitment. TRIAL REGISTRATION: ISRCTN, 98287938 . Registered 6 May 2015. PMID- 26680021 TI - Relationship of plasma cell-free DNA level with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever. AB - Crimean-Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell-free DNA (pcf-DNA) is a novel marker indicating cellular damage. So far, the role of pcf-DNA did not investigate in CCHF patients. In the current study, pcf DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf-DNA level, virus load, and disease severity. Seventy-two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf-DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf-DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf-DNA levels in mild, intermediate, and severe patient groups was significant. The pcf-DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non-survivors had higher pcf-DNA levels at admission (P = 0.001). A direct relationship was found between the pcf-DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf-DNA level of 0.42 as the optimal cut-off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf-DNA levels may be used as a biomarker in predicting CHHF prognosis. PMID- 26680022 TI - MethGo: a comprehensive tool for analyzing whole-genome bisulfite sequencing data. AB - BACKGROUND: DNA methylation is a major epigenetic modification regulating several biological processes. A standard approach to measure DNA methylation is bisulfite sequencing (BS-Seq). BS-Seq couples bisulfite conversion of DNA with next generation sequencing to profile genome-wide DNA methylation at single base resolution. The analysis of BS-Seq data involves the use of customized aligners for mapping bisulfite converted reads and the bioinformatic pipelines for downstream data analysis. RESULTS: Here we developed MethGo, a software tool designed for the analysis of data from whole-genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS). MethGo provides both genomic and epigenomic analyses including: 1) coverage distribution of each cytosine; 2) global cytosine methylation level; 3) cytosine methylation level distribution; 4) cytosine methylation level of genomic elements; 5) chromosome wide cytosine methylation level distribution; 6) Gene-centric cytosine methylation level; 7) cytosine methylation levels at transcription factor binding sites (TFBSs); 8) single nucleotide polymorphism (SNP) calling, and 9) copy number variation (CNV) calling. CONCLUSIONS: MethGo is a simple and effective tool for the analysis of BS-Seq data including both WGBS and RRBS. It contains 9 analyses in 5 major modules to profile (epi)genome. It profiles genome-wide DNA methylation in global and in gene level scale. It can also analyze the methylation pattern around the transcription factor binding sites, and assess genetic variations such as SNPs and CNVs. MethGo is coded in Python and is publically available at http://paoyangchen-laboratory.github.io/methgo/. PMID- 26680023 TI - Emergency medicine: this is what we do. PMID- 26680015 TI - Systems Proteomics View of the Endogenous Human Claudin Protein Family. AB - Claudins are the major transmembrane protein components of tight junctions in human endothelia and epithelia. Tissue-specific expression of claudin members suggests that this protein family is not only essential for sustaining the role of tight junctions in cell permeability control but also vital in organizing cell contact signaling by protein-protein interactions. How this protein family is collectively processed and regulated is key to understanding the role of junctional proteins in preserving cell identity and tissue integrity. The focus of this review is to first provide a brief overview of the functional context, on the basis of the extensive body of claudin biology research that has been thoroughly reviewed, for endogenous human claudin members and then ascertain existing and future proteomics techniques that may be applicable to systematically characterizing the chemical forms and interacting protein partners of this protein family in human. The ability to elucidate claudin-based signaling networks may provide new insight into cell development and differentiation programs that are crucial to tissue stability and manipulation. PMID- 26680024 TI - Traumatic cardiac arrest: central venous cannulation under direct vision following rescue thoracotomy. PMID- 26680025 TI - Barriers to focused echocardiography education. PMID- 26680026 TI - Clinical interventions by helicopter emergency medical service teams: Time for key performance indicators? PMID- 26680027 TI - Troponin use in Emergency Department syncope. PMID- 26680028 TI - Reproductive characteristics of women diagnosed with premature ovarian insufficiency. AB - In this retrospective cohort study (n = 479), the proportion of women with premature ovarian insufficiency (POI) who conceived was assessed, the reproductive characteristics of women with POI who had previously been pregnant or had never been pregnant compared, and the interval between last conception and the menopause in women with POI who had become pregnant assessed. Time to pregnancy and maternal age at first childbirth were compared between women with POI and population-based controls (n = 2304). Women with POI who had previously been pregnant (n = 249 [52%]) experienced menopause at a later age compared with controls (35.0 years: interquartile range [IQR] 32.0-37.5 versus 30.0 years [IQR 23.0-35.0]; P < 0.001). The median interval between last conception and menopause in the former group was 4.0 years (IQR 1.0-8.0). Time to pregnancy did not differ between women with POI and controls. Women with POI were younger at first childbirth compared with controls (27.3 years [IQR 23.4-30.5] versus 29.2 years [26.4-32.0]; P < 0.001). The reproductive capacity of young women with POI is comparable to women in the general population, up until a given age; thereafter a rapid loss of the potential to conceive occurs. PMID- 26680029 TI - Healthcare information technology in medical education - a forgotten focus. PMID- 26680030 TI - Teledermatology in medical education - a 'rash' decision? PMID- 26680032 TI - A systematic review of clinical practice guidelines and best practice statements for the diagnosis and management of varicocele in children and adolescents. AB - A systematic review was conducted to identify and qualitatively analyze the methods as well as recommendations of Clinical Practice Guidelines (CPG) and Best Practice Statements (BPS) concerning varicocele in the pediatric and adolescent population. An electronic search was performed with the MEDLINE, EMBASE, Science Direct, and Scielo databases, as well as guidelines' Web sites until September 2015. Four guidelines were included in the qualitative synthesis. In general, the recommendations provided by the CPG/BPS were consistent despite the existence of some gaps across the studies. The guidelines issued by the American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) did not provide evidence-based levels for the recommendations given. Most of the recommendations given by the European Association of Urology (EAU) and European Society of Pediatric Urology (ESPU) were derived from nonrandomized clinical trials, retrospective studies, and expert opinion. Among all CPG/BPS, only one was specifically designed for the pediatric population. The studied guidelines did not undertake independent cost-effectiveness and risk-benefit analysis. The main objectives of these guidelines were to translate the best evidence into practice and provide a framework of standardized care while maintaining clinical autonomy and physician judgment. However, the limitations identified in the CPG/BPS for the diagnosis and management of varicocele in children and adolescents indicate ample opportunities for research and future incorporation of higher quality standards in patient care. PMID- 26680034 TI - The 9th Congress of The Andalusian Society of Organ and Tissue Transplantation (SATOT). PMID- 26680031 TI - Major regulatory mechanisms involved in sperm motility. AB - The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies. PMID- 26680033 TI - Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis. AB - The objective of this systemic review was to evaluate the benefit of repairing clinical varicocele in infertile men with nonobstructive azoospermia (NOA). The surgically obtained sperm retrieval rate (SRR) and pregnancy rates following assisted reproductive technology (ART) with the use of retrieved testicular sperm were the primary outcomes. The secondary outcomes included the presence of viable sperm in postoperative ejaculate to avoid the testicular sperm retrieval and pregnancy rates (both assisted and unassisted) using postoperative ejaculated sperm. An electronic search to collect the data was performed using the MEDLINE and EMBASE databases until April 2015. Eighteen studies were included in this systematic review and accounted for 468 patients who were diagnosed with NOA and varicocele. These patients were subjected to either surgical varicocele repair or percutaneous embolization. Three controlled studies evaluating sperm retrieval outcomes indicated that in patients who underwent varicocelectomy, SRR increased compared to those without varicocele repair (OR: 2.65; 95% CI: 1.69-4.14; P< 0.001). Although pregnancy rates with the use of testicular sperm favored the varicocelectomy group, results were not statistically significant (clinical pregnancy rate OR: 2.07; 95% CI: 0.92-4.65; P= 0.08; live birth rate OR: 2.19; 95% CI: 0.99-4.83; P= 0.05). The remaining fifteen studies reported postoperative semen analysis results. In 43.9% of the patients (range: 20.8%-55.0%), sperm were found in postoperative ejaculates. Pregnancy rates for unassisted and assisted (after IVF/ICSI) were 13.6% and 18.9% in the group of men with sperm in postoperative ejaculates, respectively. Our findings indicate that varicocelectomy in patients with NOA and clinical varicocele is associated with improved SRR. In addition, approximately 44% of the treated men will have enough sperm in the ejaculate to avoid sperm retrieval. Limited data on pregnancy outcomes with both postoperative ejaculated sperm and harvested testicular sperm preclude any firm conclusion with regard to the possible increased fertility potential in treated individuals. In conclusion, the results of our study indicate that infertile men with NOA and clinical varicocele benefit from varicocelectomy. Given the low/moderate quality of evidence available, it is advisable that doctors discuss with their patients with NOA the risks and benefits of varicocele repair. PMID- 26680035 TI - Severe Supratentorial Intracerebral Hemorrhage: Factors Related to Brain Death Development. AB - OBJECTIVE: This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). METHODS: A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score <= 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. RESULTS: A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P = .003), anticoagulant therapy (OR, 3.561; P = .050), presence of photomotor impairment at admission (OR, 7.095; P = .001), rebleeding after supratentorial ICH (OR, 5.613; P = .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P = .001). CONCLUSIONS: Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors. PMID- 26680036 TI - Non-Heart-Beating Donor Program: Results After 3 Years of Experience. AB - BACKGROUND: Non-heart-beating donation (NHBD) is a useful way to obtain organs and tissues. Therefore, since 2012 we have had an NHBD protocol in the metropolitan area of Seville. The aim of this work was to present the results obtained after 3 years of program. METHODS: Prospective observational study carried out from 2012 to 2014. We included all patients with an extrahospitalary sudden death who did not survive despite cardiopulmonary resuscitation, becoming a potential donors (PD). Variables included number of consultations, PD, allowed donor (AD), real donor (RD), and family or legal refusals; minutes of out hospital care, in-hospital care, cannulation, and perfusion of the RD; and number of organs and tissues removed and viable proportion. Nonallowed donors were grouped according to the discarding cause. RESULTS: We received 97 consultations, of which 40 were performed as PD. Of these, 24 were AD (60%) and 22 RD (55%). There were only 2 family refusals. In 2012, 10 patients were donors, 5 in 2013, and 7 in 2014. The out-hospital median time was 71 (interquartile range [IQR] 60 76) minutes, in-hospital 29 (26-34) minutes, cannulation 28 (24-33) minutes, and perfusion 135 (105-177) minutes. Eighteen tissues and 43 organs were extracted, of which 32 were implanted (75%), with kidneys (96%) being more frequent. Nonallowed donors numbered 12 in 2012, 4 in 2013, and 1 in 2014, and out-hospital causes were the most frequent discard reason. CONCLUSIONS: NHBD is a useful program in our city with a low refusal rate (8%), an average of 1.45 organs per donor, and kidney the most frequent organ. PMID- 26680037 TI - Donation in Private Clinics as an Alternate Strategy to Increase the Pool of Donors. AB - In recent years, the donation process is being characterized by a decreased number of brain deaths and a logistical shift toward cardiac-death donation, both controlled and uncontrolled, in Spain. As we know, cardiac-death donors produce fewer usable organs than brain-death donors. Therefore, many of the Spanish transplant coordinators are working to find new strategies that bring efficiency to donor detection. Since 2012, at the Virgen del Rocio University Hospital, Seville, we have been trying to obtain more donors with the use of a huge logistical and administrative effort of all the elements that make up the donation and transplantation teams, because we have sought to get organ donors in all private clinics in the city. The result of this effort has succeeded in increasing the donation rate in Seville to 3 donors and >6 usable organs per year. This paper also analyzes the characteristics of these donors, comparing our results with our community and the country. The conclusion of all this, we believe, encourages persevering in those efforts and endorses a strategy that could be applied in other parts of the world with good results in terms of transplanted organs. PMID- 26680038 TI - Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program. AB - BACKGROUND: Donors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010 2014). METHODS: We compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. RESULTS: DCD were more frequently men from the A blood group who were younger (48.9 +/- 11 vs 55.2 +/- 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 +/- 11 vs 53.5 +/- 13 years old for DBD, P = .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1(st) and 3(rd) years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n = 445), 86% vs 92% (P = .02) in the third year, but were similar to DBD from age 50 to 59 (n = 407) and higher than DBD over age 60 (n = 636), 80% at the 3(rd) year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3(rd) year, P = .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. CONCLUSIONS: With the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present. PMID- 26680039 TI - Dominicans Resident in Spain and the United States Faced With Deceased Organ Donation. AB - BACKGROUND: Investigating the attitude of subgroups of populations living in different countries is useful for establishing whether there are differences in opinion in terms of place of residence. The objective of the study was to analyze attitudes toward deceased organ donation in the population from the Dominican Republic who are residing in the southeast of the United States and Spain. METHODS: A sample was taken of residents of the population from the Dominican Republic residing in Florida (the United States) (n = 63) and in Spain (n = 80), which was stratified by age and sex. A validated questionnaire about psychosocial aspects (PCID-DTO Rios) was self-administered and completed anonymously: the chi(2) test, Student t test, and logistic regression analysis were used. RESULTS: The completion rate was 86% (123 respondents of the 143 selected). Of those surveyed, 54% were in favor, 23% were against, and 23% were undecided. Of the residents in Spain (n = 57) 63% (n = 36) were in favor, 12% (n = 7) were against, and 25% (n = 14) were undecided. Of the residents in the United States (n = 66) 46% (n = 30) were in favor, 33% (n = 22) were against, and 21% (n = 14) were undecided (P < .001). The following factors were found to be associated with attitude: 1) level of education [OR = 12.195 (52.631-2.808); P = .001]; 2) concern about the possible mutilation of the body after donation [OR = 11.363 (47.619-2.695; P = .001]; and 3) rejection of cremation or burial of the body after death [OR = 6.134 (21.276-1.763); P = .004]. CONCLUSIONS: Attitude toward the donation of the respondent's own deceased organs after death was more favorable among Dominican residents in Spain compared with those living in the United States. PMID- 26680040 TI - Brain Death: Is It a Misunderstood Concept Among Nursing Students in the South of Poland? AB - BACKGROUND: The objective of the present study was to analyze the knowledge and acceptance of the brain death (BD) concept among nursing students. METHODS: The study was undertaken in the academic year of 2011 to 2012 in nursing students from the University of the South of Poland. The sample was carried out in compulsory sessions, in the 5 years of the nursing degree study, with a completion rate of 80%. The questionnaire was validated (PCID-DTO Rios), self administered, and completed anonymously. RESULTS: The completion rate was 93% (492 of 530). Of the students surveyed, 75% (n = 369) knew the concept of BD and considered it to mean a person's death. Of the rest, 19% (n = 93) did not know it, and the remaining 6% (n = 30) believed that it did not mean that a person was dead. The following variables were significantly related with the correct knowledge of the BD concept: 1) age (22 +/- 2 years; P <= .001); 2) academic year (P <= .001); 3) discussion with friends about organ donation and transplantation (ODT) (P = .035); 4) partner's favorable attitude toward donation and transplantation (P = .009); and 5) being Catholic (P = .031). In the multivariate analysis, the following variables persisted as independent variables related to the BD concept: a) age [OR = 1.468 (1.247-1.697); P <= .001] and b) partner's opinion of ODT [OR = 2.248 (1.255-4.025); P = .006]. No association was found with attitude toward ODT. CONCLUSIONS: More than 25% of the students from the Jagiellonian University of Krakow did not know or accept the concept of brain death. PMID- 26680041 TI - What Do Future Nursing Professionals Believe About Living Donor Kidney Transplantation? An Analysis of Attitudes of Nursing Students of the Medical University of Poznan in Western Poland. AB - BACKGROUND: Living donor kidney transplantation (LDKT) is the best treatment option in the late stage of chronic kidney disease. The objective of the study was to analyze the attitudes of nursing students at the Medical University of Poznan toward living donation of kidney. METHODS: Sampling points were compulsory attendance in the 5 nursing courses of the degree of fulfilment of 80%. The validated questionnaire (PCID-DVR Rios) was self-administered and anonymous. RESULTS: The completion rate was 92% (324 of 354). Among the students, 91% (n = 296) were in favor of LDKT, 5% (n = 15) were undecided, and 4% (n = 11) remained is against. When the living kidney donor is not related, 57% (n = 185) of respondents were in favor. The factors that are associated with a more favourable attitude are 1) the needs of organs for transplantation are covered (P = .012); 2) attitude in favor of organ donation and transplantation (P <= .001); 3) attitude toward living liver donation (P = .001); 4) attitude in favor of acceptance of LDKT for a relative (P <= .001); 5) discussing organ donation and transplantation with friends (P = .002); and 6) attitude in favor of organ donation from a family member (P = .011). In the multivariate analysis, highlights are acceptance of the donation of a living kidney donor from a family member [OR = 9.900 (35.714-2.770); P <= .001] and donating a piece of liver in life [OR = 50 (166.666-14.492); P <=.001]. CONCLUSIONS: Among the nursing students, 91% are in favor of living kidney donation. PMID- 26680042 TI - Impact of Asystolic Donations in Kidney Transplant Activity From Cadaveric Donors in Andalusia. AB - BACKGROUND: Kidneys from donors after brain death (DBD) cannot meet the demand for renal transplants in Andalusia. METHODS: We analyzed the impact of using non heart-beating donors (NHBD) in Andalusia from the start of this program to the present. RESULTS: From 2010 to 2014, brain-death kidney donations remained at a standstill (1,635 in total) although NHBD increased from 2.4% to 16% annually, to 5% of the total (n = 164: 83 type II Maastricht [NHBD-T2] and 81 type III Maastricht [NHBD-T3]). The donors were more frequently men (T2 80.5% and T3 76.5% vs DBD 58.2%; P < .001). NHBD were younger (48.9 +/- 10.8 y vs DBD 53.3 +/- 16 y; P < .001); 11.6% of NHBD were >60 and 0% >70 years old, versus 39.4% and 15.2% of DBD, respectively; this is mostly explained by NHBD-T2 (48.9 +/- 10.8 y vs DBD 53.3 +/- 16 y). NHBD were used much less frequently than DBD in recipients over the age of 65 years or for retransplanted or hyperimmunized patients and never on priority recipients (children and combined transplant patients). Blood groups differed significantly among different donor types (A, O, B, AB): NHBD-T2 65.1%, 27.7%, 7.2%, and 0%, respectively; NHBD-T3 45.7%, 45.7%, 8.6%, and 0%; and DBD 46.5%, 39.4%, 10.2 %, and 3.9% (P = .01). The immediate output of the graft also differed in the proportion of primary nonfunction and delayed graft function: NHBD-T2 9.8% and 70.7%, respectively; NHBD-T3 5.0% and 65.0%; and DBD 5.9% and 28.7%. CONCLUSIONS: The development of an NHBD program allows us to maintain and even increase transplants in our region. The impact on transplant access for O group recipients without priority will depend on the type of NHBD (low proportion of O group in NHBD-T2). PMID- 26680043 TI - Opinion of Nursing Students of the University of Bydgoszcz in Poland About the Transplantation of Living Liver Donors. AB - INTRODUCTION: Liver transplantation from living liver donation (LLD) has become an important source of liver grafts. MATERIAL AND METHOD: We studied the 2011 2012 academic year attitude of nursing students from a university in Poland. The sampling points were compulsory attendance in the 5 nursing courses. The validated questionnaire was Project Collaborative International Donor-Living Liver Donation Rios. The questionnaire was completed anonymously and was self administered. RESULTS: The completion rate was 89% (440 of 495); 91% (n = 398) were in favor of the related LLD, 8% (n = 37) were undecided, and 1% (n = 5) were against. When the attitude toward LLD is not related, 40% (n = 177) of respondents were in favor. The favorable attitude was associated with the following: consideration of the needs of organs for transplantations are covered (P <= .001); attitude in favor toward organ donation and transplantation (ODT) (P = .001); attitude in favor toward LLD (P = .007); attitude in favor of the acceptance of a LLD by a family member (P = .001); discussion of ODT with the family (P <= .001); being in favor of donating organs of a relative (P <= .001); and being Catholic (P = .003). After multivariate analysis, we observed the following significant correlations: the thought that the needs of transplantation organs are covered (odds ratio [OR] = 4.608; P = .020); being ready to accept a liver from a LLD (OR = 3.125; P = .038); discussion with the family about the subject of donation and transplantation (OR = 3.215; P = .003); and not belonging to any doctrine or religious belief (OR = 11.363; P = .039). CONCLUSIONS: In this study 91% of nursing students were in favor of living organ donation. PMID- 26680044 TI - Factors Affecting Attitude Toward Organ Donation Among Nursing Students in Warsaw, Poland. AB - BACKGROUND: The opinion of future nursing professionals can influence the number of transplants. The objective of this study was to analyze the attitude of nursing students at the Medical University of Warsaw in the center of Poland toward organ donation and determine the factors that affect this attitude. METHODS: The study was conducted in the 2011 to 2012 academic year. The study population consisted of nursing students. Type of sampling consisted of sampling in points of compulsory attendance, in the 5 nursing courses with the higher degree of fulfillment of 80%. Measuring instrument used was the validated questionnaire (PCID-DTO Rios). The questionnaire was completed anonymously and was self-administered. RESULTS: The completion rate was 96% (793 of 828). Of the students surveyed (n = 793), 69% (n = 547) were in favor of organ donation and transplantation, 25% (n = 201) were undecided, and 6% (n = 45) were against. This attitude was related to being in favor of donating the organs of a relative (OR = 3.174; P < .001); discussion of the subject with the family (OR = 2.188; P < .001); positive attitude toward donation and transplantation of the father (OR = 3.039; P = .001); considered to having good information on the subject (OR = 8.695; P < .001); being a regular donor blood (OR = 3.597; P = .001); not worried by the possible mutilation of the body after donation (OR = 6.802; P < .001); and accepting other treatment options of the body such as the burial (OR = 1.683; P = .015). CONCLUSIONS: More than 30% of the nursing students are not in favor of organ donation, but this attitude is conditioned by several psychosocial factors. PMID- 26680045 TI - Attitude of Nursing Students at the University of Lublin in Poland Toward Xenotransplantation of Organs. AB - OBJECTIVE: Because of the shortage of organs, it has become necessary to look for alternative sources of organs, such as xenotransplantation. The aim of this study was to analyze the attitude of nursing students at a university in the Eastern Poland toward xenotransplantation, to determine factors that affect their acceptance. MATERIAL AND METHOD: During the 2011-2012 academic year, nursing students at the University of the Eastern Poland enrolled the 5 nursing courses self-administered a validated questionnaire (the PCID-XenoTx Rios) anonymously. We undertook a descriptive statistical analysis using the Student t test, chi(2) test, and logistic regression analysis. RESULTS: The completion rate was 90% (608 of 672). When asked about the acceptability of organ donation from humans, 62% (n = 379) were in favor, 9% (n = 54) against, and 29% (n = 175) undecided. We found a significant association between the acceptability of transplantation and the university course and the respondents' religion (P <= .05). Fourth-year students have a more favorable attitude toward xenotransplantation than third-year students (75% vs 54%; P = .018). Catholics accept this type of donation more readily than those belonging to other faith traditions (63% vs 37%; P = .053). In the multivariate analysis, academic course is a significant influence on attitude toward xenotransplantation (odds ratio, 2.421; 95% CI, 4.347-1.345; P = .003). CONCLUSIONS: Nursing students have an unfavorable attitude toward xenotransplantation. This attitude is influenced by the religious beliefs and their academic year. PMID- 26680046 TI - Attitudes Toward Living Donation in the Bolivian Population Residing in Spain. AB - INTRODUCTION: Living donation is increasingly necessary to address the shortage of organs for transplantation. Analyzing attitudes and influences toward living donation is essential. This study sought to analyze the attitude toward living donation in the population of Bolivians residing in Spain, and the variables that influence their attitude. MATERIAL AND METHODS: We selected a sample of Bolivians living in Spain. Respondents were selected using a stratified sampling by age and sex. We used a validated questionnaire of psychosocial aspects (the questionnaire of Proyecto Colaborativo Internacional Donante about Living Kidney Donation [Donacion de Vivo Renal in Spanish]), which is self-administered and anonymous. The Student t test, chi(2), and Fisher tests, as well as logistic regression analysis, were used to analyze the gathered data. RESULTS: Of all respondents (n = 206), 83% (n = 170) were in favor of living-related donation, and 32% (n = 66) were in favor of living-unrelated donation. The rest, 8.5% (n = 18) were not in favor of living donation and 8.5% (n = 18) were undecided. Acceptance of the living donation was associated with the religious beliefs of the respondent (P = .014), with no worry about the scars that may remain after the donation (P = .016), and with the risk evaluation of living donation (P = .029). On multivariate analysis, the most important variable was the risk associated with living donation (odds ratio, 6.329; 95% CI, 30.303-1.328; P = .021). CONCLUSIONS: Attitudes toward living donation among the Bolivian population residing in Spain is favorable, and represents a group that may be encouraged to become donors. PMID- 26680047 TI - Involvement of Religious Factors on the Attitude Toward Organs Donation Among the Ecuadorian Population Resident in Spain. AB - INTRODUCTION: The attitude toward cadaveric organ donation is modulated by different factors, such as religious beliefs. This study sought to analyze the attitude of nationals of Ecuador resident in Spain regarding deceased organ donation depending on their religious beliefs. MATERIAL AND METHODS: A sample of Ecuadorian population resident in Spain (n = 461) stratified by age and sex was selected. We used a validated questionnaire of psychosocial aspects (PCID-DTO Rios), which is self-administered and anonymous. The chi(2) test, Student t test, and logistic regression analysis were used to analyze data. RESULTS: Of the 461 survey respondents, 86% (n = 395) were Catholic, 7% (n = 31) were believers of other faiths, and 7% (n = 35) declared themselves agnostic or atheist. A significant association between the religious beliefs and attitude toward organ donation among those tested can be objectified: 61% of Catholics (n = 241), 42% of believers in non-Catholic doctrines (n = 13), and 49% of atheists/agnostics (n = 17) were in favor of donation (P = .05). Among religious people, 77% of respondents believed their religion was favorable toward donation and 35%, although in favor of organ cadaveric donation, consider their religion contrary to donation (P < .001). CONCLUSIONS: The attitude toward cadaveric organ donation among the Ecuadorian population resident in Spain is influenced by religious beliefs and considers what their religion says regarding organ donation. PMID- 26680048 TI - Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study. AB - INTRODUCTION: It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. OBJECTIVE: The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. PATIENTS AND METHODS: The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). RESULTS: Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD 6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. CONCLUSIONS: eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available. PMID- 26680049 TI - Analysis of Pregnancy-Induced Anti-HLA Antibodies Using Luminex Platform. AB - BACKGROUND: The impact of pregnancy on the incidence of HLA sensitization is poorly explored, and most of the data were obtained by use of a complement dependent cytotoxicity (CDC) assay with an incidence of 18% to 30%. In many cases, antibodies cannot be detected by CDC as their level fades in time. However, this state of "latent" sensitization can still have a significant clinical impact in a subsequent transplantation setting. METHODS: Pregnancy induced HLA sensitization was analyzed in 69 mothers without a history of transfusions or transplants. The mothers and their offspring were typed for HLA A, HLA-B, and HLA-DR. Sera from the mothers were studied using the Luminex screening test to detect anti-HLA class I and class II antibodies. Positive and borderline sera were further analyzed using single antigen kits. RESULTS: Thirty four sera (49.3%) were positive in the screening test (52.9% for class I and 61.7% for class II antibodies). All of them tested positive for paternal alloantigens by single antigen. Positive paternal alloantigens were also detected in 52.9% of class I and 36.3% of class II sera with borderline screening. Interestingly, in a further analysis, the mean of the MFIs of paternal alloantigens that resulted negative was calculated and compared with that of neutral alloantigens and that of maternal self-antigens; in both cases, differences were highly significant (288 vs 153, P < .0001; 288 vs 102, P < .0001; respectively). CONCLUSIONS: This study shows a high incidence of pregnancy induced HLA sensitization and suggests that HLA typing of partners of women who have been pregnant may contribute to a better risk assessment in the transplantation setting. PMID- 26680050 TI - Impact of Early Low-Grade Proteinuria and Allograft Dysfunction on Survival in Expanded Criteria Donor Kidney Transplant Recipients. AB - INTRODUCTION: Recent studies have demonstrated a relationship between low-grade proteinuria and worse graft survival, but this has not been fully studied in expanded criteria donor (ECD) kidney transplant recipients. AIM: The aim of this study was to assess whether the combination of early low-grade proteinuria (<1 g/d) and allograft dysfunction at the third month post-transplantation predicts outcomes in terms of survival in ECD kidney transplant recipients. MATERIAL AND METHODS: We studied a cohort of 269 ECD kidney transplant recipients subdivided into 4 groups according to clinically relevant proteinuria (300 mg/d) and median creatinine (Cr; 1.7 mg/dL; interquartile range, 1.4-2.1 mg/dL) at the third month post-transplantation: Group A (Cr <1.7 mg/dL and proteinuria <300 mg/24 h; n = 97), Group B (Cr <1.7 mg/dL and proteinuria >=300 mg/24 h; n = 38), Group C (Cr >=1.7 mg/dL and proteinuria <300 mg/24 h; n = 79), and Group D (Cr >=1.7 mg/dL and proteinuria >=300 mg/24 h; n = 55). RESULTS: Death-censored graft survival was significantly lower in Group D compared with the rest (P < .007). Multivariate Cox regression analysis using fixed covariates showed that the combination of low-grade proteinuria and a lower estimated glomerular filtration rate (eGFR) as associated with graft failure (hazard rate [HR] 2.5, 95% confidence interval [CI], 1.09-5.97; P = .03). CONCLUSIONS: The early association of low-grade proteinuria and allograft dysfunction represents an important risk factor for graft loss in ECD kidney transplant recipients. Strategies to optimize renal function could improve the outcome in this specific population. PMID- 26680051 TI - Graft Survival in Patients With Polycystic Kidney Disease With Nephrectomy of Native Kidney Pretransplant. AB - INTRODUCTION: Autosomal-dominant polycystic disease (ADPKD) represents 5%-10% of cases of end-stage renal failure. However, management of these patients in terms of whether or not to perform a transplant and optimal timing remains controversial. The objective of our analysis was to evaluate graft survival in patients with ADPKD in which we conduct pretransplant nephrectomy. METHODS: This retrospective study including renal transplant patients secondary to ADPKD in our hospital between January 2000 and December 2012. Pretransplant native kidney nephrectomy was indicated in cases of need for space or repeated complications (cysts). We compared the initial function and graft survival between groups of transplanted based on whether nephrectomy had been performed or not. RESULTS: Eighty-seven patients underwent a kidney transplant owing to ADPKD; 62% (n = 54) were male, with an average age of 55.22 years. Twenty-seven patients (30%) underwent nephrectomy native kidneys before transplantation. There were no serious postoperative complications. Patients who underwent nephrectomy (group 1) showed values of creatinine of 1.57 and 1.50 mg/dL at 3 and 6 months, respectively. In the no nephrectomy group, these values were 2.03 and 1.83 mg/dL, respectively. Graft survival after the first year was of 98% for group 1 and 95% for group 2. The 5-year implant survival was 95% and 80%, respectively. CONCLUSIONS: Native kidney nephrectomy before transplantation in ADPKD is safe in an experienced center, both in terms of surgery-related morbidity and mortality and graft survival and function. PMID- 26680052 TI - Incidence and Long-Term Prognosis of Cancer After Kidney Transplantation. AB - BACKGROUND: Malignancy is an important cause of mortality in renal transplants recipients. The incidence of cancer is increased by immunosuppressive treatment and longer kidney graft survival. The aim of this study was to evaluate the incidence, prognosis and survival of posttransplant malignancies: solid organ cancer (SOC), posttransplant lymphoproliferative disorder (PTLD), and nonmelanoma skin cancer (NMSC). METHODS: We retrospectively studied the development of cancers among kidney transplants patients in our hospital from January 1979 to January 2015. We analyzed demographic and clinical characteristics, risk factors, and patient survival after tumor diagnosis. RESULTS: We included 1450 kidney transplants recipients with a mean follow-up was 10 years; among them, 194 developed malignancies. The mean age at presentation was 59 +/- 10 years. The SOC, PTLD, and NMSC incidences were 6.2%, 1.2%, and 6%, respectively. The most common tumors were kidney (16.6%), colon (11%), bladder (10%), breast (10%), prostate (10%), and lung (8.8%). The median times to development of a SOC, PTLD, and NMSC were 6.86 (range, 3.7-12), 4.43 (range, 1.8-5.7), and 8.19 (range, 3.8 12.2) years, respectively. Risk factors associated with developing SOC and PTLD were patient age (odds ratio [OR], 1.03; P < .001) and time posttransplant (OR, 1.05; P = .02), whereas for NMSC were to be male (OR, 3.61; P < .001), to take calcineurin inhibitors (OR, 2.17; P = .034), patient age (OR, 1.05; P < .001) and time posttransplant (OR, 1.15; P < .01). The mean survival time from the diagnosis of SOC, PTLD, and NMSC were 2.09 (range, 0.1-5.3), 0.22 (range, 0.05 1.9), and 7.68 (range, 3.9-10.5) years, respectively (P < .001). CONCLUSIONS: SOC occurs more frequently than other malignancies among renal transplant patients. NMSC has better survival and prognosis. Older patients and prolonged graft function have a greater risk of developing malignancies. PMID- 26680053 TI - Treatment With Darbepoetin During the First Year After Renal Transplantation: The Starting Point. AB - INTRODUCTION: Multiple factors are associated with post-transplantation anemia, and renal function is the main factor. The aims of this study were to compare the evolution of hemoglobin in the first year post-transplantation according to darbepoetin (DA) treatment, and factors related to it, to evaluate the difference between earlier versus delayed treatment, and to describe the dose change pattern. PATIENTS AND METHODS: We describe a retrospective study of cohorts in 462 transplant recipients (2004-2011). The variables reported were from donor, transplantation recipient, and DA treatment. RESULTS: In this study, 67.5% of patients were treated with DA, 32.5% were not. The comparison of hemoglobin in both groups during the first year showed a similar evolution with significant differences between consecutive measures until the second trimester. The hemoglobin of the treated group was significantly lower. The evolution of renal function was not different. Multivariate analysis related DA treatment to delayed graft function (DGF) and albuminuria in the first year. Patients with early versus delayed DA introduction did not show a difference regarding length of treatment, but the total dose in the delayed introduction was lower. The evolution of creatinine and hemoglobin was similar in both groups. CONCLUSION: The introduction of DA was related to DGF and albuminuria. The delayed introduction of DA meant the following: less total dose than earlier introduction, no difference in length of treatment, and a similar evolution in hemoglobin and renal function in both groups. The lack of guidelines about DA treatment in renal transplantation makes it difficult to establish a pattern of dose adjustment. PMID- 26680054 TI - Development of Donor-Specific Anti-HLA Antibodies After Restarting Hemodialysis Due to Graft Failure. AB - BACKGROUND: Incidents of renal replacement therapy (RRT) from renal transplants are on the rise. Some authors have associated the development of donor-specific anti-HLA antibodies (DSA) with the end of immunosuppression treatment (IS) and/or the performing of a transplantectomy. The objective of this study was to analyze the characteristics of transplant patients having high immunological risk who restarted RRT and the subsequent development of DSA. METHODS: We selected incidents on RRT carried out between 1980 and 2012 in our center: 146 cases; they presented non-DSA cytotoxic antibodies prior to returning to RRT. Survival time for the graft was 77.2 months; the average follow-up period for DSA development was 131.9 months. DSA in 76 cases (52.1%). Of 146 grafts, 72 underwent transplantectomy and 41 presented DSA after returning to RRT. In 17 of these cases (41.5%), the development of DSA occurred prior to the transplantectomy. Fifty-one cases of DSA were registered at the date of completion of the IS treatment, and 40 appeared after discontinuation (median 36 weeks) and 11 with previous appearance. IS was completed, with a median of 13 weeks after the return to RRT. RESULTS: No association was found between DSA development and order of graft, transplantectomy, or premature loss of the graft (<=15 months) after the return to RRT. There were significant differences between the number of HLA incompatibilities of the donor and the development of DSA. CONCLUSIONS: The development of DSA in high-immunological risk patients after restarting RRT is not related to transplantectomy. PMID- 26680055 TI - Role of Transarterial Chemoembolization to Downstage Hepatocellular Carcinoma Within the Milan Criteria. AB - The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplantation centers. We present our results using transarterial chemoembolization (TACE) as a neo-adjuvant treatment in our center between 2002 and 2013 to determine its effectiveness in downstaging (DS) HCC within the Milan criteria (MC). Clinical variables were recorded of both donors and recipients, such as diagnosis and treatment, variables related to its etiology, the use of TACE as a neo-adjuvant treatment, immunosuppressive therapy, toxicity, recurrence of disease, exitus, and others. Sixty-four patients were analyzed. Median age was 57 (range, 51-64) years. In this study, 84% (54) were male and 16% (10) were women. Etiology of HCC was viral in 47% (30), alcoholic in 25% (16), and other in 28% (18). TACE was conducted in 45 patients (70%). Every patient included in our study presented a T2 stage (of tumor-nodes-metastasis [TNM]) before surgery, thus within the MC. However, DS protocol was performed in 5 patients (7.8%). We performed a bivariate analysis, having assessed that the use of TACE decreases T2 stage into T1-T0 stage (P < .05). We have also calculated the recurrence-free survival, which reaches up to 80% to 125 months. Furthermore, even though the statistical differences are not consistent due to the simple size presented, we conclude that TACE is a safe and effective therapy to control HCC progression during the waiting list time. PMID- 26680056 TI - Preoperative Cardiac Assessment of Patients Undergoing Orthotopic Liver Transplantation: Experience in One Center. AB - Preoperative cardiac evaluation of patients undergoing liver transplantation is not well established. Stress testing is used in many centers, and clinical guidelines suggest its use. However, the specificity and sensibility of stress echocardiography to predict coronary lesions have been very low in some studies. Moreover, it has a low positive predictive value to predict complications after liver transplantation. We retrospectively analyzed 143 patients who underwent liver transplantation in our center and report our experience in the use of stress echocardiography. We describe cardiac complications during and after liver transplantation. Low prevalence of ischemic heart disease in asymptomatic patients undergoing liver transplantation make stress testing useless in risk stratification because it has a low positive predictive value. So the risk stratification of these patients before liver transplant surgery remains a challenge. PMID- 26680057 TI - Influence of Waiting List in Recurrence Disease of Hepatocellular Carcinoma. AB - BACKGROUND: We describe the results of our liver transplantation (LT) patients for hepatocellular carcinoma (HCC) in 2004 to 2012 to determine the differences on the basis of time on the waiting list to establish the risk of recurrence of liver disease. METHODS: Clinical variables were recorded for both donors and recipients as well as variables of diagnosis, the use of transarterial chemoembolization during the waiting list time (WLT), complications, re transplantation, and exitus. Fifty-eight patients were analyzed. Mean age was 57 +/- 8 years (men, 83%; 48 patients). Viral etiology of HCC was 50% (n = 29); alcoholic, 26% (n = 15); and others, 24% (n = 14). RESULTS: Exitus was established in 24 patients (41%); only 5 patients (7%) were attributable to HCC. In the cohort of patients with less than 6 months of WLT, we registered both higher rates of downstaging protocols (10.7% vs 7.5%) and tumor size (3 cm vs 2 cm) compared with the other group. Bivariate studies were conducted according to the WLT (WLT <6 months, WLT >=6 months), finding differences in recurrence of liver disease (P < .05). This fact was confirmed after a binary logistic regression. CONCLUSIONS: Our results in a subgroup of less than 6 months of WLT included patients with increased tumor size or presentation of multiple nodes, with a worse prognosis and therefore to be prioritized in the treatment of LT. Therefore, in our population there is a significant risk of tumor recurrence in patients with less WLT for LT, but it cannot be overestimated to all type of patients with HCC. PMID- 26680058 TI - Comparison of Two Types of Liquid Biopsies in Patients With Hepatocellular Carcinoma Awaiting Orthotopic Liver Transplantation. AB - INTRODUCTION: Orthotopic liver transplantation (OLT) is considered one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). It has been shown that more than 10% of transplanted individuals suffer relapse during the first year after surgery and most of them die because of the tumor. The circulating tumor cells (CTCs) are the main source of recurrences as they disseminate from a primary or metastatic tumor lesion through peripheral blood. We aimed to determine the concentration of CTCs in peripheral blood in these patients by 2 different approaches: the CellSearch and the IsoFlux systems to assess their applicability to this disease monitoring. PATIENTS AND METHODS: A comparative study was conducted in 21 patients with HCC eligible for liver transplantation according to the Milan criteria, whose peripheral blood was processed by the CellSearch and the IsoFlux systems. RESULTS: CTCs were isolated in 1 of the 21 patients (4.7%) by the CellSearch system and in 19 of the 21 patients (90.5%) by the IsoFlux method. The comparison of both methods using Bland-Altman plot shows that there is not consistency in the determination of CTCs in our patients, finding a proportional bias between them. CONCLUSION: The results obtained by both CTCs isolation systems are not interchangeable nor transferable. The CellSearch system does not seem to be the ideal approach for studying CTCs in patients with HCC. The IsoFlux system displays greater sensitivity in the identification of CTCs and might become an important tool in patient management. PMID- 26680059 TI - Outcomes of Liver Transplantation During Adulthood After Kasai Portoenterostomy Due to Biliary Atresia. AB - Biliary atresia (BA) is a neonatal progressive cholangiopathy of unknown etiology and one of the most common reasons for liver transplantation (LT) in children. Kasai portoenterostomy (KP) improves survival of the native liver, although LT remains the only ultimate treatment. In some cases KP makes it possible to defer the ultimate LT until adulthood. We report our experience regarding 5 cases of BA treated with LT during adulthood. KP was performed in all patients at an average age of 176 days (range, 60-280), which allowed an average survival of the native liver of 19.01 years (range, 14.06-22.32). Five-year survival rate was 100%. Ten year survival rate did not reach 100% because of a death 9.55 years after LT due to chronic graft rejection, in a patient who was already prepared for a new LT. Our results corroborate that KP remains the first-line treatment of BA. Early performance of the KP provides children with the best chance of survival, allowing the delay of the LT to adulthood. LT during adulthood in these patients achieves good post-LT survival rate; we have not found any data regarding this group of patients in the literature. PMID- 26680060 TI - Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years. AB - We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts. PMID- 26680061 TI - Cerebral Hemodynamics Patterns by Transcranial Doppler in Patients With Acute Liver Failure. AB - INTRODUCTION: About half of patients with acute liver failure (ALF) show clinical signs of cerebral edema and intracranial hypertension. Neuroimaging diagnostics and electroencephalography have poor correlation with intracranial pressure measurement. OBJECTIVE: The objective of this study was to characterize the cerebral hemodynamics patterns with transcranial Doppler (TCD) sonography in patients with ALF. METHOD: We studied 21 patients diagnosed with ALF, admitted to the intensive care unit (ICU) at the Centro de Investigaciones Medico Quirurgicas of Cuba. All of these patients had a TCD performed on arrival at ICU, evaluating the following: systolic (SV), diastolic (DV), and medium (MV) flows velocities and pulsatility index (PI) in right middle cerebral artery (RMCA) via temporal windows. RESULTS: The sonographic patterns of cerebral hemodynamics were as follows: low-flow, 12 patients (57.1%); high resistance, 5 patients (23.8%); and hyperemic, 4 patients (19%). Patients who died while waiting had lower MV RMCA (56.1 vs 58.1 cm/s) and higher PI (1.71 vs 1.41) than patients who could undergo transplantation (P = .800 and P = .787, respectively). CONCLUSIONS: In patients diagnosed with ALF admitted to the ICU the predominating cerebral hemodynamic pattern was low-flow with resistance increase. The TCD was shown to be a useful tool in the initial evaluation for prognosis and treatment. PMID- 26680062 TI - Complications Associated With Liver Transplantation in Recipients With Body Mass Index >35 kg/m(2): Would It Be a Poor Prognosis Predictive Factor? AB - BACKGROUND: Obesity is a global epidemic that continues to increase in a great number of countries, and it has become a major public health problem in Spain. Unfortunately, the impact of obesity on survival in liver transplantation (LT) recipients is underestimated and controversial. The aim of this study was to determine if obesity is a risk factor for morbidity and mortality after LT. METHODS: In a retrospective cohort study of the records of 180 consecutive patients who had undergone to LT from 2007 to 2013, 11 obese patients with body mass index (BMI) >35 kg/m(2) were identified. Their data have been compared with recipients with BMI 20-25 kg/m(2). RESULTS: There were no differences in demographic data, Child-Pugh score, Model for End-Stage Liver Disease score, or cause of liver failure. BMI >35 kg/m(2) recipients had a significantly higher rate of portal vein thrombosis before LT, compared with the BMI 20-25 kg/m(2) group (36.5% vs 13.9%; P = .041). There were also no differences in development of post-reperfusion syndrome. The groups were also comparable concerning morbidity rate after LT, stay in the intensive care unit, and global hospital stay. However, the mortality rate was significantly higher in the obese group compared with the nonobese group (72.7% vs 38.9%; P = .032). CONCLUSIONS: The results of the study clearly demonstrate higher mortality rates in obese patients undergoing LT; thus, it is fair to consider obesity as a poor prognosis predictive factor concerning mortality rate. PMID- 26680063 TI - Technique Resource for Difficult Auricular Anastomosis in Lung Transplantation. AB - OBJECTIVES: Atrial anastomosis in lung transplantation (LT) can present significant technical difficulties, especially when there is a very posterior left inferior pulmonary vein, in donor-recipient disproportion or excessive separation of the receptor's pulmonary veins owing to atrial dilatation; hence, its implementation requires excessive heart handling and longer ischemia time, which result in increased perioperative complications. This technique, which uses the recipient's superior pulmonary vein, avoids these problems, although it is not applicable in all cases because no pressure gradient at the suture level is required. Therefore, the suture diameter must be equal or greater than the sum of both graft pulmonary veins diameters. METHODS: This retrospective study recorded the age/gender (donor and recipient), preoperative morbidity, type of surgery, perioperative, vascular complications, mortality, and postoperative stay. Descriptive and inferential statistical study was made by SPSS. RESULTS: We performed 82 LTs between January 2009 and June 2012, 18 with the new technique (14 men/4 women; 52 +/- 15 years). There were 14 single lung and 4 double lung transplants. The new technique does not increase the ischemic times when compared with the classic technique. No vascular dehiscence, fistulas, or thrombosis were found. There were observed fewer vascular complications (P = .042). Early mortality was presented in 4 cases (22.2%). CONCLUSIONS: This new technique achieves the objectives described (no increases in ischemic time, fewer vascular complications). However, an absolute confirmation requires a study comparing similar technical LT given that the new resource was only used in highly complex procedures. PMID- 26680064 TI - Evolution and Risk Factors for Early Mortality After Lung Transplantation for Idiopathic Pulmonary Fibrosis: An Experience of 20 Years. AB - High early mortality after lung transplantation (LT) for idiopathic pulmonary fibrosis (IPF) is still not well controlled, and some aspects remain debated. The aim of this study was to evaluate our experience to identify factors that might improve the early outcomes. Among the 427 patients transplanted from October 1993 to December 2014, 117 IPF patients underwent LT at our department. There was an increasing age of transplant recipients, and the overall early (1-mo_ mortality was 25/117 (21.4%) with a progressive decrease over the years. Logistic regression analysis for early mortality was performed, and multivariate analysis identified recipient age <55 years (P = .042; odds ratio [OR], 2.98), single-lung transplants (P = .001; OR, 5.226), and previous corticosteroid treatment (P = .05; OR, 5.128) as independent risk factors for development of early mortality. In conclusion, despite the increasing age of transplant recipients, we observed a decrease in mortality to almost one-half compared with our initial results. According to our results, the mortality risk in patients <55 years old is independent from the type of transplant (single or double), being higher with a single transplant. In addition, corticosteroid treatment should be reduced to achieve lower early mortality. PMID- 26680065 TI - Analysis of the Incidence of Noncutaneous Neoplasia After Lung Transplantation and Its Impact on Prognosis. AB - INTRODUCTION: Increased survival in lung transplant recipients, the need for immunosuppressive therapy, and many risk factors before and after transplantation enhance the development of malignancies. This study sought to analyze the incidence of noncutaneous tumors after lung transplantation in our hospital, the risk factors for malignancy, and its impact on prognosis. PATIENTS AND METHODS: A retrospective analysis of clinical records of patients after lung transplantation in our hospital from October 1993 to December 2014. RESULTS: The study population included 443 patients. In total, 35 neoplasia developed in 33 patients (9.6%). Twelve cases were posttransplant lymphoproliferative disorders (PTLDs), 7 localized in the native lung, 7 gynecologic neoplasia (2 in the breast, 4 in the vulva, and 1 in the cervix), 3 in the colon, 2 in the nervous system (one was an astrocytoma), 2 in the prostate, 1 in the kidney, and 1 in the esophagus. The average time between transplantation and malignancy detection was 52.7 +/- 45.4 months, being earlier in patients with PTLDs than in non-PTLD. Eleven patients who developed malignancy (all patients with neoplasia in native lung and in cervix, 1 in the colon, 1 PTLD, and 1 in the nervous system) died as a result of it. The only factor associated with an increased risk of malignancy in our population was smoking history. CONCLUSIONS: Almost 10% of lung transplant recipients developed some type of noncutaneous neoplasia and the most frequently diagnosed were PTLDs. Lung neoplasia compromised most survival in these patients. PMID- 26680066 TI - Autologous Stem Cell Transplantation in Patients With Primary Systemic Amyloidosis: Experience of a Tertiary Hospital. AB - BACKGROUND: Systemic immunoglobulin light-chain (AL) amyloidosis is a plasma cell dyscrasia that results from the deposition of insoluble fragments of immunoglobulin light or heavy chains. The subsequent disruption of organ function resulting from the extracellular deposition of these fragments ultimately leads to death. The median overall survival (OS) of patients ranges from 12 and 18 months down to 5 months in patients with cardiac involvement. Autologous hematopoietic stem cell transplantation (ASCT) is a treatment modality that achieves good response. The affected solid organ transplant (SOT) could improve performance status and have a favorable impact on survival. METHODS: Retrospective analysis of 11 AL amyloidosis patients who received ASCT from 2005 to 2013, 2 of them also underwent SOT. RESULTS: The 5-year OS depending on the number of organs involved (1 vs >=2) was 100% versus 60% (P = .13). With a median follow-up of 4.8 years (range, 1.6-8), 81% of patients are alive maintaining complete hematologic response (n = 6) and very good partial response (n = 3). The 5-year progression-free survival was 80% (range, 42%-94%). Two patients underwent cardiac and renal transplantation as a bridge to ASTC. None of the double transplant patients has died. CONCLUSION: ASCT is an effective treatment option in patients with AL amyloidosis. In those with advanced single organ damage, SOT should be considered to improve the clinical outcome. PMID- 26680067 TI - Mortality of Oncohematological Patients Undergoing Hematopoietic Stem Cell Transplantation Admitted to the Intensive Care Unit. AB - BACKGROUND: Both autologous and allogenic hematopoietic stem cell transplantation (HSCT) are potentially curative treatments for hematological malignancies. Patients with related complications may need admission to the intensive care unit (ICU) for specific therapy and organ support. A consensus on treatment between hematologists and intensive care specialists is essential. METHODS: This observasional, retrospective study included all recipients of HSCT in a third level hospital during 2013 and 2014. Certain parameters were taken into account for patients who needed to be admitted to the ICU, evolution, and ICU and hospital mortality. RESULTS: A total of 228 HSCT were carried out: 127 autologous (55.7%) and 101 allogenic (44.3%). Twenty-four patients were admitted to the ICU; 22 had received allogenic HSCT and 2 autologous. The main underlying conditions were acute leukemias (41.6%) and myelodysplastic syndromes (20.8%). Of these patients, 45.8% were in complete remission and 33.3% were in relapse or progression. Causes of admission to the ICU were mainly respiratory failure (70.8%) followed by shock requiring vasoactive drugs. High values for severity scores were observed for APACHE II 25 (19-28) and SOFA 10 (8-14). During hospitalization, a high percentage of patients had hemodynamic (91.7%), renal (87.5%), hepatic (79.2%), and respiratory (87.5%) failure. Mortality in the ICU was 83.3% and hospitalary, 91.7%. All patients requiring invasive mechanical ventilation died in the ICU. CONCLUSIONS: Of recipient patients of allogenic HSCT, 21.8% were admitted to the ICU, presenting a mortality rate of >95%. The main reason for admission was respiratory failure with requirement of invasive mechanical ventilation. Patients with autologous HSCT presented very few complications needing organ support. PMID- 26680068 TI - Passenger Lymphocyte Syndrome After Simultaneous Pancreas-Kidney Transplantation: A Case Report of an Unusual Cause of Alloimmune Hemolytic Anemia. AB - BACKGROUND: Passenger lymphocyte syndrome (PLS) is a disease in which the donor's lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. CASE REPORT: We report the case of a 39-year-old woman with stage V chronic kidney disease on hemodialysis secondary to poorly controlled diabetes mellitus type 1. She received a simultaneous pancreas-kidney transplant from a cadaver donor. The donor was A- and the recipient was A+ without initial complications with normal renal and pancreatic function, and her hemoglobin (Hb) level was 10.2 g/dL at discharge. Four weeks later she was admitted with acute pyelonephritis of the renal graft, with a Hb level of 7.5 g/dL, creatinine level of 0.7 mg/dL, and glucose level of 80 mg/dL. The study of anemia showed direct polyspecific direct Coombs weakly positive (w/+), presenting 2 alloantibodies against the Rh system: anti-D, anti-E. We increased Prednisone dose to 1 mg/kg/d and then decreased it in a pattern. Eight days after discharge, without transfusion, her Hb level was 9.9 g/dL and then it normalized. CONCLUSIONS: PLS is a very rare condition and should be suspected in the first few weeks after transplantation. In our case anemia was probably due to a residual population of Rh-negative donor cells in the transplanted pancreas kidney received. It is usually a sudden onset of hemolytic anemia in patients with a solid organ transplant and different Rh or ABO lower incompatibility. PMID- 26680069 TI - Likely Recurrence of C3 Glomerulonephritis in Kidney Transplantation: An Entity to Bear in Mind: Case Report. AB - BACKGROUND: C3 glomerulonephritis (C3GN) is an unusual entity that is caused by dysregulation and hyperactivity of the alternative complement pathway. Renal biopsy immunofluorescence study shows C3 deposits with absence of immunoglobulins and markers of the classical complement pathway. More than 50% of cases develop end-stage renal disease. Less well-known is the course of C3GN after kidney transplantation. CASE REPORT: We present the case of a 60-year-old woman with chronic kidney disease secondary to chronic glomerulonephritis of unknown origin who received a kidney transplant. Two years later, she presented worsening renal function with non-nephrotic proteinuria and microhematuria. Complement testing revealed low serum levels of C3. Kidney biopsy showed alterations compatible with C3GN that we interpreted as a relapse of the underlying disease. PMID- 26680070 TI - New Antivirals for Hepatitis C Infection Among Infected Kidney Transplant Recipients: A Case Report. AB - The most common hepatopathy in end-stage renal disease is chronic hepatitis C virus (HCV) infection, which decreases allograft and patient survival in kidney transplants. Until last year we did not have treatments free of interferon, which was contraindicated after renal transplantation owing to the risk of allograft rejection. Recently, new drugs have been discovered for interferon-free regimens. These drugs present a cure rate of up to 90% and can be used in transplant recipients. Here we present our 1st 3 cases. In our experience, new antivirals have proven to be effective and safe for the treatment of HCV hepatopathy in kidney transplant recipients and liver-kidney transplantation, thus helping us to prevent complications related to HCV infection in transplant recipients. PMID- 26680071 TI - Patients After Kidney Allograft Failure: Immunologic and Nonimmunologic Considerations. AB - Patients returning to dialysis after kidney transplant failure represent approximately 5%-15% of the population starting hemodialysis. These patients exhibit a high risk of morbidity and mortality attributed mainly to the exposure to immunosuppressive medications and to a uremic environment. The purpose of this paper was to review data regarding survival after renal allograft failure and the optimal management of patients before returning to dialysis. Moreover, issues surrounding nephrectomy after renal allograft failure, the tapering of immunosuppression and the possibility of retransplantation are examined, because they seem to be crucial for patient survival and the quality of life. PMID- 26680072 TI - Key Points in Establishing a Model of Mouse Liver Transplantation. AB - The explosion of interest in research into the mouse genome and immune system has meant that the mouse orthotopic liver transplantation (MOLT) model has become a popular means of studying transplantation immunity, organ preservation, ischemia reperfusion injury, and surgical techniques, among others. Although numerous modifications and refinements of surgical techniques have simplified the operation, the relatively short duration of postoperative survival after MOLT remains an obstacle to longer-term follow-up studies. Here, we summarize the scientific basis of MOLT and our experience improving and refining the model in six key areas: anesthesia, operative technique, perfusion and preservation of the liver, cuff technique, anhepatic time, and the value of rearterialization for the liver graft. We also compare the characteristics of different surgical techniques, and give recommendations for the best means of tailoring technique to the objectives of a study. In doing so, we aim to assist other investigators in establishing and perfecting the MOLT model in their routine research practice. PMID- 26680073 TI - Hand-assisted Laparoscopic Donor Nephrectomy and Cytokine Changes. AB - BACKGROUND: Laparoscopic living-donor nephrectomy (LDN) exerts systemic effects causing transaminitis and increased urinary neutrophil gelatinase-associated lipocalm (NGAL) excretion. Hand-assisted laparoscopic donor nephrectomy, which tends to be shorter with less pneumoperitoneum, may be hypothesized to produce less systemic stimulation than total laparoscopic LDN. METHODS: Serial urine and serum samples were collected from 15 patients undergoing HALDN. Samples were analyzed for NGAL and kidney injury molecule 1 (KIM-1) levels preoperatively and 24 hours post-surgery. Data relating to alanine aminotransferase, creatinine, and estimated glomerular filtration rate was also analyzed in 48 live donors preoperatively and at 24 hours and 48 hours post-surgery and compared to published data on LDN. RESULTS: Expected changes to creatinine and estimated glomerular filtration rates were observed in the donors. Compared to the preoperative levels, alanine aminotransferase levels showed a significant decrease at 24 hours (P = .004) and were not significantly different from baseline levels at 48 hours (P = .08). Serum KIM-1 and NGAL levels remained unchanged (P = .89 and P = .14, respectively) at 24 hours after donation. Similarly, urinary levels of KIM-1 and NGAL were not statistically significantly different after donation. Mean operating time for this cohort was 1 hour, 36 minutes. CONCLUSIONS: In contrast to other published data, our cohort did not exhibit changes to liver function tests or biomarker changes after donor nephrectomy. This could be because of the lower operative time (96 minutes vs. 216 minutes) or because of the intermittent release of the pneumoperitoneum in the hand-assisted method which may exert less of a systemic inflammatory response. PMID- 26680074 TI - Outcomes and Mortality in Renal Transplant Recipients Admitted to the Intensive Care Unit. AB - INTRODUCTION: In the intensive care unit (ICU), mortality is considered higher among renal transplant recipients than among nontransplantation patients. However, data regarding severe complications after kidney transplantation are scarce. MATERIALS AND METHODS: In this study, we evaluated all consecutive renal transplant recipients admitted to our ICU between July 2012 and July 2013 (n = 70), comparing their outcomes with those of a control group of nontransplantation patients admitted during the same period (n = 153). Among the transplant recipients, we compared survivors and nonsurvivors to identify predictors of ICU mortality. RESULTS: The mean age of the transplant recipients was 52 +/- 13 years. Of the 70 transplant recipients, 18 (25%) required mechanical ventilation, 28 (40%) required inotropic support, and 27 (39%) required hemodialysis, all of which are factors that worsen the prognosis significantly. Twenty-two (31%) of the transplant recipients died in the ICU and 17 (24%) died within 30 days after ICU discharge, rates similar to those observed for the control group. CONCLUSIONS: We observed similar mortality between recipient and control groups, albeit the mortality was higher in the clinical group. In the multivariate model, the need for mechanical ventilation and the need for hemodialysis were independently associated with mortality. PMID- 26680075 TI - Comparison of Renal Scintigraphy and Computed Tomographic Renal Volumetry for Determining Split Renal Function and Estimating Post-Transplant Renal Function. AB - BACKGROUND: In living donor kidney transplantation, the decision regarding which donor kidney to transplant is based on characteristics such as vascular anatomy and split renal function (SRF). Computed tomography (CT) was used to assess vascular anatomy and renal scintigraphy was used to evaluate SRF. The ability of split renal volume (SRV) calculated from volumetric examination of CT scans and that of SRF of renal scintigrams derived from Tc-99m mercaptoacetyltriglycine-3 (MAG3) renography to predict donor residual single kidney function after donor nephrectomy were compared. MATERIAL AND METHODS: CT images and renal scintigrams from 35 live kidney donors who had at least 1 year post-donation renal function follow-up were analyzed. RESULTS: Predonation GFR was 99.1 +/- 17.2 mL/min/1.73 m(2). The average right and left kidney volumes were 138.8 +/- 29.4 mL and 136.1 +/- 29.2 mL, respectively. SRV was strongly and significantly correlated with SRF MAG3 (r = 0.714). The residual renal functions predicted from calculating SRV and SRF-MAG3 were 46.2 +/- 8.3 mL/min/1.73 m(2) and 46.0 +/- 9.2 mL/min/1.73 m(2), respectively. Both SRV (r = 0.708) and SRF-MAG3 (r = 0.634) showed significant linear correlations with residual renal function after 1 year, with SRV showing a stronger correlation. CONCLUSION: Calculating SRV from predonation CT examination is a valid method to estimate postdonation renal function after 1 year. CT volumetry may become a standard method in the near future. PMID- 26680076 TI - Serum Fetuin A Levels: Are They a Reliable Marker for Hepatic Steatosis and Regional Adiposity in Renal Transplant Recipients? AB - BACKGROUND: Fetuin A is a protein expressed in the liver and it is an important inhibitor of ectopic calcification. High levels of fetuin A correlate with insulin resistance, hepatic steatosis, and regional adiposity in the general population. The association between hepatic steatosis and fetuin A level in renal transplant recipients (RTRs) remains unclear. AIM: The aim of this study was to explore the relationships between fetuin A, hepatic steatosis, and regional adiposity in RTRs. METHODS: Data from 44 patients with normal renal functions were included, all subjected to history taking for clinical data, assessment of central obesity and regional adiposity, assessment of hepatic steatosis using abdominal ultrasound (US), and measurements of serum fetuin A concentration using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Our study included 20 females (45.4%) and 24 males (54.6%) with mean age of 41.26 +/- 11.2 years. Twenty-four subjects had hepatic steatosis. Fetuin A level in RTRs with hepatic steatosis with a mean of 1642.92 +/- 358.91 is significantly higher (P < .001) than those without hepatic steatosis with a mean of 711.74 +/- 57.85. Serum fetuin A level was positively correlated with regional adiposity (P = .021) and hepatic steatosis grade (P = .017). Fetuin A level increased with increased duration after renal transplantation (P < .001). The best cutoff value for detecting entrance into phase 3 or 4 steatosis is fetuin of 1862 with sensitivity of 88.9% and specificity of 87.7%. CONCLUSIONS: Fetuin A is positively correlated with hepatic steatosis and regional adiposity in RTRs. Fetuin increases with increased duration after renal transplantation. Accordingly it may be used as a marker for hepatic steatosis and regional adiposity in these patients. PMID- 26680077 TI - Low Adherence to Immunosuppressants Is Associated With Symptom Experience Among Kidney Transplant Recipients. AB - PURPOSE: The purpose of this study was to investigate the relationship between immunosuppressant-related symptom experience (SE) and adherence to immunosuppressant regimens among kidney transplant (KT) recipients. METHODS: A total of 239 KT recipients on an immunosuppressant regimen who were followed up after transplantation participated in this study. Data was collected through a self-reported questionnaire survey (medication adherence, SE, and quality of life) and medical record review. RESULTS: Low adherence in the immunosuppressant group was associated with longer time since KT, less comorbidity (<3), and a higher rehospitalization rate. Low adherence among KT recipients showed significantly greater overall symptom occurrence (P = .001) and symptom distress (P = .002) levels than patients with high or medium adherence after adjusting for a number of covariates. The most common symptom both in terms of occurrence (96.4%) and distress (91.1%) among poorly adherent KT recipients was tiredness. CONCLUSION: Low adherence to an immunosuppressant regimen was significantly associated with high SE among KT recipients. Strategies to decrease immunosuppressant-related SE are needed to improve adherence to immunosuppressants. PMID- 26680078 TI - Effects of Continuous Octreotide Infusion on Intraoperative Transfusion Requirements During Orthotopic Liver Transplantation. AB - Orthotopic liver transplantation (OLT) is often associated with major hemorrhage and a large red blood cell (RBC) transfusion requirement. Massive transfusion during OLT has been associated with decreased patient and graft survival. As a result, the anesthesiologist may use various techniques to decrease intraoperative blood loss and transfusion requirements, including maintenance of a low central venous pressure, antifibrinolytic drugs, cell salvage, and vasopressors. Due to its properties of splanchnic vasoconstriction and resultant decrease in portal venous blood flow, octreotide may decrease blood loss during the preanhepatic phase of OLT. We performed a retrospective review of 50 consecutive liver transplantations; a continuous octreotide infusion was used during the preanhepatic phase in 30 of these cases. We hypothesized that intraoperative transfusion requirements would be reduced in those patients treated with octreotide. Statistical analysis found that the number of RBCs transfused decreased from 20.4 U to 18.1 U when octreotide was used, although this result was not statistically significant (P = .5). Additional analysis found a significant positive correlation between the number of RBCs transfused and total operating room (OR) time, preoperative international normalized ratio (INR), and model for end-stage liver disease (MELD) and a negative correlation between the number of RBCs transfused and preoperative platelets and hemoglobin. Although our small study did not show a statistical difference in the number of units transfused, there was an absolute difference. A prospective, randomized trial would be useful in elucidating the true effect of octreotide on RBC transfusion requirements during OLT. PMID- 26680079 TI - Measles Virus Infection in Pediatric Liver Transplantation Recipients. AB - OBJECTIVE: This study was conducted to analyze the clinical characteristics and outcome of measles in pediatric liver transplant recipients. METHODS: This study includes a retrospective data analysis of five pediatric liver transplant recipients with measles who were treated at the Liver Transplant Section, Beijing Friendship Hospital, China, from March to April 2014. RESULTS: The clinical manifestations of measles in pediatric liver transplant recipients were serious. There were three cases complicated with pneumonia, and one with laryngitis. Two cases presented with severe measles pneumonia that developed into severe respiratory failure requiring mechanical ventilation. Four patients recovered after treatment and one patient died of respiratory failure. CONCLUSION: Pediatric liver transplant recipients with measles are at high risk of severe pneumonia. Measles pneumonitis is frequently fatal to immunocompromised pediatric patients. Treatment should be initiated as soon as possible. PMID- 26680080 TI - Hypothermic Circulatory Arrest in Cardiac Transplantation. AB - PURPOSE: Infrequently, hypothermic circulatory arrest (HCA) must be used during cardiac transplantation. Such cases may include concomitant aortic arch surgery, explantation of ventricular assist devices with outflow grafts or pseudoaneurysms closely abutting the sternum, and other scenarios for which dense mediastinal adhesions preclude exposure and anatomic dissection by conventional methods of adhesiolysis. Outcomes of heart transplantations performed with HCA have not been previously catalogued in the literature and are presented in the current case series. METHODS: Between November 2012 and December 2014, 193 patients underwent heart transplantation at a single institution. Of these, 7 cases (3.6%) required implementation of HCA. Postoperative outcomes in these patients were analyzed using a prospectively maintained clinical database. RESULTS: The HCA patients included 28% females, with mean age of 46 years, and 71% had nonischemic cardiomyopathies. The majority (N = 5, 71%) had prior ventricular assist device implantation, including 1 patient with a paracorporeal biventricular assist device. One of the remaining 2 patients had three previous surgeries for repair of tetralogy of Fallot, with a completely calcified right ventricular outflow tract and pulmonary arterial system. Mean HCA and cold ischemic times were 25 minutes (range, 9-34 minutes) and 285 minutes (range, 181-425 minutes), respectively. Mean postoperative length of stay was 31 days, and six of seven patients (86%) survived to hospital discharge. One patient expired as an outpatient 2 months following transplant. Rates of postoperative renal failure, respiratory failure, and stroke were 43%, 43%, and 29%, respectively. CONCLUSION: On rare occasions, HCA must be instituted to safely conduct a complex heart transplantation procedure. Based on this small case series, these patients can be salvaged and discharged from the hospital, but may experience prolonged lengths of stay with moderate rates of other end-organ complications. PMID- 26680081 TI - Combined Heart and Liver Transplantation: The Cedars-Sinai Experience. AB - PURPOSE: Combined heart-liver transplantation is an increasingly accepted treatment for select patients with heart and liver disease. Despite growing optimism, heart-liver transplantation remains an infrequent operation. We report our institutional experience with heart-liver transplantation. METHODS: All combined heart-liver transplantations at Cedars-Sinai Medical Center from 1998 2014 were analyzed. Primary outcomes were patient and graft survival and secondary outcomes included rejection, infection, reoperation, length of stay, and readmission. RESULTS: There were 7 heart-liver transplants: 6 simultaneous (single donor) and 1 staged (2 donors). Median follow-up was 22.1 (IQR 13.2-48.4) months. Mean recipient age was 50.8 +/- 19.5 years. Heart failure etiologies included familial amyloidosis, congenital heart disease, hypertrophic cardiomyopathy, systemic lupus erythematosus, and dilated cardiomyopathy. Preoperative left ventricular ejection fraction averaged 32.3 +/- 12.9%. Five (71.4%) patients required preoperative inotropic support; 1 required mechanical circulatory support. The most common indications for liver transplant were amyloidosis and cardiac cirrhosis. Median Model for End-stage Liver Disease score was 10.0 (9.3-13.8). Six-month and 1-year actuarial survivals were 100% and 83.3%, with mean survival exceeding 4 years. No patient experienced cardiac allograft rejection, 1 experienced transient liver allograft rejection, and 1 developed progressive liver dysfunction resulting in death. Five developed postoperative infections and 3 (42.9%) required reoperation. Median ICU and hospital stays were 7.0 (7.0-11.5) and 17.0 (13.8-40.5) days. There were 4 (57.1%) readmissions. CONCLUSIONS: For carefully selected patients with coexisting heart and liver disease, combined heart and liver transplantation offers acceptable patient and graft survival. PMID- 26680082 TI - Relationship Between Hyperglycemia and Heart Transplant Rejection. AB - PURPOSE: Hyperglycemia increases risks of kidney and liver transplant rejection. To determine whether perioperative and subsequent glycemic control was associated with increased risk of heart transplant rejection over the year after transplantation, we performed a retrospective analysis of glycemic control and rejection rates in heart transplantation patients. METHODS: Perioperative glucose levels were analyzed in 157 patients undergoing transplantation at Northwestern Memorial Hospital from June 2005 to December 2012 and compared in patients with and without rejection found on routine follow-up biopsy specimens. RESULTS: Grade <=1R rejection on biopsy was observed in 116 patients and grade >=2R rejection (grade requiring increased anti-rejection treatment) in 41 patients. Although no significant differences in the preoperative fasting or inpatient mean glucose levels were found, the mean glucose levels from discharge to 1 year trended higher in those with grade >=2R compared to grade <=1R (128.8 +/- 40.9 versus 142.2 +/- 46.6 mg/dL, P = .084). In a multivariable logistic regression model, neither the lowest nor highest quartile of glucose levels had significantly different odds ratios (ORs) for the development of >=2R compared to the middle 50% glucose levels. Older age (OR 0.96, P = .020) and higher body mass index levels (OR 0.86, P = .004) were significantly associated with lower odds of developing grade >=2R. CONCLUSIONS: Although the glucose trend regarding rejection was not statistically significant, we cannot exclude the possibility that much higher glucose levels would influence rejection rates. PMID- 26680083 TI - Left Ventricular Dysfunction After Lung Transplantation for Pulmonary Arterial Hypertension. AB - BACKGROUND: Lung transplantation (LT) is the final treatment option for patients with pulmonary arterial hypertension (PAH). Perioperative challenges after LT are unique and commonly include excessive bleeding, arrhythmias, and primary graft dysfunction. Transient left ventricular dysfunction (LVD) is a known postoperative complication, but not fully explored. We describe our experiences at a single institution. METHODS: We reviewed our database for patients with PAH who underwent LT from July 2008 to July 2012. The data were analyzed for preoperative inotrope use, intravenous prostacyclin, cardiac catheterization, and imaging. Also measured were perioperative ischemic time, bypass time, primary graft dysfunction, ventilator days, length of stay, and mortality. LVD is defined as acute cardiopulmonary compromise (acute worsening of hypoxia with new bilateral infiltrates on imaging) with a drop in LV systolic function of 15% from baseline. We compared data between patients with LVD and without LVD. RESULTS: Sixteen patients met the criteria, the majority of patients (10) with World Health Organization (WHO) group 1 PAH. Thirteen received intravenous prostacyclin therapy, and 6 required inotropes before surgery. Five patients (31%) developed LVD after transplantation. Average time to onset of LVD was 4.2 days. Preoperative vasopressors were required in 60% of those developing LVD. Patients with LVD had lower right and left ventricular ejection fraction with higher left ventricular end diastolic volume before surgery. All patients recovered from LVD within 4 months after LT. CONCLUSIONS: LVD is a phenomenon observed mostly in patients with WHO group 1 PAH receiving LT. Prompt recognition and treatment of this condition reduced morbidity. PMID- 26680084 TI - Use of Extracorporeal Membrane Oxygenation Prior to Lung Transplantation Does Not Jeopardize Short-term Survival. AB - BACKGROUND: The use of pretransplantation extracorporeal membrane oxygenation (ECMO) has been considered to be a relative contraindication and a risk factor associated with poor outcomes in lung transplantation. However, with a donor shortage, use of ECMO before transplantation is often unavoidable. This study aimed to review our experiences of lung transplantation outcome with regards to the use of pretransplantation ECMO. METHODS: We retrospectively reviewed the clinical data of patients who underwent lung transplantation at our institution. Clinical variables as well as ECMO-related data were analyzed with surgical outcomes. RESULTS: From 2006 to 2014, 27 patients underwent lung transplantation: 26 bilateral sequential lung transplants and 1 right-side single lung transplant. Of these, 12 (44.4%) received ECMO treatment during the pretransplantation waiting period. Pretransplantation ECMO patients showed higher body mass index scores (P = .047) and mechanical ventilation support (P < .001) than the non-ECMO group. All ECMO patients were weaned from ECMO after transplantation. The median ECMO runtime was 12 days. The survival-to-discharge rates of the 2 groups did not differ. Survival after lung transplantation at 1, 6, 12, and 24 months was 100%, 73.3%, 61.1%, and 61.1% in the ECMO group and 100%, 86.7%, 86.7%, and 66.0% in the non-ECMO group, respectively (P = .540). CONCLUSIONS: Use of pretransplantation ECMO did not jeopardize survival-to-discharge and short-term survival rates in our experience. Our result suggests pretransplantation ECMO can provide a chance of receiving lung transplantation to those who were classified as "too sick to be transplanted." PMID- 26680085 TI - Relative Safety of External Beam Radiation Therapy in Lung Transplant Recipients Who Develop Thoracic Malignancies. AB - We report outcomes for three patients who previously received lung transplants, subsequently developed malignancies, and were given radiation therapy to the chest for treatment of their cancers despite lack of scientific data on radiation tolerance of transplanted lung. None of three patients exhibited early or delayed adverse reactions to radiotherapy. For these three cases, the mean dose to the ipsilateral transplanted lung was 10 Gy, and ipsilateral lung relative volume of lung receiving 20 Gy or more was, on average, 22%. These doses are relatively low and would have been considered safe for patients with native lungs. In our opinion, tolerance of transplanted lung to therapeutic radiotherapy clearly requires additional research. While those data are pending, radiation therapy to the thorax should not be ruled out on the basis of having a lung transplant alone, provided lung dose can be maintained as low as possible using meticulous treatment planning. PMID- 26680086 TI - Protective Effect of Antiapoptosis Potency of Prolonged Preservation by Desiccation Using High-Pressure Carbon Monoxide on Isolated Rabbit Hearts. AB - Heart transplantation has been widely accepted as a therapy for end-stage heart failure. Mitigation of ischemia-reperfusion injury by inhibiting the apoptotic process plays an important role in organ transplantation. Desiccation using high pressure carbon monoxide (CO) is a new method of preserving donor hearts; however, its mechanism of antiapoptosis remains unclear. This study was intended to elucidate the efficacy and mechanism of preservation by desiccation for 18 hours using high-pressure CO on myocardial apoptosis. Rabbit heterotopic abdominal cardiac transplantation models were established. New Zealand rabbits were divided randomly into 3 groups: naive group (n = 16), HTK group (n = 16), and desiccation using high-pressure CO group (n = 16). The donor hearts of the naive group were transplanted immediately after being extracted. In the HTK group, the donor hearts were extracted and steeped in 4 degrees C HTK cardioplegic solution for 18 hours and then transplanted; in the desiccation using high-pressure CO group, the donor hearts were extracted and exposed to a gas mixture (Po2 = 3200 hPa, Pco = 800 hPa) in the chamber before being preserved in a refrigerator at 4 degrees C for 18 hours and then transplanted. Apoptotic cardiomyocytes were detected using TUNEL technique and histopathology was performed by hematoxylin-eosin staining. The expression of the ratio of Bcl-2/Bax and caspase-3 proteins was detected using the Western blot method. These findings suggest that compared with traditional HTK preservation, preservation by desiccation using high-pressure CO could alleviate rabbits' myocardial histopathology and apoptosis induced by ischemia-reperfusion injury through adjusting the ratio of Bcl-2/Bax protein expression, thus resulting in the reduction of expression of caspase-3. PMID- 26680087 TI - Effect and Mechanism of Portal Blood Stasis Removal on Intestinal Endotoxemia and Hepatic Ischemia Reperfusion Injury. AB - OBJECTIVE: We used a rabbit model of hepatic ischemia reperfusion in situ to observe the change of portal venous endotoxin level before reperfusion, and the effect of portal blood stasis removal on intestinal endotoxemia and hepatic ischemia reperfusion injury. The purpose was to find an ideal method for portal blood stasis removal and provide the experimental proof for clinical application of hepatectomy. METHODS AND MATERIALS: To investigate the effect of portal blood stasis removal on intestinal endotoxemia and hepatic ischemia reperfusion injury, a rabbit hepatic ischemia reperfusion injury model was established and treated with removal of portal blood stasis before the portal blood circulation was resumed. Serum endotoxin content, alanine aminotransferase (ALT), hyaluronic acid (HA), and content of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6), superoxide dismutase (SOD) and activation of nuclear factor-kappaB (NF-kappaB) in liver tissue were examined respectively. RESULTS: In portal blood stasis the level of serum endotoxin significantly decreased with each 2.5 mL blood removal (P < .01), subsequently reaching a minima at the 7.5 mL blood removal (P > .05). Removing portal blood stasis ameliorated endotoxemia and hepatic ischemia reperfusion injury as shown by ALT, HA, MDA, SOD, TNF-alpha, IL-6, and activation of NF-kappaB compared to no removal. The first 5 mL portal blood stasis contains high volume of endotoxin which may be responsible for hepatic reperfusion injury. CONCLUSION: Removal of portal blood stasis before the resume of splanchnic circulation may ameliorate intestinal endotoxemia and hepatic ischemia reperfusion injury. PMID- 26680088 TI - N-Acetylcysteine and High-Dose Atorvastatin Reduce Oxidative Stress in an Ischemia-Reperfusion Model in the Rat Kidney. AB - OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties. PMID- 26680089 TI - Formation of Cholangiogenic Cysts Following Intrahepatic Islet Transplantation in Streptozotocin Diabetic Rats. AB - Permanent hyperinsulinemia and the resulting overstimulation of the insulin receptor signaling pathway is suspected as a trigger of cancer genesis in the livers of type 2 diabetic patients. Liver tissue (LT) surrounding transplanted pancreatic islets (PI) can be permanently exposed to insulin in even higher concentrations than in type 2 diabetic patients. Therefore, this study examines the effect of PI transplantation (Tx) on LT in animals with streptozotocin (STZ) induced diabetes mellitus. The suboptimal mass (400 or 1000) of isogeneic PI was transplanted into either the portal vein or under the kidney capsule of diabetic Brown Norway (BN) rats. Healthy BN rats treated with 400 isogeneic PI transplanted in the portal vein served as a control group. During the first 6 months after PI Tx, small and infrequent cystic lesions developed in animals with STZ diabetes, irrespective of the Tx site. In 10 months, frequent and complex cystic lesions appeared in these animals. In the control group, several small lesions were detected but not until 10 months after the PI Tx. In summary, STZ is the likely main inductor of hepatic cystic lesions, but the contribution of PI was not confirmed. PMID- 26680090 TI - Case Report of Relay Liver Transplantation With Graft Infected With Hepatitis B Virus. AB - Reuse of liver graft for transplantation is extremely uncommon. We report the 1st case of reuse of liver graft from a recipient who had hepatitis B virus (HBV) infection, 11 years after the 1st transplantation. Our relay liver transplantation challenged conventional thinking because of late reuse of graft in the presence of HBV infection. Moreover, both the 1st and the 2nd donors were of advanced age. The key questions were whether the liver graft could be reused safely, especially in the setting of HBV infection, and technical concerns during organ procurement and implantation. The absence of HBV replication was confirmed with negative hepatitis B surface antigen and undetectable serum HBV DNA in the 2nd donor. Based on our experience in managing HBV infection after liver transplantation, we were confident that the adequately suppressed HBV infection in the donor would not jeopardize graft function and that the graft would be able to withstand another ischemia-perfusion injury to continue to function well in our recipient. PMID- 26680091 TI - Successful Treatment of Mitochondrial Toxicity in an HIV-Positive Patient After Liver Transplantation. AB - Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient. PMID- 26680092 TI - Asymptomatic De Novo Inflammatory Bowel Disease Late After Liver Transplantation for Primary Sclerosing Cholangitis: A Case Report. AB - Guidelines recommend colonoscopy screening for possible asymptomatic inflammatory bowel disease (IBD) in all patients diagnosed with primary sclerosing cholangitis (PSC). PSC-IBD warrants regular dysplasia-surveillance colonoscopy. However, no consensus exists regarding follow-up colonoscopy in PSC patients without IBD who remain asymptomatic. We describe a 43-year-old female who had undergone liver transplantation (LT) due to advanced PSC. Previous colonoscopies had been normal. The post-transplantation course was uneventful, with no rejections and signs of PSC recurrence. Immunosuppression was by tacrolimus monotherapy. She was asymptomatic with normal inflammation markers. A protocol colonoscopy, performed as general dysplasia surveillance 8 years post-transplantation, revealed mucopurulent-covered small superficial ulcerations and erythema diffusely distributed from the cecal to sigmoid colon with intervening normal mucosa and rectal sparing. Histologic examination showed patchy chronic colitis with crypt architectural distortion and mild-moderate inflammation activity. Infection samples were negative. Findings complied with de novo IBD, type unclassified. In conclusion, the link between PSC and clinically silent IBD may manifest after the PSC diagnosis and even several years after LT. Given the increased colorectal cancer risk associated with PSC, IBD, and LT, repeat colonoscopy might be warranted in PSC patients without IBD at initial assessment, and also after LT. PMID- 26680093 TI - Successful Living-Donor Liver Transplantation for Cholestatic Liver Failure Induced by Allopurinol: Case Report. AB - A 39-year-old man was diagnosed with allopurinol-induced hepatic injury. He did not show any sign of hepatic encephalopathy, but his serum total bilirubin level was >40 mg/dL when he visited the local hospital. The therapeutic effects of initial medical treatments were transient, and both renal function and coagulation ability were gradually deteriorated. Four months after the onset of hepatic injury, he was referred to our hospital for the purpose of liver transplantation (LT). Although he was wasting and severely jaundiced, his consciousness level was not disturbed at all, with normal serum ammonia blood concentration before LT. Owing to allopurinol-induced severe cholestatic liver failure, living-donor LT (LDLT) was performed with the use of a right lobe graft from his younger brother. The explanted liver was extremely enlarged, with a weight of 2,480 g, and severely cholestatic. Microscopic findings were also compatible with drug-induced cholestatic liver injury. He was discharged from hospital 55 days after LDLT, whereas his renal dysfunction remained at 6 months after LT. There are 3 types of pathophysiology of drug-induced hepatotoxicity: hepatocellular, cholestatic, and mixed liver injury. Although allopurinol hepatotoxicity is rare, it can be severe and even fatal. This is the 1st case report of successful LDLT for a patient who had developed allopurinol-induced cholestatic liver failure. PMID- 26680094 TI - Is There a Role for Desmopressin in Liver Transplantation? A Case Report. AB - Living donor liver transplantation reduces time and mortality on the waiting list. Bleeding is a serious complication; however, "overcorrection" of coagulopathy may lead to hepatic artery thrombosis. We report a case where desmopressin (DDAVP) was used in the management of persistent postreperfusion bleeding (44 red blood cell units transfused). After 1 dose of DDAVP, bleeding improved significantly and the recipient had an unremarkable recovery. DDAVP should be considered for persisting bleeding after correcting common coagulation abnormalities where complexity of the anastomosis may preclude the use of more aggressive procoagulant drugs in liver transplantation. PMID- 26680095 TI - Cryptococcosis Presenting as a Colonic Ulcer in a Kidney Transplant Recipient: A Case Report. AB - We present a case of a 59-year-old woman with Chagas disease who received a kidney transplant. At month 44 post-transplantation, the patient presented with diarrhea that had persisted for 2 months. Colonoscopy showed a colon ulcer and differential diagnoses included cytomegalovirus, bacteria, or parasite infection; drug-related diarrhea; Crohn's disease; celiac disease; and malignancy. The ulcer tissue was positive for Cryptococcus neoformans. Successful treatment consisted of amphotericin B for 8 days and oral fluconazole (800 mg daily) for 3 months. This case illustrates that a colonic ulcer, although rare, could be cryptococcosis. PMID- 26680096 TI - Retrobulbar Hematoma After Heart Transplantation: Case Report and Literature Review. AB - Spontaneous retrobulbar hemorrhage is a rare phenomenon observed after surgery not directly involving the orbit. When it occurs, presentation is usually obvious, and it carries high morbidity unless emergent and timely surgical treatment is instituted. There are only a handful of cases associated with cardiac surgery, and to our knowledge no cases with heart transplantation. We present a case of a 35-year-old woman who underwent orthotopic heart transplantation for peripartum cardiomyopathy and developed spontaneous retrobulbar hemorrhage. PMID- 26680097 TI - Renal Transplantation in HIV-positive Renal Transplant Recipients: Experience at the Mannheim University Hospital. AB - Renal transplantation in HIV-positive patients with end-stage renal disease has in recent years become a successful treatment option. We report two patients who underwent renal transplantation using a combination of basiliximab, calcineurin inhibitors, mycophenolate mofetil (MMF), and steroids with a "non-interacting" antiretroviral combination therapy consisting of stavudine or abacavir, lamivudine, and nevirapine. We observed no acute rejection but a BK polyomavirus infection in both patients. In conclusion, a quadruple immunosuppression with an interleukin 2 receptor antagonist, a calcineurin inhibitor, MMF, and steroids appears to be advisable to prevent high rates of acute rejection, but if possible thereafter immunosuppression should be tapered rapidly (eg, MMF stop, prednisolone dose 5 mg/d). The selection of antiretroviral agents should avoid compounds that interact severely with the immunosuppression used. PMID- 26680098 TI - Pros and cons of pDNA and mRNA transfection to study mRNA translation in mammalian cells. AB - Protein synthesis in eukaryotes is subject to stringent control. The misregulation of translation of certain mRNAs is often a hallmark of many diseases, including malignancies and autoimmune disorders. To understand why and how it happens, it is important to investigate the translational control of specific mRNAs. In this case, one could use reporter mRNAs in order to identify cis-acting elements responsible for regulation. Here we overview plasmid DNA (pDNA) and mRNA transfections, their pitfalls and limitations, as well as some emerging applications for mRNA transfection. PMID- 26680099 TI - Overexpression of the BRIP1 ameliorates chemosensitivity to cisplatin by inhibiting Rac1 GTPase activity in cervical carcinoma HeLa cells. AB - BRCA1-interacting protein 1 (BRIP1), a DNA-dependent ATPase and a DNA helicase, is critical for BRCA-associated DNA damage repair functions and may be associated with the tumourigenesis and aggressiveness of various cancers. Here, we constructed a BRIP1 recombinant plasmid, overexpressed it in a cervical cancer cell line (HeLa) and found that ectopic expression of BRIP1 could remarkably enhance the antitumor activity of cisplatin, as demonstrated by decreased cell viability, colony formation and tumour xenografts' weight. Moreover, BRIP1 promoted cisplatin-mediated cell apoptosis and suppressed tumour angiogenesis. We also found that the synergistic inhibition effect of BRIP1 might be partially attributed to attenuation of Rac1 GTPase activation and that Rac1 GTPase re activation could reverse the sensitizing effect induced by BRIP1. Our study suggested that up-regulation of BRIP1 could enhance chemosensitivity of HeLa cells to cisplatin through inhibiting Rac1 GTPase activation, and it provides a new insight into the essential role of BRIP1 in cervical cancer chemotherapy. PMID- 26680100 TI - The complete chloroplast genome of Gentiana straminea (Gentianaceae), an endemic species to the Sino-Himalayan subregion. AB - Endemic to the Sino-Himalayan subregion, the medicinal alpine plant Gentiana straminea is a threatened species. The genetic and molecular data about it is deficient. Here we report the complete chloroplast (cp) genome sequence of G. straminea, as the first sequenced member of the family Gentianaceae. The cp genome is 148,991bp in length, including a large single copy (LSC) region of 81,240bp, a small single copy (SSC) region of 17,085bp and a pair of inverted repeats (IRs) of 25,333bp. It contains 112 unique genes, including 78 protein coding genes, 30 tRNAs and 4 rRNAs. The rps16 gene lacks exon2 between trnK-UUU and trnQ-UUG, which is the first rps16 pseudogene found in the nonparasitic plants of Asterids clade. Sequence analysis revealed the presence of 13 forward repeats, 13 palindrome repeats and 39 simple sequence repeats (SSRs). An entire cp genome comparison study of G. straminea and four other species in Gentianales was carried out. Phylogenetic analyses using maximum likelihood (ML) and maximum parsimony (MP) were performed based on 69 protein-coding genes from 36 species of Asterids. The results strongly supported the position of Gentianaceae as one member of the order Gentianales. The complete chloroplast genome sequence will provide intragenic information for its conservation and contribute to research on the genetic and phylogenetic analyses of Gentianales and Asterids. PMID- 26680101 TI - Genotypic distribution of common variants of endosomal toll like receptors in healthy Spanish women. A comparative study with other populations. AB - Genetic variants of endosomal toll like receptors (TLR) have been associated with many infectious, autoimmune and inflammatory diseases, but few studies have been reported in the Spanish population. The aim of this study was to describe the allelic and genotypic distributions of some common nucleotide substitutions of endosomal TLRs in healthy Spanish women and to compare them with those already published in other population groups. Nine substitutions were analysed in 150 DNA samples from 150 Spanish, non-related healthy females: TLR3 rs3775291 and rs5743305; TLR7 rs179008 and rs5743781; TLR8 rs3764880 and TLR9 rs187084, rs5743836, rs352139 and rs352140. Genotyping was carried out by real time PCR and melting curve analysis in a LightCycler 480. A systematic review was performed in order to compare the genotypic distributions in our cohort with those previously published in other population groups. The comparative study was performed with the two tailed Fisher's test or the Yates continuity correction for the Chi square test when appropriate. No homozygotes for rs5743781 in TLR7 were found, and rs352139 and rs352140 of TLR9 were in strong linkage disequilibrium. Genotype distributions in endosomal TLR are similar to other Spanish series previously reported. As expected, most differences were found when comparing our distributions with Asiatics, but differences were also found with other Caucasian populations. Since there are significant variations in genotypic distributions of TLRs in both interracial groups and within the same ethnic group, to carry out studies of disease susceptibility in more restricted groups is mandatory. PMID- 26680102 TI - USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1. AB - Ubiquitin-specific protease 12 (USP12) plays a significant role in tumor cell apoptosis and cell cycle progression. However, the regulatory mechanism of USP12 in human cervical carcinoma HeLa cell growth is unknown. In this study, we showed that knockdown of USP12 effectively induced cell cycle arrest in HeLa cells and decreased BMI-1, c-Myc and cyclin D2 transcription levels. By contrast, unlike the inactive C48S mutant, over-expression of USP12 and the deubiquitinase activity enhanced L153S and R237C mutants, had the opposite effects. Interestingly, compared to wild-type, the L153S mutant resulted in a more effective cell cycle-promotion and increased BMI-1, c-Myc and cyclin D2 transcript levels. In addition to BMI-1, USP12 R237C exhibited a functional resemblance to the wild-type by involving c-Myc and cyclin D2. The effect of USP12 on HeLa cell apoptosis was not observed in our study. These results suggest that USP12 may be responsible for HeLa cell growth by affecting cell cycle progression. PMID- 26680103 TI - A 6-bp deletion in exon 8 and two mutations in introns of TYRP1 are associated with blond coat color in Liangshan pigs. AB - Melanocortin receptor 1 (MC1R), Agouti signaling protein (ASIP), and Tyrosinase related protein 1 (TYRP1) are reported critical genes that regulate pheomelanin and eumelanin synthesis in mammals. Liangshan pig is a special Chinese indigenous pig breed with two completely different coat colors, solid black and blond. In this study, we detected polymorphisms of the above three genes and assessed the relationships between the variations and coat color phenotypes in Liangshan pigs. The findings revealed that the blond phenotype of Liangshan pig was related to dominant mutations in TYRP1, but not related to mutations in MC1R or ASIP. We found three closely linked mutations in TYRP1, g.8406G>A in intron 4, g.11100A>G in intron 5, and g.17599_17604del in exon 8, that were completely associated with blond coat color in Liangshan pigs. Further analysis revealed that a 6-bp deletion mutation resulted in deletion of Met and Gly residues at positions 495 and 496 in TYRP1 protein, and altered the structure of transmembrane domain of TYRP1. Together, our findings indicated that these three mutations in TYRP1 cause the blond phenotype in Liangshan pigs. PMID- 26680104 TI - Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. AB - Quercetin (Que), a plant-derived flavonoid, possesses various biological functions. Moreover, Que exerts multiple beneficial actions in treatment of cardiovascular diseases and there are an inverse association between Que intakes and occurrence and development of various cardiovascular diseases. Some researchers have inferred that the mechanisms of Que to protect cardiomyocytes from ischemia/reperfusion (I/R) injury may be involved in modulation of intracellular signal pathways and regulation of proteins expression in vivo. The current study investigated whether Que has any protective effects on cardiomyocytes from hypoxia/reoxygenation (H/R) in vitro and its potential cardioprotective mechanisms. The cell viability of Que on H9c2 cardiomyoblast cells was assessed by MTT. Apoptosis was evaluated by both Hoechst33342 staining and Flow cytometric analysis (FACS). Furthermore, the effect of Que, SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor) on mitogen-activated protein kinases (MAPKs) and the expression of apoptosis related proteins (Bcl-2, Bax and caspase 3) was determined by Western blotting. MTT assays showed that pretreatment with Que could increase the viability of H9c2 cardiomyocytes that suffered H/R. Both Hoechst33342 staining and FACS confirmed that Que could remarkably suppress the H/R-induced apoptotic cardiomyocytes. In addition, Que significantly alleviated H/R-induced the phosphorylation of JNK and p38, which further increased Bcl-2 expression and inhibited the activation of Bax and caspase-3 directly or indirectly. In summary, our results imply that Que can induce cardioprotection by inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways and modulate the expression of Bcl-2 and Bax proteins that provides a new experimental foundation for myocardial ischemia disease therapy. PMID- 26680105 TI - Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy. AB - BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT) is an emerging therapy for refractory focal epilepsy. However, the most optimal target for stimulation has not been unambiguously described. OBJECTIVE: In the present study, we investigated the correlation between the stimulation site and outcome in order to define the optimal target for deep brain stimulation in refractory epilepsy. METHODS: The locations of 62 contacts used in 30 treatment attempts in 15 prospectively followed patients during a 5 year period were assessed. Treatment attempts were classified into responding and non-responding trials using seizure reduction and side effect profile as criteria. The locations of active contacts were calculated with respect to mid-commissural point and visible borders of ANT in 3T MRI (ANT-normalized coordinate system) aiming to minimize the confounding effect of individual variation in the location and size of the ANT. RESULTS: Contacts in successful treatment trials were located significantly more anterior and superior both in AC-PC and ANT-normalized coordinate systems. Favourable outcome was observed at 3T MRI based location of ANT but not at location predicted by Schaltenbrandt atlas sagittal data. Contacts used in successful trials were at anterior aspect of the ANT complex evidenced by the ANT-normalized coordinate system. CONCLUSION: The anti-epileptic effect of anterior thalamic DBS may be dependent on stimulation site especially in the anterior to posterior axis. Extensive anatomical variation confounds severely the targeting of ANT. Therefore, direct visualization of the desired target for stimulation is essential for favourable outcome in refractory epilepsy. PMID- 26680106 TI - [Attitudes and experiences of off-label prescribing among paediatricians in a French university teaching hospital]. AB - PURPOSE: The lack of drugs specifically assessed for paediatric use results in a widespread off-label drug use. The aim of this work is to identify experiences and attitudes towards paediatrics off-label prescribing in a university teaching paediatric hospital. METHODS: A questionnaire of 24 items was sent by email to 409 paediatricians in February 2013. DATA COLLECTED: frequency of off-label prescribing, sources of information, concern about safety and adverse events with off-label drug use, proportion of parents informed and order with "off-label" mention. RESULTS: Eighty questionnaires were returned. Over 81% of responders were familiar with the concept of off-label drugs prescribing. The most common reason given for off-label prescribing was for a younger age (74%) and for another indication (28%). They (79%) used a colleague's opinion and the most important sources of information used were the literature (72%), international guidelines (62%), the French National Formulary Vidal (56%) and national guidelines (46%). Although 54% of responders expressed concerns about safety about off-label prescription, only 29% had observed adverse event with off-label drug use. Two third of respondents informed the parents but off-label prescribing cannot be always explained to family. Many respondents (81%) did not write "off label" mention on prescription. However, 52% stated that they would be willing to undertake off-label prescription monitoring with a local observatory. CONCLUSION: Our study describes the perceptions and attitudes of paediatrician's regarding off-label prescribing for children. Patient information and documentation in the patient file remain incomplete. The prospective collection of off-label prescription will locally be performed. PMID- 26680107 TI - Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice. AB - Obesity is one of several factors implicated in chronic kidney disease (CKD). Thymol, a monoterpene phenolic compound found in the oils of thyme with multiple biological properties especially antidiabetic activity. The present study was undertaken to evaluate the thymol against diabetic nephropathy by high fat diet (HFD)-induced diabetic C57BL/6J mice. After 10 weeks of continuous dietary intervention, HFD (fat- 35.2%) to mice presented characteristic features of progressive nephropathy by significant increased in kidney weight, blood, and urinary parameters, glomerulosclerosis, oxidative stress, hyperlipidemia and subsequent renal injuries. After intragastric administration of thymol (40 mg/kg BW) daily for the subsequent 5 weeks significantly decreased the blood, urinary parameters and kidney weight. Thymol inhibited the activation of transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF). Also, significantly increased the antioxidants and suppresses the lipid peroxidation markers in erythrocytes and kidney tissue compared to the diabetic mice. Thymol downregulated the expression level of sterol regulatory element binding protein-1c (SREBP-1c) and reduced the lipid accumulation in renal. Histopathological study of kidney tissues showed that extracellular mesangial matrix expansion, glomerulosclerosis in diabetic mice were suppressed by thymol. Further, our results indicate that administration of thymol afforded remarkable protection against HFD-induced diabetic nephropathy. PMID- 26680108 TI - Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress. AB - Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross-talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM-A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose-6-phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26680109 TI - Channel-forming activity of syringopeptin 25A in mercury-supported lipid bilayers with a phosphatidylcholine distal leaflet. AB - The channel-forming activity of the lipodepsipeptide syringopeptin 25A (SP25A) was investigated at a tethered bilayer lipid membrane (tBLM) with a dioleoylphosphatidylcholine distal leaflet, anchored to a mercury electrode through a hydrophilic tetraethyleneoxy spacer. SP25A was incorporated in the tBLM from different aqueous solutions by recording a series of impedance spectra over a potential range encompassing non-physiological transmembrane potential (Deltaphi) values. Once incorporated, SP25A forms stable ion channels over the narrower range of physiological Deltaphi values. Ion flow into and out of the spacer, through the lipid bilayer moiety of the tBLM, was monitored by potential step chronocoulometry and cyclic voltammetry at pH3, 5.4 and 6.8. Potassium ion flow into the hydrophilic spacer along the SP25A channels, during the negative potential scan, proceeds in two stages, except at the higher pH and lower SP25A concentration adopted, where it proceeds in a single stage. In light of the behavior of SP25A single channel currents reported in the literature, the first stage is ascribed to large channels resulting from the aggregation of small ones, while the second more negative stage is associated with the small channels resulting from the disaggregation of the large ones. PMID- 26680110 TI - SnO2 Quantum Dots@Graphene Oxide as a High-Rate and Long-Life Anode Material for Lithium-Ion Batteries. AB - Tin-based electrode s offer high theoretical capacities in lithium ion batteries, but further commercialization is strongly hindered by the poor cycling stability. An in situ reduction method is developed to synthesize SnO2 quantum dots@graphene oxide. This approach is achieved by the oxidation of Sn(2+) and the reduction of the graphene oxide. At 2 A g(-1), a capacity retention of 86% is obtained even after 2000 cycles. PMID- 26680111 TI - Issues in biomarker identification, validation and development for disease diagnostics in Public Health. PMID- 26680112 TI - Quantitative assay of capreomycin oleate levels in a drug formulation for inhalation with a fully validated HPLC method. AB - Capreomycin sulfate (CS), a mixture of 4 closely related compounds (powder mainly comprised of 2 forms), commonly injected intramuscularly is intended to be administer by inhalation for the treatment of pulmonary tuberculosis. In order to increase the drug residence time in the lung, capreomycin hydrophobicity was enhanced by substituting sulfate with oleate, thus obtaining capreomycin oleate (CO). The generation of a more hydrophobic ion-pair allows the reduction of the drug solubilisation in the bronchoalveolar fluids as well as its systemic absorption. The aim of the present study was to quantify CO in an in-house prepared drug formulation for inhalation. In this regard, a Hydrophilic Liquid Interaction Chromatography (HILIC) method was optimized with acetonitrile (ACN)/water containing eluents and a diol-type stationary phase. The optimal eluent composition [ACN/water-80/20 (v/v), 20mM ammonium formate, 3.0 wspH] produced a good separation (alpha equal to 1.15) between the two main peaks. The developed HILIC method succeeded in the quantitative assay of CO in the drug formulation and was fully validated. Very good precision and accuracy in the short- and long-period along with appreciably low LOD and LOQ values (respectively 1.75 and 5.25MUg/mL) turned out. PMID- 26680113 TI - The natural history of continuing improvement in an individual after a long period of impaired consciousness: The story of I.J. AB - AIM: Recovery of consciousness and recovery of function among patients with prolonged disorders of consciousness rarely occur. Those patients who do regain consciousness typically remain with severe disability. The aim of this retrospective study is to suggest that continuing improvement is possible in a survivor of catastrophic brain injury after being in a prolonged state of disordered consciousness. CASE STUDY: This retrospective single case study follows the progress of a 29 year old man, I.J, who sustained a severe traumatic brain injury following an assault in October 2011. He was in a vegetative state for 15 months and in a minimally conscious state for a further 4 months. This was followed by a slow and steady recovery of motor and cognitive functions. At 3 years post-injury I.J is considered to be moderately disabled. He is now living in the community with continuing outpatient support. On the disability rating scale his level of functioning is rated as mildly dependent. CONCLUSION: This study shows that continuing recovery to a level of moderate disability is possible, even after a prolonged disorder of consciousness. Intense multi disciplinary long-term rehabilitation and cranioplasty may be contributing factors for such an unexpected recovery. PMID- 26680114 TI - Stereotactic radiosurgery alone for limited brain metastases: are we ready for prime time? PMID- 26680115 TI - Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of regenerative medicine. PMID- 26680116 TI - Sampling mobile oceanic fishes and sharks: implications for fisheries and conservation planning. AB - Tuna, billfish, and oceanic sharks [hereafter referred to as 'mobile oceanic fishes and sharks' (MOFS)] are characterised by conservative life-history strategies and highly migratory behaviour across large, transnational ranges. Intense exploitation over the past 65 years by a rapidly expanding high-seas fishing fleet has left many populations depleted, with consequences at the ecosystem level due to top-down control and trophic cascades. Despite increases in both CITES and IUCN Red Listings, the demographic trajectories of oceanic sharks and billfish are poorly quantified and resolved at geographic and population levels. Amongst MOFS trajectories, those of tunas are generally considered better understood, yet several populations remain either overfished or of unknown status. MOFS population trends and declines therefore remain contentious, partly due to challenges in deriving accurate abundance and biomass indices. Two major management strategies are currently recognised to address conservation issues surrounding MOFS: (i) internationally ratified legal frameworks and their associated regional fisheries management organisations (RFMOs); and (ii) spatio-temporal fishery closures, including no-take marine protected areas (MPAs). In this context, we first review fishery-dependent studies relying on data derived from catch records and from material accessible through fishing extraction, under the umbrella of RFMO-administrated management. Challenges in interpreting catch statistics notwithstanding, we find that fishery dependent studies have enhanced the accuracy of biomass indices and the management strategies they inform, by addressing biases in reporting and non random effort, and predicting drivers of spatial variability across meso- and oceanic scales in order to inform stock assessments. By contrast and motivated by the increase in global MPA coverage restricting extractive activities, we then detail ways in which fishery-independent methods are increasingly improving and steering management by exploring facets of MOFS ecology thus far poorly grasped. Advances in telemetry are increasingly used to explore ontogenic and seasonal movements, and provide means to consider MOFS migration corridors and residency patterns. The characterisation of trophic relationships and prey distribution through biochemical analysis and hydro-acoustics surveys has enabled the tracking of dietary shifts and mapping of high-quality foraging grounds. We conclude that while a scientific framework is available to inform initial design and subsequent implementation of MPAs, there is a shortage in the capacity to answer basic but critical questions about MOFS ecology (who, when, where?) required to track populations non-extractively, thereby presenting a barrier to assessing empirically the performance of MPA-based management for MOFS. This sampling gap is exacerbated by the increased establishment of large (>10000 km2 ) and very large MPAs (VLMPAs, >100000 km2 ) - great expanses of ocean lacking effective monitoring strategies and survey regimes appropriate to those scales. To address this shortcoming, we demonstrate the use of a non-extractive protocol to measure MOFS population recovery and MPA efficiency. We further identify technological avenues for monitoring at the VLMPA scale, through the use of spotter planes, drones, satellite technology, and horizontal acoustics, and highlight their relevance to the ecosystem-based framework of MOFS management. PMID- 26680117 TI - Disease causing homozygous variants in the human hairless gene. AB - BACKGROUND: Atrichia with papular lesions (APL) is a rare irreversible form of complete hair loss inherited in autosomal recessive manner. Hair loss is often followed by the appearance of multiple keratin-filled cysts or papules on exterior parts of the body. This phenotype results due to mutations in the human hairless gene (HR) mapped on chromosome 8p21.3. The present study was aimed to search for disease-causing sequence variants in the HR gene in five consanguineous families exhibiting features of APL. METHODS: Linkage in five Pakistani lineal consanguineous families, displaying features of APL, was tested using microsatellite markers flanking the HR gene on chromosome 8p21.3. After constructing the haplotypes, variants in the gene HR were searched by dideoxy chain termination sequencing. RESULTS: Haplotype analysis established linkage in all five families to the HR gene located on chromosome 8p.21.3. Subsequently, sequencing HR identified a novel homozygous nonsense variant (c.2541G>A, p.Trp847*) in one and previously reported two pathogenic variants (p.Cys690*, p.Pro1157Arg) in the other four families. CONCLUSION: Mutations identified extend the spectrum of mutations in the HR gene resulting in APL. Characterizing the clinical spectrum resulting from the disease-causing homozygous variants in the HR gene will direct clinical care of the family members. PMID- 26680129 TI - Real-Time TD-DFT with Classical Ion Dynamics: Methodology and Applications. AB - We present a method for real-time propagation of electronic wave functions, within time-dependent density functional theory (RT-TDDFT), coupled to ionic motion through mean-field classical dynamics. The goal of our method is to treat large systems and complex processes, in particular photocatalytic reactions and electron transfer events on surfaces and thin films. Due to the complexity of these processes, computational approaches are needed to provide insight into the underlying physical mechanisms and are therefore crucial for the rational design of new materials. Because of the short time step required for electron propagation (of order ~10 attoseconds), these simulations are computationally very demanding. Our methodology is based on numerical atomic-orbital-basis sets for computational efficiency. In the computational package, to which we refer as TDAP-2.0 (Time-evolving Deterministic Atom Propagator), we have implemented a number of important features and analysis tools for more accurate and efficient treatment of large, complex systems and time scales that reach into a fraction of a picosecond. We showcase the capabilities of our method using four different examples: (i) photodissociation into radicals of opposite spin, (ii) hydrogen adsorption on aluminum surfaces, (iii) optical absorption of spin-polarized organic molecule containing a metal ion, and (iv) electron transfer in a prototypical dye-sensitized solar cell. PMID- 26680130 TI - Hotspots and social background of urban traffic crashes: A case study in Cluj Napoca (Romania). AB - Mobility practices have changed dramatically in Romanian towns over the last 25 years, following the collapse of socialist mobility restrictions. Urban areas like Cluj-Napoca are facing both increasing immigration and car mobility, and therefore increasing levels of road traffic crashes. The analysis of traffic crashes is one of the most important elements for improving the road safety policy. This paper is divided in two parts. In the first one, the authors focus on identifying the traffic crash hotspots along the street network, while in the second part they discuss the social background of road traffic crash occurrence. The first step in analyzing traffic crashes is to determine crash hotspots. A four-year record (2010-2013) provided by the Traffic Department of the General Inspectorate of Romanian Police (GIRPTD) was used. As a method of hotspot determination, the Kernel Density Estimation tool was employed, in the frame of the spatial analysis along network (SANET). The outcome was the hotspot map of traffic crashes in Cluj-Napoca. The results have revealed 4 categories of street segments: not-dangerous, low-dangerous, medium-dangerous and high-dangerous. Based on this classification, at least 4 dangerous areas were identified, located at the city entrances-exits (in the West, North-West and East) and the city center (the most dangerous zone). The second part of the paper focuses on social groups involved in car crashes. The following are considered: age, gender and blood alcohol concentration of the person (driver or pedestrian) found guilty for every individual crash. PMID- 26680131 TI - Mesocosms Reveal Ecological Surprises from Climate Change. AB - Understanding, predicting, and mitigating the impacts of climate change on biodiversity poses one of the most crucial challenges this century. Currently, we know more about how future climates are likely to shift across the globe than about how species will respond to these changes. Two recent studies show how mesocosm experiments can hasten understanding of the ecological consequences of climate change on species' extinction risk, community structure, and ecosystem functions. Using a large-scale terrestrial warming experiment, Bestion et al. provide the first direct evidence that future global warming can increase extinction risk for temperate ectotherms. Using aquatic mesocosms, Yvon-Durocher et al. show that human-induced climate change could, in some cases, actually enhance the diversity of local communities, increasing productivity. Blending these theoretical and empirical results with computational models will improve forecasts of biodiversity loss and altered ecosystem processes due to climate change. PMID- 26680132 TI - Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation. AB - BACKGROUND: We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA) mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline. METHODS: Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis. RESULTS: The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699). CONCLUSION: Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion. PMID- 26680133 TI - Selective inhibition of histone deacetylase 6 promotes survival in a rat model of hemorrhagic shock. AB - BACKGROUND: Hemorrhage is the leading cause of preventable trauma-related deaths. We have previously shown that treatment with Tubastatin A (Tub A), a histone deacetylase 6 (HDAC6) inhibitor, can improve survival in a rodent model of septic shock. The aims of the present study were to determine whether selective inhibition of HDAC6 can promote survival in a model of hemorrhagic shock (HS). METHODS: In Experiment I (survival study), Wistar-Kyoto rats were subjected to HS (55% volume blood loss), followed by intraperitoneal injection of either Tub A (70 mg/kg) dissolved in dimethyl sulfoxide (DMSO) or DMSO only (vehicle group) (n = 8 per group). Survival was monitored for 24 hours. In Experiment II (physiologic study), rats were subjected to a sublethal HS (40% blood loss), followed by the same treatment with Tub A (treatment group) or DMSO only (vehicle group, n = 5 per group). All animals were sacrificed 6 hours after hemorrhage, and the heart and liver tissues were harvested. Sham animals were not subjected to hemorrhage and treatment (sham group, n = 5 per group). Cardiac mitochondria were isolated to study the pyruvate dehydrogenase (PDH, an essential enzyme for adenosine triphosphate production) activity. Liver tissue lysates were analyzed for markers of apoptosis (cytochrome c, cleaved caspase 3) and inflammation (high mobility group box 1) by Western blotting. RESULTS: Severe HS (55% blood loss) was associated with 75% mortality, which was significantly improved by Tub A treatment (37.5% mortality in 24 hours, p = 0.048). Tub A also significantly enhanced the cardiac PDH activity compared with the vehicle group, while suppressing the hepatic high-mobility group box 1 expression, cytochrome c release, and caspase 3 activation. CONCLUSION: Our study has demonstrated for the first time that selective inhibition of HDAC6 can improve survival in a rodent model of HS. The potential mechanisms include enhanced PDH activity, decreased inflammatory drive, and attenuated cellular apoptosis. PMID- 26680134 TI - Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock. AB - BACKGROUND: Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In a nonsurvival model of TBI + HS, addition of high-dose valproic acid (VPA) (300 mg/kg) to hetastarch reduced brain lesion size and associated swelling 6 hours after injury; whether this would have translated into better neurologic outcomes remains unknown. It is also unclear whether lower doses of VPA would be neuroprotective. We hypothesized that addition of low-dose VPA to normal saline (NS) resuscitation would result in improved long-term neurologic recovery and decreased brain lesion size. METHODS: TBI was created in anesthetized swine (40-43 kg) by controlled cortical impact, and volume controlled hemorrhage (40% volume) was induced concurrently. After 2 hours of shock, animals were randomized (n = 5 per group) to NS (3* shed blood) or NS + VPA (150 mg/kg). Six hours after resuscitation, packed red blood cells were transfused, and animals were recovered. Peripheral blood mononuclear cells were analyzed for acetylated histone-H3 at lysine-9. A Neurological Severity Score (NSS) was assessed daily for 30 days. Brain magnetic resonance imaging was performed on Days 3 and 10. Cognitive performance was assessed by training animals to retrieve food from color-coded boxes. RESULTS: There was a significant increase in histone acetylation in the NS + VPA-treated animals compared with NS treatment. The NS + VPA group demonstrated significantly decreased neurologic impairment and faster speed of recovery as well as smaller brain lesion size compared with the NS group. Although the final cognitive function scores were similar between the groups, the VPA-treated animals reached the goal significantly faster than the NS controls. CONCLUSION: In this long-term survival model of TBI + HS, addition of low-dose VPA to saline resuscitation resulted in attenuated neurologic impairment, faster neurologic recovery, smaller brain lesion size, and a quicker normalization of cognitive functions. PMID- 26680136 TI - Resuscitative endovascular balloon occlusion of the aorta (REBOA): Comparison with immediate transfusion following massive hemorrhage in swine. AB - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is less invasive than emergency department thoracotomy for the treatment of massive hemorrhage. We evaluated the effects of REBOA on carotid blood flow (Qcarotid) in a porcine model of massive hemorrhage. We hypothesized that REBOA restores Qcarotid faster than reinfusion of blood. METHODS: Spontaneously breathing sedated Sinclair pigs underwent exponential hemorrhage of 65% total blood volume in 1 hour. They were randomized into three groups. Positive control (PC, n = 7) underwent immediate transfusion of shed blood. REBOA (n = 21) received a novel 7 Fr ER-REBOA catheter (Pryor Medical, Arvada, CO) placed into aortic Zone 1 via a femoral artery introducer for 30 minutes or 60 minutes, with transfusion either after deflation or midway through inflation. Negative control (n = 7) received no resuscitation. Qcarotid was recorded continuously using an ultrasonic flow probe. Survival and time between Qcarotid, min and both a stable maximal value (Qcarotid, max) and restoration of baseline flow (Qcarotid, new BL) were compared by Kaplan-Meier analysis. RESULTS: Median time to Qcarotid, max was 3.0 minutes in the REBOA group versus 9.6 minutes in the control group (p = 0.006). Median time to Qcarotid, new BL was 6.0 minutes in the REBOA group versus 20.5 minutes in the PC group (p = 0.11). Slope of the linear regression between Qcarotid, min and Qcarotid, new BL was 16.7 in REBOA and 10.4 in PC (p = 0.31). Four-hour survival was 95% (20 of 21) in the REBOA group versus 71% (5 of 7) in the PC group (p = 0.06) and 0% in the negative control group. CONCLUSION: REBOA resulted in the restoration of Qcarotid ("cerebrovascular resuscitation") at least as rapidly as retransfusion of shed blood, with equivalent 4-hour survival. Further studies of REBOA, to include mitigation of end-organ effects and longer follow up, are needed. PMID- 26680137 TI - Prehospital interventions in severely injured pediatric patients: Rethinking the ABCs. AB - BACKGROUND: The current conflict in Afghanistan has resulted in a high volume of significantly injured pediatric patients. The austere environment has demanded emphasis on prehospital interventions (PHIs) to sustain casualties during transport. METHODS: The Department of Defense Trauma Registry was queried for all pediatric patients (<=18 years) treated at Camp Bastion from 2004 to 2012. PHIs were grouped by Advanced Trauma Life Support categories into (1) airway (A)- intubation or surgical airway; 2) breathing (B)--chest tube or needle thoracostomy; and 3) circulation (C)--tourniquet or hemostatic dressing. Outcomes were assessed based on injury severity, hemodynamics, blood products and fluids, as well as mortality rates. RESULTS: There were 766 injured children identified with 20% requiring one or more PHIs, most commonly circulation (C, 51%) followed by airway (A, 40%) and breathing (B, 8.7%). The majority of C interventions were tourniquets (85%) and hemostatic dressings (15%). Only 38% of patients with extremity vascular injury or amputation received a C intervention, with a significant reduction in blood products and intravenous fluids associated with receiving a C PHI (both p < 0.05). A interventions consisted of endotracheal intubation for depressed mental status (Glasgow Coma Scale [GCS] score < 8). Among patients with traumatic brain injury, A interventions were associated with higher unadjusted mortality (56% vs. 20%, p < 0.01) and remained independently associated with increased mortality after multivariate adjustment (odds ratio, 5.9; p = 0.001). B interventions were uncommon and performed in only 2% of patients with no recorded adverse outcomes. CONCLUSION: There is a high incidence of PHIs among pediatric patients with severe wartime injuries. The most common and effective were C PHI for hemorrhage control, which should remain a primary focus of equipment and training. A interventions were most commonly performed in the setting of severe traumatic brain injury but were associated with worse outcomes. B interventions seem safe and effective and may be underused. LEVEL OF EVIDENCE: Care management/therapeutic study, level IV. PMID- 26680135 TI - Recursive partitioning identifies greater than 4 U of packed red blood cells per hour as an improved massive transfusion definition. AB - BACKGROUND: Massive transfusion (MT) is classically defined as greater than 10 U of packed red blood cells (PRBCs) in 24 hours. This fails to capture the most severely injured patients. Extending the previous work of Savage and Rahbar, a rolling hourly rate-based definition of MT may more accurately define critically injured patients requiring early, aggressive resuscitation. METHODS: The Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) trial collected data from 10 Level 1 trauma centers. Patients were placed into rate based transfusion groups by maximal number of PRBCs transfused in any hour within the first 6 hours. A nonparametric analysis using classification trees partitioned data according to mortality at 24 hours using a predictor variable of maximum number PRBC units transfused in an hour. Dichotomous variables significant in previous scores and models as predictors of MT were used to identify critically ill patients: a positive finding on Focused Assessment with Sonography in Trauma (FAST) examination, Glasgow Coma Scale (GCS) score less than 8, heart rate greater than 120 beats/min, systolic blood pressure less than 90 mm Hg, penetrating mechanism of injury, international normalized ratio greater than 1.5, hemoglobin less than 11, and base deficit greater than 5. These critical indicators were then compared among the nodes of the classification tree. Patients omitted included those who did not receive PRBCs (n = 24) and those who did not have all eight critical indicators reported (n = 449). RESULTS: In a population of 1,245 patients, the classification tree included 772 patients. Analysis by recursive partitioning showed increased mortality among patients receiving greater than 13 U/h (73.9%, p < 0.01). In those patients receiving less than or equal to 13 U/h, mortality was greater in patients who received more than 4 U/h (16.7% vs. 6.0%, p < 0.01) (Fig. 1). Nodal analysis showed that the median number of critical indicators for each node was 3 (2-4) (<=4 U/h), 4 (3-5) (>4 U/h and <=13 U/h), and 5 (4-5.5) (>13 U/h). CONCLUSION: A rate-based transfusion definition identifies a difference in mortality in patients who receive greater than 4 U/h of PRBCs. Redefining MT to greater than 4 U/h allows early identification of patients with a significant mortality risk who may be missed by the current definition. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26680138 TI - Lack of utility of repeat monitoring of hemoglobin and hematocrit following blunt solid organ injury in children. AB - BACKGROUND: Current management protocols for children with blunt solid organ injury to the liver and spleen call for serial monitoring of the child's hemoglobin and hematocrit every 6, 12, or 24 hours, depending on the injury grade. We hypothesized that children who require emergent intervention in the form of laparotomy, angioembolization, or packed red blood cell (PRBC) transfusion because of bleeding from a solid organ injury will have changes in their vital signs that alert the clinician to the need for intervention, making scheduled laboratory evaluation unnecessary. METHODS: We performed a retrospective review of all children admitted to either of two pediatric trauma centers following blunt trauma with any grade liver or spleen injury from January 2009 to December 2013. Data evaluated include a need for intervention, indication for intervention, and timing of intervention. RESULTS: A total of 245 children were admitted with blunt liver or spleen injury. Six patients (2.5%) underwent emergent exploratory laparotomy for hypotension a median of 4 hours after injury (range, 2-4 hours), four of who required splenectomy. No child required laparotomy for delayed bleeding from a solid organ injury. One child (0.4%) underwent angioembolization for blunt splenic injury. Forty-one children (16.7%) received a PRBC transfusion during hospitalization, 32 of whom did not undergo laparotomy or angioembolization. Children who underwent an intervention had a lower nadir hematocrit (median, 22.9 vs. 32.8; p < 0.0001), longer time from injury to nadir hematocrit (median, 35.5 vs. 16 hours; p < 0.0001), and more total blood draws for hemoglobin and hematocrit monitoring (median, 20 vs. 5; p < 0.0001). CONCLUSION: Among children with blunt liver or spleen injury, a need for emergent intervention in the form of laparotomy or PRBC transfusion for hemorrhagic shock occurs within the first 24 hours of injury. Ongoing, scheduled monitoring of serum hemoglobin and hematocrit values may not be necessary. LEVEL OF EVIDENCE: Retrospective study with no negative criteria, prognostic study, level III. PMID- 26680139 TI - Dead or alive? New confirmatory test using quantitative analysis of computed tomographic angiography. AB - BACKGROUND: When clinical examination is not reliable for brain death (BD) diagnosis, the preferred confirmatory test at our institution is nuclear medicine perfusion test (NMPT). Computed tomographic angiography (CTA) has been described as an alternative for BD confirmation. This study was designed to quantitatively analyze CTA, assess its accuracy compared with NMPT, and define set parameters for BD confirmation. METHODS: This is a prospective clinical study, from 2007 to 2014, evaluating a consecutive series of clinically BD patients (n = 60) and randomly selected control group with normal CTA findings (n = 20). NMPT, used as the reference standard, was performed on all study patients followed immediately by CTA. Assessment of NMPT and quantitative CTA Hounsfield units of the horizontal segment of middle cerebral artery (M1), precommunicating segment of anterior cerebral artery (A1), and basilar artery (BA) was performed. RESULTS: In the study cohort, 88% demonstrated absence of cerebral blood flow (CBF) on NMPT; however, only 50% demonstrated absence on CTA. Together, 50% had no CBF on NMPT and CTA (Group 1), 38% had no CBF on NMPT but persistent CBF on CTA (Group 2), 12% had persistent CBF on both NMPT and CTA (Group 3). Analysis of variance demonstrated that all groups varied significantly for M1, A1, and BA (p < 0.001). We were able to establish criteria that differentiate persistent CBF on CTA as either preserved cerebral perfusion or stasis filling. CONCLUSION: We propose that a CTA Hounsfield units less than 80 in M1, A1, and BA is concordant with no CBF on NMPT, therefore indicative of a lack of physiologic cerebral perfusion, and thus allows the confirmation of BD with 97% sensitivity and 100% specificity. LEVEL OF EVIDENCE: Diagnostic study, level II. PMID- 26680140 TI - Sugar or salt? The relative roles of the glucocorticoid and mineralocorticoid axes in traumatic shock. AB - BACKGROUND: Glucocorticoid deficiency (GD) has been proposed as a key contributor to shock states, but the presence and role of acute mineralocorticoid deficiency may be of equal or greater significance. We sought to analyze the incidence and degree of acute mineralocorticoid deficiency and GD in an animal model of severe hemorrhage and shock. METHODS: Fifty-seven swine underwent 35% volume-controlled hemorrhage followed by aortic cross-clamping for 50 minutes to induce truncal ischemia-reperfusion. Protocol-guided resuscitation was performed. Laboratory analysis included cortisol, aldosterone, and plasma renin activity. The aldosterone-to-renin ratio (ARR) was calculated at each time point, and changes were correlated to markers of perfusion. RESULTS: Mean baseline cortisol levels were 5.8 MUg/dL. Following hemorrhage, there was a significant increase in mean cortisol to 9.2 MUg/dL (p < 0.001). After 1 hour of reperfusion, there was no change in mean cortisol levels (9.8 MUg/dL, p = 0.12). Mean baseline aldosterone was 13.3 pg/mL. Aldosterone levels before cross-clamp removal increased significantly to 115.1 pg/mL (p < 0.001) and then rapidly declined to 49.2 pg/mL (p < 0.001) after 1 hour of reperfusion. Conversely, baseline plasma renin activity was 0.75 ng/mL per hour and increased significantly before cross-clamp removal (1.8) and at 1 hour (8.9, both p < 0.001). The ARR at baseline was 96.1 and increased to 113.5 (p = 0.68) before cross-clamp removal but significantly declined following 1 hour of reperfusion to 7.6 (p < 0.001). Overall, this represented a 93% reduction in mean ARR following reperfusion. The degree of aldosterone deficiency correlated with degree of systemic shock as measured by arterial base deficit (r = 0.47, p = 0.04), while cortisol showed no correlation. CONCLUSION: Hemorrhagic shock with ischemia-reperfusion injury resulted in only modest impact on the glucocorticoid axis, but major dysfunction of the mineralocorticoid axis and severe hyperreninemic hypoaldosteronism. The degree of aldosterone deficiency may provide prognostic information or offer potential targets for pharmacologic intervention. LEVEL OF EVIDENCE: Diagnostic study, level III. PMID- 26680141 TI - The use of extracorporeal membrane oxygenation in blunt thoracic trauma: A study of the Extracorporeal Life Support Organization database. AB - BACKGROUND: Reports documenting the use of extracorporeal membrane oxygenation (ECMO) after blunt thoracic trauma are scarce. We used a large, multicenter database to examine outcomes when ECMO was used in treating patients with blunt thoracic trauma. METHODS: We performed a retrospective analysis of ECMO patients in the Extracorporeal Life Support Organization database between 1998 and 2014. The diagnostic code for blunt pulmonary contusion (861.21, DRG International Classification of Diseases-9th Rev.) was used to identify patients treated with ECMO after blunt thoracic trauma. Variations of pre-ECMO respiratory support were also evaluated. The primary outcome was survival to discharge; the secondary outcome was hemorrhagic complication associated with ECMO. RESULTS: Eighty-five patients met inclusion criteria. The mean +/- SEM age of the cohort was 28.9 +/- 1.1 years; 71 (83.5%) were male. The mean +/- SEM pre-ECMO PaO2/FIO2 ratio was 59.7 +/- 3.5, and the mean +/- SEM pre-ECMO length of ventilation was 94.7 +/- 13.2 hours. Pre-ECMO support included inhaled nitric oxide (15 patients, 17.6%), high-frequency oscillation (10, 11.8%), and vasopressor agents (57, 67.1%). The mean +/- SEM duration of ECMO was 207.4 +/- 23.8 hours, and 63 patients (74.1%) were treated with venovenous ECMO. Thirty-two patients (37.6%) underwent invasive procedures before ECMO, and 12 patients (14.1%) underwent invasive procedures while on ECMO. Hemorrhagic complications occurred in 25 cases (29.4%), including 12 patients (14.1%) with surgical site bleeding and 16 (18.8%) with cannula site bleeding (6 patients had both). The rate of survival to discharge was 74.1%. Multivariate analysis showed that shorter duration of ECMO and the use of venovenous ECMO predicted survival. CONCLUSION: Outcomes after the use of ECMO in blunt thoracic trauma can be favorable. Some trauma patients are appropriate candidates for this therapy. Further study may discern which subpopulations of trauma patients will benefit most from ECMO. LEVEL OF EVIDENCE: Therapeutic/care management study, level V. PMID- 26680142 TI - Hips don't lie: Waist-to-hip ratio in trauma patients. AB - BACKGROUND: Obesity measured by body mass index (BMI) is known to be associated with worse outcomes in trauma patients. Recent studies have assessed the impact of distribution of body fat measured by waist-hip ratio (WHR) on outcomes in nontrauma patients. The aim of this study was to assess the impact of distribution of body fat (WHR) on outcomes in trauma patients. METHODS: A 6-month (June to November 2013) prospective cohort analysis of all admitted trauma patients was performed at our Level 1 trauma center. WHR was measured in each patient on the first day of hospital admission. Patients were stratified into two groups: patients with WHR of 1 or greater and patients with WHR of less than 1. Outcome measures were complications and in-hospital mortality. Complications were defined as infectious, pulmonary, and renal complications. Regression and correlation analyses were performed. RESULTS: A total of 240 patients were enrolled, of which 28.8% patients (n = 69) had WHR of 1 or greater. WHR had a weak correlation with BMI (R = 0.231, R = 0.481). Eighteen percent (n = 43) of the patients developed complications, and the mortality rate was 10% (n = 24). Patients with a WHR of 1 or greater were more likely to develop in-hospital complications (32% vs. 13%, p = 0.001) and had a higher mortality rate (24% vs. 4%, p = 0.001) compared with the patients with a WHR of less than 1. In multivariate analysis, a WHR of 1 or greater was an independent predictor for the development of complications (odds ratio, 3.1; 95% confidence interval 1.08-9.2; p = 0.03) and mortality (odds ratio, 13.1; 95% confidence interval, 1.1-70; p = 0.04). CONCLUSION: Distribution of body fat as measured by WHR independently predicts mortality and complications in trauma patients. WHR is better than BMI in predicting adverse outcomes in trauma patients. Assessing the fat distribution pattern in trauma patients may help improve patient outcomes through focused targeted intervention. LEVEL OF EVIDENCE: Prognostic study, level II. PMID- 26680143 TI - Geriatric trauma G-60 falls with hip fractures: A pilot study of acute pain management using femoral nerve fascia iliac blocks. AB - BACKGROUND: Hip fractures due to falls cause significant morbidity and mortality among geriatric patients. A significant unmet need is an optimal pain management strategy. Consequently, patients are treated with standard analgesic care (SAC) regimens, which deliver high narcotic doses. However, narcotics are associated with delirium as well as gastrointestinal and respiratory failure risks. The purpose of this pilot study was to determine the safety and effectiveness of ultrasound-guided continuous compartmental fascia iliaca block (CFIB) in patients 60 years or older with hip fractures in comparison with SAC alone. METHODS: We performed a retrospective study of 108 patients 60 years or older, with acute pain secondary to hip fracture (2012-2013). Patient variables were age, sex, comorbidities, and Injury Severity Score (ISS). Primary outcome was pain scores; secondary outcomes included hospital length of stay, discharge disposition, morbidity, and mortality. Statistical analysis was performed using (IBM SPSS version 22). For group comparison (SAC vs. SAC + CFIB) median test, repeated measures analysis and Student's t test of transformed pain scores were used. RESULTS: Sixty-four patients received SAC only, and 44 patients received SAC + CFIB. Each CFIB placement was successful on first attempt without complications. Median time from emergency department arrival to block placement was 12.5 hours (interquartile range, 4-22 hours). Patients who received SAC + CFIB had significantly lower pain score ratings than patients treated with SAC alone. There were no differences in inpatient morbidity and mortality rates. Patients treated with SAC + CFIB were discharged home more often (p < 0.05). CONCLUSION: Ultrasound-guided CFIB is safe, practical, and readily integrated into the G-60 service for improved pain management of hip fractures. We are now conducting a prospective randomized control trial to confirm our observations. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26680144 TI - Western Trauma Association Critical Decisions in Trauma: Management of abdominal vascular trauma. PMID- 26680145 TI - Western Trauma Association Critical Decisions in Trauma: Diagnosis and management of esophageal injuries. AB - This is a recommended management algorithm from the Western Trauma Association addressing the diagnostic evaluation and management of esophageal injuries in adult patients. Because there is a paucity of published prospective randomized clinical trials that have generated Class I data, the recommendations herein are based primarily on published observational studies and expert opinion of Western Trauma Association members. The algorithms and accompanying comments represent a safe and sensible approach that can be followed at most trauma centers. We recognize that there will be patient, personnel, institutional, and situational factors that may warrant or require deviation from the recommended algorithm. We encourage institutions to use this guideline to formulate their own local protocols.The algorithm contains letters at decision points; the corresponding paragraphs in the text elaborate on the thought process and cite pertinent literature. The annotated algorithm is intended to (a) serve as a quick bedside reference for clinicians; (b) foster more detailed patient care protocols that will allow for prospective data collection and analysis to identify best practices; and (c) generate research projects to answer specific questions concerning decision making in the management of adults with esophageal injuries. PMID- 26680146 TI - Western Trauma Association Critical Decisions in Trauma: Diagnosis and management of duodenal injuries. PMID- 26680147 TI - Erwin R. Thal, MD (1936-2014). PMID- 26680150 TI - Cognitive function and disability in late life: an ecological validation of the 10/66 battery of cognitive tests among community-dwelling older adults in South India. AB - BACKGROUND: The 10/66 Dementia Research Group developed and validated a culture and education fair battery of cognitive tests for diagnosis of dementia in population-based studies in low-income and middle-income countries including India. AIMS: This study examined the association between individual domains of the 10/66 battery of cognitive tests and 'disability' and 'functional impairment' in community-dwelling older adults in South India. METHODS: One hundred twenty nine adults aged 60-90 years residing in Karunapura, in the city of Mysore, were interviewed in their own homes. Cognitive functioning was measured by administering the 10/66 battery of cognitive tests that composes of Community Screening Instrument for Dementia (CSI'D' COGSCORE), verbal fluency (VF) and word list memory recall (WLMR). A reliable informant was interviewed to ascertain if the subject's cognitive problems have resulted in functional impairment. Disability was measured by WHO Disability Schedule-II (DAS). RESULTS: The women had significantly lower CSI'D' COGSCORE score when compared with men (p = 0.002). The presence of 'functional impairment' resulting from cognitive decline was significantly associated with lower scores on VF (p = 0.03), WLMR (p = 0.03) and CSI'D' COGSCOREs (p < 0.01). There was a significant inverse association between WHO DAS II score and WLMR (p = 0.004), VF (0.006) and CSI'D' COGSCORE scores (p <= 0.001) even after adjusting for self-reported ischaemic heart disease, stroke, chronic obstructive airway disease, hypertension and diabetes. CONCLUSIONS: Lower scores on individual domains of the 10/66 battery of cognitive tests are associated with higher levels of disability and functional impairment in community-dwelling older adults. These culture and education fair tests are suitable for use in population-based research in India. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26680151 TI - Postpartum depression and brain response to infants: Differential amygdala response and connectivity. AB - Recent evidence suggests that postpartum depression is associated with reduced amygdala (AMY) response to negative stimuli. However, given the anhedonic features of PPD, it is important to consider mothers' brain response specifically to positive infant and to other positive stimuli. Mothers with (n = 28) and without (n = 17) clinically determined PPD (n = 28) viewed smiling pictures of infants (Own and Other), and positive non-infant stimuli (Non-Infant). First, we examined group differences in AMY response across conditions. Next, psychophysiological interaction was used to examine group differences in AMY connectivity across conditions. Connectivity estimates were then correlated with measures of maternal mood and anxiety. PPD mothers, compared to non-PPD mothers, showed overall increased AMY response across conditions in the right AMY. Despite this, PPD mothers demonstrated decreased bilateral AMY-right insular cortex (IC) connectivity as compared to non-PPD mothers when they view Own-Other infants. Furthermore, decreasing AMY-IC connectivity was associated with increasing symptoms of depression and anxiety. These differences were evident only for infant stimuli and did not apply to all positively valenced stimuli. Thus, PPD mothers show altered brain response and connectivity in regions strongly implicated in the processing of socially and emotionally relevant stimuli, as well as interoception and the evaluation of subjective emotional experience. PMID- 26680152 TI - Community-wide changes in intertaxonomic temporal co-occurrence resulting from phenological shifts. AB - Global climate change is known to affect the assembly of ecological communities by altering species' spatial distribution patterns, but little is known about how climate change may affect community assembly by changing species' temporal co occurrence patterns, which is highly likely given the widely observed phenological shifts associated with climate change. Here, we analyzed a 29-year phenological data set comprising community-level information on the timing and span of temporal occurrence in 11 seasonally occurring animal taxon groups from 329 local meteorological observatories across China. We show that widespread shifts in phenology have resulted in community-wide changes in the temporal overlap between taxa that are dominated by extensions, and that these changes are largely due to taxa's altered span of temporal occurrence rather than the degree of synchrony in phenological shifts. Importantly, our findings also suggest that climate change may have led to less phenological mismatch than generally presumed, and that the context under which to discuss the ecological consequences of phenological shifts should be expanded beyond asynchronous shifts. PMID- 26680154 TI - Angiographic Anatomy of External Iliac Arteries in the Sheep. AB - External iliac artery atherosclerotic disease and aneurism occur in man. For treatment, imaging is required to facilitate minimally invasive introduction and advancement of stents within the intended vessels. Sheep are commonly used to test and improve stents. However, little information is published regarding the angiographic anatomy of the iliac arteries in the ovine species. The objective of this study was to describe the angiographic anatomy of the iliac arteries in the sheep. Computed tomography (CT) angiography and gross anatomical dissection were performed in, respectively, 10 and 43 adult ewes. Diameters and lengths of the arteries were measured. In comparison with man, salient anatomical differences were identified in the sheep: (1) the absence of common iliac arteries, (2) the common trunk at the origin of internal iliac arteries and (3) the location of the bifurcation of the external iliac arteries into femoral arteries in the pelvis (not in the limb). External iliac arteries in this series of sheep were 86 mm long in average and had a mean diameter of 7.5 mm. Lengths of arteries are only slightly different between man and sheep, while diameters are rather similar. Therefore, the sheep model appears to be sufficiently similar to man to test stent properties. This study provides useful reference images and measures of lengths and diameters of relevant arteries that could be applied to research with ovine models. PMID- 26680153 TI - Staphylococcus aureus forms spreading dendrites that have characteristics of active motility. AB - Staphylococcus aureus is historically regarded as a non-motile organism. More recently it has been shown that S. aureus can passively move across agar surfaces in a process called spreading. We re-analysed spreading motility using a modified assay and focused on observing the formation of dendrites: branching structures that emerge from the central colony. We discovered that S. aureus can spread across the surface of media in structures that we term 'comets', which advance outwards and precede the formation of dendrites. We observed comets in a diverse selection of S. aureus isolates and they exhibit the following behaviours: (1) They consist of phenotypically distinct cores of cells that move forward and seed other S. aureus cells behind them forming a comet 'tail'; (2) they move when other cells in the comet tail have stopped moving; (3) the comet core is held together by a matrix of slime; and (4) the comets etch trails in the agar as they move forwards. Comets are not consistent with spreading motility or other forms of passive motility. Comet behaviour does share many similarities with a form of active motility known as gliding. Our observations therefore suggest that S. aureus is actively motile under certain conditions. PMID- 26680155 TI - Assessment of postoperative short-term and long-term mortality risk in Chinese geriatric patients for hip fracture using the Charlson comorbidity score. AB - INTRODUCTION: The clinical outcome of geriatric patients with hip fracture depends on surgical management as well as other medical factors. This study aimed to evaluate the relationship between Charlson comorbidity score and in-patient, 30-day, and 1-year mortality in Chinese geriatric patients who underwent surgery for hip fracture. METHODS: This was a historical cohort study conducted in a tertiary trauma referral centre in Hong Kong. From 1 January 2009 to 31 December 2010, 759 operated hip fracture patients who were over 65 years were recruited. The Charlson Comorbidity Index of each patient was retrieved from their medical records. The total Charlson comorbidity score, the highest Charlson comorbidity score, and the Charlson comorbidity score were calculated. The associations between these scores and in-patient, 30-day, and 1-year mortality were examined using Mann-Whitney U test and Cox regression model. RESULTS: The mean in-patient, 30-day, and 1-year mortality rate was 0.8%, 2.5%, and 16.3%, respectively. The total Charlson comorbidity score was significantly associated with in-patient mortality (P=0.031). The total Charlson comorbidity score (P<0.001) and Charlson comorbidity score (P=0.010) were significantly associated with 30-day mortality. All three scores were also significantly related to 1-year mortality (P<0.001). A Cox regression model demonstrated the relationship between total Charlson comorbidity score and 30-day and 1-year mortality. This can help predict 30-day and 1-year mortality risk in geriatric patients admitted for hip fracture surgery. CONCLUSION: The Charlson comorbidity score provides a good preoperative indicator of 30-day and 1-year mortality in geriatric patients with hip fracture. PMID- 26680156 TI - Prevalence of pre-sarcopenia and sarcopenia in Hong Kong Chinese geriatric patients with hip fracture and its correlation with different factors. AB - INTRODUCTION: Sarcopenia and osteoporosis are age-related declines in the quantity of muscle and bone, respectively. Both contribute in disability, fall, and hip fracture in the elderly. This study reported the prevalence of sarcopenia in Chinese geriatric patients with hip fracture, and the correlation between relative appendicular skeletal muscle mass index and other factors. METHODS: This case series was conducted in Kowloon West Cluster Orthopaedic Rehabilitation Centre in Hong Kong. Data of all geriatric patients with primary hip fracture admitted to the above Centre from June to December 2014 were studied. Isometric grip strength, the maximal handgrip strength, was measured using a JAMAR hand dynamometer. Body composition including appendicular and whole-body lean body mass was measured using dual-energy X-ray absorptiometry. Pearson's correlation was used to examine the correlation between relative appendicular skeletal muscle mass index and other factors. RESULTS: A total of 239 patients with a mean age of 82 years were included in the study. Stratifying patients as male or female, the mean (+/- standard deviation) hand grip strength was 20.6 +/- 7.3 kg and 13.6 +/- 4.5 kg, the mean relative appendicular skeletal muscle mass index was 5.72 +/- 0.83 kg/m(2) and 4.87 +/- 0.83 kg/m(2), and the mean hip bone mineral density was 0.696 +/- 0.13 g/cm(2) and 0.622 +/- 0.12 g/cm(2), respectively. The prevalence of sarcopenia based on relative appendicular skeletal muscle mass index and hand grip strength according to the Asian Working Group for Sarcopenia definition was 73.6% in males and 67.7% in females. According to the European Working Group on Sarcopenia definition, the prevalence of pre-sarcopenia was 20.8% in males and 12.4% in females. Relative appendicular skeletal muscle mass index was positively correlated with hand grip strength, body weight, hip bone mineral density, body mass index, and total fat mass in males; and hand grip strength, body weight, body height, body mass index, and total fat mass in females. Except for body height in females, all correlations were statistically significant. CONCLUSION: The prevalence of sarcopenia was very high in geriatric hip fracture patients, and much higher than that in community-dwelling elderly population. Apart from the need to prescribe osteoporosis medicine, sarcopenia screening and treatment should be offered and is essential to reduce subsequent fall, subsequent fracture, fracture-related complications and economic burden to Hong Kong. PMID- 26680157 TI - Synthesis of the aglycon of aspafiliosides E and F based on cascade reactions. AB - A synthesis of C17alpha-OH-tigogenin, the aglycon of aspafiliosides E and F, is described. The main features of the synthesis are three cascade processes, which involve the iodo-lactonization of furostan-26-acid to open ring E, a cascade hydrolysis/intramolecular SN2 process to close ring E, and a cascade intramolecular redox-ketalization process to close ring F. This synthesis would enrich the strategies used for the manipulation of spiroketals in steroidal sapogenins and other substrates. PMID- 26680158 TI - A simple and efficient method for cryopreservation and recovery of viable Plasmodium vivax and P. falciparum sporozoites. AB - Plasmodium falciparum and Plasmodium vivax sporozoites are the crucial stages of malaria parasites that initiate infection in humans. However, studies to develop new vaccines and drugs targeting these infective stages remain insufficient due to limited availability of sporozoites for research. This is a consequence of relatively few facilities that are established to produce sporozoites of human malaria parasites, sporozoites remaining viable for only a few days, and infected mosquitoes being a biohazard, making them difficult to transport. Cryopreservation of sporozoites offers the potential to alleviate these limitations and enhance sporozoite availability. These experiments were performed to evaluate methods for cryopreservation of P. vivax and P. falciparum sporozoites. Sporozoites, isolated in sterile buffer from infected mosquitoes by manual dissection of salivary glands, were cryopreserved using several types of commercially available serum-free cryoprotective solutions. The efficiency of cryopreservation was validated by a standard in vitro gliding motility assay as a measure of sporozoite activity. Viability of infective sporozoites was defined as percent gliding of sporozoites attached to the coverslip. Significant differences were observed among the cryopreservation media and protocols evaluated, with CryoStor CS2 giving the best results for both P. falciparum and P. vivax, whereas Hestar 200 worked efficiently only for P. vivax sporozoites. Further improvement in recovery of viable sporozoites would be anticipated using automated controlled rate freezing equipment. Our results demonstrate that cryopreservation provides an alternative for experimental studies that currently rely on fresh P. falciparum and P. vivax sporozoites. PMID- 26680159 TI - Morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5 trisphosphate receptor mRNA of Trypanosoma cruzi and suppresses parasite growth and infectivity. AB - Morpholino antisense oligos (MAOs) are used to investigate physiological gene function by inhibiting gene translation or construction of specific alternative splicing variants by blocking cis-splicing. MAOs are attractive drug candidates for viral- and bacterial-infectious disease therapy because of properties such as in vivo stability and specificity to target genes. Recently, we showed that phosphorothioate antisense oligos against Trypanosoma cruzi inositol 1,4,5 trisphosphate receptor (TcIP(3)R) mRNA inhibit the parasite host cell infection. In the present study, we identified the spliced leader (SL) acceptor of pre TcIP(3)R mRNA and synthesized MAO, which inhibited trans-splicing of the transcript (MAO-1). MAO-1 was found to inhibit the addition of SL-RNA to pre TcIP(3)R mRNA by real-time RT-PCR analysis. Treatment of the parasites with MAO-1 significantly impaired the growth and infectivity into host cells. These results indicate that MAO-1 is a potential novel drug for Chagas disease and that MAOs inhibiting trans-splicing can be used to investigate the physiology of trypanosomal genes leading to the development of novel drugs. PMID- 26680161 TI - Doctor is struck off for racist remarks and poor clinical performance. PMID- 26680160 TI - Novel methods for the molecular discrimination of Fasciola spp. on the basis of nuclear protein-coding genes. AB - Fasciolosis is an economically important disease of livestock caused by Fasciola hepatica, Fasciola gigantica, and aspermic Fasciola flukes. The aspermic Fasciola flukes have been discriminated morphologically from the two other species by the absence of sperm in their seminal vesicles. To date, the molecular discrimination of F. hepatica and F. gigantica has relied on the nucleotide sequences of the internal transcribed spacer 1 (ITS1) region. However, ITS1 genotypes of aspermic Fasciola flukes cannot be clearly differentiated from those of F. hepatica and F. gigantica. Therefore, more precise and robust methods are required to discriminate Fasciola spp. In this study, we developed PCR restriction fragment length polymorphism and multiplex PCR methods to discriminate F. hepatica, F. gigantica, and aspermic Fasciola flukes on the basis of the nuclear protein coding genes, phosphoenolpyruvate carboxykinase and DNA polymerase delta, which are single locus genes in most eukaryotes. All aspermic Fasciola flukes used in this study had mixed fragment pattern of F. hepatica and F. gigantica for both of these genes, suggesting that the flukes are descended through hybridization between the two species. These molecular methods will facilitate the identification of F. hepatica, F. gigantica, and aspermic Fasciola flukes, and will also prove useful in etiological studies of fasciolosis. PMID- 26680162 TI - Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost effectiveness modelling. AB - BACKGROUND: Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation. OBJECTIVE: To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. DATA SOURCES: We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke's Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. METHODS: In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year. RESULTS: A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I(2) = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention. LIMITATION: Heterogeneity in meta-analyses. CONCLUSIONS: While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003727. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26680165 TI - CLIMATE. Earth's lakes are warming faster than its air. PMID- 26680163 TI - Breakthrough to genome editing. PMID- 26680166 TI - CLIMATE. Carbon trackers could help bolster climate vows. PMID- 26680167 TI - CLIMATE. Inside the Paris climate deal. PMID- 26680168 TI - PALEOECOLOGY. Human impacts on ecosystems began thousands of years ago. PMID- 26680169 TI - INFECTIOUS DISEASE. Camel vaccine offers hope to stop MERS. PMID- 26680170 TI - ECOLOGY. NSF looks for new contractor to finish troubled observatory. PMID- 26680171 TI - INFECTIOUS DISEASE. Campaign against TB steps up its ambitions. PMID- 26680172 TI - Making the cut. PMID- 26680173 TI - Runners-up. PMID- 26680174 TI - Scorecard for 2015. PMID- 26680175 TI - Areas to watch in 2016. PMID- 26680176 TI - Breakdown of the year: Assault on the past. PMID- 26680177 TI - ECOLOGY. Adrift in an ocean of change. PMID- 26680178 TI - MATERIALS SCIENCE. Disclosing boron's thinnest side. PMID- 26680179 TI - QUANTUM SIMULATION. Josephson contacts of neutral strongly interacting fermions. PMID- 26680180 TI - SCIENCE GOVERNANCE. A more systematic approach to biological risk. PMID- 26680181 TI - CONSERVATION POLICY. Questionable policy for large carnivore hunting. PMID- 26680182 TI - MICROBIOLOGY. Sulfate to go. PMID- 26680183 TI - NEUROSCIENCE. Opting in or out of the network. PMID- 26680184 TI - SYNTHETIC BIOLOGY. Designer cells finely tuned for therapy. PMID- 26680185 TI - Retraction. Observation of chiral currents at the magnetic domain boundary of a topological insulator. PMID- 26680186 TI - Preventing tropical mining disasters. PMID- 26680187 TI - The global warming hiatus's irrelevance. PMID- 26680188 TI - Comment on "Dilution limits dissolved organic carbon utilization in the deep ocean". AB - Arrieta et al. (Reports, 17 April 2015, p. 331) propose that low concentrations of labile dissolved organic carbon (DOC) preclude prokaryotic consumption of a substantial fraction of DOC in the deep ocean and that this dilution acts as an alternative mechanism to recalcitrance for long-term DOC storage. Here, we show that the authors' data do not support their claims. PMID- 26680189 TI - Response to Comment on "Dilution limits dissolved organic carbon utilization in the deep ocean". AB - Our recent finding that dilution limits dissolved organic carbon (DOC) utilization in the deep ocean has been criticized based on the common misconception that lability equates to rapid and complete utilization. Even when considering the redefinition of recalcitrant DOC recently proposed by Jiao et al., the dilution hypothesis best explains our experimental observations. PMID- 26680191 TI - Connecting strongly correlated superfluids by a quantum point contact. AB - Point contacts provide simple connections between macroscopic particle reservoirs. In electric circuits, strong links between metals, semiconductors, or superconductors have applications for fundamental condensed-matter physics as well as quantum information processing. However, for complex, strongly correlated materials, links have been largely restricted to weak tunnel junctions. We studied resonantly interacting Fermi gases connected by a tunable, ballistic quantum point contact, finding a nonlinear current-bias relation. At low temperature, our observations agree quantitatively with a theoretical model in which the current originates from multiple Andreev reflections. In a wide contact geometry, the competition between superfluidity and thermally activated transport leads to a conductance minimum. Our system offers a controllable platform for the study of mesoscopic devices based on strongly interacting matter. PMID- 26680190 TI - Genomic islands of speciation separate cichlid ecomorphs in an East African crater lake. AB - The genomic causes and effects of divergent ecological selection during speciation are still poorly understood. Here we report the discovery and detailed characterization of early-stage adaptive divergence of two cichlid fish ecomorphs in a small (700 meters in diameter) isolated crater lake in Tanzania. The ecomorphs differ in depth preference, male breeding color, body shape, diet, and trophic morphology. With whole-genome sequences of 146 fish, we identified 98 clearly demarcated genomic "islands" of high differentiation and demonstrated the association of genotypes across these islands with divergent mate preferences. The islands contain candidate adaptive genes enriched for functions in sensory perception (including rhodopsin and other twilight-vision-associated genes), hormone signaling, and morphogenesis. Our study suggests mechanisms and genomic regions that may play a role in the closely related mega-radiation of Lake Malawi. PMID- 26680192 TI - Direct observation of collective modes coupled to molecular orbital-driven charge transfer. AB - Correlated electron systems can undergo ultrafast photoinduced phase transitions involving concerted transformations of electronic and lattice structure. Understanding these phenomena requires identifying the key structural modes that couple to the electronic states. We report the ultrafast photoresponse of the molecular crystal Me4P[Pt(dmit)2]2, which exhibits a photoinduced charge transfer similar to transitions between thermally accessible states, and demonstrate how femtosecond electron diffraction can be applied to directly observe the associated molecular motions. Even for such a complex system, the key large amplitude modes can be identified by eye and involve a dimer expansion and a librational mode. The dynamics are consistent with the time-resolved optical study, revealing how the electronic, molecular, and lattice structures together facilitate ultrafast switching of the state. PMID- 26680193 TI - Josephson effect in fermionic superfluids across the BEC-BCS crossover. AB - The Josephson effect is a macroscopic quantum phenomenon that reveals the broken symmetry associated with any superfluid state. Here we report on the observation of the Josephson effect between two fermionic superfluids coupled through a thin tunneling barrier. We show that the relative population and phase are canonically conjugate dynamical variables throughout the crossover from the molecular Bose Einstein condensate (BEC) to the Bardeen-Cooper-Schrieffer (BCS) superfluid regime. For larger initial excitations from equilibrium, the dynamics of the superfluids become dissipative, which we ascribe to the propagation of vortices through the superfluid bulk. Our results highlight the robust nature of resonant superfluids. PMID- 26680194 TI - Nitrogen-doped mesoporous carbon of extraordinary capacitance for electrochemical energy storage. AB - Carbon-based supercapacitors can provide high electrical power, but they do not have sufficient energy density to directly compete with batteries. We found that a nitrogen-doped ordered mesoporous few-layer carbon has a capacitance of 855 farads per gram in aqueous electrolytes and can be bipolarly charged or discharged at a fast, carbon-like speed. The improvement mostly stems from robust redox reactions at nitrogen-associated defects that transform inert graphene-like layered carbon into an electrochemically active substance without affecting its electric conductivity. These bipolar aqueous-electrolyte electrochemical cells offer power densities and lifetimes similar to those of carbon-based supercapacitors and can store a specific energy of 41 watt-hours per kilogram (19.5 watt-hours per liter). PMID- 26680195 TI - Synthesis of borophenes: Anisotropic, two-dimensional boron polymorphs. AB - At the atomic-cluster scale, pure boron is markedly similar to carbon, forming simple planar molecules and cage-like fullerenes. Theoretical studies predict that two-dimensional (2D) boron sheets will adopt an atomic configuration similar to that of boron atomic clusters. We synthesized atomically thin, crystalline 2D boron sheets (i.e., borophene) on silver surfaces under ultrahigh-vacuum conditions. Atomic-scale characterization, supported by theoretical calculations, revealed structures reminiscent of fused boron clusters with multiple scales of anisotropic, out-of-plane buckling. Unlike bulk boron allotropes, borophene shows metallic characteristics that are consistent with predictions of a highly anisotropic, 2D metal. PMID- 26680196 TI - Visualization of O-O peroxo-like dimers in high-capacity layered oxides for Li ion batteries. AB - Lithium-ion (Li-ion) batteries that rely on cationic redox reactions are the primary energy source for portable electronics. One pathway toward greater energy density is through the use of Li-rich layered oxides. The capacity of this class of materials (>270 milliampere hours per gram) has been shown to be nested in anionic redox reactions, which are thought to form peroxo-like species. However, the oxygen-oxygen (O-O) bonding pattern has not been observed in previous studies, nor has there been a satisfactory explanation for the irreversible changes that occur during first delithiation. By using Li2IrO3 as a model compound, we visualize the O-O dimers via transmission electron microscopy and neutron diffraction. Our findings establish the fundamental relation between the anionic redox process and the evolution of the O-O bonding in layered oxides. PMID- 26680197 TI - Rice perception of symbiotic arbuscular mycorrhizal fungi requires the karrikin receptor complex. AB - In terrestrial ecosystems, plants take up phosphate predominantly via association with arbuscular mycorrhizal fungi (AMF). We identified loss of responsiveness to AMF in the rice (Oryza sativa) mutant hebiba, reflected by the absence of physical contact and of characteristic transcriptional responses to fungal signals. Among the 26 genes deleted in hebiba, DWARF 14 LIKE is, the one responsible for loss of symbiosis . It encodes an alpha/beta-fold hydrolase, that is a component of an intracellular receptor complex involved in the detection of the smoke compound karrikin. Our finding reveals an unexpected plant recognition strategy for AMF and a previously unknown signaling link between symbiosis and plant development. PMID- 26680199 TI - A protein trisulfide couples dissimilatory sulfate reduction to energy conservation. AB - Microbial sulfate reduction has governed Earth's biogeochemical sulfur cycle for at least 2.5 billion years. However, the enzymatic mechanisms behind this pathway are incompletely understood, particularly for the reduction of sulfite-a key intermediate in the pathway. This critical reaction is performed by DsrAB, a widespread enzyme also involved in other dissimilatory sulfur metabolisms. Using in vitro assays with an archaeal DsrAB, supported with genetic experiments in a bacterial system, we show that the product of sulfite reduction by DsrAB is a protein-based trisulfide, in which a sulfite-derived sulfur is bridging two conserved cysteines of DsrC. Physiological studies also reveal that sulfate reduction rates are determined by cellular levels of DsrC. Dissimilatory sulfate reduction couples the four-electron reduction of the DsrC trisulfide to energy conservation. PMID- 26680198 TI - Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure. AB - Dysfunction of microRNA (miRNA) metabolism is thought to underlie diseases affecting motoneurons. One miRNA, miR-218, is abundantly and selectively expressed by developing and mature motoneurons. Here we show that mutant mice lacking miR-218 die neonatally and exhibit neuromuscular junction defects, motoneuron hyperexcitability, and progressive motoneuron cell loss, all of which are hallmarks of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Gene profiling reveals that miR-218 modestly represses a cohort of hundreds of genes that are neuronally enriched but are not specific to a single neuron subpopulation. Thus, the set of messenger RNAs targeted by miR 218, designated TARGET(218), defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration. PMID- 26680201 TI - Beetle horns and book writing. PMID- 26680200 TI - An essential cell cycle regulation gene causes hybrid inviability in Drosophila. AB - Speciation, the process by which new biological species arise, involves the evolution of reproductive barriers, such as hybrid sterility or inviability between populations. However, identifying hybrid incompatibility genes remains a key obstacle in understanding the molecular basis of reproductive isolation. We devised a genomic screen, which identified a cell cycle-regulation gene as the cause of male inviability in hybrids resulting from a cross between Drosophila melanogaster and D. simulans. Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae. Our genomic method provides a facile means to accelerate the identification of hybrid incompatibility genes in other model and nonmodel systems. PMID- 26680202 TI - Structure of the voltage-gated calcium channel Cav1.1 complex. AB - The voltage-gated calcium channel Ca(v)1.1 is engaged in the excitation contraction coupling of skeletal muscles. The Ca(v)1.1 complex consists of the pore-forming subunit alpha1 and auxiliary subunits alpha2delta, beta, and gamma. We report the structure of the rabbit Ca(v)1.1 complex determined by single particle cryo-electron microscopy. The four homologous repeats of the alpha1 subunit are arranged clockwise in the extracellular view. The gamma subunit, whose structure resembles claudins, interacts with the voltage-sensing domain of repeat IV (VSD(IV)), whereas the cytosolic beta subunit is located adjacent to VSD(II) of alpha1. The alpha2 subunit interacts with the extracellular loops of repeats I to III through its VWA and Cache1 domains. The structure reveals the architecture of a prototypical eukaryotic Ca(v) channel and provides a framework for understanding the function and disease mechanisms of Ca(v) and Na(v) channels. PMID- 26680204 TI - Opportunities and challenges in liquid cell electron microscopy. AB - Transmission electron microscopy offers structural and compositional information with atomic resolution, but its use is restricted to thin, solid samples. Liquid samples, particularly those involving water, have been challenging because of the need to form a thin liquid layer that is stable within the microscope vacuum. Liquid cell electron microscopy is a developing technique that allows us to apply the powerful capabilities of the electron microscope to imaging and analysis of liquid specimens. We describe its impact in materials science and biology. We discuss how its applications have expanded via improvements in equipment and experimental techniques, enabling new capabilities and stimuli for samples in liquids, and offering the potential to solve grand challenge problems. PMID- 26680203 TI - Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist. AB - Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav channels are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian Nav channel isoforms share high sequence identity and remain recalcitrant to high-resolution structural studies. Targeting the human Nav1.7 channel involved in pain perception, we present a protein-engineering strategy that has allowed us to determine crystal structures of a novel receptor site in complex with isoform-selective antagonists. GX-936 and related inhibitors bind to the activated state of voltage-sensor domain IV (VSD4), where their anionic aryl sulfonamide warhead engages the fourth arginine gating charge on the S4 helix. By opposing VSD4 deactivation, these compounds inhibit Nav1.7 through a voltage-sensor trapping mechanism, likely by stabilizing inactivated states of the channel. Residues from the S2 and S3 helices are key determinants of isoform selectivity, and bound phospholipids implicate the membrane as a modulator of channel function and pharmacology. Our results help to elucidate the molecular basis of voltage sensing and establish structural blueprints to design selective Nav channel antagonists. PMID- 26680205 TI - The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection. AB - CD8(+) T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-gamma. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8(+) T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1(-/-) mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV specific CD8(+) T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8(+) T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8(+) T cell responses during an acute poxvirus infection. PMID- 26680207 TI - Inhibition of the TNF Family Cytokine RANKL Prevents Autoimmune Inflammation in the Central Nervous System. AB - The central nervous system (CNS) is an immunologically privileged site protected from uncontrolled access of T cells by the blood-brain barrier (BBB), which is breached upon autoimmune inflammation. Here we have shown that receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) on T cells regulates C-C type chemokine ligand 20 (CCL20) production by astrocytes and T cell localization in the CNS. Importantly, mice specifically lacking RANKL in T cells were resistant to experimental autoimmune encephalomyelitis (EAE) due to altered T cell trafficking. Pharmacological inhibition of RANKL prevented the development of EAE without affecting the peripheral immune response, indicating that RANKL is a potential therapeutic target for treating autoimmune diseases in the CNS. PMID- 26680206 TI - Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. AB - Atherosclerosis is a chronic inflammatory disease of arterial wall. Mitochondrial DNA (mtDNA) and human antimicrobial peptide LL-37 (Cramp in mice) are involved in atherosclerosis. Recently, mtDNA has been found to escape from autophagy and cause inflammation. Normally, mtDNA as an inflammatogenic factor cannot escape from autophagy and degradation by DNase II. In this study, we found elevated amounts of LL37-mtDNA complex in atherosclerotic plasma and plaques. The complex was resistant to DNase II degradation and escaped from autophagic recognition, leading to activation of Toll-like receptor 9 (TLR9)-mediated inflammatory responses. Mouse model studies indicated that Cramp-mtDNA complex aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice and antibody treatment against the complex alleviated the lesion. These findings suggest that the LL-37-mtDNA complex acts as a key mediator of atherosclerosis formation, and thus represents a promising therapeutic target. PMID- 26680208 TI - A Spatially Continuous Model of Carbohydrate Digestion and Transport Processes in the Colon. AB - A spatially continuous mathematical model of transport processes, anaerobic digestion and microbial complexity as would be expected in the human colon is presented. The model is a system of first-order partial differential equations with context determined number of dependent variables, and stiff, non-linear source terms. Numerical simulation of the model is used to elucidate information about the colon-microbiota complex. It is found that the composition of materials on outflow of the model does not well-describe the composition of material in other model locations, and inferences using outflow data varies according to model reactor representation. Additionally, increased microbial complexity allows the total microbial community to withstand major system perturbations in diet and community structure. However, distribution of strains and functional groups within the microbial community can be modified depending on perturbation length and microbial kinetic parameters. Preliminary model extensions and potential investigative opportunities using the computational model are discussed. PMID- 26680209 TI - Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors. AB - Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart. PMID- 26680210 TI - The Prospective Links Between Hyperactive/Impulsive, Inattentive, and Oppositional-Defiant Behaviors in Childhood and Antisocial Behavior in Adolescence: The Moderating Influence of Gender and the Parent-Child Relationship Quality. AB - We prospectively investigated the effect of child hyperactive/impulsive, inattentive, and oppositional/defiant behaviors on the development of youth antisocial behaviors, and the moderating influence of gender and the parent-child relationship quality in a normative sample. Participants (N = 673, 50 % girls) were assessed at 10 years of age (parent reports) and at age 15 (parent and adolescent reports). Using latent change models, we found that initial levels of, as well as increases in, hyperactivity/impulsivity and oppositional behaviors and initial levels of inattention behaviors predicted youth antisocial behaviors. The increase in oppositional behaviors was predictive of youth antisocial behaviors in girls only. Child hyperactive/impulsive behaviors predicted youth antisocial behaviors only in children for whom the quality of the parent-child relationship deteriorated from childhood to adolescence. Thus, both initial levels of and increases in disruptive behaviors as well as gender are important for understanding the development of antisocial behaviors in adolescence. We received partial support for the hypothesized, moderating role of a high-quality parent child relationship. PMID- 26680211 TI - The Trade-Off between Female Fertility and Longevity during the Epidemiological Transition in the Netherlands. AB - Several hypotheses have been put forward to explain the relationship between women's fertility and their post-reproductive longevity. In this study, we focus on the disposable soma theory, which posits that a negative relationship between women's fertility and longevity can be understood as an evolutionary trade-off between reproduction and survival. We examine the relationship between fertility and longevity during the epidemiological transition in the Netherlands. This period of rapid decline in mortality from infectious diseases offers a good opportunity to study the relationship between fertility and longevity, using registry data from 6,359 women born in The Netherlands between 1850 and 1910. We hypothesize that an initially negative relationship between women's fertility and their longevity gradually turns less negative during the epidemiological transition, because of decreasing costs of higher parities. An initially inversed U-shaped association between fertility and longevity changes to zero during the epidemiological transition. This does suggest a diminishing environmental pressure on fertility. However, we find no evidence of an initial linear trade off between fertility and post-reproductive survival. PMID- 26680212 TI - 3D Tissue Formation of Unilocular Adipocytes in Hydrogel Microfibers. AB - Adipose tissue, an active metabolic and endocrine organ mainly composed of unilocular adipocytes, is implicated in various obesity related diseases. Developing morphologically and functionally accurate in vitro models of the adipose tissue is therefore critically important for basic biological studies, drug screening/testing, and clinical implants to advance the understanding and treatment of these diseases. However, current adipose tissue engineering technologies either cannot replicate the unilocular morphologies of mature adipocytes, or lack the ease of monitoring, handling, and scaling up required in the above mentioned applications. This paper presents the differentiation of adipose derived stem cells (ADSCs) to mature adipocytes in highly observable and highly handleable 3D fiber shaped constructs exhibiting morphologies and functions of native adipose tissues. Using the cell fiber technology, ADSCs were encapsulated in hydrogel microfibers, allowed to form into fiber shaped constructs, and differentiated to mature unilocular adipocytes. These adipocyte fibers are observed and maintained for up to 91 d, and secretion of adipose tissue-specific factor, adiponectin, is further confirmed. The handleability of the adipocyte fibers is demonstrated by assembling the adipocyte fibers into doll shaped constructs. Such highly observable, highly handleable, and scalable characteristics of the adipocyte fibers make them suitable for biological studies, high-throughput drug screening/testing, and clinical applications. PMID- 26680213 TI - Applicability of next generation balloon-expandable transcatheter heart valves in aortic annuli exceeding formally approved dimensions. AB - OBJECTIVES: Physicians are frequently confronted with patients suffering from aortic stenosis with annular diameters exceeding dimensions in which currently available transcatheter heart valves (THV) are formally approved. Experience in patients receiving significantly undersized Sapien 3 (S3) THV (Edwards Lifesciences, Inc., Irvine, CA, USA) in aortic annuli up to 32 mm has not been reported so far. METHODS: Patients with aortic annuli exceeding the formally determined upper size limit and who received a 29 mm S3, were identified from our database. Calcification pattern and annulus dimension were analyzed retrospectively using the 3mensio Medical Imaging software. Clinical endpoints were adjudicated in accordance with the updated standardized VARC-2 definitions. RESULTS: 21 consecutive patients with aortic annuli >=28.1 mm received a 29 mm THV. All patients were male (77.4 +/- 8.1 year, logEuroSCORE I 22.5 +/- 14.1 %). Multi-slice computed tomography and transesophageal echocardiography derived annular dimensions were 30.2 +/- 1.5 vs. 28.8 +/- 0.9 mm (p = 0.0001). Total calcium load of the aortic valves was 1327 +/- 957 mm(3). Device success according to VARC-2 definitions was achieved in 100 % (21/21). All-cause 30-day mortality was 0 % (0/21). Rate of permanent pacemaker implantation was 14.3 % (3/21). No paravalvular leakage >= grade II was detectable. CONCLUSIONS: Preliminary experience suggests implantation of this type of THV in aortic annuli up to 32 mm to be feasible and safe, in particular calcification patterns. It does not result in a relevant incidence of PVL >= grade II, or increased rate of VARC-2 adjudicated clinical endpoints. Also, functional outcomes regarding transvalvular gradients or EOA demonstrate applicability of this THV in such patients. PMID- 26680215 TI - What can we expect of health in old age? PMID- 26680214 TI - Epidemiology of non-fatal injuries among Egyptian children: a community-based cross-sectional survey. AB - BACKGROUND: Injuries are a major cause of childhood morbidity and mortality worldwide. We aimed to determine the magnitude and characteristics of child injuries in Egypt and to identify the associated risk factors. METHODS: A community-based, cross-sectional survey was conducted over 27 Egyptian governorates from June to October, 2011. The target population was 1977 households with children aged 0-18 years who had experienced accidental injuries. RESULTS: In the 6-month period before the investigation, 1576 injuries were reported in 1472 children from a sample population of 1399 households (response rate 70.8 %). Falls (25 %) and burn injuries (20.3 %) were the most common accidental injuries. The incidence of these injuries was significantly higher among boys (57.2 %) than girls and in children aged 2-6 years (70 %) compared with older and younger children. The five main causes of injuries were wounds (30.6 %), fractures (28.7 %), burns (20.3 %), swallowing a foreign body (8.4 %) and accidentally ingesting a poison (7.8 %). Injuries from drowning (n = 27), animal bites (n = 22) and sunstroke (n = 20) mostly occurred in rural children, accounting for 65 %, 54.4 % and 52 %, respectively, of all injuries in rural children. Home and its immediate surroundings (64.4 %) was the most common setting for injuries. Maternal age, education and working status were also associated with childhood injuries (p < 0.05). Children of second and third birth order were at higher risk for injuries (p < 0.0001). CONCLUSIONS: Childhood injuries account for a substantial healthcare burden in Egypt. Our findings emphasise the importance of developing national preventive programs designed to reduce the incidence of childhood injuries. PMID- 26680216 TI - Equal access to colorectal cancer screening. PMID- 26680217 TI - Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster randomised controlled trials. AB - BACKGROUND: Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. METHODS: All people eligible for screening (men and women aged 60-74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July-August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. FINDINGS: As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0.5%). Trials 1 (n=163,525) and 2 (n=150,417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1.07, 95% CI 1.04-1.10, p<0.0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0.005), with a stronger effect in the most deprived quintile (adjusted OR 1.11, 95% CI 1.04 1.20, p=0.003) than in the least deprived (1.00, 0.94-1.06, p=0.98). Overall uptake was also increased (1.07, 1.03-1.11, p=0.001). INTERPRETATION: Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging. FUNDING: National Institute for Health Research. PMID- 26680218 TI - A comparison of health expectancies over two decades in England: results of the Cognitive Function and Ageing Study I and II. AB - BACKGROUND: Whether rises in life expectancy are increases in good-quality years is of profound importance worldwide, with population ageing. We investigate how various health expectancies have changed in England between 1991 and 2011, with identical study design and methods in each decade. METHODS: Baseline data from the Cognitive Function and Ageing Studies in populations aged 65 years or older in three geographically defined centres in England (Cambridgeshire, Newcastle, and Nottingham) provided prevalence estimates for three health measures: self perceived health (defined as excellent-good, fair, or poor); cognitive impairment (defined as moderate-severe, mild, or none, as assessed by Mini-Mental State Examination score); and disability in activities of daily living (defined as none, mild, or moderate-severe). Health expectancies for the three regions combined were calculated by the Sullivan method, which applies the age-specific and sex-specific prevalence of the health measure to a standard life table for the same period. FINDINGS: Between 1991 and 2011, gains in life expectancy at age 65 years (4.5 years for men and 3.6 years for women) were accompanied by equivalent gains in years free of any cognitive impairment (4.2 years [95% CI 4.2 4.3] for men and 4.4 years [4.3-4.5] for women) and decreased years with mild or moderate-severe cognitive impairment. Gains were also identified in years in excellent or good self-perceived health (3.8 years [95% CI 3.5-4.1] for men and 3.1 years [2.7-3.4] for women). Gains in disability-free years were much smaller than those in excellent-good self-perceived health or those free from cognitive impairment, especially for women (0.5 years [0.2-0.9] compared with 2.6 years [2.3-2.9] for men), mostly because of increased mild disability. INTERPRETATION: During the past two decades in England, we report an absolute compression (ie, reduction) of cognitive impairment, a relative compression of self-perceived health (ie, proportion of life spent healthy is increasing), and dynamic equilibrium of disability (ie, less severe disability is increasing but more severe disability is not). Reasons for these patterns are unknown but might include increasing obesity during previous decades. Our findings have wide ranging implications for health services and for extension of working life. FUNDING: UK Medical Research Council. PMID- 26680220 TI - Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion. AB - Paternally expressed gene 10 (PEG10) is an imprinted and monoallelic expressed gene. Previous study using a knockout mouse model revealed a crucial role of PEG10 in placental development, yet the exact function of PEG10 during placentation remains to be elucidated. In this study, denuded chorionic villi were prepared from first trimester human placentas, and transduced with PEG10 small interference RNA (siRNA) or non-targeting control sequence by lentiviral infection. Immunohistochemical staining revealed that silencing of PEG10 in the chorionic villous explants resulted in reduced immune-reactivity to CK7, Ki67 and integrin alpha5, implying that silencing of PEG10 impaired the proliferation of villous trophoblasts and may interfere with the activity of extravillous trophoblasts. We further investigated the role of PEG10 in the proliferation, migration and invasion of JEG-3 trophoblast cell line and the primary chorionic villous cells. PEG10-silenced JEG-3 cells and primary chorionic villous cells displayed a reduced proliferation rate and impaired invasiveness in vitro. Silencing of PEG10 in trophoblast cells led to upregulated expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as downregulated expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, knockdown of TIMP-1 reversed the suppressed invasiveness of PEG10 siRNA-transduced JEG-3 cells. In conclusion, our study demonstrates that PEG10 plays an important role in trophoblast proliferation and promotes trophoblast invasion through TIMP-1. PMID- 26680219 TI - Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women. AB - Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process. PMID- 26680222 TI - Small Bowel Gastrointestinal Stromal Tumor (GIST) Presenting with Liver Abscesses. PMID- 26680221 TI - Antifungal effect and action mechanism of antimicrobial peptide polybia-CP. AB - The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. PMID- 26680223 TI - The complete mitochondrial genome of the altum angelfish Pterophyllum altum (Pellegrin, 1903). AB - In this study, the complete mitogenome sequence of the altum angelfish Pterophyllum altum (Pellegrin, 1903) has been sequenced by next-generation sequencing method. The mitogenome consists of 16 495 bp, including 13 protein coding genes, 22 transfer RNAs and 2 ribosomal RNAs genes. The overall base composition of P. altum is 27.5% for A, 30.3% for C, 15.5% for G, and 26.7% for T, which shows a 92% identity to P. scalare. The complete mitogenome of the P. altum provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for the genus Pterophyllum phylogeny. PMID- 26680224 TI - Propelling Immunotherapy Combinations Into the Clinic. AB - Immune checkpoint inhibitors produce durable long-term survival in some patients with advanced melanoma and lung cancer. Better immune targets and combination strategies can harness the immune system by supporting the three elements of a successful T-cell antitumor response: (A) generation of sufficient numbers of antitumor T cells within the lymphoid compartment; (B) effective T-cell trafficking and extravasation out of the lymphoid compartment, through the bloodstream, and into the tumor microenvironment; and (C) T-cell effector function within the tumor microenvironment that is characterized by the ability to bypass immune checkpoints, soluble and metabolic inhibitory factors, and inhibitory cells. Strategies that hold promise include dual immune checkpoint blockade, as well as the combination of immune checkpoint blockade with costimulatory receptor agonists, enhancers of innate immunity, inhibition of indoleamine 2,3-dioxygenase, adoptive T-cell transfer/T-cell engineering, therapeutic vaccines, small-molecule inhibitors, and radiation therapy. Novel, rational clinical trial designs seek to combine targeted agents and one or more immune checkpoint inhibitors, with the goal of producing deep and durable antitumor responses, which thus far have been observed in only a minority of patients. PMID- 26680225 TI - Combination Immunotherapy: An Emerging Paradigm in Cancer Therapeutics. PMID- 26680226 TI - Identification of a novel antimicrobial peptide from amphioxus Branchiostoma japonicum by in silico and functional analyses. AB - The emergence of multi-drug resistant (MDR) microbes leads to urgent demands for novel antibiotics exploration. We demonstrated a cDNA from amphioxus Branchiostoma japonicum, designated Bjamp1, encoded a protein with features typical of antimicrobial peptides (AMPs), which is not homologous to any AMPs currently discovered. It was found that Bjamp1 was expressed in distinct tissues, and its expression was remarkably up-regulated following challenge with LPS and LTA. Moreover, the synthesized putative mature AMP, mBjAMP1, underwent a coil-to helix transition in the presence of TFE or SDS, agreeing well with the expectation that BjAMP1 was a potential AMP. Functional assays showed that mBjAMP1 inhibited the growth of all the bacteria tested, and induced membrane/cytoplasmic damage. ELISA indicated that mBjAMP1 was a pattern recognition molecule capable of identifying LPS and LTA. Importantly, mBjAMP1 disrupted the bacterial membranes by a membranolytic mechanism. Additionally, mBjAMP1 was non-cytotoxic to mammalian cells. Collectively, these data indicate that mBjAMP1 is a new AMP with a high bacterial membrane selectivity, rendering it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows for the first time that use of signal conserved sequence of AMPs is effective identifying potential AMPs across different animal classes. PMID- 26680229 TI - Recent development of biomedical research at the Institute of Physiology of the Czech Academy of Sciences in Prague. PMID- 26680227 TI - XBP1 silencing decreases glioma cell viability and glycolysis possibly by inhibiting HK2 expression. AB - Glioma cells rely on glycolysis to obtain energy and sustain their survival under microenvironmental stress in vivo. The mechanisms of regulation of glycolysis in glioma cells are unclear. Signaling pathway mediated by the transcription factor X box-binding protein 1 (XBP1) is one of the most important pathways of unfolded protein response which is comprehensively activated in cancer cells upon the microenvironmental stress. Here we showed that XBP1 was significantly activated in glioma tissues in vivo. XBP1 silencing resulted in decreasing of glioma cell viability and ATP/lactate production under hypoxia, which is possibly mediated by inhibition of Hexokinase II (HK2)'s expression. More importantly, XBP1 silenced glioma cells showed the decrease of tumor formation capacity. Our results revealed that XBP1s activation was involved in glioma glycolysis regulation and might be a potential molecular target for glioma treatment. PMID- 26680230 TI - Epigenetics and a new look on metabolic syndrome. AB - The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental factors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factors but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics. PMID- 26680228 TI - Characterisation of Arabidopsis calnexin 1 and calnexin 2 in the endoplasmic reticulum and at plasmodesmata. AB - Calnexin (CNX) is a highly conserved endoplasmic reticulum (ER) chaperone protein. Both calnexin and the homologous ER-lumenal protein, calreticulin, bind calcium ions and participate in protein folding. There are two calnexins in Arabidopsis thaliana, CNX1 and CNX2. GUS expression demonstrated that these are expressed in most Arabidopsis tissues throughout development. Calnexin transfer DNA (T-DNA) mutant lines exhibited increased transcript abundances of a number of other ER chaperones, including calreticulins, suggesting a degree of redundancy. CNX1 and CNX2 localised to the ER membrane including that within plasmodesmata, the intercellular channels connecting plant cells. This is comparable with the previous localisations of calreticulin in the ER lumen and at plasmodesmata. However, from green fluorescent protein (GFP) diffusion studies in single and double T-DNA insertion mutant lines, as well as overexpression lines, we found no evidence that CNX1 or CNX2 play a role in intercellular transport through plasmodesmata. In addition, calnexin T-DNA mutant lines showed no change in transcript abundance of a number of plasmodesmata-related proteins. CNX1 and CNX2 do not appear to have a specific localisation or function at plasmodesmata-rather the association of calnexin with the ER is simply maintained as the ER passes through plasmodesmata. PMID- 26680232 TI - Natural Hg isotopic composition of different Hg compounds in mammal tissues as a proxy for in vivo breakdown of toxic methylmercury. AB - In the last decade, specific attention has been paid to total mercury (HgT) stable isotopic composition, especially in natural samples such as aquatic organisms, due to its potential to track the cycle of this toxic element in the environment. Here, we investigated Hg Compound Specific stable Isotopic Composition (CSIC) of natural inorganic Hg (iHg) and methylmercury (MMHg) in various tissues of aquatic mammals (Beluga whale from the Arctic marine environment and seals from the freshwater lake Baikal, Russia). In seals' organs the variation in mass dependent fractionation (MDF, delta(202)Hg) for total Hg was significantly correlated to the respective fraction of iHg and MMHg compounds, with MMHg being enriched by ~ 30/00 in heavier isotopes relative to iHg. On the other hand, we observe insignificant variation in Hg mass independent isotope fractionation (MIF, Delta(199)Hg) among iHg and MMHg in all organs for the same mammal species and MMHg in prey items. MIF signatures suggest that both MMHg and iHg in aquatic mammals have the same origin (i.e., MMHg from food), and are representative of Hg photochemistry in the water column of the mammal ecosystem. MDF signatures of Hg compounds indicate that MMHg is demethylated in vivo before being stored in the muscle, and the iHg formed is stored in the liver, and to a lesser extent in the kidney, before excretion. Thus, Hg CSIC analysis in mammals can be a powerful tool for tracing the metabolic response to Hg exposure. PMID- 26680231 TI - Consistent gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma. AB - BACKGROUND: The MexTAg transgenic mouse model of mesothelioma replicates many aspects of human mesothelioma, including induction by asbestos, pathogenicity and response to cytotoxic chemotherapy, despite high levels of the SV40 large T Antigen (TAg) in the mesothelial compartment. This model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out. METHODS: Gene expression of MexTAg mesothelioma cell lines bearing a high or low number of copies of the TAg transgene were compared to wild type mouse mesotheliomas and normal mouse mesothelial cells using Affymetrix microarray. These data were then compared to a similar published human microarray study using the same platform. RESULTS: The main expression differences between transgenic mouse and wild type mouse mesotheliomas occurred for genes involved in cell cycle regulation and DNA replication, as would be expected from overexpression of the TAg oncogene. Quantitative PCR confirmed that E2F and E2F regulated genes were significantly more upregulated in MexTAg mesotheliomas and MexTAg mesothelial cells compared to wild type mesotheliomas. Like human mesothelioma, both MexTAg and wild type mesotheliomas had more genes underexpressed than overexpressed compared to normal mouse mesothelial cells. Most notably, the cdkn2 locus was deleted in the wild type mouse mesotheliomas, consistent with 80 % human mesotheliomas, however, this region was not deleted in MexTAg mesotheliomas. Regardless of the presence of TAg, all mouse mesotheliomas had a highly concordant set of deregulated genes compared to normal mesothelial cells that overlapped with the deregulated genes between human mesotheliomas and mesothelial cells. CONCLUSIONS: This investigation demonstrates that the MexTAg mesotheliomas are comparable with wild type mouse mesotheliomas in their representation of human mesothelioma at the molecular level, with some key gene expression differences that are attributable to the TAg transgene expression. Of particular note, MexTAg mesothelioma development was not dependent on cdkn2 deletion. PMID- 26680233 TI - Risk factors affecting human traumatic tympanic membrane perforation regeneration therapy using fibroblast growth factor-2. AB - OBJECTIVE: The use of growth factors to achieve closure of human traumatic tympanic membrane perforations (TMPs) has recently been demonstrated. However, pretreatment factors affecting healing outcomes have seldom been discussed. The objective of this study was to evaluate pretreatment factors contributing to the success or failure of healing of TMPs using fibroblast growth factor-2 (FGF-2). DESIGN AND PARTICIPANTS: A retrospective cohort study of 99 patients (43 males, 56 females) with traumatic TMPs who were observed for at least 6 months after FGF 2 treatment between March 2011 and December 2012. Eleven factors considered likely to affect the outcome of perforation closure were evaluated statistically using univariate and multivariate logistic regression analysis. INTERVENTIONS: Each traumatic TMP was treated by direct application of FGF-2. MAIN OUTCOME MEASURES: Complete closure versus failure to close. RESULTS: In total, 99 patients were analyzed. The total closure rate was 92/99 (92.9%) at 6 months; the mean closure time was 10.59 +/- 6.81 days. The closure rate did not significantly differ between perforations with or without inverted edges (100.0% vs. 91.4%, p = 0.087), among different size groups (p = 0.768), or among different periods of exposure to injury (p = 0.051). However, the closure rate was significantly different between the high- and low-dose FGF-2 groups (85.0% vs. 98.3%, p = 0.010) and between perforations where the umbo or malleus was or was not involved in perforation (85.4% vs. 98.3%, p = 0.012). Additionally, univariate logistic regression analysis tests showed that it was difficult to achieve healing of these perforations with a history of chronic otitis media or residual TM calcification (p = 0.006), the umbo or malleus was involved in perforation (p = 0.038), and with a high dose of FGF-2 (p = 0.035) compared with control groups. Multivariate logistic regression analysis showed that only a history of chronic otitis media and residual TM calcification and perforation close to the umbo or malleus were associated with non-healing of the TM perforation (p = 0.03 and p = 0.017, respectively) with relative risk factors. CONCLUSIONS: Direct application of FGF-2 can be used in all traumatic TMPs, the size of the perforation and inverted edges did not affect the closure rate, and the most beneficial dose was sufficient to keep the residual eardrum environment moist, but without adding liquid. Additionally, multivariate logistic regression analysis revealed that a large perforation was not a major risk factor for nonhealing of TM perforations. However, a history of chronic otitis media, residual TM calcification and involvement of the umbo or malleus in perforation were significant risk factors. PMID- 26680235 TI - Assembly of SnSe Nanoparticles Confined in Graphene for Enhanced Sodium-Ion Storage Performance. AB - Sodium-ion batteries (SIBs) have attracted much interest as a low-cost and environmentally benign energy storage system, but more attention is justifiably required to address the major technical issues relating to the anode materials to deliver high reversible capacity, superior rate capability, and stable cyclability. A SnSe/reduced graphene oxide (RGO) nanocomposite has been prepared by a facile ball-milling method, and its structural, morphological, and electrochemical properties have been characterized and compared with those of the bare SnSe material. Although the redox behavior of SnSe remains nearly unchanged upon the incorporation of RGO, its electrochemical performance is significantly enhanced, as reflected by a high specific capacity of 590 mA h g(-1) at 0.050 A g(-1) , a rate capability of 260 mA h g(-1) at 10 A g(-1) , and long-term stability over 120 cycles. This improvement may be attributed to the high electronic conductivity of RGO, which also serves as a matrix to buffer changes in volume and maintain the mechanical integrity of the electrode during (de)sodiation processes. In view of its excellent Na(+) storage performance, this SnSe/RGO nanocomposite has potential as an anode material for SIBs. PMID- 26680234 TI - Time-resolved amino acid uptake of Clostridium difficile 630Deltaerm and concomitant fermentation product and toxin formation. AB - BACKGROUND: Clostridium difficile is one of the major nosocomial threats causing severe gastrointestinal infections. Compared to the well documented clinical symptoms, little is known about the processes in the bacterial cell like the regulation and activity of metabolic pathways. In this study, we present time resolved and global data of extracellular substrates and products. In a second part, we focus on the correlation of fermentation products and substrate uptake with toxin production. RESULTS: Formation of different fermentation products during growth in a comparison between the two different media in a global approach was studied using non-targeted gas chromatography-mass spectrometry (GC MS) based analysis. During cultivation in a casamino acids medium and minimal medium, the clinical isolate C. difficile 630Deltaerm showed major differences in amino acid utilization: In casamino acids medium, C. difficile preferred proline, leucine and cysteine as carbon and energy sources while glutamate and lysine were not or hardly used. In contrast, proline and leucine were consumed at a significantly later stage in minimal medium. Due to the more complex substrate mixture more fermentation products were detectable in the casamino acids medium, accompanied by major changes in the ratios between oxidative and reductive Stickland products. Different glucose consumption dynamics were observed in presence of either casamino acids or the minimal set of amino acids, accompanied by major changes in butanoate formation. This was associated with a variation in both the toxin yield and a change in the ratio of toxin A to toxin B. CONCLUSIONS: Since in all media compositions, more than one substrate was available as a suitable carbon source, availability of different carbon sources and their metabolic fate appears to be the key factor for toxin formation. PMID- 26680236 TI - Complete mitochondrial genome of Toxabramis swinhonis (Cypriniformes, Cyprinidae). AB - Toxabramis swinhonis is a one of the main bycatch species in China's freshwater fishery and an important food resource for the larger fishes in the main rivers and lakes in China. For better understanding the biology of this species, the complete mitochondrial genome of Toxabramis swinhonis was determined and analyzed in this study. The complete mitogenome of T. swinhonis is 16 622 bp in length, which contains 22 transfer RNAs, 2 ribosomal RNAs, 13 protein-coding genes and 2 non-coding regions: origin of light-strand replication (OL) and control region (D loop). The determination of T. swinhonis mitogenome would play an important role in genetic diversity and evolution for Cyprinidae. PMID- 26680237 TI - The mortality of acutely ill medical patients for up to 60days after admission to a resource poor hospital in sub-Saharan Africa compared with patients of similar illness severity admitted to a Danish Regional Teaching Hospital--an exploratory observational study. AB - BACKGROUND: The outcomes of patients with the same severity of illness in the developed and developing countries have not been compared. Illness severity can now be measured anywhere by the National Early Warning Score (NEWS). METHODS: An exploratory observational study that compared the 7, 30 and 60 days mortality of 195 Ugandan and 588 Danish acutely ill medical patients that had a NEWS >6 at the time of their admission to the hospital. The association of vital sign changes, alertness and mobility at admission on subsequent outcome was explored. RESULTS: More Kitovu (34.4%) than Danish patients (22.1%) died within 60 days of admission (OR 1.85, 95% CI 1.27-2.71, p 0.001). However, the survival of non-comatose patients admitted without severely deranged vital signs or who were able to stand without help was identical in both cohorts (Chi square 0.32, p 0.57): these patients made up 50% of all Ugandan and 60% of all Danish patients. In contrast the survival curves of patients admitted in a coma were widely divergent within a week of hospital admission and remained so for a further 60 days (Chi square 10.29, p 0.001). CONCLUSION: This small hypothesis generating observational study with huge selection and treatment bias found no survival difference at 60 days after admission to resource rich and resource poor hospitals for patients without severely deranged vital signs or who were able to stand without help. PMID- 26680238 TI - Complexity reduction of clinical samples for routine mass spectrometric analysis. AB - The precise measurement of protein abundance levels in highly complex biological samples such as plasma remains challenging. The wide range of protein concentrations impairs the detection of low-abundant species and the high number of peptide components to analyze results in interferences leading to erroneous quantitative results. The advances in MS instrumentation, with improved selectivity and sensitivity, partially address these issues, but sample preparation techniques remain the pivotal element to obtain robust routine mass spectrometric assays with a low LOD. A number of methodologies have been proposed and refined over the past two decades to reduce the range of protein concentrations and the number of peptide components. Whereas most of the methods have proven their utility for discovery studies, only a few are actually applicable to routine quantitative studies. In this account, common protein- and peptide-based fractionation methods are discussed, and illustrated with practical examples, with a focus on methods suited for clinical samples scheduled for biomarker validation assays and subsequent routine clinical mass spectrometric analyses. PMID- 26680239 TI - Risks of Death and Stroke in Patients Undergoing Hemodialysis With New-Onset Atrial Fibrillation: A Competing-Risk Analysis of a Nationwide Cohort. AB - BACKGROUND: Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia. METHODS AND RESULTS: This nationwide, population-based, propensity score-matched cohort study used data from Taiwan's National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13-1.43), all-cause death (aHR, 1.59; 95% CI, 1.52-1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71-1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17-1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76-2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45-1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA2DS2-VASc score for ischemic stroke was diminished in the competing-risk model. CONCLUSIONS: The risk of stroke was only modestly higher in patients undergoing hemodialysis with new onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death. PMID- 26680240 TI - Oral Anticoagulation in Patients with End Stage Renal Disease and Atrial Fibrillation: The Need to Evaluate Net Clinical Effect. PMID- 26680241 TI - Unplanned Inpatient and Observation Rehospitalizations After Acute Myocardial Infarction: Insights From the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study. AB - BACKGROUND: Previous studies examining early readmission after acute myocardial infarction have focused exclusively on inpatient readmissions. However, from a patient's perspective, any unplanned inpatient or observation rehospitalization after acute myocardial infarction represents a significant event; these unplanned rehospitalizations have not been well characterized. METHODS AND RESULTS: We examined all patients with acute myocardial infarction treated with percutaneous coronary intervention and discharged alive from 233 hospitals in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Our primary outcome was unplanned rehospitalizations (inpatient or observation status) within 30 days after discharge. We identified factors associated with unplanned rehospitalizations using multivariable logistic regression. Among 12 312 patients, 1326 (10.8%) had 1483 unplanned rehospitalizations within 30 days of the index event: 1028 (69.3%) were inpatient readmissions, and 455 (30.7%) were observation stays. The majority of unplanned rehospitalizations (72%) were for cardiovascular reasons. Variation in hospital rates of 30-day unplanned rehospitalization ranged from 5.4% to 20.0%, with a median of 10.7%. After multivariable modeling, the factors most strongly associated with unplanned rehospitalization were baseline quality of life and depression, followed by index hospital length of stay. CONCLUSIONS: Early unplanned rehospitalizations are common after acute myocardial infarction, and close to one third were classified as an observation stay. Predischarge and postdischarge assessments of overall, not just cardiovascular, health and strategies to optimize patient functional status may help to reduce unplanned rehospitalizations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503. PMID- 26680242 TI - Unplanned Rehospitalizations and Depression: Time for a New Approach? PMID- 26680243 TI - Re: Maurice et al: Nonclinical Factors Predict Selection of Initial Observation for Renal Cell Carcinoma (Urology 2015;86:892-900). PMID- 26680244 TI - Combined Biparametric Prostate Magnetic Resonance Imaging and Prostate-specific Antigen in the Detection of Prostate Cancer: A Validation Study in a Biopsy-naive Patient Population. AB - OBJECTIVE: To validate the use of biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) and prostate-specific antigen (PSA) or PSA density (PSAD) in a biopsy-naive cohort at risk for prostate cancer (PCa). METHODS: All patients (n = 59) underwent PSA screening and digital rectal exam prior to a B-MRI followed by MRI or transrectal ultrasound fusion-guided targeted biopsy. Previously reported composite formulas incorporating screen positive lesions (SPL) on B-MRI and PSA or PSAD were developed to maximize PCa detection. For PSA, a patient was considered screen positive if PSA level + 6 * (the number of SPL) >14. For PSAD, screening was positive if PSAD * 14 + (the number of SPL) >4.25. These schemes were employed in this new test set to validate the initial formulas. Performance assessment of these formulas was determined for all cancer detection and for tumors with Gleason >=3 + 4. RESULTS: Screen positive lesions on B-MRI had the highest sensitivity (95.5%) and negative predictive value of 71.4% compared with PSA and PSAD. B-MRI significantly improved sensitivity (43.2 72.7%, P = .0002) when combined with PSAD. The negative predictive value of PSA increased with B-MRI, achieving 91.7% for B-MRI and PSA for Gleason >=3 + 4. Overall accuracies of the composite equations were 81.4% (B-MRI and PSA) and 78.0% (B-MRI and PSAD). CONCLUSION: Validation with a biopsy-naive cohort demonstrates the parameter SPL performed better than PSA or PSAD alone in accurately detecting PCa. The combined use of B-MRI, PSA, and PSAD resulted in improved accuracy for detecting clinically significant PCa. PMID- 26680245 TI - Intravesical Prostatic Protrusion: A Potential Marker of Alpha-blocker Treatment Success in Patients With Benign Prostatic Enlargement. AB - OBJECTIVE: To investigate the value of anatomic and blood-flow measurements of the prostate via ultrasound in identifying medical treatment response of patients with lower urinary tract symptoms due to benign prostatic enlargement. A secondary objective of the study was to compare transabdominal-transrectal measurements. MATERIALS AND METHODS: Male patients (age range 50-80) with lower urinary tract symptoms who applied to our outpatient clinic to be diagnosed with benign prostatic enlargement that were eligible for medical management were included in the prospective study. Patients (n = 49) were administered with tamsulosin for management. At baseline evaluation, all patients underwent International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), transabdominal and transrectal ultrasound [prostate volume (PV), post-void rezidu and intravesical prostatic protrusion (IPP)], and prostate subcapsular resistive index value measurement. Follow-ups were carried out 1 and 3 months after treatment. At these time-points, patients were assessed with IPSS and uroflowmetry. RESULTS: IPP were identified to be negatively correlated with baseline Qmax values (P = .001, R = -0.485) and positively correlated with PSA (P = .013, R = 0.353) and PV (P = .003, R = 0.420). PV was related with resistive index (P = .026, R = 0.318) and PSA (P = .001, R = 0.619). Subsequent to medical treatment on the follow-ups, an overall improvement in the IPSS and Qmax was identified (P = .001). However, a negative correlation was identified in the change that occurred between IPSS and IPP (P = .004, R = -0.410). Other parameters were not correlated (P > .05) with the change in IPSS and Qmax. Transabdominal and transrectal measures were similar (P = .001). CONCLUSION: This study has shown that increased IPP values are associated with lower response to alpha-receptor specific management. Transabdominal measurements are sufficient for the evaluation compared with transrectal measurement. PMID- 26680246 TI - Following instructions in a virtual school: Does working memory play a role? AB - Accumulating evidence that working memory supports the ability to follow instructions has so far been restricted to experimental paradigms that have greatly simplified the practical demands of performing actions to instructions in everyday tasks. The aim of the present study was to investigate whether working memory is involved in maintaining information over the longer periods of time that are more typical of everyday situations that require performing instructions to command. Forty-two children 7-11 years of age completed assessments of working memory, a real-world following-instructions task employing 3-D objects, and two new computerized instruction-following tasks involving navigation around a virtual school to complete a sequence of practical spoken commands. One task involved performing actions in a single classroom, and the other, performing actions in multiple locations in a virtual school building. Verbal working memory was closely linked with all three following-instructions paradigms, but with greater association to the virtual than to the real-world tasks. These results indicate that verbal working memory plays a key role in following instructions over extended periods of activity. PMID- 26680248 TI - Corrigendum: Occurrence of chiral organochlorine compounds in the environmental matrices from King George Island and Ardley Island, west Antarctica. PMID- 26680247 TI - Physical and mental health trajectories of cancer patients and caregivers across the year post-diagnosis: a dyadic investigation. AB - OBJECTIVE: Evidence suggests interdependence between cancer patients' and their caregivers' physical and mental health. However, the extent to which caregivers' health relates to their patients' recovery, or patients' health affects their caregivers' outcomes, is largely unknown. This dyadic investigation reports the relations between cancer patients' and their caregivers' physical and mental health trajectories during the year following diagnosis. DESIGN: Ninety-two colorectal cancer patient-caregiver dyads completed questionnaires at 2, 6 and 12 months post-diagnosis. OUTCOME MEASURES: Self-reported physical and mental health using the Medical Outcomes Study Short Form Health Survey-12. RESULTS: Patients reported improved physical health over the year following their diagnosis, whereas caregivers reported declining physical health. Patients with lower mental health at diagnosis had stagnated physical health recovery. Caregivers' physical health declined most noticeably among those reporting low mental health at diagnosis and whose patients reported low physical health at diagnosis. CONCLUSION: Findings suggest targeting health interventions to cancer patients and caregivers reporting poor mental health at diagnosis may mitigate their long term physical morbidity. Limited evidence of dyadic interdependence between patients' and caregivers' physical and mental health trajectories suggests future studies are warranted to identify psychosocial and medical characteristics moderating the relations between patients' and caregivers' health. PMID- 26680249 TI - Analysis of the population genetic structure of Hb D-Los Angeles [beta121 (GH4) Glu->Gln GAA->CAA] in Denizli, Turkey; genetic diversity, historical demography and estimation of the mutation rates based on haplotype variation. AB - OBJECTIVE: Understanding the genetic origin of the Hb D-Los Angeles hemoglobin may elucidate population interactions such as movements, migrations, and environmental effects on mutation mechanisms in human biology throughout history. Our study aimed to understand the genetic origin of Hb D-Los Angeles based on haplotype data, observed in the Denizli province of Turkey. METHODS: We studied DNA samples from 40 unrelated patients with abnormal hemoglobin Hb D-Los Angeles and 59 unrelated healthy subjects from our DNA bank. Possible associated haplotypes, HWE, genetic diversity and population differentiation, population genetic structure analysis and historical-demographic analysis for the two populations were determined by Arlequin ver. 3.5. RESULTS: Molecular diversity results from the two populations show that both populations are genetically similar as far as development and expansion during the historical period. Historical gene flow results show high gene flow between the two populations. SSD and rg tests failed to reject the null hypothesis of population expansion which is consistent with unimodal distribution. Our estimated tau values show that the average time since the demographic expansion for normal and Hb D-Los Angeles populations ranged from approximately 42,000-38,000 ybp, respectively. CONCLUSIONS: Our data suggest that the Hb D-Los Angeles population originated within the normal population in Denizli, Turkey. Our results support the hypothesis that the Hb D-Los Angeles mutation may have originated in the Mediterranean area, independent from other populations such as India and China. The evaluation of such data may contribute valuable information to anthropological, paleoclimatic, archaeological, and phylogeographical approaches to human biology throughout the historical period. Am. J. Hum. Biol. 28:476-483, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26680250 TI - The Revised Screening Scale for Pedophilic Interests: Predictive and Concurrent Validity. AB - This study examined the predictive and concurrent validity of the Screening Scale for Pedophilic Interests (SSPI) and its recent revision (SSPI-2), using a large sample of 2,416 sex offenders deemed not to be in need of civil management in New York State. Both SSPI and SSPI-2 scores were significantly and positively related to sexual rearrest, but the SSPI-2 provided greater discrimination in rearrest within 5 years across possible scores. Neither measure significantly added to the prediction of sexual rearrest provided by the Static-99R. We also found evidence of concurrent validity, as both measures were positively and significantly correlated with clinician ratings of sexual preoccupation, emotional identification with children, and sexual offense-related cognitions (convergent validity), but were not significantly related to clinician ratings of self regulation problems, noncompliance with supervision, or antisocial personality (divergent validity). Overall, the results suggest that the SSPI-2 is a specific and useful screening measure of pedophilic sexual interests among sex offenders with child victims. PMID- 26680251 TI - Utility of the Static-99 and Static-99R With Latino Sex Offenders. AB - The predictive validity of the Static-99 measures with ethnic minorities in the United States has only recently been assessed with mixed results. We assessed the predictive validity of the Static-99 and Static-99R with a sample of Latino sex offenders ( N = 483) as well as with two subsamples (U.S.-born, including Puerto Rico, and non-U.S.-born). The overall sexual recidivism rate was very low (1.9%). Both the Static-99 measures were able to predict sexual recidivism for offenders born in the United States and Puerto Rico, but neither was effective in doing so for other Latino immigrants. Calibration analyses ( N = 303) of the Static-99R were consistent with the literature and provided support for the potential use of the measure with Latinos born in the United States and Puerto Rico. These findings and their implications are discussed as they pertain to the assessment of Latino sex offenders. PMID- 26680252 TI - Is Emotional Congruence With Children Associated With Sexual Offending in Pedophiles and Hebephiles From the Community? AB - Although emotional congruence with children (ECWC) is a risk factor for sexual offending against children, its conceptual validity has hardly been researched. This study aims to explore the construct of ECWC by evaluating the factor structure of the Child Identification Scale (CIS-R) and its relation to facets of sexual preference and child sexual abuse behaviors. It was hypothesized that the measure comprises consistent subscales that are differently associated with aspects of sexual preference and sexual offending against children. CIS-R data of a sample of 217 adult male pedophiles from the community were used for an exploratory principal component analysis (PCA). Group comparisons and a multinomial logistic regression analysis were conducted after including a non pedophilic control group of 22 adult men. PCA revealed a three-factor solution for the CIS-R accounting for 30% of variance. Group comparisons found differences in overall scores and the factor labeled "Attachment to Children" between subgroups of sexual age and gender preference, but not between contact, online, and non-offenders. The regression analysis showed a pedophile sexual preference and the interaction between a hebephile sexual age preference and the factor "Attachment to Children" being associated with past offending behavior. The results indicate a wish to attach to children as core feature of the CIS-R measure assessing ECWC. It is discussed whether this is an inherent feature of pedophilia or rather an independent aspect being differently distinct in pedophiles. PMID- 26680254 TI - Sperm dilution ratio affects post-thaw motility rate and velocity of Prochilodus lineatus (Characiformes) sperm. AB - There is a lack of standardization in sperm cryopreservation of aquatic organisms and, thus, a necessity of more accurate investigations in all steps of this process. In this study, the effects of sperm dilution ratio on post-thaw sperm quality of Prochilodus lineatus were evaluated. Sperm was diluted in a standard freezing medium (glucose and methyl glycol) at four different ratios (sperm to final volume = 1:5, 1:10, 1:50 or 1:100), frozen in a nitrogen vapour vessel at 170 degrees C and then stored in liquid nitrogen vessel at -196 degrees C. Post thaw motility rate and velocities (curvilinear = VCL; average path = VAP; straight line = VSL) were determined using a Computer-Assisted Sperm Analyzer (CASA) at 10 and 40 s post-activation. The highest motility rates were observed when sperm was frozen at a ratio of 1:5 (76%) and 1:10 (75%). The highest VCL (225 MUm/s) and VAP (203 MUm/s) were observed at a ratio of 1:10, while VSL was similar among samples frozen at 1:5, 1:10 and 1:50 (97-124 MUm/s). When those parameters were evaluated again 30 s later, motility decreased significantly in samples frozen at a ratio of 1:5 (57%) and 1:10 (61%), while velocities decreased significantly in all samples regardless of dilution ratio (75-85 MUm/s of VCL, 38 53 MUm/s of VAP and 25-39 MUm/s of VSL). P. lineatus sperm should be frozen at a ratio of 1:10, where both the number of loaded sperm per straw and the post-thaw quality are maximized. PMID- 26680253 TI - Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting. AB - To evaluate the feasibility of a swine model of thrombotic inferior vena cava (IVC) occlusion (IVCO) created by autologous thrombus injection with assistance of intra-caval net knitting. Sixteen pigs were included and divided into two groups: Group A (n = 10), IVCO model created by knitting a caval net followed by autologous thrombus injection; Group B (n = 6), control model created by knitting a net and normal saline injection. Venography was performed to assess each model and the associated thrombotic occlusion. The vessels were examined histologically to analyse the pathological changes postoperatively. IVCO model was successfully created in 10 animals in Group A (100%). Immediate venography showed extensive clot burden in the IVC. Postoperative venography revealed partial caval occlusion at 7 days, and complete occlusion coupled with collateral vessels at 14 days. Histologically, Group A animals had significantly greater venous wall thickening, with CD163-positive and CD3-positive cell infiltration. Recanalization channels were observed at the margins of the thrombus. By contrast, no thrombotic occlusion of the IVC was observed in Group B. The thrombotic IVCO model can be reliably established in swine. The inflammatory reaction may contribute to the caval thrombus propagation following occlusion. PMID- 26680255 TI - Characteristics and predictors of allergic rhinitis undertreatment in primary care. AB - Although allergic rhinitis is considered a raising medical problem in many countries it is often undertreated. The reasons for this phenomenon are not completely clear.The aim of this study is to evaluate factors associated with allergic rhinitis under-/no treatment.A sample of 518 allergic rhinitis patients recruited by their primary care physicians, as a part of the ARGA study, were invited to fill in a specific questionnaire regarding rhinitis symptoms, treatment, and rhinitis-related work/social disability. Chi-square test and logistic regression were performed to assess risk factors for allergic rhinitis under-/no treatment.Over one out of four patients had no treatment despite the symptoms and 13.5% were inadequately treated. Participants with asthma (OR 0.47, 95% CI 0.30-0.75) and conjunctivitis (0.44, 95% CI 0.27-0.71) were at lower risk of allergic rhinitis under-/no treatment: in asthmatics this reduction was related mainly to the concomitant asthma treatment (OR 0.19, 95% CI 0.10 0.37).Asthmatics with under-/not treated rhinitis had the highest prevalence of rhinitis-related quality of life impairment.Under-/no treatment for allergic rhinitis is still rather frequent despite the relevance of this disease. The simultaneous presence of asthma and an anti-asthmatic therapy are able to influence positively the treatment. Targeted interventions toward a better characterization and a tight follow-up of rhinitis patient without asthma are needed. PMID- 26680256 TI - Dilated cardiomyopathy following use of xenadrine EFX. AB - We describe a case of a 35-year-old man presented at the emergency room of our institution with acute onset of dyspnea and dizziness. He was a body builder and had been using Xenadrine EFX for weight loss reduction. The laboratory analyses were normal. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. Transtoracic two-dimensional color Doppler echocardiography revealed a diffuse hypokinesia with a marked decreased in systolic function and a high teledyastolic diameter. This case document the possible relation to use of Xenadrine EFX for weight loss and the recurrence of dilated cardiomyopathy. PMID- 26680258 TI - Full controlling of Fano resonances in metal-slit superlattice. AB - Controlling of the lineshape of Fano resonance attracts much attention recently due to its wide capabilities for lasing, biosensing, slow-light applications and so on. However, the controllable Fano resonance always requires stringent alignment of complex symmetry-breaking structures and thus the manipulation could only be performed with limited degrees of freedom and narrow tuning range. Furthermore, there is no report so far on independent controlling of both the bright and dark modes in a single structure. Here, we semi-analytically show that the spectral position and linewidth of both the bright and dark modes can be tuned independently and/or simultaneously in a simple and symmetric metal-slit superlattice, and thus allowing for a free and continuous controlling of the lineshape of both the single and multiple Fano resonances. The independent controlling scheme is applicable for an extremely large electromagnetic spectrum range from optical to microwave frequencies, which is demonstrated by the numerical simulations with real metal and a microwave experiment. Our findings may provide convenient and flexible strategies for future tunable electromagnetic devices. PMID- 26680260 TI - MDR3 mutation analysis: A step closer to precision medicine. PMID- 26680259 TI - AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation. AB - The mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9 dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis. PMID- 26680262 TI - Correlation of somatic mutations with outcome after FLAMSA-busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes. AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for myelodysplastic syndromes (MDS). Little is known about the prognostic impact of mutations, for example, in TP53 specifically after allo HSCT. We here describe the prognostic impact of mutations in a panel of 19 genes analyzed by amplicon-based next-generation-sequencing in a uniformly treated patient cohort. Sixty-two patients with a median age of 61 yr suffered from MDS with 0-20% bone marrow blasts. International Prognostic Score was intermediate 1 (15%) and higher (79%). Conditioning uniformly was performed using a sequential approach in which FLAMSA chemotherapy was followed by Busulfan-based conditioning. Patients mostly were transplanted from an unrelated donor (77%), and 36% of patients received a graft from a mismatched donor. Median number of mutations was 2 (range 0-6). RUNX1, GATA2, TET2, and CEBPA were the genes most frequently found mutated. TP53, a factor previously reported to confer adverse prognostic impact after allogeneic stem cell transplantation, was mutated in samples from eight patients, one of which showed a silent mutation. With an estimated 5-yr overall/disease-free survival of 48 +/- 7%/41 +/- 7%, none of the mutations analyzed showed a prognostic impact in this analysis of the largest uniformly treated cohort thus far. This especially holds true for patients with a mutation in TP53. PMID- 26680263 TI - Clinical Significance of Loss of ARID1A Expression in Colorectal and Small Intestinal Carcinoma. PMID- 26680265 TI - New Vision, New Goals for Clinical and Translational Gastroenterology. PMID- 26680264 TI - Early Comparison of Inflammatory vs. Fibrostenotic Phenotype in Eosinophilic Esophagitis in a Multicenter Longitudinal Study. AB - OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that causes esophageal remodeling and stricture formation. We compared the clinical course of symptoms, endoscopic findings, histology, and changes in phenotype over time in EoE patients with inflammatory and fibrostenotic phenotypes. METHODS: Data were obtained from EoE patients from three medical centers and followed prospectively. Endoscopic features and histology from index and follow-up endoscopies were recorded. Behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and as fibrostenotic if endoscopic findings included fixed rings or strictures. RESULTS: Two hundred and fifty-six EoE patients were included in the analysis. The mean age was 32+/ 18 years, 25% of patients were <18 years, 89% of patients were Caucasians, and 74% of patients were male. The mean duration of symptoms before diagnosis was 6.8+/-7.2 years with a follow-up of 1.7+/-1.9 years (maximum follow-up of 12 years). Fifty-four percent of patients presented with fibrostenotic EoE, whereas 46% presented with inflammatory EoE. Patients with inflammatory disease were younger than those with fibrostenotic disease (24+/-19 vs. 39+/-15 years, P<0.001). Patients with fibrostenotic disease had a longer duration of symptoms than those with inflammatory disease (8.1+/-7.7 vs. 5.3+/-6.3 years, P=0.002). Over the study period, 47 (18%) had remission of inflammatory EoE, 68 (27%) continued to have inflammatory disease, 74 (29%) continued to have fibrostenotic disease, 65 (25%) fibrostenotic patients had regression of fibrosis, and 2 patients (1%) progressed from inflammatory disease to fibrostenotic disease. Patients who had regression from their fibrostenosis were more likely than patients who continued to demonstrate fibrostenosis to have a decrease in proximal (54% vs. 32%, P<0.001) and distal (70% vs. 38%, P<0.001) eosinophilia. CONCLUSIONS: Most EoE patients maintained their phenotype or had an improvement with <1% progressing from inflammatory to fibrostenosis. This suggests that early therapeutic strategies aimed at controlling inflammation may interrupt, decrease, or prevent the remodeling fibrosis in EoE. PMID- 26680266 TI - 'I do the best I can': an in-depth exploration of the aphasia management pathway in the acute hospital setting. AB - PURPOSE: While research has begun to explore the management of aphasia across the continuum of care, to date there is little in-depth, context specific knowledge relating to the speech pathology aphasia management pathway. This research aimed to provide an in-depth understanding of the current aphasia management pathway in the acute hospital setting, from the perspective of speech pathologists. METHOD: Underpinned by a social constructivist paradigm, the researchers implemented an interpretive phenomenological method when conducting in-depth interviews with 14 Australian speech pathologists working in the acute hospital setting. Interview transcripts and interviewer field notes were subjected to a qualitative content analysis. RESULTS: Analysis identified a single guiding construct and five main categories to describe the management of aphasia in the acute hospital setting. The guiding construct, First contact with the profession, informed the entire management pathway. Five additional main categories were identified: Referral processes; Screening and assessment; Therapeutic intervention; Educational and affective counselling; and Advocacy. CONCLUSIONS: Findings suggest significant diversity in the pathways of care for people with aphasia and their families in the acute hospital setting. Additional support mechanisms are required in order to support speech pathologists to minimise the evidence-practice gap. Implications for Rehabilitation Significant diversity exists in the current aphasia management pathway for people with acute post-stroke aphasia and their families in the acute hospital setting. Mechanisms that support speech pathologists to minimise the evidence-practice gap, and consequently reduce their sense of professional dissonance, are required. PMID- 26680267 TI - The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: a systematic review and meta-analysis. AB - INTRODUCTION: Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI). AIMS: To systematically review articles reporting the prognosis of patients by Ki-67 LI and thereby improve the ability of clinicians to prognosticate for their patients. METHOD: 265 abstracts were identified relating Ki-67 and survival. After exclusion criteria were applied, 22 articles remained. Articles were excluded if they described non-human specimens, were non-English language, published prior to 2000, reported non-GEP NETs, reported subgroups selected by treatment modality or included <20 cases. Random-effects meta-analysis was used to combine studies to estimate survival proportions. RESULTS: Authors used varied methods in which to present 5-year survival, with often limited survival information. This reduced the number of studies that could be included in the meta-analysis. 5-year survival for patients with grade 1 and 2 GEP NETs were estimated to be 89% (95% CI 85% to 92%, m=12 studies, n=977 participants) and 70% (95% CI 62% to 79%, m=9, n=726), respectively. Using an alternative grade 1/2 boundary of 5%, 5-year survival rates for Ki-67<=5% and 5-20% were estimated as 89% (95% CI 84% to 94%, m=7, n=654) and 51% (95% CI 44% to 59%, m=4, n=183), respectively. For Ki-67>20%, 5-year survival was estimated to be 25% (95% CI 12% to 38%, m=10, n=208). CONCLUSIONS: Standardisation of grade boundaries has allowed us to combine data from multiple studies and amass a body of evidence linking Ki-67 and survival. PMID- 26680268 TI - A NOXA/MCL-1 Imbalance Underlies Chemoresistance of Malignant Rhabdoid Tumor Cells. AB - Malignant rhabdoid tumor (MRT) is a rare aggressive pediatric cancer characterized by inactivation of SNF5, a core subunit of SWI/SNF complexes. Previously, we showed that SNF5 contributes to transcriptional activation of NOXA, a pro-apoptotic protein that binds and inhibits the anti-apoptotic protein MCL-1. In this study, we found that NOXA expression was downregulated in MRT cell lines as well as in clinical MRT samples and that ectopically expressed NOXA bound MCL-1 and increased the sensitivity of MRT cell lines to doxorubicin (DOX) by promoting apoptosis. Consistent with this finding, knockdown of MCL-1 in MRT cell lines induced apoptosis and increased DOX sensitivity in MRT cells, and the MCL-1 inhibitor TW-37 synergized with DOX to induce MRT cell death. Our results suggest that modulation of the NOXA/MCL-1 pathway may be a potential strategy for the treatment of patients with MRT. J. Cell. Physiol. 231: 1932-1940, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26680269 TI - An adaptive genetic algorithm for selection of blood-based biomarkers for prediction of Alzheimer's disease progression. AB - BACKGROUND: Alzheimer's disease is a multifactorial disorder that may be diagnosed earlier using a combination of tests rather than any single test. Search algorithms and optimization techniques in combination with model evaluation techniques have been used previously to perform the selection of suitable feature sets. Previously we successfully applied GA with LR to neuropsychological data contained within the The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, to select cognitive tests for prediction of progression of AD. This research addresses an Adaptive Genetic Algorithm (AGA) in combination with LR for identifying the best biomarker combination for prediction of the progression to AD. RESULTS: The model has been explored in terms of parameter optimization to predict conversion from healthy stage to AD with high accuracy. Several feature sets were selected - the resulting prediction moddels showed higher area under the ROC values (0.83-0.89). The results has shown consistency with some of the medical research reported in literature. CONCLUSION: The AGA has proven useful in selecting the best combination of biomarkers for prediction of AD progression. The algorithm presented here is generic and can be extended to other data sets generated in projects that seek to identify combination of biomarkers or other features that are predictive of disease onset or progression. PMID- 26680270 TI - [Stomach cancer: a descriptive study of 101 cases at the gastrointestinal endoscopy center at Aristide Le Dantec University Hospital]. AB - INTRODUCTION: Stomach cancer is a real public health problem in Black Africa. We report its epidemiological, endoscopic, and histological aspects, as observed in our gastrointestinal endoscopy center at Aristide Le Dantec University Hospital in Dakar (Senegal). PATIENTS AND METHODS: This retrospective study covered the 5 year period from January 1, 2006, to December 31, 2010 and included all patients with stomach cancer confirmed by anatomo-pathological examination. We collected data about age, sex, indications for the examination, and description of the gastric lesions and any other associated lesions from the upper GI endoscopy reports. We also recorded information from the histological reports of all lesions. RESULTS: The study included 101 patients. The incidence of gastric cancer was 20 cases/year. Patients' mean age was 58 years [range: 24-83]. The sex ratio was 2.48. The main indications for the upper GI endoscopy were epigastralgia (33.3%), vomiting (26.1%), and tumoral hepatomegalia (10.81%). The examination found mainly ulcerative and protruded lesions (59.40%). Other types of lesions associated with the tumor were esophageal candidiasis (34.6%), peptic esophagitis (25%), and gastroesophageal junction incompetence (25%). The tumor was located in the antrum in 68% of the cases and was an adenocarcinoma in 83.2%. CONCLUSION: A cancer register to determine the characteristics and prevalence of stomach cancer in Senegal would be useful. The link with Helicobacter pylori requires further study. PMID- 26680271 TI - Prediction of linear B-cell epitopes of hepatitis C virus for vaccine development. AB - BACKGROUND: High genetic heterogeneity in the hepatitis C virus (HCV) is the major challenge of the development of an effective vaccine. Existing studies for developing HCV vaccines have mainly focused on T-cell immune response. However, identification of linear B-cell epitopes that can stimulate B-cell response is one of the major tasks of peptide-based vaccine development. Owing to the variability in B-cell epitope length, the prediction of B-cell epitopes is much more complex than that of T-cell epitopes. Furthermore, the motifs of linear B cell epitopes in different pathogens are quite different (e. g. HCV and hepatitis B virus). To cope with this challenge, this work aims to propose an HCV customized sequence-based prediction method to identify B-cell epitopes of HCV. RESULTS: This work establishes an experimentally verified dataset comprising the B-cell response of HCV dataset consisting of 774 linear B-cell epitopes and 774 non B-cell epitopes from the Immune Epitope Database. An interpretable rule mining system of B-cell epitopes (IRMS-BE) is proposed to select informative physicochemical properties (PCPs) and then extracts several if-then rule-based knowledge for identifying B-cell epitopes. A web server Bcell-HCV was implemented using an SVM with the 34 informative PCPs, which achieved a training accuracy of 79.7% and test accuracy of 70.7% better than the SVM-based methods for identifying B-cell epitopes of HCV and the two general-purpose methods. This work performs advanced analysis of the 34 informative properties, and the results indicate that the most effective property is the alpha-helix structure of epitopes, which influences the connection between host cells and the E2 proteins of HCV. Furthermore, 12 interpretable rules are acquired from top-five PCPs and achieve a sensitivity of 75.6% and specificity of 71.3%. Finally, a conserved promising vaccine candidate, PDREMVLYQE, is identified for inclusion in a vaccine against HCV. CONCLUSIONS: This work proposes an interpretable rule mining system IRMS-BE for extracting interpretable rules using informative physicochemical properties and a web server Bcell-HCV for predicting linear B-cell epitopes of HCV. IRMS-BE may also apply to predict B-cell epitopes for other viruses, which benefits the improvement of vaccines development of these viruses without significant modification. Bcell-HCV is useful for identifying B-cell epitopes of HCV antigen to help vaccine development, which is available at http://e045.life.nctu.edu.tw/BcellHCV. PMID- 26680272 TI - The Generally Useful Estimate of Solvent Systems (GUESS) method enables the rapid purification of methylpyridoxine regioisomers by countercurrent chromatography. AB - The TLC-based Generally Useful Estimate of Solvent Systems (GUESS) method was employed for countercurrent chromatography solvent system selection, in order to separate the three synthetic isomers: 3-O-methylpyridoxine, 4'-O-methylpyridoxine (ginkgotoxin), and 5'-O-methylpyridoxine. The Rf values of the three isomers indicated that ChMWat+2 (chloroform-methanol-water 10:5:5, v/v/v) was appropriate for the countercurrent separation. The isomer separation was highly selective and demonstrated that the TLC-based GUESS method can accelerate solvent system selection for countercurrent separation. Accordingly, the study re-emphasizes the practicality of TLC as a tool to facilitate the rapid development of new countercurrent and centrifugal partition chromatography methods for this solvent system. Purity and structure characterization of all samples was performed by quantitative (1)H NMR. PMID- 26680273 TI - Selenocysteine: Wherefore Art Thou? AB - Selenocysteine is a naturally occurring proteogenic amino acid that is encoded in the genomic sequence of relatively abundant proteins in many of the model species commonly used for biomedical research. On the basis of an analysis of publicly available proteomics information, it was discovered that peptides containing selenocysteine were not being identified in tandem mass spectrometry proteomics data. Once the chemical basis for this exclusion was understood, a simple alteration in search parameters led to the confident identification of selenocysteine containing peptides from existing proteomics data, with no change in experimental protocols required. PMID- 26680274 TI - Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp(3)) H Functionalization under Mild Reaction Conditions. AB - Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp(3))-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp(3))-H functionalization reaction effectively with high regio- and chemoselectivity. PMID- 26680275 TI - Atrial Function after the Atrial Switch Operation for Transposition of the Great Arteries: Comparison with Arterial Switch and Normals by Cardiovascular Magnetic Resonance. AB - OBJECTIVES: The atria serve as reservoir, conduit, and active pump for ventricular filling. The performance of the atrial baffles after atrial switch repair for transposition of the great arteries may be abnormal and impact the function of the systemic right ventricle. We sought to assess atrial function in patients after atrial repair in comparison to patients after arterial switch repair (ASO) and to controls. METHODS: Using magnetic resonance imaging, atrial volumes and functional parameters were measured in 17 patients after atrial switch repair, 9 patients after ASO and 10 healthy subjects. RESULTS: After the atrial switch operation, the maximum volume of the pulmonary venous atrium was significantly enlarged, but not of the systemic venous atrium. In both patients groups, independently from the surgical technique used, the minimum atrial volumes were elevated, which resulted in a decreased total empting fraction compared with controls (P < .01). The passive empting volume was diminished for right atrium, but elevated for left atrium after atrial switch and normal for left atrium after ASO; however, the passive empting fraction was diminished for both right atrium and left atrium after both operations (P < .01). The active empting volume was the most affected parameter in both atria and both groups and active empting fractions were highly significantly reduced compared with controls. CONCLUSION: Atrial function is abnormal in all patients, after atrial switch and ASO repair. The cyclic volume changes, that is, atrial filling and empting, are reduced when compared with normal subjects. Thus, the atria have lost part of their capacity to convert continuous venous flow into a pulsatile ventricular filling. The function of the pulmonary venous atrium, acting as preload for the systemic right ventricle, after atrial switch is altered the most. PMID- 26680276 TI - A safety vs efficiency trade-off identified in the hydraulic pathway of grass leaves is decoupled from photosynthesis, stomatal conductance and precipitation. AB - A common theme in plant physiological research is the trade-off between stress tolerance and growth; an example of this trade-off at the tissue level is the safety vs efficiency hypothesis, which suggests that plants with the greatest resistance to hydraulic failure should have low maximum hydraulic conductance. Here, we quantified the leaf-level drought tolerance of nine C4 grasses as the leaf water potential at which plants lost 50% (P50 * RR ) of maximum leaf hydraulic conductance (Ksat ), and compared this trait with other leaf-level and whole-plant functions. We found a clear trade-off between Ksat and P50 * RR when Ksat was normalized by leaf area and mass (P = 0.05 and 0.01, respectively). However, no trade-off existed between P50 * RR and gas-exchange rates; rather, there was a positive relationship between P50 * RR and photosynthesis (P = 0.08). P50 * RR was not correlated with species distributions based on precipitation (P = 0.70), but was correlated with temperature during the wettest quarter of the year (P < 0.01). These results suggest a trade-off between safety and efficiency in the hydraulic system of grass leaves, which can be decoupled from other leaf level functions. The unique physiology of C4 plants and adaptations to pulse driven systems may provide mechanisms that could decouple hydraulic conductance from other plant functions. PMID- 26680277 TI - Estimating rotavirus vaccine effectiveness in Japan using a screening method. AB - Rotavirus gastroenteritis is a highly contagious, acute viral disease that imposes a significant health burden worldwide. In Japan, rotavirus vaccines have been commercially available since 2011 for voluntary vaccination, but vaccine coverage and effectiveness have not been evaluated. In the absence of a vaccination registry in Japan, vaccination coverage in the general population was estimated according to the number of vaccines supplied by the manufacturer, the number of children who received financial support for vaccination, and the size of the target population. Patients with rotavirus gastroenteritis were identified by reviewing the medical records of all children who consulted 6 major hospitals in Saga Prefecture with gastroenteritis symptoms. Vaccination status among these patients was investigated by reviewing their medical records or interviewing their guardians by telephone. Vaccine effectiveness was determined using a screening method. Vaccination coverage increased with time, and it was 2-times higher in municipalities where the vaccination fee was supported. In the 2012/13 season, vaccination coverage in Saga Prefecture was 14.9% whereas the proportion of patients vaccinated was 5.1% among those with clinically diagnosed rotavirus gastroenteritis and 1.9% among those hospitalized for rotavirus gastroenteritis. Thus, vaccine effectiveness was estimated as 69.5% and 88.8%, respectively. This is the first study to evaluate rotavirus vaccination coverage and effectiveness in Japan since vaccination began. PMID- 26680279 TI - A new peak detection algorithm for MALDI mass spectrometry data based on a modified Asymmetric Pseudo-Voigt model. AB - BACKGROUND: Mass Spectrometry (MS) is a ubiquitous analytical tool in biological research and is used to measure the mass-to-charge ratio of bio-molecules. Peak detection is the essential first step in MS data analysis. Precise estimation of peak parameters such as peak summit location and peak area are critical to identify underlying bio-molecules and to estimate their abundances accurately. We propose a new method to detect and quantify peaks in mass spectra. It uses dual tree complex wavelet transformation along with Stein's unbiased risk estimator for spectra smoothing. Then, a new method, based on the modified Asymmetric Pseudo-Voigt (mAPV) model and hierarchical particle swarm optimization, is used for peak parameter estimation. RESULTS: Using simulated data, we demonstrated the benefit of using the mAPV model over Gaussian, Lorentz and Bi-Gaussian functions for MS peak modelling. The proposed mAPV model achieved the best fitting accuracy for asymmetric peaks, with lower percentage errors in peak summit location estimation, which were 0.17% to 4.46% less than that of the other models. It also outperformed the other models in peak area estimation, delivering lower percentage errors, which were about 0.7% less than its closest competitor - the Bi-Gaussian model. In addition, using data generated from a MALDI-TOF computer model, we showed that the proposed overall algorithm outperformed the existing methods mainly in terms of sensitivity. It achieved a sensitivity of 85%, compared to 77% and 71% of the two benchmark algorithms, continuous wavelet transformation based method and Cromwell respectively. CONCLUSIONS: The proposed algorithm is particularly useful for peak detection and parameter estimation in MS data with overlapping peak distributions and asymmetric peaks. The algorithm is implemented using MATLAB and the source code is freely available at http://mapv.sourceforge.net. PMID- 26680280 TI - Occipitocervical Fetus in Fetu with Extracalvarial Extension: A Case Report. AB - Fetus in fetu (FIF) is an extremely rare congenital anomaly in the pediatric age group. It is defined by the presence of an axial skeleton and well-formed internal organs in a fetiform mass. Only about 15 cases of intracranial FIF have been reported in the literature worldwide. We report a case of temporo occipitocervical FIF. This 7-month-old female child presented to us with occipital swelling that she had had since birth. A soft swelling was palpable in the retroauricular region with extension into the neck. A few bony parts were palpable in the swelling. Imaging was suggestive of a multiseptate mass lesion in the right occipital region with intracranial, intraspinal and extracranial components. The patient underwent exploration and excision of the extracranial mass and retromastoid suboccipital craniectomy and decompression of the intracranial component. Different parts, such as a terminal ileum, cecum, appendix, femur, humerus and vertebral body, were identified within the mass. This case meets Willis' criteria as well as 4/5 criteria stated by Spencer for the diagnosis of this condition. To the best of our knowledge, this is the first reported case of temporo-occipitocervical FIF with a well-defined embryological spectrum. This also supports Spencer's hypothesis of abnormal twinning. PMID- 26680278 TI - Racial differences in associations between baseline patterns of radiographic osteoarthritis and multiple definitions of progression of hip osteoarthritis: the Johnston County Osteoarthritis Project. AB - BACKGROUND: To identify baseline radiographic features that predict hip osteoarthritis (HOA) progression, and to explore differences in these associations by race. METHODS: Radiographs from the community-based Johnston County OA Project were scored using Kellgren-Lawrence (KL) grade and for presence and location of joint space narrowing (JSN), osteophytes, and subchondral changes. Associations between these features and HOA progression (increase of at least 1 KL grade, interval hip replacement, range of motion [ROM, a reduction of >=10 degrees in internal rotation], or disability [increase of >=0.2 in Health Assessment Questionnaire scores], or Any of these) were assessed using logistic regression, adjusting for age, gender, race, hip injury, BMI, education, smoking and follow-up time, accounting for multiple comparisons. Race interactions were assessed and analyses stratified as indicated. RESULTS: The sample (n = 1,422) included 40 % men and 26 % African American (AA) participants, with mean age 61 years and BMI 29 kg/m(2). The baseline frequency of radiographic hip OA (RHOA) between Caucasians and AAs was similar (23 %), although some radiographic features differed. AAs were more likely to have progression defined by ROM or disability or Any progression; Caucasians were more likely to have RHOA progression. JSN, subchondral sclerosis, and medial osteophytes were associated with increased RHOA progression overall; JSN was associated with disability progression only in AAs, while lateral osteophytes were associated with ROM progression only in Caucasians. CONCLUSIONS: AAs and Caucasians exhibited differences in the radiographic presentation and progression patterns of HOA, with AAs reporting progressive pain and disability, while Caucasians had more RHOA progression. PMID- 26680281 TI - HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland. AB - Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16 93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche((r)) linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n = 684) and 5.1% for HPV-18 (n = 93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n = 283), 34.1% CIN II (n = 145), 18.7% of CIN III (n = 146), 7.8% of SCC (n = 5), and 35.7% of AC (n = 5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines. PMID- 26680282 TI - Commentary to "Proximal hypospadias: A persistent challenge: Single institution outcome analysis of 3 surgical techniques over a 10-year period". PMID- 26680283 TI - Febuxostat Prevents Renal Interstitial Fibrosis by the Activation of BMP-7 Signaling and Inhibition of USAG-1 Expression in Rats. AB - BACKGROUND: Renal interstitial fibrosis (RIF) is a common pathology associated with end-stage renal diseases. The activation of bone morphogenetic protein-7 (BMP-7)-Smad1/5/8 pathway seems to alleviate RIF. Uterine sensitization associated gene-1 (USAG-1), a kidney-specific BMPs antagonist, is associated with the development and prognosis of several renal diseases. Febuxostat is a xanthine oxidase inhibitor that can attenuate the renal dysfunction of patients. The purpose of this study was to investigate the effects of febuxostat on renal fibrosis and to clarify the mechanisms underlying these effects. METHODS: Rats were randomly divided into 6 groups termed a sham-operated group, a unilateral ureteral obstruction (UUO) group, 3 doses of febuxostat groups (low, intermediate and high doses) and a sham group treated with high-dose febuxostat. After 14 days, renal function, relative kidney weight, accumulation of glycogen and collagens were examined by different methods. Expression of alpha-SMA, transforming growth factor-beta1 (TGF-beta1), BMP-7 and USAG-1 was detected by western blotting and RT-PCR, respectively. The phosphorylation level of Smad1/5/8 was also quantified by western blotting. RESULTS: The renal function was declined, and large amounts of glycogen and collagens were deposited in the kidneys of UUO rats compared with the rats in the sham group. Besides, expression of alpha-SMA and USAG-1 in these kidneys was elevated, and the TGF-beta1 was also activated, while the BMP-7-Smad1/5/8 pathway was inhibited. Febuxostat reversed the changes stated earlier, exhibiting protective effects on RIF induced by UUO. CONCLUSION: Febuxostat was able to attenuate RIF caused by UUO, which was associated with the activation of BMP-7-Smad1/5/8 pathway and the inhibition of USAG-1 expression in the kidneys of UUO rats. PMID- 26680284 TI - The relation between societal factors and different forms of prejudice: A cross national approach on target-specific and generalized prejudice. AB - The goal of this paper was to investigate the generalizability of prejudice across contexts by analyzing associations between different types of prejudice in a cross-national perspective and by investigating the relation between country specific contextual factors and target-specific prejudices. Relying on the European Social Survey (2008), results indicated that prejudices were indeed positively associated, confirming the existence of a generalized prejudice component. Next to substantial cross-national differences in associational strength, also within country variance in target-specific associations was observed. This suggested that the motivations for prejudice largely vary according to the intergroup context. Two aspects of the intergroup context - economic conditions and cultural values - showed to be related to generalized and target-specific components of prejudice. Future research on prejudice and context should take an integrative approach that considers both the idea of generalized and specific prejudice simultaneously. PMID- 26680285 TI - From the general to the specific: How social trust motivates relational trust. AB - When people form beliefs about the trustworthiness of others with respect to particular matters (i.e., when individuals trust), theory suggests that they rely on preexistent cognitive schemas regarding the general cooperativeness of individuals and organizations (i.e., social trust). In spite of prior work, the impact of social trust on relational trust-or what Russell Hardin (2002) calls trust as a three-part relation where actor A trusts actor B with reference to matter Y-is not well established. Four vignette experiments were administered to Amazon.com Mechanical Turk workers (N = 1388 and N = 1419) and to public university undergraduate students (N = 995 and N = 956) in order to investigate the relationship between social trust and relational trust. Measures of general social trust and particular social trust produced statistically equivalent effects that were positively associated with relational trust. Political trust, however, was statistically unrelated to relational trust. These results support the idea that people rely on schemas and stereotypes concerned with the general cooperativeness and helpfulness of others when forming beliefs about another person's trustworthiness with respect to a particular matter at hand. PMID- 26680286 TI - Gender and homosexuality attitudes across religious groups from the 1970s to 2014: Similarity, distinction, and adaptation. AB - This study uses General Social Survey data to compare gender and homosexuality across American religious groups from the 1970s to 2014, examining three possible patterns for how evangelical attitudes relate to those of other groups: (1) they are similar; (2) they are different, but move together over time; (3) they are different and converge or diverge over time. Evangelical gender attitudes regarding work and family issues are more conservative than those of all other groups, but are adaptive to broad trends, changing at a rate similar to those of other groups. Evangelical attitudes toward the morality of homosexuality and same sex marriage are more conservative than those of all other religious groups, and their rate of change is slower over time. Separate trends on the two issues suggest that gender and sexuality attitude change is decoupled, especially among evangelicals who are adapting more on gender while increasingly distinguishing themselves on same-sex relationships. A three-stage process of religious tension appears to characterize evangelical identity-building: (1) similarity, (2) distinction, and (3) adaptation. PMID- 26680287 TI - The specter of discrimination: Fear of interpersonal racial discrimination among adolescents in Chicago. AB - This analysis examines fear of interpersonal racial discrimination among Black, Hispanic, and White adolescents. The extent and correlates of these concerns are examined using survey data from the Project for Human Development in Chicago Neighborhoods. Borrowing from the fear-of-crime literature, the contact hypothesis, and group threat theory, several hypotheses are developed linking discrimination fear to direct personal experience with discrimination, indirect or vicarious experience, and environmental signals of discrimination. Results show that about half of Blacks and Hispanics have feared discrimination in the past year. Multivariate results indicate that fear is most likely if one has experienced victimization first-hand and when one's parent is affected by discrimination. Further, a larger presence neighborhood outgroups produces greater fear. Overall, discrimination fear constitutes an additional obstacle for minority adolescents as they transition to adulthood. The phenomenon warrants increased scholarly attention and represents a fruitful avenue for future research. PMID- 26680288 TI - Neither bridging nor bonding: A test of socialization effects by ethnically diverse voluntary associations on participants' inter-ethnic tolerance, inter ethnic trust and intra-ethnic belonging. AB - The distinction between bridging and bonding associations is a cornerstone of social capital research. Nevertheless, this study is the first to provide a direct test of the socialization mechanism that supposedly causes ethnically mixed (bridging) associations to generate interethnic tolerance and trust, and homogenous (bonding) associations to cement self-affirming identities. This multilevel analysis of the Citizenship, Involvement & Democracy (CID) 1999/2000 survey data on Mannheim (Germany), Enschede (the Netherlands), and Aberdeen (Scotland) covers 3166 active participants in 645 associations. The CID includes objective, exogenous measures of each association's composition and aim. Socialization and self-selection effects are pulled apart through interactions with detailed measures of associational involvement. The results display no evidence for (diverse and homogenous) associations as socializing agents. Although inter-ethnic tolerance is higher in ethnically diverse associations, this should be attributed to self-selection effects. PMID- 26680289 TI - Tract- and county-level income inequality and individual risk of obesity in the United States. AB - OBJECTIVES: We tested three alternative hypotheses regarding the relationship between income inequality and individual risk of obesity at two geographical scales: U.S. Census tract and county. METHODS: Income inequality was measured by Gini coefficients, created from the 2000 U.S. Census. Obesity was clinically measured in the 2003-2008 National Health and Nutrition Examination Survey (NHANES). The individual measures and area measures were geo-linked to estimate three sets of multi-level models: tract only, county only, and tract and county simultaneously. Gender was tested as a moderator. RESULTS: At both the tract and county levels, higher income inequality was associated with lower individual risk of obesity. The size of the coefficient was larger for county-level Gini than for tract-level Gini; and controlling income inequality at one level did not reduce the impact of income inequality at the other level. Gender was not a significant moderator for the obesity-income inequality association. CONCLUSIONS: Higher tract and county income inequality was associated with lower individual risk of obesity, indicating that at least at the tract and county levels and in the context of cross-sectional data, the public health goal of reducing the rate of obesity is in line with anti-poverty policies of addressing poverty through mixed income development where neighborhood income inequality is likely higher than homogeneous neighborhoods. PMID- 26680290 TI - The dynamics of radical right-wing populist party preferences and perceived group threat: A comparative panel analysis of three competing hypotheses in the Netherlands and Germany. AB - Existing cross-sectional research considers citizens' preferences for radical right-wing populist (RRP) parties to be centrally driven by their perception that immigrants threaten the well-being of the national ingroup. However, longitudinal evidence for this relationship is largely missing. To remedy this gap in the literature, we developed three competing hypotheses to investigate: (a) whether perceived group threat is temporally prior to RRP party preferences, (b) whether RRP party preferences are temporally prior to perceived group threat, or (c) whether the relation between perceived group threat and RRP party preferences is bidirectional. Based on multiwave panel data from the Netherlands for the years 2008-2013 and from Germany spanning the period 1994-2002, we examined the merits of these hypotheses using autoregressive cross-lagged structural equation models. The results show that perceptions of threatened group interests precipitate rather than follow citizens' preferences for RRP parties. These findings help to clarify our knowledge of the dynamic structure underlying RRP party preferences. PMID- 26680291 TI - Education and fertility decline in China during transitional times: A cohort approach. AB - We examine the effect of education on birth outcomes in China during the period of economic transition and large-scale changes in mass education and population control measures. Retrospective micro data from the 2008 Chinese General Social Survey and discrete time event history analysis are used to examine the fertility history of several cohorts of women born between 1945 and 1968. We observed births at different parities, distinguishing the education effect across cohorts and rural/urban sectors. We found differences across cohorts consistent with unique features of the Chinese context, such as the radical egalitarian era of educational expansion, and the Reform Era. We also found that despite the increase in some education levels across cohorts (e.g., junior high school in rural areas), birth chances were more likely to be concentrated among less educated women, suggesting the impact of factors related to returns to education and hence the desire for children. PMID- 26680292 TI - Participation in national celebrations and commemorations: The role of socialization and nationalism in the Dutch context. AB - National celebrations and commemorations are believed to increase national cohesion. It is unknown however who participates in these activities. In this contribution, we address to what extent socialization by the parents and school, and integration into religious intermediary groups affect participation in national celebrations and commemorations. With the strong reference to the relevance of the nation in national days, we also hypothesize about the association between nationalist attitudes and national day participation. We chose the Netherlands as test case, with its institutionalized national days to remember war victims, to celebrate freedom and to celebrate the Monarchy. Relying on a national survey (LISS; N = 4559), our findings show that the transmission of parental behaviours is crucial for taking part in national celebrations and commemorative events. Schooling and integration in religious groups only affect specific forms of national celebrations and commemorations. In line with US based research on flagging the Stars and Stripes, we find that national day participation in this European country is affected by patriotic attitudes rather than by chauvinistic attitudes. PMID- 26680293 TI - The role of occupational attributes in gender earnings inequality, 1970-2010. AB - Grounded in the research on the important role of social structures in forming gender inequalities, this study examines the effect of occupational attributes on the gender earnings gap over four decades. Using the IPUMS-USA from 1970 to 2010, the paper shows that occupational attributes cannot be reduced to the aggregate attributes of their individual incumbents. Rather, the effect of occupations on the gender earnings gap goes far beyond both the distributive role of occupational segregation and the effect of individual wage-related characteristics. Furthermore, occupations not only explain a significant portion of net gender pay gaps, but have also contributed to the narrowing of the gaps over the past several decades, as occupational attributes that favor women's pay have become more dominant over time. PMID- 26680294 TI - The effectiveness of apprenticeship training: A within-track comparison of workplace-based and school-based vocational training in Hungary. AB - Although apprenticeship training has been praised for its effectiveness in easing the transition of non-college-bound students from school to work, most studies rely on cross-country or cross-track comparisons. This study compares apprenticeship training students with non-apprentices within educational track in a relatively uncoordinated and decentralized institutional setting. Using a rich database and a unique set of observable individual-level characteristics as well as local labor market fixed effects to control for the potential selection bias, the results show that there are no significant differences in employment opportunities between apprentices and non-apprentices within just a year after graduation. This might be due to the failure of the Hungarian firms to enhance the skills of apprentices and thus increase their chances of entering the labor market compared to their school-trained peers. However, some immediate positive effect of apprenticeship training within sub-populations is apparent, which are likely to be the result of screening. PMID- 26680295 TI - Grandparents' resources and grandchildren's schooling: Does grandparental involvement moderate the grandparent effect? AB - Recent studies have argued that grandparents have a direct effect on grandchildren's achievements, net of parental resources. However, little is known about the underlying mechanisms. One explanation is that grandchildren can benefit from the cultural resources that grandparents transmit to their grandchildren. If this is the case, one would expect strong effects in families where grandparents are highly involved in the lives of their grandchildren and weak or no effects in other families. Using new nationally representative survey data on three generations in the Netherlands, we examine if and how grandchildren's educational attainment is affected by three grandparental resources: education, occupational status, and cultural resources. We explore how these effects vary by the strength of the tie between grandparent and grandchild. We find no evidence for a main direct grandparental effect, nor do we find interactions with the strength of the tie between grandparent and grandchild. These null-findings are discussed in light of the mixed body of evidence that has been accumulated in the literature and contemporary theorizing on grandparenting. PMID- 26680296 TI - The declining influence of family background on educational attainment in Australia: The role of measured and unmeasured influences. AB - The paper examines changes in the influence of family background, including socioeconomic and social background variables on educational attainment in Australia for cohorts born between 1890 and 1982. We test hypotheses from modernization theory on sibling data using random effects models and find: (i) substantial declines in the influence of family background on educational attainment (indicated by the sibling intraclass correlations); (ii) declines in the effects of both economic and cultural socioeconomic background variables; (iii) changes in the effects of some social background variables (e.g., family size); (iv) and declines in the extent that socioeconomic and social background factors account for variation in educational attainment. Unmeasured family background factors are more important, and proportionally increasingly so, for educational attainment than the measured socioeconomic and social background factors analyzed. Fixed effects models showed steeper declines in the effects of socioeconomic background variables than in standard analyses suggesting that unmeasured family factors associated with socioeconomic background obscure the full extent of the decline. PMID- 26680297 TI - A Note on the Noncollapsibility of Rate Differences and Rate Ratios. AB - It is well known that the odds ratio is noncollapsible, in the sense that conditioning on a covariate that is related to the outcome typically changes the size of the odds ratio, even if this covariate is unrelated to the exposure. The risk difference and risk ratio do not have this peculiar property; we say that the risk difference and risk ratio are collapsible. However, noncollapsibility is not unique for the odds ratio; the rate difference and rate ratio are generally noncollapsible as well. This may seem paradoxical, since the rate can be viewed as a risk per unit time, and thus one would naively suspect that the rate difference/ratio should inherit collapsibility from the risk difference/ratio. Adding to the confusion, it was recently shown that the exposure coefficient in the Aalen additive hazards model is collapsible. This may seem to contradict the fact that the rate difference is generally noncollapsible, since the exposure coefficient in the Aalen additive hazards model is a rate difference. In this article, we use graphical arguments to explain why the rate difference/ratio does not inherit collapsibility from the risk difference/ratio. We also explain when and why the exposure coefficient in the Aalen additive hazards model is collapsible. PMID- 26680298 TI - Correlation of the content of hepatitis B core antigen in peripheral blood mononuclear cells with HBV virus load. AB - The dysfunction of peripheral blood mononuclear cell (PBMC) plays an important role in hepatitis B virus (HBV) chronic infection and tolerance. This study is aimed to explore the changes of expression and distribution of Hepatitis B virus core antigen (HBcAg) in the PBMCs of patients infected with chronic hepatitis B virus by using confocal laser scanning microscopy (CLSM). The levels of HBcAg in PBMCs were correlated with the HBV load in serum, and the change of HBcAg distribution in different PBMC organelles may represent various HBV infection states. HBcAg was mainly distributed in the nuclei of PBMC in the cases of immune tolerance and no inflammatory activity. Taken together, our data suggest that the measurement of HBcAg and its distribution in PBMCs using CLSM may serve as an alternative approach to monitor HBV load and the immune states of HBV infection with ease of using and improved sensitivity. PMID- 26680299 TI - Serum ethanolamine plasmalogens improve detection of cognitive impairment among elderly with high excretion levels of urinary myo-inositol: A cross-sectional study. AB - BACKGROUND: Several reports have implicated myo-inositol (MI) in myelin formation. We hypothesized that MI is involved in this process through facilitating the biosynthesis of ethanolamine plasmalogens (PlsEtns), which are the major component of myelin membranes, and essential for myelin formation and function. Excessive MI urinary excretion possibly causes PlsEtn deficiency, leading to demyelinating diseases including dementia. METHODS: We examined the association between cognitive impairment, serum levels of PlsEtn, and baseline levels of urinary MI excretion, in the enrollment of 55 memory clinic outpatients and 107 cognitively normal elderly. RESULTS: Serum PlsEtns were independently associated with cognitive impairment, and significantly reduced in memory clinic outpatients, especially in those with high urinary MI, as compared to normal elderly. On the other hand, there was no direct association between urinary MI and cognitive impairment, but urinary MI was significantly associated with serum hemoglobin A1c and amyloid beta 1-40. The interaction between PlsEtn and urinary MI for cognitive impairment was statistically confirmed, and their combined usage improved diagnosis of cognitive impairment. CONCLUSIONS: We proposed the involvement of MI and PlsEtn in cognitive impairment pathology. In conclusion, serum PlsEtn may be useful in detecting cognitive decline among elderly with hyperglycemia. PMID- 26680301 TI - The prenucleosome, a stable conformational isomer of the nucleosome. AB - Chromatin comprises nucleosomes as well as nonnucleosomal histone-DNA particles. Prenucleosomes are rapidly formed histone-DNA particles that can be converted into canonical nucleosomes by a motor protein such as ACF. Here we show that the prenucleosome is a stable conformational isomer of the nucleosome. It consists of a histone octamer associated with ~ 80 base pair (bp) of DNA, which is located at a position that corresponds to the central 80 bp of a nucleosome core particle. Monomeric prenucleosomes with free flanking DNA do not spontaneously fold into nucleosomes but can be converted into canonical nucleosomes by an ATP-driven motor protein such as ACF or Chd1. In addition, histone H3K56, which is located at the DNA entry and exit points of a canonical nucleosome, is specifically acetylated by p300 in prenucleosomes relative to nucleosomes. Prenucleosomes assembled in vitro exhibit properties that are strikingly similar to those of nonnucleosomal histone-DNA particles in the upstream region of active promoters in vivo. These findings suggest that the prenucleosome, the only known stable conformational isomer of the nucleosome, is related to nonnucleosomal histone-DNA species in the cell. PMID- 26680300 TI - Evolution and function of genomic imprinting in plants. AB - Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and confirmed DNA and histone methylation as key regulators of plant imprinting. However, the biological roles of the vast majority of imprinted plant genes are unknown, and the evolutionary forces shaping plant imprinting remain rather opaque. Here, we review the mechanisms of plant genomic imprinting and discuss theories of imprinting evolution and biological significance in light of recent findings. PMID- 26680302 TI - Rev1 promotes replication through UV lesions in conjunction with DNA polymerases eta, iota, and kappa but not DNA polymerase zeta. AB - Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polzeta, and Polzeta together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Poleta, Poliota, and Polkappa but is not required for TLS by Polzeta. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Poleta, Poliota, and Polkappa, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans. PMID- 26680303 TI - Erythropoietin and IGF-1 signaling synchronize cell proliferation and maturation during erythropoiesis. AB - Tight coordination of cell proliferation and differentiation is central to red blood cell formation. Erythropoietin controls the proliferation and survival of red blood cell precursors, while variations in GATA-1/FOG-1 complex composition and concentrations drive their maturation. However, clear evidence of cross-talk between molecular pathways is lacking. Here, we show that erythropoietin activates AKT, which phosphorylates GATA-1 at Ser310, thereby increasing GATA-1 affinity for FOG-1. In turn, FOG-1 displaces pRb/E2F-2 from GATA-1, ultimately releasing free, proproliferative E2F-2. Mice bearing a Gata-1(S310A) mutation suffer from fatal anemia when a compensatory pathway for E2F-2 production involving insulin-like growth factor-1 (IGF-1) signaling is simultaneously abolished. In the context of the GATA-1(V205G) mutation resulting in lethal anemia, we show that the Ser310 cannot be phosphorylated and that constitutive phosphorylation at this position restores partial erythroid differentiation. This study sheds light on the GATA-1 pathways that synchronize cell proliferation and differentiation for tissue homeostasis. PMID- 26680304 TI - Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing. AB - Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons. PMID- 26680305 TI - Genome-wide screen uncovers novel pathways for tRNA processing and nuclear cytoplasmic dynamics. AB - Transfer ribonucleic acids (tRNAs) are essential for protein synthesis. However, key gene products involved in tRNA biogenesis and subcellular movement remain to be discovered. We conducted the first comprehensive unbiased analysis of the role of nearly an entire proteome in tRNA biology and describe 162 novel and 12 previously known Saccharomyces cerevisiae gene products that function in tRNA processing, turnover, and subcellular movement. tRNA nuclear export is of particular interest because it is essential, but the known tRNA exporters (Los1 [exportin-t] and Msn5 [exportin-5]) are unessential. We report that mutations of CRM1 (Exportin-1), MEX67/MTR2 (TAP/p15), and five nucleoporins cause accumulation of unspliced tRNA, a hallmark of defective tRNA nuclear export. CRM1 mutation genetically interacts with los1Delta and causes altered tRNA nuclear-cytoplasmic distribution. The data implicate roles for the protein and mRNA nuclear export machineries in tRNA nuclear export. Mutations of genes encoding actin cytoskeleton components and mitochondrial outer membrane proteins also cause accumulation of unspliced tRNA, likely due to defective splicing on mitochondria. Additional gene products, such as chromatin modification enzymes, have unanticipated effects on pre-tRNA end processing. Thus, this genome-wide screen uncovered putative novel pathways for tRNA nuclear export and extensive links between tRNA biology and other aspects of cell physiology. PMID- 26680309 TI - Preoperative Renal Function Predicts Hospital Costs and Length of Stay in Coronary Artery Bypass Grafting. AB - BACKGROUND: Renal failure remains a major source of morbidity after cardiac surgery. Whereas the relationship between poor renal function and worse cardiac surgical outcomes is well established, the ability to predict the impact of preoperative renal insufficiency on hospital costs and health care resource utilization remains unknown. METHODS: Patient records from a statewide The Society for Thoracic Surgeons (STS) database linked with estimated cost data were evaluated for isolated coronary artery bypass graft (CABG) operations (2000 to 2012). Patients with documented preoperative renal failure/dialysis were excluded. Preoperative renal function was determined using calculated creatinine clearance (CrCl). Multivariable regression analyses utilizing restricted cubic splines evaluated the continuous relationship between CrCl and risk-adjusted outcomes. RESULTS: A total of 46,577 isolated CABG operations were evaluated with a median STS predicted risk of mortality score of 1.2% (interquartile range, 0.7% to 2.4%), including 9% off-pump CABG. Median CrCl was 85 mL/min (range, 2 to 120 mL/min), and median total cost was $25,011. After adjustment for preoperative risk factors, worsening CrCl (declining renal function) was highly associated with greater total costs of hospitalization (coefficient = -122, p < 0.001) and postoperative length of stay (coefficient = -0.03, p < 0.001). Furthermore, predicted total costs were incrementally increased by 10%, 20%, and 30% with worsening of CrCl from 80 mL/min to 60, 40, and 20 mL/min. As expected, decreasing CrCl was also associated with an increased risk-adjusted likelihood for hemodialysis and mortality (both p < 0.001). CONCLUSIONS: Preoperative renal function is highly associated with the cost of CABG. Assessment of renal function may be used to preoperatively predict cost and resource utilization. Optimizing renal function preoperatively has the potential to improve patient quality and costs by approximately 6% ($1,250) for every 10 mL/min improvement in creatinine clearance. PMID- 26680308 TI - Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation? AB - INTRODUCTION: Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. AREAS COVERED: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. EXPERT OPINION: The change of the US FDA pregnancy classification scheme to an evidence based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children. PMID- 26680310 TI - The Society of Thoracic Surgeons Clinical Practice Guidelines on Arterial Conduits for Coronary Artery Bypass Grafting. AB - Internal thoracic arteries (ITAs) should be used to bypass the left anterior descending (LAD) artery when bypass of the LAD is indicated (class of recommendation [COR] I, level of evidence [LOE] B). As an adjunct to left internal thoracic artery (LITA), a second arterial graft (right ITA or radial artery [RA]) should be considered in appropriate patients (COR IIa, LOE B). Use of bilateral ITAs (BITAs) should be considered in patients who do not have an excessive risk of sternal complications (COR IIa, LOE B). To reduce the risk of sternal infection with BITA, skeletonized grafts should be considered (COR IIa, LOE B), smoking cessation is recommended (COR I, LOE C), glycemic control should be considered (COR IIa, LOE B), and enhanced sternal stabilization may be considered (COR IIb, LOE C). As an adjunct to LITA to LAD (or in patients with inadequate LITA grafts), use of a RA graft is reasonable when grafting coronary targets with severe stenoses (COR IIa, LOE: B). When RA grafts are used, it is reasonable to use pharmacologic agents to reduce acute intraoperative and perioperative spasm (COR IIa, LOE C). The right gastroepiploic artery may be considered in patients with poor conduit options or as an adjunct to more complete arterial revascularization (COR IIb, LOE B). Use of arterial grafts (specific targets, number, and type) should be a part of the discussion of the heart team in determining the optimal approach for each patient (COR I, LOE C). PMID- 26680311 TI - Survival in Patients With Esophageal Adenocarcinoma Undergoing Trimodality Therapy Is Independent of Regional Lymph Node Location. AB - BACKGROUND: The American Joint Committee on Cancer Cancer Staging Manual 7th Edition esophageal cancer staging was derived from outcomes of patients undergoing esophagectomy alone and eliminated nodal location from its schema. A limitation of this staging system is that it has not been validated in the setting of multimodality therapy for esophageal cancer. In addition, nodal location continues to influence treatment decisions. The aim of our study was to evaluate outcomes of patients with distal esophageal or gastroesophageal junction (GEJ) adenocarcinoma undergoing trimodality therapy and assess the effect of nodal location on survival. METHODS: This multiinstitutional retrospective study assessed patients with clinically node-positive (cN+) distal esophageal/GEJ adenocarcinoma treated with trimodality therapy between January 2002 and December 2011. Nodal stations were classified as paratracheal, subcarinal, celiac, lower esophageal, paraaortic, supraclavicular, or perigastric/perihepatic. Overall survival (OS) was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify variables associated with OS. RESULTS: A total of 196 cN+ patients met the study criteria. The most prevalent metastatic nodal location was in the perigastric region, present in 141 patients (72%); paratracheal nodal involvement was present in 19 patients (10%). None of the nodal stations was significantly associated with OS on univariable analysis. Multivariable analysis identified age (hazard ratio [HR], 1.036; p = 0.001), male sex (HR, 2.39; p = 0.003), pathologic ypT3 (HR, 1.81; p = 0.048), and ypN3 (HR, 2.93; p = 0.003) as being significantly associated with survival. CONCLUSIONS: The location of cN+ regional node disease in patients with distal esophageal or GEJ adenocarcinoma was not predictive of survival after trimodality therapy. Age, sex, pathologic tumor depth, and the number of involved nodes were independent predictors of survival. Patients with cN+ cancers should not be deprived of potentially curative surgical resection based solely on the location of regional nodal disease. PMID- 26680312 TI - Improved Exercise Performance in Patients With Tricuspid Atresia After the Fontan Bjork Modification With Pulsatile Systolic Pulmonary Flow. AB - BACKGROUND: After the Fontan-Bjork modification for tricuspid atresia, some patients show pulsatile systolic pulmonary flow. We compared the hemodynamic findings and the clinical presentation of patients with and without pulsatile systolic flow after atrioventricular connection. METHODS: According to the pulmonary flow pattern by pulsed-wave Doppler assessment of transthoracic echocardiography, 41 patients after atrioventricular connection were divided into two groups: patients who showed dominant pulsatile systolic pulmonary flow (group P, n = 11), and patients who did not (group N, n = 30). RESULTS: Mean follow-up time was 27.8 +/- 4.7 years in group P and 25.3 +/- 3.8 years in group N (p = 0.1). Patients in group P had significantly less frequently catheter ablation procedures for tachyarrhythmia (9% versus 50%, p = 0.03). No patient in group P had had cardiac decompensation, whereas 7 patients (23%) in group N had had an episode of cardiac decompensation (p = 0.08). Cardiopulmonary exercise testing revealed that patients in group P showed higher oxygen uptake compared with patients in group N (25.0 +/- 7.3 versus 19.6 +/- 6.0 mL . kg(-1) . min(-1), p = 0.03). Patients in group P showed higher systolic pulmonary artery pressure (21.3 +/- 8.4 versus 16.8 +/- 4.5 mm Hg, p = 0.05), higher right ventricular end diastolic volume index (88.6 +/- 30.2 versus 50.3 +/- 28.5 mL . L(-1) . m(-2), p = 0.03), and higher right ventricle to left ventricle ratio of end-diastolic volume index (1.4 +/- 0.6 to 0.7 +/- 0.3, p = 0.01). CONCLUSIONS: Patients with pulsatile systolic flow in the pulmonary artery had better hemodynamic and better exercise performance compared with patients without pulsatile systolic flow after atrioventricular connection. A sufficient volume and function of the right ventricle is a prerequisite to create pulsatile systolic flow. PMID- 26680313 TI - Factors in the Selection and Management of Chest Tubes After Pulmonary Lobectomy: Results of a National Survey of Thoracic Surgeons. AB - BACKGROUND: This study determined patterns of chest tube (CT) selection and management after open lobectomy and minimally invasive lobectomy by thoracic surgeons. METHODS: Surveys were sent electronically to 5,175 thoracic surgeons, and 475 were completed. Responses, blinded so individuals could not be identified, were analyzed and compared according to surgeon characteristics (academic/private practice, years in practice, lobectomy volume, and geographic region). All indicated differences were statistically significant (p < 0.05 by chi(2) tests). RESULTS: CT selection: Most surgeons prefer rigid tubes, and the size most commonly used was 28F. Most place 2 CTs after open lobectomy and 1 CT after minimally invasive lobectomy. Academic surgeons are more likely than private surgeons to use 1 tube after open lobectomy, but both prefer 1 tube after minimally invasive lobectomy. Younger surgeons and high-volume surgeons are more likely to use 1 CT than senior surgeons and low-volume surgeons after both open lobectomy and minimally invasive lobectomy. CT management: Academic and younger surgeons remove the CT sooner after open lobectomy. Younger and high-volume surgeons remove the CT with greater drainage amounts. All groups remove CTs sooner after minimally invasive lobectomy than after open lobectomy. Approximately half of surgeons get a daily chest roentgenogram. Younger and low volume surgeons are most likely to discharge patients with Heimlich valves, although overall use was in less than 5% (49 of 475) of respondents. Most surgeons believe clinical experience rather than training or the literature determined their CT strategy. CONCLUSIONS: This survey determined the difference in CT management among various groups of surgeons. Clinical experience was the most important factor in determining their CT strategy. PMID- 26680315 TI - A bimodal molecular imaging probe based on chitosan encapsulated magneto fluorescent nanocomposite offers biocompatibility, visualization of specific cancer cells in vitro and lung tissues in vivo. AB - Multifunctional hybrid nanocomposite material, consists of chitosan encapsulated iron oxide (as MRI contrasting agent), CdS (as fluorescent probe) nanoparticles and podophyllotoxin (as anticancer drug) was synthesized and characterized. The TEM studies suggested the size of the NPs to be in the range of 80-100 nm. These nanocomposites were treated with different cancer cell lines viz., KB, C6 and A549 cells. Fluorescence imaging and Perl's Prussian blue staining confirmed the presence of these nanocomposites inside both KB and C6 cells but not in A549 cells. Cytotoxicity experiments revealed that these biopolymer coated nanocomposites showed minimal toxicity towards cancerous cells. Further the intraperitoneal administration of one of the nanoformulations to Wistar rats suggested deposition of these nanocomposites in the lungs. The hematological, biochemical and histopathological analysis confirmed that these nanocomposites are safe to use as a novel dual mode imaging material. PMID- 26680314 TI - Five Years of Experimental Warming Increases the Biodiversity and Productivity of Phytoplankton. AB - Phytoplankton are key components of aquatic ecosystems, fixing CO2 from the atmosphere through photosynthesis and supporting secondary production, yet relatively little is known about how future global warming might alter their biodiversity and associated ecosystem functioning. Here, we explore how the structure, function, and biodiversity of a planktonic metacommunity was altered after five years of experimental warming. Our outdoor mesocosm experiment was open to natural dispersal from the regional species pool, allowing us to explore the effects of experimental warming in the context of metacommunity dynamics. Warming of 4 degrees C led to a 67% increase in the species richness of the phytoplankton, more evenly-distributed abundance, and higher rates of gross primary productivity. Warming elevated productivity indirectly, by increasing the biodiversity and biomass of the local phytoplankton communities. Warming also systematically shifted the taxonomic and functional trait composition of the phytoplankton, favoring large, colonial, inedible phytoplankton taxa, suggesting stronger top-down control, mediated by zooplankton grazing played an important role. Overall, our findings suggest that temperature can modulate species coexistence, and through such mechanisms, global warming could, in some cases, increase the species richness and productivity of phytoplankton communities. PMID- 26680316 TI - Formulation of 20(S)-protopanaxadiol nanocrystals to improve oral bioavailability and brain delivery. AB - The aim of this study was to fabricate 20(S)-protopanaxadiol (PPD) nanocrystals to improve PPD's oral bioavailability and brain delivery. PPD nanocrystals were fabricated using an anti-solvent precipitation approach where d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was optimized as the stabilizer. The fabricated nanocrystals were nearly spherical with a particle size and drug loading of 90.44 +/- 1.45 nm and 76.92%, respectively. They are in the crystalline state and stable at 4 degrees C for at least 1 month. More than 90% of the PPD could be rapidly released from the nanocrystals, which was much faster than the physical mixture and PPD powder. PPD nanocrystals demonstrated comparable permeability to solution at 2.52 +/- 0.44*10(-5)cm/s on MDCK monolayers. After oral administration of PPD nanocrystals to rats, PPD was absorbed quickly into the plasma and brain with significantly higher Cmax and AUC0-t compared to those of the physical mixture. However, no brain targeting was observed, as the ratios of the plasma AUC0-t to brain AUC0-t for the two groups were similar. In summary, PPD nanocrystals are a potential oral delivery system to improve PPD's poor bioavailability and its delivery into the brain for neurodegenerative disease and intracranial tumor therapies in the future. PMID- 26680317 TI - TKD peptide as a ligand targeting drug delivery systems to memHsp70-positive breast cancer. AB - Breast cancer has been considered as a serious threat to females' life. Active targeting drug delivery is a potential strategy in cancer therapy, which however is hindered by the targeting efficiency. Herein, a 14-mer peptide (TKD) derived from the oligomerization domain of membrane heat-shock protein 70 (memHsp70), for the first time, was exploited as a tumor-targeting ligand to modify polymeric micelles. NMR results demonstrated the successful synthesis of TKD-PEG-PLGA polymer. No difference was observed in the drug release between TKD-modified doxorubicin (DOX)-loaded micelles (TKD-D-M) and unmodified counterparts. The modification of TKD mediated apparently higher cellular uptake within memHsp70 positive MCF-7 cells, compared to normal MCF-10A cells. Excessive TKD pretreatment significantly inhibited the cellular uptake of TKD-D-M, indicating the receptor-mediated mechanism. Enhanced accumulation of TKD-D-M within the tumor of MCF-7 bearing mice further demonstrated the targeting ability of TKD in vivo. CCK-8 assay showed that the modification of TKD significantly increase the anti-proliferation effect against MCF-7 cells. The findings demonstrated that TKD peptide is a potential ligand which can target drug delivery systems to memHsp70 positive breast cancer. PMID- 26680318 TI - Influence of surfactants in self-microemulsifying formulations on enhancing oral bioavailability of oxyresveratrol: Studies in Caco-2 cells and in vivo. AB - Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 and Labrasol) and two levels (low; 5% and high; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH 1.2. After dilution with different media, the microemulsion droplet sizes of the Tween80-based (~26 to 36 nm) were smaller than that of the Labrasol-based systems (~34 to 45 nm). Both systems with high levels of surfactant increased the Caco-2 cells permeability of OXY compared to those with low levels of surfactant (1.4-1.7 folds) and the unformulated OXY (1.9-2.0 folds). It was of interest, that there was a reduction (4.4-5.3 folds) in the efflux transport of OXY from both systems compared to the unformulated OXY. The results were in good agreement with the in vivo absorption studies of such OXY-formulations in rats. Significantly greater values of Cmax and AUC(0-10h) (p<0.05) were obtained from the high levels of Tween80-based (F(r,0-10h) 786.32%) compared to those from the Labrasol-based system (F(r,0-10h) 218.32%). These finding indicate the importance of formulation variables such as type and quantity of surfactant in the SMEDDS to enhance oral drug bioavailability. PMID- 26680319 TI - Standardising HbA1c-based diabetes diagnosis: opportunities and challenges. AB - Globally, the incidence of diabetes mellitus is rising at an alarming rate and has become a health crisis that threatens the economies of all nations. Therefore, diagnosing diabetes has become an important issue in the management of diabetes. Glycated hemoglobin (HbA1c) is now recommended as a means to diagnose diabetes, but its use still has limitations. In this article, the biology, measurement, standardization, and opportunities and challenges of the use of HbA1c to diagnose diabetes are reviewed. More specifically, its use in China and the Asian region is discussed in detail. PMID- 26680320 TI - A new association for the oral metagenome. PMID- 26680321 TI - Development of a sensitive enzyme-linked immunosorbent assay for the measurement of biologically active etanercept in patients with ankylosing spondylitis. AB - Etanercept is the first tumor necrosis factor inhibitor to be approved for rheumatic disease treatment. Its in vivo concentration is usually detected with commercial enzyme-linked immunosorbent assay (ELISA) kits; specifically, previous researchers have mostly used double-antibody sandwich ELISA technology. Double antibody sandwich ELISA is employed to detect the total etanercept rather than biologically active etanercept, which is more relevant in terms of therapeutic drug monitoring. In this work, a sensitive ELISA that employed its antigen TNF alpha to capture biologically active etanercept for concentration detection was established and validated for etanercept pharmacokinetic (PK) study in patients with ankylosing spondylitis (AS). The proposed assay was demonstrated to be precise and accurate over the linear range of 12.5-400pg/mL. The intra- and inter assay relative standard deviation ranged from 3.9 to 12.2% and 6.2 to 11.1%, respectively, and recovery varied between 90.1 and 99.7%, confirming the assay's reliability. The effectiveness and accuracy of the assay was also validated according to quality samples containing etanercept with different TNF-alpha concentrations, and with plasma samples from patients with AS. To complete the study, both the proposed assay and double-antibody sandwich ELISA were applied to the PK study of etanercept in patients and compared. The multiple-dose results of both analytical methods were consistent, while the drug exposure of the first dose as-detected by the proposed assay was lower than that detected by double antibody sandwich ELISA. In conclusion, the proposed ELISA was shown to provide more accurate concentration data for therapeutic drug monitoring in comparison to commercial ELISA kits. PMID- 26680322 TI - Water-compatible molecularly imprinted polymers for selective solid phase extraction of dencichine from the aqueous extract of Panax notoginseng. AB - Specific molecularly imprinted polymers for dencichine were developed for the first time in this study by the bulk polymerization using phenylpyruvic acid and dl-tyrosine as multi-templates. The photographs confirmed that molecularly imprinted polymers prepared using N,N'-methylene diacrylamide as cross-linker and glycol dimethyl ether as porogen displayed excellent hydrophilicity. Selectivity, adsorption isotherm and adsorption kinetics were investigated. The sample loading washing-eluting solvent was optimized to evaluate the property of molecularly imprinted solid phase extract. Compared with LC/WCX-SPE, water-compatible molecularly imprinted solid phase extraction displayed more excellent specific adsorption performance. The extracted dencichine from Panax notoginseng with the purity of 98.5% and the average recovery of 85.6% (n=3) was obtained. PMID- 26680323 TI - Highly specific phosphopeptide enrichment by titanium(IV) cross-linked chitosan composite. AB - Natural chitosan was applied as supporting material for Ti(IV) based immobilized metal ion affinity chromatographic (IMAC) material (Ti-CTS). Compared with other polymer based IMAC, Ti-CTS can save the cockamamie synthesis procedures and be easy to obtain. The morphology, surface area, pore volume and elemental composition of Ti-CTS were revealed by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) method and X-ray photoelectron spectroscopy (XPS). Tryptic digest products from several standard proteins and two real samples (non fat milk and serum) were enriched using Ti-CTS to demonstrate the efficiency of this method. The results showed that this composite enables high sensitive and selective phosphopeptide enrichment from casein variants, non-fat milk and human serum. Furthermore, multi-phosphorylated peptides with three serine phospholated sites (S*S*S*) demonstrated high affinity to Ti-CTS. Hence, this method had great potential for future studies of complex phosphoproteomes and especially multi phosphorylated peptides. PMID- 26680324 TI - Influence of buffer concentration on electrospray ionisation of gamma hydroxybutyrate adducts with the components of the mobile phase used in liquid chromatography-tandem mass spectrometry. PMID- 26680325 TI - Quantitative analysis of pasireotide (SOM230), a cyclic peptide, in monkey plasma using liquid chromatography in combination with tandem mass spectrometry. AB - A novel liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the determination of Pasireotide (SOM230) was developed and validated with a dynamic range of 0.5-250ng/ml using 50MUl of monkey plasma. SOM230 and the internal standard, [M+6]SOM230, were extracted from monkey plasma via MUElution SPE. The acidified sample matrix was loaded onto the preconditioned Waters SPE plate for further processing. The analyte was eluted from the SPE plate using freshly prepared elution solvent, which was followed by dilution and LC-MS/MS analysis. By eliminating a step of evaporation of the SPE eluent, instead, injecting the eluent after a simple dilution, compound loss due to non specific binding to the 96-well materials was prevented. Furthermore, freshly prepared elution solution was found a key to optimal extraction recovery of the analyte from monkey plasma. The optimal chromatographic separation was achieved on an Atlantis dC18 (50*2.1mm, 5MUm particle size) column using gradient elution with a total analysis cycle time approximately 4min per injection. The mobile phases were water containing 0.5% acetic acid and 0.05% trifluoroacetic acid (TFA) (mobile phase A) and acetonitrile containing 0.5% acetic acid and 0.05% TFA (mobile phase B). The incorporation of TFA (0.05%, v/v) and acetic acid (0.5%, v/v) into the mobile phases was accompanied by the improved chromatography and minimized carryover due to the HPLC column. The current method was validated for specificity, sensitivity, matrix effect, recovery, linearity, accuracy and precision, dilution integrity, batch size and stability. The accuracy and precision for the LLOQs (0.5ng/ml) were within +/-5.6% bias and <=7.8% CV, respectively. From the intra-day and inter-day evaluations, the precision of the other QC samples (1.5, 7.5, 75 and 190ng/ml) ranged from 2.7 to 4.9% CV and the accuracy (% bias) from -1.3 to 7.3%, respectively. Additional assessment of incurred sample reanalysis (ISR) was conducted to demonstrate the ruggedness and robustness of the assay method. The validated method was successfully implemented to support a toxicity study in monkeys administered with 5 and 30mg of SOM230 in a single intramuscular injection of a long acting release (LAR) formulation. PMID- 26680326 TI - Study on pharmacokinetics of 3,4-divanillyltetrahydrofuran in rats by ultra-fast liquid chromatography/tandem mass spectrometry. AB - 3,4-Divanillyltetrahydrofuran is the main active ingredient of nettle root which can increase steroid hormones in the bloodstream for many of bodybuilders. To better understand its pharmacological activities, we need to determine its pharmacokinetic profiles. In this study, a rapid and sensitive ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the determination of 3,4-divanillyltetrahydrofuran in the plasma of rats. Chromatographic separation was performed on a C18 column at 40 degrees C, with a gradient elution consisting of methanol and water containing 0.3% (v/v) formic acid at a flow rate of 0.8mL/min. The detection was performed using an electrospray triple-quadrupole MS/MS via positive ion multiple reaction monitoring mode. The lower limits-of-quantification determined were 0.5ng/mL. The intra- and inter-day precision (RSD%) was found to be within 15% and the accuracy (RE%) ranged from -4.0% to 7.0%. This simple yet sensitive method was fully validated and could be successfully applied to the study on pharmacokinetics of 3, 4-divanillyltetrahydrofuran. PMID- 26680327 TI - New regulation for clinical stem cell research in China: expected impact and challenges for implementation. PMID- 26680328 TI - Small is Smarter: Nano MRI Contrast Agents - Advantages and Recent Achievements. AB - Many challenges for advanced sensitive and noninvasive clinical diagnostic imaging remain unmatched. In particular, the great potential of magnetic nano probes is intensively discussed to further improve the performance of magnetic resonance imaging (MRI), especially for cancer diagnosis. Based on recent achievements, here the concepts of magnetic nanoparticle-based MRI contrast agents and tumor-specific imaging probes are critically summarized. Advances in their synthesis, biocompatible chemical and biofunctional surface modifications, and current strategies for further developing them into multimodality imaging probes are discussed. In addition, how engineered versus unintended surface coatings such as protein coronas affect the biocompatibility and performance of MRI nano-probes is also considered. To stimulate progress in the field, future strategies and relevant challenges that still need to be resolved in the field conclude this review. PMID- 26680339 TI - Burnout and Engagement as Mediators in the Relationship between Work Characteristics and Turnover Intentions across Two Ibero-American Nations. AB - This study examines the mediating effects of burnout and engagement on the relationships between work characteristics (work overload and social support) and turnover intentions in the nursing community of two Ibero-American countries within the job demands-resources model. The sample consists of 316 registered nurses employed in Uruguay and 502 employed in Spain. We used multiple structural equation modelling analyses. The proposed model fit the data for both nursing samples. Burnout was found to fully mediate the relationship between work overload and turnover intention, whereas work engagement partially mediates the relationship between social support and turnover intention. The results contribute to our understanding of the potential applicability of two leading empirical models and of the dynamic relationship between work characteristics and turnover intentions through work engagement and burnout. Researchers should continue to focus on gaining a broader understanding of the effects of work characteristics in healthcare facilities and the associated organizational outcomes. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26680338 TI - The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis. AB - BACKGROUND: Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse. OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions. RESULTS: Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety. CONCLUSIONS: Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD. PMID- 26680340 TI - England's current GP inspection system misses crucial patient safety warnings, MPs hear. PMID- 26680341 TI - Influence of Glycosylation Inhibition on the Binding of KIR3DL1 to HLA-B*57:01. AB - Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I N-glycan has on KIR:HLA interactions and NK cell function. We focused on HLA-B*57:01 and its interaction with KIR3DL1, which has been shown to play a critical role in determining the progression of a number of human diseases, including human immunodeficiency virus-1 infection. 721.221 cells stably expressing HLA-B*57:01 were treated with a panel of glycosylation enzyme inhibitors, and HLA class I expression and KIR3DL1 binding was quantified. In addition, the functional outcomes of HLA-B*57:01 N-glycan disruption/modulation on KIR3DL1zeta+ Jurkat reporter cells and primary human KIR3DL1+ NK cells was assessed. Different glycosylation enzyme inhibitors had varying effects on HLA B*57:01 expression and KIR3DL1-Fc binding. The most remarkable effect was that of tunicamycin, an inhibitor of the first step of N-glycosylation, which resulted in significantly reduced KIR3DL1-Fc binding despite sustained expression of HLA B*57:01 on 721.221 cells. This effect was paralleled by decreased activation of KIR3DL1zeta+ Jurkat reporter cells, as well as increased degranulation of primary human KIR3DL1+ NK cell clones when encountering HLA-B*57:01-expressing 721.221 cells that were pre-treated with tunicamycin. Overall, these results demonstrate that N-glycosylation of HLA class I is important for KIR:HLA binding and has an impact on NK cell function. PMID- 26680343 TI - Single coronary artery anomaly: Report of an extremely rare variation. AB - A 43-year-old man presented with unstable angina. Coronary angiography revealed a single coronary artery originating from the left sinus of Valsalva, giving rise to a left main stem trifurcating to the left anterior descending artery, left circumflex artery, and an anomalous right coronary artery. The anomalous right coronary artery had a retroaortic course and significant proximal tubular stenosis which was stented. The coronary anomaly and abnormal course was confirmed by transesophageal echocardiography. The patient was symptom-free at one-year follow-up. This anomaly does not predispose to accelerated atherosclerosis, and the premature atherosclerosis in our patient was probably due an unhealthy lifestyle. PMID- 26680342 TI - The ad-libitum alcohol 'taste test': secondary analyses of potential confounds and construct validity. AB - RATIONALE: Motivation to drink alcohol can be measured in the laboratory using an ad-libitum 'taste test', in which participants rate the taste of alcoholic drinks whilst their intake is covertly monitored. Little is known about the construct validity of this paradigm. OBJECTIVE: The objective of this study was to investigate variables that may compromise the validity of this paradigm and its construct validity. METHODS: We re-analysed data from 12 studies from our laboratory that incorporated an ad-libitum taste test. We considered time of day and participants' awareness of the purpose of the taste test as potential confounding variables. We examined whether gender, typical alcohol consumption, subjective craving, scores on the Alcohol Use Disorders Identification Test and perceived pleasantness of the drinks predicted ad-libitum consumption (construct validity). RESULTS: We included 762 participants (462 female). Participant awareness and time of day were not related to ad-libitum alcohol consumption. Males drank significantly more alcohol than females (p < 0.001), and individual differences in typical alcohol consumption (p = 0.04), craving (p < 0.001) and perceived pleasantness of the drinks (p = 0.04) were all significant predictors of ad-libitum consumption. CONCLUSIONS: We found little evidence that time of day or participant awareness influenced alcohol consumption. The construct validity of the taste test was supported by relationships between ad-libitum consumption and typical alcohol consumption, craving and pleasantness ratings of the drinks. The ad-libitum taste test is a valid method for the assessment of alcohol intake in the laboratory. PMID- 26680344 TI - Clinical and histopathologic analysis of 46 cases of cutaneous adverse reactions to imatinib. AB - BACKGROUND: Although many cases of cutaneous adverse reactions to imatinib have been reported, their clinical and histopathologic characteristics are not well documented. OBJECTIVES: The present study investigated clinical and histopathologic characteristics of cutaneous adverse reactions to imatinib. METHODS: This retrospective study referred to 46 patients who experienced cutaneous adverse reactions to imatinib. Clinical data including age, sex, skin lesion morphology, underlying disorders, and imatinib treatment parameters (duration of imatinib medication, initial dose, and treatment modifications at the time of the study) were collected. Histopathologic data were available for all patients. RESULTS: Cutaneous adverse reactions to imatinib developed at 1-24 weeks (median onset: 8 weeks) after imatinib administration. The severity of the reaction was categorized as grade 1 in 22%, grade 2 in 41%, and grade 3 in 37% of patients. Onset was earlier in high-severity reactions than in low-severity reactions. The severity of the reaction was dependent on imatinib dose. Grade 3 reactions were noted in nine of 16 (56%) patients administered "high-dose" (600 mg/d) imatinib. Spongiosis (78% of patients) and papillary dermal edema (83% of patients) were common histopathologic findings in the epidermis and dermis, respectively. Lymphohistiocytes were more predominant than eosinophils in dermal inflammatory infiltration. Histopathologic findings did not differ according to dose of imatinib or severity of the reaction. CONCLUSIONS: Although the clinical features of cutaneous adverse reactions to imatinib depend on imatinib dose and the severity of the reaction, histopathologic findings are not associated with these clinical variables. PMID- 26680345 TI - Distribution and Characterisation of Goblet Cells in the Large Intestine of Ostriches during the Pre- and Post-Hatch Period. AB - The role of goblet cell secretion, containing mucopolysaccharides, in the formation of a protective barrier of intestinal mucosa and transportation of the intestinal content has been described quite extensively. However, information on the quality composition of mucopolysaccharides and its changes in the intestinal tract of ostrich chicks, especially in the large intestinal segments, is unavailable. In the current study, ostrich embryos/chicks (n = 6/36) of both sexes were used shortly before hatching and during the first months of the post hatch period. Tissues for histology were taken from the large intestine: the medium segments of the caecum, proximal and distal parts of colon. By using histochemical reactions, the differentiation of goblet cells as well as chemical composition of mucopolysaccharides was carried out. The cells contained acid (AB+), neutral (PAS+) and mixed (AB/PAS+) mucopolysaccharides. The number of goblet cells in the large intestine per unit area of mucosa increased towards the cloaca, and it was the highest in the distal part of the colon. The qualitative goblet cell composition in different large intestinal parts was different in all ages. In the caecum, goblet cells containing acid and mixed mucopolysaccharides dominate post-hatch, whereas in the colon, goblet cells containing acid mucopolysaccharides predominated. The most rapid changes in the qualitative goblet cell composition occur during the first week post-hatch when in all the intestinal segments the proportion of cells containing acid mucopolysaccharides continuously increased. PMID- 26680361 TI - Regulating effect of beta-ketoacyl synthase domain of fatty acid synthase on fatty acyl chain length in de novo fatty acid synthesis. AB - Fatty acid synthase (FAS) is a multifunctional homodimeric protein, and is the key enzyme required for the anabolic conversion of dietary carbohydrates to fatty acids. FAS synthesizes long-chain fatty acids from three substrates: acetyl-CoA as a primer, malonyl-CoA as a 2 carbon donor, and NADPH for reduction. The entire reaction is composed of numerous sequential steps, each catalyzed by a specific functional domain of the enzyme. FAS comprises seven different functional domains, among which the beta-ketoacyl synthase (KS) domain carries out the key condensation reaction to elongate the length of fatty acid chain. Acyl tail length controlled fatty acid synthesis in eukaryotes is a classic example of how a chain building multienzyme works. Different hypotheses have been put forward to explain how those sub-units of FAS are orchestrated to produce fatty acids with proper molecular weight. In the present study, molecular dynamic simulation based binding free energy calculation and access tunnels analysis showed that the C16 acyl tail fatty acid, the major product of FAS, fits to the active site on KS domain better than any other substrates. These simulations supported a new hypothesis about the mechanism of fatty acid production ratio: the geometric shape of active site on KS domain might play a determinate role. PMID- 26680360 TI - A Novel Anti-Inflammatory Effect for High Density Lipoprotein. AB - High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID- 26680362 TI - Improvement of mTORC1-driven overproduction of apoB-containing triacylglyceride rich lipoproteins by short-chain fatty acids, 4-phenylbutyric acid and (R)-alpha lipoic acid, in human hepatocellular carcinoma cells. AB - The activation of hepatic kinase mechanistic target of rapamycin complex 1 (mTORC1) is implicated in the development of obesity-related metabolic disorders. This study investigated the metabolic sequelae of mTORC1 hyperactivation in human hepatoma cells and the lipid-regulating mechanisms of two short-chain fatty acids: 4-phenylbutyric acid (PBA) and (R)-alpha-lipoic acid (LA). We created three stable cell lines that exhibit low, normal, or high mTORC1 activity. mTORC1 hyperactivation induced the expression of lipogenic (DGAT1 and DGAT2) and lipoprotein assembly (MTP and APOB) genes, thereby raising cellular triacylglyceride (TG) and exacerbating secretion of apoB-containing TG-rich lipoproteins. LYS6K2, a specific inhibitor of the p70 S6 kinase branch of mTORC1 signaling, reversed these effects. PBA and LA decreased secreted TG through distinct mechanisms. PBA repressed apoB expression (both mRNA and protein) and lowered secreted TG without mitigation of mTORC1 hyperactivity or activation of AMPK. LA decreased cellular and secreted TG by attenuating mTORC1 signaling in an AMPK-independent manner. LA did not regulate apoB expression but led to the secretion of apoB-containing TG-poor lipoproteins by repressing the expression of lipogenic genes, FASN, DGAT1, and DGAT2. Our studies provide new mechanistic insight into the hypolipidemic activity of PBA and LA in the context of mTORC1 hyperactivation and suggest that the short-chain fatty acids may aid in the prevention and treatment of hypertriglyceridemia. PMID- 26680363 TI - Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression. AB - Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena(INV) isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena(INV) within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena(INV) isoform-specific monoclonal antibody and used it to examine Mena(INV) expression patterns in mouse mammary and human breast tumors. Mena(INV) expression increases during tumor progression and to examine the relationship between Mena(INV) expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena(INV) robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena(INV)-isoform specific antibody, and provide the first description of endogenous Mena(INV) protein expression in mouse and human tumors. PMID- 26680364 TI - Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-diarylazetidin-2-ones as Tubulin-Targeting Antitumor Agents. AB - Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2 ones were investigated, leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3 phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4 methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl "A" ring and 4-phenyl "B" ring for potent antiproliferative activity and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC50 values of 38 and 19 nM, respectively, in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular structure in MCF-7 cells as visualized by confocal microscopy, and caused G2/M arrest and apoptosis. Compound 90b possessed a mean GI50 value of 22 nM in the NCI60 cell line screen, displayed minimal cytotoxicity, and was shown to interact at the colchicine-binding site on beta-tubulin. Phosphate and amino acid prodrugs of both 78b and 90b were synthesized, of which the alanine amide 102b retained potency and is a promising candidate for further clinical development. PMID- 26680365 TI - [Clinical remission in rheumatoid arthritis. Data from the early arthritis cohort study CAPEA]. AB - OBJECTIVE: To evaluate remission rates and therapeutic strategies in the routine care of early rheumatoid arthritis. METHODS: Between 2010 and 2013, a total of 1,301 patients with early arthritis were followed by 89 rheumatologists for up to 2 years in an early arthritis cohort (CAPEA). Complete 2-year data are available for 669 patients with rheumatoid arthritis. RESULTS: Ninety-three percent of patients were diagnosed with a moderate or high disease activity score (DAS28 > 3.2). Within 6 months, 40 % were in clinical remission (DAS28 < 2.6) and 21 % reached a low disease activity score (DAS28 > 2.6 to < 3.2). This proportion did not substantially increase during the 2-year follow-up. Methotrexate was the standard first-line treatment in 82 % of patients. During follow-up, 10 % were treated with a combination of disease-modifying antirheumatic drugs (DMARDs) and 12 % with biological agents. In 60 % of the patients who did not reach remission within 3 months (and 54 % of patients without remission by 6 months), treatment was not changed. At the beginning, 77 % of patients were treated with glucocorticoids at different starting doses (26 % < 7.5 mg, 29 % 7.5-20 mg, and 45 % >= 20 mg of prednisolone per day). After 2 years, 47 % remained on glucocorticoids. CONCLUSION: While 40 % of patients achieved clinical remission through standard care within 6 months, disease activity remained moderate to high in 37 % of patients at 2 years. In these patients a more consistent application of treatment may have increased the response rates. PMID- 26680366 TI - Expression of Toll-like receptors 3 and 9 in Egyptian systemic lupus erythematosus patients. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a common complex disease characterized by chronic generalized inflammation which may involve several tissues and organs. OBJECTIVE: The aim of this work was to study the expression of Toll-like receptors (TLR) 3 and 9 in SLE patients, and to investigate their relationship to clinical features, disease activity, and damage. PATIENTS AND METHODS: The current study included 24 Egyptian female SLE patients and 15 matched controls. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and damage using the Systemic Lupus International Collaborating Clinics (SLICC) index. Expression of TLR3 and TLR9 in B- (CD19-positive) and T lymphocytes (CD3-positive) was studied using flow cytometry. RESULTS: Patient age ranged between 17 and 42 years (mean 26.17 +/- 5.78 years). There was a significant difference between patients and controls regarding TLR3/CD3, TLR3/CD19, TLR9/CD3, and TLR9/CD19 expression (p < 0.0001). There were significant correlations of TLR3/CD3, TLR3/CD19, and TLR9/CD19 with serum creatinine (r = 0.52, p = 0.009; r = 0.504, p = 0.012; and r = 0.58, p = 0.003; respectively) and negative correlations with ALT levels (r = -0.42, p = 0.04; r = -0.49, p = 0.016; and r = -0.472, p = 0.02; respectively). CONCLUSION: The results of the study suggest that TLR3 and TLR9 play a role in the pathogenesis of SLE, and have an impact on organ involvement in this disease. More studies concerning the biology and function of TLRs are required in larger patient cohorts, and may lead to development of a new class of drugs. PMID- 26680367 TI - [Do we still need clinical studies in rheumatology?]. AB - Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided. PMID- 26680368 TI - A solution to the negative effects of splenectomy during colorectal trauma and surgery: an experimental study on splenic autotransplantation to the groin area. AB - BACKGROUND: Splenectomy after combined colosplenic trauma or iatrogenic splenic injury during colorectal surgery associates with worse short- and long-term outcomes, including reduced survival in patients with colorectal cancer. Splenic autotransplantation may improve the outcomes of such patients. Omental splenic transplantation is the standard procedure but may be difficult when performing laparoscopic colorectal surgery or when total or subtotal omentectomy is required. This animal model study was performed to evaluate the impact of splenic autotransplantation to the groin area on colonic wound healing. METHODS: Thirty rats were divided into three groups of ten animals. One group underwent colon anastomosis and sham splenectomy, the second underwent colon anastomosis and splenectomy, and the third underwent colon anastomosis, splenectomy, and intramuscular autotransplantation of the spleen. On postoperative day 7, anastomotic healing was evaluated by measuring bursting pressure and hydroxyproline levels. The third group was subjected to scintigraphy before sacrifice to assess whether the transplant was functional. RESULTS: The mortality rates of the sham, splenectomized, and transplanted animals were 0 %, 30 %, and 20 %, respectively: the splenectomized animals had significantly lower mean bursting pressures than the other two groups (p = 0.002). The mean hydroxyproline levels of the three groups were 467.4, 335.3, and 412.7 mg hydroxyproline/g protein, respectively (p = 0.0856). Nine of the ten transplanted animals (90 %) had splenic activity on scintigraphy. CONCLUSIONS: Splenectomy impaired the healing of the colonic anastomosis. This effect was largely reversed by splenic autotransplantation. Intramuscular autotransplantation to the groin area appears to be feasible and effective. PMID- 26680369 TI - Recurrent ganglioglioma in adults treated with BRAF inhibitors. AB - Thirteen adult patients with temozolomide, surgery and radiation refractory ganglioglioma were screened for the BRAF V600E mutation. Three (23%) were found positive for the presence of the BRAF mutation and were treated with the BRAF inhibitor dabrafenib. Dabrafenib was well tolerated with no grade 3 or higher toxicity. The median number of cycles was 7 (a cycle was defined as 1 month of daily dabrafenib) and best response was stable disease in two patients and a partial response in one patient. Median progression-free survival was 7 months with a range of 4-10 months. PMID- 26680370 TI - A new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H) ones via sulfonyl radical-triggered addition/6-exo-dig cyclization. AB - A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered alpha,beta conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C-S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity. PMID- 26680371 TI - Ruthenium-Containing Block Copolymer Assemblies: Red-Light-Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy. AB - The use of self-assembled nanostructures consisting of red-light-responsive Ru(II)-containing block copolymers (BCPs) for anticancer phototherapy is demonstrated. Three Ru-containing BCPs with different molecular weights are synthesized. Each BCP contains a hydrophilic poly(ethylene glycol) block and an Ru-containing block. In the Ru-containing block, more than half of the side chains are coordinated with [Ru(2,2':6',2''-terpyridine)(2,2'-biquinoline)](2+) , resulting in more than 40 wt% Ru complex in the BCPs. The Ru complex acts as both a red-light-cleavable moiety and a photoactivated prodrug. Depending on their molecular weights, the BCPs assemble into micelles, vesicles, and large compound micelles. All of the BCP assemblies are taken up by cancer cells. Red-light irradiation releases the Ru complex and generates singlet oxygen ((1) O2 ) in cancer cells. The released Ru complex and (1) O2 inhibit the growth of cancer cells. Among the three BCP assemblies, the BCP micelle exhibits the most efficient cellular uptake and best anticancer performance. PMID- 26680374 TI - Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial. AB - BACKGROUND: The enzyme heme oxygenase-1 (HO-1) degrades heme and protects against ischemia-reperfusion injury. Monocytes/macrophages are the major source of HO-1 and higher levels improve renal transplant outcomes. Heme arginate (HA) safely induces HO-1 in humans. METHODS: The Heme Oxygenase-1 in renal Transplantation study was a randomized, placebo-controlled, IIb trial to evaluate HA effect on HO 1 upregulation after deceased donor kidney transplantation. 40 recipients were randomized to either 3 mg kg HA or placebo (0.9% NaCl), given preoperatively (day 0) and again on day 2. Recipient blood and urine were collected daily. Graft biopsies were taken preoperatively and on day 5. Primary outcome was HO-1 upregulation in peripheral blood mononuclear cells (PBMCs). Secondary outcomes were graft HO-1 upregulation and injury, urinary biomarkers, and renal function. RESULTS: The HA upregulated PBMC HO-1 protein more than placebo at 24 hours: HA 11.1 ng/mL versus placebo 0.14 ng/mL (P = < 0.0001). The PBMC HO-1 messenger RNA also increased: HA 2.73-fold versus placebo 1.41-fold (P = 0.02). Heme arginate increased day 5 tissue HO-1 protein immunopositivity compared with placebo: HA 0.21 versus placebo -0.03 (P = 0.02) and % HO-1-positive renal macrophage also increased: HA 50.8 cells per high power field versus placebo 22.3 (P = 0.012). Urinary biomarkers were reduced after HA but not significantly. Histological injury and renal function were similar but the study was not powered for this. Adverse events were equivalent between groups. CONCLUSIONS: The primary outcome was achieved and demonstrated for the first time that HA safely induces HO-1 in transplant recipients. Planned larger studies will determine the impact of HO-1 upregulation on clinical outcomes and evaluate the benefit to patients at risk of ischemia-reperfusion injury. PMID- 26680373 TI - Eomesodermin(lo) CTLA4(hi) Alloreactive CD8+ Memory T Cells Are Associated With Prolonged Renal Transplant Survival Induced by Regulatory Dendritic Cell Infusion in CTLA4 Immunoglobulin-Treated Nonhuman Primates. AB - BACKGROUND: Memory T cells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to transplant tolerance. The transcription factor Eomesodermin (Eomes) is critical for Tmem development and maintenance, but its expression by alloactivated T cells has not been examined in nonhuman primates. METHODS: We evaluated Eomes and coinhibitory cytotoxic T lymphocyte antigen-4 (CTLA4) expression by alloactivated rhesus monkey T cells in the presence of CTLA4 immunoglobulin, both in vitro and in renal allograft recipients treated with CTLA4Ig, with or without regulatory dendritic cell (DCreg) infusion. RESULTS: In normal monkeys, CD8+ T cells expressed significantly more Eomes than CD4+ T cells. By contrast, CD8+ T cells displayed minimal CTLA4. Among T cell subsets, central Tmem (Tcm) expressed the highest levels of Eomes. Notably, Eomes(lo)CTLA4(hi) cells displayed higher levels of CD25 and Foxp3 than Eomes(hi)CTLA4(lo) CD8+ T cells. After allostimulation, distinct proliferating Eomes(lo)CTLA4(hi) and Eomes(hi)CTLA4(lo) CD8+ T cell populations were identified, with a high proportion of Tcm being Eomes(lo)CTLA4(hi). CB with CTLA4Ig during allostimulation of CD8+ T cells reduced CTLA4 but not Eomes expression, significantly reducing Eomes(lo)CTLA4(hi) cells. After transplantation with CB and rapamycin, donor-reactive Eomes(lo)CTLA4(hi) CD8+ T cells were reduced. However, in monkeys also given DCreg, absolute numbers of these cells were elevated significantly. CONCLUSIONS: Low Eomes and high CTLA4 expression by donor-reactive CD8+ Tmem is associated with prolonged renal allograft survival induced by DCreg infusion in CTLA4Ig-treated monkeys. Prolonged allograft survival associated with DCreg infusion may be related to maintenance of donor-reactive Eomes(lo)CTLA4(hi) Tcm. PMID- 26680376 TI - "Big Operations Using Mini Instruments": The Evolution of Mini Laparoscopy in the Surgical Realm. AB - Laparoscopy using miniature (2-3.5 mm) instruments was introduced in the late 1980s and early 1990s. Though mini laparoscopy (Mini) created new opportunities for surgical diagnosis and therapy, the limitations of early instruments inhibited widespread adoption. This is no longer the case. Mini is enjoying a renaissance, due to several factors: the maturation of minimally invasive surgery (MIS), the failure of laparoendoscopic single-site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES) platforms to achieve early expectations, and the recent significant improvements in Mini instrument functionality and durability. As a result, Mini is being increasingly applied to pediatric and adult procedures across specialties. To assess the current status of Mini laparoscopy, the Society of Laparoendoscopic Surgeons (SLS) and the Florida Hospital Nicholson Center convened an international symposium in February 2015. This report shares highlights from that symposium, "Big Operations Using Mini Instruments." PMID- 26680372 TI - The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients. AB - Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID- 26680375 TI - Plasma IL-10 Levels to Guide Antiviral Prophylaxis Prevention of Late-Onset Cytomegalovirus Disease, in High Risk Solid Kidney and Liver Transplant Recipients. AB - BACKGROUND: Immune measurements that distinguish solid organ transplantation (SOT) recipients who control cytomegalovirus (CMV) infection from those who progress to CMV-disease (CMV-dz) may be clinically useful in guiding tailored prevention strategies. We previously reported that elevated plasma levels of the immune-modulator IL-10 are associated with late CMV-dz. Here we evaluate whether IL-10 levels measured soon after prophylaxis discontinuation are predictive of CMV-dz risk. METHODS: Plasma IL-10 levels were quantitatively measured by ELISA kit in 40 D/R SOT patients. All 40 D/R high-risk patients were prospectively followed for at least 12 months post-SOT: 13 subjects developed CMV-dz, all within 6 months of prophylaxis discontinuation. RESULTS: IL-10 was detectable at the first post-prophylaxis measurement for 11 of 13 subjects who developed CMV dz. In contrast, IL-10 was detectable in only 6 of 27 CMV asymptomatic patients. Monitoring IL-10 plasma levels within 1 month prophylaxis suspension appeared to have clinically useful level of 85% sensitivity and 78% specificity. CONCLUSIONS: The exact role of IL-10 with its multiple immunoregulatory effects during CMV infection is not clear. Moreover, IL-10 production can be influenced by pathological and infectious contexts, and/or anti-rejection immunosuppressant therapy. Despite mechanisms of IL-10 dysregulation may substantially differ among SOT patients, our findings suggest that measurable plasma IL-10 soon after prophylaxis discontinuation may be an adequate indicator of subsequent CMV-dz. If a similar prognostic performance is confirmed in a larger D/R cohort, IL-10 plasma levels could be used to guide the length of prophylaxis, providing a clinically useful means to reduce the incidence of CMV-dz in high risk patients. PMID- 26680377 TI - Systematic Review of Randomized Controlled Trials Comparing Manual Compression to Vascular Closure Devices for Diagnostic and Therapeutic Arterial Procedures. AB - PURPOSE: A multitude of vascular closure devices (VCDs) are currently on the market for femoral arteriotomy closure after diagnostic and interventional angiography. Randomized, controlled trials (RCTs) comparing these devices to manual compression (MC) and their effect on time to hemostasis, time to ambulation, time to discharge, and immediate as well as long term complications have been studied. A systematic and through review of these evaluations and outcomes has not previously been performed. MATERIALS AND METHODS: A systematic review was completed to include all available RCTs comparing vascular closure device use to manual compression. Devices meeting inclusion criteria were as follows: VasoSeal(r) (Datascope Corporation, Montvale, NJ), AngioSealTM (Sherwood Davis & Geck, St Louis, MO/St Jude Medical, St Paul, MN), ProGlide(r) (Abbott Vascular, Abbott Park, IL), ProStar(r) (Abbot Vascular, Menlo Park, CA), StarClose SE(r) (Abbott Vascular, Redwood City, CA), ExoSealTM (Cordis, Warren, NJ), BoomerangTM Wire (Cardiva Medical, Mountainview, CA), FemoSealTM (St Jude Medical Systems, Uppsala, Sweden), EVSTM (expanded vascular stapling, Angiolink Co, Taunton, MA), X-PRESSTM (X-Site Medical, Blue Bell, PA), DuettTM (Vascular Solutions, Minneapolis, MN), EpiClose-T(r) (CardioDex Ltd., Tirat Ha Carmel, Israel), and FISHTM (femoral introducer sheath and hemostasis, FISH Device, Bloomington, IN). Vascular closure devices were compared both to manual compression and across all devices used for the following outcomes: time to hemostasis, time to ambulation, time to discharge, and outcomes such as bleeding, hematoma, pseudoaneurysm, limb ischemia, and overall major and minor complications, as well as impact on quality of life, cost analysis, and trends over time. Both diagnostic and interventional procedures were included. RESULTS: PUBMED and MEDLINE searches were carried out for VCDs identifying 1,363 articles. Manuscripts that included manual compression in the study numbered 176. Of these, 34 randomized controlled trials were included. Studies that met inclusion criteria were published from 1992-2015 and described a total of 14,401 patients, 5,659 patients undergoing MC, and 8,742 patients undergoing VCD placement. Overall, the rate of procedural success for VCD patients was 95.7%. The highest rate of unsuccessful device deployment was seen in the ExoSealTM subset, which averaged 37.9% failure. The overall median time to hemostasis for manual compression was 22.9 minutes compared to VCDs at 5.95 minutes; FemoSealTM had the shortest median time to hemostasis of 0.75 minutes. When comparing the type of procedure and its median time to hemostasis, MC versus VCD was 17 minutes versus 3.7 minutes for diagnostic procedures and 29.1 minutes versus 7.6 minutes for interventional procedures with similar sheath sizes at 6 and 7 French, respectively. Similarly, median time to ambulation for MC was eight hours compared to 3.5 hours for patients who received a VCD. Median time to discharge was similar at 1.6 days. However, time to discharge has diminished over the last decade comparing MC to VCD, with a median time to discharge of 3.1 versus 2.2 days compared to current trends at 0.8 versus 0.5 days, respectively. The overall rates of complications were similar between MC at 13.1% versus VCDs at 12.2% but varied significantly according to the VCD that was selected. For patients randomized to the vascular closure device who had undergone prior angioplasty, 94.4% of these patients preferred the use of VCD if a further angioplasty were to be performed in the future. A 13% reduction in overall costs with VCD was demonstrated due to earlier discharge and less required time with physician and nursing staff. CONCLUSION: Overall, the review of 34 RCTs demonstrates the utility of VCDs has shortened time to hemostasis, ambulation, and discharge compared to patients receiving MC. Over the last decade, with emphasis on and implementation of same-day procedures, use of VCDs has resulted in a reduction in time to discharge to half a day and a significant decrease in cost. Overall complication rates are similar, but vary between different devices on the market. Better short-term quality of life has also been described with the use of VCDs compared to MC. Further clinical and financial improvements may be found as newer technological advances of VCDs become available. PMID- 26680378 TI - The Use of Haemostatic Agents and Sealants for the Prevention of Lymphocele After Urological Surgery: A Review of the Literature. AB - BACKGROUND: Despite the continuous technological innovation in urological surgery procedures, lymphocele represents one of the major and more frequent complications both in tumour and transplant surgery. Haemostatic agents have been used hypothesizing a beneficial effect on the prevention of lymphoceles. We aimed to review the published literature to establish whether haemostatic agents and sealants are an effective option for lymphocele prevention following urological procedure. MATERIALS AND METHODS: An extensive PubMed search was performed including the following keywords: "lymphocele", "lymphocele prevention", "fibrin glue", "collagen patch", "fibrin patch", and "haemostatic material". The search, which collected data until January 2000, was restricted to the full text available articles in the English language and human studies. RESULTS: Our research identified 64 articles, among these only four fulfilled the inclusion criteria. A total of 133 patients underwent surgery and were treated with haemostatic agents and/or sealants to reduce the lymphoceles formation. The mean age was 56.1 years. A negligible variability in study design and in results and complication reporting is common. The 6.45% of patients treated with haemostatic biomaterials developed lymphocele. The rate difference of lymphoceles formation and recurrence between patient groups treated with sealant than in the controls groups is small (6.45% vs 6.88%). CONCLUSIONS: The evidences presented in the examined studies are only preliminary and insufficient to draw significant conclusions. A major, multicentre, randomized controlled trial is strongly needed. PMID- 26680379 TI - An In Vivo Comparison of Hemostatic Gelatin Matrix Products in a Porcine Spleen Biopsy-punch Model. AB - Flowable gelatin matrix products have established themselves as effective, easy to-use hemostatic agents useful in a variety of surgical situations. A recently reformulated gelatin matrix, Surgiflo(r) (Ethicon Inc., Somerville, NJ), can be prepared quickly and provides consistent flow over an 8-hr. period. No in vivo studies have yet been reported comparing hemostasis with the new Surgiflo to other currently marketed flowable gelatin matrix products. This study was conducted to determine whether Surgiflo in actual use has hemostatic qualities different from another commercial gelatin matrix. An in vivo model based on porcine spleen biopsy punch-induced bleeding was used to compare Surgiflo and FlosealTM (Baxter Healthcare Corporation, Hayward, CA), both with thrombin. Time required to achieve hemostasis and proportion of sites achieving hemostasis within 30 s were determined for both hemostatic agents and a control of saline soaked gauze. Results were stratified by the degree of initial bleeding (mild, moderate, severe). Hemostasis was achieved within 3 minutes at all sites for both test products regardless of level of initial bleeding, and control sites continued bleeding past 10 minutes. There were no statistically significant differences between Surgiflo and Floseal for either mean time to hemostasis or proportion of sites hemostatic within 30 s. In this realistic in vivo model both gelatin matrix products were effective, and there were no significant differences observed in hemostatic efficacy between Surgiflo and Floseal. Other factors, such as ease of preparation and application, in-use stability, and economic considerations may affect a surgeon's decision in selection of a desirable hemostatic product. PMID- 26680380 TI - Mini-Laparoscopy: Instruments and Economics. AB - Mini-laparoscopy (Mini) was pioneered more than 20 years ago, initially with instruments borrowed from other specialties and subsequently with tools designed specifically for Mini. Early adoption of Mini was inhibited though by the limitations of these first-generation instruments, especially functionality and durability. Newer generation Mini instruments have recently become available with improved effector tips, a choice of shaft diameters and lengths, better shaft insulation and electrosurgery capability, improved shaft strength and rotation, more ergonomic handles, low-friction trocar options, and improved instrument durability. Improvements are also occurring in imaging and advanced energy for Mini. The current status of mini-laparoscopy instruments and economics are presented. PMID- 26680381 TI - Prospective Clinical Study to Evaluate Clinical Performance of a Powered Surgical Stapler in Video-assisted Thoracoscopic Lung Resections. AB - Video-assisted thoracic surgery (VATS) research often focuses on postoperative air leak, with special consideration for prolonged air leak. There is limited clinical data regarding how stapling devices might affect performance and postoperative outcomes, including air leak. This prospective research evaluates intraoperative and postoperative data associated with VATS, using a new surgical stapling device, in two different geographic regions (the U.S. and Europe). A total of 226 subjects across 10 institutions were enrolled in this study. The primary endpoint was occurrence and duration of postoperative air leaks, including prolonged air leak. Additional data collected included intraoperative details and postoperative outcomes. Prolonged air leak occurred in 22 subjects (10.3%) across procedures (152 lobectomies, 63 wedge resections, and 11 occurrences of wedge resection plus lobectomy). There were no significant differences in occurrence or duration of PAL between the U.S. and Europe. Regional differences were observed for intraoperative leak testing and cartridge selection relative to tissue type. Despite differences in surgical technique between continents, no major or significant difference in air leak or other clinical outcome was detected. Additional research is needed to characterize optimal cartridge selection to tissue properties and how these may potentially impact clinical outcomes. PMID- 26680382 TI - Continuous Intraoperative Neuromonitoring in Thyroid Surgery. AB - Intermittent intraoperative neuromonitoring (I-IONM) has been introduced to thyroid surgery during the past two decades. The neuromonitoring devices (hardware and software) were significantly improved with the development of the second and third device generations. Needle electrodes, which were widely used 10 years ago, are almost completely substituted by less invasive, optimized endotracheal tube electrodes that ensure signal stability. In addition, recommendations of surgical societies for the standardized application of IONM have been established and incorporated into guidelines. However, due to the already very low frequency of (permanent) recurrent laryngeal nerve (RLN) paralysis following primary thyroid resections, a significant benefit of IONM compared to the "gold standard" of visual identification of the RLN alone has not been demonstrated so far. Moreover, the idea to enable surgeons to recognize impending nerve damage during (not after) dissection cannot be implemented with I IONM techniques. The main benefit of I-IONM, therefore, remains the possible change of resection strategy in case of a "loss of signal (LOS)" after resection of one thyroid lobe in patients with planned bilateral resection. The recent introduction of continuous neuromonitoring (C-IONM) represents a significant step forward, potentially enabling the surgeon to react before irreversible damage to the RLN occurs. Preliminary data are supporting this methodological advantage. PMID- 26680383 TI - Technique of Robotic-assisted Total Proctocolectomy with Lymphadenectomy and Ileal Pouch-Anal Anastomosis for Transverse Colitic Cancer of Ulcerative Colitis, Using the Single Cart Position. AB - Robotic surgery offers advantages for operating in a narrow space such as inside the pelvis. We report on the technique of robotic-assisted laparoscopic total proctocolectomy with lymphadenectomy and ileal pouch-anal anastomosis for ulcerative colitis with transverse colitic cancer, using the single cart position. A 46-year-old female patient was diagnosed with colitic cancer of the transverse colon during the surveillance of ulcerative colitis. Six port sites were used. Mobilization of the left-sided colon through to the rectum and mobilization of the transverse colon with lymphadenectomy around the middle colic artery were performed using the robotic surgical system. After rectal mobilization was conducted near the anus, the right side of the colon was mobilized and the ileum resected laparoscopically. Thereafter, a mucosectomy of the proctorectum was carried out through a trans-anal approach, and a hand-sewn J pouch was performed. Finally, a diverting ileostomy was constructed through the right lower abdomen. The operative time was 460 minutes, including the console time of 361 minutes. The amount of blood loss was 76 g. The patient was discharged on postoperative day nine. Pathological results demonstrated that the depth of the lesion was T3, and the positive lymph node was 1 of 115 retrieved lymph nodes. There were no complications or mortality. Robotic-assisted total proctocolectomy and lymphadenectomy with ileal pouch-anal anastomosis for transverse colitic cancer of ulcerative colitis was performed safely using the single cart position. PMID- 26680384 TI - LigaSure Vessel Sealing System in Altemeier's Procedure for Geriatric Patients. AB - The aim of this study is to describe the feasibility, safety, and efficiency of LigaSureTM Vessel Sealing System (LSVSS) in Altemeier's procedure for full thickness rectal prolapse in a geriatric group of octogenarians and older. To the best of our knowledge, this is the first time a study on this procedure looks specifically at a very old patient group and LigaSure. A review of the literature was conducted on Pubmed Database. From April 2008 to October 2013, seven female patients (median age, 89 years) underwent Altemeier's procedure for prolapse using the LSVSS. Preoperative, intraoperative, and postoperative data were collected and analyzed for all patients. Five out of seven patients were ASA class III and had previous history of pelvic surgery. All had preexisting medical conditions other than the full-thickness rectal prolapse. Stapled anastomoses were performed in 6/7 cases with a circular stapling device. The median surgical time was 74 min. and intraoperative blood loss was minimal for all 7 patients. The median length of the resected specimen was 9 cm. There was no surgery-related mortality or recurrence. All patients had at least a 2-year follow-up. The use of the LSVSS in Altemeier's procedure is feasible, safe, and time-saving. PMID- 26680385 TI - Current Developments and Unusual Aspects in Gastrointestinal Surgical Stapling. AB - Stapling devices are used in gastrointestinal, gynecologic, thoracic, and many other surgeries to resect organs, transect tissues, and anastomose different structures. These devices became widely accepted standard practice in many gastrointestinal operations, especially since the successful advent of minimally invasive surgery. Despite the relevant advantages related to the use of a surgical stapler, we must also consider that these instruments may be at risk of failure. When any component fails, the patient is at risk of operative morbidity. Gastrointestinal surgical stapling technique still needs refinement in order to increase its reliability. Staple line reinforcement has been widely used and seems to effectively reduce anastomotic complications. Literature provides us with examples of studies supporting both bleeding and leakage reduction after staple line reinforcement, but high-quality evidence is not available to date. Semi-absorbable and nonabsorbable materials have been the earliest available. The use of bioabsorbable staple line reinforcement materials has recently become more widespread, and these materials are more widely used these days. Powered staplers were made available to the market some time ago and represent a rather unheard of aspect of endosurgical stapling. Despite powered staples being supposedly convenient compared with manual ones only one relevant article was found when searching the U.S. National Library of Medicine for "powered stapler." New surgical stapling devices are constantly developed and introduced on the market. Results with such devices depend on the stapler features but also surely vary according to the surgeon experience. PMID- 26680386 TI - Development of an Ultra-rapid, Small Tissue-collecting Device for Endoscopic Surgery--the Lymph Node Carrier: Useful in Protecting the Air-sealing Valves of the Trocar for Endoscopic Surgery and in Preventing Port Site Recurrence. AB - In laparoscopic and thoracoscopic surgery for malignant tumors, it is often necessary to recognize intraoperative rapid diagnosis by sampling a small section of tissue that is suspected of the lymphatic or disseminated metastasis of malignant tumor cells, or of the direct invasion. However, sampling of the target tissue has to be carried out without dropping a section into the peritoneal or thoracic cavity and port-site tumor recurrence. We developed a device named the "lymph node carrier (LNC)" that is capable of instantaneously carrying a small piece of tissue out of the body after its insertion into the trocar for conventional laparoscopic surgery. LNC is composed of the following three parts: 1) the carrier container; 2) the external sheath that re-encloses the tissue, which protruded from the container, into the container; and 3) the air-sealing cap. In the in vivo study three sows were used to remove the sigmoid colon and to carry adipose tissue containing the dissected lymph nodes out of the body. Sliding of the external sheath and the LNC container allowed the re-enclosure of adipose tissue protruding from the container. Carriage time of the dissected lymph nodes out of three sows was 37.7+/-1.5 seconds in mean+/-SD. LNC was suggested to be a surgical device capable of allowing, in a very efficient manner and a very short period of time, the repeated collection of removed specimens out of the body without damaging the air-sealing valves of the trocar for endoscopic surgery. PMID- 26680387 TI - Self-Retaining Retractor Widox(r) for Thyroid Surgeries: Technical Note. AB - During a thyroidectomy, perfect exposure of the vascular nerve structures, parathyroid gland, trachea, larynx, esophagus, and lymphnodes is crucial to facilitate the surgeon in the meticulous dissection. WIDOX(r) (MOSS Spa, Lesa, Italy) is an atraumatic self-retaining thyroidectomy retractor specifically designed for thyroid surgeries with an octagonal shape and six retractors (Fig. 1). It is a sterile, single-use device which keeps the surgical wound and the neck muscles retracted allowing the proper exposure of the operatory field. The device substitutes the manual retractors held by the surgeon's assistants. In our institute, we started using the self-retaining retractor WIDOX(r) from May 2015 for a total of 50 patients. From our preliminary experience, the self-retaining retractor WIDOX(r) is simple and practical and can be adapted to each patient. The use of energy-based devices and the neuromonitoring is not prevented by the presence of this retractor. PMID- 26680388 TI - A New Bariatric Procedure: The Stomach Sparing Gastric SleeveTM. AB - A new restrictive procedure has emerged over the last decade known as the total vertical gastric plication or greater curvature plication (GCP). After our initial experience, the original technique was modified and a new standardized procedure was registered as the Stomach Sparing Gastric SleeveTM (SSGS). The SSGS reduces the capacity of the stomach by in-folding the greater curvature with containment sutures, creating a sleeve-like stomach. Between March 2012 and August 2015 patients that met the National Institutes of Health (NIH) criteria for gastric banding underwent treatment with the SSGS. The standardized technique requires the use of a customized fenestrated orogastric calibration device. The stomach is then imbricated or in-folded in two layers and containment non absorbable sutures are placed longitudinally. The two layers of non-absorbable sutures are continuous starting 1 cm below the esophageal gastric (EG) junction and continued distally 3-4 cm from the pylorus spaced evenly at 1 cm intervals and sero-muscular thickness. Symmetry of anteroposterior distribution is also observed leading to the formation of a sleeve-like shaped stomach. Initial and subsequent weight (kg), body mass index (Kg/m2), excess weight loss (%EWL) and complications were recorded. Repeated measures of analysis of variance (ANOVA) were used to assess weight change. The SSGS was performed on the last 624 cases (mean age 43.1+/-11.6 years). The follow-up time was 3 years, with an %EWL of 56.36+/-21.83 during the first year and a maintenance of 49.37+/-30.82 by the third year of follow-up (p=<0.0005). Patients with a BMI of 20-30 Kg/m2 had an EWL of 60.46% during the first 6 months after surgery and an EWL of 74.84% in the first year and a maintained EWL after 3 years of 60.45%. The surgical mean time was 45 min. There were no conversions to the open approach. A 0% mortality and 1.12% morbidity were reported. The SSGS has a weight loss comparable to other restrictive procedures, with excellent mid-term excess weight loss in the 20-30 Kg/m2 BMI category. This new technique is an improvement over the original technique, as it has been modified specifically to address the complications of the original non-standardized gastric plication. The benefits of this restrictive technique are that it requires no stapling, dividing, or rerouting of the intestines, as well as no need to implant a foreign body device. The disadvantages observed were a steep learning curve and lack of a standardized technique until this publication. PMID- 26680389 TI - Innovations in Bariatric Surgery. AB - Surgery has consistently been demonstrated to be the most effective long-term therapy for the treatment of obesity. However, despite excellent outcomes with current procedures, most patients with obesity- and weight-related comorbidities who meet criteria for surgical treatment choose not to pursue surgery out of fear of operative risks and complications or concerns about high costs. Novel minimally invasive procedures and devices may offer alternative solutions for patients who are hesitant to pursue standard surgical approaches. These procedures may be used for primary treatment of obesity, early intervention for patients approaching morbid obesity, temporary management prior to bariatric surgery, or revision of bypass surgery associated with weight regain. Novel bariatric procedures can in general be divided into four categories: endoluminal space-occupying devices, gastric suturing and restrictive devices, absorption limiting devices, and neural-hormonal modulating devices. Many of these are only approved as short-term interventions, but these devices may be effective for patients desiring low-risk procedures or a transient effect. We will see the expansion of indications and alternatives for metabolic surgery as these techniques gain approval. PMID- 26680390 TI - Antibiotic Coating of Hernia Meshes: The Next Step Toward Preventing Mesh Infection. AB - Mesh bacterial colonization/infection remains a critical issue in complex ventral hernia repair. Despite the recent emergence of biologic meshes, current strategies to prevent and treat mesh infection are largely ineffective, often leading to device failure and subsequent explantation along with the associated costs and effect on patient welfare. Unacceptably high rates of morbidity and hernia recurrence following mesh infection highlight the need for innovation in the area of hernia repair for the complex patient. One recent strategy to address such shortcomings is local antibiosis in the form of polymer coatings applied to the mesh itself. Current literature regarding the use of antibiotic-coated hernia mesh is limited but does illustrate the ability of these devices to inhibit bacterial growth and prevent mesh infection in both in vitro and in vivo studies. Although there is a paucity of literature regarding long-term clinical efficacy, this provides opportunity for further inquiry into a promising new development to combat mesh infective complications. PMID- 26680391 TI - Does Laparoscopic Hysterectomy Increase the Risk of Vaginal Cuff Dehiscence? An Analysis of Outcomes from Multiple Academic Centers and a Review of the Literature. AB - Vaginal cuff dehiscence represents a serious, but infrequent complication after hysterectomy, with a reported increased incidence following a laparoscopic approach. Various risk factors have been proposed including laparoscopically placed suture, surgical experience, use of electrosurgery, surgical indication, and obesity. Technical aspects of the procedure itself have also been questioned such as the variable use of monopolar electrosurgery during colpotomy and the suture type or number of layers chosen to reapproximate the vaginal cuff. Nothwithstanding the tendency for cuff dehiscence to occur following laparoscopic approach, there remains a paucity of high-quality data that supports or refutes this finding or clearly defines the mechanism(s) by which this event occurs allowing for the proposal of objective guidelines for reducing risk. Various techniques have been proposed to decrease the risk of vaginal cuff dehiscence during endoscopic hysterectomy, including use of monopolar current on cutting mode, achievement of cuff hemostasis with sutures rather than electrocoagulation, use of a two-layer cuff closure with polydioxanone suture, and use of bidirectional barbed suture for cuff closure. The authors experience at three university-based minimally invasive gynecologic surgery programs showed a low rate of vaginal cuff dehiscence in their own practices. Large randomized controlled trials are needed to truly determine whether there is a difference in vaginal cuff dehiscence between surgical modalities for hysterectomy as well as to determine the true risk factors. PMID- 26680392 TI - Laparoscopic Neurolysis of Deep Endometriosis Infiltrating Left Femoral Nerve: Case Report. AB - Pelvic endometriosis may infiltrate somatic nerves causing severe neuropathic symptoms with a high impact on quality of life. It is a medical condition poorly known, and few published data about involvement of femoral nerve are available. We report an isolated unilateral endometriosis lesion of the left lumbar region infiltrating the femoral nerve in a 38-year-old woman. She described severe dysmenorrhea, dyspareunia, dischezia, and chronic pelvic pain with irradiation to the anterior part of the left thigh. After investigation, it was identified as a 5-centimeter endometriotic nodule involving the femoral nerve and the psoas muscle. The patient was treated by two laparoscopic surgeries with neurolysis of the involved somatic nerve by a multidisciplinary team, with improvement of the symptoms. Laparoscopic neurolysis is the first approach advocated in these cases, leading to relief of neurological symptoms resulting from nerve infiltration by endometriosis. PMID- 26680393 TI - Laparoscopic Paravaginal Defect Repair: Surgical Technique and a Literature Review. AB - Paravaginal defects, commonly seen in patients with anterior vaginal wall prolapse, are due to the detachment of pubocervical fascia from the arcus tendineus fascia pelvis (ATFP), at or near its lateral attachment. The majority of anterior vaginal wall prolapse is thought to be caused by paravaginal defects. Richardson et al. first described and demonstrated the anatomy of the paravaginal defect, as well as described the initial technique of the abdominal approach to repair. Since that time, the laparoscopic approach for repair has been developed and described with success rates of laparoscopic paravaginal defect repair reported in the range of 60% to 89%. This minimally invasive approach to address anterior wall prolapse eliminates the need for a vaginal incision, reduces risk of vaginal shortening and can be completed at the same time as other laparoscopic procedures, such as hysterectomy, sacralcolpopexy, and/or Burch Urethropexy. Compared to the open abdominal approach, there is improved visualization, less risk of bleeding, and faster recovery with the laparoscopic method. Compared to an anterior colporrhaphy, laparoscopic paravaginal repair is a much more anatomic repair of lateral defects and does not result in vaginal shortening. The laparoscopic paravaginal repair should be considered as the first-line treatment of anterior vaginal wall prolapse caused by lateral defects, including at time of laparoscopic/robotic sacralcolpopexy. PMID- 26680394 TI - Postcoital Sperm Assessment Comparative Study. AB - This postcoital sperm assessment study was performed over a 10 month time period (November 2014-August 2015). Fifteen couples enrolled in the study. The study was a non-blinded, non-randomized, single-center comparison study comparing The Stork(r) OTC (Rinovum Women's Health, Monroeville, PA) to natural intercourse (NI), using the subjects as their own control/baseline. This was an efficacy study designed to compare the number of sperm in the cervical mucus following the use of The Stork OTC conception aid with the number of sperm in the cervical mucus following natural intercourse. Subjects used both The Stork OTC conception system and the natural intercourse method to evaluate concentrations of sperm in the cervical mucus. Post-coital test (PCT) data was collected demonstrating higher concentrations of sperm within the cervical mucus with The Stork OTC conception system versus natural intercourse for 85% of test subjects in this study. Of the 15 couples enrolled in the study, 2 were lost to follow-up. Mean age for male subjects was 31.7 +/ 5.4 years of age and mean age for female subjects was 29.7+/- 5.4. The average sperm score value of the 85% of test subjects with higher sperm concentrations from The Stork OTC was 3.23 times the score value of sperm concentration compared to natural intercourse. The remaining 15% of test subjects showed no change in sperm score value between The Stork OTC and natural intercourse. PMID- 26680395 TI - Classification of Hypertrophy of Labia Minora: Consideration of a Multiple Component Approach. AB - Labia minora hypertrophy of unknown and under-reported incidence in the general population is considered a variant of normal anatomy. Its origin is multi factorial including genetic, hormonal, and infectious factors, and voluntary elongation of the labiae minorae in some cultures. Consults with patients bothered by this condition have been increasing with patients complaining of poor aesthetics and symptoms such as difficulty with vaginal secretions, vulvovaginitis, chronic irritation, and superficial dyspareunia, all of which can have a negative effect on these patients' sexuality and self esteem. Surgical management of labial hypertrophy is an option for women with these physical complaints or aesthetic issues. Labia minora hypertrophy can consist of multiple components, including the clitoral hood, lateral prepuce, frenulum, and the body of the labia minora. To date, there is not a consensus in the literature with respect to the classification and definition of varying grades of hypertrophy, aside from measurement of the length in centimeters. In order to offer patients the most appropriate surgical technique, an objective and understandable classification that can be used as part of the preoperative evaluation is necessary. Such a classification should have the aim of offering patients the best cosmetic and functional results with the fewest complications. PMID- 26680396 TI - Laparoscopic Approach for Fibroid Removal at 18 Weeks of Pregnancy. AB - Leiomyomas are the most frequently solid tumors found in pregnancy. This kind of tumor has a wide incidence depending on the age, race, and type of population studied. Most of the cases have an asymptomatic course; however, they could develop different kinds of complications during the pregnancy such as severe abdominal pain, often due to degeneration or torsion with ischemia. In these cases, a surgical approach is required because these tumors do not respond to the conventional treatment. Very few of these cases are reported in the literature. We report the case of a 36-year-old woman pregnant 18 weeks, who experienced acute abdominal pain without initial reponse to regular analgesics. She was taken to the operating room, and under laparoscopic exploration, torsion of a subserosal myoma was observed. The fibroid was resected laparoscopically, and she was released from the hospital without complications. Unfortunately, she was readmitted 45 days later with signs of preterm labor because of a motorcycle accident. An emergency cerclage was performed, but the pregnancy was compromised with amnionitis and early fetal demise. We concluded that the laparoscopic approach could be a successful alternative treatment in selected cases. PMID- 26680397 TI - Now You See It: Using Angled Laparoscopes in Minimally Invasive Gynecologic Surgery. AB - As minimally invasive gynecologic surgery (MIGS) becomes more complex, and cases more difficult, surgeons must adapt to the challenges not only by using innovative equipment but also using the lessons learned from other disciplines. Many years after general surgeons learned the "art of laparoscopy," it is clear that general surgeons in the United States-and those around the world-have surpassed the "masters of laparoscopy" (gynecologists) with their use of new techniques and new equipment. Surgeons are using less traumatic graspers and perform a higher percentage of surgeries laparoscopically than gynecologic surgeons. With the essential need for more integrated ergonomics and a suitable laparoscopic operating room environment, this article describes the benefits of using angled laparoscopes and includes basic techniques to enable gynecologic surgeons to master "driving" the angled laparoscope. PMID- 26680398 TI - Drug-Eluting Stents: New Tools for the Armamentarium Against Peripheral Arterial Disease. AB - With the growing epidemic of diabetes and hyperlipidemia, there is an ever increasing prevalence of peripheral arterial disease (PAD) of the lower extremities. The complications of PAD can be devastating and can increase the economic burden on the healthcare system. Traditionally, open revascularization procedures have been the mainstay of treatment for lower extremity PAD. Cardiac comorbidities are common among patients with PAD and as such may prohibit open revascularization. With the advent of minimally invasive endovascular procedures, the threshold for revascularization opportunities has increased. Despite promising early results of percutaneous transluminal angioplasty (PTA), atherectomy, and stenting, long-term outcomes are hindered by neointimal hyperplasia, which accounts for high restenosis and thrombosis rates. The utility and efficacy of drug-eluting stents in decreasing restenosis rates has been well demonstrated for coronary artery disease. This article will present a review of the current literature available on the use of drug-eluting (polymer-free) and drug-coated (polymer) stents for lower extremity PAD. PMID- 26680399 TI - Prospective Randomized Controlled Trial of Two Different Intramedullary Nails for Pertrochanteric Fractures of the Femur. AB - The purpose of this prospective randomized trial was to assess whether an intramedullary nail is superior or not to another one in the treatment of pertrochanteric fractures. Eighty-one patients with a 31-A1 or A2 Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) pertrochanteric fracture were randomly allocated to fixation with either the Gamma(r) or the ENDOVIS(r) nail. In order to estimate the functional outcome the Parker-Palmer mobility score, Barthel Index, and EuroQol-5D (EQ-5D) were used. All patients were followed up at 1, 3, 6, and 12 months postoperatively. There was no statistical difference in Parker mobility score between groups. The statistical analysis revealed that there was no significant difference between the two patient groups as far as the operating time, the amount of blood transfused, and the latest functional outcome. Both kinds of intramedullary nails used in our study provide effective methods of treatment for intertrochanteric fractures in elderly patients. Our data showed slightly worse results for the ENDOVIS nail compared with the Gamma nail, but this did not reach a statistical significance. PMID- 26680400 TI - Readmission Rates in Patients Who Underwent Total Hip Arthroplasty. AB - Readmission rates remain a concern following total hip arthroplasty (THA). This study: 1) evaluated 30-day, 90-day, and total readmission rates after THAs; 2) assessed causes of readmission; 3) determined differences in demographic factors between those who were and were not readmitted; and 4) compared readmission rates to other large-scale studies. We retrospectively reviewed 232 primary THAs (224 patients) using the same prosthesis at 7 institutions. This included 79 men and 145 women who had a mean age of 69 years (range, 44 to 88). Descriptive analyses were used to evaluate readmission, and rates were compared with those from large cohort studies. There were 11 unplanned readmissions (4.7%) in 10 patients during the first 90 days post-discharge. Seven (3%) readmissions were due to surgical and 4 (1.7%) were due to medical reasons. Surgical causes were found in 70% of early (0 to 30 days) readmissions but none of late (60 to 90 days) readmissions. No differences existed in mean age, gender, and body mass index between readmitted patients and the remainder of the population. We observed lower readmission rates when compared with large cohort studies. The positive performance of the prosthesis may have contributed to the lower readmission rates. PMID- 26680401 TI - Evaluating the Native Length-Tension Relationship in Arthroscopic Suprapectoral Biceps Tenodesis: An MRI Assessment of Contralateral Shoulders. AB - BACKGROUND: Successful tenodesis of the proximal biceps relies on accurate reproduction of the native length-tension relationship of the long head of the biceps (LHB). While open tenodesis procedures can reproduce this relationship by referencing the position of the LHB musculotendinous junction (MTJ) to a visible anatomic landmark, arthroscopic suprapectoral tenodesis does not afford such advantage because the MTJ is usually not visible. No studies to date have evaluated the position of the MTJ of the LHB following arthroscopic suprapectoral biceps tenodesis. METHODS: Patients undergoing arthroscopic suprapectoral biceps tenodesis between January 2013 and May 2014 at one center were evaluated for inclusion. Patients included in the study underwent a postoperative MRI of bilateral shoulders. The distance from the superior portion of the humeral head to the LHB MTJ was measured bilaterally. The measurements from each matched pair were compared using a paired t-test to determine if arthroscopic suprapectoral biceps tenodesis anatomically restored the LHB length-tension relationship. RESULTS: A total of 17 patients met the inclusion criteria. Fourteen of the seventeen patients underwent a postoperative MRI of bilateral shoulders. The distance from the superior portion of the humeral head to the LHB musculotendinous junction was significantly larger on the operative side when compared to the nonsurgical side (operative side mean 98.34 mm, standard deviation 13.38 mm; nonsurgical mean 87.26 mm, standard deviation 9.09; mean difference 11.08 mm; p=0.0105). CONCLUSION: The musculotendinous junction of the LHB in patients who underwent arthroscopic suprapectoral biceps tenodesis was located significantly more distal than the contralateral control, as measured on MRI. PMID- 26680402 TI - Do Standard Surgical Guides Produce Accurate and Precise Femoral Bone Resections During Total Knee Arthroplasty? AB - PURPOSE: Accurate alignment and balanced flexion and extension gaps are critical elements in achieving a successful outcome following total knee arthroplasty (TKA). The ability to make accurate and precise bone cuts is essential in the creation of balanced gaps. We sought to determine if one type of modern-day standard surgical instrument using an intramedullary rod and posterior referencing produces accurate and precise distal and posterior femoral bone resections. MATERIALS AND METHODS: Seventy-five consecutive patients undergoing TKA were divided into three groups, with 25 patients in each group receiving one of three implant designs: 25 Stryker Triathlon(r) CR (Stryker, Mahwah, NJ), 25 Zimmer NexGen(r) Flex CR (Zimmer, Warsaw, IN), and 25 StelKast Proven Gen-FlexTM CR (StelKast, Pittsburgh, PA). Flexion-extension gap matching was determined using only the medial flexion and extension gaps. Accuracy was determined by comparing actual resection thickness to desired resection thickness. "Optimal" accuracy was considered to be within 1.0mm of desired, and "near-optimal" accuracy was considered to be within 2.0mm of the desired resection thickness. Precision was determined by the variability of resection thicknesses within each system. RESULTS: Data demonstrated a lack of accuracy and precision across all three tested systems, with each system resulting in certain unique tendencies. Only one out of 75 cases resulted in optimal resection accuracy with all three cuts (Zimmer). When lowering the threshold to include both optimal and near optimal (within 2 mm of error) with all three cuts, only one third of Stryker and Zimmer cases and two thirds of StelKast cases achieved this threshold, representing 44% of cases (33/75). CONCLUSIONS: Improvements in instrumentation to increase accuracy and precision may be warranted. Errors in fixation may be due to the instrumentation itself, and altering instrumentation to include less modularity, provide more stable fixation, and more reliably seal the implant on the femur may be of benefit. PMID- 26680403 TI - Liposomal Bupivacaine Suspension, Can Reduce Length of Stay and Improve Discharge Status of Patients Undergoing Total Hip Arthroplasty. AB - INTRODUCTION: To ensure good rehabilitation and improved outcomes following total hip arthroplasty (THA), optimal pain control is necessary. Newer methods of pain control have been advocated, as current modalities have been associated with undesirable side effects and serious complications. One such modality is liposomal bupivacaine, which provides long-acting, slow-release analgesia. The purpose of this study was to evaluate: (1) lengths of hospital stay and (2) the discharge status of patients who underwent THA with liposomal bupivacaine compared to a cohort who received standard analgesic regimens. MATERIALS AND METHODS: We utilized a hospital discharge database from July 1, 2013 to June 30, 2014, which included 7,704,919 patients for our analysis. We selected patients aged 18 years or older who had an inpatient stay for THA using ICD-9 procedure code (ICD-9-CM = 81.51), which resulted in 55,129 THA patients. Patients who had a nerve block in the time period from the surgery date to the discharge date were then excluded, which resulted in 54,604 THA patients. The THA cohort who received liposomal bupivacaine suspension consisted of 5,267 patients (2,907 women; 2,360 men) who had a mean age of 64 years, while the THA without injections or nerve block consisted of 49,337 patients who had a mean age of 65 years that consisted of 27,530 women and 21,807 men. We analyzed length-of-stay by controlling for race, region, age, sex, Charlson Index, and operating time using a log link linear model with a negative binomial distribution. The discharge status to home compared to short-term nursing facility or rehabilitation was analyzed using logistic regression while controlling for the aforementioned covariates. RESULTS: The mean lengths of stay, after adjusting for covariates, for the liposomal bupivacaine cohort was significantly shorter than the no injection cohort. The distribution of patients being discharged to home compared to a short-term nursing facility or a rehabilitation facility was higher in the liposomal bupivacaine cohort compared to the cohort who did not receive liposomal bupivacaine. Multivariate logistic regression analyses demonstrated a higher likelihood of being discharged to home in liposomal bupivacaine cohort when compared to no injection. CONCLUSION: Liposomal bupivacaine appears to be an effective pain relief modality that leads to reduced lengths of hospital stay and increased rates of discharge to home. This may be an appropriate addition for the analgesic armamentarium in patients who undergo THA. PMID- 26680404 TI - Porous Tantalum Buttress Augments for Severe Acetabular Posterior Column Deficiency. AB - In revision total hip arthroplasty (THA), consensus is lacking regarding the optimal method for reconstruction of the most severe acetabular defects. Porous tantalum (TM) buttress augments were designed for the most severe postero superior defects. The purpose of this study was to report the results of a consecutive series of acetabular reconstructions utilizing TM buttress augments. Eight complex acetabular reconstructions utilizing a TM buttress augment were performed at two centers. All were Paprosky 3A or Paprosky 3B bone loss classification, with severe superior and posterior column deficiency where wedge augments were insufficient for mechanical support. The acetabular cup sizes ranged from 64-78, and a buttress shim was used in 7 of 8 cases. Clinical and radiographic follow-up averaged 16.5 months (range, 10-28) and no cases were lost to follow-up. There were no cases of clinical or radiographic loosening, and no case had required reoperation or revision. All patients except one were ambulating with either no assist device or a single cane at final follow-up. There was one complication of an iliac wing fracture noted incidentally on postoperative x-rays in the lone patient in whom a buttress shim was not used. At short-term follow-up, TM acetabular buttress augments appear to effectively substitute for the use of structural allografts or cages, which would otherwise be used in this challenging setting. The potential for biologic fixation is promising for the durability of these reconstructions; however, longer-term follow-up is required for full evaluation. PMID- 26680405 TI - Pseudotumor Formation in a Metal-on-polyethylene Total Hip Arthroplasty Due to Trunnionosis at the Head-neck Taper. AB - We present here a case of pseudotumor formation likely due to metal wear debris generated at the head-neck taper (trunnion) of the femoral stem and head components in a metal-on-polyethylene (MOP) total hip arthroplasty. Over the last few years, this recently described diagnosis, trunnionosis, has been recognized and reported more frequently. This patient presented with a rather large (12-cm diameter) pseudotumor with accompanying loss of abductors and a pelvic discontinuity making reconstruction more challenging. We believe the psuedotumor in this patient developed from trunnionosis. This is an interesting case of aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) in a MOP total hip arthroplasty. PMID- 26680406 TI - A Comprehensive Assessment of Various Outcome Scores to Evaluate Total Hip Arthroplasties. AB - INTRODUCTION: Many scoring systems have been developed that serve to evaluate outcomes following total hip arthroplasty (THA). However, most systems focus on specific aspects of a patient's recovery rather than investigating a broad spectrum of parameters, which prevent physicians from obtaining a sufficient impression of a patient's recovery. Therefore, we evaluated existing scoring systems to assess the outcome categories included and parameters of interest. MATERIALS AND METHODS: We examined all hip scoring systems currently available in the literature. The outcomes measured in each scoring system were sub-classified into one of four categories; subjective, objective, rehabilitative, and quality of life. We determined the number of scoring systems that incorporated each of these four categories and we assessed the most common parameters in each. The categories and individual parameters were assigned a relative weighted mean score based on how often they were incorporated, in an effort to determine their importance. RESULTS: We identified 42 hip scoring systems consisting of 44 individual parameters, which were divided into the above four categories. Of the relevant scoring systems, 74% included subjective parameters, 31% included objective parameters, 90% included rehabilitative parameters, and 62% included quality of life parameters. The most commonly assessed subjective parameters include pain, stiffness, and general hip difficulty. The most commonly assessed objective parameters include general/combined ROM, flexion/extension, and abduction/adduction. The most commonly assessed rehabilitative parameters include the ability to walk, the ability to climb stairs, and the ability to reach to the floor. The most commonly assessed quality of life measures include the ability to use a car, performance of light domestic duties, and performance of heavy domestic duties. The category of rehabilitative practices carried the greatest weighted mean (49%) in hip scoring systems, followed by subjective (40%), quality of life (6%), and objective (5%). With regard to individual hip outcome parameters, pain carried the greatest weighted mean (23%), followed by the ability to walk and the ability to perform general activities (11% each). CONCLUSION: Patient outcomes can be evaluated by the use of scoring systems in an effort to determine the effectiveness of THA in regaining function and improving quality of life. Determining the frequency and importance of parameters in current scoring systems may allow for a more accurate and purposeful assessment of post-operative function and patient satisfaction. Understanding what is evaluated in existing scoring systems may shed light on the future development of a comprehensive outcome questionnaire. PMID- 26680407 TI - The Institutional Costs and Resource Profile of Transfer Patients Into an Arthroplasty Service. AB - The decision point with inter-hospital arthroplasty patient transfers and its financial implications have not been well studied. Factors outside of complexity of medical and surgical care are believed to drive the transfer of orthopaedic patients to tertiary care centers. We compared our institutional cost and resource utilization between transfer and elective patients in need of arthroplasty care. We hypothesized that transfer patients will incur a higher direct cost and resource utilization compared to elective patients, and that socioeconomic factors will play a role in the decision of transfer. After analysis of key metrics, transfer patients at our institution did not have any significant differences in insurance types. However, they did incur a longer length of stay (p<0.0001) and incurred greater direct costs (p<0.0001) to the hospital. After analysis of key parameters, transfer patients were more complex and costly to care for compared to our in-system patients. PMID- 26680408 TI - Early Experience with a New Porous Hemispheric Acetabular Component. AB - A third-generation cementless acetabular system has been designed, building on the successes of a second-generation system that featured good congruity between the liner and hemispheric shell, and proven porous plasma-sprayed coating on titanium alloy substrate, by designing a ringless barb and groove locking mechanism and optimizing range of motion. These design features are amenable to modern, highly crosslinked polyethylenes. A retrospective review was performed to assess early outcomes. A query of our practice registry revealed 534 patients (576 hips) who underwent cementless total hip arthroplasty performed by three surgeons with the G7TM Acetabular System (Biomet, Warsaw, Indiana) between April 2013 and March 2014. All liners were vitamin E infused, highly crosslinked polyethylene with a neutral face. Heads used were 463 BIOLOX(r) delta (81%; CeramTec AG, Plochingen, Germany) and 112 cobalt-chromium (19%), with diameters of 32 mm in 238 (41%), 36 mm in 331 (58%), and 40 mm in 6. Minimum one-year follow-up was available for 400 hips. Mean follow-up was 15 months (range 10-24, SD 3.0). Harris hip scores improved from 50.7 preoperatively to 86.5 most recently. UCLA activity scale improved from 4.5 preoperatively to 5.4 most recently. Two patients required cup revision secondary to failure of biological fixation at 8.4 and 15.1 months respectively. Radiographic findings in all cases were satisfactory position and alignment with no radiolucencies observed. In this group, with very early follow-up, good results with a low rate of acetabular revision and no dislocations were achieved using a new hemispheric porous shell with ringless barb and groove locking mechanism and geometry. PMID- 26680409 TI - Decreased Opioid Utilization and Cost at One Year in Chronic Low Back Pain Patients Treated with Transcutaneous Electric Nerve Stimulation (TENS). AB - INTRODUCTION: Chronic low back pain (CLBP) may be treated without opioids through the use of transcutaneous electrical nerve stimulation (TENS). However, no study has evaluated its clinical effect and economic impact as measured by opioid utilization and costs. The purpose of this study was to evaluate patients who were given TENS for CLBP compared to a matched group without TENS at one-year follow-up, to determine differences between opioid consumption. MATERIALS AND METHODS: Opioid utilization and costs in patients who did and did not receive TENS were extracted from a Medicare supplemental administrative claims database. Patients were selected if they had at least two ICD-9-CM coded claims for low back pain in a three-month period and were then propensity score matched at a 1:1 ratio between patients who received TENS and those who did not. There were 22,913 patients in each group who had a minimum follow-up of one year. There were no significant demographic or comorbidity differences with the exception that TENS patients had more episodes of back pain. RESULTS: Significantly fewer patients in the TENS group required opioids at final follow-up (57.7 vs. 60.3%). TENS patients also had significantly fewer annual per-patient opioid costs compared to non-TENS patients ($169 vs. $192). There were significantly lower event rates in TENS patients compared to non-TENS patients when measured by opioid utilization (characterized by frequency of prescription refills) (3.82 vs. 4.08, respectively) or pharmacy utilization (31.67 vs. 32.25). The TENS group also demonstrated a significantly lower cost of these utilization events ($44 vs. $49) and avoided more opioid events (20.4 events fewer per 100 patients annually). DISCUSSION: Treatment of CLBP with TENS demonstrated significantly fewer patients requiring opioids, fewer events where a patient required an opioid prescription, and lower per-patient costs. Since TENS is both non-invasive and a non-narcotic, it may potentially allow physicians to be more aggressive in treating CLBP patients. PMID- 26680410 TI - Repair of Medial Patellofemoral, Ligament Improves Patellar, Tracking in Total Knee Replacement. AB - The medial patellofemoral ligament (MPFL) is essential to maintain patella stability; however, its role in total knee replacement (TKR) has not been studied. Forty-six consecutive TKRs in 40 patients were reviewed. Standard closure was performed in 29 TKRs. The MPFL was isolated and anatomically re approximated in 17 subsequent TKRs. Blinded radiographic evaluation of patellar tilt and subluxation was performed preoperatively and 4 months postoperatively. Despite greater preoperative lateral tilt, the MPFL repair group demonstrated greater correction in patellar tilt compared with the standard closure group (p = 0.02). Patellar tracking also was optimized in the MPFL group, despite equivalent preoperative lateral patellar subluxation in the two groups. Simple repair of the MPFL at arthrotomy closure appears to optimize patellar stability radiographically and may improve long-term results by minimizing patellar complications and wear. PMID- 26680411 TI - Long-term Bone Remodeling in HA-coated Stems: A Radiographic Review of 208 Total Hip Arthroplasties (THAs) with 15 to 20 Years Follow-up. AB - We present a prospective study focused on radiographic long-term outcomes and bone remodeling at a mean of 17.0 years (range: 15 to 20) in 208 cementless fully HA-coated femoral stems (Corail, DePuy International Ltd, Leeds, UK). Total hip replacements in this study were performed by three members of the surgeon design group between 1986 and 1991. Radiographic evaluation focused on periprosthetic osteolysis, bone remodeling, osseous integration, subsidence, metaphyseal or diaphyseal load transfer, and femoral stress shielding. The radiographs were digitized and examined with contrast-enhancing software for analysis of the trabecular architecture. Radiographic signs of aseptic stem loosening were visible in two cases (1%). Three stems (1.4%) showed metaphyseal periprosthetic osteolysis in four of seven Gruen zones associated with eccentric polyethylene wear awaiting metaphyseal bone grafting and cup liner exchange. One stem (0.5%) was revised due to infection. No stem altered in varus or valgus alignment more than two degrees, and mean subsidence was 0.1 mm (range: 0 to 2 mm) after a mean of 17.0 years. A total of 5 stems (2.4%) required or are awaiting revision surgery. Trabecular orientation and micro-anatomy suggested main proximal load transfer patterns in all except 3 cases (98.6%). Combined metaphyseal and diaphyseal osseointegration and bone remodeling were visible in 100 stems (48%). Diaphyseal stress shielding and cortical thickening were observed in 3 stems (1.4%). Other radiographic features are discussed in depth. This long-term study of 208 fully HA-coated Corail stems showed satisfactory osseointegration and fixation in 203 cases (97.6%) after a mean of 17.0 years follow-up. Stem failures were associated with extreme eccentric polyethylene wear. PMID- 26680412 TI - Unloader Bracing for Knee Osteoarthritis: A Pilot Study of Gait and Function. AB - Knee osteoarthritis (OA) is increasing in the United States, and some have proposed the use of unloader bracing as an adjunct to current standard treatments. Our purpose was to evaluate outcomes of this brace for the treatment of knee osteoarthritis compared with standard non-operative treatment. Specifically, we evaluated: (1) pain relief, (2) objective functional improvement, (3) subjective functional improvement, (4) quality of life, (5) isokinetic quadriceps muscle strength, and (6) gait changes. A prospective, randomized, study was performed on 18 patients who had Kellgren-Lawrence grade 1 and 2 osteoarthritis. Patients were randomized to receive either standard treatment or an unloader brace. End points evaluated included: functional tests, Knee Society Score, Short Form 36 (SF-36) health survey, Visual Analog Scale (VAS) for pain, Lower Extremity Functional Scale, isokinetic quadriceps and hamstring muscle strength, and 3-dimensional gait analysis. There were no differences between cohorts in evaluation of pain (VAS), objective functional tests, subjective functional outcomes (Knee Society Scores and LEFS), quality of life assessment with SF-36, isokinetic quadriceps and hamstring muscle strength, and gait parameters. The use of unloader brace demonstrated similar improvements compared with standard treatments for knee osteoarthritis, and we believe that it can be a beneficial or equivalent adjunct to continuum of care for the treatment for knee osteoarthritis. PMID- 26680413 TI - Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection. AB - Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions. PMID- 26680414 TI - Acute Tetraplegia after Posterior Cervical Laminectomy for Chronic Myelopathy. AB - Spinal cord injury (SCI) during revision surgery for persistent multilevel cervical myelopathy (MCM) after an initial anterior procedure is rare. However, the pathophysiology of MCM, even prior to surgery, is a risk-factor for neurological deterioration due to the development of a "sick cord", which reflects pathological changes in the spinal cord that lower the threshold for injury. We report a case of persistent MCM despite a three-level ACDF and corpectomy who developed an incomplete C6 tetraplegia during revision cervical laminectomy and posterior instrumentation. Intraoperative neuromonitoring signal changes occurred in the absence of mechanical trauma. Postoperative MRI of the cervical spine demonstrated increased T2 hyperintensity and cord expansion at C3 and C4 compared to the pre-laminectomy MRI. The patient has not made improvements in her neurological status at 13 months postoperatively. The pathophysiology of MCM is discussed in addition to perioperative imaging, neuromonitoring, and use of steroids. PMID- 26680415 TI - Gastric Wall Thickness in Sleeve Gastrectomy Patients: Thickness Variation of the Gastric Wall. AB - The sleeve gastrectomy has been accepted as a primary bariatric procedure. One of the most feared complications is staple line leakage. It is important to use the right staple sizes to minimize the risk of leak. Knowledge of gastric thickness is important. The goal of this study was to measure the thickness of the gastric wall after elimination of the gastric folds in the mucosa. An electronic thickness gauge was developed that measured the anterior and posterior wall of the fresh stomach specimen together at 5 points at a pressure based on the finger pressure necessary to flatten the gastric folds. Thirty-three fresh specimens were measured. The mean compression pressure was 714 grams, and no difference was found between the 5 measure points. There was a significant difference in stomach wall thickness. The gastric antrum was more than 1 mm thicker than the fundus. No difference was found between BMI groups <40 Kg/m2, 40-50 Kg/m2, or >50 Kg/m2. No bleeding occurred, leakage occurred in 1 case. There is a significant difference in thickness of the stomach wall between the gastric fundus and the antrum. A pressure 2.5 times lower than applied in prior studies was necessary to achieve full tissue compression. Choosing thinner staple sizes for the gastric fundus might be the optimal technique for compression. However, there are several additional factors that influence the risk of staple line leaks. PMID- 26680416 TI - Integrating a Numerical Taxonomic Method and Molecular Phylogeny for Species Delimitation of Melampsora Species (Melampsoraceae, Pucciniales) on Willows in China. AB - The species in genus Melampsora are the causal agents of leaf rust diseases on willows in natural habitats and plantations. However, the classification and recognition of species diversity are challenging because morphological characteristics are scant and morphological variation in Melampsora on willows has not been thoroughly evaluated. Thus, the taxonomy of Melampsora species on willows remains confused, especially in China where 31 species were reported based on either European or Japanese taxonomic systems. To clarify the species boundaries of Melampsora species on willows in China, we tested two approaches for species delimitation inferred from morphological and molecular variations. Morphological species boundaries were determined based on numerical taxonomic analyses of morphological characteristics in the uredinial and telial stages by cluster analysis and one-way analysis of variance. Phylogenetic species boundaries were delineated based on the generalized mixed Yule-coalescent (GMYC) model analysis of the sequences of the internal transcribed spacer (ITS1 and ITS2) regions including the 5.8S and D1/D2 regions of the large nuclear subunit of the ribosomal RNA gene. Numerical taxonomic analyses of 14 morphological characteristics recognized in the uredinial-telial stages revealed 22 morphological species, whereas the GMYC results recovered 29 phylogenetic species. In total, 17 morphological species were in concordance with the phylogenetic species and 5 morphological species were in concordance with 12 phylogenetic species. Both the morphological and molecular data supported 14 morphological characteristics, including 5 newly recognized characteristics and 9 traditionally emphasized characteristics, as effective for the differentiation of Melampsora species on willows in China. Based on the concordance and discordance of the two species delimitation approaches, we concluded that integrative taxonomy by using both morphological and molecular variations was an effective approach for delimitating Melampsora species on willows in China. PMID- 26680418 TI - Herbal medicine use in adults who experience anxiety: A qualitative exploration. AB - Herbal medicine use is widespread and has been reported to be as high as 21% in people with anxiety disorders. Critical thematic analysis was used to explore beliefs and attitudes towards herbal medicines in adults experiencing anxiety. In depth interviews were conducted with eight adults who experienced anxiety and used herbal medicines. Three major themes were found: Herbal medicines being different from pharmaceuticals, evidence and effectiveness, and barriers to herbal medicine use. Within these themes people held beliefs about the safety of natural treatments, valued anecdotes from friends and family as a form of evidence for self-prescribing, and described confusion about herbal medicines and their cost as barriers to using them as a treatment option. The findings will inform future research and provide guidance for health practitioners. PMID- 26680417 TI - A PTK7/Ror2 Co-Receptor Complex Affects Xenopus Neural Crest Migration. AB - Neural crest cells are a highly migratory pluripotent cell population that generates a wide array of different cell types and failure in their migration can result in severe birth defects and malformation syndromes. Neural crest migration is controlled by various means including chemotaxis, repellent guidance cues and cell-cell interaction. Non-canonical Wnt PCP (planar cell polarity) signaling has previously been shown to control cell-contact mediated neural crest cell guidance. PTK7 (protein tyrosine kinase 7) is a transmembrane pseudokinase and a known regulator of Wnt/PCP signaling, which is expressed in Xenopus neural crest cells and required for their migration. PTK7 functions as a Wnt co-receptor; however, it remains unclear by which means PTK7 affects neural crest migration. Expressing fluorescently labeled proteins in Xenopus neural crest cells we find that PTK7 co-localizes with the Ror2 Wnt-receptor. Further, co immunoprecipitation experiments demonstrate that PTK7 interacts with Ror2. The PTK7/Ror2 interaction is likely relevant for neural crest migration, because Ror2 expression can rescue the PTK7 loss of function migration defect. Live cell imaging of explanted neural crest cells shows that PTK7 loss of function affects the formation of cell protrusions as well as cell motility. Co-expression of Ror2 can rescue these defects. In vivo analysis demonstrates that a kinase dead Ror2 mutant cannot rescue PTK7 loss of function. Thus, our data suggest that Ror2 can substitute for PTK7 and that the signaling function of its kinase domain is required for this effect. PMID- 26680420 TI - Physical Activity and Obesity in Pediatric Exercise Science. PMID- 26680419 TI - The Nanoscale Observation of the Three-Dimensional Structures of Neurosynapses, Membranous Conjunctions Between Cultured Hippocampal Neurons and Their Significance in the Development of Epilepsy. AB - The nanoscale three-dimensional structures of neurosynapses are unknown, and the neuroanatomical basis of epilepsy remains to be elucidated. Here, we studied the nanoscale three-dimensional synapses between hippocampal neurons, and membranous conjunctions between neurons were found with atomic force microscopy (AFM) and confirmed by transmission electron microscope (TEM), and their pathophysiological significance was primarily investigated. The neurons and dendrites were marked by MAP-2, axons by neurofilament 200, and synapses by synapsin I immunological staining. In the synapsin I-positive neurite ends of the neurons positively stained with MAP-2 and neurofilament 200, neurosynapses with various nanoscale morphology and structure could be found by AFM. The neurosynapses had typical three-dimensional structures of synaptic triplet including the presynaptic neurite end, synaptic cleft of 30 ~ 40 in chemical synapses and 2 ~ 6 nm in electrical ones, the postsynaptic neurite or dendrite spine, the typical neurite end button, the distinct pre- and postsynaptic membranes, and the obvious thickening of the postsynaptic membranes or neurites. Some membranous connections including membrane-like junctions (MLJ) and fiber-tube links (FTL) without triplet structures and cleft were found between neurons. The development frequencies of the two membranous conjunctions increased while those of the synaptic conjunctions decreased between the neurons from Otx1 knock-out mice in comparison with those between the neurons from normal mice. These results suggested that the neuroanatomical basis of Otx1 knock-out epilepsy is the combination of the decreased synaptic conjunctions and the increased membranous conjunctions. PMID- 26680421 TI - Effect of a 12-Week Low vs. High Intensity Aerobic Exercise Training on Appetite Regulating Hormones in Obese Adolescents: A Randomized Exercise Intervention Study. AB - Little is known about how the intensity of aerobic training influences appetite regulating hormones in obese adolescents. Our goal was to assess the effect of low and high intensity aerobic trainings on food intake and appetite-regulating hormones in obese adolescents. Forty three obese adolescents (age: 13-18y, BMI: 34.48 +/- 3.94 kg/m2) were randomized into high intensity training (HIT; n = 20) or low intensity training (LIT; n = 23) groups for 12 weeks. All participants also received the same nutritional, psychological and clinical counseling. Pre- and postintervention energy intake (EI) and circulating levels of insulin, leptin, peptide YY3-36 (PYY3-36) and ghrelin were measured. Adolescents in the HIT showed a reduction in total EI and an increase in PYY3-36 (p < .05). Aerobic exercise training performed at ventilatory threshold 1 intensity, reduced EI and augmented PYY3-36 in obese adolescents, compared with LIT. The data suggest that HIT and LIT have differential effects in the regulation of appetite signals and subsequent EI in obese adolescents. PMID- 26680422 TI - A new section for and by public health practitioners and decision-makers. PMID- 26680423 TI - Innovations in Policy and Practice: Engaging practitioners as scholars. AB - The Canadian Journal of Public Health is launching a new section entitled Innovations in Policy and Practice, which will be a showcase for and reflection on innovative public health policy and practice in Canada. The section will focus on articles that describe the development and implementation of innovative policies and practices in Canada and/or that reflect on the experience of practitioners in implementation. The section is explicitly intended to attract practitioners as both readers and authors. This will involve a number of innovations for the Journal that will make the role of author easier for practitioners and result in published material that is attractive and useful, while retaining a scholarly approach. In addition, the review process for this section will be oriented to the reality of practice and undertaken by 'practitioner-scholars' in a collegial and non-anonymous manner. PMID- 26680424 TI - The right to a healthy environment: A prescription for Canada. AB - This invited commentary summarizes the need for stronger Canadian environmental laws and policies. The environmental burden of disease in Canada is substantial. In part this is due to environmental laws and policies that are significantly weaker and less effective than corresponding rules in other wealthy industrialized nations. One promising approach is recognition of the right to live in a healthy environment. In particular, constitutional recognition of this right in 100 nations has led to stronger environmental laws, better enforcement of those laws, enhanced public participation in environmental decision-making, and superior environmental outcomes (e.g., faster progress in reducing air pollution and greenhouse gas emissions). In light of Canada's weak environmental record, this potentially transformative approach is particularly promising. PMID- 26680425 TI - Applications of geographic information systems in public health: A geospatial approach to analyzing MMR immunization uptake in Alberta. AB - OBJECTIVE: This study evaluates the temporal, spatial, and spatio-temporal variation of immunization rates for measles, mumps and rubella (MMR) immunization in the province of Alberta. The study uses yearly immunization rate data for Health Zones and Local Geographic Areas (2004-2012), which were obtained from Alberta Health's Interactive Health Data Application (IHDA). METHODS: Spatial analyses include a global spatial analysis, Moran's I, and local indicators of spatial association (LISA) analysis - Getis and Ord's G* - to identify clusters of high or low immunization rates. Spatial methods are then applied to a time series analysis to examine how the immunization rates change over time in conjunction with space. RESULTS: Mapped results indicate decreasing immunization rates over time for the majority of the province where most local geographic areas (LGAs) fall short of the 95% herd immunity threshold. Clusters of high immunization rates in the metropolitan centres, and clusters of low immunization rates in the southern and northern region of the province exist spatially and spatio-temporally. Over time, the high rate clusters are decreasing in size and the low rate clusters are increasing. CONCLUSION: This research provides a localized geographic approach to assessing MMR immunization rates in Alberta. Findings from this research can be used to target public health interventions to specific areas that exhibit the lowest immunization rates. These results can also be used for hypothesis generation in future research on barriers to immunization uptake. PMID- 26680426 TI - Estimated public health impacts of changes in concentrations of fine particle air pollution in Canada, 2000 to 2011. AB - OBJECTIVES: To estimate the public health impacts of changes in fine particle air pollution in Canada between 2000 and 2011, employing nationally comprehensive exposure estimates and quantifying the impacts on life expectancy, mortality and morbidity. METHODS: We employed spatially comprehensive exposure estimates derived from satellite remote sensing to estimate the effects of actual observed changes in concentrations of fine particulate matter (PM), of median aerodynamic diameter <2.5 MUm (i.e., PM2.5), from 2000 to 2011. We estimated changes in life expectancy using standard life table methods and changes in frequency of health outcomes as the product of population, baseline rate of the health outcome and the proportional change in health outcome per specified change in PM2.5 concentration. RESULTS: A population weighted average decrease in PM2.5 of nearly 25% (2.0 MUg/m3) was observed between 2000 and 2011. This was estimated to result in a national population weighted average increase in life expectancy of 0.10 years (95% confidence interval 0.03-0.23; up to 0.34 years in specific census divisions) and reductions in the frequency of mortality and morbidity of up to 3.6%. Increases in PM2.5 up to 3.5 MUg/m3 were observed in some census divisions, particularly in the prairies. CONCLUSION: At the national level, changes in PM2.5 concentrations between 2000 and 2011 were associated with an estimated improvement in national population weighted average life expectancy and a net reduction in mortality and morbidity. Areas that failed to improve or that worsened during this period warrant additional scrutiny to identify options for reducing PM2.5 concentrations. PMID- 26680427 TI - Frequency and risk factors related to smoking in cars with children present. AB - OBJECTIVES: Second-hand smoke (SHS) can attain high concentrations in cars. To protect children's health, nine Canadian provinces have enacted legislation prohibiting smoking in privately owned vehicles when children are present; Quebec is the only province with no such legislation. The objective of this study was to estimate the proportion of smokers in Quebec who smoke while travelling in a private vehicle in which children are present, and to compare the characteristics of smokers who do and do not smoke in cars. METHODS: In 2011-12, 754 daily smokers who recently travelled in a car with children completed a telephone survey in which they reported how frequently they smoked in a car, if there were smoking restrictions, and perceptions about the effectiveness of legislation prohibiting smoking in cars when children are present. RESULTS: Twenty-three percent of daily smokers smoked at least occasionally in their car when children were present. This proportion was higher among smokers who knew that there was no legislation in Quebec prohibiting smoking in cars, compared to smokers who believed that such legislation was already in effect (32% vs. 12%). Smokers with a university degree and those who reported that smoking was prohibited at home were less likely to expose children to SHS in cars. Most daily smokers (75%) believed that legislation would be effective. DISCUSSION: The results of this study suggest that legislation prohibiting smoking in cars is necessary to protect children from SHS, that such legislation would be effective, and that it may be relatively easy to implement. PMID- 26680428 TI - Mental health and substance use in an urban First Nations population in Hamilton, Ontario. AB - OBJECTIVES: Mental health and substance use have been identified as health priorities currently facing Indigenous peoples in Canada; however, accessible and culturally relevant population health data for this group are almost non existent. The aim of the Our Health Counts study was to generate First Nations adult population health data in partnership with the De dwa da dehs ney>s Aboriginal Health Access Centre in Hamilton, Ontario. METHODS: Analysis involved data gathered through respondent-driven sampling. Prevalence estimates and 95% confidence intervals were generated for diagnosis and treatment of a psychological disorder or mental illness, depression, anxiety, post-traumatic stress disorder (PTSD) and suicide, alcohol and substance use, and access to emotional support. RESULTS: Of the 554 First Nations adults who participated in the Our Health Counts study in Hamilton, 42% had been told by a health care worker that they had a psychological and/or mental health disorder. High rates of depression (39%) and PTSD (34%), as well as suicide ideation (41%) and attempts (51%) were reported. Half of the sample reported marijuana use in the previous 12 months, and 19% reported the use of cocaine and opiates. CONCLUSION: First Nations adults living in Hamilton experience a disproportionate burden of mental health and addictions. By working in partnership with urban Aboriginal organizations, it is possible to produce policy- and service-relevant data and address the current deficiency in appropriate mental health and substance use services for urban Aboriginal people. PMID- 26680429 TI - Racial discrimination, post-traumatic stress and prescription drug problems among Aboriginal Canadians. AB - OBJECTIVES: 1) To examine associations between racial discrimination and drug problems among urban-based Aboriginal adults; and 2) to determine whether these associations are best explained by symptoms of psychological stress, distress or post-traumatic stress disorder (PTSD). METHODS: Data were collected through in person surveys with a community-based sample of Aboriginal adults (N = 372) living in a mid-sized city in western Canada in 2010. Associations were examined using bootstrapped linear regression models adjusted for confounders, with continuous prescription and illicit drug problem scores as outcomes. Mediation was examined using the cross-products of coefficients method. RESULTS: More than 80% of Aboriginal adults had experienced racial discrimination in the past year, with the majority reporting high levels in that period. Past-year discrimination was a risk factor for PTSD symptoms and prescription drug problems in models adjusted for confounders and other forms of psychological trauma. In mediation models, PTSD symptoms explained the association between discrimination and prescription drug problems; psychological stress and distress did not. PTSD symptoms also explained this association when the covariance between mediators was controlled. The results also indicate that participation in Aboriginal cultural traditions was associated with increased discrimination. CONCLUSIONS: Most efforts to address Aboriginal health inequities in Canada have focused on the role Aboriginal people play in these disparities. The current findings combine with others to call for an expanded focus. Non-Aboriginal Canadians may also play a role in the health inequities observed. The findings of this study suggest efforts to reduce discrimination experienced by Aboriginal adults in cities may reduce PTSD symptomology and prescription drug problems in these populations. PMID- 26680430 TI - Major urban road characteristics and injured pedestrians: A representative survey of intersections in Montreal, Quebec. AB - OBJECTIVES: In urban settings, pedestrian fatalities and injuries are concentrated on major roads. This study aims to describe urban intersections with major roads (arterials and collector roads) and explore the association between intersection characteristics and injured pedestrians. METHODS: From a stratified random sampling in Montreal, Quebec, 512 intersections were selected and their characteristics collected. The number of injured pedestrians from 1999 to 2008 was obtained from ambulance services. Binomial negative regression models (including IRR: incidence rate ratios) were calculated to determine associations between intersection characteristics and injured pedestrians: i) at all intersections; ii) at intersections with multi-lane roads and iii) at signalized intersections with available vehicle and pedestrian counts. RESULTS: Major intersections had more traffic lanes (3.8 vs. 1.7, p < 0.01) and longer pedestrian crossings (18.8 m vs. 12.7 m, p < 0.01) than minor intersections. Bus stops were also more frequent at these intersections (75% vs. 6%, p < 0.01). Overall, each additional traffic lane was associated with a 75% increase in the number of injured pedestrians (IRR = 1.75; 95% confidence interval [CI] = 1.41 2.18). At intersections with multi-lane roads, a fourth branch (IRR = 2.40; 95% CI = 1.53-3.77), vehicles parked within 5 m of the intersection (IRR = 2.40; 95% CI = 1.64-3.51), and marked crosswalks (IRR = 1.79; 95% CI = 1.08-2.95) significantly increased the number of injured pedestrians. Raised medians had no significant protective effect. CONCLUSIONS: The results show that besides traffic and pedestrian volumes, intersection characteristics contribute to pedestrian injuries. The reduction of traffic lanes, parking prohibition near intersections and implementation of appropriate pedestrian refuge areas would improve pedestrian safety. PMID- 26680431 TI - Alcohol warning label perceptions: Emerging evidence for alcohol policy. AB - OBJECTIVES: Patterns of alcohol and cigarette use and abuse can be considered parallels due to their similar social, biological and epidemiological implications. Therefore, the cross-fertilization of policy research, including health warnings evidence, is justified. The objective of this study was to apply the lessons learned from the tobacco health warnings and plain packaging literature to an alcohol packaging study and test whether labelling alters consumer perceptions. METHODS: Ninety-two adults were exposed to four labelling conditions of bottles for a famous brand of each of wine, beer and hard liquor. Participants were randomly assigned to one of four labelling conditions: standard, text warning, text and image warning, or text and image warning on a plain bottle. Participants then expressed their product-based (i.e., evaluation of the products) and consumer-based (i.e., evaluation of potential consumers of the products) perceptions in relation to each label condition and were asked to recognize the correct health warning. RESULTS: As expected, participants perceived bottles with warnings less positively as compared to standard bottles in terms of product-based and consumer-based perceptions: plain bottles showed the most consistent statistically significant results, followed by text and image warnings, and then text warnings in pair-wise comparisons with the standard bottles. Some support for the impact of plain packaging on warning recognition was also found. CONCLUSION: Unlike previous studies, this study reveals that health warnings, if similar to those on cigarette packs, can change consumer based and product-based perceptions of alcohol products. The study reveals the importance of serious consideration of stringent alcohol warning policy research. PMID- 26680432 TI - Knowledge change associated with participation in prenatal education programs in Ontario: A cohort study. AB - OBJECTIVES: The primary objective was to examine how participation in prenatal programs delivered by Ontario public health units influences pregnant women's pregnancy-related knowledge. Secondary objectives were to examine the socio demographic characteristics of women participating in these programs and assess program satisfaction. METHODS: A cohort study was conducted of 511 adult pregnant women who were registered for a prenatal program within one of seven Ontario public health units. Participants completed a pre-program survey, which examined socio-demographic and pregnancy characteristics, and baseline pregnancyrelated knowledge. After finishing the program, participants completed a post-program survey investigating pregnancy-related knowledge and program satisfaction. Pregnancy-related knowledge was assessed using the Healthy Pregnancies Knowledge Survey, which captures knowledge within three subtopic areas: healthy pregnancies, healthy lifestyles and breastfeeding. RESULTS: Participants demonstrated a significant increase in mean knowledge scores, both overall and across each subtopic area. Most participants reported that their program satisfied their questions either mostly or very well across all content areas examined. CONCLUSION: This study is the first large-scale effort to examine the ability of prenatal programs offered through Ontario public health units to influence clients' pregnancy-related knowledge. These findings contribute to the evidence base for prenatal education program planning. PMID- 26680433 TI - Retail availability and marketing of electronic cigarettes in Canada. AB - OBJECTIVES: Canada is among an increasing number of countries with restrictions on the sale of electronic cigarettes (e-cigarettes). In Canada, e-cigarettes containing nicotine have not been approved for sale; however, e-cigarettes that do not contain nicotine and do not make health claims can be sold. To date, there is little empirical evidence assessing the retail availability and marketing of e cigarettes in countries such as Canada. METHODS: Audits were conducted at 59 brick-and-mortar retail outlets (grocery stores, convenience stores, tobacconist shops and vape shops) in four cities (Vancouver, Toronto, Montreal and Halifax) in August-October 2014. In addition, a total of 21 e-cigarette manufacturer/retailer websites were audited, and inquiries were made as to whether the companies sold nicotine-containing products. RESULTS: Overall, 76% of the retail outlets sold e-cigarette products. Of convenience stores, grocery stores and tobacconist shops with e-cigarettes for sale, the vast majority (94%) sold nicotine-free products only; in contrast, all the vape shops sold at least one nicotine-containing e-cigarette product. Front counter displays were the most common form of in-store promotions and were present in virtually all convenience stores, tobacconist shops and vape shops. Nicotine-containing e-cigarettes were available for purchase at approximately half (52%) of the online e-cigarette retailers surveyed. CONCLUSION: E-cigarettes with and without nicotine are widely available and marketed at a variety of retail outlets in Canada. "Illegal" sales of nicotinecontaining e-cigarettes were predominantly found at vape shops and online outlets, suggesting limited compliance with existing regulations. PMID- 26680434 TI - Public perceptions and scientific evidence for perceived harms/risks of community water fluoridation: An examination of online comments pertaining to fluoridation cessation in Calgary in 2011. AB - OBJECTIVES: To examine the perceived harms/risks of fluoridation as expressed in online forums relating to cessation and aftermath in Calgary, specifically, 1) which harms/risks are mentioned, 2) for those harms/risks, what kinds of evidence are cited, 3) to what extent is scientific literature cited, and what is its quality, and 4) for a subset of harms/risks, what is known from the broader scientific literature? METHODS: Relevant online comments were identified through free-text Internet searches, and those explicitly discussing the harms/risks of water fluoridation were extracted. Types of evidence mentioned were identified, and the scientific papers cited were reviewed. Finally, the broader scientific literature on two of the harms/risks was reviewed and synthesized. SYNTHESIS: We identified 17 distinct groups of harms/risks, which spanned human body systems, the environment and non-human organisms. Most often, no evidence was cited. When evidence was cited, types included individuals viewed as authorities and personal experiences. Reference to scientific articles was rare, and those papers (n = 9) had significant methodological concerns. Our review of scientific literature on fluoride and 1) thyroid functioning and 2) phytoplankton revealed some negative effects of fluoride at concentrations exceeding maximum recommended levels (>1.5 ppm). CONCLUSION: The findings have implications for communication with the public about fluoridation. First, to the extent that the public consults the scientific literature, it is essential that the methodological limitations of a study, as well as its relevance to community water fluoridation, be widely and promptly communicated. Second, scientific evidence is only one component of why some people support or do not support fluoridation, and communication strategies must accommodate that reality. PMID- 26680435 TI - Creating a collective impact on childhood obesity: Lessons from the SCOPE initiative. AB - OBJECTIVES: We describe the processes used in SCOPE, a community-based participatory research (CBPR) initiative, to achieve multisectoral engagement and collective action to prevent childhood obesity. PARTICIPANTS: SCOPE engages representatives from various sectors (local government, health, schools, recreation, local media, early childhood, community services) who influence the environments in which children live, learn and play. SETTING: SCOPE has been implemented in three communities in British Columbia (BC). INTERVENTION: SCOPE (www.live5210.ca) is a multi-setting, multi-component initiative designed to enhance a community's capacity to create and deliver localized solutions to promote healthy weights among children. SCOPE, in partnership with a local organization, engages multiple stakeholders who plan and implement actions framed by a common evidence-based health message ('Live 5-2-1-0'). SCOPE's central team in Vancouver, BC facilitates alignment with provincial initiatives, knowledge translation and exchange (KTE) within and across communities, and the collection, analysis and reporting of shared data. OUTCOMES: Best practice processes that have emerged from SCOPE's experience align with the principles of CBPR and the five conditions of Collective Impact - a common agenda, mutually reinforcing action, continuous communication, a backbone organization and shared measurement. SCOPE has achieved sustainable practice change framed by a common agenda ('Live 5 2-1-0') leading to mutually reinforcing cross-sectoral action. CONCLUSION: A multi-pronged community-led childhood obesity prevention initiative can be achieved using CBPR principles and attending to the conditions for achieving collective impact. PMID- 26680436 TI - [An intervention research program (AAPRISS) to reduce social inequalities in health: methods and validation]. AB - OBJECTIVE: The AAPRISS intervention-research program (Apprendre et Agir Pour Reduire les Inegalites Sociales de Sante) aims to change prevention projects to improve the extent to which they take health inequalities into account. The goal is to assess a project's feasibility and its acceptability, from the viewpoint of the sponsors of the project in question, and to present its tools and potentially transferable elements. PARTICIPANTS: Five cancer-prevention projects focused on nutrition have been included in the AAPRISS program: two projects conducted in school, one community-health project conducted in a disadvantaged neighbourhood and two hospital therapeutic-education programes. For each one, a workgroup was created bringing together the project sponsors and their team as well as researchers from various disciplines. LOCATION: The study involves projects currently underway in the Midi- Pyrenees region of France. INTERVENTION: AAPRISS is based on the exchange of knowledge among project sponsors and researchers and the co-construction of the analysis, reorientations and the assessment of the prevention projects included in the program. The validation of the program and its feasibility from the project sponsors' point of view is based on a questionnaire and presentations carried out during a symposium that took place in May 2014 in Toulouse. RESULTS: Twelve key program functions have been described. They have been shown to be feasible and acceptable and concrete project modifications towards a better consideration of social inequalities of health (SIH) have been realized in most of the projects. Co-construction among the stakeholders raises many issues and difficulties that could have been overcome by the establishment of a relationship of trust between project sponsors and researchers. CONCLUSION: The complexity of the determinants leading to SIH calls for programs that revisit existing projects rather than a new intervention aimed at reducing them. PMID- 26680437 TI - Training the next generation of global health advocates through experiential education: A mixed-methods case study evaluation. AB - OBJECTIVES: This case study evaluates a global health education experience aimed at training the next generation of global health advocates. Demand and interest in global health among Canadian students is well documented, despite the difficulty in integrating meaningful experiences into curricula. METHODS: Global health advocacy was taught to 19 undergraduate students at McMaster University through an experiential education course, during which they developed a national advocacy campaign on global access to medicines. A quantitative survey and an analysis of social network dynamics were conducted, along with a qualitative analysis of written work and course evaluations. Data were interpreted through a thematic synthesis approach. RESULTS: Themes were identified related to students' learning outcomes, experience and class dynamics. The experiential education format helped students gain authentic, real-world experience in global health advocacy and leadership. The tangible implications for their course work was a key motivating factor. While experiential education is an effective tool for some learning outcomes, it is not suitable for all. As well, group dynamics and evaluation methods affect the learning environment. CONCLUSION: Real-world global health issues, public health practice and advocacy approaches can be effectively taught through experiential education, alongside skills like communication and professionalism. Students developed a nuanced understanding of many strategies, challenges and barriers that exist in advocating for public health ideas. These experiences are potentially empowering and confidence-building despite the heavy time commitment they require. Attention should be given to how such experiences are designed, as course dynamics and grading structure significantly influence students' experience. PMID- 26680438 TI - Electronic cigarettes: A comparison of national regulatory approaches. AB - E-cigarettes have been readily available to global markets since 2004. However, regulations have lagged behind popular use and availability. As policies emerging from national health agencies have an important role to play in shaping consumer health, we examined the existing and upcoming national regulations surrounding e cigarette availability and use in a convenience sample of English- and French speaking countries, including Canada, the United States, the United Kingdom, France, Australia and New Zealand. There is substantial international variation in regulatory policies and the extent to which these are enforced. Of the countries considered in this review, the US has regulations that remain the most permissive, whereas those in Canada and New Zealand are the most conservative. However, regulations in Canada, Australia and New Zealand are easily bypassed through Internet imports and lenient enforcement. European health agencies are paving the way for Member States to take appropriate steps to regulate e cigarettes according to their own jurisdictions. Currently, national regulations of e-cigarettes appear to be ill-defined in terms of shaping the future of e cigarette availability and use. National regulations should be strengthened to reflect the public health implications of e-cigarettes and to emphasize their difference from consumer products. PMID- 26680439 TI - Persons in correctional facilities in Canada: A key population for hepatitis C prevention and control. AB - About one in nine Canadians who are infected with hepatitis C spend time in a correctional facility each year. With high rates of current injection drug use and needle sharing, this population may account for a large proportion of new infections. Any national strategy to address hepatitis C should include a focus on persons in correctional facilities, and should build on existing evidence regarding primary, secondary and tertiary prevention. PMID- 26680440 TI - Contextualization of socio-culturally meaningful data. PMID- 26680441 TI - Collaborative opportunities for adolescents and young adults in the public health care decision-making process. PMID- 26680442 TI - Comparison of owner-reported behavioral characteristics among genetically clustered breeds of dog (Canis familiaris). AB - During the domestication process, dogs were selected for their suitability for multiple purposes, resulting in a variety of behavioral characteristics. In particular, the ancient group of breeds that is genetically closer to wolves may show different behavioral characteristics when compared to other breed groups. Here, we used questionnaire evaluations of dog behavior to investigate whether behavioral characteristics of dogs were different among genetically clustered breed groups. A standardized questionnaire, the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), was used, and breed group differences of privately-owned dogs from Japan (n = 2,951) and the United States (n = 10,389) were analyzed. Results indicated that dogs in the ancient and spitz breed group showed low attachment and attention-seeking behavior. This characteristic distinguished the ancient group from any other breed groups with presumed modern European origins, and may therefore, be an ancestral trait. PMID- 26680443 TI - A novel lipid transfer protein from the dill Anethum graveolens L.: isolation, structure, heterologous expression, and functional characteristics. AB - A novel lipid transfer protein, designated as Ag-LTP, was isolated from aerial parts of the dill Anethum graveolens L. Structural, antimicrobial, and lipid binding properties of the protein were studied. Complete amino acid sequence of Ag-LTP was determined. The protein has molecular mass of 9524.4 Da, consists of 93 amino acid residues including eight cysteines forming four disulfide bonds. The recombinant Ag-LTP was overexpressed in Escherichia coli and purified. NMR investigation shows that the Ag-LTP spatial structure contains four alpha helices, forming the internal hydrophobic cavity, and a long C-terminal tail. The measured volume of the Ag-LTP hydrophobic cavity is equal to ~800 A(3), which is much larger than those of other plant LTP1s. Ag-LTP has weak antifungal activity and unpronounced lipid binding specificity but effectively binds plant hormone jasmonic acid. Our results afford further molecular insight into biological functions of LTP in plants. PMID- 26680444 TI - Temperature oscillations near natural nuclear reactor cores and the potential for prebiotic oligomer synthesis. AB - Geologic settings capable of driving prebiotic oligomer synthesis reactions remain a relatively unexplored aspect of origins of life research. Natural nuclear reactors are an example of Precambrian energy sources that produced unique temperature fluctuations. Heat transfer models indicate that water moderated, convectively-cooled natural fission reactors in porous host rocks create temperature oscillations that resemble those employed in polymerase chain reaction (PCR) devices to artificially amplify oligonucleotides. This temperature profile is characterized by short-duration pulses up to 70-100 degrees C, followed by a sustained period of temperatures in the range of 30-70 degrees C, and finally a period of relaxation to ambient temperatures until the cycle is restarted by a fresh influx of pore water. For a given reactor configuration, temperature maxima and the time required to relax to ambient temperatures depend most strongly on the aggregate effect of host rock permeability in decreasing the thermal expansion and increasing the viscosity and evaporation temperature of the pore fluids. Once formed, fission-fueled reactors can sustain multi-kilowatt level power production for 10(5)-10(6) years, ensuring microenvironmental longevity and chemical output. The model outputs indicate that organic synthesis on young planetary bodies with a sizeable reservoir of fissile material can involve more sophisticated energy dissipation pathways than modern terrestrial analog settings alone would suggest. PMID- 26680445 TI - Formation of Hexamethylenetetramine (HMT) from HCHO and NH3--Relevance to Prebiotic Chemistry and B3LYP Consideration. AB - Despite its importance in the prebiotic and biochemical fields, a complete theoretical study of the formation of hexamethylenetetramine (HMT) starting from its precursors ammonia and formaldehyde has not received due considerations in the literature with regard to the thermodynamic feasibility of many of the mechanistically proposed intermediates in its formation. Most of the studies in this area have been mostly concerned with the initial steps of the reaction between formaldehyde and ammonia, while poor attention is dedicated to successive steps. In this article, different results from published literature were critically considered and the most probable hypothesis regarding the mechanism of HMT formation is discussed on the basis of B3LYP calculations of free energies. PMID- 26680446 TI - Complete mitochondrial genome sequence of Eurasian blackbird, Turdus merula (Aves: Turdidae). AB - The complete mitochondrial genome (mitogenome) sequence of Eurasian blackbird, Turdus merula was determined by shotgun sequencing. The total length of mitogenome is 16 730 bp, and contains 13 protein-coding genes, 22 tRNA genes, 2 ribosome RNA genes and 1 control region (D-loop). All the protein-coding genes in T. merula were distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes which were encoded on the L-strand. The gene order and contents in the T. merula mitogenome is identical to that found in typical vertebrates. The phylogenetic tree of T. merula and 13 other species belonging to order Passeriformes was built. The DNA data presented here will be useful to study the evolutionary relationships and genetic diversity of T. merula. PMID- 26680448 TI - Maximal Neighbor Similarity Reveals Real Communities in Networks. AB - An important problem in the analysis of network data is the detection of groups of densely interconnected nodes also called modules or communities. Community structure reveals functions and organizations of networks. Currently used algorithms for community detection in large-scale real-world networks are computationally expensive or require a priori information such as the number or sizes of communities or are not able to give the same resulting partition in multiple runs. In this paper we investigate a simple and fast algorithm that uses the network structure alone and requires neither optimization of pre-defined objective function nor information about number of communities. We propose a bottom up community detection algorithm in which starting from communities consisting of adjacent pairs of nodes and their maximal similar neighbors we find real communities. We show that the overall advantage of the proposed algorithm compared to the other community detection algorithms is its simple nature, low computational cost and its very high accuracy in detection communities of different sizes also in networks with blurred modularity structure consisting of poorly separated communities. All communities identified by the proposed method for facebook network and E-Coli transcriptional regulatory network have strong structural and functional coherence. PMID- 26680447 TI - Suicidal behavior-related hospitalizations among pregnant women in the USA, 2006 2012. AB - Suicide is one of the leading causes of maternal mortality in many countries, but little is known about the epidemiology of suicide and suicidal behavior among pregnant women in the USA. We sought to examine trends and provide nationally representative estimates for suicidal behavior (including suicidal ideation and suicide and self-inflicted injury) among pregnant women from 2006 to 2012 in the USA. Pregnant women aged 12-55 years were identified through pregnancy- and delivery-related hospitalization records from the National (Nationwide) Inpatient Sample. Suicidal behavior was identified by the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Annual, nationwide estimates and trends were determined using discharge and hospital weights. The prevalence of suicidal ideation more than doubled from 2006 to 2012 (47.5 to 115.0 per 100,000 pregnancy- and delivery-related hospitalizations), whereas the prevalence of suicide and self-inflicted injury remained stable. Nearly 10 % of suicidal behavior occurred in the 12-18-year group, showing the highest prevalence per 100,000 pregnancy- and delivery-related hospitalizations (158.8 in 2006 and 308.7 in 2012) over the study period. For suicidal ideation, blacks had higher prevalence than whites; women in the lowest income quartile had the highest prevalence. Although the prevalence of suicidal behavior was higher among hospitalizations with depression diagnoses, more than 30 % of hospitalizations were for suicidal behavior without depression diagnoses. Our findings highlight the increasing burden and racial differences in suicidal ideation among US pregnant women. Targeted suicide prevention efforts are needed for high-risk pregnant women including teens, blacks, and low-income women. PMID- 26680449 TI - Early Experience of Endovascular Repair of Post-dissection Aneurysms Involving the Thoraco-abdominal Aorta and the Arch. AB - OBJECTIVES: Outcomes are reported in management of post-dissection aneurysms involving the aortic arch and/or thoraco-abdominal segment (TAAA) treated with fenestrated and branched (complex) endografts. METHODS: This report includes all patients with chronic post-dissection aneurysms >55 mm in diameter, deemed unfit for open surgery, treated using complex endografts between October 2011 and March 2015. When appropriate, staged management strategies including left subclavian artery revascularization, thoracic endografting, dissection flap fenestration or tear enlargement, and other endovascular procedures were performed at least 3 weeks prior to definitive complex endovascular repair. The following outcome data were collected prospectively at discharge, 12 months and annually thereafter: technical success, endoleaks, target vessel patency, false lumen patency, aneurysm diameter, major and minor complications, re-interventions, and mortality. RESULTS: The cohort comprised 23 patients with a median age of 65 years. Staged procedures were performed in 14 patients (61%). Seven patients with dissections involving the arch were treated with inner branched endografts, and 16 TAAA patients were treated with fenestrated or branched endografts. The technical success rate was 71% following arch repair and 100% following TAAA repair. During early follow up, one of the arch group patients died and one in the TAAA group suffered spinal cord ischemia. The median follow up was 12 months (range 3-48), during which time one patient died of causes unrelated to aneurysm or treatment. Two early re-interventions were performed in the arch group to correct access vessel complications and there were a further two late re interventions in the TAAA group to treat endoleaks. All target vessels (n = 72) remained patent. CONCLUSIONS: This experience indicates that complex endovascular repair of post-dissection aneurysms is a viable alternative to open repair in patients deemed unfit for open surgery. There are insufficient data to allow comparison with the outcome of open surgery in anatomically similar, but fit, patients. PMID- 26680450 TI - Commentary on 'Comparison of the Antimicrobial Properties of Silver Impregnated Vascular Grafts with and without Triclosan'. PMID- 26680451 TI - Comparison of the Antimicrobial Properties of Silver Impregnated Vascular Grafts with and without Triclosan. AB - OBJECTIVES: The aim was to compare the antimicrobial efficacy of the silver impregnated collagen coated polyester vascular graft (IGS) with an identical graft combining silver and triclosan (IGSy). METHODS: This was an in vitro study. A non-antimicrobial collagen polyester vascular graft served as control (IG). The IG, IGS, and IGSy grafts were contaminated separately with inoculates of each of the following micro-organisms: Staphylococcus epidermidis (SE), methicillin resistant Staphylococcus aureus (MRSA), and Escherichia coli producing extended spectrum beta-lactamase (ESBL-EC) or Candida albicans (CA). MRSA, ESBL-EC, and CA were obtained from retrieved infected grafts. The in vitro antimicrobial efficacies of the contaminated grafts were evaluated by time to kill assays over a 24 hour period in accordance with CLSI Guideline M26-A. All assays were repeated six times. Bacterial survival numbers were obtained at 1, 4, 8, and 24 hours using a standard plate count procedure. Bactericidal activity was defined as a 3 log10 reduction factor (logRF). To calculate the overall difference in the mean log10 CFU/mL within 24 hours, a one way ANOVA with a Bonferroni correction was calculated separately for each graft. RESULTS: The IG graft showed an increase in the number of viable organisms for the four strains tested. IGSy offered better antimicrobial properties than IGS for both ESBL-EC and MRSA, since only the IGSy graft achieved > 3 logRF and fulfilled the standard criteria for bactericidal activity at 24 hours with 3.78 and 4.08 logRF, respectively. For samples inoculated with SE and CA, both antimicrobial grafts achieved 24 hour bactericidal activity with > 3 logRF. However, for CA the one-way ANOVA analysis demonstrated that the IGSy graft performed differently in terms of speed of antimicrobial action, appearing more active as early as 4 hours following inoculation (p = .007). CONCLUSION: In the in vitro conditions, the Synergy vascular graft combining silver with triclosan demonstrated better short-term antimicrobial activity than the silver graft for all micro-organisms tested. PMID- 26680453 TI - Response to 'RE: How Should I Treat a Patient with a Tandem Carotid Artery Atherosclerotic Stenosis Involving the Internal Carotid Artery and the Innominate/Proximal Common Carotid Artery?'. PMID- 26680452 TI - Ruptured Pancreaticoduodenal Artery Aneurysms Associated with Celiac Stenosis Caused by the Median Arcuate Ligament: A Poorly Known Etiology of Acute Abdominal Pain. AB - OBJECTIVE/BACKGROUND: Pancreaticoduodenal artery (PDA) aneurysm is a rare but clinically important form of vascular disease. A small proportion of these aneurysms are caused by compression of the artery by the median arcuate ligament (MAL). The objective of the study was to establish whether it is feasible and effective to treat ruptured PDA aneurysms without treating the celiac stenosis caused by the MAL. METHODS: From January 2007 to November 2014, 10 patients were included. Standard embolization or surgical procedures were used to treat the ruptured aneurysms, but the celiac stenosis itself was not treated. The primary end point was the feasibility and efficacy of embolization for the treatment of ruptured PDA aneurysms. The secondary end points included clinical data, imaging findings, the success rate of embolization and the outcome during follow up. RESULTS: All patients presented with acute, non-specific epigastric pain with nausea. An abdominal computed tomography scan revealed peri-pancreatic hematoma in all cases, and PDA aneurysms were visible in six patients. The aneurysms ranged from 2 mm to 10 mm in diameter and were variously located on the anterior PDA (n = 1), the posterior PDA (n = 3), and the branch of the dorsal pancreatic artery (n = 6). Surgery was performed in two cases (with one death). Embolization was successful in the other eight cases. The median length of hospital stay was 10 days (range 8-25 days). Over a median follow up period of 11 months (range 5 48 months), none of the PDA aneurysms recurred. CONCLUSION: Rupture of a PDA aneurysm caused by the MAL should always be considered in the differential diagnosis of acute abdominal pain, because the condition requires specific management. Embolization is safe and has a high success rate. Surgery should only be performed when embolization fails. PMID- 26680456 TI - Hemorrhagic Pituitary Adenoma versus Rathke Cleft Cyst: A Frequent Dilemma. PMID- 26680455 TI - Metagenome from a Spirulina digesting biogas reactor: analysis via binning of contigs and classification of short reads. AB - BACKGROUND: Anaerobic digestion is a biological process in which a consortium of microorganisms transforms a complex substrate into methane and carbon dioxide. A good understanding of the interactions between the populations that form this consortium can contribute to a successful anaerobic digestion of the substrate. In this study we combine the analysis of the biogas production in a laboratory anaerobic digester fed with the microalgae Spirulina, a protein rich substrate, with the analysis of the metagenome of the consortium responsible for digestion, obtained by high-throughput DNA sequencing. The obtained metagenome was also compared with a metagenome from a full scale biogas plant fed with cellulose rich material. RESULTS: The optimal organic loading rate for the anaerobic digestion of Spirulina was determined to be 4.0 g Spirulina L(-1) day(-1) with a specific biogas production of 350 mL biogas g Spirulina (-1) with a methane content of 68 %. Firmicutes dominated the microbial consortium at 38 % abundance followed by Bacteroidetes, Chloroflexi and Thermotogae. Euryarchaeota represented 3.5 % of the total abundance. The most abundant organism (14.9 %) was related to Tissierella, a bacterium known to use proteinaceous substrates for growth. Methanomicrobiales and Methanosarcinales dominated the archaeal community. Compared to the full scale cellulose-fed digesters, Pfam domains related to protein degradation were more frequently detected and Pfam domains related to cellulose degradation were less frequent in our sample. CONCLUSIONS: The results presented in this study suggest that Spirulina is a suitable substrate for the production of biogas. The proteinaceous substrate appeared to have a selective impact on the bacterial community that performed anaerobic digestion. A direct influence of the substrate on the selection of specific methanogenic populations was not observed. PMID- 26680457 TI - Reply. PMID- 26680454 TI - The genomic and transcriptomic landscape of anaplastic thyroid cancer: implications for therapy. AB - BACKGROUND: Anaplastic thyroid carcinoma is the most undifferentiated form of thyroid cancer and one of the deadliest of all adult solid malignancies. Here we report the first genomic and transcriptomic profile of anaplastic thyroid cancer including those of several unique cell lines and outline novel potential drivers of malignancy and targets of therapy. METHODS: We describe whole genomic and transcriptomic profiles of 1 primary anaplastic thyroid tumor and 3 authenticated cell lines. Those profiles augmented by the transcriptomes of 4 additional and unique cell lines were compared to 58 pairs of papillary thyroid carcinoma and matched normal tissue transcriptomes from The Cancer Genome Atlas study. RESULTS: The most prevalent mutations were those of TP53 and BRAF; repeated alterations of the epigenetic machinery such as frame-shift deletions of HDAC10 and EP300, loss of SMARCA2 and fusions of MECP2, BCL11A and SS18 were observed. Sequence data displayed aneuploidy and large regions of copy loss and gain in all genomes. Common regions of gain were however evident encompassing chromosomes 5p and 20q. We found novel anaplastic gene fusions including MKRN1-BRAF, FGFR2-OGDH and SS18 SLC5A11, all expressed in-frame fusions involving a known proto-oncogene. Comparison of the anaplastic thyroid cancer expression datasets with the papillary thyroid cancer and normal thyroid tissue transcriptomes suggested several known drug targets such as FGFRs, VEGFRs, KIT and RET to have lower expression levels in anaplastic specimens compared with both papillary thyroid cancers and normal tissues, confirming the observed lack of response to therapies targeting these pathways. Further integrative data analysis identified the mTOR signaling pathway as a potential therapeutic target in this disease. CONCLUSIONS: Anaplastic thyroid carcinoma possessed heterogeneous and unique profiles revealing the significance of detailed molecular profiling of individual tumors and the treatment of each as a unique entity; the cell line sequence data promises to facilitate the more accurate and intentional drug screening studies for anaplastic thyroid cancer. PMID- 26680458 TI - Reply. PMID- 26680459 TI - Cortical Cerebral Blood Flow, Oxygen Extraction Fraction, and Metabolic Rate in Patients with Middle Cerebral Artery Stenosis or Acute Stroke. AB - BACKGROUND AND PURPOSE: With the advances of magnetic resonance technology, the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen can be measured in MRI. Our aim was to measure the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen use in patients with different severities of middle cerebral artery stenosis or acute stroke by using the arterial spin labeling and susceptibility-weighted imaging techniques. MATERIALS AND METHODS: Fifty-seven patients with MCA stenosis or acute stroke were recruited and classified into 4 groups: mild MCA stenosis (group 1), severe MCA stenosis (group 2), occluded MCA (group 3), and acute stroke (group 4). Arterial spin-labeling and SWI sequences were used to acquire CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen. RESULTS: The oxygen extraction fraction in hemispheres with mild MCA stenosis (group 1) was remarkably higher than that in the contralateral hemisphere. In addition, hemispheres with severe MCA stenosis (group 2) had significantly lower CBF and a significantly higher oxygen extraction fraction than the contralateral hemisphere. Hemispheres with occluded MCA (group 3) or acute stroke (group 4) had a significantly lower CBF and cerebral metabolic rate of oxygen and a significantly higher oxygen extraction fraction than the contralateral hemisphere. CONCLUSIONS: The oxygen extraction fraction gradually increased in groups 1-3. When this offset a decrease in CBF, the cerebral metabolic rate of oxygen remained at a normal level. An occluded MCA led to reduction in both the CBF and cerebral metabolic rate of oxygen. Moreover, the oxygen extraction fraction and cerebral metabolic rate of oxygen significantly increased and decreased, respectively, in the occluded MCA region during acute stroke. PMID- 26680460 TI - Reply. PMID- 26680461 TI - Stents for Idiopathic Intracranial Hypertension: Meta-Analyzed, Hypo-Analyzed, and In Need of a Trial. PMID- 26680462 TI - In Reply to Antiplatelet Therapy Prior to Temporary Stent-Assisted Coiling. PMID- 26680463 TI - Quantitative Assessment of Neovascularization after Indirect Bypass Surgery: Color-Coded Digital Subtraction Angiography in Pediatric Moyamoya Disease. AB - BACKGROUND AND PURPOSE: For the postoperative follow-up in pediatric patients with Moyamoya disease, it is essential to evaluate the degree of neovascularization status. Our aim was to quantitatively assess the neovascularization status after bypass surgery in pediatric Moyamoya disease by using color-coded digital subtraction angiography. MATERIALS AND METHODS: Time attenuation intensity curves were generated at ROIs corresponding to surgical flap sites from color-coded DSA images of the common carotid artery, internal carotid artery, and external carotid artery angiograms obtained pre- and postoperatively in 32 children with Moyamoya disease. Time-to-peak and area under the curve values were obtained. Postoperative changes in adjusted time-to-peak (DeltaTTP) and ratios of adjusted area under the curve changes (DeltaAUC ratio) of common carotid artery, ICA, and external carotid artery angiograms were compared across clinical and angiographic outcome groups. To analyze diagnostic performance, we categorized clinical outcomes into favorable and unfavorable groups. RESULTS: The DeltaTTP at the common carotid artery increased among clinical and angiographic outcomes, in that order, with significant differences (P = .003 and .005, respectively). The DeltaAUC ratio at the common carotid artery and external carotid artery also increased, in that order, among clinical and angiographic outcomes with a significant difference (all, P = .000). The DeltaAUC ratio of ICA showed no significant difference among clinical and angiographic outcomes (P = .418 and .424, respectively). The DeltaTTP for the common carotid artery of >1.27 seconds and the DeltaAUC ratio of >33.5% for the common carotid artery and 504% for the external carotid artery are revealed as optimal cutoff values between favorable and unfavorable groups. CONCLUSIONS: Postoperative changes in quantitative values obtained with color-coded DSA software showed a significant correlation with outcome scores and can be used as objective parameters for predicting the outcome in pediatric Moyamoya disease, with an additional cutoff value calculated through the receiver operating characteristic curve. PMID- 26680465 TI - Erratum. PMID- 26680464 TI - High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis. AB - BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. MATERIALS AND METHODS: Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. RESULTS: Ultra high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). CONCLUSIONS: The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. PMID- 26680466 TI - Quantitative Susceptibility Mapping Suggests Altered Brain Iron in Premanifest Huntington Disease. AB - BACKGROUND AND PURPOSE: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression. MATERIALS AND METHODS: Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures. RESULTS: Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores. CONCLUSIONS: The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease. PMID- 26680468 TI - Erratum for Pastrana et al., BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism. PMID- 26680467 TI - Wing Shape Variation in the Taxonomic Recognition of Species of Diachlorus Osten Sacken (Diptera: Tabanidae) from Colombia. AB - We evaluated the directional asymmetry between right and left wings and quantified the intraspecific and interspecific variation of the wing shape of 601 specimens of the genus Diachlorus to determine to what extent the geometrical variation discriminates six species distributed in six protected areas of Colombia. Geometric analyses were performed, integrating Procrustes methods, principal component analyses, cluster analyses, linear and quadratic discriminant analyses, and evaluations of shape changes. In Diachlorus, left and right wings did not present significant asymmetry but a geometrical analysis was allowed for species identification and, in some cases, the origin of the specimens using the variation of wing shape; the best-assigned species was Diachlorus leticia Wilkerson & Fairchild, while the worst was Diachlorus jobbinsi Fairchild, which also had the highest intraspecific variation, while Diachlorus fuscistigma Lutz had the lowest variation. Diachlorus fuscistigma and Diachlorus leucotibialis Wilkerson & Fairchild were the most similar species, while D. leucotibialis and Diachlorus nuneztovari Fairchild & Ortiz were the most disimilar. The specimens with the most different wing shape belonged to Choco (especially those of D. jobbinsi), the geographically farthest area from the others in the study; however, no correlation was observed between geometric and geographical distances. Linear discriminants were better than nonlinear (quadratic) discriminant analyses in predicting species membership, but the opposite was true for predicting area membership. Based on our data, we hypothesized that other species of Diachlorus could also be discriminated using geometric morphometry of the wing shape. PMID- 26680470 TI - Overall Water Splitting on the Transition-Metal Oxynitride Photocatalyst LaMg1/3Ta2/3O2N over a Large Portion of the Visible-Light Spectrum. AB - One of the main targets of studies on water splitting photocatalysts is to develop semiconductor materials with narrower bandgaps capable of overall water splitting for efficient harvesting of solar energy. A series of transition-metal oxynitrides, LaMgx Ta1-xO1+3xN2-3x(x >= 1/3), with a complex perovskite structure was reported as the first example of overall water splitting operable at up to 600 nm. The photocatalytic behavior of LaMg1/3Ta2/3O2N was investigated in detail in order to optimize photocatalyst preparation and water-splitting activity. Various attempts exploring photocatalyst preparation steps, that is, cocatalyst selection, coating material and method, and synthesis method for the oxide precursor, revealed photocatalyst structures necessary for achieving overall water splitting. Careful examination of photocatalyst preparation procedures likely enhanced the quality of the produced photocatalyst, leading to a more homogeneous coating quality and semiconductor particles with fewer defects. Thus, the photocatalytic activity for water splitting on LaMg1/3Ta2/3O2N was largely enhanced. PMID- 26680471 TI - Vitamin D in anxiety and affective disorders. AB - Reduced levels of vitamin or its metabolites have been reported in various psychiatric disorders. Insufficient levels of vitamin D in depressive patients have been confirmed by many authors, but there have been conflicting results in subjects with anxiety disorders. In the present cross-sectional study, levels of calcidiol were determined in groups of depressive men and women and in men and women with anxiety disorders and compared with age matched controls. Significantly lower levels of calcidiol were found in men and women with depression as well as in age matched patients with anxiety disorders. PMID- 26680472 TI - Obesity and infection: reciprocal causality. AB - Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections. PMID- 26680473 TI - Steroid hormones related to 11beta-hydroxysteroid dehydrogenase type 1 in treated obesity. AB - The local concentration of glucocorticoids is intensively regulated by 11beta hydroxysteroid dehydrogenase type 1 (11beta-HSD 1). Human 11beta-HSD 1 also reversibly catalyzes the inter-conversion of 7alpha-hydroxy- and 7beta-hydroxy dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7beta-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7alpha-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11beta HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11beta-HSD 1 in the liver. PMID- 26680474 TI - Gestational diabetes - metabolic risks of adult women with respect to birth weight. AB - Metabolic disorders such as obesity, insulin resistance and other components of metabolic syndrome (MetS) are connected with birth weight. Low and high birth weight is associated with a higher risk of developing type 2 diabetes mellitus, the mechanism is not clear. In this study, we evaluated the association between birth weight and anthropometric as well as biochemical components of MetS in women with a history of gestational diabetes mellitus (GDM) in comparison with control women. In part of the GDM group, we re-evaluated metabolic changes over 5 8 years. Anthropometry, blood pressure, glucose metabolism during the 3-h oGTT, lipid profile, uric acid, thyroid hormones, and liver enzymes were assessed. From the analyzed components of MetS in adult women we proved the association of low birth weight (birth weight <25th percentile) with glucose processing, in particular among women with a history of GDM. Low birth weight GDM women revealed significantly higher postchallenge insulin secretion and lower peripheral insulin sensitivity. Re-examinations indicate this association persists long after delivery. PMID- 26680475 TI - Levels of adipokines and some steroids during the menstrual cycle. AB - The cyclical effects of hormones during the menstrual cycle (MC) are not just responsible for driving ovulation, but also have significant influence on dietary intake and appetite, as well as psychological and behavioral changes. The aim of our study was to describe changes and relationships between the MC and selected steroids, adipokines and food intake-related hormones. Twenty-seven women with regular menstrual cycles were included in the study, and their hormonal spectrum was measured in regular intervals starting from the first day of their cycle. Classical changes in gonadotropins, estrogens and progesterone during the menstrual cycle are accompanied by less striking but significant changes in 17 hydroxyprogesterone and testosterone. No significant changes show dehydroepiandrosterone and its 7-oxygenated metabolites. Adipokines show a tendency to increase during ovulation, while ghrelin and resistin decrease. There is also a remarkable association of sex hormone-binding globulin on the day of the cycle. Our results demonstrate that changes to adipokines during the menstrual cycle are not substantial, but nonetheless can play a role in the changes of food intake described in the literature. Precise descriptions of physiological changes in healthy women are important in helping us understand the significance of the changes accompanying various pathological states. PMID- 26680476 TI - Fatty acid composition of adipose tissue triglycerides in obese diabetic women after bariatric surgery: a 2-year follow up. AB - Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n 3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used. PMID- 26680477 TI - Association of plasma lipids fatty acid composition with metabolic profile of Czech adolescents. AB - Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesity-associated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels. PMID- 26680478 TI - Fat mass and obesity associated gene variants are associated with increased growth hormone levels and affect glucose and lipid metabolism in lean women. AB - First intron variability of the fat mass and obesity associated gene (FTO) has strong impact on adiposity. We focused on lean women carrying the most "obesity risk" haplotype to study their anthropometric parameters and hormonal and metabolic profile. Genotype-phenotype correlation was performed in a group of 172 lean women (body mass index (BMI) >/=18.5 and 25 kg/m(2); age 26.8+/-7.26 years), 77 of them used hormonal contraceptives. Even in lean women the association of the risk haplotype CAGA with BMI was confirmed but it did not influence the anthropometric indices of body composition. CAGA carriers compared to non carriers had significantly higher both fasting (p=0.016) and post glucose load (p<0.001) levels of growth hormone (GH), significantly higher glucose, insulin and C-peptide levels in the late phase of oGTT and lower fasting concentration of total cholesterol and LDL-cholesterol. Administration of hormonal contraceptives further increased observed hormonal and metabolic effects in CAGA carriers. We conclude that higher levels of GH in lean women carrying the FTO "obesity risk" haplotype could protect them from the development of obesity. The relation between the FTO gene variability and GH secretion has to be elucidated. This is the first study demonstrating the interaction of FTO genotype with hormonal contraception. PMID- 26680479 TI - Metabolic and hormonal consequencies of the "obesity risk" MC4R variant (rs12970134) in Czech women. AB - Although the mutations in MC4R gene became known as the most common genetic cause of human obesity, the effect of rs12970134 A/G near MC4R gene on insulin resistance has been described. The aim of this study was to determine the effect of rs12970134 on obesity, hormone levels, and glucose metabolism in a cohort of women varying in glucose tolerance: 850 normoglycemic women, 423 diagnosed with polycystic ovary syndrome (PCOS), 402 gestational diabetics (GDM), and 250 type 2 diabetic (T2D) women. We did not confirm the explicit effect of rs12970134 on obesity. However, the influence of the A-allele on body adiposity index was observed in a cohort of women diagnosed with PCOS. In normoglycemic women, the A allele carriership was associated with lower fasting levels of glucose, insulin, C-peptide, and index of insulin resistance. Furthermore, higher levels of growth hormone, leptin and SHBG, and lower levels of fT3, testosterone, and androstenedione were recorded in normoglycemic A-allele carriers. In conclusion, the study presents the evidence of the impact of rs12970134 on complex hypothalamic regulations. PMID- 26680480 TI - Association of adenovirus 36 infection with obesity-related gene variants in adolescents. AB - Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0 17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. non carriers (chi(2)=6.59, p=0.010; chi(2)=7.56, p=0.023 and chi(2)=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (chi(2)=5.09, p=0.024; chi(2)=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (chi(2)=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection. PMID- 26680481 TI - The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy. AB - Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women. PMID- 26680482 TI - The steroid spectrum during and after quitting smoking. AB - Addiction to tobacco results in an imbalance of endocrine homeostasis in both sexes. This can also have impacts on fertility problems. The male reproductive system is less susceptible than that of females, with a worsening spermiogram in smokers, the most cited effect in the literature. However, the literature is inconsistent as to the effects of smoking on steroid hormone levels in men, and there is very little data on the effects of quitting smoking in men. In this study we followed 76 men before quitting smoking, and then after 6, 12, and 24 weeks and 1 year of abstinence. We measured basic anthropomorphic data and steroid hormone levels along with steroid neuroactive metabolites using GC-MS. We demonstrate lower androgen levels in men who smoke, and these changes worsened after quitting smoking. There was a drop in SHBG already in the first week of non smoking, and levels continued to remain low. Male smokers have lower androgen levels compared to non-smokers. The lower the initial level of androgen, the lower the likelihood of success in quitting smoking. Changes in steroid hormones proved to be a promising marker for the prediction of success in quitting smoking. PMID- 26680483 TI - Daily profiles of steroid hormones and their metabolites related to food intake. AB - The aim of this study was to look for changes in the daily profile of steroid hormones after standardized food intake. Eight young women not taking contraceptives were followed from 5:30 a.m. till 9:30 p.m. before and 1 and 2 h after eating breakfast, snack, lunch, the second snack and dinner. The differences in steroid levels before and after meals were evaluated. As expected, glucose, C-peptide and ghrelin levels changed postprandially. The steroid hormones cortisol, progesterone, pregnenolone and dehydroepiandrosterone showed a decrease after main meals, whereas testosterone and dihydrotestosterone showed no significant dependence on food intake. Estrogen levels did not exhibit a significant nycthemeral rhythm, but estradiol decreased after main meals. In our study the known nycthemeral rhythm of LH, FSH, cortisol, progesterone and pregnenolone after food intake were confirmed, but significant changes after meals were also observed in the levels of cortisol, dehydroepiandrosterone, estradiol and SHBG. PMID- 26680484 TI - Steroid hormones and homocysteine in the outcome of patients with normal pressure hydrocephalus. AB - Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7alpha hydroxy-DHEA, 7beta-hydroxy-DHEA, 7-oxo-DHEA, 16alpha-hydroxy-DHEA (all LC MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16alpha-hydroxy-DHEA and plasma DHEAS, 7beta-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia. PMID- 26680485 TI - Response of cortisol metabolites in the insulin tolerance test and Synacthen tests. AB - Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test. PMID- 26680486 TI - Increased serum levels of C21 steroids in female patients with multiple sclerosis. AB - Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 age-corresponding female controls with the use of gas chromatography - mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A gamma-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3beta,7alpha,17beta-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity. PMID- 26680487 TI - DHEA, DHEAS and prolactin correlate with glucose control parameters in women of fertile age with type-1 diabetes mellitus. AB - The aim of our work was to provide data from women of fertile age with type 1 diabetes mellitus about the endogenous androgens and on their relations to the parameters of diabetes control. Forty-two women were examined, they did not use contraceptives for at least three months prior to the examination. A multivariate regression analysis showed that the daily insulin dose, the fasting glycemia and the HbA1c values and patient's age correlated negatively with dehydroepiandrosterone sulfate, dehydroepiandrosterone and prolactin levels. The testosterone/dehydroepiandrosterone sulfate ratio correlated positively with daily insulin dose and patient's age. In contrast to adrenal androgens the values of other hormones, including total and free testosterone, androstenedione, dihydrotestosterone, estradiol, LH, FSH, 17-OH-P, progesterone and cortisol revealed no significant correlation. To conclude, significant relations between the glucose control parameters and the adrenal androgens and prolactin were demonstrated. These relationships should be considered as an important factor influencing diabetes control so the additional cardiovascular risk in women with DM1. PMID- 26680488 TI - How hormones influence composition and physiological function of the brain-blood barrier. AB - Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves. PMID- 26680489 TI - Reduced sulfotransferase SULT2A1 activity in patients with Alzheimer's disease. AB - Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5alpha-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD. PMID- 26680490 TI - The steroid metabolome in men with mood and anxiety disorders. AB - The mood and behavior of individuals result from an orchestra of many factors. Among them steroids play an important role; however, only several common hormones have been investigated in this respect. It has been demonstrated that some steroid metabolites long considered merely the products of steroid hormone metabolism in fact possess considerable activity in the CNS. For this reason we studied the steroid metabolome including 50 analytes in 20 men with depression, 20 men with anxiety and 30 healthy controls. Significant differences were found not only between controls and men with either depression or anxiety, but also between men with depression and anxiety. Particularly striking were those steroids until now not generally associated with depression or anxiety, namely conjugated steroid forms, especially sulfates. PMID- 26680491 TI - The impact of selected cytokines in the follow-up of normal pressure hydrocephalus. AB - Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion. PMID- 26680492 TI - Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract. AB - Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori. PMID- 26680493 TI - Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility. AB - The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration. PMID- 26680494 TI - Deconjugated urinary metanephrine, normetanephrine and 3-methoxytyramine in laboratory diagnosis of pheochromocytoma and paraganglioma. AB - This work discusses the clinical performance of deconjugated metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) determined in the basal first morning urine using a chromatographic method with electrochemical detection for the clinical diagnosis of pheochromocytoma (PHEO) and paraganglioma (PGL). Urine samples were collected from 44 patients (36 with PHEO, 8 with PGL) aged 54+/-17 (20-78) years (22 females, 22 males). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The control group consisted of 34 PHEO/PGL patients more than 4 months after adrenal gland surgery. All subjects in the control group were without a diagnosis of PHEO or PGL. Clinical sensitivity was 55 % for MN, 64 % for NMN, 80 % for combination of both MN and NMN, and only 23 % for 3TM. Clinical specificity calculated from the control group was 93 % for MN, 95 % for NMN, 95 % for the combination MN and NMN, and 97 % for 3TM. Cut-off values for deconjugated metanephrines in the basal urine were 310 (MN), 690 (NMN) and 250 microg/l (3MT). Chromatographic determination of deconjugated urinary metanephrines, which is simple without the necessity of special laboratory material, can serve for the screening of PHEO or PGL patients. Urine NMN and 3MT exerts an association to malignity, and all markers are associated with tumor mass. However, the principal laboratory diagnosis of PHEO or PGL must be based on plasma-free metanephrines and plasma chromogranin A with better performance in the laboratory diagnosis of PHEO or PGL. PMID- 26680496 TI - Corrigendum. PMID- 26680495 TI - Vitamin D and thyroid diseases. AB - In this review we summarize recent opinions on the possible role of vitamin D in the risk of thyroid diseases development. It may be concluded from the available data that vitamin D deficiency, particularly levels below 12.5 ng/ml should be considered as an additional, but important risk factor for development of thyroid autoimmunity, both chronic autoimmune thyroiditis and Graves' disease. A higher risk of Graves' disease development is also associated with several polymorphisms in the gene encoding for vitamin D binding protein and for the specific receptor of active form of vitamin D - 1,25-(OH)(2)D(3) in the respective target cells. Important for development of thyroid cancer appeared polymorphisms of genes encoding for vitamin D receptors and of genes encoding for the participating hydroxylating enzymes in thyroid tissue, leading to a diminished local 1,25 (OH)(2)D(3) formation capacity with following alteration of antiproliferatory, antiapoptotic and prodifferentiating efficacy of the latter. Whether supplementation with high doses of vitamin D or its analogues possesses preventive or therapeutic effect is an object of intensive studies. PMID- 26680497 TI - Daptomycin in peritoneal dialysis, intraperitoneal or intravenous. PMID- 26680498 TI - Utility of a predictive model for chronic kidney disease in level 1 medical care. PMID- 26680499 TI - Corrigendum: Crystal structure of caspase recruiting domain (CARD) of apoptosis repressor with CARD (ARC) and its implication in inhibition of apoptosis. PMID- 26680500 TI - Graphene oxide/PEDOT:PSS composite hole transport layer for efficient and stable planar heterojunction perovskite solar cells. AB - We investigated a graphene oxide (GO)/poly(3,4 ethylenedioxythiophene):poly(styrene sulfonate) ( PEDOT: PSS) composite as a promising candidate for the practical application of a 2-D carbonaceous hole transport layer (HTL) to planar heterojunction perovskite solar cells (PeSCs) consisting of a transparent electrode/HTL/perovskite/fullerene/metal electrode. Both the insulating properties of GO and the non-uniform coating of the transparent electrode with GO cause the poor morphology of perovskite induced low power conversion efficiency (PCE) of 6.4%. On the other hand, PeSCs with a GO/PEDOT:PSS composite HTL, exhibited a higher PCE of 9.7% than that of a device fabricated with conventional PEDOT: PSS showing a PCE of 8.2%. The higher performance is attributed to the decreased series resistance (RS) and increased shunt resistance (RSh). The well-matched work-function between GO (4.9 eV) and PEDOT: PSS (5.1 eV) probably results in more efficient charge transport and an overall decrease in RS. The existence of GO with a large bandgap of ~3.6 eV might induce the effective blocking of electrons, leading to an increase of RSh. Moreover, improvement in the long-term stability under atmospheric conditions was observed. PMID- 26680502 TI - High Altitude and Acute Mountain Sickness and Changes in Circulating Endothelin 1, Interleukin-6, and Interleukin-17a. AB - INTRODUCTION: Hypoxia induces an inflammatory response, which is enhanced by exercise. High altitude (HA) leads to endothelial activation and may be proinflammatory. The relationship between endothelial activation, inflammation, and acute mountain sickness (AMS) and its severity has never been examined. METHODS: Forty-eight trekkers were studied during a progressive trek at 3833, 4450, and 5129 m at rest postascent (exercise), and then again at rest 24 hours later. Twenty of the subjects were also tested at rest pre- and postexercise at sea level (SL) at 6 weeks preascent. We examined plasma levels of the interleukin 6 (IL-6), 17a (IL-17a), and endothelin-1 (ET-1) along with oxygen saturation (SpO2) and Lake Louise scores (LLS). RESULTS: ET-1 (5.7 +/- 2.1 vs. 4.3 +/- 1.9 pg/mL; p < 0.001), IL-6 (3.3 +/- 3.3 vs. 2.4 +/- 2.3 pg/mL; p = 0.007), and IL 17a (1.3 +/- 3.0 vs. 0.46 +/- 0.4 pg/mL; p < 0.001) were all overall significantly higher at HA versus SL. There was a paired increase in ET-1 and IL 6 with exercise versus rest at SL, 3833, 4450, and 5129 m (p < 0.05). There was a negative correlation between LLS and SpO2 (r = -0.32; 95% confidence interval [CI] -0.21 to -0.42; p < 0.001) and a positive correlation between LLS and IL-6 (r = 0.16; 0.0-0.27; p = 0.007) and ET-1 levels (r = 0.29; 0.18-0.39; p < 0.001. Altitude, ET-1, IL-6, and SpO2 were all univariate predictors of AMS. On multivariate analysis, ET-1 (p = 0.002) and reducing SpO2 (p = 0.02) remained as the only independent predictors (overall r(2) = 0.16; p < 0.001) of AMS. ET-1 (p = 03) and SpO2 were (p = 0.01) also independent predictors of severe AMS (overall r(2) = 0.19; p < 0.001). CONCLUSIONS: HA leads to endothelial activation and an inflammatory response. The rise in ET-1 and IL-6 is heavily influenced by the degree of exercise and hypoxia. ET-1 is an independent predictor of both AMS and its severity. PMID- 26680503 TI - Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome. AB - BACKGROUND AND OBJECTIVES: Obesity hypoventilation syndrome (OHS) is often diagnosed late. The aim of this study was to analyse gender differences at initiation of long-term mechanical ventilation (LTMV) in patients with (OHS), to analyse gender differences in treatment effect and to study how the prescription of LTMV due to OHS has changed over time. METHODS: Data on patients on LTMV due to OHS between 1996 and 2014 were obtained from Swedevox, a nationwide health quality registry of patients on LTMV in Sweden. RESULTS: When starting LTMV, women were generally older (age 64.4 +/- 11.2 vs. 60.1 +/- 12.1 years, p < 0.001), more obese (BMI 43.0 +/- 8.2 vs. 41.5 +/- 7.9 kg/m2, p < 0.001), more hypoxic (PaO2 7.6 +/- 1.5 vs. 7.9 +/- 1.6 kPa, p = 0.001), had more hypercapnia (PaCO2 7.2 +/- 1.3 vs. 6.9 +/- 1.3 kPa, p = 0.001), had higher base excess (6.9 +/- 4.1 vs. 5.8 +/- 4.7 kPa, p < 0.001) and more frequently started LTMV in a non elective situation (43.2% vs. 37.5%, p = 0.026) than men. Improvement of arterial blood gas values or in age-adjusted mortality at one-year follow-up did not differ. During the study period, the age of patients at the initiation of LTMV rose by 3.4 years/decade (P = 0.001) in women and with 1.9 years/decade (P = 0.048) in men but there were no significant changes in BMI (P = 0.425). CONCLUSIONS: Diagnosis of OHS is more delayed in women and as a consequence the disease is more advanced when diagnosed. In spite of this, there is no gender difference in survival rate in patients with OHS treated with LTMV. More and older patients with OHS nowadays gain access to LTMV. PMID- 26680504 TI - Theranostical nanosystem-mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma. AB - Because the primary surgical treatment options for hepatocellular carcinoma (HCC) including hepatic resection and liver transplantation-often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin beta-like protein 1-related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/beta-catenin pathway. The folate-targeted theranostic small interfering RNA (siRNA) nanomedicine Fa-PEG-g-PEI-SPION/psiRNA-TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi-anticancer functions against HCC, intravenous injection of the folate-targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa-PEG-g-PEI-SPION/psiRNA-TBLR1. Moreover, the SPION-encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor-targeted siRNA delivery easily trackable using the clinical MRI technique. CONCLUSION: The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. PMID- 26680505 TI - Proteomic analysis of PSD-93 knockout mice following the induction of ischemic cerebral injury. AB - Postsynaptic density protein-93 (PSD-93) is enriched in the postsynaptic density and is involved in N-methyl-d-aspartate receptor (NMDAR) triggered neurotoxicity through PSD-93/NMDAR/nNOS signaling pathway. In the present study, we found that PSD-93 deficiency reduced infarcted volume and neurological deficits induced by transient middle cerebral artery occlusion (tMCAO) in the mice. To identify novel targets of PSD-93 related neurotoxicity, we applied isobaric tags for relative and absolute quantitative (iTRAQ) labeling and combined this labeling with on line two-dimensional LC/MS/MS technology to elucidate the changes in protein expression in PSD-93 knockout mice following tMCAO. The proteomic data set consisted of 1892 proteins. Compared to control group, differences in expression levels in ischemic group >1.5-fold and <0.66-fold were considered as differential expression. A total of 104 unique proteins with differential abundance levels were identified, among which 17 proteins were selected for further validation. Gene ontology analysis using UniProt database revealed that these differentially expressed proteins are involved in diverse function such as synaptic transmission, neuronal neurotransmitter and ion transport, modification of organelle membrane components. Moreover, network analysis revealed that the interacting proteins were involved in the transport of synaptic vesicles, the integrity of synaptic membranes and the activation of the ionotropic glutamate receptors NMDAR1 and NMDAR2B. Finally, RT-PCR and Western blot analysis showed that SynGAP, syntaxin-1A, protein kinase C beta, and voltage-dependent L-type calcium channels were inhibited by ischemia-reperfusion. Identification of these proteins provides valuable clues to elucidate the mechanisms underlying the actions of PSD-93 in ischemia-reperfusion induced neurotoxicity. PMID- 26680506 TI - Mitochondrial DNA study in domestic chicken. AB - Mitochondrial DNA has the characteristic of quick evolution, matrilineal inheritance, and simple molecular structure, and it serves as the most used marker for molecular study. As an important role of genomics, studying it can help understand the origins, history, and adaptation of domestication. Because of its wide spread popularity, chicken is one of the important domestic animals, which provides humans with a stable source of protein, including both meat and eggs. This article reviews recent studies of chicken mitochondrial DNA. Mitochondrial D-loop and mitochondrial genomics pinpoint the geographic origins of the domestic chicken which was multiple origins; moreover, the mitochondria gene mutation has an association with high-altitude adaptation and the mitochondria-associated diseases' study in poultry is not performed. PMID- 26680507 TI - Right Ventricular Function Is Associated with Left Ventricular Stroke Volume in Patients with Severe Aortic Stenosis and Preserved Ejection Fraction. AB - BACKGROUND: A subset of patients with severe aortic stenosis (AS) have lower stroke volumes and valve gradients despite a normal left ventricular ejection fraction (LVEF), referred to as paradoxical low-flow AS (PLF AS). However, the role of right ventricular (RV) function in patients with severe AS and preserved LVEF is not known. We hypothesized that right ventricular function is associated with left ventricular stroke volume in patients with severe AS and preserved LVEF. METHODS: From an echocardiographic database, we retrospectively identified 102 patients with an indexed aortic valve area <=0.6 cm(2) /m(2) and LVEF >= 50%. We used univariate and multivariate linear regression analysis to assess the association between aortic valve stroke volume index (SVi) and right ventricular systolic function as measured by tricuspid annular plane systolic excursion (TAPSE) and by right ventricular fractional area change (FAC). RESULTS: Our population was 98% male with mean age 77.4 +/- 9.3 years and mean SVi of 36.1 +/- 7.9 mL/m(2) . Forty-four patients (43%) met criteria for PLF AS. TAPSE and FAC were positively associated with SVi in both univariate and multivariate regression analysis after correcting for left ventricular variables (beta coefficient - TAPSE (cm): 4.59 +/- 1.3, P = 0.001; FAC (%): 0.19 +/- 0.08, P = 0.014). Additionally, PLF AS patients had significantly lower mean TAPSE and lower mean FAC when compared dichotomously to normal flow AS patients (P < 0.05). CONCLUSIONS: Right ventricular systolic function assessed by TAPSE and FAC is significantly related to aortic valve flow in patients with severe AS and preserved LVEF. PMID- 26680508 TI - Testing the fecundity advantage hypothesis with Sitobion avenae, Rhopalosiphum padi, and Schizaphis graminum (Hemiptera: Aphididae) feeding on ten wheat accessions. AB - The fecundity advantage hypothesis suggests that females with a large body size produce more offspring than smaller females. We tested this hypothesis by exploring the correlations between life-history traits of three aphid species feeding on ten wheat accessions at three levels of analysis with respect to the host plant: overall, inter-accession, and intra-accession. We found that fecundity was significantly correlated with mean relative growth rate (MRGR), weight gain, and development time, and that the faster aphid develops the greater body and fecundity, depending on aphid species, wheat accession, and analyses level. Larger aphids of all three species produced more offspring overall; this held true for Sitobion avenae and Schizaphis graminum at the inter-accession level, and for S. avenae, Rhopalosiphum padi, and S. graminum for three, five, and eight accessions respectively at the intra-accession level. Only one correlation, between intrinsic rates of natural increase (rm) and MRGR, was significant for all aphid species at all three analysis levels. A more accurate statement of the fecundity advantage hypothesis is that cereal aphids with greater MRGR generally maintain higher rm on wheat. Our results also provide a method for exploring relationships between individual life-history traits and population dynamics for insects on host plants. PMID- 26680509 TI - Comparative mass spectrometric and immunoassay-based proteome analysis in serum of Duchenne muscular dystrophy patients. AB - PURPOSE: Duchenne muscular dystrophy (DMD) is a severe and fatal neuromuscular disease. With the current developments on novel therapeutic strategies for DMD, the need to carefully monitor disease progression or regression upon treatment using molecular markers has become urgent. EXPERIMENTAL DESIGN: 2D LC protein fractionation was performed on patient serum samples, followed by LC-MS/MS-based identifications with label-free quantifications. RESULTS: Protein signatures were compared between patients and healthy (child and adult) controls and between ambulant and nonambulant patients. Various myofibrillar proteins demonstrated differences between DMD patients and controls, likely due to leakiness and breakdown of muscle fibers. Previously reported biomarkers, such as muscle derived titin, myosin, and carbonic anhydrase I (CA1), were verified. MS-based results were compared with ELISA for vitamin D binding protein (GC), fibulin-1 (FBLN1), gelsolin (GSN), and carbonic anhydrase 1 (CA1). CONCLUSIONS AND CLINICAL RELEVANCE: The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis. PMID- 26680510 TI - BaAka women's health and subsistence practices in transitional conservation economies: Variation with age, household size, and food security. AB - OBJECTIVES: Using ethnographic interviews and biological measures, this article investigates changing health and nutrition of a hunter-gatherer population transitioning from a forest-based subsistence system to a horticultural and market-driven lifestyle. METHODS: This study represents biological and dietary recall data for adult female foragers (18+; n = 60) across two villages, Mossapoula (MS) and Yandoumbe (YDBE), in the Dzanga Sangha Protected Areas (APDS), Central African Republic (CAR). Standard anthropometric measurements (height, weight, skinfolds) and hemoglobin values were collected to assess short term nutritional status. RESULTS: BMI was similar across all three age classes in YDBE, but differed amongst women of MS (ANOVA; F = 6.34, df = 30, P = 0.005).Values were lowest among the older women in older age class 3 who also had the greatest number of dependents. Overall SS values were significantly negatively correlated with the number of biological children (r = -0.33, P = 0.01) in both villages. CONCLUSIONS: Here, we identify older BaAka women, caring for their own children and grandchildren, as particularly vulnerable to economic changes and food insecurity. We found older women, especially those in a community with greater restrictions on access to forest resources to have more dependents, reduced market integration, and low BMI relative to younger women in the population. Am. J. Hum. Biol. 28:453-460, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26680511 TI - Assessing health and rehabilitation needs of people with disabilities in Cameroon and India. AB - PURPOSE: To assess the association between disability and serious health problems, and the access and uptake of health and rehabilitation services in Cameroon and India. METHODS: We undertook a population-based case-control study, nested within a survey in Fundong Health District, North West Cameroon (August October 2013) and in Mahbubnagar District, Telangana State, India (February-April 2014). Disability was defined as the presence of self-reported difficulties in functioning or clinical impairments. One control without disability was selected per case, matched by age, gender and cluster. Information was collected using structured questionnaires on: socioeconomic status, health, access to health services and rehabilitation. RESULTS: Cases with disability were significantly more likely to report a serious health problem in the last year compared to controls in both India (OR = 3.2, 95% CI 2.1-4.8) and Cameroon (OR = 1.9, 1.4 2.7). The vast majority of people sought care when seriously ill, and this did not vary between cases and controls. Awareness and use of rehabilitation services was extremely low in both Cameroon and India. CONCLUSIONS: Further focus is needed to improve awareness of rehabilitation services among people with disabilities in India and Cameroon to ensure that their rights are fulfilled and to achieve the goal of Universal Health Coverage. Implications for Rehabilitation People with and without disabilities equally seek health care in India and Cameroon. However, people with disabilities experience more frequent serious health problems than people without. Extremely few people with disabilities were aware of rehabilitation services despite their existence in the study settings. PMID- 26680513 TI - Low quality evidence for effectiveness of fluoridated milk. AB - DATA SOURCES: The Cochrane Oral Health Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, the U.S. National Institutes of Health Trials Register and WHO International Clinical Trials Registry. STUDY SELECTION: Randomised controlled trials with an intervention and follow-up period of at least two years, comparing fluoridated milk with non-fluoridated milk. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias with the Cochrane risk of bias tool. RESULTS: Only one unpublished trial was included. It involved 180 children aged three years at study commencement and was considered to be at high risk of bias. After three years permanent teeth had a caries reduction (mean difference (MD) -0.13, 95% CI -0.24 to -0.02) and primary teeth a caries reduction (MD -1.14, 95% CI -1.86 to -0.42). For primary teeth this is a substantial reduction, equivalent to a prevented fraction of 31%. For permanent teeth,the disease level was very low in the study, resulting in a small absolute effect size. CONCLUSIONS: There is low quality evidence to suggest fluoridated milk may be beneficial to schoolchildren, contributing to a substantial reduction in dental caries in primary teeth. Due to the low quality of the evidence, further research is likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. There was only one relatively small study, which had important methodological limitations on the data for the effectiveness in reducing caries. Furthermore, there was no information about the potential harms of the intervention. Additional RCTs of high quality are needed before we can draw definitive conclusions about the benefits of milk fluoridation. PMID- 26680514 TI - Patients give meaning to changes in health complaints before, during and after the replacement of amalgam restorations. AB - DESIGN: Qualitative, explorative and reflexive thematic analysis. METHODS: Semi structured in-depth interviews were carried out with 12 participants who had all taken part in a previous amalgam removal trial. Follow-up; three months and one, three and five years after amalgam restoration removal and replacement. Interviews were carried out by two researchers at a different location from clinical follow-up. Transcripts were analysed by reading through the written material to establish common themes. NVivo9 software was used to assist further organising themes. Themes were then refined and condensed into the presented findings, which included selected quotes. RESULTS: The authors found the following themes to be important to patients in giving meaning to health complaints before, during and after amalgam removal: Something is not working: betrayed by the body. You are out there on your own. Not being sure of the importance of amalgam removal. The relief experienced after amalgam is removed. To accept, to give up, or to continue the search. CONCLUSIONS: For this group of patients, it was important to remove dental amalgam restorations. However, it remains uncertain of how critical this actually was in relation to their experienced changes in health complaints, as they did not feel that they could credit all positive change to the amalgam removal. For some participants it meant this was no longer a source of worry and for others it helped them move towards accepting their health status. PMID- 26680512 TI - Cancer associated missense mutations in BAP1 catalytic domain induce amyloidogenic aggregation: A new insight in enzymatic inactivation. AB - BRCA1 associated protein 1 (BAP1) is a nuclear deubiquitinase that regulates tumor suppressor activity and widely involves many cellular processes ranging from cell cycle regulation to gluconeogenesis. Impairment of enzymatic activity and nuclear localization induce abnormal cell proliferation. It is considered to be an important driver gene, which undergoes frequent mutations in several cancers. However the role of mutation and oncogenic gain of function of BAP1 are poorly understood. Here, we investigated cellular localization, enzymatic activity and structural changes for four missense mutants of the catalytic domain of BAP1, which are prevalent in different types of cancer. These mutations triggered cytoplasmic/perinuclear accumulation in BAP1 deficient cells, which has been observed in proteins that undergo aggregation in cellular condition. Amyloidogenic activity of mutant BAP1 was revealed from its reactivity towards anti oligomeric antibody in HEK293T cells. We have also noted structural destabilization in the catalytic domain mutants, which eventually produced beta amyloid structure as indicated in atomic force microscopy study. The cancer associated mutants up-regulate heat shock response and activates transcription of genes normally co-repressed by BAP1. Overall, our results unambiguously demonstrate that structural destabilization and subsequent aggregation abrogate its cellular mechanism leading to adverse outcome. PMID- 26680515 TI - Marked variation in malignant transformation rates of oral leukoplakia. AB - DATA SOURCES: Searches were carried out in the Medline, Embase and PubMed databases in July 2014 with a date range, 1960-2013. STUDY SELECTION: Observational cohort studies (either prospective or retrospective) were included. Studies following identical cohorts, case control studies, clinical trials, interventional studies, laboratory studies, experimental studies, studies with no follow-up data, studies of pre-leukoplakia or snuff-induced lesions were excluded. DATA EXTRACTION AND SYNTHESIS: The databases were searched by one reviewer who also screened the studies and evaluated them against the inclusion criteria. Final decision on both inclusion and exclusion of the papers was agreed upon by both authors. RESULTS: A total of 24 studies were included in this review, involving 12,103 patients. Of the 24 studies included 14 were retrospective. Studies were analysed by subgroup, allowing the authors to identify the rate of malignant transformation as 14.9% with a range of 0.13% to 34%. Only 11 studies gave information on the site of malignant transformation; the most common site was the buccal mucosa. For buccal mucosa the malignant transformation was 3.53%, compared to 24.22% for the tongue. Homogenous oral leukoplakia (OL) was most common, however non-homogenous types showed a higher rate of transformation of 13.1%. There was an increased risk of malignant transformation with age. Most studies demonstrated that there is a higher risk of transformation in the female population. CONCLUSIONS: Malignant transformation rate of OL varies from 0.13 to 34% across the 24 studies reviewed here. The authors identified clear risk factors for malignant transformation of oral leukoplakia, including location (tongue), appearance (non-homogenous), increased age and female gender. There was little evidence that surgical intervention had any benefit in reducing the risk of transformation. PMID- 26680516 TI - Nicotine lozenges and behavioural interventions may help smokeless tobacco users to quit. AB - DATA SOURCES: Cochrane Central Register of Controlled trials (CENTRAL); Medline; Embase; PsycINFO. Additional sources were also searched for early versions of the review: Web of Science, Dissertation Abstracts Online, Scopus, Healthstar, ERIC, National Technical Information Service database and Current Contents. STUDY SELECTION: Randomised controlled trials and pseudo-randomised controlled trials allocating smokeless tobacco (ST) users to an intervention or control, or to different interventions. Interventions could be pharmacological (ie nicotine replacement therapy (NRT), bupropion, varenicline) or behavioural, and could be directed at individual ST users or at groups of users. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data about participants, interventions, outcomes and methodological quality. Any discrepancies in extracted data were resolved by consensus. Synthesis followed standard Cochrane methodology. RESULTS: Thirty-four trials were included, 32 from the USA, one from Sweden and one from Sweden and Norway. Sixteen of the trials assessed pharmacological interventions and 19 assessed behavioural interventions (two studies did both). Varenicline increased ST abstinence rates (risk ratio 1.34, 95% confidence interval (CI) 1.08-1.68). Bupropion did not show a benefit of treatment. Neither nicotine patch nor nicotine gum increased abstinence. Nicotine lozenges did increase tobacco abstinence (RR 1.36, 95% CI 1.17-1.59). Behvaioural interventions resulted in a RR of 1.39 (95% CI 1.25-1.55) for those already motivated to quit and 1.37 (95% CI 1.23-1.53) for anyone. CONCLUSIONS: Varenicline, nicotine lozenges and behavioural interventions may help ST users to quit. Confidence in results for nicotine lozenges is limited. Confidence in the size of effect from behavioural interventions is limited because the components of behavioural interventions that contribute to their impact are not clear. PMID- 26680517 TI - DNA-image cytometry has promise for oral cancer detection. AB - DATA SOURCES: The Medline, Embase, PubMed, Elsevier and Web of Science databases and the reference lists of known primary and review papers were scanned for relevant citations. STUDY SELECTION: Prospective and retrospective studies evaluating brush cytology were considered. Only computer-assisted methods that included histologically confirmed disease positive status were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a standardised form. Study quality was assessed by one reviewer using the quality assessment of diagnostic accuracy studies (QUADAS) checklist. Pooled sensitivity and specificity were calculated with 95% CIs (confidence intervals) separately for each study. Likelihood and diagnostic odds ratios were also calculated along with a summary receiver-operating characteristic (SROC) curve analysis. RESULTS: Thirteen studies (eight of OralCDx brush biopsy and five of DNA-image cytometry) reporting on 1981 oral mucosa lesions were included. OralCDx brush biopsy had a pooled sensitivity of 86% (95% CI; 81-90) and pooled specificity of 81% (95% CI; 78-85). The pooled sensitivity and specificity of DNA-image cytometry were 89% (95% CI; 83-94) and 99% (95% CI; 97-100). Diagnostic odds ratio estimates for OralCDx brush biopsy and DNA-image cytometry were 20.36 (95% CI; 2.72-152.67) and 446.08 (95% CI; 73.36-2712.43), respectively. Study size was found to be closely related to heterogeneity among studies and analysis suggested publication bias in relation to OralCDx brush biopsy. CONCLUSIONS: The results of this meta-analysis suggest that DNA-image cytometry has a highly significant potential over OralCDx brush biopsy as an accurate and simple diagnostic tool for clinically suspected oral precancer and oral cancer. PMID- 26680518 TI - Fluoride gel effective at reducing caries in children. AB - Data SOURCES: Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline , Embase, CINAHL, LILACS, ProQuest Dissertations and Theses, the Web of Science Conference Proceedings, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. STUDY SELECTION: Randomised or quasi-randomised controlled trials comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years were considered. Studies had to be at least one year in duration with a frequency of application of at least once a year with blind outcome assessment. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). DATA EXTRACTION AND SYNTHESIS: At least two reviewers extracted data and assessed risk of bias. The primary measure of effect was the prevented fraction (PF). Where data could be pooled random-effects meta-analyses were conducted. Potential sources of heterogeneity were examined in random-effects meta-regression analyses. RESULTS: Twenty-eight trials involving 9140 children and adolescents were included. Most of the studies (20) were at high risk of bias, with eight at unclear risk of bias. Twenty-five trials (8479 participants) provided data for meta-analysis on permanent teeth, with a D(M)FS pooled prevented fraction (PF) estimate of 28% (95% CI; 19-36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the ten trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials.A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.For primary teeth the d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) = 20% (95%CI; 1% - 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. CONCLUSIONS: The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects. PMID- 26680519 TI - Short-term improvement in oral self-care of adolescents with social-cognitive theory-guided intervention. AB - DESIGN: Cluster randomised controlled trial. INTERVENTION: Clusters of adolescents (classrooms of 15- to 16-year-olds) in each school were allocated either into a control group or into an intervention group. The interventions consisted of peer cooperation (peer support) and peer interactive learning (observational learning) facilitated through feedback from a dentist (professional support). Three intervention sessions with preselected pairs of adolescents were delivered in the first three weeks. Gender, family socio economic status (baseline) and different social-cognitive domain variables (baseline, six, and 12 months) were assessed using a questionnaire. OUTCOME MEASURE: Dental plaque levels were the primary outcome measure and they were measured at baseline, after the intervention measured only in the social cognitive theory-guided group, at six and 12 months. RESULTS: At the six-month follow-up there was a statistically significant difference in means +/- SD between the social-cognitive intervention group (27.4 +/- 19.4) and the control group (35.1 +/- 20.0). At the 12-month follow-up, there was no statistically significant difference in means +/- SD between the social-cognitive intervention group (27.4 +/- 18.5) and the control group (31.9 +/- 17.8). Variations in dental plaque levels at different time periods were explained by the following predictors: family's socio-economic status, social-cognitive domain variables, group affiliation and baseline plaque levels. CONCLUSIONS: Social-cognitive theory-guided interventions improved oral self-care of adolescents in the short term. This improvement lasted only for five months after the intervention was discontinued. PMID- 26680520 TI - Clear aligners for orthodontic treatment? AB - DATA SOURCES: PubMed/Medline, Embase, Cochrane Central Register of Controlled Clinical trials (CENTRAL), Web of Knowledge, SCOPUS, Google Scholar and LILACS databases. STUDY SELECTION: Clinical prospective and retrospective studies of orthodontic treatment with clear aligners on patients over the age of 15 that included clear descriptions of the materials and applied technique were included. Selection was undertaken independently by two reviewers. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data independently with study quality being assessed using the grading system described by the Swedish Council on Technology Assessment in Health Care (SBU). A narrative summary of the findings was presented. RESULTS: Eleven studies involving a total of 480 patients were included consisting of two randomised controlled trials, five prospective studies and four retrospective studies. Six studies were considered to be of moderate quality, the remainder of limited quality. CONCLUSIONS: Most of the studies presented with methodological problems: small sample size, bias and confounding variables, lack of method error analysis, blinding in measurements, and deficient or missing statistical methods. The quality level of the studies was not sufficient to draw any evidence-based conclusions. PMID- 26680521 TI - Review finds failure rates lower for delayed loaded submerged dental implants. AB - DATA SOURCES: PubMed, Web of Science, Cochrane Oral Health Group Trials Register, ClinicalTrials.gov, CenterWatch.com, ClinicalConnection.com. STUDY SELECTION: Randomised and non-randomised studies were included comparing implant failure rates in any group of patients receiving submerged versus immediately loaded non submerged dental implants. Selection was conducted independently by three reviewers. DATA EXTRACTION AND synthesis: Titles and abstracts of all reports identified through the electronic searches were read independently by the three authors. Studies were selected based on inclusion and exclusion criteria, with disagreements resolved through discussion. Study quality was assessed using the Cochrane risk of bias tool. Implant failure and post-operative infection were the dichotomous outcome measures evaluated. Weighted mean differences (WMD) were calculated and meta-analysis conducted. RESULTS: Twenty eight studies, consisting of six randomized clinical trials, 14 controlled clinical trials and eight retrospective analyses were included. 23 studies were considered to be at high risk of bias, one at moderate risk and four at low risk of bias. The relative risk (RR) of failure was higher in immediately loaded implants RR = 1.78 (95% CI; 1.12- 2.83). The number needed to treat (NNT) to prevent one patient having an implant failure is 50 (95% CI; 25-100). Analysis suggests the possibility of publication bias. CONCLUSIONS: The difference between immediately loading and delayed loading of an implant statistically affected the implant failure rate. No statistically significant effects on the occurrence of post-operative infection were observed between the two techniques. Results should be interpreted with caution due to lack of control of confounding factors, the retrospective design of some studies included and the small cohort sizes within the studies. PMID- 26680522 TI - Good short-term survival rates for posterior resin composite restorations. AB - DATA SOURCES: PubMed, the Cochrane Library and the databases of the Centre for Reviews and Dissemination were searched. STUDY SELECTION: Prospective randomised controlled trials (RCTs), clinical controlled trials (CCTs) and observational studies of Class I and/or Class II resin composite restorations with a sample size of more than 40 individuals or teeth and longer than four years follow-up were considered. RESULTS: Eight studies involving a total of 910 restorations in 420 patients were included. Seven of the eight studies were completed by the same research group with follow-up times ranging from four to 12 years. There were 80 failures of restorations in total, ranging from two to 17 per study. A majority of the fractures of the restoration or the tooth and endodontic complications occurred during the first three years of follow-up. Caries occurred later, more than 75% after three years in service. The overall incidence rate for all causes of failure was 1.55 lost restorations per 100 restoration years. Survival rate at four years = 0.93 (95% CI; 0.91- 0.95). One study (74 teeth) provided data at 12 years with a survival rate = 0.86 (95% CI; 0.82;0.89). The most common biological reason for failure (a total of 31 restorations) was secondary caries, with or without fracture of the restoration. The overall quality of the evidence was low. CONCLUSIONS: The overall survival proportion of posterior resin composite restorations is high. The major reasons for failure are secondary caries and restoration fracture, which supports the importance of adequate follow-up time as secondary caries often occurred after three years or later. PMID- 26680523 TI - Hygiene-therapists could be used to screen for dental caries and periodontal disease. AB - METHODOLOGY: A purposive sample of large NHS dental practices with a minimum of three surgeries employing at least one hygiene-therapist (HT) was taken. Asymptomatic patients attending for routine checkups who consented to the study underwent a screen by H-T for dental caries and periodontal disease (index test) followed by a screen by a general dental practitioner (reference test). Patients were recruited consecutively. H-Ts and dentists attended a compulsory training day, which covered recruitment, consenting, screening process, calibration using stock photographs and patient record form completion. Diagnostic threshold for caries was any tooth in the patient's mouth that showed evidence of frank cavitation or shadowing and opacity that would indicate dental caries into the dentine. The diagnostic threshold for periodontal disease was any pocket in the patient's mouth where the black-band of a basic periodontal examination (BPE) probe (3.5 to 5.5 mm) partially or totally disappeared (ie BPE code 3). The index test was compared with the reference test to determine true-positive, false positive, false-negative and true-negative values. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic odds ratios are shown in Table 1. RESULTS: Eighteen hundred and ninety-nine patients consented to dental screening with 996 patients being randomly allocated to see the dentist first and 903 H-T first. The time interval between the index and reference test never exceeded 21 minutes. With the exception of two practices failing to collect data on smoking and dentures there were no missing results regarding the outcome of a positive or negative screening decision. No adverse events were reported. Mean screening time was five min 25 s for H-Ts and four min 26 s for dentists. Dentists identified 668 patients with caries (Prevalence of 0.35) while H-Ts classified 548 positive and correctly identified 1,047 of the 1,231 patients with no caries. Dentists identified 1074 patients with at least one pocket exceeding 3.5 mm in depth. Of these 935 were correctly identified by the H-Ts. For the 825 screened as negative by the dentist H-Ts correctly identified 621. CONCLUSIONS: The results suggest that hygiene-therapists could be used to screen for dental caries and periodontal disease. This has important ramifications for service design in public-funded health systems. PMID- 26680524 TI - No evidence for stopping long-term aspirin therapy before tooth extraction. AB - DATA SOURCES: PubMed, ScienceDirect and EBSCOhost databases. STUDY SELECTION: Prospective randomised controlled trials (RCTs) or controlled trials. DATA EXTRACTION AND SYNTHESIS: Two independent investigators extracted data. The primary measured outcomes were rates of haemorrhage and bleeding time. Disagreements were clarified with a third investigator. Relevant authors were contacted if any relevant data was missing. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of evidence. The authors used standardised mean difference or relative risk to evaluate each outcome. RESULTS: Ten studies were included, three randomised controlled trials and seven controlled trials. A total of 1752 patients were enrolled in the meta-analysis; the study group comprised 529 patients on long-term aspirin therapy, and the control group comprised 1223 patients. The risk of post-operative haemorrhage was significantly higher in patients on aspirin therapy (relative risk=2.46; 95% confidence interval: 1.45 4.81) but bleeding time was not significantly different between the two groups (standardised mean difference=0.63; 95% CI: - 0.04 to 1.31). CONCLUSIONS: Increased rates of haemorrhage are observed in patients on long-term aspirin therapy. The authors recommend not stopping long-term aspirin prior to dental extraction, and local measures for haemostasis should be enhanced when required. PMID- 26680525 TI - Socioeconomic indicators and traumatic dental injury. AB - DATA SOURCES: PubMed, ISI, LILACS, Cochrane Library and Embase databases were searched. STUDY SELECTION: Epidemiological studies (cross-sectional, case control, cohort clinical trials) addressing possible associations between socioeconomic indicators (eg mother's schooling, household income, number of children, type of school) and traumatic dental injury in the primary dentition were considered. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies. with study quality being assessed using the Newcastle-Ottawa Scale (NOS). Data were extracted for categorical variables considered risk factors for TDI and recorded based on the distribution and frequency of TDI among children exposed to risk factors vs the frequency among children not exposed to risk factors. Meta-analysis was undertaken. RESULTS: Sixteen studies (15 cross sectional studies and one cohort study) were included. A wide range of socioeconomic indicators were investigated including; parents' schooling, parents' employment status, home ownership, having changed address in the previous year, income, family structure, number of residents in the home, number of children in the family, type of school and socioeconomic status. Children from families with household income less than two times average salary (US$ 592) (OR: 0.77; 95% CI: 0.66-0.90) or more than three times the average salary (US$ 888) (OR: 0.76; 95% CI: 0.65-0.89) had a significantly lower chance of having TDI in the primary dentition. TDI was not associated with socioeconomic status (high vs low - OR: 0.77; 95% CI: 0.43-1.36; high vs medium - OR: 1.03; 95% CI: 0.72-1.48; medium vs low - OR: 0.70; 95% CI: 0.42-1.19), house ownership (owned vs rented - OR: 1.28; 95% CI: 0.98-1.66), mother's schooling (OR: 0.89; 95% CI: 0.74-1.08), or father's schooling (OR: 1.01; 95% CI: 0.62-2.74). CONCLUSIONS: The scientific evidence demonstrates that socioeconomic indicators are not associated with TDI in the primary dentition. The evidence of an association between a low income and TDI is weak. In general, studies had low risk of bias. Further prospective cohort studies are needed to confirm this association. PMID- 26680526 TI - Unclear results for the use of botulinum toxin therapy for TMD pain. AB - DATA SOURCES: A comprehensive search was carried out on major databases such as PubMed, EMBASE and Cochrane CENTRAL. Reference lists of the included studies were explored along with journals likely to contain studies relevant to the topic. The search was restricted to the English language. STUDY SELECTION: The inclusion criteria included randomised and quasi-randomised controlled trials including parallel or cross-over studies comparing botulinum toxin therapy (BTX) versus any alternative intervention or placebo. DATA EXTRACTION AND SYNTHESIS: Quality assessment and data extraction were done following the Cochrane risk of bias tool and recommendations. All of the steps in the review, including the search and selection process, were done independently by two reviewers. Disagreements were discussed with one another until consensus was reached. RESULTS: Five relevant studies were included in the review, which consisted of 117 participants. Two trials revealed a significant inter-group difference in myofascial pain reduction. Another trial that compared BTX with fascial manipulation showed no significant difference in pain relief for temporomandibular disorders (TMDs), while the remaining two trials showed no significant difference between the BTX and placebo groups. Meta-analysis was not performed due to the considerable variation in study methods and evaluation of the results. All five studies were targeted primarily on the masseter and temporalis muscles and most of them administered injections at bilateral muscle sites. The methods used to find the muscles to target were all based on physical examination, with three studies using electromyography (EMG) as guidance. The dose of BTX ranged from 70U to 300U, the majority used being 100-150U. All studies gave a single session of BTX and re-evaluated participants at least one month following the injection. CONCLUSIONS: No consensus could be reached on the therapeutic benefit of BTX on TMDs. PMID- 26680530 TI - Oxidative stress, neurotoxicity, and metallothionein (MT) gene expression in juvenile rock fish Sebastes schlegelii under the different levels of dietary chromium (Cr(6+)) exposure. AB - Juvenile Sebastes schlegelii were exposed for 4 weeks with the different levels of dietary chromium (Cr(6+)) concentration (0, 30, 60, 120 and 200mg/kg). The superoxide dismutase (SOD) activity, glutathione S-transferase (GST) activity, and glutathione (GSH) level of liver and gill were evaluated after 4 weeks exposure. The SOD and GST activity of liver and gill was significantly increased in the concentration of 240mg/kg after 2 weeks and over 120mg/kg after 4 weeks, whereas a considerable decrease in the concentration of 240mg/kg after 2 weeks and over 120mg/kg after 4 weeks was observed in the GSH levels of liver and gill. In neurotoxicity, AChE activity was significatly inhibited in brain in the concentration of 240mg/kg after 2 weeks and over 60mg/kg after 4 weeks and muscle in the concentration of 240mg/kg after 2 weeks and over 120mg/kg after 4 weeks. Metallothionein (MT) gene in liver was considerably increased over 120mg/kg after 2 weeks and at 30, 120, and 240mg/kg after 4 weeks by dietary chromium exposure. The results indicate that dietary Cr exposure over 120mg/kg can induce substantial alterations in antioxidant responses, AChE activity and MT gene expression. PMID- 26680531 TI - COR a 14-specific IgE predicts symptomatic hazelnut allergy in children. PMID- 26680533 TI - Prevalence of Risk Factors for Coronary Artery Disease in Pennsylvania (USA) Firefighters. AB - INTRODUCTION: Firefighting is a physically demanding profession. Heart disease remains the number one killer of firefighters. Many firefighters have multiple risk factors, putting them at risk for sudden cardiac events. The purpose of this study was to describe the prevalence of risk factors for heart disease in a convenience sample of Pennsylvania (USA) firefighters. METHODS: A convenience sample of 160 firefighters in western Pennsylvania had height, weight, waist circumference, blood pressure, and body mass index (BMI) assessed, and then were surveyed to measure their knowledge of cardiovascular risk factors. Data analysis included subgroup comparisons of age, BMI, waist circumference, and exercise for their impact on health risks in the study cohort. In particular, the researchers were interested in understanding whether the knowledge of risk was associated with lower measures of risk. RESULTS: Eighteen firefighters (4%) reported a history of coronary artery disease (including stents/interventions). In this group, 69% to 82% correctly identified age, hypertension (HTN), high cholesterol, smoking, obesity, sedentary lifestyle, and family history as risk factors for coronary artery disease. Fourteen percent were smokers, 41% had HTN, 38% had pre HTN with only 12% receiving treatment, and 13.5% were treated for high cholesterol. Fifty-eight percent exercised regularly. CONCLUSIONS: While a majority of firefighters were able to identify risk factors for coronary artery disease, many could not. Eighteen (4%) had a history of coronary artery disease, including interventions. Many had several of the risk factors indicated, which highlights the need for an organized national approach to address the medical screening/evaluation, nutrition, and exercise components of firefighter fitness. PMID- 26680532 TI - Structure-function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family. AB - Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6 oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-a-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications. PMID- 26680534 TI - Beyond 'working with men and boys': (re)defining, challenging and transforming masculinities in sexuality and health programmes and policy. PMID- 26680535 TI - Hegemonic masculinity: combining theory and practice in gender interventions. AB - The concept of hegemonic masculinity has been used in gender studies since the early-1980s to explain men's power over women. Stressing the legitimating power of consent (rather than crude physical or political power to ensure submission), it has been used to explain men's health behaviours and the use of violence. Gender activists and others seeking to change men's relations with women have mobilised the concept of hegemonic masculinity in interventions, but the links between gender theory and activism have often not been explored. The translation of 'hegemonic masculinity' into interventions is little examined. We show how, in South Africa and Sweden, the concept has been used to inform theoretically-based gender interventions and to ensure that men are brought into broader social efforts to build gender equity. We discuss the practical translational challenges of using gender theory broadly, and hegemonic masculinity in particular, in a Swedish case study, of the intervention Machofabriken [The Macho Factory], and illustrate how the concept is brought to life in this activist work with men. The concept has considerable practical application in developing a sustainable praxis of theoretically grounded interventions that are more likely to have enduring effect, but evaluating broader societal change in hegemonic masculinity remains an enduring challenge. PMID- 26680536 TI - Masculinity, sexuality and vulnerability in 'working' with young men in South African contexts: 'you feel like a fool and an idiot ... a loser'. AB - South Africa has seen a rapid increase in scholarship and programmatic interventions focusing on gender and sexuality, and more recently on boys, men and masculinities. In this paper, we argue that a deterministic discourse on men's sexuality and masculinity in general is inherent in many current understandings of adolescent male sexuality, which tend to assume that young women are vulnerable and powerless and young men are sexually powerful and inevitably also the perpetrators of sexual violence. Framed within a feminist, social constructionist the oretical perspective, the current research looked at how the masculinity and sexuality of South African young men is constructed, challenged or maintained. Focus groups were conducted with young men between the ages of 15 and 20 years from five different schools in two regions of South Africa, the Western and Eastern Cape. Data were analysed using Gilligan's listening guide method. Findings suggest that participants in this study have internalised the notion of themselves as dangerous, but were also exploring other possible ways of being male and being sexual, demonstrating more complex experiences of manhood. We argue for the importance of documenting and highlighting the precariousness, vulnerability and uncertainty of young men in scholarly and programmatic work on masculinities. PMID- 26680537 TI - Changing what it means to 'become a man': participants' reflections on a school based programme to redefine masculinity in the Balkans. AB - Calls to engage men and boys in efforts to promote health, prevent violence and advance gender equality have grown in recent years. However, there remains little evidence or reflection on how most effectively to change harmful norms related to masculinity. The study addresses this gap by exploring the perspectives of participants in the Young Men Initiative (YMI), an innovative programme that aimed to promote healthier masculinities among boys attending vocational high schools in several Balkan countries through educational workshops, residential retreats and a social marketing campaign. Qualitative data were collected through 37 in-depth interviews and 11 focus-group discussions with boys, youth facilitators and teachers. Findings from four schools (in Belgrade, Sarajevo, Prishtina and Zagreb) suggest that several elements of the programme resonated strongly with participants and supported their meaningful engagement in project activities. Five themes emerged as most salient in identifying how and why specific aspects of YMI positively influenced participants: personal reflection, experience-based learning, connections with youth facilitators, new peer groups and aspirational messaging. Building on these insights, the study highlights potentially useful strategies for other programmes seeking to reach boys and transform their understanding of masculinity. PMID- 26680538 TI - Noncoding and coding transcriptome responses of a marine diatom to phosphate fluctuations. AB - Phosphorus (P) is an essential element to all living cells, yet fluctuations in P concentrations are recurrent in the marine environment. Diatoms are amongst the most successful phytoplankton groups, adapting to and surviving periods of suboptimal conditions and resuming growth as soon as nutrient concentrations permit. A knowledge of the molecular underpinnings of diatom ecological success is, however, still very incomplete. By strand-specific RNA sequencing, we analyzed the global transcriptome changes of the diatom Phaeodactylum tricornutum in response to P fluctuations over a course of 8 d, defining five distinct physiological states. This study reports previously unidentified genes highly responsive to P stress in P. tricornutum. Our data also uncover the complexity of the P. tricornutum P-responsive sensory and signaling system that combines bacterial two-component systems with more complex pathways reminiscent of metazoans. Finally, we identify a multitude of novel long intergenic nonprotein coding RNAs (lincRNAs) specifically responsive to P depletion, suggesting putative regulatory roles in the regulation of P homeostasis. Our work provides additional molecular insights into the resilience of diatoms and their ecological success, and opens up novel routes to address and explore the function and regulatory roles of P. tricornutum lincRNAs in the context of nutrient stress. PMID- 26680539 TI - A two-layered machine learning method to identify protein O-GlcNAcylation sites with O-GlcNAc transferase substrate motifs. AB - Protein O-GlcNAcylation, involving the beta-attachment of single N acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues, is an O-linked glycosylation catalyzed by O-GlcNAc transferase (OGT). Molecular level investigation of the basis for OGT's substrate specificity should aid understanding how O-GlcNAc contributes to diverse cellular processes. Due to an increasing number of O-GlcNAcylated peptides with site-specific information identified by mass spectrometry (MS)-based proteomics, we were motivated to characterize substrate site motifs of O-GlcNAc transferases. In this investigation, a non-redundant dataset of 410 experimentally verified O GlcNAcylation sites were manually extracted from dbOGAP, OGlycBase and UniProtKB. After detection of conserved motifs by using maximal dependence decomposition, profile hidden Markov model (profile HMM) was adopted to learn a first-layered model for each identified OGT substrate motif. Support Vector Machine (SVM) was then used to generate a second-layered model learned from the output values of profile HMMs in first layer. The two-layered predictive model was evaluated using a five-fold cross validation which yielded a sensitivity of 85.4%, a specificity of 84.1%, and an accuracy of 84.7%. Additionally, an independent testing set from PhosphoSitePlus, which was really non-homologous to the training data of predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (84.05%) and outperform other O-GlcNAcylation site prediction tools. A case study indicated that the proposed method could be a feasible means of conducting preliminary analyses of protein O-GlcNAcylation and has been implemented as a web-based system, OGTSite, which is now freely available at http://csb.cse.yzu.edu.tw/OGTSite/. PMID- 26680541 TI - Congratulations! The 2015 Placenta prizes. PMID- 26680542 TI - Gas-Phase Generation and Decomposition of a Sulfinylnitrene into the Iminyl Radical OSN. AB - The dipolar oxathiazyne-like sulfinylnitrene RS(O)N, a highly reactive alpha-oxo nitrene, has been rarely investigated. Upon flash vacuum pyrolysis of sulfinyl azide CF3S(O)N3 at 350 degrees C, an elusive sulfinylnitrene CF3S(O)N was generated in the gas phase in its singlet ground state and was characterized by matrix-isolation IR spectroscopy. Further fragmentation of CF3S(O)N at 600 degrees C produced CF3 and a novel iminyl radical OSN, an SO2 analogue, which were unambiguously identified by IR spectroscopy. Consistent with the experimental observations, DFT calculations clearly support a stepwise decomposition mechanism of CF3S(O)N3. PMID- 26680540 TI - Integrative Omics Analysis Reveals Post-Transcriptionally Enhanced Protective Host Response in Colorectal Cancers with Microsatellite Instability. AB - Microsatellite instability (MSI) is a frequent and clinically relevant molecular phenotype in colorectal cancer. MSI cancers have favorable survival compared with microsatellite stable cancers (MSS), possibly due to the pronounced tumor infiltrating lymphocytes observed in MSI cancers. Consistent with the strong immune response that MSI cancers trigger in the host, previous transcriptome expression studies have identified mRNA signatures characteristic of immune response in MSI cancers. However, proteomics features of MSI cancers and the extent to which the mRNA signatures are reflected at the protein level remain largely unknown. Here, we performed a comprehensive comparison of global proteomics profiles between MSI and MSS colorectal cancers in The Cancer Genome Atlas (TCGA) cohort. We found that protein signatures of MSI are also associated with increased immunogenicity. To reliably quantify post-transcription regulation in MSI cancers, we developed a resampling-based regression method by integrative modeling of transcriptomics and proteomics data sets. Compared with the popular simple method, which detects post-transcriptional regulation by either identifying genes differentially expressed at the mRNA level but not at the protein level or vice versa, our method provided a quantitative, more sensitive, and accurate way to identify genes subject to differential post-transcriptional regulation. With this method, we demonstrated that post-transcriptional regulation, coordinating protein expression with key players, initiates de novo and enhances protective host response in MSI cancers. PMID- 26680543 TI - Effects of Nigella sativa L. seed oil on intima-media thickness and Bax and Caspase 3 expression in diabetic rat aorta. AB - OBJECTIVE: Hyperglycaemia is an important risk factor for the development and progression of the macrovascular and microvascular complications that occur in diabetes. The expression of apoptotic markers in the aortic medial layer of diabetic rats and the effects of N. sativa L. seed oil on the expression of these markers were investigated in this study. METHODS: Four-month-old adult female Wistar rats (n=21) were divided into 3 groups: Group 1, control; Group 2, diabetes and Group 3, diabetes+N. sativa L. seed oil. Group 3 received 0.2 mg/kg/day N. sativa L. seed (black cumin) oil intraperitoneally 6 days per week for 30 days. At the end of the experiment, abdominal and thoracic aortas of all animals were collected and fixed in 10% formalin solution. Then, 5-MUm-thick sections were stained with Verhoeff-Van Gieson stain to evaluate Bax and Caspase 3 expression. Tunica intima-media thickness was measured using the stained sections. RESULTS: There were no significant differences in abdominal or thoracic aortic intima-media thickness among the 3 groups. However, there were significant differences in Bax and Caspase 3 expression in the tunica media of the thoracic and abdominal aortas between Group 1 and Group 2 (p<0.05) and between Group 2 and Group 3 (p<0.05) evaluated with the Kruskal-Wallis and Mann-Whitney U tests. CONCLUSION: It is understood that N. sativa L. seed oil is effective against diabetes. N. sativa L. seed oil is a plant material and has value for further investigation to develop diabetes treatment strategies for preventing apoptosis in vascular structures. PMID- 26680544 TI - Comparison of health-related quality of life among patients using novel oral anticoagulants or warfarin for non-valvular atrial fibrillation. AB - OBJECTIVE: The aim of this study was to compare health-related quality of life (HRQoL) measures between novel oral anticoagulants (NOACs) and warfarin-treated Turkish patients who had been started on oral anticoagulants (OACs) due to non valvular atrial fibrillation (AF) and to determine the effects of OACs on patient's emotional status, anxiety and depression. METHODS: A total of 182 patients older than 18 years with non-valvular AF and being treated with OACs for at least 6 months according to current AF guidelines who were admitted to outpatient clinics between July 2014 and January 2015 were included in this cross sectional study. The exclusion criteria were receiving OACs for conditions other than non-valvular AF and being unable to answer the questionnaire. A questionnaire was administered to all participants to evaluate HRQoL, depression and anxiety. The mean differences between the groups were compared using Student's t-test; the Mann-Whitney U test was applied for comparisons of the medians. RESULTS: The annual number of hospital admissions was significantly higher in the warfarin group (p<0.001), and all HRQoL scores were significantly lower and Hospital Anxiety and Depression Scale (HADS) score was higher in the warfarin group (p<0.001). History of any type of bleeding was significantly higher in the warfarin group (p<0.001). However, none of the patients had major bleeding. Among patients who experienced bleeding, all HRQoL scores were significantly lower and HADS score was significantly higher (p<0.001 and p=0.002, respectively). CONCLUSION: Warfarin-treated patients had higher levels of self reported symptoms of depression and anxiety and compromised HRQoL when compared with NOAC-treated patients. The results may be explained by higher rates of bleeding episodes and higher number of hospital admissions, which may cause restrictions in life while on warfarin treatment. PMID- 26680545 TI - Prediction of recurrence after cryoballoon ablation therapy in patients with paroxysmal atrial fibrillation. AB - OBJECTIVE: The purpose of this study was to investigate the factors predicting the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation (PAF) who underwent cryoablation of the pulmonary veins (PVs). METHODS: Fifty-one patients (54.6+/-10.4 years) with paroxysmal AF who underwent the cryoablation of the PVs were to the prospective trial. The clinical risk factors and echocardiographic parameters [left atrial (LA) diameter, left ventricular ejection fraction and dimensions, left atrial spontaneous echo contrast (LASEC), mitral annulus calcification (MAC), left atrial appendage emptying peak flow velocity (LAAV), and PV flow] were assessed before the cryoablation procedure. Patients with PAF who refused to use any medication because of intolerance or presentation of resistant symptoms, despite the use of at least one antiarrhythmic drug were enrolled to the study, patients with LA/LAA thrombus on echocardiographic examination, severe valvular disease, pericardial fluid, and abnormal thyroid function tests as well as systemic disease were excluded from the study. All parameters were tested for their ability to predict the recurrence of AF during a 1-year follow-up period. RESULTS: During the period of follow-up, AF recurred in 16 of 51 patients (31.3%/year). All significant parameters associated with the recurrence of AF were evaluated in multivariate logistic regression analysis. The presence of MAC (p<0.001) as well as LA diameter (p<0.0001), LAAV of <30 cm/s (p<0.0001), PV flow systolic wave velocity (p<0.0001), and LASEC (p<0.0001) were detected as independent predictors of recurrence. In the receiver operating characteristic analysis, LAAV of >30 cm/s had a sensitivity of 85% and a specificity of 95% for predicting success after ablation (AUC=0.813; 95% CI: 0.76-0.92; p<0.0001). CONCLUSION: The presence of MAC, increased LA diameter, the existence of LASEC, low LAAV, and low peak PV systolic wave velocity are parameters that can predict the recurrence of AF after cryoablation. PMID- 26680547 TI - Assessment of the left ventricular systolic function in cardiac syndrome X using speckle tracking echocardiography. AB - OBJECTIVE: The aim of this study was to evaluate left ventricular (LV) systolic strain by speckle tracking echocardiography (STE) and real-time three-dimensional echocardiography (3-DE) for the early detection of myocardial dysfunction in patients with cardiac syndrome X (CSX). METHODS: We compared 34 patients with CSX (18 females, mean age 47.9+/-10.0 years) with 41 healthy persons as a control group (23 females, mean age 50.6+/-9.9 years). Inclusion criteria for CSX were typical angina, a positive exercise ECG stress test, and angiographically documented normal coronary arteries. Exclusion criteria for both groups were hypertension, valvular heart disease, cardiomyopathies, inflammatory diseases, myocarditis, vasculitis, arthropathies, Tietze's syndrome, gastrointestinal diseases, aortic diseases, hormone replacement therapy, arrhythmias, liver diseases, and alcohol use. All subjects underwent two-dimensional STE and 3-DE to assess resting LV function. STE measures were taken from the basal septum, mid septum, apical septum, apex, apicolateral, mid-lateral, basal lateral, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal walls. Student's t-test, Mann-Whitney U test, and chi-square test were used to statistically analyze data. RESULTS: LV echo ejection fraction (EF) and systolic wave peak velocity were similar for both groups. Regional mean longitudinal strain (-17.7+/-2.5% vs. -19.8+/-1.8%; p<0.0001) was significantly lower in patients with CSX than in healthy control patients. However, regional mean circumferential strain values (-22.0+/-1.6% vs. -22.2+/-2.3%; p=0.78) did not differ significantly between the two groups. CONCLUSION: Significant impairment of LV longitudinal myocardial systolic function was detected with STE in patients with CSX, although normal 3-D EF and tissue Doppler imaging systolic parameters were observed. Arteriosclerosis of small coronary arteries and microvascular dysfunction may affect myocardial longitudinal strain. PMID- 26680546 TI - Comparison of the Framingham risk and SCORE models in predicting the presence and severity of coronary artery disease considering SYNTAX score. AB - OBJECTIVE: Although various risk stratification models are available and currently being used, the performance of these models in different populations is still controversial. We aimed to investigate the relation between the Framingham and SCORE models and the presence and severity of coronary artery disease, which is detected using the SYNTAX score. METHODS: The observational cross-sectional study population consisted of 227 patients with a mean age of 63.3+/-9.2 years. The patients were classified into low- and high-risk groups in the Framingham and SCORE models separately. Following coronary angiography, the patients were classified into SYNTAX=0 (SYNTAX score 0), low SYNTAX (SYNTAX score 1-22), and high SYNTAX (SYNTAX score>22) groups. The relation between the risk models and SYNTAX score was evaluated by student t test, Mann-Whitney U test or Kruskal Wallis test and Receiver operating characteristic analysis were used to detect the discrimination ability in the prediction of SYNTAX score>0 and a high SYNTAX score. RESULTS: Both the Framingham and SCORE models were found to be effective in predicting the presence of coronary artery disease, and neither of the two models had superiority over each other [AUC=0.819 (0.767, 0.871) vs. 0.811 (0.757, 0.861), p=0.881]. Furthermore, both models were also effective in predicting the extent and severity of coronary artery disease [AUC=0.724 (0.656, 0.798) vs. 0.730 (0.662, 0.802), p=0.224]. When the subgroups were analyzed, the SCORE model was found to be better in predicting coronary artery disease extent and severity in subgroups of men and diabetics {[AUC=0.737 (0.668, 0.844) vs. 0.665 (0.560, 0.790), p=0.019], [AUC=0.733 (0.684, 0.798) vs. 0.680 (0.654, 0.750) p=0.029], respectively). CONCLUSION: In addition to their role in predicting cardiovascular events, the use of the Framingham and SCORE models may also have utility in predicting the extent and severity of coronary artery disease. The SCORE risk model has a slightly better performance than the Framingham risk model. PMID- 26680548 TI - Investigation of X-ray permeability of surgical gloves coated with different contrast agents. AB - OBJECTIVE: We aimed to investigate the effectiveness and radiation protection capability of latex gloves coated with various contrast agents as an alternative to lead gloves. METHODS: The following six groups were created to evaluate the permeability of X-ray in this experimental study: lead gloves, two different non ionic contrast media (iopromide 370/100 mg I/mL and iomeprol 400/100 mg I/mL), 10% povidone-iodine (PV-I), 240/240 g/mL barium sulphate and a mixture of equal amounts of all contrast agents. A radiation dose detector was placed in coated latex gloves for each one. The absorption values of radiation from latex gloves coated with various contrast agents were measured and compared with the absorption of radiation from lead gloves. This study was designed as an 'experimental study'. RESULTS: The mean absorption value of X-ray from lead gloves was 3.0+/-0.08 uG/s. The mean absorption values of X-ray from latex gloves coated with various contrast agents were 3.7+/-0.09 uG/s (iopromide 370/100 mg I/mL), 3.6+/-0.09 uG/s (iomeprol 400/100 mg I/mL), 3.7+/-0.04 uG/s (PV-I), 3.1+/ 0.07 uG/s (barium sulphate) and 3.8+/-0.05 uG/s (mixture of all contrast agents). Latex gloves coated with barium sulphate provided the best radiation absorption compared with latex gloves coated with other radiodense contrast agents. CONCLUSION: Latex gloves coated with barium sulphate may provide protection equivalent to lead gloves. PMID- 26680549 TI - Evaluation of torsion and twist mechanics of the left ventricle in patients with systemic lupus erythematosus. AB - OBJECTIVE: Myocardial involvement in systemic lupus erythematosus (SLE) has great importance. The aim of this study is to evaluate the rotation and twisting mechanics of the left ventricle (LV) in patients with SLE. METHODS: Forty-three patients fulfilled at least four of the American College of Rheumatology criteria for SLE and 30 individuals as controls were included in the study. SLE disease activity was assessed using the SELENA-SLEDAI score. Echocardiography was performed for all subjects. The patients fulfilled at least four of the American College of Rheumatology criteria for SLE were enrolled in the study. SLE disease activity was assessed using the SELENA-SLEDAI score. Echocardiography was performed for all individuals.Comparisons between groups were made using independent samples t-test with the standard statistical software (SPSS, version 15.0; SPSS Inc., Chicago, IL, USA). Each image was digitally stored for offline analysis. Measurement of global strain assessed by 17-segment model and rotational parameters were performed. LV ejection fraction was calculated by the biplane Simpson's method. Comparisons between groups were made using the independent samples t-test with the standard statistical software. A p value of 0.05 was considered statistically significant. RESULTS: The values of mean global longitudinal strain, basal global circumferential strain (GCS), mean basal radial strain, and apical GCS were significantly lower in SLE patients. The difference between basal rotation, apical rotation, twist of the LV, and torsion of the LV in the SLE patients and controls were not significant (8.8+/-5.5 vs. 10.6+/-5.8, p=0.183;-4.7+/-3.0 vs. -4.8+/-3.2, p=0.947; 11.7+/-6.4 vs. 13.2+/-6.4, p=0.366; and 1.8+/-0.8 vs. 1.9+/-2.3, p=0.725, respectively). Although there was not any significant relationship between SELENA-SLEDAI score and myocardial strain analyses of the LV, the basal rotation and the torsion of the LV were lower in patients with SLE having a SLEDAI score of >=17 (p=0.024 for basal rotation and p=0.032 for torsion). CONCLUSION: The number of segmental and global strain analyses were decreased in SLE patients with globally normal LVEF. The twist and torsion mechanics of the LV were preserved according to the control group, and the left ventricular torsion and basal rotation were found to be significantly decreased in those with an activity score of >=17. PMID- 26680550 TI - Evaluation of atherosclerosis after cessation of cabergoline therapy in patients with prolactinoma. AB - OBJECTIVE: The aim of the study was to determine whether atherosclerotic risk markers exist at the moment and after withdrawal of cabergoline (CAB) therapy in patients who had taken a suitable dose of CAB therapy for a suitable period of time before cessation of CAB. METHODS: This study was designed as prospective cross-sectional. Out of a total of 115 patients with prolactinoma, 42 non-obese women with microprolactinoma, who met the Pituitary Society criteria (2006) for the withdrawal of long-term CAB therapy, and 30 healthy patients participated in our study. The number of patients excluded from the study were as follows: 34 patients with tumor shrinkage of less than 50%; 10 who received DA treatments for less than 2 years; 9 who were treated with bromocriptine; and 20 who had diabetes mellitus, hypertension, hyperlipidemia, obesity, renal disease, coronary arterial disease, or were tobacco smokers. The patients were evaluated for anthropometric, metabolic, and inflammatory parameters at the time of cessation of CAB therapy and at the 3rd and 12th months after the withdrawal of CAB therapy. Endothelial dysfunction was determined by flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), which were assessed by high resolution ultrasonography (USG) by the same practitioner. RESULTS: At the moment of cessation of CAB therapy, the FMD percentage in patients with prolactinoma was worse than that in healthy controls (p=0.0029). After the withdrawal of CAB treatment, fibrinogen (p=0.036), mean platelet volume (MPV) (p<0.001), carotid IMT (p=0.041), and high-density lipoprotein cholesterol (HDL C) (p=0.048) were worse in the relapse patients than those in the remission patients. Furthermore, only MPV values were found to be significantly related to a relapse of hyperprolactinemia among all atherosclerotic risk markers [area under the curve: 0.830 (95% CI 0.685-0.974) (p<0.001)]. CONCLUSION: Unfavorable cardiovascular risk profiles are a problem for patients with prolactinoma during cessation and after CAB withdrawal. PMID- 26680551 TI - Neurally mediated syncope: Is it really an endothelial dysfunction? AB - OBJECTIVE: Syncope is a common problem in children and adolescents. Neurally mediated syncope is the most frequent form of this disorder. Although several studies have evaluated the pathophysiology of neurally mediated syncope, it is still not completely understood. METHODS: We performed a cross-sectional study that included 27 patients aged 5-20 years with unexplained syncope and 30 healthy subjects as a control group. All subjects in both groups were assessed for endothelial function by investigating the following physical and chemical factors: flow-mediated dilation (FMD), intima-media thickness (IMT), circulating vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM)], and endothelial leucocyte adhesion molecule (E-selectin), as well as epinephrine and norepinephrine. The data were statistically analyzed utilizing the SPSS 20.Significant differences between the groups in terms of mean scores were assessed using an independent sample t-test. RESULTS: Mean FMD was significantly higher in the syncope case group than in the control group (p=0.028). There was no significant difference in IMT between the two groups; however, mean levels of ICAM (p=0.02) and VCAM (p=0.008) were significantly higher in the case group than in the control group. The levels of E-selectin also increased in the case group, but not to a statistically significant extent. The mean levels of epinephrine (p=0.01) were significantly lower in the case group than in the control group, and the level of norepinephrine serum decreased slightly, but not significantly, in the syncope patients. CONCLUSION: Our results showed that an endothelial dysfunction or augmented endothelial function might exist in patients with neurally mediated syncope. PMID- 26680552 TI - Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods. AB - BACKGROUND: Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. METHODS: In our previous study, we identified 28 significant proteins- i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. RESULTS: We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. CONCLUSIONS: Combination of systems biology with computer-aided drug design could help us develop novel drug cocktails with multiple targets. We believe this will enhance the efficiency of therapeutic practice and lead to new directions for cancer therapy. PMID- 26680553 TI - Syncope Best Practices: A Syncope Clinical Practice Guideline to Improve Quality. AB - OBJECTIVE: To determine whether implementation of a standardized clinical practice guideline (CPG) for the evaluation of syncope would decrease practice variability and resource utilization. DESIGN: A retrospective review of medical records of patients presenting to our practice for outpatient evaluation of syncope before and after implementation of the CPG. The guideline included elements of history, physical exam, electrocardiogram, and "red flags" for further testing. SETTING: Outpatient pediatric cardiology offices of a large pediatric cardiology practice. PATIENTS: All new patients between 3 and 21 years old, who presented to cardiology clinic with a chief complaint of syncope. INTERVENTIONS: The CPG for the evaluation of pediatric syncope was presented to the providers. OUTCOME MEASURES: Resource utilization was determined by the tests ordered by individual physicians before and after initiation of the CPG. Patient final diagnoses were recorded and the medical records were subsequently reviewed to determine if any patients, who presented again to the system, were ultimately diagnosed with cardiac disease. RESULTS: Of the 1496 patients with an initial visit for syncope, there was no significant difference in the diagnosis of cardiac disease before or after initiation of the CPG: (0.6% vs. 0.4%, P = .55). Electrocardiography provides the highest yield in the evaluation of pediatric syncope. Despite high compliance (86.9%), there were no overall changes in costs ($346.31 vs. $348.53, P = .85) or in resource utilization. There was, however, a decrease in the variability of ordering of echocardiograms among physicians, particularly among those at the extremes of utilization. CONCLUSIONS: Although the CPG did not decrease already low costs, it did decrease the wide variability in echo utilization. Evaluation beyond detailed history, physical exam, and electrocardiography provides no additional benefit in the evaluations of pediatric patients presenting with syncope. PMID- 26680554 TI - Investigation of microRNAs in mouse macrophage responses to lipopolysaccharide stimulation by combining gene expression with microRNA-target information. AB - BACKGROUND: Toll-like receptors, which stimulated by pathogen-associated molecular patterns such as lipopolysaccharides (LPS), induces the releasing of many kinds of proinflammatory cytokines to activate subsequent immune responses. Plenty of studies have also indicated the importance of TLR-signalling on the avoidance of excessive inflammation, tissue repairing and the return to homeostasis after infection and tissue injury. The significance of TLR-signalling attracts many attentions on the regulatory mechanisms since several years ago. However, as newly discovered regulators, how and how many different microRNAs (miRNAs) regulate TLR-signalling pathway are still unclear. RESULTS: By integrating several microarray datasets and miRNA-target information datasets, we identified 431 miRNAs and 498 differentially expressed target genes in bone marrow-derived macrophages (BMDMs) with LPS-stimulation. Cooperative miRNA network were constructed by calculating targets overlap scores, and a sub-network finding algorithm was used to identify cooperative miRNA modules. Finally, 17 and 8 modules are identified in the cooperative miRNA networks composed of miRNAs up regulate and down-regulate genes, respectively. CONCLUSIONS: We used gene expression data of mouse macrophage stimulated by LPS and miRNA-target information to infer the regulatory mechanism of miRNAs on LPS-induced signalling pathway. Also, our results suggest that miRNAs can be important regulators of LPS induced innate immune response in BMDMs. PMID- 26680556 TI - Prevalence and phylogenetic analysis of HTLV-1 in a segregated population in Iran. AB - Human T-lymphotropic virus type 1 (HTLV-1) infection is an important health issue that affects a variety of endemic areas. The Khorasan province, mainly its capital Mashhad in northeastern Iran, was reported to be as one of these endemic regions. Torbat-e Heydarieh, a large city Southwest border to Mashhad with a segregated population was investigated for the prevalence and associated risk factors of HTLV-1 infection in 400 randomly selected individuals. Blood samples were tested for the presence of HTLV-1 antibodies via the ELISA method and then were confirmed by an Immunoblot test. For the presence of HTLV-1 in lymphocytes of infected subjects, PCR was performed on LTR and TAX regions. DNA sequencing of LTR fragment was also carried out to determine the phylogenetic of HTLV-1, using the Maximum likelihood method. HTLV-1 sero-reactivity (sero-prevalence) among the study population was 2% (8/400), of which 1.25% had HTLV-1 provirus in lymphocytes (actual prevalence). HTLV-1 infection was significantly associated with the age, marital status, and history of blood transfusion (P < 0.05). However, there were no statistical differences between HTLV-1 infection, and gender, surgery, and hospitalization. In regression analysis, age showed the most significant correlation with the infection (P = 0.006, OR = 4.33). Based on our phylogenetic study, the HTLV-1 prevalent sequence type of Torbat-e Heydarieh belongs to the cosmopolitan subtype A. HTLV-1 prevalence in Torbat-e Heydarieh (1.25%) is low comparing to those of both Mashhad (2-3%) and Neishabour (3.5-5%) in the province of Khorasan. Thus, traveling mobility and population mixing such as marriage, bureaucratic affairs, occupation, and economic activities could be the usual routs of HTLV-1 new wave of spreading in this segregated city. PMID- 26680557 TI - Kearns-Sayre Syndrome Is a Rare Cause of Diabetes. PMID- 26680555 TI - Negligible uptake and transfer of diet-derived pollen microRNAs in adult honey bees. AB - The putative transfer and gene regulatory activities of diet-derived miRNAs in ingesting animals are still debated. Importantly, no study to date has fully examined the role of dietary uptake of miRNA in the honey bee, a critical pollinator in both agricultural and natural ecosystems. After controlled pollen feeding experiments in adult honey bees, we observed that midguts demonstrated robust increases in plant miRNAs after pollen ingestion. However, we found no evidence of biologically relevant delivery of these molecules to proximal or distal tissues of recipient honey bees. Our results, therefore, support the premise that pollen miRNAs ingested as part of a typical diet are not robustly transferred across barrier epithelia of adult honey bees under normal conditions. Key future questions include whether other small RNA species in honey bee diets behave similarly and whether more specialized and specific delivery mechanisms exist for more efficient transport, particularly in the context of stressed barrier epithelia. PMID- 26680558 TI - Assessment of blood pressure in patients with hypertension aged 60-79 years before and after the publication of the 2014 Eighth Joint National Committee report. AB - OBJECTIVES: In late 2013, the Joint National Committee (JNC 8) published hypertension treatment recommendations endorsing a goal blood pressure (BP) of < 150/90 mmHg starting at age 60 years. This was in contrast to other cardiovascular groups recommending age 80 years for this BP goal. This study examined mean BP in patients from age 60 years to 79 years with hypertension before and after publication of the JNC 8 recommendations. METHODS: This retrospective cohort study examined mean BP and number of antihypertensives for a period of 1 year before and after the release of the JNC 8 report. Patients aged 60-79 years with hypertension receiving care at a University of Colorado Hospital primary care clinic were included. Patients with diabetes, chronic kidney disease, or kidney transplant were excluded. A total of 150 BP measurements were included in each of the before and after time frames. The primary outcomes were change in mean BP and number of antihypertensives. RESULTS: A total of 171 patients met the criteria and were included in the study. Most had BPs in both the before and after time frames. Mean BP values were similar in the before and after groups (130.2/75.9 mmHg versus 131.5/76.6, respectively; p = 0.27/p = 0.46). Mean number of antihypertensives were similar in the before and after groups (1.95 versus 1.93, respectively; p = 0.79). CONCLUSIONS: Over 1 year at an academic health system, new recommendations from the JNC 8 did not affect mean BP or number of antihypertensives in older patients with hypertension. A similar investigation after more time or in patients with newly diagnosed hypertension may help determine the full impact. PMID- 26680559 TI - Percutaneous coronary interventions and antiplatelet therapy in renal transplant recipients. AB - Cardiovascular disease is the leading cause of mortality and morbidity following renal transplantation (RT), accounting for 40-50% of all deaths. After renal transplantation, an adverse cardiovascular event occurs in nearly 40% of patients; given the dialysis vintage and the average wait time, the likelihood of receiving coronary revascularization is very high. There is a significant gap in the literature in terms of the outcomes of prophylactic coronary revascularization in renal transplantation candidates. Current guidelines on myocardial revascularization stipulate that renal transplant patients with significant coronary artery disease (CAD) should not be excluded from the potential benefit of revascularization. Compared with percutaneous coronary intervention (PCI), however, coronary artery bypass grafting is associated with higher early and 30-day mortality. About one-third of renal transplant patients with CAD have to be treated invasively and so PCI is currently the most popular mode of revascularization in these fragile and compromised patients. A newer generation drug-eluting stent (DES) should be preferred over a bare metal stent (BMS) because of its lower risk of restenosis and improved safety concerns (stent thrombosis) compared with first generation DES and BMS. Among DES, despite no significant differences being reported in terms of efficacy, the newer everolimus and zotarolimus eluting stents should be preferred given the possibility of discontinuing, if necessary, dual antiplatelet therapy before 12 months. Since there is a lack of randomized controlled trials, the current guidelines are inadequate to provide a specifically tailored antiplatelet therapeutic approach for renal transplant patients. At present, clopidogrel is the most used agent, confirming its central role in the therapeutic management of renal transplant patients undergoing PCI. While progress in malignancy-related mortality seems a more distant target, a slow but steady reduction in cardiovascular deaths, improving pharmacological and interventional therapy, is nowadays an achievable medium-term target in renal transplant patients. PMID- 26680560 TI - Edoxaban in patients with atrial fibrillation. AB - Edoxaban, a direct factor Xa inhibitor, was extensively studied in the prevention and treatment of venous thromboembolism and in patients with nonvalvular atrial fibrillation (AF). The aim of this review is to focus specifically on the efficacy and safety profile of edoxaban in patients with AF from preclinical development through the phase III trial that led to regulatory approval. PMID- 26680561 TI - Minorities with lupus nephritis and medications: a study of facilitators to medication decision-making. AB - BACKGROUND: Medication decision-making poses a challenge for a significant proportion of patients. This is an even more challenging for patients who have complex, rare, immune conditions that affect them at a young age and are associated with the use of life-long treatment, perceived by some as having significant risk of side effects and toxicity. INTRODUCTION: The aim of our study was to examine the perspectives of women with lupus nephritis on facilitators to medication decision-making. METHODS: We used the nominal group technique (NGT), a structured formative process to elicit patient perspectives. An NGT expert moderated eight patient group meetings. Participants (n = 52) responded to the question "What sorts of things make it easier for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized facilitators to medication decisional processes. RESULTS: Fifty-two women with lupus nephritis participated in eight NGT meetings (27 African-American, 13 Hispanic, and 12 Caucasian). Average age was 40.6 years (standard deviation (SD) = 13.3), and disease duration was 11.8 years (SD = 8.3); 36.5 % obtained at least a college education, and 55.8 % had difficulty in reading health materials. Patients generated 280 decision making facilitators (range of 26 to 42 per panel). Of these, 102 (36 %) facilitators were perceived by patients as having relatively more influence in decision-making processes than others. Prioritized facilitators included effective patient-physician communication regarding benefits/harms, patient desire to live a normal life and improve quality of life, concern for their dependents, experiencing benefits and few/infrequent/no harms with lupus medications, and their affordability. Relative to African-Americans, Caucasian and Hispanic patients endorsed a smaller percentage of facilitators as influential. Level of agreement with which patients within panels independently agreed in their selections of the three most influential facilitators ranged from 33 % to 60 %. CONCLUSIONS: We identified facilitators to lupus medication decision-making. This information will be used to populate a decision aid for lupus nephritis. PMID- 26680563 TI - AUGS 36th Presidential Address: "The Journey of a Thousand Miles Begins With a Single Step" (Lao Tzu). PMID- 26680564 TI - The Impact of Robotic-Assisted Surgery on Training Gynecology Residents. AB - INTRODUCTION: To investigate the changes in surgical route of hysterectomy after implementation of robotics and to assess the impact on the surgical training of gynecology residents. METHODS: This was an institutional review board-approved retrospective analysis at 2 large academic community hospitals. Subjects undergoing hysterectomy during 2005 and 2011 were identified. A stratified random sample representative of the overall number of hysterectomies, 20 per month for each year, was obtained. Charts were reviewed for route of hysterectomy and resident involvement. Chi-square analysis was used for main outcomes. RESULTS: A total of 193 cases from 2005 and 146 cases from 2011 were included. A significant decline in vaginal hysterectomies was noted from 2005 to 2011: 62.2% (n = 120) to 27.4% (n = 40) (P < 0.001). Laparoscopic hysterectomies also declined from 30.1% to 19.9% during the same period (P < 0.026). In addition, although no robotic hysterectomies were performed in 2005, by 2011, this approach accounted for more than one fourth of all such surgeries. Of all cases examined, 40 in 2005 and 45 in 2011 were not attended by a resident. In 2005, 52% (21 of 40) of the uncovered cases were vaginal hysterectomies. However, in 2011, 55% (25 of 45) of the uncovered cases were robotic-assisted and only 11% (5 of 45) were vaginal hysterectomies. CONCLUSIONS: The resultant decline in vaginal and laparoscopic hysterectomies coupled with an additional procedure to master places an increased burden on training programs. Although the impact of the changes on surgical competency is not yet known, our results identify potential areas for focus in training to ensure surgically competent physicians. PMID- 26680565 TI - Anatomic Outcomes of Robotic Assisted Supracervical Hysterectomy and Concurrent Sacrocolpopexy at a Tertiary Care Institution at Initial Adaptation of the Procedure. AB - OBJECTIVE: The aim of the study was to review anatomic and surgical outcomes of robotic-assisted supracervical hysterectomy (RASCH) with concurrent sacrocolpopexy in the treatment of primary pelvic organ prolapse (POP) on initial adaption of this procedure. STUDY DESIGN: A retrospective chart review of patients undergoing RASCH with concurrent sacrocolpopexy between 2009 and 2012 was performed at a tertiary care academic institution, after initial adaption of this procedure. The primary outcome was change in vaginal support (assessed with the pelvic organ prolapse quantification [POP-Q]) at 3 months and 1 year postoperatively. Secondary measures assessed included estimated blood loss, operative times, hospital length of stay, and operative complications. RESULTS: Forty patients (N = 40) underwent RASCH with concurrent sacrocolpopexy. Twenty six patients (65%) had preoperative stage II POP, and 35% had stage III POP. Three months after undergoing the procedure, 55% had achieved stage 0 POP. An additional 35% were categorized as stage I POP. At 1 year, 72.7% were stage I POP or lower. The mean (SD) operating time was 275 (82.3) minutes. Estimated blood loss and mean (SD) length of hospital stay were 163 (114.9) mL and 1.3 (0.8) days, respectively. There were no intensive care unit admissions. The most common postoperative complication was immediate urinary retention in 10% of patients; all cases resolved with time-limited intermittent self-catheterization. CONCLUSIONS: Even with initial adaptation of the procedure, RASCH with concurrent sacrocolpopexy for the repair of primary POP is effective in restoring anatomic support in the short term. Operative complications are minimal. PMID- 26680566 TI - Critical Anatomy Relative to the Sacral Suture: A Postoperative Imaging Study After Robotic Sacrocolpopexy. AB - OBJECTIVE: This study aimed to characterize pertinent anatomy relative to the sacral suture placed at time of robotic sacrocolpopexy using postoperative computed tomography and magnetic resonance imaging. METHODS: A vascular clip was placed at the base of the sacral suture at the time of robotic sacrocolpopexy. Six weeks postoperatively, subjects returned for a computed tomography scan and magnetic resonance imaging. RESULTS: Ten subjects completed the study. The middle sacral artery and vein coursed midline or to the left of midline in all the subjects. The left common iliac vein was an average of 26 mm from the sacral suture. To the right of the suture, the right common iliac artery was 18 mm away. Following the right common iliac artery to its bifurcation, the right internal iliac was on average 10 mm from the suture. The bifurcations of the inferior vena cava and the aorta were 33 mm and 54 mm further cephalad, respectively.The right ureter, on average, was 18 mm from the suture. The thickness of the anterior longitudinal ligament was 2 mm.The mean angle of descent of the sacrum was 70 degrees. Lastly, we found that 70% of the time, a vertebral body was directly below the suture; the disc was noted in 30%. CONCLUSIONS: We describe critical anatomy surrounding the sacral suture placed during robotic sacrocolpopexy. Proximity of both vascular and urologic structures within 10 to 18 mm, as well as anterior ligament thickness of only 2 mm highlights the importance of adequate exposure, careful dissection, and surgeon expertise. PMID- 26680567 TI - Comparison of clinical cut-points and treatment targets for urine NTX and plasma betaCTX-I in osteoporosis. AB - OBJECTIVE: We undertook to identify levels for plasma beta isomerised carboxy terminal telopeptides of type I collagen (p-betaCTX-I) that are comparable to currently used urine amino-terminal telopeptides of type I collagen (u-NTX) cut points and treatment targets in osteoporosis. DESIGN AND METHODS: Fasting morning samples were collected from patients attending tertiary hospitals and clinics for investigation of metabolic bone disease. Patients with Paget's disease or <20years of age were excluded. Second void spot urine for NTX and plasma (EDTA) samples were utilised. Urine was analysed routinely and plasma stored at -20C until analysis by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. The relationship of u-NTX with each p-betaCTX-I method's results was assessed by Passing and Bablok regression, and p-betaCTX-I levels equivalent to u-NTX cut-points and targets were interpolated. RESULTS: One hundred and forty six patients were included. Spearman correlation coefficients ranged from 0.71 to 0.75 for the three betaCTX-I assays. The equivalent betaCTX-I concentrations for NTX/Cr values of 21 (fracture risk reduction target following risedronate therapy), 27 (healthy pre-menopausal women's mean value), and 38 (threshold for reduction of BMD on calcium alone) nmol BCE/mmol were 230, 312 and 462ng/L for the automated Roche assay and 271, 395 and 624ng/L for the automated IDS i-SYS assay respectively. CONCLUSIONS: The p-betaCTX-I equivalent to the only available fracture outcome based absolute treatment threshold of 21nmol BCE/mmol established for u-NTX, is close to 250ng/L but will vary between p-betaCTX-I assays. PMID- 26680570 TI - Normal Variation in Pubertal Timing: Genetic Determinants in Relation to Growth and Adiposity. AB - In humans, there is a considerable variation in age of onset of puberty. Twin studies have indicated that pubertal timing is a highly heritable trait. Recently, a few rare genetic causes of precocious puberty have been reported as well as genetic mutations associated with isolated hypogonadotropic hypogonadism. Genome-wide association (GWA) studies have helped to explore the genetic determinants of the normal variation in pubertal timing, but have been able to explain only 2.7% of the variance in age at menarche, highlighting the involvement of multiple genes with small effect sizes. These studies indicate an overlap of genes involved in pubertal timing and adiposity, and epidemiological data suggest the existence of a pathway of early infancy weight gain, increased height gain in childhood, earlier pubertal timing and increased adiposity in adulthood. This chapter summarises the data from GWA and epidemiological studies on the normal variation in pubertal timing in relation to growth and adiposity. We discuss putative mechanisms linking early life events to pubertal timing, potential short-term and life-course consequences of earlier pubertal timing, and the impact of these data on clinical management of pubertal disorders. PMID- 26680569 TI - The Emerging Role of Epigenetics in the Regulation of Female Puberty. AB - In recent years the pace of discovering the molecular and genetic underpinnings of the pubertal process has accelerated considerably. Genes required for human puberty to occur have been identified and evidence has been provided suggesting that the initiation of puberty requires coordinated changes in the output of a multiplicity of genes organized into functional networks. Recent evidence suggests that a dual mechanism of epigenetic regulation affecting the transcriptional activity of neurons involved in stimulating gonadotropin releasing hormone release plays a fundamental role in the timing of puberty. The Polycomb group (PcG) of transcriptional silencers appears to be a major component of the repressive arm of this mechanism. PcG proteins prevent the premature initiation of female puberty by silencing the Kiss1 gene in kisspeptin neurons of the arcuate nucleus (ARC) of the hypothalamus. Because the abundance of histone marks either catalyzed by--or associated with--the Trithorax group (TrxG) of transcriptional activators increases at the time when PcG control subsides, it appears that the TrxG complex is the counteracting partner of PcG-mediated gene silencing. In this chapter, we discuss the concept that a switch from epigenetic repression to activation within ARC kisspeptin neurons is a core mechanism underlying the initiation of female puberty. PMID- 26680571 TI - Genetics of Hypogonadotropic Hypogonadism. AB - Hypogonadotropic hypogonadism (HH) often manifests as pubertal delay. A considerable proportion of cases of HH is due to genetic mutations. Recognizing those mutated genes and associated phenotypes may improve our diagnostic capabilities. GNRHR and TACR3 should be the first two genes to be screened in a clinical setting for equivocal cases such as constitutional delay in puberty versus idiopathic HH. In Kallmann syndrome (KS), according to the presence of certain accompanying clinical features, genetic screening for particular gene(s) may be prioritized: synkinesia (KAL1), dental agenesis (FGF8/FGFR1), bony anomalies (FGF8/FGFR1), and hearing loss (CHD7, SOX10). FEZF1 has recently been added to the growing list of KS genes. Also, discovery of mutations in KISS1/KISS1R and TAC3/TACR3 in kisspeptin and neurokinin B signaling, respectively, has provided major advancements in our understanding of the biology of the gonadotropin-releasing hormone pulse generator. Identification of further causative mutations accounting for the HH phenotype, which is now more feasible with the increasing popularity of whole exome sequencing, may provide deeper insight into the biology of the hypothalamic-pituitary-gonadal axis. PMID- 26680572 TI - Sexual Precocity--Genetic Bases of Central Precocious Puberty and Autonomous Gonadal Activation. AB - Precocious puberty has been classically defined as the onset of sexual secondary characteristics in girls younger than 8 years and in boys younger than 9 years. The discovery of potential factors which trigger human puberty is one of the central mysteries of reproductive biology. Several approaches, including mutational analysis of candidate genes, large-scale genome-wide association studies, and (more recently) whole-exome sequencing, have been performed in attempt to identify novel genetic factors that modulate the human hypothalamic pituitary-gonadal axis, resulting in premature sexual development. In the last two decades, it has been well established that autonomous gonadal activation can be caused by somatic (GNAS) or germline (LHCGR)-activating mutations of genes that encode essential elements for signal transduction of G protein-coupled receptors, resulting in peripheral precocious puberty in McCune-Albright syndrome and testotoxicosis, respectively. More recently, dominant activating and inactivating mutations of excitatory (KISS1/KISS1R) and inhibitory (MKRN3) modulators of gonadotropin-releasing hormone secretion, respectively, were associated with central precocious puberty phenotype. Indeed, loss-of-function mutations of MKRN3, a maternal imprinted gene located at chromosome 15q, currently represent a frequent cause of central precocious puberty diagnosed in families from distinct geographic origins. Here, we review the known genetic defects in central and peripheral precocious puberty. PMID- 26680573 TI - Congenital Hypogonadotropic Hypogonadism: A Trait Shared by Several Complex Neurodevelopmental Disorders. AB - Reproductive function depends on the activity of the gonadotropic axis, which is controlled by a hypothalamic neural network whose main function is to regulate the secretion of gonadotropin-releasing hormone (GnRH). This endocrine network is not mature at birth, and several phases of activation-inactivation of the gonadotropic axis are necessary for its normal development. The postnatal maturation of the GnRH network lies under the control of a neurodevelopmental program that starts in fetal life and ends at puberty. There are many clinical situations in which this program is interrupted, leading to congenital hypogonadotropic hypogonadism (CHH) and an absence of puberty. For many years, attention has mainly been focused on the genetics of isolated CHH. More recently, the emergence of new genomics techniques has led to the description of genetic defects in very rare syndromes in which CHH is associated with complex neurological dysfunctions. Here, we review the clinical phenotype and genetic defects linked to such syndromic CHH. This analysis highlights the close link between the ubiquitin pathway, synaptic proteins and CHH, as well as unexpected mutations in genes encoding nucleolar proteins. PMID- 26680574 TI - Animal Modeling of Early Programming and Disruption of Pubertal Maturation. AB - Puberty is a fascinating developmental transition that gates the attainment of reproductive capacity and culminates the somatic and sexual maturation of the organism. Rather than a circumscribed phenomenon, puberty is the endpoint of a long-lasting developmental continuum, which initiates in utero. Besides important genetic determinants, the tempo of puberty is influenced by numerous endogenous and exogenous factors that, acting at different levels of the developing hypothalamic-pituitary-gonadal (HPG) axis along the maturational continuum indicated above, can influence puberty onset. Among the different modifiers of puberty, in this chapter we will focus our attention on two major groups of signals, sex steroids and nutritional cues, and how these interplay mostly with the central elements of the HPG axis, and especially with gonadotropin-releasing hormone neurons and their key upstream afferents, Kiss1 neurons, to influence the timing of puberty. Special emphasis will be given to summarize information emerging from relevant preclinical (mostly rodent) animal models, and how this information might be relevant in terms of translational medicine, as it may help for a better understanding and eventually management of pubertal disorders of escalating prevalence worldwide. PMID- 26680575 TI - Contemporary Trends in Onset and Completion of Puberty, Gain in Height and Adiposity. AB - Recent studies have documented earlier pubertal maturation in both girls and boys. Several factors have been proposed to account for earlier maturation. Epidemiologic studies have indicated that genetic factors are the most important influence contributing to the variability in the onset of puberty. Studies have also noted the association of elevated BMI with earlier puberty in girls, although the relationship between BMI and onset of puberty in boys is less consistent. The relationship of BMI and onset of puberty may be mediated by several factors, including leptin and kisspeptin, changes in bioavailable sex hormones, and environmental exposures. Recently, there have been genome-wide meta analyses examining onset of puberty and anthropometric traits that may provide insight into the relationships of BMI, height velocity, and pubertal timing. Newer fields of investigation include examination of epigenetic modification. PMID- 26680576 TI - Consequences of Early Life Programing by Genetic and Environmental Influences: A Synthesis Regarding Pubertal Timing. AB - Sexual maturation is closely tied to growth and body weight gain, suggesting that regulative metabolic pathways are shared between somatic and pubertal development. The pre- and postnatal environment affects both growth and pubertal development, indicating that common pathways are affected by the environment. Intrauterine and early infantile developmental phases are characterized by high plasticity and thereby susceptibility to factors that affect metabolic function as well as related reproductive function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, causing rapid weight gain with the risk for adult disease and premature onset of puberty. Environmental factors can cause modifications to the genome, so-called epigenetic changes, to affect gene expression and subsequently modify phenotypic expression of genomic information. Epigenetic modifications, which occur in children born small for gestational age, are thought to underlie part of the metabolic programming that subsequently effects both somatic and pubertal development. PMID- 26680577 TI - Nutritional and Pubertal Disorders. AB - Caloric-protein malnutrition can slow growth and cause pubertal delay. This chapter focuses on endocrine abnormalities and pubertal alterations in patients with eating disorders, childhood obesity, the female athlete triad and children cancer survivors. Patients with anorexia nervosa (AN) exhibit multiple endocrine abnormalities, including isolated hypogonadotropic hypogonadism. The delay in pubertal development and reduction in growth seen in AN patients may be a direct result of malnutrition. Appropriate psychiatric, nutritional and hormonal therapy is necessary. It is suggested that obesity during childhood can accelerate pubertal onset and these children usually exhibit accelerated linear growth during puberty. In girls the relationship between childhood obesity and early pubertal onset could be related to their insulin resistance and/or hyperinsulinemia. The female athlete triad is often observed in physically active girls and women in whom low energy availability with or without disordered eating, menstrual dysfunction and low bone mineral density can be present. In prepubertal girls excess exercise can cause delayed menarche with no effects on adult height, while in postpubertal females it results in menstrual cycle irregularities. The consequences of childhood cancer depend on the type of cancer, its location, the age at which the disease was diagnosed, the dose of radiotherapy, and the type and dose of chemotherapy. PMID- 26680578 TI - Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors. AB - The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle. PMID- 26680579 TI - Sex Steroid and Gonadotropin Treatment in Male Delayed Puberty. AB - Male delayed puberty is common, affecting up to 3% of the population. Management of patients with pubertal delay is dependent on the underlying cause. The main differential diagnoses of delayed puberty in males include constitutional delay of growth and puberty (CDGP), idiopathic hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. Treatment of isolated CDGP involves expectant observation or short courses of low-dose sex steroid supplementation. More complex and involved management is required in males with hypogonadism to achieve both development of secondary sexual characteristics and to maximise the potential for fertility. This review will cover the options for management involving androgen or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatment options. PMID- 26680580 TI - Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood. AB - The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 ug/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated. PMID- 26680581 TI - Gonadotropin-Releasing Hormone Agonist Treatment in Sexual Precocity. AB - Depot gonadotropin-releasing hormone (GnRH) analogs represent the first-line therapy in sexual precocity due to central precocious puberty. GnRH analogs desensitize the pituitary and account for the suppression of luteinizing hormone and follicle-stimulating hormone leading to a decrease of sex steroid levels. The conventional indications are central puberty starting before the age of 8 years in girls and 9 years in boys. These indications can be extended to difficult conditions with poor adult height prognosis or marked psychosocial impact. This includes children after irradiation, international adoption, and children with a physical handicap or mental disabilities. There are different formulations of depot preparations of GnRH analogs; long-acting 1- or 3-month forms are widely used in Europe and all are well tolerated with minor side effects. Overweight is often present at the onset of precocious puberty and some etiologies such as hamartomas predispose to obesity, requiring appropriate care for weight control during and after the cessation of GnRH analog treatment. Many studies have reported on the effects on adult height, which seems to be especially beneficial when treatment is started before the age of 6; however, few studies have focused on the establishment of the 1st menstruation, 1st sexual intercourse, socioprofessional outcome and subsequent fertility. PMID- 26680582 TI - Treatment of Peripheral Precocious Puberty. AB - There are many etiologies of peripheral precocious puberty (PPP) with diverse manifestations resulting from exposure to androgens, estrogens, or both. The clinical presentation depends on the underlying process and may be acute or gradual. The primary goals of therapy are to halt pubertal development and restore sex steroids to prepubertal values. Attenuation of linear growth velocity and rate of skeletal maturation in order to maximize height potential are additional considerations for many patients. McCune-Albright syndrome (MAS) and familial male-limited precocious puberty (FMPP) represent rare causes of PPP that arise from activating mutations in GNAS1 and the LH receptor gene, respectively. Several different therapeutic approaches have been investigated for both conditions with variable success. Experience to date suggests that the ideal therapy for precocious puberty secondary to MAS in girls remains elusive. In contrast, while the number of treated patients remains small, several successful therapeutic options for FMPP are available. PMID- 26680583 TI - Consultation for Disordered Puberty: What Do Adolescent Medicine Patients Teach Us? AB - The period of adolescence is not only marked by important growth and pubertal events, but is also characterized by important psychosocial changes driven by a search for autonomy and the construction of one's identity. It can thus be easily understood that puberty disorders interfere heavily with these process, requiring from the endocrinologist not only medical knowledge, but also a great deal of emotional and psychological skills. They must progressively move from an educational approach that heavily involves the parents to one of shared information and decision making that places the young patient at the center of the therapeutic process. This can be achieved in several ways: respecting the affective and cognitive development of the adolescent; securing his privacy and (if requested by him) confidentiality; exploring his self-image and self-esteem and adapting the therapeutic process to the patient's expectations; reviewing the teenager's lifestyle, including the issue of sexuality and sexual behavior, and involving him in any therapeutic choice that has to be made, even if it does not match with the parents' expectations. The skills required for this respectful and holistic follow-up often exceed the abilities of any physician; it is thus suggested that a team approach involving a clinical nurse and/or a psychologist and/or social worker(s) be set up whenever possible. PMID- 26680584 TI - A Safety Evaluation of Cangrelor in Patients Undergoing PCI. AB - INTRODUCTION: Dual antiplatelet therapy with aspirin and an oral ADP P2Y12 receptor antagonist is the standard-of-care for treatment of patients undergoing percutaneous coronary intervention (PCI). However, oral P2Y12 receptor antagonists have several limitations, including inter- and intra-individual response variability, drug-drug interactions, slow onset and offset of action and delayed platelet inhibition in high-risk clinical settings, such as patients with ST-segment elevation myocardial infarction. AREAS COVERED: Cangrelor is an intravenous, direct-acting, reversible, potent P2Y12 receptor antagonist. It rapidly achieves near complete platelet inhibition and has a very short half-life and a fast offset of action. We conducted a systematic review searching PubMed/MEDLINE for pharmacodynamic/pharmacokinetic studies and clinical trials in which cangrelor was investigated, published from any time up to November 1(st) 2015. For clinical trials, those investigating cangrelor in the setting of PCI were considered for discussion. EXPERT OPINION: Cangrelor is approved by drug regulating authorities worldwide as adjunctive antithrombotic therapy for the full spectrum of patients undergoing PCI, not pre-treated with a P2Y12 receptor inhibitor and not with intent to receive a glycoprotein IIb/IIIa inhibitor. Its unique pharmacological properties and its favorable safety and efficacy profile make it an attractive treatment strategy, especially in clinical settings where immediate platelet inhibition is required. PMID- 26680586 TI - The Physio-Pharmacological Role of the NPS/NPSR System in Psychiatric Disorders: A Translational Overview. AB - In 2004, Neuropeptide S (NPS) was identified to be the cognate ligand of the previously discovered orphan receptor GPCR 154, now termed as NPS receptor (NPSR). Since, then a wealth of data has elucidated the unique behavioral profile of this peptidergic system in numerous physiological function such as being pro arousal and anxiolytic at the same time. Besides, its robust anxiolytic profile, this peptide system has been found to activate HPA axis and concomitant release of ACTH and corticosterone. Additionally, the involvement of NPS in reinstatement of drug seeking behavior has also been reported. In recent years, accumulating data from various labs have demonstrated an A/T single-nucleotide polymorphism (SNP) resulting in (Asn107Ile) switch in the human NPSR gene as the risk factor for various psychiatric disorders such as panic disorder, post traumatic syndrome, alcohol use disorders and enhanced anxiety sensitivity, although, this is in stark contrast to the findings made in animal models which have consistently projected the anxiolytic nature of this peptide system. Therefore, in context of robust involvement of NPS system in various psychiatric disorders this review article considers the importance of NPS from translational point of view and appraises the need of therapies to be tailored around NPSR. In this respect, pharmacology of important NPSR ligands which have been recently developed has been discussed together with their possible side effects profile. Additionally, this review article encompasses all recent developments in the field of NPS system highlighting the role of this neuropeptide in all those biological functions which are modulated by this system. The role of this peptide has been discussed in detail in the perspective of sleep regulation, anxiety, fear expression and most importantly in drug addiction. Additionally, neuroimaging and genetic linkage studies addressing the functional impact of NPSR1 variants in the aforementioned psychiatric disorders have also been discussed. PMID- 26680587 TI - A systems pharmacology approach to decipher the mechanism of danggui-shaoyao-san decoction for the treatment of neurodegenerative diseases. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Neurodegenerative diseases (NDs) is a time dependent course for a sequence of conditions that primarily impact the neurons in the human brain, ultimately, resulting in persistence and progressive degeneration and / or death of nerve cells and reduction of cognition and memory function. Currently, there are no therapeutic approaches to cure neurodegeneration, except certain medicines that temporarily alleviate symptoms, facilitating the improvement of a patients' quality of life. Danggui-shaoyao-san (DSS), as a famous Chinese herbal formula, has been widely used in the treatment of various illnesses, including neurodegenerative diseases. Although well practiced in clinical medicine, the mechanisms involved in DSS for the treatment of neurodegenerative diseases remain elusive. MATERIALS AND METHODS: In the present study, a novel systems pharmacology approach was developed to decipher the potential mechanism between DSS and neurodegenerative disorders, implicated in oral bioavailability screening, drug-likeness assessment, target identification and network analysis. RESULTS: Based on a comprehensive systems approach, active compounds of DSS, relevant potential targets and targets associated with diseases were predicted. Active compounds, targets and diseases were used to construct biological networks, such as, compound-target interactions and target-disease networks, to decipher the mechanisms of DSS to address NDs. CONCLUSIONS: Overall, a well-understood picture of DSS, hallmarked by multiple herbs-compounds-targets-pathway-cooperation networks for the treatment of NDs, was revealed. Notably, this systems pharmacology approach provided a novel in silico approach for the development paradigm of traditional Chinese medicine (TCM) and the generation of new strategies for the management of NDs. PMID- 26680585 TI - ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-beta-Induced Smad Activation. AB - Epithelial-mesenchymal transition (EMT) is a normal cell differentiation event during development and contributes pathologically to carcinoma and fibrosis progression. EMT often associates with increased transforming growth factor-beta (TGF-beta) signaling, and TGF-beta drives EMT, in part through Smad-mediated reprogramming of gene expression. TGF-beta also activates the Erk MAPK pathway through recruitment and Tyr phosphorylation of the adaptor protein ShcA by the activated TGF-beta type I receptor. We found that ShcA protects the epithelial integrity of nontransformed cells against EMT by repressing TGF-beta-induced, Smad-mediated gene expression. p52ShcA competed with Smad3 for TGF-beta receptor binding, and down-regulation of ShcA expression enhanced autocrine TGF-beta/Smad signaling and target gene expression, whereas increased p52ShcA expression resulted in decreased Smad3 binding to the TGF-beta receptor, decreased Smad3 activation, and increased Erk MAPK and Akt signaling. Furthermore, p52ShcA sequestered TGF-beta receptor complexes to caveolin-associated membrane compartments, and reducing ShcA expression enhanced the receptor localization in clathrin-associated membrane compartments that enable Smad activation. Consequently, silencing ShcA expression induced EMT, with increased cell migration, invasion, and dissemination, and increased stem cell generation and mammosphere formation, dependent upon autocrine TGF-beta signaling. These findings position ShcA as a determinant of the epithelial phenotype by repressing TGF-beta-induced Smad activation through differential partitioning of receptor complexes at the cell surface. PMID- 26680588 TI - Quantitative genotoxicity assays for analysis of medicinal plants: A systematic review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are known to contain numerous biologically active compounds, and although they have proven pharmacological properties, they can cause harm, including DNA damage. AIM OF THE STUDY: Review the literature to evaluate the genotoxicity risk of medicinal plants, explore the genotoxicity assays most used and compare these to the current legal requirements. MATERIAL AND METHODS: A quantitative systematic review of the literature, using the keywords "medicinal plants", "genotoxicity" and "mutagenicity", was undertakenQ to identify the types of assays most used to assess genotoxicity, and to evaluate the genotoxicity potential of medicinal plant extracts. RESULTS: The database searches retrieved 2289 records, 458 of which met the inclusion criteria. Evaluation of the selected articles showed a total of 24 different assays used for an assessment of medicinal plant extract genotoxicity. More than a quarter of those studies (28.4%) reported positive results for genotoxicity. CONCLUSIONS: This review demonstrates that a range of genotoxicity assay methods are used to evaluate the genotoxicity potential of medicinal plant extracts. The most used methods are those recommended by regulatory agencies. However, based on the current findings, in order to conduct a thorough study concerning the possible genotoxic effects of a medicinal plant, we indicate that it is important always to include bacterial and mammalian tests, with at least one in vivo assay. Also, these tests should be capable of detecting outcomes that include mutation induction, clastogenic and aneugenic effects, and structural chromosome abnormalities. In addition, the considerable rate of positive results detected in this analysis further supports the relevance of assessing the genotoxicity potential of medicinal plants. PMID- 26680590 TI - Advances in clinical next-generation sequencing: target enrichment and sequencing technologies. AB - The huge parallel sequencing capabilities of next generation sequencing technologies have made them the tools of choice to characterize genomic aberrations for research and diagnostic purposes. For clinical applications, screening the whole genome or exome is challenging owing to the large genomic area to be sequenced, associated costs, complexity of data, and lack of known clinical significance of all genes. Consequently, routine screening involves limited markers with established clinical relevance. This process, referred to as targeted genome sequencing, requires selective enrichment of the genomic areas comprising these markers via one of several primer or probe-based enrichment strategies, followed by sequencing of the enriched genomic areas. Here, the authors review current target enrichment approaches and next generation sequencing platforms, focusing on the underlying principles, capabilities, and limitations of each technology along with validation and implementation for clinical testing. PMID- 26680589 TI - Ethnomedical research and review of Q'eqchi Maya women's reproductive health in the Lake Izabal region of Guatemala: Past, present and future prospects. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In Central America, most Maya women use ethnomedicines for all aspects of their reproductive cycle including menstruation, pregnancy and menopause. However, very few of these plants have been documented, collected and tested in appropriate pharmacological assays to determine possible safety and efficacy. The aim of this work was to provide an overview of information on the ethnomedical uses, ethnopharmacology, chemistry and pharmacological research for medicinal plants used for women's reproductive health in Guatemala, with a special emphasis on the Q'eqchi Maya of the Lake Izabal region, to demonstrate therapeutic potential and support future research in the field. MATERIALS AND METHODS: Reviews of the ethnobotanical, ethnomedical and ethnopharmacological literature were performed for 30 plants collected in the Lake Izabal region of Guatemala and used by the Q'eqchi Maya for treatment of reproductive health issues were performed up to and including July 2015 using multiple databases, library searches for abstracts, books, dissertations, and websites. RESULTS AND CONCLUSIONS: Review of the published research confirms that many of the plants used by Q'eqchi Maya women for the management of reproductive health issues have pharmacological activities, including analgesic, anti inflammatory, estrogenic, progestagenic and/or serotonergic effects, that support the use of these plants and provide plausible mechanisms of action for their traditional uses. Furthermore, a new serotonin agonist, 9, 10-methylenedioxy-5, 6 Z-fadyenolide was isolated, thereby demonstrating an untapped potential for drug discovery. However, to date much of the pharmacological assays have been in vitro only, and few in vivo studies have been performed. Considering the large percentage of the Maya population in Guatemala that use traditional medicines, there remains a significant lack of pharmacological and toxicological data for these plants. Future research should focus on the safety and efficacy of medicinal plants using in vivo preclinical studies and clinical trials, as well as chemical analysis. Since medicinal plants from the Piperaceae are most commonly used as traditional medicines by the Q'eqchi Maya women, and new bioactive compounds have been identified from Piper species, investigations of commonly used plants from this family would be an appropriate place to start. Data generated from such studies would contribute to Guatemala's national effort to promote a complementary relationship between traditional Maya medicine and public health services. PMID- 26680592 TI - A high-throughput method for measurement of glycohemoglobin in blood samples utilizing laser-accelerated proteolysis and MALDI-TOF MS. AB - Glycosylated hemoglobin A1c (HbA1c) is a useful marker for the diagnosis of diabetes mellitus. Commercial column separation methods for HbA1c measurement were lacking throughput and sometimes interfered with hemoglobin variants. In this work, we developed a high-throughput and specific method for HbA1c by quantitative measurement of N-terminal peptides (NT method). Two thousand specimens could be measured in 8 h. The high-throughput was achieved by using a fast analysis of matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) and an efficient proteolysis accelerated by laser irradiation. An intensity ratio of glycosylated to non-glycosylated hemoglobin N terminal peptides was used to calculate the HbA1c level in blood. Interference from Hb variants of N-terminal peptides could be excluded by a highly accurate mass selection. The coefficient of variation (CV) of intra-assay precision was 9.8 and 9.9%, respectively. The CVs of inter-assay precision over 20 days were 9.1 and 8.4%, respectively. Measurement results were well correlated with the commercially available column method (r = 0.995). The NT method is promising for large-scale screening for diabetes mellitus among people. PMID- 26680591 TI - Developing and Integrating Advanced Movement Features Improves Automated Classification of Ciliate Species. AB - Recent advances in tracking technologies such as GPS or video tracking systems describe the movement paths of individuals in unprecedented details and are increasingly used in different fields, including ecology. However, extracting information from raw movement data requires advanced analysis techniques, for instance to infer behaviors expressed during a certain period of the recorded trajectory, or gender or species identity in case data is obtained from remote tracking. In this paper, we address how different movement features affect the ability to automatically classify the species identity, using a dataset of unicellular microbes (i.e., ciliates). Previously, morphological attributes and simple movement metrics, such as speed, were used for classifying ciliate species. Here, we demonstrate that adding advanced movement features, in particular such based on discrete wavelet transform, to morphological features can improve classification. These results may have practical applications in automated monitoring of waste water facilities as well as environmental monitoring of aquatic systems. PMID- 26680593 TI - Determination of cathinones and other stimulant, psychedelic, and dissociative designer drugs in real hair samples. AB - The detection of new psychoactive substances (NPS) in hair proved to provide insight into their current diffusion among the population and the social characteristics of these synthetic drugs' users. Therefore, a UHPLC-MS/MS method was developed in order to determine 31 stimulant and psychedelic substituted phenethylamines, and dissociative drugs in hair samples. The method proved to be simple, fast, specific, and sensitive. The absence of matrix interferents, together with excellent repeatability of both retention times and relative abundances of diagnostic transitions, allowed the correct identification of all analytes tested. The method showed optimal linearity in the interval 10-1000 pg/mg, with correlation coefficient values varying between 0.9981 and 0.9997. Quantitation limits ranged from 1.8 pg/mg for 4-methoxyphencyclidine (4-MeO-PCP) up to 35 pg/mg for 6-(2-aminopropyl)benzofuran (6-APB). The method was applied to (i) 23 real samples taken from proven MDMA and ketamine abusers and (ii) 54 real hair samples which had been previously tested negative during regular drug screening in driver's license recovery. Six samples tested positive for at least one target analyte. Methoxetamine (MXE) was found in three cases (range of concentration 7.7-27 pg/mg); mephedrone (4-MMC) was found in two cases (50-59 pg/mg) while one sample tested positive for methylone at 28 pg/mg. Other positive findings included 4-methylethcathinone (4-MEC), alpha-pyrrolidinovalerophenone (alpha-PVP), 4-fluoroamphetamine (4-FA), 3,4-methylenedioxypyrovalerone (MDPV), and diphenidine. The present study confirms the increasing diffusion of new designer drugs with enhanced stimulant activity among the target population of poly-abuse consumers. PMID- 26680594 TI - The Nurses' Well-Being Index and Factors Influencing This Index among Nurses in Central China: A Cross-Sectional Study. AB - BACKGROUNDS/OBJECTIVES: A discussion and analysis of factors that contribute to nurses' happiness index can be useful in developing effective interventions to improve nurses' enthusiasm, sense of honor and pride and to improve the efficiency and quality of medical services. METHODS: In this study, 206 registered nurses at the 2011 annual encounter for 12 Hanchuan hospitals completed a questionnaire survey that covered three aspects of the well-being index and thus served as a comprehensive well-being and general information tool. RESULTS: Based on their index score, the nurses' overall happiness level was moderate. The dimensions of the happiness index are listed in descending order of their contribution to the nurses' comprehensive happiness levels: health concerns, friendly relationships, self-worth, altruism, vitality, positive emotions, personality development, life satisfaction and negative emotions. Four variables (positive emotion, life satisfaction, negative emotions, and friendly relationships) jointly explained 47.80% of the total variance of the happiness index; positive emotions had the greatest impact on the happiness index. CONCLUSIONS: Appropriate nursing interventions can improve nurses' happiness index scores, thereby increasing nurses' motivation and promoting the development of their nursing practice. PMID- 26680595 TI - Predictors of Depression Symptoms Among Low-Income Women Exposed to Perinatal Intimate Partner Violence (IPV). AB - Women experiencing perinatal intimate partner violence (IPV) may be at increased risk for depression. Baseline data was analyzed from 239 low-income pregnant women participating in an intervention study designed to reduce exposure to IPV. Depression risk was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and IPV factors were measured with the Conflict Tactics Scale-Revised (CTS 2). Stepwise regression was conducted to identify predictors of risk for depression. Race (p = 0.028), psychological IPV (p = 0.035) and sexual IPV (p = 0.031) were strongly associated with risk for depression. Regression results indicated that women experiencing severe psychological IPV were more likely to develop depression (OR 3.16, 95 % CI 1.246, 8.013) than those experiencing severe physical or sexual IPV. Experiencing severe psychological IPV during pregnancy is strongly linked to risk for depression. Routine screening for psychological IPV may increase identification and treatment of women at high risk for depression during pregnancy. PMID- 26680596 TI - Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism. AB - PURPOSE: Urolithins, metabolites produced by the gut microbiota from ellagic acid, have been acknowledged with cancer chemopreventive activity. Although urolithin A (Uro-A) has been reported to be the most active one, 10-50 % of humans can also produce the isomer isourolithin A (IsoUro-A). However, no biological activity for IsoUro-A has been reported so far. Herein, we describe for the first time the antiproliferative effect of IsoUro-A, compared to Uro-A, against both human colon cancer (Caco-2) and normal (CCD18-Co) cell lines. METHODS: Cell proliferation was evaluated by MTT and Trypan blue exclusion assays. Cell cycle was analyzed by flow cytometry and apoptosis measured by the Annexin V/PI method. Finally, urolithins metabolism was analyzed by HPLC-DAD MS/MS. RESULTS: IsoUro-A inhibited the proliferation of Caco-2 cells in a time- and dose-dependent manner, though it was significantly lower than Uro-A (IC50 = 69.7 +/- 4.5 and 49.2 +/- 3.8 MUM at 48 h, respectively). Both urolithins arrested Caco-2 cell cycle at S and G2/M phases and induced apoptosis at concentrations previously found in human colon tissues. Notably, Caco-2 cells glucuronidated more efficiently IsoUro-A than Uro-A (~50 vs. ~20 % of conversion after 48 h, respectively). Both Uro-A and IsoUro-A glucuronides did not exert antiproliferative effects. In addition, cell growth inhibition was higher in Caco 2 than in normal cells. CONCLUSIONS: IsoUro-A exerts strong antiproliferative activity, which is reduced by the extensive glucuronidation at 9-position in cancer cells. Further studies are needed to elucidate whether the in vitro structure-activity relationship found for Uro-A and IsoUro-A plays any role in humans. PMID- 26680598 TI - Guidelines can require me to recommend care that I think is wrong. PMID- 26680597 TI - Metabolic syndrome and selenium during gestation and lactation. AB - PURPOSE: Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. METHOD: Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. RESULTS: Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. CONCLUSION: With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS. PMID- 26680599 TI - Depressive symptoms increase the risk of progression to dementia in subjects with mild cognitive impairment: systematic review and meta-analysis. AB - OBJECTIVE: There is a long-standing debate in the literature whether depressive symptoms increase the risk of dementia in older with mild cognitive impairment (MCI). We aim to conduct a meta-analysis of studies that evaluated the risk of dementia in subjects with MCI and depressive symptoms compared with subjects with MCI and no depressive symptoms. METHODS: We calculated the relative risk of progression to dementia in subjects with MCI and depressive symptoms compared with subjects with MCI and no depressive symptoms using a generic inverse variance method with random effect models. RESULTS: Eighteen studies were included in the meta-analysis, with a sample size of 10,861 MCI subjects. The pooled relative risk of progressing to dementia was 1.28 CI95% [1.09-1.52] (p = 0.003) in the group of MCI subjects with depressive symptoms compared with the MCI subjects with no depressive symptoms. DISCUSSION: Our results provide additional evidence that depressive symptoms determine an additive risk effect to the progression to dementia in subjects with MCI. The comorbidity between depression and cognitive impairment can be an intervention target for prevention of dementia in MCI subjects. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26680600 TI - The preventive surgical site infection bundle in patients with colorectal perforation. AB - BACKGROUND: Incisional surgical site infection (SSI) is one of the most frequent complications that occur after colorectal surgery. Surgery for colorectal perforation carries an especially high risk of incisional SSI because fecal ascites contaminates the incision intraoperatively, and in patients who underwent stoma creation, the incision is located near the infective origin and is subject to infection postoperatively. Although effectiveness of the preventive SSI bundle of elective colorectal surgery has been reported, no study has focused exclusively on emergency surgery for colorectal perforation. METHODS: Patients with colorectal perforation who underwent emergency surgery and stoma creation from 2010 to 2015 at our center were consecutively enrolled in the study. In March 2013, we developed the preventive incisional SSI bundle for patients with colorectal perforation undergoing stoma creation. The effectiveness of the bundle in these patients was determined and the rates of incisional SSI between before and after March 2013 were compared. RESULTS: We enrolled 108 patients with colorectal perforation who underwent emergency operation during the study period. Thirteen patients were excluded because they died within 30 days after surgery, and 23 patients without stoma were excluded; thus, 72 patients were analyzed. There were 47 patients in the pre-implementation group and 25 patients in the post-implementation group. The rate of incisional SSI was significantly lower after implementation of preventive incisional SSI bundle (43% vs. 20%, p = 0.049). Postoperative hospital stay was significantly shorter after implementation of the bundle (27 vs. 18 days respectively; p = 0.008). CONCLUSIONS: The preventive incisional SSI bundle was effective in preventing incisional SSI in patients with colorectal perforation undergoing emergency surgery with stoma creation. PMID- 26680602 TI - Maternal smoking during pregnancy and the risk of childhood brain tumors: Results from a Swedish cohort study. AB - BACKGROUND: Tobacco metabolites and carcinogens can be found in placental and umbilical cord tissues of fetuses exposed to maternal smoking. However, studies regarding maternal smoking during pregnancy and childhood brain tumor (CBT) have shown inconsistent results. METHODS: All children born in Sweden between 1983 and 2010 and with information about maternal smoking during pregnancy, obtained from the Swedish Medical Birth Register, were included in this population based cohort study (n=2,577,305). CBT cases were identified from the National Cancer Register. Cox regression models were used to estimate the effect of maternal smoking during pregnancy on the risk of CBTs. RESULTS: We identified 1039 cases of CBT in the cohort. Overall, there was little or no effect of maternal smoking during pregnancy on the risk of CBTs. However, in analyses stratified by age at diagnosis and child's sex, positive associations were found among 5-9 years old children. In this age interval, maternal smoking during pregnancy was associated with an increased risk of all CBTs combined only among male children (RR=1.50, 95% CI 0.96-2.34), while for astrocytoma there was a positive association in both male (RR=2.00, 95% CI 1.02-3.91) and female children (RR=1.80, 95% CI 0.85-3.82). CONCLUSION: Results from this large Swedish cohort study suggest that even though maternal smoking during pregnancy has a limited overall effect on CBTs, it may increase the risk of astrocytomas. PMID- 26680603 TI - Evaluation of breast cancer risk associated with tea consumption by menopausal and estrogen receptor status among Chinese women in Hong Kong. AB - PURPOSE: Experimental studies implicate tea and tea polyphenols may be preventive against breast cancer, but evidence from epidemiological studies has been inconsistent. We conducted a hospital-based case-control study to evaluate the role of tea especially green tea in breast cancer etiology. METHODS: We consecutively recruited 756 incident breast cancer cases and 789 hospital controls who had completed information on tea consumption. We calculated odds ratios (ORs) for tea consumption using unconditional multivariable logistic regression. We further conducted stratified analyses to assess whether the effect of tea consumption varied by menopausal status and estrogen receptor (ER). RESULTS: Overall, 439 (58.1%) breast cancer cases and 434 (55.0%) controls reported habits of regular tea drinking, showing an adjusted OR of 1.01 (95%CI: 0.78-1.31) and 1.20 (95%CI: 0.80-1.78) for any tea and green tea drinking, respectively. Regular tea drinking was significantly associated with a lower risk for breast cancer in pre-menopausal women (OR=0.62, 95%CI: 0.40-0.97) but an increased risk in post-menopausal women (OR=1.40, 95%CI: 1.00-1.96). The positive association among postmenopausal women was strongest among ER-negative green tea drinkers (OR=2.99, 95% CI: 1.26-7.11). CONCLUSIONS: Tea or green tea drinking was not associated with overall breast cancer risk, which may be masked by the differential effect in pre- and post-menopausal women. PMID- 26680604 TI - Polygenic Analysis of Late-Onset Alzheimer's Disease from Mainland China. AB - Recently, a number of single nucleotide polymorphisms (SNPs) were identified to be associated with late-onset Alzheimer disease (LOAD) through genome-wide association study data. Identification of SNP-SNP interaction played an important role in better understanding genetic basis of LOAD. In this study, fifty-eight SNPs were screened in a cohort of 229 LOAD cases and 318 controls from mainland China, and their interaction was evaluated by a series of analysis methods. Seven risk SNPs and six protective SNPs were identified to be associated with LOAD. Risk SNPs included rs9331888 (CLU), rs6691117 (CR1), rs4938933 (MS4A), rs9349407 (CD2AP), rs1160985 (TOMM40), rs4945261 (GAB2) and rs5984894 (PCDH11X); Protective SNPs consisted of rs744373 (BIN1), rs1562990 (MS4A), rs597668 (EXOC3L2), rs9271192 (HLA-DRB5/DRB1), rs157581 and rs11556505 (TOMM40). Among positive SNPs presented above, we found the interaction between rs4938933 (risk) and rs1562990 (protective) in MS4A weakened their each effect for LOAD; for three significant SNPs in TOMM40, their cumulative interaction induced the two protective SNPs effects lost and made the risk SNP effect aggravate for LOAD. Finally, we found rs6656401-rs3865444 (CR1-CD33) pairs were significantly associated with decreasing LOAD risk, while rs28834970-rs6656401 (PTK2B-CR1), and rs28834970 rs6656401 (PTK2B-CD33) were associated with increasing LOAD risk. In a word, our study indicates that SNP-SNP interaction existed in the same gene or cross different genes, which could weaken or aggravate their initial single effects for LOAD. PMID- 26680605 TI - Long-Term Ozone Exposure and Mortality in a Large Prospective Study. AB - RATIONALE: Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive. OBJECTIVES: In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. METHODS: Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant's residence from a hierarchical Bayesian space-time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 MUm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. MEASUREMENTS AND MAIN RESULTS: In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01-1.04), circulatory (HR, 1.03; 95% CI, 1.01-1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08-1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. CONCLUSIONS: Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations. PMID- 26680606 TI - Restoration of t cell substes of patients with type 1 diabetes mellitus by microencapsulated human umbilical cord Wharton jelly-derived mesenchymal stem cells: An in vitro study. AB - Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) might apply to treating chronic autoimmune disorders, as already shown for Sjogren's syndrome, including type 1 diabetes mellitus (T1D). Since naked hUCMS grafts encountered restraints, we enveloped hUCMS, within immunoisolatory microcapsules (CpS-hUCMS), made of our endotoxin-free, clinical grade alginate. We then examined the vitro effects of interferon (IFN)-gamma-pretreated CpS-hUCMS on Th17 and Treg of T1D patients (n=15) and healthy controls (n=10). Peripheral blood mononuclear cells (PBMCs) were co-cultured with PBMC/CpS-hUCMS: lymphocyte proliferation was assessed by carboxyfluorescein succinimidyl esther (CFSE) dilution assay, and phenotypic analysis of regulatory and effector Tc was also performed. Cytokine expression was performed by bead array and qPCR on IFN-gamma pretreated hUCMS before PBMCs co-culture. CpS-hUCMS restored a correct Treg/Th17 ratio, relevant to the T1D disease process. In summary, we have preliminarily developed a new biohybrid system, associated with immunoregulatory properties, that is ready for in vivo application. PMID- 26680607 TI - Hypomorphic function and somatic reversion of DOCK8 cause combined immunodeficiency without hyper-IgE. AB - Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral infections, food allergies and elevated serum IgE. Although patients may present with a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability in patients are poorly defined. Here we characterized a novel compound heterozygous mutation in DOCK8 in a patient diagnosed with primary combined immunodeficiency which was not typical of classical DOCK8 deficiency. In contrast to previously identified mutations in DOCK8 which result in complete loss of function, the newly identified single nucleotide insertion results in expression of a truncated DOCK8 protein. Functional evaluation of the truncated DOCK8 protein revealed its hypomorphic function. In addition we found somatic reversion of DOCK8 predominantly in T cells. The combination of somatic reversion and hypomorphic DOCK8 function explains the milder and atypical phenotype of the patient and further broadens the spectrum of DOCK8-associated disease. PMID- 26680608 TI - Emerging Opportunities for Registered Dietitian Nutritionists to Help Raise a Healthier Generation of Native American Youth. PMID- 26680627 TI - Fixing stem cells via genome editing: hope for cystic fibrosis? PMID- 26680609 TI - The school environment and adolescent physical activity and sedentary behaviour: a mixed-studies systematic review. AB - There is increasing academic and policy interest in interventions aiming to promote young people's health by ensuring that the school environment supports healthy behaviours. The purpose of this review was to summarize the current evidence on school-based policy, physical and social-environmental influences on adolescent physical activity and sedentary behaviour. Electronic databases were searched to identify studies that (1) involved healthy adolescents (11-18 years old), (2) investigated school-environmental influences and (3) reported a physical activity and/or sedentary behaviour outcome or theme. Findings were synthesized using a non-quantitative synthesis and thematic analysis. Ninety three papers of mixed methodological quality were included. A range of school based policy (e.g. break time length), physical (e.g. facilities) and social environmental (e.g. teacher behaviours) factors were associated with adolescent physical activity, with limited research on sedentary behaviour. The mixed studies synthesis revealed the importance of specific activity settings (type and location) and intramural sport opportunities for all students. Important physical education-related factors were a mastery-oriented motivational climate and autonomy supportive teaching behaviours. Qualitative evidence highlighted the influence of the wider school climate and shed light on complexities of the associations observed in the quantitative literature. This review identifies future research needs and discusses potential intervention approaches to be considered. PMID- 26680628 TI - Predicting Pressure Ulcer Development in Clinical Practice: Evaluation of Braden Scale Scores and Nutrition Parameters. AB - PURPOSE: Accurate patient assessment and screening for pressure ulcer (PU) is difficult in the clinical setting, and evaluation of nutritional status is especially problematic. The aim of this retrospective study was to determine the extent to which Braden Scale scores and other nutrition screening parameters (body mass index, poor intake, and weight loss) predict PU development in general and heel and sacral ulcers specifically. METHODS: Records of 230 hospitalized patients who developed PU were compared to a matched control group without PU. Logistic regression was used to determine the association of total Braden scores, Braden nutrition subscale scores, and nutrition factors with PU development at any time, within week 1, or within week 2 of hospitalization; and development of sacral and heel ulcers at these same periods. RESULTS: Braden Scale scores on hospital admission were predictive of hospital-acquired pressure ulcer development at some point during the hospital stay; and more specifically Braden scores on day 7 were predictive of PU development within week 2 of hospitalization. Among nutrition screening factors and PU development, a low body mass index showed a statistically significant relationship with sacral ulcer development. CONCLUSIONS: Findings indicate that the overall Braden score is a valid predictor of PU development. Implications for clinical practice to decrease the risk for PU development include appropriate use of reliable and valid scales by nurses along with careful evaluation of nutrition parameters. PMID- 26680629 TI - The Impact of Radical Cystectomy and Urinary Diversion on Suicidal Death in Patients With Bladder Cancer. AB - PURPOSE: Compared to the general population, suicide is more common in the elderly and in patients with cancer. We sought to examine the incidence of suicide in patients with bladder cancer and evaluate the impact of radical cystectomy in this high-risk population. METHODS: Patients diagnosed with urothelial carcinoma from 1988 to 2010 were identified in the Survey, Epidemiology, and End Results (SEER) database. Contingency tables of suicide rates and standardized mortality ratios (SMRs) and 95% confidence intervals were calculated. Multivariable logistic regression models were performed to generate odds ratios (ORs) for the identification of factors associated with suicide in this population. RESULTS: There were 439 suicides among patients with bladder cancer observed for 1,178,000 person-years (Standard Morbidity Ratio [SMR] = 2.71). All demographic variables analyzed had a higher SMR for suicide compared to the general population, in particular age >=80 years (SMR = 3.12), unmarried status (SMR = 3.41), and white race (SMR = 2.60). The incidence of suicide was higher in the general population for patients who underwent radical cystectomy compared to those who did not (SMR = 3.54 vs SMR = 2.66). On multivariate analysis, the strongest predictors of suicide were male gender (vs female; OR = 6.63) and distant disease (vs localized; OR = 5.43). CONCLUSIONS: Clinicians should be aware of risk factors for suicide in patients diagnosed with bladder cancer, particularly older, white, unmarried patients with distant disease, and/or those who have undergone radical cystectomy. A multidisciplinary team based approach, including wound ostomy care trained nursing staff and mental health care providers, may be essential to provide care required to decrease suicide rates in this at-risk population. PMID- 26680630 TI - Physiological and pathological significance of the molecular cross-talk between autophagy and apoptosis. AB - Autophagy and apoptosis are two important molecular mechanisms that maintain cellular homeostasis under stress conditions. Autophagy represents an intracellular mechanism responsible for turnover of organelles and long-lived proteins through a lysosome-dependent degradation pathway. Cell death signals or sustained stress might trigger programmed cell death pathways, and among them, apoptosis is the most extensively studied one. Recent studies indicate the presence of a complex interplay between autophagy and apoptosis. Physiological relevance of autophagy-apoptosis crosstalk was mainly shown in vitro. However, in vivo consequences possibly exist both during health and disease. In this review, we will summarize the current knowledge about molecular mechanisms connecting autophagy and apoptosis, and about the significance of this crosstalk for human health. PMID- 26680632 TI - Long noncoding RNAs in lung cancer: what we know in 2015. AB - Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. Long noncoding RNAs (lncRNAs), which lacking protein-coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including lung cancer. In this review, we highlight the recent findings of lncRNAs in lung cancer pathogenesis. While our understanding of lncRNAs in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of lncRNAs will certainly secure strong biomarkers and improve treatment options for lung cancer patients. PMID- 26680631 TI - Eight-Shaped Hatching Increases the Risk of Inner Cell Mass Splitting in Extended Mouse Embryo Culture. AB - Increased risk of monozygotic twinning (MZT) has been shown to be associated with assisted reproduction techniques, particularly blastocyst culture. Interestingly, inner cell mass (ICM) splitting in human '8'-shaped hatching blastocysts that resulted in MZT was reported. However, the underlying cause of MZT is not known. In this study, we investigated in a mouse model whether in vitro culture leads to ICM splitting and its association with hatching types. Blastocyst hatching was observed in: (i) in vivo developed blastocysts and (ii-iii) in vitro cultured blastocysts following in vivo or in vitro fertilization. We found that '8'-shaped hatching occurred with significantly higher frequency in the two groups of in vitro cultured blastocysts than in the group of in vivo developed blastocysts (24.4% and 20.4% versus 0.8%, respectively; n = 805, P < 0.01). Moreover, Oct4 immunofluorescence staining was performed to identify the ICM in the hatching and hatched blastocysts. Scattered and split distribution of ICM cells was observed around the small zona opening of '8'-shaped hatching blastocysts. This occurred at a high frequency in the in vitro cultured groups. Furthermore, we found more double OCT4-positive masses, suggestive of increased ICM splitting in '8'-shaped hatching and hatched blastocysts than in 'U'-shaped hatching and hatched blastocysts (12.5% versus 1.9%, respectively; n = 838, P < 0.01). Therefore, our results demonstrate that extended in vitro culture can cause high frequencies of '8'-shaped hatching, and '8'-shaped hatching that may disturb ICM herniation leading to increased risk of ICM splitting in mouse blastocysts. These results may provide insights into the increased risk of human MZT after in vitro fertilization and blastocyst transfer. PMID- 26680634 TI - SEOM Guidelines 2015: a new era in the collaboration with the Spanish Cancer Research Cooperative Groups. PMID- 26680633 TI - Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases. AB - Malignant pleural effusion (MPE) represents 15-35 % of pleural effusions and markedly worsens the prognosis and quality of life of patients with cancer. Malignant mesothelioma (MM) and lung adenocarcinoma are the most frequent primary and secondary causes, respectively, of MPE. Effective treatments for cancer related MPE are warranted in order to improve symptoms, reduce the number of invasive pleural procedures, and prolong patient life. Since angiogenesis plays a key role in MPE development, the potential role of bevacizumab and other anti angiogenic therapies have been explored in this review. No relevant phase III trials have specifically analysed the benefit from adding bevacizumab to platinum based chemotherapy in lung cancer-related MPE. However, small retrospective series reported 71.4-93.3 % MPE control rate, a reduction in invasive procedures, and a safe profile with this combination. Being approved for the first-line treatment of non-squamous advanced NSCLC, the addition of bevacizumab should be considered for patients presenting with MPE. In addition, further studies in this are recommended. In MM, the addition of bevacizumab to platinum-based chemotherapy did not meet primary endpoints in two phase II trials. However, the beneficial results on OS reported in comparison with historical cohorts and the statistically significant benefit on PFS and OS observed in the phase III MAPS trial foretell an eventual role for the combination of platinum/pemetrexed/bevacizumab as front-line systemic therapy for pleural MM. To date, no other anti-angiogenic drug has showed significant benefit in the treatment of patients with either MPE or MM. However, new promising drugs such as ramucirumab or recombinant human endostar warrant further investigation. PMID- 26680635 TI - POEMS syndrome initially presenting with acral dermatitis. PMID- 26680636 TI - Cervical trophoblasts for non-invasive single-cell genotyping and prenatal diagnosis. AB - OBJECTIVE: We aimed at developing a method to recover trophoblastic cells from the cervix through a completely non-invasive approach and obtaining a genetic proof of their fetal nature implying that they can be used for non-invasive prenatal diagnosis (NIPD). METHODS: We studied obstetrical samples from 21 pregnant women between 8 and 12 weeks of gestation scheduled for chorionic villus sampling or undergoing elective termination of pregnancy. A cytobrush was used to extract cells from the external parts of the cervix and transferred to 10 ml of preservative solution. Cells were layered on filters with 8 microns pores using the ISET system (Isolation by SizE of Tumor/Trophoblastic cells) and stained. Putative fetal cells were collected by single cell laser-assisted microdissection and identified as fetal or maternal cells by Short Tandem Repeat genotyping. NIPD was blindly performed on 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy. RESULTS: Trophoblastic cells were recovered from all tested cervical samples with a frequency of 2-12 trophoblasts per 2 ml. NIPD was blindly obtained and verified in 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy. DISCUSSION: Although larger confirmation studies are required, this is the first report providing a solid proof of principle that trophoblasts can be consistently and safely recovered from cervical samples. Since they are a source of pure fetal DNA, i.e. fetal DNA not mixed with maternal DNA, they constitute an ideal target to develop NIPD of recessive diseases, which is a technical challenge for methods based on cell free DNA. PMID- 26680638 TI - Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a meta-analysis. AB - OBJECTIVES: Clonazepam has been used in the treatment of burning mouth syndrome (BMS) for several decades. We conducted a meta-analysis to investigate the efficacy of clonazepam in the treatment of BMS. METHODS: We conducted a search of the PubMed, MEDLINE, EMBASE, Web of Science (TS), and the Cochrane Library databases for relevant studies that met our eligibility criteria (up to September 22, 2015). Statistical analyses were conducted using RevMan 5.2 and STATA 11.0 software. RESULTS: Three randomized controlled trials (RCTs) and two high-quality case-control studies involving 195 BMS patients were selected for this study. Our results show that clonazepam can reduce the oral pain sensation in patients with BMS (WMD: -3.72, 95% CI: -4.57, -2.86; P < 0.05; for all five studies). A positive therapeutic effect was demonstrated for both short-term (<=10 weeks) application (WMD: -1.44, 95% CI: -2.06, -0.82; P < 0.05) and long-term (>10 weeks) application (WMD: -4.50, 95% CI: -4.98, -4.03; P < 0.05). Both topical (WMD: -1.50, 95% CI: -2.14, -0.85; P < 0.05) and systemic (WMD: -3.81, 95% CI: 4.63, -2.98; P < 0.05) administration of clonazepam were confirmed to be effective. CONCLUSION: Clonazepam is effective in inducing symptom remission in patients with BMS. PMID- 26680637 TI - Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. AB - Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low-resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure-driven flow provided by convection-enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus-based or synthetic nonbiodegradable systems. Using a state-of-the-art biodegradable polymer, poly(beta-amino ester), colloidally stable sub-100 nm DNA nanoparticles are engineered with a nonadhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain-penetrating nanoparticles are able to homogeneously distribute throughout the rodent striatum and mediate widespread and high-level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases. PMID- 26680639 TI - Continuity of care in the post partum period: general practitioner experiences with communication. AB - Objectives Informational and management continuity of care assists in providing a seamless transition for women and infants from tertiary or secondary to primary care during the post partum period. Few studies have evaluated the interaction between different aspects of the health system following a woman's discharge from hospital after the birth of her infant. The present study describes how general practitioners (GPs) experience communications with hospitals and other post partum care providers relevant to continuity of care. Methods In the present cross-sectional study, a 52-item questionnaire adapted from a previously used survey was mailed to 932 GPs in southern Queensland, Australia, between February and July 2013. Questionnaire items included participant demographics, the timeliness and usability of discharge summaries, communication with other post partum care providers and consultation practices. Results The response rate was 17.4%. Nearly one-quarter of participants never or rarely received a hospital discharge summary in a timely manner and most considered the summaries somewhat useful. Few GPs (14.3%) had contact with or received information from domiciliary midwives who conducted post partum home visits. A higher proportion (38%) had some communication with a Child and Family Health nurse in the month before the survey. Conclusions Information flow from hospital to general practice and between other post partum care providers is less than ideal and may affect ongoing care for mothers and infants, especially those at risk. Knowledge exchange between healthcare services and initiatives to improve information sharing needs to be developed and implemented. What is already known on this topic? Transitions from tertiary or secondary care to primary care and between primary care providers are often times of vulnerability for patients, including women and infants in the post partum period. There is little information documenting communications between different maternity services and GPs that facilitate ongoing care. What does this paper add? There are significant gaps in the exchange of information about post partum women and infants from hospitals to GPs and a lack of communication between GPs and other post partum care providers, such as domiciliary midwives and Child and Family Health nurses. What are the implications for practitioners? Improvements in the timeliness, presentation and content of hospital discharge summaries, as well as enhancing channels of communication, collaboration, cooperation and information sharing between providers of community post partum care, are necessary if mothers are to receive the best care possible. PMID- 26680640 TI - Response on: Comments on "Salivary 8-hydroxy-2-deoxyguanosine, malondialdehyde, vitamin C, and vitamin E in oral pre-cancer and cancer: diagnostic value and free radical mechanism of action". PMID- 26680641 TI - High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers. AB - BACKGROUND: Triple negative breast cancers (TNBC) are a more aggressive subset of breast cancer. A better understanding of its biology could allow the rational development of targeted therapies. METHODS: We extensively analyzed the EGFR/PI3K/PTEN axis in a large, homogeneous population of TNBC to help defining the putative role of anti-EGFR and -PI3K targeted therapies in this setting. EGFR gene amplification, EGFR protein expression, PIK3CA and PTEN gene alterations (two members of EGFR downstream pathways) and their clinicopathological and prognostic implications were analyzed in 204 TNBC samples from European patients. RESULTS: EGFR amplification was detected in 18 of the 204 TNBC specimens (8.9 %) and was significantly associated with higher EGFR protein levels. Fourteen PIK3CA mutations were identified in exon 9 (6.7 %), and 17 in exon 20 (8.3 %). PIK3CA mutations, especially in exon 9, were significantly associated with grade I-II tumors. PTEN deletions were detected in 43 samples (21.50 %) and were significantly associated with grade III tumors (p < 0.001). Univariate analysis showed a significant association between relapse-free survival (RFS), T and N stage and exon 9 PIK3CA mutations. Overall survival was significantly associated with T stage, N stage and adjuvant chemotherapy, which was administered to 70.3 % of patients. In multivariate analyses, T stage, N stage, presence of exon 9 PIK3CA mutations and high EGFR protein level were independent poor prognostic factors for RFS, while adjuvant chemotherapy was associated with a better outcome. CONCLUSIONS: High EGFR protein expression and exon 9 PIK3CA activating mutations are independent prognostic factors in TNBC. The efficacy of anti-PI3K targeted therapies needs to be evaluated in this setting. PMID- 26680642 TI - The Moderating Role of Gender in the Relationship Between Tobacco Outlet Exposure and Tobacco Use Among African American Young Adults. AB - Tobacco outlet exposure is a correlate of tobacco use with potential differences by gender that warrant attention. The aim of this study is to explore the moderating role of gender in the relationship between tobacco outlet exposure and past month tobacco use among African American young adults 21 to 24 years old. This cross-sectional study (n = 283) used geospatial methods to determine the number of tobacco outlets within walking distance (i.e., a quarter mile) of participants' homes and distance to the nearest outlet. Logistic regression models were used to test interactions between gender and tobacco outlet exposure (i.e., density and proximity). Tobacco outlets were classified based on whether or not they were licensed to sell tobacco only (TO outlets) or tobacco and alcohol (TA outlets). Neither density nor proximity was associated with past month tobacco use in the pooled models. However, gender modified the relationship between TO outlet density and tobacco use, and this relationship was significant only among women (OR = 1.02; p < 0.01; adjusted OR = 1.01; p < 0.05). This study underscores the importance of reducing tobacco outlet density in residential neighborhoods, especially TO outlets, as well as highlights potential gender differences in the relationship between tobacco outlet density and tobacco use. PMID- 26680643 TI - Changes in hormone flux and signaling in white spruce (Picea glauca) seeds during the transition from dormancy to germination in response to temperature cues. AB - BACKGROUND: Seeds use environmental cues such as temperature to coordinate the timing of their germination, allowing plants to synchronize their life history with the seasons. Winter chilling is of central importance to alleviate seed dormancy, but very little is known of how chilling responses are regulated in conifer seeds. White spruce (Picea glauca) is an important conifer species of boreal forests in the North American taiga. The recent sequencing and assembly of the white spruce genome allows for comparative gene expression studies toward elucidating the molecular mechanisms governing dormancy alleviation by moist chilling. Here we focused on hormone metabolite profiling and analyses of genes encoding components of hormone signal transduction pathways, to elucidate changes during dormancy alleviation and to help address how germination cues such as temperature and light trigger radicle emergence. RESULTS: ABA, GA, and auxin underwent considerable changes as seeds underwent moist chilling and during subsequent germination; likewise, transcripts encoding hormone-signaling components (e.g. ABI3, ARF4 and Aux/IAA) were differentially regulated during these critical stages. During moist chilling, active IAA was maintained at constant levels, but IAA conjugates (IAA-Asp and IAA-Glu) were substantially accumulated. ABA concentrations decreased during germination of previously moist chilled seeds, while the precursor of bioactive GA1 (GA53) accumulated. We contend that seed dormancy and germination may be partly mediated through the changing hormone concentrations and a modulation of interactions between central auxin-signaling pathway components (TIR1/AFB, Aux/IAA and ARF4). In response to germination cues, namely exposure to light and to increased temperature: the transfer of seeds from moist-chilling to 30 degrees C, significant changes in gene transcripts and protein expression occurred during the first six hours, substantiating a very swift reaction to germination-promoting conditions after seeds had received sufficient exposure to the chilling stimulus. CONCLUSIONS: The dormancy to germination transition in white spruce seeds was correlated with changes in auxin conjugation, auxin signaling components, and potential interactions between auxin-ABA signaling cascades (e.g. the transcription factor ARF4 and ABI3). Auxin flux adds a new dimension to the ABA:GA balance mechanism that underlies both dormancy alleviation by chilling, and subsequent radicle emergence to complete germination by warm temperature and light stimuli. PMID- 26680644 TI - The occurrence of spermatozoa in the ovary of the gynogenetic viviparous teleost Poecilia formosa (POECILIIDAE). AB - The reproductive mode of the female viviparous teleost Poecilia formosa (Poeciliidae) represents the phenomenon known as gynogenesis; that is, parthenogenetic development is initiated by spermatozoa which are needed for physiological activation of the egg and the initiation of gestation, but spermatozoa are prevented from contributing to the genome of the embryo. For the reason that no previous histological analyses of the ovary of this species during the reproductive cycle has been published the present study has been conducted. This study examined the histology of the ovary of P. formosa during nongestation and gestation phases and identified the presence of spermatozoa inside the ovary. Spermatozoa were observed in folds of the ovarian epithelium of P. formosa during both the nongestation and gestation phases. Sperm storage as documented in this study is a very important trait for the gynogenetic viviparous fish P. formosa contributing to the understanding of this species reproduction. PMID- 26680645 TI - Comparison between the triglycerides standardization of routine methods used in Japan and the chromotropic acid reference measurement procedure used by the CDC Lipid Standardization Programme. AB - Background The US Centers for Disease Control and Prevention ensured adequate performance of the routine triglycerides methods used in Japan by a chromotropic acid reference measurement procedure used by the Centers for Disease Control and Prevention lipid standardization programme as a reference point. We examined standardized data to clarify the performance of routine triglycerides methods. Methods The two routine triglycerides methods were the fluorometric method of Kessler and Lederer and the enzymatic method. The methods were standardized using 495 Centers for Disease Control and Prevention reference pools with 98 different concentrations ranging between 0.37 and 5.15 mmol/L in 141 survey runs. The triglycerides criteria for laboratories which perform triglycerides analyses are used: accuracy, as bias <=5% from the Centers for Disease Control and Prevention reference value and precision, as measured by CV, <=5%. Results The correlation of the bias of both methods to the Centers for Disease Control and Prevention reference method was: y (%bias) = 0.516 * (Centers for Disease Control and Prevention reference value) -1.292 ( n = 495, R2 = 0.018). Triglycerides bias at medical decision points of 1.13, 1.69 and 2.26 mmol/L was -0.71%, -0.42% and 0.13%, respectively. For the combined precision, the equation y (CV) = -0.398 * (triglycerides value) + 1.797 ( n = 495, R2 = 0.081) was used. Precision was 1.35%, 1.12% and 0.90%, respectively. It was shown that triglycerides measurements at Osaka were stable for 36 years. Conclusions The epidemiologic laboratory in Japan met acceptable accuracy goals for 88.7% of all samples, and met acceptable precision goals for 97.8% of all samples measured through the Centers for Disease Control and Prevention lipid standardization programme and demonstrated stable results for an extended period of time. PMID- 26680646 TI - Screening for antibodies against Treponema pallidum with chemiluminescent microparticle immunoassay: analysis of discordant serology results and clinical characterization. AB - BACKGROUND: Traditionally, testing for syphilis has consisted of initial screening with a non-treponemal test, then retesting reactive specimens with a treponemal test. Recent availability of a chemiluminescent microparticle immunoassay for detecting antibodies against Treponema pallidum has led several laboratories in China to adopt chemiluminescent microparticle immunoassay for screening of syphilis, with subsequent testing of reactive serum samples with non treponemal tests. We evaluated the utility of chemiluminescent microparticle immunoassay for routine screening of syphilis. METHODS: Antibodies against Treponema pallidum were screened in 20,550 serum samples using chemiluminescent microparticle immunoassay. Chemiluminescent microparticle immunoassay-positive samples were reflexively tested with rapid plasma reagin tests and Treponema pallidum particle agglutination assays. Dot-immunoblot assays were used to confirm results of chemiluminescent microparticle immunoassay-positive and Treponema pallidum particle agglutination-negative serum samples. RESULTS: Overall, 267 samples (1.3%) were chemiluminescent microparticle immunoassay positive, and 185 (69.3%) of those chemiluminescent microparticle immunoassay positive serum samples were also Treponema pallidum particle agglutination positive. Samples' signal to cut-off ratio for chemiluminescent microparticle immunoassay correlated with diagnostic reliability, as greater samples' signal to cut-off ratio corresponded with greater concordance between chemiluminescent microparticle immunoassay and Treponema pallidum particle agglutination results. Dot-immunoblot testing of 82 chemiluminescent microparticle immunoassay-positive and Treponema pallidum particle agglutination-negative serum samples showed that 16 samples (19.5%) were Dot-immunoblot-positive, 28 (34.2%) were indeterminate and 38 (46.3%) were negative. CONCLUSIONS: Because there is a certain percentage of false-positive results using chemiluminescent microparticle immunoassay for routine screening of syphilis, further analysis by Treponema pallidum particle agglutination is recommended to confirm diagnostic results. While in screening populations discrepancies between chemiluminescent microparticle immunoassay and Treponema pallidum particle agglutination results are quite prevalent, confirmation by immunoblot assay may be useful. PMID- 26680648 TI - Sacroiliac Joint Magnetic Resonance Imaging in the Diagnosis of Axial Spondyloarthritis: "A Tiny Bit of White on Two Consecutive Slices" May Be Objective, but Not Specific. PMID- 26680649 TI - New concept: cellular senescence in pathophysiology of cholangiocarcinoma. AB - Cholangiocarcinoma, a malignant tumor arising in the hepatobiliary system, presents with poor prognosis because of difficulty in its early detection/diagnosis. Recent progress revealed that cellular senescence may be involved in the pathophysiology of cholangiocarcinoma. Cellular senescence is defined as permanent growth arrest caused by several cellular injuries, such as oncogenic mutations and oxidative stress. "Oncogene-induced" and/or stress induced senescence may occur in the process of multi-step cholangiocarcinogenesis, and overexpression of a polycomb group protein EZH2 may play a role in the escape from, and/or bypassing of, senescence. Furthermore, senescent cells may play important roles in tumor development and progression via the production of senescence-associated secretory phenotypes. Cellular senescence may be a new target for the prevention, early diagnosis, and therapy of cholangiocarcinoma in the near future. PMID- 26680650 TI - Array-based molecular karyotyping in fetal brain malformations: Identification of novel candidate genes and chromosomal regions. AB - BACKGROUND: For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS: Here, we used array-based molecular karyotyping to search for causative CNVs in 33 fetuses of terminated pregnancies with prenatally detected brain malformations and additional extracerebral anomalies. RESULTS: In 11 fetuses, we identified 15 CNVs (0.08 Mb to 29.59 Mb), comprising four duplications and eleven deletions. All larger CNVs (> 5 Mb) had also been detected by prenatal conventional karyotyping. None of these CNVs was present in our 1307 healthy in-house controls (frequency < 0.0008). Among these CNVs, we prioritized six chromosomal regions (1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, 18q21.1) due to their previous association with human brain malformations or owing to the presence of a single gene expressed in human brain. Prioritized genes within these regions were UBTD2, SKA1, SVIP, and, most convincingly, GPR52. However, re-sequencing of GPR52 in 100 samples from fetuses with brain malformations or patients with intellectual disability and brain malformations revealed no disease-causing mutation. CONCLUSION: Our study suggests chromosomal regions 1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, and 18q21.1 to be involved in human brain development. Within three of these regions, we suggest UBTD2, GPR52, and SKA1 as possible candidate genes. Because the overall detection rate of array-based molecular karyotyping was slightly higher (23%) than that of conventional prenatal karyotyping (20%), we suggest it's use for prenatal diagnostic testing in fetuses with nonisolated brain malformations. PMID- 26680651 TI - Retaining individualities: the photodynamics of self-ordering porphyrin assemblies. AB - The retention of photochemical properties of individual chromophores is a key feature of biological light harvesting complexes. This is achieved despite extensive aggregation of the chromophores, which in synthetic chromophore assemblies often yields a change in spectral characteristics. As an alternative approach towards mimicking biological light harvesting complexes, we report the synthesis of porphyrin assemblies which retained the photochemical properties of the individual chromophore units despite their substantial aggregation. These new materials highlight a new bottom-up approach towards the design and understanding of more complex biomimetic and naturally occurring biological systems. PMID- 26680653 TI - Hidden Markov induced Dynamic Bayesian Network for recovering time evolving gene regulatory networks. AB - Dynamic Bayesian Networks (DBN) have been widely used to recover gene regulatory relationships from time-series data in computational systems biology. Its standard assumption is 'stationarity', and therefore, several research efforts have been recently proposed to relax this restriction. However, those methods suffer from three challenges: long running time, low accuracy and reliance on parameter settings. To address these problems, we propose a novel non-stationary DBN model by extending each hidden node of Hidden Markov Model into a DBN (called HMDBN), which properly handles the underlying time-evolving networks. Correspondingly, an improved structural EM algorithm is proposed to learn the HMDBN. It dramatically reduces searching space, thereby substantially improving computational efficiency. Additionally, we derived a novel generalized Bayesian Information Criterion under the non-stationary assumption (called BWBIC), which can help significantly improve the reconstruction accuracy and largely reduce over-fitting. Moreover, the re-estimation formulas for all parameters of our model are derived, enabling us to avoid reliance on parameter settings. Compared to the state-of-the-art methods, the experimental evaluation of our proposed method on both synthetic and real biological data demonstrates more stably high prediction accuracy and significantly improved computation efficiency, even with no prior knowledge and parameter settings. PMID- 26680652 TI - Body composition of patients with Duchenne muscular dystrophy: the Greek experience. AB - : Greece ranks among the first countries suffering from the obesity epidemic globally. The aim of the study was to evaluate body composition in Greek patients with Duchenne muscular dystrophy (DMD). We hypothesized that able-bodied patients would not differ from controls, in terms of adiposity, based on clinical observations during everyday practice. STUDY DESIGN: Cross-sectional study of steroid-dependent DMD subjects, who underwent dual-energy X-ray absorptiometry and laboratory metabolic bone profile evaluation. Forty-two patients and thirty one controls were studied. Overall, DMD subjects were shorter (height Z-score = 1.4, p = 0.01). Their bone mineral density (BMD) was low (lumbar spine BMD Z score = -1.2, p < 0.01, subcranial total body BMD Z-score = -1.8, p < 0.01). Lean tissue mass (LTM) was also decreased (LTM Z-score = -2.2, p < 0.01). The above findings were more pronounced in adolescence. Regarding adiposity, increased fat mass (FM) was found only in pubertal DMD patients (FM Z-score = 1.4, p < 0.01), whereas prepubertal, able-bodied patients did not differ from controls, thus confirming the initial hypothesis. Finally, 65 % of DMD subjects had increased bone resorption markers and 57 % had suboptimal vitamin D levels. The importance of using native population as controls for body composition analysis is highlighted. In Greece, abnormal body composition in DMD patients is more striking when loss of ambulation occurs and not during the prepubertal period, due to the concurrent presence of obesity in the pediatric population. Thus, adolescents with this neuromuscular disorder should be targeted toward prompt lifestyle interventions. PMID- 26680654 TI - Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers. AB - The purpose of the present study was to investigate the effect of resveratrol (RSV) pretreatment on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy human volunteers. The open-label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CHZ dosing at predetermined time intervals and analyzed by HPLC. RSV pretreatment significantly enhanced the maximum plasma concentration (Cmax), area under the curve (AUC) and half life (T1/2) and significantly decreased elimination rate constant (Kel), apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F) of CHZ as compared to that of control. In addition, RSV pretreatment significantly decreased the metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC and T1/2 and significantly increased the Kel ratio of 6 OHCHZ/CHZ, which indicated the reduced formation of CHZ to 6-OHCHZ. The results suggest that the altered CYP2E1 enzyme activity and pharmacokinetics of CHZ might be attributed to RSV mediated inhibition of CYP2E1 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CHZ. The inhibition of CYP2E1 by RSV may provide a novel approach for minimizing the hepatotoxicity of ethanol. PMID- 26680655 TI - Mode-evolution-based polarization rotation and coupling between silicon and hybrid plasmonic waveguides. AB - Hybrid plasmonic (HP) modes allow strong optical field confinement and simultaneously low propagation loss, offering a potentially compact and efficient platform for on-chip photonic applications. However, their implementation is hampered by the low coupling efficiency between dielectric guided modes and HP modes, caused by mode mismatch and polarization difference. In this work, we present a mode-evolution-based polarization rotation and coupling structure that adiabatically rotates the TE mode in a silicon waveguide and couples it to the HP mode in a strip silicon-dielectric-metal waveguide. Simulation shows that high coupling factors of 92%, 78%, 75%, and 73% are achievable using Ag, Au, Al, and Cu as the metal cap, respectively, at a conversion length of about 5 MUm. For an extremely broad wavelength range of 1300-1800 nm, the coupling factor is >64% with a Ag metal cap, and the total back-reflection power, including all the mode reflections and backscattering, is below -40 dB, due to the adiabatic mode transition. Our device does not require high-resolution lithography and is tolerant to fabrication variations and imperfections. These attributes together make our device suitable for optical transport systems spanning all telecommunication bands. PMID- 26680656 TI - Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial neoplasms. AB - OBJECTIVE: As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma. METHODS/MATERIALS: Pten(loxP/loxP) mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed. RESULTS: Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment. CONCLUSIONS: Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms. PMID- 26680657 TI - An Allelic Series of bak1 Mutations Differentially Alter bir1 Cell Death, Immune Response, Growth, and Root Development Phenotypes in Arabidopsis thaliana. AB - Receptor-like kinases (RLKs) mediate cell-signaling pathways in Arabidopsis thaliana, including those controlling growth and development, immune response, and cell death. The RLK coreceptor BRI1-ASSOCIATED KINASE-1 (BAK1) partners with multiple ligand-binding RLKs and contributes to their signaling in diverse pathways. An additional RLK, BAK1-INTERACTING RECEPTOR-1 (BIR1), physically interacts with BAK1, and loss-of-function mutations in BIR1 display constitutive activation of cell death and immune response pathways and dwarfism and a reduction in lateral root number. Here we show that bir1 plants display defects in primary root growth, characterize bir1 lateral root defects, and analyze expression of BIR1 and BAK1 promoters within the root. Using an allelic series of bak1 mutations, we show that loss of BAK1 function in immune response pathways can partially suppress bir1 cell death, immune response, and lateral root phenotypes and that null bak1 alleles enhance bir1 primary root phenotypes. Based on our data, we propose a model in which BIR1 functions to regulate BAK1 participation in multiple pathways. PMID- 26680658 TI - A Delicate Balance Between Repair and Replication Factors Regulates Recombination Between Divergent DNA Sequences in Saccharomyces cerevisiae. AB - Single-strand annealing (SSA) is an important homologous recombination mechanism that repairs DNA double strand breaks (DSBs) occurring between closely spaced repeat sequences. During SSA, the DSB is acted upon by exonucleases to reveal complementary sequences that anneal and are then repaired through tail clipping, DNA synthesis, and ligation steps. In baker's yeast, the Msh DNA mismatch recognition complex and the Sgs1 helicase act to suppress SSA between divergent sequences by binding to mismatches present in heteroduplex DNA intermediates and triggering a DNA unwinding mechanism known as heteroduplex rejection. Using baker's yeast as a model, we have identified new factors and regulatory steps in heteroduplex rejection during SSA. First we showed that Top3-Rmi1, a topoisomerase complex that interacts with Sgs1, is required for heteroduplex rejection. Second, we found that the replication processivity clamp proliferating cell nuclear antigen (PCNA) is dispensable for heteroduplex rejection, but is important for repairing mismatches formed during SSA. Third, we showed that modest overexpression of Msh6 results in a significant increase in heteroduplex rejection; this increase is due to a compromise in Msh2-Msh3 function required for the clipping of 3' tails. Thus 3' tail clipping during SSA is a critical regulatory step in the repair vs. rejection decision; rejection is favored before the 3' tails are clipped. Unexpectedly, Msh6 overexpression, through interactions with PCNA, disrupted heteroduplex rejection between divergent sequences in another recombination substrate. These observations illustrate the delicate balance that exists between repair and replication factors to optimize genome stability. PMID- 26680659 TI - Targeting of P-Element Reporters to Heterochromatic Domains by Transposable Element 1360 in Drosophila melanogaster. AB - Heterochromatin is a common DNA packaging form employed by eukaryotes to constitutively silence transposable elements. Determining which sequences to package as heterochromatin is vital for an organism. Here, we use Drosophila melanogaster to study heterochromatin formation, exploiting position-effect variegation, a process whereby a transgene is silenced stochastically if inserted in proximity to heterochromatin, leading to a variegating phenotype. Previous studies identified the transposable element 1360 as a target for heterochromatin formation. We use transgene reporters with either one or four copies of 1360 to determine if increasing local repeat density can alter the fraction of the genome supporting heterochromatin formation. We find that including 1360 in the reporter increases the frequency with which variegating phenotypes are observed. This increase is due to a greater recovery of insertions at the telomere-associated sequences (~50% of variegating inserts). In contrast to variegating insertions elsewhere, the phenotype of telomere-associated sequence insertions is largely independent of the presence of 1360 in the reporter. We find that variegating and fully expressed transgenes are located in different types of chromatin and that variegating reporters in the telomere-associated sequences differ from those in pericentric heterochromatin. Indeed, chromatin marks at the transgene insertion site can be used to predict the eye phenotype. Our analysis reveals that increasing the local repeat density (via the transgene reporter) does not enlarge the fraction of the genome supporting heterochromatin formation. Rather, additional copies of 1360 appear to target the reporter to the telomere associated sequences with greater efficiency, thus leading to an increased recovery of variegating insertions. PMID- 26680660 TI - Genetic Variant Selection: Learning Across Traits and Sites. AB - We consider resequencing studies of associated loci and the problem of prioritizing sequence variants for functional follow-up. Working within the multivariate linear regression framework helps us to account for the joint effects of multiple genes; and adopting a Bayesian approach leads to posterior probabilities that coherently incorporate all information about the variants' function. We describe two novel prior distributions that facilitate learning the role of each variable site by borrowing evidence across phenotypes and across mutations in the same gene. We illustrate their potential advantages with simulations and reanalyzing a data set of sequencing variants. PMID- 26680661 TI - Cas9 Variants Expand the Target Repertoire in Caenorhabditis elegans. AB - The proliferation of CRISPR/Cas9-based methods in Caenorhabditis elegans has enabled efficient genome editing and precise genomic tethering of Cas9 fusion proteins. Experimental designs using CRISPR/Cas9 are currently limited by the need for a protospacer adjacent motif (PAM) in the target with the sequence NGG. Here we report the characterization of two modified Cas9 proteins in C. elegans that recognize NGA and NGCG PAMs. We found that each variant could stimulate homologous recombination with a donor template at multiple loci and that PAM specificity was comparable to that of wild-type Cas9. To directly compare effectiveness, we used CRISPR/Cas9 genome editing to generate a set of assay strains with a common single-guide RNA (sgRNA) target sequence, but that differ in the juxtaposed PAM (NGG, NGA, or NGCG). In this controlled setting, we determined that the NGA PAM Cas9 variant can be as effective as wild-type Cas9. We similarly edited a genomic target to study the influence of the base following the NGA PAM. Using four strains with four NGAN PAMs differing only at the fourth position and adjacent to the same sgRNA target, we observed that efficient homologous replacement was attainable with any base in the fourth position, with an NGAG PAM being the most effective. In addition to demonstrating the utility of two Cas9 mutants in C. elegans and providing reagents that permit CRISPR/Cas9 experiments with fewer restrictions on potential targets, we established a means to benchmark the efficiency of different Cas9::PAM combinations that avoids variations owing to differences in the sgRNA sequence. PMID- 26680662 TI - Signatures of Dobzhansky-Muller Incompatibilities in the Genomes of Recombinant Inbred Lines. AB - In the construction of recombinant inbred lines (RILs) from two divergent inbred parents certain genotype (or epigenotype) combinations may be functionally "incompatible" when brought together in the genomes of the progeny, thus resulting in sterility or lower fertility. Natural selection against these epistatic combinations during inbreeding can change haplotype frequencies and distort linkage disequilibrium (LD) relations between loci on the same or on different chromosomes. These LD distortions have received increased experimental attention, because they point to genomic regions that may drive a Dobzhansky Muller type of reproductive isolation and, ultimately, speciation in the wild. Here we study the selection signatures of two-locus epistatic incompatibility models and quantify their impact on the genetic composition of the genomes of two way RILs obtained by selfing. We also consider the biases introduced by breeders when trying to counteract the loss of lines by selectively propagating only viable seeds. Building on our theoretical results, we develop model-based maximum likelihood (ML) tests that can be applied to multilocus RIL genotype data to infer the precise mode of incompatibility as well as the relative fitness of incompatible loci. We illustrate this ML approach in the context of two published Arabidopsis thaliana RIL panels. Our work lays the theoretical foundation for studying more complex systems such as RILs obtained by sibling mating and/or from multiparental crosses. PMID- 26680663 TI - The crystal structure of Z-(Aib)10-OH at 0.65 A resolution: three complete turns of 310-helix. AB - The synthetic peptide Z-(Aib)10-OH was crystallized from hot methanol by slow evaporation. The crystal used for data collection reflected synchrotron radiation to sub-atomic resolution, where the bonding electron density becomes visible between the non-hydrogen atoms. Crystals belong to the centrosymmetric space group P1. Both molecules in the asymmetric unit form regular 310 -helices. All residues in each molecule possess the same handedness, which is in contrast to all other crystal structure determined to date of longer Aib-homopeptides. These other peptides are C-terminal protected by OtBu or OMe. In these cases, because of the missing ability of the C-terminal protection group to form a hydrogen bond to the residue i-3, the sense of the helix is reversed in the last residue. Here, the C-terminal OH-groups form hydrogen bonds to the residues i-3, in part mediated by water molecules. This makes Z-(Aib)10-OH an Aib-homopeptide with three complete 310-helical turns in spite of the shorter length it has compared with Z-(Aib)11-OtBu, the only homopeptide to date with three complete turns. PMID- 26680665 TI - Fasting and nonfasting triglycerides in cardiovascular and other diseases. AB - Moderately elevated plasma/serum triglycerides (2-10 mmol/l) signalize increased risk for cardiovascular disease or presence of non-alcoholic steatohepatitis. Extremely elevated triglycerides (more than 10 mmol/l) signalize increased risk for pancreatitis and lipemia retinalis. The concentration of triglycerides is regulated by many genetic and nongenetic factors. Extremely elevated triglycerides not provoked by nutritional factors, especially inappropriate alcohol intake are more likely to have a monogenic cause. On the contrary, mildly to moderately elevated triglycerides are often caused by polygenic disorders; these could be also associated with central obesity, insulin resistance, and diabetes mellitus. Concentration of triglycerides is also closely interconnected with presence of atherogenic remnant lipoproteins, impaired reverse cholesterol transport and more atherogenic small LDL particles. In general, there is tight association between triglycerides and many other metabolic factors including intermediate products of lipoprotein metabolism which are frequently atherogenic. Therefore, reliable evaluation of the independent role of triglycerides especially in atherosclerosis and cardiovascular disease is difficult. In individual cases values of HDL cholesterol, non-HDL cholesterol (total minus HDL cholesterol), non-HDL/nonLDL cholesterol (total minus HDL minus LDL cholesterol, especially in nonfasting status), atherogenic index of plasma and/or apolipoprotein B could help in decisions regarding aggressiveness of treatment. PMID- 26680666 TI - Treatment of hypertriglyceridemia: a review of current options. AB - Hypertriglyceridemia is an important marker of increased levels of highly atherogenic remnant-like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in combination with statins. Niacin and omega-3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti-sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega-3 fatty acids or niacin). PMID- 26680667 TI - Genetic predisposition of human plasma triglyceride concentrations. AB - The issue of plasma triglyceride levels relative to the risk of development of cardiovascular disease, as well as overall mortality, has been actively discussed for many years. Like other cardiovascular disease risk factors, final plasma TG values have environmental influences (primarily dietary habits, physical activity, and smoking), and a genetic predisposition. Rare mutations (mainly in the lipoprotein lipase and apolipoprotein C2) along with common polymorphisms (within apolipoprotein A5, glucokinase regulatory protein, apolipoprotein B, apolipo-protein E, cAMP responsive element binding protein 3-like 3, glycosylphosphatidylinositol-anchored HDL-binding protein 1) play an important role in determining plasma TG levels. PMID- 26680668 TI - Association between fasting plasma triglycerides, all-cause and cardiovascular mortality in Czech population. Results from the HAPIEE study. AB - Dyslipidemia is the risk factor of cardiovascular disease, but the relationship between the plasma triglyceride (TG) levels and total/cardiovascular mortality has not yet been analyzed in Slavs. The aim of our study was to analyze the association between the fasting TG levels and all-cause/cardiovascular mortality. We have examined 3,143 males and 3,650 females, aged 58.3+/-7.1 years. 729 deaths (274 cardiovascular deaths) have been registered during up to 11.8 years of follow-up. Age-sex adjusted all-cause mortality was higher in individuals with TG values 3.01-4.00 mmol/l (HR 1.37, 95 % CI 1.02-1.83, P=0.035) and over 4.00 mmol/l (HR 1.66, 95 % CI 1.21-2.27, P=0.002) when compared with a reference group (TG 1.41-1.80 mmol/l). Elevated risk remains significant when adjusted for education, marital status and unemployment. When further adjusted for smoking, BMI and dyslipidemia interventions, HR for those in above 4.00 mmol/l group decreased (1.42, P=0.04). The results have been similar when cardiovascular mortality has been examined, however, results reached statistical significance only for the TG over 4.0 mmol/l (P=0.028). Our results confirmed that enhanced plasma levels of plasma triglycerides are dose dependently associated with increased risk of all-cause mortality, however, it seems that individuals with TG values 1.8-3.0 mmol/l are not in higher risk of death. PMID- 26680669 TI - The effect of glucose when added to a fat load on the response of glucagon-like peptide-1 (GLP-1) and apolipoprotein B-48 in the postprandial phase. AB - Increased and prolonged postprandial lipemia has been identified as a risk factor of cardiovascular disease. However, there is no consensus on how to test postprandial lipemia, especially with respect to the composition of an experimental meal. To address this question of how glucose, when added to a fat load, affects the selected parameters of postprandial lipemia, we carried out a study in 30 healthy male volunteers. Men consumed an experimental meal containing either 75 g of fat + 25 g of glucose (F+G meal) or 75 g of fat (F meal) in a control experiment. Blood was taken before the meal and at selected time points within the following 8 h. Glucose, when added to a fat load, induced an increase of glycemia and insulinemia and, surprisingly, a 20 % reduction in the response of both total and active glucagon-like peptide-1 (GLP-1) concentration. The addition of glucose did not affect the magnitude of postprandial triglyceridemia and TRL-C and TRL-TG concentrations but stimulated a faster response of chylomicrons to the test meal, evaluated by changes in apolipoprotein B-48 concentrations. The addition of glucose induced the physiological response of insulin and the lower response of GLP-1 to the test meal during the early postprandial phase, but had no effect on changes of TRL-cholesterol and TRL-TG within 8 h after the meal. PMID- 26680670 TI - Moderate alcohol consumption and triglyceridemia. AB - The review aims to summarize current knowledge on the effects of moderate alcohol consumption (1 standard drink a day for women; 2 drinks a day for men) on triglyceride concentration in circulation. Current evidence suggests that the relationship between alcohol consumption and triglyceridemia is J-shaped. Triglyceridemia is lowest in subjects who drink 10-20 g/alcohol a day. Such a J shaped association is comparable with that described for the relationship between alcohol and cardiovascular risk. On the contrary, alcohol taken with a meal increases and prolongs postprandial triglyceridemia. Such effects of alcohol consumption may be at least partially explained by the effects of ethanol on lipoprotein lipase (LPL) activity. Long-term moderate alcohol consumption increases LPL activity, which may explain its TG-lowering effect. On the other hand, LPL activity is acutely downregulated by ethanol, which explains increased postprandial triglyceridemia. PMID- 26680671 TI - Association of intima-media thickness of carotid arteries with remnant lipoproteins in men and women. AB - The subclass of triglyceride-rich lipoproteins - remnant-like particles (RLP) seems to be strong and independent risk factor for cardiovascular disease. We evaluated the role of RLP and other risk factors (RF) with sonographically measured intima-media thickness of carotid arteries (IMT CCA) in a cohort of Czech population including women defined according to the time after menopause. We investigated relation of IMT CCA to age, weight, central obesity, plasma lipids including remnant-like particles cholesterol (RLP-C) and triglycerides (RLP-TG) in 136 men and 160 women. Using multiple linear regression analysis, significant association between IMT CCA and RLP-C was found in women 1-7 years after menopause. In the whole group of women, only age and fasting blood glucose were independently associated with IMT CCA. In men only age significantly correlated with IMT CCA. Significant decrease of all plasma lipids between 1988 and 1996 in men was detected, while in women significant increase in triglycerides and no change in non-HDL cholesterol was observed. RLP-C was the strongest independent RF for atherosclerosis in postmenopausal women but its association with IMT CCA was limited to several years after menopause. In conclusion, women changing reproductive status could be more sensitive to atherogenic impact of remnant lipoproteins. PMID- 26680672 TI - Hypertriglyceridemic waist - a simple clinical tool to detect cardiometabolic risk: comparison with harmonized definition of metabolic syndrome. AB - With the increasing prevalence of obesity and especially abdominal obesity, a simple clinical tool is needed that identifies the cardiometabolic risk for cardiovascular disease and type 2 diabetes. The aim of our study was to evaluate a broad spectrum of metabolic variables and IMT in subjects with and without hypertriglyceridemic waist (HTGW) and compare it with the harmonized definition of metabolic syndrome (MS) with both a higher (MS-I) and lower waist circumference (MS-II) for Europids. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women) into our cross-sectional study. The subjects with HTGW had an atherogenic lipid profile (significantly higher triglycerides, AIP, non-HDL-C, lower HDL-C and ApoA-1, and the women also higher TC and ApoB), increased markers of insulin resistance (insulin, HOMA, C-peptide, proinsulin), inflammation (hsCRP), thrombosis (fibrinogen, PAI-1), SBP and DBP, and lower adiponectin (p<0.05-0.001 for all). These risk factors were entirely similar in HTGW, MS-I and MS-II. Age-adjusted IMT was significantly higher only in the women with HTGW but this significance disappeared after further adjustment for TC, SBP, and smoking. Our results support the routine use of HTGW as a simple and inexpensive screening tool to detect subjects at increased cardiometabolic risk in clinical practice. PMID- 26680673 TI - Adipose tissue and atherosclerosis. AB - High-energy intake which exceeds energy expenditure leads to the accumulation of triglycerides in adipose tissue, predominantly in large-size adipocytes. This metabolic shift, which drives the liver to produce atherogenic dyslipidemia, is well documented. In addition, an increasing amount of monocytes/macrophages, predominantly the proinflammatory M1-type, cumulates in ectopic adipose tissue. The mechanism of this process, the turnover of macrophages in adipose tissue and their direct atherogenic effects all remain to be analyzed. PMID- 26680674 TI - Influence of breathing on the measurement of lipids in the myocardium by 1H MR spectroscopy. AB - The myocardium examination by MR spectroscopy is very challenging due to movements caused by the cardiac rhythm and breathing. The aim of the study was to investigate the influence of breathing on the quantitative measurement of lipid/water ratios in different groups of volunteers and different measuring protocols. We examined the lipid content of myocardium at 3T using the proton single voxel spectroscopy. Three protocols (free breathing, breath hold and the use of respiratory navigator) controlled by ECG were used for the examination of 42 adult volunteers including 14 free divers. Spectra were evaluated using jMRUI software. An average content of lipids in the healthy interventricular septum, gained by all protocols was equal to 0.6 %, which is in agreement with other published data. Based on the quality of examinations and the highest technical success, the best protocol seems to be the one containing a respiratory navigator since it is more acceptable by patients. Based on our results and the literature data we can conclude that MR spectroscopy is able to distinguish patients from controls only if their myocardial lipid content is higher than 1.6 % (mean value of lipids plus two standard deviations). PMID- 26680675 TI - The effect of ectopic fat on graft function after living kidney transplantation. AB - Renal transplantation is associated with a large number of risk factors that can have an influence on early renal graft function (ERGF). One of these factors could be the increasing number of obese kidney donors. The mechanisms of reduced ERGF in obese kidney donors are still poorly understood. To that end, we compared ERGF in recipients with body mass index (BMI), perivascular fat and plasma inflammation markers of live kidney donors. We hypothesized that the BMI of donors would negatively correlate with an average increase of glomerular filtration rate (GFR) and that it would also be associated with increased perivascular and plasma inflammation markers in the first seven days after transplantation. Between January 2013 and December 2014, some 58 living kidney transplantation pairs were included in the study. Donor and recipient demographic data, preoperative BMI, blood C-reactive protein (CRP) and adiponectin levels, perivascular adipose tissue (PAT) samples and recipient blood creatinine levels were analyzed. The median CRP of donors was 0.68 mg/l (max: 8.66 mg/l, min: 0.33 mg/l), the median of M1 macrophages (CD14+CD16+) in one gram of PAT was 5940 (max: 41 100, min: 248) and the median of adiponectin was 411 930 pg/ml (max: 14 217 000, min: 167 300) in plasma. We did not find any association between early renal graft function and the percentage of M1 macrophages in donor perirenal adipose tissue (p=0.83, r=0.03, n=58), adiponectin (p=0.65, r=0.06, n=58) or CRP (p=0.16, r=0.2, n=58) in plasma. The obesity level of donors, expressed as BMI, did not correlate with early renal graft function in the first seven days after transplantation. The associations between ERGF and plasma and perivascular fat inflammation markers were not significant. We confirmed a negative correlation between the BMI of recipients and an average increase of GFR in the first seven days after transplantation (p<0.02, r=-0.325, N=58). We confirmed a negative correlation of adiponectin plasma concentration to the BMI of donors. PMID- 26680676 TI - Strong gender-specific additive effects of the NYD-SP18 and FTO variants on BMI values. AB - The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of our study was to confirm the association between NYD-SP18 rs6971019 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the simultaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971019 SNP is related to BMI in males (2000/1 GG 28.3+/-3.7 kg/m(2) vs. +A 27.5+/-3.7 kg/m(2) P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971019 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males. PMID- 26680677 TI - Macrophage phenotypes in the adipose tissue of postmenopausal women. AB - Atherosclerosis pathology is the interplay between high intravascular LDL particle concentration and monocyte/macrophage presence within the sub endothelial space of the artery. In this project, phenotypes of macrophages connected with subclinical inflammation in adipose tissue of living kidney donors were studied. Samples of subcutaneous adipose tissue of living kidney donors (n=36) were exposed to collagenase. Stromal vascular fraction (SVF) was eluted from the samples, then labeled with monoclonal antibodies (anti-CD14 and anti calprotectin), conjugated with fluorochromes and analyzed by flow cytometry. The positive correlation between the number of total macrophages and calprotectin positive macrophages with BMI in the subcutaneous adipose tissue of postmenopausal women was demonstrated (p<0.05; R=0.43 and p<0.01; R=0.60), whereas no positive correlation in premenopausal women and men was shown. In conclusion, we documented a significant effect of BMI increase on the presence of total macrophages in adipose tissue of postmenopausal women, in contrast to premenopausal women. This difference was much more pronounced when proinflammatory macrophages with membrane-bound calprotectin were analyzed. PMID- 26680678 TI - Is the amount of coronary perivascular fat related to atherosclerosis? AB - Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety-six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyopathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68-positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in the perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in the arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group. According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself. PMID- 26680679 TI - Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen-induced liver injury in mice. AB - Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure. In APAP-induced acute liver failure, hepatocyte death and subsequent liver regeneration determines the prognosis of patients, making it necessary to identify suitable therapeutic targets based on detailed molecular mechanisms. Grb2-associated binder 1 (Gab1) adaptor protein plays a crucial role in transmitting signals from growth factor and cytokine receptors to downstream effectors. In this study, we hypothesized that Gab1 is involved in APAP-induced acute liver failure. Hepatocyte-specific Gab1 conditional knockout (Gab1CKO) and control mice were treated with 250 mg/kg of APAP. After APAP treatment, Gab1CKO mice had significantly higher mortality and elevated serum alanine aminotransferase levels compared to control mice. Gab1CKO mice had increased hepatocyte death and increased serum levels of high mobility group box 1, a marker of hepatocyte necrosis. In addition, Gab1CKO mice had reduced hepatocyte proliferation. The enhanced hepatotoxicity in Gab1CKO mice was associated with increased activation of stress-related c-Jun N-terminal kinase (JNK) and reduced activation of extracellular signal-regulated kinase and AKT. Furthermore, Gab1CKO mice showed enhanced mitochondrial translocation of JNK accompanied by an increase in the release of mitochondrial enzymes into the cytosol, which is indicative of increased mitochondrial dysfunction and subsequent nuclear DNA fragmentation. Finally, in vitro experiments showed that Gab1-deficient hepatocytes were more susceptible to APAP-induced mitochondrial dysfunction and cell death, suggesting that hepatocyte Gab1 is a direct target of APAP-induced hepatotoxicity. CONCLUSION: Our current data demonstrate that hepatocyte Gab1 plays a critical role in controlling the balance between hepatocyte death and compensatory hepatocyte proliferation during APAP-induced liver injury. PMID- 26680683 TI - Ultraviolet Keratitis: From the Pathophysiological Basis to Prevention and Clinical Management. AB - Ultraviolet keratitis is caused by the toxic effects of acute high-dose ultraviolet radiation (UVR) reflecting the sensitivity of the ocular surface to photochemical injury. The clinical syndrome presents with ocular pain, tearing, conjunctival chemosis, blepharospasm, and deterioration of vision typically several hours after exposure, lasting up to 3 days. Mountaineers, skiers, and beach recreationalists are particularly at risk to suffer from ultraviolet (UV) keratitis as the reflectivity of UVR in these environments is extremely high. The aim of this review is to raise awareness about the potential of UV damage on the eye with an emphasis on UV keratitis, to highlight the pathophysiological basis of corneal phototoxicity, and to provide practical guidance for the prevention and clinical management of UV keratitis commonly known as snow blindness. PMID- 26680680 TI - The Brain Symptom and Impact Questionnaire in brain metastases patients: a prospective long-term follow-up study. AB - AIMS: To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. PATIENTS & METHODS: Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow ups. RESULTS: Thirty-six patients completed all follow-ups. BASIQ correlated well (r >= 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. CONCLUSION: The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires. PMID- 26680685 TI - [Is drug promotion ethical in Peru?]. PMID- 26680684 TI - Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment. AB - In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 +/- 5 years, body-mass index: 24.9 +/- 1.6 kg/m(2); mean +/- SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 +/- 2.7 minutes), methazolamide (+1.4 +/- 1.7 minutes), and aminophylline (+1.8 +/- 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 +/- 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% +/- 3% vs. 79% +/- 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude. PMID- 26680686 TI - Complete mitochondrial genome of the golden drum Chrysochir aurenus (Perciformes, Sciaenidae) and its phylogeny. AB - The golden drum (Chrysochir aurenus) is an important food fish of Indo-West Pacific and China. To study the phylogenetic status, we sequenced the complete mitochondrial genome of C. aurenus. The mitogenome is 16 505 bp in length and composed of 13 protein-coding genes, 2 rRNAs, 22 tRNAs, and a control region. The gene composition and the structural arrangement of C. aurenus complete mtDNA were identical to most of other vertebrates. The phylogenetic analysis using the complete mitochondrial genome revealed that the C. aurenus might be grouped in different genera of Argyrosominae, but not belonged to Otolithinae, which was highly consistent with that based on the morphology. The present study will be helpful for the evolution and conservation genetic studies of C. aurenus. PMID- 26680687 TI - The global economic and regulatory determinants of household food waste generation: A cross-country analysis. AB - Food is generally wasted all along the supply chain, with an estimated loss of 35percent generated at the consumer level. Consequently, household food waste constitutes a sizable proportion of the total waste generated throughout the food supply chain. Yet such wastes vary drastically between developed and developing countries. Using data collected from 44 countries with various income levels, this paper investigates the impact of legislation and economic incentives on household food waste generation. The obtained results indicate that well-defined regulations, policies and strategies are more effective than fiscal measures in mitigating household food waste generation. PMID- 26680688 TI - Characterization of the biosolids composting process by hyperspectral analysis. AB - Composted biosolids are widely used as a soil supplement to improve soil quality. However, the application of immature or unstable compost can cause the opposite effect. To date, compost maturation determination is time consuming and cannot be done at the composting site. Hyperspectral spectroscopy was suggested as a simple tool for assessing compost maturity and quality. Nevertheless, there is still a gap in knowledge regarding several compost maturation characteristics, such as dissolved organic carbon, NO3, and NH4 contents. In addition, this approach has not yet been tested on a sample at its natural water content. Therefore, in the current study, hyperspectral analysis was employed in order to characterize the biosolids composting process as a function of composting time. This goal was achieved by correlating the reflectance spectra in the range of 400-2400nm, using the partial least squares-regression (PLS-R) model, with the chemical properties of wet and oven-dried biosolid samples. The results showed that the proposed method can be used as a reliable means to evaluate compost maturity and stability. Specifically, the PLS-R model was found to be an adequate tool to evaluate the biosolids' total carbon and dissolved organic carbon, total nitrogen and dissolved nitrogen, and nitrate content, as well as the absorbance ratio of 254/365nm (E2/E3) and C/N ratios in the dry and wet samples. It failed, however, to predict the ammonium content in the dry samples since the ammonium evaporated during the drying process. It was found that in contrast to what is commonly assumed, the spectral analysis of the wet samples can also be successfully used to build a model for predicting the biosolids' compost maturity. PMID- 26680689 TI - Melatonin: the dawning of a treatment for fibrosis? AB - Fibrosis is a common occurrence following organ injury and failure. To date, there is no effective treatment for this condition. Melatonin targets numerous molecular pathways, a consequence of its antioxidant and anti-inflammatory actions that reduce excessive fibrosis. Herein, we review the multiple protective effects of melatonin against fibrosis. There exist four major phases of the fibrogenic response including primary injury to the organ, activation of effector cells, the elaboration of extracellular matrix (ECM) and dynamic deposition. Melatonin regulates each of these phases. Additionally, melatonin reduces fibrosis levels in numerous organs. Melatonin exhibits its anti-fibrosis effects in heart, liver, lung, kidney, and other organs. In addition, adhesions which occur following surgical procedures are also inhibited by melatonin. The information reviewed here should be significant to understanding the protective role of melatonin against fibrosis, contribute to the design of further experimental studies related to melatonin and the fibrotic response and shed light on a potential treatment for fibrosis. PMID- 26680690 TI - The northern limit of corals of the genus Acropora in temperate zones is determined by their resilience to cold bleaching. AB - The distribution of corals in Japan covers a wide range of latitudes, encompassing tropical to temperate zones. However, coral communities in temperate zones contain only a small subset of species. Among the parameters that determine the distribution of corals, temperature plays an important role. We tested the resilience to cold stress of three coral species belonging to the genus Acropora in incubation experiments. Acropora pruinosa, which is the northernmost of the three species, bleached at 13 degrees C, but recovered once temperatures were increased. The two other species, A. hyacinthus and A. solitaryensis, which has a more southerly range than A. pruinosa, died rapidly after bleaching at 13 degrees C. The physiological effects of cold bleaching on the corals included decreased rates of photosynthesis, respiration, and calcification, similar to the physiological effects observed with bleaching due to high temperature stress. Contrasting hot bleaching, no increases in antioxidant enzyme activities were observed, suggesting that reactive oxygen species play a less important role in bleaching under cold stress. These results confirmed the importance of resilience to cold stress in determining the distribution and northern limits of coral species, as cold events causing coral bleaching and high mortality occur regularly in temperate zones. PMID- 26680691 TI - Chronic granulomatous disease: Clinical, molecular, and therapeutic aspects. AB - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the genes encoding any of the NADPH oxidase components responsible for the respiratory burst of phagocytic leukocytes. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes encoding p22(phox) , p47(phox) , p67(phox) , and p40(phox) , respectively. Patients suffering from this disease are susceptible to severe life-threatening bacterial and fungal infections and excessive inflammation characterized by granuloma formation in any organ, for instance, the gastrointestinal and genitourinary tract. An early diagnosis of and the prompt treatment for these conditions are crucial for an optimal outcome of affected patients. To prevent infections, CGD patients should receive lifelong antibiotics and antifungal prophylaxis. These two measures, as well as newer more effective antimicrobials, have significantly modified the natural history of CGD, resulting in a remarkable change in overall survival, which is now around 90%, reaching well into adulthood. At present, hematopoietic stem cell transplantation (HSCT) is the only definitive treatment that can cure CGD and reverse organ dysfunction. Timing, donor selection, and conditioning regimens remain the key points of this therapy. In recent years, gene therapy (GT) for XR-CGD has been proposed as an alternative to HSCT for CGD patients without a matched donor. After the failure of the first trials performed with retroviral vectors, some groups have proposed the use of regulated SIN-lentiviral vectors targeting gp91(phox) expression in myeloid cells to increase the safety and efficacy of the GT protocols. PMID- 26680693 TI - Reviewing risks and benefits of low-dose computed tomography screening for lung cancer. AB - Lung cancer is the third most common cancer among men and women and is one of the leading causes of cancer-related mortality. Diagnosis at an early stage has been suggested crucial for improving survival in individuals at high-risk of lung cancer. One potential facilitator to early diagnosis is low-dose computed tomography (LDCT). The United States Preventive Services Task Force guidelines call for annual LDCT screening for individuals at high-risk of lung cancer. This recommendation was based on the effectiveness of LDCT in early diagnosis of lung cancer, as indicated by the findings from the National Lung Screening Trial conducted in 2011. Although lung cancer accounts for more than a quarter of all cancer deaths in the United States and LDCT screening shows promising results regarding early lung cancer diagnosis, screening for lung cancer remains controversial. There is uncertainty about risks, cost-effectiveness, adequacy of evidence, and application of screening in a clinical setting. This narrative review provides an overview of risks and benefits of LDCT screening for lung cancer. Further, this review discusses the potential for implementation of LDCT in clinical setting. PMID- 26680694 TI - Erratum: Simultaneous excitation and emission enhancements in upconversion luminescence using plasmonic double-resonant gold nanorods. PMID- 26680692 TI - Association of telomere length and mitochondrial DNA copy number with risperidone treatment response in first-episode antipsychotic-naive schizophrenia. AB - Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naive SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (N = 46) and Non-Responders (N = 43) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (beta = -0.108, p = 0.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (beta = -0.178, p = 0.001), and longer telomere length (beta = 0.111, p = 0.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial eta(2) = 0.125, p = 0.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients. PMID- 26680695 TI - Birth weight predicted baseline muscular efficiency, but not response of energy expenditure to calorie restriction: An empirical test of the predictive adaptive response hypothesis. AB - OBJECTIVES: Aiming to test the evolutionary significance of relationships linking prenatal growth conditions to adult phenotypes, this study examined whether birth size predicts energetic savings during fasting. We specifically tested a Predictive Adaptive Response (PAR) model that predicts greater energetic saving among adults who were born small. METHODS: Data were collected from a convenience sample of young adults living in Albuquerque, NM (n = 34). Indirect calorimetry quantified changes in resting energy expenditure (REE) and active muscular efficiency that occurred in response to a 29-h fast. Multiple regression analyses linked birth weight to baseline and postfast metabolic values while controlling for appropriate confounders (e.g., sex, body mass). RESULTS: Birth weight did not moderate the relationship between body size and energy expenditure, nor did it predict the magnitude change in REE or muscular efficiency observed from baseline to after fasting. Alternative indicators of birth size were also examined (e.g., low v. normal birth weight, comparison of tertiles), with no effects found. However, baseline muscular efficiency improved by 1.1% per 725 g (S.D.) increase in birth weight (P = 0.037). CONCLUSIONS: Birth size did not influence the sensitivity of metabolic demands to fasting-neither at rest nor during activity. Moreover, small birth size predicted a reduction in the efficiency with which muscles convert energy expended into work accomplished. These results do not support the ascription of adaptive function to phenotypes associated with small birth size. (c) 2015 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:484-492, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26680696 TI - The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5. AB - Endocytosis is differentially regulated by hypoxia-inducible factor-1alpha (HIF 1alpha) and phospholipase D (PLD). However, the relationship between HIF-1alpha and PLD in endocytosis is unknown. HIF-1alpha is degraded through the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) ubiquitination pathway in an oxygen dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1alpha independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1alpha, PHD and VHL may contribute to EGFR endocytosis. The pleckstrin homology domain (PH) of PLD1 itself promotes degradation of HIF-1alpha, then accelerates EGFR endocytosis via upregulation of rabaptin-5 and suppresses tumor progression. These findings reveal a novel role of the PLD1-PH domain as a positive regulator of endocytosis and provide a link between PLD1 and HIF-1alpha in the EGFR endocytosis pathway. PMID- 26680697 TI - Comparison of six Aspergillus-specific IgG assays for the diagnosis of chronic pulmonary aspergillosis (CPA). AB - OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is estimated to affect 3 million persons worldwide. Aspergillus-specific IgG is a key component in CPA diagnosis. We aimed to establish the optimal diagnostic cut offs for CPA and the comparative performance of six assays in this context. METHODS: Sera from 241 patients with CPA and 100 healthy blood donors were tested using five Aspergillus specific IgG assays plus precipitin testing using Microgen Aspergillus antigens. RESULTS: Receiver operating characteristic (ROC) curve area under the curve (AUC) results were as follows: ThermoFisher Scientific ImmunoCAP 0.996 (95% confidence interval 0.992-1), Siemens Immulite 0.991 (0.982-1), Serion 0.973 (0.960-0.987), Dynamiker 0.918 (0.89-0.946) and Genesis 0.902 (0.871-0.933). Optimal CPA diagnostic cut-offs were; ImmunoCAP 20 mg/L (96% sensitivity, 98% specificity), Immulite 10 mg/L (96% sensitivity, 98% specificity), Serion 35 U/ml (90% sensitivity, 98% specificity), Dynamiker 65 AU/ml (77% sensitivity, 97% specificity) and Genesis 20 U/ml (75% sensitivity, 99% specificity). The precipitin test was 59% sensitive and 100% specific. CONCLUSIONS: ImmunoCAP and Immulite were statistically significantly superior to the other assays. Precipitins testing performed poorly. The currently accepted ImmunoCAP cut-off of 40 mg/L appears sub-optimal for CPA diagnosis and may require revision in this context. PMID- 26680700 TI - QSRR Analysis in Characterization of Some Benzimidazole Derivatives. AB - In this paper, quantitative structure-retention relationship study has been applied in order to correlate obtained retention parameter R(M)(0) and two groups of molecular descriptors, for eleven investigated benzimidazole derivatives. Principal component analysis (PCA), followed by hierarchical cluster analysis (HCA) and multiple linear regression (MLR), was applied in order to identify the most important molecular descriptors. Mathematical models were established and the best models were further validated by leave-on-out (LOO) technique as well as by the calculation of the statistical parameters. Statistically significant models were established. PMID- 26680698 TI - Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase. AB - Cyclotides are diverse plant backbone cyclized peptides that have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization, from the cyclotide-producing plant Oldenlandia affinis. We recombinantly express OaAEP1b and find it functions preferably as a cyclase by coupling C-terminal cleavage of propeptide substrates with backbone cyclization. Interestingly, OaAEP1b cannot cleave at the N-terminal site of O. affinis cyclotide precursors, implicating additional proteases in cyclotide biosynthesis. Finally, we demonstrate the broad utility of this enzyme by cyclization of peptides unrelated to cyclotides. We propose that recombinant OaAEP1b is a powerful tool for use in peptide engineering applications where increased stability of peptide products is desired. PMID- 26680701 TI - Isomorphic Viscosity Equation of State for Binary Fluid Mixtures. AB - The thermodynamic behavior of the simple binary mixtures in the vicinity of critical line has a universal character and can be mapped from pure components using the isomorphism hypothesis. Consequently, based upon the principle of isomorphism, critical phenomena and similarity between P-rho-T and T-eta (viscosity)-P relationships, the viscosity model has been developed adopting two cubic, Soave-Redlich-Kwong (SRK) and Peng-Robinson (PR), equations of state (EsoS) for predicting the viscosity of the binary mixtures. This procedure has been applied to the methane-butane mixture and predicted its viscosity data. Reasonable agreement with the experimental data has been observed. In conclusion, we have shown that the isomorphism principle in conjunction with the mapped viscosity EoS suggests a reliable model for calculating the viscosity of mixture of hydrocarbons over a wide pressure range up to 35 MPa within the stated experimental errors. PMID- 26680699 TI - Family-centered prevention ameliorates the longitudinal association between risky family processes and epigenetic aging. AB - BACKGROUND: Research has suggested that 'risky' family processes have unforeseen negative consequences for health later in life. The purpose of this study was to further understanding of risky family environments and development of health vulnerabilities by (a) examining the likelihood that elevated levels of parental depressive symptoms when children are age 11 forecast accelerated epigenetic aging 9 years later at age 20; (b) determining whether participation in an efficacious family-centered prevention program focused on enhancing supportive parenting and strengthening family relationships will ameliorate this association; and (c) testing a moderation-mediation hypothesis that prevention induced reductions in harsh parenting across adolescence will account for prevention effects in reducing accelerated epigenetic aging. METHODS: In the rural southeastern United States, parents and 11-year-old children from 399 families participated in the Strong African American Families (SAAF) program or a control condition. Parents reported their own depressive symptoms when their children were 11, and both youths and parents reported youth exposure to harsh parenting at ages 11 and 16. Blood was drawn from youths at age 20 to measure accelerated epigenetic aging using a marker derived from the DNA methylation of cells. RESULTS: Elevated parental depressive symptoms forecast accelerated epigenetic aging among youths in the control condition, but not among SAAF participants. Moderated-mediation analyses confirmed that reductions in harsh parenting accounted for SAAF's protective effects on epigenetic aging. Subsequent exploratory analyses indicated that accelerated epigenetic aging forecast emotional distress among young adults in the control condition but not among those who participated in SAAF. CONCLUSIONS: This study is unique in using a randomized prevention trial to test hypotheses about the ways risky family processes contribute to accelerated epigenetic aging. The results suggest that developmentally appropriate family-centered interventions designed to enhance parenting and strengthen families can buffer the biological residue of life in a risky family. PMID- 26680702 TI - Metabolomic Analysis of Diapausing and Noni-diapausing Larvae of the European Corn Borer Ostrinia nubilalis (Hbn.) (Lepidoptera: Crambidae). AB - In this study, an (1)H-NMR -based metabolomic approach was used to investigate the biochemical mechanisms of diapause and cold hardiness in diapausing larvae of the European corn borer Ostrinia nubilalis. Metabolomic patterns in polar hemolymph extracts from non-diapausing and diapausing larvae of O. nubilalis were compared. Analysis indicated 13 metabolites: 7 amino acids, glycerol, acetate, citrate, succinate, lactate and putrescine. Results show that diapausing larvae display different metabolomic patterns compared to active non-diapausing larvae, with predominant metabolites identified as glycerol, proline and alanine. In specific diapausing larvae initially kept at 5 ? degrees C then gradually chilled to -3 degrees C and -16 degrees C, alanine , glycerol and acetate were predominant metabolites. (1)H-NMR spectroscopy provides new insight into the metabolomic patterns associated with cold resistance and diapause in O. nubilalis larvae, suggesting distinct metabolomes function in actively developing and diapausing larvae. PMID- 26680703 TI - Liquid/Single Crystal Structure Analysis: Synthesis and Characterization of a Trimethylsilyl Derived Rod Shaped Mesogen. AB - 4-[4'-Cyanophenoxy-carbonyl-phenyl-4-(trimethylsilyl)ethynyl]benzoate a rod shaped liquid crystal (SmA) is synthesized and characterized. The single-crystals were grown in triclinic crystal system in the space group of Pi - with unit cell parameters a = 5.9577(2) A, b = 8.0398(3) A, c = 25.8842(9) A, alpha = 86.096(2)o, beta = 89.912(2)o, gamma = 2.919(2)o, Z = 2, and V = 1182.16(7). The crystal structure is stabilized by C-H...O intra-molecular interactions. Further, the structure also involves C-H...pi interactions and weak pi-pi stacking interactions [centroid-centroid separation = 3.806 (3) A]. PMID- 26680704 TI - Application of "Click" Chemistry in Solid Phase Synthesis of Alkyl Halides. AB - A convenient and highly selective microwave assisted procedure for the conversion of allylic, benzylic and aliphatic alcohols to their corresponding halide using polymer-bound triphenylphosphine and iodine is presented. In case of symmetrical diols, mono-iodination product is obtained in very high yield. Additionally, high regioselective behavior is observed in our procedure. Simplicity in operation, no column chromatography requirement for purification of the product, recyclability of the reagents used, short reaction times and good to excellent yields are the advantages of our protocol. Most functional groups remain unaffected under our reaction condition. PMID- 26680705 TI - Prediction of Stability Constants of Zinc(II) Complexes with 2-aminobenzamide and Amino Acids. AB - We developed a model for the stability (log beta(ZnLB)) of Zn(2+) mixed complexes (N = 16) with 2-aminobenzamide (L) and four amino acids (B) glycine, alanine, valine, and phenylalanine at 300, 310, 320, and 330 K. The model was based on the quadratic regression function of the molecular valence connectivity index of the third order, (3)chi(v), yielded S.E. = 0.02. We also developed an overall model for K(1), K(2) and beta(ZnLB) of the same system at all of the four temperatures (N= 48). This model yielded S.E. = 0.05. PMID- 26680706 TI - Influence of the Synthesis Parameters on the Properties of NaYF4:Yb3+,Tm3+ Nanoparticles. AB - Fluorescent nanoparticles, especially fluorides, have received a great deal of interest due to their optical properties, making them suitable for applications in bio-imaging. For this reason they need to exhibit a superior chemical stability in aqueous media. We have studied the influence of the synthesis parameters on the chemical stability of NaYF(4) nanoparticles co-doped with Yb(3+) and Tm(3+). These nanoparticles have different crystal structures, and were synthesized hydrothermally or with thermal decomposition. The samples were characterized with X-ray diffraction and transmission electron microscopy. The up conversion fluorescence of nanoparticles dispersed in water was measured at 400 900 nm. The partial dissolution of the fluorine in water was detected with an ion selective electrode for all the samples. The dissolution of the other constituent ions was analysed with an optical emission spectrometer using inductively coupled plasma. The nanoparticles with a hexagonal crystal structure and sizes of around 20 nm that were synthesized with thermal decomposition showed a superior chemical stability in water together with a superior up-conversion fluorescence yield. PMID- 26680707 TI - Preparation and Electrochemical Characterization of Aluminium Liquid Battery Cells With Two Different Electrolytes (NaCl-BaCl2-AlF3-NaF and LiF-AlF3-BaF2). AB - The possibility of preparation of operating rechargeable liquid battery cells based on aluminium and its alloys is systematically checked. In all cases we started from aluminium as the negative electrode whereas as the positive electrode three different metals were tested: Pb, Bi and Sn. Two types of electrolytes were selected: Na(3)AlF(6) -AlF(3) - BaCl(2) - NaCl and Li(3)AlF(3) BaF(2). We show that some of these combinations allowed efficient separation of individual liquid layers. The cells exhibited expected voltages, relatively high current densities and could be charged and discharged several times. The capacities were relatively low (120 mAh in the case of Al-Pb system), mostly due to unoptimised cell construction. Improvements in various directions are possible, especially by hermetically sealing the cells thus preventing salt evaporation. Similarly, solubility of aluminium in alloys can be increased by optimising the composition of positive electrode. PMID- 26680708 TI - Synthesis, Characterization, Spectral Studies, Antibacterial Evaluation, Thermodynamics and DFT Calculations of Dimethyltin(IV) Dichloride Schiff Base. AB - A number of new 1:1 complexes of SnMe(2)Cl(2) with unsymmetrical tetradentate Schiff base ligand with NNOS coordination sphere have been synthesized and fully characterized by a variety of physico-chemical techniques viz. elemental analysis, molar conductivity, (1)H and (119)Sn NMR, IR and mass spectroscopy. IR spectral data show that the fifth coordination position of tin atom is occupied by an oxygen atom of Schiff base ligands. In the light of titled techniques, trigonal bipyramidal geometry around the tin atom is proposed for the synthesized complexes. The in vitro antibacterial activities of the complexes against Staphylococcus aureus and Escherichia Coli have been studied. It was found that they possess significant antibacterial activity. Also, DFT/B3LYP method was used to analyze the electronic structures and study of the geometries. The thermodynamic formation constants of the complexes were determined spectrophotometrically at 25oC in DMF solvent. PMID- 26680709 TI - Anaerobic Biodegradation of Raw and Pre-treated Brewery Spent Grain Utilizing Solid State Anaerobic Digestion. AB - The brewery spent grain (BSG) represents approximately 85% of the total quantity of by-products from the brewing industry. The biogas production from the BSG has been the subject of several studies in recent years, due to relatively high energy consumption in the brewing process and due to the increasing energy costs. The biodegradability of raw and pre-treated BSG in a single-stage and two-stage solid-state anaerobic digestion (SS-AD) system was determined in this study. The results show that the BSG have a biogas potential of 120 L/kg(-1). In the single stage system, the biogas yield obtained from raw BSG (87.4 L/kg(-1)) was almost equal to the yield obtained from the pre-treated BSG (89.1 L/kg(-1)), while the methane yield was 51.9 and 55.3 L/kg(-1) and the biodegradation was 62.0% and 62.2% for raw and pre-treated BSG, respectively. In two-stage SS-AD the pre treated BSG showed better results, with the biogas yield of 103.2 L/kg(-1) and the biodegradation of 73.6%, while the biogas yield obtained from raw BSG was 89.1 L/kg(-1), with the biodegradation of 63.5%. In two-stage process the obtained methane yields from raw and pre-treated BSG were identical (58.7 L/kg( 1)). PMID- 26680711 TI - Composition of Organic Compounds Adsorbed on PM10 in the Air Above Maribor. AB - Organic compounds in atmospheric particulate matterabove Maribor were analysed in 120 samples of PM10 sampled according to the EN 12341:2014 reference method. Organic compounds compositions were investigated together with the primary and secondary sources of air pollution. Silylation as derivatisation method was used for the GC/MS determination of volatile and semi-volatile polar organic compounds. Distribution of fatty acids, n-alkanes and iso-alkanes, phthalate esters, siloxanes, different sterols, various sugars and sugar alcohols, compounds of lignin and resin acids, dicarboxylic acids from photochemical reactions, PAHs, organic nitrogen compounds and products from secondary oxidation of monoterpenes were determined. The use of silicone grease for the purpose of lubricating the impact surface of the air sampler caused higher values of gravimetric determination. Solid particles may have been bounced from the surface of a greasy impact plate and re-entrained within the air stream and then collected on a sample filter. The carryover of siloxanes was at least from 5% up to 15% of the accumulated particles weight, depending on ambient temperature. This was the reason that the gravimetric results for determination of PM10 according to the standard EN 12341:2014 were overestimated. PMID- 26680710 TI - Synthesis and Crystal Structures of Benzohydroxamate-Coordinated Vanadium(V) Oxo Complexes with Aroylhydrazone Ligands. AB - Reaction of [VO(acac)(2)] (where acac = acetylacetonate), benzohydroxamic acid (Hbha), and two similar aroylhydrazone ligands in methanol produced two benzohydroxamate-coordinated mononuclear vanadium(V) oxo complexes with general formula [VOL(bha)], where L = L(1) = N'-(5-bromo-2-hydroxybenzylidene)-2 fluorobenzohydrazide (H(2)L(1)), and L = L(2) = N'-(3-bromo-2-hydroxybenzylidene) 2-fluorobenzohydrazide (H(2)L(2)). Crystal and molecular structures of the complexes were determined by single crystal X-ray diffraction method. All of the investigated compounds were further characterized by elemental analysis, and FT IR and UV-Vis spectra. Single crystal X-ray structural studies indicate that the benzohydrazone ligands coordinate to the VOcores through phenolate O, imino N, and enolate O atoms, and the benzohydroxamate ligands coordinate to the VO cores through deprotonated hydroxyl O and carbonyl O atoms. The V atoms in both complexes are in octahedral coordination. Thermal stability of the complexes was studied. PMID- 26680712 TI - Surfactant Assisted Sonochemical Synthesis and Characterization of Gadolinium Doped Zinc Oxide Nanoparticles. AB - Pure and Gd doped Zinc Oxide (ZnO) nanoparticles were synthesized by sonochemical method using different surfactants (PVP/CTAB). The nanoparticles were characterized by powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), particle size analysis by DLS technique and UV-Visible spectroscopy. The effect of Gd doping and nature of surfactants on crystallite size, morphology and band gap of ZnO nanoparticles have been investigated. In addition to this, the effect of nature of surfactant on amount of dopant inserted in the ZnO lattice was also studied. PMID- 26680713 TI - Improving Drinking Water Quality by Remineralisation. AB - The reason of low mineral content in source water is its origin in poorly soluble mineral geological structures. There are many areas with very soft low mineralised water around the world. All people involved in drinking water treatment as well as some public health experts and producers of chemicals used for water treatment may be interested in the study. Enrichment of drinking water by minerals including calcium and magnesium is very important particularly in regions where drinking water is prepared by desalination. The aim of this work was to study and intensify the recarbonization process. Half-calcined dolomite in combination with carbon dioxide constitutes the chemistry of the applied method. Advantages of using a fluidised bed reactor contributed also significantly to the process efficiency enhancement. Continuous input of carbon dioxide into the fluidised bed recarbonization reactor resulted in an increase in the recarbonization rate by about one order of magnitude compared with the process in without carbon dioxide addition. Very good fit of experimental data for hydrodynamic characteristics of fluidised bed was obtained using simple model based on the Richardson and Zaki expansion equation. The first order model describes kinetic data from the recarbonization process with a good accuracy. Higher recarbonization rates were observed with smaller particles of half calcined dolomite. PMID- 26680714 TI - Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors. AB - A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III. PMID- 26680715 TI - Elements of an Universal Matrix as Topological Indices for Physicochemical Properties of Octanes. AB - Some of the elements of the Universal matrix and their combinations are useful topological indices of physicochemical properties of octanes. Whereas single elements of the Universal matrix give rise to 0.70 < R < 0.99, mutually optimized combinations of only four to six out of 56 of them in the Universal matrix of octanes give rise to R > 0.99 and in the worst cases to R > 0.98. Also a new measure of goodnes of correlation, the Amount of information in the topological index, Ainfo (%), is introduced. Structural interpretation of some of the physicochemical properties of octanes is demonstrated as well as of the contribution by the most useful elements of the Universal matrix. PMID- 26680716 TI - Kinetics and Mechanism of the Ligand Exchange Reaction Between Tetraaza Macrocycle Ligand and Cu(II) Tetradentate Amine-Amide Complexes. AB - The kinetics of the ligand exchange reaction of tetraaza macrocycle, teazma (teazmais 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene dihydrogen perchlorate) with Cu(bcen)(2+) and Cu(bctn)(2+), where bcen and bctn are N,N'-bis(beta-carbamoylethyl) ethylendiamine) and N,N'-bis(beta carbamoylethyl) propylendiamine), respectively, have been studied by visible spectrophotometry in dimethylformamide, DMF, solvent at 25 +/- 0.2 degrees C. In the system of Cu(bctn)(2+)/teazma,the ligand exchange reaction proceeds in a two step-consecutive manner, with two rate constants k(bctn)(obsd)(1) and k(bctn)(obsd)(2). The first reaction step was dependent on the concentration of teazma macrocycle, while the second reaction step was independent. However, it is found that the ligand exchange reaction in Cu(bcen)(2+)/teazma proceeds in an one step with the rate constant k(bcen)(obsd). The rate constant is dependent on [teazma] macrocycle. The ligand exchange reaction in the system of Cu(bcen)(2+)/teazma is not complete and after some progress, the reaction reaches equilibrium. On the basis of results, a reaction mechanism is proposed and discussed for the ligand exchange rate. PMID- 26680717 TI - Synthesis and Electrochemical Characterization of Graphene Nanoribbon stacks Functionalized with Buckyballs. AB - Graphene nanoribbons were prepared from commercially-available multi-walled carbon nanotubes and in situ functionalized with C(60) - buckyballs. The physical properties of the synthesized functionalized material were analyzed by scanning electron microscopy, transmission electron microscopy, evolved gas analysis and Raman spectroscopy, and were compared to non-functionalized material. Further, electrochemical characterization was done to evaluate the redox-activity and capacity of the material in Li-ion batteries. Comparison to non-functionalized material shows improved capacity at lower current densities. PMID- 26680718 TI - The Fabrication of ZnO Microrods on Monolayer Graphene and Their Photocatalytic Application. AB - Zinc oxide (ZnO) microrods were fabricated on graphene/SiO(2)/Si substrate by a simple hydrothermal route. The obtained products were characterized using X-ray powder diffraction, scanning electron microscopy, energy dispersive X-ray spectrometry, photoluminescence and UV-visible spectrometry. Microrods exhibits hexagonal wurzite structure. Some ZnO clusters and twinned ZnO structures were found spread on the microrod array layer. The formation mechanism of ZnO microrods is discussed, emphasizing the formation mechanism of isolated clusters and twinned ZnO structures. Furthermore, microrods demonstrated a good photocatalytic performance towards rhodamine B degradation as ascribed to oxygen vacancies and interstitials considered as the photocatalytical active sites. PMID- 26680719 TI - Computational Thermo-chemical Study of Enthalpies of formation of beta Alkylthiophenes Using Ab Initio and DFT Calculations. AB - The values for the standard molar enthalpies of formation of a series of the B ring position alkyl-substituted thiophenes are calculated at 298.15 K using the Hartree-Fock (HF) and density functional theory (DFT) techniques. The results obtained are discussed in term of the substituent effect on the structural, electronic, and energetics of the titled molecules. The alkyl substitution with electron donating plays a fine-tune effect on the geometries, electronics, and energetics of the species. In the atomization energy route, the standard enthalpies of formation in the gas-phase, DHo(f,298)(g), obtained using the B3LYP/6-31G(d,p) method, can be successfully correlated to the substituent length via a linear dependence. However, DHo(f,298)(g), obtained using the HF/6-31G(d,p) method, is not able to predict their experimental behavior. In the formation reaction route, both the DFT and HF calculations reveal the same trend for predicting the values for the standard enthalpies of formation in the condensed phase. It could be anticipated that the calculations can be extended to estimate the relative thermodynamic stabilities of oligo- and polymers consisting of this building blocks. PMID- 26680720 TI - Synthesis, Crystal Structure, Photophysical Properties and Theoretical Study of a New Iridium(III) Complex Containing 2-phenylbenzothiazole Ligand. AB - A new bis-cyclometalated iridium(III) complex [Ir(dmabt)(2)(bipy)][PF(6)] (3) (dmabt = 4-(benzo[d]thiazol-2-yl)-N,N-dimethylaniline, bipy = 2,2'-bipyridine) has been synthesized and fully characterized. The complex 3 has been determined by X-ray structure analyses which shows that the central iridium(III) ion assumes distorted octahedral geometry. The photoluminescence spectrum exhibits orange emission maximum at 612 nm with quantum yield of 17% at 298 K. The frontier molecular orbital diagrams and the spin-allowed singlet-singlet electronic transitions of 3 have been calculated with density functional theory (DFT) and time-dependent DFT (TD-DFT), and the UV-Vis spectra are discussed based on the theoretical calculations. PMID- 26680721 TI - Simple, Rapid and Selective Chronopotentiometric Method for the Determination of Riboflavin in Pharmaceutical Preparations Using a Glassy Carbon Electrode. AB - A novel, simple, sensitive and reliable electrochemical method for the riboflavin determination using chronopotentiomery with glassy carbon electrode was developed. The most important instrumental parameters of chronopotentiometry including type and concentration of supporting electrolyte, initial potential and current range were examined and optimised in respect to riboflavin analytical signal. Riboflavin provided well defined reduction signal at -0.12 V vs. Ag/AgCl (3.5 mol/L KCl) electrode in 0.025 mol/L HCl. Under optimal conditions, linear response of riboflavin was observed in the concentration range of 0.2 - 70 mg/L with achieved limit of detection of 0.076 mg/L and limit of quantitation of 0.23 mg/L of riboflavin. Common vitamins and filing materials did not interfere in the determination. The proposed method was successfully applied for determination of riboflavin in commercially available pharmaceutical preparations. The obtained results were in statistical agreement to the contents declared by manufacturer and to those obtained by HPLC used as comparative method. PMID- 26680722 TI - Effect of Solid State Fermentation Medium Optimization on Pleurotus ostreatus Laccase Production. AB - The objective of this work was to increase laccase production by Pleurotus ostreatus PLAB through culture medium optimization using solid state culture conditions. Increased laccase activity was obtained through design of experiments (DOE) using the Taguchi orthogonal array (OA). Seven factors, viz. lignocellulose, glucose, yeast extract, peptone, KH(2)PO(4), MgSO(4) 7H(2)O and MnSO(4) H(2)O at three levels and pH at two levels. OA layout of L18 (2(1) x 3(7)) was selected for the proposed experimental design using Minitab 17 software. Data analysis showed that lignocellulose (20 %) and glucose (10 g L1) had positive effect, whereas KH(2)PO(4), MgSO(4)?7H(2)O and MnSO(4)?H(2)O did not have significant effect on laccase production. Taguchi OA analysis showed that pH 6, lignocellulose 20 %, glucose 10 g L(-1), yeast extract 6 g L(-1), peptone 15 g L(-1), KH(2)PO(4) 3 g L1, MgSO(4)?7H(2)O 0.5 g L(-1) and MnSO(4)?H(2)O 0.1 g L-1 were the optimal conditions to maximize laccase production. The model predicted a 30.37 U g(-1) dry wt., which agreed with the experimentally obtained laccase activity 29.15 U g(-1) dry wt. at optimal conditions. PMID- 26680723 TI - Synthesis, Crystal Structures and Urease Inhibition of N'-(2-Bromobenzylidene)-2 (4-nitrophenoxy) acetohydrazide and N'-(4-Nitrobenzylidene) -2-(4 nitrophenoxy)acetohydrazide. AB - Two new hydrazone compounds, N'-(2-bromobenzylidene)-2-(4 nitrophenoxy)acetohydrazide (1) and N'-(4-nitrobenzylidene)-2-(4 nitrophenoxy)acetohydrazide (2), were prepared and structurally characterized by elemental analysis, IR, UV-Vis and (1)H NMR spectroscopy, and single-crystal X ray diffraction. Compound 1 crystallizes in the monoclinic space group P2(1)/n with unit cell dimensions of a = 5.3064(5) A, b = 18.202(2) A, c = 15.970(2) A, beta = 95.866(3)o, V = 1534.4(2) A(3), Z = 4, R(1) = 0.0457, and wR(2) = 0.0975. Compound 2 crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions of a = 4.6008(7) A, b = 14.451(2) A, c = 23.296(3) A, beta = 93.620(2)o, V = 1545.8(4) A(3), Z = 4, R(1) = 0.0441, and wR2 = 0.0985. Structures of the compounds are stabilized by hydrogen bonds and pi...pi interactions. The urease inhibitory activities of the compounds were studied. Both compounds show strong urease inhibitory activities, with IC(50) values of 8.4 and 20.2 MUM, respectively. PMID- 26680724 TI - Evaluation of Adsorption Capacity of Montmorillonite and Aluminium-pillared Clay for Pb2+, Cu2+ and Zn2. AB - Adsorption capacity of the two adsorbents was investigated as a function of contact time between adsorbent and heavy metal ions solutions, the initial heavy metals concentration of the synthetic wastewater, pH value, temperature and adsorbent mass. Preliminary experiments at different pH values between 2.0 and 7.0 were performed, and were observed that maximum adsorption occurs at pH 5 for copper (q(max) = 92.59 mg . g(-1)), 6.0 for lead (qmax = 97.08 mg . g(-1)) and 6.5 for zinc ions (q(max) = 73.52 mg . g(-1)), respectively. The sorption capacity of studied adsorbents for Pb(2+), Cu(2+) and Zn(2+) was calculated using Langmuir and Freundlich models. Thermodynamic parameters - enthalpy change (DeltaH(0)), entropychange (DeltaS(0)) and free energy (DeltaG(0)) - were calculated for predicting the nature of adsorption. Scanning electron micrograph(SEM) revealed changes in the surface morphology of the adsorbent as a result of heavy metal ions adsorption.EDS characterization confirmed qualitatively the presence of adsorbed species in the samples. On the basis of the obtained results the adsorption it was proposed an ordered adsorption: Pb(2+), Cu(2+) and Zn(2+), on the sorbents we investigated. PMID- 26680725 TI - Influence of Crystal Habit on the Dissolution of Simvastatin Single Crystals. AB - In order to achieve better in-vivo performance of the final dosage form comprising a poorly soluble drug the physicochemical properties of the active pharmaceutical ingredient can be altered not only by changing the solid state form but also through the conversion of their crystal habits. To elucidate this approach in the case of simvastatin, the dissolution behaviour of large crystals with the same internal structure but expressing different crystal habits was studied using atomic force microscope. The obtained differences in the dissolution were explained through the determination of crystal morphology its orientation and assignation of the molecular functional groups that were emerging on the surface of the dissolving crystal face. The dissolution rates of the particular crystal faces were found to be distinctly higher than others. The dissolution rate of single crystals differed as a consequence of higher incidence of more polar faces in case of rod shaped crystals isolated from more hydrophilic solvent mixture which we have established through a thorough research of the single crystal morphology, orientation and the assignation of specific functional groups for each of evolved crystal faces. PMID- 26680726 TI - ZrOCl2/nano TiO2 as an Efficient Catalyst for the One Pot Synthesis of Naphthopyranopyrimidines Under Solvent-free Conditions. AB - ZrOCl(2)/nano-TiO(2) has been used as an efficient catalyst for the preparation of naphtho[1',2':5,6]pyrano[2,3-d]pyrimidine derivatives by the three-component reaction of aldehydes, beta-naphthol and 1,3-dimethylbarbituric acid. The advantages of the reaction are solvent-free conditions, short reaction times, easy workup, good to excellent yields, and cost-effective and reusable catalyst. PMID- 26680727 TI - On Multiple Zagreb Indices of TiO2 Nanotubes. AB - The First and Second Zagreb indices were first introduced by I. Gutman and N. Trinajstic in 1972. It is reported that these indices are useful in the study of anti-inflammatory activities of certain chemical instances, and in elsewhere. Recently, the first and second multiple Zagreb indices of a graph were introduced by Ghorbani and Azimi in 2012. In this paper, we calculate the Zagreb indices and the multiplicative versions of the Zagreb indices of an infinite class of Titania nanotubes TiO(2)[m,n]. PMID- 26680728 TI - Synthesis and Characterization of Fe3O4@SiO2 NPs as an Effective Catalyst for the Synthesis of Tetrahydrobenzo[a]xanthen-11-ones. AB - In this research, the significant application of Fe(3)O(4)@SiO(2) core-shell nanoparticles as an efficient, green, robust, cost-effective and recoverable nanocatalyst for multi-component reaction of aldehydes, 2-naphthol and dimedone has been developed in aqueous ethanol media under reflux conditions. This procedure also avoids hazardous reagents/solvents, and thus can be an eco friendly alternative to the existing methods. Simple procedure, environmentally benign, excellent yields, short reaction times, simple purification and facile catalyst separation are advantages of this protocol. Characterization and structural elucidation of the products have been done on the basis of chemical, analytical and spectral analysis and also the heterogeneous nanoparticles were fully characterized by FT-IR, XRD, EDX, VSM and SEM analysis. PMID- 26680729 TI - Benzimidazole or Diamide From a Reaction of Diamines and Carboxylic Acids or Acid Chlorides: Crystal Structures and Theoretical Studies. AB - A reaction of an acid chloride with a diamine yielded a diamide. m-Toluic acid was chlorinated to m-toluoyl chloride and subsequently reacted with 4-methyl-o phenylenediamine in pyridine to obtain 3-methyl-N-[2-(3 methylbenzamido)phenylbenzamide (I). 2-(3-Methylphenyl)-1H-benzimidazole (II) has been obtained upon reacting o-phenylenediamine with m-toluic acid in polyphosphoric acid and toluene. The compounds have been characterized by IR, NMR, microanalyses and GC-MS. The crystal structures of the compounds have been discussed. DFT calculations of the frontier orbitals of the precursor compounds have been carried out to ascertain the groups that contribute to the HOMO and LUMO, and to study their contribution to the reactivity in the formation of the diamides and benzimidazoles. The synthesis of the amide from a diamine was seen to be favoured in the presence of a good leaving group attached to the carbonyl as in the case of acid chloride. However, the synthesis of benzimidazoles was found to be favoured in the presence of an excess of a protonating agent and high temperature. PMID- 26680730 TI - A new method for assessing the contribution of Primary Biological Atmospheric Particles to the mass concentration of the atmospheric aerosol. AB - Primary Biologic Atmospheric Particles (PBAPs) constitute an interesting and poorly investigated component of the atmospheric aerosol. We have developed and validated a method for evaluating the contribution of overall PBAPs to the mass concentration of atmospheric particulate matter (PM). The method is based on PM sampling on polycarbonate filters, staining of the collected particles with propidium iodide, observation at epifluorescence microscope and calculation of the bioaerosol mass using a digital image analysis software. The method has been also adapted to the observation and quantification of size-segregated aerosol samples collected by multi-stage impactors. Each step of the procedure has been individually validated. The relative repeatability of the method, calculated on 10 pairs of atmospheric PM samples collected side-by-side, was 16%. The method has been applied to real atmospheric samples collected in the vicinity of Rome, Italy. Size distribution measurements revealed that PBAPs was mainly in the coarse fraction of PM, with maxima in the range 5.6-10 MUm. 24-h samples collected during different period of the year have shown that the concentration of bioaerosol was in the range 0.18-5.3 MUg m(-3) (N=20), with a contribution to the organic matter in PM10 in the range 0.5-31% and to the total mass concentration of PM10 in the range 0.3-18%. The possibility to determine the concentration of total PBAPs in PM opens up interesting perspectives in terms of studying the health effects of these components and of increasing our knowledge about the composition of the organic fraction of the atmospheric aerosol. PMID- 26680731 TI - The complete mitochondrial genome sequence of Japanese murrelet (Aves: Alcidae) and its phylogenetic position in Charadriiformes. AB - The Japanese murrelet (Synthliboramphus wumizusume) is a threatened bird endemic to Japan, Korea, and Russia. We generated the complete mitochondrial genome sequence to provide molecular genetic information for phylogeny and conservation of the species. The S. wumizusume mitochondrial genome is 16 714 bp in length and comprises 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, a non coding control region, and a repeat region. Gene composition and order in the genome is consistent with that of other mitochondrial genomes of the order Charadriiformes currently available in the GenBank. Phylogenetic analysis using all available Charadriiform mitochondrial genomes revealed that interfamilial relationships of the birds based on mitochondrial genes were in agreement with those based on multilocus nuclear genes. The complete mitochondrial genome of S. wumizusume we sequenced might be a useful genetic resource for phylogenetic relationships, evolutionary biology, and conservation of the species. PMID- 26680732 TI - Water intake and beverage consumption of pre-schoolers from six European countries and associations with socio-economic status: the ToyBox-study. AB - OBJECTIVE: To study the quantity and quality of water intake from beverages among pre-schoolers and investigate associations with gender and socio-economic status (SES). DESIGN: Kindergarten-based cross-sectional survey within the large-scale European ToyBox-study. A standardized protocol was used and parents/caregivers filled in sociodemographic data and a semi-quantitative FFQ. SETTING: Kindergartens in six European countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain). SUBJECTS: European pre-schoolers (aged 3.5-5.5 years) and their parents/caregivers (n 7051). RESULTS: Mean water intake was 1051 ml/d; plain water, 547 ml/d; plain milk, 241 ml/d; other fruit juice, 104 ml/d; pure fruit juice, 59 ml/d; soft drinks, 55 ml/d; tea, 45 ml/d; sugared and chocolate milk, 37 ml/d; smoothies, 15 ml/d; and light soft drinks, 6 ml/d. Boys had a higher water intake than girls due to a higher consumption of plain water, but more importantly to the consumption of beverages of less quality. Lower-SES pre schoolers scored better on quantity than high-SES pre-schoolers, but as a consequence of consumption of sugared beverages. Nevertheless, the associations differed by country. CONCLUSIONS: The water intake from beverages did not meet the European Food Safety Authority standard of 1280 ml/d; especially in Western European countries water intake from beverages was low. The most important water sources were plain water, milk and fruit juices. Interventions aiming at a proper and sufficient water intake should focus on both quantity and quality. Messages about water and water sources should be clear for everyone and interventions should be sufficiently tailored. PMID- 26680733 TI - EffectorP: predicting fungal effector proteins from secretomes using machine learning. AB - Eukaryotic filamentous plant pathogens secrete effector proteins that modulate the host cell to facilitate infection. Computational effector candidate identification and subsequent functional characterization delivers valuable insights into plant-pathogen interactions. However, effector prediction in fungi has been challenging due to a lack of unifying sequence features such as conserved N-terminal sequence motifs. Fungal effectors are commonly predicted from secretomes based on criteria such as small size and cysteine-rich, which suffers from poor accuracy. We present EffectorP which pioneers the application of machine learning to fungal effector prediction. EffectorP improves fungal effector prediction from secretomes based on a robust signal of sequence-derived properties, achieving sensitivity and specificity of over 80%. Features that discriminate fungal effectors from secreted noneffectors are predominantly sequence length, molecular weight and protein net charge, as well as cysteine, serine and tryptophan content. We demonstrate that EffectorP is powerful when combined with in planta expression data for predicting high-priority effector candidates. EffectorP is the first prediction program for fungal effectors based on machine learning. Our findings will facilitate functional fungal effector studies and improve our understanding of effectors in plant-pathogen interactions. EffectorP is available at http://effectorp.csiro.au. PMID- 26680734 TI - Light-RCV: a lightweight read coverage viewer for next generation sequencing data. AB - BACKGROUND: Next-generation sequencing (NGS) technologies has brought an unprecedented amount of genomic data for analysis. Unlike array-based profiling technologies, NGS can reveal the expression profile across a transcript at the base level. Such a base-level read coverage provides further insights for alternative mRNA splicing, single-nucleotide polymorphism (SNP), novel transcript discovery, etc. However, to our best knowledge, none of existing NGS viewers can timely visualize genome-wide base-level read coverages in an interactive environment. RESULTS: This study proposes an efficient visualization pipeline and implements a lightweight read coverage viewer, Light-RCV, with the proposed pipeline. Light-RCV consists of four featured designs on the path from raw NGS data to the final visualized read coverage: i) read coverage construction algorithm, ii) multi-resolution profiles, iii) two-stage architecture and iv) storage format. With these designs, Light-RCV achieves a < 0.5s response time on any scale of genomic ranges, including whole chromosomes. Finally, a case study was performed to demonstrate the importance of visualizing base-level read coverage and the value of Light-RCV. CONCLUSIONS: Compared with multi-functional genome viewers such as Artemis, Savant, Tablet and Integrative Genomics Viewer (IGV), Light-RCV is designed only for visualization. Therefore, it does not provide advanced analyses. However, its backend technology provides an efficient kernel of base-level visualization that can be easily embedded to other viewers. This viewer is the first to provide timely visualization of genome-wide read coverage at the base level in an interactive environment. The software is available for free at http://lightrcv.ee.ncku.edu.tw. PMID- 26680735 TI - Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats. AB - Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF independent pathway. PMID- 26680736 TI - An organotypic slice model for ex vivo study of neural, immune, and microbial interactions of mouse intestine. AB - Organotypic tissue slices provide seminatural, three-dimensional microenvironments for use in ex vivo study of specific organs and have advanced investigative capabilities compared with isolated cell cultures. Several characteristics of the gastrointestinal tract have made in vitro models for studying the intestine challenging, such as maintaining the intricate structure of microvilli, the intrinsic enteric nervous system, Peyer's patches, the microbiome, and the active contraction of gut muscles. In the present study, an organotypic intestinal slice model was developed that allows for functional investigation across regions of the intestine. Intestinal tissue slices were maintained ex vivo for several days in a physiologically relevant environment that preserved normal enterocyte structure, intact and proliferating crypt cells, submucosal organization, and muscle wall composure. Cell death was measured by a membrane-impermeable DNA binding indicator, ethidium homodimer, and less than 5% of cells were labeled in all regions of the villi and crypt epithelia at 24 h ex vivo. This tissue slice model demonstrated intact myenteric and submucosal neuronal plexuses and functional interstitial cells of Cajal to the extent that nonstimulated, segmental contractions occurred for up to 48 h ex vivo. To detect changes in physiological responses, slices were also assessed for segmental contractions in the presence and absence of antibiotic treatment, which resulted in slices with lesser or greater amounts of commensal bacteria, respectively. Segmental contractions were significantly greater in slices without antibiotics and increased native microbiota. This model renders mechanisms of neuroimmune microbiome interactions in a complex gut environment available to direct observation and controlled perturbation. PMID- 26680737 TI - Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. AB - Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean delivered preterm pigs (90-92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n = 16-17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59-63%) in CON and PAR pigs (P < 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P < 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P < 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formula-fed preterm neonates. PMID- 26680738 TI - Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses. AB - The molecular mechanisms that regulate late endosomal maturation and function are not completely elucidated, and direct evidence of a calcium sensor is lacking. Here we identify a novel mechanism of late endosomal maturation that involves a new molecular interaction between the tethering factor Munc13-4, syntaxin 7, and VAMP8. Munc13-4 binding to syntaxin 7 was significantly increased by calcium. Colocalization of Munc13-4 and syntaxin 7 at late endosomes was demonstrated by high-resolution and live-cell microscopy. Munc13-4-deficient cells show increased numbers of significantly enlarged late endosomes, a phenotype that was mimicked by the fusion inhibitor chloroquine in wild-type cells and rescued by expression of Munc13-4 but not by a syntaxin 7-binding-deficient mutant. Late endosomes from Munc13-4-KO neutrophils show decreased degradative capacity. Munc13-4-knockout neutrophils show impaired endosomal-initiated, TLR9-dependent signaling and deficient TLR9-specific CD11b up-regulation. Thus we present a novel mechanism of late endosomal maturation and propose that Munc13-4 regulates the late endocytic machinery and late endosomal-associated innate immune cellular functions. PMID- 26680739 TI - Roles of septins in prospore membrane morphogenesis and spore wall assembly in Saccharomyces cerevisiae. AB - The highly conserved family of septin proteins has important functions in cytokinesis in mitotically proliferating cells. A different form of cytokinesis occurs during gametogenesis in Saccharomyces cerevisiae, in which four haploid meiotic products become encased by prospore membrane (PSMs) and specialized, stress-resistant spore walls. Septins are known to localize in a series of structures near the growing PSM, but previous studies noted only mild sporulation defects upon septin mutation. We report that directed PSM extension fails in many septin-mutant cells, and, for those that do succeed, walls are abnormal, leading to increased susceptibility to heating, freezing, and digestion by the Drosophila gut. Septin mutants mislocalize the leading-edge protein (LEP) complex required for normal PSM and wall biogenesis, and ectopic expression of the LEP protein Ssp1 perturbs mitotic septin localization and function, suggesting a functional interaction. Strikingly, extra copies of septin CDC10 rescue sporulation and LEP localization in cells lacking Sma1, a phospholipase D-associated protein dispensable for initiation of PSM assembly and PSM curvature but required for PSM extension. These findings point to key septin functions in directing efficient membrane and cell wall synthesis during budding yeast gametogenesis. PMID- 26680740 TI - An ensemble of specifically targeted proteins stabilizes cortical microtubules in the human parasite Toxoplasma gondii. AB - Although all microtubules within a single cell are polymerized from virtually identical subunits, different microtubule populations carry out specialized and diverse functions, including directional transport, force generation, and cellular morphogenesis. Functional differentiation requires specific targeting of associated proteins to subsets or even subregions of these polymers. The cytoskeleton of Toxoplasma gondii, an important human parasite, contains at least five distinct tubulin-based structures. In this work, we define the differential localization of proteins along the cortical microtubules of T. gondii, established during daughter biogenesis and regulated by protein expression and exchange. These proteins distinguish cortical from mitotic spindle microtubules, even though the assembly of these subsets is contemporaneous during cell division. Finally, proteins associated with cortical microtubules collectively protect the stability of the polymers with a remarkable degree of functional redundancy. PMID- 26680743 TI - g-FLUA2H: a web-based application to study the dynamics of animal-to-human mutation transmission for influenza viruses. AB - g-FLUA2H is a web-based application focused on the analysis of the dynamics of influenza virus animal-to-human (A2H) mutation transmissions. The application only requires the viral protein sequences from both the animal and human host populations as input datasets. The comparative analyses between the co-aligned sequences of the two viral populations is based on a sliding window approach of size nine for statistical significance and data application to the major histocompatibility complex (MHC) and T-cell receptor (TCR) immune response mechanisms. The sequences at each of the aligned overlapping nonamer positions for the respective virus hosts are classified as four patterns of characteristic diversity motifs, as a basis for quantitative analyses: (i) "index", the most prevalent sequence; (ii) "major" variant, the second most common sequence and the single most prevalent variant of the index, with at least one amino acid mutation; (iii) "minor" variants, multiple different sequences, each with an incidence (percent occurrence) less than that of the major variant; and (iv) "unique" variants, each with only one occurrence in the alignment. The diversity motifs and their incidences at each of the nonamer positions allow evaluation of the mutation transmission dynamics and selectivity of the viral sequences in relation to the animal and the human hosts. g-FLUA2H is facilitated by a grid back-end for parallel processing of large sequence datasets. The web-application is publicly available at http://bioinfo.perdanauniversity.edu.my/g-FLUA2H. It can be used for a detailed characterization of the composition and incidence of mutations present in the proteomes of influenza viruses from animal and human host populations, for a better understanding of host tropism. PMID- 26680741 TI - Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins. AB - Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4 IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation. In contrast, increasing the levels of SPRY4-IT1 in the intestinal mucosa protected the gut barrier in mice exposed to septic stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted with TJ mRNAs, and this process was enhanced through the association with the RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These findings highlight a novel role for SPRY4-IT1 in controlling the intestinal epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ expression by altering the stability and translation of TJ mRNAs. PMID- 26680745 TI - Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium. AB - Metformin, a synthetic dimethyl biguanide, has been in clinical use for over 55 years, and today is considered the first-choice drug for the treatment of type 2 diabetes used by an estimated 125 million people worldwide. Metformin is orally effective, not metabolized, excreted unchanged by the kidney, relatively free of side effects and well tolerated by the majority of patients. Of importance is that the United Kingdom Prospective Diabetes Study 20-year study of type 2 diabetics, completed in 1998, compared patients treated with insulin, sulfonylureas and metformin and concluded that metformin provided vascular protective actions. Cardiovascular disease is the primary basis for the high morbidity and mortality that is associated with diabetes and that metformin proved to be protective resulted in a dramatic increase in its use. The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue. As reflected by a number of clinical studies, patients treated with metformin also have improvement in endothelial function as measured by the use of plethysmography and measurement of flow-mediated vasodilatation. These data as well as data from animal studies are supportive that metformin has a direct protective action on the vascular endothelium. In this review article, we discuss the pharmacology of metformin and critique the literature as to its cellular sites and mechanism(s) of action. PMID- 26680744 TI - Evaluation of a Web-Based Food Record for Children Using Direct Unobtrusive Lunch Observations: A Validation Study. AB - BACKGROUND: High-quality, Web-based dietary assessment tools for children are needed to reduce cost and improve user-friendliness when studying children's dietary practices. OBJECTIVE: To evaluate the first Web-based dietary assessment tool for children in Norway, the Web-based Food Record (WebFR), by comparing children's true school lunch intake with recordings in the WebFR, using direct unobtrusive observation as the reference method. METHODS: A total of 117 children, 8-9 years, from Baerum, Norway, were recruited from September to December 2013. Children completed 4 days of recordings in the WebFR, with parental assistance, and were observed during school lunch in the same period by 3 observers. Interobserver reliability assessments were satisfactory. Match, omission, and intrusion rates were calculated to assess the quality of the recordings in the WebFR for different food categories, and for all foods combined. Logistic regression analyses were used to investigate whether body mass index (BMI), parental educational level, parental ethnicity or family structure were associated with having a "low match rate" (<=70%). RESULTS: Bread and milk were recorded with less bias than spreads, fruits, and vegetables. Mean (SD) for match, omission, and intrusion rates for all foods combined were 73% (27%), 27% (27%), and 19% (26%), respectively. Match rates were statistically significantly associated with parental educational level (low education 52% [32%] versus high 77% [24%], P=.008) and parental ethnicity (non-Norwegian 57% [28%] versus others 75% [26%], P=.04). Only parental ethnicity remained statistically significant in the logistic regression model, showing an adjusted odds ratio of 6.9 and a 95% confidence interval between 1.3 and 36.4. CONCLUSIONS: Compared with other similar studies, our results indicate that the WebFR is in line with, or better than most of other similar tools, yet enhancements could further improve the WebFR. PMID- 26680746 TI - An integrative approach for efficient analysis of whole genome bisulfite sequencing data. AB - BACKGROUND: Whole genome bisulfite sequencing (WGBS) is a high-throughput technique for profiling genome-wide DNA methylation at single nucleotide resolution. However, the applications of WGBS are limited by low accuracy resulting from bisulfite-induced damage on DNA fragments. Although many computer programs have been developed for accurate detecting, most of the programs have barely succeeded in improving either quantity or quality of the methylation results. To improve both, we attempted to develop a novel integration of most widely used bisulfite-read mappers: Bismark, BSMAP, and BS-seeker2. RESULTS: A comprehensive analysis of the three mappers revealed that the mapping results of the mappers were mutually complementary under diverse read conditions. Therefore, we sought to integrate the characteristics of the mappers by scoring them to gain robustness against artifacts. As a result, the integration significantly increased detection accuracy compared with the individual mappers. In addition, the amount of detected cytosine was higher than that by Bismark. Furthermore, the integration successfully reduced the fluctuation of detection accuracy induced by read conditions. We applied the integration to real WGBS samples and succeeded in classifying the samples according to the originated tissues by both CpG and CpH methylation patterns. CONCLUSIONS: In this study, we improved both quality and quantity of methylation results from WGBS data by integrating the mapping results of three bisulfite-read mappers. Also, we succeeded in combining and comparing WGBS samples by reducing the effects of read heterogeneity on methylation detection. This study contributes to DNA methylation researches by improving efficiency of methylation detection from WGBS data and facilitating the comprehensive analysis of public WGBS data. PMID- 26680747 TI - Comparative magnitude and kinetics of human cytomegalovirus-specific CD4+ and CD8+ T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: Its utility for dating primary infection in pregnancy. AB - To discriminate between primary (PI) and remote (RI) human cytomegalovirus (HCMV) infection, several immunological parameters were monitored for a 2-year period in 53 pregnant women with PI, and 33 pregnant women experiencing HCMV PI at least 5 years prior. Cytokine (IFN-gamma and IL-2) production by and phenotype (effector/memory CD45RA(+)) of HCMV-specific CD4(+) and CD8(+) T-cells as well as the lymphoproliferative responses (LPR) were evaluated, with special reference to the comparison between a group of women transmitting (T) and a group of non transmitting (NT) the infection to fetus. While HCMV-specific CD4(+) T-cells reached at 90 days post-infection (p.i.) values comparable to RI, CD8(+) T-cells reached at 60 days p.i. levels significantly higher and persisting throughout the entire follow-up. Instead, IL-2 production and lymphoproliferative responses were lower in PI than RI for the entire follow-up period. Effector memory CD45RA(+) CD4(+) and CD8(+) HCMV-specific T-cells increased until 90 days p.i., reaching and maintaining levels higher than RI. The comparison between T and NT women showed that, at 30 days p.i., in NT women there was a significantly higher IL-2 production by HCMV-specific CD4(+) T-cells, and at 60 days p.i. a significantly higher frequency of both specific CD4(+) and CD8(+) CD45RA(+) T-cells. HCMV T cell response appears to correlate with virus transmission to fetus and some parameters (CD4(+) lymphoproliferation, and frequency of HCMV-specific CD8(+) IL2(+) T-cells) may help in dating PI during pregnancy. PMID- 26680748 TI - Translating Innovations to Success. PMID- 26680749 TI - Cytokeratin Expression at Different Stages in Sweat Gland Development of C57BL/6J Mice. AB - Sweat glands exhibit a documented role in epidermal reepithelialization after wounding. However, the regenerative potential of sweat glands has remained underappreciated due to the absence of useful markers for the analysis of determination and differentiation processes in the developing eccrine sweat gland from epithelium. Although the current knowledge of keratin expression in most of the different origins has been described, it remains widely shared and not unified in eccrine sweat glands of C57BL/6J mice that are commonly used as animal models for sweat gland and wound healing studies, both at the molecular and cellular levels. Aiming to answer this question, we have investigated the changes in cytokeratin expression patterns during the embryonic, neonatal, juvenile, and young adult stages (E12.5, E17.5, P0.5, P5, and P28). In this article, we demonstrate that the morphology of murine sweat gland progenitor cells are similar to epidermal stem cells before birth (E12.5 and E17.5); at postnatal stages, the duct formed gradually and curled to glob. K8 and K19 were expressed in the eccrine sweat gland cells at all times and highly expressed after birth at both gene and protein levels. Also, histological results revealed K8 and K19 positive cells localized in the secretary portion of glands. Meanwhile, K14 strongly expressed both in vivo and in vitro at E12.5, while it weakly expressed at other stages. Moreover, K10 was rarely detected before birth, but it expressed positively in vivo and in vitro only at the protein level after birth. These data indicate the pattern of main cytokeratin expression at different stages during murine sweat gland development and might provide an efficient tool for sweat gland research and exciting potential for developing targeted therapies for wound healing. PMID- 26680750 TI - Modern Orthopedic Inpatient Care of the Orthopedic Patient With Diabetic Foot Disease. AB - In this article, we describe emergency and elective pathways within our orthopedic multidisciplinary inpatient care of patients with diabetic foot problems. We performed a retrospective cohort review of 19 complex patients requiring orthopedic surgical treatment of infected ulceration or Charcot feet or deformity at our institution. A total of 30 admissions (19 emergency, 11 elective) were included. The pathways were coordinated by a multidisciplinary team and comprised initial assessment and investigation and a series of key events, which consisted of emergency and elective surgery together with the introduction, and change of intravenous antibiotics when indicated. Patients had rigorous microbiological assessment, in the form of deep ulcer swabs, operative tissue specimens, joint aspirates, and blood cultures according to their clinical presentation as well as close clinical and biochemical surveillance, which expedited the prompt institution of key events. Outcomes were assessed using amputation rates and patient satisfaction. In the emergency group, there were 5.6 +/- 3.0 (mean +/- SD) key events per admission, including 4.2 +/- 2.1 antibiotic changes. In the elective group, there were 4.8 +/- 1.4 key events per inpatient episode, with 3.7 +/- 1.3 antibiotic changes. Overall, there were 3 minor amputations, and no major amputations. The podiatric and surgical tissue specimens showed a wide array of Gram-positive, Gram-negative, aerobic and anaerobic isolates and 15% of blood cultures showed bacteremia. When 9 podiatric specimens were compared with 9 contemporaneous surgical samples, there was concordance in 2 out of 9 pairs. We have described the successful modern care of the orthopedic diabetic foot patient, which involves close clinical, microbiological, and biochemical surveillance by the multidisciplinary team directing patients through emergency and elective pathways. This has enabled successful surgical intervention involving debridement, pressure relief, and stabilization, with low rates of amputation. PMID- 26680751 TI - Severe Cardiac Autonomic Derangement and Altered Ventricular Repolarization Pave the Way to Postoperative Atrial Fibrillation. AB - OBJECTIVE: Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery. It has been shown that cardiac autonomic derangement plays a significant role in the genesis of atrial fibrillation (AF) and that AF might also be promoted by altered repolarization. Thus, the aim of our study was to determine the levels of cardiac autonomic modulation and repolarization properties in patients developing POAF. METHODS: Seventy-nine patients scheduled for aortic and/or coronary artery bypass grafting surgery with cardiopulmonary bypass were enrolled prospectively. High-resolution 20-minute electrocardiogram recordings were obtained day before surgery to determine P, PR, QT, and QTc intervals, as well as linear (time and frequency domain) and nonlinear heart rate variability parameters (fractal dimension and detrended fluctuation analysis). QTc interval was calculated using Framingham correction. RESULTS: Twenty-nine patients developed POAF (AF group), and 50 did not (non-AF group). Groups were similar regarding demographics, surgery type, and perioperative characteristics, except for older age in the AF group. QT and QTc intervals (Framingham) were longer in the AF group [442 (44) vs 422 (28) milliseconds, P = 0.018; and 448 (44) vs 431 (24) milliseconds, P = 0.031 and P = 0.019, respectively]. Time domain heart rate variability parameter PNN50 (percentage of pairs of adjacent NN intervals differing >50 milliseconds) was higher [14% (21%) vs 8% (16%), P = 0.015], and nonlinear parameter detrended fluctuation analysis alpha2 was lower in the AF group [0.81 (0.21) vs 0.91 (0.20), P = 0.031]. CONCLUSIONS: Profound cardiac autonomic derangement, suggestive of parasympathetic excessive modulation, exists preoperatively in patients inclined to POAF after cardiac surgery, whereby parameters PNN50 and alpha2 differentiated the AF from the non AF group. Prolonged QTc intervals are associated with an increased risk of POAF. PMID- 26680752 TI - Validation of a Novel Virtual Reality Training Curriculum for Robotic Cardiac Surgery: A Randomized Trial. AB - OBJECTIVE: Robotic cardiac surgery training has relied entirely on classical methods of surgical teaching. We sought to evaluate the impact of a virtual reality (VR) simulation curriculum to improve skill acquisition in robotic cardiac surgery. METHODS: We randomly assigned 20 surgical trainees to undergo a 9-exercise VR curriculum on a robotic surgical simulator or a control group that received no additional training. The trainees were then evaluated in a blinded fashion by assessing their de-identified video recordings of the following: (1) standardized robotic internal thoracic artery harvest and (2) mitral valve annuloplasty performed in porcine models, using a validated time-based scoring system and an objective intraoperative scoring tool. Postintervention assessments were compared to baseline. RESULTS: Trainees randomized to the VR group were faster than the control group for both the internal thoracic artery harvest (957.3 +/- 98.9 vs. 749.1 +/- 171.9; P = 0.004) and mitral annuloplasty (580.4 +/ 14.4 vs. 463.8 +/- 86.4; P < 0.001) and scored significantly higher with the intraoperative scoring tool (22.8 +/- 2.7 vs. 11.0 +/- 4.5; P < 0.001). Additionally, the VR group achieved a proficiency level similar to our experts for both time-based scores (P = 0.624 and P = 0.967), and the intraoperative assessment (P = 0.110), whereas the control group was not able to meet this level of proficiency for any of the primary outcomes. The average duration of training to successfully complete all required tasks was 9.3 hours. CONCLUSIONS: We have demonstrated that a VR simulation curriculum can significantly improve the efficiency and quality of learning in robotic cardiac surgery. Further evaluation of this curriculum is required for its widespread implementation in surgical training (ClinicalTrials.gov, NCT#02357056). PMID- 26680753 TI - Operative Strategies and Outcomes in Type A Aortic Dissection After the Enactment of a Multidisciplinary Aortic Surgery Team. AB - OBJECTIVE: The purpose of this study was to compare operative strategies and patient outcomes in acute type A aortic dissection (ATAAD) repairs before and after the implementation of a multidisciplinary aortic surgery team. METHODS: Between May 2005 and July 2014, 101 patients underwent ATAAD repair at our institution. A dedicated multidisciplinary aortic surgery team (experienced aortic surgeon, perfusionists, cardiac anesthesiologists, nurses, and radiologists) was formed in 2010. We retrospectively compared ATAAD repair outcomes in patients before (2005-2009, N = 39) and after (2010-2014, N = 62) implementation of our program. Expected operative mortality was calculated using the International Registry of Acute Aortic Dissection preoperative predictive model. RESULTS: This study demonstrated a significant reduction in operative mortality after implementation of the aortic surgery program (30.8% vs. 9.7%; P = 0.014). There was also an increase in the complexity of surgical technique and perfusion strategies with fewer postoperative complications related to respiratory (P < 0.0001) and renal failure (P = 0.034). Baseline demographics were similar, and there was no statistically significant difference in International Registry of Acute Aortic Dissection predictive variables between the 2 groups. However, there was a 3.5-fold reduction in the observed-to-expected (O/E) operative mortality ratio. There was a 50% increase in volume with a significant number of patients being admitted directly to our aortic center for ATAAD repair, thus avoiding delay in operation related to transfers from a secondary hospital. CONCLUSIONS: Patient outcomes are improved when the surgical treatment of ATAAD is managed by a high-volume multidisciplinary aortic surgery team. PMID- 26680754 TI - Total Arterial Minimally Invasive Direct Coronary Artery Bypass Surgery Facilitated by the Trinity Clip Connector. AB - OBJECTIVE: This pilot study evaluated the feasibility of total arterial minimally invasive direct coronary artery bypass surgery by using the Trinity Clip anastomotic connector in an acute porcine model. METHODS: In 3 pigs, the left and right internal thoracic arteries (LITA and RITA) were harvested conventionally and the chest closed subsequently. After a left lateral thoracotomy, the coronary target was positioned and stabilized by an endo-starfish and octopus. A free RITA to-LITA y-graft, with a LITA-to-left anterior descending coronary artery (LAD) and a free RITA-to-obtuse marginal or posterolateral or posterior descending artery, was constructed using the Trinity Clip. Patency was assessed with angiography (n = 3 anastomoses). RESULTS: The anastomotic procedure was feasible via a small lateral thoracotomy, with a fast construction of the y-graft, and successful application of the mounted complex (ie, graft, connector, and laser, temporarily fixated by a fixation clip) onto the LAD. Access to the obtuse marginal artery, posterolateral artery, and posterior descending artery was possible, with successful construction, resulting in patent anastomoses. CONCLUSIONS: This experimental pilot study demonstrates the feasibility of the anastomotic technique in a total arterial minimally invasive direct coronary artery bypass approach. Revascularization of the anterior, lateral, and inferoposterior regions of the heart is possible. However, visibility during the introduction of the connector was limited, and videoscopic assistance is essential to allow for successful construction. The anastomotic technique has potential to facilitate minimally invasive coronary bypass surgery. PMID- 26680755 TI - A teaching skills assessment tool inspired by the Calgary-Cambridge model and the patient-centered approach. AB - OBJECTIVE: The aim of this study was to develop a descriptive tool for peer review of clinical teaching skills. Two analogies framed our research: (1) between the patient-centered and the learner-centered approach; (2) between the structures of clinical encounters (Calgary-Cambridge communication model) and teaching sessions. METHOD: During the course of one year, each step of the action research was carried out in collaboration with twelve clinical teachers from an outpatient general internal medicine clinic and with three experts in medical education. The content validation consisted of a literature review, expert opinion and the participatory research process. Interrater reliability was evaluated by three clinical teachers coding thirty audiotaped standardized learner-teacher interactions. RESULTS: This tool contains sixteen items covering the process and content of clinical supervisions. Descriptors define the expected teaching behaviors for three levels of competence. Interrater reliability was significant for eleven items (Kendall's coefficient p<0.05). CONCLUSION: This peer assessment tool has high reliability and can be used to facilitate the acquisition of teaching skills. PMID- 26680756 TI - Barriers to communication between HIV care providers (HCPs) and women living with HIV about child bearing: A qualitative study. AB - OBJECTIVES: In the context of HIV clinical care, open discussion regarding sexual health and reproductive plans has become increasingly relevant. The aim of this paper is to explore barriers to communication between providers and women living with HIV regarding childbearing. METHODS: In-depth interviews (IDIs) were conducted with 48 HIV infected women receiving ART at 7 different HIV clinics providing comprehensive HIV care services in four districts in Uganda, between July and August 2012. All women were aware of their HIV diagnosis prior to pregnancy or had given birth while living with HIV. RESULTS: Four themes emerged describing barriers to communication, from the HIV-positive women's point of view: (i) provider indifference or opposition to childbearing post HIV diagnosis, (ii) anticipation of negative response from provider, (iii) provider's emphasis on 'scientific' facts, (iv) 'accidental pregnancy'. CONCLUSION: Existing evidence regarding effective provider-patient communication should be considered for its application for reproductive counseling among HIV infected women. PRACTICE IMPLICATIONS: These data demonstrate the need for current counseling guidelines to explore approaches that encourage open, non-judgmental, non-directive discussions with HIV positive individuals around their reproductive desires and intentions in a health care setting. PMID- 26680757 TI - Women's experiences after Planned Parenthood's exclusion from a family planning program in Texas. AB - OBJECTIVE: We assessed the impact on depot medroxyprogesterone continuation when a large care provider was banned from a state-funded family planning program. STUDY DESIGN: We used three methods to assess the effect of the ban: (a) In a records review, we compared how many state program participants returned to two Planned Parenthood affiliates for a scheduled dose of depot medroxyprogesterone acetate (DMPA) immediately after the ban; (b) We conducted phone interviews with 224 former Planned Parenthood patients about DMPA use and access to contraception immediately after the ban; (c) We compared current contraceptive method of our interviewees to that of comparable DMPA users in the National Survey of Family Growth 2006-2010 (NSFG). RESULTS: (a) Fewer program clients returned for DMPA at a large urban Planned Parenthood, compared to a remotely located affiliate (14.4%, vs. 64.8%), reflecting different levels of access to alternative providers in the two cities. (b) Among program participants who went elsewhere for the injection, only 56.8% obtained it at no cost and on time. More than one in five women missed a dose because of barriers, most commonly due to difficulty finding a provider. (c) Compared to NSFG participants, our interviewees used less effective methods of contraception, even more than a year after the ban went into effect. CONCLUSIONS: Injectable contraception use was disrupted during the rollout of the state-funded family planning program. Women living in a remote area of Texas encountered more barriers. IMPLICATIONS: Requiring low-income family planning patients to switch healthcare providers has adverse consequences. PMID- 26680758 TI - Discontinuation rates and acceptability during 1 year of using the intrauterine ball (the SCu380A). AB - OBJECTIVE: To characterize method-related discontinuation rates and acceptability over 1 year of SCu380A use. STUDY DESIGN: Women enrolled into this prospective pilot study underwent SCu380A placement by a single clinician with follow-up at 6 8 weeks and at 3, 6, 9 and 12 months. Outcome measures included reasons for discontinuation and satisfaction. RESULTS: Fifty-one women had a 12-mm-diameter intrauterine ball (IUB; SCu380A) inserted by a single clinician (EW). Postinsertion ultrasonography showed all the devices to be correctly placed. By 8 weeks, there were 9 expulsions and 2 removals for symptoms. By 12 months, there were 14 expulsions (27%), 8 removals for symptoms (16%), 1 pregnancy and 7 lost to follow-up. Of the remaining 21 women, 15 said that they were satisfied. CONCLUSION: The high rate of expulsions and removals for symptoms in the first year indicates that this device, as presently designed, is unacceptable as an alternative to the currently available copper intrauterine devices. IMPLICATIONS: More research is needed before we know if it is the spherical design, the size of the device or some other factor that led to the high expulsion rate. There are currently three different IUBs (12, 15 and 18 mm) approved and being investigated. PMID- 26680759 TI - Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases. AB - BACKGROUND: Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. CASE PRESENTATION: The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. CONCLUSION: These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause. PMID- 26680760 TI - Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs. AB - There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybridization (ISH) markers to porcine eyes. In this study, OCT and OCT angiography (AngioOCT) were performed on adult Gottingen minipigs. To increase structural information on retinal and choroidal vasculature, OCT data were speckle denoized and choroidal blood vessels were segmented with threshold filtering. In addition, we established a set of IHC and ISH markers on Davidson's fixed paraffin-embedded minipig eyes: neurofilament-160, neuronal nuclei, calretinin, protein kinase C-alpha, vimentin, glial fibrillary acidic protein, glutamine synthetase, ionized calcium-binding adaptor molecule-1, rhodopsin, synaptophysin, postsynaptic density protein-95, retinal pigment epithelium (RPE) specific protein-65, von Willebrand factor, alpha-smooth muscle actin, desmin, and Ki-67, thus enabling visualization of retinal neuronal and glial cells, photoreceptors, synapses, RPE, blood vessels, myocytes, macrophages, or cell proliferation. Using ISH, transcripts of vascular endothelial growth factor A, angiopoietin-2, and endothelial tyrosine kinase were visualized. This article describes for the first time in minipig eyes speckle noise-free OCT, AngioOCT, and a set of IHC/ISH markers on Davidson's fixed paraffin-embedded tissues and helps to establish the minipig for ocular toxicology and pharmacology studies. PMID- 26680763 TI - Molecular Cytogenetics in Digenean Parasites: Linked and Unlinked Major and 5S rDNAs, B Chromosomes and Karyotype Diversification. AB - Digenetic trematodes are the largest group of internal metazoan parasites, but their chromosomes are poorly studied. Although chromosome numbers and/or karyotypes are known for about 300 of the 18,000 described species, molecular cytogenetic knowledge is mostly limited to the mapping of telomeric sequences and/or of major rDNA clusters in 9 species. In this work we mapped major and 5S rDNA clusters and telomeric sequences in chromosomes of Bucephalus minimus, B. australis, Prosorhynchoides carvajali (Bucephaloidea), Monascus filiformis (Gymnophalloidea), Parorchis acanthus (Echinostomatoidea), Cryptocotyle lingua (Opisthorchioidea), Cercaria longicaudata, Monorchis parvus (Monorchioidea), Diphterostomum brusinae, and Bacciger bacciger (Microphalloidea). Whilst single major and minor rDNA clusters were mapped to different chromosome pairs in B. minimus and P. acanthus, overlapping signals were detected on a single chromosome pair in the remaining taxa. FISH experiments using major rDNA and telomeric probes clearly demonstrated the presence of highly stretched NORs in most of the digenean taxa analyzed. B chromosomes were detected in the B. bacciger samples hosted by Ruditapes decussatus. Although the cercariae specimens obtained from Donax trunculus, Tellina tenuis, and R. decussatus were in agreement with B. bacciger, their karyotypes showed striking morphological differences in agreement with the proposed assignation of these cercariae to different species of the genus Bacciger. Results are discussed in comparison with previous data on digenean chromosomes. PMID- 26680762 TI - Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy. AB - The epileptic network is characterized by pathologic, seizure-generating 'foci' embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci-a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices. PMID- 26680764 TI - Stepped psychological care after stroke. AB - PURPOSE: Emotional difficulties are common after stroke and have an impact on rehabilitation outcome. It is a challenge to manage these problems effectively, particularly in times of resource stringency. One proposal for how to do this has arisen out of an approach to general mental health management: a system of 'stepped care'. Such a system directs intervention by considering level of need, thereby making the most efficient use of available resources. It is the purpose of this article to articulate a stepped psychological care approach for emotional problems after stroke. METHOD: Narrative review and elaboration of the model proposed by the Department of Health in England for the management of emotional problems after stroke. RESULTS: A stepped care model for the management of emotional problems after stroke is presented in detail, including descriptions of specific interventions and guidance to inform the level of management. CONCLUSIONS: The stepped psychological care proposal for emotional problems after stroke requires evaluation but is potentially of use within comparable healthcare systems. Implications for Rehabilitation Emotional problems are common after stroke and effect rehabilitation outcomes. A stepped care approach to these problems offers the ability to cater to all according to need. Greater specification of the services at each step can be outlined. While recommended, such an approach requires evaluation to prove its efficacy. PMID- 26680766 TI - Patchy sediment contamination scenario and the habitat selection by an estuarine mudsnail. AB - Since mudsnails are able to avoid contaminated sediment and that the contaminants in sediment are not uniformly distributed, the mudsnail Peringia ulvae was exposed to cadmium (Cd) spiked sediment and assessed for avoidance response in a heterogeneous contamination scenario. Four Cd concentrations were prepared and disposed in patches on dishes, which were divided in 25 fields (six fields for each sediment concentration); 24 organisms were deployed in the central field, with no sediment. Observations were made at 2, 4 and 6 h (corresponding to immediate response), 8, 10 and 12 h (very short term), and 24 h (short term). A trend to avoid contaminated patches was observed in the immediate and very short term. After 24 h exposure, the organisms exposed to the highest level of contamination seemed to have lost the ability to move and avoid contaminated patches. In a contamination scenario in which non- and contaminated sediment patches are heterogeneously distributed, local mudsnail populations can simply rearrange their locality without needing to move to a different habitat. Such less contaminated patches can become donor areas in a future recolonization scenario. PMID- 26680765 TI - Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk. AB - A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup's growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation. PMID- 26680767 TI - Atorvastatin improves pathological changes in the aged kidney by upregulating peroxisome proliferator-activated receptor expression and reducing matrix metalloproteinase-9 and transforming growth factor-beta1 levels. AB - OBJECTIVE: To investigate the effects of atorvastatin (AVT) on renal function and renal pathological changes in the aged rat and explore their possible mechanisms. METHODS: Twenty-month-old, normal female Wistar rats were divided into three groups: group A (n=8) was fed high-dose AVT (10mg/kg/d); group B (n=8) was fed low-dose AVT (1mg/kg/d); and group C (controls, n=8) received the same volume of normal saline; 3-month-old, normal female Wistar rats served as young normal controls (n=8). All rats were sacrificed following a 4-month treatment period. Serum creatinine and blood lipid levels were measured. The glomerular sclerosis index and tubulointerstitial lesions were determined using renal periodic acid Schiff-stained paraffin sections. The mRNA and protein expressions of matrix metalloproteinases (MMP)-9 and -2, tissue inhibitors of metalloproteinase (TIMP) 1 and -2, transforming growth factor-beta1 (TGF-beta1), and peroxisome proliferator-activated receptors (PPARs) were examined using reverse transcription polymerase chain reactions and Western blots, respectively. RESULTS: Serum lipid (including serum cholesterol and serum triglycerides) levels in aged rats were significantly higher than those in young rats (p<0.05). Compared to the aged control group, high-dose AVT was associated with significantly lower serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in aged rats (p<0.05); low-dose AVT was associated only with lower serum LDL-C levels (p<0.05). Renal morphological changes in aged rats included focal glomerulosclerosis, infiltration of inflammatory cells, and arteriole sclerosis. Improved renal pathology was observed in aged, AVT-treated rats, and included a decreased glomerular sclerosis index and tubulointerstitial lesion score, especially in those receiving high-dose AVT. Additionally, renal artery wall thickening, luminal narrowing, and arteriolosclerosis were significantly less severe in aged rats receiving high-dose AVT. Upregulated expression of MMP-9 and TGF-beta1 was observed in the renal tissue of aged rats. AVT treatment was associated with a reversal of these phenomena and upregulated expression of TIMP-1, PPARalpha, PPARbeta, and PPARgamma in aged rats. CONCLUSION: AVT improved the renal pathology of aged rats. These effects may have been induced by the lowering of blood lipids, maintaining the MMP/TIMP balance, and downregulating the expression of TGF-beta1. AVT may reduce the levels of MMP 9 and TGF-beta in aged rats by upregulating the expression of PPARs. PMID- 26680768 TI - Effects of alcohol intake on time-based event expectations. AB - Previous evidence suggests that alcohol affects various forms of temporal cognition. However, there are presently no studies investigating whether and how alcohol affects on time-based event expectations. Here, we investigated the effects of alcohol on time-based event expectations. Seventeen healthy volunteers, aged between 19 and 36 years, participated. We employed a variable foreperiod paradigm with temporally predictable events, mimicking a computer game. Error rate and reaction time were analyzed in placebo (0 g/kg), low dose (0.2 g/kg) and high dose (0.6 g/kg) conditions. We found that alcohol intake did not eliminate, but substantially reduced, the formation of time-based expectancy. This effect was stronger for high doses, than for low doses, of alcohol. As a result of our studies, we have evidence that alcohol intake impairs time-based event expectations. The mechanism by which the level of alcohol impairs time based event expectations needs to be clarified by future research. PMID- 26680769 TI - Grasping a 2D object: terminal haptic feedback supports an absolute visuo-haptic calibration. AB - Grasping a three-dimensional (3D) object results in the specification of motor output via absolute size information. In contrast, the impoverished visual cues (e.g., binocular and vergence) associated with grasping a two-dimensional (2D) object are reported to render aperture formation via an object's perceptual and relative visual features. It is, however, important to recognize that 3D and 2D grasping differ not only in terms of their visual properties, but also because the latter does not entail the provision of haptic feedback. As such, the present work examined whether haptic feedback influences the nature of the information supporting 2D grasping. Participants grasped differently sized 3D objects (i.e., 3D task) and completed a 'traditional' 2D grasping task to line drawings without receiving haptic feedback (i.e., 2DH- task). As well, we included a separate condition using the same objects as the 2DH- task; however, the experimenter placed a 3D object (i.e., one corresponding to the size of the 2D object) between the thumb and forefinger of participants' grasping limb once they completed their response (i.e., 2DH+ task). Thus, the 2DH+ task provided haptic feedback related to absolute object size. Notably, we computed just-noticeable-difference (JND) scores to determine whether the different tasks adhered to, or violated, the relative psychophysical principles of Weber's law. JNDs for the 2DH- task adhered to Weber's law, whereas 3D and 2DH+ tasks violated the law. Thus, results evince that 2DH- and 2DH+ tasks are specified via relative and absolute object size information, respectively. Accordingly, we propose that haptic feedback supports an absolute visuo-haptic calibration and contend that our results highlight the importance of multi-sensory cue integration in goal-directed grasping. PMID- 26680770 TI - Sequential actions: effects of upcoming perceptual and motor tasks on current actions. AB - Reports of spatial interactions between current and upcoming elements in a movement sequence could be due to intentional planning of a "global" action sequence (i.e., strategic effects), or to unintentional motor planning arising from merely paying attention to upcoming target objects (i.e., interference effects). The purpose of this experiment was to determine whether paying attention to an upcoming target object could induce kinematic changes in a current grasping action when there is no strategic advantage associated with such changes. Specifically, participants grasped a rectangular target object in the presence of a second rectangular object that was either ignored, or was the target of a subsequent grasping or perceptual judgment task. Peak grip aperture during the primary grasping action was assessed in relation to the size of the second rectangle. The results revealed an effect of the second rectangle's size only when it was the target of a subsequent perceptual judgment task. This result calls into question the assumption that interactions between current and subsequent elements of an action sequence are necessarily due to strategic movement planning processes and might instead arise from interference arising from merely paying attention to nontarget objects. PMID- 26680771 TI - DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors. AB - DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 uM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray. A 7-day intervention sufficed to induce contractile dysfunction and significantly decrease promoter methylation of hypertrophy-associated upregulated genes such as Nppa (encoding ANP) and Acta1 (alpha-skeletal actin) in both intervention groups. To evaluate whether pathological consequences of AE are affected by inhibiting de novo DNA methylation we applied AE in the absence and presence of DNA methyltransferase (DNMT) inhibitors: 5-aza-2'-deoxycytidine (aza, 100 uM, nucleosidic inhibitor), RG108 (60 uM, non-nucleosidic) or methylene disalicylic acid (MDSA, 25 uM, non-nucleosidic). Aza had no effect on EHT function, but RG108 and MDSA partially prevented the detrimental consequences of AE on force, contraction and relaxation velocity. RG108 reduced AE-induced Atp2a2 (SERCA2a) promoter methylation. The results provide evidence for dynamic DNA methylation in cardiac hypertrophy and warrant further investigation of the potential of DNA methylation in the treatment of cardiac hypertrophy. PMID- 26680772 TI - Mechanisms Explaining the Influence of Subclinical Hypothyroidism on the Onset and Progression of Chronic Heart Failure. AB - BACKGROUND: Subclinical hypothyroidism can be associated with the onset and progression of chronic heart failure. METHODS: We undertook a careful search of the literature aiming to review the possible pathogenetic mechanisms explaining the influence of subclinical hypothyroidism on the onset and progression of chronic heart failure. RESULTS: Thyroid hormones can influence the expression of genes involved in calcium handling and contractile properties of myocardiocytes. Subclinical hypothyroidism, therefore, can alter both cardiovascular morphology and function leading to changes in myocardiocytes shape and structure, and to alterations of both contractile and relaxing properties, impairing systolic as well as diastolic functions. Furthermore, it can favour dyslipidemia, endothelial dysfunction and diastolic hypertension, favouring atherogenesis and coronary heart disease, possibly evolving into chronic heart failure. Beside an influence on the onset of chronic heart failure, subclinical hypothyroidism can represent a risk factor for its progression, in particular hospitalization and mortality but the mechanisms involved need to be fully elucidated. CONCLUSIONS: Subclinical hypothyroidism can be associated with the onset of chronic heart failure, because it can favour two frequent conditions that can evolve in heart failure: coronary heart disease and hypertension; it can also alter both cardiovascular morphology and function leading to heart failure progression in patients already affected through mechanisms still not completely understood. PMID- 26680773 TI - Cerebral Hypoperfusion in Hereditary Coproporphyria (HCP): A Single Photon Emission Computed Tomography (SPECT) Study. AB - BACKGROUND: Hereditary Coproporphyria (HCP) is characterized by abdominal pain, neurologic symptoms and psychiatric disorders, even if it might remain asymptomatic. The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. Therefore, aiming to evaluate a possible role of brain blood flow disorders, we have retrospectively investigated cerebral perfusion patterns in Single Photon Emission Computed Tomography (SPECT) studies in HCP patients. MATERIALS & METHODS: We retrospectively evaluated the medical records of patients diagnosed as being affected by HCP. A total of seven HCP patients had been submitted to brain perfusion SPECT study with 99mTc-Exametazime (hexamethylpropyleneamine oxime, HMPAO) or with its functionally equivalent 99mTc Bicisate (ECD or Neurolite) according with common procedures. In 3 patients the scintigraphic study had been repeated for a second time after the first evaluation at 3, 10 and 20 months, respectively. All the studied subjects had been also submitted to an electromyographic and a Magnetic Resonance Imaging (MRI) study of the brain. RESULTS: Mild to moderate perfusion defects were detected in temporal lobes (all 7 patients), frontal lobes (6 patients) and parietal lobes (4 patients). Occipital lobe, basal ganglia and cerebellar involvement were never observed. In the three subjects in which SPECT study was repeated, some recovery of hypo-perfused areas and appearance of new perfusion defects in other brain regions have been found. In all patients electromyography resulted normal and MRI detected few unspecific gliotic lesions only in one patient. Discussion & Conclusions: Since perfusion abnormalities were usually mild to moderate, this can probably explain the normal pattern observed at MRI studies. Compared to MRI, SPECT with 99mTc showed higher sensitivity in HCP patients. Changes observed in HCP patients who had more than one study suggest that transient perfusion defects might be due to a brain artery spasm possibly leading to psychiatric and neurologic symptomatology, as already observed in patients affected by acute intermittent porphyria. This observation, if confirmed by other well designed studies aiming to demonstrate a direct link between artery spasm, perfusion defects and related symptoms could lead to improvements in HCP treatments. PMID- 26680774 TI - Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing. AB - BACKGROUND: Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. MATERIALS/METHODS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. RESULTS: European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. CONCLUSIONS: Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry--and the inverse for European ancestry--were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality. PMID- 26680776 TI - Scientists take first steps to form united front over interactions with global food industry. PMID- 26680775 TI - Association of environmental chemicals & estrogen metabolites in children. AB - BACKGROUND: The prevalence of pediatric hormonal disorders and hormonally sensitive cancers are rising. Chemicals including bisphenol A (BPA), phthalates, parabens, 4-nonylphenol (4NP) and triclosan have been linked to disruption of endocrine pathways and altered hormonal status in both animal and human studies. Additionally, changes in estrogen metabolism have been associated with pediatric endocrine disorders and linked to estrogen-dependent cancers. The main objective of the study was to measure the presence of these environmental chemicals in prepubescent children and assess the relationship between chemical metabolites and estrogen metabolism. METHODS: 50 subjects (25 male, 25 female) were recruited from the principal investigator's existing patient population at his pediatric primary care office. The first 5 boys and 5 girls in each age group (4 through 8 years old inclusive) who presented for annual examinations were included, as long as they were Tanner Stage I (prepubertal) on physical exam, without diagnosis of hormonally-related condition and/or cancer and able to give a urine sample. Urine samples were collected in glass containers for analysis of chemical and estrogen metabolites. Study kits and lab analysis were provided by Genova Diagnostics (Duluth, GA). Summary statistics for the concentrations of each chemical metabolite as well as estrogen metabolites were computed (minimum, maximum, median and inter-quartile range) for males only, for females only and for all subjects. Comparisons between groups (e.g. males v. females) were assessed using the nonparametric Wilcoxon test, since the data was skewed. The correlation between concentrations of chemical metabolites and estrogen metabolites in prepubescent children were examined by the Spearman's correlation coefficient (rho). RESULTS: 100 % of subjects had detectable levels of at least five chemicals [corrected] in their urine, and 74 % had detectable levels of eight or more chemicals. 28 % of subjects had measurable levels of 4NP. No associations were found between the urine levels of chemicals and estrogen metabolites. CONCLUSIONS: Endocrine disrupting environmental chemicals were detected in all children in the study, with measurable levels of 4NP in nearly 1/3 of subjects. This is the first known published study of 4NP levels in American children. No associations were found between the urine levels of chemicals tested and estrogen metabolites. The presence of multiple chemicals in a majority of children's urine coupled with increasing prevalence of pediatric hormonal disorders warrants further research to elucidate potential causal mechanisms in pre- and post pubertal children. PMID- 26680777 TI - Center of Pressure Displacement of Standing Posture during Rapid Movements Is Reorganised Due to Experimental Lower Extremity Muscle Pain. AB - BACKGROUND: Postural control during rapid movements may be impaired due to musculoskeletal pain. The purpose of this study was to investigate the effect of experimental knee-related muscle pain on the center of pressure (CoP) displacement in a reaction time task condition. METHODS: Nine healthy males performed two reaction time tasks (dominant side shoulder flexion and bilateral heel lift) before, during, and after experimental pain induced in the dominant side vastus medialis or the tibialis anterior muscles by hypertonic saline injections. The CoP displacement was extracted from the ipsilateral and contralateral side by two force plates and the net CoP displacement was calculated. RESULTS: Compared with non-painful sessions, tibialis anterior muscle pain during the peak and peak-to-peak displacement for the CoP during anticipatory postural adjustments (APAs) of the shoulder task reduced the peak-to peak displacement of the net CoP in the medial-lateral direction (P<0.05). Tibialis anterior and vastus medialis muscle pain during shoulder flexion task reduced the anterior-posterior peak-to-peak displacement in the ipsilateral side (P<0.05). CONCLUSIONS: The central nervous system in healthy individuals was sufficiently robust in maintaining the APA characteristics during pain, although the displacement of net and ipsilateral CoP in the medial-lateral and anterior posterior directions during unilateral fast shoulder movement was altered. PMID- 26680779 TI - Postoperative delirium assessed by post anesthesia care unit staff utilizing the Nursing Delirium Screening Scale: a prospective observational study of 1000 patients in a single Swiss institution. AB - BACKGROUND: Delirium has become better studied, but is still only partially understood and significantly underestimated. There are some well-known risk factors, but little is known about the incidence of delirium in the diverse patient population of a post anesthesia care unit (PACU). The aim of this study was to investigate the presence of delirium using the Nursing Delirium Screening Scale (NU-DESC). METHODS: 1000 consecutive patients in the PACU were prospectively evaluated at the point when being ready to be transferred to the normal ward by the registered nurses of the PACU. RESULTS: The data of 1,000 patients was recorded. 242 of the patients (24.2%) were preoperatively classified as ASA I physical status, 664 patients (66.4%) as ASA II. A total of 43 patients (4.3%) presented with a delirium at the time point where they would have been transferred to the normal ward (138.4 +/- 55.2 min after arrival in the PACU). 287 patients (28.7%) of the entire group were over the age of 70 years. Considering only this subgroup, delirium was diagnosed in 30 individuals (10.5%). CONCLUSIONS: Delirium screening with the NU-DESC, collected by nursing staff of a PACU is easily feasible and demonstrated a low incidence of delirium in the presented setting. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien, www.drks.de ; DRKS 000005426 ; date of registration 4th December 2013). PMID- 26680778 TI - High residual platelet reactivity (HRPR) for adenosine diphosphate (ADP) stimuli is a determinant factor for long-term outcomes in acute ischemic stroke with anti platelet agents: The meaning of HRPR after ADP might be more prominent in large atherosclerotic infarction than other subtypes of AIS. AB - High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70 % or greater according to OPA after 10 uM ADP stimuli. The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3 % (109/968). Its rate was significantly higher in the patients with HRPR (16.7 %) than in those without (9.7 %). HPRP was independently associated with the primary endpoint (OR = 1.97, CI 1.22-3.18, p < 0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR = 2.26, CI 1.15-4.45, p = 0.02). In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS. PMID- 26680780 TI - Five-year evolution of reperfusion strategies and early mortality in patients with ST-segment elevation myocardial infarction in France. AB - AIM: To assess 5-year evolutions in reperfusion strategies and early mortality in patients with ST-segment elevation myocardial infarction. METHODS AND RESULTS: Using data from the French RESCUe network, we studied patients with ST-segment elevation myocardial infarction treated in mobile intensive care units between 2009 and 2013. Among 2418 patients (median age 62 years; 78.5% male), 2119 (87.6%) underwent primary percutaneous coronary intervention and 299 (12.4%) pre hospital thrombolysis (94.0% of whom went on to undergo percutaneous coronary intervention). Use of primary percutaneous coronary intervention increased from 78.4% in 2009 to 95.9% in 2013 ( Ptrend<0.001). Median delays included: first medical contact to percutaneous coronary intervention centre 48 minutes; first medical contact to balloon inflation 94 minutes; and percutaneous coronary intervention centre to balloon inflation 43 minutes. Times from symptom onset to first medical contact and first medical contact to thrombolysis remained stable during 2009-2013, but times from symptom onset to first balloon inflation, and first medical contact to percutaneous coronary intervention centre to first balloon inflation decreased ( P<0.001). Among patients with known timings, 2146 (89.2%) had a first medical contact to percutaneous coronary intervention centre delay ?90 minutes, while 260 (10.8%) had a longer delay, with no significant variation over time. Primary percutaneous coronary intervention use increased over time in both delay groups, but was consistently higher in the ?90 versus >90 minutes delay group (83.0% in 2009 to 97.7% in 2013; Ptrend<0.001 versus 34.1% in 2009 to 79.2% in 2013; Ptrend<0.001). In-hospital (4-6%) and 30-day (6-8%) mortalities remained stable from 2009 to 2013. CONCLUSION: In the RESCUe network, the use of primary percutaneous coronary intervention increased from 2009 to 2013, in line with guidelines, but there was no evolution in early mortality. PMID- 26680781 TI - Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes. AB - OBJECTIVES: To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections. METHODS: Retrospective review of adult patients with positive HSV or VZV polymerase chain reaction on CSF from an observational study of meningitis or encephalitis in Houston, TX (2004-2014), and New Orleans, LA (1999-2008). RESULTS: Ninety-eight adults patients were identified; 25 had encephalitis [20 (20.4 %) HSV, 5 (5.1 %) VZV], and 73 had meningitis [60 (61.1 %) HSV and 13 (13.3 %) VZV]. HSV and VZV had similar presentations except for nausea (P < 0.01) and rash (P < 0.001). The CSF profile did not differ between HSV and VZV infection. Abnormal neuroimaging findings were found in 11.6 % (10/86) brain CTs and 21.3 % (16/75) brain MRIs. The EEG was abnormal in 57.9 % (11/19). Sixteen patients (16.3 %) had an ACO (10 HSV encephalitis, 3 VZV encephalitis and 3 VZV meningitis). Intravenous acyclovir administered within 48 h was protective against an ACO [OR 0.19 (0.04-0.80), P = 0.02). However, on logistic regression only Charlson comorbidity score >1 and an encephalitis presentation were independently associated with an ACO. The treatment for HSV meningitis was variable, and all patients had a good clinical outcome. CONCLUSION: Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation. PMID- 26680783 TI - SPOTting Model Parameters Using a Ready-Made Python Package. AB - The choice for specific parameter estimation methods is often more dependent on its availability than its performance. We developed SPOTPY (Statistical Parameter Optimization Tool), an open source python package containing a comprehensive set of methods typically used to calibrate, analyze and optimize parameters for a wide range of ecological models. SPOTPY currently contains eight widely used algorithms, 11 objective functions, and can sample from eight parameter distributions. SPOTPY has a model-independent structure and can be run in parallel from the workstation to large computation clusters using the Message Passing Interface (MPI). We tested SPOTPY in five different case studies to parameterize the Rosenbrock, Griewank and Ackley functions, a one-dimensional physically based soil moisture routine, where we searched for parameters of the van Genuchten-Mualem function and a calibration of a biogeochemistry model with different objective functions. The case studies reveal that the implemented SPOTPY methods can be used for any model with just a minimal amount of code for maximal power of parameter optimization. They further show the benefit of having one package at hand that includes number of well performing parameter search methods, since not every case study can be solved sufficiently with every algorithm or every objective function. PMID- 26680782 TI - Actinobaculum schaalii, a new cause of knee prosthetic joint infection in elderly. AB - Actinobaculum schaalii is an emerging pathogen particularly involved in urinary tract infection of elderly people and/or patient with urological risk factors of urinary tract infection. This microorganism is a difficult-to-diagnose pathogen and is rarely involved in systemic or deep infections. Here, we report the first case of prosthetic joint infection due to A. schaalii in an 84-year-old man with a benign prostatic hyperplasia associated with chronic retention of urine. This case underlines the importance to optimize the diagnosis of emerging uropathogens as A. schaalii, to prevent systemic infections, particularly in patients with orthopaedic implants. PMID- 26680785 TI - A Study of the Survival Rate of Childhood Cancer in Korea. AB - PURPOSE: It is known that the prognosis of childhood cancer is relatively good, however actual representative nationwide data on childhood cancer, particularly of survival rate, are rare. In this study we attempted to establish the overall survival rate of major childhood cancer. MATERIALS AND METHODS: The primary source of data of childhood cancer under 15 years of age were the registry files of the Central Cancer Registry Report (Ministry of Health & Welfare) from 1993 to 1997. The above data was compared to death case data files of the same period obtained from the Korea National Statistical Office using the personal identification code. We calculated the 1, 3, and 5 year survival rates using the life table of SPSS and Kaplan-Meier method and compared the survival rate of disease according to prognostic factors. RESULTS: A total of 6,720 cases of pediatric cancer from the Central Cancer Registry files were computerized and sorted by personal identification (ID) code to extract duplicated cases as well as cases with incomplete data. The final number of cases entered in this study was 4,983. 1) The number of confirmed death cases was 1,448 (29.1%). 2) The disease distribution showed that the most common pediatric cancer was leukemia (1,468/4,983, 29%), followed by brain tumors (503/4,983, 10%), lymphoma (315/4,983, 6%), Wilms tumor (165/4,983, 3%), etc. in order by number of patients. 3) The 5 year survival rate of disease was as follows: overall 62%, acute lymphocytic leukemia 61%, acute non-lymphocytic leukemia 32%, malignant lymphoma 72%, neuroblastoma 47%, medulloblastoma 51%, Astrocytoma 66%, Wilms tumor 83%, etc. CONCLUSION: We analyzed and report the 5 year survival rate of overall childhood cancer and of each of the twelve major childhood cancers from in Korea 1993 to 1997 to provide basic data on childhood cancer statistics. PMID- 26680784 TI - Approach to the Diagnosis of Overgrowth Syndromes. AB - Overgrowth syndromes comprise a group of disorders associated with excessive growth and other features such as facial dysmorphism, developmental delay or intellectual disability, congenital anomalies, neurological problems and an increased risk of neoplasia. Recent advances in understanding the genetic basis of overgrowth syndromes has resulted in a move away from clinical classification to molecular classification of overgrowth syndromes. This review provides a structured clinical approach to patients with this group of disorders and includes most of the currently known overgrowth syndromes. PMID- 26680786 TI - Expression of Matrix Metalloproteinases and Its Inhibitor in Gastric Adenocarcinoma. AB - PURPOSE: Matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis by mediating the degradation of extracellular matrix components. A tissue inhibitor of metalloproteinases (TIMPs) has been reported to inhibit tumor invasion by means of an inactivation of matrix metalloproteinases. An imbalance between MMPs and the associated TIMPs may play a significant role in the invasive phenotype of malignant tumors. Therefore, MMPs and their inhibitors constitute promising agents for developing anticancer therapies. In the present study, the authors investigated the correlation between the expressions of TIMP-1 and MMPs, and the clinical outcome. MATERIALS AND METHODS: Immunohistochemical staining of MMP-2, -3 and -9, and TIMP-1 was performed on paraffin-embedded tissue sections of 38 early gastric carcinomas and 61 advanced gastric carcinomas. RESULTS: MMP-2 and -9 were found mainly in tumors of the intestinal type and less frequently in those of diffuse type. There were positive correlations between the presence of MMP-2 and -9 and lymph node status. There were inverse correlations between the TIMP-1 expression and tumor invasiveness. CONCLUSION: These results suggests that clinical outcomes such as the depth of invasion or metastasis are closely related to the expression of TIMP-1, MMP-2 and MMP-9. PMID- 26680787 TI - A Clinicopathological Analysis of Recurrent Gastric Cancer. AB - PURPOSE: This study was designed to investigate the correlation between the clinicopathologic characteristics and the recurrence pattern of gastric cancer and to define survival difference according to treatment modality after diagnosis of recurrence. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 4184 patients who had undergone radical surgery for primary gastric cancer from 1986 through 1996. Clinicopathologic factors were analyzed for the relationship of each factor with the pattern of recurrence. And the survival after diagnosis of recurrence was compared among the treatment modalities. RESULTS: Recurrence pattern was confirmed in 1141 patients. Loco-regional recurrence occurred in 291 patients (20.1%), peritoneal recurrence in 383 (26.5%), distant recurrence in 290 (20.1%), and mixed recurrence in 177 (12.3%), respectively. Early recurrence (less than 2 years) occurred in 767 (69.3%), intermediate recurrence (2~5 years) in 286 (25.8%), and late recurrence (more than 5 years) in 54 (4.9%). In multivariate analysis, T stage, N stage, size of tumor and perineural invasion were independent prognostic factors for recurrence. Median survival from diagnosis of recurrence was 24.2 months in the curative operation group, 7.7 months in the chemotherapy group, 7.1 months in the non curative operation group and 3.3 months in the conservative treatment group, respectively (p=0.000). CONCLUSION: The clinicopathological analysis of recurrent gastric cancer showed recurrent patterns and prognostic factors. Curative resection is suggested to have survival benefit in recurrent gastric cancer patients, although it was possible in patients with limited extent of disease. PMID- 26680788 TI - Aberrant Crypt Foci in the Background Mucosa of Colorectal Adenocarcinoma. AB - PURPOSE: This study was performed in order to determine the histologic features, incidence & frequency of the Aberrant Crypt Foci (ACFs) including mucosal abnormalities arising in the sporadic colonic cancer. MATERIALS AND METHODS: We investigated the proximal and distal colonic mucosa surrounding the tumor in 22 cases (right colon 7 cases and left colon 15 cases) of resected colonic adenocarcinoma specimen. The methylene blue- stained colonic mucosa was examined in en face preparations and rolled totally. The rolled colonic mucosa was embedded in paraffin and examined by using 4micrometer thick serial sections. RESULTS: We found one hundred twenty two ACFs. The 97 foci (78.7%) were simple hypertrophic foci (SH), composed of more elongated and larger crypts than normal with apical branching associated with goblet cell hyperplasia. The 17 foci (13.9%) were hyperplastic foci (HP) resembling hyperplastic polyp, and 7 (5.7%) were adeno matous foci (AD) while 2 (1.6%) were adenomatous foci with dysplasia (Dys). The mean number of ACFs/cm of the examined mucosa were 0.18+/-0.21 and were higher in the left colon than in the right colon (0.22+/-0.24 vs. 0.10+/ 0.10). Immunohistochemical stains for p53 and Ki-67 in these foci revealed strong and upper cryptal staining patterns in AD and Dys of ACFs, like that of neoplasia or preneoplastic condition. However, the staining intensities in SH and HP of ACFs were equal to or lower than that of normal crypts. CONCLUSION: These results suggest that grossly defined ACFs include reactive process and the majority of ACFs are induced by simple reactive alteration without preneoplastic potential; and two types of ACFs (AD and Dys) are more likely to be direct precursors of colon tumors than SH or HP. PMID- 26680789 TI - A Phase II Trial of UFT-E and Oral Leucovorin in Advanced Colorectal Cancer. AB - PURPOSE: To determine the efficacy and toxicity of UFT-E plus oral calcium leucovorin in the treatment of patients with advanced colorectal cancer. MATERIALS AND METHODS: Forty-three patients with advanced, bidimensionally measurable colorectal adenocarcinoma were enrolled in the trial. No patients had received prior palliative chemotherapy. The patients that had received previous adjuvant chemotherapy were enrolled when more than 6 months had elapsed after the completion of adjuvant therapy. Patients were treated with 300 mg/m2/day of UFT-E (tegafur-based) plus 90 mg/day of leucovorin administered orally in three divided daily doses, every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two or three courses of therapy. RESULTS: Thirty-six of forty three patients were evaluable for response; seven dropped out due to infection, toxicity and patients' refusal. Ten patients had partial responses and one patient complete response (response rate, 31%; 95% confidence interval, 16~46%). The median response duration for the UFT-E plus leucovorin regimen was 28 weeks. Grade III toxicity was seen in one case, with diarrhea. CONCLUSION: This oral regimen proved effective and well tolerated. This schema also avoided inconveniences, such as hospitalization and the use of infusion pumps, which are associated with 5-FU infusion regimens. The regimen used showed minimal toxicity, especially in the upper digestive tract, with good patient compliance. PMID- 26680790 TI - Expression of Cyclin D1 and CDK4 in DMBA-Induced Rat Ovarian Cancer. AB - PURPOSE: Ovarian cancer is a common gynecologic malignancy and the leading cause of death in women. It is typically not diagnosed until it has reached the advanced stages. We performed this study to investigate the roles of the proteins related to the G1 cell cycle in ovarian carcinogenesis. MATERIALS AND METHODS: Immunohistochemistry and Western blot were used to analyse the expression of cyclin Dl and CDK4 in 7, 12-dimethylbenzanthracene- induced ovarian cancer in rats. RESULTS: The Cyclin D1 and CDK4 labelling index was significantly higher in the ovarian cancers than in the normal ovarian surface epithelium of rats. There was no difference among the cancer types. In Western blot analyses, the expression of cyclin Dl and CDK4 in the ovarian cancers was higher than that in the normal ovarian surface epithelium. A positive correlation was observed between the expressions of the CDK4 and Cyclin D1. CONCLUSION: The upregulation of cyclin Dl and CDK4 that occurs in DMBA-induced rat ovarian carcinogenesis is likely to be associated with tumor progression. Further studies are needed to investigate the role and function of cyclin Dl and CDK4 in human ovarian cancer. PMID- 26680791 TI - Growth Suppression of Ovarian Cancer Cells by Interferon-gama. AB - PURPOSE: Growth regulation of cancer cells very frequently involves tumor suppressor gene p53, Rb and cell cycle regulator, however the molecular biologic mechanisms of growth regulation in ovarian carcinoma cells are not fully defined. To assess the mechanism of growth suppression, we treated IFN-gama in ovarian carcinoma cells. MATERIALS AND METHODS: Growth suppression by treatment of IFN gama was determined by cell proliferation assay in ovarian carcinoma cell lines. Apoptosis was determined by DNA fragmentation assay and electron microscopy. Molecular mechanism of the apoptosis in ovarian carcinoma cell by IFN-gama was further analyzed by the western blot. RESULTS: We found that IFN-gama had remarkable growth- suppressive effects in PA-1 and A2774 ovarian carcinoma cells in a time-dependent manner. Apoptosis was observed in PA-1 and A2774 cell following treatment of IFN- gama by DNA fragmentation assay and EM. The expression of IRF-1 protein from A2774 and PA-1 cell extracts was elevated by increasing the concentration of IFN-gama. IFN-gama caused an increased expression of the important apoptosis-related gene, ICE (interleukin-1beta-converting enzyme) protein in A2774 and PA-1. CONCLUSION: The coordinate induction of IRF-1 and ICE by IFN-gama in ovarian carcinoma cells suggests a functional relationship between these proteins in programmed cell death. The significance of this study is the molecular biologic background of IFN-gama considered as an alternative treatment trial of ovarian cancers. PMID- 26680792 TI - p53 Codon 72 Polymorphism and Cervical Adenocarcinoma Risk in Korean Women. AB - PURPOSE: This study was undertaken to analyze whether the p53 codon 72 single nucleotide polymorphism might be correlated with the risk and/or the prognosis of cervical cancer in Korean women. MATERIALS AND METHODS: Peripheral blood samples derived from patients with cervical squamous cell carcinoma (SCC) (n=68), cervical adenocarcinoma (n=37), cervical intraepithelial neoplasia (CIN) III (n=98) and normal controls (n=98) were examined. Germline genomic DNA was extracted from peripheral blood leukocytes and examined by PCR amplification of the specific alleles assay described by Storey et al.5 Statistical analysis was performed using the Chi-Square test or the Kaplan-Meier survival analysis, logistic regression analysis. RESULTS: The proportions of individuals who were homozygous for the proline allele, and heterozygous for the two allele, homozygous for arginine allele in each group were 15%, 47%, 38% in the SCC group; 6%, 7%, 24% in the adenocarcinoma group; 7%, 33%, 60% in the CIN III group; and 11%, 38%, 51% in the control group. No significant difference was found between the three groups (p>0.05). However there was a significant difference in the adenocarcinoma group (p<0.05). Arg/Arg homozygote reduced the risk of adenocarcinoma. No significant difference existed in 5-year survival rates in the three groups (p=0.22 in SCC, p=0.91 in adenocarcinoma). CONCLUSION: These findings suggest that Arg/Arg homozygocity of the p53 codon 72 would be a protective factor against the development of cervical adenocarcinoma. PMID- 26680793 TI - Clinical Features and Prognosis of Lung Cancer with Brain Metastasis. AB - PURPOSE: Brain metastasis is estimated to occur in 20~40% of solid tumor patients and the most common primary tumor is lung cancer. Even though the prognosis of brain metastasis is grave and the 1-year survival rate is only 15%, symptom palliations are made with whole brain radiation therapy. We retrospectively evaluated the clinical features and prognostic factors of lung cancer with brain metastasis. MATERIALS AND METHODS: From January 1987 to October 1999, 50 lung cancer patients with brain metastasis underwent whole brain radiation therapy. We reviewed the improvement in neurologic symptoms and survival according to the following parameters; performance status, histological type, presence of brain metastasis at the initial diagnosis of lung cancer, presence of extracranial metastasis, multiplicity of brain lesion, presence of primary lung symptom and treatment modalities. RESULTS: The most frequent symptom with brain metastasis was a headache (50%). Palliation of the headache and other symptoms was achieved in 81% of the patients. Median overall survival after brain metastasis was 21 weeks and the 1 year survival rate was 15%. Patients without extracranial metastasis had a longer median survival than those with, 38 weeks versus 15 weeks, respectively (p=0.01). CONCLUSION: In lung cancer with brain metastasis, neurologic symptoms can be palliated with whole brain radiation therapy, and in this study among such patients, absence of extracranial metastasis can be a good prognostic factor. PMID- 26680794 TI - Study on the Expression of Insulin-like Growth Factor II (IGF- II) in Hepatocellular Carcinoma Cells and Developing Rat Embryos. AB - PURPOSE: The insulin-like growth factor II (IGF-II) gene expresses a family of transcripts in embryonic/fetal tissue, and also highly was expressed during hepatocellular carcinogenesis. In this study, we showed that IGF-II mRNA and protein levels are detected in rat embryo, HepG2 human hepatoma cells and Chang liver cells. MATERIALS AND METHODS: This study included sections of rat embryos 7~17 days post coitum (d.p.c), HepG2 cells and Chang liver cells. Using immunohistochemistry, Northern blotting and Western blotting, we observed the expression of IGF-II in the rat embryo, HepG2 cells and Chang liver cells. RESULTS: We localized IGF-II gene products in sections of rat embryo 7~17 d.p.c by performing immunohistochemistry. The IGF-II was mainly expressed in the proximal endoderm and ectoplacental cone between 7 and 9 d.p.c. At 10 d.p.c. the expression was localized at the heart primodium as well as the proximal endoderm, and at 11 d.p.c. the IGF-II was expressed in the liver and heart. After 12 d.p.c. and 14 d.p.c., the expression was also detected in the brain, muscle and bone, and head mesenchyme, respectively. While the expression of IGF-II protein was not detected in the normal adult liver, intense staining was detected in the heart, liver and choroids plexus at 17 d.p.c. CONCLUSION: These results suggest that IGF II may act as an oncofetal protein during hepatocellular carcinogenesis and embryogenesis. PMID- 26680795 TI - A Case of a Young Woman with Hepatosplenic gamadelta T-cell Lymphoma. AB - Most T-cell lymphomas arise from mature alpabeta T-cells and commonly involve the nodes. Lymphomas bearing the gamadelta T-cell receptor (TCR) are very rare, and involve the lymph nodes minimally, if at all. Hepatosplenic gamadelta T-cell lymphoma is a recently identified, rare entity in which lymphoma cells bearing the gamadelta TCR infiltrate the sinusoids of the liver, splenic red pulp, and bone marrow. Its leukemic transformation is even more rare. Recently, we experienced a case of hepatosplenic gamadelta T-cell lymphoma in a 19-year-old woman who presented with epigastric pain, fever, massive splenomegaly, andpancytopenia. The splenectomy specimen and excisional biopsy of the liver revealed the infiltration of atypical T lymphocytes with the immunophenotypic markers of CD3 (+), CD45RO (pan-T antigen) (+), TIA-1(+), CD4(-),CD8 (-), CD56 ( ), and S100 (-) in the sinusoids of the liver and splenic red pulp. Polymerase chain reaction (PCR) showed that these cells had the expression of the TCR gama gene rearrangements. Though the pancytopenia had improved after the splenectomy, the response of chemotherapy was transient. Her disease progressed rapidly and she expired in the leukemic phase. We report a case of hepatosplenic gamadelta T cell lymphoma that developed in a young woman, along with a brief review of the literature. PMID- 26680796 TI - A Case of Primary MALT Lymphoma of the Breast. AB - Primary malignant lymphoma of the breast is rare. The incidence of primary malignant lymphomas of the breast is 0.04% to 0.5% of all malignant tumors of the breast and 0.07% of all non-Hodgkin's lymphomas, and comprises 1.7% of extranodal malignant lymphomas that occur in Western countries. The incidence of mucosa- associated lymphoid tissue (MALT) lymphoma of the breast is reported to be between 0% and 75% of all primary malignant breast lymphomas in United States and Japan, but the incidence in Korea is unknown. MALT is characterized by indolent behavior and good has a prognosis. The authors report on a patient who has a primary MALT lymphoma of the breast. She was treated by surgical excision, which was followed by radiation therapy. Histologically, her lymphoma type transformed into a diffuse large B-cell tumor after 10months. She received combination chemotherapy and achieved a complete state of remission. She then underwent autologous peripheral blood stem cell transplantation along with high dose chemotherapy. To our knowledge, this is the first case report in the literature in Korea. PMID- 26680797 TI - Expression of High Mobility Group Protein Family [HMGI(Y) and HMGI-C] in Human Breast Cancer. AB - PURPOSE: Breast cancer results from the progressive accumulation of a series of genetic alterations leading to neoplastic transformation. Recent studies have shown that a) HMGI proteins play an important role in the regulation of chromatin structure and function and b) the expression of aberrant HMGI [HMGI(Y) and HMGI C] proteins is generally correlated with malignant tumors. We tried to define the function of HMGI in carcinogenesis and we compare the expression of HMGI with known clinicopathologic parameters. MATERIALS AND METHODS: Using Reverse transcriptase-polymerase chain reaction (RT-PCR), we determined the expression of HMGI mRNA in 60 primary malignant tumors, 20 normal tissue, 13 benign tumors, and four ductal carcinoma in situ. Immunohistochemical staining of p53, ER, PR, and clinicopathological parameters were evaluated. RESULTS: The expression of the HMGI(Y) mRNA increased more in malignant tissue (90%, 54 of 60) than in benign (76.9%) and normal (65%) tissues (p=0.031). The expression of HMGI-C mRNA was visible only in malignant (48.4%, 29 of 60) and benign (23.1%, 3 of 13) tumors. The expression of HMGI-C mRNA increased more in malignant tumors than in benign tumors (p<0.001). In invasive ductal tumors (n=50), the expression of HMGI-C mRNA was observed more in high grade tumors (grade 3~81.3%, grade 1, 2~32.4%) (p=0.005). Among the prognostic parameters, only the number of mitotic figures was related to the expression of HMGI-C mRNA (p=0.046). CONCLUSION: These results suggest that a) HMGI-C gene may be correlated with the formation of breast tumors and b) the expression of HMGI-C gene may be of pathogenetic and prognostic importance in human breast cancer. PMID- 26680798 TI - Expression of Cyclooxygenase-2 in Human Breast Carcinoma: Relevance to Tumor Angiogenesis and Expression of Estrogen Receptor. AB - PURPOSE: This study investigates the COX-2 expression in human primary breast carcinomas and its relationship with both angiogenesis and the expression of estrogen receptor. MATERIALS AND METHODS: COX-2 expression, angiogenesis, and estrogen receptor expression were examined by immunohistochemical methods in 167 human breast carcinomas by using monoclonal antibodies against COX-2, CD34, and estrogen receptor protein. RESULTS: Although COX-2 was expressed in 77.8% of the breast carcinomas (130/167) regardless of histological types, it was not detected at all in benign epithelial cells. Interestingly, COX-2 expression was found to be significantly correlated with tumor angiogenesis (p=0.004), but not with estrogen receptor and other histopathologic parameters. CONCLUSION: The results suggest that COX-2 expression occurs frequently in breast tissue during transformation of benign epithelial cells to malignant cells regardless of the estrogen receptor status. COX-2 expression may play a role in tumor angiogenesis that is responsible for tumor growth and metastasis. PMID- 26680799 TI - Correlation of Ultrasonographic Findings and Pathologic Prognostic Predictions in Breast Cancer. AB - PURPOSE: Increased technologic capabilities have allowed for the expanded use of ultrasound beyond simple differentiation of a lesion as solid versus cystic nature, allowing us to classify lesions into various categories based on a number of descriptive features. The purpose of this study was to investigate whether to predict the preoperative prognosis of breast cancer through the correlation between ultrasonographic images and the grade of malignancy. MATERIALS AND METHODS: The patient population for this study consisted of 107 patients with infiltrative ductal carcinoma who were evaluated using ultrasound technology. Ultrasonographic findings were divided as follows: Type I, round or oval shape and regular border; Type II, partially round or oval shape and partially irregular border; and Type III, irregular shape and irregular border. RESULTS: 1. The frequency of grade 1 (G1) was significantly higher in the Type I group than the othergroups. 2. In the 2.0 cm sized mass, the lymph node metastasis rate was significantly lower in the Type I group than the other groups. 3. In all the groups, Estrogen receptor (ER) positivity was insignificant regardless of tumor size and type. 4. In the 2.0 cm sized mass, c-erbB-2 positivity was significantly lower in the Type I than the other groups. There was no clear difference among the three groups in tumors greater than 2.0 cm in size. CONCLUSION: These results show that our classification of ultrasonographic images reflect the grade of malignancy in terms of clinicopathological features in breast cancers less than 2.0 cm in size. Therefore, ultrasonographic findings may help predict the preoperative prognosis in T1 size breast cancer, although further study is required. PMID- 26680800 TI - Expressions of Multidrug Resistance-Related Genes in Gastric Cancer Tissue and Normal Gastric Mucosal Tissue. AB - PURPOSE: This study was conducted to evaluate the expressions of the mdr1 gene and the MRP gene in tumor and adjacent normal gastric tissues. MATERIALS AND METHODS: The specimens were obtained from 53 patients who had gastric cancer. None of these patients had received any kind of preoperative chemotherapy. The reverse transcription polymerase chain reaction and immunohistochemical stain were used to check the level of expressions of mRNAs and their associated proteins. RESULTS: Highly positive expressions of mdr1 mRNA, MRP mRNA, p glycoprotein, and MRP (multidrug resistance associated protein) were observed in the tumor and the adjacent normal tissues. Most tumor tissues coexpressed mdr1 mRNA and MRP mRNA significantly (p<0.001). The expression of these genes in the tumor was much stronger than in the normal counterpart tissues. The expression of the p-glycoprotein was correlated only with the pathological stage (p<0.05). MRP expression was correlated with lymph node metastasis (p<0.05). CONCLUSION: Normal gastric tissue showed strong physiologic expressions of the mdr1 and MRP genes. Overexpressions of these genes were observed in gastric cancer tissue. The presence of multidrug resistance should be considered when planning anticancer chemotherapy for treating gastric cancer. PMID- 26680801 TI - Genetic Alterations in Gastric Carcinomas and Adjacent Mucosa Detected by Comparative Genomic Hybridization (CGH). AB - PURPOSE: Comparative genomic hybridization (CGH) was used to detect any amplified or deleted chromosomal regions in tumors by mapping their locations on normal metaphase chromosomes. METERIALS AND METHODS: Twenty-six gastric carcinomas and their adjacent mucosa were screened for chromosomal aberrations using CGH. RESULTS: All carcinomas had chromosomal aberrations, and chromosomal material was more likely to be gained than lost. Ten out of 26 adjacent mucosa had chromosomal aberrations, and a gain was less frequently observed than a tumor (1.6/2.6). The most common gains were detected on 13q (58.3%), 8q (30.8%), 6q (27.0%), and 20p (19.2%), while the most frequent losses were detected on 17p (38.5%) and 16q (7.2%). The most commonchromosomal aberrations in the adjacent mucosa were a gain of 13q (11.5%) and a loss of 17q (11.5%). The tumors had more chromosomal gains of 2q, 3q, and 13q and more losses of 17p and 16q than the adjacent mucosa. CONCLUSION: S: The most common gain in the tumors was detected on 13q, 8q, 6q, and 20p, and the most frequent loss was on 17p and 16q. While CGH may be useful in predicting the prognosis or therapeutic decision of gastric carcinomas, further study of several candidate genes, such as DP1, FLT1, c-myb, AIB1, BTAK, is needed to clarify gastric carcinogenesis and its progression. PMID- 26680802 TI - Expression Pattern of p27 Protein in Primary Gastric Lymphomas. AB - PURPOSE: To investigate the expression pattern of p27 protein in primary gastric lymphomas. MATERIALS AND METHODS: Immunostaining for the p27 protein was performed in 16 cases of low grade mucosa-associated lymphoid tissue (MALT) lymphomas and 16 cases of high grade B-cell lymphomas of the stomach. RESULTS: All low grade MALT lymphomas were positive, however all high grade lymphomas were negative forp27 protein. Most of the monocytoid cells in the low grade lymphoma were unstained. CONCLUSION: Loss of p27 protein expression is well correlated with histologic grade and appears to be associated with the high grade transformation seen in primary gastric lymphomas. PMID- 26680803 TI - Clinical Prognostic Factors and Treatment Outcome of Aggressive Non-Hodgkin's Lymphoma in Elderly Patients. AB - PURPOSE: The aim of this study was to determine the prognostic factors and treatment outcome of for elderly patients (age>or=60 at time of diagnosis) with aggressive non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: We analyzed 52 patients diagnosed with aggressive NHL between January 1990 and May 2000. RESULTS: The patient's median age was 69 years (range: 60~92). Thirty-two (61.5%) patients were male. Patients included those with diffuse large B cell (53.8%), peripheral T cell (23.1%), AILD-like T-cell (3.8%), angiocentric (3.8%), mantle cell (3.8%), Burkitt's lymphoma (3.8%), and others (7.9%). International prognostic index (IPI) parameters were as follows: elevated LDH (60.8%), ECOG performance status>or=2 (32.7%), advanced stage (III/IV, 62.7%), and extranodal site>or=2 (11.5%). Twenty-six (50.0%) patients demonstrated a high and high intermediate IPI. The median follow-up for surviving patients was 26.6 months. The overall median survival was 22.7 months and the 2-year survival rate was 46.9%. Among the 49 patientstreated with chemotherapy, 28 (57.1%) patients achieved complete remission (CR). Univariate analysis identified 8 prognostic factors for overall survival: age<70 (P=0.04), low/low-intermediate IPI (P=0.02), good performance (P= 0.04), normal WBC (P=0.008), normal Hb (P=0.02), normal LDH (P=0.04), CR on first line therapy (P<0.001), and absence of B symptom (P=0.001). In the multivariate analysis, the independent prognostic factors for improved overall survival were age <70 (P=0.03), low/low-intermediate IPI (P=0.03), normal WBC (P=0.006), and CR on first line therapy (P<0.001). CONCLUSION: In our experience, even elderly patients (>or=60 years) with aggressive NHL can be successfully treated with conventional chemotherapy and the important prognostic factors for survival are age, IPI, initial WBC, and CR on first line treatment. PMID- 26680804 TI - Expression of Cyclin-dependent Kinase Inhibitor p21(WAF1/CIP1) in Non-small Cell Lung Carcinomas: Relationship with p53 Status and Proliferative Activity. AB - PURPOSE: The objectives of this study are to elucidate the level of p21(WAF1/CIP1) expression in non-small cell lung carcinomas (NSCLCs) and to investigate the relationship between the p21(WAF1/CIP1) expression and clinicopathologic features; p53 overexpression; and proliferative activity measured by Ki-67 expression. MATERIALS AND METHODS: The expressions of p21(WAF1/CIP1), p53, and Ki-67 proteins were analyzed by immunohistochemistry in 45 formalin-fixed and paraffin-embedded NSCLC specimens. 43 patients underwent curative resections and 2 patients had bronchoscopic biopsy specimens only. The correlations between p21(WAF1/CIP1) immunoexpression and p53 status; Ki-67 proliferative activity; and clinicopathologic parameters were analyzed statistically by chi-square or Fisher's exact test. RESULTS: p21(WAF1/CIP1) expression in the carcinoma cells was found in 28 (62%) of 45 cases. There was no significant correlation between p21(WAF1/CIP1) expression and abnormal accumulation of p53 protein. In 16 (36%) of 45 cases, p21(WAF1/CIP1) was expressed inde pendently of p53 overexpressions. p21WAF1/CIP1 expression was not associated with patient sex, smoking history, pathological stage, tumor size, histological grade or type. However, p21WAF1/CIP1 immunoreactivity was significantly higher in older individuals over 59 years and tended to occur more intensely in the more highly differentiated portion of the squamous carcinoma. Also, a positive correlation between p21WAF1/CIP1 and Ki-67 expression was observed. CONCLUSION: S: The present findings overall suggest that aberrations in the relationship between p21(WAF1/CIP1) and p53 expressions may be important in the development of NSCLCs; that a p53-independent pathway may be substantially involved in the induction of p21(WAF1/CIP1) expression in NSCLCs; and that the proliferative activity of lung cancers might be dependent on positive control of the cell cycle by p21(WAF1/CIP1). PMID- 26680805 TI - Retinoic Acid as a Radiosensitizer on the Head and Neck Squamous Cell Carcinoma Cell Lines. AB - PURPOSE: Retinoic acid is a substance that has previously been reported to increase radiosensitivity, but at concentrations likely to inhibit cell growth or to induce celluar differentiation. We choose head and neck cancer cell lines to investigate the role of retinoic acid as a radiosensitizer and to elucidate the mechanism through the changes in the expression of retinoid receptors and squamous cell differentiation marker. MATERIALS AND METHODS: Three cell lines (PCI-50, SqCC/ Y1 and UMSCC-11B) were used. 7-AAD staining for apoptosis and Western blot analysis for RAR-alpha, beta, gamma, RXR-alpha, beta, gamma and involucrin were performed after various treatments (control, beta-all-trans retinoic acid (t-RA) only (10 6 M), radiation only (3 Gy), radiation with t-RA). RESULTS: The synergistic radiosensitivity effect of t-RA was seen only radioresistant UMSCC-11B cell line. Expression of RAR-beta was induced by t-RA in maily UMSCC- 11B cell line. RAR-alpha,gamma, and RXR-alpha, beta, gamma expression were not changed in all cell lines tested. Expression of involucrin was inhibited by t-RA in PCI-50 cell line but other two cell lines were not changed by t-RA treatment. CONCLUSION: We found that only radioresistant cell line (UMSCC-11B) showed synergistic radiosensitivity effect by t-RA and this mechanism may be through RAR-beta expression induction. PMID- 26680806 TI - E-Cadherin Expression and p53 Alterations in Soft Tissue Sarcomas: A Possible Role in Epithelial Differentiation. AB - PURPOSE: We investigated the expressions of E- Cadherin and p53 in soft tissue tumors to determine their significance in sarcoma development and/or progression and to assess their potential correlation with epithelial features. MATERIALS AND METHODS: A total of 79 soft tissue sarcomas, including 10 tumors comprising epithelial components, were studied immunohistochemically in paraffin-embedded tissue sections. Further analysis was performed on 61 tumors by the application of a polymerase chain reaction technique and a direct sequence analysis procedure applied to exons 5 through 8 in the p53 gene. RESULTS: E-Cadherin was expressed at the cell-cell boundaries in 8 (10%) tumors: 5 of grade 2 and 3 of grade 3. Of these, six (being 60% of the total of 10 tumors containing epithelial elements) contained and two did not contain histologic evidence of epithelial differentiation. Overexpression of p53 was detected in 26 (33%) samples, 7 of which demonstrated mutations in the p53 gene. No association was established between E-Cadherin immunoreactivities and p53 abnormalities. Tumor grade was found to be strongly correlated with p53 alterations (p=0.01) but not with E Cadherin expression (p=0.09). CONCLUSION: These data confirm a role for altered p53 in the pathogenesis of soft tissue sarcomas and suggest a possible role for E Cadherin in the maintenance of epithelial architecture in these tumors regardless of p53 status. PMID- 26680807 TI - Discrepancies of the Values on the Withholding Futile Interventions between Physician and Family Members of Terminal Cancer Patients. AB - PURPOSE: To analyze the controversies surrounding therapeutic decision-making and the withholding of life- sustaining treatments, values held concerning therapeutic interventions of terminal cancer patients are compared between physicians and family members. MATERIALS AND METHODS: 42 advanced or terminal stage cancer patients were enrolled for the study. The questionnaires were administered to the duty doctor and the family of the patients. Questions included whether to use new agents with a 15% partial efficacy and whether to use opioid analgesics, intravenous nutrition, a feeding tube, antibiotics, and hemodialysis. Additionally, we asked about the administration of CPR, ventilator application, and euthanasia. If the family permitted, the same questionnaires were given to the patients. RESULTS: Of the 42 cases, 5 families refused to answer the questionnaire. Of the available 37 families, only 5 families permitted access to the patients. Of the 5 patients, 2 patients refused the questionnaire. Only 67.6% and 8.1% of families and the patients clearly understood the stage of cancer. The use of a new agent was accepted by 45.2% of the physicians and 45.9% of the families. The rankings of the acceptance of treatment in the physicians and in the families were similar. The concordance rate between the physicians and the families was lowest on ventilator application and CPR. 31% of the physicians and 43.2% of the families agreed on the issue of euthanasia. CONCLUSION: Values held on issues like therapeutic decision-making and the withholding of life sustaining treatments in terminal cancer patients are discordant between physicians and family members. In order to resolve controversies on the role of physicians in end-of-life decisions, the values of physicians as well as patients and their family members should be considered in the final decision-making process. PMID- 26680808 TI - A Case of Well-differentiated Papillary Mesothelioma Developing Malignant Mesothelioma with Seeding Mass on the Trocar Insertion Site of Diagnostic Laparoscopy and Malignant Change. AB - Although well-differentiated papillary mesothelioma (WDPM) is usually classified as benign, the natural history of this lesion has not been clearly established. We present a case of WDPM in 60-year old woman developing malignant mesothelioma with seeding mass on the trocar insertion site over a period of 2 years. The initial symptom exhibited by the patient was abdominal distension from massive ascitic fluid. With an impression of peritoneal carcinomatosis, we performed a diagnostic laparoscopy. On the laparoscopic finding, a small whitish nodule was found on the liver surface and the pathologic result revealed reactive mesothelial hyperplasia. At exploro-laparotomy, multiple small nodules were found on the omentum and a biopsy revealed well-differentiated papillary mesothelioma of the peritoneum. The patient underwent pelvic lymphadenectomy and omentectomy of the colon and was followed for 2 years without any further treatment. Subsequently, she presented with abdominal distention with massive ascites and palpable abdominal wall mass at the previous trocar insertion site. Malignant mesothelioma was confirmed histologically via re- exploration. The rare transformation of well-differentiated papillary mesothelioma into a typically malignant diffuse mesothelioma and the unusual seeding on trocar insertion site prompted us to report this case. PMID- 26680809 TI - Annual Report of the Central Cancer Registry in Korea-1999: Based on Registered Data from 128 Hospitals. AB - PURPOSE: The Central Cancer Registry Center in Korea (KCCR) conducted a nationwide hospital-based cancer registry to provide basic statistical data on cancer. MATERIALS AND METHODS: In 1999, 128 hospitals participated in the cancer registry program. All cancer registry data, which was submitted from the participating hospitals by diskettes during the year, were reviewed and analyzed by the committee members who were all Board-qualified clinical oncologists and pathologists. To avoid duplication, every resident registration number was compared by a computer. Cases that had been diagnosed by a histological examination were preferentially chosen for inclusion in this data. RESULTS: Of 94,003 cases that were registered, there was a total of 8,452 (9.0%) duplication cases which were excluded. Of the remaining 85,551 cases, there were 3,231 cases (3.8%) of carcinoma in situ (morphology code/2) which were excluded. A final total of 82,320 cases were analyzed. Of the analyzed cases, 46,908 (57.0%) were males and 35,412 (43.0%) were females. The leading age groups in the order of their relative frequency were those who were 60~64 years of age (15.3%), followed by the 55~59 age group (13.8%). The six leading primary cancer sites in the order of their relative frequency were stomach (20.7%), followed by the bronchus and lung (12.1%), the liver and intrahepatic bile duct (12.0%), the colorectum (9.9%), the breast (6.4%), and then the uterine cervix (5.0%). In males, the five leading primary cancer sites were the stomach (24.2%), the liver and intrahepatic bile duct (16.3%), the bronchus and lung (16.1%), the colorectum (9.7%), and the urinary bladder (3.3%). In females, the stomach (16.2%) was the most common cancer site, followed by the breast (14.7%), the uterine cervix (11.6%), the colorectum (10.2%), and the thyroid (6.8%). Among the 1,077 cases of childhood malignancies, leukemia (35.4%), CNS tumors (16.7%), malignant lymphomas (7.0%), and sympathetic nervous system tumors (6.9%) were the most common cancer types. CONCLUSION: We analyzed and report the KCCR data from 128 nationwide hospitals during 1999. PMID- 26680810 TI - Phase II Trial of Vinorelbine and Cisplatin Chemotherapy in Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: Platinum-based chemotherapy has conferred a modest but significant survival benefit and the introduction of newer drugs has led to achieve higher response rate in patients with advanced non-small cell lung cancer (NSCLC). We performed a phase II trial in order to evaluate the efficacy and toxicity of combination chemotherapy with vinorelbine (Navelbine) and cisplatin in advanced NSCLC. MATERIALS AND METHODS: Patients with previously untreated, unresectable stage IIIB or IV NSCLC with measurable lesion (s) were eligible for entry into the study. NP chemotherapy consisted of intravenous vinorelbine 25 mg/m2, on day 1 and 8, and intravenous cisplatin 80 mg/m2 on day 1; this cycle was repeated every three weeks. RESULTS: A total of 33 patients were enrolled in the study between July 1999 and Feb 2000. Of the 30 patients deemed eligible for analysis, thirteen patients achieved a partial response and thirteen showed a stable disease. The overall response rate was 43.3%. The median duration of response was 5.7 months (95% CI: 2.8~8.5 months). The median time to progression was 7.6 months (95% CI: 5.5~9.7 months) and the overall median survival time was 15.1 months (95% CI: 9.8~20.4 months) in the intent-to-treat analysis. Chemotherapy related grade 3 or 4 toxicities were anemia in 1.5%, leukopenia in 4.5%, nausea/vomiting in 2.3%, alopecia in 13.3%, and neurotoxicity in 3.3%. CONCLUSION: The combination of vinorelbine and cisplatin chemotherapy seems to be active and fairly tolerable in patients with advanced NSCLC. PMID- 26680811 TI - Combination Chemotherapy with Mitomycin C, Vinorelbine, and Cisplatin (MVrP) in Patients with Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: A phase II study was conducted in patients with advanced non-small cell lung cancer (NSCLC) in order to evaluate the efficacy and toxicity of the combination chemotherapy regimen of mitomycin C, vinorelbine, and cisplatin (MVrP). MATERIALS AND METHODS: Between June 1996 and December 2000, fifty-nine patients with unresectable stage IIIB to IV, pathologically documented NSCLC were enrolled in this study. One cycle consisted of mitomycin C 10 mg/m2 i.v. day 1, vinorelbine 30 mg/m2 i.v. days 1 & 15, and cisplatin 80 mg/m2 i.v day 1 and the next cycle consisted of vinorelbine 30 mg/m2 i.v. days 29 & 43, and cisplatin 80 mg/m2 i.v day 29. Each cycle was alternated and treatments were repeated every 8 weeks. RESULTS: We were able to evaluate fifty-three of 59 patients. Objective responses were seen in 22 (41.5%) patients (CR 0%, PR 41.5%). The median duration of response was 13.7 weeks and the median time to progression was 17.7 weeks. The median overall survival was 45.6 weeks. There was a significantly longer survival seen in responders (p=0.041). The toxicities of this regimen were acceptable without treatment related toxic death. CONCLUSION: This study suggests that a combination regimen of mitomycin C, vinorelbine, and cisplatin is relatively effective and well tolerated for the treatment of advanced NSCLC. PMID- 26680812 TI - Effects of Polyamines on TNFalpha- or Tamoxifen-induced Apoptosis in Human Breast Cancer Cells. AB - PURPOSE: To investigate the effects of polyamines on tumor necrosis factor alpha (TNFalpha)-or tamoxifen (TAM)-induced apoptosis in estrogen receptor (ER) positive MCF- 7 and ER-negative MDA-MB-231 human breast cancer cells. MATERIALS AND METHODS: Cell viability was assessed by using MTT assay. Reactive oxygen species (ROS) generation was measured using 2', 7'-dichlorofluorescin diacetste (DCFDA) by fluorescence plate reader. DNA fragmentation was assessed by 1.5% agarose gel electrophoresis. RESULTS: TNFalpah and TAM showed significant dose- and time- dependent inhibitory effects on the growth of MCF-7 human cells. However, the growth of MDA-MB-231 cells were not inhibited by TNFalpha or TAM treatment. The generation of ROS was increased in dose-and time-dependent manner by TNFalpha treatment in MCF-7 cells. Polyamines, especially spermine suppressed TNFalpha-induced ROS generation in MCF-7 cells. Antioxidant effects of polyamines were also demonstrated by DNA fragmentation, cell morphology as well as ROS generation assay. Polyamines also blocked TAM-induced cell death in MCF-7 cell. However, MDA-MB-231 cells showed resistance to the cytotoxic effects of TNFalpha or TAM. CONCLUSION: These results suggest that polyamines may prevent TNFalpha or TAM-induced apoptosis in MCF-7 human breast cancer cells. PMID- 26680813 TI - The Reliability of Histoculture Drug Response Assay (HDRA) in Chemosensitivity Tests for Breast Cancer. AB - PURPOSE: Cancers are highly individual in their response to chemotherapy, however attempts to predict tumor response to drugs using in vitro cell culture have largely failed. A new technology, the histoculture drug response assay (HDRA), appears to have solved many previous problems. The purpose of this study is to evaluate the reliability of HDRA in a chemosensitivity test for breast cancer. MATERIALS AND METHODS: Tumor specimens from breast cancer patients were evaluated by HDRA using different chemotherapeutic agents. Each specimen was tested using a blind method in order to determine the reproducibility of HDRA results for the same tissue and with a triplicated assay in order to determine reproducibility by different examiners. The evaluative power of this assay and the chemosensitivity of drugs for each specimen was determined. RESULTS: Specimens of 92.9% (65/70) were successfully cultured and evaluated for chemosensitivity. The reproducibility of HDRA for the same tissue was 75% (100% agreement) and 100% (over 70% agreement), respectively. And the reproducibility by different examiners was 78.9% (100% agreement) and 94.7% (over 70% agreement), respectively. Each specimen demonstrated a response to at least one agent. CONCLUSION: The evaluative power and reproducibility of HDRA were high, therefore it might serve as a reliable clinical method for chemosensitivity testing. However, there is a need for clinical trial in which patients are initially randomized for treatment either by HDRA direction or by clinician's choice. PMID- 26680814 TI - Combined Chemotherapy and Radiotherapy for Primary CNS Lymphoma. AB - PURPOSE: This study was performed in order to evaluate the effectiveness of combined chemotherapy and radiotherapy (RT) in primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: From January 1995 to August 1999, 21 patients with a diagnosis of PCNSL were treated with combined chemotherapy and radiotherapy. Their median age was 47 years with range of 19 to 78 years. Twelve patients were male and nine patients were female. All patients were immunocompetent and they had no evidence of systemic lymphoma. All patients underwent placement of an Ommaya reservoir and recieved a combination regimen using pre-RT systemic and intra-Ommaya methotrexate (MTX), 40 Gy whole-brain RT with a 14.4 Gy boost, and 2 courses of post-RT high-dose cytarabine. The median follow-up period of all patients and survived patients were 22 months and 36 months, respectively. RESULTS: The median overall survival duration was 21 months and the overall two- and four-year survival rates were 51% and 43%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were achieved in 12, 3, 1, and 5 patients, respectively. All nine patients without CR expired within 1-31 months (median 6 months). Two patients among the patients with CR developed recurrence after 13 and 14 months, respectively. The location of recurrent disease was within the port of radiation boost. Survival was influenced by age, performance status, and CR. There was one episode of MTX neurotoxicity and hepatotoxicity,respectively. CONCLUSION: Combined chemotherapy and radiotherapy was an effective treatment for PCNSL, and was associated with a minimum toxicity. However, we must pay attention to the recurrence and late toxicity, particularly within two years following treatment. PMID- 26680815 TI - Effects of Cyclooxygenase and Lipoxygenase Inhibitors on the Proliferation of Colon Cancer Cells and Their Production of Eicosanoids. AB - PURPOSE: Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of colon cancer and that the inhibition of colon cancer is mediated through modulation of eicosanoid production. The present study examined the effect of cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors on colon cancer cell growth and prostaglandin E(2) (PGE(2)) or leukotriene B(4) (LTB(4)) secretion by these cells. MATERIALS AND METHODS: The human colon adenocarcinoma cell lines, Caco-2 and HT-29 cells, were cultured in serum-free medium with various concentrations of indomethacin, piroxicam or esculetin in the presence of 0.15nM or 10nM linoleic acid. Cell number was estimated by MTT assay and PGE(2) and LTB(4) were analyzed by enzyme immunoassay. RESULTS: The NSAIDs inhibited cell proliferation in a concentration dependent manner. However, the potency and efficacy of each drug varied in the two cell lines. In Caco-2 cells, the effect of esculetin was higher than that of indomethacin, and piroxicam had no effect. In HT-29 cells, only indomethacin significantly inhibited cell proliferation. All three agents inhibited PGE(2) secretion in a dose-dependent manner; the effect of indomethacin was highest and that of esculetin lowest. The secretion of LTB4 was increased by indomethacin and piroxicam but decreased by esculetin. The effects of these drugs on cell proliferation and eicosanoid secretion were not influenced by linoleic acid concentrations in the culture media. Neither exogenous PGE2 nor LTB4 affected cell proliferation. The results of Pearson correlation analyses revealed that changes in cell proliferation were somewhat related to both concentrations of NSAIDs in the culture medium and production of PGE(2) and LTB(4). CONCLUSION: The present data suggests that the anti-proliferative effect of NSAIDs may not be entirely attributed to changes in the production of PGE2 and/or LTB4 in the two colon cancer cell lines. These NSAIDs may inhibit cell proliferation largely independent of their ability to modulate eicosanoid synthesis. PMID- 26680816 TI - Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5 Fluorouracil-Pretreated Patients with Metastatic Colorectal Cancer. AB - PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer who previously treated with 5-FU-based chemotherapy. MATERIALS AND METHODS: Between April 1999 and January 2001, thirty-two patients were enrolled in this study. Oxaliplatin 130 mg/m2 was given intravenously (IV) on day 1 as was 5-FU 500 mg/m2 IV followed by continuous infusion of 5-FU 3,000 mg/m2 and LV 100 mg/m2 for 48 hours administered every 3 weeks. Six patients had received 5-FU as an adjuvant setting and 26 patients as a palliative regimen. RESULTS: The median age of the patients was 50 years (range; 19-69) and the dominant sites of metastasis were the liver, lung or both in 9, 5 and 2 patients respectively. In 30 evaluable patients, the overall response rate was 27% including 1 complete response and 7 partial responses. The median response duration was 28 weeks (95% confidence interval; 22~34 weeks) and the median progression free survival of all patients was 24 weeks (95% confidence interval; 15~33 weeks). A median 5 cycles (range; 2~9) and total 155 cycles were performed in 32 patients. 150 cycles were evaluable for toxicity. The most common hematologic toxicity was grade 1~2 anemia in 78 cycles (52%). Leukopenia (39%) and thrombocytopenia (23%) were fully reversible. The most common non-hematologic toxicity was nausea/vomiting (43/30%) followed by diarrhea (23%), hepatotoxicity (21%) and neurotoxicity (21%). One patient ceased therapy due to grade 4 diarrhea. No other severe toxicity interrupted this treatment. CONCLUSION: Oxaliplatin, 5-FU and LV in combination showed significant activity in previously treated metastatic colorectal cancer with favorable toxicity. PMID- 26680817 TI - Geographical Variation of Liver Cancer Mortality in Korea (1992-1998). AB - PURPOSE: The death rate of liver cancer in Korea has been reported as one of the highest in the world. This study was conducted to investigate geographical variations of liver cancer mortality in Korea in order to obtain insight into possible environmental factors related to liver cancer. MATERIALS AND METHODS: The sex-specific standardized mortality ratios (SMRs) of liver cancer were calculated for 168 basic administrative units in Korea based upon the vital statistics for the seven years 1992 to 1998, as well as the sex- and age-specific population of each area for 1995. The SMRs were classified into six categories and depicted on a map for each sex. RESULTS: The southern provinces showed clearly higher mortality rates as compared to the rest of the country in both males and females. Looking at the maps in detail, there was a geographical variation even within the southern provinces. The areas around large rivers, some costal areas, and costal islands showed a high mortality rate. Even in the middle and northern provinces, the eastern costal areas showed relatively higher mortality rates as compared to inland areas. Conversely, some southern areas known for low levels of pollution showed relatively lower mortality rates. CONCLUSION: This finding suggests a possible relationship between liver cancer and water-related foods from polluted rivers or seas. Further studies should be performed in order to clarify which factors cause this geographical variation. PMID- 26680818 TI - Effect of Phospholipase C-gamma1 Overexpression on the Protein Level of Waf1, PCNA, and Cyclin B1 Following Ultraviolet C Irradiation. AB - PURPOSE: It has been demonstrated that PLC-gamma1 is overexpressed in many tumor cells, and that overexpression of Phospholipase C (PLC)-gamma1 is associated with tumor progression. In order to understand the effect of the PLC-gamma1 overexpression on the regulation of cell cycle regulators following DNA damage, we analyzed the expression level of PCNA, cyclin B1, and p21 Waf1 after ultraviolet C (UVC) irradiation in PLC-gamma1-transfected PC12 cells. MATERIALS AND METHODS: PC12 and 3Y1 cells, transfected with empty vector or rat PLC-gamma1 cDNA, were used for this study. Following UVC irradiation, cell cycle progression was analyzed by flow cytometry and protein expression was detected by Western blotting. RESULTS: Waf1 protein was markedly down-regulated, whereas PCNA and cyclin B1 was up-regulated in PLC-gamma1 overexpressed-cells as compared to the vector transfected-cells. When the cells were irradiated with UVC, PCNA was slightly increased within 3-hours of the UV irradiation and then was markedly decreased in Vector/ PC12 cells, while it remained high until 37 hour after UVC in PLC-gamma1/PC12 cells. In contrast, cyclin B1 was gradually decreased following UVC irradiation in both cells. CONCLUSION: The overexpression of PLC gamma1 affects the expression level of PCNA after UVC irradiation. We proposed that the overexpression of PLC-gamma1 may contribute to the UV-induced genomic instability by up-regulating the expression of PCNA. PMID- 26680819 TI - Clinical Analysis of PTEN, p53 and Her-2/neu Expressions in Thyroid Cancers. AB - PURPOSE: The dual-specificity phosphatase PTEN/ MMAC1/TEP1 has recently been identified as the tumor suppressor gene most frequently mutated and/or deleted in human tumors. However, PTEN mutations have rarely been detected in sporadic thyroid cancers. Therefore, this study investigated the PTEN expression of thyroid cancer and the relationship between PTEN, clinical status and other biologic factors such as HER-2/neu and p53. MATERIALS AND METHODS: The study samples consisted of 62 thyroid cancer specimens and 24 benign thyroid tumor specimens from patients who were operated on the Department of Surgery, Uijongbu St. Mary's hospital during the 5 years from January 1995 until January 2000. All tumors were studied by immunohistochemical staining using monoclonal antibodies against PTEN, HER-2/neu and p53. The results were analyzed statistically. RESULTS: PTEN protein was found to be under-expressed more frequently in thyroid cancers (29%) than in benign thyroid tumors (4.2%). The reduction in PTEN expression in thyroid cancers was not significantly related with the recorded clinical factors such as size, age, lymph node metastasis and p53, except for HER 2 which was found to be significantly related (p=0.001). HER-2 over- expression was noted in thyroid cancer (83.8%) more frequently than in benign tumors (16.7%). CONCLUSION: This study has demonstrated that the under-expression of PTEN protein and the over-expression of HER-2 protein may play a role in the carcinogenesis and development of thyroid cancer. PMID- 26680820 TI - A Case of Intracardiac Lymphoma as a Presentation of Non Hodgkin's Lymphoma. AB - Lymphomatous involvement of the heart is extremely rare at initial diagnosis and presentation of malignant lymphoma. Worldwide, only a few cases have been diagnosed and treated during life and only four cases were diagnosed before death in Korea. We report a case of non-Hodgkin's lymphoma with two right atrial masses detected by chest computed tomography and transesophageal echocardiography. The patient was an 80 year- old man and the presenting symptoms included generalized weakness, weight loss, constipation and low abdominal pain. For diagnosis, the mass of the perinephric area was biopsied under ultrasonographic guidance, and pathologically it was determined to be malignant lymphoma, diffuse large B cell type. The patient was treated with continuous low dose cyclophosphamide and prednisolone vice standard chemotherapy because of advanced age and renal dysfunction. After 2 months of treatment the masses in the atrium and the intraabdominal masses disappeared. PMID- 26680821 TI - A Phase II Study of Genexol(R) (paclitaxel) in Metastatic Breast Cancer. AB - PURPOSE: Paclitaxel is a very effective agent in the treatment of breast cancer. Samyang Corporation has developed its own process to produce paclitaxel in a large volume using plant cell culture technology. To evaluate the efficacy and safety of Genexol(R) in patients with metastatic breast cancer who have failed to respond to standard therapy, we performed a prospective, multi- center phase II clinical trial. MATERIALS AND METHODS: Patients with metastatic breast cancer were included in this study. Enrollees were required to have histologically confirmed breast cancer with bidimensionally measurable metastatic disease. Genexol(R) was administered at 175 mg/m2 as a 3-hour intravenous infusion every 3 weeks. All patients were premedicated with hydrocortisone, pheniramine maleate, and H2 blocker 30 minutes prior to paclitaxel. We planned to administer at least 4 courses of paclitaxel unless there was disease progression or unacceptable toxicity and to continue treatment up to a total of 6 courses in cases of objective response following 4 courses. RESULTS: The median duration of follow-up was 8.9 (2.07~13.7) months. Forty-five patients were registered and 43 were eligible. The performance status of patients was ECOG 0~1 in 39 patients (90.7%) and 2 in 4 (9.3%). The location of metastases at the start of the study were the lung (15 patients), liver (8 patients), lymph nodes (22 patients), and other (7 patients). Among the 40 evaluable patients, 15 patients obtained partial responses (PRs) (37.5%, 95% CI: 22.5~52.5%). The median duration of response was 11.67 (4.1~11.7) months and the median time to progression was 7.73 (2.8~11.7) months. The median survival time was not reached at 13.7 months, and the overall survival rate at 13.7 months was 70.1%. The hematologic toxicity was primarily neutropenia with grade 3 or 4 in 10 patients (23.3%). The grade 3 or 4 non hematologic toxicities included alopecia (17, 39.5%), myalgia (2, 4.7%), neuropathy (2, 4.7%), and pruritus (1, 2.3%). Mild hypersensitivity reaction was observed in 2 patients, although it did not cause withdrawal of the test drug. CONCLUSION: The results suggest that the Genexol injection is an effective anticancer formulation for the treatment of metastatic breast cancer and toxicity is acceptable. PMID- 26680822 TI - Clinical Analysis of Phyllodes Tumor of the Breast. AB - PURPOSE: Phyllodes tumors are fibroepithelial mammary lesions that tend to behave in a benign fashion but may undergo sarcomatous transformation. They account for 0.3 to 0.5 percent of all breast tumors. Their behavior is not well understood by many clinicians. MATERIALS AND METHODS: We retrospectively reviewed the clinical, radiologic, and pathologic finding and treatment modality of 31 patients of phyllodes tumor diagnosed at the Breast Clinic, Gachon Medical School Gil Medical Center between July 1992 and July 2000. RESULTS: Pathologically, 6 patients (19.3%) had malignant tumor and 25 patients (80.7%) had benign lesions. All were women with average age of 36 years. The patients with malignant tumors tended to be older and had larger tumors and shorter duration. For preoperative diagnosis, we used mammography, sonography, and MIBI Scintimammography, fine needle aspiration cytology and biopsy. All these diagnostic methods suggested the diagnosis of phyllodes tumors in only 8 cases (26%). All patients received surgical treatment: excision in 21 cases, wide excision in 3 cases, simple mastectomy in 5 cases, and simple mastectomy with axillary lymph node dissection 2 cases. One patient with malignant tumor, two patients with borderline tumor and three patients with benign tumor experienced recurrence (19.3%). CONCLUSION: None of the clinical or radiologic characteristics was useful in predicting for phyllodes tumor. Phyllodes tumors were difficult to make proper preoperative diagnoses and to differ malignant tumor from a benign one. This led to a simple excision and resulted in high local recurrence. We suggest that the initial or subsequent wide excision is an appropriate surgery to decrease the recurrence. PMID- 26680823 TI - Sarcoma and Sarcomatous Metaplastic Carcinoma of the Breast. AB - PURPOSE: Primary sarcoma and SMC (sarcomatous metaplastic carcinoma) of the breast are very rare tumors, accounting for less than 1% of all breast malignancies. There are many controversies concerning the biological characteristics, prognosis and optimal treatment of these tumors owing to the rarity of incidence. The aims of this study were to elucidate the clinicopathologic characteristics of these tumors and to assist in elucidating the optimal treatment plan for the disease. MATERIALS AND METHODS: 13 cases of primary sarcoma and 10 cases of SMC that had been treated at KCCH between 1984 and 2001 were retrospectively reviewed. Phyllodes tumors were excluded from our study. RESULTS: Among the 13 cases of primary sarcoma included, stromal sarcoma occurred in 5 cases, osteosarcoma in 3 cases, angiosarcoma in 3 cases and spindle cell sarcoma in 2 cases. The mean age of the patients with primary sarcoma and SMC was 39.7 years and 55.1 years respectively (p=0.002). When survival rates were compared according to histologic types, size of tumor, histologic grade, type of surgery and use of adjuvant therapy, both size of tumor (p=0.0256) and histologic grade (p=0.0197) were shown to be prognostic factors. CONCLUSION: There were no significantly different features between primary sarcoma and SMC in terms of biologic characteristics or survival rates, with the exception that patients with SMC were older than those with primary sarcoma. Histologic grade and size of tumor were significant prognostic factors of these tumors. PMID- 26680824 TI - Efficacy of Low-dose Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with low-dose paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: Chemotherapy-naive patients with unresectable, pathologically proven non-small cell lung cancer were eligible for inclusion in the study. Patients received paclitaxel (145 mg/m2 iv 3 hour D1) and cisplatin (60 mg/m2 iv D1) every 3 weeks. RESULTS: Forty-two patients were enrolled between February 2000 and February 2001. The median age was 53.5 years. Patients with adenocarcinoma numbered 29, squamous cell carcinoma 7, large cell carcinoma 3, and undifferentiated carcinoma 3. Seventeen patients had stage IIIB, 19 had stage IV disease and the remaining 6 displayed recurred disease after previous surgical resection. Four patients terminated treatment early because of hypersensitivity (1) and severe emesis (3). Of the 38 evaluable patients, 14 had PR and the response rate was 36.8%. Among partial responders, 6 patients received additional chest radiation. The median duration of response was 47.9 weeks and the median overall survival was 54.0 weeks. Of the total 176 courses, 14 were delayed, 22 required dose reduction, and grade 3~4 neutropenia occurred in 5.6% of courses. Only one episode of neutropenic fever developed and there were no treatment- related mortalities. Other toxicities were generally mild. CONCLUSION: The combination chemotherapy with low-dose paclitaxel and cisplatin was effective and tolerable in patients with advanced non-small cell lung cancer. PMID- 26680825 TI - Clinical Features of Neuroendocrine Lung Cancer. AB - PURPOSE: This study was performed to investigate the clinical features of neuroendocrine lung cancer. MATERIALS AND METHODS: We performed a retrospective review of the histopathology and clinical information of 21 patients diagnosed as having neuroendocrine lung cancer between 1995 and 1999. RESULTS: Nineteen cases were male and 2 were female. The median age was 64 years (range: 45~80). Pathologic classification were atypical carcinoid (AC) in 2 cases, large cell neuroendocrine carcinoma (LCNEC) in 7 cases, and intermediate cell neuroendocrine carcinoma (ICNC) in 12 cases. Nine patients received tumor resection as first line therapy; adjuvant chemotherapy was given to 3 patients. Concurrent chemoradiotherapy was given to 1 patient. Six patients received palliative chemotherapy. The chemotherapy regimen included etoposide cisplatin in 5 cases and vinorelbine+cisplatin in 1 case. The median survival times were 11, 16 and 59 weeks for AC, LCNEC and ICNC, respectively. The estimated 2-year survival rates were AC 0%, LCNEC 22% and ICNC 31%. CONCLUSION: Surgery may have a positive effect on survival in patients with early stage cansers. Further investigation is required to improve survival in cases of advanced stage cancer. PMID- 26680826 TI - Reoperation of Recurrent Gastric Cancer. AB - PURPOSE: The aim of this study was to evaluate the outcome of reoperation in recurrent gastric cancers. MATERIALS AND METHODS: We conducted a retrospective analysis of 86 patients who underwent reoperation for recurrent gastric cancer. We reviewed the time interval between first operation and reoperation, as well as the recurrence pattern, type of reoperation, and survival following reoperation. RESULTS: the average time to reoperation following curative resection was 27.8+/ 25.9 months (median 18.4 months). Fifty-three cases (61.6%) of reoperation were performed within 2 years follwoing the first operation. The most common reason for reoperation was intestinal obstruction followed by gastric remnant recurrence and intra-abdominal mass. Complete resection was possible in 14 cases (16.3%) and a palliative procedure such as partial resection or bypass procedures was performed in 54 cases. In 18 cases (20.9%), simple lapalotomy was done without any aid. The most common site of recurrence was the peritoneum followed by the gastric remnant, distant lymph node and hematogenous liver metastasis. Operative mortality was 10.5%. Excluding the 9 cases of operative mortality, the mean survival time after reoperation was 15.4+/-2.5 months (mean 8.6 months). Survival following complete resection was much longer than palliative procedure and exploration only (37.9+/-8.7 vs 10.9+/-1.5 vs 4.7+/-0.8 months, p=0.000). CONCLUSION: The complete resection of recurrent gastric cancer can prolong survival. Early detection of localized recurrence is important in order to increase the chance of complete resection. PMID- 26680827 TI - Clinical Significance of Peripheral Blood CEA mRNA Expression in Gastric Cancer Patients Underwent Curative Resection. AB - PURPOSE: Recent advances in molecular technology have made it possible to detect small numbers of circulating tumor cells in the peripheral blood or bone marrow. Carcinoembryonic antigen (CEA) is an oncofetal antigen that is expressed in epithelial tumor cells. CEA mRNA may be a reliable marker for the detection of tumor cells in the peripheral blood of patients with epithelial cancer. MATERIALS AND METHODS: We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using RT-PCR (Preop, Post op 15 day, 2 months (m), 4 m, 6 m, 8 m, 10 m, 12 m). The clinical characteristics, serum CEA level and immunohistochemical staining of tumor tissue were also evaluated. Patients were followed up for 6 to 12 months. RESULTS: There was no significant relationship seen between CEA mRNA RT-PCR positivity in the peripheral blood and sex, stage, serum CEA level or immunohistochemical staining for CEA antigen, During follow up,eight patients experienced recurrence; were positve for CEA mRNA RT-PCR recurrence was seen in 66.7% (6/9) of the patients who before clinical recurrence as compared to 5.4% (2/37) of patients who were negative (p=0.0002). Serial changes of CEA mRNA RT PCR correlated with clinical recurrence; 100% in the positively converted group (3/3), 0% in the negatively converted group(0/18), 50% in all positive group (3/6) and 10.5% in all negative group (2/19) experienced recurrence, respectively. CONCLUSION: RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric cancer patients and may be useful in determining patients at high risk for recurrence. However, definitive correlation with recurrence certainly requires a longer follow up duration in further studies. PMID- 26680828 TI - Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Locoregional Esophageal Cancer. AB - PURPOSE: The object of this study is to evaluate the efficacy and toxicity of induction chemotherapy followed by concomitant chemoradiotherapy in locoregional esophageal cancer. MATERIALS AND METHODS: Between December 1992 and December 1999, 43 patients with locoregional esophageal cancer were enrolled in this phase II trial. Patients were treated with 2-cycles of induction chemotherapy followed by concomitant chemoradiotherapy. F-P chemotherapy consists of 1,000 mg/m2/Day of 5-FU as continuous infusion on day 1~5 and 80 mg/m2 of cisplatin as an intravenous bolus on day 1 and was repeated every 3~4 weeks. All patients received 60 Gy of external beam radiation concomitantly with F-P chemotherapy; intraluminal brachytherapy was added in 12 patients. A total of 4 cycles of chemotherapy were delivered. No further treatment was planned in patients who achieved complete remission after completion of the treatment. RESULTS: Among the 43 patients entered, 35 patients completed the protocol. Of the 35 evaluable patients, 12 patients (34%) achieved complete response and 13 patients (37%) achieved partial response. In 26 of 33 patients, dysphagia was improved. At a median follow-up of 22 months, the 2-year and 5-year survival rates were 39% and 19%, respectively. The median survival duration of the complete responder group was 69 months (4~100 months) and the 2-year survival rate of the complete responder group was 82%. Toxicities were tolerable, comprised of mucositis and cytopenia. CONCLUSION: Induction chemotherapy followed by concurrent chemoradiotherapy in locoregional esophageal cancer is well tolerated and effective. PMID- 26680829 TI - Mutation of Ha-ras Oncogene in Rat Salivary Gland Tumors Induced by DMBA. AB - PURPOSE: The incidence of salivary gland tumor is approximately 2% among all head and neck tumors, of which malignant cases account for only about 5%. Much research has been performed in order to clarify the mechanism of oncogene activation, however salivary gland tumors remain understudied. We performed this study in order to characterize the ras gene in these tumors. MATERIALS AND METHODS: We treated white rats with 7, 12-dimethylbenz[a]anthracene (DMBA) and confirmed the occurrence of salivary gland tumors after ten to thirty weeks. Isolated genomic DNAs from tumor tissues were added to NIH 3T3 cells. In order to detect Ha-ras mutations, we performed a two-step PCR-RFLP and 7analyzed the mutated sequences. RESULTS: We induced salivary gland tumors by DMBA treatment in white rats. Isolated DNAs from the tumor tissues transformed the NIH 3T3 cells. Point mutations were observed in codons 12 and 61 of the Ha-ras oncogene. The total frequency of point mutations was 13.9% in DMBA-induced salivary gland tumors in rats. CONCLUSION: Our results demonstrate that a variety of cancers ras oncogene mutations were also found in salivary gland tumors. We confirmed that a point mutation of the Ha-ras oncogene in a DMBA-induced salivary gland tumor occurs at a frequency of 13.9%. PMID- 26680830 TI - Evaluation of E1B-mutant Replicating Adenoviruses for Cancer Gene Therapy. AB - PURPOSE: Gene-attenuated replication-competent adenoviruses are emerging as a promising new modality for the treatment of cancer. In an effort to continually improve upon cancer gene therapy, we have modified gene- attenuated replication competent adenoviruses so as to cause them to replicate efficiently and lyse the infected cancer cells more effectively. MATERIALS AND METHODS: We modified the E1 region of the adenovirus (Ad) systematically, generating Ad-deltaE1B19, Ad deltaE1B55, Ad-deltaE1B19/55, and Ad-WT. The cytopathic effects (CPE) and viral replication of these four gene modified adenoviruses were compared, and the morphology and DNA fragmentation of the infected cells was evaluated. RESULTS: Among the constructed adenoviruses, E1B 19kD-inactivated adenovirus (Ad deltaE1B19) was the most potent, inducing the largest-sized plaques and markedCPE. Moreover, cells infected with Ad-deltaE1B19 showed complete cell lysis with disintegrated cellular structure whereas cells infected with Ad-WT maintained intact cellular and nuclear membrane with properly structured organelles. TUNEL assay was also used to monitor DNA integrity, and a more profound induction of apoptosis was observed in the Ad-deltaE1B19 infected cells in comparison to wild type adenovirus infected cells. CONCLUSION: We demonstrate that the inactivation of the E1B19kD gene in a replicating adenovirus leads to increased CPE, rapid viral release, improved cell-to-cell viral spread and increased induction of apoptosis. PMID- 26680831 TI - Proportion of Death Certificate Only Cases and Its Related Factors, Kwangju Cancer Registry (KCR). AB - PURPOSE: To ascertain the factors associated with the proportion of death certificate only (DCO) cases contained in the Kwangju Cancer Registry (KCR) that are not as yet in the good range. MATERIALS AND METHODS: The distribution of DCO cases was analyzed by sex, age, cancer site, histological verification (HV) as well as the physician's death certificate status. RESULTS: All cases (n=4,243) in Kwangju diagnosed as having cancer between 1997 and 1998 were registered with the KCR. Death certificates (n=2,390) reporting cancer as the causes of death were collected from the National Statistics Office and reviewed with hospital data linkage and a total of 590 cases were registered as DCO. DCOs accounted for 12.2% (male 12.8%, female 11.5%) of all registrations in Kwangju, 1997~1998. The proportion of DCO cases was high in subjects under 15 (male13.5%,female 9.4%) as well as those 75 and over (male 20.3%, female 27.2%). For cancer sites, the proportion of DCO cases was high (over 10%) for liver, bronchus-lung, esophagus and pancreas and low (under 3%) for skin, bladder, uteri cervix and breast. The proportion of DCO cases was inversely associated with HV%. When the death certificate was issued by physician, the possibility of DCO decreased. CONCLUSION: The proportion of DCO is positively associated with increasing age and negatively associated with HV% and the issuance of a physician's death certificate. These findings suggest that further socio-cultural efforts are required to reduce the DCO proportion. PMID- 26680832 TI - Efficacy of Pre- and Postoperative Chemotherapy in Patients with Osteosarcoma of the Extremities. AB - PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities. PMID- 26680834 TI - Epidemiology of Lung Cancer in Korea. PMID- 26680833 TI - Lung Cancer in Korea. PMID- 26680835 TI - Genetic Susceptibility to Lung Cancer in Koreans. PMID- 26680836 TI - Lung Cancer Screening with Low-Dose Spiral CT. PMID- 26680837 TI - Loss of CD10/NEP Expression in the Pulmonary Carcinogenesis. AB - PURPOSE: S: The cell surface metalloproteinase CD10/ neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. CD10/NEP has been recognized as modulating peptide mediated proliferation of lung carcinomas and the normal airway epithelium. The purposes of this study are to evaluate the expression of CD10/NEP in human lung cancers, including non- small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), and to correlate its expression with several clinicopathologic parameters, including proliferative activity. MATERIALS AND METHODS: CD10/NEP expression and proliferative activity were evaluated by immunohisto chemistry in 55 formalin-fixed and paraffin-embedded NSCLC and SCLC specimens, using anti Human CD10/ NEP and Ki-67 primary antibodies. The correlations between CD10/NEP expression and either Ki-67 proliferative activity or several clinicopathologic parameters were analyzed by chi-square test or Fisher's exact test. RESULTS: Most NSCLC (76%) and SCLC (80%) cases showed loss of CD10/NEP expression in the tumor cells, whereas the bronchial and alveolar epithelia and stromal fibroblasts in the adjacent healthy lung revealed strong expression of CD10/NEP. Its expression was not correlated with proliferative activity or any of the clinicopathologic parameters except for age. Only in terms of topographical expression was CD10/NEP expression found to be inversely correlated with Ki-67 proliferative activity. CONCLUSION: These results suggest that loss of CD10/ NEP expression may be important in the pulmonary carcinogenesis of both NSCLCs and SCLCs, which is topographically related to NSCLC proliferative activity, especially in the squamous cell type. PMID- 26680838 TI - A Phase II Study with Gemcitabine and Carboplatin in Patients with Advanced Non small Cell Lung Cancer. AB - PURPOSE: To evaluate the efficacy and safety of gemcitabine and carboplatin (GC) in the treatment of advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1999 and April 2001, 34 patients were enrolled in this study. The median age was 66 (range: 52-74) years old and all were male. Sixteen patients demonstrated stage IIIB, 15 stage IV, and 3 recurrence of disease after surgery. Twenty-two patients showed a ECOG performance status of 0 or 1 and 12 had 2. Twenty patients presented with squamous cell carcinoma, 11 adenocarcinoma and 3 unclassified NSCLC. The treatment regimen consisted of intravenous carboplatin AUC of 6 on day 1 and gemcitabine 1,250 mg/m2 on day 1 and 8. The treatment was repeated every 28 days. Toxicities were evaluated according to WHO toxicity criteria. RESULTS: All thirty-four patients were evaluable. Partia responses were observed in 15 patients. The overall response rate was 44% (95% confidence interval: 27-61%) and the median response duration was 26 (range 8-60 ) weeks. The median survival of all patients was 50 (range 8-70 ) weeks. During a total of 144 cycles, granulocytopenia greater than WHO grade 2 occurred in 2%, thrombocytopenia in 2%, and anemia in 3%, respectively. Non- hematologic toxicities were minor and easily controlled. CONCLUSION: A combination chemotherapy of intravenous gemcitabine and carboplatin has a relatively high activity with acceptable toxicities in patients with advanced NSCLC. PMID- 26680839 TI - Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: To evaluate the efficacy and toxicity of the combination therapy of paclitaxel and cisplatin in advanced, non-small cell, lung cancer patients. MATERIALS AND METHODS: Between December 1997 and September 2001, 37 patients with advanced, non-small cell, lung cancer were enrolled in this study. Patients were treated with paclitaxel (135 mg/m2, 24 hr infusion) and cisplatin (75 mg/m2). The treatments were repeated every 4 weeks. RESULTS: Among the 37 patients enrolled, 21 were treated with paclitaxel and cisplatin as a first-line and 16 patients as a second-line. The median age of the patients was 59. In the first-line group, 10 had stage IIIB and 11 had stage IV, non small cell lung cancer. Of 21 patients in first-line treatment group that could be evaluated, objective responses were observed in 6 patients (response rate: 28.6%, CR: 4.8%, PR: 23.8%). The mediansurvival duration for patients was 48 weeks. With the second-line group, 3 patients showed a partial response (response rate: 18.7%) to treatment, with median survival duration of 44 weeks. Grade 3-4 leukopenia was observed in 27.1% of the first-line, and 23.6% in second- line, treatment groups. CONCLUSION: Combination chemotherapy, with paclitaxel and cisplatin, in non-small cell lung cancer has acceptable toxicities in both first and second-line treatment groups. In terms of efficacy, no superior response was shown for either group. More randomized studies, with a larger group of patients, are required to prove the true efficacy. PMID- 26680840 TI - Clinical Significance of p53, P-glycoprotein, and Glutathione S transferase-pi in Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: A retrospective study was performed o define the clninical significance of p53, P-glycoprotein (Pgp), and Glutathione S transferase-pi (GST-pi) immunohistochemical (IHC) expression in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed fifty seven patients with advanced NSCLC who had undergone surgical resection or bronchoscopic biopsy between March 1997 and March 1999. IHC staining for p53, GST-pi, and Pgp was performed using formalin-fixed, paraffin-embedded specimens of the fifty seven patients. RESULTS: The IHC expression rate was 63% for p53, 28% for Pgp, and 53% for GST-pi, respectively. The median survival of the fifty seven patients was 45 weeks and the response rate was 38.6% (partial response, 22/57). The chemotherapy response and median survival of the p53 negative group (57% and 61 weeks) were better than those demonstrated by the p53 positive group (28% and 21 weeks) (p<0.05). Additionally, the GST-pi negative group showed a greater improvement of survival and response rate than the positive group (p<0.05). Pgp expression status appeared to have no significant differential effect on chemotherapy response and survival. CONCLUSION: These results suggest that immunohisto chemical staining of p53 and GST-pi may be useful in predicting the response to chemotherapy as well as survival in advanced NSCLC. However, this study is limited by its retrospective nature and the small numbers of tumors studied from a heterogenous group of patients. PMID- 26680841 TI - Correlation of Mast Cell Densities, Angiogenesis and Vascular Endothelial Growth Factor in Proper Muscle Gastric Carcinomas. AB - PURPOSE: There are increasing evidences that angiogenesis enhances tumor growth and biological aggressiveness in gastric carcinoma. Mast cells have been implicated in the angiogenic process, by secreting angiogenic factors including vascular endothelial growth factor (VEGF), or enzymes that degrade extracellular matrices. However, the exact nature of mast cells in relation to cancer is contradictory so we conducted retrospective studies, to find the significance of mast cell densities, and microvessel counts in each clinicopathologic factors, including VEGF expression, in proper muscle (PM) gastric carcinoma. MATERIALS AND METHODS: 52 specimens, obtained from patients with PM gastric carcinoma, were studied using the immunohistochemical methods, monoclonal antibodies for mast cell tryptase, factor VIII-related antigen and VEGF. RESULTS: Mast cell densities were significantly increased in diffuse histologic type (p=0.042), infiltrating margins (p<0.0001) and VEGF positive (p=0.010) tumors.Microvessel counts were significantly higher in patients over 55 years old (p=0.024), with tumor sizes larger than >3 cm (p=0.015), diffuse histologic type (p=0.038) and lymph node metastasis (p=0.001). Similarly there were significantly increased densities in VEGF positive tumors (p<0.0001). Pearson's correlation analysis revealed a significant relationship between mast cell densities and microvessel counts (r=0.614, p<0.01), indicating a high vascular grade with increased number of mast cells. CONCLUSION: We demonstrated a close relationship between mast cell densities, microvessel counts and VEGF expression. These results suggest that mast cells and VEGF are important regulators of tumor angiogenesis and cooperatively induce the formation of vascular stroma in PM gastric carcinomas. PMID- 26680842 TI - Telomerase Activity and Expression of hTR and TERT in Human Soft Tissue Sarcomas. AB - PURPOSE: Sarcomas have rarely been analyzed for telomerase, which is an RNA dependent DNA polymerase to maintain telomeres and prevent telomere shortening. This study was undertaken to determine telomerase activity and the expression of the telomerase subunits human telomerase RNA (hTR) and telomerase reverse transcriptase (TERT) in soft tissue sarcomas. MATERIALS AND METHODS: Twenty three sarcomas were analyzed for the telomerase activity by a radioactive PCR-based TRAP assay. All of the samples were further investigated for the expression of hTR by in situ hybridization and for TERT and p53 by immunohistochemistry. RESULTS: Telomerase activity was detected in four (17%) samples. Expression of hTR was demonstrated in 11 (48%) cases, whereas TERT was expressed in 20 (87%).Of the four telomerase-positive tumors, three were positive for both hTR and TERT, and one was positive only for TERT. p53 overexpression was observed in nine (39%) tumors. The frequency of p53 expression increased as the tumor grade advanced (p= .064). CONCLUSION: These data indicate that the reactivation of telomerase is an uncommon event in human soft tissue sarcomas. The high frequency of the expression of hTR and TERT in these tumors suggests that telomerase activity may be regulated at the transcriptional level and an additional event leading to telomerase activation exist. PMID- 26680843 TI - Expression of Cell Surface Receptors on Human Glioblastoma Xenograft Model in NOD/SCID Mouse. AB - PURPOSE: To obtain basic data for development of a glioblastoma-specific immunotoxin, the expression of variable cell surface receptors on a human glioblastoma xenograft model was evaluated, using NOD/SCID mice. MATERIALS AND METHODS: We developed a xenograft model in NOD/SCID mice implanted with a human glioblastoma cell line (U-87MG). Immunohistochemical studies were performed on implanted tumor nodules (n=8) using antibodies against CD71, EGFR, IGF-IRalpha, CXCR4 and IL-4Ralpha. RESULTS: Expression of IL-4Ralpha, in implanted tumornodules, was the highest of the cell surface receptors evaluated in this study. However, the endothelial cells in, and around, the tumor nodules also revealed immunopositivity against IL-4Ralpha. The immunoreactivity of IL-4Ralpha, and other surface receptors such as CD71, IGF-IRalpha and EGFR, was prominent in tumor nodules associated with tumor necrosis. CONCLUSION: IL-4Ralpha would be a possible target for the development of glioblastoma-specific immunotoxin, although there are limitations due to its endothelial expression. PMID- 26680844 TI - Conjunctival Lymphoma: Retrospective Analysis of the Treatment Result and Complications with Radiation Therapy. AB - PURPOSE: In order to evaluate the response to radiation therapy and to analyze the patterns of failure, survival and complications, we performed a retrospective analysis of patients with conjunctival lymphoma. MATERIALS AND METHODS: From November 1991 to March 1999, 11 patients were diagnosed as conjunctival lymphoma at Asan Medical Center. Five patients had bilateral involvements, and a total of 16 eyes received radiation therapy. Using 6 to 9 MeV electrons or 4 MV photon beams, all patients were treated with a single anterior field to total doses ranging from 30 Gy to 45 Gy delivered in 10 to 25 fractions. The median follow up period was 57 Months. RESULTS: All patients achieved a complete response with radiation therapy. Two of 16 eyes that were treated (12.5%) developed local recurrence after radiation therapy, however they were salvaged with 30 Gy of reirradiation. The five-year local control was 88.9%. One out of 11 patients (9.9%) developed lung metastasis and received chest irradiation. At the last follow up, one had died of pneumonia and 10 patients were alive without disease evidence. The five-year overall survival rate was 77.8% and 5-year disease free survival was 77.8%. Cataract and dry eye occurred in one patient (9.9%) respectively. CONCLUSION: Radiation therapy is a very effective and safe treatment modality for conjunctival lymphoma. The local control rate of radiotherapy was excellent and complications were acceptable. Radiation therapy is also an effective treatment modality for recurrent conjunctival lymphoma. It generally requires more than three months to achieve complete response following radiation therapy, thus we recommend evaluating the response to radiation therapy at three months after completion of treatment. PMID- 26680845 TI - Sclerotheraphy with OK-432 for the Treatment of Lymphangiomas. AB - PURPOSE: To evaluate the efficacy of sclerotherapy with OK-432 for lymphangiomas. MATERIALS AND METHODS: Retrospective review of twelve patients with lymphangiomas who were treated with OK-432 from 1996 to 2000. RESULTS: Twelve patients were treated by sclerotherapy with OK-432. Ten patients were received sclerotherapy with OK-432 as primary therapy, and two were treated as secondary therapy after failure of surgery. Six cases were cystic hygroma (macrocystic); all of them, complete shrinkage was obtained. The other six cases were cavernous lymphangioma (microcystic): two of them, therapy were successful, but four were failed to achieve satisfactory shrinkage. So, they underwent surgical excision after failure of sclerotherapy. The results were excellent in cystic hygroma (success rate; 100%), however moderately poor results were obtained in cavernous lymphangioma (success rate 33.3%). CONCLUSION: Intralesional injection of OK-432 is effective therapy for cystic hygroma as a primary therapy. PMID- 26680846 TI - Annual Report of the Korea Central Cancer Registry Program 2000: Based on Registered Data from 131 Hospitals. AB - PURPOSE: The Korea Central Cancer Registry (KCCR) program completed a nationwide hospital-based cancer registry to provide basic statistical data on cancer incidence. MATERIALS AND METHODS: In 2000, 131 hospitals participated in the KCCR program. All cancer registry data, which were submitted by the participating hospitals during the year, were reviewed and analyzed by the committee members. RESULTS: Of the 94,474 cases that were registered, 7,735 (8.2%) duplication cases were excluded. Of the remaining 86,739 cases, 2,893 cases (3.3%) of carcinoma in situ (morphology code/2) were excluded, leaving a final total of 83,846 cases for analysis, 48,005 (57.3%) male and 35,841 (42.7%) female. The leading age group was 60-64years (15.1%). The six leading primary cancer sites in the order of their relative frequency were the stomach (20.8%), lung (12.2%), liver (12.2%), colorectum (10.3%), breast (6.5%), and uterine cervix (4.5%). In males, the three leading primary cancer sites were the stomach (24.5%), liver (16.3%), and lung (16.3%). In females, the stomach (15.8%), breast (15.1%), and uterine cervix (10.6%). Among the 1,126 cases of childhood malignancies, leukemia (32.7%) was the most common cancer type. CONCLUSION: We report our analysis of the KCCR data from 131 nationwide hospitals during 2000. PMID- 26680848 TI - Detection of Micrometastases of Breast Cancer by Immunohistochemical Analysis of Cytokeratin. AB - PURPOSE: Axillary lymph node metastases are the single most important predictor of overall survival in patients with breast cancer. Micrometastases are defined by the American Joint Committee on Cancer as tumor foci less than or equal to 2 mm in greatest dimension. Recently, up to 30% of breast cancer patients were reported to have micrometastases. In this paper, to assess the rate of micrometastases in patients with stage I breast cancer, we attempted to determine the most useful marker of the micrometastases in node negative cases by routine histopathologic examination of regional lymph nodes and comparison of the results with the influencing factors on prognosis. MATERIALS AND METHODS: We performed immunohisto chemical staining for pancytokeratin, cytokeratin 7, cytokeratin 20 and CEA to identify which protein was the most useful marker for the detection of micrometastases in 86 node negative cases and determined the correlation between histological and clinical data. RESULTS: A total of 5 lymph nodes in 5 separate cases showed micrometastases among the total 1,296 lymph nodes and 86 cases. The rates of micrometastases of lymph nodes and cases were 0.38% and 5.8%, respectively. The tumor type of micrometastasis was infiltrating ductal carcinoma in all cases. None of the microme tastases cases showed any relationship with tumor grade, tumor size, expression of ER and PR, patient survival rate or recurrence rate. The most useful marker to detect micrometastases was pancytokeratin. CONCLUSION: The results of this study indicate that micrometastasis of axillary lymph nodes does not carry any independent prognostic significance. PMID- 26680847 TI - Retrospective Analysis of the Results of Adjuvant Chemotherapy in Breast Cancer Patients with 10 or More Positive Nodes: Nonrandomized Comparison of Adriamycin Containing Regimens. AB - PURPOSE: To evaluate the results of adriamycin-based adjuvant chemotherapy with or without high dose chemotherapy (HDC) with stem cell transplantation (SCT) in breast cancer with 10 or more positive axillary nodes. MATERIALS AND METHODS: Seventy-one breast cancer patients who had undergone surgery and had 10 or more positive axillary nodes were included in this study held between January 1997 and December 1999. The pathologic and clinical records were reviewed retrospectively. RESULTS: Twenty-nine patients were treated with adriamycin followed by 8 courses of CMF (group I); 22 patients received 4 courses of adriamycin and 7 patients received 3 courses of adriamycin. Twenty-six patients received median 6 courses of CAF (group II) and 16 patients underwent HDC and autologous SCT (group III). With a median follow-up of 27.1 months, relapses were observed in 24 patients (33.8%) and the 3-year disease-free survival (DFS) rate was 57.1%; group I/II 55.4%, and group III 62.7%. The three-year overall survival (OS) rate was 86.1%; group I/II 83.0%, group III 93.8%. There were no difference in the 3-year DFSs or in the OSs of group I and group II. However, patients who received only 3 courses of the sequential adriamycin in group I showed a significantly poorer 3-year OS than those that received 4 courses of adriamycin (42.9% vs. 95.5%). CONCLUSION: Our study shows that adriamycin-containing combination chemotherapy is as effective as HDC with SCT in patients with 10 or more positive axillary lymph nodes judging by 3-year DFS and OS, and shows that three courses of adriamycin seems to be inadequate. PMID- 26680849 TI - Development and Test of an Information Needs Scale for Outpatients Undergoing Chemotherapy. AB - PURPOSE: The purpose of this study was to develop and test an Information Needs Scale for Korean outpatients undergoing chemotherapy (INS-C). MATERIALS AND METHODS: Thirty-three items of the INS-C had content validity based upon findings in the literature and the experiences of expert oncology physicians and nurses. Each item consisted of a five-point Likert scale from 1 (don't want to know) to 5 (want to know very much). The items were administered to 175 Korean outpatients undergoing chemotherapy. The data obtained was analysed using a factor analysis for construct validity and Cronabch's alpha for internal consistent reliability. RESULTS: From the factor analysis, six subscales were derived significantly. The six subscales explained 64.62% of the variance. The subscales were named Side Effects/Investigative Tests (9 items), Spread of Disease (4 items), Financial Cost (2 items), Treatment (7 items), Activities/ Eating (6 items), and Interrelationships/Support (5 items). The Cronbach's alpha of the total INS-C was .95, and the alpha of the subscales ranged from .77 to .91. CONCLUSION: The present study suggests that the INS-C is a reliable and valid instrument to measure the information needs of outpatients undergoing chemotherapy. Health professionals caring for patients with cancer should assess the informational needs of their patients using a reliable and valid instrument and be prepared to provide accurate information. PMID- 26680850 TI - Dietary Habit and Helicobacter pylori Infection in Early Gastric Cancer Patient. AB - PURPOSE: Helicobacter pylori (H. pylori) is now generally accepted to be strongly associated with the development of gastric cancer, as well as intakes of some salted foods, charred foods, etc. To evaluate the association among dietary habits, H. pylori infection, and early gastric cancer in Koreans, a hospital based case-control study was conducted. MATERIAL AND METHOD: A total of 268 persons participated in this case-control study. Sixty nine patients were newly diagnosed as an early gastric cancer (EGC) at the Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, Seoul, Korea. One hundred ninety-nine subjects with no symptoms who visited the Health Promotion Center for their general checkups were selected as the controls. All subjects were examined for H. pylori infection, biochemical blood test the life style, and dietary habit were interviewed by a trained dietition with semi-quantitative food frequency question naire (FFQ) and adaptive salt concentration were taste evaluated. RESULTS: H. pylori seropositivity was observed in 88.4% in cases, as compared with 74.9% in controls (OR=2.5, 95% CI: 1.1-5.7). The adaptive salt concentration was associated with early gastric cancer risk (chi-squir=50.8, p<0.001). The analysis of food intake frequency demonstrated that early gastric cancer risk was reduced by the intake of clear soups, raw vegetables, fruits and juices, beef with vegetables and soybean curds. On the other hand, high intake of salt fermented fish and kimchi elevated the risk of early gastric cancer. CONCLUSION: These results suggest that some dietary factors and H. pylori infection have a significant association with the development of early gastric cancer. PMID- 26680851 TI - Phase II Trial of Gemcitabine, UFT-E, Leucovorin Combination Chemotherapy in Advanced Pancreatic Adenocarcinoma. AB - PURPOSE: To evaluate the efficacy and toxicity of a Gemcitabine, UFT-E, Leucovorin combination chemotherapy in the treatment of advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients <=70 years, with no prior chemotherapy and with bidimensionally measurable advanced pancreatic adenocarcinoma, ECOG performance status <=2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or a Karnofsky performance status between 50 and 70. Treatment consisted of 1,000 mg/m2 of Gemcitabine on days 1, 8 and 15, repeated every 4 weeks, with UFT-E administered orally 500 mg-700 mg by body surface area (BSA). Leucovorin was administered 45 mg/day orally. Dosages of UFT-E and Leucovorin were divided and administered three times per day from day 1 to day 21. After 7 days of rest, UFT-E and Leucovorin were administered repeatedly. RESULTS: Twenty-three patients were enrolled between April 1999 to April 2000. Eighty two cycles (median, four cycles) were delivered to all patients. The objective response rate was 15.8% in 19 assessable patients and 13.0% in the intent-to-treat population. Twelve patients (57.9%) displayed stable disease. Grade 3 or 4 neutropenia occurred in 30.4% of patients, nausea/vomiting in 8.3%, diarrhea in 4.3%, and mucositis in 4.3%. The median time to progression was 8 months. The median survival was 8 months in the assessable population and 6 months in the intent-to-treat population Clinical benefit was achieved in 11 (57.9%) of 19 assessable patients. CONCLUSION: Gemcitabine, UFT-E, Leucovorin combination chemotherapy is a well-tolerated and safe regimen in cases of advanced pancreatic adenocarcinoma. Although the response rate is low, it shows a survival benefit and clinical benefit and deserves further evaluation in a phase III trial. PMID- 26680852 TI - Immunohistochemical Study of beta-catenin Expression between Hepatocellular Carcinoma and Cholangiocarcinoma. AB - PURPOSE: beta-catenin is an intracellular protein that is an integral component of the cadherin-mediated cell-cell interaction and a downstream transcriptional activator in the wnt signal transduction pathway. Inappropriate activation of beta-catenin has recently been implicated in the development of hepatocellular carcinoma and cholangiocarcinoma. Nuclear beta-catenin expression is strongly associated with gene mutation. This study was designed to evaluate the pattern of beta-catenin expression between hepatocellular carcinoma and cholangiocarcinoma. MATERIALS AND METHODS: Immunohistochemical expression of beta-catenin was studied in 7 normal livers, 33 hepatocellular carcinomas and 20 cholangiocarcinomas, that were formalin fixed and paraffin embedded. RESULTS: beta-catenin was expressed mainly in the cytoplasmic membrane of the normal hepatocytes and bile ducts. Nuclear expressions, not noted in the normal liver, were noted in 30% of the hepatocellular carcinomas and 10% of the cholangiocarcinomas. And, nuclear expression was more common in the high grade (50%) hepatocellular carcinomas than the low grade (18%) hepatocellular carcinomas (p<=0.05). CONCLUSION: The above results indicate that nuclear expression of beta-catenin is observed in the carcinoma but not the normal liver, and is associated with high grade liver carcinoma. PMID- 26680853 TI - The Effects of Insulin-like Growth Factor-I (IGF-I) in Mouse Lung Cancer Cells. AB - PURPOSE: Insulin-like growth factor-I (IGF-I) is an important mitogen in many types of malignancies. The purpose of this study was to evaluate the role of the IGF system on cell proliferation and cell death in mouse lung cancer cell lines (3LL). MATERIALS AND METHODS: Northern analysis was performed in 3LL cells. We evaluated the phosphorylation of IGF-I receptor (IGF-IR) with IGF-I stimulation. MTT assay was performed after treating 3LL cells with IGF-I and the treatment effect on cell death in the presence of anticancer drug was investigated. RESULTS: Northern analysis revealed the presence of IGF-I and IGF-IR mRNA expression in 3LL cells. IGF-I increased cellular proliferation in serum free media. IGF-I also stimulated the tyrosine phosphorylation of two proteins: one, with a molecular mass of 95 kDa, was the beta-subunit of IGF-IR; the other, with an approximate molecular mass of 185 kDa, was originally identified as the insulin receptor substrate-I (IRS-I). IGF-I at a low concentration inhibited the cell death induced by adriamycin. CONCLUSION: IGF-I, a mitogen through the phosphorylation of the IGF-IR beta-subunit, acts as a survival factor to inhibit cell death. Therefore, these findings suggest that IGF-I and IGF-IR are involved in both the cell proliferation and cell death associated with cancer cell growth. PMID- 26680854 TI - 5-FU Induces Apoptosis of Fas (+), HepG2 Cells Via Activation of Fas-mediated Caspase and Mitochondria Dysfunction. AB - PURPOSE: In order to investigate the role of Fas on the chemosensitivity of cancer cells in regards to chemotherapeutic agents, the Fas/FasL signaling pathway of apoptosis was explored in human hepatoma cells. MATERIALS AND METHODS: Fas expression of hepatoma cells including Chang, Huh7, HepG2, and Hep3B cells, was determined by RT-PCR and flow cytometry analysis. Cell viability was measured by MTT assay and apoptosis was assessed by DNA fragmentation assay. The catalytic activity of the caspase-family proteases including caspase-3, 6, 8, and 9 proteases, was tested using fluorogenic biosubstrates. The expression of apoptotic mediators including cytochrome c, PARP, and Bcl2 family proteins were measured from cytosolic and mitochondrial compartments. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. RESULTS: Fas mRNA was constitutively expressed in Chang and HepG2 as defined as Fas (+) cells, but not in Huh7 and Hep3B cells, defined as Fas (-) cells. Fas (+) cells were markedly sensitive to 5-FU whereas Fas (-) cells were resistant and able to survive. 5-FU increased Fas expression of Fas (+) HepG2 cells and simultaneously resulted in apoptotic death, characterized by the ladder-pattern fragmentation of genomic DNA. Moreover, it increased the catalytic activity of caspase-8 protease, which eventually cleaved the Bid into truncated Bid which translocated into mitochondria only in Fas (+) cells. It also increased the caspase-9 protease activity with Bax expression, cytosolic release of cytochrome c, and mytochondrial dysfunction only in Fas (+) HepG2 cells. Furthermore, 5-FU increased the enzymatic activity of caspase-3 protease with PARP digestion in HepG2 cells. CONCLUSION: 5-FU exerted cytotoxicity against hepatoma cells via activation of Fas-mediated apoptotic signaling including caspase cascades and mytochondrial dysfunction. Our data suggests that Fas may be an important modulator of the chemosensitivity of cancer cells vis- -vis anticancer chemotherapeutic agents. PMID- 26680855 TI - Treatment Results of Postoperative Radiation Therapy for Malignant and Atypical Meningioma. AB - PURPOSE: We evaluated the survival rate, prognostic factors and patterns of failure in malignant and atypical meningiomas, and investigated the role of radiation therapy in the treatment of these tumors. MATERIALS AND METHODS: We retrospectively reviewed nineteen patients treated at Asan Medical Center between Mar. 1994 and Jun. 2000 with histologically confirmed malignant or atypical meningiomas. The median patient age was 52 years. The extent of surgery prior to radiation was gross total resection in 13 and subtotal resection in 6. Eleven patients were referred for radiation immediately after diagnosis and the remainder after at least one recurrence. All patients received megavoltage radiation to a median dose of 55.8 Gy. The median follow-up period was 41 months. RESULTS: Eleven patients (57.9%) showed no evidence of disease, five patients died of meningioma and three were alive with disease. The 5-year overall and relapse-free survivals were 75.9 and 50.6%, respectively. There were no statistically significant prognostic factors found to be associated with relapse free survival by univariate or multivariate analysis. During the follow-up period, no significant treatment-related complications were detected. CONCLUSION: The major patterns of failure were in-field recurrence. In order to reduce local failure, a higher radiation dose may be needed and a high precision therapy should be considered. PMID- 26680856 TI - MINE (mesna, ifosfamide, mitoxantrone, etoposide) Chemotherapy as a Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma. AB - PURPOSE: The prognosis of non-Hodgkin's lymphoma (NHL) is disappointing for patients who experience primary treatment failure or relapse after an initial response. Patients in relapse may respond again to chemotherapy, however the time to disease progression becomes shorter and eventually the disease becomes resistant. The aim of this study was to evaluate the efficacy and safety of the MINE regimen in the treatment of patients with relapsed or refractory NHL. MATERIAL AND METHODS: Forty-three pretreated patients with a median age of 56 years were enrolled into the study between October 1995 and June 2000. Most patients (60.5%) had a performance status of 0 to 1, and a diffuse large cell subtype (55.8%). Seventy-four percent of patients had stage III or IV disease at the start of MINE treatment. Eighteen (41.9%) patients had complete response, 5 (11.6%) had partial response, and 20 (46.5%) had failed to respond to prior therapy. Ifosfamide 4 g/m2 was divided over 3 days and administered IV over a 1 hour period. Mitoxantrone 8 mg/m2 was administered as a short IV infusion on day 1. Etoposide (65 mg/m2/day) was infused over 1 hour on days 1 to 3. A total of 144 cycles was administered, with a mean of 3.34 cycles per patient (range, 1-8). The mean relative dose intensity was 87.4%. RESULTS: 1) Nine patients achieved a complete response and nine patients achieved a partial response, resulting in an overall response rate of 43.8% of the 41 assessable patients. 2) The median survival time was 6 months (95% CI, 4 to 8 months), and the median time to failure was 5 months (95% CI, 3 to 7 months). 3) A statistically significant association with complete response rates was found for complete response to prior therapy (p=0.049). The significant factors for overall survival were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.012, respectively). The significant factors for time to treatment failure were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.044, respectively). 4) The main result of toxicity of MINE was bone marrow suppression. CONCLUSION: The response to MINE chemotherapy and serum 2 microglobulin were both independent prognostic factors for overall survival and time to treatment failure. As the median time to treatment failure for complete responses was 14 months, the best use of this regimen could be in a strategy that includes prompt consolidation of a complete response with intense chemotherapy, with or without hematopoietic stem cell rescue. PMID- 26680857 TI - Gastrosplenic Fistula Complicated in a Patient with Non- Hodgkin's Lymphoma. AB - Reported cases of gastrosplenic fistulas are extremely rare in the literature. Malignancy is the primary cause in 50% of patients, followed by perforated peptic ulcer (40%). Fistulas can cause spleen rupture and potential bleeding that threaten the life of the patient. Lymphoma is the most common cause of malignancy complicated with gastrosplenic fistula. Most gastrosplenic fistulae caused by lymphoma eventually close following chemotherapy, although splenectomy should be performed to avoid further complications. We experienced a case of non-Hodgkin's lymphoma complicated with gastrosplenic fistula in a 21 year-old man. He was admitted to our hospital because of LUQ mass. On the abdominal CT, a splenic mass with central necrosis and gas was discovered. The biopsy specimen of the stomach and spleen displayed diffuse, large B cell type non-Hodgkin's lymphoma. After one cycle of CHOP chemotherapy, the LUQ mass was markedly regressed although the gastrosplenic fistula was still present on the follow-up CT. The fistula was treated by splenectomy and a partial resection of gastric fundus. Follow-up chemotherapy was continued after surgery. PMID- 26680858 TI - Randomized Controlled Open Labelled, Phase III Trials, Comparing the Efficacy between Fentas(R) and Durogesic(R) Patches in Controlling Cancer Pain: Multicenter Trial. AB - PURPOSE: Fentanyl is a synthetic opioid and transdermal therapeutic system (TTS), designed to release the drug into the skin at a constant rate, ranging from 25 to 100 microgram/hr, for up to 3 days. For the control of chronic cancer pain, Durogesic(R) patches (Janssen Co., USA) are now widely used. Recently, the Hana Company in Korea developed a new fentanyl patch, Fentas(R) using a different method. To compare the efficacy, and safety, of the fentanyl patch manufactured in Korea (Hana Pharm. Co. Ltd), with the Durogesic(R) patch, in controlling cancer pain, we performed randomized controlled, open labelled, phase III studies. MATERIALS AND METGODS: From January 2000 to April 2001, 85 patients were enrolled, 69 of whom (42 in D arm and 43 in F arm) completed the study, and were therefore assessable for per protocol (PP) analyses. RESULTS: There were no significant differences between the two groups in baseline characteristics, with the exception of age. The primary end point was to show the therapeutic equivalence of the two patches. In these clinical trials, the confidence interval of difference, between the test drug (Fentas(R)) and the control (Durogesic(R)), was 0.027~ +0.124 by intention to treat (ITT) analysis. Even if the upper confidence interval exceeds + 0.1, the test drug is not superior to the control drug, because the confidence interval includes 0. However, by PP analysis, the confidence interval lies exactly within +/- 0.1. Therefore, we could conclude the two patches are therapeutically equivalent. The second endpoint was the difference of visual analog scale (VAS) between the baseline and the average of three measurements after treatment. The difference in VAS was 50.44+/-10.28 for the F arm, and 44.69+/-11.00 for the D arm. By PP analysis the test drug was superior to the control (p=0.028). The rescue morphine amount was 81.21+/-124.76 for F arm and 66.19+/-115.9 for D arm, and there was no significant difference between the two groups (p=0.6063). The most common adverse effects of both fentanyl patches were nausea or vomiting (55.3%), somnolence (50.0%), constipation (39.5%), gastrointestinal discomfort (57.9%) and headaches (25.0%). In general there was no significant difference in side effects or laboratory data between the two groups. CONCLUSION: These findings suggest that Fentas(R) patches, administered every 3 days, are effective, safe, and well tolerated for the treatment of most patients with cancer pain and is as effective or better than Durogesic(R). PMID- 26680859 TI - Immunohistochemical Study for CD44v6 in Hepatocellular Carcinoma and Cholangiocarcinoma. AB - PURPOSE: CD44 is a multifunctional adhesion molecule in cell-to-cell and cell-to matrix interactions. This transmembrane glycoprotein exists in either standard or variant form, with the variation originating in alternative splicing. This study was designed to evaluate the role of CD44v6, one of the CD44 isoforms, in hepatocellular carcinoma and cholangiocarcinoma. MATERIALS AND METGODS: Immunohistochemical expression of CD44v6 was studied in 7 normal livers, 14 hepatocellular carcinomas and 16 cholangiocarcinomas, that were formalin fixed and paraffin embedded. RESULTS: CD44v6 was frequently expressed in the normal hepatocytes and hepatocellular carcinomas. Expression was not noted in the normal bile duct within the portal tract. CD44v6 was positively expressed in some of the proliferating bile ducts (43%) and cholangiocarcinomas (69%). CONCLUSION: CD44v6 expression may be more important in the stepwise carcinogenesis of the bile duct than in the normal hepatocyte, but further study is needed. PMID- 26680860 TI - Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization. AB - PURPOSE: There have only been a few cytogenetic studies of hepatocellular carcinoma (HCC), and so far, no consistent specific chromosomal abnormalities have been described. Here, we have used comparative genomic hybridization (CGH), a powerful molecular cytogenetic technique for detecting changes of the copy number throughout the genome, to screen for genetic alterations in HCC cell lines. The CGH results were compared with those derived from G-banding and chromosome painting. MATERIALS AND METGODS: Conventional cytogenetic analyses were performed on five HCC cell lines, SNU-354, SNU-368, SNU-387, SNU-449 and SNU 475, using a G- banding staining technique. In CGH, equal amounts of differently labeled DNA from the cell lines, and normal reference DNA, were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities quantified separately as gray levels along the single chromosomes. The over- and under-represented DNA segments were determined by computation of ratio images and average ratio profiles. To confirm the CGH results, florescence in situ hybridization (FISH), with chromosome specific painting, was performed using indirectly labeled chromosome specific paints. RESULTS: Complex unbalanced chromosomal aberrations, which could not be identified reliably by conventional cytogenetics in HCC cell lines, were successfully resolved by CGH analysis. CGH results were validated using FISH with chromosome specific probes. In HCC cell lines, gains in DNA copy number were more common than losses. The most prominent changes were gains of 1q12- qter (80% of cases), 1q41-qter (100%), 7 (80%), 8q12-qter (60%), 8q23-qter (80%) and 20q12 qter (60%). Recurrent losses were mapped on 4q13-qter (60%), 16q12-qter (60%), 16q21-qter (80%), 13q12-q14.2 (60%) and Yq11.2 (100%). All four male HCC cell lines showed loss or rearrangement of the Y chromosome. CONCLUSION: Conventional cytogenetics, CGH and FISH using painting probes, represent complementary approaches that, when employed in combination, could greatly facilitate the comprehensive analysis of chromosomal imbalances in HCC cell lines. Our results suggest the existence of an oncogene, or protooncogenes, on chromosome 1q41-qter, and the tumor suppressor genes on Yq11.2, that play a role in the development and/or progression of hepatocellular carcinogenesis. PMID- 26680861 TI - Impact of Neoadjuvant Chemotherapy on Postoperative Morbidity in Locally Advanced Cervical Carcinoma. AB - PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NACT) does not increase morbidity in patients undergoing radical hysterectomy with lymphadenectomy for locally advanced cervical cancer. MATERIALS AND METGODS: A retrospective study was undertaken of 140 patients with locally advanced cervical cancer (FIGO stage Ia to IIb) who underwent radical hysterectomy with lymphadenectomy by the same surgeon at the same hospital. Among the 140 patients, 39 received NACT followed by radical hysterectomy with pelvic lymphadenectomy (NACT group). This group received three cycles consisting of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil 1000 mg/m2/day from day 1 to 5. The NACT group was compared, in terms of intraoperative morbidity and postoperative morbidity, with the other 101 patients who underwent radical hysterectomy with lymphadenectomy but without chemotherapy (surgery-only group). RESULTS: There were no significant differences in mean age, body weight or height between the two groups. The only significant difference was that the NACT patients had higher stages of cancer. The incidence of intraoperative morbidity did not differ between the NACT and surgery only patients. We considered the operation duration, amount of blood loss and need for transfusion as indicators of intraoperative morbidity. We could not find any significant differences in the duration of suprapubic catheterization, days of hemovac drainage, amount of drained hemovac fluid, days of hospitalization or postoperative febrile morbidity between the NACT and surgery-only groups. Patients in the surgery-only group had more postoperative complications (ureteral obstruction, intestinal obstruction, lymphocyst, lymphedema, and death) than the NACT group, although not to a statistically significant degree (P>0.05). CONCLUSION: In this retrospective review, there was no evidence that NACT increased intraoperative or postoperative morbidity in patients with locally advanced cervical cancer. As this was a retrospective study, other prospective, randomized studies are needed to confirm these results. PMID- 26680862 TI - Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of the Uterine Cervix Preliminary Results of Phases III Prospective Randomized Trial. AB - PURPOSE: A prospective, randomized phase III, clinical trial was performed to assess treatment related acute toxicity, early response and survival difference, between a monthly 5-FU cisplatin, and a weekly cisplatin group alone, for concurrent chemoradiotherapy in the locally advanced uterine cervical carcinoma patients. MATERIALS AND METGODS: Between March 1998 and March 2000, 35 patients, with locally advanced (FIGO stage IIB to IVA) cervical carcinoma, were studied, but 5 patients were excluded inform the analysis due to their refusal of treatment. The patients were randomly assigned to 'monthly 5-FU cisplatin' (arm I), or 'weekly cisplatin' (arm II), groups. The patients of arm I received 5-FU cisplatin (5-FU 1,000 mg/m2/day cisplatin 20 mg/m2/day, IV continuous infusion, for 5 days, 3 cycles with 4-week intervals) with radiation therapy. Those of arm II received only cisplatin (cisplatin 30 mg/m2/day, IV bolus, 6 cycles with 1 week intervals) with radiation therapy. The radiation therapy consisted of external beam irradiation of 41.4~50.4 Gy/23~28 fractions, and high dose rate intracavitary treatments, delivering a dose of 30~35 Gy to point A in 6~7 fractions. During intracavitary radiation, a parametrial boost was delivered for a point B dose of 60 Gy in the non-thickened side, and 65 Gy in the thickened side. Treatment related acute toxicities were assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. The response to treatment, and survival, were analyzed. The median follow-up period was 19 months. RESULTS: The FIGO stage distributions of arm I (n=16) and arm II (n=14) were as follows; IIB 10, IIIA 1, IIIB 4, IVA 1 in arm I, 12, 0, 1 and 1 in arm II respectively. The compliance of both arms were 80.0% and 93.3%, respectively (p=0.37). During radiation therapy, the incidences of leukopenia, greater than RTOG grade 2, were 25.0%, 14.3%, respectively. There were no patients with gastrointestinal or genitourinary toxicity greater than RTOG grade 2. The complete response rates at 3 months, following radiation therapy, were 87.5% and 92.9% respectively. Two-year disease free survival rates were 81.3%, 85.7%, respectively, for each arms. CONCLUSION: There was no significant difference in response to treatment, or patterns of failure, between the monthly FP and weekly cisplatin arms. Although there were no statistically significant differences, the patients of the weekly cisplatin arm had better compliance. More patients, and a longer follow up, are needed for improved evaluation of the regimen. PMID- 26680863 TI - Polyamines Regulate Growth Factor-Induced Protein Phosphorylation in MCF-7 Human Breast Cancer Cells. AB - PURPOSE: Growth factors stimulate protein phosphorylation resulting in transmission of mitogenic signals. In breast cancer, protein kinases and their substrate proteins are importnat in cell proliferation and phathogenesis. Polymine is known as a mediator of stimuli-induced proliferation in many cell systems. In the present study, we report the importance of polyamines in protein phosphorylation in MCF-7 human breast cancer cells. MATERIALS AND METGODS: Protein phosphorylation study was done by incubating cells in the DMEM containing [gamma-(32)P]-ATP. Quantitation of phosphorylation was analysed by fluorescene image analyzer. Tyrosine phosphorylation was detected by anti-phosphotyrosine antibody. Shc was detected by radioimmunoprecipitation and Western blotting. RESULTS: E2, TGF-alpha, and EGF enhanced the protein phosphorylation in very similar pattern. Among those proteins, 67 kDa protein was most strongly phosphorylated. But the most prominent tyrosine phosphoprotein was 52 kDa protein. DFMO at 5 mM strongly inhibited the phosphorylation of the most proteins. Externally added polyamine could recover the inhibitory effect of DFMO in protein phosphorylation. Among the 5 major tyrosine phosphoproteins, 52 and 46 kDa proteins appeared to be Shc proteins. CONCLUSION: Polyamines modulate signal transduction in relation with estrogen receptor and EGF receptor through multiple steps of protein phosphorylations. Tyrosine phosphorylation of Shc proteins were most significantly influenced by polyamines in growth factor-stimulate breast cancer cell proliferation. PMID- 26680864 TI - Glutathione S-transferase P1 Genetic Polymorphisms and Breast Cancer Risk. AB - PURPOSE: To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted in South Korea. MATERIALS AND METGODS: The study population consisted of 171 histologically confirmed incidents of breast cancer cases, and 171 age-matched controls with no present, or previous, history of cancer. A PCR method was used for the genotyping analyses, and statistical evaluation was performed by an unconditional logistic regression model. RESULTS: No association was observed in the study subjects, or the premenopausal women group with GSTP1 Val allele. However, postmenopausal women with GSTP1 Val allele had a reduced risk of breast cancer (OR=0.3, 95% CI=0.1~0.7). When the data were stratified, by the known risk factors of breast cancer, a significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); women with GSTP1 Val allele, that drank regularly, had a 3.0-fold increased risk of breast cancer (95% CI=1.1~7.9), whereas women with GSTP1 Val allele, that never drink, had protective effects (OR=0.4, 95% CI=0.2~0.8). CONCLUSION: Our findings suggest that GSTP1 Ile105Val polymorphism influences the individual susceptibility to breast cancer, and that this effect may be modified by alcohol consumption. PMID- 26680865 TI - Retinoic Acid Enhances Drug-Induced Cell Death in Anticancer Drug-Resistant Cell Lines. AB - PURPOSE: Retinoids (RA), a group of vitamin A derivatives, is known to be important for regulation of normal cellular growth and differentiation. RA treatment of various cancers resulted in cell growth inhibition and apoptosis. Therefore, the chemotherapeutic and chemopreventative activities of various types of tumor have been examined. Biological actions of RA are mediated through nuclear receptors, including the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In this study, we examined the effect of all-trans-retinoic acid (atRA) as an anticancer drug-sensitiser in cancer cell lines and in its drug resistant cancer cell lines MATERIALS AND METGODS: Cells were maintained by RPMI 1640 medium containing 10% fetal bovine serum. Cells were treated with 1 micro M atRA for 48 h, then with the desired concentration of anticancer drug for 24 h. Cell viability was measured spectrophotometrically at 540 nm using the MTT [3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Western blot analyses were performed with the desired antibodies. RESULTS: We investigated if pre-treatment with atRA enhanced the drug-sensitivity of various cancer cell lines to either 5-fluorouracil, adriamycin, or cisplatin. 5-FU (SNU638-F2) and CDDP-resistant cell (SNU638-Cis) lines, from a Korean gastric cancer cell line (SNU638) and the ADR-resistant cells (AD600) was established from a colon cancer cell line (SW620). Treatment of each cell line, with 1 micro M atRA, prior to drug exposure resulted in enhanced cell death in these cell lines. Furthermore, the effect of atRA on growth inhibition, in each drug-resistant cell line, was more obvious than in their parent cell lines. Increased activity of Transglutaminase II (TgaseII) and cleavage of Poly (ADP-ribose) polymerase (PARP) were also observed (western blot analysis. CONCLUSION: Based on our data, we suggest that atRA enhances anticancer drug-induced cell death and reverses the drug-sensitivity of the drug-resistant cancer cell lines. PMID- 26680866 TI - A Phase II Study of Oxaliplatin Combined with 5-Fluorouracil and Leucovorin (Mayo Clinic Regimen) in 5-Fluorouracil Refractory Colorectal Cancer. AB - PURPOSE: There are few therapeutic options in patients with colorectal cancer that have progressed or recurred following 5-fluorouracil (5-FU) based therapy. We evaluated the efficacy and toxicity of oxaliplatin, 5-FU, leucovorin (Mayo clinic regimen) in 5-FU pretreated advanced colorectal cancer patients. MATERIALS AND METGODS: Twenty-eight patients were enrolled in this study between January 1999 and May 2001. Patients were treated with oxaliplatin 150 mg/m2 on day 1 as a 2-hr infusion and 5-FU 425 mg/m2, leucovorin 20 mg/m2, bolus for 5 days. Treatment courses were repeated in 4-week intervals. RESULTS: The objective response rate was 25% for 28 assessable patients, all cases registered a partial response. Eleven patients (39%) demonstrated stable disease, and ten (36%) progressed. The median response duration was 5.5 months, and the median time to progression was 6.3 months. The median overall survival time was 13.5 months from the start of the chemotherapy. From the 120 cycles analyzed, grade 3,4 hematologic toxicities included neutropenia: 1.6%, and thrombocytopenia: 1.6%. The frequent grade 3.4 non-hematologic adverse reactions were nausea/vomiting (25.0%), diarrhea (14.3%), stomititis (3.6%), and neuropathy (3.6%). There were no treatment-related deaths. CONCLUSION: This phase II study had relatively higher toxicity than previous studies, and did not show an increased significant response rate. These high levels of toxicity suggest that the study treatment combination of oxaliplatin with a full dose Mayo clinic regimen arm is no feasible. Therefore, this regimen will be discontinued and a safer regimen will be adopted. PMID- 26680867 TI - Changes of Telomerase Activity and Proliferation by Inhibition of Reverse Transcriptase Activity in Human Cancer Cell. AB - PURPOSE: Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line. MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment. RESULTS: We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP. CONCLUSION: The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP. PMID- 26680868 TI - Cytogenetic Study in Suspicious Cases of Malignant Pleural Effusion. AB - PURPOSE: This study was performed to detect malignant cells in suspicious cases of malignant pleural effusion by cytogenetic analysis. MATERIALS AND METGODS: Eleven cases with pleural effusion were included in this study. Cells in pleural effusion were treated by direct, or short term, culture to prepare chromosomes. To analyze chromosomes, the G-banding method was used. RESULTS: Chromosome preparations succeeded in 10 cases. 5 cases had normal karyotypes, but in 2 of these cases malignant cells were detected on cytological examination. The other 5 cases had abnormal chromosomes, but on cytological examination showed normal cell appearances. CONCLUSION: Cytogenetic analysis of pleural effusions is not used routinely, but is more sensitive than the cytological examination of malignant pleural effusions. So, chromosome analysis is a good diagnostic tool, when chromosomal abnormalities are detected in an effusion. If a combination of cytology and cytogenetic study are used, the chance of detecting malignant cells in pleural effusion will be higher, and then more invasive diagnostic procedures, such as thoracoscopy or thoracotomy, could be avoided. PMID- 26680869 TI - Invasive Ductal Carcinoma of the Male Breast: A Case Report and Review of the Literature. AB - Breast carcinomas are an uncommon neoplastic condition in men, accounting for only 1% of all breast cancers, and less than 1% of all malignancies in men. A 70 year-old man who presented a right breast mass was found to have infiltrating ductal carcinoma. We herein report the case with a review of the literature. PMID- 26680870 TI - Analysis of Local Recurrence Following Proximal Gastrectomy in Patients with Upper Third Gastric Cancer. AB - PURPOSE: Little is known about local recurrence following proximal gastrectomy in patients with upper third gastric cancer. We performed this study to evaluate the long-term results of a proximal gastrectomy, and to analyze the risk factors of local recurrence affecting survival in these patients. MATERIALS AND METHODS: We undertook a retrospective study of 63 patients who underwent potentially curative proximal gastrectomy between 1990 and 1999, with special reference to local recurrence. RESULTS: During a median follow-up period of 37 months, 25 of the 63 patients (39.7%) developed a recurrence of cancer, with local recurrence in 15 patients (23.8%), the majority of these occurring at the remnant stomach or anastomosis. The median time to local recurrence was 38 months (8~78 months). Univariate analysis of risk factors for local recurrence revealed an infiltrative or diffuse gross type, with a tumor sizes>5 cm, a distal resection margin 0.5 uM) decreased the viability of HL-60 cells in a dose-dependent manner, which was revealed as apoptosis shown chromatin condensation and ladder pattern DNA fragmentation. As2O3 increased the catalytic activity of caspase family cysteine proteases including caspase-3 and -9 proteases. Consistently, PARP, an intracellular biosubstrate of caspase-3 protease, was cleaved from 116 kDa to 85 kDa fragments. It also induced the change of mitochondrial membrane potential. Morever, As2O3 resulted in the increase of Bak. CONCLUSION: These data suggest that As2O3 induces apoptosis of HL-60 cells through activation of intrinsic caspase protease with mitochondrial dysfunction. PMID- 26680880 TI - Suppression of Peritoneal Metastases by Expression of Murine Endostatin cDNA. AB - PURPOSE: Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases. MATERIALS AND METHODS: We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally. RESULTS: We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group. CONCLUSION: These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases. PMID- 26680882 TI - Survival of Korean Cancer Patients Diagnosed in 1995. AB - PURPOSE: To produce the nationwide 5-year survival rates of Korean cancer patients by primary cancer site. MATERIALS AND METHODS: The study subjects were cancer patients diagnosed in 1995, as documented by the Korea Central Cancer Registry (KCCR) Program. This data was collected in 120 (93%) of 129 nationwide intern- and resident-training hospitals and 75 (94%) of the 80 Korean university hospitals. Follow-up was performed by obtaining information upon vital status (i.e., whether living or dead) from the government administered whole population files. Cumulative observed survival rate (OSR) was calculated by using the life table method and the relative survival rate (RSR) was computed using the life time table for the years 1995, 1997, and 1999. RESULTS: Of the 55,042 study subjects, the OSR for all Korean cancer patients was 61.4% at 1 year and 38.1% at 5 years. The RSR for all cancers was 62.5% at 1 year and 41.4% at 5 years, and the 5-year RSRs for all cancers in men and women were 32.6% and 53.2%, respectively. CONCLUSION: This is the first nationwide report upon 5-year cancer survival by primary site in Korea. Men showed a lower survival rate than women in most malignancies. Pancreatic and thyroid cancer had the lowest and highest 5 year survival rates, respectively. PMID- 26680883 TI - The Effect of Intensified Induction Using Vanderbilt Regimen in Patients with an Intermediate Grade Non-Hodgkin's Lymphoma Having 2 or 3 Adverse Factors on the Age-adjusted International Prognostic Index. AB - PURPOSE: The purpose of our study was to evaluate the outcome of intensified induction therapy using the Vanderbilt regimen in patients with a poor prognosis non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: We retrospectively analyzed the results of two pilot studies, which enrolled the patients aged 60 years or less, with a previously untreated NHL of intermediate grade on the Working formulation, having 2 or 3 adverse prognostic factors on the age- adjusted International Prognostic Index. Patients received an intensified induction, with the regimen described by the Vanderbilt group. RESULTS: Thirty-five patients were analyzed. After induction, 29 patients (83%) achieved more than partial response (PR): 22 (63%) complete response (CR) and 7 (20%) PR. Three of the PRs were subsequently converted to CR following consolidation therapy. The overall CR rate, following the completion of treatment, was 71%. The 3-year overall survival (OS) rate of all patients was 53%. In the univariate analysis, age (50 years) was the only factor affecting the OS. The 3-year disease-free survival (DFS) rate of patients with CR was 68%. In the univariate analysis, age and bone marrow involvement were the factors affecting the DFS. Two patients died from the treatment-related toxicity of the induction therapy: one due to sepsis and the other due to congestive heart failure. CONCLUSION: Although the CR rate was relatively high, the OS or DFS of patients with a poor prognosis NHL, who had received the intensified induction using the Vanderbilt regimen, were no different from those that had received the conventional chemotherapy, as reported by the International Prognostic Index Project. However, the OS or DFS in the young patient groups were encouraging. To test the hypothesized benefits of our approach in the young patient groups, a larger cohort of patients aged 50 years or less should be studied. PMID- 26680885 TI - actate Dehydrogenase (LDH) as a Tumor Marker for Non-small Cell Lung Cancer. AB - PURPOSE: To determine the prognostic value of pre- treatment serum LDH levels and the LDH isoenzyme pattern for non-small cell lung cancer, and to determine the relationship between the response to chemotherapy and the changes in serum LDH levels following chemotherapy. MATERIALS AND METHODS: Patients with pathologically confirmed non-small cell lung cancer were entered onto this study. Their serum LDH levels were assessed prior to chemotherapy, with the LDH isoenzyme being assessed in patients with high initial serum LDH levels. The serum LDH levels were re-assessed following 2 cycles of chemotherapy. The relationship between the response to chemotherapy, pre-treatment serum LDH levels and LDH isoenzyme pattern and the changes in serum LDH levels, following chemotherapy, were evaluated. RESULTS: 49 patients were entered onto this study. The pre-treatment serum LDH levels were normal in 26 patients, and elevated in 23. The LDH isoenzyme was evaluated in 15 patients, with LDH2 being elevated the most frequently. The response rate to chemotherapy was 42.9% in all 42 patients able to be evaluated, 45.8% in patients with normal serum LDH levels and 41.2% in patients with elevated serum LDH levels. This difference was not statistically significant (p=0.767). The median survival was 37 weeks in all patients able to be evaluated, 38 weeks in those with normal serum LDH levels and 31 weeks in those with elevated serum LDH levels. These differences were not statistically significant (p=0.202). The patients with normal serum LDH levels following chemotherapy were more responsive to chemotherapy than those with elevated serum LDH levels following chemotherapy (response rate 51.4% vs. 0%, p=0.027). CONCLUSION: The LDH2 are most commonly elevated in non small cell lung cancer patients. The pre-treatment serum LDH levels do not reflect the prognosis accurately. The serum LDH levels following chemotherapy are associated with the response to chemotherapy. PMID- 26680884 TI - Phase II Study of Topotecan and Etoposide as Second-line Treatment in Chemotherapy-refractory Small-cell Lung Cancer. AB - PURPOSE: Refractory small-cell lung cancer (SCLC) has a poor prognosis, and current salvage chemotherapy for refractory SCLC, such as CAV (cyclophosphamide, adriamycin, vincristine) or topotecan, has an unsatisfactory outcome, with a response rate and overall survival of less than 10% and 6 months, respectively. This phase II study evaluated the role of topotecan combined with etoposide in SCLC patients that have progressed, or relapsed, within 3 months following completion of the initial chemotherapy. MATERIALS AND METHODS: Twenty-seven patients were entered into this study. Eligible patients had an ECOG performance status of less than, or equal to, 2, at least one bidimensionally measurable lesion and adequate end organ function. IV topotecan, 1.0 mg/m2/d for 5 consecutive days, and etoposide, 100 mg/m2/d through days 1 to 3, were administered every 3 weeks until disease progression or undue toxicity. RESULTS: The major toxicity was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocy-topenia occurred in 14.2, 34.8, and 27.3% of cycles, respectively. There was no treatment-related death, and other non-hematologic toxicities were generally mild. Four patients achieved partial responses, with a response rate RR of 14.8%. The progression-free survival PFS ranged from 1 to 7 months, with a median of 2.0 months (95% confidence interval 1.22~2.78 months). Twenty-five patients died, with a median overall survival of 5.5 months (ranging from 1 to 21 months, 95% CI 4.32~6.68 months), and the 6-month survival rate was 32.1% (95% confidence interval 14.4~49.8%). CONCLUSION: The combination of topotecan and etoposide chemotherapy showed a modest response rate, but failed to prolong survival of refractory SCLC patients compared to topotecan monotherapy. PMID- 26680886 TI - Preliminary Results of Paclitaxel, Cisplatin and Concurrent High-Dose Radiation Therapy for Locally Advanced Non-Small-Cell Lung Cancer. AB - PURPOSE: To investigate the feasibility, toxicity and response rate, of concurrent chemoradiation therapy with paclitaxel/cisplatin in stage III locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between May 1999 and December 2000, 80 patients with stage III NSCLC were enrolled in a prospective protocol. Radiotherapy was given to a total dose of 70.2 Gy (daily fraction of 1.8 Gy for 5 days), over an 8 week period, on the gross tumor volume, combined with chemotherapy. The concurrent chemotherapy consisted of paclitaxel (40 mg/m2) and 20 mg/m2 cisplatin per week for 8 consecutive weeks. All patients received 3-D conformal radiotherapy using CT-simulated planning. Acute toxicities were evaluated by the RTOG scale. The median follow-up period was 16 months, ranging from 3 to 29 months. RESULTS: Of the 80 patients, 71 received treatment per protocol, with minor variation of protocol delivery. The median age of the patients was 60 years. Karnofsky Performance status were 100 and 90 in 62 patients, and 80 and 70 in 9, respectively. Weight loss of less than 5% for 6 months was observed in 22 patients. The response to treatment was evaluated from the radiological findings. Complete and partial responses were observed in 8 and 51 patients, respectively. Ultimately, 82% of patients (included complete responses: 8 cases) obtained more than a partial response. Although, radiation induced esophagitis was the most common treatment related toxicity, occurring in 44 patients (69%), severe radiation esophagitis like, grade 3, was observed in only 3 patients, and the most acute toxicities had completely recovered 1 month following treatment. The overall 2-year actuarial and progression free survivals were 56 and 45%, respectively. CONCLUSION: This combined modality has activity with manageable toxicity and 23 months in mean survival time in patients with stage III NSCLC. A longer follow up will be required to realise the expected higher survival of these results. PMID- 26680887 TI - Effect of Vinorelbine, Ifosfamide and Cisplatin Combination Chemotherapy in Stage III-IV Non-Small-Cell Lung Cancer. AB - PURPOSE: To evaluate the response rates, toxicitiesy, and survival rates, to vinorelbine (Navelbine(R)), cisplatin and ifosfamide combination chemotherapy, of the patients with inoperable NSCLC (stage III and IV), who received vinorelbine (Navelbine(R)), cisplatin, ifosfamide combinationthe mentioned chemotherapy every 4 weeks. MATERIALS AND METHODS: This study included 26 patients with inoperable NSCLC (stage III and IV), who attended St. Vincent's Hospital Bbetween April 1999 and December 2001, 26 patients were included at St.Vincent's Hospital. The chemotherapy regimen consisted of vinorelbine (25 mg/m2 on days 1 and 8), ifosfamide (1,500 mg/m2 on days 1- and 2 with mesna), and cisplatin (30 mg/m2 on days 1- to 3). The cycles were administered every 4 weeks. A 25% reduction in the doses reduction was applied into subsequent courses if there werewas grade 3~4 neutropenia. RESULTS: The median age was 63 (range, 44~73) years and the male : to female ratio was 19 : 7. One patient had stage IIIa, 6 had stage IIIb and 19 had stage IV. Twenty two patients had an ECOG performance status of 0 or 1, andwith 4 hadhave one of 2. Eighteen of the patients had adenocarcinoma, 7 had squamous cell carcinomas, and 1 had an undifferentiated NSCLC. Two patients were innot able to be evaluatedble due to follow-up loss. Among Of the 24 patients able to be evaluatedble patients, 1 patient had a complete response and 9 patients hada partial responses, and thewith an overall response rate wasof 41.7%. During a total of 104 cycles, grade 3 neutropenia occurred in 29%, grade 4 neutropenia in 12%, grade 3~4 thrombocytopenia in 4%, grade 3 anemia in 11%, and grade 3~4 mucositis in 2%. The mean time to progression was 6.4 months (range 1~13) and the median overall survival was 10 months (range 1.5~32). CONCLUSION: The combination of vinorelbine, ifosfamide and cisplatin, in the dose and schedule employed in this study, shows an response rate of 41.7%, but, because grade 3- or 4 neutropenia occurred in 41%, a careful investigation is needed. PMID- 26680888 TI - Polymorphisms of p53, p21 and IRF-1 and Cervical Cancer Susceptibility in Korean Women. AB - PURPOSE: The aim of this study was to identify gene- gene and gene-environmental factor on cervical carcinogenesis in Korean women. MATERIALS AND METHODS: We evaluated 185 women patients who had cervical cancer with 345 normal control healthy women. The single nucleotide polymorphisms (SNPs) of the p53 codon 72, the p21 codon 31 and the IRF-1 intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The difference of each SNP, gene-gene and gene-environmental interaction between normal controls and patients, were evaluated in an adjusted environmental background. RESULTS: With regard to environmental factors, the cervical cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and with the increased number of children borne. The women who had p53 (Arg/Arg), IRF-1 (T/T) and an education of less than 6 years showed a 14.7 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and an education of more than 15 years. The women who had p53 (Arg/Arg), p21 (Ser/Ser) and more than 3 children showed a 6.4 fold increased risk of cervical cancer than those women who had p53 (~Pro), p21 (~Arg) and had borne no child. The women who had p53 (Arg/Arg), IRF-1 (T/T) and had experience of first sexual intercourse before the age of 22-years showed a 5.5 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and had experience of first sexual intercourse after the age of 26-years. CONCLUSION: We found that the level of education, the age at first intercourse, and the number of children borne, were independent risk factors in cervical carcinogenesis. The specific combination of p53, p21 and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervical carcinogenesis of Korean women. PMID- 26680889 TI - Results of Curative Radiotherapy Alone in Patients with Uterine Cervical Carcinomas. AB - PURPOSE: To evaluate the role of curative radiotherapy alone in the treatment of uterine cervical carcinomas, by a retrospective analysis with respects to survival and pelvic control, and to find any risk factors of failure. MATERIALS AND METHODS: Between Jan. 1990 and Dec. 1995, a total of 187 patients, diagnosed with uterine cervical carcinomas in FIGO stages greater than IA, were treated by curative radiotherapy alone with no chemotherapy. The ages of the patients ranged from 26 to 80 years, with a median of 60 years. The number of patients diagnosed with squamous cell carcinomas were 183 (97.9%). The number of patients with FIGO stage IB1, IB2, IIA, IIB, IIIA, IIIB and IVA were 61 (32.6%), 7 (3.7%), 43 (23.0%), 62 (33.3%), 3 (1.6%), 7 (3.7%) and 4 (2.1%), respectively. External radiotherapy was performed with 6 MV or 10 MV X-rays, with a dose range of 19.8 Gy~ 50.4 Gy (median; 30.6), to whole pelvis. Intracavitary radiation (ICR) was then performed using a high-dose rate remote controlled afterloader with radioisotopes of Co-60 and Cs-137. The fraction size of the ICR was 5 Gy twice a week, and was delivered up to total doses of 10 Gy~ 55 Gy (median; 40). After the ICR, additional pelvic external radiotherapy with midline shielding width of 4 cm was performed with the dose range of 0~30.6 Gy (median; 19.8), and the resultant total doses of A points ranged between 49.8 Gy and 86.0 Gy (median; 70.6). RESULTS: The five-year overall survival rates of FIGO IB1, IB2, IIA, IIB, III and IVA were 88.3%, 83.3%, 86.1%, 65.2%, 60.0% and 50.0%, respectively (p=0.005). The pelvic control rates of each stage were 90.1%, 85.7%, 86.1%, 69.4%, 68.6% and 50.0%, respectively (p=0.03). From the multivariate analysis, the radiation response and tumor diameter were found to be significant factors affecting the overall survival. The significant factors influencing pelvic control were the radiation response and pre-treatment hemoglobin level. CONCLUSION: The radiation response and tumor diameter were significant factors affecting survival, so patients with tumor diameters greater than 4 cm should be considered for a combined modality, such as concurrent chemoradiotherapy. PMID- 26680890 TI - Antitumor Activity of Oxaliplatin, 5-FU and Paclitaxel Given Alone or in Combination with ZD1839 in Human Gastric Carcinoma Cells in vitro. AB - PURPOSE: Oxaliplatin (LOHP), 5-FU, and paclitaxel (PTX) are considered highly active against advanced gastric carcinomas, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, ZD1839 is considered as a good candidate for the treatment of gastric cancers when given alone or in combination with cytotoxic agents. The present study evaluated the antitumor effects of these agents in SNU-1 human gastric cancer cells either alone or when given as a doublet (i.e., as a cytotoxic-cytostatic combination). MATERIALS AND METHODS: We selected SNU-1 cells that showed DNA mismatch repair (MMR) deficiency and EGFR overexpression. Growth inhibition was measured by MTT and by direct cell counting and cell cycle distribution by flow cytometry. The combination index (CI) was used to describe synergistic interaction. RESULTS: The four drugs showed IC50s ranging from 1.81 nM to 13.2microM. MTT assay appeared to underestimate the cytotoxicity of PTX, which was attributed to a significant resistant fraction (32%). LOHP and PTX induced G2/M arrest, 5-FU increased in S phase, and ZD1839 in creased in G1 in a concentration dependent manner. PTX ZD1839 showed the greatest synergism and LOHP ZD1839 showed a similar result. The cell cycle effect of PTX was potentiated by the coadministration of ZD1839. A previously developed cytostatic TPi model was used to assess the contribution of cell cycle arrest to overall growth inhibition, and 64% and 80% of the overall growth inhibition was attributed to cell cycle arrest for LOHP and PTX, when exposed to 7.55microM and 10 nM for 72 hr, respectively. CONCLUSION: This study demonstrates the antitumor activity and significant cell cycle arrest effect of ZD1839 against human gastric carcinoma cells and its synergistic interaction with LOHP and PTX. These results provide a preclinical rationale for the clinical development of ZD1839 and its use in combination with LOHP or PTX against human gastric cancers that express EGFR. PMID- 26680891 TI - Salvage Treatment for Advanced Gastric Cancer Using FEP (5-FU, Etoposide, Cisplatin) Combination Chemotherapy. AB - PURPOSE: There is no effective treatment for patients with advanced gastric cancer having failed to respond to first line chemotherapy. The aim of this study was to evaluate the therapeutic activity, and safety, of a FEP regimen in patients with a recurrence of, or metastatic, gastric cancer that had been unresponsive to primary chemotherapy. MATERIALS AND METHODS: Recurred or metastatic gastric cancer patients that did not respond to a 5-fluorouracil based regimen were entered into this trial. The patients were treated with FEP (5-FU, etoposide and cisplatin) as salvage chemotherapy. The treatment regimen was 5-FU (900 mg/m2/day) by continuous infusion for 3 days, etoposide (90 mg/m2/day) on days 1, 2 and 3, and cisplatin (60 mg/m2/day) on day 2. This treatment was repeated every 3 weeks. RESULTS: Between December 1997 and October 2001, 28 patients were enrolled to the study. The response rate was 32.1% (95% CI 15.5~57.8%). The median times to progression and survival duration were 23~33 weeks, respectively. Among a total of 187 cycles of chemotherapy, the grade 3 and 4 hematological toxicities were leukopenia (6.4%), thrombocytopenia (1.6%), and grade 3 non-hematological side effects of nausea/vomiting (17.9%). CONCLUSION: FEP combination chemotherapy seems to be an effective treatment regimen for gastric cancer as salvage chemotherapy. To confirm these results, large scale of clinical trials will be required. PMID- 26680892 TI - Interrelation of Cyclin D1, Cyclin E, and p27Kip1 Expression on Tissue Arrays of Breast Cancer. AB - PURPOSE: To evaluate the clinical impact of the altered expression of cell cycle regulators in stage I and II breast cancers. MATERIALS AND METHODS: The interaction between cyclin D1/E and p27Kip1 expressions were analyzed using tissue microarray (TMA) technology in 133 breast cancers. Data from the immunohistochemical assays of 3 molecules were merged, and analyzed, with a Ki67 labeling index of the same tumors. RESULTS: Cyclin D1 was expressed in 72 breast carcinomas (54.1%) and cyclin E in 60 (45.1%) out of the 133 breast carcinomas. Expressions of cyclin D1 and cyclin E were inversely related to each other, and significantly associated with the estrogen receptor (ER) expression and differentiation of the breast carcinoma. The expression of cyclin E was significantly decreased in tumors expressing cyclin D1 (p=0.022). There was a trend for cyclin D1 expression to increase in tumors expressing p27Kip1 (p=0.053), but the expression of cyclin E did not correlate with p27Kip1 expression. The Ki67 labeling index was markedly increased in tumors expressing cyclin E, whereas it was significantly decreased in the cyclin D1 or p27Kip1 expressing-tumors. From survival analysis, cyclin E expression was the only significant variable for the prediction of poor survival. CONCLUSION: The abnormal expressions of cell cycle regulatory molecules are prevalent, and interrelated with each other in breast cancer. Integration of TMA technology allowed a high-throughput analysis for correlating molecular the in situ findings, with the clinico-pathologic information. Among the three molecules studied, the cyclin E had a prognostic implication for stage I and II breast cancer. PMID- 26680893 TI - Metastasis to the Thigh Skeletal Muscle from an Adenocarcinoma of the Duodenum. AB - Skeletal muscle is one of the most unusual metastatic sites for any malignancy. Duodenal cancer is extremely rare, and no cases of skeletal muscle metastasis from duodenal cancer have been reported. We report here in a case of metastasis to the skeletal muscle of the left thigh from duodenal cancer. Our patient was a 47-year-old man, exhibiting a painful mass in the posterior aspect of his left thigh over a 4 month period. An imaging study, and a biopsy, revealed a duodenal adenocarcinoma metastasize to the skeletal muscle. The patient refused chemotherapy and has followed up for 4 months. PMID- 26680894 TI - Therapeutics Approaches in the Treatment of Limited Small-Cell Lung Cancer. PMID- 26680895 TI - Cancer Incidence in Korea. AB - PURPOSE: We estimated the incidence of cancer in Korea. MATERIALS AND METHODS: The indicence of cancer was estimated using national mortality data, and the incidence data from four frontier regional cancer registries, including Kangwha, Seoul, Busan and Deagu. These four registries served a population about seventeen million, which is almost 38% of entire population in Korea. RESULTS: The overall age-standardized incidence rates (ASR) were 287.0 and 163.1 per 100,000 for males and females, respectively. Among males, stomach cancer was the most frequent (ASR 69.6), followed by lung cancers, including bronchus cancer (ASR 54.5), liver cancer (ASR 47.0) and colo-rectal cancer (ASR 25.2). The most frequent sites of cancer in females, by rank order, were stomach (ASR 26.8), breast (ASR 20.1), uterine cervix (ASR 18.0), colo-rectum (ASR 15.9), lung (ASR 13.0) and liver (ASR 12.0). CONCLUSION: It is hoped that these results will provide valuable leads for cancer research and cancer control in Korea. PMID- 26680896 TI - Concurrent Etoposide/Cisplatin Combination Chemotherapy (EP) and Thoracic Radiotherapy after Two Cycles of EP for Limited Stage Small Cell Lung Cancer. AB - PURPOSE: s: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP). MATERIALS AND METHODS: EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation. RESULTS: Fifty patients were enrolled. Thirty five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation. CONCLUSION: The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy. PMID- 26680897 TI - A Phase II Study of Ifosfamide, Carboplatin, and Epirubicin (ICE) Combination Chemotherapy for Extensive Disease of Small Cell Lung Cancer. AB - PURPOSE: To evaluate the efficacy and safety of ifosfamide, carboplatin and epirubicin (ICE) combination chemotherapy for extensive disease small cell lung cancer (SCLC) patients, who had received no previous chemotherapy, we performed phase II trial between August 1998 and January 2001. MATERIALS AND METHODS: The study group comprised of 21 patients. Ifosfamide, 1,500 mg/m2, was given with mesna, 900 mg/m2, intravenously for 12 hours on days 1, 2 and 3, and carboplatin, 4.5 mg/ml/min, for target AUC, and epirubicin, 60 mg/m2, were given intravenously for 90 minutes on day 1. The cycle of treatment was repeated at 4 week intervals. RESULTS: Twenty-one patients with extensive disease SCLC were treated at Hallym University between August 1998 and January 2001. One patient was unable to be evaluated because of lost to follow-up. Of the 20 patients able to be evaluated, an objective response was observed in 13 (65%). There were no complete responses. The median response duration, time to progression and median overall survival were 15.4, 18.3 and 34 weeks, respectively. Toxicities were acceptable, with dose reduction for myelosuppression necessary in only a minority of the patients. A total of 85 cycles of chemotherapy were given to the patients. The median number of cycles completed was 4. Grade III and IV hematological toxicities included anemia (4.7%), neutropenia (3.5%) and thrombocytopenia (3.5%). Most non hematological toxicities were grade I or II. CONCLUSION: These results suggested that ICE combination chemotherapy for extensive disease SCLC is effective, and can be safely administered with acceptable toxicities. PMID- 26680898 TI - Oral Etoposide, Ifosfamide and Cisplatin in the Treatment of Extensive Disease Small Cell Lung Cancer. AB - PURPOSE: The combination of cisplatin and etoposide has been a common first line regimen for the treatment of small cell lung cancer (SCLC). The schedule dependence, and equal efficacy, of the oral and intravenous dosing of etoposide has led to prolonged administration of oral etoposide, which is known to produce an encouraging response in SCLC. To improve the efficacy of the cisplatin/etoposide combination, we administered oral etoposide, with added ifosfamide, which had significant single agent activity against SCLC. We conducted this study to evaluate the efficacy and toxicity of the cisplatin, ifosfamide and oral etoposide (PIE) combination in patients with extensive small cell lung cancer. MATERIALS AND METHODS: Twenty-five patients with histologically confirmed extensive small cell lung cancer were enrolled into this study between January 2000 and May 2002. They were treated with, cisplatin at 20 mg/ m2/day, ifosfamide 1.5 g/m2/day, with mesna (all given intravenously on Days 1~3), and oral etoposide 50 mg/m2 on days 4~17. This cycle was repeated every 4 weeks for up to 6 cycles. We evaluated the corresponding disease responses and toxicities. RESULTS: The patients' characteristics were as follows: median age 65 years (32~75), 19 males and 6 females. The performance stati were ECOG 0 in 3 patients, ECOG 1 in 12 and ECOG 2 in 10. Sixteen patients had a partial response, 2 had a stable disease and 4 had a progressive disease. Thus, the overall objective response rate was 72.7% (95% CI: 49.6~88.4%), with a median response duration of 7 months (95% CI: 3.5~10.5 months). Myelosuppression was the major observed toxicity. Grades III and IV neutropenia were observed in 42 (46.1%) of the 91 cycles. Significant non-hematological toxicities (>or=Grade III) were uncommon, with the exception of nausea and vomiting. CONCLUSION: The response rate to the combination of cisplatin, ifosfamide and oral etoposide was similar to that of other combination chemotherapy studies in patients with extensive disease small cell lung cancer. The toxicity of the regimen was considered acceptable. PMID- 26680899 TI - SB203580, a P38 MAPK Inhibitor, Blocks in vitro Invasion by Human Gastric SNU-638 Cells. AB - PURPOSE: The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process. MATERIALS AND METHODS: Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively. RESULTS: Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580. CONCLUSION: Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis. PMID- 26680900 TI - No Association between Catalase Gene Polymorphism and Gastric Carcinoma and Hepatocellular Carcinoma in Koreans. AB - PURPOSE: Oxidative stress has been implicated in the pathogenesis of various diseases. Catalase is one of the main defense mechanisms against oxidative stress. To examine the possible relationship between oxidative stress, and gastric and hepatocellular carcinomas, HinfI restriction length polymorphism (RFLP) in the human catalase gene was assessed. MATERIALS AND METHODS: The genotype and allele frequencies in the promoter region of the catalase gene were studied by PCR-RFLP in 108 Korean controls, 80 Korean gastric carcinoma (GC) and 106 Korean hepatocellular carcinoma (HCC) patients. RESULTS: No statistically significant differences were found in the genotypic distribution and allelic frequencies between the controls and both types of carcinoma patient. CONCLUSION: To address the possible contribution of oxidative stresses to the pathogenesis of gastric and hepatocellular carcinomas, the associations between the catalase gene polymorphism and GC and HCC susceptibilities were studied. As a result, the catalase gene polymorphism was found not to be determinant of GC and HCC susceptibilities. Further studies are required on various other oxidative stress related genes to elucidate the mechanisms of GC and HCC. PMID- 26680901 TI - l-myc Polymorphism in Gastric Cancer, Lung Cancer, and Hepatocellular Carcinoma. AB - PURPOSE: This study was performed to see if a particular polymorphism in the l myc, a nuclear oncogene at the 1p32 locus, might be associated with greater risk of gastric cancer, lung cancer and hepatocellular carcinomas (HCC) in Korean patients. MATERIALS AND METHODS: Genomic DNA, derived from patients diagnosed with gastric cancer (n=57), lung cancer (n=39), HCC (n=35) and healthy individuals (n= 176), was examined. The l-myc polymorphism under study was visualized by PCR followed by EcoRI digestion. RESULTS: There was no significant difference in the distribution of the l-myc polymorphism genotypes and allele frequencies between the cancer patients and the controls. CONCLUSION: The l-myc polymorphism does not appear to be indicative of elevated risk of cancers of the stomach, lung and HCC. PMID- 26680902 TI - High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Persistent/Relapsed Ovarian Cancer. AB - PURPOSE: High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report. MATERIALS AND METHODS: We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals. RESULTS: Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths. CONCLUSION: HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders. PMID- 26680903 TI - Antisense Deoxyoligonucleotides Inhibit Activities of Matrix Metalloproteinase-2 in Human Fibrosarcoma HT1080 Cells. AB - PURPOSE: MMP-2, 72 kDa-type IV collagenase, plays a major role in the migration and growth of tumor cells, a process that requires the disintegration of basement membrane. Activation of MMP-2 is correlated with the invasiveness of various tumors. The aim of this study was to determine the sequence-specific phosphorothioated oligodeoxynucleotides (ODNs) inhibiting the translation of MMP 2 mRNA and the subsequent invasiveness of tumor cells. MATERIALS AND METHODS: Eight types of antisense ODNs were designed and each (8micro gram/ml) were transfected into HT1080 cells. The effects of these antisense ODNs on MMP expression were examined by gelatin zymography, Western blot, Northern blot and matrigel assay. RESULTS: Antisense-5 (+904~923), antisense-6 (+1274~+1293) and antisense-7 (+1646~+1665) reduced the MMP-2 activity of the culture supernatant in HT1080 fibrosarcoma cells. Treatment with antisense-6 showed inhibition of MMP 2 mRNA and protein, and in vitro invasion in a dose-dependent manner. CONCLUSION: Antisense-6 might be one of the therapeutic candidates for tumor invasion and metastasis. PMID- 26680904 TI - Ependymoma: a Retrospective Analysis of 25 Cases. AB - PURPOSE: We evaluated the patterns of failure, survival rate, prognostic factors and treatment related complication in postoperative radiation treatment of patients with ependymoma. MATERIALS AND METHODS: We retrospectively analyzed 25 patients with histologically confirmed ependymoma treated between Jun. 1990 and Jun. 2001 with postoperative radiotherapy at Asan Medical Center. The study group comprised of 16 men and 9 women, with a median age of 23 years; including 6 supratentorial, 15 infratentorial and 4 spinal cord lesions. The extents of resection were ranked as either: gross total, near total, subtotal, partial resection or biopsy, with these types of surgical resection being performed in 13, 3, 6, 1 and 2 patients, respectively. Twelve of the patients had low grade ependymoma, and the other 13 a high grade tumor. The postoperative irradiation was administered using 4 MV or 6 MV photons, up to median dose of 55.0 Gy (range, 45.0~59.4 Gy), with the radiation field encompassing the preoperative tumor volume plus a 2 cm margin. Only 8 of the patients received either pre- or postoperative chemotherapy. The median follow-up period of survivors was 43 months. RESULTS: Ten of the 25 patients (40%) developed a recurrence, and 5 died. Of the 10 recurred patients, 6 showed an in-field recurrence, and one developed both an in-field and an out of field recurrence. The remaining 3 patients showed an out of field recurrence, including one case with a leptomeningeal recurrence. The 5-year overall survival, and progression-free, survival rates were 74.0 and 56.1%, respectively. The histological grades were statistically significant prognostic factors of the overall and progression-free survival rates. There were no significant treatment related complications, with the exception of one case of panhypopituitarism, which occurred 30 months after completion of the radiotherapy. CONCLUSION: The main pattern of recurrence was due to local failure. In order to improve the local control, and to reduce complications, advanced radiation treatment techniques, such as 3 dimensional radiotherapy, may be needed. PMID- 26680905 TI - A Case of Primary Gastric Choriocarcinoma Presenting with Amenorrhea. AB - Primary gastric choriocarcinomas are very rare, and their prognosis is extremely poor. A 37-year-old woman presented with amenorrhea, vaginal spotting and severe nausea, which mimicked a pregnancy and gestational trophoblastic disease. The serum level of the beta-subunit of human chorionic gonadotrophin (beta-hCG) was significantly increased. An endoscopic biopsy of the stomach mass showed the features of a choriocarcinoma, with marked anaplasia and necrosis. Immunohistochemical staining for beta-hCG showed positive results in the choriocarcinoma. Chemotherapy for the choriocarcinoma was administered, but she died 8 months following diagnosis. PMID- 26680906 TI - A Case of Extraskeletal Ewing's Sarcoma Arising from Duodenum. AB - Extraskeletal Ewing's sarcomas (EES) are rare. Recently, Ewing's sarcoma of the bone, primitive neuroectodermal tumor (PNET), Askin tumor and EES have been included into the family of Ewing's tumors, due to the overlapping features relating to their clinico-pathological and cytogenetic appearance. We experienced a case of an EES arising from the duodenum in a 14-year-old girl who presented with hematemesis and epigastric discomfort. A duodenal biopsy specimen revealed the infiltration of small round cells and rich vasculatures, with immunohistochemical finding of MIC-2 (CD99) (+), vimentin (+), CD56 (NCAM) (+), LCA (-), T-cell (-), B-cell (-), CD43 (-) and CD68 (-). She was treated with several cycles of multiagent chemotherapy, and achieved an initial partial response, but rapid progression of tumor followed, so she was treated with surgical excision. This is the first case report of an EES arising from the duodenum in the literature. PMID- 26680907 TI - Molecular Markers in Gastric Cancer: Can They Predict Prognosis? PMID- 26680908 TI - The Serum Assay of Soluble CD44 Standard, CD44 Variant 5, and CD44 Variant 6 in Patients with Gastric Cancer. AB - PURPOSE: Alternative splicing of CD44 and aberrant levels of soluble CD44 (sCD44) protein in the serum of cancer patients has been correlated to tumor progression and metastasis. The purpose of this study was to evaluate the concentrations, and the prognostic potential of sCD44s, sCD44v5 and sCD44v6, in patients with gastric cancer. MATERIALS AND METHODS: The serum levels of sCD44s, sCD44v5 and sCD44v6 were determined quantitatively using an enzyme-linked immunosorbent assay. Serum samples were obtained from 116 patients with gastric cancer, both before and after surgery, and from 30 healthy controls. RESULTS: The serum sCD44v6 levels were significantly higher in patients with gastric cancer than in the healthy controls, whereas those of sCD44s and sCD44v5 were no different. The surgical resection of the tumor resulted in a significant reduction in all the sCD44 proteins, whereas if a surgical resection was not performed the concentrations of the sCD44v5 and sCD44v6 were not reduced prior to surgery. The serum sCD44v6 levels correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. CONCLUSION: The preoperative serum level of sCD44v6 in patients with gastric cancer was significantly higher than that in the healthy controls, and correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. These results suggest that an elevation of the serum sCD44v6 level might be used as a new predictor of tumor invasiveness, and poor prognosis, in patients with gastric cancer. PMID- 26680909 TI - Overexpression of c-met Protein in Gastric Cancer and Role of uPAR as a Therapeutic Target. AB - PURPOSE: One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis. MATERIALS AND METHODS: The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay. RESULTS: Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p<0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (> or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p<0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p<0.05). CONCLUSION: The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer. PMID- 26680910 TI - RImmunohistochemical Evaluation of E-cadherin/catenin (alpha-, beta-, gamma catenin and p120CTN) Complex Expression in Early Gastric Cancer. AB - PURPOSE: The significance of abnormal E-cadherin/ catenin complex expression and the correlation of each of its components in cancer remain unclear. This study aimed to characterize the clinical significance of the abnormal membrane expression of the E-cadherin/ catenin complex and the localization patterns of the beta- catenin and p120CTN in early gastric cancer. MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, alpha-, beta- and gamma-catenin and p120CTN were performed on 47 early gastric cancer specimens. The patterns of membrange expression of the E-cadherin/catenin complex, and the localization patterns of the beta-catenin and p120CTN, were semi quantitatively graded as loss, reduced, preserved or negative and positive. RESULTS: An abnormal immunoreactivity of at least one of E-cadherin/catenin complex proteins was noted in 46 (97.8%) of the 47 early gastric cancer cases. There were no significant correlations of the membrane E-cadherin/catenin expression with, either, sex, age, location, size, macroscopic type, depth of invasion or lymphovascular invasion. Abnormal expressions of membrane E-cadherin, beta-catenin and gamma catenin were more frequent in the diffuse-type than in the intestinal type. No linear correlation was shown for the beta-catenin between the membrane and cytoplasmic expressions. Nuclear staining of the beta-catenin was observed in 5 (10.6%) cases, but nuclear staining of the p120CTN, a promotor of Kaiso transcriptional factor, was not seen. CONCLUSION: These results suggest that alterations of the E-cadherin/catenin complex may be involved in the early stages of gastric cancer. Although beta-catenin functions as a transcriptional factor, the inactivation of membrane E-cadherin does not appear to result in significant increases in the level of cytoplasmic beta-catenin. Kaiso transcriptional factor may not be involved in the early carcinogenesis of gastric cancer. PMID- 26680911 TI - Phase I and Pharmacokinetic Study of Intraoperative Intraperitoneal Heptaplatin in Patients with Surgically Resected Advanced Gastric Cancer. AB - PURPOSE: Heptaplatin, a new platinum analog, has favorable toxicity profiles and antitumor activity, comparable to those of cisplatin, in the treatment of gastric cancer. This study was designed to define the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and pharmacokinetics of heptaplatin administered by an intraperitoneal route in patients with resected advanced gastric cancer. MATERIALS AND METHODS: Seventeen patients with resected advanced gastric cancer were entered onto the study. After completion of a curative resection and an astomosis, heptaplatin was administered intraperiton eally in one liter of 5% dextrose solution. The starting heptaplatin dose was 400 mg/m2 of the body surface area, and was escalated in 200 mg/m2 increments, to cohorts of three patients. A pharmacokinetic analysis was carried out to determine the total and ultrafiltratable platinum concentrations in the plasma, peritoneal fluid, and urine. RESULTS: Patients were unable to tolerate a 1, 000 mg/m2 dose level, and at 800 mg/m2, reVersible Grade III toxic ities, including elevated creatinine, proteinuria, hypon- atremia, abdominal pain, and intraabdominal bleeding were noted. No significant toxicity was noted up to a 600 mg/m2 dose level. The ratio of the peak peritoneal to peak plasma drug concentrations were 19.4, 16.6 and 22.8 at doses of 400 mg/m2, 600 mg/m2 and 800 mg/m2, respectively. The pharmacological advantage, expressed as the peritoneal to plasma AUC ratio ranged from 4.3 to 7.0. CONCLUSION: Heptaplatin can be delivered by an intra peritoneal route, with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The MTD of intraperitoneal heptaplatin was 800 mg/m2. The major DLTs were nephrotoxicity and intraabdominal bleeding. The recommended starting dose for a subsequent study would be 600 mg/m2. PMID- 26680912 TI - A Multi-Center, Phase II Clinical Trial of Genexol(R) (Paclitaxel) and Cisplatin for Patients with Non-Small Cell Lung Cancer. AB - PURPOSE: A combination of paclitaxel and cisplatin is an effective and safe regimen for advanced non-small cell lung cancer (NSCLC). We conducted a multi center, phase II trial to evaluate the efficacy and safety of Genexol(R) (paclitaxel) and cisplatin in patients with NSCLC. MATERIALS AND METHODS: Chemotherapy-na ve patients having histologically confirmed NSCLC were enrolled. Genexol(R) was administered at 175 mg/m2 as a 3-hour intravenous infusion and cisplatin at 75 mg/m2 as an intravenous infusion on day 1 every 3 weeks. RESULTS: Twenty-five of 27 patients that were entered from 5 hospitals between Jan 2001 and Aug 2001 received chemotherapy. On an intent-to-treat basis, 9 patients (36%) achieved a partial response, 7 patients (28%) a stable disease, and 5 patients (20%) The overall response rate was 36% (95% CI, 17 to 55%). progressed. The median duration of the response was 7.8 months (95% CI, 6.6 to 9.0 months). The median time to progression was 7.4 months (95% CI, 5.3 to 9.5 months), and median overall survival was 13.3 months (95% CI, 10.8 to 15.9 months) for the intent-to treat population. The major oxicity was hematological, with grade 3 and 4 neutropenia in 10% (10/106) of the total cycles. The non-hematologic oxicity was mild, and grade 3 emesis was observed in 2 patients (8%). One patient experienced a moderate degree hypersensitivity reaction. CONCLUSION: The results suggest that a combination of Genexol(R) and cisplatin is an effective and well-tolerated regimen for patients with NSCLC. PMID- 26680914 TI - The Effect of More Aggressive Surgery in Esophageal Cancer. AB - PURPOSE: One of the most controversial aspects of surgery for esophageal cancer is the appropriate extent of lymphadenectomy to achieve the best outcome. The purpose of this study was to clarify the effects of an extended lymphadenectomy (complete 2-field lymphadenectomy; complete 2-FL or 3-field lymphadenectomy; 3 FL) in esophageal cancer surgery. MATERIALS AND METHODS: In order to prevent a local recurrence and improve the long-term survival following surgery, an extended lymphadenectomy has systematically been performed at four hospitals of the Catholic University College of Medicine since 1995. And since that time, until the end of 2001, a total of 98 patients have undergone the procedure. Their clinical results were compared with those of 54 esophageal cancer patients who received an incomplete 2-field lymphadenectomy (incomplete 2-FL), between 1990 and 1994, at the same hospitals. RESULTS: After an extended lymphadenectomy a recurrence was noted in 41 cases (44.6%), a local recurrence occurred in 23 cases (25.0%) and a metastatic recurrence in 18 (19.6%), with the 5-year survival rate improved to 39.5%, than the 29% of the incomplete 2-FL. There was no difference in the morbidity of the fatal complications and the mortality between the two groups. CONCLUSION: The long survival rate was improved with an extended lymphadenectomy, but the morbidity and mortality rate had not increased. PMID- 26680913 TI - The Estimation of Breast Cancer Disease-Probability by Difference of Individual Susceptibility. AB - PURPOSE: The aims were to evaluate the main risk factors (RFs) of breast cancer and to estimate the individual disease-probability from combinations of RFs in Korean female. MATERIALS AND METHODS: We conducted case-control study of 1, 687 incident cases of invasive carcinoma and 1, 238 controls during 1996~2000. A breast cancer disease-probability model was established by a general modeling process using a multivariate logistic regression model, which included the main Korean RFs and synergistic interaction-terms. RESULTS: The main Korean RFs selected were age, family history of second relatives, BMI, age at first full term pregnancy, breast-feeding, and a special test on the breasts. Two synergisms were observed between age and breast-feeding, and between special test and age at first fullterm pregnancy. The disease-probability and model are shown in Table 4, and Appendix 1. CONCLUSION: The availability of previous Western models was limited for Korean female due to the differences inhazard-rates and the characteristics of breast cancer between Asian and Western females. Due to limited basic data, i.e. incidence, hazard-rate and cancer-cohorts, the developing-probability of breast cancer for Korean females was not calculated. Therefore, the disease-probability was calculated instead. This approach might be more beneficial for Koreans, and help in the decision- making for regular screening or hospital visit-interval, counseling in breast-cancer clinics, prescribing high-risk population, and in educating for primary prevention, although it over-estimates the relative probability compared to the developing probability and the 65% predictive validity. PMID- 26680915 TI - Correlation between Retinoic Acid Sensitivity and IGFBP-3, AFP Protein Expression in Hepatoma Cell Lines. AB - PURPOSE: Retinoic acid (RA) has been known to inhibit the proliferation, and to induce apoptosis, of various cancer cell lines. We investigated the correlation between the protein levels of the RAR and RXR receptor families, IGFBP-3 and AFP, and the RA sensitivity in hepatoma cell lines. MATERIALS AND METHODS: The cell growth inhibition was examined by assaying various 1 to 10muM RA treated hepatoma cell lines. Western blot analysis for the RAR and RXR families, AFP and IGFBP-3 were performed after treatment with 10muM RA. RESULTS: The 1 to 10muM RA treatment induced growth inhibition in the SNU368, SNU354, SNU398 and HepG2 cells. The cell growth of SNU449 and Hep3B were not suppressed by 1muM, but were slightly suppressed by 10muM RA. An increased expression of IGFBP-3 in HepG2, SNU354, SNU398 and SNU368 cells, and a decreased expression of alpha-fetoprotein (AFP), was observed from the western blot analysis in all hepatoma cells tested, whereas no confirmed tendency of RAR expressions was seen. CONCLUSION: Our result showed that the growth inhibition of RA differed according to the sensitivity of the type of cells to RA. We supposed that RA-induced cell growth inhibition may be related to the expressions of IGFBP-3 and AFP, but no exact correlation exists between the growth inhibition and receptor expression status in hepatoma cell lines. PMID- 26680916 TI - The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia. AB - PURPOSE: This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML. PMID- 26680917 TI - Clinical Experience in Conformal Stereotactic Radiotherapy of Irregularly Shaped Intracranial Tumors. AB - PURPOSE: The dosimetric advantages of multiple non-coplanar stationary fields for stereotactic radiotherapy or adiosurgery (SRT/S) are well known. However, this technique is not widely used due to the logistical problems associated with producing and testing customized collimators. We report our experience of SRT/S using multiple non-coplanar stationary fields (conformal SRT/ S). MATERIALS AND METHODS: Between August 1997 and February 2002, we performed frameless SRT/S in 63 patients. We chose conformal SRT/S when the tumor was of a very irregular shape or larger than 4 cm. We obtained three pieces of information: 1) the couch translations required to bring the target point to the isocenter, 2) the distance between the stereotaxic markers in the CT study, and the distance between the markers determined from orthogonal beam films, taken in the anterior- posterior and lateral directions, and 3) the rotational movement of the head position between the CT study and actual treatment position. We evaluated two kinds of data: 1) the precision of the isocenter setup, and 2) the reproducibility of the head position in the a) translational and b) rotational components. RESULTS: Twenty-six of the 63 patients receiving stereotactic treatment received conformal SRT/S. The precision of the isocenter setup for the conformal SRT/S was x=-0.03+/ 0.26 mm, y=0.19+/-0.25 mm and z=-0.20+/-0.27 mm. The reproducibilities of the head position with the conformal SRT/S were 0.5 mm and less than 1degrees C, for the translational and rotational components, in any plane. CONCLUSION: We were able to apply conformal stereotactic irradiation, which has a dosimetric advantage, to irregularly shaped intracranial tumors, with precision and reproducibility of head position for the isocenter setup nearly equivalent to that of frame-based SRS or multiple-arc SRT/S. PMID- 26680918 TI - Site-Specific Mutagenesis in Escherichia coli by Bulky Exocyclic Amino Substituted Guanine and Adenine Derivatives in Double-Stranded or Gapped Plasmids. AB - PURPOSE: 7-Bromomethylbenz[alpha]anthracene is a known mutagen and carcinogen. The mutagenic potency of its two major DNA adducts, i.e., N2 (benz[alpha]anthracen-7-ylmethyl)-2'-deoxyguanosine (b[alpha]a2G) and N6 (benz[alpha]anthracen-7-ylmethyl)-2'-deoxyadenosine (b[alpha]a6A), as well as the simpler benzylated analogs, N2-benzyl-2'-deoxyguanosine (bn2G) and N6-benzyl-2' deoxyadenosine (bn6A), were determined in E. coli. MATERIALS AND METHODS: Double stranded and gapped plasmid vectors were used to determine the mutagenicity of b[alpha]a2G, b[alpha]a6A, bn2G and bn6A in E. coli. The four, suitably protected, bulky exocyclic amino-substituted adducts were incorporated into 16-base oligodeoxyribonucleotides, in place of normal guanine or adenine residues, which form part of the ATG initiation codon for the lacZ' alpha-complementation gene. The site-specifically modified oligodeoxyribonucleotides were then incorporated into double-stranded plasmids, which contained uracil residues in the complementary strand in the vicinity of the initiation codon. The uracil residues lead to the creation of a gap in the complementary strand due to the actions of E. coli uracil-DNA glycosylase and AP endonuclease. Following the transfection of these plasmid vectors into E. coli strain GP102, a lacZ alpha complementing version of the parent strain AB1157, their propensity to induce mutation was investigated. RESULTS: The percentages of mutant colonies produced by the four modified nucleosides, in both the double-stranded and gapped plasmid vectors, were not significantly different from those produced by the unmodified plasmids. The mutagenicities of the b[alpha]a2G and b[alpha]a6A were extremely low, and a totally unexpected result, whereas, those of the bn2G and bn6A were undetectable. CONCLUSION: In this E. coli site-specific mutagenesis system, these bulky aralkylated adducts exhibited no significant mutagenicities, either with or without SOS induction. PMID- 26680919 TI - HER-2/neu in Breast Cancer: Is Consensus Reached in Standard Testing? PMID- 26680920 TI - Passive Smoking and Lung Cancer. AB - Passive smoking is an important risk factor for lung cancer and its impact might be more significant than generally appreciated in Korea. We reviewed the literatures that support the biologic plausibility of Environmental Tobacco Smoke (ETS) causing lung cancer and summarized epidemiological evidences. Because ETS exposure is a preventable risk factor, more social efforts should be directed to reduce ETS exposure. PMID- 26680921 TI - Evaluation of Her-2/neu in Breast Cancer: Comparison of Immunohistochemistry and Polymerase Chain Reaction. AB - PURPOSE: In breast cancer, Her-2/neu amplification/overexpression predicts a poor clinical outcome, and enhanced survival benefits have been reported with Her 2/neu targeted therapy. Currently, there are several methods for assessing the amplification/overexpression of Her-2/neu, each having advantages and disadvantages. The aim of this work was to establish a reproducible, sensitive and specific method of testing for Her-2/neu, which could be used in diagnostic pathology laboratories. MATERIALS AND METHODS: We compared the immunohistochemistry (IHC) detection of Her-2/neu overexpression, with differential polymerase chain reaction (PCR) to assess the gene amplification of the Her-2/ neu, in 163 cases of invasive ductal carcinoma of the breast using paraffin-embedded tissue. In addition, assessment of the appropriate cut off points was established. RESULTS: The overexpression of the Her-2/neu was detected in 39 (23.9%) cases, and its amplification in 37 (22.7%) cases. The methods were positive in 21.5% of cases and negative in 74.8%. There was a 96.3% concordance between the two methods. The sensitivity and specificity of IHC, compared with PCR, were 94.6 and 96.8%, respectively. CONCLUSION: We conclude that the automation of PCR-based Her-2/neu testing approaches is expected to play an increasing role in the future of Her-2/neu testing. Also, we have demonstrated that IHC is a sensitive and specific method for assessing Her-2/neu stati in breast cancer, compared to PCR. The current study indicates that moderate, or strong, complete membrane staining in> or =10% of tumor cells provides an appropriate cut off point compared with PCR. PMID- 26680922 TI - A Clinical Analysis of PTEN Expressions in Breast Cancers. AB - PURPOSE: The PTEN gene, a novel tumor suppressor, is localized to chromosome 10q23.3 and shares extensive homology with the cytoskeletal protein, tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer and Cowden Disease. However, the role of PTEN alterations and its association with clinicopathological factors have not been well established. We investigated the relationship between the PTEN expression and clinicopathological factors. MATERIALS AND METHODS: Formalin-fixed, paraffin embedded tissues from 105 women with breast cancer were evaluated for the PTEN expression and were scored semi-quantitatively based on staining intensity and distribution. RESULTS: were statistically compared with clinicopathological factors. RESULTS: Forty-seven (45%) of the 105 breast cancers had a loss of the PTEN expression. In the recurrent group, 19 of 32 (59%) patients showed a loss of the PTEN expression, whereas in the non-recurrent group, only 28 of 73 (38%) patients showed a loss of the PTEN expression. The loss of PTEN expression correlated with estrogen receptors (ER) (p=0.027), recurrence (p=0.046), HER 2/neu overexpression (p=0.016), disease-free survival (p=0.0163), and overall survival (p=0.0357). In particular, when HER-2/ neu was overexpressed, the overall survival rate correlated with the loss of PTEN expression statistically (p=0.0454), whereas when HER-2/neu was negative, there was no correlation (p=0.9808). Progesterone receptor (PR) and disease stage had no relationship with the PTEN expression. CONCLUSION: Our results support that PTEN plays a role as a tumor suppressor in breast cancer and is a prognostic factor in predicting recurrence. PMID- 26680923 TI - The Prognostic Significance of the Overexpression of HER-2/ neu in Korean Gastric Carcinomas and the In Vitro Effects of Anti-HER-2/neu Antibody on Cell Growth in the Gastric Carcinoma Cell Lines. AB - PURPOSE: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. MATERIALS AND METHODS: We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. RESULTS: p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. CONCLUSION: S: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer. PMID- 26680924 TI - Pilot Study of Heptaplatin, UFT-E and Leucovorin in Advanced Gastric Carcinoma. AB - PURPOSE: Heptaplatin (SKI-2053R, Sunpla ), a new platinum analogue which has a better toxicity profile than cisplatin, has been used with 5-fluorouracil (5-FU) continuous infusion for the treatment of advanced gastric carcinoma. However, continuous 5-FU infusion had a inconvenience to administration. The aim of this study was to evaluate the efficacy and toxicity of heptaplatin, UFT-E and leucovorin combination chemotherapy in advanced gastric cancer. MATERIALS AND METHODS: A total of 22 patients was enrolled in this study at Kyung Hee University and Korea University from September 1999 to May 2001. Heptaplatin 400 mg/m2 was given as intravenous infusion for 1 hour at day 1. Oral UFT-E 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. RESULTS: The 22 enrolled patients received 81 courses of chemotherapy and the median number of course per patient was three with a range of one to six. Five of 21 patients achieved partial responses (23.8%; 95% confidence interval, 5.6% to 42%) without complete response. Out of the 5 responding patients, three had unresectable perigastric lymph-nodes, one patient had a ovarian metastasis, and one patient had a peritoneal metastasis respectively. Main toxicities were neutropenia and nausea/vomiting. Grade 3 and 4 neutropenia were observed in 4 patients (18%) and grade 3 nausea/vomiting were observed in 5 patients (22.7%). The median time to progression was 4 months (range, 0.5 to 13 months), and median survival duration was 7.5 months (range, 2.0 to 14 months). Median response duration was 5.0 months (range, 1.5 to 10 months). CONCLUSION: A combination chemotherapy of heptaplatin, UFT-E and leucovorin has a comparable efficacy with those of previously reported heptaplatin and intravenous regimen of 5-FU and controllable toxicity in advanced gastric carcinoma. Further study with large patient population is warranted to determine the usefulness of this regimen. PMID- 26680925 TI - Infusional 5-Fluorouracil, Leucovorin and Docetaxel in Advanced Gastric Cancer. AB - PURPOSE: This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. RESULTS: The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. CONCLUSION: This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients. PMID- 26680926 TI - Prognosis of Malignant Obstructive Jaundice Following Surgery for Gastric Carcinoma. AB - PURPOSE: Obstructive jaundice is a rare presentation, but is an ominous prognostic sign in patients undergoing surgery for a gastric carcinoma. Therefore, we investigated the prognosis of malignant obstructive jaundice following surgery for a gastric carcinoma. MATERIALS AND METHODS: Thirty-eight patients, with an extrahepatic biliary obstruction due to a metastatic gastric carcinoma, were retrospectively studied to determine their demographics, clinical features, laboratory finding, pathological characteristics and survival. RESULTS: Between January 1996 and April 2000, 2401 patients underwent operations for gastric cancer, of which 38 (1.6%) were found to have obstructive jaundice. The mean age was 55.9 +/- 10.7 years, and the sex ratio (male: female) was 3.2: 1. The median interval between the previous gastrectomy and the presentation of jaundice was 10.1 8.9 months. The levels of total bilirubin and direct bilirubin were 16.5 +/- 6.5 and 12.0 +/- 4.4, respectively. The most common site of the obstruction was the common bile duct (65%). An antrumal location, poorly differentiated stage IV gastric cancer was common associated with obstructive jaundice. A percutaneous transhepatic biliary drainage was a commonly used treatment modality. When the clinical and laboratory findings were presented to a Cox regression analysis, the P values of the time interval and albumin were 0.019 and 0.057, respectively. CONCLUSION: The time interval between a previous gastrectomy, the presentation of jaundice and albumin level were found to be independent risk factors for predicting the survival. PMID- 26680927 TI - Irinotecan Combined with Bolus Fluorouracil, Continuous Infusion Fluorouracil, and Low-Dose Leucovorin Every Two Weeks in Patients with Oxaliplatin Pretreated Metastatic Colorectal Cancer. AB - PURPOSE: To determine the efficacy and tolerance of irinotecan in combination with fluorouracil (5-FU) plus leucovorin (LV) in patients whose disease has progressed after treatment with an oxaliplatin-based therapy. MATERIALS AND METHODS: Thirty-two patients were enrolled in this study from January 2000 to October 2002. Each patient's disease had progressed under oxaliplatin containing regimen. The new treatment consisted of irinotecan 150 mg/m2 as a 90-minute infusion on day 1, LV 20 mg/m2 bolus, given intravenously, immediately followed by a bolus of 5-FU, 400 mg/m2, and a 22-hour continuous infusion at 600 mg/m2 on day 1 through day 2. Treatment was repeated at 2-week intervals. RESULTS: Among the assessable 30 patients, median age was 50 years (range: 29~67), and dominant sites of metastasis were liver, lung, and lymph nodes. The objective response rate was 20%; all patients registered partial responses; 14 patients were stabilized (46.7%); and 10 had progression of disease (33.3%). Median progression free survival was 24.6 weeks and median survival was 39.6 weeks. For the 210 cycles analyzed, NCI-CTC grades 3 and 4 hematologic toxicities were leucopenia (10%) and neutropenia (5%). Frequently occurring grade 3~4 non-hematologic adverse reactions were nausea/ vomiting (10%), diarrhea (6.7%), stomatitis (6.7%), and alopecia (10%). There were no treatment-related deaths. CONCLUSION: S: TIrinotecan in combination with 5-FU plus LV regimen is safe and effective in oxaliplatin-pretreated advanced colorectal cancer patients. PMID- 26680928 TI - Patterns of Failure and Prognostic Factors in Anal Cancer Treated with Radiotherapy. AB - PURPOSE: To analyze the patterns of failure and prognostic factors affecting the local control and survivals in anal cancer treated with definitive radiotherapy, and to find the most effective treatment modality. MATERIALS AND METHODS: Thirty consecutive patients, with primary cancers of the anal canal, were treated using radiotherapy, both with and without 5-FU based concurrent chemotherapy. According to the AJCC tumor stage, six patients hadwere stage I, 11 had stage II, 2 had stage IIIA, and 11 had stage IIIB tumors. The median radiation dose was 45 Gy (30 72 Gy), and with 23 patients receivinged concurrent chemotherapy (5-FU and mitomycin C in 12 patients, 5-FU and cisplatin in 7, and other drugs in 4). The Mmedian follow up period was 43 months, (ranginge, from 8- to 99 months). RESULTS: Among the 1630 patients who16 were treated without surgical resection beforeprior to the radiotherapy, and a complete remission was observed in 12 patients (75%), a partial remission in 3 (19%), and a local progression in the other one patient. The Llocal failures, including persistent disease, were observed in 10 (33%), and the patients with higher T-stages (T3-4) had higher rates of local failure rates (T1-2, 21% vs. T3-4, 72%, p=0.03). Distant metastases were found in 4 patients (13%). The five year survival and disease free survival rates were 64% and 53%, respectively. The factors which affectinged the 5 year local relapse free survival were T-stage (74.9% in T1-2 vs. 28.6% in T3-4, p=0.01), and the existence of a gross tumor beforeprior to radiotherapy (84.6%, no residual vs. 45.1% with residual, p=0.03). CONCLUSION: A Llocal recurrence was the major failure pattern in anal cancers, and the factors affecting a local failure were the T-stage and tumor volume beforeprior to radiotherapy. A Rradiation dose around 45 Gy was sufficient to control tumors of the earlier T stage tumors, but a higher dose should be considered for with more advanced lesions. PMID- 26680929 TI - Differential Sensitivity of Taxol-induced Apoptosis in U2OS and SaOS2 Osteogenic Sarcoma Cells. AB - PURPOSE: Taxol (Paclitaxel) is a new generation of chemotherapeutic drug proven to be effective in the treatment of many cancers. In this study, to further demonstrate the differential effect of the tumor suppressor gene, p53, on the Taxol-induced apoptosis in osteogenic sarcoma cell lines, we used p53-defected SaOS2 cells and wild type p53-expressed U2OS cells. MATERIALS AND METHODS: The cell viability was measured by the XTT assay. To examine whether the differential expressions of p53, in U2OS and SaOS2 cells, were associated with Taxol-induced apoptosis, DNA fragmentation assays were performed on both cytosolic and genomic DNA. Since the cleavage of poly (ADP-ribose) polymerase (PARP) is primarily responsible for apoptosis, the cleavage of PARP, and the expression of cyclin B1, polo-like kinase, Bax, Bcl-xL, Bcl-2 in U2OS and SaOS2 cells were compared by Western blot analyses. RESULTS: The cell viability of the p53-defected SaOS2 cells was markedly decreased with Taxol treatment. Whereas, the cell viabilities due to 6-mercaptopurine and adriamycin were no different between the U2OS and SaOS2 cells. Treatment with Taxol induced a ladder- like pattern of DNA fragments, which is a biochemical hallmark of apoptosis, consisting of multiples of approximately 180-200 base pairs, in a dose-dependent manner in the SaOS2 cells, but insignificantly with the U2OS cells. When the cells were treated with Taxol, the 89 kDa cleavage product of PARP clearly appeared as a function of time in the SaOS2 cells, but not in the U2OS cells. The Taxol-induced apoptosis in p53 defected-osteogenic sarcoma cells was associated with the PARP cleavage as a result of the increased activity of caspase 3, and the high expressions of cyclin B1 and PLK. Bax, as a proapoptotic factor, was increased in the SaOS2cells, but the Bcl-xL and Bcl-2 were decreased when the cells were exposed to 10miceoM Taxol. CONCLUSION: From these results, it was concluded that p53-defected SaOS2 cells are much more sensitive to Taxol-induced apoptosis than p53-expressed U2OS cells. PMID- 26680930 TI - Gene Expression Profiling of Non-Small Cell Lung Cancer. AB - PURPOSE: cDNA microarray provided a powerful alternative, with an unprecedented view scope, in monitoring gene expression levels, and led to the discovery of regulatory pathways involved in complicated biological processes. This study was performed to gain better understanding of the molecular mechanisms underlying the carcinogenesis and progression of lung cancer. MATERIALS AND METHODS: Using a cDNA microarray, representing 4, 600 cDNA clusters, we studied the expression profiles in 10 non-small cell lung cancer (NSCLC) samples and the adjacent noncancerous lung tissues form the same patients. The alterations in the levels of gene expression were confirmed by reverse-transcription PCR in 10 randomly selected genes. RESULTS: Genes that were differently expressed in the cancerous and noncancerous tissues were identified. One hundred and nine genes (of which 68 were known) and 69 cDNAs (of which 32 were known) were up- and down-regulated in>70% of the NSCLC samples, respectively. In the cancerous tissues, the genes related to the cell cycle, metabolism, cell structure and signal transduction, were mostly up-regulated. Furthermore, we identified a few putative tumor suppressor genes that had previously been proposed by other workers. CONCLUSION: S: These results provide, not only a new molecular basis for understanding the biological properties of NSCLC, but also useful resources for the future development of diagnostic markers and therapeutic targets for NSCLC. PMID- 26680931 TI - A Small Cell Lung Cancer Concurrently Diagnosed with Paraneoplastic Dermatomyositis. AB - Dermatomyositis is an inflammatory myopathy, of unknown etiology, which is characterized by cutaneous rashes, accompanied by progressive and symmetric proximal muscle weakness. Especially in older people, the incidences of malignant conditions appear to be increased in dermatomyositis patients, and the prognosis is very poor. Because dermatomyositis may occur as a paraneoplastic syndrome, extensive screening tests, for an occult malignant neoplasm, should be conducted in older dermatomyositis patients. We experienced a case of small cell lung cancer, which had a very rapid and catastrophic clinical course, in a 63-year-old male patient with dermatomyositis. We report this case, and review the literature on the relationship of dermatomyositis and malignancy. PMID- 26680932 TI - M llerian-Type Gland Inclusions in Pelvic Lymph Nodes Mimicking Metastasis: A Case Report and Review of the Literature. AB - Benign lymph node inclusions are rare, and can be mistaken for metastasis. We report, herein, a case of a 50-year-old woman who underwent a hysterectomy, with a lymphadenectomy, for an endometrial carcinoma. There was no lymph node metastasis; however, the left external and common iliac lymph nodes demonstrated a few glands, consistent with M llerian-type inclusions (endosalpingiosis). Awareness of these lesions is important to avoid either unnecessary therapy or any delay in treatment. Furthermore, pelvic and aortic lymphadenectomies may be warranted, as neoplastic transformation of preexisting metaplastic tubal-type epithelium is strongly suggested. This paper presents a case of intranodal endosalpingiosis mimicking metastasis. PMID- 26680933 TI - Cancer Gene Therapy: Limitations and Progress. PMID- 26680934 TI - Treatment of Small Cell Lung Cancer. AB - Among patients with lung cancer, approximately 15% have small cell lung cancer (SCLC), SCLC is usually staged as either limited and extensive. Extensive-stage SCLC is treated primarily with chemotherapy. A recent Japanese randomized trial compared cisplatin and irinotecan (IP) with cisplatin and etoposide (EP). Patients in the IP arm did significantly better than patients in the EP arm. In the IP arm, the response rate was 84%, and the median overall survival period was 12.8 months. Limited- stage SCLC is usually treated with concurrent chemotherapy and accelerated radiation therapy, and approximately 20% of patients are cured. Future research should focus on optimizing chemotherapy regimens and radiation therapy schedules. The role of molecular targeted drugs in the treatment of SCLC must also be evaluated. PMID- 26680935 TI - Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo. AB - PURPOSE: Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns. CONCLUSION: The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line. PMID- 26680936 TI - Development of a Conditional Replication Competent Adenovirus, Controlled by the Human Telomerase Promoter (hTERT). AB - PURPOSE: This study has been planned to generate a replication-competent adenovirus which replicates in a cancer cell-specific manner, thus minimizing the side effects and toxicity of cancer gene therapy. MATERIALS AND METHODS: we have generated an E1B 19 kD attenuated recombinant adenoviruses, Ad-TERT-delta19 and Ad-mTERT-delta19, which encode E1A gene driven by the wild type hTERT and modified m-hTERT promoter containing additional c-myc and Sp1 binding sites in the backbone of Ad-deltaE1B19. The in vitro efficacy and specificity of the hTERT and m-hTERT promoter have been evaluated by the comparison of viral replication and cytopathic effect in cancer cells and normal cell lines. To assess anti-tumor effect and safety of hTERT or m-hTERT promoter driven replication competent adenoviruses, tumor regression after subcutaneous injection in subcutaneous C33A xenografts and lacZ expression after systemic injection in organs were examined. RESULTS: The activation of hTERT or m-hTERT promoter was significantly up regulated only in hTERT-positive cells, but not in hTERT-negative cells. Moreover, the activity of m-hTERT promoter was substantially increased in hTERT positive cancer cells, but not in hTERT-negative cells. While Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect in cancer cells only. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-mTERT-delta19. CONCLUSION: S: The use of m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication competent oncolytic adenovirus under the control of m-hTERT promoter may be a new promising tool for the treatment of human malignancies. PMID- 26680937 TI - Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer: Role as Therapeutic Target. AB - PURPOSE: Increased expression of the hepatocytes growth factor (HGF) receptor (c Met) and urokinase type plasminogen activator (uPA) correlate with the development and metastasis of cancers. However, the mechanisms by which HGF/c-Met signaling mediate cancer progression and metastasis are unclear. Therefore, we investigated the roles of HGF/c-Met in tumor progression and metastasis in pancreatic cancer cell lines, L3.6PL and IMIN-PC2. MATERIALS AND METHODS: To see the functional c-Met protein, we were performed immunoprecipitation for functional c-Met protein. And also performed western bolot analysis and gel zymography for the functional uPA protein. To see the inhibition effects of uPAR monoclonal antibody on invasiveness of two pancreatic cancer cell lines, we were carried out standard two chamber invasion assay. RESULTS: At first, we observed the HGF-mediated c-Met phosphorylation and cell growth. c-Met phosphorylation was increased in the HGF-treated cells in a dose dependent manner. HGF resulted in increments of cell growth and ERK phosphorylation. HGF treatment increased the uPA expression and the uPA activity. A monoclonal antibody 3936, specific to uPAR receptor, inhibited HGF- mediated tumor cell invasion in a dose dependent manner. CONCLUSION: These results suggest that functional c- Met and HGF/c-Met signaling up-regulate the activity of uPA and result in increments of invasion-metastasis in the pancreatic cancer cells. PMID- 26680938 TI - Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study. AB - PURPOSE: Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS: Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement. RESULTS: Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION: This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients. PMID- 26680939 TI - Prognostic Effect of Vascular Endothelial Growth Factor and Angiogenesis in Gastric Carcinoma. AB - PURPOSE: Many studies have shown that angiogenesis has an important role in the growth, progression, and metastasis of solid tumors. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, we investigated the prognostic significance of the expression of VEGF in patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Specimens from 54 gastric adenocarcinoma patients were stained using a polyclonal antibody against VEGF. Correlations of the expression of VEGF, microvessel density, and various other clinicopathological factors were analysed. RESULTS: Seventeen (31.5%) and 37 cases (68.5%) were VEGF-negative and positive, respectively. There was significant correlation between the expression of VEGF and pathological differentiation. There were no significant correlations between the expression of VEGF, stage and recurrence of a gastric carcinoma. The microvessel density was significantly higher in the VEGF-positive than the VEGF-negative tumors. Survivals of the VEGF-negative patients were significantly prolonged compared to those of the VEGF-positive patients. CONCLUSION: The results of this study show that the expression of VEGF may be a useful prognostic factor for patients with a gastric adenocarcinoma. PMID- 26680940 TI - Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer. AB - PURPOSE: Tegafur, an oral prodrug of 5-fluorouracil (5-FU), has been used in the treatment of gastric cancers. UFT (tegafur + uracil) has been developed to enhance the efficacy of tegafur. This study was conducted to assess the pharmacokinetics (PK) of tegafur in gastric cancer patients given the ECU-E regimen (epirubicin, cisplatin, UFT-E, an enteric-coated formula of UFT). A preliminary evaluation of antitumor efficacy and toxicity of ECU-E regimen was also performed. MATERIALS AND METHODS: Of the 32 gastric cancer patients registered for the ECU-E regimen, 8 participated in the PK study. The plasma concentration of tegafur was determined using HPLC. RESULTS: Seven out of the 8 patients were evaluable for response after 2 cycles, and showed 3 partial responses, 1 stable disease and 3 progressive diseases. No major toxicities were observed. Plasma profiles of the tegafur after the first dose showed significant differences in the amount and rate of absorption, i.e., rapid absorption group vs. slow absorption group. The level of C(max) in the rapid absorption group was 1.8 fold higher, and the AUC(0-5h) 4 fold greater, than those in the slow absorption group, nonetheless, the steady state concentrations showed no significant difference. These data indicate that the different absorption rates may not affect the overall exposure to tegafur. The patients with low Cp(ss, peak) showed poor efficacy compared to those with high Cp(ss, peak), suggesting that the concentration of tegafur may be one of the pharmacodynamic determinants in patients administered with ECU-E. CONCLUSION: This study evaluated the pharmacokinetics of tegafur in gastric patients given the ECU-E regimen, and provides preliminary data on the relationship between the plasma tegafur level and the efficacy, which warrants further evaluation. PMID- 26680941 TI - FDG-PET in Mediastinal Nodal Staging of Non-small Cell Lung Cancer: Correlation of False Results with Histopathologic Finding. AB - PURPOSE: Mediastinal staging of non-small cell lung cancer can be markedly improved by FDG-PET scan, but the problem of false staging of mediastinal nodes by PET scan in non-small cell lung cancer has not yet been overcome. The aim of this study was to identify the mechanism underlying the false staging of mediastinal nodes by FDG-PET in the case of non-small cell lung cancer. MATERIALS AND METHODS: To evaluate the factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was performed in 62 patients with NSCLC. GLUT-1 expression was studied by immunohistochemistry of the mediastinal nodes (n=111, true positive 31, true negative 41, false positive 27, false negative 12) using the anti-GLUT-1 antibody. The size, percentage of tumor (tumor ratio), labeling index (rate of stained tumor), staining intensity of the tumor, level of follicular hyperplasia, and staining intensity of the follicle center in the mediastinal node were also studied. RESULTS: There was no significant difference in size among the 4 nodal groups (TP, TN, FP, FN), nor in the tumor ratio of the metastatic nodes between the TP and FN groups. The labeling index and staining intensity of the TP group were higher than those of the FN group (Mann-Whitney test, p=.001, p=.007) in the case of the metastatic nodes. The level of follicular hyperplasia of the FP group was higher than that of the TN group in the case of the non-metastatic nodes (p=.000). CONCLUSION: These results suggest that in mediastinal staging of non-small cell lung cancer by FDG-PET, the FN node is associated with low uptake of FDG due to low expression of GLUT-1, and that the FP node is associated with a high level of follicular hyperplasia as a result of there being a reactive change to an inflammatory and/or immune reaction. This is the first report on the mechanism underlying the false results that are sometimes obtained, and which constitute a major problem in the clinical application of FDG-PET to the mediastinal staging of non-small cell lung cancer. PMID- 26680942 TI - A Phase II Study of Paclitaxel and Cisplatin Combination Chemotherapy in Advanced Non-small-cell Lung Cancer. AB - PURPOSE: Paclitaxel and cisplatin, active drugs in the treatment of non-small cell lung cancer (NSCLC), have been found to be synergistic and less myelotoxic in combination when the paclitaxel is given 24 hr prior to the cisplatin. Their antitumor activity and toxicity in patients with advanced NSCLC has been evaluated herein. MATERIALS AND METHODS: Seventy-four chemonaive patients, with advanced NSCLC, were enrolled. Paclitaxel, 175 mg/m2, was administered on day 1, followed 24 hr later by cisplatin, 75 mg/m2, on day 2. RESULTS: The overall response rate, median time to progression and median survival time were 51%, 7.1 months (95% confidence interval (CI), 5.5~8.7 months) and 13.7 months (95% CI, 11.3~16.1 months), respectively. There were significant differences in the overall survival rates in relation to stage and the ECOG performance status(PS). The toxicity was mainly nonhematological. Grade > or =3 neuropathy occurred in 2 (3%) patients, myalgia in 3 (4%), and bone pain in 3 (4%). The hematological toxicity was mild, and no grade 3 or 4 neutropenia was observed. CONCLUSION: The combination of paclitaxel and cisplatin is an effective and tolerable treatment regimen for advanced NSCLC during first line chemotherapy. The main toxicity was nonhematological, such as peripheral neuropathy, myalgia and bone pain, whereas the hematological toxicity itself was mild. PMID- 26680943 TI - Clinical Features of Pulmonary Large Cell Neuroendocrine Carcinoma. AB - PURPOSE: This study was performed to investigate the clinical features of large cell neuroendocrine carcinomas (LCNEC). MATERIALS AND METHODS: We retrospectively reviewed the histopathology and clinical information of 37 patients with LCNEC, diagnosed between June 1992 and May 2002 at the Severance Hospital, and performed immunohistochemical (IHC) staining. RESULTS: The prevalence of LCNEC among primary lung cancers was 0.3%, 37 out of 13, 012 cases over a 10 year period. The mean age was 61+/-12 years old, with 34 (92%) males and 3 (8%) females. 30 patients smoked, with an average of 42 packs per year. A cough was the most frequent symptom. The tumor was located at the periphery of the lung in 24 cases (65%). Among the 30 cases that underwent surgery, 4 were diagnosed pathological stage IA, 11 IB, 1 IIB, 13 IIIA and 1 IIIB. The 7 clinically non-operable cases were IIIB in 3, and IV in 4. The positive rates of CD56, thyroid transcription factor-1 (TTF-1), chromogranin A, synaptophysin and 34betaE12 for tumor cells were 88.9, 55.6, 42.1, 31.6 and 21.1%, respectively, from the IHC staining. The median survival time and 5 year-survival rate were 24 months and 27%, respectively. The group that underwent surgery had a better prognosis than those that did not. CONCLUSION: The positive rates for the tumor markers varied, but those of the CD56 and TFT-1 were the highest. The possibility of LCNEC needs to be evaluated for the following situations: small cell carcinomas located at the periphery and not responding chemotherapy, small cell carcinomas diagnosed by percutaneous needle aspiration, poorly differentiated non-mall cell carcinomas, with uncertain histologic type, and unclassified neuroendocrine tumor, etc. PMID- 26680944 TI - Detection of p16(INK4A) in the Mixed Cell Populations of Normal Peripheral Blood Mononuclear Cells and Cervical Cancer Cell Lines. AB - PURPOSE: Human papilloma viruses (HPVs) play a central role in the pathogenesis of neoplastic lesions of the uterine cervix. The viral oncoprotein HPV E6 degrades the p53 protein, and the HPV E7 protein inactivates pRB and increases the expression of the CDK inhibitor, p16(INK4A). We investigated the usefulness of p16(INK4A) as a biologic marker for the cervical dysplastic and neoplastic cells. MATERIALS AND METHODS: We examined the expression of p16(INK4A) and cytokeratin in a mixed population of normal peripheral blood mononuclear cells (PBMC) and the cervical cancer cell lines (HeLa, SiHa, and CasKi) using flow cytometry. RESULTS: The DNA indices of the HeLa, SiHa and CasKi cell lines were 1.89, 1.53 and 1.75, respectively, indicating that these cells are aneuploid cells. Furthermore, the positive rate of p16(INK4A) expression was 86.7% for the HeLa mixed population, 85.6% for the SiHa mixed population, and 92.2% for the CasKi mixed population. According to the FL3A vs FL3W histogram, electrical gating of the HeLa, SiHa and CasKi mixed populations showed the expression levels of both cytokeratin and p16(INK4A) to be identical, at 86.6%, 84.8% and 85.0%, respectively. These findings revealed that almost all cells selected through electrical gating were cervical cancer cells originating from the epithelium and which expressed cytokeratin and p16(INK4A). On the other hand, when each mixed population was electrically gated for normal PBMC, we found that the PBMCs expressed neither cytokeratin nor p16(INK4A). CONCLUSION: Using flow cytometry, we observed the enhanced expression of p16(INK4A) in cervical cancer cell lines. These. RESULTS: suggest the usefulness of p16(INK4A) for the selective detection of cervical dysplastic and cancer cells in the liquid-based samples, which are taken from the cervices and contaminated with blood and stromal cells. PMID- 26680945 TI - Docetaxel and Cisplatin Combination Chemotherapy in Patients with Squamous Cell Carcinomas of the Head and Neck. AB - PURPOSE: The objective of this phase II study was to assess the clinical antitumor activity and toxicities of docetaxel and cisplatin chemotherapy, in patients with locally advanced and metastatic, recurrent squamous cell carcinomas of the head and neck (SCCHN). MATERIALS AND METHODS: All eligible patients with locally advanced and metastatic, recurrent SCCHN had received two courses of chemotherapy followed by repeated head and neck examinations and computed tomography. Patients who had received prior chemotherapy with taxanes were ineligible. If the patients achieved a response (either CR or PR), they received one more course of chemotherapy prior to undergoing definitive local treatment. The combination chemotherapy consisted of docetaxel, 70 mg/m2, and cisplatin, 75 mg/m2, on day 1, with the cycles repeated every 3~4 weeks. RESULTS: All 32 patients were assessable for response and toxicity analyses. The most common grade 3/4 adverse event was neutropenia, which occurred in 11% of cases. No febrile neutropenia was noticed. The other grade 3/4 adverse events included: anemia (2%) and stomatitis (3%). The response rate in patients with locally advanced cancer was 19/21 (90%). Fifteen patients (71%) achieved a CR and 4 (19%) a PR. Out of the 4 patients presenting with a distant metastatic disease, 1 each achieved CR and PR, with 2 stable disease (SD). Out of the 7 patients with a recurrence at a distant site, 1 each achieved PR and SD, and 5 (71%) had a progression of the disease (PD). The overall response rate was 22/32 (69%). CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable toxicity profile. This regimen may offer high antitumor activity on short outpatient administration, with a low incidence of severe toxicity. PMID- 26680946 TI - Paclitaxel and Cisplatin Combination Chemotherapy in Pretreated Breast Cancer. AB - PURPOSE: A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy. PMID- 26680947 TI - Second-Line Chemotherapy for Advanced Non-small Cell Lung Cancer: Past, Present, and Hope for the Future. PMID- 26680948 TI - Advances in Nuclear Oncology. PMID- 26680949 TI - Microsatellite Alterations in Serum DNA of Lung Cancer Patients. PMID- 26680950 TI - Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non Small Cell Lung Cancer. AB - PURPOSE: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy. PMID- 26680951 TI - Effect of Combination Chemotherapy with Docetaxel Plus Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: This study was conducted to evaluate the efficacy and safety of combination chemotherapy, with docetaxel and cisplatin, as a first line treatment for advanced non-small cell lung cancer. MATERIALS AND METHODS: Between March 1998 and December 2001, 35 patients with advanced non-small cell lung cancer were enrolled in this study. The patients were treated at 3-week intervals, with one course of a regimen consisting of docetaxel (75 mg/m2 IV for 1 hours) on day 1 and cisplatin (60 mg/m2 IV) on day 2. RESULTS: The median age of the patients was 60.3 years. Of the 35 patients, 20 and 15 had stage IIIb and stage IV diseases, respectively. A complete response was observed in 1 patient and partial response in 15, with an overall response rate of 46%. The overall median survival duration was 40.3+/-25.2 weeks. The median time to progression and response duration were 21.6+/-5.5 and 15.1+/-5.9 weeks, respectively. The survival duration was statistically significantly longer in the response group (50.6 weeks) than in the non-response group (31.6 weeks) (p<0.05). Of the hematological side effects, grades III and IV leukopenia were observed in 4.8% of patients. Grades III and IV nausea and vomiting were observed in 48.5%, and grades I and II neuropathy in 11.4% of the treated patients. These toxicities were well tolerable and reversible. There were no hypersensitivity reactions. CONCLUSION: Docetaxel and cisplatin combination chemotherapy is relatively effective and safe in advanced non-small cell lung cancer patients. PMID- 26680952 TI - New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology. PMID- 26680953 TI - Alterations in Promoter Usage and Expression Levels of Insulin-like Growth Factor II and H19 Genes in Cervical and Endometrial Cancer. AB - PURPOSE: The biallelic expression of insulin-like growth factor-II (IGF2) and H19 has been reported to be associated with the progression of several tumors. Here, the promoter usage and expression levels of IGF2 and H19 are reported to be altered in cervical and endometrial cancers showing loss of imprinting (LOI). MATERIALS AND METHODS: The imprinting status of IGF2 and H19 was examined in 32 cervical carcinomas, their matched normal tissues, 13 endometrial cancer and 33 normal endometrial tissues. RESULTS: The LOI of IGF2 was observed in 7 of 18 (39%) and 1 of 13 (8.3%) informative cervical carcinomas and informative endometrial cancers, respectively. The LOI of the H19 gene was detected in 5 of 14 (36%) and in all 11 (100%) informative cervical carcinoma cases and informative endometrial cancer cases, respectively. The use of promoter P1 was observed in the LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2 imprinting (MOI), or in cervical and endometrial cancers. Unlike MOI tumors, some LOI tumors revealed a lack of IGF2 transcription from the promoter P3. The LOI tumors of IGF2 showed increased expression of the IGF2 level, but a down regulation of the H19, relative to normal tissues, whereas the MOI tumors revealed no significant alterations. CONCLUSION: These results suggest that the promoter P1 could be involved in the biallelic expression of IGF2, and that the altered expression of the IGF2 and H19 levels might be associated with the progression of cervical and endometrial cancers that exhibit biallelic IGF2 expression. PMID- 26680954 TI - Prognostic Significance of KAI-1 and Survivin Expressions in Ovarian Epithelial Carcinomas. AB - PURPOSE: The purpose of this study was to evaluate the expressions of KAI-1 and survivin, and to investigate their correlation with the clinical stage and survival rate of patients with ovarian carcinomas. MATERIALS AND METHODS: The expressions of survivin and KAI-1 were immunohistochemically determined in 54 serous and mucinous ovarian adenocarcinomas and borderline malignancy tumors. 10 of the 54 cases were also analyzed for the expressions of survivin and KAI-1 using western blot. RESULTS: The down-regulation of the expression of KAI-1 was observed by immunohistochemical staining (IHC) in 53.7% of the ovarian cancers, and a negative reaction in 50% by the western blot analysis. From the IHC, the survivin expression was positive and strongly positive in 51.9 and 18% of the ovarian cancers, respectively. From the western blot analysis, 10% of the ovarian cancer showed positive reactions. The down- regulation of the KAI-1 expression was significantly correlated with the clinical stage (p=0.001) and disease free survival rate (p<0.001), but not with the histological type. The expression of survivin was not correlated with the clinical stage or histological type. However, the patients with a negative survivin expression had a significantly longer disease survival rate than those with a strong positive expression. CONCLUSION: The down- and up-regulation of the KAI-1 and survivin, respectively, might be independent prognostic factors in human ovarian carcinomas. PMID- 26680955 TI - Concurrent FP (5-fluorouracil, cisplatin) Chemoradiotherapy for Patients with Esophageal Cancer. AB - PURPOSE: The outcomes of a surgical approach for patients with an esophageal carcinoma remain unsatisfactory despite its high complication rates. We conducted a phase II trial, using combined FP (5-fluorouracil and cisplatin) chemotherapy and concurrent radiotherapy, as a definitive therapy for patients with esophageal cancer. MATERIALS AND METHODS: Patients with histologically proven esophageal cancer were enrolled onto this study. The treatment consisted of four courses of chemotherapy and six and a half weeks of radiotherapy. The patients received chemotherapy in weeks 1, 5, 12 and 16 (5-fluorouracil 1, 000 mg/m2 on days 1 to 4 and cisplatin 75 mg/m2 on day 1). Radiotherapy was administered at a dose of 59.4 Gy, in five 1.8 Gy fractions a week. RESULTS: A total of 22 eligible patients entered the study. Of the 19 evaluable patients, a complete response occurred in 7 (37%), and a partial response in 8 (42%). After a median follow-up of 35 months, the overall survival rate was 32% at three years and the median survival was 11 months. Fourteen (64%) received planned dose of radio-therapy and 13 (59%) received more than three courses of chemotherapy. However, there was no difference in three-year survival rates between the patients that received less than three courses of chemotherapy and those that received three or more courses (31% vs. 32%). The major treatment related toxicity was mucositis, which developed in every patient, with grades III or IV in thirteen (59%) patients. During the treatment, the patients lost, on average, 3.8% of their body weight. The mean hospital stay was 23 days, with a total duration of treatment of 74 days. CONCLUSION: S: Concurrent FP chemoradiotherapy was effective as a definitive therapy for patients with esophageal cancer. The major toxicity was mucositis. Although the treatment was relatively feasible, a randomized trial of reduced courses of chemotherapy is warranted. PMID- 26680956 TI - Clinical Significance of the Levels of Serum Cholesterol in Patients with Gastric Cancer. AB - PURPOSE: The relationship between serum cholesterol levels and mortality is complex. Serum cholesterol levels correlate positively with coronary artery disease, but some studies have suggested a negative relationship in cancer patients. Because the serum cholesterol levels are one of the most frequently assayed laboratory values, trends in the levels of cholesterol were investigated, in patients with gastric cancer and assumed a possible role in cancer screening. MATERIALS AND METHODS: The serum cholesterol levels were retrospectively analyzed in a group of 220 patients, diagnosed with gastric cancer, and in 177 healthy subjects. Anthropometric (body mass index: BMI) and biochemical indices of their nutritional status were also determined in the study subjects. Statistical analyses were performed by analyses of variance and covariance, and a discriminant analysis. RESULTS: The levels of serum cholesterol, albumin, Hb and the BMI were significantly lower in the gastric cancer-patients group than in the healthy-subjects group. The serum cholesterol and Hb levels were shown to be independent of each other, when adjusted for the effects of the BMI. In the patients with gastric cancer the levels of cholesterol and Hb showed decreasing tendencies as did the tumor extension, as defined by the TNM system. CONCLUSION: The serum cholesterol and Hb levels were significantly lower in patients with gastric cancer than in the healthy subjects, which seemed to be linked to the progression of gastric cancer. Therefore, further study is required for the serum cholesterol and Hb levels to be used as markers in cancer screening and its progression, in patients with gastric cancer. PMID- 26680957 TI - TRAIL-Mediated Apoptosis in Human Liver Chang Cells. AB - PURPOSE: Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL)/APO-2L is a member of the TNF family that can kill a wide variety of tumor cells, but not normal cells. This study was designed to investigate the down stream target proteins in TRAIL-mediated apoptosis of human liver, Chang cells. MATERIALS AND METHODS: The expressions of DR4/DR5 in hepatoma cells, including Chang, HepG2 and Hep3B cells, were determined by RT-PCR. Cell viability was measured by MTT assay and apoptosis was assessed by DNA fragmentation assay. The catalytic activity of caspase- family proteases, including caspase-3 and -9, was tested by using fluorogenic biosubstrates. Expression of apoptotic mediators, including procaspase-3 and PARP proteins, was measured by Western blotting. The expression profile of proteins in Chang cells by using two-dimensional (2-D) gel electrophoresis and MALDI-TOF. RESULTS: The results demonstrated that TRAIL (100 ng/ml) induced the apoptotic death of Chang cells, as characterized by the ladder pattern fragmentation of genomic DNA. TRAIL increased the enzymatic activity of caspase- 3, corresponding to the time of appearance of cleaved PARP and caspase 9. In 2-D gel electrophoresis and MALDI- TOF analysis, the comparison of control versus apoptotic cells in the protein expressions revealed that signal intensity of 7 spots were decreased, whereas 6 spots were increased among 300 spots. These spots were resolved and identified as a protein information by MALDI-TOF. CONCLUSION: We suggested that TRAIL induces the apoptotic death of Chang cells via proteome alterations inducing caspase cascade. PMID- 26680958 TI - Clinical Value of Whole Body F-18 FDG PET in The Management of Recurrent Colorectal Malignancy. AB - PURPOSE: The aim of this study was to evaluate the clinical value of whole body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the patient with a recurrence of a previously treated colorectal malignancy. MATERIALS AND METHODS: Fifty-eight cases were scanned using PET at the PET Center of Seoul National University Hospital between May 1995 and Aug 2002. All the patients had had a previous operation for a colorectal malignancy. The PET scans were performed for the following reasons: - investigation of a recurrence (n=12), investigation of the operability (n=38) and clinical follow up (n=8). In these 58 cases, 47 of the CT scans and 55 of the CEA (Carcinoembryonic antigen) were checked prior to the FDG- PET. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET scans were calculated, and compared with those of conventional CT scan and CEA, which were also compared with the previous reported data. Eight cases, whose managements were influenced by the PET findings, were analyzed. RESULTS: Recurrences, or metastases, of colorectal cancer developed in 51 cases, with 49 of these being detected by the PET. The accuracy, sensitivity and specificity of the PET were 96.6 (56/58), 96.1 (49/51) and 100% (7/7), respectively. The PPV and NPV of the PET were 100 (49/49) and 77.8% (7/9), respectively. The accuracy and sensitivity of the PET were higher than those of the CT (85.1 and 88.1%), with the differences being statistically significant (p-value 0.001 and 0.003, respectively). CONCLUSION: It is concluded that a FDG-PET scan is a more accurate and sensitive diagnostic tool than a CT scan for the detection of a recurrence or metastasis in a colorectal malignancy. In addition, a FDG-PET may alter the management of patients with recurrent colorectal cancer. Therefore, it is recommended that a PET should be considered when a tumor recurrence is suspected during conventional follow up. PMID- 26680959 TI - The Expressions of Cytokeratin 7 and 20 in Epithelial Tumors: A Survey of 91 Cases. AB - PURPOSE: This study was performed to determine the expressions of cytokeratin 7 and cytokeratin 20 in epithelial neoplasms, and to investigate their potential role in the differential diagnosis of carcinomas of various organs. MATERIALS AND METHODS: We investigated 91 various cases of primary and metastatic cancers, using a panel of commercially available monoclonal antibodies against cytokeratins 7 and 20 (CK7 and CK20), by immunohistochemistryand an avidin-biotin immunoperoxidase technique. The specimens were formalin-fixed and paraffin- embedded, and examined using 4micrometer thick serial sections. RESULTS: The expression of CK7 was seen in the majority of carcinoma cases, including transitional cell carcinomas (100%), pulmonary adenocarcinomas (100%), ovarian serous adenocarcinomas (100%), cholangiocarcinomas (70%), colonic adenocarcinomas (64.29%) and invasive ductal carcinomas (60%). The expression of CK20 was seen in the majority of colorectal carcinomas cases (85.72%), but was virtually absent in pulmonary adenocarcinomas (0%), uterine cervical carcinomas (0%), ovarian carcinomas (0%), prostatic adenocarcinomas (0%), adenocarcinomas of the gall bladder (0%) and cholangiocarcinomas (12.5%). CONCLUSION: In the all cases investigated, either CK7 or CK20 immunophenotypes were conserved in the tumor cells of primary tumors and in those of the corresponding metastatic lesions. It is suggested that CK7/CK20 immunophenotyping, in metastatic carcinomas of an unknown origin, maybe useful in the determination of the primary site of the metastasis. PMID- 26680960 TI - Metastatic Anaplastic Carcinoma of the Small Intestine Arising from The Lung. AB - A metastatic carcinoma of the small intestine is rare. Here, the case study of an 80-year-old lung carcinoma patient, with generalized peritonitis due to neoplastic perforation of the small intestine is reported. Pathological studies of a small intestinal mass revealed a metastatic anaplastic carcinoma arising from the lung. Patients with known lung carcinoma, who develop abdominal complaints, should be examined thoroughly. Although it is very difficult to diagnose and treat a metastatic carcinoma of the small intestine, in our judgment, with a greater awareness of this neoplasm, more cases may be diagnosed in the early stages, leading to improved rates of survival. PMID- 26680961 TI - Does the Addition of Adjuvant Chemotherapy to Concurrent Chemoradiotherapy Improve the Survival of Patients with Locally Advanced Nasopharyngeal Cancer? PMID- 26680962 TI - Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer. AB - The majority of non-small cell lung cancer patients present with locally advanced disease that may not be resectable. A single modality treatment such as thoracic radiotherapy often results in an inferior outcome when compared to combined modality treatment. Various combinations of radiotherapy, chemotherapy, and surgery have been tested in patients with locally advanced non-small-celllung cancer with promising results. The favorable results of the combined modality treatment are accompanied by a corresponding increase in treatment related morbidity. In this article, the results of the application of combined modality treatments in the management of locally advanced non-small cell lung cancer are reviewed. PMID- 26680963 TI - Stomach Cancer Incidence, Mortality and Survival Rate in Korean Elderly Pharmacoepidemiologic Cohort (KEPEC) in 1994~1998. AB - PURPOSE: This study was conducted to estimate the incidence, mortality and survival rate of stomach cancer in elderly people in Korea. MATERIALS AND METHODS: The source population was a Korean Elderly Phamacoepidemiologic Cohort (KEPEC), who were 65 years of age or older and living in Busan metropolitan city and Gyeongsangnam province, Korea. A subcohort of 38, 443 persons without stomach cancer were identified before enrolling the KEPEC. The stomach cancer incidence cases were detected from three different sources, the medical claims database of the Korea Medical Insurance Corporation (KMIC), the Korea Central Cancer Registry (KCCR), and the Busan Cancer Registry (BCR). A hospital survey for abstracting the relevant information to confirm the final diagnosis of the potential cases from the medical claims database was conducted. A medical oncologist reviewed the data to confirm the final diagnoses and the date of onset. The mortality cases due to stomach cancer were detected from the mortality database at the National Statistical Office. The incidence rate, the survival rate and the mortality rate of stomach cancer and their 95% confidence intervals were estimated using SAS Windows ver. 8.1. RESULTS: There were 338 confirmed stomach cancer cases in the KEPEC between 1 January 1994 and 31 December 1998. The age-standardized incidence rate of stomach cancer in the Korean elderly population was estimated to be 351.4 per 100, 000 person-years in males and 122.6 per 100, 000 person-years in females. In addition, 272 stomach cancer death cases were detected in the KEPEC between 1 Jan. 1994 and 31 Dec. 1998. The age-standardized mortality rate of stomach cancer to the Korean elderly population was estimated to be 268.5 per 100, 000 person-years in males and 93.7 per 100, 000 person-years in females. The one-year survival rate was 62.1% in males and 63.0% in females, which was considered to be statistically similar. The three-year survival rate was 38.9% in males and 40.9% in females. The five-year survival rate was 34.8% in males and 34.7% in females. CONCLUSION: The age-standardized male stomach cancer incidence rate and mortality rate to the Korean population were approximately three times higher than in female. However, there was little significant difference between males and females in terms of the overall survival rates. These results may be useful for planning a health policy for preventing and managing stomach cancer in Korea. PMID- 26680964 TI - High Dose Radiation Therapy Concurrent with Chemotherapy in Locally Advanced Nasopharynx Cancer. AB - PURPOSE: Here, our results from a prospective treatment protocol of concurrent radiochemotherapy (CRCT), which was conducted for locally advanced nasopharynx cancers, between April 1994 and May 2001, are reported. MATERIALS AND METHODS: A total of 52 consecutive eligible patients were accumulated for this protocol. The median radiation doses to the primary site, involved nodes and uninvolved neck were 72, 61.2 and 45 Gy, using a serial shrinking field technique. The boost techniques were 3-dimensional conformal radiation therapy in 45, intracavitary brachytherapy in 3 and 2-dimensional radiation therapy, with multiple small fields, in 2 patients. Two chemotherapy regimens were used: the first regimen, used in 8 patients during the earlier part of the study duration, consisted of 2 cycles of cisplatin plus 5- fluorouracil every 4 weeks, with concurrent radiation therapy, and 4 cycles with the same agents every 4 weeks, adjuvantly; the second regimen, used in 44 patients during the later part, consisted of 3 cycles of cisplatin every 3 weeks, with concurrent radiation therapy and 3 cycles of adjuvant cisplatin plus 5-fluorouracil every 3 weeks. RESULTS: The median follow up period of the survivors was 32 months. The male to female ratio was 36/16, with a median age of 48 years. The stages, according to the new AJCC staging system (1997), were IIb in 6, III in 23, IVa in 14 and IVb in 9 patients. Fifty and 32 patients completed the planned radiation therapy and concurrent chemotherapy, respectively. Two patients died, 1 of septic shock during the CRCT and the other of malnutrition during the adjuvant chemotherapy. There were 12 failures in 11 patients: 7 locoregional recurrences, 1 within and 6 outside the radiation target volume, and 5 distant metastases. The locoregional control, disease-free survival and overall survival rates were 84.3, 78.8 and 92.8% at 3 years, respectively. CONCLUSION: High dose radiation therapy, coupled with concurrent chemotherapy, was judged a highly effective treatment for locally advanced nasopharynx cancers. PMID- 26680965 TI - Expression of Cyclooxygenase-2 and Tumor Microvessel Density in Colorectal Cancer. AB - PURPOSE: The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of human cancer. This study investigated the COX-2 expression in colorectal cancer, and its relationships with tumor angiogenesis and the clinicopathological factors. MATERIALS AND METHODS: The expression of the COX-2 protein and microvessel density were evaluated, using immunohistochemical methods, in 21 normal colonic mucosa and 190 human colorectal carcinomas. Correlations between COX-2 expression and microvessel density, as well as various clinicopathological factors, were studied in colorectal carcinomas. RESULTS: The COX-2 protein expression in epithelial cells was increased in 169 of the 190 adenocarcinoma cases (88.9%), but in only 1 of the 21 (4.8%) normal mucosa cases. The COX-2 expression was significantly increased in the differentiated compared with the undifferentiated colorectal carcinomas (p<0.05), and significantly correlated with the depth of invasion and microvessel density (p<0.05). Rectal cancers had more COX-2 positive cases than the colon cancers (p<0.05). However, there were no significant differences in the tumor size and the presence of lymphatic or vascular invasion. CONCLUSION: The overexpression of cyclooxygenase-2 in colorectal carcinomas seems to play a role in the invasion and angiogenesis of the tumors, so may be a useful marker of the prognosis. The prominent expression was also demonstrated in differentiated colorectal cancers. PMID- 26680966 TI - Combination Chemotherapy of Oxaliplatin and Capecitabine in Patients with Metastatic Colorectal Cancer: a Pilot Study. AB - PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin and capecitabine in patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between December 2001 and April 2003, fourteen patients were enrolled in this study. Oxaliplatin, 80 mg/m(2), was administered intravenously on day 1, and capecitabine, 1, 250 mg/m(2) bid po (total daily dose 2, 500 mg/m(2)), was given on days 1~14 of 3 week cycles. RESULTS: The median age of the patients was 57 years (range: 41~74), and the most common sites of metastasis were liver, lung or lymph node. Of the 12 evaluable patients, the overall response rate was 41.7%, but with no complete response. The median response duration and median progression free survival of 12 patients were 42 and 24.4 weeks, respectively. The median overall survival was not reached. A median 6 (range: 1~9), and a total 80, cycles were administered to 14 patients. 80 cycles were evaluable for toxicity. The most common hematological toxicities were NCI grades I/II anemia (45%), leucopenia (33.75%) and thrombocytopenia (17.5%). The most common non hematological toxicities were nausea/ vomiting (28.75/5%) and neurotoxicity (8.75%). Hand and foot syndrome was noted in only 3.75%. There was no life threatening toxicity. CONCLUSION: Oxaliplatin and oral capecitabine combination chemotherapy showed significant activity and favorable toxicity in patients with metastatic colorectal cancer. Further studies, with larger numbers of patients and long-tern follow-up will be needed. PMID- 26680967 TI - Associations between Depression, Anxiety, Hostility and Fighting Spirit among Cancer Patients in a Cancer Center in Korea. AB - PURPOSE: The aim of this study was to examine the associations between depression, anxiety, hostility and fighting spirit among patients with stomach, colorectal or breast cancer. MATERIALS AND METHODS: 223 patients, diagnosed as with stomach, colorectal or breast cancer, undergoing chemotherapy or follow up care, were the subjects of the study. The study design was cross-sectional at the time of the survey. The degrees of depression, anxiety and hostility of the patients were assessed by the SCL-90-R scores, and the fighting spirit was measured by the Mental Adjustment to Cancer (MAC) scale score. RESULTS: The scores of anxiety and hostility of the patients at younger age were higher than those at older age (p<0.01). The patients with metastasis were more depressed than those without it (p<0.01). There was a negative association between depression and fighting spirit (p<0.001). CONCLUSION: The study showed the more depressed cancer patients had lower fighting spirit score, which was known to be one of the most active psychosocial contributors in adjusting to cancer and survival. PMID- 26680968 TI - Expression of the Low Molecular Weight Cyclin E is Early Event in Colorectal Carcinogenesis. AB - PURPOSE: Cyclin E is essential for the transition from the G1 to S-phase of the cell cycle, and plays important roles in carcinogenesis in many cancers. Especially, low molecular weight cyclin E is overexpressed in breast cancer and its level of expression correlates well with the progression and prognosis. Although the cyclin E level is amplified, and overexpressed, in many cancers, including colorectal cancer, the role of low molecular weight cyclin E in colorectal cancer remains to be studied. Therefore, the expression of low molecular weight cyclin E in various stages of colorectal tumors was studied. MATERIALS AND METHODS: The expression of low molecular weight cyclin E was analyzed in 45 tumors, and compared with paired normal mucosa from the same patients (6 adenomas, 11 stage A, 14 stage B and 14 stage C colorectal cancers) by Western blot analysis. The expres sion of low molecular weight cyclin E was also analyzed in normal colon mucosa from 12 healthy normal controls. RESULTS: The low molecular weight cyclin E was expressed exclusively in all stages of colon tumors, but not in the normal mucosa from the same patients or in the normal controls. However, there was no correlation between tumor progression and the degree of expression of low molecular weight cyclin E. CONCLUSION: The expression of low molecular weight cyclin E is suggested to be an early event in colorectal carcinogenesis. PMID- 26680969 TI - Increased Cytopathic Effect of Replicating Adenovirus Expressing Adenovirus Death Protein. AB - PURPOSE: Replication-competent adenoviruses (Ads) are promising new modalities for the treatment of cancer. Selective replication of a viral agent in tumor may lead to improved efficacy over non-replicating Ads due to viral multiplication, lysis of the infected cancer cell and spread to surrounding cells. In our previous studies it was shown that the E1B 55 kD-deleted Ad (YKL-1) exhibits tumor specific replication and cell lysis, but with reduced cytolytic effects compared to the wild type adenovirus (Int J Cancer 2000;88: 454-463). Thus, improving the potency of oncolytic Ads remains an important goal for cancer gene therapy. To increase the oncolytic ability of YKL-1, an adenovirus death protein (ADP) gene was reintroduced under the control of a CMV or MLP promoter at the E3 region of the YKL-1, generating an YKL-cADP and YKL-mADP, respectively. MATERIALS AND METHODS: The in vitro cytolytic effect of ADP expressing Ads was evaluated by MTT assay, and the induction of apoptosis by ADP expressing Ads was examined by TUNEL analysis. Finally, the antitumor effect of ADP expressing Ads was demonstrated in C33A xenograft tumor model. RESULTS: The YKL-cADP exerted a markedly enhanced cytolytic effect against H460 and SK-Hep1 cancer cell lines. The TUNEL assay indicated that the ADP-mediated cytotoxicity was largely driven by apoptosis. Finally, the YKL-cADP showed a superior antitumor effect than the YKL-1 or YKL-mADP in C33A xenografts. CONCLUSION: These lines of evidence demonstrate that the YKL-cADP induces efficient cell lysis, which is critical for the addition of therapeutic value to replicating Ads in cancer gene therapy. PMID- 26680970 TI - Lack of Association between Epstein-Barr Virus and Epithelial Malignancies Developed after Kidney Transplantation. AB - PURPOSE: Organ transplant recipients are at high risk of developing malignancies due to immunosuppressive regimens. Unlike post-transplant lymphoproliferative diseases (PTLDs), where Epstein-Barr virus (EBV) plays an etiological role, there are conflicting data regarding the association of EBV with post-transplant epithelial malignancies. In order to clarify the role of EBV in carcinomas that develop after solid-organ transplantation, the presence of EBV infection in the carcinomas of post-kidney transplant patients was examined. MATERIALS AND METHODS: The presence of EBV infection in skin carcinoma (PTSC), gastric carcinoma (PTGC) and urothelial carcinoma (PTUC), which developed in the patients under an immune suppression regime following kidney transplantation, was examined. Tumors from the patients without organ transplantation were also used as a comparison in the study. The study group included five nasopharyngeal carcinomas (NPCs), one Hodgkin's disease (HD), one B-cell non-Hodgkin's malignant lymphoma (NHL) and one hypopharynx (HPC) tumor. RESULTS: Immunofluorescence assay and Western blot analysis, using sera from the same patients, confirmed that all of the tested patients were previously infected with EBV. From in situ hybridization, no EBER positive cells were detected in any of the tumor tissues obtained from the three kidney transplant recipients (PTSC, PTGC and PTUC) or in the NHL and HPC tissues. In contrast, all five of the NPC and HD tissues showed strong EBER positivity. CONCLUSION: These results suggest that there is a strong association of EBV with NPC and HD as previously reported, while no such strong association of EBV was found with epithelial malignancies that developed after kidney transplantation. PMID- 26680971 TI - Clinical Implications of VEGF and p53 Expression in Squamous Cell Carcinoma of the Cervix Treated with Radiation Therapy. AB - PURPOSE: The present study was designed to analyze the relationship between vascular endothelial growth factor (VEGF) and p53, and their impact on clinical outcome in squamous cell carcinoma of the cervix treated with radiation therapy. MATERIALS AND METHODS: This immunohistochemical study involved 23 patients with available paraffin blocks among 46 patients who were treated during the period from 1994 to 1997 in Eulji University Hospital in Korea. Anti-VEGF mouse monoclonal antibody and DO-7 anti- p53 mouse monoclonal antibody were used as the primary antibodies. Antibody binding was detected with a LSAB kit. Staining was defined as positive for VEGF and p53, when more than 10% and 5% of the tumor cells were stained out of 500 cells counted, respectively. RESULTS: FIGO stage (p=0.05) and tumor size (p=0.04) were significant prognostic factors for survival. p53 expression was present in 17 (77%) cases. There was no significant relationship between p53 staining and the clinicopathologic factors, such as FIGO stage (p=0.98), tumor size (p=0.43), lymph node status (p=0.82), parametrial invasion (p=0.96), and age (p=0.18). The five year survival rates according to the p53 expression status were 80% for the p53 negative group and 66% for the p53 positive group (p=0.58). Positive VEGF expression was observed in 11 (47%) of the total of 23 patients. Statistical evaluation of VEGF expression according to stage (p=0.36), tumor size(p=0.11), lymph node status (p=0.82), parametrial invasion (p=0.49), and age (p=0.55) revealed no significant difference in any of these parameters. The five year survival rates according to the VEGF expression status were 89% for the VEGF negative group and 41% for the VEGF positive group (p=0.07). CONCLUSION: We suggest that VEGF expression may have an effect on the prognosis of cervix cancer patients treated with radiation therapy, and further evaluation with a large sample size is warranted. PMID- 26680972 TI - Relationship between PTEN and Vascular Endothelial Growth Factor Expression in Non-Small Cell Lung Cancer. AB - PURPOSE: This study was performed to determine the relationship between PTEN and vascular endothelial growth factor (VEGF) expression and to assess their roles in the tumor-induced angiogenesis and tumor progression in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues, from 96 patients diagnosed with NSCLC, were evaluated for VEGF and PTEN expression using immunohistochemical methods. The results of the expression pattern of VEGF alone, or in combination with PTEN expression, were compared with clinicopathological parameters. RESULTS: VEGF expression was seen in 54 (56.3%) of the 96 NSCLCs evaluated, and was significantly correlated with histological type, and seen more frequently in adenocarcinomas compared to the other histological types (p<0.05). There were no significant associations between VEGF expression and tumor size, lymph node metastasis and stage. The microvessel density (MVD) determined by CD34 staining were significantly higher in tumors with VEGF expression (62.9+/-21.8) than those without (55.1+/-15.1). Loss of PTEN expression was seen in 33 (34.4%) of the 96 NSCLCs evaluated. VEGF expression was more frequently detected in the tumors with loss of PTEN expression (69.7%) than in those with PTEN expression (49.2%). When the combined VEGF/ PTEN phenotypes were divide into two groups; group I (VEGF-/PTEN+) and group II (VEGF-/ PTEN-, VEGF+/PTEN+, VEGF+/PTEN-), a significant correlation was also seen between the groups and the histologic types. There was a trend for the tumors in group II to show more frequent lymph node metastasis (50.0%) than those in group I (31.5%), although there was no statistical significance. The MVDs were significantly higher in group II (63.1+/-20.7) than in group I (53.4+/-17.2). CONCLUSION: These findings demonstrate an inverse correlation between the expressions of PTEN and VEGF. It is possible that PTEN may repress VEGF expression, and modulate VEGF mediated angiogenesis, which suggests further analysis of the complex phenomenon of neo-angiogenesis in NSCLC is essential. PMID- 26680973 TI - cDNA Microarray Analysis of Gene Expression Profiles Associated with Cervical Cancer. AB - PURPOSE: The molecular pathology of cervical cancers associated with human papillomavirus infection is presently unclear. In an effort to clarify this issue, the gene expression profiles and pathogenic cellular processes of cervical cancer lesions were investigated. MATERIALS AND METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The tissue samples of 11 patients (invasive cancer stage Ib- IIIa) were investigated by a cDNA microarray of 4, 700 genes, hierarchical clustering and the Gene Ontology (GO). Total RNA from cervical cancer and non-lesional tissues were labeled with Cy5 and Cy3. The HaCaT human epithelial keratinocyte cell line was used as a negative control cell. The stages of invasive cancer were Ib to IIIb. All specimens were obtained by punch-biopsies and frozen in liquid nitrogen until required. RESULTS: 74 genes, showing more than a 2 fold difference in their expressions, were identified in at least 8 of the 11 patients. Of these genes, 33 were up-regulated and 41 were down-regulated. The gene expression profiles were classified into 345 mutually dependent function sets, resulting in 611 cellular processes according to their GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis and nucleic acid metabolism. The genes related to nucleic acid binding and structural molecule activity were also significantly down-regulated. In contrast, significant up regulation was shown in the skeletal development, immune response and extracellular activity. CONCLUSION: These data are suggestive of potentially significant pathogenetic cellular processes, and showed that the down-regulated functional profiling has an important impact on the discovery of pathogenic pathways in cervical carcinogenesis. GO analysis can also overcome the complexity of the expression profiles of the cDNA microarray via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at the cellular process levels. PMID- 26680975 TI - Arsenic Trioxide, an Old Drug? or a New Drug? PMID- 26680974 TI - Use of GCDFP-15 (BRST-2) as a Specific Immunocytochemical Marker for Diagnosis of Gastric Metastasis of Breast Carcinoma. AB - Metastasis of breast cancer to the stomach is relatively uncommon and typically occurs in patients with disseminated diseases. This may cause difficulty in differentiating it from primary gastric carcinoma. The correct diagnosis of the primary source is important, since the treatment and prognosis of metastatic breast cancer is quite different from those of metastatic gastric cancer. Immunohistochemical staining with GCDFP-15 (gross cystic disease fluid protein 15) can be used to differentiate primary gastric carcinoma and gastric metastasis from breast cancer. We report two cases of gastric metastasis of breast cancer by describing their clinical course, illustrating the histologic findings, and showing the results of immunohistochemical staining with GCDFP-15. PMID- 26680976 TI - New Functions for Telomerase. AB - Telomeres are nucleoprotein structures that compose the ends of eukaryotic chromosomes and that regulate chromosome integrity and cell proliferative lifespan. Stabilization of telomere length correlates with cell immortalization, and constitutive activation of telomerase is observed in most human cancers, suggesting that telomere maintenance plays an important role in malignant transformation and possibly aging. However, several lines of evidence indicate that alterations in telomere biology both suppress and facilitate malignant transformation. Moreover, recent observations indicate that telomerase expression plays important regulatory functions beyond the maintenance of telomere length in both normal and malignant cells. Understanding these additional functions of telomerase promise to provide further insight into both normal and malignant cell physiology. PMID- 26680977 TI - Effect of Arsenic Trioxide in TRAIL (Tumor Necrosis Factor-related Apoptosis Inducing Ligand)-Mediated Apoptosis in Multiple Myeloma Cell Lines. AB - PURPOSE: The potential therapeutic application of the tumor necrosis factor related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS: Using TRAIL-sensitive (RPMI- 8226) and TRAIL resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS: Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION: The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells. PMID- 26680978 TI - Telomerase Activity in Gastric Adenocarcinomas: Frozen Tissues Versus Methacarn fixed Paraffin-embedded Tissues. AB - PURPOSE: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosome ends to compensate for sequence loss during DNA replication. It has been detected in 85~90% of all primary human cancers, implicating that its apparent reactivation in tumors may play a role in the tumorigenic process. The purpose of this study was to evaluate telomerase activity in stomach cancer, and to determine whether methacarn-fixed paraffin embedded tissues can replace frozen tissue sections for the telomerase (TRAP) assay. MATERIALS AND METHODS: Frozen and corresponding methacarn-fixed paraffin embedded tissue samples were obtained from 51 patients with gastric adenocarcinoma and analyzed for telomerase activity by using a TRAPeze ELISA kit. RESULTS: Telomerase activity was detected in 37 (73%) frozen samples, and in 13 (25%) methacarn-fixed paraffin blocks. Telomerase activity was well correlated with depth of invasion (p=.037) and tumor differentiation (p=.022). CONCLUSION: These data suggest that reactivated telomerase may play a significant role in the tumorigenesis of gastric cancer and may reflect the malignant potential of the tumor. It is noteworthy that methacarn- fixed tissue cannot as yet substitute for the frozen tissue in the TRAP assay. PMID- 26680979 TI - Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Lung Cancer Susceptibility of Korean Population. AB - PURPOSE: Although 80~90% of patients with lung cancer are smokers, only 11% of smokers develop lung cancer. Genetic susceptibility according to the polymorphism of the epoxide hydrolase (mEPHX) gene and homozygous deletion of GSTM1 (M1 subunit of Glutathione S transferase) was studied in this case control study. MATERIALS AND METHODS: Genomic DNA from 76 subjects with lung cancer (40 squamous cell carcinoma, 13 adenocarcinoma, 10 subtype undetermined non-small cell lung cancer, and 13 small cell lung carcinoma) and 62 age- matched controls were extracted from peripheral white blood cells. PCR and RFLP (restriction fragments length polymorphism) with restriction enzyme (RsaI) and automatic sequencing were used for mEPHX genotyping (T-->C, Tyr113His) in exon 3 and (A-->G, His139Arg) in exon 4. Looking for homozygous deletions of GSTM1, multiplex PCR with primers for the GSTM1 gene and coagulation factor V gene (as positive control) were performed. RESULTS: The age distribution between the cancer and control groups were similar (63.6 7.2 vs. 61.1 7.9 years). The lung cancer group, however, had more smokers (73.3%, 44/60) than the control group (21/54, 38.9%, p<0.001). The rate of homozygous deletion of the GSTM1 gene was significantly higher in the lung cancer group (65.8%, 50/76) than in the control group (46.8%, 29/62, p<0.05), causing the relative risk of GSTM1 deletion for lung cancer as 2.19 (95% CI: 1.10~4.35, p=0.02). Among 118 subjects whose mEPHX gene polymorphisms were studied, 62 (52.5%) subjects showed genotypes with slow enzyme activity while 45 (38.1%) showed normal enzyme activity and 11 (9.3%) showed fast enzyme activity. There was no significant difference in the distribution of mEPHX gene polymorphisms between the two groups. CONCLUSION: The homozygous deletion of the GSTM1 gene was associated with high lung cancer susceptibility, whereas the mEPHX genotype showed no significant connection with risk of lung cancer in a sample Korean population. PMID- 26680980 TI - Proteomic Profiling of Human Small Cell Lung Cancer Cell Line NCI-H211. AB - PURPOSE: Small cell lung cancer is one of the major causes of death from cancer worldwide. To explore the expressions of global protein in small cell lung cancer cells, a proteomic approach, to identify the proteins, was used and the establishment of a protein reference map attempted. MATERIALS AND METHODS: Two dimensional gel electrophoresis (2-DE), with subsequent analysis by mass spectrometry (MS), was applied to the study of protein identification from a small cell lung cancer cell line, NCI- H211. The cells were lysed, and the extracts subjected to isoelectric focusing, with immobilized pH gradients, followed by second dimension SDS-PAGE. The polypeptides were identified by peptide mass fingerprinting, with MALDI-TOF MS, after in-gel protein digestion. RESULTS: From silver staining of the gel, around two thousands protein spots were separated by the 2-DE. Of these protein spots visualized in the gel, one hundred and ten were identified by peptide mass fingerprinting. Different proteins, such as enzymes, cytoskeletal proteins and proteins common to eukaryotic cells, were identified. CONCLUSION: The protein expressions of the small cell lung cancer cells were analyzed to establish a protein reference map. The reference map presented here may serve as a working tool for the further study of small cell lung cancer. PMID- 26680981 TI - The Relation between Histopathologic Findings on Surgical Specimen and Outcomes in Patients with N2 Positive Stage IIIA Non-Small Cell Lung Cancer Receiving Preoperative Concurrent Radiochemotherapy and Surgery. AB - PURPOSE: To evaluate the prognostic implication of histopathologic findings on the surgical specimens of N2 positive stage IIIA non-small cell lung cancer (NSCLC) patients who were treated with preoperative concurrent radiochemotherapy (CRCT) and surgery. MATERIALS AND METHODS: From May 1997 to April 2000, 48 patients with N2 positive stage IIIA NSCLC were treated with preoperative CRCT and surgery. Retrospective analyses were performed on 33 patients who underwent surgical resection. The thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks with a 1.8 Gy daily fraction using 10 MV X-rays. Chemotherapy consisted of two cycles of intravenous cisplatin (100 mg/m2, on days 1 and 29) and oral etoposide (50 mg/m2/day, on days 1~14 and 29~42), concurrently delivered with TRT. Surgery was performed around 4 weeks of the completion of CRCT. The median follow up was 18 months. The histopathologic findings, including the proportions of viable tumor cells, fibrosis, and necrosis, as well as the tumor and nodal statuses on the surgical specimens following the preoperative CRCT, were analyzed. RESULTS: The 3-year overall survival, disease-free survival, and local control rates were 46.1%, 49.5%, and 85.5%, respectively. Post-surgical stages decreased in 18 patients (54.5%), including 3 pathologic complete responses, were unchanged in 13 (39.4%), and increased in two (6.1%). On univariate analyses, the low proportion of the viable tumor cells was the only factor favorably affecting the overall survival rate (p=0.0386), and the histologic type of squamous cell carcinoma was a favorable factor affecting disease free survival rate (p=0.0452). On multivariate analyses, however, no factor affected the overall survival, disease free survival, or local control rates. CONCLUSION: The histopathologic findings of the proportion of viable tumor cells, fibrosis, and necrosis on the surgical specimens following preoperative CRCT had few prognostic implications on uni-and multi-variate analyses. Furthermore, the primary tumor and nodal responses to preoperative CRCT did not influence the outcomes. Longer-term follow up with a larger number of patients, however, is awaited. PMID- 26680982 TI - The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer. AB - PURPOSE: The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events. CONCLUSION: The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens. PMID- 26680983 TI - Combined Cytoreductive Surgery and Early Postoperative Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Gastric Cancer. AB - PURPOSE: Peritoneal seeding is the most common type of metastasis or recurrence and one of the poor prognostic factors in gastric cancer. Moreover, there are as yet no effective treatment modalities available. Recently some research groups suggested the benefit of combined cytoreductive surgery and intraperitoneal chemotherapy, but the related experiments remain in the trial stage. Therefore, we assessed the safety and evaluated the efficacy of combined cytoreductive surgery and early postoperative intraperitoneal chemotherapy (EPIC) in gastric cancer patients with peritoneal carcinomatosis of gastric cancer. MATERIALS AND METHODS: From Nov. 1997 to May. 2002, eighteen cases of combined cytoreduction and EPIC were performed in the Korea Cancer Center Hospital due to gastric cancer with peritoneal carcinomatosis. The control group consisted of 33 patients who had no resection without EPIC during the same periods. After combined cytoreductive surgery and EPIC, all patients received systemic chemotheraphy with the exception of 2 patients who could not tolerate the treatment. We retrospectively investigated the clinicopathologic features and analyzed the factors affecting the prognosis. Median follow-up period was 11.9 months (range 0.5~61 months). Statistical analysis was performed by SPSS 11.0 for Windows. A P value less than 0.05 was considered as statistically significant. RESULTS: There was one case of the treatment-related mortality (5.5%) and seven cases of treatment-related complications (38%) in the combined cytoreductive surgery and intraperitoneal chemotherapy group. One-, 3- and 5-year survival rates of cytoreductive surgery plus EPIC were 57.6%, 25.9% and 13.0%, respectively, and those of the control group were 18.2%, 3% and 0%, respectively. Survival of the combined cytoreductive surgery plus EPIC group was better than that of the control group (p=0.0026). In multivariate analysis of prognostic factors affecting the survival, combined cytoreductive surgery plus EPIC (p=0.02) and systemic chemotherapy (p=0.019) were independent prognostic factors. CONCLUSION: Although a small number of cases were included in this study, combined cytoreductive surgery plus EPIC showed survival benefit and retained a comparable complication rate compared with the control group. PMID- 26680984 TI - Correlation between p53 and Rb Protein Expression and Clinicopathologic Features in Hepatocellular Carcinoma. AB - PURPOSE: Hepatocellular carcinomas (HCC) are one of the most common cancers in Korea. The mechanism of HCC development is still unclear, and the aberration of the tumor suppressor genes in HCC remains to be clarified. MATERIALS AND METHODS: To study the expressions of p53 and Rb protein, and their correlation with the clinicopathological parameters in HCC, 68 patients, with surgically resected hepatocellular carcinomas, were analyzed by an immunohistochemical method. The expressions of p53 and Rb protein were classified into three categorizes, depending on the percentage of stained cells. RESULTS: The expression of the p53 protein was 51.5% (35/68), and was significantly correlated with differentiation (p<0.05). The altered Rb protein expression was 72.2% (49/68). The expressions of p53 and altered Rb protein had no significant correlation with the tumor size, gender, WHO histological pattern, cirrhosis or vascular invasion (p>0.05). There was a positive correlation between p53 and Rb protein overexpression (p<0.05). The expressions of p53 and Rb protein had correlation with the Ki-67 labeling index (p<0.05). CONCLUSION: These findings suggest the aberrant expressions of p53 and Rb protein may play a role in the progression and carcinogenesis of HCC. PMID- 26680985 TI - Growth Suppression and Induction of Chemosensitivity in Human Gallbladder Epithelial Carcinoma Cells (GBCE) by Adenovirus-Mediated Transfer of the Wild type p53 Gene. AB - PURPOSE: Mutations in the p53 gene are reported in 50~90% of gallbladder and bile duct cancer, and have been implicated in chemoresistance. We undertook this study to determine whether the introduction of the wild type p53 gene into GBCE (human gallbladder cancer cell line with a heterozygous p53 mutation) by an adenoviral vector could increase the sensitivity of the cell to 5-FU, a commonly used drug in the treatment of gallbladder cancer. MATERIALS AND METHODS: GBCE cells were transfected with either Ad/p53 or Ad/E1 in the presence of 5-FU. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with GBCE cells. When tumors formed, intratumoral injection of Ad/p53 was performed. Reduction of tumor size was compared in two weeks of Ad/p53 gene transfection. RESULTS: Ad/53 transfection induced a dose-dependent inhibition of tumor growth. Tumor colony formation was more inhibited with p53 gene transfection than with mock transfection in the presence of 5-FU. The reduction in tumor size was more pronounced with p53 transfection than with mock infection. CONCLUSION: These treatment modalities could be utilized in the treatment of p53 mutant human gallbladder cancers. PMID- 26680986 TI - The Combined Effects of Amifostine and Interleukin 1 Beta (IL-1beta) on Radiation induced Gastrointestinal and Hematopoietic Injury. AB - PURPOSE: The pattern of radioprotection by the combined use of low dose amifostine plus IL-1beta was investigated in mice exposed to an acute whole-body radiation dose of 10 Gy. MATERIALS AND METHODS: Male ICR mice were divided into the control group, the irradiation-only group, the high dose amifostine (400 mg/kg i.p. 30 min before irradiation) group, and the low dose amifostine (200 mg/kg i.p. 30 min before irradiation) plus IL-1beta (5 microgram/kg i.p. 20 h before irradiation) group. The radioprotective effects were evaluated using TUNEL assay and microcolony survival assay at jejunal crypt, bone marrow cell count and CBC in peripheral blood, and survival analysis up to 30 days following irradiation. RESULTS: The apoptotic index (p=0.987), surviving crypt number (p=0.484), and the number of WBCs (p=0.226), RBCs (p=0.544), and platelets (p=0.157) were not significantly different between the high dose amifostine group and the low dose amifostine plus IL-1beta group, although the bone marrow cell count was higher in the combination group. The irradiation-only group was dead within 15 days. However, the survival rate at 30 days in the high dose amifostine and the low dose amifostine plus IL-1beta pretreatments were 61% and 66%, respectively. Moreover, the differences between the two groups were insignificant for both 10 days (p=0.9461) and 30 days (p=0.8030). CONCLUSION: These results indicate that the low dose amifostine plus IL-1beta may be applied as a non-toxic radioprotector, while the high dose amifostine, known as the strongest radioprotector, however, had toxic side effects. PMID- 26680987 TI - cDNA Microarray Experiment: Design Issues in Early Stage and the Need of Normalization. AB - PURPOSE: The cDNA microarray has become a useful tool for observing the expression of thousands of genes simultaneously. However, obtaining good quality microarray data is not easy due to the inherent noise at various stages of the experiment. Therefore, it is essential to understand the source of the variation in the microarray experiment and its size as an initial step of the data analyses. MATERIALS AND METHODS: The total RNA extracted from HT-1080 fibrosarcoma and normal rat tissues were hybridized to the cDNA microarrays with 0.5 K human and 5 K rat genes, respectively. A homotypic reaction and dye swap experiments were used to identify the sources of the variation. RESULTS: The relative fluorescent intensities of the microarray, if unnormalized, have a large variation, particularly in the lower intensity region. The distribution of the log intensity ratios also exhibit some departure from a band around zero, which is the distribution pattern expected when the majority of genes in the microarray are not regulated. Normalization of the log ratios is usually required as a means of preprocessing the data. We claim that a within-print tip group, an intensity dependent normalization through a loess fit adjustment will be useful for this purpose, particularly in the initial stages of the microarray experiment. CONCLUSION: For proper data analysis, an understanding the source of the variation and preprocessing of data with a suitable normalization method will be important. It is important to have an interactive cooperation between a researcher and a statistician from the early stages of the study design and to the final stages of data analysis. PMID- 26680988 TI - Speculoscopy as Pap Smear Adjunct. AB - PURPOSE: Speculoscopy, or magnified chemiluminescent examination (MCE), is a new visual method for the detection of cervical neoplasia. It utilizes low magnification and a special "blue-white" chemiluminescent light. The purpose of this study was to evaluate the screening effectiveness of speculoscopy combined with the conventional Papanicolaou smear, as compared with the latter alone, through a clinical trial in Korea. MATERIALS AND METHODS: This prospective, randomized, university hospital-based clinical study was performed in the outpatient clinic of the Department of Obstetrics and Gynecology at Dankook University Medical Center from December 1, 2001 to June 30, 2002. Of the 113 patients aged 19~74 years who had undergone both conventional Papanicolaou cervical cytologic test and speculoscopy, 38 cases underwent histologic diagnoses by colposcopy- directed biopsy. RESULTS: Of the 113 patients, there were 87 (77.0%) spe-culoscopy diagnoses of negative, 9 (8.0%) of suspicious, and 17 (15.0%) of positive. Of the 38 histologic diagnoses, there were 19 (50.0%) diagnoses of negative, 7 (18.4%) of LSIL, 1 (2.6%) of HSIL, 10 (26.3%) of SCC, and 1 (2.6%) of ACC. Pap smear showed sensitivity of 77.8% and specificity of 81.3%, whereas speculoscopy showed 94.1% and 100.0%, respectively, and Pap smear combined with speculoscopy showed 100.0% and 81.3%, respectively. CONCLUSION: Speculoscopy showed a higher sensitivity rate than Pap smear as a screening test, although the sample size was small. Speculoscopy combined with Pap smear is thought to be a very effective method for detecting cervical neoplasia. PMID- 26680989 TI - Photogem Induces Necrosis in Various Uterine Cervical Cancer Cell Lines by PDT. AB - PURPOSE: In order to elucidate the antitumor effect of photodynamic therapy (PDT), using a derivative of the photosensitizing agent hematoporphyrin (Photogem) and a diode laser, the cell death of uterine cancer cell lines (CaSki, HT3, HeLa, and SKOV-3), and mice transplanted with TC-1 lung cancer cells, were evaluated. MATERIALS AND METHODS: The morphological changes, MTT assay, flow cytometry, cytotoxicity and tumor growth inhibition study were evaluated at various time intervals after the PDT. RESULTS: The results showed that the survival rates of each cell line decreased with time and dose response after performing the PDT. Also, the PDT-induced damage of cancer cells was almost entirely confined to necrosis of the tumor cells in the early time courses. The irradiation of CaSki cells in the presence of Photogem induced plasma membrane disruption and cell shrinkage, indicating the plasma membrane as the main target for Photogem. In the in vivo experiment, significantly longer survival and a significantly smaller tumor size were seen over the time courses of the Photogem with irradiation compared to the untreated control groups; resorption of the tumor was also observed after the PDT treatment. CONCLUSION: Collectively, our results indicated that Photogem possesses anti-tumor effects, and necrosis-like death, with plasma membrane damage, was postulated to be the principal mechanism of the antitumor effect of the PDT using Photogem. PMID- 26680990 TI - Evidence supporting a critical contribution of intrinsically disordered regions to the biochemical behavior of full-length human HP1gamma. AB - HP1gamma, a non-histone chromatin protein, has elicited significant attention because of its role in gene silencing, elongation, splicing, DNA repair, cell growth, differentiation, and many other cancer-associated processes, including therapy resistance. These characteristics make it an ideal target for developing small drugs for both mechanistic experimentation and potential therapies. While high-resolution structures of the two globular regions of HP1gamma, the chromo- and chromoshadow domains, have been solved, little is currently known about the conformational behavior of the full-length protein. Consequently, in the current study, we use threading, homology-based molecular modeling, molecular mechanics calculations, and molecular dynamics simulations to develop models that allow us to infer properties of full-length HP1gamma at an atomic resolution level. HP1gamma appears as an elongated molecule in which three Intrinsically Disordered Regions (IDRs, 1, 2, and 3) endow this protein with dynamic flexibility, intermolecular recognition properties, and the ability to integrate signals from various intracellular pathways. Our modeling also suggests that the dynamic flexibility imparted to HP1gamma by the three IDRs is important for linking nucleosomes with PXVXL motif-containing proteins, in a chromatin environment. The importance of the IDRs in intermolecular recognition is illustrated by the building and study of both IDR2 HP1gamma-importin-alpha and IDR1 and IDR2 HP1gamma-DNA complexes. The ability of the three IDRs for integrating cell signals is demonstrated by combined linear motif analyses and molecular dynamics simulations showing that posttranslational modifications can generate a histone mimetic sequence within the IDR2 of HP1gamma, which when bound by the chromodomain can lead to an autoinhibited state. Combined, these data underscore the importance of IDRs 1, 2, and 3 in defining the structural and dynamic properties of HP1gamma, discoveries that have both mechanistic and potentially biomedical relevance. PMID- 26680991 TI - Active site binding modes of inhibitors of Staphylococcus aureus mevalonate diphosphate decarboxylase from docking and molecular dynamics simulations. AB - Bacterial mevalonate diphosphate decarboxylase (MDD) is an attractive therapeutic target for antibacterial drug development. In this work, we discuss a combined docking and molecular dynamics strategy toward inhibitor binding to bacterial MDD. The docking parameters utilized in this study were first validated with observations for the inhibitors 6-fluoromevalonate diphosphate (FMVAPP) and diphosphoglycolylproline (DPGP) using existing structures for the Staphylococcus epidermidis enzyme. The validated docking protocol was then used to predict structures of the inhibitors bound to Staphylococcus aureus MDD using the unliganded crystal structure of Staphylococcus aureus MDD. We also investigated a possible interactions improvement by combining this docking method with molecular dynamics simulations. Thus, the predicted docking structures were analyzed in a molecular dynamics trajectory to generate dynamic models and reinforce the predicted binding modes. FMVAPP is predicted to make more extensive contacts with S. aureus MDD, forming stable hydrogen bonds with Arg144, Arg193, Lys21, Ser107, and Tyr18, as well as making stable hydrophobic interactions with Tyr18, Trp19, and Met196. The differences in predicted binding are supported by experimentally determined Ki values of 0.23 +/- 0.02 and 34 +/- 8 MUM, for FMVAPP and DPGP, respectively. The structural information coupled with the kinetic characterization obtained from this study should be useful in defining the requirements for inhibition as well as in guiding the selection of active compounds for inhibitor optimization. PMID- 26680992 TI - Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting. AB - Human Dopamine Receptor D4 (DRD4) orchestrates several neurological functions and represents a target for many psychological disorders. Here, we examined two rare variants in DRD4; V194G and R237L, which elicit functional alterations leading to disruption of ligand binding and G protein coupling, respectively. Using atomistic molecular dynamics (MD) simulations, we provide in-depth analysis to reveal structural signatures of wild and mutant complexes with their bound agonist and antagonist ligands. We constructed intra-protein network graphs to discriminate the global conformational changes induced by mutations. The simulations also allowed us to elucidate the local side-chain dynamical variations in ligand-bound mutant receptors. The data suggest that the mutation in transmembrane V (V194G) drastically disrupts the organization of ligand binding site and causes disorder in the native helical arrangement. Interestingly, the R237L mutation leads to significant rewiring of side-chain contacts in the intracellular loop 3 (site of mutation) and also affects the distant transmembrane topology. Additionally, these mutations lead to compact ICL3 region compared to the wild type, indicating that the receptor would be inaccessible for G protein coupling. Our findings thus reveal unreported structural determinants of the mutated DRD4 receptor and provide a robust framework for design of effective novel drugs. PMID- 26680993 TI - Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry. AB - BACKGROUND: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. METHODS: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. RESULTS: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. CONCLUSIONS: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population. PMID- 26680995 TI - Salivaomics for oral diseases biomarkers detection. AB - The variation of saliva composition in different physiological and pathological states is well demonstrated. Several saliva constituents (enzymes, hormones, antibodies, cytokines etc.) are up- or down-regulated in respect to benign, premalignant and malignant conditions in the oral cavity, and several patterns of deregulation are associated with specific disorders. Omics technologies have contributed significantly in the identification of alterations in gene expression, transcription, protein coding and small molecules concentration, in biologic systems. In this aspect, salivaomics integrate these technologies in saliva analysis and represent a novel and holistic approach in oral disease management including diagnosis, prognosis and monitoring. This review summarizes the current research in the discovery of biomarkers and molecular signatures with diagnostic or prognostic utility for oral diseases in saliva. The review also focuses on the emerging issues of the salivaomics technology and saliva diagnostics and the translational potential. PMID- 26680996 TI - Data protection: balancing personal privacy and public health. PMID- 26680997 TI - Proper Evaluation of Factors Affecting Oxidative Status. PMID- 26680994 TI - Worldwide patterns of genomic variation and admixture in gray wolves. AB - The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World. However, no single wolf population is more closely related to dogs, supporting the hypothesis that dogs were derived from an extinct wolf population. All extant wolves have a surprisingly recent common ancestry and experienced a dramatic population decline beginning at least ~30 thousand years ago (kya). We suggest this crisis was related to the colonization of Eurasia by modern human hunter-gatherers, who competed with wolves for limited prey but also domesticated them, leading to a compensatory population expansion of dogs. We found extensive admixture between dogs and wolves, with up to 25% of Eurasian wolf genomes showing signs of dog ancestry. Dogs have influenced the recent history of wolves through admixture and vice versa, potentially enhancing adaptation. Simple scenarios of dog domestication are confounded by admixture, and studies that do not take admixture into account with specific demographic models are problematic. PMID- 26680998 TI - Enantiopure anion templated synthesis of a zeolitic metal-organic framework. AB - Utilizing (R)-H3CIA as a chiral template, an unprecedented homochiral metal organic framework (MOF) with zeotype GIS topology is obtained from achiral 1.4 DIB ligands and Zn(II) ions, which opens up a feasible approach to create zeolitic MOFs with homochirality. PMID- 26680999 TI - Psychological disorders and oral lichen planus: matched case-control study and literature review. AB - OBJECTIVE: Oral lichen planus (OLP) may be linked to psychological disorders. This study investigated psychological factors associated with OLP. METHODS: A case-control study with incident OLP case patients and age-gender-socio-economic status-matched controls, recruited from among relatives, accompanying persons, and departmental staff, investigated psychological traits using the Psychological General Well-Being Index-Short form. Common factor analysis was used to generate a set of psychological dimensions. The association between these dimensions and OLP adjusted for confounders (education, number of lifetime sexual partners, drinking-smoking) and interactions was assessed through conditional logistic regression and odds ratios (OR) were estimated. RESULTS: A total of 67 case control pairs were recruited. Psychological dimensions generated were: dimension 1 (anxiety, low vitality), dimension-2 (negative well-being, low vitality), dimension-3 (depressed mood, low self-control). The ORs for OLP were, dimension 1, 1.0 (95% confidence interval -95CI, 0.3-2.6); dimension-2, 0.5 (95CI, 0.2 1.2); dimension-3, 4.8 (95CI, 1.8-12.9). Dimension-3 was highly associated with mild, but not associated with severe, OLP. Literature searching provided 21 studies, with anxiety and depression principally associated with OLP. CONCLUSIONS: Depressed mood and low self-control were highly associated with OLP, particularly the reticular-papular forms. These traits could have a causative role in OLP development-progression, but further investigations are necessary. PMID- 26681000 TI - Detection of serum antinuclear antibodies in lymphoma patients. AB - We investigated the presence of serum antinuclear antibodies (ANAs) and autoantibodies and their relationship with serum prognostic indicators in lymphoma patients. The study population comprised 127 patients diagnosed with lymphoma and 138 healthy control subjects. The blood samples of the participants were assayed for ANAs by immunofluorescence, and autoantibodies were detected by western blotting. Serum ANAs were detected in 31.5 (40/127) and 6.5% (9/138) of lymphoma patients and control subjects, respectively. There was a statistically significant difference between the lymphoma and the control groups (P < 0.05). The level of lactate dehydrogenase in the ANA-positive subjects was significantly lower than in the ANA-negative subjects (P < 0.05). Low ANA titers (1:100) were commonly found in the ANA-positive subjects and the control subjects, and the fluorescence models were diverse. Autoantibodies were found in 35% (14/40) of the ANA-positive patients by western blotting. Detection of ANAs in lymphoma patients helps in determining the diagnosis and prognosis of lymphoma, but has no independent diagnostic value; there are still various autoantibodies of unknown significance that require further study. PMID- 26681001 TI - Effect of human umbilical cord mesenchymal stem cells on endometriotic cell proliferation and apoptosis. AB - The objective of this study was to observe the effects of human umbilical cord mesenchymal stem cells (UCMSCs) on the proliferation and apoptosis of endometriotic cells. Endometriotic cells and UCMSCs were primarily cultured in vitro. In the experimental group, a UCMSC and endometriotic cell non-contact co culture system was established. The control group consisted of 1 x 10(5) endometriotic cells cultured alone. The proliferation and apoptosis of endometriotic cells were respectively detected using the MTT method and flow cytometry. The mRNA expression level of the tensin homologue gene (PTEN) in endometriotic cells was detected by reverse transcription-polymerase chain reaction amplification. Compared with the control group, the proliferation of endometriotic cells in the experimental group was clearly inhibited (P < 0.05) and time-dependent (P < 0.05). In addition, the number of apoptotic cells were significantly increased (P < 0.05), and the amount of cells, which entered S phase from G1 phase, decreased significantly. Furthermore, the mRNA expression level of the PTEN gene in the experimental group was significantly higher than in the control group (P < 0.05). These results suggest that UCMSCs might inhibit the proliferation of human endometriotic cells in vitro and promote their apoptosis by upregulating the expression of PTEN. PMID- 26681002 TI - Identification of microRNAs as diagnostic biomarkers in screening of head and neck cancer: a meta-analysis. AB - Head and neck cancer (HNC) is one of the most prevalent cancers; it is often diagnosed at its advanced stage and has a low 5-year survival rate. Evidence suggests that noninvasive biomarker microRNAs (miRNAs) are valuable for early diagnosis of HNC. This meta-analysis assessed the diagnostic value of miRNAs in HNC detection. A systematic literature search for relevant studies up to August 4, 2014 was conducted in databases and other sources. Statistical analysis was conducted using STATA 12.0. Pooled sensitivity, specificity, and other parameters, together with a summary receiver operating characteristic curve were used to assess the overall performance of miRNA assays. Subgroup analyses and meta-regression were used to analyze heterogeneity, and a Deeks' funnel plot asymmetry test assessed publication bias. Twenty-four articles with 1856 HNC patients and 1375 controls were included. The pooled results were as follows: sensitivity, 0.80 (95%CI = 0.77-0.83); specificity, 0.80 (95%CI = 0.76-0.85); positive likelihood ratio, 4.1 (95%CI = 3.2-5.2); negative likelihood ratio, 0.25 (95%CI = 0.21-0.30); diagnostic odds ratio (DOR), 16 (95%CI = 11-24); and area under curve (AUC), 0.87 (95%CI = 0.84-0.89). We conducted subgroup analyses based on ethnicity, cancer type, miRNA profiling, and specimen types, and found that miRNA assays yielded the highest accuracy in esophageal cancer. Notably, the DOR was 99 and the AUC was 0.96 for the multiple miRNA test, indicating strong discrimination of cancer patients from healthy people. The meta-analysis indicates that noninvasive miRNAs are a promising diagnostic tool with moderate accuracy for HNC diagnosis. PMID- 26681003 TI - Cloning and sequence analysis of the LOC339524 gene in Sprague-Dawley rats. AB - We cloned the LOC339524 gene in Sprague-Dawley (SD) rats and analyzed the structure and function of the protein encoded by it. Based on the known human LOC339524 gene sequences, the full-length coding sequence of the LOC339524 gene in SD rats was cloned and amplified by the polymerase chain reaction using the complementary DNA of SD rats as a template. Bioinformatics analysis showed that the length of the cloned LOC339524 gene (GenBank accession No. KM224520) was 831 bp and it encoded a deduced protein of 276 amino acids. Sequence analysis revealed that the coded protein was identical to that produced in humans and its functional domain was located in the 138-236 amino acid fragments, a proline-rich region. Our results suggest that the encoded protein may be a significant regulator of the inflammatory response and may provide sufficient information to justify an in-depth investigation of the role of the LOC339524 gene. PMID- 26681004 TI - Evaluation of the genotoxic activity of dicamba and atrazine herbicides in several Mexican and South American varieties of sweetcorn (Zea mays L.). AB - Corn is a major crop and various herbicides are used to maximize its production, which include a dicamba-atrazine mixture. This has great advantages, but can also induce DNA damage. Genotoxic activity was assessed by comet assay following application of two concentrations of dicamba-atrazine: 1000-2000 and 2000-4000 ppm. Apical meristem leaf nuclei from 119 varieties of sweetcorn plants from Mexico and South America, and from five commercial sweetcorn hybrids were used. Each accession comprised two individuals per concentration and two controls. Significant genotoxic activity (P < 0.001) was observed following treatment with 1000-2000 and 2000-4000 ppm compared to the negative control. There was no difference in the genotoxic activity induced by both 1000-2000 and 2000-4000 ppm concentrations in plants from Mexico and South America (P > 0.05) except (P < 0.05) in the 2000-4000 ppm treated plants from Mexico and the 1000-2000 ppm treated plants from South America. Sweetcorn hybrids showed significant genetic damage (P < 0.01) at all concentrations compared to the negative controls. Thus, the dicamba-atrazine mixture caused genetic damage to corn plants, and it suggested that Mexican sweetcorn is more sensitive to dicamba-atrazine than the maize varieties from South America. Neither hybrid status nor the origin avoids DNA damage caused by Marvel. Thus, maize can be useful as a biomonitor of genetic damage induced by chemicals and to identify possible phenotypes based upon the amount of genetic damage induced by herbicides and selection of resistant genotypes. PMID- 26681005 TI - Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing. AB - CYP2B6 is a highly polymorphic isoenzyme involved in the metabolism of many drugs including cyclophosphamide, bupropion, and efavirenz. A single nucleotide polymorphism (SNP) in CYP2B6 (516G>T) resulted in decreased expression and function associated with the CYP2B6*6 haplotype. Among the clinical implications of this phenotype, decreased activation of cyclophosphamide and increased plasma levels of efavirenz associated with increased central nervous system toxicity have been reported. The frequency of the CYP2B6 (516G>T) SNP has been studied in several different populations, but there is no data regarding distribution among Argentinians. In this study, 102 DNA samples from healthy volunteers were analyzed using a polymerase chain reaction-restriction fragment length polymorphism reaction specific for the CYP2B6 (516G>T) SNP. Our results showed a prevalence of 71.08% for the G allele and 28.92% for the T allele. This was distributed as 52.9% for the GG genotype (reduced dosage required), 36.6% for the GT genotype (normal dosage range), and 10.8% for the TT genotype (high drug toxicity). There was no preferential gender distribution observed. The relatively high prevalence of the TT genotype in our population supports the clinical use of genotyping as an additional tool in personalized medicine. PMID- 26681006 TI - Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility. AB - Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15 4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence. PMID- 26681007 TI - Genetic diversity and the conservation priority of Glycine soja populations from Northern China. AB - Knowledge of the spatial patterns of genetic variation in wild populations has significant implications for in situ conservation and the determination of conservation order. To study the levels of genetic diversity, spatial genetic structures, and genetic distances in Glycine soja, 11 natural populations in northern China were analyzed by estimating genetic coefficients using inter simple sequence repeat (ISSR) fingerprints via mixed sampling strategies. Sixteen ISSR primers generated 98 reproducible polymorphic amplification banding patterns of 172 scored, accounting for 56.98% of the polymorphisms among the populations. The dendrogram based on Nei's genetic distance showed that distinct genetic differentiation occurred in G. soja. The Unweighted Pair-Group Method with Arithmetic Mean cluster analysis indicated two broad groups, and one contained all of the populations except three from Chengde, which formed the smaller second group. The spatial genetic structure evident in the wild soybean populations may be attributed to restricted seed dispersal and the dominant breeding system of this species. The detection of genetic structures in wild soybean populations could be a significant index for the effective conservation of many wild populations, and it could be exploited by soybean breeding programs to increase production. PMID- 26681008 TI - Dietary zinc may attenuate heat-induced testicular oxidative stress in mice via up-regulation of Cu-Zn SOD. AB - Zinc (Zn) is important for male mammalian reproduction. In this study, we sought to clarify the role of Zn in heat-induced testicular damage in mice. Eighteen mice were divided into either control (con), heat (heat) and heat plus Zn (H+Zn) treatment groups, and fed diets containing 60 (con and heat groups) or 300 (H+Zn group) mg/kg Zn sulfate for one month. Mice in the con group were then maintained at 25 degrees C, while mice in heat and H+Zn groups were exposed to 40 degrees C for 2 h daily, for eight days. Mouse testes and serum from each animal were analyzed. Zinc levels in serum and testes were positively correlated to Zn feed concentrations. Mice in the heat group had higher testes index than those in the other two groups (7.22 +/- 0.75, heat; 4.92 +/- 0.20, con; 4.80 +/- 0.30 mg/g, H+Zn; P < 0.05). Testicular antioxidant status showed malondialdehyde levels in heat group mice were increased compared to control mice (2.34 +/- 0.15 versus 1.55 +/- 0.23 nmol/mg protein; P < 0.05), and Cu-Zn superoxide dismutase (SOD) level differed between heat and H+Zn groups (14.04 +/- 0.74 versus 18.27 +/- 1.53 U/mg protein; P < 0.05). Testicular Cu-Zn SOD protein expression levels were significantly lower in the heat than in the control group (0.30 +/- 0.11 versus 1.22 +/- 0.13; P < 0.05). These results suggest that dietary Zn may elevate the activity and protein concentration of Cu-Zn SOD, to attenuate testicular oxidative stress induced by heat exposure. PMID- 26681009 TI - Detection and characterization of carbendazim resistance in Sclerotinia sclerotiorum isolates from oilseed rape in Anhui Province of China. AB - Stem rot caused by Sclerotinia sclerotiorum is a devastating disease of oilseed rape (Brassica napus) in Anhui Province of China. The fungicide carbendazim (methyl benzimidazole-2-yl carbamate; MBC) has been used to control this fungal disease since the 1980s. In the present study, 74 isolates of S. sclerotiorum from 13 regions of Anhui were collected, and the sensitivities of these isolates to MBC were examined to monitor fungicide resistance. We found that 22 of the 74 isolates showed resistance to MBC, indicating that S. sclerotiorum has developed resistance in parts of Anhui Province. PCR assays and DNA sequence analysis showed that isolates with high MBC resistance had a point mutation at position 198 in the beta-tubulin gene that caused a glutamic acid-to-alanine change in the protein. The beta-tubulin gene in low-resistance isolates did not have the mutation. These results indicate that the mutation in beta-tubulin gene may be associated with high MBC resistance in S. sclerotiorum. The present study also found no correlation between MBC resistance and pathogenicity of S. sclerotiorum isolates, suggesting that the pathogenicity of S. sclerotiorum isolates on oilseed rape did not vary with MBC resistance status. PMID- 26681011 TI - Effects of cetuximab combined with afatinib on the expression of KDR and AQP1 in lung cancer. AB - In this study, we examined the effect of cetuximab (epidermal growth factor receptor monoclonal antibody) combined with afatinib (epidermal growth factor receptorand human epidermal growth factor receptor 2 tyrosine kinase irreversible inhibitor) on the apoptosis of A549 cells and on kinase domain receptor (KDR) and aquaporin 1 (AQP1) expression in A549 cells. A549 cells were cultured in RPMI 1640 and then divided into 4 groups: control group, 1-nM cetuximab group, 25-MUM afatinib group, and 1-nM cetuximab + 25-MUM afatinib group. After incubation for 48 h, the cell inhibition rate, cell cycle distribution, and invasive ability of A549 cells before and after treatment were examined using MTT, flow cytometry, and transwell assays, respectively. Gene and protein expression levels of KDR and AQP1 were detected by reverse transcription-polymerase chain reaction and western blot analysis. Cetuximab and afatinib significantly inhibited A549 cell growth. Their combination produced greater growth inhibition (P < 0.01). Cetuximab and afatinib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P < 0.01). Compared with monotherapy, cetuximab in combination with afatinib induced G1 phase arrest and downregulated the gene and protein expression of KDR and AQP1 (P < 0.05). Cetuximab in combination with afatinib synergistically inhibited the growth and migration of cells and downregulated the gene and protein expression of KDR and AQP1, indicating that a combination of cetuximab and afatinib is a potential strategy for lung cancer therapy. PMID- 26681010 TI - Characterization of hemocyanin from the mud crab Scylla paramamosain and its expression analysis in different tissues, at various stages, and under Vibrio parahaemolyticus infection. AB - Hemocyanin is an important respiratory protein in many arthropod and mollusk species. Here, four cDNAs (SpHc1, SpHc2, SpHc3, and SpHc4), encoding distinct hemocyanin subunits from Scylla paramamosain were cloned using EST analyses and the rapid amplification of cDNA ends. The four full-length cDNA fragments (SpHc1 4) were 2281, 2002, 2184, and 2069 bp, respectively, and they encoded four putative proteins (570-676 amino acids) with a molecular mass of ~65.0-76.8 kDa. Quantitative real-time PCR analyses revealed that the four genes were mainly expressed in the hepatopancreas, testis, and hemocytes. SpHc mRNA expression during continuous developmental stages in zoeal phases (Z1, Z2, Z3, Z4, and Z5), megalopa, and juvenile crab I stages were also detected. The expression levels of SpHc3 and SpHc4 were higher than that of SpHc1 and SpHc2 during the first six stages, and they sharply declined during the juvenile stage. After infection with Vibrio parahaemolyticus, the temporal expression of both the four SpHc mRNAs in the megalopa stage rapidly declined during the first 3 h, followed by upregulation and peak expression at 12 h after the challenge. The expression levels of the four SpHc subunits were upregulated at 48 h after the challenge, and were then gradually downregulated. These findings suggest that hemocyanin may potentially be involved in the crab immune response, and that the role of the four subunits may differ in different tissues and during various developmental stages. PMID- 26681012 TI - Result and pedigree analysis of spontaneously abortion villus chromosome detecting by FISH. AB - The aim of this study was to evaluate the relationship between fetal karyotype and parental chromosomal abnormalities, and to provide a basis for clinical diagnosis and therapy in Northeast China. A total of 144 spontaneously aborted fetuses were analyzed by FISH to test for chromosome number and to recall couples for peripheral blood karyotype analysis. The rate of abnormal chorionic villus chromosomes was 35.42%. Villus chromosome abnormality rate of the first spontaneous abortion and repeated abortions were 40.54 and 33.64%, respectively (P < 0.05). The rate of chromosome abnormality in women with advanced maternal age and women younger than 35 years old were 46.43 and 32.76%, respectively (P < 0.05). In a recall of 112 couples for peripheral blood karyotype analysis, just 3 cases of 7 patients with peripheral blood chromosome abnormality showed abnormal FISH results in their abortion villi. Fetal chromosome number abnormality is a major cause of early abortion, and parental chromosomal abnormality is not the main factor in abnormal fetal karyotype. A complete evaluation and special treatment should be provided to couples with a history of recurrent miscarriage. PMID- 26681013 TI - Candidate genes for carcass traits in a tropical-adapted Brazilian composite beef breed. AB - Backfat thickness (BFT) and ribeye area (REA) are important production traits but, because they are measured late in the animal's life, they have not been efficiently included in breeding programs. The aim of this study was to evaluate whether single nucleotide polymorphisms (SNPs) mapped to the leptin, PPARGC1A, PSMC1, CRH, and FABP4 genes, which influence BFT and REA in Canchim cattle, a composite beef breed (5/8 Charolais + 3/8 Zebu). BFT and REA phenotypic records were obtained by ultrasound measurements from 18-month-old animals. All SNP markers were genotyped by restriction fragment length polymorphism-polymerase chain reaction. Restricted maximum likelihood analysis revealed that the non synonymous SNP located in exon 2 of the FABP4 gene has an additive effect on BFT (P <= 0.05). Significant allele substitution effects showed that the substitution of G by A may lead to a decrease of 0.1055 mm in mean BFT. This information can be used for inclusion of this trait-associated marker in commercial SNP panels. PMID- 26681014 TI - Predictive potential role of glutathione S-transferases polymorphisms in response to chemotherapy and breast cancer prognosis. AB - The aim of this study was to evaluate the role of GSTM1 null/present, GSTT1 null/present, and GSTP1 polymorphisms in the clinical response to chemotherapy and treatment outcome of breast cancer. The GSTM1, GSTT1, and GSTP1 IIe105Val polymorphism genotypes were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. Conditional logistic regression analysis revealed that breast cancer patients carrying the GG genotype of GSTP1 IIe105Val showed a significantly better response to chemotherapy compared to those expressing the AA genotype [odds ratio = 2.66, 95% confidence interval (CI) = 1.24-5.91, P = 0.007]. The Cox proportional hazards model indicated that the GG genotype of GSTP1 IIe105Val in breast cancer patients was correlated with a lower risk of death from all causes than those with AA genotype. The adjusted hazard ratio (95%CI) for the GG genotype of GSTP1 IIe105Val was 0.44 (0.18-0.99; P = 0.03). In conclusion, the results of our study indicated that the GG genotype of GSTP1 IIe105Val was significantly associated with better response to chemotherapy and longer overall survival, compared to the wide-type genotype. PMID- 26681015 TI - Serum cytokine modulation after Staphylococcus hyicus infection in BALB/c mice. AB - Staphylococcal infection is a severe bacterial infection. Finding satisfactory predictable biological markers is essential for the treatment of this condition. In this study, we applied a 32-marker sandwich ELISA-based antibody array to evaluate cytokine changes in Staphylococcus hyicus-inoculated BALB/c mice at 24 and 48 h post infection. Among the cytokines detected, the expression levels of granulocyte colony stimulating factor (G-CSF), interleukin 6 (IL-6), macrophage inflammatory protein 2, and keratinocyte chemoattractant (KC) were increased to levels more than twice higher than those in the control group 24 h after infection, while the expression of interleukin 12p40p70 (IL-12p40p70) was decreased to less than half the level measured in the controls. The expression of G-CSF, IL-6, monocyte chemoattractant protei-5, chemokine ligand 11, and KC was upregulated 48 h post infection, whereas IL-12p40p70 expression was still significantly lower (P < 0.05). Among the detected cytokines, the expression levels of G-CSF, IL-6, and KC were constantly upregulated, while IL-12p40p70 was downregulated. This result was then validated by an ELISA assay analysis, which confirmed that G-CSF, IL-6, KC, and IL- 12p40p70 expression levels were specifically modulated after an S. hyicus bacterial infection, while granulocyte monocyte colony stimulation factor, IL-12, and IFNgamma levels were significantly increased after a viral infection. Our study indicated the potential of cytokines G-CSF, IL-6, KC, and IL- 12p40p70 as markers for detecting S. hyicus infection. The results of this study may provide useful data for the appropriate use of medication following S. hyicus infection. PMID- 26681016 TI - New hybrids from peanut (Arachis hypogaea L.) and synthetic amphidiploid crosses show promise in increasing pest and disease tolerance. AB - The primary gene pool of the cultivated peanut (Arachis hypogaea L., allotetraploid AABB) is very narrow for some important characteristics, such as resistance to pests and diseases. However, the Arachis wild diploid species, particularly those from the section Arachis, still have these characteristics. To improve peanut crops, genes from the wild species can be introgressed by backcrossing the hybrids with A. hypogaea. When diploid species whose genomes are similar to those of the cultivated peanut are crossed, sterile hybrids result. Artificially doubling the number of chromosomes of these hybrids results in fertile synthetic polyploids. The objectives of this study were: 1) to obtain progenies by crossing amphidiploids with the cultivated peanut, and 2) to characterize these two groups of materials (amphidiploids and progenies) so that they may be efficiently conserved and used. Using morphological, molecular, and pollen viability descriptors we evaluated one cultivar of A. hypogaea (IAC 503), eight synthetic amphidiploids, and the progenies resulting from four distinct combinations of crossing between IAC 503 and four amphidiploids. PMID- 26681017 TI - Influence of gender on ABCC2 expression in peripheral blood mononuclear cells. AB - It is known that several factors, including gender, may influence the expression of multidrug resistance associated proteins 2 (MRP2/ABCC2) in the peripheral blood mononuclear cells (PBMCs). This study aims to compare ABCC2 gene expression in PBMCs of healthy males and females. PBMCs were extracted from 48 females and 44 males, and gene expression was measured using real-time quantitative polymerase chain reaction (real-time QPCR). Multiple housekeeping genes (Actin beta, beta2-M, GAPDH) were utilized as endogenous controls. The stability of housekeeping genes was verified using the Excel-based Bestkeeper(r) program. Our results showed that expression level of ABCC2 in PBMCs was 1.2-1.4 fold higher in males compared to that in females, depending on the endogenous control(s) used. However, this difference was not statistically significant. When considering using a single endogenous control gene, GAPDH and Actin-betawere found to be more suitable than beta2-M. Moreover, GAPDH + Actin-beta, or the combination of all three housekeeping gene as endogenous control(s) showed greater stability than other endogenous control genes for normalization of ABCC2 expression in PBMCs. This study suggests that ABCC2 expression in PBMCs may be, in part, influenced by gender, and that at least two endogenous control genes should be utilized for gene expression normalization. PMID- 26681018 TI - Bos taurus papillomavirus activity in peripheral blood mononuclear cells: demonstrating a productive infection. AB - Bovine papillomavirus (BPV) is an oncogenic virus with mucous and epithelial tropism. Possible productive virus infection in other tissues, such as blood, has been hypothesized. In order to investigate this possibility, three samples of skin papillomas and blood were collected from bovines with BPV infection and five samples of peripheral blood and one sample of normal tissue were collected from a calf without BPV infection. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and examined by reverse transcription-polymerase chain reaction, immunofluorescence, in situ hybridization, and electron microscopy. The tissue samples were examined for histopathological and immunohistochemical features. The skin papillomas showed the presence of DNA sequences of BPV-2, BPV 11, and a putative virus type. The blood samples showed DNA sequences of BPV-1, 2, and 4 simultaneously. Immunohistochemistry showed BPV L1 protein in both epithelium and stroma and BPV E2 protein in koilocytes. In situ hybridization confirmed the presence of BPV DNA in PBMCs and immunofluorescence showed nuclear labeling of E2 and L1 BPV proteins in PBMCs. The transcription analysis revealed transcripts of BPV-1 L1, BPV-2 L2, and BPV-4 E7 in blood and papilloma samples of BPV-infected cattle. The comet assay revealed high levels of host cell DNA damage upon BPV infection. Electron microscopy analysis of PBMCs identified the presence of particles in the cytoplasm that are consistent with papillomavirus in size and shape. The productive infection of PBMCs with BPV has been previously discussed and this study provides evidence indicating that PBMCs are a target of BPV. PMID- 26681019 TI - Effect of isodillapiole on the expression of the insecticide resistance genes GSTE7 and CYP6N12 in Aedes aegypti from central Amazonia. AB - The yellow fever mosquito Aedes (Stegomyia) aegypti is the main vector of dengue arbovirus and other arboviruses. Dengue prevention measures for the control of A. aegypti involve mainly the use of synthetic insecticides. The constant use of insecticides has caused resistance in this mosquito. Alternative studies on plant extracts and their products have been conducted with the aim of controlling the spread of the mosquito. Dillapiole is a compound found in essential oils of the plant Piper aduncum (Piperaceae) which has been effective as a biopesticide against A. aegypti. Isodillapiole is a semisynthetic substance obtained by the isomerization of dillapiole. In the present study, isodillapiole was evaluated for its potential to induce differential expression of insecticide resistance genes (GSTE7 and CYP6N12) in 3rd instar larvae of A. aegypti. These larvae were exposed to this compound at two concentrations (20 and 40 MUg/mL) for 4 h during four generations (G1, G2, G3, and G4). Quantitative RT-PCR was used to assess the expression of GSTE7 and CYP6N12 genes. GSTE7 and CYP6N12 relative expression levels were higher at 20 than at 40 MUg/mL and varied among generations. The decrease in GSTE7 and CYP6N12 expression levels at the highest isodillapiole concentration suggests that larvae may have suffered from metabolic stress, revealing a potential alternative product in the control of A. aegypti. PMID- 26681020 TI - Bioequivalence of clopidogrel hydrogen sulfate tablets in healthy Chinese volunteers. AB - We aimed to evaluate the bioequivalence of clopidogrel in healthy Chinese volunteers after administration of a single oral dose. We administered a single oral dose of 75 mg clopidogrel (test and reference) to 32 healthy Chinese volunteers according to an open, randomized, crossover design. The concentration of clopidogrel acid (carboxylic metabolite of clopidogrel) in the plasma was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioequivalence of the test and reference preparations were calculated using analysis of variance and one-sided t-test by using the DAS 2.0 software. The pharmacokinetic parameters of the test and reference preparations were as follows: peak plasma concentration (Cmax), 1351.101 +/- 654.955 ng/mL and 1184.652 +/- 607.713 ng/mL; area under the curve, 2642.017 +/- 1093.848 ng.h/mL and 2780.666 +/- 1283.100 ng.h/mL; and time to reach Cmax (Tmax), 0.789 +/- 0.318 h and 0.953 +/- 0.633 h, respectively. The relative bioavailability of the formulation was 101.7 +/- 35.3%, which indicated that the test preparation was bioequivalent to the reference drug. PMID- 26681021 TI - Effects of HIF prolyl-hydroxylase-2 gene silencing on HCG-induced vascular endothelial growth factor expression in luteal cells. AB - Vascular endothelial growth factor (VEGF)-dependent angiogenesis plays a crucial role in corpus luteum formation and its functional maintenance in mammalian ovaries. We recently reported that activation of hypoxia-inducible factor (HIF) 1alpha signaling contributes to the regulation of VEGF expression in luteal cells (LCs) in response to human chorionic gonadotropin (HCG). We examined whether HIF prolyl-hydroxylase (PHD)-2 gene silencing induces VEGF expression in LCs and enhanced its expression induced by HCG in LCs. Using real-time polymerase chain reaction and western blot analysis, we measured the expression of PHD-2 to confirm plasmid PHD-2 shRNA transfection and protein expression and investigated the changes in HIF-1a and VEGF expression after treatment with HCG and PHD-2 shRNA transfection. After PHD-2 shRNA transfection, PHD-2 expression was significantly lower than that in control groups with or without HCG treatment, while a significant increase in VEGF mRNA was observed compared to in controls, indicating that PHD-2 plays an important role in VEGF regulation. Additionally, changes in VEGF mRNA expression were consistent with the expression levels of HIF 1a protein, not HIF- 1a mRNA, which is regulated by HIF prolyl-hydroxylase mediated degradation. Our results indicate that PHD-2 gene silencing can induce VEGF expression in LCs and HCG-induced VEGF expression can be further enhanced by PHD-2 gene silencing through an HIF-1a-mediated mechanism in LCs. This PHD-2 mediated transcriptional activation may be important for regulating VEGF expression through HIF-1a signaling in LCs during corpus luteum development in mammals. PMID- 26681022 TI - Isolation and characterization of Calcineurin B-like gene (PbCBL1) and its promoter in birch-leaf pear (Pyrus betulifolia Bunge). AB - Calcium plays a critical role in regulating abiotic stress responses in plants. Calcineurin B-like (CBL) proteins are calcium sensors in calcium signaling pathways. However, the molecular mechanisms underlying calcium signaling remain to be elucidated. In this study, the CBL1 gene, which codes for the CBL protein, was isolated from the birch-leaf pear. One 2,969-bp sequence was cloned using PCR, and using the cloned 2,027-bp sequence was isolated from pear genomic DNA via genome walking. Sequencing analysis revealed that the 4,996-bp sequence was a PbCBL1 gene consisting of eight exons and seven introns, and the 2,027-bp sequence was identified as the promoter of the PbCBL1 gene, which contains the basic promoter elements TATA and CAAT boxes. In addition, some other cis-acting elements including heat, cold, drought, and hormone responsive elements were also present. To further investigate the activity of this promoter, the sequence was used to drive a GUS fusion gene into leaf discs of tobacco (Nicotiana benthamiana) with Agrobacterium-mediated transformation method. GUS gene expression could be regulated by the PbCBL1 promoter following induction by GA, ABA, SA, and MeJA. Furthermore, the results of real-time RT-qPCR indicate that the PbCBL1 gene can respond to changes in the intracellular calcium concentration, and that it can be induced by cold, heat, drought, and stress by several hormones including GA, ABA, SA, and MeJA. PbCBL1 gene may be involved in several signal transduction pathways, and play an important role in the condition of adversity stress in pear. PMID- 26681023 TI - Decreased miR-134 expression and its tumor-suppressive function in human osteosarcoma. AB - Dysregulation of microRNA (miR) is often associated with cancer development and progression. Aberrant expression of miR-134 has been found in some types of cancer. However, its expression and function in osteosarcoma remain unclear. The aim of this study was to explore the effects of miR-134 in osteosarcoma tumorigenesis and development. The expression level of miR-134 was quantified by real-time reverse transcription-polymerase chain reaction in human osteosarcoma cell lines and tissues. The effects of miR-134 on MG-63 cell phenotypes and tumorigenicity in vivo were observed using flow cytometry, 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, migration, and scratch migration assays. MiR-134 was significantly downregulated in osteosarcoma cell lines and clinical specimens. Decreased miR-134 expression was significantly associated with large tumor size, positive distant metastasis, and advanced clinical stage. Low miR-134 expression in osteosarcoma was an independent predictor of poor survival. Overexpression of miR-134 inhibited MG-63 cell proliferation, invasion, and migration, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. These findings indicate that miR-134 may act as a tumor suppressor in osteosarcoma and could serve as a novel therapeutic agent for miRNA-based therapy. PMID- 26681024 TI - Cloning, characterization, and expression of cadmium-induced metallothionein-2 gene from earthworm Pheretima aspergillum (E. Perrier). AB - Metallothioneins (MTs) are ubiquitous metal-binding, cysteine-rich proteins, associated with metal accumulation and thus providing protection against toxic heavy metals such as cadmium (Cd). To investigate the mechanisms of enrichment of Cd in the earthworm Pheretima aspergillum, we isolated and cloned metallothionein 2 (MT-2) cDNA (538 bp) from P. aspergillum, analyzed its sequence, and examined MT-2 transcription levels by relative quantitative real-time PCR under different concentrations of Cd. The sequence of P. aspergillum MT-2 cDNA and its putative amino acid sequence were highly similar to sequences from other earthworms. The induction with Cd increased the MT-2 gene transcription level in a dose-dependent manner. In addition, earthworm recombinant MT-2 exhibited high Cd bioaccumulation ability in vitro. These results suggested that MT-2 plays an important role in tolerance and accumulation of Cd in P. aspergillum. PMID- 26681025 TI - Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria. AB - KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors. PMID- 26681026 TI - Translation of foot-and-mouth disease virus RNA: factors influencing alternative AUG selection. AB - The mechanism of alternative AUG usage in foot-and-mouth disease virus is not completely understood. Using simple computational approaches, we evaluated the contributions of overall codon bias, quantitative codon bias, and %GC of the region between the two alternative AUGs, Region-La, as well as the nucleotide bias of the sequence context flanking each AUG with respect to translation initiation efficiency. For all serotypes of this virus, we found that only a small component of the effect of RNA secondary structure on ribosome scanning was due to the low %GC of Region-La. In addition, we found that the nucleotide bias of the context from position -4 to +6 flanking the AUG(2nd) had a negative correlation with the overall codon bias, and that a strong purine bias existed in this AUG(2nd)context. However, the quantitative codon bias of Region-La was seen to be significantly lower than that of Region-Lb (the sequence following AUG(2nd)) in all serotypes except SAT 1-3. Taken together, our results suggest that the low codon bias of Region-La might impair the translation initiation efficiency at the AUG(1st) in all serotypes except SAT 1-3, and the specific AUG(2nd) context might be used as a strong signal to initiate translation from the AUG(2nd) in all serotypes. PMID- 26681027 TI - Correlations between the COMT gene rs4680 polymorphism and susceptibility to ovarian cancer. AB - The objective of this study was to perform a systematic review of the correlations between the single nucleotide polymorphism rs4680 in the catechol-O methyltransferase (COMT) gene and susceptibility to ovarian cancer. A computer search was carried out for relevant case-control studies published between January 2000 to January 2014 in databases such as Ovid, EBSCO, PubMed, CNKI, CBMDISC, VIP, and WanFang Data. The literature was screened based on inclusion and exclusion criteria. A meta-analysis was performed by calculating the combined odds ratios (OR) and 95% confidence intervals (CI) using the RevMan 5.0. A total of 7 case-control studies were selected, which included 1439 cases and 2927 control subjects. Meta-analysis showed that the rs4680 polymorphism was not associated with ovarian cancer [GG vs (GA+AA): OR = 1.02, 95%CI = 0.88-1.19; G vs A allele: OR = 1.0, 95%CI = 0.90-1.11]. We, therefore, conclude that the COMT rs4680 polymorphism is not associated with susceptibility to ovarian cancer. PMID- 26681028 TI - Expression and prognostic influence of NF-kappaB and EGFR in esophageal cancer. AB - The goal of this study was to investigate the expression profiles of nuclear factor-kappa B (NF-kappaB) and epidermal growth factor receptor (EGFR) in esophageal cancer and to determine their association with tumor prognosis. This study included 40 esophageal cancer patients [22 men and 18 women; average age = 62.7 +/- 3.9 years; tumor-node-metastasis (TNM) staging: 12 patients with stage I, 13 patients with stage II, and 15 patients with stage III disease]. Tumor tissues and tumor-adjacent tissue specimens were collected during radical resections at our hospital. Immunohistochemical staining was used to examine these tissues for NF-kappaB and EGFR expression. Follow-up of all patients included gathering information such as the 3-year survival rate. We found that NF kappaB and EGFR expression was significantly higher in tumor tissues compared to tumor-adjacent normal tissues. Expression was not related to gender or age, but was positively associated with the degree of tumor infiltration. NF-kappaB and EGFR expression levels gradually increased with higher TNM stage, but this difference was not significant. Follow-up results showed that patients with higher NF-kappaB and EGFR levels had a lower survival rate and unfavorable prognosis. In conclusion, we found that NF-kappaB and EGFR expression was significantly elevated during the occurrence and development of esophageal carcinoma, and expression of these factors appears to be correlated with cancer progression. Higher expression of both genes is associated with an unfavorable prognosis. PMID- 26681029 TI - Genetic variation in Rhodomyrtus tomentosa (Kemunting) populations from Malaysia as revealed by inter-simple sequence repeat markers. AB - Kemunting (Rhodomyrtus tomentosa) from the Myrtaceae family, is native to Malaysia. It is widely used in traditional medicine to treat various illnesses and possesses significant antibacterial properties. In addition, it has great potential as ornamental in landscape design. Genetic variability studies are important for the rational management and conservation of genetic material. In the present study, inter-simple sequence repeat markers were used to assess the genetic diversity of 18 R. tomentosa populations collected from ten states of Peninsular Malaysia. The 11 primers selected generated 173 bands that ranged in size from 1.6 kb to 130 bp, which corresponded to an average of 15.73 bands per primer. Of these bands, 97.69% (169 in total) were polymorphic. High genetic diversity was documented at the species level (H(T) = 0.2705; I = 0.3973; PPB = 97.69%) but there was a low diversity at population level (H(S) = 0.0073; I = 0 .1085; PPB = 20.14%). The high level of genetic differentiation revealed by G(ST) (73%) and analysis of molecular variance (63%), together with the limited gene flow among population (N(m) = 0.1851), suggests that the populations examined are isolated. Results from an unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis clearly grouped the populations into two geographic groups. This clear grouping can also be demonstrated by the significant Mantel test (r = 0.581, P = 0.001). We recommend that all the R. tomentosa populations be preserved in conservation program. PMID- 26681030 TI - Improved Agrobacterium-mediated transformation and high efficiency of root formation from hypocotyl meristem of spring Brassica napus 'Precocity' cultivar. AB - Rape seed (Brassica napus L.) is one of the most important oil seed crops in the world. Genetic manipulation of rapeseed requires a suitable tissue culture system and an efficient method for plant regeneration, as well as an efficient transformation procedure. However, development of transgenic B. napus has been problematic, and current studies are limited to cultivated varieties. In this study, we report a protocol for regeneration of transgenic rape after Agrobacterium-mediated transformation of hypocotyls from the spring B. napus 'Precocity' cultivar. We analyzed the effects of plant growth regulators in the medium on regeneration. Additionally, factors affecting the transformation efficiency, including seedling age, Agrobacterium concentration, infection time, and co-cultivation time, were assessed by monitoring GUS expression. Results from these experiments revealed that transformation was optimized when the meristematic parts of the hypocotyls were taken from 8 day-old seedlings, cultured on Murashinge and Skoog basal media containing 0.1 mg/L 1 naphthaleneacetic acid and 2.5 mg/L 6-benzylaminopurine, and incubated in Agrobacterium suspension (OD600 = 0.5) for 3 to 5 min, followed by 2 days of co cultivation. Integration of T-DNA into the plant genome was confirmed by polymerase chain reaction (PCR), b-glucuronidase histochemical staining, and quantitative real-time PCR. The protocols developed for regeneration, transformation, and rooting described in this study could help to accelerate the development of transgenic spring rape varieties with novel features. PMID- 26681031 TI - Meta-analysis of the association between the rs7903146 polymorphism at the TCF7L2 locus and type 2 diabetes mellitus susceptibility. AB - Type 2 diabetes mellitus (T2DM) is a chronic disease caused by genetic and environmental factors. T2DM has been associated with specific polymorphisms in the TCF7L2 gene. This study evaluates the relationship between the rs7903146 locus polymorphism of the TCF7L2 gene and T2DM susceptibility through meta analysis; the overall aim is to provide a basis for evidence-based medicinal treatment of T2DM. Cohort and case-control studies from Medline, PubMed, EMBASE, CBM, CNKI, and academic conferences/dissertations that examined the correlation between T2DM and rs7903146 polymorphisms were evaluated. We determined whether the TCF7L2 rs7903146 locus was associated with T2DM susceptibility by comparing alleles and genotypes. The Stata 11.0 software was applied for meta-analysis, and a random-effects model was adopted for heterogeneity testing and odds ratio (OR) calculation. A fixed-effect model was used for quantitative analysis of the heterogeneity between different studies, and for calculating the percentage of variability I(2). A total of 10 studies related to the rs7903146 loci and T2DM susceptibility were enrolled; this included 3404 cases of T2DM patients and 6473 control cases. Meta-analysis showed that the T allele of rs7903146 was significantly correlated with the risk of T2DM, with both a dominant fixed-effect model (OR = 1.653, 95%CI = 1.416-1.653) and a co-dominant-fixed effect model (OR = 1.525, 95%CI = 1.350-1.723). Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility. PMID- 26681032 TI - Frequency of glutathione-S-transferase null-M1 and null-T1 genotypes among the Turabah population in Saudi Arabia. AB - Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in protection against products of oxidative stress and against electrophiles. Glutathione S-transferase mu (GST-M1) and theta (GST-T1) are isoforms of glutathione transferase enzymes that participate in the metabolism of a wide range of chemicals. Deletion variants that are associated with a lack of enzyme function exist at both these loci. The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are very high in most of the populations studied to date. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 genotypes among the Turabah population in Saudi Arabia in comparison with the data published for some other Arabic populations. The subjects consisted of 164 unrelated healthy individuals from the Turabah population. GST genotyping was performed by multiplex polymerase chain reaction-based methods. The GSTM1 deletion homozygosity was 56.1% and GSTT1 deletion homozygosity was 20.7%, while the GSTM1 and GSTT1 double-deletion homozygosity was 11.0%. Comparison with published data from Bahraini, Lebanese, and Tunisian populations demonstrated no significant difference for GSTM1 between these populations. The GSTT1 null-allele frequency was significantly lower than those for the Lebanese and Tunisian populations (P = 0.001) but similar to that for the Bahraini population (P = 0.099). Characterization of GST genetic polymorphisms in the Saudi population may aid in genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and the pharmacogenetics of chemotherapy. PMID- 26681033 TI - MicroRNA-26b inhibits osteosarcoma cell migration and invasion by down-regulating PFKFB3 expression. AB - MicroRNAs regulate target gene expression and are involved in cell proliferation, apoptosis, differentiation, tumor invasion, and cancer stem cell regulation, among other processes. MicroRNA-26b (miR-26b) is closely related to tumor occurrence and development. In this study, we analyzed miR-26b expression in osteosarcoma tissue, its effect on Saos-2 osteosarcoma cell proliferation and invasion, and its relationship with 6-phosphofructo-2-kinase/fructose-2,6 biphosphatase 3 (PFKFB3) expression. Osteosarcoma tissue was obtained from surgical patients and normal tissue adjacent to the tumor was used as a control. Real-time polymerase chain reaction was applied to detect miR-26b expression in cancer tissue and normal tissue. A vector expressing miR-26b was constructed and transfected into Saos-2. An MTT assay, cell invasion assay, and scratch experiment were used to analyze the effect of miR-26b on Saos-2 cell proliferation, invasion, and migration abilities. Western blotting analysis was performed to investigate the role of miR-26b on PFKFB3 expression. miR-26b expression in normal tissue was 7.55-fold higher than in osteosarcoma tissue (t = 10.20, P = 0.006). Compared with control tissue, miR-26b significantly inhibited osteosarcoma proliferation, migration, and invasion (P < 0.05). Western blotting results revealed that PFKFB3 protein expression decreased in Saos-2 cells after transfection with miR-26b. miR-26b was down-regulated in osteosarcoma tissue. miR 26b may inhibit osteosarcoma cell proliferation, migration, and invasion by regulating PFKFB3 protein expression. miR-26b may have a tumor suppressor role in tumor occurrence and development. PMID- 26681034 TI - Association between the -607 C > A polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis. AB - The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions. PMID- 26681035 TI - Absence of the BaeR protein leads to the early initiation of DNA replication in Escherichia coli. AB - Escherichia coli cells have dozens of two-component systems to sense and respond to various stimuli, and thereby cope with changing environments. BaeS/BaeR is one such two-component system, and it deals with a variety of envelope stresses. Interestingly, the ArcA/ArcB and TorS/TorR two-component systems are known to be associated with initiation of DNA replication; however, the effects of BaeS/BaeR on initiation of DNA replication remain unknown. Flow cytometry analysis revealed that the average number of replication origins (oriCs) per cell in DeltabaeR mutants was approximately 30% higher than that in wild-type cells. So was the growth rate of DeltabaeR cells. Ectopic expression of BaeR from the pbaeR plasmid reversed the DeltabaeR mutant phenotypes. The results indicate that absence of BaeR leads to the early initiation of DNA replication. Further, deletion of BaeR caused an increase in the amount of DnaA per cell, but did not change concentration of DnaA, which is the initiator protein.The average number of oriCs per cell in Deltaspy mutants was the same as that found in the wild-type cells although spy gene expression is controlled by BaeR. These results suggest that BaeR may indirectly affect initiation of replication by controlling expression of the dnaA gene. PMID- 26681036 TI - Meta-analysis of the relationship between slow acetylation of N-acetyl transferase 2 and the risk of bladder cancer. AB - The incidence of bladder cancer is closely associated with exposure to aromatic amines, that can cause cancer only after metabolic activation regulated by N acetyl transferase 1 and 2 (NAT1 and NAT2). Many studies have indicated that slow acetylation of NAT2 increases the risk of bladder cancer. The major risk factor is tobacco smoke; however, some studies have failed to prove this. This study attempted to explore the correlation between NAT2 slow acetylation and bladder cancer risk through a meta-analysis of published case-control studies. Studies detecting NAT2 gene status in bladder cancer patients and healthy controls were retrieved from PubMed, Cochrane, EMchrane, CBM, and CNKI. We retrieved the data of cited articles and publications to identify and compare NAT2 gene in bladder cancer patients and healthy controls. The variables within and between the studies were also considered. The META module in the Stata v.6.0 software was used for data analysis. Twenty independent studies were enrolled in our meta analysis according to the inclusion and exclusion criteria. Individual differences in the bladder cancer susceptibility were, in part, attributed to the effect of carcinogens. The merged odds ratio of the effect of slow acetylation on bladder cancer was 1.31 (95% confidence interval = 1.11-1.55). In conclusion, NAT2 slow acetylation state was associated with bladder cancer risk, and was shown to modestly increase the risk of bladder cancer. PMID- 26681037 TI - Blockage of cisplatin-induced autophagy sensitizes cervical cancer cells to cisplatin. AB - Development of chemoresistance is a major obstacle that leads to the recurrence and progression of cervical cancer (CC). Autophagy, meaning, "eating of self", has shown paradoxical functions in tumors. In this study, we first investigated the process of autophagy induction by cisplatin in CC cells. Next, we investigated the role of autophagy in cisplatin-sensitivity of CC cells via blockage of cisplatin-induced autophagy. The results demonstrated that cisplatin induces autophagy in CC HeLa cells via upregulating the formation of autophagic vesicle, promoting the conversion of LC-I to LC-II, and increasing the expression of autophagy-related gene 7 (Atg-7). On the other hand, the autophagy inhibitor, 3MA, downregulated cisplatin-induced formation of autophagic vesicles, reduced the conversion of LC-I to LC-II, and decreased Atg-7 expression. Moreover, 3MA reversed the reduction in cellular viability and induction of apoptosis by cisplatin in HeLa cells. Our results imply that autophagy blockage may play a key role in the chemosensitivity of cervical cancers. PMID- 26681038 TI - Association of a let-7 KRAS rs712 polymorphism with the risk of breast cancer. AB - Breast cancer (BC) is a common malignancy affecting women, with increasing incidences of this disease in China every year. Recent studies have extensively investigated a single nucleotide polymorphism in the let-7 miRNA binding site of the 3'-untranslated region of KRAS mRNA. The aim of this study was to determine the genotype frequency of the KRAS rs712 polymorphism, and evaluate its effect on BC risk. This hospital-based case-control study comprised 228 patients with histologically confirmed BC and 251 healthy controls. The let-7a KRAS rs712 polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. We observed no statistically significant association between BC risk and the let-7a KRAS rs712 polymorphism (GT vs GG, OR = 0.98, 95%CI = 0.66 1.46; TT vs GG, OR = 0.78, 95%CI = 0.28-2.21). However, the rs712 polymorphism was significantly associated with the N status of BC patients (GG vs GT/TT, OR = 0.52, 95%CI = 0.30- 0.92; G allele vs T allele, OR = 0.60, 95%CI = 0.37-0.97). We found no association between the let-7 rs712 polymorphism and BC risk. However, the let-7 rs712 G/T polymorphism was discovered to play a potential role in BC tumor metastasis; therefore, it may be employed as a new biomarker or therapy targeted towards resistant tumor metastasis. PMID- 26681039 TI - Association of the interleukin-6 gene -572G/C polymorphism with cancer risk: a meta-analysis. AB - The -572G/C polymorphism in interleukin-6 (IL-6) gene is associated with the development of cancer. However, previous studies have shown conflicting results; therefore, the association must be verified by an appropriate meta-analysis. For this purpose, we performed a literature search of the PubMed database to identify all reports on association between the IL-6 -572G/C polymorphism and cancer risk. Summary odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the -572G/C polymorphism and cancer in a fixed- and random-effect model, as appropriate. Publication bias was evaluated using the Begg's funnel plot. The meta-analysis was performed on the STATA (v.12.0) software. Seven studies, which analyzed 3387 cases and 4529 controls, were identified. The results of the meta analysis showed no significant association between the -572G/C polymorphism in the IL-6 gene and cancer risk (GG vs CC: OR = 1.03, 95%CI = 0.76-1.40; GG vs CG: OR = 0.94, 95%CI = 0.82-1.09; dominant model: OR = 1.06, 95%CI = 0.92-1.21; recessive model: OR = 1.01, 95%CI = 0.86-1.18). The data were subjected to a subgroup analysis (stratified by race and cancer type), and no significant associations were found between the -572G/C polymorphism in the IL-6 gene and cancer risk. Therefore, the results of this meta-analysis suggested that the IL-6 -572G/C polymorphism was not associated with an elevated risk of cancer. PMID- 26681040 TI - Effects of Danhong injection on hemodynamics and the inflammation-related NF kappaB signaling pathway in patients with acute cerebral infarction. AB - The objective of the current study was to investigate effects of Danhong injection on hemodynamics, inflammatory cytokines, and the NF-kappaB pathway in acute cerebral infarction. In total, 246 patients with acute cerebral infarction were divided into control (N = 121) and observation (N = 125) groups based on treatment. The control group underwent conventional treatment, while the observation group was treated with conventional medicine and Danhong injection. Fourteen days later, the curative effect, hemorheology, mRNA, and protein levels of inflammatory cytokines (IL-6, TNF-alpha, and IL-1beta) in peripheral white blood cells, and changes in the NF-kappaB signaling pathway were analyzed. The observation group had a significantly higher curative effect compared to the control group. The hemodynamic indices (high shear viscosity, low shear viscosity, plasma viscosity, hematocrit, platelet aggregation rate, and erythrocyte aggregation index) were significantly improved in both groups, although changes were more remarkable in the observation group. Peripheral white blood cells from patients in the observation group had significantly lower mRNA and protein levels of inflammatory cytokines IL-6, TNF-alpha, and IL-1beta after treatment compared to cells from patients in the control group. NF-kappaB p65 in the cytoplasm of peripheral blood cells of the observation group increased significantly after treatment compared to that of the control group, while nuclear NF-kappaB p65 decreased compared to that in the control group. In conclusion, Danhong injection has a significant curative effect on patients with acute cerebral infarction, lowers inf?lammation, and improves hemodynamic changes; therefore, it is worth clinical application. PMID- 26681041 TI - Hepatic phosphoenolpyruvate carboxykinase expression after gastric bypass surgery in rats with type 2 diabetes mellitus. AB - The objective of this study was to investigate the mRNA expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) after gastric bypass surgery (GBS) in rats with type 2 diabetic mellitus (T2DM). Thirty-six male Goto-Kakizaki rats, aged 12 weeks, were randomly divided into the GBS, sham operation with diet restriction (SO), and sham operation alone (control) groups (N = 12 per group). Liver specimens from all rats were obtained during the operation and 8 weeks after operation. Blood lipid levels were measured before and 8 weeks after operation. Fasting blood glucose (FBG), food intake, and body weight were recorded at weekly time points after operation. The blood glucose area under the curve (AUC) was calculated, and insulin sensitivity indices (ISI) were assessed. The expression PEPCK mRNA and protein were measured by real-time polymerase chain reaction and western blot. Compared with those of the SO and control groups, the blood lipid levels and the FBG in the GBS group was significantly decreased (P < 0.05), as was the AUC (P < 0.05), whereas the ISI was significantly increased (P < 0.05). PEPCK mRNA and protein levels in the GBS group were lower than those in the control group, whereas those in the SO group were significantly higher than those in controls (P < 0.05). In conclusion, GBS can reduce blood glucose in T2DM rats while improving glucose tolerance and hyperglycemia, and the mechanism appears to be associated with a decrease of hepatic PEPCK mRNA and protein expression. PMID- 26681042 TI - Deep sequencing-based analysis of gene expression in bovine mammary epithelial cells after Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae infection. AB - The goal of this study was to characterize the transcriptome of primary bovine mammalian epithelial cells (pBMECs) and to identify candidate genes for response and resistance to Staphylococcus aureus (strain S108), Escherichia coli (strain E23), and Klebsiella pneumoniae (strain K96) infection. Using Solexa sequencing, approximately 4.9 million total sequence tags were obtained from each of the three infected libraries and the control library. Gene Ontology (GO) analysis of the S108-infected pBMECs showed differentially expressed genes (DEGs) were significantly involved in metabolic processes. In E23-infected pBMECs, DEGs were predominantly associated with cell death and programmed cell death GO terms, while in K96-infected pBMECs, DEGs were primarily involved in metabolic processes and in utero embryonic development. Analysis of the cluster of orthologous groups of proteins showed that the S108-infected, E23-infected and K96-infected pBMECs were significantly involved in "Translation, ribosomal structure and biogenesis", "General function prediction only" and "Replication, recombination and repair". The transcriptome sequences were also annotated for KEGG orthology, and it was found that DEGs in S108-infected pBMECs were significantly involved in oxidative phosphorylation and Parkinson's disease. The clustered pathway terms of the DEGs of the E23-infected pBMECs were found to involve the NOD-like receptor signaling pathway and oxidative phosphorylation, while those of the K96-infected pBMECs were primarily involved in oxidative phosphorylation and apoptosis. Our results have identified a number of immune-related genes that showed changes in gene expression after bacterial infection, and provided insight into the interactions between pBMECs and the bacteria. PMID- 26681044 TI - Construction and characterization of a bacterial artificial chromosome library for the allotetraploid Gossypium tomentosum. AB - Gossypium tomentosum is a wild allotetraploid species with the (AD)5 genome. It is characterized by many useful traits including finer fiber fineness, drought tolerance, and Fusarium and Verticillium resistance. We constructed the first bacterial artificial chromosome library for Gossypium tomentosum. With high quality and broad coverage, this library includes 200,832 clones, with an average insert size of about 122 kb and fewer than 3% empty clones. Our library is approximately 10-fold the size of the (AD)5-genome (2400 Mb) and provides a 99.7% probability of isolating genes of interest or their sequences. Seven of eight simple sequence repeats markers that are located on five different chromosomes and linked with resistance to Verticillium wilt could amplify the 50 superpools and obtained one to five hits. This high capacity library will be an important genomic resource for classifying and analyzing the evolution of allotetraploid cotton species as well as for isolating disease-resistance and drought-tolerance genes. PMID- 26681043 TI - Genetic structure of Pilosocereus gounellei (Cactaceae) as revealed by AFLP marker to guide proposals for improvement and restoration of degraded areas in Caatinga biome. AB - Amplified fragment length polymorphism (AFLP) analysis was used to evaluate DNA polymorphism in Pilosocereus gounellei with the aim of differentiating samples grown in different Brazilian semiarid regions. Seven primer pairs were used to amplify 703 AFLP markers, of which 700 (99.21%) markers were polymorphic. The percentage of polymorphic markers ranged from 95.3% for the primer combination E AAG/M-CTT to 100% for E-ACC/M-CAT, E-ACC/M-CAA, E-AGC/M-CAG, E-ACT/M-CTA, and E AGG/M-CTG. The largest number of informative markers (126) was detected using the primer combination E-AAC/M-CTA. Polymorphism of the amplified DNA fragments ranged from 72.55% (in sample from Piaui State) to 82.79% (in samples from Rio Grande Norte State), with an average of 75.39%. Despite the high genetic diversity of AFLP markers in xiquexique, analysis using the STRUCTURE software identified relatively homogeneous clusters of xiquexique from the same location, indicating a differentiation at the molecular level, among the plant samples from different regions of the Caatinga biome. The AFLP methodology identified genetically homogeneous and contrasting plants, as well as plants from different regions with common DNA markers. Seeds from such plants can be used for further propagation of plants for establishment of biodiversity conservation units and restoration of degraded areas of the Caatinga biome. PMID- 26681045 TI - Investigation of polymorphisms in anti-inflammatory cytokine genes in hematogenous osteomyelitis. AB - Osteomyelitis is a progressive bone infection disease caused by destructive immunological inflammatory reactions following new bone formation. Anti inflammatory cytokines are a series of immunoregulatory molecules that control the pro-inflammatory cytokine response. In this study, we investigated 9 single nucleotide polymorphisms in 5 different cytokine/cytokine receptor genes in hematogenous osteomyelitis (HO) patients, and compared their outcomes with normal healthy individuals. Sequence-specific forward and reverse primers and two TaqMan(r) MGB probes with dyes (VICTM and FAMTM) that specifically detect Allele 1 and Allele 2 of each SNP were utilized. The genotypes CC (P = 0.009) and CT (P = 0.041) of SNP rs2070874, and alleles A (P = 0.044) and G of SNP rs1800871 were significantly different between the patients and healthy controls. The expression of the CC genotype or C allele at rs2070874 was a risk factor for HO development, with higher frequencies of CT and T being found in the control samples. The expression of the A allele of rs1800871 was also significantly higher in patients than in controls, and was therefore considered a risk factor. PMID- 26681046 TI - Diversity and structure of a bacterial community in grassland soils disturbed by sheep grazing, in the Loess Plateau of northwestern China. AB - The relationship between disturbance, biodiversity, and ecosystem function has been a hot topic recently in international ecological research, and a universally applicable model remains elusive. In this study, we assessed the diversity and structure of a bacterial community in grassland soils along a disturbance gradient due to sheep grazing. Bacteria were identified based on 16S rDNA gene libraries prepared from a 12-year field experiment that included four grazing, intensity treatments: no grazing, light grazing, moderate grazing and heavy grazing in the Loess Plateau of northwestern China. We found that diversity indices of bacterial 16S rDNA increased with grazing intensity, suggesting that disturbance led to higher bacterial diversity. The bacterial community structure, measured as species composition, was also affected by grazing. In addition, the change in soil bacterial community composition was maximum under heavy grazing, based on the Sorensen similarity index. Overall, the relationship between disturbance and bacterial diversity is complex, therefore, more studies are required to determine the possibility of using microbial diversity as an indicator of ecosystem stability. PMID- 26681047 TI - Correlation between sperm ultrastructure in infertile patients with abnormal sperm morphology and DNA damage. AB - This study explored the correlation between sperm ultrastructure in infertile patients with abnormal sperm morphology and DNA damage. Three unusual sperm morphologies were selected for the experimental group namely case 1 (95% headless sperm), case 2 (98% headless sperm), and case 3 (100% headless sperm), and the control group consisted of 2 subjects (20 and 15% headless sperm). For case 1, the patient was negative for sexually transmitted diseases and had normal semen plasma biochemistry, reproductive hormones, peripheral blood chromosomes, and azoospermia factor (AZF). The aneuploid rate of sperm chromosomes was 0.6%, and DNA damage index of sperm nuclei was 84.4%. The partner of this patient did not get pregnant after artificial reproductive technology assistance. For case 2, the aneuploid rate of sperm chromosomes was 0.8% and DNA damage index of sperm nuclei was 95%. This patient and his spouse did not choose assisted reproduction. For case 3, reproductive hormones, peripheral blood chromosomes and AZF were normal and the aneuploid rate of sperm chromosomes was 0.2%. The wife of this patient gave birth to a healthy baby after ova removal, fertilization and transplantation. For the control group, the aneuploid rate of sperm chromosomes and DNA damage index of sperm nuclei were approximately 0.3 and 30%, respectively. To sum up, sperm ultrastructure of infertile patients suffering from unusual sperm morphology is associated with DNA damage to some extent and can cause infertility. However, pregnancy is still possible through intracytoplasmic sperm injection. PMID- 26681048 TI - Study of genetic variation of eggplant cultivars by using RAPD-PCR molecular markers and the relationship with Phomopsis blight disease reaction. AB - Disease susceptibility and genetic variability in 10 eggplant genotypes were studied after inoculating Phomopsis vexans under confined field conditions. Random amplified polymorphic DNA (RAPD) markers were used to assess genetic variation and relationships among eggplant genotypes. The disease index of leaves ranged 0.208-13.79%, while fruit infection ranged 2.15-42.76%. Two varieties, Dohazari G and Laffa S, were found to be susceptible, 6 were moderately resistant, 1 was moderately susceptible, and BAU Begun-1 was resistant to P. vexans. Amplification of genomic DNA by using 3 RAPD primers produced 20 bands: 14 (70%) were polymorphic and 6 (30%) were monomorphic. The highest intra-variety similarity indices values were found in ISD 006, Ishurdi L, Jessore L, and BAU Begun-1 (100%), while the lowest was in Dohazari G (90%). The lowest genetic distance (0.0513) and the highest genetic identity (0.9500) were observed between the ISD 006 and Ishurdi L combinations. A comparatively higher genetic distance (0.3724) and the lowest genetic identity (0.6891) were observed between the ISD 006 and Dohazari G combinations. A dendogram was constructed based on Nei's genetic distance, which produced 2 main clusters of the genotypes - Cluster I: ISD 006, Ishurdi L, Marich begun L, BAU Begun-1, Marich begun S, and Chega and Cluster 2: Laffa S, Dohazari G, Jessore L, and Singhnath. Genetic variation and its relationship with disease susceptibility were assessed using RAPD markers, to develop disease-resistant varieties and improve eggplant crops. PMID- 26681049 TI - Effect of temperature on endogenous hormone levels and opposite phyllotaxy in maize leaf primordial. AB - Newly identified maize (Zea mays) mutants with opposite leaf phyllotaxy are important in the study of the maize crop. Previous studies have revealed the developmental mechanism of opposite phyllotaxy on the physiological, cellular, and molecular levels. However, there have been few reports regarding the effects of changes in endogenous hormone levels in maize leaf primordia under different conditions. We conducted field studies to examine the influence of different environmental factors on leaf primordia differentiation. Our results indicated that compared with other major environmental factors, temperature was significantly positively correlated with the ratio of maize plants with opposite phyllotaxy. We examined endogenous hormone levels in maize at different temperatures using an enzyme-linked immunosorbent assay. The results showed that the ratio of maize plants with opposite phyllotaxy was mainly influenced by the cytokinin/auxin ratio. In addition, at the same temperature, the ratio of cytokinin/auxin in maize with opposite phyllotaxy was significantly higher than that near isogenic lines with alternate phyllotaxy. PMID- 26681050 TI - Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia. AB - Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML. PMID- 26681051 TI - R337H mutation of the TP53 gene as a clinical marker in cancer patients: a systematic review of literature. AB - The germline R337H mutation of the TP53 gene has been associated with the development of many tumor types. This systematic review of literature investigated the association between the R337H mutation and the patients' family history and its predictive and prognostic value in cancer. Data were collected from articles archived in the PubMed, LILACS, MEDLINE, IBECS, and SciELO databases. The systematic review of literature was performed on 12 selected articles, describing a total of 175,462 individuals tested for the R337H mutation, including 1548 individuals with cancer and 118 individuals with a family history of Li-Fraumeni and Li-Fraumeni-like syndrome. Eight studies showed an association between the mutation and a family history of cancer in 411 patients, including 390 cases of cancer among family members. Patients with the homozygous mutant genotype experienced cancer recurrence, progressive disease, secondary cancer, and a short survival rate. Heterozygous patients showed a better response to treatment and increased survival rates than did patients with the homozygous mutant genotype from newborns to adult patients. In conclusion, the R337H mutation has significant predictive and prognostic value and is associated with tumorigenesis of the adrenal cortex. PMID- 26681052 TI - Lactic acid bacteria protect human intestinal epithelial cells from Staphylococcus aureus and Pseudomonas aeruginosa infections. AB - Staphylococcus aureus and Pseudomonas aeruginosa are opportunistic pathogens that cause nosocomial and food-borne infections. They promote intestinal diseases. Gastrointestinal colonization by S. aureus and P. aeruginosa has rarely been researched. These organisms spread to extra gastrointestinal niches, resulting in increasingly progressive infections. Lactic acid bacteria are Gram-positive bacteria that produce lactic acid as the major end-product of carbohydrate fermentation. These bacteria inhibit pathogen colonization and modulate the host immune response. This study aimed to investigate the effects of Lactobacillus acidophilus and Lactobacillus rhamnosus on enteric infections caused by the paradigmatic human pathogens S. aureus ATCC25923 and P. aeruginosa ATCC27853. The effect of whole cells and neutralized cell-free supernatant (CFS) of the lactobacilli on LoVo human carcinoma enterocyte (ATCC CCL-229) infection was analyzed by co-exposure, pre-exposure, and post-exposure studies. Simultaneous application of whole cells and CFS of the lactobacilli significantly eradicated enterocyte infection (P < 0.05); however, this effect was not seen when the whole cells and CFS were added after or prior to the infection (P > 0.05). This result could be attributed to interference by extracellular polymeric substances and cell surface hydrophobicity, which resulted in the development of a pathogen that did not form colonies. Furthermore, results of the plate count and LIVE/ DEAD BacLight bacterial viability staining attributed this inhibition to a non bacteriocin-like substance, which acted independently of organic acid and H2O2 production. Based on these results, the cell-free supernatant derived from lactobacilli was concluded to restrain the development of S. aureus and P. aeruginosa enteric infections. PMID- 26681053 TI - Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis. AB - Cervical cancer is associated with abnormal expression of multiple genes. Survivin and Bcl-2 proteins are apoptosis inhibitors. The tumor suppressor gene CD82, which encodes the protein KAI1, is downregulated in cervical cancer, and is associated with differentiation degree. We investigated the expression levels of three proteins and their correlation with metastasis in cervical cancer by comparing them in different cervical lesions. Immunohistochemistry was used to detect their three protein expression levels in the normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. The relationships between the protein expression levels and tumor type, clinical stage, tissue differentiation, invasion, and metastasis were analyzed. Survivin and Bcl-2 expression levels in cervical cancer were significantly higher than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). KAI1 expression was markedly lower in cervical cancer than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). There was no statistical difference between the expression levels of the three proteins in CIN and chronic cervicitis, but there were differences in expression between CIN and normal cervical tissues (P < 0.05). Bcl-2 and survivin levels were positively correlated while KAI1 expression was negatively correlated with clinical stage. Survivin and KAI1 expression levels were associated with lymph node metastasis (P < 0.05), and KAI1 expression was positively related with differentiation degree (P < 0.05). Survivin, Bcl-2, and KAI1 are metastasis-related factors in cervical cancer. Overexpression of survivin and Bcl-2, and low expression of KAI1 promotes cervical cancer progress and metastasis. PMID- 26681054 TI - Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis. AB - Cumulated evidence indicates that matrix metalloproteinase-3 (MMP-3) is significantly involved in cancer progression. Recent studies yielded conflicting results regarding the association between serum MMP-3 and ankylosing spondylitis (AS). To clarify this correlation, we performed a meta-analysis. Potential relevant studies were identified by searching the following databases: PubMed, Embase, CINAHL, Science Citation Index database, the Cochrane Library, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Data from eligible studies were extracted and included into the meta analysis using a random-effect model. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to assess the association between serum MMP-3 levels and AS. Thirteen case-control studies, including 707 AS cases and 442 healthy controls, were selected for the meta-analysis. The results indicate a significantly higher serum MMP-3 level in patients with AS than that in the controls (cases vs controls: SMD = 1.31, 95%CI = 0.84-1.78, P < 0.001). Ethnicity subgroup analysis indicated a higher MMP-3 level in Asian and Caucasian patients with AS (all P < 0.05). This meta-analysis indicates that increased serum MMP-3 level correlates with the development of AS, suggesting that MMP-3 may present a clinical value in reflecting the progression of AS. Further larger sample size studies are warranted. PMID- 26681055 TI - Angiotensin-converting enzyme gene polymorphism (insertion/deletion) and liver fibrosis in Turkish patients from the western Black Sea region, Turkey. AB - Chronic viral hepatitis B, chronic viral hepatitis C, non-alcoholic steatohepatitis, alcoholic liver disease, autoimmune hepatitis, primary biliary cirrhosis, and secondary biliary cirrhosis are important health issues worldwide. While an association between angiotensin-converting enzyme gene insertion/deletion (ACE gene I/D) polymorphism and liver fibrosis has been demonstrated in rat studies, the results of clinical studies area have been contradictory. The aim of this study was to assess the possible association between ACE gene I/D polymorphism and liver fibrosis in a large group of Turkish patients from the western Black Sea region. In 418 patients with different etiologies, ACE gene I/D polymorphism and serum ACE levels were investigated. The distribution of the "DD", "ID", "II" genotypes of the ACE gene were 32.5, 48.8, and 18.7% in the mild to moderate fibrosis group (N = 246, F:1-3 according to Ishak's score) and 39.0, 44.2, and 16.9% in the advanced fibrosis group (N = 172, F:4-6 according to Ishak's score). A significant correlation between serum ACE levels and ACE gene alleles was identified (P < 0.001): serum ACE levels of patients with D alleles were higher than those of patients with I alleles [44 (min 7-max 101) versus 29 (min 7-max 96)]. Patients with advanced fibrosis were also found to be older than those with mild to moderate fibrosis (P < 0.001). No significant association was noted between the patient gender and fibrosis severity. We conclude that ACE I/D polymorphism is not associated with the degree of liver fibrosis. PMID- 26681056 TI - Regulating effect of MMP-9 and TIMP-1 in pituitary adenoma invasion. AB - Pituitary adenomas can cause endocrine disorder and organ damage, with some aggressive ones leading to a high postoperative recurrence rate. The occurrence and development of these type of tumors is closely related with matrix metalloproteinases (MMPs) and endogenous specific tissue inhibitor of MMPs (TIMPs). In this study, the relationship between pituitary adenoma invasion and the changes in MMP-8 and TIMP-1 expressions is analyzed. Specimens from sixty patients with pituitary adenoma were collected in our hospital after surgery, including thirty cases of invasive pituitary adenomas and thirty cases of noninvasive pituitary adenomas. Western blotting and real-time PCR were used to detect MMP-8/TIMP-1 protein and mRNA levels, respectively, in the two types of pituitary adenomas, while ELISA was used to detect both compounds' levels in the patient's serum. Compared with noninvasive pituitary adenomas, MMP-8 was significantly overexpressed in invasive pituitary adenomas, while TIMP-1 was obviously lower (P < 0.05 for both). Moreover, MMP-8 mRNA expression in invasive pituitary adenomas was significantly higher than in noninvasive pituitary adenomas, while TIMP-1 mRNA expression was markedly lower (P < 0.05 for both). Finally, MMP-8 expression in the serum is upregulated in patients with invasive pituitary adenomas relative to the noninvasive ones, and the expression of TIMP-1 significantly reduced (P < 0.05 for both). These results show that increased MMP 8 and decreased TIMP-1 expressions are closely related to the invasive pituitary adenoma, and can be helpful for the evaluation. PMID- 26681057 TI - Expression of Magnaporthe oryzae genes encoding cysteine-rich proteins secreted during nitrogen starvation and interaction with its host, Oryza sativa. AB - Previous studies have shown that the blast fungus, Magnaporthe oryzae, may experience nitrogen starvation during infection of its plant host (rice,Oryza sativa). Here, we studied the expression of seven genes encoding cysteine-rich proteins with N-terminal signal peptides during nitrogen limitation and throughout the infection process. Some genes were upregulated to a greater extent in weak pathogenic strains than in strong pathogenic strains when they were cultured in complete media, and the expression of some genes was higher in both weak and strong pathogenic strains cultured in 1/10-N and nitrogen starvation media. Furthermore, the expression of these genes was upregulated to different extents in the early stages of M. oryzae infection. These data demonstrate that the genes of interest are highly expressed in weak and strong pathogenic strains cultured under nitrogen limitation and at the early stage of the infection process. This indicates that cysteine-rich secreted proteins in the blast fungus might be involved in establishing disease in the host and that they are sensitive to nitrogen levels. Thus, their role in sensing nitrogen availability within the host is implied, which provides a basis for further functional identification of these genes and their products during plant infection. PMID- 26681058 TI - Genetic diversity in mutated and non-mutated rice varieties. AB - We studied the genetic variability due to mutation induced by gamma-rays (10, 15, and 20 Kr) on various traits of twelve rice genotypes. Mutated and non-mutated seeds were sown in the field between July 2013 and 2014 using a split plot design. Yield and yield-related trait data was recorded, which showed significant (P < 0.05) genotypic and irradiation effects. Gamma radiation exerted non significant effects on the panicle length of all plants, indicating the uniformity of performance of this character at different radiation levels. The plant height, grains per main panicle, panicle length, 1000-grain weight, grain weight per main panicle, and fertility percentage was minimum in Basmati-198, Basmati-Pak, Shaheen-2000, Super Basmati, Basmati-385, and Super Basmati, respectively, when exposed to radiation at 20 Kr. However, Basmati-370 attained maximum flag leaf area at this level of radiation. Broad sense heritability ranged from 72.0 to 97.7%, indicating the possibility of selection during earlier generations. Phenotypic correlation was positive and significant between grain weight per main panicle with panicle length and flag leaf area. Number of grains per main panicle and genotypic correlation were positive among grain weight per main panicle, panicle length, fertility percentage, 1000-grain weight, and plant height, indicating the effectiveness of these traits in the selection for yield. Phylogenetic analyses revealed a pair-wise similarity ranging from 0.51-0.76 before mutation and 0.39-0.89 after mutation. This study proved that gamma-rays at 20 Kr would be most effective in creating genetic variability in the existing germplasm. PMID- 26681059 TI - Cloning and functional analysis of goat SWEET1. AB - SWEETs are a recently discovered class of sugar transporters that mediate glucose uptake in the intestine and mammary glands. Our objectives were to clone goat SWEET1 and conduct a functional analysis of its effect on glucose efflux in goat mammary gland epithelial cells. We cloned and sequenced the goat SWEET1 gene from goat mammary glands, then conducted an analysis of the structure of goat SWEET1, including a prediction of the transmembrane helices and potential N-glycosylation sites. To investigate the biological function of goat SWEET1, we also generated goat SWEET1-transfected goat mammary gland epithelial cells using the eukaryotic expression vector pcDNA3.1-gSWEET1. Goat SWEET1 overexpression can reduce glucose absorption in mammary gland epithelial cells with increasing expression of GLUT1, GLUT4, and GLUT12, which may be attributed to glucose efflux arising from the leading role played by goat SWEET1. This study will improve our understanding of the glucose balance in mammary glands and the level of glucose in milk. PMID- 26681060 TI - Downregulation of MACC1 expression enhances cisplatin sensitivity in SKOV-3/DDP cells. AB - The aim of this study was to investigate the correlation between MACC1 expression and resistance to cisplatin (DDP) in DDP-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP). MACC1 mRNA and protein expression levels in SKOV-3 and SKOV-3/DDP cells were detected by reverse transcriptase polymerase chain reaction and western blot. The SKOV-3/DDP cells were divided into 5 groups: control, shVect (transfected with p-super-EGFP-1 plasmid), pshMACC1 (transfected with psuper-EGFP-shMACC1 plasmid), PD (pretreated with 20 MUM PD98059), and combined (transfected with psuper-EGFP-shMACC1 plasmid and pretreated with 20 MUM PD98059) groups. Cisplatin sensitivity and cell apoptosis in SKOV-3/DDP cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. ERK1/2 and p-ERK1/2 expression was determined by western blot. MACC1 mRNA and protein expression levels in SKOV-3/DDP cells were 2.66 +/- 0.54 and 1.95 +/- 0.45 times those seen in SKOV-3 cells (P < 0.05). Cisplatin sensitivity of pshMACC1 group was much higher than that in the control and shVect groups. Cisplatin-induced cell apoptosis rates increased significantly in the pshMACC1, PD, and combined groups, compared to the control and shVect groups. Moreover, the apoptosis rate was the highest in the combined group among the 5 groups (IC50 = 20.836 +/- 0.629 MUM). p-ERK1/2 expression decreased significantly in the pshMACC1, PD, and combined groups (this decrease was the most obvious in the combined group). In conclusion, downregulation of MACC1 expression could enhance cisplatin sensitivity and decrease drug resistance in SKOV- 3/DDP cells. PMID- 26681061 TI - Effect of siRNA targeting HER2/neu on the proliferation and viability of prostate cancer PC-3M cells. AB - The aim of this study was to investigate the effect of a small interfering RNA (siRNA) targeting human epidermal growth factor receptor 2 (HER2/neu) on the proliferation and viability of prostate cancer PC-3M cells. Chemically synthesized siRNA targeting HER2/neu was transfected into PC-3M cells by using liposomes, and cells transfected with empty liposomes, a negative siRNA sequence, or nothing (untransfected) were used as controls. mRNA and protein levels of HER2/neu were detected using reverse transcription-polymerase chain reaction and western blot, respectively. The inhibitory action of HER2/neu siRNA on the in vitro growth of PC-3M cells was assessed by the cholecystokinin 8 assay and apoptosis was detected using flow cytometry. Cells transfected with HER2/neu siRNA showed decreased mRNA and protein levels of HER2/neu compared to control groups (P < 0.05). The survival rate of PC-3M cells decreased significantly after transfection with HER2/neu siRNA compared to that of untransfected cells (55.39 +/- 1.60 and 81.42 +/- 0.80%, respectively; P < 0.05). The apoptosis rate in cells transfected with HER2/neu siRNA was quite high (45.60 +/- 0.70%) compared to that of blank control, empty liposome, and negative siRNA sequence groups (P < 0.05). In conclusion, siRNA targeting HER2/neu inhibits HER2/neu expression in PC 3M cells, resulting in an inhibition in proliferation and an induction of apoptosis. PMID- 26681062 TI - Isolation and characterization of microsatellite markers for Osmanthus fragrans (Oleaceae) using 454 sequencing technology. AB - Osmanthus fragrans (Oleaceae) is an evergreen shrub or small tree that grows in south China. In this study, Roche 454 FLX+ sequencing combined with the magnetic bead enrichment method was used to isolate microsatellite markers from the genome of O. fragrans. A total of 1471 microsatellites that contained enough flanking sequences for primer pair design were identified from 89,633 raw sequencing reads. One hundred primer pairs were randomly chosen to test primer amplification efficiency. Among these tested primer pairs, 20 yielded polymorphic amplification products across 16 individuals from the Albus, Luteus, and Aurantiacus groups. The number of alleles ranged from 2 to 6, with an average of 3.7. The observed heterozygosity ranged from 0 to 0.813, with an average of 0.460. Shannon's information index ranged from 0.463 to 1.707, with an average of 0.975. Six loci (Of 05, Of 06, Of 08, Of 12, Of 15, and Of 19) deviated significantly from Hardy Weinberg equilibrium (P < 0.05), which was due to an excess of homozygotes or heterozygotes. Nine pairs of loci (Of 01 and Of 05; Of 04 and Of 05; Of 01 and Of 06; Of 04 and Of 12; Of 02 and Of 13; Of 04 and Of 13; Of 12 and Of 13; Of 04 and Of 19; Of 05 and Of 19) showed significant linkage disequilibrium, which indicated significant allelic association between the loci. This set of microsatellite markers will be valuable for molecular marker-assisted breeding in O. fragrans. PMID- 26681063 TI - Population genetic structure of Myzus persicae nicotianae (Hemiptera: Aphididae) in China by microsatellite analysis. AB - The tobacco aphid, Myzus persicae nicotianae (Hemiptera: Aphididae), is an important agricultural pest that feeds on host plants and transmits plant viruses in China. To effectively control this pest, we investigated the genetic variation and genetic structure of 54 populations of tobacco aphids collected in China, using five microsatellite loci. An average of 7 alleles with effective number ranging from 1.5 to 6.6 was detected using these five loci, and the average polymorphic information content (PIC) was 0.652, suggesting that the five selected microsatellite loci were polymorphic and suitable for the study of population genetics. The expected heterozygosities in the populations studied ranged from 0.128 and 0.653, with an average value of 0.464. However, the observed heterozygosities ranged from 0.250 and 0.942 (average = 0.735), revealing a high genetic variability and heterozygosity excess in the Chinese tobacco aphid populations. The global fixation index (F(ST)) and mean gene flow (N(m)) were 0.34 (P < 0.0001) and 0.50, respectively, suggesting the high genetic differentiation among Chinese populations. The 54 populations of tobacco aphids were classified into two groups. The populations did not cluster geographically, as populations from the same provinces were usually present in different clusters. This was also confirmed by the Mantel test, which showed no significant correlation between the genetic distance and geographical distance or altitude. Long distance migration might be responsible for the lack of distance-related isolation. PMID- 26681064 TI - A SCAR marker for the analysis of chloroplast DNA from different cultivars of Cornus officinalis. AB - The aims of this study were to establish a random amplified polymorphic DNA (RAPD) fingerprint database of chloroplast DNA (cpDNA) from different cultivars of Cornus officinalis and to convert RAPD markers to sequence characterized amplified regions (SCAR) markers. A method of extraction was established that was suitable for obtaining cpDNA from samples rapidly dried in silicone; an RAPD fingerprint database was built; and the genetic distance between samples was used as statistical clustering variables for calculating DICE genetic similarity coefficients and for building a kinship tree chart. RAPD markers were converted to SCAR markers to design specific primers, and samples from C. officinalis cultivars, plants of the same family, and its adulterants, were used for amplification and identification. Fifteen amplified primers with stable polymorphisms were screened for amplification of 130 copies of materials. In total, 57 sites were achieved, 40 of which were polymorphic, and the polymorphic rate was up to 70.18%. A genetic tree was built based on seven cultivars. SCAR markers of C. officinalis cpDNA were successfully converted into RAPD markers. cpDNA samples from hawthorn, C. officinalis, Cornus wood, and grape were used for SCAR amplification, and their bands were distinctly different. In conclusion, SCAR markers and cpDNA may be used for research on C. officinalis and its adulterants, and the results may provide a basis for identifying germplasm and screening fine varieties at a molecular level. PMID- 26681066 TI - Alcohol industry and governmental revenue from young Australians. AB - Objective The aim of the present study was to estimate the revenues collected by government and industry from alcohol consumption by young Australians in 2010. Methods Statistical analyses were performed on data from the Australian National Drug Strategy Household Survey 2010 and alcohol data collected from an online retailer to calculate the proportion, frequency, quantity and revenues from alcohol consumption by young Australians. Results One-third of adolescents (12-17 years old) and 85% of young adults (18-25 years old) consume alcohol. More than half the adolescents' alcohol consumption is from ready-to-drink spirits. Revenue generated from alcohol consumption by 12-25 year olds is estimated at $4.8 billion in 2010 (2014 Australian dollars): $2.8 billion to industry (sales) and $2.0 billion to government (taxes). Conclusions Alcohol consumption by young Australians is prevalent, and young Australian drinkers consume alcohol in substantial amounts. The industry and taxation revenue from young drinkers is also considerable. It would be in the public interest to divert some of this revenue towards health initiatives to reduce drinking by young people, especially given the high societal costs of alcohol consumption. What is known about the topic? Australian adolescents aged 12-17 years consume substantial amounts of alcohol, and substantial amounts of revenue are generated from alcohol sales to them. What does this paper add? This paper provides recent estimates of alcohol consumption and revenue generated by Australian adolescents, and extends estimates to young adults aged 18-25 years. What are the implications for practitioners? A substantial proportion of Australian young people consume alcohol. The sales and taxation revenue generated from young people's drinking is substantial at A$4.8 billion in 2010 and is higher in real terms than estimates from previous studies. Some of the alcohol taxation revenue could be diverted to health promotion and education for young people, because the costs of alcohol consumption in terms of health outcomes and productivity losses for these age groups are expected to be especially high. PMID- 26681065 TI - Are bidirectional associations of obesity and depression already apparent in childhood and adolescence as based on high-quality studies? A systematic review. AB - Our aim was to evaluate bidirectional associations of obesity and depression in cross-sectional and longitudinal studies with initial assessments in childhood or adolescence. The clarification of these relationships may support the development of innovative interventions, e.g. based on nutrition and mental health. A systematic literature search was conducted in MEDLINE. Main inclusion criteria were (i) assessment of subjects <18 years at baseline, (ii) use of validated psychometric instruments and (iii) elicitation of objectively measured anthropometric data at least at one time point. Twenty-four studies met our inclusion criteria. Out of 19, 14 cross-sectional studies confirmed a significant association of obesity and depression. Three out of eight longitudinal studies reported associations between obesity and subsequent depression in female children and adolescents only, and three out of nine studies obtained evidence in favour of the other direction with two studies revealing significant results only for female and one only for male children and adolescents. Evidence is mixed, and secure conclusions are hampered by the methodological variance of the included studies. Relationships are seemingly more readily detectable in female children adolescents and in the cross-sectional compared with the longitudinal analyses. Possibly, the joint development of obesity and depression in predisposed subjects accounts for the latter discrepancy. PMID- 26681067 TI - Baicalin Reverses Depressive-Like Behaviours and Regulates Apoptotic Signalling Induced by Olfactory Bulbectomy. AB - Apoptosis is thought to be involved in neurological disorders including major depression. In this study, we examined whether the polyphenolic compound baicalin could decrease apoptosis in the olfactory bulbectomy (OBX) depression rat model. OBX rats exhibited decreased performance in depression-like behavioural tests and showed evidence of increased oxidative stress, decreased synaptophysin expression, and hippocampal apoptosis. Treatment with baicalin (20 and 40 mg/kg) significantly reversed all of these changes. Baicalin modulated the levels or activity of malondialdehyde, superoxide dismutase, and glutathione peroxidase and prevented apoptotic protease-activating factor-1 expression, effectively suppressing caspase-mediated apoptosis signalling cascades. Our results demonstrate that baicalin has potent antidepressant activity, likely because of its ability to suppress apoptosis. PMID- 26681069 TI - Location and functional characterization of the right atrioventricular pacemaker ring in the adult avian heart. AB - Previous histological studies showed that in addition to a sinus node, an atrioventricular (AV) node, an AV bundle, left and right bundle branches, birds also possess a right AV-Purkinje ring that is located in the atrial sheet of the right muscular AV-valve along all its base length. The functionality of the AV Purkinje ring is unknown. In this work, we studied the topology of pacemaker myocytes in the atrial side of the isolated chicken spontaneously contracting right muscular AV-valve using the method of microelectrode mapping of action potentials. We show that AV-cells having the ability to show pacemaking reside in the right muscular AV-valve. Pacemaker action potentials were exclusively recorded close to the base of the valve along its whole length from dorsal to the ventral attachment to the interventricular septum. These action potentials have much slower rate of depolarization, lower amplitude, and higher diastolic depolarization than action potentials of Purkinje (conducting) cells. We conclude the right AV-valve has a ring bundle of pacemaker cells (but not Purkinje cells) in the adult chicken heart. PMID- 26681068 TI - Neuropeptide Y in noradrenergic neurons induces obesity in transgenic mouse models. AB - Neuropeptide Y (NPY) in noradrenergic neurons plays an important role in modulating the release and effects of catecholamines in a prolonged stress response. Among other functions, it controls energy metabolism. Transgenic expression of Npy in noradrenergic neurons in mice allowed showing that it is critical for diet- and stress-induced gain in fat mass. When overexpressed, NPY in noradrenergic neurons increases adiposity in gene-dose-dependent fashion, and leads to metabolic disorders such as impaired glucose tolerance. However, the mechanisms of obesity seem to be different in mice heterozygous and homozygous for the Npy transgene. While in heterozygous mice the adipogenic effect of NPY is important, in homozygous mice inhibition of sympathetic tone leading to decreased lipolytic activity and impaired brown fat function, as well as increased endocannabinoid levels contribute to obesity. The mouse model provides novel insight to the mechanisms of human diseases with increased NPY due to chronic stress or gain-of-function gene variants, and a tool for development of novel therapeutics. PMID- 26681070 TI - Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties. AB - We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 MU/mL) and lower hemolytic activity (80.2 MUg/mL for 3a versus 19.7 MUg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection. PMID- 26681071 TI - Patient quality of life following induction of oral immunotherapy for food allergy. AB - BACKGROUND: Patient quality of life improves following successful completion of oral immunotherapy (OIT), but the process itself might have undesirable effects. We aimed to evaluate patient quality of life following OIT initial induction. METHODS: The Hebrew version of the Food Allergy Quality of Life Questionnaire Parental Form (FAQLQ-PF) was validated and administered to the parents of children following the first week of OIT for food allergy (n = 119). Patient demographics and clinical history as well as the course of initial induction week were reviewed. RESULTS: Pre-OIT severity of food allergy, defined as severity of reactions due to accidental exposure to the allergenic food (anaphylactic reactions, p = 0.017; epinephrine use, p = 0.049; emergency room referrals p = 0.003; and hospital admissions, p = 0.015) and a lower number of tolerated doses during initial induction, reflective of a lower maximal tolerated dose for the different allergens (p = 0.011) were associated with worse total FAQLQ-PF scores. The number of tolerated doses during induction and pre-OIT emergency room referrals remained significantly associated with worse total score of the FAQLQ PF on multivariate analysis (p = 0.016 and p = 0.005, respectively). The correlation between the number of tolerated doses and quality of life scores was moderate-strong primarily in children aged 6-12 years (Total score, r = -0.41, p = 0.001; Emotional Impact r = -0.42, p = 0.001; Food Anxiety, r = -0.38, p = 0.002; Social and Dietary Limitations, r = -0.33, p = 0.009). CONCLUSIONS: Pre OIT reaction severity affects quality of life in both preschool and school-aged food-allergic children. In contrast, a lower maximal tolerated dose during OIT induction is associated with worse indices of quality of life primarily in children aged 6-12 years. PMID- 26681072 TI - A simple route to diverse noble metal-decorated iron oxide nanoparticles for catalysis. AB - Developing facile synthetic routes to multifunctional nanoparticles combining the magnetic properties of iron oxides with the optical and catalytic utility of noble metal particles remains an important goal in realizing the potential of hybrid nanomaterials. To this end, we have developed a single route to noble metal-decorated magnetic nanoparticles (Fe3O4@SiO2-M; M = Au, Pd, Ag, and PtAg) and characterized them by HRTEM and STEM/EDX imaging to reveal their nanometer size (16 nm Fe3O4 and 1-5 nm M seeds) and uniformity. This represents one of the few examples of genuine multifunctional particles on the nanoscale. We show that these hybrid structures have excellent catalytic activity for the reduction of 4 nitrophenol (knorm = 2 * 10(7) s(-1) mol(Pd)(-1); 5 * 10(6) s(-1) mol(Au)(-1); 5 * 10(5) s(-1) mol(PtAg)(-1); 7 * 10(5) s(-1) mol(Ag)(-1)). These rates are the highest reported for nano-sized comparables, and are competitive with mesoparticles of similar composition. Due to their magnetic response, the particles are also suitable for magnetic recovery and maintain >99% conversion for at least four cycles. Using this synthetic route, Fe3O4@SiO2-M particles show great promise for further development as a precursor to complicated anisotropic materials or for applications ranging from nanocatalysis to biomedical sensing. PMID- 26681073 TI - On the pharmacology of oxidative burst of human neutrophils. AB - The effect of three therapeutically used drugs and five polyphenolic compounds on the mechanism of oxidative burst was compared in whole blood and isolated neutrophils at cellular and molecular level. In 10 microM concentration, the compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin (N-f-5HT) > curcumin (CUR) > quercetin (QUER) > arbutin (ARB) > resveratrol (RES) > dithiaden (DIT) > carvedilol (CARV) > brompheniramine (BPA). The ratio between the percentage inhibition of extracellular versus intracellular chemiluminescence (CL) followed the rank order QUER > N-f-5HT > RES > CUR > DIT and is indicative of the positive effect of the compounds tested against oxidative burst of neutrophils, demonstrating suppression of reactive oxygen species extracellularly with minimal alteration of intracellular reactive oxygen species (ROS). Activation of protein kinase C was significantly decreased by DIT, CUR, QUER and N-f-5HT. CARV, DIT, QUER and ARB reduced activated neutrophil myeloperoxidase release more significantly compared with the effect on superoxide anion generation. All compounds tested increased the activity of caspase-3 in cell-free system. It is suggested that other regulatory mechanisms than protein kinase C might participate in the inhibition of neutrophil activation with the compounds tested. Different mechanisms are concerned in controlling the assembly of NADPH oxidase and the regulatory role of calcium ions is suggested. Compounds decreasing the amount of extracellular ROS generation, yet affecting but minimally intracellular ROS generation, are promising for further investigation in vivo. PMID- 26681074 TI - Can bioactive compounds of Crocus sativus L. influence the metabolic activity of selected CYP enzymes in the rat? AB - Safranal and crocin are biologically active compounds isolated from Crocus sativus L., commonly known as saffron. Clinical trials confirm that saffron has antidepressant effect, thus being a potential valuable alternative in the treatment of depression. The aim of the present study was to determine, whether systemic administration of safranal and crocin can influence the metabolic activity of CYP3A, CYP2C11, CYP2B, and CYP2A in rat liver microsomes (RLM). The experiments were carried out on male Wistar albino rats intragastrically administered with safranal (4, 20, and 100 mg/kg/day) or with intraperitoneal injections of crocin (4, 20, and 100 mg/kg/day). Our results demonstrate the ability of safranal and crocin to increase the total protein content and to change the metabolic activity of several CYP enzymes assessed as CYP specific hydroxylations of testosterone in RLM. Crocin significantly decreased the metabolic activity of all selected CYP enzymes, while safranal significantly increased the metabolic activity of CYP2B, CYP2C11 and CYP3A enzymes. Therefore, both substances could increase the risk of interactions with co-administered substances metabolized by cytochrome P450 enzymes. PMID- 26681075 TI - Hyperbilirubinemia decreases physiological markers in adjuvant-induced arthritis. AB - There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact. PMID- 26681076 TI - Boldine attenuates cholestasis associated with nonalcoholic fatty liver disease in hereditary hypertriglyceridemic rats fed by high-sucrose diet. AB - The aim of the current study was to clarify the effect of high sucrose diet (HSD) on bile formation (BF) in rats with hereditary hypertriglyceridemia (HHTg). Potentially positive effects were studied for boldine, a natural choleretic agent. Administration of HSD to HHTg rats led to increased triglyceride deposition in the liver. HSD reduced BF as a consequence of decreased biliary secretion of bile acids (BA) and glutathione. Responsible mechanism was down regulation of hepatic transporters for BA and glutathione, Bsep and Mrp2, respectively. Moreover, gene expressions of transporters for other constituents of bile, namely Abcg5/8 for cholesterol, Abcb4 for phospholipids, and Oatp1a4 for xenobiotics, were also reduced by HSD. Boldine partially attenuated cholestatic effect of HSD by promotion of biliary secretion of BA through up-regulation of Bsep and Ntcp, and by increase in biliary secretion of glutathione as a consequence of its increased hepatic disposition. This study demonstrates mechanisms of impaired BF during nonalcoholic fatty liver disease induced by HSD. Altered function of responsible transporters suggests also potential for changes in kinetics of drugs, which may complicate pharmacotherapy in subjects with high intake of sucrose, and with fatty liver disease. Sucrose induced alterations in BF may be alleviated by administration of boldine. PMID- 26681077 TI - Sirtuin 1 modulation in rat model of acetaminophen-induced hepatotoxicity. AB - Sirtuin 1 (SIRT1) is involved in important biological processes such as energy metabolism and regulatory functions of the cell cycle, apoptosis, and inflammation. Our previous studies have shown hepatoprotective effect of polyphenolic compound resveratrol, which is also an activator of SIRT1. Therefore, the aim of our present study was to clarify the role of SIRT1 in process of hepatoprotection in animal model of drug-induced liver damage. Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by single dose of acetaminophen (APAP). Some rats and hepatocytes were treated by resveratrol or synthetic selective activator of sirtuin 1 (CAY10591). The degree of hepatotoxicity, the activity and expression of the SIRT1 were determined by biochemical, histological and molecular-biological assessments of gained samples (plasma, liver tissue, culture media and hepatocytes). Resveratrol and CAY attenuated APAP-induced hepatotoxicity in vivo and in vitro. Moreover, both drugs enhanced APAP-reduced SIRT1 activity. Our results show that modulation of the SIRT1 activity plays a role in hepatoprotection. Synthetic activators of SIRT1 would help in understanding the role of SIRT1 and are therefore a major boost towards the search for specific treatment of liver disease. PMID- 26681078 TI - Inhibition of oxidative stress in brain during rat adjuvant arthritis by carnosine, trolox and novel trolox-carnosine. AB - Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP 1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain. PMID- 26681079 TI - Effect of sulodexide on vascular responses and liver mitochondrial function in diabetic rats. AB - This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg(-1). SLX was administered i.p., at dose 100 IU.kg( 1) daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO(2)(S(3))], [QO(2)(S(4))] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function. PMID- 26681080 TI - Positive effects of different drug forms of silybin in the treatment of metabolic syndrome. AB - Silymarin and silybin are widely used for their hepatoprotective properties. Our previous studies confirm positive effect of silymarin on lipoprotein profile and lipid homeostasis. Advanced drug forms may improve the bioavailability of these compounds. In this study, we investigate the effects of silybin in different drug forms (standardized silybin, micronized silybin, and silybin in form of phytosomes) on dyslipidemia and glucose metabolism in hereditary hypertriglyceridemic (HHTg) rats. Male HHTg rats were divided into four groups of seven animals and were fed by experimental diets. Silybin significantly decreased serum level of triglycerides in groups of rats fed by standardized silybin and silybin in form of phytosomes compared to control group. Results show that silybin did not affect the total cholesterol level, but significantly increased the levels of HDL cholesterol in all groups of animals. Silybin in a standardized form had the highest hypotriglyceridemic effect. On the other hand, the micronized form has caused the highest increase of protective HDL and most significantly decreased glucose and insulin levels. Our results suggest that silybin is probably responsible for some positive properties of silymarin. Subsequent dose-dependent studies of silybin action may reveal the intensity of its positive effects on lipid and glucose parameters. PMID- 26681081 TI - Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns. AB - Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings. PMID- 26681082 TI - OPRM1 and ABCB1 polymorphisms and their effect on postoperative pain relief with piritramide. AB - Genetic factors may contribute to the differential response to opioids. The aim of this study was to evaluate the association between polymorphisms of u1-opioid receptor gene OPRM1 (rs1799971), and P-glycoprotein transporter gene ABCB1 (rs1045642, rs2032582), and piritramide efficacy under postoperative patient controlled analgesia (PCA). In 51 patients, OPRM1 variant was associated with decreased efficacy in early postoperative period evidenced by sum of pain intensity difference in the 0-6 h postoperative period (SPID(0-6)), (F=3.27, p=0.029). Mean (SD) SPID(0-6) was observed in the 118AA genotype 22.9 (6.1) mm, which was significantly higher from the 118GG genotype 10.0 (4.4) mm, p=0.006. The lowest cumulative dose was recorded in 118AA genotype 19.1 (9.8) mg, which was significantly less than in the 118GG genotype group 36.6 (6.1) mg, p=0.017. Opioid-induced adverse effects were observed in 11, 30, and 100 % of patients in 118AA, 118AG, and 118GG genotype groups, respectively (p<0.05). Piritramide efficacy and safety was not significantly affected by ABCB1 (rs1045642, rs2032582) polymorphisms. Variant OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide. Decreased efficacy leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects. PMID- 26681083 TI - Maternal and neonatal effects of remifentanil in women undergoing cesarean section in relation to ABCB1 and OPRM1 polymorphisms. AB - The aim of our study was to evaluate possible effect of ABCB1, and OPRM1 polymorphisms on the efficacy and safety of remifentanil in women undergoing elective cesarean section under general anesthesia. Women received remifentanil (1 microg/kg i.v.) 30 s prior to the induction to standardized general anesthesia. The ABCB1 (rs2032582, rs1045642) and OPRM1 (rs1799971) polymorphisms were analyzed from maternal peripheral blood. The basal hemodynamic and demographic parameters in the study population (n=54) were similar in all the subgroups. The median +/- SD increase of systolic blood pressure at 5 min from the baseline was practically completely abolished in homozygous carriers of ABCB1 variants in comparison with wild-type subjects -2.67+/-25.0 vs. 16.57+/-15.7 mm Hg, p<0.05 for rs2032582, and 2.00+/-23.9 vs. 22.13+/-16.8 mm Hg, p<0.05, for rs1045642, respectively. While no neonate belonging to ABCB1 wild-type homozygous or OPRM1 variant carrying mothers needed any resuscitative measure, 10.5 % of the neonates belonging to OPRM1 wild-type homozygous mothers received resuscitative support similarly as 11.1 %, and 12.5 % of neonates of mothers carrying variants of rs2032582, and rs1045642, respectively. Decreased stabilizing effects of remifentanil on maternal hemodynamics has been observed in ABCB1 wild type mothers, while the adaptation of the neonates was clinically worse in OPRM1 wild type, and ABCB1 variant allele carriers. PMID- 26681084 TI - Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer. AB - Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31 52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity. PMID- 26681085 TI - Whole exome sequencing analysis of ABCC8 and ABCD2 genes associating with clinical course of breast carcinoma. AB - The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance. PMID- 26681086 TI - The Course of Bone Marrow Edema in Early Undifferentiated Arthritis and Rheumatoid Arthritis: A Longitudinal Magnetic Resonance Imaging Study at Bone Level. AB - OBJECTIVE: In patients with rheumatoid arthritis (RA), bone marrow edema (BME) scores are associated with development of erosions. However, little is known about the course and outcome of BME at bone level. We undertook this study to determine the association of BME and synovitis with the development of erosions in the same bone longitudinally. METHODS: Using 1.5T magnetic resonance imaging at baseline and at 4- and 12-month follow-up, we studied 1,947 bones of the metacarpophalangeal, wrist, and metatarsophalangeal joints in 59 patients presenting with RA or undifferentiated arthritis. Scanning and scoring of BME, synovitis, and erosions were performed according to the Outcome Measures in Rheumatology Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. We evaluated the relationship of the course of BME and synovitis with erosive progression at bone level during 1 year. RESULTS: Of the bones showing BME at baseline (n = 203), BME persisted in 56%, disappeared in 39%, and disappeared and then reappeared in 5%. Stratified analyses at baseline revealed that BME was associated with erosive progression both in the presence and in the absence of local synovitis, with odds ratios (ORs) of 7.5 (95% confidence interval [95% CI] 3.8-14.9) and 6.9 (95% CI 1.9-25.6), respectively. However, local synovitis was not associated with erosive progression in the presence or in the absence of BME (ORs of 2.0 [95% CI 0.6-7.0] and 1.9 [95% CI 0.8-4.1], respectively). In multivariable generalized estimating equation analyses, persistent BME was strongly associated with erosive progression (OR 60.5 [95% CI 16.8-218.1]) in contrast to persistent synovitis (OR 1.3 [95% CI 0.4-4.4]). CONCLUSION: BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independently of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for comprehending the development of erosions in RA. PMID- 26681102 TI - A Novel beta-Globin Chain Hemoglobin Variant, Hb Allentown [beta137(H15)Val->Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly. AB - Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable beta-globin variant that we have named Hb Allentown [beta137(H15)Val->Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or beta6(A3)Glu->Val;beta132(H10)Lys->Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory. PMID- 26681103 TI - Engineering of Lanthanide-Doped Upconversion Nanoparticles for Optical Encoding. AB - Lanthanide-doped upconversion nanoparticles (UCNPs) are an emerging class of luminescent materials that emit UV or visible light under near infra-red (NIR) excitations, thereby possessing a large anti-Stokes shift property. Due to their sharp excitation and emission bands, excellent photo- and chemical stability, low autofluorescence, and high tissue penetration depth of the NIR light used for excitation, UCNPs have surpassed conventional fluorophores in many bioapplications. A better understanding of the mechanism of upconversion, as well as the development of better approaches to preparing UCNPs, have provided more opportunities to explore their use for optical encoding, which has the potential for applications in multiplex detection and imaging. With the current ability to precisely control the microstructure and properties of UCNPs to produce particles of tunable emission, excitation, luminescence lifetime, and size, various strategies for optical encoding based on UCNPs can now be developed. These optical properties of UCNPs (such as emission and excitation wavelengths, ratiometric intensity, luminescence lifetime, and multicolor patterns), and the strategies employed to engineer these properties for optical encoding of UCNPs through homogeneous ion doping, heterogeneous structure fabrication and microbead encapsulation are reviewed. The challenges and potential solutions faced by UCNP optical encoding are also discussed. PMID- 26681104 TI - Gas-generated thermal oxidation of a coordination cluster for an anion-doped mesoporous metal oxide. AB - Central in material design of metal oxides is the increase of surface area and control of intrinsic electronic and optical properties, because of potential applications for energy storage, photocatalysis and photovoltaics. Here, we disclose a facile method, inspired by geochemical process, which gives rise to mesoporous anion-doped metal oxides. As a model system, we demonstrate that simple calcination of a multinuclear coordination cluster results in synchronic chemical reactions: thermal oxidation of Ti8O10(4-aminobenzoate)12 and generation of gases including amino-group fragments. The gas generation during the thermal oxidation of Ti8O10(4-aminobenzoate)12 creates mesoporosity in TiO2. Concurrently, nitrogen atoms contained in the gases are doped into TiO2, thus leading to the formation of mesoporous N-doped TiO2. The mesoporous N-doped TiO2 can be easily synthesized by calcination of the multinuclear coordination cluster, but shows better photocatalytic activity than the one prepared by a conventional sol-gel method. Owing to an intrinsic designability of coordination compounds, this facile synthetic will be applicable to a wide range of metal oxides and anion dopants. PMID- 26681105 TI - [Telemedicine in thrombotic microangiopathies: A way forward in rare diseases requiring emergency care]. AB - Thrombotic microangiopathies (TMA) represent rare diseases requiring a high skill for their management that deserved in France the identification of a dedicated National reference center. TMA are short-term life-threatening diseases; however, with an adapted management, their prognosis can be excellent. It is therefore mandatory to recognize and treat them rapidly according to standard guidelines. Telemedicine is a specialized hub consisting of highly skilled staff trained in a specific domain of medicine. The telemedicine activity of a reference center is an important representative indicator of its expertise and recourse ability. It requires to be accurately evaluated and promoted. In this work, we report the French reference center for TMA telemedicine activity since its setting-up. TMA represent an interesting model of diseases that required a specific organization of telemedicine activity to adapt to clinicians demand, which includes particularly the need to answer resorts in real time 24/7. PMID- 26681106 TI - [Hyperammonemic encephalopathy as the presenting feature of a relapsing multiple myeloma]. AB - INTRODUCTION: Hyperammonemia attributed to multiple myeloma has been rarely reported. CASE REPORT: We report a 63-year-old man who was admitted to an intensive care unit for confusion and altered mental status progressing to coma that was related to a relapsing multiple myeloma. Chemotherapy allowed the reduction of serum ammonia and the return to a normal state of consciousness. CONCLUSION: Hyperammonemic encephalopathy is a rare complication of multiple myeloma and is associated with high in-patient mortality. To our knowledge, this is the first case of hyperammonemic encephalopathy due to a relapsing myeloma diagnosed and treated in intensive care unit. PMID- 26681107 TI - Development of a Carbon Mesh Supported Thin Film Microextraction Membrane As a Means to Lower the Detection Limits of Benchtop and Portable GC/MS Instrumentation. AB - In this work, a durable and easy to handle thin film microextraction (TFME) device is reported. The membrane is comprised of poly(divinylbenzene) (DVB) resin particles suspended in a high-density polydimethylsiloxane (PDMS) glue, which is spread onto a carbon fiber mesh. The currently presented membrane was shown to exhibit a substantially lesser amount of siloxane bleed during thermal desorption, while providing a statistically similar extraction efficiency toward a broad spectrum of analytes varying in polarity when compared to an unsupported DVB/PDMS membrane of similar shape and size which was prepared with previously published methods. With the use of hand-portable GC-TMS instrumentation, membranes cut with dimensions 40 mm long by 4.85 mm wide and 40 +/- 5 MUm thick (per side) were shown to extract 21.2, 19.8, 18.5, 18,4, 26.8, and 23.7 times the amount of 2,4 dichlorophenol, 2,4,6 trichlorophenol, phorate D10, fonofos, chloropyrifos, and parathion, respectively, within 15 min from a 10 ppb aqueous solution as compared to a 65 MUm DVB/PDMS solid phase microextraction (SPME) fiber. A portable high volume desorption module prototype was also evaluated and shown to be appropriate for the desorption of analytes with a volatility equal to or lesser than benzene when employed in conjunction with TFME membranes. Indeed, the coupling of these TFME devices to hand-portable gas chromatography toroidial ion trap mass spectrometry (GC-TMS) instrumentation was shown to push detection limits for these pesticides down to the hundreds of ppt levels, nearing that which can be achieved with benchtop instrumentation. Where these membranes can also be coupled to benchtop instrumentation it is reasonable to assume that detection limits could be pushed down even further. As a final proof of the concept, the first ever, entirely on-site TFME-GC-TMS analysis was performed at a construction impacted lake. Results had indicated the presence of contaminants such as toluene, ethylbenzene, xylene, 2,2,4-trimethyl-1,3-pentanediol diisobutyrate, and tris(1-chloro-2-propyl)phosphate, which stood out from other naturally occurring compounds detected. PMID- 26681109 TI - Growth and Stress-induced Transformation of Zinc blende AlN Layers in Al-AlN-TiN Multilayers. AB - AlN nanolayers in sputter deposited {111}Al/AlN/TiN multilayers exhibit the metastable zinc-blende-structure (z-AlN). Based on density function theory calculations, the growth of the z-AlN is ascribed to the kinetically and energetically favored nitridation of the deposited aluminium layer. In situ nanoindentation of the as-deposited {111}Al/AlN/TiN multilayers in a high resolution transmission electron microscope revealed the z-AlN to wurzite AlN phase transformation through collective glide of Shockley partial dislocations on every two {111} planes of the z-AlN. PMID- 26681110 TI - Homogeneity of lithium distribution in cylinder-type Li-ion batteries. AB - Spatially-resolved neutron powder diffraction with a gauge volume of 2 * 2 * 20 mm(3) has been applied as an in situ method to probe the lithium concentration in the graphite anode of different Li-ion cells of 18650-type in charged state. Structural studies performed in combination with electrochemical measurements and X-ray computed tomography under real cell operating conditions unambiguously revealed non-homogeneity of the lithium distribution in the graphite anode. Deviations from a homogeneous behaviour have been found in both radial and axial directions of 18650-type cells and were discussed in the frame of cell geometry and electrical connection of electrodes, which might play a crucial role in the homogeneity of the lithium distribution in the active materials within each electrode. PMID- 26681111 TI - Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain. AB - OBJECTIVE: To evaluate long-term use of Hysingla((r)) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. METHODS: This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naive or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale Revised and concomitant nonstudy opioid analgesic use. RESULTS: Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment emergent adverse events were typical of those observed with MU-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. CONCLUSIONS: HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of treatment. PMID- 26681112 TI - Work-related injuries to animal care workers, Washington 2007-2011. AB - BACKGROUND: For workers engaged in animal care, workplace hazards are common and may outnumber those experienced by human healthcare workers. METHODS: We used accepted Washington State workers' compensation claims for the period from January 1, 2007 and December 31, 2011 to compare injury rates and types of injuries across animal care occupations. RESULTS: Work-related injuries frequently affect veterinary support staff and those working in pet stores, shelters, grooming facilities and kennels. Animal-related injuries were the most commonly reported injury type experienced by all groups, though the animal source of injury appears to differ by work setting. CONCLUSIONS: Workplace related injuries among animal care workers are common and most often caused by physical insults resulting from worker-animal interaction. PMID- 26681113 TI - Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. AB - The connection between the innate immune system, clock genes, and mitochondrial bioenergetics was analyzed during aging and sepsis in mouse heart. Our results suggest that the sole NF-kappaB activation does not explain the inflammatory process underlying aging; the former also triggers the NLRP3 inflammasome that enhances caspase-1-dependent maturation of IL-1beta. In this way, aged mice enter into a vicious cycle as IL-1beta further activates the NF-kappaB/NLRP3 inflammasome link. The origin of NF-kappaB activation was related to the age dependent Bmal1/Clock/RORalpha/Rev-Erbalpha loop disruption, which lowers NAD(+) levels, reducing the SIRT1 deacetylase ability to inactivate NF-kappaB. Consequently, NF-kappaB binding to DNA increases, raising the formation of proinflammatory mediators and inducing mitochondrial impairment. The cycle is then closed with the subsequent NLRP3 inflammasome activation. This paired contribution of the innate immune pathways serves as a catalyst to magnify the response to sepsis in aged compared with young mice. Melatonin administration blunted the septic response, reducing inflammation and oxidative stress, and enhancing mitochondrial function at the levels of nonseptic aged mice, but it did not counteract the age-related inflammation. Together, our results suggest that, although with different strengths, chronoinflammaging constitutes the biochemical substrate of aging and sepsis, and identifies the NLRP3 inflammasome as a new molecular target for melatonin, providing a rationale for its use in NLRP3 dependent diseases. PMID- 26681114 TI - Temporal and Spatial Analysis of the New World Screwworm (Cochliomyia hominivorax) in Darien and Embera, Panama (2001-2011). AB - Larvae (maggots) of Cochliomyia hominivorax, the New World Screwworm fly, are voracious consumers of living flesh that have a negative economic impact by decreasing productivity, predisposing to other pathogens, and, in severe cases, causing death of domestic livestock. Screwworm caused extensive financial losses to the livestock industry in North America prior to its eradication. Sterile insect technique (SIT) was used to eradicate screwworm throughout North and Central America and continues to be the main tool to control it in eastern Panama. The goal of this study was to evaluate the temporal and spatial trends of screwworm myiasis cases reported in the Province of Darien and Comarca Embera (border with Colombia), Panama, from 2001 to 2011. We hypothesized that screwworm cases would vary seasonally and be spatially clustered near Colombia as a result of effective eradication strategies in Panama and the presence of an autochthonous population of flies in western Colombia. Temporal and spatial data were retrieved from COPEG-USDA records (Panama) and analysed by anova, Ripley's K function, discrete Poisson spatial statistic scan and Getis-Ord Gi*. No significant temporal trend was found, but cases were spatially distributed in four clusters. One cluster of cases occurred from 2001 to 2003 and was considered a focal temporal and spatial cluster. One cluster occurred in 2001 and 2007 indicating more rare outbreaks in an area with fewer cattle. The two remaining clusters contained cases from 2004 to 2011 and 2001 to 2011 suggesting regular breaks in the control barrier due to occasional failures of the SIT programme, difficulties implementing border quarantine strategies, livestock smuggling or the movement of infested wildlife. PMID- 26681115 TI - Some Words Hurt More Than Others: Semantic Activation of Pain Concepts in Memory and Subsequent Experiences of Pain. AB - Theory suggests that as activation of pain concepts in memory increases, so too does subsequent pain perception. Previously, researchers have found that activating pain concepts in memory increases pain perception of subsequent painful stimuli, relative to neutral information. However, they have not attempted to quantify the nature of the association between information studied and ensuing pain perception. We subliminally presented words that had either a low or high degree of association to the word 'pain,' although this was only partially successful and some words were consciously perceived. Participants then received randomized laser heat stimuli, delivered at 1 of 3 intensity levels (low, moderate, high), and we measured the effect of this on behavioral and electrophysiological measures of pain. Participants (N = 27) rated moderate- and high-intensity laser stimuli as more painful after viewing high relative to low associates of pain; these effects remained present when we controlled for measures of mood, anxiety, and physical symptom reporting. Similar effects were observed physiologically, with higher stimulus negativity preceding after high relative to low associates and greater amplitudes for the N2 component of the laser-evoked potential after presentation of high associates in the moderate and high laser intensity conditions. These data support activation-based models of the effects of memory on pain perception. PERSPECTIVE: Consistent with current theories of memory and pain, we found that high, relative to low activation of pain concepts in memory increased psychological and physiological responses to laser-induced pain. The effect remained regardless of whether participants showed conscious awareness of activation. Theoretical and clinical implications are discussed. PMID- 26681116 TI - Response to 'Is it safe to perform a controlled ovarian stimulation for assisted reproduction in young breast cancer survivors?'. PMID- 26681119 TI - What is the truth behind pump thrombosis in the HeartMate II device? A National Heart, Lung, and Blood Institute perspective based on data from the Interagency Registry for Mechanically Assisted Circulatory Support. PMID- 26681120 TI - Pump thrombosis redux. PMID- 26681121 TI - Pump thrombosis in the Thoratec HeartMate II device: An update analysis of the INTERMACS Registry. AB - BACKGROUND: Pump thrombosis in durable continuous-flow pumps is a barrier to long term mechanical circulatory support. Earlier Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data identified an increasing risk of pump thrombosis in recent years with the HeartMate II (HMII) left ventricular assist device. The current analysis examines pump thrombosis in the patient cohort extended through June 2014. METHODS: The INTERMACS identified 9,808 adult patients from 144 institutions receiving a primary HMII implant between April 2008 and June 30, 2014. Pump thrombosis was identified at time of explant, transplant or death. Risk factors for pump thrombosis were examined by multivariable analysis in the hazard function domain. The association between pump thrombosis and implant year was modeled in the hazard domain. RESULTS: Parametric hazard modeling of thrombosis by year of implant identified an increasing risk of pump thrombosis from 2009 through 2013, followed by a decrease in the risk during the first half of 2014, which was most apparent during the first 3 months post-implant. Risk factors for pump thrombosis included younger age (p < 0.001), higher body mass index (p = 0.02), history of non-compliance (p = 0.004), severe right heart failure (p = 0.02), later date of implant (p < 0.0001), and elevated lactate dehydrogenase during the first month post-implant (p < 0.0001). Subsequent pump thrombosis was more likely if the initial pump exchange indication was pump thrombosis (p < 0.0001). CONCLUSIONS: The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014. Identification of marked elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies. PMID- 26681117 TI - Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution. AB - Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~ 5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer. PMID- 26681122 TI - Current risks of HeartMate II pump thrombosis: Non-parametric analysis of Interagency Registry for Mechanically Assisted Circulatory Support data. AB - BACKGROUND: Data from 3 institutions revealed an abrupt increase in HeartMate II (Thoratec) pump thrombosis starting in 2011, associated with 48% mortality at 6 months without transplantation or pump exchange. We sought to discover if the increase occurred nationwide in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data, and if so (1) determine if accelerated risk continued, (2) identify predictors, (3) investigate institutional variability, and (4) assess mortality after pump thrombosis. METHODS: From April 2008 to June 2014, 11,123 HeartMate II devices were implanted at 146 institutions. Machine learning, non-parametric Random Forests for Survival was used to explore risk adjusted thrombosis based on 87 pre-implant and implant variables, including implant date. RESULTS: A total of 995 pumps thrombosed, with risk peaking within weeks of implant. The risk-adjusted increase in pump thrombosis began in 2010, reached a maximum in 2012, and then plateaued at a level that was 3.3-times higher than pre-2010. Pump exchange, younger age, and larger body mass index were important predictors, and institutional variability was largely explained by implant date, patient profile, and duration of support. The probability of death within 3 months after pump thrombosis was 24%. CONCLUSIONS: Accelerated risk of HeartMate II thrombosis was confirmed by Interagency Registry for Mechanically Assisted Circulatory Support data, with risk subsequently leveling at a risk adjusted rate higher than observed pre-2010. This elevated thrombosis risk emphasizes the need for improved mechanical circulatory support systems and post market surveillance of adverse events. Clinicians cognizant of these new data should incorporate them into their and their patients' expectations and understanding of risks relative to those of transplantation and continued medical therapy. PMID- 26681123 TI - Treatment of device thrombus in the HeartWare HVAD: Success and outcomes depend significantly on the initial treatment strategy. AB - BACKGROUND: Pump thrombosis is a major adverse event in patients supported with a left ventricular assist device (LVAD). Treatment approaches include device exchange, lytic therapy, or augmentation of anticoagulation or antiplatelet therapy. The optimal strategy in the HeartWare HVAD Ventricular Assist System (HeartWare, Framingham, MA) is uncertain, and because few large studies have examined differing treatment outcomes, we have reviewed findings from the Mechanical Circulatory Support Research Network registry. METHODS: Between March 2009 and August 2014, 175 patients (133 male) underwent implantation of the HeartWare HVAD at institutions that comprise the Mechanical Circulatory Support Research Network. Median age at implant was 59 years (range, 18-76 years). Follow up was available in all patients for a median of 6 months (maximum, 61 months) and for a total of 163 patient-years of support. There were 36 pump thromboses (using Interagency Registry for Mechanically Assisted Circulatory Support criteria) in 21 patients for a total event rate of 0.22 events/patient-year of support; 13 patients had 1 event, 4 had 2, 2 had 3, 1 had 4, and 1 had 5. The median time to the first thrombosis was 6.4 months, and to each subsequent thrombosis was 4, 3, 2, and 2 months, respectively. Primary treatment success was defined as the patient remaining alive and within the first 30 days of the initial treatment be free from stroke, recurrence of pump thrombosis, device exchange, or urgent transplantation (United Network of Organ Sharing Status 1A). Medical treatment was defined as tissue plasminogen activator, heparin plus glycoprotein IIb/IIIa inhibitor, or heparin alone, not followed by surgical treatment within 72 hours. RESULTS: Initial medical treatment was used in 29 episodes (tissue plasminogen activator in 24, heparin alone in 4, and heparin plus glycoprotein IIb/IIIa in 1) and surgical (device exchange) in 7. Medical treatment was successful in 14 of 29 episodes (48%). Complications of medical treatment included hemorrhagic stroke in 6 patients (21%), need for urgent device exchange/transplant in 6 (21%), and death in 3 (10%). Surgical treatment was successful in all 7 patients (100%). No significant early complications or early deaths occurred after device exchange. CONCLUSIONS: In this large multicenter analysis, we observed that medical therapy, as the initial treatment strategy for HeartWare HVAD thrombosis, is associated with low success (48%) and a significant risk of hemorrhagic stroke (21%) and death (10%). However, initial treatment with device exchange was uniformly successful and not associated with significant early morbidity or death. Although the optimal treatment approach for HeartWare HVAD pump thrombosis remains undecided, these data do not support the routine use of medical therapy as an initial treatment strategy. PMID- 26681125 TI - Cerebral protection system applied during washout of thrombus occluding inflow cannula of HeartWare HVAD left ventricular assist device. PMID- 26681124 TI - Benefits of a novel percutaneous ventricular assist device for right heart failure: The prospective RECOVER RIGHT study of the Impella RP device. AB - BACKGROUND: Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP (Abiomed, Danvers, MA), in a prospective, multicenter trial. METHODS: Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy. RESULTS: The patients (77% male) were a mean age of 59 +/- 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 +/- 0.2 to 3.3 +/- 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 +/- 4 to 12.6 +/- 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 +/- 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days. CONCLUSIONS: In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population. PMID- 26681126 TI - Prevalence of Intraventricular Conduction Disturbances in a Large French Population. AB - BACKGROUND: Recommendations for the interpretation of electrocardiogram have been published in 2009. The aim of this study was to define the prevalence of intraventricular conduction disturbances (ICoDs) in a large population, using these recommendations. METHODS: From 01/31/1996 to 09/22/2010, an electrocardiogram was performed at each visit for all aircrew members examined for fitness assessment in an aeromedical center. The prevalence of left bundle branch block (LBBB), right bundle branch block (RBBB), incomplete LBBB, incomplete RBBB, nonspecific intraventricular disturbance (NIVCD), left anterior fascicular block (LAFB), and left posterior fascicular block (LPFB) was measured and compared by age and gender. RESULTS: The global prevalence of ICoD was 3.09% in our population of 69,186 patients. The most frequent types of ventricular blocks were IRBBB (1.25%) and LAFB (1.10%), whereas RBBB (0.46%), LBBB (0.08%), ILBBB (0.03%), NIVCD (0.05%), and LPFB (0.13%) were rare findings. ICoDs are more frequent for males and older age groups (P < 0.001). DISCUSSION: Our results are comparable to studies concerning low cardiovascular risks populations. The association between ICoD and cardiovascular diseases needs to be studied in this population. PMID- 26681127 TI - Bridging Lung Development with Chronic Obstructive Pulmonary Disease. Relevance of Developmental Pathways in Chronic Obstructive Pulmonary Disease Pathogenesis. AB - Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation. This generic term encompasses emphysema and chronic bronchitis, two common conditions, each having distinct but also overlapping features. Recent epidemiological and experimental studies have challenged the traditional view that COPD is exclusively an adult disease occurring after years of inhalational insults to the lungs, pinpointing abnormalities or disruption of the pathways that control lung development as an important susceptibility factor for adult COPD. In addition, there is growing evidence that emphysema is not solely a destructive process because it is also characterized by a failure in cell and molecular maintenance programs necessary for proper lung development. This leads to the concept that tissue regeneration required stimulation of signaling pathways that normally operate during development. We undertook a review of the literature to outline the contribution of developmental insults and genes in the occurrence and pathogenesis of COPD, respectively. PMID- 26681128 TI - Residential context, institutional alloparental care, and child growth in Jamaica. AB - OBJECTIVES: Although children are typically raised in familial care networks, not all children have access to kin. Here, I investigate the growth measures of children living in two different residential contexts in Jamaica: institutional care settings and familial homes. METHODS: This cross-sectional study sampled individuals ranging from 5-18 years old, residing in children's homes (N = 113 participants) and familial homes (N = 103 participants). Anthropometric measurements and interview data were collected from all participants. Height for age z-scores (ZHFA) and weight for age z-scores (ZWFA) were calculated using the 2007 WHO standards. Body fat was estimated from tricep and suprailiac skinfold thickness. Between group comparisons were completed using analysis of covariance (ANCOVA), with age included as a covariate. Significance was accepted at P <= 0.05. RESULTS: Context was more predictive of condition among children than adolescents. Both girls and boys ages 5-11 years living with family members had higher mean height and weight for age, and summed skinfold thickness measures, than their peers living in children's homes. Fewer correlations between home setting and growth measurements were found among 12-18 year olds. Notably, although children were randomly assigned to children's homes, boys in a single sex institution did not differ in growth measurements from boys living with family members. CONCLUSIONS: Younger children who lived with family members had better growth measurements than their peers living in institutional settings. However, improved growth measures for children living in one home were correlated to nonconventional counseling practices, and nutritional policies that mirror some aspects of familial care. Am. J. Hum. Biol. 28:493-502, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26681129 TI - Epidemiologic characteristics and time trend in the prevalence of anotia and microtia in China. AB - BACKGROUND: Previous studies have shown an inconsistent time trend on the prevalence of anotia and microtia. Little has been reported on the epidemiologic characteristics of anotia and microtia in the Chinese population. METHODS: Data from 1996-2007 were obtained from the Chinese Birth Defects Monitoring Network in China. Birth prevalence of anotia and microtia were assessed according to demographic characteristics and annual time trend. Poisson regression was used to calculate crude and adjusted prevalence ratios (APRs) and 95% confidence intervals (CIs) for selected demographic characteristics and subgroups of anotia and microtia. RESULTS: A total of 1933 cases with anotia/microtia were identified among 6,308,594 live births, stillbirths, and terminations of pregnancy, yielding a rate of 3.06 per 10,000 births. Isolated anotia/microtia had a prevalence of 2.25 per 10,000 births, whereas among nonisolated cases, the prevalence was 0.81 per 10,000 births. The prevalence rates of anotia/microtia increased significantly during 1996-2007 (p < 0.05). Birth prevalence of isolated anotia/microtia was significantly higher among western births (APR, 1.24; 95% CI, 1.10-1.40), mothers residing in urban areas (APR, 1.29; 95% CI, 1.15-1.46), mothers more than 35 years of age (APR, 1.26; 95% CI, 1.01-1.57), and males (APR, 1.38; 95% CI, 1.24-1.53). No significant associations were observed between nonisolated anotia/microtia and geographic areas, maternal residence, and infant sex (except for maternal age). CONCLUSION: An increasing trend of the birth prevalence of anotia and microtia is observed in China. Higher prevalence risk of isolated anotia and microtia is found among western births, mothers residing in urban areas, older mothers, and males. PMID- 26681130 TI - Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression. AB - INTRODUCTION: Urinary trypsin inhibitor (UTI) decreases inflammatory cytokine levels and mortality in experimental animal models of inflammation. Here, we observed the effect of UTI on lipopolysaccharide (LPS)-induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) and explored the role of vascular endothelial-cadherin (VE-cadherin) in its effect. METHODS: The effect of UTI on endothelial barrier hyperpermeability was detected by an electrical cell substrate impedance sensing (ECIS) system and a transwell chamber system. The expression of VE-cadherin in HUVECs was examined by real-time PCR and western blot. RESULTS: We demonstrated that the alleviation of LPS-induced barrier dysfunction could be achieved by pretreatment with 3000 U/mL of UTI. VE-cadherin monoclonal antibody (mAb) could inhibit the protective effects. UTI maintained VE cadherin expression by increasing protein stability at both the transcriptional and post-transcriptional levels. Meanwhile, VE-cadherin expression on the cell surface increased when the cells were pretreated with UTI. Furthermore, pretreatment with UTI decreased the phosphorylation of VE-cadherin at Tyr658 but not Tyr731. CONCLUSIONS: Our data show that prophylactic UTI maintains the endothelial barrier function, increases VE-cadherin expression, and inhibits the phosphorylation of VE-cadherin at Tyr658 under inflammatory conditions. It suggests a scientific and potential clinical therapeutic importance of UTI in treatment of inflammatory disorders. PMID- 26681131 TI - Corrigendum: Donkey genome and insight into the imprinting of fast karyotype evolution. PMID- 26681133 TI - Cocoa Flavanols: A Magic Potion for Protecting the Endothelium in Kidney Failure? PMID- 26681132 TI - Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial. AB - BACKGROUND AND OBJECTIVES: Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics. RESULTS: CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2+/-0.6% to 4.8+/-0.9% versus placebo, 3.2+/-0.7% to 3.3+/-0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4+/-0.9% to 3.9+/-0.8% versus placebo, 3.5+/-0.7% to 3.5+/-0.7%; P<0.001), with reduced diastolic BP (73+/-12 to 69+/-11 mmHg versus placebo, 70+/-11 to 73+/-13 mmHg; P=0.03) and increased heart rate (70+/-12 to 74+/-13 bpm versus placebo, 75+/-15 to 74+/-13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4+/-0.9% to 2.7+/-0.6% versus placebo, 3.5+/-0.7% to 2.0+/-0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9+/-0.9% to 3.0+/-0.7% versus placebo, 3.5+/-0.7% to 2.2+/-0.6; P=0.01). CONCLUSIONS: Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD. PMID- 26681134 TI - Waiting for a Deceased Kidney Donor Transplant: Better a Small Fish Than an Empty Dish? PMID- 26681136 TI - Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors. AB - BACKGROUND AND OBJECTIVES: The quality and age of donor organs are known to have a major effect on patient and graft outcomes, but it is uncertain whether this association is uniform for all recipients. We aimed to determine whether the use of expanded criteria deceased donor (ECD) kidneys for transplantation compared with standard criteria deceased donor (SCD) kidneys has a different association with survival in younger (age <60 years old) compared with older (age >=60 years old) recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the Australian and New Zealand Dialysis and Transplant Registry (1997-2009), we compared the risk of all-cause mortality and death with functioning graft among younger and older recipients who had received either an SCD or an ECD kidney using the adjusted Cox proportional hazard models. RESULTS: In total, 3822 patients were transplanted between 1997 and 2009. Over a follow-up period of 21,249 person-years (a median duration of 5.3 years [interquartile range, 2.22 8.6 years]), 567 recipients (n=385 for those age <60 years old; n=182 for those age >=60 years old) died. Recipient age was an effect modifier between donor types, all-cause mortality, and death with functioning graft (P values for interaction were 0.05 and 0.04, respectively). In younger recipients, there was an excess risk of all-cause mortality (adjusted hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.23 to 1.97) and death with functioning graft (adjusted HR, 1.72; 95% CI, 1.28 to 2.29) after transplantation with ECD kidneys compared with SCD kidneys, but there was no statistically significant association among older recipients (adjusted HR, 1.11; 95% CI, 0.80 to 1.54 and adjusted HR, 1.30; 95% CI, 0.89 to 1.89, respectively). This excess risk was largely caused by death from cardiovascular disease. CONCLUSIONS: There was an excess risk of all cause mortality and death with functioning graft when younger recipients were transplanted with ECD kidneys compared with SCD kidneys. These findings suggest that caution is needed in allocating ECD kidneys to younger recipients. PMID- 26681135 TI - Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge. AB - BACKGROUND AND OBJECTIVES: Observational evidence has suggested that RRT modality may affect recovery after AKI. It is unclear whether initial choice of intermittent hemodialysis or continuous RRT affects renal recovery, survival, or development of ESRD in critically ill patients when modality choice is made primarily on hemodynamics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study examining adults (>=18 years old) admitted to intensive care units from 2000 to 2008 who received RRT for AKI and survived to hospital discharge or 90 days. We analyzed renal recovery (alive and not requiring RRT) and reasons for nonrecovery (death or ESRD) at 90 and 365 days. Conditional multivariable logistic regression was used to assess differences in renal recovery at 90 and 365 days between continuous RRT and intermittent hemodialysis. Models were stratified by propensity for continuous RRT and adjusted for age and reference creatinine. RESULTS: Of 4738 patients with Kidney Disease Improving Global Outcomes stage 3 AKI, 1338 (28.2%) received RRT, and 638 (47.7%) survived to hospital discharge (353 intermittent hemodialysis and 285 continuous RRT). Recovery from AKI was lower for intermittent hemodialysis versus continuous RRT at 90 days (66.6% intermittent hemodialysis versus 75.4% continuous RRT; P=0.02) but similar at 365 days (54.1% intermittent hemodialysis versus 59.6% continuous RRT; P=0.17). In multivariable analysis, there was no difference in odds of recovery at 90 or 365 days for patients initially treated with continuous RRT versus intermittent hemodialysis (90 days: odds ratio, 1.19; 95% confidence interval, 0.91 to 1.55; P=0.20; 365 days: odds ratio, 0.93; 95% confidence interval, 0.72 to 1.2; P=0.55). CONCLUSIONS: We found no significant difference in hazards for nonrecovery or reasons for nonrecovery (mortality or ESRD) with intermittent hemodialysis versus continuous RRT. These results suggest that, when initial RRT modality is chosen primarily on hemodynamics, renal recovery and clinical outcomes in survivors are similar between intermittent hemodialysis and continuous RRT. PMID- 26681137 TI - DNA barcoding for squids of the family Gonatidae (Cephalopoda: Teuthida) from the boreal North Pacific. AB - A fragment of cytochrome c oxidase I was used to assess whether species of the squid family Gonatidae from the North Pacific could be identified using DNA barcoding approach. Pairwise intra- and interspecific p-distances were assessed, and systematic relationships among species were estimated by NJ analysis. Examined species formed well-differentiated species-specific clades on the neighbor-joining and Bayesian trees. Multiple taxa formed clades supported by both tree topologies and species hypothesis-free ABGD method. Species morphologically identified as Gonatus tinro and Gonatopsis okutanii demonstrated intraspecific level of molecular genetic divergence (0.2-0.3%) indicating that they are conspecific. Genetic differences between the G. berryi clade and a squid morphologically close to that species may indicate a new cryptic species. High levels (>6.2%) of genetic differentiation within B. borealis suggested the existence of two cryptic species. This study confirms the usefulness of DNA barcoding for identifying species as well as discovering cryptic diversity in the gonatid squids, and indicates the need for further deeper insights into the phylogeny of the Gonatidae. PMID- 26681138 TI - Intra-articular administration of lidocaine plus adrenaline in dogs: Pharmacokinetic profile and evaluation of toxicity in vivo and in vitro. AB - The aim of this study was to evaluate the safety of intra-articular (IA) lidocaine plus adrenaline for improving peri-operative analgesia in anaesthetized dogs undergoing arthroscopy of the elbow. A solution of lidocaine (L) 1.98% plus adrenaline 1:100.000 was administered via the IA route and its safety evaluated in terms of cardio-, neuro-, and chondro-toxicity. No bradycardia or hypotension was recorded from induction to the last observational time point. Signs of toxicity of the nervous system could have been masked by the general anaesthesia but lidocaine concentrations detected in the blood were lower than those thought to be capable of producing toxicity. The assessment of in vitro chondrotoxicity showed a dose- and time-dependent effect of lidocaine on the viability of articular cells. Adrenaline appeared to reduce the chondrotoxicity of 1% lidocaine, following an exposure of up to 30 min. PMID- 26681140 TI - Changing horses at The Veterinary Journal .... PMID- 26681139 TI - Pharmacokinetics and disposition of flupirtine in the horse. AB - Flupirtine (FLU) is a non-opioid analgesic drug, with no antipyretic or anti inflammatory effects, used in the treatment of a wide range of pain states in human beings. It does not induce the side effects associated with the classical drugs used as pain relievers. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy horses. Six mixed breed adult mares were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 * 2 Latin-square). Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The animals then swapped groups after a 1-week wash-out period and the doses were repeated. Blood samples (5 mL) were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method. Some mild and transient adverse effects (that spontaneously resolved within 5 min) were observed in 2/6 animals after IV administration. No adverse effects were noticed in the PO administration group. After IV and PO administrations, FLU was detectable in plasma for up to 36 h. The mean elimination half-life was longer after PO (10.27 h) than after IV (3.02 h) administration. The oral bioavailability was 71.4 +/- 33.1%. After compartmental simulation/modelling, an oral dose of 2.6 mg/kg was calculated to give Cmax and AUC values in horses similar to those reported in humans after a clinical dose administration with a theoretical FLU effective plasma concentration of 187 ng/mL. These findings may form the basis for further studies concerning this active ingredient in equine medicine. PMID- 26681141 TI - Pharmacokinetics of oxytetracycline in broiler chickens following different routes of administration. AB - The aim of this study was to determine the pharmacokinetics of oxytetracycline (OTC) in broiler chickens following intravenous (IV), intramuscular (IM), subcutaneous (SC) and oral (PO) administrations at a dose of 15 mg/kg bodyweight. Plasma concentrations of OTC were determined using liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic analysis was then conducted. The absorption half-life time was 1.23 +/- 0.36 h, 1.19 +/- 0.52 h, and 0.49 +/- 0.38 h after IM, SC and PO administration, respectively. The elimination half-life time was 27.41 +/- 6.06 h, 10.23 +/- 4.20 h, 7.83 +/- 0.56 h, and 14.86 +/- 9.23 h, and the mean residence time was 9.67 +/- 1.7 h, 11.45 +/ 1.76 h, 11.38 +/- 0.59 h, and 10.37 +/- 3.91 h after IV, IM, SC and PO administration, respectively. Bioavailability was 76.88 +/- 12.90%, 92.20 +/- 10.53% and 12.13 +/- 4.56% after IM, SC and PO administration, respectively, which indicated that OTC is poorly absorbed from the gastrointestinal tract in broiler chickens. PMID- 26681142 TI - Mapping Chemical Selection Pathways for Designing Multicomponent Alloys: an informatics framework for materials design. AB - A data driven methodology is developed for tracking the collective influence of the multiple attributes of alloying elements on both thermodynamic and mechanical properties of metal alloys. Cobalt-based superalloys are used as a template to demonstrate the approach. By mapping the high dimensional nature of the systematics of elemental data embedded in the periodic table into the form of a network graph, one can guide targeted first principles calculations that identify the influence of specific elements on phase stability, crystal structure and elastic properties. This provides a fundamentally new means to rapidly identify new stable alloy chemistries with enhanced high temperature properties. The resulting visualization scheme exhibits the grouping and proximity of elements based on their impact on the properties of intermetallic alloys. Unlike the periodic table however, the distance between neighboring elements uncovers relationships in a complex high dimensional information space that would not have been easily seen otherwise. The predictions of the methodology are found to be consistent with reported experimental and theoretical studies. The informatics based methodology presented in this study can be generalized to a framework for data analysis and knowledge discovery that can be applied to many material systems and recreated for different design objectives. PMID- 26681143 TI - Photobiomodulation in promoting wound healing: a review. AB - Despite diverse methods being applied to induce wound healing, many wounds remain recalcitrant to all treatments. Photobiomodulation involves inducing wound healing by illuminating wounds with light emitting diodes or lasers. While used on different animal models, in vitro, and clinically, wound healing is induced by many different wavelengths and powers with no optimal set of parameters yet being identified. While data suggest that simultaneous multiple wavelength illumination is more efficacious than single wavelengths, the optimal single and multiple wavelengths must be better defined to induce more reliable and extensive healing of different wound types. This review focuses on studies in which specific wavelengths induce wound healing and on their mechanisms of action. PMID- 26681144 TI - Insulin inhibits inflammation and promotes atherosclerotic plaque stability via PI3K-Akt pathway activation. AB - Toll-like receptor (TLR) 4 induced inflammation was reported to play an important role in atherosclerotic plaque stability. Recent studies indicated that insulin could inhibit inflammation by activating phosphatidylinositol 3-kinase-Akt dependent (PI3K-Akt) signaling pathway. In the current study, we hypothesized that insulin would inhibit TLR4 induced inflammation via promoting PI3K-Akt activation, thus enhancing the stabilization of atherosclerotic plaques. In order to mimic the process of plaque formation, monocyte-macrophage lineage RAW264.7 were cultured and induced to form foam cells by oxidized LDL (ox-LDL). Oil red O staining results showed that insulin significantly restrained ox-LDL-induced foam cell formation. Analysis of inflammatory reaction during foam cell formation indicated that insulin significantly down-regulated the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 levels, inhibited TLR4, myeloid differentiation primary response gene (MyD) 88 and nuclear factor (NF)-kappaB. Further mechanism analysis showed that pretreating with the PI3K blocker, wortmannin dramatically dampened the insulin-induced up-regulation of pAkt expression. Additionally, blockade of PI3K-Akt signaling also dampened the immunosuppression effect brought by insulin. Following the construction of a rodent atherosclerosis model, pretreatment of insulin resulted in an evident decrease in lipid deposition of the blood vessel wall, serum levels of TNF-alpha and IL-6, and numbers of infiltrated macrophages and foam cells. Taken together, these results suggested that insulin might inhibit inflammation and promote atherosclerotic plaque stability via the PI3K-Akt pathway by targeting TLR4-MyD88 NF-kappaB signaling. Our findings may provide a potential target for the prevention of cardiovascular disease. PMID- 26681146 TI - Fingerprick autologous blood for dry eyes and persistent epithelial defects. PMID- 26681145 TI - Long-term outcomes of neovascular glaucoma treated with and without intravitreal bevacizumab. AB - AIMS: To compare the outcomes of neovascular glaucoma (NVG) treated with and without intravitreal bevacizumab in a large case comparison study. METHODS: The study is a retrospective, comparative, case series of 163 eyes of 151 patients with NVG, including 99 treated without and 64 treated with intravitreal bevacizumab. Medical and surgical treatments for NVG were assessed. The main outcome measures were visual acuity (VA) and intraocular pressure (IOP). RESULTS: At the time of NVG diagnosis, the median VA was count fingers (CF) in the non bevacizumab group and 2/300 in the bevacizumab group. IOP (mean+/-SD) was 43.1+/ 13.0 mm Hg in the non-bevacizumab group and 40.8+/-11.5 mm Hg in the bevacizumab group. IOP (mean+/-SD) decreased to 18.3+/-13.8 mm Hg in the non-bevacizumab group and 15.3+/-8.0 mm Hg in the bevacizumab group, and the median VA was CF in both treatment groups at a mean follow-up of 12 months. Panretinal photocoagulation (PRP) substantially reduced the need for glaucoma surgery (P<0.001) in bevacizumab treated NVG eyes. CONCLUSIONS: Although bevacizumab delayed the need for glaucoma surgery, PRP was the most important factor that reduced the need for surgery. Vision and IOP in eyes with NVG treated with bevacizumab showed no long-term differences when compared with eyes that were not treated with bevacizumab. Thus, intravitreal bevacizumab serves as an effective temporizing treatment, but is not a replacement for close monitoring and definitive treatment of NVG. PRP remains the treatment modality that affects the course of NVG in terms of decreasing the need for surgery to control IOP. PMID- 26681147 TI - Intraoperative optical coherence tomography: past, present, and future. AB - To provide an overview of the current state of intraoperative optical coherence tomography (OCT). Literature review of studies pertaining to intraoperative OCT examining both the technology aspects of the imaging platform and the current evidence for patient care. Over the last several years, there have been significant advances in integrative technology for intraoperative OCT. This has resulted in the development of multiple microscope-integrated systems and a rapidly expanding field of image-guided surgical care. Multiple studies have demonstrated the potential role for intraoperative OCT in facilitating surgeon understanding of the surgical environment, tissue configuration, and overall changes to anatomy. In fact, the PIONEER and DISCOVER studies, both demonstrated a potential significant percentage of cases that intraoperative OCT alters surgical decision-making in both anterior and posterior segment surgery. Current areas of exploration and development include OCT-compatible instrumentation, automated tracking, intraoperative OCT software platforms, and surgeon feedback/visualization platforms. Intraoperative OCT is an emerging technology that holds promise for enhancing the surgical care of both anterior segment and posterior segment conditions. Hurdles remain for adoption and widespread utilization, including cost, optimized feedback platforms, and more definitive value for individualized surgical care with image guidance. PMID- 26681149 TI - Sonographic features of keratoacanthoma. May ultrasound be a useful tool to differentiate it from squamous cell carcinoma? PMID- 26681148 TI - Anatomical and functional retinal changes in multiple sclerosis. AB - AIMS: The aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields. METHODS: Prospective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP. RESULTS: MS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (P<0.001). This reduction was more representative (P<0.001) in patients with MS complicated by optic neuritis (ON). We found in the MS group a strong correlation between GCC thickness and macular volume (r(2)=0.59, P<0.001) and also between GCC and RNFL thickness (r(2)=0.48, P<0.001). There was also a correlation between macular sensitivity and macular volume reduction (r(2)=0.25, P<0.001) and also between RNFL and macular volume (r(2)=0.43, P<0.001). CONCLUSIONS: The significant statistical evidence and the strong correlation between anatomical and functional parameters support the use of OCT and MP in the evaluation, treatment, and follow-up of patients diagnosed with MS. PMID- 26681150 TI - Language profiles and literacy outcomes of children with resolving, emerging, or persisting language impairments. AB - BACKGROUND: Children with language impairment (LI) show heterogeneity in development. We tracked children from pre-school to middle childhood to characterize three developmental trajectories: resolving, persisting and emerging LI. METHODS: We analyzed data from children identified as having preschool LI, or being at family risk of dyslexia, together with typically developing controls at three time points: t1 (age 3;09), t3 (5;08) and t5 (8;01). Language measures are reported at t1, t3 and t5, and literacy abilities at t3 and t5. A research diagnosis of LI (irrespective of recruitment group) was validated at t1 by a composite language score derived from measures of receptive and expressive grammar and vocabulary; a score falling 1SD below the mean of the typical language group on comparable measures at t3 and t5 was used to determine whether a child had LI at later time points and then to classify LIs as resolving, persisting or emerging. RESULTS: Persisting preschool LIs were more severe and pervasive than resolving LIs. Language and literacy outcomes were relatively poor for those with persisting LI, and relatively good for those with resolving LI. A significant proportion of children with average language abilities in preschool had LIs that emerged in middle childhood - a high proportion of these children were at family risk of dyslexia. There were more boys in the persisting and resolving LI groups. Children with early LIs which resolved by the start of formal literacy instruction tended to have good literacy outcomes; children with late-emerging difficulties that persisted developed reading difficulties. CONCLUSIONS: Children with late-emerging LI are relatively common and are hard to detect in the preschool years. Our findings show that children whose LIs persist to the point of formal literacy instruction frequently experience reading difficulties. PMID- 26681151 TI - Prediction of individual differences in adjustment to loss: Acceptance and valued living as critical appraisal and coping strengths. AB - Our strengths-based model of coping with death and dying proposes acceptance and valued-living as key coping and appraisal strengths for the bereaved. These are core components of Acceptance and Commitment Therapy (ACT). The aim of this study was to provide an initial exploration of the theorized relationships via a survey of 97 bereaved university students. Using hierarchical regression analysis it was found that acceptance and valued-living were significant predictors of grief, while controlling for other model variables and loss characteristics. Results have implications for ACT-based approaches in supporting those bereaved who are struggling with their grief. PMID- 26681152 TI - Complete mitochondrial DNA genome of Triplophysa venusta (Cypriniformes: Cobitida). AB - The complete mitochondrial DNA sequence of Triplophysa venusta was determined using a PCR-based method in our present study. The genome is totally 16 574 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, and 1 non-coding control region. The overall base composition of T. venusta is A 27.8%, T 26.9%, C 26.9%, and G 18.4%, with an A + T bias of 54.7%. This complete mitogenome of T. venusta provides a basic data for studies on species identification, molecular systematics, and conservation genetics. The phylogenetic trees consistently showed that the Family Cobitidae was divided into three major clades: the subfamily Botiidae, the subfamily Nemaeheilidae, and the subfamily Cobitinae. Cobitinae and Nomaeheilidae formed a main Loach clade, with Botiidae clustered at the basal. PMID- 26681153 TI - Evolutionary Origins of Rhizarian Parasites. AB - The SAR group (Stramenopila, Alveolata, Rhizaria) is one of the largest clades in the tree of eukaryotes and includes a great number of parasitic lineages. Rhizarian parasites are obligate and have devastating effects on commercially important plants and animals but despite this fact, our knowledge of their biology and evolution is limited. Here, we present rhizarian transcriptomes from all major parasitic lineages in order to elucidate their evolutionary relationships using a phylogenomic approach. Our results suggest that Ascetosporea, parasites of marine invertebrates, are sister to the novel clade Apofilosa. The phytomyxean plant parasites branch sister to the vampyrellid algal ectoparasites in the novel clade Phytorhiza. They also show that Ascetosporea + Apofilosa + Retaria + Filosa + Phytorhiza form a monophyletic clade, although the branching pattern within this clade is difficult to resolve and appears to be model-dependent. Our study does not support the monophyly of the rhizarian parasitic lineages (Endomyxa), suggesting independent origins for rhizarian animal and plant parasites. PMID- 26681154 TI - Evolution of a Catalytic Mechanism. AB - The means by which superfamilies of specialized enzymes arise by gene duplication and functional divergence are poorly understood. The escape from adaptive conflict hypothesis, which posits multiple copies of a gene encoding a primitive inefficient and highly promiscuous generalist ancestor, receives support from experiments showing that resurrected ancestral enzymes are indeed more substrate promiscuous than their modern descendants. Here, we provide evidence in support of an alternative model, the innovation-amplification-divergence hypothesis, which posits a single-copied ancestor as efficient and specific as any modern enzyme. We argue that the catalytic mechanisms of plant esterases and descendent acetone cyanohydrin lyases are incompatible with each other (e.g., the reactive substrate carbonyl must bind in opposite orientations in the active site). We then show that resurrected ancestral plant esterases are as catalytically specific as modern esterases, that the ancestor of modern acetone cyanohydrin lyases was itself only very weakly promiscuous, and that improvements in lyase activity came at the expense of esterase activity. These observations support the innovation-amplification-divergence hypothesis, in which an ancestor gains a weak promiscuous activity that is improved by selection at the expense of the ancestral activity, and not the escape from adaptive conflict in which an inefficient generalist ancestral enzyme steadily loses promiscuity throughout the transition to a highly active specialized modern enzyme. PMID- 26681155 TI - Barriers and Facilitators to Online Portal Use Among Patients and Caregivers in a Safety Net Health Care System: A Qualitative Study. AB - BACKGROUND: Patient portals have the potential to support self-management for chronic diseases and improve health outcomes. With the rapid rise in adoption of patient portals spurred by meaningful use incentives among safety net health systems (a health system or hospital providing a significant level of care to low income, uninsured, and vulnerable populations), it is important to understand the readiness and willingness of patients and caregivers in safety net settings to access their personal health records online. OBJECTIVE: To explore patient and caregiver perspectives on online patient portal use before its implementation at San Francisco General Hospital, a safety net hospital. METHODS: We conducted 16 in-depth interviews with chronic disease patients and caregivers who expressed interest in using the Internet to manage their health. Discussions focused on health care experiences, technology use, and interest in using an online portal to manage health tasks. We used open coding to categorize all the barriers and facilitators to portal use, followed by a second round of coding that compared the categories to previously published findings. In secondary analyses, we also examined specific barriers among 2 subgroups: those with limited health literacy and caregivers. RESULTS: We interviewed 11 patients and 5 caregivers. Patients were predominantly male (82%, 9/11) and African American (45%, 5/11). All patients had been diagnosed with diabetes and the majority had limited health literacy (73%, 8/11). The majority of caregivers were female (80%, 4/5), African American (60%, 3/5), caregivers of individuals with diabetes (60%, 3/5), and had adequate health literacy (60%, 3/5). A total of 88% (14/16) of participants reported interest in using the portal after viewing a prototype. Major perceived barriers included security concerns, lack of technical skills/interest, and preference for in-person communication. Facilitators to portal use included convenience, health monitoring, and improvements in patient-provider communication. Participants with limited health literacy discussed more fundamental barriers to portal use, including challenges with reading and typing, personal experience with online security breaches/viruses, and distrust of potential security measures. Caregivers expressed high interest in portal use to support their roles in interpreting health information, advocating for quality care, and managing health behaviors and medical care. CONCLUSIONS: Despite concerns about security, difficulty understanding medical information, and satisfaction with current communication processes, respondents generally expressed enthusiasm about portal use. Our findings suggest a strong need for training and support to assist vulnerable patients with portal registration and use, particularly those with limited health literacy. Efforts to encourage portal use among vulnerable patients should directly address health literacy and security/privacy issues and support access for caregivers. PMID- 26681156 TI - Stable isotope probing implicates a species of Cortinarius in carbon transfer through ectomycorrhizal fungal mycelial networks in Arctic tundra. PMID- 26681158 TI - Solvation Science: A New Interdisciplinary Field. PMID- 26681157 TI - Positive-unlabeled learning for the prediction of conformational B-cell epitopes. AB - BACKGROUND: The incomplete ground truth of training data of B-cell epitopes is a demanding issue in computational epitope prediction. The challenge is that only a small fraction of the surface residues of an antigen are confirmed as antigenic residues (positive training data); the remaining residues are unlabeled. As some of these uncertain residues can possibly be grouped to form novel but currently unknown epitopes, it is misguided to unanimously classify all the unlabeled residues as negative training data following the traditional supervised learning scheme. RESULTS: We propose a positive-unlabeled learning algorithm to address this problem. The key idea is to distinguish between epitope-likely residues and reliable negative residues in unlabeled data. The method has two steps: (1) identify reliable negative residues using a weighted SVM with a high recall; and (2) construct a classification model on the positive residues and the reliable negative residues. Complex-based 10-fold cross-validation was conducted to show that this method outperforms those commonly used predictors DiscoTope 2.0, ElliPro and SEPPA 2.0 in every aspect. We conducted four case studies, in which the approach was tested on antigens of West Nile virus, dihydrofolate reductase, beta-lactamase, and two Ebola antigens whose epitopes are currently unknown. All the results were assessed on a newly-established data set of antigen structures not bound by antibodies, instead of on antibody-bound antigen structures. These bound structures may contain unfair binding information such as bound-state B factors and protrusion index which could exaggerate the epitope prediction performance. Source codes are available on request. PMID- 26681159 TI - Cochrane review summary: influenza vaccines for preventing acute otitis media in infants and children. PMID- 26681160 TI - Structural Characterization of Aluminum (Oxy)hydroxide Films at the Muscovite (001)-Water Interface. AB - The formation of Al (oxy)hydroxide on the basal surface of muscovite mica was investigated to understand how the structure of the substrate controls the nucleation and growth of secondary phases. Atomic force microscopy images showed that solid phases nucleated on the surface initially as two-dimensional islands that were <=10 A in height and <=200 A in diameter after 16-50 h of reaction in a 100 MUM AlCl3 solution at pH 4.2 at room temperature. High-resolution X-ray reflectivity data indicated that these islands were gibbsite layers whose basic unit is composed of a plane of Al ions octahedrally coordinated to oxygen or hydroxyl groups. The formation of gibbsite layers is likely favored because of the structural similarity between its basal plane and the underlying mica surface. After 700-2000 h of reaction, a thicker and continuous film had formed on top of the initial gibbsite layers. X-ray diffraction data showed that this film was composed of diaspore that grew predominantly with its [040] and [140] crystallographic directions oriented along the muscovite [001] direction. These results show the structural characteristics of the muscovite (001) and Al (oxy)hydroxide film interface where presumed epitaxy had facilitated nucleation of metastable gibbsite layers which acted as a structural anchor for the subsequent growth of thermodynamically stable diaspore grown from a mildly acidic and Al-rich solution. PMID- 26681162 TI - ERRATUM. PMID- 26681161 TI - A systematic analysis of a broadly neutralizing antibody AR3C epitopes on Hepatitis C virus E2 envelope glycoprotein and their cross-reactivity. AB - BACKGROUND: Hepatitis C virus (HCV) belongs to Flaviviridae family of viruses. HCV represents a major challenge to public health since its estimated global prevalence is 2.8% of the world's human population. The design and development of HCV vaccine has been hampered by rapid evolution of viral quasispecies resulting in antibody escape variants. HCV envelope glycoprotein E1 and E2 that mediate fusion and entry of the virus into host cells are primary targets of the host immune responses. RESULTS: Structural characterization of E2 core protein and a broadly neutralizing antibody AR3C together with E1E2 sequence information enabled the analysis of B-cell epitope variability. The E2 binding site by AR3C and its surrounding area were identified from the crystal structure of E2c-AR3C complex. We clustered HCV strains using the concept of "discontinuous motif/peptide" and classified B-cell epitopes based on their similarity. CONCLUSIONS: The assessment of antibody neutralizing coverage provides insights into potential cross-reactivity of the AR3C neutralizing antibody across a large number of HCV variants. PMID- 26681164 TI - Implementing a Real-Time Electronic Data Capture System to Improve Clinical Documentation in Radiation Oncology. AB - PURPOSE: Electronic health records (EHRs) often store information as unstructured text, whereas electronic data capture (EDC) using structured fields is common in clinical trials. We implemented a web-based EDC system for routine clinical care, and describe our experience piloting this system for breast cancer patients receiving radiation therapy. METHODS: Our institution uses dictation for clinical documentation in a centralized EHR; a separate radiation therapy-specific record and-verify system contains prescriptions, schedules, and treatment documentation. The implemented EDC system collects patient, tumor, and treatment characteristics using structured data fields and merges it with data from the radiation therapy system to generate template-based notes in the EHR. Mean times to create notes using dictation versus EDC were compared. Users were surveyed about their experience. Acute toxicities were captured using the EDC system, and reported. RESULTS: The EDC system has been used by 25 providers for 1,296 patients. In the most recent month, 978 clinical notes were generated. The average clinician documentation time over a typical course of radiation was reduced from 22.4 minutes per patient with dictation, to 7.1 minutes with EDC. The user survey response rate was 100%, with 92% of respondents being either satisfied or very satisfied with their experience. The worst acute toxicities were mostly grade 1 (51%) or grade 2 (43%), with rare grade 3 (3%) events. CONCLUSIONS: We implemented an EDC system for routine clinical use in the breast radiation therapy service that resulted in significant time-savings for clinical documentation and prospective population of a database to facilitate outcomes reporting. PMID- 26681165 TI - If There Is No Change, Just Say So. PMID- 26681166 TI - Bioprocess exploration for thermostable alpha-amylase production of a deep-sea thermophile Geobacillus sp. in high-temperature bioreactor. AB - Geobacillus sp. 4j, a deep-sea high-salt thermophile, was found to produce thermostable alpha-amylase. In this work, culture medium and conditions were first optimized to enhance the production of thermostable alpha-amylase by statistical methodologies. The resulting extracellular production was increased by five times and reached 6.40 U/ml. Then, a high-temperature batch culture of the thermophile in a 15 l in-house-designed bioreactor was studied. The results showed that a relatively high dissolved oxygen (600 rpm and 15 l/min) and culture temperature of 60 degrees C facilitated both cell growth and alpha-amylase production. Thus, an efficient fermentation process was established with initial medium of pH 6.0, culture temperature of 60 degrees C, and dissolved oxygen above 20%. It gave an alpha-amylase production of 79 U/ml and productivity of 19804 U/l.hr, which were 10.8 and 208 times higher than those in shake flask, respectively. This work is useful for deep-sea high-salt thermophile culture, where efforts are lacking presently. PMID- 26681167 TI - Automatic DNA Diagnosis for 1D Gel Electrophoresis Images using Bio-image Processing Technique. AB - BACKGROUND: DNA gel electrophoresis is a molecular biology technique for separating different sizes of DNA fragments. Applications of DNA gel electrophoresis include DNA fingerprinting (genetic diagnosis), size estimation of DNA, and DNA separation for Southern blotting. Accurate interpretation of DNA banding patterns from electrophoretic images can be laborious and error prone when a large number of bands are interrogated manually. Although many bio-imaging techniques have been proposed, none of them can fully automate the typing of DNA owing to the complexities of migration patterns typically obtained. RESULTS: We developed an image-processing tool that automatically calls genotypes from DNA gel electrophoresis images. The image processing workflow comprises three main steps: 1) lane segmentation, 2) extraction of DNA bands and 3) band genotyping classification. The tool was originally intended to facilitate large-scale genotyping analysis of sugarcane cultivars. We tested the proposed tool on 10 gel images (433 cultivars) obtained from polyacrylamide gel electrophoresis (PAGE) of PCR amplicons for detecting intron length polymorphisms (ILP) on one locus of the sugarcanes. These gel images demonstrated many challenges in automated lane/band segmentation in image processing including lane distortion, band deformity, high degree of noise in the background, and bands that are very close together (doublets). Using the proposed bio-imaging workflow, lanes and DNA bands contained within are properly segmented, even for adjacent bands with aberrant migration that cannot be separated by conventional techniques. The software, called GELect, automatically performs genotype calling on each lane by comparing with an all-banding reference, which was created by clustering the existing bands into the non-redundant set of reference bands. The automated genotype calling results were verified by independent manual typing by molecular biologists. CONCLUSIONS: This work presents an automated genotyping tool from DNA gel electrophoresis images, called GELect, which was written in Java and made available through the imageJ framework. With a novel automated image processing workflow, the tool can accurately segment lanes from a gel matrix, intelligently extract distorted and even doublet bands that are difficult to identify by existing image processing tools. Consequently, genotyping from DNA gel electrophoresis can be performed automatically allowing users to efficiently conduct large scale DNA fingerprinting via DNA gel electrophoresis. The software is freely available from http://www.biotec.or.th/gi/tools/gelect. PMID- 26681168 TI - Expanding role of cytomegalovirus as a human pathogen. AB - Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality in transplant recipients, despite major advancements in preventative strategies. Antiviral prophylaxis and pre-emptive antiviral therapeutic regimens are associated with a high incidence of late-onset end-organ disease and cause drug related toxicity when overused. Therefore, the identification of risk factors for CMV replication is required. Genetic and immunological factors that predispose individuals to CMV-related clinical complications have been identified and may be instrumental for optimizing CMV treatment in the future. Evidence suggests a causal pathogenetic link between CMV-related complications and inflammatory diseases in non-canonically immunosuppressed individuals such as patients with lung injury and critically ill and cancer patients. However, a randomized clinical trial is required to determine if a causal relationship exists. PMID- 26681169 TI - A national quality registers as a tool to audit items of the fundamentals of care to older patients with hip fractures. AB - BACKGROUND: The Swedish healthcare system has a unique resource in the national quality registers. A national quality registry contains individualised data concerning patient problems, medical interventions and outcomes after treatment, within all healthcare settings. Many healthcare settings face challenges related to the way they deliver the fundamentals of care, therefore, it is important to audit the outcome. It is estimated that the number of people aged 80 years or older will have almost quadrupled between 2000 and 2050. Hip fracture has been recognised as the most serious consequence of osteoporosis because of the risk of its complications, which include pain, acute confusional state, pressure ulcers, infections, disability, diminished quality of life and mortality. The aim of this study was therefore to explore if and how a national quality register can be used as an audit tool for the fundamentals of care when it concerns older patients suffering from a hip fracture. METHOD: For this study we retrospectively selected and audited variables retrieved from the national quality hip fracture register. The audit included 1083 patients 80 years and older, consecutively admitted to a university hospital in the south of Sweden, in 2011-2013. RESULTS: Nearly half of the patients were admitted from their own homes and were living alone. Almost half of the patients could walk outdoors before the fracture occurred. After 4 months, 28.5% of the patients walked outdoors. Additionally, after 4 months about 30% of the patients were still suffering from pain after hip fracture surgery and still using analgesics. There was a reduction in length of stay between 2011 and 2013. As a part of the national quality register the questions from EQ5D were used before surgery and after 4 months. Before discharge from hospital there were less registered complications in 2012 and 2013 compared with 2011. CONCLUSIONS: The national hip fracture quality register allows healthcare staff to analyse nursing outcomes and to highlight some fundamental aspects of care. IMPLICATIONS FOR PRACTICE: Greater awareness, among hospital staff, of risk factors for complications in hip fracture patients may lead to improved patient care. Through registration in a quality register and working with the results we as Registered Nurses can ensure quality health care for older adults. PMID- 26681170 TI - Successful use of minimal incision superficialization technique for arteriovenous fistula maturation. AB - BACKGROUND: Successful cannulation is an important prerequisite for a functional arteriovenous fistula (AVF). Reasons for unsuccessful cannulation of an AVF are multifactorial and poorly evaluated. In our experience, a needle access segment (NAS) with a length of 10 cm, <5 mm deep from the skin surface, and >6 mm diameter assessed objectively using duplex Doppler ultrasound (DDUS) imaging, in a fistula with brachial artery flow >500 mL/min, permits consistent cannulation. This report provides observational data on the NAS of the outflow veins after fistula creation and a detailed long-term outcome on AVFs that needed superficialization of the NAS using minimal incision superficialization technique (MIST) to make them suitable for cannulation. This report is based on prospectively collected data with a longitudinal follow-up in a large patient cohort. METHODS: A prospective database was used to analyze consecutive patients undergoing AVF until the study end point. All patients underwent a protocol-based maturation evaluation using color DDUS imaging. Unsuitable NAS were surgically corrected using superficialization (by MIST or lipectomy) of deeply situated veins or NAS reconstruction. RESULTS: Between February 1, 2007, and May 31, 2013, 617 new AVF surgeries were performed. Outflow vein superficialization (MIST or lipectomy) or NAS reconstruction was necessary in 226 of 585 procedures (38.6%) included in this analysis. Of these, 162 (72%) were performed using MIST, 50 (22%) with a single long incision, and 14 (6%) using lipectomy technique. Technical success for MIST was 100%, and only two fistulae failed to mature. The vein depth of 9.2 +/- 3.2 mm during initial vessel mapping was similar to the pre MIST depth of 9.1 +/- 3.8 mm. Depth of NAS improved to 3.1 +/- 1.0 mm after MIST. The secondary patency after MIST at 6, 12, 24, 48, and 60 months was 98%, 93.3%, 88.1%, 83.3%, and 80.9%. During the 400.8 post-MIST functional fistula-years, only 0.63 procedures per year were required to maintain AVF patency. CONCLUSIONS: Our data suggest that maturation of AVFs using objective criteria based on DDUS provides an opportunity to identify NAS problems in outflow veins before cannulation. Most of the of the AVF outflow veins (71.7%) could be transposed or superficialized using MIST, with excellent long-term outcomes. PMID- 26681171 TI - A distinct variant of papillary thyroid carcinoma indicating familial adenomatous polyposis (FAP): a case report and brief review. AB - BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. CASE PRESENTATION: A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. CONCLUSION: Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms. PMID- 26681172 TI - Novel Insights into 46,XY Disorders of Sex Development due to NR5A1 Gene Mutation. AB - The differential diagnosis of 46,XY disorders of sex development (DSD) is based on the distinction between forms of gonadal dysgenesis and disorders of androgen biosynthesis and action. However, clinical and endocrine evaluations are often not conclusive. Here, we describe an adolescent female with hirsutism and hyperandrogenization at puberty. Her karyotype was 46,XY, and clinical investigation demonstrated clitoromegaly, but no uterine remnants were detected. Histology of the gonads revealed a testicular structure with a Sertoli-cell-only pattern. Endocrine evaluation showed hypergonadotropic hypogonadism, and the Sertoli cell markers inhibin B and anti-Mullerian hormone were also low. Several molecular genetic studies were initiated. While analyses of the androgen receptor gene, the SRD5A2 gene and HSD17B3 gene were uninformative, a novel p.L230R mutation was found in the NR5A1 gene. A mutant construct proved a severe dysfunction of this variant in functional analysis after recreation and transfection into HeLa cells. We conclude that the NR5A1 p.L230R mutation most likely leads to a spatial and time-dependent Leydig cell and Sertoli cell dysfunction during development not causing the classical gonadal dysgenesis phenotype. This case demonstrates that the current classification should be updated to encompass the overlapping phenotypes of some genetic conditions within 46,XY DSD. PMID- 26681173 TI - The State of Interventions for Sibling Conflict and Aggression: A Systematic Review. AB - Sibling conflict and aggression is often a pervasive part of family life that parents want help managing and can have negative effects on children's well being. The purpose of this systematic review is to evaluate current research regarding programs to reduce sibling conflict and aggression and promote positive sibling relationships. Online databases, reference lists, and Google Scholar were searched using key words and inclusion/exclusion criteria were applied. The search located five unique studies of programs focused on school-aged children. Heterogeneity of the studies precluded meta-analysis, but characteristics of the studies were systematically described. Three interventions were aimed at directly improving children's social skills and two interventions trained parents on mediation techniques to use during sibling conflicts. Overall, of the four studies that included assessment of children's social skills, the results were positive. Two of the three studies that evaluated sibling relationship quality demonstrated improved sibling interactions compared with the control group. With further research and evidentiary support, these programs have promise to modify sibling behaviors as part of current parenting education programs or as a stand alone program to address sibling conflict and aggression. PMID- 26681174 TI - Excision and Fat Grafting of Nasal Tip Dermoid Cysts Through an Open Rhinoplasty Approach. AB - Nasal tip dermoid cysts that are present in pediatric patients can be complicated by mass effect causing compression and distortion of underlying cartilaginous structures. The purpose of this report is to describe a single surgeon's technique and results of nasal tip dermoid cyst excision in pediatric patients through an open rhinoplasty approach followed by tip reconstruction and immediate fat grafting. A series of 3 pediatric patients presented with 1 to 1.5 cm nasal tip dermoid cysts that were causing distortion of the lower lateral cartilages. All 3 underwent excision of the cyst through an open rhinoplasty approach. The nasal tip was reconstructed with interdomal sutures and immediate fat grafting. Fat grafts were harvested from the abdominal wall and implanted in the nasal tip. The grafts filled the resulting dead space and were secured with the fibrin glue. The soft tissue was redraped, and the skin was closed. The final postoperative result, 2 years after surgical intervention, included a well-proportioned and appropriately shaped nasal tip without obvious incisional scars in all patients. The skin overlying the previously excised dermoid cyst was supple and healthy. Excision of nasal tip dermoid cysts in pediatric patients can be approached through an open rhinoplasty approach, tip reconstruction, and immediate fat grafting. This approach can provide assistance in correcting contour deformities and may help preserve an at-risk soft-tissue envelope. PMID- 26681175 TI - Apoptosis-like death was involved in freeze-drying-preserved fungus Mucor rouxii and can be inhibited by L-proline. AB - Freeze-drying is one of the most effective methods to preserve fungi for an extended period. However, it is associated with a loss of viability and shortened storage time in some fungi. This study evaluated the stresses that led to the death of freeze-dried Mucor rouxii by using cell apoptotic methods. The results showed there were apoptosis-inducing stresses, such as the generation of obvious intracellular reactive oxygen species (ROS) and metacaspase activation. Moreover, nuclear condensation and a delayed cell death peak were determined after rehydration and 24 h incubation in freeze-dried M. rouxii via a propidium iodide (PI) assay, which is similar to the phenomenon of cryopreservation-induced delayed-onset cell death (CIDOCD). Then, several protective agents were tested to decrease the apoptosis-inducing stresses and to improve the viability. Finally, it was found that 1.6 mM L-proline can effectively decrease the nuclear condensation rate and increase the survival rate in freeze-dried M. rouxii. IN CONCLUSION: (1) apoptosis-inducing factors occur in freeze-dried M. rouxii. (2) ROS and activated metacaspases lead to death in freeze-dried M. rouxii. (3)L proline increases the survival rate of freeze-dried M. rouxii. PMID- 26681176 TI - Meiotic maturation and developmental capability of ovine oocytes at germinal vesicle stage following vitrification using different cryodevices. AB - In order to assess effects of vitrification on ovine oocytes at the germinal vesicle (GV) stage, the conventional plastic straw (CS), the open-pulled straw (OPS), and Cryoloop were used to vitrify ovine oocytes. Oocytes were randomly divided into five groups: (1) Control; (2) Oocytes exposed to vitrification and dilution solutions without any cryopreservation (toxicity); (3) Oocytes vitrified using CS (CS); (4) Oocytes vitrified using OPS (OPS), and (5) Oocytes vitrified using Cryoloop (Cryoloop). The viability, cumulus cell expansion, nuclear maturation after in vitro maturation (IVM), and developmental capability of vitrified oocytes following parthenogenetic activation (PA) or in vitro fertilization (IVF) were assessed. The pretreatment in the vitrification and dilution solutions without any freezing or thawing did not adversely influence oocytes. The viability of vitrified oocytes were significantly declined compared to unfrozen oocytes (P < 0.05). The viability of oocytes vitrified using open pulled straws or Cryoloop was significantly higher than that in the CS group (P < 0.05). After IVM, the percentage of oocytes reaching to the metaphase II (MII) stage was significantly higher with Cryoloop and OPS following by CS. However, the in vitro maturing percentage of vitrified oocytes was significantly less than that of unfrozen oocytes (P < 0.05). After PA, the developmental capability of vitrified oocytes was significantly decreased compared to unfrozen oocytes. The cleavage rate of oocytes vitrified using conventional plastic straws was significantly less than those of the other freezing groups (P < 0.05). The cleaving capability of oocytes vitrified using Cryoloop was significantly increased compared to the OPS group. However, there was no significant difference existing amongst the freezing groups as concerning the blastocyst rate. Following IVF, the developmental capability of vitrified oocytes was severely damaged compared to that of unfrozen oocytes. The cleavage rate of oocytes vitrified with Cryoloop was similar to that of oocytes vitrified with open-pulled straws. However, the cleavage rate of vitrified oocytes in the CS group was significantly less than that in the OPS or Cryoloop group (P < 0.05). None of oocytes vitrified using conventional plastic straw developed to the blastocyst stage following IVF. There was no significant difference existing between OPS and Cryoloop with respect to the blastocyst rate. After staining with cFDA and PI, cumulus cells surrounding oocytes were partly damaged by vitrification and thawing while the membrane of vitrified oocyte still remained intact. In conclusion, vitrification can seriously damage ovine immature oocytes and cumulus cells surrounding oocytes, which may subsequently affect their developmental capability. Finally, this study further proves that increasing the freezing and thawing velocity benefits survival of vitrified immature oocytes. PMID- 26681177 TI - Strategies to promote family-professional collaboration: two case reports. AB - PURPOSE: Although research supports family-professional collaboration, challenges to implementation have been reported. The case reports describe the implementation of a 4-step practice model that incorporates specific strategies to facilitate family-professional collaboration. METHOD: The participants were two mothers of children with physical disabilities and two physical therapists. Therapists received instruction in the strategies for collaboration including client-centred interview, visualising a preferred future, scaling questions, and family routine and activity matrix. The intervention was implemented during 6 weekly sessions. The 2nd and 5th sessions were videotaped to analyse the interactions between the parent and therapist using Response Class Matrix. Telephone interviews were conducted to explore participants' experiences. RESULTS: Therapists were able to implement all strategies following 6 h of instruction. Analysis of the videotapes indicated that mother-therapist interactions were characterised by sharing information and open communication in a mutually supportive manner. Interviews with the mothers and therapists indicated that the therapists engaged the mothers in the intervention process and tailored interventions to child and family needs. The scaling questions were difficult to implement (therapists) and answer (parents). CONCLUSION: The findings suggest that the strategies can be used by therapists to promote collaboration and involve parents in setting goals and the intervention process. Implications for Rehabilitation Strategies to promote parent-therapist collaboration include client-centred interview, visualising a preferred future, scaling questions, and family routine and activity matrix. Therapists with no previous instruction or training on family-centred services successfully implemented the strategies following 6 h of instruction. Interactions between two parent-physical therapist dyads were characterised by sharing information and open communication in a mutually supportive manner following therapist instruction in strategies for parent-therapist collaboration. PMID- 26681178 TI - Complex Rearrangement Involving Three Chromosomes, Four Breakpoints and a 2.7-Mb Deletion in the 18q Segment Observed in a Girl with Mild Learning Difficulties. AB - Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving 3 or more cytogenetic break events on 2 or more different chromosomes. Here, we report a 7-year-old girl referred to our unit because of mild dysmorphic facial features, mild learning difficulties together with very mild mental retardation. Standard cytogenetic banding analysis revealed a de novo CCR involving chromosomes 1, 2 and 18. Further molecular investigation with aCGH revealed a cryptic interstitial deletion of 2.7 Mb in 18q22.1, which does not elicit a significant clinical phenotype. FISH was performed to confirm both molecular and cytogenetic results. PMID- 26681180 TI - Fat ViP MRI: Virtual Phantom Magnetic Resonance Imaging of water-fat systems. AB - OBJECT: Virtual Phantom Magnetic Resonance Imaging (ViP MRI) is a method to generate reference signals on MR images, using external radiofrequency (RF) signals. The aim of this study was to assess the feasibility of ViP MRI to generate complex-data images of phantoms mimicking water-fat systems. MATERIALS AND METHODS: Various numerical phantoms with a given fat fraction, T2* and field map were designed. The k-space of numerical phantoms was converted into RF signals to generate virtual phantoms. MRI experiments were performed at 4.7T using a multi-gradient-echo sequence on virtual and physical phantoms. The data acquisition of virtual and physical phantoms was simultaneous. Decomposition of the water and fat signals was performed using a complex-based water-fat separation algorithm. RESULTS: Overall, a good agreement was observed between the fat fraction, T2* and phase map values of the virtual and numerical phantoms. In particular, fat fractions of 10.5+/-0.1 (vs 10% of the numerical phantom), 20.3+/ 0.1 (vs 20%) and 30.4+/-0.1 (vs 30%) were obtained in virtual phantoms. CONCLUSION: The ViP MRI method allows for generating imaging phantoms that i) mimic water-fat systems and ii) can be analyzed with water-fat separation algorithms based on complex data. PMID- 26681179 TI - A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs. AB - Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and availability of the prediction programs. Here we report a large scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy...) are applied. We found that i) the tools have been greatly improved over the years; ii) some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii) RNA binding and DNA binding appear to follow similar driving forces and iv) dataset bias may exist in some methods. PMID- 26681181 TI - Genome-Wide Dissection of the MicroRNA Expression Profile in Rice Embryo during Early Stages of Seed Germination. AB - The first 24 hours after imbibition (HAI) is pivotal for rice seed germination, during which embryo cells switch from a quiescent state to a metabolically active state rapidly. MicroRNAs (miRNAs) have increasingly been shown to play important roles in rice development. Nevertheless, limited knowledge about miRNA regulation has been obtained in the early stages of rice seed germination. In this study, the small RNAs (sRNAs) from embryos of 0, 12, and 24 HAI rice seeds were sequenced to investigate the composition and expression patterns of miRNAs. The bioinformatics analysis identified 289 miRNA loci, including 59 known and 230 novel miRNAs, and 35 selected miRNAs were confirmed by stem-loop real-time RT PCR. Expression analysis revealed that the dry and imbibed seeds have unique miRNA expression patterns compared with other tissues, particularly for the dry seeds. Using three methods, Mireap, psRNATarget and degradome analyses, 1197 potential target genes of identified miRNAs involved in various molecular functions were predicted. Among these target genes, 39 had significantly negative correlations with their corresponding miRNAs as inferred from published transcriptome data, and 6 inversely expressed miRNA-target pairs were confirmed by 5'-RACE assay. Our work provides an inventory of miRNA expression profiles and miRNA-target interactions in rice embryos, and lays a foundation for further studies of miRNA-mediated regulation in initial seed germination. PMID- 26681182 TI - Evaluation of nutrients and major ions in streams-implications of different timescale procedures. AB - Small watersheds are characterized by a high degree of sensitivity to changes observed in their environment, making them important sampling and management units. Due to this high sensitivity, several studies have shown that intensive collecting may be more effective in these systems compared to other timescale procedures. The aim of this study was to evaluate the concentration of organic and inorganic nutrients and major ions dissolved in two small watersheds with different land uses to determine whether there are differences between these watersheds with different levels of impact and to identify the most appropriate timescale procedure for the variables under analysis. Therefore, monthly, daily, and hourly samples were taken in the two streams in the northeast of Brazil. One of the streams is located in an undisturbed area (environmental protected area) (S1) and one in a disturbed area (S2). The results showed significant differences for conductivity, temperature, pH, dissolved oxygen (%), sodium (Na(+)), and chloride (Cl(-)) ions and higher values presented in the anthropogenic stream. Dissolved inorganic nitrogen (DIN) in S2 mainly comprised ammonium (NH4 (+)), while nitrate (NO3 (-)) predominated in S1. The considerable increase in the concentration of NO3 (-) and dilution of Na(+) and Cl(-) after rain in April in S1 shows how precipitation may change the chemical composition of the water in a 1-day period. No changes were observed in the concentrations of major ions and nutrients that could be related to the cyclical variation of the hours during the day in both small watersheds. Daily collections allow better monitoring of the dynamics of streams and greater robustness of the data. PMID- 26681183 TI - Optimal design of monitoring networks for multiple groundwater quality parameters using a Kalman filter: application to the Irapuato-Valle aquifer. AB - A new method for the optimal design of groundwater quality monitoring networks is introduced in this paper. Various indicator parameters were considered simultaneously and tested for the Irapuato-Valle aquifer in Mexico. The steps followed in the design were (1) establishment of the monitoring network objectives, (2) definition of a groundwater quality conceptual model for the study area, (3) selection of the parameters to be sampled, and (4) selection of a monitoring network by choosing the well positions that minimize the estimate error variance of the selected indicator parameters. Equal weight for each parameter was given to most of the aquifer positions and a higher weight to priority zones. The objective for the monitoring network in the specific application was to obtain a general reconnaissance of the water quality, including water types, water origin, and first indications of contamination. Water quality indicator parameters were chosen in accordance with this objective, and for the selection of the optimal monitoring sites, it was sought to obtain a low-uncertainty estimate of these parameters for the entire aquifer and with more certainty in priority zones. The optimal monitoring network was selected using a combination of geostatistical methods, a Kalman filter and a heuristic optimization method. Results show that when monitoring the 69 locations with higher priority order (the optimal monitoring network), the joint average standard error in the study area for all the groundwater quality parameters was approximately 90 % of the obtained with the 140 available sampling locations (the set of pilot wells). This demonstrates that an optimal design can help to reduce monitoring costs, by avoiding redundancy in data acquisition. PMID- 26681184 TI - Metal Concentrations in Two Commercial Tuna Species from an Active Volcanic Region in the Mid-Atlantic Ocean. AB - Concentrations of cadmium (Cd), mercury (Hg), and lead [Pb (ug g(-1) wet weight)] were determined in liver and muscle samples of 15 bigeye (Thunnus obesus) and 15 skipjack tunas (Katsuwonus pelamis) caught over an active volcanic region in the Mid-Atlantic Ocean (Azores, Portugal) and evaluated regarding consumption safety. None of the muscle samples (edible part) exceeded the European Union (EU) maximum limits (MLs) for Hg and Pb. Cd concentrations in muscle were much greater than EU MLs with 53 and 26 % of the bigeye tuna and skipjack tuna, respectively, in exceedance of the limits. Results obtained in this work, together with other studies in the same region, support the existence of an important volcanic source of Cd in waters of the Mid-Atlantic region, which should be carefully monitored given the importance of many commercial marine species for human consumption, mainly in Europe. PMID- 26681185 TI - Provisional pin fixation: An efficient alternative to manual maintenance of reduction in nailing of intertrochanteric fractures. AB - INTRODUCTION: During nailing of intertrochanteric fractures, there is always a risk of reduction loss despite achieving an acceptable reduction status after a percutaneous procedure. Most surgeons usually attempted to maintain the reduction with a manual endeavor. However, we experienced varying amounts of intraoperative reduction loss and had to perform readjustments several times. These struggles motivated us to attempt provisional pin fixation as an alternative method. The purpose of this study was to analyze the factors affecting intraoperative reduction loss, especially in comparison between two methods. MATERIALS AND METHODS: Sixty-eight patients with intertrochanteric fractures were included. They were divided into two groups based on the method, by retrospective analysis of the intraoperative c-arm image. In the manual maintenance group, an assistant maintained the instruments during the procedure. In the provisional pin fixation group, the reduction was temporaryily held by a 3.2mm guide pin fixation across the fracture. A displacement of more than one cortical thickness in any plane or angular deformity during any point in the procedure after acceptable reduction was judged as an intraoperative reduction loss. Multivariate logistic regression was used for statistical analysis. RESULTS: The number of cases with intraoperative reduction loss was 18 (18 of 38, 46.1%) in the manual maintenance group and 6 (6 of 30, 20.0%) in the provisional pin fixation group. The odds ratio of intraoperative reduction loss in the manual maintenance group was 5.182 (95% confidence interval, 1.455-18.452) compared with the provisional pin fixation group as the reference. CONCLUSIONS: As a reasonable approach for maintaining reduction, provisional pin fixation can significantly decrease intraoperative reduction loss after percutaneous reduction of intertrochanteric fractures during nailing. PMID- 26681186 TI - Quinazolines as Apoptosis Inducers and Inhibitors: A Review of Patent Literature. AB - Quinazoline scaffold has been successfully utilized for development of various inhibitors of tubulin, epidermal growth factor receptor (EGFR), polo like kinases (PLKs), Hedgehog-Gli signaling pathway and protein kinase B (PKB) /Akt pathway. Compounds based on quinazolines have shown efficacies in uM to nM range in various cancer cell lines and thus could be useful scaffolds for development of both apoptosis inducers as well as inhibitors. This compilation is based on various patents published till 2015 and divides the quinazolines in two main categories: Quinazolines as apoptosis inducers and as apoptosis inhibitors. These two main categories are further sub-categorized based on the use/pharmacological indications for these classes of patented compounds. This review will act as a tool for the researchers working on exploring the anticancer potential of quinazoline as a privileged heterocyclic. The promising anticancer profile of some of the quinazoline based compounds clearly highlights the clinical potential of this heterocycle. PMID- 26681188 TI - The ageing of Africa. PMID- 26681187 TI - Is Mixed Apnea Associated with Non-Rapid Eye Movement Sleep a Reversible Compensatory Sign of Heart Failure? AB - BACKGROUND: Sleep-disordered breathing is common in heart failure (HF), and prolonged circulation time and diminished pulmonary volume are considered the main possible causes of sleep apnea in these patients. However, the impact and interrelation between sleep apnea and HF development are unclear. We report the case of a patient with complete elimination of non-rapid-eye-movement (NREM) sleep-associated mixed apnea in HF after heart transplantation. CASE REPORT: After unsuccessful 12-month conventional treatment with abrupt exacerbation of biventricular HF IV class (according to New York Heart Association Functional Classification), a 26-year-old man was admitted to the hospital. Based on a comprehensive examination including endomyocardial biopsy, dilated cardiomyopathy was diagnosed. Heart transplantation was considered the only possible treatment strategy. Polysomnography showed severe NREM sleep-associated mixed sleep apnea [apnea-hypopnea index 43/h, in rapid eye movement (REM) sleep 3.7/h, in NREM sleep 56.4/h, mean SatO2 93.9%], and periodic breathing. One-month post transplantation polysomnography did not show sleep-disordered breathing (apnea hypopnea index 1.0/h; in REM sleep - 2.8/h, in NREM sleep 0.5/h, mean SatO2 97.5%). The patient was discharged from the hospital in improved condition. CONCLUSIONS: NREM sleep-associated mixed apnea occurring in severe systolic HF due to dilated cardiomyopathy might be reversible in case of successful HF treatment. We suggest that mixed sleep apnea strongly associated with NREM sleep occurs in HF, when the brain centers regulating ventilation are intact, and successful HF compensation might be highly effective regarding sleep-breathing disorders without non-invasive ventilation. This is important to know, especially with regard to the recently published data of potentially unfavorable effects of adaptive servoventilation in systolic HF, and the lack of other treatment options. PMID- 26681189 TI - Adenoviral Vector-Mediated Delivery of p21WAF1/CIP1 Prevents Retinal Neovascularization in an Oxygen-Induced Retinopathy Model. AB - OBJECTIVE: To evaluate the inhibitory effect(s) of adenovirus (Ad) vector mediated delivery of p21WAF1/CIP1 (Ad-p21) on retinal neovascularization (RNV) in an animal model of oxygen-induced retinopathy (OIR). METHODS: RNV was determined by examination of retinal fiat mounts and sections postnatal (P) day-17 (P17). Non-perfused retinal areas were analyzed using Image-Pro plus 6.0 software. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to measure mRNA and protein expression of p21 and cyclin dependent kinase (CDK) 2. RESULTS: Compared with phosphate buffer saline (PBS) and Ad-NC group mice, non-perfused retinal areas, neovascularization, and number of endothelial cell nuclei breaking through the internal limiting membrane (ILM) in Ad-p21 group mice were significantly reduced. There were fewer non-perfused retinal areas in Ad-p21 mice than in either PBS or Ad-NC group mice, the differences being significant (F = 101.634; p < 0.05). Levels of p21 mRNA and protein in the Ad-p21 group had increased significantly compared with the other three groups (F = 839.664, 509.817; p < 0.05). Levels of CDK2 mRNA and protein in the Ad-p21 group decreased significantly (F = 301.858, 592.882; p < 0.05). CONCLUSIONS: Ad-p21 inhibits RNV in OIR. A potential underlying mechanism for this may be that overexpression of p21 arrests the cell cycle at the G1- to S phase transition via inhibition of CDK2 activity. PMID- 26681192 TI - Erratum to: Angiomyolipoma being surgically excised for presumed kidney carcinoma. PMID- 26681191 TI - Comparison of the caries-protective effect of fluoride varnish with treatment as usual in nursery school attendees receiving preventive oral health support through the Childsmile oral health improvement programme - the Protecting Teeth@3 Study: a randomised controlled trial. AB - BACKGROUND: The Scottish Government set out its policy on addressing the poor oral health of Scottish children in 2005. This led to the establishment of Childsmile, a national programme designed to improve the oral health of children in Scotland. One element of the programme promotes daily tooth brushing in all nurseries in Scotland (Childsmile Core). A second targeted component (Childsmile Nursery) offers twice-yearly application of fluoride varnish to children attending nurseries in deprived areas. Studies suggest that fluoride varnish application can reduce caries in both adult and child populations. This trial aims to explore the effectiveness and cost-effectiveness of additional preventive value fluoride varnish application compared to Childsmile Core. METHODS/DESIGN: The Protecting Teeth@3 Study is an ongoing 2 year parallel group randomised treatment as usual controlled trial. Three-year-old children attending the ante pre-school year are randomised (1:1) to the intervention arm (fluoride varnish & treatment as usual) or the control arm (treatment as usual). Children in the intervention arm will have Duraphat(r) fluoride varnish painted on the primary tooth surfaces and will continue to receive treatment as usual: the core Childsmile Nursery intervention. Children in the treatment as usual arm will receive the same series of contacts, without the application of varnish and will also continue with the Childsmile Core intervention. Interventions are undertaken by Childsmile trained extended duty dental nurses at six-monthly intervals. Participants receive a baseline dental inspection in nursery and an endpoint inspection in Primary 1 at the age of 5 years old. We will use primary and secondary outcome measures to compare the effectiveness of Duraphat(r) fluoride varnish plus treatment as usual with treatment as usual only in preventing any further dental decay. We will also undertake a full economic evaluation of the trial. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov. Number: NCT01674933 (24 August 2012). PMID- 26681190 TI - Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population. AB - OBJECTIVES: Individual variations in the capacity of DNA repair machinery to relieve benzene-induced DNA damage may be the key to developing chronic benzene poisoning (CBP), an increasingly prevalent occupational disease in China. ERCC1 (Excision repair cross complementation group 1) is located on chromosome 19q13.2 3 and participates in the crucial steps of Nucleotide Excision Repair (NER); moreover, we determined that one of its polymorphisms, ERCC1 rs11615, is a biomarker for CBP susceptibility in our previous report. Our aim is to further explore the deeper association between some genetic variations related to ERCC1 polymorphisms and CBP risk. METHODS: Nine single nucleotide polymorphisms (SNPs) of XRCC1 (X-ray repair cross-complementing 1), CD3EAP (CD3e molecule, epsilon associated protein), PPP1R13L (protein phosphatase 1, regulatory subunit 13 like), XPB (Xeroderma pigmentosum group B), XPC (Xeroderma pigmentosum group C) and XPF (Xeroderma pigmentosum group F) were genotyped by the Snapshot and TaqMan MGB(r) probe techniques, in a study involving 102 CBP patients and 204 controls. The potential interactions between these SNPs and lifestyle factors, such as smoking and drinking, were assessed using a stratified analysis. RESULTS: An XRCC1 allele, rs25487, was related to a higher risk of CBP (P<0.001) even after stratifying for potential confounders. Carriers of the TT genotype of XRCC1 rs1799782 who were alcohol drinkers (OR = 8.000; 95% CI: 1.316-48.645; P = 0.022), male (OR = 9.333; 95% CI: 1.593-54.672; P = 0.019), and had an exposure of <=12 years (OR = 2.612; 95% CI: 1.048-6.510; P = 0.035) had an increased risk of CBP. However, the T allele in PPP1R13L rs1005165 (P<0.05) and the GA allele in CD3EAP rs967591 (OR = 0.162; 95% CI: 0039~0.666; P = 0.037) decreased the risk of CBP in men. The haplotype analysis of XRCC1 indicated that XRCC1 rs25487A, rs25489G and rs1799782T (OR = 15.469; 95% CI: 5.536-43.225; P<0.001) were associated with a high risk of CBP. CONCLUSIONS: The findings showed that the rs25487 and rs1799782 polymorphisms of XRCC1 may contribute to an individual's susceptibility to CBP and may be used as valid biomarkers. Overall, the genes on chromosome 19q13.2-3 may have a special significance in the development of CBP in occupationally exposed Chinese populations. PMID- 26681194 TI - Neoplasm arising from the descended testis in a unilateral cryptorchid child: decisions and dilemmas. PMID- 26681193 TI - Does the presence of vesicoureteral reflux affect in vitro uropathogenic E. coli growth rate in urine? AB - BACKGROUND: Uroepithelial molecules like uroplakins are involved both in the development of urinary tract and in colonization, attachment and invasion of uropathogenic Escherichia coli (UPEC). Uroplakin disorders are also associated with vesicoureteral reflux (VUR). We hypothesized that urine contents, as well as urinary flow, may be altered in VUR, and aimed to determine whether in vitro UPEC growth is increased in urine from the refluxing systems. METHODS: Children evaluated by voiding cystourethrography for UTI were enrolled. Groups 1 and 2 included children with and without VUR, respectively. Sterile urine samples were obtained from all patients, and 2 * 10(2) cfu/mL UPEC suspension was inoculated into these samples. After incubation for 24 h, colony counts were assessed. Both groups were compared for UPEC growth and colony counts. RESULTS: Forty-two urine samples were included (21 in each group). UPEC was cultured in 9 (43 %) and 3 (14 %) samples in Groups 1 and 2, respectively (p = 0.040, OR 4.5). Colony counts were similar in both groups (log x; 2.36 +/- 0.25 vs. 2.37 +/- 0.12, p = 0.923). CONCLUSION: Inoculation of 2 * 10(2) cfu UPEC resulted in growth in almost half of the urine samples from refluxing systems, while UPEC growth was inhibited in most urine samples from non-refluxing systems suggesting that urine contents in refluxing units change in such a way that UPEC growth is facilitated. PMID- 26681195 TI - FDG PET/CT allowing detection and follow-up of tumor cell transplantation. AB - After detection of small cell lung cancer in a 67-year-old patient who had donated a kidney 7 months earlier, the graft recipient underwent FDG-PET/CT to determine the presence/absence of tumor cell transmission. It showed abnormal increased uptake of the renal graft, associated with hypermetabolic lymph nodes and hepatic, pulmonary and bone lesions. Emergency graft resection was performed 5 days after PET/CT, permitting immunosuppressive therapy withdrawal. Pathologic examination of the kidney showed parenchymal infiltration by tumor cells compatible with small cell lung cancer. Thereafter, pathologists proved that the recipient's and donor's tumor cells matched using microsatellite markers. FDG PET/CT was performed in the follow-up and showed progression in the donor despite chemotherapy and radiotherapy. He died a few months later. However, FDG-PET/CT showed a complete metabolic response after only 3 courses of chemotherapy in the recipient. PMID- 26681197 TI - Myocardial infarction, symptomatic third degree atrioventricular block and pulmonary embolism caused by thalidomide: a case report. AB - BACKGROUND: Thalidomide has been reported to cause numerous thromboembolic events. Deep vein thrombosis and pulmonary embolism are more common. It can also cause bradycardia and even total atrioventricular block. Rarely, it causes coronary artery spasm and even myocardial infarction. But almost simultaneous onset of myocardial infarction, third degree atrioventricular block and pulmonary embolism in one patient has not been reported so far. CASE PRESENTATION: A 53 year old man presented because of chest pain, nausea and then syncope for several minutes. Previous medical history included neurodermitis for which thalidomide was given and hypercholesterolemia with simvastatin taking. The patient didn't exhibit any other established risk factors for coronary artery disease. Electrocardiography showed sinus rhythm with third degree atrioventricular block and complete right bundle branch block, and precordial leads ST segment elevation. The diagnosis of acute coronary syndrome was suspected, but further coronary angiography demonstrated no flow-limiting lesions in coronary arteries, and temporary pacemaker was implanted. After admission, low SpO2 and elevated D dimer level was mentioned. Further computed tomography pulmonary angiography revealed pulmonary embolism. Thalidomide was thought to be the cause of hypercoagulability and coronary spasm, so it was ceased immediately. Therapeutic low molecule weight heparin was initiated and then switched to warfarin with appropriate INR, and nifedipine was described for coronary spasm. The patient's symptoms completely relived and SpO2 recovered, and atrioventricular block had disappeared during hospitalization with pacemaker removed. CONCLUSION: This is the very first case in which myocardial infarction, third degree atrioventricular block and pulmonary embolism almost simultaneously developed. We should be ware that anti-thrombotic prophylaxis, which needs further investigation for optimal drug and dosage, may be beneficial in thalidomide therapy. And it is also important to monitor patients taking thalidomide for signs and symptoms of bradycardia or higher degree atrioventricular block. PMID- 26681196 TI - Signature of cytokines and angiogenic factors (CAFs) defines a clinically distinct subgroup of gastric cancer. AB - BACKGROUND: Little is known about cytokine and angiogenic factors (CAFs) in gastric cancer (GC) in terms of tumor classification and prognostic value. Here, we aimed to correlate CAF signature with overall survival (OS) in GC. METHODS: We measured pretreatment serum levels of 52 kinds of CAFs in 68 GC patients who were treated with fluoropyrimidine and platinum combination chemotherapy using multiplex bead immunoassays and enzyme-linked immunosorbent assay. We evaluated correlations between CAF levels and pathological features and OS. RESULTS: Three distinct patient groups were identified: one with high levels of proangiogenic factors, another with high levels of proinflammatory factors, and the other with high levels of both factors. Eleven CAFs [interleukin (IL)-2 receptor-alpha, growth-regulated alpha protein, hepatocyte growth factor, macrophage colony stimulating factor, stromal cell-derived factor, IL-6, IL-8, IL-10, interferon gamma, vascular endothelial growth factor, and osteopontin] were independently correlated with poor OS. Clustering analysis of these 11 CAFs revealed distinct high and low 11-CAF signature groups. High 11-CAF signature was associated with shorter OS (10.1 vs. 17.9 months, p = 0.026) along with poor performance status, and the presence of signet ring cell components in multivariate analysis of OS (HR 1.76, p = 0.029). The patients' traditional clinicopathological characteristics were not significantly different between the high and low 11-CAF signature groups. CONCLUSION: Serum CAF profiling differentiated GC patient groups. A high 11-CAF signature could identify GC patients with a poor prognosis when treated with standard chemotherapy who need urgent new treatment strategies. PMID- 26681198 TI - Fluocinolone acetonide for the treatment of diabetic macular edema. AB - In addition to VEGF inhibitors such as ranibizumab, aflibercept or bevacizumab, clinical and experimental investigations have revealed the great potential of steroids in the treatment of DME. At present two intravitreal steroid inserts are approved for the treatment of DME containing either dexamethasone or fluocinolone acetat (FA) as a pharmacological compound. The non degradable intravitreal FA insert releases 0.2 ug FA per day (Iluvien, Alimera Sciences). Clinical phase III studies have demonstrated the beneficial effect of the FA insert to last up to three years, especially in patients with a prolonged history of DME of at least three years at the initiation of therapy. While the treatment appears to be well tolerated over all, side effects such as cataract formation in nearly all treated phakic patients and raise of intraocular pressure need to be discussed with the patients as potential complications of the treatment. PMID- 26681199 TI - Negative effect of cyclin D1 overexpression on recurrence-free survival in stage II-IIIA lung adenocarcinoma and its expression modulation by vorinostat in vitro. AB - BACKGROUND: This study was aimed at identifying prognostic biomarkers for stage II-IIIA non-small cell lung cancer (NSCLC) according to histology and at investigating the effect of vorinostat on the expression of these biomarkers. METHODS: Expression levels of cyclin D1, cyclin A2, cyclin E, and p16 proteins that are involved in the G1-to-S phase progression of cell cycle were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 372 samples of stage II-IIIA NSCLC. The effect of vorinostat on the expression of these proteins, impacts on cell cycle, and histone modification was explored in lung cancer cells. RESULTS: Abnormal expression of cyclin A2, cyclin D1, cyclin E, and p16 was found in 66, 47, 34, and 51 % of 372 cases, respectively. Amongst the four proteins, only cyclin D1 overexpression was significantly associated with poor recurrence-free survival (adjusted hazard ratio = 1.87; 95 % confidence interval = 1.12 - 2.69, P = 0.02) in adenocarcinoma but not in squamous cell carcinoma (P = 0.44). Vorinostat inhibited cell cycle progression to the S-phase and induced down-regulation of cyclin D1 in vitro. The down-regulation of cyclin D1 by vorinostat was comparable to a siRNA-mediated knockdown of cyclin D1 in A549 cells, but vorinostat in the presence of benzo[a]pyrene showed a differential effect in different lung cancer cell lines. Cyclin D1 down regulation by vorinostat was associated with the accumulation of dimethyl-H3K9 at the promoter of the gene. CONCLUSIONS: The present study suggests that cyclin D1 may be an independent prognostic factor for recurrence-free survival in stage II IIIA adenocarcinoma of lung and its expression may be modulated by vorinostat. PMID- 26681203 TI - Why Does National Income Inequality Make Older People Ill? PMID- 26681200 TI - Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis. AB - Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR 382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR 9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV oncogene transformed epithelial cells. These findings provide a novel understanding of the molecular pathogenesis of chlamydia-associated diseases, which may guide a rational prevention strategy. PMID- 26681202 TI - A cutaneous presentation of a common condition. PMID- 26681204 TI - An all-inorganic polyoxometalate-polyoxocation chemical garden. AB - Herein, we show it is possible to produce wholly inorganic chemical gardens from a cationic polyoxometalate (POM) seed in an anionic POM solution, demonstrating a wholly POM-based chemical garden system that produces architectures over a wide concentration range. Six concentration dependent growth regimes have been discovered and characterized: clouds, membranes, slugs, tubes, jetting and budding. PMID- 26681201 TI - From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. AB - Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34 degrees C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37 degrees C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28 degrees C versus 37 degrees C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37 degrees C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28 degrees C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called "nutritional virulence" strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway. PMID- 26681205 TI - Comparison of immune responses to a killed bivalent whole cell oral cholera vaccine between endemic and less endemic settings. AB - Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity. PMID- 26681206 TI - Contribution of mobile health applications to self-management by consumers: review of published evidence. AB - Objective The aim of the present study was to review the contribution of mobile health applications ('apps') to consumers' self-management of chronic health conditions, and the potential for this practice to inform health policy, procedures and guidelines. Methods A search was performed on the MEDLINE, Cochrane Library, ProQuest and Global Health (Ovid) databases using the search terms 'mobile app*', 'self-care', 'self-monitoring', 'trial', 'intervention*' and various medical conditions. The search was supplemented with manual location of emerging literature and government reports. Mapping review methods identified relevant titles and abstracts, followed by review of content to determine extant research, reports addressing the key questions, and gaps suggesting areas for future research. Available studies were organised by disease state, and presented in a narrative analysis. Results Four studies describing the results of clinical trials were identified from Canada, England, Taiwan and Australia; all but the Australian study used custom-made apps. The available studies examined the effect of apps in health monitoring, reporting positive but not robust findings. Australian public policy and government reports acknowledge and support self management, but do not address the potential contribution of mobile interventions. Conclusions There are limited controlled trials testing the contribution of health apps to consumers' self-management. Further evidence in this field is required to inform health policy and practice relating to self management. What is known about the topic? Australian health policy encourages self-care by health consumers to reduce expenditure in health services. A fundamental component of self-care in chronic health conditions is self monitoring, which can be used to assess progress towards treatment goals, as well as signs and symptoms of disease exacerbation. An abundance of mobile health apps is available for self-monitoring. What does this study add? A limited number of randomised control trials have assessed the clinical impact of health apps for self-monitoring. The body of evidence relating to current and long-term clinical impact is developing. Despite endorsing self-care, Australian health policy does not address the use and potential contribution of mobile health apps to health care. What are the implications? Widespread and sustained use of validated mobile health apps for chronic health conditions should have potential to improve consumer independence, confidence and burden on health services in the longer term. However, a significant body of scientific evidence has not yet been established; this is mirrored in the lack of acknowledgement of health apps in Australian health policy referring to consumers' self-management. PMID- 26681207 TI - Titanium With Nanotopography Induces Osteoblast Differentiation by Regulating Endogenous Bone Morphogenetic Protein Expression and Signaling Pathway. AB - We aimed at evaluating the effect of titanium (Ti) with nanotopography (Nano) on the endogenous expression of BMP-2 and BMP-4 and the relevance of this process to the nanotopography-induced osteoblast differentiation. MC3T3-E1 cells were grown on Nano and machined (Machined) Ti surfaces and the endogenous BMP-2/4 expression and the effect of BMP receptor BMPR1A silencing in both osteoblast differentiation and expression of genes related to TGF-beta/BMP signaling were evaluated. Nano supported higher BMP-2 gene and protein expression and upregulated the osteoblast differentiation compared with Machined Ti surface. The BMPR1A silencing inhibited the osteogenic potential induced by Nano Ti surface as indicated by reduced alkaline phosphatase (ALP), osteocalcin and RUNX2 gene expression, RUNX2 protein expression and ALP activity. In addition, the expression of genes related to TGF-beta/BMP signaling was deeply affected by BMPR1A-silenced cells grown on Nano Ti surface. In conclusion, we have demonstrated for the first time that nanotopography induces osteoblast differentiation, at least in part, by upregulating the endogenous production of BMP-2 and modulating BMP signaling pathway. J. Cell. Biochem. 117: 1718-1726, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26681209 TI - Liquid crystal self-assembly of halloysite nanotubes in ionic liquids: a novel soft nanocomposite ionogel electrolyte with high anisotropic ionic conductivity and thermal stability. AB - We report a novel class of liquid crystalline (LC) nanohybrid ionogels fabricated via self-assembly of natural halloysite nanotubes (HNTs) in ionic liquids (ILs). The obtained ionogels are very stable and nonvolatile and show LC phases over a wide temperature range. Remarkably, the nanocomposite ionogels exhibit high anisotropic ionic conductivity after shear, and their room temperature ionic conductivity can reach 3.8 * 10(-3) S cm(-1) for aligned nanotubes perpendicular to the electrode even when the HNTs content increases to 40 wt%, which is 380 times higher than that obtained for aligned nanotubes parallel to the electrode, which is 1.0 * 10(-5) S cm(-1). Crucially, the obtained LC nanocomposite ionogels have very high thermal stability, which can sustain 400 degrees C thermal treatment. The findings will promote the development of novel nanocomposite ionogel electrolytes with faster ion transport and larger anisotropic conductivity. PMID- 26681208 TI - Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen Resistant Breast Cancer. AB - Almost 70% of breast cancers are estrogen receptor alpha (ERalpha) positive. Tamoxifen, a selective estrogen receptor modulator (SERM), represents the standard of care for many patients; however, 30-50% develop resistance, underlining the need for alternative therapeutics. Paradoxically, agonists at ERalpha such as estradiol (E2) have demonstrated clinical efficacy in patients with heavily treated breast cancer, although side effects in gynecological tissues are unacceptable. A drug that selectively mimics the actions of E2 in breast cancer therapy but minimizes estrogenic effects in other tissues is a novel, therapeutic alternative. We hypothesized that a selective human estrogen receptor partial agonist (ShERPA) at ERalpha would provide such an agent. Novel benzothiophene derivatives with nanomolar potency in breast cancer cell cultures were designed. Several showed partial agonist activity, with potency of 0.8-76 nM, mimicking E2 in inhibiting growth of tamoxifen-resistant breast cancer cell lines. Three ShERPAs were tested and validated in xenograft models of endocrine independent and tamoxifen-resistant breast cancer, and in contrast to E2, ShERPAs did not cause significant uterine growth. PMID- 26681210 TI - Clinical and Economic Outcomes Associated With the Timing of Initiation of Basal Insulin in Patients With Type 2 Diabetes Mellitus Previously Treated With Oral Antidiabetes Drugs. AB - PURPOSE: In patients with type 2 diabetes mellitus (T2DM) not achieving glycemic targets using oral antidiabetes drugs (OADs), studies suggest that timely insulin initiation has clinical benefits. Insulin initiation at the early versus late stage of disease progression has not been explored in detail. This retrospective database analysis investigated clinical and economic outcomes associated with the timing of insulin initiation in patients with T2DM treated with >=1 OAD in a real world US setting. METHODS: This study linked data from the Truven Health MarketScan((r)) Commercial database, Medicare Supplemental database, and Quintiles Electronic Medical Records database. A total of 1830 patients with T2DM were included. Patients were grouped according to their OAD use before basal insulin initiation (1, 2, or >=3 OADs) as a proxy for the timing of insulin initiation. Clinical and economic outcomes were evaluated over 1 year of follow up. FINDINGS: During follow-up the 1 OAD group, compared with the 2 and >=3 OADs groups, had a greater reduction in glycosylated hemoglobin A1c (-1.7% vs -1.0% vs -0.9%, respectively; P < 0.0001), greater achievement of glycemic target (38.2% vs 26.7% vs 19.6%, respectively; P < 0.0001), and a lower incidence of hypoglycemia (2.7% vs 6.6% vs 5.0%, respectively; P = 0.0002), with no difference in total health care costs ($21,167 vs $21,060 vs $20,133, respectively). IMPLICATIONS: This study shows that early insulin initiation (represented by the 1 OAD group) may be clinically beneficial to patients with T2DM not controlled with OADs, without adding to costs. This supports the call for timely initiation of individualized insulin therapy in this population. PMID- 26681212 TI - Regulation network of serum cytokines induced by tuberculosis-specific antigens reveals biomarkers for tuberculosis diagnosis. AB - In this study, we identified potential serum biomarkers for the diagnosis of active tuberculosis (TB) and screening for latent TB infections (LTBIs). Peripheral blood samples from 40 healthy individuals, 40 patients with TB, and 40 LTBI individuals were stimulated with the TB-specific antigens ESAT-6 and CFP-10. Human inflammatory cytokine arrays were used to detect the expression of inflammatory cytokines. Cytokines with significant changes were screened to construct a cytokine regulation network. The levels of the cytokines CCL1 (I 309), CXCL9 (MIG), IL-10, IL-6, CSF2, CSF3, IL-8, IL-1alpha, IL-7, TGF-beta1, CCL2, IL-2, IL-13, and TNFalpha were significantly upregulated in the active TB group. The levels of CCL3, IL-1beta, CCL8, IFNgamma, and CXCL10 were significantly increased in the TB groups compared to those in the healthy control group. sTNF RII was upregulated in the LTBI group. CCL4 and MIP1d were significantly increased in all groups.The upregulated cytokines were mainly found in the IFNgamma and IL-1alpha regulatory networks. Importantly, we found that CXCL10 (IP-10), CCL3, CCL8, and IL-1beta may be more suitable than IFNgamma for active or latent TB infection screening. Furthermore, we found that levels of CCL1 (I-309), CXCL9 (MIG), IL-10, IL-6, CSF2, CSF3, IL-8, IL-1alpha, IL-7, TGF beta1, CCL2, IL-2, and IL-13 after TB antigen stimulation may help distinguish between active and latent TB. PMID- 26681211 TI - WHO Statement on Caesarean Section Rates. PMID- 26681213 TI - Analysis of polymorphisms in the FUT1 and TAP1 genes and their influence on immune performance in Pudong White pigs. AB - FUT1 and TAP1 have been identified as candidate genes that offer resistance against Escherichia coli F18 infection, with the AA genotype in FUT1 and the GG genotype in TAP1 conferring resistance. In order to confirm polymorphisms at FUT1 M307 and TAP1 G729, and evaluate their influence on immunity performance in Pudong White pigs, we performed polymerase chain reaction-restriction fragment length polymorphism analysis, measured immune indices, and compared the results with those observed in Large White pigs. The AA genotype of FUT1 was first discovered in Pudong White pigs and has not been found in other Chinese domestic pig breeds. The frequency of the AA genotype in Pudong White and Large White pigs was 0.018 and 0.052, respectively. The GG genotype of TAP1 was also detected in the two breeds, with a frequency of 0.708 and 0.695, respectively. Chi-square fitness analysis of both genes showed that these loci deviated from Hardy Weinberg equilibrium in the two breeds (P < 0.05). No significant differences were observed in interleukin-6 (IL-6) and IL-10 levels among the three genotypes at FUT1 and TAP1 in the two breeds (P > 0.05). Individuals for all genotypes of TAP1 in both pig breeds had similar TNF-alpha levels (P > 0.05), implying that Pudong White pigs may have the same ability for hepatocyte inflammatory response and B cell differentiation as Large White pigs. These differences have a degree of influence on Pudong White pig's immune ability to resist F18 or other infections. PMID- 26681214 TI - Overexpression of EsMcsu1 from the halophytic plant Eutrema salsugineum promotes abscisic acid biosynthesis and increases drought resistance in alfalfa (Medicago sativa L.). AB - The stress phytohormone abscisic acid (ABA) plays pivotal roles in plants' adaptive responses to adverse environments. Molybdenum cofactor sulfurases influence aldehyde oxidase activity and ABA biosynthesis. In this study, we isolated a novel EsMcsu1 gene encoding a molybdenum cofactor sulfurase from Eutrema salsugineum. EsMcus1 transcriptional patterns varied between organs, and its expression was significantly upregulated by abiotic stress or ABA treatment. Alfalfa plants that overexpressed EsMcsu1 had a higher ABA content than wild-type (WT) plants under drought stress conditions. Furthermore, levels of reactive oxygen species (ROS), ion leakage, and malondialdehyde were lower in the transgenic plants than in the WT plants after drought treatment, suggesting that the transgenic plants experienced less ROS-mediated damage. However, the expression of several stress-responsive genes, antioxidant enzyme activity, and osmolyte (proline and total soluble sugar) levels in the transgenic plants were higher than those in the WT plants after drought treatment. Therefore, EsMcsu1 overexpression improved drought tolerance in alfalfa plants by activating a series of ABA-mediated stress responses. PMID- 26681215 TI - Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis. AB - N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73 1.19) were found; however, the results showed significant heterogeneity (I2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes. In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations. PMID- 26681216 TI - Genetic variability of DNA repair mechanisms in chemotherapy treatment outcome of gastric cancer patients. AB - We investigate whether three common polymorphisms in ERCC1 and ERCC2 are predictor factors for the chemotherapy response, as well as the clinic outcome of patients with gastric cancer. Between May 2011 and May 2013, 263 patients with gastric cancer who were newly diagnosed by histopathology were enrolled in our study. Genotyping of the ERCC1 rs11615 and rs3212986, and ERCC2 rs1799793 polymorphisms were conducted by the polymerase chain reaction-restriction fragment length polymorphism assay. Patients carrying the TT genotype and TT+CT genotype of ERCC1 rs11615 were associated with poorer response to chemotherapy and shorter survival times when compared with the CC genotype. In conclusion, our results suggested that the ERCC1 rs11615 polymorphism in the DNA repair pathways can be used as predictive factors to the clinical outcome of patients with gastric cancer. PMID- 26681217 TI - Diagnostic values of microRNA-31 in peripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients. AB - We investigated the diagnostic values of microRNA-31 in peripheral blood mononuclear cells (PBMCs) for pediatric pulmonary tuberculosis in Chinese patients. Sixty-five children with TB were selected for this study, which was conducted at the Department of Infectious Diseases People's Hospital of Laiwu City between December 2013 and December 2014. Sixty healthy children, selected in parallel, served as the control group. Real-time PCR was used to detect miR-31 expression in PBMCs. Serum levels of IL-6, TNF-alpha, NF-kappaB, and IFN-gamma was detected by ELISA. ROC curve was employed to evaluate the diagnostic value of miR-31 in pediatric TB. Results show that expression of miRNA-31 in pediatric TB patients was significantly lower than that in normal children (0.48 +/- 0.15 vs 1.23 +/- 0.36, P < 0.05). By contrast, serum levels of the innate immune response cytokines, IL-6, TNF-alpha, NF-kappaB, and IFN-gamma, were significantly higher in pediatric TB patients compared with normal children (P < 0.05). Furthermore, miRNA-31 expression was negatively correlated with serum levels of IL-6 (t = 69.91, P < 0.001), TNF-alpha (t = 10.96, P < 0.001), NF-kappaB (t = 39.94, P < 0.001), and IFN -gamma (t = 37.94, P < 0.001). The cut-off threshold of miR-31 for pediatric TB diagnosis is 0.835 with a sensitivity of 98.5% and a specificity of 86.7%. Therefore, miR-31 has the potential to be a diagnostic marker in pediatric TB patients. PMID- 26681218 TI - Distribution of LIM domain kinase 1 in the olfactory bulb, cerebral cortex, hippocampus, and cerebellum of the App/PS+/- mice. AB - LIM domain kinase 1 (LIMK1), an actin-binding kinase, can phosphorylate and inactivate its substrates, and can regulate long-term memory and synaptic plasticity. Both beta-amyloid precursor protein (App) and presenilin (PS) are functional degeneration factors during early neuronal development, and are considered as potential factors that contribute to the development of Alzheimer's disease (AD). However, hardly any information is available about the distribution and expression of LIMK1. Thus, using the App and PS deficient mice, the role of LIMK1 was demonstrated in the absence of App and PS. Our results showed that LIMK1 was present in the nerve fiber layer and external plexiform layer of the olfactory bulb, as well as in the mitral cells and Purkinje cells of the cerebellum in App and PS deficient mice. Additionally, LIMK1 was concentrated in the granule cell layer of the olfactory bulb and cerebellum and LIMK1 positive cells were located in the CA1 region of the hippocampus. Our study indicates that there is a connection between LIMK1 and AD in the mouse model of AD. This might explain neurological problems such as cerebellar ataxia, impaired long-term memory, and impaired synaptic plasticity observed in AD. PMID- 26681219 TI - Analysis of HLA-DQB1 allele polymorphisms in Uyghur women with cervical cancer. AB - In Uyghur women, mortality rates from cervical cancer are amongst the highest in the nation, and genetic susceptibility probably plays a role in the pathogenesis of the disease. We investigated the correlation between polymorphisms of the HLA DQB1 allele and cervical cancer in Xinjiang Uyghur women. Cervix tissue samples from 80 cases of cervical cancer and 80 cases of cervicitis were genotyped using polymerase chain reaction-sequence-based typing (PCR-SBT) for HLA-DQB1. Two hundred and ninety-six alleles were identified among the 160 cases. One hundred and thirty-six alleles were heterozygous and 24 were homozygous. Using frequency calculations and statistical analysis, we found that HLA-DQB1*0325 (OR: 10.60, 1.341-83.81) and HLA-DQB1*0332 (OR: 12.59, 2.909-54.526) were more frequently identified in the cervical cancer group compared with the cervicitis group (P < 0.05). However, HLA-DQB1*0317 (OR: 0.49, 0.304-0.798) and HLA-DQB1*040302 (OR: 0.40, 0.243-0.658) were present less frequently in the cervical cancer group (P < 0.05). The frequency of the HLA-DQB1 genotype in Uyghur was different from that reported previously in other areas. HLA-DQB1*0325 and HLA-DQB1*0332 probably act as cervical cancer susceptibility genes in Uyghur women from Xinjiang. In contrast, HLA-DQB1*0317 and HLA-DQB1*040302 may be protective genes. PMID- 26681220 TI - Association of single nucleotide polymorphisms in the CYP1B1 gene with the risk of primary open-angle glaucoma: a meta-analysis. AB - Mutations in the CYP1B1 gene were detected in primary open-angle glaucoma (POAG) patients. However, the association between these mutations and the incidence of POAG remains to be elucidated. Here, we have conducted a meta-analysis to analyze this correlation, using relevant studies obtained from an extensive search of various electronic databases, including EMBase, Web of Science, and PubMed. The extracted studies were selected for the meta-analysis based on the inclusion and exclusion criteria. The quality of each included study was assessed by the Newcastle-Ottawa scale (NOS), and the I2 value was calculated to evaluate the heterogeneity between studies. The combined effect size was presented as the odds ratio (OR), and confidence intervals (CI) were used to assess the association between POAG and CYP1B1 mutations. Eight studies, each with a high NOS score, were included in the analysis. Compared to the mutant allele, the wild-type allele of the rs180040 polymorphism in POAG patients showed a 12% decrease in OR (OR = 0.88, 95%CI = 0.76- 1.00); also, the wild-type allele of rs1056827 showed a 23% decrease in OR of the incidence of POAG (OR = 0.77, 95%CI = 0.60-0.99). However, the latter result was controversial. Polymorphisms at rs1056836, rs10012, and rs1056837 were not correlated with the incidence of POAG (using any evaluation model). In conclusion, three of the tested SNPs in the CYP1B1 gene were correlated with POAG; however, the SNPs rs180040 and rs1056827 showed an association with risk of POAG. These results must be further validated with larger-scale evaluations. PMID- 26681221 TI - Linkage analysis of SNPs in IGFBP-6 and its relation with the body sizes of pig. AB - Insulin-like growth factor binding protein-6 (IGFBP-6) is a member of the IGFBP family, which is known to be a key factor in regulating the effect of insulin like growth factor-2 (IGF-2) on the animal growth and development. Gene sequences of 3'-untranslated regions (UTR) and exon 4 of IGFBP-6 may influence the expression and proteolysis of IGFBP-6. In this study, 551 bp of the IGFBP-6 (including 257 bp of intron 3, exon 4, and 170 bp of 3' UTR) were sequenced and compared in the Bama and Tibetan mini-pigs, the Landrace and Large White pigs, and the Northeast wild boars. Six single nucleotide polymorphisms (SNPs) were detected in the IGFBP-6, in which T593C, T636C, and T745C were in intron 3, A67G was in exon 4, and G37A was in 3' UTR. T636C, T745C, and A67G were in linkage and formed four kinds of haplotypes, with CCT being the dominant haplotype in the mini-pigs; however, the haplotype block was not formed in the Landrace pigs and Large White pigs or the Northeast wild boars. Based on the above results, we concluded that the SNPs and haplotype of the IGFBP-6 may be related to the mini size formation of the pig. PMID- 26681222 TI - Expression and effect of serum interleukin-24 level on bone marrow mononuclear cells in children with acute leukemia. AB - To investigate the expression of interleukin-24 (IL-24) in the children with acute leukemia (AL) and its effect on the apoptosis of bone marrow mononuclear cells (BMMNCs) in vitro. Four groups were assessed: acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), non-leukemia, and healthy groups, 20 children in each group. ELISA was used to measure IL-24 serum level. The bone marrow was taken from patients and controls. BMMNCs were isolated and the DNA was analyzed by glucose electrophoresis. Flow cytometry was used to determine BMMNC apoptosis. The serum level of IL-24 in the ALL and AML groups were significantly higher than in the other two groups. There was no statistical difference between ALL and AML groups, either between non-leukemia and healthy groups. BMMNCs were exposed to IL-24 for 48 h, and the apoptotic rate of the group treated with 50 ng/ml IL-24 was obviously higher than that of control group (0 ng/mL). The serum IL-24 level of AL children decreased comparing to non-leukemia and healthy children, indicating that IL-24 can induce BMMNCs apoptosis of AL children in vitro. PMID- 26681223 TI - Expression of GRIN2A in benign and malignant nasopharyngeal diseases and its clinical significance. AB - The gene glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) is associated with development and neuron viability, and our previous studies showed it to be substantially methylated in nasopharyngeal carcinoma, indicating a link to this disease. The aim of this work was to investigate GRIN2A expression and its clinical significance in nasopharyngeal carcinoma, in contrast to nasopharyngitis and nasopharyngeal precancerous lesions. Fifty patients with nasopharyngeal carcinoma were selected as study subjects, while 28 chronic nasopharyngitis patients and 22 individuals with nasopharyngeal precancerous lesions were used as controls. Immunohistochemical analysis was used to study GRIN2A protein expression, and its relationship with nasopharyngeal carcinoma clinical stage and histopathological features were assessed. GRIN2A appeared as yellow staining in the cytoplasm or nucleus. It was strongly expressed in the nasopharyngeal epithelial tissues of patients with chronic nasopharyngitis and in nasopharyngeal precancerous lesions, the proportions of GRIN2A-positive cells being 82.1 and 72.7%, respectively. However, it was weakly expressed in nasopharyngeal carcinoma tissues, with 28.0% of cells testing positive (P < 0.001). No significant difference in the expression of GRIN2A was observed between different clinical stages and pathological grades. We conclude that weak GRIN2A expression is a major feature of nasopharyngeal carcinoma. PMID- 26681224 TI - Meta-analysis of the TNF-alpha-308G/A polymorphism and vitiligo risk. AB - Several case-control studies have been conducted to investigate the association between the tumor necrosis factor-alpha (TNF-alpha)-308G/A polymorphism and vitiligo risk. However, the results of these studies are inconsistent; therefore, we attempted to comprehensively evaluate the association between TNF-alpha-308G/A polymorphism and vitiligo risk via a meta-analysis. Studies reporting the association between TNF-alpha-308G/A polymorphism and vitiligo risk were retrieved from PubMed and EmBase databases. Data were extracted from these studies and the pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Six case-control studies including 1391 vitiligo cases and 2455 control subjects were included in this meta-analysis. The overall results showed the lack of a significant difference in TNF-alpha-308G/A genotype distribution between the patients and controls when the G allele and GG, GG + GA, GG, and GG genotypes were compared against the A allele and the GA + AA, AA, AA, and GA genotypes, respectively (ORs = 0.65, 0.53, 0.63, 0.41, 0.55; 95%CI = 0.35-1.23, 0.24-1.18, 0.10-4.09, 0.08-1.97, 0.25-1.21; P = 0.188, 0.121, 0.627, 0.264, 0.135, respectively). This meta-analysis suggests that the TNF-alpha 308G/A polymorphism may not be associated with vitiligo risk. As few studies are available in this field and current evidence remains limited, these results must be corroborated with well-designed and larger studies in the future. PMID- 26681225 TI - Prognostic value of miR-141 downregulation in gastric cancer. AB - Previous research has shown that microRNA-141 (miR-141) expression levels are associated with survival in several types of cancer. In the present study, we investigated the clinical significance and prognostic value of miR-141 in gastric cancer. Paired tissue specimens (tumor and adjacent normal mucosa) from 95 patients with gastric cancer were obtained at the Department of General Surgery, Xiangya Hospital, Central South University from March 2009 to February 2014. The levels of miR-141 in cancerous and corresponding non-cancerous tissues were detected by quantitative reverse transcription-polymerase chain reaction. Associations between clinicopathological parameters and miR-141 expression were evaluated using chi-square tests. Overall survival was calculated and survival curves were plotted using the Kaplan-Meier method; differences between groups were compared using log-rank tests. Compared to the matched normal gastric mucosa, gastric cancer tissues had significantly lower miR-141 expression levels (P < 0.001). This decreased miR-141 expression was significantly associated with tumor differentiation (P = 0.044), positive lymph node metastasis (P = 0.010), distant metastasis (P < 0.001), and advanced tumor-node-metastasis (TNM) stage (P < 0.001). Furthermore, a significant relationship was found between miR-141 expression and overall survival (P = 0.012, log-rank test). Cox regression analysis revealed that lymph node metastasis (P = 0.003), distant metastasis (P = 0.001), TNM stage (P < 0.001), and miR- 141 expression (P = 0.007) were independent prognostic factors in patients with gastric cancer. Our data provide evidence that the downregulation of miR-141 may contribute to the aggressive progression and poor prognosis of human gastric cancer. PMID- 26681226 TI - Identification of genes and pathways related to lipopolysaccharide signaling in duckling spleens. AB - Lipopolysaccharide (LPS), the major component of the outer cell wall of Gram negative bacteria, activates the immune system and threatens the health of livestock and poultry. However, little is known about the genes and pathways involved in the immune response of ducklings to LPS. To elucidate the genes involved in the response of 7-day-old duckling spleens treated with LPS, RNA from LPS-treated and control duckling spleens was analyzed by RNA-Seq. The results showed 11,095 and 10,840 genes with >10 clean reads in the LPS-treated and control groups, respectively. Among these genes, 89 were differentially expressed (log2 ratio >= 1, P <= 0.01, false discovery rate <= 0.001); 67 of these were upregulated and 22 were downregulated in the LPS-treated group compared to the control. GO and GO-rich analysis showed that differentially expressed genes were enriched in 13 functional categories (P < 0.05). Pathway analysis and pathway richness analysis showed that differentially expressed genes were enriched in six pathway categories (P < 0.05). Further analysis showed that some immune system related signaling pathways, such as the hematopoietic cell lineage, Toll-like receptor signaling pathway, T cell receptor signaling pathway, T cell receptor signaling pathway, complement and coagulation cascades, antigen processing and presentation, and chemokine signaling pathway, are active during the immune response. To confirm the RNA-Seq results, we detected CCL4, LBP, CD71, and STEAP3 expression using real-time PCR analysis, and the results were consistent with the RNA-Seq results. Our results provide new information on the genes involved in the immune response of duckling spleens to LPS. PMID- 26681228 TI - Wildlife and wildlife management in Tanzania. AB - Tanzania, arguably mainland Africa's most important nation for conservation, is losing habitat and natural resources rapidly. Moving away from a charcoal energy base and developing sustainable finance mechanisms for natural forests are critical to slowing persistent deforestation. Addressing governance and capacity deficits, including law enforcement, technical skills, and funding, across parts of the wildlife sector are key to effective wildlife protection. These changes could occur in tandem with bringing new models of natural resource management into play that include capacity building, corporate payment for ecosystem services, empowering nongovernmental organizations in law enforcement, greater private-sector involvement, and novel community conservation strategies. The future of Tanzania's wildlife looks uncertain-as epitomized by the current elephant crisis-unless the country confronts issues of governance, embraces innovation, and fosters greater collaboration with the international community. PMID- 26681227 TI - Expression of IL-21 in rats with inflammatory bowel disease. AB - The purpose of this study was to investigate the expression of interleukin (IL) 21 in rats with inflammatory bowel disease (IBD). Fifty adult Wistar rats were randomly divided into two groups: DSS, in which IBD was induced by giving the rats 7% DSS for seven days in their water, and a water control. Blood samples were collected and the concentration of IL-21 in serum was detected by enzyme linked immunosorbent assay. Colon tissue of rats was examined by immunohistochemical staining. Rats in the DSS group were lethargic, with matte coat color and decreasing body weight. In the DSS group, brown loss stool appeared after four days, and blood appeared in the stool along with dark red hematocele in the intestinal cavity after ten days. Rats in the control group were active and body weight increased regularly. Their stool was black and granular and the color of the intestinal canal was pink. The original body weight of all rats in both groups was similar but seven days after induction of IBD, the weight of the DSS rats dropped significantly compared to the control group (P < 0.05). Serum IL-21 levels were 1.37 +/- 0.43 pg/mL in the control group and 3.86 +/- 1.27 pg/mL in the DSS group (P < 0.05). More IL-21 positive cells were detected in the intestinal mucosal epithelial cell layer and the lamina propria of the submucosa in the DSS group than in the control group. In conclusion, IL-21 is involved in the pathological process of IBD. PMID- 26681229 TI - Evaluation of a wireless audio streaming accessory to improve mobile telephone performance of cochlear implant users. AB - OBJECTIVE: The objective of this study was to evaluate the potential improvement in word recognition in quiet and in noise obtained with use of a Bluetooth compatible wireless hearing assistance technology (HAT) relative to the acoustic mobile telephone condition (e.g. the mobile telephone receiver held to the microphone of the sound processor). DESIGN: A two-way repeated measures design was used to evaluate differences in telephone word recognition obtained in quiet and in competing noise in the acoustic mobile telephone condition compared to performance obtained with use of the CI sound processor and a telephone HAT. STUDY SAMPLE: Sixteen adult users of Nucleus cochlear implants and the Nucleus 6 sound processor were included in this study. RESULTS: Word recognition over the mobile telephone in quiet and in noise was significantly better with use of the wireless HAT compared to performance in the acoustic mobile telephone condition. Word recognition over the mobile telephone was better in quiet when compared to performance in noise. CONCLUSIONS: The results of this study indicate that use of a wireless HAT improves word recognition over the mobile telephone in quiet and in noise relative to performance in the acoustic mobile telephone condition for a group of adult cochlear implant recipients. PMID- 26681230 TI - Associations Between Spondyloarthritis Features and Magnetic Resonance Imaging Findings: A Cross-Sectional Analysis of 1,020 Patients With Persistent Low Back Pain. AB - OBJECTIVE: The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features. METHODS: We included patients ages 18 40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints. RESULTS: Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year). CONCLUSION: In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI. PMID- 26681231 TI - Clinical and immunological characteristics of a pediatric population with food protein-induced enterocolitis syndrome (FPIES) to fish. AB - BACKGROUND: Food protein-induced enterocolitis (FPIES) is an uncommon, non-IgE mediated food allergy that usually debuts in infancy with profuse vomiting, lethargy, and pallor 2-4 h following ingestion of the offending food. Its immune mechanism is not known. We aimed to describe the clinical features and outcome of children with fish-FPIES as well as to investigate on cellular immune response implicated. METHODS: Prospective and follow-up clinical study of children with FPIES by fish over a period between 2004 and 2013 was conducted. Measurement in vitro of both cytokine production in peripheral blood mononuclear cells (PBMCs) and expression of HLA-DR in monocyte-derived dendritic cells stimulated with fish extracts. RESULTS: Sixteen children (seven male and nine female) were included, with a mean age of onset at 10 months. Diagnosis was established after a median of 4 reactions. Twelve patients were treated in emergency room, and two were admitted in intensive care. Patch tests were positive in six patients. Skin prick tests (SPTs) and specific IgE to all fish tested were negative. Only three children reached tolerance at a mean age of 4.5 years. Eight children avoided fish because of positive oral food challenge (OFC) after 6 years of age. Other patients have not been challenged because of parent refusal to OFC or a recent diagnosis. TNF-alpha was increased in patients, and a significant elevation of the HLA-DR marker was also observed in these patients vs. control donors. CONCLUSIONS: FPIES caused by fish in many cases presents with severe clinical manifestations. Patch test has poor diagnostic value, and OFC is the gold standard to test tolerance. The cytokine TNF-alpha may be implicated in the clinical symptoms. Higher expression of HLA-DR in dendritic cells has also been detected in our patients. PMID- 26681232 TI - Improving quality of diabetes care by integrating psychological and social care for poorly controlled diabetes: 3 Dimensions of Care for Diabetes. AB - OBJECTIVE: Many people with persistent suboptimal diabetes control also have psychiatric morbidity and social problems which interfere with their ability to self-manage their diabetes. Current models of care in the UK do not integrate these different dimensions of care or address inequalities between physical and mental health. 3DFD (3 Dimensions of Care For Diabetes) integrated medical, psychological, and social care in diabetes for patients with persistent suboptimal glycemic control (HbA1c > 75 mmol/mol) despite guideline-based routine diabetes care, to improve glycemic control, reduce psychological distress, and improve social functioning. METHODS: The service delivered interventions including brief psychological therapies, mental health assessments, psychotropic medications, and social support, enhanced by patient-led case conferences aiming to optimize diabetes care. 3DFD measured changes in HbA1c, psychological functioning, quality of life, rates of unscheduled care, and levels of engagement with routine diabetes care at baseline and at 12 months. CONCLUSION: At 12-month follow-up, 3DFD patients achieved significant reductions in HbA1c of 15 mmol/mol, International Federation of Clinical Chemistry (1.4% Diabetes Control and Complications Trial) and improvements in depression scores and patient satisfaction. This model of care demonstrates that integrated care can improve diabetes outcomes in people with psychological and social comorbidities. PMID- 26681233 TI - Illness invalidation from spouse and family is associated with depression in diabetic patients with first superficial diabetic foot ulcers. AB - OBJECTIVES: (1) To assess the prevalence of depressive disorders in a sample of diabetic patients with their first superficial diabetic foot ulcer. (2) To evaluate the association between illness invalidation from spouse, family, and depressive disorders in those patients. METHODS: Depressive disorders and severity were diagnosed by the Structured Clinical Interview for DSM-IV Axis Iota disorders, clinical version, and the spouse and family scales of the Illness Invalidation Inventory, respectively (3*I). Physical functioning was also assessed using the Physical Component of The Short Form 36 item health-related quality of life questionnaire. RESULTS: The prevalence of depressive disorders was 27.50% (22/80). There was a significant decrease in physical health component summary mean score and a significant increase in ulcer size, Center for Epidemiologic Studies-Depression Scale, spouse discounting, spouse lack of understanding, and family discounting mean scores in the depressed group compared to the non-depressed group. Higher levels of spouse discounting, spouse understanding, and family discounting were significant predictors of diagnosis of depressive disorders and were strongly associated with increased severity of depressive symptoms in diabetic patients with first superficial diabetic foot ulcers. Poor physical functioning was associated with increased depressive symptom severity. CONCLUSION: This study demonstrated that illness invalidation from spouse and family is associated with diagnosis of depressive disorders and increased severity of depressive symptoms in diabetic patients with first superficial diabetic foot ulcers. PMID- 26681234 TI - Is serum 25-hydroxyvitamin D associated with depressive symptoms and suicidal ideation in Korean adults? AB - OBJECTIVE: Mixed results exist regarding the role of vitamin D deficiency in depression and suicidal ideation. The present study investigated the relationships among vitamin D, depressive symptoms, and suicidal ideation in a large representative of the general population of Korea. METHOD: The data from the fifth Korea National Health and Nutrition Examination Surveys conducted by the Division of Chronic Disease Surveillance, Korea Centers for Disease Control and Prevention, from 2010 to 2012 were investigated. A total of 15,695 subjects aged 20 and older were included in analysis. Depressive symptoms and suicidal ideation were evaluated based on self-report information. The serum 25 hydroxyvitamin D concentrations were measured by radioimmunoassay. The associations among vitamin D, depressive symptoms, and suicidal ideation were explored using multivariate logistic regression analysis adjusting for various confounding variables including sociodemographic and health-related variables. RESULTS: Serum 25-hydroxyvitamin D concentrations were not significantly different depending on the depressive symptoms (participant with depressive symptom, n = 2085, 17.10 ng/ml; without depressive symptom, n = 13,610, 17.36 ng/ml; p = 0.142) and suicidal ideation (participant with suicidal ideation, n = 2319, 17.31 ng/ml; without suicidal ideation, n = 13,374, 17.33 ng/ml; p = 0.926). After adjustment for sociodemographic and health-related factors, this lack of relationship was held consistent in the multivariate logistic regression. CONCLUSIONS: Significant associations were not observed among vitamin D, depressive symptoms, and suicidal ideation in Korean adults. Further studies are warranted to gain a better understanding of the association among vitamin D, depressive symptoms, and suicidal ideation. PMID- 26681235 TI - Relationship between the Self-Rating Anxiety Scale score and the success rate of 64-slice computed tomography coronary angiography. AB - OBJECTIVE: Computed tomography coronary angiography, a key method for obtaining coronary artery images, is widely used to screen for coronary artery diseases due to its noninvasive nature. In China, 64-slice computed tomography systems are now the most common models. As factors that directly affect computed tomography performance, heart rate and rhythm control are regulated by the autonomic nervous system and are highly related to the emotional state of the patient. The aim of this prospective study is to use a pre-computed tomography scan Self-Rating Anxiety Scale assessment to analyze the effects of tension and anxiety on computed tomography coronary angiography success. METHODS: Subjects aged 18-85 years who were planned to undergo computed tomography coronary angiography were enrolled; 1 to 2 h before the computed tomography scan, basic patient data (gender, age, heart rate at rest, and family history) and Self-Rating Anxiety Scale score were obtained. The same group of imaging department doctors, technicians, and nurses performed computed tomography coronary angiography for all the enrolled subjects and observed whether those subjects could finish the computed tomography coronary angiography scan and provide clear, diagnostically valuable images. Participants were divided into successful (obtained diagnostically useful coronary images) and unsuccessful groups. Basic data and Self-Rating Anxiety Scale scores were compared between the groups. RESULTS: The Self-Rating Anxiety Scale standard score of the successful group was lower than that of the unsuccessful group (P = 0.001). As the Self-Rating Anxiety Scale standard score rose, the success rate of computed tomography coronary angiography decreased. CONCLUSIONS: The Self-Rating Anxiety Scale score has a negative relationship with computed tomography coronary angiography success. ADVANCES IN KNOWLEDGE: Anxiety can be a disadvantage in computed tomography coronary angiography examination. The pre-computed tomography coronary angiography scan Self-Rating Anxiety Scale score may be a useful tool for assessing whether a computed tomography coronary angiography scan will be successful or not. PMID- 26681236 TI - Topiramate, zonisamide and weight loss in children and adolescents prescribed psychiatric medications: A medical record review. AB - BACKGROUND: Childhood obesity is a growing epidemic that is contributed to by the use of psychopharmacological agents, such as antipsychotics. This study represents a preliminary investigation into the effectiveness of two anticonvulsants that were hypothesized to reduce weight in a pediatric sample seeking treatment at a psychiatric clinic. METHODS: The electronic medical records of a university-based child and adolescent psychiatric clinic were reviewed for patients who were first prescribed either topiramate or zonisamide between 1 July 2011 and 30 June 2013. Based on inclusionary criteria, the review identified 47 children or adolescents. RESULTS: Multilevel modeling was utilized for study analyses. Including the full sample and controlling for confounders, anticonvulsant dosage was uniquely associated with an average reduction in body mass index of 1.3 (dosages above 200 mg) to 4.1 (dosages below 50 mg) every six months of treatment. Exlucing patients whose baseline body mass index was below 25.0 and controlling for confounders, anticonvulsant dosage was uniquely associated with an average reduction in body mass index of 3.2 (dosages above 200 mg) to 6.1 (dosages below 50 mg) every six months of treatment. Weight reduction was not statistically different between topiramate or zonisamide. Anticonvulsants were associated with an increase in body mass index, yet the benefits of the two anticonvulsants on weight loss remained despite the counteractive effects of antipsychotics. CONCLUSIONS: Results provide preliminary evidence that topiramate and zonisamide may be utilized for weight loss in a pediatric psychopharmacological treatment seeking sample, even if antipsychotics are also prescribed. A randomized controlled trial investigating the impact of topiramate and zonisamide on weight reduction is warranted. PMID- 26681237 TI - Predictors of psychotropic medication adherence among HIV+ individuals living with bipolar disorder. AB - OBJECTIVE: HIV infection and bipolar disorder are highly comorbid and associated with frontostriatal disruption, emotional dysregulation, and neurocognitive impairment. Psychiatric and cognitive factors have been linked to antiretroviral nonadherence; however, predictors of psychotropic adherence among HIV+ individuals with psychiatric comorbidities have not been explored. We evaluated predictors of psychotropic adherence among individuals with HIV infection and bipolar disorder. METHOD: Psychiatric medication adherence of 50 participants with HIV infection and bipolar disorder was tracked for 30 days using Medication Event Monitoring Systems. Participants completed neurocognitive, neuromedical, and psychiatric batteries. RESULTS: Mean psychotropic adherence rate was 78%; 56% of participants achieved >=90% adherence. Younger age and onset of depressive symptoms, more severe current depressive symptoms, number of previous psychiatric hospitalizations and suicide attempts, poorer neurocognition, and more negative attitudes and self-beliefs toward medications univariably predicted worse psychotropic adherence (p's < .10). A multivariable model demonstrated a combination of current depressive symptoms and more negative attitudes toward medications significantly predicting poorer adherence (R(2 )= 0.27, p < 0.003). Secondary analyses revealed an interaction between neurocognition and mood, such that individuals with HIV infection and bipolar disorder who had greater executive dysfunction and depressive symptoms evidenced the poorest psychotropic adherence (p < 0.001). CONCLUSIONS: Both psychiatric and neurocognitive factors contribute to poorer psychotropic adherence among HIV+ individuals with serious mental illness. Adherence interventions aimed at remediating these factors may be especially fruitful. PMID- 26681238 TI - Conceptualizing a subtype of patients with chronic pain: The necessity of obtaining a history of sexual abuse. AB - Lifetime history of sexual abuse is estimated to range between 15% and 25% in the general female population. Cross-sectional studies have shown that sexual assault survivors frequently report chronic musculoskeletal pain and functional somatic syndromes. Treating chronic pain with opioids went from being largely discouraged to being included in standards of care and titrating doses until patients self report adequate control has become common practice, with 8% to 30% of patients with chronic noncancer pain receiving opioids. In this clinical review, we will discuss the association between survivors of sexual assault and chronic pain/functional somatic syndromes. We will further review evidence-based treatment strategies for this "pain-prone phenotype." PMID- 26681239 TI - Clozapine-induced myocarditis may be associated with rapid titration: A case report verified with autopsy. AB - Clozapine-induced myocarditis is a poorly understood, rare, potentially fatal adverse drug reaction with absolute risks ranging from 7 to 34 per 1000 in Australia and 0.07-0.6 per 1000 in other countries. Hypersensitivity reactions have been postulated including some cases probably associated with rapid titrations. This case describes a 50-year-old African-American man with schizoaffective disorder, naive to clozapine, who probably died from clozapine induced myocarditis. He was started on 25 mg/day of clozapine and received 1625 mg over 14 days, prior to his death on day 15. The autopsy found predominantly lymphocytic infiltrate of the perivascular soft tissue and myocardium of the ventricles, with occasional eosinophils. Using the Liverpool ADR Causality Assessment Tool, it was deemed probable that the patient's death was secondary to myocarditis. The patient had fulminant death with no obvious changes in vital signs. Neither C-reactive protein nor troponin was measured, but it is unlikely that the results would have arrived in time to prevent the patient's death. Age, rapid titration, and concomitant use of valproate contributed to this case, which was probably an idiosyncratic adverse drug reaction associated with rapid titration. Lamotrigine-induced Stevens-Johnson syndrome also appears to be an idiosyncratic adverse drug reaction associated with rapid titration, but its incidence has been remarkably reduced since the recommended starting lamotrigine dose was reduced and corrected by the effect of inhibitors such as valproate. Similarly, clozapine-induced myocarditis incidence probably can be reduced with the use of slow titrations, including even slower titrations for patients with lower ability to metabolize clozapine, such as those taking valproate. PMID- 26681240 TI - Erratum. AB - Perez-San-Gregorio M. A., Fernandez-Jimenez E., Luque-Budia A., Martin-Rodriguez A. (2015). Anxiety and concerns in Spanish living kidney donor candidates. The International Journal of Psychiatry in Medicine, 50, 163-177. PMID- 26681241 TI - Monitoring HIV-1 Group M Subtypes in Yaounde, Cameroon Reveals Broad Genetic Diversity and a Novel CRF02_AG/F2 Infection. AB - Broad HIV-1 genetic diversity in Cameroon provides a unique opportunity to monitor HIV-1 evolution and allows the detection of novel strains. We have genetically characterized the HIV-1 subtypes found in 156 samples from 90 drug naive subjects in Yaounde, Cameroon collected from 2011 to 2013, using phylogenetic analysis of regions in gag and pol. We identified subtypes CRF02_AG (64.9%), CRF22_01A1 (7.1%), D (4.5%), F2 (3.9%), G (3.2%), CRF18_cpx (3.2%), CRF37_cpx (3.2%), CRF11_cpx (2.6%), CRF13_cpx (1.9%), A1 (1.3%), CRF01_AE (1.3%), CRF09_cpx (1.3%), A2 (0.6%), and H (0.6%). Sequence data for both the gag and pol regions were obtained from 62 subjects; for 59 of these subjects the two regions were identified as the same viral subtype while three subjects were discordant, A1/CRF02_AG (subject MDC006), CRF02_AG/F2 (subject MDC179), and a dual infection with CRF02_AG/F2 (subject MDC131). Longitudinal sequence data were obtained for 28 of these 62 subjects and confirmed the cross-sectional results. These data update subtype information for this area and highlight the necessity of such studies due to the numerous circulating subtypes, the ongoing superinfection, and the risk of emerging novel recombinant viruses. PMID- 26681255 TI - Polycatechol Nanoparticle MRI Contrast Agents. AB - Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID- 26681256 TI - "Cation-Stitching Cascade": exquisite control of terpene cyclization in cyclooctatin biosynthesis. AB - Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding the origin and mechanism of the selectivity of terpene cyclization is challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin biosynthesis by means of theoretical calculations combined with experimental methods. We show that the main framework of cyclooctatin is formed through domino-type carbocation transportation along the terpene chain, which we call a "cation-stitching cascade", including multiple hydrogen-shifts and a ring rearrangement that elegantly determine the stereoselectivity. PMID- 26681257 TI - Glutathione-dependent induction of local and systemic defense against oxidative stress by exogenous melatonin in cucumber (Cucumis sativus L.). AB - Melatonin is involved in defending against oxidative stress caused by various environmental stresses in plants. In this study, the roles of exogenous melatonin in regulating local and systemic defense against photooxidative stress in cucumber (Cucumis sativus) and the involvement of redox signaling were examined. Foliar or rhizospheric treatment with melatonin enhanced tolerance to photooxidative stress in both melatonin-treated leaves and untreated systemic leaves. Increased melatonin levels are capable of increasing glutathione (reduced glutathione [GSH]) redox status. Application of H2 O2 and GSH also induced tolerance to photooxidative stress, while inhibition of H2 O2 accumulation and GSH synthesis compromised melatonin-induced local and systemic tolerance to photooxidative stress. H2 O2 treatment increased the GSH/oxidized glutathione (GSSG) ratio, while inhibition of H2 O2 accumulation prevented a melatonin induced increase in the GSH/GSSG ratio. Additionally, inhibition of GSH synthesis blocked H2 O2 -induced photooxidative stress tolerance, whereas scavenging or inhibition of H2 O2 production attenuated but did not abolish GSH-induced tolerance to photooxidative stress. These results strongly suggest that exogenous melatonin is capable of inducing both local and systemic defense against photooxidative stress and melatonin-enhanced GSH/GSSG ratio in a H2 O2 -dependent manner is critical in the induction of tolerance. PMID- 26681262 TI - A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population. AB - BACKGROUND: With a healthcare system burdened by symptomatic and mental-health related conditions, the placebo effect may represent a useful clinical tool. First, however, there is a need to broaden research attention and investigate placebo effects outside laboratories and beyond experimental pain. This study investigated the effectiveness of a take-home placebo treatment in the short-term alleviation of stress, anxiety and symptoms of depression in a non-patient population. METHOD: A sample of 77 participants was randomized to either the 'oxytocin' treatment group (n = 22), the 'serotonin' treatment group (n = 22) or the wait-list control group (n = 33). The two treatment groups were given an 'anti-stress treatment spray' (placebo) to self-administer for 3 days, and completed online measures of perceived stress (Perceived Stress Scale-10), anxiety (Cognitive Somatic Anxiety Questionnaire) and symptoms of depression (Centre for Epidemiological Studies - Depression) before and after the 3-day protocol. RESULTS: Both the 'serotonin' and 'oxytocin' treatment sprays were effective in reducing symptoms of depression; however, only those in the 'oxytocin' group reported less stress and anxiety as compared with controls. Overall, the 'oxytocin' was perceived as more effective. CONCLUSION: Placebo effects can be translated to a real-life setting in the short-term reduction of stress, anxiety and symptoms of depression in a non-patient population. In treating psychological distress, placebos may be useful addition to the treatment repertoire. The information given with treatment may also be an important consideration for practitioners. PMID- 26681263 TI - Exploring the validity of the Fantastic Lifestyle Checklist in an inner city population of people presenting with suicidal behaviours. AB - PURPOSE: Although patients demonstrate a range of problematic health-related lifestyle behaviours preceding suicidal behaviour, there is little research that routinely measure these behaviours. This paper seeks to establish the utility of health-related lifestyle measure (Fantastic Lifestyle Checklist) in people presenting to a major inner city Emergency Department with a range of suicidal behaviours. METHODS: From 2007-2014, data from the 366 patients who had completed the Fantastic Lifestyle Checklist, after referral by the Emergency Department to a service for people with deliberate self-harm or suicidal ideation, were included in the analysis study. A Maximum Likelihood factor analysis was performed to assess the factor structure of the Fantastic Lifestyle Checklist and the resultant factors were explored in relation to measures of health; namely the Depression, Anxiety and Stress Scale and the 12-item Short-Form Health Survey. RESULTS: A three-component factor structure emerged comprising Component 1 'positive life investments', Component 2 'poor emotional regulation' and Component 3 'poor health behaviours'. There was a significant negative correlation between 'positive life investments' and each of the Depression, Anxiety and Stress scales subscales and significant positive associations with 'poor emotional regulation' and Short Form Health Survey-12 mental health scores. Only the Short Form Health Survey-12 physical health subscale was weakly correlated with 'poor health behaviours', in females. CONCLUSION: Our findings support the construct and concurrent validity of the Fantastic Lifestyle Checklist measure. The three factors obtained for the Fantastic Lifestyle Checklist were coherent and seem useful for research and clinical practice. PMID- 26681260 TI - The myofibroblast, a key cell in normal and pathological tissue repair. AB - Myofibroblasts are characterized by their expression of alpha-smooth muscle actin, their enhanced contractility when compared to normal fibroblasts and their increased synthetic activity of extracellular matrix proteins. Myofibroblasts play an important role in normal tissue repair processes, particularly in the skin where they were first described. During normal tissue repair, they appear transiently and are then lost via apoptosis. However, the chronic presence and continued activity of myofibroblasts characterize many fibrotic pathologies, in the skin and internal organs including the liver, kidney and lung. More recently, it has become clear that myofibroblasts also play a role in many types of cancer as stromal or cancer-associated myofibroblast. The fact that myofibroblasts are now known to be key players in many pathologies makes understanding their functions, origin and the regulation of their differentiation important to enable them to be regulated in normal physiology and targeted in fibrosis, scarring and cancer. PMID- 26681264 TI - Lymphoma developing during clozapine therapy. PMID- 26681259 TI - Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research. AB - Neuroactive steroids are endogenous neuromodulators synthesised in the brain that rapidly alter neuronal excitability by binding to membrane receptors, in addition to the regulation of gene expression via intracellular steroid receptors. Neuroactive steroids induce potent anxiolytic, antidepressant, anticonvulsant, sedative, analgesic and amnesic effects, mainly through interaction with the GABAA receptor. They also exert neuroprotective, neurotrophic and antiapoptotic effects in several animal models of neurodegenerative diseases. Neuroactive steroids regulate many physiological functions, such as the stress response, puberty, the ovarian cycle, pregnancy and reward. Their levels are altered in several neuropsychiatric and neurological diseases and both preclinical and clinical studies emphasise a therapeutic potential of neuroactive steroids for these diseases, whereby symptomatology ameliorates upon restoration of neuroactive steroid concentrations. However, direct administration of neuroactive steroids has several challenges, including pharmacokinetics, low bioavailability, addiction potential, safety and tolerability, which limit its therapeutic use. Therefore, modulation of neurosteroidogenesis to restore the altered endogenous neuroactive steroid tone may represent a better therapeutic approach. This review summarises recent approaches that target the neuroactive steroid biosynthetic pathway at different levels aiming to promote neurosteroidogenesis. These include modulation of neurosteroidogenesis through ligands of the translocator protein 18 kDa and the pregnane xenobiotic receptor, as well as targeting of specific neurosteroidogenic enzymes such as 17beta-hydroxysteroid dehydrogenase type 10 or P450 side chain cleavage. Enhanced neurosteroidogenesis through these targets may be beneficial not only for neurodegenerative diseases, such as Alzheimer's disease and age-related dementia, but also for neuropsychiatric diseases, including alcohol use disorders. PMID- 26681261 TI - Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications? AB - Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches. PMID- 26681265 TI - Borderline personality disorder and polycystic ovary syndrome. PMID- 26681266 TI - Brain metabolism changes with 18F-fluorodeoxy- glucose-positron emission tomography in a patient with Cotard's syndrome. PMID- 26681267 TI - Visual Access in Interpreter-Mediated Learning Situations for Deaf and Hard-of Hearing High School Students Where an Artifact Is in Use. AB - This article highlights interpreter-mediated learning situations for deaf high school students where such mediated artifacts as technical machines, models, and computer graphics are used by the teacher to illustrate his or her teaching. In these situations, the teacher's situated gestures and utterances, and the artifacts will contribute independent pieces of information. However, the deaf student can only have his or her visual attention focused on one source at a time. The problem to be addressed is how the interpreter coordinates the mediation when it comes to deaf students' visual orientation. The presented discourse analysis is based on authentic video recordings from inclusive learning situations in Norway. The theoretical framework consists of concepts of role, footing, and face-work (Goffman, E. (1959). The presentation of self in everyday life. London, UK: Penguin Books). The findings point out dialogical impediments to visual access in interpreter-mediated learning situations, and the article discusses the roles and responsibilities of teachers and educational interpreters. PMID- 26681268 TI - Reading Function and Content Words in Subtitled Videos. AB - In this study, we examined how function and content words are read in intra- and interlingual subtitles. We monitored eye movements of a group of 39 deaf, 27 hard of hearing, and 56 hearing Polish participants while they viewed English and Polish videos with Polish subtitles. We found that function words and short content words received less visual attention than longer content words, which was reflected in shorter dwell time, lower number of fixations, shorter first fixation duration, and lower subject hit count. Deaf participants dwelled significantly longer on function words than other participants, which may be an indication of their difficulty in processing this type of words. The findings are discussed in the context of classical reading research and applied research on subtitling. PMID- 26681269 TI - Examination of the auxin hypothesis of phytomelatonin action in classical auxin assay systems in maize. AB - Melatonin has been found in a wide range of plant groups. Its physiological roles have been suggested to be diverse in stress protection and plant growth regulation. An attractive hypothesis is that phytomelatonin acts as an auxin to regulate plant development. However, the auxin hypothesis is controversial, since both supporting and contradictory evidence has been reported. We systematically investigated whether melatonin fulfilled the definition for auxin in maize (Zea mays). Melatonin did not affect coleoptile elongation, root growth or ACC synthase gene expression, contrary to 10(-5)M IAA in our assay system. The auxin hypothesis of phytomelatonin action is not supported in maize, because melatonin appeared inactive in all of the auxin activity tests. On the other hand, melatonin was active in the protection of maize growth against salt stress, suggesting its importance in another context. PMID- 26681270 TI - Learning with older people--Outcomes of a quasi-experimental study. AB - BACKGROUND: Nursing students' interest in older people nursing needs to be enhanced, as there is a demand for competent nurses who prefer to work in older people nursing. Educational approaches involving older people are encouraging; they increase positive learning outcomes. OBJECTIVES: The aim of this study was to evaluate the outcomes of the Learning with Older People Programme (LOPP) in terms of nursing students' interest in older people nursing, their attitudes towards older people and their knowledge level about ageing. DESIGN: A quasi experimental, pre-post-test design with non-equivalent comparison group was used. SETTINGS: Two different Finnish nursing schools geographically apart from each other. PARTICIPANTS: A nonprobability, convenience sample of nursing students (n=87; n=46 in the intervention group, n=41 in the comparison group) in the middle of their 3.5 year bachelor degree studies and enrolled in compulsory theoretical older people nursing courses participated in the study. METHODS: Data were collected in 2014 using a structured questionnaire that included background questions, students' interest in older people nursing as a primary outcome measure and their attitudes towards older people and knowledge level about ageing as secondary outcome measures. The data were analysed statistically. RESULTS: In the intervention group, students' interest in older people nursing was significantly higher and their attitudes towards older people were more positive than those of students in the comparison group. There were no significant differences between the groups in terms of the students' knowledge level about ageing. CONCLUSIONS: An educational approach involving older people resulted in encouraging outcomes. It is worth considering whether or not older people could be a valuable resource for nursing education. PMID- 26681271 TI - Erratum. PMID- 26681274 TI - Adolescent health: boys matter too. PMID- 26681272 TI - Use of TachoSil((r)) patches to prevent pancreatic leaks after distal pancreatectomy: a prospective, multicenter, randomized controlled study. AB - BACKGROUND: We performed a prospective, multicenter, randomized controlled study to investigate the clinical outcomes, including postoperative pancreatic fistulas (POPF), after using the TachoSil(r) patch in distal pancreatectomy (NCT01550406). METHODS: Between June 2012 and September 2014, 101 patients at five centers were randomized into Control (n = 53) and TachoSil (n = 48) groups. In all patients, the pancreas was resected using a stapler with Endo-GIATM staples. The TachoSil patch was wrapped around the pancreatic stump only in the TachoSil group, not in Control group. RESULTS: The patient characteristics, including age and diagnosis, were comparable in both groups. The mean operation time (159.4 vs. 172.3 min, P = 0.081) and postoperative hospital stay (10.0 vs. 9.7 days, P = 0.279) were similar in the Control and TachoSil groups, respectively. The overall incidence of POPF was 62.4% (n = 63). The distribution of grades A, B, and C POPF was similar in the Control (n = 14/14/1) and TachoSil (n = 23/11/0) groups, as were the overall incidence (54.7% vs. 70.8%, P = 0.095) and the incidence of grade B and C POPF (28.3% vs. 22.9%, P = 0.536). CONCLUSION: This study showed that the TachoSil(r) patch did not reduce the incidence of POPF after distal pancreatectomy. PMID- 26681273 TI - Tumor volume as a predictor of survival in human papillomavirus-positive oropharyngeal cancer. AB - BACKGROUND: Increasing evidence exists that tumor volume may be a superior prognostic model than traditional TNM staging. It has been observed that oropharyngeal squamous cell carcinoma (oropharyngeal SCC) in the setting of human papillomavirus (HPV) positivity have a greater propensity for cystic nodal metastases, and, thus, presumably larger volume with relatively smaller primary tumors. The influence of HPV status on the predictive value of tumor volume is unknown. METHODS: Fifty-three patients with HPV-positive oropharyngeal SCC were treated with definitive chemotherapy and intensity-modulated radiotherapy (IMRT). RESULTS: The estimated 2-year overall survival (OS) and disease-free survival (DFS) was 92.2% and 83.6%, respectively. Nodal classification did not predict OS (p = .096) or DFS (p = .170). Similarly, T classification did not predict OS (p = .057) or DFS (p = .309). Lower nodal volume was associated with greater DFS (p = .001). CONCLUSION: Nodal tumor volume was found to be predictive of DFS. DFS was best predicted by nodal gross tumor volume (GTV) at 24 months. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1613-E1617, 2016. PMID- 26681275 TI - The death of AIDS--expected or exaggerated? PMID- 26681276 TI - Nepal: man-made disaster looms. PMID- 26681277 TI - Opening the GATE to inclusion for people with disabilities. PMID- 26681280 TI - 5 years of austerity takes its toll on Greek health care. PMID- 26681281 TI - Ethiopia could be a model country for tuberculosis control. PMID- 26681282 TI - Health consequences of the blockade in Nepal. PMID- 26681283 TI - Tackling preventable diseases in Yemen. PMID- 26681284 TI - Snake bites and antivenom shortage in Africa. PMID- 26681285 TI - Treating snake bites--a call for partnership. PMID- 26681286 TI - ReEBOV Antigen Rapid Test kit for Ebola. PMID- 26681287 TI - ReEBOV Antigen Rapid Test kit for Ebola. PMID- 26681288 TI - ReEBOV Antigen Rapid Test kit for Ebola. PMID- 26681289 TI - ReEBOV Antigen Rapid Test kit for Ebola. PMID- 26681290 TI - ReEBOV Antigen Rapid Test kit for Ebola - Authors' reply. PMID- 26681291 TI - Glomerulonephritis triggered by a chronically infected left ventricular assist device. PMID- 26681292 TI - Glomerulonephritis from a chronically infected implanted device. PMID- 26681293 TI - Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004-2011: a cohort study. AB - BACKGROUND: Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity. METHODS: Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004-2011 were used to construct comorbidity histories. Sex specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity. RESULTS: After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used. CONCLUSIONS: The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM. PMID- 26681294 TI - Your Place or Mine? Does the Sleep Location Matter in Young Couples? AB - This study sought to characterize the impact of sleep location (own sleeping environment vs. partner's sleeping environment), social setting (sleeping in pairs vs. sleeping alone), and sex on sleep. An experimental 2 x 2 (sleep location x social setting) within-subject design was employed with 15 young heterosexual couples. The results suggest that sleep location does not appear to have a strong and consistent effect on sleep quantity or quality. The social setting had a specific effect in heterosexual young men, who were found to sleep longer and rise later when cosleeping with their partner. In contrast, we did not find any significant effect of the social setting on sleep continuity parameters in women. In both sexes, sleep quality was perceived to be better when sleeping in pairs. However, there was a higher concordance of the partners' body movements in cosleeping nights compared to the sleeping alone condition. PMID- 26681295 TI - Modelling the trends of inpatient and outpatient rehabilitation for methamphetamine in the Western Cape province of South Africa. AB - BACKGROUND: Dependence on methamphetamine remains one of the major health and social problem in the Western Cape province of South Africa. We consider a mathematical model that takes into account two forms of rehabilitation, namely; inpatient and outpatient. We examine the trends of these two types of rehabilitation. We also seek to investigate the global dynamics of the developed methamphetamine epidemic model. METHODS: The model is designed by likening the initiation process to an infection that spreads in a community through interactions between methamphetamine users and non-users. We make use of Lyapunov functions obtained from a suitable combination of common quadratic and Volterra type functions to establish the global stability of the methamphetamine persistent steady state. The least squares curve fit routine (lsqcurvefit) in Matlab with optimization is used to estimate the parameter values. RESULTS: The model analysis shows that the model has two equilibria, the methamphetamine free equilibrium and the methamphetamine persistent equilibrium, that are both globally stable when the threshold R(a) < 1 and R(a) > 1, respectively. Upon fitting the model to data on drug users under rehabilitation, parameter values that give the best fit were obtained. The projections carried out the long term trends of these forms of rehabilitation. CONCLUSION: The results suggest that inpatient rehabilitation programs have an increased potential of enhancing the chances of recovery for methamphetamine addicts. PMID- 26681296 TI - Acute Focal Bacterial Nephritis Can Lead to Unnecessary Invasive Procedures: A Report of Three Cases. AB - Acute focal bacterial nephritis (AFBN) is a rarely diagnosed interstitial bacterial infection of the kidney. Due to the non-specific clinical presentation of this entity, correct diagnosis can be challenging. In this work, we present three cases of AFBN aiming to stress the diversity of clinical presentation associated with the disease and the fact that patients with AFBN are at risk of undergoing unnecessary invasive procedures. The employment of invasive diagnostic and therapeutic procedures on the management of AFBN should be limited, as the majority of patients respond well to conservative therapy. PMID- 26681297 TI - Bereaved families and the coronial response to traumatic workplace fatalities: Organizational perspectives. AB - Work remains a significant source of illness, injury, and death in developed countries. In Australia, for example, over 2,000 people die from work-related causes each year, with heavy social, economic, and personal costs (Safe Work Australia, 2013a ). Most die as a result of work-related disease. However, many die from trauma. In 2012, 223 workers were fatally injured in Australia and in the United States the figure was 4,383 (Bureau of Labor Statistics, 2014 ; Safe Work Australia, 2013b ). Apart from the immediate tragedy of each worker's death, these deaths affect the victim's immediate family, wider family, friends, and co workers. It has been estimated that, on average, every death has an impact on at least 20 other people (Dyregrov, Nordanger, & Dyregrov, 2003 ), especially when the deceased had several families, which is an increasingly common phenomenon (OECD, 2014 ). Little is known, however, about how regulatory responses following a traumatic workplace fatality meet the needs of surviving families. With a focus on the coronial investigation, this article provides information about the regulatory responses to a traumatic workplace fatality and examines how various organizations involved in the coronial process following the death viewed its ability to accommodate the needs and wishes of surviving families. PMID- 26681298 TI - Targeting druggable enzymome by exploiting natural medicines: An in silico-in vitro integrated approach to combating multidrug resistance in bacterial infection. AB - CONTEXT: Antibiotic resistance is a major clinical and public health problem. Development of new therapeutic approaches to prevent bacterial multidrug resistance during antimicrobial chemotherapy has thus been becoming a primary consideration in the medicinal chemistry community. OBJECTIVE: We described a new strategy that combats multidrug resistance by using natural medicines to target the druggable enzymome (i.e., enzymatic proteome) of Staphylococcus aureus. MATERIALS AND METHODS: A pipeline of integrating in silico analysis and in vitro assay was purposed to identify antibacterial agents from a large library of natural products with diverse structures, high drug-likeness, and relatively low flexibility, with which a systematic interactome of 826 natural product candidates with 125 functionally essential S. aureus enzymes was constructed via a high-throughput cross-docking approach. The obtained docking score matrix was then converted into an array of synthetic scores; each corresponds to a natural product candidate. By systematically examining the docking results, a number of highly promising candidates with potent antibacterial activity were suggested. RESULTS: Three natural products, i.e., radicicol, jorumycin, and amygdalin, have been determined to possess strong broad-spectrum potency combating both the drug resistant and drug-sensitive strains (MIC value <10 MUg/ml). In addition, some natural products such as tetrandrine, bilobalide, and arbutin exhibited selective inhibition on different strains. DISCUSSION AND CONCLUSION: Combined quantum mechanics/molecular mechanics analysis revealed diverse non-bonded interactions across the complex interfaces of newly identified antibacterial agents with their putative targets GyrB ATPase and tyrosyl-tRNA synthetase. PMID- 26681300 TI - Care Seeking Patterns Among Women Who Have Experienced Gender-Based Violence in Afghanistan. AB - This study explored patterns of abuse and care seeking among women victims of gender-based violence (GBV) in Afghanistan. Individual, semi-structured interviews were conducted with 22 Afghan women (M age = 19 years) living in a shelter for victims of GBV. Interviews were analyzed thematically. Participants reported experiencing multiple forms of abuse. The majority received medical treatment for abuse-related health concerns. However, less than half reported abuse to health care providers or were asked by health care providers about the context of their injuries. Strategies to improve health care responses to GBV are needed to ensure safety and support for Afghan women. PMID- 26681299 TI - General Practitioners' Concerns About Online Patient Feedback: Findings From a Descriptive Exploratory Qualitative Study in England. AB - BACKGROUND: The growth in the volume of online patient feedback, including online patient ratings and comments, suggests that patients are embracing the opportunity to review online their experience of receiving health care. Very little is known about health care professionals' attitudes toward online patient feedback and whether health care professionals are comfortable with the public nature of the feedback. OBJECTIVE: The aim of the overall study was to explore and describe general practitioners' attitudes toward online patient feedback. This paper reports on the findings of one of the aims of the study, which was to explore and understand the concerns that general practitioners (GPs) in England have about online patient feedback. This could then be used to improve online patient feedback platforms and help to increase usage of online patient feedback by GPs and, by extension, their patients. METHODS: A descriptive qualitative approach using face-to-face semistructured interviews was used in this study. A topic guide was developed following a literature review and discussions with key stakeholders. GPs (N=20) were recruited from Cambridgeshire, London, and Northwest England through probability and snowball sampling. Interviews were transcribed verbatim and analyzed in NVivo using the framework method, a form of thematic analysis. RESULTS: Most participants in this study had concerns about online patient feedback. They questioned the validity of online patient feedback because of data and user biases and lack of representativeness, the usability of online patient feedback due to the feedback being anonymous, the transparency of online patient feedback because of the risk of false allegations and breaching confidentiality, and the resulting impact of all those factors on them, their professional practice, and their relationship with their patients. CONCLUSIONS: The majority of GPs interviewed had reservations and concerns about online patient feedback and questioned its validity and usefulness among other things. Based on the findings from the study, recommendations for online patient feedback website providers in England are given. These include suggestions to make some specific changes to the platform and the need to promote online patient feedback more among both GPs and health care users, which may help to reduce some of the concerns raised by GPs about online patient feedback in this study. PMID- 26681301 TI - Imaging Active Surface Processes in Barnacle Adhesive Interfaces. AB - Surface plasmon resonance imaging (SPRI) and voltammetry were used simultaneously to monitor Amphibalanus (=Balanus) amphitrite barnacles reattached and grown on gold-coated glass slides in artificial seawater. Upon reattachment, SPRI revealed rapid surface adsorption of material with a higher refractive index than seawater at the barnacle/gold interface. Over longer time periods, SPRI also revealed secretory activity around the perimeter of the barnacle along the seawater/gold interface extending many millimeters beyond the barnacle and varying in shape and region with time. Ex situ experiments using attenuated total reflectance infrared (ATR-IR) spectroscopy confirmed that reattachment of barnacles was accompanied by adsorption of protein to surfaces on similar time scales as those in the SPRI experiments. Barnacles were grown through multiple molting cycles. While the initial reattachment region remained largely unchanged, SPRI revealed the formation of sets of paired concentric rings having alternately darker/lighter appearance (corresponding to lower and higher refractive indices, respectively) at the barnacle/gold interface beneath the region of new growth. Ex situ experiments coupling the SPRI imaging with optical and FTIR microscopy revealed that the paired rings coincide with molt cycles, with the brighter rings associated with regions enriched in amide moieties. The brighter rings were located just beyond orifices of cement ducts, consistent with delivery of amide rich chemistry from the ducts. The darker rings were associated with newly expanded cuticle. In situ voltammetry using the SPRI gold substrate as the working electrode revealed presence of redox active compounds (oxidation potential approx 0.2 V vs Ag/AgCl) after barnacles were reattached on surfaces. Redox activity persisted during the reattachment period. The results reveal surface adsorption processes coupled to the complex secretory and chemical activity under barnacles as they construct their adhesive interfaces. PMID- 26681302 TI - Correction: Expression Analysis of CB2-GFP BAC Transgenic Mice. PMID- 26681303 TI - Erratum: A Novel, Stable, Estradiol-Stimulating, Osteogenic Yam Protein with Potential for the Treatment of Menopausal Syndrome. PMID- 26681304 TI - Mummy days: ten years later. PMID- 26681305 TI - Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease. AB - Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center. Clinical, laboratory, and echocardiographic data from 143 acute KD subjects were analyzed. PA dilation was documented in 23 subjects (16.1 %); these subjects had higher median right ventricle myocardial performance index (RV MPI), higher ratio of early tricuspid inflow velocity to tricuspid annular early diastolic velocity (TV E/e'), and lower median TV e' velocity compared to the non-PA dilation group (0.50 vs 0.38 p < 0.01, 4.2 vs 3.6 p < 0.05, and 13.5 vs 15.2 cm/s p < 0.01, respectively). Almost all subjects with PA dilation had improved PA Z-score, RV MPI, and TV E/e' in the subacute phase (p < 0.01). There were no significant differences in indices of left ventricle function between PA dilation group and non-PA dilation group. In summary, PA dilation was documented in 16 % of acute KD subjects. These subjects were more likely to have echocardiographic indices consistent with isolated RV dysfunction that improved in the subacute phase. The long-term consequence of these findings will require longitudinal studies of this patient population. PMID- 26681306 TI - Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa): a systematic review of the literature and meta-analysis. AB - PURPOSE: Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa) is a rare tumour. Prognosis and optimal management are not well established. In view of a case managed in our Centre, we performed a systematic review and meta-analysis. METHOD: Systematic review of medical electronic databases for published data (1950-12/10/2015). No RCTs identified. Individual patient data detracted from case reports and case series were analysed RESULTS: In total, 73 female and 5 male cases of PRMCa identified including our case. Median age at diagnosis was 42.0 years (range 18-86 years), with women being significantly younger than men at diagnosis (42.0 years versus 62.2 years, p = 0.005). A palpable abdominal mass and abdominal pain were the most common presentations in 42.9 and 23.8 % of cases, respectively. Twenty-six women were <38 years old. There were 16 women <38 years old that had surgical data reported, of which 14 underwent fertility sparing surgery with excision of the mass. Adjuvant chemotherapy was given in 24.1 % (13/72) women. Follow-up ranged from 1 to 130 months with a median of 15 months. Of the 57 cases that had follow-up reported, recurrence occurred in 23 cases (40.4 %) within a median of 8 months from diagnosis. Median disease-free survival was 15 months (range 1-130 months). Of the women who recurred, 14 died of their disease giving 1, 2 and 5-year disease-specific survival rates of 85.9, 80.7 and 75.4 %, respectively. CONCLUSION: PRMCa are rare and potentially aggressive tumours that often occur in young women. Removal of the tumour, adequate staging and adjuvant chemotherapy needs to be considered. PMID- 26681307 TI - Identification of quantitative trait loci for body temperature, body weight, breast yield, and digestibility in an advanced intercross line of chickens under heat stress. AB - BACKGROUND: Losses in poultry production due to heat stress have considerable negative economic consequences. Previous studies in poultry have elucidated a genetic influence on response to heat. Using a unique chicken genetic resource, we identified genomic regions associated with body temperature (BT), body weight (BW), breast yield, and digestibility measured during heat stress. Identifying genes associated with a favorable response during high ambient temperature can facilitate genetic selection of heat-resilient chickens. METHODS: Generations F18 and F19 of a broiler (heat-susceptible) * Fayoumi (heat-resistant) advanced intercross line (AIL) were used to fine-map quantitative trait loci (QTL). Six hundred and thirty-one birds were exposed to daily heat cycles from 22 to 28 days of age, and phenotypes were measured before heat treatment, on the 1st day and after 1 week of heat treatment. BT was measured at these three phases and BW at pre-heat treatment and after 1 week of heat treatment. Breast muscle yield was calculated as the percentage of BW at day 28. Ileal feed digestibility was assayed from digesta collected from the ileum at day 28. Four hundred and sixty eight AIL were genotyped using the 600 K Affymetrix chicken SNP (single nucleotide polymorphism) array. Trait heritabilities were estimated using an animal model. A genome-wide association study (GWAS) for these traits and changes in BT and BW was conducted using Bayesian analyses. Candidate genes were identified within 200-kb regions around SNPs with significant association signals. RESULTS: Heritabilities were low to moderate (0.03 to 0.35). We identified QTL for BT on Gallus gallus chromosome (GGA)14, 15, 26, and 27; BW on GGA1 to 8, 10, 14, and 21; dry matter digestibility on GGA19, 20 and 21; and QTL of very large effect for breast muscle yield on GGA1, 15, and 22 with a single 1 Mb window on GGA1 explaining more than 15% of the genetic variation. CONCLUSIONS: This is the first study to estimate heritabilities and perform GWAS using this AIL for traits measured during heat stress. Significant QTL as well as low to moderate heritabilities were found for each trait, and these QTL may facilitate selection for improved animal performance in hot climatic conditions. PMID- 26681308 TI - A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51. AB - Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act in a recessive mode of inheritance. Here we report on a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, 'FA-R', which appears to be the first subtype of FA caused by a dominant-negative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and paediatric cancers. Together with the recent reports on RAD51-associated congenital mirror movement disorders, our results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility. PMID- 26681310 TI - Recommendations from the EGAPP Working Group: does the use of Oncotype DX tumor gene expression profiling to guide treatment decisions improve outcomes in patients with breast cancer? AB - of RECOMMENDATIONS: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found insufficient evidence to recommend for or against the use of Oncotype DX testing to guide chemotherapy treatment decisions in women with hormone receptor-positive, lymph node-negative, or lymph node positive early breast cancer who are receiving endocrine therapy. This recommendation statement updates a 2009 EGAPP statement on the use of gene expression profiling tests in breast cancer. Evidence of clinical validity for Oncotype DX was confirmed as adequate. With regard to clinical utility, although there was evidence from prospective retrospective studies that the Oncotype DX test predicts benefit from chemotherapy, and there was adequate evidence that the use of Oncotype DX gene expression profiling in clinical practice changes treatment decisions regarding chemotherapy, no direct evidence was found that the use of Oncotype DX testing leads to improved clinical outcomes. RATIONALE: In women with early-stage invasive breast cancer, gene expression profiling is increasingly being used as an aid to estimate the likely benefit from chemotherapy treatment. In a previous recommendation statement, the EGAPP Working Group (EWG) found adequate evidence for clinical validity of some gene expression profiling tests in predicting distant disease recurrence in women with early stage, hormone receptor-positive, lymph-node-negative breast cancer who are treated with tamoxifen, but insufficient evidence that use of these tests for decisions about chemotherapy treatment has clinical utility. The current recommendation statement updates these findings for Oncotype DX and extends them to the population of women with lymph node-positive disease, using evidence from recent systematic reviews and other sources. ANALYTIC VALIDITY: The previous recommendation statement found that evidence was inadequate to enable quantitative determination of the analytic validity of Oncotype DX. Analytic validity was not reconsidered in the updated recommendation statement because there remains no gold-standard test for comparison. CLINICAL VALIDITY: The EWG found that new evidence published since the original evidence review supports the clinical validity of Oncotype DX in predicting risk of distant metastases in women with hormone receptor-positive, early-stage breast cancer that is either node-negative or node-positive. CLINICAL UTILITY: No direct evidence was found that use of Oncotype DX tumor gene expression profiling to guide treatment decisions improves clinical outcomes in women with early breast cancer. There is indirect evidence, from prospective retrospective studies on archived tissue samples from randomized controlled trials, that the Oncotype DX test can predict benefit from chemotherapy. Large, prospective, randomized, controlled trials currently in progress may provide evidence of clinical utility. CONTEXTUAL ISSUES: Until definitive evidence for clinical utility is available, clinicians must decide on a case-by-case basis whether to offer the test to patients. Although Oncotype DX testing has been reported, on the basis of economic modeling studies, to be cost-effective in several different health-care systems and to save costs in the US health-care setting, studies were based on assumptions regarding the clinical utility of the test that require confirmation by clinical trial results.Genet Med 18 8, 770-779. PMID- 26681311 TI - Newborn testing and screening by whole-genome sequencing. PMID- 26681309 TI - Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma. AB - PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c. 34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736. PMID- 26681312 TI - Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. AB - PURPOSE: Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance. METHODS: Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history. RESULTS: Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2. CONCLUSION: The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes.Genet Med 18 8, 823-832. PMID- 26681313 TI - Exploring the landscape of pathogenic genetic variation in the ExAC population database: insights of relevance to variant classification. AB - PURPOSE: We evaluated the Exome Aggregation Consortium (ExAC) database as a control cohort to classify variants across a diverse set of genes spanning dominant and recessively inherited disorders. METHODS: The frequency of pathogenic variants in ExAC was compared with the estimated maximal pathogenic allele frequency (MPAF), based on the disease prevalence, penetrance, inheritance, allelic and locus heterogeneity of each gene. Additionally, the observed carrier frequency and the ethnicity-specific variant distribution were compared between ExAC and the published literature. RESULTS: The carrier frequency and ethnic distribution of pathogenic variants in ExAC were concordant with reported estimates. Of 871 pathogenic/likely pathogenic variants across 19 genes, only 3 exceeded the estimated MPAF. Eighty-four percent of variants with ExAC frequencies above the estimated MPAF were classified as "benign." Additionally, 20% of the cardiac and 19% of the Lynch syndrome gene variants originally classified as "VUS" occurred with ExAC frequencies above the estimated MPAF, making these suitable for reassessment. CONCLUSIONS: The ExAC database is a useful source for variant classification and is not overrepresented for pathogenic variants in the genes evaluated. However, the mutational spectrum, pseudogenes, genetic heterogeneity, and paucity of literature should be considered in deriving meaningful classifications using ExAC.Genet Med 18 8, 850 854. PMID- 26681314 TI - Direct-to-consumer genetic testing: a revised position statement of the American College of Medical Genetics and Genomics. AB - DISCLAIMER: These recommendations are designed primarily as an educational resource for medical geneticists and other health-care providers to help them provide quality medical genetics services. Adherence to these recommendations does not necessarily assure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, geneticists and other clinicians should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from the recommendations. PMID- 26681315 TI - Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology targeted drugs: a mapping of ClinicalTrials.gov. AB - PURPOSE: The aim of this study was to describe pharmacogenomics-based inclusion criteria (enrichment) and the main characteristics of clinical trials involving oncology-targeted therapies. METHODS: Clinical trials of oncology-targeted therapies approved after 2005 with pharmacogenomic testing required or recommended in their label were retrieved from a mapping of the ClinicalTrials.gov database. RESULTS: We examined information for 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) were enriched on another biomarker, whereas 270 trials (31%) included all patients. The median proportion of trials corresponding to both the drug's indication and drug's target was 35%. Of the 361 trials that tested drugs in another disease than the first one in the label, 219 (61%) were without enrichment and 87 (24%) were actually enriched but on another biomarker than the first one in the label. CONCLUSION: Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most targeted therapies have been developed only using biomarker-positive patients; therefore, exclusion of biomarker-negative patients from treatment relies on only preclinical data and on biological understanding of the disease and target.Genet Med 18 8, 796-805. PMID- 26681316 TI - VisCap: inference and visualization of germ-line copy-number variants from targeted clinical sequencing data. AB - PURPOSE: To develop and validate VisCap, a software program targeted to clinical laboratories for inference and visualization of germ-line copy-number variants (CNVs) from targeted next-generation sequencing data. METHODS: VisCap calculates the fraction of overall sequence coverage assigned to genomic intervals and computes log2 ratios of these values to the median of reference samples profiled using the same test configuration. Candidate CNVs are called when log2 ratios exceed user-defined thresholds. RESULTS: We optimized VisCap using 14 cases with known CNVs, followed by prospective analysis of 1,104 cases referred for diagnostic DNA sequencing. To verify calls in the prospective cohort, we used droplet digital polymerase chain reaction (PCR) to confirm 10/27 candidate CNVs and 72/72 copy-neutral genomic regions scored by VisCap. We also used a genome wide bead array to confirm the absence of CNV calls across panels applied to 10 cases. To improve specificity, we instituted a visual scoring system that enabled experienced reviewers to differentiate true-positive from false-positive calls with minimal impact on laboratory workflow. CONCLUSIONS: VisCap is a sensitive method for inferring CNVs from targeted sequence data from targeted gene panels. Visual scoring of data underlying CNV calls is a critical step to reduce false positive calls for follow-up testing.Genet Med 18 7, 712-719.Genetics in Medicine (2016); 18 7, 712-719. doi:10.1038/gim.2015.156. PMID- 26681317 TI - Acetyl-Phosphate Is Not a Global Regulatory Bridge between Virulence and Central Metabolism in Borrelia burgdorferi. AB - In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2 (BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway. Previous investigations have attempted to identify the phosphate donor of Rrp2, including the cognate histidine kinase, Hk2 (BB0764), non-cognate histidine kinases such as Hk1, CheA1, and CheA2, and small molecular weight P donors such as carbamoyl-phosphate and acetyl-phosphate (AcP). In a report by Xu et al., exogenous sodium acetate led to increased expression of RpoS and OspC and it was hypothesized this effect was due to increased levels of AcP via the enzyme AckA (BB0622). Genome analyses identified only one pathway that could generate AcP in B. burgdorferi: the acetate/mevalonate pathway that synthesizes the lipid, undecaprenyl phosphate (C55-P, lipid I), which is essential for cell wall biogenesis. To assess the role of AcP in Rrp2-dependent regulation of RpoS and OspC, we used a unique selection strategy to generate mutants that lacked ackA (bb0622: acetate to AcP) or pta (bb0589: AcP to acetyl-CoA). These mutants have an absolute requirement for mevalonate and demonstrate that ackA and pta are required for cell viability. When the DeltaackA or Deltapta mutant was exposed to conditions (i.e., increased temperature or cell density) that up-regulate the expression of RpoS and OspC, normal induction of those proteins was observed. In addition, adding 20mM acetate or 20mM benzoate to the growth media of B. burgdorferi strain B31 DeltaackA induced the expression of RpoS and OspC. These data suggest that AcP (generated by AckA) is not directly involved in modulating the Rrp2-RpoN-RpoS regulatory pathway and that exogenous acetate or benzoate are triggering an acid stress response in B. burgdorferi. PMID- 26681320 TI - Peripheral loss of CD8(+) CD161(++) TCRValpha7.2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients. AB - BACKGROUND: Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. MATERIALS AND METHODS: We investigated the frequency of CD8(+) CD161(++) TCR Valpha7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. RESULTS: The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. CONCLUSIONS: Immune exhaustion and senescence of CD8(+) CD161(++) TCR Valpha7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression. PMID- 26681321 TI - Estimation of the Oxidative Stress and Molecular Damage Caused by 1-Butyl-3 Methylimidazolium Bromide Ionic Liquid in Zebrafish Livers. AB - The present study investigated the toxic effects of 1-butyl-3-methylimidazolium bromide ([C4 mim]Br) in zebrafish livers after exposure to 5-40 mg/L of [C4 mim]Br on days 7, 14, 21, and 28. The results showed that low levels of [C4 mim]Br exposure activated the superoxide dismutase (SOD) activity during early periods of exposure. However, high concentrations (20-40 mg/L) of [C4 mim]Br caused the inhibition of SOD, which, accordingly, led to excess reactive oxygen species and malondialdehyde. The present results indicate that [C4 mim]Br causes oxidative stress in the livers of both male and female zebrafish. Additionally, the DNA damage revealed that [C4 mim]Br has a genotoxic effect on zebrafish livers, even when the concentration of [C4 mim]Br is low (5 mg/L). The DNA damage was demonstrated by quantifying the DNA strand breakage. PMID- 26681322 TI - An Endosperm-Associated Cuticle Is Required for Arabidopsis Seed Viability, Dormancy and Early Control of Germination. AB - Cuticular layers and seeds are prominent plant adaptations to terrestrial life that appeared early and late during plant evolution, respectively. The cuticle is a waterproof film covering plant aerial organs preventing excessive water loss and protecting against biotic and abiotic stresses. Cutin, consisting of crosslinked fatty acid monomers, is the most abundant and studied cuticular component. Seeds are dry, metabolically inert structures promoting plant dispersal by keeping the plant embryo in an arrested protected state. In Arabidopsis thaliana seeds, the embryo is surrounded by a single cell endosperm layer itself surrounded by a seed coat layer, the testa. Whole genome analyses lead us to identify cutin biosynthesis genes as regulatory targets of the phytohormones gibberellins (GA) and abscisic acid (ABA) signaling pathways that control seed germination. Cutin-containing layers are present in seed coats of numerous species, including Arabidopsis, where they regulate permeability to outer compounds. However, the role of cutin in mature seed physiology and germination remains poorly understood. Here we identify in mature seeds a thick cuticular film covering the entire outer surface of the endosperm. This seed cuticle is defective in cutin-deficient bodyguard1 seeds, which is associated with alterations in endospermic permeability. Furthermore, mutants affected in cutin biosynthesis display low seed dormancy and viability levels, which correlates with higher levels of seed lipid oxidative stress. Upon seed imbibition cutin biosynthesis genes are essential to prevent endosperm cellular expansion and testa rupture in response to low GA synthesis. Taken together, our findings suggest that in the course of land plant evolution cuticular structures were co-opted to achieve key physiological seed properties. PMID- 26681323 TI - Characterization of phosphorus forms in lake macrophytes and algae by solution (31)P nuclear magnetic resonance spectroscopy. AB - Debris from aquatic macrophytes and algae are important recycling sources of phosphorus (P), which can result in continuing blooms of algae by recycling bioavailable P in the eutrophic lakes. However, knowledge of forms of P in aquatic macrophytes and algae and their contribution to internal loads of P in lakes is limited. Without such knowledge, it is difficult to develop appropriate strategies to remediate and or restore aquatic ecosystems that have become eutrophic. Therefore, in this work, P was extracted from six types of aquatic macrophytes and algae collected from Tai Lake of China and characterized by use of solution (31)P-nuclear magnetic resonance (NMR) spectroscopy. When extracted by 0.5 M NaOH-25 mM EDTA, extraction recovery of total P(TP) and organic P(Po) exceeded 90 %. Concentrations of Po in algae and aquatic macrophytes were 5552 mg kg(-1) and 1005 mg kg(-1) and accounted for 56.0 and 47.2 % of TP, respectively. When Po, including condensed P, was characterized by solution (31)P-NMR Po in algae included orthophosphate monoesters (79.8 %), pyrophosphate (18.2 %), and orthophosphate diester (2.0 %), and Po in aquatic macrophytes included orthophosphate monoesters (90.3 %), pyrophosphate (4.2 %), and orthophosphate diester (5.5 %). Additionally, orthophosphate monoesters in algal debris mainly included beta-glycerophosphate (44.1 %), alpha-glycerophosphate (13.5 %), and glucose 6-phosphate (13.5 %). Orthophosphate monoesters in aquatic macrophytes mainly included beta-glycerophosphate (27.9 %), alpha-glycerophosphate (24.6 %), and adenosine 5' monophosphate (8.2 %). Results derived from this study will be useful in better understanding nutrient cycling, relevant eutrophication processes, and pollution control for freshwater lakes. PMID- 26681324 TI - Effects of land use patterns on stream water quality: a case study of a small scale watershed in the Three Gorges Reservoir Area, China. AB - In this study, we have considered the relationship between the spatial configuration of land use and water quality in the Three Gorges Reservoir Area. Using land use types, landscape metrics, and long-term water quality data, as well as statistical and spatial analysis, we determined that most water quality parameters were negatively correlated with non-wood forest and urban areas but were strongly positively correlated with the proportion of forest area. Landscape indices such as patch density, contagion, and the Shannon diversity index were able to predict some water quality indicators, but the mean shape index was not significantly related to the proportions of farmland and water in the study area. Regression relationships were stronger in spring and fall than in summer, and relationships with nitrogen were stronger than those of the other water quality parameters (R(2) > 0.80) in all three seasons. Redundancy analysis showed that declining stream water quality was closely associated with configurations of urban, agricultural, and forest areas and with landscape fragmentation (PD) caused by urbanization and agricultural activities. Thus, a rational land use plan of adjusting the land use type, controlling landscape fragmentation, and increasing the proportion of forest area would help to achieve a healthier river ecosystem in the Three Gorges Reservoir Area (TGRA). PMID- 26681325 TI - Impact of maritime traffic on polycyclic aromatic hydrocarbons, metals and particulate matter in Venice air. AB - Harbours are important hubs for economic growth in both tourism and commercial activities. They are also an environmental burden being a source of atmospheric pollution often localized near cities and industrial complexes. The aim of this study is to quantify the relative contribution of maritime traffic and harbour activities to atmospheric pollutant concentration in the Venice lagoon. The impact of ship traffic was quantified on various pollutants that are not directly included in the current European legislation for shipping emission reduction: (i) gaseous and particulate PAHs; (ii) metals in PM10; and (iii) PM10 and PM2.5. All contributions were correlated with the tonnage of ships during the sampling periods and results were used to evaluate the impact of the European Directive 2005/33/EC on air quality in Venice comparing measurements taken before and after the application of the Directive (year 2010). The outcomes suggest that legislation on ship traffic, which focused on the issue of the emissions of sulphur oxides, could be an efficient method also to reduce the impact of shipping on primary particulate matter concentration; on the other hand, we did not observe a significant reduction in the contribution of ship traffic and harbour activities to particulate PAHs and metals. Graphical abstract Impact of maritime traffic on polycyclic aromatic hydrocarbons, metals and particulate matter and evaluation of the effect of an European Directive on air quality in Venice. PMID- 26681326 TI - Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism. AB - This is the first study reporting the presence of endogenous caffeine, theobromine, and theophylline in all organs of poplar plants. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used in order to evaluate the uptake, translocation, and metabolism of caffeine-(trimethyl (13)C) in Populus alba L. Villafranca clone grown in hydroponic conditions. We investigated the remediation of caffeine since it is one of the most widely consumed drugs and it is frequently detected in wastewater treatment plant effluents, surface water, and groundwater worldwide. Our results demonstrated that poplar can absorb and degrade exogenous caffeine without negative effects on plant health. Data showed that concentrations of all endogenous compounds varied depending on caffeine-(trimethyl-(13)C) treatments. In particular, in control conditions, endogenous caffeine, theobromine, and theophylline were mainly distributed in roots. On the other hand, once caffeine-(trimethyl-(13)C) was provided, this compound and its dimethy-(13)C metabolites are mainly localized at leaf level. In conclusion, our results support the possible use of Villafranca clone in association with other water treatment systems in order to complete the process of caffeine remediation. PMID- 26681327 TI - A study on identification of bacteria in environmental samples using single-cell Raman spectroscopy: feasibility and reference libraries. AB - We report on our recent efforts towards identifying bacteria in environmental samples by means of Raman spectroscopy. We established a database of Raman spectra from bacteria submitted to various environmental conditions. This dataset was used to verify that Raman typing is possible from measurements performed in non-ideal conditions. Starting from the same dataset, we then varied the phenotype and matrix diversity content included in the reference library used to train the statistical model. The results show that it is possible to obtain models with an extended coverage of spectral variabilities, compared to environment-specific models trained on spectra from a restricted set of conditions. Broad coverage models are desirable for environmental samples since the exact conditions of the bacteria cannot be controlled. PMID- 26681328 TI - Environmental impact and potential utilization of historical Cu-Fe-Co slags. AB - Historical slags from the past Fe and Cu-Co production were investigated in order to evaluate either their potential for utilization or their long-term environmental risk for unsupervised old smelting areas. Here, we studied ferrous slags produced during the recovery of Fe from siderite-Cu ores in Slovakia and two different types of non-ferrous slags produced during the recovery of Cu and Co from Kupferschiefer ores in Germany. The glassy character, rare occurrence of primary silicate phases, and the lack of secondary phases in Cu slags indicate their stability for a prolonged period of time. Electron microprobe analytical work showed that the metals and metalloids (Cu, Co, Fe, Zn, Pb, As) are largely encased in droplets of matte and metal alloys and remain protected by the glassy matrix with its low weathering rate. Fe and Co slags are composed of high temperature silicates such as wollastonite, cristobalite, as well as olivine, feldspar, quartz, leucite, pyroxene, and pyroxenoids. The presence of secondary phases attests to a certain degree metal release owing to weathering. Assuming minimal contents of metals in slags after a treatment with dilute H2SO4, slags could be used as pozzolanas for addition to cement. PMID- 26681329 TI - The role of supplemental ultraviolet-B radiation in altering the metabolite profile, essential oil content and composition, and free radical scavenging activities of Coleus forskohlii, an indigenous medicinal plant. AB - The effects of supplemental ultraviolet-B (s-UV-B; 3.6 kJ m(-2) day(-1) above ambient) radiation were investigated on plant metabolite profile, essential oil content and composition, and free radical scavenging capacities of methanolic extracts of Coleus forskohlii (an indigenous medicinal plant) grown under field conditions. Essential oil was isolated using hydrodistillation technique while alterations in metabolite profile and oil composition were determined via gas chromatography-mass spectroscopy (GC-MS). Leaf and root methanolic extracts were investigated via various in vitro assays for their DPPH radical-, superoxide radical-, hydrogen peroxide-, hydroxyl radical-, and nitric oxide radical scavenging activities, ferrous ion chelating activity, and reducing power. Phytochemical analysis revealed the presence of alkaloids, anthocyanins, coumarins, flavonoids, glycosides, phenols, saponins, steroids, tannins, and terpenoids. Oil content was found to be reduced (by ~7 %) in supplemental UV-B (s UV-B) treated plants; the composition of the plant extracts as well as essential oil was also considerably altered. Methanolic extracts from treated plant organs showed more potency as free radical scavengers (their EC50 values being lower than their respective controls). Anomalies were observed in Fe(2+) chelating activity for both leaves and roots. The present study concludes that s-UV-B adversely affects oil content in C. forskohlii and also alters the composition and contents of metabolites in both plant extracts and oil. The results also denote that s-UV-B treated plant organs might be more effective in safeguarding against oxidative stress, though further studies are required to authenticate these findings. PMID- 26681330 TI - Mineralogy and geochemistry of efflorescent minerals on mine tailings and their potential impact on water chemistry. AB - In the gold mining Witwatersrand Basin of South Africa, efflorescent mineral crusts are a common occurrence on and nearby tailings dumps during the dry season. The crusts are readily soluble and generate acidic, metal- and sulphate rich solutions on dissolution. In this study, the metal content of efflorescent crusts at an abandoned gold mine tailings dump was used to characterise surface and groundwater discharges from the site. Geochemical modelling of the pH of the solution resulting from the dissolution of the crusts was used to better understand the crusts' potential impact on water chemistry. The study involved two approaches: (i) conducting leaching experiments on oxidised and unoxidised tailings using artificial rainwater and dilute sulphuric acid and correlating the composition of crusts to these leachates and (ii) modelling the dissolution of the crusts in order to gain insight into their mineralogy and their potential impact on receiving waters. The findings suggested that there were two chemically distinct discharges from the site, namely an aluminium- and magnesium-rich surface water plume and an iron-rich groundwater plume. The first plume was observed to originate from the oxidised tailings following leaching with rainwater while the second plume originated from the underlying unoxidised tailings with leaching by sulphuric acid. Both groups of minerals forming from the respective plumes were found to significantly lower the pH of the receiving water with simulations of their dissolution found to be within 0.2 pH units of experimental values. It was observed that metals in a low abundance within the crust (for example, iron) had a stronger influence on the pH of the resulting solutions than metals in a greater abundance (aluminium or magnesium). Techniques such as powder X-ray diffraction (PXRD) and in situ mineral determination techniques such as remote sensing can effectively determine the dominant mineralogy. However, the minerals or metals incorporated through solid solution into bulk mineralogy that dominates the chemistry of the solutions upon their dissolution may occur in minor quantities that can only be predicted using chemical analysis. Their mineralogy can be predicted using geochemical modelling and can provide a set of hypothetical minerals that upon dissolution yield a solution similar to that of the actual crusts. This realisation has a bearing on decision-making such as in risk assessment and designing pollutant mitigation strategies. PMID- 26681331 TI - Direct mineral carbonation of steelmaking slag for CO2 sequestration at room temperature. AB - Rapid increase of CO2 concentration in the atmosphere has forced the international community towards adopting actions to restrain from the impacts of climate change. Moreover, in India, the dependence on fossil fuels is projected to increase in the future, implying the necessity of capturing CO2 in a safe manner. Alkaline solid wastes can be utilized for CO2 sequestration by which its disposal issues in the country could also be met. The present work focuses to study direct mineral carbonation of steelmaking slag (SS) at room temperature and low-pressure conditions (<10 bar). Direct mineral carbonation of SS was carried out in a batch reactor with pure CO2 gas. The process parameters that may influence the carbonation of SS, namely, CO2 gas pressure, liquid to solid ratio (L/S) and reaction time were also studied. The results showed that maximum sequestration of SS was attained in the aqueous route with a capacity of 82 g of CO2/kg (6 bar, L/S ratio of 10 and 3 h). In the gas-solid route, maximum sequestration capacity of about 11.1 g of CO2/kg of SS (3 bar and 3 h) was achieved indicating that aqueous route is the better one under the conditions studied. These findings demonstrate that SS is a promising resource and this approach could be further developed and used for CO2 sequestration in the country. The carbonation process was evidenced using FT-IR, XRD, SEM and TG analysis. PMID- 26681332 TI - 'The End of Sitting': An Empirical Study on Working in an Office of the Future. AB - BACKGROUND: Inspired by recent findings that prolonged sitting has detrimental health effects, Rietveld Architecture Art Affordances (RAAAF) and visual artist Barbara Visser designed a working environment without chairs and desks. This environment, which they called The End of Sitting, is a sculpture whose surfaces afford working in several non-sitting postures (e.g. lying, standing, leaning). OBJECTIVE: In the present study, it was tested how people use and experience The End of Sitting. Eighteen participants were to work in this environment and in a conventional office with chairs and desks, and the participants' activities, postures, and locations in each working environment were monitored. In addition, participants' experiences with working in the offices were measured with a questionnaire. RESULTS: It was found that 83 % of participants worked in more than one non-sitting posture in The End of Sitting. All these participants also changed location in this working environment. On the other hand, in the conventional office all but one participant sat on a chair at a desk during the entire work session. On average, participants reported that The End of Sitting supported their well-being more than the conventional office. Participants also felt more energetic after working in The End of Sitting. No differences between the working environments were found in reported concentration levels and satisfaction with the created product. CONCLUSION: The End of Sitting is a potential alternative working environment that deserves to be examined in more detail. PMID- 26681333 TI - Vascularized middle turbinate flap for the endoscopic endonasal reconstruction of the anterior olfactory groove. AB - A vascularized middle turbinate flap (MTF) might be useful in the repair of lesions in the anterior olfactory groove. The sizes of the MTF and inferior turbinate flap (ITF) and these distances up to the frontal base were analyzed by computed tomography (CT) using a picture archiving and communication system (PACS) in 20 patients. The minimum flap measurement to reconstruct the skull base was defined as the distance from the basal plate to the medial slope or lateral slope edge of the MTF and the ITF on the coronal view. Next, we reviewed clinical data from three patients with dural deficits who underwent endoscopic vascularized MTF reconstruction. The distance to the frontal base from the ITF was significantly longer than that from the MTF. The minimum length of the MTF measured by coronal CT was similar to the distance to the frontal base. In contrast, the minimum length of the ITF was shorter than the distance to the frontal base. These results suggest that the MTF might be superior to the ITF for coverage of the anterior frontal base. Three patients who underwent MTF reconstruction for a defect in the anterior olfactory groove had good outcomes and no complications. The MTF is a good option for reconstruction of defects in the anterior part of the olfactory groove. PMID- 26681334 TI - Isolated double-orifice mitral valve: a case report. AB - BACKGROUND: Double-orifice mitral valve is an extremely rare cardiac anomaly possibly originating from insufficient endocardial fusion in embryogenesis. Severe concomitant cardiac anomalies and malfunction of the valve usually lead to an early diagnosis in childhood. Therefore the prevalence of isolated double orifice mitral valve in adulthood is not known. CASE PRESENTATION: We present the case of a 63 years old, female Caucasian patient with isolated double-orifice mitral valve diagnosed in routine echocardiographic evaluation after chemotherapy presenting without clinical symptoms. CONCLUSION: Trans-thoracic echocardiography is a suitable modality to diagnose and further assess anatomical and functional properties of the anomaly. In the presence of double-orifice mitral valve concomitant cardiac anomalies and valvular stenosis or regurgitation must be excluded. If an isolated double-orifice mitral valve with no functional abnormalities is present, no further follow-up is necessary. PMID- 26681335 TI - Obtaining long 16S rDNA sequences using multiple primers and its application on dioxin-containing samples. AB - BACKGROUND: Next-generation sequencing (NGS) technology has transformed metagenomics because the high-throughput data allow an in-depth exploration of a complex microbial community. However, accurate species identification with NGS data is challenging because NGS sequences are relatively short. Assembling 16S rDNA segments into longer sequences has been proposed for improving species identification. Current approaches, however, either suffer from amplification bias due to one single primer or insufficient 16S rDNA reads in whole genome sequencing data. RESULTS: Multiple primers were used to amplify different 16S rDNA segments for 454 sequencing, followed by 454 read classification and assembly. This permitted targeted sequencing while reducing primer bias. For test samples containing four known bacteria, accurate and near full-length 16S rDNAs of three known bacteria were obtained. For real soil and sediment samples containing dioxins in various concentrations, 16S rDNA sequences were lengthened by 50% for about half of the non-rare microbes, and 16S rDNAs of several microbes reached more than 1000 bp. In addition, reduced primer bias using multiple primers was illustrated. CONCLUSIONS: A new experimental and computational pipeline for obtaining long 16S rDNA sequences was proposed. The capability of the pipeline was validated on test samples and illustrated on real samples. For dioxin-containing samples, the pipeline revealed several microbes suitable for future studies of dioxin chemistry. PMID- 26681336 TI - Anomalous Tunnel Magnetoresistance and Spin Transfer Torque in Magnetic Tunnel Junctions with Embedded Nanoparticles. AB - The tunnel magnetoresistance (TMR) in the magnetic tunnel junction (MTJ) with embedded nanoparticles (NPs) was calculated in range of the quantum-ballistic model. The simulation was performed for electron tunneling through the insulating layer with embedded magnetic and non-magnetic NPs within the approach of the double barrier subsystem connected in parallel to the single barrier one. This model can be applied for both MTJs with in-plane magnetization and perpendicular one. We also calculated the in-plane component of the spin transfer torque (STT) versus the applied voltage in MTJs with magnetic NPs and determined that its value can be much larger than in single barrier system (SBS) for the same tunneling thickness. The reported simulation reproduces experimental data of the TMR suppression and peak-like TMR anomalies at low voltages available in leterature. PMID- 26681337 TI - Alpha-fetoprotein normalization as a prognostic surrogate in small hepatocellular carcinoma after stereotactic body radiotherapy: a propensity score matching analysis. AB - BACKGROUND: To assess the significance of alpha-fetoprotein (AFP) normalization as a prognostic surrogate after stereotactic body radiotherapy (SBRT) for patients with small hepatocellular carcinoma (HCC). METHODS: Patients who underwent SBRT for primary or recurrent HCC were registered and a database thereof was retrospectively reviewed. Among 165 total registered patients, 77 patients were selected who satisfied the following criteria: (1) their AFP levels were > 20 ng/mL before SBRT, and (2) their AFP levels were checked within three months after SBRT. Propensity score based matching analysis was performed to minimize potential confounding bias. AFP normalization was defined as a reduction of AFP level to <= 20 ng/mL. Overall survival (OS) and progression-free survival (PFS) curves were estimated by the Kaplan-Meier method. RESULTS: Thirty-seven (48.1 %) patients displayed AFP normalization (normalized group), while 40 (51.9 %) patients comprised the non-normalized group. The OS rates at 3-year were 62.0 % and 44.0 % (p = 0.023), and the PFS rates at 3-year were 27.9 % and 12.0 % (p = 0.019), in the normalized and non-normalized groups, respectively. Local control rates were 97.2 % in the normalized group and 94.7 % in the non-normalized group at three years (p = 0.579). In the propensity score matching cohort (25 pairs), OS and PFS were significantly longer in the normalized group than in the non normalized group (p = 0.017 and 0.049, respectively). The local control rates were 100 % in both matched groups. CONCLUSIONS: AFP normalization within three months after SBRT is a prognostic surrogate for OS and PFS in patients with small HCC. AFP monitoring should be considered a useful tool for HCC patients with an elevated AFP level before SBRT. PMID- 26681338 TI - Neck Circumference and Incidence of Diabetes Mellitus over 10 Years in the Korean Genome and Epidemiology Study (KoGES). AB - Neck circumference, a proxy for upper-body fat, may be a unique fat depot that indicates metabolic risk beyond whole body fat. We investigated whether neck circumference is associated with development of diabetes mellitus (DM) in a subset of data with Korean Genome and Epidemiology Study (n = 3521, age range = 42-71 years). Nondiabetic subjects at the baseline were categorized into 4 groups (Q1-Q4) according to their neck circumference. Parameters related with beta-cell function and insulin resistance including Epworth sleepiness scale and snoring habit were examined. The development of DM was confirmed biannually based on a 75 g oral glucose tolerance test. Over the 10 years, 2623 (74.5%) among 3521 subjects were followed-up. Among them, 632 (24.1%) developed DM. The incidence of DM increased from 17.6% in Q1 to 18.2% in Q2, to 25.4% in Q3, and to 36.0% in Q4 (P < 0.001). After adjusting for most risk factors related with DM, the relative risks of DM development were 0.989 (95% confidence interval, 0.638-1.578), 1.660 (1.025-2.687), and 1.746 (1.037-2.942) in men and 0.939 (0.540-1.769), 1.518 (0.808-2.853), and 2.077 (1.068-4.038) in women in Q2, Q3, and Q4, respectively when compared to Q1. This finding indicates negative impact from large neck circumference in the development of DM. PMID- 26681339 TI - Iron oxide nanoparticle-mediated hyperthermia stimulates dispersal in bacterial biofilms and enhances antibiotic efficacy. AB - The dispersal phase that completes the biofilm lifecycle is of particular interest for its potential to remove recalcitrant, antimicrobial tolerant biofilm infections. Here we found that temperature is a cue for biofilm dispersal and a rise by 5 degrees C or more can induce the detachment of Pseudomonas aeruginosa biofilms. Temperature upshifts were found to decrease biofilm biomass and increase the number of viable freely suspended cells. The dispersal response appeared to involve the secondary messenger cyclic di-GMP, which is central to a genetic network governing motile to sessile transitions in bacteria. Furthermore, we used poly((oligo(ethylene glycol) methyl ether acrylate)-block poly(monoacryloxy ethyl phosphate)-stabilized iron oxide nanoparticles (POEGA-b PMAEP@IONPs) to induce local hyperthermia in established biofilms upon exposure to a magnetic field. POEGA-b-PMAEP@IONPs were non-toxic to bacteria and when heated induced the detachment of biofilm cells. Finally, combined treatments of POEGA-b-PMAEP@IONPs and the antibiotic gentamicin reduced by 2-log the number of colony-forming units in both biofilm and planktonic phases after 20 min, which represent a 3.2- and 4.1-fold increase in the efficacy against planktonic and biofilm cells, respectively, compared to gentamicin alone. The use of iron oxide nanoparticles to disperse biofilms may find broad applications across a range of clinical and industrial settings. PMID- 26681340 TI - Determining the familial risk distribution of colorectal cancer: a data mining approach. AB - This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer. PMID- 26681343 TI - Cover story: call to action figures. PMID- 26681342 TI - Use of a bioartificial dermal regeneration template for skin restoration in combat casualty injuries. AB - Military personnel who survive combat injuries frequently have large soft tissue wounds complicated by concomitant injuries and contamination. These devastating wounds present a therapeutic challenge to not only restore the protective skin barrier but also to preserve tendon and muscle excursion, provide protective padding around nerves and restore adequate joint motion. Accordingly, regenerative medicine modalities that can accomplish these goals are of great interest. The use of bioartificial dermal regeneration templates (DRT), such as Integra DRT (Integra Lifesciences Corporation, Plainsboro, NJ, USA), in the management of complex soft tissue injuries has an important role in the reconstruction of war wounds. These DRTs provide initial wound coverage and help establish a well-vascularized wound bed suitable for definitive soft tissue coverage. PMID- 26681341 TI - Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma. AB - BACKGROUND: Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined. METHODS: We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total protein-albumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors. RESULTS: The median (IQR) preoperative AGR was 1.50 (1.30-1.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR >= 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively). CONCLUSIONS: Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens. PMID- 26681344 TI - The complete mitochondrial genome of Pseudorhombus dupliocellatus (Pleuronectiformes: Paralichthyidae). AB - The Pseudorhombus dupliocellatus belongs to family Paralichthyidae of Pleuronectiformes. In this study, the complete mitochondrial genome of P. dupliocellatus is determined and described. The mitogenome is 16 621 bp in length and consists of 13 protein-coding genes, 22 tRNAs, 2 rRNAs, a control region, and a L-strand replication origin. The arrangement of the mitogenome is identical to that of the typical teleost. The overall base composition is 26.9%, 25.3%, 31.0%, and 16.8% for A, T, C, and G, respectively, with a slight bias on A+T content (52.2%). The phylogenetic tree of 13 species all in Pleuronectiformes demonstrated that P. dupliocellatus, as well as the other Paralichthyidae fishes containing Paralichthys olivaceus and Pseudorhombus cinnamoneus, clustered in a clade and had a closer relationship with Pleuronectidae species than Bothidae ones. This study is expected to contributing to the systematic evolution of Paralichthyidae and further Pleuronectiformes. PMID- 26681345 TI - Fluctuating, warm temperatures decrease the effect of a key floral repressor on flowering time in Arabidopsis thaliana. AB - The genetic basis of growth and development is often studied in constant laboratory environments; however, the environmental conditions that organisms experience in nature are often much more dynamic. We examined how daily temperature fluctuations, average temperature, day length and vernalization influence the flowering time of 59 genotypes of Arabidopsis thaliana with allelic perturbations known to affect flowering time. For a subset of genotypes, we also assessed treatment effects on morphology and growth. We identified 17 genotypes, many of which have high levels of the floral repressor FLOWERING LOCUS C (FLC), that bolted dramatically earlier in fluctuating - as opposed to constant - warm temperatures (mean = 22 degrees C). This acceleration was not caused by transient VERNALIZATION INSENSITIVE 3-mediated vernalization, differential growth rates or exposure to high temperatures, and was not apparent when the average temperature was cool (mean = 12 degrees C). Further, in constant temperatures, contrary to physiological expectations, these genotypes flowered more rapidly in cool than in warm environments. Fluctuating temperatures often reversed these responses, restoring faster bolting in warm conditions. Independently of bolting time, warm fluctuating temperature profiles also caused morphological changes associated with shade avoidance or 'high-temperature' phenotypes. Our results suggest that previous studies have overestimated the effect of the floral repressor FLC on flowering time by using constant temperature laboratory conditions. PMID- 26681346 TI - The effect of micro-electric current and other activation techniques on dissolution abilities of sodium hypochlorite in bovine tissues. AB - BACKGROUND: The aim of the study was to evaluate the effects of micro-electric current on sodium hypochlorite's (NaOCl's) tissue-dissolution abilities, compared with other activation methods, including sonic, ultrasonic, pipetting, and temperature. METHODS: Bovine muscle tissues (n = 154) with standard sizes and weights were prepared and divided into two temperature groups: room temperature and 45 degrees C. Each temperature group was divided into seven sub-groups by activation methods: D = distilled water (-control); NaOCl = 5.25 % passive NaOCl (+ control); P = 5.25 % NaOCl with pipetting; SA = 5.25 % NaOCl with sonic activation; UA = 5.25 % NaOCl with ultrasonic activation; E-NaOCl = 5.25 % NaOCl with micro-electric current; and E-NaOCl + P = 5.25 % NaOCl with micro-electric current and pipetting. Specimens were weighed before and after treatment. Average, standard deviation, minimum, maximum, and median were calculated for each group. Resulting data were analyzed statistically using multi-way ANOVA and Tukey HSD tests. The level of the alpha-type error was set at < 0.05. RESULTS: At room temperature, the E-NaOCl + P group dissolved the highest amount of tissue (p < 0.05), and the UA, SA, and P groups dissolved significantly higher amounts of tissue than did the positive control or E-NaOCl groups (p < 0.05). At 45 degrees C, there was no significant difference between the SA and E-NaOCl groups (p > 0.05), and the E-NaOCl + P group dissolved a higher amount of tissue than any other group (p < 0.05). CONCLUSIONS: Using NaOCl with micro-electric current can improve the tissue-dissolving ability of the solution. In addition, this method can be combined with additional techniques, such as heating and/or pipetting, to achieve a synergistic effect of NaOCl on tissue dissolution. PMID- 26681347 TI - Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments. AB - OBJECTIVES: The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. METHODS: We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. RESULTS: The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. CONCLUSION: On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed. PMID- 26681348 TI - The "omega" jejunostomy tube: A preferred alternative for postpyloric feeding access. AB - AIM: We present our technique for construction of the "Omega Jejunostomy" (OJ), a novel method of postpyloric feeding using a pouched-jejunal loop capable of accommodating a balloon gastrostomy button. We describe potential indications for the procedure and outcomes in a complex patient population. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent an OJ at our institution between 2005 and 2014. Primary outcomes include operating time, length of hospital stay, time to feeding goals, and postoperative complications. RESULTS: We identified 12 children (6 males) with multiple comorbidities who underwent OJ procedures. The median age at surgery was 11years (range 3months 23years). Eleven patients had failed previous alternative feeding access or antireflux procedures. All patients eventually reached their feeding goals. Eight were at goal feeds in <10days. Two achieved goal feeds <1month, one <4months, and one within 7months. There was one OJ failure because of fistula formation requiring surgical revision, and one child was treated successfully but died of unrelated causes. Four children eventually transitioned to PO or G-tube feeds, and six were tolerating feeds via OJ at last follow-up (8-74months). CONCLUSIONS: OJ provides a durable alternative to gastrojejunostomy tube for patients who are poor candidates for or have failed Nissen fundoplication. It is technically easier to perform than a gastroesophageal disconnect procedure, has minimal surgical comorbidities, and can provide durable feeding access and achievement of goal feeds in a complex and refractory patient subset. PMID- 26681349 TI - A Cost-Effectiveness Analysis of the Swedish Universal Parenting Program All Children in Focus. AB - OBJECTIVE: There are few health economic evaluations of parenting programs with quality-adjusted life-years (QALYs) as the outcome measure. The objective of this study was, therefore, to conduct a cost-effectiveness analysis of the universal parenting program All Children in Focus (ABC). The goals were to estimate the costs of program implementation, investigate the health effects of the program, and examine its cost-effectiveness. METHODS: A cost-effectiveness analysis was conducted. Costs included setup costs and operating costs. A parent proxy Visual Analog Scale was used to measure QALYs in children, whereas the General Health Questionnaire-12 was used for parents. A societal perspective was adopted, and the incremental cost-effectiveness ratio was calculated. To account for uncertainty in the estimate, the probability of cost-effectiveness was investigated, and sensitivity analyses were used to account for the uncertainty in cost data. RESULTS: The cost was ? 326.3 per parent, of which ? 53.7 represented setup costs under the assumption that group leaders on average run 10 groups, and ? 272.6 was the operating costs. For health effects, the QALY gain was 0.0042 per child and 0.0027 per parent. These gains resulted in an incremental cost-effectiveness ratio for the base case of ? 47 290 per gained QALY. The sensitivity analyses resulted in ratios from ? 41 739 to ? 55 072. With the common Swedish threshold value of ? 55 000 per QALY, the probability of the ABC program being cost-effective was 50.8 percent. CONCLUSION: Our analysis of the ABC program demonstrates cost-effectiveness ratios below or just above the QALY threshold in Sweden. However, due to great uncertainty about the data, the health economic rationale for implementation should be further studied considering a longer time perspective, effects on siblings, and validated measuring techniques, before full scale implementation. PMID- 26681350 TI - Optimization and effect of dairy industrial waste as media components in the production of hyaluronic acid by Streptococcus thermophilus. AB - Hyaluronic acid (HA) production using a dairy industrial waste is a more cost efficient strategy than using an expensive synthetic medium. In this study, we investigated the production of HA using Streptococcus thermophilus under shake flask conditions using dairy industrial waste as nutritional supplements, namely whey permeate (WP) and whey protein hydrolysate (WPH). Preliminary screening using Plackett-Burman design exhibited WP, WPH, initial pH, and inoculum size as significant factors influencing HA titer. Response surface methodology design of four factors was formulated at three levels for enhanced production of HA. Shake flask HA fermentation by S. thermophilus was performed under global optimized process conditions and the optimal HA titer (342.93 mg L(-1)) corroborates with Box-Behnken design prediction. The molecular weight of HA was elucidated as 9.22 9.46 kDa. The ultralow-molecular weight HA reported in this study has a potential role in drug and gene delivery applications. PMID- 26681351 TI - Guideline summary review: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis. AB - BACKGROUND CONTEXT: The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. The NASS guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). PURPOSE: The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. STUDY DESIGN: A systematic review of clinical studies relevant to degenerative spondylolisthesis was carried out. METHODS: This NASS spondyolisthesis guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members used the NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence based recommendations and incorporate expert opinion when necessary. The draft guidelines were submitted to an internal peer review process and ultimately approved by the NASS Board of Directors. Upon publication, the Degenerative Lumbar Spondylolisthesis guideline was accepted into the NGC and will be updated approximately every 5 years. RESULTS: Twenty-seven clinical questions were addressed in this guideline update, including 15 clinical questions from the original guideline and 12 new clinical questions. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. Twenty-one new or updated recommendations or consensus statements were issued and 13 recommendations or consensus statements were maintained from the original guideline. CONCLUSIONS: The clinical guideline was created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with degenerative lumbar spondylolisthesis. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flow chart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/Pages/ResearchClinicalCare/QualityImprovement/ClinicalGuide ines.aspx and will remain updated on a timely schedule. PMID- 26681353 TI - Synovial sarcoma with multiple vertebrae metastases causing multilevel thoracic spinal cord compressions. PMID- 26681352 TI - Dimensional changes of the neuroforamina in subaxial cervical spine during in vivo dynamic flexion-extension. AB - BACKGROUND CONTEXT: Neuroforaminal stenosis is one of the key factors causing clinical symptoms in patients with cervical radiculopathy. Previous quantitative studies on the neuroforaminal dimensions have focused on measurements in a static position. Little is known about dimensional changes of the neuroforamina in the cervical spine during functional dynamic neck motion under physiological loading conditions. PURPOSE: This study aimed to investigate the in vivo dimensional changes of the neuroforamina in human cervical spine (C3-C7) during dynamic flexion-extension neck motion. STUDY DESIGN: A case-control study was carried out. METHODS: Ten asymptomatic subjects were recruited for this study. The cervical spine of each subject underwent magnetic resonance image scanning for construction of three-dimensional (3-D) vertebrae models from C3 to C7. The cervical spine was then imaged using a dual fluoroscopic system while the subject performed a dynamic flexion-extension neck motion in a sitting position. The 3-D vertebral models and the fluoroscopic images were used to reproduce the in vivo vertebral motion. The dimensions (area, height, and width) were measured for each cervical neuroforamen (C3/C4, C4/C5, C5/C6, and C6/C7) in the following functional positions: neutral position, maximal flexion, and maximal extension. Repeated measures analysis of variance and post hoc analysis were used to examine the differences between levels and positions. RESULTS: Compared with the neutral position, almost all dimensional parameters (area, height, and width) of the subaxial cervical neuroforamina decreased in extension and increased in flexion, except the neuroforaminal area at C5/C6 (p=.07), and the neuroforaminal height at C6/C7 (p=.05) remained relatively constant from neutral to extension. When comparisons of the overall change fromextension to flexion were made between segments, the overall changes of the neuroforaminal area and height revealed no significant differences between segments, and the width overall change of the upper levels (C3/C4 and C4/C5) was significantly greater than the lower levels (C5/C6 and C6/C7) (p<.01). CONCLUSIONS: The dimensional changes of the cervical neuroforamina showed segment-dependent characteristics during the dynamic flexion extension. These data may have implications for diagnosis and treatment of patients with cervical radiculopathy. PMID- 26681354 TI - Spinal arachnoid cyst as a cause of isolated, progressive, bilateral C5-C6 radiculopathy. PMID- 26681355 TI - A case of spontaneous atlantoaxial facet fusion following posterior distraction reduction of basilar invagination. PMID- 26681356 TI - Fossil nutlets of Boraginaceae from the continental Eocene of Hamada of Meridja (southwestern Algeria): The first fossil of the Borage family in Africa. AB - PREMISE OF THE STUDY: The Paleogene deposits of the Hamada of Meridja, southwestern Algeria, are currently dated as lower-to-middle Eocene in age based on fossil gastropods and charophytes. Here we report the presence of fruits that can be assigned to the Boraginaceae s.str., apparently representing the first fossil record for this family in Africa, shedding new light on the historical biogeography of this group. METHODS: Microscopic studies of the fossil nutlets were carried out and compared to extant Boraginaceae nutlets, and to types reported in the literature for this family. KEY RESULTS: The fossils are strikingly similar in general size and morphology, particularly in the finer details of the attachment scar and ornamentation, to nutlets of extant representatives of the Boraginaceae tribe Echiochileae, and especially the genus Ogastemma. We believe that these nutlets represent an extinct member of this lineage. CONCLUSIONS: The Ogastemma-like fossils indicate that the Echiochileae, which are most diverse in northern Africa and southwestern Asia, have a long history in this region, dating back to the Eocene. This tribe corresponds to the basal-most clade in Boraginaceae s.str., and the fossils described here agree well with an assumed African origin of the family and the Boraginales I, providing an important additional calibration point for dating the phylogenies of this clade. PMID- 26681357 TI - Data linkage between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to assess workplace physical activity, sedentary behaviors, and emotional stressors during pregnancy. AB - BACKGROUND: Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. METHODS: Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother's primary job to the Occupational Information Network Version 9.0. RESULTS: The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for >=75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. CONCLUSIONS: Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. PMID- 26681358 TI - Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits. AB - BACKGROUND: Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). RESULTS: During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). CONCLUSION: Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+. PMID- 26681359 TI - Viral suppression in adolescents on antiretroviral treatment: review of the literature and critical appraisal of methodological challenges. AB - OBJECTIVE: Medication adherence is often suboptimal for adolescents with HIV, and establishing correct weight-based antiretroviral therapy dosing is difficult, contributing to virological failure. This review aimed to determine the proportion of adolescents achieving virological suppression after initiating ART. METHODS: MEDLINE, EMBASE and Web of Science databases were searched. Studies published between January 2004 and September 2014 including >=50 adolescents taking ART and reporting on the proportion of virological suppressed participants were included. RESULTS: From a total of 5316 potentially relevant citations, 20 studies were included. Only eight studies reported the proportion of adolescents that were virologically suppressed at a specified time point. The proportion of adolescents with virological suppression at 12 months ranged from 27 to 89%. CONCLUSION: Adolescent achievement of HIV virological suppression was highly variable. Improved reporting of virological outcomes from a wider range of settings is required to support efforts to improve HIV care and treatment for adolescents. PMID- 26681361 TI - Co-existence of glioblastoma and cerebral aneurysm. PMID- 26681362 TI - End-of-Life Care for Undocumented Immigrants With Advanced Cancer: Documenting the Undocumented. AB - There are approximately 11.1 million undocumented immigrants in the United States, with a majority being Latino. Cancer is now the leading cause of death in Latinos. There is little research guiding providers on how to deliver optimal end of-life care in this population. We describe a case of an undocumented Latino patient with advanced cancer, and provide a review of the literature on end-of life care in undocumented immigrants. Our patient encountered many challenges as he navigated through the healthcare system in the last months of life. These included delayed diagnosis, limited social support, financial issues, fear of deportation, and language and cultural barriers, which resulted in significant physical and psychological distress. Within the undocumented patient population, there is often a lack of advance care planning, prognostic understanding, mistrust, religious practices, and cultural beliefs that may affect decision making. Given the growing number of undocumented immigrants in the United States, it is important for clinicians and policy makers to have a better understanding of the issues surrounding end-of-life care for undocumented immigrants, and work together to improve the quality of life and quality of end-of-life care for these disadvantaged individuals. PMID- 26681364 TI - Resource recovery from landfill leachate using bioelectrochemical systems: Opportunities, challenges, and perspectives. AB - Landfill leachate has recently been investigated as a substrate for bioelectrochemical systems (BES) for electricity generation. While BES treatment of leachate is effective, the unique feature of bioelectricity generation in BES creates opportunities for resource recovery from leachate. The organic compounds in leachate can be directly converted to electrical energy through microbial interaction with solid electron acceptors/donors. Nutrient such as ammonia can be recovered via ammonium migration driven by electricity generation and ammonium conversion to ammonia in a high-pH condition that is a result of cathode reduction reaction. Metals in leachate may also be recovered, but the recovery is affected by their concentrations and values. Through integrating membrane process, especially forward osmosis, BES can recover high-quality water from leachate for applications in landscaping, agricultural irrigation or direct discharge. This review paper discusses the opportunities, challenges, and perspectives of resource recovery from landfill leachate by using BES. PMID- 26681363 TI - Long-Term Ozone Exposure Increases the Risk of Developing the Acute Respiratory Distress Syndrome. AB - RATIONALE: The contribution of air pollution to the risk of acute respiratory distress syndrome (ARDS) is unknown. METHODS: We studied 1,558 critically ill patients enrolled in a prospective observational study at a tertiary medical center who lived less than 50 km from an air quality monitor and had an ARDS risk factor. Pollutant exposures (ozone, NO2, SO2, particulate matter < 2.5 MUm, particulate matter < 10 MUm) were assessed by weighted average of daily levels from the closest monitors for the prior 3 years. Associations between pollutant exposure and ARDS risk were evaluated by logistic regression controlling for age, race, sex, smoking, alcohol, insurance status, rural versus urban residence, distance to study hospital, and Acute Physiology and Chronic Health Evaluation II. MEASUREMENTS AND MAIN RESULTS: The incidence of ARDS increased with increasing ozone exposure: 28% in the lowest exposure quartile versus 32, 40, and 42% in the second, third, and fourth quartiles (P < 0.001). In a logistic regression model controlling for potential confounders, ozone exposure was associated with risk of ARDS in the entire cohort (odds ratio, 1.58 [95% confidence interval, 1.27-1.96]) and more strongly associated in the subgroup with trauma as their ARDS risk factor (odds ratio, 2.26 [95% confidence interval, 1.46-3.50]). There was a strong interaction between ozone exposure and current smoking status (P = 0.007). NO2 exposure was also associated with ARDS but not independently of ozone exposure. SO2, particulate matter less than 2.5 MUm, and particulate matter less than 10 MUm were not associated with ARDS. CONCLUSIONS: Long-term ozone exposure is associated with development of ARDS in at-risk critically ill patients, particularly in trauma patients and current smokers. Ozone exposure may represent a previously unrecognized environmental risk factor for ARDS. PMID- 26681365 TI - N-Nitrosamine-{cis-Re[CO]2}(2+) cobalamin conjugates as mixed CO/NO-releasing molecules. AB - Mixed CO/NO-releasing molecules were prepared by conjugation of the 17-electron rhenium dicarbonyl cis-[Re(CO)2Br4](2-) complex to N-nitrosamine modified cyanocobalamin (B12) bio-vectors. The species were fully characterized by standard analytical techniques, including X-ray crystallography for cyanocobalamin-5'-O-pyrazine and () and its N-pyrazine nitrosylated derivative (). The N-nitrosamine B12 derivatives are able to liberate low NO doses in buffer solutions and appear to be "activated" towards NO release if in contact with cultured cells. Coordination of the cis-[Re(CO)2Br4](2-) complex on the axial cyanide of B12 allows for the combined loss of CO and NO from the conjugates. The mixed CO/NO-releasing molecules show cytoprotection in an ischemia-reperfusion model but no significant enhanced synergistic effects over the relative NORMs and CORMs building constituents. PMID- 26681366 TI - Frailty Syndrome in Heart Failure Patients who are Receiving Cardiac Resynchronization. AB - BACKGROUND: We hypothesized that patients with de novo cardiac resynchronization therapy (CRT) implantation had a more intense frailty syndrome when compared to the patients who qualified for a system upgrade. METHODS: One hundred and six patients aged >=65 years were included. They were divided into two groups: de novo CRT implantation--74 patients and upgrade from standard right heart pacing- 32 patients. A CRT was finally implanted in all of the patients. Frailty was evaluated using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS). RESULTS: The average results in CSHA-CFS were statistically higher (5.3 +/- 0.8) in the de novo patients when compared to the patients who qualified for a system upgrade (4.9 +/- 0.8); P = 0.027. Frailty syndrome was recognized in 81.1% of the patients in the de novo group and in 68.7% of the patients in the upgrade group; P = 0.164. Only one patient of the 106 had no attributes of frailty (or exposed ones) syndrome. CONCLUSIONS: Frailty syndrome is a common phenomenon in patients with heart failure and over 65 years of age. The syndrome is most often recognized in patients who are de novo qualified for cardiac resynchronization. PMID- 26681367 TI - 7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII. AB - Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7 propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII. PMID- 26681368 TI - Post-traumatic stress symptoms 5 years after military deployment to Afghanistan: an observational cohort study. AB - BACKGROUND: Deployment can put soldiers at risk of developing post-traumatic stress symptoms. Despite several longitudinal studies, little is known about the timing of an increase in post-traumatic stress symptoms relative to pre deployment. Longitudinal studies starting pre-deployment, in which participants are repeatedly measured over time, are warranted to assess the timing of an increase in symptoms to ultimately assess the timing of an increase in treatment demand after deployment. METHODS: In this large observational cohort study, Dutch military personnel who were deployed to Afghanistan as part of the International Security Assistance Forces between March, 2005, and September, 2008, were assessed for post-traumatic stress symptoms with the Self-Rating Inventory for Post-traumatic Stress Disorder (SRIP) questionnaire. Participants were assessed 1 month before deployment and followed up at 1 month, 6 months, 12 months, 2 years, and 5 years after deployment, with changes in SRIP scores compared with pre deployment using a mixed model analysis. The primary outcome was the total score of post-traumatic stress symptoms measured with SRIP at pre-deployment and the five follow-up assessments, with a score of 38 used as the cutoff to indicate substantial post-traumatic stress symptoms. FINDINGS: Between March, 2005, and September, 2008, 1007 participants were recruited to this study. The results show two important effects of deployment on post-traumatic stress symptoms. A short term symptom increase within the first 6 months after deployment (symptom increase coefficient for SRIP score vs pre-deployment [beta] 0.99, 95% CI 0.50 1.48); and a long-term symptom increase at 5 years after deployment (beta 1.67, 1.14-2.20). INTERPRETATION: This study underlines the importance of long-term monitoring of the psychological health of soldiers after deployment because early detection of symptoms is essential to early treatment, which is related to improved psychological health. FUNDING: Dutch Ministry of Defense. PMID- 26681369 TI - Post-traumatic stress symptoms 5 years after military deployment to Afghanistan. PMID- 26681370 TI - The complete mitogenome of Amolops loloensis and related phylogenetic relationship among Ranidae. AB - Rufous-spotted Torrent Frog (Amolops loloensis) is a vulnerable species, which belongs to the family Ranidae and is distributed in high-gradient streams of Sichuan and Yunnan, China. In this study, we first determined the complete mitochondrial DNA sequence of A. loloensis (GenBank accession no. KT750963). The mitogenome sequence of A. loloensis was 18 926 bp in size. It contained 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and a D-loop region. Amolops loloensis shared the same gene arrangement pattern with A. mantzorum. The OL structures of A. loloensis and A. mantzorum were both located at the upstream of trnA-trnN, while the OL structures of A. ricketti and A. wuyiensis were both located at the downstream of trnA-trnN. It is of great interest to discuss the gene rearrangement mechanisms in the following study. PMID- 26681371 TI - Impact of Comprehensive Rehabilitation Therapy on Trunk Controlling Ability of Children with Cerebral Palsy. AB - Objective: This study aims to investigate the impact of comprehensive treatment on the trunk controlling ability (TCA) of children with cerebral palsy (CPC). Methods: Twenty children with spastic cerebral palsy had truncal stability parameters in the sitting posture and the symmetry parameters of left-right forward-backward centre of pressure evaluated by the stationary stability assessment module of the PK 254 P balance training instrument. After a six-month trunk control training with physical therapy technology and balancing instrument, the above indicators were re-evaluated, and the evaluations before and after the treatment were analysed to assess the therapeutic effect. Results: The difference in the truncal stability parameters before and after the treatment was statistically significant (p < 0.05); the difference in the symmetry parameters of forward-backward centre of pressure was significant (p < 0.05). Conclusions: The balancing instrument training, combined with physical therapy technology training, could effectively improve the TCA of CPC, and the balancing instrument could also provide the objective and quantitative efficacy assessment toward the TCA of CPC. PMID- 26681372 TI - Partial Protection from Metabolic Syndrome in Chronic Hepatitis C Elderly Subjects Due to Lower Triglyceride Level. AB - Background: In Taiwan, persons over 65 years old have higher prevalence of hepatitis C. Among these patients, around 50% have non-alcoholic fatty liver disease (NAFLD). Since cardiovascular diseases and diabetes are main causes of death in this age group, in this cross-sectional study, we tried to evaluate the effects of NAFLD and hepatitis C on the risk of metabolic syndrome (MetS). Methods: In total, 25 116 subjects over 65 years old who presented for routine health check-ups were enrolled. From the results of seropositivity for hepatitis C and abnormal echogenicity, they were classified into four groups: normal (N), subjects with only hepatitis C (C), subjects with only abnormal echogenicity (E) and subjects with both hepatitis C and abnormal echogenicity (CE). Results: Subjects in both groups E and CE had higher abnormal MetS components than group C. Among all five components, triglyceride (TG) was the one having the highest odds ratio (OR) in determining the incidence of MetS in groups C and E. Finally, compared to group N, both groups E and CE had significantly higher OR for having MetS. However, after adjusting for confounding factors, only the significance between groups E and N remained. In other words, higher MetS was noted in group E compared to group N and there was no difference in incidence of MetS between group CE and group N. Conclusions: Chronic hepatitis C is a protective factor against having MetS and this effect might be due to lower TG level in the elderly. Further studies are warranted for the underlying mechanisms. PMID- 26681373 TI - Sonographic Biometry of Fetal Interorbital Distance as a Predictor of Gestational Age in Enugu, Southeast Nigeria. AB - Objective: The objective of this study was to develop a sonographic technique for the measurement of fetal interorbital distance (IOD) for gestational age (GA) determination and to establish a normogram of IOD for the local population. Methods: The fronto-transverse sonographic technique was established as a feasible and reproducible technique for IOD measurement. Two independent and experienced sonographers tested the technique and had a coefficient of variation of 17.64% and 19.72%, respectively, which is statistically insignificant. The established technique was used to measure the IOD of 320 fetuses from the 13th week to 40th week GA, while standard technique was used to measure biparietal diameter (BPD), head circumference (HC) and femur length (FL) of the fetuses. The data obtained were used to determine the regression equation GA = 6.24 + 4.89 IOD for the prediction of the gestational age. Results: There was good correlation between IOD, BPD, HC and FL. The predicted normogram of IOD was compared with normogram of the Caucasian population. The result showed that there was no statistical difference between them (p < 0.05). Conclusion: Results from the study suggest that the fronto-transverse technique is a feasible and reproducible technique for IOD measurement and the established normogram of IOD can be a veritable statistic for GA prediction in our locality. PMID- 26681374 TI - Prediction of Normal Ovulation by Sonographic Folliculometry Involving Natural Cycles among Women in Ojo, Southwest Nigeria. AB - Background: Accurate prediction of ovulation is important in the management of female infertility. Aim: To determine the sonographic sensitivity of reduction in follicular size and disappearance of ovarian follicle as predictors of imminent ovulation. Methods: This was a longitudinal study involving 100 women between the ages of 18 and 35 years. Transvaginal sonography with 6.5 MHz probe frequency was performed with a General Electric (RT 2800) ultrasound machine. Dominant follicles were identified and measured in both the longitudinal and transverse planes and their disappearance was monitored prior to ovulation. Laboratory luteinizing hormone test strips were used to test serum samples collected daily from each patient to confirm the time of ovulation. Results: Pre-ovulation follicular size among the subjects was in the range of 18-36 mm while the mean follicular size was 26.78 +/- 4.03 mm. Prior to ovulation, disappearance and reduction in follicular size was noted in 59% and 41% of subjects, respectively. Luteinizing hormone test was also positive and peaked prior to ovulation in 92% of the subjects among whom follicles disappeared in 37% while their size reduced in 55%. There was no statistically significant difference between sonographic and laboratory findings (p > 0.05). Age, height, weight and body mass index do not have significant influence (p > 0.05) on follicular size and ovulation. Conclusion: Sonographic observation of complete disappearance of a dominant follicle and reduction in follicular size of surrogate follicles after follicular rupture appeared to be a reliable predictor of imminent ovulation. PMID- 26681375 TI - Current Concepts of Neurophysiological Factors in Central Regulatory Mechanism of Rapid Eye Movement Sleep: A Review. AB - Rapid eye movement (REM) sleep is physiologically different from the other phases of sleep. Most of the postulations by researchers have speculated on the role or significance of the REM sleep stage. Most of the proposed roles that are attributed to REM sleep in vital brain functions are still mere speculations. For example, there is no clear evidence to suggest that REM sleep may play a particular role or may mediate a proposed mechanism for a specific brain function. The aim of this review is to identify those vital processes in brain function believed to be REM sleep driven, and which have featured prominently in the works of researchers in the past. The method adopted in this review was that of information gathering from sources which included published works of past and present researchers, articles on sleep presented in seminars and conferences, published articles on sleep, lecture notes on sleep physiology, textbooks of current editions in neuroscience, reports and published works accessed from the Internet using search engines such as Google, Mamma, PubMed etc. The postulations and hypothesized roles of REM sleep in vital brain function have been clearly highlighted in this review. It is concluded from this review that neural factors involved in the central mechanisms of REM sleep are not fully understood. Nevertheless, information noted in this review lends further credence to the notion that REM sleep is crucial and probably the most important sleep phase. It is hoped that facts in the proposals and postulations chronicled in this review will serve as important information source for neuroscientists and different researchers engaged in the subject of sleep. PMID- 26681377 TI - Cloning and Constructing a Plasmid Encoding Leishmania Eukaryotic Initiation Factor Gene of Leishmania major Fused with Green Fluorescent Protein Gene as a Vaccine Candidate. AB - Objective: Leishmaniasis is usually treated with chemotherapy; however, toxicity, resistance and high-cost limit use of the chemical drugs. Leishmania eukaryotic initiation factor (LeIF) protein acts the same as interleukin (IL)-12 and reduces the secretion of IL-4 in lymph node cells of mice infected with Leishmania major. The aim of this study was cloning of the gene encoding LeIF antigen into eukaryotic expression plasmid pEGFP-N1. Methods: DNA was extracted from Iranian strain of the L major (MRHO/IR/75/ER) promastigotes. The full-length sequence of LeIF was amplified with Pfu DNA polymerase using a specific primer. The amplified LeIF was cloned into a pJET1.2/blunt vector. Then this fragment was digested with HindIII and EcoRI and was subcloned into the pEGFP-N1 vector. Confirmation of the cloning was done by colony polymerase chain reaction (PCR). Results: Leishmania eukaryotic initiation factor gene was successfully cloned and subcloned into pJET1.2 and pEGFP-N1 plasmids, respectively. The results of colony PCR, restriction analysis and sequencing confirmed them. Conclusions: We cloned LeIF gene which could be expressed in eukaryotic cells in vivo and could be used as a vaccine candidate against leishmaniasis in future studies. PMID- 26681379 TI - Traumatic Dorsal Dislocation of the Four Ulnar Metacarpals. AB - The swollen, painful hand is a familiar sight in the emergency department (ED), and often is seen in the context of alcohol intake, following a fight or in association with multiple trauma, all of which can make accurate assessment challenging. We report a case of complete dorsal dislocation of the four ulnar metacarpals and highlight the importance of early diagnosis and treatment for this unusual injury. PMID- 26681381 TI - [Mild therapeutic hypothermia in cardiogenic shock : Retrospective analysis of 80 patients with preclinical cardiac arrest due to cardiac causes]. AB - BACKGROUND: The mortality in patients with cardiogenic shock after out-of hospital cardiac arrest (OHCA) remains high despite advances in resuscitation and early revascularization strategies. The use of mild therapeutic hypothermia (MTH) for improvement of survival and neurological outcome in patients with cardiogenic shock is currently subject to renewed discussion. OBJECTIVE: The aim of this study was the detection of risk factors for mortality and morbidity in patients under MTH in cardiogenic shock following preclinical resuscitation for OHCA. METHODS: A total of 80 consecutive patients in cardiogenic shock after successful resuscitation (mean age 60 +/- 3.2 years) treated with MTH were retrospectively analyzed. Patients were cooled to 33 degrees C for 24 h using an endovascular cooling device. Neurological outcome was assessed after 2 months based on the Glasgow-Pittsburgh cerebral performance category (CPC) and correlated with various blood parameter values. RESULTS: After 2 months 31 patients (39 %) showed a good neurological recovery with CPC scores of 1-2, 20 patients (25 %) had a poor neurological outcome with CPC scores of 3-4 and 29 (36 %) patients enrolled in the trial died (CPC 5). Patients with a poor outcome showed significantly higher mean serum levels for lactate, creatinine and urea. In addition, these patients showed a continuous increase of serum neuron-specific enolase (NSE) values in contrast to patients with a good outcome (? NSE from admission to day 1, CPC 1 and 2: - 10.6 +/- 3 ug/l and CPC 3-5: 33 +/- 12 ug/l, p = 0.02). CONCLUSION: Changes in the course of serum creatinine, urea and NSE levels within the first 72 h after OHCA could provide valuable additional information for the early assessment of the neurological prognosis in patients treated with MTH. PMID- 26681382 TI - Influence of the serum levels of immunoglobulins on clinical outcomes in medical intensive-care patients. AB - INTRODUCTION: Endogenous immunoglobulins (Igs) are of fundamental importance in the host defense after microbial infections. However, the therapeutic administration of intravenous IgG (IVIgG) has not yet been shown to improve clinical outcomes in patients suffering from sepsis, and in the case of IgM containing preparations (IVIgGMA) the positive evidence is only weak. Recently published studies implicate that Ig levels on admission could have an impact on the patient's response to IVIg treatment and on outcomes of critically ill patients. METHODS: In this noninterventional study, the serum levels of IgG, IgM, and IgA were determined in 340 medical patients on ICU admission, and clinical outcomes were prospectively recorded (ICU mortality, need for renal replacement therapy (RRT), need for mechanical ventilation, substitution of coagulation factors, and amount of red cell transfusions). Patients were prospectively grouped according to their main reason for ICU admission (sepsis, respiratory failure, cardiovascular diseases, acute renal failure, postoperative condition, state after cardiopulmonal resuscitation, gastrointestinal diseases, and others). RESULTS AND DISCUSSION: There was no correlation between the Ig levels on admission and ICU mortality neither in the total cohort of medical ICU patients nor in any prespecified subgroup. However, in a logistic regression model that was adjusted for APACHE II score on admission, an increase in serum IgG was associated with a reduced need for mechanical ventilation in patients suffering from cardiovascular disease. On the other hand, in patients suffering from sepsis, an increased level of IgM was linked to an increased administration of coagulation factors. CONCLUSION: Our data do not support the hypothesis that serum levels of immunoglobulins are linked to mortality in medical ICU patients. PMID- 26681383 TI - Stoma placement in obstructive rectal cancer prior to neo-adjuvant treatment and definitive surgery: A practical guideline. AB - INTRODUCTION: Mechanical bowel obstruction in rectal cancer is a common problem, requiring stoma placement to decompress the colon and permit neo-adjuvant treatment. The majority of patients operated on in our hospital are referred; after stoma placement at the referring centre without overseeing final type of surgery. Stoma malpositioning and its effects on rectal cancer care are described. METHODS: All patients who underwent surgery for locally advanced or locally recurrent rectal cancer between 2000 and 2013 in our tertiary referral centre were reviewed and included if they received a stoma before curative surgery. Patients with recurrent rectal cancer were only included if the stomas from the primary surgery had been restored. The main outcome measures are stoma malpositioning, postoperative and stoma-related complications. RESULTS: A total of 726 patients were included; of these, 156 patients (21%) had a stoma before curative surgery. In the majority of patients, acute or pending large bowel obstruction was the main indication for emergent stoma creation; some of the patients had tumour-related fistulae. In 53 patients (34%), the stoma required revision during definitive surgery. No significant differences were found regarding postoperative complications. CONCLUSION: One-third of the previously placed emergency stomas were considered to be located inappropriately and required revision. We were able to avoid increased complication rates in patients with a malpositioned stoma, however unnecessary surgery for an inappropriately placed stoma should be avoided to decrease patient inconvenience and risks. An algorithm is proposed for the placement of a suitable stoma. PMID- 26681384 TI - Palliative care case conferences in long-term care: views of family members. AB - AIMS AND OBJECTIVES: This paper examines the use of structured Palliative Care Case Conferences in long-term care. The issues families bring to the Palliative Care Case Conference, their level of distress prior to the conference, the extent to which these issues are addressed by staff and family satisfaction with this process are described. BACKGROUND: In most developed countries, up to 30% of older people die in long-term care. A palliative approach generally refers to the resident and family as the 'unit of care'. Interventions, which include family in palliative care, are required in this setting. DESIGN: Descriptive and thematic results from the intervention arm of a pre-post, sequential mixed method study. METHODS: Examination of documents of 32 resident/family dyads participating in a Palliative Care Case Conference, and interviews with the residents' family postintervention. RESULTS: Main concerns raised by family members prior to a Palliative Care Case Conference were physical and medical needs, pain, end-of life care planning and nutrition and hydration. Families rated a high level of concern, 7.5 on a 10-point rating scale, prior to the Palliative Care Case Conference. A formalised Palliative Care Case Conference process ensured issues relating to end-of-life care planning, pastoral care, pain and comfort and physical and medical needs were well documented by staff. Issues relating to care processes and the family role in care were less well documented. All families, interviewed postintervention, recommended Palliative Care Case Conferences; and over 90% of families felt their issues were addressed to their satisfaction. Families also reported an increased understanding of the resident's current and future care. CONCLUSIONS: The Palliative Care Case Conference in long-term care provides an important platform for family to voice concerns. Palliative Care Case Conference documentation indicates that staff are attending to these issues, although more reference to concerns relating to care processes and the family role could be made. IMPLICATIONS FOR PRACTICE: Increased communication between staff and family, in the form of a Palliative Care Case Conference, may reduce stress, anxiety and unwanted hospitalisations during the palliative phase. PMID- 26681385 TI - Nicotine and Cotinine Levels With Electronic Cigarette: A Review. AB - BACKGROUND: Since their introduction in 2004, electronic cigarettes (e cigarettes) have gained popularity worldwide. E-cigarettes are marketed as nicotine delivery devices. Commonly reported reasons for use include to quit smoking, to reduce urge to smoke, or the perceived lower risk alternative to smoking. But what are the actual amounts of nicotine delivered? AIM: This review summarizes all the published studies concerning nicotine or cotinine levels following e-cigarette use. METHODS: A literature search was conducted from the PubMed database, from 1985 to January 2014, using the following terms: electronic cigarette(s), e-cigarette(s), electronic nicotine delivery system, cotinine, and nicotine. Articles were excluded if they were not pertinent according to our criteria. References of all relevant articles were also evaluated. RESULTS: Eight studies were included in this review. The following information was extracted from the articles: population size, age of participants, recruitment, inclusion and exclusion criteria, concentration of nicotine in refills liquids, study sample design, and observed concentrations. Following design of studies, plasma nicotine Cmax was observed between 0 and 5 ng/mL (no significant changes) or between 13.9 and 16.3 ng/mL (similar to a tobacco cigarette) with a Tmax between 70 and 75 minutes. Cotinine levels after "vaping" an e-cigarette are similar to a tobacco cigarette. CONCLUSION: This review summarizes e-cigarette studies that contain information on nicotine or cotinine levels. The peak concentration of nicotine appears to be dependent on the use and dose level of e-cigarette cartridge. The value of this peak concentration is similar to the value found with a tobacco cigarette. However, the time corresponding to the peak concentration is delayed compared to a tobacco cigarette. PMID- 26681386 TI - Are cardiovascular and metabolic responses to field walking tests interchangeable and obesity-dependent? AB - PURPOSE: To investigate if cardiovascular and metabolic responses to the six minute walk test (6MWT) and incremental shuttle walking test (ISWT) are in agreement with cardiopulmonary exercise testing (CPX) and determine if both submaximal tests are interchangeable in obese and eutrophic individuals. METHOD: Observational and cross-sectional study included 51 obese women (ObG) and 21 controls (CG) (20-45 years old). Subjects underwent clinical evaluation, CPX, the 6MWT and ISWT. We applied Bland-Altman plots to assess agreement between walking tests and CPX. Correlation analysis assessed relationships between key variables. RESULTS: There was an agreement between CPX and both the 6MWT [oxygen uptake (VO2 mL kg(-1) min(-1)) = 6.9 (CI: 5.7-8.1), and heart rate (bpm) = 37.0 (CI: 33.3 40.7)] and ISWT [VO2 (mL kg(-1) min(-1)) = 6.1 (CI: 4.9-7.3), and heart rate (bpm) = 36.2 (CI: 32.1-40.3)]. We found similar cardiovascular and metabolic responses to both tests in the ObG but not in the CG. Strong correlations were demonstrated between 6MWT and ISWT variables: VO2 ( r = 0.70); dyspnoea (r = 0.80); and leg fatigue (r = 0.70). CONCLUSIONS: 6MWT and ISWT may both hold interchangeable clinical value when contrasted with CPX in obese women and may be a viable alternative in the clinical setting when resources and staffing are limited. Implications for Rehabilitation Obesity is a worldwide epidemic, with high prevalence in women, and it is associated to impaired cardiorespiratory fitness and functional capacity as well as high mortality risk. Assessing oxygen uptake by means of cardiopulmonary exercise testing is the gold standard method for evaluating and stratifying cardiorespiratory fitness, however it is not ever applied due to costs and staffing. Walking field tests may be a cost-effective approach that provides valuable information regarding the functional capacity in agreement to metabolic and cardiovascular responses of cardiopulmonary exercise testing. PMID- 26681387 TI - Quantitative serology assays for determination of antibody responses to Ebola virus glycoprotein and matrix protein in nonhuman primates and humans. AB - The West Africa Ebola virus disease (EVD) outbreak has reached unprecedented magnitude and caused worldwide concerns for the spread of this deadly virus. Recent findings in nonhuman primates (NHPs) demonstrate that antibodies can be protective against EVD. However, the role of antibody response in vaccine mediated protection is not fully understood. To address these questions quantitative serology assays are needed for measurement of the antibody response to key Ebola virus (EBOV) proteins. Serology enzyme-linked immunosorbent assays (ELISA's), using a reference detection antibody, were developed in order to standardize the quantitation of antibody levels in vaccinated NHPs or in humans exposed to EBOV or immunized with an EBOV vaccine. Critical reagents were generated to support the development of the serology ELISAs. Recombinant EBOV matrix protein (VP40) was expressed in Escherichia coli and purified. Two variants of the glycoprotein (GP), the ectodomain lacking the transmembrane domain (GPDeltaTM), and an engineered GP lacking the mucin-like domain (GPDeltamuc) were expressed and purified from mammalian cell systems. Using these proteins, three ELISA methods were developed and optimized for reproducibility and robustness, including stability testing of critical reagents. The assay was used to determine the antibody response against VP40, GPDeltaTM, and GPDeltamuc in a NHP vaccine study using EBOV virus-like particles (VLP) vaccine expressing GP, VP40 and the nucleoprotein. Additionally, these ELISAs were used to successfully detect antibody responses to VP40, GPDeltaTM and GPDeltamuc in human sera from EBOV infected individuals. PMID- 26681388 TI - Clinical Use of 3D Printing Guide Plate in Posterior Lumbar Pedicle Screw Fixation. AB - BACKGROUND This study aimed to evaluate the clinical efficacy of use of a 3D printing guide plate in posterior lumbar pedicle screw fixation. MATERIAL AND METHODS We enrolled 43 patients receiving posterior lumbar pedicle screw fixation. The experimental group underwent 3D printing guide plate-assisted posterior lumbar pedicle screw fixation, while the control group underwent traditional x-ray-assisted posterior lumbar pedicle screw fixation. After surgery, CT scanning was done to evaluate the accuracy of screw placement according to the Richter standard. RESULTS All patients were followed up for 1 month. The mean time of placement for each screw and the amount of hemorrhage was 4.9+/-2.1 min and 8.0+/-11.1 mL in the experimental group while 6.5+/-2.2 min and 59.9+/-13.0 mL in the control group, respectively, with significant differences (p<0.05). The fluoroscopy times of each screw placement was 0.5+/-0.4 in the experimental group, which was significantly lower than that in the control group 1.2+/-0.7 (p<0.05). The excellent and good screw placement rate was 100% in the experimental group and 98.4% in the control group, without any statistical difference (P>0.05). No obvious complications were reported in either group. CONCLUSIONS Compared with the traditional treatment methods, the intra-operative application of 3D printing guide plate can shorten the operation time and reduce the amount of hemorrhage. It can also reduce the fluoroscopy times compared with the traditional fluoroscopy, which cannot improve the accuracy rate of screw placement. PMID- 26681389 TI - The Relationship Between Reticular Pseudodrusen and Severity of AMD. PMID- 26681390 TI - Risk Factors and Incidence of Macular Edema after Cataract Surgery: A Database Study of 81984 Eyes. AB - PURPOSE: To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. DESIGN: Retrospective database study of electronic medical records (EMRs). PARTICIPANTS: A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites. METHODS: Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded. MAIN OUTCOME MEASURE: Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery. RESULTS: Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57-4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45-9.07), uveitis (RR, 2.88; 95% CI, 1.50-5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56-5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60-5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36 2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12-7.58) and rose proportionately with increasing severity of DR. CONCLUSIONS: Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs. PMID- 26681391 TI - Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study. AB - PURPOSE: To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large sample. DESIGN: Community-based cohort study in Melbourne, Victoria, Australia. PARTICIPANTS: A total of 21,130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007. METHODS: Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet. MAIN OUTCOME MEASURES: Detection of RPD based on color fundus photographs. RESULTS: Prevalence of RPD was 0.41% (87 of 21,130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 MUm; 76+/-4 vs. 68+/-9 years; P < 0.001). Increasing age, female gender, being a current smoker, as well as focal pigmentary abnormalities and large drusen (>125 MUm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153; 95% confidence interval [CI], 53-442), followed by choroidal neovascularization (CNV; OR, 90; 95% CI, 26 310), intermediate AMD (OR, 33; 95% CI, 14-77), and early AMD (OR, 12; 95% CI, 5 31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P < 0.05). CONCLUSIONS: Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen. PMID- 26681393 TI - Evaluation of Screening for Retinopathy of Prematurity by ROPtool or a Lay Reader. AB - PURPOSE: To determine if (1) tortuosity assessment by a computer program (ROPtool, developed at the University of North Carolina, Chapel Hill, and Duke University, and licensed by FocusROP) that traces retinal blood vessels and (2) assessment by a lay reader are comparable with assessment by a panel of 3 retinopathy of prematurity (ROP) experts for remote clinical grading of vascular abnormalities such as plus disease. DESIGN: Validity and reliability analysis of diagnostic tools. PARTICIPANTS: Three hundred thirty-five fundus images of prematurely born infants. METHODS: Three hundred thirty-five fundus images of prematurely born infants were obtained by neonatal intensive care unit nurses. A panel of 3 ROP experts graded 84 images showing vascular dilatation, tortuosity, or both and 251 images showing no evidence of vascular abnormalities. These images were sent electronically to an experienced lay reader who independently graded them for vascular abnormalities. The images also were analyzed using the ROPtool, which assigns a numerical value to the level of vascular abnormality and tortuosity present in each of 4 quadrants or sectors. The ROPtool measurements of vascular abnormalities were graded and compared with expert panel grades with a receiver operating characteristic (ROC) curve. Grades between human readers were cross-tabulated. The area under the ROC curve was calculated for the ROPtool, and sensitivity and specificity were computed for the lay reader. MAIN OUTCOME MEASURES: Measurements of vascular abnormalities by ROPtool and grading of vascular abnormalities by 3 ROP experts and 1 experienced lay reader. RESULTS: The ROC curve for ROPtool's tortuosity assessment had an area under the ROC curve of 0.917. Using a threshold value of 4.97 for the second most tortuous quadrant, ROPtool's sensitivity was 91% and its specificity was 82%. Lay reader sensitivity and specificity were 99% and 73%, respectively, and had high reliability (kappa, 0.87) in repeated measurements. CONCLUSIONS: ROPtool had very good accuracy for detection of vascular abnormalities suggestive of plus disease when compared with expert physician graders. The lay reader's results showed excellent sensitivity and good specificity when compared with those of the expert graders. These options for remote reading of images to detect vascular abnormalities deserve consideration in the quest to use telemedicine with remote reading for efficient delivery of high-quality care and to detect infants requiring bedside examination. PMID- 26681394 TI - Joint Management of Cataract Surgery by Ophthalmologists and Optometrists. AB - PURPOSE: To estimate the rate and geographic variation of cataract surgery that is managed jointly by ophthalmologists and optometrists in aging Americans. DESIGN: Database study. PARTICIPANTS: United States fee-for-service (FFS) Medicare Part B beneficiaries and their providers. METHODS: Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare and Medicaid were used to identify cataract surgery claims among FFS Medicare Part B beneficiaries in all 50 states and the District of Columbia in 2012 and 2013. Payments and joint management rates of cataract surgery by ophthalmologists and optometrists were calculated for each United States state. Geographic variations were evaluated by using the extremal quotient and coefficient of variation (CV). MAIN OUTCOME MEASURES: Medicare allowed payments for cataract surgery (Current Procedural Terminology codes 66982 and 66984) and number of unique FFS Medicare Part B beneficiaries undergoing cataract surgery. RESULTS: The overall national rate of joint management of cataract surgery by ophthalmologists and optometrists among FFS Medicare Part B beneficiaries was 10.9% (range by state, 0%-75%) in 2012 and 11.1% (range by state, 0%-63%) in 2013. In 2013, the mean extremal quotient was 67 and the CV was 82.2, demonstrating very high variation in joint management between states. The Medicare allowed payment to optometrists in the joint management of cataract surgery was 2.1% of the total Medicare allowed payments for cataract surgery codes in 2012 and 2013. Twenty percent and 24% of all Medicare-participating optometrists submitted 10 or more Medicare claims in the joint management of cataract surgery in 2012 and 2013, respectively. CONCLUSIONS: The overall rate of joint management of cataract surgery by ophthalmologists and optometrists among Medicare beneficiaries was 10.9% in 2012 and 11.1% in 2013. Very high geographic variation was documented, with joint management rates ranging from 0% to 63% across states in 2013. PMID- 26681395 TI - Cell autonomous roles of Nedd4 in craniofacial bone formation. AB - Nedd4 is an E3 ubiquitin ligase that has an essential role in craniofacial development. However, how and when Nedd4 controls skull formation is ill defined. Here we have used a collection of complementary genetic mouse models to dissect the cell-autonomous roles of Nedd4 in the formation of neural crest cell derived cranial bone. Removal of Nedd4 specifically from neural crest cells leads to profound craniofacial defects with marked reduction of cranial bone that was preceded by hypoplasia of bone forming osteoblasts. Removal of Nedd4 after differentiation of neural crest cells into progenitors of chondrocytes and osteoblasts also led to profound deficiency of craniofacial bone in the absence of cartilage defects. Notably, these skull malformations were conserved when Nedd4 was specifically removed from the osteoblast lineage after specification of osteoblast precursors from mesenchymal skeletal progenitors. We further show that absence of Nedd4 in pre-osteoblasts results in decreased cell proliferation and altered osteogenic differentiation. Taken together our data demonstrate a novel cell-autonomous role for Nedd4 in promoting expansion of the osteoblast progenitor pool to control craniofacial development. Nedd4 mutant mice therefore represent a unique mouse model of craniofacial anomalies that provide an ideal resource to explore the cell-intrinsic mechanisms of neural crest cells in craniofacial morphogenesis. PMID- 26681396 TI - Quality evaluation of the leaves of Magnolia officinalis var. biloba using high performance liquid chromatography fingerprint analysis of phenolic compounds. AB - The high-performance liquid chromatography fingerprint method is a simple and reliable technique to evaluate the quality of leaves of Magnolia officinalis Rehd.et Wils. var. biloba Rehd.et Wils. We used the following bioactive phenolic constituents as reference compounds: rutin, afzelin, hyperoside, isoquercitrin, quercetin-3-O-alpha-l-rhamnoside, honokiol and magnolol. The conditions of an Agilent 1200 HPLC were: YMC-Pack-ODS-AQ column (250 * 4.6 mm id S-5 MUm, 12 nm), mobile phase acetonitrile and 0.2% phosphoric acid in a gradient elute mode, flow rate 1.0 mL/min, detection wavelength 280 nm and column temperature 30 degrees C. The analytical method was validated in terms of linearity, stability, repeatability, precision and recovery tests. While performing fingerprint analysis, we identified 11 peaks as characteristic peaks and assessed the similarities of 17 samples collected from different geological regions of China. The peak areas were used to evaluate the variation in the chemical composition of the tested samples. For this purpose, we performed hierarchical cluster analysis of the peak areas. Our results indicate that simultaneous determination of multiple ingredients could be done through chromatographic fingerprint analysis. Therefore, this high-performance liquid chromatography fingerprint method was readily utilized to evaluate the quality of leaves of M. officinalis var.biloba, which are used in several traditional herbal preparations. PMID- 26681398 TI - Atrial Fibrillation as a Prognostic Indicator in Medium to Large-Sized Dogs with Myxomatous Mitral Valvular Degeneration and Congestive Heart Failure. AB - BACKGROUND: The prevalence and prognostic importance of atrial fibrillation (AF) on survival in nonsmall breed dogs with myxomatous mitral valvular disease (MMVD) and congestive heart failure (CHF) remain unknown. AIM: To identify the prevalence of AF in nonsmall breed dogs with CHF because of MMVD and to characterize the impact of AF on survival outcome. ANIMAL: Sixty-four client owned dogs (>15 kg) with MMVD and CHF. METHODS: Retrospective review of medical records for dogs weighing >15 kg with MMVD treated for CHF. RESULTS: Thirty-three dogs presented with AF or developed AF during follow-up examinations, and 31 dogs were free of AF until cardiac-related death. For dogs with AF, median survival time (MST) was 142 days (range: 9-478) while dogs without AF lived 234 days (range: 13-879 days). AF increased risk of cardiac-related death (HR = 2.544; 95% CI = 1.41-4.59; P = .0019) when compared to dogs without AF. MST was significantly prolonged for dogs with AF whose rates were adequately controlled (<160 bpm; 171 days; n = 13) when compared to dogs that failed to respond to negative chronotropic agents (61 days; n = 20; P = .032). The administration of combination treatment (diltiazem and digoxin) significantly decreased median HR to 144 bpm (range: 84-218 bpm) in dogs with AF and significantly prolonged MST (diltiazem+digoxin: 130 days versus diltiazem: 35 days, P = .0241) when compared to diltiazem alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Inadequately controlled AF is associated with a higher rate of mortality. Optimization of therapeutic strategies for the rate control of AF remains determined. PMID- 26681397 TI - An integrated bioinformatics analysis to dissect kinase dependency in triple negative breast cancer. AB - BACKGROUND: Triple-Negative Breast Cancer (TNBC) is an aggressive disease with a poor prognosis. Clinically, TNBC patients have limited treatment options besides chemotherapy. The goal of this study was to determine the kinase dependency in TNBC cell lines and to predict compounds that could inhibit these kinases using integrative bioinformatics analysis. RESULTS: We integrated publicly available gene expression data, high-throughput pharmacological profiling data, and quantitative in vitro kinase binding data to determine the kinase dependency in 12 TNBC cell lines. We employed Kinase Addiction Ranker (KAR), a novel bioinformatics approach, which integrated these data sources to dissect kinase dependency in TNBC cell lines. We then used the kinase dependency predicted by KAR for each TNBC cell line to query K-Map for compounds targeting these kinases. We validated our predictions using published and new experimental data. CONCLUSIONS: In summary, we implemented an integrative bioinformatics analysis that determines kinase dependency in TNBC. Our analysis revealed candidate kinases as potential targets in TNBC for further pharmacological and biological studies. PMID- 26681399 TI - "Intercellular bridges" in a case of well differentiated squamous carcinoma. AB - Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node. PMID- 26681400 TI - Optimization of anti-TNF therapy in patients with Inflammatory Bowel Disease. AB - After the introduction of anti-tumor necrosis factor (anti-TNF) agents, the clinical outcome of patients with Inflammatory Bowel Disease (IBD) has improved significantly. However, use of anti-TNF therapy is complicated by loss of response. In order to maintain remission, adequate serum levels are required. Hence, therapeutic drug monitoring (TDM) is important in order to optimize serum drug levels, especially in patients with loss of response to these agents. Optimization of anti-TNF therapy by applying TDM enables clinicians to regain response to TNF blockers in a significant proportion of patients. It is important to use anti-TNF agents in their most optimal way, since these therapeutic agents are expensive and the medical options after failing anti-TNF therapy are limited. Here, we will discuss how to optimize treatment with anti-TNF agents in IBD patients in order to improve treatment efficacy, prevent anti-drug antibody formation, reduce side effects, discontinue unnecessary treatment and manage costs. PMID- 26681401 TI - Ultrasonic-electrodeposition of PtPd alloy nanoparticles on ionic liquid functionalized graphene paper: towards a flexible and versatile nanohybrid electrode. AB - Here we fabricate a new type of flexible and versatile nanohybrid paper electrode by ultrasonic-electrodeposition of PtPd alloy nanoparticles on freestanding ionic liquid (IL)-functionalized graphene paper, and explore its multifunctional applications in electrochemical catalysis and sensing systems. The graphene-based paper materials demonstrate intrinsic flexibility, exceptional mechanical strength and high electrical conductivity, and therefore can serve as an ideal freestanding flexible electrode for electrochemical devices. Furthermore, the functionalization of graphene with IL (i.e., 1-butyl-3-methylimidazolium tetrafluoroborate) not only increases the electroactive surface area of a graphene-based nanohybrid paper electrode, but also improves the adhesion and dispersion of metal nanoparticles on the paper surface. These unique attributes, combined with the merits of an ultrasonic-electrodeposition method, lead to the formation of PtPd alloy nanoparticles on IL-graphene paper with high loading, uniform distribution, controlled morphology and favourable size. Consequently, the resultant nanohybrid paper electrode exhibits remarkable catalytic activity as well as excellent cycle stability and improved anti-poisoning ability towards electrooxidation of fuel molecules such as methanol and ethanol. Furthermore, for nonenzymatic electrochemical sensing of some specific biomarkers such as glucose and reactive oxygen species, the nanohybrid paper electrode shows high selectivity, sensitivity and biocompatibility in these bio-catalytic processes, and can be used for real-time tracking hydrogen peroxide secretion by living human cells. All these features demonstrate its promising application as a versatile nanohybrid electrode material in flexible and lightweight electrochemical energy conversion and biosensing systems such as bendable on-chip power sources, wearable/implantable detectors and in vivo micro-biosensors. PMID- 26681402 TI - Miltenberger blood group typing by real-time polymerase chain reaction (qPCR) melting curve analysis in Thai population. AB - OBJECTIVES: To develop reliable and convenient methods for Miltenberger (Mi(a) ) blood group typing. AIM: To apply real-time polymerase chain reaction (qPCR) melting curve analysis to Mi(a) blood group typing. BACKGROUND: The Mi(a) blood group is the collective set of glycophorin hybrids in the MNS blood group system. Mi(a+) blood is common among East Asians and is also found in the Thai population. Incompatible Mi(a) blood transfusions pose the risk of life threatening haemolysis; therefore, Mi(a) blood group typing is necessary in ethnicities where the Mi(a) blood group is prevalent. METHODS/MATERIALS: One hundred and forty-three blood samples from Thai blood donors were used in the study. The samples included 50 Mi(a+) samples and 93 Mi(a-) samples, which were defined by serology. The samples were typed by Mi(a) typing qPCR, and 50 Mi(a+) samples were sequenced to identify the Mi(a) subtypes. Mi(a) subtyping qPCR was performed to define GP.Mur. Both Mi(a) typing and Mi(a) subtyping were tested on a conventional PCR platform. RESULTS: The results of Mi(a) typing qPCR were all concordant with serology. Sequencing of the 50 Mi(a+) samples revealed 47 GP.Mur samples and 3 GP.Hop or Bun samples. Mi(a) subtyping qPCR was the supplementary test used to further define GP.Mur from other Mi(a) subtypes. Both Mi(a) typing and Mi(a) subtyping performed well using a conventional PCR platform. CONCLUSION: Mi(a) typing qPCR correctly identified Mi(a) blood groups in a Thai population with the feasibility of Mi(a) subtype discrimination, and Mi(a) subtyping qPCR was able to further define GP.Mur from other Mi(a) subtypes. PMID- 26681403 TI - The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial. AB - Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke-induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke-induced vascular injury. 32 male rats and a double-blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule-1 (CD31), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2 related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO-1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase-1 (HO-1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM-1, VCAM-1 and ET-1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO-1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke-induced vascular injury. PMID- 26681404 TI - Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors. AB - Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency. PMID- 26681406 TI - Cardiorespiratory fitness in 16 025 adults aged 18-91 years and associations with physical activity and sitting time. AB - Our aim was to provide up-to-date cardiorespiratory fitness reference data for adults of all ages and to investigate associations between cardiores-piratory fitness and leisure time physical activity as well as sitting time. In the Danish Health Examination Survey 2007-2008, cardiorespiratory fitness was estimated in 16 025 individuals aged 18-91 years from validated cycle ergometer exercise tests. Level of leisure time physical activity (sedentary, light, moderate, and vigorous) and daily sitting time in hours was obtained from a self-administered questionnaire. Men had 20-33% higher cardiorespiratory fitness than women, depending on age, and cardiorespiratory fitness decreased by 0.26 and 0.23 mL/min/kg per year in men and women, respectively. Cardiorespiratory fitness was higher among participants who reported a high level of physical activity in leisure time compared with participants who were sedentary. Among sedentary or lightly physically active participants, inverse associations between total daily sitting time and cardiorespiratory fitness were found, while there was no association between sitting time and cardiorespiratory fitness among moderately or vigorously physically active participants. These data on cardiorespiratory fitness can serve as useful reference material. Although reluctant to conclude on causality, sitting time might impact cardiorespiratory fitness among individuals with low levels of leisure time physical activity. PMID- 26681405 TI - Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration. AB - Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration. PMID- 26681407 TI - One-Day Use of Preoperative Topical Nonsteroidal Anti-Inflammatory Drug Prevents Intraoperative Prostaglandin Level Elevation During Femtosecond Laser-Assisted Cataract Surgery. AB - PURPOSE: To determine if pretreatment with topical nonsteroidal anti-inflammatory drug (NSAID) prior to femtosecond laser-assisted cataract surgery (FLACS) prevents intraoperative prostaglandin level elevation as a potential risk factor of postoperative complications. PATIENTS AND METHODS: Thirty-six patients with clinically significant cataract and without any concomitant general or ophthalmic disease were enrolled into the three age-matched groups of the study. The mean age of the patients was 62.3 +/- 13.1 years. The first group of patients underwent traditional phacoemulsification (Control group), on the second group of patients FLACS was performed, and the third group of patients received topical 0.1% nepafenac pretreatment for 1one day prior to FLACS. Before the phacoemulsification part of the cataract surgery, approximately 110 uL of aqueous humor was collected in all groups. Total prostaglandin concentrations of the collected aqueous humor samples were evaluated by enzyme immunoassay (EIA). RESULTS: The mean of the total prostaglandin concentrations of the aqueous humor samples was 208.8 +/- 140.5 pg/mL in patients in the control group, 1449.1 +/- 1019.7 pg/mL in the FLACS group (p > 0.001), and 92.2 +/- 51.7 pg/mL in the group pretreated with topical NSAID before the FLACS (p > 0.001 compared to FLACS; p > 0.01 compared to control), respectively. CONCLUSIONS: FLACS surgery increases intracameral prostaglandin concentration. However, using preoperative 1-day-long nonsteroid anti-inflammatory drops prior to FLACS, this intraoperative increase diminishes. Our study raises the possibility that NSAID pretreatment may be routinely administered before FLACS cataract surgeries to achieve a further decrease in the potential complications of increased total prostaglandin concentration during FLACS surgeries. PMID- 26681408 TI - Impact of carbon nanotubes on the toxicity of inorganic arsenic [AS(III) and AS(V)] to Daphnia magna: The role of certain arsenic species. AB - As a type of emerging nanomaterial, hydroxylated multiwalled carbon nanotubes (OH MWCNTs) may interact with other pollutants in the aquatic environments and further influence their toxicity, transport, and fate. Thus, evaluation of toxicity to arsenic in the presence of CNTs needs to receive much more attention. The present study was conducted to explore the underlying mechanisms of OH-MWCNT induced arsenic (As[III] and As[V]) toxicity changes in the aquatic organism Daphnia magna at different pH levels. The most toxic species for As(III) and As(V) to D. magna were found to be H2 AsO3 (-) and H2 AsO4 (-) . It appeared that the pH values were of greatest importance when the biological toxicity of As(III) and As(V) was compared. Furthermore, the effects of OH-MWCNTs on arsenic toxicity to D. magna indicated that the presence of OH-MWCNTs could enhance the toxicity of arsenic. The interactions of arsenic with OH-MWCNTs were further investigated by conducting adsorption experiments. The adsorption capacity of As(V) by OH MWCNTs was found to be higher than that of As(III). To conclude, adsorption of certain arsenic species onto OH-MWCNTs is crucial for a reliable interpretation of enhanced toxicity. Environ Toxicol Chem 2016;35:1852-1859. (c) 2016 SETAC. PMID- 26681409 TI - Impact of Symptoms on Daily Life in People at Risk of Rheumatoid Arthritis. PMID- 26681411 TI - Person-Centered Dementia Care and Sleep in Assisted Living Residents With Dementia: A Pilot Study. AB - The sleep of people with dementia living in long-term care is known to be disturbed. This pre-post controlled pilot study examined the effects of a person centered dementia care intervention on sleep in assisted living residents with dementia. The three-month intervention included in-class staff training plus supervision and support in practice. The sleep-wake patterns were measured using actigraphy for three consecutive days at baseline and postintervention. Sixteen residents from the intervention and six from the control groups completed the study. The intervention group had significantly more nighttime sleep at posttest. After adjusting for baseline, the intervention group exhibited significantly less daytime sleep and more nighttime sleep. Person-centered dementia care may be effective for improving sleep of residents with dementia. PMID- 26681425 TI - Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis. AB - Metformin (Met) and coenzyme Q10 (CoQ10) are reported to have therapeutic functions in several inflammatory diseases. These drugs have shown anti inflammatory effects and have been utilized in mouse models of rheumatoid arthritis (RA). However, there is no evidence of the additive effect of Met and CoQ10 in RA. Although Met and CoQ10 may be involved in the improvement of mitochondrial dysfunction, limited information is available regarding whether this effect can improve mitochondrial dysfunction in RA in particular. In this study, we sought to determine whether Met and CoQ10 attenuate the severity of collagen-induced arthritis (CIA) and show an additive effect in a mouse model. The combination of Met and CoQ10 improved CIA, reducing joint inflammation, Th17 differentiation and IgG production. In contrast, the combination of Met and CoQ10 induced Treg differentiation. Osteoclastogenesis was reduced by the combination of Met and CoQ10. The protein expression of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha in mice splenocytes exposed to lipopolysaccharide decreased after drug combination therapy. We also found that the expression of JC 1 and COX IV were enhanced by treatment with the combination of Met and CoQ10. Moreover, the combination of Met and CoQ10 promoted mitochondrial O2 consumption. These findings suggest that the combination of Met and CoQ10 reduced CIA severity, improving mitochondrial dysfunction compared to Met or CoQ10 alone. These results present a novel, significant preventive targets in RA and may enhance our understanding of its pathogenesis. PMID- 26681427 TI - Adolescent and Young Adult Patient Engagement and Participation in Survey-Based Research: A Report From the "Resilience in Adolescents and Young Adults With Cancer" Study. AB - Conducting patient-reported outcomes research with adolescents and young adults (AYAs) is difficult due to low participation rates and high attrition. Forty seven AYAs with newly diagnosed cancer at two large hospitals were prospectively surveyed at the time of diagnosis and 3-6 and 12-18 months later. A subset participated in 1:1 semistructured interviews. Attrition prompted early study closure at one site. The majority of patients preferred paper-pencil to online surveys. Interview participants were more likely to complete surveys (e.g., 93% vs. 58% completion of 3-6 month surveys, P = 0.02). Engaging patients through qualitative methodologies and using patient-preferred instruments may optimize future research success. PMID- 26681428 TI - Guidelines for studying developmental prosopagnosia in adults and children. AB - Developmental prosopagnosia (DP) is a neurodevelopmental condition characterized by severe face identity recognition problems that results from a failure to develop the mechanisms necessary for adequate face processing (Duchaine BC, Nakayama K. Developmental prosopagnosia: a window to content-specific face processing. Curr Opin Neurobiol 2006, 16:166-173.). It occurs in children and adults with normal visual acuity, and without intellectual impairments or known brain injuries. Given the importance of face recognition in daily life, and the detrimental effects of impaired face recognition, DP is an important area of study. Yet conventions for classifying individuals as DP for research purposes are poorly defined. In this focus paper, we discuss: (1) criteria for an operational definition of DP; 2) tests of face recognition and conventions for classifying individuals as DP; and 3) important considerations regarding common associations and dissociations, and cognitive heterogeneity in DP. We also highlight issues unique to studying DP in children, a relatively new endeavor that is proving to be an important complement to the work with adults. Ultimately, we hope to identify challenges researchers face when studying DP, and offer guidelines for others to consider when embarking on their own research pursuits on the topic. For further resources related to this article, please visit the WIREs website. PMID- 26681392 TI - Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age Related Macular Degeneration Treatments Trials (CATT). AB - PURPOSE: To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. DESIGN: Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). PARTICIPANTS: Patients with NVAMD. METHODS: Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra retinal leakage of fluorescein in combination with other associated features. MAIN OUTCOME MEASURES: Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years. RESULTS: Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P < 0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 MUm vs. -161 MUm; P < 0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P < 0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025). CONCLUSIONS: At both 1 and 2 years after initiation of anti-VEGF treatment in CATT, eyes with RAP were less likely to have fluid, FA leakage, scar, and SHRM and more likely to have GA than eyes without RAP. Mean improvement in VA was similar at 2 years. PMID- 26681429 TI - PRISM: Phase 2 trial with panitumumab monotherapy as second-line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. AB - BACKGROUND: Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer (PRISM) trial evaluated the safety and efficacy of panitumumab as second line monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: This was an open-label, single-arm, multicenter trial that enrolled patients with progressive disease or intolerance to first-line systemic chemotherapy for recurrent or metastatic SCCHN. Patients received panitumumab 9 mg/kg Q3W. The primary endpoint was overall response rate; secondary endpoints included disease control rate, overall survival (OS), progression-free survival (PFS), and safety. RESULTS: The overall response rate was 4% (2 of 51 patients) and the disease control rate was 39% (20 of 51 patients). Median PFS was 1.4 months (95% confidence interval [CI] = 1.3-2.4 months). Median OS was 5.1 months (95% CI = 4.3-8.3 months). The most common adverse events were rash/dermatitis acneiform (69%), fatigue (33%), dry skin (21%), and hypomagnesemia (21%). There was one treatment-related death (angioedema). CONCLUSION: Panitumumab monotherapy had limited activity in previously treated patients with recurrent or metastatic SCCHN. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1756-E1761, 2016. PMID- 26681426 TI - Fundamentals of protein interaction network mapping. AB - Studying protein interaction networks of all proteins in an organism ("interactomes") remains one of the major challenges in modern biomedicine. Such information is crucial to understanding cellular pathways and developing effective therapies for the treatment of human diseases. Over the past two decades, diverse biochemical, genetic, and cell biological methods have been developed to map interactomes. In this review, we highlight basic principles of interactome mapping. Specifically, we discuss the strengths and weaknesses of individual assays, how to select a method appropriate for the problem being studied, and provide general guidelines for carrying out the necessary follow-up analyses. In addition, we discuss computational methods to predict, map, and visualize interactomes, and provide a summary of some of the most important interactome resources. We hope that this review serves as both a useful overview of the field and a guide to help more scientists actively employ these powerful approaches in their research. PMID- 26681430 TI - Osteotomising the fibular free flap: an anatomical perspective. AB - Multiple osteotomies with the help of 3-dimensional planning have improved the accuracy of reconstructions, and the reliability and versatility of the fibular free flap is well recognised. To investigate the periosteal blood supply of the fibula and to define safe limits for the size of bony segments, we performed a cadaveric study on 10 fresh frozen lower limbs using a combined barium latex mixture. We modelled cuts at intervals of 1.0, 1.5, and 2.0cm, and assessed the number of periosteal vessels. After virtual dissections using DICOM data obtained from high-resolution computed tomograms (CT), on average we found 12.8 periosteal branches, with a mean (SD) distance between them of 1.36 (0.18)cm. In 34.9% of the 1cm segments there were no visible periosteal vessels. Vascularity seemed to be more reliable in longer segments, with 83.4% of those 1.5cm long, and 94% of those of over 2cm containing at least one branch. PMID- 26681431 TI - Impact of prescription charges on people living in poverty: A qualitative study. AB - BACKGROUND: Prescription charges or copayments have been shown to reduce consumption of medicines. For people living in poverty, prescription charges can prevent them from getting the medicines they need, and this can result in poorer health status. Prescription charges are low in New Zealand compared to many other countries, but those living in poverty are not exempt from fees. OBJECTIVES: The aim of this study was to explore the lived experience of people who struggle to pay prescription charges and to propose a model for how being unable to afford prescription charges might affect health. METHODS: Participants were recruited through organizations that provide services entirely or predominantly to low income persons. Semi-structured interviews were carried out with 29 people who had been identified as having problems paying for prescriptions. Approximately half of the sample population was Maori (indigenous New Zealanders). Ethical approval was obtained from the University of Otago. RESULTS: Participants reported having to make difficult decisions when picking up their prescription medicines. These included choosing some medicines and leaving others, such as choosing medicines for mental health rather than physical health; cutting food consumption or eating less healthy food so as to pay for medicines; or picking up medicines for children while leaving those for adults. Participants also reported strategies like reducing doses to make prescriptions last longer; and delaying picking up medicines. These led to sub-optimal dosing or interrupted treatment. CONCLUSIONS: Even low financial barriers can have a significant impact on low income people's access to medicines and reduce the effectiveness of treatment. Not being able to afford prescription medicines may impact negatively on people's health directly by preventing access to medicines, through reducing expenditure on other items need for health, and by potentiating stigma. PMID- 26681433 TI - [Current situation of the research on living conditions and health status of elderly people in Spain]. AB - OBJECTIVE: To analyse the dimensions studied with respect to living and health conditions of the non-institutionalised elderly in the scientific literature in Spain. METHOD: A content analysis based on secondary sources was carried out by literature searches in Pubmed and Embase in Spanish and English. The search strategies combined terms related to older people, health and/or living conditions and with Spain. All studies assessing living and/or health conditions of elderly in Spain were included. Studies analyzing a specific aspect of living or health conditions and those based on institutionalized population were excluded. RESULTS: A total of 14 studies were considered in the content analysis. The studies are usually local, cross-sectional and data collection is done by direct interview. Variability was observed in the aspects analysed about living and health conditions. All studies included: sociodemographic characteristics, health status and lifestyle habits. Issues related to the status of the out-of home environment are poorly analysed. CONCLUSIONS: This work allows knowing the dimensions prioritised in the studies carried out to date about health and living conditions in Spain. It also provides key elements for the development of future research aiming to integrate both living and health conditions of elderly population, both aspects closely related. PMID- 26681432 TI - Measuring the economic value of morning stiffness: consistency over 1 year. AB - OBJECTIVES: The aims of this study were to determine the within-patient variation in the duration of morning stiffness (MS) over 1 year and the corresponding monetary equivalents assigned to its changes using the willingness-to-pay (WTP) methodology. METHOD: A sample of 100 patients with rheumatoid arthritis (RA) was drawn from the register of the Hospital District of Southwest Finland. Subjects were interviewed by telephone on recruitment and 1 year later, using the same structured questionnaire. The subjects were asked to estimate in minutes the typical duration of their MS during the previous week. Sociodemographic background data and subjects' WTP for a 25, 50, 75, and 100% reduction in MS duration were requested, and years with RA diagnosis and serological data were obtained from hospital records. RESULTS: After 1 year, there was a reduction in average MS duration from 44.7 min to 39.0 min (ns); duration was reduced in 35% of patients, unchanged in 35%, and prolonged in 30%. Changes in MS duration were reflected by within-patient variation in WTP estimates. In linear regression models, change in duration of MS significantly (p < 0.03) explained the variation in change of WTP for symptom reduction. CONCLUSIONS: WTP methodology produces consistent monetary values to assess the relative values patients with RA place on reduction in duration of MS. PMID- 26681434 TI - Development and characterization of polymorphic microsatellite loci for spiny footed lizards, Acanthodactylus scutellatus group (Reptilia, Lacertidae) from arid regions. AB - BACKGROUND: Spiny-footed lizards constitute a diverse but scarcely studied genus. Microsatellite markers would help increasing the knowledge about species boundaries, patterns of genetic diversity and structure, and gene flow dynamics. We developed a set of 22 polymorphic microsatellite loci for cross-species amplification in three taxa belonging to the Acanthodactylus scutellatus species group, A. aureus, A. dumerili/A. senegalensis and A. longipes, and tested the same markers in two other members of the group, A. scutellatus and A. taghitensis. RESULTS: Amplifications in A. aureus, A. longipes and A. dumerili/A. senegalensis were successful, with markers exhibiting a number of alleles varying between 1 and 19. Expected and observed heterozygosity ranged, respectively, between 0.046-0.893 and 0.048-1.000. Moreover, 17 and 16 loci were successfully amplified in A. scutellatus and A. taghitensis, respectively. CONCLUSION: These markers are provided as reliable genetic tools to use in future evolutionary, behavioural and conservation studies involving species from the A. scutellatus group. PMID- 26681435 TI - Cisplatin-Based Chemotherapy for Testicular Germ Cell Tumors: Complication Rates of Peripheral versus Central Venous Administration. AB - OBJECTIVE: Despite the low local toxicity of the used agents, Cisplatin-based chemotherapy (CBP) for patients with testicular germ cell tumors (TGCT) is mostly delivered via a central venous access (CVA). Since 2008, CBP is given peripherally in our hospital. METHODS: Medical reports of TGCT patients who received CBP between September 1991 and August 2014 were evaluated. Complications regarding the way of administration (CVA vs. peripheral venous catheter [PVC]) were classified according to the Common Terminology Criteria of Adverse Events. The complication rates were compared using chi square test and propensity score matching. RESULTS: During 288 cycles in 109 patients, 85 complications (29.5%) were observed with similar rates for overall (PVC 31.3%, CVA 29.9%; p = 0.820) and grade I complications (21.3%, 25.4%; p = 0.470). More grade II complications were observed in the PVC group (10.0 vs. 1.5%; p < 0.001). Grade III complications requiring invasive treatment were found only in the CVA group (3.0%; p = 0.120). Using propensity score matching, no differences in overall (p = 0.950), grade I (p = 0.540) and grades II/III (p = 0.590) complications were seen. CONCLUSION: The peripheral and central administration of CBP has similar overall complication rates. Despite more grade II complications, the peripheral administration of CBP is a safe alternative for TGCT patients. Additionally, no severe grade III complications occurred. PMID- 26681437 TI - Correction: Spatial Variation of the Gut Microbiota in Broiler Chickens as Affected by Dietary Available Phosphorus and Assessed by T-RFLP Analysis and 454 Pyrosequencing. PMID- 26681436 TI - Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis. AB - Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ? 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ? 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification. PMID- 26681438 TI - Early experience with X-ray magnetic resonance fusion for low-flow vascular malformations in the pediatric interventional radiology suite. AB - This technical innovation describes our experience using an X-ray magnetic resonance fusion (XMRF) software program to overlay 3-D MR images on real-time fluoroscopic images during sclerotherapy procedures for vascular malformations at a large pediatric institution. Five cases have been selected to illustrate the application and various clinical utilities of XMRF during sclerotherapy procedures as well as the technical limitations of this technique. The cases demonstrate how to use XMRF in the interventional suite to derive additional information to improve therapeutic confidence with regards to the extent of lesion filling and to guide clinical management in terms of intraprocedural interventional measures. PMID- 26681439 TI - Hanging suicides in northern Finland: A descriptive epidemiological study. AB - The authors examined all hanging-suicides during 1988-2013 (N = 851) in the province of Oulu, northern Finland. Using death-certificate data and ICD diagnoses from the Finnish Hospital Discharge Register, we focused on gender differences in suicide, mental health, and somatic health. Male victims were more likely to have intoxication or problematic alcohol use; female victims were more likely to have somatic or mental hospitalization. Previous physical or mental hospitalization was related with absence of intoxication at the time of suicide. Suicide prevention should focus on acute alcohol abuse in the presence of acute stressors, suicidal thoughts and mental illness. PMID- 26681440 TI - Online Outreach Services Among Men Who Use the Internet to Seek Sex With Other Men (MISM) in Ontario, Canada: An Online Survey. AB - BACKGROUND: Men who use the Internet to seek sex with other men (MISM) are increasingly using the Internet to find sexual health information and to seek sexual partners, with some research suggesting HIV transmission is associated with sexual partnering online. Aiming to "meet men where they are at," some AIDS service organizations (ASOs) deliver online outreach services via sociosexual Internet sites and mobile apps. OBJECTIVE: To investigate MISM's experiences and self-perceived impacts of online outreach. METHODS: From December 2013 to January 2014, MISM aged 16 years or older were recruited from Internet sites, mobile apps, and ASOs across Ontario to complete a 15-minute anonymous online questionnaire regarding their experience of online outreach. Demographic factors associated with encountering online outreach were assessed using backward stepwise multivariable logistic regression (P<.05 was considered significant). RESULTS: Of 1830 MISM who completed the survey, 8.25% (151/1830) reported direct experience with online outreach services. Encountering online outreach was more likely for Aboriginal versus white MISM, MISM from Toronto compared with MISM from either Eastern or Southwestern Ontario, and MISM receiving any social assistance. MISM who experienced online outreach felt the service provider was friendly (130/141, 92.2%), easy to understand (122/140, 87.1%), helpful (115/139, 82.7%), prompt (107/143, 74.8%), and knowledgeable (92/134, 68.7%); half reported they received a useful referral (49/98, 50%). Few MISM felt the interaction was annoying (13/141, 9.2%) or confusing (18/142, 12.7%). As a result of their last online outreach encounter, MISM reported the following: better understanding of (88/147, 59.9%) and comfort with (75/147, 51.0%) their level of sexual risk; increased knowledge (71/147, 48.3%); and feeling less anxious (51/147, 34.7%), better connected (46/147, 31.3%), and more empowered (40/147, 27.2%). Behaviorally, they reported using condoms more frequently (48/147, 32.7%) and effectively (35/147, 23.8%); getting tested for HIV (43/125, 34.4%) or STIs (42/147, 28.6%); asking for their partners' HIV statuses (37/147, 25.2%); and serosorting (26/147, 17.7%). Few MISM reported no changes (15/147, 10.2%) and most would use these services again (98/117, 83.8%). Most MISM who did not use online outreach said they did not need these services (1074/1559, 68.89%) or were unaware of them (496/1559, 31.82%). CONCLUSIONS: This is the first online outreach evaluation study of MISM in Canada. Online outreach services are a relatively new and underdeveloped area of intervention, but are a promising health promotion strategy to provide service referrals and engage diverse groups of MISM in sexual health education. PMID- 26681442 TI - Heparin Versus Bivalirudin Monotherapy in the Setting of Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction. AB - OBJECTIVE: To evaluate direct comparisons of bivalirudin versus unfractionated heparin (UFH) as anticoagulants during ST-segment elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PPCI). DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-September 2015), International Pharmaceutical Abstracts (1960-September 2015), and Cochrane Databases (publications archived until September 2015) using the terms bivalirudin, unfractionated heparin, ST-segment elevation myocardial infarction, and primary percutaneous coronary intervention. STUDY SELECTION AND DATA EXTRACTION: English-language randomized controlled trials and meta-analyses were eligible for inclusion for data review of STEMI where PPCI was performed. DATA SYNTHESIS: Either bivalirudin or UFH is recommended in the setting of STEMI where PPCI is to be performed. Bivalirudin is touted for its predictable pharmacokinetics, effects on thrombin-mediated platelet inhibition, and favorable outcomes with regard to adverse bleeding profiles, whereas UFH, the gold standard anticoagulant during PPCI, remains a viable treatment strategy. Only recently have direct comparisons of UFH and bivalirudin during PPCI become available. The evidence available is complicated by variances in use of glycoprotein IIb/IIIa inhibitors (GPIs), P2Y12 inhibitors, access sites, and anticoagulant dosing strategies. We provide a review of contemporary trials and advancements in this area. CONCLUSIONS: When compared to UFH with limited use of GPI, available evidence demonstrates that bivalirudin reduces bleeding at the expense of increasing risk for acute stent thrombosis. Further randomized studies are needed to determine the potential benefits of a post-PCI infusion of bivalirudin to reduce the risk for acute stent thrombosis, long-term follow-up beyond 30 days, and mortality. PMID- 26681443 TI - Evaluation of Pharmacist Medication Education and Post-discharge Follow-up in Reducing Readmissions in Patients With ST-Segment Elevation Myocardial Infarction (STEMI). AB - BACKGROUND: Hospital readmissions have been shown to contribute to both patient morbidity and rising health care expenditures across a number of disease processes. Adherence to a cardioprotective drug regimen is particularly important after ST-segment elevated myocardial infarction (STEMI) because it is an acute condition associated with high patient morbidity and mortality. OBJECTIVE: The objective of this study was to evaluate the effectiveness of pharmacist intervention with regard to reduction in hospital readmissions and improvement in medication adherence and literacy. METHODS: This was a prospective single-center study in which patients admitted with STEMI who received stents between January 2015 and April 2015 were included. Pharmacist intervention included medication reconciliation, medication education, facilitation of the delivery of discharge medications, and post-discharge telephone calls within 48 to 72 hours. A retrospective review of historical STEMI patients who did not have pharmacist transitions of care support was performed to compare readmission rates. RESULTS: All-cause readmission at 30 days decreased from 13% to 5% (P = 0.18). Twelve of 95 patients in the historical control group were readmitted, compared to 2 of 40 patients in the intervention group. In the historical group, 3 of 12 patients required subsequent stent placement upon readmission, compared to none in the intervention group., Medication adherence and literacy scores improved significantly from baseline to high adherence and literacy at 30 days post discharge (P = 0.0005). CONCLUSION: Pharmacist involvement in medication education signficantly improved medication adherence and literacy. There was a reduction in 30-day readmission rates, but the results were not statistically significant. PMID- 26681441 TI - Transcriptome profiling of bovine inner cell mass and trophectoderm derived from in vivo generated blastocysts. AB - BACKGROUND: This study describes the generation and analysis of the transcriptional profile of bovine inner cell mass (ICM) and trophectoderm (TE), obtained from in vivo developed embryos by using a bovine-embryo specific array (EmbryoGENE) containing 37,238 probes. RESULTS: A total of 4,689 probes were differentially expressed between ICM and TE, among these, 2,380 and 2,309 probes were upregulated in ICM and TE tissues, respectively (P <= 0.01, FC >= 2.0, FDR: 2.0). Ontological classification of the genes predominantly expressed in ICM emerged a range of functional categories with a preponderance of genes involved in basal and developmental signaling pathways including P53, TGFbeta, IL8, mTOR, integrin, ILK, and ELF2 signalings. Cross-referencing of microarray data with two available in vitro studies indicated a marked reduction in ICM vs. TE transcriptional difference following in vitro culture of bovine embryos. Moreover, a great majority of genes that were found to be misregulated following in vitro culture of bovine embryos were known genes involved in epigenetic regulation of pluripotency and cell differentiation including DNMT1, GADD45, CARM1, ELF5 HDAC8, CCNB1, KDM6A, PRDM9, CDX2, ARID3A, IL6, GADD45A, FGFR2, PPP2R2B, and SMARCA2. Cross-species referencing of microarray data revealed substantial divergence between bovine and mouse and human in signaling pathways involved in early lineage specification. CONCLUSIONS: The transcriptional changes occur during ICM and TE lineages specification in bovine is greater than previously understood. Therefore, this array data establishes a standard to evaluate the in vitro imprint on the transcriptome and to hypothesize the cross species differences that allow in vitro acquisition of pluripotent ICM in human and mice but hinder that process in bovine. PMID- 26681444 TI - Medication Regimen Complexity and Polypharmacy as Factors Associated With All Cause Mortality in Older People: A Population-Based Cohort Study. AB - OBJECTIVES: To investigate whether medication regimen complexity and/or polypharmacy are associated with all-cause mortality in older people. METHODS: This was a population-based cohort study among community-dwelling and institutionalized people >=60 years old (n = 3348). Medication regimen complexity was assessed using the 65-item Medication Regimen Complexity Index (MRCI) in 10 unit steps. Polypharmacy was assessed as a continuous variable (number of medications). Mortality data were obtained from the Swedish National Cause of Death Register. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% CIs for the association between regimen complexity and polypharmacy with all-cause mortality over a 3-year period. Subanalyses were performed stratifying by age (<=80 and>80 years), sex, and cognition (Mini-Mental State Examination [MMSE] <26 and >=26). RESULTS: During follow-up, 14% of the participants (n = 470) died. After adjusting for age, sex, comorbidity, educational level, activities of daily living, MMSE, and residential setting, a higher MRCI was associated with mortality (adjusted HR = 1.12; 95% CI = 1.01-1.25). Polypharmacy was not associated with mortality (adjusted HR = 1.03; 95% CI = 0.99-1.06). When stratifying by sex, both MRCI and polypharmacy were associated with mortality in men but not in women. MRCI was associated with mortality in participants <=80 years old and in participants with MMSE >=26 but not in participants >80 years old or with MMSE <26. CONCLUSION: Regimen complexity was a better overall predictor of mortality than polypharmacy. However, regimen complexity was not predictive of mortality in women, in participants >80 years old, or in those with MMSE<26. These different associations with mortality deserve further investigation. PMID- 26681445 TI - Pilonidal sinus disease guidelines: a minefield? PMID- 26681447 TI - Construction and Characterization of Protein-Encapsulated Electrospun Fibermats Prepared from a Silica/Poly(gamma-glutamate) Hybrid. AB - Protein-encapsulated fibermats are an attractive platform for protein-based bioactive materials. However, the choice of methods is still limited and not applicable to a wide range of proteins. In this study, we studied new polymeric materials for constructing protein-encapsulated fibermats, in which protein molecules are encapsulated within the nanofibers of fibermats without causing deleterious changes to protein structure or function. We constructed a protein encapsulated fibermat using the poly(gamma-glutamate) (PGA)/(3-glycidyloxypropyl) trimethoxysilane (GPTMS) hybrid as a precursor for electrospinning. Because the PGA/GPTMS hybrid is water-soluble, protein molecules can be added to the precursor in an aqueous solution, significantly enhancing protein stability. Polycondensation during electrospinning (in-flight polycondensation) makes the obtained fibermats water-insoluble, which stabilizes the fibermat structure such that it is resistant to degradation in aqueous buffer. The molecular structure of the PGA/GPTMS hybrid gives rise to unique molecular permeability, which alters the selectivity and specificity of biochemical reactions involving the encapsulated enzymes; lower molecular-weight (MW) substrates can permeate the nanofibers, promoting enzyme activity, but higher MW substrates such as inhibitor peptides cannot permeate the nanofibers, suppressing enzyme activity. We present an effective method of encapsulating bioactive molecules while maintaining their structure and function, increasing the versatility of electrospun fibermats for constructing various bioactive materials. PMID- 26681448 TI - Verbal cues effectively orient children's auditory attention in a CV-syllable dichotic listening paradigm. AB - In their groundbreaking work featuring verbal dichotic listening tasks, Mondor and Bryden showed that tone cues do not enhance children's attentional orienting, in contrast to adults. The magnitude of the children's right-ear advantage was not attenuated when their attention was directed to the left ear. Verbal cues did, however, appear to favour the orientation of attention at around 10 years, although stimulus-onset asynchronies (SOAs), which ranged between 450 and 750 ms, were not rigorously controlled. The aim of our study was therefore to investigate the role of both types of cues in a typical CV-syllable dichotic listening task administered to 8- to 10-year-olds, applying a protocol as similar as possible to that used by Mondor and Bryden, but controlling for SOA as well as for cued ear. Results confirmed that verbal cues are more effective than tone cues in orienting children's attention. However, in contrast to adults, no effect of SOA was observed. We discuss the relative difficulty young children have processing CV syllables, as well as the role of top-down processes in attentional orienting abilities. PMID- 26681446 TI - GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function. AB - Degeneration of nigrostriatal dopaminergic system is the principal lesion in Parkinson's disease. Because glial cell line-derived neurotrophic factor (GDNF) promotes survival of dopamine neurons in vitro and in vivo, intracranial delivery of GDNF has been attempted for Parkinson's disease treatment but with variable success. For improving GDNF-based therapies, knowledge on physiological role of endogenous GDNF at the sites of its expression is important. However, due to limitations of existing genetic model systems, such knowledge is scarce. Here, we report that prevention of transcription of Gdnf 3'UTR in Gdnf endogenous locus yields GDNF hypermorphic mice with increased, but spatially unchanged GDNF expression, enabling analysis of postnatal GDNF function. We found that increased level of GDNF in the central nervous system increases the number of adult dopamine neurons in the substantia nigra pars compacta and the number of dopaminergic terminals in the dorsal striatum. At the functional level, GDNF levels increased striatal tissue dopamine levels and augmented striatal dopamine release and re-uptake. In a proteasome inhibitor lactacystin-induced model of Parkinson's disease GDNF hypermorphic mice were protected from the reduction in striatal dopamine and failure of dopaminergic system function. Importantly, adverse phenotypic effects associated with spatially unregulated GDNF applications were not observed. Enhanced GDNF levels up-regulated striatal dopamine transporter activity by at least five fold resulting in enhanced susceptibility to 6-OHDA, a toxin transported into dopamine neurons by DAT. Further, we report how GDNF levels regulate kidney development and identify microRNAs miR-9, miR-96, miR-133, and miR-146a as negative regulators of GDNF expression via interaction with Gdnf 3'UTR in vitro. Our results reveal the role of GDNF in nigrostriatal dopamine system postnatal development and adult function, and highlight the importance of correct spatial expression of GDNF. Furthermore, our results suggest that 3'UTR targeting may constitute a useful tool in analyzing gene function. PMID- 26681449 TI - Erratum: Tristetraprolin regulation of interleukin-22 production. PMID- 26681451 TI - Plasma protein thiols: an early marker of oxidative stress in asthma and chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n = 24) and mild stable COPD (n = 29) and in age- and sex-matched controls. Forced expiratory volume in 1 s (FEV1 ) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (rho = 0.49, P = 0.007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR = 0.32, 95% CI 0.13-0.78, P = 0.01) and COPD (OR = 0.50, 95% CI 0.26-0.95, P = 0.03). These findings suggest that proteins -SH are a sensitive OS marker in early COPD and asthma. PMID- 26681450 TI - Gene structure and evolution of transthyretin in the order Chiroptera. AB - Bats are mammals in the order Chiroptera. Although many extensive morphologic and molecular genetics analyses have been attempted, phylogenetic relationships of bats has not been completely resolved. The paraphyly of microbats is of particular controversy that needs to be confirmed. In this study, we attempted to use the nucleotide sequence of transthyretin (TTR) intron 1 to resolve the relationship among bats. To explore its utility, the complete sequences of TTR gene and intron 1 region of bats in Vespertilionidae: genus Eptesicus (Eptesicus fuscus) and genus Myotis (Myotis brandtii, Myotis davidii, and Myotis lucifugus), and Pteropodidae (Pteropus alecto and Pteropus vampyrus) were extracted from the retrieved sequences, whereas those of Rhinoluphus affinis and Scotophilus kuhlii were amplified and sequenced. The derived overall amino sequences of bat TTRs were found to be very similar to those in other eutherians but differed from those in other classes of vertebrates. However, missing of amino acids from N terminal or C-terminal region was observed. The phylogenetic analysis of amino acid sequences suggested bat and other eutherian TTRs lineal descent from a single most recent common ancestor which differed from those of non-placental mammals and the other classes of vertebrates. The splicing of bat TTR precursor mRNAs was similar to those of other eutherian but different from those of marsupial, bird, reptile and amphibian. Based on TTR intron 1 sequence, the inferred evolutionary relationship within Chiroptera revealed more closely relatedness of R. affinis to megabats than to microbats. Accordingly, the paraphyly of microbats was suggested. PMID- 26681452 TI - Whole-Exome Sequencing in Nine Monozygotic Discordant Twins. AB - By definition, monozygotic (MZ) twins carry an identical set of genetic information. The observation of early post-twinning mutational events was shown to cause phenotypic discordance among MZ twin pairs. These mutational events comprise genomic alterations at different scales, ranging from single nucleotide changes to larger copy-number variations (CNVs) of varying sizes, as well as epigenetic changes. Here, we performed whole-exome sequencing (WES) in nine discordant MZ twins to identify somatic mutational events in the affected twin that might exert a dominant negative effect. Five of these MZ twin pairs were discordant for congenital heart defects (CHD), two for endocrine disorders, one for omphalocele, and one for congenital diaphragmatic hernia (CDH). Analysis of WES data from all nine MZ twin pairs using the de novo probability tool DeNovoGear detected only one apparent de novo variation in TMPRSS13 in one of the CHD-affected twins. Analysis of WES data from all nine MZ twin pairs by using standard filter criteria without the de novo probability tool DeNovoGear revealed a total of 6,657 variations in which both the twin pairs differed. After filtering for variations only present in the affected twins and absent in in house controls, 722 variations remained. Visual inspection for read quality decreased this number to 12, present only in the affected twin. However, Sanger sequencing of the overall 13 variations failed to confirm the variation in the affected twin. These results suggest that somatic mutational events in coding regions do not seem to play a major role in the phenotypic expression of MZ discordant twin pairs. PMID- 26681453 TI - US device industry and FDA "colluded" on legislation to weaken regulatory oversight. PMID- 26681455 TI - A complex cell. PMID- 26681454 TI - Discovery of novel INK4C small-molecule inhibitors to promote human and murine hematopoietic stem cell ex vivo expansion. AB - Hematopoietic stem cells (HSCs) have emerged as promising therapeutic cell sources for high-risk hematological malignancies and immune disorders. However, their clinical use is limited by the inability to expand these cells ex vivo. Therefore, there is an urgent need to identify specific targets and effective probes that can expand HSCs. Here we report a novel class of INK4C (p18(INK4C) or p18) small molecule inhibitors (p18SMIs), which were initially found by in silico 3D screening. We identified a lead p18 inhibitor, XIE18-6, confirmed its p18 targeting specificity and bioactivity of promoting HSCs expansion, and then performed structure-activity relationship (SAR) studies by synthesizing a series of analogs of XIE18-6. Among these, compound 40 showed the most potent bioactivity in HSCs expansion (ED50 = 5.21 nM). We confirmed that compound 40 promoted expansion of both murine and human HSCs, and also confirmed its p18 targeting specificity. Notably, compound 40 did not show significant cytotoxicity toward 32D cells or HSCs, nor did it augment leukemia cell proliferation. Taken together, our newly discovered p18SMIs represent novel chemical agents for murine and human HSCs ex vivo expansion and also can be used as valuable chemical probes for further HSC biology research towards promising utility for therapeutic purposes. PMID- 26681456 TI - The development and maintenance of resident macrophages. AB - The molecular and cellular mechanisms that underlie the many roles of macrophages in health and disease states in vivo remain poorly understood. The purpose of this Review is to present and discuss current knowledge on the developmental biology of macrophages, as it underlies the concept of a layered myeloid system composed of 'resident' macrophages that originate mainly from progenitor cells generated in the yolk sac and of 'passenger' or 'transitory' myeloid cells that originate and renew from bone marrow hematopoietic stem cells, and to provide a framework for investigating the functions of macrophages in vivo. PMID- 26681457 TI - Tissue biology perspective on macrophages. AB - Macrophages are essential components of mammalian tissues. Although historically known mainly for their function in host defense and the clearance of apoptotic cells, macrophages are now increasingly recognized as serving many roles in tissue development, homeostasis and repair. In addition, tissue-resident macrophages have many tissue-specific functional characteristics, which are a reflection of distinct gene-expression programs. Here we discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives. PMID- 26681458 TI - The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis. AB - Macrophages provide a critical systemic network cells of the innate immune system. Emerging data suggest that in addition, they have important tissue specific functions that range from clearance of surfactant from the lungs to neuronal pruning and establishment of gut homeostasis. The differentiation and tissue-specific activation of macrophages require precise regulation of gene expression, a process governed by epigenetic mechanisms such as DNA methylation, histone modification and chromatin structure. We argue that epigenetic regulation of macrophages is determined by lineage- and tissue-specific transcription factors controlled by the built-in programming of myeloid development in combination with signaling from the tissue environment. Perturbation of epigenetic mechanisms of tissue macrophage identity can affect normal macrophage tissue function and contribute to pathologies ranging from obesity and autoimmunity to neurodegenerative diseases. PMID- 26681459 TI - Molecular control of activation and priming in macrophages. AB - In tissues, macrophages are exposed to metabolic, homeostatic and immunoregulatory signals of local or systemic origin that influence their basal functions and responses to danger signals. Signal-transduction pathways regulated by extracellular signals are coupled to distinct sets of broadly expressed stimulus-regulated transcription factors whose ability to elicit gene-expression changes is influenced by the accessibility of their binding sites in the macrophage genome. In turn, accessibility of macrophage-specific transcriptional regulatory elements (enhancers and promoters) is specified by transcription factors that determine the macrophage lineage or impose their tissue-specific properties. Here we review recent findings that advance the understanding of mechanisms underlying priming and signal-dependent activation of macrophages and discuss the effect of genetic variation on these processes. PMID- 26681461 TI - Glycolysis and EZH2 boost T cell weaponry against tumors. PMID- 26681460 TI - New insights into the multidimensional concept of macrophage ontogeny, activation and function. AB - Macrophages have protective roles in immunity to pathogens, tissue development, homeostasis and repair following damage. Maladaptive immunity and inflammation provoke changes in macrophage function that are causative of disease. Despite a historical wealth of knowledge about macrophages, recent advances have revealed unknown aspects of their development and function. Following development, macrophages are activated by diverse signals. Such tissue microenvironmental signals together with epigenetic changes influence macrophage development, activation and functional diversity, with consequences in disease and homeostasis. We discuss here how recent discoveries in these areas have led to a multidimensional concept of macrophage ontogeny, activation and function. In connection with this, we also discuss how technical advances facilitate a new roadmap for the isolation and analysis of macrophages at high resolution. PMID- 26681462 TI - Putting the brakes on ILC2 cells. PMID- 26681463 TI - The cell identity of cytotoxic T lymphocytes. PMID- 26681470 TI - Ligand-Mediated and Copper-Catalyzed C(sp(3))-H Bond Functionalization of Aryl Ketones with Sodium Sulfinates under Mild Conditions. AB - A novel and convenient copper (II) bromide and 1,8-diazabicyclo[5.4.1]undec-7-ene (DBU) or 1,10-phenanthroline catalysis protocol for the construction of alpha alkyl-beta-keto sulfones via C(sp(3))-H bond functionalization followed by C(sp(3))-S bond formation between aryl ketones and sodium sulfinates at room temperature has been developed. This method is applicable to a wide range of aryl ketones and sodium sulfinates. The electronic effects of aryl ketones and ligands effects of the copper salts are crucial for this transformation. Typically, substituted aryl ketones with electron-withdrawing group do not need any ligand to give a good to excellent yield, while substituted aryl ketones with electron donating group and electron-rich heteroaromatic ketones offer a good to excellent yield only under the nitrogen-based ligands. The practical value of this transformation highlights the efficient and robust one-pot synthesis of alpha alkyl-beta-keto sulfones. PMID- 26681471 TI - It's Not Appendicitis! PMID- 26681472 TI - For Children with Medical Complexity, There Is No Place Like (The Medical) Home. PMID- 26681473 TI - Continuous and Dichotomous Metabolic Syndrome Definitions in Youth Predict Adult Type 2 Diabetes and Carotid Artery Intima Media Thickness: The Cardiovascular Risk in Young Finns Study. AB - OBJECTIVES: To examine the utility of continuous metabolic syndrome (cMetS) scores vs a dichotomous metabolic syndrome (MetS) definition in youth to predict adult type 2 diabetes mellitus (T2DM) and carotid intima-media thickness (IMT). STUDY DESIGN: Participants (n = 1453) from the population-based, prospective, observational Cardiovascular Risk in Young Finns Study who were examined in youth (when aged 9-18 years) and re-examined 15-25 years later. Four cMetS scores were constructed according to procedures most often used in the literature that comprised the youth risk factor inputs of body mass index, blood pressure, glucose, insulin, high-density lipoprotein-cholesterol, and triglycerides. Adult outcomes included T2DM and high carotid IMT (>= 90 th percentile). RESULTS: For a 1 SD increase in cMetS scores in youth, participants had a 30%-78% increased risk of T2DM and 12%-61% increased risk of high carotid IMT. Prediction of adult T2DM and high carotid IMT using cMetS scores in youth was essentially no different to a dichotomous MetS definition with area under the receiver-operating characteristic curve ranging from 0.54-0.60 (continuous definitions) and 0.55 0.59 (dichotomous) with 95% CIs often including 0.5, and integrated discrimination improvement from -0.2% to -0.6%. CONCLUSIONS: cMetS scores in youth are predictive of cardiometabolic outcomes in adulthood. However, they do not have increased predictive utility over a dichotomous definition of MetS. PMID- 26681474 TI - Fibromyalgia--Toward a Definition in Children. PMID- 26681475 TI - Modern Neuroimaging: Deciphering the Developing Brain. PMID- 26681476 TI - Parent and Adolescent Views on Barriers to Adolescent Preventive Health Care Utilization. AB - OBJECTIVES: To determine adolescent and parent views of barriers to annual adolescent preventive care. STUDY DESIGN: A nationally recruited cross-sectional study of adolescents between ages 13 and 18 years, and parents of adolescents from different families, were recruited. The primary outcome was self-report of preventive care in the last 12 months. Demographic, family health discussions, physical/emotional health importance, and preventive care barriers were gathered from adolescents and parents. RESULTS: The majority of the sample (500 adolescents and 504 parents in different families) reported a primary care visit within 12 months (parents = 78.7%; adolescents = 66.9%). Adolescent participants identified more barriers than parents (parents = 0.69; adolescents = 1.42). Adolescent who reported having discussions with parents about health (aOR 1.57, 95% CI 1.26-1.98) and seeing a subspecialist provider (aOR 3.72, CI 1.21-11.47) were more likely to report preventive visits. Barriers for parents and adolescents include the belief that an appointment is only needed when a child is sick (parent aOR 0.21, CI 0.08-0.61; adolescent aOR 0.29, CI 0.17-0.51) and family cannot afford cost (parent aOR 0.34, CI 0.15-0.81; adolescent aOR 0.50, CI 0.26-0.97). Barriers for parents include the child sees a specialist (aOR 0.26, CI 0.08-0.88) and their child does not need a checkup (aOR 0.12, CI 0.05-0.34). Lastly, a barrier for adolescents was parents never schedule preventive visits (aOR 0.31, CI 0.17-0.58). CONCLUSIONS: The Affordable Care Act has the potential to limit preventive care barriers. The results of the current study find there are parental and adolescent issues regarding preventive services that should be addressed. PMID- 26681477 TI - Treatment Options for Type 2 Diabetes in Youth Remain Limited. PMID- 26681478 TI - Tunable Optical Nanoantennas Incorporating Bowtie Nanoantenna Arrays with Stimuli Responsive Polymer. AB - We report on a temperature-responsive tunable plasmonic device that incorporates coupled bowtie nanoantenna arrays (BNAs) with a submicron-thick, thermosensitive hydrogel coating. The coupled plasmonic nanoparticles provide an intrinsically higher field enhancement than conventional individual nanoparticles. The favorable scaling of plasmonic dimers at the nanometer scale and ionic diffusion at the submicron scale is leveraged to achieve strong optical resonance and rapid hydrogel response, respectively. We demonstrate that the hydrogel-coated BNAs are able to sense environmental temperature variations. The phase transition of hydrogel leads to 16.2 nm of resonant wavelength shift for the hydrogel-coated BNAs, whereas only 3 nm for the uncoated counterpart. The response time of the device to temperature variations is only 250 ms, due to the small hydrogel thickness at the submicron scale. The demonstration of the ability of the device to tune its optical resonance in response to an environmental stimulus (here, temperature) suggests a possibility of making many other tunable plasmonic devices through the incorporation of coupled plasmonic nanostructures and various environmental-responsive hydrogels. PMID- 26681479 TI - The complete mitochondrial genome of the Azuma emmnion. AB - The complete mitochondrial genome of the Azuma emmnion has been determined. The total length of a complete nucleotide sequence of the mitochondria is 16 522 bp, which contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and one D-loop region. Its nucleotide sequence and composition of A. emmnion mitochondrion was similar to most other vertebrates. Nucleotide base composition of mitochondrial genome was the following: 25.58% for A, 18.22% for G, 27.67% for C, 28.53% for T. The phylogenetic analysis result, which based on the complete mitogenomes of of A. emmnion and other 11 fish species, indicated that A. emmnion and Pholis crassispina clustered into one branch. PMID- 26681480 TI - Cognitive schemas as longitudinal predictors of self-reported adolescent depressive symptoms and resilience. AB - Given that depression risk intensifies in adolescence, examining associates of depressive symptoms during the shift from childhood to adolescence is important for expanding knowledge about the etiology of depression symptoms and disorder. A longitudinal youth report was employed to examine the trajectory of both the content and structure of positive and negative schemas in adolescence and also whether these schemas could prospectively predict depressive symptoms and youth reported resilience. One hundred and ninety-eight participants (aged 9 to 14) were recruited from four schools to complete measures of youth depressive symptoms, resilience, and schema content and structure. Those who consented to a follow-up study completed the same measures online (50 participants completed). Negative and positive schema content and structure were related over time. After controlling depressive symptoms/resilience at Time 1, negative schema content was the only significant predictor (trend level) of depressive symptoms and resilience at Time 2. Implications for cognitive theories and clinical practice are discussed. PMID- 26681481 TI - Development of the ReaxFFCBN reactive force field for the improved design of liquid CBN hydrogen storage materials. AB - Liquid CBN (carbon-boron-nitrogen) hydrogen-storage materials such as 3-methyl 1,2-BN-cyclopentane have the advantage of being easily accessible for use in current liquid-fuel infrastructure. To develop practical liquid CBN hydrogen storage materials, it is of great importance to understand the reaction pathways of hydrogenation/dehydrogenation in the liquid phase, which are difficult to discover by experimental methods. Herein, we developed a reactive force field (ReaxFFCBN) from quantum mechanical (QM) calculations based on density functional theory for the storage of hydrogen in BN-substituted cyclic hydrocarbon materials. The developed ReaxFFCBN provides similar dehydrogenation pathways and energetics to those predicted by QM calculations. Moreover, molecular dynamics (MD) simulations with the developed ReaxFFCBN can predict the stability and dehydrogenation behavior of various liquid CBN hydrogen-storage materials. Our simulations reveal that a unimolecular dehydrogenation mechanism is preferred in liquid CBN hydrogen-storage materials. However, as the temperature in the simulation increases, the contribution of a bimolecular dehydrogenation mechanism also increases. Moreover, our ReaxFF MD simulations show that in terms of thermal stability and dehydrogenation kinetics, liquid CBN materials with a hexagonal structure are more suitable materials than those with a pentagonal structure. We expect that the developed ReaxFFCBN could be a useful protocol in developing novel liquid CBN hydrogen-storage materials. PMID- 26681482 TI - Nuclear Spin Conversion in CH4: A Multichannel Relaxation Mechanism. AB - Experiments on nuclear spin interconversion of ortho, para, and meta nuclear spin isomers of the methane molecule have been undertaken in gas phase and cryomatrices. Only the latter environment has led to the observation of the nuclear spin conversion. In this study, a quantitative explanation is given for the first time by considering the coupling of three relaxation paths: meta <=> para, meta <=> ortho, and ortho <=> para. The global evolution of the three populations of spin isomers is thus described by two characteristic times, which have been calculated using the best values of the energy levels for the vibrational ground state, of the intramolecular magnetic interactions, and of the collisional relaxation rates, and for different pressure and temperature conditions. Such calculations also provide an indication for the proper choice of reliable scenarios for experimental separation of the spin isomers of methane. PMID- 26681483 TI - Characterizing informative sequence descriptors and predicting binding affinities of heterodimeric protein complexes. AB - BACKGROUND: Protein-protein interactions (PPIs) are involved in various biological processes, and underlying mechanism of the interactions plays a crucial role in therapeutics and protein engineering. Most machine learning approaches have been developed for predicting the binding affinity of protein protein complexes based on structure and functional information. This work aims to predict the binding affinity of heterodimeric protein complexes from sequences only. RESULTS: This work proposes a support vector machine (SVM) based binding affinity classifier, called SVM-BAC, to classify heterodimeric protein complexes based on the prediction of their binding affinity. SVM-BAC identified 14 of 580 sequence descriptors (physicochemical, energetic and conformational properties of the 20 amino acids) to classify 216 heterodimeric protein complexes into low and high binding affinity. SVM-BAC yielded the training accuracy, sensitivity, specificity, AUC and test accuracy of 85.80%, 0.89, 0.83, 0.86 and 83.33%, respectively, better than existing machine learning algorithms. The 14 features and support vector regression were further used to estimate the binding affinities (Pkd) of 200 heterodimeric protein complexes. Prediction performance of a Jackknife test was the correlation coefficient of 0.34 and mean absolute error of 1.4. We further analyze three informative physicochemical properties according to their contribution to prediction performance. Results reveal that the following properties are effective in predicting the binding affinity of heterodimeric protein complexes: apparent partition energy based on buried molar fractions, relations between chemical structure and biological activity in principal component analysis IV, and normalized frequency of beta turn. CONCLUSIONS: The proposed sequence-based prediction method SVM-BAC uses an optimal feature selection method to identify 14 informative features to classify and predict binding affinity of heterodimeric protein complexes. The characterization analysis revealed that the average numbers of beta turns and hydrogen bonds at protein-protein interfaces in high binding affinity complexes are more than those in low binding affinity complexes. PMID- 26681484 TI - Essential ultrasound techniques of the pediatric airway. AB - Ultrasound of the airways is a technique which has been described in a number of recent articles and reviews highlighting the diagnostic possibilities and simple methodology. However, there is a paucity of information focusing specifically on such methods in children where equipment, technique, and challenges are different. This review article gives a general overview of the equipment considerations, scanning protocols, and clinical applications in children. PMID- 26681485 TI - Amount May Beat Timing: Gluten Intake and Risk of Childhood Celiac Disease. PMID- 26681486 TI - Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis. AB - BACKGROUND & AIMS: Mucosal healing is an independent predictor of sustained clinical remission in patients with ulcerative colitis (UC) treated with infliximab. We investigated whether infliximab concentrations during induction therapy are associated with short-term mucosal healing (STMH) in patients with UC. METHODS: We performed a retrospective, single-center analysis of data collected from a tertiary referral center from 101 patients with UC who received scheduled induction therapy with infliximab at weeks 0, 2, and 6 and had an endoscopic evaluation at baseline and after induction therapy. STMH was defined as Mayo endoscopic sub-score <=1, assessed at weeks 10-14, with baseline sub score >=2. Infliximab concentrations were evaluated in serum samples collected at weeks 0, 2, 6, and 14 of infliximab therapy by using an enzyme-linked immunosorbent assay we developed. RESULTS: Fifty-four patients (53.4%) achieved STMH. Patients with STMH had a higher median infliximab concentration at weeks 2, 6, and 14 than patients without STMH. A receiver operating characteristic (ROC) analysis identified infliximab concentration thresholds of 28.3 (area under the ROC curve [AUROC], 0.638), 15 (AUROC, 0.688), and 2.1 MUg/mL (AUROC, 0.781) that associated with STMH at weeks 2, 6, and 14, respectively. Multiple logistic regression analysis identified infliximab concentration >=15 at week 6 (P = .025; odds ratio, 4.6; 95% confidence interval, 1.2-17.1) and >=2.1 MUg/mL at week 14 (P = .004; odds ratio, 5.6; 95% confidence interval, 1.7-18) as independent factors associated with STMH. CONCLUSIONS: In an analysis of data from real-life clinical practice, we associated infliximab concentrations during the induction therapy with STMH in patients with UC. PMID- 26681487 TI - Providing Hospitalized Patients With an Educational Booklet Increases the Quality of Colonoscopy Bowel Preparation. AB - BACKGROUND & AIMS: Inadequate bowel preparation is a problem frequently encountered by gastroenterologists who perform colonoscopies on hospitalized patients. A method is needed to increase the quality of bowel preparation in inpatients. An educational booklet has been shown to increase the overall quality of bowel preparation for outpatients. We performed a prospective study to evaluate the effects of an educational booklet on the quality of bowel preparation in a group of hospitalized patients. METHODS: We performed a randomized, single-blind, controlled trial of all inpatients at a tertiary care medical center scheduled for inpatient colonoscopy from October 2013 through March 2014. They were randomly assigned to groups that were (n = 45) or were not (controls, n = 40) given the booklet before bowel preparation the evening before their colonoscopy. All patients received a standard bowel preparation (clear liquid diet the day before the procedure, followed by split-dose GoLYTELY). At the colonoscopy, the Boston Bowel preparation scale (BBPS) was used to assess bowel preparation. The primary outcome measure was adequate bowel preparation (a total BBPS score >=6 with all segment scores >=2). Secondary outcomes assessed included total BBPS score, BBPS segment score, and a total BBPS score of 0. RESULTS: There were no differences between the groups in age, race, sex, body mass index, history of colonoscopy, history of polyps, or time of colonoscopy. Twenty-eight patients who received the booklet (62%) and 14 who did not (35%) had an adequate bowel preparation (P = .012). The number needed to treat to attain adequate bowel preparation was 4. After adjusting for age and history of prior colonoscopies, the odds of achieving an adequate bowel preparation and a higher total BBPS score after receipt of the booklet were 3.14 (95% confidence interval, 1.29-7.83) and 2.27 (95% confidence interval, 1.05-4.88), respectively. Three patients in the booklet group and 9 in the no-booklet group had a BBPS score of 0 (P = .036). The mean BBPS segment score was greater for the booklet group than the no-booklet group (right colon, P = .097; transverse colon, P = .023; left colon, P = .045). CONCLUSIONS: In a randomized controlled trial, we found that providing hospitalized patients with an educational booklet on colonoscopy preparation increases the odds of a quality bowel preparation more than 2-fold. PMID- 26681489 TI - Antidepressants for Functional Dyspepsia: New Indications for Old Therapies? PMID- 26681488 TI - Coffee or Tea, Hot or Cold, Are Not Associated With Risk of Barrett's Esophagus. AB - Epidemiologic data regarding coffee and tea consumption and risk of esophageal inflammation, Barrett's esophagus (BE), and adenocarcinoma are sparse and inconclusive. This study examined the association between consumption of tea or coffee with risk of BE. We conducted a cross-sectional study among US veterans, comparing 310 patients with histologically confirmed BE with 1728 individuals with no endoscopic or histopathologic features of BE (controls). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. In univariate models, we found a statistically significant association between risk of BE and consumption of coffee (OR, 1.41; 95% CI, 1.06 1.87) or tea (OR, 1.34; 95% CI, 1.05-1.71). However, in multivariate analysis, in which models were adjusted for confounders including sex and race, we found no association between risk of BE and consumption of coffee (adjusted OR, 1.04; 95% CI, 0.76-1.42) or tea (adjusted OR, 1.11; 95% CI, 0.85-1.44). These data do not support an association between consumption of coffee or tea and the risk of BE. It is unlikely that avoidance of coffee or tea will protect against BE. PMID- 26681490 TI - Spatiotemporal mapping of interictal epileptiform discharges in human absence epilepsy: A MEG study. AB - PURPOSE: Although absence epilepsy is considered to be a prototypic type of generalized epilepsy, it is still under debate whether generalized 3 Hz spike-and wave discharges (SWDs) might have a cortical focal origin. Here it is investigated whether focal interictal epileptiform discharges (IEDs), which typically occur in the electro- (EEG) and magnetoencephalogram (MEG) in case of focal epilepsy, are present in the MEG of children with absence epilepsy. Next, the location of the sources of the IEDs is established, and it is investigated whether the location is concordant to the earlier established focal cortical regions involved in the generalized SWDs of these children. METHODS: Whole head MEG recordings of seven children with absence epilepsy were reviewed with respect to the presence of IEDs (spikes and sharp waves). These IEDs were grouped into distinct clusters, in which each contribution to a cluster yields a comparable magnetic field distribution. Source localization was then performed onto the average signal of each cluster using an equivalent current dipole model and a realistic head model of the cortical surface. RESULTS: IEDs were detected in 6 out of 7 patients. Source reconstruction indicated most often frontal, central or parietal origins of the IED in either the left and or right hemisphere. Spatiotemporal assessment of the IEDs indicated a stable location of the averages of these discharges, indicating a single underlying cortical source. DISCUSSION: The outcome of this pilot study shows that MEG is well suited for the detection of IEDs and suggests that their estimated sources coincide rather well with the cortical regions involved during the spikes of the SWDs. It is discussed whether the presence of IEDs, classically seen as a marker of focal epilepsies, indicate that absence epilepsy should be considered as a focal type of epilepsy, in which changes in the network are evolving rapidly. PMID- 26681491 TI - Influence of author's affiliation and funding sources on the results of cohort studies on occupational cancer. AB - BACKGROUND: Reliability and credibility of research conducted by industry have been questioned, including in the field of occupational health. METHODS: Cohort studies on occupational cancer published between 2000 and 2010 were compared according to their results, their conclusions, their funding, and the affiliation of their authors. RESULTS: Overall, 510 articles were included. Studies published by authors with public affiliation or funded by public grants concluded that their study showed an excess of cancer more frequently (P = 0.01) than studies published by authors with private affiliation or funded by private grants (88% [95%CI = 85-91] vs. 73% [95%CI = 56-88] and 92% [95%CI = 86-97] vs. 71% [95%CI = 57-84], respectively). Discrepancies between statistical results and conclusion occurred more frequently in articles written by authors from the private sector than from the public sector (42% [IC95% = 26-60] vs. 23% [IC95% = 18-26], P = 0.02). CONCLUSIONS: Industry affiliations of authors or industry support of studies are associated with the results of published studies on occupational cancer. The underlying mechanisms warrant further investigation. PMID- 26681492 TI - Changes in the composition of ichthyoplankton assemblage and plastic debris in mangrove creeks relative to moon phases. AB - Lunar influence on the distribution of fish larvae, zooplankton and plastic debris in mangrove creeks of the Goiana Estuary, Brazil, was studied over a lunar cycle. Cetengraulis edentulus, Anchovia clupeoides and Rhinosardinia bahiensis were the most abundant fish larvae (56.6%), independent of the moon phase. The full moon had a positive influence on the abundance of Gobionellus oceanicus, Cynoscion acoupa and Atherinella brasiliensis, and the new moon on Ulaema lefroyi. The full and new moons also influenced the number of zoeae and megalopae of Ucides cordatus, protozoeae and larvae of caridean shrimps, and the number of hard and soft plastic debris, both <5 and >5 mm. Micro and macroplastics were present in samples from all 12 creeks studied, at densities similar to the third most abundant taxon, R. bahiensis. Cetengraulis edentulus and R. bahiensis showed a strong positive correlation with the last quarter moon, when there was less zooplankton available in the creeks and higher abundance of microplastic threads. Anchovia clupeoides, Diapterus rhombeus, U. lefroyi and hard microplastics were positively associated with different moon phases, when calanoid copepods, Caridean larvae and zoeae of U. cordatus were highly available in the creeks. Cynoscion acoupa, G. oceanicus and A. brasiliensis were strongly associated with the full moon, when protozoeae of caridean shrimps and megalopae of U. cordatus were also highly available, as were hard and soft macroplastics, paint chips (<5 mm) and soft microplastics. The results reinforce the role of mangrove creeks as nursery habitats. The moon phases influenced the distribution of fish larvae species, zooplankton and plastic debris by changing their compositions and abundances in the mangrove creeks of the Goiana Estuary when under the influence of different tidal current regimes. PMID- 26681493 TI - Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population. AB - Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case-control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24-1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16-2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49-3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31-2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations. PMID- 26681494 TI - Crim1 regulates integrin signaling in murine lens development. AB - The developing lens is a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or interactions. Cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1(glcr11), which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1(null) and Crim1(cko), we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active beta1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated LE cell adhesion during lens development. PMID- 26681498 TI - Improving the Advance Directive Request and Retrieval Process in Critical Access Hospitals: Honoring the Patient's Wishes. AB - The Patient Self-Determination Act was created to enhance awareness and use of advance directives. Several states also have created registries where the advance directives can be easily retrieved when needed. Quick retrieval is especially important in critical access hospitals where patients are often transferred to other facilities. This article describes an innovative project designed to improve the advance directives request and retrieval process on admission to a critical access hospital. PMID- 26681496 TI - Cannabinoid Transmission in the Hippocampus Activates Nucleus Accumbens Neurons and Modulates Reward and Aversion-Related Emotional Salience. AB - BACKGROUND: Cannabinoid receptor transmission strongly influences emotional processing, and disturbances in cannabinoid signaling are associated with various neuropsychiatric disorders. The mammalian ventral hippocampus (vHipp) is a critical neural region controlling mesolimbic activity via glutamatergic projections to the nucleus accumbens. Furthermore, vHipp abnormalities are linked to schizophrenia-related psychopathology. Nevertheless, the mechanisms by which intra-vHipp cannabinoid signaling may modulate mesolimbic activity states and emotional processing are not currently understood. METHODS: Using an integrative combination of in vivo electrophysiological recordings and behavioral pharmacologic assays in rats, we tested whether activation of cannabinoid type 1 receptors (CB1R) in the vHipp may modulate neuronal activity in the shell subregion of the nucleus accumbens (NASh). We next examined how vHipp CB1R signaling may control the salience of rewarding or aversive emotional memory formation and social interaction/recognition behaviors via intra-NASh glutamatergic transmission. RESULTS: We demonstrate for the first time that vHipp CB1R transmission can potently modulate NASh neuronal activity and can differentially control the formation of context-dependent and context-independent forms of rewarding or aversion-related emotional associative memories. In addition, we found that activation of vHipp CB1R transmission strongly disrupts normal social behavior and cognition. Finally, we report that these behavioral effects are dependent upon intra-NASh alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/N-methyl-D-aspartate receptor transmission. CONCLUSIONS: Together, these findings demonstrate a critical role for hippocampal cannabinoid signaling in the modulation of mesolimbic neuronal activity states and suggest that dysregulation of CB1R transmission in the vHipp->NASh circuit may underlie hippocampal-mediated affective and social behavioral disturbances present in neuropsychiatric disorders. PMID- 26681495 TI - Genetic Markers of Human Evolution Are Enriched in Schizophrenia. AB - BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities. METHODS: We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score. RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 * 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development. CONCLUSIONS: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human. PMID- 26681499 TI - Engaging Direct Care Providers in Improving Infection Prevention and Control Practices Using Participatory Visual Methods. AB - The purpose of this quality improvement project was to determine the feasibility of using provider-led participatory visual methods to scrutinize 4 hospital units' infection prevention and control practices. Methods included provider-led photo walkabouts, photo elicitation sessions, and postimprovement photo walkabouts. Nurses readily engaged in using the methods to examine and improve their units' practices and reorganize their work environment. PMID- 26681500 TI - The factors causing bad sleep. PMID- 26681501 TI - The risk of new onset depression in association with influenza--A population based observational study. AB - IMPORTANCE: Case-reports provided evidence that influenza infections, particularly severe episodes, may exert neuronal damage in the CNS and thereby increase the risk of depression. OBJECTIVE: It was the aim of this study to analyse the association between influenza infections and the risk of developing incident depression. DESIGN: We conducted a case-control analysis between 2000 and 2013 using the large UK-based primary care database Clinical Practice Research Datalink (CPRD). SETTING: This database contains anonymous longitudinal data from primary care. At present, it contains over 100 million person-years of data from some 10 million active patients. PARTICIPANTS: We encompassed 103307 patients below the age of 80 years with an incident major depression diagnosis between 2000 and 2013, and matched each case to one control patient on age, sex, general practice, number of medical encounters, and years of history in the CPRD prior to the index date. EXPOSURE: Major depression diagnosis was identified by READ-codes based on ICD-10 codes (F32), with a minimum of three prescriptions for antidepressant drugs recorded after the diagnosis. MAIN OUTCOME: We calculated relative risk estimates of developing depression in association with previous influenza infections, stratified by the number, timing and severity of such events, and we adjusted for a variety of comorbidities, smoking status, alcohol intake, body mass index, use of oral corticosteroids, and benzodiazepines. RESULTS: Patients with a previous influenza infection had an increased risk of developing depression (OR 1.30, 95%CI 1.25-1.34) compared to patients with no history of influenza infections. A recent influenza infection recorded within 30 180 days prior to the index date yielded an adjusted 1.57 (95%CI 1.36-1.81), and an increasing number of previous influenza infections was associated with increasing odds ratios (? 3 recorded influenza infections, adjusted OR 1.48, 95%CI 1.22-1.81). CONCLUSION: This study suggests that influenza infections are associated with a moderately increased risk of developing depression. PMID- 26681502 TI - Palladium-Catalyzed Enantioselective Domino Heck/Intermolecular C-H Bond Functionalization: Development and Application to the Synthesis of (+) Esermethole. AB - Intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by intermolecular trapping of the resulting sigma-C(sp(3))-Pd complex by azoles afforded 3,3-disubstituted oxindoles in good yields with excellent enantioselectivities. Two C-C bonds were created with concurrent formation of an all-carbon quaternary stereocenter. Oxadiazole substituted oxindoles were subsequently converted to pyrroloindolines by an unprecedented reductive cyclization protocol. The utility of this chemistry was illustrated by an enantioselective synthesis of (+)-esermethole. PMID- 26681503 TI - Prevalence of methicillin-resistant Staphylococcus aureus in Canadian commercial pork processing plants. AB - AIMS: This study investigated the prevalence of Methicillin-resistant Staphylococcus aureus (MRSA), their spa-types, and antimicrobial resistance profiles at various steps during commercial pork production from three plants designated as A, B and C. METHODS AND RESULTS: Over a period of 1 year 2640 samples from three commercial pork plants were obtained on a rotating basis. Sample sources were: nasal swabs after bleeding (NSAB), nasal swab after scalding (NSASs, plant C) or skinning (NSASk, plants A, B), carcass swabs after pasteurization (CSAP, plant C) or washing (CSAW, plants A, B) and retail pork (RP). Overall MRSA prevalence at each sampling point in the pork plants after adjusting for clustering was: 61.93, 28.38 7.58 and 1.21% for NSAB, NSASc/Sk, CSAP/CSAW and RP respectively. The majority of MRSA isolates from the three pork plants belonged to livestock-associated MRSA spa-types t034 and t011 (3.8%; ST398). The mainly human spa-type t002 (15%) was also recovered. All MRSA isolates were resistant to beta-lactam and tetracycline antibiotics. Overall resistance to tigecycline was found in about 10% of MRSA isolates while <3% isolates were resistant to daptomycin, gentamicin, quinupristin/dalfopristin and trimethoprim/sulfamethoxazole. CONCLUSION: A higher prevalence of MRSA in the nasal cavity of incoming pigs was observed at all three plants, but a notable reduction in MRSA along the pork processing steps occurred. SIGNIFICANCE AND IMPACT OF THE STUDY: The highest prevalence of MRSA was found in the nasal cavity of incoming pigs in three commercial pig slaughter and pork processing plants. A reduction in MRSA prevalence occurred along the processing chain, and pork products from these plants showed significantly lower MRSA than the initial steps of slaughter and processing, suggesting a reduction in MRSA during the slaughter process with minimal cross-contamination. PMID- 26681504 TI - Hemoptysis and Progressive Dyspnea in a 67-Year-Old Woman with History of Renal Transplantation. PMID- 26681505 TI - Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. AB - BACKGROUND: Risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluations from patients at highly specialized centers. AIM: To evaluate risk markers for appropriate implantable cardioverter defibrillator (ICD) therapy in an unselected, nationwide cohort of HCM. METHODS: Patients with an ICD due to HCM were identified from the Swedish ICD Registry since its start in 1995, merged with Patient Register data, and medical records were retrieved. Risk markers for ventricular arrhythmias leading to appropriate ICD therapy were analyzed using Cox proportional hazard ratio (HR). RESULTS: Of 321 patients (70.1% males), at least one appropriate therapy occurred in 77 (24.0%) during a mean follow-up of 5.4 years (5.3% per year; primary prevention 4.5%, secondary prevention 7.0%). Cumulative incidences at 1 year, 3 years, and 5 years were 8.1%, 15.3%, and 21.3%, respectively. Cardioversion effectively restored rhythm in 52% of the first episode and antitachycardia pacing was sufficient in the remaining. For the whole cohort, ejection fraction (EF) <50% (HR 2.63; P < 0.001) was associated with appropriate ICD therapy. In primary prevention, patients with established risk markers experienced appropriate therapy; atrial fibrillation (AF; HR 2.54; P = 0.010), EF < 50% (HR 2.78; P = 0.004), and nonsustained ventricular tachycardia (HR 1.80; P = 0.109) had the highest HR, and wall thickness >= 30 mm, syncope, exercise blood pressure response, or family history of SCD had weaker associations. CONCLUSION: ICD therapy successfully terminates ventricular arrhythmias in HCM. In addition to conventional risk markers, a history of AF or EF < 50% may be considered in risk stratification. PMID- 26681506 TI - Anatomical study of the musculus deltoideus and musculus flexor carpi ulnaris in 3 species of wild birds. AB - Given the limited information regarding the anatomy of the thoracic limb in European avian species, we decided to investigate the related muscles in the grey heron (Ardea cinerea), in the eurasian buzzard (Buteo buteo), and in the common kestrel (Falco tinnunculus). Therefore we performed a stratigraphic dissection of the wing in 3 subjects. The pars major and minor of the musculus deltoideus, despite being roughly in line with those reported by other authors in other species, displayed unique features. Concerning the pars propatagialis of the musculus deltoideus, from what was observed in the grey heron, we believe this structure can contribute to maintain the propatagial tension. In this way vibrations of this structure, which could cause diminished lift, are avoided. Moreover the peculiarity evidenced in the distal insertion of the common kestrel could influence the control of the pronation-supination of the wing during hovering. With respect to the musculus flexor carpi ulnaris, we believe the presence of a sesamoid-like structure at the base tendon, found in the grey heron and in the eurasian buzzard, may help complete the articular surfaces of the elbow. This study shows interesting data on species not previously examined and provides a possible functional correlation between the peculiarity observed and the kind of flight of each species. PMID- 26681507 TI - Pelvic limb alignment in small breed dogs: a comparison between affected and free subjects from medial patellar luxation. AB - Small breed dogs are 12 times more likely to develop medial patellar luxation (MPL) than large breed dogs and breed predisposition has been reported. Many surgical techniques are available for correction of patellar luxation in dogs. However, recent studies reported an 8% incidence of reluxation when traditional techniques are used. The relatively high frequency of major complications and patellar reluxation may be partially caused by inadequate appreciation of the underlying skeletal deformity and subsequent incorrect selection and application of traditional techniques. The aims of this study were to report the normal values of the anatomic and mechanical joint angles of the femur and tibia in small breed dogs and to compare these data to a population of small breed dogs affected by different degrees of MPL. Normal values of the anatomic and mechanical angles of the femur are similar to the ones reported in literature in Pomeranian dogs. Normal values of the anatomic and mechanical angles of the tibia have been described for the first time. Significant differences were found between normal population and dogs affected by grade 4 MPL in relation to anatomical Lateral Distal Femoral Angle (aLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), and mechanical Caudal Proximal Tibial Angle (mCaPTA). PMID- 26681508 TI - Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity. AB - Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones (NPDOs), a new type of N heterocycle-fused o-quinones, have been synthesized. They have been found to be efficient electron-accepting substrates of NADPH-dependent single-electron transferring P-450R and two-electron transferring NQO1, generating reactive oxygen species (ROS) with a concomitant decrease in NADPH, which is consistent with redox-cycling. The reactivity of NPDOs toward P-450R (in terms of kcat/Km) varied in the range of 10(6)-10(7)M(-1)s(-1), while their reduction by NQO1 proceeded much faster, approaching the diffusion control limit (kcat/Km~10(8) 10(9)M(-1)s(-1)). NPDOs exhibited relatively high cytotoxic activity against human lung carcinoma (A-549) and breast tumor (MCF-7) cell lines (LC50=0.1 8.3MUM), while promyelocytic leukemia cells (HL-60) were less sensitive to NPDOs (LC50?10MUM). 3-Nitro-substituted NPDO (11) revealed the highest potency against both A-549 and MCF-7 cell lines, with LC50 of 0.12+/-0.03MUM and 0.28+/-0.08MUM, respectively. Dicoumarol partly suppressed the activity of the compounds against A-594 and MCF-7 cell lines, suggesting that their cytotoxic action might be partially influenced by NQO1-mediated bioreductive activation. PMID- 26681509 TI - Synthesis, in vitro antibacterial activities of a series of 3-N-substituted canthin-6-ones. AB - An improved synthetic route of canthin-6-one was accomplished. To further enhance the antibacterial potency and improve water solubility, a series of 3-N-alkylated and 3-N-benzylated canthin-6-ones were designed and synthesized, and their in vitro antibacterial activities were evaluated. A clear structure-activity relationship with peak minimal inhibitory concentration (MIC) values of 0.98 (MUg.mL(-)(1)) was investigated. Particularly, compounds 6i-r and 6t were found to be the most potent compounds with minimal inhibitory concentration (MIC) values lower than 1.95 (MUg.mL(-)(1)) against Staphylococcus aureus. PMID- 26681510 TI - Syntheses and anti-inflammatory activity of azamollugin derivatives. AB - Oxomollugin (2) is a degradation product of mollugin (1) and a potent inhibitor of NO-production including nuclear factor kappa B signals. In our endeavor to develop a potent anti-inflammatory compound, we synthesized several aza derivatives of oxomollugin (2) and evaluated their NO-production inhibitory activity. Azamollugin (3) showed a potent inhibitory activity, and its activity (IC50 0.34MUM) was proved to be more potent than that of oxomollugin (2, IC50 1.3MUM). PMID- 26681511 TI - Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors. AB - A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency. PMID- 26681512 TI - Improved synthesis of MC4-PPEA and the biological evaluation of its hydroxymethyl derivative. AB - Nicotinamide phosphoribosyltransferase (Nampt) is an intriguing target for the treatment of many diseases, including cancer. Previously, our group demonstrated that carborane clusters may be used to increase the potency of small molecule inhibitors of Nampt over other, similarly sized organic moieties. Herein, we report a greatly improved, gram-scale synthesis of our most potent agent: 1-(4' (trans-3"-(3'''-pyridyl) acrylamide)butyl)-1,7-dicarba-closo-dodecaborane (MC4 PPEA). Additionally, the carborane moiety of the molecule has been modified with a hydroxymethyl functional group to allow for its covalent attachment to targeted prodrugs, the synthesis of which are underway. Using cell viability assays, we demonstrate that this new derivative exhibits low, to mid-nanomolar potencies against human breast cancer cell lines in vitro. PMID- 26681514 TI - Monoorganoantimony(v) phosphonates and phosphoselininates. AB - Molecular oxo-hydroxo clusters have been synthesized by reactions of arylstibonic acids with organophosphonic acid and phenylseleninic acid. Single crystal X-ray structural elucidation revealed the formation of [(p-i-PrC6H4Sb)4(OH)4(t-BuPO3)6] (1), [(p-t-BuC6H4Sb)4(O)2(PhPO3)4(PhPO3H)4] (2), [(p-i PrC6H4Sb)4(O)3(OH)(PhSeO2)2(t-BuPO3)4(t-BuPO3H2)2] (3), [(p MeC6H4Sb)4(O)3(OH)(PhSeO2)2(t-BuPO3)4(t-BuPO3H2)2] (4) and [(p-t-BuC6H4Sb)2(O) (PhSeO2)2(t-BuPO3H)4] (5) respectively. Mass spectral studies reveal that the clusters maintain their structural integrity in solution as well. Solution NMR studies ((1)H, (31)P and (77)Se) show spectral patterns which correlate well with the observed solid state structures of 1-5. PMID- 26681513 TI - Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities. AB - The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5 c]pyrimidine-2-yl) acetamidoximes 2a-e has been accomplished by reaction of 2 acetonitrile derivatives 1a-e with hydroxylamine. Cyclocondensation reaction of precursors 2a-e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a-e, 4a-e, and 5a-e, respectively. On the other hand, the reaction of precursors 2a-e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a-e which evolve under reflux of toluene to the new oxadiazoles 7a-e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC50 = 4.0 MUM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 MUM, respectively) while 2e is highly selective against OVCAR-3 (IC50 = 10 MUM). PMID- 26681515 TI - MicroRNA Maturation and MicroRNA Target Gene Expression Regulation Are Severely Disrupted in Soybean dicer-like1 Double Mutants. AB - Small nonprotein-coding microRNAs (miRNAs) are present in most eukaryotes and are central effectors of RNA silencing-mediated mechanisms for gene expression regulation. In plants, DICER-LIKE1 (DCL1) is the founding member of a highly conserved family of RNase III-like endonucleases that function as core machinery proteins to process hairpin-like precursor transcripts into mature miRNAs, small regulatory RNAs, 21-22 nucleotides in length. Zinc finger nucleases (ZFNs) were used to generate single and double-mutants of putative soybean DCL1 homologs, DCL1a and DCL1b, to confirm their functional role(s) in the soybean miRNA pathway. Neither DCL1 single mutant, dcl1a or dcl1b plants, exhibited a pronounced morphological or molecular phenotype. However, the dcl1a/dcl1b double mutant expressed a strong morphological phenotype, characterized by reduced seed size and aborted seedling development, in addition to defective miRNA precursor transcript processing efficiency and deregulated miRNA target gene expression. Together, these findings indicate that the two soybean DCL1 paralogs, DCL1a and DCL1b, largely play functionally redundant roles in the miRNA pathway and are essential for normal plant development. PMID- 26681516 TI - Genome-Wide Analysis of the TORC1 and Osmotic Stress Signaling Network in Saccharomyces cerevisiae. AB - The Target of Rapamycin kinase Complex I (TORC1) is a master regulator of cell growth and metabolism in eukaryotes. Studies in yeast and human cells have shown that nitrogen/amino acid starvation signals act through Npr2/Npr3 and the small GTPases Gtr1/Gtr2 (Rags in humans) to inhibit TORC1. However, it is unclear how other stress and starvation stimuli inhibit TORC1, and/or act in parallel with the TORC1 pathway, to control cell growth. To help answer these questions, we developed a novel automated pipeline and used it to measure the expression of a TORC1-dependent ribosome biogenesis gene (NSR1) during osmotic stress in 4700 Saccharomyces cerevisiae strains from the yeast knock-out collection. This led to the identification of 440 strains with significant and reproducible defects in NSR1 repression. The cell growth control and stress response proteins deleted in these strains form a highly connected network, including 56 proteins involved in vesicle trafficking and vacuolar function; 53 proteins that act downstream of TORC1 according to a rapamycin assay--including components of the HDAC Rpd3L, Elongator, and the INO80, CAF-1 and SWI/SNF chromatin remodeling complexes; over 100 proteins involved in signaling and metabolism; and 17 proteins that directly interact with TORC1. These data provide an important resource for labs studying cell growth control and stress signaling, and demonstrate the utility of our new, and easily adaptable, method for mapping gene regulatory networks. PMID- 26681517 TI - An Amphiphysin-Like Domain in Fus2p Is Required for Rvs161p Interaction and Cortical Localization. AB - Cell-cell fusion fulfils essential roles in fertilization, development and tissue repair. In the budding yeast, Saccharomyces cerevisiae, fusion between two haploid cells of opposite mating type generates the diploid zygote. Fus2p is a pheromone-induced protein that regulates cell wall removal during mating. Fus2p shuttles from the nucleus to localize at the shmoo tip, bound to Rvs161p, an amphiphysin. However, Rvs161p independently binds a second amphiphysin, Rvs167p, playing an essential role in endocytosis. To understand the basis of the Fus2p Rvs161p interaction, we analyzed Fus2p structural domains. A previously described N-terminal domain (NTD) is necessary and sufficient to regulate nuclear/cytoplasmic trafficking of Fus2p. The Dbl homology domain (DBH) binds GTP bound Cdc42p; binding is required for cell fusion, but not localization. We identified an approximately 200 amino acid region of Fus2p that is both necessary and sufficient for Rvs161p binding. The Rvs161p binding domain (RBD) contains three predicted alpha-helices; structural modeling suggests that the RBD adopts an amphiphysin-like structure. The RBD contains a 13-amino-acid region, conserved with Rvs161p and other amphiphysins, which is essential for binding. Mutations in the RBD, predicted to affect membrane binding, abolish cell fusion without affecting Rvs161p binding. We propose that Fus2p/Rvs161p form a novel heterodimeric amphiphysin required for cell fusion. Rvs161p binding is required but not sufficient for Fus2p localization. Mutations in the C-terminal domain (CTD) of Fus2p block localization, but not Rvs161p binding, causing a significant defect in cell fusion. We conclude that the Fus2p CTD mediates an additional, Rvs161p-independent interaction at the shmoo tip. PMID- 26681518 TI - Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae. AB - Extrachromosomal circular DNA (eccDNA) derived from chromosomal Ty retrotransposons in yeast can be generated in multiple ways. Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA. Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination. By performing an in-depth investigation of sequence reads stemming from Ty eccDNAs obtained from populations of Saccharomyces cerevisiae S288c, we find that eccDNAs predominantly correspond to full-length Ty1 elements. Analyses of sequence junctions reveal no signs of NHEJ or autointegration events. We detect recombination junctions that are consistent with yeast Ty eccDNAs being generated through recombination events within the genome. This opens the possibility that retrotransposable elements could move around in the genome without an RNA intermediate directly through DNA circularization. PMID- 26681520 TI - FASTmC: A Suite of Predictive Models for Nonreference-Based Estimations of DNA Methylation. AB - We describe a suite of predictive models, coined FAST(m)C, for nonreference, cost effective exploration and comparative analysis of context-specific DNA methylation levels. Accurate estimations of true DNA methylation levels can be obtained from as few as several thousand short-reads generated from whole-genome bisulfite sequencing. These models make high-resolution time course or developmental and large diversity studies practical regardless of species, genome size, and availability of a reference genome. PMID- 26681519 TI - Back to Acid Soil Fields: The Citrate Transporter SbMATE Is a Major Asset for Sustainable Grain Yield for Sorghum Cultivated on Acid Soils. AB - Aluminum (Al) toxicity damages plant roots and limits crop production on acid soils, which comprise up to 50% of the world's arable lands. A major Al tolerance locus on chromosome 3, AltSB, controls aluminum tolerance in sorghum [Sorghum bicolor (L.) Moench] via SbMATE, an Al-activated plasma membrane transporter that mediates Al exclusion from sensitive regions in the root apex. As is the case with other known Al tolerance genes, SbMATE was cloned based on studies conducted under controlled environmental conditions, in nutrient solution. Therefore, its impact on grain yield on acid soils remains undetermined. To determine the real world impact of SbMATE, multi-trait quantitative trait loci (QTL) mapping in hydroponics, and, in the field, revealed a large-effect QTL colocalized with the Al tolerance locus AltSB, where SbMATE lies, conferring a 0.6 ton ha(-1) grain yield increase on acid soils. A second QTL for Al tolerance in hydroponics, where the positive allele was also donated by the Al tolerant parent, SC283, was found on chromosome 9, indicating the presence of distinct Al tolerance genes in the sorghum genome, or genes acting in the SbMATE pathway leading to Al-activated citrate release. There was no yield penalty for AltSB, consistent with the highly localized Al regulated SbMATE expression in the root tip, and Al-dependent transport activity. A female effect of 0.5 ton ha(-1) independently demonstrated the effectiveness of AltSB in hybrids. Al tolerance conferred by AltSB is thus an indispensable asset for sorghum production and food security on acid soils, many of which are located in developing countries. PMID- 26681521 TI - The complete chloroplast genome sequence of Cucumis sativus var. Hardwickii, the wild progenitor of cultivated cucumber. AB - The complete chloroplast genome sequence of wild cucumber (Cucumis sativus var. hardwickii) was determined and characterized in this study. The genome is of 155 277 bp in length, containing a pair of inverted repeats regions (IRs) of 25 198 bp, which are separated by a large single-copy region of 86 618 bp and a small single-copy region of 18 263 bp. The wild cucumber chloroplast genome has 130 known genes, including 85 protein-coding genes, 8 ribosomal RNA genes, and 37 tRNA genes. Among these genes, 19 comprise one or two introns. There are 11 tRNA genes present in the IR of the chloroplast genome. Phylogenomic analysis showed that C. sativus var. hardwickii forms a cluster with other Cucumis species with strong bootstrap supports and is closely related to C. sativus var. sativus. This newly sequenced chloroplast genome sequence may provide useful genetic information to explore wild cucumber germplasms for cucumber breeding programs. PMID- 26681522 TI - Dexmedetomidine, a revolution for sedation in ICU? PMID- 26681523 TI - Plasma concentrations of ropivacaine following ultrasound-guided or nerve stimulator-guided femoral nerve block: A prospective randomised study. AB - OBJECTIVE: Our aim was to establish a plasma concentration curve for ropivacaine following femoral nerve blockade and to ascertain whether the resulting plasma concentrations differ significantly depending on whether neurostimulation (NS) or ultrasound (US) guidance was used. METHODS: Sixteen male and female subjects aged 18 to 80 who were scheduled to undergo unilateral total knee replacement or anterior cruciate ligament reconstruction under general or spinal anaesthesia, and for whom a femoral nerve block was indicated for postoperative analgesia, were enrolled in this prospective, randomised study. Patients were randomised to undergo either US or NS-guidance femoral nerve blocks. All blocks were performed with 20 mL of 5mg/mL ropivacaine. Blood samples were drawn before the nerve block and 20, 30, 40, 50, 60, 70, and 80 minutes after the block. Plasma levels of ropivacaine were analysed by high performance liquid chromatography (HPLC). RESULTS: All blocks were successful and no patient showed signs or symptoms of local anaesthetic toxicity. The plasma concentration of ropivacaine peaked at 30 minutes in both arms. There was no significant difference in peak levels between US and NS-guidance (0.325+/-0.186 versus 0.356+/-0.106 MUg/mL). Cmax and tmax were very similar between groups (0.364+/-0.177 versus 0.344+/-0.127 MUg/mL, 33.75+/-15.06 versus 31.25+/-13.56 min for US and NS, respectively). CONCLUSION: Plasma concentrations of ropivacaine peak around 30 minutes after a femoral nerve block regardless of the technique used. No significant difference was found between US- and NS-guidance. PMID- 26681525 TI - Evaluating three hundred and fifty-two admissions and predictors of re-admissions for epistaxis - is it time to re-evaluate tranexamic acid in epistaxis? PMID- 26681524 TI - [The volar locking plate for extension fractures of the distal radius]. AB - OBJECTIVE: Bony healing of dislocated distal radius fractures after open reduction and internal stabilization by locking screws/pins using palmar approach. INDICATIONS: Extraarticular distal radius fractures type A2/A3, simple extra- and intraarticular fractures type C1 according to the AO classification, provided a palmar approach is possible. CONTRAINDICATIONS: Forearm soft tissue lesions/infections. As a single procedure if a volar approach not possible. SURGICAL TECHNIQUE: Palmar approach to the distal radius and fracture. Open reduction. Palmar fixation of the plate to radial shaft with single screw. After fluoroscopy, distal fragments fixed using locking screws. POSTOPERATIVE MANAGEMENT: Below-the-elbow cast for 2 weeks. Early exercise of thumb and fingers, wrist mobilization after cast removal. Complete healing after 6-8 weeks. RESULTS: Ten patients averaged 100% range of motion of the unaffected side after 43+/-21 months. No complications observed. DASH score averaged 12+/-16 points; Krimmer wrist score was excellent in 7, good in 2, and fair in one. PMID- 26681526 TI - Estrogen action: Receptors, transcripts, cell signaling, and non-coding RNAs in normal physiology and disease. PMID- 26681527 TI - Clinical and economic review of secukinumab for moderate-to-severe plaque psoriasis. AB - Secukinumab represents the first IL-17A antagonist among the available biologic therapies approved for moderate-to-severe plaque psoriasis management. Secukinumab demonstrated greater efficacy over placebo, etanercept and ustekinumab in patients that had limited benefit from non-biologic systemic therapies and phototherapy. Despite standard-of-care systemic therapies being more likely to be cost-effective at this time, a Canadian cost-utility analysis found secukinumab to display benefit in quality-of-life gains in moderate-to severe plaque psoriasis patients, and greater cost-effectiveness when compared to other biologic systemic therapies. Determination of the true economic value of secukinumab amongst the available therapies for moderate-to-severe plaque psoriasis will require continued economic evaluation. PMID- 26681528 TI - [Cheilitis: Diagnosis and treatment]. AB - The whole examination of oral cavity, other mucosae and skin is required when managing a cheilitis. Irritants (climatic, mechanical, caustic agents...) constitute the main aetiological factors of cheilitis. Allergic contact cheilitis should be investigated with a detailed anamnesis in order to search any causative agent in contact with the oral mucosae. Patch testing is required to confirm the diagnosis of delayed hypersensivity. Chronic actinic cheilitis occurs mostly in middle-aged, fair-skinned men. It is a potentially malignant condition that requires biopsies to exclude severe dysplasia or carcinoma. Angular cheilitis can occur spontaneously but is frequently related with several precipitating factors, such as systemic immune suppression, local irritation and moisture, fungal and/or bacterial infection. Cheilitis can also be seen in various systemic conditions such as lichen planus, lupus, atopic dermatitis and nutritional deficiencies. Erosive and crusty cheilitis and bullous erosive stomatitis are the main oral features of erythema multiforme and Stevens-Johnson syndrome. Granulomatous macrocheilitis (cheilitis granulomatosa) presents with intermittent or permanent lip swelling. It should be confirmed by a biopsy. It can be either isolated (Miescher macrocheilitis) or associated with various systemic conditions. PMID- 26681529 TI - Monosaccharide composition analysis of immunomodulatory polysaccharides by on line hollow fiber microextraction with high-performance liquid chromatography. AB - The monosaccharide compositions of functional polysaccharides are essential for structure elucidation and biological activity determination. A sensitive method based on on-line hollow-fiber liquid-phase microextraction with high-performance liquid chromatography has been established for the analysis of ten monosaccharide compositions (two uronic acids, two amino sugars and six neutral sugars) of the immunomodulatory polysaccharides. After derivatization, the sample was injected into the lumen of a hollow fiber immersed in butyl ether and separated by liquid chromatography. Under optimized conditions, the calibration curves were linear (r >= 0.9996) in the range of 10-2000 MUmol L(-1) . The limits of detection were in the range of 0.04-1.58 MUmol L(-1) , and the recoveries were in the range of 92.1 99.6%, which shows that the method is applicable to the analysis of the monosaccharide composition of various polysaccharides. PMID- 26681530 TI - Diagnosing ADHD in Adults: An Examination of the Discriminative Validity of Neuropsychological Tests and Diagnostic Assessment Instruments. AB - OBJECTIVE: The objective of this study is to investigate the discriminative validity of neuropsychological tests and diagnostic assessment instruments in diagnosing adult ADHD in a clinical psychiatric population. METHOD: Of 108 patients, 60 were diagnosed with ADHD. The Diagnostic Interview for ADHD in adults (DIVA 2.0) and Adult ADHD Self-Report Scale (ASRS) v.1.1 together with eight neuropsychological tests were investigated. RESULTS: All instruments showed poor discriminative ability except for the DIVA, which showed a relatively good ability to discriminate between the groups (sensitivity = 90.0; specificity = 72.9). A logistic regression analysis model with the DIVA and measures of inattention, impulsivity, and activity from continuous performance tests (CPTs) showed a sensitivity of 90.0 and a specificity of 83.3. CONCLUSION: Neuropsychological tests have a poor ability to discriminate between patients diagnosed with ADHD and patients not diagnosed with ADHD, but variables from CPT tests can contribute to increasing the specificity by 10% if used in combination with the DIVA. PMID- 26681531 TI - Generation of cardiac pacemaker cells by programming and differentiation. AB - A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26681533 TI - Enhanced Eryptosis Following Exposure to Lopinavir. AB - BACKGROUND/AIMS: The protease inhibitor lopinavir, used for the treatment of HIV infections, triggers suicidal death or apoptosis of nucleated cells. Side effects of lopinavir include anemia, which could in theory result from stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and by phospholipid scrambling of the cell membrane leading to phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether lopinavir induces eryptosis. METHODS: Flow cytometry was employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from 2',7' dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, reduced glutathione (GSH) from mercury orange fluorescence and ceramide abundance utilizing labelled specific antibodies. Hemolysis was estimated from haemoglobin concentration of the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to lopinavir significantly increased the percentage of annexin-V-binding cells (>= 10 ug/ml), significantly decreased forward scatter (>=15 ug/ml), significantly increased hemolysis (>= 15 ug/ml), significantly increased Fluo3-fluorescence (20 ug/ml), and significantly increased DCFDA fluorescence (20 ug/ml) but did not significantly modify ceramide abundance. The effect of lopinavir on annexin-V binding was significantly blunted, but not abolished by removal of extracellular Ca2+. CONCLUSION: Lopinavir treatment of erythrocytes from healthy volunteers is followed by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of ROS formation and Ca2+ entry. PMID- 26681534 TI - What are the potential limitations of drug coated balloons (DCBs) and possible ways to overcome. AB - In several independent randomized clinical studies, it has been shown that DCBs cause persistent clinically meaningful and statistically significant inhibition of restenosis in femoropopliteal arteries in comparison to percutaneous transluminal angioplasty with uncoated balloon catheters (1-6). The potential benefits of delivering an antiproliferative drug into the vessel wall using a balloon as transporter are manifold: * Widespread applicability: Balloon angioplasty is suitable for use in a wide range of lesions. The use of DCBs is technically less demanding and offers greater flexibility compared with stenting techniques. * Maintaining options: Minimizing the use of durable implants is providing more options for following and complementary revascularization procedures. * Proven Efficacy: Consistent, positive outcomes across studies and key subgroups have been demonstrated from the first preclinical studies to ongoing clinical trials Beside the enthusiasm carried along with this novel technique and questioning if DCBs will become standard-of-care-therapy for the superficial femoral artery (SFA), the potential limitations have to be discussed. PMID- 26681532 TI - Normal hematopoiesis and lack of beta-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations. AB - Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of beta-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of beta-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require beta-catenin signaling, particularly, the deregulation of hematopoiesis and leukemogenic properties of beta-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate beta-catenin signaling in osteoblasts. Consistent with a lack of beta-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of beta-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate beta-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. PMID- 26681535 TI - Drug coated balloons in BTK - just too early? AB - Patients with infra-popliteal arterial disease are generally considered challenging due to the usual presence of multi-vessel atherosclerotic disease. Several treatment options have been used by different authors but none of them can be considered ideal. In the last few years drug coated balloons have gained popularity especially due to the extraordinary results in the femoro-popliteal region. Following the great success, phisicians started to use this promising device also in the below-the-knee (BTK) region. The initial enthusiasm correlated to some studies is not confirmed by the largest randomized trial, IN.PACT Deep, comparing In.Pact DCB vs. standard PTA. This trial failed completely to show the superiority of DCB.The negative outcome was mainly correlated to safety issues with an amputation rate higher for the drug coated balloon when compared to the conventional balloon (8.8% DCB vs 3.6% PTA, p=0.08). A thorough evaluation has been performed to justify these negative outcomes, given the good results reported by other studies. But nowadays is still difficult to find a clear explanation. Especially for this negative outcome and for the big difference, in term of results, beteween the different studies in the BTK region and also betwenn the above and below the knee regions more trials are mandatory. PMID- 26681536 TI - How does a drug-coated balloon work? Overview about coating technologies and their impact. AB - BACKGROUND: According to current understanding the drug-coated balloon carries a sufficient dose of an effective antineoplastic agent, i.e. paclitaxel, to the target lesion. METHODS: Literature review and report on experimental studies simulating the access of coated balloons to the treatment site and studies in pigs. RESULTS: The drug adheres to the balloon membrane and is partially hidden below the folds which are wrapped around the shaft. Upon inflation solid paclitaxel particles are pushed into the vessel wall. Premature loss of paclitaxel and transfer to the vessel wall is controlled by the formulation including an inactive additive. Particles in the tissue dissolve slowly resulting in a terminal half-life of almost 2 months. Premature loss of the drug, dissolution, elimination, efficacy and tolerance are limited by the very low solubility of paclitaxel. From exemplary DCB approximately 10% of drug is lost before the target lesion is reached, 5-20% is transferred into the vessel wall and 10% remain on the balloon after withdrawal. The difference is distributed in the general circulation. Inhibition of neointimal proliferation in animal models is reliable and as persistent as with drug-eluting stents. Histology reveals slight to moderate dose-dependent downstream effects without functional or clinical symptoms. CONCLUSION: For the time being paclitaxel remains the drug of choice, the dose varies between 2 and 3.5 MUg/mm2 balloon surface. Neither in animal experiments nor in clinical trials problems have been detected in vessel segments treated with overlapping balloons. Future developments are expected improving efficacy in additional disease conditions (e.g., calcified vessels) and vessel territories. PMID- 26681538 TI - Deployed but not irretrievable: A novel surgical off-pump technique for parachute device extraction. PMID- 26681539 TI - Exercise testing can unmask right ventricular dysfunction in systemic sclerosis patients with normal resting pulmonary artery pressure. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a frequent complication of systemic sclerosis (SSc). Diagnosis usually occurs late and often after the development of irreversible right heart dysfunction. Exercise testing is increasingly used for assessing right ventricular (RV) function when resting hemodynamics do not account for symptoms. We hypothesized that SSc patients without resting pulmonary hypertension could have impaired exercise capacity and RV contractile reserve with exercise thus unmasking early RV dysfunction and pulmonary vascular disease. METHODS: Treadmill exercise stress echocardiography with concurrent expired gas analysis was performed in 25 SSc patients with normal resting pulmonary arterial pressure (PAP) and healthy controls (n = 50). Additionally, controls and SSc patients were compared to those with established PAH (n = 23). Parameters of RV systolic function (RV fractional area change (FAC), Doppler tissue (DTI) s' velocity, systolic strain and strain rate (S-Sr)) were evaluated at baseline and post-exercise with the difference (Delta) being contractile reserve. RESULTS: RV contractile reserve was reduced in the SSc group with normal resting PAP, compared with healthy controls (Deltas': 6.1 +/- 2.3 vs 8.0 +/- 2.2 cm s(-1), p < 0.001; and DeltaS-Sr: 2.3 +/- 0.5 vs 2.6 +/- 0.2s(-1), p = 0.02) in association with a significantly higher mean PAP with exercise (25.5 +/- 6.6 vs 19.9 +/- 7.2 mmHg, p < 0.001). PAH patients demonstrated the lowest levels of contractile reserve (Deltas', Delta strain, DeltaS-Sr and DeltaFAC, all p < 0.05). CONCLUSION: Exercise stress testing unmasks reduced RV contractile reserve in SSc patients with normal resting PAP. Subclinical RV dysfunction during exercise may be a surrogate for early pulmonary vascular disease in SSc patients. PMID- 26681540 TI - Relative dose and vascular response after drug-eluting stent implantation: A dosimetric 3D-intravascular ultrasound study. AB - BACKGROUND: In drug-eluting stents (DESs), the theoretical drug dose exposed to the vessel wall per stent surface area may vary due to the fixed loading dose and differences in the stent surface area once expanded in varying vessel sizes. The aim of this study was to evaluate the potential effects of different dose intensities, as estimated by 3D-IVUS dosimetry, on vascular response after DES implantation. METHODS: Follow-up (6-9 months) 3D-IVUS was performed in 840 coronary lesions treated with a single DES of the following types: sirolimus (SES, n=148), paclitaxel (PES, n=162), Endeavor zotarolimus (E-ZES, n=233), Resolute zotarolimus (R-ZES, n=147), and everolimus (EES, n=150). Volume index (volume/length, mm(3)/mm) was obtained for vessel, lumen, plaque, stent, and neointima. In each lesion, exposed dose intensity was calculated as known loading dose divided by measured luminal surface area of the stented segment. Lesions were divided into tertiles based on the exposed dose intensity: high, medium, and low dose groups. RESULTS: The exposed dose intensity ranged 0.74-1.76 MUg/mm(2) for SES, 0.41-1.18 MUg/mm(2) for PES, 0.71-1.57 MUg/mm(2) for E-ZES, 0.72-1.63 MUg/mm(2) for R-ZES, and 0.40-0.99 MUg/mm(2) for EES. All types of DES showed no significant difference in neointimal hyperplasia among the 3 groups, except that E-ZES showed significantly less neointimal hyperplasia in the high dose group. CONCLUSIONS: Detailed 3D-IVUS revealed significant lesion-to-lesion variability in dose intensity exposed to the vessel wall following DES implantation. However, the major types of DES appear to yield equally effective neointimal suppression, despite the varying dose intensity, except for E-ZES. PMID- 26681537 TI - Cardiac Troponins in Dogs and Cats. AB - Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conventionally, the cardiac troponins have been used for diagnosis of acute myocardial infarction in humans and have become the gold standard biomarkers for this indication. They have become increasingly recognized as an objective measure of cardiomyocyte status in both cardiac and noncardiac disease, supplying additional information to that provided by echocardiography and ECG. Injury to cardiomyocytes can occur through a variety of mechanisms with subsequent release of troponins. Independent of the underlying disease or the mechanism of troponin release, the presence of myocardial injury is associated with an increased risk of death. As increasingly sensitive assays are introduced, the frequent occurrence of myocardial injury is becoming apparent, and our understanding of its causes and importance is constantly evolving. Presently troponins are valuable for detecting a subgroup of patients with higher risk of death. Future research is needed to clarify whether troponins can serve as monitoring tools guiding treatment, whether administering more aggressive treatment to patients with evidence of myocardial injury is beneficial, and whether normalizing of troponin concentrations in patients presenting with evidence of myocardial injury is associated with reduced risk of death. PMID- 26681541 TI - Predictive factors of long-term results following valve repair in ischemic mitral valve prolapse. AB - BACKGROUND: In patients with ischemic mitral regurgitation, leaflet prolapse requires an accurate evaluation since surgical approach depends on valvular and subvalvular characteristics. This study aims to describe a cohort of patients over a long-term follow up, analyzing survival, reoperation and predictive factors of surgical outcomes. METHODS AND RESULTS: From March 1994 to June 2011, 75 patients with ischemic mitral regurgitation and leaflet prolapse underwent surgical myocardial revascularization and mitral valve repair (90.7%) or replacement (9.3%). Our cohort was followed up until April 2015, with a mean follow up of 7 +/- 3 years. Cardiac-related deaths occurred in 26 patients, with a mean survival of 114.2 months, including eight patients with in-hospital mortality. Reoperation was performed in 14 patients, due to valve repair failure. Twenty-six patients experienced moderate-to-severe mitral regurgitation. A preoperative LVEDD > 62 mm, LVESD > 52 mm, previous anteroseptal myocardial infarction, diffuse coronary artery disease, papillary anatomy type 1, partial rupture of the papillary muscle, A1-A2 scallop prolapse and postoperative mitral valve configuration (tenting area, tenting height, alfa-1 angle and alfa-2 angle) were identified as independent predictors of poor outcome. An index quantifying the stress on the annulus imparted by annuloplasty was elaborated and predicted endpoints. CONCLUSION: Leaflet prolapse is an important entity in patients with ischemic mitral regurgitation, and its pathogenic mechanism mostly relies on papillary muscle lesion or elongation. Perioperative parameters describing geometric features of left ventricle, valvular and subvalvular components should be considered to provide a tailored approach for mitral valve repair, or to opt for immediate replacement in case of unfavorable geometry. PMID- 26681542 TI - Overexpression myocardial inducible nitric oxide synthase exacerbates cardiac dysfunction and beta-adrenergic desensitization in experimental hypothyroidism. AB - BACKGROUND: Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and beta-adrenergic hyporesponsiveness. METHODS AND RESULTS: We simultaneously evaluated LV functional performance and compared myocyte three NOS, beta-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca(2+)]iT responses to beta-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10(-5)mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca(2+)]iT. In hypothyroidism, isoproterenol (10(-8)M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca(2+)]iT. These changes were associated with decreased beta1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol stimulated myocyte contraction, relaxation and [Ca(2+)]iT. CONCLUSIONS: Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with beta-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. PMID- 26681543 TI - Community participation of persons with disabilities: volunteering, donations and involvement in groups and organisations. AB - PURPOSE: This study examined similarities and differences between persons with and without disabilities on volunteering, donations and group participation. METHOD: A sample of 1548 individuals participated and 60% of the sample were persons with disabilities. Data for this research was drawn from a major statewide survey in a Midwestern state in the United States. Community participation was measured through involvement with civic, religious and other community-based groups, volunteering activities and donations. Logistic regression was pursued to test the effect of disability on community participation. RESULTS: Findings support different trends in participation between persons with and without disabilities. Individuals without disabilities are more likely to volunteer, donate money and participate in civic organisations (e.g. clubs) and other groups. Employment and household income have a significant contribution in explaining these differences. CONCLUSIONS: This study found significant differences in community participation between persons with disabilities and persons without disabilities. Regression analysis outcomes underscore the importance of employment and income in eliminating disparities in community involvement between persons with and without disabilities. Implications for Rehabilitation Policy change in rehabilitation agencies to fund supported volunteering services. Improve the representation of persons with disabilities in volunteering pursuits by making volunteering positions accessible to them (educate persons with disabilities to be more aware of these opportunities, provide reasonable accommodations at work sites, etc.). Educate stakeholders about the benefits of volunteering and being part of civic, and other community based groups in improving the quality of life of persons with disabilities. Identification of barriers for persons with disabilities in these pursuits (physical and attitudinal barriers, lack of resources). Identifying and utilising natural supports in the work site for persons with disabilities to receive peer support on the job from full-time employees. PMID- 26681544 TI - Detection of differentially methylated regions from bisulfite-seq data by hidden Markov models incorporating genome-wide methylation level distributions. AB - BACKGROUND: Detection of differential methylation between biological samples is an important task in bisulfite-seq data analysis. Several studies have attempted de novo finding of differentially methylated regions (DMRs) using hidden Markov models (HMMs). However, there is room for improvement in the design of HMMs, especially on emission functions that evaluate the likelihood of differential methylation at each cytosine site. RESULTS: We describe a new HMM for DMR detection from bisulfite-seq data. Our method utilizes emission functions that combine binomial models for aligned read counts, and beta mixtures for incorporating genome-wide methylation level distributions. We also develop unsupervised learning algorithms to adjust parameters of the beta-binomial models depending on differential methylation types (up, down, and not changed). In experiments on both simulated and real datasets, the new HMM improves DMR detection accuracy compared with HMMs in our previous study. Furthermore, our method achieves better accuracy than other methods using Fisher's exact test and methylation level smoothing. CONCLUSIONS: Our method enables accurate DMR detection from bisulfite-seq data. The implementation of our method is named ComMet, and distributed as a part of Bisulfighter package, which is available at http://epigenome.cbrc.jp/bisulfighter. PMID- 26681545 TI - Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model. AB - The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. PMID- 26681546 TI - Can galectin-3 be a useful marker for conventional papillary thyroid microcarcinoma? AB - BACKGROUND: Galectin-3 staining of fine-needle aspiration (FNA) samples is very useful for diagnosis of thyroid malignancy. As reported in several studies, galectin-3 is associated with prognostic factor in papillary thyroid carcinoma, but its expression and prognostic role has not been evaluated in papillary microcarcinoma (PTMC). This study was performed to investigate the prevalence of galectin-3 in preoperative ultrasonography (US)-guided FNA cytology and to evaluate the association between galectin-3 expression and prognostic factors of PTMC. METHODS: Between January 2011 and December 2012, 440 conventional PTMCs which had undergone US-guided FNA with galectin-3 analysis and underwent subsequent surgery were enrolled. Preoperative US features and clinicopathologic results including extrathyroidal extension and lymph node metastasis were compared between galectin-3 positive and galectin-3 negative PTMC. RESULTS: Of the 440 PTMCs, 201 (45.7%) PTMCs had galectin-3 positivity in preoperative FNA samples. There was no significant difference in US features between galectin-3 positive and negative PTMC. Galectin-3 expression had no significant association with prognostic factors such as extrathyroidal extension (44.8% vs. 44.8%, P = 0.999) and lymph node metastasis (25.9% vs. 26.8%, P = 0.914) in conventional PTMC. CONCLUSION: Preoperative galectin-3 analysis using FNA cytology may be not advisable in patients with conventional PTMC. PMID- 26681547 TI - Endocrinopathies induced by immune-checkpoint inhibitors in advanced non-small cell lung cancer. AB - The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications. Among these, a spectrum of endocrine disorders has been also reported. This manuscript focuses particularly on endocrine disorders induced by immuno-checkpoint inhibitors employed in NSCLC, in order to suggest the strategies for their diagnosis and effective management. PMID- 26681548 TI - Exposure risk of young population to lead: A case study in Le'an River Basin in Jiangxi Province, China. AB - Blood lead (Pb) level of children has widely been attracting public concern in China, particularly in the sites near mining or industrial areas. However, the policies about how to efficiently reduce the Pb intake of children are still under discussion. We collected six food types based on the local dietary habits and soils from Dexing, Leping, and Poyang Counties situated along the Le'an River Basin from upstream to downstream, and their Pb contents were analyzed. A Monte Carlo model was used to simulate the dietary chronic daily intake of Pb (CDIPb) from various foods and ingested soil by hand-to-mouth activities and its non carcinogenic risk to children indicated by hazard quotient (HQ). Only in the rural area of Dexing, its soil and vegetables both had higher Pb content than the national tolerance limits of China, resulting its the highest CDIPb among all the areas. The Pb contents of the six food types and soils in other sites were overall below the limits. Vegetables and rice accounted for from 63% (Leping, urban) to 85% (Dexing, rural) of the total CDIPb and ingested soil overall took up ~6%. In the rural area, Dexing had the highest proportion (82.8%) of children with HQ > 1, followed by Leping (36.1%) and Poyang (27.7%). Different order was found in the urban areas, i.e. Dexing (46.7%) > Poyang (41.0%) > Leping (26.4%). Vegetables and rice were overall the two major contributors to the total CDI of Pb, which should be focused on to control the Pb intake by the local children, especially for those living in the rural area of Dexing County. PMID- 26681550 TI - Zerumbone Suppresses Osteopontin-Induced Cell Invasion Through Inhibiting the FAK/AKT/ROCK Pathway in Human Non-Small Cell Lung Cancer A549 Cells. AB - Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in the United States and Korea. We have previously demonstrated that osteopontin (OPN) induces cell invasion through inactivating cofilin. Inactivation of cofilin is mediated by the FAK/AKT/Rho-associated kinase (ROCK) pathway in human nonsmall cell lung cancer (NSCLC) cells. Zerumbone (1) has been shown to exert anticancer activities. In this study, whether and how 1 affects OPN-induced cell invasion was determined in NSCLC A549 cells. Results from Boyden chamber assays suggested that OPN induced invasion of A549 cells and that 1 strongly suppressed this activity without affecting cell viability. Compound 1 effectively inhibited OPN-induced protein expression of ROCK1, the phosphorylation of LIM kinase 1 and 2 (LIMK1/2), and cofilin. In addition, immunofluorescence staining showed that OPN caused a significant increase in lamellipodia formation at the leading edge of cells. However, 1 dramatically decreased OPN-induced lamellipodia formation. Compound 1 impaired OPN-induced phosphorylation of FAK and AKT, as determined by Western blot analysis. Taken together, these results suggest that 1 causes considerable suppression of OPN induced cell invasion through inhibiting the FAK/AKT/ROCK pathway in NSCLC A549 cells. PMID- 26681551 TI - A vanadium-doped ZnO nanosheets-polymer composite for flexible piezoelectric nanogenerators. AB - We report high performance flexible piezoelectric nanogenerators (PENGs) by employing vanadium (V)-doped ZnO nanosheets (NSs) and the polydimethylsiloxane (PDMS) composite structure. The V-doped ZnO NSs were synthesized to overcome the inherently low piezoelectric properties of intrinsic ZnO. Ferroelectric phase transition induced in the V-doped ZnO NSs contributed to significantly improve the performance of the PENGs after the poling process. Consequently, the PENGs exhibited high output voltage and current up to ~32 V and ~6.2 MUA, respectively, under the applied strain, which are sufficient to directly turn on a number of light emitting diodes (LEDs). The composite approach for PENG fabrication is scalable, robust, and reproducible during periodic bending/releasing over extended cycles. The approach introduced here extends the performance limits of ZnO-based PENGs and demonstrates their potential as energy harvesting devices. PMID- 26681552 TI - Compact Wireless Microscope for In-Situ Time Course Study of Large Scale Cell Dynamics within an Incubator. AB - Imaging of live cells in a region of interest is essential to life science research. Unlike the traditional way that mounts CO2 incubator onto a bulky microscope for observation, here we propose a wireless microscope (termed w SCOPE) that is based on the "microscope-in-incubator" concept and can be easily housed into a standard CO2 incubator for prolonged on-site observation of the cells. The w-SCOPE is capable of tunable magnification, remote control and wireless image transmission. At the same time, it is compact, measuring only ~10 cm in each dimension, and cost-effective. With the enhancement of compressive sensing computation, the acquired images can achieve a wide field of view (FOV) of ~113 mm(2) as well as a cellular resolution of ~3 MUm, which enables various forms of follow-up image-based cell analysis. We performed 12 hours time-lapse study on paclitaxel-treated MCF-7 and HEK293T cell lines using w-SCOPE. The analytic results, such as the calculated viability and therapeutic window, from our device were validated by standard cell detection assays and imaging-based cytometer. In addition to those end-point detection methods, w-SCOPE further uncovered the time course of the cell's response to the drug treatment over the whole period of drug exposure. PMID- 26681553 TI - Proximal hamstring morphology and morphometry in men: an anatomic and MRI investigation. AB - The proximal musculo-tendinous junction (MTJ) is a common site of hamstring strain injury but the anatomy of this region is not well defined. A morphometric analysis of the proximal MTJs of biceps femoris long head (BFlh), semitendinosus (ST), and semimembranosus (SM) was undertaken from dissection of 10 thighs from five male cadavers and magnetic resonance imaging of 20 thighs of 10 active young men. The length, volume, and cross-sectional area of the proximal tendon, MTJ and muscle belly, and muscle-tendon interface area were calculated. In both groups, MTJs were reconstructed three-dimensionally. The proximal tendons and MTJs were expansive, particularly within SM and BFlh. Morphology varied between muscles although length measurements within individual muscles were similar in cadavers and young men. Semimembranosus had the longest proximal tendon (cadavers: mean 33.6 +/- 2.0 cm; young men: mean 31.7 +/- 1.6 cm) and MTJ (>20 cm in both groups) and the greatest muscle-tendon interface area, followed by BFlh and ST. Mean muscle belly volumes were more than three times greater in young men than elderly male cadavers (P < 0.001). These unique morphometric data contribute to a better understanding of hamstring anatomy, an important factor in the pathogenesis of hamstring strain injury. PMID- 26681554 TI - CtBP2 Regulates TGFbeta2-Induced Epithelial-Mesenchymal Transition Through Notch Signaling Pathway in Lens Epithelial Cells. AB - BACKGROUND: Epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs) contributes to posterior capsule opacification (PCO). C-terminal binding protein 2 (CtBP2) has been reported to be essential in EMT and embryonic development. However, the function of CtBP2 in EMT of LECs is unknown. The goal of this study was to investigate the role of CtBP2 through Notch signaling in transforming growth factor beta2 (TGFbeta2)-induced EMT in LECs. METHODS: The human LEC line SRA01/04 was cultured in the presence of TGFbeta2 for different periods of time or with gamma-Secretase Inhibitor IX (DAPT), a specific inhibitor of Notch receptor cleavage, for 24 h, utilizing plasmid-based method. The levels of protein expression of CtBP2, EMT markers, and Notch signaling molecules were measured by Western bolts. RESULTS: Treatment of SRA01/04 cells with TGFbeta2 induced typical molecular changes of EMT and increased the expression of CtBP2 in a time-dependent manner. Similarly, the expressions of Jagged1 and Notch1 were increased after TGFbeta2 treatment. Knockdown of CtBP2 by specific siRNA inhibited TGFbeta2-induced changes of Connexin 43 (CX43), alpha-smooth muscle actin (alpha-SMA), Notch1, and Notch intracellular domain (NICD). In addition, treatment of LECs with ectopic expression of CtBP2 changed the expressions of CX43, alpha-SMA, Notch1, and NICD, but blockade of Notch pathway with DAPT inhibited CtBP2-induced changes of alpha-SMA and CX43. CONCLUSION: Our data suggest that CtBP2 plays a critical role in TGFbeta2-induced EMT via the Jagged/Notch signaling pathway in human LECs and may contribute to the development of PCO. PMID- 26681556 TI - Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca. AB - The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeast + cereal leaf + trout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatoms + TetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20] = 13 MUg/L and 15 MUg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 ug/L, but these endpoints were significantly reduced by Pb in the YCT test and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model-normalized effect concentrations for the 3 tests ranged from 3.7 MUg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 MUg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes. Environ Toxicol Chem 2016;35:1825-1834. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and as such, is in the public domain in the United States of America. PMID- 26681557 TI - New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry. AB - BACKGROUND/AIMS: New-onset diabetes after transplantation (NODAT) is a serious complication of liver transplantation (LT). The present study aimed to investigate the risk factors of NODAT by a national survey using the China Liver Transplant Registry database. PATIENTS: A total of 10 204 non-pre-existing diabetic patients undergone primary LT between January 2000 and December 2013 were included. Risk factors were identified by logistic regression analysis. RESULTS: NODAT occurred in 24.3% of liver recipients with a median follow-up time of 2.6 years, and was associated with a significantly lower patient survival. NODAT increased not only diabetes related complications (e.g., infection, kidney failure) but also biliary stricture and cholangitis. NODAT patients who received hypoglycaemic treatment had a worse prognosis and a higher hepatocellular carcinoma recurrence compared with those without treatment. New-onset hyperglycaemia (<30 days) was the major predictor of NODAT. Other risk factors included cold ischaemia time >9 h, recipient age >50 years, body mass index >25 kg/m(2) , other hepatitis (mainly hepatitis C), post-transplant intensive care unit stay >15 days, cytomegalovirus infection and corticosteroid at discharge. CONCLUSIONS: The incidence of NODAT in China is similar to that in Western countries. However, the NODAT-related complications are more common and severer in China compared with those in Western countries. The major risk factors are different. PMID- 26681570 TI - Long-term outcomes in medial flap inferior turbinoplasty are superior to submucosal electrocautery and submucosal powered turbinate reduction. AB - BACKGROUND: Techniques for inferior turbinate reduction vary from complete turbinectomy to limited cauterization. Surgical methods differ on the degree of tissue reduction and reliance on surgical tissue removal vs tissue ablation. The outcome and morbidity from 3 different turbinate techniques are compared. METHODS: A randomized double-blinded study was performed. Patient nasal cavities were randomized to different interventions on each side within the same patient. One group had a combination of submucosal powered turbinate reduction (designated "submucosal") and submucosal electrocautery (designated "electrocautery"); and the second group had a combination of submucosal powered turbinate reduction (designated "submucosal") and medial flap turbinoplasty (designated "turbinoplasty"). Patient-scored nasal obstruction and rhinorrhoea (1 to 5) along with blindly assessed nasal airway patency ratings (1 to 4) was done at 12 and 60 months postoperatively. Pain requiring additional analgesia, crusting, bleeding (needing review), and revision were documented. RESULTS: A total of 100 patients were recruited (age 32.79 +/- 13.58 years; 39% female). This represented 200 nasal airway surgeries with 100 submucosal procedures, 50 electrocautery and 50 medial flap turbinoplasties. No patients complained of worsening of their obstruction. At 60 months patients in the turbinoplasty group had greater outcomes, with 90.2% having occasional or no decongestant use (Kendall's tau B p < 0.001) compared to electrocautery (15.8%) and submucosal (37.8%). Fewer turbinoplasty patients had a revision procedure (12%, chi(2) = 20.08, p < 0.001) compared to electrocautery (54%) and submucosal (40%). Crusting was more common in the electrocautery group (58% vs submucosal 2% and turbinoplasty 0%; chi(2) = 92.04; p < 0.001). CONCLUSION: The medial flap turbinoplasty provided consistent, robust results. Long-term relief of obstructive symptoms without additional risk of complication was observed in the turbinoplasty group. PMID- 26681571 TI - Rechallenging With Intrathecal Methotrexate After Developing Subacute Neurotoxicity in Children With Hematologic Malignancies. AB - Methotrexate is associated with neurologic side effects. It is recommended that patients who developed neurotoxicity be rechallenged with methotrexate, but little is known about the safety of this approach. We performed a chart review to identify patients who received high-dose or intrathecal (IT) methotrexate. Twenty one of 298 patients (7%) experienced neurologic symptoms attributed to methotrexate treatment in the premaintenance phase. Seventeen of these patients were rechallenged with IT methotrexate and 13 (76%) had no further neurotoxic events. No patients rechallenged during maintenance (n = 9) experienced recurrence of neurotoxic events. It is safe to rechallenge with IT methotrexate in maintenance. PMID- 26681572 TI - Effect of training frequency on the learning curve on the da Vinci Skills Simulator. AB - BACKGROUND: The purpose of this study was to evaluate the effect of training on the performance outcome with the da Vinci Skills Simulator. METHODS: Forty novices were enrolled in a prospective training curriculum. Participants were separated into 2 groups. Group 1 performed 4 training sessions and group 2 had 2 training sessions over a 4-week period. Five exercises were performed 3 times consecutively. On the last training day, a new exercise was added. RESULTS: A significant skills gain from the first to the final practice day in overall performance, time to complete, and economy of motion was seen for both groups. Group 1 had a significantly better outcome in overall performance, time to complete, and economy of motion in all exercises. There was no significant difference found regarding the new exercise in group 1 versus group 2 in nearly all parameters. CONCLUSION: Longer time distances between training sessions are assumed to play a secondary role, whereas total repetition frequency is crucial for improvement of technical performance. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1762-E1769, 2016. PMID- 26681573 TI - Labour duration and timing of interventions in women planning vaginal birth after caesarean section. AB - OBJECTIVE: understanding the labour characteristics of women attempting vaginal birth after caesarean (VBAC) may suggest how to improve intrapartum management and may enhance success rates. Promoting VBAC is a relevant factor in decreasing overall caesarean section (c-section) rates. However, the labour processes of women attempting VBAC are not well investigated. The aim of this paper is to compare multiparae planning a first VBAC (pVBAC) with primiparae and with multiparae planning a second vaginal birth, all starting to give birth vaginally, with regard to (a) perinatal characteristics, (b) the timing of intrapartal spontaneous rupture of membranes (SROM) and of interventions, and (c) labour duration, with respect to the first and second stages. SETTING: cohort study of women planning vaginal birth in 47 obstetric units in Lower Saxony, Germany. PARTICIPANTS: 1897 primiparae, 211 multiparae with one previous c-section and 1149 multiparae with one previous vaginal birth. MEASUREMENTS: secondary analysis of data from an existing cohort study. Kaplan-Meier estimates, log rank test, Wilcoxon test and shared frailty Cox regression models including time-varying covariates were used to compare the timing of interventions and labour duration between the subsamples. Analyses were done with the statistics programme Stata 13. FINDINGS: perinatal and labour characteristics of multiparae with pVBAC mainly resembled those of primiparae and differed from those of multiparae planning a second vaginal birth. However, compared to primiparae, multiparae with pVBAC received oxytocin less often (48.82 versus 56.95%, p=0.024) and gave birth vaginally significantly less often (69.19 versus 83.40%, p<0.001). The timing of intrapartal SROM (2.67 versus 3.42 hours, p=0.112) and of interventions (amniotomy: 5.50 versus 5.83 hours, p=0.198; oxytocin: 5.75 versus 6.00 hours, p=0.596; epidural: 4.00 versus 4.67 hours, p=0.416; opioids: 3.83 versus 3.78, p=0.851) was similar to that in primiparae although timings of all interventions but not of SROM differed significantly from that in multiparae with second vaginal birth (SROM: 2.67 versus 2.67 hours, p=0.481; amniotomy: 5.50 versus 3.93 hours, p<0.001; oxytocin: 5.75 versus 4.25 hours, p<0.001; epidural: 4.00 versus 3.50 hours, p=0.009; 3.83 versus. 2.75 hours, p=0.026). Overall and first-stage labour duration were comparable to primiparae (overall labour duration: 8.83 versus 8.57 hours, HR=0.998, 95% CI=0.830-1.201, p=0.987; first stage: 7.42 versus 7.00 hours, HR=0.916, 95% CI=0.774-1.083, p=0.303) but significantly longer than in other multiparae (overall labour duration: 8.83 versus 4.63 hours, HR=0.319, 95% CI=0.265-0.385, p<0.001; first stage: 7.42 versus 4.25 hours, HR=0.402, 95% CI=0.339-0.478, p<0.001). However, the second stage of labour was significantly shorter in multiparae with pVBAC than in primiparae (0.55 versus 0.77 hours, HR=1.341, 95% CI=1.049-1.714, p=0.019), but longer than in multiparae with second vaginal birth (0.55 versus 0.22 hours, HR=0.334, 95% CI=0.262-0.426, p<0.001). KEY CONCLUSION: labour patterns of multiparous women planning a VBAC differ from those of primiparae and other multiparous women. Multiparae with pVBAC should be considered as a distinct group of parturients. IMPLICATION FOR PRACTICE: expectations regarding labour progression for multiparae with first pVBAC should be similar to those for primiparae. However, the chance that the second stage of labour might be shorter than in primiparae is relevant and motivating information for pregnant women with a previous c-section in deciding the planned mode of birth. PMID- 26681574 TI - Autonomic dysfunction elicited by a medulla oblongata injury after fourth ventricle tumor surgery in a pediatric patient. AB - We report the case of a 9-year-old male patient with a recurrent fourth ventricle anaplastic ependymoma who developed severe arterial hypertension and blood pressure lability during and after surgery. A punctual bilateral lesion located within mid dorsal medulla oblongata caused by both infiltration and surgical resection was observed in postoperative MRI. Three years later, the patient remained neurologically stable but the family referred the presence of a chronic tachycardia as well as palpitations and sweating with flushing episodes related to environmental stress. On autonomic evaluation, an increase in sympathetic outflow with tachycardia together with orthostatic hypotension caused by baroreceptor reflex dysfunction was observed. We postulate that a bilateral injury to both nuclei of the solitary tract may have caused central dysautonomia. PMID- 26681575 TI - EEG beta power and heart rate variability describe the association between cortical and autonomic arousals across sleep. AB - Cortical and autonomic arousals have been found to be closely associated. As arousal events are not evenly dispersed across sleep, we hypothesized the relationship between high frequency electroencephalogram (EEG) power and autonomic arousal indices differ between non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. One night of polysomnographic recording was performed on a group of 18 subjects using a portable recorder. The EEG was collected from C3/Fz. Sleep stages and cortical arousals were visually scored. Cardiac autonomic modulation was assessed from heart rate variability, where the high frequency power (HF) indicates parasympathetic modulation, and the low frequency to high frequency power ratio (LF/HF) represents sympathetic modulation. During NREM sleep, EEG beta power was significantly correlated with LF/HF (r=0.40 +/- 0.06), and the relationships were more positive than during REM sleep (LF/HF: r=0.20 +/- 0.08; EOG power: r=-0.13 +/- 0.05). The relationship of beta power with LF/HF was associated with the incidence of cortical arousal, particularly during NREM sleep. With respect to alpha power, it was only marginally related to HF or LF/HF. In addition, the coefficients of determination were lower for alpha power than for beta power in terms of the relationships to HF, LF/HF and EOG power. This study shows a higher relationship between cortical and autonomic activation during NREM sleep, and the association is better described by beta power. This finding suggests NREM sleep may be of greater therapeutic potential in view of reducing cardiovascular disease associated with sleep fragmentation, and beta power may provide a better index to evaluate the effect. PMID- 26681576 TI - [Impact of the acquisition of a flexible ureteroscope on the management of upper urinary tract stones in children]. AB - INTRODUCTION: Firstly reported in the early 1990s for the treatment of upper urinary tract stones in adult patients, flexible ureteroscopy (F-URS) has been used in children during the past 10 years and is now considered as a viable, but still second-line alternative to extracorporeal shockwave lithotripsy in these patients (ESWL). The aim of this study was to assess the impact of the acquisition of a F-URS on the management of upper urinary tract stones in children. PATIENTS AND METHODS: Data of all ESWL, F-URS and percutaneous nephrolithotomy performed for upper urinary tract stones in children from 0 to 18 years old in a single center from 2000 to 2014 have been collected retrospectively. Patients have been divided into two groups: group 1 before the acquisition of the F-URS (2000-2008) and group 2 after the acquisition of the F URS (2008-2014). Preoperative data and peri-operative outcomes were compared between both groups using the chi(2) test and Fisher exact test for discrete variables and the Mann-Whitney test for continuous variables. RESULTS: Thirty seven children have been treated during the first era and 32 during the second one. The two groups were similar in terms of age (7.2 years vs 8.1 years; P=0.54), size of the largest stone (15 mm vs 16.2mm; P=0,56) and number of stones per patient (1.4 vs 2; P=0,07) but the sum of stone diameters was higher in group 2 (16.9 mm vs 24.2mm; P=0,048). The stone-free rates were comparable in both groups (28.1% vs 32.2% after the first procedure; P=0.72), as were the mean number of procedures per patient (2.4 vs 2.5; P=0.78), the total length of stay (2.7 days vs 2.9 days; P=0.77), and the number of patients who experienced at least one complication (37.8% vs 40.6%; P=0.87). CONCLUSION: The acquisition of a F-URS allowed the treatment of more complex stones with a similar efficacy and without increasing morbidity. Further studies are needed to define the role of F URS in the management of upper urinary tract stones in children. PMID- 26681577 TI - Preventing Alcohol Abuse Through Social Networking Sites: A First Assessment of a Two-Year Ecological Approach. AB - BACKGROUND: Prevention strategies to reduce alcohol use/consumption among young people are crucial to reducing alcohol-related deaths and preventing disease. This paper focuses on the effectiveness of a social networking site (SNS) alcohol prevention program targeted toward young people. OBJECTIVE: We hypothesized that the program would diminish the relation made by participants between alcohol and festive moments, and would result in a reduction of their declared consumption of alcohol at festive moments during the program. We also explored the interaction with the prevention program that was the most efficient. METHODS: The prevention program took the form of 3 lotteries over 2 years. The participants periodically received prevention messages, particularly on alcohol and festive moments (eg, videos on Facebook and short message service [SMS] text messages on their mobile phones). For the 3 periods, the participants had to answer questions exploring the level of their belief that alcohol consumption and festive moments are highly associated. A control group that did not participate in the prevention program was asked the same questions over the same number of days for the first 2 periods. During the second period, the participants were asked to answer questions about their alcohol consumption during parties. During the third period, we explored the interaction with the prevention program on the reduction of their belief that alcohol consumption and festive moments are associated. RESULTS: A total of 651 participants (age: mean 22.24, SD 4.10 years; women: n=430) during the first period, 301 participants (age: mean 21.27, SD 3.07 years; women n=199) during the second period, and 305 (age: mean 22.41, SD 4.65 years; women: n=190) during the third period correctly completed the survey. For the control group, 69 students completed the survey during the first period (age: mean 18.93, SD 1.14 years; women: n=59) and 50 during the second (age: mean 20.78, SD 1.94 years; women: n=45). We observed a significant reduction in the association of alcohol with festive moments in the participants over the 2 years (period 1: z=-4.80, P<.001; period 2: z=-2.11, P=.04; period 3: z=-2.30; P=.02), but not in the controls. We also observed a reduction in the number of glasses consumed during festive moments for the participants (z=-2.36, P=.02), but not for the controls during the second period. The third period showed that only the number of days since registration in the program had an impact on the reduction of the association of festive moments and alcohol consumption (t21=3.186, P=.005). CONCLUSIONS: The findings of this study suggest that the SNS prevention program is promising in preventing the association of alcohol with festive moments and, more generally, in impacting social norms. PMID- 26681578 TI - Covert orienting in the split brain: Right hemisphere specialization for object based attention. AB - The present paper takes as its starting point Phil Bryden's long-standing interest in human attention and the role it can play in laterality effects. Past split-brain research has suggested that object-based attention is lateralized to the left hemisphere [e.g., Egly, R., Rafal, R. D., Driver, J., & Starreveld, Y. (1994). Covert orienting in the split brain reveals hemispheric specialization for object-based attention. Psychological Science, 5(6), 380-382]. The task used to isolate object-based attention in that previous work, however, has been found wanting [Vecera, S. P. (1994). Grouped locations and object-based attention: Comment on Egly, Driver, and Rafal (1994). Journal of Experimental Psychology: General, 123(3), 316-320]; and indeed, subsequent research with healthy participants using a different task has suggested that object-based attention is lateralized to the opposite right hemisphere (RH) [Valsangkar-Smyth, M. A., Donovan, C. L., Sinnett, S., Dawson, M. R., & Kingstone, A. (2004). Hemispheric performance in object-based attention. Psychonomic Bulletin & Review, 11(1), 84 91]. The present study tested the same split-brain as Egly, Rafal, et al. (1994) but used the object-based attention task introduced by Valsangkar-Smyth et al. (2004). The results confirm that object-based attention is lateralized to the RH. They also suggest that subcortical interhemispheric competition may occur and be dominated by the RH. PMID- 26681579 TI - Corrigendum: Magmatic record of India-Asia collision. PMID- 26681580 TI - Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice. AB - Respiratory syncytial virus (RSV) causes severe bronchiolitis in infants worldwide. The immunological factors responsible for RSV susceptibility in infants are poorly understood. Here, we used the BALB/c mouse model of neonatal RSV infection to study the mechanisms leading to severe disease upon reexposure to the virus when adults. Two major deficiencies in neonatal lung innate responses were found: a poor DCs mobilization, and a weak engagement of the IFNI pathway. The administration of Flt3 ligand (Flt3-L), a growth factor that stimulates the proliferation of hematopoietic cells, to neonates before RSV infection, resulted in increased lung DC number, and reconditioned the IFNI pathway upon RSV neonatal infection. Besides, neonates treated with Flt3-L were protected against exacerbated airway disease upon adult reexposure to RSV. This was associated with a reorientation of RSV-specific responses toward Th1-mediated immunity. Thus, the poor lung DCs and IFNI responses to RSV in neonates may be partly responsible for the deleterious long-term consequences revealed upon adult reexposure to RSV, which could be prevented by Flt3-L treatment. These results open new perspectives for developing neonatal immuno-modulating strategies to reduce the burden of bronchiolitis. PMID- 26681581 TI - The effect of in vivo resveratrol supplementation in irradiated mice on the induction of micronuclei in peripheral blood and bone marrow reticulocytes. AB - The aim of the study was to investigate how coadministration of resveratrol (RSV) at different time after the start of irradiation influences the frequency of micronuclei (MN) in reticulocytes of bone marrow and peripheral blood, and if the RSV supplementation after termination of irradiation may influence the recovery process of damaged cells. Coadministration of RSV with 1-day delay after 1 Gy irradiation significantly decreased the levels of MN in bone marrow and in peripheral blood, whereas with 1-week delay, only in bone marrow reticulocytes. Above combined treatment did not improve the process of recovery. RSV supplementation with 1-day delay relatively to 0.5 Gy irradiation, significantly decreased the frequencies of MN, especially after coadministration with 28mg/kg bw of RSV. Coadministration of RSV since eighth day did not influence the frequencies of MN compared to irradiated cells. The recovery process in the presence of RSV proceeded faster. Supplementation of RSV following initiation of irradiation is beneficial in case of irradiation with lower doses. RSV should be supplemented as soon as possible. Supplementation of RSV after termination of irradiation significantly speed up the recovery. Current results confirmed the ability of RSV to mitigate the effect of irradiation. PMID- 26681582 TI - Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin-4 overexpression in colorectal cancer. AB - Galectin-4 is a member of the galectin family which consists of 15 galactoside binding proteins. Previously, galectin-4 has been shown to have a role in cancer progression and metastasis and it is found upregulated in many solid tumours, including colorectal cancer (CRC). Recently, the role in the metastatic process was suggested to be via promoting cancer cells to adhere to blood vascular endothelium. In the present study, the regulatory region of LGALS4 (galectin-4) in seven colon cell lines was investigated with respect to genetic variation that could be linked to expression levels and therefore a tumourigenic effect. Interestingly, qRT-PCR and sequencing results revealed that galectin-4 upregulation is associated with SNPs rs116896264 and rs73933062. By use of luciferase reporter- and pull-down assays, we confirmed the association between the gene upregulation and the two SNPs. Also, using pull-down assay followed by mass spectrometry, we found that the presence rs116896264 and rs73933062 is changing transcription factors binding sites. In order to assess the frequencies of the two SNPs among colon cancer patients and healthy individuals, we genotyped 75 colon cancer patients, 12 patients with adenomatous polyposis and 17 patients with ulcerative colitis and we performed data mining in the 1000 genomes databank. We found the two SNPs co-occuring in 21% of 75 CRC patients, 0 out of 12 patients of adenomatous polyposis, and 6 out of 17 patients (35%) with ulcerative colitis. Both in the patient samples and in the 1000 genomes project, the two SNPs were found to co-occur whenever present (D' = 1). PMID- 26681583 TI - Clinical Response, Outbreak Investigation, and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review. AB - We conducted a systematic review of the 2012-2013 multistate fungal meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the fungal meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the fungal meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health. PMID- 26681585 TI - Extreme light. PMID- 26681584 TI - Archaeal and bacterial communities across a chronosequence of drained lake basins in Arctic Alaska. AB - We examined patterns in soil microbial community composition across a successional gradient of drained lake basins in the Arctic Coastal Plain. Analysis of 16S rRNA gene sequences revealed that methanogens closely related to Candidatus 'Methanoflorens stordalenmirensis' were the dominant archaea, comprising >50% of the total archaea at most sites, with particularly high levels in the oldest basins and in the top 57 cm of soil (active and transition layers). Bacterial community composition was more diverse, with lineages from OP11, Actinobacteria, Bacteroidetes, and Proteobacteria found in high relative abundance across all sites. Notably, microbial composition appeared to converge in the active layer, but transition and permafrost layer communities across the sites were significantly different to one another. Microbial biomass using fatty acid-based analysis indicated that the youngest basins had increased abundances of gram-positive bacteria and saprotrophic fungi at higher soil organic carbon levels, while the oldest basins displayed an increase in only the gram-positive bacteria. While this study showed differences in microbial populations across the sites relevant to basin age, the dominance of Candidatus 'M. stordalenmirensis' across the chronosequence indicates the potential for changes in local carbon cycling, depending on how these methanogens and associated microbial communities respond to warming temperatures. PMID- 26681591 TI - Weyl semimetals: A group family picture. PMID- 26681592 TI - Zeolites: A synthetic solution. PMID- 26681593 TI - Material Witness: Spinning top-ology. PMID- 26681594 TI - Liquid crystals: Material defect lines. PMID- 26681595 TI - Correction. PMID- 26681598 TI - Fatigue strength of bilayered ceramics under cyclic loading as a function of core veneer thickness ratios. AB - STATEMENT OF PROBLEM: Minimal evidence is available concerning the appropriate thickness of each layer in bilayered ceramic systems. PURPOSE: The purpose of this in vitro study was to examine the effect of core-veneer thickness ratios on the fatigue strength of a bonded bilayered ceramic system. MATERIAL AND METHODS: Specimens of Ivoclar Porcelain System (IPS) e.max lithium disilicate were fabricated with core/veneer thicknesses of 0.5/1.0 mm, 0.75/0.75 mm, 1.0/0.5 mm, and 1.5/0.0 mm. All specimens were cemented to bases of a dentin-like material. Each specimen was cyclically loaded by a 2-mm-diameter G10 piston in water. Loads ranging from 10 N to the target load were applied at a frequency of 20 Hertz for 500,000 cycles. If cracked, the next specimen was cycled at a lower load; if not cracked, at a higher load (step size of 25 N). RESULTS: Mean and standard deviations of fatigue loads for the different core thicknesses were 0.5-mm core 610.94 N +/-130.11; 0.75-mm core 600.0 N +/-132.80; 1.0-mm core 537.50 N +/ 41.67; a Nd 1.5-mm core 501.14 N +/-70.12. All veneered groups were significantly stronger than the full thickness group (ANOVA, P<.001; 95% post hoc). Cone cracking was observed only in the 2 thinner core groups (chi(2) test, P<.05), possibly indicating residual stresses. CONCLUSIONS: Results indicate that the addition of veneering porcelain to lithium disilicate cores increases the fatigue strength of the biceramic system. PMID- 26681597 TI - Functional characterization of NADPH-cytochrome P450 reductase from Bactrocera dorsalis: Possible involvement in susceptibility to malathion. AB - NADPH cytochrome P450 reductase (CPR) is essential for cytochrome P450 catalysis, which is important in the detoxification and activation of xenobiotics. In this study, two transcripts of Bactrocera dorsalis CPR (BdCPR) were cloned, and the deduced amino-acid sequence had an N-terminus membrane anchor for BdCPR-X1 and three conserved binding domains (FMN, FAD, and NADP), as well as an FAD binding motif and catalytic residues for both BdCPR-X1 and BdCPR-X2. BdCPR-X1 was detected to have the high expression levels in adults and in Malpighian tubules, fat bodies, and midguts of adults, but BdCPR-X2 expressed lowly in B. dorsalis. The levels of BdCPRs were similar in malathion-resistant strain compared to susceptible strain. However, injecting adults with double-stranded RNA against BdCPR significantly reduced the transcript levels of the mRNA, and knockdown of BdCPR increased adult susceptibility to malathion. Expressing complete BdCPR-X1 cDNA in Sf9 cells resulted in high activity determined by cytochrome c reduction and these cells had higher viability after exposure to malathion than control. The results suggest that BdCPR could affect the susceptibility of B. dorsalis to malathion and eukaryotic expression of BdCPR would lay a solid foundation for further investigation of P450 in B. dorsalis. PMID- 26681602 TI - The complete mitochondrial genome of the green-backed tit Parus monticolus (Passeriformes: Paridae). AB - The complete mitochondrial genome of the green-backed tit Parus monticolus was assembled from Illumina sequencing reads. The genome is 16 771 bp long, and harbors 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), and one control region. All PCGs are initiated with the ATG codon except for COX1 with GTG as its start codon. Five distinct types of stop codons are inferred, i.e. AGA (ND1 and ND5), AGG (COX1), TAA (ATP6, ATP8, COX2, ND3 and ND4L), TAG (ND6), and the incomplete codon T/TA (COX3, CYTB, ND2 and ND4). The 22 tRNAs range in size from 66 to 75 bp. The 12S and 16S rRNAs are 982 and 1601 bp long, respectively, and are separated by tRNA-Val gene. The putative control region is located between tRNA-Glu and tRNA-Phe with a length of 1187 bp. Phylogenetic analysis indicated that this species is closely related to its congener P. major. PMID- 26681599 TI - From an imbalance to a new imbalance: Italian-style gluten-free diet alters the salivary microbiota and metabolome of African celiac children. AB - Fourteen Saharawi celiac children following an African-style gluten-free diet for at least two years were subjected to a change of diet to an Italian-style gluten free diet for 60 days. Significant differences were identified in the salivary microbiota and metabolome when Saharawi celiac children switched from African- to Italian-style dietary habits. An Italian-style gluten-free diet caused increases in the abundance of Granulicatella, Porphyromonas and Neisseria and decreases in Clostridium, Prevotella and Veillonella, altering the 'salivary type' of the individuals. Furthermore, operational taxonomic unit co-occurrence/exclusion patterns indicated that the initial equilibrium of co-occurring microbial species was perturbed by a change in diet: the microbial diversity was reduced, with a few species out-competing the previously established microbiota and becoming dominant. Analysis of predicted metagenomes revealed a remarkable change in the metabolic potential of the microbiota following the diet change, with increased potential for amino acid, vitamin and co-factor metabolism. High concentrations of acetone and 2-butanone during treatment with the Italian-style gluten-free diet suggested metabolic dysfunction in the Saharawi celiac children. The findings of this study support the need for a translational medicine pipeline to examine interactions between food and microbiota when evaluating human development, nutritional needs and the impact and consequences of westernisation. PMID- 26681603 TI - Imagery rescripting of revenge, avoidance, and forgiveness for past bullying experiences in young adults. AB - BACKGROUND AND OBJECTIVES: Forgiveness has been found to be a useful intervention for past trauma across a variety of situations. However, this has yet to be experimentally tested in victims of bullying. The aim of the current study was to evaluate the impact of imagining forgiveness, avoidance, or revenge responses towards a perpetrator among young adult victims of bullying. METHODS: One hundred and thirty-five undergraduate psychology students aged 17-24 who reported a recent experience of being victimized were led through imagery rescripting where they recalled a personal episode of bullying and imagined a new ending to one where they forgave, avoided, or took revenge on the bully. RESULTS: Results indicated significant differences between Time 1 (imagining the event as it occurred), to Time 2 (imagining an alternate ending) for all three processes. Negative affect decreased significantly in the forgiveness and avoidance conditions, but not in the revenge condition. Positive evaluations of coping decreased significantly in the revenge condition, but not in the avoidance or forgiveness conditions. However, imagined forgiveness of the bully was more stressful than either imagined avoidance or revenge. LIMITATIONS: The short-term measurements and the researcher-directed re-scripting limit the interpretation of results, however, yield valuable information about the immediate impact of imaginal exposure and point to future research directions. CONCLUSIONS: The impact of focusing on immediate stress reduction in dealing with bullying is explored, and a combination of short-term avoidance and longer term forgiveness is highlighted as a potentially effective strategy to deal with the negative emotional consequences of victimization. PMID- 26681596 TI - Supramolecular biomaterials. AB - Polymers, ceramics and metals have historically dominated the application of materials in medicine. Yet rationally designed materials that exploit specific, directional, tunable and reversible non-covalent interactions offer unprecedented advantages: they enable modular and generalizable platforms with tunable mechanical, chemical and biological properties. Indeed, the reversible nature of supramolecular interactions gives rise to biomaterials that can sense and respond to physiological cues, or that mimic the structural and functional aspects of biological signalling. In this Review, we discuss the properties of several supramolecular biomaterials, as well as their applications in drug delivery, tissue engineering, regenerative medicine and immunology. We envision that supramolecular biomaterials will contribute to the development of new therapies that combine highly functional materials with unmatched patient- and application specific tailoring of both material and biological properties. PMID- 26681604 TI - Health Coaching the Worker With Celiac Disease. AB - L.Y., a 52-year-old project manager, had a series of minor epistaxis episodes while at work. After seeing his primary care physician, he was diagnosed with anemia which was attributed to the epistaxis. After being evaluated by an ear, nose, and throat (ENT) specialist for treatment of the epistaxis, anemia continued. Eventually, he was diagnosed with celiac disease. Implications for health coaching are explored. PMID- 26681605 TI - Impact of Work Environments and Occupational Hazards on Smoking Intensity in Korean Workers. AB - The purpose of this study was to investigate the influence of work environments and occupational hazards on smoking intensity by occupation type in Korean workers. This study used the data from the Fourth Korea National Health and Nutrition Examination Survey in 2009. The sample of this study included 3,769 adults who were aged 18 years or older and had an occupation of office work, sales, or manufacturing. After controlling for sociodemographic characteristics, the generalized linear models revealed that office workers and the sales force who had smoking co-workers at the workplace were more likely to smoke than those who did not. A dirty workplace and exposure to occupational noise were significant factors increasing the smoking intensity for manufacturers. A smoking cessation program considering physical work environments and co-workers' support should be developed for Korean workers. PMID- 26681606 TI - The most important global public health agreement of the century. PMID- 26681607 TI - Condensing Raman spectrum for single-cell phenotype analysis. AB - BACKGROUND: In recent years, high throughput and non-invasive Raman spectrometry technique has matured as an effective approach to identification of individual cells by species, even in complex, mixed populations. Raman profiling is an appealing optical microscopic method to achieve this. To fully utilize Raman proling for single-cell analysis, an extensive understanding of Raman spectra is necessary to answer questions such as which filtering methodologies are effective for pre-processing of Raman spectra, what strains can be distinguished by Raman spectra, and what features serve best as Raman-based biomarkers for single-cells, etc. RESULTS: In this work, we have proposed an approach called rDisc to discretize the original Raman spectrum into only a few (usually less than 20) representative peaks (Raman shifts). The approach has advantages in removing noises, and condensing the original spectrum. In particular, effective signal processing procedures were designed to eliminate noise, utilising wavelet transform denoising, baseline correction, and signal normalization. In the discretizing process, representative peaks were selected to signicantly decrease the Raman data size. More importantly, the selected peaks are chosen as suitable to serve as key biological markers to differentiate species and other cellular features. Additionally, the classication performance of discretized spectra was found to be comparable to full spectrum having more than 1000 Raman shifts. Overall, the discretized spectrum needs about 5storage space of a full spectrum and the processing speed is considerably faster. This makes rDisc clearly superior to other methods for single-cell classication. PMID- 26681608 TI - German ablation registry: Cryoballoon vs. radiofrequency ablation in paroxysmal atrial fibrillation--One-year outcome data. AB - BACKGROUND: Although radiofrequency (RF) ablation has long been the standard of care for atrial fibrillation (AF) ablation, cryoballoon technology has emerged as a feasible approach with promising results. Prospective multicenter registry data referring to both ablation technologies in AF ablation are lacking so far. OBJECTIVE: The purpose of this study was to report data from the German ablation registry with respect to efficacy and safety in pulmonary vein ablation with different energy sources for paroxysmal AF after 1-year follow-up. METHODS: A total of 2306 patients with symptomatic paroxysmal AF from the German ablation registry were included in this analysis. The cohort was divided into two groups according to the ablation energy source used: cryoballoon and RF ablation. MACCE was defined as a combination of death, myocardial infarction, or stroke. RESULTS: AF recurrence rate after a single ablation procedure at 1 year follow-up was not significantly different between the two groups (45.8% after cryoablation and 45.4% after RF ablation, P = .87). Also, the rate of patients without AF recurrence and free of antiarrhythmic drug at 12-month follow-up was similar (cryoablation 44.2% and RF 41.4%, P = .25). MACCE occurred with an incidence of 0.7% within 500 days after cryoablation and 1.4% after RF ablation (P = .30). Persistent phrenic nerve palsy was more common after cryoablation compared to RF ablation (1.1% vs. 0.3%, P <.05). CONCLUSION: AF recurrence rate at 1-year follow up was similar in RF ablation compared to cryoablation, whereas the spectrum and relevance of complications were significantly different between the two ablation methods. This finding might influence the choice of ablation method offered to the individual paroxysmal AF patient. PMID- 26681609 TI - Detailed characterization of familial idiopathic ventricular fibrillation linked to the DPP6 locus. AB - BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and is notoriously difficult to manage because there are no clinical risk indicators for premature cardiac arrest. Previously, we identified a link between familial IVF and a risk haplotype on chromosome 7q36 (involving the arrhythmia gene DPP6). OBJECTIVE: The purpose of this study was to expand our knowledge of familial IVF and to discuss its (extended) clinical characteristics. METHODS: We studied 601 family members and probands: 286 DPP6 risk-haplotype positive (haplotype-positive) and 315 DPP6 risk-haplotype negative (haplotype negative) individuals. Clinical parameters, a combination of all-cause mortality and (aborted) cardiac arrest and differences between haplotype-positives and haplotype-negatives, were evaluated. RESULTS: There were no differences in electrocardiographic indices between haplotype-positives and haplotype-negatives, or between haplotype-positives with or without events. Cardiac magnetic resonance documented slightly larger ventricular volumes in haplotype-positives compared to controls (P <.05), but these were not clinically useful. Mortality and/or cardiac arrest occurred in 85 haplotype-positives (30%) and 18 haplotype-negatives (6%). Twenty-four haplotype-positives (8% male) were resuscitated from ventricular fibrillation (VF). Documented VF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall. Median survival in risk-haplotype haplotype-positives was 70 vs. 93 years for haplotype-negatives (P < .01), with a worse phenotype in males (median survival 63 vs. 83 years in females, P < .01). Implantable cardioverter-defibrillators were implanted in 99 patients (76 [77%] for primary prevention). Two arrhythmic events occurred in the primary prevention group during follow-up (5 +/- 3 years). CONCLUSION: Despite our extensive analysis, the complexity in identifying asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated. PMID- 26681610 TI - Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness. AB - BACKGROUND: Vernakalant inhibits several potassium currents and causes a rate- and voltage-dependent inhibition of the sodium current. OBJECTIVE: The aim of this study was to evaluate the antiarrhythmic mechanism of vernakalant in normal and electrically remodeled atria. METHODS: Fourteen goats were instrumented with electrodes on both atria. Drug effects on refractory period (ERP), conduction velocity (CV), and atrial fibrillation cycle length (AFCL) were determined in normal goats (control) and after 2 (2dAF) or 11 (11dAF) days of pacing-induced atrial fibrillation (AF) in awake goats. To evaluate the contribution of changes in conduction and ERP, the same experiments were performed with flecainide and AVE0118. In a subset of goats, monophasic action potentials were recorded during anesthesia. RESULTS: Vernakalant dose-dependently prolonged ERP and decreased CV in CTL experiments. Both effects were maintained after 2dAF and 11dAF. After 11dAF, conduction slowed down by 8.2 +/- 1.5 cm/s and AFCL increased by 55 +/- 3 ms, leading to AF termination in 5 out of 9 goats. Monophasic action potential measurements revealed that ERP prolongation was due to enhanced postrepolarization refractoriness. During pacing, vernakalant had comparable effects on CV as flecainide, while effect on ERP was comparable to AVE0118. During AF, all compounds had comparable effects on median AFCL and ERP despite differences in their effects on CV during pacing. CONCLUSION: The antiarrhythmic effect of vernakalant in the goat, at clinically relevant plasma concentrations, is based on both conduction slowing and ERP prolongation due to postrepolarization refractoriness. These electrophysiological effects were not affected by long-term electrical remodeling of the atria. PMID- 26681611 TI - Implantable cardioverter-defibrillator explantation for overdiagnosed or overtreated congenital long QT syndrome. AB - BACKGROUND: Primary treatment of long QT syndrome (LQTS) currently consists of beta-blocker therapy, although an implantable cardioverter-defibrillator (ICD) is considered for high-risk patients. However, both overdiagnosis and overtreatment must be avoided because their sequelae can be significant. OBJECTIVE: The purpose of this study was to evaluate the prevalence and details of ICD explants in a cohort of patients from a tertiary genetic heart rhythm clinic for a previously rendered diagnosis of LQTS. METHODS: Overall, 1227 consecutive patients were included in the study. All patients had been referred to the Mayo Clinic for evaluation of possible LQTS and subsequently were either diagnosed with LQTS or dismissed as normal. Further stratification of patients was conducted to assess how many patients had an ICD and how many had a subsequent ICD explant. RESULTS: In total, 170 patients (14%) had an ICD, including 157 of 670 patients (23%) with confirmed LQTS and 13 of 557 patients (2%) who did not have LQTS. Among these, 12 of 1227 (1%) had the ICD removed: 7 of 157 LQTS patients (4.5%) compared to 5 of 14 non-LQTS patients (36%). Before explant, 5 of 12 patients (42%) experienced inappropriate shocks, ranging from 2 to as many as 54 shocks. In addition, 4 had a device-related infection, and 9 had device malfunction (including lead dysfunction or fracture). None of these patients had a breakthrough cardiac event since removal of their ICD during 5.5 +/- 3.5 years of follow-up. CONCLUSION: Implications of overdiagnosis and overtreatment are profound because unnecessary ICD placement can be associated with infection, malfunction, inappropriate shocks, and subsequent anxiety. PMID- 26681612 TI - Diversity and representation: Key issues for psychophysiological science. AB - This Special Issue is devoted to the illustration and discussion of three key demographic variables (sex/gender, race/ethnicity, and socioeconomic status) that have been shown to moderate associations between psychophysiological processes and behavior. The introduction to the issue discusses the role of phenotypic plasticity in the emergence of different neural processes that achieve the same behavioral outcome, with emphasis on how these relatively stable developmental contexts affect brain/behavior associations without necessarily resulting in difference in behavior. These findings have profound significance for the implications of generalization and call into question the presumption that diverse samples produce an average result that is appropriately reflective of the individuals themselves. Increasing diversity within psychophysiological research is critical in elucidating mechanisms by which the human brain can accomplish cognitive and affective behaviors. This article further examines the logistical and ethical challenges faced in achieving this goal. PMID- 26681613 TI - Neurological damage disrupts normal sex differences in psychophysiological responsiveness to music. AB - Men and women often display different physiological responses to emotional stimuli, and these responses can be affected by brain damage. Here, we investigated how brain damage differentially affects electrodermal responses based on sex. We studied neurologically normal, healthy adults and a sample of neurological patients. Participants listened to music, an emotional stimulus that reliably elicits skin conductance responses (SCRs). Electrodermal activity was recorded while participants listened to musical clips. When analyzing the data without regard to sex, there were no differences between healthy and brain damaged participants in their SCRs. However, we found a significant interaction between brain injury status and sex. For men, brain damage significantly reduced SCRs. For women, there were no differences between brain-damaged participants and neurologically healthy participants. These findings illustrate the importance of including demographic variables, such as sex, when investigating brain-behavior relationships with a psychophysiological dependent variable. PMID- 26681614 TI - Sex moderates the association between symptoms of anxiety, but not obsessive compulsive disorder, and error-monitoring brain activity: A meta-analytic review. AB - Sex differences in cognition and emotion are particularly active areas of research. Much of this work, however, focuses on mean-level differences between the sexes on cognitive and/or emotional variables in isolation. In this article, we are primarily concerned with how sex affects associations between cognition and emotion, or cognition-emotion interactions. Specifically, the purpose of this paper is to shed light on a gap in our understanding of how sex affects the relationship between error monitoring, a core component of cognitive control, and anxiety. Using meta-analysis, we show that the relationship between symptoms of anxiety and a neurophysiological marker of error monitoring-the error-related negativity (ERN)-is significantly greater in women than men such that women, but not men, with higher levels of anxiety show a larger ERN. This sex difference held true across studies of anxiety-specific symptoms but not studies of obsessive-compulsive symptoms. These findings underscore the need to consider sex in studies of anxiety and the ERN as well as support growing evidence indicating that obsessive-compulsive problems are distinguishable from other anxiety specific problems across multiple levels of analysis. Overall, we conclude that ignoring sex in studies of cognition-emotion interactions is unacceptable. Rather, future research that continues to tackle questions related to sex differences in associations between cognition and emotion will more likely lead to advancements in basic and applied sciences of relevance to health and human behavior. PMID- 26681615 TI - To Stroop or not to Stroop: Sex-related differences in brain-behavior associations during early childhood. AB - Executive functions (EFs) are linked with optimal cognitive and social-emotional development. Despite behavioral evidence of sex differences in early childhood EF, little is known about potential sex differences in corresponding brain behavior associations. The present study examined changes in 4-year-olds' 6-9 Hz EEG power in response to increased executive processing demands (i.e., "Stroop like" vs. "non-Stroop" day-night tasks). Although there were no sex differences in task performance, an examination of multiple scalp electrode sites revealed that boys exhibited more widespread changes in EEG power as compared to girls. Further, multiple regression analyses controlling for maternal education and non EF performance indicated that individual differences in boys' and girls' EF performance were associated with different frontal neural correlates (i.e., different frontal scalp sites and different measures of EEG power). These data reveal valuable information concerning sex differences in the neural systems underlying executive processing during early childhood. PMID- 26681616 TI - Convergence in feeling, divergence in physiology: How culture influences the consequences of disgust suppression and amplification among European Americans and Asian Americans. AB - Much empirical work documents the downsides of suppressing emotions. Emerging research points to the need for a more sophisticated and culturally informed approach to understanding the consequences of emotion regulation. To that end, we employed behavioral, self-report, and psychophysiological measures to examine the consequences of two types of emotion regulation (suppression and amplification) in a sample of 28 Asian Americans and 31 European Americans. Participants were shown a neutral film and then a series of disgust-eliciting films during which they were asked to regulate their response by suppressing or amplifying their emotional behavior (counterbalanced). Despite self-reporting equal levels of disgust, European Americans showed greater skin conductance reactivity than Asian Americans in both regulation conditions, but not in response to a neutral film. These findings extend work on divergence in the consequences of emotion regulation across different cultural groups, which could help identify optimal emotion regulation strategies for health and well-being. PMID- 26681617 TI - Cultural shaping of neural responses: Feedback-related potentials vary with self construal and face priming. AB - Previous work shows that when an image of a face is presented immediately prior to each trial of a speeded cognitive task (face-priming), the error-related negativity (ERN) is upregulated for Asians, but it is downregulated for Caucasians. These findings are consistent with the hypothesis that images of "generalized other" vary cross-culturally such that they evoke anxiety for Asians, whereas they serve as safety cues for Caucasians. Here, we tested whether the cross-cultural variation in the face-priming effect would be observed in a gambling paradigm. Caucasian Americans, Asian Americans, and Asian sojourners were exposed to a brief flash of a schematic face during a gamble. For Asian Americans, face-priming resulted in significant increases of both negative-going deflection of ERP upon negative feedback (feedback-related negativity [FRN]) and positive-going deflection of ERP upon positive feedback (feedback-related positivity [FRP]). For Caucasian Americans, face-priming showed a significant reversal, decreasing both FRN and FRP. The cultural difference in the face priming effect in FRN and FRP was partially mediated by interdependent self construal. Curiously, Asian sojourners showed a pattern similar to the one for Caucasian Americans. Our findings suggest that culture shapes neural pathways in both systematic and highly dynamic fashion. PMID- 26681618 TI - Ethnic/racial differences in the association between social support and levels of C-reactive proteins in the North Texas Heart Study. AB - Perceived social support has been reliably related to lower rates of morbidity and mortality. However, studies modeling C-reactive protein (CRP) as an important biological pathway linking social support to health have produced inconsistent results. Given purported ethnic/racial differences in sensitivity to social resources, the present study tested if ethnicity/race moderated the link between perceived support and CRP in a diverse community sample of 300 participants from the North Texas Heart Study. Consistent with prior research, there was no overall link between social support and CRP levels. However, the association between social support and high sensitivity (hs)-CRP levels was moderated by ethnicity/race as perceived support predicted lower hs-CRP levels primarily in African Americans. These results suggest the importance of considering how ethnicity/race may inform models on the complex biological mechanisms linking social support to health. PMID- 26681619 TI - Neurocognitive development in socioeconomic context: Multiple mechanisms and implications for measuring socioeconomic status. AB - Socioeconomic status (SES) has been linked to functioning across a variety of neurocognitive domains including language, memory, executive functioning, and social-emotional processing. We review these findings and discuss the ways in which socioeconomic context may shape neural processes such that these skills are supported by different neurobiological pathways in children from lower versus higher SES backgrounds. Moreover, we consider the mechanisms by which SES may be related to specific neurocognitive functions. Specifically, we focus on linguistic exposure and stress as two main pathways through which SES could influence neurocognitive processes and shape relations between the neural and behavioral levels of functioning. Finally, suggestions for conceptualizing and measuring SES in future work are offered. PMID- 26681622 TI - Threatening the heart and mind of gender stereotypes: Can imagined contact influence the physiology of stereotype threat? AB - Research shows that when a gender stereotype is made salient and the target of the stereotype is asked to perform in the stereotyped domain, targets of the stereotype often perform at a lower level compared to situations when the stereotype was not made salient. The noticeable absence of female faculty and students in math and science departments at coed universities throughout the United States may increase the belief in gender stereotypes and discourage women from pursuing careers in these fields. Contact with counterstereotypical exemplars, such as female science experts, decreases belief in gender stereotypes and increases women's motivation to pursue careers in science. Thus, the present study examined whether imagining an interpersonal interaction with a counterstereotypical exemplar removes the physiological and performance effects of stereotype threat. Subjects were asked to imagine either a nature scene or meeting a female math professor, and were also assigned to either a control or stereotype threat condition. Imagination was used because studies have shown it to be an effective method of simulating interpersonal contact. Subjects were 139 young women (mean age 19 years) recruited from a pool of undergraduates. Results showed that the stereotype threat manipulation elicited greater vagal withdrawal and poorer working memory capacity during the n-back, and that vagal withdrawal was attenuated when the stereotype threat manipulation was preceded by a brief imagined interaction with a counterstereotypical exemplar. This study provides novel evidence that exposure to counterstereotypical exemplars can diminish cardiovascular reactions to salient information about threatening gender stereotypes. PMID- 26681620 TI - Early caregiving stress exposure moderates the relation between respiratory sinus arrhythmia reactivity at 1 month and biobehavioral outcomes at age 3. AB - There is a growing scientific interest in the psychophysiological functioning of children living in low-socioeconomic status (SES) contexts, though this research is complicated by knowledge that physiology-behavior relations often operate differently in these environments among adults. Importantly, such research is made more difficult because SES may be a proxy for a wide range of risk factors including poor caregiving and exposure to parental substance use. We used factor analysis to organize risk-exposure data collected from 827 children-many of whom were raised in low-SES contexts and exposed to substances prenatally-into dissociable components including economic stress, caregiving stress (e.g., stress the caregiver may experience, including parental psychopathology), and postnatal substance exposure. These factors, along with respiratory sinus arrhythmia (RSA) reactivity at age 1 month, were used to predict behavior dysregulation and resting RSA at age 3 years. A significant RSA Reactivity * Caregiving Stress interaction indicated that infants who exhibited high RSA reactivity at 1 month experienced the greatest behavior dysregulation at 3 years, but only when they were exposed to high levels of caregiving stress. Among African Americans, the highest resting RSA at 3 years was found in infants with less RSA reactivity, but only if they also experienced less caregiving stress. Our work is consistent with biological sensitivity to context, adaptive calibration, and allostatic load models, and highlights the importance of studying Physiology * Environment interactions in low-SES contexts for predicting behavior and resting RSA. PMID- 26681623 TI - Emotional Perception of Music in Children With Bimodal Fitting and Unilateral Cochlear Implant. AB - OBJECTIVE: Biological, structural, and acoustical constraints faced by cochlear implant (CI) users can alter the perception of music. Bimodal fitting not only provides bilateral hearing but can also improve auditory skills. This study was conducted to assess the impact of this amplification style on the emotional perception of music among children with hearing loss (HL). METHODS: Twenty-five children with congenital severe to profound HL and unilateral CIs, 20 children with bimodal fitting, and 30 children with normal hearing participated in this study. Their emotional perceptions of music were measured using a method where children indicated happy or sad feelings induced by music by pointing to pictures of faces showing these emotions. RESULTS: Children with bimodal fitting obtained significantly higher mean scores than children with unilateral CIs for both happy and sad music items and in overall test scores (P < .001). Both groups with HL obtained significantly lower scores than children with normal hearing (P < .001). CONCLUSIONS: Bimodal fitting results in a better emotional perception of music compared to unilateral CI. Given the influence of music in neurological and linguistic development and social interactions, it is important to evaluate the possible benefits of bimodal fitting prescriptions for individuals with unilateral CIs. PMID- 26681621 TI - The impact of maternal depression and overcrowded housing on associations between autonomic nervous system reactivity and externalizing behavior problems in vulnerable Latino children. AB - The study of autonomic nervous system responses and contextual factors has shed light on the development of children's negative outcomes, but the majority of these studies have not focused on minority populations living under adversity. To address these gaps, the current longitudinal study included a sample of poor, immigrant Latino families to examine whether associations between children's autonomic nervous system reactivity at 6 months and their externalizing behavior problems at 7 years of age were moderated by two risk factors associated with poverty: the interpersonal factor of chronic maternal depression and the environmental factor of chronic overcrowded housing. Multiple linear regression (N = 99) revealed that children who exhibited less parasympathetic nervous system withdrawal in response to challenge during infancy had more externalizing problems during childhood only if they had mothers who experienced chronic depression. Children who exhibited greater sympathetic nervous system reactivity during infancy had the lowest levels of externalizing problems during childhood only if they had mothers who chronic depression. Chronic overcrowded housing did not moderate associations between physiological reactivity and level of externalizing problems. These findings extend our understanding of the interaction of physiology and context on child outcomes to the understudied population of impoverished Latino families. PMID- 26681624 TI - Mast Cell Deficiency Limits the Development of Chronic Rhinosinusitis in Mice. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in adults in both developing and developed countries. The etiology and pathogenesis of CRS remain poorly understood, and the disease is refractory to therapy in many patients. Mast cell activation has been demonstrated in the sinonasal mucosa of patients with CRS; however, the specific contribution of mast cells to the development and pathogenesis of this disease has not been established. OBJECTIVE: The objective of this study was to investigate the role of mast cells in the development of CRS. METHODS: C57BL/6 wild-type and C57BL/6 Kit(W-sh/W-sh) mast cell-deficient mice were immunized by intraperitoneal allergen injection and subsequent chronic low dose intranasal allergen challenges. The sinonasal phenotypes of these groups were then evaluated and compared to saline-treated controls using radiologic, histologic, and immunologic methods. RESULTS: Wild-type mice exposed to chronic intranasal allergen developed many features seen in human CRS, including mucosal thickening, cystic changes, polyp development, eosinophilia, goblet cell hyperplasia, and mast cell activation. In contrast, sinonasal pathology was significantly attenuated in mast cell-deficient mice subjected to the same chronic allergen protocol. Specifically, tissue eosinophilia and goblet cell hyperplasia were reduced by approximately 50% compared to wild-type levels. Surprisingly, none of the mast cell-deficient mice subjected to chronic allergen challenge developed cystic changes or polypoid changes in the nose or sinuses. CONCLUSIONS: These data identify a critical role for mast cells in the development of many features of a mouse model of eosinophilic CRS, suggesting that therapeutic strategies targeting mast cells be examined in humans afflicted with this disease. PMID- 26681625 TI - Autonomic nervous activity of patients with gagging problems during dental mirror insertion. AB - OBJECTIVE: To investigate autonomic nervous activities in patients with gagging problem. METHODS: Subjects were 12 and 12 individuals, graded as Group G2 (mild gagging problem) and Group G3 (middle gagging problem), respectively, according to the Classification of Gagging Problem index (CGP) and compared with 15 normal patients. Heart rate (HR), low-frequency/high-frequency ratio (L/H), the coefficient of component variation for high frequency (CCVHF), and the coefficient of variation of R-R intervals (CVRR) were assessed by heart rate variability on electrocardiogram. The measurement was recorded continuously for 1 min before and after dental mirror insertion. RESULTS: The insertion did not affect HR, L/H, CCVH, and CVRR in Group G2. HR did not change despite both increases in L/H and CCVHF after the insertion in Group G3. CONCLUSIONS: Patients with a gagging problem in G3, dental mirror insertion increased both parasympathetic and sympathetic nervous activities, despite no change in HR. PMID- 26681626 TI - Biodiversity: is there light for native fish assemblages at the end of the Anthropocene tunnel? PMID- 26681627 TI - Emotional Intelligence and resilience in mental health professionals caring for patients with serious mental illness. AB - Emotional Intelligence (EI) and resilience may be considered as prerequisites for mental health professionals caring for patients with serious mental illness (SMI), since they are often exposed to severe emotional stress during daily work. Accordingly, this cross-sectional study assessed both EI and resilience and their interrelationship in 61 individuals belonging to an assertive outreach team for patients suffering from SMI compared 61 control subjects without healthcare related working conditions. EI was assessed by means of the German version of the Mayer-Salovey-Caruso-Emotional-Intelligence Test (MSCEIT), resilience was assessed using the German version of the Resilience Scale. Both groups showed an average level of EI in all categories of the MSCEIT and indicated high levels of resilience. They did not differ significantly from each other, neither in terms of EI nor resilience. Correlation analysis revealed a positive association between EI and resilience, albeit small in magnitude. Our results suggest that mental health professionals are not more resilient and therefore not more 'protected' from stressors than the general population. Though this finding warrants cautious interpretation, the positive correlation between EI and resilience suggests that EI may be a potential target for education and training in order to strengthen resilience even in healthy individuals and vice versa. PMID- 26681628 TI - A consortium of rhizobacterial strains and biochemical growth elicitors improve cold and drought stress tolerance in rice (Oryza sativa L.). AB - In the present study, a consortium of two rhizobacteria Bacillus amyloliquefaciens Bk7 and Brevibacillus laterosporus B4, termed 'BB', biochemical elicitors salicylic acid and beta-aminobutyric acid (SB) and their mixture (BBSB) were investigated for cold and drought stress tolerance in rice plants. After withholding water for 16 days, rice plants treated with BBSB showed 100% survival, improved seedling height (35.4 cm), shoot number (6.12), and showed minimum symptoms of chlorosis (19%), wilting (4%), necrosis (6%) and rolling of leaves. Similarly, BB inoculation enhanced plant growth and reduced overall symptoms in rice seedlings subjected to 0 +/- 5 degrees C for 24 h. Our results imply several mechanisms underlying BB- and BBSB-elicited stress tolerance. In contrast to the control, both treatments significantly decreased leaf monodehydroascorbate (MDA) content and electrolyte leakage, and increased leaf proline and cholorophyll content. Moreover, activities of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) increased 3.0- and 3.6-fold, respectively. Moreover, expression of OsMYB3R-2, OsDIL, OsDREB1A and OsCDPK13 genes was significantly up-regulated, suggesting that these genes play important roles in abiotic stress tolerance of rice. In addition, bacterial strains Bk7 and B4 were able to produce high amounts of IAA and siderophores, and colonise the plant roots, while only strain Bk7 exhibited the capability to form biofilms and solubilise inorganic phosphate. This study indicates that the BB and BBSB bio formulations can be used to confer induced systematic tolerance and improve the health of rice plants subject to chilling and drought stress. PMID- 26681629 TI - The effect of nitrate supplementation on muscle contraction in healthy adults. AB - This study examined the effect of dietary supplementation with inorganic nitrate ([Formula: see text] ) on markers of contractile function in human knee extensors. In a double-blinded, randomized cross-over design, 18 (12 M) healthy participants undertook four days of supplementation with either nitrate-rich beetroot juice (NITRATE; days 1-3: 525 mg [Formula: see text], day 4: 1050 mg [Formula: see text]) or nitrate-depleted beetroot juice (PLACEBO). On the fourth day, isometric knee extension force was assessed during a series of voluntary and electrically evoked (stimulation) tests. In addition, muscular fatigue was examined in two separate continuous-stimulation (0.8 s tetanus with a 1:1 work:rest ratio for 102.4 s) fatigue tests, one with and one without blood flow restriction. There were no differences for maximum voluntary contraction, peak twitch force, half-relaxation time and the force-frequency relationship for stimulations up to 100 Hz between the NITRATE and PLACEBO trials. No differences between trials were observed in the non-restricted fatigue test, however NITRATE was found to attenuate the decline in force during the restricted test, such that the force at the 80 s mark (PLACEBO: 66 +/- 11 vs. NITRATE 74 +/- 9% of initial force; P = .01) and 102 s mark (PLACEBO: 47 +/- 8% vs. NITRATE 55 +/- 8%; P < .01) were significantly higher. These results suggest that four days of [Formula: see text] supplementation elicits peripheral responses in muscle that attenuate muscular fatigue during exhaustive exercise under hypovolemic conditions. This ergogenic action is likely attributable to improved Ca(2+) handling in the muscle, or enhanced perfusion during ischemia. PMID- 26681630 TI - Aerobic training alone or combined with strength training affects fitness in elderly: Randomized trial. AB - PURPOSE: To investigate if combined strength and aerobic training can enhance aerobic capacity in the elderly to a similar extent as aerobic training alone when training duration is matched. METHODS: Elderly men and women (age 63.2 +/- 4.7) were randomized into two intervention groups: an aerobic group (AG, n = 17) and a combined group (CG, n = 16). Subjects trained 40 minutes three times a week for 12 weeks. Both groups trained 20 minutes at 65% of heart rate reserve on ergometer cycles followed by another 20 minutes on the ergometer cycles for AG and 20-minute strength training for the lower body for CG. The primary outcome was VO2max. Secondary outcomes were maximal voluntary contraction (MVC) in isometric knee extension, 1 repetition maximum in three leg exercises, body fat, waist-to-hip ratio, blood pressure and score on the Health Survey Short Form 36 (SF-36). RESULTS: Both groups improved VO2max (p < .01) and MVC (p < .001). VO2max increased 17% confidence interval (CI) [7.4-26] in CG and 26% CI [14.1 38.2] in AG, with no significant difference between groups. MVC increased 22% CI [16.3-27.7] in CG and 9% CI [4.6-13.5] in AG with CG improving MVC more than AG (p < .01). CG's score on the general health dimension on the SF-36 health survey improved more than AG's score. CONCLUSION: Elderly can substitute a part of their aerobic training with strength training and still improve VO2max to a clinically significant degree when strength training is performed with large muscle groups subsequently to the aerobic training. Combined training additionally improves strength and self-assessed general health more than aerobic training alone. PMID- 26681631 TI - Validity of enriched enrollment, randomized withdrawal trials. PMID- 26681632 TI - Pitfalls in trials of "multimodal analgesia". PMID- 26681633 TI - Response: design challenges in trials of multimodal analgesia. PMID- 26681634 TI - Identification and isolation of Lactobacillus fructivorans from wilted alfalfa silage with and without molasses. AB - AIM: To gain insights into the bacterial species associated with anaerobic storage and aerobic stability of alfalfa silage. METHODS AND RESULTS: Wilted alfalfa silage (498 g dry matter kg(-1) ) was prepared with and without the addition of molasses. Aerobic spoilage tests were conducted at 5, 10 and 60 days after ensiling. The composition of fermentation products and the bacterial communities of silage were determined at 1, 3, 5 and 7 days after silo opening. Silage without molasses had small amounts of lactic and acetic acids detectable at silo opening but resisted deterioration due to aerobic spoilage for at least 5 days after opening. Resistance to aerobic deterioration in silage increased with the addition of molasses. The predominant bacterial species in molasses-added silage was Lactobacillus fructivorans, which was detected by denaturing gradient gel electrophoresis analysis. Different bacterial growth media were used for Lact. fructivorans isolation from alfalfa silage with added molasses: isolation was successful using liver infusion sake medium, but was unsuccessful when de Man, Rogosa and Sharpe medium was used. CONCLUSION: A nonconventional lactic acid bacterium (LAB) species may be involved in the high aerobic stability of alfalfa silage. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings demonstrate that culture-independent microbiota analysis may be useful in the isolation and identification of nonconventional LAB species involved in fermentation and the aerobic stability of silage. PMID- 26681635 TI - Nurses' attitudes towards pressure ulcer prevention in Turkey. AB - BACKGROUND: Pressure ulcers remain a major problem in healthcare system. Pressure ulcer incidence is widely accepted as an indicator for the quality of care. Positive attitudes towards pressure ulcer prevention have positive impacts on preventive care. AIMS AND OBJECTIVES: The aim of this study was to identify nurses' attitude towards pressure ulcer prevention. DESIGN: The study design was descriptive. SETTING AND SAMPLE: The study was carried out in a university hospital in Izmir, Turkey. The study population consisted of 660 nurses who work in medical and surgical clinics and intensive care units. The study sample consisted of 426 nurses who agreed to participate. METHOD: Attitude towards Pressure Ulcer Prevention Instrument was used in order to evaluate nurses' attitudes. Written permissions for ethical considerations and Attitude towards Pressure Ulcer Prevention Instrument permission were obtained. Data were collected between June and July 2014. The statistics program SPSS 18 packaged software was used in the analyses of data. RESULTS: The average age of the nurses who took part in the study was 31.86 +/- 7.09 years and the average work experience was 8.88 +/- 7.41 years; 36.9% (n: 157) were working in intensive care units. The nurses' average score on the Attitude towards Pressure Ulcer Prevention Instrument was 43.74 +/- 4.29 (84.12%). CONCLUSION: It was seen that the attitudes of the nurses towards the prevention of pressure ulcers was positive. To read guidelines and training time about pressure ulcer prevention affect positively attitudes towards the prevention of pressure ulcers. PMID- 26681636 TI - Redox Remodeling Is Pivotal in Murine Diaphragm Muscle Adaptation to Chronic Sustained Hypoxia. AB - Mechanisms underpinning chronic sustained hypoxia (CH)-induced structural and functional adaptations in respiratory muscles are unclear despite the clinical relevance to respiratory diseases. The objectives of the present study were to thoroughly assess the putative role of CH-induced redox remodeling in murine diaphragm muscle over time and the subsequent effects on metabolic enzyme activities, catabolic signaling and catabolic processes, and diaphragm muscle contractile function. C57Bl6/J mice were exposed to normoxia or normobaric CH (fraction of inspired oxygen = 0.1) for 1, 3, or 6 weeks. A second cohort was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine). After CH exposure, we performed two-dimensional redox proteomics with mass spectrometry, enzyme activity assays, and cell-signaling assays on diaphragm homogenates. We also assessed diaphragm isotonic contractile and endurance properties ex vivo. Global protein redox changes in the diaphragm after CH are indicative of oxidation. Remodeling of proteins key to contractile, metabolic, and homeostatic functions was observed. Several oxidative and glycolytic enzyme activities were decreased by CH. Redox-sensitive chymotrypsin like proteasome activity of the diaphragm was increased. CH decreased phospho forkhead box O3a (FOXO3a) and phospho-mammalian target of rapamycin content. Hypoxia-inducible factor-1alpha and phospho-p38 mitogen-activated protein kinase content was increased in CH diaphragm, and this was attenuated by antioxidant treatment. CH exposure decreased force- and power-generating capacity of the diaphragm, and this was prevented by antioxidant supplementation with N-acetyl cysteine but not tempol. Redox remodeling is pivotal for diaphragm adaptation to CH, affecting metabolic activity, atrophy signaling, and functional performance. Antioxidant supplementation may be useful as an adjunctive therapy in respiratory related diseases characterized by hypoxic stress. PMID- 26681637 TI - Two molecular assays for the rapid and inexpensive detection of GJB2 and GJB6 mutations. AB - The hypoacusia can be classified in two clinical forms: Syndromic (SHL) and Nonsyndromic (NSHL). In particular, the NSHL describes the 70-80% of hypoacusia cases and it is mainly due to genetic factors, which are causative of the deafness at the birth. The genetic hypoacusia presents different inheritance patterns: autosomal dominant (20%), autosomal recessive (80%), X-linked (1%), and mitochondrial (1%), respectively. To date, about 35 deafness-causative genes have been identified and most of them codify for connexin transmembrane proteins. Approximately 1:2500 children with NSHL carries mutations in the GJB2 and GJB6 (13q12) genes, which code for connexin 26 (Cx26) and connexin 30 (Cx30), respectively. In the Caucasian population, the most common mutations are 35delG, M34T and 167delT, and D13S1830. Given the frequency distribution of the four mutations in the Caucasian population and the pathogenic connection with NSHL, the development of accurate, rapid, and "low-cost" molecular assays should be strongly encouraged. To this purpose, we set up two different molecular assays (namely the Cx26 and Cx26-30 molecular assays) for the fast and inexpensive detection of 35delG, M34T, 167delT, and D13S1830 mutations. Both the molecular approaches showed to be accurate, sensitive, reproducible, and "low-cost" alternatives for the proper evaluation of the GJB2 and GJB6 genes, which are causative of NSHL. In conclusion, the Cx26 and Cx26-30 molecular assays can be applied to individual, preconception, prenatal, or postnatal screening for the causative-mutations of NSHL. PMID- 26681638 TI - Cold, dry air is associated with influenza and pneumonia mortality in Auckland, New Zealand. AB - The relationship between weather and influenza and pneumonia mortality was examined retrospectively using daily data from 1980 to 2009 in Auckland, New Zealand, a humid, subtropical location. Mortality events, defined when mortality exceeded 0.95 standard deviation above the mean, followed periods of anomalously cold air (ta.m. = -4.1, P < 0.01; tp.m. = -4.2, P < 0.01) and/or anomalously dry air (ta.m. = -4.1, P < 0.01; tp.m. = -3.8, P < 0.01) by up to 19 days. These results suggest that respiratory infection is enhanced during unusually cold conditions and during conditions with unusually low humidity, even in a subtropical location where humidity is typically high. PMID- 26681639 TI - Development of a real-time quantitative polymerase chain reaction assay for the detection of congenital human cytomegalovirus infection in urine samples. AB - A TaqMan real-time quantitative PCR (qPCR), based on amplification of HCMV UL54 gene specific sequence, was developed and compared with shell vial viral culture assay, the gold standard technique for the diagnosis of congenital HCMV infection, using urine samples collected from 110 newborns. The results indicate that this qPCR is slightly more sensitive than shell vial assay suggesting that qPCR may be considered a useful alternative for diagnosing congenital HCMV infection. PMID- 26681640 TI - [Qualitative and collaborative research with cancer patients. Experience narratives of treatments for peritoneal carcinomatosis]. AB - This CORCAN study is concerned with the way patients hospitalised for peritoneal carcinosis perceive surgical treatment and hyperthermic intraperitoneal chemotherapy (HIPEC). OBJECTIVES: (1) To identify and analyse, using concepts of social representation and accounts of the illness, characteristics of the way this treatment is experienced; (2) to inform doctors and healthcare workers about patients' representations, with a view to adjusting the treatment, the care and the information given to patients. METHODOLOGY: Fifty-eight directive and nondirective interviews were conducted longitudinally with 21 patients (13 women and 7 men) hospitalised for treatment by cell killing and HIPEC. RESULTS: Five important elements of concern were raised and discussed by the patients at different stages of the disease, then reported and discussed with the doctors and healthcare workers. These were patients' experiences of: the hyperthermic intraperitoneal chemotherapy (HIPEC), randomisation, intensive care, the effects of surgery on the digestive system, reorganising their diet, and returning home. PMID- 26681641 TI - [Fertility sparing treatment in women affected by cervical cancer larger than 2cm]. AB - OBJECTIVE: We report our experience on fertility sparing treatment in young women affected by cervical cancer of more than 2cm. METHODS: Between July 2012 and February 2014, five patients presenting cervical tumors larger than 2cm (IB1>2cm) (23-35) and wishing to preserve fertility have been treated at our institution. Laparoscopic pelvic and para-aortic lymphadenectomy was performed for all patients. When lymph nodes were free of disease, patients had neoadjuvant chemotherapy followed by surgical conservative treatment. RESULTS: Four patients underwent a cisplatin based neoadjuvant chemotherapy before conservative surgery: radical trachelectomy or simple trachelectomy. One patient with nodal involvement underwent a 3cycle chemotherapy followed by concurrent radiochemotherapy. Hematologic toxicity grade 3 was observed in one patient leading to a change of chemotherapy. Two patients showed complete disappearance of tumor and two a partial response to neoadjuvant treatment. After a mean follow up of 20.5months (14-33), no relapse was observed. To date, no pregnancy was obtained. CONCLUSION: Lymph node staging followed by neoadjuvant chemotherapy and radical trachelectomy seems to be a promising treatment scheme for patients with cervical tumors IB1>2cm pN0 seeking parenthood. PMID- 26681642 TI - [Pancreatic cancer: R rates vary with the definition of R0 and the pathology protocol]. PMID- 26681643 TI - [Pathological outcomes after laparoscopic and open surgery for rectal cancer: The ALaCaRT multicenter trial]. PMID- 26681644 TI - Molecular identification of Bigeyes (Perciformes, Priacanthidae) from Indian waters. AB - Thirty-five individuals of six priacanthid fish species were sampled from different localities along the coast of India covering the Arabian Sea and Bay of Bengal. The partial sequence of 16S rRNA and cytochrome oxidase subunit I (COI) genes were analyzed for species identification and phylogenetic relationship among the Indian priacanthids (Priacanthus hamrur, P. prolixus, P. blochii, P. sagittarius, Cookeolus japonicus, and Pristigenys refulgens). The intraspecies genetic distance ranged from 0.000 to 0.002, while distances varied from 0.008 to 0.157 interspecies based on 16S sequences. Using COI data analysis, the intraspecies genetic distance ranged from 0.000 to 0.005, while interspecies distances varied from 0.009 to 0.108. Several sequences labeled Priacanthus hamrur in GenBank are shown to be P. prolixus. We also observed cryptic speciation in Heteropriacanthus cruentatus. Partial sequences of 16S rRNA and COI genes provided phylogenetic information to distinguish thirteen species of priacanthids, indicating the usefulness of molecular markers in species identification. PMID- 26681645 TI - Gold-functionalized stainless-steel wire and tube for fiber-in-tube solid-phase microextraction coupled to high-performance liquid chromatography for the determination of polycyclic aromatic hydrocarbons. AB - A fiber-in-tube solid-phase microextraction device based on a gold-functionalized stainless-steel wire and tube was developed and characterized by scanning electron microscopy and energy dispersive X-ray spectroscopy. In combination with high-performance liquid chromatography, it was evaluated using six polycyclic aromatic hydrocarbons as model analytes. Important parameters including sampling rate, sample volume, organic solvent content and desorption time were investigated. Under optimized conditions, an online analysis method was established. The linearity was in the range of 0.15-50 MUg/L with correlation coefficients ranging from 0.9989 to 0.9999, and limits of detection ranged from 0.05 to 0.1 MUg/L. The method was applied to determine model analytes in mosquito repellent incense ash and river water samples, with recoveries in the range of 85 120%. PMID- 26681646 TI - Nickel-Titanium Shape-Memory Sawtooth-Arm Embracing Clamp for Complex Femoral Revision Hip Arthroplasty. AB - PURPOSES: To examine the clinical outcomes of patients treated with a nickel titanium shape-memory sawtooth-arm embracing clamp (Ni-Ti SSEC) in complex femoral revision surgery. METHODS: We retrospectively evaluated the outcomes for 21 complex femoral revision hip arthroplasties that we treated using an Ni-Ti SSEC. The Ni-Ti SSEC was used for various procedures, including the fixation of extremely long cortical windows (11 patients), femoral shaft osteotomy (4 patients), an extended trochanteric osteotomy (3 patients), and protection of a penetrated femoral cortex by a primary stem (3 patients). All patients received follow-up care for an average of 48.2 months. RESULTS: The mean time of Ni-Ti SSEC insertion intraoperatively was 6 minutes. The mean Harris Hip Score improved from 21.2 points before revision surgery to 83.1 points at the most recent examination. No implant failures or malunions occurred. Dislocation and deep infection occurred in 1 case during the follow-up period. CONCLUSIONS: Our results show that the embracing clamp is a simple and valid method for fixing osteotomies in treating complex femoral revision surgery. PMID- 26681647 TI - Methodology of "Physical and Rehabilitation Medicine practice, Evidence Based Position Papers: the European position" produced by the UEMS-PRM Section. AB - Since 2009 the Professional Practice Committee of the Physical and Rehabilitation Medicine (PRM) Section of the European Union (EU) of Medical Specialists (UEMS) is producing Position Papers (PPs) on the role of PRM physicians for patients with different health conditions or related topics of PRM Interest. These PPs represent the Official Position of the EU in the specific field. Until now, sixteen papers have been produced, recently collected in an e-book. To proceed with the future PPs, the UEMS PRM Section defines with this paper the methodological approach to a PP, so to have a common and validated scientific structure. The final aim is to increase the quality, representativeness and visibility of this production for the benefit of all PRM specialists in (and out) of Europe. The Position Papers must be Evidence Based (EBPP). Therefore it comprises a systematic review as well as a Consensus procedure among the EU Countries delegates. All the sections of an EBPP are presented in details (title, authors, abstract, introduction, material and methods, results, discussion, conclusion). The systematic review must focus on Cochrane reviews, randomised controlled trials and guidelines of PRM professional practice interest. The Consensus on the recommendations must be reached through a Delphi procedure, usually in four major rounds (each round can have repeated voting). The EBPP must produce Final Recommendations for Physical and Rehabilitation Medicine Professional Practice in Europe. The following overall structure for recommendations is suggested: one overall general recommendation on PRM professional practice; PRM physicians' role in Medical Diagnosis - ICD; PRM diagnosis and assessment according to ICF; PRM process (Project definition, Team, PRM interventions, Outcome criteria, Length and continuity of treatment); future research on PRM professional practice. PMID- 26681648 TI - Respiratory sinus arrhythmia reactivity to a sad film predicts depression symptom improvement and symptomatic trajectory. AB - Respiratory sinus arrhythmia (RSA) reactivity, an index of cardiac vagal tone, has been linked to self-regulation and the severity and course of depression (Rottenberg, 2007). Although initial data supports the proposition that RSA withdrawal during a sad film is a specific predictor of depression course (Fraguas, 2007; Rottenberg, 2005), the robustness and specificity of this finding are unclear. To provide a stronger test, RSA reactivity to three emotion films (happy, sad, fear) and to a more robust stressor, a speech task, were examined in currently depressed individuals (n=37), who were assessed for their degree of symptomatic improvement over 30weeks. Robust RSA reactivity to the sad film uniquely predicted overall symptom improvement over 30weeks. RSA reactivity to both sad and stressful stimuli predicted the speed and maintenance of symptomatic improvement. The current analyses provide the most robust support to date that RSA withdrawal to sad stimuli (but not stressful) has specificity in predicting the overall symptomatic improvement. In contrast, RSA reactivity to negative stimuli (both sad and stressful) predicted the trajectory of depression course. Patients' engagement with sad stimuli may be an important sign to attend to in therapeutic settings. PMID- 26681649 TI - Letter to the Editor. PMID- 26681650 TI - Inference of gene interaction networks using conserved subsequential patterns from multiple time course gene expression datasets. AB - MOTIVATION: Deciphering gene interaction networks (GINs) from time-course gene expression (TCGx) data is highly valuable to understand gene behaviors (e.g., activation, inhibition, time-lagged causality) at the system level. Existing methods usually use a global or local proximity measure to infer GINs from a single dataset. As the noise contained in a single data set is hardly self resolved, the results are sometimes not reliable. Also, these proximity measurements cannot handle the co-existence of the various in vivo positive, negative and time-lagged gene interactions. METHODS AND RESULTS: We propose to infer reliable GINs from multiple TCGx datasets using a novel conserved subsequential pattern of gene expression. A subsequential pattern is a maximal subset of genes sharing positive, negative or time-lagged correlations of one expression template on their own subsets of time points. Based on these patterns, a GIN can be built from each of the datasets. It is assumed that reliable gene interactions would be detected repeatedly. We thus use conserved gene pairs from the individual GINs of the multiple TCGx datasets to construct a reliable GIN for a species. We apply our method on six TCGx datasets related to yeast cell cycle, and validate the reliable GINs using protein interaction networks, biopathways and transcription factor-gene regulations. We also compare the reliable GINs with those GINs reconstructed by a global proximity measure Pearson correlation coefficient method from single datasets. It has been demonstrated that our reliable GINs achieve much better prediction performance especially with much higher precision. The functional enrichment analysis also suggests that gene sets in a reliable GIN are more functionally significant. Our method is especially useful to decipher GINs from multiple TCGx datasets related to less studied organisms where little knowledge is available except gene expression data. PMID- 26681651 TI - Housing priorities of persons with a spinal cord injury and their household members. AB - PURPOSE: This study aimed to identify the housing priorities of families living with persons with a spinal cord injury (SCI). METHOD: A new tool, the psycho environmental housing priorities (PEHP), was developed following the principles of Q-methodology and based on the psycho-environmental model. The PEHP includes 48 items concerning housing needs that were presented to 29 persons with SCI and to 30 of their household members to determine the more important needs in their home. RESULTS: Four different profiles of housing priorities emerged from the analysis, with persons with SCI and household members being dispersed across these profiles. Some needs, such as social contact and security, were identified as priorities in all the profiles while others, such as pleasure, were unique to some profiles. CONCLUSIONS: Our study highlights the heterogeneity of housing needs and the importance of addressing each family as unique when considering housing. The results also show that some housing needs ought to be considered because they were identified as important by everyone. Rehabilitation professionals could use the PEHP as a tool to help households living with a person with SCI plan their housing modifications to better meet the needs of all inhabitants. Implications for Rehabilitation Spinal cord injury causes impairment that significantly alters the relationship with the housing environment and modifies the relative importance of housing needs. Persons with SCI and household members have varying housing needs, as suggested by the identification of four distinct profiles of housing priorities using the psycho-environmental housing priorities (PEHP). The security and social contact needs emerge as important in all profiles and may be considered "universal needs". Rehabilitation professionals may use the PEHP as a tool to help households living with a person with SCI plan their housing modifications, for instance to identify compatible and conflicting priorities, and develop solutions agreeable to everyone. Using PEHP in the modification process could contribute to the household's feeling of autonomy and control. PMID- 26681652 TI - Promoter methylation of APC and RAR-beta genes as prognostic markers in non-small cell lung cancer (NSCLC). AB - Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-beta promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-beta promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-beta promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non tumor samples, and with smoking (P=0.004) in tumor samples. RAR-beta promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-beta methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. PMID- 26681653 TI - Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling. AB - Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75(NTR):TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs. PMID- 26681654 TI - Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer. AB - Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial. The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue. MATERIAL AND METHODS: A retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on ??Cp values using mixed modeling and presented as coefficients of variation (CV). RESULTS: Intra-tumor variance was approximately half of the variance observed between patients with a mean intra tumor CV of 56.4% (range 33.1-77.1%) and a mean inter-patient CV of 101.7% (range 48.8-152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal invasive difference equal to 0.60 Cp (95% CI: 0.30-0.89, p=0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10-1.46, p=0.027) for miR-375. Conclusion While the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics. PMID- 26681655 TI - Improving knowledge, technical skills, and confidence among pediatric health care providers in the management of chronic tracheostomy using a simulation model. AB - OBJECTIVE: The results from a recent national survey about catastrophic complications following tracheostomy revealed that the majority of events involved a loss of airway. Most of the events due to airway loss involved potentially correctable deficits in caregiver education. Training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the knowledge and confidence level of pediatric health care providers at a large tertiary care children's hospital in routine and emergency tracheostomy care and evaluated the efficacy of a comprehensive simulation-based tracheostomy educational program. METHODS: The prospective observational study was comprised of 33 subjects including pediatric residents, internal medicine-pediatric residents, pediatric hospitalist faculty physicians, and advanced practice registered nurses who are involved in the care of patients with tracheostomies within a tertiary-care children's hospital. The subjects completed self assessment questionnaires and objective multiple-choice tests before and after attending a comprehensive educational course that employed patient simulation. The outcome measurements included pre- and post-course questionnaires, pre- and post-course test scores, and observational data from the simulation sessions. RESULTS: Before the education and simulation, the subjects' comfort and confidence levels on a five-point Likert scale in performing routine tracheostomy tube care, routine tracheostomy tube change, and an emergency tracheostomy tube change were as follows (median (Q1, Q3)): 1 (1, 2), 1 (1, 2), and 1 (1, 2), respectively (n = 28). The levels of comfort and confidence after completing the course improved significantly to 4 (4, 5), 4 (4, 5), 4 (4, 5), respectively (P < 0.001) (n = 20). For the knowledge assessment, the pre-course test mean score was 0.53 +/- 0.50, and the scores on the post-course test improved significantly with a mean score of 0.82 +/- 0.39 (P < 0.001). During the educational intervention, specific deficiencies observed included a lack of understanding or familiarity with different types of tracheostomy tubes (e.g., cuffed versus uncuffed), physiological significance of the cuff, mechanism of action and physiological significance of the speaking valve, and the importance of the obturator in changing the tracheostomy tube. CONCLUSION: There is a need for improved tracheostomy education among pediatric health care providers. Incorporation of patient-simulation into a tracheostomy educational program was effective in improving knowledge, confidence, and skills. Pediatr Pulmonol. 2016;51:696-704. (c) 2015 Wiley Periodicals, Inc. PMID- 26681656 TI - Lean healthcare in developing countries: evidence from Brazilian hospitals. AB - The present study evaluates how five sectors of two Brazilian hospitals have implemented lean healthcare concepts in their operations. The main characteristics of the implementation process are analyzed in the present study: the motivational factor for implementation, implementation time, form (consultancy or internal), team (hospital and consultants), lean implementation continuity/sustainability, lean healthcare tools and methods implemented, problems/improvement opportunities, lean healthcare barriers faced during the implementation process, and critical factors that affected the implementation and the results obtained in each case. The case studies indicate that reducing patient lead times and costs and making financial improvements were the primary factors that motivated lean healthcare implementation in the hospitals studied. Several tools and methods were used in the cases studied, especially value stream mapping and DMAIC. The barriers found in both hospitals are primarily associated with the human factor. Additionally, the results obtained after implementation were analyzed and improvements in financial aspects, productivity and capacity, and lead time reduction of the analyzed sectors were observed. Further, this study also exhibited four propositions elaborated from the results obtained from the cases that highlighted barriers and challenges to lean healthcare implementation in developing countries. Two of these barriers are hospital organizational structure (and, consequently, how the senior management works with medical staff), and outsourcing hospital activities. This study also concluded that the initialization and maintenance of lean healthcare implementation rely heavily on external support because lean healthcare subject knowledge is not yet available in the healthcare organization, which represents a challenge. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26681657 TI - A test of the additivity of acute toxicity of binary-metal mixtures of ni with Cd, Cu, and Zn to Daphnia magna, using the inflection point of the concentration response curves. AB - Mixtures of metals are often present in surface waters, leading to toxicity that is difficult to predict. To provide data for development of multimetal toxicity models, Daphnia magna neonates were exposed to individual metals (Cd, Cu, Ni, Zn) and to binary combinations of those metals in standard 48-h lethality tests conducted in US Environmental Protection Agency moderately hard reconstituted water with 3 mg dissolved organic carbon (DOC)/L added as Suwannee River fulvic acid. Toxicity tests were performed with mixtures of Ni and 1) Cd, which is considerably more toxic than Ni; 2) Cu, which is less toxic than Cd but more toxic than Ni; and 3) Zn, which has a toxicity threshold similar to Ni. For each combination of metals in the binary mixtures, the concentration of 1 metal was held constant while the second metal was varied through a series that ranged from nonlethal to lethal concentrations; then the roles of the metals were reversed. Inflection points of the concentration-response curves were compared to test for additivity of toxicity. Sublethal concentrations of Ni caused less-than-additive toxicity with Cd, slightly less-than-additive toxicity with Zn, and greater-than additive toxicity with Cu. One explanation of these results might be competition among the metals for binding to biological ligands and/or dissolved organic matter. Therefore, models might have to incorporate sometimes competing chemical interactions to accurately predict metal-mixture toxicity. Environ Toxicol Chem 2016;35:1843-1851. (c) 2015 SETAC. PMID- 26681658 TI - Rare Earth Fluorescent Nanomaterials for Enhanced Development of Latent Fingerprints. AB - The most commonly found fingerprints at crime scenes are latent and, thus, an efficient method for detecting latent fingerprints is very important. However, traditional developing techniques have drawbacks such as low developing sensitivity, high background interference, complicated operation, and high toxicity. To tackle this challenge, we have synthesized two kinds of rare earth fluorescent nanomaterials, including the fluoresce red-emitting YVO4:Eu nanocrystals and green-emitting LaPO4:Ce,Tb nanobelts, and then used them as fluorescent labels for the development of latent fingerprints with high sensitivity, high contrast, high selectivity, high efficiency, and low background interference, on various substrates including noninfiltrating materials, semi infiltrating materials, and infiltrating materials. PMID- 26681659 TI - Computer-aided diagnosis for estimating the malignancy grade of hepatocellular carcinoma using contrast-enhanced ultrasound: an ROC observer study. AB - BACKGROUND & AIMS: We are developing a computer-aided diagnosis (CAD) system for estimating the malignancy grade of hepatocellular carcinoma (HCC) using contrast enhanced ultrasound (CEUS). In this study, observers estimated the malignancy grade of HCC with and without the cues provided by CAD. MATERIALS AND METHODS: Institutional review board approval was obtained and informed consent was waived. A total of 232 histologically confirmed HCCs were studied: 76 well-differentiated HCC (w-HCC), 133 moderately differentiated HCC (m-HCC), and 23 poorly differentiated HCC (p-HCC). In this observer study, CEUS vascular images acquired using the maximum intensity projection technique were displayed together with static B-mode and Kupffer-phase (defined as 10 min after injection) images. Five hepatologists independently assigned confidence ratings for the malignancy grade of each HCC. Each hepatologist first read each case without CAD and then immediately afterwards with CAD. The observers' rating data were evaluated by multireader multicase receiver operating characteristic (ROC) analysis. RESULTS: The overall sensitivity of our CAD system for discrimination between three histological differentiation grades of HCC was 87.5% (203/232). For discrimination between w-HCC and m/p-HCC, the mean area under the ROC curve (AUC) for the five observers was significantly improved from 0.779 +/- 0.074 to 0.872 +/- 0.090 with CAD (P = 0.0069). For discrimination between m-HCC and p-HCC, the mean AUC was also significantly improved from 0.713 +/- 0.107 to 0.863 +/- 0.101 with CAD (P = 0.0321). CONCLUSION: The use of our CAD system can significantly improve the diagnostic performance of hepatologists in discriminating between three histological differentiation grades of HCC using CEUS. PMID- 26681660 TI - [Evaluation of the efficacy of medical screening of blood donors on preventing blood transfusion-transmitted infectious agents]. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of medical screening to retain blood donors in window period by comparing the seroprevalence of infectious agents (HIV, hepatitis B and C, syphilis) in deferred versus accepted blood donors. MATERIALS AND METHODS: This prospective and transversal study was performed during 4 months in the National Blood Transfusion Center in Dakar (Senegal). We conducted a convenience sampling comparing the seroprevalence of infectious agents (HIV, HBsAg, HCV and syphilis) in deferred versus accepted blood donors after medical selection. RESULTS: In total, 8219 blood donors were included. Medical selection had authorized 8048 donors (97.92%) and deferred donors were 171 (2.08%). The prevalence of HIV was higher in the deferred than in accepted blood donors (1.75% vs. 0.05%) (P=0.0003; OR=35.91), as well as for HBsAg (12.87% vs. 7.35%) (P=0.006; OR=1.86). HCV antibodies were present in 0.71% of accepted blood donors and 0.58% in deferred blood donors (P=0.65; OR=0.82). Only accepted donors had brought the infection of syphilis (0.34%) (P=0.56; OR=0). CONCLUSION: Medical selection is efficient to exclude blood donors at high risk of HIV transmission and to a lesser extent of HBV. However, current medical screening procedures do not allow us to exclude donors asymptomatic carriers of HCV and syphilis. PMID- 26681661 TI - Bone-impacted fibular free flap: Long-term dental implant success and complications compared to traditional fibular free tissue transfer. AB - BACKGROUND: The purpose of this study was to compare complications and dental implant success between the bone-impacted fibula free flap (BIFFF) and the traditional fibular free flap used in mandibular and midface reconstruction. METHODS: Retrospective review of all patients undergoing BIFFF or traditional fibular free flap reconstruction from 2001 to 2009 was undertaken. Complications related to the BIFFF and traditional fibular free flap site of reconstruction were compared. Dental implant success rates for each type of flap were compared at 1-year intervals for 5 years. RESULTS: One hundred fourteen patients underwent 81 BIFFFs and 35 traditional fibular free flaps. No significant difference in complications between BIFFF (20.9%) and traditional fibular free flap (25.7%) reconstruction was observed. Logistic regression analysis revealed only the site as a predictor of both single and multiple complications. At 5 years postimplantation, dental implant success rates were 95.5% and 77.1% for BIFFF and traditional fibular free flap, respectively (p = .006). CONCLUSION: BIFFF reconstruction is a novel surgical technique that may improve long-term dental implant success rates with no additional risk of complications. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1783-E1787, 2016. PMID- 26681662 TI - One in Four Questioned Children Faces Problems Regarding Reintegration Into Physical Education at School After Treatment for Pediatric Cancer. AB - Resumption of physical activity and reintegration into social surroundings after treatment for pediatric cancer is of high importance to recover from the burden of disease and treatment and to positively influence long-term health outcomes. Eighty-three children who had completed intensive treatment for pediatric cancer were surveyed regarding their participation in physical education at school (PES). The results show a concerning low rate of participation, particularly in children treated for pediatric bone tumors, and associated barriers. Reported reasons for quitting PES seem to be conquerable by individual and entity-related support to enable participation according to the children's desire. PMID- 26681663 TI - Total endovascular arch replacement: Are we there yet? Are we there yet?.... PMID- 26681664 TI - Rituximab for subcutaneous delivery: Clinical management principles from a nursing perspective. AB - Nurses play an integral role in administering treatments to patients with non Hodgkin's lymphomas. Intravenous (IV) rituximab was approved by the Australian Therapeutic Goods Administration in 1998, and a novel subcutaneous (SC) formulation was approved in 2014. Fixed-dose SC rituximab is highly concentrated; co-formulation with a fully human recombinant vorhyaluronidase alfa enzyme helps overcome the physiological barriers of the SC space, facilitating drug dispersion. Despite a different pharmacokinetic profile to the IV preparation, SC rituximab demonstrates a comparable efficacy/safety profile. Most frequently occurring rituximab-related adverse events include neutropenia, nausea and constipation, and administration-related reactions are more frequent with the SC preparation. Compared with IV, SC delivery reduces treatment times and nurse workload, and patients report greater comfort and convenience. This article sets out nursing considerations for optimal administration of SC rituximab, including premedication, drug handling/preparation, injection technique, after-care and management of adverse events, particularly administration-related reactions. PMID- 26681665 TI - Prevention and management of obinutuzumab-associated toxicities: Australian experience. AB - Patients with chronic lymphocytic leukaemia (CLL) are typically diagnosed at an advanced age and may have multiple co-existing conditions, augmenting the challenges of treating their CLL. Aggressive cytotoxic therapies are often poorly tolerated in this patient population. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody indicated in combination with chlorambucil for previously untreated CLL. The approval of this drug was based on the pivotal CLL11 trial, which demonstrated longer progression-free survival vs. rituximab/chlorambucil and chlorambucil alone in patients with significant co existing medical conditions and/or poor renal function. However, a higher risk of infusion-related reactions (IRRs) was demonstrated with obinutuzumab-based therapy. We highlight important nursing care considerations to help prevent and successfully manage IRRs and other important adverse events, to improve the treatment experience of patients receiving obinutuzumab infusions and to enable them to complete their treatment and receive optimal benefit. Premedication, drug handling, dosing, administration, monitoring and documentation are discussed. PMID- 26681666 TI - Multiple imputation for IPD meta-analysis: allowing for heterogeneity and studies with missing covariates. AB - Recently, multiple imputation has been proposed as a tool for individual patient data meta-analysis with sporadically missing observations, and it has been suggested that within-study imputation is usually preferable. However, such within study imputation cannot handle variables that are completely missing within studies. Further, if some of the contributing studies are relatively small, it may be appropriate to share information across studies when imputing. In this paper, we develop and evaluate a joint modelling approach to multiple imputation of individual patient data in meta-analysis, with an across-study probability distribution for the study specific covariance matrices. This retains the flexibility to allow for between-study heterogeneity when imputing while allowing (i) sharing information on the covariance matrix across studies when this is appropriate, and (ii) imputing variables that are wholly missing from studies. Simulation results show both equivalent performance to the within-study imputation approach where this is valid, and good results in more general, practically relevant, scenarios with studies of very different sizes, non negligible between-study heterogeneity and wholly missing variables. We illustrate our approach using data from an individual patient data meta-analysis of hypertension trials. (c) 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 26681667 TI - NICE told to back off "national policy issues". PMID- 26681668 TI - Changes in Under-5 Mortality Rate and Major Childhood Diseases: A Country-Level Analysis. AB - Under-5 child mortality decreased throughout the world by 49% from 1990 to 2013. However, it is unknown if this reduction was more effectively achieved in countries with a higher child mortality burden. We investigated the reduction of cause-specific global child mortality burden in 2000-2010. A total of 195 countries were selected for this analysis. A random-effect or fixed-effect model was chosen based on the Hausman test. Countries with a higher child mortality rate performed better with regard to the prevention of child deaths from major infectious diseases, but cause-specific progress was highly variable by disease within each country. Pneumonia-specific progress was much slower than that for diarrhea, and neonatal-specific child mortality increased in some countries. With a few exceptions, the overall performance in the countries with the largest share of child deaths was not good. This study identified priority interventions for child survival in the post-2015 period. PMID- 26681669 TI - Changes in Quality of Life After a Suicide Attempt. AB - The aim of this follow-up study was to examine factors related to a suicide attempt within 3 months of a prior attempt. Participants were recruited from a suicide-prevention center. Of 96 suicidal individuals who had participated in the baseline study, only 51 completed all measures at follow-up assessment. Study results showed that suicidal individuals who reattempted suicide during the first 3 months of follow-up care exhibited lower mean scores on all four domains of the brief version of the World Health Organization Quality-of-Life Instrument at follow-up assessment than at baseline. In contrast, individuals who did not reattempt suicide had higher quality-of-life scores across all domains between baseline and 3 months. The reattempt and no-reattempt groups differed significantly in the physical health and environmental domains. These results can be used by nurses to develop their abilities to recognize and prevent suicide reattempts in high-risk groups. PMID- 26681670 TI - Living Arrangements and Quality of Life: Mediation by Physical Function and Depression. AB - Living arrangements are often assumed to be associated with health-related quality of life (HRQoL) among older adults. This study aimed to explore how living arrangements affect HRQoL. A cross-sectional survey was conducted to examine the relationships between HRQoL, activities of daily living (ADLs), depression, and living arrangements among older adults. A total of 220 community dwelling older adults and 231 nursing home residents completed the questionnaires. The path analysis indicated that the older adults' living arrangement did not directly influence their HRQoL, but it had indirect effects through ADLs and depression. The whole model explained 55% of the variance of HRQoL, which suggests that living in nursing homes does not directly cause older adults' poor HRQoL, but poor ADLs and more severe depression among nursing home residents lead to poor HRQoL. To improve their HRQoL, additional focus should be placed on maintaining ADLs and increasing community participation. PMID- 26681671 TI - Highly Efficient Storage of Pulse Energy Produced by Triboelectric Nanogenerator in Li3V2(PO4)3/C Cathode Li-Ion Batteries. AB - Triboelectric nanogenerator (TENG) has been considered as a new type of energy harvesting technology, which employs the coupling effects of triboelectrification and electrostatic induction. One key factor having limited its application is the energy storage. In this work, a high performance Li3V2(PO4)3/C material synthesized by low-cost hydrothermal method followed with subsequent annealing treatment was studied to efficiently store the power generated by a radial arrayed rotary TENG. Not only does the Li3V2(PO4)3/C exhibit a discharge capacity of 128 mAh g(-1) at 1 C with excellent cyclic stability (capacity retention is 90% after 1000 cycles at a rate of 5 C) in Li-ion battery, but also shows outstanding energy conversion efficiency (83.4%) compared with the most popular cathodic materials: LiFePO4 (74.4%), LiCoO2 (66.1%), and LiMn2O4 (73.6%) when it was charged by high frequency and large current electricity directly from by TENG. PMID- 26681673 TI - Regulation of PD-L1: a novel role of pro-survival signalling in cancer. AB - Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1alpha and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR 197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation. PMID- 26681674 TI - Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes. AB - BACKGROUND: The ability to perform comprehensive profiling of cancers at high resolution is essential for precision medicine. Liquid biopsies using shed exosomes provide high-quality nucleic acids to obtain molecular characterization, which may be especially useful for visceral cancers that are not amenable to routine biopsies. PATIENTS AND METHODS: We isolated shed exosomes in biofluids from three patients with pancreaticobiliary cancers (two pancreatic, one ampullary). We performed comprehensive profiling of exoDNA and exoRNA by whole genome, exome and transcriptome sequencing using the Illumina HiSeq 2500 sequencer. We assessed the feasibility of calling copy number events, detecting mutational signatures and identifying potentially actionable mutations in exoDNA sequencing data, as well as expressed point mutations and gene fusions in exoRNA sequencing data. RESULTS: Whole-exome sequencing resulted in 95%-99% of the target regions covered at a mean depth of 133-490*. Genome-wide copy number profiles, and high estimates of tumor fractions (ranging from 56% to 82%), suggest robust representation of the tumor DNA within the shed exosomal compartment. Multiple actionable mutations, including alterations in NOTCH1 and BRCA2, were found in patient exoDNA samples. Further, RNA sequencing of shed exosomes identified the presence of expressed fusion genes, representing an avenue for elucidation of tumor neoantigens. CONCLUSIONS: We have demonstrated high-resolution profiling of the genomic and transcriptomic landscapes of visceral cancers. A wide range of cancer-derived biomarkers could be detected within the nucleic acid cargo of shed exosomes, including copy number profiles, point mutations, insertions, deletions, gene fusions and mutational signatures. Liquid biopsies using shed exosomes has the potential to be used as a clinical tool for cancer diagnosis, therapeutic stratification and treatment monitoring, precluding the need for direct tumor sampling. PMID- 26681675 TI - Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples. AB - BACKGROUND: Next-generation sequencing (NGS) of tumour samples is a critical component of personalised cancer treatment, but it requires high-quality DNA samples. Routine neutral-buffered formalin (NBF) fixation has detrimental effects on nucleic acids, causing low yields, as well as fragmentation and DNA base changes, leading to significant artefacts. PATIENTS AND METHODS: We have carried out a detailed comparison of DNA quality from matched samples isolated from high grade serous ovarian cancers from 16 patients fixed in methanol and NBF. These experiments use tumour fragments and mock biopsies to simulate routine practice, ensuring that results are applicable to standard clinical biopsies. RESULTS: Using matched snap-frozen tissue as gold standard comparator, we show that methanol-based fixation has significant benefits over NBF, with greater DNA yield, longer fragment size and more accurate copy-number calling using shallow whole-genome sequencing (WGS). These data also provide a new approach to understand and quantify artefactual effects of fixation using non-negative matrix factorisation to analyse mutational spectra from targeted and WGS data. CONCLUSION: We strongly recommend the adoption of methanol fixation for sample collection strategies in new clinical trials. This approach is immediately available, is logistically simple and can offer cheaper and more reliable mutation calling than traditional NBF fixation. PMID- 26681676 TI - Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4). AB - BACKGROUND: RECORD-1 demonstrated clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) previously treated with sunitinib, sorafenib, or both; prior treatment with cytokines, bevacizumab, and chemotherapy was also permitted. RECORD-4 prospectively assessed everolimus in a purely second line setting. METHODS: Patients with clear-cell mRCC were enrolled into one of three cohorts based on first-line therapy with sunitinib, other anti-VEGF agents, or cytokines. Patients were treated with everolimus 10 mg/day until progression (RECIST, v1.0) or intolerance. The primary end point was progression-free survival (PFS) per investigator review. Data cutoff was 1 September 2014, for the primary analysis and 26 June 2015, for the final overall survival (OS) analysis. RESULTS: Enrolled patients (N = 134) previously received sunitinib (n = 58), other anti-VEGF therapy (n = 62; sorafenib, 23; bevacizumab, 16; pazopanib, 13; tivozanib, 5; and axitinib, 3), or cytokines (n = 14). Overall median age was 59 years, and most patients were men (68%) and of favorable/intermediate MSKCC risk (52/37%). Overall median PFS was 7.8 months [95% confidence interval (CI) 5.7 11.0]; in the cohorts, it was 5.7 months (95% CI 3.7-11.3) with previous sunitinib, 7.8 months (95% CI 5.7-11.0) with other previous anti-VEGF therapy, and 12.9 months [95% CI 2.6-not estimable (NE)] with previous cytokines. Overall, 67% of patients achieved stable disease as their best objective response. At final OS analysis, total median OS was 23.8 months (95% CI 17.0-NE) and, in the cohorts, it was 23.8 months (95% CI 13.7-NE) with previous sunitinib, 17.2 months (95% CI 11.9-NE) with other previous anti-VEGF therapy, and NE (95% CI 15.9-NE) with previous cytokine-based therapy. Overall, 56% of patients experienced grade 3 or 4 adverse events (regardless of relationship to study drug). CONCLUSIONS: These results confirm the PFS benefit of second-line everolimus after first-line sunitinib or other anti-VEGF therapies. The safety profile of everolimus was consistent with previous experience. CLINICAL TRIAL NAME AND IDENTIFIER: Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (RECORD-4), ClinicalTrials.gov identifier, NCT01491672. PMID- 26681677 TI - Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study. AB - BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. PATIENTS AND METHODS: Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: <=10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen Johansen method. RESULTS: Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent <=10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt <=3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel >=2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent <=10 or >25 ng/ml. CONCLUSION: We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. CLINICAL TRIAL NUMBER: NCT00672282. PMID- 26681678 TI - Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial. AB - BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (>=2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum. EUDRACT NUMBER: 2011-001298-17. PMID- 26681679 TI - Is it possible to encourage hope in non-advanced cancer patients? We must try. AB - BACKGROUND: Data are lacking on the relationship between hope and other variables in non-advanced cancer patients. The study explored the relationship between hope, symptoms, needs, and spirituality/religiosity in patients treated in a supportive care unit (SCU). PATIENTS AND METHODS: From September 2013 to March 2014, the consecutive patients who accepted to complete: (i) Needs Evaluation Questionnaire (NEQ), (ii) the Edmonton Symptom Assessment System (ESAS), (iii) Hope Herth Index (HHI), and (iv) the System of Belief Inventory (SBI) were enrolled. Moreover, clinical/demographic data were collected and the findings were analyzed. RESULTS: A total of 276 patients who completed the HHI questionnaire (participation rate 276/300 = 92%) were included; 131 reported HHI total score >37 (median value). The majority of patients had a Karnofsky performance status >80; 71% were on cancer therapies, and only 29 patients had metastases or relapse. Patients with higher HHI scores were less educated (P = 0.012), reported lower ESAS total score (15.4 versus 22.6, P < 0.001), and had less often been referred to a psychologist previously to the study (P = 0.002); patients with a higher HHI score also reported higher spirituality (P < 0.001). Some NEQ items resulted significantly associated with HHI score after adjustment for other variables: the need to have sincere clinicians (beta = -2.7), better dialogue (beta = -2.1), and more reassurance from the clinicians (beta = -2.5); better attention (beta = -4.4) and respect for intimacy (beta = -3.3) from nurses; to speak with people who have the same illness experience (beta = -2.5), to be more reassured by relatives (beta = -3.3) and to feel less abandoned (beta = -4.3). Higher SBI scores were independently associated with higher HHI scores (beta = 1.7 for 10 points increase). CONCLUSIONS: In cancer patients, hope can be encouraged by clinicians through dialogue, sincerity, and reassurance, as well as assessing and considering the patients' needs (above all the psycho-emotional), symptoms, psychological frailty, and their spiritual/religious resources. PMID- 26681680 TI - A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer. AB - BACKGROUND: We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). PATIENTS AND METHODS: Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). RESULTS: Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37 0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. CONCLUSION: The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. CLINICAL TRIALS NUMBER: Japan Pharmaceutical Information Center: JapicCTI-111554. PMID- 26681681 TI - Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel. AB - Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or >=2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients. PMID- 26681682 TI - Genetic testing in a cohort of young patients with HER2-amplified breast cancer. AB - BACKGROUND: Young age at diagnosis for breast cancer raises the question of genetic susceptibility. We explored breast cancer susceptibility genes testing on <=40-year-old patients with HER2-amplified invasive breast cancer. PATIENTS AND METHODS: Patients were selected from a large UK cohort study. The inclusion criterion was age <=40 at diagnosis with confirmed HER2-amplified breast cancer. The probability of finding a BRCA gene mutation was calculated based on family history. Genetic testing used was either clinical testing for BRCA1 and BRCA2, with a subset also tested for TP53 mutations, or research-based testing using a typical panel comprising 17 breast cancer susceptibility genes (CSGs) including BRCA1, BRCA2 and TP53. RESULTS: Of the 591 eligible patients, clinical testing results were available for 133 cases and an additional 263 cases had panel testing results. BRCA testing across 396 cases found 8 BRCA2 (2%) and 6 BRCA1 (2%) pathogenic mutations. Of the 304 patients tested for TP53 mutations, overall 9 (3%) had deleterious TP53 mutations. Of the 396 patients, 101 (26%) met clinical criteria for BRCA testing (>=10% probability), among whom 11% had pathogenic BRCA mutations (6 BRCA2, 5 BRCA1). Where the probability was calculated to be <10%, only 4 of 295 (1%) patients had BRCA mutations. Among the 59 patients who had TP53 testing meeting the 10% threshold, 7 had mutations (12%). Likely functionally deleterious mutations in 14 lower penetrance CSGs were present in 12 of 263 (5%) panel-tested patients. CONCLUSION: Patients aged <41 at diagnosis with HER2+ breast cancer and no family history of breast cancer can be reassured that they have a low chance of being a high-risk gene carrier. If there is a strong family history, not only BRCA but also TP53 gene testing should be considered. The clinical utility of testing lower penetrance CSGs remains unclear. PMID- 26681683 TI - The GILDA trial finds no survival benefit from intensified screening after primary resection of colorectal cancer: the PulMiCC trial tests the survival benefit of pulmonary metastasectomy for detected asymptomatic lung metastases. PMID- 26681684 TI - Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial. AB - BACKGROUND: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade >=2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. RESULTS: After a median follow-up of 74 months, 5 patients developed a grade >=2 RISF. No significant difference was observed between arms A and B. Neither grade >=2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade >=2 RISF was significantly lower compared with those who developed grade <=1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 * 10(-9)) and rs1182532 (P = 3.6 * 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33. CONCLUSIONS: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. REGISTERED CLINICAL TRIAL: NCT00208273. PMID- 26681685 TI - Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis. AB - BACKGROUND: Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy improves response rates and survival in patients with B-cell non Hodgkin lymphoma (NHL). However, rituximab induces a transient B-cell depletion and a dose-dependent T-cell inactivation that could impair T-cell immunosurveillance. The impact of rituximab on second primary malignancy (SPM) risk remains unclear so far. We thus carried out a systematic review to compare SPM risk among patients treated or not with rituximab. PATIENTS AND METHODS: We retrieved trials from MEDLINE and EMBASE and updated data presented at American Society of Hematology and American Society of Clinical Oncology meetings from 1998 to 2013. We selected randomized, controlled trials addressing newly or relapsed/progressive B-cell NHL in which randomization arms differed only from rituximab administration. Two authors extracted data and assessed the study quality. RESULTS: We analyzed nine trials involving 4621 patients. At a median follow-up of 73 months, a total of 169 SPMs were observed in patients randomized to rituximab compared with 165 SPMs in patients not randomized to rituximab (OR = 0.88; 95% CI 0.66-1.19). The proportion of females, histology subtypes, use of rituximab in first line or in maintenance did not influence SPM risk (P = 0.94, P = 0.80, P = 0.87, P = 0.87, respectively). Cumulative exposure through prolonged administration in trials with rituximab maintenance did not contribute to an increased risk of SPM (P = 0.86). CONCLUSION: Our meta-analysis suggests no SPM predisposition among NHL survivors exposed to rituximab at a median follow-up of 6 years. PMID- 26681686 TI - Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group. AB - Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals. PMID- 26681687 TI - Experiences of diagnosing autism spectrum disorder: A survey of professionals in the United Kingdom. AB - To date, research exploring experiences of diagnosing autism spectrum disorder has largely focused on parental perspectives. In order to obtain a more complete account of the autism spectrum disorder diagnostic process, it is essential that the views and experiences of professionals are heard. In this study, 116 multidisciplinary professionals involved in diagnosing autism spectrum disorder in the United Kingdom completed an online questionnaire exploring their experiences and opinions of three key areas of service: accessibility, the diagnostic process and post-diagnostic support. Although professionals were largely satisfied with service accessibility, around 40% of services were failing to provide timely assessments. Standardised diagnostic tools were perceived as helpful and were used consistently, but concerns were raised about their validity in detecting atypical autism spectrum disorder presentations (e.g. females). Several challenges regarding giving autism spectrum disorder diagnoses were reported; these included making sure caregivers understood the diagnosis, pitching information at the correct level and managing distress. Furthermore, the practice of 'upgrading' to a diagnosis of autism spectrum disorder in uncertain or complex cases was reported by many, albeit infrequently, and reasons for this varied widely. Professionals expressed dissatisfaction with post-diagnostic provision, especially onward and long-term support options. They also felt that service improvements were required across populations and across the three key areas of service. PMID- 26681688 TI - Locking-to-unlocking system is an efficient strategy to design DNA/silver nanoclusters (AgNCs) probe for human miRNAs. AB - MicroRNAs (miRNAs), small non-coding RNA molecules, are important biomarkers for research and medical purposes. Here, we describe the development of a fast and simple method using highly fluorescent oligonucleotide-silver nanocluster probes (DNA/AgNCs) to efficiently detect specific miRNAs. Due to the great sequence diversity of miRNAs in humans and other organisms, a uniform strategy for miRNA detection is attractive. The concept presented is an oligonucleotide-based locking-to-unlocking system that can be endowed with miRNA complementarity while maintaining the same secondary structure. The locking-to-unlocking system is based on fold-back anchored DNA templates that consist of a cytosine-rich loop for AgNCs stabilization, an miRNA recognition site and an overlap region for hairpin stabilization. When an miRNA is recognized, fluorescence in the visible region is specifically extinguished in a concentration-dependent manner. Here, the exact composition of the fold-back anchor for the locking-to-unlocking system has been systematically optimized, balancing propensity for loop-structure formation, encapsulation of emissive AgNCs and target sensitivity. It is demonstrated that the applied strategy successfully can detect a number of cancer related miRNAs in RNA extracts from human cancer cell lines. PMID- 26681690 TI - Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism. AB - As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress dependent manner. PMID- 26681689 TI - Transcriptional regulatory networks in Arabidopsis thaliana during single and combined stresses. AB - Differentially evolved responses to various stress conditions in plants are controlled by complex regulatory circuits of transcriptional activators, and repressors, such as transcription factors (TFs). To understand the general and condition-specific activities of the TFs and their regulatory relationships with the target genes (TGs), we have used a homogeneous stress gene expression dataset generated on ten natural ecotypes of the model plant Arabidopsis thaliana, during five single and six combined stress conditions. Knowledge-based profiles of binding sites for 25 stress-responsive TF families (187 TFs) were generated and tested for their enrichment in the regulatory regions of the associated TGs. Condition-dependent regulatory sub-networks have shed light on the differential utilization of the underlying network topology, by stress-specific regulators and multifunctional regulators. The multifunctional regulators maintain the core stress response processes while the transient regulators confer the specificity to certain conditions. Clustering patterns of transcription factor binding sites (TFBS) have reflected the combinatorial nature of transcriptional regulation, and suggested the putative role of the homotypic clusters of TFBS towards maintaining transcriptional robustness against cis-regulatory mutations to facilitate the preservation of stress response processes. The Gene Ontology enrichment analysis of the TGs reflected sequential regulation of stress response mechanisms in plants. PMID- 26681691 TI - Genome-wide analysis reveals NRP1 as a direct HIF1alpha-E2F7 target in the regulation of motorneuron guidance in vivo. AB - In this study, we explored the existence of a transcriptional network co regulated by E2F7 and HIF1alpha, as we show that expression of E2F7, like HIF1alpha, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1alpha. Our genome-wide analysis uncovers a transcriptional network that is directly controlled by HIF1alpha and E2F7, and demonstrates both stimulatory and repressive functions of the HIF1alpha -E2F7 complex. Among this network we reveal Neuropilin 1 (NRP1) as a HIF1alpha-E2F7 repressed gene. By performing in vitro and in vivo reporter assays we demonstrate that the HIF1alpha-E2F7 mediated NRP1 repression depends on a 41 base pairs 'E2F binding site hub', providing a molecular mechanism for a previously unanticipated role for HIF1alpha in transcriptional repression. To explore the biological significance of this regulation we performed in situ hybridizations and observed enhanced nrp1a expression in spinal motorneurons (MN) of zebrafish embryos, upon morpholino-inhibition of e2f7/8 or hif1alpha Consistent with the chemo-repellent role of nrp1a, morpholino-inhibition of e2f7/8 or hif1alpha caused MN truncations, which was rescued in TALEN-induced nrp1a(hu10012) mutants, and phenocopied in e2f7/8 mutant zebrafish. Therefore, we conclude that repression of NRP1 by the HIF1alpha-E2F7 complex regulates MN axon guidance in vivo. PMID- 26681692 TI - Biogenesis and growth phase-dependent alteration of 5 methoxycarbonylmethoxyuridine in tRNA anticodons. AB - Post-transcriptional modifications at the anticodon first (wobble) position of tRNA play critical roles in precise decoding of genetic codes. 5 carboxymethoxyuridine (cmo(5)U) and its methyl ester derivative 5 methoxycarbonylmethoxyuridine (mcmo(5)U) are modified nucleosides found at the anticodon wobble position in several tRNAs from Gram-negative bacteria. cmo(5)U and mcmo(5)U facilitate non-Watson-Crick base pairing with guanosine and pyrimidines at the third positions of codons, thereby expanding decoding capabilities. By mass spectrometric analyses of individual tRNAs and a shotgun approach of total RNA from Escherichia coli, we identified mcmo(5)U as a major modification in tRNA(Ala1), tRNA(Ser1), tRNA(Pro3) and tRNA(Thr4); by contrast, cmo(5)U was present primarily in tRNA(Leu3) and tRNA(Val1). In addition, we discovered 5-methoxycarbonylmethoxy-2'-O-methyluridine (mcmo(5)Um) as a novel but minor modification in tRNA(Ser1). Terminal methylation frequency of mcmo(5)U in tRNA(Pro3) was low (~30%) in the early log phase of cell growth, gradually increased as growth proceeded and reached nearly 100% in late log and stationary phases. We identified CmoM (previously known as SmtA), an AdoMet-dependent methyltransferase that methylates cmo(5)U to form mcmo(5)U. A luciferase reporter assay based on a +1 frameshift construct revealed that terminal methylation of mcmo(5)U contributes to the decoding ability of tRNA(Ala1). PMID- 26681693 TI - Binding of transcription factor GabR to DNA requires recognition of DNA shape at a location distinct from its cognate binding site. AB - Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding. In silico predictions suggest that the bridging DNA sequence is likely to be bendable in one direction and kinetic analysis of mutant DNA sequences with biolayer interferometry, allowed the independent quantification of the relative contribution of DNA base and shape recognition in the GabR-DNA interaction. These indicate that the two cognate binding sites as well as the bendability of the DNA sequence in between these sites are required to form a stable complex. The mechanism of GabR-DNA interaction provides an example where the correct shape of DNA, at a clearly distinct location from the cognate binding site, is required for transcription factor binding and has implications for bioinformatics searches for novel binding sites. PMID- 26681694 TI - Early postdisaster health outreach to modern families: a cross-sectional study. AB - OBJECTIVES: This study investigated whether the early outreach programme following the Utoya massacre reached out to the parents of the young survivors. Additionally, we explored whether specialised mental healthcare services were provided to parents presenting elevated levels of PTSD and depression reactions. DESIGN: Cross-sectional survey, face-to-face interviews and questionnaires. SETTING: Norway, aftermath of the Utoya massacre, 4-7 months postdisaster. BACKGROUND: Following the Utoya massacre, proactive early outreach programmes were launched in all municipalities that were affected, facilitating access to appropriate healthcare services. PARTICIPANTS: A total of 453 parents of the Utoya survivors aged 13-33 years took part. Overall, 59.8% of the survivors were represented by one or more parent in our study. MAIN OUTCOME MEASURES: Engagement with the proactive early outreach programme (psychosocial crisis teams and contact persons in the municipalities), utilisation of healthcare services (general practitioner and specialised mental healthcare services) and mental distress (UCLA PTSD-RI and HSCL-8). RESULTS: A majority of the participants reported contact with the proactive early outreach programme (crisis team, 73.9%; and contact person, 73.0%). Failure of outreach to parents was significantly associated with non-intact family structure (crisis team: OR 1.69, 95% CI 1.05 to 2.72, p=0.032) and non-Norwegian origin (crisis team: OR 2.39, 95% CI 1.14 to 4.98, p=0.021). Gender of the parent was not significantly associated with failure of the outreach programme (p >= 0.075). Provision of specialised mental healthcare services was significantly associated with higher levels of PTSD (OR 2.08, 95% CI 1.55 to 2.79, p<0.001) and depression (OR 2.42, 95% CI 1.71 to 3.43, p<0.001) and not with the sociodemography (p >= 0.122). CONCLUSIONS: Proactive early outreach strategies may be helpful in identifying healthcare needs and facilitating access to the required services in a population struck by disaster. Our findings prompt increased attention to the complexity of family structures in reaching out universally to modern families following a disaster. PMID- 26681696 TI - The Species versus Subspecies Conundrum: Quantitative Delimitation from Integrating Multiple Data Types within a Single Bayesian Approach in Hercules Beetles. AB - With the recent attention and focus on quantitative methods for species delimitation, an overlooked but equally important issue regards what has actually been delimited. This study investigates the apparent arbitrariness of some taxonomic distinctions, and in particular how species and subspecies are assigned. Specifically, we use a recently developed Bayesian model-based approach to show that in the Hercules beetles (genus Dynastes) there is no statistical difference in the probability that putative taxa represent different species, irrespective of whether they were given species or subspecies designations. By considering multiple data types, as opposed to relying exclusively on genetic data alone, we also show that both previously recognized species and subspecies represent a variety of points along the speciation spectrum (i.e., previously recognized species are not systematically further along the continuum than subspecies). For example, based on evolutionary models of divergence, some taxa are statistically distinguishable on more than one axis of differentiation (e.g., along both phenotypic and genetic dimensions), whereas other taxa can only be delimited statistically from a single data type. Because both phenotypic and genetic data are analyzed in a common Bayesian framework, our study provides a framework for investigating whether disagreements in species boundaries among data types reflect (i) actual discordance with the actual history of lineage splitting, or instead (ii) differences among data types in the amount of time required for differentiation to become apparent among the delimited taxa. We discuss what the answers to these questions imply about what characters are used to delimit species, as well as the diverse processes involved in the origin and maintenance of species boundaries. With this in mind, we then reflect more generally on how quantitative methods for species delimitation are used to assign taxonomic status. PMID- 26681695 TI - Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study. AB - OBJECTIVES: Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke. METHODS: Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR beta-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI. RESULTS: Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2). CONCLUSIONS: This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA. PMID- 26681697 TI - Prevention of neural tube defects in the UK: a missed opportunity. AB - OBJECTIVE: In 1991, the Medical Research Council (MRC) Vitamin Study demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). We aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in the UK from 1998 as it had been in the USA. DESIGN: Estimates of NTD prevalence, the preventive effect of folic acid and the proportion of women taking folic acid supplements before pregnancy were used to predict the number of NTD pregnancies that would have been prevented if folic acid fortification had been implemented. SETTING: Eight congenital anomaly registers in England and Wales. MAIN OUTCOME MEASURES: The prevalence of pregnancies with an NTD in the UK and the number of these pregnancies that would have been prevented if folic acid fortification had been implemented. RESULTS: From 1991 to 2012, the prevalence of NTD pregnancies was 1.28 (95% CI 1.24 to 1.31) per 1000 total births (19% live births, 81% terminations and 0.5% stillbirths and fetal deaths >=20 weeks' gestation). If the USA levels of folic acid fortification from 1998 onwards had been adopted in the UK, an estimated 2014 fewer NTD pregnancies would have occurred. CONCLUSIONS: Failure to implement folic acid fortification in the UK has caused, and continues to cause, avoidable terminations of pregnancy, stillbirths, neonatal deaths and permanent serious disability in surviving children. PMID- 26681698 TI - Behavior Change Fast and Slow: Changing Multiple Key Behaviors a Long-Term Proposition? PMID- 26681699 TI - Pre-eclampsia as Underlying Cause for Perinatal Deaths: Time for Action. PMID- 26681700 TI - Reduced Effectiveness of Contraceptive Implants for Women Taking the Antiretroviral Efavirenz (EFV): Still Good Enough and for How Long? PMID- 26681701 TI - The Levonorgestrel Intrauterine System: Reasons to Expand Access to the Public Sector of Africa. PMID- 26681702 TI - The Levonorgestrel Intrauterine System: A Pragmatic View of an Excellent Contraceptive. PMID- 26681703 TI - The Saturation+ Approach to Behavior Change: Case Study of a Child Survival Radio Campaign in Burkina Faso. AB - A 35-month cluster randomized controlled trial was conducted in Burkina Faso to test whether a radio campaign focused on child health, broadcast between March 2012 and January 2015, could reduce under-5 mortality. This paper describes the design and implementation of the mass media intervention in detail, including the Saturation+ principles that underpinned the approach, the creative process, the lessons learned, and recommendations for implementing this intervention at scale. The Saturation+ approach focuses on the 3 core principles of saturation (ensuring high exposure to campaign messages), science (basing campaign design on data and modeling), and stories (focusing the dramatic climax on the target behavior) to maximize the impact of behavior change campaigns. In Burkina Faso, creative partnerships with local radio stations helped us obtain free airtime in exchange for training and investing in alternative energy supplies to solve frequent energy problems faced by the stations. The campaign used both short spots and longer drama formats, but we consider the short spots as a higher priority to retain during scale-up, as they are more cost-effective than longer formats and have the potential to ensure higher exposure of the population to the messages. The implementation research synthesized in this paper is designed to enable the effective adoption and integration of evidence-based behavior change communication interventions into health care policy and practice. PMID- 26681704 TI - Behavior Change After 20 Months of a Radio Campaign Addressing Key Lifesaving Family Behaviors for Child Survival: Midline Results From a Cluster Randomized Trial in Rural Burkina Faso. AB - BACKGROUND: In Burkina Faso, a comprehensive 35-month radio campaign addressed key, multiple family behaviors for improving under-5 child survival and was evaluated using a repeated cross-sectional, cluster randomized design. The primary outcome of the trial was postneonatal under-5 child mortality. This paper reports on behavior change achieved at midline. METHOD: Fourteen community radio stations in 14 geographic areas were selected based on their high listenership. Seven areas were randomly allocated to receive the intervention while the other 7 areas served as controls. The campaign was launched in March 2012. Cross sectional surveys of about 5,000 mothers of under-5 children, living in villages close to the radio stations, were conducted at baseline (from December 2011 to February 2012) and at midline (in November 2013), after 20 months of campaigning. Statistical analyses were based on cluster-level summaries using a difference-in difference (DiD) approach and adjusted for imbalances between arms at baseline. In addition, routine health facility data were analyzed for evidence of changes in health facility utilization. RESULTS: At midline, 75% of women in the intervention arm reported recognizing radio spots from the campaign. There was some evidence of the campaign having positive effects on care seeking for diarrhea (adjusted DiD, 17.5 percentage points; 95% confidence interval [CI], 2.5 to 32.5; P= .03), antibiotic treatment for fast/difficult breathing (adjusted DiD, 29.6 percentage points; 95% CI, 3.5 to 55.7; P= .03), and saving money during pregnancy (adjusted DiD, 12.8 percentage points; 95% CI, 1.4 to 24.2; P= .03). For other target behaviors, there was little or no evidence of an impact of the campaign after adjustment for baseline imbalances and confounding factors. There was weak evidence of a positive correlation between the intensity of broadcasting of messages and reported changes in target behaviors. Routine health facility data were consistent with a greater increase in the intervention arm than in the control arm in all-cause under-5 consultations (33% versus 17%, respectively), but the difference was not statistically significant (P= .40). CONCLUSION: The radio campaign reached a high proportion of the primary target population, but the evidence for an impact on key child survival-related behaviors at midline was mixed. PMID- 26681705 TI - Barriers to Accessing Emergency Medical Services in Accra, Ghana: Development of a Survey Instrument and Initial Application in Ghana. AB - BACKGROUND: Emergency medical services (EMS) systems provide professional prehospital emergency medical care and transportation to help improve outcomes from emergency conditions. Ghana's national ambulance service has relatively low public utilization in comparison with the large burden of acute disease. METHODS: A survey instrument was developed using Pechansky and Thomas's model of access covering 5 dimensions of availability, accessibility, accommodation, affordability, and acceptability. The instrument was used in a cross-sectional survey in 2013 in Accra, Ghana; eligible participants were those 18 years and older who spoke English, French, or Twi. Although the analysis was mainly descriptive, logistic regression was used to identify factors associated with reported intention to call for an ambulance in the case of a medical emergency. RESULTS: 468 participants completed surveys, with a response rate of 78.4%. Few (4.5%) respondents had ever used an ambulance in prior emergency situations. A substantial proportion (43.8%) knew about the public access medical emergency telephone number, but of those only 37.1% knew it was a toll-free call. Most (54.7%) respondents believed EMTs offered high-quality care, but 78.0% believed taxis were faster than ambulances and 69.2% thought the number of ambulances in Accra insufficient. Many (23.4%) thought using ambulances to transport corpses would be appropriate. In two hypothetical emergency scenarios, respondents most commonly reported taxis as the preferred transportation (63.6% if a family member were burned in a house fire, 64.7% if a pedestrian were struck by a vehicle). About 1 in 5 respondents said they would call an ambulance in either scenario (20.7% if a family member were burned in a house fire, 23.3% if a pedestrian were struck by a vehicle) while 15.5% and 10.2%, respectively, would use any available vehicle. Those aged 18-35 years were more likely than older respondents to prefer an ambulance (odds ratio [OR], 2.27; confidence interval [CI], 1.47 to 3.68), as were those with prior ambulance experience (OR, 1.75; CI, 0.98 to 3.09) (compared with those with no prior experience) and those who believed ambulances were safer than taxis (OR, 2.17; CI, 1.1 to 4.2) (compared with those who did not hold such beliefs). CONCLUSIONS: Perceptions of public ambulance services in Accra, Ghana, are generally favorable, although use is low. Public health education to improve awareness of the toll-free medical emergency number and about appropriate use of ambulances while simultaneously improving the capacity of ambulance agencies to receive increased caseload could improve use of the EMS system. PMID- 26681706 TI - Monitoring and Evaluating the Transition of Large-Scale Programs in Global Health. AB - PURPOSE: Donors are increasingly interested in the transition and sustainability of global health programs as priorities shift and external funding declines. Systematic and high-quality monitoring and evaluation (M&E) of such processes is rare. We propose a framework and related guiding questions to systematize the M&E of global health program transitions. METHODS: We conducted stakeholder interviews, searched the peer-reviewed and gray literature, gathered feedback from key informants, and reflected on author experiences to build a framework on M&E of transition and to develop guiding questions. FINDINGS: The conceptual framework models transition as a process spanning pre-transition and transition itself and extending into sustained services and outcomes. Key transition domains include leadership, financing, programming, and service delivery, and relevant activities that drive the transition in these domains forward include sustaining a supportive policy environment, creating financial sustainability, developing local stakeholder capacity, communicating to all stakeholders, and aligning programs. Ideally transition monitoring would begin prior to transition processes being implemented and continue for some time after transition has been completed. As no set of indicators will be applicable across all types of health program transitions, we instead propose guiding questions and illustrative quantitative and qualitative indicators to be considered and adapted based on the transition domains identified as most important to the particular health program transition. The M&E of transition faces new and unique challenges, requiring measuring constructs to which evaluators may not be accustomed. Many domains hinge on measuring "intangibles" such as the management of relationships. Monitoring these constructs may require a compromise between rigorous data collection and the involvement of key stakeholders. CONCLUSION: Monitoring and evaluating transitions in global health programs can bring conceptual clarity to the transition process, provide a mechanism for accountability, facilitate engagement with local stakeholders, and inform the management of transition through learning. Further investment and stronger methodological work are needed. PMID- 26681707 TI - Sexual Satisfaction, Performance, and Partner Response Following Voluntary Medical Male Circumcision in Zambia: The Spear and Shield Project. AB - BACKGROUND: Voluntary medical male circumcision (VMMC) is an important HIV prevention strategy, particularly in regions with high HIV incidence and low rates of male circumcision. However, 88% of the Zambian male population remain uncircumcised, and of these 80% of men surveyed expressed little interest in undergoing VMMC. METHODS: The Spear and Shield study (consisting of 4 weekly, 90 minute sexual risk reduction/VMMC promotion sessions) recruited and enrolled men (N = 800) who self-identified as at risk of HIV by seeking HIV testing and counseling at community health centers. Eligible men tested HIV-negative, were uncircumcised, and expressed no interest in VMMC. Participants were encouraged (but not required) to invite their female partners (N = 668) to participate in the program in a gender-concordant intervention matched to their partners'. Men completed assessments at baseline, post-intervention (about 2 months after baseline), and 6 and 12 months post-intervention; women completed assessments at baseline and post-intervention. For those men who underwent VMMC and for their partners, an additional assessment was conducted 3 months following the VMMC. The ancillary analysis in this article compared the pre- and post-VMMC responses of the 257 Zambian men who underwent circumcision during or following study participation, using growth curve analyses, as well as of the 159 female partners. RESULTS: Men were satisfied overall with the procedure (mean satisfaction score, 8.4 out of 10), and nearly all men (96%) and women (94%) stated they would recommend VMMC to others. Approximately half of the men reported an increase or no change in erections, orgasms, and time to achieve orgasms from pre-VMMC, while one-third indicated fewer erections and orgasms and decreased time to achieve orgasms post-VMMC. Nearly half (42%) of the men, and a greater proportion (63%) of the female partners, said their sexual pleasure increased while 22% of the men reported less sexual pleasure post-VMMC. Growth curve analysis of changes in sexual functioning and satisfaction over time revealed no changes in erectile functioning or intercourse satisfaction, but there were increases in orgasm functioning, overall sexual satisfaction, and sexual desire. The majority (61% to 70%) of men and women thought penile cleanliness and appearance had improved post-VMMC. Of the 69% of men who reported having sexual intercourse at least once between having the procedure and their 3 month post-VMMC assessment, the large majority (76%) waited at least 6 weeks before resuming sex. Sexual intercourse prior to the 6-week healing period was associated with adverse events and lower levels of post-VMMC sexual satisfaction. CONCLUSION: Both men and their partners can generally expect equal or improved sexual satisfaction and penile hygiene following VMMC. Future studies should consider innovative strategies to assist men in their efforts to abstain from sexual activities prior to complete healing. PMID- 26681708 TI - Reducing Motor Vehicle-Related Injuries at an Arizona Indian Reservation: Ten Years of Application of Evidence-Based Strategies. AB - Unintentional injury is a significant public health burden for American Indians and Alaska Natives and was the leading cause of death among those aged 1 to 44 years between 1999 and 2004. Of those deaths, motor vehicle-related deaths cause the most mortality, justifying the need for intervention at an American Indian Reservation in Arizona (United States). We describe motor vehicle injury prevention program operations from 2004 through 2013. This community-based approach led by a multidisciplinary team primarily comprised of environmental public health and law enforcement personnel implemented evidence-based strategies to reduce the impact of motor vehicle-related injuries and deaths, focusing on reducing impaired driving and increasing occupant restraint use. Strategies included: mass media campaigns to enhance awareness and outreach; high-visibility sobriety checkpoints; passing and enforcing 0.08% blood alcohol concentration limits for drivers and primary occupant restraint laws; and child car seat distribution and education. Routine monitoring and evaluation data showed a significant 5% to 7% annual reduction of motor vehicle crashes (MVCs), nighttime MVCs, MVCs with injuries/fatalities, and nighttime MVCs with injuries/fatalities between 2004 and 2013, but the annual percent change in arrests for driving under the influence (DUI) was not significant. There was also a 144% increase in driver/front seat passenger seat belt use, from 19% in 2011 before the primary occupant restraint law was enacted to 47% during the first full year of enforcement (2013). Car seat checkpoint data also suggested a 160% increase in car seat use, from less than 20% to 52% in 2013. Implementation of evidence-based strategies in injury prevention, along with employment of key program approaches such as strong partnership building, community engagement, and consistent staffing and funding, can narrow the public health disparity gap experienced among American Indian and Alaska Native communities. PMID- 26681709 TI - Family Planning Supply Environment in Kinshasa, DRC: Survey Findings and Their Value in Advancing Family Planning Programming. AB - BACKGROUND: Modern contraceptive prevalence was 14.1% in 2007 in Kinshasa, the capital city of the Democratic Republic of the Congo (DRC). Yet virtually nothing was known about the family planning supply environment. METHODS: Three surveys of health facilities were conducted in 2012, 2013, and 2014 to determine the number, spatial distribution, and attributes of sites providing family planning services. The 2012 and 2013 surveys aimed to identify the universe of family planning facilities while obtaining a limited set of data on "readiness" to provide family planning services (defined as having at least 3 modern methods, at least 1 person training in family planning in the last 3 years, and an information system to track distribution of products to clients) and output (measured by couple-years of protection, or CYP). In contrast, the 2014 survey, conducted under the umbrella of the Performance Monitoring and Accountability 2020 (PMA2020) project, was based on 2-stage cluster sampling. This article provides detailed analysis of the 2012 and 2013 surveys, including bivariate and multivariate analysis of correlates of readiness to provide services and of output. RESULTS: We identified 184 health facilities that reported providing at least 1 contraceptive method in 2012 and 395 facilities in 2013. The percentage of sites defined as "ready" to provide services increased from 44.1% in 2012 to 63.3% in 2013. For the 3-month period between January and March 2013, facilities distributed between 0 and 879.2 CYP (mean, 39.7). Nearly half (49%) of the CYP was attributable to implants, followed by IUDs (24%), CycleBeads (11%), and injectables (8%). In 2013, facilities supported by PEPFAR (n = 121) were more likely than other facilities to be rated as ready to provide services (P<.0001); however, PEPFAR-supported sites generated less CYP on average than sites supported by family planning implementing agencies (P<.0001). Multivariate analysis showed 3 variables were associated with CYP: type of health facility, length of time in operation, and number of contraceptive methods available. Clinics generated higher (3-month) CYP than hospitals and health centers by 65.3 and 61.5 units, respectively (P<.01). The mean CYP for facilities in operation for 4-6 years was 26.9 units higher (P<.05), and 50.2 units higher for those operating 7+ years (P<.01), than the reference group of facilities in operation for 1 year or less. For each additional method available at a facility, CYP increased by almost 8 units (P<.01). CONCLUSIONS: Findings from these surveys suggest that lack of physical access is not the defining reason for low contraceptive use in Kinshasa, although it is highly likely that other service-related factors contribute to low service utilization. The results contributed to increasing the momentum for family planning in the DRC in many ways, including mobilizing partners to increase contraceptive access and increasing donor investment in family planning in the DRC. PMID- 26681710 TI - Introduction of Mobile Health Tools to Support Ebola Surveillance and Contact Tracing in Guinea. AB - Challenges in data availability and quality have contributed to the longest and deadliest Ebola epidemic in history that began in December 2013. Accurate surveillance data, in particular, has been difficult to access, as it is often collected in remote communities. We describe the design, implementation, and challenges of implementing a smartphone-based contact tracing system that is linked to analytics and data visualization software as part of the Ebola response in Guinea. The system, built on the mobile application CommCare and business intelligence software Tableau, allows for real-time identification of contacts who have not been visited and strong accountability of contact tracers through timestamps and collection of GPS points with their surveillance data. Deployment of this system began in November 2014 in Conakry, Guinea, and was expanded to a total of 5 prefectures by April 2015. To date, the mobile system has not replaced the paper-based system in the 5 prefectures where the program is active. However, as of April 30, 2015, 210 contact tracers in the 5 prefectures were actively using the mobile system to collectively monitor 9,162 contacts. With proper training, some investment in technical hardware, and adequate managerial oversight, there is opportunity to improve access to surveillance data from difficult-to-reach communities in order to inform epidemic control strategies while strengthening health systems to reduce risk of future disease outbreaks. PMID- 26681711 TI - Nurse Mentors to Advance Quality Improvement in Primary Health Centers: Lessons From a Pilot Program in Northern Karnataka, India. AB - High-quality care during labor, delivery, and the postpartum period is critically important since maternal and child morbidity and mortality are linked to complications that arise during these stages. A nurse mentoring program was implemented in northern Karnataka, India, to improve quality of services at primary health centers (PHCs), the lowest level in the public health system that offers basic obstetric care. The intervention, conducted between August 2012 and July 2014, employed 53 full-time nurse mentors and was scaled-up in 385 PHCs in 8 poor rural districts. Each mentor was responsible for 6 to 8 PHCs and conducted roughly 6 mentoring visits per PHC in the first year. This paper reports the results of a qualitative inquiry, conducted between September 2012 and April 2014, assessing the program's successes and challenges from the perspective of mentors and PHC teams. Data were gathered through 13 observations, 9 focus group discussions with mentors, and 25 individual and group interviews with PHC nurses, medical officers, and district health officers. Mentors and PHC staff and leaders reported a number of successes, including development of rapport and trust between mentors and PHC staff, introduction of team-based quality improvement processes, correct and consistent use of a new case sheet to ensure adherence to clinical guidelines, and increases in staff nurses' knowledge and skills. Overall, nurses in many PHCs reported an increased ability to provide care according to guidelines and to handle maternal and newborn complications, along with improvements in equipment and supplies and referral management. Challenges included high service delivery volumes and/or understaffing at some PHCs, unsupportive or absent PHC leadership, and cultural practices that impacted quality. Comprehensive mentoring can build competence and improve performance by combining on-the-job clinical and technical support, applying quality improvement principles, and promoting team-based problem solving. PMID- 26681713 TI - Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA RENAL): A Randomized Clinical Trial. AB - OBJECTIVE: Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment. RESEARCH DESIGN AND METHODS: In this 26-week, double-blind trial, 279 patients with HbA1c 7-10%, BMI 20-45 kg/m(2), and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2); MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139). RESULTS: The estimated treatment difference in HbA1c from baseline to week 26 was -0.66% ( 7.25 mmol/mol) (95% CI -0.90 to -0.43 [-9.82 to -4.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (-1.22 mmol/L [-22.0 mg/dL]) than with placebo (-0.57 mmol/L [-10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (-2.41 kg) than with placebo (-1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: -1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P < 0.0001). CONCLUSIONS: Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment. PMID- 26681712 TI - Racial Differences in and Prognostic Value of Biomarkers of Hyperglycemia. AB - OBJECTIVE: We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5 anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. RESEARCH DESIGN AND METHODS: We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. RESULTS: Median values of biomarkers were higher among blacks versus whites (all P < 0.001). Relative risks for each biomarker with incident CVD and ESRD, and odds ratios for each biomarker with prevalent retinopathy, were similar by race (all P values for interaction by race >0.10). CONCLUSIONS: The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications. PMID- 26681714 TI - Adherence to Oral Glucose-Lowering Therapies and Associations With 1-Year HbA1c: A Retrospective Cohort Analysis in a Large Primary Care Database. AB - OBJECTIVE: The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS: Data were extracted for patients treated between 2004 and 2014 who were newly prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase 4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio >=0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS: In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4 mmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS: Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use. PMID- 26681715 TI - Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies. AB - OBJECTIVE: Type 2 diabetes pathophysiology is characterized by dysregulated glucagon secretion. LY2409021, a potent, selective small-molecule glucagon receptor antagonist that lowers glucose was evaluated for efficacy and safety in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The efficacy (HbA1c and glucose) and safety (serum aminotransferase) of once-daily oral administration of LY2409021 was assessed in two double-blind studies. Phase 2a study patients were randomized to 10, 30, or 60 mg of LY2409021 or placebo for 12 weeks. Phase 2b study patients were randomized to 2.5, 10, or 20 mg LY2409021 or placebo for 24 weeks. RESULTS: LY2409021 produced reductions in HbA1c that were significantly different from placebo over both 12 and 24 weeks. After 12 weeks, least squares (LS) mean change from baseline in HbA1c was -0.83% (10 mg), -0.65% (30 mg), and -0.66% (60 mg) (all P < 0.05) vs. placebo, 0.11%. After 24 weeks, LS mean change from baseline in HbA1c was -0.45% (2.5 mg), -0.78% (10 mg, P < 0.05), -0.92% (20 mg, P < 0.05), and -0.15% with placebo. Increases in serum aminotransferase, fasting glucagon, and total fasting glucagon-like peptide-1 (GLP-1) were observed; levels returned to baseline after drug washout. Fasting glucose was also lowered with LY2409021 at doses associated with only modest increases in aminotransferases (mean increase in alanine aminotransferase [ALT] <=10 units/L). The incidence of hypoglycemia in the LY2409021 groups was not statistically different from placebo. CONCLUSIONS: In patients with type 2 diabetes, glucagon receptor antagonist treatment significantly lowered HbA1c and glucose levels with good overall tolerability and a low risk for hypoglycemia. Modest, reversible increases in serum aminotransferases were observed. PMID- 26681716 TI - A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study. AB - OBJECTIVE: Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA. RESEARCH DESIGN AND METHODS: Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 +/- 10 years [mean +/- SD], BMI 27.6 +/- 4.5 kg/m(2)). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: >=5.7% (39 mmol/mol) (range 4.2-6.6% [22.4-48.6 mmol/mol]), >=230 umol/L (range 161-269 umol/L), and >=13.35% (range 10.20-16.07%), respectively. RESULTS: Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both >0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P < 0.001). CONCLUSIONS: As individual tests, A1C, fructosamine, and GA detected <=50% of Africans with prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes. PMID- 26681717 TI - Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes. AB - OBJECTIVE: We investigated fat distribution and tissue-specific insulin stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. RESEARCH DESIGN AND METHODS: A total of 23 obese patients (BMI 43.0 +/- 3.6 kg/m(2); 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [(18)F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. RESULTS: At baseline, visceral fat GU was 30 +/- 7% of muscle GU in control subjects and 57 +/- 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (~40%) more than subcutaneous fat (7%). Tissue specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. CONCLUSIONS: Bariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose. PMID- 26681718 TI - Effects of GLP-1 Receptor Agonists on Heart Rate and the Autonomic Nervous System Using Holter Electrocardiography and Power Spectrum Analysis of Heart Rate Variability. PMID- 26681719 TI - Weight Change-Adjusted Effects of Gastric Bypass Surgery on Glucose Metabolism: 2 and 10-Year Results From the Swedish Obese Subjects (SOS) Study. AB - OBJECTIVE: It has been suggested that weight change-independent effects on fasting insulin and glucose levels are present after gastric bypass (GBP) but not after banding and vertical banded gastroplasty (VBG). We therefore evaluated weight change-adjusted effects of GBP, compared with restrictive surgical procedures, on long-term changes in fasting levels of glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the Swedish Obese Subjects (SOS) study. RESEARCH DESIGN AND METHODS: Participants who completed the 2-year (n = 1,762) and/or the 10-year (n = 1,216) follow-up were divided into three weight change classes (weight loss >30%, 20-30%, or <=20%), and by surgical method (banding, VBG, or GBP). Glucose, insulin, and HOMA-IR changes were analyzed in relation to weight change over 2 and 10 years. Analyses were performed in the full cohort and also in subgroups based on baseline glucose status. RESULTS: Within weight change classes, reductions in glucose, insulin, and HOMA-IR were similar in the three surgery groups both at 2 and at 10 years. Reductions in glucose, insulin, and HOMA-IR increased with increasing weight loss, and changes were typically related to weight change within each surgery group. Moreover, the association between weight change and change in glucose, insulin, or HOMA-IR did not differ between the surgery groups at 2 and 10 years. When patients were subdivided also by baseline glucose status, similar relationships between weight changes and changes in glucose, insulin, and HOMA-IR were observed. CONCLUSIONS: Even though weight loss-independent effects are important for short-term diabetes remission, our results suggest that degree of weight loss is more important for long-term reductions in fasting insulin and glucose than choice of bariatric surgery procedure. PMID- 26681720 TI - Cardiovascular and Other Outcomes Postintervention With Insulin Glargine and Omega-3 Fatty Acids (ORIGINALE). AB - OBJECTIVE: The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial reported neutral effects of insulin glargine on cardiovascular outcomes and cancers and reduced incident diabetes in high-cardiovascular risk adults with dysglycemia after 6.2 years of active treatment. Omega-3 fatty acids had neutral effects on cardiovascular outcomes. The ORIGIN and Legacy Effects (ORIGINALE) study measured posttrial effects of these interventions during an additional 2.7 years. RESEARCH DESIGN AND METHODS: Surviving ORIGIN participants attended up to two additional visits. The hazard of clinical outcomes during the entire follow up period from randomization was calculated. RESULTS: Of 12,537 participants randomized, posttrial data were analyzed for 4,718 originally allocated to insulin glargine (2,351) versus standard care (2,367), and 4,771 originally allocated to omega-3 fatty acid supplements (2,368) versus placebo (2,403). Posttrial, small differences in median HbA1c persisted (glargine 6.6% [49 mmol/mol], standard care 6.7% [50 mmol/mol], P = 0.025). From randomization to the end of posttrial follow-up, no differences were found between the glargine and standard care groups in myocardial infarction, stroke, or cardiovascular death (1,185 vs. 1,165 events; hazard ratio 1.01 [95% CI 0.94-1.10]; P = 0.72); myocardial infarction, stroke, cardiovascular death, revascularization, or hospitalization for heart failure (1,958 vs. 1,910 events; 1.03 [0.97-1.10]; P = 0.38); or any cancer (524 vs. 529 events; 0.99 [0.88-1.12]; P = 0.91) or between omega-3 and placebo groups in cardiovascular death (688 vs. 700; 0.98 [0.88 1.09]; P = 0.68) or other outcomes. CONCLUSIONS: During >6 years of treatment followed by >2.5 years of observation, insulin glargine had neutral effects on health outcomes and salutary effects on metabolic control, whereas omega-3 fatty acid supplementation had no effect. PMID- 26681721 TI - Risk Factors Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes. AB - OBJECTIVE: Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence. RESEARCH DESIGN AND METHODS: A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were >=60 years old with type 1 diabetes for >=20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics. RESULTS: Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels <60 mg/dL for >=20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects. CONCLUSIONS: In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed. PMID- 26681722 TI - Potato Consumption and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies. AB - OBJECTIVE: We aimed to elucidate whether potato consumption is associated with a higher risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We analyzed data in three cohorts consisting of U.S. male and female health professionals without diabetes, cardiovascular disease, and cancer at baseline: 70,773 women from the Nurses' Health Study (1984-2010), 87,739 women from Nurses' Health Study II (1991-2011), and 40,669 men from the Health Professionals Follow-up Study (1986-2010). Potato consumption was assessed quadrennially using validated food frequency questionnaires (FFQs), and we calculated 4-year change in potato consumption from consecutive FFQs. Self-reported T2D diagnosis was confirmed using a validated supplementary questionnaire. RESULTS: During 3,988,007 person years of follow-up, 15,362 new cases of T2D were identified. Higher consumption of total potatoes (including baked, boiled, or mashed potatoes and french fries) was significantly associated with an elevated risk for T2D: the pooled hazard ratio (HR) of T2D compared with <1 serving/week was 1.07 (95% CI 0.97-1.18) for 2 4 servings/week and 1.33 (95% CI 1.17-1.52) for >=7 servings/week after adjustment for demographic, lifestyle, and dietary factors. In addition, the pooled HRs of T2D for every 3 servings/week were 1.04 (95% CI 1.01-1.08) for baked, boiled, or mashed potatoes, and 1.19 (95% CI 1.13-1.25) for french fries. We further estimated that the HR of T2D was 0.88 (95% CI 0.84-0.91) for replacing 3 servings/week of total potatoes with the same amount of whole grains. Last, in comparison with stable potato consumption, every 3-servings/week increment of potato consumption in 4 years was associated with a 4% (95% CI 0-8%) higher T2D risk. CONCLUSIONS: Greater consumption of potatoes, especially french fries, was associated with a higher T2D risk, independent of BMI and other risk factors. Replacement of potatoes with whole grains was associated with a lower T2D risk. PMID- 26681723 TI - Celiac Disease Increases Risk of Thyroid Disease in Patients With Type 1 Diabetes: A Nationwide Cohort Study. AB - OBJECTIVE: Both type 1 diabetes (T1D) and celiac disease (CD) have been linked to autoimmune thyroid disease (ATD). We examined if individuals with both T1D and CD were at a higher risk of ATD than those with only T1D. RESEARCH DESIGN AND METHODS: This study was a nationwide population-based cohort study. We defined T1D as having an inpatient or a hospital-based outpatient diagnosis of T1D at age <=30 years in the Swedish National Patient Register between 1964 and 2009. Data on CD were obtained through small intestinal biopsy reports showing villous atrophy (Marsh histopathology grade III) between 1969 and 2008 at any of the 28 pathology departments in Sweden. ATD included hyperthyreosis and hypothyreosis, defined according to the Swedish National Patient Register. We identified 947 individuals with T1D and biopsy-verified CD. These were matched to 4,584 control subjects with T1D but no CD diagnosis. Cox regression then estimated the risk of ATD. RESULTS: Among T1D, CD was a risk factor for later ATD. During follow-up, 90 T1D+CD patients developed ATD (expected n = 54). Adjusting for sex, age, and calendar period, this corresponded to a hazard ratio (HR) of 1.67 (95% CI 1.32 2.11; P < 0.001). This excess risk was highest in those who had CD for 10 years or more (HR 2.22 [95% CI 1.49-3.23]). Risk increases were seen in both males and females. CD was a risk factor for both hypothyreosis (HR 1.66 [95% CI 1.30-2.12]) and hyperthyreosis (HR 1.72 [95% CI 0.95-3.11]). CONCLUSIONS: Among patients with T1D, CD is a risk factor for the later development of ATD. PMID- 26681724 TI - Health Care Transition in Young Adults With Type 1 Diabetes: Perspectives of Adult Endocrinologists in the U.S. AB - OBJECTIVE: Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. Our objective was to describe experiences, resources, and barriers reported by a national sample of adult endocrinologists receiving and caring for young adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: We fielded an electronic survey to adult endocrinologists with a valid e-mail address identified through the American Medical Association Physician Masterfile. RESULTS: We received responses from 536 of 4,214 endocrinologists (response rate 13%); 418 surveys met the eligibility criteria. Respondents (57% male, 79% Caucasian) represented 47 states; 64% had been practicing >10 years and 42% worked at an academic center. Only 36% of respondents reported often/always reviewing pediatric records and 11% reported receiving summaries for transitioning young adults with type 1 diabetes, although >70% felt that these activities were important for patient care. While most respondents reported easy access to diabetes educators (94%) and dietitians (95%), fewer (42%) reported access to mental health professionals, especially in nonacademic settings. Controlling for practice setting and experience, endocrinologists without easy access to mental health professionals were more likely to report barriers to diabetes management for young adults with depression (odds ratio [OR] 5.3; 95% CI 3.4, 8.2), substance abuse (OR 3.5; 95% CI 2.2, 5.6), and eating disorders (OR 2.5; 95% CI 1.6, 3.8). CONCLUSIONS: Our findings underscore the need for enhanced information transfer between pediatric and adult providers and increased mental health referral access for young adults with diabetes post-transition. PMID- 26681725 TI - Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. AB - OBJECTIVE: Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS: At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 +/- 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to >=70 mg/dL or >=20 mg/dL from the glucose nadir within 30 min after receiving glucagon. RESULTS: Mean plasma glucose at time of glucagon administration was 48 +/- 8 and 49 +/- 8 mg/dL at the intranasal and intramuscular visits, respectively. Success criteria were met at all but one intranasal visit and at all intramuscular visits (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P < 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively. CONCLUSIONS: Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response. PMID- 26681726 TI - Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005-2011. AB - OBJECTIVE: Appropriate glycemic control is fundamental to diabetes care, but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia. We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. RESEARCH DESIGN AND METHODS: This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) network sites. Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age, sex, comorbidity status, antecedent A1C level, and medication use. RESULTS: Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years. Rates of severe hypoglycemia were higher among those with older age, chronic kidney disease, congestive heart failure, cardiovascular disease, depression, and higher A1C levels, and in users of insulin, insulin secretagogues, or beta-blockers (P < 0.001 for all). Changes in severe hypoglycemia occurrence over time were not clinically significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease, congestive heart failure, and cardiovascular disease. CONCLUSIONS: Risk of severe hypoglycemia in clinical settings is considerably higher in identifiable patient subgroups than in randomized controlled trials. Strategies that reduce the risk of hypoglycemia in high-risk patients are needed. PMID- 26681728 TI - Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population, 2002-2013. AB - OBJECTIVE: To estimate the prevalence of diabetes and diabetic nephropathy in a large population of U.S. commercially insured patients aged <18 years from 2002 to 2013. RESEARCH DESIGN AND METHODS: Using the U.S. MarketScan Commercial Claims and Encounters Database, we identified 96,171 pediatric patients with diabetes and 3,161 pediatric patients with diabetic nephropathy during 2002-2013. We estimated prevalence of pediatric diabetes overall, by diabetes type, age, and sex, and prevalence of pediatric diabetic nephropathy overall, by age, sex, and diabetes type. RESULTS: The annual prevalence of diabetes in the whole pediatric population increased from 1.86 to 2.82 per 1,000 during 2002-2013: 1.48 to 2.32 per 1,000 for type 1 diabetes and 0.38 to 0.67 per 1,000 for type 2 diabetes in 2002-2006 and then 0.56 to 0.49 per 1,000 thereafter. The annual prevalence of diabetic nephropathy in pediatric patients with diabetes increased from 1.16 to 3.44% for all cases and 0.83 to 2.32% for probable cases only in 2002-2013. Prevalence of diabetes and diabetic nephropathy was highest in patients aged 12 to <18 years. While prevalence of type 1 diabetes was higher in male than in female youth, prevalence of type 2 diabetes and diabetic nephropathy was higher in female than in male youth. There was no difference in prevalence of diabetic nephropathy by diabetes type. CONCLUSIONS: The prevalence of diabetes and diabetic nephropathy increased in the U.S. MarketScan commercially insured pediatric population from 2002 to 2013. The prevalence of diabetes and diabetic nephropathy markedly increased starting at age 12 years. PMID- 26681727 TI - Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia. AB - OBJECTIVE: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random effects meta-analyses. RESULTS: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001). CONCLUSIONS: Individuals with type 2 diabetes are at ~60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women. PMID- 26681729 TI - Effect of high salt diet on blood pressure and renal damage during vascular endothelial growth factor inhibition with sunitinib. AB - BACKGROUND: Antiangiogenic treatment with the multitargeted vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib associates with a blood pressure (BP) rise and glomerular renal injury. Recent evidence indicates that VEGF derived from tubular cells is required for maintenance of the peritubular vasculature. In the present study, we focussed on tubular and glomerular pathology induced by sunitinib and explored whether a high salt (HS) diet augments the BP rise and renal abnormalities. METHODS: Normotensive Wistar Kyoto (WKY) rats were exposed to a normal salt (NS) or HS diet for 2 weeks and subsequently for 8 days to sunitinib or vehicle administration after which the rats were euthanized and kidneys excised. Mean arterial pressure (MAP) was telemetrically measured. Urine was sampled for proteinuria and endothelinuria, and blood for measurement of endothelin-1, creatinine and cystatin C. RESULTS: Compared with the NS diet, MAP rapidly rose by 27 +/- 3 mmHg with the HS diet. On sunitinib, MAP rose further by 15 +/- 1 with the NS and by 23 +/- 4 mmHg with the HS diet (P < 0.05). The HS diet itself had no effect on proteinuria, endothelinuria or the plasma levels of endothelin-1, creatinine and cystatin C. Only with the HS diet, sunitinib administration massively increased proteinuria and endothelinuria and these two parameters were related (r = 0.50, P < 0.01). Likewise, renal glomerular pathology was enhanced during sunitinib with the HS diet, whereas tubulointerstitial injury or reduced peritubular capillary density did not occur. CONCLUSIONS: An HS diet induces a marked BP rise in WKY rats and exacerbates both the magnitude of the BP rise and glomerular injury induced by sunitinib. PMID- 26681730 TI - Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease: results of the TEMPO 3:4 Trial. AB - BACKGROUND: The TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable. METHODS: Post hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients. Albuminuria was measured in a spot morning urine sample prior to tolvaptan dosing and expressed as albumin-to creatinine ratio (ACR). RESULTS: Baseline median (interquartile range) ACR was 3.2 (1.7-7.1) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR. Subjects with higher baseline ACR had higher blood pressure and total kidney volume (TKV) and lower estimated glomerular filtration rate (eGFR). During follow-up, higher baseline ACR was associated with more rapid eGFR loss (P < 0.0001 for trend), but not with rate of growth in TKV. During the 3-year trial, ACR rose in placebo- and decreased in tolvaptan-treated patients (+0.23 versus -0.40 mg/mmol). The difference ACR increased over time, reaching a maximum of 24% at Month 36 (P < 0.001). At that time only a minor difference in blood pressure was observed (mean arterial pressure -1.9 mmHg for tolvaptan). The decrease in ACR was similar in all subgroups investigated, and remained after withdrawal of study drug. The beneficial effect of tolvaptan on TKV growth and eGFR loss was stronger in patients with higher baseline ACR. CONCLUSIONS: In ADPKD, higher baseline albuminuria was associated with more eGFR loss. Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure. Treatment efficacy of tolvaptan on changes in TKV and eGFR was more readily detected in patients with higher albuminuria. PMID- 26681732 TI - Risk factors for progressive polycystic liver disease: where do we stand? PMID- 26681731 TI - Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. AB - BACKGROUND: In chronic kidney disease (CKD), serum concentrations of fibroblast growth factor 23 (FGF23) increase progressively as glomerular filtration rate declines, while renal expression of the FGF23 coreceptor Klotho decreases. Elevated circulating FGF23 levels are strongly associated with mortality and with left ventricular hypertrophy (LVH), which is a major cause of cardiovascular death in CKD patients. The cardiac FGF23/FGF receptor (FGFR) system and its role in the development of LVH in humans have not been addressed previously. METHODS: We conducted a retrospective case-control study in 24 deceased patients with childhood-onset end-stage renal disease (dialysis: n = 17; transplanted: n = 7), and 24 age- and sex-matched control subjects. Myocardial autopsy samples of the left ventricle were evaluated for expression of endogenous FGF23, FGFR isoforms, Klotho, calcineurin and nuclear factor of activated T-cells (NFAT) by immunohistochemistry, immunofluorescence microscopy, qRT-PCR and western blotting. RESULTS: The majority of patients presented with LVH (67%). Human cardiomyocytes express full-length FGF23, and cardiac FGF23 is excessively high in patients with CKD. Enhanced myocardial expression of FGF23 in concert with Klotho deficiency strongly correlates with the presence of LVH. Cardiac FGF23 levels associate with time-averaged serum phosphate levels, up-regulation of FGFR4 and activation of the calcineurin-NFAT signaling pathway, an established mediator of cardiac remodelling and LVH. These changes are detected in patients on dialysis but not in those with a functioning kidney transplant. CONCLUSIONS: Our results indicate a strong association between LVH and enhanced expression levels of FGF23, FGFR4 and calcineurin, activation of NFAT and reduced levels of soluble Klotho in the myocardium of patients with CKD. These alterations are not observed in kidney transplant patients. PMID- 26681733 TI - Primary care physicians' perceived barriers, facilitators and strategies to enhance conservative care for older adults with chronic kidney disease: a qualitative descriptive study. AB - BACKGROUND: Although primary care physicians (PCPs) are often responsible for the routine care of older adults with chronic kidney disease (CKD), there is a paucity of evidence regarding their perspectives and practice of conservative (non-dialysis) care. We undertook a qualitative study to describe barriers, facilitators and strategies to enhance conservative, non-dialysis, CKD care by PCPs in the community. METHODS: Semi-structured telephone and face-to-face interviews were conducted with PCPs from Alberta, Canada. Participants were identified using a snowball sampling strategy and purposively sampled based on sex, age and rural/urban location of clinical practice. Eligible participants had managed at least one patient >=75 years with Stage 5 CKD (estimated glomerular filtration rate <15 mL/min/1.73 m2, not on dialysis) in the prior year. Participant recruitment ceased when data saturation was reached. Transcripts were analyzed thematically using conventional content analysis. RESULTS: In total, 27 PCPs were interviewed. The majority were male (15/27), were aged 40-60 years (15/27) and had practiced in primary care for >20 years (14/27). Perceived barriers to conservative CKD care included: managing expectations of kidney failure for patients and their families; dealing with the complexity of medical management of patients requiring conservative care; and challenges associated with managing patients jointly with specialists. Factors that facilitated conservative CKD care included: establishing patient/family expectations early; preserving continuity of care; and utilizing a multidisciplinary team approach. Suggested strategies for improving conservative care included having: direct telephone access to clinicians familiar with conservative care; treatment decision aids for patients and their families; and a conservative care clinical pathway to guide management. CONCLUSIONS: PCPs identified important barriers and facilitators to conservative care for their older patients with Stage 5 CKD. Further investigation of potential strategies that address barriers and enable facilitators is required to improve the quality of conservative care for older adults in the community. PMID- 26681734 TI - Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica. AB - A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core -> 3)-beta-D-GalNAc-(1 -> 4)-beta-D-GlcA-(1 ->. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ~ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin. PMID- 26681735 TI - Distress Tolerance: Associations With Posttraumatic Stress Disorder Symptoms Among Trauma-Exposed, Cocaine-Dependent Adults. AB - The present investigation examined associations between distress tolerance and posttraumatic stress disorder (PTSD) symptoms in a cocaine-dependent sample. Participants were comprised of 138 cocaine-dependent adults (Mage = 45.4, SD = 9.9; 81% male; 76.3% African American) who endorsed trauma exposure, defined according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) PTSD Criterion A. Participants were administered interview-based measures and completed a series of self-report questionnaires. Results indicated that distress tolerance was significantly, incrementally (negatively) associated with PTSD symptom severity, contributing 6.8% of unique variance to the model (p < .001); notably, the overall model explained 44.8% of variance in PTSD symptomatology. Distress tolerance also contributed between 2.7% and 6.8% of unique variance across each of the PTSD symptom clusters (ps < .05). Incremental effects were documented, after accounting for the variance explained by theoretically relevant covariates (i.e., gender, cocaine-use severity, depressive symptoms, trauma-exposure severity). Theoretical and clinical implications are discussed. PMID- 26681738 TI - ESR1 Mutations Prevalent in Some Breast Cancers. AB - A recent analysis of cell-free DNA from blood samples found that ESR1 mutations are highly prevalent and associated with worse overall survival in women with advanced estrogen receptor-positive breast cancer that progressed on aromatase inhibitor therapy. The data also show that patients' mutation status may affect their response to the mTOR inhibitor everolimus. PMID- 26681739 TI - Tracing Melanoma's Genetic Progression. AB - New research that traces melanoma's genetic progression shows that different lesion types have distinctive mutations. The study also bolsters the evidence for an intermediate category of lesions between benign nevi and malignant disease. PMID- 26681736 TI - Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism. AB - The cytochrome P450 (P450) enzymes are the predominant enzyme system involved in human drug metabolism. Alterations in the expression and/or activity of these enzymes result in changes in pharmacokinetics (and consequently the pharmacodynamics) of drugs that are metabolized by this set of enzymes. Apart from changes in activity as a result of drug-drug interactions (by P450 induction or inhibition), the P450 enzymes can exhibit substantial interindividual variation in basal expression and/or activity, leading to differences in the rates of drug elimination and response. This interindividual variation can result from a myriad of factors, including genetic variation in the promoter or coding regions, variation in transcriptional regulators, alterations in microRNA that affect P450 expression, and ontogenic changes due to exposure to xenobiotics during the developmental and early postnatal periods. Other than administering a probe drug or cocktail of drugs to obtain the phenotype or conducting a genetic analysis to determine genotype, methods to determine interindividual variation are limited. Phenotyping via a probe drug requires exposure to a xenobiotic, and genotyping is not always well correlated with phenotype, making both methodologies less than ideal. This article describes recent work evaluating the effect of some of these factors on interindividual variation in human P450 mediated metabolism and the potential utility of endogenous probe compounds to assess rates of drug metabolism among individuals. PMID- 26681737 TI - T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes. AB - OBJECTIVE: Patient-specific (unique) tumour antigens, encoded by somatically mutated cancer genes, generate neoepitopes that are implicated in the induction of tumour-controlling T cell responses. Recent advancements in massive DNA sequencing combined with robust T cell epitope predictions have allowed their systematic identification in several malignancies. DESIGN: We undertook the identification of unique neoepitopes in colorectal cancers (CRCs) by using high throughput sequencing of cDNAs expressed by standard cancer cell cultures, and by related cancer stem/initiating cells (CSCs) cultures, coupled with a reverse immunology approach not requiring human leukocyte antigen (HLA) allele-specific epitope predictions. RESULTS: Several unique mutated antigens of CRC, shared by standard cancer and related CSC cultures, were identified by this strategy. CD8+ and CD4+ T cells, either autologous to the patient or derived from HLA-matched healthy donors, were readily expanded in vitro by peptides spanning different cancer mutations and specifically recognised differentiated cancer cells and CSC cultures, expressing the mutations. Neoepitope-specific CD8+ T cell frequency was also increased in a patient, compared with healthy donors, supporting the occurrence of clonal expansion in vivo. CONCLUSIONS: These results provide a proof-of-concept approach for the identification of unique neoepitopes that are immunogenic in patients with CRC and can also target T cells against the most aggressive CSC component. PMID- 26681740 TI - PI3K Inhibitor Improves PFS in BELLE-2 Trial. AB - Adding a PI3K inhibitor to anti-estrogen receptor therapy may be a viable treatment option for women with advanced hormone receptor-positive breast cancer that becomes resistant to endocrine therapy, according to findings from the phase III BELLE-2 trial, presented at the 2015 San Antonio Breast Cancer Symposium. PMID- 26681745 TI - The Effect of Danazol in Primary Immune Thrombocytopenia: An Analysis of a Large Cohort From a Single Center in China. AB - AIM: This study assessed the long-term benefits and side effects of low-to-medium dose of danazol therapy in primary immune thrombocytopenia (ITP). METHODS: The retrospective analysis included 319 patients with ITP who accepted danazol therapy. Patients accepted danazol alone or in combination with glucocorticoids. Clinical outcome and tolerance were assessed in all patients. RESULTS: Among patients with persistent or chronic ITP, the overall response rate of danazol therapy was 65.0%. Sixty-five (63.1%) of the 103 patients reached remission with danazol alone, and 93 (48.7%) of the 191 patients who accepted combination therapies acquired remission and discontinued glucocorticoids successfully. Age and previous treatments were 2 risk factors for response rate. In newly diagnosed patients with ITP, the response rate and median response time did not differ significantly with or without danazol. However, the relapse rate was significantly lower in patients administered danazol combined with glucocorticoids than those accepted glucocorticoids alone. Totally, 21.1% of the patients experienced mild or moderate side effects, and 1.2% of the patients discontinued treatment due to intolerable side effects. CONCLUSION: Low-to-medium dosage of danazol is better tolerated and effective in patients with ITP, even in those refractory to other treatments. Combination of danazol and glucocorticoids for initial treatment may decrease relapse rates to achieve well-tolerated long term remission. PMID- 26681746 TI - Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations. AB - Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD). The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish. The gnotobiotic stickleback model that we have developed therefore provides a platform for future studies mapping the natural genetic basis of the variation in immune response to microbes. PMID- 26681748 TI - Pro: Should phosphate binders be used in chronic kidney disease stage 3-4? AB - Convincing epidemiological data have repeatedly shown that increased phosphate levels as well as generous phosphate intakes are associated with unfavourable outcome both in normal and chronically impaired kidney disease (CKD) individuals. Indeed, evidence suggest that impaired phosphate metabolism is associated with markers of cardiovascular damage such as left ventricular hypertrophy, arterial stiffness or vascular calcification as well as mortality. Although current guidelines suggest phosphate control in CKD, evidence on the impact of different approaches to minimize phosphate burden on clinically meaningful outcome are still lacking. How to manipulate, when to start in the course of CKD and to what extent to control phosphate metabolism still remain to be addressed by properly designed clinical studies. Treatment decisions should be based on a risk-benefit assessment to avoid unnecessary exposure to potentially harmful side effects of available compounds. The focus and the ambition of this review are to summarize current evidence and to provide a point of care suggestion on the use of phosphate binders in CKD stage 3 and 4 patients. PMID- 26681747 TI - Con: Phosphate binders in chronic kidney disease. AB - Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications. PMID- 26681749 TI - Moderator's view: Phosphate binders in chronic kidney disease patients: a clear 'No' at the moment, but stay tuned. AB - Particularly because the risk of harm cannot be safely excluded, the use of phosphate binders in chronic kidney disease (CKD) patients demands caution. Yet, the clinical inertia concerning phosphate burden is unjustified. Inorganic, phosphate esters added to preserve food represent an important component of dietary phosphate load. These compounds are easily absorbable and have a measurable effect on serum phosphate, and therefore their use should be avoided in CKD patients. The ongoing CKD Optimal management with Binders and NicotinamidE (COMBINE) study, applying chelation by phosphate binders and intestinal Na-P channel blockade by nicotinamide, will establish whether this combination may effectively reduce serum phosphate and fibroblast growth factor 23 in pre dialysis CKD patients and produce improvements in surrogate measures of cardiovascular and renal damages. On the other hand, the ANSWER study will ascertain whether phosphate reduction by sevelamer carbonate may have an antiproteinuric effect in CKD patients with residual proteinuria despite effective blockade of the renin-angiotensin system. At this stage of knowledge, the use of phosphate binders in pre-dialysis CKD patients cannot be recommended. Ongoing studies will tell us whether the application of these drugs may have beneficial health effects in CKD patients at the pre-dialysis stage. PMID- 26681750 TI - Children after adoption: Exploring their psychological needs. AB - Children adopted from care are known to be at increased risk for mental health difficulties although relatively little research has been carried out to explore this question. This study assessed the mental health and psychological development of children placed for adoption by one UK Local Authority. We compared the pattern and prevalence of difficulties to existing data including that on Looked-After Children (LAC) children. Totally, 106 families were initially approached and parent interviews and at least partial questionnaire data were gathered on 47 children, 72.3% of whom were known to have been maltreated prior to adoption. Of the 34 children with a complete data set including Development and Well-Being Assessment (DAWBA), 76.4% met full criteria for at least one neurodevelopmental or mental health diagnosis, a markedly higher rate than comparison data on LAC or community samples. Less than half of those identified with a mental health diagnosis had received any prior diagnosis, and only a minority had received appropriate services. Despite the children's difficulties, the great majority of parents reported high enjoyment of bringing up their child. PMID- 26681751 TI - Angiotensinogen Exerts Effects Independent of Angiotensin II. AB - OBJECTIVE: This study determined whether angiotensinogen (AGT) has angiotensin II independent effects using multiple genetic and pharmacological manipulations. APPROACH AND RESULTS: All study mice were in low-density lipoprotein receptor -/- background and fed a saturated fat-enriched diet. In mice with floxed alleles and a neomycin cassette in intron 2 of the AGT gene (hypoAGT mice), plasma AGT concentrations were >90% lower compared with their wild-type littermates. HypoAGT mice had lower systolic blood pressure, less atherosclerosis, and diminished body weight gain and liver steatosis. Low plasma AGT concentrations and all phenotypes were recapitulated in mice with hepatocyte-specific deficiency of AGT or pharmacological inhibition of AGT by antisense oligonucleotide administration. In contrast, inhibition of AGT cleavage by a renin inhibitor, aliskiren, failed to alter body weight gain and liver steatosis in low-density lipoprotein receptor -/ mice. In mice with established adiposity, administration of AGT antisense oligonucleotide versus aliskiren led to equivalent reductions of systolic blood pressure and atherosclerosis. AGT antisense oligonucleotide administration ceased body weight gain and further reduced body weight, whereas aliskiren did not affect body weight gain during continuous saturated fat-enriched diet feeding. Structural comparisons of AGT proteins in zebrafish, mouse, rat, and human revealed 4 highly conserved sequences within the des(angiotensin I)AGT domain. des(angiotensin I)AGT, through adeno-associated viral infection in hepatocyte specific AGT-deficient mice, increased body weight gain and liver steatosis, but did not affect atherosclerosis. CONCLUSIONS: AGT contributes to body weight gain and liver steatosis through functions of the des(angiotensin I)AGT domain, which are independent of angiotensin II production. PMID- 26681752 TI - Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects. AB - OBJECTIVE: We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels. APPROACH: In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-PIMA). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)-specific cholesterol efflux capacity. RESULTS: Atorvastatin decreased low density lipoprotein cholesterol by 39% and raised HDL-C by 11% (P=0.0001) but did not increase HDL-PIMA or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% (P<0.0001) but increased HDL-PIMA by only 14%. Triglyceride levels did not correlate with HDL-PIMA (P=0.39), in contrast to their strongly negative correlation with HDL-C (P<0.0001). Combination therapy increased macrophage cholesterol efflux capacity (16%, P<0.0001) but not ABCA1-specific efflux. ABCA1-specific cholesterol efflux capacity decreased significantly (P=0.013) in statin-treated subjects, with or without niacin therapy. CONCLUSIONS: Statin therapy increased HDL-C levels but failed to increase HDL PIMA. It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-PIMA. It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL. PMID- 26681753 TI - Carboxyl-Terminal Cleavage of Apolipoprotein A-I by Human Mast Cell Chymase Impairs Its Anti-Inflammatory Properties. AB - OBJECTIVE: Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of apoA-I. APPROACH AND RESULTS: Activation of human mast cells triggered the release of granule-associated proteases chymase, tryptase, cathepsin G, carboxypeptidase A, and granzyme B. Among them, chymase cleaved apoA-I with the greatest efficiency and generated C terminally truncated apoA-I, which failed to bind with high affinity to human coronary artery endothelial cells. In tumor necrosis factor-alpha-activated human coronary artery endothelial cells, the chymase-cleaved apoA-I was unable to suppress nuclear factor-kappaB-dependent upregulation of vascular cell adhesion molecule-1 (VCAM-1) and to block THP-1 cells from adhering to and transmigrating across the human coronary artery endothelial cells. Chymase-cleaved apoA-I also had an impaired ability to downregulate the expression of tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and interleukin-8 in lipopolysaccharide activated GM-CSF (granulocyte-macrophage colony-stimulating factor)- and M-CSF (macrophage colony-stimulating factor)-differentiated human macrophage foam cells and to inhibit reactive oxygen species formation in PMA (phorbol 12-myristate 13 acetate)-activated human neutrophils. Importantly, chymase-cleaved apoA-I showed reduced ability to inhibit lipopolysaccharide-induced inflammation in vivo in mice. Treatment with chymase blocked the ability of the apoA-I mimetic peptide L 4F, but not of the protease-resistant D-4F, to inhibit proinflammatory gene expression in activated human coronary artery endothelial cells and macrophage foam cells and to prevent reactive oxygen species formation in activated neutrophils. CONCLUSIONS: The findings identify C-terminal cleavage of apoA-I by human mast cell chymase as a novel mechanism leading to loss of its anti inflammatory functions. When targeting inflamed protease-rich atherosclerotic lesions with apoA-I, infusions of protease-resistant apoA-I might be the appropriate approach. PMID- 26681754 TI - Regression of Atherosclerosis: The Journey From the Liver to the Plaque and Back. AB - Cardinal events in atherogenesis are the retention of apolipoprotein B-containing lipoproteins in the arterial wall and the reaction of macrophages to these particles. My laboratory has been interested in both the cell biological events producing apolipoprotein B-containing lipoproteins, as well as in the reversal of the damage they cause in the plaques formed in the arterial wall. In the 2013 George Lyman Duff Memorial Lecture, as summarized in this review, I covered 3 areas of my past, present, and future interests, namely, the regulation of hepatic very low density lipoprotein production by the degradation of apolipoprotein B100, the dynamic changes in macrophages in the regression of atherosclerosis, and the application of nanoparticles to both image and treat atherosclerotic plaques. PMID- 26681755 TI - Assessment of Venous Thrombosis in Animal Models. AB - Deep vein thrombosis and common complications, including pulmonary embolism and post-thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here, we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro-computed tomography, and high-frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition. PMID- 26681757 TI - Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due To Combined Estrogen Plus Progestin Therapy. AB - OBJECTIVE: To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. APPROACH AND RESULTS: Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. CONCLUSIONS: Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. PMID- 26681758 TI - Extended-Release Niacin/Laropiprant Improves Overall Efficacy of Postprandial Reverse Cholesterol Transport. AB - OBJECTIVES: Postprandial atherogenic lipoproteins, characterizing high-risk patients, correlate positively with cardiovascular events. Although the effect of niacin on fasting lipids is well established, its impact on atheroprotective reverse cholesterol transport (RCT) pathway and on functional features of circulating lipoproteins during the postprandial state remains indeterminate. APPROACH AND RESULTS: We evaluated RCT pathway during postprandial phase in dyslipidemic patients displaying a low high-density lipoprotein (HDL) cholesterol phenotype. Ten subjects on stable statin therapy received 1 g/20 mg extended release niacin/laropiprant (ERN/LRPT) for 4 weeks followed by 2 g/40 mg ERN/LRPT for additional 8 weeks. At each experimental period, postprandial hypertriglyceridemia and major steps of RCT, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein-mediated cholesteryl ester transfer, and hepatic HDL-cholesteryl ester selective uptake were evaluated. Equally, the capacity of postprandial HDL particles isolated from patients before and after ERN/LRPT treatment to mediate RCT to feces was evaluated in vivo in human apolipoprotein B/cholesteryl ester transfer protein double transgenic mouse model. Compared with baseline, ERN/LRPT significantly reduced postprandial hypertriglyceridemia (incremental area under the curve-triglyceride: -53%; P=0.02). Postprandial increase in endogenous plasma cholesteryl ester transfer protein activity was completely abolished after ERN/LRPT treatment. Despite a slight reduction in plasma cholesterol efflux capacity from human THP-1 macrophages, evaluation of global RCT efficacy by combining both ex vivo and in vivo approaches indicate that postprandial HDL particles formed under ERN/LRPT therapy displayed a greater capacity for HDL-mediated RCT to feces. CONCLUSIONS: ERN/LRPT treatment efficiently attenuates atherogenic postprandial lipemia and stimulates HDL-mediated cholesterol return to the liver and elimination into feces during postprandial phase, thus maintaining an efficient removal of cholesterol from the body. PMID- 26681756 TI - Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease. AB - OBJECTIVE: Pepducins are membrane-tethered, cell-penetrating lipopeptides that target the cytoplasmic surface of their cognate receptor. Here, we report the first human use of a protease-activated receptor-1-based pepducin, which is intended as an antiplatelet agent to prevent ischemic complications of percutaneous coronary interventions. APPROACH AND RESULTS: PZ-128 was administered by 1 to 2 hours continuous intravenous infusion (0.01-2 mg/kg) to 31 subjects with coronary artery disease or multiple coronary artery disease risk factors. Safety, antiplatelet efficacy, and pharmacokinetics were assessed at baseline and 0.5, 1, 2, 6, 24 hours, and 7 to 10 days postdosing. The inhibitory effects of PZ-128 on platelet aggregation stimulated by the protease-activated receptor-1 agonist SFLLRN (8 MUmol/L) at 30 minutes to 6 hours were dose dependent with 20% to 40% inhibition at 0.3 mg/kg, 40% to 60% at 0.5 mg/kg, and >= 80% to 100% at 1 to 2 mg/kg. The subgroup receiving aspirin in the 0.5 and 1 mg/kg dose cohorts had 65% to 100% inhibition of final aggregation to SFLLRN at 30 minutes to 2 hours and 95% to 100% inhibition by 6 hours. The inhibitory effects of 0.5 mg/kg PZ-128 were reversible with 50% recovery of aggregation to SFLLRN by 24 hours. There were no significant effects of PZ-128 on aggregation induced by AYPGKF, ADP, or collagen, indicating that the observed effects were specific to protease-activated receptor-1. The plasma half-life was 1.3 to 1.8 hours, and PZ-128 was nondetectable in urine. There were no effects on bleeding, coagulation, clinical chemistry, or ECG parameters. CONCLUSIONS: PZ-128 is a promising antiplatelet agent that provides rapid, specific, dose dependent, and reversible inhibition of platelet protease-activated receptor-1 through a novel intracellular mechanism. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01806077. PMID- 26681759 TI - Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia. AB - Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T cell leukemia virus type 1. Because of its immunosuppressive property and resistance to treatment, patients with ATL have poor prognoses. ATL cells possess the regulatory T cell (Treg) phenotype, such as CD4 and CD25, and usually express forkhead box P3 (FOXP3). However, the mechanisms of FOXP3 expression and its association with Treg-like characteristics in ATL remain unclear. Selective demethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 gene leads to stable FOXP3 expression and defines natural Tregs. Here, we focus on the functional and clinical relationship between the epigenetic pattern of the TSDR and ATL. Analysis of DNA methylation in specimens from 26 patients with ATL showed that 15 patients (58%) hypomethylated the TSDR. The FOXP3(+) cells were mainly observed in the TSDR-hypomethylated cases. The TSDR-hypomethylated ATL cells exerted more suppressive function than the TSDR-methylated ATL cells. Thus, the epigenetic analysis of the FOXP3 gene identified a distinct subtype with Treg properties in heterogeneous ATL. Furthermore, we observed that the hypomethylation of TSDR was associated with poor outcomes in ATL. These results suggest that the DNA methylation status of the TSDR is an important hallmark to define this heterogeneous disease and to predict ATL patient prognosis. PMID- 26681760 TI - Survival in multiple myeloma patients who develop second malignancies: a population-based cohort study. PMID- 26681761 TI - NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors. PMID- 26681762 TI - Clinical and molecular genetic characterization of wild-type MLL infant acute lymphoblastic leukemia identifies few recurrent abnormalities. PMID- 26681763 TI - Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice. AB - BACKGROUND AND AIMS: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through alpha4beta7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. METHODS: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. RESULTS: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. CONCLUSIONS: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. PMID- 26681764 TI - Results of the Fifth Scientific Workshop of the ECCO (II): Pathophysiology of Perianal Fistulizing Disease. AB - The fifth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn's disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-to mesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work. PMID- 26681765 TI - Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. AB - BACKGROUND: The proteasome plays a vital role in the physiology of glioblastoma (GBM), and proteasome inhibition can be used as a strategy for treating GBM. Marizomib is a second-generation, irreversible proteasome inhibitor with a more lipophilic structure that suggests the potential for penetrating the blood-brain barrier. While bortezomib and carfilzomib, the 2 proteasome inhibitors approved for treatment of multiple myeloma, have little activity against malignant gliomas in vivo, marizomib could be a novel therapeutic strategy for primary brain tumors. METHODS: The in-vitro antitumor activity of marizomib was studied in glioma cell lines U-251 and D-54. The ability of marizomib to cross the blood brain barrier and regulate proteasome activities was evaluated in cynomolgus monkeys and rats. The antitumor effect of marizomib in vivo was tested in an orthotopic xenograft model of human GBM. RESULTS: Marizomib inhibited the proteasome activity, proliferation, and invasion of glioma cells. Meanwhile, free radical production and apoptosis induced by marizomib could be blocked by antioxidant N-acetyl cysteine. In animal studies, marizomib distributed into the brain at 30% of blood levels in rats and significantly inhibited (>30%) baseline chymotrypsin-like proteasome activity in brain tissue of monkeys. Encouragingly, the immunocompromised mice, intracranially implanted with glioma xenografts, survived significantly longer than the control animals (P < .05) when treated with marizomib. CONCLUSIONS: These preclinical studies demonstrated that marizomib can cross the blood-brain barrier and inhibit proteasome activity in rodent and nonhuman primate brain and elicit a significant antitumor effect in a rodent intracranial model of malignant glioma. PMID- 26681766 TI - Targeted next-generation sequencing panel (GlioSeq) provides comprehensive genetic profiling of central nervous system tumors. AB - BACKGROUND: Identification of genetic changes in CNS tumors is important for the appropriate clinical management of patients. Our objective was to develop a next generation sequencing (NGS) assay for simultaneously detecting the various types of genetic alterations characteristic for adult and pediatric CNS tumors that can be applied to small brain biopsies. METHODS: We report an amplification-based targeted NGS assay (GlioSeq) that analyzes 30 genes for single nucleotide variants (SNVs) and indels, 24 genes for copy number variations (CNVs), and 14 types of structural alterations in BRAF, EGFR, and FGFR3 genes in a single workflow. GlioSeq performance was evaluated in 54 adult and pediatric CNS tumors, and the results were compared with fluorescence in-situ hybridization, Sanger sequencing, and reverse transcription PCR. RESULTS: GlioSeq correctly identified 71/71 (100%) genetic alterations known to be present by conventional techniques, including 56 SNVs/indels, 9 CNVs, 3 EGFRvIII, and 3 KIAA1549-BRAF fusions. Only 20 ng of DNA and 10 ng of RNA were required for successful sequencing of 100% frozen and 96% formalin-fixed, paraffin-embedded tissue specimens. The assay sensitivity was 3%-5% of mutant alleles for SNVs and 1%-5% for gene fusions. The most commonly detected alterations were IDH1, TP53, TERT, ATRX. CDKN2A, and PTEN in high-grade gliomas, followed by BRAF fusions in low-grade gliomas and H3F3A mutations in pediatric gliomas. CONCLUSIONS: GlioSeq NGS assay offers accurate and sensitive detection of a wide range of genetic alterations in a single workflow. It allows rapid and cost-effective profiling of brain tumor specimens and thus provides valuable information for patient management. PMID- 26681769 TI - A generalized resistance resource: faith. A nursing view. AB - Based on Aaron Antonovsky's salutogenic model, the authors of this article aim to analyze the term Faith as a Generalized Resistance Resource (GRR) of people's health and to delve the relevance of this construct to clinical practice in Nursing. The authors consider that, in order for nurses to intervene in the promotion of faith so as to bring health benefits to people, a solid educational training in this subject area is required by nursing students. PMID- 26681767 TI - Isorhapontigenin suppresses growth of patient-derived glioblastoma spheres through regulating miR-145/SOX2/cyclin D1 axis. AB - BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor, and glioma stem cells (GSCs) are considered a major source of treatment resistance for glioblastoma. Identifying new compounds that inhibit the growth of GSCs and understanding their underlying molecular mechanisms are therefore important for developing novel therapy for GBM. METHODS: We investigated the potential inhibitory effect of isorhapontigenin (ISO), an anticancer compound identified in our recent investigations, on anchorage-independent growth of patient-derived glioblastoma spheres (PDGS) and its mechanism of action. RESULTS: ISO treatment resulted in significant anchorage-independent growth inhibition, accompanied with cell cycle G0-G1 arrest and cyclin D1 protein downregulation in PDGS. Further studies established that cyclin D1 was downregulated by ISO at transcription levels in a SOX2-dependent manner. In addition, ISO attenuated SOX2 expression by specific induction of miR-145, which in turn suppressed 3'UTR activity of SOX2 mRNA without affecting its mRNA stability. Moreover, ectopic expression of exogenous SOX2 rendered D456 cells resistant to induction of cell cycle G0-G1 arrest and anchorage-independent growth inhibition upon ISO treatment, whereas inhibition of miR-145 resulted in D456 cells resistant to ISO inhibition of SOX2 and cyclin D1 expression. In addition, overexpression of miR-145 mimicked ISO treatment in D456 cells. CONCLUSIONS: ISO induces miR-145 expression, which binds to the SOX2 mRNA 3'UTR region and inhibits SOX2 protein translation. Inhibition of SOX2 leads to cyclin D1 downregulation and PDGS anchorage-independent growth inhibition. The elucidation of the miR-145/SOX2/cyclin D1 axis in PDGS provides a significant insight into understanding the anti-GBM effect of ISO compound. PMID- 26681770 TI - Electronic health literacy of older Hispanics with diabetes. AB - Although the internet increases the availability of diabetes-related health information, health care consumers need to have different skills in order to obtain, interpret and evaluate such information. The eHealth literacy scale (eHEALS) was originally developed to assess consumers' perceived skills at using information technology for health. The objective of this study was to explore the experiences of older Hispanics' with type 2 diabetes in using the internet for diabetes management. This study was conducted in the USA among a convenience sample of older Hispanics with type 2 diabetes (n = 20) who attended a senior center in East Harlem, New York City. All participants first completed eHEALS and a demographic, diabetes-related, and smart phone use form either in English or Spanish and then participated in a focus group. Descriptive statistics and a univariate exploratory analysis were conducted to determine differences in electronic health literacy based on age or gender. In addition, qualitative data from the focus groups were analyzed. No significant differences were found based on age (F = 0.76, p = 0.66), but a t-test found significant differences based on gender (t = -2.67, df = 18, p = 0.015). During the qualitative data analysis, five themes were identified from the focus group responses. Although the participants had access to the internet, they were not using the technology to access diabetes-related health information. Given the small sample size in this study, the Spanish version of the instrument needs to be used in a larger sample and further psychometric testing. PMID- 26681768 TI - Gelatinase activity imaged by activatable cell-penetrating peptides in cell-based and in vivo models of stroke. AB - Matrix metalloproteinases (MMPs), particularly gelatinases (MMP-2/-9), are involved in neurovascular impairment after stroke. Detection of gelatinase activity in vivo can provide insight into blood-brain barrier disruption, hemorrhage, and nerve cell injury or death. We applied gelatinase-activatable cell-penetrating peptides (ACPP) with a cleavable l-amino acid linker to examine gelatinase activity in primary neurons in culture and ischemic mouse brain in vivo We found uptake of Cy5-conjugated ACPP (ACPP-Cy5) due to gelatinase activation both in cultured neurons exposed to n-methyl-d-aspartate and in mice after cerebral ischemia. Fluorescence intensity was significantly reduced when cells or mice were treated with MMP inhibitors or when a cleavage-resistant ACPP Cy5 was substituted. We also applied an ACPP dendrimer (ACPPD) conjugated with multiple Cy5 and/or gadolinium moieties for fluorescence and magnetic resonance imaging (MRI) in intact animals. Fluorescence analysis showed that ACPPD was detected in sub-femtomole range in ischemic tissues. Moreover, MRI and inductively coupled plasma mass spectrometry revealed that ACPPD produced quantitative measures of gelatinase activity in the ischemic region. The resulting spatial pattern of gelatinase activity and neurodegeneration were very similar. We conclude that ACPPs are capable of tracing spatiotemporal gelatinase activity in vivo, and will therefore be useful in elucidating mechanisms of gelatinase-mediated neurodegeneration after stroke. PMID- 26681771 TI - Heterogeneous impact of classic atherosclerotic risk factors on different arterial territories: the EPIC-Norfolk prospective population study. AB - AIMS: Particular atherosclerotic risk factors may differ in their association with atherosclerosis across vascular territories. Few studies have compared the associations between multiple risk factors and cardiovascular disease (CVD) manifestations in one population. We studied the strength of the associations between traditional risk factors including coronary artery disease (CAD), ischaemic and haemorrhagic stroke, abdominal aortic aneurysms (AAAs), and peripheral arterial disease (PAD). METHODS AND RESULTS: This analysis included 21 798 participants of the EPIC-Norfolk population study, without previous CVD. Events were defined as hospitalization or mortality, coded using ICD-10. The associations between the risk factors, such as low-density lipoprotein cholesterol, systolic blood pressure (SBP), and smoking, and the various CVD manifestations were compared using competing risk analyses. During 12.1 years, 3087 CVD events were recorded. The associations significantly differed across CVD manifestations. Low-density lipoprotein cholesterol was strongly associated with CAD [adjusted hazard rate (aHR) highest vs. lowest quartile 1.63, 95% CI 1.44 1.86]. Systolic blood pressure was a strong risk factor for PAD (aHR highest vs. lowest quartile 2.95, 95% CI 1.78-4.89) and ischaemic stroke (aHR highest vs. lowest quartile 2.48, 95% CI 1.55-3.97), but not for AAA. Smoking was strongly associated with incident AAA (aHR current vs. never 7.66, 95% CI 4.50-13.04) and PAD (aHR current vs. never 4.66, 95% CI 3.29-6.61), but not with haemorrhagic stroke. CONCLUSION: The heterogeneity in the risk factor-CVD associations supports the concept of pathophysiological differences between atherosclerotic CVD manifestations and could have implications for CVD prevention. PMID- 26681772 TI - Effects of Smart-Tablet-Based Neurofeedback Training on Cognitive Function in Children with Attention Problems. AB - We sought to determine whether smart-tablet-based neurofeedback could improve executive function-including attention, working memory, and self-regulation-in children with attention problems. Forty children (10-12 years old) with attention problems, as determined by ratings on the Conners Parent Rating Scale, were assigned to either a neurofeedback group that received 16 sessions or a control group. A comprehensive test battery that assessed general intelligence, visual and auditory attention, attentional shifting, response inhibition and behavior rating scales were administered to both groups before neurofeedback training. Several neuropsychological tests were conducted at posttraining and follow-up assessment. Scores on several neuropsychological tests and parent behavior rating scales showed significant improvement in the training group but not in the controls. The improvements remained through the follow-up assessment. This study suggests that the smart-tablet-based neurofeedback training program might improve cognitive function in children with attention problems. PMID- 26681773 TI - Sequential treatment with 5-aza-2'-deoxycytidine and deacetylase inhibitors reactivates HIV-1. AB - Reactivation of HIV gene expression in latently infected cells together with an efficient cART has been proposed as an adjuvant therapy aimed at eliminating/decreasing the reservoir size. Results from HIV clinical trials using deacetylase inhibitors (HDACIs) question the efficiency of these latency reversing agents (LRAs) used alone and underline the need to evaluate other LRAs in combination with HDACIs. Here, we evaluated the therapeutic potential of a demethylating agent (5-AzadC) in combination with clinically tolerable HDACIs in reactivating HIV-1 from latency first in vitro and next ex vivo. We showed that a sequential treatment with 5-AzadC and HDACIs was more effective than the corresponding simultaneous treatment both in vitro and ex vivo. Interestingly, only two of the sequential LRA combinatory treatments tested induced HIV-1 particle recovery in a higher manner than the drugs alone ex vivo and at concentrations lower than the human tolerable plasmatic concentrations. Taken together, our data reveal the benefit of using combinations of 5-AzadC with an HDACI and, for the first time, the importance of treatment time schedule for LRA combinations in order to reactivate HIV. PMID- 26681774 TI - Investigating the Effects of Exposure to Waterpipe Smoke on Pregnancy Outcomes Using an Animal Model. AB - INTRODUCTION: In recent years, waterpipe tobacco smoking has been increasing in popularity all over the world. In this study, we explored effects of waterpipe smoking on pregnancy outcomes in rats. METHODS: Animals were exposed to waterpipe tobacco smoking using a whole body exposure system 2 hours per day during pregnancy. A control group was exposed to fresh air only. RESULTS: The results showed significant association between exposure to waterpipe smoke during pregnancy and low birth weight (P < .01) and neonatal death (P < .01). In addition, the rate of growth of offspring of the waterpipe group was significantly lower than that of control group as measured by body weight gain during the first 3 months of life (P < .001). No effect was found for waterpipe smoking on mean number of progeny and male to female ratio among offspring. CONCLUSION: Waterpipe smoking is associated with adverse effects on pregnancy outcomes. IMPLICATIONS: In this study, we investigated for the first time the effect of waterpipe smoking on pregnancy outcomes using animal model. The results clearly showed that waterpipe smoking is associated with adverse effects on pregnancy outcomes that include low birth weigh, neonatal survival, and growth retardation. PMID- 26681775 TI - "My First Thought was Croutons": Perceptions of Cigarettes and Cigarette Smoke Constituents Among Adult Smokers and Nonsmokers. AB - INTRODUCTION: Understanding what people think about harmful and potentially harmful constituents in cigarettes and cigarette smoke has new urgency given legislation requiring US Food and Drug Administration (FDA) to disclose constituent information. Our study sought to obtain qualitative information on what people think about these constituents and the language they use to talk about them. METHODS: We conducted six focus groups in 2014 with 40 adults in North Carolina. Open-ended questions focused on cigarette and cigarette smoke constituents in general and on the 18 constituents on the FDA's abbreviated list. We coded the transcripts for emergent themes, and all four coders discussed themes until we reached consensus. RESULTS: Participants knew that cigarette smoke contains chemicals but did not know how many chemicals nor what those chemicals are, beyond tar and nicotine. Dangers of constituents mentioned included "chemicals," physical disease, and addiction. Participants incorrectly believed harmful constituents came primarily from tobacco companies' additives. For unfamiliar constituents, people tried to make associations based on similar sounding words. Recognizable constituents that participants associated with health harms most discouraged them from wanting to smoke. Most participants wanted to know health harms associated with constituents and what else the chemicals were in. CONCLUSIONS: Participants showed enthusiasm for learning more information about constituents, and also showed substantial misunderstandings about the source of harmful constituents. Our findings contribute to the limited body of research on adults' knowledge and perceptions of cigarette smoke constituents and can aid the FDA as it plans to disclose constituent information to the public. IMPLICATIONS: Our study provides information about adults' understanding of cigarette smoke constituents and what adults would like to know about these constituents. This information can help communication campaigns describe cigarette smoke constituents in a way that discourages people from wanting to smoke. PMID- 26681776 TI - CipA of Acinetobacter baumannii Is a Novel Plasminogen Binding and Complement Inhibitory Protein. AB - Acinetobacter baumannii is an emerging opportunistic pathogen, responsible for up to 10% of gram-negative, nosocomial infections. The global increase of multidrug resistant and pan-resistant Acinetobacter isolates presents clinicians with formidable challenges. To establish a persistent infection,A. baumannii must overcome the detrimental effects of complement as the first line of defense against invading microorganisms. However, the immune evasion principles underlying serum resistance inA. baumannii remain elusive. Here, we identified a novel plasminogen-binding protein, termed CipA. Bound plasminogen, upon conversion to active plasmin, degraded fibrinogen and complement C3b and contributed to serum resistance. Furthermore, CipA directly inhibited the alternative pathway of complement in vitro, irrespective of its ability to bind plasminogen. A CipA-deficient mutant was efficiently killed by human serum and showed a defect in the penetration of endothelial monolayers, demonstrating that CipA is a novel multifunctional protein that contributes to the pathogenesis ofA. baumannii. PMID- 26681779 TI - Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way? PMID- 26681778 TI - Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection. AB - BACKGROUND: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. METHODS: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. RESULTS: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. CONCLUSIONS: Currently available standard PrEP is a cost saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives. PMID- 26681777 TI - Numerical Distributions of Parasite Densities During Asymptomatic Malaria. AB - BACKGROUND: Asymptomatic parasitemia is common even in areas of low seasonal malaria transmission, but the true proportion of the population infected has not been estimated previously because of the limited sensitivity of available detection methods. METHODS: Cross-sectional malaria surveys were conducted in areas of low seasonal transmission along the border between eastern Myanmar and northwestern Thailand and in western Cambodia. DNA was quantitated by an ultrasensitive polymerase chain reaction (uPCR) assay (limit of accurate detection, 22 parasites/mL) to characterize parasite density distributions for Plasmodium falciparum and Plasmodium vivax, and the proportions of undetected infections were imputed. RESULTS: The prevalence of asymptomatic malaria as determined by uPCR was 27.5% (1303 of 4740 people tested). Both P. vivax and P. falciparum density distributions were unimodal and log normal, with modal values well within the quantifiable range. The estimated proportions of all parasitemic individuals identified by uPCR were >70% among individuals infected with P. falciparum and >85% among those infected with P. vivax. Overall, 83% of infections were predicted to be P. vivax infections, 13% were predicted to be P. falciparum infections, and 4% were predicted to be mixed infections. Geometric mean parasite densities were similar; 5601 P. vivax parasites/mL and 5158 P. falciparum parasites/mL. CONCLUSIONS: This uPCR method identified most infected individuals in malaria-endemic areas. Malaria parasitemia persists in humans at levels that optimize the probability of generating transmissible gametocyte densities without causing illness. PMID- 26681780 TI - Characterization of a novel 8R,11S-linoleate diol synthase from Penicillium chrysogenum by identification of its enzymatic products. AB - To identify novel fatty acid diol synthases, putative candidate sequences from Penicillium species were analyzed, and hydroxy fatty acid production by crude Penicillium enzyme extracts was assessed. Penicillium chrysogenum was found to produce an unknown dihydroxy fatty acid, a candidate gene implicated in this production was cloned and expressed, and the expressed enzyme was purified. The product obtained by the reaction of the purified enzyme with linoleic acid was identified as 8R,11S-dihydroxy-9,12(Z,Z)-octadecadienoic acid (8R,11S-DiHODE). The catalytic efficiency of this enzyme toward linoleic acid was the highest among the unsaturated fatty acids tested, indicating that this enzyme was a novel 8R,11S-linoleate diol synthase (8R,11S-LDS). A sexual stage in the life cycle of P. chrysogenum has recently been discovered, and 8R,11S-DiHODE produced by 8R,11S LDS may constitute a precocious sexual inducer factor, responsible for regulating the sexual and asexual cycles of this fungus. PMID- 26681781 TI - Fatal Myocarditis Associated With HHV-6 Following Immunosuppression in Two Children. AB - Fatal myocarditis is a rare complication in immunosuppressed children. Recent reports have linked human herpesvirus 6 (HHV-6) infection, typically a benign infection in childhood, with myocarditis. HHV-6 can reactivate during periods of immunosuppression. Here, we report 2 cases in which children were immunosuppressed, one for treatment of Evans syndrome and the other post hematopoietic stem cell transplantation, who developed rapid and fatal HHV-6 associated myocarditis. These cases suggest that HHV-6 infection should be considered as an etiology of myocarditis in immunosuppressed patients regardless of correlating blood levels. Early treatment of HHV-6 in patients with myocarditis could improve morbidity and mortality. PMID- 26681782 TI - Use of a Checklist and Clinical Decision Support Tool Reduces Laboratory Use and Improves Cost. AB - OBJECTIVE: We hypothesized that a daily rounding checklist and a computerized order entry (CPOE) rule that limited the scheduling of complete blood cell counts and chemistry and coagulation panels to a 24-hour interval would reduce laboratory utilization and associated costs. METHODS: We performed a retrospective analysis of these initiatives in a pediatric cardiovascular ICU (CVICU) that included all patients with congenital or acquired heart disease admitted to the cardiovascular ICU from September 1, 2008, until April 1, 2011. Our primary outcomes were the number of laboratory orders and cost of laboratory orders. Our secondary outcomes were mortality and CVICU and hospital length of stay. RESULTS: We found a reduction in laboratory utilization frequency in the checklist intervention period and additional reduction in the CPOE intervention period [complete blood count: 31% and 44% (P < .0001); comprehensive chemistry panel: 48% and 72% (P < .0001); coagulation panel: 26% and 55% (P < .0001); point of care blood gas: 43% and 44% (P < .0001)] compared with the preintervention period. Projected yearly cost reduction was $717,538.8. There was no change in adjusted mortality rate (odds ratio 1.1, 95% confidence interval 0.7-1.9, P = .65). CVICU and total length of stay (days) was similar in the pre- and postintervention periods. CONCLUSIONS: Use of a daily checklist and CPOE rule reduced laboratory resource utilization and cost without adversely affecting adjusted mortality or length of stay. CPOE has the potential to hardwire resource management interventions to augment and sustain the daily checklist. PMID- 26681783 TI - Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis. AB - BACKGROUND: The clinical presentation of pediatric inflammatory bowel disease (IBD) is often nonspecific and overlaps with functional gastrointestinal disorders. OBJECTIVE: To determine the diagnostic accuracy of symptoms, signs, noninvasive tests, and test combinations that can assist the clinician with the diagnosis of IBD in symptomatic children. METHODS: A literature search was conducted of Medline and Embase. Two reviewers independently selected studies reporting on the diagnostic accuracy of tests for IBD, with confirmation by endoscopy and histopathology or clinical follow-up, in children with chronic gastrointestinal symptoms. Two reviewers independently extracted data and assessed study quality with the QUADAS-2, an evidence-based quality assessment tool for diagnostic accuracy studies. RESULTS: Nineteen studies were included (N = 2806). Symptoms (abdominal pain, diarrhea, rectal bleeding, and weight loss) had pooled sensitivities ranging from 0.48 to 0.82 and specificities ranging from 0.17 to 0.78. Of all the blood markers, C-reactive protein (CRP) (9 studies) and albumin (6 studies) had the best performance, with pooled sensitivities of 0.63 (0.51-0.73) and 0.48 (0.31-0.66), respectively, and specificities of 0.88 (0.80 0.93) and 0.94 (0.86-0.98). Assessment of fecal calprotectin (FCal) (10 studies) had a pooled sensitivity of 0.99 (0.92-1.00) and a specificity of 0.65 (0.54 0.74). One limitation was that none of the studies was conducted in nonreferred children. CONCLUSIONS: In children whose pediatrician is considering an endoscopy, symptoms are not accurate enough to identify low-risk patients in whom an endoscopy can be avoided. FCal, CRP, and albumin findings are potentially of clinical value, given their ability to select children at low risk (negative FCal test result) or high risk (positive CRP or albumin test result) for IBD. PMID- 26681784 TI - Inclusive Branding Strategies for Domestic Violence Agencies: Embracing Opportunities to Reach and Better Serve Male-Identified Survivors. AB - Successful strategies for branding that are inclusive of male-identified survivors were identified in this qualitative study through semi-structured interviews with leaders from six domestic violence agencies across the United States: four represented traditional domestic violence agencies and two represented specialized agencies with expertise in providing services to nontraditional survivors. The strategic implementation of (a) inclusive language, (b) visual diversity, (c) community outreach, and (d) communication channels emerged as successful strategies in branding in an inclusive way for male identified survivors. The implementation of these successful strategies provides the opportunity for domestic violence agencies to create an inclusive environment for male-identified survivors and would contribute to a paradigm shift in how domestic violence is viewed. PMID- 26681785 TI - "Correcting an Erring Wife Is Normal": Moral Discourses of Spousal Violence in Ghana. AB - This study draws insights from discursive psychology to explore moral discourses of spousal violence in Ghana. In particular, it investigates how sociocultural norms and practices are invoked in talk of perpetrators and victims as moral warrants for husband-to-wife abuse in Ghana. Semi-structured focus group and personal interviews were conducted with a total of 40 participants: 16 victims, 16 perpetrators, and eight key informants from rural and urban Ghana. Participants' discursive accounts suggest that husbands have implicit moral right and obligation to punish their wives for disobedience and other infractions against male authority in marriage. Both perpetrators and victims build their talk around familiar normative discourses and practices that provide tacit support for spousal violence in Ghana. While perpetrators mobilize culturally resonant and normative repertoires to justify abuse, blame their victims, and manage their moral accountability; victims position husband-to-wife abuse as normal, legitimate, disciplinary, and corrective. These moral discourses of spousal violence apparently serve to relieve perpetrators of moral agency; prime battered women to accept abuse; and devastate their agency to leave abusive marital relationships. The findings contribute to our understanding of how cultural and social norms of spousal violence are morally constituted, reproduced, and sustained in talk of perpetrators, victims, and other key members of society. PMID- 26681786 TI - Screening for Partner Violence Among Family Mediation Clients: Differentiating Types of Abuse. AB - Family mediation is mandated in Australia for couples in dispute over separation and parenting as a first step in dispute resolution, except where there is a history of intimate partner violence. However, validation of effective well differentiated partner violence screening instruments suitable for mediation settings is at an early phase of development. This study contributes to calls for better violence screening instruments in the mediation context to detect a differentiated range of abusive behaviors by examining the reliability and validity of both established scales, and newly developed scales that measured intimate partner violence by partner and by self. The study also aimed to examine relationships between types of abuse, and between gender and types of abuse. A third aim was to examine associations between types of abuse and other relationship indicators such as acrimony and parenting alliance. The data reported here are part of a larger mixed method, naturalistic longitudinal study of clients attending nine family mediation centers in Victoria, Australia. The current analyses on baseline cross-sectional screening data confirmed the reliability of three subscales of the Conflict Tactics Scale (CTS2), and the reliability and validity of three new scales measuring intimidation, controlling and jealous behavior, and financial control. Most clients disclosed a history of at least one type of violence by partner: 95% reported psychological aggression, 72% controlling and jealous behavior, 50% financial control, and 35% physical assault. Higher rates of abuse perpetration were reported by partner versus by self, and gender differences were identified. There were strong associations between certain patterns of psychologically abusive behavior and both acrimony and parenting alliance. The implications for family mediation services and future research are discussed. PMID- 26681787 TI - Self-Compassion and Responses to Trauma: The Role of Emotion Regulation. AB - Emerging literature suggests that self-compassion may be an important concept for understanding recovery from the impact of trauma and posttraumatic stress disorder (PTSD). The present study explored the interconnection among self compassion, resilience, emotion dysregulation, and PTSD symptom severity in a sample of treatment-seeking women with PTSD. We predicted that self-compassion would be negatively related to PTSD symptom severity and to emotion dysregulation, and positively related to resilience. The results supported our main hypotheses. In addition, emotion dysregulation mediated the relationship between PTSD symptom severity and self-compassion and affected the relationship between self-compassion and resilience. These findings corroborate previous research that points to the important role of self-compassion in mental health and in the aftermath of stressful life events. The present study expands this research by demonstrating that PTSD symptom severity is negatively related to self-compassion in a clinical population of women with experiences of severe and repeated interpersonal trauma. PMID- 26681788 TI - Exposure to Genocide as a Risk Factor for Homicide Perpetration in Rwanda: A Population-Based Case-Control Study. AB - A population-based case-control study was conducted to assess the relationship between genocide exposure and homicide perpetration in Rwanda. A sample of 150 homicide perpetrators who were charged with and confessed to having committed homicide between 1 May 2011 and 31 May 2013 and 450 controls were enrolled. Cases were matched to controls by neighborhood, age and sex. Socio-demographic, background and genocide-related information was collected from study subjects' next of kin. Four characteristics of genocide exposure were: genocide survivor, genocide perpetrator, having lost a first-degree relative to genocide and having a first-degree relative convicted of genocide. We assessed the impact of each genocide-exposure variable using conditional logistic regression. Of the 150 cases, 124 (82.7%) were male and 26 (17.3%) were female. The mean age of the alleged homicide perpetrators was 33 years, with a peak in the age group 20-29 years (39.3%). After adjusting for socio-demographic characteristics and past common criminal records, having a first-degree relative who had been convicted of genocide crimes was a significant predictor for homicide perpetration (odds ratio [OR] = 14.4, 95% confidence interval [CI] = 1.6-129.4). Being a genocide perpetrator, a genocide survivor and having lost a first-degree family member to genocide were not identified as risk factors for homicide perpetration. In Rwanda, young people who experienced early exposure to trauma by witnessing their first-degree relatives' active participation in the genocide, are more likely to commit homicide. Socio-economic and psychotherapeutic programs targeting this population group are needed to rehabilitate these young people for violent behavior change. PMID- 26681790 TI - Teratological Nymphal Ixodes scapularis (Acari: Ixodidae) From Wisconsin. AB - Abnormalities of physiological development (teratological forms) in ticks are rare. The occurrence of gigantism, dwarfism, gynandromorphs, missing legs, extra legs, and asymmetries is most often reported from lab-reared specimens, but has been observed in field-collected specimens. All morphologically anomalous ticks (besides gynandromorphy) described to date are from species other than Ixodes scapularis Say (Acari: Ixodidae). Here we describe four teratological I. scapularis nymphs collected while dragging vegetation in Wisconsin in 2015, including two asymmetrical ticks, one with a missing leg, and one with an extra leg. PMID- 26681791 TI - Letter from the Editor-in-Chief. PMID- 26681789 TI - Linkages of Weather and Climate With Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), Enzootic Transmission of Borrelia burgdorferi, and Lyme Disease in North America. AB - Lyme disease has increased both in incidence and geographic extent in the United States and Canada over the past two decades. One of the underlying causes is changes during the same time period in the distribution and abundance of the primary vectors: Ixodes scapularis Say and Ixodes pacificus Cooley and Kohls in eastern and western North America, respectively. Aside from short periods of time when they are feeding on hosts, these ticks exist in the environment where temperature and relative humidity directly affect their development, survival, and host-seeking behavior. Other important factors that strongly influence tick abundance as well as the proportion of ticks infected with the Lyme disease spirochete, Borrelia burgdorferi, include the abundance of hosts for the ticks and the capacity of tick hosts to serve as B. burgdorferi reservoirs. Here, we explore the linkages between climate variation and: 1) duration of the seasonal period and the timing of peak activity; 2) geographic tick distributions and local abundance; 3) enzootic B. burgdorferi transmission cycles; and 4) Lyme disease cases. We conclude that meteorological variables are most influential in determining host-seeking phenology and development, but, while remaining important cofactors, additional variables become critical when exploring geographic distribution and local abundance of ticks, enzootic transmission of B. burgdorferi, and Lyme disease case occurrence. Finally, we review climate change driven projections for future impact on vector ticks and Lyme disease and discuss knowledge gaps and research needs. PMID- 26681793 TI - Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice. AB - Mood disorders and chronic pain are closely linked, but limited progress has been made in understanding the role of chronic and neuropathic pain in the aetiopathogenesis of depression. To explore the pathological mechanisms that mediate the association between pain and depressive-like behaviours, we studied the time-dependent effect of neuropathic pain on the development of anxiety-like and despair behaviours in CD1 mice. We analysed behavioural data, neuroinflammation reactions and changes in neurotransmitter (glutamate and serotonin) levels in the mouse prefrontal cortex. Sciatic-operated mice displayed long-lasting anxiety-like and despair behaviours, starting 5 and 20 days after partial sciatic nerve ligation, respectively. Glutamatergic neurotransmission and IL-1beta cytokine expression were enhanced in the prefrontal cortex of mice with neuropathic pain. We found no change in serotonin metabolism, cytokine IL-6 or brain-derived neurotrophic factor levels. While sciatic-operated mice exposed to intermittent ethanol intake (20% v/v) using the drinking in the dark procedure consumed higher amounts of ethanol than sham-operated mice, thermal allodynia and despair behaviour were not attenuated by ethanol consumption. Our findings reveal an association between glutamatergic neurotransmission and pain-induced mood disorders, and indicate that moderate ethanol consumption does not relieve nociceptive and depressive behaviours associated with chronic pain in mice. PMID- 26681796 TI - Medically Inappropriate or Futile Treatment: Deliberation and Justification. AB - This paper reframes the futility debate, moving away from the question "Who decides when to end what is considered to be a medically inappropriate or futile treatment?" and toward the question "How can society make policy that will best account for the multitude of values and conflicts involved in such decision making?" It offers a pragmatist moral epistemology that provides us with (1) a clear justification of why it is important to take best standards, norms, and physician judgment seriously and (2) a clear justification of why ample opportunity must be made for patients, families, and society to challenge those standards and norms. PMID- 26681798 TI - In Visible Hands: The Matter and Making of Music Therapy. AB - This study explores the topics of matter and making in music therapy through embodied reflexive retrospection with six music therapists. The participants were asked to re-enact a hand position from their memory of a significant moment in therapy. In individual research meetings, they shared their thoughts about this moment while the researcher made a body cast of their chosen hand pose. A thematic analysis of the participant narratives, the hand casts, and existing literature was used to generate the following themes: The biographic hand, The body, space, place, and time, The plural hand, Matter of the hand, and The method in hand. The research procedure facilitated an exploration of epistemological, ontological, and phenomenological perspectives in understanding music therapy practitioner experiences. The study highlights the inseparability and multiplicity of matter, making, and narrating music therapy that transcends context or therapeutic approach. PMID- 26681797 TI - Plant Nuclei Move to Escape Ultraviolet-Induced DNA Damage and Cell Death. AB - A striking feature of plant nuclei is their light-dependent movement. In Arabidopsis (Arabidopsis thaliana) leaf mesophyll cells, the nuclei move to the side walls of cells within 1 to 3 h after blue-light reception, although the reason is unknown. Here, we show that the nuclear movement is a rapid and effective strategy to avoid ultraviolet B (UVB)-induced damages. Mesophyll nuclei were positioned on the cell bottom in the dark, but sudden exposure of these cells to UVB caused severe DNA damage and cell death. The damage was remarkably reduced in both blue-light-treated leaves and mutant leaves defective in the actin cytoskeleton. Intriguingly, in plants grown under high-light conditions, the mesophyll nuclei remained on the side walls even in the dark. These results suggest that plants have two strategies for reducing UVB exposure: rapid nuclear movement against acute exposure and nuclear anchoring against chronic exposure. PMID- 26681799 TI - Performing Theory: Playing in the Music Therapy Discourse. AB - Performative writing is an art form that seeks to enliven our discourse by including the senses as a primary source of information processing. Through performative writing, one is seduced into engaging with the aesthetic. My art is music. My craft is Music Therapy. My theme is performing theory. Listen to the sound and silence of words, phrases, punctuation, syllables, format. My muses? I thank D. Soyini Madison, Ron Pelias, Philip Glass, Elliot Eisner, and Tom Barone for inspiration, and my teachers/Indigenous Elders and knowledge keepers who embraced the long tradition of oral transmission of knowledge and the healing power of sound. Stay, stay in the presence of the aesthetic. PMID- 26681800 TI - Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, +/- Docetaxel for Larynx Preservation. AB - BACKGROUND: The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. METHODS: Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038). CONCLUSION: Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy. PMID- 26681801 TI - Meaningful Questions in "Organ Preservation" - Past, Present, and Future. PMID- 26681802 TI - Analysis of the ACTN3 heterozygous genotype suggests that alpha-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion. AB - A common null polymorphism (R577X) in ACTN3 causes alpha-actinin-3 deficiency in ~ 18% of the global population. There is no associated disease phenotype, but alpha-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of alpha-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of alpha-actinin-3 expression level by comparing the muscle phenotypes of Actn3(+/-) (HET) mice to Actn3(+/+) [wild-type (WT)] and Actn3(-/-) [knockout (KO)] littermates. We show reduction in alpha-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of alpha-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations. PMID- 26681804 TI - Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division. AB - Mitochondria are dynamic organelles that divide and fuse by remodeling an outer and inner membrane in response to developmental, physiological and stress stimuli. These events are coordinated by conserved dynamin-related GTPases. The dynamics of mitochondrial morphology require coordination with mitochondrial DNA (mtDNA) to ensure faithful genome transmission, however, this process remains poorly understood. Mitochondrial division is linked to the segregation of mtDNA but how it affects cases of mtDNA heteroplasmy, where two or more mtDNA variants/mutations co-exist in a cell, is unknown. Segregation of heteroplasmic human pathogenic mtDNA mutations is a critical factor in the onset and severity of human mitochondrial diseases. Here, we investigated the coupling of mitochondrial morphology to the transmission and segregation of mtDNA in mammals by taking advantage of two genetically modified mouse models: one with a dominant negative mutation in the dynamin-related protein 1 (Drp1 or Dnm1l) that impairs mitochondrial fission and the other, heteroplasmic mice segregating two neutral mtDNA haplotypes (BALB and NZB). We show a tissue-specific response to mtDNA segregation from a defect in mitochondrial fission. Only mtDNA segregation in the hematopoietic compartment is modulated from impaired Dnm1l function. In contrast, no effect was observed in other tissues arising from the three germ layers during development and in mtDNA transmission through the female germline. Our data suggest a robust organization of a heteroplasmic mtDNA segregating unit across mammalian cell types that can overcome impaired mitochondrial division to ensure faithful transmission of the mitochondrial genome. PMID- 26681805 TI - Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7. AB - CLN7 disease is an autosomal recessive, childhood-onset neurodegenerative lysosomal storage disorder caused by the defective lysosomal membrane protein CLN7. We have disrupted the Cln7/Mfsd8 gene in mice by targeted deletion of exon 2 generating a novel knockout (KO) mouse model for CLN7 disease, which recapitulates key features of human CLN7 disease pathology. Cln7 KO mice showed increased mortality and a neurological phenotype including hind limb clasping and myoclonus. Lysosomal dysfunction in the brain of mutant mice was shown by the storage of autofluorescent lipofuscin-like lipopigments, subunit c of mitochondrial ATP synthase and saposin D and increased expression of lysosomal cathepsins B, D and Z. By immunohistochemical co-stainings, increased cathepsin Z expression restricted to Cln7-deficient microglia and neurons was found. Ultrastructural analyses revealed large storage bodies in Purkinje cells of Cln7 KO mice containing inclusions composed of irregular, curvilinear and rectilinear profiles as well as fingerprint profiles. Generalized astrogliosis and microgliosis in the brain preceded neurodegeneration in the olfactory bulb, cerebral cortex and cerebellum in Cln7 KO mice. Increased levels of LC3-II and the presence of neuronal p62- and ubiquitin-positive protein aggregates suggested that impaired autophagy represents a major pathomechanism in the brain of Cln7 KO mice. The data suggest that loss of the putative lysosomal transporter Cln7 in the brain leads to lysosomal dysfunction, impaired constitutive autophagy and neurodegeneration late in disease. PMID- 26681795 TI - Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. AB - 1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease. PMID- 26681803 TI - Whole chromosome aneuploidy in the brain of Bub1bH/H and Ercc1-/Delta7 mice. AB - High levels of aneuploidy have been observed in disease-free tissues, including post-mitotic tissues such as the brain. Using a quantitative interphase fluorescence in situ hybridization approach, we previously reported a chromosome specific, age-related increase in aneuploidy in the mouse cerebral cortex. Increased aneuploidy has been associated with defects in DNA repair and the spindle assembly checkpoint, which in turn can lead to premature aging. Here, we quantified the frequency of aneuploidy of three autosomes in the cerebral cortex and cerebellum of adult and developing brain of Bub1b(H/H) mice, which have a faulty mitotic checkpoint, and Ercc1(-/Delta7) mice, defective in nucleotide excision repair and inter-strand cross-link repair. Surprisingly, the level of aneuploidy in the brain of these murine models of accelerated aging remains as low as in the young adult brains from control animals, i.e. <1% in the cerebral cortex and ~0.1% in the cerebellum. Therefore, based on aneuploidy, these adult mice with reduced life span and accelerated progeroid features are indistinguishable from age-matched, normal controls. Yet, during embryonic development, we found that Bub1b(H/H), but not Ercc1(-/Delta7) mice, have a significantly higher frequency of aneuploid nuclei relative to wild-type controls in the cerebral cortex, reaching a frequency as high as 40.3% for each chromosome tested. Aneuploid cells in these mutant mice are likely eliminated early in development through apoptosis and/or immune-mediated clearance mechanisms, which would explain the low levels of aneuploidy during adulthood in the cerebral cortex of Bub1b(H/H) mice. These results shed light on the mechanisms of removal of aneuploidy cells in vivo. PMID- 26681806 TI - Genome-wide DNA methylation study identifies genes associated with the cardiovascular biomarker GDF-15. AB - Growth-differentiation factor 15 (GDF-15) is expressed in low to moderate levels in most healthy tissues and increases in response to inflammation. GDF-15 is associated with cardiovascular dysfunction and over-expressed in the myocardium of patients with myocardial infarction (MI). However, little is known about the function of GDF-15 in cardiovascular disease, and the underlying regulatory network of GDF-15 is not known. To investigate a possible association between GDF 15 levels and DNA methylation, we performed a genome-wide DNA methylation study of white blood cells in a population-based study (N = 717). Significant loci where replicated in an independent cohort (N = 963). We also performed a gene ontology (GO) enrichment analysis. We identified and replicated 16 CpG-sites (false discovery rate [FDR] < 0.05), at 11 independent loci including MIR21. MIR21 encodes a microRNA (miR-21) that has previously been shown to be associated with the development of heart disease. Interestingly, GDF15 mRNA contains a binding site for miR-21. Four sites were also differentially methylated in blood from participants previously diagnosed with MI and 14 enriched GO terms (FDR < 0.05, enrichment > 2) were identified, including 'cardiac muscle cell differentiation'. This study shows that GDF-15 levels are associated with differences in DNA methylation in blood cells, and a subset of the loci are also differentially methylated in participants with MI. However, there might be interactions between GDF-15 levels and methylation in other tissues not addressed in this study. These results provide novel links between GDF-15 and cardiovascular disease. PMID- 26681807 TI - AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease. AB - The adenosine monophosphate activated kinase protein (AMPK) is an evolutionary conserved protein important for cell survival and organismal longevity through the modulation of energy homeostasis. Several studies suggested that AMPK activation may improve energy metabolism and protein clearance in the brains of patients with vascular injury or neurodegenerative disease. However, in Huntington's disease (HD), AMPK may be activated in the striatum of HD mice at a late, post-symptomatic phase of the disease, and high-dose regiments of the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide may worsen neuropathological and behavioural phenotypes. Here, we revisited the role of AMPK in HD using models that recapitulate the early features of the disease, including Caenorhabditis elegans neuron dysfunction before cell death and mouse striatal cell vulnerability. Genetic and pharmacological manipulation of aak-2/AMPKalpha shows that AMPK activation protects C. elegans neurons from the dysfunction induced by human exon-1 huntingtin (Htt) expression, in a daf-16/forkhead box O dependent manner. Similarly, AMPK activation using genetic manipulation and low dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKalpha1. Furthermore, AMPK protection is active in the mouse brain as delivery of gain-of function AMPK-gamma1 to mouse striata slows down the neurodegenerative effects of mHtt. Collectively, these data highlight the importance of considering the dynamic of HD for assessing the therapeutic potential of stress-response targets in the disease. We postulate that AMPK activation is a compensatory response and valid approach for protecting dysfunctional and vulnerable neurons in HD. PMID- 26681809 TI - Planar, Polysilazane-Derived Porous Ceramic Supports for Membrane and Catalysis Applications. AB - Porous, silicon carbonitride-based ceramic support structures for potential membrane and catalysis applications were generated from a preceramic polysilazane precursor in combination with spherical, ultrahigh-molecular weight polyethylene microparticles through a sacrificial filler approach. A screening evaluation was used for the determination of the impact of both porogen content and porogen size on pore structure, strength, and permeability characteristics of planar specimens. By optimizing both the composition as well as cross-linking parameters, maximum characteristic biaxial flexural strengths of 65 MPa and porosities of 42% were achieved. The evolution of an interconnected, open-pore network during thermal porogen removal and conversion of the preceramic polymer led to air permeabilities in the order of 10-14 m2. The materials were further exposed to long-term heat treatments to demonstrate the stability of properties after 100 h at 800 degrees C in oxidizing, inert, and reducing environments. The determined performance, in combination with the versatile preparation method, illustrates the feasibility of this processing approach for the generation of porous ceramic support structures for applications at elevated temperatures in a variety of fields, including membrane and catalysis science. PMID- 26681810 TI - Parental effects and flight behaviour in the burying beetle, Nicrophorus vespilloides. AB - Parents play a key role in determining the phenotype of their offspring. However, relatively few studies have investigated whether parents can change their offspring's behaviour in a sustained way that persists into adulthood. With experiments on the burying beetle, Nicrophorus vespilloides, we investigated how the developmental environment created by parents affects their offspring's wing morphology in adulthood, and the correlated effects on adult flight behaviour. Burying beetles exhibit complex biparental care, but offspring can survive without parental provisioning. By removing parents just prior to hatching, while holding the nutritional environment constant, we investigated the downstream consequences for offspring morphology and behaviour. Larvae that developed in the absence of their parents had relatively long and more slender wings than those that developed in their parents' presence. Flight mill tests revealed that flight performance was dependent on the presence of parents during development but not on wing shape. Our results demonstrate that parents have long-lasting effects on the behaviour of their offspring, by influencing the morphology and flight behaviour of their young even after they have matured into adults. PMID- 26681808 TI - HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function phenotype relationship. AB - Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare autosomal dominant inherited peripheral neuropathy caused by mutations in the SPTLC1 and SPTLC2 subunits of serine palmitoyltransferase (SPT). The mutations induce a permanent shift in the substrate preference from L-serine to L-alanine, which results in the pathological formation of atypical and neurotoxic 1-deoxy sphingolipids (1-deoxySL). Here we compared the enzymatic properties of 11 SPTLC1 and six SPTLC2 mutants using a uniform isotope labelling approach. In total, eight SPT mutants (STPLC1p.C133W, p.C133Y, p.S331F, p.S331Y and SPTLC2p.A182P, p.G382V, p.S384F, p.I504F) were associated with increased 1-deoxySL synthesis. Despite earlier reports, canonical activity with l-serine was not reduced in any of the investigated SPT mutants. Three variants (SPTLC1p.S331F/Y and SPTLC2p.I505Y) showed an increased canonical activity and increased formation of C20 sphingoid bases. These three mutations are associated with an exceptionally severe HSAN1 phenotype, and increased C20 sphingosine levels were also confirmed in plasma of patients. A principal component analysis of the analysed sphingoid bases clustered the mutations into three separate entities. Each cluster was related to a distinct clinical outcome (no, mild and severe HSAN1 phenotype). A homology model based on the protein structure of the prokaryotic SPT recapitulated the same grouping on a structural level. Mutations associated with the mild form clustered around the active site, whereas mutations associated with the severe form were located on the surface of the protein. In conclusion, we showed that HSAN1 mutations in SPT have distinct biochemical properties, which allowed for the prediction of the clinical symptoms on the basis of the plasma sphingoid base profile. PMID- 26681811 TI - A Distributed Ensemble Approach for Mining Healthcare Data under Privacy Constraints. AB - In recent years, electronic health records (EHRs) have been widely adapted at many healthcare facilities in an attempt to improve the quality of patient care and increase the productivity and efficiency of healthcare delivery. These EHRs can accurately diagnose diseases if utilized appropriately. While the EHRs can potentially resolve many of the existing problems associated with disease diagnosis, one of the main obstacles in effectively using them is the patient privacy and sensitivity of the medical information available in the EHR. Due to these concerns, even if the EHRs are available for storage and retrieval purposes, sharing of the patient records between different healthcare facilities has become a major concern and has hampered some of the effective advantages of using EHRs. Due to this lack of data sharing, most of the facilities aim at building clinical decision support systems using limited amount of patient data from their own EHR systems to provide important diagnosis related decisions. It becomes quite infeasible for a newly established healthcare facility to build a robust decision making system due to the lack of sufficient patient records. However, to make effective decisions from clinical data, it is indispensable to have large amounts of data to train the decision models. In this regard, there are conflicting objectives of preserving patient privacy and having sufficient data for modeling and decision making. To handle such disparate goals, we develop two adaptive distributed privacy-preserving algorithms based on a distributed ensemble strategy. The basic idea of our approach is to build an elegant model for each participating facility to accurately learn the data distribution, and then can transfer the useful healthcare knowledge acquired on their data from these participators in the form of their own decision models without revealing and sharing the patient-level sensitive data, thus protecting patient privacy. We demonstrate that our approach can successfully build accurate and robust prediction models, under privacy constraints, using the healthcare data collected from different geographical locations. We demonstrate the performance of our method using the Type-2 diabetes EHRs accumulated from multiple sources from all fifty states in the U.S. Our method was evaluated on diagnosing diabetes in the presence of insufficient number of patient records from certain regions without revealing the actual patient data from other regions. Using the proposed approach, we also discovered the important biomarkers, both universal and region specific, and validated the selected biomarkers using the biomedical literature. PMID- 26681794 TI - Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications. AB - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate "paradoxical" outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of "antioxidant" nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that "paradoxical" roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways. PMID- 26681812 TI - General Blending Models for Data From Mixture Experiments. AB - We propose a new class of models providing a powerful unification and extension of existing statistical methodology for analysis of data obtained in mixture experiments. These models, which integrate models proposed by Scheffe and Becker, extend considerably the range of mixture component effects that may be described. They become complex when the studied phenomenon requires it, but remain simple whenever possible. This article has supplementary material online. PMID- 26681813 TI - Digital Algorithmic Diabetic Retinopathy Severity Scoring System (An American Ophthalmological Society Thesis). AB - PURPOSE: To develop a new diabetic retinopathy severity scoring system and to determine if it can monitor changes from baseline as well as identify precise features that have changed over time. Such a grading system could potentially provide an understanding of the impact of treatments utilizing an algorithmic scoring technique. METHODS: The traditional ETDRS grading system was examined and a flow algorithm based on the grading approach was created. All visual comparative assessment points, relying on identification of features in relation to prior standard photographic images, were evaluated and quantified. A new grading form was created that provided fields that captured all relevant features required for determining the ETDRS grading score. A computer software algorithm was developed that examines all entered fields and calculates the appropriate diabetic severity score. RESULTS: This diabetic retinopathy scoring algorithm system was successful in generating a severity score comparable to traditional methods of grading images. Validation with traditionally graded images was performed, demonstrating that in a majority of cases, the severity scores were comparable. The algorithmic grading system was then used to analyze images obtained in a large clinical study of diabetic macular edema, resulting in data regarding baseline scoring values, as well as detailed features of the microvasculature that drove the severity scoring results, and changes seen during the trial. CONCLUSION: This new algorithmic diabetic severity scoring system provides a means to monitor the progression or regression of retinopathy with therapeutic intervention as well as assess the individual microvascular features that may be modified over the course of treatment. PMID- 26681815 TI - Quantifying global dust devil occurrence from meteorological analyses. AB - : Dust devils and nonrotating dusty plumes are effective uplift mechanisms for fine particles, but their contribution to the global dust budget is uncertain. By applying known bulk thermodynamic criteria to European Centre for Medium-Range Weather Forecasts (ECMWF) operational analyses, we provide the first global hourly climatology of potential dust devil and dusty plume (PDDP) occurrence. In agreement with observations, activity is highest from late morning into the afternoon. Combining PDDP frequencies with dust source maps and typical emission values gives the best estimate of global contributions of 3.4% (uncertainty 0.9 31%), 1 order of magnitude lower than the only estimate previously published. Total global hours of dust uplift by dry convection are ~0.002% of the dust lifting winds resolved by ECMWF, consistent with dry convection making a small contribution to global uplift. Reducing uncertainty requires better knowledge of factors controlling PDDP occurrence, source regions, and dust fluxes induced by dry convection. KEY POINTS: Global potential dust devil occurrence quantified from meteorological analyses Climatology shows realistic diurnal cycle and geographical distribution Best estimate of global contribution of 3.4% is 10 times smaller than the previous estimate. PMID- 26681814 TI - ASYMPTOTICS FOR CHANGE-POINT MODELS UNDER VARYING DEGREES OF MIS-SPECIFICATION. AB - Change-point models are widely used by statisticians to model drastic changes in the pattern of observed data. Least squares/maximum likelihood based estimation of change-points leads to curious asymptotic phenomena. When the change-point model is correctly specified, such estimates generally converge at a fast rate (n) and are asymptotically described by minimizers of a jump process. Under complete mis-specification by a smooth curve, i.e. when a change-point model is fitted to data described by a smooth curve, the rate of convergence slows down to n1/3 and the limit distribution changes to that of the minimizer of a continuous Gaussian process. In this paper we provide a bridge between these two extreme scenarios by studying the limit behavior of change-point estimates under varying degrees of model mis-specification by smooth curves, which can be viewed as local alternatives. We find that the limiting regime depends on how quickly the alternatives approach a change-point model. We unravel a family of 'intermediate' limits that can transition, at least qualitatively, to the limits in the two extreme scenarios. The theoretical results are illustrated via a set of carefully designed simulations. We also demonstrate how inference for the change-point parameter can be performed in absence of knowledge of the underlying scenario by resorting to subsampling techniques that involve estimation of the convergence rate. PMID- 26681816 TI - Message Variability and Heterogeneity: A Core Challenge for Communication Research. AB - Messages are central to human social experience, and pose key conceptual and methodological challenges in the study of communication. In response to these challenges, we outline a systematic approach to conceptualizing, operationalizing, and analyzing messages. At the conceptual level, we distinguish between two core aspects of messages: message variability (the defined and operationalized features of messages) and message heterogeneity (the undefined and unmeasured features of messages), and suggest preferred approaches to defining message variables. At the operational level, we identify message sampling, selection, and research design strategies responsive to issues of message variability and heterogeneity in experimental and survey research. At the analytical level, we highlight effective techniques to deal with message variability and heterogeneity. We conclude with seven recommendations to increase rigor in the study of communication through appropriately addressing the challenges presented by messages. PMID- 26681817 TI - Exploratory Failure Time Analysis in Large Scale Genomics. AB - In large scale genomic analyses dealing with detecting genotype-phenotype associations, such as genome wide association studies (GWAS), it is desirable to have numerically and statistically robust procedures to test the stochastic independence null hypothesis against certain alternatives. Motivated by a special case in a GWAS, a novel test procedure called correlation profile test (CPT) is developed for testing genomic associations with failure-time phenotypes subject to right censoring and competing risks. Performance and operating characteristics of CPT are investigated and compared to existing approaches, by a simulation study and on a real dataset. Compared to popular choices of semiparametric and nonparametric methods, CPT has three advantages: it is numerically more robust because it solely relies on sample moments; it is more robust against the violation of the proportional hazards condition; and it is more flexible in handling various failure and censoring scenarios. CPT is a general approach to testing the null hypothesis of stochastic independence between a failure event point process and any random variable; thus it is widely applicable beyond genomic studies. PMID- 26681818 TI - Does job complexity mitigate the negative effect of emotion-rule dissonance on employee burnout? AB - In interactions with clients or patients, human service workers are at risk of experiencing discrepancies between felt and organizationally mandated emotions (i.e. emotion-rule dissonance). Given the documented detrimental effects of such discrepancies on employee strain, the present study investigated whether job complexity mitigates the relation between emotion-rule dissonance and employee burnout using data from a two-wave panel study of eldercare workers (N = 583, 16 month time lag). Structural equation modelling revealed that emotion-rule dissonance at Time 1 preceded emotional exhaustion and depersonalization at Time 2. Beyond that, employees whose work offered job complexity were found to suffer less from emotional exhaustion and depersonalization when encountering discrepancies between felt and stipulated emotions compared to employees who conducted noncomplex work. Thus, designing complex tasks appears to be a crucial starting point for alleviating employee burnout in jobs that provoke emotion-rule dissonance. PMID- 26681819 TI - Assessment of physico-chemical properties and metal contents of water and sediments of Bodo Creek, Niger Delta, Nigeria. AB - Some physico-chemical properties and the concentrations of the metals Fe, Mn, Ni, Cd, Cr, Co, Cu, Pb, and Zn in water and sediments were examined from September 2011 to January 2012 in Bodo Creek, where oil spills have been recurrent. Temperature, pH, total dissolved solid, conductivity, salinity, dissolved oxygen, biological oxygen demand (BOD), chemical oxygen demand (COD), total hardness, sulfate, nitrate, and phosphate were determined in surface water. Particle size, total organic matter (TOM), and pH were also determined in the sediments. The parameters were within permissible limits except the mean values of BOD, COD, total hardness, and sulfate that exceeded levels permissible for domestic use. The sediments consisted mainly of sand, with TOM ranging from 0.2% to 5.5%. With the exception of cadmium that was below detection limit, metal levels (mg kg-1) in the sediments were 12 (Mn), 1070 (Fe), 10 (Cu), 10 (Zn), 5.3 (Cr), 1.1 (Pb), 1.0 (Ni), and 0.5 (Co) while in water they were 24, 98, 21, 6.9, 4.0, 0.6, 0.18, and 0.16, respectively. The latter were higher than World Health Organization recommended permissible levels for both surface and drinking water. PMID- 26681821 TI - Does a ban on informal health providers save lives? Evidence from Malawi. AB - Informal health providers ranging from drug vendors to traditional healers account for a large fraction of health care provision in developing countries. They are, however, largely unlicensed and unregulated leading to concern that they provide ineffective and, in some cases, even harmful care. A new and controversial policy tool that has been proposed to alter household health seeking behavior is an outright ban on these informal providers. The theoretical effects of such a ban are ambiguous. In this paper, we study the effect of a ban on informal (traditional) birth attendants imposed by the Malawi government in 2007. To measure the effect of the ban, we use a difference-in-difference strategy exploiting variation across time and space in the intensity of exposure to the ban. Our most conservative estimates suggest that the ban decreased use of traditional attendants by about 15 percentage points. Approximately three quarters of this decline can be attributed to an increase in use of the formal sector and the remainder is accounted for by an increase in relative/friend attended births. Despite the rather large shift from the informal to the formal sector, we do not find any evidence of a statistically significant reduction in newborn mortality on average. The results are robust to a triple difference specification using young children as a control group. We examine several explanations for this result and find evidence consistent with quality of formal care acting as a constraint on improvements in newborn health. PMID- 26681820 TI - Predictive Markers for the Recurrence of Nonmuscle Invasive Bladder Cancer Treated with Intravesical Therapy. AB - High recurrence rate is one representative characteristic of bladder cancer. Intravesical therapy after transurethral resection is often performed in patients with nonmuscle invasive bladder cancer (NMIBC) to prevent recurrence. Bacillus Calmette-Guerin (BCG) and several anticancer/antibiotic agents, such as mitomycin C and epirubicin, are commonly used for this therapy. BCG treatment demonstrates strong anticancer effects. However, it is also characterized by a high frequency of adverse events. On the other hand, although intravesical therapies using other anticancer and antibiotic agents are relatively safe, their anticancer effects are lower than those obtained using BCG. Thus, the appropriate selection of agents for intravesical therapy is important to improve treatment outcomes and maintain the quality of life of patients with NMIBC. In this review, we discuss the predictive value of various histological and molecular markers for recurrence after intravesical therapy in patients with NMIBC. PMID- 26681822 TI - Friend or foe: inter-specific interactions and conflicts of interest within the family. AB - Interactions between species can vary from mutually beneficial to evolutionarily neutral to antagonistic, even when the same two species are involved. Similarly, social interactions between members of the same species can lie on a spectrum from conflict to cooperation.The aim of the present study was to investigate whether variation in the two types of social behaviour are interconnected. Is the fitness of the various classes of social partner within species (such as parent and offspring, or male and female) differently affected by interactions with a second species? Moreover, can inter-specific interactions influence the outcome of social interactions within species?The present experiments focus on the interactions between the burying beetle Nicrophorus vespilloides Herbst and the phoretic mite Poecilochirus carabi G. Canestrini & R. Canestrini. The approach was to measure the fitness of burying beetle mothers, fathers, and offspring after reproduction, which took place either in the presence or absence of mites.We found that male, female, and larval burying beetles derive contrasting fitness costs and benefits from their interactions with the mite, despite sharing a common family environment. From the mite's perspective, its relationship with the burying beetle can, therefore, be simultaneously antagonistic, neutral, and possibly even mutualistic, depending on the particular family member involved. We also found that mites can potentially change the outcome of evolutionary conflicts within the family.We conclude that inter-specific interactions can explain some of the variation in social interactions seen within species. It is further suggested that intra-specific interactions might contribute to variation in the outcome of interactions between species. PMID- 26681823 TI - Association of Bacterial vaginosis and other Sexually Transmitted Infections with HIV among pregnant women in Nigeria. AB - OBJECTIVES: To determine the association of Bacterial vaginosis (BV) and other sexually transmissible infections (STIs) with HIV prevalence among pregnant women in Jos, Nigeria. METHODS: This was a cross- sectional study of pregnant women who participated in the Prevention of Mother-to-Child Transmission of HIV program of the AIDS Prevention Initiative in Nigeria, between April 2002 and July 2004, at the Jos University Teaching Hospital in Jos, Nigeria. Blood, high vaginal and endocervical samples were obtained for diagnosis of HIV, BV and other STIs. Data were analyzed for prevalence of HIV, BV and other STIs. Univariate and multivariate logistic regression models generated unadjusted and adjusted odds ratios (OR) as well as 95% confidence intervals (CI) of the association of BV and other STIs with HIV prevalence. P value <0.05 was considered statistically significant. RESULTS: A total of 4,046 pregnant women were studied and 97.6% (3,950/4,046) had complete laboratory records for analysis. The prevalence of HIV was 8.2% (CI: 7.4-9.1); BV 11.9% (CI: 10.9-12.9); Candida 10.7% (CI: 9.7-11.7); mixed infection of BV and Candida 2.8% (CI: 2.3-3.4); Trichomonads 0.6% (CI: 0.3 0.8) and syphilis 0.35% (0.16-0.54). BV, Candida, mixed BV and Candida; and Trichomonads were independently associated with HIV infection [adjusted OR (95% CI), 2.9 (CI: 2.2-3.9); 2.0 (CI: 1.5-2.9); 3.4 (CI: 2.0-5.6), and 3.3 (CI: 1.1 9.7) respectively]. CONCLUSION: HIV prevalence is higher among pregnant women who have BV, Candida and Trichomonads vaginal infections compared with women who have no evidence of infection. The practice of routine screening for BV and other STIs among pregnant women as a strategy for identifying women at risk for prevalent HIV infection should be sustained/ encouraged and the syndromic management of STIs should be integrated into all antenatal care management protocols in antenatal clinics in order to curb the epidemic of heterosexual HIV transmission. PMID- 26681824 TI - Prevalence and Correlates of Intimate Partner Violence among Male Civil Servants in Ibadan, Nigeria. AB - BACKGROUND: Intimate Partner violence (IPV) is one of the common forms of violence against women and is a global public health problem that transcends social, economic, religious and cultural groups. It is often perceived as a private problem or a normal part of life but it contributes greatly to morbidity and mortality. OBJECTIVE: To assess the prevalence and correlates of intimate partner violence by male civil servants in Oyo State Secretariat Ibadan, Nigeria. METHODS: A cross-sectional study was conducted using a multi-stage sampling technique. A total of 609 respondents completed a pre-tested self-administered questionnaire. Data were analysed using SPSS version 18 and STATA version 12. Chi square statistic was used to test associations between categorical variables and predictors of perpetration of intimate partner violence were determined using logistic regression model at a level of statistical significance of 5%. RESULT: The mean age was 38.8+/-9.9 years and about 74.5% were married. The prevalence of IPV perpetration in the 12 months preceding the study was 66.0%. The prevalence of controlling behaviour was 52.2%, psychological abuse - 31.2%, sexual violence 23.0%, and physical violence - 11.7%. The predictors of perpetrating any form of IPV included previous history of physical fight with another woman [OR: 2.4 (95% CI: 1.30-3.40)], having a negative attitude towards wife beating [OR 2.5 [95% CI: 1.85-3.42], childhood exposure to parental IPV [OR: 2.1 (95% CI: 1.30-3.41)] and use of alcohol [OR: 1.6 (95% CI: 1.14-2.15]. CONCLUSION: The different types of IPV were prevalent among the male civil servants, despite their educational status. Strategies to stop IPV should include male education to change attitudes that encourage violence in relationships to use of non-violent conflict resolution strategies. Education should also include the dangers of alcohol abuse and involvement in physical fights. PMID- 26681825 TI - Influence of Internet Accessibility and Demographic factors on utilization of Web based Health Information Resources by Resident Doctors in Nigeria. AB - BACKGROUND: The internet is a huge library with avalanche of information resources including healthcare information. There are numerous studies on use of electronic resources by healthcare providers including medical practitioners however, there is a dearth of information on the patterns of use of web-based health information resource by resident doctors in Nigeria. This study therefore investigates the influence of internet accessibility and demographic factors on utilization of web-based health information resources by resident doctors in tertiary healthcare institutions in Nigeria. METHODS: Descriptive survey design was adopted for this study. The population of study consisted of medical doctors undergoing residency training in 13 tertiary healthcare institutions in South West Nigeria. The tertiary healthcare institutions were Federal Medical Centres, University Teaching Hospitals and Specialist Hospitals (Neuropsychiatric and Orthopaedic). A pre-tested, self-administered questionnaire was used for data collection. The Statistical Package for the Social Sciences (SPSS) was used for data analysis. Data were analyzed using descriptive statistics, Pearson Product Moment correlation and multiple regression analysis. RESULTS: The mean age of the respondents was 34 years and males were in the majority (69.0%). A total of 96.1% respondents had access to the Internet. E-mail (X=5.40, SD=0.91), Google (X=5.26, SD=1.38), Yahoo (X=5.15, SD=4.44) were used weekly by the respondents. Preparation for Seminar/Grand Round presentation (X=8.4, SD=1.92), research (X=7.8, SD=2.70) and communication (X=7.6, SD=2.60) were ranked high as purposes for use of web-based information resources. There is a strong, positive and significant relationship between internet accessibility and utilization of web based health information resources (r=0.628, p<0.05). Internet accessibility (B=0.911) and demographic factors: gender (B=-2.027), designation (B=-0.343) educational qualification (B=2.411) significantly influence utilization of web based health information resources of the respondents. CONCLUSION: A great majority of the respondents have access to the Internet and used web-based health information resources more for academic purposes than patient care. Training is required to promote use of internet health information resources among resident doctors. The findings of this study will be useful to the management of the 13 healthcare institutions regarding provision of appropriate internet facilities that will enhance access and use of web-based health information resources by resident doctors. PMID- 26681826 TI - In vitro evaluation of the antioxidant potential, phenolic and flavonoid contents of the stem bark ethanol extract of Anogeissus leiocarpus. AB - Plant-derived antioxidants with free radical scavenging activities can be relevant as chemopreventive agents against the numerous diseases associated with free radicals and reactive oxygen species. Some phytoconstituents possess antioxidant activities in biological systems. On this basis, we evaluated the antioxidant potential, and determined the total phenolic and flavonoid contents of the ethanol extract of the stem bark of Anogeissus leiocarpus [EESAL]. Antioxidant assays carried out include: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phosphomolybdate, beta-carotene bleaching, ferric reducing, and hydroxyl radical scavenging activities. Results of DPPH assay showed no significant difference (p < 0.001) between EESAL and butylated hydroxyanisole [BHA], while EESAL exhibited a significantly (p < 0.001) higher activity than BHT [butylated hydroxytoluene]. Phosphomolybdate method recorded a total antioxidant capacity of 190.00 +/- 70.53 ug butylated hydroxytoluene equivalents [BHTE]/mg dry extract, while beta-carotene bleaching assay gave percent antioxidant activities of both EESAL and BHT as 81.46+/-1.62 and 80.90+/-1.39 respectively. Ferric reducing abilities of both EESAL and ascorbic acid increased in a concentration-dependent manner with EESAL displaying a significantly (p < 0.001) higher reductive activity than vitamin C. EESAL displayed a significantly higher hydroxyl radical scavenging activity as compared with BHT at the lowest concentration with no significant difference at the highest concentration. Total phenolic and flavonoid contents of EESAL were obtained as 608.10 +/- 2.12 ug GAE/mg and 78.96 +/- 3.37 ug QE/mg respectively. Taken together, the free radical scavenging and antioxidant activity of EESAL is likely due to its high phenolic content with complementary effects of the flavonoid components. PMID- 26681827 TI - New results on the hydrodynamic behaviour of fossil Nummulites tests from two nummulite banks from the Bartonian and Priabonian of northern Italy. AB - Settling velocities of 58 well-preserved tests of fossil Nummulites were experimentally determined using a settling tube. The tests were collected from the nummulite banks of Pederiva di Grancona (A forms of N. lyelli and N. striatus, Middle Eocene) and San Germano dei Berici (A and B forms of N. fabianii, Late Eocene), both in the Berici Mts. (Veneto, northern Italy). The data were compared with estimated settling velocities that the same specimens might have had in life conditions. This was done by reconstructing their densities simulating water-filled condition and, to simulate post-diagenetic effects, under calcite-filled condition. These simulations show that A and B forms, even if they greatly diverge in shape, volume and size, still possess comparable settling velocities, and that each nummulite bank is characterized by specific hydrodynamic parameters. The use of settling velocity as a parameter to quantify the hydrodynamic behaviour of particles in seawater enables estimation of palaeoenvironmental conditions such as depth, substrate and the energy scenario. Such information is useful in obtaining further insights into the genesis of nummulite banks, the autochthony or allochthony of which is still being debated. Our results point to an autochthonous interpretation. PMID- 26681828 TI - Salivary alpha amylase and salivary cortisol response to fluid consumption in exercising athletes. AB - The objective of the study was to examine salivary biomarker response to fluid consumption in exercising athletes. Exercise induces stress on the body and salivary alpha amylase (sAA) and salivary cortisol are useful biomarkers for activity in the sympathoadrenal medullary system and the hypothalamic pituitary adrenal axis which are involved in the stress response. Fifteen college students were given 150 ml and 500 ml of water on different days and blinded to fluid condition. The exercise protocol was identical for both fluid conditions using absolute exercise intensities ranging from moderate to high. Saliva was collected prior to exercise, post moderate and post high intensities and analyzed by Salimetrics assays. Exercise was significant for sAA with values different between pre-exercise (85 +/- 10 U . ml(-1)) and high intensity (284 +/- 30 U . ml(-1)) as well as between moderate intensity (204 +/- 32 U . ml(-1)) and high intensity. There was no difference in sAA values between fluid conditions at either intensity. Exercise intensity and fluid condition were each significant for cortisol. Cortisol values were different between pre-exercise (0.30 +/- 0.03 ug . dL(-1)) and high intensity (0.45 +/- 0.05 ug . dL(-1)) as well as between moderate intensity (0.33 +/- 0.04 ug . dL(-1)) and high intensity. Moderate exercise intensity cortisol was lower in the 500 ml condition (0.33 +/- 0.03 ug . dL(-1)) compared with the 150 ml condition (0.38 +/- 0.03 ug . dL(-1)). This altered physiological response due to fluid consumption could influence sport performance and should be considered. In addition, future sport and exercise studies should control for fluid consumption. PMID- 26681829 TI - Vitamin D status and determinants of deficiency in non-supplemented athletes during the winter months in Tunisia. AB - Recent reports suggest that hypovitaminosis D in athletes is as common as in the general population. This study was devised to examine vitamin D status and determinants of deficiency in athletes living in a sunny country (Tunisia). One hundred and fifty national elite athletes, training outdoors (n = 83) or indoors (n = 67), were enrolled from January to February 2012. Plasma 25-hydroxyvitamin D was measured by radioimmunoassay. Concentrations were between 50 and 75 nmol . l( 1) in 21.3% of participants, between 25 and 50 nmol . l(-1) in 55.3% of participants and <25 nmol . l(-1) in 14.7% of participants. The concentrations were significantly lower in indoor athletes than outdoor athletes (36.2+/-19.0 nmol . l(-1) vs. 49.1+/-19.2 nmol . l(-1); p < 0.001). In multivariate analysis, vitamin D deficiency (25-hydroxyvitamin D <50 nmol . l(-1)) was associated with indoor sports [multi-adjusted odds ratio (95% confidence interval), 5.03 (1.64 15.4); p = 0.005], female gender [3.72 (1.44-9.65); p = 0.007] and age < 18 years [2.40 (1.01-5.85); p = 0.05]. Athletes living in sun-rich environments are exposed to a high risk of vitamin D inadequacy. Given the importance of vitamin D in health and athletic ability, targeting sufficient levels of plasma 25 hydroxyvitamin D in athletes is well justified. PMID- 26681830 TI - Similar hypotensive responses to resistance exercise with and without blood flow restriction. AB - Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 +/- 4 years, 74 +/- 3 kg, 174 +/- 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. PMID- 26681831 TI - Long-term treadmill exercise improves spatial memory of male APPswe/PS1dE9 mice by regulation of BDNF expression and microglia activation. AB - Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer's disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of beta-amyloid, brain derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of beta-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of beta-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect. PMID- 26681832 TI - Soccer vs. running training effects in young adult men: which programme is more effective in improvement of body composition? Randomized controlled trial. AB - The aims of this study were: 1) To determine the effects of a 12-week recreational soccer training programme and continuous endurance running on body composition of young adult men and 2) to determine which of these two programmes was more effective concerning body composition. Sixty-four participants completed the randomized controlled trial and were randomly assigned to one of three groups: a soccer training group (SOC; n=20), a running group (RUN; n=21) or a control group performing no physical training (CON; n=23). Training programmes for SOC and RUN lasted 12-week with 3 training sessions per week. Soccer sessions consisted of 60 min ordinary five-a-side, six-a-side or seven-a-side matches on a 30-45 m wide and 45-60 m long plastic grass pitch. Running sessions consisted of 60 min of continuous moderate intensity running at the same average heart rate as in SOC (~80% HRmax). All participants, regardless of group assignment, were tested for each of the following dependent variables: body weight, body height, body mass index, percent body fat, body fat mass, fat-free mass and total body water. In the SOC and RUN groups there was a significant decrease (p < 0.05) in body composition parameters from pre- to post-training values for all measures with the exception of fat-free mass and total body water. Body mass index, percent body fat and body fat mass did not differ between groups at baseline, but by week 12 were significantly lower (p < 0.05) in the SOC and RUN groups compared to CON. To conclude, recreational soccer training provides at least the same changes in body composition parameters as continuous running in young adult men when the training intensity is well matched. PMID- 26681833 TI - Sprint interval training (SIT) is an effective method to maintain cardiorespiratory fitness (CRF) and glucose homeostasis in Scottish adolescents. AB - The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 +/- 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 +/- 0.6 yrs). CRF (VO2max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P < 0.01) with non-significant trends for fasting insulin (P= 0.08), and HOMA-IR (P=0.06). CRF decreased (P < 0.01) in SPE such that POST intervention CRF was significantly lower (P< 0.05) in SPE. Fasting plasma glucose (P < 0.01), insulin (P< 0.01) and HOMA-IR (P< 0.01) increased significantly amongst SPE. The main finding of the present study is that 7-weeks of SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term. PMID- 26681834 TI - The relationship of aerobic capacity, anaerobic peak power and experience to performance in CrossFit exercise. AB - CrossFit is becoming increasingly popular as a method to increase fitness and as a competitive sport in both the Unites States and Europe. However, little research on this mode of exercise has been performed to date. The purpose of the present investigation involving experienced CrossFit athletes and naive healthy young men was to investigate the relationship of aerobic capacity and anaerobic power to performance in two representative CrossFit workouts: the first workout was 12 minutes in duration, and the second was based on the total time to complete the prescribed exercise. The participants were 32 healthy adult males, who were either naive to CrossFit exercise or had competed in CrossFit competitions. Linear regression was undertaken to predict performance on the first workout (time) with age, group (naive or CrossFit athlete), VO2max and anaerobic power, which were all significant predictors (p < 0.05) in the model. The second workout (repetitions), when examined similarly using regression, only resulted in CrossFit experience as a significant predictor (p < 0.05). The results of the study suggest that a history of participation in CrossFit competition is a key component of performance in CrossFit workouts which are representative of those performed in CrossFit, and that, in at least one these workouts, aerobic capacity and anaerobic power are associated with success. PMID- 26681835 TI - Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males. AB - The relationship between oxidative stress and some exercise components of resistance exercise (e.g. intensity, exercise volume) has not been clearly defined. Additionally, the oxidative stress markers may respond differently in various conditions. This study aims to determine the effects of progressive intensity of resistance exercise (RE) on oxidative stress and antioxidants in trained and untrained men, and also to investigate the possible threshold intensity required to evoke oxidative stress. RE trained (N=8) and untrained (N=8) men performed the leg extension RE at progressive intensities standardized for total volume: 1x17 reps at 50% of one-repetition maximum (1RM); 1x14 reps at 60% of 1RM; 1x12 reps at 70% of 1RM; 2x5 reps at 80% of 1RM; and 3x3 reps at 90% of 1RM. Blood samples were drawn before (PRE) and immediately after each intensity, and after 30 minutes, 60 minutes and 24 hours following the RE. Lipid hydroperoxide (LHP) significantly increased during the test and then decreased during the recovery in both groups (p<0.05); the POST-24 h LHP level was lower than PRE-LHP. Protein carbonyl (PCO) and superoxide dismutase (SOD) significantly increased (p<0.05); however, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and glutathione (GSH) were not affected by the RE (p > 0.05). The results indicated that there was no significant training status x intensity interaction for examined variables (p > 0.05). Standardized volume of RE increased oxidative stress responses. Our study suggests that lower intensity (50%) is enough to increase LHP, whereas higher intensity (more than 80%) is required to evoke protein oxidation. PMID- 26681836 TI - Late Oligocene and Early Miocene Muroidea of the Zinda Pir Dome. AB - A series of Oligocene through Early Miocene terrestrial deposits preserved in the foothills of the Zinda Pir Dome of western Pakistan produce multiple, superposed fossil mammal localities. These include small mammal assemblages that shed light on the evolution of rodent lineages, especially Muroidea, in South Asia. Nine small mammal localities span approximately 28-19 Ma, an interval encompassing the Oligocene-Miocene boundary. The Early Miocene rodent fossil assemblages are dominated by muroid rodents, but muroids are uncommon and archaic in earlier Oligocene horizons. The Zinda Pir sequence includes the evolutionary transition to modern Muroidea at about the Oligocene-Miocene boundary. We review the muroid record for the Zinda Pir Dome, which includes the early radiation of primitive bamboo rats (Rhizomyinae) and early members of the modern muroid radiation, which lie near crown Cricetidae and Muridae. The Zinda Pir record dates diversification of modern muroids in the Indian Subcontintent and establishment by 19 Ma of muroid assemblages characteristic of the later Siwaliks. PMID- 26681837 TI - Supporting Family Engagement in Home Visiting with the Family Map Inventories. AB - The purpose of this study was to examine the feasibility and usefulness of a universal screening tool, the Family Map Inventory (F MI), to assess family strengths and needs in a home visiting program. The FMI has been used successfully by center-based early childcare programs to tailor services to family need and build on existing strengths. Home visiting coordinators (N = 39) indicated the FMI would provide useful information, and they had the capacity to implement. In total, 70 families who enrolled in a Home Instruction for Parents of Preschool Youngsters (HIPPY) program were screened by the coordinator. The results of the FMI provided meaningful information about the home and parenting environment. Overall, most caregivers provided high levels of school readiness and parental warmth and low levels of family conflict and parenting stress. On the other hand, many families did not provide adequate food quality, exhibited chaotic home environments, and practiced negative discipline. This study demonstrated that the FMI is a feasible and useful option to assess comprehensive family needs in home visiting programs. It also demonstrated that the FMI provided home visiting coordinators a system to measure family strengths and needs. This could provide an assessment of program effectiveness and changes in the family's environment. PMID- 26681838 TI - UV-assisted room-temperature chemiresistive NO2 sensor based on TiO2 thin film. AB - TiO2 thin film based, chemiresistive sensors for NO2 gas which operate at room temperature under ultraviolet (UV) illumination have been demonstrated in this work. The rf-sputter deposited and post-annealed TiO2 thin films have been characterized by atomic force microscopy, X-ray photoelectron spectroscopy, and X ray diffraction to obtain surface morphology, chemical state, and crystal structure, respectively. UV-vis absorption spectroscopy and Tauc plots show the optical properties of the TiO2 films. Under UV illumination, the NO2 sensing performance of the TiO2 films shows a reversible change in resistance at room temperature. The observed change in electrical resistivity can be explained by the modulation of surface-adsorbed oxygen. This work is the first demonstration of a facile TiO2 sensor for NO2 analyte that operates at room-temperature under UV illumination. PMID- 26681840 TI - Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet. AB - BACKGROUND: This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5(-/-)), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice. RESULTS: TLR5(-/-) and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5(-/ ) mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5(-/-) mice. In addition, the LFD-fed TLR5(-/-) mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice. CONCLUSIONS: This study demonstrated that TLR5 gene knockout impairs some effects of weight reduction in DIO. PMID- 26681839 TI - Linking Endotoxins, African Dust PM10 and Asthma in an Urban and Rural Environment of Puerto Rico. AB - African Dust Events (ADE) are a seasonal phenomenon that has been suggested to exacerbate respiratory and proinflammatory diseases in Puerto Rico (PR). Increases in PM10 concentration and the effects of biological endotoxins (ENX) are critical factors to consider during these storms. ENX promote proinflammatory responses in lungs of susceptible individuals through activation of the Toll-like receptors (TLR2/4) signaling pathways. The objective of the study was to evaluate the toxicological and proinflammatory responses stimulated by ADE PM10 ENX reaching PR using human bronchial epithelial cells. PM10 organic extracts from a rural and urban site in PR (March 2004) were obtained from ADE and non-ADE and compared. A retrospective data analysis (PM10 concentration, aerosol images, and pediatric asthma claims) was performed from 2000 to 2012 with particular emphasis in 2004 to classify PM samples. Urban extracts were highly toxic, proinflammatory (IL-6/IL-8 secretion), and induced higher TLR4 expression and NF-kappaB activation compared to rural extracts. ENX were found to contribute to cytotoxicity and inflammatory responses provoked by urban ADE PM10 exposure suggesting a synergistic potency of local and natural ENX incoming from ADE. The contribution of ADE PM10 ENX is valuable in order to understand interactions and action mechanisms of airborne pollutants as asthma triggers in PR. PMID- 26681841 TI - Mediators of Inflammation in Myeloproliferative Neoplasms: State of the Art. PMID- 26681843 TI - Foreword. PMID- 26681842 TI - Smokeless tobacco use in Urban Indian women: Prevalence and predictors. AB - CONTEXT: India is the second largest consumer of tobacco. Tobacco consumption in nonsmoking forms is culturally accepted even among women. AIMS: This study aimed at understanding the patterns and predictors of smokeless tobacco (SLT) use among the urban low-socioeconomic women in Mumbai, India. MATERIALS AND METHODS: This is a cross-sectional community-based survey of tobacco usage among women residing in seven low-socioeconomic communities in suburbs of Mumbai, India. Staff for the study was recruited, trained, clusters selected, accurately mapped, households identified, meetings held with community leaders, and household surveys conducted. Women using tobacco were invited to participate in the detailed survey and interviewed to document the various sociodemographic factors and in depth information on tobacco use. The data were computerized and analyzed. RESULTS: About 22.30% of the total female population consumed tobacco, mainly in the smokeless forms, with only 0.50% of the tobacco users using smoked tobacco. Masheri was the most common form of tobacco used, followed by chewing tobacco. The median frequency of use of different tobacco products varied from 2 to 4 per day. The mean age at initiation of tobacco was 26.23 years. According to the results of univariate and multivariate logistic regression analysis, illiterate women, with advancing age, belonging to Hindu, Muslim, or Buddhist communities, who were either manual laborers or housewives, divorced or separated, and speaking Marathi were at higher risk of being tobacco user. CONCLUSION: Patterns and predictors of SLT use among women have been identified in the present study. This will guide in planning prevention and control strategies. PMID- 26681844 TI - Creativity is intelligence. PMID- 26681845 TI - Diagnostic perspective of saliva in insulin dependent diabetes mellitus children: An in vivo study. AB - BACKGROUND AND OBJECTIVES: The absence, destruction, or loss of beta-cells of pancreas results in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]). Presently, diagnosis and periodic monitoring of diabetes is achieved by evaluating blood glucose levels as it is relatively invasive and dreaded by children. In the light of this, present study was planned to compare salivary glucose values with blood glucose values and the biochemical characteristics of saliva in IDDM children were evaluated and obtained results were compared with the salivary parameters of normal children. MATERIALS AND METHODS: Thirty IDDM children and 30 healthy children were selected for the study. Fasting blood sample and unstimulated salivary sample were collected from all the subjects and were subjected for analysis. RESULTS: A weak positive correlation was noticed between fasting blood glucose and salivary glucose values in IDDM children. But a mean average of salivary glucose was high in IDDM children when compared with healthy children. The biochemical parameters like acid phosphatase, total protein count, and alpha-amylase were increased, whereas salivary urea did not show significant variation between the groups. CONCLUSION: With presently used diagnostic armamentarium, estimation of salivary glucose cannot replace the standard method of estimation of glucose in diabetic mellitus children. The established relationship was very weak with many variations. PMID- 26681846 TI - Growth changes in the soft tissue profile of Yemenis females: A cross-sectional study. AB - AIM: To investigate the changes in soft tissue parameters of three age groups of untreated Yemenis females. MATERIALS AND METHODS: The sample comprised 300 Yemeni females which were randomly selected and divided according to age into three equal groups (Group I: 7.34 +/- 0.65 years [prepubertal], Group II: 11.11 +/- 1.07 years [pubertal], and Group III: 22.17 +/- 3.04 years [postpubertal]). Lateral cephalometric radiographs were taken for each subject, and soft tissue measurements were performed. Comparison between the three groups was done. One cephalogram representing the mean of its group was selected from the three groups; the selected three cephalograms (one from each group) were superimposed for growth changes evaluation. RESULTS: Linear, as well as angular soft tissue measurements were significant for all measurements between the different age groups except Ls-Sn Pog', Li-Sn Pog', GSn Pog' and nasolabial angle, respectively. CONCLUSION: The identified changes with growth in Yemeni females having Class I skeletal and dental relationship should be considered during planning for orthodontic and/or orthognathic treatments. PMID- 26681847 TI - Management of symptomatic erosive-ulcerative lesions of oral lichen planus in an adult Egyptian population using Selenium-ACE combined with topical corticosteroids plus antifungal agent. AB - AIM: Oral lichen planus (OLP) is a chronic mucocutaneous disease with an immunological etiology. This study was conducted to evaluate the effect of selenium combined with Vitamins A, C & E (Selenium-ACE) in the treatment of erosive-ulcerative OLP as an adjunctive to topical corticosteroids plus antifungal agent. SUBJECTS AND METHODS: Thirty patients with a confirmed clinical and histopathologic diagnosis of OLP participated in this clinical trial. Patients were randomly allocated into one of three groups and treated as follows: (I) Topical corticosteroids, (II) topical corticosteroids plus antifungal, and (III) SE-ACE combined with topical corticosteroids plus antifungal. The patients were followed for 6 weeks. The pain and severity of the lesions were recorded at the initial and follow-up visits. All recorded data were analyzed using paired t test and ANOVA test. A P <= 0.05 was considered significant. RESULTS: The experimental groups showed a marked reduction in pain sensation and size of lesions, particularly in the final follow-up period, but there was no significant difference between the first two Groups I and II. However, healing of lesions and improvement of pain sensation was effective in Group III since a significant difference was found favoring Group III over both Groups I and II. CONCLUSION: No significant difference was found in treating erosive-ulcerative lesions of OLP by topical corticosteroids alone or combined with antifungal. However, when using SE ACE in combination with topical corticosteroids plus antifungal, this approach may be effective in managing ulcerative lesions of OLP; but more research with a larger sample size and a longer evaluation period may be recommended. PMID- 26681848 TI - Assessment of salivary calcium, phosphate, magnesium, pH, and flow rate in healthy subjects, periodontitis, and dental caries. AB - AIM: This study was conducted to estimate and compare inorganic salivary calcium, phosphate, magnesium, salivary flow rate, and pH of unstimulated saliva and oral hygiene status of healthy subjects, subjects with periodontitis and dental caries, and to correlate salivary calcium level with number of intact teeth. MATERIALS AND METHODS: The study population consisted of 48 systemically healthy subjects in the age group of 18-55 years, which was further divided into three groups: healthy, periodontitis, and dental caries. Oral hygiene index-simplified, probing pocket depth, clinical attachment level, the number of intact teeth, and active carious lesions were recorded. Estimation of inorganic salivary calcium, phosphate, and magnesium was performed spectrophotometrically using Vitros 5.1 FS. Statistical analysis was performed using the one-way analysis of variance test at 5% significance level. RESULTS: There was a statistically significant increase in inorganic salivary calcium, phosphate, pH, flow rate, and poor oral hygiene status in periodontitis group compared to dental caries and healthy group. CONCLUSION: Subjects with increased inorganic salivary calcium, phosphate, pH, flow rate, and poor oral hygiene are at a higher risk of developing periodontitis. Since there is increased remineralization potential, these subjects have more number of intact teeth compared to the dental caries group. PMID- 26681849 TI - Effect of three nanobiomaterials on the surface roughness of bleached enamel. AB - BACKGROUND: The ever-increasing demand for enhanced esthetic appearance has resulted in significant developments in bleaching products. However, the enamel surface roughness (SR) might be negatively affected by bleaching agents. This in vitro study was undertaken to compare the effects of three nanobiomaterials on the enamel SR subsequent to bleaching. MATERIALS AND METHODS: The crowns of six extracted intact nonerupted human third molars were sectioned. Five dental blocks measuring 2 mm * 3 mm * 4 mm were prepared from each tooth and placed in colorless translucent acrylic resin. The enamel areas from all the specimens were divided into five groups (n = 6): Group 1 did not undergo any bleaching procedures; Group 2 was bleached with a 40% hydrogen peroxide (HP) gel; Groups 3, 4, and 5 were bleached with a 40% HP gel modified by bioactive glass (BAG), amorphous calcium phosphate, and hydroxyapatite, respectively. The enamel SR was evaluated before and after treatment by atomic force microscopy. The data were analyzed by Kruskal-Wallis and Mann-Whitney tests. RESULTS: SR increased significantly in the HP group. SR decreased significantly in the HP gel modified by BAG group as compared to other groups. CONCLUSIONS: Within the limitations of this study, incorporation of each one of the three test biomaterials proved effective in decreasing enamel SR subsequent to in-office bleaching technique. PMID- 26681850 TI - Effect of storage time and framework design on the accuracy of maxillary cobalt chromium cast removable partial dentures. AB - STATEMENT OF PROBLEM: Inaccuracies in the fit of palatal major connectors may be related to distortion of the wax pattern due to prolonged storage time and faulty major connector design. PURPOSE: This in vitro study was carried out to find out the effect of storage time and major connector design on the accuracy of cobalt chromium cast removable partial dentures (RPDs). MATERIALS AND METHODS: A brass metal die with a Kennedy Class III, modification 1, the partially edentulous arch was used as a master die. Thirty-six refractory casts were fabricated from the master die. The refractory casts were divided into three groups (Group I: Anterior-posterior palatal bar, Group II: Palatal strap and Group III: Palatal plate) based on the design of maxillary major connector and subdivided into four groups (sub Group A: 01 h, sub Group B: 03 h, Sub Group C: 06 h, and sub Group D: 24 h) based on the storage time. For each group, 12 frameworks were fabricated. The influence of wax pattern storage time and the accuracy of the fit palatal major connector designs on the master die were compared. Casting defects (nodules/incompleteness) of the frameworks were also evaluated before finishing and polishing. Repeated measures analysis of variance was used to analyze the data. RESULTS: The gap discrepancy was least in sub Group A (01 h) followed by sub Group B (03 h) and C (06 h) and most in sub Group D (24 h). Statistically significant differences (P < 0.05 in all locations L1-L5) in the fit of the framework were related to the design of the major connector. The gap discrepancy was least in Group I (anterior-posterior palatal bar) followed by Group II (palatal strap) and most in Group II (palatal plate). CONCLUSIONS: It is recommended that the wax patterns for RPD to be invested immediately on completion of the wax procedure. The selection of a major connector design is crucial for an accurate fit of RPD. PMID- 26681851 TI - Efficacy of a comprehensive dental education program regarding management of avulsed permanent teeth as a valid indicator of increased success rate of treatment of avulsion in a North Indian population. AB - AIMS: To assess whether educating the parents, teachers, and intermediate school children of Amritsar city about the emergency management of tooth avulsion was an effective method of increasing success rate of treatment of avulsion. SUBJECTS AND METHODS: Self-administered questionnaires were prepared for 200 parents, teachers, and for intermediate school children to assess baseline knowledge. Sociodemographic distribution of the targeted group was carried out applying Kuppuswamy scale. Two months later, flip cards and posters were distributed to the selected sample followed by a reinforcement session conducted after 1 month in the form of slide presentations on dental trauma. After 3 months, reassessment performance was distributed to the same participants for reassessing any change in baseline knowledge. Further analysis of knowledge, attitude, and practices were carried out after 6 months. The scores based on Likert scale ranging 0-3 were obtained and put to statistical analysis to analyze efficacy of this program 12 months from baseline data. RESULTS AND CONCLUSION: Wilcoxon signed ranked test was applied to nonparametric data to study the knowledge before and after education was carried out. There was a significant change in the knowledge level of children, teachers, and parents after the campaign and teachers showed more positive change in the practice of emergency management of tooth avulsion, endorsing the fact that comprehensive dental education programs targeting school teachers and children can change the perspective of individuals toward treatment needs for dental trauma involving avulsion. PMID- 26681852 TI - Comparative evaluation of free gingival graft and AlloDerm((r)) in enhancing the width of attached gingival: A clinical study. AB - BACKGROUND: The presence of an adequate width of keratinized tissue is important to maintain a healthy dentogingival junction. In case of inadequate width of attached gingiva, the gingival augmentation procedure has been performed classically using the patient's own masticatory mucosa and more recently, using an acellular dermal allograft as the donor material. AIMS: The aim of the clinical study was to evaluate and compare the effectiveness of free gingival graft (FGG) and acellular dermal matrix (ADM) allograft in the ability to increase the zone of attached gingiva. MATERIALS AND METHODS: Fifteen patients with 30 sites showing the inadequate width of attached gingiva (<=1 mm) were enrolled for the split-mouth study. The width of keratinized gingiva and other clinical parameters were recorded at baseline and 12(th) month postoperatively. STATISTICAL ANALYSIS: The difference in clinical parameters within the group was assessed by Wilcoxon signed rank test. However, Mann-Whitney U-test was used to analyze the differences between test and control groups. RESULTS: The width of attached gingiva increased significantly (P < 0.01) following both the treatments but comparatively lesser gain with ADM allograft (2.13 mm vs. 4.8 mm). ADM site had significantly more shrinkage (76.6%) than FGG site (49.7%). Though FGG was found to be more effective, clinicians can prefer ADM allograft because of its certain advantages over the FGG. CONCLUSION: ADM allograft has resulted in sufficient increase in width of attached gingiva although lesser than FGG. Considering the disadvantages of FGG, it can be concluded that ADM allograft can be used as an alternative to FGG in increasing width of attached gingival in certain clinical situations. PMID- 26681853 TI - Sex assessment efficacy of permanent maxillary first molar cusp dimensions in Indians. AB - BACKGROUND: The human first maxillary molar provides clues about evolution and is functionally important. It has four main cusps, and each cusp has an independent growth pattern and different evolutionary background. Though less explored, the analysis based on measurement of each cusp appears to be more meaningful biologically than conventional measurements of the whole crown. AIM: This study aimed to demonstrate the extent of sexual dimorphism in permanent maxillary first molar cusp diameters and their potential utility in sex prediction among Indians using logistic regression analysis (LRA). MATERIALS AND METHODS: The mesiodistal and buccolingual (BL) crown diameters along with cusp dimensions and cusp indices of right maxillary first molar were measured in an Indian sample (149 males, 151 females; age range of 18-30 years). The possible sex dimorphism in these parameters was evaluated, and LRA was performed to ascertain their usefulness in sex prediction. RESULTS: BL crown dimension and the hypocone (distolingual) cusp showed the highest sexual dimorphism. The combination of metacone and hypocone, i.e., distal cusp diameters among cusp parameters showed the highest accuracy (61.3%). While, on combining all the crown and cusp diameters together the overall accuracy was raised (64.3%). CONCLUSION: This study supports the ontogeny hypothesis suggesting that early-forming mesial cusps demonstrate less sexual variation as compared to subsequently formed distal cusps in the maxillary molar. Though the sex identification accuracy for cusp diameters of the permanent maxillary first molar in Indians is relatively moderate (~61%), it can be used as an adjunct for sexing of adult Indians in forensic contexts. PMID- 26681854 TI - Detection of antimicrobial activity of banana peel (Musa paradisiaca L.) on Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: An in vitro study. AB - INTRODUCTION AND AIM: Banana is used widely because of its nutritional values. In past, there are studies that show banana plant parts, and their fruits can be used to treat the human diseases. Banana peel is a part of banana fruit that also has the antibacterial activity against microorganisms but has not been studied extensively. Since, there are no studies that relate the antibacterial activity of banana peel against periodontal pathogens. Hence, the aim of this study is to determine the antimicrobial activity of banana peel extract on Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans). MATERIAL AND METHODS: Standard strains of P. gingivalis and A. actinomycetemcomitans were used in this study which was obtained from the in-house bacterial bank of Department of Molecular Biology and Immunology at Maratha Mandal's Nathajirao G. Halgekar Institute of Dental Sciences and Research Centre. The banana peel extract was prepared, and the antibacterial activity was assessed using well agar diffusion method and minimum inhibitory concentration was assessed using serial broth dilution method. RESULTS: In the current study, both the tested microorganisms showed antibacterial activity. In well diffusion method, P. gingivalis and A. actinomycetemcomitans showed 15 mm and 12 mm inhibition zone against an alcoholic extract of banana peel, respectively. In serial broth dilution method P. gingivalis and A. actinomycetemcomitans were sensitive until 31.25 MUg/ml dilutions. CONCLUSION: From results of the study, it is suggested that an alcoholic extract of banana peel has antimicrobial activity against P. gingivalis and A. actinomycetemcomitans. PMID- 26681855 TI - A clinicomicrobiological study to evaluate the efficacy of manual and powered toothbrushes among autistic patients. AB - AIM: To compare the efficacy of powered toothbrushes in improving gingival health and reducing salivary red complex counts as compared to manual toothbrushes, among autistic individuals. MATERIALS AND METHODS: Forty autistics was selected. Test group received powered toothbrushes, and control group received manual toothbrushes. Plaque index and gingival index were recorded. Unstimulated saliva was collected for analysis of red complex organisms using polymerase chain reaction. RESULTS: A statistically significant reduction in the plaque scores was seen over a period of 12 weeks in both the groups (P < 0.001 for tests and P = 0.002 for controls). This reduction was statistically more significant in the test group (P = 0.024). A statistically significant reduction in the gingival scores was seen over a period of 12 weeks in both the groups (P < 0.001 for tests and P = 0.001 for controls). This reduction was statistically more significant in the test group (P = 0.042). No statistically significant reduction in the detection rate of red complex organisms were seen at 4 weeks in both the groups. CONCLUSION: Powered toothbrushes result in a significant overall improvement in gingival health when constant reinforcement of oral hygiene instructions is given. PMID- 26681856 TI - Efficacy of chlorhexidine and green tea mouthwashes in the management of dental plaque-induced gingivitis: A comparative clinical study. AB - BACKGROUND: The intake of green tea has been increased recently due to its medicinal values. The antibacterial and antioxidant properties of green tea were found to be beneficial in the treatment of gingival and periodontal diseases. The aim of this comparative study was to compare the efficacy of the mouthwash containing green tea and chlorhexidine in the management of dental plaque-induced gingivitis. MATERIALS AND METHODS: Thirty patients who participated in the study were divided randomly into two groups, each group of 15 patients was prescribed with either chlorhexidine or green tea mouthwash. Turesky modification of Quigley Hein plaque index, Loe and Silness gingival index, Ainamo and Bay bleeding index, tooth stain, and tongue stain (TS) were recorded at baseline, 15 days, and 1 month. The subjects were asked to report any discomfort or alteration in taste. RESULTS: There was a significant decrease in plaque index, gingival index, and bleeding index in both the groups. However, green tea mouthwash resulted in a statistically significant decrease in bleeding index compared to chlorhexidine group. There was no significant difference in tooth stain and TS in both the groups. CONCLUSION: The green tea-containing mouthwash is equally effective in reducing the gingival inflammation and plaque to chlorhexidine. PMID- 26681857 TI - Platelet concentration in platelet concentrates and periodontal regeneration unscrambling the ambiguity. AB - CONTEXT: Platelet-rich-plasma (PRP) and Platelet-rich-fibrin (PRF) are extensively used autologous platelet concentrates in periodontal regeneration, and PRF has a better efficacy as compared to PRP. The rationale for this difference has often been attributed to the difference in the structure of the fibrin matrix. However, the effect of concentration of platelets on the regenerative potential of these concentrates is obscure. AIMS: The study was conducted to evaluate and compare, clinically and radiographically, the efficacy of PRF and PRP in the treatment of periodontal endosseous defects and to assess the effect of platelet concentration on periodontal regeneration. MATERIALS AND METHODS: Twenty intrabony defects were selected and divided into two groups randomly by the coin toss method. Group I received PRP and Group II subjects were treated with PRF. The platelet counts in PRP and PRF were analyzed. Clinical and radiological parameters were assessed at baseline and 3, 6, and 9 months postoperatively. STATISTICAL ANALYSIS: Kruskal-Wallis Chi-square test, Wilcoxon signed rank test, t-test, and Spearman's rank correlation were used for statistical analysis of data. RESULTS: There was statistically significant improvement in all the parameters in the two groups except in relation to gingival recession. There was a statistically significant difference between the platelet count in Group I and Group II (P = 0.002). CONCLUSION: PRP and PRF appear to have nearly comparable effects in terms of periodontal regeneration. The concentration of platelets appears to play a paradoxical role in regeneration. The regenerative potential of platelets appears to be optimal within a limited range. PMID- 26681858 TI - Comparative scanning electron microscopy evaluation of Canal Brushing technique, sonic activation, and master apical file for the removal of triple antibiotic paste from root canal (in vitro study). AB - AIMS: To compare and evaluate the effectiveness of Canal Brushing technique, sonic activation, and master apical file (MAF) for the removal of triple antibiotic paste (TAP) from root canal using scanning electron microscopy (SEM). MATERIALS AND METHODS: Twenty-two single rooted teeth were instrumented with ProTaper up to the size number F2 and dressed with TAP. TAP was removed with Canal Brush technique (Group I, n: 6), sonic (EndoActivator) (Group II, n: 6), and MAF (Group III, n: 6). Four teeth served as positive (n: 2) and negative (n: 2) controls. The roots were split in the buccolingual direction and prepared for SEM examination (*1000) at coronal, middle, and apical third. Three examiners evaluated the wall cleanliness. STATISTICAL ANALYSIS: Statistical analysis was performed by Kruskal-Wallis test and Wilcoxon rank sum test. RESULTS: Difference in cleanliness between three groups is statistically significant in cervical region only. Pairwise comparison in cervical region Canal Brush and sonic activation showed more removal of TAP than MAF. CONCLUSIONS: Canal Brush and sonic activation system showed better result than MAF in the cervical and middle third of canal. In the apical third, none of the techniques showed a better result. None of the techniques showed complete removal of TAP from the canal. PMID- 26681859 TI - Odontogenic myxoma: Report of three cases and retrospective review of literature in Indian population. AB - PURPOSE: To review the clinical pattern and treatment modalities meted out to patients of odontogenic myxoma (OM) in Indian population in last 30 years and also to report 3 cases of OM. METHOD: A retrospective review of radiograph and histopathology of three cases of odontogenic myxoma treated between 2005 and 2011 was done. Immunohistochemical analysis was performed to examine the pattern of vimentin and NSE. Also a computerized literature search using Medline and Google scholar was conducted for published articles on OM in Indian population in last 30 years. RESULT: A total of 32 OM cases reviewed from 25 articles retrieved. Out of them 24 myxomas were present in maxilla, only 8 were in mandible and a single case was present in supraglottic region (larynx). Surgical procedure carried out was excision and curettage in 16 patients and resection with safe margin followed by reconstruction 13 patients. All the three reported cases were successfully treated by tumor enucleation and peripheral ostectomy with no recurrence after 3 to 7 years. CONCLUSION: Odontogenic myxoma is a rare odontogenic tumor with inconclusive clinical and radiographic features, hence histopathological examination is mandatory to confirm its diagnosis. Although the immunohistochemical analysis may help in diagnosis but plays no role in guiding treatment planning or predicting the rate of recurrence. Currently we lack data on number of reported OM cases in Indian population as author feels more patients must have been treated then reported. PMID- 26681860 TI - Evaluation of cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma cell-25 cell lines by 3-(4,5-dimethylthiazol-2-Yl) -2,5 diphenyltetrazolium bromide assay and determination of percentage of cell inhibition at G2M phase of cell cycle by flow cytometry: An in vitro study. AB - INTRODUCTION: Malignancies constitute a wide variety of disorders having high mortality and morbidity rates. Current protocols for management include surgical intervention, chemotherapy, and radiation which possess numerous adverse effects. Many phytochemicals are available with anticancer properties similar to anticancer drugs. Major benefit of these compounds is apparent lack of toxicity to normal tissues. Graviola (botanical name: Annona Muricata) contain bioactive compound "annonaceous acetogenins" known for anticancer activity on cancer cell lines. AIMS: To determine cytotoxicity of Graviola and percentage cell inhibition at G2M phase of cell cycle. SETTINGS AND DESIGN: The cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma (SCC-25) cell lines at various concentrations evaluated using 3-(4,5-dimethylthiazol-2-Yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The percentage of SCC-25 cell inhibition at G2M phase of cell cycle determined using flow cytometry. METHODS: Graviola Leaves, American Type Culture Collection SCC-25 cell lines were procured from Skanda Laboratories, Bengaluru. The cytotoxicity of aqueous extract of Graviola on SCC-25 cells at various concentrations evaluated using MTT assay. The percentage of SCC-25 cell inhibition at G2M phase of cell cycle determined using flow cytometry. STATISTICAL ANALYSIS: Statistical analysis was done using one-way ANOVA. RESULTS: MTT assay showed statistically significant (P < 0.001) dose dependent inhibition of SCC-25 cell lines by Graviola with IC50 value of 12.42 MUg/ml. Flow cytometry revealed that Graviola at 25 and 50 g/ml arrested 53.39% and 52.09% cells in G2M phase of cell cycle respectively, which was statistically significant. CONCLUSION: Graviola showed significant cytotoxic activity and percentage of cell inhibition at G2M phase cell cycle against SCC-25 cell lines. PMID- 26681861 TI - Evaluation of antimicrobial action of Carie CareTM and Papacarie DuoTM on Aggregatibacter actinomycetemcomitans a major periodontal pathogen using polymerase chain reaction. AB - BACKGROUND: In the present scenario, we are made available with chemomechanical caries removal system containing a natural proteolytic enzyme for the ease in the excavation of infected dentine. The additive action for these agents is providing antimicrobial and anti-inflammatory properties. AIM: This study was undertaken for assessing the action of Carie CareTM and Papacarie DuoTM on Aggregatibacter actinomycetemcomitans. MATERIALS AND METHODS: The samples were collected for cultivation of the periodontal pathogen from the clinical periodontal pockets using sterile paper points. The samples cultured under suitable conditions were analyzed with quantitative polymerase chain reaction targeting 16s r-DNA. The samples were divided into three groups namely, Group A: Control, Group B: With Papacarie Duo, Group C: With Carie Care. The pathogen inoculums plugs were inserted in the petri dishes containing chemically defined medium and the experimental gels at different concentrations and were incubated under optimal conditions. The inhibition of growth of the pathogen was studied visually. RESULTS: There was visual inhibition of growth for Group B and C and also exhibited a dose-dependent effect also. CONCLUSION: Based on the results of the present study, Carie CareTM gel demonstrated better antimicrobial action against A. actinomycetemcomitans which is a major periodontal disease causing pathogen. PMID- 26681862 TI - Faciomaxillary fractures in a Semi-urban South Indian Teaching Hospital: A retrospective analysis of 638 cases. AB - BACKGROUND AND OBJECTIVE: The incidence of maxillofacial trauma is increasing at a very fast pace in developing countries like India and poses a major health burden. Hence, the epidemiological data of maxillofacial trauma during a 6 year period, was analyzed to study the characteristics, factors predisposing, and aid in advocating strict guidelines to prevent the same. MATERIALS AND METHODS: Data related to 638 cases with maxillofacial trauma, from January 2008 to December 2014 were reviewed retrospectively and the data regarding gender, age, etiology, anatomic location of fracture, alcohol consumption, associated head and other injuries, modality of treatment rendered and associated complications were analyzed with descriptive statistics. RESULTS: A total of 638 patients presenting with 869 maxillofacial fractures were analyzed. Most of them [344 (53.9%)] were young adults aged 18-40, whereas, 123 (19.2%) were 11 to 17 years, and 97(15.2%) adults. Men (79.4%) were more affected than women. Road traffic accidents remain the main etiology causing fractures in 470 (73.6%), whereas 397 (62.2%) had history of consumption of alcohol. Those with alcohol intoxication had multiple injuries. Mandible was more frequently involved with 360 (41.4%) fractures, and condyle being the most common site. A total of 374 (58.6%) underwent open reduction with internal fixation under general anesthesia. Prevalence of other injuries was noted in 207 (32.4%) and complications of fracture treatment in 41(6.4%) cases. CONCLUSION: Road traffic accidents under alcohol influence were most commonly associated with comminuted facial fractures with head injuries, frequently leading to death. Mandible was the most commonly fractured facial bone followed by zygoma. PMID- 26681863 TI - Endodontic management of bilateral mandibular canine with type two canals configuration. AB - Successful endodontic treatment depends upon the clinician's knowledge and ability to manage aberrant anatomy. The mandibular canine normally comprises one canal and one root but 15% may have two canals with one or two foramina and even less frequent may have two roots. This paper presents a case report of bilateral mandibular canine having two root canals which merge into one canal and one foramina. PMID- 26681864 TI - Oral gingival myiasis: A rare case report and literature review. AB - Myiasis is a universal term for extreme infection by the parasitic fly larvae that feed on their host living/dead tissue. Gingival myiasis is a rare disease in the humans associated with poor oral hygiene, suppurative oral lesions, alcoholism, and senility, among other conditions. We present a case of gingival myiasis in the maxillary anterior region on the palatal surface in a 21-year-old mentally challenged male with moderate periodontitis and neurologic deficit. The diagnosis was made on the presence of larvae in the lesion. Treatment done was a manual removal of the larvae, one by one, with the help of the clinical forceps, surgical debridement of the oral wound, and subsequent management of the periodontal disease. PMID- 26681865 TI - Oral manifestations of secondary hyperparathyroidism: A case report. AB - There are a number of systemic diseases causing bony lesions throughout the body. Secondary hyperparathyroidism (HPT) which is associated with chronic renal failure is one such disorder resulting in a variety of bony changes. Secondary HPT develops when the parathyroid hormone is continuously produced in response to chronic low levels of serum calcium, a situation usually associated with the chronic renal disease. Here we present a case of secondary HPT causing bony changes in maxilla and mandible. PMID- 26681866 TI - Clinical enigma: A rare case of clear cell odontogenic carcinoma. AB - Clear cell odontogenic carcinoma is a rare, aggressive neoplasm of the jaw with only 74 reported cases. It occurs predominantly in the mandibular anterior region during fifth to seventh decades of life. Clinically it manifests as intra-bony swelling with a variable degree of pain. Microscopically, it reveals nests of cells with clear cytoplasm in connective tissue stroma arranged in different patterns. It is often misdiagnosed due to the rarity of lesion and confusing histopathology. Immunohistochemical staining plays an intricate role to uncertain the native of the clear cell to reach a confirmative diagnosis. The article aims to highlight the clinicopathologic features of clear cell odontogenic carcinoma in a middle-aged man with special emphasis on its differential diagnosis. PMID- 26681867 TI - A case of peripheral ameloblastoma of retromolar trigone: Histopathological and immunohistochemical profile. AB - Peripheral ameloblastoma (PA) is a rare and unusual entity with histological characteristics similar to those of the common intraosseous ameloblastoma. In this paper, we present a case of PA in a 44-year-old male affecting the right retromolar trigone area along with its immunohistochemical profile using CK19 and Ber-EP4 markers. PMID- 26681868 TI - Presurgical nasoalveolar molding in unilateral cleft lip and palate. AB - Unilateral cleft lip and palate (UCLP) patients have an esthetic and functional compromise of the middle third of the face and nasal structures. To improve the esthetic result of lip repair, the concept of presurgical nasoalveolar molding (PNAM) was brought into conception. PNAM is an easy and passive method of bringing the alveolus and lips together by redirecting the forces of natural growth. This case report documents a 2-year follow-up of PNAM in UCLP. PMID- 26681869 TI - Surgical re-entry evaluation of regenerative efficacy of bioactive Gengigel((r)) and platelet-rich fibrin in the treatment of grade II furcation: A novel approach. AB - The furcation area creates situations in which routine periodontal procedures are somewhat limited, and surgical procedures are generally required. The introduction of bioactive agents, such as platelet concentrates, enamel matrix derivatives, bone morphogenic proteins, and matrix macromolecules such as hyaluronic acid has expanded the scope for better outcomes in furcation treatment. Hyaluronic acid is a naturally occurring nonsulfated high molecular weight glycosaminoglycan that forms a critical component of the extracellular matrix and contributes significantly to tissue hydrodynamics, cell migration, and proliferation. Platelet-rich fibrin (PRF) is an immune and platelet concentrate containing all the constituents of a blood sample, which are favorable for healing and immunity. The purpose of the present case report was to assess through surgical re-entry, the regenerative capacity of Gengigel((r)) in conjunction with PRF in a patient with grade II furcation defect. It was observed that the combined approach resulted in significant furcation defect fill on re evaluation at 6 months. PMID- 26681870 TI - Revitalization of traumatized immature tooth with platelet-rich fibrin. AB - Endodontic treatment options for immature, nonvital teeth conventionally include surgical endodontics, apexification with calcium hydroxide, or single visit mineral trioxide aggregate plug. Regeneration is a new concept which is been introduced in the treatment of traumatized open apex tooth. Regeneration of pulp dentin complex in an infected necrotic tooth with an open apex is possible if the canal is effectively disinfected. The purpose of this case report is to add a new vista in regenerative, endodontic therapy by using platelet-rich fibrin for revitalization of immature nonvital tooth. PMID- 26681871 TI - Oral epithelioid hemangioendothelioma. AB - Epithelioid hemangioendothelioma (HE) is an intermediate malignant potential vascular neoplasm with uncertain clinical behavior, wide variations in microscopic findings, and prognosis. According to the World Health Organization (2002) classification, epithelioid HE has been considered under malignant tumors which rarely metastasize. The epithelioid variant, the most aggressive one, has similar gender predilection and sporadic occurrence in children. The patients usually present with an asymptomatic oral mass whereas few cases may report with the painful bleeding lesion. We attempt to present a case in an adolescent male with previously never described biological behavior, diverse histopathological features, and immunohistochemistry findings. PMID- 26681872 TI - Psammomatoid variant of juvenile ossifying fibroma involving mandible: A rare case report. AB - The term juvenile ossifying fibroma (JOF) is used in literature in naming two microscopically distinct fibro-osseous lesions of the craniofacial skeleton. One is characterized by small uniform spherical ossicles resembling psammoma bodies (psammomatoid JOF [PsJOF]). The other is distinguished by trabeculae of fibrillary osteoid and woven bone (trabecular JOF). Psammomatoid ossifying fibromas represent a unique subset of fibro-osseous lesions of the craniofacial region. PsJOF has been distinguished because of its location, clinical behavior, and age of occurrence. They have distinctive histomorphologic features and a tendency toward locally aggressive behavior, including invasion and destruction of adjacent anatomic structures. It is generally seen in the younger age group, and the most common site is paranasal sinuses, orbits, and frontoethmoidal complex. We report a case of JPOF involving mandible which is rarely been described in literature. An insight into the radiographic progression of this rare entity along with the clinical feature and surgical management is discussed. PMID- 26681874 TI - National Seminar on "Regulatory and Quality Aspects of Herbal Drugs and Botanicals". PMID- 26681873 TI - Oral lymphangioma: A rare case report. AB - Lymphangiomas are benign hamartomatous tumors of the lymphatic channels which present as developmental malformations arising from sequestration of lymphatic tissue that do not communicate with the rest of the lymphatic channels. Lymphatic vessels are filled with a clear protein-rich fluid containing few lymph cells. It can also occur in association with hemangioma. The onset of lymphangiomas are either at birth (60% to 70%) or up to two years of age (90%) and rare in adults. Lymphangiomas have marked predilection for the head and neck region (50-70%). The most common location in the mouth is the dorsum of tongue, followed by lips, buccal mucosa, soft palate, and floor of the mouth. On tongue, they may present as a localized or a diffused growth which may enlarge to cause macroglossia, impaired speech and difficulty in mastication. Herewith, we present a rare case of lymphangioma of tongue leading to macroglossia in a 8-year-old boy. PMID- 26681875 TI - Hepatoprotective activity of a new polyherbal formulation against paracetamol and D-galactosamine induced hepatic toxicity. AB - OBJECTIVE: The present study was envisaged to evaluate the protective effect of polyherbal formulation, DRDC/AY/8060, developed by Dabur India Ltd., against paracetamol and D-galactosamine induced hepatic toxicities in Wistar rats. MATERIALS AND METHODS: The study was carried out in two different experiments of 10 and 14 days against paracetamol and D-galactosamine, respectively. Animals were divided into different treatment groups (n = 6). The control group received normal saline, a toxicant group in two experiments received paracetamol 750 mg/kg p.o. every 72 h for 10 days and D-galactosamine 400 mg/kg i.p. single dose. The test formulation was used at the two dose levels of 120 and 240 mg/kg/day. Treatment groups treated with test formulations were also administered D galactosamine as given in toxicant group. At the end of the dosing schedule, blood was withdrawn from the retrobulbar plexus of the animals for serum estimation of serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate trasnferase (SGPT), albumin, bilirubin, and alkaline phosphatase (ALP). Following the withdrawal of blood animals was sacrificed, and liver tissue was excised for estimation of thiobarbituric acid reactive substances (lipid peroxidation, malondialdehyde), tissue glutathione (GSH) and histopathological studies. RESULTS: It was evident from the biochemical estimation that both paracetamol and galactosamine caused hepatotoxicity in the toxicant groups. However, treatment with DRDC/AY/8060 significantly (P < 0.001, vs. toxicant) reduced the levels of SGOT, SGPT, serum bilirubin, and ALP, as well as decreased lipid peroxidation. In addition, treatment with test formulation also significantly (P < 0.001, vs. toxicant) elevated serum albumin and GSH levels compared to toxicant groups. CONCLUSION: On the basis of these studies and comparative evaluation it can be concluded that the formulation DRDC/AY/8060 showed hepatoprotective activity against paracetamol and D-galactosamine at 120 mg/kg and 240 mg/kg. PMID- 26681876 TI - Development of standard operating procedure and standardization of Habb-e Banafsha Qawi-A Unani polyherbal formulation. AB - INTRODUCTION: Herbals drugs became a boon for mankind since ancient times and still are used worldwide for the treatment of various human ailments. The safety of alternative medicinal preparations has been questioned due to reports of unwanted side effects. To maintain the quality and efficacy of these drugs, it is essential to standardize them in order to avoid the use of substandard or adulterated medicines in the market. Unani system of medicine mainly focuses on the treatment by natural drugs. Habb-e-Banafsha Qawi is useful in a cough, catarrah, and coryza. MATERIALS AND METHODS: Physiochemical constants of Habb-e Banafsha Qawi were determined through organoleptic characters, macro- and micro scopic characters, ash value, solubility, pH values. Chromatographic fingerprints were developed using thin layer chromatography method. Aflatoxin (AF) contamination, heavy metal, and pesticide residues were also evaluated by standard methods. OBJECTIVES: In the present study, an attempt has been made to develop standard operating procedure and physiochemical parameters to monitor the quality of a Unani poly-herbal formulation, Habb-e-Banafsha Qawi. RESULTS: The tablets tasted sweetish bitter with a pleasant odor, water soluble and acidic in nature. R f values were almost same in all the extracts. No AF, heavy metal, and pesticide residues were observed. CONCLUSIONS: It may be concluded that the values and chromatographic fingerprints obtained can be used for quality evaluation and to set new pharmacopoeial standards for the preparation of Habb-e Banafsha Qawi. PMID- 26681877 TI - Quality control aspects of herbs and botanicals in developing countries: Coleus forskohlii Briq a case study. AB - OBJECTIVE: Current trend of commercialization of herbal medicines draw a huge need of maintaining their quality. The declaration of quality, safety and efficacy of medicinal plants as well as poly-herbal formulations has become an important issue. Hence, qualitative and quantitative analysis of herbal drugs and formulations viz., fingerprint profiles and quantification of the various markers become key factors of quality control. MATERIALS AND METHODS: Present investigation is a detailed report for quality control of well-known herb Coleus forskohlii Briq, which includes physicochemical parameter determination, safety evaluation, microscropical evaluation, and chromatographic fingerprinting as well. RESULTS: Physico-chemical characters were evaluated according to Indian Pharmacopoeia, further microscopic evaluation of transverse section of Coleus reveals that periderm, secondary phloem, and wide secondary xylem cylinder, which occupies major portion of the root fragmentary. Chromatographic fingerprint profiles of Coleus have been generated, and a marker based standardization strategy was adopted; using different analytical technique like high-performance thin layer chromatography, high-performance liquid chromatography and gas chromatography-mass spectroscopy to maintain quality and ensure safety as well as efficacy. CONCLUSION: These advancements in modern techniques of analysis can lead to effective quality control of Coleus as well as other herbs. Present report can act as pioneer for quality control of modern herbal medicine. PMID- 26681878 TI - A high performance thin layer chromatographic method for the estimation of colchicine in different formulations. AB - BACKGROUND: Colchicine is a main alkaloid present in bitter and sweet variety of colchicum (Colchicum luteum Baker), which have been reported to possess anti rheumatic, anti-gout, and anticancer potential. Colchicum is an important ingredient of several Unani and Herbal formulations. Quantification of colchicine will play a great role in quality control of these formulations. Hence, a high performance thin layer chromatographic (TLC) method has been developed for the analysis of colchicine in Unani formulations of various dosage forms such as hubb (tablet) and capsules. MATERIALS AND METHODS: The samples were applied on aluminum TLC plates precoated with silica gel 60-F254 and developed using mobile phase toluene-dichloromethane-methanol in equal proportions. Quantification was done by densitometric scanning at 350 nm, which showed a linear response in the range of 50-500 ng/spot. The developed method was validated as per the International Conference on Harmonization guidelines for linearity, precision, accuracy, specificity, robustness, limit of detection, and limit of quantification. RESULTS AND CONCLUSION: The developed method was applied for quantitative estimation of colchicine in different Unani and Herbal formulations. The method was found simple, selective, accurate with a wide range of linearity, hence suitable for the quality control of different formulations and varieties of colchicum with respect to colchicine content. PMID- 26681879 TI - Determination of nucleosides in Cordyceps sinensis and Ganoderma lucidum by high performance liquid chromatography method. AB - BACKGROUND: Nucleosides are supportive in the regulation and modulation of various physiological processes in body, they acts as precursors in nucleic acid synthesis, enhance immune response, help in absorption of iron and influence the metabolism of fatty acids. Cordyceps sinensis and Ganoderma lucidum are well known for its use in traditional medicine of China, Nepal and India. They are rich in nucleosides such as adenine, adenosine, cordycepin, etc. Hence, a simple, economic and accurate high-performance liquid chromatography (HPLC) analytical method was proposed for determination of adenine and adenosine for the quality control of plants. MATERIALS AND METHODS: Chromatographic experiments were conducted on YL9100 HPLC system (South Korea). Reversed-phase chromatography was performed on a C18 column with methanol and dihydrogen phosphate as the mobile phase in isocratic elution method at a flow rate of 1.0 mL/min. Detection was carried out at 254 nm, which gives a sharp peak of adenine and adenosine at a retention time of 6.53 +/- 0.02 min and 12.41 +/- 0.02, respectively. RESULTS AND DISCUSSION: Linear regression analysis data for the calibration plot showed a good linear relationship between response and concentration in the range of 25 200 ug/mL for adenosine and 100-800 ug/mL for adenine with regression coefficient of 0.999 and 0.996, respectively. The adenine was found 0.16% and 0.71% w/w in G. lucidum and in C. sinensis, respectively, and adenosine was found to be 0.14% w/w in G. lucidum whereas absent in C. sinensis. CONCLUSION: The developed HPLC method for the quantification of adenosine and adenine can be used for the quality control and standardization of crude drug and for the different herbal formulations, in which adenine and adenosine are present as major constituents. The wide linearity range, sensitivity, accuracy, and simple mobile phase imply the method is suitable for routine quantification of adenosine and adenine with high precision and accuracy. PMID- 26681881 TI - Bergenin determination in different extracts by high-performance thin-layer chromatographic densitometry. AB - AIM: Bergenin is an active secondary metabolite, found in Bergenia ligulata, family Saxifragaceae, which is an important medicinal plant used in the traditional system of medicine. It is distributed throughout the South and East Asia and some European countries, usually growing on high altitude in the Himalayan region and known as Pashanbhed (meaning "to break the stone"). The rhizome of B. ligulata has been used since long time in different traditional formulations of kidney and liver disorders. Due to its exhaustive use in the traditional system, it is commonly adulterated with the rhizome of other plants which do not contain its chemical marker bergenin. Hence, we developed high performance thin-layer chromatographic (HPTLC) method for quantification of bergenin in B. ligulata which can be used for its quality control. MATERIALS AND METHODS: A sensitive HPTLC method has been developed for the estimation of bergenin in different extracts of B. ligulata and its traditional formulations. Precoated HPTLC silica gel plates were used as stationary phase, and chloroform: methanol: acetic acid (8:1:1, v/v/v) was used as mobile phase. RESULTS: The Rf value of bergenin was found to be 0.28 +/- 0.03. Detection and quantification were performed by densitometry at 276 nm. The calibration plot was linear in the range of 200-5000 ng of bergenin with the correlation coefficient of (r (2)) 0.999, which confirms good linearity. The content of bergenin in methanolic and acetone extracts was found to be 5.51 +/- 0.14 and 5.76 +/- 0.16, respectively. CONCLUSION: The method can be applied for quality control and standardization of B. ligulata and its traditional formulations as well as for checking the presence of adulterants. PMID- 26681880 TI - Chromatographic analysis of wheatgrass extracts. AB - AIM: Wheatgrass (WG) is the shoot of Triticum aestivum Linn. belongs to the family Gramineae, and possess high chlorophyll content and essential vitamins, minerals, vital enzymes, amino acids, dietary fibers etc., It has been shown to possess anti-cancer, anti-ulcer, antioxidant, and anti-arthritic activity due to the presence of biologically active compounds, and minerals. Therefore, in the present study, high-performance thin layer chromatography (HPTLC), and high performance liquid chromatography (HPLC) methods for qualitative and quantitative analysis have been proposed, which will help in quality evaluation of wheat grass extract. MATERIALS AND METHODS: Samples for analysis were prepared in methanol and water simply by sonication. These were applied on pre-coated silica plate and chromatograms were developed using toluene: Ethyl acetate: Formic acid. HPLC analysis was done on Waters HPLC system using water, methanol, and acetonitrile as mobile phase. Merck C18 column has been used. RESULTS: HPTLC finger printing of alcoholic extracts of WG was carried out and found 10-11 spots at different wavelengths 254, 366, and 435 nm. HPLC fingerprinting produced 22 peaks at 256 nm. Quantitative HPTLC analysis was done to determine the gallic acid content, and was found to be 0.077% w/w in aqueous extract. By HPLC, the content of gallic acid and rutin was found to be 0.07%, and 0.04% w/w in aqueous extract of WG. CONCLUSION: The developed HPLC and HPTLC fingerprinting method can be used for the quality control, and standardization of WG and its extracts used as nutritional supplement. PMID- 26681882 TI - Standardization and in vitro antioxidant activity of jatamansi rhizome. AB - BACKGROUND: Nardostachys jatamansi Linn. commonly known as jatamansi is a well notorious drug in Indian systems of medicines having various health-related benefits and employed in various herbal formulations due to the presence of high levels of valuable phenolic constituents. The present study was aimed to quality assessment of Jatamansi rhizome by studying macro- and micro-scopic characters along with physicochemical tests, chemo-profiling using thin layer chromatography (TLC), and gas chromatography-mass spectrometry (GC-MS), in vitro antioxidant activity. MATERIALS AND METHODS: Standardization was carried out as per the pharmacopeial guidelines and contaminant estimation was carried out by analyzing the samples for the determination of heavy metals, pesticides, and aflatoxins. Chemo-profiling was done with TLC by optimizing the mobile phase for different extracts. The GC-MS chemo-profiling was also carried out by using hexane soluble fraction of the hydroalcoholic extract. The drug is well known for a protective role in the human body as an antioxidant, so total phenolic contents and in vitro antioxidant efficacy was also determined by using established methods. RESULTS: The results of quality control and anatomical studies were very much useful for its identification, whereas significant antioxidant efficacy was also observed. The drug was found free of contaminants when analyzed for pesticides and aflatoxins, whereas heavy metals were found under the pharmacopeial limit. CONCLUSION: The findings of the present research can be utilized for the identification and quality control of the jatamansi rhizome. PMID- 26681884 TI - Characterization of Linum usitatissimum L. oil obtained from different extraction technique and in vitro antioxidant potential of supercritical fluid extract. AB - AIM: Present investigation was aimed to characterize the fixed oil of Linum usitatissimum L. using five different extraction methods: Supercritical fluid extraction (SFE), ultrasound-assistance, soxhlet extraction, solvent extraction, and three phase partitioning method. MATERIALS AND METHODS: The SFE conditions (temperature, pressure, and volume of CO2) were optimized prior for better yield. The extracted oils were analyzed and compared for their physiochemical parameters, high performance thin layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), and Fourier-transformed infrared spectroscopy (FT-IR) fingerprinting. Antioxidant activity was also determined using 1,1-diphenyl-2-picrylhydrazyl and superoxide scavenging method. RESULT: The main fatty acids were alpha-linolenic acid, linoleic acid, palmitic acid, and stearic acid as obtained by GC-MS. HPTLC analysis revealed the presence of similar major components in chromatograms. Similarly, the pattern of peaks, as obtained in FT-IR and GC-MS spectra of same oils by different extraction methods, were superimposable. CONCLUSION: Analysis reported that the fixed oil of L. usitatissimum L. is a good source of n-3 fatty acid with the significant antioxidant activity of oil obtained from SFE extraction method. PMID- 26681883 TI - Quality control and in vitro antioxidant potential of Coriandrum sativum Linn. AB - BACKGROUND: Coriandrum sativum Linn., commonly known as coriander, is a well known spice and drug in India. It has various health-related benefits and used in various Unani formulations. In this present study, quality assessment of coriander fruits was carried out by studying anatomical characters, physicochemical tests, and chemoprofiling using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectroscopy (GC-MS) along with in vitro antioxidant potential. MATERIALS AND METHODS: Standardization was carried out as per the pharmacopeial guidelines. Estimation of heavy metals, pesticides, and aflatoxins was carried out to ascertain the presence of any contaminant in the sample. Chemoprofiling was achieved by thin layer chromatography (TLC) by optimizing the mobile phase for different extracts. The most of the pharmacological activities of coriander are based on volatile oil constituents. Hence, GC-MS profiling was also carried out using hexane-soluble fraction of hydro-alcoholic extract. The total phenolic contents and in vitro antioxidant efficacy were determined using previously established methods. RESULTS: The quality control and anatomical studies were very valuable for the identification whereas good antioxidant potential was observed when compared to ascorbic acid. The drug was found free of contaminant when analyzed for pesticides and aflatoxins whereas heavy metals were found under reported limits. CONCLUSION: The work embodied in this present research can be utilized for the identification and the quality control of the coriander fruit. PMID- 26681885 TI - Antidiabetic activity of ethanolic extract of Cyperus rotundus rhizomes in streptozotocin-induced diabetic mice. AB - OBJECTIVE: In the present investigation, ethanolic extract of Cyperus rotundus (EECR) rhizomes was evaluated for antidiabetic activity in streptozotocin (STZ) induced diabetic swiss mice. MATERIALS AND METHODS: After administration of EECR extract for 3 weeks, the body weight, blood glucose, biomarker enzymes (serum glutamic pyruvic transaminase [SGPT] and serum glutamic oxaloacetic transaminase [SGOT]), and plasma lipid levels were measured in STZ-induced diabetic mice. RESULTS: The ethanolic extract at dose levels of 250 and 500 mg/kg body weight revealed significant antidiabetic activity, improvement in body weight, and reduction in elevated biochemical parameters such as SGPT, SGOT, cholesterol, and triglyceride levels. CONCLUSION: These experimental findings seemed to indicate the use of this plant in traditional Indian medicine for the treatment of diabetes. PMID- 26681886 TI - Current status of herbal product: Regulatory overview. AB - A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment. PMID- 26681887 TI - Hepatoprotective potential of kumaryasava and its concentrate against CCl4 induced hepatic toxicity in Wistar rats. AB - OBJECTIVE: Kumaryasava (KS) is a marketed Ayurvedic formulation containing Aloe vera as the main ingredient. It has been used widely for the treatment of liver disorders; however, there is a lack of modern scientific data on hepatoprotection. The recommended dose of KS is high and up to 60 mL/day. The present study describes the preparation of new KS concentrate and evaluation of comparative hepatoprotective activity of KS and prepared KS concentrate at one third of KS dose against CCl4-induced hepatic toxicity. MATERIALS AND METHODS: Animals were divided into different groups (n = 6). The first group received normal saline (control) 1.0 mL/Kg/day p.o. for 10 days. The second group (toxicant) was given normal saline 1.0 mL/Kg/day p.o. for 10 days with CCl4 in olive oil (1:1 v/v) at 1.0 mL/Kg/day p.o. Third, fourth, and fifth groups received KS, KS concentrate and a marketed formulation as standard) at doses of 5.0 mL/Kg/day p.o., 1.6 mL/Kg/day p.o., and 100 mL/Kg/day p.o. (tablet suspended in water using 0.1% carboxymethyl cellulose) respectively for 10 days along with CCl4 as given to the toxicant group. On the 11(th) day, blood was withdrawn from retro-orbital plexus and serum was separated for biochemical estimation of serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), and albumin levels. Later, animals were sacrificed under high dose of anesthesia to remove liver tissue, which were removed and washed with ice cold saline for the estimation of lipid peroxidation. Liver tissue from each group was also fixed in 10% formalin for histopathological analysis. RESULTS: Results demonstrated that both KS and KS concentrate showed the protection against CCl4-induced hepatic toxicity. This was evident from the reduction in serum SGOT, SGPT, ALP levels, and elevation in serum albumin levels observed post treatment of CCl4 treated rats with KS and KS concentrate, which were supported by histopathological data. CONCLUSION: KS concentrate can be a useful hepatoprotective formulation which may help in reducing the high dose of KS to approximately one-third of the recommended dose. PMID- 26681888 TI - Antimicrobial activity of aqueous and organic extracts of a Saudi medicinal plant: Rumex nervosus. AB - OBJECTIVE: The antimicrobial effect of aerial part of Rumex nervosus obtained from the Southern region of Saudi Arabia was evaluated on bacterial strains Staphylococcus aureus, methicillin resistant S. aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas Aeruginosa, and fungal strain Candida albicans. MATERIALS AND METHODS: The solvents used for the extraction were aqueous, hexane, and methanol. The in vitro antimicrobial activity was performed by agar diffusion and disk diffusion methods and the confirmation of this activity was done by the enumeration of colony forming units (CFU). RESULTS: The aqueous extract showed the growth inhibitory effect on Gram-positive bacteria while the Gram-negative P. aeruginosa was the most sensitive microorganism as determined by the agar diffusion technique. Surprisingly, the extract showed little antibacterial activity on other Gram-negative bacteria (E. coli) by this technique. Ethanolic extract was also found to be inhibitory to the growth of microorganisms. Hexane extract was relatively low in antimicrobial activity on Gram-negative E. coli and P. aeruginosa, while both the organic extracts were inhibitory to the growth of the fungus, C. albicans. Hexane gave no conclusive results with agar or disk diffusion methods, but showed the microbial growth inhibition in CFU enumeration. The antibacterial activity of active extracts was compared with vancomycin while antifungal activity of was compared with amphotericin B. CONCLUSION: The results obtained in the present study suggest that R. nervosus showed a marked antimicrobial activity with the test organisms. PMID- 26681889 TI - Optimization of ultrasound-assisted extraction of charantin from Momordica charantia fruits using response surface methodology. AB - BACKGROUND: Momordica charantia Linn. (Cucurbitaceae) fruits are well known for their beneficial effects in diabetes that are often attributed to its bioactive component charantin. OBJECTIVE: The aim of the present study is to develop and optimize an efficient protocol for the extraction of charantin from M. charantia fruits. MATERIALS AND METHODS: Response surface methodology (RSM) was used for the optimization of ultrasound-assisted extraction (UAE) conditions. RSM was based on a three-level, three-variable Box-Behnken design (BBD), and the studied variables included solid to solvent ratio, extraction temperature, and extraction time. RESULTS: The optimal conditions predicted by the BBD were: UAE with methanol: Water (80:20, v/v) at 46 degrees C for 120 min with solid to solvent ratio of 1:26 w/v, under which the yield of charantin was 3.18 mg/g. Confirmation trials under slightly adjusted conditions yielded 3.12 +/- 0.14 mg/g of charantin on dry weight basis of fruits. The result of UAE was also compared with Soxhlet extraction method and UAE was found 2.74-fold more efficient than the Soxhlet extraction for extracting charantin. CONCLUSIONS: A facile UAE protocol for a high extraction yield of charantin was developed and validated. PMID- 26681890 TI - Development and validation of high-performance liquid chromatography and high performance thin-layer chromatography methods for the quantification of khellin in Ammi visnaga seed. AB - OBJECTIVE: The present study was used to design simple, accurate and sensitive reversed phase-high-performance liquid chromatography RP-HPLC and high performance thin-layer chromatography (HPTLC) methods for the development of quantification of khellin present in the seeds of Ammi visnaga. MATERIALS AND METHODS: RP-HPLC analysis was performed on a C18 column with methanol: Water (75: 25, v/v) as a mobile phase. The HPTLC method involved densitometric evaluation of khellin after resolving it on silica gel plate using ethyl acetate: Toluene: Formic acid (5.5:4.0:0.5, v/v/v) as a mobile phase. RESULTS: The developed HPLC and HPTLC methods were validated for precision (interday, intraday and intersystem), robustness and accuracy, limit of detection and limit of quantification. The relationship between the concentration of standard solutions and the peak response was linear in both HPLC and HPTLC methods with the concentration range of 10-80 MUg/mL in HPLC and 25-1,000 ng/spot in HPTLC for khellin. The % relative standard deviation values for method precision was found to be 0.63-1.97%, 0.62-2.05% in HPLC and HPTLC for khellin respectively. Accuracy of the method was checked by recovery studies conducted at three different concentration levels and the average percentage recovery was found to be 100.53% in HPLC and 100.08% in HPTLC for khellin. CONCLUSIONS: The developed HPLC and HPTLC methods for the quantification of khellin were found simple, precise, specific, sensitive and accurate which can be used for routine analysis and quality control of A. visnaga and several formulations containing it as an ingredient. PMID- 26681891 TI - Effect of detoxification (tadbeer) in content of toxic metabolites of Strychnos nux-vomica: A Unani approach for its use in human. AB - BACKGROUND: Azaraqi (Strychnos nux-vomica, Loganiaceae) has been the important Unani medicine since long time as a stimulant, anti-inflammatory, and blood purifier. It has been used very frequently by the Unani practitioner. But the Unani system recommends application of azaraqi in medicine only after its detoxification (tadbeer) may be because of the presence of its deadly poisonous alkaloids (strychnine and brucine). In the present investigation, an attempt has been made to quantify the actual content of their toxic alkaloids before and after the tadbeer. MATERIALS AND METHODS: A sensitive high-performance thin layer chromatographic (HPTLC) method has been developed for estimation of strychnine and brucine in different samples of azaraqi before and after tadbeer. Precoated HPTLC silica gel plates were used as stationary phase and (toluene: Ethyl acetate: Dietylamine 7:2:1 v/v/v) was used as mobile phase. RESULT: The Rf value of strychnine and brucine was found as 0.53 and 0.41, respectively. Detection and quantification were performed by densitometry at 270 nm. The calibration plot was linear in the range of 50-1000 ng of strychnine and brucine, respectively, with the correlation coefficient (r (2)) 0.993 and 0.991 for strychnine and brucine, respectively, which confirms good linearity. The content of strychnine was 0.175, 0.07, 0.18, 0.051, and 0.075% w/w whereas brucine was 0.16, 0.117, 0.061, 0.045, and 0.057 in crude azaraqi, azaraqi without outer cover, azaraqi outer cover only, azaraqi mudabbar and azaraqi mudabbar by fried in ghee, respectively. CONCLUSION: The detoxification results in sharp decrease in content of toxic metabolites. The process by boiling in milk was found much effective but tedious as compare to frying method. PMID- 26681892 TI - Effect of piperine on pharmacokinetics of sodium valproate in plasma samples of rats using gas chromatography-mass spectrometry method. AB - Piperine (PIP) is used as anticonvulsant in traditional Chinese medicine. Co administration of low-dose sodium valproate with PIP has been regarded to have potential anticonvulsant activity. AIM: This study was intended to investigate the effect of PIP on the pharmacokinetics of sodium valproate (SVP) in the plasma samples of rats using gas chromatography-mass spectrometry (GC-MS) method. MATERIALS AND METHODS: The plasma samples obtained after oral administration of SVP, 150 mg/kg and SVP, 150 mg/kg + PIP, and 5 mg/kg to male Wistar rats were used to quantify the concentrations in plasma using GC-MS method. RESULTS: A simple and accurate method developed in-house was applied for the analysis of plasma samples of Wistar rats after oral administration of SVP and PIP + sodium valproate, respectively. The pharmacokinetic parameters reported 14.8-fold increase in plasma concentration (maximum observed concentration in the concentration-time profile), 4.6-fold increase in area under the curve and slightly prolonged time to reach that concentration (1 h) of SVP in presence of PIP. CONCLUSION: The study reaffirms the bioenhancing effect of PIP suggesting possibility of dose reduction of SVP while co-adminstering with PIP. PMID- 26681893 TI - Stability studies of silymarin nanoemulsion containing Tween 80 as a surfactant. AB - BACKGROUND: Silymarin, a flavonolignan from "milk thistle" (Silybum marianum) plant is used almost exclusively for hepatoprotection. Because of its low bioavailability, it was incorporated into a nanoemulsion formulation. The aim of the present study was to check the stability of silymarin nanoemulsion at different temperatures for 3 months. MATERIALS AND METHODS: The oil-in-water based nanoemulsion formulation was prepared by titration method. Silymarin nanoemulsion was characterized by droplet size, viscosity, and refractive index. Droplet size, viscosity, and refractive index were determined every month. The shelf-life of silymarin nanoemulsion was determined by accelerated stability testing. RESULTS: It was found that there was no significant change in the droplet size, viscosity, and refractive index at refrigerator and room temperature during the period of 3 months. The half-life of the optimized nanoemulsion formulation was found to be 4.74 years at room temperature. CONCLUSION: These results indicated that stability of silymarin can be enhanced in nanoemulsion formulation using Tween 80 as a surfactant. PMID- 26681894 TI - Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line. AB - BACKGROUND: The ethanolic extract of Bacopa monnieri contains bacoside A and B, brahmin, cucurbitacins, and betulinic acid. Currently, cucurbitacins have also been reported for their strong anti-tumorigenic and anti-proliferative activity by inducing cell cycle arrest at the G2/M phase and formation of multiplied cells. The present study was carried out to evaluate the in vitro cytotoxic activity of ethanolic extract of dichloromethane (DCM) fraction of B. monnieri on two different cell lines. MATERIALS AND METHODS: The ethanolic extract of B. monnieri was prepared using soxhlet extraction method and different fractions (hexane, DCM, methanol, acetone, and water) of ethanolic extracts were prepared. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of ethanolic extract and of all fractions was carried out on MCF-7 and MDA-MB 231 cell lines. The presence of cucurbitacins and betulinic acid in these fractions was confirmed by high-performance thin layer chromatography. RESULTS: The IC50 values of ethanolic extract of B. monnieri in MCF-7 and MDA-MB 231 cell lines were 72.0 MUg/mL and 75.0 MUg/mL, respectively. The DCM fraction of B. monnieri showed maximum cytotoxic activity among all fraction upto 72 h and was found to be 57.0 MUg/mL and 42.0 MUg/mL, respectively. CONCLUSION: The results showed good cytotoxic activity in DCM fraction in both the cell lines may be due to the presence of cucurbitacins and betulinic acid in DCM fraction. PMID- 26681895 TI - Challenges and guidelines for clinical trial of herbal drugs. AB - World Health Organization (WHO) has defined herbal medicines as finished labeled medicinal product that contain an active ingredient, aerial, or underground parts of the plant or other plant material or combinations. According to a report of WHO, about 80% of the world population is reported to rely on traditional medicine for their primary health care needs. Even in the developed countries, complementary or alternative medicine is gaining popularity. A report of a global survey on national policy on traditional medicine and regulation of herbal medicines indicated that about 50 countries including China, Japan, and Germany already have their national policy and laws on regulations of traditional medicines. Herbal drugs possess a long history of its use and better patient tolerance. These are cheaper and easily available in countries like India due to rich agro culture conditions. However, reckless utilization of resources threatens the sustainability of several plant species. Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945. In 1959, the Government of India amended the Drugs and Cosmetics Act to include drugs that are derived from traditional Indian medicine. In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee directed that the procedures laid down by the office of the Drug Controller General of India for allopathic drugs should be followed for all traditional and herbal products to enter into clinical trials for any therapeutic condition. However, there are certain loop holes in the clinical trials of herbal drugs as the lack of stringent bylaws and regulations. Hence, a deep insight of important challenges and major regulatory guidelines for clinical trial of herbal drugs and botanicals is discussed in the present communication. There is lack of scientific evidence to evaluate safety and efficacy of herbal drugs. The quality of the trial drug has to be tested for batch-to-batch uniformity of the active constituents. It is very difficult to have active and control groups with identical color, smell and taste of the herbal drug, which cannot be imitated while manufacturing a placebo. These challenges can be reduced or overcome by applying most recent methodologies and guidelines for clinical trials. Since the quality control of herbal medicines is complicated and difficult, relevant and appropriate requirements should be established for the assessment of safety and efficacy for different categorized herbal medicines to reduce cost and expenditure. And, efforts should be made for the integration of traditional medicine into national healthcare systems. Different challenges and regulatory guidelines discussed for the clinical trial of herbal drugs will be useful for various industries for considering it before going ahead for clinical trial of their product. PMID- 26681896 TI - Theoretical calculation of a composite pulse for 2H broadband excitation by average Hamiltonian theory. AB - Quadrupolar echo NMR spectroscopy of solids often requires RF pulse excitation that covers spectral widths exceeding 100 kHz. In a recent work we found out that a four pulse, composite pulse COM-II ( [Formula: see text] ), provided robust broadband excitation for deuterium quadrupolar echo spectroscopy. Moreover, when combined with an eight step phase cycle, spectral distortions arising from finite pulse widths were greatly supressed. In this paper we report on a theoretical analysis COM-II with 8-step phase cycle by average Hamiltonian theory. This treatment is combined with the fictitious spin-1 operator formalism, and the mechanism of the 8-step phase cycling that minimizes the spectral distortions is discussed. PMID- 26681898 TI - A Clinical Reminder About The Safe Use of Insulin Vials. AB - A clinical reminder about the safe use of insulin vials. PMID- 26681897 TI - The Occurrence of 16 EPA PAHs in Food - A Review. AB - Occurrence and toxicity of polycyclic aromatic hydrocarbons (PAHs) have been extensively studied in countries all over the world. PAHs generally occur in complex mixtures which may consist of hundreds of compounds. The U.S. Environmental Protection Agency (EPA) proposed in the 1970 to monitor a set of 16 PAHs which are frequently found in environmental samples. This article reviews the suitability of the 16 EPA PAHs for the assessment of potential health threats to humans stemming from the exposure to PAHs by food ingestion. It presents details on analysis methods, the occurrence of PAHs in food, regulatory aspects, and related risk management approaches. In addition, consideration is given to newer evaluations of the toxicity of PAHs and the requirements for risk assessment and management stemming from them. PMID- 26681900 TI - New Medical Devices. PMID- 26681899 TI - Pharmacists at Center of Drug Adherence Pilot: Medicare Is Finally Offering More Flexibility for MTM Programs. AB - Pharmacists are the focus of drug adherence pilot program. PMID- 26681901 TI - Pharmaceutical Approval Update. AB - Idarucizumab (Praxbind) to reverse the anticoagulant effects of dabigatran (Pradaxa); aripiprazole lauroxil (Aristada) for the treatment of schizophrenia; and insulin degludec injection (Tresiba) for diabetes. PMID- 26681902 TI - Correction. AB - [This corrects the article on p. 651 in vol. 40, PMID: 26535021.]. PMID- 26681903 TI - Ivabradine (Corlanor) for Heart Failure: The First Selective and Specific I f Inhibitor. AB - Ivabradine (Corlanor) for heart failure: the first selective and specific I f inhibitor. PMID- 26681904 TI - Health Care Consolidation Continues Apace: The Impact on Providers and Patients Is Either Mixed or Unclear. AB - Anthem and Cigna, Aetna and Humana, Walgreens and Rite Aid, Valeant and Salix-the pace of health care mergers is dizzying. Aspects of health care reform that encourage "integrated care" explain some of the frenzy, but by no means all of it. PMID- 26681905 TI - A Comparative Overview of Prescription Omega-3 Fatty Acid Products. AB - An estimated 25% of adults in the United States have elevated triglyceride (TG) levels. This is of particular concern given the evidence for a causal role of TG in the pathway of cardiovascular (CV) disease. Approved prescription omega-3 fatty acid products (RxOM3FAs) contain the long-chain fatty acids docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) and are effective options for the treatment of high TG levels. RxOM3FAs that contain both EPA and DHA include omega 3-acid ethyl esters (ethyl esters of EPA and DHA; brand and generic products) and omega-3-carboxylic acids (free fatty acids primarily composed of EPA and DHA), while the RxOM3FA icosapent ethyl (the ethyl ester of EPA) contains EPA only. All RxOM3FA products produce substantial TG reduction and other beneficial effects on atherogenic lipid and inflammation-related parameters, blood pressure, and heart rate variability, but products that contain DHA may raise low-density lipoprotein cholesterol (LDL-C). This commentary provides an overview of hypertriglyceridemia while summarizing the pharmacology, efficacy, and safety of prescription RxOM3FAs. PMID- 26681907 TI - Effect of Intravenous Acetaminophen on Postoperative Opioid Use in Bariatric Surgery Patients. AB - BACKGROUND: The use of opioids to achieve adequate pain relief following surgery is a common clinical practice. Opioids, however, are associated with serious adverse effects, such as respiratory depression, excessive sedation, and prolonged ileus, as well as increased mortality. The administration of intravenous (IV) acetaminophen to control postoperative pain has been effective in reducing opioid consumption in various surgical populations, but no studies have been conducted in bariatric surgery patients. This investigation was performed to determine whether IV acetaminophen reduces opioid requirements after bariatric surgery. METHODS: IV acetaminophen was added to the Winthrop-University Hospital formulary in September 2012. We conducted a retrospective chart-review analysis of bariatric surgery patients who received at least four doses of IV acetaminophen (1 g every six hours) plus opioids from October 2012 to March 2013 (after IV acetaminophen was added to the hospital formulary), compared with bariatric surgery patients who received only opioids for postoperative pain control from January 2012 to June 2012 (before IV acetaminophen was added to the hospital formulary). The study's primary endpoint was the difference between the two groups in opioid consumption, expressed in oral morphine equivalents (OMEs). Secondary endpoints included the reduction in the baseline pain score; the total amount of each opioid used; and the average hospital length of stay (LOS). RESULTS: A total of 96 patients were identified for potential enrollment from January 2012 to March 2013. Eight patients, however, did not qualify for participation because they had received only one dose of IV acetaminophen. The remaining 88 patients comprised two study groups: IV acetaminophen plus opiates (n = 44) and IV opiates alone (n = 44). Paradoxically, the patients in the acetaminophen/opiates group required significantly more opiates (in OMEs) compared with the group that received opiates alone (median, 93.5 mg versus 63.0 mg, respectively; P = 0.017). There were no significant differences between the two treatment groups in terms of the median change from baseline in pain scores ( 4 versus -4; P = 0.162) or the median hospital LOS (two days versus two days; P = 0.704). CONCLUSION: IV acetaminophen did not reduce opioid use for postoperative pain management in bariatric surgery patients. PMID- 26681908 TI - Practice Guideline Development, Grading, and Assessment. AB - Published clinical practice guidelines (CPGs) are abundant and more easily accessible than ever because of advances in technology and communication and the widespread use of electronic medical literature. To make educated therapy recommendations based on published guidelines, it is important for clinicians to understand the process of guideline development and to be familiar with the resources used to assess guidelines. To do this, clinicians must know the commonly used systems for grading guideline recommendations and for evaluating guideline quality. By increasing their understanding of guideline development, grading, and evaluation processes, clinicians can appropriately use guidelines and provide the highest level of patient care. PMID- 26681906 TI - Parkinson's Disease and Its Management: Part 5: Treatment of Nonmotor Complications. AB - Most patients with Parkinson's disease experience nonmotor complications, broadly classified as either neuropsychiatric presentations or autonomic disorders. Despite the prevalence of these nonmotor features, treatment options for them are limited. PMID- 26681909 TI - Season's Greetings. PMID- 26681910 TI - Spiral Enteroscopy Utilizing Capsule Location Index for Achieving High Diagnostic and Therapeutic Yield. AB - Background and Aim. Spiral enteroscopy (SE) is a new small bowel endoscopic technique. Our aim is to review the diagnostic and therapeutic yield, safety of SE, and the predictive role of prior capsule endoscopy (CE) at an academic center. Methods. A retrospective review of patients undergoing SE after prior CE between 2008 and 2013 was performed. Capsule location index (CLI) was defined as the fraction of total small bowel transit time when the lesion was seen on CE. Results. A total of 174 SEs were performed: antegrade (147) and retrograde (27). Abnormalities on SE were detected in 65% patients. The procedure was safe in patients with surgically altered bowel anatomy (n = 12). The diagnostic yield of antegrade SE decreased with increasing CLI range. The diagnostic yield of retrograde SE decreased on decreasing CLI range. A CLI cutoff of 0.6 was derived that determined the initial route of SE. Vascular ectasias seen on CE were detected in 83% cases on SE; p < 0.01. Conclusions. SE is safe with a high diagnostic and therapeutic yield. CLI is predictive of the success of SE and determines the best route of SE. The type of small bowel pathology targeted by SE may affect its utility and yield. PMID- 26681911 TI - Reproductive Outcomes of Hysteroscopic Septoplasty Techniques. AB - BACKGROUND AND OBJECTIVES: Since little is known regarding the correlation between different techniques used during hysteroscopic septoplasty and reproductives outcomes, we amied to evaluate the results of two different techniques of hysteroscopic septoplasty (HS). METHODS: Data were retrospectively reviewed on 49 patients who underwent HS for symptomatic septate uterus from January 1, 2010, through April 30, 2014. The patients were divided into 2 groups based on the HS technique used. Group I consisted of 27 patients who underwent HS by monopolar hook cautery with the operating hysteroscope. Group II consisted of 22 patients who had the procedure performed with scissors and guided by an office hysteroscope. All the procedures in the both groups were performed in the operating room under general anesthesia. Pregnancy outcomes within the first year after HS for both groups were evaluated. RESULTS: Reproductive outcomes were obtained from 44 patients who attempted to conceive after HS within the first year. In the 25 patients in group I, 23 had pregnancies, of which 15 (65.2%) continued to term, 3 (13%) ended in a preterm live birth, and 5 (21.7%) ended in loss of pregnancy (abortion). In the 19 patients in group II, there were 17 pregnancies, of which 11 (64.7%) continued to term, 2 (11.7%) ended in a preterm live birth, and 4 (23.5%) ended in first- or second-trimester abortion. The overall live-birth rate was 78.2% in group I and 76.4% in group II (P = .85). CONCLUSIONS: Our data show that the rates of pregnancy that reach term and overall rates of live births are similar between the 2 HS techniques. Additional studies are needed to evaluate the impact of the techniques on reproductive outcomes. PMID- 26681912 TI - Electrosurgical Settings and Vaginal Cuff Complications. AB - BACKGROUND AND OBJECTIVES: After being encouraged to change the technique for opening the vaginal cuff during robotic surgery, this study was performed to determine the correlation between vaginal cuff complications and electrosurgical techniques. METHODS: The study group consisted of patients who had their vaginal cuffs opened with a cutting current compared to the group of patients having their vaginal cuff opened with a coagulation current. Data were collected on 150 women who underwent robotic surgery for endometrial cancer. All patients received preoperative antibiotics. Data, including operative time, type of electrosurgery used, estimated blood loss, transfusion rate, and complications, were collected from the patients' records. RESULTS: Surgeries in 150 women and the associated complications were studied. The mean age of the patients was not significantly different between the groups (P = .63). The mean body mass index was 38 kg/m(2) in the coagulation arm and 36 kg/m(2) in the cutting arm (P = .03). Transfusion was not required. Estimated blood loss and operative time were not significantly different in the coagulation versus the cutting arms (P = .29 and .5; respectively). No patients in the cutting arm and 4 patients (with 5 complications) in the coagulation arm had cuff complications (P = .02). CONCLUSIONS: Complications involving the vaginal cuff appear to occur more frequently when the vagina is entered by using electrosurgery with coagulation versus cutting in this cohort of patients undergoing robot-assisted surgery for endometrial cancer.. PMID- 26681913 TI - Eye movements and hazard perception in active and passive driving. AB - Differences in eye movement patterns are often found when comparing passive viewing paradigms to actively engaging in everyday tasks. Arguably, investigations into visuomotor control should therefore be most useful when conducted in settings that incorporate the intrinsic link between vision and action. We present a study that compares oculomotor behaviour and hazard reaction times across a simulated driving task and a comparable, but passive, video-based hazard perception task. We found that participants scanned the road less during the active driving task and fixated closer to the front of the vehicle. Participants were also slower to detect the hazards in the driving task. Our results suggest that the interactivity of simulated driving places increased demand upon the visual and attention systems than simply viewing driving movies. We offer insights into why these differences occur and explore the possible implications of such findings within the wider context of driver training and assessment. PMID- 26681914 TI - Fractionation of a galacto-oligosaccharides solution at low and high temperature using nanofiltration. AB - Like in many applications, solutions of high sugar content can cause serious problems due to microorganism contaminations. Hence, the main aim of this work was to study a nanofiltration process for GOS purification at 5 degrees C and 60 degrees C that may circumvent or reduce potential microbial growth. Process performances and rejection behaviors of monosaccharide as well as individual GOS components were compared. Operating at 5 degrees C is more advantageous especially with respect to the oligosaccharide (OS) recovery yield. Using a NF membrane (NP030) at 45 bar, a product purity of 85% (based on monosaccharide content) and an OS recovery yield of 82% could be achieved. However, a low average permeate flux of 3 L/m2 h had to be accepted. A diafiltration step improved product purity to 90% with 30% losses of OS. A qualitative theoretical discussion shows that a possible change of the pore radius distribution depending on temperature could play a role in solute rejection as well as selectivity. PMID- 26681915 TI - Muscle Transcriptional Profile Based on Muscle Fiber, Mitochondrial Respiratory Activity, and Metabolic Enzymes. AB - Skeletal muscle is a highly metabolically active tissue that both stores and consumes energy. Important biological pathways that affect energy metabolism and metabolic fiber type in muscle cells may be identified through transcriptomic profiling of the muscle, especially ante mortem. Here, gene expression was investigated in malignant hyperthermia syndrome (MHS)-negative Duroc and Pietrian (PiNN) pigs significantly differing for the muscle fiber types slow-twitch oxidative fiber (STO) and fast-twitch-oxidative fiber (FTO) as well as mitochondrial activity (succinate-dependent state 3 respiration rate). Longissimus muscle samples were obtained 24 h before slaughter and profiled using cDNA microarrays. Differential gene expression between Duroc and PiNN muscle samples were associated with protein ubiquitination, stem cell pluripotency, amyloid processing, and 3-phosphoinositide biosynthesis and degradation pathways. In addition, weighted gene co-expression network analysis within both breeds identified several co-expression modules that were associated with the proportion of different fiber types, mitochondrial respiratory activity, and ATP metabolism. In particular, Duroc results revealed strong correlations between mitochondrion associated co-expression modules and STO (r = 0.78), fast-twitch glycolytic fiber (r = -0.98), complex I (r=0.72) and COX activity (r = 0.86). Other pathways in the protein-kinase-activity enriched module were positively correlated with STO (r=0.93), while negatively correlated with FTO (r = -0.72). In contrast to PiNN, co-expression modules enriched in macromolecule catabolic process, actin cytoskeleton, and transcription activator activity were associated with fiber types, mitochondrial respiratory activity, and metabolic enzyme activities. Our results highlight the importance of mitochondria for the oxidative capacity of porcine muscle and for breed-dependent molecular pathways in muscle cell fibers. PMID- 26681916 TI - Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome. AB - Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). We have previously found that amplification of chromosome 6p22 is significantly associated with the muscle-invasive rather than superficial TCC UB. Here, we demonstrated that Sox4, one of the candidate oncogenes located within the chromosome 6p22 amplicon, confers bladder cancer stem cell (CSC) properties. Down-regulation of Sox4 led to the inhibition of cell migration, colony formation as well as mesenchymal-to-epithelial transition (MET). Interestingly, knockdown of Sox4 also reduced the sphere formation, enriched cell population with high levels of aldehyde dehydrogenase (ALDH (high)) and tumor formation potential. Using gene expression profiling, we further identified novel Sox4 target genes. Last, immunohistochemistry analysis of human bladder tumor tissue microarrays (TMAs) indicated that high Sox4 expression was correlated with advanced cancer stages and poor survival rate. In summary, our data show that Sox4 is an important regulator of the bladder CSC properties and it may serve as a biomarker of the aggressive phenotype in bladder cancer. PMID- 26681917 TI - Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome. AB - The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPKalpha expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPKalpha activation (indicated by the ratio of p AMPKalpha to AMPKalpha); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5alpha-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPKalpha activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPKalpha activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPKalpha activation might play a role in the development of endometrial hyperplasia. PMID- 26681919 TI - Microbubbles Enhance the Antitumor Effects of Sinoporphyrin Sodium Mediated Sonodynamic Therapy both In Vitro and In Vivo. AB - OBJECTIVES: To evaluate the anti-cancer effect of sonodynamic therapy combined with microbubbles both in vitro and in vivo. METHODS: Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and guava viacount assays. Annexin V-FITC/PI staining was adopted to analyze cell apoptosis rate. FD500 uptake assay was performed to assess cell membrane permeability changes. Tumor weight, mice weight and the visual image of tumor size were used to reflect the anti-tumor effect of this combined method. Histological change of tumor tissue after different treatments was measured through hematoxylin and eosin (H&E) staining. RESULTS: Microbubbles can significantly enhance the cytotoxicity and necrocytosis rate induced by SDT treatment. Increased cell membrane permeability and more uptake of DVDMS were founded in SDT combined with microbubbles group. For in vivo experiments, SDT with microbubbles can significantly reduce tumor weight and size with pimping difference of mice weight compare with other treatment groups. In addition, microbubbles notably improved tumor tissue destruction caused by ultrasound and SDT treatment. CONCLUSION: The results suggest that microbubbles can markedly improve the anti-cancer effect of DVDMS mediate sonodynamic therapy both in vitro and in vivo. PMID- 26681920 TI - Precision Medicine for Personalized Cancer Therapy. PMID- 26681918 TI - Targeting Tumor Metabolism for Cancer Treatment: Is Pyruvate Dehydrogenase Kinases (PDKs) a Viable Anticancer Target? AB - Cancer remains a lethal threat to global lives. Development of novel anticancer therapeutics is still a challenge to scientists in the field of biomedicine. In cancer cells, the metabolic features are significantly different from those of normal ones, which are hallmarks of several malignancies. Recent studies brought atypical cellular metabolism, such as aerobic glycolysis or the Warburg effect, into the scientific limelight. Targeting these altered metabolic pathways in cancer cells presents a promising therapeutic strategy. Pyruvate dehydrogenase kinases (PDKs), key enzymes in the pathway of glucose metabolism, could inactivate the pyruvate dehydrogenase complex (PDC) by phosphorylating it and preserving the substrates pyruvate, lactate and alanine for gluconeogenesis. Overexpression of PDKs could block the oxidative decarboxylation of pyruvate to satisfy high oxygen demand in cancer cells, while inhibition of PDKs could upregulate the activity of PDC and rectify the balance between the demand and supply of oxygen, which could lead to cancer cell death. Thus, inhibitors targeting PDKs represent a promising strategy for cancer treatment by acting on glycolytic tumors while showing minimal side effects on the oxidative healthy organs. This review considers the role of PDKs as regulator of PDC that catalyzes the oxidative decarboxylation of pyruvate in mitochondrion. It is concluded that PDKs are solid therapeutic targets. Inhibition of PDKs could be an attractive therapeutic approach for the development of anti-cancer drugs. PMID- 26681922 TI - Inhibition of mTOR Pathway by Rapamycin Reduces Brain Damage in Rats Subjected to Transient Forebrain Ischemia. AB - The aims of this study are to clarify the role of mTOR in mediating cerebral ischemic brain damage and the effects of rapamycin on ischemic outcomes. Ten minutes of forebrain ischemia was induced in rats, and their brains were sampled after 3 h, 16 h, and 7 days reperfusion for histology, immunohistochemistry and biochemical analysis. Our data demonstrated that cerebral ischemia resulted in both apoptotic and necrotic neuronal death; cerebral ischemia and reperfusion led to significant increases of mRNA and protein levels of p-mTOR and its downstream p-P70S6K and p-S6; elevation of LC3-II, and release of cytochrome c into the cytoplasm in both the cortex and hippocampus. Inhibition of mTOR by rapamycin markedly reduced ischemia-induced damage; suppressed p-Akt, p-mTOR, p-P70S6K and p-S6 protein levels; decreased LC3-II and Beclin-1; and prevented cytochrome c release in the two structures. All together, these data provide evidence that cerebral ischemia activates mTOR and autophagy pathways. Inhibition of mTOR deactivates the mTOR pathway, suppresses autophagy, prevents cytochrome c release and reduces ischemic brain damage. PMID- 26681921 TI - To Know How a Gene Works, We Need to Redefine It First but then, More Importantly, to Let the Cell Itself Decide How to Transcribe and Process Its RNAs. AB - Recent genomic and ribonomic research reveals that our genome produces a stupendous amount of non-coding RNAs (ncRNAs), including antisense RNAs, and that many genes contain other gene(s) in their introns. Since ncRNAs either regulate the transcription, translation or stability of mRNAs or directly exert cellular functions, they should be regarded as the fourth category of RNAs, after ribosomal, messenger and transfer RNAs. These and other research advances challenge the current concept of gene and raise a question as to how we should redefine gene. We can either consider each tiny part of the classically-defined gene, such as each mRNA variant, as a "gene", or, alternatively and oppositely, regard a whole genomic locus as a "gene" that may contain intron-embedded genes and produce different types of RNAs and proteins. Each of the two ways to redefine gene not only has its strengths and weaknesses but also has its particular concern on the methodology for the determination of the gene's function: Ectopic expression of complementary DNA (cDNA) in cells has in the past decades provided us with great deal of detail about the functions of individual mRNA variants, and will make the data less conflicting with each other if just a small part of a classically-defined gene is considered as a "gene". On the other hand, genomic DNA (gDNA) will better help us in understanding the collective function of a genomic locus. In our opinion, we need to be more cautious in the use of cDNA and in the explanation of data resulting from cDNA, and, instead, should make delivery of gDNA into cells routine in determination of genes' functions, although this demands some technology renovation. PMID- 26681923 TI - A20 Attenuates FFAs-induced Lipid Accumulation in Nonalcoholic Steatohepatitis. AB - A20 is a ubiquitin-editing enzyme that attenuates the activity of proximal signaling complexes at pro-inflammatory receptors. It has been well documented that A20 protein plays an important role in response to liver injury and hepatocytes apoptosis in pro-inflammatory pathways. However, there was little evidence showing that A20 protein was involving in fatty-acid homeostasis except the up-regulation of two fatty acid metabolism regulatory genes at mRNA level (PPARa and CPT1a) by adenovirus-mediated A20 protein overexpression. In this study we found that: 1) the expression level of A20 protein was significantly higher in the steatotic liver from MCD-fed mice than the controls; 2) Overexpression of A20 protein suppressed FFAs-stimulated triglyceride deposition in HepG2 cells while under expression of A20 protein increased FFAs-stimulated triglyceride deposition; 3) Overexpression of A20 protein in HepG2 cells upregulated genes that promote beta-oxidation and decreased the mRNA levels of key lipogenic genes such as fatty acid synthase (FAS), indicating A20 function as anti-steatotic factor by the activation of mitochondrial beta-oxidation and attenuation of de novo lipogenesis; 4) Nonalcoholic steatohepatitis (NASH) patients showed significantly higher A20 expression level in liver compared with control individuals. Our results demonstrated that A20 protein plays an important role in fatty-acid homeostasis in human as well as animals. In addition, our data suggested that the pathological function of A20 protein in hepatocyte from lipotoxicity to NASH is by the alleviation of triglyceride accumulation in hepatocytes. Elevated expression of A20 protein could be a potential therapeutic strategy for preventing the progression of nonalcoholic steatohepatitis. PMID- 26681925 TI - Kruppel-Like Factor 5 Promotes Epithelial Proliferation and DNA Damage Repair in the Intestine of Irradiated Mice. AB - BACKGROUND & AIMS: High doses of radiation induce severe DNA damage in intestinal epithelial cells, especially crypt cells, and cause intestinal injury, but the underlying molecular mechanisms remain unclear. Kruppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is induced by various stress stimuli and is involved in cell proliferation and survival. The role of KLF5 in radiation induced intestinal injury was investigated here. METHODS: Wild type mice were treated with 8 or 15 Gy total body irradiation (TBI). KLF5 content and cellular localization in the small intestines of irradiated mice were detected by Western blot and immunohistochemical analysis. Mice with intestinal-specific knockdown of KLF5 (Vil-Cre; Klf5(fl/+) mice) were generated and their response to radiation was compared with controls. Morphological changes were determined by hematoxylin and eosin staining. Proliferation was examined by Ki67 immunostaining. The molecular response of the small intestine after KLF5 knockdown was investigated using microarrays. RESULTS: KLF5 expression correlated with the progression of intestinal damage. Decreased levels of KLF5 in the gut were associated with increased damage to the intestinal mucosa and reduced epithelial proliferation after TBI. Our microarray data disclosed that KLF5 knockdown down-regulated genes related to DNA damage repair pathways such as nucleotide excision repair, mismatch repair, non-homologous end joining and the Fanconi anemia pathway, which may suggest a novel function of KLF5. CONCLUSIONS: Our study illustrates that KLF5 may modulate DNA repair pathways to prevent intestinal injury induced by TBI. KLF5 signaling provides a novel field for identification of potential therapeutic targets for the treatment of radiation-induced intestinal damage. PMID- 26681924 TI - Knockout of the Histone Demethylase Kdm3b Decreases Spermatogenesis and Impairs Male Sexual Behaviors. AB - Kdm3b is a JmjC domain-containing histone H3 (H3) demethylase and its physiological functions are largely unknown. In this study, we found that Kdm3b protein is highly expressed in multiple cell types in the mouse testes, including Leydig cells, Sertoli cells, spermatogonia and spermatocytes at different differentiation stages. We also observed Kdm3b protein in the epithelial cells of the caput epididymis, prostate and seminal vesicle. Breeding tests revealed that the number of pups produced by the breeding pairs with Kdm3b knockout (Kdm3bKO) males and wild type (WT) females was reduced 68% because of the decreased number of litters when compared with the breeding pairs with WT males and females. Further analysis demonstrated that Kdm3bKO male mice produced 44% fewer number of mature sperm in their cauda epididymides, displaying significantly reduced sperm motility. No significant differences in the circulating concentration of testosterone and the expression levels of androgen receptor and its representative target genes in the testis were observed. However, the circulating levels of 17beta-estradiol, a modulator of sperm maturation and male sexual behaviors, was markedly reduced in Kdm3bKO male mice. Strikingly, abrogation of Kdm3b in male mice significantly increased the latencies to mount, intromit and ejaculate and decreased the number of mounts and intromissions, largely due to their loss of interest in female odors. These findings indicate that Kdm3b is required for normal spermatogenesis and sexual behaviors in male mice. PMID- 26681926 TI - Rethinking paradigms for studying mechanisms of action of plant bioactives. AB - Many foods in our diets such as berries, tea, chocolate and wine contain flavonoids, which are natural components of plants. A substantial body of evidence supports the role of flavonoids in providing protection against cardio metabolic diseases and disorders. Despite the nearly exponential growth in flavonoid research in the past 20 years, limited progress has been made in understanding how these dietary components work. Research initially focused on their antioxidant activity without taking into account their metabolism, which now appears extensive. This has provided a new research impetus to understand the biological activity of the flavonoid metabolites. Here, we outline recent research, which suggests a highly complex interplay between metabolism, intestinal microflora, the immune system and various tissues of our body. PMID- 26681927 TI - Considerations for a Primary Care Physician Assistant in Treating Kidney Transplant Recipients. AB - The escalating amount of kidney transplant recipients (KTRs) represents a significant dilemma for primary care providers. As the number of physician assistants (PAs) has been steadily increasing in primary care in the United States, the utilization of these healthcare professionals presents a solution for the care of post-kidney transplant recipients. A physician assistant (PA) is a state licensed healthcare professional who practices medicine under physician supervision and can alleviate some of the increasing demands for primary patient care. Here we provide an outline of the crucial components and considerations for PAs caring for kidney transplant recipients. These include renal function and routine screenings, drug monitoring (both immunosuppressive and therapeutic), pre existing and co-existing conditions, immunizations, nutrition, physical activity, infection, cancer, and the patient's emotional well-being. PAs should routinely monitor renal function and blood chemistry of KTRs. Drug monitoring of KTRs is a crucial responsibility of the PA because of the possible side-effects and potential drug-drug interactions. Therefore, PAs should obtain a careful and detailed patient history from KTRs. PAs should be aware of pre- and co-existing conditions of KTRs as this impacts treatment decisions. Regarding immunization, PAs should avoid administering vaccines containing live or attenuated viruses to KTRs. Because obesity following kidney transplantation is associated with decreased allograft survival, PAs should encourage KTRs to maintain a balanced diet with limited sugar. In addition, KTRs should be urged to gradually increase their levels of physical activity over subsequent years following surgery. PAs should be aware that immunosuppressive medications diminish immune defenses and make KTRs more susceptible to bacterial, viral, and fungal infections. Moreover, KTRs should be screened routinely for cancer due to the higher risk of development from immunosuppressive therapy. PAs must remain cognizant of the emotional well-being of the KTR, as many transplant patients struggle with fear, frustration, and acceptance. PMID- 26681928 TI - Research Priorities in Mental Health, Justice, and Safety: A Multidisciplinary Stakeholder Report. AB - This paper is based on the report following the National Research Agenda Meeting on Mental Health, Justice, and Safety held in Montreal on November 19, 2014, which convened academics; health, social, and legal professionals; and people with lived experience of mental illness from across Canada. The goal was to identify research priorities addressing relevant knowledge gaps and research strategies that can translate into public policy action and improvements in evidence-based services. Participants identified key challenges: (1) inadequate identification and response to needs by civil mental health services and frontline law enforcement, (2) limited specialized resources in forensic and correctional settings, (3) fragmented care and gaps between systems, (4) limited resources for adequate community reintegration, and (5) poor knowledge transfer strategies as obstacles to evidence-based policies. Knowledge gaps were identified in epidemiology and risk reduction, frontline training and programs, forensic and correctional practices, organizations and institutions, knowledge transfer, and rehabilitation. Finally, participants identified potential sources of support to conduct real time research with regard to data collection and sharing. The findings represent a roadmap for how forensic mental health systems can best proceed to address current challenges through research and practice initiatives, drawing from lived, clinical and research experiences of a multidisciplinary group of experts. PMID- 26681929 TI - Operational Changes in a Shared Resource Laboratory with the Use of a Product Lifecycle Management Approach: A Case Study. AB - Shared Resource Laboratories (SRLs) provide investigators access to necessary scientific and resource expertise to leverage complex technologies fully for advancing high-quality biomedical research in a cost-effective manner. At the University of Nebraska Medical Center, the Flow Cytometry Research Facility (FCRF) offered access to exceptional technology, but the methods of operation were outdated and unsustainable. Whereas technology has advanced and the institute has expanded, the operations at the facility remained unchanged for 35 yr. To rectify this, at the end of 2013, we took a product lifecycle management approach to affect large operational changes and align the services offered with the SRL goal of education, as well as to provide service to researchers. These disruptive operational changes took over 10 mo to complete and allowed for independent end-user acquisition of flow cytometry data. The results have been monitored for the past 12 mo. The operational changes have had a positive impact on the quality of research, increased investigator-facility interaction, reduced stress of facility staff, and increased overall use of the resources. This product lifecycle management approach to facility operations allowed us to conceive of, design, implement, and monitor effectively the changes at the FCRF. This approach should be considered by SRL management when faced with the need for operationally disruptive measures. PMID- 26681930 TI - Efficient Approximation of Head-Related Transfer Functions in Subbands for Accurate Sound Localization. AB - Head-related transfer functions (HRTFs) describe the acoustic filtering of incoming sounds by the human morphology and are essential for listeners to localize sound sources in virtual auditory displays. Since rendering complex virtual scenes is computationally demanding, we propose four algorithms for efficiently representing HRTFs in subbands, i.e., as an analysis filterbank (FB) followed by a transfer matrix and a synthesis FB. All four algorithms use sparse approximation procedures to minimize the computational complexity while maintaining perceptually relevant HRTF properties. The first two algorithms separately optimize the complexity of the transfer matrix associated to each HRTF for fixed FBs. The other two algorithms jointly optimize the FBs and transfer matrices for complete HRTF sets by two variants. The first variant aims at minimizing the complexity of the transfer matrices, while the second one does it for the FBs. Numerical experiments investigate the latency-complexity trade-off and show that the proposed methods offer significant computational savings when compared with other available approaches. Psychoacoustic localization experiments were modeled and conducted to find a reasonable approximation tolerance so that no significant localization performance degradation was introduced by the subband representation. PMID- 26681931 TI - Synthesis, DFT Calculation, and Antimicrobial Studies of Novel Zn(II), Co(II), Cu(II), and Mn(II) Heteroleptic Complexes Containing Benzoylacetone and Dithiocarbamate. AB - Heteroleptic complexes of zinc(II), copper(II), manganese(II), and cobalt(II) of the types [MLL'(H2O)2].nH2O and [MLL'].nH2O have been synthesized using sodium N methyl-N-phenyldithiocarbamate (L) and benzoylacetone (L'). The metal complexes were characterized by elemental analysis, electrical conductance, magnetic susceptibility, infrared (IR), and UV-visible spectroscopic studies. The electrical conductance measurements revealed the nonelectrolytic nature of the synthesized complexes. The results of the elemental analyses, magnetic susceptibility measurements, and electronic spectra inferred that the Zn(II) complex adopted a four-coordinate geometry while the Co(II), Cu(II), and Mn(II) complexes assumed octahedral geometries. The IR spectra showed that the metal ions coordinated with the ligands via the S- and O-donor atoms. The geometry, electronic, and thermodynamic parameters of the complexes were obtained from density functional theory (DFT) calculations. The spin density distributions, relative strength of H-bonds, and thermodynamic parameters revealed that the order of stability of the metal complexes is Mn < Co < Cu > Zn. The agar diffusion methods were used to study the antimicrobial activity of the complexes against two Gram positive bacteria (S. aureus and S. pneumoniae), one Gram negative bacterium (E. coli), and two fungi organisms (A. niger and A. candida) and the complexes showed a broad spectrum of activities against the microbes. PMID- 26681932 TI - Timing of union formation and partner choice in immigrant societies: The United States and Germany. AB - As Gordon noted in his 1964 treatise on assimilation, marriage across ethnic boundaries and in particular, marriage into the mainstream is a key indicator as well as a mechanism of immigrant assimilation. Since then research has investigated numerous micro- and macro level correlates of exogamy. In this paper we focus on a topic that has received less attention thus far - how the timing of marriage is associated with partner choice. We compare the United States and Germany as two countries with significant immigrant and second-generation populations but where mainstream patterns of union formation differ. In both contexts we show that unions that cross ethnic boundaries happen later in life than those that stay within. Comparing across countries we argue that in Germany differences in the timing of union formation between the second generation and the mainstream, may pose additional barriers to intermarriage that do not exist in the United States. PMID- 26681933 TI - MapReduce Based Parallel Neural Networks in Enabling Large Scale Machine Learning. AB - Artificial neural networks (ANNs) have been widely used in pattern recognition and classification applications. However, ANNs are notably slow in computation especially when the size of data is large. Nowadays, big data has received a momentum from both industry and academia. To fulfill the potentials of ANNs for big data applications, the computation process must be speeded up. For this purpose, this paper parallelizes neural networks based on MapReduce, which has become a major computing model to facilitate data intensive applications. Three data intensive scenarios are considered in the parallelization process in terms of the volume of classification data, the size of the training data, and the number of neurons in the neural network. The performance of the parallelized neural networks is evaluated in an experimental MapReduce computer cluster from the aspects of accuracy in classification and efficiency in computation. PMID- 26681934 TI - Optimism in Active Learning. AB - Active learning is the problem of interactively constructing the training set used in classification in order to reduce its size. It would ideally successively add the instance-label pair that decreases the classification error most. However, the effect of the addition of a pair is not known in advance. It can still be estimated with the pairs already in the training set. The online minimization of the classification error involves a tradeoff between exploration and exploitation. This is a common problem in machine learning for which multiarmed bandit, using the approach of Optimism in the Face of Uncertainty, has proven very efficient these last years. This paper introduces three algorithms for the active learning problem in classification using Optimism in the Face of Uncertainty. Experiments lead on built-in problems and real world datasets demonstrate that they compare positively to state-of-the-art methods. PMID- 26681935 TI - Surgical Approaches to Chronic Pancreatitis. AB - Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients. PMID- 26681936 TI - Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study. AB - The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg). PMID- 26681937 TI - High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism. AB - Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30-300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg(-1) min(-1), Ang II reduced RBF by 45.7 +/- 1.9% in estradiol-treated rats but only by 27.3 +/- 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. PMID- 26681938 TI - Acridine Orange and Flow Cytometry: Which Is Better to Measure the Effect of Varicocele on Sperm DNA Integrity? AB - We evaluated the effect of varicocelectomy on semen parameters and levels of sperm DNA damage in infertile men. A total of 75 infertile men with varicocele and 40 fertile men (controls) were included in this study. Semen analysis and sperm DNA damage expressed as the DNA fragmentation index using acridine orange staining and chromatin condensation test by flow cytometry were assessed before and 6 months after varicocelectomy. The patients were also followed up for 1 year for pregnancy outcome. Semen parameters were significantly lower in varicocele patients compared to controls (P < 0.05). Mean percentages of sperm DNA fragmentation and sperm DNA chromatin condensation in patients were significantly higher than those in controls (P < 0.05). After varicocelectomy, sperm DNA fragmentation improved significantly, whereas sperm chromatin condensation was not significantly changed. In 15 out of 75 varicocele patients, clinical pregnancy was diagnosed; those with positive pregnancy outcome had significant improvement in sperm count, progressive sperm motility, and sperm DNA fragmentation, but there was no significant difference in sperm DNA condensation compared to negative pregnancy outcome patients. We concluded from this study that acridine orange stain is more reliable method than flow cytometry in the evaluation of sperm DNA integrity after varicocelectomy. PMID- 26681939 TI - Low Serum Vitamin D Is Associated with Anti-Thyroid-Globulin Antibody in Female Individuals. AB - Objectives. Some evidence has pointed out that vitamin D plays a significant role in reducing the incidence of autoimmune diseases, especially autoimmune thyroid diseases. The authors aimed to examine the relationship between circulating 25 hydroxyvitamin D and thyroid autoantibody in a population-based health survey of Xinjiang Chinese population. Subjects and Methods. A total of 1714 Chinese adults were analyzed. 25(OH)D, anti-thyroid antibodies, and thyroid function were measured. Results. The prevalence of vitamin D insufficiency was 28.3% in Hans and 9.3% in Uyghurs, and the prevalence of vitamin D deficiency was 61.6% in Hans and 87.6% in Uyghurs. Overall prevalence of TgAb positivity was 6.2% (0.9% males; 5.3% females). In female subjects, mean serum 25(OH)D levels were significantly lower in Hans and Uyghurs compared with males, and the difference was statistically significant. Importantly, after adjusting for age and ethnicity, a negative correlation (r = -0.121, P = 0.014) was recognized between 25(OH)D and TgAb levels only in female subjects. Conclusion. Vitamin D insufficiency and deficiency are prevalent among Chinese adults. Low serum 25(OH)D is related to the presence of TgAb in females. The causal effect of low vitamin D level on thyroid autoimmunity should be studied further more. PMID- 26681940 TI - Safety Profile and Effects of Pulsed Methylprednisolone on Vital Signs in Thyroid Eye Disease. AB - Objective. To analyze changes in vital signs (heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP)) during and after intravenous methylprednisolone (IVMP) and any other adverse effects. Methods. Retrospective review of charts of patients who received IVMP as treatment regime for thyroid eye disease. All subjects had vital signs charted during and after infusions. Results. This study included 38 subjects and a total of 242 infusions administered. IVMP resulted in a small but significant percentage drop in mean SBP at 30 min (p < 0.001) and 60 min (p = 0.03) but no difference at 90 min. There was also small but significant percentage drop in mean DBP and HR (DBP: p < 0.001 for 30 min, p = 0.001 for 60 min, and p = 0.02 for 90 min and HR: p < 0.001 for 30 min, 60 min, and 90 min). There were no cumulative effects on change of blood pressure or HR. There were 6 episodes of bradycardia (2.5%) and 12 episodes of moderate to severe hypertension (5%). No significant cardiovascular or hepatic toxicity was found. Conclusion. IVMP is relatively safe and efficacious. IVMP demonstrated mild and noncumulative effects on vital signs. Severe hypertension may occur in susceptible individuals such as those with underlying hypertension and uncontrolled thyroid dysfunction, whereas bradycardia may be more likely in those on beta-blockers. PMID- 26681941 TI - Glycolipid Metabolism Disorder in the Liver of Obese Mice Is Improved by TUDCA via the Restoration of Defective Hepatic Autophagy. AB - Objective. Tauroursodeoxycholic acid (TUDCA) has been considered an important regulator of energy metabolism in obesity. However, the mechanism underlying how TUDCA is involved in insulin resistance is not fully understood. We tested the effects of TUDCA on autophagic dysfunction in obese mice. Material and Methods. 500 mg/kg of TUDCA was injected into obese mice, and metabolic parameters, autophagy markers, and insulin signaling molecular were assessed by Western blotting and real-time PCR. Results. The TUDCA injections in the obese mice resulted in a reduced body weight gain, lower blood glucose, and improved insulin sensitivity compared with obese mice that were injected with vehicle. Meanwhile, TUDCA treatment not only reversed autophagic dysfunction and endoplasmic reticulum stress, but also improved the impaired insulin signaling in the liver of obese mice. Additionally, the same results obtained with TUDCA were evident in obese mice treated with the adenoviral Atg7. Conclusions. We found that TUDCA reversed abnormal autophagy, reduced ER stress, and restored insulin sensitivity in the liver of obese mice and that glycolipid metabolism disorder was also improved via the restoration of defective hepatic autophagy. PMID- 26681942 TI - Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection. AB - Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31-85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60-100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate. PMID- 26681943 TI - Patterns of Benign and Malignant Lesions of the Thyroid in Two Wilayahs of Northeastern Algeria. AB - The aim of this study is to compare histological patterns and to estimate the burden of thyroid cancers in the two Wilayahs (departments) of El-Taref and Guelma in northeast of Algeria (total population 0.9 million), locally reputed as having different rates of endemic thyroid diseases and cancer. A retrospective analysis of central pathology registers and clinical records of patients with thyroid diseases, covering the period 2008-2012, was conducted. A total of 145 cases of thyroid cancers with histological confirmation were registered in the two Wilayahs during the period, with a female to male ratio of 5.9 : 1. Estimates of crude incidence rates suggested that thyroid cancers were twice as frequent in the Wilayah of Guelma compared to El-Taref (p < 0.05) with a tendency to occur at a younger age in resident of the Wilayah of El-Taref. Diagnoses of thyroid adenoma were more frequent in the Wilayah of Guelma, whereas the prevalence of other thyroid lesions, including goitre, was similar in the two Wilayahs. This first descriptive study on geographic variations in thyroid cancer in Northern Africa suggests that significant differences may occur in relation with environmental and lifestyle exposures. PMID- 26681944 TI - Cone-Beam Computed Tomographic Assessment of Mandibular Condylar Position in Patients with Temporomandibular Joint Dysfunction and in Healthy Subjects. AB - Statement of the Problem. The clinical significance of condyle-fossa relationships in the temporomandibular joint is a matter of controversy. Different studies have evaluated whether the position of the condyle is a predictor of the presence of temporomandibular disorder. Purpose. The purpose of the present study was to investigate the condylar position according to gender in patients with temporomandibular disorder (TMD) and healthy controls using cone beam computed tomography. Materials and Methods. CBCT of sixty temporomandibular joints in thirty patients with TMD and sixty joints of thirty subjects without TMJ disorder was evaluated in this study. The condylar position was assessed on the CBCT images. The data were analyzed using Pearson chi-square test. Results. No statistically significant differences were found regarding the condylar position between symptomatic and asymptomatic groups. Posterior condylar position was more frequently observed in women and anterior condylar position was more prevalent in men in the symptomatic group. However, no significant differences in condylar position were found in asymptomatic subjects according to gender. Conclusion. This study showed no apparent association between condylar positioning and clinical findings in TMD patients. PMID- 26681945 TI - Ceruminous Adenoma of the External Auditory Canal: A Case Report with Imaging and Pathologic Findings. AB - Ceruminous adenomas are benign tumors that are rare in humans and present with a nonspecific symptomatology. The treatment of choice is surgical excision. We present an 87-year-old woman who presented with a reddish, tender, round, soft mass of the outer third of the inferior wall of the left external auditory canal, discharging a yellowish fluid upon pressure. Coincidentally, due to her poor general condition, this patient also showed symptoms consistent with chronic otitis media, parotitis, and cervical lymphadenopathy, such as otorrhea, through a ruptured tympanic membrane and swelling of the parotid gland and cervical lymph nodes. The external auditory canal lesion was surgically excised under general anesthesia, utilizing a transmeatal approach. The pathological diagnosis was ceruminous gland adenoma. The tumor was made of tubular and cystic structures and embedded in a fibrous, focally hyalinized stroma. Immunohistochemistry confirmed the presence of two distinct cell populations. The luminal cells expressed keratin 7, while peripheral (basal) cells expressed keratins 5/6, S100 protein, and p63. The apocrine gland-related antigen GCDFP-15 was focally expressed by tumor cells. The postoperative course was uneventful and at the 2-year follow-up no recurrence of the ceruminous adenoma was noted. PMID- 26681946 TI - Right Upper Lobe Shadow and Tracheobronchopathia Osteochondroplastica Confined to Right Main Bronchus: A Case Report and Literature Review. AB - Tracheobronchopathia osteochondroplastica (TO) is a well documented benign entity of endoscopic interest. We describe a case of 76-year-old patient who presented with fever, cough, purulent sputum during the past four days, and presence of an ovoid shadow in right upper zone of his chest X-ray. Medical history included diagnosis of colon diverticuli identified by colonoscopy 3 months ago. Chest CT revealed a compact elongated lesion containing air-bronchogram stripes. Bronchoscopy showed normal upper airways and trachea but presence of unequal sized mucosal nodules, protruding into the lumen, along the entire length of the right main bronchial mucosa. No other abnormal findings were detected. Moreover, brushing and washing smears from the apical segment of right upper lobe (RUL), where the compact lesion was located, were negative for malignancy. Biopsy from the mucosal nodules of right main bronchus showed presence of cartilaginous tissue in continuity through thin pedicles with submucosal cartilage. This finding posed the diagnosis of TO while RUL lesion was cleared by antibiotic treatment. Case is reported because, to our knowledge, it represents a unique anatomic location of TO which was confined exclusively in the right main bronchus mucosa without affecting trachea. PMID- 26681947 TI - Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland Presenting as Incidental Adrenal Masses. AB - Although lymphoma may occasionally involve the adrenal glands as part of a generalized disease process, primary adrenal lymphoma (PAL) is a rare disease. We present a case of a 62-year-old woman with a history of mild/moderate hereditary spherocytosis with a well-compensated baseline haemoglobin, who presented with rapidly progressive symptomatic anaemia. During the diagnostic workup, imaging revealed bilateral large adrenal masses and she was later diagnosed with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), with the adrenal glands being the dominant site of the disease. The patient was started on systemic chemotherapy, but her disease progressed with neurological involvement which responded to second-line therapy. Her adrenal disease however was refractory to further therapy. PMID- 26681948 TI - Endometrial Mesenchymal Stem Cells Isolated from Menstrual Blood by Adherence. AB - Objective. To find a convenient and efficient way to isolate MSCs from human menstrual blood and to investigate their biological characteristics, proliferative capacity, and secretion levels. Methods. MSCs were isolated from menstrual blood of 3 healthy women using adherence. Cell immunological phenotype was examined by flow cytometry; the adipogenic, osteogenic, and chondrogenic differentiation of MSCs was examined by Oil-Red-O staining, ALP staining, and Alcian Blue staining, respectively; and the secretion of cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1), was detected using enzyme-linked immunosorbent assay. Results. MB-MSCs were successfully isolated from human menstrual blood using adherence. They were positive for CD73, CD105, CD29, and CD44, but negative for CD31 and CD45. The differentiated MB-MSCs were positive for ALP staining, Oil-Red-O staining, and Alcian Blue staining. In addition, they could secrete antiapoptotic cytokines, such as VEGF, IGF-1, and HGF. Conclusion. It is feasible to isolate MSCs from human menstrual blood, thus avoiding invasive procedures and ethical controversies. Adherence could be a promising alternative to the density gradient centrifugation for the isolation of MSCs from menstrual blood. PMID- 26681949 TI - Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells. AB - The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs). We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C), known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis. PMID- 26681951 TI - Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation. AB - Current approaches in human embryonic stem cell (hESC) to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin-1 (LGALS1), Neuroplastin (NPTN), and the Laminin alpha-2 subunit (LAMA2). Two of the three factors (LGALS1 and LAMA2) increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation. PMID- 26681950 TI - Epigenetic Control of Haematopoietic Stem Cell Aging and Its Clinical Implications. AB - Aging, chronic inflammation, and environmental insults play an important role in a number of disease processes through alterations of the epigenome. In this review we explore how age-related changes in the epigenetic landscape can affect heterogeneity within the haematopoietic stem cell (HSC) compartment and the deriving clinical implications. PMID- 26681952 TI - Transcriptome Analysis of Long Noncoding RNAs in Toll-Like Receptor 3-Activated Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) possess great immunomodulatory capacity which lays the foundation for their therapeutic effects in a variety of diseases. Recently, toll-like receptors (TLR) have been shown to modulate MSC functions; however, the underlying molecular mechanisms are poorly understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are an important class of regulators involved in a wide range of biological processes. To explore the potential involvement of lncRNAs in TLR stimulated MSCs, we performed a comprehensive lncRNA and mRNA profiling through microarray. 10.2% of lncRNAs (1733 out of 16967) and 15.1% of mRNA transcripts (1760 out of 11632) were significantly differentially expressed (absolute fold-change >=5 , P value <=0.05) in TLR3 stimulated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Here, we are the first to determine genome-wide lncRNAs expression patterns in TLR3 stimulated MSCs by microarray and this work could provide a comprehensive framework of the transcriptome landscapes of TLR3 stimulated MSCs. PMID- 26681953 TI - Adiponectin Isoforms and Leptin Impact on Rheumatoid Adipose Mesenchymal Stem Cells Function. AB - Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA-FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA-ASCs secreted spontaneously TGFbeta, IL-6, IL-1Ra, PGE2, IL-8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC-derived soluble factors on RA-FLS but did not affect IL-6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti-inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL-10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA FLS and PBMCs. PMID- 26681954 TI - Epigenetics and Shared Molecular Processes in the Regeneration of Complex Structures. AB - The ability to regenerate complex structures is broadly represented in both plant and animal kingdoms. Although regenerative abilities vary significantly amongst metazoans, cumulative studies have identified cellular events that are broadly observed during regenerative events. For example, structural damage is recognized and wound healing initiated upon injury, which is followed by programmed cell death in the vicinity of damaged tissue and a burst in proliferation of progenitor cells. Sustained proliferation and localization of progenitor cells to site of injury give rise to an assembly of differentiating cells known as the regeneration blastema, which fosters the development of new tissue. Finally, preexisting tissue rearranges and integrates with newly differentiated cells to restore proportionality and function. While heterogeneity exists in the basic processes displayed during regenerative events in different species-most notably the cellular source contributing to formation of new tissue-activation of conserved molecular pathways is imperative for proper regulation of cells during regeneration. Perhaps the most fundamental of such molecular processes entails chromatin rearrangements, which prime large changes in gene expression required for differentiation and/or dedifferentiation of progenitor cells. This review provides an overview of known contributions to regenerative processes by noncoding RNAs and chromatin-modifying enzymes involved in epigenetic regulation. PMID- 26681956 TI - Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity. AB - Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPalpha, PPARgamma, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels. PMID- 26681955 TI - A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements. AB - Transposons are mobile genetic elements that threaten the survival of species by destabilizing the germline genomes. Limiting the spread of these selfish elements is imperative. Germ cells employ specialized small regulatory RNA pathways to restrain transposon activity. PIWI proteins and Piwi-interacting RNAs (piRNAs) silence transposons at the transcriptional and posttranscriptional level with loss-of-function mutant animals universally exhibiting sterility often associated with germ cell defects. This short review aims to illustrate basic strategies of piRNA-guided defense against transposons. Mechanisms of piRNA silencing are most readily studied in Drosophila melanogaster, which serves as a model to delineate molecular concepts and as a reference for mammalian piRNA systems. PiRNA pathways utilize two major strategies to handle the challenges of transposon control: (1) the hard-wired molecular memory of prior transpositions enables recognition of mobile genetic elements and discriminates transposons from host genes; (2) a feed forward adaptation mechanism shapes piRNA populations to selectively combat the immediate threat of transposon transcripts. In flies, maternally contributed PIWI piRNA complexes bolster both of these lines of defense and ensure transgenerational immunity. While recent studies have provided a conceptual framework of what could be viewed as an ancient immune system, we are just beginning to appreciate its many molecular innovations. PMID- 26681957 TI - Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin. AB - Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis, since it is usually diagnosed at advanced stages. In order to employ tools for early detection, a better understanding of the early stages of PDA development from its main precursors, pancreatic intraepithelial neoplasia (PanIN), and intraductal papillary mucinous neoplasm (IPMN) is needed. Recent studies on murine PDA models have identified a different exocrine origin for PanINs and IPMNs. In both processes, developmental pathways direct the initiation of PDA precursors from their cellular ancestors. In this review, the current understanding of early PDA development is summarized. PMID- 26681959 TI - Genome-Wide Prediction of Vaccine Candidates for Leishmania major: An Integrated Approach. AB - Despite the wealth of information regarding genetics of the causative parasite and experimental immunology of the cutaneous leishmaniasis, there is currently no licensed vaccine against it. In the current study, a two-level data mining strategy was employed, to screen the Leishmania major genome for promising vaccine candidates. First, we screened a set of 25 potential antigens from 8312 protein coding sequences, based on presence of signal peptides, GPI anchors, and consensus antigenicity predictions. Second, we conducted a comprehensive immunogenic analysis of the 25 antigens based on epitopes predicted by NetCTL tool. Interestingly, results revealed that candidate antigen number 1 (LmjF.03.0550) had greater number of potential T cell epitopes, as compared to five well-characterized control antigens (CSP-Plasmodium falciparum, M1 and NP Influenza A virus, core protein-Hepatitis B virus, and PSTA1-Mycobacterium tuberculosis). In order to determine an optimal set of epitopes among the highest scoring predicted epitopes, the OptiTope tool was employed for populations susceptible to cutaneous leishmaniasis. The epitope (127SLWSLLAGV) from antigen number 1, found to bind with the most prevalent allele HLA-A*0201 (25% frequency in Southwest Asia), was predicted as most immunogenic for all the target populations. Thus, our study reasserts the potential of genome-wide screening of pathogen antigens and epitopes, for identification of promising vaccine candidates. PMID- 26681958 TI - How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart? AB - Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question. PMID- 26681960 TI - Possible Mechanism of Action of the Antiallergic Effect of an Aqueous Extract of Heliotropium indicum L. in Ovalbumin-Induced Allergic Conjunctivitis. AB - Heliotropium indicum is used traditionally as a remedy for conjunctivitis in Ghana. This study therefore evaluated the antiallergic potential of an aqueous whole plant extract of Heliotropium indicum (HIE) in ovalbumin-induced allergic conjunctivitis and attempted to predict its mode of action. Clinical scores for allergic conjunctivitis induced by intraperitoneal ovalbumin sensitization (100 : 10 MUg OVA/Al(OH)3 in phosphate-buffered saline [PBS]) and topical conjunctival challenge (1.5 mg OVA in 10 MUL PBS) in Dunkin-Hartley guinea pigs were estimated after a week's daily treatment with 30-300 mg kg(-1) HIE, 30 mg kg(-1) prednisolone, 10 mg kg(-1) chlorpheniramine, or 10 mL kg(-1) PBS. Ovalbumin specific IgG and IgE and total IgE in serum were estimated using Enzyme-Linked Immunosorbent Assay. Histopathological assessment of the exenterated conjunctivae was also performed. The 30 and 300 mg kg(-1) HIE treatment resulted in a significantly (p <= 0.001) low clinical score of allergic conjunctivitis. Ovalbumin-specific IgG and IgE as well as total serum IgE also decreased significantly (p <= 0.01-0.001). The conjunctival tissue in HIE treated guinea pigs had mild mononuclear infiltration compared to the PBS-treated ones, which had intense conjunctival tissue inflammatory infiltration. HIE exhibited antiallergic effect possibly by immunomodulation or immunosuppression. PMID- 26681961 TI - ZnO-PLLA nanofiber nanocomposite for continuous flow mode purification of water from Cr(VI). AB - Nanomaterials of ZnO-PLLA nanofibers have been used for the adsorption of Cr(VI) as a prime step for the purification of water. The fabrication and application of the flexible ZnO-PLLA nanofiber nanocomposite as functional materials in this well-developed architecture have been achieved by growing ZnO nanorod arrays by chemical bath deposition on synthesized electrospun poly-L-lactide nanofibers. The nanocomposite material has been tested for the removal and regeneration of Cr(IV) in aqueous solution under a "continuous flow mode" by studying the effects of pH, contact time, and desorption steps. The adsorption of Cr(VI) species in solution was greatly dependent upon pH. SEM micrographs confirmed the successful fabrication of the ZnO-PLLA nanofiber nanocomposite. The adsorption and desorption of Cr(VI) species were more likely due to the electrostatic interaction between ZnO and Cr(VI) ions as a function of pH. The adsorption and desorption experiments utilizing the ZnO-PLLA nanofiber nanocomposite have appeared to be an effective nanocomposite in the removal and regeneration of Cr(VI) species. PMID- 26681962 TI - Metals exposures of residents living near the Akaki River in Addis Ababa, Ethiopia: a cross-sectional study. AB - BACKGROUND: The Akaki River in Ethiopia has been found to contain elevated levels of several metals. Our objectives were to characterize metals exposures of residents living near the Akaki River and to assess metal levels in their drinking water. METHODS: In 2011, we conducted a cross-sectional study of 101 households in Akaki-Kality subcity (near the Akaki River) and 50 households in Yeka subcity (distant to the Akaki River). One willing adult in each household provided urine, blood, and drinking water sample. RESULTS: Urinary molybdenum (p < 0.001), tungsten (p < 0.001), lead (p < 0.001), uranium (p < 0.001), and mercury (p = 0.049) were higher in Akaki-Kality participants compared to Yeka participants. Participants in both subcities had low urinary iodine; 45% met the World Health Organization (WHO) classification for being at risk of moderate iodine deficiency. In Yeka, 47% of households exceeded the WHO aesthetic-based reference value for manganese; in Akaki-Kality, only 2% of households exceeded this value (p < 0.001). There was no correlation between metals levels in water samples and clinical specimens. CONCLUSIONS: Most of the exposures found during this investigation seem unlikely to cause acute health effects based on known toxic thresholds. However, toxicity data for many of these metals are very limited. PMID- 26681963 TI - Neuroprotective Effect of Xueshuantong for Injection (Lyophilized) in Transient and Permanent Rat Cerebral Ischemia Model. AB - Xueshuantong for Injection (Lyophilized) (XST), a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk.), is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx) 6-toll-like receptor (TLR) 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO) induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1beta (IL 1beta), IL-17, IL-23p19, tumor necrosis factor-alpha (TNFalpha), and inducible nitric oxide synthase (iNOS) in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx) 6-toll-like receptor (TLR) 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats' weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway. PMID- 26681964 TI - The Activation of Nrf2 and Its Downstream Regulated Genes Mediates the Antioxidative Activities of Xueshuan Xinmaining Tablet in Human Umbilical Vein Endothelial Cells. AB - Epidemiological studies have verified the critical role that antioxidative stress plays in protecting vascular endothelial cells. The aims of the present study were to investigate the antioxidative activities and differential regulation of nuclear erythroid-related factor 2- (Nrf2-) mediated gene expression by Xueshuan Xinmaining Tablet (XXT), a traditional Chinese medicine with the effect of treating cardiovascular diseases. The antioxidative activities of XXT were investigated using quantitative real-time PCR (qPCR), a PCR array, and western blotting. Our results indicated that XXT exhibited potent antioxidative activities by suppressing the levels of hydrogen peroxide- (H2O2-) induced reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs). We were also conscious of strong Nrf2-mediated antioxidant induction. XXT enhanced the expressions of Keap1, Nrf2, and Nrf2-mediated genes, such as glutamate-cysteine ligase modifier subunit (GCLM), NAD(P)H: quinine oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutathione peroxidase (GPX) in HUVECs. In summary, XXT strongly activated Nrf2 and its downstream regulated genes, which may contribute to the antioxidative and vascular endothelial cell protective activities of XXT. PMID- 26681966 TI - Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis. AB - Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited. Complementary and alternative medicines represent exciting adjunctive therapies. In this study, we ascertained the beneficial and adverse effects of Chinese herbal medicine (CHM) in combination with conventional therapy for inoperable pancreatic cancer by using meta-analysis methods for controlled clinical trials. We extracted data for studies searched from six electronic databases that were searched and also assessed the methodological quality of the included studies. We evaluated the following outcome measures: 6-month and 1-year survival rate, objective response rate, disease control rate, quality of life, and adverse effects. The final analysis showed CHM is a promising strategy as an adjunctive therapy to treat advanced or inoperable pancreatic cancer and that CHM in combination with conventional therapy is a promising strategy for resistant disease. However, convincing evidence must be obtained and confirmed by high-quality trials in future studies. PMID- 26681965 TI - Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products. AB - Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish based assays for antidiabetic compounds in natural products-based laboratories. PMID- 26681967 TI - Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca(2+)-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo. AB - The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications. PMID- 26681968 TI - Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5 HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice. AB - The traditional Japanese medicine yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of yokukansan on a 5 HT1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with yokukansan. Thereafter, the density and affinity of 5-HT1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8 OH-DPAT; a 5-HT1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1A receptor density or affinity. However, yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that yokukansan increases 5-HT1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects. PMID- 26681969 TI - Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway. AB - Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 MUM). The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC 1 staining, and Hoechst/PI double staining (all p < 0.01). Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (p < 0.01). Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway. PMID- 26681970 TI - The Composition, Antioxidant and Antibacterial Activities of Cold-Pressed and Distilled Essential Oils of Citrus paradisi and Citrus grandis (L.) Osbeck. AB - The chemical composition and functional activities of cold-pressed and water distilled peel essential oils of Citrus paradisi (C. paradisi) and Citrus grandis (L.) Osbeck (C. grandis) were investigated in present study. Yields of cold pressed oils were much higher than those of distilled oils. Limonene was the primary ingredient of essential oils of C. paradisi (cold 92.83%; distilled 96.06%) and C. grandis (cold 32.63%; distilled 55.74%). In addition, C. grandis oils obtained were rich in oxygenated or nitrogenated compounds which may be involved in reducing cardiovascular diseases or enhancing sleep effectiveness. The order of free radical scavenging activities of 4 citrus oils was distilled C. paradisi oil > cold-pressed C. paradisi oil > distilled C. grandis oil > cold pressed C. grandis oil. Cold-pressed C. grandis oil exhibited the lowest activity in all antioxidative assays. The order of antimicrobial activities of 4 citrus oils was distilled C. grandis oil, cold-pressed C. paradisi oil > distilled C. paradisi oil > cold-pressed C. paradisi oil. Surprisingly, distilled C. grandis oil exhibited better antimicrobial activities than distilled C. paradisi oil, especially against Escherichia coli and Salmonella enterica subsp. The results also indicated that the antimicrobial activities of essential oils may not relate to their antioxidative activities. PMID- 26681971 TI - Study on the Difference of BIS/BAS Scale between Sasang Types. AB - Introduction. The purpose of this study was to examine the differences in temperament between So-Yang (SY) and So-Eum (SE) Sasang types using Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale to elucidate the biopsychological mechanism underlying the Sasang typology, a traditional Korean personalized medicine. Methods. 248 university students were categorized into three Sasang types, and series of t-tests were conducted, separately for male and female participants, to examine the difference of Behavioral Inhibition System (BIS), Behavioral Activation System (BAS), BAS-Drive (BAS-D), BAS-Fun Seeking (BAS-FS), and BAS-Reward Responsiveness (BAS-RR) scores between SY and SE Sasang types. Results. There were significant differences between Sasang types in the BIS/BAS subscales with consideration of gender. In male participants, BAS-total score of SY type (39.75 +/- 4.56) was significantly (t = 2.462, p = 0.016) higher than that of SE type (36.68 +/- 4.97). On the other hand, in female participants, BIS score of SY type (20.10 +/- 4.01) was significantly (t = -2.097, p = 0.039) lower than that of SE type (21.83 +/- 3.91). Discussion. The current study suggested relationship between Sasang typology and Behavior Inhibition and Activation Systems and showed significant differences in BIS/BAS scale between SY and SE Sasang types. Further studies on biological base of Sasang typology are needed. PMID- 26681973 TI - Collagenous spherulosis: An interesting cytological finding in breast lesion. AB - Collagenous spherulosis (CS) is a rare and interesting entity associated with benign breast lesions. CS is an incidental finding picked up only on 0.2% of cytology specimen. Typically cytologically of CS of breast consists of central spherical hyaline spherule surrounded by myoepithelial cells. The central hyaline spherule has been found to be basement membrane material histochemically and immunohistochemically. The importance of recognizing CS of breast lies in the fact that similar hyaline globules can occur in adenoid cystic carcinoma of the breast (ACCB). The two lesions need to be differentiated on cytology failing which inappropriate treatment can be given for either of the two lesions. We present here a case of CS associated with benign breast lesion and a case of ACCB to describe their cytological features and key points to differentiate them cytologically. PMID- 26681972 TI - RACE AS LIVED EXPERIENCE: The Impact of Multi-Dimensional Measures of Race/Ethnicity on the Self-Reported Health Status of Latinos. AB - A growing body of social science research has sought to conceptualize race as a multidimensional concept in which context, societal relations, and institutional dynamics are key components. Utilizing a specially designed survey, we develop and use multiple measures of race (skin color, ascribed race, and discrimination experiences) to capture race as "lived experience" and assess their impact on Latinos' self-rated health status. We model these measures of race as a lived experience to test the explanatory power of race, both independently and as an integrated scale with categorical regression, scaling, and dimensional analyses. Our analyses show that our multiple measures of race have significant and negative effects on Latinos' self-reported health. Skin color is a dominant factor that impacts self-reported health both directly and indirectly. We then advocate for the utilization of multiple measures of race, adding to those used in our analysis, and their application to other health and social outcomes. Our analysis provides important contributions across a wide range of health, illness, social, and political outcomes for communities of color. PMID- 26681974 TI - Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. AB - To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM. PMID- 26681975 TI - Pitfall in immunohistochemical staining for thyroglobulin in case of thyroid metastasis from lung carcinoma. PMID- 26681976 TI - Use of alcohol and drugs by employees in selected business areas in Norway: a study using oral fluid testing and questionnaires. AB - BACKGROUND: Alcohol or drug use and associated hangover may reduce workplace safety and productivity and also cause sickness absence. The aims of this study were to examine (i) the use of alcohol and drugs, and (ii) reduced efficiency at work and absence due to such use among employees. METHODS: Forty-four companies were invited; half of them agreed to participate. Employees filled in a questionnaire and provided a sample of oral fluid, which was analysed for alcohol, 12 psychoactive medicinal drugs and 6 illicit drugs. Participation was voluntary and anonymous. RESULTS: Two thousand four hundred thirty-seven employees in eight business areas agreed to participate (92 % of those invited). By combining questionnaires and oral fluid testing, we found that 5.2 % had used psychoactive medication during the last couple of days, 1.4 % had used illicit drugs, 17.0 % had used alcohol during the last 24 h but only one person (0.04 %) was positive for alcohol in oral fluid. About 25 % reported reduced efficiency at work, and 5 % reported absence from work due to alcohol use during the past 12 months. The use of illicit drugs and binge drinking resulting in reduced efficiency and absence was most common among restaurant and bar workers and more common among men than women, whereas use of psychoactive medication was most common among healthcare, transportation and storage workers. CONCLUSION: Impairment at work due to alcohol or drugs was rare, whereas reduced efficiency due to drinking was reported by a fairly large proportion. There were marked differences between some business areas, and across gender. PMID- 26681977 TI - Voice Disorder Classification Based on Multitaper Mel Frequency Cepstral Coefficients Features. AB - The Mel Frequency Cepstral Coefficients (MFCCs) are widely used in order to extract essential information from a voice signal and became a popular feature extractor used in audio processing. However, MFCC features are usually calculated from a single window (taper) characterized by large variance. This study shows investigations on reducing variance for the classification of two different voice qualities (normal voice and disordered voice) using multitaper MFCC features. We also compare their performance by newly proposed windowing techniques and conventional single-taper technique. The results demonstrate that adapted weighted Thomson multitaper method could distinguish between normal voice and disordered voice better than the results done by the conventional single-taper (Hamming window) technique and two newly proposed windowing methods. The multitaper MFCC features may be helpful in identifying voices at risk for a real pathology that has to be proven later. PMID- 26681978 TI - Gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis. AB - BACKGROUND: Adolescent Idiopathic Scoliosis is the most common type of spinal deformity, and whilst the isk of progression appears to be biomechanically mediated (larger deformities are more likely to progress), the detailed biomechanical mechanisms driving progression are not well understood. Gravitational forces in the upright position are the primary sustained loads experienced by the spine. In scoliosis they are asymmetrical, generating moments about the spinal joints which may promote asymmetrical growth and deformity progression. Using 3D imaging modalities to estimate segmental torso masses allows the gravitational loading on the scoliotic spine to be determined. The resulting distribution of joint moments aids understanding of the mechanics of scoliosis progression. METHODS: Existing low-dose CT scans were used to estimate torso segment masses and joint moments for 20 female scoliosis patients. Intervertebral joint moments at each vertebral level were found by summing the moments of each of the torso segment masses above the required joint. RESULTS: The patients' mean age was 15.3 years (SD 2.3; range 11.9-22.3 years); mean thoracic major Cobb angle 52( degrees ) (SD 5.9( degrees ); range 42-63( degrees )) and mean weight 57.5 kg (SD 11.5 kg; range 41-84.7 kg). Joint moments of up to 7 Nm were estimated at the apical level. No significant correlation was found between the patients' major Cobb angles and apical joint moments. CONCLUSIONS: Patients with larger Cobb angles do not necessarily have higher joint moments, and curve shape is an important determinant of joint moment distribution. These findings may help to explain the variations in progression between individual patients. This study suggests that substantial corrective forces are required of either internal instrumentation or orthoses to effectively counter the gravity induced moments acting to deform the spinal joints of idiopathic scoliosis patients. PMID- 26681979 TI - Putting Families Into Place: Using Neighborhood-Effects Research and Activity Spaces to Understand Families. AB - Neighborhood is an important context in which individuals and families are embedded. Yet family studies researchers have been relatively slow to incorporate spatial approaches into family science. Although limited theoretical and methodological attention has been devoted to families in neighborhood-effects research, family scholars can contribute greatly to theories about neighborhood effects, and neighborhood-effects research can help move the field of family studies forward. This article reviews the theories, applications, and limitations of research on neighborhood effects and discusses how family studies can benefit from incorporating a spatial perspective from neighborhood-effects research. I then present an innovative methodology-referred to as activity spaces-emerging in neighborhood-effects research, and I discuss how this approach can be used to better understand the complexity and heterogeneity of families. Last, I highlight ways to incorporate space into family studies by "putting families into place." PMID- 26681980 TI - Primary care: a fading jewel in the NHS crown. AB - When Jeremy Hunt, the Secretary for State for Health in England, presented his 'New Deal for General Practice' in June 2015, he described general practice as the jewel in the crown of the NHS. Many general practitioners (GPs) though will not be reassured by his statement. Despite Jeremy Hunt's words of support, the future for GPs, their teams and their patients looks very uncertain. It is hard to see how planned levels of funding for the NHS in England can sustain a readily accessible, high-quality primary care service. It seems likely that primary care in England will increasingly be delivered by non-medical professionals, such as pharmacists, nurses, physician assistants and health care assistants. The acceptability to patients - and the impact on quality of care, patient outcomes and the other parts of the NHS - of this model are all unknown. An alternative scenario is that we gradually move to a 'two-tier' primary care system with those patients who can afford to do so paying to see a medically qualified GP. PMID- 26681981 TI - Atypical leg symptoms: does routine measurement of the ankle brachial pressure index (ABPI) in primary care benefit patients? AB - Background : Managing patients with atypical leg symptoms in primary care can be problematic. Determining the ankle brachial pressure index (ABPI) may be readily performed to help diagnose peripheral arterial disease, but is often omitted where signs and symptoms are unclear. Question: Does routine measurement of ABPI in patients with atypical leg symptoms aid management increase satisfaction and safely reduce hospital referral? Methodology: Patients with atypical leg symptoms but no skin changes or neurological symptoms underwent clinical review and Doppler ABPI measurement (suspicious finding <= 1.0). Testing was performed by the same doctor (study period: 30 months). Patient outcomes were determined from practice records, hospital letters and a telephone survey. Results : The study comprised 35 consecutive patients (males: N = 15), mean age 64 years (range: 39 88). Presentation included pain, cold feet, cramps, irritation and concerns regarding circulation. Prior to ABPI measurement, referral was considered necessary in 10, not required in 22 and unclear in 3. ABPI changed the referral decision in 10 (29%) and confirmed the decision in 25 (71%). During the study, 10 (29%) patients were referred (9 vascular, 1 neurology). Amongst the vascular referrals, significant peripheral arterial disease has been confirmed in six patients. A further two patients are under review and one did not attend. To date, lack of referral in patients with atypical leg symptoms but a normal ABPI has not increased morbidity. Current status was assessed by telephone review in 16/35 (46% contact rate; mean 18 months, range 2-28). Fifteen patients (94%) appreciated that their symptoms had been quickly and conveniently assessed, 8/11 (73%) with a normal ABPI were reassured by their result and in 8/11 symptoms have resolved. Discussion/Conclusion: APBI conveniently aids management of atypical leg symptoms by detecting unexpected peripheral arterial disease, avoids /confirms the need for referral, reassures patients and guides reassessment. This study suggests ABPI should be used more widely. PMID- 26681982 TI - Balance between climate change mitigation benefits and land use impacts of bioenergy: conservation implications for European birds. AB - Both climate change and habitat modification exert serious pressure on biodiversity. Although climate change mitigation has been identified as an important strategy for biodiversity conservation, bioenergy remains a controversial mitigation action due to its potential negative ecological and socio-economic impacts which arise through habitat modification by land-use change. While the debate continues, the separate or simultaneous impacts of both climate change and bioenergy on biodiversity have not yet been compared. We assess projected range shifts of 156 European bird species by 2050 under two alternative climate change trajectories: a baseline scenario, where the global mean temperature increases by 4 degrees C by the end of the century, and a 2 degrees scenario, where global concerted effort limits the temperature increase to below 2 degrees C. For the latter scenario, we also quantify the pressure exerted by increased cultivation of energy biomass as modelled by IMAGE2.4, an integrated land-use model. The global bioenergy use in this scenario is in the lower end of the range of previously estimated sustainable potential. Under the assumptions of these scenarios, we find that the magnitude of range shifts due to climate change is far greater than the impact of land conversion to woody bioenergy plantations within the European Union, and that mitigation of climate change reduces the exposure experienced by species. However, we identified potential for local conservation conflict between priority areas for conservation and bioenergy production. These conflicts must be addressed by strict bioenergy sustainability criteria that acknowledge biodiversity conservation needs beyond existing protected areas and apply also to biomass imported from outside the European Union. PMID- 26681983 TI - Ultrasound Targeted Microbubble Destruction-Mediated Delivery of a Transcription Factor Decoy Inhibits STAT3 Signaling and Tumor Growth. AB - Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many cancers where it acts to promote tumor progression. A STAT3 specific transcription factor decoy has been developed to suppress STAT3 downstream signaling, but a delivery strategy is needed to improve clinical translation. Ultrasound-targeted microbubble destruction (UTMD) has been shown to enhance image-guided local delivery of molecular therapeutics to a target site. The objective of this study was to deliver STAT3 decoy to squamous cell carcinoma (SCC) tumors using UTMD to disrupt STAT3 signaling and inhibit tumor growth. Studies performed demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles inhibited STAT3 signaling in SCC cells in vitro. Studies performed in vivo demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles induced significant tumor growth inhibition (31-51% reduced tumor volume vs. controls, p < 0.05) in mice bearing SCC tumors. Furthermore, expression of STAT3 downstream target genes (Bcl-xL and cyclin D1) was significantly reduced (34-39%, p < 0.05) in tumors receiving UTMD treatment with STAT3 decoy-loaded microbubbles compared to controls. In addition, the quantity of radiolabeled STAT3 decoy detected in tumors eight hours after treatment was significantly higher with UTMD treatment compared to controls (70-150%, p < 0.05). This study demonstrates that UTMD can increase delivery of a transcription factor decoy to tumors in vivo and that the decoy can inhibit STAT3 signaling and tumor growth. These results suggest that UTMD treatment holds potential for clinical use to increase the concentration of a transcription factor signaling inhibitor in the tumor. PMID- 26681985 TI - Echogenic Glycol Chitosan Nanoparticles for Ultrasound-Triggered Cancer Theranostics. AB - Theranostic nanoparticles hold great promise for simultaneous diagnosis of diseases, targeted drug delivery with minimal toxicity, and monitoring of therapeutic efficacy. However, one of the current challenges in developing theranostic nanoparticles is enhancing the tumor-specific targeting of both imaging probes and anticancer agents. Herein, we report the development of tumor homing echogenic glycol chitosan-based nanoparticles (Echo-CNPs) that concurrently execute cancer-targeted ultrasound (US) imaging and US-triggered drug delivery. To construct this novel Echo-CNPs, an anticancer drug and bioinert perfluoropentane (PFP), a US gas precursor, were simultaneously encapsulated into glycol chitosan nanoparticles using the oil in water (O/W) emulsion method. The resulting Echo-CNPs had a nano-sized particle structure, composing of hydrophobic anticancer drug/PFP inner cores and a hydrophilic glycol chitosan polymer outer shell. The Echo-CNPs had a favorable hydrodynamic size of 432 nm, which is entirely different from the micro-sized core-empty conventional microbubbles (1 10 MUm). Furthermore, Echo-CNPs showed the prolonged echogenicity via the sustained microbubble formation process of liquid-phase PFP at the body temperature and they also presented a US-triggered drug release profile through the external US irradiation. Interestingly, Echo-CNPs exhibited significantly increased tumor-homing ability with lower non-specific uptake by other tissues in tumor-bearing mice through the nanoparticle's enhanced permeation and retention (EPR) effect. Conclusively, theranostic Echo-CNPs are highly useful for simultaneous cancer-targeting US imaging and US-triggered delivery in cancer theranostics. PMID- 26681986 TI - High Efficiency Molecular Delivery with Sequential Low-Energy Sonoporation Bursts. AB - Microbubbles interact with ultrasound to induce transient microscopic pores in the cellular plasma membrane in a highly localized thermo-mechanical process called sonoporation. Theranostic applications of in vitro sonoporation include molecular delivery (e.g., transfection, drug loading and cell labeling), as well as molecular extraction for measuring intracellular biomarkers, such as proteins and mRNA. Prior research focusing mainly on the effects of acoustic forcing with polydisperse microbubbles has identified a "soft limit" of sonoporation efficiency at 50% when including dead and lysed cells. We show here that this limit can be exceeded with the judicious use of monodisperse microbubbles driven by a physiotherapy device (1.0 MHz, 2.0 W/cm(2), 10% duty cycle). We first examined the effects of microbubble size and found that small-diameter microbubbles (2 um) deliver more instantaneous power than larger microbubbles (4 & 6 um). However, owing to rapid fragmentation and a short half-life (0.7 s for 2 um; 13.3 s for 6 um), they also deliver less energy over the sonoporation time. This translates to a higher ratio of FITC-dextran (70 kDa) uptake to cell death/lysis (4:1 for 2 um; 1:2 for 6 um) in suspended HeLa cells after a single sonoporation. Sequential sonoporations (up to four) were consequently employed to increase molecular delivery. Peak uptake was found to be 66.1 +/- 1.2% (n=3) after two sonoporations when properly accounting for cell lysis (7.0 +/- 5.6%) and death (17.9 +/- 2.0%), thus overcoming the previously reported soft limit. Substitution of TRITC-dextran (70 kDa) on the second sonoporation confirmed the effects were multiplicative. Overall, this study demonstrates the possibility of utilizing monodisperse small-diameter microbubbles as a means to achieve multiple low-energy sonoporation bursts for efficient in vitro cellular uptake and sequential molecular delivery. PMID- 26681984 TI - PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status. AB - Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided. PMID- 26681987 TI - Phototheranostic Porphyrin Nanoparticles Enable Visualization and Targeted Treatment of Head and Neck Cancer in Clinically Relevant Models. AB - Head and neck cancer is the fifth most common type of cancer worldwide and remains challenging for effective treatment due to the proximity to critical anatomical structures in the head and neck region, which increases the probability of toxicity from surgery and radiotherapy, and therefore emphasizes the importance of maximizing the targeted ablation. We have assessed the effectiveness of porphysome nanoparticles to enhance fluorescence and photoacoustic imaging of head and neck tumors in rabbit and hamster models. In addition, we evaluated the effectiveness of this agent for localized photothermal ablative therapy of head and neck tumors. We have demonstrated that porphysomes not only enabled fluorescence and photoacoustic imaging of buccal and tongue carcinomas, but also allowed for complete targeted ablation of these tumors. The supremacy of porphysome-enabled photothermal therapy over surgery to completely eradicate primary tumors and metastatic regional lymph node while sparing the adjacent critical structures' function has been demonstrated for the first time. This study represents a novel breakthrough that has the potential to revolutionize our approach to tumor diagnosis and treatment in head and neck cancer and beyond. PMID- 26681988 TI - Noninvasive Dynamic Imaging of Tumor Early Response to Nanoparticle-mediated Photothermal Therapy. AB - In spite of rapidly increasing interest in the use of nanoparticle-mediated photothermal therapy (PTT) for treatment of different types of tumors, very little is known on early treatment-related changes in tumor response. Using graphene oxide (GO) as a model nanoparticle (NP), in this study, we tracked the changes in tumors after GO NP-mediated PTT by magnetic resonance imaging (MRI) and quantitatively identified MRI multiple parameters to assess the dynamic changes of MRI signal in tumor at different heating levels and duration. We found a time- and temperature-dependent dynamic change of the MRI signal intensity in intratumor microenvironment prior to any morphological change of tumor, mainly due to quick and effective eradication of tumor blood vessels. Based on the distribution of GO particles, we also demonstrated that NP-medited PTT caused heterogeneous thermal injury of tumor. Overall, these new findings provide not only a clinical-related method for non-invasive early tracking, identifying, and monitoring treatment response of NP-mediated PTT but also show a new vision for better understanding mechanisms of NP-mediated PTT. PMID- 26681990 TI - Familial and Economic Influences on the Gender-Related Educational and Occupational Aspirations of Rural Adolescents. AB - Economic, occupational, and social shifts in rural economies have influenced nuanced changes in the educational and occupational aspirations of rural adolescent women and men. However, there is limited contemporary research that examines the aspirations of rural adolescents at the beginning of the 21st century. Drawing on a sample of 8,756 rural adolescents in the United States, we examine how familial, geographic, and economic variables influence gender-related differences in educational and occupational aspirations. Findings revealed significant gender differences, favoring girls, in youth's educational aspirations, occupational aspirations, and aspirations for nontraditional careers. Results highlight the importance of contextual variables such as parental expectations, family income, and motivation variables in predicting gender-related aspirations of rural youth. PMID- 26681991 TI - Optimizing Hybrid Metrology: Rigorous Implementation of Bayesian and Combined Regression. AB - Hybrid metrology, e.g., the combination of several measurement techniques to determine critical dimensions, is an increasingly important approach to meet the needs of the semiconductor industry. A proper use of hybrid metrology may yield not only more reliable estimates for the quantitative characterization of 3-D structures but also a more realistic estimation of the corresponding uncertainties. Recent developments at the National Institute of Standards and Technology (NIST) feature the combination of optical critical dimension (OCD) measurements and scanning electron microscope (SEM) results. The hybrid methodology offers the potential to make measurements of essential 3-D attributes that may not be otherwise feasible. However, combining techniques gives rise to essential challenges in error analysis and comparing results from different instrument models, especially the effect of systematic and highly correlated errors in the measurement on the chi2 function that is minimized. Both hypothetical examples and measurement data are used to illustrate solutions to these challenges. PMID- 26681989 TI - EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model. AB - Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours. Importantly, silencing of survivin with this aptamer-siRNA chimera in cancer stem cell population led to the reversal of chemoresistance, such that combined treatment with low dose of doxorubicin inhibited stemness, eliminated cancer stem cells via apoptosis, suppressed tumour growth, and prolonged survival in mice bearing chemoresistant tumours. This strategy for in vivo cancer stem cell targeting has wide application for future effective silencing of anti-death genes and in fact any dysregulated genes involved in chemoresistance and tumour relapse. PMID- 26681992 TI - Reuse, Recycle, Reweigh: Combating Influenza through Efficient Sequential Bayesian Computation for Massive Data. AB - Massive datasets in the gigabyte and terabyte range combined with the availability of increasingly sophisticated statistical tools yield analyses at the boundary of what is computationally feasible. Compromising in the face of this computational burden by partitioning the dataset into more tractable sizes results in stratified analyses, removed from the context that justified the initial data collection. In a Bayesian framework, these stratified analyses generate intermediate realizations, often compared using point estimates that fail to account for the variability within and correlation between the distributions these realizations approximate. However, although the initial concession to stratify generally precludes the more sensible analysis using a single joint hierarchical model, we can circumvent this outcome and capitalize on the intermediate realizations by extending the dynamic iterative reweighting MCMC algorithm. In doing so, we reuse the available realizations by reweighting them with importance weights, recycling them into a now tractable joint hierarchical model. We apply this technique to intermediate realizations generated from stratified analyses of 687 influenza A genomes spanning 13 years allowing us to revisit hypotheses regarding the evolutionary history of influenza within a hierarchical statistical framework. PMID- 26681993 TI - Disentangling Disadvantage: Can We Distinguish Good Teaching from Classroom Composition? AB - This paper investigates the use of teacher value-added estimates to assess the distribution of effective teaching across students of varying socioeconomic disadvantage in the presence of classroom composition effects. We examine, via simulations, how accurately commonly-used teacher-value added estimators recover the rank correlation between true and estimated teacher effects and a parameter representing the distribution of effective teaching. We consider various scenarios of teacher assignment, within-teacher variability in classroom composition, importance of classroom composition effects, and presence of student unobserved heterogeneity. No single model recovers without bias estimates of the distribution parameter in all the scenarios we consider. Models that rank teacher effectiveness most accurately do not necessarily recover distribution parameter estimates with less bias. Since true teacher sorting in real data is seldom known, we recommend that analysts incorporate contextual information into their decisions about model choice and we offer some guidance on how to do so. PMID- 26681994 TI - Nasal Tip Reconstruction Using Integra Bilayer Wound Matrix: An Alternative to the Forehead Flap. AB - Large defects of the nasal tip with exposure of the underlying cartilage pose a significant reconstructive challenge to the plastic surgeon. OBJECTIVE: This article presents a case of a large nasal tip defect following basal cell excision that was successfully treated with Integra bilayer wound matrix and skin grafting. METHODS: Following tumor excision, meshed Integra bilayer wound matrix was placed over the exposed nasal tip cartilage. After 4 weeks, the silicone layer was removed and a full-thickness graft placed on the nasal tip. RESULTS: This reconstruction resulted in the restoration of patient's nasal tip with good contour and color match without the need for a forehead flap. CONCLUSION: This demonstrates the reconstructive potential of this modality in patients who are not candidates for reconstruction with a forehead flap. PMID- 26681995 TI - An extended Tajima's D neutrality test incorporating SNP calling and imputation uncertainties. AB - To identify evolutionary events from the footprints left in the patterns of genetic variation in a population, people use many statistical frameworks, including neutrality tests. In datasets from current high throughput sequencing and genotyping platforms, it is common to have missing data and low-confidence SNP calls at many segregating sites. However, the traditional statistical framework for neutrality tests does not allow for these possibilities; therefore the usual way of treating missing data is to ignore segregating sites with missing/low confidence calls, regardless of the good SNP calls at these sites in other individuals. In this work, we propose a modified neutrality test, Extended Tajima's D, which incorporates missing data and SNP-calling uncertainties. Because we do not specify any particular error-generating mechanism, this approach is robust and widely applicable. Simulations show that in most cases the power of the new test is better than the original Tajima's D, given the same type I error. Applications to real data show that it detects fewer outliers associated with low quality data. PMID- 26681996 TI - Asthma education material for children and their families; a global survey of current resources. AB - One of the keys to high quality paediatric asthma management is the provision of age appropriate information regarding the disease and its management. In order to determine whether the generation of a minimum dataset of information which can be translated into a wide range of languages might be used to assist children and their parents around the world, we undertook a survey of national Member Societies of the World Allergy Organization (WAO) to determine what educational material on asthma for children and their families already exists. A questionnaire was developed using Survey Monkey and distributed in 2014 to 263 representatives of the WAO member Societies from 95 countries. Thirty-three replies were received from thirty-one countries. The survey highlighted a considerable disparity in availability of material among the responding countries, with some countries reporting that information was freely available in hard copy and online and others reporting a lack of suitable material locally. The results highlight the need to develop a core set of simple, clear and consistent age appropriate information that can be easily translated and delivered in a cultural and educationally effective format. PMID- 26681997 TI - Debates in allergy medicine: food intolerance does exist. AB - BACKGROUND: Health care professionals and patients mix and mingle (hyper)sensitivity, allergy and intolerance. The consequences are discrepancies which result in confusion. The following is a very personal point of view, intended to start a debate to come to consensus. OBJECTIVES: We aimed to clarify the proposed terminology for the primary health care professional from the point of view of the pediatric gastroenterologist. RESULTS: Many patients present with symptoms "related to food ingestion". We propose to use this wording if no underlying mechanism can be identified. Intolerance should be restricted to carbohydrate malabsorption causing symptoms. Allergy is restricted to IgE mediated allergy and non-IgE manifestations that can only be explained through an immune mediated mechanism, such as food induced atopic dermatitis and allergic colitis with blood in the stools. Unfortunately, primary heath care physicians have no diagnostic tools for non-IgE mediated allergy. A positive challenge test is a proof of a food-induced symptom, but does not proof that the immune system is involved. (Hyper)sensitivity suggests immune mediated mechanisms and should therefore not be used. The pathophysiologic mechanism of many food-related symptoms is unclear. The same symptom can be caused by allergy or be considered functional, such as infantile colic, gastro-esophageal reflux and constipation related to cow's milk ingestion in infants. In fact, "functional" is used if the pathophysiologic mechanism causing the symptom cannot be explained. Since the long term outcome of "allergy" differs substantially from "functional symptom", allergy should not be used inappropriate. CONCLUSION: "Food related symptom" should be used in each patient in which the pathophysiologic mechanism is not clear. Intolerance means a carbohydrate malabsorption that causes symptoms. Allergy should be used when the immune system is involved. PMID- 26681998 TI - Debates in allergy medicine: food intolerance does not exist. AB - BACKGROUND: The term "intolerance" is not mentioned in the World Allergy Organization (WAO) document on allergy nomenclature. "Intolerance" has been used to describe some non-immunological diseases. However, pediatric gastroenterologists mix allergy and intolerance, e.g. by using the term "cow's milk protein allergy/intolerance (CMPA/I)", lumping together all types of mechanisms for not tolerating cow's milk. The basis for this mix is the fact that double-blind oral food challenges are time-consuming and expensive. Therefore, cow's milk exclusion and reintroduction is proposed to be used in primary care for the diagnosis of CMPA in children with common gastrointestinal (GI) problems such as colic and constipation. This may lead to a widespread use of hypoallergenic formulas in children without proven CMPA. In lay language, intolerance describes "not tolerating". OBJECTIVE: To discuss the reasons why the term "intolerance" should not be used in the area of allergy. RESULTS: Presently, intolerance is not part of the allergy nomenclature. It is used by lay persons to describe "not tolerating". Pediatricians use intolerance to describe non immunological hypersensitivity such as lactose intolerance which is acceptable. However, using the mixed term CMPA/I describing a variety of gastrointestinal symptoms in children, should be avoided. The WAO Nomenclature does not clearly distinguish between non-IgE-mediated allergy and non-allergic hypersensitivity. CONCLUSION: The term "intolerance" should not be used within the area of allergy. Intolerance should be better defined and the term restricted to some non immunological/non-allergic diseases and not mixed with allergy, e.g. by using the term CMPA/I. A revision of the WAO nomenclature is proposed. PMID- 26681999 TI - Urticaria as initial finding of a patient with carcinoid tumor. AB - BACKGROUND: Typical carcinoid syndrome is characterized by flushing, abdominal pain and diarrhea and occurs in <10 % of carcinoid tumor patients. Very rarely, initial signs include skin manifestations. Our purpose is to highlight cutaneous manifestations in the diagnosis and assessment of a patient with atypical manifestation of type I gastric carcinoid tumor. CASE PRESENTATION: A 50-year-old woman presented with anemia, chronic urticaria and angioedema. Urticaria was triggered principally by seafood and appeared in the first hour after. Urticaria Activity Score 7 was 24, and quality of life (CU-Q2oL) was 3.61. P. Laboratory findings showed anemia, diminished iron, ferritin, and vitamin B12, with increased gastrin and anti-parietal cell antibody levels. 15 gastric carcinoids 5 mm in diameter were observed in the greater curvature of the stomach during gastric endoscopy and confirmed by biopsy, suggesting that this patient had type I gastric carcinoids. Four additional tumors were found in the small intestine upon examination via video capsule. Endoscopic argon plasma therapy was performed. The patient experienced definitive improvement in quality of life and urticaria activity score. CONCLUSION: This patient, whose principal symptoms were anemia, urticaria and angioedema, was found to have atypical carcinoid syndrome, with tumors located in the stomach. Allergists, immunologists, internists and primary care physicians should consider the possibility of neuroendocrine malignancies, specifically type I carcinoid tumors, when evaluating patients with urticaria, and consider screening patients with chronic urticaria for elevated anti-parietal cell antibody levels. PMID- 26682000 TI - Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats. AB - Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFalpha and IL1alpha, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis. PMID- 26682002 TI - Histone Deacetylase Inhibitors Increase p27(Kip1) by Affecting Its Ubiquitin Dependent Degradation through Skp2 Downregulation. AB - Histone deacetylase inhibitors (HDACIs) represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress. In vitro, HDACIs induce different cellular responses including growth arrest, differentiation, and apoptosis. Here, we evaluated the effects of HDACIs on p27(Kip1), a key cyclin-dependent kinase inhibitor (CKI). We observed that HDACI dependent antiproliferative activity is associated with p27(Kip1) accumulation due to a reduced protein degradation. p27(Kip1) removal requires a preliminary ubiquitination step due to the Skp2-SCF E3 ligase complex. We demonstrated that HDACIs increase p27(Kip1) stability through downregulation of Skp2 protein levels. Skp2 decline is only partially due to a reduced Skp2 gene expression. Conversely, the protein decrease is more profound and enduring compared to the changes of Skp2 transcript. This argues for HDACIs effects on Skp2 protein posttranslational modifications and/or on its removal. In summary, we demonstrate that HDACIs increase p27(Kip1) by hampering its nuclear ubiquitination/degradation. The findings might be of relevance in the phenotypic effects of these compounds, including their anticancer and aging-modulating activities. PMID- 26682001 TI - Redox Modulating NRF2: A Potential Mediator of Cancer Stem Cell Resistance. AB - Tumors contain a distinct small subpopulation of cells that possess stem cell like characteristics. These cells have been called cancer stem cells (CSCs) and are thought to be responsible for anticancer drug resistance and tumor relapse after therapy. Emerging evidence indicates that CSCs share many properties, such as self-renewal and quiescence, with normal stem cells. In particular, CSCs and normal stem cells retain low levels of reactive oxygen species (ROS), which can contribute to stem cell maintenance and resistance to stressful tumor environments. Current literatures demonstrate that the activation of ataxia telangiectasia mutated (ATM) and forkhead box O3 (FoxO3) is associated with the maintenance of low ROS levels in normal stem cells such as hematopoietic stem cells. However, the importance of ROS signaling in CSC biology remains poorly understood. Recent studies demonstrate that nuclear factor-erythroid 2-related factor 2 (NRF2), a master regulator of the cellular antioxidant defense system, is involved in the maintenance of quiescence, survival, and stress resistance of CSCs. Here, we review the recent findings on the roles of NRF2 in maintenance of the redox state and multidrug resistance in CSCs, focusing on how NRF2-mediated ROS modulation influences the growth and resistance of CSCs. PMID- 26682003 TI - The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species. AB - Nrf2 (NF-E2-related factor 2) pathway and autophagy both can respond to oxidative stress to promote cancer cells to survive in the tumor microenvironment. We, therefore, explored the relevance between Nrf2 pathway and autophagy in pancreatic cancer cells upon stimulation of reactive oxygen species (ROS). Pancreatic cancer cells were cultured under controlled ROS stressing condition or basal condition. Different inhibitors were used to prevent autophagy at particular stages. Nrf2 siRNA was used to inhibit Nrf2 pathway activation. Ad mRFP-GFP-LC3 infection was used to monitor autophagic flux. The result shows that a small amount of exogenous hydrogen peroxide (H2O2) can significantly improve the level of intracellular ROS. Moreover, our findings indicate that ROS promotes the activation of both Nrf2 pathway and autophagy in pancreatic cancer cells. Moreover, our data demonstrate that suppression of autophagic activity at particular stages results in an increased promotion of Nrf2 pathway activation upon ROS stimulation. Furthermore, we found that silencing of Nrf2 promotes autophagy upon ROS stimulation. In addition, Nrf2 interference effectively promotes autophagic flux upon ROS stimulation. In summary, our findings suggest that Nrf2 pathway and autophagy have a negative interaction with each other upon ROS stimulation. PMID- 26682005 TI - Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats. AB - This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific alpha2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific alpha2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific alpha2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through alpha2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT. PMID- 26682004 TI - Dietary Restriction and Nutrient Balance in Aging. AB - Dietary regimens that favour reduced calorie intake delay aging and age associated diseases. New evidences revealed that nutritional balance of dietary components without food restriction increases lifespan. Particular nutrients as several nitrogen sources, proteins, amino acid, and ammonium are implicated in life and healthspan regulation in different model organisms from yeast to mammals. Aging and dietary restriction interact through partially overlapping mechanisms in the activation of the conserved nutrient-signalling pathways, mainly the insulin/insulin-like growth factor (IIS) and the Target Of Rapamycin (TOR). The specific nutrients of dietary regimens, their balance, and how they interact with different genes and pathways are currently being uncovered. Taking into account that dietary regimes can largely influence overall human health and changes in risk factors such as cholesterol level and blood pressure, these new findings are of great importance to fully comprehend the interplay between diet and humans health. PMID- 26682006 TI - Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging. AB - Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with beta-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS. PMID- 26682007 TI - Juglanthraquinone C Induces Intracellular ROS Increase and Apoptosis by Activating the Akt/Foxo Signal Pathway in HCC Cells. AB - Juglanthraquinone C (JC), a naturally occurring anthraquinone extracted from Juglans mandshurica, could induce apoptosis of cancer cells. This study aims to investigate the detailed cytotoxicity mechanism of JC in HepG2 and BEL-7402 cells. The Affymetrix HG-U133 Plus 2.0 arrays were first used to analyze the mRNA expression exposed to JC or DMSO in HepG2 cells. Consistent with the previous results, the data indicated that JC could induce apoptosis and hyperactivated Akt. The Western blot analysis further revealed that Akt, a well-known survival protein, was strongly activated in HepG2 and BEL-7402 cells. Furthermore, an obvious inhibitory effect on JC-induced apoptosis was observed when the Akt levels were decreased, while the overexpression of constitutively active mutant Akt greatly accelerated JC-induced apoptosis. The subsequent results suggested that JC treatment suppressed nuclear localization and increased phosphorylated levels of Foxo3a, and the overexpression of Foxo3a abrogated JC-induced apoptosis. Most importantly, the inactivation of Foxo3a induced by JC further led to an increase of intracellular ROS levels by suppressing ROS scavenging enzymes, and the antioxidant N-acetyl-L-cysteine and catalase successfully decreased JC induced apoptosis. Collectively, this study demonstrated that JC induced the apoptosis of hepatocellular carcinoma (HCC) cells by activating Akt/Foxo signaling pathway and increasing intracellular ROS levels. PMID- 26682008 TI - Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer. AB - Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO(*)). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO(*) production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO(*) acts as an antioxidant protecting against Fenton's reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual's risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis. PMID- 26682009 TI - Reviews on Mechanisms of In Vitro Antioxidant Activity of Polysaccharides. AB - It is widely acknowledged that the excessive reactive oxygen species (ROS) or reactive nitrogen species (RNS) induced oxidative stress will cause significant damage to cell structure and biomolecular function, directly or indirectly leading to a number of diseases. The overproduction of ROS/RNS will be balanced by nonenzymatic antioxidants and antioxidant enzymes. Polysaccharide or glycoconjugates derived from natural products are of considerable interest from the viewpoint of potent in vivo and in vitro antioxidant activities recently. Particularly, with regard to the in vitro antioxidant systems, polysaccharides are considered as effective free radical scavenger, reducing agent, and ferrous chelator in most of the reports. However, the underlying mechanisms of these antioxidant actions have not been illustrated systematically and sometimes controversial results appeared among various literatures. To address this issue, we summarized the latest discoveries and advancements in the study of antioxidative polysaccharides and gave a detailed description of the possible mechanisms. PMID- 26682010 TI - Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart. AB - We hypothesized that fibroblast growth factor-9 (FGF-9) would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p < 0.05). Additionally, the number of c-kit(+ve)/SM alpha-actin(+ve) cells and c-kit(+ve)/CD31(+ve) cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p < 0.05). Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p < 0.05). Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p < 0.05). Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function. PMID- 26682012 TI - Protective Effect of D-Limonene against Oxidative Stress-Induced Cell Damage in Human Lens Epithelial Cells via the p38 Pathway. AB - Oxidative stress, as mediated by ROS, is a significant factor in initiating the development of age-associated cataracts; D-limonene is a common natural terpene with powerful antioxidative properties which occurs naturally in a wide variety of living organisms. It has been shown to have antioxidant effect; we found that D-limonene can effectively prevent the oxidative damage caused by H2O2 and propose that the main mechanism underlying the inhibitory effects of D-limonene is the inhibition of HLECs apoptosis. In the present study, we used confocal fluorescence microscopy, flow cytometry analysis, Hoechst staining, H2DCFDA staining, transmission electron microscopy, and immunoblot analysis; the results revealed that slightly higher concentrations of D-limonene (125-1800 MUM) reduced the H2O2-induced ROS generation and inhibited the H2O2-induced caspase-3 and caspase-9 activation and decreased the Bcl-2/Bax ratio. Furthermore, it inhibited H2O2-induced p38 MAPK phosphorylation. Thus, we conclude that D-limonene could effectively protect HLECs from H2O2-induced oxidative stress and that its antioxidative effect is significant, thereby increasing the cell survival rate. PMID- 26682011 TI - High Mobility Group B Proteins, Their Partners, and Other Redox Sensors in Ovarian and Prostate Cancer. AB - Cancer cells try to avoid the overproduction of reactive oxygen species by metabolic rearrangements. These cells also develop specific strategies to increase ROS resistance and to express the enzymatic activities necessary for ROS detoxification. Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. But if this is not possible, oxidative stress finally activates signals that will lead to cell death. High mobility group B (HMGB) proteins have been previously related to the onset and progressions of cancers of different origins. The protein HMGB1 behaves as a redox sensor and its structural changes, which are conditioned by the oxidative environment, are associated with different functions of the protein. This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. Their participation in the molecular mechanisms of resistance to cisplatin, a drug commonly used in chemotherapy, is also revised. PMID- 26682015 TI - COVARIANCE ESTIMATION USING CONJUGATE GRADIENT FOR 3D CLASSIFICATION IN CRYO-EM. AB - Classifying structural variability in noisy projections of biological macromolecules is a central problem in Cryo-EM. In this work, we build on a previous method for estimating the covariance matrix of the three-dimensional structure present in the molecules being imaged. Our proposed method allows for incorporation of contrast transfer function and non-uniform distribution of viewing angles, making it more suitable for real-world data. We evaluate its performance on a synthetic dataset and an experimental dataset obtained by imaging a 70S ribosome complex. PMID- 26682013 TI - Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results. AB - The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency. PMID- 26682016 TI - Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics. AB - Cytochrome P450 17A1 (CYP17A1) is associated in the steroid hormone biosynthesis in human. As cell proliferation of prostate cancer in response to androgen steroid, an inhibition of CYP17A1 becomes an alternative approach to inhibit biosynthesis of androgen and support treatment of prostate cancer. However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD) simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy. PMID- 26682017 TI - The legend of the KJU. PMID- 26682014 TI - The Tumorigenic Roles of the Cellular REDOX Regulatory Systems. AB - The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy. PMID- 26682018 TI - Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy. AB - PURPOSE: Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. RESULTS: The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9+/-2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). CONCLUSIONS: Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab. PMID- 26682019 TI - Multiple cores of high grade prostatic intraepithelial neoplasia and any core of atypia on first biopsy are significant predictor for cancer detection at a repeat biopsy. AB - PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients. PMID- 26682020 TI - Urodynamic assessment of bladder and urethral function among men with lower urinary tract symptoms after radical prostatectomy: A comparison between men with and without urinary incontinence. AB - PURPOSE: We compared bladder and urethral functions following radical prostatectomy (RP) between men with and without urinary incontinence (UI), using a large-scale database from SNU-experts-of-urodynamics-leading (SEOUL) Study Group. MATERIALS AND METHODS: Since July 2004, we have prospectively collected data on urodynamics from 303 patients with lower urinary tract symptoms (LUTS) following RP at three affiliated hospitals of SEOUL Study Group. After excluding 35 patients with neurogenic abnormality, pelvic irradiation after surgery, or a history of surgery on the lower urinary tract, 268 men were evaluated. We compared the urodynamic findings between men who had LUTS with UI (postprostatectomy incontinence [PPI] group) and those who had LUTS without UI (non-PPI group). RESULTS: The mean age at an urodynamic study was 68.2 years. Overall, a reduced bladder compliance (<=20 mL/cmH2O) was shown in 27.2% of patients; and 31.3% patients had idiopathic detrusor overactivity. The patients in the PPI group were older (p=0.001) at an urodynamic study and had a lower maximum urethral closure pressure (MUCP) (p<0.001), as compared with those in the non-PPI group. Bladder capacity and detrusor pressure during voiding were also significantly lower in the PPI group. In the logistic regression, only MUCP and maximum cystometric capacity were identified as the related factor with the presence of PPI. CONCLUSIONS: In our study, significant number of patients with LUTS following RP showed a reduced bladder compliance and detrusor overactivity. PPI is associated with both impairment of the urethral closuring mechanism and bladder storage dysfunction. PMID- 26682021 TI - Simultaneous treatment of anterior vaginal wall prolapse and stress urinary incontinence by using transobturator four arms polypropylene mesh. AB - PURPOSE: To evaluate the medium-term efficacy and safety of transobturator four arm polypropylene mesh in the treatment of high-stage anterior vaginal wall prolapse and concomitant stress urinary incontinence (SUI). MATERIALS AND METHODS: Between September 2010 and August 2013, a prospective single-center trial was performed to evaluate women with stage>=3 anterior vaginal wall prolapse with or without SUI who presented to Labbafinejad Hospital, Teheran, Iran, and underwent anterior vaginal wall repair with polypropylene mesh. Pre- and postoperative evaluation included history; physical examination using the Pelvic Organ Prolapse Quantification system and cough stress test, both before and after reduction of prolapsed structures; Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ); urinalysis and culture; and a postvoid residual assessment. Complications were reported at a mean of 2 years of follow-up. RESULTS: A total of 71 patients underwent cystocele repair with the transobturator four-arm polypropylene mesh. Seven of the patients were lost to follow-up. There were no perioperative complications. The anatomical success rate was 87.5%. The subjective success rate was 92.1%. The PFDI and PFIQ were significantly improved after surgery (p<0.001). Among those with the simultaneous complaint of SUI, 82% were cured without any additional procedure. Three patients (4.6%) experienced vaginal mesh extrusion. Two patients (3.1%) reported worsening of dyspareunia after surgery. CONCLUSIONS: The four arms polypropylene mesh is an effective device for simultaneous correction of anterior vaginal wall prolapse and SUI with a low complication rate at a medium-term follow-up. The majority of the subgroup with concomitant SUI were cured without a second simultaneous procedure. PMID- 26682022 TI - Characteristics of urinary retention in female inpatients managed with medical treatments. AB - PURPOSE: We aimed to analyze the characteristics of urinary retention (UR) in female inpatients managed with medical treatments. MATERIALS AND METHODS: We retrospectively analyzed the medical records of female inpatients referred to the department of urology for UR at our institution from January 2009, to December 2014. UR was defined as a difficulty in self-voiding despite a sufficient urine volume or >300-mL postvoid residual. The data included patients' age, body mass index (BMI), ambulatory status, medical and surgical history, classes of taking drugs, and urinary tract infection. RESULTS: A total of 182 women were included as retention group, mean age of 72.64+/-12.94 years and BMI of 22.94+/-3.10 kg/m(2). In the chi-square analysis, cardiovascular disorders (p=0.000), diabetes mellitus (p=0.008), metastatic malignancy (p=0.008), chronic renal disorders (p=0.028) were found significantly. In the multiple logistic regression analysis, cardiovascular disorders (p=0.002; odds ratio [OR], 0.491), metastatic malignancy (p=0.013; OR, 2.616) were found to increase the risk of UR. The most common surgical history was anti-incontinence surgery (7.2%). In term of medication use, the most prescribed agents were nonsteroidal anti-inflammatory drugs (NSAIDs) (53.8%). The patients taking multiple drugs with antimuscarinic effects except of NSAIDs, narcotics and diuretics were 48 (26.4%). Urinary tract infection was identified in 43 patients (23.6%). CONCLUSIONS: UR in females managed with medical treatments could be occurred occasionally. We think that thorough attentions are needed for UR to patients with cardiovascular disorders including diabetes mellitus, metastatic malignancy, chronic renal disorders urinary tract infection, and more careful interests when managing with drugs with antimuscarinic effects. PMID- 26682023 TI - Analysis of voiding dysfunction after transobturator tape procedure for stress urinary incontinence. AB - PURPOSE: The definition of posttransobturator tape procedure (post-TOT) voiding dysfunction (VD) is inconsistent in the literature. In this study, we retrospectively investigated the risk factors for post-TOT VD by applying various definitions in one cohort. MATERIALS AND METHODS: The medical records of 449 patients were evaluated postoperatively. Acute urinary retention requiring catheterization, subjective feeling of voiding difficulty during follow-up, and postoperative postvoid residual (PVR) greater than 100 mL or PVR greater than 50% of voided volume (significant PVR) were adopted for the definition of VD. With these categories, multivariate analysis was performed for risk factors of postoperative VD. RESULTS: Ten patients (2.2%) required catheterization, 47 (10.5%) experienced postoperative voiding difficulty, and 63 (14.7%) showed significant PVR. In the multivariate logistic analysis, independent risk factors for postoperative retention requiring catheterization were previous retention history (p=0.06) and preoperative history of hysterectomy. Risk factors for subjective postoperative voiding difficulty were underactive detrusor (p=0.04) and preoperative obstructive voiding symptoms (p<0.01). Previous urinary retention history (p<0.01)) was an independent risk factor for concomitant postoperative voiding difficulty and significant PVR. Spinal anesthesia (p=0.02) and previous urinary retention history (p=0.02) were independent risk factors for significant postoperative PVR. CONCLUSIONS: With the use of several definitions of VD after the midurethral sling procedure, postoperative peak flow rate and PVR were significantly different between groups. Although there were no independent risk factors consistent with various definitions of VD, preoperative obstructive voiding symptoms and objective parameters suggesting impaired detrusor tend to have predictive power for post-TOT VD. PMID- 26682024 TI - Semen parameters from 2002 to 2013 in Korea young population: A preliminary report. AB - PURPOSE: To analyze the differences of semen parameters in Korean young population for three periods from 2002 to 2013. MATERIALS AND METHODS: A total of 516 semen samples were collected from Korean men presenting for infertility, varicoceles or other infectious problems for three periods from 2002 to 2012: January 2002-December 2003, January 2007-December 2008, and January 2012-December 2013. A standard World Health Organization procedure for semen analysis was performed for assessment of semen concentration, volume, motility, morphology, and pH. RESULTS: A total of 160, 162, 194 men constituted the study populations in 2002 to 2003, in 2007 to 2008, and in 2012 to 2013, respectively. The overall sperm parameter results suggested a statistically significant difference between 2002 to 2003 and 2012 to 2013 except pH. However, considering the data from 2007 to 2008, there were no trends in changes in overall semen parameters. Negative correlations were observed in all semen parameters with increasing age in all patients, except for pH. In addition, semen volume, motility, and morphology had higher negative correlation coefficients with age, from 2002 to 2013, serially. CONCLUSIONS: There were no significant changes in the semen parameters of Korean men from 2002 to 2013. In addition, semen volume, motility, and morphology showed higher negative correlation coefficients with age from 2002 to 2013, serially. PMID- 26682026 TI - Letter to the editor: Impact of metabolic syndrome on response to medical treatment of benign prostatic hyperplasia. PMID- 26682027 TI - The authors reply: Impact of metabolic syndrome on response to medical treatment of benign prostatic hyperplasia. PMID- 26682025 TI - Noxious electrical stimulation of the pelvic floor and vagina induces transient voiding dysfunction in a rabbit survival model of pelvic floor dystonia. AB - PURPOSE: Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior. MATERIALS AND METHODS: Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetanizing needle stimulation to the pubococcygeous (PC) muscle and controls (n=3) sham needle placement. After 7 days all animals were subjected to tetanizing transvaginal stimulation and CMG/EMG. After 5 days a final CMG/EMG was performed. RESULTS: Of rabbits that underwent needle stimulation 7 of 9 (78%) demonstrated dysfunctional CMG micturition contractions versus 6 of 12 (50%) after transvaginal stimulation. Needle stimulation of the PC musculature resulted in significant changes in: basal CMG pressure, precontraction pressure change, contraction pressure, interval between contractions and postvoid residual; with time to 3rd contraction increased from 38 to 53 minutes (p=0.008 vs. prestimulation). Vaginal noxious stimulation resulted in significant changes in: basal CMG pressure and interval between contractions; with time to 3rd contraction increased from 37 to 46 minutes (p=0.008 vs. prestimulation). Changes in cage parameters were primarily seen after direct needle stimulation. CONCLUSIONS: In a majority of animals, tetanizing electrical stimulation of the rabbit pelvic floor resulted in voiding changes suggestive of pelvic floor dysfunction as characterized by a larger bladder capacity, longer interval between contractions and prolonged contraction duration. PMID- 26682028 TI - Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial. AB - BACKGROUND: Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. METHODS: This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. RESULTS: Thirty two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after - before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after - before] of Vitamin E group = 6.37 +/- 2.85, control group = 6.57 +/- 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). CONCLUSIONS: The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy. PMID- 26682029 TI - Exploring the Role of the Public and Private Funded Primary Health Care Facilities for Children in a Pluralistic Health Care Setting of Barbados: One of the English Caribbean Countries. AB - BACKGROUND: The major objectives of this study were to evaluate the existing primary health care service provisions in the public and private sector and utilization of the services, and to assess the existing manpower and material resources. METHODS: Data were collected through interviews with the primary health care providers. Data were also collected from the records maintained at the polyclinics and the Ministry of Health Statistics. An analysis and discussion of all the available data was conducted to develop a comprehensive primary health care service utilization and resources inventory at the polyclinics. Similar data were collected from the primary care providers in the private sector. RESULTS: In the public sector, there are 8 polyclinics that provide primary health care to the children. All the polyclinics have immunization services and curative acute care. Some of the polyclinics have a range of services, including dental care, eye care, and rehabilitative care services that common to both adults and children. In the private sector, primary health care is delivered through the 76 private office and of the individual physicians and 11 grouped private practices. All of the private offices and group practices have curative acute care for children and some of the offices have immunization services. Over all 87.5% of all the immunizations were done at the polyclinics. Over all 60.1% of acute care visits were to the private sector and 39.9% to the public sector. In the public sector, 59.5% were under 5 years children while 40.5% were 5 years or older. The corresponding figures in the private care settings were 80.9% and 11.9%. CONCLUSIONS: The findings demonstrate the complimentary role of the public and the private sector in the primary health care of children in this country. While the private sector has a major role in the curative acute care of children, the public sector plays a pivotal role in the immunization services. PMID- 26682030 TI - Randomized Trial of Psychological Interventions to Preventing Postpartum Depression among Iranian First-time Mothers. AB - BACKGROUND: The current study was conducted to examine the effect of cognitive behavior therapy on the reduction postpartum mood disorder and increasing the self-esteem of at-risk Iranian mothers. METHODS: In this quasi-experimental study, 135 at-risk mothers were selected from the population by means of cluster sampling and randomly assigned into one of two groups: Intervention (n = 64), or control (n = 71). The control group received usual medical care, and the intervention group received an eight sessions' cognitive behavior program during pregnancy. Assessments were administered at two time points (pretest at the beginning of the third trimester and posttest at 2 weeks postpartum). Beck anxiety, beck depression, Edinburgh postpartum depression, (PPD) Coopersmith self esteem, and religious attitude questionnaire were used to collect data. RESULTS: The mean age of participants was 25.8 +/- 3.7 years. One-third of them had either bachelor or higher degrees in education (33%). About two-third of participants were unemployment with similar distribution in both the groups (intervention = 80%, control = 83%). The majority (70%) of the participants had cesarean section deliveries. There were no statistically significant differences respects to sociodemographic characteristics between the control and intervention groups (P > 0.05). The multivariate analysis of covariance results showed that the average scores of PPD were reduced significantly in the intervention group (P < 0.001). Also while the mean score of anxiety in the intervention group decreased from 23.31 (standard error [SE] =12.11) to 16.64 (SE = 8.33) and self-esteem increased from 29.09 (SE = 3.51) to 31.81 (SE = 2.76), no change was statistically significant in comparison to the control group. CONCLUSIONS: According to the findings of the present study, cognitive behavior intervention is effective in reducing PPD in at-risk mothers. PMID- 26682031 TI - Cell- and Gene- Based Therapeutics for Periodontal Regeneration. AB - Periodontitis is a disease of the periodontium, characterized by loss of connective tissue attachment and supporting the alveolar bone. Therefore, to regenerate these lost tissues of the periodontium researchers have included a variety of surgical procedures including grafting materials growth factors and the use of barrier membranes, ultimately resulting into regeneration that is biologically possible but clinically unpredictable. Recently a newer approach of delivering DNA plasmids as therapeutic agents is gaining special attention and is called gene delivery method. Gene therapy being considered a novel approach have a potential to channel their signals in a very systematic and controlled manner thereby providing encoded proteins at all stages of tissue regeneration. The aim of this review was to enlighten a view on the application involving gene delivery and tissue engineering in periodontal regeneration. PMID- 26682032 TI - Association between Aluminum and Silicon Concentrations in Isfahan Drinking Water and Their Health Risk Assessments. AB - BACKGROUND: High concentrations of elements such as aluminum (Al) and silicon (Si) in drinking water can affect human health. It is suggested that high daily intake of Al is associated with increased risk of neurodegenerative disorders. Si, as an antidote of Al, may decrease Al bioavailability. The study was conducted to estimate Al and Si concentration and correlation in water and evaluate their health risk. METHODS: In this cross-sectional study, water samples were collected from 20 points of water distribution system and the water treatment plant of Isfahan in spring and summer. Samples were analyzed using DR 5000. The health risk was evaluated via calculating chronic daily intake (CDI) and hazard index (HI). RESULTS: Significant negative correlation was documented between Al and Si (R = -0.482, P = 0.037 in spring, and R = -0.452, P = 0.049 in summer). These values were approximately similar in all types of Al and Si. The amounts of CDI for Al in spring and summer were 6.67E-04 and 0.002 mg/kg/day, respectively. The Al HI values were below 1 in both seasons. CONCLUSIONS: The significant correlation between Al and Si concentrations suggests that Si can eliminate Al in water, and probably it might do the same in the body. The health risk of Al intake from tap water was negligible, it was assessed in an acceptable range with an HI value of less than the standard levels. The health risk of Si remained unknown due to lack of information regarding its toxicity and adverse health effects. PMID- 26682033 TI - The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains. AB - Simple 1-substituted 5- and 6-isoxazolyl-benzimidazoles have been shown to be potent inhibitors of the BET bromodomains with selectivity over the related bromodomain of CBP. The reported inhibitors were prepared from simple starting materials in two steps followed by separation of the regioisomers or regioselectively in three steps. PMID- 26682034 TI - Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor. AB - A potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound 35, pIC50 7.2) with excellent selectivity over representatives from other KDM subfamilies has been developed; the discovery that a triazolopyridine compound binds to the active site of JmjC KDMs was followed by optimisation of the triazole substituent for KDM2A inhibition and selectivity. PMID- 26682035 TI - Special issue on bio-ontologies and phenotypes. AB - The bio-ontologies and phenotypes special issue includes eight papers selected from the 11 papers presented at the Bio-Ontologies SIG (Special Interest Group) and the Phenotype Day at ISMB (Intelligent Systems for Molecular Biology) conference in Boston in 2014. The selected papers span a wide range of topics including the automated re-use and update of ontologies, quality assessment of ontological resources, and the systematic description of phenotype variation, driven by manual, semi- and fully automatic means. PMID- 26682036 TI - 5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation. AB - 2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) and 4-carboxy-8 hydroxyquinoline (4C8HQ) with that of two other commonly used 2OG oxygenase inhibitors, N-oxalylglycine (NOG) and 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal that IOX1 has a broad spectrum of activity, as demonstrated by the inhibition of transcription factor hydroxylases, representatives of all 2OG dependent histone demethylase subfamilies, nucleic acid demethylases and gamma butyrobetaine hydroxylase. Cellular assays show that, unlike NOG and 2,4-PDCA, IOX1 is active against both cytosolic and nuclear 2OG oxygenases without ester derivatisation. Unexpectedly, crystallographic studies on these oxygenases demonstrate that IOX1, but not 4C8HQ, can cause translocation of the active site metal, revealing a rare example of protein ligand-induced metal movement. PMID- 26682037 TI - Modulating carnitine levels by targeting its biosynthesis pathway - selective inhibition of gamma-butyrobetaine hydroxylase. AB - Carnitine is essential for fatty acid metabolism, but is associated with both health benefits and risks, especially heart diseases. We report the identification of potent, selective and cell active inhibitors of gamma butyrobetaine hydroxylase (BBOX), which catalyses the final step of carnitine biosynthesis in animals. A crystal structure of BBOX in complex with a lead inhibitor reveals that it binds in two modes, one of which adopts an unusual 'U shape' conformation stabilised by inter- and intra-molecular pi-stacking interactions. Conformational changes observed on binding of the inhibitor to BBOX likely reflect those occurring in catalysis; they also rationalise the inhibition of BBOX by high levels of its substrate gamma-butyrobetaine (GBB), as observed both with isolated BBOX protein and in cellular studies. PMID- 26682038 TI - Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes. AB - BACKGROUND: Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined. METHODS/DESIGN: This is a randomized, double blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX((r)), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non-atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants. DISCUSSION: The trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627. TRIAL REGISTRATION: Primary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013-003732-72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014. PMID- 26682039 TI - Profiling oral and digital lesions in sheep in Ireland. AB - BACKGROUND: During the FMD outbreak in Ireland and the UK in 2001, there was significant uncertainty amongstveterinary practitioners and government veterinary inspectors surrounding the clinical diagnosis of FMD insheep. This situation was complicated by reports of idiopathic oral ulcers that closely resembled FMD ongross appearance which at that time were referred to as ovine mouth and gum obscure disease. METHODS: A field and abattoir study was carried out to determine the frequency, appearance and significance of oraland digital lesions in sheep in Ireland. A total of 3, 263 sheep were examined in 22 flocks, including 1, 969lambs and 1, 294 adults. A further 2,403 animals were examined by abattoir inspections. Animals bearing lesions of interest were identified, samples of the lesions were taken and subsequently examined by bacteriology, electron microscopy, serology, immunohistochemistry and histopathology. RESULTS: Forty four oral and 20 digital lesions were identified and characterised. Oral lesions were recorded mostfrequently in lambs, where the most common cause was orf virus infection. The majority of the oral lesions recorded in the adults was idiopathic and consistent with a diagnosis of idiopathic oral ulceration. A variety of digital lesions was observed, consistent with scald, foot-rot and contagious ovine digital dermatitis (CODD). All of the animals with lesions were seronegative to FMD virus (FMDV). CONCLUSIONS: There was no difficulty in differentiating these lesions from those caused by FMDV on the basis of flockhistory and careful clinical examination. PMID- 26664698 TI - Audit of antenatal screening for syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study. AB - OBJECTIVE: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in the same population and reassess the trends in HIV rates. METHODS: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border. RESULTS: Seroprevalence for HIV 0.47% (95% CI 0.30 0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL>=1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors. CONCLUSION: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies. PMID- 26682045 TI - An external evaluation of the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program in Gujarat and Uttar Pradesh, India. AB - BACKGROUND: To address inadequate coverage of oral rehydration salts (ORS) and zinc supplements for the treatment of diarrhea among children under-five, the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program was carried out from 2011-2013 in Gujarat and from 2011-2014 in Uttar Pradesh (UP), India. The program focused on improving the diarrhea treatment practices of public and private sector providers. METHODS: We conducted cross-sectional household surveys in program districts at baseline and endline and constructed state-specific logistic regression models with generalized estimating equations to assess changes in ORS and zinc treatment during the program period. RESULTS: Between baseline and endline, zinc coverage increased from 2.5% to 22.4% in Gujarat and from 3.1% to 7.0% in UP; ORS coverage increased from 15.3% to 39.6% in Gujarat but did not change in UP. In comparison to baseline, children with diarrhea in the two-weeks preceding the endline survey had higher odds of receiving zinc treatment in both Gujarat (odds ratio, OR = 11.2; 95% confidence interval (CI) 6.4-19.3) and UP (OR = 2.4; 95% CI 1.4-3.9), but the odds of receiving ORS only increased in Gujarat (OR = 3.6; 95% CI 2.7-4.8; UP OR = 0.9; 95% CI 0.7-1.2). Seeking care outside the home, especially from a public sector source, was associated with higher odds of receiving ORS and zinc. CONCLUSIONS: During the duration of the DAZT program, there were modest improvements in the treatment of diarrhea among young children. Future programs should build upon and accelerate this trend with continued investment in public and private sector provider training and supply chain sustainability, in addition to targeted caregiver demand generation activities. PMID- 26682046 TI - Global analysis of overweight prevalence by level of human development. AB - BACKGROUND: Less developed countries are increasingly afflicted with over nutrition, and the escalating overweight prevalence has become a global problem. However, a problem as global as this may not be amenable to a general set of remedial interventions applicable to all countries. METHODS: I use data from various sources, including the World Health Organization and the World Bank, to test the association of overweight prevalence with economic, social, and demographic indicators. I then split the countries up by human development index to investigate to what extent these associations vary between development levels. FINDINGS: On a global scale, overweight prevalence is most associated with gross domestic product (GDP) per capita, the proportion of a country that is rural, the proportion of elderly in a country's population, and the average years of schooling. At what magnitude, and even in which direction, these relationships go vary with a country's level of development. Generally, GDP per capita has a positive association with overweight prevalence, with the magnitude of such association for countries of very high human development more than twice of that for countries of low human development. However, proportion rural has a negative association with overweight prevalence, with the magnitude of such association for countries of low human development nearly twice of that for countries of very high human development. All four of these variables have statistically significant association with overweight prevalence in countries with low human development. CONCLUSIONS: I make policy suggestions to combat increasing overweight prevalence, based on the models that are developed, paying special attention to the differences in magnitude and direction of the regressors between human development levels. PMID- 26682047 TI - Scaling-up public sector childhood diarrhea management program: Lessons from Indian states of Gujarat, Uttar Pradesh and Bihar. AB - BACKGROUND: Diarrhea remains a leading cause of death among children under five in India. Public health sector is an important source for diarrhea treatment with oral rehydration salts (ORS) and zinc. In 2010, Micronutrient Initiative started a project to improve service delivery for childhood diarrhea management through public health sector in Gujarat, Uttar Pradesh (UP) and Bihar. This paper aims to highlight feasible strategies, experiences and lessons learned from scaling-up zinc and ORS for childhood diarrhea management in the public sector in three Indian states. METHODS: The project was implemented in six districts of Gujarat, 12 districts of UP and 15 districts of Bihar, which includes 10.5 million children. Program strategies included capacity building of health care providers, expanding service delivery through community health workers (CHWs), providing supportive supervision to CHWs, ensuring supplies and conducting monitoring and evaluation. The lessons described in this paper are based on program data, government documents and studies that were used to generate evidence and inform program scale-up. RESULTS: 140 000 health personnel, including CHWs, were trained in childhood diarrhea management. During three years, CHWs had sustained knowledge and have treated and reported more than three million children aged 2 59 months having diarrhea, of which 84% were treated with both zinc and ORS. The successful strategies were scaled-up. CONCLUSION: It is feasible and viable to introduce and scale-up zinc and ORS for childhood diarrhea treatment through public sector. Community-based service delivery, timely and adequate supplies, trained staff and pro-active engagement with government were essential for program success. PMID- 26682048 TI - Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta analysis. AB - BACKGROUND: Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children. METHODS: We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors. RESULTS: We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI. CONCLUSIONS: This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates. PMID- 26682049 TI - Burden of respiratory syncytial virus infections in China: Systematic review and meta-analysis. AB - BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. METHOD: A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. RESULTS: A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1-20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7-29.5%) and lowest in those aged >=16 years (2.8%, 95% CI 1.3-6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9-24.2%) than in outpatients (14%, 95% CI 9.6-19.9%). RSV type A accounted for 63.1% (95% CI 52.3 72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. CONCLUSION: RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority. PMID- 26682050 TI - Immunological evidence and regulatory potential for cell-penetrating antibodies in intravenous immunoglobulin. AB - Anti-DNA cell-penetrating autoantibodies have been extensively studied in autoimmune but not in normal sera. We investigated herein the presence and properties of cell-penetrating antibodies (CPAbs) in intravenous immunoglobulin (IVIg), a blood product of pooled normal human IgG. IVIg cell penetration was observed into various cell lines, as well as cells from several organs of mice injected intravenously with IVIg therapeutic dose. In all cell types examined in vitro and in vivo, intracellular IgG localized in the cytoplasm, in contrast to the nuclear accumulation of disease-related CPAbs. IVIg was found to rapidly enter cells via an energy-independent mode. The CPAb-fraction was isolated and found to be polyreactive to nuclear and cytoplasmic components; although it corresponded to ~2% of IVIg, it accounted for its inhibitory effect on splenocyte activation. Investigation of IVIg cell penetration capacity provides insight into its mechanisms of action and may account for some of its beneficial effects in numerous diseases. PMID- 26682052 TI - Lymphocyte phosphatase-associated phosphoprotein proteoforms analyzed using monoclonal antibodies. AB - Phosphatase CD45 regulates the activation of lymphocytes by controlling the level of receptor and signal molecule phosphorylation. However, it remains unknown which molecules mediate the phosphatase activity of CD45. A candidate for such a molecule is a small transmembrane adapter protein called lymphocyte phosphatase associated phosphoprotein (LPAP). LPAP forms a supramolecular complex that consists of not only CD45 molecule but also CD4 and Lck kinase. The function of LPAP has not been defined clearly. In our study, we determined the pattern of LPAP expression in various cell types and characterized its proteoforms using new monoclonal antibodies generated against the intracellular portion of the protein. We show that LPAP is a pan-lymphocyte marker, and its expression in cells correlates with the expression of CD45. The majority of T, B and NK cells express high levels of LPAP, whereas monocytes, granulocytes, monocyte-derived dendritic cells, platelets and red blood cells are negative for LPAP. Using one- and two dimensional protein gel electrophoresis, we demonstrate that LPAP has at least four sites of phosphorylation. The resting cells express at least six different LPAP phosphoforms representing mono-, di- and tri-phosphorylated LPAP. T and B cells differ in the distribution of the protein between phosphoforms. The activation of lymphocytes with PMA reduces the diversity of phosphorylated forms. Our experiments on Lck-deficient Jurkat cells show that Lck kinase is not involved in LPAP phosphorylation. Thus, LPAP is a dynamically phosphorylated protein, the function of which can be understood, when all phosphosites and kinases involved in its phosphorylation will be identified. PMID- 26682051 TI - Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses. AB - The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV 1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract. PMID- 26682053 TI - Medical case reports in the age of genomic medicine. AB - The case report has been a pillar of medical literature but has been displaced recently because of inherent risks of bias. As we move towards precision medicine, however, the case report format could provide an important method for describing disease mechanisms based on rare genetic variants. Empirical evidence reveals that many previously unexplained Mendelian diseases are accounted for by rare heterozygous alleles, de novo mutations or compound heterozygous mutations, and that disease-associated variants are often confined to the kindred of the affected individual. Elucidation of the phenotypes of these rare genetic variants will necessarily offer unique insights into disease mechanisms. Even when the association between variants in a specific gene and a disease has already been identified, individual cases are valuable. Allelic series extend both the clinical and laboratory phenotypes. Finally, the prevalence of a disease is not a reliable indicator of the therapeutic importance of the underlying mechanism, so resolving extreme phenotypes even in single cases has the potential to identify new treatment strategies relevant to more common disease. PMID- 26682055 TI - Expression analysis of surface molecules on human thymic dendritic cells with the 10th HLDA Workshop antibody panel. AB - Dendritic cells (DC) in the thymus have an important role in the establishment of central tolerance by promoting negative selection of autoreactive T cells and regulatory T-cell differentiation. Whereas human DC have recently been studied in various tissues in more detail, thymic DC subsets are still ill-defined. In the present work, we studied the binding of 71 monoclonal antibodies (mAb) submitted to the HLDA10 workshop to human CD123(+) plasmacytoid DC and the two subsets of conventional DC (cDC, CD141(+) and CD11b(+)) isolated from thymus tissue of infants undergoing corrective heart surgery. Within the panel, we found mAb binding to thymic pDC and both cDC subsets (for example, anti-Clec12A, TIM-3, Clec4A, CCR5, Axl, FLT3), but most of them additionally reacted with other thymic cell types. MAb directed to CD85h (ILT1) and the C-type lectin Clec7A (now CD369) reacted selectively with both cDC subsets, but not with other cells. Only one mAb directed to CD85g (ILT7) stained thymic pDC in a highly specific manner. Clec9A (DNGR1, now CD370) was the only tested HLDA10 antigen exclusively expressed on thymic CD141(+) cDC. The present report summarizes all data obtained. PMID- 26682056 TI - Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria. AB - Interleukin (IL)-10, a non-redundant anti-inflammatory cytokine is produced by different cells and its production involves activation of cell-specific transcriptional regulatory machinery in response to specific pathogen. We have previously demonstrated downregulated levels of IL-10 in severe falciparum malaria. The present study investigated transcriptional regulation of IL-10 in severe malaria. Comparative expression analysis of cell-specific signalling proteins and transcription factors for IL-10 production during the stage of active infection and with resolution of parasitaemia was performed. Interestingly, T-bet and GATA3, the Th1 and Th2 transcription factors, respectively, were downregulated in severe malaria with fold change values of 0.59 and 0.86. Increase in the levels of both the factors with resolution of parasitaemia implicated a role for parasite in depressed levels of these factors. Further support for probable parasite manipulation of GATA3 was obtained from negative correlation of GATA3 with parasitaemia. In addition, a role for interferon-alpha in suppressing IL-10 transcription was evident from its negative correlation with GATA3 and IL-10 levels. In summary, IL-10 transcription in Th1 and Th2 is defective and appears to have major contribution to low levels in severe malaria. PMID- 26682054 TI - Rhinovirus stimulated IFN-alpha production: how important are plasmacytoid DCs, monocytes and endosomal pH? AB - Human rhinovirus (HRV) infection is a major cause of asthma exacerbations, which appears to be linked to a defective innate immune response to infection. Although the type I interferons (IFN-alpha and IFN-beta) have a critical role in protecting against most viral infections, the cells responsible for IFN production in response to HRV and the relative importance of pattern recognition receptors located in endosomes has not been fully elucidated. In the current study we demonstrate that, using intracellular flow cytometry, >90% of the IFN alpha-producing cells in human blood mononuclear cells following HRV16 exposure are plasmacytoid dendritic cells, whereas monocytes and myeloid dendritic cells contribute only 10% and <1%, respectively, of the IFN-alpha production. Bafilomycin and chloroquine, agents that inhibit the function of endosomal toll like receptors (TLRs), significantly reduced the capacity of TLR3-, TLR7- and TLR 9-stimulated cells to produce IFN-alpha and the IFN-induced chemokine CXCL10 (IP 10). In contrast, only bafilomycin (but not chloroquine) effectively suppressed HRV16-stimulated IFN-alpha and IP-10 production, whereas neither bafilomycin or chloroquine inhibited HRV16-stimulated interleukin-6 release. Attempts to block IFN-alpha production with commercially available TLR-specific oligonucleotides were unsuccessful due to major 'off-target' effects. These findings suggest that among circulating haemopoietic cells, plasmacytoid dendritic cells and TLRs located within endosomes are critical for inducing efficient IFN-I production in response to HRVs. PMID- 26682057 TI - Profiling of primary peripheral blood- and monocyte-derived dendritic cells using monoclonal antibodies from the HLDA10 Workshop in Wollongong, Australia. AB - Dendritic cells (DCs) arise from hematopoietic stem cells and develop into a discrete cellular lineage distinct from other leucocytes. Mainly three phenotypically and functionally distinct DC subsets are described in the human peripheral blood (PB): plasmacytoid DCs (pDCs), which express the key marker CD303 (BDCA-2), and two myeloid DC subsets (CD1c(+) DC (mDC1) and CD141(+) DC (mDC2)), which express the key markers CD1c (BDCA-1) and CD141 (BDCA-3), respectively. In addition to these primary cell subsets, DCs can also be generated in vitro from either CD34(+) stem/progenitor cells in the presence of Flt3 (Fms-related tyrosine kinase 3) ligand or from CD14(+) monocytes (monocyte derived DCs (mo-DCs)) in the presence of granulocyte-macrophage colony stimulating factor+interleukin-4 (GM-CSF+IL-4). Here we compare the reactivity patterns of HLDA10 antibodies (monoclonal antibody (mAb)) with pDCs, CD1c(+) DCs and CD141(+) DCs, as well as with CD14(+)-derived mo-DCs cultured for 7 days in the presence of 100 ng/ml GM-CSF plus 20 ng/ml IL-4. A detailed profiling of these DC subsets based on immunophenotyping and multicolour flow cytometry analysis is presented. Using the panel of HLDA10 Workshop mAb, we could verify known targets selectively expressed on discrete DC subsets including CD370 as a selective marker for CD141(+) DCs and CD366 as a marker for both myeloid subsets. In addition, vimentin and other markers are heterogeneously expressed on all three subsets, suggesting the existence of so far not identified DC subsets. PMID- 26682058 TI - Development of synthetic anti-cyclic citrullinated peptide antibody and its arthritogenic role. AB - This study was undertaken to develop a novel anti-citrullinated peptide antibody (ACPA) and to investigate its arthritogenicity in a collagen-induced arthritis (CIA) model. The novel ACPA, 12G1, was developed by injecting cyclic citrullinated antigen in mice and subsequently hybridizing the B cells producing citrullinated peptide-specific antibodies with a myeloma cell line. The arthritic joints of mice with CIA and collagen antibody-induced arthritis (CAIA) as well as interleukin-1 receptor antagonist (IL-1Ra) knockout (KO) mice were stained immunohistochemically using the 12G1 antibody. Confocal immunostaining was used to identify colocalization of 12G1 with various citrullinated proteins. 12G1 in the presence or absence of chelating beads was administered to CIA mice on days 21 and 28 after type II collagen (CII) immunization to investigate 12G1 arthritogenecity. 12G1 detected citrullinated proteins in the arthritic joints of all the experimental arthritis models used. Confocal immunostaining showed that 12G1 was colocalized with well-known citrullinated proteins, including vimentin, collagen, anti-immunoglobulin binding protein and fibronectin. Staining of citrullinated proteins using 12G1 was more diffuse in CIA mice compared with CAIA and IL-1Ra KO mice. 12G1 injection apparently acted as a booster of immunization in CIA mice in combination with a single CII immunization, with this effect being abolished when 12G1 was injected with chelating beads. The novel ACPA, 12G1, identified various citrullinated proteins in the arthritic joints of three experimental arthritis models. 12G1-treated mice developed arthritis following a single CII immunization, suggesting an arthritogenic potential for ACPA in CIA mice. PMID- 26682059 TI - Cadmium removal from aqueous solution by green synthesis iron oxide nanoparticles with tangerine peel extract. AB - BACKGROUND: The adsorption process by metal oxide nanoparticles has been investigated an effective agent for removing organic and inorganic contaminants from water and wastewater. In this study, iron oxide nanoparticles were synthesized in the presence of tangerine peel extract as adsorbent for cadmium ions removal from contaminated solution. Iron oxide nanoparticles prepared by co precipitation method and tangerine peel extract was used to prevent accumulation and reduce the diameter of the particles. Effect of various parameters such as contact time, pH, metal concentration and adsorbent dosage was determined on the removal efficiency. RESULTS: The different concentrations of tangerine peel had an impact on the size of nanoparticles. As, increasing the concentration of tangerine peel extract from 2 to 6 % the average size of synthesized iron oxide nanoparticles decreased 200 nm to 50 nm. The maximum removal of cadmium ions (90 %) occurred at pH of 4 and adsorbent dose of 0.4 g/100 ml. Adsorption of cadmium ions by synthesized iron oxide nanoparticles followed Freundlich adsorption model and pseudo-second-order equation. CONCLUSION: The cadmium ions are usually soluble in acidic pH and the maximum removal of cadmium by green synthesis iron oxide nanoparticles was obtained in the pH of 4, so these nanoparticles can be a good adsorbent for the removal of cadmium from wastewater. PMID- 26682060 TI - On the thermal effect induced in tissue samples exposed to extremely low frequency electromagnetic field. AB - BACKGROUND: The influence of electromagnetic exposure on mammalian tissues was approached as a public health issue aiming to reveal the putative side effect of 50 Hz industrial and domestic supply source (i) during aliments storage near such sources; (ii) in people staying couple of hours in the proximity of conducting wires. MATERIALS AND METHODS: Fluorescence emission based thermal sensor was used to emphasize temperature dynamics of fresh meat samples during controlled electromagnetic exposure in Helmholtz coils adjusted to deliver 50 Hz / (4/10) mT electromagnetic field in their inner volume. Fluoroptic temperature probe with 0.1 degrees C accuracy measurement and data acquisition software allowed reading temperature every second, in the tissue volume during exposure. RESULTS: The temperature dynamics curves of ex-vivo porcine tissues like liver, kidney, brain, muscle, lung, and bone, were comparatively analyzed - the choosing of the mammalian species being justified by metabolic and physiological similarities with human body. The curve slopes appear to be the same for the range of initial temperatures chosen to perform the tests (20.0 +/- 0.1 degrees C), the temperature increase reaching around 2.0 degrees C for the magnetic flux density of 10 mT. Quantitative dependence was evidenced between the thermal effect and the magnetic flux density. CONCLUSIONS: The technical interpretation is based on heating effect, on bioimpedance increasing and on water vaporization during wet sample exposure. The biomedical aspects derive from the degrading effects of food heating as well as from possible in vivo effects of living body exposure. PMID- 26682061 TI - Current questions and possible controversies in autophagy. AB - Interest in autophagy has exploded over the last decade, with publications highlighting crosstalk with several other cellular processes including secretion, endocytosis, and cell suicide pathways including apoptosis. Autophagy proteins have also been implicated in other cellular processes independently of their roles in autophagy, creating complexities in the interpretation of autophagy (Atg) mutant gene data. Interestingly, this self-eating process is a survival mechanism that can also promote cell death, but when and how autophagy may 'switch' its function is still under debate. Indeed, there are currently many models of how autophagy actually influences cell death. In this review, we highlight some outstanding questions and possible controversies in the autophagy field. PMID- 26682062 TI - A Study of Naturally Acquired Canine Babesiosis Caused by Single and Mixed Babesia Species in Zambia: Clinicopathological Findings and Case Management. AB - A retrospective and prospective analysis of clinical records of dogs diagnosed with Babesia infections was carried out for the years 2000 to 2013 from practices in Lusaka, Zambia. Records of 363 dogs with confirmed Babesia infections were analysed using demographic factors including sex, breed, age, and clinical signs in relation to haematological findings and Babesia species. The clinical and laboratory findings observed are described as well as Babesia species identification. The study included 18 breeds and the highest proportion were mongrels (32.2%), males representing 64.5% of the population. The most common presenting problems were anorexia (65.3%) and lethargy/weakness (65.3%). The most common clinical signs were fever (87.3%), pallor (52.3%), lymphadenopathy (47.4%), and presence of ticks (44.9%). Anaemia (96.4%) and nucleated erythrocytes (42.2%) were the most common laboratory findings. A mixed infection of Babesia rossi and Babesia gibsoni was present in 59.7% of dogs, whilst 8% and 32.2% had B. rossi and B. gibsoni as a single infection, respectively. Case management mainly involved therapy with tetracyclines and imidocarb and was usually accompanied by clinical improvement. This study highlights, for the first time, the presence of B. gibsoni in natural dog populations in Zambia, where previously only B. rossi was reported. PMID- 26682063 TI - Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model. AB - Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma. PMID- 26682064 TI - Correlation of Vitreous Vascular Endothelial Growth Factor and Uric Acid Concentration Using Optical Coherence Tomography in Diabetic Macular Edema. AB - Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical coherence tomography (OCT) and visual acuity (VA). Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR) and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT), cube volume (CV), cube average thickness (CAT), and serous retinal detachment (SRD). Results. In DME group, intravitreal concentrations of VEGF (p < 0.001), UA (p = 0.038), and total protein (p < 0.001) were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (d = 0.559, p = 0.03) but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group correlated with increase in CV (d = 0.515/p = 0.041). None of the OCT parameters correlated with the VA. Conclusions. The results suggest that the CV might be assessor of anti-VEGF therapy efficacy. Second, apart from VEGF, the role of UA in the pathogenesis and progression of DR should be considered. PMID- 26682065 TI - Transcranial Magnetic Stimulation for Status Epilepticus. AB - Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted. PMID- 26682066 TI - Spousal Presence as a Nonpharmacological Pain Management during Childbirth: A Pilot Study. AB - Background. Measures of spousal effect during parturient pain should take a tripartite approach involving the parturients, spouses, and midwives. Aim. To develop and validate three questionnaires measuring spousal presence in management of parturient pain in Nigeria. Methods. There are two phases: (1) development of questionnaires, Abuja Instrument for Midwives (AIM), Abuja Instrument for Parturient Pain (AIPP), and Abuja Instrument for Parturient Spouses (AIPS), utilizing literatures, Kuopio instrument for fathers (KIF) and expertise of health professionals, and (2) pilot study to validate the questionnaires which were administered in two hospitals in Nigeria: midwives (n = 10), parturients (n = 10), and spouses (n = 10). Results. Internal consistency for the three questionnaires indicated Cronbach's alpha coefficient of 0.789 (AIM), 0.802 (AIPP), and 0.860 (AIPS), while test-retest reliability was r = 0.99 (AIM), r = 0.99 (AIPP), and r = 0.90 (AIPS). Conclusions. AIM, AIPP, and AIPS provide a means of investigating the effectiveness of spousal presence in management of parturient pain in Nigeria. However, further testing of each instrument is needed in a larger population to replicate the beneficial findings of AIMS, AIPP, and AIPS which can contribute rigor to future studies. PMID- 26682067 TI - Comparison of Chemical and Mechanical Prophylaxis of Venous Thromboembolism in Nonsurgical Mechanically Ventilated Patients. AB - Background. Thromboembolic events are major causes of morbidity, and prevention is important. We aimed to compare chemical prophylaxis (CP) and mechanical prophylaxis (MP) as methods of prevention in nonsurgical patients on mechanical ventilation. Methods. We performed a retrospective study of adult patients admitted to the Cooper University Hospital ICU between 2002 and 2010. Patients on one modality of prophylaxis throughout their stay were included. The CP group comprised 329 patients and the MP group 419 patients. The primary outcome was incidence of thromboembolic events. Results. Acuity measured by APACHE II score was comparable between the two groups (p = 0.215). Univariate analysis showed 1 DVT/no PEs in the CP group and 12 DVTs/1 PE in the MP group (p = 0.005). Overall mortality was 34.3% and 50.6%, respectively. ICU LOS was similar. Hospital LOS was shorter in the MP group. Multivariate analysis showed a significantly higher incidence of events in the MP prophylaxis group (odds ratio 9.9). After excluding patients admitted for bleeding in both groups, repeat analysis showed again increased events in the MP group (odds ratio 2.9) but this result did not reach statistical significance. Conclusion. Chemical methods for DVT/PE prophylaxis seem superior to mechanical prophylaxis in nonsurgical patients on mechanical ventilation and should be used when possible. PMID- 26682069 TI - Comparing Three Dual-Task Methods and the Relationship to Physical and Cognitive Impairment in People with Multiple Sclerosis and Controls. AB - Dual-tasking (DT) is a measure to detect impairments in people with multiple sclerosis (MS). We compared three DT methods to determine whether cognitive (Montreal Cognitive Assessment (MoCA)) or physical disability (Expanded Disease Severity Scale; EDSS) was related to DT performance. We recruited MS participants with low disability (<3 EDSS, n = 13) and high disability (>=3 EDSS, n = 9) and matched controls (n = 13). Participants walked at self-selected (SS) speed on an instrumented walkway (Protokinetics, Havertown, USA), followed by DT walks in randomized order: DT ABC (reciting every second letter of the alphabet), DT 7 (serially subtracting 7's from 100), and DT 3 (counting upwards, leaving out multiples and numbers that include 3). DT 7 resulted in the most consistent changes in performance. Both MS and control groups reduced velocity and cadence and shortened step length during DT with no significant differences between groups. Control subjects widened stride width by about 1 cm while MS subjects (collapsed as one group) did not. MS subjects with higher disability significantly increased percentage time in double support during DT compared to SS (F = 12.95, p < 0.001). The change in DS was related to cognitive and not physical disability (r = 0.54, p < 0.05). PMID- 26682068 TI - A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model. AB - An updated model of the GABA(A) benzodiazepine receptor pharmacophore of the alpha5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) alpha5 subtype selective compounds were synthesized, notably alpha5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2'F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for alpha5beta2gamma2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the alpha5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to alpha1beta2gamma2, alpha2beta2gamma2, and alpha3beta2gamma2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors. PMID- 26682070 TI - New Insights into the Role of Metformin Effects on Serum Omentin-1 Levels in Acute Myocardial Infarction: Cross-Sectional Study. AB - Background. Serum omentin-1 level was low in the most types of ischemic heart disease compared to normal subjects; it also dependently correlated with coronary heart disease; thus, omentin-1 is regarded as a novel biomarker in IHD. Objective. The aim of the present study was to establish the links between omentin-1 and acute myocardial infarction in metformin patients. Subjects and Methods. A cross-sectional study was performed on eighty-five patients with type II DM and acute MI. They are divided as follows: Group I, 62 patients with type II DM who received metformin prior to onset of acute MI; Group II, 23 patients with type II DM who did not receive metformin prior to onset of acute MI; and Group III, 30 normal healthy controls. Venous blood was drawn from each participant for determination of lipid profile, plasma omentin-1, cardiac troponin-I (cTn-I) and other routine tests. Results. Patients that presented with acute MI that received metformin show a significant difference in all biochemical parameters (p < 0.001); metformin increases serum omentin-1 level and decreases serum cardiac troponin-I level compared with control subjects and nonmetformin treated patients. Conclusion. Metformin pharmacotherapy increases omentin-1 serum levels and may be regarded as a potential agent in the prevention of the occurrences of acute MI in diabetic patients. PMID- 26682071 TI - Growing Up: Not an Easy Transition-Perspectives of Patients and Parents regarding Transfer from a Pediatric Liver Transplant Center to Adult Care. AB - The transition from pediatric to adult care is a critical time when children with chronic illness sustain high morbidity and mortality. Transition services need to be focused on the adolescents' needs, which may differ from those perceived by healthcare providers. In this study, a survey of 31 patients with chronic liver disease and/or liver transplant who were "transferred" to adult services within the last 3 years was conducted. Patients were asked about their current health status and their perceptions of the overall transfer process. The mean age at transfer was 19.81 (18-21) years. Almost half the patients (47%) were not seen at the adult facility until 2-6 months after leaving the Children's hospital and 20% were not seen until 6-12 months. About 20% had their first contact with adult services through an emergency room visit. About 19% reported being out of medication during transition. Of the transplanted patients, 19% were being evaluated for a retransplant. The majority (82%) felt that an increased emphasis on promoting independence and "letting go" both by parents and by pediatric care providers was critical in their transition to independence and adult care services. This study provides thought-provoking insights, which are critical in designing the ideal transition program for children with chronic diseases. PMID- 26682072 TI - Distinct Functions of Endophilin Isoforms in Synaptic Vesicle Endocytosis. AB - Endophilin isoforms perform distinct characteristics in their interactions with N type Ca(2+) channels and dynamin. However, precise functional differences for the endophilin isoforms on synaptic vesicle (SV) endocytosis remain unknown. By coupling RNA interference and electrophysiological recording techniques in cultured rat hippocampal neurons, we investigated the functional differences of three isoforms of endophilin in SV endocytosis. The results showed that the amplitude of normalized evoked excitatory postsynaptic currents in endophilin1 knockdown neurons decreased significantly for both single train and multiple train stimulations. Similar results were found using endophilin2 knockdown neurons, whereas endophilin3 siRNA exhibited no change compared with control neurons. Endophilin1 and endophilin2 affected SV endocytosis, but the effect of endophilin1 and endophilin2 double knockdown was not different from that of either knockdown alone. This result suggested that endophilin1 and endophilin2 functioned together but not independently during SV endocytosis. Taken together, our results indicate that SV endocytosis is sustained by endophilin1 and endophilin2 isoforms, but not by endophilin3, in primary cultured hippocampal neurons. PMID- 26682074 TI - Recurrent Postmyocardial Infarction Ventricular Tachycardia: An Unusual Culprit. AB - Although temporary transvenous pacing is life-saving in patients with myocardial infarction who develop bradyarrhythmias, the electrical complications resulting from it can be fatal and are rarely reported. We report here a patient with acute inferior wall myocardial infarction who required temporary transvenous pacing due to second-degree atrioventricular block accompanied with hypotension. Following coronary angiography and successful revascularisation, the patient developed multiple episodes of monomorphic and polymorphic ventricular tachycardia as well as ventricular fibrillation which on careful inspection were found to be initiated by fusion of the intrinsic and paced complexes. The problem of malignant ventricular tachycardia was solved by simple removal of the pacing lead. To the best of our knowledge, malignant ventricular tachycardia of both monomorphic and polymorphic types initiated by fusion complexes in a paced patient has not been reported in literature. PMID- 26682075 TI - Enterococcus faecalis Septicemia and Vertebral Osteomyelitis after Transrectal Ultrasound Guided Biopsy of the Prostate. AB - Transrectal ultrasound guided prostate biopsy (TRUS) has rarely been associated with disseminated infection, yet the occurrence appears to be increasing. Resistance to fluoroquinolones, the most commonly used prophylaxis, is one of the likely causes, with Escherichia coli being the most commonly reported cause of these infections. Herein we present what is, to our knowledge, the first case of Enterococcus faecalis septicemia and vertebral osteomyelitis after TRUS. Previously reported cases of this condition are referenced also. PMID- 26682076 TI - Severe Legionnaires' Disease Complicated by Rhabdomyolysis and Clinically Resistant to Moxifloxacin in a Splenectomised Patient: Too Much of a Coincidence? AB - We here report a case of Legionnaires' disease in a splenectomised patient, complicated by rhabdomyolysis and acute renal failure and characterized by a poor clinical response to moxifloxacin. Splenectomy is not included among the factors, typically associated with higher risk or mortality in patients with Legionellosis. However, our report is consistent with previous case reports describing severe Legionella infections in asplenic subjects. The possibility that functional or anatomic asplenia may be a factor predisposing to severe clinical course or poor response to therapy in patients with Legionella infection cannot be excluded, deserving further investigation in the future. More studies are required in order to clarify the underlying pathophysiological mechanisms that connect asplenia, immunological response to Legionella, and pathogen's resistance to antibiotics. PMID- 26682073 TI - Physical Exercise as a Diagnostic, Rehabilitation, and Preventive Tool: Influence on Neuroplasticity and Motor Recovery after Stroke. AB - Stroke remains a leading cause of adult motor disabilities in the world and accounts for the greatest number of hospitalizations for neurological disease. Stroke treatments/therapies need to promote neuroplasticity to improve motor function. Physical exercise is considered as a major candidate for ultimately promoting neural plasticity and could be used for different purposes in human and animal experiments. First, acute exercise could be used as a diagnostic tool to understand new neural mechanisms underlying stroke physiopathology. Indeed, better knowledge of stroke mechanisms that affect movements is crucial for enhancing treatment/rehabilitation effectiveness. Secondly, it is well established that physical exercise training is advised as an effective rehabilitation tool. Indeed, it reduces inflammatory processes and apoptotic marker expression, promotes brain angiogenesis and expression of some growth factors, and improves the activation of affected muscles during exercise. Nevertheless, exercise training might also aggravate sensorimotor deficits and brain injury depending on the chosen exercise parameters. For the last few years, physical training has been combined with pharmacological treatments to accentuate and/or accelerate beneficial neural and motor effects. Finally, physical exercise might also be considered as a major nonpharmacological preventive strategy that provides neuroprotective effects reducing adverse effects of brain ischemia. Therefore, prestroke regular physical activity may also decrease the motor outcome severity of stroke. PMID- 26682077 TI - Primary Endometrial Adenocarcinoma with Signet-Ring Cells: A Rarely Observed Case and Review of the Literature. AB - An extremely rare case of a "primary endometrial adenocarcinoma with signet-ring cells" is presented in this study with microscopical images of the characteristic coexistence of the tumour and intermediate precancerous areas containing signet ring cells. PMID- 26682078 TI - Vulvar Epidermoid Cyst and Type 2 Radical Genital Mutilation. AB - About 100 million women are estimated to be circumcised globally. Various rates of complications have been encountered, especially after circumcision, such as bleeding, infection, shock, menstrual irregularity, difficulty in urination or common urinary tract infections, inguinal pain, difficulty in sexual intercourse, and genital circumcision scar especially at the vulvar region, and cystic or solid character mass in short and long term. Furthermore, the maternal-fetal morbidity and mortality increase due to bleeding and fistula, which develop after prolonged labor, travail, and difficult labors. Our aim in this paper was to discuss a 42-year-old multiparous female case who had undergone type 2 radical genital mutilation (circumcision) when she was 7 years of age, along with the literature, which has been evaluated for the gradually growing mass at the left inguinal canal region in the last 10 years and diagnosed as epidermoid inclusion cyst developing secondary to postcircumcision surgical ground trauma, since there was no other case found in the literature search that had been circumcised at such an early age and developing after circumcision at such advanced age, and, therefore, this is suggested to be the first case on this subject. PMID- 26682079 TI - Poorly Differentiated Neuroendocrine Tumor of the Rectum Coexistent with Giant Rectal Villous Adenoma Presenting as McKittrick-Wheelock Syndrome. AB - McKittrick-Wheelock Syndrome is a rare disorder, noted for electrolyte and fluid depletion caused by secretory colorectal adenomas and carcinomas. We report here the first reported case of a 55-year-old man with a large rectal villous adenoma coexistent with a poorly differentiated neuroendocrine tumor of rectum presenting with McKittrick-Wheelock Syndrome. Palliative chemotherapy resulted in complete resolution of symptoms and improved quality of life. PMID- 26682080 TI - MYC Amplification in Angiosarcoma Arising from an Arteriovenous Graft Site. AB - Angiosarcoma arising in association with an arteriovenous graft (AVG) or fistula is a unique clinicopathologic scenario that appears to be gaining recognition in the literature. Among reported cases, none has described high-level MYC gene amplification, a genetic aberration that is increasingly unifying the various clinicopathologic subdivisions of angiosarcoma. We therefore report the MYC gene status in a case of angiosarcoma arising at an AVG site. PMID- 26682081 TI - A Case of Hemolytic Disease of the Newborn due to Di (a) Antibody. AB - Anti-Di(a) is a clinically significant red cell antibody known to cause hemolytic disease of the newborn. Here, we report on a case of mild hemolytic disease of the newborn caused by Di(a) antibody. The mother had three prior pregnancies with no history of blood transfusion. She delivered a preterm 35-week-old female newborn by cesarean section. The neonate developed anemia and mild icterus on postnatal day five with hemoglobin of 9500 mg/dL and total bilirubin of 10 mg/dL. The direct antiglobulin test on the neonate's red blood cells was positive. The maternal serum and an eluate from the infant RBCs were negative in routine antibody detection tests but were positive using commercially prepared Di(a+) red cells. The neonate was discharged home in stable condition following treatment with erythropoietin and phototherapy. When a newborn has a positive DAT in the absence of major blood group incompatibility or commonly detected RBC antibodies, an antibody to a low frequency antigen such as Di(a) must be considered. Further immunohematology tests are required to determine presence of the antibody and the clinician must be alerted to closely monitor the infant for signs of anemia and hemolysis. PMID- 26682082 TI - Two Patients with Fulminant Clostridium difficile Enteritis Who Had Not Undergone Total Colectomy: A Case Series and Review of the Literature. AB - Introduction. Clostridium difficile is the most common cause of healthcare associated infectious diarrhea, and its most common clinical manifestation is pseudomembranous colitis. Small bowel enteritis is reported infrequently in the literature and typically occurs only in patients who have undergone ileal pouch anastomosis due to inflammatory bowel disease or total abdominal colectomy for other reasons. Presentation of Cases. We report here two cases in which patients developed small bowel C. difficile enteritis in the absence of these underlying conditions. Discussion. Neither patient had underlying inflammatory bowel disease and both had a significant amount of colon remaining. Conclusion. These two cases demonstrate that small bowel C. difficile enteritis should be included in the differential diagnosis of patients on antibiotic therapy who demonstrate signs and symptoms of worsening abdominal disease during their postoperative course, even if they lack the major predisposing factors of inflammatory bowel disease or history of total colectomy. PMID- 26682083 TI - Pisa Syndrome in Parkinson's Disease: Electromyographic Aspects and Implications for Rehabilitation. AB - Pisa Syndrome (PS) is a real clinical enigma, and its management remains a challenge. In order to improve the knowledge about resting state and during maximal voluntary muscle contraction (MVMC) of the axial muscles, we described the electromyography results of paraspinal muscles, rectus abdominis, external oblique, and quadratus lumborum of both sides of 60 patients. Electromyography was assessed at rest, during MVMC while bending in the opposite direction of the PS and during MVMC while bending in the direction of the PS. The MVMC gave information about the interferential pattern (INT) or subinterferential pattern (sub-INT). We defined asymmetrical activation (AA) when a sub-INT was detected on the muscle on the side opposite to the PS bending and an INT of same muscle in the direction of PS bending. We observed significant AA during MVMC only in the external oblique muscles in 78% of the subjects. Our results of asymmetric ability to generate maximal voluntary force of the external oblique muscles support a central dissynchronisation of axial muscles as a significant contributor for the bending of the spine in erect position. These results could have important implication to physiotherapy and the use of botulinum toxin in the treatment of PS. PMID- 26682084 TI - A Combined Raman Spectroscopic and Thermogravimetric Analysis Study on Oxidation of Coal with Different Ranks. AB - Raman spectroscopy and nonisothermal thermogravimetric analysis (TGA) measurements have been reported for different rank coals (lignite, bituminous coal, and anthracite) and the relationship between the measurements was examined. It was found that the Raman spectra parameters can be used to characterize structure changes in the different rank coals, such as the band area ratios based on the curve-fitted results. Higher ranked coal was found to have higher values of I GR/I All and I (G + GR)/I All but lower values of I D/I (G+GR), I DL/I (G+GR), I (S + SL)/I (G+GR), and I (GL+GL')/I (G+GR). The oxidation properties of the coal samples were characterized by the reactivity indexes T ig, T 20%, and T max from TGA data which were found to correlate well with the band area ratios of I GR/I All, I (G + GR)/I All, and I (S + SL)/I (G+GR). Based on these correlations, the Raman band area ratios were found to correlate with the oxidation activity of coal providing additional structural information which can be used to understand the changes in the TGA measurements. PMID- 26682085 TI - Development of Sensitive and Specific Analysis of Vildagliptin in Pharmaceutical Formulation by Gas Chromatography-Mass Spectrometry. AB - A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for the determination of vildagliptin (VIL) in pharmaceutical formulation. Prior to GC-MS analysis, VIL was efficiently derivatized with MSTFA/NH4I/beta-mercaptoethanol at 60 degrees C for 30 min. The obtained O-TMS derivative of VIL was detected by selected ion monitoring mode using the diagnostic ions m/z 223 and 252. Nandrolone was chosen as internal standard. The GC-MS method was fully validated by the following validation parameters: limit of detection (LOD) and quantitation (LOQ), linearity, precision, accuracy, specificity, stability, robustness, and ruggedness. LOD and LOQ were found to be 1.5 and 3.5 ng mL(-1), respectively. The GC-MS method is linear in the range of 3.5-300 ng mL(-1). The intra- and interday precision values were less than <=3.62%. The intra- and interday accuracy values were found in the range of -0.26-2.06%. Finally, the GC-MS method was successfully applied to determine VIL in pharmaceutical formulation. PMID- 26682086 TI - Giant cell tumors of the clivus: Case report and literature review. AB - BACKGROUND: Clival giant cell tumors (GCTs) are extremely rare with only eight cases reported to date, and malignant transformation is quite rare. Herein, we report a case of an uncontrolled clival GCT, which was transformed malignant, and review the literature. CASE DESCRIPTION: A 25-year-old man experienced double vision for 1 month. Computed tomography and magnetic resonance imaging revealed a clival tumor. The endonasal endoscopic transsphenoidal approach (EEA) was used, and partial resection was performed because of massive bleeding. Histological examination showed a GCT. After radiation therapy, the tumor recurred; the EEA and the anterior transpetrosal approaches were used to perform second and third operations, respectively. The MIB-1 index increased from 4.2% to 26.3%. CONCLUSIONS: GCTs are difficult to treat because of their location, vascularity, and the potential for malignant transformation. PMID- 26682087 TI - Cranial and spinal leptomeningeal dissemination in esthesioneuroblastoma: Two reports of distant central nervous system metastasis and rationale for treatment. AB - BACKGROUND: Esthesioneuroblastoma is a locally aggressive cancer of the nasal cavity. While systemic metastasis can occur in 10-30% of patients, there are only six reported cases of distal metastasis from leptomeningeal dissemination. CASE DESCRIPTION: The authors report two cases of esthesioneuroblastoma treated previously with multimodal therapy in which distal metastatic recurrence was found and describe their treatment protocol, which has resulted in long-term success. CONCLUSION: Understanding the drivers of leptomeningeal dissemination in more prevalent primary neuroectodermal tumors may hold the key to developing successful treatment algorithms for this disease. PMID- 26682088 TI - Endoscopic biopsy for the diagnosis of neurosarcoidosis at the fourth ventricle outlet with hydrocephalus. AB - BACKGROUND: Fourth ventricle mass lesion in neurosarcoidosis is very rare and difficult to be diagnosed pathologically. We report a rare case of progressive hydrocephalus associated with neurosarcoidosis mass lesion located at the fourth ventricle outlet and suprasellar region. CASE DESCRIPTION: A 23-year-old man had a disturbance of consciousness and neck stiffness with fever. Magnetic resonance imaging revealed diffuse leptomeningeal enhancement, and the obstructive mass lesions at the outlet of the fourth ventricle. We performed an endoscopic biopsy of the enhanced lesion at the foramen Magendie, via foramen Monro and the aqueduct of the midbrain. Pathologically, the diagnosis of neurosarcoidosis was confirmed, and we started treatment with prednisolone. His neurological symptoms disappeared after ventriculo-peritoneal shunt and steroid therapy, and he was discharged without deficit 40 days after emergent admission. CONCLUSION: Endoscopic procedure is less invasive and more effective for biopsy of neurosarcoidosis with hydrocephalus, even if the lesion is located at the fourth ventricle outlet. PMID- 26682089 TI - A case of metastatic brain tumor in the perfusion territory of superficial temporal artery-middle cerebral artery anastomosis. AB - BACKGROUND: We report a rare case of metastatic tumor in the perfusion territory of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. CASE DESCRIPTION: A 63-year-old man, who had undergone left STA-MCA anastomosis in the treatment of occlusion of internal carotid artery 4 years ago, presented with a hyperintense lesion on T2-weighted image in the left frontal lobe, the perfusion territory of the prior bypass. Follow-up magnetic resonance imaging 1 month later showed enhanced tumor within the T2 hyperintense lesion. A total removal of the tumor through another craniotomy was performed. The pathologic diagnosis was metastatic carcinoma. CONCLUSION: This is the first report of the metastatic carcinoma by seeding of tumor cells through STA-MCA bypass flow. PMID- 26682090 TI - Surgical management of recurrent Cushing's disease in pregnancy: A case report. AB - BACKGROUND: Cushing's disease is a condition rarely encountered during pregnancy. It is known that hypercortisolism is associated with increased maternal and fetal morbidity and mortality. When hypercortisolism from Cushing's disease does occur in pregnancy, the impact of achieving biochemical remission on fetal outcomes is unknown. We sought to clarify the impact of successful surgical treatment by presenting such a case report. CASE DESCRIPTION: A 38-year-old pregnant woman with recurrent Cushing's disease after 8 years of remission. The patient had endoscopic transsphenoidal of her pituitary adenoma in her 18(th) week of pregnancy. The patient had postoperative biochemical remission and normal fetal outcome with no maternal complications. CONCLUSION: Transsphenoidal surgery for Cushing's disease can be performed safely during the second trimester of pregnancy. PMID- 26682093 TI - Scientific Pride or Prejudice. PMID- 26682091 TI - Arm Posturing in a Patient Following Stroke: Dystonia, Levitation, Synkinesis, or Spasticity? AB - BACKGROUND: Post-stroke movement disorders occur in up to 4% of stroke patients. The movements can be complex and difficult to classify, which presents challenges when attempting to understand the clinical phenomenology and provide appropriate treatment. CASE REPORT: We present a 64-year-old male with an unusual movement in the arm contralateral to his ischemic stroke. The primary feature of the movement was an involuntary elevation of the arm, occurring only when he was walking. DISCUSSION: The differential diagnosis includes dystonia, spontaneous arm levitation, synkinesis, and spasticity. We discuss each of these diagnostic possibilities in detail. PMID- 26682092 TI - Environmental and Genetic Influences on Neurocognitive Development: The Importance of Multiple Methodologies and Time-Dependent Intervention. AB - Genetic mutations and environmental factors dynamically influence gene expression and developmental trajectories at the neural, cognitive, and behavioral levels. The examples in this article cover different periods of neurocognitive development-early childhood, adolescence, and adulthood-and focus on studies in which researchers have used a variety of methodologies to illustrate the early effects of socioeconomic status and stress on brain function, as well as how allelic differences explain why some individuals respond to intervention and others do not. These studies highlight how similar behaviors can be driven by different underlying neural processes and show how a neurocomputational model of early development can account for neurodevelopmental syndromes, such as autism spectrum disorders, with novel implications for intervention. Finally, these studies illustrate the importance of the timing of environmental and genetic factors on development, consistent with our view that phenotypes are emergent, not predetermined. PMID- 26682094 TI - Success in Spine Care: The Proof Is in the Measurements, Part II. PMID- 26682095 TI - The Practical Application of Clinical Prediction Rules: A Commentary Using Case Examples in Surgical Patients with Degenerative Cervical Myelopathy. AB - Study Design Commentary. Objective This commentary aims to discuss the practical applications of a clinical prediction rule (CPR) developed to predict functional status in patients undergoing surgery for the treatment of degenerative cervical myelopathy. Methods Clinical cases from the AOSpine CSM-North America study were used to illustrate the application of a prediction rule in a surgical setting and to highlight how this CPR can be used to ultimately enhance patient care. Results A CPR combines signs and symptoms, patient characteristics, and other predictive factors to estimate disease probability, treatment prognosis, or risk of complications. These tools can influence allocation of health care resources, inform clinical decision making, and guide the design of future research studies. In a surgical setting, CPRs can be used to (1) manage patients' expectations of outcome and, in turn, improve overall satisfaction; (2) facilitate shared decision making between patient and physician; (3) identify strategies to optimize surgical results; and (4) reduce heterogeneity of care and align surgeons' perceptions of outcome with objective evidence. Conclusions Valid and clinically-relevant CPRs have tremendous value in a surgical setting. PMID- 26682096 TI - Is Hydronephrosis a Complication after Anterior Lumbar Surgery? AB - Study Design Prospective follow-up design. Objective Ureteral injury is a recognized complication following gynecologic surgery and can result in hydronephrosis. Anterior lumbar surgery includes procedures like anterior lumbar interbody fusion (ALIF) and total disk replacement (TDR). Anterior approaches to the spine require mobilization of the great vessels and visceral organs. The vascular supply to the ureter arising from the iliac arteries may be compromised during midline retraction of the ureter, which could theoretically lead to ureter ischemia and stricture with subsequent hydronephrosis formation. Methods Potential candidates with previous ALIF or TDR via anterior retroperitoneal access between January 2008 and March 2012 were chosen from those operated on by a single surgeon in a university hospital setting (n = 85). Renal ultrasound evaluation of hydronephrosis was performed on all participants. Simple descriptive and inferential statistics were used to generate results. Results A total of 37 voluntary participants were recruited (23 male, 14 female subjects; average age 51.8 years). The prevalence of hydronephrosis in our population was 0.0% (95% confidence interval 0 to 8.1%). Conclusions Retraction of the ureter across the midline in ALIF and TDR does not result in an increase in hydronephrosis and appears to be a safe surgical technique. PMID- 26682097 TI - Comparison of Silicate-Substituted Calcium Phosphate (Actifuse) with Recombinant Human Bone Morphogenetic Protein-2 (Infuse) in Posterolateral Instrumented Lumbar Fusion. AB - Study Design Randomized controlled trial. Objective The aim of this study was to assess the efficacy of the bone grafting substitute silicate-substituted calcium phosphate (SiCaP) compared with recombinant human bone morphogenetic protein 2 (rhBMP-2) and to evaluate the clinical outcomes over a period of 2 years. Methods Patients undergoing PLF surgery for DDD at a single center were recruited and randomized to one of two groups: SiCaP (n = 9) or rhBMP-2 (n = 10). One patient withdrew prior to randomization and another from the rhBMP-2 group after randomization. The radiologic and clinical outcomes were examined and compared. Fusion was assessed at 12 months with computed tomography and plain radiographs. Clinical outcomes were evaluated by recording measures of pain, quality of life, disability, and neurologic status from 6 weeks to 2 years postoperatively. Results In the SiCaP and rhBMP-2 groups, fusion was observed in 9/9 and 8/9 patients, respectively. Pain and disability scores were reduced and quality of life increased in both groups. Leg pain, disability, and satisfaction scores were similar between the groups at each postoperative point; however, back pain was less at 6 weeks and quality of life was higher at 6 months in the SiCaP group than the rhBMP-2 group. Conclusions SiCaP and rhBMP-2 were comparable in terms of achieving successful bone growth and fusion. Both groups achieved similar alleviation of pain and improved quality of life and neurologic, satisfaction, and return to work outcomes following PLF surgery. PMID- 26682098 TI - The Outcome of Using Closed Suction Wound Drains in Patients Undergoing Lumbar Spine Surgery: A Systematic Review. AB - Study Design Systematic review. Objective Determine whether closed suction wound drains decrease the incidence of postoperative complications compared with no drain use in patients undergoing spine surgery for lumbar degenerative conditions. Methods Electronic databases and reference lists of key articles were searched up through January 22, 2015, to identify studies comparing the use of closed suction wound drains with no drains in spine surgery for lumbar degenerative conditions. Outcomes assessed included the cumulative incidence of epidural hematoma, superficial and deep wound infection, and postoperative blood transfusion. The overall strength of evidence across studies was based on precepts outlined by the Grades of Recommendation Assessment, Development and Evaluation Working Group. Results Five heterogeneous studies, three randomized controlled trials, and two cohort studies form the evidence basis for this report. There was no difference in the incidence of hematoma, superficial wound infection, or deep infection in patients with compared with patients without closed suction wound drains after lumbar surgery. The upper bounds of the 95% confidence interval for hematoma ranged from 1.1 to 16.7%; for superficial infection, 1.0 to 7.3%; and for deep infection, 1.0 to 7.1%. One observational study reported a 3.5-fold increase in the risk of blood transfusion in patients with a drain. The overall strength of evidence for these findings is considered low or insufficient. Conclusions Conclusions from this systematic review are limited by the quality of included studies that assessed the use of closed suction wound drains in lumbar spine surgeries for degenerative conditions. We believe that spine surgeons should not routinely rely on closed suction wound drains in lumbar spine surgery until a higher level of evidence becomes available to support its use. PMID- 26682099 TI - Adverse Event Recording and Reporting in Clinical Trials Comparing Lumbar Disk Replacement with Lumbar Fusion: A Systematic Review. AB - Study Design Systematic review. Objectives (1) To compare the quality of adverse event (AE) methodology and reporting among randomized trials comparing lumbar fusion with lumbar total disk replacement (TDR) using established AE reporting systems; (2) to compare the AEs and reoperations of lumbar spinal fusion with those from lumbar TDR; (3) to make recommendations on how to report AEs in randomized controlled trials (RCTs) so that surgeons and patients have more detailed and comprehensive information when making treatment decisions. Methods A systematic search of PubMed, the Cochrane collaboration database, and the National Guideline Clearinghouse through May 2015 was conducted. Randomized controlled trials with at least 2 years of follow-up comparing lumbar artificial disk replacement with lumbar fusion were included. Patients were required to have axial or mechanical low back pain of >=3 months' duration due to degenerative joint disease defined as degenerative disk disease, facet joint disease, or spondylosis. Outcomes included the quality of AE acquisition methodology and results reporting, and AEs were defined as those secondary to the procedure and reoperations. Individual and pooled relative risks and their 95% confidence intervals comparing lumbar TDR with fusion were calculated. Results RCTs demonstrated a generally poor description of methods for assessing AEs. There was a consistent lack of clear definition or grading for these events. Furthermore, there was a high degree of variation in reporting of surgery-related AEs. Most studies lacked adequate reporting of the timing of AEs, and there were no clear distinctions between acute or chronic AEs. Meta-analysis of the pooled data demonstrated a twofold increased risk of AEs in patients having lumbar fusion compared with patients having lumbar TDR at 2-year follow-up, and this relative risk was maintained at 5 years. Furthermore, the pooled data demonstrated a 1.7 times greater relative risk of reoperation in the fusion group compared with lumbar TDR, although this risk decreased to 1.1 at 5-year follow-up. However, given the lack of quality and consistency in the methods of recording and reporting of AEs, we are unable to make a clear recommendation of one treatment over the other. Conclusions Based on the currently available literature, lumbar TDR appears to be comparable in safety to lumbar fusion. However, due to lack of consistency in reporting of AEs, it is difficult to make conclusions regarding the true safety profile of lumbar TDR. Standardization in AE reporting will significantly improve the reliability of the current literature. PMID- 26682100 TI - Defining the Role of Cognitive Behavioral Therapy in Treating Chronic Low Back Pain: An Overview. AB - Study Design Narrative review of the literature. Objectives Determine if the term cognitive behavioral therapy (CBT) is useful in clinical care and research. What literature supports these variables being relevant to the experience of chronic pain? What effects of CBT in treating these factors have been documented? What methods and platforms are available to administer CBT? Methods Chronic low back pain (CLBP) is a complex neurologic disorder with many components. CBT refers to a broad family of therapies that address both maladaptive thoughts and behaviors. There are several ways to deliver it. CLBP was broken into five categories that affect the perception of pain, and the literature was reviewed to see the effects of CBT on these variables. Results The term cognitive behavioral therapy has little use in future research because it covers such a wide range of therapies. CBT should always be defined by the problem it is intended to solve. The format and method of delivery should be defined because they have implications for outcomes. They are readily available even at the primary care level. The effectiveness of CBT is unquestioned regarding its effectiveness in treating each of the variables that affect CLBP. It is unclear why it is not more widely implemented. Conclusions CBT represents a family of therapies that are effective for a wide range of problems, many of which coexist with and influence CLBP. Each of the variables can be improved with focused CBT. Early, widespread adoption of CBT in treating and preventing CLBP is recommended. Future research and clinical care should focus on strategies to operationalize these well-documented treatments utilizing a public health approach. PMID- 26682101 TI - Nonoperative Management of Craniocervical Ligamentous Distraction Injury: Literature Review. AB - Study Design Literature review and case report. Objective Review the existing literature and report the successful nonoperative management of a two-level craniocervical ligamentous distraction injury. Methods A PubMed and Medline review revealed only three limited reports involving the nonoperative management of patients with craniocervical distraction injury. This article reviews the existing literature and reports the case of a 27-year-old man who was involved in a motorcycle accident and sustained multiple systemic injuries and ligamentous distraction injuries to both occipitocervical joints and both C1-C2 joints. The patient's traumatic brain injury and bilateral pulmonary contusions precluded safe operative management of the two-level craniocervical distraction injury. Therefore, the patient was placed in a halo immobilization device. Results The literature remains unclear as to the specific indications for nonoperative management of ligamentous craniocervical injuries. Nonoperative management was associated with poor outcomes in the majority of reported patients. We report a patient who was managed for 6 months in a halo device. Posttreatment computed tomography and flexion-extension radiographs demonstrated stable occipitocervical and C1-C2 joints bilaterally. The patient reported minimal neck pain and had excellent functional outcome with a Neck Disability Index score of 2 points at 41 months postoperatively. He returned to preinjury level of employment without restriction. Conclusions Further study is needed to determine which craniocervical injuries may be managed successfully with nonoperative measures. PMID- 26682103 TI - Commentary on: "Symptomatic Triple-Region Spinal Stenosis Treated with Simultaneous Surgery: Case Report and Review of the Literature". PMID- 26682102 TI - Symptomatic Triple-Region Spinal Stenosis Treated with Simultaneous Surgery: Case Report and Review of the Literature. AB - Study Design Case report. Objectives Symptomatic triple-region spinal stenosis (TRSS), defined as spinal stenosis in three different regions of the spine, is extremely rare. To our knowledge, treatment with simultaneous decompressive surgery is not described in the literature. We report a case of a patient with TRSS who was treated successfully with simultaneous decompressive surgery in three separate regions of the spine. Methods A 50-year-old man presented with combined progressive cervical and thoracic myelopathy along with severe lumbar spinal claudication and radiculopathy. He underwent simultaneous decompressive surgery in all three regions of his spine and concomitant instrumented fusion in the cervical and thoracic regions. Results Estimated blood loss for the procedure was 600 mL total (250 mL cervical, 250 mL thoracic, 100 mL lumbar) and operative time was ~3.5 hours. No changes were noted on intraoperative monitoring. The postoperative course was uncomplicated. The patient was discharged to inpatient rehabilitation on postoperative day (POD) 7 and discharged home on POD 11. At 6 month follow-up, his gait and motor function was improved and returned to normal in all extremities. He remains partially disabled due to chronic back pain. Conclusions This report is the first of symptomatic TRSS treated with simultaneous surgery in three different regions of the spine. Simultaneous triple region stenosis surgery appears to be an effective treatment option for this rare condition, but may be associated with prolonged hospital stay after surgery. PMID- 26682104 TI - Bullet Fragment of the Lumbar Spine: The Decision Is More Important Than the Incision. AB - Study Design Case report. Objective Treatment of gunshot wounds to the spine is a topic of continued discussion and controversy. The following case study provides a description of a patient with a gunshot wound to the lumbar spine with a retained bullet in the intrathecal space. Methods Immediately after gunshot injury, a patient developed lumbar and radicular pain, as well as neurologic deficits. He was taken for surgery to remove the retained bullet. Results Following surgery, pain and neurologic function improved. The operative techniques and the postoperative clinical management are discussed in this report. Conclusion In our opinion, it was necessary to remove the bullet to avoid migration and possible worsening of neurologic function. However, surgical intervention is not appropriate in every case, and ultimately decisions should be based on patient presentation, symptomology, and imaging. PMID- 26682105 TI - Commentary on: "Bullet Fragment of the Lumbar Spine: The Decision Is More Important Than the Incision". PMID- 26682106 TI - Vertebral Artery Injury during Routine Posterior Cervical Exposure: Case Reports and Review of Literature. AB - Study Design Case series. Objective We report the unusual occurrence of vertebral artery injury (VAI) during routine posterior exposure of the cervical spine. The importance of preoperative planning to identify the course of the bilateral vertebral arteries during routine posterior cervical spine surgery is emphasized. Methods VAI is a rare but potentially devastating complication of cervical spinal surgery. Most reports of VAI are related to anterior surgical exposure or screw placement in the posterior cervical spine. VAI incurred during posterior cervical spinal exposure surgery is not adequately addressed in the existing literature. Two cases of VAI that occurred during routine posterior exposure of the cervical spine in the region of C2 are described. Results VAI was incurred unexpectedly in the region of the midportion of the posterior C1-C2 interval during the initial surgical exposure phase of the operation. An aberrant vertebral artery course in the V2 anatomical section in the region between C1 and C2 intervals was identified postoperatively in both patients. A literature review demonstrates a relatively high incidence of vertebral artery anomalies in the upper cervical spine; however, the literature is deficient in reporting vertebral artery injury in this region. Recommendations for preoperative vertebral artery imaging also remain unclear at this time. Conclusions Successful management of this unexpected complication was achieved in both cases. This case report and review of the literature highlights the importance of preoperative vertebral artery imaging and knowledge of the course of the vertebral arteries prior to planned routine posterior exposure of the upper cervical spine. In both cases, aberrancy of the vertebral artery was present and not investigated or detected preoperatively. PMID- 26682107 TI - Commentary on: "Vertebral Artery Injury during Routine Posterior Cervical Exposure: Case Reports and Review of Literature". PMID- 26682108 TI - Remote Cerebellar Hemorrhage after Revision Lumbar Spine Surgery. AB - Study Design Case report. Objective To report a case of remote cerebellar hemorrhage (RCH) without intraoperative dural tear after revision lumbar spine surgery. RCH is a rare postoperative complication following spine surgery. RCH has previously been reported only in cases with intraoperative dural tear or durotomy. Methods Case report and literature review. Results A 58-year-old woman underwent removal of L4-S1 posterior spinal instrumented fusion (PSIF) implants and L3-L4 decompressive laminectomy with PSIF. There was no intraoperative dural tear. After doing well initially, the patient developed new neurologic symptoms and was found to have RCH. Lumbar spine magnetic resonance imaging (MRI) demonstrated a large dural defect. After repair of the dura, the patient had dramatic improvement of her neurologic symptoms. At 1-year follow-up, the patient continued to have no neurologic sequelae. Conclusion This report demonstrates that RCH can occur without intraoperative dural tear. Although rare, any patient with new onset of declining neurologic symptoms following spine surgery should have a brain MRI and should have RCH on the differential diagnosis. PMID- 26682109 TI - Commentary on: "Remote Cerebellar Hemorrhage after Revision Lumbar Spine Surgery". PMID- 26682110 TI - Definition of levels of evidence (LoE) and overall strength of evidence (SoE). PMID- 26682111 TI - Emotion socialization practices in Italian and Hong Kong-Chinese mothers. AB - BACKGROUND: Parents' emotion socialization practices are their ways of handling their children's emotional experiences in light of cultural expectations surrounding emotions. Such practices are thought to significantly affect children's social adjustment. We compared the parenting practices of Italian and Hong Kong Chinese samples in an ethnological validation study of the maternal responses to children's emotion scale (MRCES). Participants were 71 Italian mothers (M = 39.45) and 71 Hong Kong-Chinese mothers (M = 37.75) with children aged 6-9 years. FINDINGS: The results confirmed the two-factor structure identified by the scale's authors, namely coaching/emotion-encouraging and emotion dismissing approaches, respectively. Each of the two factors displayed satisfactory internal consistency. The Chinese mothers obtained higher scores than the Italian mothers on both subscales. CONCLUSIONS: Our findings suggested that parents' emotion socialization practices for coping with children's emotions received different degrees of emphasis and were underpinned by different meaning in the Hong Kong and Italian cultural groups. These cultural differences are discussed in relation to their effect on children's socio-emotional development. PMID- 26682112 TI - A customer value analysis of Taiwan ice cream market: a means-end chain approach across consumption situations. AB - In the highly competitive market, it is increasingly hard for ice cream stores to develop creative marketing strategies to retain existing customers and attract new ones. This study applies the means-end chain approach to identify the customer value, consequences, and attributes of ice cream and to suggest useful information for ice cream sellers to develop differential marketing strategies across various consumption situations (i.e. on a date, gathering with friends, craving for ice cream). This study conducted one-on-one in-depth interviews with participants. The interview content was subsequently analyzed and coded to produce an implication matrix and a hierarchical value map, which was further used to determine customers' value perceptions. The results indicate the terminal values of the highest strength comprised economy, pleasure, and efficiency. Pleasure was emphasized among consumers who were on a date or gathering with friends, whereas satisfaction was emphasized among consumers who craved ice cream. Based on the results, the study also provides suggestions to the industry and future researchers. PMID- 26682113 TI - Effect of specimen type on free immunoglobulin light chains analysis on the Roche Diagnostics cobas 8000 analyzer. AB - The measurement of free immunoglobulin light chains is typically performed on serum; however, the use of alternative specimen types has potential benefits. Using the FreeliteTM kappa and lambda free light chains assay on a Roche Diagnostics cobas 8000 c502 analyzer, we compared three specimen types (serum, EDTA-plasma and lithium heparin plasma separator gel-plasma) on 100 patients. Using Deming regression and eliminating outliers (limiting data to light chain concentrations below 400 mg/L), the three specimen types showed comparable results for kappa light chain concentration, lambda light chain concentration, and kappa/lambda ratio with slopes close to 1.0 and y-intercepts close to zero. EDTA-plasma showed slightly more positive bias relative to serum than lithium heparin. Analysis using EDTA-plasma and lithium heparin plasma showed comparable linearity, precision, and temperature stability. A single sample showing hook effect (not in the comparison set) gave comparable results using either plasma specimen type. For the FreeliteTM kappa and lambda free light chains assay, both EDTA-plasma or lithium heparin-plasma can serve as acceptable substitutes for serum, at least for the Roche cobas 8000 analyzer. PMID- 26682114 TI - Genetic description of a tick-borne encephalitis virus strain Sofjin with the longest history as a vaccine strain. AB - Vaccines based on the strain Sofjin of the Far-Eastern tick-borne encephalitis virus (TBEV) subtype have been used for TBE prophylaxis for over 50 years in Russia and neighboring countries. On the wide territory, where all known TBEV subtypes are circulating, the cultural, purified, concentrated, inactivated TBE vaccine Moscow has been shown to be safe and efficacious in a massive immunization. In the present work, we describe the genome of the vaccine strain Sofjin. We have shown that it differs from TBEV strains previously published with the name "Sofjin". Moreover, we have shown the stability of the virus during the vaccine manufacturing process on the molecular level. PMID- 26682115 TI - A new logistic-type model for pricing European options. AB - We propose a family of models for the evolution of the price process [Formula: see text] of a financial market. We model share price and volatility using a two dimensional system of stochastic differential equations (SDEs) driven by a single Wiener process. We prove that this family of models is well defined and that each model from this family is free of arbitrage opportunities, and it is (state) complete. We use option prices written over the S&P500 from December 2007 to December 2008 to calibrate a model of the proposed family and compare the calibration results with results of the Heston Model for the same data set. The empirical results achieved in both models show similarities for periods of low volatility, but the model studied shows a better performance during the period of higher volatility. PMID- 26682116 TI - Aggressive NK-cell leukemia in a 69 years old Caucasian woman: a case report. AB - Aggressive NK-cell leukemia is a rare malignancy mostly seen in younger Asians with a rapid clinical course and poor prognosis. Here, we describe a 69 years old Caucasian woman presenting with massive leukemization of neoplastic NK-cells. The cells were abnormal in morphology and surface marker expression and this clearly distinguished them from their normal counterpart. They were large and variable in shapes with irregular folding of the nuclei. By flow cytometry, their light scatter characteristics resembled normal monocytes. They showed bright expression of CD56 and CD2 but markedly decreased expression of CD7. They also expressed CD25. The patient presented with general malaise, including high fever, abdominal pain, signs and haemophagocytosis, and she quickly deteriorated and died 11 days after hospitalization. The origin of the leukemic cells of aggressive NK-cell leukemia is most likely the relatively scarce population of CD56(bright) NK cells, primarily residing lymph nodes and tonsils. The immunophenotype of the case presented here support this, adding CD25 expression which is not earlier addressed in this entity. PMID- 26682117 TI - Impact of a CBT psychotherapy group on post-operative bariatric patients. AB - Psychological difficulties for patients seeking bariatric surgery are greater and in the post-operative phase, a significant minority go on to experience significant psychosocial difficulties, increasing their risk of poorer post operative adjustment and associated weight regain. 17 post-operative patients participated in an eight-week cognitive behavioral therapy (CBT) based psychotherapy group at the Ottawa Hospital. A pre-post design with a 3-month follow-up investigated the impact of the group on emotional eating, general as well as obesity-specific adjustment, psychological distress, and attachment. There were significant and meaningful improvements in patients' level of psychological distress, perceived difficulties in their lives, and weight-related adjustment that were maintained at a 3-month follow-up period. Although statistical change was not significant, there were also meaningful improvements in emotional overeating and relationship anxiety and avoidance. The intervention also appeared to be acceptable to patients in that attendance and satisfaction were good. Findings suggest that a short-term CBT psychotherapy group led to significant and meaningful benefits in psychological wellbeing for post-surgical bariatric patients. PMID- 26682118 TI - The Incidence of Early Postoperative Conductive Hearing Loss after Microvascular Decompression of Hemifacial Spasm. AB - Objectives To evaluate the incidence and discuss the pathogenesis of early postoperative conductive hearing loss (CHL) after microvascular decompression (MVD) for hemifacial spasm (HFS). Design Pre- and postoperative audiogram data and brainstem auditory evoked potentials (BAEPs) from patients who had underwent MVD for HFS were analyzed. Setting The study was conducted at the University of Pittsburgh Medical Center. Participants MVD for HFS patients who had pre- and postoperative audiogram data, BAEP data, and normal structure of the external and middle ear were included in the study. Main Outcome Measures CHL was diagnosed if there was an air-bone gap in pure tone audiometry of at least 10 dB at 0.5, 1, 2, or 4 kHz. Results The incidence of early postoperative CHL in the ipsilateral ear was 18.7% postoperatively. No CHL was observed in the contralateral side. No significant relationship between CHL and intraoperative BAEP changes was found. Demographic parameters were not significantly different between groups with and without CHL. Conclusions Early postoperative CHL is a significant complication after MVD. Fluid entering the mastoid air cells and/or bone-dust deposition during craniotomy may result in CHL. Long-term audiograms will be needed to evaluate the risk factors that lead to permanent CHL. PMID- 26682119 TI - Grading Facial Nerve Function Following Combined Static and Mimetic Surgical Techniques. AB - Objective To present a grading scale to assess the functional recovery of the facial nerve in patients who have undergone mimetic and static surgical techniques for facial reanimation. Study design This is a proposed new facial nerve grading system that will be demonstrated with specific case presentations. All patients underwent a variety of neural grafting, microvascular free-flap reconstruction, or surgical static procedures. Results The proposed facial nerve grading scale is one that has not been described previously in the literature and is applicable to a unique patient population. Its ease of use in this patient population will allow otolaryngologists to assess facial recovery accurately and quickly in cases where the facial nerve is not anatomically intact. Conclusion The proposed facial recovery grading scale provides an efficient means of grading facial recovery for a unique group of patients who previously could not be followed. The proposed scale is practical and easy to use in a clinical setting. PMID- 26682120 TI - Clinical Characteristics of Posterior and Lateral Semicircular Canal Dehiscence. AB - The objective of this study was to evaluate the characteristic symptoms of and treatments for lateral semicircular canal dehiscence (LSCD) and posterior semicircular canal dehiscence (PSCD) and its proposed mechanism. A dehiscence acquired in any of the semicircular canals may evoke various auditory symptoms (autophony and inner ear conductive hearing loss) or vestibular symptoms (vertigo, the Tullio phenomenon, and Hennebert sign) by creating a "third mobile window" in the bone that enables aberrant communication between the inner ear and nearby structures. A PubMed search was performed using the keywords lateral, posterior, and semicircular canal dehiscence to identify all relevant cases. Our data suggest that PSCD, although clinically rare, is most likely associated with a high-riding jugular bulb and fibrous dysplasia. Patients may experience auditory manifestations that range from mild conductive to extensive sensorineural hearing loss. LSCD is usually associated with chronic otitis media with cholesteatoma. PMID- 26682121 TI - Easy and Safe Method for Facial Nerve Identification in Parotid Surgery. AB - Background A safe and easy anatomical landmark is proposed to identify the facial nerve in parotid surgery. The facial nerve forms the center point between the base of the styloid process and the origin of the posterior belly of the digastric muscle. Objective To evaluate the consistency, accuracy, and safety of the landmark in identifying the facial nerve. Methods The study was designed in three steps: a cadaver study, a radiologic study, and a prospective clinical study. Anatomy was initially studied in two cadavers. Then the images of 200 temporal styloid regions were studied for consistency of the presence of the styloid base. In the second part of the radiologic study, the distance between the styloid base and the origin of the posterior belly of the digastric muscle was studied in 50 parotid regions. The clinical study involved 25 patients who underwent parotidectomy. Results The styloid base was present in all the images studied. The mean distance between the styloid base and the origin of the posterior belly of the digastric was found to be 0.72 cm (range: 0.45-0.99 cm). The facial nerve could be identified consistently and safely in all patients. Conclusion This trident landmark provided safe, accurate, and easy identification of the facial nerve using two fixed bony landmarks. PMID- 26682122 TI - The Reverse-Flow Facial Artery Buccinator Flap for Skull Base Reconstruction: Key Anatomical and Technical Considerations. AB - Objective To highlight key anatomical and technical considerations for facial artery identification, and harvest and transposition of the facial artery buccinator (FAB) flap to facilitate its future use in anterior skull base reconstruction. Only a few studies have evaluated the reverse-flow FAB flap for skull base defects. Design Eight FAB flaps were raised in four cadaveric heads and divided into thirds; the facial artery's course at the superior and inferior borders of the flap was measured noting in which incisional third of the flap it laid. The flap's reach to the anterior cranial fossa, sella turcica, clival recess, and contralateral cribriform plate were studied. A clinical case and operative video are also presented. Results The facial artery had a near vertical course and stayed with the middle (5/8) or posterior third (3/8) of the flap in the inferior and superior incisions. Seven of eight flaps covered the sellar/planar regions. Only four of eight flaps covered the contralateral cribriform region. Lastly, none reached the middle third of the clivus. Conclusions The FAB flap requires an understanding of the facial artery's course, generally seen in the middle third of the flap, and is an appropriate alternative for sellar/planar and ipsilateral cribriform defects. PMID- 26682123 TI - Variability of the Middle Meningeal Artery Subject to the Shape of Skull. AB - Objectives Endovascular embolization of the middle meningeal artery (MMA) is currently considered one of the basic methods to treat acute bleeding and a posttraumatic aneurysm. The present research correlates the morphological characteristics of the MMA with individual skull shape. Design A prospective cohort study. Setting Hospital of University of Jordan (Amman, Jordan) from 2012 to 2013. Participants A total of 50 patients without known vascular pathology in the carotid system underwent routine magnetic resonance angiography examination of the head and neck. Main Outcome Measures The length and outer diameter of extracranial, intraosseous, and intracranial segments of the MMA were measured in patients with dolichocephalic, mesocephalic, and brachycephalic types of skulls. Results The brachycephalic patients have the most inauspicious anatomical precondition for endovascular intervention of the MMA due to the narrowest lumen of the vessel, high probability of a tortuous extracranial part, and pronounced inflexion at the transmission of the intraosseous segment to the intracranial one. Conclusions The morphological characteristics of the MMA have a close correlation with individual skull shape. PMID- 26682124 TI - Modified One-piece Supraorbital Approach for Orbital Tumors: Widely Preserved Orbital Roof in a Self-fitting Flap. AB - Objectives The one-piece supraorbital approach is a rational approach for the removal of orbital tumors. However, cutting the roof through the orbit is often difficult. We modified the technique to facilitate the osteotomy and improve the cosmetic effect. Design Three burr holes are made: the first, the MacCarty keyhole (burr hole 1), exposes the anterior cranial fossa and orbit; the second is placed above the supraorbital nerve (burr hole 2); and the third on the superior temporal line. Through burr hole 2, a small hole is created on the roof, 10 mm in depth. Next the roof is rongeured through burr hole 1 toward the preexisting small hole. Seamless osteotomies using a diamond-coated threadwire saw and the preexisting four holes are performed. Lastly the flap is removed. On closure, sutures are passed through holes in the cuts made with the threadwire saw, and tied. Results We applied our technique to address orbital tumors in two adult patients. The osteotomies in the roof were easy, and most parts of the roof were repositioned. Conclusions Our modification results in orbital osteotomies with greater preservation of the roof. Because the self-fitting flap does not require the use of fixation devices, the reconstruction is cosmetically satisfactory. PMID- 26682125 TI - The Olfactory Strip and Its Preservation in Endoscopic Pituitary Surgery Maintains Smell and Sinonasal Function. AB - Background The return of olfaction and of sinonasal function are important end points after pituitary surgery. Opinions differ on the impact of surgery because techniques vary greatly. A modified preservation of the so-called olfactory strip is described that utilizes a small nasoseptal flap and wide exposure. Methods A cohort of patients undergoing pituitary surgery and endoscopic sinonasal tumor surgery were assessed. Patient-reported outcomes (Sino-Nasal Outcome Test [SNOT22] and Nasal Symptom Score [NSS]) were recorded. A global score of sinonasal function and the impact on smell and taste were obtained. Objective smell discrimination testing was performed in the pituitary group with the Smell Identification Test. Outcomes were assessed at baseline and at 6 months. Results Ninety-eight patients, n = 40 pituitary (50.95 +/- 15.31 years; 47.5% female) and n = 58 tumor (52.35 +/- 18.51 years; 52.5% female) were assessed. For pituitary patients, NSSs were not significantly different pre- and postsurgery (2.75 +/- 3.40 versus 3.05 +/- 3.03; p = 0.53). SNOT22 scores improved postsurgery (1.02 +/ 0.80 versus 0.83 +/- 0.70; p = 0.046). Objective smell discrimination scores between baseline and 6 months were similar (31.63 +/- 3.49 versus 31.35 +/- 4.61; p = 0.68). No difference in change of olfaction was seen compared with controls (Kendall tau-b p = 0.46). Conclusions Preservation of the olfactory strip can provide a low morbidity approach without adversely affecting olfaction and maintaining reconstruction options. PMID- 26682126 TI - The Prevalence of High-Riding Jugular Bulb in Patients with Suspected Endolymphatic Hydrops. AB - Background To determine the prevalence of a high-riding jugular bulb (HRJB) in the endolymphatic hydrops population. Methods This was a retrospective chart and radiology review of patients seen at a tertiary care medical center. Patients were identified using the International Classification of Diseases, 9th edition, code 386.xx (Meniere disease-unspecified), and were required to have undergone an imaging study that included views of the jugular bulb that were available for review. A radiologist then evaluated all of the imaging studies for evidence of HRJB or inner ear dehiscence with a jugular bulb abnormality. Results The prevalence of a HRJB in all endolymphatic hydrops patients was 9.0% (7 of 78), and it was 4.5% (7 of 156) in all ears. The prevalence of HRJB ipsilateral to an ear with endolymphatic hydrops was 4.6% (4 of 88 ears); it was 4.4% (3 of 68 ears) in ears without endolymphatic hydrops. The incidence of inner ear dehiscence with a HRJB was 1.3% (1 of 78). Electrocochleography results were not correlated with jugular bulb volume. Discussion The results of this study indicate that a small subset of patients treated for endolymphatic hydrops patients have a HRJB. Overall, these results suggest that HRJB does not play a major role in endolymphatic hydrops, although it may play a role in a few isolated patients. PMID- 26682127 TI - Surgical Management of Intracranial Neuroenteric Cysts: The UCSF Experience. AB - Objective Modern surgical experience with intracranial neuroenteric cysts is limited in the literature. We review our 15-year institutional experience with these rare lesions. Design Single-institution retrospective study. Setting Large North American tertiary care center. Participants Histologically confirmed cases of intracranial neuroenteric cyst from January 2000 to September 2014. Main Outcome Measures Pre- and postoperative modified Rankin Scale (mRS) scores, extent of resection, and postoperative complications are reported. Clinical presentation, imaging features, pathology, and operative approach are discussed. Results Five spinal and six intracranial neuroenteric cysts were surgically treated over a 15-year period. Median age at presentation for the intracranial cysts was 38.5 years. Mean cyst diameter was 3.8 cm. Five cysts were located in the pre-pontomedullary cistern, and one was located in the third ventricle. Gross total resection was achieved in four of the five posterior fossa cysts through a far lateral transcondylar approach. Postoperative complications included aseptic meningitis (one), transient abducens palsy (one), and pseudomeningocele requiring reoperation (three). Postoperative mRS scores improved to <=1 by 6.5 months median follow-up. Conclusions Intracranial neuroenteric cysts are rare lesions with a variable imaging appearance. Complete surgical resection through a far lateral transcondylar approach is possible and usually results in symptom improvement or resolution. PMID- 26682129 TI - Nosocomial oral myiasis in ICU patients: occurrence of three sequential cases. AB - Myiasis is the infestation of living vertebrates or humans tissues by dipterous larvae. The oral cavity is rarely affected by this infestation and the circumstances which can lead to oral myiasis include persistent mouth opening together with poor hygiene. Such infestations have been reported mainly in developing countries such as in Asia. Although rare, nosocomial myiasis must be noted carefully, especially in case of hospitalized patients. This report describes three cases of nosocomial oral myiasis in hospitalized patients in ICU (intensive care unit) in Tabriz, North West of Iran. PMID- 26682128 TI - Endoscopic Endonasal Approaches to the Craniovertebral Junction: A Systematic Review of the Literature. AB - Background We reviewed the current literature pertaining to extended endoscopic endonasal approaches to the craniovertebral junction. Methods A systematic literature review was utilized to identify published surgical cases of endoscopic endonasal approaches to the craniovertebral junction. Full-text manuscripts were examined for various measures of surgical indications, patient characteristics, operative technique, and surgical outcomes. Results We identified 71 cases involving endoscopic endonasal approaches for surgical management of a variety of pathologies located within the craniovertebral junction. Patient ages ranged from 3 to 87 years, with 40 females and 31 males. Five patients required tracheostomy, two were reintubated, and all others experienced an average intubation duration of 0.54 days following surgery. Fifty-eight patients (81.7%) underwent an additional posterior decompression or fusion either before or after the endonasal procedure. A complete resection of the pathologic lesion was reported in 57 cases (83.8%), another five were successful biopsies, and four resulted in partial resection. The follow-up time ranged from 0.5 to 57 months. Conclusion Although the transoral approach has been the standard for anterior surgical management for the past several decades, our systematic review illustrates that the extended endoscopic endonasal approach is a safe and effective alternative for most pathologies affecting the craniovertebral junction. PMID- 26682131 TI - The Barriers to Mental Health Services Scale Revised: Psychometric Analysis Among Older Adults. AB - OBJECTIVES: Older adults underutilize mental health services suggesting that significant barriers are operating. This study presents reliability and validity data for a revised version of the self-report Barriers to Mental Health Services Scale (BMHSS) designed to quantify 10 barriers to mental health service use, so that barriers can be examined collectively. METHODS: The Barriers to Mental Health Services Scale Revised (BMHSS-R) was revised to improve its reliability and validity, including adding items, eliminating poor items, and balancing the number of items across subscales. A sample of 100 older adults (M age = 72.1 years, SD = 17.8 years) completed the BMHSS-R, the Beliefs Toward Mental Illness Scale, and the Willingness to Seek Help Questionnaire. RESULTS: Internal consistency for the 10 subscales of the BMHSS-R ranged between .63 and .87, with 8 of the 10 values greater than .70. Correlational analyses indicated that many of the subscales overlap considerably but are still distinct. Convergent validity of the BMHSS-R subscales of help-seeking and stigma was partially supported, although correlations were modest. CONCLUSION: Revisions to the BMHSS resulted in improved reliability estimates for use as a measure of perceived barriers to mental health services. We recommend when using the BMHSS-R to combine results with other information (e.g., service utilization data) to characterize a profile of barriers. We discuss directions for future research and further refinement of the BMHSS-R. PMID- 26682132 TI - Are GIS-modelled routes a useful proxy for the actual routes followed by commuters? AB - Active commuting offers the potential to increase physical activity among adults by being built into daily routines. Characteristics of the route to work may influence propensity to walk or cycle. Geographic information system (GIS) software is often used to explore this by modelling routes between home and work. However, if the validity of modelled routes depends on the mode of travel used, studies of environmental determinants of travel may be biased. We aimed to understand how well modelled routes reflect those actually taken, and what characteristics explain these differences. We compared modelled GIS shortest path routes with actual routes measured using QStarz BT-Q1000X Global Positioning System (GPS) devices in a free-living sample of adults working in Cambridge and using varying travel modes. Predictors of differences, according to length and percentage overlap, between the two route sets were assessed using multilevel regression models and concordance coefficients. The 276 trips, made by 51 participants, were on average 27% further than modelled routes, with an average geographical overlap of 39%. However, predictability of the route depended on travel mode. For route length, there was moderate-to-substantial agreement for journeys made on foot and by bicycle. Route overlap was lowest for trips made by car plus walk (22%). The magnitude of difference depended on other journey characteristics, including travelling via intermediate destinations, distance, and use of busy roads. In conclusion, GIS routes may be acceptable for distance estimation and to explore potential routes, particularly active commuting. However, GPS should be used to obtain accurate estimates of environmental contexts in which commuting behaviour actually occurs. Public health researchers should bear these considerations in mind when studying the geographical determinants and health implications of commuting behaviour, and when recommending policy changes to encourage active travel. PMID- 26682133 TI - Recent advances in surgical planning & navigation for tumor biopsy and resection. AB - This paper highlights recent advancements in imaging technologies for surgical planning and navigation in tumor biopsy and resection which need high-precision in detection and characterization of lesion margin in preoperative planning and intraoperative navigation. Multimodality image-guided surgery platforms brought great benefits in surgical planning and operation accuracy via registration of various data sets with information on morphology [X-ray, magnetic resonance (MR), computed tomography (CT)], function connectivity [functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), rest-status fMRI], or molecular activity [positron emission tomography (PET)]. These image-guided platforms provide a correspondence between the pre-operative surgical planning and intra operative procedure. We envisage that the combination of advanced multimodal imaging, three-dimensional (3D) printing, and cloud computing will play increasingly important roles in planning and navigation of surgery for tumor biopsy and resection in the coming years. PMID- 26682134 TI - Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes. AB - BACKGROUND: The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients. METHODS: From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test. RESULTS: Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57). CONCLUSIONS: Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery. PMID- 26682135 TI - Theranostic nanoparticles for enzyme-activatable fluorescence imaging and photodynamic/chemo dual therapy of triple-negative breast cancer. AB - BACKGROUND: Triple-negative breast cancer (TNBC) is a highly diverse group of cancers characterized by tumors that does not express estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2 (HER2) gene expression. TNBC is associated with poor prognosis due to high rate of recurrence and distance metastasis, lack of response to hormonal or HER2-targeted therapies, and partial response to chemotherapy. Hence, development of new therapeutic strategies to overcome such limitations is of great importance. Here we describe the application of photosensitizer-conjugated and camptothecin (CPT)-encapsulated hyaluronic acid (HA) nanoparticles as enzyme-activatable theranostic nanoparticles (EATNP) for near-infrared (NIR) fluorescence imaging and photodynamic/chemo dual therapy of TNBC. METHODS: For the preparation of EATNPs, chlorin e6 (Ce6), a second generation photosensitizer, was covalently conjugated to a monomethoxy poly(ethylene glycol)-grafted HA backbone. Ce6-conjugated HA (Ce6-HA) formed self-assembled nanoparticles (i.e., Ce6-HA NPs) in an aqueous solution. Subsequently, CPT, a topoisomerase 1 inhibitor with remarkable anticancer efficacy but with low water solubility, was encapsulated inside the hydrophobic core of Ce6-HA NPs thereby forming EATNPs. RESULTS: Fluorescence and singlet oxygen generation (SOG) of EATNPs are quenched in its native state. Treatment of EATNPs with hyaluronidase (HAdase) induces enzyme concentration dependent activation of NIR fluorescence and SOG. Moreover, HAdase-mediated degradation of the nanoparticles also triggers the release of CPT from the EATNPs. In vitro confocal microscopy and cytotoxicity tests confirmed that EATNPs were efficiently introduced into MDA-MB-231 TNBC cell line, thereby inducing better cytotoxicity than that by free CPT. Additional light irradiation onto the EATNP-treated cells significantly increased therapeutic efficacy in TNBC, which indicates that EATNP plays an important role in enzyme-activated NIR fluorescence imaging and photodynamic/chemo dual therapy of TNBC. CONCLUSIONS: We found that HAdase may switch on NIR fluorescence and SOG of EATNPs. Moreover, CTP release from the nanoparticles is triggered by the enzyme HAdase. In vitro cell study showed potential utility of EATNPs for fluorescence imaging and photodynamic/chemo dual therapy of TNBC. PMID- 26682136 TI - Daily patient setup error in prostate image guided radiation therapy with fiducial-based kilovoltage onboard imaging and conebeam computed tomography. AB - BACKGROUND: This study examined the interfraction setup error in patients undergoing prostate radiotherapy using fiducial markers and on-board imaging. METHODS: Patients (n=53) were aligned to the treatment isocenter by laser followed by orthogonal kilovoltage (kV) radiographs to visualize bony anatomy and implanted fiducial markers. The magnitude and direction of couch shifts for isocenter correction required was determined by image registration for bony anatomy and fiducial markers. Twice weekly, 25 of the 53 patients also underwent conebeam computed tomography (CBCT) to measure any residual error in patient positioning. Based on individual coordinate shifts from CBCT, a net three dimensional (3D) residual shift magnitude vector R was calculated. RESULTS: The average couch shifts were 0.26 and 0.40 cm in inferior direction and 0.25 and 0.33 cm in superior direction for alignments made with bony anatomy and fiducial markers, respectively (P<0.0001). There were no significant differences noted in the vertical or lateral planes between the two image registration methods. In subset of 25 patients, no residual shift from fiducial plain film set up was required with CBCT matching in 66.5%, 52.4% and 57.9% of fractions for longitudinal, vertical and lateral planes, respectively, with majority (79%) of patients having a net residual 3D shifts of <0.3 cm. The use of CBCT increased average treatment time by approximately 6 min compared to kV radiographs alone. CONCLUSIONS: The residual setup errors following daily kV image guided localization, as determined by CBCT, were small, which demonstrates high accuracy of kV localization when fiducial markers are present. PMID- 26682137 TI - Quantitative radiology: automated measurement of polyp volume in computed tomography colonography using Hessian matrix-based shape extraction and volume growing. AB - BACKGROUND: Current measurement of the single longest dimension of a polyp is subjective and has variations among radiologists. Our purpose was to develop a computerized measurement of polyp volume in computed tomography colonography (CTC). METHODS: We developed a 3D automated scheme for measuring polyp volume at CTC. Our scheme consisted of segmentation of colon wall to confine polyp segmentation to the colon wall, extraction of a highly polyp-like seed region based on the Hessian matrix, a 3D volume growing technique under the minimum surface expansion criterion for segmentation of polyps, and sub-voxel refinement and surface smoothing for obtaining a smooth polyp surface. Our database consisted of 30 polyp views (15 polyps) in CTC scans from 13 patients. Each patient was scanned in the supine and prone positions. Polyp sizes measured in optical colonoscopy (OC) ranged from 6-18 mm with a mean of 10 mm. A radiologist outlined polyps in each slice and calculated volumes by summation of volumes in each slice. The measurement study was repeated 3 times at least 1 week apart for minimizing a memory effect bias. We used the mean volume of the three studies as "gold standard". RESULTS: Our measurement scheme yielded a mean polyp volume of 0.38 cc (range, 0.15-1.24 cc), whereas a mean "gold standard" manual volume was 0.40 cc (range, 0.15-1.08 cc). The "gold-standard" manual and computer volumetric reached excellent agreement (intra-class correlation coefficient =0.80), with no statistically significant difference [P (F<=f) =0.42]. CONCLUSIONS: We developed an automated scheme for measuring polyp volume at CTC based on Hessian matrix based shape extraction and volume growing. Polyp volumes obtained by our automated scheme agreed excellently with "gold standard" manual volumes. Our fully automated scheme can efficiently provide accurate polyp volumes for radiologists; thus, it would help radiologists improve the accuracy and efficiency of polyp volume measurements in CTC. PMID- 26682138 TI - Peak flow velocities in the ascending aorta-real-time phase-contrast magnetic resonance imaging vs. cine magnetic resonance imaging and echocardiography. AB - This prospective study of eight healthy volunteers evaluates peak flow velocities (PFV) in the ascending aorta using real-time phase-contrast magnetic resonance imaging (MRI) in comparison to cine phase-contrast MRI and echocardiography. Flow measurements by echocardiography and cine phase-contrast MRI with breath-holding were performed according to clinical standards. Real-time phase-contrast MRI at 40 ms temporal resolution and 1.3 mm in-plane resolution was based on highly undersampled radial fast low-angle shot (FLASH) sequences with image reconstruction by regularized nonlinear inversion (NLINV). Evaluations focused on the determination of PFV. Linear regressions and Bland-Altman plots were used for comparisons of methods. When averaged across subjects, real-time phase-contrast MRI resulted in PFV of 120+/-20 cm s(-1) (mean +/- SD) in comparison to 122+/-16 cm s(-1) for cine MRI and 124+/-20 cm s(-1) for echocardiography. The maximum deviations between real-time phase-contrast MRI and echocardiography ranged from 20 to +14 cm s(-1) (cine MRI: -10 to +12 cm s(-1)). Thus, in general, real-time phase-contrast MRI of cardiac outflow revealed quantitative agreement with cine MRI and echocardiography. The advantages of real-time MRI are measurements during free breathing and access to individual cardiac cycles. PMID- 26682139 TI - Comparison between computed tomography multislice and high-field magnetic resonance in the diagnostic evaluation of patients with renal masses. AB - BACKGROUND: Renal masses are a common finding in diagnostic imaging; these lesions usually are solid or cystic, benign or malignant, and the correct diagnosis may be difficult. The aim of our study was the comparison of multi slice computed tomography (MSCT) and high-field magnetic resonance (MR) in the diagnostic evaluation of renal masses. METHODS: We studied 29 patients, 16 men and 13 women aged 8-85 years (mean 61+/-17 years) with histo-cytological diagnosis of renal masses (n=31), of which the majority (74%; n=23) was represented by malignant lesions [renal cell carcinoma (Ca) =16, chromophobe renal cell Ca =2, squamous cell Ca =1, urothelial Ca =2, lymphoma =1, Wilms tumor =1]; the remaining 8 masses (26%) were benign (pyelonephritis =2, simple cyst =1, hematic cyst =1, lipoma =1 and oncocytoma =3). All patients underwent MSCT and MR (3.0 Tesla) before and after contrast injection; the images were evaluated in double-blind by two expert radiologists. The results of the images were then compared with the histo-cytological data to calculate the values of diagnostic accuracy for both methods in the identification and characterization of renal masses. The benign or malignant nature of the lesions was established according to the regularity of the margins, presence or absence of significant contrast enhancement, infiltration of perirenal fat and vascular invasion. The concordance of the results of the two imaging techniques was then calculated using the coefficient Kappa Cohen. RESULTS: For both identification and characterization of renal masses, MSCT and MR showed comparable values of diagnostic accuracy with a significant concordance (k=1); in particular, the diagnostic accuracy of MSCT/MR was 100%/100% for lesion identification, 90%/90% for lesion characterization in terms of benign or malignant nature, 97%/97% for the evaluation of lesion edges, 90%/90% for the assessment of lesion contrast enhancement, 93%/93% for the evaluation of peri-renal fat infiltration and 96%/96% for the evaluation of vascular infiltration. Only in three cases of oncocytoma the two imaging methods were both inaccurate for diagnosis of benignity classifying the lesions as probably malignant on the basis of the absence of central scar and of dynamic contrast enhancement pattern. CONCLUSIONS: The results of our study show comparable diagnostic accuracy of computed tomography (CT) and MR for the identification and characterization of expansive renal lesions. High-field MR is, therefore, a valid alternative to MSCT in the evaluation of renal masses avoiding exposure to ionizing radiation. PMID- 26682140 TI - Impacts of biological and procedural factors on semiquantification uptake value of liver in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging. AB - BACKGROUND: Increased metabolic activity of fluorodeoxyglucose (FDG) in tissue is not only resulting of pathological uptake, but due to physiological uptake as well. This study aimed to determine the impacts of biological and procedural factors on FDG uptake of liver in whole body positron emission tomography/computed tomography (PET/CT) imaging. METHODS: Whole body fluorine-18 ((18)F) FDG PET/CT scans of 51 oncology patients have been reviewed. Maximum standardized uptake value (SUVmax) of lesion-free liver was quantified in each patient. Pearson correlation was performed to determine the association between the factors of age, body mass index (BMI), blood glucose level, FDG dose and incubation period and liver SUVmax. Multivariate regression analysis was established to determine the significant factors that best predicted the liver SUVmax. Then the subjects were dichotomised into four BMI groups. Analysis of variance (ANOVA) was established for mean difference of SUVmax of liver between those BMI groups. RESULTS: BMI and incubation period were significantly associated with liver SUVmax. These factors were accounted for 29.6% of the liver SUVmax variance. Statistically significant differences were observed in the mean SUVmax of liver among those BMI groups (P<0.05). CONCLUSIONS: BMI and incubation period are significant factors affecting physiological FDG uptake of liver. It would be recommended to employ different cut-off value for physiological liver SUVmax as a reference standard for different BMI of patients in PET/CT interpretation and use a standard protocol for incubation period of patient to reduce variation in physiological FDG uptake of liver in PET/CT study. PMID- 26682142 TI - Preoperative portal vein embolization in liver cancer: indications, techniques and outcomes. AB - Postoperative liver failure is a severe complication of major hepatectomies, in particular in patients with a chronic underlying liver disease. Portal vein embolization (PVE) is an approach that is gaining increasing acceptance in the preoperative treatment of selected patients prior to major hepatic resection. Induction of selective hypertrophy of the non-diseased portion of the liver with PVE in patients with either primary or secondary hepatobiliary, malignancy with small estimated future liver remnants (FLR) may result in fewer complications and shorter hospital stays following resection. Additionally, PVE performed in patients initially considered unsuitable for resection due to lack of sufficient remaining normal parenchyma may add to the pool of candidates for surgical treatment. A thorough knowledge of hepatic segmentation and portal venous anatomy is essential before performing PVE. In addition, the indications and contraindications for PVE, the methods for assessing hepatic lobar hypertrophy, the means of determining optimal timing of resection, and the possible complications of PVE need to be fully understood before undertaking the procedure. Technique may vary among operators, but cyanoacrylate glue seems to be the best embolic agent with the highest expected rate of liver regeneration for PVE. The procedure is usually indicated when the remnant liver accounts for less than 25-40% of the total liver volume. Compensatory hypertrophy of the non embolized segments is maximal during the first 2 weeks and persists, although to a lesser extent during approximately 6 weeks. Liver resection is performed 2 to 6 weeks after embolization. The goal of this article is to discuss the rationale, indications, techniques and outcomes of PVE before major hepatectomy. PMID- 26682141 TI - Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research. AB - Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-specific property. Chemical carcinogens can be classified upon their origins such as environmental pollutants, cooked meat derived carcinogens, N-nitroso compounds, food additives, antineoplastic agents, naturally occurring substances and synthetic carcinogens, etc. Carcinogen-induced models of primary cancers can be used to evaluate the diagnostic/therapeutic effects of candidate drugs, investigate the biological influential factors, explore preventive measures for carcinogenicity, and better understand molecular mechanisms involved in tumor initiation, promotion and progression. Among commonly adopted cancer models, chemically induced primary malignancies in mammals have several advantages including the easy procedures, fruitful tumor generation and high analogy to clinical human primary cancers. However, in addition to the time-consuming process, the major drawback of chemical carcinogenesis for translational research is the difficulty in noninvasive tumor burden assessment in small animals. Like human cancers, tumors occur unpredictably also among animals in terms of timing, location and the number of lesions. Thanks to the availability of magnetic resonance imaging (MRI) with various advantages such as ionizing-free scanning, superb soft tissue contrast, multi-parametric information, and utility of diverse contrast agents, now a workable solution to this bottleneck problem is to apply MRI for noninvasive detection, diagnosis and therapeutic monitoring on those otherwise uncontrollable animal models with primary cancers. Moreover, it is foreseeable that the combined use of chemically induced primary cancer models and molecular imaging techniques may help to develop new anticancer diagnostics and therapeutics. PMID- 26682143 TI - Diffusion-weighted imaging in musculoskeletal radiology-clinical applications and future directions. AB - Diffusion-weighted imaging (DWI) is an established diagnostic tool with regards to the central nervous system (CNS) and research into its application in the musculoskeletal system has been growing. It has been shown that DWI has utility in differentiating vertebral compression fractures from malignant ones, assessing partial and complete tears of the anterior cruciate ligament (ACL), monitoring tumor response to therapy, and characterization of soft-tissue and bone tumors. DWI is however less useful in differentiating malignant vs. infectious processes. As of yet, no definitive qualitative or quantitative properties have been established due to reasons ranging from variability in acquisition protocols to overlapping imaging characteristics. Even with these limitations, DWI can still provide clinically useful information, increasing diagnostic accuracy and improving patient management when magnetic resonance imaging (MRI) findings are inconclusive. The purpose of this article is to summarize recent research into DWI applications in the musculoskeletal system. PMID- 26682145 TI - AME survey-003 A1-part1: in current China, do you regret you joined the medical profession. AB - BACKGROUND: The medical workforce constitutes the foundation of the provision of health services in all countries. The effectiveness of health systems and the quality of health services are directly related to the performance of health workers. Satisfaction level of the job affects the quality of care for patients. An anonymous on-line survey was conducted with the aim to obtain a better understanding of the current morale of Chinese medical professionals. METHODS: An online cross-sectional questionnaire based survey was conducted during the period of Sep 10-23, 2015, via the platform provided by DXY (www.dxy.cn), which is the largest medical and paramedical related website in China. In addition to demographics of the participants, a particular question was asked to the participants, in current China do you regret you joined the medical profession? This initial report analyzed the relationship between the participants with 'No' or 'Yes' answers to their demographic characteristics. RESULTS: In total 2,356 DXY users completed the survey, including 1,740 males (73.82%) and 617 females (26.18%), with a mean age of 31.96+/-7.03 yrs. There were more participants from relatively economically developed eastern coast areas. The N/Y (no regret participants vs. regretted participants ratio) ratio for all participants was 1.06 (P=0.181). The N/Y ratio of males and females was 1.04 and 1.11 respectively, and there was no significant difference in this ratio among them. There were 1,549 participants from IIIA hospitals (65.72%, N/Y ratio =1.15, P=0.008), followed by IIIB & IIA hospitals (25.46%, N/Y ratio =0.87, P=0.086), IIB & II C hospitals (3.7%, N/Y ratio =0.83, P=0.394), and lastly 1A & 1B clinics (2.6%, N/Y ratio =1.35, P=0.249). A total of 1,323 participants (56.13%) were trainee doctors with N/Y ratio of 1.19 (P=0.002), followed by lecturer-level attending specialists (27.79%, N/Y ratio =0.81, P=0.009), associate principle doctors (12.43%, N/Y ratio =1.01, P=0.953), and lastly principle doctors (3.73%, N/Y ratio =1.59, P=0.033). Specialties with less stressful workload such as radiology and traditional Chinese medicine have the highest job satisfaction, while doctors in accident and emergency cluster have the least job satisfaction. Medical professionals from Yunnan, Gansu and Shanxi have relatively higher positive response (higher N/Y ratio), despite the fact that these are not the economically advanced regions in China; while Jiangsu, an economically advanced province, had relatively higher negative response (lower N/Y ratio). CONCLUSIONS: The morale of majority medical professional in China mainland is likely to be positive. Job satisfaction is inversely related to work related stress level, but may not related to the absolute income. PMID- 26682144 TI - Current role of multiparametric magnetic resonance imaging for prostate cancer. AB - Multiparametric magnetic resonance imaging (mp-MRI) has shown promising results in diagnosis, localization, risk stratification and staging of clinically significant prostate cancer, and targeting or guiding prostate biopsy. mp-MRI consists of T2-weighted imaging (T2WI) combined with several functional sequences including diffusion-weighted imaging (DWI), perfusion or dynamic contrast enhanced imaging (DCEI) and spectroscopic imaging. Recently, mp-MRI has been used to assess prostate cancer aggressiveness and to identify anteriorly located tumors before and during active surveillance. Moreover, recent studies have reported that mp-MRI is a reliable imaging modality for detecting local recurrence after radical prostatectomy or external beam radiation therapy. Because assessment on mp-MRI can be subjective, use of the newly developed standardized reporting Prostate Imaging and Reporting Archiving Data System (PI RADS) scoring system and education of specialist radiologists are essential for accurate interpretation. This review focuses on the current place of mp-MRI in prostate cancer and its evolving role in the management of prostate cancer. PMID- 26682146 TI - Humongous right atrial lipoma: a correlative CT and MR case report. AB - A 66-year-old man was referred to our department for further investigation of a right atrial mass incidentally discovered on ultrasound examination (US). US showed an oval mass arising from the free wall of the right atrium and projecting into the atrial cavity. The mass was hypoechoic and had a broad base of attachment on the free wall of the right atrium. This case was referred to our department in order to perform an MR cardiac examination. Our diagnosis was supported by a CT scan study that confirmed the diagnosis of a cardiac lipoma subsequently confirmed at surgery. PMID- 26682147 TI - A rare case report of myxoid fibroma of maxilla. AB - This case report describes about a swelling in maxillary right posterior teeth region. On examination the swelling was solid, pinkish, red, non-ulcerated & non tender overgrowth at the right maxillary posterior teeth region with no buccal or palatal expansion. Panoramic radiograph revealed a faint radiolucent area with few radiopaque foci and histopathological examination showed myxoid fibroma. Further, correlation of clinical, radiological & histopathological feature; essential to diagnose lesion which lack the characteristic features are also discussed. PMID- 26682148 TI - A stubborn anemia caused by ectopic pancreas bleeding in the jejunum revealed by capsule endoscopy. AB - Ectopic pancreas is extremely rare in clinical setting. Meanwhile, a stubborn anemia without obvious dark bloody stool due to ectopic pancreas diagnosed by capsule endoscopy has not been reported. We reported a case of an ectopic pancreas inducing obscure gastrointestinal bleeding in a 70-year-old woman presenting as stubborn anemia, which was diagnosed by capsule endoscopy. The patient recovered well after resection the lesion. Diagnosis of ectopic pancreas is extremely difficult with conventional techniques. Endoscopists should pay more attention to the ectopic pancreas as a rare differential consideration for occult intestinal bleeding. PMID- 26682150 TI - On difference between fundamental science search and applicational technology research: a perspective from a Chinese doctor. PMID- 26682149 TI - Incidental finding of elongated ventral duct in a case of pancreatic divisum mimicking double pancreatic ducts on magnetic resonance cholangiopancreaticography-a rare normal variant. AB - Anatomic variations and developmental anomalies of the pancreas and pancreatic duct are often noticed as an incidental finding on imaging. However, knowledge of these variants may prove to be crucial during surgery as it may prevent unintentional ductal injury. We report a case of pancreatic divisum with codominant ventral duct mimicking double pancreatic ducts along with the elongated uncinate process of pancreas. It was picked incidentally on magnetic resonance cholangiopancreaticography (MRCP) done to rule out cholelithiasis and choledocholithiasis. It is a rare anatomic variant and to the best of our knowledge has not been reported so far. PMID- 26682151 TI - The role of Chaoyang People's Hospital for the development of trioxide as an effective treatment for acute promyelocytic leukemia treatment. PMID- 26682152 TI - Anti-apoptosis effects of vascular endothelial cadherin in experimental corneal neovascularization. AB - AIM: To explore the effects and mechanism of vascular endothelial cadherin (VE cadherin) on experimental corneal neovascularization (CRNV). METHODS: Mouse corneas were burned with sodium hydroxide to build a CRNV model. The burned corneas were locally administrated with anti-mouse VE-cadherin neutralizing antibody. Annexin V and cluster of differentiation 31 (CD31) double staining was used to measure vascular endothelial cell apoptosis with the use of flow cytometry (FCM). The protein expression of NADPH oxidase 2 (Nox2), caspase-3, and protein kinase C (PKC) in the burned corneas were examined by Western blot. Human retinal endothelial cell (HREC) proliferation was detected using a Cell Counting Kit 8 (CCK-8) assay in vitro. RESULTS: The amount of CRNV peaked two weeks after the alkali burn. FCM confirmed that VE-cadherin neutralizing antibody treatment increased CD31 positive cell apoptosis. Western blot revealed that the intracorneal protein expression of Nox2 and caspase-3 were up-regulated, while PKC was down-regulated in the VE-cadherin neutralizing antibody administrated group. CCK-8 assay showed that VE-cadherin neutralizing antibody markedly inhibited HREC proliferation. CONCLUSION: VE-cadherin exhibited an anti-apoptosis effect through enhanced PKC signaling and an enhanced cell proliferation pathway. PMID- 26682153 TI - Influence of transient intraocular pressure elevation during laser in situ keratomileusis on rabbit retina thickness. AB - AIM: To utilize tissue micro measurement to study the effect of transient high intraocular pressure (IOP) induced by different durations of suction during laser in situ keratomileusis (LASIK) on rabbit retina thickness. METHODS: Sixty healthy New Zealand white rabbits were randomly divided into a control group, and 3 negative-pressure suction groups (20s group, 45s group, and 3min group) and each group was comprised of 15 rabbits (30 eyes); the latter 3 groups were the transient high IOP models. The retinal tissue around the papilledema was separated. Hematoxylin and eosin (HE) staining was carried out to generate slices for light microscopy. The changes in the retina thickness values of each layer were measured for all animals in each group at different postoperative recovery periods and compared with the values recorded for the animals in the control group. The thickness of the retinal tissue showed a normal distribution. The ANOVA was performed by using SPSS13.0 statistic software. RESULTS: In the comparison between the 20s and 45s negative-pressure suction groups and the control group, no significant differences were observed, except at 14d. Significant difference was observed between the 3min negative-pressure suction group and the control group, and the retina thickness value of each layer reached a peak at 14d after repair. CONCLUSION: Conventional negative suction during LASIK may not lead to significant changes in retinal tissue thickness; however, if the suction duration is increased to 3min, it will cause significant changes in retinal tissue thickness. PMID- 26682154 TI - Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats. AB - AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism. PMID- 26682155 TI - Extraction (DSX) from Erigeron breviscapus modulates outward potassium currents in rat retinal ganglion cells. AB - AIM: To investigate the effect of DSX, an active component extracted from Erigeron breviscapus, on the voltage-gated outward K(+) channel currents in rat retinal ganglion cells (RGCs) by using electrophysiological method, and to explore the possible mechanisms of DSX on optic nerve protection. METHODS: Outward K(+) currents were recorded by using whole-cell patch-clamp techniques on acutely isolated rat RGCs. Outward K(+) currents were induced by a series of depolarizing voltage pulses from a holding potential of -70 mV to +20 mV in an increment of 10 mV. RESULTS: Extracellular application of DSX voltage-dependently suppressed both the steady-state and peak current amplitudes of outward K(+) currents in rat RGCs. Furthermore, DSX reversibly and dose-dependently inhibited the amplitudes of outward K(+) currents of the cells. At +20 mV membrane potential DSX at the concentrations of 0.02 g/L and 0.05 g/L showed no significant effects on the currents. In contrast, DSX at higher concentrations (0.1 g/L, 0.2 g/L and 0.5 g/L) significantly suppressed the current amplitudes. CONCLUSION: These results suggest that DSX reversibly and dose-dependently suppress outward K(+) channel currents in rat RGCs, which may be one of the possible mechanisms underlying Erigeron breviscapus prevents vision loss and RGC damage caused by glaucoma. PMID- 26682156 TI - Frequency spectrum might act as communication code between retina and visual cortex I. AB - AIM: To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I (V1). METHODS: Fourteen C57BL/6J mice were measured with pattern electroretinogram (PERG) and pattern visually evoked potential (PVEP) and fast Fourier transform has been used to analyze the frequency components of those signals. RESULTS: The amplitude of PERG and PVEP was measured at about 36.7 uV and 112.5 uV respectively and the dominant frequency of PERG and PVEP, however, stay unchanged and both signals do not have second, or otherwise, harmonic generation. CONCLUSION: The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex. The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1. PMID- 26682157 TI - A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree. AB - AIM: To identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD). METHODS: A southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members. RESULTS: The results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation. CONCLUSION: All modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD. PMID- 26682158 TI - Pterygium epithelium abnormal differentiation related to activation of extracellular signal-regulated kinase signaling pathway in vitro. AB - AIM: To investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro. METHODS: The expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis. RESULTS: The expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression. CONCLUSION: We suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation. PMID- 26682159 TI - Correlation between polymorphisms in the MFN1 gene and myopia in Chinese population. AB - AIM: To explore whether genetic variations in the MFN1 gene are associated with low to moderate myopia in Chinese population. METHODS: The case-control association analysis was used. The study included 100 independent myopia patients (-0.75 D <= spherical refraction <=-8.00 D) and 100 sex-matched healthy controls (with binocular spherical equivalent ranges between -0.50 D and +0.50 D). Four single nucleotide polymorphism (SNP) tags (rs3976523, rs13098637, rs6762399 and rs7618348) were selected for genotyping by direct sequencing. The frequencies of genotypes and their alleles were calculated based on the number of SNP genotypes in each sample. The Chi-square test was used to examine the difference in the frequency between the myopia cases and controls. RESULTS: Genotype distributions in the four SNPs were all in accordance with the Hardy-Weinberg equilibrium; analysis showed that rs13098637 was significantly associated with low to moderate myopia (P=0.003 and empirical P=0.010). There were no statistically significant differences observed for the genotype or allele frequencies of the other three SNPs between the myopia cases and controls in the Chinese population in this study. CONCLUSION: The current study has revealed that the C allele of rs13098637 in MFN1 had a significant association with low to moderate myopia. PMID- 26682160 TI - Comparation of effectiveness of silicone hydrogel contact lens and hydrogel contact lens in patients after LASEK. AB - AIM: To conduct a comparative study of effectiveness of silicone hydrogel contact lens and hydrogel contact lens, which are used in patients after laser-assisted subepithelial keratomileusis (LASEK). METHODS: Sixty-three patients (121 eyes) with a spherical equivalent <=-5.0 D were chosen after undergoing LASEK in 2012 at Guangdong General Hospital. They were randomly divided into 2 groups. The silicone hydrogel group included 32 cases (61 eyes) that wore silicone hydrogel contact lenses for 4-6d after the operation, while the hydrogel group included 31 cases (60 eyes) who wore hydrogel contact lenses for 4-6d after the operation. Patients' self-reported postoperative symptoms (including pain, photophobia, tears, and foreign body sensation) were evaluated. The healing time of the corneal epithelium, the visual acuity of patients without contact lens after epithelial healing, and the incidence of delayed corneal epithelial shedding were also assessed. The follow-up time was 1mo. RESULTS: Postoperative symptoms were milder in the silicone hydrogel group than in the hydrogel group. There were significant differences in pain, foreign body sensation, and photophobia between the 2 groups (P<0.05), although there was no significant difference in postoperative tearing (P>0.05). The healing time of the corneal epithelium in the silicone hydrogel lens group was markedly shorter than that in the hydrogel group (4.07+/-0.25 vs 4.33+/-0.82d, t=2.43, P=0.02). Visual acuity without contact lenses after healing of the corneal epithelium was better in the silicone hydrogel group compared with the hydrogel group (chi (2)=7.76, P=0.02). There was no significant difference in the occurrence of delayed corneal epithelial shedding between the 2 groups (P>0.05). CONCLUSION: Patients with LASEK using silicon hydrogel contact lenses had less discomfort and shorter corneal epithelial healing time compared with those using hydrogel contact lenses, suggesting that silicon hydrogel contact lenses may be considered to be a better choice of bandage contact lens after LASEK. PMID- 26682161 TI - Correlation of basic indicators with stages of keratoconus assessed by Pentacam tomography. AB - AIM: To evaluate the diagnostic efficiency of basic indicators and find characteristic indicators for keratoconus (KC) at adjacent stages, and to assess the progression pattern of KC. METHODS: One hundred and eight (41 subclinical, 40 moderate, and 27 severe) keratoconic patients (108 eyes) and 105 myopic patients (105 eyes) as controls were recruited in this prospective, comparative case series study. Pentacam topography was performed. Receiver-operating characteristic curves were used to get the characteristic indicators. RESULTS: The most efficient distinguishing index between the subclinical KC and the controls was posterior elevation value (PEV, AUC=0.882), with the highest specificity being 93.8%. Corneal thickness (AUC=0.852) and posterior inferior superior value (I-S) ranked second and third (AUC=0.776). When KC became moderate, PEV remained to be of the highest diagnostic efficiency (AUC=0.988), followed by the anterior elevation value (AUC=0.986) and other parameters of anterior surface. The diagnostic value increased significantly in the anterior curvature indices (all AUC>0.900) and appeared in the anterior best fitting sphere radius (AUC=0.919) when KC developed into the severe stage. CONCLUSION: In the subclinical stage of KC, PEV, thickness, and posterior I-S had important diagnostic values, and elevation values remained most efficient when KC developed to the moderate stage. The anterior curvature indices were most characteristic when KC became severe. KC first appeared in the inferior cornea of posterior surface, but the feature of protrusion formed at the moderate stage. PMID- 26682162 TI - In-vivo corneal biomechanical analysis of unilateral keratoconus. AB - AIM: To evaluate and compare corneal biomechanical findings measured by ocular response analyzer, topographic and pachymetric findings in patients with unilateral keratoconus patients and healthy controls. METHODS: This is an observational, case-control study. Patients with keratoconus in one eye and forme fruste keratoconus in the fellow eye were compared with sex and age matched with controls healthy subjects. All subjects were evaluated with rotating scheimpflug imaging system. The receiver-operating-characteristic curves were analyzed to evaluate the sensitivity and specificity of the parameters. RESULTS: Twenty-seven patients with keratoconus in one eye and forme fruste keratoconus in the fellow eye were compared with 40 eyes of 40 normal subjects. Corneal hysteresis (CH) was 8.0+/-1.7 mm Hg in keratoconus group, 8.3+/-1.6 mm Hg in forme fruste keratoconus group, and 9.8+/-1.6 mm Hg in control groups (P=0.54 between keratoconus and forme fruste keratoconus groups, P<0.01 between control group and other groups). Corneal resistance factor (CRF) was 7.1+/-2.2 mm Hg in keratoconus group, 7.8+/ 1.2 mm Hg in forme fruste keratoconus group and 9.9+/-1.5 mm Hg in control group (P<0.001 between control group and other groups). Using receiver-operating characteristic analysis, the area under curve values of the parameters to distinguish forme fruste keratoconus from control subjects were: CH (0.768), CRF (0.866). Best cut-off points were 9.3 mm Hg and 8.8 mm Hg for CH and CRF respectively. CONCLUSION: Ocular response analyzer parameters (CH and CRF) are found to be significantly lower in forme fruste keratoconus patients compared to normal control subjects. PMID- 26682163 TI - Comparison of pseudophakic retinal straylight in spherical/aspherical and hydrophobic/hydrophilic intraocular lens. AB - AIM: To study the potential reasons of increased straylight in pseudophakic eyes. METHODS: Cross-sectional study. Seventy patients diagnosed as bilateral age related cataract and implanted with Tecnis ZA9003, Sensar AR40e, SA60AT, XLSTABI ZO or Akeros AO intraocular lens (IOL) were enrolled in this research. Straylight was measured by a C-Quant straylight meter three to four weeks postoperatively. Five different modalities of IOL, including spherical/aspherical optics and hydrophobic/hydrophilic material were tested in this study. Normal as well as dilated pupils were used. The main outcome variable for straylight measurement was the logarithmic straylight parameter, log(s). RESULTS: The straylight parameter increased significantly after pupil dilation (P<0.05). Straylight of aspherical IOL was significantly higher after pupil dilation (P<0.05) compared to spherical IOL. In normal pupil, straylight of hydrophobic IOL was significant higher when compared with hydrophilic IOL (P<0.05). CONCLUSION: Straylight and visual acuity stand for the different aspects of visual function. Several factors including pupil diameter, optic material, aspherical design of IOL influence intraocular light scattering in pseudophakic eyes. Further investigation was needed to study the impact of optic material and optic surface design on pseudophakic straylight. PMID- 26682164 TI - Lens thickness assessment: anterior segment optical coherence tomography versus A scan ultrasonography. AB - AIM: To assess lens thickness measurements with anterior segment-optical coherence tomography (AS-OCT) in comparison with A-scan ultrasonography (A-scan US). METHODS: There were 218 adult subjects (218 eyes) aged 59.2+/-9.2y enrolled in this prospective cross-sectional study. Forty-three eyes had open angles and 175 eyes had narrow angles. Routine ophthalmic exam was performed and nuclear opacity was graded using the Lens Opacities Classification System III (LOCS III). Lens thickness was measured by AS-OCT (Visante OCT, Carl Zeiss Meditec, Dublin, CA, USA). The highest quality image was selected for each eye and lens thickness was calculated using ImageJ software. Lens thickness was also measured by A-scan US. RESULTS: Interclass correlations showed a value of 99.7% for intra-visit measurements and 95.3% for inter-visit measurements. The mean lens thickness measured by AS-OCT was not significantly different from that of A-scan US (4.861+/-0.404 vs 4.866+/-0.351 mm, P=0.74). Lens thickness values obtained from the two instruments were highly correlated overall (Pearson correlation coefficient=0.81, P<0.001), and in all LOCS III specific subgroups except in grade 5 of nuclear opacity. Bland-Altman analysis revealed a 95% limit of agreement from -0.45 to 0.46 mm. Lens thickness difference between the two instruments became smaller as the lens thickness increased and AS-OCT yielded smaller values than A-scan US in thicker lens (beta=-0.29, P<0.001). CONCLUSION: AS-OCT-derived lens thickness measurement is valid and comparable to the results obtained by A-scan US. It can be used as a reliable noncontact method for measuring lens thickness in adults with or without significant cataract. PMID- 26682165 TI - Correlations between corneal and optic nerve head variables in healthy subjects and patients with primary open angle glaucoma. AB - AIM: To correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG). METHODS: Measurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the HRT. RESULTS: The following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P<0.0001), Zone I-DAr (-0.503; P<0.0001) and Zone II-DAr (-0.443; P<0.0001); and in the POAG group: CCT-cup-to-disc area ratio (CDRa) (-0.402; P<0.0001), Zone I-CDRa (-0.418; P<0.0001), Zone II-CDRa (-0.405; P=0.006), Zone I cup shape measure (CSM) (-0.415; P=0.002), Zone II-CSM (-0.405; P=0.001), Zone IV height variation contour (HVC) (0.378; P=0.002); Zone V-HVC (0.388, P<0.0001). CONCLUSIONS: In the healthy subjects, significant negative correlation was detected between central and paracentral corneal thickness and optic disc area. In contrast, the POAG patients showed significant negative correlation between central and paracentral corneal thickness and the cup-disc ratio and CSM, and positive correlation between peripheral corneal thickness and HVC. PMID- 26682167 TI - Comparison of 45-degree Kelman and 45-degree balanced phaco tip designs in torsional microcoaxial phacoemulsification. AB - AIM: To compare the intraoperative performance and postoperative outcome after microcoaxial torsional phacoemulsification using either a Kelman or balanced phaco tip. METHODS: Cataracts were treated using 2.2 mm microcoaxial torsional phacoemulsification using either a 45-degree mini-flared Kelman((r)) or a 45 degree Intrepid((r)) Balanced phaco tip. Intraoperative measurements included total ultrasound (US) time, cumulative dissipated energy (CDE), torsional US time, and balanced salt solution (BSS) use. The central endothelial cell density (ECD) and central corneal thickness (CCT) were evaluated preoperatively and postoperatively 1, 7, and 30d after surgery using noncontact specular microscopy. RESULTS: The 116 enrolled eyes (116 patients) were divided equally between the Kelman and balanced tip groups. Intraoperative measurements showed significantly less total US time, torsional US time, CDE, and BSS use in the balanced group than in Kelman group (P<0.05). The total US time, torsional US time, CDE, and BSS use were 17.45+/-14.53s, 16.63+/-13.97s, 6.38+/-5.26, and 48.21+/-17.21 mL in the Kelman group and 11.39 +/- 9.60s, 10.90 +/- 9.25s, 4.04 +/- 3.42, and 41.36 +/- 12.70 mL in the balanced group, respectively. CONCLUSION: Torsional phacoemulsification performed with a balanced tip provided more effective lens removal with less total US time, torsional time, CDE, and BSS use, as well as similar changes in ECD with a Kelman tip in all cataract grades. This special designed phaco tip for torsional phacoemulsification provides an alternative phaco tip for many surgeons' preference with straight phaco tip. PMID- 26682166 TI - Long-term results of viscocanalostomy and phacoviscocanalostomy: a twelve-year follow-up study. AB - AIM: To evaluate the long-term efficacy and safety results of viscocanalostomy and phacoviscocanalostomy. METHODS: The charts of 49 glaucoma patients who underwent viscocanalostomy or phacoviscocanalostomy surgery between February 1999 and August 2004 were reviewed retrospectively. Thirty-one eyes of 21 glaucoma patients who underwent filtering procedure with a postoperative follow-up of at least 5y were included in the study. Results of complete ophthalmologic examinations were recorded and statistically analyzed. Long-term surgical outcome was defined as an overall success when intraocular pressure (IOP) was found as <=20 mm Hg with or without antiglaucomatous medication at the last follow-up visit, while it was defined as a complete success when IOP was measured <=20 mm Hg without antiglaucomatous medication. RESULTS: Mean age was 68.1+/-9.6y (range: 32-81y). Mean follow-up time was 101.5+/-27.3mo (range: 60-144mo). Viscocanalostomy was performed in 8 eyes (25.8%) and phacoviscocanalostomy was performed in 23 eyes (74.2%). The mean preoperative IOP was 23.1+/-7.6 mm Hg with 2.1+/-1.0 medications, while mean IOP was 16.8+/-3.8 mm Hg with 0.9+/-1.1 medication at the last follow-up visit. Both the IOP decrease and the reduction in the antiglaucomatous medication were statistically significant (P<0.001 and P<0.001). No case required further glaucoma surgery. Overall success and complete success were found as 87.1% and 51.6%, respectively. Complete success rate was statistically higher in phacoviscocanalostomy group compared with the viscocanalostomy group (P=0.031), however there was no significant difference in overall success rate between two groups (P=0.072). CONCLUSION: Both viscocanalostomy and phacoviscocanalostomy provide good IOP reduction in the long term period. PMID- 26682168 TI - A comparison of visual outcomes in three different types of monofocal intraocular lenses. AB - AIM: To compare the visual outcomes (distance and near) in patients opting for three different types of monofocal intraocular lens (IOL) (Matrix Aurium, AcrySof single piece, and AcrySof IQ lens). METHODS: The present study is a cross sectional analysis of secondary clinical data collected from 153 eyes (52 eyes in Matrix Aurium, 48 in AcrySof single piece, and 53 in AcrySof IQ group) undergoing cataract surgery (2011-2012). We compared near vision, distance vision, distance corrected near vision in these three types of lenses on day 15 (+/-3) post surgery. RESULTS: About 69% of the eyes in the Matrix Aurium group had good uncorrected distance vision post-surgery; the proportion was 48% and 57% in the AcrySof single piece and AcrySof IQ group (P=0.09). The proportion of eyes with good distance corrected near vision were 38%, 33%, and 15% in the Matrix Aurium, AcrySof single piece, and AcrySof IQ groups respectively (P=0.02). Similarly, The proportion with good "both near and distance vision" were 38%, 33%, and 15% in the Matrix Aurium, AcrySof single piece, and AcrySof IQ groups respectively (P=0.02). It was only the Matrix Aurium group which had significantly better both "distance and near vision" compared with the AcrySof IQ group (odds ratio: 5.87, 95% confidence intervals: 1.68 to 20.56). CONCLUSION: Matrix Aurium monofocal lenses may be a good option for those patients who desire to have a good near as well as distance vision post-surgery. PMID- 26682169 TI - Comparison of 25-gauge sutureless vitrectomy and 20-gauge vitrectomy in the treatment of posterior capsule opacification in pseudophakic children. AB - AIM: To compare the effectiveness and safety of pars plana capsulotomy and vitrectomy using 25-gauge tansconjunctival sutureless vitrectomy system and 20 gauge vitrectomy system for posterior capsule opacification (PCO) in pseudophakic children. METHODS: Retrospectively study. Pars plana capsulotomy and vitrectomy using 25-gauge sutureless vitrectomy system was performed for PCO in the study group (32 eyes). Patients in the control group (34 eyes) underwent capsulotomy and vitrectomy using standard 20-gauge vitrectomy system, providing a comparison between 2 groups with regard to preoperative and postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), and intraoperative and postoperative complications. The two groups were performed consequentially. The patients ages ranged from 2 to 13y (means: 6.61+/-2.73y). Surgical technique, intraoperative and postoperative complications, visual acuity, IOP, and recurrent PCO were recorded. RESULTS: The surgical procedure was performed uneventfully in all patients. Visual acuity improved significantly in both groups. BCVA improved in 22 eyes (81.5%) in the study group and in 28 eyes (87.5%) in the control group. There was no statistical difference of visual acuity that were attainable in two groups (H=0.115, P=0.909). Mean postoperative IOP showed no significant difference between the groups at 1wk. All sort of PCO were accomplished by 20 gauge system, while 25-gauge system was effective for pearls style and 2 grade of fibrous PCO, and was insufficient to grade 3 of PCO. In the study group two cases were not accomplished by 25-gauge system while 20-gauge system conquered them. Compared with the control group, mean operative time for opening and closing the sclerotomy in the study group was considerably reduced. The mean follow-up was 38.2mo (range: 8-79mo). During the follow-up period, no incision leakage, corneal edema, vitreous loss, IOL damage, retinal detachment, recurrent PCO, or other complications were noted. CONCLUSION: Pars plana capsulotomy and vitrectomy using 25-gauge transconjunctival sutureless vitrectomy appeared to be a safe and effective approach for PCO in pseudophakic children. Combined sutureless surgery needed shorter setup time for sclerotomy and caused less surgical trauma than combined surgery with 20-gauge vitrectomy. Therefore, this type of procedure would be a good option for selected cases with PCO in pseudophakic children. PMID- 26682170 TI - Risk factors for endophthalmitis following cataract surgery-our experience at a tertiary eye care centre in India. AB - AIM: To determine the risk factors for acute endophthalmitis after cataract extraction in a tertiary care centre in India. METHODS: We performed a nested case control study within a retrospective cohort. The surgical records of all patients with clinically diagnosed endophthalmitis within one month after cataract surgery, performed between January 2006 and December 2009, were reviewed. These were compared with randomly selected age and gender-matched controls, from patients having routine cataract surgery within +/-1wk of the endophthalmitis case. Univariable and multivariable analysis were performed to identify risk factors for endophthalmitis. RESULTS: Of the total 33 856 cataract surgeries performed during this period, there were 57 cases of postoperative acute endophthalmitis that met our study criteria. Thus, the overall incidence of endophthalmitis in our cohort was 1.6 per 1000 cataract extractions performed. Mean age of cases was 55.9y (SD: 10.9y) and for controls was 55.6y (SD: 9.8y). Thirty-five cases (61.4%) and 133 controls (59.6%) were males. Median time of onset of endophthalmitis was 4d (IQR 2-9d; range: 1-30d). Thirty-nine cases (68.4%) presented within 7d and 27 cases (47.4%) were culture positive. Two hundred and twenty-three age and gender matched controls were selected. In multivariate analysis, endophthalmitis was associated with posterior capsular rupture (PCR) during surgery (OR 6.98, 95%CI: 2.22-21.98), phacoemulsification via scleral incision with a foldable intraocular lens (IOL) implantation (OR 3.02, 95%CI: 1.13-8.04) and ocular co-morbidity (OR 2.32, 95%CI: 1.11-4.87). CONCLUSION: PCR, presence of ocular co-morbidity, and phacoemulsification via scleral incision with foldable-IOL were found to be independent risk factors for acute endophthalmitis. PMID- 26682171 TI - Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration. AB - AIM: To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS: Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS: MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48+/-0.18. Patients with early AMD (0.52+/-0.19) tended to have higher MPOD levels than healthy people (0.47+/ 0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION: Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels. PMID- 26682172 TI - Comparison and interchangeability of macular thickness measured with Cirrus OCT and Stratus OCT in myopic eyes. AB - AIM: To investigate the difference of macular thickness measurements between stratus optical coherence tomography (OCT) and Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA) in the same myopic patient and to develop a conversion equation to interchange macular thickness obtained with these two OCT devices. METHODS: Eighty-nine healthy Chinese adults with spherical equivalent (SE) ranging from 1.13 D to -9.63 D were recruited. The macular thickness was measured by Cirrus OCT and Stratus OCT. The correlation between macular thickness and axial length and the agreement between two OCT measurements were evaluated. A formula was generated to interchange macular thickness obtained with two OCT devices. RESULTS: Average macular thickness measured with Stratus OCT (r=-0.280, P=0.008) and Cirrus OCT (r=-0.224, P=0.034) were found to be negatively correlated with axial length. No statistically significant correlation was found between axial length and central subfield macular thickness (CMT) measured with Stratus OCT (r=0.191, P=0.073) and Cirrus OCT (r=0.169, P=0.113). The mean CMT measured with Cirrus OCT was 53.63+/-7.94 um thicker than with Stratus OCT. The formula CMTCirrus OCT=78.328+0.874*CMTStratus OCT was generated to interchange macular thickness obtained with two OCT devices. CONCLUSION: Macular thickness measured with Cirrus OCT were thicker than with Stratus OCT in myopic eyes. A formula can be used to interchange macular thickness measured with two OCT devices in myopic eyes. Studies with different OCT devices and larger samples are warranted to enable the comparison of macular values measured with different OCT devices. PMID- 26682173 TI - Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab. AB - AIM: To evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR). METHODS: This study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively. RESULTS: In PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis. CONCLUSION: We found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF. PMID- 26682174 TI - Postnatal weight gain in very low birth weight infants in Beijing and the risk of retinopathy of prematurity. AB - AIM: To analyze the low weight gain (WG) from birth to 4 and 6wk of life to predict the development of retinopathy of prematurity (ROP) among very low birth weight (VLBW) preterm babies. METHODS: Three hundred and three newborns with VLBW were analyzed. Body weight measurements were recorded weekly. In all patients, the proportion of the WG was defined as the preterm weight measured at the 4(th) and 6(th) weeks of life minus the birth weight (BW) divided by the BW. Other risk factors for ROP were also analyzed. RESULTS: Mean gestational age and mean BW of the whole cohort were 29.56+/-1.44wk and 1270.58+/-176.18g respectively. WG proportion at 4wk postnatal age (18.89%+/-13.58%) were significantly lower in infants with ROP (P=0.003). WG proportion at 6wk was not different between ROP and no ROP group (42.48%+/-20.36% vs 46.43%+/-15.65% P=0.118). When all the other risk factors significant for ROP were included in the logistic regression poor WG did not arise as an independent risk factor. Area under the ROC curve was 0.591 (95%CI: 0.515-0.666; P=0.016). For ROP, the best discriminative cutoff of 18.06% of the proportional WG at the 4(th) week over the BW, sensitivity and specificity values were 67.3% and 50.0% respectively. CONCLUSION: Low WG proportion in the first 4wk of life is maybe an additional predictor of ROP in very low BW infants. Preterm babies with low BW and low WG proportion should be followed closely for ROP. PMID- 26682175 TI - A study of retinal parameters measured by optical coherence tomography in patients with multiple sclerosis. AB - AIM: To investigate the difference of retinal nerve fiber layer (RNFL) thickness and macular fovea thickness/volume between multiple sclerosis (MS) patients and healthy normal individuals using optical coherence tomography (OCT) and assess its association with visual field parameters. METHODS: Thirty consecutive MS patients and 28 healthy controls were recruited in this prospective study. Comprehensive standardized ophthalmic examinations included visual acuity, cycloplegic refraction, intraocular pressure, gonioscopy, visual field, and RNFL thickness and macular fovea thickness/volume detection using Humphrey OCT. Mean values for the thickness of the peripapillary RNFL and macular volume were calculated. Associations between visual field parameters and RNFL thickness/macular volume were analyzed by Pearson correlation analysis. RESULTS: The RNFL thicknesses in each quadrant, the average macular thickness, and the average macular volume in MS patients were all less than those in healthy controls, with statistically significant differences. The RNFL thickness and macular fovea thickness/volume were greater in eyes without optic neuritis than in eyes with optic neuritis. The average visual field parameters had positive correlations with the RNFL thickness and negative correlations with macular parameters in MS patients. CONCLUSION: OCT measurements can effectively identify the nerve changes of MS patients, which provide more data for the diagnosis of MS. PMID- 26682176 TI - Clinical features and visual outcomes of scleritis patients presented to tertiary care eye centers in Saudi Arabia. AB - AIM: To describe the clinical features, systemic associations, treatment and visual outcomes in Saudi patients with scleritis. METHODS: A retrospective chart review was performed for patients with scleritis presenting to two tertiary care eye hospitals in Riyadh, Saudi Arabia, from 2001 to 2011. Data were collected on the clinical features of scleritis, subtypes of scleritis, associated systemic disease, history of previous ocular surgery and medical therapy, including the use of immunosuppressants. Treatment outcomes were evaluated based on best corrected visual acuity (BCVA) and response to treatment. RESULTS: Of the 52 patients included in the study, non-necrotizing anterior scleritis was the most common type of scleritis in 22 patients (42.3%), followed by posterior scleritis in 14 patients (26.9%). The majority of cases, 31 patients (59.6%), were idiopathic in nature. Systemic associations were present in 12 patients (23.1%). Infectious scleritis was confirmed in 6 patients (11.5%): 3 with bacterial scleritis after pterygium excision, 2 patients with scleritis related to tuberculosis and 1 patient with scleritis resulting from herpes simplex infection. For the various subtypes of scleritis, BCVA values after treatment and time to remission significantly differed (P<0.05, all cases). Systemic immunosuppressive therapies in addition to steroids were administered to 46.2% of all patients. The T-sign was present on B-scan ultrasonography in 9 (64.3%) of the 14 posterior scleritis patients. CONCLUSION: Non-necrotizing anterior scleritis was the most common subtype of scleritis. Final visual outcome and time to remission differed among the various scleritis subtypes. PMID- 26682177 TI - Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives. AB - AIM: To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. METHODS: In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm(2)/d) compared in each group using Kruskal-Wallis tests. RESULTS: There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93+/-2.69d (levofloxacin group), 10.31+/-2.96d (gatifloxacin group), and 13.50+/-4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18+/-1.39 mm(2)/d (levofloxacin group), 5.52+/ 1.68 mm(2)/d (gatifloxacin group), and 4.40+/-1.30 mm(2)/d (moxifloxacin group), P=0. 003. CONCLUSION: Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin. PMID- 26682178 TI - Factors influencing improvement of visual field after trans-sphenoidal resection of pituitary macroadenomas: a retrospective cohort study. AB - AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans sphenoidal surgery. Ophthalmologic evaluation, best-corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23+/ 1.29y. Ninety-three patients were female and 108 were male. The mean tumor volume was 14.36+/-6.23 cm(3). The mean duration of preoperative symptoms was 11.50+/ 0.88mo. Mean preoperative MD was -17.50+/-0.82 dB. Mean Preoperative visual acuity was 0.64+/-0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/ Ki-67. PMID- 26682179 TI - Visual outcomes in patients with open globe injuries compared to predicted outcomes using the Ocular Trauma Scoring system. AB - AIM: To determine the visual outcomes in adult patients who sustained open globe injuries and to determine whether the visual prognosis following an eye injury in an African setting differs from the predicted outcomes according to the Ocular Trauma Score (OTS) study. A secondary aim was to establish the evisceration rate for these injuries and assess how this form of intervention affected outcomes in comparison to the OTS. METHODS: A prospective case series of all patients admitted with open globe injuries over a two-year (July 2009 to June 2011) period. Injuries were scored using the OTS and the surgical intervention was recorded. The best corrected visual acuity at three months was regarded as visual outcome. RESULTS: There were 249 open globe injuries, of which 169 patients (169 eyes) completed the 3-month follow-up. All patients underwent primary surgery, 175 (70.3%) repairs, 61 (24.5%) eviscerations and 13 (5.2%) other procedures. Globe eviscerations were mainly done on OTS Category 1 cases, but outcomes in this category were not found to be different from OTS outcomes. Outcomes were significantly worse in Category 2, but when the entire distribution was tested, the differences were not statistically significant. The overall association between OTS outcomes and the final visual outcomes in this study was found to be a strong (P<0.005). CONCLUSION: Reliable information regarding the expected outcomes of eye injuries will influence management decisions and patient expectations. The OTS is a valuable tool, the use of which has been validated in many parts of the world-it may also be a valid predictor in an African setting. PMID- 26682180 TI - Comparison of intravitreal bevacizumab with intravitreal triamcinolone acetonide for treatment of cystoid macular edema secondary to retinal vein occlusion: a Meta-analysis. AB - AIM: To compare the effects of intravitreal injection of bevacizumab (IVB) with intravitreal triamcinolone acetonide (IVTA) on the treatment of cystoid macular edema (CME) secondary to retinal vein occlusion (RVO). METHODS: A literature search was conducted using PubMed, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. The comparison was divided into two groups, group 1 conducted comparison in branch RVO (BRVO) or central RVO (CRVO), group 2 conducted comparison in ischemic-RVO or nonischemic RVO. Pooled mean differences (MDs) for changes in visual acuity (VA), central macular thickness (CMT) and intraocular pressure (IOP) were calculated in groups at 4, 12 and 24wk after treatment respectively. RESULTS: Eight studies comparing the efficacy of IVB with IVTA were included in the Meta-analysis. In group 1, in BRVO, significant difference was shown on the comparison of CMT at 24wk (MD, 45.66; 95% CI, -76.03 to -15.28; P=0.003), IVB was effective on BRVO for at least 24wk; no significant differences were found in the comparison of VA at each time points (P>0.05 respectively). In CRVO, no significant differences were found in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). In group 2, in ischemic-RVO, significant differences were shown in the comparison of VA (MD, -0.28; 95% CI, -0.42 to -0.14; P<0.0001) and CMT (MD, 86.50; 95% CI, -151.18 to -22.43; P=0.008) at 24wk; In nonischemic-RVO, no significant differences were demonstrated in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). The occurrence of high IOP was much lower in IVB group. CONCLUSION: This Meta-analysis suggested that IVB was effective in decreasing CMT in BRVO for at least 24wk, IVB is more effective on improving VA and reducing CMT in ischemic-RVO. IVB is more promising on RVO than IVTA. PMID- 26682181 TI - Optic nerve sheath diameters in healthy adults measured by computer tomography. AB - AIM: To measure optic nerve sheath diameters (ONSD) in different locations by computer tomography (CT) and to recommend the best location for cases when ONSD is used for intracranial pressure monitoring. METHODS: In a prospective cohort study, CT data of 300 healthy adults were analyzed (600 eyes). In all cases, the CT investigation was performed at the Emergency Department because of the various conditions that proved not to be connected with ophthalmological or neurological pathology. The ONSD were measured at 3 mm and 8 mm distance from the globe, and 3 mm from the anterior opening of the optic canal. The correlation analysis was performed with gender, age, and ethnic background. RESULTS: The right/left ONSD are 4.94+/-1.51/5.17+/-1.34 mm at 3 mm, 4.35+/-0.76/4.45+/-0.62 mm at 8 mm from the globe, and 3.55+/-0.82/3.65+/-0.7 mm at 3 mm from the optic canal. No significant differences correlated with gender of the patients, their age, and ethnic background were found. CONCLUSION: In healthy persons, the ONSD varies from 5.17+/-1.34 mm to 3.55+/-0.82 mm in different locations within the intraorbital space. The most stable results with lesser standard deviation can be obtained if it is measured 8-10 mm from the globe. PMID- 26682183 TI - Phacoemulsification in a rare case of keratoconus with Fuch's endothelial corneal dystrophy. PMID- 26682182 TI - Recent advances in the dark adaptation investigations. AB - Dark adaptation is a highly sensitive neural function and may be the first symptom of many status including the physiologic and pathologic entity, suggesting that it could be instrumental for diagnose. However, shortcomings such as the lack of standardized parameters, the long duration of examination, and subjective randomness would substantially impede the use of dark adaptation in clinical work. In this review we summarize the recent research about the dark adaptation, including two visual cycles-canonical and cone-specific visual cycle, affecting factors and the methods for measuring dark adaptation. In the opinions of authors, intensive investigations are needed to be done for the widely use of this significant visual function in clinic. PMID- 26682184 TI - Assessment of glaucoma using extreme learning machine and fractal feature analysis. PMID- 26682185 TI - Visual outcomes of multifocal intraocular lens implantation in patients with cataract and high hyperopia and patient selection. PMID- 26682186 TI - Clinical manifestations and outcomes of ocular sarcoidosis in Saudi Arabia. PMID- 26682187 TI - An overview of viral and nonviral delivery systems for microRNA. PMID- 26682189 TI - Needle free injection technology: A complete insight. AB - Needle free injection technology (NFIT)is an extremely broad concept which include a wide range of drug delivery systems that drive drugs through the skin using any of the forces as Lorentz, Shock waves, pressure by gas or electrophoresis which propels the drug through the skin, virtually nullifying the use of hypodermic needle. This technology is not only touted to be beneficial for the pharma industry but developing world too find it highly useful in mass immunization programmes, bypassing the chances of needle stick injuries and avoiding other complications including those arising due to multiple use of single needle. The NFIT devices can be classified based on their working, type of load, mechanism of drug delivery and site of delivery. To administer a stable, safe and an effective dose through NFIT, the sterility, shelf life and viscosity of drug are the main components which should be taken care of. Technically superior needle-free injection systems are able to administer highly viscous drug products which cannot be administered by traditional needle and syringe systems, further adding to the usefulness of the technology. NFIT devices can be manufactured in a variety of ways; however the widely employed procedure to manufacture it is by injection molding technique. There are many variants of this technology which are being marketed, such as Bioject((r)) ZetaJetTM, Vitajet 3, Tev-Tropin((r)) and so on. Larger investment has been made in developing this technology with several devices already being available in the market post FDA clearance and a great market worldwide. PMID- 26682188 TI - Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs. AB - Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID- 26682190 TI - Eugenol significantly affects the flow of its nanodroplet gel. AB - INTRODUCTION: Development of novel biomaterials for drug delivery which forms a part of the so called novel drug delivery systems has always been exhilarating. Mechanical evaluation of polymer based topical gels, which would be subjected to load or stress during its application, is inevitable. METHODS: Rheological characterization was done by studying viscosity and yielding. Rheological modeling was also carried out. RESULTS: The viscosity and yield stress were inversely dependent on the eugenol concentration. The gels followed Herschel Bulkley and Bingham rheological models. CONCLUSION: Nanodroplets are colloidal systems and the microstructural changes in the Carbopol based nanodroplet gels were unveiled using rheometry. PMID- 26682191 TI - Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine. AB - BACKGROUND: The aim of the present study was to formulate and optimize the self emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 2(2) factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. MATERIALS AND METHODS: Solubility of NVP in different oils, surfactants, and co surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 2(2) factorial designs. RESULTS: The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. CONCLUSION: Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology. PMID- 26682192 TI - Investigation of hydrogel membranes containing combination of gentamicin and dexamethasone for ocular delivery. AB - BACKGROUND: Hydrogel is a cross-linked network of polymers. Water penetrates these network causing swelling and giving the hydrogel a soft and rubbery consistency and there by maintaining the integrity of the membrane. Due to the drawback of conventional therapy for ocular delivery, hydrogel membranes containing the combination of gentamicin (GT) sulfate and dexamethasone (DX) were formulated for the treatment of conjunctivitis. The objective of this study was to formulate and evaluate the hydrogel membranes containing the combination of GT and DX for the treatment of conjunctivitis. MATERIALS AND METHODS: In the present investigation, hydrogel membranes were prepared by using polymers such as gelatin, polyvinyl alcohol, and chitosan, which were cross-linked using physical/chemical methods. RESULTS: The cross-linking of the membranes was confirmed by Fourier transform infra-red studies. The pH of the membranes ranged from 7.19 to 7.45 and drug content ranged from 69.82% to 89.19%. The hydrogels showed a considerably good swelling ratio ranging from 22.5% to 365.56%. The in vitro drug release study showed that there was a slow and sustained release of the drug from the membranes which were sufficiently cross-linked and followed zero order release. In vivo studies showed that the severity of conjunctivitis was remarkably lowered at day 3 with hydrogel membrane compared to marketed eye drops. Results of unpaired t-test of significance between two groups indicated that the hydrogel membrane showed a better response in the treatment of conjunctivitis compared to the marketed products. Stability studies proved that the formulations could be stable when stored at room temperature. CONCLUSION: Results of the study indicated that it is possible to develop a safe and physiologically effective hydrogels which are patient compliant. PMID- 26682193 TI - Development and evaluation of in situ gel of pregabalin. AB - AIM AND BACKGROUND: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. MATERIALS AND METHODS: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 3(2) full factorial design. RESULTS: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm(2)). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. CONCLUSION: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy. PMID- 26682194 TI - Factorial designed 5-fluorouracil-loaded microsponges and calcium pectinate beads plugged in hydroxypropyl methylcellulose capsules for colorectal cancer. AB - INTRODUCTION: The work was aimed to develop an enteric-coated hydroxypropyl methylcellulose (HPMC) capsules (ECHC) plugged with 5-fluorouracil (5-FU)-loaded microsponges in combination with calcium pectinate beads. MATERIALS AND METHODS: The modified quasi-emulsion solvent diffusion method was used to prepare microsponges. A 3(2) factorial design was employed to study the formulation and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on dependent variables (particle size, %entrapment efficiency, and %cumulative drug release). The optimized microsponge (F4) was characterized by scanning electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. F4 was plugged along with the calcium pectinate beads in HPMC capsules coated with enteric polymer Eudragit-L100 (Ed-L100) and/or Eudragit-S100 (Ed S100) in different proportions. An in vitro release study of ECHC was performed in simulated gastric fluid for 2 h, followed by simulated intestinal fluid for next 6 h and then in simulated colonic fluid (in the presence and absence of pectinase enzyme for further 16 h). The optimized formulation was subjected to in vivo roentgenographic and pharmacokinetic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon-targeted capsules. RESULTS: Drug release was retarded on coating with Ed-S100 in comparison to a blend of Ed S100:Ed-L100 coating. The percentage of 5-FU released at the end of 24 h from ECHC3 was 97.83 +/- 0.12% in the presence of pectinase whereas in the control study, it was 40.08 +/- 0.02%. CONCLUSION: Thus, enteric-coated HPMC capsules plugged with 5-FU-loaded microsponges and calcium pectinate beads proved to be a promising dosage form for colon targeting. PMID- 26682195 TI - Dissolution enhancement of chlorzoxazone using cogrinding technique. AB - PURPOSE: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. MATERIALS AND METHODS: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. RESULTS: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40 degrees C/75% relative humidity). CONCLUSIONS: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability. PMID- 26682196 TI - Preparation and characterization of physicochemical properties of N, N-diethyl meta-toluamide niosomes. AB - INTRODUCTION: The insect repellent compounds are used to protect humans, animals and plants against insect bites. Aromatic amides have insect repellent effects. N,N-diethyl-meta-toluamide (DEET) (C12 H17 NO) is one of the best insect repellents has been used for many years. DEET is a colorless, odorless liquid that is approximately insoluble in water and soluble in glycerin, ethanol, and isopropyl alcohol. Due to the solubility problem of DEET, its topical formulations usually have alcoholic bases, but these kind of formulations increase skin permeation and also systemic absorption of DEET, which leads to some toxic effects. The main goal of this study was to prepare the formulation of DEET niosomes in a topical dosage form with suitable stability properties. MATERIALS AND METHODS: Three different methods were used to prepare niosome formulations: Dehydration rehydration vesicle method, direct mixing method, homogenizer method. Sorbitan surfactants, cholesterol, polyoxyethylenecetyl, phosphate buffer (pH 7.4), and charge inductive compounds like cetyltrimethylammonium bromide were used to provide a net negative charge to the final membrane structure. A high-performance liquid chromatography method was then used for the determination of the loaded DEET. RESULTS: A large number of niosomes were multi-layered and have a spherical shape. In comparison, syringe method against direct mixing is more appropriate because of creation MLV and uniform niosomes but the best method is homogenizer method. Drug entrapment was between 14% and 21% in selected formulation. CONCLUSION: According to this study, homogenizing method can be used for formulation of DEET in niosome form in topical formulations. PMID- 26682197 TI - Development of novel multifunction directly compressible co-processed excipient by melt granulation technique. AB - INTRODUCTION: The objective of the present investigation was to develop a novel multifunctional directly compressible co-processed excipient consisting of dibasic calcium phosphate anhydrous, polyethylene glycol 4000 (PEG 4000) and crospovidone using Box-Behnken design. MATERIALS AND METHODS: The technique of melt granulation was adopted for the preparation of the co-processed excipient. The percentage of crospovidone (5-10% w/w), percentage of PEG 4000 (5-15% w/w) and the heating time (4-12 min) were selected as independent variables. The co processed granules were evaluated for bulk density, tapped density, Hausner's ratio and Carr's index. Placebo tablets of co-processed granules were prepared and evaluated for hardness, friability and disintegration time. Multiple linear regression was applied to develop mathematical models for hardness, Carr' index and disintegrating time. ANOVA was applied to study the fitting and significance of the model. The optimized batches (BB) were selected for further studies. The selected batches were characterized for particle size distribution, granular friability index, moisture uptake study, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. Aceclofenac was selected as model drug for the preparation of tablets. RESULTS: Aceclofenac tablets prepared using co-processed excipients showed better hardness, disintegration time and in vitro drug release as compared to aceclofenac tablets prepared using conventional wet granulation method. CONCLUSION: The developed co-processed excipient can serve as a novel co processed excipient for improvement of tableting characteristics. PMID- 26682198 TI - Modified extrusion-spheronization as a technique of microencapsulation for stabilization of choline bitartrate using hydrogenated soya bean oil. AB - INTRODUCTION: Choline bitartrate (CBT) is a vital nutrient for fetal brain development and memory function. It is hygroscopic in nature which is associated with stability related problem during storage such as development of fishy odor and discoloration. AIM: Microencapsulation method was adopted to resolve the stability problem and for this hydrogenated soya bean oil (HSO) was used as encapsulating agent. MATERIALS AND METHODS: Industrially feasible modified extrusion-spheronization technique was selected for microencapsulation. HSO was used as encapsulating agent, hydroxypropyl methyl cellulose E5/E15 as binder and microcrystalline cellulose as spheronization aid. Formulated pellets were evaluated for parameters such as flow property, morphological characteristics, hardness-friability index (HFI), drug content, encapsulation efficiency, and in vitro drug release. The optimized formulations were also characterized for particle size (by laser diffractometry), differential scanning calorimetry, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy, and scanning electron microscopy. RESULTS AND DISCUSSIONS: The results from the study showed that coating of 90% and 60% CBT was successful with respect to all desired evaluation parameters. Optimized formulation was kept for 6 months stability study as per ICH guidelines, and there was no change in color, moisture content, drug content, and no fishy odor was observed. CONCLUSION: Microencapsulated pellets of CBT using HSO as encapsulating agent were developed using modified extrusion spheronization technique. Optimized formulations, CBT 90% (F5), and CBT 60% (F10), were found to be stable for 4M and 6M, respectively, at accelerated conditions. PMID- 26682199 TI - Proteolytic Activities Expressed by Gastrointestinal Pathogens Bacillus cereus, Listeria monocytogenes and Enterococcus faecium in Different Growth Phases. AB - AIMS: Bacterial proteases are implicated in protein quality control, biofilm formation or might have a direct function in pathogenesis by processing virulence factors or cleaving host factors. In recent years, knowledge of proteases expressed by Gram-negative pathogens remarkably increased. However, investigation of proteases from Gram-positive bacteria is rather rare, but required for the analysis of pathogenesis-relevant proteases. In this study, we extracted and detected proteases from the gastrointestinal pathogens Bacillus cereus, Listeria monocytogenes, and Enterococcus faecium in different growth phases. METHODOLOGY: Bacteria were grown to logarithmic or stationary phases, harvested and extracted by sonication and French press. For the detection of active proteases, zymography analyses were performed using casein and gelatin as substrates to monitor caseinolytic and gelatinolytic activities. RESULTS: We observed different active proteases with different intensities in bacteria grown to logarithmic or stationary phases. Strong activities as gelatinases were detected in B. cereus and distinct caseinolytic proteases exhibiting molecular weights of > 170 kDa, 70 kDa and 45 kDa were shown in L. monocytogenes and E. faecium, respectively. Interestingly, detected proteases were differentially regulated in bacteria grown to logarithmic or stationary phases. CONCLUSION: In summary, the data clearly indicated proteases that are differentially regulated in the Gram-positive pathogens B. cereus, L. monocytogenes, and E. faecium, which might contribute to bacterial pathogenesis. PMID- 26682200 TI - THE PRACTICE OF THE INTEGRATED PREVENTION. AB - Our study regarding the theoretical and practical aspects of the integrated prevention is based on a specific methodological design and analysis of the gathered data. However, our main goal it's not the communication of the quantitative results, instead we intend to formulate the theoretical conclusions that can be deriving from our analyses. Our data were gathered through analyses last for more than two decades, applying questionnaires, interviewing and focus group experiences regarding the problematic of drug consuming, and our goal is to raise this information to a level of theoretical conceptualization. The actuality of our study is given by the fact that data provided by both our research and international literature show that deviances, including the frequency of drug use is manifesting an ascendant trend. Topics about prevention are present among the resources and discussions in home specialty literature for decades, in campaigns or rather sporadically. However, we can observe a lack of regional or national coordination, and planned collaborative prevention practices. In the same time, we rarely find an aggregation and summarized interpretation of the national research data, which allows the translation of them into theoretical models. Our goal is to fill this gap through our analyses. We believe that only prevention programs that are adapted to the local conditions and socio-cultural environment will show a relevant efficiency. Nowadays, they are being used the same universal programs from America to Europe. In our study, we perform to a theoretical explanation of prevention, this way raising the possibility of an attitude change, and the establishment of a national data-based preventative approach. In our approach, we integrate the concepts present in the international literature of prevention. Furthermore, we are subtracting those conclusions on which bases the prevention can be interpreted as a tool for community mental health and sharing those aspects that contribute to the design and implementation of efficient prevention. We also provide theoretical models serving the design and the implementation process of prevention, besides introducing a new concept: the designation of integrated prevention, based on our analyses. PMID- 26682201 TI - Association between retinal nerve fiber layer thickness and magnetic resonance imaging findings and intelligence in patients with multiple sclerosis. AB - BACKGROUND: Multiple Sclerosis (MS) is a neurological disease in which demyelination and axonal loss leads to progressive disability. Cognition impairment is among the most common complication. Studying axonal loss in the retina is a new marker for MS. The main goal of our study is to search for correlations between magnetic resonance imaging (MRI) findings and the retinal nerve fiber layer (RNFL) thickness at the macula and head of the optic nerve and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Scores that assess multiple domains of intelligence, and to explore the relationship between changes in the RNFL thickness with intellectual and cognitive dysfunction. MATERIALS AND METHODS: A prospective cross-sectional study was conducted at the University Hospital of Kashani, Isfahan, Iran, from September to December 2013. All patients were assessed with a full-scale intelligence quotient (IQ) on the WAIS-R. An optical coherence tomography study and brain MRI were performed in the same week for all the patients. Statistical analysis was conducted by using a bivariate correlation, by utilizing SPSS 20.0. A P value <= 0.05 was the threshold of statistical significance. RESULTS: Examination of a 100 patients showed a significant correlation between the average RNFL thickness of the macula and the verbal IQ (P value = 0.01) and full IQ (P value = 0.01). There was a significant correlation between brain atrophy and verbal IQ. CONCLUSION: The RNFL loss was correlated with verbal IQ and full IQ. PMID- 26682202 TI - Elimination of routine chest radiographs following off-pump coronary artery bypass surgery: A randomized controlled trial study. AB - BACKGROUND: Post cardiac surgery routine chest radiographs (CXRs), ordered without any clinical and laboratory indications, is a standard obligatory practice in many cardiothoracic centers. Routine CXRs incur cost, manpower, and radiation. The objective of this study is to assess early outcome in off-pump coronary artery bypass (OPCAB) patients with postoperative routine versus clinically indicated CXR protocols. MATERIALS AND METHODS: This study is a randomized clinical trial conducted on 231 OPCAB candidates in Afshar Cardiac Center, Yazd, Iran. Patients were categorized into two groups. All 118 patients in group A had routine postoperative CXRs. The 113 patients in group B were selectively exposed to CXR only on clinical indications. All patients were postoperatively followed up for 30 days. Data gathered from both groups were statistically analyzed. RESULTS: Routine postoperative CXRs obtained in 118 OPCAB group A candidates showed abnormal findings in 20 patients that did not require new intervention. One month follow-up of these patients showed no complications. In 113 OPCAB candidates of group B, 7 on-demand CXRs were obtained on clinical evaluation that required added intervention. In a 1-month follow-up of this group, five patients presented with symptomatic complaints. On re-examination, none needed readmission, intervention, or paraclinical evaluation. No complications were observed due to CXR elimination. CONCLUSION: The study suggests that postoperative CXR selected on clinical grounds in place of routine CXR does not change early postoperative outcome of OPCAB procedure. PMID- 26682203 TI - Blood transfusion safety: A study of adverse reactions at the blood bank of a tertiary care center. AB - BACKGROUND: An adverse transfusion reaction (ATR) is an unfavorable reaction to the transfused unit, the severity of which may be different among individuals depending upon the type of reaction and the patient's susceptibility. Transfusion reactions may be immediate or delayed type depending on the onset and immune or nonimmune type depending on the pathogenesis. A study was conducted to study the frequency of various transfusion reactions and the associated morbidity. MATERIALS AND METHODS: All ATRs occurring over a period of 3 years at a tertiary care health center were studied in detail according to the institute's protocol. RESULTS: Of 38,013 units of blood and components that had been issued, 101 (0.2%) cases had an ATR. The most common reaction was allergic - 34/101 (33.6%) followed by febrile - 26/101 (25.7%). Other reactions included transfusion-related acute lung injury in 6/101 (5.9%) cases, and immune reactions were seen in 19/101 (18.8%) cases. CONCLUSION: Allergic and febrile reactions are most common and least harmful, but fatal reactions can also occur, and preventive measures must be taken to avoid such reactions. PMID- 26682204 TI - Effect of increase in duration of aprepitant consumption from 3 to 6 days on the prevention of nausea and vomiting in women receiving combination of anthracycline/cyclophosphamide chemotherapy: A randomized, crossover, clinical trial. AB - BACKGROUND: Aprepitant is one of the effective antiemetic drugs that usually used for a period of 3 days for prevention of anthracycline/cyclophosphamide (AC) induced nausea and vomiting. However, many patients still experience nausea and vomiting on days 3-5. The aim of this study was to evaluate the effect of an increase in duration of aprepitant consumption from 3 to 6 days on the prevention of nausea and vomiting in women receiving AC chemotherapy. MATERIALS AND METHODS: It was a randomized, crossover, controlled clinical trial. Women with breast cancer and scheduled to receive AC regimens were enrolled in this study. Enrolled patients were randomized into two groups. Group I received 3 days regimen of aprepitant in the first course of AC regimen chemotherapy and 6 days regimen of aprepitant in the second course; Group II received 6 days regimen followed by 3 days regimen. For nausea and vomiting assessment, we used Eastern Cooperative Oncology Group questionnaire. RESULTS: Forty-nine patients were enrolled in this study. Sixty-three percent achieved a complete response with 6 days aprepitant regimen compared with 39% with 3 days regimen (P < 0.001). Ten percent had at least one vomiting episode during the 6 days regimen versus 15% with 3 days regimen (P = 0.034). Nausea was significantly more severe in 3 days regimen of aprepitant than in 6 days regimen. CONCLUSION: Increase in the duration of aprepitant consumption through 6 days resulted in significantly better prevention of nausea and vomiting than 3 days consumption for women receiving AC chemotherapy. PMID- 26682205 TI - Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology. AB - BACKGROUND: This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 3(2) full factorial design. MATERIALS AND METHODS: Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers - HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations. RESULTS: The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process. DISCUSSION: The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM. PMID- 26682206 TI - Precalcitonin and C-reactive protein as markers in response to antibiotic treatment in ventilator-associated pneumonia in intensive care unit-hospitalized patients. AB - BACKGROUND: Pneumonia due to ventilator is a prevalent nosocomial infection associated with high morbidity and mortality. This study aimed to determine the change in serum levels of precalcitonin (PCT) and C-reactive protein (CRP) in response to antibiotic treatment in patients hospitalized in intense care unit (ICU) suffering from ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: This is an analytical and descriptive study performed in 2013 in Ayatollah Kashani Medical Training Center, Isfahan, Iran. The statistical sample includes patients hospitalized in ICU in 2013 suffering from VAP. In this study, 50 patients suffering from VAP were selected, and PCT and CRP levels were measured in them before antibiotic therapy and every 48 h until the end of therapy. The collected data were analyzed by SPSS software. RESULTS: CRP and PCT levels were high before the beginning of antibiotic therapy in all patients suffering from VAP and their CRP level had an increasing trend until 4 days after the beginning of therapy; however, from the 4(th) day, it turned into decreasing trend. PCT serum level was higher than normal before the treatment and until 48 h after the therapy, and then it was found to have a decreasing trend. According to variance analysis test with repetition of observations, the mean level of mentioned markers had a meaningful difference before the beginning of antibiotic therapy until the end of antibiotic therapy (P < 0.001). CONCLUSION: CRP and PCT serum levels can be used as an instrument for determining the effect of antibiotic therapy in patients with VAP. PMID- 26682207 TI - Study of oxidants and antioxidants in patients of acute myocardial infarction. AB - BACKGROUND: Oxygen free radicals have become attractive candidates to explain injuries in ischemic heart. An association between raised serum uric acid concentration and increased cardiovascular risk has been recognized, however its role in acute myocardial infarction (AMI) is still unclear. Recently, zinc is also trying to establish its role in tissue injury and oxidative stress. MATERIALS AND METHODS: This cross-sectional study was carried on 75 AMI patients. 5 ml of blood was drawn from each patient within 6 h of AMI, to estimate plasma malondialdehyde (MDA), serum zinc, whole blood superoxide desmutase, serum uric acid, and whole blood glutathione peroxidase (GPx). The same biochemicals were also determined in 50 age and gender matched controls for comparison. RESULTS: We found significantly increased level of plasma MDA (5.649 +/- 0.1780 vs. 2.757 +/- 0.1623), serum uric acid (4.533 +/- 0.1526 vs. 3.200 +/- 0.1616) and significantly decreased levels of serum zinc (104.5 +/- 1.874 vs. 115.3 +/- 3.077), whole blood GPx (4599 +/- 101.1 vs. 5519 +/- 81.63) and superoxide desmutase (166.8 +/- 1.896 vs. 188.3 +/- 4.120). All the parameters studied also showed similar significant changes in male and female cases separately. CONCLUSION: Raised MDA and decreased zinc, glutathione peroxidase, and superoxide desmutase levels denote the increased oxidative stress. Even being a defense, uric acid is raised as it is abundantly present in our body. Thus, AMI exhibits oxidative stress dependent changes irrespective of gender. PMID- 26682208 TI - Evaluation the effect of 17-alpha hydroxyprogesterone caproate on gestational diabetes mellitus in pregnant women at risk for preterm birth. AB - BACKGROUND: The mellitus exact role of 17-alpha hydroxyprogesterone caproate in increasing the rate of gestational diabetes mellitus (GDM) is still unclear. This study was aimed to investigate the association of treatment with 17-alpha hydroxyprogesterone caproate with GDM in pregnant women who are at risk for preterm birth (PTB). MATERIALS AND METHODS: In this clinical trial, 200 singleton pregnant women included 100 pregnant women at risk for PTB or with history of PTB as case group (received weekly injections of 17-alpha hydroxyprogesterone caproate) and 100 healthy pregnant women without history of PTB as control group (did not receive any drug) were evaluated. All women followed until detect or reject of GDM, and abnormal glucose challenge test (GCT) and GDM were calculated in all of them. RESULTS: During study follow-up, 36 women in both groups were excluded and 81 cases 83 controls completed the study and analyzed. Mean of GCT in all studied pregnant women was 128.2 +/- 18.1, whereas, in cases was higher than controls but no significant difference was noted between groups (P = 0.56). Abnormality in GCT was observed in 32 (19.5%) of 164 studied women, (18 of cases and 14 of controls), which was not statistically significant (P = 0.34). The frequency of GDM among all studied women was 7.9% (13 of 164), 7 of cases and 6 of controls, which was not significant (P = 0.74). CONCLUSION: In summary, results demonstrated that weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of GDM in pregnant women at risk for PTB. PMID- 26682209 TI - Design and expression of fusion protein consists of HBsAg and Polyepitope of HCV as an HCV potential vaccine. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a serious public health threat worldwide. Cellular immune responses, especially cytotoxic T-lymphocytes (CTLs), play a critical role in immune response toward the HCV clearance. Since polytope vaccines have the ability to stimulate the cellular immunity, a recombinant fusion protein was developed in this study. MATERIALS AND METHODS: The designed fusion protein is composed of hepatitis B surface antigen (HBsAg), as an immunocarrier, fused to an HCV polytope sequence. The polytope containing five immunogenic epitopes of HCV was designed to induce specific CTL responses. The construct was cloned into the pET-28a, and its expression was investigated in BL21 (DE3), BL21 pLysS, BL21 pLysE, and BL21 AI Escherichia coli strains using 12% gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Finally, the identity of expressed fusion protein was confirmed by Western blotting using anti His monoclonal antibody and affinity chromatography was applied to purify the expressed protein. RESULTS: The accuracy of the construct was confirmed by restriction map analysis and sequencing. The transformation of the construct into the BL21 (DE3), pLysS, and pLysE E. coli strains did not lead to any expression. The fusion protein was found to be toxic for E. coli DE3. By applying two steps inhibition, the fusion protein was successfully expressed in BL21 (AI) E. coli strain. CONCLUSION: The HBsAg-polytope fusion protein expressed in this study can be further evaluated for its immunogenicity in animal models. PMID- 26682210 TI - Genetic Regulation of Sinoatrial Node Development and Pacemaker Program in the Venous Pole. AB - The definitive sinoatrial node (SAN), the primary pacemaker of the mammalian heart, develops from part of pro-pacemaking embryonic venous pole that expresses both Hcn4 and the transcriptional factor Shox2. It is noted that ectopic pacemaking activities originated from the myocardial sleeves of the pulmonary vein and systemic venous return, both derived from the Shox2+ pro-pacemaking cells in the venous pole, cause atrial fibrillation. However, the developmental link between the pacemaker properties in the embryonic venous pole cells and the SAN remains largely uncharacterized. Furthermore, the genetic program for the development of heterogeneous populations of the SAN is also under-appreciated. Here, we review the literature for a better understanding of the heterogeneous development of the SAN in relation to that of the sinus venosus myocardium and pulmonary vein myocardium. We also attempt to revisit genetic models pertinent to the development of pacemaker activities in the perspective of a Shox2-Nkx2-5 epistatic antagonism. Finally, we describe recent efforts in deciphering the regulatory networks for pacemaker development by genome-wide approaches. PMID- 26682211 TI - The Use of Physical Restraint in Norwegian Adult Psychiatric Hospitals. AB - Background. The use of coercion within the psychiatric services is problematic and raises a range of ethical, legal, and clinical questions. "Physical restraint" is an emergency procedure used in psychiatric hospitals to control patients that pose an imminent physical danger. We wished to review the literature published in scientific peer-reviewed journals describing studies on the use of physical restraint in Norway, in order to identify the current state of knowledge and directions for future research. Design. The databases PubMed, PsycINFO, CINAHL, Web of Science, and Embase were searched for studies relating to physical restraint (including holding) in Norwegian psychiatric hospitals, supplemented with hand searches. Results. 28 studies were included. Most of the studies were on rates of restraint, but there were also some studies on perceptions of patients and staff, case studies, and ethnographic studies. There was only one intervention study. There are differences in use between wards and institutions, which in part may be explained by differences in patient populations. Staff appear to be less negative to the use of restraint than patients. Conclusions. The studies that were identified were primarily concerned with rates of use and with patients' and staff's perspectives. More interventional studies are needed to move the field forward. PMID- 26682212 TI - Predicting 30-Day Readmissions: Performance of the LACE Index Compared with a Regression Model among General Medicine Patients in Singapore. AB - The LACE index (length of stay, acuity of admission, Charlson comorbidity index, CCI, and number of emergency department visits in preceding 6 months) derived in Canada is simple and may have clinical utility in Singapore to predict readmission risk. We compared the performance of the LACE index with a derived model in identifying 30-day readmissions from a population of general medicine patients in Singapore. Additional variables include patient demographics, comorbidities, clinical and laboratory variables during the index admission, and prior healthcare utilization in the preceding year. 5,862 patients were analysed and 572 patients (9.8%) were readmitted in the 30 days following discharge. Age, CCI, count of surgical procedures during index admission, white cell count, serum albumin, and number of emergency department visits in previous 6 months were significantly associated with 30-day readmission risk. The final logistic regression model had fair discriminative ability c-statistic of 0.650 while the LACE index achieved c-statistic of 0.628 in predicting 30-day readmissions. Our derived model has the advantage of being available early in the admission to identify patients at high risk of readmission for interventions. Additional factors predicting readmission risk and machine learning techniques should be considered to improve model performance. PMID- 26682213 TI - Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae. AB - Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m(3) of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m(3) ethanol/year. PMID- 26682214 TI - Circadian Control of Global Transcription. AB - Circadian rhythms exist in most if not all organisms on the Earth and manifest in various aspects of physiology and behavior. These rhythmic processes are believed to be driven by endogenous molecular clocks that regulate rhythmic expression of clock-controlled genes (CCGs). CCGs consist of a significant portion of the genome and are involved in diverse biological pathways. The transcription of CCGs is tuned by rhythmic actions of transcription factors and circadian alterations in chromatin. Here, we review the circadian control of CCG transcription in five model organisms that are widely used, including cyanobacterium, fungus, plant, fruit fly, and mouse. Comparing the similarity and differences in the five organisms could help us better understand the function of the circadian clock, as well as its output mechanisms adapted to meet the demands of diverse environmental conditions. PMID- 26682215 TI - Hypoglycemic and Antidiabetic Effect of Pleurotus sajor-caju Aqueous Extract in Normal and Streptozotocin-Induced Diabetic Rats. AB - INTRODUCTION: Pleurotus sajor-caju (PSC) is an edible oyster mushroom featuring high nutritional values and pharmacological properties. Objective. To investigate the hypoglycemic and antidiabetic effects of single and repeated oral administration of PSC aqueous extract in normal and diabetic rats. MATERIALS AND METHODS: A single dose of 500, 750, or 1000 mg/kg of the PSC extract was given to experimental rats to determine the effects on blood glucose (BG) and oral glucose tolerance test (OGTT). The effective dose (750 mg/kg) of PSC extract was repeatedly administrated daily for 21 days in diabetic rats to examine its antidiabetic effects in terms of BG control, body weight, urine sugar, HbA1c, and several serum profiles. RESULTS: The dose of 750 mg/kg showed the most significant BG reduction (23.5%) in normal rats 6 hours after administration in BG study (p < 0.05). In OGTT study, the same dose produced a maximum BG fall of 41.3% in normal rats and 36.5% in diabetic rats 3 hours after glucose administration. In 21-day study, treated diabetic rats showed significant improvement in terms of fasting BG, body weight, and urine sugar as compared to control diabetic rats. CONCLUSION: The study evidenced scientifically the beneficial use of PSC as an alternative medicine in diabetes management. PMID- 26682216 TI - Emerging Threats for Human Health in Poland: Pathogenic Isolates from Drug Resistant Acanthamoeba Keratitis Monitored in terms of Their In Vitro Dynamics and Temperature Adaptability. AB - Amphizoic amoebae generate a serious human health threat due to their pathogenic potential as facultative parasites, causative agents of vision-threatening Acanthamoeba keratitis (AK). Recently, AK incidences have been reported with increasing frequency worldwide, particularly in contact lens wearers. In our study, severe cases of AK in Poland and respective pathogenic isolates were assessed at clinical, morphological, and molecular levels. Misdiagnoses and the unsuccessful treatment in other ophthalmic units delayed suitable therapy, and resistance to applied chemicals resulted in severe courses and treatment difficulties. Molecular assessment indicated that all sequenced pathogenic corneal isolates deriving from Polish patients with AK examined by us showed 98 100% homology with Acanthamoeba genotype T4, the most prevalent genotype in this human ocular infection worldwide. In vitro assays revealed that the pathogenic strains are able to grow at elevated temperature and have a wide adaptive capability. This study is our subsequent in vitro investigation on pathogenic Acanthamoeba strains of AK originating from Polish patients. Further investigations designed to foster a better understanding of the factors leading to an increase of AK observed in the past years in Poland may help to prevent or at least better cope with future cases. PMID- 26682217 TI - The Effect of Dimethyl Sulfoxide on Supercoiled DNA Relaxation Catalyzed by Type I Topoisomerases. AB - The effects of dimethyl sulfoxide (DMSO) on supercoiled plasmid DNA relaxation catalyzed by two typical type I topoisomerases were investigated in our studies. It is shown that DMSO in a low concentration (less than 20%, v/v) can induce a dose-related enhancement of the relaxation efficiency of Escherichia coli topoisomerase I (type IA). Conversely, obvious inhibitory effect on the activity of calf thymus topoisomerase I (type IB) was observed when the same concentration of DMSO is used. In addition, our studies demonstrate that 20% DMSO has an ability to reduce the inhibitory effect on EcTopo I, which was induced by double stranded oligodeoxyribonucleotides while the same effect cannot be found in the case of CtTopo I. Moreover, our AFM examinations suggested that DMSO can change the conformation of negatively supercoiled plasmid by creating some locally loose regions in DNA molecules. Combining all the lines of evidence, we proposed that DMSO enhanced EcTopo I relaxation activity by (1) increasing the single-stranded DNA regions for the activities of EcTopo I in the early and middle stages of the reaction and (2) preventing the formation of double-stranded DNA-enzyme complex in the later stage, which can elevate the effective concentration of the topoisomerase in the reaction solution. PMID- 26682218 TI - Effects of Shared Electronic Health Record Systems on Drug-Drug Interaction and Duplication Warning Detection. AB - Shared electronic health records (EHRs) systems can offer a complete medication overview of the prescriptions of different health care providers. We use health claims data of more than 1 million Austrians in 2006 and 2007 with 27 million prescriptions to estimate the effect of shared EHR systems on drug-drug interaction (DDI) and duplication warnings detection and prevention. The Austria Codex and the ATC/DDD information were used as a knowledge base to detect possible DDIs. DDIs are categorized as severe, moderate, and minor interactions. In comparison to the current situation where only DDIs between drugs issued by a single health care provider can be checked, the number of warnings increases significantly if all drugs of a patient are checked: severe DDI warnings would be detected for 20% more persons, and the number of severe DDI warnings and duplication warnings would increase by 17%. We show that not only do shared EHR systems help to detect more patients with warnings but DDIs are also detected more frequently. Patient safety can be increased using shared EHR systems. PMID- 26682219 TI - Haemodynamic Effects of Lung Recruitment Manoeuvres. AB - Atelectasis caused by lung injury leads to increased intrapulmonary shunt, venous admixture, and hypoxaemia. Lung recruitment manoeuvres aim to quickly reverse this scenario by applying increased airway pressures for a short period of time which meant to open the collapsed alveoli. Although the procedure can improve oxygenation, but due to the heart-lung and right and left ventricle interactions elevated intrathoracic pressures can inflict serious effects on the cardiovascular system. The purpose of this paper is to give an overview on the pathophysiological background of the heart-lung interactions and the best way to monitor these changes during lung recruitment. PMID- 26682221 TI - MatPred: Computational Identification of Mature MicroRNAs within Novel Pre MicroRNAs. AB - BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs integral for regulating gene expression at the posttranscriptional level. However, experimental methods often fall short in finding miRNAs expressed at low levels or in specific tissues. While several computational methods have been developed for predicting the localization of mature miRNAs within the precursor transcript, the prediction accuracy requires significant improvement. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present MatPred, which predicts mature miRNA candidates within novel pre-miRNA transcripts. In addition to the relative locus of the mature miRNA within the pre miRNA hairpin loop and minimum free energy, we innovatively integrated features that describe the nucleotide-specific RNA secondary structure characteristics. In total, 94 features were extracted from the mature miRNA loci and flanking regions. The model was trained based on a radial basis function kernel/support vector machine (RBF/SVM). Our method can predict precise locations of mature miRNAs, as affirmed by experimentally verified human pre-miRNAs or pre-miRNAs candidates, thus achieving a significant advantage over existing methods. CONCLUSIONS: MatPred is a highly effective method for identifying mature miRNAs within novel pre-miRNA transcripts. Our model significantly outperformed three other widely used existing methods. Such processing prediction methods may provide important insight into miRNA biogenesis. PMID- 26682220 TI - Serum Levels of ApoA1 and ApoA2 Are Associated with Cognitive Status in Older Men. AB - Background. Advancing age, chronic inflammation, oxidative damage, and disorders of lipid metabolism are positively linked to the late-life cognitive impairment. Serum biomarkers may be associated with the cognitive status in older men. Methods. 440 old male subjects with different cognitive functions were recruited to investigate probable serum markers. Pearson Chi-Squared test, univariate analysis, and multivariate logistic regression analysis were performed to evaluate biomarkers which may be associated with cognitive status. Results. Levels of fundus atherosclerosis (AS) (P < 0.001), age (P < 0.001), serum biomarkers peroxidase (POD) (P = 0.026) and interleukin-6 (IL-6) (P = 0.001), serum levels of high-density lipoprotein cholesterol (HDL-C) (P < 0.001), apolipoprotein A2 (ApoA2) (P = 0.001), and ApoC2 (P = 0.005) showed significant differences. Compared to group 3, ApoA1 in group 1 (OR = 1.30, 95% CI 1.01-1.67) and group 2 (OR = 1.47, 95% CI 1.11-1.94) were higher, while ApoA2 were lower (group 1: OR = 0.43, 95% CI 0.18-1.02; group 2: OR = 0.21, 95% CI 0.08-0.54) after adjusting for control variables. Conclusion. The results demonstrated that age, AS levels, POD, IL-6, HDL-C, ApoA2, and ApoC2 were significantly related to cognitive status. Moreover, ApoA1 and ApoA2 were independently associated with cognitive impairment and late-life dementia. PMID- 26682222 TI - Risk Factors for Emergency Department Short Time Readmission in Stratified Population. AB - BACKGROUND: Emergency department (ED) readmissions are considered an indicator of healthcare quality that is particularly relevant in older adults. The primary objective of this study was to identify key factors for predicting patients returning to the ED within 30 days of being discharged. METHODS: We analysed patients who attended our ED in June 2014, stratified into four groups based on the Kaiser pyramid. We collected data on more than 100 variables per case including demographic and clinical characteristics and drug treatments. We identified the variables with the highest discriminating power to predict ED readmission and constructed classifiers using machine learning methods to provide predictions. RESULTS: Classifier performance distinguishing between patients who were and were not readmitted (within 30 days), in terms of average accuracy (AC). The variables with the greatest discriminating power were age, comorbidity, reasons for consultation, social factors, and drug treatments. CONCLUSIONS: It is possible to predict readmissions in stratified groups with high accuracy and to identify the most important factors influencing the event. Therefore, it will be possible to develop interventions to improve the quality of care provided to ED patients. PMID- 26682223 TI - Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors. AB - Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients. PMID- 26682224 TI - Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization. AB - Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a physicochemical characterization of a biosimilar trastuzumab focused on the attributes related to the pharmacokinetic response. Capillary isoelectrofocusing (cIEF) and cation exchange chromatography (CEX) were used to evaluate charge heterogeneity; glycosylation profiles were assessed through hydrophilic interaction liquid chromatography (HILIC); aggregates content was evaluated through size exclusion chromatography (SEC) while binding affinity to FcRn was evaluated using isothermal titration calorimetry (ITC). The biosimilar trastuzumab and its reference product exhibited a high degree of similarity for the evaluated attributes. In regard to the pharmacokinetic parameters, randomized, double blind, and two-arm parallel and prospective study was employed after the administration of a single intravenous dose in healthy volunteers. No significant differences were found between the pharmacokinetic profiles of both products. Our results confirm that similarity of the critical quality attributes between a biosimilar product, obtained from a different manufacturing process, and the reference product resulted in comparable pharmacokinetic profiles, diminishing the uncertainty related to the biosimilar's safety and efficacy. PMID- 26682225 TI - Defining Multimorbidity: From English to Portuguese Using a Delphi Technique. AB - OBJECTIVE: To translate the European General Practice Research Network multimorbidity definition according to Portuguese cultural and linguistic features. METHODS: Similar to the process completed in several other European countries, a forward and backward translation of the English multimorbidity definition using the Delphi technique was performed in Portugal. RESULTS: Twenty three general practitioners (GPs)-14 males and 9 females-agreed to form the Portuguese expert panel for the Delphi process (59% acceptance rate). The Portuguese definition of multimorbidity was achieved after two Delphi rounds with a mean (SD) consensus score for final round of 8.43/9 (0.73). CONCLUSION: With this paper the definition of multimorbidity is now available in a new language Portuguese. Its availability in the local language will raise Portuguese GPs' awareness about multimorbidity and allow future national and international research. The operationalization of the definition will allow an easier identification of patients with multimorbidity. PMID- 26682226 TI - The Impact of an Internet-Based Self-Management Intervention (HeLP-Diabetes) on the Psychological Well-Being of Adults with Type 2 Diabetes: A Mixed-Method Cohort Study. AB - This mixed-method study assessed the impact of an internet-based, self-management intervention ("HeLP-Diabetes") on the psychological well-being of adults with type 2 diabetes. Nineteen participants were recruited from 3 general practices. Data were collected at baseline and at 6 weeks follow-up. Access to HeLP-Diabetes was associated with a significant decrease in participants' diabetes-related distress (Z = 2.04, p = 0.04, and d = 0.28). No significant differences were found in emotional distress or self-efficacy. The qualitative data found that participants reported improvements including increased self-efficacy and support, better management of low mood, greater diabetes awareness, and taking the condition more seriously. Participants also reported making improvements to their eating habits, exercise routine, and medical management. Some negative experiences associated with using the intervention were mentioned including feelings of guilt for not using the intervention as suggested or not making any behavioral changes, as well as technical and navigational frustrations with the intervention. Internet-based self-management interventions may have the potential to decrease diabetes-related distress in people with type 2 diabetes. The qualitative data also suggests internet interventions can positively impact both psychological and behavioural outcomes of adults with type 2 diabetes. PMID- 26682227 TI - Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen. AB - Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk. PMID- 26682229 TI - Working Together to Promote Diabetes Control: A Practical Guide for Diabetes Health Care Providers in Establishing a Working Alliance to Achieve Self Management Support. AB - The quality of the "patient-carer" relationship is the foundation of self management support and has been shown to influence treatment outcome in relation to psychological and somatic illness, including diabetes. It has long been accepted within applied psychology that the quality of the client-therapist relationship--termed the working alliance--is of central importance to treatment outcome and may account for a significant degree of the overall treatment effect. Diabetes healthcare providers have recently expressed a need for further training in communication techniques and in the psychological aspects of diabetes. Could we take a page from the psychological treatment manual on working alliance in therapy to guide the diabetes healthcare provider in their role of supporting the person with diabetes achieve and maintain better metabolic control? This paper examines the role of the working alliance in diabetes care and offers a practical guide to the diabetes healthcare provider in establishing a working alliance with the person with diabetes in managing diabetes. PMID- 26682230 TI - Low Self-Confidence and Diabetes Mismanagement in Youth with Type 1 Diabetes Mediate the Relationship between Behavioral Problems and Elevated HbA1c. AB - INTRODUCTION: Previous studies indicated an association between behavior problems (internalizing, externalizing) and glycemic control (HbA1c) in youth with type 1 diabetes (T1D). The aim of this study is to examine if this association is mediated by self-confidence and mismanagement of diabetes. METHODS: Problem behavior was assessed with the Strengths and Difficulties Questionnaire. Mediating variables were assessed using the Confidence in Diabetes Self-Care Youth and Diabetes Mismanagement Questionnaire. HbA1c was derived from hospital charts. Bootstrap mediation analysis for multiple mediation was utilized. RESULTS: 88 youths with T1D, age 11-15 y, participated. The relation between both overall problem behavior and externalizing behavior problems and HbA1c was mediated through confidence in diabetes self-care and mismanagement (a 1 b 1 + a 2 b 2 path; point estimate = 0.50 BCa CI 95% 0.25-0.85; a 1 b 1 + a 2 b 2 path; point estimate = 0.73 BCa CI 95% 0.36-1.25). CONCLUSIONS: Increased problem behavior in youth with T1D is associated with elevated HbA1c and mediated by low self-confidence and diabetes mismanagement. Screening for problem behavior and mismanagement and assisting young patients in building confidence seem indicated to optimize glycemic control. PMID- 26682231 TI - Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes. AB - BACKGROUND: Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. OBJECTIVE: To explore associations between metabolic control (measured by HbA1c) and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. METHODS: A total of 105 patients (41.9% males) with type 1 diabetes (12-20 years) were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. RESULTS: Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05), the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48), and the coping strategy ventilating negative feelings (-.26, p < .05). Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (beta .48, p < .001). None of the variables were significantly associated with HbA1c among males. CONCLUSIONS: Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes. PMID- 26682233 TI - Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways. AB - Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) environment for 3 days, followed by treatment with CoQ10 (10 MUM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID- 26682232 TI - Demographical, Clinical, and Psychological Characteristics of Users and Nonusers of an Online Platform for T2DM Patients (e-VitaDM-3/ZODIAC-44). AB - BACKGROUND: Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one's health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. METHODS: A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. RESULTS: 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled "curious" users, and 88 (13.9%) were identified as "active" users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. DISCUSSION: Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140. PMID- 26682228 TI - Participant Experiences in the Environmental Determinants of Diabetes in the Young Study: Common Reasons for Withdrawing. AB - BACKGROUND: To characterize participant reasons for withdrawing from a diabetes focused longitudinal clinical observational trial (TEDDY) during the first three study years. METHODS: 8677 children were recruited into the TEDDY study. At participant withdrawal staff recorded any reason parents provided for withdrawal. Reasons were categorized into (1) family characteristics and (2) protocol reasons. Families who informed staff of their withdrawal were classified as active withdrawals (AW); families without a final contact were considered passive withdrawals (PW). RESULTS: Withdrawal was highest during the first study year (n = 1220). Most families were AW (n = 1549; 73.4%). PW was more common in the United States (n = 1001; 37.8%) and among young mothers (p = 0.001). The most frequent protocol characteristic was blood draw (55%) and the most common family reason was not having enough time (66%). The blood draw was more common among female participants; being too busy was more common among males. Both reasons were associated with study satisfaction. CONCLUSIONS: Results suggest that, for families of children genetically at risk for diabetes, procedures that can be painful/frightening should be used with caution. Study procedures must also be considered for the demands placed on participants. Study satisfaction should be regularly assessed as an indicator of risk for withdrawal. PMID- 26682234 TI - Health Related Quality of Life among Omani Men and Women with Type 2 Diabetes. AB - The aim of this study was to explore predictors of health related quality of life (HRQoL) among men and women with type 2 diabetes. This cross-sectional descriptive study consisted of a random sample of 300 adults with type 2 diabetes in a selected public hospital. Euro-QoL and Revised Summary of Diabetes Self-Care Activities scales were used to collect data between January and June 2010. Schooling and ability to manage positively were highly significant predictors of quality of life (QoL) among women as compared to men. Age, prevention of activities of daily living and knowledge/management of diabetes were significant predictors of Health state among women as compared to men. Findings demonstrate that 30.6% (versus 35.7%) of the variance in the total QoL and 14% (versus 23%) of the variance in health state could be explained by personal and clinical characteristics among women and men, respectively. The study underlines the importance for nurse educators to assess HRQoL among men and women and to develop effective self-care management strategies based on personal and clinical characteristics. PMID- 26682235 TI - Correlates of Depressive Symptoms in Older Adults with Diabetes. AB - Investigators examined correlates of depressive symptoms within a sample of older adults with diabetes. Participants completed a structured telephone interview with measures including depressive symptoms, health conditions, cognitive function, and diabetes distress. Correlations and hierarchical linear regression models were utilized to examine bivariate and covariate-adjusted correlates of depressive symptoms. The sample included 246 community-dwelling adults with diabetes (>= 65 years old). In bivariate analyses, African Americans, individuals with specific health issues (neuropathy, stroke, respiratory issues, arthritis, and cardiac issues), and those with higher levels of diabetes distress reported more depressive symptoms. Older age, higher education, more income, and better cognitive function were inversely associated with depressive symptoms. In the final covariate-adjusted regression model, stroke (B = .22, p < .001), cognitive function (B = -.14, p < .01), and higher levels of diabetes-related distress (B = .49, p < .001) each were uniquely associated with more depressive symptoms. Diabetes distress partially mediated the associations between cardiac issues and depressive symptoms and between cognitive function and depressive symptoms. Findings suggest that interventions targeted at helping older adults manage their diabetes-related distress and reducing the likelihood of experiencing additional health complications may reduce depressive symptoms within this population. PMID- 26682237 TI - Structure, form, and meaning in the mental lexicon: evidence from Arabic. AB - Does the organization of the mental lexicon reflect the combination of abstract underlying morphemic units or the concatenation of word-level phonological units? We address these fundamental issues in Arabic, a Semitic language where every surface form is potentially analyzable into abstract morphemic units - the word pattern and the root - and where this view contrasts with stem-based approaches, chiefly driven by linguistic considerations, in which neither roots nor word patterns play independent roles in word formation and lexical representation. Five cross-modal priming experiments examine the processing of morphologically complex forms in the three major subdivisions of the Arabic lexicon - deverbal nouns, verbs, and primitive nouns. The results demonstrate that root and word pattern morphemes function as abstract cognitive entities, operating independently of semantic factors and dissociable from possible phonological confounds, while stem-based approaches consistently fail to accommodate the basic psycholinguistic properties of the Arabic mental lexicon. PMID- 26682238 TI - An assessment of the effects of ectopic gp91phox expression in XCGD iPSC-derived neutrophils. AB - For the treatment of monogenetic hematological disorders, restoration of transgene expression in affected cell populations is generally considered to have beneficial effects. However, X-linked chronic granulomatous disease (XCGD) is unique since the appearance of functional neutrophils in the peripheral blood following hematopoietic stem cell gene therapy is transient only. One contributing factor could be the occurrence of detrimental effects secondary to ectopic gp91phox expression in neutrophils, which has not been formally demonstrated previously. This study uses iPSCs to model XCGD, which allows the process of differentiation to be studied intensely in vitro. Alpharetroviral vectors carrying a ubiquitous promoter were used to drive the "ectopic" expression of codon optimized gp91phox cDNA. In the mature fraction of neutrophils differentiated from transduced XCGD-iPSCs, cellular recovery in terms of gp91phox expression and reactive oxygen species production was abruptly lost before cells had fully differentiated. Most critically, ectopic gp91phox expression could be identified clearly in the developing fraction of the transduced groups, which appeared to correspond with reduced cell viability. It is possible that this impedes further differentiation of developing neutrophils. Therefore, affording cellular protection from the detrimental effects of ectopic gp91phox expression may improve XCGD clinical outcomes. PMID- 26682236 TI - The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling. AB - Therapeutic protein products (TPP) have been widely used to treat a variety of human diseases, including cancer, hemophilia, and autoimmune diseases. However, TPP can induce unwanted immune responses that can impact both drug efficacy and patient safety. The presence of aggregates is of particular concern as they have been implicated in inducing both T cell-independent and T cell-dependent immune responses. We used mathematical modeling to evaluate several mechanisms through which aggregates of TPP could contribute to the development of immunogenicity. Modeling interactions between aggregates and B cell receptors demonstrated that aggregates are unlikely to induce T cell-independent immune responses by cross linking B cell receptors because the amount of signal transducing complex that can form under physiologically relevant conditions is limited. We systematically evaluate the role of aggregates in inducing T cell-dependent immune responses using a recently developed multiscale mechanistic mathematical model. Our analysis indicates that aggregates could contribute to T cell-dependent immune response by inducing high affinity epitopes which may not be present in the nonaggregated TPP and/or by enhancing danger signals to break tolerance. In summary, our computational analysis is suggestive of novel insights into the mechanisms underlying aggregate-induced immunogenicity, which could be used to develop mitigation strategies. PMID- 26682239 TI - Lay attitudes toward deception in medicine: Theoretical considerations and empirical evidence. AB - Background: There is a lack of empirical data on lay attitudes toward different sorts of deception in medicine. However, lay attitudes toward deception should be taken into account when we consider whether deception is ever permissible in a medical context. The objective of this study was to examine lay attitudes of U.S. citizens toward different sorts of deception across different medical contexts. Methods: A one-time online survey was administered to U.S. users of the Amazon "Mechanical Turk" website. Participants were asked to answer questions regarding a series of vignettes depicting different sorts of deception in medical care, as well as a question regarding their general attitudes toward truth-telling. Results: Of the 200 respondents, the majority found the use of placebos in different contexts to be acceptable following partial disclosure but found it to be unacceptable if it involved outright lying. Also, 55.5% of respondents supported the use of sham surgery in clinical research, although 55% claimed that it would be unacceptable to deceive patients in this research, even if this would improve the quality of the data from the study. Respondents supported fully informing patients about distressing medical information in different contexts, especially when the patient is suffering from a chronic condition. In addition, 42.5% of respondents believed that it is worse to deceive someone by providing the person with false information than it is to do so by giving the person true information that is likely to lead them to form a false belief, without telling them other important information that shows it to be false. However, 41.5% believed that the two methods of deception were morally equivalent. Conclusions: Respondents believed that some forms of deception were acceptable in some circumstances. While the majority of our respondents opposed outright lying in medical contexts, they were prepared to support partial disclosure and the use of placebos when it is in the patient's interests or when it is what the person would want. These results support the position that physicians should be allowed a greater degree of authority to make a professional judgment about whether deception might be morally warranted by the circumstances, provided that it doesn't involve outright lying. PMID- 26682240 TI - Molecular network of HCC aggressiveness. PMID- 26682241 TI - Actionability and precision oncology. PMID- 26682242 TI - Calcineurin/CXCR4 in T-ALL. PMID- 26682243 TI - The epigenetic regulator CTCF modulates BCL6 in lymphoma. PMID- 26682244 TI - MTH1 counteracts oncogenic oxidative stress. PMID- 26682245 TI - IL13Ralpha2 signaling in colorectal cancer. PMID- 26682246 TI - RUNX3 methylation and anti-tumor immunity. PMID- 26682247 TI - Cell polarity as a tumor suppressive mechanism. PMID- 26682248 TI - Elafin: a double agent in breast and ovarian cancer. PMID- 26682249 TI - lnc RNAs, hypoxia and metastasis. PMID- 26682250 TI - Linking omentum and ovarian cancer: NO. PMID- 26682251 TI - Targeting MUC4 in pancreatic cancer: miRNAs. PMID- 26682252 TI - Food as a drug. PMID- 26682253 TI - Endogenous Dach1 in cancer. PMID- 26682254 TI - PEPCK in cancer cell starvation. PMID- 26682255 TI - Synthetic lethality in KRas-driven cancer cells created by glutamine deprivation. PMID- 26682256 TI - Stem cell hunt in NHL. PMID- 26682257 TI - Akt-Girdin as oncotarget. PMID- 26682258 TI - Targeting Bcl2 in cancer. PMID- 26682259 TI - Cell lines from circulating tumor cells. PMID- 26682260 TI - Chemotherapy with ceramide in TNBC. PMID- 26682261 TI - Revisiting stroma in pancreatic cancer. PMID- 26682262 TI - Crumbs and Xpd in mitosis. PMID- 26682263 TI - ECO/siRNA nanoparticles and breast cancer metastasis. PMID- 26682264 TI - MIR-491: CDKN2A tumor suppressor co-pilot. PMID- 26682265 TI - Molecular dissection of ependymomas. PMID- 26682266 TI - Breast cancer regulated by Fringe. PMID- 26682267 TI - Post-transcriptional mapping reveals critical regulators of metastasis. PMID- 26682268 TI - Chemosensitization strategies for the treatment of lung cancer. PMID- 26682269 TI - CAF-specific markers: role of the TGFbeta pathway. PMID- 26682270 TI - Heterogeneity of neuroblastoma. PMID- 26682271 TI - FOXP3-microRNA-146-NF-kappaB as oncotarget. PMID- 26682272 TI - EMT in immuno-resistance. PMID- 26682273 TI - MiR-29/Hsp47 in ECM network. PMID- 26682274 TI - Melanoma immunotherapy. PMID- 26682275 TI - TACC3 in personalized medicine. PMID- 26682276 TI - Understanding why aspirin prevents cancer and why consuming very hot beverages and foods increases esophageal cancer risk. Controlling the division rates of stem cells is an important strategy to prevent cancer. AB - Cancer is, in essence, a stem cell disease. The main biological cause of cancer is that stem cells acquire DNA alterations during cell division. The more stem cell divisions a tissue accumulates over a lifetime, the higher is the risk of cancer in that tissue. This explains why cancer is diagnosed millions of times more often in some tissues than in others, and why cancer incidence increases so dramatically with age. It may also explain why taking a daily low-dose aspirin for several years reduces the risk of developing and dying from cancer. Since aspirin use reduces PGE2 levels and PGE2 fuels stem cell proliferation, aspirin may prevent cancer by restricting the division rates of stem cells. The stem cell division model of cancer may also explain why regular consumption of very hot foods and beverages increases the risk of developing esophageal cancer. Given that tissue injury activates stem cell division for repair, the thermal injury associated with this dietary habit will increase esophageal cancer risk by inducing the accumulation of stem cell divisions in the esophagus. Using these two examples, here I propose that controlling the division rates of stem cells is an essential approach to preventing cancer. PMID- 26682277 TI - Selective amino acid restriction therapy (SAART): a non-pharmacological strategy against all types of cancer cells. AB - Metastasis will continue to be an incurable disease for most patients until we develop highly selective anticancer therapies. The development of these therapies requires finding and exploiting major differences between cancer cells and normal cells. Although the sum of the many DNA alterations of cancer cells makes up such a major difference, there is currently no way of exploiting these alterations as a whole. Here I propose a non-pharmacological strategy to selectively kill any type of cancer cell, including cancer stem cells, by exploiting their complete set of DNA alterations. It is based on creating challenging environmental conditions that only cells with undamaged DNAs can overcome. Cell survival requires continuous protein synthesis, which in turn requires adequate levels of 20 amino acids (AAs). If we temporarily restrict specific AAs and keep high levels of others whose deficit triggers proteolysis, we will force cells to activate a variety of genetic programs to obtain adequate levels of each of the 20 proteinogenic AAs. Because cancer cells have an extremely altered DNA that has evolved under particular environmental conditions, they may be unable to activate the genetic programs required to adapt to and survive the new environment. Cancer patients may be successfully treated with a protein-free artificial diet in which the levels of specific AAs are manipulated. Practical considerations for testing and implementing this cheap and universal anticancer strategy are discussed. PMID- 26682278 TI - Conserved E2F mediated metastasis in mouse models of breast cancer and HER2 positive patients. AB - To improve breast cancer patient outcome work must be done to understand and block tumor metastasis. This study leverages bioinformatics techniques and traditional genetic screens to create a novel method of discovering potential contributors of tumor progression with a focus on tumor metastasis. A database of 1172 of expression data from a variety of mouse models of breast cancer was assembled and queried using previously defined oncogenic activity signatures. This analysis revealed high activity of the E2F family of transcription factors in the MMTV-Neu mouse model. A genetic cross of MMTV-Neu mice into an E2F1 null, E2F2 null, or E2F3 heterozygous background revealed significant changes in tumor progression specifically reductions in tumor latency and metastasis with E2F1 or E2F2 loss. These findings were found to be conserved in human HER2 positive patients. Patients with high E2F1 activity were shown to have worse outcomes such as relapse free survival and distant metastasis free survival. This study shows conserved mechanisms of tumor progression in human breast cancer subtypes and analogous mouse models and underlies the importance of increased research into the characterization of and comparisons between mouse and human tumors to identify which mouse models resemble each subtype of human breast cancer. PMID- 26682279 TI - A ceRNA approach may unveil unexpected contributors to deletion syndromes, the model of 5q- syndrome. AB - In genomic deletions, gene haploinsufficiency might directly configure a specific disease phenotype. Nevertheless, in some cases no functional association can be identified between haploinsufficient genes and the deletion-associated phenotype. Transcripts can act as microRNA sponges. The reduction of transcripts from the hemizygous region may increase the availability of specific microRNAs, which in turn may exert in-trans regulation of target genes outside the deleted region, eventually contributing to the phenotype. Here we prospect a competing endogenous RNA (ceRNA) approach for the identification of candidate genes target of epigenetic regulation in deletion syndromes. As a model, we analyzed the 5q- myelodysplastic syndrome. Genes in haploinsufficiency within the common 5q deleted region in CD34+ blasts were identified in silico. Using the miRWalk 2.0 platform, we predicted microRNAs whose availability, and thus activity, could be enhanced by the deletion, and performed a genomewide analysis of the genes outside the 5q deleted region that could be targeted by the predicted miRNAs. The analysis pointed to two genes with altered expression in 5q- transcriptome, which have never been related with 5q- before. The prospected approach allows investigating the global transcriptional effect of genomic deletions, possibly prompting discovery of unsuspected contributors in the deletion-associated phenotype. Moreover, it may help in functionally characterizing previously reported unexpected interactions. PMID- 26682280 TI - New alternative splicing BCR/ABL-OOF shows an oncogenic role by lack of inhibition of BCR GTPase activity and an increased of persistence of Rac activation in chronic myeloid leukemia. AB - In Chronic Myeloid Leukemia 80% of patients present alternative splice variants involving BCR exons 1, 13 or 14 and ABL exon 4, with a consequent impairment in the reading frame of the ABL gene. Therefore BCR/ABL fusion proteins (BCR/ABL OOF) are characterized by an in-frame BCR portion followed by an amino acids sequence arising from the out of frame (OOF) reading of the ABL gene. The product of this new transcript contains the characteristic BCR domains while lacking the COOH-terminal Rho GTPase GAP domain. The present work aims to characterize the protein functionality in terms of cytoskeleton (re-)modelling, adhesion and activation of canonical oncogenic signalling pathways. Here, we show that BCR/ABL OOF has a peculiar endosomal localization which affects EGF receptor activation and turnover. Moreover, we demonstrate that BCR/ABL-OOF expression leads to aberrant cellular adhesion due to the activation of Rac GTPase, increase in cellular proliferation, migration and survival. When overexpressed in a BCR/ABL positive cell line, BCR/ABL-OOF induces hyperactivation of Rac signaling axis offering a therapeutic window for Rac-targeted therapy. Our data support a critical role of BCR/ABL-OOF in leukemogenesis and identify a subset of patients that may benefit from Rac-targeted therapies. PMID- 26682282 TI - Panniculectomy Combined with Bariatric Surgery by Laparotomy: An Analysis of 325 Cases. AB - Surgical treatment of obese patients is much debated in the literature because of the significant intraoperative risks related to comorbidities presented by this type of patients. Recent literature suggests that panniculectomy should follow bariatric surgery after the patient's weight loss has been stabilized. However, when performed by laparotomy, bariatric surgery can be combined with panniculectomy. This paper presents the analysis of 325 cases of patients undergoing abdominal panniculectomy combined with bariatric surgery. The study highlights the risks, complications, and benefits of the combined procedure and describes a standardized technique for excision of a large abdominal panniculus in a short operating time. PMID- 26682281 TI - Natural Killer Cells in Viral Hepatitis. AB - Natural killer (NK) cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in chronic infection. Here, we review the role of NK cells against hepatitis C virus (HCV) and hepatitis B virus (HBV), two agents that cause acute and chronic hepatitis in humans. Interest in NK cells was initially sparked by genetic studies that demonstrated an association between NK cell-related genes and the outcome of HCV infection. Viral hepatitis also provides a model to study the NK cell response to both endogenous and exogenous type I interferon (IFN). Levels of IFN-stimulated genes increase in both acute and chronic HCV infection and pegylated IFNalpha has been the mainstay of HCV and HBV treatment for decades. In chronic viral hepatitis, NK cells display decreased production of antiviral cytokines. This phenotype is found in both HCV and HBV infection but is induced by different mechanisms. Potent antivirals now provide the opportunity to study the reversibility of the suppressed cytokine production of NK cells in comparison with the antigen-induced defect in IFNgamma and tumor necrosis factor-alpha production of virus-specific T cells. This has implications for immune reconstitution in other conditions of chronic inflammation and immune exhaustion, such as human immunodeficiency virus infection and cancer. PMID- 26682284 TI - Leading innovation. PMID- 26682283 TI - An alternative to domain-general or domain-specific frameworks for theorizing about human evolution and ontogenesis. AB - This paper maintains that neither a domain-general nor a domain-specific framework is appropriate for furthering our understanding of human evolution and ontogenesis. Rather, as we learn increasingly more about the dynamics of gene environment interaction and gene expression, theorists should consider a third alternative: a domain-relevant approach, which argues that the infant brain comes equipped with biases that are relevant to, but not initially specific to, processing different kinds of input. The hypothesis developed here is that domain specific core knowledge/specialized functions do not constitute the start state; rather, functional specialization emerges progressively through neuronal competition over developmental time. Thus, the existence of category-specific deficits in brain-damaged adults cannot be used to bolster claims that category specific or domain-specific modules underpin early development, because neural specificity in the adult brain is likely to have been the emergent property over time of a developing, self-structuring system in interaction with the environment. PMID- 26682285 TI - What's eating you? ant-induced alopecia (pheidole). AB - Ant-induced alopecia is a rare cause of acute, localized, nonscarring hair loss. It is most commonly caused by Pheidole pallidula ants, which can be found worldwide but are most common in Iran. The resulting alopecia can have many morphologic patterns (eg, patch, linear, nondiscrete) and thus ant-induced alopecia should be considered in the differential diagnosis for patients from endemic areas who present with new-onset localized hair loss. The condition is self-limited; however, patients should be evaluated for other more common causes of alopecia, especially in the absence of a convincing history. PMID- 26682286 TI - Status report from the American Acne & Rosacea Society on medical management of acne in adult women, part 1: overview, clinical characteristics, and laboratory evaluation. AB - Acne presenting in adult women is commonly encountered in clinical practice. Many affected women have had acne during their teenaged years, have tried several therapies in the past, and are seeking effective treatment. Others are frustrated by the inexplicable emergence of acne as an adult when they never had it as a teenager. Both groups seek an explanation of why they have acne, are often psychosocially affected by its effects on appearance and self-esteem, and all are wanting effective and safe treatment. Clinicians are encouraged to connect favorably with each patient through careful history and physical examination and to consider underlying causes of androgen excess. Practical approaches to examination and laboratory evaluation are discussed. PMID- 26682287 TI - Bullous Henoch-Schonlein purpura in children. AB - Henoch-Schonlein purpura (HSP) is a systemic vasculitis that is common in the pediatric population and often presents with the classical triad of palpable purpura, arthralgia, and abdominal pain. We describe a case of HSP in a 14-year old adolescent girl who presented with atypical features of painful hemorrhagic bullae. The patient was treated with high-dose steroids, dapsone, and supportive therapy with remarkable improvement. PMID- 26682288 TI - A novel method of skin closure for aging or fragile skin. AB - A novel method of skin closure is detailed for surgical removal of tumors in patients with aging or thin and fragile skin. A polyethylene film with an acrylate adhesive was used as an adjunct to the dermis to help provide stability for suturing. Cases are presented with clinical photographs to demonstrate how this technique may prevent wound complications in elderly patients or those with fragile skin. PMID- 26682289 TI - Tolerance of fragranced and fragrance-free facial cleansers in adults with clinically sensitive skin. AB - Although mild, fragrance-free, nonfoaming cleansers generally are recommended for individuals with sensitive skin, many consumers choose fragranced foaming cleansers. The addition of hydrophobically modified polymers (HMPs) to mild facial cleansers has been shown to improve product tolerability in individuals with sensitive skin while facilitating foaming. The objective of the 2 studies reported here was to assess the tolerability of a mild, HMP-containing, foaming facial cleanser with a fragrance that was free of common allergens and irritating essential oils in patients with sensitive skin. In the first study, 8 participants with clinically diagnosed fragrance sensitivity used a gentle foaming HMP-containing facial cleanser with or without fragrance for 3 weeks. Both cleansers improved global disease severity, irritation, and erythema with similar cleansing effectiveness. The second study was a 3-week, prospective, double-blind, randomized, 2-center study of 153 participants with clinically diagnosed sensitive skin. In this study, the fragranced gentle foaming cleanser with HMP was as well tolerated as a benchmark gentle, fragrance-free, nonfoaming cleanser. Itching, irritation, and desquamation were most improved from baseline in both groups. The participant-rated effectiveness of the cleanser with HMP was similar or better than the benchmark cleanser after 3 weeks of use. In conclusion, the gentle facial cleanser with HMPs and a fragrance offers a new option for adults with sensitive skin who may prefer, and commonly use, a fragranced and foaming product. PMID- 26682290 TI - Imiquimod cream 2.5% and 3.75% applied once daily to treat external genital warts in men. AB - We assess the safety and efficacy of imiquimod cream 3.75% and 2.5% in men with external genital warts (EGWs). Two multicenter, randomized, double-blind, placebo controlled studies were conducted in a total of 447 (225 from study 1 and 222 from study 2) male patients (aged >=12 years) with 2 to 30 EGWs and a total wart area of 150 mm2 or greater. Participants were randomized (2:2:1) to imiquimod cream 3.75% or 2.5% or placebo applied once daily until complete clearance or a maximum of 8 weeks (end of treatment [EOT]). There was an 8-week follow-up period (end of study [EOS]) for participants who did not achieve complete clearance by EOT. Participants who achieved complete clearance were observed for an additional 12 weeks. The primary efficacy end point was complete clearance rate. Safety assessments included visual assessment of local skin reactions, number and duration of required rest periods, adverse events (AEs), and clinical laboratory tests. Study results indicated that new imiquimod formulations are beneficial in treating EGWs in men. PMID- 26682291 TI - What is your diagnosis? Fixed cutaneous sporotrichosis. PMID- 26682292 TI - Chromoblastomycosis. PMID- 26682293 TI - Occupational contact dermatitis from carbapenems. PMID- 26682295 TI - Solitary lesion on the left ankle. PMID- 26682294 TI - Nevus of Ota/oculodermal melancytosis: a rare report of an oral mucosal lesion involving the hard palate. PMID- 26682296 TI - Resident involvement in policy-making. AB - Politics greatly affect how physicians practice medicine. As dermatology residents, it is vital that we familiarize ourselves with the role of the American Academy of Dermatology Association in policy-making as well as opportunities for residents to help shape the future of our specialty. PMID- 26682297 TI - Acute generalized exanthematous pustulosis associated with ranolazine. AB - Acute generalized exanthematous pustulosis (AGEP) is a potentially widespread, pustular, cutaneous eruption commonly associated with drug administration. We report a case of AGEP associated with the antianginal, anti-ischemic agent ranolazine. The patient, an 83-year-old man, had a validation score of 10 out of 12 in accordance with the EuroSCAR criteria (8-12 is considered definitive), although it may have been higher had blood work been performed prior to diagnosis and treatment. After ranolazine was discontinued and a course of tapered oral prednisone was prescribed, the rash resolved with subsequent desquamation. PMID- 26682298 TI - Cutaneous leishmaniasis: an emerging infectious disease in travelers. AB - Leishmaniasis describes any of 3 diseases caused by protozoan parasites of the genus Leishmania, the most common of which is cutaneous leishmaniasis. The majority of cutaneous cases occur in Central and South America, the Mediterranean basin, the Middle East, and Central Asia. Most cases diagnosed among nonmilitary personnel in the United States are acquired in Mexico and Central America. Here, we present the case of an American tourist who developed localized cutaneous leishmaniasis 2 weeks after returning from Costa Rica. After undergoing several unsuccessful rounds of empiric antibiotic treatment for a presumed Staphylococcus aureus skin infection, the patient was referred to our dermatology clinic where cutaneous leishmaniasis was diagnosed by tissue biopsy. This case highlights the importance of cutaneous leishmaniasis as an emerging infectious disease that may be misdiagnosed due to its rarity and varied clinical presentation as well as the limited use of tissue biopsy in general practice. We also provide relevant background information on cutaneous leishmaniasis, a rhyming poem, and an illustration in order to promote greater awareness of this disease and assist clinicians with its diagnosis. PMID- 26682299 TI - Erythematous scaly patch on the jawline. PMID- 26682300 TI - Staphylococcal scalded skin syndrome in pregnancy. PMID- 26682336 TI - Additional thoughts on the new treatment Kybella. AB - With the recent approval of Kythera Biopharmaceuticals (Westlake Village, California) submental fat injectable treatment Kybella, there comes a lot of excitement-but, also a bit of concern. The idea of having a nonsurgical, nonliposuction treatment for people who have a double chin is certainly exciting. The hope has been that this new treatment will provide opportunities for the many people out there who are focused on the appearance of their submental fullness to have access to a safe. affordable, and reliable treatment.With the approval of this product. there are several misconceptions that the authors herein discuss. PMID- 26682337 TI - Cellfina observations: pearls and pitfalls. AB - In our experience, patients tend to consider any undesirable feature on their body from the knees to the umbilicus, and even the arms, to be cellulite. It is important to educate prospective patients that Cellfina (Uithera, Inc, Mesa, Arizona) most effectively treats dimple-type cellulite, whereby fibrous bands inserting into the undersurface of the skin cause a puckered appearance. In this brief communication, we would like to share our experience in optimizing outcomes with Cellfina for the treatment of cellulite. PMID- 26682338 TI - Introduction. PMID- 26682339 TI - Introduction. PMID- 26682340 TI - Mentorship: Stewards of China's future. PMID- 26682342 TI - Case study. "Lethal" fetal anomalies and elective cesarean. Commentary. PMID- 26682343 TI - Case study. "Lethal" fetal anomalies and elective cesarean. Commentary. PMID- 26682344 TI - John Michael Kilby, MD. PMID- 26682345 TI - Translational research: role for the clinical laboratory professional? PMID- 26682346 TI - New challenges are "brewing" for the regulation of opiates. PMID- 26682347 TI - The rise of e-cigarettes: implications for health promotion. PMID- 26682348 TI - 5 Communication Strategies for Healthcare Workers. PMID- 26682349 TI - Diabetic women face higher CV risks than men. PMID- 26682350 TI - Half of US adults have diabetes, prediabetes. PMID- 26682351 TI - Northwest Kidney Centers honors Bill Peckham. PMID- 26682352 TI - AKF gala recognizes caregivers, patients. PMID- 26682353 TI - Electrical Contacts to Nanomaterials. AB - The efficient passage of electrical current from an external contact to a nanomaterial is necessary for harnessing characteristics unique to the nanoscale, such as those relevant to energy quantization. However, an intrinsic resistance pertinent to dimensionality crossover and the presence of impurities precludes optimal electrical contact formation. In this review, we first discuss the relevant principles and contact resistance measurement methodologies, with modifications necessary for the nanoscale. Aspects related to the deposition of the contact material are deemed to be crucial. Consequently, the use of focused ion beam (FIB) based deposition, which relies on the ion-induced decomposition of a metallorganic precursor, and which has been frequently utilized for nanoscale contacts is considered in detail. PMID- 26682354 TI - Utilization of Microcapsule Technology in Foods. AB - Microencapsulation technology has greatly accelerated the development of food industry and has a bright future for further applications. In this review paper, we introduce the current researches, latest advances and trends of core materials, wall materials, microencapsulation technology, as well as the encapsulation of food additives, bioactive substance, esculent oils, probiotics and other substances, and their application in food industry. PMID- 26682355 TI - Rapid and One-Pot Synthesis of Self-Assembled CdSe Quantum Dots Functionalized with beta-Cyclodextrin: Reduced Cytotoxicity and Band Gap Engineering. AB - We report a simple, rapid and one step method for the synthesis and in situ functionalization of CdSe quantum dots (QDs) with beta-cyclodextrin (beta-CD) in aqueous solution via electron beam (EB) irradiation technique. A probable mechanism has been elucidated for the formation of the QDs using pulse radiolysis technique. The average size of the QDs was found to be in the range of 2-3 nm with a size distribution of -14%. XPS measurements indicate that the -OH groups of the beta-CD molecules binds predominantly with the Cd atoms present on the surface of the QDs. These QDs displayed broad photoluminescence (PL) with two emission peaks at 525 nm and 600 nm, which could be tuned by varying the experimental parameters. The broad PL spectrum has been attributed to the polydispersity in the density and the distribution of trap/defects states. Time resolved PL decay measurements further substantiated the domination of surface state originated carrier relaxation processes in the overall PL decay dynamics of QDs synthesized at higher doses and dose rates. The present study reveals that beta-CD passivate the QDs by a non-inclusion complex, induces the self-assembling process into a networking architecture and simultaneously reduces their cytotoxicity as compared to the bare nanoparticles. The methodology described in this article may provide unique and interesting aspects to regulate and fine tune the formation of superstructures of nanomaterials vis-a-vis their optoelectronic properties. PMID- 26682356 TI - Recyclable Mesoporous Ceria Supported Gold Nanoparticles Based Catalyst for O Arylation of Phenols. AB - Ceria supported gold nanoparticles (Au-CeO2 NPs) were prepared by a simple deposition-precipitation method. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and Raman analysis indicated the formation of gold nanoparticles over phase pure cerianite ceria support. The presence of gold nanoparticles was well identified by UV-DRS study. In addition, the field emission scanning electron microscope (FESEM) and high resolution transmission electron microscope (HR-TEM) images revealed that the maximum number of particles having spherical shape were approximately 10 nm size. Subsequently, surface area of the catalyst determined from BET, Langmuir and DFT methods were found to be 83.1, 134 and 85.2 m2 g(-1) respectively. N2 absorption-desorption measurement revealed that Au-CeO2 NPs was mesoporous in nature. Au-CeO2 NPs proved to be an efficient catalyst for the O-arylation reactions. The reaction conditions were optimized using 2,6-dimethoxyphenol and 1-chloro-4-nitrobenzene as a model substrate by changing the solvent, base, quantity of catalyst, and temperature. The scope of the work was extended to various substituted phenols and aryl halides (F, Cl and Br) and reusability of catalyst was tested for four cycles which showed no loss in its activity. PMID- 26682357 TI - Shape-Selective Catalysis in the Alkylation of Naphthalene: Steric Interaction with the Nanospace of Zeolites. AB - Steric interaction of reagents with nanospace of zeolites was studied in alkylation: isopropylation, sec-butylation, and tert-butylation of naphthalene (NP) over several large-pore zeolites to elucidate the mechanism of shape selective catalysis. Selectivities for beta,beta- and 2,6-dialkylnaphthalene (DAN) were influenced by the type of zeolite and bulkiness of alkylating agent. Shape-selective formation of beta,beta- and 2,6-diisopropylnaphthalene (DIPN) occurred only over H-mordenite (MOR) in the isopropylation of NP. Bulky alpha,alpha- and alpha,beta-DIPN are excluded because of steric restriction at their transition states by the MOR channels, resulting in the selective formation of beta,beta- and 2,6-DIPN. AFI (SSZ-24) gave also high selectivities for 2,6 DIPN, and CFI (CIT-5) and MSE (MCM-68) gave high selectivities for beta,beta DIPN. The lower selectivities for 2,6-DIPN were observed over the zeolites, ATS (SSZ-55), LFR (SSZ-42), DON (UTD-1), SFH (SSZ-53), FAU (Y-zeolite), BEA (zeolite beta), and CON (CIT-1). Their channels allow the accommodation of bulky isomers, resulting in the catalysis under kinetic and/or thermodynamic controls. The selectivities for beta,beta- and 2,6-DAN were enhanced with the increase in bulkiness of alkylating agents: 1-butene for sec-butylation and 2-methylpropene for tert-butylation, even over zeolites with large pores and channels: the transition states of the least bulky isomers only fit the channels, and the other bulky isomers are excluded by steric restriction of the channels. However, tert butylation over FAU, BEA, and CON had selectivities of around 50-60% for 2,6 DTBN, and almost 100% selectivities for beta,beta-DTBN. These zeolites cannot recognize the differences between 2,6- and 2,7-DTBN, but they can differentiate beta,beta-DTBN from the other isomers. The results indicate that the fitting of the least bulky isomers to zeolite channels, resulting in the exclusion of other bulky isomers, is a key for highly shape-selective catalysis. PMID- 26682358 TI - Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-MPA and CdTe-MSA Quantum Dots. AB - CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining. PMID- 26682359 TI - Cobalt Dithiocarbamate Coordination Polymeric Nanoparticles: Morphology Dependent Magnetic and Antimicrobial Properties. AB - Various synthetic methods were employed on a single precursor to synthesize magnetic cobalt dithiocarbamate (Co(dtc-SB)) coordination polymer nanoparticles (MCP NPs) having different morphologies. When subjected to hydrothermal method, the precursor led to the formation of nanosheets (NSs) of MCP (100 x 80 nm), whereas the same precursor when set to slow diffusion precipitation, formed nanowires (NWs) with 30 nm diameter. Further, on micro-emulsion ultrasonication, uniform MCP nanocubes (NCs) -5 nm were obtained. MCP NPs are weakly ferromagnetic in nature with a narrow hysteresis loop opening. In addition, the magnetic properties of MCP NPs are shown to be highly dependent on size. Further, the antimicrobial activity of MCP NPs against various microbes was also shown to be highly size dependent. The biocompatible MCP NCs were found to have the lowest minimum inhibitory concentration (MIC) value of 6.25 MUg/ml against S. aureus and K. pneumoneae, which demonstrate that NPs are equally effective against both gram positive and gram negative bacteria. PMID- 26682360 TI - Synthesis and Photoluminescence Characteristics of Eu(3+)-Doped Molybdates Nanocrystals. AB - In this paper, the Eu(3+)-doped molybdate (CaMoO4, ZnMoO4 and BaMoO4) phosphors have been prepared by a hydrothermal method through modulating the pH value of the precursor solution (pH = 8, 10, and 12, respectively). The crystalline phase, morphology, photoluminescent properties of the prepared samples were systematically characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and photoluminescence (PL) spectra. The results indicate that the photoluminescence and morphology can be affected by the precursor solution. And the growth of the ZnMoO4 crystals also can be affected by the pH value of the precursor solution. PMID- 26682361 TI - Two Dimensional Optoelectronic Simulation Based Comparison of Top and Bottom Contact Organic Phototransistors. AB - This paper deals with two-dimensional optoelectronic simulation based study of organic phototransistors. The top and bottom contact device structures were simulated to compare their characteristics under dark and under light illumination conditions. It was observed that the performance of these phototransistors can be tuned by shining a monochromatic light of given intensity. Further, the photosensitivity of the top and bottom contact phototransistors was compared and it was concluded that the difference in their photocurrent can be attributed to their different carrier extraction areas, which also leads to the difference in their contact resistances. Our results clearly indicate that the top contact structure has higher photosensitivity compared to the bottom contact structure. Furthermore, we simulated the dependence of photosensitivity on gate voltage, light intensity and channel length of the two structures and found the presence of both photoconductive and photovoltaic effects governing performance of organic phototransistors. Finally by simply scaling the device channel length contact resistance in the bottom and top contact organic photo transistors were estimated under different light illumination conditions. PMID- 26682362 TI - Tweaking Electrical and Dielectric Properties of Nickel Oxide Nanocrystals by Varying the Surfactant. AB - The influence of cationic cetyltrimethylammonium bromide (CTAB) and neutral polymeric polyvinylpyrrolidone (PVP) surfactants on electrical and dielectric properties of NiO nanocrystals is investigated. It is demonstrated that, compressive strain of nanocrystals is higher with PVP than that of CTAB. Consequently surfactant type has significant influence on intrinsic defects of nanocrystals. This is attributed to the difference in stabilization of metallic ions against agglomeration that leads to variation in rate of hydrolysis. Particularly, in the case of PVP assisted synthesis, higher stabilization leads to slow nucleation rate with lower defect density. As a result the hopping time of charge carriers decreases which in turn enhances the conductivity of nanocrystals as evidenced from the shifting of dielectric loss peak to higher frequency. PMID- 26682363 TI - Electrodeposition of Nanocrystalline Chromium Coatings Based on 1-Butyl-3 Methylimidazolium-Bromide Ionic Liquid. AB - The electrochemical behavior of trivalent chromium reduction from 1-butyl-3 methylimidazolium-bromide ([BMIM]Br) ionic liquid is studied. The result of cyclic voltammetry shows that the Cr(III) reduction is irreversible and occurs in two steps, Cr(III)to Cr(II), and Cr(II) to Cr(0), respectively. In the electrochemical impedance spectroscopy measurements, the preferable equivalent circuit is made to fit the experimental data. The effects of electroplating parameters on coating thickness and electrodepositon rate are investigated by potentiostatic method on Cu electrode from Cr(III)-[BMIM]Br solution. The results show that the temperature and depositing potential have great effect on the coating thickness and electrodeposition rate. The surface morphology and composition of deposited Cr are investigated using scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS). SEM analysis shows that chromium electrodeposits obtained on Cu electrodes present a ball-like structure. EDS analysis shows that the coatings are composed of Cr. Moreover, the corrosion resistance of the as-deposited chromium layer is evaluated using polarization curves. The results show that the corrosion resistance of the chromium coatings obtained at higher potential is better. PMID- 26682364 TI - Synthesis and Characterization of Poly(N-isopropylacrylamide)/SBA-15 Silica Nanocomposites. AB - The combination of the mesoporous silica material SBA-1 5 with the temperature responsive hydrogels, such as poly(N-isopropylacrylamide) P(N-iPAAm) can lead to the formation of a material with the potential for application as a new drug delivery system, given that self-regulated delivery allows for drug release when needed. The present work studies the synthesis and characterization of hybrid systems consisting of the poly(N-isopropylacrylamide) hydrogel and SBA-15 by varying the amount of hydrogel within the silica network. A systematic study on the structural properties of hybrid samples, their thermal stability and the degradation of the polymer chains in silica was carried out through characterization techniques, including SAXS, thermogravimetry and physical adsorption of N2. The results were critically examined and compared with pure SBA 15. The present study's results demonstrated that the thermosensibility of P(N iPAAm) was retained in the hybrid system, which presented a low critical solution temperature, similar to that of pure P(N-iPAAm). Moreover, the hydrogel did not fully occupy the available intrachannel space, making the [SBA-15/P(N-iPAAm)] hybrids a very promising candidate for hosting and further delivery, under appropriate conditions, of a variety of molecules of pharmaceutical interest. PMID- 26682365 TI - Impact of Ambient Pressure on Titania Nanoparticle Formation During Spray-Flame Synthesis. AB - Nanocrystalline titania was synthesized via liquid-fed spray-flame synthesis in a hermetically closed system at various pressures. Titanium tetraisopropoxide dissolved in isopropanol was used as precursor. The size, crystal structure, degree of agglomeration, morphology and the band gap of the as-prepared particles were investigated ex situ by nitrogen adsorption, transmission electron microscopy, X-ray diffraction, and UV-VIS absorption spectroscopy. In comparison to synthesis at atmospheric pressure it was found that decreasing pressure has a significant influence on the particle size distribution leading to smaller particles with reduced geometric standard deviation while particle morphology and crystal structure are not affected. Computational fluid dynamics simulations support the experimental findings also indicating a significant decrease in particle size at reduced pressure. Although it is well known that decreasing pressure leads to smaller particle sizes, it is (to our knowledge) the first time that this relation was investigated for spray-flame synthesis. PMID- 26682366 TI - Size-Dependent Surface Energy Density of Spherical Face-Centered-Cubic Metallic Nanoparticles. AB - The surface energy density of nano-sized elements exhibits a significantly size dependent behavior. Spherical nanoparticle, as an important element in nano devices and nano-composites, has attracted many interesting studies on size effect, most of which are molecular dynamics (MD) simulations. However, the existing MD calculations yield two opposite size-dependent trends of surface energy density of nanoparticles. In order to clarify such a real underlying problem, atomistic calculations are carried out in the present paper for various spherical face-centered-cubic (fcc) metallic nanoparticles. Both the embedded atom method (EAM) potential and the modified embedded atom method (MEAM) one are adopted. It is found that the size-dependent trend of surface energy density of nanoparticles is not governed by the chosen potential function or variation trend of surface energy, but by the defined radius of spherical nanoparticles in MD models. The finding in the present paper should be helpful for further theoretical studies on surface/interface effect of nanoparticles and nanoparticle reinforced composites. PMID- 26682367 TI - Diosgenin Functionalized Iron Oxide Nanoparticles as Novel Nanomaterial Against Breast Cancer. AB - Iron oxide nanoparticles (IONPs) have gained immense importance recently as drug nanocarriers due to easy multifunctionalization, simultaneous targeting, imaging and cancer hyperthermia. Herein, we report a novel nanomedicine comprising of IONPs core functionalized with a potent anticancer bioactive principle, diosgenin from medicinal plant Dioscorea bulbifera via citric acid linker molecule. IONPs were synthesized by reverse co-precipitation and characterized using field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). Diosgenin functionalization was confirmed using fourier transform infrared spectroscopy (FTIR) and biochemical methods. Synthesized IONPs, citrate linked IONPs (IONPs CA), diosgenin functionalized IONPs (IONPs-D) along with free citric acid and diosgenin were checked for anticancer activity against MCF7 breast cancer cells by MTT assay, wound migration assay, confocal microscopy and protein expression by western blotting. Size of IONPs, IONPs-CA and IONPs-D gradually increased ranging from 12 to 21 nm as confirmed by FESEM and HRTEM. Signature peaks of diosgenin at 2914, 1166 and 1444 cm-1 IONPs-D, revealed in FTIR indicated the presence of functionalized diosgenin. IONPs-D exhibited 51.08 +/- 0.37% antiproliferative activity against MCF7 cells, which was found to be superior to free citric acid (17.71 +/- 0.58%) and diosgenin (33.31 +/- 0.37%). Treatment with IONPs-D exhibited reduced wound migration upto 40.83 +/- 2.91% compared to bare IONPs (89.03 +/- 2.58%) and IONPs-CA (50.35 +/- 0.48%). IONPs-D and diosgenin exhibited apoptosis induction, confirmed by Alexa Fluor 488 annexin V/PI double-stained cells indicating extensive cell membrane damage coupled with PI influx leading to nuclear staining in treated cells. IONPs-D mediated selective PARP cleavage strongly rationalized it as superior apoptotic inducers. Based on these findings, IONPs-D can be considered as first diosgenin functionalized novel magnetic nanomedicine with antiproliferative, migration inhibiting and apoptosis inducing properties against breast cancer. PMID- 26682368 TI - Synthesis and Characterization of Bimetallic Ni50Pt50 Catalyst Supported on SiO2 for N2O Decomposition. AB - Nanometallic and bimetallic catalyst of Ni, Pt and Ni50Pt50 were studied by the decompositions of N2O. The catalyst were prepared by incipient wetness impregnation of the silica with low superficial area of 50 m2/g supported with aqueous solution of the metal precursors, for Pt H2Pt Cl6 x 6H2O was used and for Ni, Ni(NO3)2 was used to a total metal loading of 1% wt. Catalyst were oxidized for 2 hours at 400 degrees C with O2, then the samples were reduced for 30 minutes with N2 and 2 hours with H2, all at the same temperature. The catalyst was characterized by Transmission Electron Microscopy (TEM), High Angular Annular Dark Field (HAADF), High Resolution Transmission Electron Microscopy (HR-TEM) and Termoprogramed Reduction (TPR). The mean particle sizes obtained by TEM and HAADF were about 12.5 nm for Ni/SiO2, 2.8 nm for Pt/SiO2 and 3.5 nm Ni50Pt50/SiO2 catalysts respectability. HR-TEM and HAADF analysis showed differences between Ni and Pt catalysts displaying mainly cuboctahedral shapes. Stepped surface defects were found in the Ni50Pt50/SiO2 catalyst. Finally Ni50Pt50/SiO2 was more active than Pt/SiO2 and Ni/SiO2 catalysts for the decomposition of N2O. PMID- 26682369 TI - Association of Yeast Alcohol Dehydrogenase with Superparamagnetic Nanoparticles: Improving the Enzyme Stability and Performance. AB - Alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae was covalently attached, via glutaraldehyde, to magnetite nanoparticles (MagNP) previously coated with aminopropyltriethoxysilane (MagNP/APTS), or with a silica shell followed by the APTS coating (MagNP@SiO2/APTS). In both cases, a great improvement of enzymatic activity has been observed for the ethanol-acetaldehyde conversion. The MagNP@SiO2/APTS-ADH system exhibited the best stability with respect to pH and temperature. Its residual activity after 10 successive recovery cycles and 24 h storage, was maintained around 80% in comparison with 20% for the MagNP/APTS system, and a null activity for free ADH. Luminescence measurements for the immobilized enzyme indicated the occurrence of conformational changes on ADH, contributing for its improved catalytic performance. PMID- 26682370 TI - Compound Method to Disperse CaCO3 Nanoparticles to Nano-Size in Water. AB - The invalidation of CaCO3 nanoparticles (nCaCO3) is often caused by the fact of agglomeration and inhomogeneous dispersion which limits its application into water-based drilling muds for low permeability reservoirs such as coalbed methane reservoir and shale gas/oil reservoir. Effective methods to disperse nCaCO3 to nano-size (<= 100 nm) in water have seldom been reported. Here we developed a compound method containing mechanical stirring, ultrasonic treatment, the use of surfactant and stabilizer to disperse nCaCO3 in water. It comprises the steps adding 2% nCaCO3, 1% sodium dodecyl sulfonate (SDS), 2% cetyltrimethyl ammonium bromide (CTAB), 2% OP-10, 3% to 4% biopolymer (XC) in water successively, stirring it at a shear rate of 6000 to 8000 r/min for 15 minutes and treating it with ultrasonic at a frequency of 28 KHz for 30 to 40 minutes. The dispersed nCaCO3 was characterized with scanning electron microscope (SEM), transmission electron microscope (TEM) and particle size distribution (PSD) tests. We found that nCaCO3 could be dispersed to below 100 nm in water and the medium value of nCaCO3 was below 50 nm. This method paved the way for the utilization of nCaCO3 in drilling fluid and completion fluid for low permeability reservoirs such as coal seams and shale gas/oil formations. PMID- 26682371 TI - Synthesis of BaFe12O19 Materials by Mechano-Thermal Route: Novel Inorganic Pigment with High Near-Infrared Reflectance. AB - We have prepared BaFe12O19 materials by annealing the ball milled reaction mixture at 1000 degrees C and studied by various characterization techniques. Among the several annealed samples, the samples prepared from 2-5 h ball milled powder show (nearly) single phase of BaFe12O19 materials with reduced average particle size of -42 nm, whereas the reaction mixture ball milled for longer duration (>=10 h) yielded contaminated BaFe12O19 phase. The platelet hexagonal shape grain is seen in the high resolution scanning electron microscope (HRSEM) micrographs for the BaFe12O19 materials. The HRSEM images indicate sizes of grains are in the range of 418 nm to 2.58 MUm in hexagonal basal plane and a range of 1 to 2.5 Am in direction of hexagonal axis. The highlight of the work is the present BaFe1201, materials may be used as novel inorganic pigment due to high near infrared (NIR) reflectance. PMID- 26682372 TI - Direct and Efficient Preparation of Graphene Transparent Conductive Films on Flexible Poly Carbonate Substrate by Spray-Coating. AB - Owing to the hydrophobic property and heat-labile of flexible substances, it is difficult to prepare graphene transparent conductive films (TCFs) on flexible substrate in a direct and effective way. Here we prepared a good dispersion of water/graphene oxide (GO)/ethanol, and the fabrication of graphene TCFs on flexible poly carbonate (PC) substrate was made by spray deposition of water/GO/ethanol, followed by the reduction of hydriodic acid (HI) fuming method. It can be found that when ethanol was added to GO solution, the drying dynamics of the spraying solvent increased and the problem of wetting property of GO dispersion on the PC could be effectively resolved. HI acid vapour can achieve an effective reduction of the GO film. The reduction effect of HI acid fuming method is more effective in comparation with traditional HI acid immersed method. An increase in spraying concentration can lead to a rise in coverage degree of film and folding degree of surface. 1/500 mg/ml is a relatively appropriate concentration for spray-coating. The thickness of the film was controlled by adjusting the spraying volume of water/GO/ethanol dispersion. The graphene TCFs exhibit a sheet resistance of less than 15.3 kOmega/sq at 74% transmittance. PMID- 26682373 TI - Design and Development of Allyl Terminal Triaryl Pyridine Core Skeletal Modified Benzoxazines Based Polybenzoxazine-Silica (PBZ-SiO2) Hybrid Nanocomposites. AB - A series of skeletal modified novel allyl terminal benzoxazines (BZ-als) have been successfully designed and developed using triaryl pyridine core diamines via conventional one-pot Mannich reaction. The polybenzoxazine-silica (PBZ-SiO2) nanocomposites were prepared by thermal ring-opening polymerization of benzoxazines with different weight percentages of 3 methacryloxypropyltrimethoxysilane through in-situ sol-gel method. The formation of hybrid nanocomposites was confirmed by FT-IR. The substantial enhancement in the glass transition temperature was remarked for PBZ-SiO2 hybrids than their respective neat PBZ systems. The dielectric constant of the nanocomposites was found decreased with an increment in the silica content. The shift in the characteristic absorption/emissions corresponding to the neat PBZs toward lower wave-length ascertains the successful formation of PBZ-SiO2 nanocomposites. The discernible phase behaviour observed morphological studies reveals the molecular level dispersion of silica particles over the organic networks. PMID- 26682374 TI - Shape Sensitivity on Toxicity of Gold Nanoplates in Breast Cancer Cells. AB - Gold nanomaterials (Au NMs) have been explored for a wide range of applications in catalysis and medicine. Here we report the shape sensitive toxicity of gold nanoplates (Au nanoplates) in breast cancer cell line, MCF7. Au nanoplates induced a dose- and shape-dependent toxicity to cancer cells. Oxidative stress induced by Au nanoplates is believed to be the trigger for the DNA, which resulted in cell apoptosis. In summary, the results from our study demonstrate that morphology appears to play a significant role in mediating the cellular responses and Au triangles nanoplates showed the highest toxicity to the cells. Such findings may be able to shine more light on the shape-dependent interaction between Au NMs and living organisms. PMID- 26682375 TI - The Experimental Study of the Performance of Nano-Thin Polyelectrolyte Shell for Dental Pulp Stem Cells Immobilization. AB - Carious is the most frequent disease of mineralized dental tissues which might result in dental pulp inflammation and mortality. In such cases an endodontic treatment is the only option to prolong tooth functioning in the oral cavity; however, in the cases of severe pulpitis, especially when complicated with periodontal tissue inflammation, the endodontic treatment might not be enough to protect against tooth loss. Thus, keeping the dental pulp viable and/or possibility of the reconstruction of a viable dental pulp complex, appears to become a critical factor for carious and/or pulp inflammation treatment. The nowadays technologies, which allow handling dental pulp stem cells (DPSC), seem to bring us closer to the usage of dental stem cells for tooth tissues reconstruction. Thus, DPSC immobilized within nano-thin polymeric shells, allowing for a diffusion of produced factors and separation from bacteria, may be considered as a cover system supporting technology of dental pulp reconstruction. The DPSC were immobilized using a layer-by-layer technique within nano-thin polymeric shells constructed and modified by nanostructure involvement to ensure the layers stability and integrity as well as separation from bacterial cells. The cytotoxity of the material used for membrane production was assessed on the model of adherent cells. The performance of DPSC nano-coating was assessed in vitro. Membrane coatings showed no cytotoxicity on the immobilized cells. The presence of coating shell was confirmed with flow cytometry, atomic force microscopy and visualized with fluorescent microscopy. The transfer of immobilized DPSC within the membrane system ensuring cells integrity, viability and protection from bacteria should be considered as an alternative method for dental tissues transportation and regeneration. PMID- 26682376 TI - Preparation of Deep Sea Fish Oil-Based Nanostructured Lipid Carriers with Enhanced Cellular Uptake. AB - Nanostructured lipid carriers (NLC) are a promising pharmaceutical delivery system with mean diameter less than 200 nm which are dispersed in an aqueous phase containing emulsifier(s), to increase the water solubility, stability and bioavailability of oil compounds. Herein we prepared a promising NLC with glyceryl monostearate (GMS) as the solid lipid template and deep sea fish oil as the liquid lipid template using melted-ultrasonic method. Fish oil-NLC had a mean size of 84.7 +/- 2.6 nm and a zeta potential that ranged from -17.87 mV to -32.91 mV. The nanoparticles exhibited good stability for four weeks with a high encapsulation efficiency of 87.5 +/- 5.2%. Afterwards, confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to investigate the contribution of Fish oil-NLC in enhancing fluorescein isothiocyanate (FITC) cellular uptake in comparison with free FITC. The results of this study indicated the possibility of this carrier to overcome the shortcomings of deep sea fish oil and to provide a novel bifunctional carrier with nutritional potential and drug delivery ability. PMID- 26682377 TI - Tailoring the Optoelectronic Properties of Nano-Metal Oxides Using Anthocyanins and Lanthanide. AB - Here we report a simple and effective method in tailoring the optoelectronic properties of semi-conducting metal oxide for suitable device application. Sol gel synthesis was used to synthesize manganese doped TiO2 nanopowder and commercially available TiO2 nanopowder was used as reference material. Thick films of these powder were screen printed on FTO coated glass and annealed at 450 degrees C in ambient air. Separately, 60 MUL of neodymium chloride prepared from neodymium oxide, 60 MUL of ruthenium based commercial dye (N719) and 60 MUL of extracts of calendula orange and dog flower were used as sensitizer to improve the photoconductance properties. Elemental analysis confirmed synthesis of composite material of Mn and TiO2. Morphological observation showed a uniform particles of 25 to 50 nm diameter. Optoelectronic properties were studied by using thick films of these powders as working electrode as a function of wavelength from 430 to 750 nm and the cyclic voltammogram were obtained by scanning potential from -1.5 V to +1.5 V at the illumination intensity of 1000 Wm(-2). Sensitization resulted in additional absorption and functional bands. Oxidation peak current was found decreasing with increasing wavelength. Sensitization with flower extract resulted in increased oxidation current at higher wavelength indicating the improved photoconduction in comparison with N719 and neodymium. PMID- 26682378 TI - Evaluation of Nanoparticles Emitted from Printers in a Clean Chamber, a Copy Center and Office Rooms: Health Risks of Indoor Air Quality. AB - Indoor air quality has great impact on the human health. An increasing number of studies have shown that printers could release particulate matters and pose adverse effects on indoor air quality. In this study, a thorough investigation was designed to assess the aerosol printer particle total number concentration (TNC) and size distribution in normal office environment, one copy center, and a clean chamber. Particle analyzers, SMPS, OPS, and CPC3007 were used to monitor the total printing process. In normal office environment, 37 laser printers out of all surveyed 55 printers were classified as high particle emitters. Comparing to laser printers, 5 inkjet printers showed no particle emission. Particle emission level in a copy center increased slightly with TNC elevating to about 2 times of the aerosol background. Simulating test in a clean chamber indicated that printer-emitted particles were dominated by particles in nanoscale (diameter of particle, D(p) < 100 nm). These particles in a sealed clean chamber attenuated so slowly that it still held at high level with the concentration of 1.5 x 10(4) particles/cm3 after printing for 2.5 hours. Our present results demonstrate that printers indeed release particulates which keeping at a high concentration level in the indoor environment. Special care should be taken to this kind of widely applied machines and effective controls of particle emission at printing processes are necessary. PMID- 26682379 TI - Green Synthesis of Silver Nanorods and Optimization of Its Therapeutic Cum Toxic Dose. AB - Germinated Fenugreek seeds are relatively rich in flavonoids and polyphenols than dry seeds. Therefore, germinated fenugreek seeds possess better pharmacological activities. We have used an aqueous extract of germinated fenugreek seeds to reduce silver nitrate into nanoscale silver rods. The silver nanorods showed Surface Plasmon peak at 450 nm as revealed from UV visible spectrum. Field Emission Scanning Electron Microscopy images revealed the monodispersity and rod morphology. X ray diffraction spectrum revealed the FCC crystal structure of nanorods. Fourier transform infrared spectroscopy peaks revealed the interaction between the phytochemicals of germinated fenugreek seeds and the silver nanorods. Characterization studies reveal the validation of the proposed green synthesis protocol to produce monodispersed silver nanorods with phytochemical capping. The phytosynthesized silver nanorods exhibited anticancer activity in skin cancer cell line, which may be due to its nanoscale dimension and the surface functionalization. For the first time, we have optimized the therapeutic cum toxic dose of phytostabilized silver nanorods using skin cancer cell model. PMID- 26682380 TI - Mass Production of Carbon Nanofibers Using Microwave Technology. AB - Carbon nanotubes (CNFs) were produced by gas phase single stage microwave assisted chemical vapour deposition (MA-CVD) using ferrocene as a catalyst and acetylene (C2H2) and hydrogen (H2) as precursor gases. The effect of the process parameters such as microwave power, radiation time, and gas ratio of C2H2/H2 was investigated. The CNFs were characterized using scanning and transmission electron microscopy (TEM), and by thermogravimetric analysis (TGA). Results reveal that the optimized conditions for CNF production were 1000 W reaction power, 35 min radiation time, and 0.8 gas ratio of C2H2/H2. TEM analyses revealed that the uniformly dispersed CNFs diameters ranging from 115-131 nm. The TGA analysis showed that the purity of CNF produced was 93%. PMID- 26682381 TI - Determination of Phenolic Compounds in Environmental Water by HPLC Combination with On-Line Solid-Phase Extraction Using Molecularly Imprinted Polymers. AB - A novel molecularly imprinted polymer (MIP) was synthesized using halloysite nanotubes (HNT) as matrix, beta-cyclodextrin (beta-CD) and methyl propyl acid (MAA) as functional monomers, and 2,4,6-TCP as template molecule by graft copolymerization. Infrared spectroscopy and transmission electron microscopy (TEM) were used to characterize the as-synthesized imprinted polymer. The selective recognizability of the MIP towards four phenolic analogs were determined and the recognition coefficients for 2,4,6-TCP, 2,6-DCP, 4-CP and phenol were found to be 2.17, 1.85, 2.02 and 1.36, respectively. Using as the packing material of solid-phase extraction, the imprinted polymer has been applied to on-line extraction of the four phenolic compounds in environmental water. The corresponding analytical methods to determine these four phenolic compounds have been developed. Good linear relationships were obtained over the range of 0.05-5.0 mg x L(-1). The average recoveries for spiked samples were in the range of 74.8-97.2%, and the detection limits for 2,4,6-TCP, 2,6-DCP, p chlorophenol, phenol were 0.19, 0.20, 0.75, 0.73 mg x L(-1), respectively. The method is rapid, accurate and high selectivity. It was feasible for the determination of trace level phenolic compounds in environmental samples. PMID- 26682382 TI - Investigating the Properties and Hydrolysis Ability of Poly-Lactic Acid/Chitosan Nanocomposites Using Polycaprolactone. AB - Poly-lactic acid (PLA) has been widely applied in the medical field (in biomedicines such as medical capsules, surgical sutures and suture wounds) owing to its high biodegradability, good biocompatibility and ability to be dissolved in common solvents. Chitosan (CS) is an abundant polysaccharide and a cationic polyelectrolyte present in nature. In this study, the combination of PLA and CS has been used to form PLA/CS nanocomposites having the advantages of both the original components. To enhance the dispersibility and compatibility between PLA and CS in the PLA/CS nanocomposites, polycaprolactone (PCL) is added as a compatibilizer. The Fourier Transform Infrared spectroscopies prove the existence of the interactions of PCL with PLA and CS. A more regular dispersion of CS of 200-400 nm particle size, is observed in the PLA matrix of the PLA/CS nanocomposites containing PCL, through the Field Emission Scanning Electron Microscopy images. The appearance of one glass transition temperature (T(g)) value of PLA/CS/PCL nanocomposites occuring between the T(g) values of PLA and CS in DSC diagrams confirms the improvement in the compatibility between PLA and CS, due to the presence of PCL. The TGA result shows that PCL plays an important role in enhancing the thermal stability of PLA/CS/PCL nanocomposites. The hydrolysis of PLA/CS/PCL nanocomposites in alkaline and phosphate buffer solutions was investigated. The obtained results show that the PLA/CS/PCL nanocomposites have slower hydrolysis ability than the PLA/CS composites. PMID- 26682383 TI - Breast Cancer Tissue Marked Selectively by Magnetic Nanoparticles in an Experimental Animal Model. AB - The use of magnetic nanoparticles have been proposed as alternative techniques to assist breast cancer diagnosis and treatment. Peritumoral and intratumoral biodistribution of magnetic nanoparticles have been the main practical approaches, and the evaluation of breast tumor tissue marked selectively by magnetic nanoparticles has been not widely studied so far. The aim of this study was to evaluate the c-erbB-2 antigen in tissue of a breast cancer animal model as specific target for the use of magnetic nanoparticles coupled to specific Monoclonal Antibody (Mab). A breast cancer animal model was adapted and standardized in female rats. Tumor tissue was characterized histopathological and inmunohistochemical for cancer type and c-erbB-2 expression respectively. A bioconjugate was developed by the covalent union of fluorescent magnetic nanoparticles and anti c-erbB-2 Mab, and was used for incubation in two consecutive slides of breast cancer tissue acoordingly following conditions: (a) the c-erbB-2 receptor previously blocked by a primary antibody, and (b) the c erbB-2 receptor non-blocked. Microscopy fluorescence was used to determine the selective marked of tumor tissue by the bioconjugate. Healthy breast tissue was used as negative control of selective labeling of the bioconjugate. The results show a well-differentiated fluorescent mark by magnetic nanoparticles in the non blocked c-erbB-2 receptor breast cancer tissue condition, the observation suggests the use of the c-erbB-2 antigen as specific target to mark selectively breast tumor tissue by magnetic nanoparticles. PMID- 26682384 TI - Modified MgFe2O4 Ferrimagnetic Nanoparticles to Improve Magnetic and AC Magnetically-Induced Heating Characteristics for Hyperthermia. AB - A ferrimagnetic nanoparticle with a smaller size, a narrower size distribution, and a higher ac heat generation ability has been still studied for intra-arterial or intra-tumoral hyperthermia. In this study, we manipulate the calcining temperature in the range of 400-600 degrees C to modify MgFe2O4 ferrimagnetic nanoparticles (FMNPs) during modified sol-gel process. The modified MgFe2O4 FMNPs have well controlled with small size and narrow size distribution, so that their magnetic and ac magnetically-induced heating characteristics are significantly improved. In particular, MgFe2O4 nanoparticles synthesized at the calcining temperature of 600 degrees C and sintering temperature of 700 degrees C show the most suitable size (58 nm +/- 13 nm) and its distribution (22%) resulting in the highest ac magnetically-induced heating temperature (T(AC,mag), DeltaT = 93 degrees C) and SLP (Specific Loss Power, 600 W/g) at the biologically tolerable range of magnetic field (H(appl) = 140 Oe) and frequency (f(appl) = 110 kHz). It is found to be due to the improvement of magnetic softness and saturation magnetization resulting in the largest hysteresis loss power. All the results in this work clearly demonstrate that calcining process is one of the key parameters to control the proper size and size distribution for improving magnetic and ac magnetically-induced heating characteristics of MgFe2O4 FMNPs, which can be applicable to hyperthermia agents in nanomedicine. PMID- 26682385 TI - Nano-Structured Magnesium Oxide Coated Iron Ore: Its Application to the Remediation of Wastewater Containing Lead. AB - Magnetically separable nano-structured magnesium oxide coated iron ore (IO(MgO)) was prepared using environmentally benign chemicals, such as iron ore (IO), magnesium(II) nitrate hexahydrate [Mg(NO3)2 x 6H2O] and urea; via an easy and fast preparation method. The lO(MgO) was characterized using X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X ray spectroscopy (EDS) and alternating gradient magnetometer (AGM) analyses. The isotherm and kinetic studies indicated that lO(MgO) has a comparably higher Langmuir constant (K(L), 1.69 L mg(-1)) and maximum sorption capacity (33.9 mg g( 1)) for lead (Pb) than other inorganic media. Based on MgO amount, the removal capacity of Pb by IO(MgO) was 2,724 mg Pb (g MgO)(-1), which was higher than that (1,980 mg g(-1)) for flowerlike magnesium oxide nanostructures reported by Cao et al. The kinetics, FE-SEM, elemental mapping and XRD results revealed that the substitution followed by precipitation was identified as the mechanism of Pb removal and plumbophyllite (Pb2Si4O10 x H2O) was the precipitated phase of Pb. A leaching test revealed that IOMgO) had negligible concentrations of leached Fe at pH 4-9. Since the base material, IO, is cheap and easily available, lO(MgO) could be produced in massive amounts and used for remediation of wastewater containing heavy metals, applying simple and fast magnetic separation. PMID- 26682386 TI - Synthesis and Compositional Analysis of Permalloy Powder Prepared by Arc Discharge. AB - We report the synthesis, compositional, structural and magnetic properties of permalloy powders prepared using an arc-discharge method under different atmospheres. Ion beam analysis results showed that powder prepared in air had a higher concentration of oxygen than those prepared under nitrogen or argon atmospheres. X-ray diffraction measurements showed that powders prepared in air contained magnetite (Fe3O4) and other phases, while powders prepared under nitrogen or argon predominately contained permalloy. The permalloy powders contained a broad range of particle sizes, and nanoparticles as small as 10 nm were evident from transmission electron microscopy data. The saturation magnetizations were significantly lower for the powders prepared in air than those prepared under nitrogen or argon. This can be attributed to oxidation, where the saturation magnetization is predominately from Fe3O4 for powders made in air. The coercive fields were also significantly larger for powders prepared in air, which is consistent with the powders containing different phases when compared with the permalloy powders. Our results show that permalloy powders can be made in nitrogen and argon, allowing for the production of low oxygen content permalloy powders for device applications. Our results also suggest that the use of an iron anode could result in Fe3O4 powders. PMID- 26682387 TI - Interaction Studies of Greenly Synthesized Gold Nanoparticles with Bovine Serum Albumin (BSA) Using Fluorescence Spectroscopy. AB - In the present study, gold nanoparticles (AuNPs) with an average particle size of -41.23 nm were synthesized using eco-friendly reducing material (i.e., aqueous Nelumbo nucifera root extract). Rapid reduction results in the formation of polydispersed nanoparticles. The formation of AuNPs was characterized by surface plasmon resonance (SPR) which was determined by UV-Vis spectra (band at 544 nm), FTIR, SEM-EDX, TEM, HR-TEM, and XRD. This study aims to investigate the interaction between AuNPs and Bovine Serum Albumin (BSA) using fluorescence spectroscopy. The analysis of fluorescence spectra and intensity at physiological pH in an aqueous solution indicates that AuNPs have a potent ability to quench the BSA fluorescence by both quenching mechanisms. Resonance light scattering spectra indicated the formation of BSA-AuNPs complex. The number of binding sites and binding constants were determined based on fluorescence quenching at different temperatures. The thermodynamic parameters were also calculated at various temperatures that indicate that hydrophobic forces are abundant in the AuNPs-BSA complex. Negative DeltaG degrees values suggest that the binding process is spontaneous. Synchronous fluorescence spectra showed a blue shift and CD spectra showed an increase in a-helicity content which is an indication of increasing hydrophobicity. PMID- 26682388 TI - Facile Large Scale Production of Few-Layer Graphene Sheets by Shear Exfoliation in Volatile Solvent. AB - Few layer graphene sheets were synthesized from natural graphite through mechanical shear mixer in 1-butanol as solvent. The liquid phase exfoliation of graphite through the shear mixer generated incising forces for 20 minutes which changed the large amount of graphite's flake into few layer graphene. The removal of solvent from the deposited dispersion was performed immediately by keeping at the room temperature. The deposited graphene thin films were characterized by AFM, HR-TEM, XRD, FT-IR and Raman Spectroscopy. The HR-TEM results showed the formation of few layers and well dispersed graphene. The Raman spectroscopy and XRD characterization confirmed the good quality and non-oxidized state of graphene. PMID- 26682389 TI - Double Carbon Nano Coating of LiFePO4 Cathode Material for High Performance of Lithium Ion Batteries. AB - Double carbon-coated LiFePO4 (D-LiFePO4/C) composite with sphere-like structure was synthesized through combination of co-precipitation and solid-state methods. Cetyl-trimethyl-ammonium bromide (CTAB) and citric acid served as two kinds of carbon sources in sequence. SEM images demonstrated that double carbon coating had certain influence on the morphology. The thickness of carbon coating on D LiFePO4/C was about 1.7 nm and the content of carbon was 2.48 wt%, according to HRTEM and TG analysis. The electrochemical impedance spectroscopy analysis indicated that the D-LiFePO4/C composite presented the charge-transfer resistance of 68 Omega and Li ion diffusion coefficient of 2.68 x 10(-13) cm2 S(-1), while the single carbon-coated LiFePO4 (S-LiFePO4/C) exhibited 135.5Omega and 4.03 x 10(-14) cm2 S(-1). Especially, the prepared D-LiFePO4/C electrode showed discharge capacities of 102.9 (10C) and 87.1 (20C) mA h g(-1), respectively, with almost no capacity lost after 400 cycles at 10C, which were much better than those of S-LiFePO4/C composite. PMID- 26682390 TI - Tailoring Energy Bandgap of Al Doped ZnO Thin Films Grown by Vacuum Thermal Evaporation Method. AB - The paper presents the results of our experimental investigation pertaining to tailoring of energy bandgap and other associated characteristics of undoped and Al doped ZnO (AZO) thin film by varying the atomic concentration of Al in ZnO. Thin films of ZnO and ZnO doped with Al (1, 3, and 5 atomic percent (at.%)) were deposited on silicon substrate for structural characterization and on glass substrate for optical characterization. The dependence of structural and optical properties of Al doped ZnO on the atomic concentration of Al added to ZnO has been reported. On the basis of the experimental results an empirical formula has been proposed to calculate the energy bandgap of AZO theoretically in the range of 1 to 5 at.% of Al. The study revealed that AZO films are composed of smaller and larger number of grains as compared to pure ZnO counterpart and density of the grains was found to increase as the Al concentration increased (from 1 to 5 at.%). The transmittance in the visible region was greater than 90% and found to increase with increasing Al concentration up to 5 at.%. The optical bandgap was found to increase initially with increase in atomic concentration of Al concentration up to 3 at.% and decrease thereafter with increasing concentration of Al. PMID- 26682391 TI - A Novel Intelligent Vascular Stent: Preparation and Characterization of Hydrophobic Steel Mesh Stent with Liquid Surface Tension Response. AB - An intelligent vascular stent was fabricated from a hydrophobic mesh tube, which cans in-situ release thrombolytic drugs only by an injection of nitroglycerin solution. The mesh with 80# pore size has the highest hydrophobic property and the most sensitive response performance after 3.00 wt% (Heptadecafluoro-1,1,2,2, tetradecyl)trimethoxysilane (HFTES) treatment. This may be due to the larger hydrophobic effective area and more active fluorine groups of 80# mesh surface treated by 3.00 wt% HFTES. It was proved that the "thrombolytic medicine" could be easily and efficiently into the interior of the stent after triggered only by an injection of nitroglycerin liquid. The in-situ thrombolytic effect and the spent time were satisfactory. The thrombosis had been completely dissolved. This technology provides a potential therapy for vascular restenosis and has great potential applications in the therapy for in-stent restenosis. PMID- 26682392 TI - Nanoporous TiO2-Based Distributed Bragg Reflectors for Near-Infrared Wavelength Applications. AB - We reported the fabrication and characteristics of distributed Bragg reflectors (DBRs), made of titanium dioxide (TiO2) dense/nanoporous film stacks, operating in the near-infrared wavelength region of 0.8-1.1 MUm. To form the nanoporous TiO2 films with a low refractive index (low-n), the oblique angle deposition (OAD) technique was employed at a high incident vapor flux angle of 80 degrees. For the fabricated DBRs consisting of TiO2 dense/nanoporous (high-n/low-n) thin films, the high reflectance band was gradually increased and the stop bandwidth was narrowed with increasing the number of DBR pairs. Particularly, the TiO2 DBR with only 6 pairs exhibited a normalized stop bandwidth (Deltalambda/lambda(c)) of -11.6% at a center wavelength (lambda(c)) of 0.96 MUm as well as high reflectance values of > 95% over a wide mid-infrared wavelength region of 0.9 1.01 MUm (i.e., Deltalambda = 0.111 MUm). Furthermore, the reflectance characteristics were investigated at incident light angles of 20-70 degrees for different polarized lights. For theoretical optical analyses, the reflectance calculations were also performed by a rigorous coupled-wave analysis method, showing a similar tendency to the experimentally measured data. PMID- 26682393 TI - Hydrothermal Synthesis and Upconversion Properties of alpha-NaYF4:Yb3+, Er3+ Nanocrystals Using Citric Acid as Chelating Ligand and NaNO3 as Mineralizer. AB - Yb3+ and Er3+ ions co-doped alpha-NaYF4:Yb3+, Er3+ nanocrystals were successfully synthesized via a facile hydrothermal method using citric acid (CA) as chelating ligand and NaNO3 as mineralizer. The influences of the CA/RE (RE = Y+Yb+ Er) molar ratio, reaction time, reaction temperature and the NaNO3/RE molar ratio on the crystal phases and shapes of as-prepared products have been well investigated. The possible formation mechanism has been discussed in detail and an aggregation growth theory has been proposed. X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), and photoluminescence (PL) spectra were used to characterize the products. Under 980 nm excitation, the emission intensities of the as-prepared nanocrystals were much stronger than that of the nanocrystals modified by ethylenediaminetetraacetic acid (EDTA). Additionally, the as-prepared products maintained spherical shape and high degree of monodispersion, which is expected to be suggestive for the preparation of other complex rare earth fluoride compounds. PMID- 26682394 TI - Nanosheet Graphene Composite Carbon Aerogels from Resorcinol-Formaldehyde via an Adsorption-Assembly Polymerization Method . AB - An adsorption-assembly sol-gel polymerization between graphene oxide (GO) sheets and resorcinol-formaldehyde aqueous solution was investigated as a method to form graphene composite carbon aerogels (GCAs) with cross-linked nanosheet structure and a surface area as high as 489 m2/g. By adjusting the amount of GO and the catalyst of hexamethylenetetramine (HMTA) in the precursor mixture, aerogels with little drying shrinkage under ambient pressure condition could be obtained. Benefiting from the attendance of graphene oxide, the obtained GCAs showed a regular nanosheets structure with countless nano-size particles on the sheet surface, which is quite different from the conventional carbon aerogels. The electrochemical performance of the GCAs were evaluated, they displayed small internal resistance and outstanding electrochemical specific capacitance (131 F/g), as well as a stable cycle performance (no capacitance loss after 5000 cycles). PMID- 26682395 TI - Supercapacitors from Activated Carbon Derived from Granatum. AB - Granatum carbon (GC) as electrode materials for supercapacitors is prepared via the chemical activation with different activating agent such as ZnC2 and KOH with an intention to improve the surface area and their electrochemical performance. The structure and electrochemical properties of GC materials are characterized with N2 adsorption/desorption measurements, scanning electron microscope (SEM), cyclic voltammetry (CV), galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy (EIS). The obtained results show that the specific surface area of the granatum-based activated carbons increased obviously from 573 m2 x g(-1) to 1341 m2 x g(-1) by ZnC2 activation and to 930 m2 x g(-1) by KOH treatment. Furthermore, GCZ also delivers specific capacitance of 195.1 Fx g(-1) at the current density of 0.1 A x g(-1) in 30 wt.% KOH aqueous electrolyte and low capacitance loss of 28.5% when the current density increased by 10 times. PMID- 26682396 TI - Nanosystems in Photoprotection. AB - The ultraviolet (UV) radiation is responsible for stimulating acute responses in the human skin, those including positive responses like vitamin D synthesis along with negative ones such as erythema. The chronic effects of UV radiation include photoaging and cancer. Sunscreens are classified as organic and inorganic and the safety of the products containing them is related to the evaluation of the effects of these actives on the skin (irritation and sensitization) and also the possibility of cutaneous permeation that may cause the product to permeate into the bloodstream, possibly generating systemic toxicity. Nanotechnology plays an important role in overcoming the obstacles related to sunscreens. In this context, there are the nanosystems that have been widely used as vehicles to sunscreens. The use of nanosystems aims to reduce phototoxicity and cutaneous permeation of sunscreens and also to act in improving the photostability, the sun protection factor (SPF) and the protection spectrum of sunscreens. The most studied nanosystems in photoprotection are: liposomes, nanoparticles (lipid, polymeric and inorganic), cyclodextrins and nanoemulsions. PMID- 26682397 TI - Characterization of Field Effect Transistor Biosensors Fabricated Using Layer-by Layer Nanoassembly Process. AB - In order to avoid the fabrication complexity involved with a single carbon nanotube (CNT) based immunosensor, herein we report an FET based biosensor, in which the channel is made out of Carbon Nanotube Thin Film (CNTF). The CNTF channel between the source and drain electrodes is assembled using a combination of photolithography and electrostatic layer-by-layer self-assembly (LbL). The fabricated device behaves like a p-type transistor. The bio-affinity interaction between Protein A and rabbit Immunoglobulin G (IgG) is used to model the immunosensing, and our initial results show the device is capable of detecting IgG concentrations as low as 1 pg/mL. PMID- 26682398 TI - Hydrothermal Synthesis of BiFeO3 Nanoparticles for Visible Light Photocatalytic Applications. AB - Bismuth ferrite is a promising material for visible light response photocatalytic applications due to its narrow band gap. In this work, single crystalline BiFeO3 nanoparticles were prepared by a modified hydrothermal process. The effects of hydrothermal temperature, reaction time and precursor xerogel amoumt on the as prepared BiFeO3 particle size and morphology were investigated by XRD, TEM and HRTEM. The XRD analysis reveals that single crystalline BiFeO3 particles can be obtained when the hydrothermal temperature is kept below 220 degrees C. TEM observation showed that the as-formed BFO particles are in a square or rectangle like shape and that the particle size is increased with increasing hydrothermal temperature. The hydrothermal reaction time and the amount of xerogel could also influence the as-formed BFO particle morphology and size. The band gap of the as prepared BFO nanoparticles was identified by UV-vis diffuse reflectance spectrum. The measurement of photodegradation of methyl orange dye in an aqueous solution revealed that the as-prepared BFO nanoparticles exhibit photocatalytic activity under visible light irradiation. PMID- 26682399 TI - Synthesis and Electrochemical Properties of Nitrogen-Doped Graphene (NG)/Nickle Oxide (NiO) Nanocomposite for Supercapacitor. AB - A novel nitrogen-doped graphene (NG)/nickle oxide (NiO) nanocomposite was synthesized by a facile two-step method, where NiO particles were dispersed on the surface of NG. The NG/NiO nanocomposite is characterized by using field emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Raman spectroscopy. The electrochemical properties of NG/NiO nanocomposite have been studied using cyclic voltammetry (CV), galvanostatic charge/discharge and electrochemical impedance spectroscopy (EIS) techniques. Compared with the nitrogen-doped graphene, the electrode prepared by NG/NiO nanocomposite has a mass specific capacitance of 342 F g(-1) at scan rate of 5 mV s(-1), which is much higher than that of nitrogen-doped graphene (NG). The galvanostatic charge/discharge results show this new kind nanocomposite has high specific capacitance with 320 F g(-1) in the range of 0.1-0.5 V at a current density of 1 A g(-1). The enhanced supercapacitive performance of NG/NiO nanocomposite suggesting its promising potential in supercapacitors. PMID- 26682400 TI - Electrospun Fibrous Nanocomposite Membrane for UV Shielding Applications. AB - In this paper, UV shielding properties of the fibrous composite membranes of PVA and ZnO have been studied and analyzed. Two kinds of approches have been adopted to prepare the fibrous membrane and their corresponding effect on shielding properties have also been systematically studied. It has been observed that the pure PVA fibrous membrane with a wavelength longer than 230 nm could not be filtered which predicted that transparency of the pure PVA samples for both UVA and UVB radiations. In the case of DDM derived composite membrane, UV radiations in the range from 200 to 365 nm have been efficiently absorbed by the sample. The ISM-PVA/ZnO exhibit impressive UV shielding nature which effectively filtered the whole range of UV radiation especially for both UV-B (280-315 nm) and UV-A (315 400 nm). The transmittance results indicate a significant improvement of the UV absorbing property of ISM derived ZnO/PVA. Considering the simplicity of the fabrication of the composite materials, this work might become very useful for commercial exploitation. PMID- 26682401 TI - Rapid Facial Fabrication of Silica Colloidal Crystal Film at the Air/Water Interface. AB - A rapid and facial strategy has been developed to self-assemble 2D or 3D silica colloidal crystals at the air/water interface. The surface hydrophilicity of monodisperse silica microspheres were prepared by the Stober method and modified by physical adsorption of a cationic surfactant (CTAB). The surface-modified silica microspheres were dispersed into an organic solvent and readily self assemble at the air/water interface to form 2D monolayer film. The surface potential (zeta ) of silica microspheres could be changed with different concentration of CTAB aqueous solution. When the surface potential of silica particles was of -36.67 mV, a 2D monolayer film with close-packed and high ordered structure could be easily obtained and may further be transferred onto a solid substrate layer by layer to develop a 3D multilayer film. UV-visible spectrophotometer was used to analyze the orderliness of colloidal crystal film, the Bragg diffraction positions and silica diameters were in good agreement with those were theoretically calculated. In addition, Atomic Force microscopy (AFM) was used to observe the arrangement of colloidal crystals. PMID- 26682402 TI - Thermal Decomposition Fabrication of Fe2O3 Nanoparticle-Sensitized TiO2 Nanotube Arrays and Their Photoelectrochemical Properties. AB - TiO2 nanotube arrays/Fe2O3 nanoparticles (TiO2 NTs/Fe2O3) with enhanced visible light activity were synthesized by a two-step approach including an electrochemical anodization technique followed by a thermal decomposition approach. The structural investigation indicated that Fe2O3 nanoparticles grew uniformly on the walls of TiO2 nanotubes. The Fe2O3 modification of TiO2 NTs resulted in an increase in the visible light adsorption, and the increases in photocurrent and photocatalytic efficiency were dependent on the thermal decomposition times. The enhanced photoelectrochemical properties of TiO2 NTs/Fe2O3 could be attributed to the improvement of charge separation derived from the coupling effect of TiO2 NTs and Fe2O3 nanocomposite. PMID- 26682403 TI - Novel Synthesis of Magnetic Agar and Its Application in Cu Ions Adsorption. AB - The fabrication of magnetic agar based on chemical precipitation is presented. The magnetic agar has been prepared by seeping NaOH solution into solid agar gel containing Fe2+ and Fe3+. The solid agar gels were heated to become solution and magnetic characteristic disappeared. When the temperature of the solution returned to room temperature, solid magnetic agar was vividly obtained again. The prepared magnetic agars were characterized by Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) that provided morphological and dimensional characteristic of nanometric magnetic nanoparticles embedded within the agar gel. Finally, magnetic agars were used for the adsorption of Cu2+ ion. The adsorption rate of Cu2+ ion reached 92.5% when Cu2+ ion concentration was 250 mg/L and the addition of magnetic agar was 8 g/L. PMID- 26682404 TI - Modification of Optical, Structural and Dielectric Properties of MeV Ions Irradiated PS/Cu Nanocomposites. AB - In order to study structural, thermal, optical and dielectric behaviors of composites, the films of Cu/polystyrene nanocomposites were synthesized at different concentrations of Cu-nanoparticles. These polymer nanocomposites were irradiated with carbon (85 MeV) and silicon (120 MeV) ions at different fluences. The samples were characterized using different techniques viz: X-ray diffraction, UV-visible spectroscopy, differential scanning calorimetry, and impedance gain phase analyzer. A noticeable increase in the intensity of X-ray diffraction peaks was observed after irradiation with 120 MeV Si-ions, which may be attributed to radiation-induced cross-linking in polymer. Optical properties like band gap was estimated for pure polymer and nanocomposite films from their optical absorption spectra in the wavelength region 200-800 nm. It was found that the band gap value shifted to lower energy (from 4.38 eV to 3.40 eV) on doping with silver nanoparticles and also upon irradiation. Differential scanning calorimetry analysis revealed an increase in the glass transition temperature upon irradiation, which may be attributed to cross linking of polymer chain due to ion beam irradiation which is also corroborated with XRD analysis. Dependence of dielectric properties on frequency, ions and filler concentration was studied. The results revealed the enhancement in dielectric properties after doping nanoparticles and also upon irradiation. It was observed that the effect of Si beam is more effectual than the C-beam because of large electronic energy loss of heavy ion. PMID- 26682405 TI - Comparative Studies of Spinel MnFe2O4 Nanostructures: Structural, Morphological, Optical, Magnetic and Catalytic Properties. AB - Spinel MnFe2O4 nanostructures with two different morphologies such as nanoflakes (NFs) and nanoparticles (NPs) were synthesized by a simple microwave-assisted combustion (MACM) and conventional combustion (CCM) methods respectively. Powder X-ray diffraction (XRD) study showed that the samples have pure cubic spinel phase and the average crystallite size is found to be 15.13 +/- 2 nm and 24.38 +/ 13 nm for NFs and NPs respectively. The calculated lattice parameter values of the samples NFs and NPs are 8.476 and 8.474 A respectively. The morphology of the samples was recorded using high resolution scanning electron microscope (HR-SEM) analysis and was found that nanoflakes and nanoparticles morphologies by MACM and CCM methods respectively. Energy dispersive X-ray (EDX) results showed that the composition of the elements was relevant as expected from these combustion methods. The optical properties of the as-prepared nanostructures were also investigated by UV-Visible Diffuse Reflectance Spectroscopy (DRS) and Photoluminescence (PL) Spectroscopy. The energy band gap (E(g)) of the sample NFs is 1.78 eV, whereas the sample NPs has 1.75 eV. The magnetic properties were investigated using the Vibrating Sample Magnetometer (VSM) at room temperature and the hysteresis loops confirmed the super-paramagnetic behavior for both samples with saturation magnetization (M(s)) values in the range of 59.29 +/- 11 and 66.78 +/- 06 emu/g for the samples NFs and NPs respectively. The oxidation of benzyl alcohol into benzaldehyde reached a maximum of 87.65% for MnFe2O4 NFs, whereas for MnFe2O4 NPs, the conversion was only 69.43% with 100% selectivity. PMID- 26682406 TI - Synthesis and Characterization of Nd(3+)-Doped CaF2 Nanoparticles. AB - The Ca(1-x)F(2+x):Nd(x) nanoparticles were synthesized by chemical direct precipitation method. X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Image analyzer, absorption spectrum and transmittance were taken to characterization the phases, morphologies, sizes, size distribution and optical properties of the samples. The results indicate that the Ca(1-x)F(2+x):Nd(x) samples can be rationally modified in size and morphology by altering the Nd3+ ions doping concentration. With increasing concentration of Nd3+ ions, the particle size decreased from 24 to 14 nm, the intensity of the diffraction peaks decreased, the Ca(1-x)F(2+x):Nd(x) particles aggregated ion of the formed clusters which should have an effect on both speed and orientation of the particles growth. The transmittance of ceramics with a thickness of 2 mm showed that the transmittance can reach 90% when the doping concentration was 5%, which should be profitable for LD pumping. PMID- 26682407 TI - Synthesis and Electro-Catalytic Properties of Platinum Supported on Graphene for Methanol Oxidation. AB - Graphene serves as excellent support material in the synthesis of metal nanoparticle-graphene electrocatalysts. Highly active and stable Pt/Graphene electrocatalysts for the application of direct methanol fuel cells were developed. The oxygen/carbon ratio of graphene supports were tuned by various chemical methods. Pt nanoparticles with a narrow distribution of particle sizes were well dispersed on graphene. An increased catalytic activity and stability were achieved due to an increased graphitization degree of graphene when the Pt/Graphene was deoxidized during Ar/H2 reduction. The activity of Pt/Graphene towards methanol oxidation reaction and its stability was higher compared to Pt/Carbon. This study suggests a bi-functional effect of both graphitization and the oxygenated groups on the catalytic activity. PMID- 26682408 TI - Facile Fabrication of Cobalt Oxide Nanoflowers on Ni Foam with Excellent Electrochemical Capacitive Performance. AB - A facile chemical route was developed to fabricate cobalt oxide nanoflower (NF) on nickel foam substrate. The morphology, microstructure and crystalline form of the cobalt oxide NF were investigated by scanning electron microscopy, X-ray photoelectron and X-ray diffraction. The capacitive performance of the prepared cobalt oxide NF was investigated by cyclic voltammetry, electrochemical impedance and galvanostatic charge-discharge test. The results show that the cobalt oxide NF shows high specific capacitance of 2612.0 F x g(-1) in 6.0 M aqueous KOH electrolyte at 4 A x g(-1) and excellent cyclic stability with capacity retention of 85.3% after 2000 cycles at 30 a x g(-1). PMID- 26682409 TI - Hydrothermal Synthesis and Electrochemical Properties of Spherical alpha-MnO2 for Supercapacitors. AB - In the present work, spherical alpha-MnO2 with a high specific capacitance was synthesized by a two-step hydrothermal route. MnCO3 precursors were first prepared by a common hydrothermal method, and then converted to alpha-MnO2 via a hydrothermal reaction between the precursors and KMnO4 solutions. The effects of hydrothermal temperature on the morphology, crystal structure and specific area of the MnO2 were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD) and BET measurements. The electrochemical capacitive properties of the manganese dioxides with different morphologies and structures were evaluated by cyclic voltammetry and galvonostatic charge-discharge tests. The results showed that the temperature in the second hydrothermal step had prominent impact on the capacitive properties of a-MnO2. The MnO2 synthesized at 150 *C exhibited a highest specific capacitance of 328.4 Fx g(-1) at a charge-discharge current density of 100 mA x g(-1). PMID- 26682410 TI - Photoluminescence as a Probe of the Electrical Charge Dependence of Gold Nanoparticles. AB - Electro-optical switching can be achieved by changing the optical absorption of metal nanoparticles by adding or removing electrical charge, corresponding to increased, respectively, decreased electron density. In this work a different approach is taken by changing the photoluminescence properties as a function of electrical charge on gold nanoparticles. Whereas larger gold nanoparticles (diameter d = 5 and 10 nm), exhibiting a plasmon resonance peak in the absorption spectrum, were used to measure changes of the optical absorption spectrum upon electrical charging, for smaller gold nanoparticles (d = 2 and 5 nm) electrical charging was observed via changes of the photoluminescence. Increase and decrease in photoluminescence was observed at positive and negative applied potentials, respectively. The relation between changes of optical absorption and photoluminescence for the 5 nm particles by electrical charging provides information on the influence of the charge state on the electronic properties and therefore the optical transition probability. The reported observation that not only the optical absorption, but also the photoluminescence is affected by alteration of the electrical charge onto gold nanoparticles may open a new way towards electro-optical switching and bio-sensing. PMID- 26682411 TI - Enhancement of Electrical Properties of Nanostructured Polysilicon Layers Through Hydrogen Passivation. AB - The light absorption of polysilicon planar junctions can be improved using nanostructured top surfaces due to their enhanced light harvesting properties. Nevertheless, associated with the higher surface, the roughness caused by plasma etching and defects located at the grain boundary in polysilicon, the concentration of the recombination centers increases, leading to electrical performance deterioration. In this work, we demonstrate that wet oxidation combined with hydrogen passivation using SiN(x):H are the key technological processes to significantly decrease the surface recombination and improve the electrical properties of nanostructured n(+)-i-p junctions. Nanostructured surface is fabricated by nanosphere lithography in a low-cost and controllable approach. Furthermore, it has been demonstrated that the successive annealing of silicon nitride films has significant effect on the passivation quality, resulting in some improvements on the efficiency of the Si nanostructure-based solar cell device. PMID- 26682413 TI - The Effects of Film Thickness and Evaporation Rate on Si-Cu Thin Films for Lithium Ion Batteries. AB - The reversible cyclability of Si based composite anodes is greatly improved by optimizing the atomic ratio of Si/Cu, the thickness and the evaporation rates of films fabricated by electron beam deposition method. The galvanostatic test results show that 500 nm thick flim, having 10%at. Cu-90%at. Si, deposited with a moderate evaporation rate (10 and 0.9 A/s for Si and Cu respectively) delivers 2642.37 mAh g(-1) as the first discharge capacity with 76% Coulombic efficiency. 99% of its initial capacity is retained after 20 cycles. The electron conductive pathway and high mechanical tolerance induced by Cu atoms, the low electrical resistivity of the film due to Cu3Si particles, and the homogeneously distributed nano-sized/amorphous particles in the composite thin film could explain this outstanding electrochemical performance of the anode. PMID- 26682412 TI - Polymer Nanocomposites Based Thermo-Sensitive Gel for Paclitaxel and Temozolomide Co-Delivery to Glioblastoma Cells. AB - In this work, we have reported the preparation and optimization of paclitaxel (PTX) and temozolomide (TMZ) loaded monomethoxy (polyethylene glycol)-poly(D, L lactide-co-glycolide) (mPEG-PLGA) nanocomposite which is a thermo-sensitive gel delivery system to glioblastoma. We utilized the orthogonal design and homogeneous design for the optimal drug-loaded nanoparticles (NPs) and composite gel prescription, respectively. The physicochemical characteristics of NPs and rheological properties of the gel were analyzed. Then the in vitro release of the gel was determined with a membrane-less diffusion system. Finally, the cytotoxic and apoptosis-inducing effects of the gel on the human malignant glioblastoma cell line U87 and C6 rat glioblastoma cell line were evaluated by MTT and flow cytometry apoptosis assay, respectively. The transmission electron microscopy (TEM) analysis revealed the optimized NPs with a relatively uniform diameter and distribution. The homogeneous design and rheological determination showed that the optimized gel prescription was 250 mg/mL Pluronic F127 (F127), 0.5% hydroxy propyl methylcellulose (HPMC-100M), 0.5% Pluronic F68 (F68), 0.5% sodium alginate (SA) and suitable NPs, which possessed the appropriate gelation behaviors: gelation temperature 28.01 degrees C, gelation time 127.1 s and corrosion speed 0.1892 g/cm2 x hr; and rheological properties: suitable elasticity modulus, viscosity modulus and low phase angle. The in vitro results suggested that the PTX and TMZ were sustainedly released from nanoparticles or the composite gel, and the release and elimination time greatly prolonged; and the composite gel possessed much higher growth-inhibiting effect and apoptosis-inducing rate in U87 and C6 cells than other formulations. These findings demonstrated that the optimal gel was a promising delivery system for the interstitial chemotherapy to glioblastoma. PMID- 26682414 TI - Single-Walled Carbon Nanotubes Functionalized with Carboxylic Acid for Fabricating Polymeric Composite Microstructures. AB - Carbon nanotube composites are promising materials for mechanical and electrical applications. However, methodologies to incorporate carbon nanotubes in polymeric matrices are on high demand, especially for fabricating devices in the micro nanoscale. In this paper we show the fabrication of 3D polymeric microstructures with functionalized single-walled carbon nanotubes (SWCNT), by means of two photon polymerization (2PP). We used a range of SWCNT concentrations (0.01-1 wt%) in the resin to fabricate the composite material. Scanning electron microscopy images show the fabricated microstructures surface quality. Raman spectroscopy was used to confirm the presence and evaluate the distribution of SWCNT in the microstructures. Atomic force microscopy was used to evaluate the mechanical properties of the fabricated microstructures. PMID- 26682415 TI - Mesoporous Europium-Doped Titania Nanoparticles (Eu-MTNs) for Luminescence-Based Intracellular Bio-Imaging. AB - Monodisperse and mesoporous europium (Eu)-doped titania nanoparticles (denoted as Eu-MTNs) were prepared by a co-synthesis method with the presence of a cationic surfactant (i.e., CTAB). A maximum loading amount of 8 mol% of Eu could be successfully incorporated into the framework of MTNs. The synthesized Eu-MTNs samples were characterized with X-ray diffraction (XRD) and scanning electron microscopy (SEM), with their luminescent property examined by photoluminescence (PL). Under ultraviolet irradiation, the Eu-MTNs samples exhibit several characteristic luminescence corresponding to 5D0-7F(j) for Eu+3 ions, which can be attributed to the energy transfer from titania nanocrystallite to Eu3+ ions dispersed in amorphous mesoporous titania region. The potential intracellular bio imaging application of the synthesized Eu-MTN nanoparticles was demonstrated with a breast cancer cell line (i.e., BT-20). High biocompatibility and strong luminescence of the Eu-MTNs show great potential in biomedical applications. PMID- 26682416 TI - Effects of Graphene Oxide Modified Sizing Agents on Interfacial Properties of Carbon Fibers/Epoxy Composites. AB - A kind of graphene oxide (GO) modified sizing agent was used to improve the interfacial properties of carbon fibers/epoxy composites. The surface topography of carbon fibers was investigated by scanning electron microscopy (SEM). The surface compositions of carbon fibers were determined by X-ray photoelectron spectroscopy (XPS) and the interfacial properties of composites were studied by interlaminar shear strength (ILSS). The results show that the existence of GO increases the content of reactive functional groups on carbon fiber surface. Thus it enhances the interfacial properties of carbon fibers/epoxy composites. When GO loading in sizing agents is 1 wt%, the ILSS value of composite reaches to 96.2 MPa, which is increased by 27.2% while comparing with unsized carbon fiber composites. Furthermore, the ILSS of composites after aging is also increased significantly with GO modified sizing agents. PMID- 26682417 TI - The Facile Hydrothermal Preparation of Orthorhombic WO3 With (001) Facet and Its Photocatalytic Performance. AB - The orthorhombic WO3 nanoplates with (001) facet were fabricated via a facile hydrothermal process, using HBF4 as the acid source. The products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM) and UV-vis diffused reflectance spectroscopy (DRS), respectively. It indicated that the obtained product was orthorhombic WO3 (JCPDS No. 20-1324). And the energy gap was estimated to be 2.52 eV by the intersection point of the tangent of the absorption edge and the baseline. It was affirmed that WO3 crystalline grew along the (001) direction, indicating the product was exposed with (001) facet. The photocatalytic activity of (001) WO3 nanoplates was investigated on the degradation of Rhodamine B (RhB). It demonstrated that photocatalysts exhibited obvious photocatalytic performance under visible light irradiation. The degradation rate of RhB with the typical product reached 95% after being irradiated for 5 h. It indicated that the photocatalytic efficiency of WO3 could be improved by controlling the crystal growth and its morphology. PMID- 26682418 TI - Biosynthesis and Characterization of Silver Nanoparticles from Methanol Leaf Extract of Cassia didymobotyra and Assessment of Their Antioxidant and Antibacterial Activities. AB - The biosynthesis of silver nanoparticles (AgNPs) was achieved for the first time using methanol leaf extract of C. didymobotyra and their in vitro antioxidant and antibacterial activities were also evaluated. Methanol leaf extracts of C. didymobotyra after mixing with AgNO3 solution showed the change in color from light brown to dark yellowish brown within 1 hour. UV-visible spectroscopy study showed the surface plasmon resonance at around 420 nm clearly indicating the biosynthesis of AgNPs. Transmission Electron Microscopy (TEM) analysis proved the presence of biosynthesized AgNPs in spherical shape with huge disparity in sizes. The average size of biosynthesized nanoparticle was about 18 nm. The occurrence of face centered cubic shapes of nanoparticles was established by X-ray diffraction (XRD) patterns. Further, Fourier transform infrared spectroscopy (FTIR) study showed the possible capping of AgNPs because of the active biomolecules present in the methanol leaf extract of C. didymobotyra. The antioxidant activities of biosynthesized AgNPs were evaluated by 1,1-diphenyl-2 picryl hydrazyl (DPPH) radical scavenging assay and found that AgNPs demonstrated a strong antioxidant properties compared to methanol leaf extract. Nevertheless, the biosynthesized AgNPs exhibited a strong antibacterial activity against all the tested human pathogenic bacterial strains compared to crude methanol leaf extract of C. didymobotyra. Thus, it is concluded that these biosynthesized AgNPs are cost effective, eco-friendly in nature and could be applied for developing new antibacterial drugs and other biomedical applications in near future. PMID- 26682419 TI - Syntheis and Photocurrent Performance of Graphene Oxide-CdTe/CdS Nanocomposite. AB - Graphene with two-dimensional carbon nanostructures provides a potent strategy to enhance optoelectronic performance of semiconductor nanoparticles based light harvesting assemblies. Graphene oxide-CdTe/CdS (GO-CdTe/CdS) nanocomposites were successfully prepared by CdTe/CdS quantum dots (QDs) formed on the surface of graphene oxide sheets. The structure and optical properties of GO-CdTe/CdS nanocomposites were studied in detail. Photoluminescence measurements showed that the integration of CdTe/CdS QDs with graphene oxide significantly decreased its photoluminescence, which indicated effective transfer of photo-excited electrons from CdTe/CdS to graphene oxide. The generation of photocurrent on illumination of the GO-CdTe/CdS nanocomposite was studied. Significant enhancement in photocurrent induced by GO in CdTe/CdS QDs film had also been demonstrated due to increasing the charge separation and electron conduction. PMID- 26682420 TI - Flexible Polymer Dispersed Liquid Crystal Module with Graphene Electrode. AB - Flexible polymer dispersed liquid crystal (PDLC) module based on graphene electrode was presented in this article. We also investigated electromechanical, as well as electro-optical properties of PDLC module with graphene electrodes. Compared to the ITO electrodes, graphene electrodes exhibits higher light transmittance and more stable electromechanical property of under bend test. Due to the excellent mechanical property of graphene electrodes, it is expected that the flexibility of PDLC module could be further enhanced. Meanwhile, with the integration of graphene as the driving electrodes, the threshold voltage V(th) and saturation voltage V(sat) of PDLC module have small change, while the on state transmittance T(on) is increased by 5%, that may attribute to the high transmittance of the graphene. PMID- 26682421 TI - Effect of Capsaicin-Loading Nanoparticles on Gliomas. AB - Capsaicin is recognized as a natural tumor preventive compound and exhibits a remarkable anticancer action. Strong inhibitory role of capsaicin on gliomas has been well documented. However, the use of capsaicin is limited due to its hydrophobicity, low affinity, and short half-life. The present study aimed to explore the physiochemical characteristics of the capsaicin-loading nanoparticles prepared by methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) amphiphilic block copolymer. It also aimed to evaluate the ability of the nanoparticles to cross the blood-brain barrier. Additionally, the uptake of nanoparticles in the glioma cells and its ability to inhibit cell proliferation were tested in human glioblastoma U251 cells. mPEG-PCL amphiphilic block copolymer was synthesized using the ring-opening polymerization method, and the capsaicin-loading nanoparticles were prepared with the solvent diffusion method. In vitro drug release assay revealed that the capsaicin-loading nanoparticles presented a slow release characteristic. Coculture of the human glioblastoma U251 cells and the fluorescein-loading nanoparticles showed the uptake of nanoparticles in U251 cells by endocytosis. We found that the NIR-797 isothiocyanate-loading nanoparticles can cross the blood-brain barrier. In addition, the capsaicin loading nanoparticle showed a remarkable inhibition on the growth of U251 cells. The efficacy of the capsaicin-loading nanoparticles against tumor cells was significantly superior to the capsaicin at low concentrations. It is concluded that the capsaicin-loading nanoparticles can provide an extremely promising approach for chemotherapy of gliomas. PMID- 26682422 TI - Comparative Effect Between Laser and Radiofrequency Heating of RGD-Gold Nanospheres on MCF7 Cell Viability. AB - Gold nanoparticles conjugated to cyclo-[Arg-Gly-Asp-D-Phe-Lys(Cys)] peptides (AuNP-c[RGDfK(C)]) have been reported as systems with specific cell internalization in breast cancer cells. AuNPs have also been proposed as localized heat sources for cancer treatment using laser irradiation or radiofrequency (RF). The aim of this research was to analyze, based on the Mie theory, the AuNP-c[RGDfK(C)] absorption cross-sections (C(abs)) of low-frequency electromagnetic waves (13.56 MHz, lambda = 22 m) and optical frequency waves (laser at lambda = 532 nm) and to compare their effect on MCF7 cell viability as thermal conversion sources in AuNPs (20 nm) located inside cells. Cell viability was assessed in MCF7 cells treated with AuNP-c[RGDfK(C)] or water after exposure to the RF field (200 W, 100 V/cm) or laser irradiation (Irradiance 0.65 W/cm2). In both cases (RF and laser) the presence of nanoparticles in cells caused a significant increase in the temperature of the medium (RF: AT = 29.9 +/- 1.7 degrees C for AuNP compared to DeltaT = 13.0 +/- 1.4 degrees C for water; laser: DeltaT = 13.5 +/- 0.7 degrees C for AuNP compared to 3.3 +/- 0.5 degrees C for water). Although RF induced a higher increase in the temperature of the medium with nanoparticles, the largest effect on the cell viability was produced by laser when nanoparticles were located inside the cells (8.7?0.7% for laser compared to 19.4 +/- 0.9% for RF). The differences obtained in C(abs) values (laser: 3.7 x 10- (16) m2; RF: 7.9 x 10-(23) m2) and the observed effect on MFC7 cell viability support two mechanisms previously proposed "wave energy absorption by AuNPs" when laser is used as a thermal conversion source, and "attenuation of the wave passing through the AuNP suspension" when RF is applied. The AuNP c[RGDfK(C)] nanosystem shows suitable properties to improve hyperthermia treatments under laser irradiation due to a larger heat release inside cells. PMID- 26682423 TI - Green Synthesis of Silver Nanoparticles: Effect of Dextran Molecular Weight Used as Stabilizing-Reducing Agent. AB - This paper describes an easy green chemistry method for the synthesis of silver nanoparticles (AgNPs). The AgNPs were obtained through the use of an aqueous silver nitrate solution (AgNO3), with dextrans aqueous solutions of different molecular weights acting as stabilizing and reducing agent, employing the chemical reduction method. We made a comparative study to determine which molecular weight dextran was the best stabilizing and reducing agent, and it was found that the molecular size of the stabilizing agent is inversely proportional to the size of the nanoparticle synthesized. The formation of the AgNPs was demonstrated by UV-Vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS analysis shows the formation of particles with dendritic structure. TEM shows nanoparticles which are spherical in shape and 1 10 nm in size; also, the clear lattice fringes show highly crystalline AgNPs (FCC). PMID- 26682424 TI - Formation of SnO2 Nanowires Using Thermal Evaporation of SnO. AB - SnO2 nanowires (NWs) were grown on a catalyst-coated silicon wafer via the thermal evaporation of SnO powder at 20-30 mTorr. Three types of catalyst, namely Fe, Pt, and Au, were used for the synthesis of the SnO2 NWs. The results show that Pt and Au can be used for the formation of SnO2 NWs. Depending on the experimental conditions, the diameter and length of the SnO2 NWs obtained with Au catalyst are in the ranges of 20-65 nm and a few hundred nanometers to a few micrometers, respectively. The size of the Au nanocatalyst greatly affects the diameter of the SnO2 NWs. With increasing particle size of the Au catalyst, the diameter of the SnO2 NWs increased. In addition, the results show that the synthesis of SnO2 NWs can be conducted at 500 degrees C, which is compatible with low-temperature processes. PMID- 26682425 TI - Synthesis and Characterization of Mercaptoacetic Acid Capped Cadmium Sulphide Quantum Dots. AB - This paper reports the facile synthesis and detailed characterization of mercaptoacetic acid capped cadmium sulphide (CdS) quantum dots using various cadmium precursors. The mercaptoacetic acid capped CdS quantum dots were prepared by facile and simple wet chemical method and characterized by several techniques such as energy dispersive spectroscopy (EDS), X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, UV-vis. spectroscopy, photoluminescence spectroscopy, high-resolution transmission microscopy (HRTEM) and thremogravimetric analysis. The EDS studies revealed that the prepared quantum dots possess higher atomic percentage of sulfur compared to cadmium due to the coordination of thiolate to the quantum dots surfaces. The X-ray and absorption analyses exhibited that the size of quantum dots prepared by cadmium acetate is larger than the quantum dots prepared by cadmium chloride and cadmium nitrate. The increase in size can be attributed to the low stability constant of cadmium acetate in comparison with cadmium chloride and cadmium nitrate. The FTIR and thermogravimetric analysis showed that the nature of capping molecule on the surface of quantum dots are different depending on the cadmium precursors which affect the emission from CdS quantum dots. Photoemission spectroscopy revealed that the emission of quantum dots prepared by cadmium acetate has high intensity band edge emission along with low intensity trapping state emission. However the CdS quantum dots prepared by cadmium chloride and cadmium nitrate produced only trapping state emissions. PMID- 26682426 TI - Fe3O4@Bi2WO6 Core-Shell Structured Microspheres: Facile Construction and Magnetically Recyclable Photocatalytic Activity Under Visible-Light. AB - Core-shell structured Fe3O4@Bi2WO6 composite microspheres (Fe3O4 microspheres as core and Bi2WO6 nanoplates as shell) have been fabricated in a facile and cost effective reflux way. Such fabricated Fe3O4@Bi2WO6 composites show good visible light driven photocatalytic performance on degradation of rhodamine B (RhB) from solution in presence of H2O2. More importantly, they can be easily harvested from aqueous system for recycle with small loss of their photocatalytic activity upon applying an external magnet. However, this combination of Bi2WO6 photocatalytic activity and Fe3O4 magnetic property endows such composite with a bright perspective in low cost waste water treatment by taking full advantage of solar energy. PMID- 26682428 TI - Synthesis and Characterization of KMnF3:Yb/Er@KMnF3 Upconversion Luminescent Nanocrystals. AB - A hydrothermal method has been developed for preparation of monodispersed and flake KMnF3 upconversion luminescent nanocrystals doped with Yb3+ and Er3+. The prepared nanocystals materials were characterized by XRD, EDX, SEM and TEM. The upconversion emission spectra show that the KMnF3:Yb/Er nanocrystals has a single narrow-band emission centered at 660 nm. This is the firstly reported hydrothermal procedure for synthesis of the flake KMnF3 nanocrystals with single narrow-band upconversion luminescence. Furthermore, a core-shell structure was introduced to synthesize the KMnF3:Yb/Er@KMnF3 nanocrystals and higher luminescence intensity was obtained. PMID- 26682427 TI - Dispersion Characteristics of Multi-Walled Carbon Nanotubes with Gallic Acid. AB - Dispersions of multi-walled carbon nanotubes (MW-CNTs) assisted by non-covalent surface modification and covalent surface modification were prepared using different concentration of gallic acid aqueous solution. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to investigate the dispersion states and effect of MWNTs. FTIR results demonstrate that concentration of gallic acid has great effect on the surface modification of multi-walled carbon nanotubes. With the content of gallic acid increasing, modification effect were firstly increased and then decreased in that the optimal concentration is about 10 MUg/ml as it is its solubility in water. SEM and TEM results also show that gallic acid not only can ensure the integrity of the MW-CNTs, but also can purify it. These results confirmed achievement of a good dispersion state and effect of MW-CNTs with gallic acid. The dispersion mechanism of non-covalent surface modification and covalent surface modification was analyzed. PMID- 26682429 TI - Synthesis of YSZ@Ni Nanoparticle by Modified Electroless Plating Process. AB - Ni-YSZ (Y2O3-stabilized ZrO2) composites with core-shell structure (YSZ@Ni) were produced by modified electroless plating process. It was found that YSZ nanoparticles were well encapsulated by nickel powders at 65 degrees C with pH = 12. The spherical nanopowders had core-shell structure and the shell layer was less than 20 nm. The X-ray diffraction (XRD) analysis inferred the production was composed of YSZ and Ni crystals. In the end, the formation mechanism was discussed. PMID- 26682430 TI - Crystal Structure and Antibacterial Activity of (E)-(5-ethyl-2-styryl-1,3-dioxan 5-yl) Methanol Synthesized with Nanosolid Superacid. AB - A new chiral 1,3-dioxane compound was synthesized by aldol condensation reaction in this paper. The reaction of cinnamic aldehyde with 2.1 equiv. of 2,2 bis(hydroxymethyl) butanol in N,N-dimethylformamide and cyclohexane, nanosolid superacid SO4(2-)/Fe2O3 was applied as catalyst, afforded the new chiral 1,3 dioxane compound (E)-(5-ethyl-2-styryl-1,3-dioxan-5-yl) methanol. The compound was fully characterized with infrared spectra, elemental analysis, melting points, 1H NMR and X-ray diffraction. Single crystal X-ray diffraction analysis revealed that the compound crystallized in the monoclinic system, space group P2(1) with a = 5.717(2) A, b = 11.684(4) A, c = 10.569(4) A, alpha = 90.00 degrees, beta = 99.646(4) degrees, gamma = 90.00 degrees, V = 696.0(4) A3, Z = 2, Dc = 1.185 g/cm(-3), R = 0.0182, MU = 0.081 mm(-1), F(000) = 268. In addition, the antibacterial activities of the compound against Bacillus subtilis, Escherichia coli and Staphylococcus aureus have been investigated. PMID- 26682431 TI - MnO2 Nano-Urchin/Graphene Hybrid Electrodes: Facile Synthesis and Enhanced Supercapacitance Performance. AB - MnO2 with urchin-like nano/micro hierarchical architecture was synthesized through an easy hydrothermal method at low temperature and used to prepare MnO2/graphene hybrid composite as electrode materials through an easy and efficient solution-based method. The MnO2 particles in the composite with 66.7% mass ratio could achieve specific capacitance as high as 451.5 F g(-1) at a scan rate of 10 mV s(-1) and exhibit good cycle stability with 93.8% capacitance retention over 2000 cycles. These properties result from the unique urchin-like nano/micro hierarchical structure of MnO2 as well as the function of graphene in enhancing the conductivity and utilization of MnO2. PMID- 26682432 TI - A Nanostructured Degradable Ureteral Stent Fabricated by Electrospinning for Upper Urinary Tract Reconstruction. AB - A degradable polycaprolactone(PCL)/poly(lactic-co-glycolic acid, LA:GA = 80:20) (PLGA) ureter tubular stent was fabricated by electrospinning. The structure and properties of the stents were investigated by the mechanical property testing, scanning electron microscopy (SEM), degradability test in vitro and MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The stent was transplanted to the dorsal muscle of rabbit to evaluate its tissue compatibility. It was shown that the stent has the nano-structure. The mechanical test showed that with the increase in PCL concentration, the mechanical properties of the stent gradually increased, and it could meet the demands of a urethral stent. The collapse time of different concentration of PCL/PLGA (5%, 15%, and 25%) was 28, 42, and 56 days, respectively. These results provide strong evidence that the degradation time can be increased with the increase in PCL concentration. The results of the MTT assay show that the PCL/PLGA stent had no cytotoxicity. In muscle implantation tests, acute tissue reactions due to operation trauma were seen in all specimens at 1 week. After four weeks, the number of inflammatory cells had decreased significantly. Only a few inflammatory cells were seen in the PCL/PLGA stent group after 12 weeks, and the foreign body reaction was more severe in the control group. Animal orthotopic transplantation experiments of these ureteral stents will be done to evaluate its degradable model and tissue compatibility. PMID- 26682433 TI - Synthesis of Diacid-Assisted Indium Oxide Nanoparticles and Its CO Gas Sensing Activity. AB - Indium oxide (In2O3) is an extreme wide band-gap oxide material with unique electronic and optical properties that is used widely in solar cells, gas sensors and optoelectronic devices. In this study, two types of In2O3 nanostructures were prepared by a simple hydrothermal method using succinic acid (SA) or malonic acid (MA) as the assistant agents. The products were characterized by powder X-ray diffractions and scanning electron microscopy (SEM). SEM of the products showed that the In2O3 nanostructures prepared in the presence of SA have a typical cubic morphology with a length and height of -30 nm, whereas the In2O3 nanostructures synthesized in the presence of MA has an atypical rock shape, length and height of 30 -300 nm. Gas sensitivity measurements suggested that both In2O3 sensors (operated at 350 degrees C) have a good response to carbon monoxide (CO) compared to the commercial In2O3 nanoparticles. The SA-In2O3 sensor showed a shorter response time and stronger response than the MA-In2O3 sensor, suggesting that the improved gas sensing performance can be attributed mainly to the surface area. PMID- 26682434 TI - Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug. AB - In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system. PMID- 26682435 TI - Quantification of the Healing Effect in Hepatic Fibrosis Induced by Chitosan Nano Encapsulated Green Tea in Rat Model. AB - Green tea extract exhibits several beneficial activities for the human body. In the present work, we explored the healing effect of a novel bio-nano particle named 'Chitosan nano-encapsulated green tea extract' at the ultrastructural level by performing experiments on rat hepatocytes. A fixed volume of Chitosan nano encapsulated green tea extract solution was administered orally to a group of adult rats for 25 days, after being treated with carbon-tetrachloride and ethanol doses for 3 weeks. Images of ultra-thin sections of liver samples from these rats were recorded in a transmission electron microscope. Using computational analysis, we probed the images quantitatively and found that Chitosan nano encapsulated green tea extract heals nearly 25% of the sub-cellular area infected with hepatic fibrosis, suggesting its high medicinal value. Scanning electron microscopy was performed to study the topographical changes of cell surface as well as the extracellular matrix network between the hepatocytes, which further confirmed the healing effect. PMID- 26682436 TI - Differential Genomic Effects on Signaling Pathways by Two Different CeO2 Nanoparticles in HepG2 Cells. AB - To investigate genomic effects, human liver hepatocellular carcinoma (HepG2) cells were exposed for three days to two different forms of nanoparticles both composed of CeO2 (0.3, 3 and 30 MUg/mL). The two CeO2 nanoparticles had dry primary particle sizes of 8 nanometers {(M) made by NanoAmor} and 58 nanometers {(L) made by Alfa Aesar} and differ in various other physical-chemical properties as well. The smaller particle has stronger antioxidant properties, probably because it has higher Ce3+ levels on the particle surface, as well as more surface area per unit weight. Nanoparticle M showed a normal dose-response pattern with 363, 633 and 1273 differentially expressed genes (DEGs) at 0.3, 3 and 30 MUg/mL, respectively. In contrast, nanoparticle L showed a puzzling dose response pattern with the most DEGs found in the lowest exposure group with 1049, 303 and 323 DEGs at 0.3, 3 and 30 MUg/mL, respectively. This systems biological genomic study showed that the major altered pathways by these two nano cerium oxides were protein synthesis, stress response, proliferation/cell cycle, cytoskeleton remodeling/actin polymerization and cellular metabolism. Some of the canonical pathways affected were mTOR signaling, EIF2 signaling, fatty acid activation, G2/M DNA damage checkpoint regulation, glycolysis and protein ubiquitination. These two CeO2 nanoparticles differed considerably in their genomic effects. M is more active than L in respect to altering the pathways of mitochondrial dysfunction, acute phase response, apoptosis, 14-3-3 mediated signaling, remodeling of epithelial adherens junction signaling, actin nucleation by ARP-WASP complex, altered TCA cycle and elevated fatty acid concentrations by metabolomics. However, L is more active than M in respect to the pathways of NRF2 mediated stress response and hepatic fibrosis/hepatic stellate cell activation. One major difference in the cell response to nano M and L is that nano M caused the Warburg effect while nano L did not. PMID- 26682437 TI - Nanostructured Anodic Multilayer Dielectric Stacked Metal-Insulator-Metal Capacitors. AB - This paper presents the fabrication of Al2O3/TiO2/Al2O3 metal-insulator-metal (MIM) capacitor using anodization technique. High capacitance density of > 3.5 fF/MUm2, low quadratic voltage coefficient of capacitance of < 115 ppm/V2 and a low leakage current density of 4.457 x 10(-11) A/cm2 at 3 V are achieved which are suitable for analog and mixed signal applications. We found that the anodization voltage played a major role in electrical and structural properties of the thin film. This work suggests that the anodization method can offer crystalline multilayer dielectric stack required for high performance MIM capacitor. PMID- 26682438 TI - Influence of Preparation Methods of Nano Au/MCM-41 Catalysts for Vapor Phase Oxidation of Benzyl Alcohol. AB - The Au/MCM-41 nano catalysts were synthesized from four different methods, viz., homogeneous deposition-precipitation, micro-emulsion, impregnation and polyol and their catalytic activities were tested for the vapor phase oxidation of benzyl alcohol to benzaldehyde. The physico-chemical properties of the catalysts were investigated by XRD, TEM, BET surface area, PSD, CO-chemisorption and XPS techniques. The effect of preparation methods, nature of the metal, support and the metal-support interaction in Au/MCM-41 catalysts were studied for the title reaction. The Au/MCM-41 catalysts synthesized from HDP method has shown higher and better catalytic activity as compared to the catalysts prepared by other methods. PMID- 26682439 TI - Synthesis and Characterization of Zinc Oxide Nanosheets for Dye-Sensitized Solar Cells. AB - Zinc oxide (ZnO) nanosheets were synthesized by a simple and facile hydrothermal process and characterized in terms of their morphological, structural, compositional, optical and photovoltaic properties. The detailed characterization revealed that the synthesized ZnO material possess nanosheet morphologies which are grown in very high density, possessing well-crystallinity with wurtzite hexagonal phase and exhibiting good optical properties. Further, the synthesized ZnO nanosheets were used as photoanode material to fabricate efficient dye sensitized solar cell (DSSC). The fabricated DSSC shows an overall light-to electricity conversion efficiency of -1.57%, open-circuit voltage (V(OC)) of 0.552 V, short-circuit currents (J(SC)) of -7.2 mA/cm2 and fill factors (FF) of 0.40. PMID- 26682440 TI - Modeling of Open-Circuit Voltage of Phenyl-C61-Butyric Acid Methyl Ester-Like Based Bulk-Heterojunction Solar Cells. AB - New materials are currently being sought for use in active layers of bulk heterojunction organic solar cells, and computational modeling plays an important role in this search. Although open circuit voltage (V(oc)) is one of the fundamental quantities that determine the efficiency of a solar cell, there is no consensus on the best way to estimate this magnitude for new materials from calculations of the electronic structure. In this paper, we compare ways of predicting V(oc) values employing a diverse group of blends and conclude that it is possible to have a good prediction tool for organic solar cells based on phenyl-C61-butyric acid methyl ester (PCBM) acceptor molecules. PMID- 26682441 TI - Chain Assemblies from Nanoparticles Synthesized by Atmospheric Pressure Plasma Enhanced Chemical Vapor Deposition: The Computational View. AB - This article refers to the computational study of nanoparticle self-organization on the solid-state substrate surface with consideration of the experimental results, when nanoparticles were synthesised during atmospheric pressure plasma enhanced chemical vapor deposition (AP-PECVD). The experimental study of silicon dioxide nanoparticle synthesis by AP-PECVD demonstrated that all deposit volume consists of tangled chains of nanoparticles. In certain cases, micron-sized fractals are formed from tangled chains due to deposit rearrangement. This work is focused on the study of tangled chain formation only. In order to reveal their formation mechanism, a physico-mathematical model was developed. The suggested model was based on the motion equation solution for charged and neutral nanoparticles in the potential fields with the use of the empirical interaction potentials. In addition, the computational simulation was carried out based on the suggested model. As a result, the influence of such experimental parameters as deposition duration, particle charge, gas flow velocity, and angle of gas flow was found. It was demonstrated that electrical charges carried by nanoparticles from the discharge area are not responsible for the formation of tangled chains from nanoparticles, whereas nanoparticle kinetic energy plays a crucial role in deposit morphology and density. The computational results were consistent with experimental results. PMID- 26682442 TI - Charge Transport in Polypyrrole Nanotubes. AB - True metallic conductivity in conjugated polymers has been major challenge for the last few years. Heeger and co-workers have reported metallic conductivity in bulk polyaniline film, but the problem of metallic transport in their nanophase still remains unexplored. In the recent past, our group had observed metallic conductivity in single nanotube by studying I-V characteristics using Atomic Force Microscopy. In the present work, Polypyrrole (PPy) nanotubes with variable wall thickness have been synthesized by chemical route. Electrical measurements- current-voltage characteristics as well as variation of resistance over the temperature range from 12 K to 300 K for these nanotubes with variable wall thickness, have also been carried out. The conductivity varies widely from semiconductor to metallic as the wall thickness decreases. Transmission Electron Microscopic study, further, confirms that very aligned and ordered polymer chains are formed due to directional growth in thin walled polypyrrole nanotubes, results in true metallic conductivity with a positive temperature coefficient of resistance over the whole temperature range. To the best of our knowledge, there is no such systematic study reported so far which embraces variation of charge transport characteristics with varying wall thickness of conjugated polymer nanotubes involving both I-V and R-T measurements supplementing each other, which being the main focus of this communication. PMID- 26682444 TI - Electrodeposition and Characterization of Hydroxyapatite on TiN/316LSS. AB - The deposition of TiN on stainless steel substrates may improve the stability and compatibility of this material with bone, which may be advantageously exploited for the elaboration of advanced pros- thetic devices. In this work, TiN-coated 316LSS (by way of DC magnetron sputtering) was used as a starting material for investigating the electrochemical post-deposition of hydroxyapatite (HAp) which has a composition close to that of bone. Electrodeposition was carried out starting from an aqueous medium containing solubilized Ca(NO3)2 and NH4H2PO4 in the presence of H2O2. We report the influence of experimental conditions on the morphology of the obtained HAp coating on TiN/316LSS. The effect of applied potential, temperature, H2O2 concentration, pH and duration of reaction were thoroughly discussed on the basis of X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy and Energy Dispersive X-ray Spectroscopy (EDX) results. This method appears advantageous for producing HAp-coated implant materials. PMID- 26682443 TI - DEGylation Enhanced the Stability of Peptide-siRNA Complexes in Serum. AB - Small interfering RNA (siRNA) shows great therapeutic potential due to its ability to regulate gene expression in a highly selective manner, but this application has been limited by effective delivery, partly because of the low nuclease resistance of siRNA in the presence of serum, and inefficient cellular uptake. We previously reported a library of cell-penetrating and amino acid pairing peptides that facilitate effective siRNA delivery to mammalian cells without causing cytotoxicity, but they are unstable within serum-containing medium. Here, we investigated the possibility of conjugating the peptide with diethylene glycol to improve its serum stability without compromising its gene regulation capability. One of the most promising peptides, C6M1, was conjugated with diethylene glycol, and its incorporated siRNA complexes had excellent serum stability and highly efficient cellular uptake with negligible cytotoxicity. The gene-silencing ability of diethylene glycol conjugated-peptide/siRNA complexes was comparable to that of non-conjugated peptide/siRNA at both mRNA and protein levels. Our data demonstrate that conjugating peptides with diethylene glycol is a promising method for improving siRNA delivery by improving its serum stability. PMID- 26682445 TI - Synthesis of ZnO Nanograins by Immersing Zn Powders in Oxalic Acid Solution Plus Thermal Decomposition. AB - A simple and inexpensive method to synthesize ZnO nanograin powders from Zn powders is reported in this paper and phase change from Zn powders to ZnO nanograins during the process is studied in detail. Zinc powders were immersed into 1.0 mol/l oxalic acid aqueous solution for various times and then dried at ambient condition. As-prepared precursors were decomposed in air at temperatures of 200-600 degrees C for 2 hours. As-prepared samples were characterized with scanning electron microscopy, X-ray diffraction and transmission electron microscopy. The results show that the precursors after immersing zinc powders in oxalic acid aqueous solution are ZnC2O4 x 2H2O/Zn(OH)2 dense blocks which consist of 5-10 nm grains. ZnC2O4 x 2H2O/Zn(OH)2 dense blocks decompose into ZnC2O4/ZnO blocks after heating in air at 200 degrees C x ZnC2O4/ZnO blocks further decompose into loose ZnO blocks after heating in air at 400 degrees C and grain sizes of ZnO are - 10 nm in the loose blocks. The phase transitions from Zn powders to ZnO nanograins during the two-step synthesis are analyzed thermodynamically. A physical model is suggested to explain the morphology changes from ZnC2O4 x 2H2O/Zn(OH)2 dense blocks to ZnO loose blocks, based on the volume changes during the phase transitions. PMID- 26682446 TI - Optimizing Calcium Phosphates by the Control of pH and Temperature via Wet Precipitation. AB - A series of calcium phosphates synthesized through a wet precipitation route of hydroxylapatite (HAP) was investigated over a wide range of temperature and pH (25-80 degrees C, and pH 6.5-10.0) using a combination of microscopic and spectroscopic analyses. XRD and FTIR show that monetite and brushite are formed as a single phase at non-ideal conditions of HAP, respectively. From TGA results, it is found that brushite is converted to monetite at a range 175-200 degrees C when heated at the heating rate, 10 degrees C/min. This phase transformation is also observed when brushite is aged at pH 8.5 and 60 degrees C for 24 hr in solution. Morphology of brushite is sensitive to pH variation. At pH 6.5, tabular and platy crystals of brushite are observed whereas needle-like ones are predominant at pH 8.5. For HAP formed at pH 10.0, their shapes tend toward needle like particles as temperature increases. HAP particles at pH 8.5 are very similar in morphology to HAP at pH 10.0, but their lengths are two or three times as great as those at pH 10.0. These observations demonstrate that desired phase and properties of calcium phosphates can be controlled by pH, temperature, and aging time through a wet precipitation method. PMID- 26682447 TI - The Effect of Starting Precursors on Size and Shape Modification of ZrB2 Ceramic Nanoparticles. AB - The formation of ZrB2 nanoparticles through reaction of Zr(n-PrO)4 with H3BO3 and carbon has been studied with different ligands by carbothermal reduction at 1500 degrees C. In the first step, by introducing N, N'-bis (salicylidene)-1,3 diaminopropane (H2salpn) or salicylaldehyde (Hsal) species into reaction mixture, the reaction of the zirconium alkoxide using citric acid and boric acid yielded the zirconium diboride (ZrB2) sol-gel precursors. In the second step, the mixture was heated by introducing the reactant compact into an argon furnace held at 1500 degrees C for 2 h to obtain the final pure phase ZrB2 nanocrystallites with a diameter of about 50 nm. The kind of chelating agent used in the preparation of ZrB2 nanoparticles plays the predominant role on the final product size. This demonstrates that the proper kind of donor atom and a very specific ligand structure are necessary for the reaction of Zr4+ complexes. PMID- 26682448 TI - Superhydrophobic Surfaces with Very Low Hysteresis Prepared by Aggregation of Silica Nanoparticles During In Situ Urea-Formaldehyde Polymerization. AB - We present a new method for the preparation of superhydrophobic materials by in situ aggregation of silica nanoparticles on a surface during a urea-formaldehyde (UF) polymerization. This is a one-step process in which a two-tier topography is obtained. The polymerization is carried out for 30, 60, 120, 180, and 240 min on silicon shards. Silicon surfaces are sintered to remove the polymer. SEM and AFM show both an increase in the area covered by the nanoparticles and their aggregation with increasing polymerization time. Chemical vapor deposition of a fluorinated silane in the presence of a basic catalyst gives these surfaces hydrophobicity. Deposition of this low surface energy silane is confirmed by the F 1s signal in XPS. The surfaces show advancing water contact angles in excess of 160 degrees with very low hysteresis (< 7) after 120 min and 60 min polymerization times for 7 nm and 14 nm silica, respectively. Depositions are successfully demonstrated on glass substrates after they are primed with a UF polymer layer. Superhydrophobic surfaces can also be prepared on unsintered substrates. PMID- 26682449 TI - Dual-Wavelength Light Emission from CdSe/ZnS Quantum Dots on Blue Light-Emitting Diodes. AB - We fabricated light-emitting device by using CdSe/ZnS quantum dots (QDs) on InGaN/GaN blue light-emitting diodes (LEDs) for converting blue emission into green emission. By adding Au nanoparticles (ANPs) to generate localized surface plasmon mode, the integrated intensity of green emission of LEDs with CdSe/ZnS QDs on ANPs is enhanced by about 55%, without any drawback in electrical characteristics of LEDs. This result is attributed to an increased conversion efficiency by resonance coupling between localized surface plasmons in ANPs and excitons in CdSe/ZnS QDs. PMID- 26682450 TI - Cadmium Telluride-Titanium Dioxide Nanocomposite for Photodegradation of Organic Substance. AB - Cadmium telluride-titanium dioxide nanocomposite was prepared by hydrothermal reaction of sol-gel derived titanium dioxide and organically modified cadmium telluride. The crystallinity of titanium dioxide in the nanocomposite was higher than that of pure titanium dioxide obtained by the reaction under the same temperature and pressure conditions, showing that cadmium telluride induced the crystallization of titanium dioxide. Diffuse reflectance spectrum of the nanocomposite showed the higher absorption efficiency in the UV-visible region due to band-gap excitation of titanium dioxide. The nanocomposite significantly showed the improvement of photocatalytic activity for 4-chlorophenol with UV light. PMID- 26682451 TI - Silicon Crystals Formation Using Silicatein-Like Cathepsin of Marine Sponge Latrunculia oparinae. AB - The cDNA fragment encoding the catalytic domain of the new silicatein-like cathepsin enzyme LoCath was expressed in a strain Top10 of Escherichia coli, extracted and purified via nickel-affinity chromatography. Recombinant enzyme performed silica-polymerizing activity when mixed with water-soluble silica precursor-tetrakis-(2-hydroxyethyl)-orthosilicate. Scanning electron microscopy revealed hexagonal, octahedral and beta-tridimit crystals. Energy dispersion fluorescence X-ray spectrometry analysis showed that all these crystals consist of pure silicon oxide. It is the first report about the ability of marine sponge's cathepsin to polymerize silicon, as well as about the structure and composition of the silicon oxide crystal formed by recombinant cathepsin. Further study of the catalytic activity of silicatein and cathepsin will help to understand the biosilification processes in vivo, and will create basis for biotechnological use of recombinant proteins for silicon polymerization. PMID- 26682452 TI - A Special Section on Cutting-Edge Nanosystems for Biomedical Applications. PMID- 26682453 TI - Gold, Silver and Carbon Nanoparticles Grafted on Activated Polymers for Biomedical Applications. AB - Organic polymers have been applied successfully in fields such as adhesion, biomaterials, protective coatings, friction and wear, composites, microelectronic devices, and thin-film technology. In general, special surface properties with regard to chemical composition, hydrophilicity, roughness, crystallinity, conductivity, lubricity, and cross-linking density are required for the success of these applications. Polymers very often do not possess the surface properties needed for these applications. For these reasons, surface modification techniques which can transform these inexpensive materials into highly valuable finished products have become an important part of the plastics industry. In case of biomedical polymers is plasma treatment used for enhancing cell adhesion, growth and proliferation and to make them suitable for implants and tissue engineering scaffolds. Nanoparticles fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Nowadays nanoparticles can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic level precision. In recent years, focus has turned to therapeutic possibilities for such materials. Structures, which behave as drug carriers, antimicrobial agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule-based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications. In this review, we provide insights into immobilization, toxicity and biomedical applications of gold, silver and carbon nanoparticles and discuss their grafting to polymer substrates and the influence on cell-material interactions. The adhesion and the response of cells in contact with the surface play an important role in the cytocompatibility of the implant. It is thus important to understand how cells interact with their environment. The main properties decisive for colonization of a material with cells are surface chemistry, roughness, morphology and polarity, wettability and electrical charge. PMID- 26682454 TI - Hybrid Carbon-Based Nanostructured Platforms for the Advanced Bioreactors. AB - Mankind faces several global challenges such as chronic and acute hunger, global poverty, energy deficiency and environment conservation. Common biotechnologies based on batch, fluidbed and other similar processes are now extensively used for the production of a wide range of products such as antibiotics, biofuels, cultured and fermented food products. Unfortunately, these processes suffer from low efficiency, high energy demand, low controllability and rapid biocatalyst degradation by microbiological attack, and thus still are not capable of seriously addressing the global hunger and energy deficiency challenges. Moreover, sustainable future technologies require minimizing the environmental impact of toxic by-products by implementing the "life produces organic matter, organic matter sustains life" principle. Nanostructure-based biotechnology is one of the most promising approaches that can help to solve these challenges. In this work we briefly review the unique features of the carbon-based nanostructured platforms, with some attention paid to other nanomaterials. We discuss the main building blocks and processes to design and fabricate novel platforms, with a focus on dense arrays of the vertically-aligned nanostructures, mainly carbon nanotubes and graphene. Advantages and disadvantages of these systems are considered. PMID- 26682455 TI - Biomedical Applications of Advanced Multifunctional Magnetic Nanoparticles. AB - In this review, we have presented the latest results and highlights on biomedical applications of a class of noble metal nanoparticles, such as gold, silver and platinum, and a class of magnetic nanoparticles, such as cobalt, nickel and iron. Their most important related compounds are also discussed for biomedical applications for treating various diseases, typically as cancers. At present, both physical and chemical methods have been proved very successful to synthesize, shape, control, and produce metal- and oxide-based homogeneous particle systems, e.g., nanoparticles and microparticles. Therefore, we have mainly focused on functional magnetic nanoparticles for nanomedicine because of their high bioadaptability to the organs inside human body. Here, bioconjugation techniques are very crucial to link nanoparticles with conventional drugs, nanodrugs, biomolecules or polymers for biomedical applications. Biofunctionalization of engineered nanoparticles for biomedicine is shown respective to in vitro and in vivo analysis protocols that typically include drug delivery, hyperthermia therapy, magnetic resonance imaging (MRI), and recent outstanding progress in sweep imaging technique with Fourier transformation (SWIFT) MRI. The latter can be especially applied using magnetic nanoparticles, such as Co-, Fe-, Ni-based nanoparticles, alpha-Fe2O3, and Fe3O4 oxide nanoparticles for analysis and treatment of malignancies. Therefore, this review focuses on recent results of scientists, and related research on diagnosis and treatment methods of common and dangerous diseases by biomedical engineered nanoparticles. Importantly, nanosysems (nanoparticles) or microsystems (microparticles) or hybrid micronano systems are shortly introduced into nanomedicine. Here, Fe oxide nanoparticles ultimately enable potential and applicable technologies for tumor-targeted imaging and therapy. Finally, we have shown the latest aspects of the most important Fe-based particle systems, such as Fe, alpha-Fe2O3, Fe3O4, Fe-Fe(x)O(y) oxide core-shell nanoparticles, and CoFe2O4 MnFe2O4 core-shell nanoparticles for nanomedicine in the efficient treatment of large tumors at low cost in near future. PMID- 26682456 TI - Nanomaterial-Based Approaches for Prevention of Biofilm-Associated Infections on Medical Devices and Implants. AB - Biofilm formation is a major problem in medical device-related infections leading to failure of implant-based therapies. Though various conventional approaches to counter biofilm formation like physical and/or mechanical removal, chemical removal, and the use of antimicrobials exist, they fail due to increased resistance of biofilms. This review discusses various nanomaterial-based approaches such as the use of metallic and metal oxide nanoparticles- and polymer based nanocomposites, which are currently being developed for prevention and treatment of biofilms. Nanoparticles of transition metals and their oxides are toxic to microorganisms and exhibit their toxicity through the generation of reactive oxygen species at concentrations that are non-toxic to eukaryotic cells. Other approaches include the entrapment of bioactive agents in polymer/ceramic nanoparticles, for enhanced anti-biofilm activity due to the synergistic effect between them. These nanomaterial-based approaches could play an important role in control and eradication of biofilm related infections and complications associated with medical devices and implants. PMID- 26682457 TI - Silver Nanoparticles Stabilized Using Chitosan Films: Preparation, Properties and Antibacterial Activity. AB - In this work we present silver nanoparticles coated with chitosan films synthesized by a simple, environmentally friendly method. Silver nanoparticles were prepared and stabilized by reduction of silver nitrate with chitosan without addition of harmful reduction agents. The presence of silver nanoparticles in the solid films was studied by the X-ray diffraction spectroscopy and X-ray photoelectron spectroscopy. Solid films were dissolved and the solution was observed by the ultraviolet-visible spectroscopy and transmission electron microscopy. The amount of silver in the solid samples was studied by atomic absorption spectroscopy. Antibacterial activity of solid films with silver nanoparticles was tested by disc test on two bacterial strains, Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli. The presence of silver nanoparticles was confirmed both in solid film and in solution by the above mentioned methods. The films exhibited strong antibacterial activity against both bacterial strains. These films could be used as a wound dressing, antimicrobial packaging material or for long-term storage of silver nanoparticles for various applications. PMID- 26682458 TI - Optimization of Self-Assembled Chitosan/Streptokinase Nanoparticles and Evaluation of Their Cytotoxicity and Thrombolytic Activity. AB - In this study, the enzyme streptokinase (thrombolysis agent) and chitosan (Cs) nanoparticles were prepared by self-assembly. Using experimental design, chitosan concentration, solution pH and stirring time were studied as independent variables to identify their effects on size, polydispersity index (PDI) and loading efficiency of nanoparticles. Results showed that pH and concentration have a direct effect on size. Additionally, minimum PDI was observed at lowest values of concentration and highest values of stirring time. pH-5.6 was also necessary to obtain the smallest PDI and highest loading efficiency values. The model predicted that to obtain maximum loading efficiency and minimum size along with low PDI, optimum values are 0.5 mg/mL, 5.18 and 30 min for the Cs concentration, solution pH and stirring time, respectively. The corresponding mean +/- SD values for experimentally prepared nanoparticles were 43 +/- 10%, 526 +/- 121 nm, 0.3 +/- 0.2, respectively. MTT and euglobulin clot lysis assays on the optimized nanoparticles showed that chitosan/streptokinase nanoparticles have slightly toxic effect on human fetal lung fibroblast cells (Mrc-5), compared with chitosan and streptokinase alone as a control. Also, thrombolytic activity of encapsulated streptokinase in nanoparticles is decreased slightly in comparison with free streptokinase. However, the preparation keeps a good potency for use as a thrombolytic agent in vivo. PMID- 26682459 TI - Poly(amidoamine) Dendrimers Modified with 1,2-Epoxyhexane or 1,2-Epoxydodecane for Enhanced Gene Delivery Applications. AB - We report a new non-viral gene delivery system based on hydrophobically modified poly(amidoamine) (PAMAM) dendrimers. In this study, the periphery of amine terminated generation 5 (G5) PAMAM dendrimers was partially reacted with 1,2 epoxyhexane and 1,2-epoxydodecane, respectively. The formed hydrophobically modified G5 dendrimers (denoted as G5.NH2-C6 or G5.NH2-C12) were used to complex two different plasmid DNAs (pDNAs) encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The polyplexes formed between vectors and pDNA were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements. We show that the G5.NH2-C6 and G5.NH2-C12 vectors are able to effectively compact the pDNA, allowing for highly efficient gene transfection into a model cell line (HeLa cells) as demonstrated by both Luc assay and confocal microscopic imaging of the EGFP expression. Under the studied N/P ratios (the molar ratio of primary amines of the dendrimers to phosphates in the pDNA backbone) at 2.5 or 5, the transfection efficiency of the dendrimer-based vectors followed the order of G5.NH2-C12 > G5.NH2-C6 > G5.NH2. This enhanced gene transfection capacity is believed to be associated with the enhanced hydrophobic interaction between the vector/pDNA complexes and the relatively hydrophobic cell membranes. The developed hydrophobically modified dendrimers may be used as a promising non viral vector for enhanced gene delivery applications. PMID- 26682461 TI - Electrophoretic Deposition of alpha-Fe2O3/Chitosan Nanocomposite Coatings for Functional and Biomedical Applications. AB - Promising composite coatings based on hematite (alpha-Fe2O3) mesocrystals of size 110 nm and chitosan (CHT) molecules for different biotechnological applications have been successfully obtained by electrophoretic deposition (EPD). Homogeneous and reproducible coatings have been obtained by studying and controlling the chemical interactions between both phases (alpha-Fe2O3 and CHT). A voltage of 25 V and a deposition time of 5 min were chosen as best deposition conditions, which resulted in highly homogeneous coatings with well-distributed alpha-Fe2O3 particles. According to TGA measurements, the content of alpha-Fe2O3 and chitosan in the final composite coating were found to be 74 and 26 wt%, respectively. The presence of both phases in the composite coating was determined by XRD analysis and the coatings microstructure was observed by SEM. PMID- 26682460 TI - One-Step Nanoengineering of Hydrophobic Photosensitive Drugs for the Photodynamic Therapy. AB - Nanoengineering of anticancer therapeutic drugs including photosensitizers is highly desired and extremely required for improved therapeutic efficacy. It remains a formidable challenge to achieve nanostructured colloidal particles directly starting from hydrophobic drugs due to their hydrophobic nature and ready aggregation in aqueous ambient. In this work, we report a facile method for a one-pot preparation of hydrophobic photosensitizer nanoparticles by coating with different types of polyelectrolyte as stabilizing agents. Regardless of negatively or positively charged polyelectrolyte used, including Poly-L-lysine (PLL, MW = 15 k-30 k), PLL (MW = 30 k-70 k), heparin, and hyaluronic acid (HA), the hydrophobic photosensitizer BDEA (2,5-Bis(4 (diethylamino)benzylidene)cyclopentanone) as a model drug can be readily manipulated into stable and well-dispersed nanoparticles with size of average 120 nm. Stabilization presumably contributes to electrostatic repulsion of the adsorbed polyelectrolyte layer onto nanoparticles. Their anticancer activity against the HeLa cell line shows that the endocytic internalization of these nanosystems is associated with antiproliferative effects after irradiation with visible light. The one-step preparation strategy may be an alternative approach for the design of nano-formulations of hydrophobic photosensitive drugs, presenting a potential for photodynamic antitumor therapy. PMID- 26682462 TI - Antitumor Efficacy of Bacillus Calmette-Guerin Loaded Cationic Nanoparticles for Intravesical Immunotherapy of Bladder Tumor Induced Rat Model. AB - For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapy after surgical transurethral resection. Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium of the same family as tuberculosis, that is capable of inducing a local inflammatory response upon instillation into the bladder. Intravesical therapy with BCG has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors than most chemotherapeutic agents used for the same indication. However, compared to intravesical chemotherapy, BCG immunotherapy provokes more pronounced local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, life-threatening or fatal sepsis. Nanoparticles with positive surface charge and mucoadhesive properties were developed to overcome these side effects. Hence, the aim of this study was to optimize and evaluate cationic chitosan (CS) nanoparticles encapsulating BCG in terms of antitumor efficacy after intravesical administration in bladder tumor, induced in rat model. It was found that nanoparticle formulations of 269-375 nm in size can be produced with 42% encapsulation efficiency. The zeta potential was positive and was suitable for intravesical administration. Antitumor efficacy was determined over the parameters of histopathological evaluation, survival rate and mean bladder weight in comparison to treatment with commercial BCG solution. Concerning survival rates, BCG-loaded chitosan nanoparticles resulted in significantly longer survival than BCG commercial product (up to 86 days of survival with no systemic side effects). When compared to healthy bladder weight averages, all groups (especially BCG commercial solution) showed higher bladder weights confirming tumor formation. Histopathological findings confirmed antitumor activity in all treatment groups and optimum findings were observed in groups treated with CS nanoparticles encapsulating BCG. At the same time, significant nanoparticle accumulation in bladder tissues was observed especially for BCG-loaded CS group. In this study, it was clearly observed that cationic CS nanoparticles provide a significantly improved perspective in intravesical immunotherapy of bladder tumors. PMID- 26682463 TI - Adjuvant Effect of Biogenic Selenium Nanoparticles Improves the Immune Responses and Survival of Mice Receiving 4T1 Cell Antigens as Vaccine in Breast Cancer Murine Model. AB - The modification of tumor-associated antigen-based vaccine to elicit a more robust immune response has been addressed in several ways. In the present work, we aimed to investigate the immunomodulatory effect of selenium nanoparticles as an immunoadjuvant in formulation of a tumor-associated antigen-based vaccine in a preventive form. Fortyfive female inbred BALB/c mice five-to-seven weeks old were used and divided into three groups of test and control, each containing fifteen mice. Group one injected by PBS and used as a control. Group two injected by breast tumor cell lysate alone as vaccine. Group three injected by SeNPs with tumor cell lysate as vaccine. All injections were carried out on day fourteen, twentyone and twentyeight of the study. Tumor induction was done at day thirty. Twenty days after tumor induction serum samples were gathered to measure the cytokine assay. Tumor growth and weight of mice as well as delayed type hyper sensitivity (DTH) response were monitored during the study. Results of the present work showed a significant increase in the level of serum IFN-gamma, IL-2, IL-12 and decreased TGF-beta in SeNPs/vaccine injected mice as well as lower tumor volume, more potent DTH responses and longer survival rate in comparison to control and tumor lysate vaccine. Taken together, it can be deduced from this work that SeNPs can be considered as an adjuvant in vaccine in triggering robust immune response against breast cancer. But further evaluations are still needed to find the best formula for this agent in antitumor vaccines. PMID- 26682464 TI - Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design. AB - Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 +/- 10 nm and 185 +/- 70 nm and RVT encapsulation efficiency of 82 +/- 10% and 76 +/- 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters. PMID- 26682465 TI - Bovine Serum Albumin Nanoparticles Containing Amphotericin B: Characterization, Cytotoxicity and In Vitro Antifungal Evaluation. AB - In this study, nanoparticles based on bovine serum albumin (BSA) containing amphotericin B (AmB) were obtained by the desolvation method and characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. After, the effect of nanoparticles on the cytotoxicity of human erythrocytes in vitro and efficacy over strains of Candida spp. were evaluated. The mean particle size was 156 nm and the AmB encapsulation efficiency was over 82%. The in vitro release profile revealed a sustained release of approximately 48% of AmB over 5 days. AmB is present in BSA nanoparticles as monomer. AmB-loaded nanoparticles showed very low index of hemolysis (less than 8%) in 72 h of assay compared to free AmB, which presented 100% of hemolysis in 2 h of incubation. The AmB-loaded BSA nanoparticles were as effective as free AmB against Candida albicans and Candida tropicalis, considering their sustained release profile. Thus, BSA nanoparticles are potential carriers for AmB, reducing its molecular aggregation and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity. PMID- 26682466 TI - Polyplex Micelles with Double-Protective Compartments of Hydrophilic Shell and Thermoswitchable Palisade of Poly(oxazoline)-Based Block Copolymers for Promoted Gene Transfection. AB - Improving the stability of polyplex micelles under physiological conditions is a critical issue for promoting gene transfection efficiencies. To this end, hydrophobic palisade was installed between the inner core of packaged plasmid DNA (pDNA) and the hydrophilic shell of polyplex micelles using a triblock copolymer consisting of hydrophilic poly(2-ethyl-2-oxazoline), thermoswitchable amphiphilic poly(2-n-propyl-2-oxazoline) (PnPrOx) and cationic poly(L-lysine). The two-step preparation procedure, mixing the triblock copolymer with pDNA below the lower critical solution temperature (LCST) of PnPrOx, followed by incubation above the LCST to form a hydrophobic palisade of the collapsed PnPrOx segment, induced the formation of spatially aligned hydrophilic-hydrophobic double-protected polyplex micelles. The prepared polyplex micelles exhibited significant tolerance against attacks from nuclease and polyanions compared to those without hydrophobic palisades, thereby promoting gene transfection. These results corroborated the utility of amphiphilic poly(oxazoline) as a molecular thermal switch to improve the stability of polyplex gene carriers relevant for physiological applications. PMID- 26682467 TI - Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder. AB - BACKGROUND: Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. METHODS: We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. RESULTS: Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. CONCLUSIONS: Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD. PMID- 26682468 TI - A Loss-of-Function Variant in a Minor Isoform of ANK3 Protects Against Bipolar Disorder and Schizophrenia. AB - BACKGROUND: Ankyrin-3 (ANK3) was one of the first genes to reach significance in a bipolar disorder genome-wide association study. Many subsequent association studies confirmed this finding and implicated this gene in schizophrenia. However, the exact nature of the role of ANK3 in the pathophysiology remains elusive. In particular, the specific isoforms involved and the nature of the imbalance are unknown. METHODS: We genotyped a Norwegian sample of 402 patients with bipolar disorder, 293 patients with schizophrenia, and 330 healthy control subjects genome-wide with the Illumina Human Exome BeadChip. We performed allelic association tests at the genome-wide and gene levels and found a significantly associated single nucleotide polymorphism in a splice site of ANK3. We replicated this finding in two other samples and studied the functional effect of this single nucleotide polymorphism by performing quantitative polymerase chain reaction on the affected exon junction in complementary DNA from blood total RNA. RESULTS: The splice site single nucleotide polymorphism (rs41283526) is located in an alternatively spliced exon of ANK3 and has a strong and significant protective effect against bipolar disorder (odds ratio = .31) and schizophrenia (odds ratio = .21). The minor allele of rs41283526 is a loss-of-function variant that disables the correct splicing of the transcript. Data from the BrainSpan human developmental transcriptome show that the exon bearing this variant is expressed only in a minor isoform of ANK3, the transcription of which is initiated in early adolescence. CONCLUSIONS: Our results suggest that an elevated expression of this transcript starting in adolescence may be an important factor in the pathophysiology of schizophrenia and bipolar disorder. PMID- 26682469 TI - Mixed planting with a leguminous plant outperforms bacteria in promoting growth of a metal remediating plant through histidine synthesis. AB - The effectiveness of plant growth promoting bacteria (PGPB) in improving metal phytoremediation is still limited by stunted plant growth under high soil metal concentrations. Meanwhile, mixed planting with leguminous plants is known to improve yield in nutrient deficient soils but the use of a metal tolerant legume to enhance metal tolerance of a phytoremediator has not been explored. We compared the use of Pseudomonas brassicacearum, Rhizobium leguminosarum, and the metal tolerant leguminous plant Vicia sativa to promote the growth of Brassica juncea in soil contaminated with 400 mg Zn kg(-1), and used synchrotron based microfocus X-ray absorption spectroscopy to probe Zn speciation in plant roots. B. juncea grew better when planted with V. sativa than when inoculated with PGPB. By combining PGPB with mixed planting, B. juncea recovered full growth while also achieving soil remediation efficiency of >75%, the maximum ever demonstrated for B. juncea. MUXANES analysis of V. sativa suggested possible root exudation of the Zn chelates histidine and cysteine were responsible for reducing Zn toxicity. We propose the exploration of a legume-assisted-phytoremediation system as a more effective alternative to PGPB for Zn bioremediation. PMID- 26682470 TI - Complementary roles of the Cek1 and Cek2 MAP kinases in Candida albicans cell wall biogenesis. AB - AIMS: To investigate whether Cek2 (as Cek1) is involved in the biogenesis of the fungal cell wall and to uncover differences and similitudes between both proteins. MATERIALS & METHODS: We used molecular genetics to characterize the role of Cek2 in MTL-heterozygous cells. RESULTS: Deletion of CEK2 (similar to CEK1) renders cells sensitive to cell-wall-interfering drugs and, when overexpressed, Cek2 can become phosphorylated upon the same stimuli that activate Cek1. This is dependent on elements of the sterile-vegetative growth (SVG) pathway. Cek2, contrary to Cek1, mediates a transcriptional activity in a C. albicans-adapted two-hybrid system that is essential for Cek1-Cek2 interaction. CONCLUSION: Cek2 has a cryptic role in cell-wall biogenesis and its role is not entirely redundant to Cek1. PMID- 26682472 TI - Underage drinking: prevalence and correlates of risky drinking measures among youth aged 12-20. AB - BACKGROUND: Underage drinking and its effects have been researched extensively. However, no study to date has examined how the levels of drinking that have been defined as risky for adults might relate to youth who have a heightened physiological vulnerability to alcohol. OBJECTIVES: To examine a range of drinking measures that go beyond common measures of youth alcohol use to gain a more detailed understanding of the nature of underage drinking and its associated correlates and outcomes. METHODS: Analyzing data from a 2013 nationally representative US survey, we examined a variety of measures of alcohol use among 24,445 youth (weighted N = 381,155,562), the demographic groups most likely to have reported drinking in these ways, and associations between these measures of drinking and a number of adverse outcomes. RESULTS: On all measures of potentially risky drinking, including meeting diagnostic criteria for an alcohol use disorder, underage drinkers exceeded the rates found for adults. Independent of sex, race, and age, youth who reported drinking in ways that exceeded guidelines set for adults had increased odds of meeting diagnostic criteria for an alcohol, tobacco, or other drug use disorder, and of reporting a number of health problems. CONCLUSIONS: The high rates at which youth report engaging in a range of risky drinking behaviors suggest a need for a more nuanced approach to substance use and mental health screening and interventions in clinical practice. The findings also underscore the need to address apparent misconceptions about what constitutes unhealthy or unsafe alcohol use among youth. PMID- 26682471 TI - Primary care providers' experiences with urine toxicology tests to manage prescription opioid misuse and substance use among chronic noncancer pain patients in safety net health care settings. AB - BACKGROUND: Guideline recommendations to reduce prescription opioid misuse among patients with chronic noncancer pain include the routine use of urine toxicology tests for high-risk patients. Yet little is known about how the implementation of urine toxicology tests among patients with co-occurring chronic noncancer pain and substance use impacts primary care providers' management of misuse. Clinicians' perspectives on the benefits and challenges of implementing urine toxicology tests in the monitoring of opioid misuse and substance use in safety net health care settings are presented in this paper. METHODS: Twenty-three primary care providers from 6 safety net health care settings whose patients had a diagnosis of co-occurring chronic noncancer pain and substance use were interviewed. Interviews were transcribed, coded, and analyzed using grounded theory methodology. RESULTS: The benefits of implementing urine toxicology tests for primary care providers included less reliance on intuition to assess for misuse and the ability to identify unknown opioid misuse and/or substance use. The challenges of implementing urine toxicology tests included insufficient education and training about how to interpret and implement tests, and a lack of clarity on how and when to act on tests that indicated misuse and/or substance use. CONCLUSIONS: These data suggest that primary care clinicians' lack of education and training to interpret and implement urine toxicology tests may impact their management of patient opioid misuse and/or substance use. Clinicians may benefit from additional education and training about the clinical implementation and use of urine toxicology tests. Additional research is needed on how primary care providers implementation and use of urine toxicology tests impacts chronic noncancer pain management in primary care and safety net health care settings among patients with co-occurring chronic non cancer pain and substance use. PMID- 26682487 TI - Role of Electrochemically Activated Solution in Asepsis in Osteoblasts and Chondrocytes in vitro. AB - PURPOSE: Implant infections are severe complications in orthopedic surgery. Treatment using antibiotics is often unsuccessful without removing the implant due to biofilm formation. In this context, antiseptics may be a potential option. These solutions have a wide antimicrobial spectrum but often cause damage to the local cell populations. In these cases, electrochemically activated solutions (ECAS) may be an alternative. METHODS: Staphylococcus aureus was cultured overnight on polyethylene platelets under different growing conditions (standard /-different biofilm inducing conditions). The samples were treated with an ECAS (0%-30%) and analyzed with regard to their antimicrobial efficacy and their effect on biofilm structures by determining the living bacterial count and scanning electron microscopy. Osteoblast and chondrocyte cell lines (MG-63, and CAL-78, respectively) were cultured to confluence and treated with an ECAS. Total cell count, metabolic activity using FDA staining, and proliferation using Ki67 staining were analyzed. RESULTS: ECAS showed antimicrobial activity in concentrations <1%. In cases of biofilm formation, bacterial toxicity could be detected at concentrations from 3.75 -7.5%. At these same concentrations, a visible change in biofilm structure was observed. Regarding biocompatibility rates, up to 7.5% (of osteoblasts) and 3.75% (of chondrocytes) had little influence on metabolic activity and proliferation. CONCLUSION: ECAS provide good antimicrobial efficacy while maintaining high biocompatibility. These results suggest that these solutions may provide promising alternatives in the treatment of implant-associated infections. PMID- 26682473 TI - Structural and Thermodynamic Effects of Macrocyclization in HCV NS3/4A Inhibitor MK-5172. AB - Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound to WT and A156T protease and compared these structures, their molecular dynamics, and experimental binding thermodynamics to the parent compound. We find that the "unique" binding mode of MK-5172 is conserved even when the P2-P4 macrocycle is removed or replaced with a P1-P3 macrocycle. While beneficial to decreasing the entropic penalty associated with binding, the constraint exerted by the P2-P4 macrocycle prevents efficient rearrangement to accommodate the A156T mutation, a deficit alleviated in the linear and P1-P3 analogs. Design of macrocyclic inhibitors against NS3/4A needs to achieve the best balance between exerting optimal conformational constraint for enhancing potency, fitting within the substrate envelope and allowing adaptability to be robust against resistance mutations. PMID- 26682489 TI - Effectiveness of Sonic, Ultrasonic, and Photon-Induced Photoacoustic Streaming Activation of NaOCl on Filling Material Removal Following Retreatment in Oval Canal Anatomy. AB - OBJECTIVE: This study aimed to assess the effectiveness of sonic, ultrasonic and laser [photon-induced photoacoustic streaming (PIPS)] irrigation activation in removing filling remnants from oval root canals after standard canal retreatment procedures with the ProTaper universal rotary retreatment system. METHODS: Twenty eight maxillary first premolars were instrumented with ProTaper NiTi rotary instruments and obturated with gutta-percha and AH Plus sealer using the continuous wave of condensation technique. After storage at 37 degrees C and 100% humidity for 1 week, the specimens were retreated with the ProTaper universal retreatment system for the removal of filling material. Teeth were then randomly assigned into four groups (n = 7): group 1, positive control; group 2, retreated with sonic irrigation; group 3, retreated with ultrasonic irrigation; and group 4, retreated with laser irradiation. The specimens were scanned using micro-CT before instrumentation, after obturation and mechanical retreatment, and after additional activation procedures. The percentage volume of the filling remnants was measured. Specimens were split longitudinally after micro-CT scan, canal walls were examined using scanning electron microscopy (SEM), and the amount of residual filling material was scored. RESULTS: The filling materials' removal efficacy in the three experimental groups was higher than that of the control group (p < 0.05), whereas filling materials ranging from 1.46 +/- 0.30 to 2.21 +/ 0.46 mm(3) remained in the canal in all three experimental groups. Additionally, there was a significantly greater reduction in the amount of filling remnants in the PIPS group than in the sonic and ultrasonic groups (both p < 0.05), and significantly greater reduction in the ultrasonic group than the sonic group (p < 0.05). CONCLUSIONS: Activation of NaOCl with PIPS showed significantly better performance than sonic and ultrasonic techniques in removing the filling remnants following mechanical retreatment of oval root canals. The ultrasonic technique also performed better than the sonic technique. However, none of the additional activation procedures was able to completely eliminate the filling remnants. PMID- 26682488 TI - Depressive symptoms and decision-making preferences in patients with comorbid illnesses. AB - OBJECTIVE: Shared decision-making (SDM) is increasingly promoted in the primary care setting, but depressive symptoms, which are associated with cognitive changes, may influence decision-making preferences. We sought to assess whether elevated depressive symptoms are associated with decision-making preference in patients with comorbid chronic illness. METHODS: We enrolled 195 patients >=18years old with uncontrolled hypertension from two urban, academic primary care clinics. Depressive symptoms were assessed using the 8-item Patient Health Questionnaire. Clinician-directed decision-making preference was assessed according to the Control Preference Scale. The impact of depressive symptoms on decision-making preference was assessed using generalized linear mixed models adjusted for age, gender, race, ethnicity, education, Medicaid status, Charlson Comorbidity Index, partner status, and clustering within clinicians. RESULTS: The mean age was 64.2years; 72% were women, 77% Hispanic, 38% Black, and 33% had elevated depressive symptoms. Overall, 35% of patients preferred clinician directed decision-making, 19% mostly clinician-directed, 39% shared, and 7% some or little clinician-input. Patients with (vs. without) elevated depressive symptoms were more likely to prefer clinician-directed decision-making (46% versus 29%; p=0.02; AOR 2.51, 95% CI 1.30-4.85, p=0.005). Remitted depressive symptoms (vs. never depressed) were not associated with preference. CONCLUSIONS: Elevated depressive symptoms are associated with preference for clinician directed decision-making. We suggest that clinicians should be aware of this effect when incorporating preference into their communication styles and take an active role in eliciting patient values and exchanging information about treatment choice, all important components of shared decision-making, particularly when patients are depressed. PMID- 26682490 TI - Prevalence and correlates of DSM-5 eating disorders in patients with bipolar disorder. AB - OBJECTIVE: To determine prevalence rates and clinical correlates of current DSM-5 eating disorders in patients with bipolar disorder (BP). METHODS: Prevalence rates of current DSM-5- and DSM-IV-defined binge eating disorder (BED), bulimia nervosa (BN), and anorexia nervosa (AN) were assessed with the Eating Disorder Diagnostic Scale (EDDS) in 1092 patients with BP. Psychiatric illness burden was evaluated with five proxy measures of BP illness severity. Medical illness burden was evaluated with the Cumulative Index Rating Scale (CIRS). RESULTS: Twenty seven percent of patients had a current DSM-5 eating disorder: 12% had BED, 15% had BN, and 0.2% had AN. Rates of DSM-5-defined BED and BN were higher than clinical diagnosis rates and rates of DSM-IV-defined BED and BN. Compared with BP patients without an eating disorder, BP patients with a DSM-5 eating disorder were younger and more likely to be women; had an earlier age of onset of BP; had higher EDDS composite scores and higher degrees of suicidality, mood instability, and anxiety disorder comorbidity; and had a higher mean BMI, higher rate of obesity, and higher CIRS total scores. In a logistic regression model controlling for previously identified correlates of an eating disorder, younger age, female gender, and higher BMI remained significantly associated with an eating disorder. LIMITATIONS: The EDDS has not been validated in BP patients. CONCLUSION: DSM-5 defined BED and BN are common in BP patients, possibly more common than DSM-IV defined BED and BN, and associated with greater psychiatric and general medical illness burden. Further studies assessing DSM-5 eating disorders in people with BP are greatly needed. PMID- 26682491 TI - Loss of sexual interest and premenstrual mood change in women with postpartum versus non-postpartum depression: A nationwide community sample of Korean adults. AB - BACKGROUND: Postpartum depression (PPD) is a type of clinical depression that can affect women after childbirth. Few previous studies have explored the association of depressive and physical symptoms among women with PPD in a nationwide community study. METHOD: A total of 18,807 adults, randomly selected, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) (response rate 80.2%). PPD was defined as a major depressive episode that began within 4 weeks after delivery. RESULTS: Of 679 female subjects with major depressive disorder (MDD), 14.0% (n=95) experienced PPD. Subjects with PPD were significantly more likely to have higher income, education, and reside in an urban area, compared to those with non-PPD. No significant differences were found in number of children. Multiple logistic regression revealed that the loss of sexual interest was the only symptom among 23 depressive symptoms that was significantly associated with depressive episodes among individuals with PPD (AOR=1.91, 95% CI 1.01-3.60) when compared with non PPD. Loss of sexual interest was also significantly associated with the subjects with lifetime PPD regardless of depressive episode (AOR=1.93, 95% CI 1.12-3.31). Conversely, loss of confidence and loss of pleasure were less frequent in subjects with PPD. Premenstrual mood change (chi(2)=5.57, p=0.0036) and comorbid alcohol use disorder (chi(2)=5.11, p=0.031) showed a valid association with PPD. CONCLUSIONS: Loss of sexual interest and premenstrual mood change were associated with women with PPD, whereas those with non-PPD were not, thereby suggesting the possible link between sexual hormones and PPD. PMID- 26682492 TI - An examination of the impact of care giving styles (accommodation and skilful communication and support) on the one year outcome of adolescent anorexia nervosa: Testing the assumptions of the cognitive interpersonal model in anorexia nervosa. AB - BACKGROUND: The cognitive interpersonal model predicts that parental caregiving style will impact on the rate of improvement of anorexia nervosa symptoms. The study aims to examine whether the absolute levels and the relative congruence between mothers' and fathers' care giving styles influenced the rate of change of their children's symptoms of anorexia nervosa over 12 months. METHODS: Triads (n=54) consisting of patients with anorexia nervosa and both of their parents were included in the study. Caregivers completed the Caregiver Skills scale and the Accommodation and Enabling Scale at intake. Patients completed the Short Evaluation of Eating Disorders at intake and at monthly intervals for one year. Polynomial Hierarchical Linear Modeling was used for the analysis. RESULTS: There is a person/dose dependant relationship between accommodation and patients' outcome, i.e. when both mother and father are highly accommodating outcome is poor, if either is highly accommodating outcome is intermediate and if both parents are low on accommodation outcome is good. Outcome is also good if both parents or mother alone have high levels of carer skills and poor if both have low levels of skills. LIMITATIONS: Including only a sub-sample of an adolescent clinical population; not considering time spent care giving, and reporting patient's self-reported outcome data limits the generalisability of the current findings. CONCLUSION: Accommodating and enabling behaviours by family members can serve to maintain eating disorder behaviours. However, skilful behaviours particularly by mothers, can aid recovery. Clinical interventions to optimise care giving skills and to reduce accommodation by both parents may be an important addition to treatment for anorexia nervosa. PMID- 26682493 TI - Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications. AB - Bone remodeling relies on the coordinated functioning of osteoblasts, bone forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ~1 MUm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study various aspects of cell-matrix interactions. PMID- 26682494 TI - Role of general practice in the diagnosis of oral cancer. AB - The incidence of oral cancer is increasing in the United Kingdom. There is evidence that early diagnosis and effective treatment improve survival, but the poor 5-year survival rate (50%), which has not improved for several decades, has been attributed to advanced stage at presentation. To investigate the symptoms associated with cancer of the oral cavity and to explore the role of general practitioners (GP) in the identification and referral of patients, we sent 200 patients questionnaires on the route to diagnosis, symptoms, delay in presentation, and outcomes of consultations with their GP. Of 161 respondents, over half (56%) had been referred to secondary care by their GP and a third (32%) by their dentist. The most commonly reported symptoms were a mouth ulcer (32%), a lump in the face or neck (28%), and pain or soreness in the mouth or throat (27%). Fifteen per cent delayed presentation for more than 3 months. After consultation with a GP (n=109), 53% were referred to a specialist, 22% were referred for tests, 12% were told that their symptom was not serious, and 12% were treated for another condition. GPs have an important role in the identification and referral of people with oral cancer, and the clearly recognised symptoms identified in this study can be used to aid assessment and decision-making. Interventions to promote the prompt identification of oral cancer in general practice such as the opportunistic screening of high-risk patients may help to improve the poor survival rates. PMID- 26682496 TI - Peculiar Reactivity of Isothiocyanates with Pentaphenylborole. AB - The reactions of isothiocyanates with the antiaromatic pentaphenylborole were investigated, revealing significantly different outcomes than the analogous reactions with isocyanates. The 1:1 stoichiometric reaction products isolated include a seven-membered BNC5 heterocycle and a fused bicyclic 4/5-ring system. Studies suggest that the seven-membered ring undergoes an intramolecular [2 + 2] electrocyclic ring closure to produce the bicyclic system. The only derivative for which stoichiometry influenced the reaction outcome was 4 methoxyphenylisothiocyanate. The reaction of borole with an excess of 4 methoxyphenylisothiocyanate resulted in the formation of a fused tetracyclic species with two equivalents of isothiocyanate incorporated into the product. Rational pathways for these unusual transformations are presented. PMID- 26682495 TI - Cigarette Smoking and Breast Cancer Risk in Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study. AB - OBJECTIVE: Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS). MATERIALS AND METHODS: The BCHDS is a consortium of three population-based case-control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04-1.96) and among those who smoked >= 31 years (OR 1.95, 95% CI 1.13-3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01-5.21). Among NHW premenopausal women, breast cancer risk was increased for smoking >= 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41). CONCLUSION: Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk. PMID- 26682497 TI - All Ribosomes Are Created Equal. Really? AB - Ribosomes are generally thought of as molecular machines with a constitutive rather than regulatory role during protein synthesis. A study by Slavov et al.[1] now shows that ribosomes of distinct composition and functionality exist within eukaryotic cells, giving credence to the concept of 'specialized' ribosomes. PMID- 26682498 TI - The Spliceosome: The Ultimate RNA Chaperone and Sculptor. AB - The spliceosome, one of the most complex machineries of eukaryotic cells, removes intronic sequences from primary transcripts to generate functional messenger and long noncoding RNAs (lncRNA). Genetic, biochemical, and structural data reveal that the spliceosome is an RNA-based enzyme. Striking mechanistic and structural similarities strongly argue that pre-mRNA introns originated from self-catalytic group II ribozymes. However, in the spliceosome, protein components organize and activate the catalytic-site RNAs, and recognize and pair together splice sites at intron boundaries. The spliceosome is a dynamic, reversible, and flexible machine that chaperones small nuclear (sn) RNAs and a variety of pre-mRNA sequences into conformations that enable intron removal. This malleability likely contributes to the regulation of alternative splicing, a prevalent process contributing to cell differentiation, homeostasis, and disease. PMID- 26682499 TI - The Biochemical Evolution of Protein Complexes. AB - Over the past decade, it became evident that proteins perform critical functions as components of specialized macromolecular complexes. Here, we discuss a recent study by Wan and colleagues, which highlights the significance of protein complexes by studying their conservation in organisms separated by up to a billion years of evolution. PMID- 26682500 TI - Fed and Fasted Single-dose Assessment of Bioequivalence of Dapagliflozin and Metformin Extended-release Fixed-dose Combination Tablets Relative to Single component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects. AB - PURPOSE: In patients with type 2 diabetes mellitus, fixed-dose combinations (FDCs) of antihyperglycemic medications may provide complementary efficacy while reducing tablet burden and improving compliance. The aim of this study was to assess the bioequivalence and tolerability of 2 FDCs of dapagliflozin and metformin extended-release (XR) versus their individual component (IC) tablets. METHODS: An open-label, balanced, randomized, 2-way crossover, 4-arm study was conducted in 129 healthy Brazilian subjects (aged 18-55 years). Two oral doses of the FDCs (5 mg dapagliflozin and 500 mg metformin XR, and 10 mg dapagliflozin and 1000 mg metformin XR) were evaluated in fed and fasted states. FINDINGS: Under fed and fasted conditions the 5 mg dapagliflozin and 500 mg metformin XR FDC showed bioequivalence to its ICs. The 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent to its ICs in fed subjects. Although AUC for the 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent in fasted subjects, the Cmax for metformin was not bioequivalent to its ICs in fasted subjects (upper 90% CI was 127.5%, and thus outside the 80%-125% bioequivalence interval). The small increase in the fasted state is not considered clinically meaningful due to the small magnitude of the difference (9.2%), the lack of metformin Cmax being associated with efficacy or tolerability concerns, and the fasted state not being the recommended state for dosing of metformin XR. The safety profile and tolerability of the FDCs were similar to those of their ICs and no deaths or serious adverse events were reported. IMPLICATIONS: Both FDCs of dapagliflozin and metformin XR were bioequivalent to their ICs in fed and fasted subjects, except for the metformin Cmax from the 10 mg dapagliflozin and 1000 mg metformin XR FDC in fasted subjects. These data support the use of a dapagliflozin and metformin XR FDC in patients with type 2 diabetes mellitus. PMID- 26682501 TI - Diagnostic Emergency Ultrasound: Assessment Techniques In The Pediatric Patient. AB - Emergency ultrasound is performed at the point of care to answer focused clinical questions in a rapid manner. Over the last 20 years, the use of this technique has grown rapidly, and it has become a core requirement in many emergency medicine residencies and in some pediatric emergency medicine fellowships. The use of emergency ultrasound in the pediatric setting is increasing due to the lack of ionizing radiation with these studies, as compared to computed tomography. Utilizing diagnostic ultrasound in the emergency department can allow clinicians to arrive at a diagnosis at the bedside rather than sending the patient out of the department for another study. This issue focuses on common indications for diagnostic ultrasound, as found in the pediatric literature or extrapolated from adult literature where pediatric evidence is scarce. Limitations, current trends, controversies, and future directions of diagnostic ultrasound in the emergency department are also discussed. PMID- 26682502 TI - Tumor-specific pH-responsive peptide-modified pH-sensitive liposomes containing doxorubicin for enhancing glioma targeting and anti-tumor activity. AB - The pH environment in gliomas is acidic. Therefore, in the present research, we selected our previously reported tumor-specific pH-responsive peptide H7K(R2)2 as a targeting ligand, which could respond to the acidic pH environment in gliomas, possessing CPP characteristics. The pH-sensitive liposomes were selected as carriers which could also respond to the acidic pH environment in gliomas triggering encapsulated drug release from these pH-sensitive liposomes. The H7K(R2)2-modified pH-sensitive liposomes containing doxorubicin (DOX-PSL H7K(R2)2) were designed and prepared in order to evaluate their potential targeting of glioma tumor cells and their anti-tumor activity in mice with glioma tumor cells. DOX-PSL-H7K(R2)2 was prepared by the thin-film hydration method followed by remote loading using an ammonium sulfate gradient method. The in vitro release of DOX from pH-sensitive liposomes was tested and the in vitro targeting characteristics of H7K(R2)2-modified liposomes regarding C6 (rat C6 glioma cells) and U87-MG (human glioblastoma cells) were evaluated. The in vivo anti-tumor activity of DOX-PSL-H7K(R2)2 was also investigated in C6 tumor-bearing mice and in U87-MG orthotopic tumor-bearing nude mice. A specific targeting effect triggered by an acidic pH was observed in our in vitro experiments in C6 and U87-MG glioma cells. The pH-triggered DOX release from the pH-sensitive liposomes under acidic conditions was also confirmed in our in vitro experiment. Anti-tumor activity of DOX-PSL-H7K(R2)2 was found in C6 tumor-bearing mice and U87-MG orthotopic tumor-bearing nude mice in in vivo experiments. The antiangiogenic activity of DOX-PSL-H7K(R2)2 was confirmed in C6 tumor-bearing mice in the in vivo experiment. These H7K(R2)2-modified pH-sensitive liposomes containing anti-tumor drugs developed in this study are a promising delivery system involving the response stimuli at the acidic pH in the glioma tumor microenvironment and are suitable for anti-tumor therapy. PMID- 26682503 TI - Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration. AB - We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03MUg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78+/-6.84%) than the groups implanted with the plates without drug (23.6+/-3.81%) (p<0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair. PMID- 26682504 TI - Combined prokaryotic-eukaryotic delivery and expression of therapeutic factors through a primed autocatalytic positive-feedback loop. AB - Progress in bacterial therapy for cancer and infectious diseases is hampered by the absence of safe and efficient vectors. Sustained delivery and high gene expression levels are critical for the therapeutic efficacy. Here we developed a Salmonella typhimrium strain to maintain and safely deliver a plasmid vector to target tissues. This vector is designed to allow dual transcription of therapeutic factors, such as cytotoxic proteins, short hairpin RNAs or combinations, in the nucleus or cytoplasm of eukaryotic cells, with this expression sustained by an autocatalytic positive-feedback loop. Mechanisms to prime the system and maintain the plasmid in the bacterium are also provided. Synergistic effects of attenuated Salmonella and our inter-kingdom system allow the precise expression of Diphtheria toxin A chain (DTA) gene in tumor microenvironment and eradicate large established tumors in immunocompetent animals. In the experiments reported here, 26% of mice (n=5/19) with aggressive tumors were cured and the others all survived until the end of the experiment. We also demonstrated that ST4 packaged with shRNA-encoding plasmids has sustained knockdown effects in nude mice bearing human MDA-MB-231 xenografts. Three weeks after injection of 5*10(6) ST4/pIKT-shPlk, PLK1 transcript levels in tumors were 62.5+/-18.6% lower than the vector control group (P=0.015). The presence of PLK1 5' RACE-PCR cleavage products confirmed a sustained RNAi-mediated mechanism of action. This innovative technology provides an effective and versatile vehicle for efficient inter-kingdom gene delivery that can be applied to cancer therapy and other purposes. PMID- 26682505 TI - Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubble-enhanced sonoporation. AB - More than 1800 gene therapy clinical trials worldwide have targeted a wide range of conditions including cancer, cardiovascular diseases, and monogenic diseases. Biological (i.e. viral), chemical, and physical approaches have been developed to deliver nucleic acids into cells. Although viral vectors offer the greatest efficiency, they also raise major safety concerns including carcinogenesis and immunogenicity. The goal of microbubble-mediated sonoporation is to enhance the uptake of drugs and nucleic acids. Insonation of microbubbles is thought to facilitate two mechanisms for enhanced uptake: first, deflection of the cell membrane inducing endocytotic uptake, and second, microbubble jetting inducing the formation of pores in the cell membrane. We hypothesized that ultrasound could be used to guide local microbubble-enhanced sonoporation of plasmid DNA. With the aim of optimizing delivery efficiency, we used nonlinear ultrasound and bioluminescence imaging to optimize the acoustic pressure, microbubble concentration, treatment duration, DNA dosage, and number of treatments required for in vivo Luciferase gene expression in a mouse thigh muscle model. We found that mice injected with 50MUg luciferase plasmid DNA and 5*10(5) microbubbles followed by ultrasound treatment at 1.4MHz, 200kPa, 100-cycle pulse length, and 540 Hz pulse repetition frequency (PRF) for 2min exhibited superior transgene expression compared to all other treatment groups. The bioluminescent signal measured for these mice on Day 4 post-treatment was 100-fold higher (p<0.0001, n=5 or 6) than the signals for controls treated with DNA injection alone, DNA and microbubble injection, or DNA injection and ultrasound treatment. Our results indicate that these conditions result in efficient gene delivery and prolonged gene expression (up to 21days) with no evidence of tissue damage or off-target delivery. We believe that these promising results bear great promise for the development of microbubble-enhanced sonoporation-induced gene therapies. PMID- 26682507 TI - Beyond starvation: An update on the autophagic machinery and its functions. AB - Autophagy was originally identified as a cytoprotective system that provides emergency backup energy and basic building blocks under starvation condition by digesting self components. Recent advances in the field unveiled that this system also protects cells against multiple types of stress, as well as invasion by pathogens. Consistent with these findings, autophagy has been redefined as a safeguard system that plays a vital role in human pathology, and this realization has led to exponential progress in autophagy research. In this review, we introduce the basic mechanisms of canonical autophagy and also discuss selective autophagy, a set of pathways that target specific cellular components for digestion; in particular, we focus on lysophagy, a recently identified mechanism required for lysosomal homeostasis. PMID- 26682506 TI - The natural history of pancreatic lipoma: Does it need observation. AB - BACKGROUND: Pancreatic lipomas (PL) are a rare, benign mesenchymal neoplasm. Some patients diagnosed with PL are followed radiographically or referred to a second provider, while others are not followed after incidental diagnosis. In this study we describe 74 cases of intrapancreatic lipomas from a single institution over a 12-year period to elucidate the radiologic and clinical natural history of pancreatic lipoma. METHODS: In the period from January 2001 to December 2013, we selected patients over the age of 18 diagnosed with PL based on Ultrasound, CT, and MR imaging. Clinical data were coupled with review of the radiographic image. These patients were retrospectively followed to establish the significance of PL. RESULTS: PL was identified in 0.012% of all patients undergoing cross-sectional imaging during the studied interval. Lipomas ranged in size at diagnosis from 0.1 cm to 4.8 cm. The majority of patients were asymptomatic at presentation. No patient required intervention or exhibited a change in lipoma diagnosis over a median follow up interval of 41.5 months (range 2-145). 47 patients underwent subsequent imaging with a median of two additional exams (range 2-113) over 31 months (range 1-18). 46/47 (98%) patients with subsequent images showed no discernible growth; 1/47 (2%) had a resolution of the lipoma. CONCLUSIONS: Pancreatic lipomas are rare benign mesenchymal neoplasms that exhibit stable size and morphology. They are overwhelmingly asymptomatic. The natural history of pancreatic lipoma is benign. Short-term interval observation is prudent to prove stability and help differentiate from early liposarcoma. Extensive follow-up is not likely necessary for this benign lesion. PMID- 26682508 TI - Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations. AB - BACKGROUND: Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have recently been shown to cause severe intellectual disability with early-onset epilepsy. The specific manifestations of mutations in this gene remain unknown. CASE REPORT: We report two cases of severe intellectual disability accompanied by early-onset epilepsy with continuous delta activity evident on electroencephalography. Both cases presented with developmental delay and repetitive myoclonic seizures in early infancy. Both cases showed continuous high voltage delta activity over both parietal areas when awake, as revealed by interictal electroencephalograms. After the emergence of continuous delta activity, development stagnated. One case showed some development after relief of the seizures and epileptic activity, but drug resistant seizures recurred, and the development again became stagnant. In both cases, a de novo recurrent heterozygous mutation in EEF1A2 [c.364G>A (p.E122K)] was identified by whole exome sequencing. CONCLUSION: This report provides clinical data on epileptic encephalopathy in patients with EEF1A2 mutation. Continuous high-voltage delta activity seen over both parietal areas may be a unique manifestation of EEF1A2 mutation. Epileptic activity may aggravate the effect of the mutation on brain development. PMID- 26682509 TI - Over expression of p21-activated kinase 7 associates with lymph node metastasis in esophageal squamous cell cancers. AB - BACKGROUND: p21-activated kinase 7 is a member of the group II p21-activated kinase (PAK) family which is known to play important role in tumorigenesis and metastasis. However, the expression of p21-activated kinase 7 in esophageal squamous cell cancers and the correlation with clinical parameters has never been investigated. OBJECTIVE: To explore the role of p21-activated kinase 7 in esophageal squamous cell cancers. METHODS: Esophageal squamous cell carcinoma samples were collected and the expression of p21-activated kinase 7 was detected by immunohistochemistry. In vitro cell invasion assay was employed in EC9706 cells and EC9706PAK7 cells. Metastasis related genes were evaluated by Real-time PCR and Western Blot. RESULTS: In 85 samples, 44 (51.8%) samples showed strong expression and expression of PAK7 was significantly correlated with lymph node stage (p= 0.013) and TNM stage (p= 0.041). In vitro invasion assay showed that the invasion ability of EC9706 PAK7 cells increased 2.5 folds compared with EC9706 cells. PAK7 could enhance the protein levels of Vimentin and MMP10, but reduce E-cadherin, TIMP1 and TIMP2. CONCLUSION: PAK7 is overexpressed in human esophageal squamous cell cancer samples and correlated with lymph node metastasis. PMID- 26682510 TI - XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms and risk of clear cell renal cell carcinoma. AB - INTRODUCTION: In the last decade, an increasing number of polymorphisms in DNA repair genes have been identified and their involvement in carcinogenesis was studied. Despite the fact that XRCC3 and XPD DNA repair genes association with several types of cancer was widely studied, their role in the development of clear cell renal cell carcinoma (CCRCC) has not been established in the European population. OBJECTIVE: The objective of this study was to investigate the association of XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms with the risk of CCRCC and the association between these genotypes and CCRCC histopathological prognostic factors (pathologic stage, Fuhrman grade, tumor diameter). METHODS: This study included 73 patients with CCRCC and 100 healthy individuals without cancer. We used the PCR-RFLP method to determine XRCC3 and XPD genotypes. RESULTS: The XPD 751 variant genotype (Lys/Gln) was more frequent in CCRCC patients than in healthy individuals (OR = 2.92, 95%CI: 1.47-5.79, p= 0.001). Regarding the XRCC3 Thr241Met/XPD Lys751Gln combined genotypes a significant difference was found between patients and controls for Thr/Thr+Lys/Gln (OR = 5.44, 95%CI: 2.09-14.15, p= 0.0003) and for Thr/Met+Gln/Gln (OR = 11.2, 95%CI: 1.95-100.4, p= 0.01).No association was found between any of the studied genotypes and histopathological prognostic factors of CCRCC. CONCLUSIONS: Our findings indicate that XPD Lys751Gln polymorphism may be a risk factor for CCRCC. Regarding the XRCC3 Thr241Met polymorphism, an association with CCRCC was found only in XRCC3 Thr241Met/XPD Lys751Gln combined genotypes. PMID- 26682511 TI - Macrophage mannose receptor 1 and S100A9 were identified as serum diagnostic biomarkers for colorectal cancer through a label-free quantitative proteomic analysis. AB - BACKGROUND: Simple blood tests that could be used for early detection are crucial for the ultimate control and prevention of colorectal cancer (CRC). In this study, we performed a serum proteomic analysis of CRC and health volunteers to identify the novel biomarkers involved in CRC. METHOD: A shotgun proteomic method was applied to identify serum proteins in the serum samples of three CRC and three health volunteers using a combination of high-performance liquid chromatography and mass spectrometry. Label-free protein profiling was conducted to quantify the proteins and compare the profiles of the CRC and health volunteers. Two differentially expressed proteins were further validated by western blot analysis. Quantity analysis was performed through enzyme linked immunosorbent assay (ELISA) in serum from 96 healthy and 118 CRC volunteers. RESULTS: Among of the 373 identified proteins, 69 were linked to CRC (33 upregulated and 36 downregulated). The Gene Ontology and DAVID databases were used to identify the location and function of the different proteins. Among the 69 proteins linked to CRC, two proteins, namely, macrophage mannose receptor 1 (MRC1) and S100A9, were verified to be upregulated in CRC by western blot analysis and could be used to identify CRC from healthy volunteers with high accuracy through ELISA analysis. CONCLUSION: MRC1 and S100A9 may contribute to the determination of the mechanisms and screening involved in CRC. PMID- 26682512 TI - The influence of target concentration, equilibration rate constant (ke0 ) and pharmacokinetic model on the initial propofol dose delivered in effect-site target-controlled infusion. AB - One advantage of effect-site target-controlled infusion is the administration of a larger initial dose of propofol to speed up the induction of anaesthesia. This dose is determined by the combination of the pharmacokinetic model parameters, the target setting and the blood-effect time-constant, ke0 . With the help of computer simulation, we determined the ke0 values required to deliver a range of initial doses with three pharmacokinetic models for propofol. With an effect site target of 4 MUg.ml(-1) , in a 35-year-old, 170-cm tall, 70-kg male subject, the ke0 values delivering a dose of 1.75 mg.kg(-1) with the Marsh, Schnider and Eleveld models were 0.59 min(-1) , 0.20 min(-1) and 0.26 min(-1) , respectively. These ke0 values have the attractive feature that, when used to simulate the administration schemes used in two previous studies, predicted effect site concentrations at loss of consciousness were close to those required for maintenance of anaesthesia. PMID- 26682513 TI - Kainate receptor pore-forming and auxiliary subunits regulate channel block by a novel mechanism. AB - KEY POINTS: Kainate receptor heteromerization and auxiliary subunits, Neto1 and Neto2, attenuate polyamine ion-channel block by facilitating blocker permeation. Relief of polyamine block in GluK2/GluK5 heteromers results from a key proline residue that produces architectural changes in the channel pore alpha-helical region. Auxiliary subunits exert an additive effect to heteromerization, and thus relief of polyamine block is due to a different mechanism. Our findings have broad implications for work on polyamine block of other cation-selective ion channels. ABSTRACT: Channel block and permeation by cytoplasmic polyamines is a common feature of many cation-selective ion channels. Although the channel block mechanism has been studied extensively, polyamine permeation has been considered less significant as it occurs at extreme positive membrane potentials. Here, we show that kainate receptor (KAR) heteromerization and association with auxiliary proteins, Neto1 and Neto2, attenuate polyamine block by enhancing blocker permeation. Consequently, polyamine permeation and unblock occur at more negative and physiologically relevant membrane potentials. In GluK2/GluK5 heteromers, enhanced permeation is due to a single proline residue in GluK5 that alters the dynamics of the alpha-helical region of the selectivity filter. The effect of auxiliary proteins is additive, and therefore the structural basis of polyamine permeation and unblock is through a different mechanism. As native receptors are thought to assemble as heteromers in complex with auxiliary proteins, our data identify an unappreciated impact of polyamine permeation in shaping the signalling properties of neuronal KARs and point to a structural mechanism that may be shared amongst other cation-selective ion channels. PMID- 26682515 TI - Massive enlargement of the anterior mandible. PMID- 26682514 TI - Alterations in trace element levels and mRNA expression of Hsps and inflammatory cytokines in livers of duck exposed to molybdenum or/and cadmium. AB - To evaluate the effects of dietary Molybdenum (Mo) or/and Cadmium (Cd) on trace elements and the mRNA expression levels of heat shock proteins (Hsps) and inflammatory cytokines in duck livers. 240 healthy 11-day-old ducks were randomly divided into six groups with 40 ducks in each group, which were treated with Mo or/and Cd at different doses on the basal diet for 120 days. On days 30, 60, 90 and 120, 10 birds in each group were randomly selected and euthanized and then the livers were collected to determine the contents of Mo, Cd, copper (Cu), iron (Fe), zine (Zn), Selenium (Se) and the mRNA expression levels of Hsps, inflammatory cytokines. In addition, liver tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that the mRNA expression of Hsp60, Hsp70, Hsp90, tumor necrosis factor-alpha (TNF alpha), nuclear factor-kappa B (NF-kappaB), and cyclooxygenase-2 (COX-2) were significantly (P<0.01) upregulated in combination groups; Contents of Cu, Fe, Zn, and Se decreased in combined groups (P<0.05) in the later period of the test while contents of Mo and Cd significantly increased (P<0.01); Furthermore severe hepatocyte diffuse fatty, hepatic cords swelling, hepatic sinusoid disappeared, and inflammatory cells infiltrated around the hepatic central vein were observed in Mo combined with Cd groups. The results indicated that dietary Mo or/and Cd might lead to stress, inflammatory response, tissue damage and disturb homeostasis of trace elements in duck livers. Moreover the two elements showed a possible synergistic relationship. And the high mRNA expression of HSPs and inflammatory cytokines may play a role in the resistance of liver toxicity induced by Mo and Cd. PMID- 26682516 TI - Clinicopathologic features, microvessel density, and immunohistochemical expression of ICAM-1 and VEGF in 15 cases of secondary syphilis with oral manifestations. AB - BACKGROUND: Several studies have reported the clinical aspects of oral syphilis, but few papers have considered the involved immunoinflammatory mechanisms. OBJECTIVE: To analyze the clinicopathologic features and expression of immunoinflammatory and vascular proteins in oral secondary syphilis. STUDY DESIGN: Fifteen patients with oral secondary syphilis were included; histologic features were analyzed using hematoxylin-eosin-stained histologic slides and immunohistochemical reactions were performed against intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and CD34. RESULTS: Lesions presented as multiple plaques and ulcers mostly located on the tongue, lips, and palate. They were covered by a stratified epithelium of irregular thickness showing exocytosis associated with a subjacent plasma cell infiltrate arranged in perivascular and perineural patterns. ICAM-1 and VEGF were expressed on endothelial cells and leukocytes, and microvessel density was similar on the superficial and deep regions of the connective tissue. CONCLUSIONS: Expression of immunoinflammatory and vascular proteins was intense, suggesting their participation on the pathogenesis of oral secondary syphilis. PMID- 26682517 TI - Postradiation trismus and its impact on quality of life in patients with head and neck cancer: a commentary. PMID- 26682519 TI - Extra-oral cause of restricted mouth opening in the oncology setting. PMID- 26682518 TI - Molar root-incisor malformation: considerations of diverse developmental and etiologic factors. AB - OBJECTIVE: The objective of this study was to evaluate the variation in the condition referred to as molar root-incisor malformation (MRIM) and elucidate the distribution of affected teeth. This study further aimed to identify associated environmental stressors. STUDY DESIGN: Individuals were identified through retrospective review of dental radiographs and through referral to the investigators. Histologic evaluation included examination of mineralized and decalcified sections of affected first permanent molar teeth. RESULTS: Thirty cases of MRIM were identified, with all having affected first permanent molars with dysplastic root formation. The primary second molars were affected in 57% of the cases, with permanent anterior teeth being involved in 40% of the cases. A variety of medical conditions were associated with MRIM, the most common being neurologic. Several affected individuals reported no significant past medical history or environmental stressors. CONCLUSIONS: The etiology of MRIM remains unclear, and this unique developmental defect of the first permanent molar roots appears to occur in populations throughout the world. Clinicians identifying the MRIM phenotype should carefully evaluate the permanent incisors for associated developmental defects that could result in pulpal necrosis. PMID- 26682520 TI - The Diagnostic Accuracy of Incisional Biopsy in the Oral Cavity. AB - PURPOSE: To determine the accuracy of incisional biopsy examination to diagnose oral lesions. MATERIALS AND METHODS: This retrospective cohort study was performed to determine the concordance rate between incisional biopsy examination and definitive resection diagnosis for different oral lesions. The study sample was derived from the population of patients who presented to the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital (Boston, MA) from January 2005 through December 2012. Inclusion criteria were the diagnosis of an oral lesion from an incisional biopsy examination, subsequent diagnosis from the definitive resection of the same lesion, and complete clinical and pathologic patient records. The predictor variables were the origin and size of the lesion. The primary outcome variable was concordance between the provisional incisional biopsy diagnosis and definitive pathologic resection diagnosis. The secondary outcome variable was type of biopsy error for the discordant cases. Incisional biopsy errors were assessed and grouped into 5 categories: 1) sampling error; 2) insufficient tissue for diagnosis; 3) presence of inflammation making diagnosis difficult; 4) artifact; and 5) pathologist discordance. RESULTS: A total of 272 patients met the inclusion criteria. The study sample had a mean age of 47.4 years and 55.7% were women. Of these cases, 242 (88.9%) were concordant when comparing the biopsy and final resection pathology reports. At histologic evaluation, 60.0% of discordant findings were attributed to sampling error, 23.3% to pathologist discrepancy, 13.3% to insufficient tissue provided in the biopsy specimen, and 3.4% to inflammation obscuring diagnosis. Overall, concordant cases had a larger average biopsy volume (1.53 cm(3)) than discordant cases (0.42 cm(3)). CONCLUSION: The data collected indicate an 88.9% diagnostic concordance with final pathologic results for incisional oral biopsy diagnoses. Sixty percent of discordance was attributed to sampling error when sampled tissue was not representative of the lesion in toto. Multiple-site biopsy specimens and larger volume samples allowed for a more accurate diagnosis. PMID- 26682521 TI - A Medical School Elective Can Promote an Interest in and an Exposure to the Scope of Oral and Maxillofacial Surgery: Education, Exemplars, and Electives. PMID- 26682522 TI - Instrumental and Conventional Interpretations of Behavior Are Associated With Distinct Outcomes in Early Childhood. AB - Four tasks (N = 191, 3- to 6-year-olds) examined the effect of instrumental versus conventional language cues on children's imitative fidelity of a necklace making activity, their memory and transmission of the activity, and their perceptions of functional fixedness. Children in the conventional condition imitated with higher fidelity, transmitted more of the modeled behavior, and showed higher levels of functional fixedness than children in the instrumental condition. There were no differences in children's memory of the activity between conditions demonstrating that memory alone does not explain differences in imitative fidelity. The data demonstrate that children's interpretation of behavior as instrumental or conventional has wide-ranging implications for what children imitate, what they transmit to others, and how they reason about objects' functions. PMID- 26682523 TI - On the role of context in language evolution: Comment on "Towards a computational comparative neuroprimatology: Framing the language-ready brain" by M.A. Arbib. PMID- 26682524 TI - Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. AB - Compelling data suggest that perturbations in microbial colonization of the gut in early-life, influences neurodevelopment and adult brain function. If this is the case, then ensuring the growth of beneficial bacteria at an early age will lead to optimal brain development and maturation. We have tested whether feeding neonatal rats daily (from post-natal days 3-21) with a galacto-oligosaccharide prebiotic (Bimuno(r), BGOS) or a control solution, alters the levels of hippocampal N-Methyl-D-Aspartate receptor (NMDAR) subunits (GluN1, GluN2A, GluN2B), synaptic proteins (synaptophysin, MAP2, and GAP43) and brain-derived neurotrophic factor (BDNF), at post-natal days 22 and 56. The administration of BGOS significantly elevated GluN2A subunits, synaptophysin and BDNF in the hippocampus of 22 day old rats. The effect was also observed on day 56 (26 days after the feeding ceased). The levels of all other proteins (GluN1, GluN2B, MAP2, GAP43) remained unaltered. Increased GluN2A, synaptophysin, BDNF, but not MAP2, may suggest that neonatal BGOS feeding alters neurotransmission rather than synaptic architecture. Although the functional consequences of our findings require further investigation, the current study confirms that the manipulation of gut bacteria in early-life, has central effects that persist until at least young adulthood. PMID- 26682525 TI - Potential role of targeted therapies in the treatment of triple-negative breast cancer. AB - Breast cancer is the most common cancer type that affects women and is the major cause of morbidity and mortality. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype and accounts for 10-20% of all breast cancer cases. TNBC is commonly characterized by the absence of estrogen, progesterone, and the Her2/neu receptor and is usually diagnosed by immunohistochemistry. Mutations in the BRCA1 gene, as well as overexpression of oncogenic kinases, such as human epidermal growth factor receptor 2, vascular endothelial growth factor A, insulin-like growth factor-1 (IGF-1)/IGF-1 receptor, and transforming growth factor-beta1, have been found to be correlated with a higher risk of metastasis and poor overall survival in TNBC patients. The current review briefly discusses the various treatment options including chemotherapeutics and targeted therapies that are available currently for the therapy of TNBC patients and highlights their comparative benefits and disadvantages for clinical application. PMID- 26682527 TI - Long-term exposure to high levels of decabrominated diphenyl ether inhibits CD4 T cell functions in C57Bl/6 mice. AB - In recent years, the adverse health effects of decabrominated diphenyl ether (BDE 209) have raised more concerns as a growing number of studies reported its persistence in the environment and abundance in the human population, especially in occupational environmental compartments and exposed personnel. This study applies our previous animal model simulating occupational exposure to BDE-209 to investigate its potential adverse effects on CD4 T cells. Female C57Bl/6 mice were orally gavaged with BDE-209 at a dose of 800 mg kg(-1) every 2 days for 10 months and the blood of each mouse was collected for analysis. Kinetic changes of the peripheral immune system were investigated from 1 to 5 months of exposure. The chronic effects on cytokine production, proliferation and the antigen specific responses of CD4 T cells were evaluated at 7, 9 and 10 months, respectively. The results have shown that impaired proliferation and cytokine (IFN-gamma, IL-2 or TNF-alpha) production of CD4 T cells were observed in BDE-209 exposed mice, accompanied by increased T regulatory cells in the blood. BDE-209 exposure in vitro also suppressed the reactivity of CD4 T cells at concentrations of 0.01, 0.1, 1 and 10 MUM. Furthermore, we observed weaker antigen-specific CD4 T-cell responses to Listeria monocytogenes infection in the mice exposed to BDE 209, suggesting decreased resistance to exogenous pathogens. Taken together, these observations indicate an impaired cellular immunity after long-term and relative high-dose exposure to BDE-209 in adult mice. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26682528 TI - Electric and Photoelectric Properties of 3,4-Ethylenedioxythiophene Functionalized n-Si/PEDOT:PSS Junctions. AB - Organic/inorganic solid-state junctions play a critical role in tandem artificial photosynthetic devices supported by conducting polymer membranes. Recent work with n-Si/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) hybrid junctions has shown that the electrical behavior is dominated by the passivating groups present on the silicon surface. In this work, the photovoltaic behavior of n-Si/ PEDOT: PSS was investigated with methyl, thiophene, and 3,4 ethylenedioxythiophene (EDOT) groups covalently attached to the Si(111) surface. X-ray photoelectron spectroscopy results demonstrated that complete monolayer coverage was achieved in 3 h and that the organic passivating groups were retained over two months of exposure to ambient conditions with minimal silicon oxidation. All surfaces investigated exhibited similar light-limited photocurrents and bulk-limited open-circuit voltages, and thiophene produced a dramatic reduction of the fill factor attributed to the formation of trap states at the interface. Furthermore, shunt behavior observed near the power-producing regions for the thiophene and EDOT surfaces is indicative of increased recombination events under forward bias and suggests that hole transport across the interface is enhanced. Thus, thiophene- and EDOT-functionalized Si(111) offer similar stabilities and efficiencies to those of methylated surfaces as well as enhanced hole transport to the PEDOT: PSS interface from the n-Si surfaces. PMID- 26682529 TI - Computational modeling of intraocular gas dynamics. AB - The purpose of this study was to develop a computational model to simulate the dynamics of intraocular gas behavior in pneumatic retinopexy (PR) procedure. The presented model predicted intraocular gas volume at any time and determined the tolerance angle within which a patient can maneuver and still gas completely covers the tear(s). Computational fluid dynamics calculations were conducted to describe PR procedure. The geometrical model was constructed based on the rabbit and human eye dimensions. SF6 in the form of pure and diluted with air was considered as the injected gas. The presented results indicated that the composition of the injected gas affected the gas absorption rate and gas volume. After injection of pure SF6, the bubble expanded to 2.3 times of its initial volume during the first 23 h, but when diluted SF6 was used, no significant expansion was observed. Also, head positioning for the treatment of retinal tear influenced the rate of gas absorption. Moreover, the determined tolerance angle depended on the bubble and tear size. More bubble expansion and smaller retinal tear caused greater tolerance angle. For example, after 23 h, for the tear size of 2 mm the tolerance angle of using pure SF6 is 1.4 times more than that of using diluted SF6 with 80% air. Composition of the injected gas and conditions of the tear in PR may dramatically affect the gas absorption rate and gas volume. Quantifying these effects helps to predict the tolerance angle and improve treatment efficiency. PMID- 26682530 TI - Convenient Access to Fluorescent Probes by Chemoselective Acylation of Hydrazinopeptides: Application to the Synthesis of the First Far-Red Ligand for Apelin Receptor Imaging. AB - Herein, we develop a convenient method to facilitate the solution-phase fluorescent labelling of peptides based on the chemoselective acylation of alpha hydrazinopeptides. This approach combines the advantages of using commercially available amine-reactive dyes and very mild conditions, which are fully compatible with the chemical sensitivity of the dyes. The usefulness of this approach was demonstrated by the labelling of apelin-13 peptide. Various fluorescent probes were readily synthesized, enabling the rapid optimization of their affinities for the apelin receptor. Thus, the first far-red fluorescent ligand with sub-nanomolar affinity for the apelin receptor was characterized and shown to track the receptor efficiently in living cells by fluorescence confocal microscopy. PMID- 26682531 TI - Predicting hypocalcaemia post-thyroidectomy: a retrospective audit of results compared to a previously published nomogram in 64 patients treated at a district general hospital. PMID- 26682532 TI - Acute exercise stress promotes Ref1/Nrf2 signalling and increases mitochondrial antioxidant activity in skeletal muscle. AB - NEW FINDINGS: What is the central question of this study? How does acute exercise affect the redox effector factor-1 (Ref1) and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling and its association with mitochondrial H(2)O(2) production and antioxidant capacity? What is the main finding and its importance? Ref1/Nrf2 signalling in skeletal muscles was activated by acute exercise, and this activation was correlated with increased mitochondrial H(2)O(2) content and antioxidant capacity (reduced glutathione and manganese superoxide dismutase). The finding indicates that the oxidative stress induced by acute exercise in skeletal muscle mitochondria is associated with the upregulation of Ref1/Nrf2 signalling and enhancement of antioxidant defense pathways. This mechanism may play a role in preventing cellular oxidative stress resistance during acute exercise. The molecular mechanism of exercise-induced oxidative stress and adaptive activation of antioxidant responses in skeletal muscle has not been fully elucidated. This study aimed to investigate the effect of acute exercise on redox effector factor-1 (Ref1) and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling and associations with mitochondrial H(2)O(2) production and antioxidant mechanisms in skeletal muscles. Groups of male ICR/CD-1 mice were subjected to an acute exercise bout of different durations (45, 90, 120 or 150 min). Muscle tissues (gastrocnemius and quadriceps femoris) were harvested after exercise to measure mitochondrial manganese superoxide dismutase (MnSOD) and copper-zinc superoxide dismutase (CuZnSOD) activities, reduced glutathione (GSH) content and expression of Ref1/Nrf2 genes and Ref1/Nrf2 proteins. The acute exercise increased oxidative stress and activated Ref1/Nrf2 signalling in a time dependent manner, with a linear correlation between the mitochondrial H(2)O(2) content and Ref1/Nrf2 expressions. The GSH content and MnSOD activity were also significantly increased, but CuZnSOD activity was not significantly affected. The findings indicate that the H(2)O(2) production induced by acute exercise in skeletal muscle mitochondria in the mouse is closely associated with upregulation of the Ref1/Nrf2 signalling pathway and enhancement of antioxidant defense components, including GSH and MnSOD. Activation of Ref1/Nrf2/antioxidant defense pathways may play a role in preventing cellular oxidative stress resistance during acute exercise. PMID- 26682533 TI - A prospective randomized trial on the use of Coca-Cola Zero((r)) vs water for polyethylene glycol bowel preparation before colonoscopy. AB - AIM: The study aimed to determine whether Coca-Cola (Coke) Zero is a safe and effective solvent for polyethylene glycol (PEG). METHOD: Between December 2013 and April 2014, 209 healthy adults (115 men, 95 women) scheduled for elective colonoscopy were randomized to use either Coke Zero (n = 100) or drinking water (n = 109) with PEG as bowel preparation. Each patient received two sachets of PEG to dissolve in 2 l of solvent, to be completed 6 h before colonoscopy. Serum electrolytes were measured before and after preparation. Bowel cleanliness and colonoscopy findings were recorded. Palatability of solution, adverse effects, time taken to complete and willingness to repeat the preparation were documented via questionnaire. RESULTS: Mean palatability scores in the Coke Zero group were significantly better compared with the control group (2.31 +/- 0.61 vs 2.51 +/- 0.63, P = 0.019), with a higher proportion willing to use the same preparation again (55% vs 43%). The mean time taken to complete the PEG + Coke Zero solution was significantly faster (74 +/- 29 min vs 86 +/- 31 min, P = 0.0035). The quality of bowel cleansing was also significantly better in the Coke Zero group (P = 0.0297). There was no difference in the frequency of adverse events (P = 0.759) or the polyp detection rate (32% vs 31.2%). Consumption of either preparation did not significantly affect electrolyte levels or hydration status. CONCLUSION: Coke Zero is a useful alternative solvent for PEG. It is well tolerated, more palatable, leads to quicker consumption of the bowel preparation and results in better quality cleansing. PMID- 26682534 TI - Hierarchical Patterning of Cells with a Microeraser and Electrospun Nanofibers. AB - For tissue engineering applications, it is important to develop fabrication strategies for building models with controlled cell distributions in defined structures. Here, a simple, flexible approach (named the MU-eraser strategy) is developed to construct multicell micropatterns. This approach involves pressing a poly(dimethylsiloxane) stamp to erase cells growing on substrates, and seeding other types of cells. The pressing/seeding process can be conducted in any designed pattern at desired time point. In a proof of concept, multicell micropatterns of human lung adenocarcinoma epithelial A549 cells, murine fibroblast (FB) cells and murine osteoblast (OB) cells are achieved on Petri dishes and electrospun sheets. Besides forming multicell micropatterns, the cell orientation can be regulated by microstripes and alignment of nanofibers. On Petri dishes and random fiber sheets, FB and OB cells align along microstripes, while A549 cells do not. However, when growing on aligned fiber sheets, no matter whether solo-cultured or co-cultured, all cells in micropatterns orient along the fibers. Based on this technique, a platform is built up to investigate rates of cell migration and interinvasion under solo-culture and co-culture systems. It is believed that this MU-eraser strategy has promise for biological, pharmaceutical, and biomedical applications. PMID- 26682535 TI - Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas. AB - PROBLEM: Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. METHOD OF STUDY: Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. RESULTS: Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-alpha and IL-1beta secretion. CONCLUSION: We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion. PMID- 26682536 TI - PSYCHOLOGICAL TREATMENT OF DEPRESSION IN COLLEGE STUDENTS: A METAANALYSIS. AB - BACKGROUND: Expanded efforts to detect and treat depression among college students, a peak period of onset, have the potential to bear high human capital value from a societal perspective because depression increases college withdrawal rates. However, it is not clear whether evidence-based depression therapies are as effective in college students as in other adult populations. The higher levels of cognitive functioning and IQ and higher proportions of first-onset cases might lead to treatment effects being different among college students relative to the larger adult population. METHODS: We conducted a metaanalysis of randomized trials comparing psychological treatments of depressed college students relative to control groups and compared effect sizes in these studies to those in trials carried out in unselected populations of depressed adults. RESULTS: The 15 trials on college students satisfying study inclusion criteria included 997 participants. The pooled effect size of therapy versus control was g = 0.89 (95% CI: 0.66~1.11; NNT = 2.13) with moderate heterogeneity (I(2) = 57; 95% CI: 23~72). None of these trials had low risk of bias. Effect sizes were significantly larger when students were not remunerated (e.g. money, credit), received individual versus group therapy, and were in trials that included a waiting list control group. No significant difference emerged in comparing effect sizes among college students versus adults either in simple mean comparisons or in multivariate metaregression analyses. CONCLUSIONS: This metaanalysis of trials examining psychological treatments of depression in college students suggests that these therapies are effective and have effect sizes comparable to trials carried out among depressed adults. PMID- 26682537 TI - The Amsterdam wrist rules: the multicenter prospective derivation and external validation of a clinical decision rule for the use of radiography in acute wrist trauma. AB - BACKGROUND: Although only 39 % of patients with wrist trauma have sustained a fracture, the majority of patients is routinely referred for radiography. The purpose of this study was to derive and externally validate a clinical decision rule that selects patients with acute wrist trauma in the Emergency Department (ED) for radiography. METHODS: This multicenter prospective study consisted of three components: (1) derivation of a clinical prediction model for detecting wrist fractures in patients following wrist trauma; (2) external validation of this model; and (3) design of a clinical decision rule. The study was conducted in the EDs of five Dutch hospitals: one academic hospital (derivation cohort) and four regional hospitals (external validation cohort). We included all adult patients with acute wrist trauma. The main outcome was fracture of the wrist (distal radius, distal ulna or carpal bones) diagnosed on conventional X-rays. RESULTS: A total of 882 patients were analyzed; 487 in the derivation cohort and 395 in the validation cohort. We derived a clinical prediction model with eight variables: age; sex, swelling of the wrist; swelling of the anatomical snuffbox, visible deformation; distal radius tender to palpation; pain on radial deviation and painful axial compression of the thumb. The Area Under the Curve at external validation of this model was 0.81 (95 % CI: 0.77-0.85). The sensitivity and specificity of the Amsterdam Wrist Rules (AWR) in the external validation cohort were 98 % (95 % CI: 95-99 %) and 21 % (95 % CI: 15 %-28). The negative predictive value was 90 % (95 % CI: 81-99 %). CONCLUSIONS: The Amsterdam Wrist Rules is a clinical prediction rule with a high sensitivity and negative predictive value for fractures of the wrist. Although external validation showed low specificity and 100 % sensitivity could not be achieved, the Amsterdam Wrist Rules can provide physicians in the Emergency Department with a useful screening tool to select patients with acute wrist trauma for radiography. The upcoming implementation study will further reveal the impact of the Amsterdam Wrist Rules on the anticipated reduction of X-rays requested, missed fractures, Emergency Department waiting times and health care costs. TRIAL REGISTRATION: This study was registered in the Dutch Trial Registry, reference number NTR2544 on October 1(st), 2010. PMID- 26682538 TI - Evolutionary significance and diversification of the phosphoglucose isomerase genes in vertebrates. AB - BACKGROUND: Phosphoglucose isomerase (PGI) genes are important multifunctional proteins whose evolution has, until now, not been well elucidated because of the limited number of completely sequenced genomes. Although the multifunctionality of this gene family has been considered as an original and innate characteristic, PGI genes may have acquired novel functions through changes in coding sequences and exon/intron structure, which are known to lead to functional divergence after gene duplication. A whole-genome comparative approach was used to estimate the rates of molecular evolution of this protein family. RESULTS: The results confirm the presence of two isoforms in teleost fishes and only one variant in all other vertebrates. Phylogenetic reconstructions grouped the PGI genes into five main groups: lungfishes/coelacanth/cartilaginous fishes, teleost fishes, amphibians, reptiles/birds and mammals, with the teleost group being subdivided into two subclades comprising PGI1 and PGI2. This PGI partitioning into groups is consistent with the synteny and molecular evolution results based on the estimation of the ratios of nonsynonymous to synonymous changes (Ka/Ks) and divergence rates between both PGI paralogs and orthologs. Teleost PGI2 shares more similarity with the variant found in all other vertebrates, suggesting that it has less evolved than PGI1 relative to the PGI of common vertebrate ancestor. CONCLUSIONS: The diversification of PGI genes into PGI1 and PGI2 is consistent with a teleost-specific duplication before the radiation of this lineage, and after its split from the other infraclasses of ray-finned fishes. The low average Ka/Ks ratios within teleost and mammalian lineages suggest that both PGI1 and PGI2 are functionally constrained by purifying selection and may, therefore, have the same functions. By contrast, the high average Ka/Ks ratios and divergence rates within reptiles and birds indicate that PGI may be involved in different functions. The synteny analyses show that the genomic region harbouring PGI genes has independently undergone genomic rearrangements in mammals versus the reptile/bird lineage in particular, which may have contributed to the actual functional diversification of this gene family. PMID- 26682539 TI - Changes in active commuting and changes in physical activity in adults: a cohort study. AB - BACKGROUND: Active travel is associated with greater physical activity, but there is a dearth of research examining this relationship over time. We examined the longitudinal associations between change in time spent in active commuting and changes in recreational and total physical activity. METHODS: Adult commuters working in Cambridge, United Kingdom completed questionnaires in 2009 and 2012, and a sub-set completed objective physical activity monitoring in 2010 and 2012. Commuting was assessed using a validated seven-day travel to work record. Moderate-to-vigorous physical activity was assessed using the Recent Physical Activity Questionnaire and combined heart rate and movement sensing. We used multivariable multinomial logistic regression models to examine associations between change in time spent in active commuting and tertiles of changes in time spent in recreational and total physical activity. RESULTS: Four hundred sixty nine participants (67% female, mean age 44 years) provided valid travel and self reported physical activity data. Seventy-one participants (54% female, mean age 45 years) provided valid travel and objectively measured physical activity data. A decrease in active commuting was associated with a greater likelihood of a decrease in self-reported total physical activity (relative risk ratio [RRR] 2.1, 95% CI 1.1, 4.1). Correspondingly, an increase in active commuting was associated with a borderline significantly greater likelihood of an increase in self reported total physical activity (RRR 1.8, 95% CI 1.0, 3.4). No associations were seen between change in time spent in active commuting and change in time spent in either self-reported recreational physical activity or objectively measured physical activity. CONCLUSIONS: Changes in active commuting were associated with commensurate changes in total self-reported physical activity and we found no compensatory changes in self-reported recreational physical activity. Promoting active commuting has potential as a public health strategy to increase physical activity. Future longitudinal research would be useful to verify these findings. PMID- 26682540 TI - Insulin treatment increases myocardial ceramide accumulation and disrupts cardiometabolic function. AB - BACKGROUND: States of hyperinsulinemia, particularly insulin resistance and type 2 diabetes mellitus, are becoming remarkably common, with roughly half a billion people likely to suffer from the disorder within the next 15 years. Along with this rise has been an associated increased burden of cardiovascular disease. Considering type 2 diabetics treated with insulin are more likely to suffer from heart complications, we sought to determine the specific effect of insulin on ceramide-dependent cardiometabolic risk factors, including insulin resistance and altered heart mitochondrial physiology. METHODS: H9c2 cardiomyocytes and adult mice were treated with insulin with or without myriocin to inhibit ceramide biosynthesis. Insulin and glucose changes were tracked throughout the study and mitochondrial bioenergetics was determined in permeabilized cardiomyocytes and myocardium. RESULTS: Herein, we demonstrate that insulin is sufficient to disrupt heart mitochondrial respiration in both isolated cardiomyocytes and whole myocardium, possibly by increasing mitochondrial fission. Further, insulin increases ceramide accrual in a time-dependent manner, which is necessary for insulin-induced alterations in heart mitochondrial respiration and insulin resistance. CONCLUSIONS: Collectively, these observations have two implications. First, they indicate a pathological role of insulin in heart complications stemming from mitochondrial disruption. Second, they identify ceramide as a possible mediator of insulin-related heart disorders. PMID- 26682541 TI - Specific Features of Dumping Syndrome after Various Types of Gastrectomy as Assessed by a Newly Developed Integrated Questionnaire, the PGSAS-45. AB - AIM: Dumping syndrome is a well-known adverse outcome after gastrectomy, but the precise clinical features have not been described. The aim of this study was to examine global aspects of dumping syndrome and to explore factors affecting the intensity of dumping syndrome in a large cohort using a newly developed integrated questionnaire, the Post-Gastrectomy Syndrome Assessment Scale (PGSAS) 45. METHODS: Eligible questionnaires retrieved from 2,368 patients after 6 types of gastrectomy were analyzed. The incidence, intensity and number of symptoms of early general, early abdominal and late dumping syndrome were examined across various types of gastrectomy, and clinical factors affecting the intensity of each category of dumping syndrome were identified by multiple regression analysis. RESULTS: Dumping syndromes occurred most frequently and strongly in patients who underwent total gastrectomy with Roux-en-Y (TGRY), followed by proximal gastrectomy (PG), distal gastrectomy with Billroth-I, distal gastrectomy with Roux-en-Y, pylorus-preserving gastrectomy (PPG) and local resection (LR), in that order. Significant positive correlations among different categories of dumping syndromes were observed. TGRY, female sex, younger age, division of the celiac branch of the vagus nerve, PG and shorter postoperative period were independently related to worse dumping syndrome. CONCLUSIONS: Dumping syndromes were most common after TGRY and least common after PPG and LR among the various gastrectomy procedures. Type of gastrectomy and several clinical factors were related to the intensity of dumping syndrome. PGSAS-45 could offer a useful tool for evaluating dumping syndrome after gastrectomy. PMID- 26682544 TI - Successful heart transplantation after prolonged cardiac arrest and extracorporeal life support in organ donor-a case report. AB - BACKGROUND: Although heart transplantation is a successful therapy for patients suffering from end-stage heart failure, the therapeutic is limited by the lack of organs. Donor cardiac arrest is a classic hindrance to heart retrieval as it raises issues on post-transplant outcomes. CASE PRESENTATION: The present case reports a successful heart transplantation after prolonged donor cardiac arrest (total lowflow time of 95 minutes) due to anaphylactic shock necessitating extracorporeal life support. We further provide an overview of the current evidence and outcomes of heart transplantation in cases of donor cardiac arrest. CONCLUSION: Providing that donor and recipient criteria are respected, donor cardiac arrest does not seem to be an adverse predictor in heart transplantation. PMID- 26682543 TI - S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers. AB - This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against. PMID- 26682542 TI - Integrative genomic analysis reveals functional diversification of APOBEC gene family in breast cancer. AB - BACKGROUND: The human APOBEC protein family plays critical but distinct roles in host defense. Recent studies revealed that APOBECs mediate C-to-T mutagenesis in multiple cancers, including breast cancer. It is still unclear whether APOBEC gene family shows functional diversification involved in cancer mutagenesis. RESULTS: We performed an integrated analysis to characterize the functional diversification of APOBEC gene family associated with breast cancer mutagenesis relative to estrogen receptor (ER) status. Among the APOBEC family, we found that both APOBEC3B and APOBEC3C mRNA levels were significantly higher in estrogen receptor negative (ER-) subtype compared with estrogen receptor positive (ER+) subtype (P < 2.2 * 10(-16) and P < 3.1 * 10(-5), respectively). Epigenomic data further reflected the distinct chromatin states of APOBEC3B and APOBEC3C relative to ER status. Notably, we observed the significantly positive correlation between the APOBEC3B-mediated mutagenesis and APOBEC3B expression levels in ER+ cancers but not in ER- cancers. In contrast, we discovered the negative correlation of APOBEC3C mRNA levels with base-substitution mutations in ER- tumors. Meanwhile, we observed that breast cancers in carriers of germline deletion of APOBEC3B gene harbor similar mutation patterns, but higher mutation rates in the TCW motif (W corresponds to A or T) than cancers in non-carriers, indicating additional factors may also induce carcinogenic mutagenesis. CONCLUSIONS: These results suggest that functional potential of APOBEC3B and APOBEC3C involved in cancer mutagenesis is associated with ER status. PMID- 26682545 TI - Gut Dysbiosis in Patients with Anorexia Nervosa. AB - Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients. PMID- 26682546 TI - Feeding Behavior of a Crab According to Cheliped Number. AB - Cheliped loss through autotomy is a common reflexive response in decapod crustaceans. Cheliped loss has direct and indirect effects on feeding behavior which can affect population dynamics and the role of species in the community. In this study, we assessed the impact of autotomy (0, 1, or 2 cheliped loss) on feeding behavior in the crab Pachygrapsus transversus, an omnivorous and abundant species that inhabits subtropical intertidal rocky shores along the South Atlantic Ocean. Autotomy altered crab feeding patterns and foraging behavior; however, the time spent foraging on animal prey or algae was not affected. These results indicate a plasticity of feeding behavior in P. transversus, allowing them to maintain feeding when injured. PMID- 26682547 TI - The SOS Response Master Regulator LexA Is Associated with Sporulation, Motility and Biofilm Formation in Clostridium difficile. AB - The LexA regulated SOS network is a bacterial response to DNA damage of metabolic or environmental origin. In Clostridium difficile, a nosocomial pathogen causing a range of intestinal diseases, the in-silico deduced LexA network included the core SOS genes involved in the DNA repair and genes involved in various other biological functions that vary among different ribotypes. Here we describe the construction and characterization of a lexA ClosTron mutant in C. difficile R20291 strain. The mutation of lexA caused inhibition of cell division resulting in a filamentous phenotype. The lexA mutant also showed decreased sporulation, a reduction in swimming motility, greater sensitivity to metronidazole, and increased biofilm formation. Changes in the regulation of toxin A, but not toxin B, were observed in the lexA mutant in the presence of sub-inhibitory concentrations of levofloxacin. C. difficile LexA is, therefore, not only a regulator of DNA damage but also controls many biological functions associated with virulence. PMID- 26682548 TI - What matters in type 2 diabetes mellitus oral treatment? A discrete choice experiment to evaluate patient preferences. AB - AIMS: The aim of this empirical study is to evaluate patient preferences for different characteristics of oral type 2 diabetes mellitus (T2DM) treatment. As T2DM treatment requires strict adherence, patient needs and preferences should be taken into consideration. METHODS: Based on a qualitative and quantitative analysis, a discrete choice experiment (DCE) was applied to identify patient preferences. Apart from six identical attributes (adjustment of glycated hemoglobin [HbA1c], prevention of hypoglycemia, risk of genital infection, risk of gastrointestinal problems, risk of urinary tract infection, and weight change), one continuous variable of either "additional healthy life years" (AHY) or "additional costs" attribute (AC) was included. The DCE was conducted using a fractional factorial design, and the statistical data analysis used random effect logit models. RESULTS: In total, N = 626 (N = 318 AHY + N = 308 AC) T2DM patients participated in the survey. The estimation revealed a clear dominance for prevention of hypoglycemia (coefficient 0.937) and adjustment of HbA1c (coefficient 0.541). The attributes, "additional healthy life years" (coefficient 0.458) or "additional costs" (coefficient 0.420), were in the middle rank and both of significant impact. The side effects, risk of genital infection (coefficient 0.301), risk of gastrointestinal problems (coefficient 0.296), and risk of urinary tract infection (coefficient 0.241) followed in this respective order. Possible weight change (coefficient 0.047) was of less importance (last rank) to the patients in this evaluation. CONCLUSIONS: These survey results demonstrate how much a (hypothetical) T2DM oral treatment characteristic affects the treatment decision. The preference data can be used for risk-benefit assessment, cost-benefit assessment, and the establishment of patient-oriented evidence. Understanding how patients perceive and value different aspects of diabetes oral treatment is vital to the optimal design and evaluation of treatment options. The present results can be an additional source of information for design, assessment, and decision in T2DM treatment regimes. As such, more effective and efficient care of patients can be achieved, thereby increasing adherence. PMID- 26682549 TI - Modeling the costs and long-term health benefits of screening the general population for risks of cardiovascular disease: a review of methods used in the literature. AB - BACKGROUND: Strategies for screening and intervening to reduce the risk of cardiovascular disease (CVD) in primary care settings need to be assessed in terms of both their costs and long-term health effects. We undertook a literature review to investigate the methodologies used. METHODS: In a framework of developing a new health-economic model for evaluating different screening strategies for primary prevention of CVD in Europe (EPIC-CVD project), we identified seven key modeling issues and reviewed papers published between 2000 and 2013 to assess how they were addressed. RESULTS: We found 13 relevant health economic modeling studies of screening to prevent CVD in primary care. The models varied in their degree of complexity, with between two and 33 health states. Programmes that screen the whole population by a fixed cut-off (e.g., predicted 10-year CVD risk >20 %) identify predominantly elderly people, who may not be those most likely to benefit from long-term treatment. Uncertainty and model validation were generally poorly addressed. Few studies considered the disutility of taking drugs in otherwise healthy individuals or the budget impact of the programme. CONCLUSIONS: Model validation, incorporation of parameter uncertainty, and sensitivity analyses for assumptions made are all important components of model building and reporting, and deserve more attention. Complex models may not necessarily give more accurate predictions. Availability of a large enough source dataset to reliably estimate all relevant input parameters is crucial for achieving credible results. Decision criteria should consider budget impact and the medicalization of the population as well as cost-effectiveness thresholds. PMID- 26682550 TI - Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology. AB - BACKGROUND/AIMS: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). METHODS: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. RESULTS: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. CONCLUSION: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology. PMID- 26682551 TI - Resilience of Self-Organised and Top-Down Planned Cities--A Case Study on London and Beijing Street Networks. AB - The success or failure of the street network depends on its reliability. In this article, using resilience analysis, the author studies how the shape and appearance of street networks in self-organised and top-down planned cities influences urban transport. Considering London and Beijing as proxies for self organised and top-down planned cities, the structural properties of London and Beijing networks first are investigated based on their primal and dual representations of planar graphs. The robustness of street networks then is evaluated in primal space and dual space by deactivating road links under random and intentional attack scenarios. The results show that the reliability of London street network differs from that of Beijing, which seems to rely more on its architecture and connectivity. It is found that top-down planned Beijing with its higher average degree in the dual space and assortativity in the primal space is more robust than self-organised London using the measures of maximum and second largest cluster size and network efficiency. The article offers an insight, from a network perspective, into the reliability of street patterns in self-organised and top-down planned city systems. PMID- 26682553 TI - Career development: a focused plan or serendipity? PMID- 26682554 TI - Coding for biopsies, shave removals, and excisions. AB - Biopsies, shave removals, and excisions are basic procedures that dermatologists routinely perform to diagnose disease, relieve symptoms, and to treat cancers. From a coding perspective, these 3 procedures are characterized differently based on the intent and depth of the removal. Specialized biopsy codes are available for certain anatomic sites, and soft-tissue excision codes can be used in lieu of standard skin excision codes for tumors that are confined to the subcutis and below. PMID- 26682555 TI - Status report from the American Acne & Rosacea Society on medical management of acne in adult women, part 2: topical therapies. AB - In part 1 of this 3-part series, an overview of the epidemiology, visible patterns, and important considerations for clinical and laboratory evaluation of acne vulgaris (AV) in adult women was provided. Proper selection and integration of skin care products is important in the management of AV in this patient population. Part 2 of this series includes a discussion of over-the-counter and prescription topical therapies for adult women with AV. A summary of key randomized controlled trials also is provided. Further well-designed studies are needed, as data on the use of topical agents in this subpopulation are limited. PMID- 26682556 TI - Cerebral cavernous malformations associated with cutaneous angiokeratomas and hemangiomas. AB - We report the case of a 66-year-old man with adult-onset seizures and multiple cerebral cavernous malformations who developed numerous eruptive cutaneous angiokeratomas on the legs, scrotum, abdomen, and back as well as lobular and cavernous hemangiomas on the arms. Genetic analysis demonstrated a mutation in the KRIT1, ankyrin repeat containing gene (also known as CCM1). PMID- 26682552 TI - Phosphorylation of the Synaptonemal Complex Protein Zip1 Regulates the Crossover/Noncrossover Decision during Yeast Meiosis. AB - Interhomolog crossovers promote proper chromosome segregation during meiosis and are formed by the regulated repair of programmed double-strand breaks. This regulation requires components of the synaptonemal complex (SC), a proteinaceous structure formed between homologous chromosomes. In yeast, SC formation requires the "ZMM" genes, which encode a functionally diverse set of proteins, including the transverse filament protein, Zip1. In wild-type meiosis, Zmm proteins promote the biased resolution of recombination intermediates into crossovers that are distributed throughout the genome by interference. In contrast, noncrossovers are formed primarily through synthesis-dependent strand annealing mediated by the Sgs1 helicase. This work identifies a conserved region on the C terminus of Zip1 (called Zip1 4S), whose phosphorylation is required for the ZMM pathway of crossover formation. Zip1 4S phosphorylation is promoted both by double-strand breaks (DSBs) and the meiosis-specific kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulation of interhomolog crossover formation, as well as interhomolog bias. Failure to phosphorylate Zip1 4S results in meiotic prophase arrest, specifically in the absence of SGS1. This gain of function meiotic arrest phenotype is suppressed by spo11Delta, suggesting that it is due to unrepaired breaks triggering the meiotic recombination checkpoint. Epistasis experiments combining deletions of individual ZMM genes with sgs1-md zip1-4A indicate that Zip1 4S phosphorylation functions prior to the other ZMMs. These results suggest that phosphorylation of Zip1 at DSBs commits those breaks to repair via the ZMM pathway and provides a mechanism by which the crossover/noncrossover decision can be dynamically regulated during yeast meiosis. PMID- 26682557 TI - A novel cream formulation containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05% for treatment of epidermal melasma. AB - Epidermal melasma is a common hyperpigmentation disorder that can be challenging to treat. Although current treatment options for melasma are limited, topical skin-lightening preparations have widely been used as alternatives to hydroquinone. In this prospective, single-arm, open-label study, treatment of epidermal melasma with a novel cream formulation containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05% was associated with reductions in Melasma Area and Severity Index (MASI) scores as well as total melasma surface area as measured by medical imaging software. Treatment outcomes including tolerance and safety profiles as well as patient satisfaction and product appreciation showed this novel cosmetic compound may be valuable in the treatment of epidermal melasma. PMID- 26682558 TI - What is your diagnosis? Tinea corporis. PMID- 26682559 TI - Desmoplastic melanoma. PMID- 26682560 TI - Recurrent omphalitis secondary to a hair-containing umbilical foreign body. PMID- 26682561 TI - Linear bluish-black papules on the shoulder. PMID- 26682562 TI - Transient reactive papulotranslucent acrokeratoderma: a report of 3 cases showing excellent response to topical calcipotriene. PMID- 26682563 TI - Fillers in dermatology: from past to present. AB - Injectable fillers were introduced in dermatology as a method for reconstructing facial deformities and restoring the aging face. Although fillers have become a popular option among cosmetic patients, clinical experience has shown that fillers must be used with caution, as complications can occur. This article provides a brief review of the history of filler agents currently available for soft tissue augmentation. Although no single filler is ideal for all patients, indications, and situations, residents should be aware of the properties and characteristics that make each product unique. PMID- 26682564 TI - Factors associated with missed dermatology appointments. PMID- 26682565 TI - Sessile pink plaque on the lower back. PMID- 26682566 TI - Disseminated cutaneous infection with Mycobacterium chelonae in a renal transplant recipient. AB - Mycobacterium chelonae belongs to a rapidly growing group of nontuberculous mycobacteria (NTM). These organisms are environmental saprophytes that can cause infection in humans. Nontuberculous mycobacteria infections have been described in immunosuppressed patients (eg, in the setting of AIDS or immunotherapy following solid organ transplantation) as well as in immunocompetent patients with certain predisposing factors (eg, recent history of a traumatic wound, recent drug injections, impaired cell-mediated immunity). Due to the increasing prevalence of immune deficiency disorders as well as the rising number of cosmetic procedures performed on healthy individuals, NTM may become a frequent cause of serious morbidity, causing chronic infections of the skin, soft tissue, and lungs. We report a case of M chelonae infection in a 61-year-old woman who was receiving immunosuppressive therapy following renal transplantation 6 years prior to presentation. It is important for clinicians to consider NTM in the differential diagnosis for patients who present with chronic skin or soft tissue infections. PMID- 26682567 TI - Introduction to: Endocrinological aspects of andrology-what is new? PMID- 26682568 TI - The role of emotion in patient safety: Are we brave enough to scratch beneath the surface? AB - Healthcare professionals work in emotionally charged settings; yet, little is known about the role of emotion in ensuring safe patient care. This article presents current knowledge in this field, drawing upon psychological approaches and evidence from clinical settings. We explore the emotions that health professionals experience in relation to making a medical error and describe the impact on healthcare professionals and on their professional and patient relationships. We also explore how positive and negative emotions can contribute to clinical decision making and affect responses to clinical situations. Evidence to date suggests that emotion plays an integral role in patient safety. Implications for training, practice and research are discussed in addition to strategies to facilitate health services to understand and respond to the influence of emotion in clinical practice. PMID- 26682569 TI - Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes. AB - AIM: To evaluate the performance of a point-of-care test for detection of matrix metalloproteinase 9 (MMP-9) levels in post-laser-assisted in situ keratomileusis (LASIK) dry eyes. METHODS: A comparative study between patients with mild to moderate post-LASIK dry eyes and age-matched normal subjects was conducted. Ocular surface disease index (OSDI), tear break-up time (TBUT), and tear film MMP 9 and total protein levels were compared between the two groups. A point-of-care test device (RPS InflammaDry, Sarasota, Florida, USA) was utilised to confirm elevated MMP-9 levels in tear film. RESULTS: Fourteen post-LASIK dry eyes and 34 normal eyes were included. There was no significant difference in age and gender between both groups (p>0.175). The OSDI was significantly higher (25.5+/-7.7 vs 7.4+/-2.5; p<0.001) and TBUT levels were significantly lower (5.4+/-0.9 vs 13.5+/ 2.3; p<0.001) in patients with dry eye compared with normal subjects. The tear film MMP-9 levels were 52.7+/-32.5 ng/mL in dry eyes and 4.1+/-2.1 ng/mL in normal eyes (p<0.001). MMP-9 levels were >40 ng/mL in 7/14 (50.0%) post-LASIK dry eyes. The InflammaDry was positive in 8/14 (57.1%) post-LASIK eyes. All positive cases had tear film MMP-9 levels >=38.03 ng/mL. Agreement between InflammaDry and MMP-9 was excellent with Cohen kappa value of 0.857 in post-LASIK dry eyes. CONCLUSIONS: Only half of post-LASIK dry eyes were found to have significant inflammation associated with elevated MMP-9. The OSDI is useful to non specifically identify patients with symptomatic dry eye while the InflammaDry determined which patients with dry eye were associated with significant inflammation that may guide therapeutic management decisions. PMID- 26682570 TI - Concise gene signature for point-of-care classification of tuberculosis. AB - There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real-time PCR analysis, we evaluated the expression profiles from a large panel of genes in TB patients and healthy individuals in an Indian cohort. Classification models were built and validated for their capacity to discriminate samples from TB patients and controls within this cohort and on external independent gene expression datasets. A combination of only four genes distinguished TB patients from healthy individuals in both cross-validations and on separate validation datasets with very high accuracy. An external validation on two distinct cohorts using a real-time PCR setting confirmed the predictive power of this 4-gene tool reaching sensitivity scores of 88% with a specificity of around 75%. Moreover, this gene signature demonstrated good classification power in HIV(+) populations and also between TB and several other pulmonary diseases. Here we present proof of concept that our 4-gene signature and the top classifier genes from our models provide excellent candidates for the development of molecular point-of-care TB diagnosis in endemic areas. PMID- 26682571 TI - The Role of Language Use in Reports of Musculoskeletal Pain Among Hispanic and Non-Hispanic White Adolescents. AB - OBJECTIVE: This study examined the role of English language use in the reported frequency of musculoskeletal pain among Hispanic and non-Hispanic White youth. METHOD: This is a secondary data analysis using a cross-sectional sample of 12,189 Hispanic and non-Hispanic White adolescents recruited for the National Longitudinal Study of Adolescent to Adult Health. Respondents were classified into three groups: (a) English-speaking non-Hispanic Whites, (b) English-speaking Hispanics, and (c) Spanish-speaking Hispanics. RESULTS: After controlling for body mass index and demographic, socioeconomic, and behavioral variables, Spanish speaking Hispanics reported the least frequent musculoskeletal pain ( OR = 0.415, 95% CI [0.361, 0.477]; p < .001), followed by English-speaking Hispanics ( OR = 0.773, 95% CI [0.690, 0.865]; p < .001). CONCLUSION: The experience of musculoskeletal pain is a physiological as well as a cultural phenomenon. IMPLICATIONS FOR PRACTICE: Health care providers should consider the role of language use in reports of pain in Hispanic and non-Hispanic White adolescents. PMID- 26682572 TI - A Fast Hydrogen Sulfide-Releasing Donor Increases the Tumor Response to Radiotherapy. AB - Hydrogen sulfide (H2S) is the last gaseous transmitter identified in mammals, and previous studies have reported disparate conclusions regarding the implication of H2S in cancer progression. In the present study, we hypothesized that sodium hydrosulfide (NaHS), a fast H2S-releasing donor, might interfere with the mitochondrial respiratory chain of tumor cells, increase tumor oxygenation, and potentiate the response to irradiation. Using electron paramagnetic resonance (EPR) oximetry, we found a rapid increase in tumor pO2 after NaHS administration (0.1 mmol/kg) in two human tumor models (breast MDA-MB-231 and cervix SiHa), an effect that was due to a decreased oxygen consumption and an increased tumor perfusion. Tumors irradiated 15 minutes after a single NaHS administration were more sensitive to irradiation compared with those that received irradiation alone (increase in growth delay by 50%). This radiosensitization was due to the oxygen effect, as the increased growth delay was abolished when temporarily clamped tumors were irradiated. In contrast, daily NaHS injection (0.1 mmol/kg/day for 14 days) did not provide any effect on tumor growth in vivo. To understand these paradoxical data, we analyzed the impact of external factors on the cellular response to NaHS. We found that extracellular pH had a dramatic effect on the cell response to NaHS, as the proliferation rate (measured in vitro by BrdU incorporation) was increased at pH = 7.4, but decreased at pH = 6.5. Overall, our study highlights the complex role of environmental components in the response of cancer cells to H2S and suggests a new approach for the use of H2S donors in combination with radiotherapy. PMID- 26682573 TI - Activation of EGFR Bypass Signaling by TGFalpha Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells. AB - Alectinib is a highly selective ALK inhibitor and shows promising efficacy in non small cell lung cancers (NSCLC) harboring the EML4-ALK gene rearrangement. The precise mechanism of acquired resistance to alectinib is not well defined. The purpose of this study was to clarify the mechanism of acquired resistance to alectinib in ALK-translocated lung cancer cells. We established alectinib resistant cells (H3122-AR) from the H3122 NSCLC cell line, harboring the EML4-ALK gene rearrangement, by long-term exposure to alectinib. The mechanism of acquired resistance to alectinib in H3122-AR cells was evaluated by phospho-receptor tyrosine kinase (phospho-RTK) array screening and Western blotting. No mutation of the ALK-TK domain was found. Phospho-RTK array analysis revealed that the phosphorylation level of EGFR was increased in H3122-AR cells compared with H3122. Expression of TGFalpha, one of the EGFR ligands, was significantly increased and knockdown of TGFalpha restored the sensitivity to alectinib in H3122-AR cells. We found combination therapy targeting ALK and EGFR with alectinib and afatinib showed efficacy both in vitro and in a mouse xenograft model. We propose a preclinical rationale to use the combination therapy with alectinib and afatinib in NSCLC that acquired resistance to alectinib by the activation of EGFR bypass signaling. PMID- 26682574 TI - The effects of acute and preventive migraine therapies in a mouse model of chronic migraine. AB - Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine preventive treatments. Methods Migraine therapies were administered to male and female mice for 11 days. On day 3, mice were tested with nitroglycerin every second day for nine days. Basal and nitroglycerin-evoked mechanical hypersensitivity was evaluated using von Frey filaments. Results Chronic intermittent nitroglycerin produced acute hyperalgesia with each administration, and progressive and sustained basal hypersensitivity. The established preventive migraine therapy propranolol effectively blocked the development of acute and chronic nitroglycerin-induced hyperalgesia, while valproate had no effect. Potential migraine-preventive therapies were also tested: Amiloride inhibited nitroglycerin-induced acute and chronic hyperalgesia; while memantine was ineffective. We also tested the acute migraine therapy sumatriptan, which did not alter nitroglycerin-induced hyperalgesia, but instead resulted in acute and chronic hyperalgesia similar to that observed following nitroglycerin administration. Conclusions This study establishes the chronic nitroglycerin model as an additional screening tool to test novel migraine-preventive therapies. PMID- 26682575 TI - How common is normal cerebrospinal fluid pressure in spontaneous intracranial hypotension? AB - Objectives To determine the proportion of patients with spontaneous intracranial hypotension (SIH) who had a cerebrospinal fluid (CSF) pressure >6 cm H2O and to investigate the clinical and imaging variables associated with CSF pressure ( PCSF) in this condition. Methods We retrospectively reviewed 106 patients with SIH. PCSF was measured by lumbar puncture prior to treatment. Clinical and imaging variables - including demographic data, brain imaging results, symptom duration, and abdominal circumference - were collected. Univariate and multivariate analyses were performed to determine the correlation of these variables with PCSF. Results Sixty-one percent of patients had a PCSF between 6 and 20 cm H2O; only 34% had a PCSF <=6 cm H2O. The factors associated with increased PCSF included abdominal circumference ( p < 0.001), symptom duration ( p = 0.015), and the absence of brain magnetic resonance imaging findings of SIH ( p = 0.003). A wide variability in PCSF was observed among all patients, which was not completely accounted for by the variables included in the model. Conclusions Normal CSF pressure is common in patients with SIH; the absence of a low opening pressure should not exclude this condition. Body habitus, symptom duration, and brain imaging are correlated with PCSF measurements, but these factors alone do not entirely explain the wide variability in observed pressures in this condition and this suggests the influence of other factors. PMID- 26682576 TI - Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL): A case report with serial electroencephalography (EEG) recordings.. Is there an association with human herpes virus type 7 (HHV-7) infection? AB - Introduction The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a diagnosis made by exclusion. In the literature, different etiological explanations are proposed for HaNDL, including an immune-mediated reaction after a viral infection. Case description We present a case of a 23-year-old woman with several episodes of transient headache, neurological deficits and cerebrospinal fluid lymphocytosis. All diagnostic criteria for the HaNDL syndrome were fulfilled; however, additional cerebrospinal fluid analysis showed a positive polymerase chain reaction (PCR) for human herpes virus type 7 (HHV-7). Discussion The possible role of a (prodromal) viral infection in the etiology of HaNDL is discussed. Also the role of electroencephalography (EEG) recordings is discussed. Serial EEG recordings showed generalized slowing, frontal intermittent rhythmic delta activity (FIRDA) and symmetric triphasic frontal waves with a dilation lag. PMID- 26682577 TI - Angiostrongylus cantonensis cathepsin B-like protease (Ac-cathB-1) is involved in host gut penetration. AB - Although the global spread of the emerging zoonosis, human angiostrongyliasis, has attracted increasing attention, understanding of specific gene function has been impeded by the inaccessibility of genetic manipulation of the pathogen nematode causing this disease, Angiostrongylus cantonensis. Many parasitic proteases play key roles in host-parasite interactions, but those of A. cantonensis are always expressed as the inactive form in prokaryotic expression systems, thereby impeding functional studies. Hence, a lentiviral system that drives secreted expression of target genes fused to a Myc-His tag was used to obtain recombinant Ac-cathB-1 with biological activity. Although this class of proteases was always reported to function in nutrition and immune evasion in parasitic nematodes, recombinant Ac-cathB-1 was capable of hydrolysis of fibronectin and laminin as well as the extracellular matrix of IEC-6 monolayer, so that the intercellular space of the IEC-6 monolayer increased 5.15 times as compared to the control, while the shape of the adherent cells partly rounded up. This suggests a probable role for this protease in intestinal epithelial penetration. The inhibition of Ac-cathB-1 enzymatic activity with antiserum partly suppressed larval penetration ability in the isolated intestine. Thus, an effective system for heterologous expression of parasite proteases is presented for studying gene function in A. cantonensis; and Ac-cathB-1 was related to larval penetration ability in the host small intestine. PMID- 26682578 TI - Comparison between the stripping technique and the combined excisional/ablative technique for the treatment of bilateral ovarian endometriomas: a multicentre RCT. AB - STUDY QUESTION: Is the combined excisional/ablative technique for the treatment of ovarian endometriomas better than the traditional stripping technique in terms of recurrence rate? SUMMARY ANSWER: There is no evidence that the combined excisional/ablative technique is better than the traditional stripping technique, as similar recurrence rates were observed for the two techniques. WHAT IS KNOWN ALREADY: The stripping technique is associated with better results compared with ablative, non-excisional techniques for the treatment of ovarian endometriomas. Excisional techniques, such as stripping, have, however, been associated with reduced ovarian reserve as evaluated with anti-Mullerian hormone, and surgical techniques that better preserve the ovarian reserve are needed. STUDY DESIGN, SIZE, DURATION: A prospective, multicentre, randomized blinded clinical trial was carried out on 51 patients with bilateral endometriomas larger than 3 cm. For each patient, serving as her own control, one ovary was randomized to the stripping technique and the contralateral to the combined excisional/ablative technique. Patients were enrolled between January 2013 and April 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients of reproductive age with pelvic pain and/or infertility affected by bilateral endometriomas larger than 3 cm were included (n = 51). The patients underwent laparoscopic removal of endometriomas with two different surgical techniques performed at either side after random assignment: complete removal by stripping on one side versus the combined technique, consisting of partial excisional cystectomy followed by completion with ablative surgery using bipolar coagulation, on the other side. Post-operative follow-up was performed at 1, 3 and 6 months after surgery for the evaluation of endometrioma recurrence (primary outcome) and of antral follicle count (AFC) and ovarian volumes (OVs) to assess ovarian reserve (secondary outcome). MAIN RESULTS AND THE ROLE OF CHANCE: Recurrence rates were 5.9% for the stripping technique versus 2.0% for the combined technique (odds ratio 3.00; 95% confidence interval: 0.24-157.5; P = 0.62). AFC in the ovaries treated with the stripping technique did not differ significantly from AFC in ovaries treated with the combined technique at all follow-up visits, whereas OV was significantly lower after the combined technique at the 6-month follow-up visit (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: A major limitation of this study is the small sample size and particularly for ovarian reserve, the secondary outcome, for which no formal sample size calculation was performed. The lower-than-expected recurrence rates in the present series may be related to the shorter follow-up in our study compared with most studies in the literature. Further studies with larger sample sizes and longer follow-up are needed to confirm the findings of this study. The combined technique using CO2 laser energy instead of bipolar coagulation should also be evaluated. WIDER IMPLICATIONS OF THE FINDINGS: The traditional excisional technique, i.e. the stripping technique, should still be considered the gold standard approach for the surgical treatment of endometriomas. STUDY FUNDING/COMPETING INTERESTS: No commercial funding was received. The authors report no relevant conflict of interest. TRIAL REGISTRATION NUMBER: ANZCTR number ACTRN12614000653662. TRIAL REGISTRATION DATE: 23 June 2014. DATE OF FIRST PATIENT'S ENROLMENT: 1 January 2013. PMID- 26682579 TI - A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels. AB - STUDY QUESTION: Could drugs targeting ATP-sensitive K(+) (K(ATP)) channels prevent any spontaneous increase in intracellular Ca(2+) that may occur in human metaphase II (MII) oocytes under in vitro conditions? SUMMARY ANSWER: Pinacidil, a K(ATP) channel opener, and glibenclamide, a K(ATP) channel blocker, prevent a spontaneous increase in intracellular Ca(2+) in human MII oocytes. WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca(2+) homeostasis is crucial for cell wellbeing and increased intracellular Ca(2+) levels is a well-established indicator of cell stress. STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca(2+) levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP. PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean +/- SD) age 34.1 +/- 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca(2+)-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca(2+) monitoring was 80.4 +/- 2.1 h. MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca(2+) increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 +/- 11.8 AU (AU = arbitrary units; n = 23) to 91.8 +/- 14.0 AU (n = 19; P < 0.001) after 2 h of monitoring. Pinacidil (100 uM) inhibited this increase in Ca(2+) (85.3 +/- 12.3 AU at the beginning of the experiment, 81.7 +/- 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 uM) also inhibited the increase in Ca(2+) (74.7 +/- 10.6 AU at the beginning and 71.8 +/- 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca(2+) that was inhibited by glibenclamide (100 uM; n = 9) but not by pinacidil (100 uM; n = 5). LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca(2+) in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 +/- 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca(2+) homeostasis and, furthermore, the altered Ca(2+) homeostasis might have been associated solely with the protracted incubation. WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca(2+), which can be counteracted by drugs targeting K(ATP) channels. As Ca(2+) homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that K(ATP) channel openers and blockers should be tested as drugs for improving success rates of ART. STUDY FUNDING/COMPETING INTERESTS: University of Dundee, MRC (MR/K013343/1, MR/012492/1), NHS Tayside. Funding NHS fellowship (Dr Sarah Martins da Silva), NHS Scotland. The authors declare no conflicts of interest. PMID- 26682580 TI - 'How to count sperm properly': checklist for acceptability of studies based on human semen analysis. AB - STUDY QUESTION: Can a tool be developed for authors, reviewers and editors of the ESHRE Journals to improve the quality of published studies which rely on semen analysis data? SUMMARY ANSWER: A basic checklist for authors, reviewers and editors has been developed and is presented. WHAT IS KNOWN ALREADY: Laboratory work which includes semen analysis is burdened by a lack of standardization. This has significant negative effects on the quality of scientific and epidemiological studies, potential misclassification of patients and the potential to impair clinical treatments/diagnoses that rely on accurate semen quality information. Robust methods are available to reduce laboratory error in semen analysis, inducing adherence to World Health Organization techniques, participation in an external quality control scheme and appropriate training of laboratory personnel. However, journals have not had appropriate systems to assess if these methods have been used. STUDY DESIGN, SIZE, DURATION: After discussion at a series of Associate Editor Meetings of the ESHRE Journals the authors of the present text were asked to propose a tool for authors, reviewers and editors of the ESHRE Journals to ensure a high quality assessment of submitted manuscripts which rely on semen analysis data, including a detailed verification of the relevance and the quality of the methods used. PARTICIPANTS/MATERIALS, SETTING, METHODS: N/A. MAIN RESULTS AND THE ROLE OF CHANCE: A basic checklist for authors, reviewers and editors is presented. The checklist contains key points which should be considered by authors when designing studies and which provides essential information for when the submitted manuscript is evaluated. For published articles the answers in the checklist are suitable to be available as supplementary data, which will also reduce the space necessary for technical details in the printed article. LIMITATIONS, REASONS FOR CAUTION: Guidelines such as these should not be used uncritically. It is therefore important that submitting authors, in situations where their study does not comply with the basic requirements for semen analysis, not only explain all methodological deviations but also declare the level of uncertainty in their analyses and how it complies with, or might confound, the aims of the study. WIDER IMPLICATIONS OF THE FINDINGS: The fundamental importance of appropriate and robust methodology to facilitate advances in scientific understanding and patient management and treatment, is now accepted as being paramount. Use of the semen analysis checklist should be part of this process, and when completed and signed by the corresponding author at the time of submitting a manuscript should result in greater transparency, and ultimately uniformity. It is hoped that this initiative will pave the way for wider adoption of the methodology/reporting by other biomedical, epidemiological and scientific journals, and ultimately become the standard of practice for papers reporting semen analysis results obtained in laboratory and clinical andrology. Systems to assist referees, authors and editors to present high quality findings should have a significant impact on the field of reproductive medicine. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this work. The authors have no competing interests in relation to the present publication and checklist. TRIAL REGISTRATION NUMBER: N/A. PMID- 26682581 TI - Protective Effects of Curcumin on Intestinal Damage in Cholestatic Rats. AB - BACKGROUND: The aim of this study was to evaluate the possible protective effects of curcumin on oxidative stress, cell proliferation, and apoptosis in the rat intestinal mucosa after bile duct ligation (BDL). METHODS: A total of 18 male Sprague Dawley rats were divided into three groups: sham control, BDL and BDL+curcumin; each group contain six animals. The rats in the curcumin-treated group were given curcumin (100 mg/kg) once a day orally for 14 days, starting 3 days prior to BDL operation. Following 14 days of treatment, all the animals were decapitated and intestinal tissues samples obtained for biochemical and histopathological investigation. RESULTS: Curcumin treatment was found to significantly lower elevated tissue malondialdehyde levels and myeloperoxidase activity, and to raise reduced glutathione levels in intestinal tissues samples. BDL caused severe histopathological injury, including shortening of the villi, loss of villous epithelium, multiple erosions, inflammatory cell infiltration, necrosis, and hemorrhage into the intestinal wall. Curcumin treatment significantly attenuated the severity of intestinal injury, with inhibition of BDL-induced apoptosis and cell proliferation. CONCLUSION: Curcumin treatment has a protective effect against intestinal damage induced by BDL. The ability of curcumin treatment is to inhibit BDL-induced oxidative stress, apoptosis, and cell proliferation. PMID- 26682583 TI - Synergistic effects of Arbuscular mycorrhizal fungi and plant growth promoting rhizobacteria in bioremediation of iron contaminated soils. AB - Three Arbuscular mycorrhizal fungi (AMF) from Glomus, Acaulospora and Scutellospora, and four plant growth promoting rhizobacteria (PGPR) isolates related to genera Streptomyces, Azotobacter, Pseudomonas and Paenibacillus were found to be effective in phytoremediation of Fe(3+) contaminated soil where Pennisetum glaucum and Sorghum bicolor were growing as host plants. Co inoculation of AMF and PGPR showed better results in comparison to either, AMF and PGPR under pot conditions. Both AMF and PGPR were able to produce siderophores. AMF and PGPR associated to P. glaucum and S. bicolor plants increased the extent of iron absorption. AMF and PGPR combination exhibited superior (p < 0.01) phytoremediation efficiency with P. glaucum compared to S. bicolor. These findings warrant further investigations of these synergistic interactions and large-scale in situ studies for bioremediation of iron contaminated soils. PMID- 26682582 TI - Training opioid addiction treatment providers to adopt contingency management: A prospective pilot trial of a comprehensive implementation science approach. AB - BACKGROUND: Few prospective studies have evaluated theory-driven approaches to the implementation of evidence-based opioid treatment. This study compared the effectiveness of an implementation model (Science to Service Laboratory; SSL) to training as usual (TAU) in promoting the adoption of contingency management across a multisite opioid addiction treatment program. We also examined whether the SSL affected putative mediators of contingency management adoption (perceived innovation characteristics and organizational readiness to change). METHODS: Sixty treatment providers (39 SSL, 21 TAU) from 15 geographically diverse satellite clinics (7 SSL, 8 TAU) participated in the 12-month study. Both conditions received didactic contingency management training and those in the predetermined experimental region received 9 months of SSL-enhanced training. Contingency management adoption was monitored biweekly, whereas putative mediators were measured at baseline, 3 months, and 12 months. RESULTS: Relative to providers in the TAU region, treatment providers in the SSL region had comparable likelihood of contingency management adoption in the first 20 weeks of the study, and then significantly higher likelihood of adoption (odds ratios = 2.4-13.5) for the remainder of the study. SSL providers also reported higher levels of one perceived innovation characteristic (Observability) and one aspect of organizational readiness to change (Adequacy of Training Resources), although there was no evidence that the SSL affected these putative mediators over time. CONCLUSIONS: Results of this study indicate that a fully powered randomized trial of the SSL is warranted. Considerations for a future evaluation are discussed. PMID- 26682597 TI - Computed tomography parameters for atlantooccipital dislocation in adult patients: the occipital condyle-C1 interval. AB - OBJECT: Atlantooccipital dislocation (AOD) in adults cannot be diagnosed with adequate specificity and sensitivity using only CT or plain radiography, and the spine literature offers no guidelines. In children, the most sensitive and specific radiographic measurement for the diagnosis of AOD is the CT-based occipital condyle-C1 interval (CCI). The goal of the current study was to identify the normal CCI in healthy adults and compare it with the CCI in adults with AOD to establish a highly sensitive and specific cutoff value for the neuroimaging diagnosis of AOD. METHODS: A total of 81 patients, 59 without AOD and 22 with AOD, were included in this study. Measurements obtained from thin slice CT scans of the craniovertebral joint to assess atlantooccipital dislocation included the CCI, condylar sum, the Wholey and Harris intervals, Powers and Sun ratios, Wackenheim line, and Lee X-lines. RESULTS: The group of patients without AOD included 30 men (50.8%) and 29 women (49.2%) with a mean age of 42.4 +/- 16 years (range 19-87 years). The group of patients with AOD included 10 men (45.5%) and 12 women (54.5%) with a mean age of 38.2 +/- 9.7 years (range 20-56 years). Interrater reliabilities within a 95% CI were all greater than 0.98 for CCI measurements. A total of 1296 measurements of the CCI were made in 81 patients. The mean CCI for non-AOD patients was 0.89 +/- 0.12 mm, the single largest CCI measurement was 1.4 mm, and the largest mean for either right or left CCI was 1.2 mm. The mean condylar sum was 1.8 +/- 0.2 mm, and the largest condylar sum value was 2.2 mm. Linear regression with age predicted an increase in CCI of 0.001 mm/year (p < 0.05). The mean CCI in AOD patients was 3.35 +/- 0.18 mm (range 1.5 mm-6.4 mm). The shortest single CCI measurements in the AOD patients were 1.1 mm and 1.2 mm. The mean condylar sum for all 22 AOD patients was 6.7 +/- 2.7 mm and the shortest condylar sums were 3.0 mm. Cutoff values for AOD were set at 1.5 mm for the CCI and 3.0 mm for the condylar sum, both with a sensitivity of 1 and false-negative rate of 0. Sensitivity for the Powers, Wholey, Harris, Sun, Wackenheim, and Lee criteria were determined to be 0.55, 0.46, 0.27, 0.23, 0.41, and 0.41, respectively. CONCLUSIONS: The CCI is shorter in adult patients as opposed to the pediatric population. The revised CCI (1.5 mm) and condylar sum (3.0 mm) cutoff values have the highest sensitivity and specificity for the diagnosis of AOD in the adult population. PMID- 26682598 TI - Creating reproducible thoracolumbar burst fractures in human specimens: an in vitro experiment. AB - OBJECT: The treatment of traumatic burst fractures unaccompanied by neurological impairment remains controversial and ranges from conservative management to 360 degrees fusion. Because of the heterogeneity of fracture types, classification systems, and treatment options, comparative biomechanical studies might help to improve our knowledge. The aim of the current study was to create a standardized fracture model to investigate burst fractures in a multisegmental setting. METHODS: A total of 28 thoracolumbar fresh-frozen human cadaveric spines were used. The spines were dissected into segments (T11-L3). The T-11 and L-3 vertebral bodies were embedded in Technovit 3040 (cold-curing resin for surface testing and impressions). To simulate high energy, a metallic drop tower was designed. Stress risers were used to ensure comparable fractures. CT scans were acquired before and after fracture. All fractures were classified using the AO/OTA classification. RESULTS: The preparation and embedding of the spine segments worked well. No repositioning or second embedding of the specimen, even after fracture, was required. It was possible to create single burst fractures at the L-1 level in all 28 spine segments. Among the 28 fractures there were 16 incomplete burst fractures (Type A3.1), 8 burst-split fractures (Type A3.2), and 4 complete burst fractures (Type A3.3). The differences before and after fracture for stiffness and for anterior, posterior, and central heights were all significant (p < 0.05). CONCLUSIONS: The ability to create reproducible burst fractures of a single vertebral body in a thoracolumbar spine segment may serve as a basis for future biomechanical studies that will provide better understanding of mechanical properties or fixation techniques. PMID- 26682599 TI - Spinal arteriovenous shunts: accuracy of shunt detection, localization, and subtype discrimination using spinal magnetic resonance angiography and manual contrast injection using a syringe. AB - OBJECT: The object of this study was to evaluate the accuracy of fast 3D contrast enhanced spinal MR angiography (MRA) using a manual syringe contrast injection technique for detecting and evaluating spinal arteriovenous shunts (AVSs). METHODS: This was a retrospective study of 15 patients and 20 spinal MRA and catheter angiography studies. The accuracy of using spinal MRA to detect spinal AVS, localize shunts, and discriminate the subtype and dominant arterial feeder of the AVS were studied. RESULTS: There were 14 pretherapeutic and 6 posttherapeutic follow-up spinal MRA and catheter spinal angiography studies. The spinal AVS was demonstrated in 17 of 20 studies. Spinal MRA demonstrated 100% sensitivity for detecting spinal AVS with no false-negative results. A 97% accuracy rate for AVS subtype discrimination and shunt level localization was achieved using this study's diagnostic criteria. The detection of the dominant arterial feeder was limited to 9 of these 17 cases (53%). CONCLUSIONS: The fast 3D contrast-enhanced MRA technique performed using manual syringe contrast injection can detect the presence of a spinal AVS, locate the shunt level, and discriminate AVS subtype in most cases, but is limited when detecting small arterial feeders. PMID- 26682600 TI - Treatment of subaxial cervical facet dislocations. PMID- 26682602 TI - The lateral extracavitary approach to the thoracolumbar spine: a case series and systematic review. AB - OBJECT: Since its introduction in 1976, the lateral extracavitary approach (LECA) has been used to access ventral and ventrolateral pathology affecting the thoracolumbar spine. Reporting of outcomes and complications has been inconsistent. A case series and systematic review are presented to summarize the available data. METHODS: A retrospective review of medical records was performed, which identified 65 consecutive patients who underwent LECA for the treatment of thoracolumbar spine and spinal cord pathology. Cases were divided according to the presenting pathology. Neurological outcomes and complications were detailed. In addition, a systematic review of outcomes and complications in patients treated with the LECA as reported in the literature was completed. RESULTS: Sixty five patients underwent the LECA to the spine for the treatment of thoracic spine and spinal cord pathology. The most common indication for surgery was thoracic disc herniation (23/65, 35.4%). Neurological outcomes were excellent: 69.2% improved, 29.2% experienced no change, and 1.5% were worse. Two patients (3.1%) experienced a complication. The systematic review revealed comparable neurological outcomes (74.9% improved) but a notably higher complication rate (32.2%). CONCLUSIONS: The LECA provides dorsal and unilateral ventrolateral access to and exposure of the thoracolumbar spine and spinal cord while allowing for posterior instrumentation through the same incision. Although excellent neurological results can be expected, the risk of pulmonary complications should be considered. PMID- 26682601 TI - Mobile spine chordoma: results of 166 patients from the AOSpine Knowledge Forum Tumor database. AB - OBJECT: A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS: Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS: A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96-16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS: EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine. PMID- 26682603 TI - Patterns of epidural progression following postoperative spine stereotactic body radiotherapy: implications for clinical target volume delineation. AB - OBJECT: The authors performed a pattern-of-failure analysis, with a focus on epidural disease progression, in patients treated with postoperative spine stereotactic body radiotherapy (SBRT). METHODS: Of the 70 patients with 75 spinal metastases (cases) treated with postoperative spine SBRT, there were 26 cases of local disease recurrence and 25 cases with a component of epidural disease progression. Twenty-four of the 25 cases had preoperative epidural disease with subsequent epidural disease progression, and this cohort was the focus of this epidural-specific pattern-of-failure investigation. Preoperative, postoperative, and follow-up MRI scans were reviewed, and epidural disease was characterized based on location according to a system in which the vertebral anatomy is divided into 6 sectors, with the anterior compartment comprising Sectors 1, 2, and 6, and the posterior compartment comprising Sectors 3, 4, and 5. RESULTS: Patterns of epidural progression are reported specifically for the 24 cases with preoperative epidural disease and subsequent epidural progression. Epidural disease progression within the posterior compartment was observed to be significantly lower in those with preoperative epidural disease confined to the anterior compartment than in those with preoperative epidural disease involving both anterior and posterior compartments (56% vs. 93%, respectively; p = 0.047). In a high proportion of patients with epidural disease progression, treatment failure was found in the anterior compartment, including both those with preoperative epidural disease confined to the anterior compartment and those with preoperative epidural disease involving both anterior and posterior compartments (100% vs. 73%, respectively). When epidural disease was confined to the anterior compartment on the preoperative and postoperative MRIs, no epidural disease progression was observed in Sector 4, which is the most posterior sector. Postoperative epidural disease characteristics alone were not predictive of the pattern of epidural treatment failure. CONCLUSIONS: Reviewing the extent of epidural disease on preoperative MRI is imperative when planning postoperative SBRT. When epidural disease is confined to the anterior epidural sectors pre- and postoperatively, covering the entire epidural space circumferentially with a prophylactic "donut" distribution may not be needed. PMID- 26682604 TI - Fracture of fusion mass after hardware removal in patients with high sagittal imbalance. AB - OBJECT: As spinal fusions become more common and more complex, so do the sequelae of these procedures, some of which remain poorly understood. The authors report on a series of patients who underwent removal of hardware after CT-proven solid fusion, confirmed by intraoperative findings. These patients later developed a spontaneous fracture of the fusion mass that was not associated with trauma. A series of such patients has not previously been described in the literature. METHODS: An unfunded, retrospective review of the surgical logs of 3 fellowship trained spine surgeons yielded 7 patients who suffered a fracture of a fusion mass after hardware removal. Adult patients from the West Virginia University Department of Orthopaedics who underwent hardware removal in the setting of adjacent-segment disease (ASD), and subsequently experienced fracture of the fusion mass through the uninstrumented segment, were studied. The medical records and radiological studies of these patients were examined for patient demographics and comorbidities, initial indication for surgery, total number of surgeries, timeline of fracture occurrence, risk factors for fracture, as well as sagittal imbalance. RESULTS: All 7 patients underwent hardware removal in conjunction with an extension of fusion for ASD. All had CT-proven solid fusion of their previously fused segments, which was confirmed intraoperatively. All patients had previously undergone multiple operations for a variety of indications, 4 patients were smokers, and 3 patients had osteoporosis. Spontaneous fracture of the fusion mass occurred in all patients and was not due to trauma. These fractures occurred 4 months to 4 years after hardware removal. All patients had significant sagittal imbalance of 13-15 cm. The fracture level was L-5 in 6 of the 7 patients, which was the first uninstrumented level caudal to the newly placed hardware in all 6 of these patients. Six patients underwent surgery due to this fracture. CONCLUSIONS: The authors present a case series of 7 patients who underwent surgery for ASD after a remote fusion. These patients later developed a fracture of the fusion mass after hardware removal from their previously successfully fused segment. All patients had a high sagittal imbalance and had previously undergone multiple spinal operations. The development of a spontaneous fracture of the fusion mass may be related to sagittal imbalance. Consideration should be given to reimplanting hardware for these patients, even across good fusions, to prevent spontaneous fracture of these areas if the sagittal imbalance is not corrected. PMID- 26682605 TI - FACTORIAL VALIDITY OF THE KOREAN VERSION OF THE EXERCISE DEPENDENCE SCALE REVISED. AB - This study evaluated the psychometric properties of the Korean version of the 21 item Exercise Dependence Scale-Revised (EDS-R). The EDS-R was designed to measure the multidimensional aspects of exercise dependence symptoms such as withdrawal, continuance, tolerance, lack of control, reductions, time, and intention. Although the EDS-R has demonstrated sound psychometric properties, it has only been validated in Western samples. Cross-cultural validations of the instrument may increase the knowledge of exercise dependence. Therefore, this study aimed to contribute to the file by investigating the validity and utility of the construct of the EDS-R, using a non-Western sample. 402 adult participants who were over 18 years of age and who reported exercising at least once a week were asked to complete the EDS-R. The results from factor analyses supported that the seven factor model of exercise dependence symptoms showed an adequate fit for both men and women. The EDS-R scores differentiated between samples, with varying amounts of exercise; 15.4% of the sample was classified as being at risk for exercise dependence. In sum, the results indicated that the EDS-R is a psychometrically reliable assessment tool for exercise dependence symptoms in Korea. PMID- 26682606 TI - CONTROLLING ABSOLUTE FREQUENCY OF FEEDBACK IN A SELF-CONTROLLED SITUATION ENHANCES MOTOR LEARNING. AB - The guidance hypothesis suggested that excessive extrinsic feedback facilitates motor performance but blocks the processing of intrinsic information. The present study tested the tenet of guidance hypothesis in self-controlled feedback by controlling the feedback frequency. The motor learning effect of limiting absolute feedback frequency was examined. Thirty-six participants (25 men, 11 women; M age=25.1 yr., SD=2.2) practiced a hand-grip force control task on a dynamometer by the non-dominant hand with varying amounts of feedback. They were randomly assigned to: (a) Self-controlled, (b) Yoked with self-controlled, and (c) Limited self-controlled conditions. In acquisition, two-way analysis of variance indicated significantly lower absolute error in both the yoked and limited self-controlled groups than the self-controlled group. The effect size of absolute error between trials with feedback and without feedback in the limited self-controlled condition was larger than that of the self-controlled condition. In the retention and transfer tests, the Limited self-controlled feedback group had significantly lower absolute error than the other two groups. The results indicated an increased motor learning effect of limiting absolute frequency of feedback in the self-controlled condition. PMID- 26682607 TI - EFFECT OF SEX, AGE, AND BMI ON THE DEVELOPMENT OF LOCOMOTOR SKILLS AND OBJECT CONTROL SKILLS AMONG PRESCHOOL CHILDREN. AB - Purposive sampling was used to recruit 1,200 preschoolers between the ages of three and seven from 12 preschools throughout Taiwan in order to examine locomotor skills, object control skills, and fundamental motor skills with respect to sex, age, and body mass index (BMI). Fundamental motor skills were measured using the TGMD-2. Only age had a significant influence on locomotor skills, object control skills, and fundamental motor skills; sex had a small influence on object control skills, and BMI had a very limited influence on all three categories. The difference from previous studies related to BMI may be due to the different items included in the various tests, the number of trials conducted, and ways in which BMI was categorized. PMID- 26682608 TI - PROMOTING GROSS MOTOR SKILLS IN TODDLERS: THE ACTIVE BEGINNINGS PILOT CLUSTER RANDOMIZED TRIAL. AB - This study examined the feasibility, acceptability, and potential efficacy of a gross motor skill program for toddlers. An 8-wk. skills program in which children practiced three skills was implemented for 10 min. daily in two randomly designated childcare centers. Two other centers served as the control group. Recruitment and retention rates were collected for feasibility. Data on professional development, children's participation, program duration, and appropriateness of the lessons were collected for acceptability, and the Test of Gross Motor Development-2 and Get Skilled, Get Active (total of 28 points) were used to look at the potential efficacy. The participants were 60 toddlers (M age=2.5 yr., SD=0.4; n=29 boys), and the retention rate was 95%. Overall participation was 76%, and educators rated 98% of the lessons as appropriate. Compared with the control group, the intervention group showed significantly greater improvements in motor skills (p<.05, Cohen's d=1.13). This study shows that a brief intervention, which is easy to integrate on a daily basis in childcare settings, can improve motor skills among toddlers. PMID- 26682609 TI - THE EFFECT OF CHRONOTYPE ON PSYCHOPHYSIOLOGICAL RESPONSES DURING AEROBIC SELF PACED EXERCISES. AB - It was hypothesized that an individual's chronotype might influence the response to physical activity at a given time of day. This study aimed to analyze the psychophysiological responses during a walking task at different times of day in individuals with different chronotypes. 46 students (M age=24.8 yr., SD=7.2) filled in the Morningness-Eveningness Questionnaire to determine chronotypes. Heart rate, walking time, and the rating of perceived exertion (RPE) were measured during two self-paced walking sessions: one in the morning (08:30) and one in the afternoon (15:30). A multivariate analysis of variance found a significant interaction between chronotype and time of day. The post hoc analysis showed a significant difference for RPE in the morning session, with evening types reporing a higher RPE compared with the morning types. The chronotype and the time of day when a physical task is undertaken can influence the RPE response, although it might not influence physiological or performance parameters. This has to be taken into account, because it can affect test reliability as well as possibly have a negative influence on the affective responses to a given task. PMID- 26682610 TI - CREATIVITY OF PRESCHOOL AND ELEMENTARY SCHOOL TEACHERS AND THEIR STUDENTS. AB - Although creativity provides a considerable number of advantages, many teachers have direct and indirect prejudices against creative students since they may display distracting and disruptive behaviors toward teachers and classmates. To determine how teachers' creativity affects their students' creative development, 90 preschool and elementary school teachers and 90 pupils were assessed for creative thinking. The children's sex was not correlated with creativity scores. There were small, significant relationships between various measures of preschool teachers' and students' creativity. PMID- 26682611 TI - PLAYERS' PERCEPTIONS OF HOME ADVANTAGE IN THE AUSTRALIAN RUGBY LEAGUE COMPETITION. AB - This study was designed to pilot a survey to explore players' perception of home advantage in a rugby league. Twenty-seven players from one team with an identified home advantage believed a home advantage existed as a result of their home crowd (52%), family and friends' support (41%), normal travel (45%) and sleeping arrangements (37%), home weather conditions (48%), and familiarity with playing amenities (37%). However, the players were less definite about influences while playing away from home. The current sample of players identified differing influences, highlighting individual variations in perceived determinants. Individual interviews or focus groups will be required for further exploration. PMID- 26682612 TI - Facile Construction of pH- and Redox-Responsive Micelles from a Biodegradable Poly(beta-hydroxyl amine) for Drug Delivery. AB - Here we demonstrate a type of pH and reduction dual-sensitive biodegradable micelles, which were self-assembled by a cationic polymer in an aqueous solution. Due to tumor cells or tissues showing low pH and high reduction concentration, these micelles possessed specific tumor targetability and maximal drug-release controllability inside tumor cells upon changes in physical and chemical environments, but presented good stability at physiological conditions. CCK-8 assay showed that the DOX-loaded micelles had a similar cytotoxicity for MCF-7 tumor cells as free DOX, and blank micelles had a very low cytotoxicity to the cells. Fluorescent microscopy observation revealed that the drug-loaded micelles could be quickly internalized by endosomes to inhibit cancer cell growth. These results indicated these biodegradable micelles, as a novel and effective pH- and redox-responsive nanocarrier, have a potential to improve drug delivery and enhance the antitumor efficacy. PMID- 26682613 TI - Ab initio study of the enantio-selective magnetic-field-induced second harmonic generation in chiral molecules. AB - We present a systematic ab initio study of enantio-selective magnetic-field induced second harmonic generation (MFISHG) on a set of chiral systems ((l) alanine, (l)-arginine and (l)-cysteine; 3,4-dehydro-(l)-proline; (S)-alpha phellandrene; (R,S)- and (S,S)-cystine disulphide; N-(4-nitrophenyl)-(S) prolinol, N-(4-(2-nitrovinyl)-phenyl)-(S)-prolinol, N-(4-tricyanovinyl-phenyl) (S)-prolinol, (R)-BINOL, (S)-BINAM and 6-(M)-helicene). The needed electronic frequency dependent cubic response calculations are performed within a density functional theory (DFT) approach. A study of the dependence of the property on the choice of electron correlation, on one-electron basis set extension and on the choice of magnetic gauge origin is carried out on a prototype system (twisted oxygen peroxide). The magnetic gauge dependence analysis is extended also to the molecules of the set. An attempt to analyze the structure-property relationships is also made, based on the results obtained for biphenyl (in a frozen twisted conformation), for prolinol and for some of their derivatives. The strength of the effect is discussed, in order to establish its measurability with a proposed experimental setup. PMID- 26682614 TI - Genetic Characterization of Toxoplasma gondii Isolates from Pigs in Jilin Province, Northeastern China. AB - Toxoplasma gondii is prevalent in humans and animals worldwide. The present study aimed to determine the genetic diversity of T. gondii isolates from pigs in Jilin province, northeastern China. A total of 100 DNA samples were extracted from the hilar lymph nodes of slaughtered pigs, and 9 (9.0%, 95% confidence interval: 3.4 14.6%) were detected positive for T. gondii B1 gene by a nested polymerase chain reaction (PCR). The positive DNA samples were typed at 11 genetic markers, including 10 nuclear loci (SAG1, 5'-SAG2, and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, and PK1) and an apicoplast locus (Apico) using the multilocus PCR-restriction fragment length polymorphism technology. Only three isolates were completely typed at all loci, showing that they all belonged to the clonal type I. One isolate was typed at five loci, including 5' +3'-SAG2, SAG2, SAG3, GRA6, and L358, revealing the possible clonal type I. This is the first report of the genetic characterization of T. gondii isolates in pigs in Jilin province, northeastern China, which has implications for better understanding the population structure of T. gondii infection in China. PMID- 26682615 TI - Relapse of Kaposi's Sarcoma and HHV-8 viremia in an HIV-infected patient switching from protease inhibitor to integrase inhibitor-based antiretroviral therapy. AB - Combination antiretroviral therapy (cART) reduced the incidence of Kaposi's Sarcoma (KS), mainly mediated by the suppression of HIV replication and the recovery of the immune system. The effect of specific classes of antiretrovirals on KS remains unclear. However, both in vitro and clinical studies provided evidences that protease inhibitors (PI) can inhibit Human Herpesvirus 8 (HHV-8) replication and reduce KS risk and progression. Moreover, relapses of KS in HIV infected patients switching from a PI to a non-nucleoside reverse transcriptase inhibitor-based cART have been reported. We describe here the case of a patient who experienced a relapse of KS and a rebound of HHV-8 viremia two months after switching from a PI to an integrase inhibitor-based cART. PMID- 26682616 TI - Diagnostic value of "absent" pattern in contrast-enhanced ultrasound for the differentiation of thyroid nodules. AB - OBJECTIVES: Our study sought to investigate the unique diagnostic value of "absent" pattern in contrast-enhanced ultrasound (CEUS) for the differentiation of solid thyroid nodules, also, to analyze corresponding characteristics of B scan ultrasound (US) and real-time elastography (RTE). METHODS: A total of 96 patients enrolled in our study underwent conventional US, RTE and CEUS before fine needle aspiration (FNA) or surgery. Thyroid nodules with the same "absent" pattern of contrast-enhancement were evaluated on the basis of different ultrasound features in B-scan US and RTE. Then accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of thyroid cancer were investigated respectively. RESULTS: Among the five B-scan US features, nodular border obscurity was most predictive of malignancy (accuracy 84.4%, sensitivity 75.0%, specificity 84.8%, p < 0.05). Nevertheless, none of other ultrasound features including RTE was significantly different between benign and malignant thyroid nodules (p > 0.05). Besides, both echohomogeneity and RTE had a high sensitivity of 100%. CONCLUSIONS: Combined with medical history, our study allows to identify a specific role for "absent" pattern of CEUS in the differentiation of thyroid nodules with suspicious ultrasound features in conventional B-scan US and RTE. PMID- 26682617 TI - Triterpenoic Acids from Apple Pomace Enhance the Activity of the Endothelial Nitric Oxide Synthase (eNOS). AB - Pomace is an easy-accessible raw material for the isolation of fruit-derived compounds. Fruit consumption is associated with health-promoting effects, such as the prevention of cardiovascular disease. Increased vascular nitric oxide (NO) bioavailability, for example, due to an enhanced endothelial nitric oxide synthase (eNOS) activity, could be one molecular mechanism mediating this effect. To identify compounds from apple (Malus domestica Borkh.) pomace that have the potential to amplify NO bioavailability via eNOS activation, a bioassay-guided fractionation of the methanol/water (70:30) extract has been performed using the (14)C-L-arginine to (14)C-L-citrulline conversion assay (ACCA) in the human endothelium-derived cell line EA.hy926. Phytochemical characterization of the active fractions was performed using the spectrophotometric assessment of the total phenolic content, as well as TLC, HPLC-DAD-ELSD, and HPLC-MS analyses. Eleven triterpenoic acids, of which one is a newly discovered compound, were identified as the main constituents in the most active fraction, accompanied by only minor contents of phenolic compounds. When tested individually, none of the tested compounds exhibited significant eNOS activation. Nevertheless, cell stimulation with the reconstituted compound mixture restored eNOS activation, validating the potential of apple pomace as a source of bioactive components. PMID- 26682618 TI - Active clearance technology to maintain chest tube patency: Practical, innovative, unproven. PMID- 26682619 TI - Acting on a rare event. PMID- 26682620 TI - Fixed versus dynamic left ventricular outflow tract obstruction: Res ipsa loquitur. PMID- 26682621 TI - Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard--neither Minotaur nor Midas. PMID- 26682622 TI - Challenges in modelling nanoparticles for drug delivery. AB - Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond based drug delivery platforms as an exemplar. PMID- 26682623 TI - Efficient system modeling for a small animal PET scanner with tapered DOI detectors. AB - A prototype small animal positron emission tomography (PET) scanner for mouse brain imaging has been developed at UC Davis. The new scanner uses tapered detector arrays with depth of interaction (DOI) measurement. In this paper, we present an efficient system model for the tapered PET scanner using matrix factorization and a virtual scanner geometry. The factored system matrix mainly consists of two components: a sinogram blurring matrix and a geometrical matrix. The geometric matrix is based on a virtual scanner geometry. The sinogram blurring matrix is estimated by matrix factorization. We investigate the performance of different virtual scanner geometries. Both simulation study and real data experiments are performed in the fully 3D mode to study the image quality under different system models. The results indicate that the proposed matrix factorization can maintain image quality while substantially reduce the image reconstruction time and system matrix storage cost. The proposed method can be also applied to other PET scanners with DOI measurement. PMID- 26682625 TI - Phenotypic variability and heritability of the cephalic region of Caiman latirostris. AB - The study of the cephalic shape of crocodilian is relevant in the fields of ecology, systematics, evolution, and conservation. Therefore, the integration of geometric analysis within quantitative genetics allows the evaluation of the inheritable shape components. In this study, the dorsal cephalic region of 210 Caiman latirostris hatchlings was analyzed from seven populations in Santa Fe, Argentina, to detect intra-, and inter-population phenotypic variability, and to determine the heritability of biological shape and size, using newly available geometric morphometric tools. The principal component analysis showed two configurations of cephalic shape that could be related to sexual dimorphism. In the canonical variate analysis, Procrustes distances between groups indicated that there are differences in shape among populations. Furthermore, the method of partial least squares indicated a covariation between cephalic shape and environmental variables. Regarding to CS of the skull we found significant differences among populations, moreover the partial least squares was also significant. Estimates of the heritability of shape and size were high, indicating that the components of these features are susceptible to the selection. PMID- 26682626 TI - [Pathological complete response: A predictive survival factor after neoadjuvant chemotherapy in lung cancer]. AB - The phase III trials of adjuvant and neoadjuvant chemotherapy showed a 5 % increase survival but the clinical research in this area is difficult because the duration of the trials with overall survival as primary end point is around 10years. To shorten the duration of these studies, the use of surrogate end points such as disease-free survival or relapse-free survival is possible, but does not significantly reduce the duration of studies. Several studies in and outside the lung cancer showed histological complete response or the percentage of viable tumor cells after chemotherapy could be correlated with survival and thus become an interesting alternative criterion. If this is verified, clinical studies of preoperative chemotherapy should be shortened which would allow patients faster access to innovative treatment in the perioperative situation. PMID- 26682628 TI - Definitions of fitness in age-structured populations: Comparison in the haploid case. AB - Fisher's (1930) Fundamental Theorem of Natural Selection (FTNS), and in particular the development of an explicit age-structured version of the theorem, is of everlasting interest. In a recent paper, Grafen (2015a) argues that Fisher regarded his theorem as justifying individual rather than population fitness maximization. The argument relies on a new definition of fitness in age structured populations in terms of individual birth and death rates and age specific reproductive values in agreement with a principle of neutrality. The latter are frequency-dependent and defined without reference to genetic variation. In the same paper, it is shown that the rate of increase in the mean of the breeding values of fitness weighted by the reproductive values, but keeping the breeding values constant as in Price (1972) is equal to the additive genetic variance in fitness. Therefore, this partial change is obtained by keeping constant not only the genotypic birth and death rates but also the mean age-specific birth and death rates from which the age-specific reproductive values are defined. In this paper we reaffirm that the Malthusian parameter which measures the relative rate of increase or decrease in reproductive value of each genotype in a continuous-time age-structured population is the definition of fitness used in Fisher's (1930) FTNS. This is shown by considering an age structured asexual haploid population with constant age-specific birth and death (or survival) parameters for each type. Although the original statement of the FTNS is for a diploid population, this simplified haploid model allows us to address the definition of fitness meant in this theorem without the complexities and effects of a changing genic environment. In this simplified framework, the rate of change in mean fitness in continuous time is expected to be exactly equal to the genetic variance in fitness (or to the genetic variance in fitness divided by the mean fitness in discrete time), which can be seen as a generalized growth rate theorem. This theorem is shown to hold with the Malthusian parameter used as the definition of fitness. Moreover, in the same framework, it is shown that a discrete-time version of Grafen's definition may lead to a decrease in mean fitness. In the limit of weak selection with the unit of time proportional to the inverse of the intensity of selection, however, this definition predicts the right population dynamics in agreement with the growth-rate theorem. This clarifies the domain of application of the new definition, at least as far as population dynamics is concerned, and reconciles the new definition with the original one. PMID- 26682627 TI - How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. AB - Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme's displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations-a possible signature of quantum entanglement-may be explained by such a mechanism. PMID- 26682629 TI - Motor-cognitive dual-task training improves local dynamic stability of normal walking in older individuals. AB - BACKGROUND: Extreme levels of gait variability and local dynamic stability of walking are associated with risk of falling and reduced executive functions. However, it is not sufficiently investigated how gait variability and local dynamic stability of human walking develop in the course of a motor-cognitive intervention. As dancing implies high demands on (and therewith trains) executive functioning and motor control, it might increase local dynamic stability or reduce gait variability. METHODS: 32 older healthy participants were randomly assigned to either a health-related exercise group (age: mean=68.33 years, standard deviation=3.17 years; BMI: mean=27.46, standard deviation=2.94; female/male: 10/6) or a dancing group (age: mean=66.73 years, standard deviation=3.33 years; BMI: mean=26.02, standard deviation=3.55; female/male: 11/5). Based on angular velocity data of trunk kinematics, local dynamic stability and stride-to-stride variability in level overground walking were assessed prior to and after the specific intervention. The data were analysed by a blinded observer using two-way repeated measures ANOVAs. Based on one-way ANOVAs, time and group effects were determined. FINDINGS: Regarding the variability of trunk movements, no interaction effect was observed (F 1,30=0.506, P=.482; eta2=0.017). For local dynamic stability of trunk movements, an interaction effect in favour of the dancing group was observed (F 1,30=5,436; P=.026; eta2=0.146). INTERPRETATION: Our data indicate that a dancing programme (which combines cognitive and motor efforts) might increase local dynamic stability in older people. PMID- 26682630 TI - Persons with unilateral transfemoral amputation experience larger spinal loads during level-ground walking compared to able-bodied individuals. AB - BACKGROUND: Persons with lower limb amputation walk with increased and asymmetric trunk motion; a characteristic that is likely to impose distinct demands on trunk muscles to maintain equilibrium and stability of the spine. However, trunk muscle responses to such changes in net mechanical demands, and the resultant effects on spinal loads, have yet to be determined in this population. METHODS: Building on a prior study, trunk and pelvic kinematics collected during level-ground walking from 40 males (20 with unilateral transfemoral amputation and 20 matched controls) were used as inputs to a kinematics-driven, nonlinear finite element model of the lower back to estimate forces in 10 global (attached to thorax) and 46 local (attached to lumbar vertebrae) trunk muscles, as well as compression, lateral, and antero-posterior shear forces at all spinal levels. FINDINGS: Trunk muscle force and spinal load maxima corresponded with heel strike and toe off events, and among persons with amputation, were respectively 10-40% and 17-95% larger during intact vs. prosthetic stance, as well as 6-80% and 26-60% larger during intact stance relative to controls. INTERPRETATION: During gait, larger spinal loads with transfemoral amputation appear to be the result of a complex pattern of trunk muscle recruitment, particularly involving co-activation of antagonistic muscles during intact limb stance; a period when these individuals are confident and likely to use the trunk to assist with forward progression. Given the repetitive nature of walking, repeated exposure to such elevated loading likely increases the risk for low back pain in this population. PMID- 26682632 TI - Severe Pediatric Bronchomalacia. PMID- 26682631 TI - The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB 231 in vitro. AB - Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF 7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 MUM) in MDA MB-231 cells. DS (5.76 MUM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 +/- 5% in the presence of 5.76 MUM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer. PMID- 26682633 TI - Metal-Free Chemoselective Oxidative Dehomologation or Direct Oxidation of Alcohols: Implication for Biomass Conversion. AB - A transition metal-free, chemoselective reaction was performed using the sodium tert-butoxide-oxygen (NaO(t) Bu-O2 ) system, resulting in either oxidative dehomologation or direct oxidation of alcohols. In particular, the newly developed protocol may be used to predict the major product formed, which depends on alkyl chain length of the alcohols and reaction conditions. The rational mechanism of this transformation was also demonstrated by performing an (18) O isotopic labelling experiment. This protocol presents a straightforward method for biomass conversion of a lignin model compound to phenol and benzoic acid. PMID- 26682634 TI - Immunohistochemical analysis of O6-methylguanine-DNA methyltransferase (MGMT) protein expression as prognostic marker in glioblastoma patients treated with radiation therapy with concomitant and adjuvant Temozolomide. AB - BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) protein expression using immunohistochemical analysis was proposed as a prognostic marker for patients with newly diagnosed glioblastoma (GBM) treated with radiation therapy with concurrent and adjuvant Temozolomide (TMZ). METHODS: From April 2012 to October 2014, 73 patients with newly diagnosed GBM, MGMT protein expression were analyzed in formalin-fixed, paraffin-embedded tumor specimens. Patients received the radiation therapy plus concomitant and adjuvant TMZ chemotherapy. RESULTS: For the whole cohort, the median overall survival (OS) was 15 months, and the progression-free survival was 10 months. Patients who had low MGMT protein expression (?15%) had a significantly improved OS and PFS compared with patients who had high MGMT expression (17.0 months vs 14 months; P value .006) and (15.0 months vs 10 months; P value .016) respectively. The age and extent of tumor resection were the strongest clinical predictors of outcome. In multivariate Cox models MGMT protein expression, extent of tumor resection and age were identified as independent prognostic factors. CONCLUSIONS: MGMT expression was identified as positive prognostic factor in patients with newly diagnosed glioblastoma who underwent surgical resection followed by adjuvant radiotherapy and concomitant oral TMZ chemotherapy (the Stupp protocol). PMID- 26682635 TI - Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade. AB - Endometrial cancer is the most common invasive gynecological malignancy. Flotillin-1 is an integral membrane protein and estrogen responsive gene. Flotillin-1 expression and localization in human endometrial cancers grades 1-3 was investigated using real-time RT-PCR and immunohistochemistry. Flotillin-1 mRNA levels were unchanged in endometrial cancer versus benign endometrium. Flotillin-1 protein was significantly reduced in the epithelial compartment with increasing tumor grade, although levels increased in the tumor stroma across grades. We have identified a novel factor in human endometrial cancer and observed a shift in epithelial to stromal localization with increasing tumor grade in women. PMID- 26682636 TI - Healthcare-associated pneumonia: Can we salvage anything from the wreckage? PMID- 26682637 TI - Invasive diagnostic techniques in idiopathic interstitial pneumonias. AB - Fibrosing interstitial lung diseases (f-ILDs) represent a heterogeneous group of disorders in which the aetiology may be identified or, not infrequently, remain unknown. Establishing a correct diagnosis of a distinct f-ILD requires a multidisciplinary approach, integrating clinical profile, physiological and laboratory data, radiological appearance and, when appropriate, histological findings. Surgical lung biopsy is still considered the most important diagnostic tool as it is able to provide lung samples large enough for identification of complex patterns such as usual interstitial pneumonitis (UIP) and nonspecific interstitial pneumonitis. However, this procedure is accompanied by significant morbidity and mortality. Bronchoalveolar lavage is still a popular diagnostic tool allowing identification of alternative diagnoses in patients with suspected idiopathic pulmonary fibrosis (IPF) when an increase in lymphocytes is detected. Conventional transbronchial lung biopsy has a very low sensitivity in detecting the UIP pattern and its role in this clinical-radiological context is marginal. The introduction of less invasive methods such as transbronchial cryobiopsy show great promise to clinical practice as they can be used to obtain samples large enough to morphologically support a diagnosis of IPF or other idiopathic interstitial pneumonias, along with fewer complications. Recent advances in the field suggest that less invasive methods of lung sampling, without significant side effects, in combination with other diagnostic methods could replace the need for surgical lung biopsy in the future. Indeed, these new multidisciplinary procedures may become the main diagnostic work-up method for patients with suspected idiopathic interstitial pneumonia. PMID- 26682639 TI - Erratum. PMID- 26682638 TI - Predictors of Pseudomonas and methicillin-resistant Staphylococcus aureus in hospitalized patients with healthcare-associated pneumonia. AB - BACKGROUND AND OBJECTIVE: Patients with healthcare-associated pneumonia (HCAP) are at high risk of infection with multidrug-resistant (MDR) pathogens. Factors discriminating infection with MDR Gram-negative (MDR-GN) organism from infection with methicillin-resistant Staphylococcus aureus (MRSA) are not well understood and patients are often treated for both organisms. This study was performed to determine risk factors predicting pneumonia due to Pseudomonas versus MRSA. METHODS: Veterans age >=65 hospitalized with HCAP between 2002 and 2012 were identified from the Veterans Affairs administrative databases. Patients were identified with Pseudomonas pneumonia, MRSA pneumonia or neither according to the International Classification of Diseases, 9th Revision, Clinical Modification codes. We assessed unadjusted and adjusted associations of patient characteristics and HCAP due to Pseudomonas or MRSA. RESULTS: Of the 61,651 patients with HCAP, 1156 (1.9%) were diagnosed with Pseudomonas pneumonia, 641 (1.0%) with MRSA pneumonia and 59,854 (97.1%) with neither. MRSA pneumonia was positively associated with male gender, age >74, diabetes, chronic obstructive pulmonary disease (COPD), recent nursing home or hospital stay, recent exposure to fluoroquinolone or antibiotics treating Gram-positive organisms, and severe pneumonia. MRSA pneumonia was negatively associated with complicated diabetes. Pseudomonas pneumonia was positively associated with recent hospital stay, immunocompromise, COPD, hemiplegia, recent exposure to inhaled corticosteroids, beta-lactam/cephalosporin/carbapenem antibiotics, antibiotics against Gram positive organisms, 'other antibiotics' and severe pneumonia. Pseudomonas pneumonia was negatively associated with age >84, higher socioeconomic status, drug abuse and diabetes. CONCLUSIONS: Patient characteristics may assist in identifying patients at risk for HCAP due to Pseudomonas or MRSA. PMID- 26682640 TI - Erratum. PMID- 26682641 TI - 1,1,1,3,3,3-Hexafluoroisopropanol as a Remarkable Medium for Atroposelective Sulfoxide-Directed Fujiwara-Moritani Reaction with Acrylates and Styrenes. AB - Axially chiral biaryls are ubiquitous structural motifs of biologically active molecules and privileged ligands for asymmetric catalysis. Their properties are due to their configurationally stable axis, and therefore, the control of their absolute configuration is essential. Efficient access to atropo-enantioenriched biaryl moieties through asymmetric direct C-H activation, by using enantiopure sulfoxide as both the directing group (DG) and chiral auxiliary, is reported. The stereoselective oxidative Heck reactions are performed in high yields and with excellent atropo-stereoselectivities. The pivotal role of 1,1,1,3,3,3 hexafluoropropanol (HFIP) solvent, which enables a drastic increase in yield and stereoselectivity of this transformation, is evidenced and investigated. Finally, the synthetic usefulness of the herein disclosed transformation is showcased because the traceless character of the sulfoxide DG allows straightforward conversions of the newly accessed, atropopure sulfoxide-biaryls into several differently substituted axially chiral scaffolds. PMID- 26682642 TI - The Essential Role of Spermidine in Growth of Agrobacterium tumefaciens Is Determined by the 1,3-Diaminopropane Moiety. AB - The ubiquitous polyamine spermidine is indispensable for eukaryotic growth and cell proliferation. A conserved vital function of spermidine across eukaryotes is conferred by its aminobutyl group that is transferred to a single lysine in translation factor eIF5A to form the essential hypusine post-translational modification required for cellular translation. In direct contrast, although spermidine is absolutely essential for growth of alpha-proteobacterial plant pathogen Agrobacterium tumefaciens, we have found, by employing a suite of natural polyamines and synthetic methylated spermidine analogues together with spermidine biosynthetic mutants, that it is solely the 1,3-diaminopropane moiety of spermidine that is required for growth. Indeed, any polyamine containing an intact terminal 1,3-diaminopropane moiety can replace spermidine for growth, including the simple diamine 1,3-diaminopropane itself, a paradigm shift in understanding polyamine function in bacteria. We have identified for the first time a spermidine retroconversion activity in bacteria, producing diamine putrescine from triamine spermidine; however, exogenously supplied tetraamine spermine is resistant to retroconversion. When spermidine levels are pharmacologically decreased, synthesis of spermine from spermidine is induced via the same biosynthetic enzymes, carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase that produce spermidine from putrescine, the first identification of a spermine biosynthetic pathway in bacteria. This also suggests that spermidine represses spermine biosynthesis, but when spermidine levels decrease, it is then converted by carboxyspermidine dehydrogenase and decarboxylase enzymes to spermine, which is resistant to retroconversion and constitutes a sequestered pool of protected 1,3-diaminopropane modules required for growth. We also identify an efficient N-acetylspermidine deacetylase activity, indicative of a sophisticated bacterial polyamine homeostasis system. PMID- 26682643 TI - Amphiphilic Diblock Terpolymer PMAgala-b-P(MAA-co-MAChol)s with Attached Galactose and Cholesterol Grafts and Their Intracellular pH-Responsive Doxorubicin Delivery. AB - In this work, a series of diblock terpolymer poly(6-O-methacryloyl-D galactopyranose)-b-poly(methacrylic acid-co-6-cholesteryloxy hexyl methacrylate) amphiphiles bearing attached galactose and cholesterol grafts denoted as the PMAgala-b-P(MAA-co-MAChol)s were designed and prepared, and these terpolymer amphiphiles were further exploited as a platform for intracellular doxorubicin (DOX) delivery. First, employing a sequential RAFT strategy with preliminarily synthesized poly(6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose) (PMAIpGP) macro-RAFT initiator and a successive trifluoroacetic acid (TFA) mediated deprotection, a series of amphiphilic diblock terpolymer PMAgala-b-P(MAA co-MAChol)s were prepared, and were further characterized by NMR, Fourier transform infrared spectrometer (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and a dynamic contact angle testing instrument (DCAT). In aqueous media, spontaneous micellization of the synthesized diblock terpolymer amphiphiles were continuously examined by critical micellization concentration assay, dynamic light scattering (DLS), and transmission electron microscopy (TEM), and the efficacies of DOX loading by these copolymer micelles were investigated along with the complexed nanoparticle stability. Furthermore, in vitro DOX release of the drug-loaded terpolymer micelles were studied at 37 degrees C in buffer under various pH conditions, and cell toxicities of as-synthesized diblock amphiphiles were examined by MTT assay. Finally, with H1299 cells, intracellular DOX delivery and localization by the block amphiphile vectors were investigated by invert fluorescence microscopy. As a result, it was revealed that the random copolymerization of MAA and MAChol comonomers in the second block limited the formation of cholesterol liquid crystal phase and enhanced DOX loading efficiency and complex nanoparticle stability, that ionic interactions between the DOX and MAA comonomer could be exploited to trigger efficient DOX release under acidic condition, and that the diblock terpolymer micellular vector could alter the DOX trafficking in cells. Hence, these suggest the pH-sensitive PMAgala-b-P(MAA-co-MAChol)s might be further exploited as a smart nanoplatform toward efficient antitumor drug delivery. PMID- 26682644 TI - The association of air pollution and depressed mood in 70,928 individuals from four European cohorts. AB - BACKGROUND: Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. METHODS: Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. RESULTS: A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 MUg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 MUg/m(3) increase in NO2). CONCLUSIONS: Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood. PMID- 26682645 TI - Association of Interleukin-10-1082A/G Polymorphism with Idiopathic Recurrent Miscarriage: A Systematic Review and Meta-Analysis. AB - PROBLEM: This systematic review and meta-analysis aimed to synthesize and assess the correlation between the interleukin-10 (IL-10)-1082A/G polymorphism and idiopathic recurrent miscarriage (IRM) using relevant studies. METHOD OF STUDY: Five electronic databases (Cochrane Library of Systematic Reviews, PubMed, EMBASE, Web of Science, and Google Scholar) were comprehensively searched up to August 2015. Data were extracted independently by two members of our team. RESULTS: The meta-analysis of 13 eligible studies suggested a recessive effect of the G allele (-1082A/G polymorphism) for IRM risk. CONCLUSIONS: The pooled evidence demonstrated that the GG genotype increased IRM risk. PMID- 26682646 TI - Radiological follow-up results of untreated anterior disc displacement without reduction in adults. AB - The aim of this study was to assess the radiographic changes in untreated adults with bilateral anterior disc displacement without reduction. A cohort study was designed to compare the bone changes, effusion, disc configuration, and pseudo disc changes on two magnetic resonance images obtained at least 24 months apart. Twenty-eight patients (22 female, six male) with a mean age of 33.1 years (range 20-57 years) were included. The mean interval between the initial visit and the follow-up visit was 36.2 months. At the initial visit, the frequencies of bone changes, effusion, disc deformation, and pseudo-disc changes were 51.79%, 35.71%, 100%, and 0%, respectively. At follow-up, the frequency of effusion had decreased significantly. The frequency of bone changes had increased significantly to 75%, but newly formed cortical bone was present in five condyles. All discs remained deformed. Pseudo-disc changes were detected in five joints. Over a long period of observation, there was a significant decrease in effusion and a significant increase in bone changes. However, some adaptive changes occurred. PMID- 26682647 TI - Telephone Calls Make a Difference in Home Balance Training Outcomes: A Randomized Trial. AB - BACKGROUND AND PURPOSE: To determine the benefit of a weekly telephone contact on balance control for community-dwelling frail older adults participating in home exercise programs. Falls in frail older adults often lead to hospitalization and sometimes death. Evidence supports the effectiveness of home exercise programs in reducing fall risk in older adults. As well, there is a high cost for the delivery of a home exercise program in a traditional manner. Poor adherence to a home exercise program can limit the expected reduction in fall risk in the older adult population. We hypothesized that a weekly telephone call would improve adherence to a home-exercise program and, therefore, improve outcomes on the Berg Balance Test. METHODS: Seventy-five community-dwelling, frail older adult participants, at risk for falling (mean age: 76 years, range: 64-88 years; 3 women), were randomized in alternating pairs to a Telephone Call or No Telephone Call group. All participants received physical therapy home-exercise programs focused on balance control and were assessed and progressed 4 times over 12 weeks. All participants used an exercise log in which they were asked to record the amount of time and the number of repetitions performed of all daily exercises. The Telephone Call group received an additional 15-minute weekly telephone call with standard questions and encouragement to discuss their program. The primary outcome measure was the Berg Balance Scale. RESULTS: A total of 11 subjects dropped out of the study with 8 from the No Telephone Call group and 3 from the Telephone Call group. For both groups, a significant effect for time was noted, demonstrating that both groups improved significantly in balance control with the home exercise intervention. For the Berg Balance Scale, an interaction occurred whereby the Telephone Call group improved significantly more in balance control than the No Telephone Call group (Telephone Call group = 6.3 points; No Telephone Call group = 3.9 points). CONCLUSIONS: A home exercise program was beneficial to improve the balance of community-dwelling frail older adults. More importantly for health policy consideration, a simple, weekly, telephone call made a significant difference in how much balance improvement was made. Telephone calls are a cost-effective way to provide effective follow-up support for older adults participating in home exercise programs. PMID- 26682648 TI - Artifact free reconstruction with the system matrix approach by overscanning the field-free-point trajectory in magnetic particle imaging. AB - Magnetic particle imaging is a tracer-based imaging method that utilizes the non linear magnetization response of iron-oxide for determining their spatial distribution. The method is based on a sampling scheme where a sensitive spot is moved along a trajectory that captured a predefined field-of-view (FOV). However, particles outside the FOV also contribute to the measurement signal due to their rotation and the non-sharpness of the sensitive spot. In the present work we investigate artifacts that are induced by particles not covered by the FOV and show that the artifacts can be mitigated by using a system matrix that covers not only the region of interest but also a certain area around the FOV. The findings are especially relevant when using a multi-patch acquisition scheme where the boundaries of neighboring patches have to be handled. PMID- 26682649 TI - IPMK: A versatile regulator of nuclear signaling events. AB - Inositol-derived metabolites (e.g., phosphoinositides and inositol polyphosphates) are key second messengers that are essential for controlling a wide range of cellular events. Inositol polyphosphate multikinase (IPMK) exhibits complex catalytic activities that eventually yield water-soluble inositol polyphosphates (e.g., IP4 and IP5) and lipid-bound phosphatidylinositol 3,4,5 trisphosphate. A series of recent studies have suggested that IPMK may be a multifunctional regulator in the nucleus of mammalian cells. In this review, we highlight the novel modes of action of IPMK in transcriptional and epigenetic regulation, and discuss its roles in physiology and disease. PMID- 26682650 TI - Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage. AB - Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 A resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. Structure-guided mutations in vitro and in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance. PMID- 26682651 TI - Evidence for a common evolutionary rate in metazoan transcriptional networks. AB - Genome sequences diverge more rapidly in mammals than in other animal lineages, such as birds or insects. However, the effect of this rapid divergence on transcriptional evolution remains unclear. Recent reports have indicated a faster divergence of transcription factor binding in mammals than in insects, but others found the reverse for mRNA expression. Here, we show that these conflicting interpretations resulted from differing methodologies. We performed an integrated analysis of transcriptional network evolution by examining mRNA expression, transcription factor binding and cis-regulatory motifs across >25 animal species, including mammals, birds and insects. Strikingly, we found that transcriptional networks evolve at a common rate across the three animal lineages. Furthermore, differences in rates of genome divergence were greatly reduced when restricting comparisons to chromatin-accessible sequences. The evolution of transcription is thus decoupled from the global rate of genome sequence evolution, suggesting that a small fraction of the genome regulates transcription. PMID- 26682652 TI - Hippocampal ensemble dynamics timestamp events in long-term memory. AB - The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. PMID- 26682654 TI - Strangers and Strange Lands. PMID- 26682656 TI - Using Skin-to-Skin Contact to Increase Exclusive Breastfeeding at a Military Medical Center. AB - Evidence shows that early formula supplementation leads to early weaning from exclusive breastfeeding. We implemented an evidence-based practice project on skin-to-skin contact (SSC) for healthy term newborns at a large military treatment facility in an effort to decrease formula supplementation in the early postpartum period. Military women face unique challenges when it comes to breastfeeding. SSC in the early postpartum period is an effective intervention to increase exclusive breastfeeding during the hospital stay and foster future positive breastfeeding outcomes. Through this project, staff knowledge of the benefits of SSC to women and newborns improved and the hospital's exclusive breastfeeding rate increased by 20 percent. PMID- 26682653 TI - Increases in core temperature counterbalance effects of haemoconcentration on blood viscosity during prolonged exercise in the heat. AB - NEW FINDINGS: What is the central question of this study? The purpose of the present study was to determine the effects of exercise-induced haemoconcentration and hyperthermia on blood viscosity. What is the main finding and its importance? Exercise-induced haemoconcentration, increased plasma viscosity and increased blood aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell (RBC) deformability (e.g. RBC membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. Previous studies have reported that blood viscosity is significantly increased following exercise. However, these studies measured both pre- and postexercise blood viscosity at 37 degrees C even though core and blood temperatures would be expected to have increased during the exercise. Consequently, the effect of exercise-induced hyperthermia on mitigating change in blood viscosity may have been missed. The purpose of this study was to isolate the effects of exercise induced haemoconcentration and hyperthermia and to determine their combined effects on blood viscosity. Nine subjects performed 2 h of moderate-intensity exercise in the heat (37 degrees C, 40% relative humidity), which resulted in significant increases from pre-exercise values for rectal temperature (from 37.11 +/- 0.35 to 38.76 +/- 0.13 degrees C), haemoconcentration (haematocrit increased from 43.6 +/- 3.6 to 45.6 +/- 3.5%) and dehydration (change in body weight = -3.6 +/- 0.7%). Exercise-induced haemoconcentration significantly (P < 0.05) increased blood viscosity by 9% (from 3.97 to 4.33 cP at 300 s(-1)), whereas exercise induced hyperthermia significantly decreased blood viscosity by 7% (from 3.97 to 3.69 cP at 300 s(-1)). When both factors were considered together, there was no overall change in blood viscosity (from 3.97 to 4.03 cP at 300 s(-1)). The effects of exercise-induced haemoconcentration, increased plasma viscosity and increased red blood cell aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell deformability (e.g. red blood cell membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. PMID- 26682657 TI - Implementing the Mother-Baby Model of Nursing Care Using Models and Quality Improvement Tools. AB - As family-centered care has become the expected standard, many facilities follow the mother-baby model, in which care is provided to both a woman and her newborn in the same room by the same nurse. My facility employed a traditional model of nursing care, which was not evidence-based or financially sustainable. After implementing the mother-baby model, we experienced an increase in exclusive breastfeeding rates at hospital discharge, increased patient satisfaction, improved staff productivity and decreased salary costs, all while the number of births increased. Our change was successful because it was guided by the use of quality improvement tools, change theory and evidence-based practice models. PMID- 26682658 TI - An Evidence Review and Model for Prevention and Treatment of Postpartum Posttraumatic Stress Disorder. AB - Postpartum posttraumatic stress disorder (P-PTSD) is a variant of posttraumatic stress disorder (PTSD) that, although relatively prevalent, is under-researched. Up to one-third of women in the United States describe childbirth as traumatic, with 9 percent of women meeting the criteria for PTSD outlined by the American Psychiatric Association. These statistics are sobering in light of common use of analgesia during birth as well as hospital birth environments promoting family centered maternity care. How can a seemingly natural event, such as childbirth, be associated with PTSD? This review includes a description of key variables associated with P-PTSD. Socioeconomic, environmental and genetic determinants are discussed, as are evidence-based prevention and treatment approaches. PMID- 26682659 TI - Strategies for Providing Low-Cost Water Immersion Therapy With Limited Resources. AB - At our university-affiliated medical center, a major renovation of the women's health and birthing unit resulted in the temporary loss of the permanent tub used for water immersion therapy during labor. Because 40 percent of the women in the nurse-midwifery practice utilize hydrotherapy, we undertook a rigorous search for an interim solution. We developed a safe and cost-effective strategy that can be easily replicated and utilized by others to provide hydrotherapy for laboring women. PMID- 26682660 TI - Postresuscitation Care and Pretransport Stabilization of Newborns Using the Principles of STABLE Transport. AB - The practice of perinatal regionalization is designed to ensure that newborns are born in facilities with a care level designation that is consistent with expected pregnancy outcomes. Regionalization practices have resulted in lower neonatal mortality and morbidity rates. However, despite regionalization efforts, approximately 10 percent of newborns will require some level assistance with breathing, and a few (<1 percent) will require resuscitation in the birthing room. After resuscitation, many of these newborns require acute transport to a different facility. This column provides an overview of principles from the STABLE Program, which guides clinicians in providing postresuscitation care and pretransport stabilization for compromised newborns. PMID- 26682661 TI - Reducing the Risk of Alcohol Use Disorders in Women. AB - Nurses and other clinicians help women to examine their lifestyles and consider changes to promote optimum health. When the question is about drinking alcohol, what is appropriate to recommend? While moderate intake may be beneficial for cardiovascular and bone health, drinking more than the recommended amount increases the risk of harmful effects. This column examines guidelines for moderate alcohol consumption for women, reviews the assessment process and demonstrates an example of a brief intervention. A program of screening, brief intervention and referral to treatment (termed SBIRT by the Substance Abuse and Mental Health Services Administration) should be part of the standard assessment for every woman. Ongoing assessment of alcohol consumption can help to better target behaviors for early intervention. PMID- 26682662 TI - Salpingectomy and Ovarian Cancer Prevention. AB - Ovarian cancer is a major health concern for women. Women are often diagnosed late in the course of the disease, making the mortality rate high. Currently, screening methods for ovarian cancer are limited and, therefore, prevention methods remain an area of focus for researchers. Recent research has examined the salpingectomy and tubal ligation/sterilization as a prevention method for ovarian cancer. This column takes a second look at two recent research studies that examine salpingectomy and tubal ligation/sterilization as a method of ovarian cancer risk reduction. PMID- 26682663 TI - Preventing Fetal Alcohol Spectrum Disorders. PMID- 26682664 TI - Sharing Knowledge to Promote Evidence-Based Practice Around the World. PMID- 26682665 TI - Fetal Heart Monitoring. PMID- 26682666 TI - Mood and Anxiety Disorders in Pregnant and Postpartum Women. PMID- 26682667 TI - A Nurse's Heart. PMID- 26682668 TI - Multilevel Differences in Spontaneous Social Attention in Toddlers With Autism Spectrum Disorder. AB - This study examined the latent structure of spontaneous social attention in 11- to 26-month-olds with autism spectrum disorder (ASD, n = 90) and typically developing (n = 79) controls. Application of the joint and individual variance explained decomposition technique revealed that attention was driven by a condition-independent tuning into the dynamic social scenes construct and context specific constructs capturing selection of the most relevant social features for processing. Gaze behavior in ASD is characterized by a limited tuning into the social scenes and by a selection of atypical targets for processing. While the former may be due to early disruption of the reward circuitry leading to limited appreciation of the behavioral relevance of social information, the latter may represent secondary deficits reflecting limited knowledge about social partners. PMID- 26682669 TI - Interventional articular and para-articular knee procedures. AB - The knee is a common area of the body to undergo interventional procedures. This article discusses image-guided interventional issues specific to the knee area. The soft tissues in and around the knee are frequently affected by sport-related injuries and often need image-guided intervention. This article details the specific technical issues related to intervention in these soft tissues, including the iliotibial tract, fat pads, patellar tendon and other tendons, bursae and the meniscus. Most often, simple procedures such as injection and aspiration are performed without image guidance. Rarely image-guided diagnostic arthrography and therapeutic joint injections are necessary. The technique, indications and diagnostic considerations for arthrography are discussed in this article. Primary bone and soft-tissue tumours may involve the knee and adjacent soft tissues. Image-guided biopsies are frequently necessary for these lesions; this article details the technical issues related to image-guided biopsy around the knee. A number of newer ablation treatments are now available, including cryoablation, high-frequency ultrasound and microwave ablation. Radiofrequency ablation, however, still remains the most commonly employed ablation technique. The indications, technical and therapeutic considerations related to the application of this technique around the knee are discussed here. Finally, we briefly discuss some newer, but as of yet, unproven image-guided interventions for osteochondral lesions and Brodie's abscess. PMID- 26682670 TI - A proper adjustment for sicker patients with out-of-hospital cardiac arrest. PMID- 26682671 TI - Out-of-hospital cardiac arrest studies must adjust for sicker patients properly. PMID- 26682672 TI - The suprasternal notch as a landmark of chest compression depth in CPR. AB - OBJECTIVE: This study was performed to determine a landmark for chest compression depth for adult cardiopulmonary resuscitation (CPR) using chest computed tomography and to evaluate the validity of the landmark. METHODS: The external anteroposterior diameters (EAPDs) of each chest at the suprasternal notch (SN) and the lower half (LH) of the sternum were measured. We analyzed the differences in the EAPDs between the LH and the SN in each EAPD group in the LH of the sternum as follows: less than 20.00, 20.00 to 21.99, 22.00 to 23.99, greater than or equal to 24.00. We compared the differences in the EAPDs between the 2 points with 50 mm and the chest compression depth on simulated one-fourth external chest compressions for each EAPD group on the LH of the sternum. RESULTS: The mean difference in the EAPDs between the SN and the LH was 5.16 +/- 0.91 mm. The differences in the EAPDs between the SN and the LH of the sternum with 50 mm did not indicate a significant difference. The mean one-fourth EAPD at the LH of the sternum was 5.50 +/- 0.53 mm. There was not a significant difference in the residual chest depth on one-fourth simulated chest compression for each EAPD group on the LH of the sternum. CONCLUSIONS: The SN may have value as a functional landmark for chest compression depth in adult CPR. Our findings combined with the simulated one-fourth chest compressions were more consistent with the depth between 50 and 60 mm recommended by the 2015 CPR guidelines. PMID- 26682673 TI - Severe acidemia on arrival not predictive of neurologic outcomes in post-cardiac arrest patients. AB - PURPOSE: This study aimed to determine whether severe acidemia (pH <7.2) on arrival at the emergency department (ED) is a predictive factor for neurologic outcomes of post-cardiac arrest patients treated with targeted temperature management (TTM). MATERIALS AND METHODS: Data in the National Disaster Medical Center, a tertiary care hospital, were used to perform a case-control study on post-cardiac arrest patients treated with TTM from January 2013 to April 2015. The case group comprised patients with good neurologic outcomes (cerebral performance categories 1 and 2), whereas the control group comprised patients with poor neurologic outcomes (cerebral performance categories 3-5). Exposure was defined as arterial pH less than 7.2 on arrival at the ED. RESULTS: We identified 32 patients matching our criteria, of which 13 had good outcomes and 19 poor outcomes. Arterial pH on arrival was not significantly associated with neurologic outcomes (P = .47; odds ratio, 0.5; 95% confidence interval, 0.09-2.61). In 24 patients with cardiogenic causes of cardiac arrest, pH on arrival was not significantly associated with neurologic outcomes (P = .68; odds ratio, 0.5; 95% confidence interval, 0.09-2.73) after matched-pair analysis by age, sex, and presence of light reflex. CONCLUSION: Severe acidemia on arrival at the ED is not a significant predictive factor for neurologic outcomes in post-cardiac arrest patients treated with TTM, particularly in patients with cardiogenic causes of cardiac arrest. These results suggest that treatment should not be withheld in post-cardiac arrest patients with severe acidemia. PMID- 26682674 TI - Avascular necrosis of lunate bone: Kienbock disease. PMID- 26682675 TI - Seatbelt use during pregnancy. PMID- 26682676 TI - Direct cardiologist involvement in ED triage of cardiology patients. PMID- 26682677 TI - Impact of a clinical decision support tool on adherence to the Ottawa Ankle Rules. AB - OBJECTIVE: The objective of the study is to determine impact of a clinical decision support (CDS) tool on documented adherence to the Ottawa Ankle Rules (OAR) and utilization and yield of ankle/foot radiography, for emergency department patients with acute ankle injury. METHODS: This is a before-and-after intervention study conducted at a 793-bed, quaternary care, academic hospital from August 2012 to October 2013. Emergency department visits from adults with acute ankle injury 6 months before and 8 months after the intervention were included. The intervention embedded the OAR into a CDS tool integrated with a computerized physician order entry system, which had data capture capability and provided feedback at the time of ankle/foot radiography order. Primary outcome was rate of documented adherence to OAR. Secondary outcomes were utilization and yield (clinically significant fracture rates among patients with acute ankle injuries) of ankle/foot radiography. RESULTS: The study population included 460 visits; 205 (44.6%) occurred preintervention. After intervention, documented OAR adherence increased from 55.9% (229/410) to 95.7% (488/510; P < .001). Utilization remained stable for ankle (77.5%; P = .800) and foot (48.6%; P = .514) radiography. Yield remained stable for ankle (17.8%; P = .891) and foot (19.8%; P = .889) radiography. DISCUSSION: Lack of documentation of key clinical data may hamper provider communication, delay care coordination, and result in legal liability. By embedding the OAR into a CDS tool, we achieved the same rate of documented adherence as previous onerous educational implementations while automating data collection/retrieval. In summary, implementation of the OAR into a CDS tool was associated with an increase in documented adherence to the OAR. PMID- 26682678 TI - Vigilance for Salmonella in Feedstuffs Available in Costa Rica: Prevalence, Serotyping and Tetracycline Resistance of Isolates Obtained from 2009 to 2014. AB - Relevant epidemiological information is provided in this report for Salmonella based on data obtained from a Costa Rican surveillance program for animal feeds. In addition to prevalence, a description in terms of serotypes and tetracycline (TET) resistance of the isolates is included. A total of 1725 feed and feed ingredients samples were analyzed during 2009 and 2014, from which 110 Salmonella strains were recovered (76 from poultry, 23 from meat and bone meal [MBM], 3 from pet foods, and 8 from other feed). Retrieved isolates were serotyped and tested for minimum inhibitory concentration (MIC) against TET. Salmonella strains were found mainly from poultry feed (different growth stages, n = 76/110; 69.1%) and MBM (n = 23/109; 21.1%). The rest of the isolates were recovered from feather meal, pet food, fish meal (n = 3/110; 2.3% each) and swine feed (n = 1/110; 0.9%). From the different serotypes recovered (n = 21), the most common were Salmonella Give (n = 18; 13.8%) and Salmonella Rissen (n = 6; 4.6%) for MBM and Salmonella Havana (n = 14; 10.8%), Salmonella Rissen, Salmonella Soerenga, and Salmonella Schwarzengrund (n = 8; 6.2% each) in poultry feed. Recovered strains were regarded to be sensitive or have an intermediate resistance to TET as evidenced by their MIC50 and MIC90 concentrations of 4 and 8 MUg/mL for MBM and poultry feed, respectively. Compound feed and MBM samples exhibited strains characterized by 86.8 and 88.9% of the isolates classified (according to CLSI, 2015 ) as sensitive, 7.7 and 3.7% as intermediate, and 5.5% (with >256 MUg/mL as the highest concentration) and 7.4% (with 64 MUg/mL as the highest concentration) as resistant to TET, respectively. Salmonella serovars Anatum and Havana exhibited the highest resistance profile >256 and 128 MUg/mL, respectively. Hence, MBM and poultry feed seem to be a target of interest if Salmonella incidence is to be controlled. Serotypes recovered have in the past demonstrated pathogenic capability; therefore, hereafter a stricter surveillance program may be in order. PMID- 26682681 TI - Alterations in the Levels of Amyloid-beta, Phospholipid Hydroperoxide, and Plasmalogen in the Blood of Patients with Alzheimer's Disease: Possible Interactions between Amyloid-beta and These Lipids. AB - Aside from accumulation of amyloid-beta (Abeta) peptide in the brain, Alzheimer's disease (AD) has been reported as being associated with peroxidation of major phospholipids (e.g., phosphatidylcholine (PtdCho)) and degradation of antioxidative phospholipids (e.g., ethanolamine plasmalogen (PlsEtn)). In addition to its presence in the brain, Abeta is also found in blood; however, there is still little information about the levels of PtdCho hydroperoxide (PCOOH) and PlsEtn in the blood of patients with AD. In this study, by assuming a possible interaction among Abeta, PCOOH, and PlsEtn in blood circulation, we evaluated the levels of these molecules and correlations in blood samples that had been obtained from our former AD study for PCOOH measurement (Kiko et al., J Alzheimers Dis28, 593-600, 2012). We found that when compared to controls, plasma from patients with AD showed lower concentrations of PlsEtn species, especially PlsEtn bearing the docosahexaenoic acid (DHA) moiety. In addition, lower PlsEtn and higher PCOOH levels were observed in red blood cells (RBCs) of patients with AD. In both AD and control blood samples, RBC PCOOH levels tended to correlate with plasma levels of Abeta40, and each PlsEtn species showed different correlations with plasma Abeta. These results, together with in vitro data suggesting Abeta aggregation due to a decrease in levels of PlsEtn having DHA, led us to deduce that Abeta is involved in alterations in levels of PCOOH and PlsEtn species observed in the blood of patients with AD. PMID- 26682680 TI - Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer's Disease. AB - BACKGROUND: The neuropathological correlates of psychosis in Alzheimer's disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. OBJECTIVE: To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. METHOD: We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. RESULTS: 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. METHOD: Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD. PMID- 26682679 TI - Molecular Signaling Mechanisms of Natural and Synthetic Retinoids for Inhibition of Pathogenesis in Alzheimer's Disease. AB - Retinoids, which are vitamin A derivatives, interact through retinoic acid receptors (RARs) and retinoid X receptors (RXRs) and have profound effects on several physiological and pathological processes in the brain. The presence of retinoic acid signaling is extensively detected in the adult central nervous system, including the amygdala, cortex, hypothalamus, hippocampus, and other brain areas. Retinoids are primarily involved in neural patterning, differentiation, and axon outgrowth. Retinoids also play a key role in the preservation of the differentiated state of adult neurons. Impairment in retinoic acid signaling can result in neurodegeneration and progression of Alzheimer's disease (AD). Recent studies demonstrated severe deficiencies in spatial learning and memory in mice during retinoic acid (vitamin A) deprivation indicating its significance in preserving memory function. Defective cholinergic neurotransmission plays an important role in cognitive deficits in AD. All-trans retinoic acid is known to enhance the expression and activity of choline acetyltransferase in neuronal cell lines. Activation of RAR and RXR is also known to impede the pathogenesis of AD in mice by inhibiting accumulation of amyloids. In addition, retinoids have been shown to inhibit the expression of chemokines and pro-inflammatory cytokines in microglia and astrocytes, which are activated in AD. In this review article, we have described the chemistry and molecular signaling mechanisms of natural and synthetic retinoids and current understandings of their therapeutic potentials in prevention of AD pathology. PMID- 26682682 TI - Diminished CRE-Induced Plasticity is Linked to Memory Deficits in Familial Alzheimer's Disease Mice. AB - The mechanism underlying impaired learning and memory in Alzheimer's disease is not fully elucidated. The phosphorylation of cyclic-AMP response element binding protein (pCREB) in the hippocampus is thought to be a critical initiating step in the formation of long-term memories. Here, we tested CRE-driven gene expression following learning in mice harboring the familial Alzheimer's disease-linked APPswe/PS1DeltaE9 mutations using CRE-beta galactosidase reporter. We show that young adult APPswe/PS1DeltaE9 mice exhibit impaired recognition memory and reduced levels of pCREB, and its cofactors CREB binding protein (CBP) and p-300 following a learning task, compared to their wild type littermate counterparts. Impairments in learning-induced activation of CREB in these mice are manifested by reduced CRE-driven gene transcription. Importantly, expression of the CRE driven immediate early gene, Egr-1 (Zif268) is decreased in the CA1 region of the hippocampus. These studies implicate defective CREB-dependent plasticity in the mechanism underlying learning and memory deficits in Alzheimer's disease. PMID- 26682683 TI - Reduction of Amyloid-beta Plasma Levels by Hemodialysis: An Anti-Amyloid Treatment Strategy? AB - BACKGROUND: Cognitive impairment in hemodialysis patients is common, but the underlying pathogenesis remains unclear. Alzheimer's disease is the most common cause of dementia in the general elderly population. Histopathological hallmarks are, among others, senile plaques, which consist of amyloid-beta (Abeta). OBJECTIVE: To measure plasma levels of Abeta42 and Abeta40 during hemodialysis and to examine potential associations with cognitive performance in cognitively impaired hemodialysis patients. METHODS: Plasma samples of 26 hemodialysis patients were collected shortly before, after 50% of dialysis time, and at the end of a dialysis session. Abeta42 and Abeta40 levels were measured by a high sensitivity ELISA for human amyloid-beta. Cognition was tested under standardized conditions using the Montreal Cognitive Assessment (MoCA) as proposed previously. RESULTS: Clearance rates of both peptides during one dialysis session were 22% and 35% for Abeta42 and Abeta40, respectively. Abeta42 but not Abeta40 baseline levels were significantly associated with MoCA test results (r = 0.654, p = 0.001). CONCLUSION: In cognitively impaired hemodialysis patients plasma Abeta42 levels were associated with cognitive performance and both Abeta42 and Abeta40 plasma levels could be effectively reduced by dialysis. By inducing peripheral Abeta sink, hemodialysis may be considered as an anti-amyloid treatment strategy. PMID- 26682684 TI - Tobacco Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration. AB - BACKGROUND: Human studies suggest tobacco smoking is a risk factor for cognitive impairment and neurodegeneration, including Alzheimer's disease (AD). However, experimental data linking tobacco smoke exposures to underlying mediators of neurodegeneration, including impairments in brain insulin and insulin-like growth factor (IGF) signaling in AD are lacking. OBJECTIVE: This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of AD-associated proteins. METHODS: Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 or 8 weeks (CS4, CS8), or CS8 followed by 2 weeks recovery (CS8+R). Gene expression was measured by qRT-PCR analysis and proteins were measured by multiplex bead-based or direct binding duplex ELISAs. RESULTS: CS exposure effects on insulin/IGF and insulin receptor substrate (IRS) proteins and phosphorylated proteins were striking compared with the mRNA. The main consequences of CS4 or CS8 exposures were to significantly reduce insulin R, IGF-1R, IRS-1, and tyrosine phosphorylated insulin R and IGF-1R proteins. Paradoxically, these effects were even greater in the CS8+R group. In addition, relative levels of S312-IRS-1, which inhibits downstream signaling, were increased in the CS4, CS8, and CS8+R groups. Correspondingly, CS and CS8+R exposures inhibited expression of proteins and phosphoproteins required for signaling through Akt, PRAS40, and/or p70S6K, increased AbetaPP-Abeta, and reduced ASPH protein, which is a target of insulin/IGF-1 signaling. CONCLUSION: Secondhand CS exposures caused molecular and biochemical abnormalities in brain that overlap with the findings in AD, and many of these effects were sustained or worsened despite short-term CS withdrawal. PMID- 26682685 TI - Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings. AB - The Heidenhain variant defines a peculiar clinical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by isolated visual disturbances at disease onset and reflecting the early targeting of prions to the occipital cortex. Molecular and histopathological typing, thus far performed in 23 cases, has linked the Heidenhain variant to the MM1 sCJD type. To contribute a comprehensive characterization of cases with the Heidenhain variant, we reviewed a series of 370 definite sCJD cases. Eighteen patients (4.9%) fulfilled the selection criteria. Fourteen of them belonging to sCJD types MM1 or MM1+2C had a short duration of isolated visual symptoms and overall clinical disease, a high prevalence of periodic sharp-wave complexes in EEG, and a marked increase of cerebrospinal fluid proteins t-tau and 14-3-3 levels. In contrast, three cases of the MM 2C or MM 2+1C types showed a longer duration of isolated visual symptoms and overall clinical disease, non-specific EEG findings, and cerebrospinal fluid concentration below threshold for the diagnosis of "probable" CJD of both 14-3-3 and t-tau. However, a brain DWI-MRI disclosed an occipital cortical hyperintensity in the majority of examined cases of both groups. While confirming the strong linkage with the methionine genotype at the polymorphic codon 129 of the prion protein gene, our results definitely establish that the Heidenhain variant can also be associated with the MM 2C sCJD type in addition to the more common MM1 type. Likewise, our results highlight the significant differences in clinical evolution and laboratory findings between cases according to the dominant PrPSc type (type 1 versus type 2). PMID- 26682686 TI - Association between Coffee Consumption and Incident Risk of Disabling Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. AB - Epidemiological studies of the association between coffee consumption and dementia have yielded inconsistent results. Therefore, we investigated the association between coffee consumption and incident risk of dementia in an elderly Japanese population. 23,091 subjects aged >=65 y living in Ohsaki City, northeastern Japan, responded to the baseline survey in 2006. Of these, we analyzed 13,137 subjects who gave informed consent and were not disabled at baseline. The outcome was the incidence of disabling dementia defined by usage of the Long-term Care Insurance database. We used the Cox proportional hazards regression model for multivariate analysis. During 5.7 y of follow-up period, we identified 1,107 cases of incident dementia. Overall, coffee consumption was significantly associated with a lower risk of incident dementia. The multivariate adjusted HRs for the incidence of dementia according to coffee consumption categories (never, occasionally, 1-2 cups/d, and >=3 cups/d) were 1.00, 0.73 (95% CI, 0.62-0.86), 0.72 (95% CI, 0.61-0.84), and 0.82 (95% CI, 0.65-1.02; p for trend = 0.009), respectively. In addition, this significant inverse association was more remarkable among women, non-smokers, and non-drinkers. Coffee consumption is significantly associated with a lower risk of incident dementia. PMID- 26682687 TI - Multifunctional Effect of Human Serum Albumin Reduces Alzheimer's Disease Related Pathologies in the 3xTg Mouse Model. AB - Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifests simultaneously, eventually leading to cognitive impairment and death. No treatment is currently available; however, an agent addressing several key pathologies simultaneously has a better therapeutic potential. Human serum albumin (HSA) is a highly versatile protein, harboring multifunctional properties that are relevant to key pathologies underlying AD. This study provides insight into the mechanism for HSA's therapeutic effect. In vivo, a myriad of beneficial effects were observed by pumps infusing HSA intracerebroventricularly, for the first time in an AD 3xTg mice model. A significant effect on amyloid-beta (Abeta) pathology was observed. Abeta1-42, soluble oligomers, and total plaque area were reduced. Neuroblastoma SHSY5Y cell line confirmed that the reduction in Abeta1-42 toxicity was due to direct binding rather than other properties of HSA. Total and hyperphosphorylated tau were reduced along with an increase in tubulin, suggesting increased microtubule stability. HSA treatment also reduced brain inflammation, affecting both astrocytes and microglia markers. Finally, evidence for blood-brain barrier and myelin integrity repair was observed. These multidimensional beneficial effects of intracranial administrated HSA, together or individually, contributed to an improvement in cognitive tests, suggesting a non-immune or Abeta efflux dependent means for treating AD. PMID- 26682688 TI - The Anti-Amyloid-beta Monoclonal Antibody 4G8 Recognizes a Generic Sequence Independent Epitope Associated with alpha-Synuclein and Islet Amyloid Polypeptide Amyloid Fibrils. AB - Recently we reported that several monoclonal antibodies that recognize linear segments of amyloid-beta (Abeta) also recognize amyloid fibrils, but not monomers of unrelated sequences, indicating that recognition of a linear sequence segment is not a reliable indicator of sequence specificity. We asked whether any of the commonly used commercially available Abeta antibodies also recognize fibrils of unrelated sequence. Here we report that 4G8, which recognizes residues 18-23 of the Abeta sequence and is widely believed to be sequence-specific, also recognizes fibrils formed from alpha-synuclein and islet amyloid polypeptide (IAPP). The recognition of amyloid fibrils is aggregation-dependent because 4G8 does not recognize alpha-synuclein or IAPP monomer. 4G8 also stains fibrillar alpha-synuclein aggregates in human multiple system atrophy brain where it colocalizes with anti-alpha-synuclein monoclonal antibody LB509 immunoreactivity. We also found that LB509 recognizes Abeta fibrils, but not monomer, indicating that generic epitope-reactive antibodies are also produced in response to alpha synuclein immunization. Taken together, our results indicate that generic fibril conformational epitope specificity may be a pervasive property among monoclonal antibodies raised against amyloid-forming antigens and that the specificity of their immunoreactivity should be rigorously established and otherwise interpreted with caution. PMID- 26682689 TI - Progranulin Protein Levels in Cerebrospinal Fluid in Primary Neurodegenerative Dementias. AB - BACKGROUND: Progranulin is implicated in frontotemporal dementia (FTD), but its role in other neurodegenerative disorders is unknown. OBJECTIVE: To investigate the levels of progranulin (PGRN) in cerebrospinal fluid (CSF) in different neurodegenerative dementias and their correlation with levels in plasma in cognitively normal subjects. METHODS: We measured PGRN in CSF in 229 patients with amnestic mild cognitive impairment, Alzheimer's disease dementia, sporadic FTD, dementia with Lewy bodies, corticobasal syndrome, or progressive supranuclear palsy. We also measured PGRN in CSF and plasma in 74 cognitively normal individuals. We examined the correlation between PGRN levels in CSF and diagnosis, cortical thickness, genetic factors and other CSF biomarkers. We also investigated the correlation between plasma and CSF levels of PGRN in cognitively normal individuals. RESULTS: CSF levels did not differ across diagnoses or correlate with cortical thickness. Polymorphism rs5848 in GRN influenced CSF PGRN levels, but APOEE4 allele did not. Amyloid-beta42, t-tau, p-tau, and YKL-40 levels correlated weakly with PGRN in CSF. We found a weak correlation (r = 0.362) between plasma and CSF PGRN levels in cognitively normal individuals. CONCLUSIONS: Our findings do not support a diagnostic value of CSF PGRN in neurodegenerative diseases. Our data confirm that levels of PGRN in plasma do not reflect accurately levels in CSF in cognitively normal controls. These data should be considered in clinical trials aiming to increase PGRN. PMID- 26682690 TI - Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review. AB - Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity. PMID- 26682691 TI - Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People. AB - Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed. PMID- 26682692 TI - Safety and Tolerability of R(+) Pramipexole in Mild-to-Moderate Alzheimer's Disease. AB - Alzheimer's disease (AD) is an aging-related, degenerative brain disease of adults. Most (~95%) of AD occurs sporadically and is associated with early appearing deficits in brain regional glucose uptake, changes in cerebrospinal fluid (CSF) AD-related proteins, regional brain atrophy, and oxidative stress damage. We treated mild-moderate AD individuals with R(+)-pramipexole dihydrochloride (R(+)PPX), a neuroprotective, lipophilic-cation, free-radical scavenger that accumulates into brain and mitochondria. 19 subjects took R(+)PPX twice a day in increasing daily doses up to 300 mg/day under a physician-sponsor IND (60,948, JPB), IRB-approved protocol and quarterly external safety committee monitoring. 15 persons finished and contributed baseline and post-treatment serum, lumbar spinal fluid, brain 18F-2DG PET scans, and ADAS-Cog scores. ADAS Cog scores did not change (n = 1), improved (n = 2), declined 1-3 points (n = 5), or declined 4-13 points (n = 8) over 6 months of R(+)PPX treatment. Serum PPX levels were not related to changes in ADAS-Cog scores. Fasting AM serum PPX levels at 6 months varied considerably across subjects and correlated strongly with CSF [PPX] (r = 0.97, p < 0.0001). CSF [PPX] was not related to CSF [Abeta(42)], [Tau], or [P-Tau]. Regional 18F-2DG measures of brain glucose uptake demonstrated a 3-6% decline during R(+)PPX treatment. 56 mild-moderate adverse events occurred, 26 probably/definitely related to R(+)PPX use, with 4 withdrawals. R(+)PPX was generally well-tolerated and entered brain extracellular space linearly. Further studies of R(+)PPX in AD should include a detailed pharmacokinetic study of peak and trough serum [PPX] variations among subjects prior to planning any larger studies that would be needed to determine efficacy in altering disease progression. PMID- 26682693 TI - The Language Profile of Behavioral Variant Frontotemporal Dementia. AB - BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker. PMID- 26682694 TI - Impacts of High Serum Total Cholesterol Level on Brain Functional Connectivity in Non-Demented Elderly. AB - Epidemiological and clinical studies suggest that high serum cholesterol is a risk factor of dementia. However, the effects of cholesterol on cognition and brain remain largely unclear. This study aims to investigate the associations between serum total cholesterol (TC) and neuropsychological performance, and intrinsic functional networks in non-demented elderly. Among a cohort of 120 community-dwelling Beijing residents, 29 subjects in the high-TC group (1st quartile) and 31 in the low-TC group (4th quartile) were included in this study, and underwent a battery of neuropsychological tests and magnetic resonance imaging (MRI) scans, including T2- and T1-weighted imaging, and resting-state functional MRI. No significant group difference was found in any of the neuropsychological tests used. Stronger connectivity in the default mode network was observed in the high-TC group compared to that in the low-TC group (p < 0.001, uncorrected). While in the salience network (SN), the high-TC group showed lower connectivity in the anterior cingulate cortex and frontal regions, compared to the low-TC group (p < 0.05, FWE corrected). Our findings suggest that in non demented elderly persons, high serum cholesterol is associated with disruption of functional connectivity in the SN. The results not only deepen our understanding of how cholesterol affects the brain, but are also significant for selecting sensitive indicators for monitoring the impairments of cholesterol on the neural system. PMID- 26682695 TI - Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial. AB - BACKGROUND: Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. OBJECTIVE: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. METHODS: In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. RESULTS: The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. CONCLUSIONS: This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity. PMID- 26682696 TI - Detection of Alzheimer's Disease by Three-Dimensional Displacement Field Estimation in Structural Magnetic Resonance Imaging. AB - BACKGROUND: Within the past decade, computer scientists have developed many methods using computer vision and machine learning techniques to detect Alzheimer's disease (AD) in its early stages. OBJECTIVE: However, some of these methods are unable to achieve excellent detection accuracy, and several other methods are unable to locate AD-related regions. Hence, our goal was to develop a novel AD brain detection method. METHODS: In this study, our method was based on the three-dimensional (3D) displacement-field (DF) estimation between subjects in the healthy elder control group and AD group. The 3D-DF was treated with AD related features. The three feature selection measures were used in the Bhattacharyya distance, Student's t-test, and Welch's t-test (WTT). Two non parallel support vector machines, i.e., generalized eigenvalue proximal support vector machine and twin support vector machine (TSVM), were then used for classification. A 50 * 10-fold cross validation was implemented for statistical analysis. RESULTS: The results showed that "3D-DF+WTT+TSVM" achieved the best performance, with an accuracy of 93.05 +/- 2.18, a sensitivity of 92.57 +/- 3.80, a specificity of 93.18 +/- 3.35, and a precision of 79.51 +/- 2.86. This method also exceled in 13 state-of-the-art approaches. Additionally, we were able to detect 17 regions related to AD by using the pure computer-vision technique. These regions include sub-gyral, inferior parietal lobule, precuneus, angular gyrus, lingual gyrus, supramarginal gyrus, postcentral gyrus, third ventricle, superior parietal lobule, thalamus, middle temporal gyrus, precentral gyrus, superior temporal gyrus, superior occipital gyrus, cingulate gyrus, culmen, and insula. These regions were reported in recent publications. CONCLUSIONS: The 3D DF is effective in AD subject and related region detection. PMID- 26682697 TI - Prospective Memory Impairments in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia: Clinical and Neural Correlates. AB - BACKGROUND: Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. OBJECTIVE: To investigate the clinical and neural correlates of Time- and Event-based PM disruption in AD and the behavioral-variant FTD (bvFTD). METHODS: Twelve AD, 12 bvFTD, and 12 healthy older Control participants completed a modified version of the Cambridge Prospective Memory test, which examines Time- and Event-based aspects of PM. All participants completed a standard neuropsychological assessment and underwent whole-brain structural MRI. RESULTS: AD and bvFTD patients displayed striking impairments across Time- and Event-based PM relative to Controls, however, Time-based PM was disproportionately affected in the AD group. Episodic memory dysfunction and hippocampal atrophy were found to correlate strongly with PM integrity in both patient groups, however, dissociable neural substrates were also evident for PM performance across dementia syndromes. CONCLUSION: Our study reveals the multifaceted nature of PM dysfunction in neurodegenerative disorders, and suggests common and dissociable neurocognitive mechanisms, which subtend these deficits in each patient group. Future studies of PM disturbance in dementia syndromes will be crucial for the development of successful interventions to improve functional independence in the patient's daily life. PMID- 26682698 TI - Micrometer-Thick Graphene Oxide-Layered Double Hydroxide Nacre-Inspired Coatings and Their Properties. AB - Robust, functional, and flame retardant coatings are attractive in various fields such as building construction, food packaging, electronics encapsulation, and so on. Here, strong, colorful, and fire-retardant micrometer-thick hybrid coatings are reported, which can be constructed via an enhanced layer-by-layer assembly of graphene oxide (GO) nanosheets and layered double hydroxide (LDH) nanoplatelets. The fabricated GO-LDH hybrid coatings show uniform nacre-like layered structures that endow them good mechanic properties with Young's modulus of ~ 18 GPa and hardness of ~ 0.68 GPa. In addition, the GO-LDH hybrid coatings exhibit nacre like iridescence and attractive flame retardancy as well due to their well defined 2D microstructures. This kind of nacre-inspired GO-LDH hybrid thick coatings will be applied in various fields in future due to their high strength and multifunctionalities. PMID- 26682699 TI - MRI characteristics of carotid bulb atypical fibromuscular dysplasia in black stroke patients. AB - BACKGROUND AND PURPOSE: In black stroke patients, a particular form of fibromuscular dysplasia (FMD), called atypical FMD (aFMD), is involved in stroke mechanism. The high rate of stroke recurrence under medical treatment leads to propose surgery in such patients. Regarding its location level on the carotid bulb, aFMD is often confused with atherosclerosis or free-floating thrombus. Nowadays, only histology can confirm the diagnosis. MRI of aFMD has never been assessed. MATERIALS AND METHODS: The constitution of a black patient's cohort with aFMD-related ischemic stroke is currently in progress in the French West Indies, Martinique. In patients scheduled for surgery, MRI of the carotid bifurcation was analyzed preoperatively, with subsequent histological examination of the excised specimen. The first four black stroke patients with MRI and histological findings are described. RESULTS: On imaging, aFMD lesion was homogeneous with isosignal on T2-weighted sequences and slight hypersignal on T1 weighted sequences with mild gadolinium enhancement of the inner layer. Histological findings confirmed the aFMD mainly located in the intima. CONCLUSIONS: aFMD generates a particular MRI pattern in our four patients, which could increase the diagnosis accuracy. Carotid bulb lesion in black stroke patients should suggest aFMD and MRI analysis may contribute to rule out differential diagnoses. PMID- 26682700 TI - Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer. AB - BACKGROUND: Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products. HYPOTHESIS/OBJECTIVES: The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies. ANIMALS: Thirty-seven dogs treated with FDA approved or compounded lomustine. METHODS: Dogs that received compounded or FDA approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. RESULTS: Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within +/-10% of the labeled concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products. PMID- 26682701 TI - Pancreaticojejunostomy Versus Pancreaticogastrostomy After Pancreaticoduodenectomy: An Up-to-date Meta-Analysis. AB - BACKGROUND: The reconstruction of the pancreas after pancreaticoduodenectomy (PD) is a crucial factor in preventing postoperative complications as pancreatic anastomosis failure is associated with a high morbidity rate and contributes to prolonged hospitalization and mortality. Several techniques have been described for the reconstruction of pancreatic digestive continuity in the attempt to minimize the risk of a pancreatic fistula. The aim of this study was to compare the results of pancreaticogastrostomy and pancreaticojejunostomy after PD. METHODS: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) published up to January 2015 comparing patients with pancreaticogastrostomy (PG group) versus pancreaticojejunostomy (PJ group). Two reviewers independently assessed the eligibility and quality of the studies. The meta-analysis was conducted using either the fixed-effect or the random-effect model. RESULTS: Eight RCTs describing 1,211 patients were identified for inclusion in the study. The meta-analysis shows that the PG group had a significantly lower incidence rate of postoperative pancreatic fistulas [OR 0.64 (95% confidence interval 0.46-0.86), p = .003], intra-abdominal abscesses [OR 0.53 (95% CI, 0.33-0.85), p = .009] and length of hospital stay [MD -1.62; (95% CI 2.63-0.61), p = .002] than the PJ group, while biliary fistula, mortality, morbidity, rate of delayed gastric emptying, reoperation, and bleeding did not differ between the two groups. CONCLUSION: This meta-analysis suggests that the most effective treatment for reconstruction of pancreatic continuity after pancreatoduodenectomy is pancreaticogastrostomy. However, the advantage of the latter could potentially be demonstrated through further RCTs, including only patients at high risk of developing pancreatic fistulas. PMID- 26682702 TI - Discovery of (2-benzoylethen-1-ol)-containing 1,2-benzothiazine derivatives as novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting-based herbicide lead compounds. AB - A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine 1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha(-1). More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 MUM, which is better than the commercial herbicide sulctrione (IC50=0.53 MUM) and comparable with the commercial herbicide mesotrione (IC50=0.25 MUM). The structure-activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol) containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides. PMID- 26682703 TI - Fluorescent sulfonamide carbonic anhydrase inhibitors incorporating 1,2,3 triazole moieties: Kinetic and X-ray crystallographic studies. AB - Fluorescent sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) were essential for demonstrating the role played by the tumor-associated isoform CA IX in acidification of tumors, cancer progression towards metastasis and for the development of imaging and therapeutic strategies for the management of hypoxic tumors which overexpress CA IX. However, the presently available such compounds are poorly water soluble which limits their use. Here we report new fluorescent sulfonamides 7, 8 and 10 with increased water solubility. The new derivatives showed poor hCA I inhibitory properties, but were effective inhibitors against the hCA II (KIs of 366-127 nM), CA IX (KIs of 8.1-36.9 nM), CA XII (KIs of 4.1-20.5 nM) and CA XIV (KIs of 12.8-53.6 nM). A high resolution X ray crystal structure of one of these compounds bound to hCA II revealed the factors associated with the good inhibitory properties. Furthermore, this compound showed a three-fold increase of water solubility compared to a similar derivative devoid of the triazole moiety, making it an interesting candidate for ex vivo/in vivo studies. PMID- 26682705 TI - The impact of complications on quality of life following colorectal surgery: a prospective cohort study to evaluate the Clavien-Dindo classification system. AB - AIM: This prospective cohort study was performed to evaluate the impact of complications on quality of life (QOL) in colorectal surgery. The Clavien-Dindo complication classification (CDCC) is promising, but has not been evaluated by relating the classification to patient-reported outcome measures. METHOD: Patients undergoing colorectal surgery were evaluated prospectively 12 months postoperatively using the WHOQOL-BREF questionnaire. Patient data were prospectively recorded and complications were classified using the CDCC. Postoperative QOL in patients with minor and severe complications and patients without complications was compared using a general linear model. Relationships between CDCC and QOL were examined using correlations and multivariate regression. RESULTS: Of 218 patients, 130 (59.6%) had complications. In patients with severe complications there was a greater decrease in overall QOL (P = 0.043), QOL-physical (P < 0.001) and QOL-psychological (P = 0.013) domains in the first six postoperative weeks, whereas patients with minor complications had QOL scores comparable to those of patients without complications. QOL recovered to preoperative levels in all groups at 12 months. Change in QOL at 6 weeks was significantly correlated with CDCC grade, especially in the physical domain (Spearman's rho -0.287, P < 0.001). The presence of severe complications was an independent predictor of overall QOL, QOL-physical and QOL-psychological at 6 weeks. CONCLUSION: Severe complications are associated with reduced postoperative QOL at 6 weeks, but QOL recovers after 12 months. CDCC grade negatively correlates with change in QOL in the early postoperative period. These findings support the theoretical framework of the CDCC. PMID- 26682704 TI - Cytochrome P450 promiscuity leads to a bifurcating biosynthetic pathway for tanshinones. AB - Cytochromes P450 (CYPs) play a key role in generating the structural diversity of terpenoids, the largest group of plant natural products. However, functional characterization of CYPs has been challenging because of the expansive families found in plant genomes, diverse reactivity and inaccessibility of their substrates and products. Here we present the characterization of two CYPs, CYP76AH3 and CYP76AK1, which act sequentially to form a bifurcating pathway for the biosynthesis of tanshinones, the oxygenated diterpenoids from the Chinese medicinal plant Danshen (Salvia miltiorrhiza). These CYPs had similar transcription profiles to that of the known gene responsible for tanshinone production in elicited Danshen hairy roots. Biochemical and RNA interference studies demonstrated that both CYPs are promiscuous. CYP76AH3 oxidizes ferruginol at two different carbon centers, and CYP76AK1 hydroxylates C-20 of two of the resulting intermediates. Together, these convert ferruginol into 11,20-dihydroxy ferruginol and 11,20-dihydroxy sugiol en route to tanshinones. Moreover, we demonstrated the utility of these CYPs by engineering yeast for heterologous production of six oxygenated diterpenoids, which in turn enabled structural characterization of three novel compounds produced by CYP-mediated oxidation. Our results highlight the incorporation of multiple CYPs into diterpenoid metabolic engineering, and a continuing trend of CYP promiscuity generating complex networks in terpenoid biosynthesis. PMID- 26682706 TI - A Novel Top-k Strategy for Influence Maximization in Complex Networks with Community Structure. AB - In complex networks, it is of great theoretical and practical significance to identify a set of critical spreaders which help to control the spreading process. Some classic methods are proposed to identify multiple spreaders. However, they sometimes have limitations for the networks with community structure because many chosen spreaders may be clustered in a community. In this paper, we suggest a novel method to identify multiple spreaders from communities in a balanced way. The network is first divided into a great many super nodes and then k spreaders are selected from these super nodes. Experimental results on real and synthetic networks with community structure show that our method outperforms the classic methods for degree centrality, k-core and ClusterRank in most cases. PMID- 26682719 TI - Non-invasive exhaled volatile organic biomarker analysis to detect inflammatory bowel disease (IBD). AB - INTRODUCTION: Early inflammatory bowel disease (IBD) diagnosis remains a clinical challenge. Volatile organic compounds (VOCs) have shown distinct patterns in Crohn's disease (CD) and ulcerative colitis (UC). VOC production, reflecting gut fermentome metabolites, is perturbed in IBD. VOC sampling is non-invasive, with various compounds identified from faecal, breath and urine samples. This study aimed to determine if FAIMS (field asymmetric ion mobility spectroscopy) analysis of exhaled VOCs could distinguish IBD from controls. METHODS: Seventy-six subjects were recruited, 54 established IBD (25 CD, 29 UC) and 22 healthy controls. End expiratory breath was captured using a Warwick device and analysed by FAIMS. Data were pre-processed using wavelet transformation, and classification performed in a 10-fold cross-validation. Feature selection was performed using Wilcoxon rank sum test, and sparse logistic regression gave class predictions, to calculate sensitivity and specificity. RESULTS: FAIMS breath VOC analysis showed clear separation of IBD from controls, sensitivity: 0.74 (0.65 0.82), specificity: 0.75 (0.53-0.90), AUROC: 0.82 (0.74-0.89), p-value 6.2*10( 7). IBD subgroup analysis distinguished UC from CD: sensitivity of 0.67 (0.54 0.79), specificity: 0.67 (0.54-0.79), AUROC: 0.70 (0.60-0.80), p-value 9.23*10( 4). CONCLUSION: This confirms the utility of exhaled VOC analysis to distinguish IBD from healthy controls, and UC from CD. It conforms to other studies using different technology, whilst affirming exhaled VOCs as biomarkers for diagnosing IBD. PMID- 26682720 TI - The efficacy and safety of mammalian target of rapamycin inhibitors ab initio after liver transplantation without corticosteroids or induction therapy. AB - BACKGROUND: Mammalian target of rapamycin inhibitors have been used along with corticosteroids and/or induction therapy immediately after liver transplantation. Our aim was to assess the safety and tolerability of everolimus ab initio after liver transplantation without corticosteroids or induction, as well as efficacy in terms of liver function, rejection and graft loss. METHODS: A retrospective observational study of 50 adult patients (86% males, median age 54 years, range 25-68) who were liver transplanted between 2009 and 2013 and followed for 12 months. All recipients received everolimus plus low doses of calcineurin inhibitors (n=38) or mycophenolate (n=12) without corticosteroids and/or induction from the day of transplant. RESULTS: The overall patient and graft survival was 80%. Liver function was stable during one year follow-up. No rejections or graft loss were observed. Only five patients (10%) required therapy for onset dyslipidemia. CONCLUSION: Everolimus-based immunosuppression regimen without corticosteroids and/or induction immediately after liver transplantation seems to be safe and effective when administered with low doses of calcineurin inhibitor or mycophenolate; although these findings require further investigation, these regimens could avoid adverse effects of standard immunosuppression regimens with higher doses. PMID- 26682721 TI - A randomised controlled trial of perineural vs intravenous dexamethasone for foot surgery. AB - We used 20 ml ropivacaine 0.75% for ankle blocks before foot surgery in 90 participants who we allocated in equal numbers to: perineural dexamethasone 8 mg and intravenous saline 0.9%; perineural saline 0.9% and intravenous dexamethasone 8 mg; or perineural and intravenous saline 0.9%. Dexamethasone increased the median (IQR [range]) time for the return of some sensation or movement, from 14.6 (10.8-18.8 [5.5-38.0]) h with saline to 24.1 (19.3-29.3 [5.0-44.0]) h when given perineurally, p = 0.00098, and to 20.9 (18.3-27.8 [8.8-31.3]) h when given intravenously, p = 0.0067. Dexamethasone increased the median (IQR [range]) time for the return of normal neurology, from 17.6 (14.0-21.0 [9.5-40.5]) h with saline to 27.5 (22.0-36.3 [7.0-53.0]) h when given perineurally, p = 0.00016, and to 24.0 (20.5-32.3 [13.0-42.5]) h when given intravenously, p = 0.0022. Dexamethasone did not affect the rates of block success, postoperative pain scores, analgesic use, or nausea and vomiting. The route of dexamethasone administration did not alter its effects. PMID- 26682722 TI - Clinician recommendation of 12-step meeting attendance and discussion regarding disclosure of buprenorphine use among patients in office-based opioid treatment. AB - BACKGROUND: Clinicians are encouraged to include 12-step meetings, such as Alcoholics or Narcotics Anonymous (AA/NA), as ancillary services for the treatment for opioid use disorders (OUDs), even though some of these groups may not fully accept individuals receiving buprenorphine. Little is known about whether clinicians actually discuss with patients the issue of disclosure of buprenorphine use at 12-step meetings. METHODS: An anonymous survey was offered to patients enrolled in office-based opioid treatment with buprenorphine to assess whether their clinicians recommended attendance at 12-step meetings and discussed the issue of disclosing their use of buprenorphine to other members. The patients' attendance at 12-step meetings was also assessed, as well as beliefs and prior experiences related to disclosure of buprenorphine use at 12 step meetings. RESULTS: Thirty patients completed the survey. Twenty-one respondents (75.0%) indicated that they were encouraged to attend meetings, but only 9 (33.3%) reported having any discussion with their clinicians about the issue of disclosing their use of buprenorphine at meetings. The majority (76.7%) reported attending 12-step meetings at least occasionally, and 70% reported finding the meetings helpful. Nearly one third (30%) expressed concerns that other 12-step members would not accept them if their buprenorphine status were known, and a similar proportion (37%) frequently avoided disclosing their use of buprenorphine. CONCLUSIONS: Clinicians recommended 12-step meetings to most patients but did not routinely discuss issues of disclosure. Despite utilizing 12 step meetings and reporting them to be helpful, many avoided disclosing their use of buprenorphine to others. More research is needed to better understand how clinicians may assist patients to best utilize 12-step meetings. PMID- 26682723 TI - Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. AB - A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification. PMID- 26682724 TI - Metabolism profiles of nuciferine in rats using ultrafast liquid chromatography with tandem mass spectrometry. AB - Nuciferine (NF) is one of the main aporphine alkaloids existing in the traditional Chinese medicine Folium Nelumbinis (lotus leaves). Modern pharmacological studies have demonstrated that NF has a broad spectrum of bioactivities, such as anti-HIV and anti-hyperlipidemic effects, and has been recommended as a leading compound for new drug development. However, the metabolites and biotransformation pathway of NF in vivo have not yet been comprehensively investigated. The present study was performed to identify the metabolites of NF for exploring in vivo fates. Rat plasma and urine samples were collected after oral administration and prepared by liquid-liquid extraction with ethyl acetate. A method based on ultrafast liquid chromatography with tandem mass spectrometry was applied to identify the metabolites. Q1 (first quadrupole) full scan combined with a multiple reaction monitoring (MRM) survey scan were used for the detection of metabolites. MRM-information-dependent acquisition of enhanced product ions was used for the structural identification of detected metabolites. A total of 10 metabolites were identified, including phase I (demethylation, oxidation and dehydrogenation) and phase II (glucuronidation, sulfation and glutathione) biotransformation products. Demethylation is the main metabolic pathway of NF in the body. These results can help in improving understanding of the disposition and pharmacological mechanism of NF in the body. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26682725 TI - Reply to "Liver failure in human immunodeficiency virus - Hepatitis C virus coinfection treated with sofosbuvir, ledipasvir and antiretroviral therapy". PMID- 26682726 TI - Lipocalin 2 drives neutrophilic inflammation in alcoholic liver disease. AB - BACKGROUND & AIMS: Alcoholic steatohepatitis (ASH) is characterised by neutrophil infiltration that contributes to hepatic injury and disease. Lipocalin-2 (LCN2) was originally identified as siderophore binding peptide in neutrophils, which exerted tissue protective effects in several disease models. Here we investigate the role of LCN2 in the pathogenesis of alcohol-induced liver injury. METHODS: We compared hepatic LCN2 expression in ASH patients, alcoholic cirrhosis patients without evidence of ASH and patients with non-alcoholic fatty liver disease (NAFLD; i.e. simple steatosis). To mechanistically dissect LCN2 function in alcohol-induced liver injury, we subjected wild-type (WT) and Lcn2-deficient (Lcn2(-/-)) mice to the Lieber-DeCarli diet containing 5% ethanol (EtOH) or isocaloric maltose. Adoptive transfer experiments were performed to track neutrophil migration. Furthermore, we tested the effect of antibody-mediated LCN2 neutralisation in an acute model of ethanol-induced hepatic injury. RESULTS: Patients with ASH exhibited increased hepatic LCN2 immunoreactivity compared to patients with alcoholic cirrhosis or simple steatosis, which mainly localised to neutrophils. Similarly, ethanol-fed mice exhibited increased LCN2 expression that mainly localised to leukocytes and especially neutrophils. Lcn2(-/-) mice were protected from alcoholic liver disease (ALD) as demonstrated by reduced neutrophil infiltration, liver injury and hepatic steatosis compared to WT controls. Adoptive transfers revealed that neutrophil-derived LCN2 critically determines hepatic neutrophil immigration and persistence during chronic alcohol exposure. Antibody-mediated neutralisation of LCN2 protected from hepatic injury and neutrophilic infiltration after acute alcohol challenge. CONCLUSIONS: LCN2 drives ethanol-induced neutrophilic inflammation and propagates the development of ALD. Despite a critical role for LCN2 in immunity and infection, pharmacological neutralisation of LCN2 might be of promise in ALD. PMID- 26682727 TI - Liver failure in human immunodeficiency virus - Hepatitis C virus coinfection treated with sofosbuvir, ledipasvir and antiretroviral therapy. PMID- 26682728 TI - Staging for hepatocellular carcinoma: An embarrassment of riches. PMID- 26682729 TI - Regioselective Formation of Enol Esters from the Ruthenium-Catalyzed Markovnikov Addition of Carboxylic Acids to Alkynes. AB - The ruthenium complexes [Ru(CO)2(P(p-C6H4-X)3)2(O2CPh)2] (1a, X = CF3; 1b, X = Cl; 1c, X = H; 1d, X = Me; 1e, X = OMe) were successfully applied in the regioselective Markovnikov addition of carboxylic acids to terminal alkynes, yielding valuable enol esters. Catalyst screening revealed a significant influence of phosphine's electronic nature on activity and selectivity. The highest activity was achieved with catalyst 1a, featuring the most electron withdrawing phosphine ligand. Selectivity and activity could be further improved by the addition of catalytic amounts of AgOTf. Moreover, excellent selectivities with up to 99% of the Markovnikov product were achieved. The electronic influence of the substrates on the reaction rate was quantified by Hammett plots. By the use of electron-rich alkynes or highly acidic carboxylic acids, the reaction rate could be increased. Hence, the addition of highly acidic pentafluorobenzoic acid to electron-rich 4-methoxyphenylacetylene can even be carried out quantitatively at 25 degrees C within 4 h. Furthermore, a broad range of simple as well as electronically or sterically challenging substrates could be isolated in good to excellent yields with high regioselectivity and under mild reaction conditions (25-70 degrees C). The best reported activities and selectivities were obtained for the conversion of aromatic alkynes. PMID- 26682730 TI - Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1) in colorectal cancer (CRC) patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features. METHODS: Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS), disease-free survival (DFS) and clinicopathological features. RESULTS: 9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26-0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24-0.59, P < 0.0001, respectively). High ALDH1 expression was highly correlated with the tumor (T) stage (T3 + T4 vs. T1 + T2; OR = 2.16, 95%CI: 1.09-4.28, P = 0.03), lymph node (N) stage (N1 + N2 vs. N0; OR = 1.8; 95%CI: 1.17-2.79, P = 0.008), and tumor differentiation (G3 vs. G1 + G2; OR = 1.88; 95%CI: 1.07-3.30, P = 0.03). However, high ALDH1 expression was not significantly correlated with the patient age (>60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63-1.94, P = 0.72). CONCLUSIONS: High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age. PMID- 26682732 TI - Sound waves induce Volkov-like states, band structure and collimation effect in graphene. AB - We find exact states of graphene quasiparticles under a time-dependent deformation (sound wave), whose propagation velocity is smaller than the Fermi velocity. To solve the corresponding effective Dirac equation, we adapt the Volkov-like solutions for relativistic fermions in a medium under a plane electromagnetic wave. The corresponding electron-deformation quasiparticle spectrum is determined by the solutions of a Mathieu equation resulting in band tongues warped in the surface of the Dirac cones. This leads to a collimation effect of electron conduction due to strain waves. PMID- 26682734 TI - 2015 Lifetime Achievement Award of Tissue Engineering and Regenerative Medicine International Society-Americas: Antonios G. Mikos, PhD. PMID- 26682731 TI - Antitumor Effects and Mechanism of Novel Emodin Rhamnoside Derivatives against Human Cancer Cells In Vitro. AB - A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized and their anti-proliferative activities on cancer cell lines were investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited cell proliferation of a panel of different human cancer cell lines including A549, HepG2, OVCAR-3, HeLa and K562 and SGC-790 cell lines, and displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we found EM-d-Rha (3-(2",3"-Di-O-acetyl-alpha-L-rhamnopyranosyl-(1->4) 2',3'-di-O-acetyl-alpha-L-rhamnopyranosyl)-emodin) substantially induced cellular apoptosis of HepG2 and OVCAR-3 cells in the early growth stage. Furthermore, EM-d Rha led to the decrease of mitochondrial transmembrane potential, and up regulated the express of cells apoptosis factors in a concentration- and time dependent manner. The results indicated the EM-d-Rha may inhibit the growth and proliferation of HepG2 cells through the pathway of apoptosis induction, and the possible molecular mechanism may due to the activation of intrinsic apoptotic signal pathway. PMID- 26682735 TI - Discovery of Subtype Selective Janus Kinase (JAK) Inhibitors by Structure-Based Virtual Screening. AB - Janus kinase inhibitors represent a promising opportunity for the pharmaceutical intervention of various inflammatory and oncological indications. Subtype selective inhibition of these enzymes, however, is still a very challenging goal. In this study, a novel, customized virtual screening protocol was developed with the intention of providing an efficient tool for the discovery of subtype selective JAK2 inhibitors. The screening protocol involves protein ensemble-based docking calculations combined with an Interaction Fingerprint (IFP) based scoring scheme for estimating ligand affinities and selectivities, respectively. The methodology was validated in retrospective studies and was applied prospectively to screen a large database of commercially available compounds. Six compounds were identified and confirmed in vitro, with an indazole-based hit exhibiting promising selectivity for JAK2 vs JAK1. Having demonstrated that the described methodology is capable of identifying subtype selective chemical starting points with a favorable hit rate (11%), we believe that the presented screening concept can be useful for other kinase targets with challenging selectivity profiles. PMID- 26682736 TI - SAGA and GAIN for great apes. PMID- 26682737 TI - Subtraction CT angiography for the diagnosis of iliac arterial steno-occlusive disease. AB - PURPOSE: Accurate evaluation of stenosis in severely calcified arteries is a major challenge in conventional CT angiography (CTA) for peripheral arterial disease (PAD). The aim of this study was to evaluate the efficacy of subtraction CTA compared with conventional CTA and conventional angiography. MATERIALS AND METHODS: 175 arterial segments of 31 consecutive patients with PAD who underwent CTA and subsequent digital subtraction angiography (DSA) were evaluated. The percentage stenosis of diseased arteries was measured in iliac arteries with caliper methods on conventional CTA and subtraction CTA, and the concordance of each CTA method with DSA in the identification of >50 % stenosis was evaluated. Interpretation of CTA was always based only on maximum intensity projection (MIP). RESULTS: 174 (99 %) segments were interpretable on subtraction CTA and showed a good correlation with DSA (R (2) = 0.844), although 55 (31 %) segments were not evaluable on conventional CTA due to severe calcification. On subtraction CTA, the segmental accuracy, sensitivity, and specificity were 90.5, 78.9, and 80.0 %, respectively. CONCLUSION: Subtraction CTA is an accurate diagnostic tool for the evaluation of PAD. It may be easier to interpret stenosis in the presence of calcifications using subtraction CTA rather than with the conventional CTA approach. Also, subtraction CTA using only MIP presented a similar accuracy to DSA. PMID- 26682738 TI - Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy. AB - PURPOSE: Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed. METHODS: Eight patients with recurrent ependymomas fulfilling the criteria described below were evaluated. Inclusion criteria were: (1) the patient had previously undergone surgery and conventional radiotherapy as first-line treatment; (2) targets were located in or adjacent to the eloquent area or were deep-seated; and (3) the previously irradiated volume overlapped the target lesion. RESULTS: FSRT was delivered to 18 lesions, SRS to 20 lesions. A median follow-up period was 23 months. The local control rate was 76 % at 3 years. No significant differences in local control were observed due to tumor size or fractionation schedule. Lesions receiving >25 Gy/5 fr or 21 Gy/3 fr did not recur within 1 year, whereas no dose-response relationship was observed in those treated with SRS. No grade >=2 toxicity was observed. CONCLUSION: Our treatment protocol provided an acceptable LC rate and minimal toxicities. Because local recurrence of tumors may result in patient death, a minimum dose of 21 Gy/3 fr or 25 Gy/5 fr or higher may be most suitable for treatment of these cases. PMID- 26682739 TI - State of the art in rectal cancer surgery: Historical overview and new perspectives after the COLOR II trial. PMID- 26682741 TI - [Opening speech by the meeting president at the 99th German Society of Pathology annual meeting]. PMID- 26682740 TI - Hispanic-White Differences in Lifespan Variability in the United States. AB - This study is the first to investigate whether and, if so, why Hispanics and non Hispanic whites in the United States differ in the variability of their lifespans. Although Hispanics enjoy higher life expectancy than whites, very little is known about how lifespan variability-and thus uncertainty about length of life-differs by race/ethnicity. We use 2010 U.S. National Vital Statistics System data to calculate lifespan variance at ages 10+ for Hispanics and whites, and then decompose the Hispanic-white variance difference into cause-specific spread, allocation, and timing effects. In addition to their higher life expectancy relative to whites, Hispanics also exhibit 7 % lower lifespan variability, with a larger gap among women than men. Differences in cause specific incidence (allocation effects) explain nearly two-thirds of Hispanics' lower lifespan variability, mainly because of the higher mortality from suicide, accidental poisoning, and lung cancer among whites. Most of the remaining Hispanic-white variance difference is due to greater age dispersion (spread effects) in mortality from heart disease and residual causes among whites than Hispanics. Thus, the Hispanic paradox-that a socioeconomically disadvantaged population (Hispanics) enjoys a mortality advantage over a socioeconomically advantaged population (whites)-pertains to lifespan variability as well as to life expectancy. Efforts to reduce U.S. lifespan variability and simultaneously increase life expectancy, especially for whites, should target premature, young adult causes of death-in particular, suicide, accidental poisoning, and homicide. We conclude by discussing how the analysis of Hispanic-white differences in lifespan variability contributes to our understanding of the Hispanic paradox. PMID- 26682743 TI - Shift work and the risk of cardiovascular disease among workers in cocoa processing company, Tema. AB - OBJECTIVE: Shift work has been implicated in cardiovascular disease (CVD), a major cause of death globally. The aim of this study was to evaluate the risk of developing CVD in shift work. DESIGN: A cross-sectional study involving secondary analysis of shift and non-shift work from an industry in Ghana. PARTICIPANTS: Two hundred (113 shift and 87 non-shift) consecutive workers who consented were recruited into the study. A structured questionnaire was administered to deduce information on participant's age, alcohol consumption pattern, smoking habits, history of diabetes, stroke and hypertension. RESULTS: Shift workers were found to be associated with higher body mass index (26.9 +/- 4.6 vs 25.2 +/- 3.3, p = 0.013); fasting blood glucose (5.9 +/- 1.8 vs 5.3 +/- 0.8, p <= 0.0001); glycated haemoglobin (4.9 +/- 0.9 vs 4.2 +/- 0.8, p <= 0.0001); high sensitivity C reactive protein (2.5 +/- 1.1 vs 1.8 +/- 1.1, p < 0.0001); total cholesterol (5.9 +/- 1.3 vs 5.2 +/- 1.7, p = 0.002); triglycerides (1.3 +/- 0.8 vs 1.1 +/- 0.6, p = 0.015) and LDL cholesterol (3.6 +/- 0.9 vs 3.2 +/- 1.3, p = 0.04) than controls. Shift work however, had no associations with HDL-cholesterol. CONCLUSION: It can be concluded that shift work is associated with risk factors of CVD. PMID- 26682742 TI - Radiation treatment monitoring using multimodal functional imaging: PET/CT ((18)F Fluoromisonidazole & (18)F-Fluorocholine) and DCE-US. AB - BACKGROUND: This study aims to assess the effect of radiation treatment on the tumour vasculature and its downstream effects on hypoxia and choline metabolism using a multimodal approach in the murine prostate tumour model CWR22. Functional parameters derived from Positron Emission Tomography (PET)/Computer Tomography (CT) with (18)F-Fluoromisonidazole ((18)F-FMISO) and (18)F-Fluorocholine ((18)F FCH) as well as Dynamic Contrast-Enhanced Ultrasound (DCE-US) were employed to determine the relationship between metabolic parameters and microvascular parameters that reflect the tumour microenvironment. Immunohistochemical analysis was employed for validation. METHODS: PET/CT and DCE-US were acquired pre- and post-treatment, at day 0 and day 3, respectively. At day 1, radiation treatment was delivered as a single fraction of 10 Gy. Two experimental groups were tested for treatment response with (18)F-FMISO and (18)F-FCH. RESULTS: The maximum Standardized Uptake Values (SUVmax) and the mean SUV (SUVmean) for the (18)F FMISO group were decreased after treatment, and the SUVmean of the tumour-to muscle ratio was correlated to microvessel density (MVD) at day 3. The kurtosis of the amplitude of the contrast uptake A was significantly decreased for the control tumours in the (18)F-FCH group. Furthermore, the eliminating rate constant of the contrast agent from the plasma k el derived from DCE-US was negatively correlated to the SUVmean of tumour-to-muscle ratio, necrosis and MVD. CONCLUSIONS: The present study suggests that the multimodal approach using (18)F FMISO PET/CT and DCE-US seems reliable in the assessment of both microvasculature and necrosis as validated by histology. Thus, it has valuable diagnostic and prognostic potential for early non-invasive evaluation of radiotherapy. PMID- 26682744 TI - Naupliar and Metanaupliar Development of Thysanoessa raschii (Malacostraca, Euphausiacea) from Godthabsfjord, Greenland, with a Reinstatement of the Ancestral Status of the Free-Living Nauplius in Malacostracan Evolution. AB - The presence of a characteristic crustacean larval type, the nauplius, in many crustacean taxa has often been considered one of the few uniting characters of the Crustacea. Within Malacostraca, the largest crustacean group, nauplii are only present in two taxa, Euphauciacea (krill) and Decapoda Dendrobranchiata. The presence of nauplii in these two taxa has traditionally been considered a retained primitive characteristic, but free-living nauplii have also been suggested to have reappeared a couple of times from direct developing ancestors during malacostracan evolution. Based on a re-study of Thysanoessa raschii (Euphausiacea) using preserved material collected in Greenland, we readdress this important controversy in crustacean evolution, and, in the process, redescribe the naupliar and metanaupliar development of T. raschii. In contrast to most previous studies of euphausiid development, we recognize three (not two) naupliar (= ortho-naupliar) stages (N1-N3) followed by a metanauplius (MN). While there are many morphological changes between nauplius 1 and 2 (e.g., appearance of long caudal setae), the changes between nauplius 2 and 3 are few but distinct. They involve the size of some caudal spines (largest in N3) and the setation of the antennal endopod (an extra seta in N3). A wider comparison between free-living nauplii of both Malacostraca and non-Malacostraca revealed similarities between nauplii in many taxa both at the general level (e.g., the gradual development and number of appendages) and at the more detailed level (e.g., unclear segmentation of naupliar appendages, caudal setation, presence of frontal filaments). We recognize these similarities as homologies and therefore suggest that free-living nauplii were part of the ancestral malacostracan type of development. The derived morphology (e.g., lack of feeding structures, no fully formed gut, high content of yolk) of both euphausiid and dendrobranchiate nauplii is evidently related to their non-feeding (lecithotrophic) status. PMID- 26682745 TI - High Quantum Efficiency Nanopillar Photodiodes Overcoming the Diffraction Limit of Light. AB - InAs1-xSbx nanowires have recently attracted interest for infrared sensing applications due to the small bandgap and high thermal conductivity. However, previous reports on nanowire-based infrared sensors required low operating temperatures in order to mitigate the high dark current and have shown poor sensitivities resulting from reduced light coupling efficiency beyond the diffraction limit. Here, InAsSb nanopillar photodiodes with high quantum efficiency are achieved by partially coating the nanopillar with metal that excites localized surface plasmon resonances, leading to quantum efficiencies of ~29% at 2390 nm. These high quantum efficiency nanopillar photodiodes, with 180 nm diameters and 1000 nm heights, allow operation at temperatures as high as 220 K and exhibit a detection wavelength up to 3000 nm, well beyond the diffraction limit. The InAsSb nanopillars are grown on low cost GaAs (111)B substrates using an InAs buffer layer, making our device architecture a promising path toward low cost infrared focal plane arrays with high operating temperature. PMID- 26682746 TI - Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency. AB - Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies. PMID- 26682748 TI - Expression of cFLIPL Determines the Basal Interaction of Bcl-2 With Beclin-1 and Regulates p53 Dependent Ubiquitination of Beclin-1 During Autophagic Stress. AB - Autophagy and apoptosis are two different physiological processes, which is required for the maintenance of cellular homeostasis. The apoptosis associated proteins such as Bcl-2 and p53 have a close association with autophagic proteins HMGB1 and Beclin-1 to modulate autophagic signaling. We demonstrate here the involvement of anti-apoptotic protein cFLIPL in the regulation of autophagy during cellular stress. We found that ectopic expression of cFLIPL decreases the sensitivity of HEK 293T cells against rapamycin and H2 O2 induced autophagic stress. Notably, the selective knockdown of cFLIPL augments autophagic stress in the cells accompanied with JNK1 activation and p53 dependent ubiquitination of Beclin-1. However, re-expression of cFLIPL in cFLIP knockdown cells restores autophagic equilibrium collectively with reversible effects on JNK1 and Beclin-1 integrity. The co-immunoprecipitation analysis suggests that cFLIPL is essential to maintain the canonical interaction of Bcl-2 with Beclin-1 to regulate autophagic stress and cell death. Altogether, our findings suggest that expression of cFLIPL regulates the basal interaction of Bcl-2 with Beclin-1 and substantiates p53 dependent ubiquitination of Beclin-1 during autophagic stress to determine the fate of cell death or survival. J. Cell. Biochem. 117: 1757 1768, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26682747 TI - Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain. AB - BACKGROUND: Responsiveness to GH treatment can be estimated by both growth and ?IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF I/IGFBP-3 ratio and gain in height. METHODS: A multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 MUg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6-10.7). At onset of puberty, children were randomized into three groups, to receive 67 MUg/kg/day (GH(67)) given once (GH(67x1); n = 30) or divided into two daily injection (GH(33x2); n = 36), or to remain on a single 33 MUg/kg/day dose (GH(33x1); n = 38). The outcome measures were change and obtained mean on-treatment IGF-I(SDS), IGFBP3(SDS) and IGF I/IGFBP3 ratio(SDS) during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS. RESULTS: Mean prepubertal increases 1 year after GH start were: 2.1 IGF-I(SDS), 0.6 IGFBP3(SDS) and 1.5 IGF-I/IGFBP3ratio(SDS). A significant positive correlation was found between prepubertal ?IGFs and both prepubertal and total gain in height(SDS). During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF I(SDS) was higher in GH(67) vs GH(33) (p = 0.031). First year pubertal ?IGF I(SDS) was significantly higher in the GH(67)vs GH(33) group (0.5 vs -0.1, respectively, p = 0.007), as well as ?IGF-I(SDS) to the pubertal mean level (0.2 vs -0.2, p = 0.028). In multivariate analyses, the prepubertal increase in '?IGF I(SDS) from GH start' and the 'GH dose-dependent pubertal ?IGF-I(SDS)' were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in height(SDS). TRIAL REGISTRATION: TRN 88-177, not applicable 1988. CONCLUSION: The dose-dependent change in IGFs was related to a dose-dependent pubertal gain in height(SDS). The attempt to mimic normal physiology by giving a higher GH dose during puberty was associated with both an increase in IGF-I and a dose-dependent gain in height(SDS). PMID- 26682749 TI - Effects of Vitamin D and Exercise on the Wellbeing of Older Community-Dwelling Women: A Randomized Controlled Trial. AB - BACKGROUND: Evidence for the effects of exercise and vitamin D supplementation on quality of life (QoL), fear of falling (FoF) and mental wellbeing in older adults is conflicting. OBJECTIVE: To study the effects of vitamin D supplementation and multimodal group exercise on psychosocial functions of wellbeing, including QoL, mental wellbeing and FoF. METHOD: This is a 2-year, double-blind, placebo controlled vitamin D and open exercise intervention trial with 409 older Finnish women (70-80 years of age) randomized to 4 treatment arms: (1) placebo without exercise, (2) vitamin D (800 IU/day) without exercise, (3) placebo and exercise, and (4) vitamin D (800 IU/day) with exercise. Exercisers participated in group exercise twice per week for 12 months and once per week for the subsequent 12 months, plus home exercises. RESULTS: When comparing with the placebo without exercise group, there were no statistically significant differences between groups receiving either vitamin D, exercise or both treatments for changes in QoL or mental wellbeing (although a slight decline was seen in mental wellbeing in those receiving vitamin D only, p = 0.044). The initial slight reduction in FoF was significant in all intervention groups compared with controls (p < 0.05), but this was only temporary. CONCLUSION: Neither vitamin D nor exercise contributes to better QoL, FoF or mental wellbeing in community-dwelling healthy older women with sufficient vitamin D levels. PMID- 26682751 TI - Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression. AB - BACKGROUND/AIMS: Major depressive disorder is a common disease with serious morbidity, including increased risk of death from suicide. Major depressive disorder is treated with antidepressants. However, the molecular targets of antidepressants remained ill-defined and require further elucidation. METHODS: Mice were treated with corticosterone to induce stress, amitriptyline and the p38 kinase (p38K) inhibitor SB239063 or a combination of these drugs. Phosphorylation of p38K in hippocampal neurons was determined by immunostaining with a phospho specific antibody, neuronal proliferation using BrdU-labelling and behaviour employing a set of behavioural tests. RESULTS: Corticosterone induced phosphorylation/activation of p38K in the hippocampus in vivo. Antidepressants reversed the effect of corticosterone on p38K activation in wildtype mice, but had no effect in acid sphingomyelinase-deficient animals. Corticosterone also reduced neurogenesis and triggered depression-like behavioural changes, effects that were prevented by pharmacological inhibition of p38K. CONCLUSION: Stress induces p38K phosphorylation/activation in the hippocampus and thereby reduces neurogenesis and induces depression-like symptoms, events that are prevented by antidepressants via inhibition of the acid sphingomyelinase/ceramide system. PMID- 26682752 TI - Toward Automation of Insulin Delivery - Management Solutions for Type 1 Diabetes. AB - In the past decade, the field of type 1 diabetes was characterized by the efforts to integrate technology into the daily management of diabetes. Automated insulin delivery systems have emerged followed by the improvements in technology of pumps and sensors and automated close-loop systems that were developed around the world for overnight as well as for day and night use. Initially, these closed-loop systems were tested clinically in research centers, then at diabetes camps or hotels, and recently at patients' homes. The systems were tested in a wide range of populations of patients with type 1 diabetes: children, adolescents, adults, newly diagnosed, well and suboptimally controlled patients, the critically ill and pregnant women. The extensive clinical evaluation found these close-loop systems to be safe and efficient in controlling blood glucose levels. Now is the time to take these systems from research to industry and to get a regulatory approval of convenient devices for the use at home. Automated insulin delivery systems have the potential to change the way diabetes is treated and managed for the benefit of patients. This chapter summarizes the recent advances in this field. PMID- 26682750 TI - In vitro and in vivo anti-malarial activity of plants from the Brazilian Amazon. AB - BACKGROUND: The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. METHODS: Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei infected mice. RESULTS: High in vitro antiplasmodial activity (IC50 = 6.4-9.9 ug/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 ug/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls). CONCLUSIONS: Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present. PMID- 26682753 TI - Correction: CitSci.org: A New Model for Managing, Documenting, and Sharing Citizen Science Data. PMID- 26682754 TI - Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells. AB - PURPOSE: Cancer cells require massive amounts of amino acids for survival. LAT1 (L-type amino acid transporter 1) transports essential amino acids, including leucine, which trigger the downstream mTOR (mammalian target of rapamycin) pathway. We examined the association between androgen receptor and LAT1, and the association between LAT1 expression and the acquisition of castration resistance. MATERIALS AND METHODS: Western blot and real-time polymerase chain reaction were performed to study protein and mRNA expression. siRNA was used to knock down target genes. A total of 92 prostate biopsy specimens of patients who underwent androgen deprivation therapy were used for immunohistochemical analyses. Cox hazard proportional models and the Kaplan-Meier method were used for statistical analyses. RESULTS: LAT1 was highly expressed in hormone resistant prostate cancer cell lines. Knockdown of LAT1 in LNCaP and C4-2 cells significantly suppressed cell proliferation, migration and invasion. Androgen receptor siRNA or androgen receptor blocking through bicalutamide (10 MUM) or MDV3100 (10 MUM) significantly increased LAT1 expression (p <0.01). Treatment with dihydrotestosterone (0.1 to 10 nM) reduced LAT1 expression in a dose dependent manner (p <0.01). Bicalutamide/MDV3100 plus siLAT1 synergistically suppressed prostate cancer cell proliferation compared to single inhibition by androgen receptor or LAT1 (p <0.01). High LAT1 expression correlated with significantly shorter prostate specific antigen recurrence-free survival in patients receiving androgen deprivation therapy (p <0.0001). LAT1 expression was an independent predictor of castration resistance on multivariate analysis (HR 3.56, p = 0.0133). CONCLUSIONS: The current data may indicate a novel mechanism to acquire castration resistance through activation of the amino acid transporter LAT1. PMID- 26682755 TI - Percutaneous Nephrolithotomy in Children: 17 Years of Experience. AB - PURPOSE: We analyzed factors that might affect outcome in terms of success and incidence of complications in children up to 17 years after undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: The data of 346 renal units (294 patients) were analyzed in terms of postoperative outcome. Factors investigated that might affect outcome were patient gender, age, stone laterality, largest stone size, stone burden, number of stones, location of a single stone, previous intervention and instrument size. RESULTS: Mean +/- SD patient age was 8.51 +/- 4.91 years, and male-to-female ratio was 209:137. Mean +/- SD stone burden was 3.49 +/- 3.3 cm(2). Stone-free rates after a single procedure were 84.4% and 73.1% in patients with and without clinically insignificant residual stones, respectively. On univariate and multivariate analyses stone burden and number of stones affected the stone-free rate. Complications consisted of bleeding in 41 patients (11.8%), postoperative urinary tract infection in 21 (6%), urosepsis in 4 (0.1%) and hydrothorax in 4 (0.1%). One patient died of multiple organ failure. Through the years blood transfusion and complication rates decreased, and the use of smaller instruments increased significantly. Although bleeding occurred less often in cases where a 14Fr sheath was used rather than a larger sheath (5% vs 12%, p = 0.142), the difference was not significant. No significant factor affecting complication rates was detected. CONCLUSIONS: As in adults, percutaneous nephrolithotomy can be used in children with acceptable complication rates and good success rates for surgical treatment of complex renal stones. Number of stones and stone burden are predictive of postoperative stone-free rate. PMID- 26682756 TI - Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. AB - PURPOSE: Current standard imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Recently ligands of PSMA (prostate specific membrane antigen) were introduced in PET (positron emission tomography) of prostate cancer. Thus the aims of this retrospective analysis were to 1) investigate the diagnostic efficacy of (68)Ga-PSMA-PET imaging for lymph node staging in patients with prostate cancer scheduled for radical prostatectomy and 2) compare it to morphological imaging (computerized tomography and magnetic resonance tomography) with histopathological evaluation as the standard of reference. MATERIALS AND METHODS: A total of 130 patients with intermediate to high risk prostate cancer were staged with (68)Ga-PSMA-PET/magnetic resonance tomography or PET/computerized tomography from December 2012 to November 2014 before radical prostatectomy and template pelvic lymph node dissection. Histopathological findings of resected tissue were statistically correlated with the results of (68)Ga-PSMA-PET and morphological imaging in a patient and template based manner. RESULTS: Lymph node metastases were found in 41 of 130 patients (31.5%). On patient based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 65.9%, 98.9% and 88.5%, and those of morphological imaging were 43.9%, 85.4% and 72.3%, respectively. Of 734 dissected lymph node templates 117 (15.9%) showed metastases. On template based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 68.3%, 99.1% and 95.2%, and those of morphological imaging were 27.3%, 97.1% and 87.6%, respectively. On ROC analysis (68)Ga-PSMA-PET performed significantly better than morphological imaging alone on patient and template based analyses (p = 0.002 and <0.001, respectively). CONCLUSIONS: In patients with intermediate to high risk prostate cancer preoperative lymph node staging with (68)Ga-PSMA-PET proved to be superior to standard routine imaging. Thus it has the potential to replace current standard imaging for this indication if confirmed by prospective studies. PMID- 26682757 TI - Impact of Dry Mouth on Fluid Intake and Overactive Bladder Symptoms in Women taking Fesoterodine. AB - PURPOSE: We investigated the long-term relationships between dry mouth, fluid intake and overactive bladder symptoms in women undergoing treatment with fesoterodine. We hypothesized that women who experienced dry mouth would increase their fluid intake and worsen their urinary symptoms. MATERIALS AND METHODS: We conducted a prospective ancillary study to a 9-month open-label trial of fesoterodine for women with urgency urinary incontinence. Fluid intake was measured and compared according to reported dry mouth. Multivariable analysis was used to study the interaction between dry mouth, fluid intake and urinary symptoms. RESULTS: During the study 407 women without dry mouth significantly reduced their fluid intake (mean decrease 172.1 ml, median 118.3 ml, p = 0.02), while 91 women with dry mouth did not (mean decrease 95.8 ml, median 118.3 ml, p = 0.54). On univariable analysis a greater proportion of women who experienced dry mouth reported improvement in their urinary symptoms compared to women without dry mouth (60.5% vs 47.2%, p = 0.03). On multivariable analysis black women were less likely to report dry mouth (OR 0.4, 95% CI 0.2-0.9, p = 0.03) and older women were less likely to report improvement in urinary symptoms (OR 0.98, 95% CI 0.96-0.99, p = 0.003). Factors not associated with improvement in urinary symptoms on multiple regression were dry mouth, baseline fluid intake volume, change in fluid intake volume and caffeine intake volume. CONCLUSIONS: In women with overactive bladder receiving fesoterodine dry mouth may prevent restriction of fluid intake but does not diminish treatment efficacy. PMID- 26682758 TI - A Model to Optimize Followup Care and Reduce Hospital Readmissions after Radical Cystectomy. AB - PURPOSE: Radical cystectomy has one of the highest readmission rates across all surgical procedures at approximately 25%. We developed a mathematical model to optimize outpatient followup regimens for radical cystectomy. MATERIALS AND METHODS: We used delay-time analysis, a systems engineering approach, to maximize the probability of detecting patients susceptible to readmission through office visits and telephone calls. Our data source includes patients readmitted after radical cystectomy from the Healthcare Cost and Utilization Project State Inpatient Databases in 2009 and 2010 as well as from our institutional bladder cancer database from 2007 to 2011. We measured the interval from hospital discharge to the point when a patient first exhibits concerning symptoms. Our primary end point is 30-day hospital readmission. Our model optimized the timing and sequence of followup care after radical cystectomy. RESULTS: The timing of office visits and telephone calls is more important in detecting a patient at risk for readmission than the sequence of these encounters. Patients are most likely to exhibit concerning symptoms between 4 and 5 days after discharge home. An optimally scheduled office visit can detect up to 16% of potential readmissions, which can be increased to 36% with 1 office visit followed by 4 telephone calls. CONCLUSIONS: Our model improves the detection of concerning symptoms after radical cystectomy by optimizing the timing and number of outpatient encounters. By understanding how to design better outpatient followup care for patients treated with radical cystectomy we can help reduce the readmission burden for this population. PMID- 26682759 TI - The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment. AB - PURPOSE: Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. RESULTS: At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. CONCLUSIONS: Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. PMID- 26682760 TI - The stimulating role of subunit F in ATPase activity inside the A1-complex of the Methanosarcina mazei Go1 A1AO ATP synthase. AB - A1AO ATP synthases couple ion-transport of the AO sector and ATP synthesis/hydrolysis of the A3B3-headpiece via their stalk subunits D and F. Here, we produced and purified stable A3B3D- and A3B3DF-complexes of the Methanosarcina mazei Go1 A-ATP synthase as confirmed by electron microscopy. Enzymatic studies with these complexes showed that the M. mazei Go1 A-ATP synthase subunit F is an ATPase activating subunit. The maximum ATP hydrolysis rates (Vmax) of A3B3D and A3B3DF were determined by substrate-dependent ATP hydrolysis experiments resulting in a Vmax of 7.9 s(-1) and 30.4 s(-1), respectively, while the KM is the same for both. Deletions of the N- or C-termini of subunit F abolished the effect of ATP hydrolysis activation. We generated subunit F mutant proteins with single amino acid substitutions and demonstrated that the subunit F residues S84 and R88 are important in stimulating ATP hydrolysis. Hybrid formation of the A3B3D-complex with subunit F of the related eukaryotic V-ATPase of Saccharomyces cerevisiae or subunit epsilon of the F-ATP synthase from Mycobacterium tuberculosis showed that subunit F of the archaea and eukaryotic enzymes are important in ATP hydrolysis. PMID- 26682761 TI - Assembly of the Escherichia coli NADH:ubiquinone oxidoreductase (respiratory complex I). AB - Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, couples the electron transfer from NADH to ubiquinone with the translocation of four protons across the membrane. The Escherichia coli complex I is made up of 13 different subunits encoded by the so-called nuo-genes. The electron transfer is catalyzed by nine cofactors, a flavin mononucleotide and eight iron-sulfur (Fe/S) clusters. The individual subunits and the cofactors have to be assembled together in a coordinated way to guarantee the biogenesis of the active holoenzyme. Only little is known about the assembly of the bacterial complex compared to the mitochondrial one. Due to the presence of so many Fe/S-clusters the assembly of complex I is intimately connected with the systems responsible for the biogenesis of these clusters. In addition, a few other proteins have been reported to be required for an effective assembly of the complex in other bacteria. The proposed role of known bacterial assembly factors is discussed and the information from other bacterial species is used in this review to draw an as complete as possible model of bacterial complex I assembly. In addition, the supramolecular organization of the complex in E. coli is briefly described. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof. Conrad Mullineaux. PMID- 26682762 TI - SLAM family receptors in normal immunity and immune pathologies. AB - The signaling lymphocytic activation molecule (SLAM) family is a group of six receptors restricted to hematopoietic cells. Most of these receptors are self ligands, and thus are triggered in the context of interactions between hematopoietic cells. By way of their cytoplasmic domain, SLAM-related receptors associate with the SLAM-associated protein (SAP) family of adaptors, which control the signals and functions of SLAM family receptors. Recent findings have provided new insights into the key roles of SLAM family receptors in normal immunity, their involvement in human diseases and their usefulness as drug targets to treat human malignancies. These data are reviewed herein. PMID- 26682763 TI - Beyond the grave: When is cell death critical for immunity to infection? AB - Immune cell death is often observed in response to infection. There are three potential beneficial outcomes after host cell death: (1) the removal of an intracellular niche for microbes, (2) direct microbicidal activity of released components and (3) the propagation of an inflammatory response. Recent findings suggest that three forms of non-apoptotic regulated cell death, pyroptosis, necroptosis and NETosis, can impact on immunity to bacterial infection. However, it is challenging to design experiments that unequivocally prove the advantageous effects of regulated cell death on immunity. Recent advances in the genetic manipulation of regulated cell death and danger-associated molecular patterns and 'alarmins', such as HMGB1 and the IL-1 family, may hold the key to delineating the consequences of cell death in immunity to infection. PMID- 26682764 TI - Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person. AB - Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) kappa light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease. PMID- 26682767 TI - Molecular testing of cytology specimens: Are we ready for the new era? PMID- 26682766 TI - Spatiotemporal Variations in Chronic Obstructive Pulmonary Disease Mortality in China: Multilevel Evidence from 2006 to 2012. AB - Mortality of Chronic Obstructive Pulmonary Disease (COPD) is on the decline in China. It is not known if this trend occurs across all areas or whether spatiotemporal variations manifest. We used data from the nationally representative China Mortality Surveillance System to calculate annual COPD mortality counts (2006-2012) stratified by 5-year age groups (aged > 20), gender and time for 161 counties and districts (Disease Surveillance Points, or DSP). These counts were linked to annually adjusted denominator populations. Multilevel negative binomial regression with random intercepts and slopes were used to investigate spatiotemporal variation in COPD mortality adjusting for age, gender and area-level risk factors. COPD mortality rate decreased markedly from 105.1 to 73.7 per 100,000 during 2006 to 2012 and varied over two-fold between DSPs across China. Mortality rates were higher in the west compared with the east (Rate ratio (RR) 2.15, 95% confidence intervals (CI) 1.73, 2.68) and in rural compared with the urban (RR 1.87, 95% CI 1.55, 2.25). Adjustment for age, gender, urban/rural, region, smoking prevalence, indoor air pollution, mean body mass index and socioeconomic circumstances accounted for 67% of the geographical variation. Urban/rural differences in COPD mortality narrowed over time, but the magnitude of the east-west inequality persisted without change. Immediate action via large scale interventions to enhance the prevention and management of COPD are needed specifically within China's western region in order to tackle this crucial health inequality and leading preventable cause of death. PMID- 26682768 TI - Listeriosis Phytotherapy: A Review Study on the Effectiveness of Iranian Medicinal Plants in Treatment of Listeriosis. AB - Listeria monocytogenes can be found in many processed foods, raw milk, dairy products, meat and meat products such as sausages, beef and fish products, seafoods, eggs, fruits, and vegetables such as radish and cabbage. This article is a review study on the Iranian medicinal plants applied for treatment of listeriosis. Information of this review article was obtained by searching various key words such as Listeria monocytogenes, medicinal plants, plant extracts and essential oils among scientific articles published in databases of Google scholar, ISI Web of Knowledge, PubMed, Scopus, SID and Magiran. Thyme, German chamomile, great chamomile, yarrow, onion, oregano, nutmeg, sage, sagebrush, hyssop, rosemary, St John's wort, safflower, ajowan, cumin, peppermint, shallot, anise, and parsnip are known antilisteriosis medicinal plants. Bioactive phytochemicals, antioxidants and monoterpenes, sesquiterpene, coumarin, flavonoids, tannins, saponins, alkaloids, and terpenoids are the main ingredients of antilisteriosis medicinal plants. PMID- 26682769 TI - Dosimetric Performance of Newly Developed Farmer-Type Ionization Chamber in Radiotherapy Practice. AB - Dose measurement with ionization chamber is essential to deliver accurate dose to the tumor in radiotherapy. The cylindrical Farmer-type ionization chamber is recommended by various dosimetry protocols for dose measurement of radiotherapy beams. The air-equivalent graphite wall Farmer-type ionization chamber (FAR 65 GB) of active volume 0.65 cm3 with aluminum as the central electrode material was fabricated. Various dosimetric parameters were studied for the newly developed ionization chamber in cobalt-60, 6 and 18 MV photon beams. The preirradiation and postirradiation leakage of the chamber was within 0.08%. The long-term stability and the stem effect of the chamber were within 0.07% and 0.3%, respectively. The sensitivity of the ionization chamber was found to be 22.15 nC/Gy. The chamber shows linear response with dose for cobalt-60, 6 and 18 MV photon beams. The ion recombination correction factor increases with increase in bias voltage. For all energies and field sizes, the polarity correction factor is almost closer to unity. The ion recombination and polarity correction measurements show that the polarizing potential and polarity recommended during the calibration of ionization chamber should be used for routine measurement to avoid the uncertainty. The chamber response is independent of dose rate and energy. The chamber is cost-effective and shows precise and reproducible response. The study carried out confirms that the newly fabricated ion chamber can be used in the measurement of absolute dose for high-energy photon beams. PMID- 26682770 TI - Serum high-molecular-weight adiponectin level and incident dementia in patients with vascular risk factors. AB - BACKGROUND AND PURPOSE: The involvement of metabolic factors in the development of dementia has received much attention. However, previous studies have yielded conflicting results regarding how blood adipocytokine level impacts cognitive decline and dementia. This study aimed to clarify whether serum high-molecular weight (HMW) adiponectin level is related to incident dementia. METHODS: Data were from 466 patients (mean age 67.8 years, male 57%)--who had normal cognitive function and received brain magnetic resonance imaging--from amongst the 1106 patients in the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, a prospective cohort study of cardiovascular events and dementia amongst patients with vascular risk factors enrolled between 2001 and 2009. Baseline HMW adiponectin levels were measured using frozen serum. Dementia occurrence was examined in June 2013. RESULTS: Serum HMW adiponectin level was 4.33 +/- 2.95 MUg/ml; the levels were lower in men than in women and negatively correlated with body mass index. During the follow-up period (median 6.9 years), 47 patients had incident dementia including Alzheimer's disease dementia (27), vascular dementia (13), mixed dementia (four), other dementia (three). Risks of dementia in patients with high versus low HMW adiponectin levels were almost identical (P = 0.689). No association was found between adiponectin levels and Alzheimer's disease dementia or vascular dementia in the whole group or amongst men and women separately. CONCLUSIONS: This study demonstrated that serum HMW adiponectin level has little association with future dementia. Determination of metabolic factors involved in dementia requires evaluation of other biomarkers or parameters. PMID- 26682771 TI - Insights into Registered Nurses' professional values through the eyes of graduating students. AB - Professional values are integrated into undergraduate nursing curricula and taught in various ways. A significant influence on students' developing values and their definition of a 'good nurse' are the nurses they interact with in practice. The aim of this paper is to present the findings from a study that explored the professional values that graduating students viewed as important and how these values were illustrated in the behaviours of the nurses whose clinical practice they admired and wished to emulate. Fourteen students from one Australian university were interviewed on the last day of their final clinical placement. An interpretive qualitative design employing semi-structured interviews framed the study. Data were audio recorded, transcribed and thematically analysed. The participants' descriptions illustrated a range of professional values and behaviours. Four main professional values were identified, these included: being person-centred; kindness and caring; being in control; and commitment to learning. Findings demonstrated that the participants understood the meaning and relevance of professional nursing values, from a theoretical, moral and practical stance. Their responses also illustrated an appreciation of how these values influence patient care and the organisational culture as a whole. PMID- 26682772 TI - Differential Effects of Structural Modifications on the Competition of Chalcones for the PIB Amyloid Imaging Ligand-Binding Site in Alzheimer's Disease Brain and Synthetic Abeta Fibrils. AB - Alzheimer's disease (AD) is a complex brain disorder that still remains ill defined. In order to understand the significance of binding of different clinical in vivo imaging ligands to the polymorphic pathological features of AD brain, the molecular characteristics of the ligand interacting with its specific binding site need to be defined. Herein, we observed that tritiated Pittsburgh Compound B ((3)H-PIB) can be displaced from synthetic Abeta(1-40) and Abeta(1-42) fibrils and from the PIB binding complex purified from human AD brain (ADPBC) by molecules containing a chalcone structural scaffold. We evaluated how substitution on the chalcone scaffold alters its ability to displace (3)H-PIB from the synthetic fibrils and ADPBC. By comparing unsubstituted core chalcone scaffolds along with the effects of bromine and methyl substitution at various positions, we found that attaching a hydroxyl group on the ring adjacent to the carbonyl group (ring I) of the parent member of the chalcone family generally improved the binding affinity of chalcones toward ADPBC and synthetic fibrils F40 and F42. Furthermore, any substitution on ring I at the ortho-position of the carbonyl group greatly decreases the binding affinity of the chalcones, potentially as a result of steric hindrance. Together with the finding that neither our chalcones nor PIB interact with the Congo Red/X-34 binding site, these molecules provide new tools to selectively probe the PIB binding site that is found in human AD brain, but not in brains of AD pathology animal models. Our chalcone derivatives also provide important information on the effects of fibril polymorphism on ligand binding. PMID- 26682773 TI - Effect of Reinforcement on the Flexural Properties of Injection-Molded Thermoplastic Denture Base Resins. AB - PURPOSE: To evaluate the effect of reinforcement on the flexural properties of injection-molded thermoplastic denture base resins. MATERIALS AND METHODS: Three injection-molded thermoplastic denture base resins (polyamide, polyester, polycarbonate) were selected for this study, and a conventional heat-polymerized denture base resin (PMMA) was used as a control. Continuous unidirectional glass fiber-reinforced composite (FRC) and metal wire were used for reinforcement. Reinforced bar-shaped specimens (65 mm long, 10 mm wide, 3.3 mm high) were fabricated (n = 10). The flexural strength at the proportional limit (FS-PL) and the elastic modulus were measured using a three-point bending test. RESULTS: All the denture base material specimens reinforced with FRC possessed a significantly higher FS-PL compared to those without reinforcement. The FS-PL of the polycarbonate specimens reinforced with metal wire was significantly higher than that without reinforcement, and there was no significant difference in the FS-PL between the polycarbonate specimens reinforced with FRC and those with metal wire. The order of the elastic modulus according to the denture base material, arranged in terms of statistical significance, was as follows: PMMA (3.46 +/- 0.53 GPa) > polycarbonate (2.69 +/- 0.48 GPa) > polyester (2.00 +/- 0.39 GPa) > polyamide (1.14 +/- 0.35 GPa). The order of the elastic modulus according to the reinforcement, arranged in terms of statistical significance, was as follows: metal wire (2.74 +/- 0.96 GPa) > FRC (2.40 +/- 0.89 GPa) > no reinforcement (1.82 +/- 0.83 GPa). CONCLUSION: Continuous unidirectional glass fiber-reinforced composite (FRC) reinforcement had a satisfactory reinforcing effect for the injection-molded thermoplastic denture base resins. PMID- 26682774 TI - Porphyrin Metalation at MgO Surfaces: A Spectroscopic and Quantum Mechanical Study on Complementary Model Systems. AB - We show that both single-crystalline and nanostructured MgO surfaces convert free base tetraphenyl porphyrin (2HTPP) into magnesium tetraphenyl porphyrin (MgTPP) at room temperature. The reaction can be viewed as an ion exchange between the two aminic protons of the 2HTPP molecule with a Mg(2+) ion from the surface. The driving force for the reaction is the strong stability of the formed hydroxyl groups along the steps and at defects on the MgO surface. We have used an integrated characterization approach that includes UV/Vis diffuse reflectance measurements on nanostructured powders, X-ray photoelectron spectroscopic investigation of atomically clean MgO(100) single-crystalline thin films, and density functional theory (DFT) calculations on model systems. The DFT calculations demonstrate that MgTPP formation is strongly exothermic at the corners, edges and steps, but slightly endothermic on terrace sites. This agrees well with the UV/Vis diffuse reflectance, which upon adsorption of 2HTPP shows a decrease in the absorption band associated with corner and edge sites on MgO nanocube powders. PMID- 26682775 TI - Physical and Chemical Characterization of Real-World Particle Number and Mass Emissions from City Buses in Finland. AB - Exhaust emissions of 23 individual city buses at Euro III, Euro IV and EEV (Enhanced Environmentally Friendly Vehicle) emission levels were measured by the chasing method under real-world conditions at a depot area and on the normal route of bus line 24 in Helsinki. The buses represented different technologies from the viewpoint of engines, exhaust after-treatment systems (ATS) and fuels. Some of the EEV buses were fueled by diesel, diesel-electric, ethanol (RED95) and compressed natural gas (CNG). At the depot area the emission factors were in the range of 0.3-21 * 10(14) # (kg fuel)(-1), 6-40 g (kg fuel)(-1), 0.004-0.88 g (kg fuel)(-1), 0.004-0.56 g (kg fuel)(-1), 0.01-1.2 g (kg fuel)(-1), for particle number (EFN), nitrogen oxides (EFNOx), black carbon (EFBC), organics (EFOrg), and particle mass (EFPM1), respectively. The highest particulate emissions were observed from the Euro III and Euro IV buses and the lowest from the ethanol and CNG-fueled buses, which emitted BC only during acceleration. The organics emitted from the CNG-fueled buses were clearly less oxidized compared to the other bus types. The bus line experiments showed that lowest emissions were obtained from the ethanol-fueled buses whereas large variation existed between individual buses of the same type indicating that the operating conditions by drivers had large effect on the emissions. PMID- 26682776 TI - Computational modeling of oscillating fins that "catch and release" targeted nanoparticles in bilayer flows. AB - A number of physiological processes in living organisms involve the selective "catch and release" of biomolecules. Inspired by these biological processes, we use computational modeling to design synthetic systems that can controllably catch, transport, and release specific molecules within the surrounding solution, and, thus, could be harnessed for effective separation processes within microfluidic devices. Our system consists of an array of oscillating, microscopic fins that are anchored onto the floor of a microchannel and immersed in a flowing bilayer fluid. The oscillations drive the fins to repeatedly extend into the upper fluid and then tilt into the lower stream. The fins exhibit a specified wetting interaction with the fluids and specific adhesive interactions with nanoparticles in the solution. With this setup, we determine conditions where the oscillating fins can selectively bind, and thus, "catch" target nanoparticles within the upper fluid stream and then release these particles into the lower stream. We isolate the effects of varying the wetting interaction and the fins' oscillation modes on the effective extraction of target species from the upper stream. Our findings provide fundamental insights into the system's complex dynamics and yield guidelines for fabricating devices for the detection and separation of target molecules from complex fluids. PMID- 26682777 TI - Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF. AB - The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 degrees C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) = 0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a dosimetric measure in electromagnetic exposure risk assessments. PMID- 26682778 TI - Continued increases in hypertension over three decades in Fiji, and the influence of obesity. AB - OBJECTIVES: To analyse trends during 1980-2011 in hypertension prevalence and SBP/DBP by sex in Fiji Melanesian (i-Taukei) and Indian adults aged 25-64 years; and to assess effects of BMI. METHODS: Unit record data from five population based surveys were included (n = 14, 191). Surveys were adjusted to the nearest previous census to improve national representativeness. Hypertension was defined as SBP at least 140 mmHg and/or DBP at least 90 mmHg and/or on medication for hypertension. Regression (Poisson and linear) was used to assess period trends. RESULTS: Over 1980-2011 hypertension prevalence (%) and mean blood pressure (BP) (SBP/DBP mmHg) increased significantly (P < 0.001) in both sexes and ethnicities. Increases in hypertension were: from 16.2 to 41.3% in i-Taukei men (mean BP from 122/73 to 135/81); from 20.5 to 37.8% in Indian men (mean BP from 122/74 to 133/81); from 25.9 to 36.9% in i-Taukei women (mean BP from 126/76 to 132/81); and from 17.6 to 33.1% in Indian women (mean BP 117/71 to 130/81). The age adjusted trend in hypertension and mean BP (over 32 years) declined after adjusting for BMI, with effects of obesity greater in women than men, and in Indians than i-Taukei. BMI explained 45% of the age-adjusted increase in DBP over the period in Indians (both sexes), and 16% (men) and 38% (women) in i-Taukei. CONCLUSION: Significant increases have occurred in hypertension prevalence and SBP/DBP in both sexes and ethnicities of Fiji during 1980-2011 with no indication of decline, contributing to significant premature mortality from cardiovascular disease. PMID- 26682779 TI - Hypertension is associated with dysfunction of both peripheral and central auditory system. AB - OBJECTIVES: Arterial hypertension negatively influences the peripheral auditory system, causing sensorineural hearing loss. Much less is known about the detrimental effects of hypertension on the central auditory functions. METHODS: We tested 32 arterial hypertension patients and 32 age and sex-matched healthy volunteers with the expanded tonal audiometry (0.125-12.5 kHz), distortion product otoacoustic emissions (0.75-8 kHz), horizontal minimum audible angle test for eight azimuths with binaural stimulation and the random gap detection test. RESULTS: Peripheral hearing of the hypertensive patients was impaired in comparison with the controls within all audiometric frequencies (0.125-12.5 kHz) and within specific groups of frequencies. Distortion product otoacoustic emission results were significantly lower for frequencies 4 (P = 0.04) and 6 kHz (P < 0.001). The sound localization ability in the horizontal minimum audible angle test was significantly worse in the hypertensive patients in the 0 degrees , 45 degrees , 90 degrees , 135 degrees , and 270 degrees azimuth when the interaural pure tone average (0.5-1-2 kHz) was set less than 20 dB hearing level (P < 0.05), and in the 0 degrees , 90 degrees , 225 degrees , and 270 degrees azimuth when the binaural pure tone average (0.5-1-2 kHz) was set 20 dB or less hearing level (P < 0.05). Gap detection thresholds in the random gap detection test did not differ between the two groups. CONCLUSION: Arterial hypertension is independently related to the damage of the peripheral part of the auditory system resulting in high-frequency hearing loss. Hypertensive disturbances of central auditory processing are more discrete and concern the spatial hearing resolution. PMID- 26682780 TI - Soft drink consumption, mainly diet ones, is associated with increased blood pressure in adolescents. AB - OBJECTIVE: The aim of this cross-sectional study was to investigate the association between consumption of sugar-sweetened and diet soft drinks with blood pressure (BP) in adolescents. METHODS: Fifth graders of 20 public schools were invited to participate in an intervention aimed at behavioral dietary changes and had their BP, weight, and height measured at baseline. Type and frequency of soft drink consumption were assessed using a food and beverages frequency questionnaire, and students were classified as nonconsumers, sugar sweetened soft drink consumers, and diet soft drink consumers. RESULTS: Of the 574 students invited, 512 were examined and 488 had their BP measured. Of these, 25 (5.1%) reported to be nonconsumers, 419 (85.9%) were sugar-sweetened soft drink consumers, and 44 (9%) were diet soft drink consumers. Mean SBP and DBP were 101.3/57.8, 102.6/58.8, and 106.0/61.3 mmHg for these three groups of consumption, respectively. After adjustment for sex, age, BMI, physical activity, addition of salt to food, and education of the head of the family, SBP was 5.4 mmHg higher in the diet soft drink consumers group compared with the nonconsumers group and 3.3 mmHg higher compared with the sugar-sweetened consumers group (P value of trend = 0.01). Moreover, DBP was also higher among diet soft drink consumers compared with nonconsumers, with a difference of 3.3 mmHg, and compared with sugar-sweetened consumers, with a difference of 2.3 mmHg (P value of trend = 0.04). CONCLUSION: The results indicate that the consumption of soft drink is associated with increased BP, which is further increased by drinking diet type sodas. PMID- 26682781 TI - Mechanisms underlying elevated SBP differ with adiposity in young adults: the Enigma study. AB - OBJECTIVES: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals. The aim of the current study was to examine the influence of adiposity on the relationship between SBP and underlying haemodynamic mechanisms in young adults. METHOD: Data from 2502 patients were available from the Enigma study. Detailed demographic, biochemical, and haemodynamic data were obtained in all individuals. Data were analysed between lower and upper tertiles of BMI and SBP, separately for each sex. RESULTS: In normal-weight individuals, cardiac output (CO) was elevated in those with higher SBP, independently of body size. Moreover, higher CO was associated with an increased stroke volume in men (P < 0.001), but an increased heart rate in women (P = 0.002). In contrast, in overweight individuals, peripheral vascular resistance (PVR) was elevated in men with higher SBP (P = 0.02) and those with lower SBP had the lowest PVR of all groups. In linear regression analyses, there was a stronger association between SBP and CO in normal-weight individuals, but a stronger association between SBP and PVR in overweight individuals. CONCLUSION: Different haemodynamic mechanisms are associated with elevated SBP in young adults, depending on body size and sex. These data suggest the need for differential approaches to the identification and management of young adults with elevated BP. PMID- 26682782 TI - Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes: A systematic review and meta-analysis. AB - This review was undertaken to assess the effects of dipeptidyl peptidase-4 (DPP 4) inhibitors on blood pressure (BP) in patients with type 2 diabetes (T2DM). We searched three main databases (PubMed, Web of Science, and Scopus) for relevant articles. Randomized controlled trials which reported BP changes from baseline to study endpoint in patients with T2DM receiving treatment of DPP-4 inhibitors were included for analysis. Random effects models were used to measure the mean differences with 95% confidence intervals (CIs). Fifteen trials involving 5636 participants were identified. When compared with placebo or nontreatment, DPP-4 inhibitors achieved greater reductions for both SBP (mean difference, -3.04 mmHg; 95% CI, -4.37 to -1.72; P < 0.00001) and DBP (mean difference, -1.47 mmHg; 95% CI, -1.79 to -1.15; P < 0.00001). But the BP-lowering effects of sodium glucose cotransporter 2 inhibitors were more significant than those of DPP-4 inhibitors for both SBP (mean difference, 4.44 mmHg; 95% CI, 2.67-6.22; P < 0.00001) and DBP (mean difference, 2.15 mmHg; 95% CI, 1.08-3.21; P < 0.00001). No significant differences in BP changes were shown between DPP-4 inhibitors with other antidiabetic agents including glucagon-like peptide 1 receptor agonists, pioglitazone, sulphonylureas, metformin, and alpha-glucosidase inhibitors. DPP-4 inhibitors may exert modest BP-lowering effects compared with placebo or nontreatment for patients with T2DM, but no significant BP improvement was seen with this drug class when compared with other antidiabetic medications. PMID- 26682784 TI - DPP-4 inhibition and blood pressure lowering in perspective. PMID- 26682783 TI - Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation. AB - OBJECTIVES: The endothelium maintains vascular homeostasis through the release of endothelium-derived relaxing factors (EDRF) and endothelium-derived hyperpolarization (EDH). The balance in EDH : EDRF is disturbed in cardiovascular disease and may also be susceptible to developmental conditioning through exposure to an adverse uterine environment to predispose to later risk of hypertension and vascular disease. METHODS: Developmentally conditioned changes in EDH : EDRF signalling pathways were investigated in cremaster arterioles (18 32 MUm diameter) and third-order mesenteric arteries of adult male mice offspring of dams fed either a fat-rich (high fat, HF, 45% energy from fat) or control (C, 10% energy from fat) diet. After weaning, offspring either continued on high fat or were placed on control diets to give four dietary groups (C/C, HF/C, C/HF, and HF/HF) and studied at 15 weeks of age. RESULTS: EDH via intermediate (IKCa) and small (SKca) conductance calcium-activated potassium channels contributed less than 10% to arteriolar acetylcholine-induced relaxation in in-situ conditioned HF/C offspring compared with ~60% in C/C (P < 0.01). The conditioned reduction in EDH signalling in HF/C offspring was reversed in offspring exposed to a high-fat diet both before and after weaning (HF/HF, 55%, P < 0.01 vs. HF/C). EDH signalling was unaffected in arterioles from C/HF offspring. The changes in EDH : EDRF were associated with altered endothelial cell expression and localization of IKCa channels. CONCLUSION: This is the first evidence that EDH-mediated microvascular relaxation is susceptible to an adverse developmental environment through down-regulation of the IKCa signalling pathway. Conditioned offspring exposed to a 'second hit' (HF/HF) exhibit adaptive vascular mechanisms to preserve dilator function. PMID- 26682785 TI - The risk of visit-to-visit blood pressure variability in chronic kidney disease: cause or consequence. PMID- 26682786 TI - Prostasin, proteases, and preeclampsia. PMID- 26682788 TI - Obesity, diabetes, and antidiabetic treatment: blood pressure and vascular effects. PMID- 26682787 TI - The enigma of obesity-induced hypertension mechanisms in the youth. PMID- 26682789 TI - Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Systolic Heart Failure: The DEFEAT-HF Study. AB - OBJECTIVES: The primary objective of the study was a change in left ventricular end-systolic volume index (LVESVi) from baseline to 6 months of spinal cord stimulation (SCS) therapy in the treatment arm compared to the control arm as measured by echocardiography. Secondary objectives were changes in peak oxygen uptake and N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the treatment arm and control arm from baseline through 6 months. BACKGROUND: Abnormal neurohormonal activation is often responsible for progression of heart failure (HF). Treatment has often included drug therapy to modulate the neurohormonal axis. The purpose of the DEFEAT-HF (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure) clinical study was to evaluate whether direct modulation of the nervous system through SCS improved HF metrics, including heart size, biomarkers, functional capacity, and symptoms. METHODS: The DEFEAT-HF study was a prospective, multicenter randomized (3:2), parallel, single-blind, controlled study to investigate whether SCS was a feasible therapy for the treatment of systolic HF for patients with New York Heart Association functional class III HF, left ventricular ejection fraction (LVEF) <=35%, QRS duration <120 ms, and left ventricular end-diastolic dimension >=55 mm. The primary objective of the DEFEAT-HF study was to evaluate the reduction in LVESVi after 6 months of SCS therapy in the treatment arm compared to the control arm. RESULTS: In total, 81 patients were enrolled, with 66 successfully randomized and implanted with the SCS device system. Seventy-six percent (50 of 66) had an implantable cardioverter-defibrillator at the baseline visit. Among randomized patients, the mean age was 61 years, 79% were male, mean LVEF was 27%, and mean QRS duration was 105 ms. The change in LVESVi over 6 months was not significantly different between randomization arms (SCS OFF: -2.2 [95% confidence interval: -9.1 to 4.6] vs. SCS ON: 2.1 [95% confidence interval: 2.7 to 6.9]; p = 0.30). Analyses of secondary endpoints for the study were also not significantly different. CONCLUSIONS: The present study does not provide evidence to support a meaningful change in clinical outcomes for HF patients receiving SCS. (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure [DEFEAT-HF]; NCT01112579). PMID- 26682790 TI - Prevalence and Predictors of Sleep-Disordered Breathing in Patients With Stable Chronic Heart Failure: The SchlaHF Registry. AB - OBJECTIVES: This prospective study investigated the prevalence of sleep disordered breathing (SDB) and its predictors in patients with stable chronic heart failure (HF). BACKGROUND: SDB is increasingly recognized as being important in patients with HF. METHODS: The multicenter SchlaHF (Sleep-Disordered Breathing in Heart Failure) registry provides demographic and clinical data on chronic, stable, symptomatic patients with HF (New York Heart Association functional class >=II; left ventricular rejection fraction <=45%). Moderate-to-severe SDB (apnea hypopnea index >=15/h) was determined by a 2-channel screening device (ApneaLink, ResMed, Sydney, Australia). RESULTS: Data from 6,876 patients were analyzed. The prevalence of moderate-to-severe SDB was 46%, with a significant sex difference: 36% in women (n = 1,448) versus 49% in men (n = 5,428). Prevalence of SDB rose with increasing age (31%, 39%, 45%, 52%, and 59% in those age <=50, >50 to 60, >60 to 70, >70 to 80, and >80 years, respectively). Risk factors for SDB were body mass index (per 5 units; odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.22 to 1.36), left ventricular rejection fraction (per 5% decrement from 45%; OR: 1.10; 95% CI: 1.06 to 1.14), age (per 10-year difference to 60 years; OR: 1.41; 95% CI: 1.34 to 1.49), atrial fibrillation (OR: 1.19; 95% CI: 1.06 to 1.34), and male sex (OR: 1.90; 95% CI: 1.67 to 2.17). CONCLUSIONS: SchlaHF registry data demonstrate a high prevalence of SDB in a representative population of stable patients with chronic HF receiving contemporary medical management. Male sex, age, body mass index, and the severity of both symptoms and left ventricular dysfunction were clinical predictors for prevalent SDB. (Prevalence, Clinical Characteristics and Type of Sleep-disordered Breathing in Patients With Chronic, Symptomatic, Systolic Heart Failure; NCT01500759). PMID- 26682791 TI - Pathogenic Gut Flora in Patients With Chronic Heart Failure. AB - OBJECTIVES: The goal of this study was to measure the presence of pathogenic gut flora and intestinal permeability (IP) and their correlations with disease severity, venous blood congestion, and inflammation in patients with chronic heart failure (CHF). BACKGROUND: Evidence suggests that translocation of gut flora and/or their toxins from the intestine to the bloodstream is a possible trigger of systemic CHF inflammation. However, the relation between pathogenic gut flora and CHF severity, as well as IP, venous blood congestion as right atrial pressure (RAP), and/or systemic inflammation (C-reactive protein [CRP]), is still unknown. METHODS: This study analyzed 60 well-nourished patients in stable condition with mild CHF (New York Heart Association [NYHA] functional class I to II; n = 30) and moderate to severe CHF (NYHA functional class III to IV; n = 30) and matched healthy control subjects (n = 20). In all subjects, the presence and development in the feces of bacteria and fungi (Candida species) were measured; IP according to cellobiose sugar test results was documented. The study data were then correlated with RAP (echocardiography) and systemic inflammation. RESULTS: Compared with normal control subjects, the entire CHF population had massive quantities of pathogenic bacteria and Candida such as Campylobacter (85.3 +/- 3.7 CFU/ml vs. 1.0 +/- 0.3 CFU/ml; p < 0.001), Shigella (38.9 +/- 12.3 CFU/ml vs. 1.6 +/- 0.2 CFU/ml; p < 0.001), Salmonella (31.3 +/- 9.1 CFU/ml vs 0 CFU/ml; p < 0.001), Yersinia enterocolitica (22.9 +/- 6.3 CFU/ml vs. 0 CFU/ml; p < 0.0001), and Candida species (21.3 +/- 1.6 CFU/ml vs. 0.8 +/- 0.4 CFU/ml; p < 0.001); altered IP (10.2 +/- 1.2 mg vs. 1.5 +/- 0.8 mg; p < 0.001); and increased RAP (12.6 +/- 0.6 mm Hg) and inflammation (12.5 +/- 0.6 mg/dl). These variables were more pronounced in patients with moderate to severe NYHA functional classes than in patients with the mild NYHA functional class. Notably, IP, RAP, and CRP were mutually interrelated (IP vs. RAP, r = 0.55; p < 0.0001; IP vs. CRP, r = 0.78; p < 0.0001; and RAP vs. CRP, r = 0.78; p < 0.0001). CONCLUSIONS: This study showed that patients with CHF may have intestinal overgrowth of pathogenic bacteria and Candida species and increased IP associated with clinical disease severity, venous blood congestion, and inflammation. PMID- 26682792 TI - Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction. AB - OBJECTIVES: The present study investigated whether systemic, low-grade inflammation of metabolic risk contributed to diastolic left ventricular (LV) dysfunction and heart failure with preseved ejection fraction (HFpEF) through coronary microvascular endothelial activation, which alters paracrine signalling to cardiomyocytes and predisposes them to hypertrophy and high diastolic stiffness. BACKGROUND: Metabolic risk is associated with diastolic LV dysfunction and HFpEF. METHODS: We explored inflammatory endothelial activation and its effects on oxidative stress, nitric oxide (NO) bioavailability, and cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signalling in myocardial biopsies of HFpEF patients and validated our findings by comparing obese Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1)-HFpEF rats to ZSF1-Control (Ctrl) rats. RESULTS: In myocardium of HFpEF patients and ZSF1-HFpEF rats, we observed the following: 1) E-selectin and intercellular adhesion molecule-1 expression levels were upregulated; 2) NADPH oxidase 2 expression was raised in macrophages and endothelial cells but not in cardiomyocytes; and 3) uncoupling of endothelial nitric oxide synthase, which was associated with reduced myocardial nitrite/nitrate concentration, cGMP content, and PKG activity. CONCLUSIONS: HFpEF is associated with coronary microvascular endothelial activation and oxidative stress. These lead to a reduction of NO dependent signalling from endothelial cells to cardiomyocytes, which can contribute to the high cardiomyocyte stiffness and hypertrophy observed in HFpEF. PMID- 26682793 TI - Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial. AB - OBJECTIVES: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. BACKGROUND: Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. METHODS: In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide). RESULTS: For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF. CONCLUSIONS: BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure [HF] PATIENTS: A Randomised, Double-Blind Multicentre Study [CIBIS ELD]; ISRCTN34827306). PMID- 26682794 TI - Assessing the Risk of Progression From Asymptomatic Left Ventricular Dysfunction to Overt Heart Failure: A Systematic Overview and Meta-Analysis. AB - OBJECTIVES: This study sought to provide estimates of the risk of progression to overt heart failure (HF) from systolic or diastolic asymptomatic left ventricular dysfunction through a systematic review and meta-analysis. BACKGROUND: Precise population-based estimates on the progression from asymptomatic left ventricular dysfunction (or stage B HF) to clinical HF (stage C HF) remain limited, despite its prognostic and clinical implications. Pre-emptive intervention with neurohormonal modulation may attenuate disease progression. METHODS: MEDLINE and EMBASE were systematically searched (until March 2015). Cohort studies reporting on the progression from asymptomatic left ventricular systolic dysfunction (ALVSD) or asymptomatic left ventricular diastolic dysfunction (ALVDD) to overt HF were included. Effect estimates (prevalence, incidence, and relative risk) were pooled using a random-effects model meta-analysis, separately for systolic and diastolic dysfunction, with heterogeneity assessed with the I(2) statistic. RESULTS: Thirteen reports based on 11 distinct studies of progression of ALVSD were included in the meta-analysis assessing a total of 25,369 participants followed for 7.9 years on average. The absolute risks of progression to HF were 8.4 per 100 person-years (95% confidence interval [CI]: 4.0 to 12.8 per 100 person-years) for those with ALVSD, 2.8 per 100 person-years (95% CI: 1.9 to 3.7 per 100 person-years) for those with ALVDD, and 1.04 per 100 person-years (95% CI: 0.0 to 2.2 per 100 person-years) without any ventricular dysfunction evident. The combined maximally adjusted relative risk of HF for ALVSD was 4.6 (95% CI: 2.2 to 9.8), and that of ALVDD was 1.7 (95% CI: 1.3 to 2.2). CONCLUSIONS: ALVSD and ALVDD are each associated with a substantial risk for incident HF indicating an imperative to develop effective intervention at these stages. PMID- 26682795 TI - UVEAL MELANOMA EXTENSION TO THE OPTIC CHIASM. AB - PURPOSE: Case report describing a patient who developed intracranial extension of a uveal melanoma through the optic nerve. METHODS: We reviewed the patient's medical history and images. A 41-year-old woman who was blind in one eye had a uveal melanoma that extended through the optic nerve into the optic chiasm and involved the hypophysis. The patient then developed metastasis. RESULTS: The patient developed uveal melanoma extension into the optic chiasm through the optic nerve resulting in a visual field defect in the fellow eye. CONCLUSION: Uveal melanoma extension through the optic nerve is a devastating complication, which occurs anywhere from 0.6% to 3.7% in patients with uveal melanoma. If enucleation of the affected eye is performed, a representative portion of the optic nerve should be excised to decrease the risk of extension. Patients with phthisical eyes should undergo appropriate imaging techniques to prevent a missed diagnosis of optic nerve involvement. PMID- 26682796 TI - PERSISTENT RETINAL CHANGES AFTER INTRAVITREAL OCRIPLASMIN. AB - BACKGROUND/PURPOSE: Postmarket analysis helps identify potentially important side effects not discovered during clinical trials. Ocriplasmin is a recently approved medication administered by intravitreal injection for the treatment of symptomatic vitreomacular adhesion and macular hole. Overall, clinical trials of ocriplasmin have shown a relatively high safety profile. However, recently, a series of case reports have highlighted acute vision loss associated with abnormal findings on spectral domain optical coherence tomography and electroretinography. METHODS/RESULTS: A 70-year-old man developed multiple discrete pockets of macular subretinal fluid 10 weeks after intravitreal ocriplasmin injection, with minimal resolution of fluid over 11 months. Electroretinographic findings demonstrated persistent rod photoreceptor sensitivity loss at 14 months after injection. CONCLUSION: This is the first report of persistent electroretinographic and optical coherence tomographic abnormalities after ocriplasmin injection. Electroretinography abnormalities were noted in a small percentage of patients during ocriplasmin clinical trials and in a recent series of case reports and postmarket survey analysis. The authors propose that cleavage of fibronectin and laminin causes disruption of the interphotoreceptor matrix, leading to the ellipsoid layer attenuation and resultant electroretinographic sensitivity loss and subretinal fluid described on spectral domain optical coherence tomography. Persistent changes over 14 months in this patient indicate that ocriplasmin may have the potential to cause permanent retinal damage. PMID- 26682797 TI - piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts. AB - Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65+/-2% MD1 and 66+/-2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78+/-3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50+/-5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes. PMID- 26682799 TI - How likely is it that biological agents will be used deliberately to cause widespread harm? Policymakers and scientists need to take seriously the possibility that potential pandemic pathogens will be misused. PMID- 26682798 TI - The spliceosome-associated protein Nrl1 suppresses homologous recombination dependent R-loop formation in fission yeast. AB - The formation of RNA-DNA hybrids, referred to as R-loops, can promote genome instability and cancer development. Yet the mechanisms by which R-loops compromise genome instability are poorly understood. Here, we establish roles for the evolutionarily conserved Nrl1 protein in pre-mRNA splicing regulation, R-loop suppression and in maintaining genome stability. nrl1Delta mutants exhibit endogenous DNA damage, are sensitive to exogenous DNA damage, and have defects in homologous recombination (HR) repair. Concomitantly, nrl1Delta cells display significant changes in gene expression, similar to those induced by DNA damage in wild-type cells. Further, we find that nrl1Delta cells accumulate high levels of R-loops, which co-localize with HR repair factors and require Rad51 and Rad52 for their formation. Together, our findings support a model in which R-loop accumulation and subsequent DNA damage sequesters HR factors, thereby compromising HR repair at endogenously or exogenously induced DNA damage sites, leading to genome instability. PMID- 26682801 TI - Disordered Regions Flanking Ordered Domains Modulate Signaling Transduction. PMID- 26682800 TI - Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV. AB - Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood. Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explain impaired neuromuscular and secretory cells' functions that mediate regulated exocytosis. Here, we analyzed several forms of regulated exocytosis in a mouse model of MLIV and, opposite to expectations, we found enhanced exocytosis in secretory glands due to enlargement of secretory granules in part due to fusion with lysosomes. Preliminary exploration of synaptic vesicle size, spontaneous mEPSCs, and glutamate secretion in neurons provided further evidence for enhanced exocytosis that was rescued by re-expression of TRPML1 in neurons. These features were not observed in Niemann-Pick type C1. These findings suggest that TRPML1 may guard against pathological fusion of lysosomes with secretory organelles and suggest a new approach toward developing treatment for MLIV. PMID- 26682802 TI - Aging Gracefully: A New Model of Microtubule Growth and Catastrophe. PMID- 26682803 TI - The Nucleotide-Binding Sites of SUR1: A Mechanistic Model. AB - ATP-sensitive potassium (KATP) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. KATP channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the KATP channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the KATP channel's role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the KATP channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments. PMID- 26682805 TI - Reversible Effects of Peptide Concentration and Lipid Composition on H-Ras Lipid Anchor Clustering. AB - Dynamic clusters of lipid-anchored Ras proteins are important for high-fidelity signal transduction in cells. The average size of Ras nanoclusters was reported to be independent of protein expression levels, and cholesterol depletion is commonly used to test the raft-preference of nanoclusters. However, whether protein concentration and membrane domain stability affect Ras clustering in a reversible manner is not well understood. We used coarse-grained molecular dynamics simulations to examine the reversibility of the effects of peptide and cholesterol concentrations as well as a lipid domain-perturbing nanoparticle (C60) on the dynamics and stability of H-Ras lipid-anchor nanoclusters. By comparing results from these simulations with previous observations from the literature, we show that effects of peptide/cholesterol concentrations on the dynamics and stability of H-Ras peptide nanoclusters are reversible. Our results also suggest a correlation between the stabilities of lipid domains and Ras nanoclusters, which is supported by our finding that C60 penetrates into the liquid-disordered domain of the bilayer, destabilizing lipid domains and thereby the stability of the nanoclusters. PMID- 26682804 TI - In-Cell Solid-State NMR: An Emerging Technique for the Study of Biological Membranes. AB - Biological molecular processes are often studied in model systems, which simplifies their inherent complexity but may cause investigators to lose sight of the effects of the molecular environment. Information obtained in this way must therefore be validated by experiments in the cell. NMR has been used to study biological cells since the early days of its development. The first NMR structural studies of a protein inside a cell (by solution-state NMR) and of a membrane protein (by solid-state NMR) were published in 2001 and 2011, respectively. More recently, dynamic nuclear polarization, which has been used to enhance the signal in solid-state NMR, has also been applied to the study of frozen cells. Much progress has been made in the past 5 years, and in this review we take stock of this new technique, which is particularly appropriate for the study of biological membranes. PMID- 26682806 TI - Mechanics of Biomimetic Liposomes Encapsulating an Actin Shell. AB - Cell-shape changes are insured by a thin, dynamic, cortical layer of cytoskeleton underneath the plasma membrane. How this thin cortical structure impacts the mechanical properties of the whole cell is not fully understood. Here, we study the mechanics of liposomes or giant unilamellar vesicles, when a biomimetic actin cortex is grown at the inner layer of the lipid membrane via actin-nucleation promoting factors. Using a hydrodynamic tube-pulling technique, we show that tube dynamics is clearly affected by the presence of an actin shell anchored to the lipid bilayer. The same force pulls much shorter tubes in the presence of the actin shell compared to bare membranes. However, in both cases, we observe that the dynamics of tube extrusion has two distinct features characteristic of viscoelastic materials: rapid elastic elongation, followed by a slower elongation phase at a constant rate. We interpret the initial elastic regime by an increase of membrane tension due to the loss of lipids into the tube. Tube length is considerably shorter for cortex liposomes at comparable pulling forces, resulting in a higher spring constant. The presence of the actin shell seems to restrict lipid mobility, as is observed in the corral effect in cells. The viscous regime for bare liposomes corresponds to a leakout of the internal liquid at constant membrane tension. The presence of the actin shell leads to a larger friction coefficient. As the tube is pulled from a patchy surface, membrane tension increases locally, leading to a Marangoni flow of lipids. As a conclusion, the presence of an actin shell is revealed by its action that alters membrane mechanics. PMID- 26682807 TI - Characterization of the Functional Domains of a Mammalian Voltage-Sensitive Phosphatase. AB - Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to inositol lipid phosphatase activity. VSPs thus couple two signaling pathways that are critical for cellular functioning. Although a number of nonmammalian VSPs have been characterized biophysically, mammalian VSPs are less well understood at both the physiological and biophysical levels. In this study, we aimed to address this gap in knowledge by determining whether the VSP from mouse, Mm-VSP, is expressed in the brain and contains a functional voltage-sensing domain (VSD) and a phosphatase domain. We report that Mm-VSP is expressed in neurons and is developmentally regulated. To address whether the functions of the VSD and phosphatase domain are retained in Mm-VSP, we took advantage of the modular nature of these domains and expressed each independently as a chimeric protein in a heterologous expression system. We found that the Mm-VSP VSD, fused to a viral potassium channel, was able to drive voltage-dependent gating of the channel pore. The Mm-VSP phosphatase domain, fused to the VSD of a nonmammalian VSP, was also functional: activation resulted in PI(4,5)P2 depletion that was sufficient to inhibit the PI(4,5)P2-regulated KCNQ2/3 channels. While testing the functionality of the VSD and phosphatase domain, we observed slight differences between the activities of Mm-VSP-based chimeras and those of nonmammalian VSPs. Although the properties of VSP chimeras may not completely reflect the properties of native VSPs, the differences we observed in voltage-sensing and phosphatase activity provide a starting point for future experiments to investigate the function of Mm-VSP and other mammalian VSPs. In conclusion, our data reveal that both the VSD and the lipid phosphatase domain of Mm-VSP are functional, indicating that Mm-VSP likely plays an important role in mouse neurophysiology. PMID- 26682808 TI - Seeds of Locally Aligned Motion and Stress Coordinate a Collective Cell Migration. AB - We find how collective migration emerges from mechanical information transfer between cells. Local alignment of cell velocity and mechanical stress orientation a phenomenon dubbed "plithotaxis"-plays a crucial role in inducing coordinated migration. Leader cells at the monolayer edge better align velocity and stress to migrate faster toward the open space. Local seeds of enhanced motion then generate stress on neighboring cells to guide their migration. Stress-induced motion propagates into the monolayer as well as along the monolayer boundary to generate increasingly larger clusters of coordinately migrating cells that move faster with enhanced alignment of velocity and stress. Together, our analysis provides a model of long-range mechanical communication between cells, in which plithotaxis translates local mechanical fluctuations into globally collective migration of entire tissues. PMID- 26682809 TI - The Impact of Collagen Fibril Polarity on Second Harmonic Generation Microscopy. AB - In this work, we report the implementation of interferometric second harmonic generation (SHG) microscopy with femtosecond pulses. As a proof of concept, we imaged the phase distribution of SHG signal from the complex collagen architecture of juvenile equine growth cartilage. The results are analyzed in respect to numerical simulations to extract the relative orientation of collagen fibrils within the tissue. Our results reveal large domains of constant phase together with regions of quasi-random phase, which are correlated to respectively high- and low-intensity regions in the standard SHG images. A comparison with polarization-resolved SHG highlights the crucial role of relative fibril polarity in determining the SHG signal intensity. Indeed, it appears that even a well organized noncentrosymmetric structure emits low SHG signal intensity if it has no predominant local polarity. This work illustrates how the complex architecture of noncentrosymmetric scatterers at the nanoscale governs the coherent building of SHG signal within the focal volume and is a key advance toward a complete understanding of the structural origin of SHG signals from tissues. PMID- 26682810 TI - Superresolution Imaging of Aquaporin-4 Cluster Size in Antibody-Stained Paraffin Brain Sections. AB - The water channel aquaporin-4 (AQP4) forms supramolecular clusters whose size is determined by the ratio of M1- and M23-AQP4 isoforms. In cultured astrocytes, differences in the subcellular localization and macromolecular interactions of small and large AQP4 clusters results in distinct physiological roles for M1- and M23-AQP4. Here, we developed quantitative superresolution optical imaging methodology to measure AQP4 cluster size in antibody-stained paraffin sections of mouse cerebral cortex and spinal cord, human postmortem brain, and glioma biopsy specimens. This methodology was used to demonstrate that large AQP4 clusters are formed in AQP4(-/-) astrocytes transfected with only M23-AQP4, but not in those expressing only M1-AQP4, both in vitro and in vivo. Native AQP4 in mouse cortex, where both isoforms are expressed, was enriched in astrocyte foot-processes adjacent to microcapillaries; clusters in perivascular regions of the cortex were larger than in parenchymal regions, demonstrating size-dependent subcellular segregation of AQP4 clusters. Two-color superresolution imaging demonstrated colocalization of Kir4.1 with AQP4 clusters in perivascular areas but not in parenchyma. Surprisingly, the subcellular distribution of AQP4 clusters was different between gray and white matter astrocytes in spinal cord, demonstrating regional specificity in cluster polarization. Changes in AQP4 subcellular distribution are associated with several neurological diseases and we demonstrate that AQP4 clustering was preserved in a postmortem human cortical brain tissue specimen, but that AQP4 was not substantially clustered in a human glioblastoma specimen despite high-level expression. Our results demonstrate the utility of superresolution optical imaging for measuring the size of AQP4 supramolecular clusters in paraffin sections of brain tissue and support AQP4 cluster size as a primary determinant of its subcellular distribution. PMID- 26682811 TI - The Interaction between Influenza HA Fusion Peptide and Transmembrane Domain Affects Membrane Structure. AB - Viral glycoproteins, such as influenza hemagglutinin (HA) and human immunodeficiency virus gp41, are anchored by a single helical segment transmembrane domain (TMD) on the viral envelope membrane. The fusion peptides (FP) of the glycoproteins insert into the host membrane and initiate membrane fusion. Our previous study showed that the FP or TMD alone perturbs membrane structure. Interaction between the influenza HA FP and TMD has previously been shown, but its role is unclear. We used PC spin labels dipalmitoylphospatidyl tempo-choline (on the headgroup), 5PC and 14PC (5-C and 14-C positions on the acyl chain) to detect the combined effect of FP-TMD interaction by titrating HA FP to TMD-reconstituted 1,2-dimyristoyl-sn-glycero-3-phosphocholine/1,2 dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol)/cholesterol lipid bilayers using electron spin resonance. We found that the FP-TMD increases the lipid order at all positions, which has a greater lipid ordering effect than the sum of the FP or TMD alone, and this effect reaches deeper into the membranes. Although HA mediated membrane fusion is pH dependent, this combined effect is observed at both pH 5 and pH 7. In addition to increasing lipid order, multiple components are found for 5PC at increased concentration of FP-TMD, indicating that distinct domains are induced. However, the mutation of Gly1 in the FP and L187 in the TMD eliminates the perturbations, consistent with their fusogenic phenotypes. Electron spin resonance on spin-labeled peptides confirms these observations. We suggest that this interaction may provide a driving force in different stages of membrane fusion: initialization, transition from hemifusion stalk to transmembrane contact, and fusion pore formation. PMID- 26682812 TI - Modification of Salmonella Lipopolysaccharides Prevents the Outer Membrane Penetration of Novobiocin. AB - Small hydrophilic antibiotics traverse the outer membrane of Gram-negative bacteria through porin channels. Large lipophilic agents traverse the outer membrane through its bilayer, containing a majority of lipopolysaccharides in its outer leaflet. Genes controlled by the two-component regulatory system PhoPQ modify lipopolysaccharides. We isolate lipopolysaccharides from isogenic mutants of Salmonella sp., one lacking the modification, the other fully modified. These lipopolysaccharides were reconstituted as monolayers at the air-water interface, and their properties, as well as their interaction with a large lipophilic drug, novobiocin, was studied. X-ray reflectivity showed that the drug penetrated the monolayer of the unmodified lipopolysaccharides reaching the hydrophobic region, but was prevented from this penetration into the modified lipopolysaccharides. Results correlate with behavior of bacterial cells, which become resistant to antibiotics after PhoPQ-regulated modifications. Grazing incidence x-ray diffraction showed that novobiocin produced a striking increase in crystalline coherence length, and the size of the near-crystalline domains. PMID- 26682813 TI - Katanin Severing and Binding Microtubules Are Inhibited by Tubulin Carboxy Tails. AB - Microtubule dynamics in cells are regulated by associated proteins that can be either stabilizers or destabilizers. A class of destabilizers that is important in a large number of cellular activities is the microtubule-severing enzymes, yet little is known about how they function. Katanin p60 was the first ATPase associated with microtubule severing. Here, we investigate the activity of katanin severing using a GFP-labeled human version. We quantify the effect of katanin concentration on katanin binding and severing activity. We find that free tubulin can inhibit severing activity by interfering with katanin binding to microtubules. The inhibition is mediated by the sequence of the tubulin and specifically depends on the carboxy-terminal tails. We directly investigate the inhibition effect of tubulin carboxy-terminal tails using peptide sequences of alpha-, beta-, or detyrosinated alpha-tubulin tails that have been covalently linked to bovine serum albumin. Our results show that beta-tubulin tails are the most effective at inhibiting severing, and that detyrosinated alpha-tubulin tails are the least effective. These results are distinct from those for other severing enzymes and suggest a scheme for regulation of katanin activity in cells dependent on free tubulin concentration and the modification state of the tubulin. PMID- 26682814 TI - ATP Consumption of Eukaryotic Flagella Measured at a Single-Cell Level. AB - The motility of cilia and flagella is driven by thousands of dynein motors that hydrolyze adenosine triphosphate (ATP). Despite decades of genetic, biochemical, structural, and biophysical studies, some aspects of ciliary motility remain elusive, such as the regulation of beating patterns and the energetic efficiency of these nanomachines. In this study, we introduce an experimental method to measure ATP consumption of actively beating axonemes on a single-cell level. We encapsulated individual sea urchin sperm with demembranated flagellum inside water-in-oil emulsion droplets and measured the axoneme's ATP consumption by monitoring fluorescence intensity of a fluorophore-coupled reporter system for ATP turnover in the droplet. Concomitant phase contrast imaging allowed us to extract a linear dependence between the ATP consumption rate and the flagellar beating frequency, with ~2.3 * 10(5) ATP molecules consumed per beat of a demembranated flagellum. Increasing the viscosity of the aqueous medium led to modified beating waveforms of the axonemes and to higher energy consumption per beat cycle. Our single-cell experimental platform provides both new insights, to our knowledge, into the beating mechanism of flagella and a powerful tool for future studies. PMID- 26682815 TI - Molecular and Mechanical Causes of Microtubule Catastrophe and Aging. AB - Tubulin polymers, microtubules, can switch abruptly from the assembly to shortening. These infrequent transitions, termed "catastrophes", affect numerous cellular processes but the underlying mechanisms are elusive. We approached this complex stochastic system using advanced coarse-grained molecular dynamics modeling of tubulin-tubulin interactions. Unlike in previous simplified models of dynamic microtubules, the catastrophes in this model arise owing to fluctuations in the composition and conformation of a growing microtubule tip, most notably in the number of protofilament curls. In our model, dynamic evolution of the stochastic microtubule tip configurations over a long timescale, known as the system's "aging", gives rise to the nonexponential distribution of microtubule lifetimes, consistent with experiment. We show that aging takes place in the absence of visible changes in the microtubule wall or tip, as this complex molecular-mechanical system evolves slowly and asymptotically toward the steady state level of the catastrophe-promoting configurations. This new, to our knowledge, theoretical basis will assist detailed mechanistic investigations of the mechanisms of action of different microtubule-binding proteins and drugs, thereby enabling accurate control over the microtubule dynamics to treat various pathologies. PMID- 26682816 TI - Phosphorylating Titin's Cardiac N2B Element by ERK2 or CaMKIIdelta Lowers the Single Molecule and Cardiac Muscle Force. AB - Titin is a large filamentous protein that is responsible for the passive force of the cardiac sarcomere. Titin's force is generated by its I-band region, which includes the cardiac-specific N2B element. The N2B element consists of three immunoglobulin domains, two small unique sequence insertions, and a large 575 residue unique sequence, the N2B-Us. Posttranslational modifications of the N2B element are thought to regulate passive force, but the underlying mechanisms are unknown. Increased passive-force levels characterize diastolic stiffening in heart-failure patients, and it is critical to understand the underlying molecular mechanisms and identify therapeutic targets. Here, we used single-molecule force spectroscopy to study the mechanical effects of the kinases calcium/calmodulin dependent protein kinase II delta (CaMKIIdelta) and extracellular signal regulated kinase 2 (ERK2) on the single-molecule mechanics of the N2B element. Both CaMKIIdelta and ERK2 were found to phosphorylate the N2B element, and single molecule force spectroscopy revealed an increase in the persistence length (Lp) of the molecule, indicating that the bending rigidity of the molecule was increased. Experiments performed under oxidizing conditions and with a recombinant N2B element that had a simplified domain composition provided evidence that the Lp increase requires the N2B-Us of the N2B element. Mechanical experiments were also performed on skinned myocardium before and after phosphorylation. The results revealed a large (~30%) passive force reduction caused by CaMKIIdelta and a much smaller (~6%) reduction caused by ERK2. These findings support the notion that the important kinases ERK2 and CaMKIIdelta can alter the passive force of myocytes in the heart (although CaMKIIdelta appears to be more potent) during physiological and pathophysiological states. PMID- 26682817 TI - High-Affinity Interaction of the K-Ras4B Hypervariable Region with the Ras Active Site. AB - Ras proteins are small GTPases that act as signal transducers between cell surface receptors and several intracellular signaling cascades. They contain highly homologous catalytic domains and flexible C-terminal hypervariable regions (HVRs) that differ across Ras isoforms. KRAS is among the most frequently mutated oncogenes in human tumors. Surprisingly, we found that the C-terminal HVR of K Ras4B, thought to minimally impact the catalytic domain, directly interacts with the active site of the protein. The interaction is almost 100-fold tighter with the GDP-bound than the GTP-bound protein. HVR binding interferes with Ras-Raf interaction, modulates binding to phospholipids, and slightly slows down nucleotide exchange. The data indicate that contrary to previously suggested models of K-Ras4B signaling, HVR plays essential roles in regulation of signaling. High affinity binding of short peptide analogs of HVR to K-Ras active site suggests that targeting this surface with inhibitory synthetic molecules for the therapy of KRAS-dependent tumors is feasible. PMID- 26682818 TI - Flavin Binding to the Deca-heme Cytochrome MtrC: Insights from Computational Molecular Simulation. AB - Certain dissimilatory bacteria have the remarkable ability to use extracellular metal oxide minerals instead of oxygen as terminal electron sinks, using a process known as "extracellular respiration". Specialized multiheme cytochromes located on the outer membrane of the microbe were shown to be crucial for electron transfer from the cell surface to the mineral. This process is facilitated by soluble, biogenic flavins secreted by the organism for the purpose of acting as an electron shuttle. However, their interactions with the outer membrane cytochromes are not established on a molecular scale. Here, we study the interaction between the outer-membrane deca-heme cytochrome MtrC from Shewanella oneidensis and flavin mononucleotide (FMN in fully oxidized quinone form) using computational docking. We find that interaction of FMN with MtrC is significantly weaker than with known FMN-binding proteins, but identify a mildly preferred interaction site close to heme 2 with a dissociation constant (Kd) = 490 MUM, in good agreement with recent experimental estimates, Kd = 255 MUM. The weak interaction with MtrC can be qualitatively explained by the smaller number of hydrogen bonds that the planar headgroup of FMN can form with this protein compared to FMN-binding proteins. Molecular dynamics simulation gives indications for a possible conformational switch upon cleavage of the disulphide bond of MtrC, but without concomitant increase in binding affinities according to this docking study. Overall, our results suggest that binding of FMN to MtrC is reversible and not highly specific, which may be consistent with a role as redox shuttle that facilitates extracellular respiration. PMID- 26682819 TI - Single-Molecule FRET Reveals Three Conformations for the TLS Domain of Brome Mosaic Virus Genome. AB - Metabolite-dependent conformational switching in RNA riboswitches is now widely accepted as a critical regulatory mechanism for gene expression in bacterial systems. More recently, similar gene regulation mechanisms have been found to be important for viral systems as well. One of the most abundant and best-studied systems is the tRNA-like structure (TLS) domain, which has been found to occur in many plant viruses spread across numerous genera. In this work, folding dynamics for the TLS domain of Brome Mosaic Virus have been investigated using single molecule fluorescence resonance energy transfer techniques. In particular, burst fluorescence methods are exploited to observe metal-ion ([M(n+)])-induced folding in freely diffusing RNA constructs resembling the minimal TLS element of brome mosaic virus RNA3. The results of these experiments reveal a complex equilibrium of at least three distinct populations. A stepwise, or consecutive, thermodynamic model for TLS folding is developed, which is in good agreement with the [M(n+)] dependent evolution of conformational populations and existing structural information in the literature. Specifically, this folding pathway explains the metal-ion dependent formation of a functional TLS domain from unfolded RNAs via two consecutive steps: 1) hybridization of a long-range stem interaction, followed by 2) formation of a 3'-terminal pseudoknot. These two conformational transitions are well described by stepwise dissociation constants for [Mg(2+)] (K1 = 328 +/- 30 MUM and K2 = 1092 +/- 183 MUM) and [Na(+)] (K1 = 74 +/- 6 mM and K2 = 243 +/- 52 mM)-induced folding. The proposed thermodynamic model is further supported by inhibition studies of the long-range stem interaction using a complementary DNA oligomer, which effectively shifts the dynamic equilibrium toward the unfolded conformation. Implications of this multistep conformational folding mechanism are discussed with regard to regulation of virus replication. PMID- 26682820 TI - Doubly Spin-Labeled RNA as an EPR Reporter for Studying Multicomponent Supramolecular Assemblies. AB - mRNAs are involved in complicated supramolecular complexes with human 40S and 80S ribosomes responsible for the protein synthesis. In this work, a derivative of nonaribonucleotide pUUCGUAAAA with nitroxide spin labels attached to the 5' phosphate and to the C8 atom of the adenosine in sixth position (mRNA analog) was used for studying such complexes using double electron-electron resonance/pulsed electron-electron double resonance spectroscopy. The complexes were assembled with participation of tRNA(Phe), which targeted triplet UUC of the derivative to the ribosomal peptidyl site and predetermined location of the adjacent GUA triplet coding for Val at the aminoacyl (A) site. The interspin distances were measured between the two labels of mRNA analog attached to the first nucleotide of the peptidyl site bound codon and to the third nucleotide of the A site bound codon, in the absence/presence of second tRNA bound at the A site. The values of the obtained interspin distances agree with those calculated for available near atomic structures of similar complexes of 40S and 80S ribosomes, showing that neither 60S subunit nor tRNA at the A site have a noticeable effect on arrangement of mRNA at the codon-anticodon interaction area. In addition, the shapes of distance distributions in four studied ribosomal complexes allowed conclusions on conformational flexibility of mRNA in these complexes. Overall, the results of this study are the first, to our knowledge, demonstration of double electron-electron resonance/pulsed electron-electron double resonance application for measurements of intramolecular distances in multicomponent supramolecular complexes involving intricate cellular machineries and for evaluating dynamic properties of ligands bound to these machineries. PMID- 26682821 TI - Tuning RNA Flexibility with Helix Length and Junction Sequence. AB - The increasing awareness of RNA's central role in biology calls for a new understanding of how RNAs, like proteins, recognize biological partners. Because RNA is inherently flexible, it assumes a variety of conformations. This conformational flexibility can be a critical aspect of how RNA attracts and binds molecular partners. Structurally, RNA consists of rigid basepaired duplexes, separated by flexible non-basepaired regions. Here, using an RNA system consisting of two short helices, connected by a single-stranded (non-basepaired) junction, we explore the role of helix length and junction sequence in determining the range of conformations available to a model RNA. Single-molecule Forster resonance energy transfer reports on the RNA conformation as a function of either mono- or divalent ion concentration. Electrostatic repulsion between helices dominates at low salt concentration, whereas junction sequence effects determine the conformations at high salt concentration. Near physiological salt concentrations, RNA conformation is sensitive to both helix length and junction sequence, suggesting a means for sensitively tuning RNA conformations. PMID- 26682822 TI - Predicting 3D Structure, Flexibility, and Stability of RNA Hairpins in Monovalent and Divalent Ion Solutions. AB - A full understanding of RNA-mediated biology would require the knowledge of three dimensional (3D) structures, structural flexibility, and stability of RNAs. To predict RNA 3D structures and stability, we have previously proposed a three-bead coarse-grained predictive model with implicit salt/solvent potentials. In this study, we further develop the model by improving the implicit-salt electrostatic potential and including a sequence-dependent coaxial stacking potential to enable the model to simulate RNA 3D structure folding in divalent/monovalent ion solutions. The model presented here can predict 3D structures of RNA hairpins with bulges/internal loops (<77 nucleotides) from their sequences at the corresponding experimental ion conditions with an overall improved accuracy compared to the experimental data; the model also makes reliable predictions for the flexibility of RNA hairpins with bulge loops of different lengths at several divalent/monovalent ion conditions. In addition, the model successfully predicts the stability of RNA hairpins with various loops/stems in divalent/monovalent ion solutions. PMID- 26682823 TI - Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I Domain by Urea Binding. AB - The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining (3)JNC' couplings transmitted through H-bonds, the temperature and urea-concentration dependence of (1)HN and (15)N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded beta-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short alpha-helix and three-stranded beta-sheet. H-bonds, separately determined from solvent protection and (3)JNC' H-bond couplings, are identified with an accuracy of 90% by (1)HN temperature coefficients. The accuracy is improved to 95% when (15)N temperature coefficients are also included. In contrast, the urea dependence of (1)HN and (15)N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. PMID- 26682824 TI - Intracochlear Scala Media Pressure Measurement: Implications for Models of Cochlear Mechanics. AB - Models of the active cochlea build upon the underlying passive mechanics. Passive cochlear mechanics is based on physical and geometrical properties of the cochlea and the fluid-tissue interaction between the cochlear partition and the surrounding fluid. Although the fluid-tissue interaction between the basilar membrane and the fluid in scala tympani (ST) has been explored in both active and passive cochleae, there was no experimental data on the fluid-tissue interaction on the scala media (SM) side of the partition. To this aim, we measured sound evoked intracochlear pressure in SM close to the partition using micropressure sensors. All the SM pressure data are from passive cochleae, likely because the SM cochleostomy led to loss of endocochlear potential. Thus, these experiments are studies of passive cochlear mechanics. SM pressure close to the tissue showed a pattern of peaks and notches, which could be explained as an interaction between fast and slow (i.e., traveling wave) pressure modes. In several animals SM and ST pressure were measured in the same cochlea. Similar to previous studies, ST-pressure was dominated by a slow, traveling wave mode at stimulus frequencies in the vicinity of the best frequency of the measurement location, and by a fast mode above best frequency. Antisymmetric pressure between SM and ST supported the classic single-partition cochlear models, or a dual-partition model with tight coupling between partitions. From the SM and ST pressure we calculated slow and fast modes, and from active ST pressure we extrapolated the passive findings to the active case. The passive slow mode estimated from SM and ST data was low-pass in nature, as predicted by cochlear models. PMID- 26682825 TI - Micromechanical Modeling Study of Mechanical Inhibition of Enzymatic Degradation of Collagen Tissues. AB - This study investigates how the collagen fiber structure influences the enzymatic degradation of collagen tissues. We developed a micromechanical model of a fibrous collagen tissue undergoing enzymatic degradation based on two central hypotheses. The collagen fibers are crimped in the undeformed configuration. Enzymatic degradation is an energy activated process and the activation energy is increased by the axial strain energy density of the fiber. We determined the intrinsic degradation rate and characteristic energy for mechanical inhibition from fibril-level degradation experiments and applied the parameters to predict the effect of the crimped fiber structure and fiber properties on the degradation of bovine cornea and pericardium tissues under controlled tension. We then applied the model to examine the effect of the tissue stress state on the rate of tissue degradation and the anisotropic fiber structures that developed from enzymatic degradation. PMID- 26682826 TI - Sympathetic regulation of blood pressure in normotension and hypertension: when sex matters. AB - NEW FINDINGS: What is the topic of this review? Hypertension is a major problem in Western society. Risk of hypertension increases with age, especially in women, who have lower risk compared with men until menopause. This review outlines the sex differences in the sympathetic control of blood pressure and how these mechanisms change with age. What advances does it highlight? It has recently been recognized that men and women regulate blood pressure by different physiological mechanisms. This is important for both the understanding and the clinical management of individual patients with hypertension. This review summarizes recent advances in understanding how the regulation of blood pressure in hypertension by the sympathetic nervous system differs between men and women. The sympathetic nervous system has a central role in the regulation of arterial blood pressure (BP) and in the development of hypertension in humans. Recent evidence points to differences between the sexes in the integrative mechanisms by which BP is controlled, suggesting that the development of hypertension may follow distinct pathways in women compared with men. An important aspect of sympathetic control of BP is its substantial interindividual variability. In healthy young men, the variability in sympathetic nerve activity (SNA) is balanced by variability in cardiac output and vascular adrenergic responses, such that BP remains similar, and normal, across a severalfold range of resting SNA values. In young women, variability in resting SNA is similar to that seen in men, but the 'balancing' mechanisms are strikingly different; women exhibit greater beta adrenergic vasodilatation compared with men, which minimizes the pressor effects of a given level of SNA. Ageing is associated with increased SNA and a loss of the balancing factors seen in younger people, leading to an increased risk of hypertension in older people. Loss of oestrogen with menopause in women appears to be linked mechanistically with the decrease in beta-adrenergic vasodilatation and the increased risk of hypertension in older women. Other important factors contributing to hypertension via sympathetic mechanisms are obesity and arterial stiffening, both of which increase with ageing. We conclude with a discussion of important areas in which more work is needed to understand and manage appropriately the sex-specific mechanisms in the development and maintenance of hypertension. PMID- 26682827 TI - The use of serial outpatient complete blood count (CBC) results to derive biologic variation: a new tool to gauge the acceptability of hematology testing. AB - INTRODUCTION: Most estimates of biologic variation (sb ) are based on periodically acquiring and storing specimens from reference subjects, followed by analysis within a tightly controlled analytic run. We demonstrate that reliable estimates of sb can be derived for virtually all constituents of the CBC from previously obtained paired patient results and summary QC data. METHODS: A laboratory data repository provided all of the outpatient CBC results measured over 20.5 months at a large Canadian referral laboratory. These CBC measurements were taken on one of four Beckman Coulter LH analyzers. A total of 1852 different patients had CBCs repeated at least twice within 84 h. We tabulated the pairs of intrapatient constituents that were separated by 0-6, 6-12, 12-18,... 72-78, and 78-84 h. The standard deviations of duplicates (SDD) of the paired data were then regressed against time. The y-intercept represents the sum of sb and short-term analytic variation (sa ): y0 =(s(2) a +s(2) b )(1/2) . The short-term imprecision was determined from normal range Coulter quality control specimens. RESULTS: Patient sb for hematocrit, MCH, absolute monocytes, and absolute neutrophils are extremely close to those determined by biologic variation experiments using healthy volunteers. Most of the other estimates of sb tended to be slightly lower than literature estimates. CONCLUSIONS: We describe a novel approach to deriving sb . The ratio of the sb to sa (a measure of sigma) indicates that the Beckman Coulter LH is extremely suitable for CBC monitoring of outpatients as well as for inpatients, whose sb is generally higher. PMID- 26682828 TI - Correlates of interpersonal dependency and detachment in an adolescent inpatient sample. AB - Interpersonal dependency has been linked to psychological distress, depression, help seeking, treatment compliance, and sensitivity to interpersonal cues in adult samples. However, there is a dearth of research focusing on dependency in child and adolescent samples. The current study examined the construct validity of a measure of interpersonal dependency. The authors investigated how interpersonal dependency and detachment relate to behavioral problems, subjective well-being, interpersonal problems, and global symptom severity in adolescent inpatients. Destructive overdependence (DO) and dysfunctional detachment (DD) were positively related to interpersonal distress, behavioral problems, and symptom severity and negatively related to psychological health and well-being. Healthy dependency (HD) was associated with fewer behavioral problems and less symptom severity and positively related to subjective well-being. The clinical implications of these findings are discussed. PMID- 26682829 TI - Neuropsychological functioning and profile validity on the Personality Assessment Inventory (PAI): An investigation in multiple psychiatric settings. AB - Psychologists in medical settings are frequently tasked with providing comprehensive evaluations of patients with complex medical and psychiatric conditions. In order to achieve these aims, standardized measures of neurocognitive and psychological functioning are often employed to empirically assess a patient's level of functioning across an array of relevant clinical domains. However, less is known about the degree to which cognitive impairment affects a patient's ability to complete these more comprehensive assessments, raising questions about test validity. The current study sought to contribute to this growing body of literature by examining whether neurocognitive functioning is associated with profile validity on the Personality Assessment Inventory (PAI) in both outpatient (N = 321) and inpatient (N = 131) psychiatric settings. In Study 1, results indicate that while multiple cognitive domains are associated with overall profile validity in psychiatric outpatients, attentional impairment specifically was found to be a significant predictor of profile invalidity after accounting for the effects of overall intellectual functioning (accounting for 13% of the variance overall). The magnitude of attentional impairment specifically, and number of impaired cognitive domains more generally, were also found to be meaningfully associated with overall profile validity. Likewise, in Study 2, PAI profile validity was found to be meaningfully associated with gross cognitive impairment on the WMS-IV Brief Cognitive Status Examination (BCSE) in an inpatient psychiatric setting, with almost half of the patients in the most impaired group yielding invalid PAI profiles. The clinical implications of these findings are discussed. PMID- 26682830 TI - The Computerized Implicit Representation Test: Construct and incremental validity. AB - Discrepancies in mental representations between self-aspects and significant others are associated with depression, personality disorders, emotional reactivity, and interpersonal distress. The Computerized Implicit Representation Test (CIRT) is a novel measure developed to assess discrepancies in mental representations. Inpatient participants (N = 165) enrolled in a longitudinal study completed baseline CIRT ratings of similarity between self-aspects (actual self, ideal-self, and ought-self) and between actual-self and significant others (mother, father, liked others, and disliked others). Based on the similarity ratings, multidimensional scaling was utilized to generate distances between key self- and other representations in three-dimensional space. Results of univariate linear regression analyses demonstrated that discrepancies (distances) between self-aspects, actual-self to others, and actual-self to mother were significantly associated with impulsive and self-destructive behaviors and/or lifetime anxiety disorders. Multivariate hierarchical linear regression models further indicated that three CIRT variables provided incremental validity above and beyond age, gender, and/or borderline personality disorder. PMID- 26682831 TI - Commentary on Kim et al., Effects of therapeutic relationship, expectancy, and credibility in breathing therapies for anxiety. AB - Kim and colleagues (2015) explored influences on clinical outcomes related to nonspecific therapeutic factors, addressing the importance of client expectancy and development of the therapeutic alliance. In the process, however, the authors carry forward conclusions from their prior research on treatment of panic that two opposing breathing retraining protocols are equally effective. Neither the experimental design nor the sample size of the current or previous study warrants reaching those conclusions. This commentary examines the findings of the current and previous studies and points to consistent trends that suggest that breathing retraining of panic patients may be enhanced by protocols aimed at raising exhaled CO2. PMID- 26682833 TI - Abdominal varicosities secondary to inferior vena cava filter thrombosis. PMID- 26682834 TI - Gallstone ileus of the sigmoid colon: an extremely rare cause of large bowel obstruction detected by multiplanar CT. AB - Gallstone ileus of the sigmoid colon is an important, though extremely rare, cause of large bowel obstruction. The gallstone often enters the large bowel through a fistula formation between the gallbladder and colon, and impacts at a point of narrowing, causing large bowel obstruction. We describe the case of an 80-year-old woman who presented with features of bowel obstruction. Multiplanar abdominal CT demonstrated a cholecystocolonic fistula in exquisite detail. The scan also showed obstruction of the colon due to a large gallstone impacted just proximal to a stricture in the sigmoid. Owing to inflammatory adhesions and a stricture from extensive diverticular disease, the gallstone could not be retrieved. This frail and elderly woman was treated with a loop colostomy to relieve bowel obstruction. The patient made an uneventful recovery. PMID- 26682835 TI - Unusual cause for gum hypertrophy and skin nodules in a child. AB - Juvenile hyaline fibromatosis (JHF) is a rare progressive autosomal recessive disease that is characterised by papulonodular skin lesions, soft tissue masses, joint contractures, gingival hypertrophy and osteolytic bone lesions. We present an 18-month-old boy with JHF. This case demonstrates that JHF should be considered in the differential diagnosis when multiple subcutaneous nodules are observed in the face, head and neck. Gum hypertrophy with palatal nodules is unusual in JHF. PMID- 26682836 TI - Natal teeth in premature dizygotic twin girls. AB - Presence or eruption of teeth immediately at or after birth is a rarely reported phenomenon. This condition is referred to as natal teeth, neonatal teeth, congenital teeth, fetal teeth, predeciduous teeth and dentitia praecox. The most affected teeth are lower primary central incisors with the incidence of 1:2000 for natal and 1:3500 for neonatal teeth. The aetiology of this anomaly is still not clear, however, attributes have been reported in relation to congenital teeth, multiple factors and some syndromes. The management of such cases depends on clinical characteristics of natal or neonatal teeth, as well as complications that they might cause. The aim of this paper is to discuss a rare case of occurrence of two natal teeth in both premature dizygotic twin female babies with specific emphasis on the literature review related to concerns regarding prevalence, aetiology, clinical characteristics, differential diagnosis, complications and management. PMID- 26682837 TI - Difficult diagnosis: internal herniation of the terminal ileum through the foramen of Winslow into the lesser sac. AB - Herniation of the bowel through the foramen of Winslow is rare and accounts for 8% of all internal herniae. It typically presents clinically and biochemically as small bowel obstruction. It carries a high mortality as diagnosis is often delayed, despite bowel strangulation, as clinical signs are not typical and imaging may not be diagnostic. In the case presented here, a healthy 25-year-old man was admitted with sudden onset right-sided abdominal and back pain. He denied vomiting, and had opened his bowels. His bloods were normal and venous lactate <2; CT was not diagnostic. At laparotomy, he was found to have internal herniation of the terminal ileum through the foramen of Winslow, which was gangrenous and required resection. This paper discusses the difficulty in diagnosing internal herniation and poses the question as to whether we are too dependent on CT findings in the setting of an acute abdomen. PMID- 26682838 TI - Aplasia of the lung in a neonate--the myth is explored. AB - A term appropriate for gestational age baby boy was delivered by lower segment caesarean section. The baby was antenatally diagnosed with resolving cystic adenomatoid malformation. At birth, he developed respiratory distress requiring active resuscitation and later was diagnosed to have right lung aplasia, managed with respiratory support. He gradually improved and was discharged home on room air. PMID- 26682839 TI - Dapsone hypersensitivity syndrome not related to G6PD deficiency. AB - Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life threatening reaction to dapsone. We describe a 55-year-old Caucasian woman with normal glucose-6-phosphate dehydrogenase levels presenting with an extensive skin eruption, high-grade fever, pneumonitis and hepatitis, which occurred within 3 weeks after initiation of dapsone. In addition to supportive care, the patient was successfully treated with high-dose corticosteroids and antibiotics. The combination of high-grade fever, skin rash, lung and liver involvement made a dapsone hypersensitivity syndrome very likely. PMID- 26682840 TI - Cryptococcal eosinophilic meningitis in a patient with sarcoidosis. AB - A 51-year-old African-American man with underlying pulmonary, hepatic and splenic sarcoidosis, reported a 3-day history of headache, neck stiffness and photophobia. He was not using medication for chronic sarcoidosis. Physical examination was significant for nuchal rigidity. Lumbar puncture revealed marked eosinophilia in the cerebrospinal fluid, which, on further analysis, demonstrated a positive cryptococcal antigen. HIV antibody and PCR tests were negative. Bronchoscopy and fungal blood cultures were also negative. The patient was started on amphotericin B and flucytosine, with significant clinical improvement. He recovered well without any neurological sequelae and remained symptom-free at 2-week follow-up. Cryptococcal central nervous infections are uniformly fatal if left untreated. Prompt diagnosis and treatment is essential, to prevent the associated high morbidity and mortality. PMID- 26682841 TI - Under seize: neurocysticercosis in an immigrant woman and review of a growing neglected disease. AB - Neurocysticercosis (NCC) is a significantly neglected tropical disease and, with increasing globalisation, a notable emerging infection in the developed world. We describe a case of ventricular NCC in a 22-year-old Mexican-American woman with a history of seizures, who presented with 2 weeks of headaches and intermittent fevers progressing to altered mental status and vomiting. Initial imaging revealed a cystic mass at the posteroinferior aspect of the third ventricle superior to the aqueduct of Sylvius, calcifications scattered throughout the parenchyma, and enlargement of the lateral and third ventricles. Initial laboratories were unrevealing and serum investigations for Taenia solium antibody were negative, but T. solium antibody was subsequently returned positive from cerebrospinal fluid. This case highlights important issues regarding the clinical presentation, diagnostic evaluation and treatment of NCC relevant to providers not only in areas with endemic disease but, importantly, in locales with diverse immigrant populations. PMID- 26682842 TI - Ziv-aflibercept: a novel option for the treatment of polypoidal choroidal vasculopathy. AB - Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy usually treated using photodynamic therapy (PDT) and antivascular endothelial growth factor agents. However, these cases may sometimes be refractory to both PDT and ranibizumab or bevacizumab, and may have persistent intra-retinal fluid. Recently, studies have reported that aflibercept may be effective in such resistant cases. However, high cost and limited availability has restricted its use to only a few countries. Ziv-aflibercept (Zaltrap), a systemic analogue of aflibercept, has been tried recently and it has been effective in macular oedema. We report a case of PCV resistant to PDT and ranibizumab, which responded well to intravitreal ziv-aflibercept. PMID- 26682843 TI - Ovarian vein thrombosis in a polytrauma patient. AB - A young mother presented to a major trauma centre following a road traffic collision. Her admission CT traumagram demonstrated liver and renal lacerations, spinal and pelvic fractures with no abnormalities of the ovarian veins. Her inpatient course was uncomplicated other than a sustained, isolated raised C reactive protein. CT of the abdomen 1 week after injury demonstrated stable solid organ injuries and the additional, unexpected finding of a right ovarian vein thrombosis (OVT). A pragmatic approach was taken towards the management of the OVT given the haemorrhagic risk from her traumatic injuries. A multidisciplinary, consultant-led plan was made to slowly increase enoxaparin to a therapeutic dose under close surveillance and to then switch to warfarin following an outpatient consultation with a consultant haematologist. A MR venogram was performed after 3 months of anticoagulation, and this demonstrated complete resolution of the OVT and normal appearances of the ovary. PMID- 26682844 TI - A young man with extensor eruptive skin lesions. PMID- 26682845 TI - Angioleiomyoma of the larynx: beware the subglottic lesion. AB - Angioleiomyomas are a benign group of tumours rarely documented in the head and neck region. We present a case of a 47-year-old man attending the ear, nose and throat outpatient clinic, with a history of hoarseness over many years. Investigation revealed a left-sided subglottic lesion. He underwent microlaryngoscopy and biopsy, and the lesion was sent for histological analysis. Postoperatively, the patient began to expectorate fresh red blood that continued for several hours, requiring surgical intervention. Haemostatic control was achieved and a tracheostomy was sited for airway protection. Histopathology identified angioleiomyoma as the cause of his symptoms. Following multidisciplinary team discussion, this was managed with injection of bleomycin and subsequent surgical excision. This case is a reminder that subglottic lesions are often vascular in nature, and should be investigated with imaging and angiography prior to surgery, to avoid complications. PMID- 26682846 TI - Unusual pattern of neonatal hyperhidrosis. PMID- 26682847 TI - Comparison of 1-Day Emergency Department Observation and Inpatient Ward for 1-Day Admissions in Syncope Patients. AB - BACKGROUND: In an era of increasing health care costs, the need for hospitalization is being scrutinized. In particular, 1-day hospitalizations are thought to be especially costly and unnecessary, and, increasingly, emergency department observation units (EDOUs) are being used as alternatives. OBJECTIVE: Our aim was to determine the differences in outcomes and diagnoses between 1-day inpatient and EDOU stays for syncope. METHODS: We retrospectively reviewed a cohort of patients with syncope who were seen in an urban ED with 1-day admission to an inpatient ward, EDOU, or full hospitalization. Etiology of syncope was classified as benign (vasovagal, dehydration), serious (dysrhythmia, sepsis, stroke/intracranial bleed, hemorrhage, valvular, ischemia, pulmonary embolism), or unknown. Data were analyzed using Fisher's exact test and t-test. RESULTS: One hundred and seventy-two of 351 patients were >1-day admissions, 152 (85%) were admitted for 1 day, and 27 (15%) were admitted to EDOU. The mean (standard deviation [SD]) age when admitted to the hospital was significantly higher at 72 (18.4) years for > 1-day admissions and 68.8 (19.6) years for 1-day admissions vs. 53.0 (18.9) years for EDOU patients (p < 0.01). For fully admitted patients, 36% had benign etiologies of syncope and 38% had serious causes of syncope; in 1 day admitted patients, 48% had benign etiologies and 14% had serious causes. Among EDOU patients, 44% had benign etiologies and none were serious. One-day patients were more likely to have unknown causes of syncope at discharge (36%; 95% confidence interval 0.28 to 0.43) when compared with admitted patients (26%; 95% CI 0.2 to 0.33); similarly, observation patients were more likely to be discharged without a diagnosis (56%; 95% CI 0.37 to 0.74; p <= 0.05). CONCLUSIONS: EDOU patients were less likely than patients admitted to the hospital to be discharged with an etiology of their syncope. Future EDOU protocols can benefit from set admission criteria and standardized evaluation protocols to facilitate maximal use of EDOU for syncope. PMID- 26682848 TI - Epilepsy with temporal encephalocele: Characteristics of electrocorticography and surgical outcome. AB - Temporal lobe encephaloceles (TEs) are increasingly identified in patients with epilepsy due to advances in neuroimaging. Select patients become seizure-free with lesionectomy. In practice, however, many of these patients will undergo standard anterior temporal lobectomy. Herein we report on the first series of patients with refractory temporal lobe epilepsy (TLE) with encephalocele to undergo chronic or intraoperative electrocorticography (ECoG) in order to characterize the putative epileptogenic nature of these lesions and help guide surgical planning. This retrospective study includes nine adult patients with magnetic resonance imaging/computed tomography (MRI/CT)-defined temporal encephalocele treated between 2007 and 2014 at University of California San Francisco (UCSF). Clinical features, ECoG, imaging, and surgical outcomes are reviewed. Six patients underwent resective epilepsy surgery. Each case demonstrated abnormal epileptiform discharges around the cortical area of the encephalocele. Two underwent tailored lesionectomy and four underwent lesionectomy plus anterior medial temporal resection. Postoperatively, five patients, including both with lesionectomy only, had Engel class Ia surgical outcome, and one had a class IIb surgical outcome. The role of TE in the pathogenesis of epilepsy is uncertain. ECoG can confirm the presence of interictal epileptiform discharges and seizures arising from these lesions. Patients overall had a very good surgical prognosis, even with selective surgical approaches. PMID- 26682849 TI - Chirality Matters: Synthesis and Consumption of the d-Enantiomer of Lactic Acid by Synechocystis sp. Strain PCC6803. AB - Both enantiomers of lactic acid, l-lactic acid and d-lactic acid, can be produced in a sustainable way by a photosynthetic microbial cell factory and thus from CO2, sunlight, and water. Several properties of polylactic acid (a polyester of polymerized lactic acid) depend on the controlled blend of these two enantiomers. Recently, cyanobacterium Synechocystis sp. strain PCC6803 was genetically modified to allow formation of either of these two enantiomers. This report elaborates on the d-lactic acid production achieved by the introduction of a d specific lactate dehydrogenase from the lactic acid bacterium Leuconostoc mesenteroides into Synechocystis. A typical batch culture of this recombinant strain initially shows lactic acid production, followed by a phase of lactic acid consumption, until production "outcompetes" consumption at later growth stages. We show that Synechocystis is able to use d-lactic acid, but not l-lactic acid, as a carbon source for growth. Deletion of the organism's putative d-lactate dehydrogenase (encoded by slr1556), however, does not eliminate this ability with respect to d-lactic acid consumption. In contrast, d-lactic acid consumption does depend on the presence of glycolate dehydrogenase GlcD1 (encoded by sll0404). Accordingly, this report highlights the need to match a product of interest of a cyanobacterial cell factory with the metabolic network present in the host used for its synthesis and emphasizes the need to understand the physiology of the production host in detail. PMID- 26682850 TI - Distributions of Fecal Markers in Wastewater from Different Climatic Zones for Human Fecal Pollution Tracking in Australian Surface Waters. AB - Recreational and potable water supplies polluted with human wastewater can pose a direct health risk to humans. Therefore, sensitive detection of human fecal pollution in environmental waters is very important to water quality authorities around the globe. Microbial source tracking (MST) utilizes human fecal markers (HFMs) to detect human wastewater pollution in environmental waters. The concentrations of these markers in raw wastewater are considered important because it is likely that a marker whose concentration is high in wastewater will be more frequently detected in polluted waters. In this study, quantitative PCR (qPCR) assays were used to determine the concentrations of fecal indicator bacteria (FIB) Escherichia coli and Enterococcus spp., HFMs Bacteroides HF183, human adenoviruses (HAdVs), and polyomaviruses (HPyVs) in raw municipal wastewater influent from various climatic zones in Australia. E. coli mean concentrations in pooled human wastewater data sets (from various climatic zones) were the highest (3.2 * 10(6) gene copies per ml), followed by those of HF183 (8.0 * 10(5) gene copies per ml) and Enterococcus spp. (3.6 * 10(5) gene copies per ml). HAdV and HPyV concentrations were 2 to 3 orders of magnitude lower than those of FIB and HF183. Strong positive and negative correlations were observed between the FIB and HFM concentrations within and across wastewater treatment plants (WWTPs). To identify the most sensitive marker of human fecal pollution, environmental water samples were seeded with raw human wastewater. The results from the seeding experiments indicated that Bacteroides HF183 was more sensitive for detecting human fecal pollution than HAdVs and HPyVs. Since the HF183 marker can occasionally be present in nontarget animal fecal samples, it is recommended that HF183 along with a viral marker (HAdVs or HPyVs) be used for tracking human fecal pollution in Australian environmental waters. PMID- 26682851 TI - Genetic Analysis Reveals the Essential Role of Nitrogen Phosphotransferase System Components in Sinorhizobium fredii CCBAU 45436 Symbioses with Soybean and Pigeonpea Plants. AB - The nitrogen phosphotransferase system (PTS(Ntr)) consists of EI(Ntr), NPr, and EIIA(Ntr). The active phosphate moiety derived from phosphoenolpyruvate is transferred through EI(Ntr) and NPr to EIIA(Ntr). Sinorhizobium fredii can establish a nitrogen-fixing symbiosis with the legume crops soybean (as determinate nodules) and pigeonpea (as indeterminate nodules). In this study, S. fredii strains with mutations in ptsP and ptsO (encoding EI(Ntr) and NPr, respectively) formed ineffective nodules on soybeans, while a strain with a ptsN mutation (encoding EIIA(Ntr)) was not defective in symbiosis with soybeans. Notable reductions in the numbers of bacteroids within each symbiosome and of poly-beta-hydroxybutyrate granules in bacteroids were observed in nodules infected by the ptsP or ptsO mutant strains but not in those infected with the ptsN mutant strain. However, these defects of the ptsP and ptsO mutant strains were recovered in ptsP ptsN and ptsO ptsN double-mutant strains, implying a negative role of unphosphorylated EIIA(Ntr) in symbiosis. Moreover, the symbiotic defect of the ptsP mutant was also recovered by expressing EI(Ntr) with or without the GAF domain, indicating that the putative glutamine-sensing domain GAF is dispensable in symbiotic interactions. The critical role of PTS(Ntr) in symbiosis was also observed when related PTS(Ntr) mutant strains of S. fredii were inoculated on pigeonpea plants. Furthermore, nodule occupancy and carbon utilization tests suggested that multiple outputs could be derived from components of PTS(Ntr) in addition to the negative role of unphosphorylated EIIA(Ntr). PMID- 26682852 TI - Intracellular and Extracellular Expression of Bacillus thuringiensis Crystal Protein Cry5B in Lactococcus lactis for Use as an Anthelminthic. AB - The Bacillus thuringiensis crystal (Cry) protein Cry5B (140 kDa) and a truncated version of the protein, tCry5B (79 kDa), are lethal to nematodes. Genes encoding the two proteins were separately cloned into a high-copy-number vector with a strong constitutive promoter (pTRK593) in Lactococcus lactis for potential oral delivery against parasitic nematode infections. Western blots using a Cry5B specific antibody revealed that constitutively expressed Cry5B and tCry5B were present in both cells and supernatants. To increase production, cry5B was cloned into the high-copy-number plasmid pMSP3535H3, carrying a nisin-inducible promoter. Immunoblotting revealed that 3 h after nisin induction, intracellular Cry5B was strongly induced at 200 ng/ml nisin, without adversely affecting cell viability or cell membrane integrity. Both Cry5B genes were also cloned into plasmid pTRK1061, carrying a promoter and encoding a transcriptional activator that invoke low-level expression of prophage holin and lysin genes in Lactococcus lysogens, resulting in a leaky phenotype. Cry5B and tCry5B were actively expressed in the lysogenic strain L. lactis KP1 and released into cell supernatants without affecting culture growth. Lactate dehydrogenase (LDH) assays indicated that Cry5B, but not LDH, leaked from the bacteria. Lastly, using intracellular lysates from L. lactis cultures expressing both Cry5B and tCry5B, in vivo challenges of Caenorhabditis elegans worms demonstrated that the Cry proteins were biologically active. Taken together, these results indicate that active Cry5B proteins can be expressed intracellularly in and released extracellularly from L. lactis, showing potential for future use as an anthelminthic that could be delivered orally in a food-grade microbe. PMID- 26682853 TI - Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica. AB - The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular beta-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID- 26682854 TI - Identification of Unknown Carboxydovore Bacteria Dominant in Deciduous Forest Soil via Succession of Bacterial Communities, coxL Genotypes, and Carbon Monoxide Oxidation Activity in Soil Microcosms. AB - Surveys of the coxL gene, encoding the large subunit of the CO dehydrogenase, are used as a standard approach in ecological studies of carboxydovore bacteria scavenging atmospheric CO. Recent soil surveys unveiled that the distribution of coxL sequences encompassing the atypical genotype coxL type I group x was correlated to the CO oxidation activity. Based on phylogenetic analysis including the available coxL reference genome sequences, this unusual genotype was assigned to an unknown member of the Deltaproteobacteria, with the coxL sequence from Haliangium ochraceum being the sole and closest reference sequence. Here we seek to challenge the proposed taxonomic assignation of the coxL group x genotype through the monitoring of CO consumption activity and microbial community successions during the colonization of sterile soil microcosms inoculated with indigenous microorganisms. In our study, we established that the estimated population density of Deltaproteobacteria was too small to account for the abundance of the coxL group x genotype detected in soil. Furthermore, we computed a correlation network to relate 16S rRNA gene profiles with the succession of coxL genotypes and CO uptake activity in soil. We found that most of the coxL genotypes for which the colonization profile displayed covariance with CO uptake activity were related to potential carboxydovore bacteria belonging to Actinobacteria and Alphaproteobacteria. Our analysis did not provide any evidence that coxL group x genotypes belonged to Deltaproteobacteria. Considering the colonization profile of CO-oxidizing bacteria and the theoretical energy yield of measured CO oxidation rates in soil microcosms, we propose that unknown carboxydovore bacteria harboring the atypical coxL group x genotype are mixotrophic K-strategists. PMID- 26682855 TI - Ectomycorrhizal Fungal Protein Degradation Ability Predicted by Soil Organic Nitrogen Availability. AB - In temperate and boreal forest ecosystems, nitrogen (N) limitation of tree metabolism is alleviated by ectomycorrhizal (ECM) fungi. As forest soils age, the primary source of N in soil switches from inorganic (NH4 (+) and NO3 (-)) to organic (mostly proteins). It has been hypothesized that ECM fungi adapt to the most common N source in their environment, which implies that fungi growing in older forests would have greater protein degradation abilities. Moreover, recent results for a model ECM fungal species suggest that organic N uptake requires a glucose supply. To test the generality of these hypotheses, we screened 55 strains of 13 Suillus species with different ecological preferences for their in vitro protein degradation abilities. Suillus species preferentially occurring in mature forests, where soil contains more organic matter, had significantly higher protease activity than those from young forests with low-organic-matter soils or species indifferent to forest age. Within species, the protease activities of ecotypes from soils with high or low soil organic N content did not differ significantly, suggesting resource partitioning between mineral and organic soil layers. The secreted protease mixtures were strongly dominated by aspartic peptidases. Glucose addition had variable effects on secreted protease activity; in some species, it triggered activity, but in others, activity was repressed at high concentrations. Collectively, our results indicate that protease activity, a key ectomycorrhizal functional trait, is positively related to environmental N source availability but is also influenced by additional factors, such as carbon availability. PMID- 26682856 TI - pyrF as a Counterselectable Marker for Unmarked Genetic Manipulations in Treponema denticola. AB - The pathophysiology of Treponema denticola, an oral pathogen associated with both periodontal and endodontic infections, is poorly understood due to its fastidious growth and recalcitrance to genetic manipulations. Counterselectable markers are instrumental in constructing clean and unmarked mutations in bacteria. Here, we demonstrate that pyrF, a gene encoding orotidine-5'-monophosphate decarboxylase, can be used as a counterselectable marker in T. denticola to construct marker free mutants. T. denticola is susceptible to 5-fluoroorotic acid (5-FOA). To establish a pyrF-based counterselectable knockout system in T. denticola, the pyrF gene was deleted. The deletion conferred resistance to 5-FOA in T. denticola. Next, a single-crossover mutant was constructed by reintroducing pyrF along with a gentamicin resistance gene (aacC1) back into the chromosome of the pyrF mutant at the locus of choice. In this study, we chose flgE, a flagellar hook gene that is located within a large polycistronic motility gene operon, as our target gene. The obtained single-crossover mutant (named FlgE(in)) regained the susceptibility to 5-FOA. Finally, FlgE(in) was plated on solid agar containing 5-FOA. Numerous colonies of the 5-FOA-resistant mutant (named FlgE(out)) were obtained and characterized by PCR and Southern blotting analyses. The results showed that the flgE gene was deleted and FlgE(out) was free of selection markers (i.e., pyrF and aacC1). Compared to previously constructed flgE mutants that contain an antibiotic selection marker, the deletion of flgE in FlgE(out) has no polar effect on its downstream gene expression. The system developed here will provide us with a new tool for investigating the genetics and pathogenicity of T. denticola. PMID- 26682857 TI - Respiratory Kinetics of Marine Bacteria Exposed to Decreasing Oxygen Concentrations. AB - During aerobic respiration, microorganisms consume oxygen (O2) through the use of different types of terminal oxidases which have a wide range of affinities for O2. The Km values for O2 of these enzymes have been determined to be in the range of 3 to 200 nmol liter(-1). In this study, we examined the time course of development of aerobic respiratory kinetics of four marine bacterial species (Dinoroseobacter shibae, Roseobacter denitrificans, Idiomarina loihiensis, and Marinobacter daepoensis) during exposure to decreasing O2 concentrations. The genomes of all four species have genes for both high-affinity and low-affinity terminal oxidases. The respiration rate of the bacteria was measured by the use of extremely sensitive optical trace O2 sensors (range, 1 to 1,000 nmol liter( 1)). Three of the four isolates exhibited apparent Km values of 30 to 60 nmol liter(-1) when exposed to submicromolar O2 concentrations, but a decrease to values below 10 nmol liter(-1) was observed when the respiration rate per cell was lowered and the cell size was decreased due to starvation. The fourth isolate did not reach a low respiration rate per cell during starvation and exhibited apparent Km values of about 20 nmol liter(-1) throughout the experiment. The results clearly demonstrate not only that enzyme kinetics may limit O2 uptake but also that even individual cells may be diffusion limited and that this diffusion limitation is the most pronounced at high respiration rates. A decrease in cell size by starvation, due to limiting organic carbon, and thereby more efficient diffusion uptake may also contribute to lower apparent Km values. PMID- 26682858 TI - Levan-Producing Leuconostoc citreum Strain BD1707 and Its Growth in Tomato Juice Supplemented with Sucrose. AB - A levan-producing strain, BD1707, was isolated from Tibetan kefir and identified as Leuconostoc citreum. The effects of carbon sources on the growth of L. citreum BD1707 and levan production in tomato juice were measured. The changes in pH, viable cell count, sugar content, and levan yield in the cultured tomato juice supplemented with 15% (wt/vol) sucrose were also assayed. L. citreum BD1707 could synthesize more than 28 g/liter of levan in the tomato juice-sucrose medium when cultured at 30 degrees C for 96 h. Based on the monosaccharide composition, molecular mass distribution, Fourier transform infrared (FTIR) spectra, and nuclear magnetic resonance (NMR) spectra, the levan synthesized by L. citreum BD1707 was composed of a linear backbone consisting of consecutive beta-(2->6) linked d-fructofuranosyl units, with an estimated average molecular mass of 4.3 * 10(6) Da. PMID- 26682859 TI - Comparison of Four Comamonas Catabolic Plasmids Reveals the Evolution of pBHB To Catabolize Haloaromatics. AB - Comamonas plasmids play important roles in shaping the phenotypes of their hosts and the adaptation of these hosts to changing environments, and understanding the evolutionary strategy of these plasmids is thus of great concern. In this study, the sequence of the 119-kb 3,5-dibromo-4-hydroxybenzonitrile-catabolizing plasmid pBHB from Comamonas sp. strain 7D-2 was studied and compared with those of three other Comamonas haloaromatic catabolic plasmids. Incompatibility group determination based on a phylogenetic analysis of 24 backbone gene proteins, as well as TrfA, revealed that these four plasmids all belong to the IncP-1beta subgroup. Comparison of the four plasmids revealed a conserved backbone region and diverse genetic-load regions. The four plasmids share a core genome consisting of 40 genes (>50% similarities) and contain 12 to 50 unique genes each, most of which are xenobiotic-catabolic genes. Two functional reductive dehalogenase gene clusters are specifically located on pBHB, showing distinctive evolution of pBHB for haloaromatics. The higher catabolic ability of the bhbA2B2 cluster than the bhbAB cluster may be due to the transcription levels and the character of the dehalogenase gene itself rather than that of its extracytoplasmic binding receptor gene. The plasmid pBHB is riddled with transposons and insertion sequence (IS) elements, and ISs play important roles in the evolution of pBHB. The analysis of the origin of the bhb genes on pBHB suggested that these accessory genes evolved independently. Our work provides insights into the evolutionary strategies of Comamonas plasmids, especially into the adaptation mechanism employed by pBHB for haloaromatics. PMID- 26682860 TI - Chloroflexi CL500-11 Populations That Predominate Deep-Lake Hypolimnion Bacterioplankton Rely on Nitrogen-Rich Dissolved Organic Matter Metabolism and C1 Compound Oxidation. AB - The Chloroflexi CL500-11 clade contributes a large proportion of the bacterial biomass in the oxygenated hypolimnia of deep lakes worldwide, including the world's largest freshwater system, the Laurentian Great Lakes. Traits that allow CL500-11 to thrive and its biogeochemical role in these environments are currently unknown. Here, we found that a CL500-11 population was present mostly in offshore waters along a transect in ultraoligotrophic Lake Michigan (a Laurentian Great Lake). It occurred throughout the water column in spring and only in the hypolimnion during summer stratification, contributing up to 18.1% of all cells. Genome reconstruction from metagenomic data suggested an aerobic, motile, heterotrophic lifestyle, with additional energy being gained through carboxidovory and methylovory. Comparisons to other available streamlined freshwater genomes revealed that the CL500-11 genome contained a disproportionate number of cell wall/capsule biosynthesis genes and the most diverse spectrum of genes involved in the uptake of dissolved organic matter (DOM) substrates, particularly peptides. In situ expression patterns indicated the importance of DOM uptake and protein/peptide turnover, as well as type I and type II carbon monoxide dehydrogenase and flagellar motility. Its location in the water column influenced its gene expression patterns the most. We observed increased bacteriorhodopsin gene expression and a response to oxidative stress in surface waters compared to its response in deep waters. While CL500-11 carries multiple adaptations to an oligotrophic lifestyle, its investment in motility, its large cell size, and its distribution in both oligotrophic and mesotrophic lakes indicate its ability to thrive under conditions where resources are more plentiful. Our data indicate that CL500-11 plays an important role in nitrogen rich DOM mineralization in the extensive deep-lake hypolimnion habitat. PMID- 26682861 TI - Coexistence of Microaerophilic, Nitrate-Reducing, and Phototrophic Fe(II) Oxidizers and Fe(III) Reducers in Coastal Marine Sediment. AB - Iron is abundant in sediments, where it can be biogeochemically cycled between its divalent and trivalent redox states. The neutrophilic microbiological Fe cycle involves Fe(III)-reducing and three different physiological groups of Fe(II)-oxidizing microorganisms, i.e., microaerophilic, anoxygenic phototrophic, and nitrate-reducing Fe(II) oxidizers. However, it is unknown whether all three groups coexist in one habitat and how they are spatially distributed in relation to gradients of O2, light, nitrate, and Fe(II). We examined two coastal marine sediments in Aarhus Bay, Denmark, by cultivation and most probable number (MPN) studies for Fe(II) oxidizers and Fe(III) reducers and by quantitative-PCR (qPCR) assays for microaerophilic Fe(II) oxidizers. Our results demonstrate the coexistence of all three metabolic types of Fe(II) oxidizers and Fe(III) reducers. In qPCR, microaerophilic Fe(II) oxidizers (Zetaproteobacteria) were present with up to 3.2 * 10(6) cells g dry sediment(-1). In MPNs, nitrate reducing Fe(II) oxidizers, anoxygenic phototrophic Fe(II) oxidizers, and Fe(III) reducers reached cell numbers of up to 3.5 * 10(4), 3.1 * 10(2), and 4.4 * 10(4) g dry sediment(-1), respectively. O2 and light penetrated only a few millimeters, but the depth distribution of the different iron metabolizers did not correlate with the profile of O2, Fe(II), or light. Instead, abundances were homogeneous within the upper 3 cm of the sediment, probably due to wave-induced sediment reworking and bioturbation. In microaerophilic Fe(II)-oxidizing enrichment cultures, strains belonging to the Zetaproteobacteria were identified. Photoferrotrophic enrichments contained strains related to Chlorobium and Rhodobacter; the nitrate-reducing Fe(II) enrichments contained strains related to Hoeflea and Denitromonas. This study shows the coexistence of all three types of Fe(II) oxidizers in two near-shore marine environments and the potential for competition and interrelationships between them. PMID- 26682862 TI - Contribution of the Salmonella enterica KdgR Regulon to Persistence of the Pathogen in Vegetable Soft Rots. AB - During their colonization of plants, human enteric pathogens, such as Salmonella enterica, are known to benefit from interactions with phytopathogens. At least in part, benefits derived by Salmonella from the association with a soft rot caused by Pectobacterium carotovorum were shown to be dependent on Salmonella KdgR, a regulator of genes involved in the uptake and utilization of carbon sources derived from the degradation of plant polymers. A Salmonella kdgR mutant was more fit in soft rots but not in the lesions caused by Xanthomonas spp. and Pseudomonas spp. Bioinformatic, phenotypic, and gene expression analyses demonstrated that the KdgR regulon included genes involved in uptake and metabolism of molecules resulting from pectin degradation as well as those central to the utilization of a number of other carbon sources. Mutant analyses indicated that the Entner-Doudoroff pathway, in part controlled by KdgR, was critical for the persistence within soft rots and likely was responsible for the kdgR phenotype. PMID- 26682863 TI - Validation of the Erlangen Score Algorithm for the Prediction of the Development of Dementia due to Alzheimer's Disease in Pre-Dementia Subjects. PMID- 26682865 TI - 'Compliance' versus 'adherence' in sport injury prevention: why definition matters. PMID- 26682866 TI - Neural representations and the cortical body matrix: implications for sports medicine and future directions. AB - Neural representations, or neurotags, refer to the idea that networks of brain cells, distributed across multiple brain areas, work in synergy to produce outputs. The brain can be considered then, a complex array of neurotags, each influencing and being influenced by each other. The output of some neurotags act on other systems, for example, movement, or on consciousness, for example, pain. This concept of neurotags has sparked a new body of research into pain and rehabilitation. We draw on this research and the concept of a cortical body matrix-a network of representations that subserves the regulation and protection of the body and the space around it-to suggest important implications for rehabilitation of sports injury and for sports performance. Protective behaviours associated with pain have been reinterpreted in light of these conceptual models. With a particular focus on rehabilitation of the injured athlete, this review presents the theoretical underpinnings of the cortical body matrix and its application within the sporting context. Therapeutic approaches based on these ideas are discussed and the efficacy of the most tested approaches is addressed. By integrating current thought in pain and cognitive neuroscience related to sports rehabilitation, recommendations for clinical practice and future research are suggested. PMID- 26682868 TI - Weight of evidence evaluation and systematic review in EU chemical risk assessment: Foundation is laid but guidance is needed. AB - The aim of this review was to investigate if and how the application of weight of evidence (WoE) evaluation or systematic review (SR) in chemical risk assessment is promoted within different regulatory frameworks in the European Union. Legislative and relevant guidance documents within nine regulatory frameworks were scrutinized and compared. WoE evaluation or SR is promoted in seven of the investigated frameworks but sufficient guidance for how to perform these processes is generally lacking. None of the investigated frameworks give enough guidance for generating robust and reproducible WoE evaluations or SRs. In conclusion, the foundation for use of WoE evaluation and SR is laid in the majority of the investigated frameworks, but there is a need to provide more structured and detailed guidance. In order to make the process of developing guidance as efficient as possible, and to ensure smooth transfer of risk assessment's between frameworks if a chemical is risk assessed both as, for example, a biocide and an industrial chemical, it is recommended that guidance is developed jointly by the European regulatory agencies. PMID- 26682867 TI - The impact of short periods of match congestion on injury risk and patterns in an elite football club. AB - BACKGROUND: The effect of fixture congestion on injury rates and patterns has received scarce attention in elite football and existing investigations have not accounted for player rotation or examined the temporal distribution and potential cause of injuries. AIM: To prospectively investigate the epidemiology of injury during short periods of fixture congestion in a professional football club. METHODS: Over a six-season period, exposure time and injury data were compared in the same players (n=25 (14 individuals)) when participating in two frequently occurring short congested fixture cycles in comparison to match-play outside these cycles. (1) two successive matches separated by an interval totalling <=3 days calculated immediately from the end of play in match 1 to the beginning of play in match 2; (2) three successive matches separated by <=4-day intervals starting the day immediately after each match. RESULTS: In two-match congestion cycles, incidence rate ratios (IRR) showed that there was a higher risk of injury in the final 15 min of play in the second match in comparison to match-play outside the cycles (IRR: 3.1 (95% CI 1.1 to 9.3), p=0.0400). A greater risk of injury overall (IRR: 2.0 (95% CI 1.1 to 3.8), p=0.0345) and in the first-half of play (2.6 (1.1 to 6,5), p=0.0386), and risk of ankle sprains (10.4 (95% CI 1.9 to 57.9), p=0.0068) and non-contact injuries due to a 'change in direction' (IRR: 7.8 (1.3 to 46.8), p=0.0243) were observed in the final match of three-match congestion cycles in comparison to match-play outside the cycles. CONCLUSIONS: Injury rates and patterns were affected in the same elite football players when competing in short congested fixture cycles in comparison to match-play outside the cycles. PMID- 26682869 TI - Death certificate only proportions should be age adjusted in studies comparing cancer survival across populations and over time. AB - BACKGROUND: The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. METHODS: Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. RESULTS: Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65 74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. CONCLUSIONS: The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time. PMID- 26682870 TI - Targeting the Janus-activated kinase-2-STAT3 signalling pathway in pancreatic cancer using the HSP90 inhibitor ganetespib. AB - BACKGROUND: Pancreatic cancer (PC) is an aggressive malignancy characterised by chemoresistance. HSP90 is important for stabilisation of proteins, cell signalling and malignant growth. We hypothesised that ganetespib, an HSP90 inhibitor, can inhibit PC cell growth by interfering with multiple signalling cascades, including the Janus-activated kinase (JAK)-STAT pathway, and act synergistically with chemotherapeutic drugs. METHODS: The effects of ganetespib were evaluated in ASPC-1, HPAC, MIA PaCA-2 and PANC-1 cell lines using a cell proliferation assay. Effects on the expression of phosphoinositide 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK) and JAK-STAT pathways were examined by Western blot. JAK2 and STAT3 were knocked down by transient transfection with JAK2 or STAT3 small interfering RNA. ASPC-1 and HPAC cell lines were tested for sensitivity to ganetespib, 5-fluorouracil/oxaliplatin, and gemcitabine/paclitaxel, alone and in combination, using an in vivo tumour xenograft model. RESULTS: Ganetespib significantly decreased cell proliferation in all tested PC cell lines. Ganetespib decreased the activation of extracellular signal-related kinase (ERK), PI3K/AKT, and c-Jun NH2-terminal kinase (JNK) signalling molecules and diminished the activation of STAT3 in an additive manner with isolated downregulation of JAK2 expression. In animal models, ganetespib potentiated the effects of 5-fluouracil/oxaliplatin and gemcitabine/paclitaxel, as measured by tumour volume. Western blot analysis from tumours removed from animals confirmed the effects of ganetespib on PI3K/AKT, ERK and JNK pathways. CONCLUSIONS: Ganetespib inhibits the growth of PC cells, an effect associated with downregulation of signalling through the JAK2-STAT3, PI3K/AKT and MAPK pathways. This provides preclinical proof-of-principle that ganetespib enhances the activity of chemotherapeutic agents and warrants further evaluation in PC clinical trials. PMID- 26682871 TI - Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients. AB - BACKGROUND: We investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We included 451 NSCLC patients aged 70-89 years enrolled in the Intergroupe Francophone de Cancerologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS. RESULTS: Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980-0.992). We distinguished three groups according to GH score: high (GH <46), intermediate (46 <= GH <= 67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001). In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49-1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54-0.96; P=0.023 and HR: 0.50; 95% CI: 0.30-0.84; P=0.0089, respectively). CONCLUSION: This study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy. PMID- 26682872 TI - Post-traumatic hypopituitarism and fatigue. AB - Post-traumatic hypopituitarism (PTH) associated with chronic cognitive, psychiatric, and/or behavioural sequelae is common following moderate to severe traumatic brain injury (TBI). More specifically, due to a cascade of hormonal deficiencies secondary to PTH, individuals with TBI may experience debilitating fatigue that can negatively impact functional recovery, as it can limit participation in brain injury rehabilitation services and lead to an increase in maladaptive lifestyle practices. While the mechanisms underlying fatigue and TBI are not entirely understood, the current review will address the specific anatomy and physiology of the pituitary gland, as well as the association between pituitary dysfunction and fatigue in individuals with TBI. PMID- 26682873 TI - Evolution of Irradiation-Induced Vacancy Defects in Boron Nitride Nanotubes. AB - Irradiation-induced vacancy defects in multiwalled (MW) boron nitride nanotubes (BNNTs) are investigated via in situ high-resolution transmission electron microscope operated at 80 kV, with a homogeneous distribution of electron beam intensity. During the irradiation triangle-shaped vacancy defects are gradually generated in MW BNNTs under a mediate electron current density (30 A cm(-2)), by knocking the B atoms out. The vacancy defects grow along a well-defined direction within a wall at the early stage as a result of the curvature induced lattice strain, and then develop wall by wall. The orientation or the growth direction of the vacancy defects can be used to identify the chirality of an individual wall. With increasing electron current density, the shape of the irradiation-induced vacancy defects changes from regular triangle to irregular polygon. PMID- 26682874 TI - Bronchoscopy, Imaging, and Concurrent Diseases in Dogs with Bronchiectasis: (2003 2014). AB - BACKGROUND: Bronchiectasis is a permanent and debilitating sequel to chronic or severe airway injury, however, diseases associated with this condition are poorly defined. OBJECTIVE: To evaluate results of diagnostic tests used to document bronchiectasis and to characterize underlying or concurrent disease processes. ANIMALS: Eighty-six dogs that had bronchoscopy performed and a diagnosis of bronchiectasis. METHODS: Retrospective case series. Radiographs, computed tomography, and bronchoscopic findings were evaluated for features of bronchiectasis. Clinical diagnoses of pneumonia (aspiration, interstitial, foreign body, other), eosinophilic bronchopneumopathy (EBP), and inflammatory airway disease (IAD) were made based on results of history, physical examination, and diagnostic testing, including bronchoalveolar lavage fluid analysis and microbiology. RESULTS: Bronchiectasis was diagnosed in 14% of dogs (86/621) that had bronchoscopy performed. Dogs ranged in age from 0.5 to 14 years with duration of signs from 3 days to 10 years. Bronchiectasis was documented during bronchoscopy in 79/86 dogs (92%), thoracic radiology in 50/83 dogs (60%), and CT in 34/34 dogs (100%). Concurrent airway collapse was detected during bronchoscopy in 50/86 dogs (58%), and focal or multifocal mucus plugging of segmental or subsegmental bronchi was found in 41/86 dogs (48%). Final diagnoses included pneumonia (45/86 dogs, 52%), EBP (10/86 dogs, 12%) and IAD (31/86 dogs, 36%). Bacteria were isolated in 24/86 cases (28%), with Streptococcus spp, Pasteurella spp, enteric organisms, and Stenotrophomonas isolated most frequently. CONCLUSIONS AND CLINICAL IMPORTANCE: Bronchiectasis can be anticipated in dogs with infectious or inflammatory respiratory disease. Advanced imaging and bronchoscopy are useful in making the diagnosis and identifying concurrent respiratory disease. PMID- 26682875 TI - Patient experiences of perioperative nutrition within an Enhanced Recovery After Surgery programme for colorectal surgery: a qualitative study. AB - AIM: Nutrition is an important element of the Enhanced Recovery After Surgery (ERAS) programme. Patients have previously indicated that nutrition is a key component of ERAS that requires improvement. Our aim was to explore the perioperative nutrition experiences of colorectal surgical patients to identify barriers and facilitators to the integration of nutrition within ERAS. METHOD: Sixteen individuals undergoing colorectal surgery participated in a semi structured interview between postoperative day three and hospital discharge. The topic guide was developed iteratively throughout the study; topics included preoperative counselling, carbohydrate loading, fasting and postoperative nutrition. A constant comparison technique was employed during coding, and an inductive thematic analysis was used. Validity was ensured by double coding a sample of transcripts. RESULTS: Findings are presented in the context of the following clinical themes: preoperative information, preoperative fasting, carbohydrate loading and nutritional drinks, postoperative diet and discharge. Individuals received too much general information which was repetitive, contradictory and not disease specific; this formed a key barrier affecting nutrition. Other barriers were negative experiences of nutritional drinks, stoma management, nausea and vomiting, and challenges from the hospital environment. Facilitators included interactions with staff, food accessibility and choice, and motivation for discharge. CONCLUSION: The key barrier to adherence of perioperative nutrition protocols was poor provision of information. Targeted information regarding postoperative diet, stoma management and coping with nausea and vomiting would be beneficial for colorectal surgical patients. Easily accessible food provided by ward staff was considered a facilitator. PMID- 26682876 TI - Comparative analysis of the tubulin cytoskeleton organization in nodules of Medicago truncatula and Pisum sativum: bacterial release and bacteroid positioning correlate with characteristic microtubule rearrangements. AB - In this study we analyzed and compared the organization of the tubulin cytoskeleton in nodules of Medicago truncatula and Pisum sativum. We combined antibody labeling and green fluorescent protein tagging with laser confocal microscopy to observe microtubules (MTs) in nodules of both wild-type (WT) plants and symbiotic plant mutants blocked at different steps of nodule development. The 3D MT organization of each histological nodule zone in both M. truncatula and P. sativum is correlated to specific developmental processes. Endoplasmic MTs appear to support infection thread growth, infection droplet formation and bacterial release into the host cytoplasm in nodules of both species. No differences in the organization of the MT cytoskeleton between WT and bacterial release mutants were apparent, suggesting both that the phenotype is not linked to a defect in MT organization and that the growth of hypertrophied infection threads is supported by MTs. Strikingly, bacterial release coincides with a change in the organization of cortical MTs from parallel arrays into an irregular, crisscross arrangement. After release, the organization of endoplasmic MTs is linked to the distribution of symbiosomes. The 3D MT organization of each nodule histological zone in M. truncatula and P. sativum was analyzed and linked to specific developmental processes. PMID- 26682877 TI - Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts. AB - AIM OF THE STUDY: Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. MATERIALS AND METHODS: Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 MUL phosphate buffered saline and the ALLO/SVF group received 100 MUL SVF (2.25 +/- 0.45 * 10(7) cells) locally where the grafting was performed. RESULTS: Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). CONCLUSIONS: Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection. PMID- 26682887 TI - A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis. AB - Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA) formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat.) D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST) that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium. PMID- 26682888 TI - Vertebral Pneumaticity in the Ornithomimosaur Archaeornithomimus (Dinosauria: Theropoda) Revealed by Computed Tomography Imaging and Reappraisal of Axial Pneumaticity in Ornithomimosauria. AB - Among extant vertebrates, pneumatization of postcranial bones is unique to birds, with few known exceptions in other groups. Through reduction in bone mass, this feature is thought to benefit flight capacity in modern birds, but its prevalence in non-avian dinosaurs of variable sizes has generated competing hypotheses on the initial adaptive significance of postcranial pneumaticity. To better understand the evolutionary history of postcranial pneumaticity, studies have surveyed its distribution among non-avian dinosaurs. Nevertheless, the degree of pneumaticity in the basal coelurosaurian group Ornithomimosauria remains poorly known, despite their potential to greatly enhance our understanding of the early evolution of pneumatic bones along the lineage leading to birds. Historically, the identification of postcranial pneumaticity in non-avian dinosaurs has been based on examination of external morphology, and few studies thus far have focused on the internal architecture of pneumatic structures inside the bones. Here, we describe the vertebral pneumaticity of the ornithomimosaur Archaeornithomimus with the aid of X-ray computed tomography (CT) imaging. Complementary examination of external and internal osteology reveals (1) highly pneumatized cervical vertebrae with an elaborate configuration of interconnected chambers within the neural arch and the centrum; (2) anterior dorsal vertebrae with pneumatic chambers inside the neural arch; (3) apneumatic sacral vertebrae; and (4) a subset of proximal caudal vertebrae with limited pneumatic invasion into the neural arch. Comparisons with other theropod dinosaurs suggest that ornithomimosaurs primitively exhibited a plesiomorphic theropod condition for axial pneumaticity that was extended among later taxa, such as Archaeornithomimus and large bodied Deinocheirus. This finding corroborates the notion that evolutionary increases in vertebral pneumaticity occurred in parallel among independent lineages of bird-line archosaurs. Beyond providing a comprehensive view of vertebral pneumaticity in a non-avian coelurosaur, this study demonstrates the utility and need of CT imaging for further clarifying the early evolutionary history of postcranial pneumaticity. PMID- 26682889 TI - Impacts of Climate Change on the Timing of the Production Season of Maple Syrup in Eastern Canada. AB - Maple syrup production is an important economic activity in north-eastern North America. The beginning and length of the production season is linked to daily variation in temperature. There are increasing concerns about the potential impact of climatic change on this industry. Here, we used weekly data of syrup yield for the 1999-2011 period from 121 maple stands in 11 regions of Quebec (Canada) to predict how the period of production may be impacted by climate warming. The date at which the production begins is highly variable between years with an average range of 36 days among the regions. However, the average start date for a given region, which ranged from Julian day 65 to 83, was highly predictable (r2 = 0.88) using the average temperature from January to April (TJ A). A logistic model predicting the weekly presence or absence of production was also developed. Using the inputs of 77 future climate scenarios issued from global models, projections of future production timing were made based on average TJ-A and on the logistic model. The projections of both approaches were in very good agreement and suggest that the sap season will be displaced to occur 15-19 days earlier on average in the 2080-2100 period. The data also show that the displacement in time will not be accompanied by a greater between years variability in the beginning of the season. However, in the southern part of Quebec, very short periods of syrup production due to unfavourable conditions in the spring will occur more frequently in the future although their absolute frequencies will remain low. PMID- 26682890 TI - Radioxenon standards used in laboratory inter-comparisons. AB - Preparation methods for (133)Xe standards of activity concentration and the results of the 2014 (133)Xe laboratory inter-comparison exercise are described. One element of the quality assurance/quality control (QA/QC) program for laboratories of the International Monitoring System (IMS) will be regular inter comparison exercises. However, until recently, no activity concentration standards for benchmarking were available. Therefore, two (133)Xe activity concentration reference standards were produced independently by Idaho National Laboratory and Seibersdorf Laboratories and used for the 2014 laboratory inter comparison exercise. The preparation of a complementary (127)Xe activity concentration standard as well as a (127)Xe laboratory inter-comparison exercise suggests (127)Xe as a suitable isotope for QA/QC of remote IMS noble gas stations. PMID- 26682891 TI - Tracing radioactivity from Fukushima in the Northern Pacific Ocean. AB - Following the accident at the Fukushima Daiichi nuclear power plant, a campaign of sampling and measuring anthropogenic radionuclides in North Pacific seawater was set up. The main aim was to study natural processes using these radionuclides as tracers. Because of dilution, the activities of anthropogenic radionuclides at long range were very low and their measurement required advanced pre concentration techniques and underground gamma-ray spectrometry. Data and metrological aspects of the measurements using HPGe-detectors are presented and discussed. PMID- 26682892 TI - Low level measurement of (60)Co by gamma ray spectrometry using gamma-gamma coincidence. AB - This paper presents the latest development of the laboratory to measure the natural and artificial massic activities in environmental samples. The measurement method of coincident emitters by gamma-gamma coincidence using an anti-Compton device and its digital electronics is described. Results obtained with environmental samples are shown. Despite its low efficiency, this method decreases detection limits of (60)Co for certain samples compared to conventional gamma-ray spectrometry due to its very low background. PMID- 26682893 TI - Corrections for the combined effects of decay and dead time in live-timed counting of short-lived radionuclides. AB - Studies and calibrations of short-lived radionuclides, for example (15)O, are of particular interest in nuclear medicine. Yet counting experiments on such species are vulnerable to an error due to the combined effect of decay and dead time. Separate decay corrections and dead-time corrections do not account for this issue. Usually counting data are decay-corrected to the start time of the count period, or else instead of correcting the count rate, the mid-time of the measurement is used as the reference time. Correction factors are derived for both those methods, considering both extending and non-extending dead time. Series approximations are derived here and the accuracy of those approximations are discussed. PMID- 26682894 TI - Comparison of (18)F activity measurements at the VNIIM, NPL and the ENEA-INMRI using the SIRTI of the BIPM. AB - In 2014, the first three comparisons of activity measurements of (18)F were carried out at the VNIIM, NPL and the ENEA-INMRI using the BIPM's Transfer Instrument of the International Reference System. The transfer instrument and the NMIs primary measurement methods are briefly described. The degrees of equivalence with the key comparison reference value defined in the frame of the corresponding SIR comparison have been evaluated. World-wide consistency of activity measurements of (18)F is demonstrated. PMID- 26682895 TI - Defined solid angle alpha counting at NPL. AB - This paper describes the design of and first measurements with the new defined solid angle (DSA) alpha counter at the National Physical Laboratory, UK, with the aim of enabling high-precision radionuclide standardisations for alpha-emitting radionuclides and half-life measurements. The counter may be employed at three source-detector distances in order to monitor the measured activities with calculated geometrical efficiencies. Initial results are promising but further work is required to reduce the dominant uncertainty associated with the source activity distribution. PMID- 26682896 TI - Development of a calibration system for airborne (131)I monitoring devices. AB - A prototype calibration system for airborne (131)I monitoring devices was developed at the Shanghai Institute of Measurement and Testing Technology (SIMT). This system consists of a gaseous (131)I2 generator, an airborne storage chamber, an airborne iodine sampler, and an HPGe spectrometer. With this system, (131)I reference samples in the form of charcoal filters and charcoal cartridges, with activities ranging from 100 to 10,000Bq, were produced with overall relative standard uncertainties of 2.8% (for filter samples) and 3.5% (for cartridge samples); the activities range could be extended according to need. PMID- 26682897 TI - Reintroduction of the European Capercaillie from the Capercaillie Breeding Centre in Wisla Forest District: Genetic Assessments of Captive and Reintroduced Populations. AB - The Western capercaillie (Tetrao urogallus) is a specific bird species, which, despite its very broad distribution and large global population size, is highly endangered in many Western and Central European countries. According to the species situation, in many countries (including Poland), breeding and reintroduction programmes have been started. One of the most complex and large scale reintroduction programmes was started in Bory Dolnoslaskie Forest, and the Capercaillie Breeding Centre in Wisla Forest District was used as one of the sources of individuals for reintroduction. As genetic tools provide essential knowledge about species biodiversity, which is crucially important during the breeding process and reintroduction, both captive and reintroduced grouse populations were genetically analysed. We were particularly interested in genetic diversity of the individuals in both populations and the genetic relationship between them, as well as between them and other capercaillie representatives from their current range. To fulfil these goals we determined nine microsatellite loci along with a fragment of the mitochondrial control region. Genetic diversity parameters were moderate to high compared to populations from other Central and Western European countries. Both populations were clustered into three distinct genetic clades based on microsatellites. Phylogenetic analysis placed all mitochondrial haplotypes we revealed in the Eurasian clade. The present results will play an important role as they will help to preserve and maximize genetic diversity in captive populations, and will provide a basis for future monitoring of the reintroduction process. PMID- 26682898 TI - (RS)-Propranolol: enantioseparation by HPLC using newly synthesized (S) levofloxacin-based reagent, absolute configuration of diastereomers and recovery of native enantiomers by detagging. AB - Diastereomers of (RS)-propranolol were synthesized using (S)-levofloxacin-based new chiral derivatizing reagents (CDRs). Levofloxacin was chosen as the pure (S) enantiomer for its high molar absorptivity (epsilono ~ 24000) and availability at a low price. Its -COOH group had N-hydroxysuccinimide and N hydroxybenzotriazole, which acted as good leaving groups during nucleophilic substitution by the amino group of the racemic (RS)-propranolol; the CDRs were characterized by UV, IR, (1) H-NMR, high resolution mass spectrometry (HRMS) and carbon, hydrogen, nitrogen, and sulphur fundamental elemental components analyser (CHNS). Diastereomers were separated quantitatively using open column chromatography; absolute configuration of the diastereomers was established and the reagent moiety was detagged under microwave-assisted acidic conditions. (S)- and (R)-propranolol as pure enantiomers and (S)-levofloxacin were separated, isolated and characterized. Optimized lowest-energy structures of the diastereomers were developed using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set (based on density functional theory) for explanation of elution order and configuration. In addition, RP HPLC conditions for separation of diastereomers were optimized with respect to pH, concentration of buffer, flow rate of mobile phase and nature of organic modifier. HPLC separation method was validated as per International Conference on Harmonization guidelines. With the systematic application of various analytical techniques, absolute configuration of the diastereomers (and the native enantiomers) of (RS)-propranolol was established. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26682899 TI - How Growing Complexity of Consumer Choices and Drivers of Consumption Behaviour Affect Demand for Animal Source Foods. AB - Many societies are spoiled for choice when they purchase meat and other livestock products, and around the globe food choice has grown dramatically in the last two decades. What is more, besides the cost and obvious health concerns influencing commodity section, an increasing proportion of choices is made to contribute to the achievement of certain ideals, such as natural resource management, climate change mitigation, animal welfare concerns and personal lifestyle. At the same time, human health considerations are becoming more important for consumption choices as richer societies, and increasingly the urban poor in low- and middle income countries, face an unprecedented epidemic of over-consumption and associated diet-related non-communicable diseases. Animal source foods are considered significant contributors to this trend. This paper reviews this complicated arena, and explores the range of considerations that influence consumers' preferences for meat and other animal source foods. This paper also argues that deeper drivers of consumption behaviour of many foods may act in opposition to the articulated preferences for choices around animal source food consumption. We review how the returns to different causes are being valued, how emerging metrics are helping to manage and influence consumption behaviours, and draw conclusions regarding options which influence food choice. PMID- 26682900 TI - Erratum to: Role of central and peripheral opioid receptors in the cardioprotection of intravenous morphine preconditioning. PMID- 26682901 TI - Total-tau and neurofilament light in CSF reflect spinal cord ischaemia after endovascular aortic repair. AB - BACKGROUND: Repair of extensive aortic disease may be associated with spinal cord ischaemia (SCI). Here we test if levels of cerebrospinal fluid (CSF) biomarkers for neuronal injury are altered in patients with SCI after advanced endovascular repair in extensive aortic disease. METHODS: CSF was sampled for up to 48 h in ten patients undergoing endovascular aortic repair and analyzed for the axonal damage markers total-tau (T-tau) and neurofilament light (NFL). RESULTS: Six of ten patients developed SCI (clinically present within 3-6 h). CSF levels of NFL increased up to 37-fold in patients with, but were stable in patients without, SCI. CSF levels of T-tau also increased in patients with SCI, but with some overlap with patients without SCI. Levels of NFL and T-tau did not increase until after the appearance of clinical signs of neurological dysfunction (12-48 h after aortic repair). CONCLUSIONS: The CSF biomarkers NFL and T-tau both reflect development of SCI after endovascular aortic repair, but do not rise until after clinical signs of SCI appear. Future studies are desirable to further evaluate potential use of these biomarkers for assessment of the severity of SCI, and also to identify earlier biomarkers of SCI. PMID- 26682902 TI - Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats. AB - Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits. PMID- 26682903 TI - [Technical principles of OCT angiography]. AB - BACKGROUND: Optical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non invasive diagnostic devices for visualization of the retinal and choroidal blood circulation. METHODS: This article is based on a selective literature review and analyses of own data. RESULTS: The advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation. CONCLUSION: Of all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena. PMID- 26682904 TI - [Position statement of the German Ophthalmological Society on early recognition of glaucoma : August 2015]. PMID- 26682905 TI - Impaired Toll-like receptor 2-mediated Th1 and Th17/22 cytokines secretion in human peripheral blood mononuclear cells from patients with atopic dermatitis. AB - BACKGROUND: Impaired Toll-like receptor 2 (TLR2) function has been associated with the pathogenesis of atopic dermatitis (AD). However, there are only few studies reporting on the TLR2-induced immunological responses of circulating leucocytes of AD patients. We thus investigated the expression and secretion of Th1, Th2 and Th17/22 cytokines triggered by TLR2 ligands in human peripheral blood mononuclear cells (PBMCs) from AD patients. Expression of TLR2, 1, 6 and high-affinity receptor for IgE (FcepsilonRI) were further investigated to evaluate the outcome of immune response in AD. METHODS: Expression of TLR2, 1, 6 and FcepsilonRI in PBMCs from AD patients and healthy individuals were measured by qPCR. Subsequent to stimulation with TLR2 ligands PGN and Pam3CSK4, expression and secretion of Th1, Th2 and Th17/22 cytokines were investigated by qPCR and ELISA. RESULTS: The levels of TLR2, 1, 6 mRNA were not altered in both groups of subjects while that of FcepsilonRI was increased in AD patients. Subsequent to the activation by TLR2 ligands, PBMCs from AD patients significantly released less IFN-gamma, IL-17F and IL-22 than those from healthy controls while no detectable level of release was observed with the other cytokines. In contrast, significantly higher levels of mRNA expression for TNF-alpha, IL5, IL-17A and IL 22 were observed in TLR2 activated PBMCs of AD patients than those of healthy control. CONCLUSIONS: PBMCs from AD patients are defective in the secretion of Th1 and Th17/22 cytokines in response to TLR2 ligands. The inconsistent increased expression of the mRNA for the corresponding Th1 cytokines and the Th2 cytokines IL-5 suggested that there may be alterations of downstream signaling events in the cytokine release mechanisms of PBMCs that are associated with the development of AD. PMID- 26682906 TI - Retrospective analysis of the efficacy of chemotherapy and molecular targeted therapy for advanced pulmonary pleomorphic carcinoma. AB - BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) follows an aggressive clinical course and outcomes are disappointing. Due to its rarity, however, the clinicopathological and molecular characteristics of this disease remain unclear. METHODS: We retrospectively evaluated the efficacy of chemotherapy and molecular targeted therapy in 16 patients with PPC who received chemotherapy or EGFR-TKI. We also investigated the status of EGFR mutation, KRAS mutation and ALK expression. RESULTS: On histologic review of the malignant epithelial component, adenocarcinoma was identified in seven cases (43.8%), large cell carcinoma in four (25.0%), and squamous cell carcinoma in two (12.5%). For the sarcomatoid component, 14 cases (87.5%) had both spindle cell tumor and giant cell and 2 (12.5%) had giant cell. Eleven patients received cytotoxic chemotherapy as first line but did not achieve an objective response, although one patient who received docetaxel as second-line achieved a partial response. We also found that one patient achieved long stable disease of about 9 years without progression after receiving cisplatin and gemcitabine treatment. EGFR mutation, KRAS mutation and ALK expression were investigated in 14 patients whose tumor specimens were available. EGFR mutation was observed in 2 (14.3%) and KRAS mutation in 3 (21.4%), while no patient was positive for ALK expression. One patient harboring EGFR exon 19 deletion was treated with gefitinib after postoperative recurrence and achieved a complete response of about 35 months. CONCLUSIONS: Although advanced PPC showed a poor response to chemotherapy, one patient with EGFR mutation achieved an extended complete response. We therefore recommend the evaluation of driver gene alteration such as EGFR in the treatment of advanced PPC. PMID- 26682907 TI - ENDOXY - Development of a Biomimetic Oxygenator-Test-Device. AB - OBJECTIVE: This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term therapy. Tissue engineering uses autologous cell sources to overcome the immunogenic barriers of biomaterials. Surface coating with endothelial cells might improve hemocompatibility and thus prevent immunogenic reactions of the body. In this study this concept is applied to endothelialise a gas-permeable membrane to develop a biomimetic oxygenator test-device (ENDOXY). METHODS: ENDOXY a multifunctional test-system was developed to endothelialise a gas-permeable membrane suitable for cell culture and to test the cell retention under shear stress and to measure gas transfer through it. RESULTS: Successful endothelialisation of the membrane was achieved and cells showed characteristic endothelial morphologies. They stained positive for endothelial markers. The number of cells aligned with shear stress and cell retention after blood perfusing experiments was high. Gas transfer is observed via uncoated and endothelialised membranes. CONCLUSION: The study showed promising results with regard to system design, endothelialisation, and cell retention under shear stress conditions. It strongly encourages further research into the system by testing different membrane materials to design a biomimetic membrane surface and pave way for a fully hemocompatible oxygenator. PMID- 26682909 TI - Tetracarpidium conophorum ameliorates oxidative reproductive toxicity induced by ethanol in male rats. AB - BACKGROUND: Tetracarpidium conophorum (Mull. Arg.) Hutch. & Dalz is one of the many medicinal plants used for ages in folklore as male fertility enhancers. The current study evaluates the effect of the plant leaf extract on alcohol - induced reproductive toxicity in male rats. METHODS: Thirty rats were randomly divided into six groups of five animals each; Group 1 (positive control) received normal saline only; Group 2 (ethanol alone) were given only 30 % ethanol orally at 7 ml/kg body weight per day, thrice in a week; Group 3, 4, 5 were given ethanol and co-treated with 50 mg/kg, 500 mg/kg and 1000 mg/kg body weight of leaf extract respectively while Group 6 were given ethanol and co-treated with a fertility drug, clomiphene citrate. All the drugs were given daily and the experiment lasted for twenty one consecutive days. RESULTS: Alcohol ingestion resulted in a significant (p < 0.05) decrease in water, food intake and marked elevation of lipid peroxidation as assessed by the accumulation of malondialdehyde (MDA) in the reproductive tissues. Precisely, MDA level was elevated in the testis, epididymis, seminal vesicle and prostate gland by 81 %, 63 %, 95 % and 91 %, respectively. Furthermore, levels of total protein, reduced glutathione (GSH), vitamin C and activities of antioxidant enzymes in the reproductive tissues were significantly (p < 0.0001) reduced in ethanol-ingested rats. Interestingly, co administration of T. conophorum with ethanol led to almost complete inhibition of lipid peroxidation thereby enhancing antioxidant status of the reproductive tissues. CONCLUSION: Overall, T. conophorum ameliorates oxidative reproductive toxicity induced by ethanol in male rats and its ameliorative effect comparable well with the fertility drug, clomiphene citrate. PMID- 26682910 TI - Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-kappaB pathways. AB - INTRODUCTION: Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. RESULTS: Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-kappaB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. CONCLUSION: These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs. PMID- 26682911 TI - Cluster adjusted regression for displaced subject data (CARDS): Marginal inference under potentially informative temporal cluster size profiles. AB - Ignorance of the mechanisms responsible for the availability of information presents an unusual problem for analysts. It is often the case that the availability of information is dependent on the outcome. In the analysis of cluster data we say that a condition for informative cluster size (ICS) exists when the inference drawn from analysis of hypothetical balanced data varies from that of inference drawn on observed data. Much work has been done in order to address the analysis of clustered data with informative cluster size; examples include Inverse Probability Weighting (IPW), Cluster Weighted Generalized Estimating Equations (CWGEE), and Doubly Weighted Generalized Estimating Equations (DWGEE). When cluster size changes with time, i.e., the data set possess temporally varying cluster sizes (TVCS), these methods may produce biased inference for the underlying marginal distribution of interest. We propose a new marginalization that may be appropriate for addressing clustered longitudinal data with TVCS. The principal motivation for our present work is to analyze the periodontal data collected by Beck et al. (1997, Journal of Periodontal Research 6, 497-505). Longitudinal periodontal data often exhibits both ICS and TVCS as the number of teeth possessed by participants at the onset of study is not constant and teeth as well as individuals may be displaced throughout the study. PMID- 26682912 TI - The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study. AB - OBJECTIVE: The study aims to investigate the effects of diabetes mellitus (DM) on ovarian injury and reserve in a rat model. STUDY DESIGN: In this prospective experimental study, 16 female Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into 2 groups. Group 1 included 8 normal healthy rats as controls. No drug was administered to the controls. Group 2 included the other 8 rats in which diabetes was induced by intraperitoneal injections of streptozotocin (STZ). After overt DM occurred (blood glucose >250 mg/dl), all the animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Immunoexpressions of nuclear factor-kappa B (NF-kB) and caspase-3 as well as anti-Mullerian hormone (AMH) levels were assessed. Values were analyzed by t test. RESULTS: Immunoexpressions of NF-kB and caspase-3 were significantly higher in non-treated diabetic rats than in the control group (p = 0.011 and p = 0.010, respectively). In healthy control group, AMH levels (3.22 +/- 0.58 ng/ml) were significantly higher than in the non-treated diabetic group (1.41 +/- 0.25 ng/dl; p = 0.024). CONCLUSION: Hyperglycemia causes severe ovarian injury via NF kB pathway and caspase-3 apoptotic pathway, leading to the decrease in ovarian reserve in STZ-induced diabetic rats. PMID- 26682913 TI - Estimation of allele-specific Ace-1 duplication in insecticide-resistant Anopheles mosquitoes from West Africa. AB - BACKGROUND: Identification of variation in Ace-1 copy number and G119S mutation genotype from samples of Anopheles gambiae and Anopheles coluzzii across West Africa are important diagnostics of carbamate and organophosphate resistance at population and individual levels. The most widespread and economical method, PCR RFLP, suffers from an inability to discriminate true heterozygotes from heterozygotes with duplication. METHODS: In addition to PCR-RFLP, in this study three different molecular techniques were applied on the same mosquito specimens: TaqMan qPCR, qRTPCR and ddPCR. To group heterozygous individuals recorded from the PCR-RFLP analysis into different assumptive genotypes K-means clustering was applied on the Z-scores of data obtained from both the TaqMan and ddPCR methods. The qRTPCR analysis was used for absolute quantification of copy number variation. RESULTS: The results indicate that most heterozygotes are duplicated and that G119S mutation must now be regarded as a complex genotype ranging from primarily single-copy susceptible Glycine homozygotes to balanced and imbalanced heterozygotes, and multiply-amplified resistant Serine allele homozygotes. Whilst qRTPCR-based gene copy analysis suffers from some imprecision, it clearly illustrates differences in copy number among genotype groups identified by TaqMan or ddPCR. Based on TaqMan method properties, and by coupling TaqMan and ddPCR methods simultaneously on the same type of mosquito specimens, it demonstrated that the TaqMan genotype assays associated with the K-means clustering algorithm could provide a useful semi-quantitative estimate method to investigate the level of allele-specific duplication in mosquito populations. CONCLUSIONS: Ace-1 gene duplication is evidently far more complex in An. gambiae and An. coluzzii than the better-studied mosquito Culex quinquefasciatus, which consequently can no longer be considered an appropriate model for prediction of phenotypic consequences. These require urgent further evaluation in Anopheles. To maintain the sustained effectiveness carbamates and organophosphates as alternative products to pyrethroids for malaria vector control, monitoring of duplicated resistant alleles in natural populations is essential to guide the rational use of these insecticides. PMID- 26682915 TI - Islet Transplantation in Pediatric Patients: Current Indications and Future Perspectives. AB - The first islet transplantation in diabetes mellitus was performed more than 20 years ago. Since then, clinical results have progressively improved. Nowadays, islet transplantation can be considered a real therapeutic option after pancreatectomy for painful chronic pancreatitis (autotransplantation) and in selected adult patients affected by type 1 diabetes mellitus (allotransplantation). Better results are mainly due to the advances in the standardization of islet isolation and purification procedures as well as in the pharmacological treatment of recipients. Anti-inflammatory treatments facilitate islet engraftment and prevent metabolic exhaustion and functional beta-cell apoptosis; new strategies better control islet graft rejection. As a consequence, islet transplantation activities are no longer confined to few centers only, rather thousands of transplants are now performed all over the world. Many attempts are actually undertaken to find solutions to current problems of islets transplantation, from toxicity of immunosuppressive therapy to the limited engraftment, function and duration. There is general hope that these procedures will offer a safe and feasible therapeutic option for an increasing number of patients suffering from diabetes mellitus, including pediatric patients. PMID- 26682914 TI - Comparative Study on the Roles of the Number of Accelerations and Rotation Angle in the Treatment Maneuvers for Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo. AB - AIMS: This study aims to investigate the roles of the number of accelerations and rotation angle in the treatment of posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV). METHODS: We enrolled 344 patients with unilateral PC-BPPV. Of these, 167 patients in the simple-step maneuver (SSM) group were accelerated twice and rotated 120 degrees per step, whereas 177 patients in the multi-step maneuver (MSM) group were accelerated 4 times and rotated 60 degrees per step. Dix-Hallpike (DH) tests were performed to categorize the treatment outcome as follows: 'symptom free' if the result was negative, 'symptom persistent' if the result remained positive after performing the maneuver 3 times or 'canal conversion' if horizontal nystagmus was evoked. RESULTS: Of the patients in the SSM and MSM groups, 78.4 and 91.5% became symptom free, respectively, while canal conversion occurred in 13.8 and 5.1%, respectively (p = 0.003, chi(2) test). The success rate after performing the maneuver once was 57.1% in the MSM and 32.3% in the SSM symptom-free patients (p = 0.001, chi(2) test). One month after the treatment, 22.0 and 9.6% of the SSM and MSM patients had symptom relapse, respectively (p = 0.007, chi(2) test). CONCLUSIONS: More accelerations and a smaller rotation angle improved the effectiveness and efficiency of the repositioning maneuvers and reduced canal conversion. PMID- 26682916 TI - An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design. AB - Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated. PMID- 26682917 TI - Klein tunneling of helical edge states in narrow strips of a two-dimensional topological insulator. AB - The quantum transmission of helical edge states across a square potential barrier is numerically investigated in narrow channels of a two-dimensional topological insulator. Although the transmission probability in general decreases when a potential offset is introduced in the middle of the channels, the transmission remains almost perfect regardless of the amplitude and length of the potential offset when the hybridization energy gap is closed by tuning the off-diagonal spin-orbit terms in the effective four-band Hamiltonian. The approximate absence of scattering resembling the Klein tunneling, where the transmission is unimpeded as an electron propagates relativistically as a hole in the barrier without decay, improves further when an interference condition is satisfied within the barrier. The dependence of the residual reflection on the Fermi level reveals anomalous characteristics in the Klein tunneling regime. PMID- 26682918 TI - High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED. AB - Profiling microbial community function from metagenomic sequencing data remains a computationally challenging problem. Mapping millions of DNA reads from such samples to reference protein databases requires long run-times, and short read lengths can result in spurious hits to unrelated proteins (loss of specificity). We developed ShortBRED (Short, Better Representative Extract Dataset) to address these challenges, facilitating fast, accurate functional profiling of metagenomic samples. ShortBRED consists of two components: (i) a method that reduces reference proteins of interest to short, highly representative amino acid sequences ("markers") and (ii) a search step that maps reads to these markers to quantify the relative abundance of their associated proteins. After evaluating ShortBRED on synthetic data, we applied it to profile antibiotic resistance protein families in the gut microbiomes of individuals from the United States, China, Malawi, and Venezuela. Our results support antibiotic resistance as a core function in the human gut microbiome, with tetracycline-resistant ribosomal protection proteins and Class A beta-lactamases being the most widely distributed resistance mechanisms worldwide. ShortBRED markers are applicable to other homology-based search tasks, which we demonstrate here by identifying phylogenetic signatures of antibiotic resistance across more than 3,000 microbial isolate genomes. ShortBRED can be applied to profile a wide variety of protein families of interest; the software, source code, and documentation are available for download at http://huttenhower.sph.harvard.edu/shortbred. PMID- 26682919 TI - Renal Cell Carcinomas in Vinylidene Chloride-exposed Male B6C3F1 Mice Are Characterized by Oxidative Stress and TP53 Pathway Dysregulation. AB - Vinylidene chloride (VDC) has been widely used in the production of plastics and flame retardants. Exposure of B6C3F1 mice to VDC in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increases in renal cell hyperplasia, renal cell adenoma, and renal cell carcinomas (RCCs). Among those differentially expressed genes from controls and RCC of VDC-exposed mice, there was an overrepresentation of genes from pathways associated with chronic xenobiotic and oxidative stress as well as c-Myc overexpression and dysregulation of TP53 cell cycle checkpoint and DNA damage repair pathways in RCC. Trend analysis comparing RCC, VDC-exposed kidney, and chamber control kidney showed a conservation of pathway dysregulation in terms of overrepresentation of xenobiotic and oxidative stress, and DNA damage and cell cycle checkpoint pathways in both VDC-exposed kidney and RCC, suggesting that these mechanisms play a role in the pathogenesis of RCC in VDC-exposed mice. PMID- 26682920 TI - Post-September 11, 2001, Incidence of Systemic Autoimmune Diseases in World Trade Center-Exposed Firefighters and Emergency Medical Service Workers. AB - OBJECTIVE: To estimate the incidence of selected systemic autoimmune diseases (SAIDs) in approximately 14,000 male rescue/recovery workers enrolled in the Fire Department of the City of New York (FDNY) World Trade Center (WTC) Health Program and to compare FDNY incidence to rates from demographically similar men in the Rochester Epidemiology Project (REP), a population-based database in Olmsted County, Minnesota. PATIENTS AND METHODS: We calculated incidence for specific SAIDs (rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and others) and combined SAIDs diagnosed from September 12, 2001, through September 11, 2014, and generated expected sex- and age-specific rates based on REP rates. Rates were stratified by level of WTC exposure (higher vs lower). Standardized incidence ratios (SIRs), which are the ratios of the observed number of cases in the FDNY group to the expected number of cases based on REP rates, and 95% CIs were calculated. RESULTS: We identified 97 SAID cases. Overall, FDNY rates were not significantly different from expected rates (SIR, 0.97; 95% CI, 0.77-1.21). However, the lower WTC exposure group had 9.9 fewer cases than expected, whereas the higher WTC exposure group had 7.7 excess cases. CONCLUSION: Most studies indicate that the healthy worker effect reduces the association between exposure and outcome by about 20%, which we observed in the lower WTC exposure group. Overall rates masked differences in incidence by level of WTC exposure, especially because the higher WTC exposure group was relatively small. Continued surveillance for early detection of SAIDs in high WTC exposure populations is required to identify and treat exposure-related adverse effects. PMID- 26682921 TI - Cardiac Rehabilitation Program Adherence and Functional Capacity Among Women: A Randomized Controlled Trial. AB - OBJECTIVE: To compare program adherence and functional capacity between women referred to supervised mixed-sex, supervised women-only, or home-based cardiac rehabilitation (CR). PATIENTS AND METHODS: Cardiac Rehabilitation for Heart Event Recovery (CR4HER) was a single-blind, 3 parallel-arm, pragmatic randomized controlled trial. The study took place between November 1, 2009, and July 31, 2013. Low-risk patients with coronary artery disease were recruited from 6 hospitals in Ontario, Canada. Consenting participants completed a preprogram survey, and clinical data were extracted from charts. Participants were referred to CR at 1 of 3 sites. After intake assessment, including a graded exercise stress test, eligible patients were randomized to supervised mixed-sex, supervised women-only, or home-based CR. Six months later, CR adherence and exit assessment data were ascertained. RESULTS: Of the 264 consenting patients, 169 (64.0%) were eligible and randomized. Twenty-seven (16.0%) did not attend, and 43 (25.4%) attended a different model. Program adherence was moderate overall (54.46%+/-35.14%). Analysis of variance revealed no significant differences based on per-protocol analysis (P=.63), but as-treated, home-based participants attended significantly more than did women-only participants (P<.05). Overall, there was a significant increase in functional capacity preprogram to postprogram (P<.001). Although there were no significant differences in functional capacity by model at CR exit based on per-protocol analysis, there was a significant difference on an as-treated basis, which sustained adjustment. Women attending mixed-sex CR attained significantly higher post-CR functional capacity than did women attending home-based programs (P<.05). CONCLUSION: Offering women alternative program models may not promote greater CR adherence or functional capacity; however, replication is warranted. Other proven strategies such as action planning and self-monitoring should be applied. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01019135. PMID- 26682922 TI - CRASP: CFP reconstitution across synaptic partners. AB - Mapping the pattern of connectivity between neurons is widely regarded to be critical for understanding the nervous system. GRASP (GFP reconstitution across synaptic partners) has been used as a promising method for mapping neuronal connectivity, but is currently available in the green color only, limiting its potential applications. Here we demonstrate CRASP (CFP reconstitution across synaptic partners), a cyan-colored version of GRASP. We validated the system in HEK 293T cells, and generated transgenic Drosophila lines to show that the system could reliably detect neuronal contacts in the brain. Furthermore, we showed that the CRASP signal could be selectively amplified using standard immunohistochemistry methods. The CRASP system adds to the toolkit available to researchers for mapping neuronal connectivity, and substantially expands the potential application of GRASP-like strategies. PMID- 26682923 TI - Compound C inhibits macrophage chemotaxis through an AMPK-independent mechanism. AB - Macrophage infiltration in adipose tissue is a well-established cause of obesity linked insulin resistance. AMP-activated protein kinase (AMPK) activation in peripheral tissues such as adipose tissue has beneficial effects on the protection against obesity-induced insulin resistance, which is mainly mediated by prevention of adipose tissue macrophage infiltration and inflammation. In examining the role of AMPK on adipose tissue inflammation, we unexpectedly found that compound C (CC), despite its inhibition of AMPK, robustly inhibited macrophage chemotaxis in RAW 264.7 cells when adipocyte conditioned medium (CM) was used as a chemoattractant. Here, we report that CC inhibition of macrophage migration occurred independently of AMPK. Mechanistically, this inhibitory effect of cell migration by CC was mediated by inhibition of the focal adhesion kinase, AKT, nuclear factor kappaB pathways. Moreover, the expression of chemokine monocyte chemoattractant protein-1 and pro-inflammatory genes such as tumor necrosis factor alpha and inducible nitric oxide synthase were prevented by CC treatment in RAW 264.7 cells stimulated with either adipocyte CM or lipopolysaccharide. Lastly, in accord with the findings of the anti-inflammatory effect of CC, we demonstrated that CC functioned as a repressor of macrophage CM mediated insulin resistance in adipocytes. Taken together, our results suggest that CC serves as a useful inhibitory molecule against macrophage chemotaxis into adipose tissue and thus might have therapeutic potential for the treatment of obesity-linked adipose inflammation. PMID- 26682924 TI - Catalytic site of human protein-glucosylgalactosylhydroxylysine glucosidase: Three crucial carboxyl residues were determined by cloning and site-directed mutagenesis. AB - Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG; EC3.2.1.107) cleaves glucose from disaccharide unit (Glc-alpha1,2-Gal) linked to hydroxylysine residues of collagen. In the present paper we first show that PGGHG is the product of ATHL1 gene as follows. (1) PGGHG was purified from chick embryos and digested with trypsin. LC-MS/MS analysis suggested the tryptic-peptides were from the ATHL1 gene product. (2) Chick embryo ATHL1 cDNA was cloned to a cloning and expression vector and two plasmid clones with different ATHL1 CDS insert were obtained. (3) Each plasmid DNA was transformed into Escherichia coli cells for expression and two isoforms of chicken PGGHG were obtained. (4) Both isoforms effectively released glucose from type IV collagen. Next, we searched for carboxyl residues crucial for catalytic activity as follows; human ATHL1 cDNA was cloned into a cloning and expression vector and 18 mutants were obtained by site directed mutagenesis for 15 carboxyl residues conserved in ATHL1 of jawed vertebrates. The expression analysis indicated that substitutions of Asp301, Glu430 and Glu574 with sterically conservative (D301N, E430Q, E574Q) or functionally conservative (D301E, E430D, E574D) residues led to the complete elimination of enzyme activity. These findings lead us to the conclusion that PGGHG is encoded by ATHL1 and three carboxyl residues (corresponding to Asp301, Glu430 and Glu574 of human PGGHG) might be involved in the catalytic site of PGGHG. PMID- 26682925 TI - DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high fat diet-induced NASH mouse model. AB - Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. PMID- 26682926 TI - Cathepsin D in pancreatic acinar cells is implicated in cathepsin B and L degradation, but not in autophagic activity. AB - Cathepsin D (CD) is the major lysosomal aspartic protease and is widely distributed in the cells of various mammalian tissues. CD participates in various physiological events such as regulation of programmed cell death, activation of enzymatic precursors, and metabolic degradation of intracellular proteins through macroautophagy. To investigate the role of CD in pancreatic acinar cells, which constitute the exocrine pancreas, we generated and examined mice specifically deficient for CD in pancreatic acinar cells. CD deficient mice showed normal pancreatic development and autophagic activity, although LC3-II, which is a marker of the autophagosome, accumulates in both physiological and pancreatitis conditions. Moreover, CD deficiency leads to accumulation of matured cathepsin B (CB) and cathepsin L (CL) which are members of the cysteine protease family. We therefore conclude that CD in pancreatic acinar cells is implicated in CB and CL degradation but not in autophagic activity. PMID- 26682927 TI - A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis. AB - NOTCH1 plays an important role in epithelial differentiation and carcinogenesis. To investigate the impact of Notch1 inactivation in oroesophageal epithelium, we generated conditional knockout (cKO) mice, using a combined construct which induces the expression of single guide RNA targeting Notch1 and Cas9 by the KRT14 promoter. The cKO mice exhibited patchy hair loss and multiple NOTCH1-negative areas in the tongue epithelium, indicative of heterogeneous knockout. The cKO mice showed susceptibility to esophageal tumorigenesis, underscoring Notch1 as a tumor suppressor. Our one-step strategy for generation of cKO mice provides a versatile method to examine a gene function in vivo. PMID- 26682928 TI - MicroRNA-181c inhibits glioblastoma cell invasion, migration and mesenchymal transition by targeting TGF-beta pathway. AB - MicroRNAs (miRNAs) are small non-coding RNAs frequently dysregulated in human malignancies. In this study, we found that miR-181c was down-regulated both in glioblastoma tissues and cell lines. We also annotated 566 TCGA miRNA expression profiles and found that patients with high microRNA-181c (miR-181c)-expressing tumors had significantly longer OS and PFS. Overexpression of miR-181c evidently inhibited glioblastoma cell line T98G migration and invasion. Further, the expression of E-cadherin was significantly upregulated and that of N-cadherin and vimentin was significantly down-regulated. We also found that miR-181c overexpression inhibited TGF-beta signaling by down-regulating TGFBR1, TGFBR2 and TGFBRAP1 expression. Overall, our study found that miR-181c plays a key role in glioblastoma cell invasion, migration and mesenchymal transition suggesting potential therapeutic applications. PMID- 26682929 TI - Barriers to implementation of opioid overdose prevention programs in Ohio. AB - BACKGROUND: Nationally, overdose fatalities have reached epidemic proportions. Ohio has one of the highest overdose death rates in the country, as well as high rates of prescription opioid trafficking. METHODS: A cross-sectional self-report survey of opioid overdose prevention programs (OOPPs) in Ohio was conducted between August and October 2014 to characterize programs and ascertain barriers to successful implementation. A 91% response rate was achieved with 18 programs participating in the study. RESULTS: The first Ohio OOPP opened in August 2012, a second program opened in 2013, and the remaining programs began in 2014. All of the programs distribute nasal naloxone and provide overdose prevention education, and 89% (n = 16) provide overdose kits for free. Six OOPPs are funded by the Ohio Department of Health, 3 programs are funded by a local health foundation, and several other public and private funding sources were reported. The OOPPs have funding to distribute a combined total of 8,670 overdose kits and had distributed 1998 kits by October 2014. The OOPPs reported 149 overdose reversals. Fifteen programs (83%) reported implementation barriers that were categorized as stigma-, cost-, staffing-, legal, regulatory, and client-related problems. Legislative changes aimed at removing some of the obstacles to distribution and lay administration of naloxone have recently been enacted in Ohio. CONCLUSIONS: OOPPs have rapidly expanded in Ohio during the past 3 years. Although recent legislative changes have addressed some of the reported implementation barriers, stigma and the cost of naloxone remain significant problems. PMID- 26682930 TI - Homoleptic Two-Coordinate Silylamido Complexes of Chromium(I), Manganese(I), and Cobalt(I). AB - Anionic two-coordinate complexes of first-row transition-metal(I) centres are rare molecules that are expected to reveal new magnetic properties and reactivity. Recently, we demonstrated that a N(SiMe3)2(-) ligand set, which is unable to prevent dimerisation or extraneous ligand coordination at the +2 oxidation state of iron, was nonetheless able to stabilise anionic two-coordinate Fe(I) complexes even in the presence of a Lewis base. We now report analogous Cr(I) and Co(I) complexes with exclusively this amido ligand and the isolation of a [Mn(I){N(SiMe3)2}2]2(2-) dimer that features a Mn-Mn bond. Additionally, by increasing the steric hindrance of the ligand set, the two-coordinate complex [Mn(I){N(Dipp)(SiMe3)}2](-) was isolated (Dipp=2,6-iPr2-C6H3). Characterisation of these compounds by using X-ray crystallography, NMR spectroscopy, and magnetic susceptibility measurements is provided along with ligand-field analysis based on CASSCF/NEVPT2 ab initio calculations. PMID- 26682931 TI - Orientation Control in Thin Films of a High-chi Block Copolymer with a Surface Active Embedded Neutral Layer. AB - Directed self-assembly (DSA) of block copolymers (BCPs) is an attractive advanced patterning technology being considered for future integrated circuit manufacturing. By controlling interfacial interactions, self-assembled microdomains in thin films of polystyrene-block-poly(methyl methacrylate), PS-b PMMA, can be oriented perpendicular to surfaces to form line/space or hole patterns. However, its relatively weak Flory interaction parameter, chi, limits its capability to pattern sub-10 nm features. Many BCPs with higher interaction parameters are capable of forming smaller features, but these "high-chi" BCPs typically have an imbalance in surface energy between the respective blocks that make it difficult to achieve the required perpendicular orientation. To address this challenge, we devised a polymeric surface active additive mixed into the BCP solution, referred to as an embedded neutral layer (ENL), which segregates to the top of the BCP film during casting and annealing and balances the surface tensions at the top of the thin film. The additive comprises a second BCP with a "neutral block" designed to provide matched surface tensions with the respective polymers of the main BCP and a "surface anchoring block" with very low surface energy that drives the material to the air interface during spin-casting and annealing. The surface anchoring block allows the film to be annealed above the glass transition temperature of the two materials without intermixing of the two components. DSA was also demonstrated with this embedded neutral top layer formulation on a chemical patterned template using a single step coat and simple thermal annealing. This ENL technology holds promise to enable the use of high chi BCPs in advanced patterning applications. PMID- 26682932 TI - Diastolic Dysfunction Is a Contributing Factor to Exercise Intolerance in COPD. AB - Right ventricular (RV) systolic failure is rare in patients with COPD, but they often develop RV diastolic dysfunction. Left ventricular (LV) diastolic dysfunction is also common in this population. Nevertheless, data are scarce regarding the effect of diastolic dysfunction on the functional capacity in patients with COPD. We investigated the correlation between echocardiographic parameters of RV and LV diastolic function and the exercise capacity in COPD, by using conventional echocardiographic methods and tissue Doppler imaging. 65 patients with COPD (61 +/- 9 years) in stages GOLD II-IV were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Right (RA) and left atrial (LA) area index were measured; collapsibility index inferior vena cava was calculated. Parameters of the mitral and tricuspid inflow (E, A) as well as annular systolic (S), early- (e') and late- (a') diastolic myocardial longitudinal velocities were measured. E/A, E/e' and e'/a' ratios were calculated. 6MWT distance was 330 +/- 76 m. LV diastolic dysfunction was found in 48 (74%) patients. LV and RV filling pressures were elevated in 28 (43%) and in 29 (45%) patients, respectively. In the left heart, LA area index showed significant correlation with the functional capacity (r = -0.319; p = 0.011). In stepwise multiple linear regression analysis tricuspid e'/a' (r = 0.611; p = 0.000), collapsibility index (r = 0.505; p = 0.000), RA area index (r = -0.445; p = 0.000) and body surface area (r = 0.314; p = 0.011) were independent predictors of 6MWT distance. Right ventricular diastolic function and filling pressure have strong influence on the functional capacity in patients with COPD. PMID- 26682933 TI - Biointeractions of C.I. Acid Red 2 and its structural analogues with transporter albumin: Fluorescence, circular dichroism, and ligand docking approaches. AB - In this contribution, the toxicological effects of C.I. Acid Red 2 and 1-(2 pyridylazo)-2-naphthol (PAN) have been elucidated by utilizing plasma albumin as a biological model. Fluorescence data indicated that the Trp-214 residue was quenched by both azo compounds, but the quenching degree of C.I. Acid Red 2 is less than PAN. According to the results of time-resolved fluorescence decay, it may be observed that the quenching of Trp-214 residue is controlled by static type; this corroborates the Stern-Volmer analyses and the conformational transition of protein was concurred. The experiments also found that azo colorants are situated within subdomain IIA, several amino acid residues, such as Ser-202, Ala-210, and Trp-214 were believed to be yielded direct interaction with the two chemicals, yet the operating distances between C.I. Acid Red 2 and relevant residues are greater than PAN. Interestingly, we may ascertain that the azo colorants with naphthalene ring possess stronger affinity with protein than those just having benzene ring in their molecular structure. This suggested that the existence of naphthalene ring substituent could hold relatively great risk for the human body due to large hydrophobicity (cLogP); therefore, the hydrophobicity of azo colorants can probably be a major element of its toxicological activities. PMID- 26682934 TI - Revealing Stepwise Mechanisms in Dipolar Cycloaddition Reactions: Computational Study of the Reaction between Nitrones and Isocyanates. AB - The mechanism of cycloaddition reactions of nitrones with isocyanates has been studied using density functional theory (DFT) methods at the M06-2X/cc-pVTZ level of theory. The exploration of the potential energy surfaces associated with two reactive channels leading to 1,2,4-oxadiazolidin-5-ones and 1,4,2-dioxazolidines revealed that the cycloaddition reaction takes place through a concerted mechanism in gas phase and in apolar solvents but a stepwise mechanism in polar solvents. In stepwise mechanisms, the first step of the reaction is a rare case in which the nitrone oxygen acts as a nucleophile by attacking the central carbon atom of the isocyanate (interacting with the pi-system of the C?O bond) to give an intermediate. The corresponding transition structure is stabilized by an attractive electrostatic interaction favored in a polar medium. The second step of the reaction is the rate-limiting one in which the formation of 1,2,4 oxadiazolidin-5-ones or 1,4,2-dioxazolidines is decided. Calculations indicate that formation of 1,2,4-oxadiazolidin-5-ones is favored both kinetically and thermodynamically independently of the solvent, in agreement with experimental observations. Noncovalent interactions (NCI) and topological analysis of the gradient field of electron localization function (ELF) bonding confirmed the observed interactions. PMID- 26682935 TI - Erectile dysfunction in heart failure rats is associated with increased neurogenic contractions in cavernous tissue and internal pudendal artery. AB - AIMS: The rates of erectile dysfunction (ED) in heart failure (HF) are extremely high. This study tested the hypothesis that rats with HF display ED and that HF leads to increased sympathetic-mediated contractile tone of the cavernous tissue and/or internal pudendal arteries (IPA) as potential mechanisms contributing to ED. MAIN METHODS: HF was induced in Wistar rats by ligation of the left anterior descending coronary artery. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of major pelvic ganglion were determined in vivo. Cavernosal and IPA contractions were induced by electric field stimulation (EFS) and phenylephrine. RhoA, Rho kinase 2 (ROCK 2) and myosin phosphatase target protein 1 (MYPT-1) protein expression and phosphorylation levels were also determined. KEY FINDINGS: HF rats display impaired erectile function represented by decreased ICP/MAP responses. EFS-mediated contractions were increased by HF in cavernous tissue and IPA. Contractions induced by phenylephrine were increased in cavernous tissue of HF rats, but decreased in IPA rings. Moreover, HF decreased RhoA protein expression, but increased ROCK 2 and MYPT-1 phosphorylation levels in cavernous tissue. In conclusion, rats with HF induced by myocardial infarction display ED in vivo and increased sympathetic mediated contractile responses in cavernous tissue and IPA. Increased sympathetic mediated contractile responses were associated with increased ROCK 2 and MYPT-1 phosphorylation in cavernosal tissue, suggesting the involvement of ROCK signaling pathway in ED genesis. SIGNIFICANCE: Our findings suggest new mechanisms linking HF to ED, providing potential therapeutic targets for treating ED associated to HF. PMID- 26682936 TI - Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. AB - AIMS: Interleukin-10 (IL-10) is a multi-functional cytokine with potent anti inflammatory properties. We hypothesized that IL-10 limits increased RhoA/Rho kinase signaling and vascular reactivity in arteries from angiotensin II (Ang II) hypertensive mice. MAIN METHODS: Wild type (WT) and IL-10 knockout ((-/-)) mice were infused with Ang II (90ng/min) for 14days. Additionally, WT mice were infused with Ang II and simultaneously infused with exogenous IL-10 (0.5etag/min, 14days). Aortic rings were mounted in a myograph and concentration-response curve to phenylephrine (PE) were evaluated. KEY FINDINGS: After Ang II infusion, blood pressure responses, but not maximal contraction to PE, was greater in IL-10(-/-) mice, compared to WT. Rho-kinase inhibition (Y-27632; 10MUM) resulted in a more evident reduction of PE-induced contraction in WT hypertensive mice, when compared to IL-10(-/-) hypertensive mice. IL-10 exogenous infusion prevented the blood pressure increase in Ang II-infused WT mice. The augmented PE-contraction observed in aorta from WT mice infused with Ang II was also prevented by exogenous infusion of IL-10. Additionally, Rho-kinase inhibition (Y-27632; 10MUM) abolished the differences in the contractile response to PE between these groups. SIGNIFICANCE: These results demonstrate that IL-10 counteracts both the pressoric activity of Ang II as well as vascular dysfunction associated with hypertension, partially, modulating the RhoA-Rho kinase pathway. Strategies to enhance IL-10 levels during hypertension may enhance the benefits provided by regular treatments. PMID- 26682937 TI - Two-photon imaging of endothelin-1-mediated intracellular Ca(2+) handling in smooth muscle cells of rat renal resistance arteries. AB - AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor which regulates the physiology of cardiorenal system. The aim of this study was to evaluate ET-1 mediated elevation of intracellular Ca(2+) in smooth muscle cells (SMC) of renal resistance arteries. MAIN METHODS: In in vitro studies of primary SMC, which were isolated from rat renal microvessels, the levels of intracellular Ca(2+) were calculated from the ratio of emissions at 340 and 380nm after loading cells with Fura 2-AM dye. In ex vivo studies we used two-photon imaging of renal resistance arteries excised from rat kidneys and loaded with fluorescent Ca(2+) indicator Fluo-4 AM. KEY FINDINGS: The two-photon imaging demonstrates that treatment of isolated rat renal resistance arteries with ET-1 causes a rapid increase of intracellular Ca(2+) concentration in smooth muscle vasculature of these vessels. These ex vivo observations are in accordance with in vitro findings indicating that ET-1 mediates activation of TRPC channels and increases the level of intracellular Ca(2+) in cultured SMC to 510+/-83nM. SIGNIFICANCE: ET-1-mediated elevation of intracellular Ca(2+) is strongly linked to renal microvascular contraction and is crucial for ET-1-induced contraction of SMC. The two-photon imaging of intracellular Ca(2+) in intact SMC of rat renal resistance arteries is a powerful technique which allows the detailed ex vivo analysis of intracellular Ca(2+) handling by ET-1, an important player in hypertension-related kidney diseases. PMID- 26682938 TI - Human cardiomyocyte generation from pluripotent stem cells: A state-of-art. AB - The human heart is considered a non-regenerative organ. Worldwide, cardiovascular diseases continue to be the leading cause of death. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate human CMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular-, and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large scale suspension culture differentiation, and development of chemically defined culture conditions. These hCMs could be useful particularly in the context of in vitro disease modeling, pharmaceutical screening and in cellular replacement therapies once the safety issues are overcome. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and current limitations. PMID- 26682939 TI - Distribution of acotiamide, an orally active acetylcholinesterase inhibitor, into the myenteric plexus of rat and dog stomachs. AB - AIMS: Acotiamide is the first-in-class drug for the treatment of functional dyspepsia. Although pharmacological and therapeutic actions of acotiamide are thought to be derived from its inhibitory effects on acetylcholinesterase (AChE), whether the concentration of acotiamide at the site of action is sufficient to inhibit AChE remains unclear. Since major site of acotiamide action is thought to be the cholinergic nerve terminals in gastric myenteric plexus, we studied the distribution of [(14)C]acotiamide into gastric myenteric plexus. MAIN METHODS: Distribution of [(14)C]acotiamide was evaluated using macro- and micro autoradiography in rats and dogs. KEY FINDINGS: The results of macro autoradiography showed the concentration of radioactivity was 27.9MUM in rat stomach, which was 12 times higher than IC50 of acotiamide for rat AChE. Being different from rats, the distribution of radioactivity in the muscular layer was distinguishable from that in the mucosal layer in dog stomach. The concentration of radioactivity in the muscular layer of dog stomach (1.41MUM) was approximately two-times lower than those in the mucosal layer, however, it was approximately 1.2 times higher than IC50 of acotiamide for dog AChE. The results of micro autoradiography also showed the radioactivity distributed homogenously in the muscular layer of rat stomach, suggesting the concentration of radioactivity around the ganglion of myenteric plexus is similar to that in the muscular layer of stomach. SIGNIFICANCE: These findings suggest acotiamide distributes to the myenteric plexus of stomach, a putative site of acotiamide action, with adequate concentrations to inhibit AChE, in both of rat and dog stomachs. PMID- 26682940 TI - An unexpected and forbidding complication after total hip arthroplasty. PMID- 26682941 TI - Giant synovial chondromatosis of the metacarpophalangeal joint. PMID- 26682943 TI - Inhibitory potential of tuberculosis drugs on ATP-binding cassette drug transporters. AB - BACKGROUND: Multiple-drug therapy for tuberculosis (TB) and TB-associated co morbidity increase the likelihood of drug-drug interactions (DDIs). Inhibition of membrane transporters is an important mechanism underlying DDIs. In this study, we assessed the in vitro inhibitory potential of currently used first and second line TB drugs and of proposed mycobacterial efflux pump inhibitors (EPIs) on the major ABC transporters relevant to drug transport, namely P-gp, BCRP, BSEP and MRP1-5. METHODS: Membrane vesicles isolated from transporter-overexpressing HEK293 cells were used to study the inhibitory action of TB drugs and EPIs on the transport of model substrates [(3)H]-NMQ (P-gp); [(3)H]-E1S (BCRP); [(3)H]-TCA (BSEP); [(3)H]-E217betaG (MRP1, 3 and 4) and [(3)H]-MTX (MRP2 and 5). RESULTS: A strong inhibition (IC50 value <15 MUM) was observed for clofazimine (P-gp, BCRP and MRP1), thioridazine (BCRP), timcodar (P-gp, BSEP and MRP1) and SQ109 (P-gp and BCRP). Rifampicin inhibited all transporters, but less potently. CONCLUSIONS: Co-administration of clofazimine, thioridazine, timcodar, SQ109 and possibly rifampicin with drugs that are substrates for the inhibited transporters may lead to DDIs. The mycobacterial EPIs potently inhibited a wider range of human ABC transporters than previously reported. These vesicular transport data are especially valuable considering the current emphasis on development of TB drug regimens. PMID- 26682942 TI - Hu antigen R is required for NOX-1 but not NOX-4 regulation by inflammatory stimuli in vascular smooth muscle cells. AB - OBJECTIVE: NOX-1 and NOX-4 are key enzymes responsible for reactive oxygen species (ROS) generation in vascular smooth muscle cells (VSMC). The RNA-binding protein Hu antigen R (HuR) is implicated in posttranscriptional regulation of gene expression; however, its role regulating NOX is unknown. We investigated transcriptional and posttranscriptional mechanisms underlying angiotensin II (AngII) and IL-1beta regulation of NOX-1 and NOX-4 in VSMC and their implications in cell migration. METHODS: Rat and human VSMC were stimulated with AngII (0.1 MUmol/l) and/or IL-1beta (10 ng/ml). NOX-1 and NOX-4 mRNA and protein levels, NOX 1 and NOX-4 promoter and 3'UTR activities, NADPH oxidase activity, ROS production, and cell migration were studied. RESULTS: IL-1beta increased NOX-1 expression, NADPH oxidase activity and ROS production, and decreased NOX-4 expression and H2O2 production in VSMC. AngII potentiated the IL-1beta-mediated induction of NOX-1 expression, NADPH oxidase activity, ROS production, and cell migration. However, AngII did not influence IL-1beta-induced NOX-4 downregulation. AngII + IL-1beta interfered with the decay of NOX-1 mRNA and promoted HuR binding to NOX-1 mRNA. Moreover, HuR blockade reduced NOX-1 mRNA stability and AngII + IL-1beta-induced NOX-1 mRNA levels. IL-1beta decreased NOX 4 expression through a transcriptional mechanism that involved response elements situated in the proximal promoter. AngII and/or IL-1beta-induced cell migration were prevented by NOX-1 and HuR blockade and were augmented by NOX-4 overexpression. CONCLUSION: In VSMC HuR-mediated mRNA stabilization is partially responsible for AngII + IL-1beta-dependent NOX-1 expression, whereas transcriptional mechanisms are involved in decreased NOX-4 expression induced by IL-1beta. NOX4 and HuR regulation of NOX-1 contributes to VSMC migration, important in vascular inflammation and remodeling. PMID- 26682944 TI - Why is the South Orkney Island shelf (the world's first high seas marine protected area) a carbon immobilization hotspot? AB - The Southern Ocean archipelago, the South Orkney Islands (SOI), became the world's first entirely high seas marine protected area (MPA) in 2010. The SOI continental shelf (~44 000 km(2) ), was less than half covered by grounded ice sheet during glaciations, is biologically rich and a key area of both sea surface warming and sea-ice losses. Little was known of the carbon cycle there, but recent work showed it was a very important site of carbon immobilization (net annual carbon accumulation) by benthos, one of the few demonstrable negative feedbacks to climate change. Carbon immobilization by SOI bryozoans was higher, per species, unit area and ice-free day, than anywhere-else polar. Here, we investigate why carbon immobilization has been so high at SOI, and whether this is due to high density, longevity or high annual production in six study species of bryozoans (benthic suspension feeders). We compared benthic carbon immobilization across major regions around West Antarctica with sea-ice and primary production, from remotely sensed and directly sampled sources. Lowest carbon immobilization was at the northernmost study regions (South Georgia) and southernmost Amundsen Sea. However, data standardized for age and density showed that only SOI was anomalous (high). High immobilization at SOI was due to very high annual production of bryozoans (rather than high densities or longevity), which were 2x, 3x and 5x higher than on the Bellingshausen, South Georgia and Amundsen shelves, respectively. We found that carbon immobilization correlated to the duration (but not peak or integrated biomass) of phytoplankton blooms, both in directly sampled, local scale data and across regions using remote-sensed data. The long bloom at SOI seems to drive considerable carbon immobilization, but sea-ice losses across West Antarctica mean that significant carbon sinks and negative feedbacks to climate change could also develop in the Bellingshausen and Amundsen seas. PMID- 26682945 TI - Condylar resorption after orthognathic surgery: A systematic review. AB - INTRODUCTION: Condylar resorption after orthognathic surgery (CROS) represents a progressive alteration of shape and volume of the mandibular condyle. It is a known factor of surgical relapse. The aim of this systematic review was to discuss the physiopathology, mechanisms, risk factors, diagnosis and treatment of this disease. MATERIALS AND METHODS: A systematic review of the literature was performed on the Pubmed database from 1970 to 2014, using following terms: ("orthognathic surgery") AND ("condylar resorption" OR "progressive condylar resorption" OR "idiopathic condylar resorption" OR "condylar atrophy" OR "condylolysis"). Papers were included according inclusion and exclusion criterias. RESULTS: The search leaded to 32 articles. Seventeen were included. CROS was a condylar remodeling secondary to an imbalance between mechanical stress applied to the temporomandibular joints (TMJ) and the host adaptive capacities. It mainly occurred in 14 to 50years old women with pre-existing TMJ dysfunction, estrogen deficiency, class II malocclusion with a high mandibular plane angle, a diminished posterior facial height and a posteriorly inclined condylar neck. Mandibular advancement superior to 10mm, counterclockwise rotation of the mandible and posteriorly condylar repositioning were associated with an increased risk of CROS. DISCUSSION: Treatment consists in re-operation in case of degradation of the occlusal result after an inactivity period of at least 6 months. Condylectomy with allogenic or autologous reconstruction is an alternative. Prevention is crucial and requires at-risk patient information. PMID- 26682946 TI - Enhanced Glucose Transport, but not Phosphorylation Capacity, Ameliorates Lipopolysaccharide-Induced Impairments in Insulin-Stimulated Muscle Glucose Uptake. AB - Lipopolysaccharide (LPS) is known to impair insulin-stimulated muscle glucose uptake (MGU). We determined if increased glucose transport (GLUT4) or phosphorylation capacity (hexokinase II; HKII) could overcome the impairment in MGU. We used mice that overexpressed GLUT4 (GLUT4) or HKII (HK) in skeletal muscle. Studies were performed in conscious, chronically catheterized (carotid artery and jugular vein) mice. Mice received an intravenous bolus of either LPS (10 MUg/g body weight) or vehicle (VEH). After 5 h, a hyperinsulinemic-euglycemic clamp was performed. As MGU is also dependent on cardiovascular function that is negatively affected by LPS, cardiac function was assessed using echocardiography. LPS decreased whole body glucose disposal and MGU in wild-type (WT) and HK mice. In contrast, the decrease was attenuated in GLUT4 mice. Although membrane associated GLUT4 was increased in VEH-treated GLUT4 mice, LPS impaired membrane associated GLUT4 in GLUT4 mice to the same level as LPS-treated WT mice. This suggested that overexpression of GLUT4 had further benefits beyond preserving transport activity. In fact, GLUT4 overexpression attenuated the LPS-induced decrease in cardiac function. The maintenance of MGU in GLUT4 mice following LPS was accompanied by sustained anaerobic glycolytic flux as suggested by increased muscle Pdk4 expression, and elevated lactate availability. Thus, enhanced glucose transport, but not phosphorylation capacity, ameliorates LPS-induced impairments in MGU. This benefit is mediated by long-term adaptations to the overexpression of GLUT4 that sustain muscle anaerobic glycolytic flux and cardiac function in response to LPS. PMID- 26682948 TI - Fecal Microbiota Transplant Restores Mucosal Integrity in a Murine Model of Burn Injury. AB - The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury. PMID- 26682949 TI - Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice. AB - Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production. We investigated the immunological function of morphine using a mouse model of septic shock. We treated mice with alpha-galactosylceramide (2 MUg/mouse) to induce lethal endotoxic shock following a challenge with lipopolysaccharide (LPS, 1.5 MUg/mouse). This model represents acute lung injury and respiratory failure, and reflects the clinical features of severe septic shock. We evaluated the effect of the timing of morphine (0.8 mg/mouse) administration on the survival rate, cytokine production in vivo, and histological changes of mice with LPS-mediated lethal endotoxic shock. Morphine treatment before LPS challenge suppressed lethal endotoxic shock. In contrast, when we administered after LPS, morphine exacerbated lethal endotoxic shock; hematoxylin and eosin staining revealed a marked increase in the accumulation of infiltrates comprising polymorphonuclear leukocytes and mononuclear cells in the lung; and Elastica van Gieson staining revealed the destruction of alveoli. The plasma levels of tumor necrosis factor alpha, interferon-gamma, monocyte-chemotactic protein-1, and interleukin-12 in the group treated with morphine after LPS challenge were higher than those treated with morphine before LPS challenge. In conclusion, one of the factors that determine whether morphine exacerbates or inhibits infection is the timing of its administration. Morphine treatment before shock improved the survival rate, and morphine treatment after shock decreased the rate of survival. PMID- 26682947 TI - Plasma Mitochondrial DNA--a Novel DAMP in Pediatric Sepsis. AB - Mitochondrial DNA (mtDNA) is a novel danger-associated molecular pattern that on its release into the extracellular milieu acts via toll-like receptor-9, a pattern recognition receptor of the immune system. We hypothesized that plasma mtDNA concentrations will be elevated in septic children, and these elevations are associated with an increase in the severity of illness. In a separate set of in vitro experiments, we test the hypothesis that exposing peripheral blood mononuclear cells (PBMC) to mtDNA activates the immune response and induces tumor necrosis factor (TNF) release. Children with sepsis/systemic inflammatory response syndrome or control groups were enrolled within 24 h of admission to the pediatric intensive care unit. Mitochondrial gene cytochrome c oxidase 1 (COX1) concentrations were measured by real-time quantitative PCR in the DNA extracted from plasma. PBMCs were treated with mtDNA (10 MUg/mL) and supernatant TNF levels were measured. The median plasma mtDNA concentrations were significantly elevated in the septic patients as compared with the critically ill non-septic and healthy control patients [1.75E+05 (IQR 6.64E+04-3.67E+05) versus 5.73E+03 (IQR 3.90E+03-1.28E+04) and 6.64E+03 (IQR 5.22E+03-1.63E+04) copies/MUL respectively]. The median concentrations of plasma mtDNA were significantly greater in patients with MOF as compared with patients without MOF (3.2E+05 (IQR 1.41E+05-1.08E+06) vs. 2.9E+04 (IQR 2.47E+04-5.43E+04) copies/MUL). PBMCs treated with mtDNA demonstrated higher supernatant TNF levels as compared with control cells (6.5 +/- 1.8 vs. 3.5 +/- 0.5 pg/mL, P > 0.05). Our data suggest that plasma mtDNA is a novel danger-associated molecular pattern in pediatric sepsis and appears to be associated with MOF. PMID- 26682950 TI - Time-Series Expression of Toll-Like Receptor 4 Signaling in Septic Mice Treated with Mesenchymal Stem Cells. AB - Sepsis remains an important cause of mortality worldwide, and early deaths resulting from overwhelming inflammation in septic patients have been reported. Vigorous immune reactions are beneficial for bacterial clearance in this circumstance but at the price of self-tissue damage. Mesenchymal stem cells (MSCs) have been found to modulate immune function and attenuate sepsis. As the Toll-like receptor 4 pathway plays an important role in response to infections, here we investigated the mechanisms of MSC-mediated immunomodulation by determining the expression of Toll-like receptor 4 signaling in the liver and by circulating cytokines at 0, 1, 2, 3, and 6 h after cecal ligation and puncture (CLP)-induced sepsis in mice. We found that administration of umbilical cord derived MSCs (UCMSCs) was beneficial for survival. Six hours after CLP, UCMSC administration decreased the expression of MyD88 mRNA and protein in the liver tissues of the mice, and also the ratio of NFkappaB phosphorylation (P = 0.041 and 0.005, respectively). Serum levels of TNF-alpha, MCP-1, IFN-gamma, and IL-6 were significantly lower and IL-10 significantly higher 6 h after CLP in the mice receiving UCMSCs compared with those receiving PBS only. Our study provides the first in vivo evidence for the association of the MyD88-NFkappaB pathway and MSC mediated immunomodulation during sepsis. The immunomodulatory effect of UCMSCs was noted from 3 to 6 h after injection, and the MyD88-NFkappaB pathway played an important role in response to the immunomodulatory signals from UCMSCs. PMID- 26682951 TI - Effect of Histone Acetylation on N-Methyl-D-Aspartate 2B Receptor Subunits and Interleukin-1 Receptors in Association with Nociception-Related Somatosensory Cortex Dysfunction in a Mouse Model of Sepsis. AB - Whole-body inflammation (i.e., sepsis) often results in brain-related sensory dysfunction. We previously reported that interleukin (IL)-1 resulted in synaptic dysfunction of septic encephalopathy, but the underlying molecular mechanisms remain unknown, as do effective treatments. Using mice, we examined immunohistochemistry, co-immunoprecipitation, enzyme-linked immunosorbent assay, and behavior analyses, and investigated the role of the N-methyl-D-aspartate 2B subunit (NR2B) of NMDA receptor, IL-1 receptor, and histone acetylation in the pathophysiology underlying sensory dysfunction induced by lipopolysaccharide (LPS). Mice groups of sham-operated, LPS, LPS with an NR2B antagonist, or LPS with resveratrol (a histone acetylation activator) were analyzed. We found that LPS increased NR2B and interleukin-1 receptor (IL-1R) immunoreactivity. The expression of Iba1, a marker for microglia and/or macrophages, increased more significantly in the brain than in the spinal cord, implicating NR2B and IL-1R in brain inflammation. Immunoprecipitation with NR2B and IL-1R revealed related antibodies. Blood levels of IL-1beta (i.e., the IL-1R ligand) increased, though not significantly, suggesting that inflammation peaked at 20 h. Behavioral assessments of central (CNS) and peripheral sensory (PNS) function indicated that LPS delayed CNS but not PNS escape latency. Finally, NR2B antagonist or resveratrol in the lateral ventricle antagonized the effects of LPS in the brain and improved animal survival. In summary, histone acetylation may control expression of NR2B and IL-1R, alleviating inflammation-induced sensory neuronal dysfunction caused by LPS. PMID- 26682952 TI - Using "residual" FNA rinse and body fluid specimens for next-generation sequencing: An institutional experience. AB - BACKGROUND: Tissue specimens are typically considered optimal for molecular testing; however, in the current era of personalized medicine, cytopathology specimens are increasingly recognized as potential sources for molecular testing. This is often accomplished by using cell block specimens and/or fine-needle aspiration (FNA) smear preparations. In this study, the authors investigated the feasibility, performance, and quality of "residual" FNA rinse and body effusion fluids used for next-generation sequencing (NGS). METHODS: Sequence data were generated from 17 malignancies in 16 patients from 13 FNA (10 lymph nodes, 1 lung, and 2 bone lesions) and 4 effusion (3 pleural and 1 pericardial) specimens. Malignancies included carcinomas (lung, breast, ovarian, and unknown primary), melanoma, and myeloma. Paired NGS testing was performed in 7 patients who had surgical biopsy or cell block specimens available. Routinely processed residual FNA rinse material and body fluids were used for DNA extraction and NGS (targeted gene panel). RESULTS: NGS was successfully performed on all 17 specimens. A significant amount of DNA was obtained from the residual FNA rinse (176.3 ng/MUL) compared with the paired cell block slides (10.6 ng/MUL). Two of the 10 lung adenocarcinomas (20%) demonstrated epidermal growth factor receptor (EGFR) mutations, including 1 leucine-to-arginine substitution at codon 858 (L858R) in exon 21 and 1 codon 2235_2249 deletion (resulting in an in-frame deletion of 5 amino acids from position 746 to 750 [glutamic acid, leucine, arginine, glutamic acid, and alanine]; E746_A750del) in exon 19. Three KRAS [Kirsten rat sarcoma viral oncogene homolog] mutations, 1 BRAF (v-Raf murine sarcoma viral oncogene homolog B1) mutation, and 1 NRAS (neuroblastoma RAS viral oncogene homolog) mutation were identified in the remaining lung adenocarcinomas. Patients who underwent paired testing demonstrated 100% concordant mutations. CONCLUSIONS: Targeted NGS can be performed on residual FNA rinse and body fluid specimens. This approach is particularly important when a paucicellular cell block or biopsy specimen is encountered. Cancer Cytopathol 2016;124:324-29. (c) 2015 American Cancer Society. PMID- 26682953 TI - Dehydroepiandrosterone Stimulation of Osteoblastogenesis in Human MSCs Requires IGF-I Signaling. AB - Dehydroepiandrosterone (DHEA) is an adrenal steroid that circulates in high concentrations in humans in its sulfated form, DHEAS. Clinical and epidemiological studies suggested that low DHEAS levels may be associated with low bone mass. Previously, we and others showed that the effects of DHEA on the skeleton may be conferred partly by their ability to inhibit skeletal catabolic agents, for example, bone resorptive cytokine IL-6. In this study, we tested the hypothesis that the anabolic effects of DHEA on osteoblastogenesis require IGF-I signaling pathways. Using both primary cultures and a cell line of human bone marrow-derived mesenchymal stem cells (hMSCs), we show that DHEA and other steroids stimulate osteoblastogenesis as shown by alkaline phosphatase activity and osteoblast gene induction. The stimulation by DHEA on both IGF-I gene expression and osteoblastogenesis in hMSCs requires IGF-I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. This study adds information to indicate that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL-6 and stimulation of anabolic IGF-I-mediated mechanisms. J. Cell. Biochem. 117: 1769-1774, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26682954 TI - Effects of Simulated Gastric Juice on CAD/CAM Resin Composites-Morphological and Mechanical Evaluations. AB - PURPOSE: To evaluate the effects of simulated gastric juice on CAD/CAM resin composites by means of morphological and mechanical (i.e., hardness) evaluations. MATERIALS AND METHODS: Fourteen specimens of each resin composite (Lava Ultimate and Paradigm MZ100) were prepared according to the manufacturer's instructions. They were submitted to erosive challenges in a simulated gastric juice (pH = 1.2) solution for 6 and 24 hours. Vickers microhardness and surface roughness (Ra , Rq ) evaluations were taken before (baseline) and after acid exposure. Morphological analysis was obtained using scanning electron microscopy (SEM). Statistical analysis was performed using two-way repeated measures ANOVA and Student-Newman Keuls's test (alpha = 0.05). RESULTS: Paradigm MZ100 demonstrated higher microhardness than Lava Ultimate regardless of the storage time period (p <= 0.001), and microhardness was not affected by the acidic challenge (p = 0.58). After 6 hours of acid exposure, a significant decrease in Ra and Rq was seen for Paradigm MZ100 when compared to the baseline (Ra p = 0.032; Rq p = 0.013); however, for Lava Ultimate only Rq decreased (p = 0.021), while Ra remained unchanged (p = 0.38). After 24 hours of acid exposure, while Paradigm MZ100 exhibited no additional changes in surface roughness (p >= 0.75), Lava Ultimate became rougher (Ra p = 0.041; Rq p = 0.014), as confirmed by SEM imaging. CONCLUSIONS: The acidic scenario tested in the present study changed the surface roughness of the resin composites but not their Vickers microhardness. Moreover, both resin composites seem suitable for use under acidic scenarios, although Paradigm MZ100 showed enhanced stability compared to Lava Ultimate. PMID- 26682955 TI - Prediction of survival and magnitude of reverse remodeling using the ST2-R2 score in heart failure: A multicenter study. AB - BACKGROUND: Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. METHODS: A total of 569 patients with baseline LVEF <40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and beta-blocker treatment. RESULTS: A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from +5.6% to +17.3%; p<0.001), percentage reduction in LV end-systolic volume index (from 6.1% to -32.1%; p<0.001) and in LV end-systolic diameter index (from -1.1% to 18.6%; p<0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (<9) as a reference, were 0.49 (p<0.001; score 9-11), 0.27 (p<0.001; score 12-14), and 0.17 (p<0.001; score 15-17). CONCLUSIONS: The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4years. PMID- 26682956 TI - Giant pulmonary trunk with Eisenmenger flow through patent ductus arteriosus. PMID- 26682957 TI - Tandem pulsed acousto-optics: obtaining the tagged light fraction from modulated non-ideal speckle patterns. AB - Recently we presented novel methods for acousto-optic (AO) imaging of biological tissues, taking (1) the mean square difference of speckle patterns (subtraction method) or (2) the contrast of the summation of speckle patterns (summation method) acquired from nanosecond pulses of coherent light, fired at different ultrasound phases. In this study we relate the two methods both analytically and experimentally. We experimentally show that these two methods are nearly identical provided that the maximum achievable speckle contrast is determined correctly. We show with simulations that after correction the outcome is independent of experimental detection parameters. This makes the AO methods in this study reliable, allowing quantifying speckle observations in terms of the ultrasonically tagged fractions of light. The use of tandem nanosecond pulses in one burst of ultrasound overcomes the challenge of tissue dynamics. PMID- 26682958 TI - Cannabis use is associated with 3years earlier onset of schizophrenia spectrum disorder in a naturalistic, multi-site sample (N=1119). AB - BACKGROUND: Patients with schizophrenia spectrum disorders and substance use may have an earlier onset of illness compared to those without substance use. Most previous studies have, however, too small samples to control for confounding variables and the effect of specific types of substances. The present study aimed to examine the relationship between substance use and age at onset, in addition to the influence of possible confounders and specific substances, in a large and heterogeneous multisite sample of patients with schizophrenia spectrum disorders. METHODS: The patients (N=1119) were recruited from catchment areas in Oslo, Stavanger and Bergen, Norway, diagnosed according to DSM-IV and screened for substance use history. Linear regression analysis was used to examine the relationship between substance use and age at onset of illness. RESULTS: Patients with substance use (n=627) had about 3years earlier age at onset (23.0years; SD 7.1) than the abstinent group (n=492; 25.9years; SD 9.7). Only cannabis use was statistically significantly related to earlier age at onset. Gender or family history of psychosis did not influence the results. CONCLUSION: Cannabis use is associated with 3years earlier onset of psychosis. PMID- 26682959 TI - CSII: Longer Catheter Usage Time, a Reasonable Goal. PMID- 26682960 TI - Telemedicine for Diabetes: Current and Future Trends. PMID- 26682961 TI - Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M). AB - OBJECTIVES: Tigecycline represents one of the last-line therapeutics to combat multidrug-resistant bacterial pathogens, including VRE and MRSA. The German National Reference Centre for Staphylococci and Enterococci has received 73 tigecycline-resistant Enterococcus faecium and Enterococcus faecalis isolates in recent years. The precise mechanism of how enterococci become resistant to tigecycline remains undetermined. This study documents an analysis of the role of efflux pumps in tigecycline resistance in clinical isolates of Enterococcus spp. METHODS: Various tigecycline MICs were found for the different isolates analysed. Tigecycline-resistant strains were analysed with respect to genome and transcriptome differences by means of WGS and RT-qPCR. Genes of interest were cloned and expressed in Listeria monocytogenes for verification of their functionality. RESULTS: Detailed comparative whole-genome analyses of three isogenic strains, showing different levels of tigecycline resistance, revealed the major facilitator superfamily (MFS) efflux pump TetL and the ribosomal protection protein TetM as possible drug resistance proteins. Subsequent RT-qPCR confirmed up-regulation of the respective genes. A correlation of gene copy number and level of MIC was inferred from further qPCR analyses. Expression of both tet(L) and tet(M) in L. monocytogenes unequivocally demonstrated the potential to increase tigecycline MICs upon acquisition of either locus. CONCLUSIONS: Our results indicate that increased expression of two tetracycline resistance determinants, a tet(L)-encoded MFS pump and a tet(M)-encoded ribosomal protection protein, is capable of conferring tigecycline resistance in enterococcal clinical isolates. PMID- 26682962 TI - Post-prandial lipid effects of raltegravir versus darunavir/ritonavir in HIV-1 infected adults commencing combination ART. PMID- 26682963 TI - Pentacyclic nitrofurans that rapidly kill nifurtimox-resistant trypanosomes. AB - OBJECTIVES: In response to reports of Trypanosoma brucei resistance to the nitroaromatic drug nifurtimox, we evaluated the potential of antituberculosis nitrofuran isoxazolines as inhibitors of trypanosome growth. METHODS: The susceptibility of T. brucei brucei was assessed in vitro. The lowest effective concentration to inhibit growth (EC90) against drug-susceptible and -resistant parasites, time-kill kinetics, reversibility of inhibition and propensity for P glycoprotein-mediated exclusion from the blood-brain barrier were determined. RESULTS: Nitrofuran isoxazolines were potent inhibitors of T. brucei brucei proliferation at nanomolar concentrations, with pentacyclic nitrofurans being 100 fold more potent than nifurtimox. Activity was sustained against nifurtimox resistant parasites, suggesting the possibility of a unique mechanism of activation and potential for use in the treatment of drug-resistant infections. Exposure of parasites to the maximum concentrations of Compound 15 achieved in vivo with oral dosing yielded >2 logs of irreversible killing in <4 h, indicating rapid trypanocidal activity. CONCLUSIONS: Pentacyclic nitrofuran isoxazolines warrant further development for the treatment of drug-susceptible and nifurtimox resistant trypanosome infections. PMID- 26682965 TI - Get Fit for Lung Transplant With Ambulatory Extracorporeal Membrane Oxygenation! PMID- 26682966 TI - Circumstances When Arterial Blood Gas Analysis Can Lead Us Astray. PMID- 26682964 TI - Traditional and non-traditional risk factors for incident peripheral arterial disease among patients with chronic kidney disease. AB - BACKGROUND: The risk of peripheral arterial disease (PAD) is higher in patients with chronic kidney disease (CKD) compared with those without. However, reasons for this increased risk are not fully understood. METHODS: We studied risk factors for incident PAD among 3169 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Patients with CKD aged 21-74 years were recruited between 2003 and 2008 and followed for a median of 6.3 years. Incident PAD was defined as a new onset ankle-brachial index (ABI) of <0.9 or confirmed clinical PAD. RESULTS: In a multivariate-adjusted model, older age, female sex, non-Hispanic Black, current smoking, diabetes, higher pulse pressure, lower high density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were significantly associated with the increased risk of incident PAD. After adjustment for these traditional risk factors as well as use of medications and CRIC Study clinic sites, the following baseline novel risk factors were significantly associated with risk of incident PAD [hazard ratio and 95% confidence interval (CI) for a one standard deviation (SD) higher level]: log[C-reactive protein (CRP)] (1.16, 1.06-1.25, P < 0.001), white blood cell count (1.09, 1.01-1.18, P = 0.03), fibrinogen (1.15, 1.06-1.26, P = 0.002), log(myeloperoxidase) (1.12, 1.03-1.23, P = 0.01), uric acid (0.88, 0.80-0.97, P = 0.01), glycated hemoglobin (1.16, 1.05-1.27, P = 0.003), log(homeostatic model assessment-insulin resistance) (1.21, 1.10-1.32, P < 0.001) and alkaline phosphatase (1.15, 1.07-1.24, P < 0.001). CONCLUSIONS: Among patients with CKD, inflammation, prothrombotic state, oxidative stress, glycated hemoglobin, insulin resistance and alkaline phosphatase are associated with an increased risk of PAD, independent of traditional risk factors. PMID- 26682967 TI - Waiting to Exhale: Optimizing Noninvasive Synchrony in COPD? PMID- 26682968 TI - Editor's Commentary. PMID- 26682970 TI - Gender differences in macroprolactinomas: a single centre experience. AB - Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29+/-10.39 years) presented at younger mean age than males (35.23+/-9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36+/-6863.01 ng/ml) than males (7927.07+/-16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49+/-1.48 cm) was smaller than males (3.93+/-1.53 cm) (P<0.001). In 88 treatment naive patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1-2 cm, 2.1-4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females. PMID- 26682969 TI - Crystal structures of MBP fusion proteins. AB - Although chaperone-assisted protein crystallization remains a comparatively rare undertaking, the number of crystal structures of polypeptides fused to maltose binding protein (MBP) that have been deposited in the Protein Data Bank (PDB) has grown dramatically during the past decade. Altogether, 102 fusion protein structures were detected by Basic Local Alignment Search Tool (BLAST) analysis. Collectively, these structures comprise a range of sizes, space groups, and resolutions that are typical of the PDB as a whole. While most of these MBP fusion proteins were equipped with short inter-domain linkers to increase their rigidity, fusion proteins with long linkers have also been crystallized. In some cases, surface entropy reduction mutations in MBP appear to have facilitated the formation of crystals. A comparison of the structures of fused and unfused proteins, where both are available, reveals that MBP-mediated structural distortions are very rare. PMID- 26682971 TI - The effect of a brief educational programme added to mental health treatment to improve patient activation: A randomized controlled trial in community mental health centres. AB - OBJECTIVE: While there is growing interest in improving patient activation in general medical health services, there are too few randomized controlled trials in mental health settings which show how improvement can be achieved. Using the Patient Activation Measure-13 (PAM-13), we aimed to assess the effect of pre treatment, peer co-led educational intervention on patient activation. Secondary outcomes included measures of patient satisfaction, well-being, mental health symptoms, motivation, and treatment participation. METHODS: Patients from two community mental health centres were randomized to a control group (CG, n=26) receiving treatment as usual, or an intervention group (IG, n=26) consisting of a four-hour group educational seminar (aiming to encourage patients to adopt an active role in their treatment) followed by treatment as usual. RESULTS: Only the IG improved on PAM-13, at one- and four-month follow-ups. The intervention had significant effects on patient satisfaction and treatment participation, compared to CG. CONCLUSION: Providing pre-treatment, peer co-led education improves patient activation in community mental health care settings. PRACTICE IMPLICATIONS: The use of peers as co-educators may contribute to a different mental health care delivery, ensuring patient activation and participation in treatment. Further studies should examine peers' needs for supervision, challenges for the services, long-term and cost-benefit effects. CLINICALTRIALS. GOV IDENTIFIER: NCT01601587. PMID- 26682972 TI - Kidney transplant patients' attitudes towards self-management support: A Q methodological study. AB - OBJECTIVE: Kidney transplant recipients face many self-management challenges. We aimed to identify profiles of attitudes towards self-management support (SMS) shortly after kidney transplantation. METHODS: Profiles were generated using Q methodology: In face-to-face interviews participants rank-ordered opinion statements on aspects of SMS according to agreement. Socio-demographic and medical characteristics were assessed using a questionnaire. By-person factor analysis was used to analyze the rankings and qualitative data was used to support choice of profiles. The resulting factors represent clusters of patients with similar attitudes towards SMS. RESULTS: Forty-three patients (mean age=56; 77% male) participated. Four profiles were identified: (A) transplant-focused and obedient; (B) holistic and collaborative; (C) life-focused and self-determined; and (D) was bipolar. The positive pole (D+) minimalizing and disengaged and the negative pole (D-) coping-focused and needy represent opposing viewpoints within the same profile. Socio-demographic and medical characteristics were not related to profile membership. DISCUSSION: Each profile represents a specific attitude on post-transplant life, responsibility for health and decision-making, SMS needs, and preferences for SMS. PRACTICAL IMPLICATIONS: Patients vary in their attitude, needs and preferences for SMS indicating the necessity of providing personalized support after kidney transplantation. Health professionals should explore patients' SMS needs and adapt support accordingly. PMID- 26682974 TI - Fetal HSCs versus EMP2s. PMID- 26682973 TI - The Origin of Tissue-Resident Macrophages: When an Erythro-myeloid Progenitor Is an Erythro-myeloid Progenitor. PMID- 26682975 TI - Germinal Centers: Gaining Strength from the Dark Side. AB - Germinal center B cells exist in two conditions, a dark zone state and a light zone state. Two studies in this issue (Dominguez-Sola et al., 2015; Sander et al., 2015) report that Foxo1 deficiency causes an almost complete loss of dark zone cells and an inability to undergo robust antibody affinity maturation. PMID- 26682976 TI - Live Long and Prosper for Antigen Cross-Presentation. AB - Even though proteolytic antigen fragments are displayed for cross-presentation, rapid proteolysis of endocytosed antigens inhibits this process. In this issue of Immunity, Alloatti et al. (2015) describe how maturing dendritic cells keep phagosomes and lysosomes apart to ensure extended antigen life that leads to prosperous cross-presentation. PMID- 26682977 TI - Front-Line Memory T Cells Think Outside the T-box... Mostly. AB - Tissue-resident memory T (Trm) cells patrol barrier tissues. In this issue of Immunity, Carbone and colleagues show that downregulation of T-box proteins Eomesodermin and T-bet is critical for their differentiation, but residual levels of T-bet are important for long-term Trm survival and function. PMID- 26682978 TI - The Good, the Bad, or the Pretty: IL-17 Builds Lymphoid Tissues in the Brain. AB - Lymph node development depends on well-orchestrated interactions between lymphoid tissue inducer cells and stromal cells. In this issue of Immunity, Pikor and colleagues (2015) find that signals from IL-17-producing T helper cells can alter the stromal microenvironment of the inflamed brain to generate a neo-lymphoid organ that drives further inflammation. PMID- 26682979 TI - Powerful Populations Respond to Viruses and Vaccines. AB - In this issue of Immunity, Andres-Terre et al. (2015) and Nakaya et al. (2015) perform multi-cohort meta-analyses of immune responses to viruses and vaccines. With increased statistical power and more diverse sampling populations, their findings promise to be more generally applicable and suggestive of novel mechanisms for regulating immunity. PMID- 26682980 TI - Small but Mighty: Selected Commensal Bacterial Species Determine the Effectiveness of Anti-cancer Immunotherapies. AB - Commensal microorganisms influence malignant progression by altering systemic inflammation. New data from two groups (Vetizou et al., 2015; Sivan et al., 2015) indicate that the abundance of specific commensal bacterial species enhances the anti-cancer activity of immune checkpoint inhibitors. PMID- 26682981 TI - Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. AB - The T helper 17 (Th17) cell pathway has been linked by genome-wide association studies to multiple autoimmune diseases. Identification of the genetic causes of primary immunodeficiency diseases revealed that Th17 cells are also critical in host immunity to mucocutaneous candida infections and Staphylococcus aureus. Therapeutic interventions with inhibitors of the different components of the pathway such as interleukin-12 (IL-12), IL-23, IL-17A, and IL-17RA have variably beneficial effects in psoriasis, Crohn's disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-infectious uveitis, and multiple sclerosis. Thus, whereas Th17 cells are protective against Candida albicans and to a lesser degree Staphylococcus aureus, they are pathogenic in many autoimmune diseases. Here, we compare and contrast the effects of human genetic mutations of and therapeutic interventions targeted at Th17 cell molecules. We discuss that although there are similarities when Th17 cell pathway molecules are modulated, each molecule has unique non-Th17 cell features that lead to different functional outcomes. PMID- 26682982 TI - Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. AB - The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 A that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates. PMID- 26682983 TI - Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens. AB - The initiation of cytotoxic immune responses by dendritic cells (DCs) requires the presentation of antigenic peptides derived from phagocytosed microbes and infected or dead cells to CD8(+) T cells, a process called cross-presentation. Antigen cross-presentation by non-activated DCs, however, is not sufficient for the effective induction of immune responses. Additionally, DCs need to be activated through innate receptors, like Toll-like receptors (TLRs). During DC maturation, cross-presentation efficiency is first upregulated and then turned off. Here we show that during this transient phase of enhanced cross presentation, phago-lysosome fusion was blocked by the topological re organization of lysosomes into perinuclear clusters. LPS-induced lysosomal clustering, inhibition of phago-lysosome fusion and enhanced cross-presentation, all required expression of the GTPase Rab34. We conclude that TLR4 engagement induces a Rab34-dependent re-organization of lysosomal distribution that delays antigen degradation to transiently enhance cross-presentation, thereby optimizing the priming of CD8(+) T cell responses against pathogens. PMID- 26682984 TI - T-box Transcription Factors Combine with the Cytokines TGF-beta and IL-15 to Control Tissue-Resident Memory T Cell Fate. AB - Tissue-resident memory T (Trm) cells contribute to local immune protection in non lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-beta cytokine signaling. TGF-beta signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor beta-chain (CD122) expression and thus IL 15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-beta and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival. PMID- 26682985 TI - Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF Dependent Control of Mycobacterium tuberculosis Infection. AB - The interleukin-1 receptor I (IL-1RI) is critical for host resistance to Mycobacterium tuberculosis (Mtb), yet the mechanisms of IL-1RI-mediated pathogen control remain unclear. Here, we show that without IL-1RI, Mtb-infected newly recruited Ly6G(hi) myeloid cells failed to upregulate tumor necrosis factor receptor I (TNF-RI) and to produce reactive oxygen species, resulting in compromised pathogen control. Furthermore, simultaneous ablation of IL-1RI and TNF-RI signaling on either stroma or hematopoietic cells led to early lethality, indicating non-redundant and synergistic roles of IL-1 and TNF in mediating macrophage-stroma cross-talk that was critical for optimal control of Mtb infection. Finally, we show that even in the presence of functional Mtb-specific adaptive immunity, the lack of IL-1alpha and not IL-1beta led to an exuberant intracellular pathogen replication and progressive non-resolving inflammation. Our study reveals functional interdependence between IL-1 and TNF in enabling Mtb control mechanisms that are critical for host survival. PMID- 26682986 TI - Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection. AB - Toll-like receptor 9 (TLR9), its adaptor MyD88, the downstream transcription factor interferon regulatory factor 7 (IRF7), and type I interferons (IFN-I) are all required for resistance to infection with ectromelia virus (ECTV). However, it is not known how or in which cells these effectors function to promote survival. Here, we showed that after infection with ECTV, the TLR9-MyD88-IRF7 pathway was necessary in CD11c(+) cells for the expression of proinflammatory cytokines and the recruitment of inflammatory monocytes (iMos) to the draining lymph node (dLN). In the dLN, the major producers of IFN-I were infected iMos, which used the DNA sensor-adaptor STING to activate IRF7 and nuclear factor kappaB (NF-kappaB) signaling to induce the expression of IFN-alpha and IFN-beta, respectively. Thus, in vivo, two pathways of DNA pathogen sensing act sequentially in two distinct cell types to orchestrate resistance to a viral disease. PMID- 26682987 TI - Integration of Th17- and Lymphotoxin-Derived Signals Initiates Meningeal-Resident Stromal Cell Remodeling to Propagate Neuroinflammation. AB - Tertiary lymphoid tissues (TLTs) have been observed in the meninges of multiple sclerosis (MS) patients, but the stromal cells and molecular signals that support TLTs remain unclear. Here, we show that T helper 17 (Th17) cells induced robust TLTs within the brain meninges that were associated with local demyelination during experimental autoimmune encephalitis (EAE). Th17-cell-induced TLTs were underpinned by a network of stromal cells producing extracellular matrix proteins and chemokines, enabling leukocytes to reside within, rather than simply transit through, the meninges. Within the CNS, interactions between lymphotoxin alphabeta (LTalphabeta) on Th17 cells and LTbetaR on meningeal radio-resistant cells were necessary for the propagation of de novo interleukin-17 responses, and activated T cells from MS patients expressed elevated levels of LTbetaR ligands. Therefore, input from both Th17 cells and the lymphotoxin pathway induce the formation of an immune-competent stromal cell niche in the meninges. PMID- 26682990 TI - Frequency of folate deficiency in multiple myeloma patients: a 10-year retrospective study. PMID- 26682988 TI - Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures. AB - Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza. PMID- 26682989 TI - Integrated, Multi-cohort Analysis Identifies Conserved Transcriptional Signatures across Multiple Respiratory Viruses. AB - Respiratory viral infections are a significant burden to healthcare worldwide. Many whole genome expression profiles have identified different respiratory viral infection signatures, but these have not translated to clinical practice. Here, we performed two integrated, multi-cohort analyses of publicly available transcriptional data of viral infections. First, we identified a common host signature across different respiratory viral infections that could distinguish (1) individuals with viral infections from healthy controls and from those with bacterial infections, and (2) symptomatic from asymptomatic subjects prior to symptom onset in challenge studies. Second, we identified an influenza-specific host response signature that (1) could distinguish influenza-infected samples from those with bacterial and other respiratory viral infections, (2) was a diagnostic and prognostic marker in influenza-pneumonia patients and influenza challenge studies, and (3) was predictive of response to influenza vaccine. Our results have applications in the diagnosis, prognosis, and identification of drug targets in viral infections. PMID- 26682991 TI - Endometrial Cancer Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression Increases with Body Mass Index and Is Associated with Pathologic Extent and Prognosis. AB - BACKGROUND: Obesity is a main risk factor for endometrial carcinoma (EC). Insulin like growth factor 1 receptor (IGF1R) expression may influence this association. METHODS: IGF1R IHC was performed on a tissue microarray with 894 EC and scored according to the percentage and intensity of staining to create immunoreactivity scores, which were dichotomized into low and high IGF1R expression groups. Logistic regression modeling assessed associations with body mass index (BMI), age, histology, pathologic extent of disease (pT), and lymph node metastasis (pN). Overall survival (OS) and disease-free survival (DFS) were compared between IGF1R expression groups using Kaplan-Meier curves and log-rank tests. RESULTS: The proportion of patients with high IGF1R expression increased as BMI (<30, 30 39, and 40+ kg/m(2)) increased (P = 0.002). The adjusted odds of having high IGF1R expression was 1.49 [95% confidence interval (CI), 1.05-2.10, P = 0.024] for patients with BMI 30 to 39 kg/m(2) compared with <30 kg/m(2) and 1.62 (95% CI, 1.13-2.33, P = 0.009) for patients with BMI 40+ kg/m(2) compared with <30 kg/m(2). High IGF1R expression was associated with pT and pN univariately and with pT after adjusting for BMI, pN, age, and histologic subtype. DFS and OS were better with high IGF1R expression, P = 0.020 and P = 0.002, respectively, but DFS was not significant after adjusting for pT, pN, and histologic subtype of the tumor. CONCLUSIONS: There is an association between BMI and EC IGF1R expression. Higher IGF1R expression is associated with lower pT and better DFS and OS. IMPACT: These findings suggest a link between IGF1R EC expression and obesity, as well as IGF1R expression and survival. PMID- 26682992 TI - Cortical interneuron dysfunction in epilepsy associated with autism spectrum disorders. AB - Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biologic mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic, and neurophysiologic levels in humans and in animal models. Scopus and PubMed searches were used to identify relevant literature. Clinical observations have prompted speculation about the interdependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability, the genetic basis of autism spectrum disorder (ASD) and epilepsy has remained largely elusive until the advent of next-generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes, any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes can be genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are among the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, gamma-aminobutyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurologic and neuropsychiatric manifestations are caused by an altered ratio of excitation to inhibition in the cortex. PMID- 26682993 TI - Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients. AB - BACKGROUND: Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse. OBJECTIVE: Objective of this study is to determine the differences in the demographic and genetic characteristics of patients with behavioral symptom at the onset of HD from those with motor symptoms. METHODS: A chart review of 92 patients with HD who had attended the neurology outpatient clinics of National Institute of Mental Health and Neurosciences, India was done. Demographic and genetic characteristics of HD patients with onset of the disease with initial behavioral symptoms (HD-iB) were compared with patients with onset of the disease with initial motor symptoms (HD-iM). RESULTS: The principal findings in our study were (i) higher proportion of patients with HD-iB had a positive family history of HD, (ii) maternal inheritance of HD was more frequent among those with HD-iB, and (iii) There is no significant difference between the CAG repeat length between HD-iB and HD-iM groups. CONCLUSION: Presence of family history of HD especially inheritance of HD from mother may be associated with behavioral symptoms at the onset of HD. CAG repeat length in patients with HD-iB does not differ from those with HD-iM. PMID- 26682994 TI - From the Editor-in-Chief's Desk. PMID- 26682995 TI - Hyperprolactinemia in Children and Adolescents with Use of Risperidone: Clinical and Molecular Genetics Aspects. AB - OBJECTIVE: In children and adolescents treated with risperidone, hyperprolactinemia is a frequent complication that may have clinical repercussions. Several genes have been associated with this occurrence. The aim of this study was to evaluate the frequency of hyperprolactinemia in children and adolescents treated with risperidone, and its associations with clinical and pharmacological data and certain polymorphisms of the following genes: Dopamine receptor D2 (DRD2), 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), and scavenger receptor class B, member 2 (SCARB2). METHODS: The study included patients using risperidone (8-20 years old) and healthy subjects not exposed to the medication. Psychopathological symptoms, doses, and duration of treatment with risperidone, sex, skin color, body mass index (BMI), use of other psychotropic drugs, and polymorphisms of DRD2, HTR2C, CYP2D6, LEP, LEPR, MC4R, and SCARB2 genes were evaluated. RESULTS: There were 120 patients and 197 individuals not exposed to risperidone who were evaluated. Among patients, hyperprolactinemia was found in 79 (65.8%) cases, with no differences regarding sex, skin color, or being in monotherapy with risperidone (26.7% of total patients) or not. The level of prolactin was not correlated, either in case or control groups, with chronological age, bone age, prescribed dose of risperidone, weight-adjusted dose of risperidone, or BMI (p > 0.05), but was negatively correlated with the treatment duration (r = -0.352, p = 0.001 among cases; and r = -0.324, p = 0.039 among controls). There were significant differences in use of risperidone between patients and healthy subjects without the medication in the frequency of the polymorphisms of the DRD2, HTR2C, and LEP genes. Considering both sexes together and also specifically among females, the occurrence of hyperprolactinemia was higher in the presence of the C allele of the rs6318 single nucleotide polymorphisms (SNP) of the HTR2C gene. CONCLUSIONS: This group of children and adolescents with or without isolated use of risperidone presented with a high frequency of hyperprolactinemia, although asymptomatic, and associated, when considering only females or both sexes together, with being a carrier of the C allele of the rs6318 SNP of the HTR2C gene. PMID- 26682996 TI - An Alternative Approach to Scoring the MTA-SNAP-IV to Guide Attention Deficit/Hyperactivity Disorder Medication Treatment Titration towards Symptom Remission: A Preliminary Consideration. AB - OBJECTIVE: The Multimodal Treatment Study for Attention-Deficit/Hyperactivity Disorder Swanson, Nolan, and Pelham, Version IV (MTA-SNAP-IV) is a common rating scale to measure attention-deficit/hyperactivity disorder (ADHD) symptoms during medication treatment. Relying on the traditional scoring approach for this instrument to identify symptom remission, however, may leave a child with significant residual symptoms. The objective of this study was to examine an alternative scoring approach for this instrument to identify the extent of residual symptoms for children completing ADHD medication treatment. METHODS: Parent and teacher ratings on the ADHD symptom component of the MTA-SNAP-IV were extracted from medical records of 80 children completing medication treatment at a specialty clinic in Canada. Data were scored in two ways. 1) Traditional scoring based on assigning a value ranging from 0 to 3 for response options: "Not at all," "Just a little," "Pretty much," or "Very much," for each symptom and then determining a mean across items, and 2) alternative scoring based on assigning values of 0, 0, 0.5, and 1 across the same response options and summing the total across items. Symptom remission based on the former is defined as a mean value <= 1, and for the latter it is defined as a summed value equal to 0. RESULTS: Children were significantly less likely to be classified as symptom remitted under the alternative scoring method based on parent, teacher, and combined parent-teacher ratings. Using the alternative scoring approach, residual symptoms were identified for 25%, 39%, and 70% of children classified as symptom remitted (under traditional scoring rules) by parents, teachers, and parents/teachers combined, respectively. CONCLUSIONS: Potential "residual" ADHD symptoms were identified in many children attaining symptom remission using the traditional scoring approach; however, further scrutiny of this alternative scoring approach is required. Although it may improve the ability to detect residual symptoms that could signal the need for further intervention to achieve symptom remission, it may increase the risk of over treatment. PMID- 26682997 TI - A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder. AB - OBJECTIVE: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Omega3), individual family psychoeducational psychotherapy (IF PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). METHODS: This study was a 12 week, randomized trial of Omega3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 * 2 design (Omega3 + PEP: n = 5; Omega3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7 14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Omega3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. RESULTS: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Omega3 on depression was medium (d = 0.48, KDRS). CONCLUSION: IF-PEP and Omega3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753. PMID- 26682998 TI - Biochemical and Psychological Effects of Omega-3/6 Supplements in Male Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Placebo Controlled, Clinical Trial. AB - BACKGROUND: An abnormality in long chain-polyunsaturated fatty acid (LC-PUFA) levels has been implicated in attention-deficit/hyperactivity disorder (ADHD). Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and, therefore, inconclusive results. METHODS: Seventy-six male adolescents (age 12-16 years, mean = 13.7) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a randomized, placebo-controlled, clinical trial. The primary outcome measure was change in the Conners' Teacher Rating Scales (CTRS) following 12 weeks of supplementation of LC-PUFA or placebo. At baseline, the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine. In the treatment group, supplementation enhanced eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total omega-3 fatty acid levels. RESULTS: No superiority of LC-PUFAs to placebo was observed on the primary outcome. Further, there were no reliable treatment effects on aggression, impulsivity, depression, and anxiety. CONCLUSIONS: Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD. PMID- 26683000 TI - Drug-Induced Psychosis Associated with Albendazole-Ivermectin Combination Therapy in a 10-Year-Old Child. PMID- 26682999 TI - Clinically Significant Symptom Reduction in Children with Attention Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study. AB - OBJECTIVE: The purpose of this study was to investigate the clinical effect and safety of a broad spectrum, 36 ingredient micronutrient (vitamins and minerals) in treating children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This open-label, on-off-on-off (reversal design) study followed 14 participants (8-12 years of age) with ADHD, diagnosed using standardized instruments, for 6 months with no dropouts. Following baseline assessment, including hematology and biochemistry screening, participants began an 8 week treatment phase with micronutrients titrated up to maximum dose (15 capsules/day). Treatment was withdrawn for 4 weeks, reinstated for a further 8 weeks, and then withdrawn for 4 weeks. Primary outcomes included the Conners' Parent Rating Scale, the Clinical Global Impressions Scale (CGI), and the Strengths and Difficulties Questionnaire - Parent version (SDQ). Secondary outcomes were mood and global functioning. RESULTS: Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post exposure of micronutrients (d = 1.2-2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as "much improved" or "very much improved" at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses. CONCLUSIONS: This study demonstrates the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD. Replications utilizing double blind placebo-controlled studies are warranted. Trial is registered with the Australia and New Zealand Clinical Trial Registry: ACTRN12612000645853. PMID- 26683002 TI - Chemo/Photoacoustic Dual Therapy with mRNA-Triggered DOX Release and Photoinduced Shockwave Based on a DNA-Gold Nanoplatform. AB - A multifunctional nanoparticle based on gold nanorod (GNR), utilizing mRNA triggered chemo-drug release and near-infrared photoacoustic effect, is developed for a combined chemo-photoacoustic therapy. The constructed nanoparticle (GNR DNA/FA:DOX) comprises three functional components: (i) GNR as the drug delivery platform and photoacoustic effect enhancer; (ii) toehold-possessed DNA dressed on the GNR to load doxorubicin (DOX) to implement a tumor cell specific chemotherapy; and (iii) folate acid (FA) modified on GNR to guide the nanoparticle to target tumor cells. The results show that, upon an effective and specific delivery of the nanoparticles to the tumor cells with overexpressed folate receptors, the cytotoxic DOX loaded on the GNR-DNA nanoplatform can be released through DNA displacement reaction in melanoma-associated antigen gene mRNA expressed cells. With 808 nm pulse laser irradiation, the photoacoustic effect of the GNR leads to a direct physical damage to the cells. The combined treatment of the two modalities can effectively destroy tumor cells and eradicate the tumors with two distinctively different and supplementing mechanisms. With the nanoparticle, photoacoustic imaging is successfully performed in situ to monitor the drug distribution and tumor morphology for therapeutical guidance. With further in-depth investigation, the proposed nanoparticle may provide an effective and safe alternative cancer treatment modality. PMID- 26683004 TI - Outcome of phacoemulsification following corneal and lens laceration in cats and dogs (2000-2010). AB - OBJECTIVE: To investigate the success rate of phacoemulsification following corneal and lens laceration in dogs and cats. PROCEDURE: Retrospective review of cats and dogs presenting with corneal and lens laceration and treated with phacoemulsification. RESULTS: The records of 33 patients (33 eyes: six feline, 27 canine) presenting to a private referral center were reviewed. Affected dogs were younger (median 18 months) than affected cats (median 30 months). The lacerations were caused by cat scratch trauma (9/33), thorn injury (6/33), and glass shards (1/33); the cause was unknown in 17/33 cases. All cats and 85.2% of all dogs were visual at the last examination. The median follow-up was 4 and 8 months for cats and dogs, respectively. In all canine cases that developed vision loss, this occurred within the first 14 weeks postoperatively. The ultimate cause for vision loss in dogs was secondary glaucoma (4/4) and retinal detachment (1/4). CONCLUSION: Cats have an excellent outcome and dogs a very good outcome following surgery for corneal and lens laceration. The cause of the trauma, the size of the lesion, the time interval between the ocular trauma and surgery, and the type of surgery were not found to have an influence on the outcome of patients in this study. We postulate that vision loss might develop more often in cases with complications associated with the initial corneal laceration wound. PMID- 26683003 TI - Plasma HMGB-1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses. AB - BACKGROUND: Acute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis. HYPOTHESES: Increased plasma concentrations of the biomarkers HMGB-1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA. ANIMALS: Thirty horses with gastrointestinal disease, 22 healthy horses. METHODS: Prospective study. Plasma samples taken on admission were used for measurement of HMGB-1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed. RESULTS: Plasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P <= .001). HMGB-1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5-fold and 5.4-fold increases, respectively, for HMGB-1 (P < .05) and 4.8-fold and 5.6-fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB-1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers. CONCLUSIONS AND CLINICAL IMPORTANCE: High mobility group box-1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses. PMID- 26683005 TI - Restoring Africa's health systems after Ebola. PMID- 26683006 TI - Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants. AB - Betalains are tyrosine-derived red-violet and yellow pigments, found in plants only of the Caryophyllales order. Although much progress has been made in recent years in the understanding of the betalain biosynthetic process, many questions remain open with regards to several of the proposed steps in the pathway. Most conspicuous by its absence is the characterization of the first committed step in the pathway, namely the 3-hydroxylation of tyrosine to form l-3,4 dihydroxyphenylalanine (l-DOPA). We used transcriptome analysis of the betalain producing plants red beet (Beta vulgaris) and four o'clocks (Mirabilis jalapa) to identify a novel, betalain-related cytochrome P450-type gene, CYP76AD6, and carried out gene silencing and recombinant expression assays in Nicotiana benthamiana and yeast cells to examine its functionality. l-DOPA formation in red beet was found to be redundantly catalyzed by CYP76AD6 together with a known betalain-related enzyme, CYP76AD1, which was previously thought to only catalyze a succeeding step in the pathway. While CYP76AD1 catalyzes both l-DOPA formation and its subsequent conversion to cyclo-DOPA, CYP76AD6 uniquely exhibits only tyrosine hydroxylase activity. The new findings enabled us to metabolically engineer entirely red-pigmented tobacco plants through heterologous expression of three genes taking part in the fully decoded betalain biosynthetic pathway. PMID- 26683007 TI - Assessment of bioabsorbable hydroxyapatite for secondary bone grafting in unilateral alveolar cleft. AB - AIM: The aim of this study was to evaluate the utility and efficacy of bioabsorbable hydroxyapatite and collagen complex for secondary bone graft in unilateral alveolar cleft. PATIENTS AND METHODS: From August 2013 to January 2014, 15 patients with unilateral cleft lip and alveolar cleft were enrolled and randomly assigned to two blinded groups. In group I, a cancellous iliac bone graft was placed at the alveolar cleft. In group II, 0.5 ml of HA/Col was placed at the alveolar cleft, and the cancellous iliac bone was positioned in the remaining space. All patients underwent bone grafting with particulate cancellous bone and marrow taken from the anterior iliac crest. RESULTS: No complications were observed in any patient. The groups did not differ in age, cleft volume, or surgical duration. Intraoperative blood loss and patient-controlled intravenous analgesia (PCA) use were significantly lower in group II (p < 0.05) in comparison to group I. The 1-month volume was 0.895 ml in group I and 0.482 ml in group II (p < 0.05). When the 1-month volume in group II was adjusted for 0.5-ml volume of HA/Col, there was no significant difference in the 1-month volumes (p = 0.32). The 6- and 12-month volumes did not differ significantly between the groups (p = 0.768 and p = 0.165, respectively). CONCLUSION: The autogenous bone was gradually absorbed, while the HA/Col was absorbed and replaced by the autogenous bone. Thus, HA/Col can be used as an iliac graft in alveolar bone graft procedures to reduce the amount of autogenous bone required from the crest, patient stress, and morbidity. PMID- 26683008 TI - Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve. AB - Several techniques have been described for smile restoration after facial nerve paralysis. When a nerve other than the contralateral facial nerve is used to restore the smile, some controversy appears because of the nonphysiological mechanism of smile recovering. Different authors have reported natural results with the masseter nerve. The physiological pathways which determine whether this is achieved continue to remain unclear. Using functional magnetic resonance imaging, brain activation pattern measuring blood-oxygen-level-dependent (BOLD) signal during smiling and jaw clenching was recorded in a group of 24 healthy subjects (11 females). Effective connectivity of premotor regions was also compared in both tasks. The brain activation pattern was similar for smile and jaw-clenching tasks. Smile activations showed topographic overlap though more extended for smile than clenching. Gender comparisons during facial movements, according to kinematics and BOLD signal, did not reveal significant differences. Effective connectivity results of psychophysiological interaction (PPI) from the same seeds located in bilateral facial premotor regions showed significant task and gender differences (p < 0.001). The hypothesis of brain plasticity between the facial nerve and masseter nerve areas is supported by the broad cortical overlap in the representation of facial and masseter muscles. PMID- 26683021 TI - Adiponectin: A biomarker for chronic hepatitis C? AB - Adiponectin, a hormone primarily synthesized and secreted by adipose tissue, plays a pivotal role in lipid metabolism. Chronic hepatitis C (CHC) infection is characterized by disordered lipid metabolism, which may potentially evolve into steatosis over a period of time. A growing body of evidence appears to link decreased adiponectin plasma levels with severe CHC-related steatosis, which suggests a potential role of this adipokine as a diagnostic and therapeutic target for clinical application. In this review, we have attempted to summarize the current status of adiponectin research in the context of CHC, concentrating predominantly on its roles in CHC, and its potential relevance as a biomarker for CHC. PMID- 26683022 TI - A Comparative Study of Tests for Homogeneity of Variances with Application to DNA Methylation Data. AB - Variable DNA methylation has been associated with cancers and complex diseases. Researchers have identified many DNA methylation markers that have different mean methylation levels between diseased subjects and normal subjects. Recently, researchers found that DNA methylation markers with different variabilities between subject groups could also have biological meaning. In this article, we aimed to help researchers choose the right test of equal variance in DNA methylation data analysis. We performed systematic simulation studies and a real data analysis to compare the performances of 7 equal-variance tests, including 2 tests recently proposed in the DNA methylation analysis literature. Our results showed that the Brown-Forsythe test and trimmed-mean-based Levene's test had good performance in testing for equality of variance in our simulation studies and real data analyses. Our results also showed that outlier profiles could be biologically very important. PMID- 26683023 TI - Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma, including metabolite concentrations at steady state. AB - A novel, rapid and sensitive liquid chromatography tandem-mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi-quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi-quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5-100 MUg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26683024 TI - Comparison of Genetic Variants in Cancer-Related Genes between Chinese Hui and Han Populations. AB - BACKGROUND: The Chinese Hui population, as the second largest minority ethnic group in China, may have a different genetic background from Han people because of its unique demographic history. In this study, we aimed to identify genetic differences between Han and Hui Chinese from the Ningxia region of China by comparing eighteen single nucleotide polymorphisms in cancer-related genes. METHODS: DNA samples were collected from 99 Hui and 145 Han people from the Ningxia Hui Autonomous Region in China, and SNPs were detected using an improved multiplex ligase detection reaction method. Genotyping data from six 1000 Genomes Project population samples (99 Utah residents with northern and western European ancestry (CEU), 107 Toscani in Italy (TSI), 108 Yoruba in Ibadan (YRI), 61 of African ancestry in the southwestern US (ASW), 103 Han Chinese in Beijing (CHB), and 104 Japanese in Tokyo (JPT)) were also included in this study. Differences in the distribution of alleles among the populations were assessed using chi2 tests, and FST was used to measure the degree of population differentiation. RESULTS: We found that the genetic diversity of many SNPs in cancer-related genes in the Hui Chinese in Ningxia was different from that in the Han Chinese in Ningxia. For example, the allele frequencies of four SNPs (rs13361707, rs2274223, rs465498, and rs753955) showed different genetic distributions (p<0.05) between Chinese Ningxia Han and Chinese Ningxia Hui. Five SNPs (rs730506, rs13361707, rs2274223, rs465498 and rs753955) had different FST values (FST>0.000) between the Hui and Han populations. CONCLUSIONS: These results suggest that some SNPs associated with cancer-related genes vary among different Chinese ethnic groups. We suggest that population differences should be carefully considered in evaluating cancer risk and prognosis as well as the efficacy of cancer therapy. PMID- 26683025 TI - Modeling the Lymphatics. PMID- 26683026 TI - Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes. AB - BACKGROUND: Lymph nodes (LNs) are positioned strategically throughout the body as critical mediators of lymph filtration and immune response. Lymph carries cytokines, antigens, and cells to the downstream LNs, and their effective delivery to the correct location within the LN directly impacts the quality and quantity of immune response. Despite the importance of this system, the flow patterns in LN have never been quantified, in part because experimental characterization is so difficult. METHODS AND RESULTS: To achieve a more quantitative knowledge of LN flow, a computational flow model has been developed based on the mouse popliteal LN, allowing for a parameter sensitivity analysis to identify the important system characteristics. This model suggests that about 90% of the lymph takes a peripheral path via the subcapsular and medullary sinuses, while fluid perfusing deeper into the paracortex is sequestered by parenchymal blood vessels. Fluid absorption by these blood vessels under baseline conditions was driven mainly by oncotic pressure differences between lymph and blood, although the magnitude of fluid transfer is highly dependent on blood vessel surface area. We also predict that the hydraulic conductivity of the medulla, a parameter that has never been experimentally measured, should be at least three orders of magnitude larger than that of the paracortex to ensure physiologic pressures across the node. CONCLUSIONS: These results suggest that structural changes in the LN microenvironment, as well as changes in inflow/outflow conditions, dramatically alter the distribution of lymph, cytokines, antigens, and cells within the LN, with great potential for modulating immune response. PMID- 26683029 TI - Genome-Wide Dynamic Profiling of Histone Methylation during Nuclear Transfer Mediated Porcine Somatic Cell Reprogramming. AB - The low full-term developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos is mainly attributed to imperfect epigenetic reprogramming in the early embryos. However, dynamic expression patterns of histone methylation involved in epigenetic reprogramming progression during porcine SCNT embryo early development remain to be unknown. In this study, we characterized and compared the expression patterns of multiple histone methylation markers including transcriptionally repressive (H3K9me2, H3K9me3, H3K27me2, H3K27me3, H4K20me2 and H4K20me3) and active modifications (H3K4me2, H3K4me3, H3K36me2, H3K36me3, H3K79me2 and H3K79me3) in SCNT early embryos from different developmental stages with that from in vitro fertilization (IVF) counterparts. We found that the expression level of H3K9me2, H3K9me3 and H4K20me3 of SCNT embryos from 1-cell to 4-cell stages was significantly higher than that in the IVF embryos. We also detected a symmetric distribution pattern of H3K9me2 between inner cell mass (ICM) and trophectoderm (TE) in SCNT blastocysts. The expression level of H3K9me2 in both lineages from SCNT expanded blastocyst onwards was significantly higher than that in IVF counterparts. The expression level of H4K20me2 was significantly lower in SCNT embryos from morula to blastocyst stage compared with IVF embryos. However, no aberrant dynamic reprogramming of H3K27me2/3 occurred during early developmental stages of SCNT embryos. The expression of H3K4me3 was higher in SCNT embryos at 4-cell stage than that of IVF embryos. H3K4me2 expression in SCNT embryos from 8-cell stage to blastocyst stage was lower than that in the IVF embryos. Dynamic patterns of other active histone methylation markers were similar between SCNT and IVF embryos. Taken together, histone methylation exhibited developmentally stage specific abnormal expression patterns in porcine SCNT early embryos. PMID- 26683030 TI - Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice. AB - Male and female C57BL/6J mice were administered diquat dibromide (DQ?Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc. PMID- 26683031 TI - Weight Loss and Decrease of Body Mass Index during Allogeneic Stem Cell Transplantation Are Common Events with Limited Clinical Impact. AB - PURPOSE: Weight loss in cancer patients has been attributed with significant morbidity and mortality. During allogeneic stem cell transplantation (SCT), oral nutrition is often hampered and hence total parenteral nutrition (TPN) is necessary. We therefore investigated the course of weight during stem cell transplantation and the clinical consequences of weight change. METHODS: 180 consecutive patients who received allogeneic SCT between January 2010 and December 2011 at our center were analyzed for weight loss, laboratory and clinical parameters. RESULTS: During SCT, a median decrease of 6.6% of body mass index (BMI) was observed for the whole population (from 25.3 at admission to 23.6 at discharge), and a 1.6fold increase of malnutrition despite use of TPN (28.3% to 45.0%). 55.6% of patients experienced a significant weight loss of >=5% with a median decrease of 9.2% in BMI. Serum levels of albumin, total protein and cholesterol rapidly decreased during conditioning therapy. After a median of 2.4 years, the median BMI was still only 23.4 (not different from discharge). However, we did not observe a meaningful difference in side effects and survival between patients that did or did not lose weight. CONCLUSION: Weight loss is commonly observed during allogeneic SCT despite TPN, but the clinical consequences thereof seem limited: we observed no significant impact on patients with a decrease >= 5% in BMI on transplant outcome, side effects or survival. PMID- 26683033 TI - Tiotropium/Olodaterol: A Review in COPD. AB - Tiotropium/olodaterol (StioltoTM Respimat(r), SpioltoTM Respimat(r)) is a fixed dose combination of the long-acting antimuscarinic agent tiotropium bromide (hereafter referred to as tiotropium) and the long-acting beta2-adrenoreceptor agonist olodaterol delivered via the Respimat(r) Soft MistTM inhaler. It is indicated for the maintenance treatment of airflow obstruction in adults with COPD. Several randomized, phase III studies of 6-52 weeks' duration evaluated the efficacy of once-daily tiotropium/olodaterol in patients with GOLD stage 2-3 or 2 4 COPD. Tiotropium/olodaterol maintenance therapy improved lung function to a greater extent than the individual components or placebo and provided clinically meaningful improvements in health-related quality of life and dyspnoea in 12- and 52-week studies. Tiotropium/olodaterol consistently improved 24-h lung function in 6-week studies, providing greater benefits than the monotherapies, placebo or twice-daily fixed-dose fluticasone propionate/salmeterol. Inspiratory capacity and exercise endurance were also improved with tiotropium/olodaterol following 6 or 12 weeks' treatment. The tolerability profile of tiotropium/olodaterol in the phase III studies was generally similar to that of the component monotherapies. The most common adverse events and serious adverse events during 52 weeks' therapy were respiratory in nature, with COPD exacerbation, unsurprisingly, reported most frequently with tiotropium/olodaterol and component monotherapies. Although additional data assessing the effect of tiotropium/olodaterol on exacerbations and comparative studies with other recommended therapies are needed to definitively position tiotropium/olodaterol, current evidence indicates that tiotropium/olodaterol is a useful treatment option for patients with COPD. PMID- 26683032 TI - Individual and Partner-Level Factors Associated with Condom Non-Use Among African American STI Clinic Attendees in the Deep South: An Event-Level Analysis. AB - The US HIV/AIDS epidemic is concentrated in the Deep South, yet factors contributing to HIV transmission are not fully understood. We examined relationships between substance use, sexual partnership characteristics, and condom non-use in an African American sample of STI clinic attendees in Jackson, Mississippi. We assessed condom non-use at last intercourse with up to three recent sexual partners reported by participants between January and June 2011. Participant- and partner-level correlates of condom non-use were examined using generalized estimating equations. The 1295 participants reported 2880 intercourse events, of which 1490 (51.7 %) involved condom non-use. Older age, lower educational attainment, reporting financial or material dependence on a sex partner, sex with a primary partner, and higher frequency of sex were associated with increased odds of condomless sex. HIV prevention efforts in the South should address underlying socioeconomic disparities and structural determinants that result in partner dependency and sexual risk behavior. PMID- 26683034 TI - Primary liver cancer deaths and related years of life lost attributable to hepatitis B and C viruses in India. AB - BACKGROUND AND AIMS: More than 25,000 people die of liver cancer annually in India. There is little information about the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to these deaths. We conducted a systematic review of published studies on HBV or HCV infection and liver cancer in India and estimated the population attributable fraction (PAF) of liver cancer deaths caused by these infections and the corresponding annual number of deaths and years of life lost (YLL) in the country. METHODS: We searched the PubMed and Scopus databases, as well as the reference list of relevant articles in the systematic review. For calculation of the number of liver cancer deaths attributable to HBV and HCV, we used two sources of outcome data and two relative risks for the association between HCV and liver cancer. RESULTS: The PAF was 67% for HBV, 17-19% for HCV, and 71-72% for HBV and/or HCV. The annual attributable number of liver cancer deaths was approximately 17,000 for HBV; 4500 for HCV; and 18,500 for HBV and/or HCV, corresponding to approximately 297,000, 75,000, and 315,000 YLL, respectively. There was little difference in these numbers using the two sources of outcome data or the two risk estimates for HCV. CONCLUSIONS: Our findings underscore the importance of primary prevention of HBV and HCV by appropriate measures, including vaccination (HBV only), prevention of transfusion related infections, and increased awareness of the routes of transmission and long-term health outcomes. PMID- 26683035 TI - Reply to the Letter to the Editor: Surgical Technique: Tscherne-Johnson Extensile Approach for Tibial Plateau Fractures. PMID- 26683037 TI - Introduction to Special Issue on Age, Hearing, and Speech Comprehension. PMID- 26683036 TI - Universal Health Insurance Coverage in Massachusetts Did Not Change the Trajectory of Arthroplasty Use or Costs. AB - BACKGROUND: The state of Massachusetts enacted universal health insurance in 2006. However it is unknown whether the increased access to care resulted in changes to surgical use or costs. QUESTIONS/PURPOSES: We asked the following related research questions: compared with the United States as a whole, how did the (1) number of cases (as a percentage of the overall population, to account for changes in the overall population during the time surveyed), (2) payer mix, and (3) inpatient costs for arthroplasty change in Massachusetts after introduction of health insurance reform? METHODS: We analyzed the use and cost of primary THAs and TKAs in Massachusetts using the State Inpatient Database (SID) between 2002 and 2011 compared with the Nationwide Inpatient Sample (NIS) during the same years. The SID captures 100% of inpatient procedures in Massachusetts, while the NIS is a nationally representative database of inpatient procedures for the United States. The SID and NIS are publicly available data sources from the Agency for Healthcare Research and Quality, and include information regarding procedure volumes, payer mixes, and costs. Inpatient costs were defined similarly in both databases by using hospital charges and an average cost-to-charge ratio that is unique for each hospital. The incidence of arthroplasties was calculated by dividing the procedure volume by the relevant population (either for Massachusetts or the entire country) based on public data from the United States Census bureau. RESULTS: The incidence of THAs and TKAs performed in Massachusetts increased steadily throughout the study period, and paralleled a similar increase in the United States as a whole. In Massachusetts, the incidence of THAs increased by 59% between 2002 and 2011, and the incidence of TKAs likewise increased by 80%. The trends for the incidence in total joint arthroplasties were similar to those for Massachusetts for the United States as a whole. The period of health insurance reform in Massachusetts was associated with a greater proportion of patients covered by Medicaid, Commonwealth Care, or Health Safety Net for THAs and TKAs. By 2011, universal health insurance in Massachusetts covered 2.45% of primary THAs and 2.77% of primary TKAs. Coverage for Medicaid in Massachusetts increased from 3.23% and 3.04% of THAs and TKAs in 2002 to 4.06% and 4.34% respectively in 2011. On average, Medicaid coverage was greater for TKAs in Massachusetts than across the United States during the study period. The introduction of health insurance reform had a minimal effect on the cost of total joint arthroplasties in Massachusetts. Although the costs of total joint arthroplasties in the United States were higher than those in Massachusetts, this difference narrowed substantially from 2002 to 2011, with the Massachusetts cost trending upward and the overall United States cost trending downward. CONCLUSIONS: Despite extending insurance coverage to the entire state of Massachusetts, there was little change in actual utilization trends for joint replacement. CLINICAL RELEVANCE: The enactment of universal health insurance coverage in Massachusetts appears to have been a nonevent insofar as the use and cost of total hip and knee surgeries is concerned in the state. Factors other than health insurance reform appear to be driving the growth in demand for arthroplasties in Massachusetts and are likely to do so as well in the United States under the Affordable Care Act of 2010. PMID- 26683038 TI - Constraints on Sensitivity to Auditory Modulation in the Perceptual Organization of Speech. AB - BACKGROUND/STUDY CONTEXT: The perception of speech requires the integration of sensory details from a rapidly fading trace of a time-varying spectrum. This effortful cognitive function has been difficult to assess. New tests measuring intelligibility of sine-wave replicas of speech provided an assay of this critical function in normal-hearing young adults. METHODS: Four time-varying sinusoids replicated the frequency and amplitude variation of the natural resonances of spoken sentences. The temporal tolerance of perceptual integration of speech was measured by determining the effect on intelligibility of desynchronizing a single sine-wave component in each sentence. This method was applied in tests in which the sentences were temporally compressed or expanded over a 40% range. RESULTS: Desynchrony was harmful to perceptual integration over a narrow temporal range, indicating that modulation sensitivity is keyed to a rate of 20 Hz. No effect of variation in speech rate was observed on the intelligibility measure, whether rate was accelerated or decelerated relative to the natural rate. CONCLUSION: Performance measures of desynchrony tolerance did not vary when speech rate was accelerated or decelerated, revealing constraints on integration that are arguably primitive, sensory, auditory, and fixed. Because these are not adaptable, they limit the potential for perceptual learning in this aspect of perceptual organization. Implications for describing the elderly listener are noted. PMID- 26683039 TI - Effects of Vocal Emotion on Memory in Younger and Older Adults. AB - BACKGROUND/STUDY CONTEXT: Emotional content can enhance memory for visual stimuli, and older adults often perform better if stimuli portray positive emotion. Vocal emotion can enhance the accuracy of word repetition in noise when vocal prosody portrays attention-capturing emotions such as fear and pleasant surprise. In the present study, the authors examined the effect of vocal emotion on the accuracy of repetition and recall in younger and older adults when words are presented in quiet or in a background of competing babble. METHODS: Younger and older adults (Mage = 20 and 72 years, respectively) participated. Lists of 100 items (carrier phrase plus target word) were presented in recall sets of increasing size. Word repetition accuracy was tested after each item and recall after each trial in each set size. In Experiment 1, one list spoken in a neutral voice and another with emotion (fear, pleasant surprise, sad, neutral) were presented in quiet (n = 24 per group). In Experiment 2, participants (n = 12 per group) were presented the emotional list in noise. RESULTS: In quiet, word repetition accuracy was near perfect for both groups and did not vary systematically with set size for the list spoken in a neutral voice; however, for the emotional list, repetition was less accurate, especially for the older group. Recall in quiet was higher for younger than older adults; collapsed over groups, recall was higher for the neutral than for the emotional list and it decreased with increasing set size. In noise, emotion-specific effects emerged; word repetition for the older group and word recall for both groups (more for younger than older) was best for fear or pleasant surprise and worst for sad. CONCLUSION: In quiet, vocal emotion reduced the word repetition accuracy of the older group and recall accuracy for both groups. In noise, there were emotion-specific effects on the repetition accuracy of older adults and the recall accuracy of both groups. Both groups, but especially the younger group, performed better for items portraying fear or pleasant surprise and worse for items portraying sadness or neutral emotion. The emotion-specific effects on word repetition cascade to recall, especially in older listeners. PMID- 26683040 TI - How Spoken Language Comprehension is Achieved by Older Listeners in Difficult Listening Situations. AB - BACKGROUND/STUDY CONTEXT: Comprehending spoken discourse in noisy situations is likely to be more challenging to older adults than to younger adults due to potential declines in the auditory, cognitive, or linguistic processes supporting speech comprehension. These challenges might force older listeners to reorganize the ways in which they perceive and process speech, thereby altering the balance between the contributions of bottom-up versus top-down processes to speech comprehension. METHODS: The authors review studies that investigated the effect of age on listeners' ability to follow and comprehend lectures (monologues), and two-talker conversations (dialogues), and the extent to which individual differences in lexical knowledge and reading comprehension skill relate to individual differences in speech comprehension. Comprehension was evaluated after each lecture or conversation by asking listeners to answer multiple-choice questions regarding its content. RESULTS: Once individual differences in speech recognition for words presented in babble were compensated for, age differences in speech comprehension were minimized if not eliminated. However, younger listeners benefited more from spatial separation than did older listeners. Vocabulary knowledge predicted the comprehension scores of both younger and older listeners when listening was difficult, but not when it was easy. However, the contribution of reading comprehension to listening comprehension appeared to be independent of listening difficulty in younger adults but not in older adults. CONCLUSION: The evidence suggests (1) that most of the difficulties experienced by older adults are due to age-related auditory declines, and (2) that these declines, along with listening difficulty, modulate the degree to which selective linguistic and cognitive abilities are engaged to support listening comprehension in difficult listening situations. When older listeners experience speech recognition difficulties, their attentional resources are more likely to be deployed to facilitate lexical access, making it difficult for them to fully engage higher-order cognitive abilities in support of listening comprehension. PMID- 26683041 TI - Task-Related Vigilance During Word Recognition in Noise for Older Adults with Hearing Loss. AB - BACKGROUND/STUDY CONTEXT: Vigilance refers to the ability to sustain and adapt attentional focus in response to changing task demands. For older adults with hearing loss, vigilant listening may be particularly effortful and variable across individuals. This study examined the extent to which neural responses to sudden, unexpected changes in task structure (e.g., from rest to word recognition epochs) were related to pupillometry measures of listening effort. METHODS: Individual differences in the task-evoked pupil response during word recognition were used to predict functional magnetic resonance imaging (MRI) estimates of neural responses to salient transitions between quiet rest, noisy rest, and word recognition in unintelligible, fluctuating background noise. Participants included 29 older adults (M = 70.2 years old) with hearing loss (pure tone average across all frequencies = 36.1 dB HL [hearing level], SD = 6.7). RESULTS: Individuals with a greater average pupil response exhibited a more vigilant pattern of responding on a standardized continuous performance test (response time variability across varying interstimulus intervals r(27) = .38, p = .04). Across participants there was widespread engagement of attention- and sensory related cortices in response to transitions between blocks of rest and word recognition conditions. Individuals who exhibited larger task-evoked pupil dilation also showed even greater activity in the right primary auditory cortex in response to changes in task structure. CONCLUSION: Pupillometric estimates of word recognition effort predicted variation in activity within cortical regions that were responsive to salient changes in the environment for older adults with hearing loss. The results of the current study suggest that vigilant attention is increased amongst older adults who exert greater listening effort. PMID- 26683043 TI - Age Differences in Language Segmentation. AB - Reading bears the evolutionary footprint of spoken communication. Prosodic contour in speech helps listeners parse sentences and establish semantic focus. Readers' regulation of input mirrors the segmentation patterns of prosody, such that reading times are longer for words at the ends of syntactic constituents. As reflected in these "micropauses," older readers are often found to segment text into smaller chunks. The mechanisms underlying these micropauses are unclear, with some arguing that they derive from the mental simulation of prosodic contour and others arguing they reflect higher-level language comprehension mechanisms (e.g., conceptual integration, consolidation with existing knowledge, ambiguity resolution) that are common across modality and support the consolidation of the memory representation. The authors review evidence based on reading time and comprehension performance to suggest that (a) age differences in segmentation derive both from age-related declines in working memory, as well as from crystallized ability and knowledge, which have the potential to grow in adulthood, and that (b) shifts in segmentation patterns may be a pathway through which language comprehension is preserved in late life. PMID- 26683042 TI - Cingulo-Opercular Function During Word Recognition in Noise for Older Adults with Hearing Loss. AB - BACKGROUND/STUDY CONTEXT: Adaptive control, reflected by elevated activity in cingulo-opercular brain regions, optimizes performance in challenging tasks by monitoring outcomes and adjusting behavior. For example, cingulo-opercular function benefits trial-level word recognition in noise for normal-hearing adults. Because auditory system deficits may limit the communicative benefit from adaptive control, we examined the extent to which cingulo-opercular engagement supports word recognition in noise for older adults with hearing loss (HL). METHODS: Participants were selected to form groups with Less HL (n = 12; mean pure tone threshold, pure tone average [PTA] = 19.2 +/- 4.8 dB HL [hearing level]) and More HL (n = 12; PTA = 38.4 +/- 4.5 dB HL, 0.25-8 kHz, both ears). A word recognition task was performed with words presented in multitalker babble at +3 or +10 dB signal-to-noise ratios (SNRs) during a sparse acquisition fMRI experiment. The participants were middle-aged and older (ages: 64.1 +/- 8.4 years) English speakers with no history of neurological or psychiatric diagnoses. RESULTS: Elevated cingulo-opercular activity occurred with increased likelihood of correct word recognition on the next trial (t(23) = 3.28, p = .003), and this association did not differ between hearing loss groups. During trials with word recognition errors, the More HL group exhibited higher blood oxygen level dependent (BOLD) contrast in occipital and parietal regions compared with the Less HL group. Across listeners, more pronounced cingulo-opercular activity during recognition errors was associated with better overall word recognition performance. CONCLUSION: The trial-level word recognition benefit from cingulo opercular activity was equivalent for both hearing loss groups. When speech audibility and performance levels are similar for older adults with mild to moderate hearing loss, cingulo-opercular adaptive control contributes to word recognition in noise. PMID- 26683044 TI - Effects of Age, Acoustic Challenge, and Verbal Working Memory on Recall of Narrative Speech. AB - BACKGROUND/STUDY CONTEXT: A common goal during speech comprehension is to remember what we have heard. Encoding speech into long-term memory frequently requires processes such as verbal working memory that may also be involved in processing degraded speech. Here the authors tested whether young and older adult listeners' memory for short stories was worse when the stories were acoustically degraded, or whether the additional contextual support provided by a narrative would protect against these effects. METHODS: The authors tested 30 young adults (aged 18-28 years) and 30 older adults (aged 65-79 years) with good self-reported hearing. Participants heard short stories that were presented as normal (unprocessed) speech or acoustically degraded using a noise vocoding algorithm with 24 or 16 channels. The degraded stories were still fully intelligible. Following each story, participants were asked to repeat the story in as much detail as possible. Recall was scored using a modified idea unit scoring approach, which included separately scoring hierarchical levels of narrative detail. RESULTS: Memory for acoustically degraded stories was significantly worse than for normal stories at some levels of narrative detail. Older adults' memory for the stories was significantly worse overall, but there was no interaction between age and acoustic clarity or level of narrative detail. Verbal working memory (assessed by reading span) significantly correlated with recall accuracy for both young and older adults, whereas hearing ability (better ear pure tone average) did not. CONCLUSION: The present findings are consistent with a framework in which the additional cognitive demands caused by a degraded acoustic signal use resources that would otherwise be available for memory encoding for both young and older adults. Verbal working memory is a likely candidate for supporting both of these processes. PMID- 26683045 TI - Social Coordination in Older Adulthood: A Dual-Process Model. AB - BACKGROUND/STUDY CONTEXT: In a variety of collaborative circumstances, participants must adopt the perspective of a partner and establish a shared mental representation that helps mediate common understanding. This process is referred to as social coordination. Here, the authors investigate the effect of aging on social coordination and consider separately the component processes related to perspective-taking and working memory. METHODS: Twelve young adults and 14 older adults completed an experimental, language-based coordination task. Subjects were asked to describe a scene with sufficient detail so that a conversational partner could identify a target object in the context of other, competing objects that shared a variable number of features. Trials varied in the information available to the partner (perspective-taking demand) and in the number of competing objects present in the scene (working memory demand). Responses were scored according to adjective use. RESULTS: Results indicated that social coordination performance decreases with age. Whereas young adults performed close to ceiling, older adults were only precise in 49.70% of trials. In analyses examining perspective-taking conditions with no competitors, older adults were consistently impaired relative to young adults; in analyses examining the number of competitors during the simplest perspective-taking condition, both older and younger adults became more impaired with increasing numbers of competitors. CONCLUSION: The experimental data suggest that social coordination decreases with age, which may affect communicative efficacy. Older adults' tendency to provide insufficient responses suggests a limitation in perspective taking, and the pattern of decline in common ground performance with increasing competitors suggests that this is independent of working memory decline. In sum, our results suggest that social coordination deficits in aging may be multifactorial. PMID- 26683046 TI - Muscle power and nutrition. AB - Sarcopenia, as defined by the European working group on sarcopenia in older people (EWGSOP), is a highly prevalent syndrome characterized by age-related loss of muscle mass and muscle strength/power with impacts on physical function, health and quality of life in older people. The complex, multifaceted and still not completely elucidated etiology of sarcopenia and loss of muscle function (dynapenia) poses challenges for the design of interventional studies to combat loss of muscle strength. Several factors, however, have been demonstrated to have major impacts for maintenance of physiological muscle functioning, including nutrition and in particular specific nutrients. For example, proteins, amino acids and micronutrients have been extensively studied regarding their impact on muscle synthesis and metabolism. This literature review focuses on the impact of nutrition on muscle strength and power as it relates to older people given that muscle changes with age can have important implications for health. PMID- 26683047 TI - 'The poor historian': Heart sink? Or time for a re-think? AB - In this commentary article, the oft-heard expression, 'the poor historian', will be discussed. We will consider who the poor historian is and reflect on medical training to speculate how and why the expression has entered the medical lexicon. The potential negative impact of this terminology on patients and junior learners will be considered and strategies for re-framing this concept, for both clinical teachers and learners, will be presented. PMID- 26683048 TI - Use of a frailty index to identify potentially inappropriate prescribing and adverse drug reaction risks in older patients. AB - BACKGROUND: potentially inappropriate prescribing (PIP) is a significant problem in health care today. We hypothesise that if doctors were given a single indicator of PIP and adverse drug reaction (ADR) risk on a patient's prescription, it might stimulate them to review the medicines. We suggest that a frailty index (FI) score may be such a suitable indicator. OBJECTIVES: to determine whether a positive relationship exists between a patient's frailty status, the appropriateness of their medications and their propensity to develop ADRs. Compare this to just using the number of medications a patient takes as an indicator of PIP/ADR risk. SETTING AND METHOD: a frailty index was constructed and applied to a patient database. The associations between a patient's FI score, the number of instances of PIP on their prescription and their likelihood of developing an ADR were determined using Pearson correlation tests and chi(2) tests. RESULTS: significant correlation between FI score instances of PIP was shown (R = 0.92). The mean FI score above which patients experienced at least one instance of PIP was 0.16. Patients above this threshold were twice as likely to experience PIP (OR = 2.6, P < 0.0001) and twice as likely to develop an ADR (OR = 2.1, P < 0.0001). Patients taking more than six medications were 3 times more likely to experience PIP. CONCLUSION: an FI score is a potentially relevant clinical indicator for doctors to critically assess a patient's prescription for the presence of PIP and ultimately prevent ADRs, especially when used in tandem with the number of medications a patient takes. PMID- 26683049 TI - Hospital-acquired pneumonia incidence and diagnosis in older patients. AB - BACKGROUND: hospital-acquired pneumonia poses a hazard to older people who are hospitalised, yet few data exist on the incidence or risk factors in non intensive care patients. This study aimed to determine the incidence of hospital acquired pneumonia (HAP) in a sample of hospitalised older people. METHODS: prospective survey of hospitalised older patients (>65 years) at a single centre over a 12-month period. Casenote and chart data were collected on acute medical, orthopaedic and Medicine for the Elderly wards. HAP was defined in accordance with the European and Scottish National Prevalence Survey 2011 definition. Key analyses were incidence of clinically suspected and case definition clinically confirmed HAP. RESULTS: one thousand three hundred and two patients were included in the analysis. Five hundred and thirty-nine (41%) were male; mean age was 82 years (SD 8). Median length of hospital stay was 14 days (IQR 20). One hundred and fifty-seven episodes of HAP were clinically suspected in 143 patients (10.9% of admissions), but only 83 episodes in 76 patients met the diagnostic criteria (5.8% of admissions). The risk of HAP was 0.3% per day in hospital. Reasons for failure to meet the diagnostic criteria in 75 cases were lack of radiographic evidence in 60/75; lack of evidence of inflammation in 42/75, and lack of respiratory signs or symptoms in 13/75; 35/75 (47%) of cases lacked evidence in two or more domains. CONCLUSION: HAP is common but over-diagnosed in older hospitalised patients. PMID- 26683050 TI - Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. AB - BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). p values were adjusted for multiple testing. RESULTS: Our experiments revealed four main results. First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. Second, in MS patients vs. controls, IgG1 glycosylation patterns were altered in CSF, but not in serum. Specifically, in CSF from the MS group, bisecting GlcNAc were elevated, and afucosylation and galactosylation were reduced. Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. PMID- 26683051 TI - Interpretable functional principal component analysis. AB - Functional principal component analysis (FPCA) is a popular approach to explore major sources of variation in a sample of random curves. These major sources of variation are represented by functional principal components (FPCs). The intervals where the values of FPCs are significant are interpreted as where sample curves have major variations. However, these intervals are often hard for naive users to identify, because of the vague definition of "significant values". In this article, we develop a novel penalty-based method to derive FPCs that are only nonzero precisely in the intervals where the values of FPCs are significant, whence the derived FPCs possess better interpretability than the FPCs derived from existing methods. To compute the proposed FPCs, we devise an efficient algorithm based on projection deflation techniques. We show that the proposed interpretable FPCs are strongly consistent and asymptotically normal under mild conditions. Simulation studies confirm that with a competitive performance in explaining variations of sample curves, the proposed FPCs are more interpretable than the traditional counterparts. This advantage is demonstrated by analyzing two real datasets, namely, electroencephalography data and Canadian weather data. PMID- 26683052 TI - Diagnosis of smear-negative pulmonary tuberculosis based on clinical signs in the Republic of Congo. AB - BACKGROUND: The diagnosis of pulmonary tuberculosis (PTB) and smear-negative pulmonary tuberculosis (SNPT) in resource-limited countries is often solely based on clinical signs, chest X-ray radiography and sputum smear microscopy. We investigated currently used methods for the routine diagnosis of SNPT in the Republic of Congo (RoC) among TB suspected patients. The specific case of HIV positive patients was also studied. METHODS: A cross-sectional study was conducted at the anti-tuberculosis center (CAT) of Brazzaville, RoC. Tuberculosis suspects were examined for physical signs of TB. Clinical signs, results from sputum smear microscopy, tuberculin skin test (TST) and chest X-ray were recorded. RESULTS: Of the 772 enrolled participants, 372 were diagnosed PTB. Cough was a common symptom for PTB and no PTB patients. Pale skin, positive TST, weight loss and chest X-ray with abnormalities compatible with PTB (PTB-CXR) were significant indicators of PTB. Thirty-six percent of PTB patients were diagnosed SNPT. This category of patients presented less persistent cough and less PTB-CXR. Anorexia and asthenia were significant indicators of SNPT. In the case of HIV+ patients, 57% were SNPT with anorexia, asthenia and shorter cough being strong indicators of SNPT. CONCLUSION: Chest X-ray abnormalities, weight loss, pale skin and positive TST were significant indicators of PTB. Anorexia and asthenia showed good diagnostic performance for SNPT, which deserve to be recommended as index indicators of SNPT diagnosis. Duration of cough is also a relevant indicator, especially for HIV+ patients. PMID- 26683053 TI - Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class. AB - Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable. PMID- 26683054 TI - Polyphenols from the extract and fraction of T. indica seeds protected HepG2 cells against oxidative stress. AB - BACKGROUND: Tamarindus indica L. (T. indica) or locally known as "asam jawa" belongs to the family Leguminosae. T. indica seeds as by-products from the fruits were previously reported to contain high polyphenolic content. However, identification of their bioactive polyphenols using recent technologies is less well researched but nonetheless important. Hence, it was the aim of this study to provide further information on the polyphenolic content and antioxidant activities as well as to identify and quantify its bioactive polyphenols. METHODS: T. indica seeds were extracted with methanol and were then fractionated with different compositions of hexane, ethyl acetate and methanol. Polyphenolic contents were measured using Folin-Ciocalteu assay while antioxidant activities were measured using DPPH radical scavenging and ferric reducing (FRAP) activities. The cytotoxic activities of the crude extract and the active fraction were evaluated in HepG2 cells using MTT assay. The cells were then pre-treated with the IC20 concentrations and induced with H2O2 before measuring their cellular antioxidant activities including FRAP, DPPH, lipid peroxidation, ROS generation and antioxidant enzymes, SOD, GPx and CAT. Analyses of polyphenols in the crude extract and its active fraction were done using UHPLC and NMR. RESULTS: Amongst the 7 isolated fractions, fraction F3 showed the highest polyphenolic content and antioxidant activities. When HepG2 cells were treated with fraction F3 or the crude extract, the former demonstrated higher antioxidant activities. F3 also showed stronger inhibition of lipid peroxidation and ROS generation, and enhanced activities of SOD, GPx and CAT of HepG2 cells following H2O2-induced oxidative damage. UHPLC analyses revealed the presence of catechin, procyanidin B2, caffeic acid, ferulic acid, chloramphenicol, myricetin, morin, quercetin, apigenin and kaempferol, in the crude seed extract of T. indica. UHPLC and NMR analyses identified the presence of caffeic acid in fraction F3. Our studies were the first to report caffeic acid as the active polyphenol isolated from T. indica seeds which likely contributed to the potent antioxidant defense system of HepG2 cells. CONCLUSION: Results from this study indicate that caffeic acid together with other polyphenols in T. indica seeds can enhance the antioxidant activities of treated HepG2 cells which can provide protection against oxidative damage. PMID- 26683056 TI - Should Reinke edema be considered a contributing factor to post-extubation failure? PMID- 26683057 TI - A Single-Center, Case-Control Study of Low-Dose-Induction Oral Immunotherapy with Cow's Milk. AB - BACKGROUND: This study aimed to investigate the efficacy and safety of low-dose induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. METHODS: Children aged >=5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. RESULTS: The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. CONCLUSION: This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts. PMID- 26683059 TI - Predicted thermoelectric properties of olivine-type Fe2GeCh4 (Ch = S, Se and Te). AB - We present here the thermoelectric properties of olivine-type Fe2GeCh4 (Ch = S, Se and Te) using the linear augmented plane wave method based on first principles density functional calculations. The calculated transport properties using the semi-local Boltzmann transport equation reveal very high thermopower for both S and Se-based compounds compared to their Te counterparts. The main reason for this high thermopower is the quasi-flat nature of the bands at the valence and conduction band edges. The calculated thermopower of Fe2GeS4 is in good agreement with the experimental reports at room temperature, with the carrier concentration around 10(18)-10(19)cm(-3). All the investigated systems show an anisotropic nature in their electrical conductivity, resulting in a value less than the order of 10(2) along the a-axis compared to the b- and c-axes. Among the studied compounds, Fe2GeS4 and Fe2GeSe4 emerge as promising candidates with good thermoelectric performance. PMID- 26683058 TI - Exploring policy driven systemic inequities leading to differential access to care among Indigenous populations with obstructive sleep apnea in Canada. AB - BACKGROUND: In settler societies such as Australia, Canada, New Zealand and the United States, health inequities drive lower health status and poorer health outcomes in Indigenous populations. This research unravels the dense complexity of how historical policy decisions in Canada can influence inequities in health care access in the 21(st) century through a case study on the diagnosis and treatment of obstructive sleep apnea (OSA). In Canada, historically rooted policy regimes determine current discrepancies in health care policy, and in turn, shape current health insurance coverage and physician decisions in terms of diagnosis and treatment of OSA, a clinical condition that is associated with considerable morbidity in Canada. METHODS: This qualitative study was based in Saskatchewan, a Western Canadian province which has proportionately one of the largest provincial populations of an Indigenous subpopulation (status Indians) which is the focus of this study. The study began with determining approaches to OSA care provision based on Canadian Thoracic Society guidelines for referral, diagnosis and treatment of sleep disordered breathing. Thereafter, health policy determining health benefits coverage and program differences between status Indians and other Canadians were ascertained. Finally, respirologists who specialized in sleep medicine were interviewed. All interviews were audio-recorded and the transcripts were thematically analyzed using NVIVO. RESULTS: In terms of access and provision of OSA care, different patient pathways emerged for status Indians in comparison with other Canadians. Using Saskatchewan as a case study, the preliminary evidence suggests that status Indians face significant barriers in accessing diagnostic and treatment services for OSA in a timely manner. CONCLUSIONS: In order to confirm initial findings, further investigations are required in other Canadian jurisdictions. Moreover, as other clinical conditions could share similar features of health care access and provision of health benefits coverage, this policy analysis could be replicated in other provincial and territorial health care systems across Canada, and other settler nations where there are differential health coverage arrangements for Indigenous peoples. PMID- 26683055 TI - In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans. AB - The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans. PMID- 26683060 TI - Perspectives on Translational Genomics and Public Health in India. AB - It is now recognized worldwide that anticipation and prevention of diseases have significant advantages for the health and healthy ageing of the population. Early recognition of the disease in a vulnerable population such as in children aged <5 years and adults aged >60 years enhances our preparedness for any eventualities and future burden of the diseases to society. It is also recognized that current public health practices alone cannot bring about the desired outcome. When tackling public health-related issues, such problems must be recognized and state of-the-art principles and innovations from genomic sciences, information technologies, and medical specialties must be encompassed and embraced. These will enhance strategies for preparedness and provide us with a better understanding of how to identify, manage, and control disease burdens. The ever expanding landscape of genomics research also includes experimental and computational approaches for effectively utilizing DNA sequence information. From these perspectives, the intricacies of Mendelian single gene disorders are the least challenging compared to intricacies of multi-dimensional host factors for infectious diseases or complex disorders such as cancer. The concepts of public health in India are on firm footing; however, integration of contemporary advances to implement public health principles into practice has neither been attempted nor impacted on disease burden or our preparedness to prevent eventualities. At the same time, translational genomics is gradually paving the way for personalized medicine. Principles of personalized medicine remain to be fully understood and practiced despite the pharmacogenomics-based future of drug development, and treatment has not been as exciting as the advances in genomics we are witnessing today. The relevance, importance, and translational impediments of these advances will be discussed. PMID- 26683061 TI - Glucagon-Like Peptide-1 Receptor Agonist Treatment for Pediatric Obesity. AB - Obesity is a complex and retractable disease for which effective and durable treatments are elusive. Successful treatment of severe obesity with lifestyle modification therapy alone is highly unlikely, particularly for adolescents. Pharmacotherapy, if appropriately prescribed, can be an effective tool to use in conjunction with lifestyle modification therapy to achieve better weight loss outcomes. Only a few obesity medications have been evaluated in children and adolescents with results suggesting modest efficacy. However, a new pipeline of obesity drugs has been recently approved for use among adults. Among these, glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment appears to have reasonable weight loss efficacy along with other beneficial pleiotropic effects. Although larger trials will be required to confirm the results, two small pediatric clinical trials have suggested that GLP-1RA treatment may be useful in adolescents with severe obesity. Once sufficient evidence is generated supporting the safety and efficacy of GLP-1RAs and other obesity medications in youth, the pediatric medical community needs to become less resistant to the use of pharmacotherapy. Otherwise, poor outcomes will continue to be the norm. PMID- 26683062 TI - Electrocortical activity distinguishes between uphill and level walking in humans. AB - The objective of this study was to determine if electrocortical activity is different between walking on an incline compared with level surface. Subjects walked on a treadmill at 0% and 15% grades for 30 min while we recorded electroencephalography (EEG). We used independent component (IC) analysis to parse EEG signals into maximally independent sources and then computed dipole estimations for each IC. We clustered cortical source ICs and analyzed event related spectral perturbations synchronized to gait events. Theta power fluctuated across the gait cycle for both conditions, but was greater during incline walking in the anterior cingulate, sensorimotor and posterior parietal clusters. We found greater gamma power during level walking in the left sensorimotor and anterior cingulate clusters. We also found distinct alpha and beta fluctuations, depending on the phase of the gait cycle for the left and right sensorimotor cortices, indicating cortical lateralization for both walking conditions. We validated the results by isolating movement artifact. We found that the frequency activation patterns of the artifact were different than the actual EEG data, providing evidence that the differences between walking conditions were cortically driven rather than a residual artifact of the experiment. These findings suggest that the locomotor pattern adjustments necessary to walk on an incline compared with level surface may require supraspinal input, especially from the left sensorimotor cortex, anterior cingulate, and posterior parietal areas. These results are a promising step toward the use of EEG as a feed-forward control signal for ambulatory brain computer interface technologies. PMID- 26683064 TI - The effect of experimental low back pain on lumbar muscle activity in people with a history of clinical low back pain: a muscle functional MRI study. AB - In people with a history of low back pain (LBP), structural and functional alterations have been observed at several peripheral and central levels of the sensorimotor pathway. These existing alterations might interact with the way the sensorimotor system responds to pain. We examined this assumption by evaluating the lumbar motor responses to experimental nociceptive input of 15 participants during remission of unilateral recurrent LBP. Quantitative T2 images (muscle functional MRI) were taken bilaterally of multifidus, erector spinae, and psoas at several segmental levels (L3 upper and L4 upper and lower endplate) and during several conditions: 1) at rest, 2) upon trunk-extension exercise without pain, and 3) upon trunk-extension exercise with experimental induced pain at the clinical pain-side (1.5-ml intramuscular hypertonic saline injections in erector spinae). Following experimental pain induction, muscle activity levels similarly reduced for all three muscles, on both painful and nonpainful sides, and at multiple segmental levels (P = 0.038). Pain intensity and localization from experimental LBP were similar as during recalled clinical LBP episodes. In conclusion, unilateral and unisegmental experimental LBP exerts a generalized and widespread decrease in lumbar muscle activity during remission of recurrent LBP. This muscle response is consistent with previous observed patterns in healthy people subjected to the same experimental pain paradigm. It is striking that similar inhibitory patterns in response to pain could be observed, despite the presence of preexisting alterations in the lumbar musculature during remission of recurrent LBP. These results suggest that motor output can modify along the course of recurrent LBP. PMID- 26683063 TI - Oscillatory neural responses evoked by natural vestibular stimuli in humans. AB - While there have been numerous studies of the vestibular system in mammals, less is known about the brain mechanisms of vestibular processing in humans. In particular, of the studies that have been carried out in humans over the last 30 years, none has investigated how vestibular stimulation (VS) affects cortical oscillations. Here we recorded high-density electroencephalography (EEG) in healthy human subjects and a group of bilateral vestibular loss patients (BVPs) undergoing transient and constant-velocity passive whole body yaw rotations, focusing our analyses on the modulation of cortical oscillations in response to natural VS. The present approach overcame significant technical challenges associated with combining natural VS with human electrophysiology and reveals that both transient and constant-velocity VS are associated with a prominent suppression of alpha power (8-13 Hz). Alpha band suppression was localized over bilateral temporo-parietal scalp regions, and these alpha modulations were significantly smaller in BVPs. We propose that suppression of oscillations in the alpha band over temporo-parietal scalp regions reflects cortical vestibular processing, potentially comparable with alpha and mu oscillations in the visual and sensorimotor systems, respectively, opening the door to the investigation of human cortical processing under various experimental conditions during natural VS. PMID- 26683065 TI - Handedness and index finger movements performed on a small touchscreen. AB - Many studies of right/left differences in motor performance related to handedness have employed tasks that use arm movements or combined arm and hand movements rather than movements of the fingers per se, the well-known exception being rhythmic finger tapping. We therefore explored four simple tasks performed on a small touchscreen with relatively isolated movements of the index finger. Each task revealed a different right/left performance asymmetry. In a step-tracking Target Task, left-handed subjects showed greater accuracy with the index finger of the dominant left hand than with the nondominant right hand. In a Center-Out Task, right-handed subjects produced trajectories with the nondominant left hand that had greater curvature than those produced with the dominant right hand. In a continuous Circle Tracking Task, slips of the nondominant left index finger showed higher jerk than slips of the dominant right index finger. And in a continuous Complex Tracking Task, the nondominant left index finger showed shorter time lags in tracking the relatively unpredictable target than the dominant right index finger. Our findings are broadly consistent with previous studies indicating left hemisphere specialization for dynamic control and predictable situations vs. right hemisphere specialization for impedance control and unpredictable situations, the specialized contributions of the two hemispheres being combined to different degrees in the right vs. left hands of right-handed vs. left-handed individuals. PMID- 26683066 TI - Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults. AB - Converging evidence links individual differences in mesolimbic and mesocortical dopamine (DA) to variation in the tendency to choose immediate rewards ("Now") over larger, delayed rewards ("Later"), or "Now bias." However, to date, no study of healthy young adults has evaluated the relationship between Now bias and DA with positron emission tomography (PET). Sixteen healthy adults (ages 24-34 yr; 50% women) completed a delay-discounting task that quantified aspects of intertemporal reward choice, including Now bias and reward magnitude sensitivity. Participants also underwent PET scanning with 6-[(18)F]fluoro-l-m-tyrosine (FMT), a radiotracer that measures DA synthesis capacity. Lower putamen FMT signal predicted elevated Now bias, a more rapidly declining discount rate with increasing delay time, and reduced willingness to accept low-interest-rate delayed rewards. In contrast, lower FMT signal in the midbrain predicted greater sensitivity to increasing magnitude of the Later reward. These data demonstrate that intertemporal reward choice in healthy humans varies with region-specific measures of DA processing, with regionally distinct associations with sensitivity to delay and to reward magnitude. PMID- 26683067 TI - Power spectral analysis of hypoglossal nerve activity during intermittent hypoxia induced long-term facilitation in mice. AB - Power spectral analyses of electrical signals from respiratory nerves reveal prominent oscillations above the primary rate of breathing. Acute exposure to intermittent hypoxia can induce a form of neuroplasticity known as long-term facilitation (LTF), in which inspiratory burst amplitude is persistently elevated. Most evidence indicates that the mechanisms of LTF are postsynaptic and also that high-frequency oscillations within the power spectrum show coherence across different respiratory nerves. Since the most logical interpretation of this coherence is that a shared presynaptic mechanism is responsible, we hypothesized that high-frequency spectral content would be unchanged during LTF. Recordings of inspiratory hypoglossal (XII) activity were made from anesthetized, vagotomized, and ventilated 129/SVE mice. When arterial O2 saturation (SaO2) was maintained >96%, the XII power spectrum and burst amplitude were unchanged for 90 min. Three, 1-min hypoxic episodes (SaO2 = 50 +/- 10%), however, caused a persistent (>60 min) and robust (>400% baseline) increase in burst amplitude. Spectral analyses revealed a rightward shift of the signal content during LTF, with sustained increases in content above ~125 Hz following intermittent hypoxia and reductions in power at lower frequencies. Changes in the spectral content during LTF were qualitatively similar to what occurred during the acute hypoxic response. We conclude that high-frequency content increases during XII LTF in this experimental preparation; this may indicate that intermittent hypoxia induced plasticity in the premotor network contributes to expression of XII LTF. PMID- 26683068 TI - Vestibular contribution to balance control in the medial gastrocnemius and soleus. AB - The soleus (Sol) and medial gastrocnemius (mGas) muscles have different patterns of activity during standing balance and may have distinct functional roles. Using surface electromyography we previously observed larger responses to galvanic vestibular stimulation (GVS) in the mGas compared with the Sol muscle. However, it is unclear whether this difference is an artifact that reflects limitations associated with surface electromyography recordings or whether a compensatory balance response to a vestibular error signal activates the mGas to a greater extent than the Sol. In the present study, we compared the effect of GVS on the discharge behavior of 9 Sol and 21 mGas motor units from freely standing subjects. In both Sol and mGas motor units, vestibular stimulation induced biphasic responses in measures of discharge timing [11 +/- 5.0 (mGas) and 5.6 +/- 3.8 (Sol) counts relative to the sham (mean +/- SD)], and frequency [0.86 +/- 0.6 Hz (mGas), 0.34 +/- 0.2 Hz (Sol) change relative to the sham]. Peak-to-trough response amplitudes were significantly larger in the mGas (62% in the probability based measure and 160% in the frequency-based measure) compared with the Sol (multiple P < 0.05). Our results provide direct evidence that vestibular signals have a larger influence on the discharge activity of motor units in the mGas compared with the Sol. More tentatively, these results indicate the mGas plays a greater role in vestibular-driven balance corrections during standing balance. PMID- 26683069 TI - Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM. AB - Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control. We investigated the motor and locomotor functions of DSCAM(2J) mutant mice through a combination of anatomical, kinematic, force, and electromyographic recordings. With respect to wild-type mice, DSCAM(2J) mice displayed a longer swing phase with a limb hyperflexion at the expense of a shorter stance phase during locomotion. Furthermore, electromyographic activity in the flexor and extensor muscles was increased and coactivated over 20% of the step cycle over a wide range of walking speeds. In contrast to wild-type mice, which used lateral walk and trot at walking speed, DSCAM(2J) mice used preferentially less coordinated gaits, such as out-of-phase walk and pace. The neuromuscular junction and the contractile properties of muscles, as well as their muscle spindles, were normal, and no signs of motor rigidity or spasticity were observed during passive limb movements. Our study demonstrates that the DSCAM mutation induces dystonic hypertonia and a disruption of locomotor gaits. PMID- 26683071 TI - Grids from bands, or bands from grids? An examination of the effects of single unit contamination on grid cell firing fields. AB - Neural recording technology is improving rapidly, allowing for the detection of spikes from hundreds of cells simultaneously. The limiting step in multielectrode electrophysiology continues to be single cell isolation. However, this step is crucial to the interpretation of data from putative single neurons. We present here, in simulation, an illustration of possibly erroneous conclusions that may be reached when poorly isolated single cell data are analyzed. Grid cells are neurons recorded in rodents, and bats, that spike in equally spaced locations in a hexagonal pattern. One theory states that grid firing patterns arise from a combination of band firing patterns. However, we show here that summing the grid firing patterns of two poorly resolved neurons can result in spurious band-like patterns. Thus, evidence of neurons spiking in band patterns must undergo extreme scrutiny before it is accepted. Toward this aim, we discuss single cell isolation methods and metrics. PMID- 26683070 TI - Quantifying the spatial extent of the corollary discharge benefit to transsaccadic visual perception. AB - Extraretinal information, such as corollary discharge (CD), is hypothesized to help compensate for saccade-induced visual input disruptions. However, support for this hypothesis is largely for one-dimensional transsaccadic visual changes, with little comprehensive information on the spatial characteristics. Here we systematically mapped the two-dimensional extent of this compensation by quantifying the insensitivity to different displacement metrics. Human subjects made saccades to targets positioned at different amplitudes (4 degrees or 8 degrees ) and directions (rightward, oblique, or upward). After the saccade the initial target disappeared and, after a blank period, reappeared at a shifted location-a collinear, diagonal, or orthogonal displacement. Subjects reported the perceived shift direction, and we determined the displacement detection based on the perceptual judgments. The two-dimensional insensitivity fields resulting from the perceptual thresholds had spatial features similar to the saccadic eye movement variability: 1) scaled with movement amplitude, 2) oriented (less sensitive to the change) along the saccade vector, and 3) approximately constant in shape when normalized by movement amplitude. In addition, comparing the postsaccadic perceptual estimate of the presaccadic target location to that based solely on the postsaccade visual error showed that overall the perceptual estimate was approximately 50% more accurate and 35% less variable than estimates based solely on this visual information. However, this relationship was not uniform: The benefit of extraretinal information was observed largely for displacements with a component parallel to the saccade vector. These results suggest a graded use of extraretinal information when forming the postsaccadic perceptual evaluation of transsaccadic environmental changes. PMID- 26683072 TI - Human cervical spinal cord circuitry activated by tonic input can generate rhythmic arm movements. AB - The coordination between arms and legs during human locomotion shares many features with that in quadrupeds, yet there is limited evidence for the central pattern generator for the upper limbs in humans. Here we investigated whether different types of tonic stimulation, previously used for eliciting stepping-like leg movements, may evoke nonvoluntary rhythmic arm movements. Twenty healthy subjects participated in this study. The subject was lying on the side, the trunk was fixed, and all four limbs were suspended in a gravity neutral position, allowing unrestricted low-friction limb movements in the horizontal plane. The results showed that peripheral sensory stimulation (continuous muscle vibration) and central tonic activation (postcontraction state of neuronal networks following a long-lasting isometric voluntary effort, Kohnstamm phenomenon) could evoke nonvoluntary rhythmic arm movements in most subjects. In ~40% of subjects, tonic stimulation elicited nonvoluntary rhythmic arm movements together with rhythmic movements of suspended legs. The fact that not all participants exhibited nonvoluntary limb oscillations may reflect interindividual differences in responsiveness of spinal pattern generation circuitry to its activation. The occurrence and the characteristics of induced movements highlight the rhythmogenesis capacity of cervical neuronal circuitries, complementing the growing body of work on the quadrupedal nature of human gait. PMID- 26683073 TI - Perinodal glial swelling mitigates axonal degradation in a model of axonal injury. AB - Mild traumatic brain injury (mTBI) has been associated with the damage to myelinated axons in white matter tracts. Animal models and in vitro studies suggest that axonal degradation develops during a latent period following a traumatic event. This delay has been attributed to slowly developing axonal membrane depolarization that is initiated by injury-induced ionic imbalance and in turn, leads to the activation of Ca(2+) proteases via pathological accumulation of Ca(2+). However, the mechanisms mitigating the transition to axonal degradation after injury remain elusive. We addressed this question in a detailed biophysical model of axonal injury that incorporated ion exchange and glial swelling mechanisms. We show that glial swelling, which often co-occurs with mTBI, promotes axonal survival by regulating extracellular K(+) dynamics, extending the range of injury parameters in which axons exhibit stable membrane potential postinjury. In addition, glial swelling was instrumental in reducing axonal sensitivity to repetitive stretch injury that occurred several minutes following the first one. Results of this study suggest that acute post-traumatic swelling of perinodal astrocytes helps prevent or postpone axonal degradation by maintaining physiologically relevant levels of extracellular K(+). PMID- 26683074 TI - Enhancement of postsynaptic GABAA and extrasynaptic NMDA receptor-mediated responses in the barrel cortex of Mecp2-null mice. AB - Rett syndrome (RTT) is a neurodevelopmental disorder that results from mutations in the X-linked gene for methyl-CpG-binding protein 2 (MECP2). The underlying cellular mechanism for the sensory deficits in patients with RTT is largely unknown. This study used the Bird mouse model of RTT to investigate sensory thalamocortical synaptic transmission in the barrel cortex of Mecp2-null mice. Electrophysiological results showed an excitation/inhibition imbalance, biased toward inhibition, due to an increase in efficacy of postsynaptic GABAA receptors rather than alterations in inhibitory network and presynaptic release properties. Enhanced inhibition impaired the transmission of tonic sensory signals from the thalamus to the somatosensory cortex. Previous morphological studies showed an upregulation of NMDA receptors in the neocortex of both RTT patients and Mecp2 null mice at early ages [Blue ME, Naidu S, Johnston MV. Ann Neurol 45: 541-545, 1999; Blue ME, Kaufmann WE, Bressler J, Eyring C, O'Driscoll C, Naidu S, Johnston MV. Anat Rec (Hoboken) 294: 1624-1634, 2011]. Although AMPA and NMDA receptor mediated excitatory synaptic transmission was not altered in the barrel cortex of Mecp2-null mice, extrasynaptic NMDA receptor-mediated responses increased markedly. These responses were blocked by memantine, suggesting that extrasynaptic NMDA receptors play an important role in the pathogenesis of RTT. The results suggest that enhancement of postsynaptic GABAA and extrasynaptic NMDA receptor-mediated responses may underlie impaired somatosensation and that pharmacological blockade of extrasynaptic NMDA receptors may have therapeutic value for RTT. PMID- 26683076 TI - [Inhaled therapy in asthma]. AB - Because of its advantages, inhaled administration of aerosolized drugs is the administration route of choice for the treatment of asthma and COPD. Numerous technological advances in the devices used in inhaled therapy in recent decades have boosted the appearance of multiple inhalers and aerosolized drugs. However, this variety also requires that the prescribing physician is aware of their characteristics. The main objective of the present review is to summarize the current state of knowledge on inhalers and inhaled drugs commonly used in the treatment of asthma. The review ranges from theoretical aspects (fundamentals and available devices and drugs) to practical and relevant aspects for asthma care in the clinical setting (therapeutic strategies, education, and adherence to inhalers). PMID- 26683075 TI - Single-subject prediction of response inhibition behavior by event-related potentials. AB - Much research has been devoted to investigating response inhibition and the neuronal processes constituting this essential cognitive faculty. However, the nexus between cognitive subprocesses, behavior, and electrophysiological processes remains associative in nature. We therefore investigated whether neurophysiological correlates of inhibition subprocesses merely correlate with behavioral performance or actually provide information expedient to the prediction of behavior on a single-subject level. Tackling this question, we used different data-driven classification approaches in a sample of n = 262 healthy young subjects who completed a standard Go/Nogo task while an EEG was recorded. On the basis of median-split response inhibition performance, subjects were classified as "accurate/slow" and "less accurate/fast." Even though these behavioral group differences were associated with significant amplitude variations in classical electrophysiological correlates of response inhibition (i.e., N2 and P3), they were not predictive for group membership on a single subject level. Instead, amplitude differences in the Go-P2 originating in the precuneus (BA7) were shown to predict group membership on a single-subject level with up to 64% accuracy. These findings strongly suggest that the behavioral outcome of response inhibition greatly depends on the amount of cognitive resources allocated to early stages of stimulus-response activation during responding. This suggests that research should focus more on early processing steps during responding when trying to understand the origin of interindividual differences in response inhibition processes. PMID- 26683077 TI - [Leber hereditary optic neuropathy: Usefulness of next generation sequencing to study mitochondrial mutations on apparent homoplasmy]. AB - BACKGROUND AND OBJECTIVE: Leber hereditary optic neuropathy is characterized by acute and subacute visual loss, produced by mitochondrial DNA mutations. PATIENTS AND METHODS: The molecular study of a family with only one affected member is presented. RESULTS: In the index case and in her mother, the mitochondrial mutation m.11778G>A in the MT-ND4 was detected in the heteroplasmic state. The index case's sister, without ocular manifestations, asked for genetic counseling. The study of the mentioned mutation by Sanger sequencing identified it in an apparent homoplasmic state. However, by means of next-generation sequencing (NGS), the mutation was actually in a heteroplasmic state. CONCLUSIONS: Regarding genetic counseling, verifying a mutation in homoplasmic state is really important. We have observed that NGS allows us to discriminate between high levels of heteroplasmy and homoplasmy, meaning that it is a useful technique for the analysis of apparent homoplasmic results obtained with less sensitive technique, as Sanger sequencing. PMID- 26683078 TI - [Importance of statistical power and hypothesis in P value]. PMID- 26683079 TI - [Spanish validation of the Boston Carpal Tunnel Questionnaire]. AB - INTRODUCTION AND OBJECTIVE: To describe the process of cultural adaptation and validation of the Boston Carpal Tunnel Questionnaire (BCTQ) measuring symptom intensity, functional status and quality of life in carpal tunnel syndrome patients and to report the psychometric properties of this version. MATERIAL AND METHODS: A 3 expert panel supervised the adaptation process. After translation, review and back-translation of the original instrument, a new Spanish version was obtained, which was administered to 2 patient samples: a pilot sample of 20 patients for assessing comprehension, and a 90 patient sample for assessing structural validity (factor analysis and reliability), construct validity and sensitivity to change. A re-test measurement was carried out in 21 patients. Follow-up was accomplished in 40 patients. RESULTS: The questionnaire was well accepted by all participants. Celling effect was observed for 3 items. Reliability was very good, internal consistency: alphaS=0.91 y alphaF=0.87; test retest stability: rS=0.939 and rF=0.986. Both subscales fitted to a general dimension. Subscales correlated with dynamometer measurements (rS=0.77 and rF=0.75) and showed to be related to abnormal 2-point discrimination, muscle atrophy and electromyography deterioration level. Scores properly correlated with other validated instruments: Douleur Neuropatique 4 questions and Brief Pain Inventory. BCTQ demonstrated to be sensitive to clinical changes, with large effect sizes (dS=-3.3 and dF=-1.9). CONCLUSIONS: The Spanish version of the BCTQ shows good psychometric properties warranting its use in clinical settings. PMID- 26683080 TI - Familiarity and priming are mediated by overlapping neural substrates. AB - Explicit memory is widely assumed to reflect the conscious processes of recollection and familiarity. However, familiarity has been hypothesized to be supported by nonconscious processing. In the present functional magnetic resonance imaging (fMRI) experiment, we assessed whether familiarity is mediated by some of the same regions that mediate repetition priming, a form of nonconscious memory. Participants completed an implicit (indirect) memory task and an explicit (direct) memory task during fMRI. During phase I of each task, participants viewed novel abstract shapes with internal colored oriented lines and judged whether each shape was relatively "pleasant" or "unpleasant". During phase II of the indirect memory task, repeated (old) and new shapes were presented and participants made the same judgments. During phase II of the direct memory task, a surprise recognition test was given in which old and new shapes were presented and participants made "remember", "know", or "new" responses. Activity associated with priming was isolated by comparing novel versus repeated shapes during phase II of the indirect memory task. Activity associated with familiarity was isolated by comparing accurate "know" responses versus misses during phase II of the direct memory task. Priming and familiarity were associated with common activity within the superior parietal lobule and motor cortex, which we attribute to shared attentional and motor processing, respectively. The present fMRI results support the hypothesis that familiarity is supported by some of the same processes that support implicit memory. PMID- 26683081 TI - Neural correlates of prosodic boundary perception in German preschoolers: If pause is present, pitch can go. AB - Children's perception of prosodic phrasing provides a head start into the discovery of speech structure. Based on the close prosody-syntax correspondence, children can infer the underlying syntactic structure from the acoustic modulations of prosodic boundaries, typically consisting of co-occurring pitch changes, preboundary lengthening, and pausing. Previous electrophysiological studies revealed that listeners are to some degree flexible in the detection of major prosodic boundaries that are not marked with all three of the suprasegmental cues. Adults and 6-year-olds still showed the brain response for prosodic boundary perception, the Closure Positive Shift (CPS), when pauses marking boundaries were deleted. In contrast, younger children at 3 years did not show this ability yet, but required pausing to complement the other boundary cues. Following the hypothesis that German weights duration cues more heavily than pitch cues, we here examined 3-year-olds' brain responses to prosodic phrasing, testing the role of boundary-related pitch changes. Results revealed that children at this age even showed the CPS in response to pitch-neutralized boundaries with only pausing and preboundary lengthening being present. These results indicate differential roles of acoustic cues in boundary perception, with a preferential reliance on duration cues over pitch changes in 3-year-olds. This preference likely results from the characteristics of the German intonation system and furthers the discussion of cross-linguistic differences in the weighting of prosodic boundary cues. PMID- 26683083 TI - Pedophilic brain potential responses to adult erotic stimuli. AB - Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. PMID- 26683082 TI - Fasudil, a Rho kinase inhibitor, promotes the autophagic degradation of A53T alpha-synuclein by activating the JNK 1/Bcl-2/beclin 1 pathway. AB - Accumulation of alpha-synuclein (alpha-syn) is pivotally implicated in the pathogenesis of Parkinson's disease (PD), and enhancing its clearance might be a promising strategy in PD treatment. It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. However, it is not known if fasudil, the only ROCK inhibitor available in clinical setting, could promote the degradation of alpha-syn, and ameliorate the alpha-syn induced neurotoxicity. In this regard, we investigated the effect of fasudil on neurite injury caused by A53T alpha-syn overexpression and the implicated pathway it might mediate. In the current study, we found that under the condition of A53T alpha-syn overexpression, the neurite outgrowth decreased significantly with the increasing expression of ROCK2. Fasudil, the ROCK inhibitor, ameliorated such neurotoxicity and promoted the clearance of A53T alpha-syn. Its underlying mechanism was supported by that fasudil could increase the macroautophagy activation via JNK 1 and Bcl-2 phosphorylation and beclin 1/Vps34 complex formation. Taken together, fasudil might be able to provide a novel and promising strategy for PD treatment by enhancing alpha-syn clearance and activating the JNK 1/Bcl-2/beclin 1 pathway. PMID- 26683084 TI - Mice null for NEDD9 (HEF1alpha) display extensive hippocampal dendritic spine loss and cognitive impairment. AB - NEDD9 (neural precursor cell expressed, developmentally down-regulated 9) is a member of the CAS (Crk-associated substrate) family of scaffolding proteins that regulate cell adhesion and migration. A Nedd9 knock-out/lacZ knock-in mouse (Nedd9(-/)(-)) was developed in order to study Nedd9 expression and function in the nervous system. Herein we show that NEDD9 is expressed in the adult brain and is prominently expressed in the hippocampus. Behavioral testing uncovered functional deficits in Nedd9(-)(/)(-) mice. In the Morris water maze test, Nedd9( )(/)(-) mice showed deficits in both the ability to learn the task as well as in their ability to recall the platform location. There was no change in the gross morphology of the hippocampus, and stereological analysis of BrdU-labeled newly formed hippocampal cells suggested that this defect is not secondary to altered neurogenesis. However, analysis of the hippocampus revealed extensive loss of dendritic spine density in both the dentate gyrus (DG) and CA1 regions. Spine loss occurred equally across all branch orders and regions of the dendrite. Analysis of spine density in Nedd9(-)(/)(-) mice at 1.5, 6 and 10 months revealed an age-dependent spine loss. This work shows that NEDD9 is required for the maintenance of dendritic spines in the hippocampus, and suggests it could play a role in learning and memory. PMID- 26683085 TI - Neuroanatomic localization of priming effects for famous faces with latency corrected event-related potentials. AB - The late components of event-related brain potentials (ERPs) pose a difficult problem in source localization. One of the reasons is the smearing of these components in conventional averaging because of trial-to-trial latency variability. The smearing problem may be addressed by reconstructing the ERPs after latency synchronization with the Residue Iteration Decomposition (RIDE) method. Here we assessed whether the benefits of RIDE at the surface level also improve source localization of RIDE-reconstructed ERPs (RERPs) measured in a face priming paradigm. Separate source models for conventionally averaged ERPs and RERPs were derived and sources were localized for both early and late components. Jackknife averaging on the data was used to reduce the residual variance during source localization compared to conventional source model fitting on individual subject data. Distances between corresponding sources of both ERP and RERP models were measured to check consistency in both source models. Sources for activity around P100, N170, early repetition effect (ERE/N250r) and late repetition effect (LRE/N400) were reported and priming effects in these sources were evaluated for six time windows. Significant improvement in priming effect of the late sources was found from the RERP source model, especially in the Medio-Temporal Lobe, Prefrontal Cortex, and Anterior Temporal Lobe. Consistent with previous studies, we found early priming effects in the right hemisphere and late priming effects in the left hemisphere. Also, the priming effects in right hemisphere outnumbered the left hemisphere, signifying dominance of right hemisphere in face recognition. In conclusion, RIDE reconstructed ERPs promise a comprehensive understanding of the time-resolved dynamics the late sources play during face recognition. PMID- 26683086 TI - Recurrence of task set-related MEG signal patterns during auditory working memory. AB - Processing of auditory spatial and non-spatial information in working memory has been shown to rely on separate cortical systems. While previous studies have demonstrated differences in spatial versus non-spatial processing from the encoding of to-be-remembered stimuli onwards, here we investigated whether such differences would be detectable already prior to presentation of the sample stimulus. We analyzed broad-band magnetoencephalography data from 15 healthy adults during an auditory working memory paradigm starting with a visual cue indicating the task-relevant stimulus feature for a given trial (lateralization or pitch) and a subsequent 1.5-s pre-encoding phase. This was followed by a sample sound (0.2s), the delay phase (0.8s) and a test stimulus (0.2s) after which participants made a match/non-match decision. Linear discriminant functions were trained to decode task-specific signal patterns throughout the task, and temporal generalization was used to assess whether the neural codes discriminating between the tasks during the pre-encoding phase would recur during later task periods. The spatial versus non-spatial tasks could indeed be discriminated after the onset of the cue onwards, and decoders trained during the pre-encoding phase successfully discriminated the tasks during both sample stimulus encoding and during the delay phase. This demonstrates that task specific neural codes are established already before the memorandum is presented and that the same patterns are reestablished during stimulus encoding and maintenance. This article is part of a Special Issue entitled SI: Auditory working memory. PMID- 26683087 TI - Cryptic Chromosomal Diversity in the Complex "Geophagus" brasiliensis (Perciformes, Cichlidae). AB - Among American cichlids, Geophagus stands out as a species-rich genus widespread over neotropical region. Despite their diversity and confusing taxonomy, only few and basic chromosomal reports are available in populations/species along Atlantic coast, hindering our understanding about evolutionary trends in this genus. Therefore, detailed chromosomal studies were performed in "Geophagus" brasiliensis complex from coastal rivers in northeastern Brazil, totalizing seven populations of Geophagus brasiliensis and one of Geophagus itapicuruensis. All samples shared a diploid number (2n) of 48 divided into 2 submetacentric and 46 subtelocentric/acrocentric chromosomes with (peri)centromeric heterochromatin, hypothesized as a symplesiomorphy for Geophagini. Although G. itapicuruensis and two populations of G. brasiliensis presented single NORs on short arms, multiple GC-rich rDNA sites were observed in the remaining G. brasiliensis samples, ranging from three to six NOR-bearing chromosomes. Inversely, 5S rDNA sites were invariably located at interstitial region on a st/a pair, nonsyntenic to NORs. A compilation of the data set in Geophagus shows that their chromosomal evolution has been driven by pericentric inversions and microstructural changes. Besides, the divergence found in northeastern Brazil places this region as a biodiversity hotspot. A taxonomic revision in the complex "Geophagus" brasiliensis is recommended with the support of cytogenetic analyses. PMID- 26683088 TI - Ultrasound stratification of the FDG-avid thyroid nodule. AB - AIM: To determine whether the malignancy risk in an 2-[(18)F]-fluoro-2-deoxy-d glucose (FDG)-avid thyroid nodule can be stratified according to the presence or absence of suspicious ultrasound features and thereby identify which nodules require further cytological assessment. MATERIALS AND METHODS: A retrospective review of FDG-positron-emission tomography (PET) combined with computed tomography (CT) studies with FDG-avid thyroid nodules (defined as FDG uptake greater than blood pool) that were further assessed with ultrasound and fine needle aspiration cytology or surgery was performed. FDG-avid thyroid nodules were classified as having either suspicious ultrasound features (marked hypo echogenicity, irregular margins, microcalcifications, marked hypervascularity, or nodules that were taller than they were wide) or no suspicious ultrasound features and these findings were correlated with the subsequent cytological results. RESULTS: Forty-eight FDG-avid thyroid nodules were assessed. On cytological assessment five nodules were malignant (10.4%), nine were indeterminate (18.75%), and 34 were benign (70.8%). On ultrasound, 24 (50%) had no suspicious features and 24 (50%) had one or more suspicious features. Of the nodules with no suspicious features, 22 (91.6%) were benign, two (8.3%) were indeterminate, and none were malignant. Of the nodules with suspicious features, five (20.8%) were malignant, seven (29.1%) were indeterminate, and 12 (50%) were benign. The absence of suspicious ultrasound features demonstrated a strong association with benign cytology (p=0.009). Out of the suspicious sonographic features, marked hypoechoic appearance (p=0.02), irregular margins (p=0.009), and taller than wide morphology (p=0.04) were statistically most significantly associated with malignancy. CONCLUSION: The rate of malignancy in FDG-avid thyroid nodules is low in the absence of specific suspicious ultrasound features. The SUV values are non-discriminatory to differentiate between benign and malignant cytology. This suggests that ultrasound can be used to further stratify an FDG-avid thyroid nodule and invasive procedures to investigate the FDG-avid thyroid nodule may not be necessary in the absence of suspicious ultrasound features. PMID- 26683089 TI - Editorial. PMID- 26683090 TI - A comparison of two digital mammography systems: are there any differences? AB - AIM: To compare the performance of two newly introduced digital mammography technologies (Sectra and Hologic) to the Welsh breast-screening service; specifically, whether there are differences in the number, type, size, and grade of tumour identified. MATERIALS AND METHODS: This was a retrospective study of a prospectively collected database of 50,000 consecutive screening episodes from 2012; clients were aged 49-88 years (mean 61.9 years). All studies were double blind read by two readers. All tumours identified in the two arms of the study were detailed and compared specifically with regards to type (ductal or lobular) size, grade, and whether invasive or non-invasive. Performance was analysed for any statistically significant differences. RESULTS: Twenty-five thousand consecutive women were screened with Hologic (recall rate 5.9% of which 18% were cancer) and 25,000 were screened with Sectra digital mammography (recall rate 4.3% and 22% were cancer). Five hundred tumours were found with no significant difference in invasive cancer detection or between ductal or lobular subtypes. The Hologic system detected 267 tumours; of which 81 (30.33%) were non-invasive (3.24 per 1000), compared to the Sectra system with 233 cancers overall including 36 non-invasive (15.45%, 1.44 per 1000). The difference in non-invasive lesions (mainly ductal carcinoma in situ [DCIS]) detection was significant (p<0.001); 38% of which were high nuclear grade (HNG) using Hologic and 50% HNG lesions using Sectra. There was no significant difference in non-invasive size between the two technologies. The mean glandular dose received using the Sectra system was significantly less (0.7 mGy) compared to the Hologic system (1.6 mGy) for a 50-60 mm breast thickness. CONCLUSIONS: Population breast screening is frequently criticised for identifying lesions irrelevant to long-term outcomes or life expectancy and although the two systems seem comparable in terms of invasive cancer detection, a statistically significant difference in the detection of non invasive lesions was seen, not reported in previous studies. This is a contentious issue, as identifying more DCIS has the potential to over-diagnose screened women leading to increased morbidity, higher "cancer detection rates", longer cancer waiting times, and reduced patient psychological wellbeing. The Sectra system is able to deliver a similar invasive detection cancer delivering a much lower dose mammogram, which is important in limiting overall population radiation dose. Further study as to whether the differences in tumour detection rates are clinically significant long term are now required. PMID- 26683091 TI - Commentary on: A comparison of two digital mammography systems: are there any differences? PMID- 26683092 TI - Improving definitions for an index of cumulative organ damage in patients with the antiphospholipid syndrome (DIAPS). PMID- 26683093 TI - Controlled Multi-functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells. AB - A major objective of nanomedicine is to combine in a controlled manner multiple functional entities into a single nanoscale device to target particles with great spatial precision, thereby increasing the selectivity and potency of therapeutic drugs. A multifunctional nanoparticle is described for controlled conjugation of a cytotoxic drug, a cancer cell targeting ligand, and an imaging moiety. The approach is based on the chemical synthesis of polyethylene glycol that at one end is modified by a thioctic acid for controlled attachment to a gold core. The other end of the PEG polymers is modified by a hydrazine, amine, or dibenzocyclooctynol moiety for conjugation with functional entities having a ketone, activated ester, or azide moiety, respectively. The conjugation approach allowed the controlled attachment of doxorubicin through an acid-labile hydrazone linkage, an Alexa Fluor dye through an amide bond, and a glycan-based ligand for the cell surface receptor CD22 of B-cells using strain promoted azide-alkyne cycloaddition. The incorporation of the ligand for CD22 led to rapid entry of the nanoparticle by receptor-mediated endocytosis. Covalent attachment of doxorubicin via hydrazone linkage caused pH-responsive intracellular release of doxorubicin and significantly enhanced the cytotoxicity of nanoparticles. A remarkable 60 fold enhancement in cytotoxicity of CD22 (+) lymphoma cells was observed compared to non- targeted nanoparticles. PMID- 26683095 TI - Approaching the Limits of Strength: Measuring the Uniaxial Compressive Strength of Diamond at Small Scales. AB - Diamond ?100?- and ?111?-oriented nanopillars were fabricated by focused ion beam (FIB) milling from synthetic single crystals and compressed using a larger diameter diamond punch. Uniaxial compressive failure was observed via fracture with a plateau in maximum stress of ~0.25 TPa, the highest uniaxial strength yet measured. This corresponded to maximum shear stresses that converged toward 75 GPa or ~ G/7 at small sizes, which are very close to the ultimate theoretical yield stress estimate of G/2pi. PMID- 26683094 TI - Network-Based Integration of Disparate Omic Data To Identify "Silent Players" in Cancer. AB - Development of high-throughput monitoring technologies enables interrogation of cancer samples at various levels of cellular activity. Capitalizing on these developments, various public efforts such as The Cancer Genome Atlas (TCGA) generate disparate omic data for large patient cohorts. As demonstrated by recent studies, these heterogeneous data sources provide the opportunity to gain insights into the molecular changes that drive cancer pathogenesis and progression. However, these insights are limited by the vast search space and as a result low statistical power to make new discoveries. In this paper, we propose methods for integrating disparate omic data using molecular interaction networks, with a view to gaining mechanistic insights into the relationship between molecular changes at different levels of cellular activity. Namely, we hypothesize that genes that play a role in cancer development and progression may be implicated by neither frequent mutation nor differential expression, and that network-based integration of mutation and differential expression data can reveal these "silent players". For this purpose, we utilize network-propagation algorithms to simulate the information flow in the cell at a sample-specific resolution. We then use the propagated mutation and expression signals to identify genes that are not necessarily mutated or differentially expressed genes, but have an essential role in tumor development and patient outcome. We test the proposed method on breast cancer and glioblastoma multiforme data obtained from TCGA. Our results show that the proposed method can identify important proteins that are not readily revealed by molecular data, providing insights beyond what can be gleaned by analyzing different types of molecular data in isolation. PMID- 26683096 TI - A Comparison of the Batterer Intervention and Prevention Program With Alternative Court Dispositions on 12-Month Recidivism. AB - Studies of batterer intervention and prevention programs (BIPPs) offer mixed results regarding their effect on recidivism. The purpose of this study was to examine the effectiveness of BIPP for cases assigned to a misdemeanor family court. This study focused on determining whether BIPP cases, compared with alternative sanctions, had significantly lower recidivism rates 12 months after program involvement. Findings indicated that BIPP was more effective than jail or regular dismissal in reducing the likelihood of future arrests, but not plea deferred adjudication and conditional dismissal. Results argue toward the efficacy of some form of treatment versus simply receiving jail time. PMID- 26683097 TI - The Effects of Air Pollution and Temperature on COPD. AB - Chronic Obstructive Pulmonary Disease (COPD) affects 12-16 million people in the United States and is the third-leading cause of death. In developed countries, smoking is the greatest risk factor for the development of COPD, but other exposures also contribute to the development and progression of the disease. Several studies suggest, though are not definitive, that outdoor air pollution exposure is linked to the prevalence and incidence of COPD. Among individuals with COPD, outdoor air pollutants are associated with loss of lung function and increased respiratory symptoms. In addition, outdoor air pollutants are also associated with COPD exacerbations and mortality. There is much less evidence for the impact of indoor air on COPD, especially in developed countries in residences without biomass exposure. The limited existing data suggests that indoor particulate matter and nitrogen dioxide concentrations are linked to increased respiratory symptoms among patients with COPD. In addition, with the projected increases in temperature and extreme weather events in the context of climate change there has been increased attention to the effects of heat exposure. Extremes of temperature-both heat and cold-have been associated with increased respiratory morbidity in COPD. Some studies also suggest that temperature may modify the effect of pollution exposure and though results are not conclusive, understanding factors that may modify susceptibility to air pollution in patients with COPD is of utmost importance. PMID- 26683098 TI - Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme. AB - MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile. PMID- 26683099 TI - Angiomirs expression profiling in diffuse large B-Cell lymphoma. AB - Despite advances in treatment, 30% of diffuse large B-cell lymphoma (DLBCL) cases are refractory or relapse after chemoimmunotherapy. Currently, the relationship between angiogenesis and angiomiRs in DLBCL is unknown. We classified 84 DLBCL cases according to stromal signatures and evaluated the expression of pro- and antiangiomiRs in paraffin embedded tissues of DLBCL and correlated them with microvascular density (MVD). 40% of cases were classified as stromal-1, 50% as stromal-2 and 10% were not classified. We observed increased expression of proangiomiRs Let-7f, miR-17, miR-18a, miR-19b, miR-126, miR-130a, miR-210, miR 296 and miR-378 in 14%, 57%, 30%, 45%, 12%, 12%, 56%, 58% and 48% of the cases, respectively. Among antiangiomiRs we found decreased expression of miR-16, miR 20b, miR-92a, miR-221 and miR-328 in, respectively, 27%, 71%, 2%, 44% and 11%. We found association between increased expression of proangiomiRs miR-126 and miR 130a and antiangiomiR miR-328 and the subtype non-GCB. We found higher levels of the antiangiomiRs miR-16, miR-221 and miR-328 in patients with low MVD and stromal-1 signature. IPI and CD34 confirmed independent impact on survival of the study group. None of the above angiomiRs showed significance as biomarker in an independent serum samples cohort of patients and controls. In conclusion, we confirmed association between antiangiomiRs miR-16, miR-221 and miR-328 and stromal-1 signature. Four angiomiRs emerged as potential therapeutic targets: proangiomiRs miR-17, miR-210 and miR-296 and antiangiomiR miR-20b. Although the four microRNAs seem to be important in DLBCL pathogenesis, they were not predictive of DLBCL onset or relapse in the serum independent cohort. PMID- 26683100 TI - Association study of polymorphisms in FOXO3, AKT1 and IGF-2R genes with human longevity in a Han Chinese population. AB - FOXO3, AKT1 and IGF-2R are critical members of the insulin/IGF-1 signaling pathway. Previous studies showed that polymorphisms (SNPs) in FOXO3, AKT1 and IGF 2R were associated with human longevity in Caucasian population. However, the association of these SNPs in different ethnic groups is often inconsistent. Here, we investigated the association of genetic variants in three genes with human longevity in Han Chinese population. Twelve SNPs from FOXO3, AKT1 and IGF-2R were selected and genotyped in 1202 long-lived individuals (nonagenarians and centenarians) and younger individuals. Rs9486902 of FOXO3 was found to be associated with human longevity in both genders combined in this study (allelic P = 0.002, corrected P = 0.024). The other eleven SNPs were not significantly associated with human longevity in Han Chinese population. The haplotypes TTCTT, CCTTC and CTCCT of FOXO3 as well as GGTCGG and GGTCAG of AKT1 were shown to have a significant difference between case and control (P =0.006, 2.78*10-5, 4.68*10 6, 0.003,0.005, respectively). The estimated prevalence of diabetes and prediabetes in long-lived individuals was significantly lower than in common adult populations (P = 0.001, 2.3*10-26) .Therefore, the search for longevity associated genes provides the identification of new potential targets beneficial for the treatment of diabetes. PMID- 26683102 TI - Comment on "Diminishing Returns or Compounding Benefits of Air Pollution Control? The Case of NO(x) and Ozone". PMID- 26683101 TI - Identification of cardiac-related circulating microRNA profile in human chronic heart failure. AB - BACKGROUND: During chronic heart failure, levels of circulating miRNAs endued with characteristics of diseased cells could be identified as biomarkers. In this study, we sought to identify cardiac-related circulating miRNAs as biomarkers of failing heart. METHODS: Total RNA of plasma and heart samples was extracted from 10 normal controls and 14 patients with chronic heart failure. Microarray was applied for miRNA profiles. Validation and organ/tissue distribution analysis was performed by qRT-PCR. In addition, bioinformatics analysis was performed to understand the critical roles of these cardiac-related circulating miRNAs in heart failure. RESULTS: Results showed that levels of more than half of the miRNAs dysregulated in heart failed to show any differences in plasma. Meanwhile, more than 90% of the miRNAs dysregulated in plasma remained stable in heart. Four cardiac fibroblast-derived miRNAs (miR-660-3p, miR-665, miR-1285-3p and miR-4491) were found significantly upregulated in heart and plasma during heart failure. These 4 miRNAs strongly discriminated patients from controls, and 3 of them showed significant correlations with LVEF. CONCLUSIONS: This study provides global profiles of miRNAs changes in plasma and failing heart, and using a circulation-tissue miRNA profiling comparison model, we successfully identify 3 cardiac-related circulating miRNAs as potential biomarkers for diagnosis of heart failure. PMID- 26683103 TI - Refining Target-Controlled Infusion: An Assessment of Pharmacodynamic Target Controlled Infusion of Propofol and Remifentanil Using a Response Surface Model of Their Combined Effects on Bispectral Index. AB - BACKGROUND: Propofol and remifentanil are commonly combined for total IV anesthesia. The pharmacokinetics (PK), pharmacodynamics (PD), and drug interactions of the combination are well understood, but the use of a combined PK and PD model to control target-controlled infusion pumps has not been investigated. In this study, we prospectively tested the accuracy of a PD target controlled infusion algorithm for propofol and remifentanil using a response surface model of their combined effects on Bispectral Index (BIS). METHODS: Effect-site, target-controlled infusions of propofol and remifentanil were given using an algorithm based on standard PK models linked to a PD response surface model of their combined effects on BIS. The combination of a targeted BIS value and adjustable ratio of propofol to remifentanil was used to adjust infusion rates. The standard model performance measures of median performance error (bias) and median absolute performance error (inaccuracy), expressed as percentages, were used to assess accuracy of the infusions in a convenience sample of 50 adult patients undergoing surgery with general anesthesia. The influence of age and weight on the performance of the model was also assessed. RESULTS: Patients had a mean (range) age of 48 (19-73) years, weight of 80 (45-169) kg, and body mass index of 28 (19-45) kg/m. The overall model had a bias of 8% (SD 24%) and inaccuracy of 25% (SD 13%). Performance was least accurate during the early induction phase of anesthesia. There was no significant bias in BIS predictions with increasing age (P = 0.44) or weight (P = 0.56). CONCLUSIONS: The algorithm performed adequately in a clinical setting. The algorithm could be further refined, and assessment of its accuracy and utility in comparison to current clinical practice for giving IV anesthesia is warranted. PMID- 26683104 TI - Trends of Hemoglobin Oximetry: Do They Help Predict Blood Transfusion During Trauma Patient Resuscitation? AB - BACKGROUND: A noninvasive decision support tool for emergency transfusion would benefit triage and resuscitation. We tested whether 15 minutes of continuous pulse oximetry-derived hemoglobin measurements (SpHb) predict emergency blood transfusion better than conventional oximetry, vital signs, and invasive point-of admission (POA) laboratory testing. We hypothesized that the trends in noninvasive SpHb features monitored for 15 minutes predict emergency transfusion better than pulse oximetry, shock index (SI = heart rate/systolic blood pressure), or routine POA laboratory measures. METHODS: We enrolled direct trauma patient admissions >=18 years with prehospital SI >=0.62, collected vital signs (continuous SpHb and conventional pulse oximetry, heart rate, and blood pressure) for 15 minutes after admission, and recorded transfusion (packed red blood cells [pRBCs]) within 1 to 3, 1 to 6, and 1 to 12 hours of admission. One blood sample was drawn during the first 15 minutes. The laboratory Hb was compared with its corresponding SpHb reading for numerical, clinical, and prediction difference. Ten prediction models for transfusion, including combinations of prehospital vital signs, SpHb, conventional oximetry, and routine POA, were selected by stepwise logistic regression. Predictions were compared via area under the receiver operating characteristic curve by the DeLong method. RESULTS: A total of 677 trauma patients were enrolled in the study. The prediction performance of the models, including POA laboratory values and SI (and the need for blood pressure), was better than those without POA values or SI. In predicting pRBC 1- to 3-hour transfusion, adding SpHb features (receiver operating characteristic curve [ROC] = 0.65; 95% confidence interval [CI], 0.53-0.77) does not improve ROC from the base model (ROC = 0.64; 95% CI, 0.52-0.76) with P = 0.48. Adding POA laboratory Hb features (ROC = 0.72; 95% CI, 0.60-0.84) also does not improve prediction performance (P = 0.18). Other POA laboratory testing predicted emergency blood use with ROC of 0.88 (95% CI, 0.81-0.96), significantly better than the use of SpHb (P = 0.00084) and laboratory Hb (P = 0.0068). CONCLUSIONS: SpHb added no benefit over conventional oximetry to predict urgent pRBC transfusion for trauma patients. Both models containing POA laboratory test features performed better at predicting pRBC use than prehospital SI, the current best noninvasive vital signs transfusion predictor. PMID- 26683105 TI - Replicator dynamics of cancer stem cell: Selection in the presence of differentiation and plasticity. AB - The cancer stem cell hypothesis has evolved into one of the most important paradigms in cancer research. According to cancer stem cell hypothesis, somatic mutations in a subpopulation of cells can transform them into cancer stem cells with the unique potential of tumour initiation. Stem cells have the potential to produce lineages of non-stem cell populations (differentiated cells) via a ubiquitous hierarchal division scheme. Differentiation of a stem cell into (partially) differentiated cells can happen either symmetrically or asymmetrically. The selection dynamics of a mutant cancer stem cell should be investigated in the light of a stem cell proliferation hierarchy and presence of a non-stem cell population. By constructing a three-compartment Moran-type model composed of normal stem cells, mutant (cancer) stem cells and differentiated cells, we derive the replicator dynamics of stem cell frequencies where asymmetric differentiation and differentiated cell death rates are included in the model. We determine how these new factors change the conditions for a successful mutant invasion and discuss the variation on the steady state fraction of the population as different model parameters are changed. By including the phenotypic plasticity/dedifferentiation, in which a progenitor/differentiated cell can transform back into a cancer stem cell, we show that the effective fitness of mutant stem cells is not only determined by their proliferation and death rates but also according to their dedifferentiation potential. By numerically solving the model we derive the phase diagram of the advantageous and disadvantageous phases of cancer stem cells in the space of proliferation and dedifferentiation potentials. The result shows that at high enough dedifferentiation rates even a previously disadvantageous mutant can take over the population of normal stem cells. This observation has implications in different areas of cancer research including experimental observations that imply metastatic cancer stem cell types might have lower proliferation potential than other stem cell phenotypes while showing much more phenotypic plasticity and can undergo clonal expansion. PMID- 26683106 TI - The fifth vital sign revisited. PMID- 26683107 TI - Altered brain connectivity in dysmenorrhea: pain modulation and the motor cortex. PMID- 26683108 TI - T-type calcium channel blocker Z944 restores cortical synchrony and thalamocortical connectivity in a rat model of neuropathic pain. AB - Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1. We also hypothesized that the suppression of burst firing in VPL using Z944, a novel T-type calcium channel blocker, restores S1 synchrony and thalamocortical connectivity. Local field potentials were recorded from S1 and VPL in anesthetized rats 7 days after sciatic chronic constriction injury (CCI). In rats with CCI, low-frequency (4-12 Hz) synchrony in S1 was enhanced, whereas VPL-S1 coherence and theta-gamma phase-amplitude coupling were attenuated. Moreover, Granger causality showed decreased informational flow from VPL to S1. Systemic or intrathalamic delivery of Z944 to rats with CCI normalized these changes. Systemic Z944 also reversed thermal hyperalgesia and conditioned place preference. These data suggest that pain-induced cortical synchrony and thalamocortical disconnectivity are directly related to burst firing in VPL. PMID- 26683109 TI - A randomized, phase 2 study investigating TRV130, a biased ligand of the MU opioid receptor, for the intravenous treatment of acute pain. AB - Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the MU-opioid receptor that activates G protein signaling with little beta-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after bunionectomy. We used an adaptive study design in which 144 patients experiencing moderate-to-severe acute pain after bunionectomy were randomized to receive double-blind TRV130, placebo, or morphine in a pilot phase. After pilot phase analysis, 195 patients were randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); placebo; or morphine 4 mg q4h intravenously. The primary end point was the time weighted average change in numeric rating scale pain intensity over the 48-hour treatment period. Secondary end points included stopwatch and categorical assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean reductions in pain intensity than placebo over 48 hours (P < 0.005). TRV130 at 2 and 3 mg produced significantly greater categorical pain relief than morphine (P < 0.005) after the first dose, with meaningful pain relief occurring in under 5 minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. These results demonstrate that TRV130 rapidly produces profound analgesia in moderate-to-severe acute pain, suggesting that G-protein-biased MU-opioid receptor activation is a promising target for development of novel analgesics. PMID- 26683111 TI - Preoperative risk assessment in children undergoing major urologic surgery. AB - BACKGROUND: Preoperative risk assessment is standard in adult surgery, but often these risk assessments cannot be applied to children. Previous studies emphasize the differences between pediatric and adult populations and variability by surgical procedure types. OBJECTIVE: We investigated preoperative risk factors for several outcomes in children undergoing major urologic surgery using the National Surgical Quality Improvement Program (NSQIP) Pediatric. STUDY DESIGN: A cohort of 2-18-year-old children who underwent major urologic surgery was identified by Current Procedure Terminology (CPT) codes in the 2012-2013 NSQIP Pediatric. The NSQIP-Pediatric prospectively collects standardized and validated data from 61 sites on preoperative, operative, and 30-day postoperative variables. Urologic surgeries involving dissection of the peritoneal or extraperitoneal space were included. Patients undergoing pure genitourinary surgery were analyzed separately from those with bowel involvement to improve homogeneity. Postoperative outcomes including hospital length of stay and 30-day infective complications, non-infective complications, unplanned reoperation and readmissions were evaluated by fitting multivariable logistic regression models. RESULTS: A total of 2601 patients were identified, of whom 399 (15.3%) underwent bowel-involved surgery and 2202 (84.7%) underwent pure genitourinary surgery. Patients in the bowel-involved group were significantly older with more comorbidity. Postoperative complications, unplanned return to operating room, hospital length of stay and readmission rates were all significantly worse in the bowel-involved group. In the pure genitourinary group, older age and white race improved some outcomes, while American Society of Anesthesia (ASA) class >= 3, total operation time, obesity, pulmonary risk factors, preoperative renal disease, developmental delay, structural central nervous system abnormality, and supplemental nutrition independently predicted at least one negative outcome (Table). DISCUSSION: Consistent with previous research on reconstructive surgery, we identified a significant difference in patient age, surgery details, comorbidity, and increased complications for patients undergoing urologic surgery with bowel involvement compared with pure genitourinary surgery. Focusing solely on pure genitourinary surgery, we identified predictors of outcomes. Identification of these factors in pediatric urology is novel and only recently possible with the availability of the NSQIP-Pediatric. CONCLUSION: Using the NSQIP-Pediatric, we confirmed differences in complication rates for major urologic surgeries, with and without bowel involvement in a national sample. Preoperative risk characteristics were also identified for patients undergoing pure genitourinary surgery. Further investigation into these relationships is necessary to better elucidate their clinical significance with the goal of improving surgical planning, postoperative care, and family counseling. PMID- 26683112 TI - Commentary to "Imaging and surgical utilization for pediatric cystinuria patients: A single-institution cohort study". PMID- 26683113 TI - Satellite chlorophyll fluorescence measurements reveal large-scale decoupling of photosynthesis and greenness dynamics in boreal evergreen forests. AB - Mid-to-high latitude forests play an important role in the terrestrial carbon cycle, but the representation of photosynthesis in boreal forests by current modelling and observational methods is still challenging. In particular, the applicability of existing satellite-based proxies of greenness to indicate photosynthetic activity is hindered by small annual changes in green biomass of the often evergreen tree population and by the confounding effects of background materials such as snow. As an alternative, satellite measurements of sun-induced chlorophyll fluorescence (SIF) can be used as a direct proxy of photosynthetic activity. In this study, the start and end of the photosynthetically active season of the main boreal forests are analysed using spaceborne SIF measurements retrieved from the GOME-2 instrument and compared to that of green biomass, proxied by vegetation indices including the Enhanced Vegetation Index (EVI) derived from MODIS data. We find that photosynthesis and greenness show a similar seasonality in deciduous forests. In high-latitude evergreen needleleaf forests, however, the length of the photosynthetically active period indicated by SIF is up to 6 weeks longer than the green biomass changing period proxied by EVI, with SIF showing a start-of-season of approximately 1 month earlier than EVI. On average, the photosynthetic spring recovery as signalled by SIF occurs as soon as air temperatures exceed the freezing point (2-3 degrees C) and when the snow on the ground has not yet completely melted. These findings are supported by model data of gross primary production and a number of other studies which evaluated in situ observations of CO2 fluxes, meteorology and the physiological state of the needles. Our results demonstrate the sensitivity of space-based SIF measurements to light-use efficiency of boreal forests and their potential for an unbiased detection of photosynthetic activity even under the challenging conditions interposed by evergreen boreal ecosystems. PMID- 26683115 TI - Our Totally Intra-Articular "Needle-Anchor" Tenodesis Technique Applied in Isolated Long Head of the Biceps Tendinopathy: Clinical and Functional Results in 60 Patients. AB - BACKGROUND: The disorders of the long head of the biceps (LHB) are a common cause of shoulder pain. Among all surgical treatments used to resolve LHB tendon disorders, tenodesis is one of the most frequent.The literature describes many arthroscopic and open surgical techniques, but there is still no general consensus on the standard of care.The purpose of this paper is to describe the clinical and functional outcomes of our totally intra-articular "Needle-Anchor" arthroscopic tenodesis technique applied to isolated LHB tendinopathy. MATERIALS AND METHODS: We present a case study of 60 patients with an isolated LHB tendon disorder, treated with our totally intra-articular Needle-Anchor arthroscopic technique between 2011 and 2013.All patients were assessed preoperatively with University of California, Los Angeles (UCLA) and Constant-Murley (CS) shoulder scores and the visual analogue scale (VAS) for subjective pain assessment. Imaging studies were performed through magnetic resonance imaging. Patients were reevaluated with a follow-up at 3 and 12 months with VAS, UCLA, and CS scores.Statistical analysis was performed with the Mann-Whitney score where values of P<0.05 were considered as significant. RESULTS: CS showed a significant (P<0.05) improvement at 3 and 12 months follow-up, 81.54 +/- 7.5 and 88.90 +/- 5.2, respectively; when compared with preoperative values of 55.14 +/- 9.8.Moreover, the UCLA score showed significant improvement (P<0.05) at the same follow-ups with values of 28.49 +/- 2.1 and 30.88 +/- 1.7, respectively, with preoperative scores of 14.03 +/- 2.4.VAS values were significant at both follow ups, 2.54 +/- 0.2 and 0.58 +/- 0.08, respectively, when compared with preoperative values of 5.34 +/- 0.3. CONCLUSIONS: Biceps tenodesis performed with our Needle-Anchor technique applied to selected patients affected by isolated LHB pathology demonstrated to be effective both in terms of pain and functionality. Moreover, the described technique proved to be reliable, safe, time efficient, easily reproducible, and preserving cosmesis. PMID- 26683116 TI - Interventions to reduce sedentary behavior and increase physical activity during productive work: a systematic review. AB - OBJECTIVE: This review addresses the effectiveness of workplace interventions that are implemented during productive work and are intended to change workers' SB and/or PA. METHODS: We searched Scopus for articles published from 1992 until 12 March 2015. Relevant studies were evaluated using the Quality Assessment Tool for Quantitative Studies and summarized in a best-evidence synthesis. Primary outcomes were SB and PA, both at work and overall (ie, during the whole day); work performance and health-related parameters were secondary outcomes. RESULTS: The review included 40 studies describing 41 interventions organized into three categories: alternative workstations (20), interventions promoting stair use (11), and personalized behavioral interventions (10). Alternative workstations were found to decrease overall SB (strong evidence; even for treadmills separately); interventions promoting stair use were found to increase PA at work while personalized behavioral interventions increased overall PA (both with moderate evidence). There was moderate evidence to show alternative workstations influenced neither hemodynamics nor cardiorespiratory fitness and personalized behavioral interventions did not influence anthropometric measures. Evidence was either insufficient or conflicting for intervention effects on work performance and lipid and metabolic profiles. CONCLUSIONS: Current evidence suggests that some of the reviewed workplace interventions that are compatible with productive work indeed have positive effects on SB or PA at work. In addition, some of the interventions were found to influence overall SB or PA positively. Putative long term effects remain to be established. PMID- 26683114 TI - Spatial navigation by congenitally blind individuals. AB - Spatial navigation in the absence of vision has been investigated from a variety of perspectives and disciplines. These different approaches have progressed our understanding of spatial knowledge acquisition by blind individuals, including their abilities, strategies, and corresponding mental representations. In this review, we propose a framework for investigating differences in spatial knowledge acquisition by blind and sighted people consisting of three longitudinal models (i.e., convergent, cumulative, and persistent). Recent advances in neuroscience and technological devices have provided novel insights into the different neural mechanisms underlying spatial navigation by blind and sighted people and the potential for functional reorganization. Despite these advances, there is still a lack of consensus regarding the extent to which locomotion and wayfinding depend on amodal spatial representations. This challenge largely stems from methodological limitations such as heterogeneity in the blind population and terminological ambiguity related to the concept of cognitive maps. Coupled with an over-reliance on potential technological solutions, the field has diffused into theoretical and applied branches that do not always communicate. Here, we review research on navigation by congenitally blind individuals with an emphasis on behavioral and neuroscientific evidence, as well as the potential of technological assistance. Throughout the article, we emphasize the need to disentangle strategy choice and performance when discussing the navigation abilities of the blind population. For further resources related to this article, please visit the WIREs website. PMID- 26683117 TI - microRNA-16 Is Downregulated During Insulin Resistance and Controls Skeletal Muscle Protein Accretion. AB - Insulin resistant diabetes, currently at epidemic levels in developed countries, begins in the skeletal muscle and is linked to altered protein turnover. microRNAs downregulate targeted mRNA translation decreasing the amount of translated protein, thereby regulating many cellular processes. Regulation of miRNAs and their function in skeletal muscle insulin resistance is largely unexplored. The purpose of this study was to identify the effects of insulin resistance on contents of skeletal muscle miRNAs with potential functions in protein turnover. We examined miRs -1, -16, -23, -27, -133a, -133b, and -206 in muscles of Zucker rats. miR-1 was 5- to 10-fold greater in obesity, whereas miRs 16 and -133b were repressed ~50% in obese compared to lean rats, with no other alterations in miRNA contents. miR-16 correlated to protein synthesis in lean, but not obese rats. miR-16 reduction by lipid overload was verified in-vivo by diet-induced obesity and in-vitro using a diacylglycerol analog. A role for miR 16 in protein turnover of skeletal myocytes was established using transient overexpression and anti-miR inhibition. miR-16 overexpression resulted in lower protein synthesis (puromycin incorporation, ~25-50%), mTOR (~25%), and p70S6K1 (~40%) in starved and insulin stimulated myoblasts. Conversely, anti-miR-16 increased basal protein synthesis (puromycin incorporation, ~75%), mTOR (~100%), and p70S6K1 (~100%). Autophagy was enhanced by miR-16 overexpression (~50% less BCL-2, ~100% greater LC3II/I, ~50% less p62) and impaired with miR-16 inhibition (~45% greater BCL-2, ~25% less total LC3, ~50% greater p62). This study demonstrates reduced miR-16 during insulin resistance and establishes miR-16 control of protein accretion in skeletal muscle. J. Cell. Biochem. 117: 1775 1787, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26683119 TI - Foreword. PMID- 26683118 TI - Balancing conceptions of disability in PND practices: Who, when and how? Response to Aviad Raz commentary: "Uncertain prophecies: How practitioners negotiate the prognostic ambivalence of 'disability' in prenatal diagnosis consultations.". PMID- 26683120 TI - Letter From the Guest Editors: Elder Abuse as a Gendered Issue. PMID- 26683122 TI - An In Vitro Evaluation of Alumina, Zirconia, and Lithium Disilicate Surface Roughness Caused by Two Scaling Instruments. AB - PURPOSE: Plaque control is crucial for the prevention of inflammatory periodontal disease. Hand scaling instruments have been shown to be efficient for the removal of plaque; however, routine periodontal prophylactic procedures may modify the surface profile of restorative materials. The purpose of this study was to assess in vitro the changes in roughness of alumina, zirconia, and lithium disilicate surfaces treated by two hand scaling instruments. MATERIALS AND METHODS: Forty eight alumina specimens, 48 zirconia specimens, and 48 lithium disilicate specimens, were selected. All specimens were divided into three groups of 16 each; one group for each material was considered the control group and no scaling procedures were performed; the second group of each material was exposed to scaling with steel curettes simulating standard clinical conditions; the third group of each material was exposed to scaling with titanium curettes. After scaling, the surface roughness of the specimens was evaluated with a profilometer. First, a statistical test was carried out to evaluate the difference in surface roughness before the scaling procedure of the three materials was effected (Kruskal-Wallis test). Subsequently, the effect of curette material (steel and titanium) on roughness difference and roughness ratio was analyzed throughout the entire sample and within each material group, and a nonparametric test for dependent values was conducted (Wilcoxon signed-rank test). Finally, the roughness ratios of the three material groups were compared by means of a Kruskal-Wallis test and a Wilcoxon signed-rank test. Upon completion of profilometric evaluation, representative specimens from each group were prepared for SEM evaluation to evaluate the effects of the two scaling systems on the different surfaces qualitatively. RESULTS: After scaling procedure, the roughness profile value increased in all disks. Classifying the full sample according to curette used, the roughness of the disks treated with a steel curette reached a higher median value than that of the titanium group. Zirconia demonstrated the least significant increase in surface roughness. The result was 3.9 times of the initial value as compared to 4.3 times for alumina and 4.6 times for lithium disilicate. CONCLUSIONS: Comparison of profilometer readings before and after instrumentation, carried out with different hand scaling instruments, highlighted both a statistically and clinically relevant increase in material roughness. PMID- 26683123 TI - Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields. AB - To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions. PMID- 26683124 TI - Resolving the ambiguity: Making sense of intrinsic disorder when PDB structures disagree. AB - Missing regions in X-ray crystal structures in the Protein Data Bank (PDB) have played a foundational role in the study of intrinsically disordered protein regions (IDPRs), especially in the development of in silico predictors of intrinsic disorder. However, a missing region is only a weak indication of intrinsic disorder, and this uncertainty is compounded by the presence of ambiguous regions, where more than one structure of the same protein sequence "disagrees" in terms of the presence or absence of missing residues. The question is this: are these ambiguous regions intrinsically disordered, or are they the result of static disorder that arises from experimental conditions, ensembles of structures, or domain wobbling? A novel way of looking at ambiguous regions in terms of the pattern between multiple PDB structures has been demonstrated. It was found that the propensity for intrinsic disorder increases as the level of ambiguity decreases. However, it is also shown that ambiguity is more likely to occur as the protein region is placed within different environmental conditions, and even the most ambiguous regions as a set display compositional bias that suggests flexibility. The results suggested that ambiguity is a natural result for many IDPRs crystallized under different conditions and that static disorder and wobbling domains are relatively rare. Instead, it is more likely that ambiguity arises because many of these regions were conditionally or partially disordered. PMID- 26683125 TI - The Implementation of Integrated Behavioral Health Protocols In Primary Care Settings in Project Care. AB - PURPOSE: The majority of adults with mental health (MH) and substance use (SU) disorders in the United States do not receive treatment. The Affordable Care Act will create incentives for primary care centers to begin providing behavioral health (MH and SU) services, thus promising to address the MH and SU treatment gaps. This paper examines the implementation of integrated care protocols by three primary care organizations. METHODS: The Behavioral Health Integration in Medical Care (BHIMC) tool was used to evaluate the integrated care capacity of primary care organizations that chose to participate in the Kern County (California) Mental Health Department's Project Care annually for 3years. For a subsample of clinics, change over time was measured. Informed by the Conceptual Model of Evidence-Based Practice Implementation in Public Service Sectors, inner and outer contextual factors impacting implementation were identified and analyzed using multiple data sources and qualitative analytic methods. RESULTS: The primary care organizations all offered partially integrated (PI) services throughout the study period. At baseline, organizations offered minimally integrated/partially integrated (MI/PI) services in the Program Milieu, Clinical Process - Treatment, and Staffing domains of the BHIMC, and scores on all domains were at the partially integrated (PI) level or higher in the first and second follow-ups. Integrated care services emphasized the identification and management of MH more than SU in 52.2% of evaluated domains, but did not emphasize SU more than MH in any of them. Many of the gaps between MH and SU emphases were associated with limited capacities related to SU medications. Several outer (socio-political context, funding, leadership) and inner (organizational characteristics, individual adopter characteristics, leadership, innovation values fit) contextual factors impacted the development of integrated care capacity. CONCLUSIONS: This study of a small sample of primary care organizations showed that it is possible to improve their integrated care capacity as measured by the BHIMC, though it may be difficult or unfeasible for them to provide fully integrated behavioral health services. Integrated services emphasized MH more than SU, and enhancing primary care clinic capacities related to SU medications may help close this gap. Both inner and outer contextual factors may impact integrated service capacity development in primary care clinics. Study findings may be used to inform future research on integrated care and inform the implementation of efforts to enhance integrated care capacity in primary care clinics. PMID- 26683126 TI - Prospective Randomized Evaluation of Intraoperative Application of Autologous Platelet-Rich Plasma on Surgical Site Infection or Delayed Wound Healing. AB - BACKGROUND: Prevention of surgical site infections and the reduction of wound related complication rates have become increasingly emphasized by hospital task groups and government agencies given the degree of economic burden it places on the health care system. Platelet-rich plasma (PRP) contains growth factors and other biomolecules that promote endogenous microbicidal activity. We hypothesized that PRP would help prevent postoperative infection and delayed wound healing (DWH). METHODS: We randomized patients having foot or ankle surgery to the treatment group receiving intraoperative PRP (applied to operative field) and platelet-poor plasma at closing (PPP, on the sutured skin) or the control group (no PRP/PPP). The incidence of deep surgical site infection and DWH (collectively called endpoints) was compared between groups (n = 250/group). PRP had a mean 5.3 fold platelet concentration compared to whole blood, with concentrated white blood cells. Mean age (+/-SD) of patients was 52 years (+/-15), 65% were women. Minor and major operative procedures were included. Patients were followed for 60 days. Seventy controls had PRP prepared for assay of growth factors. Procedure mix, ASA scores, mean operative times, and comorbidity mix were similar between groups. RESULTS: The primary result was no difference in number of endpoints between groups: 19 patients in the PRP group (7.6%) versus 18 controls (7.2%). Endpoints were deep surgical site infections in 2 PRP/PPP patients and 1 control, and DWH in 17 PRP/PPP patients and 17 controls. Analysis of PRP samples revealed a large variation in growth factor concentrations between patients. CONCLUSIONS: Intraoperative application of PRP/PPP did not reduce the incidence of postoperative infection or DWH. Growth factor profiles varied greatly between patients, suggesting that the potentially therapeutic treatment delivered was not consistent from patient-to-patient. LEVEL OF EVIDENCE: Level I, prospective randomized trial. PMID- 26683127 TI - The successful treatment of refractory respiratory failure due to miliary tuberculosis: survival after prolonged extracorporeal membrane oxygenation support. AB - Acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Although uncommon, pulmonary tuberculosis (TB) can cause ARDS in patients with extensive pulmonary parenchymal involvement. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an accepted alternative option in refractory hypoxemic respiratory failure. It may normalize gas exchange and allow lung rest, avoiding ventilator induced lung injury. We report the case of a 44-year-old woman who developed ARDS secondary to pulmonary TB. Despite anti-TB treatment and mechanical ventilation, patient had persistent refractory hypoxemia. In order to prevent further lung injury, VV-ECMO support was performed for 73 days. Although the patient experienced several complications, patient was successfully managed on VV-ECMO. VV-ECMO support, in combination with anti-TB drugs, is a useful tool in the treatment of ARDS with refractory hypoxemia caused by miliary TB. PMID- 26683128 TI - An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations. AB - In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography-mass spectrometry-specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. The butyr fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetyl-fentanyl and cocaine intoxication, and the manner of death was certified as accident. PMID- 26683129 TI - The cholecystokinin-1 receptor antagonist devazepide increases cholesterol cholelithogenesis in mice. AB - BACKGROUND: A defect in gallbladder contraction function plays a key role in the pathogenesis of gallstones. The cholecystokinin-1 receptor (CCK-1R) antagonists have been extensively investigated for their therapeutic effects on gastrointestinal and metabolic diseases in animal studies and clinical trials. However, it is still unknown whether they have a potential effect on gallstone formation. DESIGN: To study whether the CCK-1R antagonists enhance cholelithogenesis, we investigated cholesterol crystallization, gallstone formation, hepatic lipid secretion, gallbladder emptying function and intestinal cholesterol absorption in male C57BL/6J mice treated by gavage with devazepide (4 mg/day/kg) or vehicle (as controls) twice per day and fed the lithogenic diet for 21 days. RESULTS: During 21 days of feeding, oral administration of devazepide significantly accelerated cholesterol crystallization and crystal growth to microlithiasis, with 40% of mice forming gallstones, whereas only agglomerated cholesterol monohydrate crystals were found in mice receiving vehicle. Compared to the vehicle group, fasting and postprandial residual gallbladder volumes in response to the high-fat meal were significantly larger in the devazepide group during cholelithogenesis, showing reduced gallbladder emptying and bile stasis. Moreover, devazepide significantly increased hepatic secretion of biliary cholesterol, but not phospholipids or bile salts. The percentage of intestinal cholesterol absorption was higher in devazepide-treated mice, increasing the bioavailability of chylomicron-derived cholesterol in the liver for biliary hypersecretion into bile. These abnormalities induced supersaturated bile and rapid cholesterol crystallization. CONCLUSIONS: The potent CCK-1R antagonist devazepide increases susceptibility to gallstone formation by impairing gallbladder emptying function, disrupting biliary cholesterol metabolism and enhancing intestinal cholesterol absorption in mice. PMID- 26683130 TI - PET Imaging in Huntington's Disease. AB - To date, little is known about how neurodegeneration and neuroinflammation propagate in Huntington's disease (HD). Unfortunately, no treatment is available to cure or reverse the progressive decline of function caused by the disease, thus considering HD a fatal disease. Mutation gene carriers typically remain asymptomatic for many years although alterations in the basal ganglia and cortex occur early on in mutant HD gene-carriers. Positron Emission Tomography (PET) is a functional imaging technique of nuclear medicine which enables in vivo visualization of numerous biological molecules expressed in several human tissues. Brain PET is most powerful to study in vivo neuronal and glial cells function as well as cerebral blood flow in a plethora of neurodegenerative disorders including Parkinson's disease, Alzheimer's and HD. In absence of HD specific biomarkers for monitoring disease progression, previous PET studies in HD were merely focused on the study of dopaminergic terminals, cerebral blood flow and glucose metabolism in manifest and premanifest HD-gene carriers. More recently, research interest has been exploring novel PET targets in HD including the state of phosphodiesterse expression and the role of activated microglia. Hence, a better understanding of the HD pathogenesis mechanisms may lead to the development of targeted therapies. PET imaging follow-up studies with novel selective PET radiotracers such as 11C-IMA-107 and 11C-PBR28 may provide insight on disease progression and identify prognostic biomarkers, elucidate the underlying HD pathology and assess novel pharmaceutical agents and over time. PMID- 26683131 TI - A new mandible-specific landmark reference system for three-dimensional cephalometry using cone-beam computed tomography. AB - OBJECTIVES: To develop a novel 3D landmark reference system that is specific for mandibular midline cephalometric landmarks and to assess its repeatability and reproducibility. METHODS: Cone-beam computed tomography (CBCT) scans (3D Accuitomo(r) 170) were performed on 26 dry human skulls. The CBCT data were exported into DICOM files and imported to Maxilim(r) software to create 3D surface models. Two observers identified five landmarks to create a specific mid sagittal mandibular plane: two mandibular foramina, two molar landmarks and one interincisive landmark. On this mid-sagittal mandibular plane, four mandibular cephalometric landmarks were marked: Point B, Pogonion, Gnathion and Menton. All observations were repeated by the two observers after an interval of 4 weeks. The coordinates (x, y, z) of each landmark were exported, and statistical analyses were performed to evaluate inter- and intra-rater precision. RESULTS: The intra observer median precision in locating all landmarks ranged between 0.17 and 0.61mm. The intra-observer repeatability was generally good with a precision under 1mm in more than 50 per cent. The overall median inter-observer precision was 0.26-2.30mm. The mandibular foramina showed the best inter-observer reproducibility. The general inter-observer reproducibility was moderate to good, except for Pogonion and Point B. LIMITATIONS: Dry human skulls may not represent anatomical conditions found in living patients, thus the system should be validated using patients' data. CONCLUSION: The novel reference system offered good precision and generally good to moderate repeatability and reproducibility for mandibular midline cephalometric landmark identification in three dimensions. These findings will be useful for further improvement of 3D cephalometric systems. PMID- 26683132 TI - Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas. AB - The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance. PMID- 26683133 TI - Sequential Use of Transhepatic Arterial Chemoembolization and Bipolar Radiofrequency Ablation in the Clinical Therapy of Hepatocellular Carcinoma. AB - This retrospective study investigated the clinical application of sequential therapy with transarterial chemoembolization (TACE) and CT-guided radiofrequency ablation (RFA) using a bipolar needle in treating hepatocellular carcinoma (HCC) tumors of different sizes. The study included patients (N = 46) with HCC from Shengjing Hospital of China Medical University who had received TACE and RFA from November 2012 to November 2013. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) score of 0-1, a Child-Pugh grade of A-B, and no contradictions for TACE and/or RFA. Fifty one hepatic lesions of varying sizes were treated with TACE followed by RFA. Clinical response and 1- and 2-year survival rates were assessed. The frequency of complete and incomplete ablation following therapy was significantly different across the varying RFA pin numbers and the maximum diameter of the lesion (p <= 0.001). A greater percentage (97.3%) of lesions that were <=3 cm in diameter were completely ablated compared with lesions that were 3-5 cm (88.9%) and >5 cm in diameter (20%). The median survival time of patients was 16.5 months, and the 1- and 2-year survival rates were 95.7% and 69.3%, respectively. There were only a limited number of complications, all of which were minor. These included hemothorax (4.3%), abdominal hemorrhage (10.9%), and abdominal hemorrhage with minor pneumothorax (2.2%). This study found that the sequential treatment with TACE and CT-guided RFA using a bipolar needle is effective and well tolerated in patients with HCC and that the effectiveness of treatment is dependent on tumor size. PMID- 26683134 TI - Lu-177-Labeled Zirconia Particles for Radiation Synovectomy. AB - The present article describes the preparation of beta-emitter lutetium-177 labeled zirconia colloid and its preliminary physicochemical and biological evaluation of suitability for local radionuclide therapy. The new (177)Lu-labeled therapeutic radiopharmaceutical candidate was based on the synthesis mode of a previously described zirconia nanoparticle system. The size and shape of the developed radiopharmaceutical compound were observed through a scanning electron microscope and dynamic light scattering methods. The radiocolloid had a 1.7 MUm mean diameter and showed high in vitro radiochemical and colloid size stability at room temperature and during the blood sera stability test. After the in vitro characterizations, the product was investigated in the course of the treatment of a spontaneously diseased dog veterinary patient's hock joint completed with single-photon emission computed tomography (SPECT) imaging follow-up measurements and a dual-isotope SPECT imaging tests with conventional (99m)Tc methanediphosphonic acid bone scintigraphy. In the treated dog, no clinical side effects or signs of histopathological changes of the joints were recorded during the treatment. SPECT follow-up studies clearly and conspicuously showed the localization of the (177)Lu-labeled colloid in the hock joint as well as detectable but negligible leakages of the radiocolloid in the nearest lymph node. On the basis of biological follow-up tests, the orthopedic team assumed that the (177)Lu-labeled zirconia colloid-based local radionuclide therapy resulted in a significant and long-term improvement in clinical signs of the patient without any remarkable side-effects. PMID- 26683135 TI - Simple and rapid determination of phthalates using microextraction by packed sorbent and gas chromatography with mass spectrometry quantification in cold drink and cosmetic samples. AB - A simple and rapid method using microextraction by packed sorbent coupled with gas chromatography and mass spectrometry has been developed for the analysis of five phthalates, namely, diethyl phthalate, benzyl-n-butyl phthalate, dicyclohexyl phthalate, di-n-butyl phthalate, and di-n-propyl phthalate, in cold drink and cosmetic samples. The various parameters that influence the microextraction by packed sorbent performance such as extraction cycle (extract discard), type and amount of solvent, washing solvent, and pH have been studied. The optimal conditions of microextraction using C18 as the packed sorbent were 15 extraction cycles with water as washing solvent and 3 * 10 MUL of ethyl acetate as the eluting solvent. Chromatographic separation was also optimized for injection temperature, flow rate, ion source, interface temperature, column temperature gradient and mass spectrometry was evaluated using the scan and selected ion monitoring data acquisition mode. Satisfactory results were obtained in terms of linearity with R(2) >0.9992 within the established concentration range. The limit of detection was 0.003-0.015 ng/mL, and the limit of quantification was 0.009-0.049 ng/mL. The recoveries were in the range of 92.35 98.90% for cold drink, 88.23-169.20% for perfume, and 88.90-184.40% for cream. Analysis by microextraction by packed sorbent promises to be a rapid method for the determination of these phthalates in cold drink and cosmetic samples, reducing the amount of sample, solvent, time and cost. PMID- 26683136 TI - Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs. AB - BACKGROUND: Naturally occurring adrenocortical insufficiency (NOAI) in dogs is considered an uncommon disease with good prognosis with hormonal replacement treatment. However, there are no epidemiological studies with estimates for the general dog population. OBJECTIVES: To investigate the epidemiological characteristics of NOAI in a large population of insured dogs. ANIMALS: Data were derived from 525,028 client-owned dogs insured by a Swedish insurance company representing 2,364,652 dog-years at risk (DYAR) during the period between 1995 2006. METHODS: Retrospective cohort study. Incidence rates, prevalences, and relative risks for dogs with NOAI (AI with no previous claim for hypercortisolism), were calculated for the whole dog population, and for subgroups divided by breed and sex. Mortality rates were calculated and compared in dogs with NOAI and the remaining dogs overall. RESULTS: In total 534 dogs were identified with NOAI. The overall incidence was 2.3 cases per 10,000 DYAR. The relative risk of disease was significantly higher in the Portuguese Water Dog, Standard Poodle, Bearded Collie, Cairn Terrier, and Cocker Spaniel compared with other breeds combined. Female dogs overall were at higher risk of developing AI than male dogs (RR 1.85; 95% CI, 1.55-2.22; P < .001). The relative risk of death was 1.9 times higher in dogs with NOAI than in dogs overall. CONCLUSION AND CLINICAL IMPORTANCE: The data supports the existence of breed-specific differences in incidence rates of NOAI in dogs. PMID- 26683137 TI - Clostridium histolyticum collagenase - is this a revolutionary medical treatment for Peyronie's disease? PMID- 26683138 TI - Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma. AB - BACKGROUND: Improved therapies for high-grade glioma (HGG) are urgently needed as the median survival for grade IV gliomas is only 15 months. Bone morphogenetic protein (BMP) signaling plays critical and complex roles in many types of cancer, including glioma, with most of the recently published work focusing on BMP mediated regulation of glioma stem cells (GSCs). We hypothesized that BMP signaling may be an important modulator of tumorigenic properties in glioma cells outside of the GSC compartment. METHODS: We used a human HGG tissue microarray and performed immunohistochemistry for phospho-Smads1,5,8. To examine the role of BMP signaling in tumorigenic astrocytes, transgenic mice were used to delete the BMP type IA receptor (Bmpr1a) and generate astrocytes transformed with oncogenic Ras and homozygous deletion of p53. The cells were transplanted orthotopically into immunocompetent adult host mice. RESULTS: First we established that BMP signaling is active within the vast majority of HGG tumor cells. Mice implanted with BMPR1a-knockout transformed astrocytes showed an increase in median survival compared with mice that received BMPR1a-intact transformed astrocytes (52.5 vs 16 days). In vitro analysis showed that deletion of BMPR1a in oncogenic astrocytes resulted in decreased proliferation, decreased invasion, decreased migration, and increased expression of stemness markers. In addition, inhibition of BMP signaling in murine cells and astrocytoma cells with a small molecule BMP receptor kinase inhibitor resulted in similar tumor suppressive effects in vitro. CONCLUSION: BMP inhibition may represent a viable therapeutic approach in adult HGG. PMID- 26683140 TI - Preview of Immunological Reviews for 2016. PMID- 26683139 TI - Predicting outcome of epilepsy after meningioma resection. AB - BACKGROUND: Surgical excision is the standard treatment for intracranial meningiomas. Epilepsy is a major cause of morbidity in meningioma patients, but postoperative control of epilepsy is not achieved in a substantial fraction of patients. The purpose of this study was to define risk factors for postoperative epilepsy. METHODS: Patients treated for histologically confirmed intracranial meningioma at the University Hospital Zurich between 2000 and 2013 were retrospectively analyzed. Demographic, clinical, imaging, and electroencephalographic data were assessed. A binary regression model was applied to identify risk factors for postoperative epilepsy. RESULTS: Of the 779 patients analyzed, epileptic seizures occurred in 244 (31.3%) patients before surgery and in 204 (26.6%) patients after surgery. Of the 244 patients with preoperative epilepsy, 144 (59.0%) became seizure-free after surgery; of the 535 patients without preoperative seizures, 104 (19.4%) suffered from epilepsy after surgery. Risk factors for postoperative epilepsy were preoperative epilepsy (odds ratio [OR]: 3.46 [95% confidence interval {CI}: 2.32-5.16]), major surgical complications including CNS infections (OR: 5.89 [95% CI: 1.53-22.61]), hydrocephalus (OR: 3.27 [95% CI: 1.35-7.95]), recraniotomy (OR: 2.91 [95% CI: 1.25-6.78]), and symptomatic intracranial hemorrhage (OR: 2.60 [95% CI: 1.17 5.76]) as well as epileptiform EEG potentials (OR: 2.52 [95% CI: 1.36-4.67]), younger age (OR: 1.74 [(95% CI: 1.18-2.58]), and tumor progression (OR: 1.92 [95% CI: 1.16-3.18]). Postoperative improvement or recovery from preoperative neurologic deficits was associated with improved seizure control (OR: 0.46 [95% CI: 0.25-0.85], P = .013). CONCLUSION: We suggest prospective validation of a score ("STAMPE2") based on clinical findings, EEG, and brain-imaging measures to estimate postoperative seizure risk and guide anticonvulsant treatment in meningioma patients. PMID- 26683141 TI - Autoimmunity--promoting and stabilizing innate immunity 'UNWUCHT'. PMID- 26683142 TI - Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo. AB - For decades, research in autoimmunity has focused primarily on immune contributions to disease. Yet recent studies report elevated levels of reactive oxygen species and abnormal activation of the unfolded protein response in cells targeted by autoimmunity, implicating cellular stress originating from the target tissue as a contributing factor. A better understanding of this contribution may help to answer important lingering questions in organ-specific autoimmunity, as to what factors initiate disease and what directs its tissue specificity. Vitiligo, an autoimmune disease of the skin, has been the focus of translational research for over 30 years, and both melanocyte stress and immune mechanisms have been thought to be mutually exclusive explanations for pathogenesis. Chemical induced vitiligo is a unique clinical presentation that reflects the importance of environmental influences on autoimmunity, provides insight into a new paradigm linking cell stress to the immune response, and serves as a template for other autoimmune diseases. In this review, I will discuss the evidence for cell stress contributions to a number of autoimmune diseases, the questions that remain, and how vitiligo, an underappreciated example of organ-specific autoimmunity, helps to answer them. PMID- 26683145 TI - Nucleic acid-sensing TLRs and autoimmunity: novel insights from structural and cell biology. AB - Invasion of pathogenic microorganisms or tissue damage activates innate immune signaling receptors that sample subcellular locations for foreign molecular structures, altered host molecules, or signs of compartment breaches. Upon engagement of innate immune receptors an acute but transient inflammatory response is initiated, aimed at the clearance of pathogens and cellular debris. Among the molecules that are sensed are nucleic acids, which activate several members of the transmembrane Toll-like receptor (TLR) family. Inappropriate recognition of nucleic acids by TLRs can cause inflammatory pathologies and autoimmunity. Here, we review the mechanisms involved in triggering nucleic acid sensing TLRs and indicate checkpoints that restrict their activation to endolysosomal compartments. These mechanisms are crucial to sample the content of endosomes for nucleic acids in the context of infection or tissue damage, yet prevent accidental activation by host nucleic acids under physiological conditions. Decoding the molecular mechanisms that regulate nucleic acid recognition by TLRs is central to understand pathologies linked to unrestricted nucleic acid sensing and to develop novel therapeutic strategies. PMID- 26683144 TI - Apoptotic cell recognition receptors and scavenger receptors. AB - Phosphatidylserine recognition receptors are a highly diverse set of receptors grouped by their ability to recognize the 'eat-me' signal phosphatidylserine on apoptotic cells. Most of the phosphatidylserine recognition receptors dampen inflammation by inducing the production of anti-inflammatory mediators during the phagocytosis of apoptotic corpses. However, many phosphatidylserine receptors are also capable of recognizing other ligands, with some receptors being categorized as scavenger receptors. It is now appreciated that these receptors can elicit different downstream events for particular ligands. Therefore, how phosphatidylserine recognition receptors mediate specific signals during recognition of apoptotic cells versus other ligands, and how this might help regulate the inflammatory state of a tissue is an important question that is not fully understood. Here, we revisit the work on signaling downstream of the phosphatidylserine recognition receptor BAI1, and evaluate how these and other signaling modules mediate signaling downstream from other receptors, including Stabilin-2, MerTK, and alphavbeta5. We also propose the concept that phosphatidylserine recognition receptors could be viewed as a subset of scavenger receptors that are capable of eliciting anti-inflammatory responses to apoptotic cells. PMID- 26683147 TI - The potential role of retroviruses in autoimmunity. AB - In the last 20 years research in Immunology underwent fundamental changes. Most importantly, the identification of the key role of innate immune pattern recognition receptors (PRRs) that recognize evolutionarily conserved molecular patterns on infectious pathogens. This results in priming of innate immune cells, which in turn activate and direct the adaptive immune response. Progress in innate immune recognition instigated the current working hypothesis, that recognition of endogenous ligands by PRRs results in innate immune cell activation (autoinflammation) or activation of adaptive cells, with self-reactive antigen receptors (autoimmunity). In particular, nucleic acid-sensing innate immune receptors seem to be prime candidates for a mechanistic understanding of autoreactive activation of the immune system. However, it remains uncertain what the actual source of nucleic acid ligands is and what other signals are needed to drive activation of autoreactive innate immune cells and break self-tolerance of the adaptive immune system. Here, I will review our present understanding about whether the infection with exogenous retroviruses or the reactivation of endogenous retroviruses might play an etiological role in certain autoimmune conditions of humans and murine experimental models. PMID- 26683146 TI - Endosomal Toll-like receptors in clinically overt and silent autoimmunity. AB - Toll-like receptors (TLRs), first identified as pattern recognition receptors, are now recognized to serve as a key interface between innate and adaptive immunity. Systemic lupus erythematosus (SLE) is characterized by both continuous and cyclic stimulation of the innate and adaptive immune system by endogenous nucleic acids released from apoptotic or necrotic cells. TLR7 and TLR9 function as innate sensors of viral infection as their ligands are ssRNA and dsDNA, respectively. Recognition of self nucleic acids by endosomal TLRs in B cells and pDCs is thought to be an important step in the pathogenesis of SLE, generating anti-nuclear antibodies and producing type I IFN. In this review, we take a specific look at how TLR7, non-coding RNA, and SSA/Ro60 can contribute to clinical autoimmunity and organ damage in the context of neonatal lupus (NL). Although 15 times less common than SLE, NL provides a unique opportunity to study two different aspects of autoimmunity: passively acquired tissue injury in a developing fetus and clinical progression of disease in an asymptomatic mother found to have anti-Ro60 autoantibodies only after identification of heart block/rash in a child. Finally, we discuss hydroxychloroquine (HCQ) use by asymptomatic subjects which may forestall the clinical expression of autoimmunity. PMID- 26683143 TI - Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity. AB - Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in human. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years, it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to systemic lupus erythematosus in a manner analogous to marginal zone macrophages in lupus-prone mice provide an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review, we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans. PMID- 26683149 TI - Age-associated B cells: key mediators of both protective and autoreactive humoral responses. AB - A subset of B cells with unique phenotypic and functional features-termed Age associated B cells (ABCs)-has recently been identified in both mice and humans. These cells are characterized by a T-BET driven transcriptional program, robust responsiveness to TLR7 and TLR9 ligands, and a propensity for IgG2a/c production. Beyond their age-related accumulation, these cells play roles in both normal and pathogenic humoral immune responses regardless of host age. Thus, B cells with the ABC phenotype and transcriptional signature appear during viral, bacterial, and parasitic infections, but also arise during humoral autoimmune disease in both mouse models and humans. These observations suggest that both autoantigens and certain classes of pathogens provide the signals required for ABC differentiation. Herein, we review the discovery and features of ABCs, and propose that they are a memory subset generated by nucleic acid-containing antigens in the context of a promoting inflammatory cytokine milieu. PMID- 26683150 TI - Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. AB - B-cell depletion therapy has beneficial effects in autoimmune diseases. This is only partly explained by an elimination of autoantibodies. How does B-cell depletion improve disease? Here, we review preclinical studies showing that B cells can propagate autoimmune disorders through cytokine production. We also highlight clinical observations indicating the relevance of these B-cell functions in human autoimmunity. Abnormalities in B-cell cytokine production have been observed in rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. In the first two diseases, B-cell depletion erases these abnormalities, and improves disease progression, suggesting a causative role for defective B-cell cytokine expression in disease pathogenesis. However, in the last two disorders, the pathogenic role of B cells and the effect of B-cell depletion on cytokine-producing B cells remain to be clarified. A better characterization of cytokine-expressing human B-cell subsets, and their modulation by B cell-targeted therapies might help understanding both the successes and failures of current B cell-targeted approaches. This may even lead to the development of novel strategies to deplete or amplify selectively pathogenic or protective subsets, respectively, which might be more effective than global depletion of the B-cell compartment. PMID- 26683152 TI - Mechanisms involved in triggering rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory syndrome with a strong autoimmune component. The autoantigens in RA are neither tissue nor organ specific, but comprise a broad collection of post-translational modified proteins, such as citrullinated proteins. These modifications are likely to be triggered by innate stimuli. In genetically susceptible hosts, they can lead to a more substantiated secondary autoimmune reaction targeting the joints and precipitating the clinical onset of RA. Both innate and adaptive mechanisms will then closely interplay to promote chronic joint inflammation in the several absence of appropriate treatment. This scenario, is shared with other autoimmune diseases where potentially pathogenic immune responses are present already before disease onset. Better understanding of these processes will allow both earlier diagnosis of RA and identification of those healthy individuals that are at risk of developing disease, opening possibilities for disease prevention. In this review, we discuss the iterative processes of innate and adaptive immunity responsible for the (longitudinal) development of immune reactions that may contribute to the development of RA. PMID- 26683148 TI - SLE-associated risk factors affect DC function. AB - Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity. PMID- 26683153 TI - The many faces of Mac-1 in autoimmune disease. AB - Mac-1 (CD11b/CD18) is a beta2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcgammaR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE. PMID- 26683151 TI - Sialic acids and autoimmune disease. AB - An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid-containing ligands and recruit SH2 domain-containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells, and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec 2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid-binding proteins are also reviewed. PMID- 26683154 TI - FcgammaRIIB and autoimmunity. AB - Autoimmune diseases are characterized by adaptive immune responses against self antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fcgamma receptors (FcgammaRs). The inhibitory receptor FcgammaRIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in FcgammaRIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which FcgammaRIIB controls the adaptive immune response have been described. Notably, FcgammaRIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of FcgammaRIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of FcgammaRIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity. PMID- 26683156 TI - Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. AB - The current review on the function of neutrophil cytosolic factor 1 (NCF1) and induced reactive oxygen species (ROS) is based on a genetic search for the major genes controlling autoimmune inflammatory disorders. Surprisingly, the disease promoting allele determined a lower ROS response and was therefore in complete contrast to the prevailing dogma. Once cloned, it opened the possibility to dissect this complex field from a new angle and with the possibilities to study the role of ROS in vivo. We found that NCF1 and NADPH oxidase 2 (NOX2) complex derived ROS is an important regulator of several chronic inflammatory disorders by using models for rheumatoid arthritis, multiple sclerosis, psoriasis and psoriasis arthritis, gout, and lupus. ROS could therefore affect many different types of diseases and the common denominator seems to be that ROS regulate macrophages, which prevents inflammation from going chronic. The role of ROS is currently changing from being seen as toxic agents that will promote inflammation toward a more complex view with ROS as crucial regulators of immune and inflammatory pathways. PMID- 26683157 TI - Cytological diagnosis of cardiac masses with ultrasound guided fine needle aspirates. AB - BACKGROUND: Cardiac masses are uncommon in the canine population. When present, an attempt should be made to obtain a definitive diagnosis. Our goal with this case series was to report that as long as anatomic location permits, obtaining fine needle aspirates (FNAs) for cytological evaluation is practical, safe, and may provide a definitive diagnosis. METHODS: Our database has been retrospectively searched for cases where FNA of cardiac masses have been performed. RESULTS: A total of six cases were retrieved. Four dogs were under general anaesthesia and two were sedated. Ultrasound guided transthoracic FNAs were obtained in all cases with only minor complications: mild self-limiting pericardial effusion (n = 1) and one ventricular ectopic complex (n = 1). All dogs were closely monitored during the procedure (pulse oximetry, electrocardiography and blood pressure). A diagnosis was obtained in all cases: inflammation (n = 1), haemangiosarcoma (n = 2), sarcoma (n = 2) and chemodectoma (n = 1). CONCLUSION: A cytological diagnosis allows clinicians to make appropriate clinical decisions, has dramatic impact on treatment recommendations and gives information about prognosis. PMID- 26683169 TI - Mid Staffordshire trust is fined L500,000 for "corporate failure" linked to four deaths. PMID- 26683155 TI - Negative regulation of TLR signaling in myeloid cells--implications for autoimmune diseases. AB - Toll-like receptors (TLR) are transmembrane pattern recognition receptors that recognize microbial ligands and signal for production of inflammatory cytokines and type I interferon in macrophages and dendritic cells (DC). Whereas TLR induced inflammatory mediators are required for pathogen clearance, many are toxic to the host and can cause pathological inflammation when over-produced. This is demonstrated by the role of TLR-induced cytokines in autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Because of the potent effects of TLR-induced cytokines, we have diverse mechanisms to dampen TLR signaling. Here, we highlight three pathways that participate in inhibition of TLR responses in macrophages and DC, and their implications in autoimmunity; A20, encoded by the TNFAIP3 gene, Lyp encoded by the PTPN22 gene, and the BCAP/PI3K pathway. We present new findings that Lyp promotes TLR responses in primary human monocytes and that the autoimmunity risk Lyp620W variant is more effective at promoting TLR-induced interleukin-6 than the non-risk Lyp620R protein. This suggests that Lyp serves to downregulate a TLR inhibitory pathway in monocytes, and we propose that Lyp inhibits the TREM2/DAP12 inhibitory pathway. Overall, these pathways demonstrate distinct mechanisms of negative regulation of TLR responses, and all impact autoimmune disease pathogenesis and treatment. PMID- 26683170 TI - The Corticocortical Structural Connectivity of the Human Insula. AB - The insula is a complex structure involved in a wide range of functions. Tracing studies on nonhuman primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state-of the-art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing an HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro-caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions. PMID- 26683172 TI - Rapid identification of the quality decoction pieces by partial least squares based pattern recognition: grade classification of the decoction pieces of Saposhnikovia divaricata. AB - Herbal medicines are commonly used in many countries after they undergo processing. Quality decoction pieces are a guarantee of the efficacy and safety of the herbal medical products. Here, a strategy based on chemical analysis combined with chemometric techniques was proposed for the classification and prediction of the different grades of the decoction pieces. Considering the necessity for a shared and simple method for the grade classification for the public, in this paper, the characterization of the chemical constituents was determined by utilizing high-performance liquid chromatography (HPLC)/diode array detection. HPLC was first established for the characterization of the chemical constituents of the different grade decoction pieces. Furthermore, a simultaneous quantification of several of the marker compounds in these decoction pieces was obtained. Finally, a partial least squares-based pattern recognition method was utilized to obtain a predictive model for the grade classification of the decoction pieces. Saposhnikovia divaricata (Turcz.) Schischk was used as a case study. The partial least squares -based pattern recognition for the grade classification of the decoction pieces of S. divaricata demonstrated good sensitivity, specificity and prediction performance, which may efficiently validate the identification results of appearance assessment. The proposed strategy is expected to provide a new insight for the grade classification and quality control of the decoction pieces. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26683171 TI - Experience Shapes the Development of Neural Substrates of Face Processing in Human Ventral Temporal Cortex. AB - In adult humans, the ventral temporal cortex (VTC) represents faces in a reproducible topology. However, it is unknown what role visual experience plays in the development of this topology. Using functional magnetic resonance imaging in children and adults, we found a sequential development, in which the topology of face-selective activations across the VTC was matured by age 7, but the spatial extent and degree of face selectivity continued to develop past age 7 into adulthood. Importantly, own- and other-age faces were differentially represented, both in the distributed multivoxel patterns across the VTC, and also in the magnitude of responses of face-selective regions. These results provide strong evidence that experience shapes cortical representations of faces during development from childhood to adulthood. Our findings have important implications for the role of experience and age in shaping the neural substrates of face processing in the human VTC. PMID- 26683173 TI - Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study. AB - OBJECTIVE: Abnormal brain networks have been observed in patients with obsessive compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole brain functional networks. METHODS: We used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. RESULTS: OCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico-striato-thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. CONCLUSION: Our results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD. PMID- 26683174 TI - Treatment-refractory obsessive compulsive disorder. PMID- 26683175 TI - CCL22-specific Antibodies Reveal That Engagement of Two Distinct Binding Domains on CCL22 Is Required for CCR4-mediated Function. AB - CCL22 inactivation in vivo occurs by cleavage at the N-terminus; however, it is unclear whether this encompasses the entire site of CCR4 interaction. CCL17 also binds CCR4 and its function requires binding via two discrete binding sites. Using monoclonal antibodies (MAbs), we report that there are two separate sites on CCL22 that are required for CCR4-mediated function. The CCL22-specific antibodies bind with affinities of 632 +/- 297 pM (MC2B7) and 308 +/- 43 pM (MAB4391) and neither exhibited detectable binding to CCL17. Both antibodies are comparable in their ability to inhibit CCL22-mediated calcium mobilization; however, competition binding studies demonstrate that MC2B7 and MAB4391 bind to distinct epitopes on CCL22. Both antibodies inhibit function through CCR4, which is demonstrated by loss of beta-arrestin recruitment in a reporter cell line. In both assays, blocking either site independently abolished CCL22 function, suggesting that concurrent engagement of both sites with CCR4 is necessary for function. This is the first demonstration that CCL22 has two distinct binding sites that are required for CCR4 function. These antibodies are valuable tools for better understanding the interaction and function of CCL22 and CCR4 and will potentially help further understanding of the differential outcomes of CCL17 and CCL22 interaction with CCR4. PMID- 26683176 TI - Inducing Humoral Immune Responses Against Regulatory T Cells by Foxp3-Fc(IgG) Fusion Protein. AB - The existence of a developed network of suppressory factors and cells against an immune response in different cancers has been proven; regulatory T cells are a typical issue. Therefore their depletion, elimination, or suppression has been assessed in different research studies that were not entirely successful. By applying an improved vaccine against regulatory T cells, we have evaluated the B cell response elicited by the vaccine in an experimental design. A previously described DNA vaccine and recombinant protein of Foxp3-Fc fusion were produced and used in the vaccination regimen. DNA construct and respective protein were injected into C57BL/6 mice. After 2 weeks, serum levels of IgG antibody and its subtypes against Foxp3 were investigated by ELISA. To produce recombinant Foxp3 for ELISA antigen coating, pET24a-Foxp3 vector was transformed into Escherichia coli strain BL21 as host cells. Afterward, protein was expressed and then purified using Ni-NTA agarose. SDS-PAGE and Western blot analysis were carried out to confirm protein expression. The expression analysis of Foxp3 was confirmed by SDS-PAGE followed by Western blot analysis. FOXP3-Fc DNA vaccine/fusion protein vaccination regimen could induce T helper-dependent humoral responses. Due to the effectiveness of Foxp3-Fc(IgG) in inducing humoral responses, it would be expected to be useful in developing vaccines in tumor therapies for the removal of regulatory T cells as a strategy for increasing the efficiency of other means of immunotherapy. PMID- 26683177 TI - Monoclonal Antibodies Against Porcine sIgA and Their Use in Immunohistochemistry. AB - Secretory IgA (sIgA) is known as the predominant immunoglobulin in the mucosal system. It prevents pathogens from invading an animal's body through mucosa, making homeostasis. However, few studies examining the secretion of sIgA in mucosal-associated tissues of porcines based on immunohistochemistry methods have been done. In this study, BALB/c mice were immunized with porcine sIgA and the splenocytes were then fused with myeloma cells. Finally, three hybridoma cell lines secreting monoclonal antibody (MAb) against porcine sIgA were obtained. All three MAbs had no cross-reaction with porcine IgG confirmed by Western blot analysis. Furthermore, lungs, tracheas, and intestines were collected from healthy porcines to prepare tissue slices, followed by incubation with the MAb produced in this study. The results showed that sIgA existing in respiratory and digestive systems could be detected by this newly produced MAb. These generated MAbs against porcine sIgA might have a potential use in mucosal research of porcines. PMID- 26683178 TI - Production and Characterization of a Novel Monoclonal Antibody Against Human Sortilin. AB - Sortilin, as a member of Vps10p-domain sorting receptor family, is overexpressed in a number of malignancies, including ovarian carcinoma. Antibodies against sortilin may contribute to further clarification of sortilin functional activities in signal transduction, intracellular sorting of proteins, and endocytosis. The aim of this study was to produce a monoclonal antibody against a synthetic peptide derived from extracellular N-terminal region of sortilin to be used as a tool for investigating sortilin characteristics in ovarian carcinoma. A synthetic peptide derived from the last 50 amino acids of extracellular domain of sortilin protein was selected and conjugated to keyhole limpet hemocyanin and used to immunize mice. The anti-sortilin monoclonal antibody (MAb), clone 2D8, was purified from supernatant of final hybridoma clone using peptide-affinity chromatography column. Reactivity of antibody with the immunizing peptide was assessed in ELISA. Furthermore, flow cytometry and Western blot analyses were used to investigate the reactivity of antibody with its target in a panel of ovarian carcinoma cell lines or tissues. MAb 2D8 was able to recognize the coated immunizing peptide in ELISA and detect its protein target, sortilin, in flow cytometry and Western blot analyses. The achieved data suggest that the developed monoclonal antibody may be applicable as a research tool for detection of sortilin protein in Western blot as well as flow cytometry tests. PMID- 26683179 TI - Development of Sensitive Monoclonal Antibody PMab-2 Against Rat Podoplanin. AB - Podoplanin (PDPN) is a platelet aggregation-inducing factor, which is known as an endogenous ligand of C-type lectin-like receptor-2 (CLEC-2). PDPN is also expressed in several normal tissues, such as lung type I alveolar cells and kidney podocytes. Although many monoclonal antibodies (MAbs) against human PDPN (hPDPN) or mouse PDPN (mPDPN) have been established, anti-rat PDPN (rPDPN) MAbs, especially against platelet aggregation-stimulating (PLAG) domain (29-54 amino acids) of rPDPN, have not been developed. Therefore, functional analysis of rPDPN in normal tissues has been limited. Here, we immunized mice with rPDPN peptides (38-51 amino acids) and developed a novel mouse anti-rPDPN MAb, PMab-2 (IgG1, kappa), which possesses high affinity compared with anti-hPDPN or mPDPN MAbs. The KD of PMab-2 was determined to be 5.9 * 10(-10) M. PMab-2 is useful, not only in flow cytometry and Western blot analysis against endogenous rPDPN, which is expressed in rat dermal fibroblast, but also in immunohistochemistry against normal tissues. PMab-2 showed extraordinarily high sensitivity in immunohistochemistry, indicating that PMab-2 is very advantageous for functional analysis of rPDPN. PMID- 26683181 TI - Generation and Characterization of Rat Monoclonal Antibodies Against Epidermal Growth Factor Receptor. AB - Overexpression of the epidermal growth factor receptor (EGFR) gene and dysregulation of EGFR signaling are observed in various cancer cells, and EGFR is a validated target for cancer therapy. In the present study, we report on the generation of two rat anti-EGFR antibodies (clones 2C2D3 and 4H7F4) by using the rat lymph node method. Flow cytometric analysis and immunofluorescence showed that both antibodies specifically bound to EGFR on the surface of cancer cells. Competitive analysis demonstrated that the epitope of each antibody had no overlap with that of the therapeutic anti-EGFR antibody cetuximab. These results suggest that 2C2D3 and 4H7F4 are potentially useful in EGFR-targeted cancer therapy. PMID- 26683180 TI - Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application. AB - Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3 D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma. PMID- 26683182 TI - Establishment of a Mouse Anti-ovalbumin IgE Monoclonal Antibody That Induces FcERII (CD23)-dependent Activation Without FcERI-Dependent Activation. AB - IgE mainly activates cells via two receptors, FcERI and FcERII. Blocking antibodies against and animals genetically targeted for these receptors have been successfully used to distinguish between these two activating pathways. In the present study, we investigated whether our newly established anti-ovalbumin (OVA) monoclonal IgE OE-2 induced FcERII-dependent activation, but not FcERI-dependent activation in vivo and in vitro, in contrast to the previously established anti OVA IgE OE-1, which stimulated FcERI and FcERII. The FcERI-mediated degranulation of RBL2H3 cells and passive systemic anaphylaxis in mice were induced by OE-1 but not OE-2. On the other hand, the production of nitric oxide by rat peritoneal macrophages and the primary antibody response in mice against co-injected OVA, which were mediated through FcERII, were induced and enhanced by OE-1 and OE-2. Differences in the epitopes recognized by OE-1 and OE-2 may partially explain why OE-1, but not OE-2, triggered FcERI-dependent activation. OE-1 bridged FcERI through effective aggregation with OVA, whereas OE-2 crosslinked the receptor strongly and only moderately upon the addition of an anti-kappa antibody and polymerized OVA, namely, an OVA-conjugated resin, respectively, resulting in degranulation. Our results offer a novel approach for determining the relative importance of FcERI and FcERII in various IgE-dependent responses by using OE-1 and OE-2. PMID- 26683183 TI - Preparation of Monoclonal Antibodies Against SpiC Protein Secreted by T3SS-2 of Salmonella spp. AB - SpiC protein, a member of Salmonella spp. type III secretion system (T3SS)-2, is necessary for the survival of Salmonella within macrophages, and it plays a vital role in Salmonella pathogenesis. To develop and test monoclonal antibodies (MAbs) against SpiC protein, two recombinant proteins, rHis-SpiC and rGST-SpiC, were expressed in vitro in the prokaryotic expression vectors pET-30(a) and pGEX-6p-1, respectively, and rHis-SpiC protein used to immunize mice. Hybridomas were generated from the splenocytes of these mice and the monoclonal antibodies produced by these cells were assessed using indirect enzyme-linked immunosorbent assay (ELISA) with rGST-SpiC as the coating antigen. An immunoblotting analysis indicated that all seven of the MAbs developed in this study could specifically recognize the SpiC protein. These MAbs will be very useful in the study of SpiC function and for use in the immunodiagnosis of Salmonella infection. PMID- 26683184 TI - Generation and Characterization of Monoclonal Antibodies Specific to Avian Influenza H5N1 Hemagglutinin Protein. AB - Highly pathogenic avian influenza (HPAI) H5N1 virus has in the past breached the species barrier from infected domestic poultry to humans in close contact. Although human-to-human transmission has previously not been reported, HPAI H5N1 virus has pandemic potential owing to gain of function mutation(s) and/or genetic reassortment with human influenza A viruses. Monoclonal antibodies (MAbs) have been used for diagnosis as well as specific therapeutic candidates in several disease conditions including viral infections in humans. In this study, we describe the preliminary characterization of four murine MAbs developed against recombinant hemagglutinin (rHA) protein of avian H5N1 A/turkey/Turkey/1/2005 virus that are either highly specific or broadly reactive against HA from other H5N1 subtype viruses, such as A/Hong Kong/213/03, A/Common magpie/Hong Kong/2256/2006, and A/Barheaded goose/Quinghai/14/2008. The antibody binding is specific to H5N1 HAs, as none of the antibodies bound H1N1, H2N2, H3N2, or B/Brisbane/60/2008 HAs. Out of the four MAbs, one of them (MA-7) also reacted weakly with the rHA protein of H7N9 A/Anhui/1/2013. All four MAbs bound H5 HA (A/turkey/Turkey/1/2005) with high affinity with an equilibrium dissociation constant (KD) ranging between 0.05 and 10.30 nM. One of the MAbs (MA-1) also showed hemagglutination inhibition activity (HI titer; 31.25 MUg/mL) against the homologous A/turkey/Turkey/1/2005 H5N1 virus. These antibodies may be useful in developing diagnostic tools for detection of influenza H5N1 virus infection. PMID- 26683189 TI - Female-Driven Multiple Concurrent Sexual Partnership Systems in a Rural Part of a Southern Tanzanian Province. AB - BACKGROUND: Multiple concurrent sexual relationships are one of the major challenges to HIV prevention in Tanzania. This study aims to explore sexual behaviour patterns including the practice of multiple concurrent sexual partnerships in a rural Tanzanian setting. METHODS: This qualitative study used focus group discussions and in-depth interviews with men and women from the community as well as ethnographic participant observations. The data was collected during 16 months of fieldwork in 2007, 2008, and 2009. The focus group discussions and in-depth interviews were transcribed verbatim and translated into English. The data was analysed through the process of latent content analysis. An open coding coding process was applied to create categories and assign themes. FINDINGS: Mafiga matatu was an expression used in this society to describe women's multiple concurrent sexual partners, usually three partners, which was described as a way to ensure social and financial security for their families as well as to achieve sexual pleasure. Adolescent initiation ceremonies initiated and conducted by grand mothers taught young women why and how to engage successfully in multiple concurrent sexual relationships. Some men expressed support for their female partners to behave according to mafiga matatu, while other men were hesitant around this behaviour. Our findings indicate that having multiple concurrent sexual partners is common and a normative behaviour in this setting. Economical factors and sexual pleasure were identified as drivers and viewed as legitimate reason for women to have multiple concurrent sexual partnerships. CONCLUSIONS: Structural changes improving women's financial opportunities and increasing gender equality will be important to enable women to not depend on multiple concurrent sexual partnerships for financial security. Future research should explore how normative sexual behaviour changes as these structural changes take place. PMID- 26683190 TI - Plasma Ascorbic Acid, A Priori Diet Quality Score, and Incident Hypertension: A Prospective Cohort Study. AB - Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other's predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995-1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 MUmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-MUmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79 0.92) and per 12-points higher diet score 0.86 (95% CI 0.79-0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion. PMID- 26683191 TI - miR-sc8 Inhibits Schwann Cell Proliferation and Migration by Targeting Egfr. AB - MicroRNAs (miRNAs) negatively regulate the expression of target genes at the post transcriptional level in diverse biological processes. We have previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection by Solexa sequencing. In this study, the biological function and action mode of miR-sc8, one of the above identified miRNAs, were investigated. An increased expression of miR-sc8 inhibited cell proliferation and migration of Schwann cells (SCs), and inversely, silencing of the miR-sc8 expression promoted cell proliferation and migration of SCs. The epidermal growth factor receptor (Egfr) was identified as the target gene of miR-sc8, which exerted negative regulation of Egfr by translational suppression. The temporal change profile of the miR-sc8 expression was negatively correlated with that of the Egfr expression in proximal nerve following sciatic nerve transection. Moreover, Knockdown of Egfr attenuated the promoting effects of miR-sc8 inhibitor on SC proliferation and migration. Overall, our data indicate that miR-sc8 affects phenotype modulation of SCs by targeting Egfr, providing further insights into the regulatory role of miRNAs in peripheral nerve regeneration. PMID- 26683192 TI - Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients. PMID- 26683194 TI - 2015 EULAR-ACR recommendations for polymyalgia rheumatica: the message and next steps. PMID- 26683195 TI - In rheumatoid arthritis, country of residence has an important influence on fatigue: results from the multinational COMORA study. AB - OBJECTIVES: To investigate the relationship between country of residence and fatigue in RA, and to explore which country characteristics are related to fatigue. METHODS: Data from the multinational COMORA study were analysed. Contribution of country of residence to level of fatigue [0-10 on visual analogue scale (VAS)] and presence of severe fatigue (VAS ? 5) was explored in multivariable linear or logistic regression models including first socio demographics and objective disease outcomes (M1), and then also subjective outcomes (M2). Next, country of residence was replaced by country characteristics: gross domestic product (GDP), human development index (HDI), latitude (as indicator of climate), language and income inequality index (gini index). Model fit (R(2)) for linear models was compared. RESULTS: A total of 3920 patients from 17 countries were included, mean age 56 years (s.d. 13), 82% females. Mean fatigue across countries ranged from 1.86 (s.d. 2.46) to 4.99 (s.d. 2.64) and proportion of severe fatigue from 14% (Venezuela) to 65% (Egypt). Objective disease outcomes did not explain much of the variation in fatigue ([Formula: see text] = 0.12), while subjective outcomes had a strong negative impact and partly explained the variation in fatigue ([Formula: see text]= 0.27). Country of residence had a significant additional effect (increasing model fit to [Formula: see text] = 0.20 and [Formula: see text] = 0.36, respectively). Remarkably, higher GDP and better HDI were associated with higher fatigue, and explained a large part of the country effect. Logistic regression confirmed the limited contribution of objective outcomes and the relevant contribution of country of residence. CONCLUSION: Country of residence has an important influence on fatigue. Paradoxically, patients from wealthier countries had higher fatigue. PMID- 26683193 TI - Impact of gout on the risk of atrial fibrillation. AB - OBJECTIVES: To examine the risk of atrial fibrillation (AF) at the time of first diagnosis of gout compared with matched controls and to follow incident gout patients and their matched controls after diagnosis to compare their subsequent risk of AF. METHODS: From the UK Clinical Practice Research Data-link, 45 378 incident gout patients and 45 378 age-, sex-, practice-, registration year- and index year-matched controls were identified. Index dates were initial diagnosis date for gout patients and their matched controls. The risk of AF at diagnosis [odds ratios (ORs), using conditional logistic regression] and after the diagnosis of gout [hazard ratios (HRs), using Cox proportional models] were estimated, adjusted for BMI, smoking, alcohol consumption, ischaemic heart disease, heart failure, heart valve disease, hyperthyroidism and other comorbidities and medications. RESULTS: The prevalence of AF at index date in gout patients (male, 72.3%; mean age, 62.4 +/- 15.1 years) was 7.42% (95% CI 7.18, 7.66%) and in matched controls 2.83% (95% CI 2.67, 2.98%). The adjusted OR (95% CI) was 1.45 (1.29, 1.62). The cumulative probability of AF at 1, 2, 5 and 10 years after index date was 1.08, 2.03, 4.77 and 9.68% in gout patients and 0.43, 1.08, 2.95 and 6.33% in controls, respectively (log-rank test, P < 0.001). The adjusted HR (95% CIs) was 1.09 (1.03, 1.16). CONCLUSION: This population based study indicates that gout is independently associated with a higher risk of AF at diagnosis and the risk is also higher after the diagnosis. PMID- 26683196 TI - Does disease activity at start of biologic therapy influence work-loss in RA patients? AB - OBJECTIVE: To compare work-loss in RA patients starting their first biologic with high vs moderate disease activity. METHODS: We identified all RA patients aged 20 63 years in the Swedish Biologics Register who started their first biologic 2007 09 with high disease activity (DAS28 >5.1; n = 868) or moderate disease activity (DAS28 3.2-5.1; n = 854). Work days lost, defined as sick leave and disability pension days from the Swedish Social Insurance Agency, were assessed over 5 years after first bio-start. We estimated between-group mean differences adjusted for age, sex, calendar year, education level, disease duration, comorbidities and work-loss the month before bio-start. RESULTS: During 5 years after anti-TNF start, mean monthly work days lost declined from 16.0 to 9.2 (42%; P < 0.001) in patients with high disease activity at baseline and from 12.0 to 7.2 (40%; P < 0.001) in patients with moderate disease activity, with no between-group difference (adjusted mean difference 0.81; 95% CI - 0.44, 2.05). Accumulated 5 year work-loss was, however, higher in the high activity group (724 vs 548 days; adjusted mean difference 70; 95% CI 20, 120), but after stratification on baseline disability pension status, no differences in accumulated work-loss were detected. CONCLUSION: Substantial work-loss was seen in both patients with high and patients with moderate disease activity at anti-TNF start, with a 5-year decline in mean monthly work days lost by ~40% in both groups and no between group difference. Accumulated work-loss over 5 years was higher in the high activity group, which may be explained by differences in baseline disability pension status. PMID- 26683197 TI - Transport and channel functions in EAATs: the missing link. PMID- 26683198 TI - Testing the Benefits of Neurofeedback on Selective Attention Measured Through Dichotic Listening. AB - The electrophysiological changes after a single session of neurofeedback training (?SMR/?Theta) and its effects on executive attention during a dichotic listening test with forced attentional procedures were measured in a sample of 20 healthy women. A pre-post moment test double blind design, with the inclusion of a group receiving sham neurofeedback, allowed for minimization of alien influences. The interaction of Moment * Group was significant, indicating an enhancement of SMR band after the real neurofeedback. The dichotic listening scores were correlated with the amplitude of Beta band in baseline conditions. The performance on the forced left attentional condition in dichotic listening was significantly improved and correlated positively with the post-training enhancement of the SMR band. The sham neurofeedback group also improved DL scores, so a clear affirmation about the benefits of neurofeedback training over cognitive performance could not be unambiguously established. It is concluded that the protocol showed a good independence and acceptable trainability in modifying the EEG results, but there was limited interpretability regarding cognitive outcomes. PMID- 26683199 TI - Canines are affected in 16-year-olds with molar-incisor hypomineralisation (MIH): an epidemiological study based on the Tromso study: "Fit Futures". AB - AIM: This was to determine the prevalence, distribution of affected teeth and severity of MIH in adolescents from Northern Norway. METHODS: It was part of a cross-sectional health survey Fit Futures including 16-year-olds from two neighbouring municipalities, Tromso and Balsfjord. RESULTS: The prevalence of MIH was 13.9% (110 of 794). The maxillary first permanent molars (FPMs) were 1.6 times more frequently affected than in the mandible (P < 0.001). The FPMs on the right side were 1.2 times more often affected than the FPMs on the left side (P = 0.038). The maxillary incisors were 2.5 times more often affected than the incisors in the mandible (P < 0.001). The proportions of participants whose canines and incisors were involved were 22.8 and 41.8%, respectively. Altogether 201 FPMs were affected; 54.0% of these had opacities only, 24.3% had posteruptive breakdown (PEB), 18.8% had atypical restorations, and 3.0% had been extracted due to MIH. The buccal surfaces were most often affected in FPMs. More severe lesions were found in the mandibular FPMs compared with the maxillary FPMs (P = 0.002). In the lower canines, only opacities were recorded, while in the upper jaw 13.0% of the affected canines showed PEBs. The distribution of MIH in the dentition was not symmetrical. CONCLUSION: The prevalence of MIH (13.9%) in the study population of 16-year-olds from Northern Norway is consistent with previous Scandinavian reports. The distribution pattern shows that one participant in four with MIH had at least one affected canine. Further studies are needed to describe the localisation of defects on the enamel surface and to relate these findings to enamel thickness and the duration of amelogenesis. PMID- 26683200 TI - Electrokinetic-Enhanced Remediation of Phenanthrene-Contaminated Soil Combined with Sphingomonas sp. GY2B and Biosurfactant. AB - Electrokinetic-microbial remediation (EMR) has emerged as a promising option for the removal of polycyclic aromatic hydrocarbons (PAHs) from contaminated soils. The aim of this study was to enhance degradation of phenanthrene (Phe) contaminated soils using EMR combined with biosurfactants. The electrokinetic (EK) remediation, combined with Phe-degrading Sphingomonas sp. GY2B, and biosurfactant obtained by fermentation of Pseudomonas sp. MZ01, degraded Phe in the soil with an efficiency of up to 65.1 % at the anode, 49.9 % at the cathode after 5 days of the treatment. The presence of biosurfactants, electricity, and a neutral electrolyte stimulated the growth of the degrading bacteria as shown by a rapid increase in microbial biomass with time. The electrical conductivity and pH changed little during the course of the treatment, which benefitted the growth of microorganisms and the remediation of Phe-contaminated soil. The EMR system with the addition of biosurfactant had the highest Phe removal, demonstrating the biosurfactant may enhance the bioavailability of Phe and the interaction with the microorganism. This study suggests that the EMR combined with biosurfactants can be used to enhance in situ bioremediation of PAH-contaminated soils. PMID- 26683201 TI - Modeling overdispersion heterogeneity in differential expression analysis using mixtures. AB - Next-generation sequencing technologies now constitute a method of choice to measure gene expression. Data to analyze are read counts, commonly modeled using negative binomial distributions. A relevant issue associated with this probabilistic framework is the reliable estimation of the overdispersion parameter, reinforced by the limited number of replicates generally observable for each gene. Many strategies have been proposed to estimate this parameter, but when differential analysis is the purpose, they often result in procedures based on plug-in estimates, and we show here that this discrepancy between the estimation framework and the testing framework can lead to uncontrolled type-I errors. Instead, we propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Three consistent statistical tests are developed for differential expression analysis. We show through a wide simulation study that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it reaches the nominal value for the type-I error, while keeping elevate discriminative power between differentially and not differentially expressed genes. The method is finally illustrated on prostate cancer RNA-Seq data. PMID- 26683202 TI - Deep sedation versus general anesthesia in percutaneous edge-to-edge mitral valve reconstruction using the MitraClip system. AB - BACKGROUND: Percutaneous edge-to-edge mitral valve reconstruction (PMVR) has emerged as a treatment option in patients with severe mitral regurgitation not considered suitable candidates for surgery. The majority of PMVR procedures are performed under general anesthesia (GA), although deep sedation (DS) appears to be an attractive alternative. We thus sought to assess the impact on intensive care unit (ICU) length of stay, efficacy, and safety of DS in comparison to GA in patients undergoing PMVR using the MitraClip((r)) system. METHODS: Sixty consecutive patients underwent PMVR procedures at two centers. The first 30 patients were treated by GA followed by 30 patients undergoing DS under different settings. The primary clinical endpoint was ICU length of stay. The primary efficacy endpoint included procedural success and procedural duration. The safety endpoint was defined as a composite of death, stroke, cardiogenic shock, moderate and severe bleeding as well as pneumonia. RESULTS: The ICU length of stay was significantly shorter in the DS group in comparison to GA patients (p = 0.001). The hospital length of stay did not differ following DS in comparison to GA (p = 0.96). Procedural success was high in both groups (100 versus 96.7 %, p = 0.34) at similar procedural duration time (p = 0.60). No difference between GA and DS was observed with respect to the occurrence of the combined safety endpoint (p = 0.47). CONCLUSIONS: In comparison to GA, DS reduces the ICU length of stay in PMVR without negative effects on safety and efficacy. Prospective randomized trials are needed to confirm these findings. PMID- 26683204 TI - Analysis of work ability and work-related physical activity of employees in a medium-sized business. AB - BACKGROUND: Work-related physical activity (PA) and work ability are of growing importance in modern working society. There is evidence for age- and job-related differences regarding PA and work ability. This study analyses work ability and work-related PA of employees in a medium-sized business regarding age and occupation. METHODS: The total sample consists of 148 employees (116 men-78.38% of the sample-and 32 women, accounting for 21.62%; mean age: 40.85 +/- 10.07 years). 100 subjects (67.57%) are white-collar workers (WC), and 48 (32.43%) are blue-collar workers (BC). Work ability is measured using the work ability index, and physical activity is obtained via the Global Physical Activity Questionnaire. RESULTS: Work ability shows significant differences regarding occupation (p = 0.001) but not regarding age. Further, significant differences are found for work related PA concerning occupation (p < 0.0001), but again not for age. Overall, more than half of all subjects meet the current guidelines for physical activity. CONCLUSION: Work ability is rated as good, yet, a special focus should lie on the promotion during early and late working life. Also, there is still a lack of evidence on the level of work-related PA. Considering work-related PA could add to meeting current activity recommendations. PMID- 26683203 TI - Hypoestoxide reduces neuroinflammation and alpha-synuclein accumulation in a mouse model of Parkinson's disease. AB - BACKGROUND: Deposition of alpha-synuclein and neuroinflammation are key pathological features of Parkinson's disease (PD). There is no cure for the disease; however, targeting the pathological features might be available to modulate the disease onset and progression. Hypoestoxide (HE) has been demonstrated as a NF-kappaB modulator, thereby acting as a potential anti inflammatory and anti-cancer drug. METHODS: In order to assess the effect of HE in a mouse model of PD, mThy1-alpha-syn transgenic mice received intraperitoneal (IP) injections of either vehicle or HE (5 mg/kg) daily for 4 weeks. RESULTS: Treatment of HE decreased microgliosis, astrogliosis, and pro-inflammatory cytokine gene expression in alpha-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the alpha-syn transgenic mice, and alpha-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-kappaB in the frontal cortex of alpha-syn transgenic mice were significantly reduced by HE administration. CONCLUSIONS: These results support the therapeutic potential of HE for PD and other alpha-synuclein-related diseases. PMID- 26683205 TI - Rhynchophorus palmarum in Disguise: Undescribed Polymorphism in the "Black" Palm Weevil. AB - During studies to adapt pheromone trapping of Rhynchophorus palmarum to the special coconut growing conditions at the Colombian Pacific coast, 152 atypically colored specimens were captured in a total collection of 53,802 of the normally completely black weevil. Five specimens had the typical coloration of Rhynchophorus ferrugineus, an invasive species recently introduced to Aruba and Curacao. A regional expansion of this invasion to the South American continent was feared and all atypical specimens were submitted to taxonomic analysis. Both conventional and molecular methods were employed. Conventional taxonomics confirmed the samples as belonging to R. palmarum but registered undescribed and species-atypical morphological variability in the subgular suture (wide vs. narrow), the ratio between intraocular distance and width of antennal scrobes (>0.35 vs. < 0.29) and the indentation of the mandibles (up to three mandibular teeth vs. bilobed). Molecular analysis placed all samples inspected, black and reddish alike, firmly within the R. palmarum group and the hypothesis of having inter-specific hybrids was rejected using co-dominant single sequence repeat markers with allelic specificity for both species. PMID- 26683207 TI - Temperature Dependence of Radiative and Nonradiative Rates from Time-Dependent Correlation Function Methods. AB - The temperature dependence of the rate constants in radiative and nonradiative decays from excited electronic states has been studied using a time-dependent correlation function approach in the framework of the adiabatic representation and the harmonic oscillator approximation. The present work analyzes the vibrational aspect of the processes, which gives rise to the temperature dependence, with the inclusion of mode-mixing, as well as of frequency change effects. The temperature dependence of the rate constants shows a contrasting nature, depending on whether the process has been addressed within the Franck Condon approximation or beyond it. The calculation of the Duschinsky matrix and the shift vector between the normal modes of the two states can be done in Cartesian and/or internal coordinates, depending on the flexibility of the investigated molecule. A new computational code has been developed to calculate the rates of intersystem crossing, internal conversion, and fluorescence for selected molecules as functions of temperature. PMID- 26683206 TI - The antioxidative effects of acidic-, alkalic-, and enzymatic-extractable mycelium zinc polysaccharides by Pleurotus djamor on liver and kidney of streptozocin-induced diabetic mice. AB - BACKGROUND: Edible mushrooms, especially the genus of Pleurotus, have been well studied for their nutrition as well as non-toxic medicinal properties. Recently, much attention has been paid to the therapeutic values of mushrooms in genus of Pleurotus with diabetes mellitus (DM), which was a complex metabolic disorder that induced by increased oxidative stress and characterized by hyperglycemia. However, scare attention has been paid to polysaccharides from P. djamor. Meanwhile, zinc is an essential trace element in the human body and it participates in various pathways of metabolism. Therefore, the objective of present study was aimed to evaluate the protective effects of the three extractable mycelium zinc polysaccharides (MZPS), including acidic-MZPS (Ac MZPS), alkalic-MZPS (Al-MZPS) and enzymatic-MZPS (En-MZPS), on the liver and kidneys in diabetic mice induced by streptozocin (STZ) aiming to better understand the possible hypoglycemic mechanisms and their health benefits. METHODS: The Ac-, Al-, and En-MZPS were extracted with hydrochloric acid (1 M), sodium hydroxide (1 M) and snailase (4 %) from P. djamor zinc-enriched mycelium, respectively. The diabetic mice were induced by injection of STZ. Besides the histopathological analyses of liver and kidney, the following biochemical analysis were processed to investigate the antioxidative effects, including activities of superoxide dismutase (SOD), GSH peroxide (GSH-Px) and catalase (CAT), and contents of malondialdehyde (MDA) in liver and kidney homogenate; activities of alamine aminotransferase (ALT) and aspertate aminotransferase (AST), and levels of urea nitrogen (BUN), creatinine (CRE), total cholesterol (TC), albumin (ALB), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) in serum. RESULTS: Results showed that the activities of SOD, GSH-Px and CAT were significantly increased, the MDA contents remarkably reduced, and the values of ALT, AST, BUN, CRE, TC, LDL-C and HDL-C observably mitigated in the liver, kidneys and serum of diabetic mice by these three polysaccharides treatment. Biochemical and histopathological analyses also showed that MZPS could alleviate liver and kidneys injury. CONCLUSION: These results demonstrated that Ac-, Al-, and En-MZPS possessed potent antioxidant activities, and could be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ. PMID- 26683208 TI - Systemic lupus erythematosus: lupus nephritis. AB - INTRODUCTION: Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the US. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of immunosuppressants in people with proliferative lupus nephritis? What are the effects of different immunosuppressants compared with each other in people with proliferative lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 448 studies. After deduplication and removal of conference abstracts, 120 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 53 studies and the further review of 67 full publications. Of the 67 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for 13 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 10 interventions based on the effectiveness and safety of immunosuppressants plus corticosteroids compared with corticosteroids alone, and immunosuppressants plus corticosteroids compared with each other in people with proliferative lupus nephritis (WHO grades III-V). PMID- 26683210 TI - Mn vacancy defects, grain boundaries, and A-phase stability of helimagnet MnSi. AB - Mn vacancy defect and grain size are shown to modify the magnetic phase diagram of MnSi significantly, especially near the critical regime of A-phase (skyrmion lattice) formation and the helimagnetic phase transition. Crystals grown using controlled nonstoichiometric initial precursors creates both grain boundaries and intrinsic Mn vacancy defect of various levels in MnSi. The results of combined transport, specific heat, and AC spin susceptibility measurements are compared for MnSi single crystal samples of various manganese deficiency levels and grain sizes. The finite-size effect and Mn vacancy level dependent helical phase transition temperature T(c) have been identified and verified. The stability of A phase in H-T phase space has been examined through AC spin susceptibility data analysis. PMID- 26683209 TI - Plasma levels of microRNA are altered with the development of shock in human sepsis: an observational study. AB - BACKGROUND: Endothelial dysfunction plays a critical role in the development of sepsis-related organ failure; however, the mechanisms that govern its development are not fully understood. Endothelial progenitor cells (EPCs) reduce vascular leak and organ failure in experimental sepsis while modulating plasma expression of microRNA (miRNA). MicroRNAs are small, noncoding segments of RNA that regulate gene expression and are known to modulate endothelial cell function and inflammatory signaling pathways. We hypothesized that miRNA may play an etiologic role in the endothelial dysfunction of sepsis and that their extracellular expression levels would be altered in those with shock. METHODS: Thirteen miRNAs were identified by literature search and analysis of the contents of human EPC derived exosomes using real-time PCR. Plasma samples were obtained from patients within 24 hours of their admission to ICUs with severe sepsis (n = 62) and from healthy controls (n = 32) and real-time PCR was used to measure the expression of the candidate miRNAs. The Wilcoxon rank sum test was used to compare expression levels of the 13 candidate miRNAs in septic patients with (n = 29) and without (n = 33) shock while logistic regression was used to determine the area under the curve for associations between miRNA expression and shock. Bioinformatic analyses using miRNA databases were performed to identify pathways and gene targets of differentially expressed miRNA with potential relevance to sepsis-related shock. RESULTS: MiRNA-34a expression was significantly increased in the group who developed shock (p = 0.03) while miR-15a and miR-27a expressions were significantly decreased in this group (p = 0.006 and 0.03, respectively). The combined expression of these three miRNAs predicted shock with an area under the curve of 0.78 (95 % CI 0.66-0.90). In silico analyses predict that these three miRNAs regulate genes involved in endothelial cell cycle, apoptosis, VEGF signaling, LPS-stimulated MAPK signaling, and nuclear factor kappa B signaling. CONCLUSIONS: The plasma levels of miRNA are altered in patients with severe sepsis complicated by shock and may offer prognostic value as well as insights into the mechanisms of endothelial dysfunction in sepsis. PMID- 26683211 TI - How the economic recession has changed the likelihood of reporting poor self rated health in Spain. AB - BACKGROUND: Between 2006 and 2011 self-rated health (SRH) (the subjective report of an individual's health status) actually improved in Spain despite its being in the grips of a serious economic recession. This study examines whether the likelihood of reporting poor health has changed because of the global financial crisis. It also attempts to estimate the differences between SRH and other self perceived measures of health among groups before and during the current economic crisis in Spain. METHODS: Cross-sectional population-based surveys were conducted in Spain (ENSE 2006 and ENSE 2011) and in Catalonia (ESCA 2006 and ESCA 2011) in 2006 and again in 2011. In this research work we have used random effects logistic models (dependent variable SRH 1 Poor, 0 Good) and exact matching and propensity score-matching. RESULTS: The results of the ENSE explanatory variables are the same in both 2006 and 2011. In other words, all diseases negatively affect SRH, whereas alcohol habits positively affect SRH and obesity is the only disease unrelated to SRH. ESCA explanatory variables' results show that in 2006 all diseases are significant and have large odds ratio (OR) and consequently those individuals suffering from any of these diseases are more likely to report poor health. In 2011 the same pattern follows with the exception of allergies, obesity, high cholesterol and hypertension, albeit they are not statistically significant. Drinking habits had a positive effect on SRH in 2006 and 2011, whereas smoking is considered as unrelated to SRH. The likelihood of reporting poor health in 2006 is added as a variable in with the logistic regression of 2011 and is not, in either the ENSE data or the ESCA data, significant. Furthermore, neither is it significant when controlling by age, gender, employment status or education. CONCLUSIONS: The results of our analysis show that the financial crisis did not alter the likelihood of reporting poor health in 2011. Therefore, there are no differences between our perceived health in either 2006 or in 2011. PMID- 26683212 TI - In vitro model systems to investigate bile salt export pump (BSEP) activity and drug interactions: A review. AB - The bile salt export pump protein (BSEP), expressed on the canalicular membranes of hepatocytes, is primarily responsible for the biliary excretion of bile salts. The inhibition of BSEP transport activity can lead to an increase in intracellular bile salt levels and liver injury. This review discusses the various in vitro assays currently available for assessing the effect of drugs or other chemical entities to modulate BSEP transport activity. BSEP transporter assays use one of the following platforms: Xenopus laevis oocytes; canalicular membrane vesicles (CMV); BSEP-expressed membrane vesicles; cell lines expressing BSEP; sandwich cultured hepatocytes (SCH); and hepatocytes in suspension. Two of these, BSEP-expressed insect membrane vesicles and sandwich cultured hepatocytes, are the most commonly used assays. BSEP membrane vesicles prepared from transfected insect cells are useful for assessing BSEP inhibition or substrate specificity and exploring mechanisms of BSEP-associated genetic diseases. This model can be applied in a high-throughput format for discovery-drug screening. However, experimental results from use of membrane vesicles may lack physiological relevance and the model does not allow for investigation of in situ metabolism in modulation of BSEP activity. Hepatocyte-based assays that use the SCH format provide results that are generally more physiologically relevant than membrane assays. The SCH model is useful in detailed studies of the biliary excretion of drugs and BSEP inhibition, but due to the complexity of SCH preparation, this model is used primarily for determining biliary clearance and BSEP inhibition in a limited number of compounds. The newly developed hepatocyte in suspension assay avoids many of the complexities of the SCH method. The use of pooled cryopreserved hepatocytes in suspension minimizes genetic variance and individual differences in BSEP activity and also provides the opportunity for higher throughput screening and cross-species comparisons. PMID- 26683213 TI - A Guide to Computational Tools and Design Strategies for Genome Editing Experiments in Zebrafish Using CRISPR/Cas9. AB - The development of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology for mainstream biotechnological use based on its discovery as an adaptive immune mechanism in bacteria has dramatically improved the ability of molecular biologists to modify genomes of model organisms. The zebrafish is highly amenable to applications of CRISPR/Cas9 for mutation generation and a variety of DNA insertions. Cas9 protein in complex with a guide RNA molecule recognizes where to cut the homologous DNA based on a short stretch of DNA termed the protospacer-adjacent motif (PAM). Rapid and efficient identification of target sites immediately preceding PAM sites, quantification of genomic occurrences of similar (off target) sites and predictions of cutting efficiency are some of the features where computational tools play critical roles in CRISPR/Cas9 applications. Given the rapid advent and development of this technology, it can be a challenge for researchers to remain up to date with all of the important technological developments in this field. We have contributed to the armamentarium of CRISPR/Cas9 bioinformatics tools and trained other researchers in the use of appropriate computational programs to develop suitable experimental strategies. Here we provide an in-depth guide on how to use CRISPR/Cas9 and other relevant computational tools at each step of a host of genome editing experimental strategies. We also provide detailed conceptual outlines of the steps involved in the design and execution of CRISPR/Cas9-based experimental strategies, such as generation of frameshift mutations, larger chromosomal deletions and inversions, homology-independent insertion of gene cassettes and homology-based knock-in of defined point mutations and larger gene constructs. PMID- 26683214 TI - Allophony of /j/ in Peninsular Spanish. AB - The phoneme /j/ in Spanish is known to have a wide range of phonetic realizations, even within a single dialect. Whereas the influence of different contextual factors in conditioning the allophony of /b d g/ has been the object of much recent acoustic investigation, somewhat surprisingly there are no comparable studies of the voiced palatal obstruent. We report on an acoustic investigation of this consonant in Peninsular Spanish. Both preceding context and stress appear to be relevant factors. We also find an effect of style, with more constriction in more formal styles. The presence of a word boundary also affects the degree of constriction, although to a lesser extent. Although we have identified several conditioning factors in the degree of constriction of this consonant, compared to /b d g/, there appears to be greater variability in a given context, including very constricted, stop-like realizations of /j/ in conversational styles even within the intervocalic context. Whereas our results largely confirm previous nonquantified description, they offer a more nuanced view of the continuum of the degree of constriction in the realization of this consonant and the factors that affect it, going beyond earlier views that postulated distinct allophones. PMID- 26683215 TI - Docosahexaenoic Acid and Its Role in G-Protein-Coupled Receptor 120 Activation in Children Affected by Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease in children and adults. Recently, therapeutic supplementation with docosahexaenoic acid (DHA) showed an anti-inflammatory and insulin-sensitizing effect in children with NAFLD. The anti-inflammatory effects of DHA depend on its ability to alter phospholipid composition of the cell membrane, to disrupt lipid rafts and to hamper the transcriptional activity of nuclear factor-x03BA;B that controls the expression of proinflammatory cytokines. These effects of DHA are due to the interaction with the G-protein-coupled receptor 120 (GRP120), a lipid-sensing receptor highly expressed in activated macrophages. In fact, DHA may activate GPR120 expression in macrophages causing anti-inflammatory effects, and insulin-sensitizing and antidiabetic effects in vivo. Recently, it has been shown that GPR120 is also expressed by the Kupffer cells of the liver. A diet low in n-3 polyunsaturated fatty acids, as well as the presence of genetic factors, may induce a reduction in the GRP120 signal and the activation of Kupffer cells and inflammation during NAFLD. Therefore, it is conceivable that DHA/GRP120 may play a key role in slowing the progression of liver damage in patients with NAFLD. PMID- 26683216 TI - Bis-Sulfonyl O,C,O-Chelated Metallylenes (Ge, Sn) as Adjustable Ligands for Iron and Tungsten Complexes. AB - The synthesis and characterization of an E2 CE2 bis-sulfonyl aryl pincer ligand and its efficiency for the stabilization of compounds containing low-valent Group 14 elements (Ge and Sn) are reported. Complexation reaction of these metallylenes with iron or tungsten complexes resulted in the modulation of the oxygen atoms of the sulfonyl groups implicated in the stabilization of the Group 14 elements, demonstrating the original adjustable character of the bis-sulfonyl O2 S-C-SO2 aryl pincer. PMID- 26683217 TI - A Chinese Immigrant Paradox? Low Coronary Heart Disease Incidence but Higher Short-Term Mortality in Western-Dwelling Chinese Immigrants: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Chinese form a large proportion of the immigrant population in Western countries. There is evidence that Chinese immigrants experience an increased risk of coronary heart disease (CHD) after immigration in part due to cultural habits and acculturation. This is the first systematic review and meta analysis that aims to examine the risk of CHD in people of Chinese ethnicity living in Western countries, in comparison with whites and another major immigrant group, South Asians. METHODS AND RESULTS: Literature on the incidence, mortality, and prognosis of CHD among Chinese living in Western countries was searched systematically in any language using 6 electronic databases up to December 2014. Based on the meta-analysis, Chinese had lower incidence of CHD compared with whites (odds ratio 0.29; 95% CI: 0.24-0.34) and South Asians (odds ratio 0.37; 95% CI: 0.24-0.57) but higher short-term mortality after first hospitalization for acute myocardial infarction compared with whites (odds ratio 1.34; 95% CI, 1.04-1.73) and South Asians (odds ratio 1.82; 95% 1.33-2.50). There was no significant difference between Chinese immigrants and whites in long-term outcomes (mortality and recurrent events) after acute myocardial infarction. CONCLUSIONS: These findings provide an important focus for resource planning to enhance early secondary prevention of CHD to improve short-term survival outcomes among Western-dwelling Chinese immigrants. PMID- 26683218 TI - Myocardial Fibrosis Quantified by Extracellular Volume Is Associated With Subsequent Hospitalization for Heart Failure, Death, or Both Across the Spectrum of Ejection Fraction and Heart Failure Stage. AB - BACKGROUND: Myocardial fibrosis (MF) in noninfarcted myocardium may be an interstitial disease pathway that confers vulnerability to hospitalization for heart failure, death, or both across the spectrum of heart failure and ejection fraction. Hospitalization for heart failure is an epidemic that is difficult to predict and prevent and requires potential therapeutic targets associated with outcomes. METHOD AND RESULTS: We quantified MF with cardiovascular magnetic resonance extracellular volume fraction (ECV) measures in 1172 consecutive patients without amyloidosis or hypertrophic or stress cardiomyopathy and assessed associations with outcomes using Cox regression. ECV ranged from 16.6% to 47.8%. Over a median of 1.7 years, 111 patients experienced events after cardiovascular magnetic resonance, 55 had hospitalization for heart failure events, and there were 74 deaths. ECV was more strongly associated with outcomes than "nonischemic" MF observed with late gadolinium enhancement, thus ECV quantified MF in multivariable models. Adjusting for age, sex, renal function, myocardial infarction size, ejection fraction, hospitalization status, and heart failure stage, higher ECV was associated with hospitalization for heart failure (hazard ratio 1.77; 95% CI 1.32 to 2.36 for every 5% increase in ECV), death (hazard ratio 1.87 95% CI 1.45 to 2.40) or both (hazard ratio 1.85, 95% CI 1.50 to 2.27). ECV improved classification of persons at risk and improved model discrimination for outcomes (eg, hospitalization for heart failure: continuous net reclassification improvement 0.33, 95% CI 0.05 to 0.66; P=0.02; 0.16, 95% CI 0.01 to 0.33; P=0.02; integrated discrimination improvement 0.037, 95% CI 0.008 to 0.073; P<0.01). CONCLUSION: MF measured by ECV is associated with hospitalization for heart failure, death, or both. MF may represent a principal phenotype of cardiac vulnerability that improves risk stratification. Because MF can be reversible, cells and enzymes regulating collagen could be potential therapeutic targets. PMID- 26683219 TI - Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China. AB - BACKGROUND: Conflicting evidence exists regarding whether reduced estimated glomerular filtration rate (eGFR) and proteinuria are independent risk factors for stroke and its subtypes in hypertensive patients. This study investigated the association of these renal measures with first incident stroke in adults under treatment for hypertension in China. METHODS AND RESULTS: The study included 19 599 adults aged 45 to 75 years who participated in the China Stroke Primary Prevention Trial. Baseline eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Proteinuria was assessed by qualitative dipstick urinalysis and in a subset by the quantitative albumin creatinine ratio method. Cox regression analysis was used to examine the effects of eGFR and proteinuria on the risk of first incident stroke. During a median of 4.5 years of follow-up, a total of 585 first strokes (472 ischemic strokes) were identified. Compared to participants without proteinuria, participants with proteinuria (trace or more by dipstick) had a 35% increased risk of first stroke: the adjusted hazard ratio (HR) (95% CI) was 1.35 (1.09-1.66, P=0.005). The results were robust in subgroup analyses. In a subset with data on proteinuria measured by quantitative albumin-creatinine ratio, a similar association was found. In both independent and combined analyses with proteinuria, eGFR was not significantly associated with stroke. CONCLUSIONS: In adults under treatment for hypertension in China, baseline proteinuria measured by dipstick or quantitative albumin-creatinine ratio, but not reduced eGFR, was found to be an independent risk factor for first incident stroke and ischemic stroke. PMID- 26683221 TI - Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs. AB - Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability. PMID- 26683220 TI - PARKIN Inactivation Links Parkinson's Disease to Melanoma. AB - BACKGROUND: Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression. METHODS: An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided. RESULTS: Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation. CONCLUSION: Our results show an important role for PARK2 as a tumor suppressor both in melanoma predisposition and progression, which could explain the epidemiological association of these diseases. PMID- 26683222 TI - Obesity and Functioning Among Individuals with Chronic Obstructive Pulmonary Disease (COPD). AB - In COPD, body composition studies have focused primarily on low BMI. We examined obesity (BMI >= 30 kg/m(2)) as a risk factor for poor function and longitudinal functional decline. Data from a longitudinal cohort of adults with COPD (n = 1096) and an age- and sex-matched comparison group collected in two in-person visits ~49 months apart were analyzed. Two measures of functioning were examined: six-minute walk distance (6MWD) and Short Physical Performance Battery (SPPB). Multivariate regression analyses examined relationships of obesity with functioning. Secondary analyses stratified by GOLD classification (GOLD-0/1, GOLD 2, GOLD-3/4). Obesity (53% of COPD cohort) was associated cross-sectionally with 6MWD and SPPB in COPD, and only with 6MWD in the comparison group. Obesity predicted significant functional decline in 6MWD for individuals with COPD (odds ratio (OR) for decline [95% CI] 1.8 [1.1, 2.9]), but not the comparison group. Secondary analyses revealed that the risk of decline was significant only in those with more severe COPD (GOLD 3/4, OR = 2.3 [1.0, 5.4]). Obesity was highly prevalent and was associated with poor function concurrently and with subsequent decline in 6MWD in COPD. Obesity in COPD should be considered a risk not only for more co-morbidities and greater health care use, but also for functional decline. PMID- 26683223 TI - Experimental Evidence of the Origin of Nanophase Separation in Low Hole-Doped Colossal Magnetoresistant Manganites. AB - While being key to understanding their intriguing physical properties, the origin of nanophase separation in manganites and other strongly correlated materials is still unclear. Here, experimental evidence is offered for the origin of the controverted phase separation mechanism in the representative La1-xCaxMnO3 system. For low hole densities, direct evidence of Mn(4+) holes localization around Ca(2+) ions is experimentally provided by means of aberration-corrected scanning transmission electron microscopy combined with electron energy loss spectroscopy. These localized holes give rise to the segregated nanoclusters, within which double exchange hopping between Mn(3+) and Mn(4+) remains restricted, accounting for the insulating character of perovskites with low hole density. This localization is explained in terms of a simple model in which Mn(4+) holes are bound to substitutional divalent Ca(2+) ions. PMID- 26683224 TI - Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells. AB - Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer. PMID- 26683225 TI - Identification of TIM3 2'-fluoro oligonucleotide aptamer by HT-SELEX for cancer immunotherapy. AB - TIM3 belongs to a family of receptors that are involved in T-cell exhaustion and Treg functions. The development of new therapeutic agents to block this type of receptors is opening a new avenue in cancer immunotherapy. There are currently several clinical trials ongoing to combine different immune-checkpoint blockades to improve the outcome of cancer patients. Among these combinations we should underline PD1:PDL1 axis and TIM3 blockade, which have shown very promising results in preclinical settings. Most of these types of therapeutic agents are protein cell-derived products, which, although broadly used in clinical settings, are still subject to important limitations. In this work we identify by HT-SELEX TIM3 non-antigenic oligonucleotide aptamers (TIM3Apt) that bind with high affinity and specificity to the extracellular motives of TIM3 on the cell surface. The TIM3Apt1 in its monomeric form displays a potent antagonist capacity on TIM3-expressing lymphocytes, determining the increase of IFN-gamma secretion. In colon carcinoma tumor-bearing mice, the combinatorial treatment of TIM3Apt1 and PDL1-antibody blockade is synergistic with a remarkable antitumor effect. Immunotherapeutic aptamers could represent an attractive alternative to monoclonal antibodies, as they exhibit important advantages; namely, lower antigenicity, being chemically synthesized agents with a lower price of manufacture, providing higher malleability, and antidote availability. PMID- 26683226 TI - MTDH is an oncogene in multiple myeloma, which is suppressed by Bortezomib treatment. AB - Metadherin (MTDH) is identified as an oncogene in multiple cancers including breast cancer, bladder cancer and endometrial cancer. However, the function of MTDH in multiple myeloma (MM) is still unexplored. In this study, we disclose that MTDH is an oncogene in MM. This is characterized by an elevation mRNA level of MTDH and chromosomal gain of MTDH locus in MM cells compared to normal samples. Moreover, MTDH expression significantly increased in MMSET translocation (MS) subgroup, one of the high-risk subgroups in MM, and was significantly correlated with MM patients' poor outcomes in Total Therapy 2 (TT2) cohort. Further knockdown of MTDH expression by shRNA in MM cells induced cell apoptosis, inhibited MM cells growth in vitro and decreased xenograft tumor formation in vivo. Interestingly, opposite to TT2, MM patients with high-MTDH expression showed favorable survival outcomes in the TT3 cohort, while Bortezomib treatment was the major difference between TT2 and TT3 cohort. Furthermore we proved that Bortezomib suppressed pre- and post-transcription levels of MTDH expression of MM cells in vitro and in vivo. Finally, our studies demonstrated that MTDH is a transcriptional gene of MMSET/NFkappaB /MYC signaling in MM cells, which is inhibited by Bortezomib treatment. PMID- 26683227 TI - SHIP represses lung inflammation and inhibits mammary tumor metastasis in BALB/c mice. AB - SH2-containing-inositol-5'-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol-3-kinase pathway in hematopoietic cells and limits the development of leukemias and lymphomas. The potential role of SHIP in solid tumor development and metastasis remains unknown. While SHIP restricts the aberrant development of myeloid cells in C57BL/6 mice, there are conflicting reports regarding the effect of SHIP deletion in BALB/c mice with important consequences for determining the influence of SHIP in different model tumor systems. We generated SHIP-/- BALB/c mice and challenged them with syngeneic non-metastatic 67NR or metastatic 4T1 mammary tumors. We demonstrate that SHIP restricts the development, alternative-activation, and immunosuppressive function of myeloid cells in tumor-free and tumor-bearing BALB/c mice. Tumor-free SHIP-/- BALB/c mice exhibited pulmonary inflammation, myeloid hyperplasia, and M2-polarized macrophages and this phenotype was greatly exacerbated by 4T1, but not 67NR, tumors. 4T1-bearing SHIP-/- mice rapidly lost weight and died from necrohemorrhagic inflammatory pulmonary disease, characterized by massive infiltration of pulmonary macrophages and myeloid-derived suppressor cells that were more M2-polarized and immunosuppressive than wild-type cells. Importantly, while SHIP loss did not affect primary tumor growth, 4T1-bearing SHIP-/- mice had 7.5-fold more metastatic tumor cells in their lungs than wild-type mice, consistent with the influence of immunosuppressive myeloid cells on metastatic growth. Our findings identify the hematopoietic cell-restricted protein SHIP as an intriguing target to influence the development of solid tumor metastases, and support development of SHIP agonists to prevent the accumulation of immunosuppressive myeloid cells and tumor metastases in the lungs to improve treatment of metastatic breast cancer. PMID- 26683228 TI - Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. AB - Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors), supporting its role as a novel driver mutation in UM. PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ, consistent with PLCB4 being the canonical downstream target of the former gene products. Taken together these data suggest that the PLCB4 hotspot mutation is similarly a gain-of-function mutation leading to activation of the same signaling pathway, promoting UM tumorigenesis. PMID- 26683229 TI - How anxiety induces verbal hallucinations. AB - Verbal hallucinations are often associated with pronounced feelings of anxiety, and it has also been suggested that anxiety somehow triggers them. In this paper, we offer a phenomenological or 'personal-level' account of how it does so. We show how anxious anticipation of one's own thought contents can generate an experience of their being 'alien'. It does so by making an experience of thinking more like one of perceiving, resulting in an unfamiliar kind of intentional state. This accounts for a substantial subset of verbal hallucinations, which are experienced as falling within one's psychological boundaries and lacking in auditory qualities. PMID- 26683230 TI - Response to Comment on "Diminishing Returns or Compounding Benefits of Air Pollution Control? The Case of NO(x) and Ozone". PMID- 26683231 TI - Clock-Talk: Interactions between Central and Peripheral Circadian Oscillators in Mammals. AB - In mammals, including humans, nearly all physiological processes are subject to daily oscillations that are governed by a circadian timing system with a complex hierarchical structure. The central pacemaker, residing in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus, is synchronized daily by photic cues transmitted from the retina to SCN neurons via the retinohypothalamic tract. In turn, the SCN must establish phase coherence between self-sustained and cell autonomous oscillators present in most peripheral cell types. The synchronization signals (Zeitgebers) can be controlled more or less directly by the SCN. In mice and rats, feeding-fasting rhythms, which are driven by the SCN through rest activity cycles, are the most potent Zeitgebers for the circadian oscillators of peripheral organs. Signaling through the glucocorticoid receptor and the serum response factor also participate in the phase entrainment of peripheral clocks, and these two pathways are controlled by the SCN independently of feeding-fasting rhythms. Body temperature rhythms, governed by the SCN directly and indirectly through rest-activity cycles, are perhaps the most surprising cues for peripheral oscillators. Although the molecular makeup of circadian oscillators is nearly identical in all cells, these oscillators are used for different purposes in the SCN and in peripheral organs. PMID- 26683232 TI - Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle. AB - Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 +/- 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues. PMID- 26683233 TI - Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. AB - This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings. PMID- 26683235 TI - What can evolutionary theory tell us about chronic pain? PMID- 26683236 TI - Sleep problems and pain: a longitudinal cohort study in emerging adults. AB - Sleep and pain are thought to be bidirectional related on a daily basis in adolescents with chronic pain complaints. In addition, sleep problems have been shown to predict the long-term onset of musculoskeletal pain in middle-aged adults. Yet, the long-term effects of sleep problems on pain duration and different types of pain severity in emerging adults (age: 18-25) are unknown. This study investigated the cross-sectional and longitudinal relationship between sleep problems and chronic pain, and musculoskeletal pain, headache, and abdominal pain severity in a general population of emerging adults. We studied whether these relationships were moderated by sex and whether symptoms of anxiety and depression, fatigue, or physical inactivity mediated these effects. Data of participants from the longitudinal Dutch TRacking Adolescents' Individual Lives Survey were used. Follow-up data were collected in 1753 participants who participated in the fourth (N = 1668, mean age: 19.0 years [SD = 0.6]) and/or fifth (N = 1501, mean age: 22.3 years [SD = 0.6]) assessment wave. Autoregressive cross-lagged models were used for analyses. Sleep problems were associated with chronic pain, musculoskeletal pain, headache and abdominal pain severity, and predicted chronic pain and an increase in musculoskeletal pain severity at 3 years of follow-up. This prospective effect was stronger in females than in males and was mediated by fatigue but not by symptoms of anxiety and depression or physical inactivity. Only abdominal pain had a small long-term effect on sleep problems. Our results suggest that sleep problems may be an additional target for treatment in female emerging adults with musculoskeletal pain complaints. PMID- 26683234 TI - Differences in demographic, clinical, and symptom characteristics and quality of life outcomes among oncology patients with different types of pain. AB - The purposes of this study, in oncology outpatients receiving chemotherapy (n = 926), were to: describe the occurrence of different types of pain (ie, no pain, only noncancer pain [NCP], only cancer pain [CP], or both CP and NCP) and evaluate for differences in demographic, clinical, and symptom characteristics, and quality of life (QOL) among the 4 groups. Patients completed self-report questionnaires on demographic and symptom characteristics and QOL. Patients who had pain were asked to indicate if it was or was not related to their cancer or its treatment. Medical records were reviewed for information on cancer and its treatments. In this study, 72.5% of the patients reported pain. Of the 671 who reported pain, 21.5% reported only NCP, 37.0% only CP, and 41.5% both CP and NCP. Across the 3 pain groups, worst pain scores were in the moderate to severe range. Compared with the no pain group, patients with both CP and NCP were significantly younger, more likely to be female, have a higher level of comorbidity, and a poorer functional status. In addition, these patients reported: higher levels of depression, anxiety, fatigue, and sleep disturbance; lower levels of energy and attentional function; and poorer QOL. Patients with only NCP were significantly older than the other 3 groups. The most common comorbidities in the NCP group were back pain, hypertension, osteoarthritis, and depression. Unrelieved CP and NCP continue to be significant problems. Oncology outpatients need to be assessed for both CP and NCP conditions. PMID- 26683238 TI - Chronic pain disorders in HIV primary care: clinical characteristics and association with healthcare utilization. AB - Chronic pain is common in HIV, but incompletely characterized, including its underlying etiologies, its effect on healthcare utilization, and the characteristics of affected patients in the HIV primary care setting. These data are needed to design and justify appropriate clinic-based pain management services. Using a clinical data warehouse, we analyzed one year of data from 638 patients receiving standard-of-care antiretroviral therapy in a large primary care HIV clinic, located in the Harlem neighborhood of New York City. We found that 40% of patients carried one or more chronic pain diagnoses. The most common diagnoses were degenerative musculoskeletal disorders (eg, degenerative spinal disease and osteoarthritis), followed by neuropathic pain and headache disorders. Many patients (16%) had multiple chronic pain diagnoses. Women, older patients, and patients with greater burdens of medical illness, and psychiatric and substance use comorbidities were disproportionately represented among those with chronic pain diagnoses. Controlling for overall health status, HIV patients with chronic pain had greater healthcare utilization including emergency department visits and radiology procedures. In summary, our study demonstrates the high prevalence of chronic pain disorders in the primary care HIV clinic. Colocated interventions for chronic pain in this setting should not only focus on musculoskeletal pain but also account for complex multifaceted pain syndromes, and address the unique biopsychosocial features of this population. Furthermore, because chronic pain is prevalent in HIV and associated with increased healthcare utilization, developing clinic-based pain management programs could be cost effective. PMID- 26683237 TI - Ensuring transparency and minimization of methodologic bias in preclinical pain research: PPRECISE considerations. AB - There is growing concern about lack of scientific rigor and transparent reporting across many preclinical fields of biological research. Poor experimental design and lack of transparent reporting can result in conscious or unconscious experimental bias, producing results that are not replicable. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration sponsored a consensus meeting of the Preclinical Pain Research Consortium for Investigating Safety and Efficacy (PPRECISE) Working Group. International participants from universities, funding agencies, government agencies, industry, and a patient advocacy organization attended. Reduction of publication bias, increasing the ability of others to faithfully repeat experimental methods, and increased transparency of data reporting were specifically discussed. Parameters deemed essential to increase confidence in the published literature were clear, specific reporting of an a priori hypothesis and definition of primary outcome measure. Power calculations and whether measurement of minimal meaningful effect size to determine these should be a core component of the preclinical research effort provoked considerable discussion, with many but not all agreeing. Greater transparency of reporting should be driven by scientists, journal editors, reviewers, and grant funders. The conduct of high quality science that is fully reported should not preclude novelty and innovation in preclinical pain research, and indeed, any efforts that curtail such innovation would be misguided. We believe that to achieve the goal of finding effective new treatments for patients with pain, the pain field needs to deal with these challenging issues. PMID- 26683239 TI - Development of interventions for the secondary prevention of Alzheimer's dementia: the European Prevention of Alzheimer's Dementia (EPAD) project. AB - Alzheimer's dementia affects more than 40 million people worldwide with substantial increases in prevalence anticipated. Interventions that either modify risk or reduce the development of early disease could delay the onset of dementia or reduce the rate of cognitive and functional decline. The European Prevention of Alzheimer's Dementia (EPAD) is a public-private consortium, funded by the Innovative Medicines Initiative, designed to increase the likelihood of successful development of new treatments for the secondary prevention of Alzheimer's dementia. EPAD will help with testing of different agents in this pre dementia population through four components: improvement of access to existing cohorts and registries, development of the EPAD Registry of approximately 24,000 people who might be at increased risk of developing Alzheimer's dementia, establishment of the EPAD Longitudinal Cohort Study of 6000 people at any one time, and establishment of an adaptive, proof-of-concept trial including 1500 participants at any given time. The need for EPAD and its key design elements are described, and we discuss EPAD in relation to similar projects in progress. These parallel efforts reflect the need for a coordinated, worldwide battle against dementia, in which EPAD will play a crucial role. PMID- 26683240 TI - Diabetes and Frailty: Two Converging Conditions? AB - Diabetes mellitus is a disabling, chronic cardiovascular and medical disease with a tremendous health, social and economic burden in our ageing communities. It has a prevalence of 10% to 30% in people older than 65 years of age, and more than half of all subjects with diabetes in the United States are older than 60 years of age. The main impact of diabetes in older adults stems from its effect on function, both physical and cognitive, that finally impairs their quality of life, although the impact on survival is modest. Frailty has emerged during the past 2 decades as the most powerful predictor of disability and other adverse outcomes, including mortality, disability and institutionalization in older adults. In this article we explore the relationship between diabetes and frailty, and we recognize that they are intimately related chronic medical conditions that result in huge societal and personal health burdens. PMID- 26683242 TI - Intrathecal administration of colistin for meningitis due to New Delhi metallo beta-lactamase 1(NDM-1)-producing Klebsiella pneumoniae. AB - Infection by bacteria carrying New Delhi metallo-beta-lactamase 1 (NDM-1) is becoming a global health problem. We report a case of meningitis caused by NDM-1 producing Klebsiella pneumoniae, for which intrathecal administration of colistin was curative. A previously healthy 38-year-old Japanese man, who lived in Hyderabad, India, suddenly collapsed and was brought to a local hospital. He was diagnosed with subarachnoid hemorrhage and underwent emergency surgery which included partial skull removal. Approximately 1 month after surgery, he was repatriated to Japan and was admitted to our institution with information that he had been treated for multi-drug resistant Acinetobacter infection with colistin. A week after admission, he developed aspiration pneumonia due to NDM-1-producing K. pneumoniae, which was successfully treated by intravenous (IV) administration of colistin. Subsequently, he underwent a surgical procedure to repair his skull defect. He developed high-grade fever and altered mental status on postoperative day 2. NDM-1-producing K. pneumoniae was identified in the cerebrospinal fluid, establishing the diagnosis of meningitis. Although IV colistin was only partially effective, intrathecal colistin (10 mg daily by lumbar puncture for 14 days) successfully eradicated the meningitis. Because of economic globalization, NDM-1 producing bacteria may be brought to Japan by those who are repatriated after sustaining critical illnesses and being treated in foreign countries. This report may provide useful information on the treatment of central nervous system infection by NDM-1-producing bacteria. PMID- 26683241 TI - Testing the generality of above-ground biomass allometry across plant functional types at the continent scale. AB - Accurate ground-based estimation of the carbon stored in terrestrial ecosystems is critical to quantifying the global carbon budget. Allometric models provide cost-effective methods for biomass prediction. But do such models vary with ecoregion or plant functional type? We compiled 15 054 measurements of individual tree or shrub biomass from across Australia to examine the generality of allometric models for above-ground biomass prediction. This provided a robust case study because Australia includes ecoregions ranging from arid shrublands to tropical rainforests, and has a rich history of biomass research, particularly in planted forests. Regardless of ecoregion, for five broad categories of plant functional type (shrubs; multistemmed trees; trees of the genus Eucalyptus and closely related genera; other trees of high wood density; and other trees of low wood density), relationships between biomass and stem diameter were generic. Simple power-law models explained 84-95% of the variation in biomass, with little improvement in model performance when other plant variables (height, bole wood density), or site characteristics (climate, age, management) were included. Predictions of stand-based biomass from allometric models of varying levels of generalization (species-specific, plant functional type) were validated using whole-plot harvest data from 17 contrasting stands (range: 9-356 Mg ha(-1) ). Losses in efficiency of prediction were <1% if generalized models were used in place of species-specific models. Furthermore, application of generalized multispecies models did not introduce significant bias in biomass prediction in 92% of the 53 species tested. Further, overall efficiency of stand-level biomass prediction was 99%, with a mean absolute prediction error of only 13%. Hence, for cost-effective prediction of biomass across a wide range of stands, we recommend use of generic allometric models based on plant functional types. Development of new species-specific models is only warranted when gains in accuracy of stand based predictions are relatively high (e.g. high-value monocultures). PMID- 26683243 TI - Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection. AB - BACKGROUND: Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS: We conducted a retrospective quasi experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS: We identified a total of 308 cases of BSI from January to December, 2012 (pre intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS: An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients. PMID- 26683244 TI - A first case of isolation of Kerstersia gyiorum from urinary tract. AB - An 82-year-old man with percutaneous nephrostomy presented to our Hospital with dysuria for one day. The patient's percutaneous nephrostomy tube was exchanged, with about 20 mL of creamy purulent urine being collected. Direct smear of the urine specimen showed polymorphonuclear leukocytes and small Gram-negative bacilli, some of which had undergone phagocytosis. This organism was identified as Kerstersia gyiorum using 16S ribosomal RNA gene analysis. He was successfully recovered with exchange of his percutaneous nephrostomy tube and fluoroquinolone internal use treatment. This is the first case report of urinary tract infection due to K. gyiorum. PMID- 26683245 TI - Epidemiology of invasive fungal infections after liver transplantation and the risk factors of late-onset invasive aspergillosis. AB - Invasive fungal infection (IFI) in liver transplant recipients is associated with poor outcomes. Targeted antifungal prophylaxis is recommended for high-risk populations; however, the epidemiology of IFI has changed, and the risk criteria remain unclear. In addition, the risk factors for late-onset invasive aspergillosis (IA) have not been fully characterized. We examined 279 recipients over 16 years of age to uncover their IFI epidemiology, clinical characteristics and outcomes. In addition, a case-control study was performed to identify the risk factors of late-onset IA. Of the 279 recipients, 96.1% underwent living donor liver transplantation. Antifungal prophylaxis was administered to 80.6% of the recipients. IFI occurred in 15 patients, among which 8 cases were early-onset (<=90 days after liver transplantation) and 7 cases were late-onset (>90 days after liver transplantation). Five of the late-onset cases were invasive pulmonary aspergillosis, and 2 were fungemia cases. The mortality rate of late onset IA was 80.0%. According to a multivariate analysis, steroid use before liver transplantation, bloodstream infection within 90 days after liver transplantation and reoperation within 90 days after liver transplantation were significant risk factors for late-onset IA after liver transplantation. The prevalence of IFI was low in our population given that over 80% of liver recipients received antifungal prophylaxis. The prognosis of late-onset IA remains poor, and predictors associated with late-onset IA, such as steroid use before liver transplantation, bloodstream infection and reoperation after liver transplantation, may help clinicians to optimize prevention measures for these devastating infections. PMID- 26683246 TI - Applying the Longitudinal Model from Item Response Theory to Assess Health Related Quality of Life in the PRODIGE 4/ACCORD 11 Randomized Trial. AB - INTRODUCTION: A new longitudinal statistical approach was compared to the classical methods currently used to analyze health-related quality-of-life (HRQoL) data. The comparison was made using data in patients with metastatic pancreatic cancer. METHODS: Three hundred forty-two patients from the PRODIGE4/ACCORD 11 study were randomly assigned to FOLFIRINOX versus gemcitabine regimens. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The classical analysis uses a linear mixed model (LMM), considering an HRQoL score as a good representation of the true value of the HRQoL, following EORTC recommendations. In contrast, built on the item response theory (IRT), our approach considered HRQoL as a latent variable directly estimated from the raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (longitudinal partial credit model [LPCM]), thereby modeling the latent trait as a function of time and other covariates. RESULTS: Both models gave the same conclusions on 11 of 15 HRQoL dimensions. HRQoL evolution was similar between the 2 treatment arms, except for the symptoms of pain. Indeed, regarding the LPCM, pain perception was significantly less important in the FOLFIRINOX arm than in the gemcitabine arm. For most of the scales, HRQoL changes over time, and no difference was found between treatments in terms of HRQoL. DISCUSSION: The use of LMM to study the HRQoL score does not seem appropriate. It is an easy-to-use model, but the basic statistical assumptions do not check. Our IRT model may be more complex but shows the same qualities and gives similar results. It has the additional advantage of being more precise and suitable because of its direct use of raw data. PMID- 26683247 TI - The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference. AB - Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. PMID- 26683248 TI - Words, rules, and mechanisms of language acquisition. AB - We review recent artificial language learning studies, especially those following Endress and Bonatti (Endress AD, Bonatti LL. Rapid learning of syllable classes from a perceptually continuous speech stream. Cognition 2007, 105:247-299), suggesting that humans can deploy a variety of learning mechanisms to acquire artificial languages. Several experiments provide evidence for multiple learning mechanisms that can be deployed in fluent speech: one mechanism encodes the positions of syllables within words and can be used to extract generalization, while the other registers co-occurrence statistics of syllables and can be used to break a continuum into its components. We review dissociations between these mechanisms and their potential role in language acquisition. We then turn to recent criticisms of the multiple mechanisms hypothesis and show that they are inconsistent with the available data. Our results suggest that artificial and natural language learning is best understood by dissecting the underlying specialized learning abilities, and that these data provide a rare opportunity to link important language phenomena to basic psychological mechanisms. For further resources related to this article, please visit the WIREs website. PMID- 26683249 TI - Preoperative management of factor XI deficiency with therapeutic plasma exchange: A case report and literature review. AB - : Patients with factor XI deficiency may have bleeding complications during surgery. Because bleeding severity and factor levels correlate poorly, factor replacement needs to be personalized based on bleeding history and type of procedure. We report a 65-year-old male with factor XI deficiency (7 IU dL-1 ) who presented before scheduled hip arthroplasty. He had a history of total hip arthroplasty complicated by bleeding, delayed healing and prosthesis removal, despite receiving prophylactic treatment with plasma infusion. For the current surgery a factor XI >=50 IU dL-1 level was targeted. The calculated plasma infusion needed to achieve this goal was 3100 mL (14 U). Because of concerns about circulatory overload and inability to achieve target by simple infusion, prophylactic treatment with therapeutic plasma exchange (TPE) was requested. TPE was performed the morning before the surgery, using 100% plasma as replacement fluid (3912 mL of plasma), and a positive fluid balance of 631 mL. Factor XI activity level was 51 IU dL-1 immediately post TPE. The patient received daily infusions of 3 U (~ 660 mL) of plasma to maintain a factor XI level of 30 IU dL-1 until post-operative day 7. Aminocaproic acid was given during the surgery and until post-operative day 10. There were no bleeding or thrombotic complications. CONCLUSION: TPE was effective in increasing factor XI levels; it was well tolerated and did not result in circulatory overload. TPE can be considered when therapeutic factor levels cannot be achieved by simple plasma infusion, or when circulatory overload is a concern. J. Clin. Apheresis 31:579-583, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26683250 TI - Progress in Dual Diagnosis Research: Innovation and Controlled Trials. PMID- 26683251 TI - Psychological Outcomes and Medical Morbidity of Patients With Bipolar Disorder and Co-Occurring Alcohol Use Disorder. AB - OBJECTIVE: Patients with bipolar disorder are at a high risk for comorbid alcohol use disorder, and both disorders are associated with poor outcomes and multiple morbidities. This study aimed to explore not only the psychosocial functioning and psychopathological outcomes but also the medical morbidity of patients with bipolar disorder with and without alcohol use disorder. METHODS: Outpatients with bipolar I disorder (DSM-IV) were recruited from a psychiatric teaching hospital in Taiwan (N = 393). Data on psychiatric symptoms, psychosocial functioning, and physical health were obtained through interviews with patients and collaterals, patient self-report, and medical record reviews. RESULTS: Participants had a mean age of 41.1 years (SD = 11.9) and were mostly female (n = 255, 64.9%). Fewer than 10% (n = 34, 8.7%) met criteria for alcohol use disorder, and these participants were more likely to be male, to smoke, and to have a history of rapid cycling, higher mean body mass index, and higher incidences of gastrointestinal and hepatobiliary morbidities. A multiple logistic regression analysis revealed that patients with, versus those without, alcohol use disorder were more prone to gastrointestinal diseases (adjusted OR = 4.25, 95% CI [1.44-12.53], p <.01), hepatobiliary diseases (adjusted OR = 3.14, 95% CI [1.20-8.25], p <.025), and history of rapid cycling (adjusted OR = 2.53, 95% CI [0.91-7.01], p <.075). CONCLUSIONS: Comorbid alcohol use disorders may have a stronger impact on physical health than on psychosocial or psychopathological outcomes of patients with bipolar disorder. PMID- 26683252 TI - Exercise and Counseling for Smoking Cessation in Smokers With Depressive Symptoms: A Randomized Controlled Pilot Trial. AB - OBJECTIVE: Despite various strategies to help smokers with depressive disorders to quit, the smoking relapse rate remains high. The purpose of this pilot study was to estimate the effects of adding an exercise and counseling intervention to standard smoking cessation treatment for smokers with depressive disorders. We hypothesized that the exercise and counseling intervention would lead to improved abstinence, reduced depressive symptoms, and increased physical activity. METHODS: Seventy smokers with current depressive disorders were randomly assigned to standard smoking cessation treatment plus exercise and counseling (n = 35) or standard treatment plus a time-to-contact control intervention on health education (n = 35). Both programs involved 10 sessions over 8 weeks. The primary outcome was continuous abstinence since the quit date and was measured at week 8 (end of the intervention) and again at 12-, 24-, and 52-week follow-ups. RESULTS: Nearly 60% of participants were female (n = 41), 38 (52.3%) were single, 37 (52.9%) had education beyond high school, and 32 (45.7%) met criteria for major depressive disorder or dysthymia. Participants in the two treatment conditions differed at baseline only in marital status (chi(2) = 4.28, df = 1, p =.04); and smoking abstinence self-efficacy, t(66) = -2.04, p =.04). The dropout rate did not differ significantly between groups and participants attended 82% and 75% of the intervention and control sessions, respectively. Intention-to-treat analysis showed that, at 12 weeks after the beginning of the intervention, continuous abstinence did not vary significantly between the intervention and control groups: 48.5% versus 28.5%, respectively, ORadj = 0.40, 95% CI [0.12-1.29], p =.12. There were no group differences in depressive symptoms, but the intervention group did outperform the control group on the 6-minute walking test (Mint = 624.84, SD = 8.17, vs. Mcon = 594.13, SD = 8.96, p =.015) and perceived physical control (Mint = 2.84, SD = 0.16, vs. Mcon = 2.27, SD = 0.18, p =.028). The sample was not large enough to ensure adequate statistical power. CONCLUSIONS: This finding, while preliminary, suggests that an exercise and counseling intervention may yield better results than health education in improving smoking abstinence. This study is registered at www.clinincaltrials.gov under # NCT01401569. PMID- 26683254 TI - The Effect of Haptic Support Systems on Driver Performance: A Literature Survey. AB - A large number of haptic driver support systems have been described in the scientific literature. However, there is little consensus regarding the design, evaluation methods, and effectiveness of these systems. This literature survey aimed to investigate: (1) what haptic systems (in terms of function, haptic signal, channel, and supported task) have been experimentally tested, (2) how these haptic systems have been evaluated, and (3) their reported effects on driver performance and behaviour. We reviewed empirical research in which participants had to drive a vehicle in a real or simulated environment, were able to control the heading and/or speed of the vehicle, and a haptic signal was provided to them. The results indicated that a clear distinction can be made between warning systems (using vibrations) and guidance systems (using continuous forces). Studies typically used reaction time measures for evaluating warning systems and vehicle-centred performance measures for evaluating guidance systems. In general, haptic warning systems reduced the reaction time of a driver compared to no warnings, although these systems may cause annoyance. Guidance systems generally improved the performance of drivers compared to non-aided driving, but these systems may suffer from after-effects. Longitudinal research is needed to investigate the transfer and retention of effects caused by haptic support systems. PMID- 26683255 TI - Two-Colored Dental Surveying Tool as an Alternative for Carbon Marker. AB - Various tools are used with a dental surveyor, including analyzing rods, carbon markers, undercut gauges, and protective sheaths for a specific function. A carbon marker is a parallel-sided carbon rod used to mark the survey line on a cast or a crown on a cast. The carbon marker (with or without protective sheath) cannot differentiate more than one survey line on the cast if needed. The wear of the carbon marker along the parallel walls after repeated use may give an incorrect survey line. We suggest a simple modification in the analyzing rod to prepare a two-colored surveying tool. An analyzing rod is a parallel-sided rod used to analyze the relative parallelism of two or more surfaces of a cast and to mark survey lines on wax patterns. With the modified analyzing rod, the survey lines can be marked with two colors, and the problem of breaking of the carbon marker also can be eliminated. PMID- 26683256 TI - Imaging properties of high aspect ratio absorption gratings for use in preclinical x-ray grating interferometry. AB - X-ray grating interferometry is one among various methods that allow extracting the so-called phase and visibility contrasts in addition to the well-known transmission images. Crucial to achieving a high image quality are the absorption gratings employed. Here, we present an in-depth analysis of how the grating type and lamella heights influence the final images. Benchmarking gratings of two different designs, we show that a frequently used proxy for image quality, a grating's so-called visibility, is insufficient to predict contrast-to-noise ratios (CNRs). Presenting scans from an excised rat lung, we demonstrate that the CNRs obtained for transmission and visibility images anti-correlate. This is explained by the stronger attenuation implied by gratings that are engineered to provide high visibilities by means of an increased lamella height. We show that even the visibility contrast can suffer from this effect when the associated reduced photon flux on the detector is not outweighed by a corresponding gain in visibility. Resulting in an inevitable trade-off between the quality of the two contrasts, the question of how an optimal grating should be designed can hence only be answered in terms of Pareto optimality. PMID- 26683257 TI - Epidermal Growth Factor Receptor Mutation in Small Cell Lung Cancer Patients in an Indian Tertiary Care Oncology Hospital: Incidence and Clinical Outcome. PMID- 26683258 TI - Techniques and Outcome of Surgery for Locally Advanced and Local Recurrent Rectal Cancer. AB - Locally advanced primary rectal cancer is variably defined, but generally refers to T3 and T4 tumours. Radical surgery is the mainstay of treatment for these tumours but there is a high-risk for local recurrence. National Institute for Health and Care Excellence (2011) guidelines recommend that patients with these tumours be considered for preoperative chemoradiotherapy and this is the starting point for any discussion, as it is standard care. However, there are many refinements of this pathway and these are the subject of this overview. In surgical terms, there are two broad settings: (i) patients with tumours contained within the mesorectal envelope, or in the lower rectum, limited to invading the sphincter muscles (namely some T2 and most T3 tumours); and (ii) patients with tumours directly invading or adherent to pelvic organs or structures, mainly T4 tumours - here referred to as primary rectal cancer beyond total mesorectal excision (PRC-bTME). Major surgical resection using the principles of TME is the mainstay of treatment for the former. Where anal sphincter sacrifice is indicated for low rectal cancers, variations of abdominoperineal resection - referred to as tailored excision - including the extralevator abdominoperineal excision (ELAPE), are required. There is debate whether or not plastic reconstruction or mesh repair is required after these surgical procedures. To achieve cure in PRC-bTME tumours, most patients require extended multivisceral exenterative surgery, carried out within specialist multidisciplinary centres. The surgical principles governing the treatment of recurrent rectal cancer (RRC) parallel those for PRC bTME, but typically only half of these patients are suitable for this type of major surgery. Peri-operative morbidity and mortality are considerable after surgery for PRC-bTME and RRC, but unacceptable levels of variation in clinical practice and outcome exist globally. To address this, there are now major efforts to standardise terminology and classifications, to allow appropriate comparisons in future studies. PMID- 26683260 TI - Dimensions, energetics, and denaturant effects of the protein unstructured state. AB - Determining the energetics of the unfolded state of a protein is essential for understanding the folding mechanics of ordered proteins and the structure function relation of intrinsically disordered proteins. Here, we adopt a coil globule transition theory to develop a general scheme to extract interaction and free energy information from single-molecule fluorescence resonance energy transfer spectroscopy. By combining protein stability data, we have determined the free energy difference between the native state and the maximally collapsed denatured state in a number of systems, providing insight on the specific/nonspecific interactions in protein folding. Both the transfer and binding models of the denaturant effects are demonstrated to account for the revealed linear dependence of inter-residue interactions on the denaturant concentration, and are thus compatible under the coil-globule transition theory to further determine the dimension and free energy of the conformational ensemble of the unfolded state. The scaling behaviors and the effective theta-state are also discussed. PMID- 26683259 TI - Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease. AB - OBJECTIVE AND DESIGN: To examine the effect of 3-[(dodecylthiocarbonyl)-methyl] glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells. MATERIALS AND METHODS: Colitis was induced by rectally infusing trinitrobenzenesulfonic acid (TNBS) (1.5 mg in 50% ethanol) in BALB/c mice or orally administering 3% dextran sulfate sodium (DSS) for 5 days in C57BL/6 mice. The severity of colitis was assessed after intraperitoneally injecting DTCM-G (40 mg/kg). The anti-inflammatory properties of DTCM-G and its mechanisms were investigated in LPS-stimulated RAW264.7 cells. RESULTS: DTCM-G significantly ameliorated TNBS-induced colitis, according to the body weight loss, disease activity index, colonic obstruction, macroscopic colonic inflammation score, mucosal myeloperoxidase activity, and histopathology. Immunohistochemistry and isolated lamina propria mononuclear cells showed significantly reduced colonic F4/80(+) and CD11b(+) macrophage infiltration. DTCM G significantly suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL) 6 messenger RNA expression in the colon and attenuated DSS-induced colitis, according to the disease activity index and histopathology. In RAW264.7 cells, DTCM-G suppressed LPS-induced TNF-alpha/IL-6 production and enhanced glycogen synthase kinase-3beta phosphorylation. CONCLUSIONS: DTCM-G attenuated murine experimental colitis by inhibiting macrophage infiltration and inflammatory cytokine expression. Thus, DTCM-G may be a promising treatment for inflammatory bowel disease. PMID- 26683261 TI - Exposure of Cucurbita pepo to DDE-contamination alters the endophytic community: A cultivation dependent vs a cultivation independent approach. AB - 2,2-bis(p-chlorophenyl)-1,1-dichloro-ethylene (DDE) is the most abundant and persistent degradation product of the pesticide 2,2-bis(p-chlorophenyl)-1,1,1 trichloroethane (DDT) and is encountered in contaminated soils worldwide. Both DDE and DDT are classified as Persistent Organic Pollutants (POPs) due to their high hydrophobicity and potential for bioaccumulation and biomagnification in the food chain. Zucchini (Cucurbita pepo ssp. pepo) has been shown to accumulate high concentrations of DDE and other POPs and has been proposed as a phytoremediation tool for contaminated soils. The endophytic bacteria associated with this plant may play an important role in the remedial process. Therefore, this research focuses on changes in endophytic bacterial communities caused by the exposure of C. pepo to DDE. The total bacterial community was investigated using cultivation independent 454 pyrosequencing, while the cultivable community was identified using cultivation-dependent isolation procedures. For both procedures, increasing numbers of endophytic bacteria, as well as higher diversities of genera were observed when plants were exposed to DDE. Several bacterial genera such as Stenotrophomonas sp. and Sphingomonas sp. showed higher abundance when DDE was present, while, for example Pseudomonas sp. showed a significantly lower abundance in the presence of DDE. These findings suggest tolerance of different bacterial strains to DDE, which might be incorporated in further investigations to optimize phytoremediation with the possible use of DDE-degrading endophytes. PMID- 26683262 TI - The presence of cardiophrenic angle lymph nodes is not an indicator of peritoneal carcinomatosis from colorectal cancer on MDCT: Results of a case-control study. AB - OBJECTIVE: To determine if the presence of cardiophrenic angle lymph nodes (CPALNs) on multidetector-row computed tomography (MDCT) can be considered as an indicator of peritoneal carcinomatosis (PC) in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Two groups of 101 patients each were retrospectively included. Group 1 included patients with PC from CRC and Group 2 included patients with CRC without PC. MDCT examinations were analyzed by two readers working in consensus for the presence or absence of CPALNs and, when present for their dimensions (short and long axis), location (right, left or bilateral) and shape (oval or rounded). RESULTS: Prevalence of CPALNs was 29% in Group 1 and 32% in Group 2. No differences in prevalence of CPALNs were found between the two groups (P = 0.458). Presence of CPALNs had a sensitivity of 29% (95%CI: 23-35%) for the diagnosis of PC and a specificity of 68% (95%CI = 62-74%). No differences in CPALN dimensions, location and shape were found between these two groups. CONCLUSION: Presence of CPALNs cannot be considered as an indicator of PC in patients with CRC. In addition, when present, CPALNs have similar dimensions, location and shapes in patients with PC from CRC than in those without PC. PMID- 26683263 TI - Evaluation of resectability after neoadjuvant chemotherapy for primary non resectable colorectal liver metastases: A multicenter study. AB - BACKGROUND/AIM: The Kyushu Study Group of Clinical Cancer (KSCC) previously reported the safety and efficacy of neoadjuvant chemotherapy with mFOLFOX6 + bevacizumab for H2/H3 liver metastases of colorectal cancer. The aim of the current study was to evaluate the resectability of these metastases before and after chemotherapy as determined by independent liver surgeons. METHODS: Between May 2008 and April 2010, 40 patients were registered in a multicenter phase 2 trial of neoadjuvant chemotherapy (KSCC 0802). In Study 1, 5 independent liver surgeons from five different KSCC centers evaluated the resectability of liver metastases of colorectal cancer based on imaging studies performed before and after chemotherapy. Each surgeon was blinded to the other surgeons' evaluations. In addition, no information about the patients' characteristics was provided. In Study 2, 3 surgeons evaluated the resectability of these lesions based on imaging studies with discussion with each other, with the surgeons being provided with information on the patients' characteristics. RESULTS: In Study 1, 13 patients (36.1%) were evaluated to be resectable at baseline, whereas 17 patients (47.2%) were evaluated to be resectable after chemotherapy. In Study 2, 4 patients (11.1%) were evaluated to be resectable at baseline, compared to 23 patients (63.9%) after chemotherapy. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOX6 + bevacizumab was confirmed to increase the resectability of non-resectable liver metastases of colorectal cancer according to the independent assessments of surgeons. PMID- 26683264 TI - Could soluble urokinase plasminogen receptor (suPAR) be used as a diagnostic biomarker for ventilator-associated pneumonia? AB - BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that is increasingly used for evaluation of systemic inflammation. This study was performed to investigate whether suPAR may possess a diagnostic value in patients with ventilator-associated pneumonia (VAP). METHODS: This clinical study was performed in the anesthesia intensive care units (ICUs) of our university. In addition to descriptive data, WBC, serum levels of C-reactive protein (CRP) and suPAR prior to and after development of VAP were noted and compared in 31 patients (22 men, 9 women) diagnosed with VAP (Study Group) and 19 patients without VAP (Control Group) in ICU (14 men, 5 women). RESULTS: The suPAR (P = 0.023), CRP (P = 0.037), WBCs (P = 0.024) in patients with VAP were significantly higher than patients without VAP. There was no remarkable difference in terms of WBCs (P = 0.052) and suPAR levels (P = 0.616) between groups on the first day of connection to mechanical ventilator. The suPAR and CRP levels in patients with VAP were significantly higher than prior to development of VAP (P = 0.001 for both). Area under curve value after diagnosis of pneumonia was found 0.248 (P = 0.002). CONCLUSION: To conclude, our results suggest that suPAR can be a useful diagnostic biomarker in patients with VAP. However, clinical trials on larger series are warranted to explore the clinical significance more accurately. PMID- 26683265 TI - The TyG index may predict the development of cardiovascular events. AB - BACKGROUND: Cardiovascular disease (CVD) is the worldwide leading cause of morbidity and mortality. An early risk detection of apparently healthy people before CVD onset has clinical relevance in the prevention of cardiovascular events. We evaluated the association between the product of fasting plasma glucose and triglycerides (TyG index) and CVD. MATERIAL AND METHODS: A total of 5014 patients of the Vascular Metabolic CUN cohort (VMCUN cohort) were followed up during a median period of 10 years. We used a Cox proportional-hazard ratio with repeated measures to estimate the risk of incidence of CVD across quintiles of the TyG index, calculated as ln[fasting triglycerides (mg/dL) * fasting plasma glucose (mg(dL)/2], and plotted a receiver-operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the Framingham risk score, a new model containing the Framingham variables with the TyG index, and the risk of coronary heart disease. RESULTS: A higher level of TyG index was significantly associated with an increased risk of developing CVD independent of confounding factors with a value of 2.32 (95% CI: 1.65-3.26) for those in the highest quintile and 1.52 (95% CI: 1.07-2.16) for those in the fourth quintile. The areas under the curve (AUC) of the ROC plots were 0.708 (0.68-0.73) for the Framingham model and 0.719 (0.70-0.74) for the Framingham + TyG index model (P = 0.014). CONCLUSIONS: The TyG index, a simple measure reflecting insulin resistance, might be useful to early identify individuals at a high risk of developing a cardiovascular event. PMID- 26683266 TI - Depression and anxiety symptoms following cancer diagnosis: a cross-sectional study. AB - INTRODUCTION: The aims of the present study were to assess demographic and clinical characteristics of patients after receiving a cancer diagnosis, and to determine possible risk factors for anxiety and depression. METHODS: All consecutive patients aged 18 or above, were assessed before starting intravenous chemotherapy for the first time with the Hospital Anxiety and Depression Scale (HADS), the Distress Thermometer, and a Visual Analog Scale for pain. Demographic and clinical data were also collected. RESULTS: The patients assessed (n = 270) had a mean age of 59.4 (SD = 11.8) years, and 50.7% were women. Tumours were more frequently colorectal (27.2%), lung (18.8%) and breast (17.6%), and 68.9% were stages 3 or 4. A HADS Anxiety score >=8 was present in 30% of the patients, a Depression score >=8 in 24.1%, and a Distress score >=4 in 44.4%. Independent risk factors for HADS Depression score >=8 were being a woman (OR = 2.45; p = 0.004), being older (OR = 1.04; p = 0.005), and cancer stage 3-4 (OR = 2.24; p = 0.023) in the multivariable analysis; for Anxiety >=8 they were being a woman (OR = 2.47; p = 0.002), having a past psychiatric consultation (OR = 2.83; p = 0.029), and cancer stage 3-4 (OR = 1.90; p = 0.047). CONCLUSION: These results suggest the need for greater awareness and a differentiated approach to patients at increased risk of anxiety and depression in the early stages of treatment and before starting chemotherapy. PMID- 26683267 TI - Upscaling behavioural studies to the field using acoustic telemetry. AB - Laboratory-based behavioural assays are often used in ecotoxicological studies to assess the environmental risk of aquatic contaminants. While results from such laboratory-based risk assessments may be difficult to extrapolate to natural environments, technological advancements over the past decade now make it possible to perform risk assessments through detailed studies of exposed individuals in natural settings. Acoustic telemetry is a technology to monitor movement and behaviour of aquatic organism in oceans, lakes, and rivers. The technology allows for tracking of multiple individuals simultaneously with very high temporal and spatial resolution, with the option to incorporate sensors to measure various physiological and environmental parameters. Although frequently used in fisheries research, aquatic ecotoxicology has been slow to adopt acoustic telemetry as a tool in field-based studies. This mini-review intends to introduce acoustic telemetry to aquatic ecotoxicologists, focusing on the potential of the technology to bridge the gap between laboratory assays and natural behaviours when making toxicological risk assessments. PMID- 26683279 TI - Protein lipid modifications--More than just a greasy ballast. AB - Covalent lipid modifications of proteins are crucial for regulation of cellular plasticity, since they affect the chemical and physical properties and therefore protein activity, localization, and stability. Most recently, lipid modifications on proteins are increasingly attracting important regulatory entities in diverse signaling events and diseases. In all cases, the lipid moiety of modified proteins is essential to allow water-soluble proteins to strongly interact with membranes or to induce structural changes in proteins that are critical for elemental processes such as respiration, transport, signal transduction, and motility. Until now, roughly about ten lipid modifications on different amino acid residues are described at the UniProtKB database and even well-known modifications are underrepresented. Thus, it is of fundamental importance to develop a better understanding of this emerging and so far under-investigated type of protein modification. Therefore, this review aims to give a comprehensive and detailed overview about enzymatic and nonenzymatic lipidation events, will report their role in cellular biology, discuss their relevancy for diseases, and describe so far available bioanalytical strategies to analyze this highly challenging type of modification. PMID- 26683280 TI - Mutation analysis with random DNA identifiers (MARDI) catalogs Pig-a mutations in heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats. AB - Identification of mutations induced by xenotoxins is a common task in the field of genetic toxicology. Mutations are often detected by clonally expanding potential mutant cells and genotyping each viable clone by Sanger sequencing. Such a "clone-by-clone" approach requires significant time and effort, and sometimes is even impossible to implement. Alternative techniques for efficient mutation identification would greatly benefit both basic and regulatory genetic toxicology research. Here, we report the development of Mutation Analysis with Random DNA Identifiers (MARDI), a novel high-fidelity Next Generation Sequencing (NGS) approach that circumvents clonal expansion and directly catalogs mutations in pools of mutant cells. MARDI uses oligonucleotides carrying Random DNA Identifiers (RDIs) to tag progenitor DNA molecules before PCR amplification, enabling clustering of descendant DNA molecules and eliminating NGS- and PCR induced sequencing artifacts. When applied to the Pig-a cDNA analysis of heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats, MARDI detected nearly all Pig-a mutations that were previously identified by conventional clone-by-clone analysis and discovered many additional ones consistent with DMBA exposure: mostly A to T transversions, with the mutated A located on the non-transcribed DNA strand. PMID- 26683281 TI - Verifying Validity of the Household Dietary Diversity Score: An Application of Rasch Modeling. AB - BACKGROUND: The Household Dietary Diversity Score (HDDS) was developed to measure household food access, one of the levels of food security. Previous research has shown dietary diversity is related to food security. However, the validity of the HDDS in the form developed by the Food and Nutrition Technical Assistance (FANTA) project-12 food groups, 24-hour recall-and most frequently used by development organizations and nongovernmental organizations has never been verified. OBJECTIVE: To verify the construct validity of the HDDS. METHODS: A Rasch model was used to test the extent to which the HDDS meets the criteria required for interval scale measurement, using data from 1015 households in Colombia and Ecuador. RESULTS: Different dietary patterns between Colombia and Ecuador and 2 cultural groups within Ecuador required data to be split into 3 subgroups. For each subgroup, the food groups meeting the criteria and their difficulty ranking were different. Refined indices, containing only those food groups meeting the criteria, contained 7 items in Colombia, 10 for Kichwa households in Ecuador, and 9 for migrant households. CONCLUSION: The indicator in its current form does not meet all criteria. Even when analyzing culturally homogenous subgroups within a small region, the components of the indicator do not form a reliable way of measuring household-level food access. PMID- 26683282 TI - (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. AB - OBJECTIVES: To examine the detection rates of (68) Ga-PSMA-positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management. MATERIALS AND METHODS: A total of 300 consecutive patients with prostate cancer (PCa) who underwent (68) Ga-PSMA-PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan-I) database. For the present analysis, we included patients with BCR (prostate-specific antigen [PSA] level >=0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito-Urinary Group (FROGG) guidelines. Two readers assessed each (68) Ga-PSMA PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological (68) Ga-PSMA uptake was investigated, and detection rates were determined according to PSA level. RESULTS: A total of 70 patients were included, and 53 positive (68) Ga-PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05-0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1-0.19 ng/mL, 23%; PSA 0.2-0.29 ng/mL, 58%; PSA 0.3-0.49 ng/mL, 36%; and PSA 0.5-0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological (68) Ga PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the (68) Ga-PSMA findings there was a major management change in 20 (28.6%) patients. CONCLUSIONS: (68) Ga-PSMA appears to be useful for re-staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to (68) Ga-PSMA findings. PMID- 26683283 TI - The intermediate host immune response in cystic echinococcosis. AB - Cystic echinococcosis (CE) is a chronic, complex and neglected zoonotic infection. In most cases, CE cysts and the intermediate host co-habit for a long time in the absence of symptoms and elicit very little inflammation. However, the immune interplay between the parasite and the host is complex, encompassing effective parasite-killing immune mechanisms implemented by the host, which in turn are modulated by the parasite. The immune response to the parasite has been exploited for the diagnosis of the disease and for the development of an effective vaccine to use in the natural intermediate host, but the mechanisms of parasite killing and immunomodulation are still unknown. Here, we reviewed the immune effector mechanisms and the strategies of immune evasion in the intermediate host. PMID- 26683284 TI - Future primary care in Norway: valid goals without clear strategies. PMID- 26683285 TI - Risk factors for excessive benzodiazepine use in a working age population: a nationwide 5-year survey in Norway. AB - OBJECTIVE: To identify risk factors for becoming an excessive user over time. SETTING: Prescription database study over five years. SUBJECTS AND METHOD: Norwegians between 30 and 60 years with a first dispensation of a benzodiazepine during 2006, encompassing 23 227 individuals. A Cox hazard regression model was defined, initially stratifying on gender, age, county, previous relevant drug dispensations, household income, education level, and vocational rehabilitation support. MAIN OUTCOME MEASURE: The time from the first redemption until excessive use was defined as using more than two DDDs per day on average within a three month period. RESULTS: Women's risk was lower than men's for excessive use (HR = 0.42, CI 0.35-0.51). Initial oxazepam, alprazolam, or nitrazepam/flunitrazepam use indicated higher risk compared with diazepam (HR = 1.51, CI 1.24-1.85, HR = 2.75, CI 1.54-4.91, HR = 1.67, CI 1.29-2.16). Previous antidepressants or lithium, antipsychotics or opioids, anti-alcohol and smoke cessation treatment indicated a higher risk compared with no such use (HR = 1.4, CI 1.16-1.69, HR = 1.92, CI 1.54-2.4, and HR = 2.88, CI 2-4.15). Higher education and average or high household income were associated with a low risk compared with low education and income (HR = 0.68, CI 0.57-0.81, HR = 0.58, CI 0.46-0.73, and HR = 0.37, CI 0.26-0.54). Working in the private or public sector was associated with a low risk compared with no registered work (HR = 0.53, CI 0.4-0.71 and HR = 0.57, CI 0.45-0.74). CONCLUSION: The prevalence of excessive use over a five-year observation period was 2.34%. Risk factors were indications of psychiatric illness, first benzodiazepine choice, low income, and education. Excessive users were also characterized by a more severe disease, indicated by having prescription fulfilments by a psychiatrist and by switching benzodiazepines. Key points Guidelines state that benzodiazepines should be used for a short time and excessive use indicates drug dependency. Of all new benzodiazepine users 2.34% became excessive users, defined as consuming above two defined daily doses (DDDs) per day on average over three months, within a five-year period. Previous use of other psychotropic drugs, opioids and anti-alcohol and smoke cessation drugs, first benzodiazepine prescribed, low household income, and low education were risk factors for excessive use. Excessive users were characterized by switching benzodiazepines and having prescription fulfilments by a psychiatrist suggesting a more severe disease. PMID- 26683286 TI - Drug prescription rates in secondary cardiovascular prevention in old age: Do vulnerability and severity of the history of cardiovascular disease matter? AB - OBJECTIVE: To assess the influence vulnerability and severity of cardiovascular disease (CVD), on prescription rates of secondary cardiovascular preventive drugs in old age. DESIGN: Population-based observational study within the ISCOPE study. SETTING: General practices in the Netherlands. SUBJECTS: A total of 1350 patients with a history of CVD (median age 81 years, 50% female). MAIN OUTCOME MEASURES: One-year prescription rates of lipid-lowering drugs and antithrombotics were obtained from the electronic medical records of 46 general practitioners (GPs). Prescription of both drugs for >= 270 days per year was considered optimal. GPs made a judgement of vulnerability. Severity of CVD was expressed as major (myocardial infarction, stroke, or arterial surgery) versus minor (angina, transient ischaemic attack, or claudication). RESULTS: GPs considered 411 (30%) participants to be vulnerable and 619 (55%) participants had major CVD. Optimal treatment was prescribed to 680 (50%) participants, whereas 370 (27%) received an antithrombotic drug only, 53 (4%) a lipid-lowering drug only, and 247 (18%) received neither. Optimal treatment was lower in participants aged >= 85 years (OR 0.37 [95% CI 0.29-0.48]), in females (OR 0.63 [0.50-0.78]), in vulnerable persons (OR 0.79 [0.62-0.99]) and in participants with minor CVD (OR 0.65 [0.53 0.81]). Multivariate ORs remained similar whereas vulnerability lost its significance (OR 0.88 [0.69-1.1]). CONCLUSION: In old age, GPs' judgement of vulnerability is not independently associated with lower treatment rates of both lipid-lowering drugs and antithrombotics, whereas a history of minor CVD is. Individual proactive re-evaluation of preventive treatment in older (female) patients, especially those with a history of minor CVD, is recommended. Key points Prescriptions of lipid-lowering drugs and antithrombotics in secondary cardiovascular prevention tend to decline with age. In this study with median age 81 years, 50% of participants received optimal treatment with both lipid-lowering drugs and antithrombotics. GPs' judgement of vulnerability was not independently associated with optimal treatment. A history of less severe cardiovascular disease was independently associated with lower prescription rates of lipid lowering drugs and antithrombotics. Proactive individual re-evaluation of cardiovascular preventive treatment in older (female) patients, especially patients with less severe cardiovascular disease, is recommended. PMID- 26683287 TI - Appropriateness of antibiotic prescribing for upper respiratory tract infections in general practice: Comparison between Denmark and Iceland. AB - OBJECTIVE: To compare the appropriateness of antibiotic prescribing for upper respiratory tract infections (URTIs) in two countries with different prevalence of antimicrobial resistance: Denmark and Iceland. DESIGN: A cross-sectional study. SETTINGS AND SUBJECTS: General practitioners (GPs) in Denmark (n = 78) and Iceland (n = 21) registered all patients with URTI according to the Audit Project Odense (APO) method during a three-week period in the winter months of 2008 and 2009. MAIN OUTCOME MEASURES: Appropriateness of antibiotic prescribing in patients with URTI in Denmark and Iceland. RESULTS: A total of 1428 patients were registered (Denmark: n = 1208; Iceland: n = 220). A majority of patients in both countries were prescribed antibiotics, and only a minority of the prescriptions could be classified as appropriate prescribing. In general, Icelandic GPs more often prescribed antibiotics (Iceland = 75.8% vs. Denmark = 59.3%), but Danish GPs had a higher percentage of inappropriate antibiotic prescribing for sinusitis, and Icelandic GPs for pharyngotonsillitis. No differences were found for acute otitis media (AOM). The different antibiotic prescribing patterns between Denmark and Iceland could not fully be explained by different symptoms and signs among patients. CONCLUSION: Icelandic GPs have a higher antibiotic prescribing rate compared with Danish GPs, but the percentage of inappropriate antibiotic prescribing is highest in Denmark for sinusitis, and in Iceland for pharyngotonsillitis. Key points Within the Nordic countries there are marked differences in antimicrobial resistance and antibiotic use. Iceland differs from Denmark by a higher antibiotic prescribing rate and a higher prevalence of antimicrobial resistance. The majority of antibiotics are prescribed in primary care and most often for upper respiratory infections (URTIs). Only a minor amount of antibiotic prescriptions for URTIs can be classified as appropriate; inappropriate antibiotic prescribing is higher in Denmark than in Iceland for sinusitis and the opposite for pharyngotonsillitis. The different antibiotic prescribing patterns between Denmark and Iceland cannot be fully explained by different clinical criteria among patients. PMID- 26683288 TI - Primary-care-based episodes of care and their costs in a three-month follow-up in Finland. AB - OBJECTIVE: To explore patient characteristics, resource use, and costs related to different episodes of care (EOC) in Finnish health care. DESIGN: Data were collected during a three-month prospective, non-randomized follow-up study (Effective Health Centre) using questionnaires and an electronic health record. SETTING: Three primary health care practices in Pirkanmaa, Finland. SUBJECTS: Altogether 622 patients were recruited during a one-week period. Inclusion criteria: the patient had a doctor's or nurse's appointment on the recruiting day and agreed to participate. Exclusion criteria: patients visiting a specialized health guidance clinic for pregnant women, children, and mothers. MAIN OUTCOME MEASURES: Patient characteristics, resource use, and costs based on the ICPC-2 EOC classification. RESULTS: On average, the patients had 1.22 EOCs during the three months. Patient characteristics and resource use differed between the EOC chapters. Chapter L, "Musculoskeletal", had the most episodes (17%). The most common (8%) single EOC was "upper respiratory infection". The mean cost of an episode (COE) was ?389.56 (standard error 61.11) and the median COE was ?165.00 (interquartile range ?118.46-288.56) during the three-month follow-up. The most expensive chapter was K, "Circulatory", with a mean COE of ?909.85. The most expensive single COE was in chapter K, ?32 545.56. The most expensive 1% of the COEs summed up covered 36% of the total COEs. CONCLUSION: Patient characteristics, resource use, and costs differed between the ICPC-2 chapters, which could be taken into account in service planning and pricing. Future studies should incorporate more specific diagnoses, larger data sets, and longer follow up times. Key points The most common episodes were under the ICPC-2 "Musculoskeletal" chapter, but the highest mean and single-episode costs were related to the "Circulatory" chapter. The mean (median) cost of episodes that started in primary care was ?390 (?165) during the three-month follow-up. Patient characteristics, resource use, and costs differed significantly between the ICPC 2 chapters. The most expensive 1% of the episodes covered 36% of the total costs of all the episodes. PMID- 26683289 TI - Postpartum mental health study flawed by fetal loss omission. PMID- 26683301 TI - US device industry and FDA "colluded" on legislation to weaken regulatory oversight. PMID- 26683303 TI - One aneurysm may hide another .... PMID- 26683302 TI - Effect of Urate-Lowering Therapy on All-Cause and Cardiovascular Mortality in Hyperuricemic Patients without Gout: A Case-Matched Cohort Study. AB - OBJECTIVES: An increased risk of mortality in patients with hyperuricemia has been reported. We examined (1) the risk of all-cause and cardiovascular disease (CVD) mortality in untreated hyperuricemic patients who did not receive urate lowering therapy (ULT), and (2) the impact of ULT on mortality risk in patients with hyperuricemia. METHODS: In this retrospective case-matched cohort study during a mean follow-up of 6.4 years, 40,118 Taiwanese individuals aged >=17 years who had never used ULT and who had never had gout were examined. The mortality rate was compared between 3,088 hyperuricemic patients who did not receive ULT and reference subjects (no hyperuricemia, no gout, no ULT) matched for age and sex (1:3 hyperuricemic patients/reference subjects), and between 1,024 hyperuricemic patients who received ULT and 1,024 hyperuricemic patients who did not receive ULT (matched 1:1 based on their propensity score and the index date of ULT prescription). Cox proportional hazard modeling was used to estimate the respective risk of all-cause and CVD (ICD-9 code 390-459) mortality. RESULTS: After adjustment, hyperuricemic patients who did not receive ULT had increased risks of all-cause (hazard ratio, 1.24; 95% confidence interval, 0.97 1.59) and CVD (2.13; 1.34-3.39) mortality relative to the matched reference subjects. Hyperuricemic patients treated with ULT had a lower risk of all-cause death (0.60; 0.41-0.88) relative to hyperuricemic patients who did not receive ULT. CONCLUSION: Under-treatment of hyperuricemia has serious negative consequences. Hyperuricemic patients who received ULT had potentially better survival than patients who did not. PMID- 26683304 TI - Posterior reversible encephalopathy syndrome with thalamic involvement during vasopressor treatment of vertebrobasilar vasospasm after subarachnoid hemorrhage. AB - Hemodynamic augmentation is the primary medical intervention employed to reverse neurological deficits associated with vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. Failure to improve despite induced hypertension (IH) may raise concern for persistent hypoperfusion and prompt even more aggressive blood pressure augmentation. However, posterior reversible encephalopathy syndrome (PRES) is a hyperperfusion syndrome reported as a rare complication of IH that may confound this picture. We report a case of PRES with prominent thalamic involvement and impaired level of consciousness secondary to blood pressure augmentation for the treatment of symptomatic vertebrobasilar vasospasm. Recognition of this syndrome in distinction to worsening ischemia is particularly critical, as normalization of blood pressure should lead to rapid clinical improvement. PMID- 26683305 TI - Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans. AB - Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's <= 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0*10-5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans. PMID- 26683306 TI - A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology. AB - Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks. PMID- 26683307 TI - A highly efficient and sensitive LC-MS/MS method for the determination of afatinib in human plasma: application to a metabolic stability study. AB - Afatinib (AFT) is a new tyrosine kinase inhibitor approved for the treatment of nonsmall cell lung cancer. In the present study, a simple, specific, rapid and sensitive liquid chromatography tandem mass-spectrometric method for the quantification of AFT in human plasma, was developed and validated. Chromatographic separation of the analytes was accomplished on a reversed-phase Luna((r)) -PFP 100 A column (50 * 2.0 mm; 3.0 MUm) maintained at ambient temperature. Isocratic elution was carried out using acetonitrile-water (40:60, v/v) containing 10 mm ammonium formate buffer (pH 4.5) adjusted with formic acid at a flow rate of 0.4 mL min(-1) . The analytes were monitored by electrospray ionization in positive ion multiple reaction monitoring mode. The method yields a linear calibration plot (r(2) = 0.9997) from a quantification range of 0.5-500 ng mL(-1) with the lower limit of quantification and lower limit of detection of 1.29 and 0.42 ng mL(-1) , respectively. The intra- and inter-day precision and accuracy were estimated and found to be in the ranges of 1.53-4.11% for precision and -2.80-0.38% for accuracy. Finally, quantification of afatinib in a metabolic stability study in rat liver microsomes was achieved through the proposed method. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26683308 TI - Evaluation of trace metal and polychlorinated biphenyl levels in tea brands of different origin commercialized in Italy. AB - The objectives of this study were to investigate the trace element (Hg, Cd, Pb, Cu, Zn, Ni, Fe, Cr and Se) and polychlorinated biphenyl (PCBs) content of several commercially available brands of green and black tea marketed in Italy. The concentrations these chemicals were found to be variable and largely dependent upon the type and brand of analysed tea. The most abundant element among the essential elements was Fe, followed by Zn, Cu, Se, Ni and Cr, whereas Pb was the predominant among the tested nonessential elements followed by Hg and Cd. Assessment based on several available guidelines showed that element content were low, except for Hg and Ni. The PCBs concentrations were generally low, with a homologue profile dominated by low-chlorinated congeners, namely three- and tetra PCBs accounting for more than 60% of the total residue. Apart from trace elements, this is the first study documenting in detail the concentrations and congener distribution of PCBs in tea samples of different origin. PMID- 26683309 TI - Toxicity and oxidative stress induced by T-2 toxin and HT-2 toxin in broilers and broiler hepatocytes. AB - T-2 and HT-2 toxins belong to mycotoxins which are found in human foods and animal chow. We investigated the toxicity and oxidative stress induced by T-2/HT 2 in broilers and chicken hepatocytes. Maize cultures of Fusarium poae was fed to broilers for 42 d, and the physiological index, biochemical index and expression of mRNAs related to oxidative stress were analyzed. Chicken hepatocytes were treated with different levels of T-2/HT-2, and the following parameters were detected: cell viability, GSH and MDA concentration, LDH leakage, activities of ALT/AST, ROS, GSH-PX, SOD and CAT, and expression of mRNA related to oxidative stress. In vivo, high levels of mycotoxins (4 mg/kg T-2 and 0.667 mg/kg HT-2) in feed caused significant reductions in body weight, weight gain, and serum total protein, and significant increases in feed conversion ratio, ALP, ALT/AST activities, and expression of mRNA related to oxidative stress. In vitro, cells treated with T-2/HT-2 showed reductions of GSH concentration and significant increases in LDH leakage, ALT/AST ROS, GSH-PX, SOD and CAT activities, MDA concentration, and expression of mRNA related to oxidative stress. Consequently, F. poae culture material and T-2/HT-2 induced toxicity and oxidative stress in vivo and in vitro, respectively. PMID- 26683310 TI - The impact of multi-walled carbon nanotubes with different amount of metallic impurities on immunometabolic parameters in healthy volunteers. AB - The impact of two types of multi-walled carbon nanotubes (MWCNTs) (12-14 nm) with different content of metallic impurities (purified and unpurified nanotubes) on peroxidation processes, the status of immune cells in healthy volunteers and gene expression combined to pathway analysis was studied in vitro. From the study it was shown that the main mechanism of action for both types of MWCNTs is induction of oxidative stress, the intensity of which is directly related to the amount of metallic impurities. Unpurified MWCNTs produced twice as high levels of oxidation than the purified CNTs inducing thus more intense mitochondrial dysfunction. All the above were also verified by gene expression analysis of 2 different human cellular cultures (lung epithelium and keratinoma cells) and the respective pathway analysis; modulation of genes activating the NFkB pathway is associated to inflammatory responses. This may cause a perturbation in the IL-6 signaling pathway in order to regulate inflammatory processes and compensate for apoptotic changes. A plausible hypothesis for the immunological effects observed in vivo, are considered as the result of the synergistic effect of systemic (mediated by cells of the routes of exposure) and local inflammation (blood cells). PMID- 26683311 TI - Different concentrations of kaempferol distinctly modulate murine embryonic stem cell function. AB - Kaempferol (3,4',5,7-tetrahydroxyflavone) is a natural flavonoid with several beneficial and protective effects. It has been demonstrated that kaempferol has anticancer properties, particularly due to its effects on proliferation, apoptosis and the cell cycle. However, possible effects on pluripotent embryonic stem cell function have not yet been addressed. Embryonic stem cells have the ability to self-renew and to differentiate into all three germ layers with potential applications in regenerative medicine and in vitro toxicology. We show that exposure of murine embryonic stem cells (mESC) to high concentrations of kaempferol (200 MUM) leads to decreased cell numbers, although the resulting smaller cell colonies remain pluripotent. However, lower concentrations of this compound (20 MUM) increase the expression of pluripotency markers in mESCs. Mitochondrial membrane potential and mitochondrial mass are not affected, but a dose-dependent increase in apoptosis takes place. Moreover, mESC differentiation is impaired by kaempferol, which was not related to apoptosis induction. Our results show that low concentrations of kaempferol can be beneficial for pluripotency, but inhibit proper differentiation of mESCs. Additionally, high concentrations induce apoptosis and increase mitochondrial reactive oxygen species (ROS). PMID- 26683312 TI - Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells. AB - Alternariol (AOH), a mycotoxin produced by Alternaria sp, appears as food contaminant in fruit, vegetables and cereal products. Its toxicity has been demonstrated, but the mechanisms involved have not been elucidated yet. In this study, the pathways triggered by AOH and degradation products generated on Caco-2 cells were evaluated. Cells were exposed to AOH sub-cytotoxic concentrations of 15, 30 and 60 MUM. Cell cycle disruption, the induction of apoptosis/necrosis and changes in mitochondrial membrane potential (Deltapsim) after 24 and 48 h was asses by flow cytometry. Also, AOH and its degradation products were evaluated after 24 and 48 h by high-performance liquid chromatography with tandem mass spectrometric (LC-MS/MS) to detect and quantify its levels. Cell cycle was significantly decreased at G1 phase and increased at S and G2/M phase at the time of exposure. AOH induced necrosis, apoptosis/necrosis and loss of Deltapsim in a dose and time-dependent manner. The concentrations of AOH quantified in the culture media exposed to AOH decreased as the exposure time was increased. In conclusion, AOH caused cytotoxic effects supported by blocking cell cycle, decreasing cell proliferation and increasing apoptosis/necrosis cells. PMID- 26683313 TI - Expression of Lactate Dehydrogenase in Aspergillus niger for L-Lactic Acid Production. AB - Different engineered organisms have been used to produce L-lactate. Poor yields of lactate at low pH and expensive downstream processing remain as bottlenecks. Aspergillus niger is a prolific citrate producer and a remarkably acid tolerant fungus. Neither a functional lactate dehydrogenase (LDH) from nor lactate production by A. niger is reported. Its genome was also investigated for the presence of a functional ldh. The endogenous A. niger citrate synthase promoter relevant to A. niger acidogenic metabolism was employed to drive constitutive expression of mouse lactate dehydrogenase (mldhA). An appraisal of different branches of the A. niger pyruvate node guided the choice of mldhA for heterologous expression. A high copy number transformant C12 strain, displaying highest LDH specific activity, was analyzed under different growth conditions. The C12 strain produced 7.7 g/l of extracellular L-lactate from 60 g/l of glucose, in non-neutralizing minimal media. Significantly, lactate and citrate accumulated under two different growth conditions. Already an established acidogenic platform, A. niger now promises to be a valuable host for lactate production. PMID- 26683314 TI - Improved cytotoxicity of pyridyl-substituted thiosemicarbazones against MCF-7 when used as metal ionophores. AB - Zinc is the second most abundant transition metal in the human body, between 3 and 10% of human genes encoding for zinc binding proteins. We have investigated the interplay of reactive oxygen species and zinc homeostasis on the cytotoxicity of the thiosemicarbazone chelators against the MCF-7 cell line. The cytotoxicity of thiosemicarbazone chelators against MCF-7 can be improved through supplementation of ionic zinc provided the zinc ion is at a level exceeding the thiosemicarbazone concentration. Elimination of the entire cell population can be accomplished with this regime, unlike the plateau of cytotoxicity observed on thiosemicarbazone monotherapy. The cytotoxic effects of copper complexes of the thiosemicarbazone are not enhanced by zinc supplementation, displacement of copper from the complex being disfavoured. Treatment of MCF-7 with uncomplexed thiosemicarbazone initiates post G1 blockade alongside the induction of apoptosis, cell death being abrogated through subsequent supplementation with zinc ion after drug removal. This would implicate a metal depletion mechanism in the cytotoxic effect of the un-coordinated thiosemicarbazone. The metal complexes of the species, however, fail to initiate similar G1 blockade and apparently exert their cytotoxic effect through generation of reactive oxygen species, suggesting that multiple mechanisms of cytotoxicity can be associated with the thiosemicarbazones dependant on the level of metal ion association. PMID- 26683315 TI - A heterotrimer model of the complete Microprocessor complex revealed by single molecule subunit counting. AB - During microRNA (miRNA) biogenesis, the Microprocessor complex (MC), composed minimally of Drosha, an RNaseIII enzyme, and DGCR8, a double-stranded RNA-binding protein, cleaves the primary-miRNA (pri-miRNA) to release the pre-miRNA stem-loop structure. Size-exclusion chromatography of the MC, isolated from mammalian cells, suggested multiple copies of one or both proteins in the complex. However, the exact stoichiometry was unknown. Initial experiments suggested that DGCR8 bound pri-miRNA substrates specifically, and given that Drosha could not be bound or cross-linked to RNA, a sequential model for binding was established in which DGCR8 bound first and recruited Drosha. Therefore, many laboratories have studied DGCR8 binding to RNA in the absence of Drosha and have shown that deletion constructs of DGCR8 can multimerize in the presence of RNA. More recently, it was demonstrated that Drosha can bind pri-miRNA substrates in the absence of DGCR8, casting doubt on the sequential model of binding. In the same study, using a single-molecule photobleaching assay, fluorescent protein-tagged deletion constructs of DGCR8 and Drosha assembled into a heterotrimeric complex on RNA, comprising two DGCR8 molecules and one Drosha molecule. To determine the stoichiometry of Drosha and DGCR8 within the MC in the absence of added RNA, we also used a single-molecule photobleaching assay and confirmed the heterotrimeric model of the human MC. We demonstrate that a heterotrimeric complex is likely preformed in the absence of RNA and exists even when full-length proteins are expressed and purified from human cells, and when hAGT-derived tags are used rather than fluorescent proteins. PMID- 26683316 TI - Editorial Commentary: Whole-Genome Sequencing of Clostridium difficile: Exquisitely Sensitive but Not Yet Optimally Applied. PMID- 26683317 TI - Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence. AB - BACKGROUND: Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain). METHODS: We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards. RESULTS: Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor-recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management. CONCLUSIONS: Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management. PMID- 26683318 TI - Exploring the association between feeding habits, non-nutritive sucking habits, and malocclusions in the deciduous dentition. AB - BACKGROUND: This study aimed to explore the association between feeding habits, non-nutritive sucking habits, and malocclusions in deciduous dentition. METHODS: A cross-sectional observational survey was carried out in 275 children aged 3 to 6 years and included clinical evaluations of malocclusions and structured interviews. Statistical significance for the association between feeding habits and the development of malocclusion was determined using chi-square and Fisher's exact tests. In addition, odds ratio (OR) calculations were used for intergroup comparisons. Controlling for confounders was adjusted by excluding children with non-nutritive sucking habits. RESULTS: The results indicated that there were no significant relationships between exclusive breastfeeding or bottlefeeding and the presence of any type of malocclusion (p > 0.05). There was also no significant association between breastfeeding or bottlefeeding duration and malocclusion (p > 0.05). In addition, it was observed that exclusive breastfeeding had a protective effect and diminished the risk of acquiring non nutritive sucking habits (p = 0.001). CONCLUSIONS: There was no association between feeding habits and malocclusions in the deciduous dentition in this sample of children. Exclusive breastfeeding reduced the risk of acquiring non nutritive sucking habits. PMID- 26683319 TI - Contribution of PBP3 Substitutions and TEM-1, TEM-15, and ROB-1 Beta-Lactamases to Cefotaxime Resistance in Haemophilus influenzae and Haemophilus parainfluenzae. AB - AIMS: To investigate the relative contributions of naturally occurring penicillin binding protein 3 (PBP3) substitutions, and TEM-1, TEM-15, and ROB-1 beta lactamases on resistance to a third-generation cephalosporin in Haemophilus influenzae and Haemophilus parainfluenzae. RESULTS: The minimum inhibitory concentration (MIC) of cefotaxime (CTX) was assessed after transformation with PCR-amplified ftsI genes expressing altered PBP3 and/or small plasmids encoding beta-lactamases into an isogenic environment of H. influenzae and H. parainfluenzae. Group III PBP3, comprising substitutions N526K, S385T, and L389F, conferred CTX resistance to H. influenzae according to EUCAST interpretative criteria. Group III-like PBP3, comprising substitutions N526H and S385T, increased the CTX MIC of H. parainfluenzae ninefold, but the level did not transgress the resistance breakpoint. Production of TEM-15 beta-lactamase conferred CTX resistance on both H. influenzae and H. parainfluenzae. A nitrocefin hydrolysis assay showed TEM-15 to be a less efficient enzyme compared to TEM-1. CONCLUSIONS: TEM-15 and PBP3 substitutions impose an additive effect on resistance to third-generation cephalosporins in both H. influenzae and H. parainfluenzae. The effect of PBP3 substitutions on beta-lactam resistance in H. parainfluenzae can be addressed by transfer of ftsI genes in vitro. PMID- 26683320 TI - Genetic and epigenetic mechanisms of NASH. AB - Along with the obesity epidemic, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased exponentially. The histological disease spectrum of NAFLD ranges from bland fatty liver (hepatic steatosis), to the concomitant presence of inflammation and ballooning which defines nonalcoholic steatohepatitis (NASH). The latter can progress in a subset to fibrosis, leading ultimately to cirrhosis and hepatocellular carcinoma. The past decade has seen tremendous advances in our understanding of the genetic and epigenetic bases of NAFLD, mainly through the application of high end technology platforms including genome-wide association studies (GWAS). These have helped to define common gene variants (minor allele frequency >5 %) that contribute to the NAFLD phenotype. Looking to the future, these discoveries are expected to lead to improved diagnostics, the personalization of medicine, and a better understanding of the pathophysiological underpinnings that drive the transition from NAFLD to steatohepatitis and fibrosis, leading to the identification of novel therapeutic targets. In this review, we summarize data on the current state of knowledge with regard to the genetic and epigenetic mechanisms for the development of NASH. PMID- 26683322 TI - MERS-CoV geography and ecology in the Middle East: analyses of reported camel exposures and a preliminary risk map. AB - BACKGROUND: Middle Eastern respiratory syndrome coronavirus (MERS-CoV) has spread rapidly across much of the Middle East, but no quantitative mapping of transmission risk has been developed to date. Moreover, details of the transmission cycle of the virus remain unclear, particularly regarding the role of camels as a reservoir host for human infections. METHODS: We present a first analysis of the environmental circumstances under which MERS-CoV cases have occurred in the Middle East, covering all case occurrences through May 2015, using ecological niche modeling approaches to map transmission risk. We compare the environmental breadth of conditions under which cases have reported camel contacts with that of the broader population of all cases, to assess whether camel-associated cases occur under a more restricted set of environmental circumstances. RESULTS: We documented geographic and environmental distributions of MERS-CoV cases across the Middle East, and offer preliminary mapping of transmission risk. We confirm the idea that climatic dimensions of camel associated cases are more constrained and less variable than the broader suite of case occurrences; hence, camel exposure may be a key limiting element in MERS-CoV transmission. CONCLUSION: This study offers a first detailed geographic and environmental analysis of MERS-CoV distributions across the Middle East. Results indicated that camel-exposed cases occur under a narrower suite of environmental conditions than non-camel-exposed cases, suggesting perhaps a key role for camels in the transmission of the disease, and perhaps a narrower area of risk for 'primary,' camel-derived cases of MERS. PMID- 26683321 TI - Serum and synovial cartilage oligomeric matrix protein levels in early and established rheumatoid arthritis. AB - OBJECTIVE: To assess cartilage oligomeric matrix protein (COMP) levels in serum and synovial fluid in patients with early and established rheumatoid arthritis (RA), and to correlate the levels with clinical, laboratory and radiological characteristics. PATIENTS AND METHODS: The study included 24 female RA patients. Full medical history was taken, thorough clinical examination and laboratory investigations performed, and body mass index (BMI) recorded. Radiological damage was assessed according to the modified Larsen score. Disease activity score 28 (DAS28) was calculated. The control group comprised 30 age- and gender-matched healthy subjects. Serum and synovial COMP levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean patient age was 44.04 +/- 10.5 years. Of the 24 patients, 12 had early RA and 12 had established disease with joint destruction; 5 of each group had knee effusion. Serum COMP was significantly higher in patients (19.54 +/- 5.47 ug/ml) compared to controls (5.93 +/- 1.95 ug/ml; p < 0.001) and was also significantly higher in patients with established disease (23.9 +/- 3.1 ug/ml) compared to those in early stages (15.1 +/- 3.2 ug/ml; p < 0.001). Synovial COMP was also significantly increased in established compared to early-stage RA (31.2 +/- 9.8 ug/ml vs. 51.6 +/- 10.4 ug/ml; p = 0.013). Serum and synovial COMP significantly correlated with age, disease duration, BMI, DAS28 and modified Larsen score. On performing regression analysis in RA patients, only BMI could predict the serum level of COMP (p = 0.02). CONCLUSION: COMP is a promising biomarker for disease activity in RA, making it a potential therapeutic target. The obvious correlation with the BMI throws light on the importance of weight control not only in osteoarthritis (OA), but also in RA. PMID- 26683323 TI - Loss of intraepidermal nerve fiber density during SIV peripheral neuropathy is mediated by monocyte activation and elevated monocyte chemotactic proteins. AB - BACKGROUND: Peripheral neuropathy (PN) continues to be a major complication of human immunodeficiency virus (HIV) infection despite successful anti-retroviral therapy. Human HIV-PN can be recapitulated in a CD8-depleted, simian immunodeficiency virus (SIV)-infected rhesus macaque animal model, characterized by a loss of intraepidermal nerve fiber density (IENFD) and damage to the dorsal root ganglia (DRG). Increased monocyte traffic to the DRG has previously been associated with severe DRG pathology, as well as a loss in IENFD. Here, we sought to characterize the molecular signals associated with monocyte activation and trafficking to the DRGs. METHODS: Eleven SIV-infected CD8-depleted rhesus macaques were compared to four uninfected control animals. sCD14, sCD163, sCD137, regulated on activation normal T cell expressed and secreted (RANTES), and monocyte chemoattractant protein 1 (MCP-1) were measured in plasma and the latter three proteins were also quantified in DRG tissue lysates. All SIV-infected animals received serial skin biopsies to measure IENFD loss as well as BrdU inoculations to measure monocyte turnover during the course of infection. The number of BrdU+ and CD14+ CD16+ peripheral blood monocytes was determined by flow cytometry. The number of MAC387+, CCR2+, CCR5+, and CD137+ cells in DRG tissue was quantified by immunohistochemistry. RESULTS: sCD14, sCD163, MCP-1, and sCD137 increased significantly in plasma from pre-infection to necropsy. Plasma sCD163 and RANTES inversely correlated with IENFD. Additionally, sCD137 in DRG tissue lysate was elevated with severe DRG pathology and associated with the recruitment of MAC387+ cells to DRG. Elevated numbers of CCR5+ and CCR2+ satellite cells in the DRG were found, suggesting a chemotactic role of their ligands, RANTES, and MCP-1 in recruiting monocytes to the tissue. CONCLUSIONS: We characterized the role of systemic (plasma) and tissue-specific (DRG) monocyte activation and associated cytokines in the pathogenesis of SIV-PN. We identified sCD163 and RANTES as potential biomarkers for HIV-PN, as these were associated with a loss of IENFD. Additionally, we identified CD137 signaling to play a role in MAC387+ cell traffic to DRG and possibly contribute to severe pathology. These studies highlight the role of monocyte activation and traffic in the pathogenesis of SIV PN, while identifying specific signaling proteins for future pharmacological blockade. PMID- 26683335 TI - Age Effects in L2 Grammar Processing as Revealed by ERPs and How (Not) to Study Them. AB - In this study we investigate the effect of age of acquisition (AoA) on grammatical processing in second language learners as measured by event-related brain potentials (ERPs). We compare a traditional analysis involving the calculation of averages across a certain time window of the ERP waveform, analyzed with categorical groups (early vs. late), with a generalized additive modeling analysis, which allows us to take into account the full range of variability in both AoA and time. Sixty-six Slavic advanced learners of German listened to German sentences with correct and incorrect use of non-finite verbs and grammatical gender agreement. We show that the ERP signal depends on the AoA of the learner, as well as on the regularity of the structure under investigation. For gender agreement, a gradual change in processing strategies can be shown that varies by AoA, with younger learners showing a P600 and older learners showing a posterior negativity. For verb agreement, all learners show a P600 effect, irrespective of AoA. Based on their behavioral responses in an offline grammaticality judgment task, we argue that the late learners resort to computationally less efficient processing strategies when confronted with (lexically determined) syntactic constructions different from the L1. In addition, this study highlights the insights the explicit focus on the time course of the ERP signal in our analysis framework can offer compared to the traditional analysis. PMID- 26683334 TI - A novel ATAC-seq approach reveals lineage-specific reinforcement of the open chromatin landscape via cooperation between BAF and p63. AB - BACKGROUND: Open chromatin regions are correlated with active regulatory elements in development and are dysregulated in diseases. The BAF (SWI/SNF) complex is essential for development, and has been demonstrated to remodel reconstituted chromatin in vitro and to control the accessibility of a few individual regions in vivo. However, it remains unclear where and how BAF controls the open chromatin landscape to regulate developmental processes, such as human epidermal differentiation. RESULTS: Using a novel "on-plate" ATAC-sequencing approach for profiling open chromatin landscapes with a low number of adherent cells, we demonstrate that the BAF complex is essential for maintaining 11.6 % of open chromatin regions in epidermal differentiation. These BAF-dependent open chromatin regions are highly cell-type-specific and are strongly enriched for binding sites for p63, a master epidermal transcription factor. The DNA sequences of p63 binding sites intrinsically favor nucleosome formation and are inaccessible in other cell types without p63 to prevent ectopic activation. In epidermal cells, BAF and p63 mutually recruit each other to maintain 14,853 open chromatin regions. We further demonstrate that BAF and p63 cooperatively position nucleosomes away from p63 binding sites and recruit transcriptional machinery to control tissue differentiation. CONCLUSIONS: BAF displays high specificity in controlling the open chromatin landscape during epidermal differentiation by cooperating with the master transcription factor p63 to maintain lineage-specific open chromatin regions. PMID- 26683336 TI - Phylogenomic analyses reveal a molecular signature linked to subterranean adaptation in rodents. AB - BACKGROUND: Genome-wide signatures of convergent evolution are widely expected but rarely revealed in animals. Subterranean rodent genome and transcriptome data produced by next-generation sequencing facilitate the use of phylogenetic methods to infer non-synonymous and synonymous substitution rates within coding regions, which can reveal changes at the molecular level that are correlated with the dramatic shift from a terrestrial to subterranean habitat. RESULTS: Our study used previously sequenced genome or transcriptome data of two subterranean rodents, the blind mole rat and naked mole rat, and their terrestrial relatives, the mouse and guinea pig, to investigate the genetic basis of rodent subterranean adaptation. An analysis of 4996 orthologous genes revealed that the substitution pace of coding sequences was significantly slower in the blind mole rat than in the mouse, and slower in the naked mole rat than in the guinea pig. The dN/dS ratio was significantly higher in the blind mole rat than in the mouse and in the naked mole rat than in the guinea pig. These patterns are most likely related to the longer generation time and lower effective population size of subterranean rodents caused by subterranean ecological constraints. We also identified some genes and gene ontology (GO) categories that might be candidates for adaptation to subterranean life. CONCLUSIONS: Our study reveals a case of subterranean convergent evolution in rodents that is correlated with change in the pace and mode of molecular evolution observed at the genome scale. We believe that this genomic signature could have also evolved in other cases of subterranean convergence. Additionally, the genes that displayed the most radical changes in their patterns of evolution and their associated GO categories provide a strong basis for further comparative and functional studies, and potentially reveal molecular signatures of adaptation to subterranean life. PMID- 26683338 TI - Variable Phonological Rules and 'Quantal' Perception as a Source of Probabilistic Sound Change: The Case of Intervocalic Voicing in Old Tuscan. AB - The origin and nature of 'irregular', 'sporadic' sound changes have been debated by different theories of phonological change since at least the Neogrammarians. They are often attributed to non-phonological factors, as analogy or borrowing, or to the non-(purely)-phonological mechanism of lexical diffusion. The aim of this paper is to show that an irregular sound change in the historical phonology of Tuscan - namely the voicing of some intervocalic voiceless stops - is not due to borrowing (as often argued), but to a variable and allophonic voicing rule, whose output was only partially subject to phonological recategorization. The most likely causes for this irregular outcome are the variable strength intervocalic voicing had in different environments, the interaction with another lenition process and the perceptual ambiguity of the lenited stops. PMID- 26683337 TI - Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro. AB - BACKGROUND: Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol extract of D. sophia seeds (EEDS) on human Phase I/II (DMEs) and P-glycoprotein (p-gp) in vitro. METHODS: The enzyme activities of human Phase I (cytochrome P450s, CYPs), Phase II (uridine diphosphate glucuronosyltransferases, UGTs) DMEs, and the drug transporter P-gp were determined in the presence of various concentrations of EEDS using commercially available luminogenic assay systems. The mode of enzyme inhibition and the inhibitory constant (Ki) value of EEDS were graphically determined with Lineweaver-Burk double reciprocal plots and secondary plots, respectively. RESULTS: The enzyme activity assays showed that EEDS moderately inhibited the CYP1A2, CYP2C9, and CYP2C19 isoforms with half maximal inhibitory concentrations (IC50) of 47.3, 25.8, and 38.7 MUg/mL, respectively. Graphical analyses with Lineweaver-Burk double reciprocal plots and secondary plots indicated that EEDS competitively inhibited CYP2C9 with a Ki value of 19.8 MUg/mL; however, it inhibited CYP2C9 and CYP2C19 in a mixed mode with Ki values of 5.2, and 11.9 MUg/mL, respectively. Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 MUg/mL. CONCLUSIONS: EEDS is a selective inhibitor of CYP1A2, CYP2C9, and CYP2C19 with moderate enzymatic inhibition. Clinically, full consideration should be given to a potential toxic adverse effect from a herb-drug interaction when drugs that are particularly susceptible to CYP1A2, CYP2C9, or CYP2C19-mediated metabolism are taken together with EEDS. Characterization of metabolic profiles of specific herbal drugs could help consumers and medical specialists to use them safely as a complementary and alternative medicine. PMID- 26683339 TI - Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia. AB - A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. PMID- 26683340 TI - Pancreas-specific activation of mTOR and loss of p53 induce tumors reminiscent of acinar cell carcinoma. AB - BACKGROUND: Pancreatic acinar cell carcinoma (ACC) is a rare tumor entity with an unfavorable prognosis. Recent whole-exome sequencing identified p53 mutations in a subset of human ACC. Activation of the mammalian target of rapamycin (mTOR) pathway is associated with various pancreatic neoplasms. We thus aimed at analyzing whether activation of mTOR with a concomitant loss of p53 may initiate ACC. METHODS: We generated transgenic mouse models in which mTOR was hyperactivated through pancreas-specific, homozygous tuberous sclerosis 1 (Tsc1) deficiency, with or without deletion of p53 (Tsc1 (-/-) and Tsc1 (-/-) ; p53 (-/ ) ). Activity of mTOR signaling was investigated using mouse tissues and isolated murine cell lines. Human ACC specimens were used to corroborate the findings from the transgenic mouse models. RESULTS: Hyperactive mTOR signaling in Tsc1 (-/-) mice was not oncogenic but rather induced a near-complete loss of the pancreatic acinar compartment. Acinar cells were lost as a result of apoptosis which was associated with p53 activation. Concomitantly, ductal cells were enriched. Ablation of p53 in Tsc1-deficient mice prevented acinar cell death but promoted formation of acinar cells with severe nuclear abnormalities. One out of seven Tsc1 (-/-) ; p53 (-/-) animals developed pancreatic tumors showing a distinctive tumor morphology, reminiscent of human ACC. Hyperactive mTOR signaling was also detected in a subset of human ACC. CONCLUSION: Hyperactive mTOR signaling combined with loss of p53 in mice induces tumors similar to human ACC. PMID- 26683342 TI - Nerve growth factor negatively regulates bone marrow granulopoiesis during small intestinal inflammation. PMID- 26683341 TI - Computational Models Describing Possible Mechanisms for Generation of Excessive Beta Oscillations in Parkinson's Disease. AB - In Parkinson's disease, an increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with difficulty in movement initiation. An important role in the generation of these oscillations is thought to be played by the motor cortex and by a network composed of the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe). Several alternative models have been proposed to describe the mechanisms for generation of the Parkinsonian beta oscillations. However, a recent experimental study of Tachibana and colleagues yielded results which are challenging for all published computational models of beta generation. That study investigated how the presence of beta oscillations in a primate model of Parkinson's disease is affected by blocking different connections of the STN-GPe circuit. Due to a large number of experimental conditions, the study provides strong constraints that any mechanistic model of beta generation should satisfy. In this paper we present two models consistent with the data of Tachibana et al. The first model assumes that Parkinsonian beta oscillation are generated in the cortex and the STN-GPe circuits resonates at this frequency. The second model additionally assumes that the feedback from STN GPe circuit to cortex is important for maintaining the oscillations in the network. Predictions are made about experimental evidence that is required to differentiate between the two models, both of which are able to reproduce firing rates, oscillation frequency and effects of lesions carried out by Tachibana and colleagues. Furthermore, an analysis of the models reveals how the amplitude and frequency of the generated oscillations depend on parameters. PMID- 26683343 TI - Stoner-enhanced paramagnetism in tungsten tetraboride. AB - We demonstrate that tungsten tetraboride (WB4), a heavy transition metallic compound without magnetic atoms, is an exchange-enhanced paramagnet revealed by the magnetization and specific heat measurements. WB4 has a small effective magnetic moment of 0.53 MUB/fu. The high magnetic susceptibility in the magnitude of 1 memu (mol.Oe)(-1) below 10 K obeys quadratic temperature dependence. The upturn behavior of C(P)/T versus T(2) at low temperatures is attributed to the electron-paramagnon interactions. A high Stoner enhancement parameter, Z = 0.93, was derived to explain the enhanced paramagnetism based on the Stoner model. PMID- 26683345 TI - Past and future perspectives on mathematical models of tick-borne pathogens. AB - Ticks are vectors of pathogens which are important both with respect to human health and economically. They have a complex life cycle requiring several blood meals throughout their life. These blood meals take place on different individual hosts and potentially on different host species. Their life cycle is also dependent on environmental conditions such as the temperature and habitat type. Mathematical models have been used for the more than 30 years to help us understand how tick dynamics are dependent on these environmental factors and host availability. In this paper, we review models of tick dynamics and summarize the main results. This summary is split into two parts, one which looks at tick dynamics and one which looks at tick-borne pathogens. In general, the models of tick dynamics are used to determine when the peak in tick densities is likely to occur in the year and how that changes with environmental conditions. The models of tick-borne pathogens focus more on the conditions under which the pathogen can persist and how host population densities might be manipulated to control these pathogens. In the final section of the paper, we identify gaps in the current knowledge and future modelling approaches. These include spatial models linked to environmental information and Geographic Information System maps, and development of new modelling techniques which model tick densities per host more explicitly. PMID- 26683344 TI - Association of Urinary Sodium Excretion With Blood Pressure and Cardiovascular Clinical Events in 17,033 Latin Americans. AB - BACKGROUND: Information on actual sodium intake and its relationships with blood pressure (BP) and clinical events in South America is limited. The aim of this cohort study was to assess the relationship of sodium intake with BP, cardiovascular (CV) events, and mortality in South America. METHODS: We studied 17,033 individuals, aged 35-70 years, from 4 South American countries (Argentina, Brazil, Chile, and Colombia). Measures of sodium excretion, estimated from morning fasting urine, were used as a surrogate for daily sodium intake. We measured BP and monitored the composite outcome of death and major CV events. RESULTS: Overall mean sodium excretion was 4.70+/-1.43g/day. A positive, nonuniform association between sodium and BP was detected, with a significant steeper slope for the relationship at higher sodium excretion levels (P < 0.001 for interaction). With a median follow-up of 4.7 years, the primary composite outcome (all-cause death, myocardial infarction, stroke, or heart failure) occurred in 568 participants (3.4%). Compared with sodium excretion of 5-6g/day (reference group), participants who excreted >7g/day had increased risks of the primary outcome (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.24 to 2.40; P < 0.001), as well as death from any cause (OR 1.87; 95% CI 1.23 to 2.83; P = 0.003) and major CV disease (OR 1.77; 95% CI 1.12 to 2.81; P = 0.014). Sodium excretion of <3g/day was associated with a statistically nonsignificant increased risk of the primary outcome (OR 1.20; 95% CI 0.86 to 1.65; P = 0.26) and death from any cause (OR 1.25; 95% CI 0.81 to 1.93; P = 0.29), and a significant increased risk of major CV disease (OR 1.50; 95% CI 1.01 to 2.24; P = 0.048), as compared to the reference group. CONCLUSIONS: Our results support a positive, nonuniform association between estimated urinary sodium excretion and BP, and a possible J-shaped pattern of association between sodium excretion over the entire range and clinical outcomes. PMID- 26683346 TI - Automated Discovery and Refinement of Reactive Molecular Dynamics Pathways. AB - We describe a flexible and broadly applicable energy refinement method, "nebterpolation," for identifying and characterizing the reaction events in a molecular dynamics (MD) simulation. The new method is applicable to ab initio simulations with hundreds of atoms containing complex and multimolecular reaction events. A key aspect of nebterpolation is smoothing of the reactive MD trajectory in internal coordinates to initiate the search for the reaction path on the potential energy surface. We apply nebterpolation to analyze the reaction events in an ab initio nanoreactor simulation that discovers new molecules and mechanisms, including a C-C coupling pathway for glycolaldehyde synthesis. We find that the new method, which incorporates information from the MD trajectory that connects reactants with products, produces a dramatically distinct set of minimum energy paths compared to existing approaches that start from information for the reaction end points alone. The energy refinement method described here represents a key component of an emerging simulation paradigm where molecular dynamics simulations are applied to discover the possible reaction mechanisms. PMID- 26683347 TI - Influence of Priming on Patient-Reported Outcome Measures: A Randomized Controlled Trial. AB - BACKGROUND: Patient-reported outcome measures (PROMs) are influenced by psychosocial factors, but it is unknown whether we can influence PROM scores by modifying the mindset of the patient. PURPOSE: We assessed whether priming affects scores on PROMs. METHODS: In all, 168 patients with musculoskeletal illness participated in this double-blinded, randomized, controlled, parallel study between July 2014 and October 2014 in a level I trauma center. Inclusion criteria were patients aged 18 years or older with English fluency and literacy and the ability to provide informed consent. Priming was performed by means of the Pain Catastrophizing Scale (PCS). The patients were randomized (1:1:1) into 3 groups: intervention group I was negatively primed with the original PCS; intervention group II was positively primed with a positively phrased PCS group; and control group III was not primed. Assessments were performed using PROMs on the domain of physical function, depression, and pain. Bivariate and multivariable regression analyses were conducted. RESULTS: The intervention and control groups were well balanced in demographic and condition-specific characteristics. The positive PCS was independently associated with higher PROM scores in the physical function domain (Patient-Reported Outcome Measurement Information System Upper Extremity Function: coefficient = 4.7, partial R(2) = 0.042; CI: 1.2-8.2; p < 0.010). CONCLUSIONS: Patients primed with a positively phrased version of the PCS reported less functional disability as compared with patients who were either negatively primed or not primed at all. This suggests that by influencing the mindset, PROMs can be influenced, resulting in better outcome if positively primed. LEVEL OF EVIDENCE: Level 1 therapeutic study. TRIAL REGISTRATION: NCT02209259. PMID- 26683348 TI - The Art and Science of Learning, Teaching, and Delivering Feedback in Psychosomatic Medicine. AB - BACKGROUND: The teaching and learning of psychosomatic medicine has evolved with the better understanding of effective teaching methods and feedback delivery in medicine and psychiatry. OBJECTIVES: We sought to review the variety of teaching methods used in psychosomatic medicine, to present principles of adult learning (and how these theories can be applied to students of psychosomatic medicine), and to discuss the role of effective feedback delivery in the process of teaching and learning psychosomatic medicine. METHODS: In addition to drawing on the clinical and teaching experiences of the authors of the paper, we reviewed the literature on teaching methods, adult learning theories, and effective feedback delivery methods in medicine to draw parallels for psychosomatic medicine education. RESULTS: We provide a review of teaching methods that have been employed to teach psychosomatic medicine over the past few decades. We outline examples of educational methods using the affective, behavioral, and cognitive domains. We provide examples of learning styles together with the principles of adult learning theory and how they can be applied to psychosomatic medicine learners. We discuss barriers to feedback delivery and offer suggestions as to how to give feedback to trainees on a psychosomatic medicine service. CONCLUSIONS: The art of teaching psychosomatic medicine is dynamic and will continue to evolve with advances in the field. Psychosomatic medicine educators must familiarize themselves with learning domains, learning styles, and principles of adult learning in order to be impactful. Effective feedback delivery methods are critical to fostering a robust learning environment for psychosomatic medicine. PMID- 26683349 TI - Clinical neuroanatomy, five years on: Mini-Geschwinds with fancy toys? PMID- 26683350 TI - Callistrilones A and B, Triketone-Phloroglucinol-Monoterpene Hybrids with a New Skeleton from Callistemon rigidus. AB - The first triketone-phloroglucinol-monoterpene hybrids, callistrilones A and B (1 and 2), along with a postulated biosynthetic intermediate (3) were isolated from the leaves of Callistemon rigidus. Compounds 1 and 2 featured a new carbon skeleton with an unprecedented [1]benzofuro[2,3-a]xanthene or [1]benzofuro[3,2 b]xanthene pentacyclic ring system composed of three kinds of building blocks. Their structures and absolute configurations were elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway for the new compounds is also proposed. Compound 1 exhibited moderate antibacterial activity against Gram positive bacteria including multiresistant strains. PMID- 26683351 TI - Plasma neutrophil gelatinase-associated lipocalin as a predictive biomarker for the detection of acute kidney injury in adult poisoning. AB - CONTEXT: Acute kidney injury (AKI) is a serious complication in intoxicated patients. Recently, a new biomarker - neutrophil gelatinase-associated lipocalin (NGAL) - was used to predict AKI in patients who were critically ill or had sepsis. OBJECTIVE: To evaluate the utility of plasma NGAL as an early predictor of AKI in adults with acute poisoning. MATERIALS AND METHODS: This retrospective, observational, cohort study was conducted between December 2013 and November 2014. A total of 157 consecutive adult patients who presented to the emergency department (Level 1 regional center) of Kyungpook National University Hospital, a tertiary teaching hospital in Daegu, Korea, within 24 h of poisoning were included. Initial plasma NGAL levels and laboratory parameters were concurrently measured upon hospital arrival. AKI was defined according to Acute Kidney Injury Network criteria. Development of AKI was predicted using plasma NGAL levels and by analyzing the area under the receiver operating characteristic curve (AUC). RESULTS: The overall rate of AKI was 14.6% (n = 23). Plasma NGAL levels in the AKI group were higher than those in the non-AKI group (median, 310 vs. 86 ng/mL; p < 0.001). Additionally, baseline NGAL levels allowed for better prediction of AKI than initial creatinine levels. The AUC of plasma NGAL was 0.895 (95% confidence interval [CI]: 0.832-0.941), with a cut-off value of 227 ng/mL (sensitivity, 76.2%; specificity, 95.8%). Plasma NGAL had a higher predictive capacity for AKI than serum creatinine (AUC 0.741, 95% CI: 0.662-0.810), base deficit (AUC 0.795, 95% CI: 0.701-0.870), lactate (AUC 0.781, 95% CI: 0.690 0.856), and anion gap (AUC 0.636, 95% CI: 0.535-0.730). CONCLUSION: Plasma NGAL may serve as a good predictor of AKI in cases of adult poisoning. PMID- 26683352 TI - Paramagnetic Nanoparticles Leave Their Mark on Nuclear Spins of Transiently Adsorbed Proteins. AB - The successful application of nanomaterials in biosciences necessitates an in depth understanding of how they interface with biomolecules. Transient associations of proteins with nanoparticles (NPs) are accessible by solution NMR spectroscopy, albeit with some limitations. The incorporation of paramagnetic centers into NPs offers new opportunities to explore bio-nano interfaces. We propose NMR paramagnetic relaxation enhancement as a new tool to detect NP binding surfaces on proteins with increased sensitivity, also extending the applicability of NMR investigations to heterogeneous biomolecular mixtures. The adsorption of ubiquitin on gadolinium-doped fluoride-based NPs produced residue specific NMR line-broadening effects mapping to a contiguous area on the surface of the protein. Importantly, an identical paramagnetic fingerprint was observed in the presence of a competing protein-protein association equilibrium, exemplifying possible interactions taking place in crowded biological media. The interaction was further characterized using isothermal titration calorimetry and upconversion emission measurements. The data indicate that the used fluoride based NPs are not biologically inert but rather are capable of biomolecular recognition. PMID- 26683353 TI - Biochemical and inflammatory aspects in patients with severe sepsis and septic shock: The predictive role of IL-18 in mortality. AB - BACKGROUND: Sepsis is a major health care problem, with a significant mortality rate in intensive care units. We evaluated biochemical and inflammatory markers in patients with severe sepsis and septic shock and its association of with mortality rates. METHODS: Critically ill patients with diagnoses of sepsis - severe sepsis group (n=23) and septic shock group (n=25), and a control group (n=17) were recruited within 24h of entry into the ICU. Serum levels of inflammatory mediators were measured (IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, IL 18 and nitric oxide). We have also collected clinical parameters and laboratorial tests to estimate severity and organ dysfunction (APACHE II, SOFA, lactate). These results were compared between survivors and no survivors. RESULTS: IL-18 was directly related to mortality independently of other inflammatory mediators, especially IL-1beta, although the inflammatory pathway is closely linked to inflammasome activation and both have simultaneous release in the infectious process. Mortality was directly proportional to IL-18 plasma levels, which did not occur with other inflammatory mediators. CONCLUSIONS: IL-18 is an important predictor of mortality in humans with both severe sepsis and septic shock, independent of IL-1beta. PMID- 26683354 TI - A novel peptide adropin in cardiovascular diseases. AB - Cardiovascular diseases, such as atherosclerosis and hypertension, are the major cause of mortality and morbidity in the world. Adropin was first discovered in 2008 by Kumar and his coworkers. Adropin, encoded by the Energy Homeostasis Associated gene, is expressed in many tissues and organs, such as pancreatic tissue, liver, brain, kidney, endocardium, myocardium, and epicardium. In this review, we have summarized recent data suggesting the roles of adropin in several major cardiovascular diseases. Increasing evidence suggests that adropin is a potential regulator of cardiovascular functions and plays a protective role in the pathogenesis and development of cardiovascular diseases. However, further studies are needed to elucidate the specific mechanisms underlying the association between adropin and cardiovascular diseases. PMID- 26683355 TI - Diiodothyropropionic acid (DITPA) cross-reacts with thyroid function assays on different immunoassay platforms. PMID- 26683357 TI - Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib. AB - Proteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type. PMID- 26683358 TI - Diabetes mellitus and the risk of glioma: a meta-analysis. AB - Some studies reported a statistically significant inverse association between diabetes mellitus (DM) and risk of gliomas. However, the result is still controversial. We thus did a meta-analysis and summarized the evidence on the incidence of gliomas that has been studied in its association with DM. Seven case control studies and 4 cohort studies were selected in this meta-analysis (n = 5898251). DM was significantly associated with decreased risk of gliomas (OR = 0.79; 95% CI 0.67 - 0.93; P = 0.004; I2 = 59%). In the subgroup analysis of race, Caucasians of DM showed decreased risk of gliomas (OR = 0.81; 95% CI 0.69 - 0.94; P = 0.007). In the subgroup analysis of design, a statistically significant protective effect of DM on gliomas was observed in case-control studies (OR = 0.68; 95 % CI, 0.53-0.87; P = 0.002), while no such effect was observed in cohort studies (OR = 0.97; 95 % CI, 0.83-1.13; P = 0.70). In a further stratified analysis by gender, a significant association was found among males with DM (OR = 0.83; 95 % CI, 0.70-0.99; P = 0.04). No significant association was found between females with DM and gliomas (OR = 0.97; 95 % CI, 0.78-1.21; P = 0.81). In summary, this meta-analysis of current evidence suggests that DM is significantly associated with decreased gliomas risk in Caucasian and males. PMID- 26683359 TI - Genome-wide profiling of DNA methylation and gene expression in esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide. Previous studies have suggested that DNA methylation involved in the development of ESCC. However, the precise mechanisms underlying the regulation and maintenance of the methylome as well as their relationship with ESCC remain poorly understood. Herein, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and RNA-Seq to investigate whole-genome DNA methylation patterns and the genome expression profiles in ESCC samples. The results of MeDIP Seq analyses identified differentially methylated regions (DMRs) covering almost the entire genome with sufficient depth and high resolution. The gene ontology (GO) analysis showed that the DMRs related genes belonged to several different ontological domains, such as cell cycle, adhesion, proliferation and apoptosis. The RNA-Seq analysis identified a total of 6150 differentially expressed genes (3423 up-regulated and 2727 down-regulated). The significant GO terms showed that these genes belonged to several molecular functions and biological pathways. Moreover, the bisulfite-sequencing of genes MLH1, CDH5, TWIST1 and CDX1 confirmed the methylation status identified by MeDIP-Seq. And the mRNA expression levels of MLH1, TWIST1 and CDX1 were consistent with their DNA methylation profiles. The DMR region of MLH1 was found to correlate with survival. The identification of whole-genome DNA methylation patterns and gene expression profiles in ESCC provides new insight into the carcinogenesis of ESCC and represents a promising avenue through which to investigate novel therapeutic targets. PMID- 26683360 TI - Emodin potentiates the antiproliferative effect of interferon alpha/beta by activation of JAK/STAT pathway signaling through inhibition of the 26S proteasome. AB - The 26S proteasome is a negative regulator of type I interferon (IFN-alpha/beta) signaling. Inhibition of the 26S proteasome by small molecules may be a new strategy to enhance the efficacy of type I IFNs and reduce their side effects. Using cell-based screening assay for new 26S proteasome inhibitors, we found that emodin, a natural anthraquinone, was a potent inhibitor of the human 26S proteasome. Emodin preferably inhibited the caspase-like and chymotrypsin-like activities of the human 26S proteasome and increased the ubiquitination of endogenous proteins in cells. Computational modeling showed that emodin exhibited an orientation/conformation favorable to nucleophilic attack in the active pocket of the beta1, beta2, and beta5 subunits of the 26S proteasome. Emodin increased phosphorylation of STAT1, decreased phosphorylation of STAT3 and increased endogenous gene expression stimulated by IFN-alpha. Emodin inhibited IFN-alpha stimulated ubiquitination and degradation of type I interferon receptor 1 (IFNAR1). Emodin also sensitized the antiproliferative effect of IFN-alpha in HeLa cervical carcinoma cells and reduced tumor growth in Huh7 hepatocellular carcinoma-bearing mice. These results suggest that emodin potentiates the antiproliferative effect of IFN-alpha by activation of JAK/STAT pathway signaling through inhibition of 26S proteasome-stimulated IFNAR1 degradation. Therefore, emodin warrants further investigation as a new means to enhance the efficacy of IFN-alpha/beta. PMID- 26683362 TI - KIM-1/TIM-1 in proximal tubular cell immune response. PMID- 26683361 TI - The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. AB - Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines (PE01 and PE04 models) and a xenograft model (OV1002) were measured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but not in the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, gammaH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by gammaH2AX, and interfered with the activation of DNA damage response induced by cisplatin. Furthermore, HDAC2 depletion affected gammaH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin, and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting expression of HDAC2, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy, and implicate HDAC2 in higher order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo. PMID- 26683363 TI - The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells. AB - Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts for identification of safer and more effective metformin mimetic compounds. The plant Ficus microcarpa is widely used for the treatment of type 2 diabetes in traditional medicine in South Asia. We obtained extracts from this plant and identified a small molecule, plectranthoic acid (PA), with potent 5'AMP-activated kinase (AMPK) activating properties far superior than metformin. AMPK is the central hub of metabolic regulation and a well-studied therapeutic target for metabolic syndrome, type-2 diabetes and cancer. We observed that treatment of prostate cancer (PCa) cells with PA inhibited proliferation and induced G0/G1 phase cell cycle arrest that was associated with up-regulation of cyclin kinase inhibitors p21/CIP1 and p27/KIP1. PA treatment suppressed mTOR/S6K signaling and induced apoptosis in PCa cells in an AMPK-dependent manner. Interestingly, PA-induced autophagy in PCa cells was found to be independent of AMPK activation. Combination studies of PA and metformin demonstrated that metformin had an inhibitory effect on PA-induced AMPK activation and suppressed PA-mediated apoptosis. Given the anti-proliferative role of PA in cancer and its potent anti-hyperglycemic activity, we suggest that PA should be explored further as a novel activator of AMPK for its ultimate use for the prevention of cancers and treatment of type 2 diabetes. PMID- 26683364 TI - Whole-exome tumor sequencing study in biliary cancer patients with a response to MEK inhibitors. AB - We previously conducted a phase-II study with selumetinib (AZD6244), a small molecule inhibitor of MEK1/2, in advanced biliary tract cancers (BTC), where the primary endpoint was response rate. Several patients experienced objective response. These findings were confirmed with MEK162 in a similar patient population. To assess for tumor-specific genetic variants that mediate sensitivity to MEK inhibition in BTC, we performed whole-exome sequencing in patients with an objective response to selumetinib. Normal and tumor DNA from FFPE tissue from two patients who experienced an objective response underwent whole-exome sequencing. Raw sequence reads were processed with GATK workflow and tumor specific variants were identified using MuTect and VarScan2. Ensemble Variant Effect Predictor was used to determine functional consequences of these variants. Copy number changes and potential gene fusion events were also screened. Findings were compared to assess for any commonality between the two tumor samples, and whether the identified variants were intrinsic to the MAPK pathway. 1169 and 628 tumor-specific variants were identified in the two samples. Further analysis demonstrated 60 and 53 functional and novel variants, respectively. Of the identified tumor-specific variants, fusion events or copy number changes, no commonality was seen. Several variants in genes associated with ERK signaling were present in each tumor sample. Although there were no common tumor-specific variants in the two patients who exhibited an objective response to selumetinib, several genes associated with ERK signaling were identified. Confirmatory studies investigating the role of the identified genes and other potential tumor independent factors need further investigation. PMID- 26683366 TI - Effect of Co-Ordination Chemistry and Oxidation State on the (207)Pb Magnetic Shielding Tensor: A DFT/ZORA Investigation. AB - The magnetic shielding tensor of (207)Pb is calculated for various solids exhibiting (1) a holodirected lead(II) center containing a stereochemically inactive lone pair, (2) a hemidirected lead(II) center with a stereochemically active lone-pair, or (3) a lead(IV) center. Tensors investigated at the scalar relativistic level are compared with those calculated with the full ZORA/spin orbit Hamiltonian. The effect of using GGA density functionals is compared to the use of hybrid density functionals. PMID- 26683365 TI - Protein kinase D2 contributes to TNF-alpha-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3beta/beta-catenin pathway in hepatocellular carcinoma. AB - Although protein kinase D (PKD) has been shown to contribute to invasion and metastasis in several types of cancer, the role of PKD in the epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) has remained unclear. We found that PKD2 is up-regulated in HCC and is correlated with the metastasis of HCC. PKD2 positively regulated TNF-alpha-induced EMT and metastasis of HCC. Mechanistic studies revealed TNF-alpha-induced PKD2 activation is mediated by the formation of a TNFR1/TRAF2 complex. PKD2 bound directly to the p110alpha and p85 subunits of PI3K and promoted the PI3K/Akt/GSK-3beta signaling cascade to stimulate EMT. In conclusion, our results have uncovered a novel role for the regulation of EMT and suggest inhibition of PKD2 as a potential therapeutic strategy for HCC. PMID- 26683367 TI - Modified Grice-Green subtalar arthrodesis performed using a partial fibular graft yields satisfactory results in patients with cerebral palsy. AB - The aim of this study was to report the experience with the use of a modified Grice-Green technique, which was performed using a partial subperiosteal fibular bone graft because of valgus unstable foot in children with cerebral palsy. Fifteen feet of 11 patients were evaluated on the basis of the appearance of the feet, clinical symptoms, and radiographic measurements. After an average follow up duration of 24 (9-39) months, all feet showed satisfactory clinical and radiological results. Solid fusion and sustained correction took place in all feet. The gap at the donor site was bridged with new bone in all cases. No donor site morbidity was detected. This modification of the Grice-Green technique can be used effectively in the correction of planovalgus foot in cerebral palsy. PMID- 26683368 TI - Long-term results of Galeazzi-equivalent injuries in adolescents--open reduction and internal fixation of the ulna. AB - We diagnosed 10 Galeazzi-equivalent injuries. We report the radiological and clinical results at the end of growth in adolescents, including the results of ulnar lengthening. This study included 10 Galeazzi-equivalent injuries (seven patients requiring open reduction and three requiring closed reduction for ulnar lesions) seen since 2004. The periosteum was entrapped around the fractured physis in five patients and the extensor carpi ulnaris to the periosteum was interposed in two patients. Among the seven patients, ulnar lengthening was performed in only three patients. Ulnar variances at the time of the lengthening were -6, -6, and -5 mm. Gradual lengthening was performed. Radiologic abnormalities, including the ulnar variances, were investigated at the end of growth. In addition, pain scores, the range of wrist motion, and grip strength were evaluated and compared with nonlengthened ulnas. The mean age of the patients at the final follow-up was 19.7 years, and the mean total follow-up period was 6 years. The final ulnar variances were -5, -5, -3, and 0 mm in four patients with nonlengthened ulnas among the seven patients. Three patients with lengthened ulnas showed final neutral variances. In four nonlengthened ulnas, three ulnas bowed to the radial side and two ulnar heads had an inclined and deformed shape. Joint mismatch of the distal radioulnar joint surface was found in one patient with lengthened and one with nonlengthened ulnas. Three patients with nonlengthened ulnas showed decreased range of wrist motions. Comparison of contralateral grip strength indicated a significant difference between patients with or without lengthened ulnas. Long-term follow-up after Galeazzi-equivalent injuries may be essential to check for premature epiphyseal closure, length discrepancies, or joint incongruency. A procedure for a shortened ulna could be needed; however, the appropriate time and degree of lengthening remain to be investigated. PMID- 26683369 TI - Early prediction of outcomes in hip fractures: initial fracture displacement. AB - We retrospectively analyzed the surgical treatment of 28 pediatric hip fractures. The majority of cases were Delbet type 2 (57%) and type 3 (29%). The average age of the patients was 10.8 years (range: 2-16 years). The mean follow-up period was 91 months. Displaced fractures were found in 18 cases (64%). The major factor in the development of avascular necrosis was the degree of displacement at the time of initial presentation (P<0.05), irrespective of fracture type. Although the degree of initial displacement cannot be prevented, careful exposure of soft tissue during open reduction will reduce avascular necrosis. PMID- 26683370 TI - Modified Ponseti method of treatment for correction of neglected clubfoot in older children and adolescents--a preliminary report. AB - Congenital talipes equinovarus may be the most common congenital orthopedic condition requiring treatment. Nonoperative treatment including different methods is generally accepted as the first step in the deformity correction. Ignacio Ponseti introduced his nonsurgical approach to the treatment of clubfoot in the early 1940s. The method is reportedly successful in treating clubfoot in patients up to 9 years of age. However, whether age at the beginning of treatment affects the rate of effective correction and relapse is unknown. We have applied the Ponseti method successfully with some modifications for 11 patients with a mean age of 11.2 years (range, 6 to 19 years) with neglected and untreated clubbed feet. The mean follow-up was 15 months (12 to 36 months). Correction was achieved with a mean of nine casts (six to 13). Clinically, 17 out of 18 feet (94.4%) were considered to achieve a good result with no need for further surgery. The application of this method of treatment is very simple and also cheap in developing countries with limited financial and social resources for health service. To the best of the authors' knowledge, such a modified method as a correction method for clubfoot in older children and adolescents has not been applied previously for neglected clubfeet in older children in the literature. PMID- 26683371 TI - A new predictive indicator by arthrography for future acetabular growth following conservative treatment of developmental dysplasia of the hip. AB - The aim of this study was to find a new predictive indicator for acetabular growth of developmental dysplasia of the hip. Seventy-three hips that were diagnosed with developmental dysplasia of the hip and treated by conservative reduction were included in our study. In 30 hips with center-edge angle <= 10 degrees at age 4, the center-edge of the acetabular limbus angle (CEALA) in the arthrogram was measured. On the basis of the results, CEALA was significantly smaller in the secondary acetabular dysplasia group than in the normal group at maturity. In conclusion, CEALA is a more reliable and accurate predictive indicator for acetabular development than center-edge angle or acetabular index. PMID- 26683372 TI - Developmental Defects of Caenorhabditis elegans Lacking Branched-chain alpha Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency. AB - Branched-chain alpha-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. PMID- 26683373 TI - Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility. AB - The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI) anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. "Knocking out" PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro PrP to filamin A contributes to enhanced tumor cell motility. PMID- 26683374 TI - The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency Granulopoiesis. AB - Emergency granulopoiesis occurs in response to infectious or inflammatory challenge and is a component of the innate immune response. Some molecular events involved in initiating emergency granulopoiesis are known, but termination of this process is less well defined. In this study, we found that the interferon consensus sequence binding protein (Icsbp/Irf8) was required to terminate emergency granulopoiesis. Icsbp is an interferon regulatory transcription factor with leukemia suppressor activity. Expression of Icsbp is decreased in chronic myeloid leukemia, and Icsbp(-/-) mice exhibit progressive granulocytosis with evolution to blast crisis, similar to the course of human chronic myeloid leukemia. In this study, we found aberrantly sustained granulocyte production in Icsbp(-/-) mice after stimulation of an emergency granulopoiesis response. Icsbp represses transcription of the genes encoding Fas-associated phosphatase 1 (Fap1) and growth arrest-specific 2 (Gas2) and activates genes encoding Fanconi C and F. After stimulation of emergency granulopoiesis, we found increased and sustained expression of Fap1 and Gas2 in bone marrow myeloid progenitor cells from Icsbp(-/ ) mice in comparison with the wild type. This was associated with resistance to Fas-induced apoptosis and increased beta-catenin activity in these cells. We also found that repeated episodes of emergency granulopoiesis accelerated progression to acute myeloid leukemia in Icsbp(-/-) mice. This was associated with impaired Fanconi C and F expression and increased sensitivity to DNA damage in bone marrow myeloid progenitors. Our results suggest that impaired Icsbp expression enhances leukemogenesis by deregulating processes that normally limit granulocyte expansion during the innate immune response. PMID- 26683375 TI - Crystal Structure of the CTP1L Endolysin Reveals How Its Activity Is Regulated by a Secondary Translation Product. AB - Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections. PMID- 26683376 TI - Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. AB - Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, quantitative PCR, and Western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers were increased in isolated smooth muscle cells cultured under high compared with low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization, and myocardin-related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility. PMID- 26683378 TI - Difference between central and peripheral blood pressure in healthy and hypertension-complicated pregnancy. AB - OBJECTIVE: Hemodynamics of a pregnant woman differ and change over time depending on the age of gestation. In the general population, brachial-aortic systolic pressure (SBP-AoSP) difference is known and discussed, whereas in pregnancy, it is not established. On the basis of theoretical premises it is probably different and changes with time of gestation. As AoSP is more relevant for internal organs, also for placental perfusion, and still not widely available in clinical practice, knowledge of the average SBP-AoSP difference in a healthy and complicated pregnancy could be of additional value for the management of pregnancy hypertension. The aim of this study was to assess the SBP-AoSP difference in healthy and hypertensive pregnancies in comparison with nonpregnant controls. PARTICIPANTS AND METHODS: Aortic blood pressure with applanation tonometry and brachial blood pressure under standardized conditions were measured monthly and once postpartum in 36 normotensive pregnant women (age: 29.6+/-4.8 years) and compared with 25 hypertensive pregnancies (age: 30.5+/-5.4 years) before antihypertensive treatment implementation and with 25 nonpregnant controls (age: 30.2+/-5.5 years). RESULTS: In hypertensive pregnancies, the SBP-AoSP difference was smaller throughout the entire pregnancy than in healthy pregnancies (in the second and third trimester: 14.44 vs. 15.7 mmHg, P=0.002, and 12.9 vs. 14 mmHg, P=0.02), and smaller than that in nonpregnant controls (14.88 mmHg, for third trimester, P=0.036). Comparison of healthy pregnancy and controls showed an insignificant increase in SBP-AoSP difference in the first and second trimester, whereas in the third trimester, because of a larger increase of AoSP, the SBP-AoSP difference was smaller than that in nonpregnant controls (14.66 mmHg, P>0.05). CONCLUSION: A reduced SBP-AoSP difference was found in hypertensive pregnancies compared with healthy controls, which may signify a narrower safety margin for complications. Comparison of pregnant women with nonpregnant controls showed that a significant difference for the SBP-AoSP difference was present only for the postpartum period. PMID- 26683377 TI - Dimethyl Fumarate Inhibits the Nuclear Factor kappaB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein. AB - In breast tumors, activation of the nuclear factor kappaB (NFkappaB) pathway promotes survival, migration, invasion, angiogenesis, stem cell-like properties, and resistance to therapy--all phenotypes of aggressive disease where therapy options remain limited. Adding an anti-inflammatory/anti-NFkappaB agent to breast cancer treatment would be beneficial, but no such drug is approved as either a monotherapy or adjuvant therapy. To address this need, we examined whether dimethyl fumarate (DMF), an anti-inflammatory drug already in clinical use for multiple sclerosis, can inhibit the NFkappaB pathway. We found that DMF effectively blocks NFkappaB activity in multiple breast cancer cell lines and abrogates NFkappaB-dependent mammosphere formation, indicating that DMF has anti cancer stem cell properties. In addition, DMF inhibits cell proliferation and significantly impairs xenograft tumor growth. Mechanistically, DMF prevents p65 nuclear translocation and attenuates its DNA binding activity but has no effect on upstream proteins in the NFkappaB pathway. Dimethyl succinate, the inactive analog of DMF that lacks the electrophilic double bond of fumarate, is unable to inhibit NFkappaB activity. Also, the cell-permeable thiol N-acetyl l-cysteine, reverses DMF inhibition of the NFkappaB pathway, supporting the notion that the electrophile, DMF, acts via covalent modification. To determine whether DMF interacts directly with p65, we synthesized and used a novel chemical probe of DMF by incorporating an alkyne functionality and found that DMF covalently modifies p65, with cysteine 38 being essential for the activity of DMF. These results establish DMF as an NFkappaB inhibitor with anti-tumor activity that may add therapeutic value in the treatment of aggressive breast cancers. PMID- 26683379 TI - Associations between cystatin C-based eGFR, ambulatory blood pressure parameters, and in-clinic versus ambulatory blood pressure agreement in older community living adults. AB - OBJECTIVES: The objective of this study was to determine the relationship between chronic kidney disease [CKD; measured using cystatin C-based estimated glomerular filtration rate (eGFR)] and abnormal ambulatory blood pressure (including nocturnal dipping) in healthy older adults. Further, this study aimed to assess the agreement between clinic and ambulatory blood pressure monitoring. METHODS: Serum cystatin C levels were measured to calculate eGFR. Participants underwent clinic and 24-h ambulatory blood pressure measurements. Multiple linear regression was performed to examine the association between reduced cystatin C based eGFR (CKDcys) and blood pressure parameters. Bland-Altman analysis was carried out to evaluate the agreement between clinic and ambulatory measurements. RESULTS: The average age was 72 years. There were 60 individuals with CKDcys (eGFR<60 ml/min/1.73 m). Compared with those without CKDcys, individuals with CKDcys were older, more likely to have hypertension, and less likely to have normal dipping patterns. On multivariate analysis, the presence of CKDcys was found to be significantly associated with a lower mean ambulatory diastolic blood pressure (-2 mmHg, P=0.048), but not with nocturnal dipping or other blood pressure parameters. Clinic systolic blood pressure (SBP) significantly overestimated the mean wake-time ambulatory SBP; the mean difference was 11 mmHg for those without CKDcys (95% limits of agreement -14 to 35 mmHg) and 14 mmHg for those with CKDcys (95% limits of agreement -13 to 41 mmHg); there was no statistically significant effect modification by CKD status. CONCLUSION: In older, seemingly healthy adults, mild CKD was associated with lower ambulatory diastolic blood pressure. The presence of CKD did not affect interpretation of clinic versus ambulatory blood pressure monitoring, although the accuracy of clinic SBP was poor. PMID- 26683380 TI - Circadian rhythms in blood pressure, heart rate, hormones, and on polysomnographic parameters in severe obstructive sleep apnea syndrome patients: effect of continuous positive airway pressure. AB - INTRODUCTION: Seventeen male patients with severe obstructive sleep apnea syndrome (OSAS; apnea-hypopnea index>30/h) were monitored by polysomnography in the sleep lab before and after about 8 weeks of continuous positive airway pressure (CPAP). Twelve of the patients were hypertensive, but treated by antihypertensive drugs. The circadian rhythms in blood pressure (BP) and heart rate were determined by ambulatory BP monitoring and motor activity was monitored by a motion logger. As the sympathetic tone is reported to be increased in sleep apnea, the circadian rhythm in plasma norepinephrine was studied in parallel and as a marker rhythm of the biological clock plasma melatonin was determined around the clock by radioimmunoassay. RESULTS: Level and rhythm in BP and heart rate were not significantly affected by CPAP in this group of patients, but the number of dippers increased after CPAP intervention. The high 24 h plasma values of norepinephrine were lowered by CPAP therapy. In contrast, melatonin values were disturbed in OSAS patients with a loss in nocturnal increase; this pattern was not corrected by CPAP. Sleep functions (deep sleep, slow wave sleep, rapid eye movement sleep, arousal index, apnea-hypopnea index, desaturation index) were disturbed in OSAS patients as monitored by polysomnography and were significantly improved by CPAP therapy. CONCLUSION: The study indicates that BP-controlled hypertensive patients with OSAS can additionally benefit from CPAP therapy by increasing the number of dippers. This treatment significantly improved sleep functions and OSAS symptoms. In addition, arousal movements at night were also reduced and the high sympathetic tone during early morning hours was also decreased. However, there is still an indication of a disturbed function of the biological clock as the loss in the rhythm in plasma melatonin was not corrected by CPAP. PMID- 26683381 TI - Validation of the Microlife BP A200 Comfort and W2 Slim automated blood pressure monitors in a general adult population according to the European Society of Hypertension and the ANSI/AAMI/ISO 81060-2: 2013 protocols. AB - OBJECTIVE: This study aimed to determine the accuracy of the Microlife BP A200 Comfort and W2 Slim automated blood pressure monitors according to the European Society of Hypertension International Protocol revision 2010 and the ANSI/AAMI/ISO 81060-2:2013 protocols. METHODS: The devices were assessed on 33 participants according to the European Society of Hypertension requirements and were then tested on 85 participants according to the ANSI/AAMI/ISO 81060-2:2013 criteria. Procedures and data analysis were carried out following protocol guidelines precisely. RESULTS: The Microlife BP A200 Comfort and W2 Slim devices passed the criteria of the European Society of Hypertension International Protocol revision 2010 for both systolic blood pressure and diastolic blood pressure. The devices also fulfilled the ANSI/AAMI/ISO 81060-2:2013 criteria, with mean differences of SBP and DPB between the devices and observers of 0.38+/ 5.12 and 0.28+/-4.29 mmHg for the BP A200 Comfort and 1.01+/-6.80 and 0.34+/-5.62 mmHg for the W2 Slim, respectively. CONCLUSION: The Microlife BP A200 Comfort and W2 Slim automated blood pressure monitors fulfilled the European Society of Hypertension revision 2010 and the ANSI/AAMI/ISO 81060-2:2013 protocols, and can be recommended for self-measurement in the general population. PMID- 26683382 TI - The use of ambulatory blood pressure monitoring to confirm a diagnosis of high blood pressure by primary-care physicians in Oregon. AB - BACKGROUND: Hypertension is the most commonly diagnosed medical condition in the USA. Unfortunately, patients are misdiagnosed in primary care because of inaccurate office-based blood pressure measurements. Several US healthcare organizations currently recommend confirming an office-based hypertension diagnosis with ambulatory blood pressure monitoring to avoid overtreatment; however, its use for the purpose of confirming an office-based hypertension diagnosis is relatively unknown. METHODS: This descriptive study surveyed 143 primary-care physicians in Oregon with regard to their current use of ambulatory blood pressure monitoring. RESULTS: Nineteen percent of the physicians reported that they would use ambulatory blood pressure monitoring to confirm an office based hypertension diagnosis, although over half had never ordered it. The most frequent indication for ordering ambulatory blood pressure monitoring was to investigate suspected white-coat hypertension (37.3%). In addition, many of the practices did not own an ambulatory blood pressure monitoring device (79.7%) and, therefore, had to refer patients to other clinics or departments for testing. CONCLUSION: Many primary-care physicians will need to change their current clinical practice to align with the shift toward a confirmation process for office-based hypertension diagnoses to improve population health. PMID- 26683384 TI - Preservation of episodic memory in semantic dementia: The importance of regions beyond the medial temporal lobes. AB - Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippocampus. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippocampus, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippocampal and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry. PMID- 26683383 TI - Horizontal tuning for faces originates in high-level Fusiform Face Area. AB - Recent work indicates that the specialization of face visual perception relies on the privileged processing of horizontal angles of facial information. This suggests that stimulus properties assumed to be fully resolved in primary visual cortex (V1; e.g., orientation) in fact determine human vision until high-level stages of processing. To address this hypothesis, the present fMRI study explored the orientation sensitivity of V1 and high-level face-specialized ventral regions such as the Occipital Face Area (OFA) and Fusiform Face Area (FFA) to different angles of face information. Participants viewed face images filtered to retain information at horizontal, vertical or oblique angles. Filtered images were viewed upright, inverted and (phase-)scrambled. FFA responded most strongly to the horizontal range of upright face information; its activation pattern reliably separated horizontal from oblique ranges, but only when faces were upright. Moreover, activation patterns induced in the right FFA and the OFA by upright and inverted faces could only be separated based on horizontal information. This indicates that the specialized processing of upright face information in the OFA and FFA essentially relies on the encoding of horizontal facial cues. This pattern was not passively inherited from V1, which was found to respond less strongly to horizontal than other orientations likely due to adaptive whitening. Moreover, we found that orientation decoding accuracy in V1 was impaired for stimuli containing no meaningful shape. By showing that primary coding in V1 is influenced by high-order stimulus structure and that high-level processing is tuned to selective ranges of primary information, the present work suggests that primary and high-level levels of the visual system interact in order to modulate the processing of certain ranges of primary information depending on their relevance with respect to the stimulus and task at hand. PMID- 26683385 TI - Event-related fMRI studies of false memory: An Activation Likelihood Estimation meta-analysis. AB - Over the last two decades, a wealth of research in the domain of episodic memory has focused on understanding the neural correlates mediating false memories, or memories for events that never happened. While several recent qualitative reviews have attempted to synthesize this literature, methodological differences amongst the empirical studies and a focus on only a sub-set of the findings has limited broader conclusions regarding the neural mechanisms underlying false memories. The current study performed a voxel-wise quantitative meta-analysis using activation likelihood estimation to investigate commonalities within the functional magnetic resonance imaging (fMRI) literature studying false memory. The results were broken down by memory phase (encoding, retrieval), as well as sub-analyses looking at differences in baseline (hit, correct rejection), memoranda (verbal, semantic), and experimental paradigm (e.g., semantic relatedness and perceptual relatedness) within retrieval. Concordance maps identified significant overlap across studies for each analysis. Several regions were identified in the general false retrieval analysis as well as multiple sub analyses, indicating their ubiquitous, yet critical role in false retrieval (medial superior frontal gyrus, left precentral gyrus, left inferior parietal cortex). Additionally, several regions showed baseline- and paradigm-specific effects (hit/perceptual relatedness: inferior and middle occipital gyrus; CRs: bilateral inferior parietal cortex, precuneus, left caudate). With respect to encoding, analyses showed common activity in the left middle temporal gyrus and anterior cingulate cortex. No analysis identified a common cluster of activation in the medial temporal lobe. PMID- 26683386 TI - Towards theory integration: Threshold model as a link between signal detection theory, fast-and-frugal trees and evidence accumulation theory. AB - RATIONALE, AIMS AND OBJECTIVES: Theories of decision making are divided between those aiming to help decision makers in the real, 'large' world and those who study decisions in idealized 'small' world settings. For the most part, these large- and small-world decision theories remain disconnected. METHODS: We linked the small-world decision theoretic concepts of signal detection theory (SDT) and evidence accumulation theory (EAT) to the threshold model and the large world of heuristic decision making that rely on fast-and-frugal decision trees (FFT). RESULTS: We connected these large- and small-world theories by demonstrating that seemingly different decision-making concepts are actually equivalent. In doing so, we were able (1) to link the threshold model to EAT and FFT, thereby creating decision criteria that take into account both the classification accuracy of FFT and the consequences built in the threshold model; (2) to demonstrate how threshold criteria can be used as a strategy for optimal selection of cues when constructing FFT; and (3) to show that the compensatory strategy expressed in the threshold model can be linked to a non-compensatory FFT approach to decision making. We also showed how construction and performance of FFT depend on having reliable information - the results were highly sensitive to the estimates of benefits and harms of health interventions. We illustrate the practical usefulness of our analysis by describing an FFT we developed for prescribing statins for primary prevention of cardiovascular disease. CONCLUSIONS: By linking SDT and EAT to the compensatory threshold model and to non-compensatory heuristic decision making (FFT), we showed how these two decision strategies are ultimately linked within a broader theoretical framework and thereby respond to calls for integrating decision theory paradigms. PMID- 26683387 TI - Surgery for Stage IIIA Non-Small-cell Lung Cancer: Lack of Predictive and Prognostic Factors Identifying Any Subgroup of Patients Benefiting From It. AB - Although a trimodality regimen for patients with stage IIIA/pN2 non-small-cell lung cancer (NSCLC) has been variably used owing to limited evidence for its benefits, it remains unknown whether any patient subgroup actually receives benefit from such an approach. To explore this question, the published data were reviewed from 1990 to 2015 to identify the possible predictors and prognosticators in this setting. Overall survival was the endpoint of our study. Of 27 identified studies, none had studied the predictors of improved outcomes with trimodality treatment. Of the potential patient- and tumor-related prognosticators, age, gender, and histologic type were the most frequently formally explored. However, none of the 3 was found to influence overall survival. The most prominent finding of the present review was the substantial lack of data supporting a trimodality treatment approach in any patient subgroup. As demonstrated in completed prospective randomized studies, the use of surgery for stage IIIA NSCLC should be limited to well-defined clinical trials. PMID- 26683388 TI - Novel single nucleotide polymorphisms (SNPs) of CYP2W1 gene in Chinese Uygur and Han populations. AB - Cytochrome P450 2W1 (CYP2W1) is expressed specially in certain cancers and could metabolize some substances into cytotoxic antitumor drugs in Caucasian ethnic population. To investigate the genetic polymorphism of CYP2W1 in Chinese, all the nine exons and exon-intron junctions were sequenced by dideoxy chain termination method among 385 Chinese subjects (including 223 Han and 162 Uygur). The present results showed that 40 single nucleotide polymorphisms (SNPs) were detected (14 in the exons and 26 in the introns), 10 were novel variants of which in Chinese. There were 7 novel SNPs in the exons and other 3 novel SNPs in the introns. Four of the 6 novel non-synonymous variations in exons, 131T > C (Leu44Pro), 1289C > A (Ala88Glu), 2027G > A (Arg187Gln) and 5070C > T (Thr383Met) were computationally predicted to affect CYP2W1 protein function, in spite of these variants were heterozygotes. Moreover, the allele frequencies in 6 known SNPs including CYP2W1*2 (2008G > A) and CYP2W1*3 (173A > C) were analyzed, which were significantly lower in Chinese Han (2.9% and 0.0%, respectively) and Uygur (5.2% and 0.0%, respectively) individuals, than those reported previously in Caucasians (9.1% and 33.1%, respectively, P < 0.05). These data provide useful information on the pharmacogenetic studies of CYP2W1 among Chinese and other ethnic populations. PMID- 26683390 TI - While my guitar gently weeps: The 2015 presidential address of the AAST. PMID- 26683389 TI - A pilot study of symptom profiles from a polyp vs an eosinophilic-based classification of chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is likely a biologically heterogeneous disease process. Current guidelines propose subclassification using polyp status while others propose using mucosal eosinophilia. We hypothesized that appropriate CRS subclassification would increase homogeneity of baseline symptoms, and identify characteristic symptoms of each subtype. METHODS: A total of 57 CRS patients undergoing surgery prospectively completed a preoperative battery of 73 questions relating to symptoms including the 22-item Sino-Nasal Outcome Test (SNOT-22) and 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) general quality of life (QOL) measures. Eosinophilic cationic protein (ECP) levels were determined from ethmoid, uncinate, and polyp tissue homogenates using enzyme-linked immunosorbent assay (ELISA) and normalized to total protein. Patients were classified as eosinophilic (eCRS) or non-eosinophilic (neCRS) using a 95th percentile threshold established from control tissue from 82 patients without CRS. Separate pairwise comparisons were performed on patient-reported symptoms using polyp and eosinophilic status. RESULTS: Of the 57 patients, 28 had CRS with nasal polyps (CRSwNP); 27 of 57 patients had eCRS (CRSwNP, n = 21; CRS without nasal polyps [CRSsNP], n = 6). CRSwNP patients had increased need to blow nose, frequency of nasal congestion, more severe difficulty breathing through nose, more severe nasal discharge, but less cough (p < 0.05). eCRS patients had more bothersome loss of taste/smell, ear pain, sneezing, severe difficulty breathing through nose, and severe nasal congestion compared to neCRS patients (p < 0.05). CONCLUSION: Subclassifying CRS with symptoms alone is difficult with neither polyp status nor eosinophilia giving a distinctive clinical symptom profile. However, certain symptoms may help otolaryngologists identify CRS subtypes, which may help guide future treatments. Further validation and evaluation of prognosis following treatment is required to evaluate appropriate means of subclassifying CRS. PMID- 26683391 TI - Implementation of an image sharing system significantly reduced repeat computed tomographic imaging in a regional trauma system. AB - BACKGROUND: The practice of repeating computed tomography (re-CT) is common among trauma patients transferred between hospitals incurring additional cost and radiation exposure. This study sought to evaluate the effectiveness of implementing modern cloud-based technology (lifeIMAGE) across a regional trauma system to reduce the incidence of re-CT imaging. METHODS: This is a prospective interventional study to evaluate outcomes after implementation of lifeIMAGE in January 2012. Key outcomes were rates of CT imaging, including the rates and costs of re-CT from January 2009 through December 2012. RESULTS: There were 1,081 trauma patients transferred from participating hospitals during the study period (657 patients before and 425 patients after implementation), with the overall re CT rate of 20.5%. Rates of any CT imaging at referring hospitals decreased (62% vs. 55%, p < 0.05) and also decreased at the accepting regional Level I center (58% vs. 52%, p < 0.05) following system implementation. There were 639 patients (59%) who had CT imaging performed before transfer (404 patients before and 235 patients after implementation). Of these patients, the overall re-CT rate decreased from 38.4% to 28.1% (p = 0.01). Rates of re-CT of the head (21% vs. 11%, p = 0.002), chest (7% vs. 3%, p = 0.05), as well as abdomen and pelvis (12% vs. 5%, p = 0.007) were significantly reduced following system implementation. The cost of repeat imaging per patient was significantly lower following system implementation (mean charges, $1,046 vs. $589; p < 0.001). These results were more pronounced in a subgroup of patients with an Injury Severity Score (ISS) of greater than 14, with a reduction in overall re-CT rate from 51% to 30% (p = 0.03). CONCLUSION: The implementation of modern cloud-based technology across the regional trauma system resulted in significant reductions in re-CT imaging and cost. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV; economic analysis, level IV. PMID- 26683392 TI - The use of an institutional pediatric abdominal trauma protocol improves resource use. AB - BACKGROUND: A novel protocol to standardize the emergency center (EC) management of abdominal trauma in children was developed and implemented at our trauma center. The purpose of this study was to evaluate whether this protocol improved patient safety by decreasing unnecessary computed tomography (CT) radiation and improved quality of care by decreasing EC length of stay (LOS) and laboratory costs. METHODS: We performed a prospective, longitudinal study of children who presented to the EC with a mechanism for abdominal trauma and received an abdominal CT scan from January 2011 to September 2014. Patients were divided into protocol periods: preimplementation (January 2011 to December 2011), Postimplementation 1 (January 2012 to August 2013), and Postimplementation 2 (September 2013 to September 2014). Outcome measures included protocol adherence, rates of clinically positive CT results, the EC LOS, and the cost of laboratory studies. chi and analysis of variance were used for statistical analysis. RESULTS: During the study period, 117 patients in the preimplementation, 148 patients in the Postimplementation 1, and 56 patients in the Postimplementation 2 periods were identified. Protocol adherence improved from 70% to 82% (p = 0.11) from the Postimplementation 1 to Postimplementation 2 periods. The rate of positive CT scan results increased from 23% to 31% to 46% (p = 0.003) from preimplementation to Postimplementation 1 and Postimplementation 2, respectively. When the protocol was followed, the proportion of clinically significant scans was higher than when it was not followed (31% vs. 8%, p = 0.001). The EC LOS was unchanged (median [range], 271 minutes [16-1,039 minutes] vs. 233 minutes [40 1,396 minutes], p = 0.34). The median cost of laboratory studies remained the same from preimplementation to Postimplementation 1 ($166 [$0-$454] vs. $352 [$0 $448], p = 0.29) and decreased after the second protocol revision included an emphasis on laboratory work in Postimplementation 2 ($139 [$33-$426], p = 0.005). CONCLUSION: The use of an institutional abdominal trauma management algorithm is an effective method of improving resource use by decreasing unnecessary CT scan use and laboratory costs. LEVEL OF EVIDENCE: Economic analysis, level IV; therapeutic/care management study, level IV. PMID- 26683393 TI - Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model. AB - BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug that was shown to increase survival in trauma patients, but the mechanisms remain unclear. The purpose of this double-blinded, randomized placebo-controlled study was to determine if TXA with hypotensive resuscitation with Hextend (HEX) or fresh frozen plasma (FFP) reduced blood loss (BL) and improved survival in a model of uncontrolled hemorrhage. METHODS: Instrumented, anesthetized pigs (n = 11 per group) were subjected to 24-mL/kg controlled hemorrhage, followed by transection of the spleen. After 15 minutes of bleeding, TXA (1.43 mg/kg/min) or normal saline (NS) was given over 10 minutes, and then 15-mL/kg HEX or FFP was administered. At 90 minutes, a second infusion of TXA or NS was given. BL, coagulation status, and 5-hour survival were determined. Tissue plasminogen activator (tPA) was added to blood samples collected before and after TXA administration to confirm that the TXA inhibited fibrinolysis. In addition, a comparison of a dose response to tPA-induced fibrinolysis was made between swine and human plasma in vitro. RESULTS: TXA prevented the rise in d-dimers that occurred after spleen injury. However, there was no significant effect of TXA on survival or BL compared with NS with HEX (HEX + NS, 17 +/- 2 mL/kg vs. HEX + TXA, 17 +/- 2 mL/kg) or FFP (FFP + NS, 7 +/- 2 mL/kg vs. FFP + TXA, 12 +/- 3 mL/kg), while FFP significantly reduced BL and increased survival compared with HEX in the NS-treated animals. The tPA-induced fibrinolysis was inhibited in the blood from TXA-treated animals, yet in fibrinolysis sensitivity studies, human plasma was 30 times more sensitive to tPA-induced fibrinolysis than swine plasma. CONCLUSION: TXA did not reduce BL, even though TXA was antifibrinolytic in the pigs. The possibility remains that the pig is highly resistant to fibrinolysis and not a good model to study the effects of antifibrinolytics or that fibrinolysis is not a major factor in bleeding from splenic injury. PMID- 26683394 TI - Can contrast-enhanced ultrasonography improve Zone III REBOA placement for prehospital care? AB - BACKGROUND: Torso hemorrhage is the primary cause of potentially preventable mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been advocated as an adjunct to bridge patients to definitive hemorrhage control. The primary aim of this study was to assess whether contrast enhanced ultrasonography can improve the accuracy of REBOA placement in the infrarenal aorta (Zone III). METHODS: A fluoroscopy-free "enhanced" Zone III REBOA technique was developed using a porcine cadaver model. A "standard" over the-wire Seldinger technique was used, which was enhanced with the addition of a microbubble contrast medium to inflate the balloon, observed with ultrasonography. Following this, attending- and resident-level physicians were randomized into two groups. They were taught either the enhanced with ultrasonography guidance (Group A) or the standard measuring length of catheter insertion (Group B) technique as part of a human cadaver trauma skills course. Outcomes assessed included time (seconds) from insertion to inflation, accuracy, and missed targets. All results were benchmarked against three endovascular experts. RESULTS: There were 20 participants who performed REBOA with Group A (51 [31]) being significantly faster than Group B (90 [63]) (p = 0.003) and more accurate (p = 0.023) with no missed targets. Group B had five missed targets, the most common error being inflation within Zone II. CONCLUSION: For Zone III REBOA, contrast-enhanced ultrasonography technique is faster and more accurate than the standard technique. This may have value in time-critical and austere environments. Clinical studies are now required to evaluate this approach further. PMID- 26683395 TI - RibScore: A novel radiographic score based on fracture pattern that predicts pneumonia, respiratory failure, and tracheostomy. AB - BACKGROUND: There is currently no scoring system for rib fractures that relates detailed anatomic variables to patient outcomes. Our objective was to develop and validate a radiographic rib fracture scoring system based on computed tomographic chest findings. METHODS: We reviewed our trauma registry from September 2012 to April 2014 for all blunt trauma patients with one or more rib fractures visualized on chest computed tomography. We identified the following six candidate radiographic variables and tested their individual associations with pneumonia, respiratory failure, and tracheostomy: (1) six or more rib fractures, (2) bilateral fractures, (3) flail chest, (4) three or more severely (bicortical) displaced fractures, (5) first rib fracture, and (6) at least one fracture in all three anatomic areas (anterior, lateral, and posterior). We developed the "RibScore" by assigning 1 point for each variable, which was validated among the sample using univariate analyses, test performance characteristics, and the receiver operating characteristic area under the curve c statistic. RESULTS: A total of 385 patients with one or more rib fractures were identified; 274 (71.2%) were males, median age was 48 years, and median Injury Severity Score (ISS) was 17. Of these patients, 156 had six or more rib fractures, 120 had bilateral fractures, 46 had flail chest, 32 had three or more severely displaced fractures, 91 had a first rib fracture, and 58 had fractures in all three anatomic areas. Each RibScore component variable was associated with the three pulmonary outcomes by univariate analysis (p < 0.05). The median RibScore was 1 (range, 0-6). The distribution of the RibScore was as follows: score of 0, 41.9%); score of 1, 23.9%; score of 2, 15.4%; score of 3, 9.9%; score of 4, 7.6%; and score of five, 1.3%. RibScore was linearly associated with pneumonia (p < 0.01), acute respiratory failure (p < 0.01), and tracheostomy (p < 0.01). The receiver operating characteristic areas under the curve for the outcomes were 0.71, 0.71, and 0.75, respectively. CONCLUSION: The RibScore predicts adverse pulmonary outcomes and represents a standardized assessment of fracture severity that may be used for communication and prognostication of the severely injured trauma patient. LEVEL OF EVIDENCE: Prognostic study, level III. PMID- 26683396 TI - Pharmacological targeting of chemokine (C-X-C motif) receptor 4 in porcine polytrauma and hemorrhage models. AB - BACKGROUND: Recent evidence suggests that chemokine receptor CXCR4 regulates vascular alpha1-adrenergic receptor function and that the noncognate CXCR4 agonist ubiquitin has therapeutic potential after trauma/hemorrhage. Pharmacologic properties of ubiquitin in large animal trauma models, however, are poorly characterized. Thus, the aims of the present study were to determine the effects of CXCR4 modulation on resuscitation requirements after polytrauma, to assess whether ubiquitin influences survival times after lethal polytrauma hemorrhage, and to characterize its dose-effect profile in porcine models. METHODS: Anesthetized pigs underwent polytrauma (PT, femur fractures/lung contusion) alone (Series 1) or PT/hemorrhage (PT/H) to a mean arterial blood pressure of 30 mmHg with subsequent fluid resuscitation (Series 2 and 3) or 40% blood volume hemorrhage within 15 minutes followed by 2.5% blood volume hemorrhage every 15 minutes without fluid resuscitation (Series 4). In Series 1, ubiquitin (175 and 350 nmol/kg), AMD3100 (CXCR4 antagonist, 350 nmol/kg), or vehicle treatment 60 minutes after PT was performed. In Series 2, ubiquitin (175, 875, and 1,750 nmol/kg) or vehicle treatment 60 minutes after PT/H was performed. In Series 3, ubiquitin (175 and 875 nmol/kg) or vehicle treatment at 60 and 180 minutes after PT/H was performed. In Series 4, ubiquitin (875 nmol/kg) or vehicle treatment 30 minutes after hemorrhage was performed. RESULTS: In Series 1, resuscitation fluid requirements were significantly reduced by 40% with 350 nmol/kg ubiquitin and increased by 25% with AMD3100. In Series 2, median survival time was 190 minutes with vehicle, 260 minutes with 175-nmol/kg ubiquitin, and longer than 420 minutes with 875-nmol/kg and 1,750-nmol/kg ubiquitin (p < 0.05 vs. vehicle). In Series 3, median survival time was 288 minutes with vehicle and 336 minutes and longer than 420 minutes (p < 0.05 vs. vehicle) with 175-nmol/kg and 875-nmol/kg ubiquitin, respectively. In Series 4, median survival time was 147.5 minutes and 150 minutes with vehicle and ubiquitin, respectively (p > 0.05). CONCLUSION: These findings further suggest CXCR4 as a drug target after PT/H. Ubiquitin treatment reduces resuscitation fluid requirements and provides survival benefits after PT/H. The pharmacological effects of ubiquitin treatment occur dose dependently. PMID- 26683397 TI - Multicenter validation of the Quality of Trauma Care Patient-Reported Experience Measure (QTAC-PREM). AB - BACKGROUND: Incorporating patient and family perspectives into injury care quality assessment is a necessary part of comprehensive quality improvement. However, tools to measure patient and family perspectives of injury care are lacking. Therefore, our objective was to assess the psychometric properties of the Quality of Trauma Care Patient-Reported Experience Measure (QTAC-PREM), the first measure developed to assess patient experiences with overall injury care. METHODS: We conducted a prospective multicenter cohort study of adult injury patients recruited from three trauma centers. Patients or surrogates completed an acute care survey measure in the hospital and a post-acute care survey measure after hospital discharge. RESULTS: Four hundred participants (78%) completed the acute care measure, and 207 (59%) completed the post-acute care measure. We identified three subscales on the acute measure and two subscales on the post acute measure. All subscales and items had evidence of construct validity. Four subscales had good internal consistency, and three were independent predictors of participants' overall ratings of injury care quality. The majority of items demonstrated suitable test-retest reliability. Comparison of QTAC-PREM scores with those of an existing patient experience tool, the Hospital version of the Consumer Assessment of Healthcare Providers and Systems (HCAHPS), demonstrated evidence of appropriate divergent and convergent validity. CONCLUSION: This study demonstrates that the QTAC-PREM is feasible to implement at trauma centers and provides evidence of validity and reliability. The tool may be useful to incorporate patient perspectives into trauma care quality measurement and improvement. PMID- 26683398 TI - Needle decompression of tension pneumothorax: Population-based epidemiologic approach to adequate needle length in healthy volunteers in Northeast Germany. AB - BACKGROUND: Tension pneumothorax is one of the leading causes of preventable death in both military and civilian trauma patients. Needle decompression is recommended in trauma guidelines as an emergency procedure to relieve increased intrapleural pressure. The main reason for decompression failure is reported to be insufficient needle length in proportion to the chest wall thickness (CWT). So far, population-based epidemiologic data on CWT are missing. Therefore, it was the aim of this work to investigate the CWT in the second intercostal space, midclavicular line, based on magnetic resonance imaging data of a large population-based sample. The second aim of this study was to explore the potential risk of iatrogenic lesions caused by the proximity of the intended puncture track to the internal mammary artery. METHODS: A total of 2,574 healthy volunteers (mean [SD] age, 53.3 [13.9] years; range, 21-89 years) from the population-based cohort Study of Health in Pomerania (SHIP) were enrolled. CWT and the distance from the intended puncture track to the internal mammary artery were investigated with the chest sequences of a standardized 1.5-T whole-body magnetic resonance imaging. RESULTS: For all 5,148 measured sites in 2,574 volunteers, the mean (SD) CWT was 5.1 (1.4) cm. The mean body mass index was determined to be 27.7 kg/m. The CWT correlated significantly with body weight and body mass index. The internal mammary artery was located medial to the intended puncture site in all participants; the mean (SD) distance was 5.7 (0.7) cm on the right and 5.5 (0.7) cm on the left side. CONCLUSION: Based on the population based epidemiologic data presented in this study, the use of a needle of 7 cm in length is recommended to decompress a tension pneumothorax in the second intercostal space in the midclavicular line, which might successfully decompress more than 90% of the participants in this study. When using this anterior approach at the anatomically correct puncture site, safety margin to the internal mammary artery is sufficient so that the risk of iatrogenic lesion of the internal mammary artery should be minimal. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV. PMID- 26683399 TI - Improvised explosive device-related lower genitourinary trauma in current overseas combat operations. AB - BACKGROUND: The use of improvised explosive devices (IEDs) has had a profound effect on battlefield trauma in the 21st century. Historically, wounds to the genitourinary (GU) structures have been less common than extremity and penetrating abdominal trauma in combat operations. GU injury incidence, severity, and associated injuries secondary to the use of this weapon in Operations Iraqi and Enduring Freedom has not been described. METHODS: Data from the Department of Defense Trauma Registry was reviewed for combat-related GU injuries in Operations Iraqi and Enduring Freedom from 2001 to 2011. All wounded US armed service members are included in this database. Subjects were selected by a query of current procedural terminology and DRG International Classification of Diseases 9th Rev. codes related to traumatic injury of the penis, scrotum, testicles, and urethra. A retrospective chart review was performed for each patient to identify the date of injury, the mechanism of injury, and the associated traumatic wounds. Subjects' follow-up records were reviewed until present time or separation from active duty. RESULTS: A total of 501 soldiers sustained lower GU trauma, with a total of 729 injuries. Of these casualties, 448 (89%) were wounded by IEDs. Dismounted injuries (87%) made up more of the cohort than did vehicular. Specific trauma sites include 149 (20%) penile, 260 (36%) testicular, 284 (39%) scrotal, and 36 (5%) urethral injuries. The 180 limb amputations (36%) and 86 fractures (17%) were the most encountered concomitant skeletal wounds among service members with GU injuries. CONCLUSION: This is the first review of all lower GU trauma sustained by all US armed service members in current overseas combat operations. Combat-related lower GU trauma is primarily caused by IEDs in the spectrum of complex dismounted blast injuries. The mechanism primarily results in multisystem injury, with isolated GU involvement being uncommon. Continued evaluation of long term sequelae, including sexual, urinary, and reproductive dysfunction, is needed. LEVEL OF EVIDENCE: Epidemiologic study, level V. PMID- 26683400 TI - Adenosine, lidocaine, and Mg2+ (ALM): From cardiac surgery to combat casualty care--Teaching old drugs new tricks. AB - New frontline drugs and therapies are urgently required to protect the body from primary and secondary injuries. We review more than 10 years of work on adenosine, lidocaine, and magnesium (ALM) and its possible significance to civilian and military medicine. Adenosine is an endogenous nucleoside involved in nucleotide production, adenosine triphosphate turnover, and restoration of supply and demand imbalances. Lidocaine is a local anesthetic and Class 1B antiarrhythmic, and magnesium is essential for ionic regulation and cellular bioenergetics. Individually, each plays important roles in metabolism, immunomodulation, inflammation, and coagulation. The original idea to combine all three was as a "polarizing" cardioplegia, an idea borrowed from natural hibernators. Two recent prospective, randomized human trials have demonstrated its safety and superiority in myocardial protection over high-potassium "depolarizing" solutions. The next idea came from witnessing how the human heart spontaneously reanimated after complex operations with little inotropic support. At high doses, ALM arrests the heart, and at lower doses, it resuscitates the heart. In rat and pig models, we have shown that ALM intravenous bolus and infusion "drip" protects against acute regional myocardial ischemia, lethal arrhythmias, cardiac arrest, compressible and noncompressible blood loss and shock, endotoxemia, and sepsis. Individually, adenosine, lidocaine, or magnesium fails to protect. Protection is afforded in part by reducing inflammation, correcting coagulopathy, and lowering energy demand. We propose a unifying hypothesis involving improved central, cardiovascular and endothelium coupling to maintain sufficient tissue oxygenation and reduce primary and secondary "hit" complications. As with any new drug innovation, translation into humans is challenging. PMID- 26683401 TI - A global agenda for electronic injury surveillance: Consensus statement from the Trauma Association of Canada, the Trauma Society of South Africa, and the Panamerican Trauma Society. PMID- 26683404 TI - HbA1c measurement and relationship to incident stroke. AB - AIMS: To determine the proportion of people with diabetes who have HbA1c measured, what proportion achieve an HbA1c level of < 58 mmol/mol (7.5%), the frequency of testing and if there was any change in HbA1c level in the year before and the year after an incident stroke. METHODS: This study used the Secure Anonymised Information Linkage (SAIL) databank, which stores hospital data for the whole of Wales and ~ 65% of Welsh general practice records, to identify cases of stroke in patients with diabetes between 2000 and 2010. These were matched against patients with diabetes but without stroke disease. We assessed the frequency of HbA1c testing and change in HbA1c in the first year after stroke. Estimation was made of the proportion of patients achieving an HbA1c measurement <= 58 mmol/mol (7.5%). RESULTS: There were 1741 patients with diabetes and stroke. Of these, 1173 (67.4%) had their HbA1c checked before their stroke and 1137 (65.3%) after their stroke. In the control group of 16 838 patients with diabetes but no stroke, 8413 (49.9%) and 9288 (55.1%) had their HbA1c checked before and after the case-matched stroke date, respectively. In patients with diabetes and stroke, HbA1c fell from 61-56 mmol/mol (7.7-7.3%) after their stroke (P < 0.001). Before the study, 55.0% of patients with stroke had an HbA1c >= 58 mmol/mol compared with 65.2% of control patients, these figures were 62.5% and 65.3% after the stroke. CONCLUSIONS: The frequency of diabetes testing was higher in patients who had experienced a stroke before and after their incident stroke compared with control patients but did not increase after their stroke. Glucose control improved significantly in the year after a stroke. PMID- 26683406 TI - Active Surveillance for Ductal Carcinoma in Situ: Shining Light Into the Modeling Abyss. PMID- 26683405 TI - Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis. AB - BACKGROUND: Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS. METHODS: Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed. RESULTS: Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis. CONCLUSION: AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging. PMID- 26683408 TI - A doctor's duty of disclosure and the decline of 'The Bolam Test': A dramatic change in the law on patient consent. PMID- 26683407 TI - Whole-Body and Microenvironmental Localization of Radium-223 in Naive and Mouse Models of Prostate Cancer Metastasis. AB - BACKGROUND: Bone-metastatic, castration-resistant prostate cancer (bmCRPC) represents a lethal stage of the most common noncutaneous cancer in men. The recent introduction of Radium-223 dichloride, a bone-seeking alpha particle (alpha)-emitting radiopharmaceutical, demonstrates statistically significant survival benefit and palliative effect for bmCRPC patients. Clinical results have established safety and efficacy, yet questions remain regarding pharmacodynamics and dosing for optimized patient benefit. METHODS: We elucidated the biodistribution of (223)Ra as well as interaction with the bone and tumor compartments in skeletally mature mice (C57Bl/6 and CD-1, n = 3-6) and metastasis models (LNCaP and PC3, n = 4). Differences in uptake were evaluated by uCT and histological investigation. Novel techniques were leveraged on whole-mount undecalcified cryosections to determine microdistribution of Radium-223. All statistical tests were two-sided. RESULTS: (223)Ra uptake in the bones (>30% injected activity per gram) at 24 hours was also accompanied by non-negligible remnant activity in the kidney (2.33% +/- 0.36%), intestines (5.73% +/- 2.04%), and spleen (10.5% +/- 5.9%) Skeletal accumulation across strains did not correspond with bone volume or surface area but instead to local blood vessel density (P = .04). Microdistribution analysis by autoradiography and alpha camera revealed targeting of the ossifying surfaces adjacent to the epiphyseal growth plate. In models of PCa metastasis, radioactivity does not localize directly within tumors but instead at the apposite bone surface. Osteoblastic and lytic lesions display similar intensity, which is comparable with uptake at sites of normal bone remodeling. CONCLUSIONS: Profiling the macro- and microdistribution of (223)Ra in healthy and diseased models has important implications to guide precision application of this emerging alpha-therapy approach for bmCRPC and other bone metastastic diseases. PMID- 26683409 TI - Occlusal Pressure Analysis of Complete Dentures after Microwave Disinfection: A Clinical Study. AB - PURPOSE: This clinical study evaluated the effect of microwave disinfection protocols on the occlusal pressure pattern of dentures. MATERIALS AND METHODS: Dentures were constructed for 40 patients and evaluated as follows (n = 20). Group 1: Patients had the maxillary dentures submitted to microwave disinfection, once a week, for 4 weeks. Group 2: Patients had the maxillary dentures submitted to microwave disinfection, three times a week, for 4 weeks. Occlusal contacts were recorded on five occasions: 30 days after denture insertion and before first disinfection (baseline or control group); 1 week after disinfection; 2 weeks after disinfection; 3 weeks after disinfection; 4 weeks after disinfection. Occlusal contacts were analyzed by T-Scan III. Intergroup analysis was performed using the Mann-Whitney test and intragroup analysis using the Friedman test with significance of 5%. RESULTS: The results showed no significant difference between groups during the periods. The data on parameters loss of denture adaptation or complaints showed that patients used their dentures regularly for eating and expressed comfort and satisfaction in all experimental periods. The evaluation of functional occlusion revealed that the distribution of the occlusal contacts remained unaltered after disinfection. CONCLUSION: Microwave disinfection protocols as studied in this report did not influence occlusal contacts of the complete dentures. PMID- 26683410 TI - Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates. AB - In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed. PMID- 26683411 TI - Regenerative potential of immature permanent non-vital teeth following different dentin surface treatments. AB - This study evaluates the regenerative potential of immature permanent non-vital teeth following different dentin surface treatments in dogs. Periapical lesions and necrotic pulps were induced in 288 roots of 144 teeth in twelve dogs. Teeth were randomly divided into 3 equal groups according to the evaluation period. Each group was subdivided into 8 subgroups according to the treatment modalities including; blood clot, blood clot and collagen, blood clot and Ethylenediaminetetraacetic acid (EDTA), blood clot, collagen and EDTA, blood clot and Mixture Tetracycline Citric Acid and Detergent (MTAD), blood clot, collagen and MTAD, positive control and negative control. Apart from control subgroups, all infected root canals were cleaned with sodium hypochlorite solution and triple antibiotics paste before different treatment protocols. After different treatments, the root length, thickness and apical diameter were evaluated by radiographic examination. Histopathological examination was carried out to evaluate the inflammation, bone/root resorption, tissue in-growth in pulp space, new hard tissue formation and apical closure. Using EDTA solution as a surface modifier showed significantly higher levels of tissue in-growth in the pulp space after 6 weeks and 3 months. Addition of collagen as a scaffold caused significantly more bone/root resorption than the other subgroups while EDTA caused significantly lower inflammatory cell counts only after 2 weeks. Final rinse with 17% EDTA solution before blood clot induction has positive impact on tissue interaction along dentinal walls without modification of the cell type. Moreover, the use of collagen as a scaffold material and MTAD as a surface modifier did not improve the quality of the regenerative process. PMID- 26683412 TI - Ultrasonic backscatter from cancellous bone: the apparent backscatter transfer function. AB - Ultrasonic backscatter techniques are being developed to detect changes in cancellous bone caused by osteoporosis. Many techniques are based on measurements of the apparent backscatter transfer function (ABTF), which represents the backscattered power from bone corrected for the frequency response of the measurement system. The ABTF is determined from a portion of the backscatter signal selected by an analysis gate of width tauw delayed by an amount taud from the start of the signal. The goal of this study was to characterize the ABTF for a wide range of gate delays (1 MUs <= taud <= 6 MUs) and gate widths (1 MUs <= tauw <= 6 MUs). Measurements were performed on 29 specimens of human cancellous bone in the frequency range 1.5 to 6.0 MHz using a broadband 5-MHz transducer. The ABTF was found to be an approximately linear function of frequency for most choices of taud and tauw. Changes in taud and tauw caused the frequency-averaged ABTF [quantified by apparent integrated backscatter (AIB)] and the frequency dependence of the ABTF [quantified by frequency slope of apparent backscatter (FSAB)] to change by as much as 24.6 dB and 6.7 dB/MHz, respectively. taud strongly influenced the measured values of AIB and FSAB and the correlation of AIB with bone density (-0.95 <= R <= +0.68). The correlation of FSAB with bone density was influenced less strongly by taud (-0.97 <= R <= -0.87). tauw had a weaker influence than taud on the measured values of AIB and FSAB and the correlation of these parameters with bone density. PMID- 26683413 TI - Dynamics and regulation of glycolysis-tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis. AB - Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis-tricarboxylic acid (glycolysis-TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down-regulated in prepupae and then recovered in some degree in pupae, and all TCA-related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up-regulate glycolysis but down-regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down-regulated by starvation, indicating that non-feeding during metamorphosis may be a regulator of glycolysis-TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis. PMID- 26683415 TI - Maryland Alcohol Sales Tax and Sexually Transmitted Infections: A Natural Experiment. AB - INTRODUCTION: Sexually transmitted infections are common causes of morbidity and mortality, including infertility and certain types of cancer. Alcohol tax increases may decrease sexually transmitted infection rates overall and differentially across population subgroups by decreasing alcohol consumption in general and prior to sex, thus decreasing sexual risk taking and sexually transmitted infection acquisition. This study investigated the effects of a Maryland increase in alcohol beverage sales tax on statewide gonorrhea and chlamydia rates overall and within age, gender, and race/ethnicity subpopulations. METHODS: This study used an interrupted time series design, including multiple cross-state comparisons, to examine the effects of the 2011 alcohol tax increase in Maryland on chlamydia and gonorrhea cases reported to the U.S. National Notifiable Disease Surveillance System for January 2003 to December 2012 (N=120 repeated monthly observations, analyzed in 2015). Effects were assessed with Box-Jenkins autoregressive moving average models with structural parameters. RESULTS: After the alcohol-specific sales tax increase, gonorrhea rates decreased 24% (95% CI=11%, 37%), resulting in 1,600 fewer statewide gonorrhea cases annually. Cohen's d indicated a substantial effect of the tax increase on gonorrhea rates (range across control group models, -1.25 to -1.42). The study did not find evidence of an effect on chlamydia or differential effects across age, race/ethnicity, or gender subgroups. CONCLUSIONS: Results strengthen the evidence from prior studies of alcohol taxes influencing gonorrhea rates and extend health prevention effects from alcohol excise to sales taxes. Alcohol tax increases may be an efficient strategy for reducing sexually transmitted infections. PMID- 26683416 TI - Injectable collagenase Clostridium histolyticum as a nonsurgical treatment for Dupuytren's disease. AB - OBJECTIVE: Nonsurgical treatment of Dupuytren's disease using collagenase Clostridium histolyticum (CCH). INDICATIONS: Metacarpophalangeal (MP) joint (20 100 degrees ) and proximal interphalangeal (PIP) joint (20-80 degrees ) contractures. CONTRAINDICATIONS: Pregnancy, previous hypersensitivity to collagenase or excipients, anticoagulant use within 7 days prior to treatment. INJECTION TECHNIQUE: CCH injected directly into the Dupuytren's cord weakening the contracted cord. After injection, the patient returns the following day to allow CCH to lyse the collagen within the cord. An extension force is then applied to the involved finger to disrupt the weakened cord. POSTMANIPULATION MANAGEMENT: Use of extension splint at night, movement instructions during the day. RESULTS: A total of 120 patients (107 men; 13 women; mean age 62 years, range 30-84 years) were treated. In 49% the little finger, in 44% the ring finger, in 4% the middle finger, and in 3% the index finger was treated. Full release was achieved in 71%, partial release in 26%, and no change in 3% of patients. The median pretreatment contracture for the MP joint was 37 degrees (range 25-100 degrees ) and PIP joint 51 degrees (range 30-97 degrees ). At 12 months, the mean contracture for the MP joint was 9 degrees (range 0-25 degrees ) and for the PIP joint 21 degrees (range 10-36 degrees ). Adverse events observed in 96% of patients for 3 months . No tendon ruptures, anaphylactic reactions, or nerve or ligament injuries observed. PMID- 26683419 TI - Image-guided surgery. PMID- 26683420 TI - Atopy: a risk factor of refractory mycoplasma pneumoniae pneumonia? AB - OBJECTIVE: To investigate the relationship of pathogen DNA copies with clinic and laboratory features among children with Mycoplasma pneumoniae (MP) pneumonia. METHODS: A total of 95 enrolled children with MP pneumonia were assigned into the high-MP-load group (>106 /mL) and the low-MP-load group (<=106 /mL) according to MP-DNA copies in bronchoalveolar lavage fluid (BALF). Clinical characteristics and any allergy history were collected. Aeroallergens and food allergens were detected with a skin test. Serum IgE and eosinophil cationic protein (ECP) were assessed using enzyme immunoassay. BALF levels of IL-4, IFN-gamma, IL-8 and TNF alpha were assessed by ELISA. RESULTS: Compared with the low-MP-load group, 72.7% in the high-MP-load group developed refractory MP pneumonia who failed to respond to at least 1-week treatment with macrolides (72.7% vs 41.9%, P = 0.005). More children in the high-load group than those in the low-load group presented with extrapulmonary manifestations, lung consolidation, pleural effusion and atopic conditions including any allergy history, positive findings of aeroallergen test and increased serum IgE and ECP (P < 0.05). A significant higher BALF IL-4 level was seen in the high-load group versus the low-load group (23.00 +/- 11.24 vs 14.68 +/- 7.12; pg/mL; P < 0.01). There were no significant differences in BALF levels of IFN-gamma, IL-8 and TNF-alpha between the two groups (P > 0.05). CONCLUSION: Atopy may be a risk factor for the presence and severity of refractory MP pneumonia due to the high pathogen load in airway. PMID- 26683421 TI - Fingolimod targeting protein phosphatase 2A differently affects IL-33 induced IL 2 and IFN-gamma production in CD8(+) lymphocytes. AB - Multiple sclerosis patients are treated with fingolimod (FTY720), a prodrug that acts as an immune modulator. FTY720 is first phosphorylated to FTY720-P and then internalizes sphingosine-1-phosphate receptors, preventing lymphocyte sequestration. IL-33 is released from necrotic endothelial cells and contributes to MS severity by coactivating T cells. Herein we analyzed the influence of FTY720, FTY720-P, and S1P on IL-33 induced formation of IL-2 and IFN-gamma, by using IL-33 receptor overexpressing EL4 cells, primary CD8(+) T cells, and splenocytes. EL4-ST2 cells released IL-2 after IL-33 stimulation that was inhibited dose-dependently by FTY720-P but not FTY720. In this system, S1P increased IL-2, and accordingly, inhibition of S1P producing sphingosine kinases diminished IL-2 release. In primary CD8(+) T cells and splenocytes IL-33/IL-12 stimulation induced IFN-gamma, which was prevented by FTY720 but not FTY720-P, independently from intracellular phosphorylation. The inhibition of IFN-gamma by nonphosphorylated FTY720 was mediated via the SET/protein phosphatase 2A (PP2A) pathway, since a SET peptide antagonist also prevented IFN-gamma formation and the inhibition of IFN-gamma by FTY720 was reversible by a PP2A inhibitor. While our findings directly improve the understanding of FTY720 therapy in MS, they could also contribute to side effects of FTY720 treatment, like progressive multifocal leukoencephalopathy, caused by an insufficient immune response to a viral infection. PMID- 26683422 TI - Self-Perceived Pre-Motor Symptoms Load in Patients with Parkinson's Disease: A Retrospective Study. AB - BACKGROUND: Parkinson's disease is characterized by motor and non-motor clinical features. The latter may present as pre-motor symptoms several years before the motor onset. OBJECTIVE: To analyze the association between pre-motor symptoms load and its lead-time in relation to the motor onset and time to diagnosis. METHODS: A cross-sectional study was carried including subjects with Parkinson's disease from five different movement disorders clinics in Mexico. A structured questionnaire was applied to assess the presence of six self-perceived pre-motor symptoms (hyposmia, depression, anxiety, constipation, pain and sleep disorders). RESULTS: Overall frequency of pre-motor symptoms was 76.2% . Among the most prevalent symptoms were depression (38%), sleep disorders (37%) and anxiety (36.6%). The lead time to motor onset was greater for constipation (9.2 +/- 17.89 years) and pain (8.66 +/- 13.36 years). Patients with more than two pre-motor symptoms had a later age at motor onset when compared to patients without pre motor symptoms (52.04 +/- 13.11 vs 56.55 +/- 12.97 years, p = 0.037). Late onset patients had a higher frequency of pre-motor symptoms (79% vs 65% in early onset, p = 0.002) and a higher load (1.75 +/- 1.37 vs 1.44 +/- 1.38, p = 0.033) in comparison to those with early onset. Female subjects reported a higher number of pre-motor symptoms (1.91 +/- 1.43 versus 1.48 +/- 1.29, p <= 0.001). PIGD patients reported a greater frequency of pain (8%) compared to tremor (1%, p = 0.0064) and bradykinetic-rigid (0.61%, p = 0.0061). Anxiety lead-time was greater in tremor-dominant (10.83 +/- 15.77 years) compared to bradykinetic-rigid patients (3.48 +/- 12.56, p = 0.014). CONCLUSIONS: Pre-motor symptoms load is associated to a later motor onset of PD. Pre-motor symptoms are more frequent in subjects with late onset Parkinson's disease. Female subjects report a higher number of pre-motor symptoms, depression and anxiety being the most common. PMID- 26683423 TI - Test Accuracy of Informant-Based Cognitive Screening Tests for Diagnosis of Dementia and Multidomain Cognitive Impairment in Stroke. AB - BACKGROUND AND PURPOSE: Poststroke cognitive assessment can be performed using standardized questionnaires designed for family or care givers. We sought to describe the test accuracy of such informant-based assessments for diagnosis of dementia/multidomain cognitive impairment in stroke. METHODS: We performed a systematic review using a sensitive search strategy across multidisciplinary electronic databases. We created summary test accuracy metrics and described reporting and quality using STARDdem and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, respectively. RESULTS: From 1432 titles, we included 11 studies. Ten papers used the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Four studies described IQCODE for diagnosis of poststroke dementia (n=1197); summary sensitivity: 0.81 (95% confidence interval, 0.60-0.93); summary specificty: 0.83 (95% confidence interval, 0.64-0.93). Five studies described IQCODE as tool for predicting future dementia (n=837); summary sensitivity: 0.60 (95% confidence interval, 0.32-0.83); summary specificity: 0.97 (95% confidence interval, 0.70-1.00). All papers had issues with at least 1 aspect of study reporting or quality. CONCLUSIONS: There is a limited literature on informant cognitive assessments in stroke. IQCODE as a diagnostic tool has test properties similar to other screening tools, IQCODE as a prognostic tool is specific but insensitive. We found no papers describing test accuracy of informant tests for diagnosis of prestroke cognitive decline, few papers on poststroke dementia and all included papers had issues with potential bias. PMID- 26683424 TI - Letter by Neugebauer and Juttler Regarding Article, "Poor Collateral Circulation Assessed by Multiphase Computed Tomographic Angiography Predicts Malignant Middle Cerebral Artery Evolution After Reperfusion Therapies". PMID- 26683425 TI - Response to Letter Regarding Article,"Poor Collateral Circulation Assessed by Multiphase Computed Tomographic Angiography Predicts Malignant Middle Cerebral Artery Evolution After Reperfusion Therapies". PMID- 26683426 TI - Early prediction of maxillary canine impaction. AB - OBJECTIVES: The aim of this study was to establish prediction criteria for maxillary canine impaction in young patients, based on angular and linear measurements on panoramic radiographs. METHODS: From 828 records having at least 2 panoramic radiographs, both taken between the ages of 7 and 14 years, with a minimum 1-year and maximum 3-year interval (T1 and T2), a training data set consisting of 30 subjects with unilateral canine impaction (12 males and 18 females) was selected. The patients' mean age was 10.1 years [standard deviation (SD) 1.3 years] at T1 and 11.9 years (SD 1.1 years) at T2. The training data set also consisted of 30 maxillary canines from the contralateral sides and an additional 60 normal erupted canines from 30 subjects. Those 30 subjects of a test data set were selected based on displaying bilateral maxillary canine eruption at T2 and being matched for gender and age with the subjects of the training data set [12 males and 18 females; mean age at T1, 10.1 years (SD 1.3 years) and at T2, 11.1 years (SD 1.2 years)]. Angular and linear measurements were performed separately by two observers on the total study sample at T1. Linear measurements were expressed as a multiplication of the maxillary central incisor width at the non-impacted side. RESULTS: Significant differences for linear and angular measurements and radiographic factors were found between the maxillary impacted canine and erupted maxillary canine. The three best discriminating parameters were canine to first premolar angle, canine cusp to midline distance and canine cusp to maxillary plane distance. These three parameters were combined in a multiple logistic regression model to calculate the probability of impaction, yielding a high area under the curve (AUC) equal to 0.97 (95% confidence interval: 0.94-0.99), with 90% sensitivity and 94% specificity. CONCLUSIONS: Prediction of maxillary canine impaction from a combination of parameters relating to angles and distances measured in panoramic radiographs is weak. However, the final prediction model, based on canine-first premolar angle, canine cusp tip to midline distance and canine cusp tip to maxillary occlusal plane distance, might be useful to discriminate canine impaction for early intervention or regular follow-up. PMID- 26683443 TI - Time-course proteome analysis of developing extrafloral nectaries of Ricinus communis. AB - Floral and extrafloral nectaries are unique organs that secrete energy rich chemical components, but their contribution for nectar production is largely unknown. Here, we present the first comparative proteome dataset of four developmental stages of the extrafloral nectaries from castor plant (Ricinus communis), an important biofuel crop. Respectively, from stage I-IV, we identified 626, 613, 449 and 356 proteins, respectively, summing up 882 nonredundant proteins. Surprisingly, we identified two isoforms of the potent toxin ricin, indicating that ricin expression is not limited to seeds, but it may serve a general defense purpose for the castor plant. To date, this is the most complete dataset of proteins either from floral or extrafloral nectaries, thus contributing to lay the foundations for investigations on their ecological and evolutionary importance. PMID- 26683445 TI - 'I don't consider a cup performance; I consider it a test': masculinity and the medicalisation of infertility. AB - Researchers have deemed medicalisation a 'gendered' theory, yet the incorporation of men and masculinity in medicalisation literature is sparse. Recently, however, medicalisation scholarship has begun studying men. This burgeoning literature heavily emphasises sexuality and is beginning to focus on medicalised masculinities in which traits associated with masculinity are deemed a health risk. Such research has demonstrated how masculinities shape men's lived experiences of health, but how does health itself shape masculinity? I explore this question using the case of infertility. Through thirty in-depth interviews, I find that men use medicine as a way to achieve rather than diminish their sense of masculinity in the feminised context of reproduction. By perpetuating the stereotype that infertility is a woman's problem, the medical establishment has caused men to not necessarily see themselves as infertile. Additionally, even if men do claim the infertility status, they do not perceive it as negative. The legitimating effects of medicalisation objectify the ailment and separate its connection with sexuality. In centring men's voices, the study not only reveals men as active players in the reproductive process, but also incorporates them into understandings of medicalisation. PMID- 26683453 TI - Daily Reports of Positive and Negative Affect and Alcohol and Marijuana Use Among College Student and Nonstudent Young Adults. AB - BACKGROUND: Daily affect and substance use covary among college students, but little is known about these associations among young adults not in college. OBJECTIVES: The current pilot study examines associations between positive and negative affect and alcohol and marijuana use, with a focus on differences between college student and nonstudent young adults. METHODS: High school seniors completed a baseline survey during the spring of 2012 and were then randomly selected to participate in an intensive measurement follow-up. Participants in the follow-up (N = 72, 40.3% men, 77.8% White, 66.7% full-time college students) completed up to 14 consecutive web-based daily surveys during the fall after high school completion. Multilevel models in which days (Level 1) were nested in persons (Level 2) were estimated. RESULTS: Weekend days were associated with increased alcohol use among all young adults, increased marijuana use among college students, and decreased marijuana use among nonstudents. For young adults not in college, greater daily positive affect was associated with increased likelihood of binge drinking, consuming a greater number of drinks, and lower odds of marijuana use; greater daily negative affect was associated with lower odds of alcohol use and lower odds of binge drinking for non-students. For college students, greater daily negative affect was associated with lower odds of marijuana use. CONCLUSIONS/IMPORTANCE: Daily affect and alcohol and marijuana use covary among young adults, though these associations differ between students and non-students. Results highlight the need to examine predictors of alcohol and marijuana use among young adults who do not attend college. PMID- 26683455 TI - Ebola and Other Highly Contagious Diseases: Strategies by the Society of Interventional Radiology for Interventional Radiology. PMID- 26683444 TI - Traumatically injured astrocytes release a proteomic signature modulated by STAT3 dependent cell survival. AB - Molecular markers associated with CNS injury are of diagnostic interest. Mechanical trauma generates cellular deformation associated with membrane permeability with unknown molecular consequences. We used an in vitro model of stretch-injury and proteomic analyses to determine protein changes in murine astrocytes and their surrounding fluids. Abrupt pressure-pulse stretching resulted in the rapid release of 59 astrocytic proteins with profiles reflecting cell injury and cell death, i.e., mechanoporation and cell lysis. This acute trauma-release proteome was overrepresented with metabolic proteins compared with the uninjured cellular proteome, bearing relevance for post-traumatic metabolic depression. Astrocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3-CKO) resulted in reduced stretch-injury tolerance, elevated necrosis and increased protein release. Consistent with more lysed cells, more protein complexes, nuclear and transport proteins were released from STAT3-CKO versus nontransgenic astrocytes. STAT3-CKO astrocytes had reduced basal expression of GFAP, lactate dehydrogenase B (LDHB), aldolase C (ALDOC), and astrocytic phosphoprotein 15 (PEA15), and elevated levels of tropomyosin (TPM4) and alpha actinin 4 (ACTN4). Stretching caused STAT3-dependent cellular depletion of PEA15 and GFAP, and its filament disassembly in subpopulations of injured astrocytes. PEA15 and ALDOC signals were low in injured astrocytes acutely after mouse spinal cord crush injury and were robustly expressed in reactive astrocytes 1 day postinjury. In contrast, alpha crystallin (CRYAB) was present in acutely injured astrocytes, and absent from uninjured and reactive astrocytes, demonstrating novel marker differences among postinjury astrocytes. These findings reveal a proteomic signature of traumatically-injured astrocytes reflecting STAT3-dependent cellular survival with potential diagnostic value. PMID- 26683457 TI - Pre-concentration of trace amount of bisphenol A in water samples by palm leaf ash and determination with high-performance liquid chromatography. AB - Palm leaf ash was characterized and used as low-cost adsorbent for solid-phase extraction and preconcentration of bisphenol A (BPA) in real water samples. Analysis of BPA was carried out using HPLC involving Eurospher 100-5-C18 (25 cm * 4.5 mm, particle size 5 MUm) column and water-acetonitrile (40:60, v/v) as mobile phase. The adsorption was achieved quantitatively at a pH of 6 with elution by 3 mL acetonitrile. The limits of detection and enrichment factor were 0.02 MUg L( 1) and 333, respectively. Under optimum conditions the relative standard deviation (RSD) was 2% (n = 10). Comparison of qualification criteria of presented preconcentration procedure with other research indicated that palm leaf ash adsorbent was better than many of the adsorbents in terms of cost and reusability. Also, the limit of detection, precision and enrichment factor were comparable and even better than the previously reported methods. Finally, the efficiency of method was computed by determination of trace amounts of BPA in sea, river, mineral and tap waters with recoveries of 93.3-105.5% and RSDs of 0.61-3.12%.. Briefly, the developed solid-phase extraction and Preparative layer chromatography (PLC) methods may be used for bisphenol A monitoring in any environmental water sample. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26683456 TI - Cryoablation of Osteoid Osteoma in the Pediatric and Adolescent Population. AB - PURPOSE: To evaluate the technical feasibility and clinical efficacy of osteoid osteoma (OO) cryoablation in a large, pediatric/adolescent cohort. MATERIALS AND METHODS: An electronic medical record and imaging archive review was performed to identify all cryoablations performed for OOs between 2011 and 2015 at a single tertiary care pediatric hospital. The subsequent analysis included 29 patients with suspected OOs treated by cryoablation (age range, 3-18 y; mean age, 11.3 y; 17 boys; 12 girls). Conventional CT guidance was used in 22 procedures; cone-beam CT guidance was used in 7 procedures. Follow-up data were obtained via a standardized telephone questionnaire (23/29 patients; 79.3%) and clinical notes (5/29 patients; 17.2%). One patient was lost to follow-up. RESULTS: Technical success was achieved in 100% of patients (29/29). Immediate clinical success (cessation of pain and nonsteroidal antiinflammatory drug [NSAID] use within 1 mo after the procedure) was achieved in 27/28 patients (96.4%). Short-term clinical success (cessation of pain and NSAID use for > 3 mo after the procedure) was achieved in 24/25 patients (96%). Long-term clinical success (cessation of pain and NSAID use for > 12 mo after the procedure) was achieved in 19/21 patients (90.5%). Median pain scale score before the procedure was 10 (range, 5-10); median pain scale score after the procedure was 0 (range, 0-8; P < .0001). There were 6 minor complications (21%) and no major complications. CONCLUSION: Image guided cryoablation is a technically feasible, clinically efficacious therapeutic option for children and adolescents with symptomatic OO. PMID- 26683458 TI - Genetic Mapping of Novel Loci Affecting Canine Blood Phenotypes. AB - Since the publication of the dog genome and the construction of high-quality genome-wide SNP arrays, thousands of dogs have been genotyped for disease studies. For many of these dogs, additional clinical phenotypes are available, such as hematological and clinical chemistry results collected during routine veterinary care. Little is known about the genetic basis of variation in blood phenotypes, but this variation may play an important role in the etiology and progression of many diseases. From a cohort of dogs that had been previously genotyped on a semi-custom Illumina CanineHD array for various genome-wide association studies (GWAS) at Cornell University Hospital for Animals, we chose 353 clinically healthy, adult dogs for our analysis of clinical pathologic test results (14 hematological tests and 25 clinical chemistry tests). After correcting for age, body weight and sex, genetic associations were identified for amylase, segmented neutrophils, urea nitrogen, glucose, and mean corpuscular hemoglobin. Additionally, a strong genetic association (P = 8.1*10-13) was evident between a region of canine chromosome 13 (CFA13) and alanine aminotransferase (ALT), explaining 23% of the variation in ALT levels. This region of CFA13 encompasses the GPT gene that encodes the transferase. Dogs homozygous for the derived allele exhibit lower ALT activity, making increased ALT activity a less useful marker of hepatic injury in these individuals. Overall, these associations provide a roadmap for identifying causal variants that could improve interpretation of clinical blood tests and understanding of genetic risk factors associated with diseases such as canine diabetes and anemia, and demonstrate the utility of holistic phenotyping of dogs genotyped for disease mapping studies. PMID- 26683459 TI - BMA calls for chief inspector of general practice to resign. PMID- 26683460 TI - Seasonal Synchronization of Diapause Phases in Aedes albopictus (Diptera: Culicidae). AB - In temperate areas, population dynamics of the invasive Asian tiger mosquito Aedes albopictus are strongly affected by winter. The work we present here analyzes the adaptive synchronization of the diapause process in the wintry generation of A. albopictus, where the egg stage is exposed to adverse winter conditions. The seasonal pattern of egg laying activity of a French Mediterranean population of the Asian tiger mosquito was monitored weekly for 2 years with ovitraps. The field diapause incidence and the critical photoperiod (CPP, i.e. the maternal day length inducing diapause in 50% of the eggs), were determined by hatching experiments on the collected eggs. The period of diapause termination was estimated by a field survey of the first hatchings for both years. The CPP is equal to 13.5 hours of light and occurs in the field on the 25th of August. Thus, it is on September 11th, 17 days after the CPP, that 50% of the eggs are in a prediapause stage in the field. The egg diapause rate increases rapidly during September, whereas the mean number of eggs laid decreases sharply after mid September. Surprisingly, after having reached a peak of 95% at the end of September, from mid-October the diapause incidence declined and stayed below 50%. Indeed, both years the diapause initiates before the rapid decrease of the environmental temperature. This leaves a sufficient period of time to the complete development of one generation of A. albopictus with effective induction of diapause in the laid eggs. The very first larvae hatched were sampled both years in the first half of March. With 20 to 26 weeks in the egg stage and about 7 weeks in the larval stages, the first annual generation spends a long time in immature stages. On a practical point of view, this long development time represents a wide window for eggs and larvae control in early spring. PMID- 26683462 TI - Aquatic flower-inspired cell culture platform with simplified medium exchange process for facilitating cell-surface interaction studies. AB - Establishing fundamentals for regulating cell behavior with engineered physical environments, such as topography and stiffness, requires a large number of cell culture experiments. However, cell culture experiments in cell-surface interaction studies are generally labor-intensive and time-consuming due to many experimental tasks, such as multiple fabrication processes in sample preparation and repetitive medium exchange in cell culture. In this work, a novel aquatic flower-inspired cell culture platform (AFIP) is presented. AFIP aims to facilitate the experiments on the cell-surface interaction studies, especially the medium exchange process. AFIP was devised to capture and dispense cell culture medium based on interactions between an elastic polymer substrate and a liquid medium. Thus, the medium exchange can be performed easily and without the need of other instruments, such as a vacuum suction and pipette. An appropriate design window of AFIP, based on scaling analysis, was identified to provide a criterion for achieving stability in medium exchange as well as various surface characteristics of the petal substrates. The developed AFIP, with physically engineered petal substrates, was also verified to exchange medium reliably and repeatedly. A closed structure capturing the medium was sustained stably during cell culture experiments. NIH3T3 proliferation results also demonstrated that AFIP can be applied to the cell-surface interaction studies as an alternative to the conventional method. PMID- 26683461 TI - The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex. AB - BRUCE is implicated in the regulation of DNA double-strand break response to preserve genome stability. It acts as a scaffold to tether USP8 and BRIT1, together they form a nuclear BRUCE-USP8-BRIT1 complex, where BRUCE holds K63 ubiquitinated BRIT1 from access to DSB in unstressed cells. Following DSB induction, BRUCE promotes USP8 mediated deubiquitination of BRIT1, a prerequisite for BRIT1 to be released from the complex and recruited to DSB by binding to gamma-H2AX. BRUCE contains UBC and BIR domains, but neither is required for the scaffolding function of BRUCE mentioned above. Therefore, it remains to be determined whether they are required for BRUCE in DSB response. Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex. Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE-USP8-BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB. This leads to impaired chromatin relaxation, decreased accumulation of MDC1, NBS1, pATM and RAD51 at DSB, and compromised homologous recombination repair of DNA DSB. These results demonstrate that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break. These data support a crucial role for BRUCE UBC activity in the early stage of DSB response. PMID- 26683464 TI - IMAGE FUSION OF RECONSTRUCTED DIGITAL TOMOSYNTHESIS VOLUMES FROM A FRONTAL AND A LATERAL ACQUISITION. AB - Digital tomosynthesis (DTS) has been used in chest imaging as a low radiation dose alternative to computed tomography (CT). Traditional DTS shows limitations in the spatial resolution in the out-of-plane dimension. As a first indication of whether a dual-plane dual-view (DPDV) DTS data acquisition can yield a fair resolution in all three spatial dimensions, a manual registration between a frontal and a lateral image volume was performed. An anthropomorphic chest phantom was scanned frontally and laterally using a linear DTS acquisition, at 120 kVp. The reconstructed image volumes were resampled and manually co registered. Expert radiologist delineations of the mediastinal soft tissues enabled calculation of similarity metrics in regard to delineations in a reference CT volume. The fused volume produced the highest total overlap, implying that the fused volume was a more isotropic 3D representation of the examined object than the traditional chest DTS volumes. PMID- 26683463 TI - Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus in Ghana. AB - Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana. PMID- 26683465 TI - A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts. AB - Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal-lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal-lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts. PMID- 26683466 TI - Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age. AB - BACKGROUND: As part of the German Collaborative Study on Phenylketonuria (PKU)/Hyperphenylalaninaemia (HPA) Study Protocol, a Blaskovics protein loading test (180 mg phenylalanine (phe) protein equivalent per kg body weight and day for 72 h) had been applied to 145 children at the age of 6 months. For investigating possible age-related changes of metabolic phenotype, 51 of them received a 2nd loading test at 5 years of age. METHODS: Besides the analysis of blood phe levels, acidic phe transamination metabolites were quantified in urine. RESULTS: Compared to the 6-month data, the mean blood phe level 72 h after start of loading (Phe72) was found to be decreased by 7% (P = 0.06), whereas the mean urinary excretion (per 1.73 m2 body surface and day) of 2-hydroxyphenylacetic acid was increased 1.9-fold (P < 0.01). Corresponding with these analytical data, the kinetic model constant k out of metabolic plus renal phe disposal was found increased 1.3-fold in mean (P < 0.01).In 3 of the 51 patients, Phe72 was very high at 6 months while in the medium range at 5 years, suggesting that catabolic states may mimic a more severe metabolic defect.The blood phe level response of mild PKU (type II) was assigned identically at both ages in 7/9 patients. Diverging results were (i) response type III (mild hyperphenylalaninaemia) at 6 months and type II at 5 years and (ii) type II at 6 months and type III at age 5. CONCLUSION: Renal elimination of OHPAA and phe tolerance increase significantly between the age of 6 months and 5 years, suggesting that, at least in childhood, formation and/or renal disposal of phe transamination metabolites may be major distal determinants of phe tolerance. PMID- 26683467 TI - The Lactose and Galactose Content of Cheese Suitable for Galactosaemia: New Analysis. AB - INTRODUCTION: The UK Medical Advisory Panel of the Galactosaemia Support Group report the lactose and galactose content of 5 brands of mature Cheddar cheese, Comte and Emmi Emmental fondue mix from 32 cheese samples. The Medical Advisory Panel define suitable cheese in galactosaemia to have a lactose and galactose content consistently below 10 mg/100 g. METHODS: A total of 32 samples (5 types of mature Cheddar cheese, Comte and "Emmi Swiss Fondue", an emmental fondue mix) were analysed by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) technology used to perform lactose and galactose analysis. RESULTS: Cheddar cheese types: Valley Spire West Country, Parkham, Lye Cross Vintage, Lye Cross Mature, Tesco West Country Farmhouse Extra Mature and Sainsbury's TTD West Country Farmhouse Extra Mature had a lactose and galactose content consistently below 10 mg/100 g (range <0.05 to 12.65 mg). All Comte samples had a lactose content below the lower limit of detection (<0.05 mg) with galactose content from <0.05 to 1.86 mg/100 g; all samples of Emmi Swiss Fondue had lactose below the lower limit of detection (<0.05 mg) and galactose between 2.19 and 3.04 mg/100 g. CONCLUSIONS: All of these cheese types were suitable for inclusion in a low galactose diet for galactosaemia. It is possible that the galactose content of cheese may change over time depending on its processing, fermentation time and packaging techniques. PMID- 26683468 TI - The effects of different environmental pH on healing of tympanic membrane: an experimental study. AB - In this study, we investigated the effect of environmental pH on healing of acute rat tympanic membrane perforations. Twenty Wistar albino rats were divided into four groups and used in the study. A large myringotomy was performed in the posteroinferior quadrants of both tympanic membranes. In left ears, topical pH 4 standard calibration solution was used in groups 1 and 3, and pH 7 standard calibration solution was used in groups 2 and 4. Right ears served as controls, and allowed for spontaneous healing. The solutions were applied for 2 days in groups 1 and 2, and for 7 days in groups 3 and 4. Healing was assessed by macroscopic closure of the tympanic membrane perforation, and histopathological analysis of lamina propria edema, neovascularization, inflammatory cells, and fibroblastic reaction in the temporal bones. pH 7 and pH 4 groups were similar for macroscopic closure of perforation on day 2; however difference was significant on day 7. The fibroblastic activity was significantly less on days 2 and 7 in pH 4 group. On day 7, there were significant differences between pH 4 and pH 7, and pH 7 and control groups for inflammatory cell infiltration. In conclusion, clinical and histopathological results of this study indicated that acidic environmental pH speeded up and shortened wound-healing process. By building up optimum environmental pH, a healthy healing may be achieved in acute tympanic membrane perforations. PMID- 26683469 TI - Clinical and surgical implications regarding morphometric variations of the medial wall of the orbit in relation to age and gender. AB - The ethmoidal foramens are located on the medial wall of the orbit and are key reference points for intraoperative orientation. Detailed knowledge of the anatomy, bony landmarks and morphometric characteristics of the medial wall of the orbit is essential for various surgical procedures. The aim of this study was to determine the morphometric variations in the medial wall of the orbit and establish significant variations regarding age and gender. A total of 110 orbits were analyzed and subdivided by age (over or under 40 years) and gender. The distances of the medial wall of the orbit between the anterior lacrimal crest, the ethmoidal foramen, the optic canal and the interforamina were determined. Safe surgical areas were sought. Statistical tests were used to determine the differences between groups. In men, there is a safe surgical area proximal to the anterior and posterior ethmoidal foramen. In women, this area is in the posterior third of the medial wall of the orbit between the posterior ethmoidal foramen and the optic canal. Regarding variation according to age, the results of this study suggested that the anteroposterior diameter of the medial wall increases with age. This study showed that the anteroposterior total length of the medial orbit wall is similar between genders of similar age, increases with age, and has significant variations in the distances between the various structures that make up the medial orbit wall with regard to gender and age. PMID- 26683470 TI - Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer. AB - During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n = 59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n = 47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n = 33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5 year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9 %, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p = 0.030). According to our results, the oncological outcomes of three different platinum based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment. PMID- 26683471 TI - Postoperative antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery: a retrospective cohort study. AB - Antibiotic prophylaxis is commonly used in head and neck oncologic surgery, due to the clean-contaminated nature of these procedures. There is a wide variety in the use of prophylactic antibiotics regarding the duration of application and the choice of agent. The purpose of this study was to determine whether short-term or long-term antibiotic prophylaxis has an impact on the development of head and neck surgical wound infection (SWI). Retrospective chart review was carried out in 418 clean-contaminated head and neck surgical oncology cases at our department. More than 50 variables including tumour type and stage, type of surgical treatment, co-morbidities, duration and choice of antibiotic prophylaxis, and the incidence of SWI were analysed. Following descriptive data analysis, Chi square test by Pearson and Fisher's exact test were used for statistical evaluation. Fifty-eight of the 418 patients (13.9 %) developed SWI. Patients with advanced disease and tracheotomy showed a significantly higher rate of SWI than those with early stage disease and without tracheotomy (p = 0.012 and p = 0.00017, respectively). However, there was no significant difference between the SWI rates in the short term and long term treatment groups (14.6 and 13.2 %, respectively; p = 0.689). Diabetes and body weight were not found to be risk factors for SWI. Long-term antibiotic prophylaxis was not associated with a decrease in SWI in the entire cohort of patients undergoing clean-contaminated major head and neck oncologic surgery. Our data confirmed the extent of surgery and tracheotomy as being risk factors for postoperative SWI. PMID- 26683472 TI - Extracorporeal life support and survival after out-of-hospital cardiac arrest in a nationwide registry: A propensity score-matched analysis. AB - BACKGROUND: The benefit of extracorporeal life support (ECLS) in highly selective patients with out-of-hospital cardiac arrest (OHCA) is supported by previous studies; however, it is unclear whether the effects of ECLS are observed at a population level. This study aimed to determine whether ECLS is associated with improved survival outcomes compared to conventional CPR (cardiopulmonary resuscitation) at a national level. METHODS: We used a Korean national OHCA cohort database from 2009 to 2013. The inclusion criteria were OHCA adults with presumed cardiac aetiology and resuscitation by emergency medical services (EMS). Patients were excluded if their information on prehospital time intervals or clinical outcomes at hospital discharge was incomplete or not captured. The primary outcome was neurologically favourable survival to discharge. We compared the primary outcomes between the ECLS and non-ECLS groups using a multivariable logistic regression and a propensity score matching analysis. RESULTS: Of the 119,077 patients with OHCA, 36,547 were included in the analysis. There were 320 patients who received ECLS. There was no significant difference in neurologically favourable survival to discharge between the ECLS group and the non-ECLS group after adjusting for covariates (adjusted OR, 0.65; 95% CI, 0.41-1.04). In the propensity score-matched cohort, there was also no significant difference between the two groups (adjusted OR, 0.94; 95% CI, 0.41-2.14). CONCLUSIONS: In this propensity score-matched cohort using a nationwide OHCA database, OHCA victims who received ECLS did not show better survival outcomes than those who did not receive ECLS. PMID- 26683473 TI - Challenges of a community based pragmatic, randomised controlled trial of weight loss maintenance. AB - BACKGROUND: Randomised controlled trials (RCTs) have a reputation for being inherently difficult to deliver as planned and often face unforeseen challenges and delays, particularly in relation to organisational and governance difficulties, participant interest, constraints due to allocation of costs, local investigator interest and lengthy bureaucracy. Recruitment is often difficult and the challenges faced often impact on the cost and delivery of a successful trial within the funded period. This paper reflects upon the challenges faced in delivering a pragmatic RCT of weight loss maintenance in a community setting and suggests some potential solutions. METHODS: The weight loss maintenance in adults trial aimed to evaluate the impact of a 12 month, individually tailored weight maintenance intervention on BMI 3 years from randomisation. Participants were recruited primarily from participant identification centres (PICs)-GP surgeries, exercise on referral schemes and slimming world. The intervention was delivered in community settings. A recruitment strategy implementation plan was drafted to address and monitor poor recruitment. RESULTS: Delays in opening and recruitment were experienced early on. Some were beyond the control of the study team such as; disagreement over allocation of national health service costs and PIC classification as well as difficulties in securing support from research networks. That the intervention was delivered in community settings was often at the root of these issues. Key items to address at the design stage of future trials include feasibility of eligibility criteria. The most effective element of the recruitment implementation plan was to refocus sources of recruitment and target only those who could fulfil the eligibility criteria immediately. CONCLUSIONS: Learnings from this trial should be kept in mind by those designing similar studies in the future. Considering potential governance, cost and research network support implications at the design stage of pragmatic trials of any community-based complex intervention is paramount. The appropriateness and viability of inclusion criteria also require careful consideration as does use of a targeted advertising strategy. TRIAL REGISTRATION: ISRCTN35774128, 12/01/2010. PMID- 26683474 TI - SEOM clinical guidelines in metastatic breast cancer 2015. AB - Metastatic breast cancer is essentially an incurable disease. However, recent advances have resulted in a significant improvement of overall survival. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with metastatic breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference. PMID- 26683476 TI - A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17. AB - Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendeen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant. PMID- 26683475 TI - Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury. AB - BACKGROUND: Repeated mild traumatic brain injuries, such as concussions, may result in cumulative brain damage, neurodegeneration and other chronic neurological impairments. There are currently no clinically available treatment options known to prevent these consequences. However, growing evidence implicates neuroinflammation and oxidative stress in the pathogenesis of repetitive mild brain injuries; thus, these may represent potential therapeutic targets. Progesterone has been demonstrated to have potent anti-inflammatory and anti oxidant properties after brain insult; therefore, here, we examined progesterone treatment in rats given repetitive mild brain injuries via the repeated mild fluid percussion injury model. METHODS: Male Long-Evans rats were assigned into four groups: sham injury + vehicle treatment, sham injury + progesterone treatment (8 mg/kg/day), repeated mild fluid percussion injuries + vehicle treatment, and repeated mild fluid percussion injuries + progesterone treatment. Rats were administered a total of three injuries, with each injury separated by 5 days. Treatment was initiated 1 h after the first injury, then administered daily for a total of 15 days. Rats underwent behavioural testing at 12-weeks post treatment to assess cognition, motor function, anxiety and depression. Brains were then dissected for analysis of markers for neuroinflammation and oxidative stress. Ex vivo MRI was conducted in order to examine structural brain damage and white matter integrity. RESULTS: Repeated mild fluid percussion injuries + progesterone treatment rats showed significantly reduced cognitive and sensorimotor deficits compared to their vehicle-treated counterparts at 12-weeks post-treatment. Progesterone treatment significantly attenuated markers of neuroinflammation and oxidative stress in rats given repeated mild fluid percussion injuries, with concomitant reductions in grey and white matter damage as indicated by MRI. CONCLUSIONS: These findings implicate neuroinflammation and oxidative stress in the pathophysiological aftermath of mild brain injuries and suggest that progesterone may be a viable treatment option to mitigate these effects and their detrimental consequences. PMID- 26683477 TI - Erratum to: Complete chloroplast genome sequence of MD-2 pineapple and its comparative analysis among nine other plants from the subclass Commelinidae. PMID- 26683482 TI - Modelling and predicting the simultaneous growth of Escherichia coli and lactic acid bacteria in milk. AB - Modelling and predicting the simultaneous competitive growth of Escherichia coli and starter culture of lactic acid bacteria (Fresco 1010, Chr. Hansen, Horsholm, Denmark) was studied in milk at different temperatures and Fresco inoculum concentrations. The lactic acid bacteria (LAB) were able to induce an early stationary state in E. coli The developed model described and tested the growth inhibition of E. coli (with initial inoculum concentration 10(3) CFU/mL) when LAB have reached maximum density in different conditions of temperature (ranging from 12 C to 30 C) and for various inoculum sizes of LAB (ranging from approximately 10(3) to 10(7) CFU/mL). The prediction ability of the microbial competition model (the Baranyi and Roberts model coupled with the Gimenez and Dalgaard model) was first performed only with parameters estimated from individual growth of E. coli and the LAB and then with the introduced competition coefficients evaluated from co-culture growth of E. coli and LAB in milk. Both the results and their statistical indices showed that the model with incorporated average values of competition coefficients improved the prediction of E. coli behaviour in co culture with LAB. PMID- 26683478 TI - Comparing cognitive behavioural therapy for eating disorders integrated with behavioural weight loss therapy to cognitive behavioural therapy-enhanced alone in overweight or obese people with bulimia nervosa or binge eating disorder: study protocol for a randomised controlled trial. AB - BACKGROUND: Around 40 % of individuals with eating disorders of recurrent binge eating, namely bulimia nervosa and binge eating disorder, are obese. In contrast to binge eating disorder, currently there is no evidence base for weight management or weight loss psychological therapies in the treatment of bulimia nervosa despite their efficacy in binge eating disorder. Thus, a manualised therapy called HAPIFED (Healthy APproach to weIght management and Food in Eating Disorders) has been developed. HAPIFED integrates the leading evidence-based psychological therapies, cognitive behavioural therapy-enhanced (CBT-E) and behavioural weight loss treatment (BWLT) for binge eating disorder and obesity respectively. The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of HAPIFED versus CBT-E for people with bulimia nervosa and binge eating disorder who are overweight/obese. METHOD/DESIGN: A single-blind superiority RCT is proposed. One hundred Brazilian participants aged >= 18 years, with a diagnosis of bulimia nervosa or binge eating disorder, BMI > 27 to < 40 kg/m(2), will be recruited from both community and clinics and individually randomised to a therapy arm. Five groups of ten participants will receive the experimental intervention (HAPIFED) and the other five groups of ten the control intervention (CBT-E). Both therapies are manualised, and in this RCT will comprise 1 individual session and 29 office-based group sessions over 6 months. Assessment points will be at baseline, end of therapy, and 6 and 12 months after end of therapy. The primary outcome of this intervention will be reduced weight. Secondary outcomes will be improved metabolic indicators of weight management, reduction in eating disorder symptoms including improved control over eating, improved adaptive function, physical and mental health related quality of life, and reduced levels of depression and anxiety. DISCUSSION: This study will be the first to investigate a psychological therapy that aims to assist weight management in people with co-morbid overweight or obesity bulimia nervosa as well as with binge eating disorder. It will have the potential to improve health outcomes for the rapidly increasing number of adults with co-morbid obesity and binge eating disorder or bulimia nervosa. TRIAL REGISTRATION: US National Institutes of Health clinical trial registration number NCT02464345 , date of registration 1 June 2015. PMID- 26683483 TI - Natural additives to preserve quality and improve nutritional value of fresh-cut nectarine. AB - There is currently a high demand for natural and fresh-cut fruits. In this study, natural additives were applied to fresh-cut nectarines: (1) control, nontreated; (2) wedges were dipped in an antibrowning solution containing calcium ascorbate (AB); (3) and (4) wedges were dipped in an AB plus natural antimicrobial agents (vanillin or cinnamic acid, respectively). After these treatments, fresh-cut nectarines were packed and stored at 5 C for eight days. The treatments AB+Vanillin and AB+Cinnamic inhibited microbial counts when compared with control and AB-only samples. The application of these solutions did not impart any aromas or off-flavors to nectarines and maintained firmness during the shelf-life period. AB solutions inhibited polyophenol oxidase action and reduced browning while stabilizing the soluble phenolic content, increasing consumer's acceptance. Nectarine wedges assimilated the ascorbic acid from the AB solution and retained it during the shelf-life period. The combination of an antibrowning agent and natural antimicrobials helped to control microbiological growth while maintaining high-quality parameters. They can be an attractive "green" alternative for organic fresh-cut products to other chemical sanitizers such as chlorine. PMID- 26683484 TI - Predicting bacterial growth in raw, salted, and cooked chicken breast fillets during storage. AB - Growth curves were evaluated for aerobic mesophilic and psychrotrophic bacteria, Pseudomonas spp. and Staphylococcus spp., grown in raw, salted, and cooked chicken breast at 2, 4, 7, 10, 15, and 20 C, respectively, using the modified Gompertz and modified logistic models. Shelf life was determined based on microbiological counts and sensory analysis. Temperature increase reduced the shelf life, which varied from 10 to 26 days at 2 C, from nine to 21 days at 4 C, from six to 12 days at 7 C, from four to eight days at 10 C, from two to four days at 15 C, and from one to two days at 20 C. In most cases, cooked chicken breast showed the highest microbial count, followed by raw breast and lastly salted breast. The data obtained here were useful for the generation of mathematical models and parameters. The models presented high correlation and can be used for predictive purposes in the poultry meat supply chain. PMID- 26683485 TI - Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003. AB - Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi-centre, prospective, randomized phase III trial, investigating treatment intensification or de-escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7.3%) were aged 16-24 years. These patients were significantly more likely to have high risk MRD compared to 10-15 year olds (47.9% vs. 36.6%, P = 0.004). Nonetheless, 5-year event-free survival for the TYA cohort (aged 16-24 years) was 72.3% [95% confidence interval (CI): 66.2-78.4] overall and 92.6% (95% CI: 85.5-99.7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged >=10 years compared to those aged 9 or younger (P < 0.0001) and novel age-specific patterns of treatment related toxicity were observed. TYA patients obtain excellent outcomes with a risk- and response-adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities. PMID- 26683486 TI - Effects of pharmaceutical formulations containing thyme on carbon tetrachloride induced liver injury in rats. AB - BACKGROUND: Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats. METHODS: Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining. RESULTS: Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals. CONCLUSIONS: Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated. PMID- 26683487 TI - What do people with MS want from a web-based resource to encourage increased physical activity behaviour? AB - PURPOSE: To investigate what people with multiple sclerosis (PwMS) want from a web-based resource that encourages physical activity (PA). METHODS: Three focus groups (n = 22) and 11 semi-structured interviews were conducted. The semi structured interviews were conducted using Skype (audio only) or telephone. Interviews were audio-recorded, transcribed verbatim and the thematic analysis approach described by Braun and Clarke was performed. RESULTS: The themes from the data were: (1) Content - important information to include, (2) Presentation - varying format, different abilities, (3) Interactivity - build a sense of community and (4) Reach the Audience - let people know. Participants believed the web resource to be a good idea and suggested that the content of resource should include a focus on the knowledge of the benefits of being physically active. Illustrating the types of exercise in which PwMS could participate in was also discussed. Ensuring information was stratified by mobility level and that the resource was interactive, portraying a 'Sense of Community' and use of success stories, was also suggested by participants. CONCLUSIONS: The data suggest that PwMS want a variety of information from a variety of sources and that this information is to be both stratified and interactive. These results will be used to inform the development of the 'Activity Matters' website which will aim to enable PwMS to become more physically active. Implications for Rehabilitation People with multiple sclerosis (PwMS) want information on the benefits of being physically active in order to change physical inactivity behaviours. Offering PwMS a range of exercise options that can be stratified by mobility and physical activity levels may further enable them to become more physically active. Peer support and creating a sense of community are important components when aiming to motivate PwMS to become more physically active. PMID- 26683488 TI - Long-Term Nationwide Follow-Up Study of Simple Congenital Heart Disease Diagnosed in Otherwise Healthy Children. AB - BACKGROUND: Systematic follow-up is currently not recommended for patients with simple congenital heart disease; however, only a few data exist on the long-term prognosis of simple congenital heart disease. METHODS AND RESULTS: We undertook a nationwide follow-up study of a cohort of 1241 simple congenital heart disease patients, diagnosed from 1963 through 1973, in otherwise healthy children and alive at 15 years of age. We identified 10 age- and sex-matched general population controls per patient. We followed the study population through Danish public registries from the age of 15 years up to January 1, 2013 with respect to mortality, cause of death, morbidity, and medical follow-up. The patients were followed for a total of 58 422 patient-years and had a median age at the end of follow-up of 47.4 years (interquartile range, 43.5-50.9). Mortality was increased compared with the general population, both overall (adjusted hazard ratio [aHR],1.9; 95% confidence interval [CI], 1.5-2.4)] and for patients (79%) without medical follow-up (aHR, 1.7; 95% CI, 1.3-2.2). The most common cause of death (40%) was sudden unexpected death (aHR, 4.3; 95% CI, 2.9-6.5). The incidence of critical cardiac morbidity was 3.9 per 1000 patient-years with the most frequent events being an adult (re)operation and hospitalization for heart failure or ventricular tachyarrhythmia. This corresponded to an aHR of 5.7 (95% CI, 4.6-6.9) when compared with the general population. CONCLUSIONS: Patients diagnosed with simple congenital heart disease in the 1960s have substantially increased long term mortality and cardiac morbidity compared with the general population. Further studies on the effectiveness of systematic medical follow-up programs appear warranted. PMID- 26683489 TI - Twist of Fate for Simple Congenital Heart Defects. PMID- 26683491 TI - Effects of replacing groundnut cake with rumen content supplemented with or without enzyme in the diet of weaner rabbits. AB - BACKGROUND: Rabbits are also herbivores which efficiently convert fodder to food. They are prolific and converter of plant proteins of little or no use to people as food into high-value animal protein. Rabbit meat is high in protein, low in calories and low in fat and cholesterol contents, being considered as a delicacy and a healthy food product. Feeding rabbits with concentrates is expensive and therefore in order to reduce cost of production, hence the use of rumen content in this study as alternative feedstuff without competition. METHODS: A total of thirty six (36) weaner rabbits (oryctalagus cuniculus) of different body weight and age where use in this experiment to determine the effects of replacing rumen content with or without enzyme supplementation for groundnut cake. This feeding trial which lasted for 8 weeks was carried out in order to determine the replacement value of groundnut cake with rumen content with or without enzyme in the diet of weaner rabbit. A 3x2 factorial experiment was adopted such that there where three (3) replacement level of rumen content (0, 25 and 50 %) for groundnut cake by two supplemental level (no enzyme and enzyme supplement). RESULTS: The results showed that increased inclusion level of rumen content has significant effects (p < 0.05) on daily feed intake, rate of weight gain, feed to gain ratio, nitrogen retention, faecal nitrogen, total nitrogen output and nitrogen digestibility. The weight gained by rabbits fed on 0, 25 and 50 % were all comparable (p > 0.05) with weight gained value of 7.62,7.44 and 7.36 g respectively. Similarly there was a significant (p < 0.05) effect of supplement added on the body weight gain of the experimental animals. There was significant effect (p < 0.05) of the diet on the obtained feed to gain ratio. However, there was no significant effect (p > 0.05) of the treatment on urinary nitrogen. Significant (p < 0.05) effects of supplementation was observed on the feed intake, weight gain, feed to gain ratio, faecal nitrogen, nitrogen retention and nitrogen digestibility but there was no significant effects (p > 0.05) of the supplementation on the nitrogen intake. The interaction between the varying levels of rumen content supplementation had significant effects (p < 0.05) on the feacal nitrogen, feed intake and feed to gain ratio but no significant (p < 0.05) effects on interaction of nitrogen intake. CONCLUSION: In conclusion, since the results from this study showed no negative effects on the performance of the experimental animals, the test ingredient can be used as alternative feedstuff at a lower inclusion level so as to reduce production cost and expand rabbit production. PMID- 26683490 TI - The Essential Complexity of Auditory Receptive Fields. AB - Encoding properties of sensory neurons are commonly modeled using linear finite impulse response (FIR) filters. For the auditory system, the FIR filter is instantiated in the spectro-temporal receptive field (STRF), often in the framework of the generalized linear model. Despite widespread use of the FIR STRF, numerous formulations for linear filters are possible that require many fewer parameters, potentially permitting more efficient and accurate model estimates. To explore these alternative STRF architectures, we recorded single unit neural activity from auditory cortex of awake ferrets during presentation of natural sound stimuli. We compared performance of > 1000 linear STRF architectures, evaluating their ability to predict neural responses to a novel natural stimulus. Many were able to outperform the FIR filter. Two basic constraints on the architecture lead to the improved performance: (1) factorization of the STRF matrix into a small number of spectral and temporal filters and (2) low-dimensional parameterization of the factorized filters. The best parameterized model was able to outperform the full FIR filter in both primary and secondary auditory cortex, despite requiring fewer than 30 parameters, about 10% of the number required by the FIR filter. After accounting for noise from finite data sampling, these STRFs were able to explain an average of 40% of A1 response variance. The simpler models permitted more straightforward interpretation of sensory tuning properties. They also showed greater benefit from incorporating nonlinear terms, such as short term plasticity, that provide theoretical advances over the linear model. Architectures that minimize parameter count while maintaining maximum predictive power provide insight into the essential degrees of freedom governing auditory cortical function. They also maximize statistical power available for characterizing additional nonlinear properties that limit current auditory models. PMID- 26683492 TI - Horizontal Transfer of Plasmid-Mediated Cephalosporin Resistance Genes in the Intestine of Houseflies (Musca domestica). AB - Houseflies are a mechanical vector for various types of bacteria, including antimicrobial-resistant bacteria (ARB). If the intestine of houseflies is a suitable site for the transfer of antimicrobial resistance genes (ARGs), houseflies could also serve as a biological vector for ARB. To clarify whether cephalosporin resistance genes are transferred efficiently in the housefly intestine, we compared with conjugation experiments in vivo (in the intestine) and in vitro by using Escherichia coli with eight combinations of four donor and two recipient strains harboring plasmid-mediated cephalosporin resistance genes and chromosomal-encoded rifampicin resistance genes, respectively. In the in vivo conjugation experiment, houseflies ingested donor strains for 6 hr and then recipient strains for 3 hr, and 24 hr later, the houseflies were surface sterilized and analyzed. In vitro conjugation experiments were conducted using the broth-mating method. In 3/8 combinations, the in vitro transfer frequency (Transconjugants/Donor) was >=1.3 * 10(-4); the in vivo transfer rates of cephalosporin resistance genes ranged from 2.0 * 10(-4) to 5.7 * 10(-5). Moreover, cephalosporin resistance genes were transferred to other species of enteric bacteria of houseflies such as Achromobacter sp. and Pseudomonas fluorescens. These results suggest that houseflies are not only a mechanical vector for ARB but also a biological vector for the occurrence of new ARB through the horizontal transfer of ARGs in their intestine. PMID- 26683493 TI - Can Nonnative Speakers Reduce English Vowels in a Native-Like Fashion? Evidence from L1-Spanish L2-English Bilinguals. AB - This paper investigates the production of English unstressed vowels by two groups of early (ESp) and late Spanish (LSp) bilinguals and a control group of native English (NE) monolinguals. Three acoustic measurements were obtained: duration and intensity ratios of unstressed to stressed vowels, normalized vowel formants and euclidean distances. Both groups of bilinguals showed significantly fewer differences in duration between stressed and unstressed vowels than the NE monolinguals. Intensity differences depended on whether the stress pattern of the target English words matched the stress pattern of their Spanish cognates. As for vowel quality, the early bilinguals reduced the unstressed vowels, which clustered around the midcenter area of the vowel space, in the same fashion as the NE monolinguals, suggesting that vowel reduction might be operating at the phonological level. However, the late bilinguals showed a context-dependent, phonetic-level pattern with vowels that were more peripheral in the vowel space. PMID- 26683494 TI - Long-Range Conformational Response of a PDZ Domain to Ligand Binding and Release: A Molecular Dynamics Study. AB - The binding of a ligand to a protein may induce long-range structural or dynamical changes in the biomacromolecule even at sites physically well separated from the binding pocket. A system for which such behavior has been widely discussed is the PDZ2 domain of human tyrosine phosphatase 1E. Here, we present results from equilibrium trajectories of the PDZ2 domain in the free and ligand bound state, as well as nonequilibrium simulations of the relaxation of PDZ2 after removal of its peptide ligand. The study reveals changes in inter-residue contacts, backbone dihedral angles, and C(alpha) positions upon ligand release. Our findings show a long-range conformational response of the PDZ2 domain to ligand release in the form of a collective shift of the secondary structure elements alpha2, beta2, beta3, alpha1-beta4, and the C terminal loop relative to the rest of the protein away from the N-terminus, and a shift of the loops beta2 beta3 and beta1-beta2 in the opposite direction. The shifts lead to conformational changes in the backbone, especially in the beta2-beta3 loop but also in the beta5-alpha2 and the alpha2-beta6 loop, and are accompanied by changes of inter-residue contacts mainly within the beta2-beta3 loop as well as between the alpha2 helix and other segments. The residues showing substantial changes of inter-residue contacts, backbone conformations, or C(alpha) positions are considered "key residues" for the long-range conformational response of PDZ2. By comparing these residues with various sets of residues highlighted by previous studies of PDZ2, we investigate the statistical correlation of the various approaches. Interestingly, we find a considerable correlation of our findings with several works considering structural changes but no significant correlations with approaches considering energy flow or networks based on inter-residue energies. PMID- 26683495 TI - Recent Advances in Hydrocortisone Replacement Treatment. AB - Since the first use of cortisone in patients around 65 years ago, the use of synthetic glucocorticoids has made a crucial impact on the treatment of several diseases in medicine. Although significant reductions in morbidity and mortality have occurred in patients suffering from cortisol deficiency, conventional hydrocortisone replacement treatment is still inadequate. A major limitation is that it fails to replace cortisol in a physiological manner. Cortisol has a distinct circadian rhythm and acts as a secondary messenger synchronizing the central to peripheral clocks, hence playing a key role in biological processes and the circadian timing system. Circadian misalignment has been associated with ill-health and so nonphysiological glucocorticoid treatment could explain the increased mortality rate, poor quality of life and metabolic complications in patients suffering from adrenal insufficiency. Attempts at replacing cortisol in a physiological manner have shown significant progress in the past decade with the development of modified-release formulations of hydrocortisone (Chronocort(r) and Plenadren(r)) and continuous subcutaneous hydrocortisone infusions. Initial studies investigating the use of these replacement regimens are promising, demonstrating both clinical and biochemical improvement. Larger studies are needed to determine whether this novel approach enhances long-term outcomes in both children and adults with cortisol deficiency. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel. PMID- 26683496 TI - Collective excitations in Na2IrO3. AB - We study the collective excitations of Na2IrO3 in an itinerant electron approach. We consider a multi-orbital tight-binding model with the electron transfer between the Ir 5d states mediated via oxygen 2p states and the direct d-d transfer on a honeycomb lattice. The one electron energy as well as the ground state energy are investigated within the Hartree-Fock approximation. When the direct d-d transfer is weak, we obtain nearly flat energy bands due to the formation of quasimolecular orbitals, and the ground state exhibits the zigzag spin order. The evaluation of the density-density correlation function within the random phase approximation shows that the collective excitations emerge as bound states. For an appropriate value of the direct d-d transfer, some of them are concentrated in the energy region omega<50 meV(magnetic excitations) while the others lie in the energy region omega>350 meV (excitonic excitations). This behaviour is consistent with the resonant inelastic x-ray scattering spectra. We also show that the larger values of the direct d-d transfer are unfavourable in order to explain the observed aspects of Na2IrO3 such as the ordering pattern of the ground state and the excitation spectrum. These findings may indicate that the direct d-d transfer is suppressed by the structural distortions in the view of excitation spectroscopy, as having been pointed out in the ab initio calculation. PMID- 26683497 TI - Regioselective Rhodium-Catalyzed Addition of 1,3-Dicarbonyl Compounds to Terminal Alkynes. AB - A new method for the rhodium-catalyzed regioselective C-C bond formation using terminal alkynes and 1,3-dicarbonyl compounds to achieve valuable branched alpha allylated 1,3-dicarbonyl products is reported. With a Rh(I)/DPEphos/p-CF3-benzoic acid as the catalyst system, the desired products can be obtained in good to excellent yields and with perfect regioselectivity. A broad range of functional groups were tolerated, and first experimental insights of a plausible reaction mechanism were obtained. PMID- 26683498 TI - A new prognostic scoring system using factors available preoperatively to predict survival after operative resection of perihilar cholangiocarcinoma. AB - BACKGROUND: Perihilar cholangiocarcinoma has one of the poorest prognoses of all cancers. However, mortality and morbidity rates after surgical resection are 0 15% and 14-66%, respectively. Additionally, the 5-year overall survival rates are reported at 22-40%. These findings indicate that only selected patients achieve satisfactory beneficial effects from operative treatment. This retrospective study sought to investigate preoperatively available prognostic factors and establish a new preoperative staging system to predict survival after major hepatectomy of perihilar cholangiocarcinoma. PATIENTS AND METHODS: We evaluated 121 consecutive patients who underwent operative exploration for perihilar cholangiocarcinoma. RESULTS: Univariate and multivariate analysis using the identified preoperative factors revealed that 4 factors (platelet-lymphocyte ratio [PLR] > 150, serum C-reactive protein [CRP] levels > 0.5 mg/dL, albumin levels < 3.5 g/dL, and carcinoembryonic antigen [CEA] levels > 7.0 ng/mL) were independent prognostic factors of postoperative survival. These 4 preoperative factors were allocated 1 point each. The total score was defined as the Preoperative Prognostic Score (PPS). Patients with a PPS of 0, 1, 2, or 3/4 had a 5-year survival of 84.3%, 51.3%, 46.4%, and 0%, respectively. There were also differences in the 5-year survival according to the PPS (0 vs 1 [P = .013] and 2 vs 3/4 [P < .001]). Patients with a total PPS of 3/4 had a dismal prognosis, with a median survival of 11.3 months. CONCLUSION: A new preoperative scoring system using PLR, serum CRP, albumin, and CEA levels could predict postoperative survival resection of perihilar cholangiocarcinoma. PMID- 26683499 TI - Cervical dilation before first-trimester surgical abortion (<14 weeks' gestation). AB - First-trimester surgical abortion is a common, safe procedure with a major complication rate of less than 1%. Cervical dilation before suction abortion is usually accomplished using tapered mechanical dilators. Risk factors for major complications in the first trimester include increasing gestational age and provider inexperience. Cervical priming before first-trimester surgical abortion has been studied using osmotic dilators and pharmacologic agents, most commonly misoprostol. Extensive data demonstrate that a variety of agents are safe and effective at causing preoperative cervical softening and dilation; however, given the small absolute risk of complications, the benefit of routine use of misoprostol or osmotic dilators in first-trimester surgical abortion is unclear. Although cervical priming results in reduced abortion time and improved provider ease, it requires a delay of at least 1 to 3 h and may confer side effects. The Society of Family Planning does not recommend routine cervical priming for first trimester suction abortion but recommends limiting consideration of cervical priming for women at increased risk of complications from cervical dilation, including those late in the first trimester, adolescents and women in whom cervical dilation is expected to be challenging. PMID- 26683500 TI - Quantitative Aspects of the Interfacial Catalytic Oxidation of Dithiothreitol by Dissolved Oxygen in the Presence of Carbon Nanoparticles. AB - The catalytic nature of particulate matter is often advocated to explain its ability to generate reactive oxygen species, but quantitative data are lacking. We have performed molecular characterization of three different carbonaceous nanoparticles (NP) by 1. identifying and quantifying their surface functional groups based on probe gas-particle titration; 2. studying the kinetics of dissolved oxygen consumption in the presence of suspended NP's and dithiothreitol (DTT). We show that these NP's can reversibly change their oxidation state between oxidized and reduced functional groups present on the NP surface. By comparing the amount of O2 consumed and the number of strongly reducing sites on the NP, its average turnover ranged from 35 to 600 depending on the type of NP. The observed quadratic rate law for O2 disappearance points to a Langmuir Hinshelwood surface-based reaction mechanism possibly involving semiquinone radical. In the proposed model, the strongly reducing surface site is assumed to be a polycyclic aromatic hydroquinone whose oxidation to the corresponding conjugated quinone is rate-limiting in the catalytic chain reaction. The presence and strength of the reducing surface functional groups are important for explaining the catalytic activity of NP in the presence of oxygen and a reducing agent like DTT. PMID- 26683501 TI - Reducing the Incidence of Cast-related Skin Complications in Children Treated With Cast Immobilization. AB - BACKGROUND: Cast immobilization remains the mainstay of pediatric orthopaedic care, yet little is known about the incidence of cast-related skin complications in children treated with cast immobilization. The purposes of this quality improvement project were to: (1) establish a baseline rate of cast-related skin complications in children treated with cast immobilization, (2) identify trends in children who experienced cast-related skin complications, (3) design an intervention aimed at decreasing the rate of cast-related skin complications, and (4) determine the effectiveness of the intervention. METHODS: A prospective interrupted time-series design was used to determine the incidence of cast related skin complications overtime and compare the rates of skin complications before and after an intervention designed to decrease the incidence of cast related heel complications. All consecutive patients who were treated with cast immobilization from September 2012 to September 2014 were included. A cast related skin complications data collection tool was used to capture all cast related skin complications. A high rate of heel events was noted in our preliminary analysis and an intervention was designed to decrease the rate of cast-related skin complications, including the addition of padding during casting and respective provider education. RESULTS: The estimated cast-related skin events rate for all patients was 8.9 per 1000 casts applied. The rate for the total preintervention sample was 13.6 per 1000 casts which decreased to 6.6 in the postintervention sample. When examining the heel-only group, the rate was 17.1 per 1000 lower extremity casts applied in the preintervention group and 6.8 in the postintervention group. CONCLUSIONS: Incorporating padding to the heel of lower extremity cast was an effective intervention in decreasing the incidence of cast-related skin complications in patients treated with cast immobilization. LEVEL OF EVIDENCE: Level II. PMID- 26683502 TI - Upper Cervical Fusion in Children With Spondyloepiphyseal Dysplasia Congenita. AB - BACKGROUND: Paraplegia or death secondary to upper cervical spine instability and spinal cord compression are known consequences of spondyloepiphyseal dysplasia congenita (SEDC). Stabilization and occasionally decompression of the upper cervical spine are indicated to treat upper cervical instability and stenosis. The purpose of this study was to report the results of upper cervical spine fusion in children with SEDC who had upper cervical instability. METHODS: Twenty children (17 females and 3 males) with SEDC who underwent upper cervical spine fusion at a mean age of 72 months were retrospectively analyzed. Three of these children were under the age of 2. Fifteen children had posterior instrumentation and fusion whereas 5 children had posterior in situ fusion without use of any implant. Thirteen of 20 children had iliac crest autograft. Radiographic and clinical results were reported. RESULTS: The average follow-up period was 8 years and 8 months. All children with instrumentation achieved fusion. Three of 5 children who had no instrumentation had nonunion (1 child had a stable nonunion and did not need revision; 1 had a single noninstrumented revision and ended up with a stable nonunion without further intervention; and the third one had a noninstrumented revision and had to have a second, instrumented, revision to achieve fusion). Six children had thoracolumbar scoliosis or kyphoscoliosis which required surgical management.No postoperative neurological deficits were observed. Two of the 3 children with a preoperative neurological deficit showed full recovery and the third one remained unchanged. Pseudarthrosis is the main complication for the noninstrumented group. Distal junctional instability after successful fusion is seen at long-term follow-up (average=6 y) for 13% of patients in instrumented group. CONCLUSIONS: Instrumentation and iliac bone grafting results in 100% upper cervical fusion for SEDC children who demonstrated instability before surgery. LEVEL OF EVIDENCE: Level IV-therapeutic. PMID- 26683503 TI - Why No Signals? Cerebral Anatomy Predicts Success of Intraoperative Neuromonitoring During Correction of Scoliosis Secondary to Cerebral Palsy. AB - BACKGROUND: Intraoperative neuromonitoring (IONM) is widely used to reduce postoperative neurological complications during scoliosis correction. IONM allows intraoperative detection of neurological insults to the spinal cord and enables surgeons to react in real time. IONM failure rates can reach 61% in patients with cerebral palsy (CP). Factors decreasing the quality of IONM signals or making IONM impossible in CP patients undergoing scoliosis correction have not been well described. METHODS: We categorized IONM data from 206 children with CP who underwent surgical scoliosis correction at a single institution from 2002 through 2013 into 3 groups: (1) "no signals," if neither somatosensory-evoked potentials (SSEP) nor transcranial motor-evoked potentials (TcMEP) could be obtained; (2) "no sensory," if no interpretable SSEP were obtained regardless of interpretable TcMEP; and (3) "no motor," if no interpretable TcMEP were obtained regardless of interpretable SSEP. We analyzed preexisting neuroimaging, available for 93 patients, and neurological status of the full cohort against these categories. Statistical analysis of univariate and multivariate associations was performed using logistic regression. Odds ratios (ORs) were calculated with significance set at P<0.05. RESULTS: Multivariate analysis showed significant associations of periventricular leukomalacia (PVL), hydrocephalus, and encephalomalacia with lack of meaningful and interpretable signals. Focal PVL (Fig. 1) was associated with no motor (OR=39.95; P=0.04). Moderate hydrocephalus was associated with no signals (OR=32.35; P<0.01), no motor (OR=10.14; P=0.04), and no sensory (OR=8.44; P=0.03). Marked hydrocephalus (Fig. 2) was associated with no motor (OR=20.46; P<0.01) and no signals (OR=8.83; P=0.01). Finally, encephalomalacia (Fig. 3) was associated with no motor (OR=6.99; P=0.01) and no signals (OR=4.26; P=0.03). CONCLUSION: Neuroanatomic findings of PVL, hydrocephalus, and encephalomalacia are significant predictors of limited IONM signals, especially TcMEP. LEVEL OF EVIDENCE: Level IV. PMID- 26683504 TI - Adolescent Distal Humerus Fractures: ORIF Versus CRPP. AB - BACKGROUND: Although supracondylar humerus fractures are common in young children, the incidence in adolescents is much lower. As a result, there is a paucity of literature to guide treatment. The purpose of this study was to review the treatment and outcomes for a consecutive series of distal humerus fractures in adolescents and to compare outcomes between patients treated with percutaneous skeletal fixation and those treated with open reduction and fixation. METHODS: A retrospective review of patients 10 to 17 years of age who underwent surgical treatment for a distal humerus fracture from 2005 to 2014 was performed. Patients with medial epicondyle fractures and those with insufficient follow-up to document union or return of motion were excluded. Medical records were reviewed to collect demographic data as well as operative approach and method of fixation. Clinical outcomes included range of motion, time to maximum motion, and complications [nerve dysfunction, heterotopic ossification (HO), need for secondary surgery]. Radiographs were reviewed to determine time to union as well as coronal and sagittal alignment. RESULTS: One hundred eighteen adolescents with displaced distal humerus fractures were identified. Eighty-one met inclusion criteria. Forty-four of these were classified as extra-articular [Orthopaedic Trauma Association (OTA) 13-A], and 37 were intra-articular fractures (10 OTA 13 B and 27 OTA 13-C).Although not statistically significant, closed treatment with percutaneous fixation of extra-articular fractures resulted in greater flexion extension arc of motion at final follow-up (128 vs. 119 degrees, P=0.17) and demonstrated more rapid return of motion (2.8 vs. 3.9 mo, P=0.05) when compared with open treatment despite a longer duration of immobilization and less formal physical therapy. Complications such as HO (P=0.05), nerve dysfunction (P=0.02), and secondary surgery (P=0.001) were more common in the open treatment group.Closed treatment with percutaneous fixation of intra-articular fractures was performed in younger patients of similar size (12.8 vs. 14.4 y, P<0.01; 154 vs. 142 lbs, P=0.5). There were no significant differences between groups in regard to outcomes or complications. There were trends toward increased frequency of HO, nerve dysfunction, and secondary surgery in the open treatment group.Patients with intra-articular fractures were older (14.2 vs. 11.5 y, P<0.001) and heavier (144 vs. 94 lbs, P<0.001) than patients with extra-articular fractures and were more likely to be treated open (74% vs. 11%, P<0.001). Extra articular fractures demonstrated a greater total arc of motion (126 vs. 118 degrees, P=0.04) at final follow-up despite longer duration of immobilization (23 vs. 15 d, P=0.002), and less physical therapy (27% vs. 73%, P<0.001). Radiographic carrying angle (16.6 vs. 22.3 degrees, P=0.08) and anterior humeral line (95% vs. 81%, P=0.07) trended toward more anatomic alignment in the extra articular group. Secondary surgery was more common after intra-articular fracture (24% vs. 7%, P=0.03). CONCLUSIONS: Closed reduction and pinning of extra articular distal humerus fractures in adolescents resulted in predictable clinical and radiographic outcomes and allowed for earlier return of motion and fewer complications when compared with open treatment. Intra-articular distal humerus fractures occur more frequently in older adolescents and are more likely to require open reduction and internal fixation to obtain joint congruity. Patients with intra-articular injuries should be cautioned that regaining full elbow motion may be more difficult, and there is an increased risk for complications and need for additional surgery. Closed reduction and percutaneous fixation of intra-articular injuries appears to be a reasonable option in select patients. LEVEL OF EVIDENCE: Level III-retrospective comparative study. PMID- 26683505 TI - Advanced Containment With Triple Innominate Osteotomy in Legg-Calve-Perthes Disease: A Viable Option Even in Severe Cases. AB - BACKGROUND: Legg-Calve-Perthes disease (LCPD), in its severe form, remains a challenge. More recent classifications, particularly the modified Elizabethtown classification, have highlighted the chronologic stage of LCPD and its effect on surgical outcome. Hip severity and age of disease onset have also been shown to be powerful determinants of outcome. This study was performed to determine whether disease stage, disease severity, or patient age, are absolute indicators of whether a patient can benefit from surgical containment with triple innominate osteotomy (TIO). METHODS: All patients with LCPD treated with TIO between 1995 and 2011 were collected. Only those patients with a minimum of 2-year radiographic follow-up and no previous or concomitant femoral realignment surgery were included. Fifty-four patients (56 hips) met our inclusion criteria. The modified Elizabethtown classification was used to classify disease stage as early (=IIb). Catterall and lateral pillar classifications were used to classify disease severity, and the Stulberg classification was utilized for radiographic outcome, defined as good (I/II) or poor (III/IV/V). RESULTS: Fifty one males and 3 females with a mean chronological age at surgery of 8.2+/-1.8 years were included (2 bilateral cases). Mean follow-up was 72.8+/-30.2 months. There was no significant difference in the proportion of Stulberg good versus poor outcomes when comparing hips that were graded as early or late stage (P=0.842), or Catterall I and II versus III and IV (P=0.304). Although not statistically significant, patients with lateral pillars B and BC (P=0.076) and patients who were aged 8.0 and younger trended toward doing better compared with lateral pillar C and over age 8.0 (P=0.085), respectively. CONCLUSIONS: Radiographic results demonstrate that good outcomes are not entirely dependent on the stage of disease in LCPD when containment is performed with TIO. As expected, TIO appears to be more effective in younger patients with less severe disease. We conclude that even severely involved LCPD hips, independent of age, should be offered surgical containment. The failure rate in this group is higher, as expected, but many achieve good results and there are treatment methods available to those who fail containment. LEVEL OF EVIDENCE: Level IV. PMID- 26683506 TI - Pharmacodynamic Analysis of a Fluid Challenge. AB - OBJECTIVE: This study aims to describe the pharmacodynamics of a fluid challenge over a 10-minute period in postoperative patients. DESIGN: Prospective observational study. SETTING: General and cardiothoracic ICU, tertiary hospital. PATIENTS: Twenty-six postoperative patients. INTERVENTION: Two hundred and fifty milliliter fluid challenge performed over 5 minutes. Data were recorded over 10 minutes after the end of fluid infusion MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured with a calibrated LiDCOplus (LiDCO, Cambridge, United Kingdom) and Navigator (Applied Physiology, Sydney, Australia) to obtain the Pmsf analogue (Pmsa). Pharmacodynamics outcomes were modeled using a Bayesian inferential approach and Markov chain Monte Carlo estimation methods. Parameter estimates were summarized as the means of their posterior distributions, and their uncertainty was assessed by the 95% credible intervals. Bayesian probabilities for groups' effect were also derived. The predicted maximal effect on cardiac output was observed at 1.2 minutes (95% credible interval, -0.6 to 2.8 min) in responders. The probability that the estimated area under the curve of central venous pressure was smaller in nonresponders was 0.12. (estimated difference, -4.91 mm Hg.min [95% credible interval, -13.45 to 3.3 mm Hg min]). After 10 minutes, there is no evidence of a difference between groups for any hemodynamic variable. CONCLUSIONS: The maximal change in cardiac output should be assessed 1 minute after the end of the fluid infusion. The global effect of the fluid challenge on central venous pressure is greater in nonresponders, but not the change observed 10 minutes after the fluid infusion. The effect of a fluid challenge on hemodynamics is dissipated in 10 minutes similarly in both groups. PMID- 26683507 TI - Opportunities for Patient-centered Outcomes Research in Radiology. AB - Recently created in 2010, the Patient-Centered Outcomes Research Institute (PCORI) supports patient-centered comparative effectiveness research with a focus on prioritizing high-impact studies and improving trial design methodology. The Association of University Radiologists Radiology Research Alliance Task Force on patient-centered outcomes research in Radiology aims to review recently funded imaging-centric projects that adhere to the methodologies established by PCORI. We provide an overview of the successful application of PCORI standards to radiology topics, highlight how these methodologies differ from other forms of radiology research, and identify opportunities for new projects as well as potential barriers for involvement. Our hope is that review of specific case examples in radiology will clarify the use and value of PCORI methods mandated and supported nationally by the Affordable Care Act. PMID- 26683508 TI - Value of Imaging Part I: Perspectives for the Academic Radiologist. AB - With payers and policymakers increasingly scrutinizing the value of medical imaging, opportunities abound for radiologists and radiology health services researchers to meaningfully and rigorously demonstrate value. Part one of this two-part series on the value of imaging explores the concept of value in health care from the perspective of multiple stakeholders and discusses the opportunities and challenges for radiologists and health service researchers to demonstrate value. The current absence of meaningful national value metrics also presents an opportunity for radiologists to take the lead on the discussions of these metrics that may serve as the basis for future value-based payments. As both practitioners and investigators, radiologists should consider the perspectives of multiple stakeholders in all they do-interdisciplinary support and cooperation are essential to the success of value-focused imaging research and initiatives that improve patient outcomes. Radiology departments that align their cultures, infrastructures, and incentives to support these initiatives will greatly increase their chances of being successful in these endeavors. PMID- 26683509 TI - The Value of Imaging Part II: Value beyond Image Interpretation. AB - Although image interpretation is an essential part of radiologists' value, there are other ways in which we contribute to patient care. Part II of the value of imaging series reviews current initiatives that demonstrate value beyond the image interpretation. Standardizing processes, reducing the radiation dose of our examinations, clarifying written reports, improving communications with patients and providers, and promoting appropriate imaging through decision support are all ways we can provide safer, more consistent, and higher quality care. As payers and policy makers push to drive value, research that demonstrates the value of these endeavors, or lack thereof, will become increasingly sought after and supported. PMID- 26683510 TI - Big Data and the Future of Radiology Informatics. AB - Rapid growth in the amount of data that is electronically recorded as part of routine clinical operations has generated great interest in the use of Big Data methodologies to address clinical and research questions. These methods can efficiently analyze and deliver insights from high-volume, high-variety, and high growth rate datasets generated across the continuum of care, thereby forgoing the time, cost, and effort of more focused and controlled hypothesis-driven research. By virtue of an existing robust information technology infrastructure and years of archived digital data, radiology departments are particularly well positioned to take advantage of emerging Big Data techniques. In this review, we describe four areas in which Big Data is poised to have an immediate impact on radiology practice, research, and operations. In addition, we provide an overview of the Big Data adoption cycle and describe how academic radiology departments can promote Big Data development. PMID- 26683511 TI - Nocturnal Hypertension and Altered Night-Day BP Profile and Atherosclerosis in Renal Transplant Patients. AB - BACKGROUND: The clinical relevance of ambulatory blood pressure monitoring (ABPM) for risk stratification in renal transplant patients still remains poorly defined. METHODS: We investigated the association between clinic and ABPM with an established biomarker of atherosclerosis (intima-media thickness [IMT] by echo color Doppler) in a large, inclusive survey (n = 172) in renal transplant patients at a single institution. RESULTS: Forty-two patients (24%) were classified as hypertensive by ABPM criteria and 29 (17%) by clinic blood pressure (BP) criteria. Average daytime and nighttime BP was 126 +/- 12/78 +/- 9 mm Hg and 123 +/- 13/74 +/- 10 mm Hg, respectively. Forty-five patients (26%) were classified as hypertensive by the daytime criterion (>135/85 mm Hg) and a much higher proportion (n = 119, 69%) by the nighttime criterion (>120/70 mm Hg). Sixty-two patients (36%) had a night-day ratio of 1 or greater, indicating clear cut nondipping. The average nighttime systolic BP (r = 0.24, P = 0.001) and the night-day systolic BP ratio (r = 0.23, P = 0.002) were directly related to IMT, and these associations were much more robust than the 24-hour systolic BP-IMT relationship (r = 0.16, P = 0.04). Average daytime BP and clinic B were unrelated to IMT. In a multiple regression analysis adjusting for confounders, the night day systolic BP ratio maintained an independent association with IMT (beta = 0.14, P = 0.04). CONCLUSIONS: In renal transplant patients, the prevalence of nocturnal hypertension by far exceeds the prevalence of hypertension as assessed by clinic, daytime, and 24-hour ABPM. Nighttime systolic BP and the night-day ratio but no other BP metrics are independently associated with IMT. Blood pressure during nighttime may provide unique information for the assessment of cardiovascular risk attributable to BP burden in renal transplant patients. PMID- 26683512 TI - Acute Kidney Injury and Outcome After Heart Transplantation: Large Differences in Performance of Scoring Systems. AB - BACKGROUND: Kidney function is an important aspect for patient outcome after heart transplantation (HTX). Acute kidney injury (AKI) is defined by changes in serum creatinine (SCr) and diuresis with risk/injury/failure/loss/end stage (RIFLE), acute kidney injury network (AKIN), or kidney disease: improving global outcomes (KDIGO) scores. METHODS: We investigated the effect of perioperative AKI on 1-year mortality after HTX over a period of 10 years at a single-center university hospital. Multivariable Cox proportional-hazards regression analyzed the association between 1-year mortality and potential risk factors. Receiver operating curves for 1-year mortality were calculated to determine sensitivity and specificity of scores. RESULTS: Sixty of 346 patients (17%) died within the first year. Acute kidney injury was a predictor of mortality only in the high risk AKI groups of all scores: Hazard ratios (95% confidence interval) for RIFLE F: 7.164 (3.307-15.523); KDIGO/AKIN stage 3: 3.492 (2.006-6.081). Within each score, we identified patient groups, which had no elevated risk for an adverse outcome despite their allocation to the milder forms of AKI. In multivariable regression analysis, primary graft dysfunction was the predominant perioperative risk factor for 1-year mortality. CONCLUSIONS: In contrast to other patient cohorts, mild forms of perioperative AKI are of subordinate influence on patient outcome in HTX. PMID- 26683514 TI - A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. AB - BACKGROUND: Erythropoietin exerts anti-inflammatory, antiapoptotic, and cytoprotective effects in addition to its hematopoietic action. A nonhematopoietic erythropoietin analogue, ARA 290, has similar properties. The efficacy of pancreatic islet transplantation (PITx) is reduced due to islet damage that occurs during isolation and from the severe inflammatory reactions caused by the transplantation procedure. We investigated whether ARA 290 protects islets and ameliorates inflammatory responses following PITx thus improving engraftment. METHODS: The effects of ARA 290 on pancreatic islets of C57BL/6J (H 2) mice and on murine macrophages were investigated using an in vitro culture model. As a marginal PITx, 185 islets were transplanted into the liver of streptozotocin-induced diabetic mice (H-2) via the portal vein. Recipients were given ARA 290 (120 MUg/kg) intraperitoneally just before and at 0, 6, and 24 hours after PITx. Liver samples were obtained at 12 hours after PITx, and expression levels of proinflammatory cytokines were assessed. RESULTS: ARA 290 protected islets from cytokine-induced damage and apoptosis. Secretion of pro inflammatory cytokines (IL-6, IL-12, and TNF-alpha) from macrophages was significantly inhibited by ARA 290. After the marginal PITx, ARA 290 treatment significantly improved the blood glucose levels when compared to those of control animals (P < 0.001). Upregulation of monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta, IL-1beta, and IL-6 messenger RNA expression within the liver was suppressed by ARA 290 treatment. CONCLUSIONS: ARA 290 protected pancreatic islets from cytokine-induced damage and apoptosis and ameliorated the inflammatory response after PITx. ARA 290 appears to be a promising candidate for improvement of PITx. PMID- 26683513 TI - The Dichotomy of Endoplasmic Reticulum Stress Response in Liver Ischemia Reperfusion Injury. AB - Endoplasmic reticulum (ER) stress plays critical roles in the pathogenesis of liver ischemia-reperfusion injury (IRI). As ER stress triggers an adaptive cellular response, the question of what determines its functional outcome in liver IRI remains to be defined. In a murine liver partial warm ischemia model, we studied how transient (30 minutes) or prolonged (90 minutes) liver ischemia regulated local ER stress response and autophagy activities and their relationship with liver IRI. Effects of chemical chaperon 4-phenylbutyrate (4 PBA) or autophagy inhibitor 3-methyladenine (3-MA) were evaluated. Our results showed that although the activating transcription factor 6 branch of ER stress response was induced in livers by both types of ischemia, liver autophagy was activated by transient, but inhibited by prolonged, ischemia. Although 3-MA had no effects on liver IRI after prolonged ischemia, it significantly increased liver IRI after transient ischemia. The 4-PBA treatment protected livers from IRI after prolonged ischemia by restoring autophagy flux, and the adjunctive 3-MA treatment abrogated its liver protective effect. The same 4-PBA treatment, however, increased liver IRI and disrupted autophagy flux after transient ischemia. Although both types of ischemia activated 5' adenosine monophosphate activated protein kinase and inactivated protein kinase B (Akt), prolonged ischemia also resulted in downregulations of autophagy-related gene 3 and autophagy-related gene 5 in ischemic livers. These results indicate a functional dichotomy of ER stress response in liver IRI via its regulation of autophagy. Transient ischemia activates autophagy to protect livers from IRI, whereas prolonged ischemia inhibits autophagy to promote the development of liver IRI. PMID- 26683515 TI - Early Predictors of Long-term Outcomes of HCV-negative Liver Transplant Recipients Having Survived the First Postoperative Year. AB - BACKGROUND: The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV negative recipients. METHODS: This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections. RESULTS: Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P < 0.001), glomerular filtration rate (HR 0.89, P = 0.002), hypertension (HR 0.44, P < 0.001), early posttransplant infections (HR 1.52-1.67, P = 0.007 0.03), and alkaline phosphatase (ALP) (HR 1.05, P < 0.001). Elevated ALP at 1 year, affecting 30% of patients, predicted both graft loss and rejection, independent of immunologic stability, etiology, and immunosuppression type. Area under the curve of ALP in predicting graft loss from rejection was 0.81 (95% CI 0.71-0.90) and 0.85 (95% CI 0.72-0.98, P = 0.001) among patients under 50. Among immunologically stable patients who underwent transplantation after 2000, antimetabolite use at 1 year was associated with improved survival (P = 0.04), specifically in the subgroup with native-liver hepatocellular or biliary cancer (P = 0.02). CONCLUSIONS: Easily measurable, widely available, and noninvasive factors known at 1 year post-LT can help stratify patients according to their long-term risk of death or graft loss, and thus facilitate a personalization of long-term follow-up. ALP deserves routine monitoring, and the cause for an elevated ALP should be sought. PMID- 26683516 TI - Risk of Nephrectomy in Previous Living Kidney Donors. AB - BACKGROUND: For patients with a solitary kidney, such as living kidney donors, the surgical treatment of renal tumors may result in loss of function of the remaining kidney. METHODS: We conducted a retrospective, matched cohort study to determine the long-term risk of partial or total nephrectomy in previous living kidney donors compared to healthy nondonors. We reviewed the predonation charts for all living kidney donors in Ontario, Canada between 1992 and 2010 and linked this information to provincial healthcare databases. RESULTS: We matched 2119 donors to 21190 nondonors from the general population with similar baseline health. The median length of follow-up was 9.5 years (maximum 21.7 years). The rate of nephrectomy in follow-up was lower in donors versus nondonors (0 vs. 1.78 per 10000 person years; P = 0.037). In a subset of 1773 donors matched to 1773 healthy nondonors with renal imaging (median follow-up 7.6 years, maximum 21.0 years), the rate of nephrectomy was not statistically different in donors versus nondonors (0 vs. <=5 per 10000 person years; P > 0.08). CONCLUSION: No living kidney donor in our cohort received a partial or total nephrectomy of their remaining kidney during our follow-up period. Although we will continue to follow people in this study, these interim results are reassuring for the safety of kidney donation. PMID- 26683517 TI - Structure, Ionization, and Fragmentation of Neutral and Positively Charged Hydrogenated Carbon Clusters: C(n)H(m)(q+) (n = 1-5, m = 1-4, q = 0-3). AB - In this work we present a systematic theoretical study of neutral and positively charged hydrogenated carbon clusters (C(n)H(m)(q+) with n = 1-5, m = 1-4, and q = 0-3). A large number of isomers and spin states (1490 in total) was investigated. For all of them, we optimized the geometry and computed the vibrational frequencies at the B3LYP/6-311++G(3df,2dp) level of theory; more accurate values of the electronic energy were obtained at the CCSD(T)/6-311++G(3df,2dp) level over the geometry previously obtained. From these simulations we evaluated several properties such as relative energies between isomers, adiabatic and vertical ionization potentials, and dissociation energies of several fragmentation channels. A new analysis technique is proposed to evaluate a large number of fragmentation channels in a wide energy range. PMID- 26683518 TI - Designer Ionic Liquids for Reversible Electrochemical Deposition/Dissolution of Magnesium. AB - Chelating ionic liquids (ILs), in which polyether chains are pendent from the organic pyrrolidinium cation of the ILs (PEGylated ILs), were prepared that facilitate reversible electrochemical deposition/dissolution of Mg from a Mg(BH4)2 source. Mg electrodeposition processes in two specific PEGylated-ILs were compared against that in the widely studied N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ionic liquid (BMPyrTFSI). The two chelating IL systems (one with a pendent polyether chain with three ether oxygens, MPEG3PyrTFSI, and the other with a seven-ether chain, MPEG7PyrTFSI) showed substantial improvement over BMPyrTFSI for Mg electrodeposition/dissolution. The best overall electrochemical performance was in MPEG7PyrTFSI. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS) were used to characterize galvanostatically deposited Mg, revealing production of pure, dendrite-free Mg deposits. Reversible Mg electrodeposition was achieved with high Coulombic efficiency (CE) of 90% and high current density (ca. 2 mA/cm(2) for the stripping peak). Raman spectroscopy was used to characterize Mg(2+) speciation in the PEGylated ILs and BMPyrTFSI containing Mg(BH4)2 by study of Raman modes of the coordinated and free states of borohydride, TFSI(-), and polyether COC groups. Quantitative analysis revealed that the polyether chains can displace both TFSI(-) and BH4(-) from the coordination sphere of Mg(2+). Comparison of the different IL electrolytes suggested that these displacement reactions may play a role in enabling Mg deposition/dissolution with high CE and current density in these PEGylated IL media. These results represent the first demonstration of reversible electrochemical deposition/dissolution of Mg in an ionic liquid specifically designed with this task in mind. PMID- 26683519 TI - Metformin may reduce oral cancer risk in patients with type 2 diabetes. AB - BACKGROUND: Whether metformin use may affect the risk of oral cancer required further investigation. METHODS: The reimbursement database of the National Health Insurance in Taiwan was used. Patients with type 2 diabetes mellitus at an onset age of 25-74 years during 1999-2005 and newly treated with either metformin (n = 288198, "ever users of metformin") or other antidiabetic drugs (n = 16263, "never users of metformin") were followed for at least 6 months for oral cancer until December 31, 2011. The treatment effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression adjusted for propensity score (PS) or incorporated with the inverse probability of treatment weighting (IPTW) using PS. RESULTS: The respective numbers of incident oral cancer in ever users and never users were 1273 (0.44%) and 119 (0.73%), with respective incidences of 92.7 and 163.6 per 100,000 person years. The overall hazard ratios (95% confidence intervals) suggested a significantly lower risk [0.584 (0.483-0.707) for PS-adjusted model, and 0.562 (0.465-0.678) for IPTW model]. In tertile analyses, the PS-adjusted hazard ratios (95% confidence intervals) for the first (<21.5 months), second (21.5-45.9 months) and third (>45.9 months) tertile of cumulative duration were 1.403 (1.152 1.708), 0.557 (0.453-0.684) and 0.152 (0.119-0.194), respectively; and were 1.244 (1.024-1.511), 0.526 (0.429-0.645) and 0.138 (0.108-0.176), respectively, for IPTW. CONCLUSIONS: Metformin may significantly reduce the risk of oral cancer, especially when the cumulative duration is more than 21.5 months. PMID- 26683520 TI - Enhancement of adoptive T cell transfer with single low dose pretreatment of doxorubicin or paclitaxel in mice. AB - Ex vivo expansion of CD8+ T-cells has been a hindrance for the success of adoptive T cell transfer in clinic. Currently, preconditioning with chemotherapy is used to modulate the patient immunity before ACT, however, the tumor microenvironment beneficial for transferring T cells may also be damaged. Here preconditioning with single low dose of doxorubicin or paclitaxel combined with fewer CD8+ T-cells was investigated to verify whether the same therapeutic efficacy of ACT could be achieved. An E.G7/OT1 animal model that involved adoptive transfer of OVA-specific CD8+ T-cells transduced with a granzyme B promoter-driven firefly luciferase and tomato fluorescent fusion reporter gene was used to evaluate this strategy. The result showed that CD8+ T-cells were activated and sustained longer in mice pretreated with one low-dose Dox or Tax. Enhanced therapeutic efficacy was found in Dox or Tax combined with 2x106 CD8+ T cells and achieved the same level of tumor growth inhibition as that of 5x106 CD8+ T-cells group. Notably, reduced numbers of Tregs and myeloid derived suppressor cells were shown in combination groups. By contrast, the number of tumor-infiltrating cytotoxic T lymphocytes and IL-12 were increased. The NF kappaB activity and immunosuppressive factors such as TGF-beta, IDO, CCL2, VEGF, CCL22, COX-2 and IL-10 were suppressed. This study demonstrates that preconditioning with single low dose Dox or Tax and combined with two fifth of the original CD8+ T-cells could improve the tumor microenvironment via suppression of NF-kappaB and its related immunosuppressors, and activate more CD8+ T-cells which also stay longer. PMID- 26683521 TI - Cytokine secretion and NK cell activity in human ADAM17 deficiency. AB - Genetic deficiencies provide insights into gene function in humans. Here we describe a patient with a very rare genetic deficiency of ADAM17. We show that the patient's PBMCs had impaired cytokine secretion in response to LPS stimulation, correlating with the clinical picture of severe bacteremia from which the patient suffered. ADAM17 was shown to cleave CD16, a major NK killer receptor. Functional analysis of patient's NK cells demonstrated that his NK cells express normal levels of activating receptors and maintain high surface levels of CD16 following mAb stimulation. Activation of individual NK cell receptors showed that the patient's NK cells are more potent when activated directly by CD16, albeit no difference was observed in Antibody Depedent Cytotoxicity (ADCC) assays. Our data suggest that ADAM17 inhibitors currently considered for clinical use to boost CD16 activity should be cautiously applied, as they might have severe side effects resulting from impaired cytokine secretion. PMID- 26683523 TI - The use of portable ultrasound devices in low- and middle-income countries: a systematic review of the literature. AB - OBJECTIVES: To review the scientific literature pertaining to the use of hand carried and hand-held ultrasound devices in low- and middle-income countries (LMIC), with a focus on clinical applications, geographical areas of use, the impact on patient management and technical features of the devices used. METHODS: The electronic databases PubMed and Google Scholar were searched. No language or date restrictions were applied. Case reports and original research describing the use of hand-carried ultrasound devices in LMIC were included if agreed upon as relevant by two-reviewer consensus based on our predefined research questions. RESULTS: A total of 644 articles were found and screened, and 36 manuscripts were included for final review. Twenty-seven studies were original research articles, and nine were case reports. Several reports describe the successful diagnosis and management of difficult, often life-threatening conditions, using hand-carried and hand-held ultrasound. These portable ultrasound devices have also been studied for cardiac screening exams, as well as a rapid triage tool in rural areas and after natural disaster. Most applications focus on obstetrical and abdominal complaints. Portable ultrasound may have an impact on clinical management in up to 70% of all cases. However, no randomised controlled trials have evaluated the impact of ultrasound-guided diagnosis and treatment in resource-constrained settings. The exclusion of articles published in journals not listed in the large databases may have biased our results. Our findings are limited by the lack of higher quality evidence (e.g. controlled trials). CONCLUSIONS: Hand-carried and hand-held ultrasound is successfully being used to triage, diagnose and treat patients with a variety of complaints in LMIC. However, the quality of the current evidence is low. There is an urgent need to perform larger clinical trials assessing the impact of hand-carried ultrasound in LMIC. PMID- 26683522 TI - Oxidative stress induces the acquisition of cancer stem-like phenotype in breast cancer detectable by using a Sox2 regulatory region-2 (SRR2) reporter. AB - We have previously identified a novel intra-tumoral dichotomy in breast cancer based on the differential responsiveness to a Sox2 reporter (SRR2), with cells responsive to SRR2 (RR) being more stem-like than unresponsive cells (RU). Here, we report that RR cells derived from MCF7 and ZR751 displayed a higher tolerance to oxidative stress than their RU counterparts, supporting the concept that the RR phenotype correlates with cancer stemness. Sox2 is directly implicated in this differential H2O2 tolerance, since siRNA knockdown of Sox2 in RR cells leveled this difference. Interestingly, H2O2 converted a proportion of RU cells into RR cells, as evidenced by their expression of luciferase and GFP, markers of SRR2 activity. Compared to RU cells, converted RR cells showed a significant increase in mammosphere formation and tolerance to H2O2. Converted RR cells also adopted the biochemical features of RR cells, as evidenced by their substantial increase in Sox2-SRR2 binding and the expression of 3 signature genes of RR cells (CD133, GPR49 and MUC15). Lastly, the H2O2-induced RU/RR conversion was detectable in a SCID mouse xenograft model and primary tumor cells. To conclude, the H2O2-induced RU/RR conversion has provided a novel model to study the acquisition of cancer stemness and plasticity. PMID- 26683524 TI - Cascade Mn-Mediated gamma-Alkylation/oxa-Michael Addition of Enones with 1,3 Dicarbonyls. AB - A radical-based strategy for regioselective gamma-C-C bond formation/oxa conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3-dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by Mn(III) . The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well-tolerated and bond formation occurs readily to form neopentyl and all-carbon quaternary centers in good yields. Several stereo- and chemoselective transformations of the products are described. PMID- 26683525 TI - The clinical challenges of akathisia. AB - Akathisia is one of the most vexing problems in neuropsychiatry. Although it is one of the most common side effects of antipsychotic medications, it is often difficult to describe by patients, and is difficult to diagnose and treat by practitioners. Akathisia is usually grouped with extrapyramidal movement disorders (ie, movement disorders that originate outside the pyramidal or corticospinal tracts and generally involve the basal ganglia). Yet, it can present as a purely subjective clinical complaint, without overt movement abnormalities. It has been subtyped into acute, subacute, chronic, tardive, withdrawal-related, and "pseudo" forms, although the distinction between many of these is unclear. It is therefore not surprising that akathisia is generally either underdiagnosed or misdiagnosed, which is a serious problem because it can lead to such adverse outcomes as poor adherence to medications, exacerbation of psychiatric symptoms, and, in some cases, aggression, violence, and suicide. In this article, we will attempt to address some of the confusion surrounding the condition, its relationship to other disorders, and differential diagnosis, as well as treatment alternatives. PMID- 26683526 TI - Treating to target in major depressive disorder: response to remission to functional recovery. AB - Treating to target in chronic diseases [e.g. Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes. PMID- 26683527 TI - Cognitive impairment in schizophrenia: the great unmet need. AB - Cognitive impairment in schizophrenia is present in almost all persons with the disorder and can be a substantial obstacle to efforts in the recovery process. In clinical research, cognition is assessed through neuropsychological testing as well as by different types of structured instruments focusing on function. Although nonpharmacological interventions such as cognitive remediation have been therapeutic, particularly in combination with vocational rehabilitation and supported employment, these modalities are not always easy to access. Pharmacological interventions are in development and have principally focused on the dopamine, glutamate, and acetylcholine neurotransmitter systems, aiming to target the dorsolateral prefrontal cortex and its interactions with other brain regions. PMID- 26683528 TI - A primer on binge eating disorder diagnosis and management. AB - Binge eating disorder (BED) is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among U.S. adults, yet often goes unrecognized. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BED is defined by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. It can affect both men and women, regardless if they are at normal weight, overweight, or obese, and regardless of their ethnic or racial group. Psychiatric comorbidities are very common, with 79% of adults with BED also experiencing anxiety disorders, mood disorders, impulse control disorders, or substance use disorders; almost 50% of persons with BED have >= 3 psychiatric comorbidities. Multiple neurobiological explanations have been proffered for BED, including dysregulation in reward center and impulse control circuitry, with potentially related disturbances in dopamine neurotransmission and endogenous MU-opioid signaling. Additionally, there is interplay between genetic influences and environmental stressors. Psychological treatments such as cognitive behavioral interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED; however, at present, there is one approved agent for the treatment of moderate to severe BED-lisdexamfetamine, a stimulant that was originally approved for the treatment of attention deficit hyperactivity disorder. PMID- 26683529 TI - Wound Healing Society 2015 update on guidelines for pressure ulcers. PMID- 26683530 TI - 4D cone beam CT-based dose assessment for SBRT lung cancer treatment. AB - The purpose of this research is to develop a 4DCBCT-based dose assessment method for calculating actual delivered dose for patients with significant respiratory motion or anatomical changes during the course of SBRT. To address the limitation of 4DCT-based dose assessment, we propose to calculate the delivered dose using time-varying ('fluoroscopic') 3D patient images generated from a 4DCBCT-based motion model. The method includes four steps: (1) before each treatment, 4DCBCT data is acquired with the patient in treatment position, based on which a patient specific motion model is created using a principal components analysis algorithm. (2) During treatment, 2D time-varying kV projection images are continuously acquired, from which time-varying 'fluoroscopic' 3D images of the patient are reconstructed using the motion model. (3) Lateral truncation artifacts are corrected using planning 4DCT images. (4) The 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach is validated using six modified XCAT phantoms with lung tumors and different respiratory motions derived from patient data. The estimated doses are compared to that calculated using ground-truth XCAT phantoms. For each XCAT phantom, the calculated delivered tumor dose values generally follow the same trend as that of the ground truth and at most timepoints the difference is less than 5%. For the overall delivered dose, the normalized error of calculated 3D dose distribution is generally less than 3% and the tumor D95 error is less than 1.5%. XCAT phantom studies indicate the potential of the proposed method to accurately estimate 3D tumor dose distributions for SBRT lung treatment based on 4DCBCT imaging and motion modeling. Further research is necessary to investigate its performance for clinical patient data. PMID- 26683531 TI - That antibiotic prophylaxis should be used in children with repaired oesophageal atresia and or trachea-oesophageal fistula - The case in favour. PMID- 26683533 TI - Playing match venue does not affect resting salivary steroids in elite Futsal players. AB - This study examined the influence of competition playing venue on the hormonal responses in elite Futsal players. Twenty-one males (age, 19.3 +/- 0.7 years; height, 174.2 +/- 4.1cm; body mass, 71.8 +/- 7.9 kg) from two Futsal teams were monitored during two competitive matches that were played against each other on a home and away basis. Saliva sampling was conducted before (pre) and after (post) each match. The concentration of salivary steroids (testosterone [T] and cortisol [C]) was assessed by ELISA. Resting concentration of salivary steroid (T and C) hormones was not affected by playing venue (home and away). Both Futsal matches promoted a significant increase in T and C from pre--to post-matches (p<0.05), with a higher post-C concentration for playing at home (p<0.05). No effect of playing venue on T was observed. In conclusion, the findings of this study indicate that the playing venue did not elicit a significant change in resting concentration of salivary steroid hormones. However, playing home induced a greater post-match C response, suggesting that the pressure for positive results in front of supporters, families and friends may impose a higher level of stress on the players at their own facility. PMID- 26683532 TI - Qualitative development of the sinus control test: a survey evaluating sinus symptom control. AB - BACKGROUND: Ideal management of chronic rhinosinusitis (CRS) requires ongoing monitoring of disease and its control. Existing control instruments are limited in their correlation to patient reported outcomes, the need for endoscopy, or lack of validation from a multidisciplinary group. The goal of this study was to develop a patient-based Sinus Control Test (SCT) for determining CRS control. METHODS: A systematic literature review and focus groups consisting of 20 patients and 11 medical experts in CRS from various medical specialties were used to generate items. A draft 13-item questionnaire was administered to 50 patients with CRS in a prospective fashion. Patients were evaluated using the 22-item Sino Nasal Outcome Test (SNOT-22) instrument, Lund-Mackay computed tomography (CT) score, and Lund-Kennedy endoscopy score. A rhinologist blinded to the questionnaire results also provided an overall control of the disease for each patient. A regression model was generated to identify which subset of items showed the greatest discriminate ability in relation to specialist's and patient's global rating of disease control. RESULTS: Four questions were included in the final questionnaire (p < 0.05), each with a scale of 0 to 4, with an overall total score ranging from 0 to 16. Optimal classification resulted in patients with a score from 1 to 3 (well controlled), 4 to 11 (partially controlled), and 12 to 16 (uncontrolled). SCT scores correctly classified control levels 72% of the time when compared to physician's assessment. CONCLUSION: The SCT is a simple, patient generated questionnaire that can measure the control of CRS without requirement of endoscopy or CT evaluation. PMID- 26683534 TI - Water-resistant cellulosic filter for aerosol entrapment and water purification, Part I: production of water-resistant cellulosic filter. AB - Synthetic filters are neither biodegradable nor produced from renewable sources. Thus, their disposal has serious environmental impacts. There is a growing desire to produce filters from cellulosic fibers that are renewable, biodegradable, cheap and most importantly recyclable if the contamination is removed. Foam-laid process in papermaking is a promising process for the production of specialty papers. Filters produced using this process are capable of providing products with high specific surface area and tortuous structure favorable for entrapping particulate matters, while providing excellent permeability for incoming gas or liquid. Although the end product fulfills completely the requirement of a filter in a dry environment, it fails completely if it is exposed to a moist environment. This work reports on converting the hydrophilic cellulosic filter into a hydrophobic product without disturbing its original structure. PMID- 26683535 TI - The utility of tumor markers and neutrophil lymphocyte ratio in patients with an intraoperative diagnosis of mucinous borderline ovarian tumor. AB - OBJECTIVE: To evaluate the utility of tumor markers and complete blood count to increase the diagnostic accuracy to detect malignant cases that are intraoperatively reported as mucinous borderline ovarian tumors (BOT). STUDY DESIGN: Patients who underwent laparotomy at our gynecologic oncology clinic between 2007 and 2015 for evaluation of an adnexal mass with an intraoperative frozen section report of mucinous BOT were retrospectively analyzed. Patients were grouped according to the final pathological diagnoses (malignant, borderline and benign), and were compared in terms of tumor marker levels and complete blood count parameters. Significant parameters were evaluated together with frozen section results, and were assessed for diagnostic accuracy. RESULTS: A total of 63 patients were included in the study. Of these, 41 patients had borderline, 11 patients had benign, and 11 patients had malignant mucinous ovarian tumors. Patient age, menopausal status, hemoglobin, platelet and lymphocyte counts were similar among the groups (p>0.05). On the other hand, white blood cell, neutrophil counts and neutrophil/lymphocyte ratio (NLR) were significantly higher in malignant cases (p<0.05). Similarly, CA125 and CA19-9 were significantly higher in malignant group (p<0.05). When evaluated with the frozen section results, CA19-9 and NLR had the highest sensitivity to detect mucinous cancers (81 and 78 percent, respectively). CONCLUSIONS: In patients who have an intraoperative frozen section diagnosis of borderline mucinous ovarian tumors, CA19-9, NLR and CA125 were significant predictors of malignancy. In light of larger future studies, we believe that integrating these parameters into routine clinical practice may decrease the rate of under diagnosis. PMID- 26683536 TI - Impact of body mass index on treatment efficacy of mirabegron for overactive bladder in females. AB - OBJECTIVE: Conclusive data comparing treatment efficacy of OAB pharmacotherapy in normal weight versus obese patients are not available. Obesity represents a risk factor for OAB/LUTS. We hypothesized that the effect of treatment with mirabegron might be diminished in obese patients. STUDY DESIGN: One hundred sixty nine women were prescribed mirabegron, 50mg/day. Subjective and objective parameters were compared prior to and following three months of treatment. The study population was stratified into three groups according to a patients' BMI (A-normal weight, B overweight, C-obese). We compared the change in parameters before and after treatment within each group. Subsequently the differences between groups were correlated. The same analysis was performed separately in patients who failed anticholinergic therapy (n=85). A paired t-test was used to compare the parameters before and after the procedure within groups, and a two-sample t-test was applied to conduct a comparison between groups. A p value of <0.05 was considered statistically significant. RESULTS: Significant improvement (p<0.001) within all groups was observed in all parameters, with an exception in the number of severe urgency episodes per 24h (p=0.291) in Group B. We did not observe any statistically significant difference between groups A, B and C. The same trend has been observed in subgroup of patients, who did not respond previous antimuscarinic treatment. CONCLUSIONS: This study provides evidence in support of previously documented data indicating good efficacy of mirabegron in the treatment of OAB. The data obtained do not confirm our hypothesis that the body weight influences the treatment outcome of mirabegron. PMID- 26683537 TI - Comment on "A revealed preference approach to valuing non-market recreational fishing losses from the Deepwater Horizon Oil Spill" and its "Corrigendum" by Alvarez et al. AB - This Comment identifies and discusses several methodological errors in the application of choice modeling that appear in an article and Corrigendum by Alvarez et al. published in this journal. The purpose is to clarify the correct methods as an aid to future researchers. PMID- 26683538 TI - Reply to "Comment on: A revealed preference approach to valuing non-market recreational fishing losses from the deepwater horizon oil spill and its corrigendum". PMID- 26683539 TI - New insights into a complex fungal pathogen: the case of Paracoccidioides spp. AB - Paracoccidioidomycosis is a systemic mycosis endemic to Latin America, with Paracoccidioides brasiliensis and P. lutzii being the causal agents of this disorder. Several issues have been raised in the 100 years since its discovery and in this article we discuss features of this fascinating fungal pathogen, including its biology, eco-epidemiology and aspects of its pathogenicity. We also consider some of its virulence determinants, the most recent advances in the study of its metabolic pathways and the molecular and genetic research tools developed for this research. We also review the animal models used to study host fungal interactions and how the host defence mechanisms against this pathogen work. PMID- 26683540 TI - [Hemolytic uremic syndrome in young adult with metabolic disorder of cobalamin: A case report]. PMID- 26683541 TI - Vehicle choices for teenage drivers: A national survey of U.S. parents. AB - INTRODUCTION: Previous research has shown that many newly licensed teenagers in the United States are driving vehicles with inferior crash protection. The objective of this study was to update and extend previous research on U.S. parents' choices of vehicles for their teenagers. METHOD: Telephone surveys were conducted with parents in May 2014 using a random sample of U.S. households likely to include teenagers. Participation was restricted to parents or guardians of teenagers who lived in the household and held either an intermediate or full driver's license. Parents were interviewed about the vehicle their teenager drives, the reason they chose the vehicle for their teenager, and the cost of purchased vehicles. RESULTS: Teenagers most often were driving 2000-06 model year vehicles (41%), with 30% driving a more recent model year and 19% driving an older model year. Teenagers most often were driving midsize or large cars (27%), followed by SUVs (22%), mini or small cars (20%), and pickups (14%). Far fewer were driving minivans (6%) or sports cars (1%). Forty-three percent of the vehicles driven by teenagers were purchased when the teenager started driving or later. A large majority (83%) were used vehicles. The median cost of the vehicles purchased was $5300, and the mean purchase price was $9751. CONCLUSIONS: Although parents report that the majority of teenagers are driving midsize or larger vehicles, many of these vehicles likely do not have key safety features, such as electronic stability control, which would be especially beneficial for teenage drivers. Many teenagers were driving older model year vehicles or vehicle types or sizes that are not ideal for novice drivers. PRACTICAL APPLICATIONS: Parents, and their teenage drivers, may benefit from consumer information about optimal vehicle choices for teenagers. PMID- 26683542 TI - Determinants of seat belt use: A regression analysis with FARS data corrected for self-selection. AB - INTRODUCTION: We develop a methodology to use FARS data as an alternative to NOPUS in estimating seat belt usage. The advantages of using FARS over NOPUS are that (i) FARS is broader because it contains more variables relevant for policy analysis, (ii) FARS allows for easy multivariate regression analysis, and finally, (iii) FARS data is more cost-effective. METHODOLOGY: We apply a binary logit model in our analysis to determine the likelihood of seat belt usage given various occupant, vehicle, and built environment characteristics. Using FARS data, we derive coefficient estimates for categories such as vehicle occupants' age and night time seat belt use that observational surveys like NOPUS cannot easily provide. RESULTS: Our results indicate that policies should focus on passengers (as opposed to drivers), male and young vehicle occupants, and that law enforcement should focus on pick-up trucks, rural roads, and nights. We find evidence that primary seat belt laws are effective. CONCLUSIONS: Although this is primarily a methodological paper, we present and discuss our results in the context of public policy so that our findings are relevant for road safety practitioners, researchers, and policymakers. PMID- 26683543 TI - Participation in driver education/training courses during graduated driver licensing, and the effect of a time-discount on subsequent traffic offenses: Findings from the New Zealand Drivers Study. AB - INTRODUCTION: The New Zealand GDL includes a time-discount at the restricted license stage, for attendance at an approved driver education course. This is despite international evidence showing that earlier licensure associated with a time-discount can increase risk for newly licensed drivers. OBJECTIVE: To examine participation in driver education courses and especially those that qualify for a time-discount; compare the profiles of course participants with non-participants; examine reasons for participation; and examine the association between a time discount and traffic offenses once fully licensed. METHOD: This study was based on the New Zealand Drivers Study (NZDS), a prospective cohort study of newly licensed drivers. Data on driver education courses were obtained at the full license interview (n=1763), driver license and traffic offense data from the NZ Driver Licence Registry, and other data at the NZDS interviews. RESULTS: 94% had heard of and 49% (n=868) participated in a defensive driving course (DDC). No other course had more than 1% participation. Compared with the others, the DDC group were young, non-Maori, and from an area of relatively low deprivation. Through GDL, the DDC group were relatively more compliant with the conditions, and less likely to crash or receive a traffic offense notice. The groups did not differ on personality, alcohol and drug use. The reason most (85%) attended a DDC was to get their full license sooner; 86% (n=748) received a time-discount. The time-discount group were 40% more likely to receive a traffic offense notice on their full license; this reduced to 10% after controlling for other factors. CONCLUSION AND PRACTICAL IMPLICATIONS: The results of this study, when viewed in conjunction with other NZ crash evidence, indicate that a time-discount should not be given for completing a DDC or Street Talk course. PMID- 26683544 TI - Do as I say, not as I do: Distracted driving behavior of teens and their parents. AB - INTRODUCTION: Driver distraction is an important contributor to crash risk. Teenage driver distraction can be influenced by the attitudes and behaviors of parents. This study examined teens' and their parents' engagement in distracting behavior while driving. METHOD: Survey data were collected from a national sample of 403 parent-teen dyads using random-digit dialing telephone interviews. RESULTS: Results demonstrated few parent or teen sex differences in distracting behavior engagement while driving, or in their perceptions of each others' behavior. Parents and teens' frequencies of distracting behavior engagement were positively correlated. Parents' and teens' perceptions of each others' distracting behavior engagement while driving exceeded their own selfreports. Finally, the likelihood that teens reported engaging in distracting behavior while driving was more strongly associated with their perceptions of their parents' distracting behavior than by parents' self reports of their own behavior. CONCLUSIONS: These results suggest that parents' examples of driving behavior are an important influence on teen driving behavior, but potentially more important are teens' perceptions of their parents' behaviors. PMID- 26683545 TI - Intentions and knowledge shaping local safety policy: A comparison of two Swedish cities. AB - INTRODUCTION: This article explores how intentions and knowledge shape two Swedish cities' local safety policy (LSP). METHOD: The applied framework is derived from the integration of governance and implementation research and the theory of knowledge and its use. RESULTS: The study shows that LSPs are shaped by a mix of intentions and different kinds of knowledge, and intentions and knowledge interplay and intertwine in many ways. Key-persons construct LSPs when they work out solutions to urgent safety problems and take departure in the local context, its pre-conditions, and their experience-based and professional knowledge. The state governs LSP softly through management by objectives in the background, but more often key-actor intentions and commitments, local safety problems, and events initiated and influenced LSPs. CONCLUSIONS: The article contributes to a better understanding of conditions for LSPs in multi-level governance. PRACTICAL APPLICATIONS: The article can be used to improve governance, identify implementation problems and knowledge needs that will improve LSPs and the overall safety situation in the community. The study has implications for how LSPs should be evaluated; many different evaluation criteria can be appropriate, such as relevance, legitimacy, achievement of key actors' objectives, sustainability of policy solutions, and creation of a local safety culture. PMID- 26683546 TI - Effects of emphasis terminology in warning instructions on compliance intent and understandability. AB - INTRODUCTION: The aim of this study was to examine whether differing terminology in warning directives can influence compliance intentions and understandability. Despite its important role for warning effectiveness, warning instructions has not received much attention in warning research. Emphasis terms that can be used in warning directives were investigated. METHOD: Three experiments were conducted. In Experiment 1, participants rated a set of 12 warning directive statements consisted of one basic warning directive, which served as the control and the other 11 one- or two-word emphasis phrases that added to a basic directive. In Experiment 2, participants rated 37 emphasizers on compliance intent. In Experiment 3, participants rated the same emphasizers on understandability. RESULTS: The first 2 experiments showed substantial differences in compliance intentions depending on the emphasizer used. For example, some terms and phrases (e.g., "urgent") produced high compliance intent whereas others showed lower compliance intent (e.g., "recommended"). In Experiment 3, some terms were rated as understandable (e.g., "important"), whereas others were rated as somewhat understandable (e.g., "compulsory"). CONCLUSION: The addition of emphasis terms to the warning directives influenced people's compliance intent and understandability. In addition, significant correlations were found among compliance intent, understandability, and measures of variability. PRACTICAL APPLICATION: . The findings from this research could aid warning designers in selecting understandable wording that gives rise to different levels of compliance intentions. PMID- 26683547 TI - The direct cost burden of 13years of disabling workplace injuries in the U.S. (1998-2010): Findings from the Liberty Mutual Workplace Safety Index. AB - INTRODUCTION: Although occupational injuries are among the leading causes of death and disability around the world, the burden due to occupational injuries has historically been under-recognized, obscuring the need to address a major public health problem. METHODS: We established the Liberty Mutual Workplace Safety Index (LMWSI) to provide a reliable annual metric of the leading causes of the most serious workplace injuries in the United States based on direct workers compensation (WC) costs. RESULTS: More than $600 billion in direct WC costs were spent on the most disabling compensable non-fatal injuries and illnesses in the United States from 1998 to 2010. The burden in 2010 remained similar to the burden in 1998 in real terms. The categories of overexertion ($13.6B, 2010) and fall on same level ($8.6B, 2010) were consistently ranked 1st and 2nd. PRACTICAL APPLICATION: The LMWSI was created to establish the relative burdens of events leading to work-related injury so they could be better recognized and prioritized. Such a ranking might be used to develop research goals and interventions to reduce the burden of workplace injury in the United States. PMID- 26683548 TI - Behaving safely under pressure: The effects of job demands, resources, and safety climate on employee physical and psychosocial safety behavior. AB - INTRODUCTION: Previous research has shown that employees who experience high job demands are more inclined to show unsafe behaviors in the workplace. In this paper, we examine why some employees behave safely when faced with these demands while others do not. We add to the literature by incorporating both physical and psychosocial safety climate in the job demands and resources (JD-R) model and extending it to include physical and psychosocial variants of safety behavior. METHOD: Using a sample of 6230 health care employees nested within 52 organizations, we examined the relationship between job demands and (a) resources, (b) safety climate, and (c) safety behavior. We conducted multilevel analyses to test our hypotheses. RESULTS: Job demands (i.e., work pressure), job resources (i.e., job autonomy, supervisor support, and co-worker support) and safety climate (both physical and psychosocial safety climate) are directly associated with, respectively, lower and higher physical and psychosocial safety behavior. We also found some evidence that safety climate buffers the negative impact of job demands (i.e., work-family conflict and job insecurity) on safety behavior and strengthens the positive impact of job resources (i.e., co-worker support) on safety behavior. CONCLUSIONS: Regardless of whether the focus is physical or psychological safety, our results show that strengthening the safety climate within an organization can increase employees' safety behavior. Practical implication: An organization's safety climate is an optimal target of intervention to prevent and ameliorate negative physical and psychological health and safety outcomes, especially in times of uncertainty and change. PMID- 26683549 TI - If you've seen one construction worksite stretch and flex program ... you've seen one construction worksite stretch and flex program. AB - BACKGROUND: Work-related Musculoskeletal Disorders (WMSD) account for approximately one-third of all injuries in the U.S. construction industry. Many companies have implemented stretch and flex (s/f) programs to reduce WMSD despite a lack of evidence showing effectiveness. METHODS: We conducted a mixed-methods study to understand (a) why employers continue devoting resources to s/f programs; (b) how programs vary; and (c) any actual or perceived benefits. RESULTS: Nineteen safety and health professionals were interviewed and 133 more (13.3% response rate) completed an on-line survey. Fifty-six percent had implemented an s/f program with the primary goal of reducing WMSDs; though most did not review data to determine goal achievement. Program structure varied in terms of duration, frequency, and type of stretches. There was strong agreement about mandating attendance but not participation, due primarily to liability issues. Cost was a factor when deciding to implement a program but not for sustaining one. The majority had not implemented other ergonomic prevention activities, but many had started conducting daily safety huddles for task and safety planning. Those reporting a reduction in WMSDs agreed that it was not due to the s/f program alone and that other benefits included increased worker camaraderie, communication, and collaboration. CONCLUSION: Although there is little to no scientific evidence showing that they work as intended, construction companies continue to implement s/f programs with the goal of reducing WMSDs. Bringing work crews together for s/f activities has prompted employers to also begin conducting daily safety huddles. Although employers may not be able to link reduced WMDS to an s/f program, the ancillary benefits may warrant the time and resources. PRACTICAL APPLICATIONS: S/f programs should be only one component of a more comprehensive ergonomics prevention program. Conducting daily safety huddles at the same time also may enhance worker communication, camaraderie, collaboration and improve safety outcomes. PMID- 26683550 TI - Real-world effects of using a phone while driving on lateral and longitudinal control of vehicles. AB - INTRODUCTION: Technologies able to augment human communication, such as smartphones, are increasingly present during all daily activities. Their use while driving, in particular, is of great potential concern, because of the high risk that distraction poses during this activity. Current countermeasures to distraction from phone use are considerably different across countries and not always widely accepted/adopted by the drivers. METHODS: This study utilized naturalistic driving data collected from 108 drivers in the Integrated Vehicle Based Safety Systems (IVBSS) program in 2009 and 2010 to assess the extent to which using a phone changes lateral or longitudinal control of a vehicle. The IVBSS study included drivers from three age groups: 20-30 (younger), 40-50 (middle-aged), and 60-70 (older). RESULTS: Results from this study show that younger drivers are more likely to use a phone while driving than older and middle-aged drivers. Furthermore, younger drivers exhibited smaller safety margins while using a phone. Nevertheless, younger drivers did not experience more severe lateral/longitudinal threats than older and middle-aged drivers, probably because of faster reaction times. While manipulating the phone (i.e., dialing, texting), drivers exhibited larger lateral safety margins and experienced less severe lateral threats than while conversing on the phone. Finally, longitudinal threats were more critical soon after phone interaction, suggesting that drivers terminate phone interactions when driving becomes more demanding. CONCLUSIONS: These findings suggest that drivers are aware of the potential negative effect of phone use on their safety. This awareness guides their decision to engage/disengage in phone use and to increase safety margins (self-regulation). This compensatory behavior may be a natural countermeasure to distraction that is hard to measure in controlled studies. Practical Applications: Intelligent systems able to amplify this natural compensatory behavior may become a widely accepted/adopted countermeasure to the potential distraction from phone operation while driving. PMID- 26683551 TI - Exploring the factors affecting motorway accident severity in England using the generalised ordered logistic regression model. AB - PROBLEM: The severity of motorway accidents that occurred on the hard shoulder (HS) is higher than for the main carriageway (MC). This paper compares and contrasts the most important factors affecting the severity of HS and MC accidents on motorways in England. METHOD: Using police reported accident data, the accidents that occurred on motorways in England are grouped into two categories (i.e., HS and MC) according to the location. A generalized ordered logistic regression model is then applied to identify the factors affecting the severity of HS and MC accidents on motorways. The factors examined include accident and vehicle characteristics, traffic and environment conditions, as well as other behavioral factors. RESULTS: Results suggest that the factors positively affecting the severity include: number of vehicles involved in the accident, peak hour traffic time, and low visibility. Differences between HS and MC accidents are identified, with the most important being the involvement of heavy goods vehicles (HGVs) and driver fatigue, which are found to be more crucial in increasing the severity of HS accidents. PRACTICAL APPLICATIONS: Measures to increase awareness of HGV drivers regarding the risk of fatigue when driving on motorways, and especially the nearside lane, should be taken by the stakeholders. PMID- 26683552 TI - Assessing the number of fire fatalities in a defined population. AB - INTRODUCTION: Fire-related fatalities and injuries have become a growing governmental concern in Sweden, and a national vision zero strategy has been adopted stating that nobody should get killed or seriously injured from fires. There is considerable uncertainty, however, regarding the numbers of both deaths and injuries due to fires. Different national sources present different numbers, even on deaths, which obstructs reliable surveillance of the problem over time. We assume the situation is similar in other countries. This study seeks to assess the true number of fire-related deaths in Sweden by combining sources, and to verify the coverage of each individual source. By doing so, we also wish to demonstrate the possibilities of improved surveillance practices. METHOD: Data from three national sources were collected and matched; a special database on fatal fires held by The Swedish Contingencies Agency (nationally responsible for fire prevention), a database on forensic medical examinations held by the National Board of Forensic Medicine, and the cause of death register held by the Swedish National Board of Health and Welfare. RESULTS: The results disclose considerable underreporting in the single sources. The national database on fatal fires, serving as the principal source for policy making on fire prevention matters, underestimates the true situation by 20%. Its coverage of residential fires appears to be better than other fires. CONCLUSIONS: Systematic safety work and informed policy-making presuppose access to correct and reliable numbers. By combining several different sources, as suggested in this study, the national database on fatal fires is now considerably improved and includes regular matching with complementary sources. PMID- 26683553 TI - The effect of age and gender on motor vehicle driver injury severity at highway rail grade crossings in the United States. AB - INTRODUCTION: Based on the Federal Railway Administration (FRA) database, there were 25,945 highway-rail crossing accidents in the United States between 2002 and 2011. With an extensive database of highway-rail grade crossing accidents in the United States from 2002 to 2011, estimation results showed that there were substantial differences across age/gender groups for driver's injury severity. METHOD: The study applied an ordered probit model to explore the determinants of driver injury severity for motor vehicle drivers at highway-rail grade crossings. RESULTS: The analysis found that there are important behavioral and physical differences between male and female drivers given a highway-rail grade crossing accident happened. PRACTICAL APPLICATIONS: Older drivers have higher fatality probabilities when driving in open space under passive control especially during bad weather condition. Younger male drivers are found to be more likely to have severe injuries at rush hour with high vehicle speed passing unpaved highway-rail grade crossings under passive control. Synthesizing these results led to the conclusion that the primary problem with young is risk-taking and lack of vehicle handling skills. The strength of older drivers lies in their aversion to risk, but physical degradation issues which result in longer reaction/perception times and degradation in vision and hearing often counterbalance this attribute. PMID- 26683554 TI - Do industrial incidents in the chemical sector create equity market contagion? AB - INTRODUCTION: This paper examines a number of US chemical industry incidents and their effect on equity prices of the incident company. Furthermore, this paper then examines the contagion effect of this incident on direct competitors. METHOD: Event study methodology is used to assess the impact of chemical incidents on both incident and competitor companies. RESULTS: This paper finds that the incident company experiences deeper negative abnormal returns as the number of injuries and fatalities as a result of the incident increases. The equity value of the competitor companies suffer substantial losses stemming from contagion effects when disasters that occur cause ten or more injuries and fatalities, but benefit from the incident through increasing equity value when the level of injury and fatality is minor. CONCLUSIONS: Presence of contagion suggests collective action may reduce value destruction brought about by safety incidents that result in significant injury or loss of life. PRACTICAL APPLICATIONS: This research can be used as a resource to promote and justify the cost of safety mechanisms within the chemical industry, as incidents have been shown to negatively affect the equity value of the not just the incident company, but also their direct competitors. PMID- 26683555 TI - Smeed's law and expected road fatality reduction: An assessment of the Italian case. AB - INTRODUCTION: Smeed's law defines the functional relationship existing between the fatality rate and the motorization rate.While focusing on the Italian case and based on the Smeed's law, the study assesses the possibility for Italy of reaching the target of halving the number of road fatalities by 2020, in light of the evolving socioeconomic situation. METHOD: A Smeed's model has been calibrated based on the recorded Italian data. The evolution of the two indicators, fatality and motorization rates, has been estimated using the predictions of the main parameters (population, fleet size and fatalities). Those trends have been compared with the natural decreasing trend derived from the Smeed's law. RESULTS: Nine scenarios have been developed showing the relationship between the fatality rate and the motorization rate. In case of a limited increase (logistic regression) of the vehicle fleet and according to the estimated evolution of the population, the path defined by motorization and fatality rate is very steep, diverging from the estimated confidence interval of the Smeed's model. In these scenarios the motorization rate is almost constant during the decade. CONCLUSIONS: In the actual economic context, a limited development of the vehicle fleet is more plausible. In these conditions the target achievement of halving the number of fatalities in Italy may occur only in case of a structural break (i.e., the introduction of highly effective road safety policies). Practical application: The proposed tools can be used both to evaluate retrospectively the effectiveness of road safety improvements and to assess if a relevant effort is needed to reach the established road safety targets. PMID- 26683556 TI - Improving the safety effect of speed camera programs through innovations: Evidence from the French experience. AB - PROBLEM: This study investigates the effect of the French Automated Speed Enforcement Program (ASEP) on casualties involving different types of road users. METHOD: Interrupted time-series analyses were conducted to estimate the effect of the ASEP. RESULTS: Overall, the ASEP was associated with a decrease of 19.7% in traffic fatalities and crashes with injuries. Significant diminutions were observed for passenger vehicles/light SUVs (-25.4%), motorcyclists (-39.0%), and trucks (-15.7%). Adding red light cameras and devices taking pictures of both ends of the vehicle produced, in some cases, additional gains among specific categories of road users. CONCLUSION: Traffic fatalities, crashes with injuries and the severity of crashes significantly declined following the introduction of the ASEP in November 2003. Practical applications: ASEPs are an effective strategy to prevent traffic casualties. Innovations such as red light cameras and devices taking pictures of both ends of the vehicle can improve an ASEP. PMID- 26683557 TI - Assistive device use and mobility-related factors among adults aged>=65years. AB - INTRODUCTION: Examining how assistive device (cane, walker) use relates to other mobility factors can provide insight into older adults' future mobility needs. METHODS: Data come from the Second Injury Control and Risk Survey, Phase 2 (ICARIS2-P2), conducted from March 2007 to May 2008. Prevalence estimates were calculated for older adults (aged >=65) and multivariable logistic regression was used to explore associations between assistive device use and mobility-related characteristics. RESULT: Compared with non-users, assistive device users were more likely to report a recent fall (AOR 12.0; 95% CI 4.9-29.3), limit walking outside due to concerns about falling (AOR 7.1; 95% CI 2.6-19.1), be unable to walk outside for 10min without resting (AOR 3.3; 95% CI 1.1-9.3), and be no longer driving (AOR 6.7; 95% CI 2.0-22.3). CONCLUSION: Assistive device users have limited mobility and an increased risk for fall injury compared with non users. PRACTICAL APPLICATION: Effective fall prevention interventions, and innovative transportation options, are needed to protect the mobility of this high-risk group. PMID- 26683558 TI - Comprehension of safety pictograms affixed to agricultural machinery: A survey of users. AB - INTRODUCTION: Pictograms affixed to agricultural machinery are important tools to reduce the occurrence of accidents and injuries when correctly noticed, comprehended, and followed. This study investigated the knowledge of safety pictograms used in agricultural machinery in a sample of farmers and farm workers and examined the factors influencing their comprehension. METHOD: A questionnaire with 12 safety pictograms used for agricultural machinery was administered to 281 owners or users of agricultural machinery. For each of the pictograms, the participants had to select the most appropriate verbal description from among four choices. RESULTS: The pictograms examined yielded poor comprehension scores, including warnings related to the most frequent accidents involving agricultural machinery. Familiarity with the pictograms and years of experience with agricultural machinery significantly increased users' comprehension of the meaning of the pictograms. CONCLUSIONS: Specific training programs should be designed to draw attention to safety pictograms and to instill their meaning. PMID- 26683559 TI - Dropout during a driving simulator study: A survival analysis. AB - INTRODUCTION: Simulator sickness is the occurrence of motion-sickness like symptoms that can occur during use of simulators and virtual reality technologies. This study investigated individual factors that contributed to simulator sickness and dropout while using a desktop driving simulator. METHOD: Eighty-eight older adult drivers (mean age 72.82+/-5.42years) attempted a practice drive and two test drives. Participants also completed a battery of cognitive and visual assessments, provided information on their health and driving habits, and reported their experience of simulator sickness symptoms throughout the study. RESULTS: Fifty-two participants dropped out before completing the driving tasks. A time-dependent Cox Proportional Hazards model showed that female gender (HR=2.02), prior motion sickness history (HR=2.22), and Mini-SSQ score (HR=1.55) were associated with dropout. There were no differences between dropouts and completers on any of the cognitive abilities tests. CONCLUSIONS: Older adults are a high-risk group for simulator sickness. Within this group, female gender and prior motion sickness history are related to simulator dropout. Higher reported experience of symptoms of simulator sickness increased rates of dropout. PRACTICAL APPLICATIONS: The results highlight the importance of screening and monitoring of participants in driving simulation studies. Older adults, females, and those with a prior history of motion sickness may be especially at risk. PMID- 26683560 TI - Exploring factors contributing to crash injury severity on rural two-lane highways. AB - OBJECTIVE: Crash injury results from complex interaction among factors related to at-fault driver's behavior, vehicle characteristics, and road conditions. Identifying the significance of these factors which affect crash injury severity is critical for improving traffic safety. A method was developed to explore the relationship based on crash data collected on rural two-lane highways in China. METHODS: There were 673 crash records collected on rural two-lane highways in China. A partial proportional odds model was developed to examine factors influencing crash injury severity owing to its high ability to accommodate the ordered response nature of injury severity. An elasticity analysis was conducted to quantify the marginal effects of each contributing factor. RESULTS: The results show that nine explanatory variables, including at-fault driver's age, at fault driver having a license or not, alcohol usage, speeding, pedestrian involved, type of area, weather condition, pavement type, and collision type, significantly affect injury severity. In addition to alcohol usage and pedestrian involved, others violate the proportional odds assumption. At-fault driver's age of 25-39years, alcohol usage, speeding, pedestrian involved, pavement type of asphalt, and collision type of angle are found to be increased crash injury severity. PRACTICAL APPLICATIONS: The developed logit model has demonstrated itself efficient in identifying the effect of contributing factors on the crash injury severity. PMID- 26683561 TI - Applying human factors to develop an improved package design for (Rx) medication drug labels in a pharmacy setting. AB - As many as 98,000 people die every year from preventable medical errors. Among pharmacists, the most common error reported is the selection of the wrong drug. Merck met with the U.S. Food and Drug Administration (FDA) to discuss the optimization of the U.S. label for solid oral dosage forms of Merck medications. These discussions led to the development of revised label designs for six products that were then evaluated using failure modes and effects analysis and an expert review by human factors specialists. There were no errors among 425 filled prescriptions in the validation test of the final label. Key changes to the original labels include the use of a non-branded logo, high-contrast color bands for dosage strength, and an enhanced three-dimensional tablet image. The redesigned labels were approved by the US FDA in June 2011. PRACTICAL APPLICATIONS: The redesigned label should improve the accurate selection of medications from pharmacy shelves. PMID- 26683562 TI - The Driver Behaviour Questionnaire as accident predictor; A methodological re meta-analysis. AB - INTRODUCTION: The Manchester Driver Behaviour Questionnaire (DBQ) is the most commonly used self-report tool in traffic safety research and applied settings. It has been claimed that the violation factor of this instrument predicts accident involvement, which was supported by a previous meta-analysis. However, that analysis did not test for methodological effects, or include unpublished results. METHOD: The present study re-analysed studies on prediction of accident involvement from DBQ factors, including lapses, and many unpublished effects. Tests of various types of dissemination bias and common method variance were undertaken. RESULTS: Outlier analysis showed that some effects were probably not reliable data, but excluding them did not change the results. For correlations between violations and crashes, tendencies for published effects to be larger than unpublished ones and for effects to decrease over time were observed, but were not significant. Also, using the mean of accidents as proxy for effect indicated that studies where effects for violations are not reported have smaller effect sizes. These differences indicate dissemination bias. Studies using self reported accidents as dependent variables had much larger effects than those using recorded accident data. Also, zero-order correlations were larger than partial correlations controlled for exposure. Similarly, violations/accidents effects were strong only when there was also a strong correlation between accidents and exposure. Overall, the true effect is probably very close to zero (r<.07) for violations versus traffic accident involvement, depending upon which tendencies are controlled for. CONCLUSIONS: Methodological factors and dissemination bias have inflated the published effect sizes of the DBQ. Strong evidence of various artefactual effects is apparent. PRACTICAL APPLICATIONS: A greater level of care should be taken if the DBQ continues to be used in traffic safety research. Also, validation of self-reports should be more comprehensive in the future, taking into account the possibility of common method variance. PMID- 26683563 TI - A comprehensive examination of U.S. laws enacted to reduce alcohol-related crashes among underage drivers. AB - INTRODUCTION: To effectively address concerns associated with alcohol-related traffic laws, communities must apply comprehensive and well-coordinated interventions that account for as many factors as possible. The goal of the current research article is to examine and evaluate the simultaneous contribution of 20 underage drinking laws and 3 general driving safety laws, while accounting for demographic, economic, and environmental variables. METHODS: Annual fatal crash data (1982 to 2010), policies, and demographic, economic, and environmental information were collected and applied to each of the 51 jurisdictions (50 states and the District of Columbia). A structural equation model was fit to estimate the relative contribution of the variables of interest to alcohol-related crashes. RESULTS: As expected, economic factors (e.g., unemployment rate, cost of alcohol) and alcohol outlet density were found highly relevant to the amount of alcohol teens consume and therefore to teens' impaired driving. Policies such as those regulating the age of bartenders, sellers, or servers; social host civil liability laws; dram shop laws; internal possession of alcohol laws; and fake identification laws do not appear to have the same impact on teens' alcohol related crash ratios as other types of policies such as those regulating alcohol consumption or alcohol outlet density. CONCLUSIONS: This effort illustrates the need for comprehensive models of teens' impaired driving. After simultaneously accounting for as many factors as possible, we found that in general (for most communities) further reductions in alcohol-related crashes among teens might be more rapidly achieved from efforts focused on reducing teens' drinking rather than on reducing teens' driving. Future efforts should be made to develop models that represent specific communities. PRACTICAL APPLICATIONS: Based on this and community-specific models, simulation programs can be developed to help communities understand and visualize the impact of various policy alternatives. PMID- 26683564 TI - A draft fur seal genome provides insights into factors affecting SNP validation and how to mitigate them. AB - Custom genotyping arrays provide a flexible and accurate means of genotyping single nucleotide polymorphisms (SNPs) in a large number of individuals of essentially any organism. However, validation rates, defined as the proportion of putative SNPs that are verified to be polymorphic in a population, are often very low. A number of potential causes of assay failure have been identified, but none have been explored systematically. In particular, as SNPs are often developed from transcriptomes, parameters relating to the genomic context are rarely taken into account. Here, we assembled a draft Antarctic fur seal (Arctocephalus gazella) genome (assembly size: 2.41 Gb; scaffold/contig N50 : 3.1 Mb/27.5 kb). We then used this resource to map the probe sequences of 144 putative SNPs genotyped in 480 individuals. The number of probe-to-genome mappings and alignment length together explained almost a third of the variation in validation success, indicating that sequence uniqueness and proximity to intron-exon boundaries play an important role. The same pattern was found after mapping the probe sequences to the Walrus and Weddell seal genomes, suggesting that the genomes of species divergent by as much as 23 million years can hold information relevant to SNP validation outcomes. Additionally, reanalysis of genotyping data from seven previous studies found the same two variables to be significantly associated with SNP validation success across a variety of taxa. Finally, our study reveals considerable scope for validation rates to be improved, either by simply filtering for SNPs whose flanking sequences align uniquely and completely to a reference genome, or through predictive modelling. PMID- 26683565 TI - Unexpected positive and negative effects of continuing inbreeding in one of the world's most inbred wild animals. AB - Inbreeding depression, the reduced fitness of offspring of related individuals, is a central theme in evolutionary biology. Inbreeding effects are influenced by the genetic makeup of a population, which is driven by any history of genetic bottlenecks and genetic drift. The Chatham Island black robin represents a case of extreme inbreeding following two severe population bottlenecks. We tested whether inbreeding measured by a 20-year pedigree predicted variation in fitness among individuals, despite the high mean level of inbreeding and low genetic diversity in this species. We found that paternal and maternal inbreeding reduced fledgling survival and individual inbreeding reduced juvenile survival, indicating that inbreeding depression affects even this highly inbred population. Close inbreeding also reduced survival for fledglings with less-inbred mothers, but unexpectedly improved survival for fledglings with highly inbred mothers. This counterintuitive interaction could not be explained by various potentially confounding variables. We propose a genetic mechanism, whereby a highly inbred chick with a highly inbred parent inherits a "proven" genotype and thus experiences a fitness advantage, which could explain the interaction. The positive and negative effects we found emphasize that continuing inbreeding can have important effects on individual fitness, even in populations that are already highly inbred. PMID- 26683566 TI - Identification of a GJA3 Mutation in a Large Family with Bilateral Congenital Cataract. AB - The congenital cataract has been a clinically important cause of impaired vision development, making up about 10% of the cases of childhood blindness. Mutations of more than 40 genes have been identified causing congenital cataract with Mendelian inheritance, which indicated that it has an extremely high genetic heterogeneity. In this study, we recruited a large congenital cataract family and identified a missense mutation (c.143A>G: p.E48G) within gap junction protein alpha-3 (GJA3) gene in the proband using whole exome sequencing. Subsequent Sanger sequencing of this mutation in all family members revealed that this mutation cosegregated with the phenotype in the family with full penetrance. Our study identified a mutation in GJA3 that correlated with congenital cataract phenotype, which was not reported previously, and would be of benefit to the diagnosis of this genetic disorder. This finding expands the mutation spectrum of GJA3 and provides useful information for further study of the molecular pathogenesis of congenital cataract. PMID- 26683567 TI - Biotechnology for Chemical Production: Challenges and Opportunities. AB - Biotechnology offers a new sustainable approach to manufacturing chemicals, enabling the replacement of petroleum-based raw materials with renewable biobased feedstocks, thereby reducing greenhouse gas (GHG) emissions, toxic byproducts, and the safety risks associated with traditional petrochemical processing. Development of such bioprocesses is enabled by recent advances in genomics, molecular biology, and systems biology, and will continue to accelerate as access to these tools becomes faster and cheaper. PMID- 26683568 TI - The long-term outcome after treatment for patients with tibial fracture treated with intramedullary nailing is not influenced by time of day of surgery and surgeon experience. AB - INTRODUCTION: The objective of the present study was to evaluate the relationship between clinical outcome and time of day of surgery and experience level of the surgeon. Secondly, we examined the relationship between the length of hospital stay and the time of day of surgery. METHODS: This retrospective cross-sectional cohort design study included patients treated with intramedullary nailing at Aalborg University Hospital from 1998 to 2008 after tibial shaft fractures (N = 294). At follow-up, the participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS). Age, sex, complications, length of hospital stay, start time of surgery, and education level of surgeons were recorded. RESULTS: The long term analysis of the KOOS assessment shows no significant association between time of day of surgery and the level of surgeon experience. There was no difference in complication rates between time of day of surgery and the level of surgeon experience. The secondary outcome analysis showed an estimated increased risk of 25 % (p = 0.001), for a longer length of hospital stay when operated by a trainee at night-hours compared to day-hours, and an estimated increased risk of 17 % (p = 0.002) for longer length of stay, when operated at day-hours by a trauma surgeon compared to a trainee. CONCLUSION: Complication rates and KOOS outcome after surgery with intramedullary nailing were not influenced by time of day of surgery and experience level of the surgeon. The lengths of hospital stay increase significantly when surgery is performed at night by trainee surgeons, but not when performed by trauma surgeons. PMID- 26683569 TI - Chest Abdominal-Focused Assessment Sonography for Trauma during the primary survey in the Emergency Department: the CA-FAST protocol. AB - PURPOSE: To evaluate the feasibility of a new protocol, Chest Abdominal-Focused Assessment Sonography for Trauma (CA-FAST), during the primary survey and to estimate its diagnostic accuracy when compared with thoracoabdominal computed tomography (CT) scan. METHODS: A prospective accuracy study was performed from November 2012 to November 2013 at the Emergency Department. Only adult trauma patients who underwent a CA-FAST examination prior to a thoracoabdominal CT scan were enrolled. In addition to standard patterns detected by Extended-FAST (E FAST) such as pneumothorax (PTX), hemothorax (HTX), pericardial and intraabdominal effusion, CA-FAST protocol also included the research of lung contusions (LCs). RESULTS: Six hundred and one patients were enrolled. The mean time for protocol execution was 7 +/- 3 min. Chest ultrasonography showed the following results (all p < 0.001): LCs sensitivity 59 %, specificity 98 %, positive predictive value (PPV) 92 %, negative predictive value (NPV) 86 %, accuracy 87 %; PTX sensitivity 84 %, specificity 98 %, PPV 93 %, NPV 95 %, accuracy 95 %; HTX sensitivity 82 %, specificity 97 %, PPV 87 %, NPV 95 %, accuracy 94 %. The standard 4-views FAST examination showed a diagnostic accuracy of 91 % with a sensitivity of 75 %, specificity of 96 %, PPV of 81 % and NPV of 94 %. CONCLUSION: According to our results CA-FAST protocol proved to be a rapid bedside method, with good accuracy and high NPV in detection of ultrasonographic patterns suggestive of serious injury in trauma patients; moreover, the additional research of LCs did not cause a delay in the diagnosis. Ultrasonography should be used as initial investigation during the primary survey, sending to further diagnostic studies (CT scan) only those patients not clearly classified. PMID- 26683583 TI - Evolving technologies for growing, imaging and analyzing 3D root system architecture of crop plants. AB - A plant's ability to maintain or improve its yield under limiting conditions, such as nutrient deficiency or drought, can be strongly influenced by root system architecture (RSA), the three-dimensional distribution of the different root types in the soil. The ability to image, track and quantify these root system attributes in a dynamic fashion is a useful tool in assessing desirable genetic and physiological root traits. Recent advances in imaging technology and phenotyping software have resulted in substantive progress in describing and quantifying RSA. We have designed a hydroponic growth system which retains the three-dimensional RSA of the plant root system, while allowing for aeration, solution replenishment and the imposition of nutrient treatments, as well as high quality imaging of the root system. The simplicity and flexibility of the system allows for modifications tailored to the RSA of different crop species and improved throughput. This paper details the recent improvements and innovations in our root growth and imaging system which allows for greater image sensitivity (detection of fine roots and other root details), higher efficiency, and a broad array of growing conditions for plants that more closely mimic those found under field conditions. PMID- 26683585 TI - Impulsivity and Alcohol Dependence Treatment Completion: Is There a Neurocognitive Risk Factor at Treatment Entry? AB - BACKGROUND: Although there is considerable support for the relationship between impulsivity and alcohol dependence, little is known about the impact of neurocognitive aspects of impulsivity on treatment outcome. The aim of this study was to prospectively investigate the impact of neurocognitive impulsivity at treatment onset on treatment completion. METHODS: Forty-three alcohol-dependent patients entering inpatient treatment for alcohol dependence completed neurocognitive measures of impulsivity at the beginning of treatment. Assessments included prototypical measures of impulsive action (Go/No-go task [GNG] and Stop Signal Task [SST]) and impulsive choice (Delay Discounting Test [DDT], and Iowa Gambling Task). According to treatment outcomes, patients were divided into a patient group with regular treatment completion (e.g., with planned discharges, and without relapse during treatment) or irregular treatment course (e.g., premature and unplanned termination of treatment, "dropout," and/or relapse). RESULTS: Results show that, relative to patients completing treatment in a regular fashion (regular treatment completers [RTC]; 67%), those with an irregular course of treatment (relapse and/or dropout) (irregular treatment completers [ITC]; 33%) had significantly poorer GNG response inhibition performance (p = 0.011), and showed a trend toward greater delay discounting (DDT; p = 0.052) at treatment onset. Additional logistic regression analyses identified poor GNG response inhibition performance as a significant predictor for an irregular treatment course (GNG: p = 0.021; DDT: p = 0.067), particularly for relapse (GNG: p = 0.023). CONCLUSIONS: Neurocognitive impulsivity impacts upon treatment completion and appears sensitive for the prediction of relapse and dropout in alcohol-dependent patients. Poorer GNG response inhibition and a tendency toward steeper discounting of delayed rewards should be regarded as neurocognitive risk factors, which can be identified early in the course of alcohol dependence treatment. PMID- 26683586 TI - Metal Evaporation-Induced Degradation of Fullerene Acceptors in Polymer/Fullerene Solar Cells. AB - Surface-sensitive NEXAFS spectroscopy is used to probe the interaction between low work function metal electrodes and fullerene derivatives in organic solar cells. Evaporation of either Ca or Al electrodes onto films of the fullerene derivatives (6,6)-phenyl-C61-butyric acid methyl ester (PCBM) and indene-C60 bisadduct (ICBA) leads to a dramatic change in the observed NEXAFS spectrum. The observed changes cannot be explained only in terms of interfacial electronic doping or charge transfer, but rather point to the formation of new chemical bonds that destroy the extensive electron delocalization on the C60 cage. A combination of ex situ and in situ ultrahigh vacuum measurements indicates that metal evaporation results in a change in the electronic structure of PCBM that then facilitates chemical degradation and oxidation in the presence of oxygen. To investigate the effect of this chemical interaction on device performance, a unique transfer method to laminate the Al electrode to the top of polymer blend is used, in which case, the chemical degradation of the fullerene is not observed. Device performance of P3HT/PCBM blend solar cells in which the top metal electrode has either been thermally evaporated or transferred is then compared. These results highlight that chemical, as well as electronic, interactions between metals and organic semiconductors must be considered. PMID- 26683584 TI - CD14 is a key organizer of microglial responses to CNS infection and injury. AB - Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon beta mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced CNS responses to bacterial infection, traumatic and ischemic injuries, since CD14 deficiency causes either hypo- or hyperinflammation, insufficient or exaggerated immune cell recruitment or worsened stroke outcomes. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges. PMID- 26683588 TI - Late Glacial Demographic Expansion Motivates a Clock Overhaul for Population Genetics. AB - The molecular clock hypothesis is fundamental in evolutionary biology as by assuming constancy of the molecular rate it provides a timeframe for evolution. However, increasing evidence shows time dependence of inferred molecular rates with inflated values obtained using recent calibrations. As recent demographic calibrations are virtually non-existent in most species, older phylogenetic calibration points (>1 Ma) are commonly used, which overestimate demographic parameters. To obtain more reliable rates of molecular evolution for population studies, I propose the calibration of demographic transition (CDT) method, which uses the timing of climatic changes over the late glacial warming period to calibrate expansions in various species. Simulation approaches and empirical data sets from a diversity of species (from mollusk to humans) confirm that, when compared with other genealogy-based calibration methods, the CDT provides a robust and broadly applicable clock for population genetics. The resulting CDT rates of molecular evolution also confirm rate heterogeneity over time and among taxa. Comparisons of expansion dates with ecological evidence confirm the inaccuracy of phylogenetically derived divergence rates when dating population level events. The CDT method opens opportunities for addressing issues such as demographic responses to past climate change and the origin of rate heterogeneity related to taxa, genes, time, and genetic information content. PMID- 26683587 TI - High Prevalence of Metabolic Syndrome and Cardiovascular Disease Risk Among People with HIV on Stable ART in Southwestern Uganda. AB - The objectives of this study were to determine the epidemiology and correlates of cardiovascular disease (CVD) risk among Ugandans on first-line antiretroviral therapy (ART). We conducted a cross-sectional study at an HIV clinic in southwestern Uganda. We enrolled adult patients on non-nucleoside-based ART regimens for a minimum of 2 years. We collected anthropometric and clinical measurements, smoking history, and blood for fasting lipid profile and blood sugar (FBS). Outcomes of interest were (1) presence of metabolic syndrome (at least two of the following: FBS >100 mg/dL, blood pressure of >=130/85 mmHg, triglycerides >=150 mg/dL, HDL <40 mg/DL, or waist circumference >=94 cm in males or >=80 cm in females); and (2) a Framingham score correlating to >5% 10-year CVD risk. Of the 250 participants enrolled, metabolic syndrome was detected in 145/250 (58%) of participants (62% in females and 50% in males). Forty-three participants (17%) had a Framingham risk correlating to a 5% or greater risk for CVD within 10 years (26% in males and 13% in females). In multivariate analyses, being female (AOR 3.13; 95% CI: 1.0-9.70; p = 0.04) and over 40 years of age (AOR 1.78; 95% CI: 1.00-3.17; p = 0.05) was independently associated with having metabolic syndrome. We found no independent risk factors for a Framingham risk score 10-year risk exceeding 5%, or associations between ART regimen and CVD risk profiles. We conclude that metabolic abnormalities are common among patients on first-line ART in rural Uganda, and appear to be more common in women than men. PMID- 26683589 TI - Children of chronically ill parents: Relationship between parental multiple sclerosis and childhood developmental health. AB - BACKGROUND: Exposure to parental chronic illness is associated with adverse developmental outcomes. OBJECTIVE: We examined the association between parental multiple sclerosis (MS) and parental MS-related clinical factors on developmental health. METHODS: We conducted a population-based cohort study in British Columbia, Canada, using linked health databases. The outcome was childhood development at 5 years of age, expressed as vulnerability on the Early Development Instrument (EDI). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. RESULTS: MS affected parents (n = 783) were older, more likely to be English speakers, and had higher rates of mental health morbidity (39.6% vs 22.2%, p < 0.001) than unaffected parents (n = 2988). In the adjusted models, children of mothers with MS (aOR = 0.62, 95% CI = 0.44-0.87), but not children of the fathers with MS, had a lower risk of vulnerability on the social development domain of the EDI. However, mental health comorbidity (aOR = 1.62, 95% CI = 1.05-2.50) and physical comorbidity (aOR = 1.67, 95% CI = 1.05-2.64) among mothers with MS were associated with increased vulnerability on the EDI. CONCLUSION: Maternal MS, but not paternal MS, was associated with lower rates of developmental vulnerability on the social development domain. However, mental and physical comorbidity among MS-affected mothers were associated with increased developmental vulnerability in children. PMID- 26683590 TI - Longitudinal fMRI studies: Exploring brain plasticity and repair in MS. AB - Functional magnetic resonance imaging (fMRI) has greatly advanced our understanding of cerebral functional changes occurring in patients with multiple sclerosis (MS). However, most of our knowledge regarding brain plasticity and repair in MS as evidenced by fMRI has been extrapolated from cross-sectional studies across different phenotypes of the disease. This topical review provides an overview of this research, but also highlights limitations of existing fMRI studies with cross-sectional design. We then review the few existing longitudinal fMRI studies and discuss the feasibility and constraints of serial fMRI in individuals with MS. We further emphasize the potential to track fMRI changes in evolving disease and the insights this may give in terms of mechanisms of adaptation and repair, focusing on serial fMRI to monitor response to disease modifying therapies or rehabilitation interventions. Finally, we offer recommendations for designing future research studies to overcome previous methodological shortcomings. PMID- 26683591 TI - Measuring Current Drug Use in Female Sex Workers and Their Noncommercial Male Partners in Mexico: Concordance Between Data Collected From Surveys Versus Semi Structured Interviews. AB - BACKGROUND: Self-reports are commonly used to assess prevalence and frequency of drug use, but it is unclear whether qualitative methods like semi-structured interviews are as useful at obtaining such information as quantitative surveys. OBJECTIVES: This study compared drug use occurrence and frequency using data collected from quantitative surveys and qualitative interviews. We also examined whether combining data from both sources could result in significant increases in percentages of current users and whether the concordance between the two sets of data was associated with the type of drug use, age, gender and socioeconomic status. METHODS: Self- reports of recent marijuana, heroin, crack, cocaine, crystal/methamphetamine, inhalant, and tranquilizer use were collected using both methods from a cohort of Mexican female sex workers and their non-commercial male partners (n = 82). RESULTS: Participants were significantly less likely to report marijuana, cocaine and tranquilizer use and frequency of use during the qualitative interviews than during the quantitative surveys. Agreement on frequency of drug use was excellent for crystal/methamphetamine, heroin and inhalant use, and weak for cocaine, tranquilizers and marijuana use. Older participants exhibited significantly higher concordance than younger participants in reports of marijuana and methamphetamine use. Higher monthly income was significantly associated with higher concordance in crack use but lower concordance with marijuana use. CONCLUSIONS: Although use of such data can result in an underreporting of drug use, qualitative data can be quantified in certain circumstances to triangulate and confirm the results from quantitative analyses and provide a more comprehensive view of drug use. PMID- 26683592 TI - Liver transcriptome sequencing and de novo annotation of the large yellow croaker (Larimichthy crocea) under heat and cold stress. AB - Large yellow croaker is an economically important marine fish in China. To understand the molecular mechanisms of this fish under temperature stress, liver transcriptomes of large yellow croakers undergoing heat and cold stress were investigated. The results showed that 130,246 contigs from cold stressed fish (CS), 109,203 contigs from control fish (NS) and 98,569 contigs from heat stressed fish (HS) were obtained from the liver transcriptomes with de novo analysis, respectively. And in total, 9467 (6113 up-regulated and 3364 down regulated), 5350 (2185 up-regulated and 3165 down-regulated), 10,622 (3146 up regulated and 7477 down-regulated) significantly differentially expressed genes were identified in CS-NS, HS-NS, and HS-CS, respectively. Pathway enrichment analysis showed that many pathways including those of energy metabolism and metabolic pathways were affected after temperature stress. Further qPCR analysis also confirmed that the expression levels of genes coding for key enzymes in metabolic pathways were dramatically changed. PMID- 26683593 TI - Ginsenoside Represses Symptomatic Intracerebral Hemorrhage after Recombinant Tissue Plasminogen Activator Therapy by Promoting Transforming Growth Factor beta1. AB - BACKGROUND: Currently, the most effective treatment for brain ischemic stroke is recombinant tissue plasminogen activator (rt-PA); however, increased incidence of symptomatic intracerebral hemorrhage severely reduced its favorable treatment outcome. METHODS: We aimed to investigate the effect of ginsenoside (Gs) on symptomatic intracerebral hemorrhage after rt-PA treatment. Stroke patients were randomly divided into 2 treatment groups, one receiving rt-PA + placebo (Pc) and the other rt-PA + Gs. Twenty-four hours after the treatment, outcomes were assessed with transcranial Doppler (TCD) ultrasonography and National Institutes of Health Stroke Scale (NIHSS), and plasma levels of transforming growth factor beta1 (TGF-beta1), matrix metalloproteinase (MMP)-2, and MMP-9 were also measured. After initial cotreatment, the patients were continuously administered with either Pc or Gs, and the treatment outcomes at 7 days were assessed with TCD, NIHSS, modified Rankin scale (MRS), and Glasgow outcome scale (GOS). RESULTS: Cotreatment of rt-PA with Gs significantly improved outcomes in patients compared to the Pc group, as indicated by improved TCD and NIHSS scores and reduced incidence of symptomatic intracerebral hemorrhage, which could be attributed to a Gs-induced increase in TGF-beta1 and a decrease in both MMP-2 and MMP-9 serum levels. Seven days of Gs treatment also significantly improved outcomes in patients compared to the Pc group, assessed by TCD, NIHSS, MRS, and GOS. CONCLUSION: Our study supports the clinical use of Gs as a potential supplement with rt-PA treatment, which reduces symptomatic intracerebral hemorrhage, therefore improving the treatment outcome of stroke patients. PMID- 26683594 TI - Clinical Features and Related Factors of Poststroke Pathological Laughing and Crying: A Case-Control Study. AB - OBJECTIVES: The purpose of this study was to analyze clinical features and related factors of poststroke pathological laughing and crying (PSPLC) and to differentiate PSPLC patients with and without pseudobulbar signs. METHODS: We performed a case-control study in which 56 patients with PSPLC were matched to 56 control stroke patients by age and gender. The pathological laughing and crying scale was used to identify patients with PSPLC. Characteristics of PSPLC outbursts, presence of pseudobulbar signs and autonomic symptoms, lesion locations, and different clinical data were analyzed. Mild cognitive impairment (MCI) was evaluated by the Montreal Cognitive Assessment. Poststroke anger proneness (PSAP) was evaluated by comparison of the patients' premorbid states. RESULTS: Significantly more patients in the PSPLC group showed MCI, PSAP, and pseudobulbar signs than those in the control group. Most patients with PSPLC showed bilateral multiple lesions and the pons (especially the bilateral paramedian basal and basal-tegmental areas) stood out as the most important lesion location. Logistic regression analysis showed that pontine lesion, MCI, and PSAP were independently related to PSPLC; however, the presence of pseudobulbar signs was not related. PSPLC patients with pseudobulbar signs showed more recurrent strokes in the previous 2 years, more severe neurological deficits, as well as higher severity of PSPLC. In addition, more patients in the group with pseudobulbar signs showed concomitant autonomic symptoms. CONCLUSIONS: PSPLC, MCI, and PSAP could be manifestations of a more general disorder, in which pontine lesion plays an important role. PSPLC patients with pseudobulbar signs and those without show different features. PMID- 26683595 TI - Aspartate beta-hydroxylase modulates cellular senescence through glycogen synthase kinase 3beta in hepatocellular carcinoma. AB - Aspartate beta-hydroxylase (ASPH) is an enzyme overexpressed in human hepatocellular carcinoma (HCC) tumors that participates in the malignant transformation process. We determined if ASPH was a therapeutic target by exerting effects on cellular senescence to retard HCC progression. ASPH knockdown or knockout was achieved by short hairpin RNAs or the CRISPR/Cas9 system, respectively, whereas enzymatic inhibition was rendered by a potent second generation small molecule inhibitor of ASPH. Alterations of cell proliferation, colony formation, and cellular senescence were evaluated in human HCC cell lines. The potential mechanisms for activating cellular senescence were explored using murine subcutaneous and orthotopic xenograft models. Inhibition of ASPH expression and enzymatic activity significantly reduced cell proliferation and colony formation but induced tumor cell senescence. Following inhibition of ASPH activity, phosphorylation of glycogen synthase kinase 3beta and p16 expression were increased to promote senescence, whereas cyclin D1 and proliferating cell nuclear antigen were decreased to reduce cell proliferation. The mechanisms involved demonstrate that ASPH binds to glycogen synthase kinase 3beta and inhibits its subsequent interactions with protein kinase B and p38 upstream kinases as shown by coimmunoprecipitation. In vivo experiments demonstrated that small molecule inhibitor treatment of HCC bearing mice resulted in significant dose-dependent reduced tumor growth, induced phosphorylation of glycogen synthase kinase 3beta, enhanced p16 expression in tumor cells, and promoted cellular senescence. CONCLUSIONS: We have identified a new mechanism that promotes HCC growth and progression by modulating senescence of tumor cells; these findings suggest that ASPH enzymatic activity is a novel therapeutic target for HCC. PMID- 26683600 TI - SMFM 2016 Pregnancy Meeting: Looking Ahead to the Scientific Program (Podcast). PMID- 26683597 TI - Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions. AB - Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have roles in MS pathophysiology. We investigated CgA and CLU expression in lesions and nonlesional regions in postmortem brains of MS patients and controls and in the brains of marmosets with experimental autoimmune encephalomyelitis. By quantitative PCR, mRNA levels of CgA and CLU were elevated in white matter but not in grey matter of MS patients. In situ analyses showed greater expression of CgA and CLU in white matter lesions than in normal-appearing regions in MS patients and in the marmosets, primarily in or adjacent to perivascular spaces and inflammatory infiltrates. Both proteins were expressed by glial fibrillary acidic protein-positive astrocytes. CgA was more localized in astrocytic processes and endfeet surrounding blood vessels and was abundant in the superficial glia limitans and ependyma, 2 CSF-brain borders. Increased expression of CgA and CLU in reactive astrocytes in MS white matter lesions supports a role for these molecules as neuro-inflammatory mediators and their potential as CSF markers of active pathological processes in MS patients. PMID- 26683599 TI - The lung impedance monitoring in treatment of chronic heart failure (the LIMIT CHF study). AB - AIMS: To assess the usefulness of intrathoracic impedance monitoring (IIM) alerts in guiding empirical treatment of chronic heart failure (CHF) patients to prevent heart failure (HF) hospitalizations and unplanned HF care. METHODS AND RESULTS: Chronic heart failure patients with OptiVol or CorVue capable implantable cardioverter-defibrillators were randomized to either the active group (IIM alarm turned on and diuretic dose increased by 50% for 1 week in the event of alarm sounding) or the control group (IIM alarm turned off). The primary endpoint was the number of HF hospitalizations per patient at 1 year. The NYHA class, 6MWT, B type natriuretic peptide (BNP), and MLWHF questionnaire score were collected at baseline and follow-up. Eighty patients were included and 71 reached 1-year follow-up. There were 1.7 +/- 1.5 alerts in the active group and 1.1 +/- 1.0 in the control group, P = 0.07. In the active group, 61% of alerts led to a diuretic dose increase. There was a total of 11 HF hospitalizations in the active group vs. 6 in the control group without significant differences in the number of episodes per patient (0.3 +/- 0.9 vs. 0.2 +/- 0.4, P = 0.95). There were no unplanned HF visits in the active group vs. 0.1 +/- 0.3 per patient in the control group, P = 0.08. The total MLWHF scores were significantly increased at the final follow-up in the control group, whereas a trend towards reduction was observed in the active group. CONCLUSION: In this study, an empirical HF treatment guided by IIM alerts did not reduce emergency treatment of HF. However, it seems to have a positive impact on quality of life. CLINICAL TRIAL REGISTRATIONURL: http://www.clinicaltrials.gov. Unique identifier: NCT01320007. PMID- 26683601 TI - Predictive Capabilities of Neurobehavioral Diagnostics in Early Childhood. AB - Modern world experiences annual increase in the number of children born with neurological problems, which in the future may stipulate the development of their neurobehavioral and neuropsychological aberrations. Specific functional features of a child's brain development depend on many factors, but there is a strong need for early clinical and psychological identification of a child's development with a view to elaborate preventive measures, which are often more effective than the treatment or correction of dysfunction, already complicated by compensatory bonds. One should note that despite a high interest in the possibility of predicting the future development of the child in the early ontogenesis, few studies have so far been devoted to the search for indicators that could be meaningful for neuropsychology, neurology, and educational, special, and clinical psychology. PMID- 26683602 TI - Association of C609T-Inborn Polymorphism of NAD(P)H: Quinone Oxidoreductase 1 with the Risk of Bronchopulmonary Dysplasia in Preterm Neonates. AB - Objectives In bronchopulmonary dysplasia (BPD), direct exposure to oxygen therapy can damage the pulmonary epithelium via oxidative stress. The NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme detoxifies genotoxic products of oxidative stress. The corresponding gene is subject to an inactivating single-nucleotide polymorphism (C(609)T), which reduces detoxifying ability. The aim of this study was to investigate whether the C(609)T NQO1 inborn gene polymorphism is associated with an increased risk of BPD. Study Design Peripheral blood samples from 119 premature neonates <= 32 weeks of gestational age (42 BPD and 77 non BPD) were used for DNA extraction. NQO1 genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Results A significantly higher frequency of the NQO1 polymorphism was observed in BPD neonates compared with neonates without BPD. All neonates with <= 1,000 g birth weight who carried the mutant allele in heterozygous or homozygous state developed BPD. None of the BPD nonaffected group neonates with <= 1,000 g birth weight carried the NQO1 polymorphism. Conclusion The higher incidence of NQO1 mutants among BPD neonates as well as the presence of the mutant allele in all neonates with <= 1,000 g who developed BPD provided the first evidence for a possible pathogenetic role of the C(609)T polymorphism in BPD susceptibility due to the reduction or loss of NQO1 enzymatic activity. PMID- 26683603 TI - Antibiotic Stewardship Challenges in a Referral Neonatal Intensive Care Unit. AB - BACKGROUND: Antibiotic overuse in neonates is associated with adverse outcomes. Data are limited to guide antibiotic stewardship in the neonatal intensive care unit (NICU). Our objective was to identify areas for antibiotic stewardship improvement in a referral NICU. METHODS: Retrospective review of antibiotic use administered to infants admitted to a referral NICU compared with an inborn NICU. Antibiotic use was quantified by days of therapy (DOT) per 1,000 patient-days (PD). RESULTS: A total of 78% of referral NICU infants received >= 1 course of antibiotics. Infants in the referral NICU received more antibiotic DOT/1,000 PD than in the inborn NICU (558.9 vs. 343.2, p < 0.001), with a higher proportion of broad-spectrum therapy. For infants in the referral NICU, 39% of antibiotic courses were started at the transferring hospital; these were broader in spectrum (28 vs. 20%, p < 0.001) and less likely to be de-escalated or discontinued at 48 to 72 hours (58 vs. 87%, p < 0.001) than courses started after transfer. CONCLUSIONS: Compared with the inborn NICU, suspected sepsis in the referral NICU accounted for more antibiotic utilization, which was broad-spectrum and less likely to be de-escalated. Stewardship interventions should include reserving broad-spectrum therapy for infants with risk factors and de-escalating promptly once culture results become available. PMID- 26683604 TI - Efficiency of Screening for the Recurrence of Antenatal Group B Streptococcus Colonization in a Subsequent Pregnancy: A Systematic Review and Meta-analysis with Independent Patient Data. AB - OBJECTIVE: The objective of this study was to evaluate the risk of recurrent group B streptococcus (GBS) colonization in a subsequent pregnancy and to assess clinical characteristics that influence this risk. STUDY DESIGN: A systematic review and meta-analysis was performed. Databases were searched from inception through June 2015 using PubMed, Embase, Scopus, Central, and ClinicalTrials.gov. Studies were eligible if they assessed antenatal GBS colonization in two successive pregnancies. The quality of included studies was evaluated. Independent patient data was requested from the authors of the included trials. Unadjusted odds ratios (OR) were pooled using the Mantel-Haenszel fixed effect model. RESULTS: In the five studies identified, two studies lacked a nonexposed cohort. GBS colonization in the index pregnancy was associated with a higher risk of recurrence of GBS colonization in a subsequent pregnancy (three studies: 50.2 compared with 14.1%; pooled fixed effects OR, 6.05; 95% confidence interval [CI], 4.84-7.55). When heavy colonization with GBS was compared with colonization by vaginal culture only, an increased risk of recurrence was shown (four studies: 52.0 compared with 45.1%, pooled fixed effects OR, 1.54; 95% CI, 1.02-2.31). CONCLUSION: Women colonized with GBS are at significantly higher odds for recurrent colonization in a subsequent pregnancy when compared with women who were not colonized in an index pregnancy. If the individual is considered heavily colonized with GBS, there appears to be an association with an increased risk compared with conventional culture. Subgroup analysis of the variables time interval <= 12 months between subsequent pregnancies, body mass index >= 30 kg/m(2), race, ethnicity, and primiparous in the subsequent pregnancy showed no effect. PMID- 26683605 TI - Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis. AB - BACKGROUND: Pregnancy induces drastic biological changes systemically, and has a beneficial effect on some autoimmune conditions such as rheumatoid arthritis (RA). However, specific systemic changes that occur as a result of pregnancy have not been thoroughly examined in healthy women or women with RA. The goal of this study was to identify genes with expression patterns associated with pregnancy, compared to pre-pregnancy as baseline and determine whether those associations are modified by presence of RA. RESULTS: In our RNA sequencing (RNA-seq) dataset from 5 healthy women and 20 women with RA, normalized expression levels of 4,710 genes were significantly associated with pregnancy status (pre-pregnancy, first, second and third trimesters) over time, irrespective of presence of RA (False Discovery Rate (FDR)-adjusted p value<0.05). These genes were enriched in pathways spanning multiple systems, as would be expected during pregnancy. A subset of these genes (n = 256) showed greater than two-fold change in expression during pregnancy compared to baseline levels, with distinct temporal trends through pregnancy. Another 98 genes involved in various biological processes including immune regulation exhibited expression patterns that were differentially associated with pregnancy in the presence or absence of RA. CONCLUSIONS: Our findings support the hypothesis that the maternal immune system plays an active role during pregnancy, and also provide insight into other systemic changes that occur in the maternal transcriptome during pregnancy compared to the pre-pregnancy state. Only a small proportion of genes modulated by pregnancy were influenced by presence of RA in our data. PMID- 26683606 TI - Recombinant Reg3alpha protein protects against experimental acute pancreatitis in mice. AB - Regenerating gene 3alpha (Reg3alpha) protein is a trophic factor that stimulates cell and tissue proliferation, neogenesis and also acts against apoptosis and necrosis. In order to explore the potential roles of recombinant Reg3alpha (rReg3alpha), we produced a mature rReg3alpha polypeptide for direct administration in l-arginine (L-Arg) induced acute pancreatitis (AP) in mice. Our results showed that rReg3alpha stimulated cell proliferation through Erk1/2 and p38 phosphorylation and also cyclin D1 upregulation mediated by Akt/ATF-2 signaling. Moreover, rReg3alpha administration significantly reduced the pancreatic damage caused by L-Arg injection, as shown in histological examination and serum amylase, lipase and C-reactive protein (CRP) assays. Not only acinar cell necrosis but also apoptosis found in the pancreas of AP mice were alleviated by rReg3alpha. Finally, upregulated Bcl-2 and Bcl-xL and suppressed poly (ADP ribose) synthetase/polymerase (PARP) levels were detected as being relevant to the mechanism of rReg3alpha protection. We therefore conclude that rReg3alpha acts as a protective polypeptide against AP in mice by enhancing Bcl-2 and Bcl-xL expressions and suppressing PARP level. PMID- 26683607 TI - Physiological Markers of Arousal Change with Psychological Treatment for Insomnia: A Preliminary Investigation. AB - OBJECTIVES: The aim of this preliminary study was to evaluate if Sleep Restriction Therapy for insomnia is associated with modifications to physiological arousal, indexed through overnight measures of plasma cortisol concentrations and core body temperature. METHODS: In a pre-to-post open label study design, eleven patients with chronic and severe Psychophysiological Insomnia underwent 5 weeks of Sleep Restriction Therapy. RESULTS: Eight (73%) patients out of 11 consented completed therapy and showed a decrease in insomnia severity pre-to-post treatment (mean (SD): 18.1 (2.8) versus 8.4 (4.8); p = .001). Six patients were analyzed with pre-to-post overnight measures of temperature and cortisol. Contrary to our hypothesis, significantly higher levels of plasma cortisol concentrations were found during the early morning at post treatment compared to baseline (p < .01), while no change was observed in the pre sleep phase or early part of the night. Core body temperature during sleep was however reduced significantly (overall mean [95% CI]: 36.54 ( degrees C) [36.3, 36.8] versus 36.45 [36.2, 36.7]; p < .05). CONCLUSIONS: Sleep Restriction Therapy therefore was associated with increased early morning cortisol concentrations and decreased core body temperature, supporting the premise of physiological changes in functioning after effective therapy. Future work should evaluate change in physiological variables associated with clinical treatment response. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTR 12612000049875. PMID- 26683608 TI - Cell Tracking Accuracy Measurement Based on Comparison of Acyclic Oriented Graphs. AB - Tracking motile cells in time-lapse series is challenging and is required in many biomedical applications. Cell tracks can be mathematically represented as acyclic oriented graphs. Their vertices describe the spatio-temporal locations of individual cells, whereas the edges represent temporal relationships between them. Such a representation maintains the knowledge of all important cellular events within a captured field of view, such as migration, division, death, and transit through the field of view. The increasing number of cell tracking algorithms calls for comparison of their performance. However, the lack of a standardized cell tracking accuracy measure makes the comparison impracticable. This paper defines and evaluates an accuracy measure for objective and systematic benchmarking of cell tracking algorithms. The measure assumes the existence of a ground-truth reference, and assesses how difficult it is to transform a computed graph into the reference one. The difficulty is measured as a weighted sum of the lowest number of graph operations, such as split, delete, and add a vertex and delete, add, and alter the semantics of an edge, needed to make the graphs identical. The measure behavior is extensively analyzed based on the tracking results provided by the participants of the first Cell Tracking Challenge hosted by the 2013 IEEE International Symposium on Biomedical Imaging. We demonstrate the robustness and stability of the measure against small changes in the choice of weights for diverse cell tracking algorithms and fluorescence microscopy datasets. As the measure penalizes all possible errors in the tracking results and is easy to compute, it may especially help developers and analysts to tune their algorithms according to their needs. PMID- 26683609 TI - Factors associated with radiation therapy incompletion for patients with early stage breast cancer. AB - PURPOSE: The purpose of the study was to examine factors associated with adjuvant radiation treatment (RT) incompletion for women with breast cancer within a large national cancer database. METHODS: We identified 394,334 women diagnosed with stage I-III breast cancer during 2004-2012 in the national cancer database who initiated adjuvant external beam adjuvant RT and examined the proportion of women not completing treatment. We used multivariable logistic regression to examine patient, clinical, and facility factors associated with RT incompletion for those who had breast-conserving surgery (BCS), defined as <15 fractions and <3990 centiGray [cGy] (accounting for adoption of hypofractionation), and mastectomy (PMRT, defined as <5000 cGy and <25 fractions), separately. We also examined RT incompletion after BCS using more traditional definitions of <25 fractions and <4500 cGy for diagnosis years <=2010. RESULTS: Among the 319,003 women who underwent BCS and the 75,331 women who underwent mastectomy and initiated RT, 98.4 and 97.8 % completed radiation, respectively. In adjusted analyses, older age was associated with RT incompletion (odds ratio [O.R.] for age >=80 = 2.53 for BCS-treated, 95 % confidence interval [CI] 2.19-2.92; O.R. for PMRT incompletion = 2.33, 95 % CI 1.84-2.96; both versus age <50). In addition, those with >=2 comorbidities and lower-risk disease had higher odds of RT incompletion. After defining RT completion using more traditional definitions, 94.0 % completed treatment. CONCLUSIONS: Reassuringly, we found a very low proportion of patients not completing RT, though we observed a higher likelihood for treatment incompletion in some sub-groups, most notably older women. Further studies should focus on reasons for treatment discontinuation in populations at risk for suboptimal treatment. PMID- 26683610 TI - Opioids should be last resort to treat chronic pain, says draft CDC guideline. PMID- 26683611 TI - Correction: Conditioned Medium from Hypoxic Bone Marrow-Derived Mesenchymal Stem Cells Enhances Wound Healing in Mice. PMID- 26683612 TI - Management of adrenal incidentaloma by laparoscopic transperitoneal anterior and submesocolic approach. AB - PURPOSE: Laparoscopic adrenalectomy (LA) is becoming the main approach for incidentally discovered adrenal masses (adrenal incidentaloma (AI)). The aim of this study was to evaluate the results of LA with a transperitoneal anterior approach for right adrenal lesions and either a transperitoneal anterior or transperitoneal anterior submesocolic approach for the left-sided lesions. METHODS: The study is a retrospective analysis of prospectively collected data. From January 1994 to December 2012, 393 patients underwent LA, 117 of these for an AI. Sixty-seven (57.26 %) and 50 (42.73 %) patients underwent right and left adrenalectomy, respectively. The transperitoneal anterior approach was used in all 67 patients with right lesions (57.26 %) (group A) and in 13 patients with left-sided lesions (11.11 %) (group B). The transperitoneal anterior submesocolic approach was used in the remaining 37 left-sided lesions (31.62 %) (group C). RESULTS: Mean operative time in groups A, B, and C was 104.6 min (range 35-255), 148.9 min (range 80-210), and 82.7 min (range 45-230), respectively. One right and one left anterior LA (1.7 %) were converted to open surgery. There were one major and one minor complications (1.7 %). The mean lesion size was 4.73 cm (range 1-10 cm). Mean hospital stay was 3.6 days. CONCLUSIONS: With adequate experience, LA with a transperitoneal anterior approach for AI is a safe and effective procedure. Early control of the adrenal vein with minimal gland manipulation and limited surgical dissection are its major advantages. In case of left LA, the submesocolic approach reduces the operative time significantly. PMID- 26683613 TI - The clinical benefit of cardiac resynchronization therapy optimization using a device-based hemodynamic sensor in a patient with dilated cardiomyopathy: a case report. AB - INTRODUCTION: Results on the evolution of the clinical status of patients undergoing cardiac resynchronization therapy with a defibrillator after automatic optimization of their cardiac resynchronization therapy are scarce. We observed a rapid and important change in the clinical status of our non-responding patient following activation of a sensor capable of weekly atrioventricular and interventricular delays' optimization. CASE PRESENTATION: A 78-year-old Caucasian man presented with dilated cardiomyopathy, left bundle branch block, a left ventricular ejection fraction of 35 %, New York Heart Association class III/IV heart failure, and paroxysmal atrial fibrillation. Our patient was implanted with a cardiac resynchronization device with a defibrillator and the SonRtip atrial lead. Right ventricular and left ventricular leads were also implanted. Because of the recurrence of atrial fibrillation, the automatic optimization was set off at discharge. Consequently, the device did not optimize atrioventricular and interventricular delays (programming at discharge: 125 ms for the atrioventricular delay and 0 ms for the interventriculardelay). Our patient was treated with an anti-arrhythmic drug. Five months after implantation, his clinical status remained impaired (left ventricular ejection fraction = 30 %). The SonR signal amplitude had also decreased from 0.52 g to 0.29 g. Nevertheless, because our patient was no longer presenting with atrial fibrillation, the anti arrhythmic treatment was stopped and the SonR optimization system was activated. After 2 months of automatic cardiac resynchronization therapy with defibrillator optimization, our patient's clinical status had significantly improved (left ventricular ejection fraction = 60 %, New York Heart Association class II) and the SonR signal amplitude had doubled shortly after the first weekly automatic optimization. CONCLUSION: In this non-responding patient, device-based automatic cardiac resynchronization therapy optimization was shown to significantly improve his clinical status. PMID- 26683614 TI - Cloning HSP70 and HSP90 genes of kaluga (Huso dauricus) and the effects of temperature and salinity stress on their gene expression. AB - The genes encoding HSP70 and HSP90 proteins were isolated from kaluga by homologous cloning and rapid amplification of complementary DNA (cDNA) ends (RACE). HSP70 (GenBank accession no. KP050541) and HSP90 (GenBank accession no. KP050542) cDNAs were composed of 2275 and 2718 bp and encoded polypeptides of 650 and 725 amino acids, respectively. Basic Local Alignment Search Tool (BLAST) analysis showed that HSP70 and HSP90 of kaluga shared high identities with those of Acipenser ruthenus, Acipenser schrenckii, and Acipenser baerii (98-99 %). Fluorescent real-time RT-PCR under unstressed conditions revealed that HSP70 and HSP90 were expressed in 11 different tissues of kaluga. Messenger RNA (mRNA) expressions of both HSP70 and HSP90 were highest in the intestine and lowest in the muscle. In addition, the patterns of mRNA expression of HSP70 and HSP90 were similar, although the level of expression was more in HSP90 than in HSP70 (P < 0.05).We also analyzed patterns of HSP70 and HSP90 expression in the muscle, gill, and liver of kaluga under different combinations of temperature and salinity stress, including temperatures of 4,10, 25, and 28 degrees C at 0 ppt salinity, and salinities of 10, 20, 30, and 40 ppt at 16 degrees C, where 16 degrees C at 0 ppt (parts per thousand) served as the control. We found that levels of mRNA expression of both HSP70 and HSP90 were highest at 4 degrees C in the muscle, gill, and liver and changed little with salinity stress. These results increase understanding of the mechanisms of stress response of cold freshwater fish. PMID- 26683616 TI - Burden of Sexual Dysfunction. AB - Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at L53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society. PMID- 26683615 TI - HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter. AB - BACKGROUND: Intracellular defense proteins, also referred to as restriction factors, are capable of interfering with different steps of the viral life cycle. Among these, we have shown that Tripartite motif 22 (TRIM22) suppresses basal as well as phorbol ester-induced HIV-1 long terminal repeat (LTR)-mediated transcription, independently of its E3 ubiquitin ligase activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) binding to the U3 region and Tat interaction with the TAR region of the HIV-1 LTR. As basal HIV-1 transcription is driven by the transcription factor specificity protein 1 (Sp1), we have investigated whether TRIM22 could interfere with Sp1-driven transcriptional activation of the HIV-1 LTR. FINDINGS: 293T cells, devoid of endogenous TRIM22 expression, were transfected with a TRIM22-expressing plasmid together with reporter plasmids driven by the HIV-1 LTR promoter either containing or lacking Sp1 binding sites or with reporter plasmids driven by non viral promoter sequences either containing or lacking the three Sp1 binding sites from the HIV-1 LTR. These reporter assays showed that TRIM22 efficiently inhibited Sp1-driven transcription. Knocking down TRIM22 expression in the CD4(+) SupT1 T cell line increased the replication of Sp1-dependent HIV-1 variants. TRIM22 did not interact with Sp1, but prevented binding of Sp1 to the HIV-1 promoter, as demonstrated in protein-DNA pull down and chromatin immunoprecipitation assays. CONCLUSION: TRIM22 acts as a suppressor of basal HIV 1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter. PMID- 26683617 TI - Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis. AB - OBJECTIVES: Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. METHODS: We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981-2009 for 16 Indian states by sex (comprising of India's 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under five mortality towards crossover. FINDINGS: India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). CONCLUSIONS: For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1-59 months in high child mortality areas can help India to attain this crossover early. PMID- 26683618 TI - Is early rehabilitation a myth? Physical inactivity in the first week after myocardial infarction and stroke. AB - PURPOSE: To compare physical activity levels of patients in the first week after myocardial infarction (MI) and stroke. METHOD: We conducted an observational study using behavioural mapping. MI patients were consecutively recruited from Alfred Hospital, Melbourne. Data for stroke patients (Royal Perth Hospital or Austin Hospital, Melbourne) were retrieved from an existing database. Patients were observed for 1 min every 10 min from 8 am to 5 pm. At each observation, the patient's highest level of physical activity, location and people present were recorded. Details of physiotherapy and occupational therapy sessions were recorded by the therapists. RESULTS: Proportion of the day spent physically inactive was lower in MI (n = 32, median 48%) than stroke (n = 125, median 59%) patients, but this difference was not significant in univariate or multivariate (adjusting for age, walking ability and days post-event) regression. Time spent physically active was higher in MI (median 23%) than stroke (median 10%) patients (p = 0.009), but this difference did not survive multivariate adjustment (p = 0.67). More stroke patients (78%) than MI patients (19%) participated in therapy. CONCLUSIONS: This study provides the first objective data on physical activity levels of acute MI patients. While they were more active than acute stroke patients, the difference was largely attributable to walking ability. Implications for rehabilitation In the first week after myocardial infarction, patients spent about half the day physically inactive (even though 81% were able to walk independently). Similar levels of inactivity were seen in a comparable cohort of acute stroke patients, suggesting that environmental factors play an important role. There appears to be wide scope for increasing levels of physical rehabilitation after acute cardiovascular events, though optimal timing and dose remain unclear. PMID- 26683620 TI - Erratum to: A de novo whole gene deletion of XIAP detected by exome sequencing analysis in very early onset inflammatory bowel disease: a case report. PMID- 26683619 TI - Resveratrol preserves the function of human platelets stored for transfusion. AB - Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function. PMID- 26683621 TI - Uterine Tonus Assessment by Midwives versus Patient self-assessment in the active management of the third stage of labor (UTAMP): study protocol for a randomized controlled trial. AB - BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and accounts for one third of maternal deaths in low-income and middle-income countries. PPH can be prevented by active management of the third stage of labor (AMTSL), a series of steps recommended by the World Health Organization to be performed by skilled birth attendants (SBAs). Task shifting in the AMTSL step of uterotonic drugs administration to community health workers, traditional birth attendants and self-administration has been investigated as a strategy to increase access to quality obstetric care considering persistent SBA and facility-based delivery shortages. The aim of this study is to assess task shifting in the final step of AMTSL and compare uterine tonus assessment by a SBA to self-assessment. METHODS AND DESIGN: The study is an individual-level two-arm non-inferiority randomized controlled trial (RCT). A total of 800 women will be recruited in Korle Bu Teaching Hospital in Accra, Ghana. Adult women in labor at term with an expected vaginal delivery who received antenatal instructions for self-assessment of uterine tonus will be eligible for inclusion. Women with an increased risk for PPH will be excluded. Women will be randomized to uterine tone assessment by a skilled birth attendant (midwife) or uterine tone self-assessment (with the safety back-up of a midwife present in case of PPH or uterine atony). Postpartum blood loss will be measured through weighing of disposable mats. The main study endpoints are PPH (>=500 ml blood loss), severe PPH (>=1000 ml blood loss), mean blood loss, and routine maternal and neonatal outcomes. Participants and caregivers will not be blinded given the nature of the intervention. DISCUSSION: A reduction of PPH-related maternal mortality requires full implementation of AMTSL. Task shifting of uterine tone assessment may contribute to increased AMTSL implementation in (clinical) settings where SBAs capacity is constrained. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02223806 , registration August 2014. PACTR: PACTR201402000736158 , registration July 2014. University of Ghana, Medical School Ethical and Protocol Review Committee: MS-Et/M.8-P4.1/2014 2015. PMID- 26683622 TI - Environmental Cues in Double-Occupancy Rooms to Support Patients With Dementia. AB - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of different environmental cues in double-occupancy rooms of an acute care hospital to support patients' abilities to identify their bed and wardrobe. METHODS: The quasi-experiment was conducted on a geriatric ward of an acute care hospital. Patients with dementia were included (n = 42). To test the effectiveness of environmental cues, two rooms were enhanced with the environmental cue "color," two rooms with the cue "number," and two rooms with the cue "patient's name". Four rooms were not redesigned and were used as control rooms. For analysis, we pooled the intervention groups color and number (n = 14) and compared it with the control group (n = 22). RESULTS: The environmental cues color and number were significantly effective to improve the identification of the wardrobe from the third to the fifth day after admission. However, for the 10th-12th day after admission, we found no difference in results. Furthermore, results indicate improvements in the ability to identify the bed by using the environmental cues color and number. CONCLUSIONS: As this study indicated, the environmental cues color and number are helpful for these patients to identify their bed and wardrobe. However, these cues were most effective from the third to the fifth day after admission. To sustain their effectiveness on patients' identification abilities during their hospital stay, we discuss, whether verbal prompting and an ongoing mentioning of such cues, embedded in the daily work of nurses, could be beneficial. PMID- 26683623 TI - Factors associated with nursing students' medication competence at the beginning and end of their education. AB - BACKGROUND: In previous studies, deficiencies in nursing students' medication competence have been highlighted. However, the focus of research has been limited especially to medication calculation competence and factors associated with it. In order to develop undergraduate nursing education and research, an understanding of the individual and learning environmental factors associated with medication competence from a broader approach is warranted. Our aim was therefore to evaluate the theoretical, practical and decision-making competence of nursing students and to identify factors associated with their medication competence at the beginning and end of their education. METHODS: We used a descriptive, correlational study design with a structured instrument including a set of potential associated factors, knowledge test, medication calculation test and patient vignettes. The participants were nursing students at the beginning (n = 328) and at the end of their education (n = 338). Data were analyzed statistically. RESULTS: In the evaluation of theoretical medication competence, the students' mean score over the semesters was 72 % correct answers in a knowledge test. In the evaluation of practical medication competence, the mean score was 74 % correct answers in a medication calculation test. In the evaluation of decision-making competence, the mean score was 57 % correct answers on deciding the best action in the situation given in patient vignettes. At the end of their education, students were able to solve patient vignettes significantly better. Individual factors were most evidently associated with medication competence. At the beginning of their education, students' previous academic success had a stronger association with medication competence. However, at the end of the education students' abilities in self-regulated learning and study motivation were more significant factors. CONCLUSION: The core elements of medication competence are significantly interrelated, highlighting the need to provide integrated and comprehensive medication education throughout the undergraduate education. Students' learning style is associated with medication competence. There is a need for methods to identify and support students having difficulties to self-regulate their learning. To increase the safety of medication care of patients, research focusing on the development of effective teaching methods is needed. This study produced information for future nursing education research in this field, especially for interventional studies. PMID- 26683624 TI - Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s. AB - We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). PMID- 26683626 TI - Cortical PGC-1alpha-Dependent Transcripts Are Reduced in Postmortem Tissue From Patients With Schizophrenia. AB - The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) has been linked to multiple neurological and psychiatric disorders including schizophrenia, but its involvement in the pathophysiology of these disorders is unclear. Experiments in mice have revealed a set of developmentally-regulated cortical PGC-1alpha-dependent transcripts involved in calcium buffering (parvalbumin, PV), synchronous neurotransmitter release (synaptotagmin 2, Syt2; complexin 1, Cplx1) and axonal integrity (neurofilamaent heavy chain, Nefh). We measured the mRNA expression of PGC-1alpha and these transcripts in postmortem cortical tissue from control and schizophrenia patients and found a reduction in PGC-1alpha-dependent transcripts without a change in PGC-1alpha. While control subjects with high PGC-1alpha expression exhibited high PV and Nefh expression, schizophrenia subjects with high PGC-1alpha expression did not, suggesting dissociation between PGC-1alpha expression and these targets in schizophrenia. Unbiased analyses of the promoter regions for PGC-1alpha-dependent transcripts revealed enrichment of binding sites for the PGC-1alpha-interacting transcription factor nuclear respiratory factor 1 (NRF-1). NRF-1 mRNA expression was reduced in schizophrenia, and its transcript levels predicted that of PGC-1alpha-dependent targets in schizophrenia. Interestingly, the positive correlation between PGC-1alpha and PV, Syt2, or Cplx1 expression was lost in schizophrenia patients with low NRF-1 expression, suggesting that NRF-1 is a critical predictor of these genes in disease. These data suggest that schizophrenia involves a disruption in PGC-1alpha and/or NRF-1 associated transcriptional programs in the cortex and that approaches to enhance the activity of PGC-1alpha or transcriptional regulators like NRF-1 should be considered with the goal of restoring normal gene programs and improving cortical function. PMID- 26683625 TI - Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive. AB - INTRODUCTION: Resistance to antipsychotic treatment is a significant clinical problem in patients with schizophrenia with approximately 1 in 3 showing limited or no response to repeated treatments with antipsychotic medication. The neurobiological basis for treatment resistance is unknown but recent evidence implicates glutamatergic function in the anterior cingulate cortex. We examined glutamate levels of chronically ill treatment-resistant patients directly compared to treatment-responsive patients. METHODS: We acquired proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla from 21 treatment-resistant and 20 treatment-responsive patients. All participants had a DSM-IV diagnosis of schizophrenia. Treatment-resistant patients were classified using the modified Kane criteria. The groups were matched for age, sex, smoking status, and illness duration. RESULTS: Glutamate to creatine ratio levels were higher in treatment resistant patients (Mean [SD] = 1.57 [0.24]) than in treatment-responsive patients (Mean[SD] = 1.38 [0.23]), (T[35] = 2.34, P = .025, 2-tailed), with a large effect size of d = 0.76. A model assuming 2 populations showed a 25% improvement in the fit of the Akaike weights (0.55) over a model assuming 1 population (0.44), producing group values almost identical to actual group means. DISCUSSION: Increased anterior cingulate glutamate level is associated with treatment-resistant schizophrenia. This appears to be a stable neurobiological trait of treatment-resistant patients. We discuss possible explanations for glutamatergic dysfunction playing a significant role in resistance to conventional antipsychotic treatments, which are all dopamine-2 receptor blockers. Our findings suggest that glutamatergic treatments may be particularly effective in resistant patients and that 1H-MRS glutamate indices can potentially have clinical use. PMID- 26683628 TI - Production and Perception of the /i/-/I/ Vowel Contrast: The Case of L2-Dominant Early Learners of English. AB - The present study explored the production and perception of the /i/-/I/ vowel contrast in second language (L2)-dominant early learners of American English who no longer fluently speak their first language (L1, Spanish). The production task analyzed the extent to which the early learner group differed from controls (native English speakers and L1-Spanish late-onset learners of English) with regard to duration and spectral centroids. The perception experiment examined how these early learners classified resynthesized stimuli drawn from the /i/-/I/ contrast using distinct acoustic cues - spectral and temporal - in a 2 alternative forced choice identification task. The first experiment revealed that the early learners produced the contrast in a native-like manner in terms of the spectral envelope and duration use. The second experiment found that early learners differed from both control groups in how they categorized the /i/-/I/ continua based on spectrum and duration, and the extent to which they rely on these two cues. The effects of linguistic experience on L2 phonetic behavior are discussed. PMID- 26683629 TI - Experience with the Histrelin Implant in Pediatric Patients. AB - The histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers. Inserted subcutaneously, the 50-mg implant provides continuous release of the potent gonadotropin-releasing hormone analog (GnRHa) histrelin. Profound suppression of the hypothalamic-pituitary-gonadal (HPG) axis occurs within 1 month of its placement resulting in pubertal arrest, attenuation of skeletal advancement and a progressive increase in predicted adult height. Although marketed for annual use, suppression lasting 2 years from a single implant has been demonstrated. Placing and removing the device is a minor outpatient procedure easily accomplished by a pediatric surgeon using local anesthesia. The major downside to the implant is a ~25% rate of breakage upon removal. Information about the recovery of the HPG axis following histrelin explantation is limited but suggests an average time to menarche comparable with depot GnRHa formulations albeit with wide individual variation. PMID- 26683627 TI - The value of core lab stress echocardiography interpretations: observations from the ISCHEMIA Trial. AB - BACKGROUND: Stress echocardiography (SE) is dependent on subjective interpretations. As a prelude to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial, potential sites were required to submit two SE, one with moderate or severe left ventricular (LV) myocardial ischemia and one with mild ischemia. We evaluated the concordance of site and core lab interpretations. METHODS: Eighty-one SE were submitted from 41 international sites. Ischemia was classified by the number of new or worsening segmental LV wall motion abnormalities (WMA): none, mild (1 or 2) or moderate or severe (3 or more) by the sites and the core lab. RESULTS: Core lab classified 6 SE as no ischemia, 35 mild and 40 moderate or greater. There was agreement between the site and core in 66 of 81 total cases (81%, weighted kappa coefficient [K] =0.635). Agreement was similar for SE type - 24 of 30 exercise (80%, K = 0.571) vs. 41 of 49 pharmacologic (84%, K = 0.685). The agreement between poor or fair image quality (27 of 36 cases, 75%, K = 0.492) was not as good as for the good or excellent image quality cases (39 of 45 cases, 87%, K = 0.755). Differences in concordance were noted for degree of ischemia with the majority of discordant interpretations (87%) occurring in patients with no or mild LV myocardial ischemia. CONCLUSIONS: While site SE interpretations are largely concordant with core lab interpretations, this appears dependent on image quality and the extent of WMA. Thus core lab interpretations remain important in clinical trials where consistency of interpretation across a range of cases is critical. TRIAL REGISTRATION: ClinicalTrials.gov NCT01471522. PMID- 26683630 TI - Quinolone Resistance Mechanisms Among Salmonella enterica in Malaysia. AB - The prevalence of quinolone-resistant Salmonella enterica is on the rise worldwide. Salmonella enterica is one of the major foodborne pathogens in Malaysia. Therefore, we aim to investigate the occurrence and mechanisms of quinolone resistance among Salmonella strains isolated in Malaysia. A total of 283 Salmonella strains isolated from food, humans, and animals were studied. The disk diffusion method was used to examine the quinolone susceptibility of the strains, and the minimum inhibitory concentration (MIC) values of nalidixic acid and ciprofloxacin were also determined. DNA sequencing of the quinolone resistance-determining regions (QRDRs) of gyrase and topoisomerase IV genes and the plasmid-borne qnr genes was performed. The transfer of the qnr gene was examined through transconjugation experiment. A total of 101 nalidixic acid resistant Salmonella strains were identified. In general, all strains were highly resistant to nalidixic acid (average MICNAL, 170 MUg/ml). Resistance to ciprofloxacin was observed in 30.7% of the strains (1 <= MICCIP <= 2 MUg/ml). Majority of the strains contained missense mutations in the QRDR of gyrA (69.3%). Silent mutations were frequently detected in gyrB (75.2%), parC (27.7%), and parE (51.5%) within and beyond the QRDRs. Novel mutations were detected in parC and parE. The plasmid-borne qnrS1 variant was found in 36.6% of the strains, and two strains were found to be able to transfer the qnrS1 gene. Overall, mutations in gyrA and the presence of qnrS1 genes might have contributed to the high level of quinolone resistance among the strains. Our study provided a better understanding on the status of quinolone resistance among Salmonella strains circulating in Malaysia. PMID- 26683631 TI - Scientific Significance of Clinically Insignificant FcgammaRIIIa-V158F Polymorphism. AB - Kenkre and colleagues report the absence of correlation between FcgammaRIIIa V158F polymorphism and rituximab response in follicular lymphoma patients, a result which is in contrast with prior studies. This discrepancy recalls that many other factors (from the host and from the tumor) may influence the efficacy of rituximab in vivo. PMID- 26683633 TI - Validity of Self-Reported Physical Fitness and Body Mass Index in a Military Population. AB - Many epidemiological studies rely on valid physical fitness data. The purpose of this investigation was to assess the validity of self-reported Army Physical Fitness Test (APFT) data and determine whether men and women recall APFT performance differently. U.S. Army soldiers (N = 1,047) completed a survey, including questions on height, weight, and most recent APFT performance. Height, weight, and APFT performance were also obtained from unit records. The mean +/- SDs for unit and self-reported push-up repetitions were 63.5 +/- 13.1 and 66.3 +/ 14.0 for men and 37.7 +/- 12.8 and 40.2 +/- 12.8 for women, respectively. The mean +/- SD for unit- and self-reported sit-up repetitions were 66.3 +/- 11.4 and 68.1 +/- 12.1 for men and 64.2 +/- 13.6 and 66.5 +/- 12.9 for women, respectively. The mean +/- SD unit- and self-reported 2-mile run times were 15.2 +/- 1.8 and 14.9 +/- 1.6 minutes for men, and 18.0 +/- 2.9 and 17.4 +/- 1.9 minutes for women, respectively. Unit- and self-reported body mass indices (BMIs) (calculated by height and weight) were 26.4 +/- 3.4 and 26.3 +/- 3.6 for men and 24.6 +/- 2.8 and 24.2 +/- 3.3 for women. Correlations between unit- and self reported scores for push-ups, sit-ups, 2-mile run, height, weight, and BMI were 0.82, 0.78, 0.85, 0.87, 0.97, and 0.88 for men and 0.86, 0.84, 0.87, 0.78, 0.98, and 0.78 for women, respectively. On average, men and women slightly overreported performance on the APFT and overestimated height, resulting in underestimated BMI. There was no difference in recall ability between men and women (p > 0.05). The very good to excellent correlations (r = 0.78-0.98) between unit- and self reported scores indicate that self-reported data are valid for capturing physical fitness performance in this population. PMID- 26683632 TI - New Strategies in Bladder Cancer: A Second Coming for Immunotherapy. AB - Urothelial bladder cancer (UBC) remains one of the most common and deadly cancers worldwide, and platinum-based chemotherapy, which has been the standard-of-care in metastatic bladder cancer, has had limited success in improving outcomes for patients. The recent development and translation of therapeutic strategies aimed at harnessing the immune system have led to durable and prolonged survival for patients with several different cancers, including UBC. In this review, we discuss new findings in bladder cancer immunotherapy, including recent successes with immune checkpoint blockade. We also discuss therapeutic cancer vaccines and highlight several additional immunotherapy modalities in early stages of development. PMID- 26683634 TI - A Nanoengineered Conductometric Device for Accurate Analysis of Elemental Mercury Vapor. AB - We developed a novel conductometric device with nanostructured gold (Au) sensitive layer which showed high-performance for elemental mercury (Hg(0)) vapor detection under simulated conditions that resemble harsh industrial environments. That is, the Hg(0) vapor sensing performance of the developed sensor was investigated under different operating temperatures (30-130 degrees C) and working conditions (i.e., humid) as well as in the presence of various interfering gas species, including ammonia (NH3), hydrogen sulfide (H2S), nitric oxide (NO), carbon mono-oxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), hydrogen (H2), methane (CH4), and volatile organic compounds (VOCs) such as ethylmercaptan (EM), acetaldehyde (MeCHO) and methyl ethyl ketone (MEK) among others. The results indicate that the introduction of Au nanostructures (referred to as nanospikes) on the sensor's surface enhanced the sensitivity toward Hg(0) vapor by up-to 450%. The newly developed sensor exhibited a limit of detection (LoD) (~35 MUg/m(3)), repeatability (~94%), desorption efficiency (100%) and selectivity (~93%) when exposed to different concentrations of Hg(0) vapor (0.5 to 9.1 mg/m(3)) and interfering gas species at a chosen operating temperature of 105 degrees C. Furthermore, the sensor was also found to show 91% average selectivity when exposed toward harsher industrial gases such as NO, CO, CO2, and SO2 along with same concentrations of Hg(0) vapor in similar operating conditions. In fact, this is the first time a conductometric sensor is shown to have high selectivity toward Hg(0) vapor even in the presence of H2S. Overall results indicate that the developed sensor has immense potential to be used as accurate online Hg(0) vapor monitoring technology within industrial processes. PMID- 26683635 TI - Selective novel inverse agonists for human GPR43 augment GLP-1 secretion. AB - GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A 404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog. Through structure-activity relationship (SAR), we also found active compound named as BTI-A-292. These regulators increased the cyclic AMP level and reduced acetate-induced cytoplasmic Ca(2+) level. Furthermore, we show that they modulated the downstream signaling pathways of GPR43, such as ERK, p38 MAPK, and NF-kappaB. It was surprising that two compounds augmented the secretion of glucagon-like peptide 1 (GLP-1) in NCI-H716 cell line. Collectively, these novel and specific competitive inhibitors regulate all aspects of GPR43 signaling and the results underscore the therapeutic potential of them. PMID- 26683636 TI - Antinociceptive effects of a new sigma-1 receptor antagonist (N-(2-morpholin-4-yl ethyl)-2-(1-naphthyloxy)acetamide) in two types of nociception. AB - Pain has become an active clinical challenge due its etiological heterogeneity, symptoms and mechanisms of action. In the search for new pharmacological therapeutic alternatives, sigma receptors have been proposed as drug targets. This family consists of sigma-1 and sigma-2 receptors. The sigma-1 system is involved in nociception through its chaperone activity. Additionally, it has been shown that agonist to these receptors promote related sensitisation and pain hypersensitisation, suggesting the possible use of antagonists for sigma-1 receptors as an alternative therapy. The aim of this study was to evaluate the antinociceptive effect of a new sigma-1 receptor antagonist N-(2-morpholin-4-yl ethyl)-2-(1-naphthyloxy)acetamida (NMIN) in two types of pain (arthritic and neuropathic) and to compare its efficacy and potency with reference drugs. The antinociceptive effects of NMIN were quantitatively evaluated using the pain induced functional impairment model in the rat and the acetone test in a rat model of neuropathic pain. NMIN (sigma-1 receptor affinity of 324nM) did not show any antinociceptive activity in the arthritic pain model but showed a dose dependent anti-allodynic effect in neuropathic pain. NMIN showed a similar efficacy compared to the effects obtained with morphine and the sigma-1 antagonist BD-1063. However, these reference drugs showed increased potency compared with NMIN. Our results suggest that sigma-1 receptors may play an important direct role in neuropathic pain but not in arthritic pain, supporting the hypothesis that NMIN may be useful for the treatment of neuropathic pain. PMID- 26683637 TI - Treatment with tanshinone IIA suppresses disruption of the blood-brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis. AB - Tanshinone IIA (TSIIA), one of the major bioactive components of the traditional Chinese herb Salvia miltiorrhiza, has been reported to have both anti inflammatory and immunoregulatory effects. The effect of treatment with TSIIA in multiple sclerosis, an autoimmune inflammatory neurodegenerative disease, however, remains poorly understood. In the present study, experimental autoimmune encephalomyelitis (EAE), a classical experimental model of MS, was used to investigate the therapeutic effect of TSIIA. TSIIA attenuated motor dysfunction and improved inflammation and demyelination associated with EAE in a dose dependent manner. TSIIA also significantly reduced the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1), and protected the integrity of the blood-brain barrier (BBB) by increasing the expression of critical endothelial tight junction (TJ) proteins. TSIIA also inhibited the expression of some adhesion molecules and chemokines, which are considered to be critical for adhesion of immune cells and migration across the BBB. TSIIA was thus shown to be effective in the treatment of EAE through preventing the infiltration of immune cells into the CNS, strengthening the integrity of the BBB and decreasing the numbers of adhesion molecules and chemokines. PMID- 26683638 TI - Impairing effects of angiotensin-converting enzyme inhibitor Captopril on bone of normal mice. AB - There are contradicting results about the effects of angiotensin-converting enzyme inhibitors (ACEIs) on bones. This study was aimed to investigate the effect of ACEI, Captopril, on bone metabolism and histology as well as the action of Captopril on skeletal renin-angiotensin system (RAS) and bradykinin receptor pathway in normal male mice. The urine, serum, tibias and femurs from normal control mice and Captopril-treated (10mg/kg) mice were collected for biochemical, histological and molecular analyses after drug administration for eight weeks. The mice after the treatment with Captopril had a significant decrease of serum testosterone level. The histological measurements showed the loss of trabecular bone mass and trabecular bone number, and the breakage of trabecular bone network as well as the changes of chondrocyte zone at epiphyseal plate in Captopril treated mice. The defect of Captopril on trabecular bone was reflected by the quantitative bio-parameters from micro-CT. The expression of renin receptor and bradykinin B2 receptor (B2R) was significantly up-regulated in tibia of mice upon to the Captopril treatment, which decreased the ratio of OPG/RANKL and the expression of osteoblastic factor RUNX2. Furthermore, Captopril treatment resulted in the increase of pAkt/Akt and pNFkappaB expression in tibia. The present study revealed the impairing effects of Captopril on bone via interfering with the circulating sex hormone level and B2R pathway, which suggests that the bone metabolism of patients need to be carefully monitored when being prescribed for ACEIs. PMID- 26683639 TI - Silent new ischemic lesions after index stroke and the risk of future clinical recurrent stroke. AB - OBJECTIVE: To test whether a silent new ischemic lesion (SNIL) on MRI after stroke predicted future recurrent ischemic stroke or vascular events. METHODS: In this prospective study, we analyzed data from patients presenting with acute ischemic stroke who underwent MRI <24 hours and 5 and 30 days after symptom onset. The presence of a SNIL at 5 (5D-SNIL) and 30 (30D-SNIL) days was determined on diffusion-weighted and fluid-attenuated inversion recovery images. Patients were contacted every 3-6 months to identify recurrent clinical events. The log-rank test and Cox proportional hazard model were used to estimate the hazard ratio of recurrent ischemic stroke and composites of recurrent ischemic stroke, transient ischemic attack, acute coronary syndrome, and vascular death. RESULTS: The 5D- and 30D-SNILs were found in 24.4% (66/270) and 7.4% (19/256) of patients. During the 5-year follow-up, clinical events were observed in 42 patients (15.6%). The 5D- and 30D-SNIL independently predicted recurrent ischemic stroke (hazard ratio [95% confidence interval] 2.9 [1.3-6.4] and 9.6 [4.1-22.1], respectively) and composite vascular events (2.4 [1.3-4.5] and 6.1 [3.1-12.4], respectively). CONCLUSIONS: Patients with a SNIL within the first few weeks after index stroke have an increased risk of recurrent ischemic stroke or vascular events. The presence of a SNIL on MRI could serve as a surrogate endpoint for clinical recurrence in secondary prevention clinical trials. PMID- 26683640 TI - The merging burden of HIV infection and stroke in the developing world. PMID- 26683641 TI - Limb-shaking TIA: Cortical myoclonus associated with ICA stenosis. PMID- 26683643 TI - Cleaved but not endogenous secretory RAGE is associated with outcome in acute ischemic stroke. AB - OBJECTIVE: To investigate the expression patterns of 2 soluble isoforms of receptor for advanced glycation end-product (RAGE), including endogenous secretory RAGE (esRAGE) and cleaved RAGE (cRAGE), and their associations with outcome in acute ischemic stroke (IS). METHODS: Acute IS patients (n = 106) and age- and sex-matched controls (n = 150) were recruited. Plasma levels of total soluble RAGE (sRAGE) and esRAGE in patients at <48 hours and 48-72 hours after IS and in controls were measured by ELISA. The level of cRAGE was calculated by subtracting the level of sRAGE from that of esRAGE. Poor outcome was defined as modified Rankin Scale score >2 at 3 months after stroke. RESULTS: The plasma levels of cRAGE were significantly higher and correlated to those of esRAGE (p < 0.001). The plasma levels of esRAGE and cRAGE were both significantly higher in IS patients <48 hours and 48-72 hours after onset than in controls, but only level of cRAGE at <48 hours was independently associated with poor outcome after adjusting for clinical variables (odds ratio 2.44; 95% confidence interval 1.16 5.16; p = 0.019). CONCLUSION: The plasma level of cRAGE at <48 hours after IS, rather than esRAGE, is a significant predictor of acute IS outcome. PMID- 26683644 TI - Hepatitis C virus infection in inclusion body myositis: A case-control study. AB - OBJECTIVE: To clarify whether there is any association between inclusion body myositis (IBM) and hepatitis C virus (HCV) infection. METHODS: We assessed the prevalence of HCV infection in 114 patients with IBM whose muscle biopsies were analyzed pathologically for diagnostic purpose from 2002 to 2012 and in 44 age matched patients with polymyositis diagnosed in the same period as a control by administering a questionnaire survey to the physicians in charge. We also compared clinicopathologic features including the duration from onset to development of representative symptoms of IBM and the extent of representative pathologic changes between patients with IBM with and without HCV infection. RESULTS: A significantly higher number of patients with IBM (28%) had anti-HCV antibodies as compared with patients with polymyositis (4.5%; odds ratio 8.2, 95% confidence interval 1.9-36) and the general Japanese population in their 60s (3.4%). Furthermore, between patients with IBM with and without HCV infection, we did not find any significant difference in the clinicopathologic features, indicating that the 2 groups have essentially the same disease regardless of HCV infection. CONCLUSION: Our results provide the statistical evidence for an association between IBM and HCV infection, suggesting a possible pathomechanistic link between the 2 conditions. PMID- 26683642 TI - Predictors for atrial fibrillation detection after cryptogenic stroke: Results from CRYSTAL AF. AB - OBJECTIVE: We assessed predictors of atrial fibrillation (AF) in cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an insertable cardiac monitor (ICM). METHODS: We studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. We assessed whether age, sex, race, body mass index, type and severity of index ischemic event, CHADS2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models. RESULTS: Among 221 patients randomized to ICM (age 61.6 +/- 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [HR] per decade 2.0 [95% confidence interval 1.4-2.8], p = 0.002), CHADS2 score (HR 1.9 per one point [1.3-2.8], p = 0.008), PR interval (HR 1.3 per 10 milliseconds [1.2-1.4], p < 0.0001), premature atrial contractions (HR 3.9 for >123 vs 0 [1.3-12.0], p = 0.009 across quartiles), and diabetes (HR 2.3 [1.0-5.2], p < 0.05). In multivariate analysis, age (HR per decade 1.9 [1.3 2.8], p = 0.0009) and PR interval (HR 1.3 [1.2-1.4], p < 0.0001) remained significant and together yielded an area under the receiver operating characteristic curve of 0.78 (0.70-0.85). The same predictors were found at 36 months. CONCLUSION: Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM. PMID- 26683646 TI - Choroid plexus--CSF system: Recent developments and clinical correlations. PMID- 26683645 TI - Chorea in a patient with cryopyrin-associated periodic syndrome. AB - OBJECTIVE: To describe a patient with cryopyrin-associated periodic syndrome (CAPS) with an uncommon neurologic phenotype and a rare underlying genetic mutation. RESULTS: Our patient had CAPS with a rare NLPR3 missense mutation (p.Tyr859Cys) in exon 6 with chorea as the major symptom. Clinical symptoms were associated with persistent inflammatory changes of the CSF and serum and included elevated anticardiolipin immunoglobulin G; MRI showed prolonged gadolinium enhancement of 2 chronic inflammatory lesions. Conventional immunosuppressive treatment with prednisolone and hydroxychloroquine was insufficient. Neurologic symptoms, laboratory/chemical measures, and MRI abnormalities almost completely normalized following interleukin (IL)-1beta blockade with anakinra. CONCLUSIONS: This case is unique for its uncommon neurologic phenotype, the rare underlying genetic mutation, and the long course of the disease as well as almost complete recovery following appropriate therapy. In addition, the chronic inflammatory white matter lesions observed on brain MRI and the responsiveness to IL-1beta blockade with anakinra are unusual. PMID- 26683647 TI - Viruses in IBM: Hit-and-run, hide and persist, or irrelevant? PMID- 26683648 TI - Clinical features of neuromyelitis optica in children: US Network of Pediatric MS Centers report. AB - OBJECTIVE: To compare clinical features of pediatric neuromyelitis optica (NMO) to other pediatric demyelinating diseases. METHODS: Review of a prospective multicenter database on children with demyelinating diseases. Case summaries documenting clinical and laboratory features were reviewed by an adjudication panel. Diagnoses were assigned in the following categories: multiple sclerosis (MS), acute disseminated encephalomyelitis, NMO, and recurrent demyelinating disease not otherwise specified. RESULTS: Thirty-eight cases of NMO were identified by review panel, 97% of which met the revised International Panel on NMO Diagnosis NMO-SD 2014 criteria, but only 49% met 2006 Wingerchuk criteria. Serum or CSF NMO immunoglobulin G (IgG) was positive in 65% of NMO cases that were tested; however, some patients became seropositive more than 3 years after onset despite serial testing. No patient had positive CSF NMO IgG and negative serum NMO IgG in contemporaneous samples. Other than race (p = 0.02) and borderline findings for sex (p = 0.07), NMO IgG seropositive patients did not differ in demographic, clinical, or laboratory features from seronegatives. Visual, motor, and constitutional symptoms (including vomiting, fever, and seizures) were the most common presenting features of NMO. Initiation of disease modifying treatment was delayed in NMO vs MS. Two years after onset, patients with NMO had higher attack rates, greater disability accrual measured by overall Expanded Disability Status Scale score, and visual scores than did patients with MS. CONCLUSION: The new criteria for NMO spectrum disorders apply well to the pediatric setting, and given significant delay in treatment of NMO compared to pediatric MS and worse short-term outcomes, it is imperative to apply these to improve access to treatment. PMID- 26683649 TI - HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study. AB - OBJECTIVE: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. METHODS: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. RESULTS: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (<=45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4(+) T-lymphocyte count (92 vs 375 cells/mm(3), p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. CONCLUSIONS: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID- 26683650 TI - A method to confer Protein L binding ability to any antibody fragment. AB - Recombinant antibody single-chain variable fragments (scFv) are difficult to purify homogeneously from a protein complex mixture. The most effective, specific and fastest method of purification is an affinity chromatography on Protein L (PpL) matrix. This protein is a multi-domain bacterial surface protein that is able to interact with conformational patterns on kappa light chains. It mainly recognizes amino acid residues located at the VL FR1 and some residues in the variable and constant (CL) domain. Not all kappa chains are recognized, however, and the lack of CL can reduce the interaction. From a scFv composed of IGKV10-94 according to IMGT(r), it is possible, with several mutations, to transfer the motif from the IGKV12-46 naturally recognized by the PpL, and, with the single mutation T8P, to confer PpL recognition with a higher affinity. A second mutation S24R greatly improves the affinity, in particular by modifying the dissociation rate (kd). The equilibrium dissociation constant (KD) was measured at 7.2 10(-11) M by surface plasmon resonance. It was possible to confer PpL recognition to all kappa chains. This protein interaction can be modulated according to the characteristics of scFv (e.g., stability) and their use with conjugated PpL. This work could be extrapolated to recombinant monoclonal antibodies, and offers an alternative for protein A purification and detection. PMID- 26683651 TI - Acid-Promoted Cross-Dehydrative Aromatization for the Synthesis of Tetraaryl Substituted Pyrroles. AB - Tetraaryl-substituted pyrroles are one important class of luminophores. In this work, an acid-promoted cross-dehydrative aromatization between benzoin and deoxybenzion was developed. This transformation provides an efficient and straightforward path for the synthesis of various aryl group substituted tetraarylpyrroles. Good to excellent yields were obtained through the easy operation with acetic acid and ammonium acetate. PMID- 26683652 TI - Charge Recombination Suppressed by Destructive Quantum Interference in Heterojunction Materials. AB - We show that charge recombination in ordered heterojunctions depends sensitively on the degree of coherent delocalization of charges at the donor-acceptor interface. Depending on the relative sign of the electron and hole transfer integrals, such delocalization can dramatically suppress recombination through destructive quantum interference. This could explain why measured recombination rates are significantly lower than predictions based on Langevin theory for a variety of organic bulk heterojunctions. Moreover, it opens up a design strategy for photovoltaic devices with enhanced efficiencies through coherently suppressed charge recombination. PMID- 26683653 TI - [Bilateral vocal cord paresis after total thyroidectomy]. AB - A 66-year-old female patient complained of hoarseness and dyspnea under exertion following total thyroidectomy. Due to a faulty operating technique both nerves to the vocal cords were damaged. From the operation report it emerged that the dissection was carried out by protecting the border lamellae but the recurrent laryngeal nerve could not be found on both sides. This article presents the external expert opinion, the decision of the arbitration board and the assessment of the case by two specialist physicians. PMID- 26683654 TI - Children's developing knowledge of and reflection about teaching. AB - A sample of 4- to 7-year-olds (N=61) defined "teaching" and described what and how others had taught them as well as what and how they had taught others. Whereas 4- and 5-year-olds were often unable to define teaching, 6- and 7-year olds most frequently defined teaching by describing processes that could cause knowledge change. Children who held process-based definitions were more likely to offer examples of what others had taught them, to identify who had taught them, and to describe being taught through direct instruction. They were also better able to describe how they had taught others. We consider the results in light of previous interviews in which children were asked to define learning, and we discuss the implications for children's developing understanding of the connections among knowledge, learning, and teaching. PMID- 26683655 TI - Ultrasonic probing of cohesive granular media at very low consolidation. AB - In this work, we study sound propagation in different granular media made of magnetite particles, steel particles, and glass beads consolidated under their own weight. We used two ultrasonic non invasive methods, which are found in good agreement, to estimate the longitudinal wave velocity Vp. In the first one, the velocity is determined through the resonance peaks of the powder slab. The second method determines the velocity with the time of flight of a short pulse traveling through the medium. Magnetite and steel samples show dispersive properties below a frequency ~ 10kHz. The increase of attractive forces between particles lead to two competing effects; on one hand the solid fraction decreases and on the other hand the contacts are stiffer. A decrease in solid fraction implies that the number of contacts decreases leading to a decrease in the wave propagation velocity. On the other hand stronger contacts on average lead to an increase of sound velocity. In our experiments an increase in powder cohesion (caused by a decrease of the bead diameter) leads to an increase in sound velocity even though the solid fraction decreases. The same behavior is found in glass beads. These results show the predominant role of cohesive forces on sound propagation in loosely consolidated dry fine powders as well as the accuracy of ultrasonic methods for powder characterization. PMID- 26683656 TI - Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy. AB - BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy. MATERIAL AND METHODS We evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR. RESULTS The ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy. CONCLUSIONS PCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy. PMID- 26683657 TI - Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats. AB - Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric "shells" when computing three distinct anisotropy maps-fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals. PMID- 26683659 TI - Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-kappaB/COX-2 Pathways. AB - Dexmedetomidine has been reported to provide neuroprotection against hypoxia induced damage. However, the underlying mechanisms remain unclear. We examined whether dexmedetomidine's neuroprotective effects were mediated by the NF kappaB/COX-2 pathways. Adult male C57BL/6 mice were subjected to a 30-min hypoxic treatment followed by recovery to normal conditions. They received dexmedetomidine (16 or 160 MUg/kg) or 25 mg/kg atipamezole, an alpha2 adrenoreceptor antagonist, intraperitoneally before exposure to hypoxia. The whole brain was harvested 6, 18, or 36 h after the hypoxia to determine the histopathological outcome and cleaved caspase-3, Bax/Bcl, NF-kappaB, and COX-2 levels. Hypoxia treatment induced significant neurotoxicity, including destruction of the tissue structure and upregulation of the protein levels of caspase-3, the ratio of Bax/Bcl-2, NF-kappaB, and COX-2. Dexmedetomidine pretreatment effectively improved histological outcome and restored levels of caspase-3, the Bax/Bcl-2 ratio, NF-kappaB, and COX-2. Atipamezole reversed the neuroprotection induced by dexmedetomidine. Neuroprotection was achieved by PDTC and NS-398, inhibitors of NF-kappaB and COX-2, respectively. Dexmedetomidine use before hypoxia provides neuroprotection. Inhibition of NF-kappaB/COX-2 pathways activation may contribute to the neuroprotection of dexmedetomidine. PMID- 26683660 TI - WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo. AB - To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO3/Pt nanoparticles that mimic a leukocyte's functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO3/Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye's anterior chamber, we show that WO3/Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer. PMID- 26683661 TI - Purinoreceptor P2X7 Regulation of Ca(2+) Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury. AB - The process of wound healing involves a complex network of signaling pathways working to promote rapid cell migration and wound closure. Activation of purinergic receptors by secreted nucleotides plays a major role in calcium mobilization and the subsequent calcium-dependent signaling that is essential for proper healing. The role of the purinergic receptor P2X7 in wound healing is still relatively unknown. We demonstrate that P2X7 expression increases at the leading edge of corneal epithelium after injury in an organ culture model, and that this change occurs despite an overall decrease in P2X7 expression throughout the epithelium. Inhibition of P2X7 prevents this change in localization after injury and impairs wound healing. In cell culture, P2X7 inhibition attenuates the amplitude and duration of injury-induced calcium mobilization in cells at the leading edge. Immunofluorescence analysis of scratch-wounded cells reveals that P2X7 inhibition results in an overall decrease in the number of focal adhesions along with a concentration of focal adhesions at the wound margin. Live cell imaging of green fluorescent protein-labeled actin and talin shows that P2X7 inhibition alters actin cytoskeletal rearrangements and focal adhesion dynamics after injury. Together, these data demonstrate that P2X7 plays a critical role in mediating calcium signaling and coordinating cytoskeletal rearrangement at the leading edge, both of which processes are early signaling events necessary for proper epithelial wound healing. PMID- 26683658 TI - Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer. AB - Genomic technologies including microarrays and next-generation sequencing have enabled the generation of molecular signatures of prostate cancer. Lists of differentially expressed genes between malignant and non-malignant states are thought to be fertile sources of putative prostate cancer biomarkers. However such lists of differentially expressed genes can be highly variable for multiple reasons. As such, looking at differential expression in the context of gene sets and pathways has been more robust. Using next-generation genome sequencing data from The Cancer Genome Atlas, differential gene expression between age- and stage matched human prostate tumors and non-malignant samples was assessed and used to craft a pathway signature of prostate cancer. Up- and down-regulated genes were assigned to pathways composed of curated groups of related genes from multiple databases. The significance of these pathways was then evaluated according to the number of differentially expressed genes found in the pathway and their position within the pathway using Gene Set Enrichment Analysis and Signaling Pathway Impact Analysis. The "transforming growth factor-beta signaling" and "Ran regulation of mitotic spindle formation" pathways were strongly associated with prostate cancer. Several other significant pathways confirm reported findings from microarray data that suggest actin cytoskeleton regulation, cell cycle, mitogen-activated protein kinase signaling, and calcium signaling are also altered in prostate cancer. Thus we have demonstrated feasibility of pathway analysis and identified an underexplored area (Ran) for investigation in prostate cancer pathogenesis. PMID- 26683662 TI - Exocytosis of Endothelial Lysosome-Related Organelles Hair-Triggers a Patchy Loss of Glycocalyx at the Onset of Sepsis. AB - Sepsis is a systemic inflammatory syndrome induced by bacterial infection that can lead to multiorgan failure. Endothelial surface glycocalyx (ESG) decorating the inner wall of blood vessels is a regulator of multiple vascular functions. Here, we tested a hypothesis that patchy degradation of ESG occurs early in sepsis and is a result of exocytosis of lysosome-related organelles. Time-lapse video microscopy revealed that exocytosis of Weibel-Palade bodies and secretory lysosomes occurred a few minutes after application of lipopolysaccharides to endothelial cells. Two therapeutic maneuvers, a nitric oxide intermediate, NG hydroxy-l-arginine, and culture media conditioned by endothelial progenitor cells reduced the motility of lysosome-related organelles. Confocal and stochastic optical reconstruction microscopy confirmed the patchy loss of ESG simultaneously with the exocytosis of lysosome-related organelles and Weibel-Palade bodies in cultured endothelial cells and mouse aorta. The loss of ESG was blunted by pretreatment with NG-hydroxy-l-arginine or culture media conditioned by endothelial progenitor cells. Moreover, these treatments resulted in a significant reduction in deaths of septic mice. Our data support the hypothesis assigning to stress-induced exocytosis of these organelles the role of a hair trigger for local degradation of ESG that initiates leukocyte infiltration, increase in vascular permeability, and partially accounts for the later rates of morbidity and mortality. PMID- 26683663 TI - Laminins and Nidogens in the Pericellular Matrix of Chondrocytes: Their Role in Osteoarthritis and Chondrogenic Differentiation. AB - The aim of this study was to investigate the role of laminins and nidogen-2 in osteoarthritis (OA) and their potential to support chondrogenic differentiation. We applied immunohistochemistry, electron microscopy, siRNA, quantitative RT-PCR, Western blot, and proteome analysis for the investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. We demonstrate that subunits of laminins appear in OA cartilage and that nidogen-2-null mice exhibit typical osteoarthritic features. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-alpha1, laminin-alpha5, and nidogen-2 in their pericellular matrix, and laminin-alpha1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. Knockdown of nidogen-2 reduced SOX9 expression, whereas it up-regulated RUNX2 expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration. PMID- 26683665 TI - The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility. AB - The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients. PMID- 26683664 TI - Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure. AB - Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1(-/-)) mice were fed a control, cholestyramine-containing, or bile acid-containing diet before azoxymethane (AOM) induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1(-/-) mice reduced bile acid levels and delayed AOM induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure. PMID- 26683666 TI - HIV Promotes NLRP3 Inflammasome Complex Activation in Murine HIV-Associated Nephropathy. AB - Dysregulated growth and loss of podocytes are important features of HIV associated nephropathy. Recently, HIV was reported to induce a new type of programed cell death, pyroptosis, in T lymphocytes through induction of Nod-like receptor protein 3 (NLRP3) inflammasome complexes. We evaluated the role of HIV in podocyte NLRP3 inflammasome formation both in vivo and in vitro. Renal cortical sections of HIV-transgenic mice (Tg26) displayed increased expression of NLRP3, ASC (a CARD protein), caspase-1, and IL-1beta proteins, confirming NLRP3 inflammasome complex formation in podocytes of Tg26 mice. Renal tissues of Tg26 mice also displayed enhanced mRNA levels and protein expressions of inflammasome markers (NLRP3, ASC, and caspase-1, and IL-1beta). Serum of Tg26 mice also showed elevated concentrations of IL-1beta cytokine compared with FVBN mice. HIV induced pyroptosis in a dose- and time-dependent manner within podocytes, a phenotype of inflammasome activation. Caspase-1 inhibitor not only attenuated podocyte expression of caspase-1 and IL-1beta but also provided protection against pyroptosis, suggesting that HIV-induced podocyte injury was mediated by caspase-1 activation. Interestingly, HIV-induced podocyte pyroptosis could be partially inhibited by Tempol (a superoxide dismutase-mimetic agent) and by glyburide (an inhibitor of potassium efflux). These findings suggest that generation of reactive oxygen species and potassium efflux contribute to HIV-induced pyroptosis and NLRP3 inflammasome activation in podocytes. PMID- 26683668 TI - The Mechanism of Action of Lysobactin. AB - Lysobactin, also known as katanosin B, is a potent antibiotic with in vivo efficacy against Staphylococcus aureus and Streptococcus pneumoniae. It was previously shown to inhibit peptidoglycan (PG) biosynthesis, but its molecular mechanism of action has not been established. Using enzyme inhibition assays, we show that lysobactin forms 1:1 complexes with Lipid I, Lipid II, and Lipid II(A)(WTA), substrates in the PG and wall teichoic acid (WTA) biosynthetic pathways. Therefore, lysobactin, like ramoplanin and teixobactin, recognizes the reducing end of lipid-linked cell wall precursors. We show that despite its ability to bind precursors from different pathways, lysobactin's cellular mechanism of killing is due exclusively to Lipid II binding, which causes septal defects and catastrophic cell envelope damage. PMID- 26683670 TI - Correction: Do Longer Intervals between Challenges Reduce the Risk of Adverse Reactions in Oral Wheat Challenges? PMID- 26683667 TI - A Systematic Review and Meta-Analysis of the Campylobacter spp. Prevalence and Concentration in Household Pets and Petting Zoo Animals for Use in Exposure Assessments. AB - Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don't live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992-2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x103cfu/g for petting zoo animals, and 2.9x105cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in Canada and abroad. Within this literature, knowledge gaps were identified, and include: a lack of concentration data reported in the literature for Campylobacter spp. in animal feces, a distinction between ill and diarrheic pets in the reported studies, noted differences in shedding and concentrations for various subtypes of Campylobacter, and consistent reporting between studies. PMID- 26683669 TI - Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier Transform Infrared Imaging Technique. AB - Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice. PMID- 26683671 TI - MAPKs and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis. AB - Molecular hydrogen (H2 ) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis (AP) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein-protein interaction networks of these proteins. The results triggered our interest in mitogen-activated protein kinase (MAPK) and heat shock cognate 71 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK, and activated NF kappaB and the expression of tumor necrosis factor alpha and interleukin-1beta, while simultaneously preventing the translocation of phospho-ERK, phospho-JNK, and phospho-p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression. PMID- 26683672 TI - White House expands opioid addiction response: Treat chronic pain like other chronic conditions, pharmacists say. PMID- 26683673 TI - Treatment of brodifacoum overdose with prothrombin complex concentrate. AB - PURPOSE: A case of brodifacoum overdose and its treatment with prothrombin complex concentrate (PCC) are reported. SUMMARY: A 44-year-old Caucasian woman weighing 62 kg arrived at the emergency department with a chief complaint of lower left leg pain for two days. A computed tomography (CT) scan of the abdomen revealed perihepatic fluid collection (likely a hematoma), a small-bowel intramural hematoma, and blood in the paracolic gutter. A CT scan of the patient's left foot showed soft tissue swelling without evidence of fracture or dislocation. The patient was diagnosed with left extremity compartment syndrome secondary to hematoma and trauma. The patient had a history of depression and anxiety and eventually admitted to ingesting large doses of brodifacoum the week prior with suicidal intentions. The patient was treated with phytonadione 20 mg i.v., 1 unit of fresh frozen plasma (FFP), and 1 unit of packed red blood cells. Laboratory test values measured in the intensive care unit revealed an International Normalized Ratio (INR) of 15, a prothrombin time of >120 seconds, and a partial prothromboplastin time of >180 seconds. After consulting with a local poison center, phytonadione 50 mg i.v., PCC 3100 units, and 4 units of FFP were immediately administered to reverse the patient's coagulopathy. The dose of oral phytonadione was lowered based on INR stability. Once the coagulopathy was stabilized, the patient was transferred to an inpatient psychiatric facility on phytonadione 10 mg daily orally to maintain a stable INR. CONCLUSION: A 44-year old woman who intentionally ingested brodifacoum was successfully treated with phytonadione, PCC, and FFP. PMID- 26683674 TI - Predictive factors for sorafenib-induced hand-foot skin reaction using ordered logistic regression analysis. AB - PURPOSE: Predictive factors for sorafenib-induced hand-foot skin reaction (HFSR) using ordered logistic regression analysis were studied. METHODS: This retrospective analysis evaluated patients admitted to a university hospital in Japan from May 2008 through October 2013. Patients age 20 years or older with relapsed or metastatic renal cell carcinoma, unresectable hepatocellular carcinoma, or gastrointestinal stromal tumor resistant to imatinib and sunitinib were included. Data were manually collected from patients' clinical records and included sex, age, Eastern Cooperative Oncology Group (ECOG) performance status, initial daily dose of sorafenib, duration of sorafenib use, concomitant medications, number of metastases, sites of metastases, physical examination findings, and type of cancer. Laboratory test values related to the patient's medical condition that seemed to influence HFSR or the absorption and pharmacologic effects of sorafenib were also collected. HFSR severity was also assessed. Univariate ordered logistic analysis was performed for HFSR severity outcomes and each candidate independent variable. A multivariate ordered logistic regression model was then constructed using a stepwise forward selection procedure. Data were screened for multicollinearity. RESULTS: Data from 113 patients were evaluated. This analysis identified duration of sorafenib use (odds ratio [OR], 0.0531), use of a proton pump inhibitor (PPI) (OR, 0.351), ECOG performance status (OR, 0.555), C-reactive protein level (OR, 17.74), and male sex (OR, 0.403) as significant factors for the occurrence of HFSR. CONCLUSION: Multivariate logistic regression analysis revealed that short duration of sorafenib use, avoidance of PPIs, good ECOG performance status, high C-reactive protein level, and female sex were predictive factors for the development of HFSR. PMID- 26683675 TI - FDA approves first intranasal naloxone product. PMID- 26683676 TI - Development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy program. AB - PURPOSE: The development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy (OPAT) program in a county teaching hospital are described. SUMMARY: A pharmacist-managed OPAT program was developed and implemented at a county teaching hospital to provide consistent evaluation, approval, and monitoring of patients requiring OPAT for the treatment of infection. The developmental and implementation stages of the OPAT program included (1) a needs assessment, (2) the identification of resources necessary for program operation, (3) delineation of general OPAT program operations and activities of individual OPAT clinicians, (4) the development of patient selection criteria, including a plan of care algorithm, and (5) acquisition of administrative support to approve the program. In this program, the OPAT pharmacist plays an integral role in the management and oversight of OPAT patients, working under a collaborative agreement with infectious diseases physicians. The OPAT pharmacist assists with appropriate patient and regimen selection, confirmation of orders on discharge, assuring that laboratory tests for safety surveillance are performed and evaluated, performing routine monitoring for adverse events and line complications, and assuring the removal of the vascular access device upon the completion of OPAT. CONCLUSION: The OPAT program provides structured monitoring, patient follow-up, and led to improvements in patient outcome with minimization of treatment and line-related adverse events. PMID- 26683677 TI - Proposed changes to 340B program alarm pharmacy chiefs. PMID- 26683678 TI - Development of an algorithm to assess appropriateness of overriding alerts for nonformulary medications in a computerized prescriber-order-entry system. AB - PURPOSE: An algorithm for assessing the appropriateness of physician overrides of clinical decision support alerts triggered by nonformulary medication (NFM) requests is described. METHODS: Data on a random sample of 5000 NFM alert overrides at Brigham and Women's Hospital over a four-year period (2009-12) were extracted from the hospital's computerized prescriber-order-entry (CPOE) system. Through an iterative process, a scheme for categorizing the reasons given by prescribers for alert overrides was developed. A pharmacist and a physician used the categorization scheme to classify and group alert override reasons, and the resultant data guided the development of an algorithm for assessing alert overrides. RESULTS: In free-text comments written in response to NFM alerts, prescribers provided more than 1150 unique reasons to justify formulary deviation. The compiled reasons were analyzed and grouped into nine categories through the iterative process, with a high degree of interrater agreement (kappa = 0.989; 95% confidence interval, 0.985-0.992). An initially developed 30-item "NFM alert override appropriateness algorithm" was simplified to create an 8 question algorithm that was presented to an interdisciplinary team for evaluation, with subsequent refinements for enhanced clinical creditability. The final algorithm can be used by researchers and formulary managers to develop strategies for limiting NFM alert overrides and to avoid the labor-intensive task of creating appropriateness criteria for each NFM. CONCLUSION: A multistep process was used to develop a generalized algorithm for categorizing the appropriateness of reasons given for NFM alert overrides in a CPOE system. PMID- 26683679 TI - CMS finalizes 2016 hospital outpatient payment rule. PMID- 26683680 TI - Cost-avoidance and qualitative analysis of clinical pharmacy interventions by psychiatric pharmacy residents at state psychiatric facilities. AB - PURPOSE: The cost avoidance and quality of clinical interventions made by postgraduate year 2 (PGY2) psychiatric pharmacy residents are analyzed. METHODS: A retrospective database review of clinical interventions made by PGY2 psychiatric pharmacy residents in two state psychiatric facilities from July 1, 2007 through June 30, 2014, was conducted using a clinical intervention documentation software system. Cost avoidance was calculated by multiplying the mean cost of an adverse drug reaction (ADR) by the probability of an ADR occurring had the intervention not occurred. Sensitivity analyses were performed to identify a conservative estimate of cost avoidance and an upper limit estimate of cost avoidance. The significance of an intervention was determined based on the potential of the intervention type to impact patient care. RESULTS: A total of 2,329 clinical interventions were documented by 10 residents during the seven year study period, with a mean of 233 interventions made per resident. Interventions were largely accepted (70.1%), were of moderate significance (61.9%), were associated with management of psychiatric conditions (48.7%), and primarily involved medication adjustments (13.7%), particularly for antipsychotics (24.6%). The estimated overall cost avoidance associated with PGY2 psychiatric pharmacy resident interventions was $406,944 over the study period, with a mean cost avoidance of $40,694 per resident. CONCLUSION: A detailed qualitative analysis revealed that PGY2 psychiatric pharmacy residents' interventions were largely accepted, focused on medication adjustments for psychiatric conditions, and were of moderate significance at two state psychiatric facilities. Antipsychotics were associated with the greatest cost avoidance and total number of interventions. PMID- 26683681 TI - Development of an outpatient clinic to provide pertussis vaccinations to maternity patients and family members. AB - PURPOSE: The implementation of a hospital-based outpatient pertussis prevention program targeting maternity patients and family members is described. SUMMARY: Faced with a rising incidence of pertussis statewide, a large Ohio hospital formed a multidisciplinary team to ensure hospital compliance with current guidelines calling for administration of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine to all maternity patients as well as previously unvaccinated family members and likely neonatal caregivers (i.e., "cocooning"). The team had regularly scheduled meetings to identify and address fiscal, logistic, and practice-related challenges throughout the implementation process. Key challenges included (1) determining the availability of insurance reimbursement for Tdap vaccination services, (2) cultivating support for the vaccination initiative among obstetrics and maternal-fetal medicine specialists, (3) coordinating development and dissemination of educational information to patients and their families at specified points of contact, and (4) establishing an efficient registration process for family members. The outpatient vaccination clinic was located adjacent to the hospital's maternity center in order to provide convenient access. Despite limited clinic hours (three hours daily on weekdays only) and ongoing reimbursement and funding challenges, the program has improved Tdap vaccination rates in the target population and is considered a successful demonstration of the cocooning concept. CONCLUSION: Implementation of an outpatient clinic for neonatal pertussis prevention was well accepted by family members of newborns, and Tdap vaccinations were administered to 329 family members during the first 11 months of clinic operations. PMID- 26683682 TI - Survey to assess procedures for handling cytotoxic drugs in academic research laboratories in the United Kingdom. PMID- 26683683 TI - Blinatumomab: A novel, bispecific, T-cell engaging antibody. AB - PURPOSE: The pharmacology, pharmacodynamics, pharmacokinetics, efficacy in clinical trials, safety and tolerability, and place in therapy of blinatumomab are reviewed. SUMMARY: Blinatumomab is a novel, bispecific, T-cell engaging antibody that targets tumor-associated antigens CD19 and CD3. Blinatumomab was approved through an accelerated pathway for the treatment of Philadelphia (Ph) chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). One Phase II trial found 16 of 21 patients to be negative for minimal residual disease (MRD) after one cycle of treatment, resulting in a response rate of 80%. Another Phase II trial showed an 82% MRD response, even in heavily pretreated patients. The most common adverse events of any grade noted were pyrexia, febrile neutropenia, hypokalemia, and anemia. The most frequently occurring grade 3 or 4 adverse events were febrile neutropenia, neutropenia, and anemia. Cycle 1 is dosed as a 9- MUg/ day continuous i.v. infusion on days 1-7 and a 28-MUg/day continuous i.v. infusion on days 8-28 administered as a four week continuous i.v. infusion, followed by at least two weeks of no treatment. Subsequent cycles are dosed as a 28-MUg/day continuous i.v. infusion on days 1 28, followed by at least two weeks of no treatment, for up to five treatment cycles. CONCLUSION: Blinatumomab is approved as an option for Ph chromosome negative relapsed or refractory B-cell precursor ALL and is a needed addition to the limited treatment options for this difficult-to-treat patient population. Two Phase II clinical trials resulted in impressive results when using blinatumomab as a single agent, resulting in the drug's approval. PMID- 26683684 TI - Clinical pharmacy practice in Egyptian hospitals. PMID- 26683685 TI - Development and validation of a high throughput, closed tube method for the determination of haemoglobin alpha gene (HBA1 and HBA2) numbers by gene ratio assay copy enumeration-PCR (GRACE-PCR). AB - BACKGROUND: Deletions of the alpha-globin genes are the most common genetic abnormalities in the world. Currently multiplex Gap-PCRs are frequently used to identify specific sets of common deletions. However, these assays require significant post-amplification hands on time and cannot be used to identify novel or unexpected deletions. The aim of the current study was to develop a rapid screening test for the detection of all deletions of the alpha-globin genes that can be integrated into a high volume clinical laboratory workflow. METHODS: A gene ratio assay copy enumeration (GRACE) PCR method was developed by simultaneous amplification of targets in the alpha-globin genes (HBA1 and HBA2) and the chloride channel voltage sensitive 7 (CLCN7) reference gene. A novel application of High Resolution Melting (HRM) analysis then allowed rapid determination of alpha-globin gene copy numbers. The assay was validated using 105 samples with previously determined and 62 samples with unknown alpha-globin genotypes. RESULTS: The GRACE-PCR assay detected abnormal alpha-globin gene copy numbers in 108 of the 167 samples evaluated. The results were consistent with those from a commercial reverse hybridization assay and no allele drop out was observed. CONCLUSIONS: We have successfully developed and validated a GRACE-PCR screening test for the detection of deletions and duplications of the alpha globin genes. The assay is based on copy number determination and has the ability to detect both known and novel deletions of the alpha-globin genes. It is a closed tube technique; consequently the risk of amplicon contamination is negligible. Amplification, detection and analysis can be completed within one hour, making it faster, cheaper and simpler than other existing tests and thus well suited as a rapid first step in a clinical laboratory workflow. PMID- 26683686 TI - Unitary GABAergic volume transmission from individual interneurons to astrocytes in the cerebral cortex. AB - Communication between individual GABAergic cells and their target neurons is mediated by synapses and, in the case of neurogliaform cells (NGFCs), by unitary volume transmission. Effects of non-synaptic volume transmission might involve non-neuronal targets, and astrocytes not receiving GABAergic synapses but expressing GABA receptors are suitable for evaluating this hypothesis. Testing several cortical interneuron types in slices of the rat cerebral cortex, we show selective unitary transmission from NGFCs to astrocytes with an early, GABAA receptor and GABA transporter-mediated component and a late component that results from the activation of GABA transporters and neuronal GABAB receptors. We could not detect Ca2+ influx in astrocytes associated with unitary GABAergic responses. Our experiments identify a presynaptic cell-type-specific, GABA mediated communication pathway from individual neurons to astrocytes, assigning a role for unitary volume transmission in the control of ionic and neurotransmitter homeostasis. PMID- 26683687 TI - Beyond repair - family and community reintegration after obstetric fistula surgery: study protocol. AB - BACKGROUND: Obstetric fistula is a debilitating birth injury that affects an estimated 2-3 million women globally, most in sub-Saharan Africa and Asia. The urinary and/or fecal incontinence associated with fistula affects women physically, psychologically and socioeconomically. Surgical management of fistula is available with clinical success rates ranging from 65-95 %. Previous research on fistula repair outcomes has focused primarily on clinical outcomes without considering the broader goal of successful reintegration into family and community. The objectives for this study are to understand the process of family and community reintegration post fistula surgery and develop a measurement tool to assess long-term success of post-surgical family and community reintegration. METHODS: This study is an exploratory sequential mixed-methods design including a preliminary qualitative component comprising in-depth interviews and focus group discussions to explore reintegration to family and community after fistula surgery. These results will be used to develop a reintegration tool, and the tool will be validated within a small longitudinal cohort (n = 60) that will follow women for 12 months after obstetric fistula surgery. Medical record abstraction will be conducted for patients managed within the fistula unit. Ethical approval for the study has been granted. DISCUSSION: This study will provide information regarding the success of family and community reintegration among women returning home after obstetric fistula surgery. The clinical and research community can utilize the standardized measurement tool in future studies of this patient population. PMID- 26683688 TI - Enhancing the lipid productivity of yeasts with trace concentrations of iron nanoparticles. AB - Oxidative stress induced by zero-valent iron nanoparticles (nZVIs) was used to improve lipid accumulation in various oleaginous and non-oleginous yeasts-Candida sp., Kluyveromyces polysporus, Rhodotorula glutinis, Saccharomyces cerevisiae, Torulospora delbrueckii, Trichosporon cutaneum, and Yarrowia lipolytica. The highest lipid yields occurred at 9-13 mg/L nZVIs. Gas chromatography-mass spectrometry was used for the quantitative and qualitative analysis of the fatty acids. It showed an increasing abundance of polyunsaturated fatty acids, especially essential linoleic acid, in the presence of nZVIs. Our results suggest that nZVIs can be used to improve not only lipid production by oleaginous microorganisms but also the nutritional value of biosynthesized unsaturated fatty acids. PMID- 26683689 TI - Understanding Herd Immunity. AB - Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity. PMID- 26683691 TI - Papillon-Lefevre syndrome with palmoplantar keratoderma and periodontitis, a rare cause of pyrexia of unknown origin: a case report. AB - INTRODUCTION: Papillon-Lefevre Syndrome is a rare autosomal recessive disorder characterized by diffuse, transgradient palmoplantar keratoderma, destructive periodontitis beginning in childhood, premature loss of primary teeth, and frequent cutaneous and systemic pyogenic infections. Pyogenic liver abscess is an uncommon presentation of the disease present in this case. CASE PRESENTATION: A 16-year-old Punjabi, Pakistani boy presented to the outpatient department of a tertiary-care hospital of Lahore with high-grade fever of 2 months duration. He had been treated for a pyogenic liver abscess 2 years back with antibiotics followed by incision and drainage. He had poor orodental hygiene, palmoplantar keratoderma and periodontitis. His parents had history of consanguinity. His brother and two cousins had similar skin lesions and were edentulous. An orthopentogram showed atrophy of the alveolar bone. He was treated with broad spectrum antibiotics, and antipyretics for systemic infection. Multivitamins, topical steroids, topical keratolytics and emollients were used for his dermatological issues. CONCLUSIONS: Our patient was successfully treated. His fever settled and his skin lesions improved with antibiotics, topical steroids and keratolytics. He was sent home and was asked to return for follow-up on a monthly basis. PMID- 26683690 TI - Genome Wide Methylome Alterations in Lung Cancer. AB - Aberrant cytosine 5-methylation underlies many deregulated elements of cancer. Among paired non-small cell lung cancers (NSCLC), we sought to profile DNA 5 methyl-cytosine features which may underlie genome-wide deregulation. In one of the more dense interrogations of the methylome, we sampled 1.2 million CpG sites from twenty-four NSCLC tumor (T)-non-tumor (NT) pairs using a methylation sensitive restriction enzyme- based HELP-microarray assay. We found 225,350 differentially methylated (DM) sites in adenocarcinomas versus adjacent non-tumor tissue that vary in frequency across genomic compartment, particularly notable in gene bodies (GB; p<2.2E-16). Further, when DM was coupled to differential transcriptome (DE) in the same samples, 37,056 differential loci in adenocarcinoma emerged. Approximately 90% of the DM-DE relationships were non canonical; for example, promoter DM associated with DE in the same direction. Of the canonical changes noted, promoter (PR) DM loci with reciprocal changes in expression in adenocarcinomas included HBEGF, AGER, PTPRM, DPT, CST1, MELK; DM GB loci with concordant changes in expression included FOXM1, FERMT1, SLC7A5, and FAP genes. IPA analyses showed adenocarcinoma-specific promoter DMxDE overlay identified familiar lung cancer nodes [tP53, Akt] as well as less familiar nodes [HBEGF, NQO1, GRK5, VWF, HPGD, CDH5, CTNNAL1, PTPN13, DACH1, SMAD6, LAMA3, AR]. The unique findings from this study include the discovery of numerous candidate The unique findings from this study include the discovery of numerous candidate methylation sites in both PR and GB regions not previously identified in NSCLC, and many non-canonical relationships to gene expression. These DNA methylation features could potentially be developed as risk or diagnostic biomarkers, or as candidate targets for newer methylation locus-targeted preventive or therapeutic agents. PMID- 26683693 TI - NIH plans to be more nimble and innovative. PMID- 26683692 TI - Fatigue as a manifestation of psychosocial distress in a low-income country: a population-based panel study. AB - OBJECTIVE: Fatigue is a common complaint worldwide and associated with disability and high health service use costs. We tested the hypothesis that maternal fatigue would be associated independently with maternal common mental disorder ('maternal CMD') in a rural, low-income country setting. METHODS: The analysis was conducted using data from a population-based cohort located in the Butajira demographic surveillance site, Ethiopia. A total of 1065 women were recruited in pregnancy and followed up to 2.5 (n = 1009; 94.7%) and 3.5 years post-partum (n = 989; 92.9%). Maternal CMD symptoms were measured using a locally validated version of the Self-Reporting Questionnaire and fatigue was measured using a dichotomised item from the Patient Health Questionnaire-15. Physical health indicators included haemoglobin level, body mass index and illness episodes. Generalised estimating equations were used to conduct hypothesis-driven and exploratory multivariable analyses in the panel at 2.5 and 3.5 years. RESULTS: The prevalence of maternal fatigue was 8.3% at 2.5 years and 5.5% at 3.5 years post-partum. Psychological symptoms of maternal CMD were associated independently with complaints of fatigue after adjusting for anaemia, body mass index, physical ill health, poverty and other confounding variables: adjusted odds ratio (aOR), 1.46; 95% confidence interval (CI), 1.28-1.66 for each one point increase in SRQ score. In the multivariable model, only psychosocial factors (CMD and stressful life events) and self-reported physical ill health were associated significantly with complaints of fatigue. CONCLUSION: Complaints of fatigue are associated strongly with maternal CMD and other psychosocial risk factors in this rural, low-income country setting with a high burden of undernutrition and infectious disease. Fatigue should be understood as a potential indicator of CMD in primary care to improve detection and treatment. PMID- 26683694 TI - Evaluation of an international faculty development program for developing countries in Asia: the Seoul Intensive Course for Medical Educators. AB - BACKGROUND: The issue of collaboration in medical education is becoming prominent. Some faculty development programs have suggested an approach for promoting collaboration on a global level. However, non-English-speaking developing countries in Asia, especially in Southeast Asia, do not take advantage of them due to their unique context, such as language and culture. To address these issues, Seoul National University College of Medicine initiated a 6-week international faculty development program called the "Seoul Intensive Course for Medical Educators" for 16 fellows from five Asian countries (Cambodia, Laos, Mongolia, Myanmar, and Vietnam). The aim of this study is to report the evaluation results of the outcome of the program and discuss better ways of collaborating with developing countries. METHODS: Three levels of collaboration intraorganizational, intranational, and international-were central initiatives of the program. Prior to setting up the program details, we first established four design principles, following which the contents, materials, and facilitators were determined to maintain consistency with the design principles. The evaluation of the program was done with Kirkpatrick's four-level model. Most of the evaluation data for level 1 were collected by two questionnaires, the post-module survey and the post-program survey. Portfolios and progress reports were mainly used to collect outcome data for levels 2 and 3, respectively. RESULTS: The reaction was generally positive throughout the program and there was a significant correlation between satisfaction and relevance to one's job or needs. Despite the fellows' propensity for overestimating themselves, both the evaluators and fellows reported that there was significant improvement in learning. Opinions on the impact or urgency of the topics were slightly different from country to country; however, the answers regarding feasibility were fairly similar. Moreover, we could observe from the post-program progress reports that the transfer of learning was actively in progress, mainly for topics that were highly feasible. CONCLUSIONS: These results show that the program was successful in terms of its effectiveness. Consistent and timely support is essential for the sustainable development of the medical education systems in these countries. Further understanding of the underlying factors on transfer (level 3) could improve the effectiveness of faculty development programs for developing countries. PMID- 26683695 TI - The Happy Older Latinos are Active (HOLA) health promotion and prevention study: study protocol for a pilot randomized controlled trial. AB - BACKGROUND: Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at risk Latinos. METHODS/DESIGN: HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). This prevention approach will be tested against a fotonovela, an enhanced psychoeducation control condition, in a sample of Latino elderly with minor or subthreshold depression or anxiety. A total of 60 older Latinos (aged 60+) will be randomized to receive HOLA or the fotonovela. The primary outcomes of interest are recruitment, adherence, retention, and acceptability. Data will also be collected on: preemption of incident and recurrent major depression, generalized anxiety, and social phobia; reduction in depression and anxiety symptom severity; physical functioning; sedentary behaviors; social engagement; and self-efficacy. DISCUSSION: The results of this study could have implications for other high risk, highly disadvantaged populations. The development of a health promotion intervention designed to prevent common mental disorders could be a means of addressing multiple disparities (for example, mental health outcomes, mental health service use, stigma) among racial/ethnic minority elderly. CLINICALTRIALS. GOV IDENTIFIER: NCT02371954 . Date of registration: 21 January 2015. PMID- 26683697 TI - Health-related physical fitness is associated with total and central body fat in preschool children aged 3 to 5 years. AB - OBJECTIVES: To investigate whether health-related physical fitness is associated with total and central body fat in preschool children. METHODS: A total of 403 Spanish children aged 3-5 years (57.8% boys) participated in the study. Health related physical fitness was measured by the PREFIT battery: the handgrip strength and the standing long-jump tests (muscular strength), the 4 * 10 m shuttle run (speed-agility), the one-leg stance tests (balance) and the PREFIT-20 m shuttle run test (cardiorespiratory fitness). Body mass index and waist circumference were used as markers of total and central body fat, respectively. RESULTS: There were significant associations between all health-related physical fitness tests and body mass index (beta = 0.280 +/- 0.054, beta = -0.020 +/- 0.006, beta = 0.154 +/- 0.065 and beta = -0.034 +/- 0.011 for the handgrip strength, standing long jump, 4 * 10 m shuttle run and PREFIT-20 m shuttle run tests, respectively, all P <= 0.019) after adjusting for sex and age. Similarly, there was significant associations of standing long jump (beta = -0.072 +/- 0.014), 4 * 10 m shuttle run (beta = 0.652 +/- 0.150) and PREFIT-20 m shuttle run tests (beta = -0.102 +/- 0.025) with waist circumference (all P <= 0.001), except for handgrip strength (beta = 0.254 +/- 0.145, P = 0.081) and one-leg stance (beta = -0.012 +/- 0.009, P = 0.156). CONCLUSIONS: The present study extends previous findings in older youth. Fitness assessment should be introduced in future epidemiological and intervention studies in preschool children because it seems to be an important factor determining health. PMID- 26683696 TI - EGFR/Ras Signaling Controls Drosophila Intestinal Stem Cell Proliferation via Capicua-Regulated Genes. AB - Epithelial renewal in the Drosophila intestine is orchestrated by Intestinal Stem Cells (ISCs). Following damage or stress the intestinal epithelium produces ligands that activate the epidermal growth factor receptor (EGFR) in ISCs. This promotes their growth and division and, thereby, epithelial regeneration. Here we demonstrate that the HMG-box transcriptional repressor, Capicua (Cic), mediates these functions of EGFR signaling. Depleting Cic in ISCs activated them for division, whereas overexpressed Cic inhibited ISC proliferation and midgut regeneration. Epistasis tests showed that Cic acted as an essential downstream effector of EGFR/Ras signaling, and immunofluorescence showed that Cic's nuclear localization was regulated by EGFR signaling. ISC-specific mRNA expression profiling and DNA binding mapping using DamID indicated that Cic represses cell proliferation via direct targets including string (Cdc25), Cyclin E, and the ETS domain transcription factors Ets21C and Pointed (pnt). pnt was required for ISC over-proliferation following Cic depletion, and ectopic pnt restored ISC proliferation even in the presence of overexpressed dominant-active Cic. These studies identify Cic, Pnt, and Ets21C as critical downstream effectors of EGFR signaling in Drosophila ISCs. PMID- 26683698 TI - Multi-walled carbon nanotubes change morpho-functional and GABA characteristics of mouse cortical astrocytes. AB - BACKGROUND: Multi-walled carbon nanotubes (MW-CNTs) have been extensively explored for their possible beneficial use in the nervous system. CNTs have shown to modulate neuronal growth and electrical properties, but its effect that varying length of MW-CNTs on primary astrocyte roles have not been clearly demonstrated yet. RESULTS: We investigate here the effect of MW-CNTs on astrocytic morphology, cell-cell interaction and the distribution of intracellular GABA (gamma-amino butyric acid). Primary cultured cortical astrocytes on MW-CNT-coated glass coverslips grow rounder and make more cell-cell interactions, with many cell processes, compared to astrocytes on poly-D-lysine (PDL) coverslips. In addition, intracellular GABA spreads into the cell processes of astrocytes on MW-CNT coverslips. When this GABA spreads into cell processes from the cell body GABA can be released more easily and in larger quantities compared to astrocytes on PDL coverslips. CONCLUSIONS: Our result confirm that MW CNTs modulate astrocytic morphology, the distribution of astrocytic GABA, cell cell interactions and the extension of cell processes. CNTs look to be a promising material for use neuroprosthetics such as brain-machine interface technologies. PMID- 26683700 TI - Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture. AB - Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. PMID- 26683699 TI - Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia. AB - Mutations of cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial ligand-gated anion channel, are associated with the lethal genetic disease cystic fibrosis. The CFTR G551D mutation impairs ATP hydrolysis and thereby makes CFTR refractory to cAMP stimulation. Both wild-type (WT) and G551D CFTR have been implicated in regulatory volume decrease (RVD), but the underlying mechanism remains incompletely understood. Here, we show that the channel activity of both WT and G551D CFTR is directly stimulated by mechanical perturbation induced by cell swelling at the single-channel, cellular, and tissue levels. Hypotonicity activated CFTR single channels in cell-attached membrane patches and WT-CFTR-mediated short-circuit current (Isc) in Calu-3 cells, and this was independent of Ca(2+)and cAMP/PKA signaling. Genetic suppression and ablation but not G551D mutation of CFTR suppressed the hypotonicity- and stretch inducedIscin Calu-3 cells and mouse duodena. Moreover, ablation but not G551D mutation of the CFTR gene inhibited the RVD of crypts isolated from mouse intestine; more importantly, CFTR-specific blockers markedly suppressed RVD in both WT- and G551D CFTR mice, demonstrating for the first time that the channel activity of both WT and G551D CFTR is required for epithelial RVD. Our findings uncover a previously unrecognized mechanism underlying CFTR involvement in epithelial RVD and suggest that the mechanosensitivity of G551D CFTR might underlie the mild phenotypes resulting from this mutation.-Xie, C., Cao, X., Chen, X, Wang, D., Zhang, W. K., Sun, Y., Hu, W., Zhou, Z., Wang, Y., Huang, P. Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia. PMID- 26683701 TI - Sleep and cardiometabolic risk in children and adolescents. AB - The evidence for a link between sleep and cardiometabolic risk factors in children and adolescents is accumulating; however, the literature has not yet been reviewed. Seventy-five studies investigating associations between sleep variables and measures of abdominal adiposity, glucose homeostasis, blood lipids, blood pressure (BP), and inflammatory markers were included in the present review. The current evidence indicates that inadequate sleep may play a role in cardiometabolic risk at a later age for children and adolescents. Most compelling is the evidence for an association between inadequate sleep and abdominal adiposity, decreased insulin sensitivity as well as high BP, whereas the evidence for potential links between sleep and blood lipids as well as inflammatory markers is less convincing. It should, however, be noted that the majority of studies linking sleep with cardiometabolic outcomes are cross-sectional in nature, and sleep is often assessed using parent or self-report. We suggest that future studies should investigate longitudinal associations between sleep and cardiometabolic risk factors with the use of objective sleep measurements conducted for several days, including weekdays and weekend days, at multiple time points over time. Meanwhile, based on the available evidence, we recommend that children and adolescents get adequate amounts of good sleep in a regular pattern. PMID- 26683702 TI - Illness trajectories in patients suffering from leg ulcers: A qualitative study. AB - The aim of this study was to identify illness trajectories in leg ulcers by analysing personal, social and relational dimensions related to leg ulcer onset and to the care process. Semi-structured interviews were conducted with 21 patients, one physician and four nurses. Patients' medical records were also examined. Data were analysed using the grounded theory approach. Four illness trajectories were identified: possibility, denial, focus on illness and tragedy. The findings highlighted that leg ulcers can be experienced in different ways depending on the personal characteristics of the people suffering from them and the kind of relationship that exists between patients and healthcare professionals. PMID- 26683703 TI - Posttraumatic stress disorder and exposure to trauma reminders after a terrorist attack. AB - The aims of this study were twofold: (a) to systematically describe the type and frequency of trauma reminders reported after a terrorist attack and (b) to examine whether posttraumatic stress disorder (PTSD) is associated with frequency of exposure to trauma reminders. A total of 285 survivors (M age = 22.2, SD = 4.3, 53% males) of the 2011 massacre on Utoya Island, Norway, were interviewed face to face 14-15 months after the terror. Participants were asked how often they had experienced a range of different trauma reminders in the past month and which was most distressing. Current posttraumatic stress reactions were measured using the University of California at Los Angeles PTSD Reaction Index. In all, 33.3% of the survivors reported having experienced 1 or more trauma reminders often/very often in the past month. Auditory reminders were most frequently encountered and were reported to be the most distressing, especially sudden and sharp noises. Meeting the diagnostic criteria for PTSD was significantly associated with frequency of exposure to trauma reminders. The findings suggest that trauma reminders are common among survivors of a terrorist attack almost 1.5 years after the trauma and that PTSD is strongly related to the frequency of exposure to reminders. It is important that clinicians are aware of the significant role trauma reminders may play in maintaining PTSD and help trauma survivors recognize and manage reminders. PMID- 26683704 TI - ucFabV Requires Functional Reductase Activity to Confer Reduced Triclosan Susceptibility in Escherichia coli. AB - BACKGROUND/AIMS: We previously identified the Triclo1 fosmid in a functional metagenomic selection for clones that increased triclosan tolerance in Escherichia coli. The active enzyme encoded by Triclo1 is ucFabV. Although ucFabV is homologous to FabV from other organisms, ucFabV contains substitutions at key positions that would predict differences in substrate binding. Therefore, a detailed characterization of ucFabV was conducted to link its biochemical activity to its ability to confer reduced triclosan sensitivity. METHODS: ucFabV and a catalytic mutant were purified and used to reduce crotonoyl-CoA in vitro. The mutant and wild-type enzymes were introduced into E. coli, and their ability to confer triclosan tolerance as well as suppress a temperature-sensitive mutant of FabI were measured. RESULTS: Purified ucFabV, but not the mutant, reduced crotonoyl-CoA in vitro. The wild-type enzyme confers increased triclosan tolerance when introduced into E. coli, whereas the mutant remained susceptible to triclosan. Additionally, wild-type ucFabV, but not the mutant, functionally replaced FabI within living cells. CONCLUSION: ucFabV confers increased tolerance through its function as an enoyl-ACP reductase. Furthermore, ucFabV is capable of restoring viability in the presence of compromised FabI, suggesting ucFabV is likely facilitating an alternate step within fatty acid synthesis, bypassing FabI inhibition. PMID- 26683705 TI - miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis. AB - Mesenchymal Stromal/Stem Cells (MSC) are currently being explored in diverse clinical applications, including regenerative therapies. Their contribution to regeneration of bone fractures is dependent on their capacity to proliferate, undergo osteogenesis and induce angiogenesis. This study aimed to uncover microRNAs capable of concomitantly regulate these mechanisms. Following microRNA array results, we identified miR-195 and miR-497 as downregulated in human primary MSC under osteogenic differentiation. Overexpression of miR-195 or miR 497 in human primary MSC leads to a decrease in osteogenic differentiation and proliferation rate. Conversely, inhibition of miR-195 increased alkaline phosphatase expression and activity and cells proliferation. Then, miR-195 was used to study MSC capacity to recruit blood vessels in vivo. We provide evidence that the paracrine effect of MSC on angiogenesis is diminishedwhen cells over express miR-195. VEGF may partially mediate this effect, as its expression and secreted protein levels are reduced by miR-195, while increased by anti-miR-195, in human MSC. Luciferase reporter assays revealed a direct interaction between miR-195 and VEGF 3'-UTR in bone cancer cells. In conclusion, our results suggest that miR-195 regulates important mechanisms for bone regeneration, specifically MSC osteogenic differentiation, proliferation and control of angiogenesis; therefore, it is a potential target for clinical bone regenerative therapies. PMID- 26683706 TI - A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis. AB - As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury. PMID- 26683707 TI - Toxic effect of NiCl2 on development of the bursa of Fabricius in broiler chickens. AB - This study was conducted with objective of evaluating the toxic effects of nickel chloride (NiCl2) on development of bursa of Fabricius in broilers fed on diets supplemented with 0, 300, 600 and 900 mg/kg of NiCl2 for 42 days by using the methods of experimental pathology, flow cytometry (FCM), and quantitative real time polymerase chain reaction (qRT-PCR). The results showed that dietary NiCl2 in 300 mg/kg and over induced toxic suppression in the bursal development, which was characterized by decreasing lymphocytes histopathologically and relative weight, increasing G0/G1 phase (a prolonged nondividing state), reducing S phase (DNA replication) and proliferating index, and increasing percentages of apoptotic cells. Concurrently, the mRNA expression levels of bax, cytochrome c (cyt c), apoptotic peptidase activating factor 1 (Apaf-1), caspase-3, caspase-6, caspase-7 and caspase-9 were increased and the bcl-2 mRNA expression levels were decreased. The toxic suppression of bursal development finally impaired humoral immunity duo to the reduction of B lymphocyte population and B lymphocyte activity in the broiler chicken. This study provides new evidences for further studying the effect mechanism of Ni and Ni compoundson B-cell or bursa of Fabricius. PMID- 26683708 TI - Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia. AB - Streptococcus pneumoniae is responsible for significant mortality and morbidity worldwide and causes invasive pneumococcal diseases including pneumococcal meningitis. Pyroptosis is caspase-1-dependent inflammatory cell death and is known to be induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by S. pneumoniae in microglia. Our results revealed that S. pneumoniae induced pyroptosis through caspase-1 activation and IL-1beta production. We also found that the activation of caspase-1 and the maturation of IL-1beta and IL-18 in the S. pneumoniae-triggered pyroptotic cell death process were mediated by NLRP3 inflammasome. In addition, pneumococcal infection increased the expression of autophagy-related genes and induced autophagosome formation. We also showed that the inhibition of autophagy promoted pneumococcus-induced pyroptosis. Furthermore, ROS was generated by pneumococcal infection and inhibited caspase-1 activation within 4 h of infection. However, in the late phase of infection, IL 1beta secretion and caspase-1-dependent cell death were induced by ROS. These results suggest that autophagy induction transiently delay pyroptosis induced by S. pneumoniae in microglia. Our study also revealed that the activation of caspase-1 and the production of IL-1beta were induced by pneumolysin and that pneumolysin triggered pyroptosis in microglial cells. Similar to the in vitro results, S. pneumoniae induced caspase-1 activation and caspase-1-dependent cytokine maturation in the mouse meningitis model. Thus, the present data demonstrate that S. pneumoniae induces pyroptosis in murine microglia and that NLRP3 inflammasome is critical for caspase-1 activation during the process. Furthermore, the induction of autophagy could transiently protect microglia from pyroptosis. PMID- 26683710 TI - Glandular dose in breast computed tomography with synchrotron radiation. AB - The purpose of this work is to provide an evaluation of the mean glandular dose (MGD) for breast computed tomography (CT) with synchrotron radiation in an axial scanning configuration with a partial or total organ volume irradiation, for the in vivo program of breast CT ongoing at the ELETTRA facility (Trieste, Italy). A Geant4 Monte Carlo code was implemented, simulating the photon irradiation from a synchrotron radiation source in the energetic range from 8 to 50 keV with 1 keV intervals, to evaluate the MGD. The code was validated with literature data, in terms of mammographic normalized glandular dose coefficients (DgN) and with ad hoc experimental data, in terms of computed tomography dose index (CTDI). Simulated cylindrical phantoms of different sizes (diameter at phantom base 8, 10, 12, 14 or 16 cm, axial length 1.5 times the radius) and glandular fraction by weight (0%, 14.3%, 25%, 50%, 75% and 100%) were implemented into the code. The validation of the code shows an excellent agreement both with previously published work and in terms of DgN and CDTI measurements. The implemented simulations show a dependence of the glandular dose estimate on the vertical dimension of the irradiated zone when a partial organ irradiation was implemented. Specific normalized coefficients for calculating the MGD to the whole breast or to the single irradiated slice were reported. PMID- 26683709 TI - Prognostic value of high EZH2 expression in patients with different types of cancer: a systematic review with meta-analysis. AB - Enhancer of zeste homologue 2 (EZH2) is a potential independent mechanism for epigenetic silencing of tumor suppressor genes in cancer. We conducted an electronic search on PubMed, EMBASE, Web of Science, and Cochrane library to perform this up-to-date meta-analysis. Fifty-one studies with a total of 9444 patients were included. The prevalence of high EZH2 expression was 0.54 (95% CI: 0.47-0.61). High EZH2 expression was significantly associated with poorer prognosis [overall survival: HR 1.54 (95% CI: 1.30-1.78), P < 0.000; disease free survival: HR 1.35 (95% CI: 1.00-1.71), P < 0.000]. In breast cancer, high EZH2 expression correlated with histological types [OR: 1.53 (95CI: 1.13-2.06); P < 0.006], histological grade [OR: 1.62 (95CI: 1.35-1.95); P < 0.000], estrogen receptor (ER) negativity [OR: 2.05 (95CI: 1.67-2.52); P < 0.000], progesterone receptor (PgR) negativity [OR: 1.42 (95CI: 1.03-1.96); P = 0.034], HER-2 positivity [OR: 1.35 (95CI: 1.08-1.69); P = 0.009], and high p53 expression [OR: 1.66 (95CI: 1.07-2.59); P = 0.024]. These results suggest that high EZH2 expression may be a promising prognostic factor to different cancers. High EZH2 expression tends to correlate with pathological types, histological grade, ER negativity, PgR negativity, HER-2 positivity and p53 high expression in breast cancer. PMID- 26683711 TI - Nursing and midwifery: Pillars of rural and remote health innovation and development. PMID- 26683712 TI - Promoting the uptake of preventative Aboriginal child health policy in Western Australia. AB - PROBLEM: Australian Aboriginal children are over-represented on all negative health indicators compared with non-Aboriginal children.Contributing factors to the disparity include the impact of historical events, racism and social determinants of health. Despite the benefits of child health checks, offered through the Medicare Benefit Schedule and community health services, uptake of these is low. DESIGN: In 2012, Western Australia Health implemented the Enhanced Aboriginal Child Health Schedule (EACHS) policy to address specific health needs of Aboriginal children. The Aboriginal Child Heath Project (the Project), was a five-year initiative funded through the Council of Australian Governments. Project staff promoted the profile of preventative child health and the uptake of the EACHS policy across the state by agencies operating in the sector. SETTING: Western Australia. KEY MEASUREMENTS FOR IMPROVEMENT: Reach of the implementation workshop was measured by the number of staff attending policy implementation and the total number for agencies represented. One measure of impact was the number of agencies requesting the EACHS policy who adapted or adopted it to deliver evidence based comprehensive child health programs. STRATEGIES FOR CHANGE: The Project offered policy implementation workshops to health staff delivering services to young Aboriginal children. In addition to the evidence-based policy, a suite of resources were made available to support service delivery. EFFECTS OF CHANGE: The EACHS is a framework used by agencies to deliver consistent care and support governance when providing child health services to Aboriginal families across Western Australia. LESSONS LEARNT: Providing a policy that was consistent with identified service strengths allowed agencies to individually build their capacity to deliver child health checks, using existing resources, at their own pace. PMID- 26683713 TI - Chronic kidney disease in an Aboriginal population: A nurse practitioner-led approach to management. AB - PROBLEM: Chronic kidney disease (CKD) is a significant health problem impacting Australia's Aboriginal and Torres Strait Islander population. After age adjustment, the prevalence of kidney disease is 3.7 times higher in Aboriginal people and 7.3 times higher for end-stage kidney disease compared with the wider population. Yet at an Aboriginal Community Controlled Health Service (ACCHS) with a significant patient population, fewer than expected numbers of Aboriginal patients were identified with CKD. DESIGN: The ACCHS engaged a nurse practitioner to lead a systematic approach to the identification and treatment of CKD. SETTING: This nurse practitioner-led approach to CKD was developed and implemented at a rural NSW ACCHS, with the support of a partnership formed between the nurse practitioner, the ACCHS, a nephrologist from a referral hospital and a statewide NGO. KEY MEASURES FOR IMPROVEMENT: The primary measure for improvement has been to identify and stage patients with CKD and establish management plans as appropriate. STRATEGIES FOR CHANGE: This nurse-led project was established to: (i) identify patients with CKD; (ii) provide access for CKD patients to appropriate services; (iii) commence pharmacological and non pharmacological strategies that enable remission or regression of CKD; and (iv) educate practice GPs and other staff members on CKD clinical guidelines and best practice. EFFECTS OF CHANGE: The CKD project has improved access to essential health care for vulnerable and at-risk populations, with 187 patients to date having been identified with kidney disease and staged for its severity. LESSONS LEARNT: The need for strong multi-disciplinary teamwork has been demonstrated with good communication strategies implemented. PMID- 26683714 TI - Promoting women's health in remote Aboriginal settings: Midwifery students' insights for practice. AB - OBJECTIVE: To describe midwifery students' insights on promoting health to Aboriginal women in remote Australia following a supervised clinical placement. DESIGN: Semistructured, in-depth interviews were conducted with all midwifery students who undertook the placement between 2010 and 2013. SETTING: Aboriginal communities on the Ngaanyatjarra Lands, Western Australia. PARTICIPANTS: Undergraduate and postgraduate midwifery students from a Western Australian university. INTERVENTIONS: Remote cultural immersion clinical placement. MAIN OUTCOME MEASURES: Student learning related to culturally respectful health care delivery and promotion of health. RESULTS: Students observed that, despite vast distances, high rates of participation in a breast screening program were achieved due to the informal provision of culturally relevant information and support. Opportunistic encounters in communities also enabled sexual health messages to be delivered more widely and in less formal settings. The role played by Aboriginal Health Workers and female family members was vital. The importance of culturally respectful approaches to sensitive women's business, including discretion, the use of local language and pictorial representations of information, was recognised as was the socio-cultural context and its impact on the health and well-being of the community. CONCLUSIONS: Although short in duration, the Ngaanyatjarra Lands clinical placement provided midwifery students with a rare opportunity to observe the importance of local contexts and cultural protocols in Aboriginal communities, and to adapt health promotion strategies to meet local needs and ways of doing things. These strategies embraced the strengths, assets and capacities of communities, yet students also witnessed challenges associated with access, delivery and acceptance of health care in remote settings. PMID- 26683715 TI - Birthing in rural South Australia: The changing landscape over 20 years. AB - OBJECTIVE: To map trends in the maternity service availability for rural women in South Australia and identify the frequency of women birthing outside of their region of residence. DESIGN: A retrospective review of birth location for rural South Australian women from 1991 to 2010. SETTING: Rural maternity units in South Australia. PARTICIPANTS: Birthing statistics from the Pregnancy Outcomes Statistics Unit in South Australia MAIN OUTCOME MEASURES: Rural birth statistics, including place of birth in relation to place of residence and location of maternity units. RESULTS: Over 60% of maternity units across rural South Australia have closed since 1991. There has been a rise in the percentage of women birthing away from their usual region of residence, rising from 18% in 1991 1995 to 24% in 2006-2010. CONCLUSIONS: This study has revealed that almost one quarter of all women residing in rural South Australia relocate to another area to give birth. This is a significant concern for rural women and their families through the expectation of separation, and for the local health services who might now not have the facilities and skills to manage an unplanned maternity presentation. These concerns need to be considered and addressed in order to provide safe and effective care for child-bearing women regardless of location. PMID- 26683716 TI - Continuity of midwifery care for rural women through caseload group practice: Delivering for almost 20 years. AB - OBJECTIVE: To describe the clinical outcomes and sustainability factors of a long standing midwifery led caseload model of rural maternity care. DESIGN: Retrospective clinical audit from 1998 to 2011 and autoethnographic narrative of the midwifery program told by the longest serving midwives under three key themes relating to sustainable practice. SETTING: Regional Health Service with annual birth rate of 500. Maternity care is provided by either public antenatal clinic/GP shared care or midwife-led care. PARTICIPANTS: Women attending a rural caseload midwifery group practice between the period 1998-2011 and midwives working in the same group practice during that period. MAIN OUTCOME MEASURES: Antenatal attendance, maternal mortality, infant morbidity and mortality, mode of birth, known midwife at birth, initiation of breastfeeding. RESULTS: There were 1674 births between 1998 and 2011. Clinical outcomes for women and infants closely reflected national maternity indicator data. The group practice midwives attribute sustainability of the program to the enjoyment of flexibility in their working environment, to establishing trust amongst themselves, the women they care for, and with the obstetricians, GPs and health service executives. The rigorous application of midwifery principles including robust clinical governance have been hallmarks of success. CONCLUSION: This caseload midwifery group practice is a safe, satisfying and sustainable model of maternity care in a rural setting. Clinical outcomes are similar to standard care. Success can be attributed to strong leadership across all levels of policy, health service management and, most importantly, the rural midwives providing the service. PMID- 26683717 TI - Aged-care nurses in rural Tasmanian clinical settings more likely to think hypothetical medication error would be reported and disclosed compared to hospital and community nurses. AB - OBJECTIVE: This study aims to determine the likelihood that rural nurses perceive a hypothetical medication error would be reported in their workplace. DESIGN: This employs cross-sectional survey using hypothetical error scenario with varying levels of harm. SETTING: Clinical settings in rural Tasmania. PARTICIPANTS: Participants were 116 eligible surveys received from registered and enrolled nurses. MAIN OUTCOME MEASURES: Frequency of responses indicating the likelihood that severe, moderate and near miss (no harm) scenario would 'always' be reported or disclosed. RESULTS: Eighty per cent of nurses viewed a severe error would 'always' be reported, 64.8% a moderate error and 45.7% a near-miss error. In regards to disclosure, 54.7% felt this was 'always' likely to occur for a severe error, 44.8% for a moderate error and 26.4% for a near miss. Across all levels of severity, aged-care nurses were more likely than nurses in other settings to view error to 'always' be reported (ranging from 72-96%, P = 0.010 to 0.042,) and disclosed (68-88%, P = 0.000). Those in a management role were more likely to view error to 'always' be disclosed compared to those in a clinical role (50-77.3%, P = 0.008-0.024). CONCLUSION: Further research in rural clinical settings is needed to improve the understanding of error management and disclosure. PMID- 26683718 TI - Face to face, person to person: Skills and attributes deployed by rural mental health clinicians when engaging with consumers. AB - OBJECTIVE: The purpose of this study was to identify the skills and attributes deployed by rural mental health clinicians when engaging with consumers in the community mental health context. DESIGN: Reflecting the exploratory nature of this research, a semi-structured focus group was conducted. SETTING: One community mental health service in regional South Australia (catchment area = approximately 60 000 people). PARTICIPANTS: Nine mental health clinicians. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants' focus group comments were explored qualitatively using thematic analysis. RESULTS: Three major themes were identified: (i) limitations to providing mental health care in the rural environment (increased consumer vulnerability, limited services, increased risk, and stigma); (ii) universal engagement approaches (being consumer focused, appropriate communication, facilitating a connection and normalising the experience); (iii) indicated and targeted strategies for engagement (flexible and creative delivery of care, a whole of community approach, being multiskilled and technology use). CONCLUSIONS: Although engaging with consumers involves many skills and attributes employed universally across mental health settings, the rural clinician's ability to navigate the environment and utilise this to provide consumer care is equally important to the engagement process. Specifically, these findings highlight the preference of rural mental health clinicians towards a person-centred approach, networking with others in the community when providing care. Understanding how best to maximise the nature of a rural environment, such as facilitating relationships between clinicians and others in the community, will contribute to optimised care. PMID- 26683719 TI - Work and personal well-being of nurses in Queensland: Does rurality make a difference? AB - OBJECTIVE: This study aims to ascertain if differences exist in the perception of the professional practice environment and personal well-being of nurses across different geographical areas in Queensland. DESIGN: This paper was performed on a prospective, self-report cross-sectional on-line survey. SETTING: The study was conducted among the nurses employed in public and private health care settings: acute hospitals, community health and aged care in Queensland, Australia. PARTICIPANTS: Participants of this study were 1608 registered and enrolled nurses and assistants in nursing, current members of the Queensland Nurses Union in 2013 and who provided a workplace postcode. One thousand eight of these participants worked in major cities, while 382 in rural locations and 238 in remote areas. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Scores of well-being as determined by the following scales: the Depression, Anxiety and Stress Scale, the Professional Quality of Life Scale version 5, the Connor-Davidson Resilience Scale and of the Professional Practice Environment using the Practice Environment Scale - Nursing Work Index Revised. RESULTS: Nurses employed in major cities perceived 'nursing foundations for quality care' more favourably than those from other settings. Remote area nurses had lower levels of secondary traumatic stress than nurses in major cities and rural areas. There was no difference between nurses across their geographical locations for stress, anxiety, depression, compassion satisfaction, burnout, resilience and the four other measures of the Practice Environment Scale. CONCLUSIONS: The study findings provide new data suggesting that, with the exception of secondary traumatic stress, the personal well-being of nurses does not differ across geographical settings. Similarly, with the exception of the subscale of 'nursing foundations for quality care' there was no difference in perceptions of the professional practice environment. As secondary traumatic stress is associated with burnout, this finding needs to be investigated further. PMID- 26683720 TI - Losing the rural nursing workforce: Lessons learnt from resigning nurses. AB - BACKGROUND: Australian workforce planning predicts a shortfall of nurses by 2025 with rural areas being most at risk. Rural areas have lower retention rates of nurses than metropolitan areas, with remote communities experiencing an even higher turnover of nursing staff. There have been few studies that examine the impact of nurse resignations on rural nursing workforces. OBJECTIVE: This paper is abstracted from a larger study into the reasons why nurses resign from rural hospitals and explores the resignation period. DESIGN: A qualitative study using grounded theory methods. Following in-depth interviewing and transcription, data analysis occurred with the assistance of NVivo software. SETTING: Rural NSW. PARTICIPANTS: Twelve registered nurses who had resigned from rural NSW hospitals and not for reasons of retirement, maternity leave or relocation; two participants were re-interviewed. RESULTS: While the overall study identified a grounded theory which explained rural nurses resign from hospitals due to a conflict of values, three additional themes emerged about the resignation practices at rural hospitals. The first theme identified a 'window period' which was an opportunity for the nurse to be retained. The second theme identified that nurses who had resigned were not involved in formal exit processes such as exit interviews. The third theme captured the flow-on effect from rural nurse resignations resulting in nurses leaving the profession of nursing. CONCLUSION: To facilitate nurse retention, it is important that rural hospitals manage nurse resignations more effectively. This includes re-examining resignation procedures, how nurses are treated and collecting meaningful data to inform retention strategies. PMID- 26683722 TI - From Reduction to Apocope: Final Poststressed Vowel Devoicing in Brazilian Portuguese. AB - This is a study of final poststressed vowel devoicing following /s/ in Brazilian Portuguese. We contradict the literature describing it as deletion by arguing, first, that the vowel is not deleted, but overlapped and devoiced by the /s/, and, second, that gradient reduction with devoicing may lead to apocope diachronically. The following results support our view: (1) partially devoiced vowels are centralized; (2) centralization is inversely proportional to duration; (3) total devoicing is accompanied by lowering of the /s/ centroid; (4) the /s/ noise seems to be lengthened when the vowel is totally devoiced; (5) aerodynamic tests reveal that lengthened /s/ has a final vowel-like portion, too short to be voiced; (6) lengthened /s/ favors vowel recovery in perceptual tests. This seems to be a likely path from reduction to devoicing to listener-based apocope. PMID- 26683738 TI - Different Medications for Hypogonadotropic Hypogonadism. AB - Delayed puberty (DP) in boys is the lack of sexual maturation at a chronological age of 14 years. Several conditions induce DP and they can be classified into reversible and irreversible causes. The most common cause of DP is constitutional delay of puberty (CDP; 63%), followed by DPs due to functional hypogonadotropic hypogonadism (HH; 20%), congenital isolated HH (9%) and hypergonadotropic hypogonadism (7%). A correct diagnosis, although often difficult, is pivotal for choosing the most adequate therapy. In CDP boys, expectant management can be an option. However, patient's psychological distress can be attenuated by short-term low-dose testosterone therapy, which can induce male secondary sexual characteristics. When therapy is discontinued in CDP, pubertal development continues similarly to normal boys. Long-term testosterone therapy is the only option in boys with DP due to hypergonadotropic hypogonadism, whereas in subjects with HH, besides long-term testosterone, also gonadotropins and gonadotropin releasing hormone (GnRH) can be used. Gonadotropins and GnRH, besides inducing secondary sexual characteristics, can also induce testicular maturation and spermatogenesis. Other molecules, such as kisspeptin and neurokinin B agonists, are now under evaluation as new therapeutic options for treating DP. PMID- 26683739 TI - X-linked recessive VACTERL-H due to a mutation in FANCB in a preterm boy. PMID- 26683740 TI - Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model. AB - Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid formation and essential dermal/epidermal interactions in disease development, the novel animal model was established by implanting porous polyethylene ring-supported plasma/fibrin-based epidermal-dermal skin constructs on the dorsum of athymic NU/J mice. The implants were stable to 18 weeks, contained abundant human cells, and remodeled to yield scar architecture characteristic of keloid fibrosis compared with normal implants and clinical specimens: (1) macroscopic convex or nodular scar morphology; (2) morphogenesis and accumulation of large collagen bundles from collagen-null initial constructs; (3) epidermal hyperplasia, aberrant epidermal-dermal patency, and features of EMT; (4) increased vasculature, macrophage influx, and aggregation; and (5) temporal-spatial increased collagen-inducing PAI-1 and its interactive partner uPAR expression. Development of such pathology in the NU/J host suggests that T-cell participation is less important at this stage than at keloid initiation. These accessible implants also healed secondary excisional wounds, enabling clinically relevant contemporaneous wounding and treatment strategies, and evaluation. The model provides a robust platform for studying keloid formation and testing knowledge based therapies. PMID- 26683742 TI - Solubility Switching of Metallophthalocyanines and Their Larger Derivatives upon Encapsulation. AB - Metallophthalocyanines (MPcs) are very useful pigments but scarcely soluble without appropriate functional groups in common solvents. Herein, we report that bent polyaromatic amphiphiles act as excellent solubilizing reagents for nonfunctionalized MPcs and larger MPc derivatives (e.g., CuPc, perhalogenated CuPcs, Cu-naphthalocyanine, CuPc polymers, and double-decker MPcs) in neutral water upon encapsulation. The resultant MPc nanocomposites display high stability towards heat and pH change. More importantly, the encapsulated MPcs can be released by simple protocols under mild conditions both into a bulk solvent and onto glass or polymer plates. PMID- 26683741 TI - Analysis of Risk of Recurrence by Subtype in <= 1-cm Breast Tumors. AB - INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher recurrence rates than other breast cancer subtypes. Increasing numbers of women are being diagnosed with early-stage breast cancer because of improvements in screening mammography. TNBC is known to be highly sensitive to chemotherapy; however, the benefit of adjuvant chemotherapy among women with <= 1-cm, lymph node-negative TNBC is unknown. MATERIALS AND METHODS: We evaluated the recurrence rates and recurrence-free survival of 437 women diagnosed with stage T1a-T1bN0 breast cancer from 1997 to 2009 at 2 institutions, with a median follow-up time of 6.2 years. Furthermore, we examined the treatment regimens of these women and evaluated the association of adjuvant chemotherapy with recurrence-free survival. RESULTS: Chemotherapy was administered more often to younger women and to women with high-grade, human epidermal growth factor receptor 2-positive or TNBC. Recurrence-free survival did not differ significantly between TNBC and estrogen receptor-positive breast cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.04; P = .058). After appropriate adjustments, no significant differences were detected in recurrence free survival between the women who had received chemotherapy and those who had not among the women with TNBC (P = .132) or within any of the breast cancer subtypes (HR, 0.6; 95% CI, 0.2-1.9; P = .392). CONCLUSION: Prospective trials of this subcentimeter node-negative breast cancer population are warranted to guide adjuvant chemotherapy decisions. PMID- 26683743 TI - How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors. AB - BACKGROUND: Nocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone. OBJECTIVES: To quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores. METHODS: Nocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy. RESULTS: PD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed. CONCLUSION: Our study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms. PMID- 26683744 TI - Neuroimaging and clinical predictors of fatigue in Parkinson disease. AB - BACKGROUND: Fatigue is disabling in Parkinson disease. It is often associated with other non-motor symptoms, but little is known about its underlying pathophysiology. OBJECTIVE: To investigate neuroimaging (using dopaminergic and cholinergic PET) and clinical factors associated with fatigue severity in PD. METHODS: 133 PD subjects (96M/37F) completed the Fatigue Severity Scale, Movement Disorders Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS), Hoehn-Yahr staging, validated scales for depression, anxiety, apathy, sleep, and cognition, and underwent [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [(11)C]dihydrotetrabenazine (DTBZ) monoaminergic PET imaging. We explored contributions to PD fatigue using separate regression models based either on neuroimaging parameters or clinicometric scales. RESULTS: In a neuroimaging regression model, neither striatal DTBZ uptake nor AChE PMP uptake were predictors of fatigue in PD. In a post-hoc neuroimaging regression model, stratifying the total cohort into mild vs. moderate-to-severe PD, striatal DTBZ uptake was a significant predictor of fatigue in mild but not moderate-to severe PD. In a clinicometric regression model, higher Beck Depression Inventory somatic subscore, higher levodopa dose equivalents and younger age were all significant predictors of fatigue in PD, but the MDS-UPDRS non-motor experiences of daily living score was the best predictor overall. CONCLUSIONS: Cholinergic uptake was not a predictor of fatigue in PD, but nigrostriatal dopaminergic denervation predicted fatigue in mild disease. Total non-motor symptom burden, somatic affective symptoms, levodopa dose equivalents, and younger age were independent clinical predictors of fatigue. PMID- 26683745 TI - Are factors related to dual-task performance in people with Parkinson's disease dependent on the type of dual task? AB - BACKGROUND: Impaired dual-task performance significantly impacts upon functional mobility in people with Parkinson's disease (PD). The aim of this study was to identify determinants of dual-task performance in people with PD in three different dual tasks to assess their possible task-dependency. METHODS: We recruited 121 home-dwelling patients with PD (mean age 65.93 years; mean disease duration 8.67 years) whom we subjected to regular walking (control condition) and to three dual-task conditions: walking combined with a backwards Digit Span task, an auditory Stroop task and a Mobile Phone task. We measured dual-task gait velocity using the GAITRite mat and dual-task reaction times and errors on the concurrent tasks as outcomes. Motor, cognitive and descriptive variables which correlated to dual-task performance (p < 0.20) were entered into a stepwise forward multiple linear regression model. RESULTS: Single-task gait velocity and executive function, tested by the alternating intake test, was significantly associated with gait velocity during the Digit Span (R(2) = 0.65; p < 0.001), the Stroop (R(2) = 0.73; p < 0.001) and the Mobile Phone task (R(2) = 0.62; p < 0.001). In addition, disease severity proved correlated to gait velocity during the Stroop task. Age was a surplus determinant of gait velocity while using a mobile phone. CONCLUSION: Single-task gait velocity and executive function as measured by a verbal fluency switching task were independent determinants of dual task gait performance in people with PD. In contrast to expectation, these factors were the same across different tasks, supporting the robustness of the findings. Future study needs to determine whether these factors predict dual-task abnormalities prospectively. PMID- 26683746 TI - Governing drug use through partnerships: Towards a genealogy of government/non government relations in drug policy. AB - Drug policy in Australia is underpinned by the idea of partnerships wherein the non-government sector is one important partner in both delivering services and contributing to policy and decision-making processes. This article presents a genealogy of the concept of government/non-government 'partnerships', tracing its emergence and development within drug policy discourse in Australia. We find that the rise of neo-liberal policies since the 1980s has been a key factor facilitating the emergence of government/non-government 'partnerships' rhetoric in drug policy. Since the 1980s, the role of non-government organisations (NGOs) in drug policy has been articulated in relation to 'community' responsibilisation in contrast to the welfarist reliance on expert intervention. We link the rise of this rhetoric with the neo-liberal turn to governing through community and the individualisation of social problems. Furthermore, although we find that governments on the whole have encouraged the service delivery and policy work of NGOs at least in policy rhetoric, the actions of the state have at times limited the ability of NGOs to perform advocacy work and contribute to policy. Constraints on NGO drug policy work could potentially compromise the responsiveness of drug policy systems by limiting opportunities for innovative policy-making and service delivery. PMID- 26683747 TI - Is There Any Relation Between the Degree of Fatty Liver Disease and Severity of Lower Urinary Tract Symptoms? AB - OBJECTIVE: To evaluate the association between the degree of fatty liver disease and severity of lower urinary tract symptoms (LUTS) in healthy middle-aged males. MATERIALS AND METHODS: A total of 1943 Korean men aged between 40 and 70 years who had participated in the voluntary health checkup program from January 2012 to December 2014 were enrolled. LUTS were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Abdominal ultrasonography was performed to assess nonalcoholic fatty liver disease (NAFLD). Trend test was performed to investigate the association between the degree of fatty liver disease and LUTS severity. Differences between the two groups were analyzed by chi-square test, and we adjusted for confounding factors with analysis of covariance and logistic regression test. RESULTS: The mean age was 51.79 +/- 7.03 years, and 1026 (52.8%) subjects were determined to have NAFLD. Differences in categorical variables, between NAFLD grades and IPSS grades, were analyzed by Trend test, and no significant difference was observed (Pearson chi-square, P = .155; likelihood ratio, P = .151; linear-by-linear association, P = .527). After adjustment for age, body mass index, metabolic syndrome, C-reactive protein, prostate specific antigen, prostate volume with analysis of covariance, and multiple logistic regression test, no significant associations were found between IPSS and NAFLD. CONCLUSION: No significant associations were found between NAFLD and LUTS in middle-aged men, and the degree of NAFLD was not significantly associated with the severity of LUTS in trend. The role of NAFLD, in comparison with age, might be too small to change the LUTS. PMID- 26683748 TI - Increased Body Mass Index in Men With Varicocele Is Associated With Larger Spermatic Vein Diameters When Supine. AB - OBJECTIVE: To evaluate the association of body mass index (BMI) and spermatic vein diameters (SVDs) in men treated for varicocele. SUBJECTS AND METHODS: One hundred fourteen men who underwent scrotal color duplex ultrasounds prior to microsurgical varicocelectomy were classified as normal (BMI = 18.5-24.9), overweight (25-29.9), or obese (>=30). SVDs were measured with and without Valsalva, standing and supine. SVD, pre- and postoperative semen analyses (SA) were compared. RESULTS: Forty-six (40.4%) men had normal BMI, 54 (47.3%) were overweight, and 14 (12.3%) were obese. Higher BMI was associated with smaller left testis volume and larger left SVD when supine (with and without Valsalva). The association was absent when standing. Men with higher BMI had smaller differences between their left SVD Valsalva diameters when standing vs supine. There were no differences among BMI classes for right SVD measurements, preoperative SA, and postoperative SA improvement. CONCLUSION: Increased BMI is associated with larger left SVD while supine, suggesting that increased abdominal pressure while recumbent may contribute to varicocele pathology in this population. Interestingly, as in the general population, a majority of the men were overweight. PMID- 26683749 TI - Reply by the Authors. PMID- 26683750 TI - Controversies and Advances With Testosterone Therapy: A 40-Year Perspective. AB - Testosterone therapy (TTh) has become highly controversial. There are important health consequences of testosterone deficiency, and meaningful benefits with treatment. There is level 1 evidence that TTh improves sexual function and desire, body composition, and bone density. Concerns regarding cardiovascular risk were based on two deeply flawed retrospective studies and are contradicted by dozens of studies showing cardiovascular benefits of TTh or higher endogenous testosterone, including placebo-controlled studies in men with known heart disease (angina, heart failure). Prostate cancer should no longer be considered a risk of TTh. Testosterone is neither scourge nor panacea--it is just good medicine. PMID- 26683751 TI - Preoperative Favorable Characteristics in Bladder Cancer Patients Cannot Substitute the Necessity of Extended Lymphadenectomy During Radical Cystectomy: A Sensitivity Curve Analysis. AB - OBJECTIVE: To investigate the staging of lymphadenectomy during radical cystectomy (RC) due to bladder cancer. No data exist about the possibility to limit the extension of pelvic lymph node dissection (PLND) on the basis of preoperative or intraoperative parameters without losing accuracy in the staging procedure. MATERIALS AND METHODS: Between 1995 and 2012, 1016 RC due to bladder cancer were performed at a single tertiary care institution. The relationship between the number of nodes removed and the probability to find node metastases at final pathology examination was assessed using receiver operating characteristic analyses. RESULTS: Among the patients who underwent RC plus PLND, the lymph node metastases prevalence was 35.7% (363 of 1016). Receiver operating characteristic curve analyses were used to explore graphically the relationship between the numbers of removed and examined nodes and the probability of finding one or more metastatic nodes in the overall population. The curve indicated that 25, 35, and 45 nodes need to be removed to achieve 75%, 90%, and 95% probability, respectively, of detecting one or more lymph node metastases. When the analyses were stratified according to preoperative characteristics, only slight differences were recorded among the sensitivity analyses stratified for pathological stage, primary or progressive status, or radiological N status. CONCLUSION: Our results show that it is necessary to extend PLND to improve the ability to stage node metastases accurately. Preoperative parameters can minimally change this indication and an extended PLND should be always performed. PMID- 26683752 TI - Laparoscopic Varicocelectomy in Adolescents: Artery Ligation and Artery Preservation. AB - OBJECTIVE: To evaluate and compare the perioperative outcomes and improvements of testicular performance between artery preservation (AP) and artery ligation (AL) during laparoscopic varicocelectomy (LV) in adolescents. MATERIALS AND METHODS: Data on 122 adolescents with unilateral varicocele who underwent laparoscopic varicocelectomy by a single urologist at our hospital were retrospectively studied. Age, varicocele grade, and testicular volume were collected, and postoperative data, including the operative time, recurrence, hydrocele, and catch-up growth, were assessed. Pre- and postoperative semen parameters in partial patients were compared between the groups. RESULTS: The preoperative data were comparable between the groups, and there were no significant intergroup differences in the postoperative recurrence rate, hydrocele rate, or the 12th- and 24th-month catch-up growth rates; however, the 12th-month catch-up growth rate was relatively low in the AL group compared with the AP group. The postoperative semen parameters in terms of concentration, motility, and morphology were (62.5 +/- 39.2) million/ml, (52.2 +/- 16.6)%, and (11.5 +/- 1.5)% in AP group, and (60.4 +/- 38.2) million/ml, (49.1 +/- 19.9)%, and (10.7 +/- 1.5)% in AL group, respectively. The semen parameters were improved in both groups (P < .05) when compared with preoperative data, and there was no statistically significant difference between the two procedures (P > .05). CONCLUSIONS: Considering the short-term impact on testicular restoration of the AL procedure, we suggest the AP procedure with fast and gentle dissection of the artery as the first choice. We also suggest a timely conversion to the AL procedure without hesitation when the first attempt fails. PMID- 26683753 TI - Can We Predict the Outcome of Varicocelectomy Based on the Duration of Venous Reflux? AB - OBJECTIVE: To investigate the outcome of varicocelectomy based on the duration of venous reflux (DVR) of the pampiniform plexus veins. MATERIALS AND METHODS: In total, 138 patients with clinically palpable varicoceles were evaluated for DVR with color Doppler ultrasonography from May 2009 to August 2014. The DVR was defined as the DVR of a varicocele in the supine position during the Valsalva maneuver. Patients with bilateral, recurrent, or subclinical varicoceles; hormonal imbalances involving follicle-stimulating hormone, luteinizing hormone, or total testosterone; azoospermia; and intraoperative or postoperative complications were excluded. Of the 138 patients, 76 met the inclusion criteria. All patients were treated with subinguinal microscopic varicocelectomy. Restoration of all three semen parameters (concentration, motility, and morphology) to normal values 6 months postoperatively was considered to indicate treatment success. The patients were divided into those with a DVR of <4.5 seconds (Group 1) and >=4.5 seconds (Group 2). RESULTS: The mean age of the patients was 29.39 (+/-6.03) years. No statistically significant relationship was found between the success rate and varicocele grade. The cutoff DVR value was calculated as 4.5 seconds using a receiver operating characteristics curve according to patients who underwent successful treatment. The success rates of Groups 1 and 2 were 40.0% and 88.2%, respectively (P = .0001). CONCLUSION: The results of this analysis indicate that a DVR of >=4.5 seconds predicts better outcomes of varicocelectomy. PMID- 26683754 TI - The Role of Prophylactic Antibiotics After Minimally Invasive Pyeloplasty With Ureteral Stent Placement in Children. AB - OBJECTIVE: To determine whether children discharged with prophylactic antibiotics following laparoscopic pyeloplasty with indwelling ureteral stent have a decrease risk of postoperative urinary tract infections (UTIs) compared to those discharged without antibiotics. MATERIALS AND METHODS: A retrospective review of all minimally invasive pyeloplasties performed at our institution from January 2009 to March 2015 was conducted. Patients were discharged home with or without daily prophylactic-dose antibiotics continued until 3 days after ureteral stent removal per surgeon preference. The primary outcome was incidence of culture positive UTI. Secondary outcomes included bacteriuria at time of stent removal and adverse events associated with extended antibiotic therapy. RESULTS: Of 163 pyeloplasties (106 robotic and 57 pure laparoscopic) performed over the study period, 126 patients were discharged on prophylactic antibiotics whereas 37 patients were discharged without prophylaxis. Groups were different with respect to median age (7.1 vs 12.0 years, P = .03) and median duration of ureteral stent (35 days vs 28 days, P = .02). The incidence of culture-positive UTI between the time of discharge and stent removal was comparably low between groups; 2/126 (1.6%) in the prophylaxis group and 1/37 (2.7%) in the group not on prophylaxis. At time of stent removal, perioperative urine culture was positive in 2/20 (10.0 %) patients who received prophylactic antibiotics and in 1/25 (4.0%) patients who did not (P = .54). CONCLUSION: The administration of extended prophylactic antibiotics showed no significant impact on the rate of UTI following minimally invasive pyeloplasty. PMID- 26683755 TI - Urodynamic Features and Significant Predictors of Bladder Outlet Obstruction in Patients With Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia and Small Prostate Volume. AB - OBJECTIVE: To investigate the clinical and urodynamic features of patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) according to their prostate size. MATERIALS AND METHODS: We analyzed 2039 LUTS/BPH patients who underwent urodynamic study between October 2004 and August 2013. We divided the patients into three groups according to their prostate size: small (<=30 mL), moderately enlarged (31-80 mL), and large prostate (>=81 mL) groups. We compared the groups regarding age, International Prostatic Symptom Score, maximal flow rate (Qmax), postvoided residual (PVR), serum prostate-specific antigen, prostate volume measured by ultrasonography, and urodynamic findings. RESULTS: Patients with a small prostate had better urodynamic outcomes than those with larger prostates in overall population. Although the total prostate volume significantly correlated with the bladder outlet obstruction (BOO) index (r = 0.51), BOO patients with a small prostate had similar Qmax, higher PVR, and lower voiding efficiency, compared to those with larger prostates. Moreover, urodynamic parameters indicating bladder abnormalities, including low compliance and involuntary detrusor contraction positivity, were similar among the groups in BOO patients. A higher proportion of detrusor underactivity was also observed in the small prostate group in BOO patients. Finally, when adjusting for potential confounding variables, we identified serum prostate-specific antigen levels (odds ratio, 1.34) and Qmax (odds ratio, 0.77) as significant predictors for BOO in LUTS/BPH patients with a small prostate. CONCLUSION: BOO patients with a small prostate showed higher PVR and poor voiding efficiency, as well as similar urodynamic bladder abnormalities, compared to those with moderately enlarged and large prostates. PMID- 26683757 TI - Re: Edwin E. Morales, Sonja Grill, Robert S. Svatek, et al. Finasteride Reduces Risk of Bladder Cancer in a Large Prospective Screening Study. Eur Urol 2016;69:407-10. PMID- 26683756 TI - Predictors of weight-loss response with glucagon-like peptide-1 receptor agonist treatment among adolescents with severe obesity. AB - In two previous, separate clinical trials, we demonstrated significant reductions in body mass index (BMI) with exenatide in adolescents with severe obesity. In the present study, we pooled data from these near identical trials to evaluate factors that may predict BMI reduction at 3 months. Data from 32 patients (mean age 14.3 +/- 2.2 years; 69% female; mean BMI 39.8 +/- 5.8 kg m(-2)) were included. Exenatide treatment consisted of 5 mcg twice daily for 1 month, followed by an increase to 10 mcg twice daily for 2 additional months. Predictor variables included baseline BMI, BMI percent change at 1 month, incidence of nausea or vomiting and baseline appetite and satiety measures. Treatment effects of percent change in BMI from baseline were estimated within predictor subgroups using generalized estimating equations with exchangeable working correlation and robust variance estimation for confidence intervals and P-values to account for paired observations. The pooled data treatment effect on absolute BMI at 3 months was -3.42% (95% confidence interval: -5.41%, -1.42%) compared to placebo. Within treated participants, appetite at baseline (treatment effect in high [-4.28%] vs. low [1.02%], P = 0.028) and sex (treatment effect in female [-4.78%] vs. male [0.76%], P = 0.007) were significant predictors of change in BMI at 3 months. Baseline BMI, BMI percent change at 1 month, age, incidence of nausea, vomiting, or other gastrointestinal symptoms and satiety scores did not predict 3-month responses. Sex and measures of appetite may serve as useful predictors of glucagon-like peptide-1 receptor agonist treatment response among adolescents with severe obesity. PMID- 26683758 TI - Re: Grace L. Lu-Yao, Peter C. Albertsen, Dirk F. Moore, Yong Lin, Robert S. DiPaola, Siu-Long Yao. Fifteen-year Outcomes Following Conservative Management Among Men aged 65 Years or Older with Localized Prostate Cancer. Eur Urol 2015;68:805-11. PMID- 26683759 TI - It Is Time to Harmonize the Design and Conduct of Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer. PMID- 26683760 TI - Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood eczema: The Generation R Study. AB - BACKGROUND: Exposure to low levels of vitamin D in fetal life might affect the developing immune system, and subsequently the risk of childhood eczema. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with the risk of eczema until the age of 4 years. METHODS: In a population-based prospective cohort study of 3019 mothers and their children, maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels (severely deficient <25.0 nmol/l, deficient 25.0-49.9 nmol/l, sufficient 50.0-74.9 nmol/l, optimal >=75.0 nmol/l). Eczema was prospectively assessed by annual questionnaires until the age of 4 years. Eczema patterns included never, early (age <=1 year only), late (age >1 year only), and persistent eczema (age <= and >1 year). Data were assessed using the generalized estimating equations and multinomial regression models. RESULTS: Compared with the optimal 25-hydroxyvitamin D group, sufficient, deficient, and severely deficient groups of 25-hydroxyvitamin D level in mid gestation were not associated with the risk of overall eczema (odds ratios [95% confidence interval]: 1.09 [0.82, 1.43], 1.04 [0.87, 1.25], and 0.94 [0.81, 1.10], p-values for trend >0.05), nor with eczema per year or eczema patterns in children up to the age of 4 years. Similarly, we observed no associations of 25 hydroxyvitamin D groups at birth with any eczema outcome. CONCLUSION: Our results suggest that levels of 25-hydroxyvitamin D in mid-gestation and at birth are not associated with the risk of overall eczema, eczema per year, or eczema patterns among children until the age of 4 years. PMID- 26683761 TI - Parallelism in adaptive radiations of experimental Escherichia coli populations. AB - Adaptive radiations are major contributors to species diversity. Although the underlying mechanisms of adaptive radiations, specialization and trade-offs, are relatively well understood, the tempo and repeatability of adaptive radiations remain elusive. Ecological specialization can occur through the expansion into novel niches or through partitioning of an existing niche. To test how the mode of resource specialization affects the tempo and repeatability of adaptive radiations, we selected replicate bacterial populations in environments that promoted the evolution of diversity either through niche expansion or through niche partitioning, and in a third low-quality single-resource environment, in which diversity was not expected to evolve. Colony size diversity evolved equally fast in environments that provided ecological opportunities regardless of the mode of resource specialization. In the low-quality environments, diversity did not consistently evolve. We observed the largest fitness improvement in the low quality environment and the smallest the glucose-limited environment. We did not observe a change in the rate of evolutionary change in either trait or environment, suggesting that the pool of beneficial mutations was not exhausted. Overall, the mode of resource specialization did not affect the tempo or repeatability of adaptive radiations. These results demonstrate the limitations of eco-evolutionary feedbacks to affect evolutionary outcomes. PMID- 26683762 TI - Drug-related covariates should be considered in Bayesian network meta-analysis of pharmacological interventions. PMID- 26683764 TI - Electrochemistry of Carbon Dioxide on Carbon Electrodes. AB - Carbon electrodes have the advantages of being chemically inert at negative potential ranges in all media and high offset potentials for hydrogen evolution in comparison to metal electrodes, and therefore are the most suitable electrodes for electrochemistry and electrochemical conversion of CO2 into valuable chemicals. Herein we summarize on carbon electrodes the voltammetry, electrochemical and electrocatalytic CO2 reduction, as well as electron synthesis using CO2 and carbon electrodes. The electrocatalytic CO2 reduction using carbocatalyts and the future activities about electrochemical CO2 conversion are highlighted. PMID- 26683763 TI - Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis. AB - BACKGROUND & AIMS: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV). METHODS: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes. RESULTS: In the Japanese phase 3 study, SVR12 was achieved by 91% of patients with cirrhosis (n = 22) and 84% of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84% of patients with cirrhosis (n = 206) and by 85% of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5-4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation. CONCLUSIONS: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834. PMID- 26683765 TI - Effects of two different organic amendments addition to soil on sorption desorption, leaching, bioavailability of penconazole and the growth of wheat (Triticum aestivum L.). AB - This study investigated the effects of sugarcane bagasse compost (SBC) and chicken manure compost (CMC) on the sorption-desorption, leaching and bioavailability of the fungicide penconazole in soil in a laboratory setting. The autoclave-treated SBC or CMC was applied at 2.5% and 5.0% (w/w). Results of batch equilibrium experiments exhibited that the sorption capacity of soils for penconazole was significantly promoted by the addition of SBC or CMC, whereas desorption of penconazole was drastically reduced; the influence was enhanced as the amount of organic amendments increased. Results of column leaching experiment indicated that the addition of SBC or CMC significantly limited the vertical movement of penconazole through the soil columns, considerably decreasing the content of penconazole in the soil leachate. Furthermore, results of bioavailability experiments demonstrated that the addition of organic amendments (SBC or CMC) remarkably influenced the uptake and translocation of penconazole, decreased penconazole accumulation in the plant tissues and increased the plant elongation and biomass. These data revealed important changes in pesticide behavior under SBC or CMC application, which should be useful for developing strategies to protect groundwater and crops from contamination from the residual pesticides in soil. PMID- 26683766 TI - An innovative method for water resources carrying capacity research--Metabolic theory of regional water resources. AB - The shortage and uneven spatial and temporal distribution of water resources has seriously restricted the sustainable development of regional society and economy. In this study, a metabolic theory for regional water resources was proposed by introducing the biological metabolism concept into the carrying capacity of regional water resources. In the organic metabolic process of water resources, the socio-economic system consumes water resources, while products, services and pollutants, etc. are output. Furthermore, an evaluation index system which takes into the characteristics of the regional water resources, the socio-economic system and the sustainable development principle was established based on the proposed theory. The theory was then applied to a case study to prove its availability. Further, suggestions aiming at improving the regional water carrying capacity were given on the basis of a comprehensive analysis of the current water resources situation. PMID- 26683767 TI - Reality Television Programs Are Associated With Illegal Drug Use and Prescription Drug Misuse Among College Students. AB - BACKGROUND: Reality television watching and social media use are popular activities. Reality television can include mention of illegal drug use and prescription drug misuse. OBJECTIVES: To determine if reality television and social media use of Twitter are associated with either illegal drug use or prescription drug misuse. METHODS: Survey of 576 college students in 2011. Independent variables included watching reality television (social cognitive theory), parasocial interaction (parasocial interaction theory), television hours watched (cultivation theory), following a reality television character on Twitter, and demographics. Outcome variables were illegal drug use and prescription drug misuse. RESULTS: Watching reality television and also identifying with reality TV program characters were each associated with greater odds for illegal drug use. Also, following a reality TV character on Twitter had greater odds for illegal drug use and also in one analytical model for prescription drug misuse. No support was seen for cultivation theory. Those born in the United States had greater odds for illegal drug use and prescription drug misuse. Women and Asians had lower odds for illegal drug use. African Americans and Asians had lower odds for prescription drug misuse. CONCLUSIONS/IMPORTANCE: Physicians, psychologists, and other healthcare practitioners may find it useful to include questions in their clinical interview about reality television watching and Twitter use. Physician and psychology groups, public health practitioners, and government health agencies should consider discussing with television broadcasting companies the potential negative impact of including content with illegal drugs and prescription drug misuse on reality television programs. PMID- 26683768 TI - MicroRNA-555 has potent antiviral properties against poliovirus. AB - Vaccination with live-attenuated polio vaccine has been the primary reason for the drastic reduction of poliomyelitis worldwide. However, reversion of this attenuated poliovirus vaccine occasionally results in the emergence of vaccine derived polioviruses that may cause poliomyelitis. Thus, the development of anti poliovirus agents remains a priority for control and eradication of the disease. MicroRNAs (miRNAs) have been shown to regulate viral infection through targeting the viral genome or reducing host factors required for virus replication. However, the roles of miRNAs in poliovirus (PV) replication have not been fully elucidated. In this study, a library of 1200 miRNA mimics was used to identify miRNAs that govern PV replication. High-throughput screening revealed 29 miRNAs with antiviral properties against Sabin-2, which is one of the oral polio vaccine strains. In particular, miR-555 was found to have the most potent antiviral activity against three different oral polio attenuated vaccine strains tested. The results show that miR-555 reduced the level of heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNP C) required for PV replication in the infected cells, which in turn resulted in reduction of PV positive-strand RNA synthesis and production of infectious progeny. These findings provide the first evidence for the role of miR-555 in PV replication and reveal that miR-555 could contribute to the development of antiviral therapeutic strategies against PV. PMID- 26683769 TI - Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM. AB - Mutant Kras and chronic pancreatitis are the most common pathological events involved in human pancreatic cancer. It has been demonstrated that c-Raf is responsible for transmitting signals from mutant Ras to its downstream signals including MEK-ERK and for initiating carcinogenesis. The soluble epoxide hydrolase (sEH), a pro-inflammatory enzyme, generally inactivates anti inflammatory and anti-pain epoxyeicosatrienoic acids (EETs). Herein, we have synthesized a novel compound of trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl) ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM) via modifying the central phenyl ring of sorafenib and confirmed its dual inhibition of sEH and c-Raf by recombinant kinase activity assay. Pharmacokinetic analysis revealed that oral dosing of t-CUPM resulted in higher blood levels than that of sorafenib throughout the complete time course (48 h). The effect of t-CUPM on the inhibition of mutant Kras(G12D)-initiated murine pancreatic cancer cell growth was determined using the mouse pancreatic carcinoma cell model obtained from LSL Kras(G12D)/Pdx1-Cre mice and showed that t-CUPM significantly inhibited this murine pancreatic carcinoma cell growth both in vitro and in mice in vivo. Inhibition of mutant Kras-transmitted phosphorylations of cRAF/MEK/ERK was demonstrated in these pancreatic cancer cells using Western blot assay and immunohistochemical approach. Modulation of oxylipin profile, particularly increased EETs/DHET ratio by sEH inhibition, was observed in mice treated with t CUPM. These results indicate that t-CUPM is a highly potential agent to treat pancreatic cancer via simultaneously targeting c-Raf and sEH. PMID- 26683770 TI - Deoxypodophyllotoxin triggers parthanatos in glioma cells via induction of excessive ROS. AB - Parthanatos is a new form of programmed cell death that is regulated by hyper activated PARP-1, and is emerging as a new strategy to kill cancer cells. Deoxypodophyllotoxin (DPT) is a natural chemical that is found to induce cancer cell death, in which the role of parthanatos is unknown. Thus, we investigated this issue in this study by using glioma cell lines and mice model of xenograft glioma. We found that DPT induced glioma cell death in vitro and inhibited the growth of xenograft glioma in vivo, which was accompanied with parthanatos related biochemical events including expressional upregulation of PARP-1, cytoplasmic accumulation of PAR polymer, and nuclear translocation of AIF. In vitro study revealed that genetic knockdown of PARP-1 with small interfering RNA attenuated DPT-induced elevation in the cytoplasmic PAR-polymer and the nuclear AIF, as well as protected glioma cells against the toxicity of DPT. Further, antioxidant NAC, as well as PARP-1 inhibitor 3AB, not only alleviated the overproduction of ROS caused by DPT, but also reversed the above-mentioned biochemical events, maintained mitochondrial membrane potential and rescued glioma cells death. Therefore, we demonstrated that deoxypodophyllotoxin triggered parthanatos in glioma cells via induction of excessive ROS. PMID- 26683773 TI - A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells. AB - Glioblastoma multiforme (GBM), a highly malignant brain tumor, accounts for half of all gliomas. Despite surgery, radiation and chemotherapy, the median survival is between 12 and 15 months. The poor prognosis is due to tumor recurrence attributed to chemoresistant glioma cancer stem cells (GSCs). Here we examined the effects of a novel compound NEO212, which is composed of two covalently conjugated anti-cancer compounds - temozolomide (TMZ) and perillyl alcohol (POH), on GSCs expressing either the proneural or mesenchymal gene signatures. These GSCs were obtained from patient-derived tumor tissue. Our findings demonstrate that NEO212 is 10 fold more cytotoxic to GSCs than TMZ (standard-of-care). Furthermore, NEO212 is effective against both proneural and clinically aggressive mesenchymal GSC subtypes. The mechanism of NEO212 mediated-cytotoxicity is through double-strand DNA breaks and apoptosis. In vivo studies show that NEO212 significantly delays tumor growth of both proneural and mesenchymal tumor stem cell populations. Patient-derived GSCs and tumors derived from these cells are highly reflective of the heterogeneity in human GBM. The efficacy of NEO212 against both GSC subtypes indicates that NEO212 has great clinical potential to effectively target GBM. PMID- 26683772 TI - Bromodomain and hedgehog pathway targets in small cell lung cancer. AB - Small cell lung cancer (SCLC) is an extremely aggressive cancer that frequently recurs. Twenty-three human SCLC lines were selected representing varied Myc status. Gene expression of lung cancer, stem-like, hedgehog pathway, and notch pathway genes were determined by RT(2)-PCR array and Exon 1.0 ST array. Etoposide and topotecan concentration response was examined. The IC50's for etoposide and topotecan ranged over nearly 3 logs upon 96 hrs exposure to the drugs. Myc status, TOP2A, TOP2B and TOP1 mRNA expression or topoisomerase 1 and topoisomerase 2 protein did not account for the range in the sensitivity to the drugs. gamma-secretase inhibitors, RO429097 and PF-03084014, had little activity in the SCLC lines over ranges covering the clinical Cmax concentrations. MYC amplified lines tended to be more sensitive to the bromodomain inhibitor JQ1. The Smo antagonists, erismodegib and vismodegib and the Gli antagonists, HPI1 and SEN 450 had a trend toward greater sensitivity of the MYC amplified line. Recurrent SCLC is among the most recalcitrant cancers and drug development efforts in this cancer are a high priority. PMID- 26683771 TI - MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. AB - The molecular mechanisms underlying the aggressive behavior of MYCN driven neuroblastoma (NBL) is under intense investigation; however, little is known about the impact of this family of transcription factors on the splicing program. Here we used high-throughput RNA sequencing to systematically study the expression of RNA isoforms in stage 4 MYCN-amplified NBL, an aggressive subtype of metastatic NBL. We show that MYCN-amplified NBL tumors display a distinct gene splicing pattern affecting multiple cancer hallmark functions. Six splicing factors displayed unique differential expression patterns in MYCN-amplified tumors and cell lines, and the binding motifs for some of these splicing factors are significantly enriched in differentially-spliced genes. Direct binding of MYCN to promoter regions of the splicing factors PTBP1 and HNRNPA1 detected by ChIP-seq demonstrates that MYCN controls the splicing pattern by direct regulation of the expression of these key splicing factors. Furthermore, high expression of PTBP1 and HNRNPA1 was significantly associated with poor overall survival of stage4 NBL patients (p <= 0.05). Knocking down PTBP1, HNRNPA1 and their downstream target PKM2, an isoform of pro-tumor-growth, result in repressed growth of NBL cells. Therefore, our study reveals a novel role of MYCN in controlling global splicing program through regulation of splicing factors in addition to its well-known role in the transcription program. These findings suggest a therapeutically potential to target the key splicing factors or gene isoforms in high-risk NBL with MYCN-amplification. PMID- 26683774 TI - The synthetic beta-nitrostyrene derivative CYT-Rx20 induces breast cancer cell death and autophagy via ROS-mediated MEK/ERK pathway. AB - The beta-nitrostyrene family has been shown to suppress cancer cell proliferation and induce programmed cell death. However, mechanisms underlying beta nitrostyrenes remain less evaluated. Here, we synthesized a beta-nitrostyrene derivative, CYT-Rx20, and characterized its anticancer effect and involving mechanisms in breast cancer. We found that CYT-Rx20 arrested breast cancer cells at G2/M phase and decreased cell viability by activating the caspase cascade, accompanying with increases of poly (ADP-ribose) polymerase (PARP) cleavage and gamma-H2AX expression. On the other hand, up-regulation of Beclin-1, ATG5, and LC 3 was observed in CYT-Rx20-induced autophagy, which was evidently shown by transmission electron microscopy. In addition to these, CYT-Rx20-induced breast cancer cell death, intracellular reactive oxygen species (ROS) formation and expression of phospho-ERK1/2, Beclin-1, and LC-3 were significantly reversed in the presence of N-acetyl-l-cysteine (NAC), a thiol antioxidant. Furthermore, the cytotoxicity of CYT-Rx20 was enhanced by co-treatment with the autophagy inhibitor chloroquine or bafilomycin A1, suggesting that an incomplete autophagy process could deteriorate CYT-Rx20-induced cytotoxicity. In nude mice xenograft study, CYT-Rx20 significantly reduced orthotopic tumor growth. Immunohistochemical analysis revealed elevated expression of phospho-ERK1/2 and LC-3 in tumor tissues of the mice treated with CYT-Rx20. Together, we propose that CYT-Rx20 may have potential to be further developed into a beta-nitrostyrene based anticancer compound for the treatment of breast cancer. PMID- 26683775 TI - Molecular mechanisms of microRNAs in regulating epithelial-mesenchymal transitions in human cancers. AB - The epithelial-mesenchymal transition (EMT) provides a strong driving force in the progression of various human cancers and the development of chemoresistance. Recently, numbers of studies have demonstrated that microRNAs (miRNAs), by post transcriptionally silencing EMT-related molecules, can promote or inhibit the EMT process and play pivotal roles in effectively manipulating the occurrence, development, invasion, and metastasis of cancers. MiRNAs can also control the EMT or be controlled by genetic modification and mutual regulation, especially negative feedback. Therefore, miRNAs can be viewed as either oncogenes or tumor suppressor genes to facilitate or retard the EMT, resulting in far-reaching impact on tumor metastasis and effective diagnosis, treatment, and prognosis. PMID- 26683776 TI - The circadian clock gene Bmal1 acts as a potential anti-oncogene in pancreatic cancer by activating the p53 tumor suppressor pathway. AB - Disruption of the circadian clock has been shown to be associated with tumor development. This study aimed to investigate the role of the core circadian gene Bmal1 in pancreatic cancer (PC). We first found that the levels of Bmal1 were downregulated in PC samples and were closely correlated with the clinicopathological features of patients. To dissect the underlying mechanism, we performed a RNA-seq assay followed by systematic gene function and pathway enrichment analyses. We detected an anti-apoptotic and pro-proliferative transcriptome profile after Bmal1 knockdown in PC cells. Further in vitro and in vivo studies confirmed that Bmal1 overexpression significantly inhibited cell proliferation and invasion and induced G2/M cell cycle arrest, whereas Bmal1 knockdown promoted PC growth, as demonstrated in Bmal1-manipulated AsPC-1 and BxPC-3 cell lines. Our mechanistic studies indicated that Bmal1 could directly bind to the p53 gene promoter and thereby transcriptionally activate the downstream tumor suppressor pathway in a p53-dependent manner. In sum, our findings suggest that Bmal1 acts as an anti-oncogene in PC and represents a potential biomarker for its diagnosis. PMID- 26683777 TI - The role of occupational therapists in the contexts of a natural disaster: a scoping review. AB - PURPOSE: To identify and inform the experience and roles of occupational therapists (OTs) in the contexts of a natural disaster. METHOD: This scoping review was conducted via five steps: (1) identify the research question, (2) identify relevant academic articles published between 2000 and 2014 in English, (3) select articles based on the inclusion criteria, (4) chart the data and (5) collate, summarise, and report the results of the selected articles. The results were presented using descriptive numerical and thematic analyses. RESULTS: OTs can prepare a plan for evacuation of people with disabilities and their accommodation before a disaster occurs. Immediately after a disaster, they can provide emergency services for injuries and provide education and training in coping skills for psychological distress via a community-based rehabilitation approach. Consistent services for survivors' mental health and for building the OTs' capacity as part of disaster management are focussed on in the recovery phase. CONCLUSION: The potential roles of OTs across the spectrum of a natural disaster were identified via this scoping review. This review will help OTs to become involved in a disaster management system for vulnerable groups across the three phases of preparedness to, respond to and recovery from a disaster. Implication for Rehabilitation Occupational therapists can be involved in disaster management to prepare for, respond to and recover from a natural disaster. Consistent services for psychological distress are needed for people affected by a disaster to return to normalcy. Community-based rehabilitation (CBR) is an important approach to help a wider group of people respond to a natural disaster in a timely manner. PMID- 26683778 TI - The Best Use of the Charlson Comorbidity Index With Electronic Health Care Database to Predict Mortality. AB - BACKGROUND: The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index. METHODS: Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion. RESULTS: We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0-71.64% for Charlson index of >=5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4 level score. CONCLUSIONS: Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities. PMID- 26683779 TI - Clocks Moving at Different Speeds: Cultural Variation in the Satisfaction With Wait Time for Outpatient Care. AB - OBJECTIVE: To explore racial/ethnic differences in satisfaction with wait time of scheduled office visits by comparing electronic health record (EHR)-based, patient-reported, and patient satisfaction with wait time STUDY SETTING: : A large multispecialty ambulatory care organization in Northern California. Patient experience surveys were collected between 2010 and 2014. Surveys were mailed after randomly selected nonurgent visits. Returned survey data were linked to EHR data for surveyed visits. STUDY DESIGN: Observational, retrospective study designed to assess differences in patient-reported wait time, wait-time satisfaction, and actual EHR-recorded wait time with respect to self-reported race/ethnicity. Multivariate regression models with provider random effects were used to evaluate differences. RESULTS: Asian subgroups (Chinese, Asian Indian, Filipino, Japanese, Korean, and Vietnamese) and Latinos gave poorer ratings for wait time than non-Hispanic whites (NHWs). The average wait time reported by Asians was longer than that reported by NHWs. On the basis of EHR data, however, no minority group was likely to wait longer, and all, except for Japanese (10%), were more likely to be late for the appointment (16%: Filipino and 23%: Asian Indian), than NHWs (13%). CONCLUSIONS: Given actual wait times, Asians perceive longer wait time and were less satisfied with wait times. Asians may have different expectations about wait time at the clinic. PMID- 26683780 TI - Performance of the Medicare Consumer Assessment of Health Care Providers and Systems (CAHPS) Physical Functioning Items. AB - BACKGROUND: Physical functioning is an important health domain for adults. OBJECTIVE: Evaluate physical functioning items in Medicare beneficiaries. RESEARCH DESIGN: Survey data from the 2010 Consumer Assessment of Healthcare Providers and Systems Medicare survey. SUBJECTS: The 366,701 respondents were 58% female; 38% were 75 or older; 57% had high school education or less. MEASURES: Walking, getting in or out of chairs, bathing, dressing, toileting, and eating assessed with 3 response choices: unable to do, have difficulty, do not have difficulty. RESULTS: Pearson correlations among the 6 items ranged from 0.515 to 0.835 (coefficient alpha=0.92). A single factor categorical factor analytic model fit the data well (comparative fit index=0.998; root mean square error of approximation=0.083). The item with the highest percentage of respondents reporting no difficulty was eating, followed by toileting, dressing, bathing, getting in and out of a chair, and walking. Threshold parameters from an item response theory-graded response model ranged from -1.983 (between unable to do and have difficulty eating) to -0.551 (between have difficulty and no difficulty walking). Item discrimination parameters ranged from 4.632 (walking) to 8.228 (dressing). IRT-scored physical functioning scores correlated with self-rated general health (r=0.389, n=344,843, P<0.0001) mental health (r=0.296, n=351,254, P<0.0001) and number of chronic conditions (r=-0.229, n=284,507, P<0.0001). CONCLUSIONS: The physical functioning items target relatively easy activities, providing information for a minority of people in the sample with the lowest levels of physical functioning. Items representing higher levels of physical functioning are needed for the majority of the Medicare beneficiaries. PMID- 26683781 TI - Development of a Novel Composite Process Measure for Venous Thromboembolism Prophylaxis. AB - BACKGROUND: Postoperative venous thromboembolism (VTE) is important clinically, and VTE quality metrics are used in public reporting and pay-for-performance programs. However, current VTE outcome measures are not valid due to surveillance bias, and the Surgical Care Improvement Project (SCIP-VTE-2) process measure only requires prophylaxis within 24 hours of surgery. OBJECTIVES: We sought to (1) develop a novel measure of VTE prophylaxis that requires early ambulation, mechanical prophylaxis, and chemoprophylaxis throughout the hospitalization, and (2) compare hospital performance on the SCIP-VTE-2 process measure to this novel measure. RESEARCH DESIGN: A new composite measure of ambulation, sequential compression device (SCD), and chemoprophylaxis component measures was developed. The ambulation component required daily ambulation, the SCD component required documentation of continuous use, and the chemoprophylaxis component required patient-appropriate and medication-appropriate dosing and administration. Requirements could also be met with component-specific exceptions. Surgical patients at an academic center from 2012 to 2013 were assessed for SCIP-VTE-2 and composite measure adherence. RESULTS: Of 786 patients, 589 (74.9%) passed the ambulation measure, 494 (62.8%) passed the SCD measure, and 678 (86.3%) passed the chemoprophylaxis measure. A total of 268 (91.8%) SCD failures and 46 (42.6%) chemoprophylaxis failures were ordered but not administered. When comparing the 2 measures, 784 (99.7%) passed SCIP-VTE-2, whereas only 364 (46.3%) passed the composite measure (P<0.001). CONCLUSIONS: This new measure incorporates the critical aspects of VTE prevention to ensure defect-free care. After additional evaluation, this composite VTE prophylaxis measure with appropriate exclusion criteria may be a better alternative to existing VTE process and outcome measures. PMID- 26683782 TI - The Impact of Hospital Size on CMS Hospital Profiling. AB - BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) profile hospitals using a set of 30-day risk-standardized mortality and readmission rates as a basis for public reporting. These measures are affected by hospital patient volume, raising concerns about uniformity of standards applied to providers with different volumes. OBJECTIVES: To quantitatively determine whether CMS uniformly profile hospitals that have equal performance levels but different volumes. RESEARCH DESIGN: Retrospective analysis of patient-level and hospital-level data using hierarchical logistic regression models with hospital random effects. Simulation of samples including a subset of hospitals with different volumes but equal poor performance (hospital effects=+3 SD in random-effect logistic model). SUBJECTS: A total of 1,085,568 Medicare fee-for-service patients undergoing 1,494,993 heart failure admissions in 4930 hospitals between July 1, 2005 and June 30, 2008. MEASURES: CMS methodology was used to determine the rank and proportion (by volume) of hospitals reported to perform "Worse than US National Rate." RESULTS: Percent of hospitals performing "Worse than US National Rate" was ~40 times higher in the largest (fifth quintile by volume) compared with the smallest hospitals (first quintile). A similar gradient was seen in a cohort of 100 hospitals with simulated equal poor performance (0%, 0%, 5%, 20%, and 85% in quintiles 1 to 5) effectively leaving 78% of poor performers undetected. CONCLUSIONS: Our results illustrate the disparity of impact that the current CMS method of hospital profiling has on hospitals with higher volumes, translating into lower thresholds for detection and reporting of poor performance. PMID- 26683784 TI - Multiple-domain Versus Single-domain Measurements of Socioeconomic Status (SES) for Predicting Nonadherence to Statin Medications: An Observational Population based Cohort Study. AB - INTRODUCTION: Low socioeconomic status (SES) should be a robust predictor of medication nonadherence because it shares key features with the theoretical origins of this phenomenon. However, population-based studies have demonstrated weak associations overall, possibly because SES is inadequately represented. We compared the performance of multiple versus single-domain measures of SES as predictors of statin adherence. METHODS: This retrospective cohort study used population-based administrative data mapped to area-level census information of individuals who received a statin medication following a hospitalization for coronary heart disease. One-year adherence was calculated by dividing the sum of all tablets dispensed by the total number of days in the observation period (365 d following the first statin dispensation). Logistic regression models were constructed and the relative impact of each SES measure was assessed by its adjusted odds ratio (OR) and improvement over the predictive accuracy of a reference model that included non-SES factors only. RESULTS: More than two thirds (ie, 68.8%; 6517/9478) of eligible individuals exhibited optimal adherence (ie, >=80%). The estimated impact of SES on optimal adherence differed depending on the SES measure tested. The highest performing single-domain measure, household income (OR=0.75; 95% confidence interval, 0.63-0.90; model c-statistic improvement 0.5%, P=0.04) generated a similar result to the multiple-domain measure (adjusted OR=0.74; 95% confidence interval, 0.62-0.88; model c-statistic improvement 0.7%, P=0.01). CONCLUSION: Multidomain measurements of SES using administrative databases mapped to census data are not associated with better performance in predicting statin medication adherence compared with single-domain measures such as household income. PMID- 26683786 TI - Effects of Endurance Exercise Training on The Motor and Non-Motor Features of Parkinson's Disease: A Review. PMID- 26683785 TI - Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson's Disease: Considerations from a Pilot Study. AB - BACKGROUND: Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in "healthy" adults. Although individuals with neurodegenerative disorders such as Parkinson's disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE: To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS: A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD "healthy" controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), 3 weeks, 3 months, and 1 year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non surgery peers. RESULTS: Over two years we screened 152 older adult surgery or non surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non surgery PD individuals. CONCLUSION: This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID- 26683788 TI - Extra-anatomic Course of a Right Ventricular Pacing Lead: Clinical Implications. PMID- 26683789 TI - Emergency Department Re-Presentation for Atrial Fibrillation and Atrial Flutter. AB - BACKGROUND: Identification and appropriate management of patients with atrial fibrillation (AF) is critical to mitigate the consequences of the disease. We sought to assess the frequency and pattern of the emergency department (ED) use by patients who presented with AF and/or atrial flutter (AFL) in a midsized Canadian hospital. METHODS: We conducted a retrospective cohort analysis of patients who presented to the ED with AF and/or AFL during the calendar years 2010-2012. Patients were identified using the MUSE (General Electric Healthcare, Bucks, United Kingdom) electrocardiogram database and matched with the National Ambulatory Care Reporting System and Discharge Abstract Database up to and including December 31, 2013, a follow-up period of 12 months. The number of presentations and time between visits was assessed. Admissions were identified and lengths of stay and reason for admission were recorded. RESULTS: We identified 1361 patients who represented a total of 4783 visits to the ED, a mean of 2.8 +/- 2.9 visits per patient with 949 (69.7%) who returned for a subsequent ED visit in the subsequent 12 months. Mean time between base and subsequent visits was 136.8 +/- 114.2 days. ED visits generated 1462 admissions (63.0% at repeat ED visits); mean length of stay was 9.7 +/- 16.0 days. Stroke or transient ischemic attack accounted for 80 return visits and 8 deaths in 77 patients, 74% of whom with subtherapeutic or no anticoagulation medication. CONCLUSIONS: Presentation to the ED with AF and/or AFL, either as a primary reason for consultation or as a secondary diagnosis, was associated with a high risk of subsequent re-presentation and hospital admission. PMID- 26683790 TI - Prazosin for Veterans with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence: A Clinical Trial. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is an important and timely clinical issue particularly for combat veterans. Few pharmacologic options are available to treat PTSD, particularly among military personnel, and they are not based on rational neurobiology. The evidence for noradrenergic dysregulation in PTSD is strong, and the alpha-adrenergic agonist prazosin is one of the most promising medications to treat sleep disturbances associated with PTSD as well as PTSD symptoms among both veterans and civilians. Evidence also implicates noradrenergic dysregulation in the pathophysiology of alcohol dependence (AD); prazosin also may have efficacy in treating this disorder. The use of prazosin represents a rational and compelling approach for the treatment of PTSD and comorbid AD. Given the high rates of comorbid AD in trauma survivors with PTSD, and the enormous impact that these comorbid disorders have on psychosocial function and well-being, finding effective treatments for this population is of high clinical importance. METHODS: Ninety-six veterans with PTSD and comorbid AD were randomized to receive prazosin (16 mg) or placebo in an outpatient, randomized, double-blind, clinical trial for 13 weeks. Main outcomes included symptoms of PTSD, sleep disturbances, and alcohol use. RESULTS: Symptoms of PTSD improved over time, but contrary to the hypothesis, there was no medication effect on PTSD symptoms, or on sleep. Alcohol consumption also decreased over time, but there were no significant differences in outcomes between medication groups. CONCLUSIONS: Prazosin was not effective in treating PTSD symptoms, improving sleep, or reducing alcohol consumption overall in this dually diagnosed group. This does not support the use of prazosin in an actively drinking population and suggests that the presence of a comorbid condition affects the efficacy of this medication. This study highlights the importance of conducting clinical trials in "real-world" patients, as results may vary based on comorbid conditions. PMID- 26683791 TI - Basal and stimulated calcitonin levels in patients with type 2 diabetes did not change during 1 year of Liraglutide treatment. AB - BACKGROUND AND AIMS: The administration of Liraglutide, a long-acting GLP-1 receptor (GLP-1R) agonist, is associated with C-cell adenomas and carcinomas in rats. In humans, GLP-1R is highly expressed in C-cells hyperplasia (CCH) and in medullary thyroid cancer (MTC), though no changes in basal serum calcitonin (bCT) levels were recorded in type 2 diabetic (T2DM) patients treated with Liraglutide. To diagnose the possible development of CCH during Liraglutide treatment, we evaluated CT levels stimulated by calcium test (sCT). MATERIALS AND METHODS: bCT and sCT and metabolic and anthropometric parameters were evaluated in 26 T2DM patients at baseline and at 1, 3, 6 and 12 months of treatment. RESULTS: In all patients, bCT remained within the normal range during the entire study period. In females and males, the higher sCT values were reached after 3 months and 1 month, respectively, with a progressive reduction at 6-12 months. The greater decrease of HbA1c values was reached at 3 months, while body weight and waist circumference decreased over the first 4 weeks of therapy. Lipase levels significantly increased, with a peak value at 1 month. CONCLUSION: The chronic administration of Liraglutide did not lead to statistically significant variations in both bCT and sCT. Stimulated CT levels increased, though always below the normal range, during the first 1-3 months of treatment, and progressively decreased to baseline levels. This finding is consistent with the effects recorded at the glycometabolic level, and suggests the possible induction of a drug tolerance involving also the C cells and thus preventing CCH. PMID- 26683792 TI - Reduced expression of ERp46 under diabetic conditions in beta-cells and the effect of liraglutide. AB - BACKGROUND: Diabetes mellitus is characterized by peripheral insulin resistance, hyperglycemia and defective insulin secretion. Insulin producing pancreatic beta cells are equipped with a highly developed endoplasmic reticulum (ER) and thus are affected by ER stress under hyperglycemic conditions. We have previously studied the influence of high glucose on cultured beta-cells in vitro. Proteomic analysis revealed a number of proteins involved in glucose toxicity, while further biochemical analysis identified the endoplasmic reticulum protein ERp46 as a molecule with a possible role in insulin production at the post translational level. In addition, the involvement of incretin hormone glucagon like peptide 1 (GLP-1) in diabetes proposes that incretin-mimetic compounds may be among the optimal choices in future therapeutic interventions; therefore their effects on various aspects of the pathogenesis of diabetes mellitus should be explored in detail. Based on the above, we examined the possible involvement of ERp46 in insulin production and the effect of the GLP-1 analogue liraglutide on the expression of ERp46 in vitro, in beta-cells cultured under high glucose conditions and in vivo, in the mouse db/db diabetic model, where pronounced hyperglycemia is a key characteristic. RESULTS: Confocal microscopy revealed areas of co-localization of ERp46 and pro-insulin in pancreatic islets. In order to explore the possible interaction between ERp46 and insulin immunoprecipitation was used. In extracts from cultured beta-cells, antibodies against pro-insulin co precipitated ERp46 and antibodies against ERp46 co-precipitated pro-insulin, as shown by Western blotting. Furthermore, data from a proximity ligation assay positioned these two molecules closer than 30nm in distance. When pancreatic beta cells were cultured in high glucose conditions they exhibited a decrease in ERp46 expression, while treatment with the GLP-1 analogue liraglutide restored ERp46 levels, leading to a significant increase of ERp46 in comparison to hyperglycemic conditions. In the diabetic mouse model db(-)/db, ERp46 expression was reduced in pancreatic islets, as documented by morphological and biochemical techniques. This decrease was abolished after treatment with the GLP-1 analogue in a dose dependent manner. In an attempt to understand the underlying mechanism, we examined the sequence of the promoter of ERp46 and found consensus motifs that can be recognized by transcription factors ATF6 and XBP1. Subsequently, we performed chromatin immunoprecipitation assay and demonstrated that treatment of beta-TC-6 cells with 25mmol/L glucose decreases gradually the binding enrichment of ATF6 and XBP1 in ERp46 gene promoter. CONCLUSIONS: We propose that since ERp46 is a member of the disulfide isomerases family, it is likely to play a key role in insulin biosynthesis and its reduction under high glucose conditions may be a novel contributor to the glucotoxicity of beta-cells. In addition, the GLP-1 analogue liraglutide seems to interfere in this process and may exert its beneficial effects in diabetes by affecting insulin production via restoration of ERp46 expression. PMID- 26683793 TI - A selective peroxisome proliferator-activated receptor delta agonist PYPEP suppresses atherosclerosis in association with improvement of the serum lipoprotein profiles in human apolipoprotein B100 and cholesteryl ester transfer protein double transgenic mice. AB - OBJECTIVE: Although peroxisome proliferator-activated receptor (PPAR) delta agonists have been shown to improve the serum lipoprotein profiles in humans, the impact of the changes in these lipoprotein profiles on atherosclerosis remains to be elucidated. The aim of this study was to investigate the relationship between the selective PPARdelta agonist-induced alterations of serum lipoprotein profiles and the development of atherosclerosis in human apolipoprotein B100 and cholesterol ester transfer protein double transgenic (hApoB100/hCETP-dTg) mice with human-like hypercholesterolemic dyslipidemia. METHODS: hApoB100/hCETP-dTg mice fed an atherogenic diet received a novel PPARdelta agonist (PYPEP) or vehicle for 18 weeks, followed by evaluation of atherosclerosis. Serum samples were collected during the treatment period at least at 3-week intervals to determine the lipoprotein levels and the levels of an inflammatory marker, macrophage chemotactic protein-1 (MCP-1), and to analyze the lipoprotein profile by fast protein liquid chromatography. The cholesterol efflux capacity of high density lipoprotein (HDL) was examined using [(3)H]-cholesterol labeled macrophages. RESULTS: Compared with vehicle treatment, PYPEP treatment caused increases in the serum levels of HDL cholesterol and apolipoprotein A-I (ApoA-I), as well as reductions in the serum non-HDL cholesterol and MCP-1 levels. The HDL fraction from the PYPEP-treated group maintained its cholesterol efflux capacity and showed an increased population of smaller HDL particles. PYPEP substantially suppressed atherosclerotic lesion progression, and the lesion areas had significant correlations with non-HDL cholesterol, HDL cholesterol, ApoA-I and MCP-1 by Pearson's correlation analysis. A multiple regression analysis revealed that non-HDL cholesterol and ApoA-I were significantly associated with the atherosclerotic lesion area. CONCLUSION: A novel PPARdelta agonist, PYPEP, suppressed atherosclerotic lesion progression by improving the serum lipoprotein profiles, including increased levels of ApoA-I and functional HDL particles, as well as a reduced non-HDL cholesterol level, in hApoB100/hCETP-dTg mice with human-like hypercholesterolemic dyslipidemia. PMID- 26683794 TI - Autocrine effect of vascular endothelial growth factor-A is essential for mitochondrial function in brown adipocytes. AB - OBJECTIVE: The obesity epidemic in the United States, as well as the accompanying condition of type 2 diabetes, puts a majority of the population at an increased risk of developing cardiovascular diseases including coronary artery disease, stroke, and myocardial infarction. In contrast to white adipose tissue (WAT), brown adipose tissue (BAT) is well vascularized, rich in mitochondria, and highly oxidative. While it is known that the angiogenic factor VEGF-A is required for brown adipocyte development, the functional consequences and exact mechanism remain to be elucidated. Here, we show that VEGF-A plays an essential autocrine role in the function of BAT. MATERIALS AND METHODS: Mouse models were generated with an adipose-specific and macrophage-specific ablation of VEGF-A. Adipose tissue characteristics and thermogenic response were analyzed in vivo, and mitochondrial morphology and oxidative respiration were analyzed in vitro to assess effects of endogenous VEGF-A ablation. RESULTS: VEGF-A expression levels are highest in adipocyte precursors compared to immune or endothelial cell populations within both WAT and BAT. Loss of VEGF-A in adipocytes, but not macrophages, results in decreased adipose tissue vascularization, with remarkably diminished thermogenic capacity in vivo. Complete ablation of endogenous VEGF-A decreases oxidative capacity of mitochondria in brown adipocytes. Further, acute ablation of VEGF-A in brown adipocytes in vitro impairs mitochondrial respiration, despite similar mitochondrial mass compared to controls. CONCLUSION: These data demonstrate that VEGF-A serves to orchestrate the acquisition of thermogenic capacity of brown adipocytes through mitochondrial function in conjunction with the recruitment of blood vessels. PMID- 26683795 TI - Resequencing of the CETP gene in American whites and African blacks: Association of rare and common variants with HDL-cholesterol levels. AB - BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a crucial role in lipid metabolism. Associations of common CETP variants with variation in plasma lipid levels, and/or CETP mass/activity have been extensively studied and well documented; however, the effects of uncommon/rare CETP variants on plasma lipid profile remain undefined. Hence, resequencing of the gene in extreme phenotypes and follow-up rare-variant association analyses are essential to fill this gap. OBJECTIVE: To identify common and uncommon/rare variants in the CETP gene by resequencing the entire gene and test the effects of both common and uncommon/rare CETP variants on plasma lipid traits in two genetically distinct populations. METHODS AND RESULTS: The entire CETP gene plus flanking regions were resequenced in 190 individuals comprising 95 non-Hispanic whites (NHWs) and 95 African blacks with extreme HDL-C levels. A total of 279 sequence variants were identified, of which 25 were novel. Selected variants were genotyped in the entire samples of 623 NHWs and 788 African blacks and 184 QC-passed variants were tested in relation to plasma lipid traits by using gene-based, single-site, haplotype and rare variant association analyses (SKAT-O). Two novel and independent associations of rs1968905 and rs289740 with HDL-C were identified in African blacks. Using SKAT-O analysis, we also identified rare variants with minor allele frequency <0.01 to be associated with HDL-C in both NHWs (P=0.024) and African blacks (P=0.009). CONCLUSIONS: Our results point out that in addition to the common CETP variants, rare genetic variants in the CETP gene also contribute to the phenotypic variation of HDL-C in the general population. PMID- 26683796 TI - Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. AB - Obesity is one of the major challenges for public health in 21st century, with 1.9 billion people being considered as overweight and 600 million as obese. There are certain diseases such as type 2 diabetes, hypertension, cardiovascular disease, and several forms of cancer which were found to be associated with obesity. Therefore, understanding the key molecular mechanisms involved in the pathogenesis of obesity could be beneficial for the development of a therapeutic approach. Hormones such as ghrelin, glucagon like peptide 1 (GLP-1) peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK) secreted by an endocrine organ gut, have an intense impact on energy balance and maintenance of homeostasis by inducing satiety and meal termination. Glucose and energy homeostasis are also affected by lipid sensing in which different organs respond in different ways. However, there is one common mechanism i.e. formation of esterified lipids (long chain fatty acyl CoAs) and the activation of protein kinase C delta (PKC delta) involved in all these organs. The possible role of gut microbiota and obesity has been addressed by several researchers in recent years, indicating the possible therapeutic approach toward the management of obesity by the introduction of an external living system such as a probiotic. The proposed mechanism behind this activity is attributed by metabolites produced by gut microbial organisms. Thus, this review summarizes the role of various physiological factors such as gut hormone and lipid sensing involved in various tissues and organ and most important by the role of gut microbiota in weight management. PMID- 26683797 TI - Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study. AB - BACKGROUND: Previous studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic beta-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia. METHODS: A total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. RESULTS: As serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (>=12 h, P<0.001) or near-fasting (5-11 h, P<0.001) conditions, and not in those taken under non-fasting (<5 h, P=0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (beta=0.052, P<0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA(*)glucose; beta=0.036, P<0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300 cm/s. CONCLUSIONS: Physiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature. PMID- 26683799 TI - An Overweight Preventive Score associates with obesity and glycemic traits. AB - PURPOSE: To develop a multidimensional, simple index which incorporates targeted dietary and lifestyle behaviors for the prevention and evaluation of treatment of childhood and adolescent obesity. METHODS: A total of 1072 (53.8% females) healthy children and 857 (54.8% females) adolescents from GENDAI and TEENAGE studies respectively were included in the analysis. Both studies are cross sectional, population-based studies. Dietary and lifestyle behaviors - either with negative or positive impact on obesity, based on the recommendations of Barlow and the Expert Committee - were assessed with use of two non-consecutive 24-h recalls and a dietary questionnaire. For each individual, cumulative exposures to 6 of these obesity-related behaviors, namely consumption of fruits and vegetables, breakfast and family meals, consumption of sugar sweetened beverages and fast-food meals, and screen time, were assessed through calculation of the Overweight Preventive Score. Obesity and glycemic control traits were also available for all individuals from both cohorts. RESULTS: Overweight Preventive Score was significantly associated (P<0.05) with all obesity traits and with decreased likelihood of becoming overweight [OR (95% CI): 0.90 (0.84, 0.97), P=0.003] in all individuals after adjustment for potential confounders and exclusion of low-energy reporters. Associations were also significant in stratified analyses by sex (P<0.05). The score was also associated with glycemic control traits in all individuals independently of body mass index, but these associations remained significant (P<0.05) only in males and after adjustment for potential confounders and exclusion of low-energy reporters. CONCLUSIONS: The proposed Overweight Preventive Score is a simple index and could be proven as a useful tool for the assessment of preventive and therapeutic interventions in child and adolescent overweight and insulin resistance. PMID- 26683798 TI - Metabolic health and weight: Understanding metabolically unhealthy normal weight or metabolically healthy obese patients. PMID- 26683801 TI - Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. AB - BACKGROUND: Breast cancer is the most common cancer in women worldwide and surgery, radiotherapy (RT) and chemotherapy (ChT) are frequently used to treat this cancer. Adjuvant RT has been shown to cause long-term changes in lymphocyte counts in the peripheral blood. Herein, the time course of changes in lymphocyte subpopulations upon RT was studied in patients with and without adjuvant ChT in order to explore its potential clinical impact. MATERIALS AND METHODS: Total lymphocyte counts and the composition of lymphocyte subpopulations before RT (t0), after 30 Gy (t1), at the end of RT (t2), and 6 weeks (t3), 6 months (t4), and 1 year (t5) after RT were studied by flow cytometry. RESULTS: Absolute lymphocyte counts were significantly lower in all breast cancer patients (n=40) before and also 1 year after RT compared to healthy controls. The percentage of CD3(+)/CD4(+) helper T cells and FoxP3(+) regulatory T cells increased significantly in patients without adjuvant ChT. Different NK cell subpopulations dropped during RT in patients with and without ChT, but recovered to initial levels 6months after RT (t4). During RT (t0-t2) the percentage of CD19(+) B cells significantly dropped in patients without ChT, but gradually increased in patients with adjuvant ChT. Both patient groups reached initial levels 6 months after RT (t4). CONCLUSION: Different lymphocyte subpopulations respond differently to RT with and without adjuvant ChT. CD4(+) T cells increase during RT, whereas NK cells and B cells decrease in patients without ChT, but recover within 6 months after RT. Treg cells gradually increase in patients without ChT from t0 to t5, but not in patients with adjuvant ChT. PMID- 26683800 TI - ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. AB - The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: Prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID- 26683802 TI - The Impact of Occupational Stigma on the Social Networks of Older Female Sex Workers: Results from a Three-Site Egocentric Network Study in China. PMID- 26683803 TI - Mechanistic Information from Nonstationary Points. AB - The thermal cyclization of enyne-carbodiimides substituted at both the alkyne and carbodiimide terminus showed two curved Hammett correlations (log k/k0 against sigmap) that were fully reproduced by DFT (density functional theory) computational results. The latter suggest a concerted mechanism, but the transition state (TS) analysis failed to reveal any mechanistic insight about the reason for a curved Hammett correlation. Instead a preTS inspection, i.e., examination of the electronic and steric details on route between reactant and TS, furnished a detailed picture of the mechanism. PMID- 26683804 TI - Surgically Treated Pediatric Nonpapillary Thyroid Carcinoma. AB - Introduction This study aims to update outcomes and predictors of survival on pediatric thyroid carcinoma, specifically examining pediatric patients with nonpapillary thyroid carcinoma who underwent surgical resection. Methods Surveillance, epidemiology, and end results database were searched for pediatric cases (< 20 years old) of surgically treated nonpapillary thyroid carcinoma diagnosed from 1973 to 2011. Demographics, clinical characteristics, and survival outcomes were analyzed using standard statistical methods. All follicular, medullary, Hurthle-cell, and nonencapsulated sclerosing carcinoma types were included. Results A total of 493 cases were identified. The overall incidence was 0.096/100,000 persons per year. The mean age at diagnosis was 15 years and highest incidence was found in whites, females, and patients aged 15 to 19 years. Most patients had localized (60%) or regional disease (35%) and only 38% received radiation (any type). Subtotal/total thyroidectomy was the most common procedure performed (83%) and 47% had lymph node sampling. The most common histologies were follicular (54%) and medullary (28%). Most tumors were > 2cm in size (63%). Overall 30-year survival was 91% but higher for females (94%, p = 0.02) and for local disease (92%). Disease-specific survival was highest for those with no lymph node sampling and negative lymph nodes. On multivariate analysis for medullary type only stage was an independent prognostic indicator of survival. Gender, age, tumor size, histology, and disease extent were not associated with an increased risk of mortality. Conclusions Incidence of pediatric nonpapillary thyroid cancer is low. Females have a higher incidence but similar survival to males. Stage is the only independent prognostic indicator of survival for patients with medullary thyroid cancer. PMID- 26683806 TI - Integrating Male Reproductive Health Services: One University Clinic's Story. AB - Attending a college or university opens a new chapter in a young man's life, and with it comes new experiences, freedoms, and responsibilities. Young adult males in particular are prone to risky behaviors as a result of peer pressure, and this can affect their health. As a result of this risky behavior, reproductive and sexual health could be compromised. Historically, reproductive health (RH) services have predominantly served women and undeserving men. Young men have significant reproductive health risks in the form of sexually transmitted infections (STI). Male sexual behaviors directly affect their female partners' health, and their shared decisions about reproductive health play an important part in preventing unintended pregnancies. The office of Population Affairs, Office of Family Planning (OFP), in partnership with five agencies and one research-coordinating center, has implemented a four-year comprehensive service delivery model to increase the number of males accessing family planning, reproductive health services. This paper describes the process of implementing male reproductive health services in a university clinic in western Massachusetts. The Service Innovation Model includes: 1) restructuring the clinic environment (physical setting, materials, and Internet presence), 2) staff training, and 3) campus outreach. PMID- 26683805 TI - Premature closure of a phase II study of bendamustine, mitoxantrone and rituximab for patients with untreated high-risk follicular lymphoma due to severe haematological and infectious toxicity. PMID- 26683808 TI - [Skin aging and evidence-based topical strategies]. AB - Anti-aging in dermatology primarily focuses on the prevention of skin aging with UV protection (clothing and sunsceens), free radical scavengers (synthetic or botanic), and cell-protecting agents such as vitamin B3. For the correction of signs of early skin aging, retinoic acid derivatives in dermatological prescriptions are the best studied substances. Topical hormonal prescriptions are also an option if UV damage has not been the leading culprit for aging. Chemical peeling leads to a marked increase in collagen formation, the deaper the better. Ingredients in cream preparations can reduce superficial skin folds (polyphenols, amino acid peptides). Modulators of regular pigmentation are important for anti aging preparations. Growth factors (plant extracts, recombinant growth factors) are not thoroughly studied regarding the cost-benefit and risk ratio. Complex precedures such as photodynamic therapy have an impact on the appearance of aged skin. PMID- 26683809 TI - INTERMACS profiles and modifiers: Heterogeneity of patient classification and the impact of modifiers on predicting patient outcome. AB - BACKGROUND: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles and modifiers are descriptors of patient illness severity before durable ventricular assist device implantation. It is unknown how individual U.S. institutions and practitioners assign profiles and if modifiers improve on risk discrimination. METHODS: Respondents (n = 212) to a web-based survey answered questions about the INTERMACS profile assignment process in their institution. For 5 hypothetical clinical scenarios, respondents assigned the best profile. The INTERMACS registry (2009-2014) was queried, and hazard ratio (HR) (95% confidence interval [CI]) for mortality between profiles as well as based on the presence of temporary circulatory support (TCS), frequent flyer (FF), or arrhythmia modifiers was calculated. RESULTS: Respondents included 131 (62%) cardiologists, 30 (14%) surgeons, and 51 (24%) physician extenders/coordinators. Institutional INTERMACS profile assignment was variable (63% assigned by cardiologists/surgeons; 10% by research coordinators; 27% by physician extenders). Profile assignments in hypothetical patient scenarios were heterogeneous, especially for contiguous profiles. The 1-year survivals for Profiles 1, 2, and 3 were 77 +/- 1.2%, 80 +/- 0.7%, and 84 +/- 0.7% (p < 0.001). Although Profile 1 patients had worse adjusted survival than Profile 3 patients (p = 0.001), survival for Profile 1 patients vs Profile 2 patients was similar (adjusted HR = 1.01 [95% CI = 0.88-1.12]). The TCS (adjusted HR = 1.1 [95% CI = 0.94-1.2]) and arrhythmia (adjusted HR = 1.1 [95% CI = 0.97-1.2]) modifiers were not predictive of mortality, but the FF modifier was (HR = 1.3 [95% CI = 1.02 1.63]). CONCLUSIONS: Substantial heterogeneity exists in the process and assignment of INTERMACS profiles. This heterogeneity could affect mortality estimates used for risk stratification. Only the FF modifier appears to improve risk discrimination beyond that of known risk factors. Adding objective descriptors may reduce profile heterogeneity. PMID- 26683810 TI - Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens. AB - BACKGROUND: The virtual crossmatch relies on the assignment of unacceptable antigens (UAs) to identify compatible donors. The purpose of our study was to identify an algorithm for assignment of UAs such that a negative complement dependent cytotoxicity (CDC) crossmatch and concomitant negative or weakly positive flow cytometric crossmatch (FXM) are obtained. METHODS: We used 4 antibody methods: (1) Luminex single antigen (LSA), (2) LSA with a 1:8 serum dilution, (3) C1q LSA, and (4) CDC panel. The UAs were prioritized in the following order: (1) all C1q+/CDC+, (2) LSA 1:8 >7,500 median fluorescence intensity, and (3) LSA >10,000 median fluorescence intensity. RESULTS: Of 295 heart transplants that were performed at our center, 69 (23%) recipients had detectable human leukocyte antigen specific antibody at the time of transplant. All donor specific antibodies (DSAs) were avoided for 44 of 69 (64%) (DSA-). There were 25 recipients who had DSA at the time of transplant: 12 (48%) had negative FXM (DSA+/FXM-), and 13 (52%) had positive T-cell and/or B-cell FXM (DSA+/FXM+). Lower freedom from antibody-mediated rejection was observed for the DSA+/FXM+ group compared with the DSA- group (p < 0.0001). DSA remained detectable after transplant in the sera of 14 recipients, and de novo DSA was detected in 32 recipients. Freedom from antibody-mediated rejection was comparable for both groups (p = 0.53) but was lower than the DSA- group (p < 0.0001). Survival was comparable for all groups at 1,200 days post-transplant. CONCLUSIONS: Strategic prioritization of UA assignment has allowed transplantation of highly sensitized patients across the DSA barrier with survival rates comparable to DSA- heart transplant recipients. PMID- 26683811 TI - Tissue-Specific Expression of Estrogen Receptor 1 Is Regulated by DNA Methylation in a T-DMR. AB - The mechanism controlling tissue-specific expression of estrogen receptor 1 (ESR1) is unclear. In other genes, DNA methylation of a region called the tissue dependent and differentially methylated region (T-DMR) has been associated with tissue-specific gene expression. This study investigated whether human ESR1 has a T-DMR and whether DNA methylation of the T-DMR regulates its expression. ESR1 expression was tissue-specific, being high in the endometrium and mammary gland and low/nil in the placenta and skin. Therefore, DNA methylation profiles of the promoter of ESR1 were analyzed in these tissues and in breast cancer tissues. In all of the normal tissues, the proximal promoter regions were unmethylated. On the other hand, the distal regions (T-DMR) were unmethylated in the endometrium and mammary gland, but were moderately methylated and hypermethylated in the placenta and skin, respectively. T-DMR-methylated reporter assay was performed to examine whether DNA methylation at the T-DMR suppresses ESR1 transcription. T DMR, but not the promoter region, had transcriptional activities and DNA methylation of the T-DMR suppressed ESR1 transcription. Early growth response protein 1 was shown to be a possible transcription factor to bind the T-DMR and up-regulate ESR1 expression. ESR1 has several upstream exons, and each upstream exon, Exon-A/Exon-B/Exon-C, had its own T-DMR. In some breast cancer cases and breast cancer cell lines, ESR1 expression was not regulated by DNA methylation at T-DMR as it is in normal tissues. In conclusion, ESR1 has a T-DMR. DNA methylation status at the T-DMR is involved in tissue-specific ESR1 expression in normal tissues but not always in breast cancer. PMID- 26683813 TI - Across-Time Change and Variation in Cultural Tightness-Looseness. AB - Cultural tightness-looseness, a dimension which describes the strength, multitude, and clarity of social norms in a culture, has proved significant in explaining differences between cultures. Although several studies have compared different cultures on this domain, this study is the first that targets both within-country differences and across-time variation in tightness-looseness. Using data from two nationally representative samples of Estonians, we found that the general tightness level had changed over a period of 10 years but the effect size of the change was small. A significant within country variance in 2002 had disappeared by 2012. Our results suggest that tightness-looseness, similarly to cultural value orientations, is a relatively stable and robust characteristic of culture-that is, change indeed takes place, but slowly. Future studies about across-time change and within-country variance in tightness-looseness should target more culturally diverse and socially divided societies. PMID- 26683812 TI - Alcohol Use and Transactional Sex among Women in South Africa: Results from a Nationally Representative Survey. AB - BACKGROUND: Transactional sex is a risk factor for HIV infection. Alcohol use may increase the risk of transactional sex. No nationally-representative studies have examined the relationship between multiple dimensions of alcohol use and transactional sex in women in South Africa. The aim of the study was to examine the relationship between alcohol dependence, binge drinking and frequency of drinking in the past month and transactional sex in adult women in South Africa. METHODS: A cross-sectional study using multi-stage, cluster sampling collected data from a nationally representative sample of 5,969 women aged 16-55 years in 2012. The analysis conducted for this paper was restricted to women reporting sexual activity in the past 12 months (n = 3,594). Transactional sex was defined as having received money/gifts in exchange for sex with any sex partner in the past year. Alcohol use measures included: alcohol dependence (>=2 positive responses to the CAGE questionnaire); binge drinking (>=4 drinks for women on one occasion); and drinking frequency in the previous month. Logistic regression models were built to test the hypotheses that each dimension of alcohol use was associated with transactional sex. RESULTS: About 6.3% (n = 225) of sexually active women reported transactional sex. Almost a third (30.6%) of sexually active women had ever drunk alcohol, and 19.2% were current (past month) drinkers. Among lifetime drinkers, 28.0% were alcohol dependent and 56.6% were binge drinkers. Alcohol dependent women were twice as likely to report transactional sex (AOR 2.0, 95% CI 1.1-4.3, p<0.05) than those not alcohol dependent. Binge drinkers were 3.1 times more likely to have had transactional sex (95% CI 1.5-6.6, p<0.01) than non-binge drinkers. There was no significant relationship between frequency of drinking in the past month and transactional sex. CONCLUSION: Alcohol dependency and binge drinking are significantly associated with transactional sex in South African women. HIV prevention programmes need to target these women, and address both their alcohol use, as well as the HIV risks associated with transactional sex. PMID- 26683814 TI - Large volume serial section tomography by Xe Plasma FIB dual beam microscopy. AB - Ga(+) Focused Ion Beam-Scanning Electron Microscopes (FIB-SEM) have revolutionised the level of microstructural information that can be recovered in 3D by block face serial section tomography (SST), as well as enabling the site specific removal of smaller regions for subsequent transmission electron microscope (TEM) examination. However, Ga(+) FIB material removal rates limit the volumes and depths that can be probed to dimensions in the tens of microns range. Emerging Xe(+) Plasma Focused Ion Beam-Scanning Electron Microscope (PFIB-SEM) systems promise faster removal rates. Here we examine the potential of the method for large volume serial section tomography as applied to bainitic steel and WC-Co hard metals. Our studies demonstrate that with careful control of milling parameters precise automated serial sectioning can be achieved with low levels of milling artefacts at removal rates some 60* faster. Volumes that are hundreds of microns in dimension have been collected using fully automated SST routines in feasible timescales (<24h) showing good grain orientation contrast and capturing microstructural features at the tens of nanometres to the tens of microns scale. Accompanying electron back scattered diffraction (EBSD) maps show high indexing rates suggesting low levels of surface damage. Further, under high current Ga(+) FIB milling WC-Co is prone to amorphisation of WC surface layers and phase transformation of the Co phase, neither of which have been observed at PFIB currents as high as 60nA at 30kV. Xe(+) PFIB dual beam microscopes promise to radically extend our capability for 3D tomography, 3D EDX, 3D EBSD as well as correlative tomography. PMID- 26683815 TI - GHz laser-free time-resolved transmission electron microscopy: A stroboscopic high-duty-cycle method. AB - A device and a method for producing ultrashort electron pulses with GHz repetition rates via pulsing an input direct current (dc) electron beam are provided. The device and the method are based on an electromagnetic-mechanical pulser (EMMP) that consists of a series of transverse deflecting cavities and magnetic quadrupoles. The EMMP modulates and chops the incoming dc electron beam and converts it into pico- and sub-pico-second electron pulse sequences (pulse trains) at >1GHz repetition rates, as well as controllably manipulates the resulting pulses. Ultimately, it leads to negligible electron pulse phase-space degradation compared to the incoming dc beam parameters. The temporal pulse length and repetition rate for the EMMP can be continuously tunable over wide ranges. Applying the EMMP to a transmission electron microscope (TEM) with any dc electron source (e.g. thermionic, Schottky, or field-emission source), a GHz stroboscopic high-duty-cycle TEM can be realized. Unlike in many recent developments in time-resolved TEM that rely on a sample pumping laser paired with a laser launching electrons from a photocathode to probe the sample, there is no laser in the presented experimental set-up. This is expected to be a significant relief for electron microscopists who are not familiar with laser systems. The EMMP and the sample are externally driven by a radiofrequency (RF) source synchronized through a delay line. With no laser pumping the sample, the problem of the pump laser induced residual heating/damaging the sample is eliminated. As many RF-driven processes can be cycled indefinitely, sampling rates of 1-50GHz become accessible. Such a GHz stroboscopic TEM would open up a new paradigm for in situ and in operando experiments to study samples externally driven electromagnetically. Complementary to the lower (MHz) repetition rates experiments enabled by laser photocathode TEM, new experiments in the multi-GHz regime will be enabled by the proposed RF design. Because TEM is also a platform for various analytical methods, there are infinite application opportunities in energy and electronics to resolve charge (electronic and ionic) transport, and magnetic, plasmonic and excitonic dynamics in advanced functional materials. In addition, because the beam duty-cycle can be as high as ~10(-1) (or 10%), detection can be accomplished by commercially available detectors. In this article, we report an optimal design of the EMMP. The optimal design was found using an analytical generalized matrix approach in the thin lens approximation along with detailed beam dynamics taking actual realistic dc beam parameters in a TEM operating at 200keV. PMID- 26683816 TI - Genomic, Proteomic, and Metabolite Characterization of Gemfibrozil-Degrading Organism Bacillus sp. GeD10. AB - Gemfibrozil is a widely used hypolipidemic and triglyceride lowering drug. Excess of the drug is excreted and discharged into the environment primarily via wastewater treatment plant effluents. Bacillus sp. GeD10, a gemfibrozil-degrader, was previously isolated from activated sludge. It is the first identified bacterium capable of degrading gemfibrozil. Gemfibrozil degradation by Bacillus sp. GeD10 was here studied through genome sequencing, quantitative proteomics and metabolite analysis. From the bacterial proteome of Bacillus sp. GeD10 1974 proteins were quantified, of which 284 proteins were found to be overabundant by more than 2-fold (FDR corrected p-value <=0.032, fold change (log2) >= 1) in response to gemfibrozil exposure. Metabolomic analysis identified two hydroxylated intermediates as well as a glucuronidated hydroxyl-metabolite of gemfibrozil. Overall, gemfibrozil exposure in Bacillus sp. GeD10 increased the abundance of several enzymes potentially involved in gemfibrozil degradation as well as resulted in the production of several gemfibrozil metabolites. The potential catabolic pathway/modification included ring-hydroxylation preparing the substrate for subsequent ring cleavage by a meta-cleaving enzyme. The identified genes may allow for monitoring of potential gemfibrozil-degrading organisms in situ and increase the understanding of microbial processing of trace level contaminants. This study represents the first omics study on a gemfibrozil degrading bacterium. PMID- 26683817 TI - Mechanisms of compensatory dynamics in zooplankton and maintenance of food chain efficiency under toxicant stress. AB - Communities with species that are tolerant to environmental stresses may be able to maintain the ecosystem functions under the stress, because the tolerant species can compensate for the loss of sensitive species. In this study, we focused on the food chain efficiency (FCE), the trophic transfer across three trophic levels, as an important process for ecosystem function, and examined the conditions under which such compensation could occur with aquarium experiments using an insecticide (methomyl) as the stressor. Our aquariums included one of two pairs of insecticide-tolerant and insecticide-sensitive cladoceran species, and a fish as the predator. The response of FCE to the insecticide stress, as indicated by the fish biomass production, depended on the zooplankton species combinations. FCE and total zooplankton biomass were maintained in the pair in which the compensatory changes of species abundances were clear, whereas they decreased in the pair in which the compensatory changes were not clear. This indicated the compensatory dynamics in the zooplankton community responsible for the observed resistance to the stress. We inferred the driving factors for the compensatory dynamics and the community resistance with respect to species traits of ecological importance, and concluded that a dissimilarity between species as regards the tolerance trait and a clear trade-off between the tolerance and the competitive ability was required to drive the compensatory dynamics, and a similarity or a superiority of the tolerant species as regards the functional effect trait (the predator avoidance and the reproductive potential) were required to maintain FCE. PMID- 26683818 TI - LASP-1, regulated by miR-203, promotes tumor proliferation and aggressiveness in human non-small cell lung cancer. AB - The LIM and SH3 protein 1 (LASP-1) has been reported to be associated with tumor development and progression. However, the expression and potential function of LASP-1 in human non-small cell lung cancer (NSCLC) remains undefined. Thus, this study aims to determine the relationship of LASP-1 expression with the progression and prognosis of NSCLC. Expression of LASP-1 was evaluated in NSCLC tissues and cell lines by real-time PCR, immunohistochemistry and Western blot analysis. The relationship between LASP-1 expression and clinicopathological characteristics was analyzed. The effects of LASP-1 on cell proliferation, migration and invasion were investigated in NSCLC cell lines in vitro and in vivo. Luciferase assay was used to determine whether LASP-1 could be regulated by miR-203. We found that LASP-1 was overexpressed in NSCLC and its expression level was closely correlated with tumor size, advanced TNM stage, lymph node metastasis as well as survival time and could be recognized as an independent prognostic factor of patients. LASP-1 could promote proliferation, migration and invasion of NSCLC cells in vitro and in vivo. Moreover, LASP-1 was proved to be a direct target gene for miR-203. Our results suggest that LASP-1, mediated by miR-203, has crucial functions in the proliferation, migration and invasion of NSCLC. PMID- 26683819 TI - Over-expression of nuclear NF-kappaB1 and c-Rel correlates with chemoresistance and prognosis of serous epithelial ovarian cancer. AB - OBJECTIVE: This study aims to measure the expression and subcellular location of NF-kappaB1 and c-Rel protein in serous epithelial ovarian cancer (EOC), and to test the correlation between NF-kappaB1 and c-Rel expression and clinicopathological parameters, chemoresistance, and prognosis of serous EOC. METHODS: A total of 63 specimens of serous EOC patients meeting the inclusion criteria with complete follow-up data were enrolled in our study. The specimens were divided into chemo-resistant group and sensitive group. The expression and subcellular location of NF-kappaB1 and c-Rel were assessed in paraffin sections using immunohistochemistry. The relationship between NF-kappaB1 and c-Rel protein expression and pathological characteristics of serous EOC, chemoresistance, prognosis and survival time was analyzed. RESULTS: The positive nuclear staining of NF-kappaB1 and c-Rel were significantly higher in the chemo-resistant serous EOC specimens than that in chemo-sensitive group. Lymph node metastasis and the nuclear expression of NF-kappaB1 and c-Rel were independent risk factors associated with chemotherapy resistance of serous EOC. Nucleus NF-kappaB1 and c Rel expression along with FIGO stage were independent risk factors that strongly correlated with prognosis of serous EOC. Western blot result showed the protein level of NF-kappaB1 and c-Rel was significantly higher in chemoresistant group compared with in sensitive group. CONCLUSIONS: Over-expression of nuclear NF kappaB1 and c-Rel are strong risk factors associated with chemoresistance and the prognosis of serous epithelial ovarian cancer. PMID- 26683820 TI - Equilibrium, kinetic and thermodynamic study of cesium adsorption onto nanocrystalline mordenite from high-salt solution. AB - In this study, the equilibrium, kinetics and thermodynamics of cesium adsorption by nanocrystalline mordenite were investigated under cesium contamination with high-salt solution, simulating the case of an operation and decommissioning of nuclear facilities or an accident during the processes. The adsorption rate constants were determined using a pseudo second-order kinetic model. The kinetic results strongly demonstrated that the cesium adsorption rate of nano mordenite is extremely fast, even in a high-salt solution, and much faster than that of micro mordenite. In the equilibrium study, the Langmuir isotherm model fit the cesium adsorption data of nano mordenite better than the Freundlich model, which suggests that cesium adsorption onto nano mordenite is a monolayer homogeneous adsorption process. The obtained thermodynamic parameters indicated that the adsorption involved a very stable chemical reaction. In particular, the combination of rapid particle dispersion and rapid cesium adsorption of the nano mordenite in the solution resulted in a rapid and effective process for cesium removal without stirring, which may offer great advantages for low energy consumption and simple operation. PMID- 26683821 TI - Graphene oxide as filter media to remove levofloxacin and lead from aqueous solution. AB - There is an increasing need to develop novel and high-efficiency water purification technologies. This work systematically evaluated the potential of using graphene oxide (GO) directly as filter media for the removal of levofloxacin (LEV), an emerging contaminate, and lead (Pb), a heavy metal, from aqueous solution. Batch and fixed-bed experiments were conducted to determine the sorption behaviors of LEV and Pb onto the GO. In the batch system, GO showed strong sorption of the two contaminants with Langmuir maximum adsorption capacities of 256.6 and 227.2 mg g(-1), respectively. The removal of LEV and Pb by GO in fixed-bed columns was high under all tested conditions in both single and mixed solution systems. The removal efficiency of the two contaminants in the GO-sand columns increased with increasing GO content, but decreased with increasing injection flow rate. In the mixed solution system, although LEV and Pb competed for sorption, the GO media still had high removal efficiencies for them. The column experimental data were well described by the Bed Depth Service Time (BDST) model, suggesting the model can be used for the design of GO-sand filters in large-scale applications. Findings from this work demonstrated that GO is a promising nano-adsorbent that can be used as a high-efficiency filter media in water treatment to remove hazardous metal elements and emerging contaminants. PMID- 26683822 TI - Endovascular intracranial treatment of acute ischemic strokes. AB - Acute ischemic stroke (AIS) is the leading cause of long-term disability and the second cause of death worldwide. Intravenous (IV) tissue plasminogen activator (tPA) remains the only FDA-approved treatment for AIS. The use of IV tPA in AIS related to large-vessel occlusion (LVO) has shown low recanalization rates and poor clinical outcomes. Over the last decade, endovascular treatment has demonstrated safety and effectiveness in the management of LVO-associated AIS due to the evolution of endovascular techniques and technologies, beginning with intraarterial thrombolysis, aspiration, self- expanding intracranial stents, and now retrievable stents. With the recent publication of the results of 5 randomized controlled studies, mechanical thrombectomy in combination with IV tPA demonstrated significant radiographic and clinical benefit over traditional strategies with IV tPA alone. In light of these results, endovascular therapy has been placed at the forefront of stroke treatment, redefining the standard of care. This review presents the evolution of endovascular treatment of AIS resulting from LVO; provides an analysis of the initial and latest RCTs; and discusses the association between endovascular mechanical thrombectomy and clinical outcomes, functional outcomes, and rates of revascularization, intracranial hemorrhage, morbidity, and mortality. Finally, shortcomings of the recent technological advances, such as clot fragmentation, and potential solutions to overcome these drawbacks are presented. PMID- 26683824 TI - Drug coated balloons - What is the evidence? PMID- 26683823 TI - Vein arterialization for lower limb revascularization. AB - Conventional bypass surgery is only possible when patent distal arterial outflow vessels are available. In patients with critical limb ischemia and occluded distal arteries, attempts have been made to establish retrograde perfusion through either deep or superficial pedal veins. Though historical results were disappointing, more recently limb salvage has been achieved after adopting a principle of 1) placing the anastomosis distally, and 2) actively destroying the distal valves. Experimental, para-clinical, and clinical data confirm that direct tissue nutrition is improved, angiogenesis stimulated, and collaterals opened. Only a limited number of cases have been reported in the literature and a number of different operative techniques have been described. The results in terms of limb salvage and wound healing vary widely. Generally, results are poorer than what would have been expected if femoro-distal arterial bypass had been possible. Recently, hybrid approaches have been developed to avoid extensive distal incisions by endovascular destruction of valves and closure of side branches. Also, a totally endovascular technique, including the position of a stent graft between the vein and artery, has been proposed and tested. These developments may in the future improve results by limiting incisional wound complications and make this treatment available to more patients who would otherwise have no other alternative than amputation. PMID- 26683825 TI - Synthesis of Enantiopure Piperazines via Asymmetric Lithiation-Trapping of N-Boc Piperazines: Unexpected Role of the Electrophile and Distal N-Substituent. AB - A new method for the synthesis of enantiopure alpha-substituted piperazines via direct functionalization of the intact piperazine ring is described. The approach utilizes the asymmetric lithiation-substitution of an alpha-methylbenzyl functionalized N-Boc piperazine using s-BuLi/(-)-sparteine or (+)-sparteine surrogate and provides access to a range of piperazines (as single stereoisomers). Optimization of the new methodology required a detailed mechanistic study. Surprisingly, it was found that the main culprits affecting the yield and enantioselectivity were the electrophile (the last reagent to be added to the reaction flask) and the distal N-substituent. The mechanistic studies included optimization of lithiation times using in situ IR spectroscopy, identification of a ring-fragmentation of the lithiated piperazines (that could be minimized with sterically hindered N-alkyl groups), and use of a novel "diamine switch" strategy to improve enantioselectivity with certain electrophiles. The methodology was showcased with the preparation of an intermediate for Indinavir synthesis and the stereoselective synthesis of 2,5 trans- and 2,6-trans-piperazines. PMID- 26683826 TI - Investigation into local cell mechanics by atomic force microscopy mapping and optical tweezer vertical indentation. AB - Investigating the mechanical properties of cells could reveal a potential source of label-free markers of cancer progression, based on measurable viscoelastic parameters. The Young's modulus has proved to be the most thoroughly studied so far, however, even for the same cell type, the elastic modulus reported in different studies spans a wide range of values, mainly due to the application of different experimental conditions. This complicates the reliable use of elasticity for the mechanical phenotyping of cells. Here we combine two complementary techniques, atomic force microscopy (AFM) and optical tweezer microscopy (OTM), providing a comprehensive mechanical comparison of three human breast cell lines: normal myoepithelial (HBL-100), luminal breast cancer (MCF-7) and basal breast cancer (MDA-MB-231) cells. The elastic modulus was measured locally by AFM and OTM on single cells, using similar indentation approaches but different measurement parameters. Peak force tapping AFM was employed at nanonewton forces and high loading rates to draw a viscoelastic map of each cell and the results indicated that the region on top of the nucleus provided the most meaningful results. OTM was employed at those locations at piconewton forces and low loading rates, to measure the elastic modulus in a real elastic regime and rule out the contribution of viscous forces typical of AFM. When measured by either AFM or OTM, the cell lines' elasticity trend was similar for the aggressive MDA-MB-231 cells, which were found to be significantly softer than the other two cell types in both measurements. However, when comparing HBL-100 and MCF-7 cells, we found significant differences only when using OTM. PMID- 26683827 TI - A-kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA synthesis. AB - The RNA polymerase I transcription apparatus acquires and integrates the combined information from multiple cellular signalling cascades to regulate ribosome production essential for cell growth and proliferation. In the present study, we show that a subpopulation of A-kinase anchoring protein 95 (AKAP95) targets the nucleolus during interphase and is involved in regulating rRNA production. We show that AKAP95 co-localizes with the nucleolar upstream binding factor, an essential rRNA transcription factor. Similar to other members of the C2 H2 -zinc finger family, we show, using systematic selection and evolution of ligands by exponential enrichment and in vitro binding analysis, that AKAP95 has a preference for GC-rich DNA in vitro, whereas fluorescence recovery after photobleaching analysis reveals AKAP95 to be a highly mobile protein that exhibits RNA polymerase I and II dependent nucleolar trafficking. In line with its GC-binding features, chromatin immunoprecipitation analysis revealed AKAP95 to be associated with ribosomal chromatin in vivo. Manipulation of AKAP95 expression in U2OS cells revealed a reciprocal relationship between the expression of AKAP95 and 47S rRNA. Taken together, our data indicate that AKAP95 is a novel nucleolus-associated protein with a regulatory role on rRNA production. PMID- 26683828 TI - Phylogeography of a Morphologically Cryptic Golden Mole Assemblage from South Eastern Africa. AB - The Greater Maputaland-Pondoland-Albany (GMPA) region of southern Africa was recently designated as a centre of vertebrate endemism. The phylogeography of the vertebrate taxa occupying this region may provide insights into the evolution of faunal endemism in south-eastern Africa. Here we investigate the phylogeographic patterns of an understudied small mammal species assemblage (Amblysomus) endemic to the GMPA, to test for cryptic diversity within the genus, and to better understand diversification across the region. We sampled specimens from 50 sites across the distributional range of Amblysomus, with emphasis on the widespread A. hottentotus, to analyse geographic patterns of genetic diversity using mitochondrial DNA (mtDNA) and nuclear intron data. Molecular dating was used to elucidate the evolutionary and phylogeographic history of Amblysomus. Our phylogenetic reconstructions show that A. hottentotus comprises several distinct lineages, or evolutionarily significant units (ESUs), some with restricted geographic ranges and thus worthy of conservation attention. Divergence of the major lineages dated to the early Pliocene, with later radiations in the GMPA during the late-Pliocene to early-Pleistocene. Evolutionary diversification within Amblysomus may have been driven by uplift of the Great Escarpment c. 5-3 million years ago (Ma), habitat changes associated with intensification of the east-west rainfall gradient across South Africa and the influence of subsequent global climatic cycles. These drivers possibly facilitated geographic spread of ancestral lineages, local adaptation and vicariant isolation. Our study adds to growing empirical evidence identifying East and southern Africa as cradles of vertebrate diversity. PMID- 26683829 TI - Importance of Multiple Methylation Sites in Escherichia coli Chemotaxis. AB - Bacteria navigate within inhomogeneous environments by temporally comparing concentrations of chemoeffectors over the course of a few seconds and biasing their rate of reorientations accordingly, thereby drifting towards more favorable conditions. This navigation requires a short-term memory achieved through the sequential methylations and demethylations of several specific glutamate residues on the chemotaxis receptors, which progressively adjusts the receptors' activity to track the levels of stimulation encountered by the cell with a delay. Such adaptation also tunes the receptors' sensitivity according to the background ligand concentration, enabling the cells to respond to fractional rather than absolute concentration changes, i.e. to perform logarithmic sensing. Despite the adaptation system being principally well understood, the need for a specific number of methylation sites remains relatively unclear. Here we systematically substituted the four glutamate residues of the Tar receptor of Escherichia coli by non-methylated alanine, creating a set of 16 modified receptors with a varying number of available methylation sites and explored the effect of these substitutions on the performance of the chemotaxis system. Alanine substitutions were found to desensitize the receptors, similarly but to a lesser extent than glutamate methylation, and to affect the methylation and demethylation rates of the remaining sites in a site-specific manner. Each substitution reduces the dynamic range of chemotaxis, by one order of magnitude on average. The substitution of up to two sites could be partly compensated by the adaptation system, but the full set of methylation sites was necessary to achieve efficient logarithmic sensing. PMID- 26683831 TI - PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a. AB - In secretory cells, endocytosis is coupled to exocytosis to enable proper secretion. Although endocytosis is crucial to maintain cellular homeostasis before and after secretion, knowledge about secretagogue-induced endocytosis in secretory cells is still limited. Here, we searched for proteins that interacted with the Rab27a GTPase-activating protein (GAP) EPI64 (also known as TBC1D10A) and identified the Arf6 guanine-nucleotide-exchange factor (GEF) ARNO (also known as CYTH2) in pancreatic beta-cells. We found that the insulin secretagogue glucose promotes phosphatidylinositol (3,4,5)-trisphosphate (PIP3) generation through phosphoinositide 3-kinase (PI3K), thereby recruiting ARNO to the intracellular side of the plasma membrane. Peripheral ARNO promotes clathrin assembly through its GEF activity for Arf6 and regulates the early stage of endocytosis. We also found that peripheral ARNO recruits EPI64 to the same area and that the interaction requires glucose-induced endocytosis in pancreatic beta cells. Given that GTP- and GDP-bound Rab27a regulate exocytosis and the late stage of endocytosis, our results indicate that the glucose-induced activation of PI3K plays a pivotal role in exocytosis-endocytosis coupling, and that ARNO and EPI64 regulate endocytosis at distinct stages. PMID- 26683833 TI - Imidazolium Ionic Liquids, Imidazolylidene Heterocyclic Carbenes, and Zeolitic Imidazolate Frameworks for CO2 Capture and Photochemical Reduction. AB - Imidazolium ionic liquids (ILs), imidazolylidene N-heterocyclic carbenes (NHCs), and zeolitic imidazolate frameworks (ZIFs) are imidazolate motifs which have been extensively investigated for CO2 adsorption and conversion applications. Summarized in this minireview is the recent progress in the capture, activation, and photochemical reduction of CO2 with these three imidazolate building blocks, from homogeneous molecular entities (ILs and NHCs) to heterogeneous crystalline scaffolds (ZIFs). The developments and existing shortcomings of the imidazolate motifs for their use in CO2 utilizations is assessed, with more of focus on CO2 photoredox catalysis. The opportunities and challenges of imidazolate scaffolds for future advancement of CO2 photochemical conversion for artificial photosynthesis are discussed. PMID- 26683832 TI - Sequencing of emerging canine distemper virus strain reveals new distinct genetic lineage in the United States associated with disease in wildlife and domestic canine populations. AB - BACKGROUND: Recent outbreaks of canine distemper have prompted examination of strains from clinical samples submitted to the University of Tennessee College of Veterinary Medicine (UTCVM) Clinical Virology Lab. We previously described a new strain of CDV that significantly diverged from all genotypes reported to date including America 2, the genotype proposed to be the main lineage currently circulating in the US. The aim of this study was to determine when this new strain appeared and how widespread it is in animal populations, given that it has also been detected in fully vaccinated adult dogs. Additionally, we sequenced complete viral genomes to characterize the strain and determine if variation is confined to known variable regions of the genome or if the changes are also present in more conserved regions. METHODS: Archived clinical samples were genotyped using real-time RT-PCR amplification and sequencing. The genomes of two unrelated viruses from a dog and fox each from a different state were sequenced and aligned with previously published genomes. Phylogenetic analysis was performed using coding, non-coding and genome-length sequences. Virus neutralization assays were used to evaluate potential antigenic differences between this strain and a vaccine strain and mixed ANOVA test was used to compare the titers. RESULTS: Genotyping revealed this strain first appeared in 2011 and was detected in dogs from multiple states in the Southeast region of the United States. It was the main strain detected among the clinical samples that were typed from 2011-2013, including wildlife submissions. Genome sequencing demonstrated that it is highly conserved within a new lineage and preliminary serologic testing showed significant differences in neutralizing antibody titers between this strain and the strain commonly used in vaccines. CONCLUSION: This new strain represents an emerging CDV in domestic dogs in the US, may be associated with a stable reservoir in the wildlife population, and could facilitate vaccine escape. PMID- 26683834 TI - Non-additive response of larval ringed salamanders to intraspecific density. AB - Conditions experienced in early developmental stages can have long-term consequences for individual fitness. High intraspecific density during the natal period can affect juvenile and eventually adult growth rates, metabolism, immune function, survival, and fecundity. Despite the important ecological and evolutionary effects of early developmental density, the form of the relationship between natal density and resulting juvenile phenotype is poorly understood. To test competing hypotheses explaining responses to intraspecific density, we experimentally manipulated the initial larval density of ringed salamanders (Ambystoma annulatum), a pond-breeding amphibian, over 11 densities. We modeled the functional form of the relationship between natal density and juvenile traits, and compared the relative support for the various hypotheses based on their goodness of fit. These functional form models were then used to parameterize a simple simulation model of population growth. Our data support non additive density dependence and presents an alternate hypothesis to additive density dependence, self-thinning and Allee effects in larval amphibians. We posit that ringed salamander larvae may be under selective pressure for tolerance to high density and increased efficiency in resource utilization. Additionally, we demonstrate that models of population dynamics are sensitive to assumptions of the functional form of density dependence. PMID- 26683835 TI - Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study. AB - BACKGROUND: Multiple genetic variants have been reliably associated with obesity related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. METHODS: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score--GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. RESULTS: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 * 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P(interaction) = 0.014), CADM2 rs13078960 (P(interaction) = 0.037) and GALNT10 rs7715256 (P(interaction) = 0.048) with physical activity, and PTBP2 rs11165643 (P(interaction) = 0.045), HIP1 rs1167827 (P(interaction) = 0.015), C6orf106 rs205262 (P(interaction) = 0.032) and GRID1 rs7899106 (P(interaction) = 0.043) with smoking on BMI. CONCLUSIONS: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity. PMID- 26683836 TI - Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-alpha Expression in Hydatidiform Mole and Hydropic Abortion. AB - The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-alpha immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E cadherin, p53, and inhibin-alpha protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n = 23), PHM (n = 24), and CHM (n = 23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-alpha expression in all cases. E cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-alpha was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-alpha expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM. PMID- 26683837 TI - Mutation Scanning of D1705 and D1709 in the RNAse IIIb Domain of MicroRNA Processing Enzyme Dicer in Cutaneous Melanoma. AB - Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metal-ion-binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain. PMID- 26683838 TI - The Independent Evolution Method Is Not a Viable Phylogenetic Comparative Method. AB - Phylogenetic comparative methods (PCMs) use data on species traits and phylogenetic relationships to shed light on evolutionary questions. Recently, Smaers and Vinicius suggested a new PCM, Independent Evolution (IE), which purportedly employs a novel model of evolution based on Felsenstein's Adaptive Peak Model. The authors found that IE improves upon previous PCMs by producing more accurate estimates of ancestral states, as well as separate estimates of evolutionary rates for each branch of a phylogenetic tree. Here, we document substantial theoretical and computational issues with IE. When data are simulated under a simple Brownian motion model of evolution, IE produces severely biased estimates of ancestral states and changes along individual branches. We show that these branch-specific changes are essentially ancestor-descendant or "directional" contrasts, and draw parallels between IE and previous PCMs such as "minimum evolution". Additionally, while comparisons of branch-specific changes between variables have been interpreted as reflecting the relative strength of selection on those traits, we demonstrate through simulations that regressing IE estimated branch-specific changes against one another gives a biased estimate of the scaling relationship between these variables, and provides no advantages or insights beyond established PCMs such as phylogenetically independent contrasts. In light of our findings, we discuss the results of previous papers that employed IE. We conclude that Independent Evolution is not a viable PCM, and should not be used in comparative analyses. PMID- 26683839 TI - Life-threatening pleural hemorrhage following intrapleural enzyme therapy and successful treatment with fibrin-thrombin sealant pleurodesis: a case report. AB - INTRODUCTION: Intrapleural fibrinolytic enzyme therapy is a potentially surgery sparing treatment for poorly resolving parapneumonic effusion and empyema. It is safe in the majority of patients, however the most significant risk associated with this treatment is severe bleeding secondary to pleural hemorrhage. Contraindications for intrapleural enzyme therapy are not widely agreed upon and little is known about how to treat this difficult and potentially lethal hemorrhagic complication. CASE PRESENTATION: An independent 82-year-old Caucasian man presented to hospital with an empyema complicating community-acquired pneumonia and coincidental pulmonary embolus. He was initially commenced on intravenous antibiotics, pleural drainage and anticoagulation, however failed to improve significantly and was commenced on intrapleural fibrinolytic enzyme therapy. Shortly after, he suffered severe pleural hemorrhage that was uncontrollable despite emergency thoracotomy and washout. Subsequent hemostasis was achieved after re-exploration and application of topical fibrin-thrombin sealant spray. The patient survived and was discharged home. CONCLUSIONS: Intrapleural enzyme therapy can be effective in loculated parapneumonic effusion and empyema, but massive pleural hemorrhage can complicate its use. Pleural hemorrhage appears to be associated with anticoagulation or coagulopathy, and can be difficult to manage. This case adds to the body of data on bleeding complications following intrapleural enzyme therapy, and to the best of our knowledge is the first report of fibrin-thrombin sealant use in this setting. PMID- 26683840 TI - Does it matter whose opinion we seek regarding the allocation of healthcare resources? - a case study. AB - BACKGROUND: Societal preferences have to be taken into consideration to ensure difficult healthcare decisions are legitimate and acceptable. It has been interesting to ascertain whether attitudes towards the principles of public healthcare resources allocation are homogenous. In particular, it has been thought provoking to ask whether advancement in medical technologies, and growing accessibility issues due to scarcity of healthcare resources, have influenced the beliefs of the general public with regard to allocative principles in recent years. The objective of this study was to compare preferences towards the distribution of healthcare resources between younger and older members of society. METHODS: Discrete choice experiments using the equivalence of numbers technique and the social welfare function were conducted in Poland. Public preferences towards disease severity, and potential to benefit, as well as aversion to inequity, were elicited. In order to ensure full understanding of questions by the older respondents, a pilot study with ten respondents aged 65+ was conducted. RESULTS: In total, 52 adult respondents (seniors) and 45 students (juniors) were interviewed. While the first were unwilling to trade between different patients, the latter chose a higher number of individuals to compensate for the loss of ten patients with a more severe disease and a higher potential to treat everything else being equal. Juniors were more inequality averse compared to seniors as well. CONCLUSIONS: While the revealed preferences of seniors were egalitarian, juniors were more willing to differentiate between disease severity and potential to benefit. Differences in opinion between juniors and seniors should be considered in open dialogue regarding healthcare rationing. Insight into the preferences towards health maximization of the former group and the egalitarian beliefs of the latter group could be useful for decision makers in the search for public acceptance of allocation of scarce healthcare resources. PMID- 26683841 TI - Ecology and spatiotemporal dynamics of sandflies in the Mediterranean Languedoc region (Roquedur area, Gard, France). AB - BACKGROUND: Phlebotomine sandflies are hematophagous insects widely present in Western Mediterranean countries and known for their role as Leishmania vectors. During the last ten years, the risk of leishmaniasis re-emergence has increased in France. However, sandfly biology and ecology in the South of France remain poorly known because the last detailed study on their spatiotemporal dynamics was performed over 30 years ago. The aim of the present study was to update our knowledge on sandfly ecology by determining their spatiotemporal dynamics and by investigating the relationship between environmental/climatic factors and the presence and abundance of sandflies in the South of France. METHODS: An entomological survey was carried out during three years (2011-2013) along a 14 kilometer-long transect. The findings were compared with the data collected along the same transect in 1977. Data loggers were placed in each station and programmed to record temperature and relative humidity every six hours between April 2011 and November 2014. Several environmental factors (such as altitude, slope and wall orientation (North, East, West and South)) were characterized at each station. RESULTS: Four sandfly species were collected: Phlebotomus ariasi and Sergentomyia minuta, which were predominant, Ph. perniciosus and Ph. mascittii. Sandfly activity within the studied area started in May and ended in October with peaks in July-August at the optimum average temperature. We found a positive effect of altitude and temperature and a negative effect of relative humidity on Ph. ariasi and Se. minuta presence. We detected interspecific differences and non-linear effects of these climatic variables on sandfly abundance. Although the environment has considerably changed in 30 years, no significant difference in sandfly dynamics and species diversity was found by comparing the 1977 and 2011-2013 data. CONCLUSION: Our study shows that this area maintains a rich sandfly fauna with high Ph. ariasi population density during the active season. This represents a risk for Leishmania transmission. The analysis revealed that the presence and abundance of Ph. ariasi and Se. minuta were differently correlated with the environmental and climatic factors. Comparison with the data collected in 1977 highlighted the sandfly population stability, suggesting that they can adapt, in the short and long term, to changing ecosystems. PMID- 26683842 TI - Partnering with parents to disclose Klinefelter syndrome to their child. AB - In paediatrics, a diagnosis of Klinefelter syndrome can occur after prenatal testing or because of symptoms such as learning difficulties or incomplete puberty. After the diagnosis, parents have to decide when and how to speak about this condition to their child. Parents and healthcare professionals (HCPs) may have different perceptions related to disclosure of this diagnosis. Due to the absence of clear guidelines, parents and HCPs may feel uncomfortable discussing the condition and may hide the truth in a prolonged fashion. CONCLUSION: For patients with a prenatal diagnosis, we recommend a gradual and personalised disclosure process starting between the ages of 5 and 13 years. For older patients, a personalised approach should also be the goal. Various communication strategies and recommendations regarding disclosure of Klinefelter syndrome are proposed. PMID- 26683843 TI - UK's approval of mitochondrial donation shows how decisions on gene editing can be made. PMID- 26683844 TI - High-frequency pulsed ENDOR spectroscopy of the NV(-) centre in the commercial HPHT diamond. AB - This work reports direct 94GHz ENDOR spectroscopy of the (14)N nuclei in the NV( ) centre in single-crystal diamond. Roadmaps of ENDOR frequencies were measured and hyperfine/quadrupole interaction parameters were obtained, with AX,Y=-2.7MHz, AZ=-2.2MHz and P=-4.8MHz. The sign and value of each parameter was calculated using spin Hamiltonian matrix diagonalization, first and second order perturbation theory and confirmed experimentally. Magnetic field magnitude was measured by (13)C ENDOR signal with 0.02% precision or 0.5mT. The orientation of quadrupole, hyperfine and fine structure tensors are the same within error of experiment, g-factor is isotropic. PMID- 26683845 TI - Childhood trauma and treatment outcome in bipolar disorder. AB - The aim of the present study was to investigate the potential influence of childhood trauma on clinical presentation, psychiatric comorbidity, and long-term treatment outcome of bipolar disorder. A total of 135 consecutive patients with bipolar disorder type I were recruited from an ongoing prospective follow-up project. The Childhood Trauma Questionnaire and the Structured Clinical Interview for DSM-IV Axis I Disorders were administered to all participants. Response to long-term treatment was determined from the records of life charts of the prospective follow-up project. There were no significant differences in childhood trauma scores between groups with good and poor responses to long-term lithium treatment. Poor responders to long-term anticonvulsant treatment, however, had elevated emotional and physical abuse scores. Lifetime diagnosis of posttraumatic stress disorder (PTSD) was associated with poor response to lithium treatment and antidepressant use but not with response to treatment with anticonvulsants. Total childhood trauma scores were related to the total number of lifetime comorbid psychiatric disorders, antidepressant use, and the presence of psychotic features. There were significant correlations between all types of childhood abuse and the total number of lifetime comorbid psychiatric diagnoses. Whereas physical neglect was related to the mean severity of the mood episodes and psychotic features, emotional neglect was related to suicide attempts. A history of childhood trauma or PTSD may be a poor prognostic factor in the long-term treatment of bipolar disorder. Whereas abusive experiences in childhood seem to lead to nosological fragmentation (comorbidity), childhood neglect tends to contribute to the severity of the mood episodes. PMID- 26683847 TI - Solvent Viscosity Effect on Triplet-Triplet Pair in Triplet Fusion. AB - The effect of the solvent viscosity dependence of time-resolved magnetoluminescence (ML) on the delayed fluorescence of 9,10-diphenylanthracene (DPA) sensitized by platinum octaethylporphyrin has clarified the structure and dynamics of the triplet-triplet pair (TT), i.e., the transition state of triplet fusion. Phase inversion of the ML effect with time provides evidence for the recycle dynamics of the excited triplet state for DPA in triplet fusion. The electron spin-relaxation by random molecular rotation causes intersystem crossing among the different spin states of the triplet-triplet pair and allows the (3,5)TT to engage in triplet fusion. Therefore, slow-down of the molecular diffusion by an increase in the solvent viscosity can enhance the triplet fusion yield. However, the reduction of the ML effect observed in quite high viscosity solvents suggests that the substantially slow rotational motion decreases the triplet fusion yield due to steric factors in electron exchange from the triplet triplet pair. PMID- 26683846 TI - Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination. AB - Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases. PMID- 26683849 TI - Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods. AB - In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity. A non-invasive measurement of both elements could therefore be of potential interest. The main aim of this current study was to evaluate and compare the performance of an upgraded portable XRF system and an advanced version of the benchtop XRF system for both selenium and arsenic. This evaluation was performed in terms of arsenic and selenium Kalpha detection limits for a 4W gold anode Olympus InnovX Delta portable analyzer (40 kVp) in polyester resin skin-mimicking phantoms. Unlike the polychromatic source earlier reported in the literature, the benchtop tube-based technique involves monochromatic excitation (25 W silver anode, manufactured by x ray optics, XOS) and a higher throughput detector type. Use of a single exciting energy allows for a lower in vivo dose delivered and superior signal-noise ratio. For the portable XRF method, arsenic and selenium minimum detection limits (MDLs) of 0.59 +/- 0.03 ppm and 0.75 +/- 0.02 ppm respectively were found for 1 min measurement times. The MDLs for arsenic and selenium using the benchtop system were found to be 0.35 +/- 0.01 ppm and 0.670 +/- 0.004 ppm respectively for 30 min measurement times. In terms of a figure of merit (FOM), allowing for dose as well as MDL, the benchtop system was found to be superior for arsenic and the two systems were equivalent, within error, for selenium. We shall discuss the performance and possible improvements of each system, their ease of use and potential for field application. PMID- 26683848 TI - Substrate stiffness effect and chromosome missegregation in hIPS cells. AB - BACKGROUND: Ensuring genetic stability in pluripotent stem cell (PSC) cultures is essential for the development of successful cell therapies. Although most instances lead to failed experiments and go unreported in the literature, many laboratories have found the emergence of genetic abnormalities in PSCs when cultured in vitro for prolonged amounts of time. These cells are primarily cultured in non-physiological stiff substrates like tissue culture polystyrene (TCPS) which raises the possibility that the cause of these abnormalities may be influenced by substrate mechanics. FINDINGS: In order to investigate this, human PSCs were grown on substrates of varying stiffness such as a range of polyacrylamide formulations, TCPS, and borosilicate glass coverslips. These substrates allowed for the testing of a stiffness range from 5kPa to 64GPa. Two human induced PSC (iPSC) lines were analyzed in this study: 19-9-11 iPSCs and 19.7 clone F iPSCs. Centrosome and DNA staining revealed that 19-9-11 iPSCs range from 1-8.5 % abnormal mitoses under the different culture conditions. A range of 4.4-8.1 % abnormal mitoses was found for 19.7 clone F iPSCs. CONCLUSIONS: Abnormal cell division was not biased towards one particular substrate. It was confirmed by Analysis of Variance (ANOVA) and Tukey's Honest Significant Difference test that there was no statistically significant difference between passage numbers, cell lines, or substrates. PMID- 26683850 TI - Tele-Derm National: A decade of teledermatology in rural and remote Australia. AB - OBJECTIVE: To identify the current scope of Tele-Derm, the types of dermatological complaints experienced in the rural primary care setting, and to assess the quality of patient clinical information provided to the consultant dermatologist. DESIGN: Retrospective case analysis. SETTING: Tele-Derm National is an initiative of the Australian College of Rural and Remote Medicine and has been providing online educational and consultational services in dermatology to doctors Australia-wide for over a decade. PARTICIPANTS: Patient cases that were submitted to Tele-Derm for specialist dermatologist advice. INTERVENTIONS: Audit of submitted cases. MAIN OUTCOME MEASURES: The types of patient presentations and reason for submission for specialist opinion were analysed. The quality of clinical information provided was also evaluated. RESULTS: A total of 406 cases submitted over 2012-2013 were analysed. Most patients were from the outpatient setting with 'rash' or dermatitis (66%). Almost one-third of patients were paediatric cases. The average time from submission to dermatologist reply was 5.5 hours. Clinical photos were provided in 83% of cases and 73% of these were assessed as being of good quality. Management advice was provided in 77% of cases, of which reference to the case-based learning modules on Tele-Derm was made in 21% of cases. Patient outcome was largely unknown (83%). CONCLUSION: This study identified some of the common dermatological complaints presenting to rural and remote primary care doctors in Australia. The unique addition of professional development in Tele-Derm can be used as an adjunct to advice provided to the rural doctors seeking advice for patient management. PMID- 26683851 TI - Aortic Elastic Properties and Myocardial Performance Index Are Impaired in Patients with Lichen Planus. AB - OBJECTIVES: The aim of this study was to investigate the elastic properties of the aorta and the myocardial performance index of the left ventricle (LV) in patients with lichen planus (LP). SUBJECTS AND METHODS: A total of 54 patients with LP and 50 controls were enrolled in the study. The 2 groups were well matched regarding age, gender, body mass index, any smoking history, diabetes mellitus and systolic and diastolic blood pressure (SBP and DBP). The echocardiographic examination was performed on the study subjects and the controls. Aortic elasticity parameters and the myocardial performance index of the LV were calculated. The Student t test, the x03C7;2 test and multiple linear regression were used for the statistical analysis. RESULTS: Aortic strain (AS, 4.77 +/- 1.81 vs. 8.95 +/- 2.22; p < 0.001) and aortic distensibility (AD, 0.25 +/- 0.009 vs. 0.42 +/- 0.120; p < 0.001) were significantly lower, and aortic stiffness index beta (ASIbeta, 3.65 +/- 1.03 vs. 2.70 +/- 0.91; p < 0.001) was significantly higher in the LP group than in the controls. The myocardial performance index (Tei index) was significantly higher in the LP group than in the control group (p = 0.001). The duration of the LP was negatively correlated with AS (r = -0.364, p < 0.001) and AD (r = -0.279, p = 0.006), and positively correlated with the Tei index (r = 0.324, p = 0.001) and ASIbeta (r = 0.364, p < 0.001). After adjustment for relevant confounders (age, male gender, smoking, SBP, DBP, diabetes mellitus and low- and high-density lipoprotein cholesterol), LP and its duration were still associated with AS, AD and ASIbeta. CONCLUSION: In this study, AS and AD were lower and ASIbeta and myocardial performance index higher in LP patients than in controls. PMID- 26683867 TI - Unmet Needs at the Time of Emergency Department Discharge. AB - OBJECTIVES: Emergency department (ED) discharge requires conveying critical information in a time-limited and distracting setting. Limited health literacy may put patients at risk of incomplete comprehension, but the relationship between discharge communication needs and health literacy has not been well defined. The goal of this study was to characterize the variation in needs and preferences regarding the ED discharge process by health literacy and identify novel ideas for process improvement from parents and patients. METHODS: This was an in-depth qualitative interview study in two EDs using asthma as a model system for health communication. Adult patients and parents of pediatric patients with an asthma exacerbation and planned discharge were enrolled using purposive sampling to balance across literacy groups at each site. Interviews were audiotaped, transcribed, coded independently by two team members, and analyzed using a modified grounded theory approach. Interviews were conducted until thematic saturation was reached in both literacy groups at each site. RESULTS: In depth interviews were completed with 51 participants: 20 adult patients and 31 pediatric parents. The majority of participants identified barriers related to ED providers, such as use of medical terminology, and systems of care, such as absence of protected time for discharge communication. Patients with limited health literacy, but not those with adequate literacy, identified conflicting information between health care sources as a barrier to successful ED discharge. CONCLUSIONS: Participants across literacy groups and settings identified multiple actionable areas for improvement in the ED discharge process. These included the use of simplified/lay language, increased visual learning and demonstration, and the desire for complete information. Individuals with limited literacy may particularly benefit from increased attention to consistency. PMID- 26683868 TI - Synthesis of Oxazolidin-2-ones by Oxidative Coupling of Isonitriles, Phenyl Vinyl Selenone, and Water. AB - Reaction of alkyl isocyanides, phenyl vinyl selenone, and water in the presence of a catalytic amount of Cs2 CO3 afforded oxazolidin-2-ones in good yields. This unprecedented heteroannulation process created four chemical bonds in a single operation with the isocyano group acting formally as a polarized double bond and phenyl vinyl selenone as a latent 1,3-dipole. The phenylselenonyl group played a triple role as an electron-withdrawing group to activate the 1,4-addition, a leaving group, and a latent oxidant in this transformation. PMID- 26683869 TI - Concise Review: Patient-Specific Stem Cells to Interrogate Inherited Eye Disease. AB - Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease. With the advent of patient-specific induced pluripotent stem cells (iPSCs), researchers are now able to obtain disease-specific cell types that would otherwise be unavailable for molecular analysis. In the present review, we discuss how the iPSC technology is being used to confirm the pathogenesis of novel genetic variants, interrogate the pathophysiology of disease, and accelerate the development of patient-centered treatments. Significance: Stem cell technology has created the opportunity to advance treatments for multiple forms of blindness. Researchers are now able to use a person's cells to generate tissues found in the eye. This technology can be used to elucidate the genetic causes of disease and develop treatment strategies. In the present review, how stem cell technology is being used to interrogate the pathophysiology of eye disease and accelerate the development of patient-centered treatments is discussed. PMID- 26683870 TI - Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease. AB - An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical and clinical studies have shown paradoxical results, with inconsistent findings regarding the relationship between the cell dose and clinical benefit. Such phenomena can, at least in part, be attributed to variations in cell dosing or concentration and the route of administration (ROA). Although clinical trials of cell-based therapy for cardiovascular disease began more than a decade ago, specification of the optimal dosage and ROA has not been established. The present review summarizes what has been learned regarding the optimal cell dosage and ROA from preclinical and clinical studies of stem cell therapy for heart disease and offers a perspective on future directions. Significance: Preclinical and clinical studies on cell-based therapy for cardiovascular disease have shown inconsistent results, in part because of variations in study-specific dosages and/or routes of administration (ROA). Future preclinical studies and smaller clinical trials implementing cell-dose and ROA comparisons are warranted before proceeding to pivotal trials. PMID- 26683871 TI - Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-beta Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation. AB - Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-beta type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic screens are discussed, demonstrating the value of this biologically relevant and reproducible technology. In addition, this assay system was able to identify novel and potent inducers of differentiation and proliferation of induced pluripotent stem cell-derived cardiac progenitor cells. PMID- 26683872 TI - Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog. AB - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3beta activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3beta; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3beta activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. PMID- 26683874 TI - Differences in body posture, strength and flexibility in schoolchildren with overweight and obesity: A quasi-experimental study. AB - BACKGROUND: Body posture and its components have been widely discussed, given the high prevalence of musculoskeletal disorders in children and adolescents. Among children and adolescents with overweight and obesity issues, these changes can be pronounced. OBJECTIVES: This study sought to investigate whether a global exercise routine could result in positive changes in the angles and distances measured in postural assessments and in the number of abdominal and flexibility exercise repetitions performed by children and adolescents with overweight or obesity. METHODS: A quasi-experimental design including an experimental group (EG) and a control group (CG) was used. The primary outcome variables included ratings of body posture (using SAPO software) and measures of abdominal muscle strength (number of sit-ups) and flexibility. The EG received an interdisciplinary intervention the included 48 sessions of global postural exercises performed three times a week. RESULTS: Of the 46 schoolchildren evaluated (EG, n = 23 and CG, n = 23), significant changes were observed in the EG from pre-to post-test in the thoracic angle (p = 0.001) and abdominal muscle strength (p = 0.016) for boys and in the thoracic angle (p = 0.010), abdominal muscle strength (p = 0.003) and flexibility (p = 0.010) for girls. CONCLUSIONS: Overall, the exercise program led to changes in the angle and distance measurements obtained in postural evaluations and contributed to increases in the number of repetitions of abdominal and flexibility exercises, indicating improvements in the EG group's body posture and health indicators. PMID- 26683873 TI - Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice. AB - Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the fat tissue origin-dependent differences in AdSC function and differentiation potential. AdSC rich cells were isolated from subcutaneous, visceral, cardiac (CA), and subscapular adipose tissue from mice and their characteristics analyzed. After four different AdSC types were cultured with specific differentiation medium, immunocytochemical analysis was performed for the assessment of differentiation into cardiovascular cells. We then examined the in vitro differentiation capacity and therapeutic potential of AdSCs in ischemic myocardium using a mouse myocardial infarction model. The cell density and proliferation activity of CA derived AdSCs were significantly increased compared with the other adipose tissue derived AdSCs. Immunocytochemistry showed that CA-derived AdSCs had the highest appearance rates of markers for endothelial cells, vascular smooth muscle cells, and cardiomyocytes among the AdSCs. Systemic transfusion of CA-derived AdSCs exhibited the highest cardiac functional recovery after myocardial infarction and the high frequency of the recruitment to ischemic myocardium. Moreover, long-term follow-up of the recruited CA-derived AdSCs frequently expressed cardiovascular cell markers compared with the other adipose tissue-derived AdSCs. Cardiac adipose tissue could be an ideal source for isolation of therapeutically effective AdSCs for cardiac regeneration in ischemic heart diseases. Significance: The present study found that cardiac adipose-derived stem cells have a high potential to differentiate into cardiovascular lineage cells (i.e., cardiomyocytes, endothelial cells, and vascular smooth muscle cells) compared with stem cells derived from other adipose tissue such as subcutaneous, visceral, and subscapular adipose tissue. Notably, only a small number of supracardiac adipose-derived stem cells that were systemically transplanted sufficiently improved cardiac functional recovery after myocardial infarction, differentiating into cardiovascular cells in the ischemic myocardium. These findings suggest a new autologous stem cell therapy for patients with myocardial ischemia, especially those with secondary myocardial ischemia after cardiovascular open chest surgery. PMID- 26683875 TI - Intestinal transplantation: The anesthesia perspective. AB - Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis, drug interactions between anesthetic and immunosuppressive agents and venous access are some of the anesthetic considerations for this group. PMID- 26683876 TI - Portuguese Lexical Clusters and CVC Sequences in Speech Perception and Production. AB - This paper investigates similarities between lexical consonant clusters and CVC sequences differing in the presence or absence of a lexical vowel in speech perception and production in two Portuguese varieties. The frequent high vowel deletion in the European variety (EP) and the realization of intervening vocalic elements between lexical clusters in Brazilian Portuguese (BP) may minimize the contrast between lexical clusters and CVC sequences in the two Portuguese varieties. In order to test this hypothesis we present a perception experiment with 72 participants and a physiological analysis of 3-dimensional movement data from 5 EP and 4 BP speakers. The perceptual results confirmed a gradual confusion of lexical clusters and CVC sequences in EP, which corresponded roughly to the gradient consonantal overlap found in production. PMID- 26683877 TI - Long-Acting Growth Hormone: An Update. AB - After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field. PMID- 26683878 TI - Controlling the rheology of gellan gum hydrogels in cell culture conditions. AB - Successful culturing of tissues within polysaccharide hydrogels is reliant upon specific mechanical properties. Namely, the stiffness and elasticity of the gel have been shown to have a profound effect on cell behaviour in 3D cell cultures and correctly tuning these mechanical properties is critical to the success of culture. The usual way of tuning mechanical properties of a hydrogel to suit tissue engineering applications is to change the concentration of polymer or its cross-linking agents. In this study sonication applied at various amplitudes was used to control mechanical properties of gellan gum solutions and gels. This method enables the stiffness and elasticity of gellan gum hydrogels cross-linked with DMEM to be controlled without changing either polymer concentration or cross linker concentration. Controlling the mechanical behaviour of gellan hydrogels impacted upon the activity of alkaline phosphatase (ALP) in encapsulated MC3T3 pre-osteoblasts. This shows the potential of applying a simple technique to generate hydrogels where tissue-specific mechanical properties can be produced that subsequently influence cell behaviour. PMID- 26683879 TI - Effects of macromolecular crowding and osmolyte on human Tau fibrillation. AB - Tau fibrillation is reported to be involved in neurodegenerative disorders, such as Alzheimer's disease, in which the natural environment is very crowded in the cells. Understanding the role of crowding environments in regulating Tau fibrillation is of great importance for elucidating the etiology of these diseases. In this experiment, the effects of macromolecular crowding and osmolyte reagents in the crowding environment on Tau fibrillation were studied by thioflavin T binding, SDS-PAGE and TEM assays. Ficoll 70 and Dextran 70 of different concentrations were used as macromolecular crowding reagents inside the cells and showed a strong enhancing effect on the fibrillation of normal and hyperphosphorylated Tau. The enhancing effect of Dextran is stronger than that of Ficoll 70 at the same concentration. In addition, the cellular osmolyte sucrose was found to protect Tau against fibrillation, and inhibit the enhancing effect of macromolecular crowding on Tau fibrillation. A possible model for the fibrillation process of Tau and the effect of macromolecular crowding and osmolyte on this process was proposed based on these experimental results. The information obtained from our study can enhance the understanding of how proteins aggregate and avoid aggregation in crowded physiological environments and might lead to a better understanding of the molecular mechanisms of Alzheimer's disease in vivo. PMID- 26683880 TI - Comparative investigation of the binding characteristics of poly-L-lysine and chitosan on alginate hydrogel. AB - The binding properties of poly-L-lysine and chitosan to alginate have been evaluated quantitatively and compared. Poly-L-lysine bound to alginate hydrogel more rapidly than chitosan as poly-L-lysine has a smaller molar hydrodynamic volume. In addition, poly-L-lysine showed a much higher binding capacity (6.14:1) for alginate hydrogel beads than chitosan (2.71:1), and a little higher binding stoichiometry (0.58) to sodium alginate molecules in solution than chitosan (0.49). An exothermic heat of alginate-poly-L-lysine complexes formation of 2.02 kJ/mol was detected. For alginate-chitosan complexes, the binding enthalpy has been seen to be -3.49 kJ/mol. The stability of the polyelectrolyte complexes was related to their binding enthalpy. The alginate-poly-L-lysine complexes could be disintegrated and rebuilt. By contrast, chitosan was bound with alginate in a steady state. These results provide fundamental insights regarding the structure and property relationships of macromolecules, and will be helpful in designing and selecting appropriate polymers. PMID- 26683881 TI - Development of Highly Potent GAT1 Inhibitors: Synthesis of Nipecotic Acid Derivatives by Suzuki-Miyaura Cross-Coupling Reactions. AB - A new series of potent and selective mGAT1 inhibitors has been identified, featuring a nipecotic acid residue and an N-butenyl linker with a 2-biphenyl residue at the omega-position. Docking, combined with MD calculations, revealed a binding mode for the new compounds similar to that of tiagabine, the only mGAT1 inhibitor currently approved as antiepileptic drug. For the synthesis, a Suzuki Miyaura cross-coupling reaction was used as a key step by which variously substituted biaryl subunits were assembled. Biological evaluation revealed several compounds that possess binding affinities and inhibitory potencies toward mGAT1, together with subtype selectivities against mGAT2-mGAT4 that were similar to or even higher than those for tiagabine. A derivative carrying the 2',4' dichloro-2-biphenyl moiety attached to N-but-3-enylnipecotic acid at the terminal position of the linker chain was found to be the most potent binder, with the racemic form of the compound displaying a binding affinity of 8.05+/-0.13 (pKi ), while the R enantiomer exhibited an affinity value of 8.33+/-0.06 (pKi ). PMID- 26683882 TI - Is acute stress and plasminogen activator inhibitor polymorphism associated with acute ischemic stroke? PMID- 26683883 TI - Pancreatic guidewire technique increases the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. PMID- 26683884 TI - How to improve the quality of evidence when new treatments are funded conditional on collecting evidence of effectiveness and safety. PMID- 26683885 TI - Using institutional theory to analyse hospital responses to external demands for finance and quality in five European countries. AB - OBJECTIVES: Given the impact of the global economic crisis, delivering better health care with limited finance grows more challenging. Through the lens of institutional theory, this paper explores pressures experienced by hospital leaders to improve quality and constrain spending, focusing on how they respond to these often competing demands. METHODS: An in-depth, multilevel analysis of health care quality policies and practices in five European countries including longitudinal case studies in a purposive sample of ten hospitals. RESULTS: How hospitals responded to the financial and quality challenges was dependent upon three factors: the coherence of demands from external institutions; managerial competence to align external demands with an overall quality improvement strategy, and managerial stability. Hospital leaders used diverse strategies and practices to manage conflicting external pressures. CONCLUSIONS: The development of hospital leaders' skills in translating external requirements into implementation plans with internal support is a complex, but crucial, task, if quality is to remain a priority during times of austerity. Increasing quality improvement skills within a hospital, developing a culture where quality improvement becomes embedded and linking cost reduction measures to improving care are all required. PMID- 26683886 TI - A Tube Seepage Meter for In Situ Measurement of Seepage Rate and Groundwater Sampling. AB - We designed and evaluated a "tube seepage meter" for point measurements of vertical seepage rates (q), collecting groundwater samples, and estimating vertical hydraulic conductivity (K) in streambeds. Laboratory testing in artificial streambeds show that seepage rates from the tube seepage meter agreed well with expected values. Results of field testing of the tube seepage meter in a sandy-bottom stream with a mean seepage rate of about 0.5 m/day agreed well with Darcian estimates (vertical hydraulic conductivity times head gradient) when averaged over multiple measurements. The uncertainties in q and K were evaluated with a Monte Carlo method and are typically 20% and 60%, respectively, for field data, and depend on the magnitude of the hydraulic gradient and the uncertainty in head measurements. The primary advantages of the tube seepage meter are its small footprint, concurrent and colocated assessments of q and K, and that it can also be configured as a self-purging groundwater-sampling device. PMID- 26683887 TI - Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion. AB - BACKGROUND AND OBJECTIVES: The urinary excretion of uromodulin is influenced by common variants in the UMOD gene, and it may be related to NaCl retention and hypertension. Levels of uromodulin are also dependent of the renal function, but other determinants remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested associations between the urinary excretion of uromodulin; medical history and medication; serum and urinary levels of electrolytes, glucose, and uric acid; and the genotype at the UMOD/Protein Disulfide Isomerase-Like, Testis Expressed locus (rs4293393 and rs12446492); 943 participants from the CARTaGENE Cohort, a random sample from the Canadian population of 20,004 individuals, were analyzed. Participants with available genotyping were obtained from a substudy addressing associations between common variants and cardiovascular disease in paired participants with high and low Framingham risk scores and vascular rigidity indexes. RESULTS: The population studied was 54+/-9 years old, with 51% women and eGFR of 9+/-14 ml/min per 1.73 m(2). Uromodulin excretion was 25 (11 42) mg/g creatinine. Using linear regression, it was independently higher among patients with higher eGFR, the TT genotype of rs4293393, and the TT genotype of rs12446492. The fractional excretions of urate and sodium showed a strong positive correlation with uromodulin, likely linked to the extracellular volume status. The presence of glycosuria and the use of uricosuric drugs, which both increased the fraction excretion of urate, were independently associated with a lower uromodulin excretion, suggesting novel interactions between uric acid and uromodulin excretion. CONCLUSIONS: In this large cohort, the excretion of uromodulin correlates with clinical, genetic, and urinary factors. The strongest associations were between uric acid, sodium, and uromodulin excretions and are likely linked to the extracellular volume status. PMID- 26683888 TI - Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population. AB - BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age+/-SD, 45+/-17 years) who underwent renal ultrasonography and performed a 24 hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53+/-11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population. PMID- 26683889 TI - Tamm Horsfall Glycoprotein and Uromodulin: It Is All about the Tubules! PMID- 26683891 TI - Temporal Trends in AKI: Insights from Big Data. PMID- 26683890 TI - Exploring Potential Reasons for the Temporal Trend in Dialysis-Requiring AKI in the United States. AB - BACKGROUND AND OBJECTIVES: The population incidence of dialysis-requiring AKI has risen substantially in the last decade in the United States, and factors associated with this temporal trend are not well known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study using data from the Nationwide Inpatient Sample, a United States nationally representative database of hospitalizations from 2007 to 2009. We used validated International Classification of Diseases, Ninth Revision codes to identify hospitalizations with dialysis-requiring AKI and then, selected the diagnostic and procedure codes most highly associated with dialysis-requiring AKI in 2009. We applied multivariable logistic regression adjusting for demographics and used a backward selection technique to identify a set of diagnoses or a set of procedures that may be a driver for this changing risk in dialysis-requiring AKI. RESULTS: From 2007 to 2009, the population incidence of dialysis-requiring AKI increased by 11% per year (95% confidence interval, 1.07 to 1.16; P<0.001). Using backward selection, we found that the temporal trend in the six diagnoses, septicemia, hypertension, respiratory failure, coagulation/hemorrhagic disorders, shock, and liver disease, sufficiently and fully accounted for the temporal trend in dialysis-requiring AKI. In contrast, temporal trends in 15 procedures most commonly associated with dialysis-requiring AKI did not account for the increasing dialysis-requiring AKI trend. CONCLUSIONS: The increasing risk of dialysis-requiring AKI among hospitalized patients in the United States was highly associated with the changing burden of six acute and chronic conditions but not with surgeries and procedures. PMID- 26683892 TI - Advances in primate stable isotope ecology-Achievements and future prospects. AB - Stable isotope biogeochemistry has been used to investigate foraging ecology in non-human primates for nearly 30 years. Whereas early studies focused on diet, more recently, isotopic analysis has been used to address a diversity of ecological questions ranging from niche partitioning to nutritional status to variability in life history traits. With this increasing array of applications, stable isotope analysis stands to make major contributions to our understanding of primate behavior and biology. Most notably, isotopic data provide novel insights into primate feeding behaviors that may not otherwise be detectable. This special issue brings together some of the recent advances in this relatively new field. In this introduction to the special issue, we review the state of isotopic applications in primatology and its origins and describe some developing methodological issues, including techniques for analyzing different tissue types, statistical approaches, and isotopic baselines. We then discuss the future directions we envision for the field of primate isotope ecology. Am. J. Primatol. 78:995-1003, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26683893 TI - Free-style free flap: Anterior thigh flap: Report of a case of subtotal glossectomy reconstruction. PMID- 26683894 TI - Successful treatment of refractory seizures with phenobarbital, propofol, and medetomidine following congenital portosystemic shunt ligation in a dog. AB - OBJECTIVE: To report a case of refractory seizures following congenital portosystemic shunt (CPSS) ligation that regained normal neurologic and hepatic function with novel treatment. Medical care included constant rate infusions (CRI) of propofol and medetomidine in conjunction with phenobarbital and supportive intensive care. CASE SUMMARY: A 2-year-old neutered male Bichon Frise was diagnosed with a single extrahepatic CPSS based on typical clinical signs, laboratory data, abdominal ultrasound, and computed tomographic angiography. Following initiation of standard medical treatment, a complete surgical ligation of the CPSS was performed. Recovery was uneventful until postligation neurologic dysfunction developed 54 hours after surgery. Seizures were controlled with phenobarbital (6 mg/kg IM q 12 h) and propofol CRI (0.3-0.6 mg/kg/min). Attempts to wean the dog from the propofol CRI resulted in recurrence of seizure activity until the addition of medetomidine CRI (0.016 MUg/kg/min) 76 hours after initiation of drug-induced coma allowed gradual discontinuation of the propofol CRI. The dog regained full neurologic and hepatic function and had no further seizure activity apart from a small number of seizure episodes 5 and 22 months later. Adjustments in antiepileptic treatment resulted in no further neurologic dysfunction at 27-month follow-up. NEW OR UNIQUE INFORMATION PROVIDED: This report highlights the potential benefit of medetomidine CRI for treatment of postattenuation refractory seizures, which to date have proven impossible to predict and difficult to treat with high mortality rates and persistent neurological deficits in surviving animals. Neuroprotective, drug-sparing, and anti-hypertensive features of medetomidine might improve outcome in postligation refractory seizures. Further investigation and clinical application of medetomidine CRI may improve outcome in this complication of CPSS attenuation. PMID- 26683895 TI - Low-Temperature in Situ Growth of Graphene on Metallic Substrates and Its Application in Anticorrosion. AB - Metal or alloy corrosion brings about huge economic cost annually, which is becoming one area of growing concern in various industries, being in bulk state or nanoscale range. Here, single layer or few layers of graphene are deposited on various metallic substrates directly at a low temperature down to 400 degrees C. These substrates can be varied from hundreds-micrometer bulk metallic or alloy foils to tens of nanometer nanofibers (NFs). Corrosion analysis reveals that both graphene-grown steel sheets and NFs have reduced the corrosion rate of up to ten times lower than that of their bare corresponding counterparts. Moreover, such low-temperature in situ growth of graphene demonstrates stable and long-lasting anticorrosion after long-term immersion. This new class of graphene coated nanomaterials shows high potentials in anticorrosion applications for submarines, oil tankers/pipelines, and ruggedized electronics. PMID- 26683896 TI - Post-surgical functional recovery, lumbar lordosis, and range of motion associated with MR-detectable redundant nerve roots in lumbar spinal stenosis. AB - OBJECTIVE: T1- and T2-weighted magnetic resonance images (MRI) can reveal lumbar redundant nerve roots (RNRs), a result of chronic compression and nerve elongation associated with pathogenesis of cauda equina claudication (CEC) in degenerative lumbar canal stenosis (DLCS). The study investigated effects of lumbar lordosis angle and range of motion on functional recovery in lumbar stenosis patents with and without RNRs. METHODS: A retrospective study was conducted of 93 lumbar spinal stenosis patients who underwent decompressive surgery. Eligible records were assessed by 3 independent blinded radiologists for presence or absence of RNRs on sagittal T2-weighted MR (RNR and non-RNR groups), pre- and post-operative JOA score, lumbar lordosis angle, and range of motion. RESULTS: Of 93 total patients, the RNR group (n=37, 21/37 female) and non-RNR group (n=56; 31/56 female) had similar preoperative conditions (JOA score) and were not significantly different in age (mean 64.19 +/- 8.25 vs. 62.8 +/- 9.41 years), symptom duration (30.92 +/- 22.43 vs. 28.64 +/- 17.40 months), or follow up periods (17.35 +/- 4.02 vs. 17.75 +/- 4.29 mo) (all p>0.4). The non-RNR group exhibited significantly better final JOA score (p=0.015) and recovery rate (p=0.002). RNR group patients exhibited larger lumbar lordosis angles in the neutral position (p=0.009) and extension (p=0.021) and larger range of motion (p=0.008). CONCLUSIONS: Poorer surgical outcomes in patients with RNRs indicated that elevated lumbar lordosis angle and range of motion increased risks of RNR formation, which in turn may cause poorer post-surgical recovery, this information is possibly useful in prognostic assessment of lumbar stenosis complicated by RNRs. PMID- 26683897 TI - Demographic and Clinical Features of Chinese Heroin Users Who Switch from Non injection to Injection. AB - BACKGROUND: Injection drug users (IDUs) are at high-risk for acquiring human immunodeficiency virus, hepatitis C virus, and other infections, and delaying the switch from non-injection drug use to injection to drug use could reduce the spread of these infections. OBJECTIVES: To estimate the incidence of switching from non-injected heroin use (usually smoking or "chasing") to injection and to investigate the risk factors for this change. METHODS: We reviewed the socio demographic and clinical data of 7305 heroin-dependent patients treated at a detoxification clinic of a university-affiliated psychiatric hospital in China from January 2000 to February 2009. RESULTS: Within 1 year, the majority of non injection drug users (NIDUs) transitioned to IDUs (59.4% within 6 months and 76.7% within 12 months). Multiple logistic regression analysis showed that marital status, years of education, employment status, age at onset of heroin use, duration of drug abuse, and initial dose were associated with the switch from NIDU to IDU. Being married (B = -0.410, OR = 0.664), being employed (B = 0.243, OR = 0.784), and older age at onset (B = -0.040, OR = 0.961) were protective factors. More education (B = 0.120, OR = 1.128), longer duration of drug abuse (B = 0.010, OR = 1.010), and a higher dose at initial drug use (B = 0.234, OR = 1.264) were risk factors. CONCLUSIONS/IMPORTANCE: The study has identified several risk factors for the switch to injection among heroin users. Understanding these factors can help design new approaches to more specifically target high-risk populations and high-risk behaviors to delay or prevent the transition to injection. PMID- 26683899 TI - An integrated mathematical model of the human cardiopulmonary system: model development. AB - Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. PMID- 26683900 TI - Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology. AB - Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 +/- 7.8 vs. 13.8 +/- 7.1 * 10(4) W.m(-2).s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 +/- 32.8 vs. -59.4 +/- 34.2 * 10(2) W.m(-2).s( 1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 +/- 29.5 * 10(4) W.m(-2).s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 +/- 12.6 * 10(3) W.m(-2).s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA. PMID- 26683901 TI - Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts. AB - Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg.kg(-1).day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cepsilon expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. PMID- 26683903 TI - Pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting. AB - Fibroblast growth factor 21 (FGF21) functions as an endocrine hormone to regulate energy metabolism. Circulating FGF21 is derived from the liver and is produced in response to alterations of nutritional status. Here we show the effects of liraglutide, a human glucagon-like-peptide-1 (GLP-1) receptor agonist, injected into the third cerebral ventricle on body weight and plasma FGF21 levels in free feeding mice, food-deprived mice, and mice provided 1g after the injection. In free-feeding mice, liraglutide (5-100MUg/kg) injected into the third cerebral ventricle suppressed food intake and body weight after 24h in a dose-dependent manner. Liraglutide (50 and 100MUg/kg) significantly increased plasma FGF21 levels and hepatic FGF21 expression, whereas smaller doses (5 and 10MUg/kg) had no effect. In food-deprived mice, body weight did not differ significantly between the saline control and liraglutide-treated groups, but liraglutide (100MUg/kg) significantly decreased plasma FGF21 levels at 24h compared with the saline control. In mice provided 1g food, body weight did not differ significantly between the saline control and liraglutide-treated groups, but liraglutide (50MUg/kg) significantly decreased plasma FGF21 levels at 24h compared with the saline control. These findings suggest that intracerebral injection of liraglutide decreases body weight by inhibiting food intake and increases plasma FGF21 levels in free-feeding mice, whereas it suppresses the elevations of plasma FGF21 levels induced by fasting or the restricted feeding. Thus, pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting. PMID- 26683902 TI - Stem cell-based therapies to promote angiogenesis in ischemic cardiovascular disease. AB - Stem cell therapy is a promising approach for the treatment of tissue ischemia associated with myocardial infarction and peripheral arterial disease. Stem and progenitor cells derived from bone marrow or from pluripotent stem cells have shown therapeutic benefit in boosting angiogenesis as well as restoring tissue function. Notably, adult stem and progenitor cells including mononuclear cells, endothelial progenitor cells, and mesenchymal stem cells have progressed into clinical trials and have shown positive benefits. In this review, we overview the major classes of stem and progenitor cells, including pluripotent stem cells, and summarize the state of the art in applying these cell types for treating myocardial infarction and peripheral arterial disease. PMID- 26683904 TI - 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A, two diterpenes isolated from Euphorbia helioscopia suppress microglia activation. AB - Microglia activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors. In the present study, we found that two diterpenes isolated from Euphorbia helioscopia, 15-O-Acetyl-3-O benzoylcharaciol and helioscopinolide A suppressed NO and PGE2 production by inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. The diterpenes also inhibited the production of ROS and proinflammatory cytokines including interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha, the mechanism involved the NF-kappaB but not Akt and mitogen-activated protein kinase (MAPK) pathway. Moreover, the two diterpenes also attenuate microglia activation mediated neuronal death. These results suggest that 15-O-Acetyl-3-O benzoylcharaciol and helioscopinolide A may provide potential therapeutic strategy for various neuroinflammatory diseases. PMID- 26683905 TI - Serotonergic projections from the raphe nuclei to the subthalamic nucleus; a retrograde- and anterograde neuronal tracing study. AB - The objective of this study is to establish which subdivision of the dorsal raphe nucleus (DRN) supplies serotonergic projections to the subthalamic nucleus (STN) in the rat brain. Several studies in recent years have shown that serotonin (5 HT) might have a therapeutic role in the most prevalent basal ganglia (BG) movement disorder, Parkinson's disease (PD), but, because of the depletion of dopaminergic input to the BG, l-DOPA has been the main treatment for PD patients. Autoradiography showed that serotonin receptors 5-HT1B and 5-HT2C and the serotonin transporter were present in STN, whereas the 5-HT1A and 5-HT2A not were present. Retrograde tracer FluoroGold or Choleratoxin subunit B were iontophoretically delivered in the STN and combined with immunohistochemistry for 5-HT in order to map the topographic organization in the dorsal raphe system. The study showed that approximately 320+/-137 neurons were retrogradely traced from each STN to the DRN, located mainly in the dorsal- and ventrolateral DRN, and of these 108+/-42 or 34% co-localized 5-HT. Additionally anterograde tracer PHA-L was injected in the DRN to confirm projections to STN and accordingly only a sparse number of axon terminals were observed in the STN. PMID- 26683906 TI - The planar cell polarity protein Vangl2 is involved in postsynaptic compartmentalization. AB - The excitatory postsynaptic region of the vertebrate hippocampus is usually compartmentalized into the postsynaptic density (PSD) and N-cadherin-rich domain, which is important for synaptic adhesion. However, the molecular mechanisms underlying the compartment formation are unknown. In the present report, we show that the planar cell polarity (PCP) protein Van Gogh-like 2 (Vangl2) plays a role in this regionalization. In cultured rat hippocampal neurons that were subjected to Vangl2 expression silencing, the formed clusters of PSD-95, one of the major scaffolding proteins in PSD, tended to overlap with those of N-cadherin. Further, in the dendrites of these neurons, the immunofluorescence of PSD-95 was to some extent diffused, without a significant change in the total signal. Because Vangl2 physically interacts with both PSD-95 and N-cadherin in vivo, these results suggest that a PCP-related direct molecular mechanism underlies the horizontal polarization of the postsynaptic regions. PMID- 26683907 TI - Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study. AB - Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID- 26683908 TI - Vitamin D Status and the Risk of Anemia in Community-Dwelling Adults: Results from the National Health and Nutrition Examination Survey 2001-2006. AB - Low vitamin D status has been implicated in several chronic medical conditions and unfavorable health outcomes. Our goal was to investigate whether serum 25 hydroxyvitamin D (25OHD) levels are a potentially modifiable risk factor for anemia in a nationally representative cohort of community-dwelling individuals in the United States. We performed a cross-sectional study of 5456 individuals (>=17 years) from the National Health and Nutrition Examination Survey from 2001 to 2006. Locally weighted scatterplot smoothing (LOWESS) was used to graphically depict the relationship between serum 25OHD levels and the cumulative frequency of anemia. Multivariable logistic regression models were then used to assess the independent association of 25OHD levels with anemia, while controlling for age, sex, race, body mass index, chronic kidney disease, as well as serum levels of C reactive protein, ferritin, iron, vitamin B12, and folic acid. The mean (standard error) 25OHD and hemoglobin levels in the analytic group were 23.5 (0.4) ng/mL and 14.4 (0.1) g/dL, respectively. Prevalence of anemia was 3.9%. Locally weighted scatterplot smoothing analysis demonstrated a near-linear relationship between vitamin D status and cumulative frequency of anemia up to 25OHD levels of approximately 20 ng/mL. With increasing 25OHD levels, the curve flattened out progressively. Multivariable regression analysis demonstrated an inverse association of 25OHD levels with the risk of anemia (adjusted odds ratio 0.97; 95% confidence interval 0.95-0.99 per 1 ng/mL change in 25OHD). Compared to individuals with >=20 ng/mL, individuals with 25OHD levels <20 ng/mL were more likely to be anemic (adjusted odds ratio 1.64; 95% confidence interval 1.08 2.49). In a nationally representative sample of community-dwelling individuals in the United States, low 25OHD levels were associated with increased risk of anemia. Randomized controlled trials are needed to determine whether optimizing vitamin D status can reduce the burden of anemia in the general population. PMID- 26683909 TI - Plasma Epstein-Barr Viral Deoxyribonucleic Acid Predicts Worse Outcomes in Pediatric Nonmetastatic Nasopharyngeal Carcinoma Patients: An Observational Study of 89 Cases in an Endemic Area. AB - To evaluate the clinical significance of pretreatment levels of plasma Epstein Barr virus DNA (pEBV DNA) on prognoses in pediatric nasopharyngeal carcinoma (NPC) patients. Eighty-nine patients aged 21 years old or younger with nonmetastatic NPC were evaluated to determine the effect of pEBV DNA levels on progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS). Survival probabilities in patient groups that were segregated by clinical stage or pEBV DNA load (low or high) were compared. The median pretreatment concentrations of pEBV DNA were 3440 copies/mL in 35 patients with stage III disease and 14,900 copies/mL in 50 patients with stage IV disease (P = 0.059). The median concentration of pEBV DNA was 34,500 copies/mL in 17 patients with relapse, which was higher than the concentration in 72 patients without relapse, who had a median level of 4985 copies/mL (P = 0.057). Further study showed that pretreatment pEBV DNA load was an independent prognostic indicator in pediatric NPC patients. High pEBV DNA was associated with adverse clinical outcomes, including PFS [3-year PFS rate = 80.5% versus 95.8%, hazard ratio (HR) = 5.00, 95% confidence interval (CI) = 1.00-25.00; P = 0.050], DMFS (3 year DMFS rate = 80.5% versus 95.8%, HR = 5.20, 95% CI = 1.04-26.00; P = 0.045), and OS (3-year OS rate = 82.9% versus 95.8%, HR = 5.41, 95% CI = 1.08-27.22; P = 0.040). Pretreatment pEBV DNA load was an independent prognostic indicator for PFS, DMFS, and OS in pediatric patients with NPC. Prospective studies, however, are needed to validate these results. PMID- 26683911 TI - Case Report of Percutaneous Retrograde Transcollateral Recanalization of the Superior Mesenteric Artery via the Celiac Artery for Acute Mesenteric Ischemia. AB - Revascularization for acute mesenteric ischemia (AMI) can be achieved through a bypass from the aorta or iliac arteries, embolectomy, open exposure of SMA and retrograde recanalization and stent, or percutaneous antegrade stenting. Flush occlusion of the SMA can make antegrade recanalization very challenging and is usually unsuccessful. We present a novel approach for recanalization of superior mesenteric artery (SMA) via the celiac artery for acute mesenteric ischemia. A 69 year-old lady with previous endarterectomy of SMA and extensive small bowel resection presented with severe abdominal pain, emesis, leukocytosis, and imaging finding of new SMA flush occlusion. She refused to consent for a laparotomy. Percutaneous retrograde transcollateral recanalization of SMA was performed via the celiac artery through the pancreaticoduodenal arcade, and the SMA then stented. This resulted in subsequent resolution of patient's symptoms and discharge. SMA revascularization with retrograde transcollateral wiring technique is an important tool in the armamentarium of the vascular care specialist when antegrade percutaneous approach and open exposure via laparotomy are not an option. PMID- 26683912 TI - Comparison on Response and Dissolution Rates Between Ursodeoxycholic Acid Alone or in Combination With Chenodeoxycholic Acid for Gallstone Dissolution According to Stone Density on CT Scan: Strobe Compliant Observation Study. AB - Medical dissolution of gallstone is usually performed on radiolucent gallstones in a functioning gallbladder. However, absence of visible gallstone on plain abdominal x-ray does not always preclude calcification. This study aims to compare the response and dissolution rates between ursodeoxycholic acid (UDCA) alone or in combination with chenodeoxycholic acid (CDCA) according to stone density on computed tomography (CT) scan. A total of 126 patients underwent dissolution therapy with either UDCA alone or combination of CDCA and UDCA (CNU) from December 2010 to March 2014 at Korea University Ansan Hospital. In the end, 81 patients (CNU group = 44, UDCA group = 37) completed dissolution therapy for 6 months. Dissolution rate (percentage reduction in the gallstone volume) and response to therapy (complete dissolution or partial dissolution defined as reduction in stone volume of >50%) were compared between the 2 groups. Dissolution and response rates of sludge was also compared between the 2 groups. The overall response rate was 50.6% (CNU group 43.2% vs UDCA group 59.5%, P = 0.14), and the overall dissolution rate was 48.34% (CNU group 41.5% vs UDCA group 56.5%, P = 0.13). When analyzed according to stone density, response rate was 33.3%, 87.1%, 30.0%, and 6.2% for hypodense, isodense, hyperdense, and calcified stones, respectively. Response rate (85.7% vs 88.2%, P = 0.83) and dissolution rate (81.01% vs 85.38%, P = 0.17) of isodense stones were similar between CNU and UDCA group. When only sludge was considered, the overall response rate was 87.5% (CNU group 71.4% vs UDCA group 94.1%, P = 0.19), and the overall dissolution rate was 85.42% (CNU group 67.9% vs UDCA group 92.7%, P = 0.23). Patients with isodense gallstones and sludge showed much better response to dissolution therapy with CNU and UDCA showing comparable efficacy. Therefore, CT scan should be performed before medication therapy if stone dissolution is intended. PMID- 26683910 TI - Prevalence of Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. AB - We aimed to obtain overall and regional estimates of hypertension prevalence, and to examine the pattern of this disease condition across different socio demographic characteristics in low-and middle-income countries. We searched electronic databases from inception to August 2015. We included population-based studies that reported hypertension prevalence using the current definition of blood pressure >=140/90 mm Hg or self-reported use of antihypertensive medication. We used random-effects meta-analyses to pool prevalence estimates of hypertension, overall, by World Bank region and country income group. Meta regression analyses were performed to explore sources of heterogeneity across the included studies. A total of 242 studies, comprising data on 1,494,609 adults from 45 countries, met our inclusion criteria. The overall prevalence of hypertension was 32.3% (95% confidence interval [CI] 29.4-35.3), with the Latin America and Caribbean region reporting the highest estimates (39.1%, 95% CI 33.1 45.2). Pooled prevalence estimate was also highest across upper middle income countries (37.8%, 95% CI 35.0-40.6) and lowest across low-income countries (23.1%, 95% CI 20.1-26.2). Prevalence estimates were significantly higher in the elderly (>=65 years) compared with younger adults (<65 years) overall and across the geographical regions; however, there was no significant sex-difference in hypertension prevalence (31.9% vs 30.8%, P = 0.6). Persons without formal education (49.0% vs 24.9%, P < 0.00001), overweight/obese (46.4% vs 26.3%, P < 0.00001), and urban settlers (32.7% vs 25.2%, P = 0.0005) were also more likely to be hypertensive, compared with those who were educated, normal weight, and rural settlers respectively. This study provides contemporary and up-to-date estimates that reflect the significant burden of hypertension in low- and middle income countries, as well as evidence that hypertension remains a major public health issue across the various socio-demographic subgroups. On average, about 1 in 3 adults in the developing world is hypertensive. The findings of this study will be useful for the design of hypertension screening and treatment programmes in low- and middle-income countries. PMID- 26683913 TI - A Review of GM-CSF Therapy in Sepsis. AB - Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID- 26683914 TI - Indications to Hospital Admission and Isolation of Children With Possible or Defined Tuberculosis: Systematic Review and Proposed Recommendations for Pediatric Patients Living in Developed Countries. [Corrected]. AB - Tuberculosis (TB) is a re-emerging health problem in developed countries. This paper is part of large guidelines on the global management of TB in children, by a group of scientific societies. It describes the indications to hospitalization of children with suspected or diagnosed TB, the isolation measures, hospital discharge, and re-admission into the community. Using the Consensus Conference method, relevant publications in English were identified by means of a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Available data on indications to hospitalization were mainly indirect and largely derived from observational studies. They include: (1) host-related risk factors, the main being age <12 months, immune deficiencies, and malnutrition; (2) TB-related clinical conditions that resemble those of pneumonia but also include drug-resistance; and (3) social and logistic conditions. The latter are based on opinion and depend on local conditions. Analysis of the literature showed that patients hospitalized with suspected pulmonary TB should be put in precautionary respiratory isolation regardless of their age while they await diagnosis. The general conditions for re admission into the community are at least 14 days of effective treatment and negative microscopic tests of 3 consecutive samples in previously microscopically positive patients. This is the first paper that provides indications to hospitalization of children with TB. Most recommendations are generally applicable in all developed countries. Some might need an adaptation to local setting, epidemiological, parameters, and availability of specific health-care facilities. PMID- 26683915 TI - Validation of T Stage According to Depth of Invasion and N Stage Subclassification Based on Number of Metastatic Lymph Nodes for Distal Extrahepatic Bile Duct (EBD) Carcinoma. AB - According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: >= 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1-3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs >= 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more accurate evaluation of N stage in distal EBD carcinoma. We propose an alternative T classification using DoI and 3-tier sub-classification of N stage for distal EBD carcinoma. PMID- 26683916 TI - Prevalence of Depression Among College-Goers in Mainland China: A Methodical Evaluation and Meta-Analysis. AB - There are no proper statistics available to assess how much of a burden it is to them. This study was conducted to gauge the pooled prevalence and offer evidence in support of few prevention and regulation strategies. A methodical literature search was conducted with the help of the Web of Knowledge, PubMed, Chinese Web of Knowledge, Wanfang, and Chongqing VIP databases. Furthermore, articles published from 2000 to 2014, reporting about the estimated prevalence of depression among college students in mainland China, were covered as well. In this study, a meta-analysis was deployed to approximate the overall prevalence of depression among college-goers in mainland China. A total of 45 studies were conducted on 50,826 participants. The average pooled prevalence of depression was 30.39% (26.38-34.55%). Subgroup analyses showed that 29.45% (22.88-36.48%) were men and 28.65% (23.44-34.16%) were women. Furthermore, 28.10% (22.83-33.70%) were from the northern part and 32.44% (26.67-38.48%) were from the southern. The prevalence of depression was 30.45% (23.96-37.36%) for sample sizes of <500 subjects, 30.99% (25.08-37.23%) for samples with 500 to 1000 people, and 29.54% (33.32-37.33%) in case of samples with >1000 people. Publications between 2000 and 2006 showed a depression prevalence of 8.45% (22.34-35.00%), whereas 30.52% (21.30-40.61%) and 31.79% (27.31-36.45%) were the corresponding values according to publications during 2007 to 2011 and 2012 to 2014. The prevalence of depression among college students in mainland China had reached the world's epidemic level. PMID- 26683918 TI - Esophageal Involvement of Immunoglobulin G4-Related Disease: A Case Report and Literature Review. AB - Immunoglobulin G4 (IgG4)-related disease is characterized by the typical histopathological features of a dense lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells, a high ratio of IgG4- to IgG-positive cells, storiform fibrosis (cellular fibrosis organized in an irregular whorled pattern), obliterative phlebitis, and variable presence of eosinophils. The disease exhibits systemic involvement but very rarely involves the esophagus. A 33-year old man was admitted to our hospital for evaluation of a 1-year history of progressive dysphagia. Neck imaging revealed a 3.9-cm mass in the cervical esophagus and multifocal calcified lymph nodes in the lower neck and mediastinum. Two previous tertiary hospitals failed to diagnose the patient's condition despite the use of ultrasound-guided needle biopsy of the neck tumor. We performed neck imaging studies, a flexible endoscopic swallowing study, high resolution manometry, upper endoscopy, and a review of the previous pathologic slides. The patient was finally diagnosed with IgG4-related esophagitis and showed a good response to corticosteroid therapy. We herein report a rare case of dysphagia associated with IgG4-related disease and present a review of the literature. PMID- 26683919 TI - Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer: A Systematic Review and Meta-Analysis. AB - Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer. By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated. Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76 (95% CI = 0.70-0.82) and 0.84 (95% CI = 0.78-0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99-3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21-4.77, P = 0.012). The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians. PMID- 26683917 TI - Osteoarticular Infections Caused by Non-Aspergillus Filamentous Fungi in Adult and Pediatric Patients: A Systematic Review. AB - Osteoarticular mycoses due to non-Aspergillus moulds are uncommon and challenging infections. A systematic literature review of non-Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013. Among 145 patients were 111 adults (median age 48.5 [16-92 y]) and 34 pediatric patients (median age 7.5 [3-15 y]); 114 (79.7%) were male and 88 (61.9%) were immunocompromised. Osteomyelitis was due to direct inoculation in 54.5%. Trauma and puncture wounds were more frequent in children (73.5% vs 43.5%; P = 0.001). Prior surgery was more frequent in adults (27.7% vs 5.9%; P = 0.025). Vertebral (23.2%) and craniofacial osteomyelitis (13.1%) with neurological deficits predominated in adults. Lower limb osteomyelitis (47.7%) and knee arthritis (67.8%) were predominantly seen in children. Hyalohyphomycosis represented 64.8% of documented infections with Scedosporium apiospermum (33.1%) and Lomentospora prolificans (15.8%) as the most common causes. Combined antifungal therapy and surgery was used in 69% of cases with overall response in 85.8%. Median duration of therapy was 115 days (range 5-730). When voriconazole was used as single agent for treatment of hyalohyphomycosis and phaeohyphomycosis, an overall response rate was achieved in 94.1% of cases. Non-Aspergillus osteoarticular mycoses occur most frequently in children after injury and in adults after surgery. Accurate early diagnosis and long-course therapy (median 6 mo) with a combined medical surgical approach may result in favorable outcome. PMID- 26683920 TI - Comparison of Direct Anterior and Lateral Approaches in Total Hip Arthroplasty: A Systematic Review and Meta-Analysis (PRISMA). AB - The direct anterior approach (DAA) to total hip arthroplasty has been promoted as a minimally invasive alternative to the lateral approach, which we sought to verify by systematically reviewing and meta-analyzing the literature comparing clinical, radiographic, and surgical outcomes. Two reviewers independently searched PubMed, OVID, and Web of Science databases for randomized controlled trials (RCTs) and cohort studies comparing the DAA and lateral approach for total hip arthroplasty. Quality of RCTs was assessed using the Jadad scoring system, quality of cohort studies, using the Minors system. Data were extracted and meta analyzed or qualitatively synthesized for primary outcomes (function, complications, and hospitalization time) and several secondary outcomes. Data were extracted from 12 trials involving 4901 arthroplasty procedures. Meta analysis showed that DAA was associated with significantly shorter hospitalization than the lateral approach, as well as greater functional rehabilitation and lower perceived pain during the early postoperative period. On the other hand, DAA was associated with longer surgery time. The 2 approaches were associated with similar rates of perioperative surgical complications and transfusions, as well as similar radiographic analysis results. Although DAA may provide shorter hospitalization and faster recovery during the early postoperative period, the available evidence is still insufficient to conclude whether the DAA or lateral approach is superior for total hip arthroplasty. More high-quality studies and subsequent meta-analyses are needed. PMID- 26683921 TI - Liver Fibrosis in HIV Patients Receiving a Modern cART: Which Factors Play a Role? AB - Liver-related death in human immunodeficiency virus (HIV)-infected individuals is about 10 times higher compared with the general population, and the prevalence of significant liver fibrosis in those with HIV approaches 15%. The present study aimed to assess risk factors for development of hepatic fibrosis in HIV patients receiving a modern combination anti-retroviral therapy (cART). This cross sectional prospective study included 432 HIV patients, of which 68 (16%) patients were anti-hepatitis C virus (HCV) positive and 23 (5%) were HBsAg positive. Health trajectory including clinical characteristics and liver fibrosis stage assessed by transient elastography were collected at inclusion. Liver stiffness values >7.1 kPa were considered as significant fibrosis, while values >12.5 kPa were defined as severe fibrosis. Logistic regression and Cox regression uni- and multivariate analyses were performed to identify independent factors associated with liver fibrosis. Significant liver fibrosis was detected in 10% of HIV mono infected, in 37% of HCV co-infected patients, and in 18% of hepatitis B virus co infected patients. The presence of diabetes mellitus (odds ratio [OR] = 4.6) and FIB4 score (OR = 2.4) were independently associated with presence of significant fibrosis in the whole cohort. Similarly, diabetes mellitus (OR = 5.4), adiposity (OR = 4.6), and the FIB4 score (OR = 3.3) were independently associated with significant fibrosis in HIV mono-infected patients. Importantly, cumulative cART duration protected, whereas persistent HIV viral replication promoted the development of significant liver fibrosis along the duration of HIV infection. Our findings strongly indicate that besides known risk factors like metabolic disorders, HIV may also have a direct effect on fibrogenesis. Successful cART leading to complete suppression of HIV replication might protect from development of liver fibrosis. PMID- 26683923 TI - Bacterial Infection in Deep Paraspinal Muscles in a Parturient Following Epidural Analgesia: A Case Report and Literature Review: A CARE-Compliant Article. AB - Bacterial infection related to epidural catheterizations could occur. In general, the incidence of postoperative infection at the insertion site is very low. Paucity literatures are reported for paraspinal muscle infection after epidural analgesia in parturient. We report a case of paraspinal muscle infection shortly after epidural analgesia in a parturient, who was subjected to because of threatened preterm labor. Epidural morphine was administered for 2 days for childbirth pain control. She began to have constant low-back pain and fever on postpartum Day 2. Magnetic resonance image revealed a broad area of subcutaneous edema with a continuum along the catheter trajectory deep to the paraspinal muscles. A catheter-related bacterial infection was suspected. The surgical debridement and drainage was required combined with intravenous antibiotics on postpartum Day 3. She was soon cured uncomplicatedly. Epidural analgesia is effective to control labor pain and, in general, it is safe. However, the sequelae of complicated infection may be underestimated. A literature search yielded 7 other cases of catheter-related epidural abscess or soft tissue infection. Vigilance for these infections, especially in postpartum patients with backache, is needed. Moreover, early detection and proper treatment of infectious signs at postanesthetic visit are very important. PMID- 26683922 TI - A Survey of Pediatric CT Protocols and Radiation Doses in South Korean Hospitals to Optimize the Radiation Dose for Pediatric CT Scanning. AB - Children are at greater risk of radiation exposure than adults because the rapidly dividing cells of children tend to be more radiosensitive and they have a longer expected life time in which to develop potential radiation injury. Some studies have surveyed computed tomography (CT) radiation doses and several studies have established diagnostic reference levels according to patient age or body size; however, no survey of CT radiation doses with a large number of patients has yet been carried out in South Korea. The aim of the present study was to investigate the radiation dose in pediatric CT examinations performed throughout South Korea. From 512 CT (222 brain CT, 105 chest CT, and 185 abdominopelvic CT) scans that were referred to our tertiary hospital, a dose report sheet was available for retrospective analysis of CT scan protocols and dose, including the volumetric CT dose index (CTDIvol), dose-length product (DLP), effective dose, and size-specific dose estimates (SSDE). At 55.2%, multiphase CT was the most frequently performed protocol for abdominopelvic CT. Tube current modulation was applied most often in abdominopelvic CT and chest CT, accounting for 70.1% and 62.7%, respectively. Regarding the CT dose, the interquartile ranges of the CTDIvol were 11.1 to 22.5 (newborns), 16.6 to 39.1 (<=1 year), 14.6 to 41.7 (2-5 years), 23.5 to 44.1 (6-10 years), and 31.4 to 55.3 (<=15 years) for brain CT; 1.3 to 5.7 (<=1 year), 3.9 to 6.8 (2-5 years), 3.9 to 9.3 (6-10 years), and 7.7 to 13.8 (<=15 years) for chest CT; and 4.0 to 7.5 (<=1 year), 4.2 to 8.9 (2-5 years), 5.7 to 12.4 (6-10 years), and 7.6 to 16.6 (<=15 years) for abdominopelvic CT. The SSDE and CTDIvol were well correlated for patients <5 years old, whereas the CTDIvol was lower in patients >=6 years old. Our study describes the various parameters and dosimetry metrics of pediatric CT in South Korea. The CTDIvol, DLP, and effective dose were generally lower than in German and UK surveys, except in certain age groups. PMID- 26683924 TI - Intrathoracic Involvements of Immunoglobulin G4-Related Sclerosing Disease. AB - To investigate clinical and radiological features of IgG4-related disease (IgG4 RD) patients with intrathoracic involvement. A prospective cohort study was performed and IgG4-RD patients were enrolled from January 2011 to March 2015 in Peking Union Medical College Hospital, in which the clinical and radiological characteristics of IgG4-RD patients with intrathoracic involvement were summarized. Out of total 248 cases with IgG4-RD, 87 cases had intrathoracic lesions, including 58 male cases and 29 female cases, with average age of 54.19 +/- 13.80 years. Hilar and mediastinal lymphadenopathy were the most common manifestations of IgG4-related intrathoracic disease, accounting for 52.9% (46/87). Other imaging findings of pulmonary disease included: solid nodular (25.3%), round-shaped ground-glass opacities (9.2%), alveolar-interstitial type (20.7%), bronchovascular type (23.0%), pleural effusion (4.6%), and pleural nodules or thickening (16.1%). Only 27 patients presented with respiratory symptoms, including cough, breathless, chest pain, and asthma. Compared with patients without intrathoracic disease, IgG4-related intrathoracic disease had higher IgG4 and C-reactive protein level, and higher incidence of allergy, fever, and multi-organ involvement. Most of lung interstitial disease, mediastinal mass, and bronchial thickening were sensitive to corticosteroid and immunosuppressant therapy, while 36.3% (8/22) of solitary nodular lesions were unresponsive to treatment. Eight patients were on no treatment, with 5 cases remained stable, 2 patients improved spontaneously, and 1 patient was lost follow-up. Intrathoracic lesions are not rare in patients with IgG4-RD, involving bronchial thickening, nodules, ground glass opacity, pleural thickening/effusion, lymphadenopathy, etc. Efficacy of corticosteroid and immunosuppressant therapy were noted in most of patients with lung interstitial disease, mediastinal mass, and bronchial thickening. PMID- 26683925 TI - A Systematic Review and Meta-Analysis of the Clinical Appropriateness of Blood Transfusion in China. AB - The issue of the clinical appropriateness of blood transfusion has become a focus of transfusion medicine worldwide. In China, irrational uses of blood have often been reported in recent years. However, to date there lacks a systematic review of the rational uses of blood. This study aimed to determine the clinical appropriateness of blood transfusion in China. We searched PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and Chinese BioMedical Literature Database, and the retrieval cut-off date was June 31, 2015. SPSS 17.0 and MetaAnalyst 3.13 were employed as the statistics tools in this review. A pooled rate of clinical inappropriateness of transfusion was analyzed by DerSimonian-Laird method. In this study, a total of 39 observational studies were included, which related to 75,132 cases of blood transfusion. According to the meta-analysis results, the overall incidence of clinical inappropriateness of transfusion in China was estimated to be 37.3% (95% confidence interval [CI] [32.1, 42.8]). The subgroup analyses revealed that the pooled rates of clinical inappropriateness of transfusion of plasma, red blood cells (RBCs), cryoprecipitate, and platelets were 56.3% (95% CI [45.8, 66.2]), 30.9% (95% CI [27.1, 35.0]), 25.2% (95% CI [13.2, 42.7]), and 14.1% (95% CI [8.8, 21.9]), respectively. However, the pooled incidence of inappropriateness of transfusion in operative departments was 47.5% (95% CI [36.8, 58.3]), which was significantly higher than that in nonoperative departments, 25.8% (95% CI [18.7, 34.4], P < 0.05). The overall rates of inappropriate use were 36.7% (95% CI [30.2, 43.6]) in major cities and 37.5% (95% CI [31.2, 44.3]) in other cities, respectively; there was no statistically significant difference (P > 0.05). In conclusion, China has suffered from a disadvantage in the clinical appropriateness of blood transfusion, especially in plasma and RBC use. In future, comprehensive measures should be implemented in order to improve the clinical appropriateness of blood transfusion. PMID- 26683926 TI - Serum Gamma-Glutamyltransferase Levels are Associated With Concomitant Cardiovascular Risk Factors in Korean Hypertensive Patients: A Nationwide Population-Based Study. AB - Previous studies suggested that serum gamma-glutamyltransferase (GGT) levels were associated with the prevalence of cardiovascular disease (CVD) risk factors including hypertension, diabetes mellitus (DM), and metabolic syndrome (MetS) in the general population. We aimed to investigate the relationship between serum GGT levels and CVD risk factors in Korean hypertensive patients. This cross sectional study was based on data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2011 to 2012. The analysis included 1541 hypertensive participants. Study participants were divided into groups according to tertiles of serum GGT with cutoff points of 20 and 35 U/L. Serum GGT levels were positively associated with the components of MetS (P value < 0.05, except for systolic blood pressure and high-density lipoprotein cholesterol). After adjusting for possible confounders, serum GGT levels were associated with an increased risk of MetS, high waist circumference, high triglyceride level, fasting plasma glucose, DM, and the urinary albumin-to-creatinine ratio (P = 0.001). In hypertensive patients, serum GGT levels are positively associated with major cardiovascular risk factors such as MetS, DM, and urinary albumin excretion. PMID- 26683927 TI - Can Vitamin D Supplementation in Addition to Asthma Controllers Improve Clinical Outcomes in Patients With Asthma?: A Meta-Analysis. AB - Effects of vitamin D on acute exacerbation, lung function, and fraction of exhaled nitric oxide (FeNO) in patients with asthma are controversial. We aim to further evaluate the roles of vitamin D supplementation in addition to asthma controllers in asthmatics. From 1946 to July 2015, we searched the PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials, and ISI Web of Science using "Vitamin D," "Vit D," or "VitD" and "asthma," and manually reviewed the references listed in the identified articles. Randomized controlled trials which reported rate of asthma exacerbations and adverse events, forced expiratory volume in 1 s (FEV1, % of predicted value), FeNO, asthma control test (ACT), and serum 25-hydroxyvitamin D levels were eligible. We conducted the heterogeneities test and sensitivity analysis of the enrolled studies, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference for dichotomous and continuous data, respectively. Cochrane systematic review software Review Manager (RevMan) was used to test the hypothesis by Mann-Whitney U test, which were displayed in Forest plots. Seven trials with a total of 903 patients with asthma were pooled in our final studies. Except for asthma exacerbations (I2 = 81%, chi2 = 10.28, P = 0.006), we did not find statistical heterogeneity in outcome measures. The pooled RR of asthma exacerbation was 0.66 (95% confidence interval: 0.32-1.37), but without significant difference (z = 1.12, P = 0.26), neither was in FEV1 (z = 0.30, P = 0.77), FeNO (z = 0.28, P = 0.78), or ACT (z = 0.92, P = 0.36), although serum 25-hydroxyvitamin D was significantly increased (z = 6.16, P < 0.001). Vitamin D supplementation in addition to asthma controllers cannot decrease asthma exacerbation and FeNO, nor improve lung function and asthma symptoms, although it can be safely applied to increase serum 25-hydroxyvitamin D levels. PMID- 26683928 TI - Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection. AB - Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV-) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection. For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed. p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39-0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66-1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16+ and p16- groups. A region containing PRDM2 was amplified only in the p16+ group, whereas EGFR and 11q13.3 showed increased amplification in p16- counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16+ OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS. p16+ OSCC exhibit distinct CNV patterns compared with p16- counterpart. Specific patterns of CNVs predict better survival, especially in p16+ OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV- OSCC. PMID- 26683929 TI - Gender and Age Impacts on the Association Between Thyroid Function and Metabolic Syndrome in Chinese. AB - The relationship between thyroid dysfunction and metabolic syndrome (MS) is complex. We aimed to explore the impact of gender and age on their association in a large Chinese cohort. This cross-sectional study enrolled 13,855 participants (8532 male, 5323 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and serum metabolic parameters were collected. The associations between thyroid function and MS of both genders were analyzed separately after dividing thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and age into subgroups. MS risks were calculated by binary logistic regression models. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher prevalence than males. Females had higher incidence of thyroid dysfunction than males. By using TSH quartiles as the categorical variables and the lowest quartile as reference, significantly increased MS risk was demonstrated in quartile 4 for males, yet quartiles 3 and 4 for females. By using FT3 quartiles as the categorical variables, significantly increased MS risk was demonstrated in quartile 2 to 4 for females only. By using age subgroups as the categorical variables, significantly increased MS risk was shown in both genders, with females (4.408-58.455) higher than males (2.588-4.943). Gender and age had substantial influence on thyroid function and MS. Females with high TSH and high FT3 had higher MS risks than males. Aging was a risk for MS, especially for females. Urgent need is necessary to initiate interventional programs. PMID- 26683930 TI - Acute and Chronic Pheochromocytoma-Induced Cardiomyopathies: Different Prognoses?: A Systematic Analytical Review. AB - Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies. We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms "myocarditis," "myocardial infarction," "Takotsubo," "stress cardiomyopathy," "cardiogenic shock", or "dilated cardiomyopathy," and "pheochromocytoma" or "paraganglioma" from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed. A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs 73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03-0.67], P = 0.03). Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG. PMID- 26683931 TI - Corneal Complications During and After Vitrectomy for Retinal Detachment in Photorefractive Keratectomy Treated Eyes. AB - To evaluate the occurrence of late-onset corneal haze (LOCH) after vitrectomy for rhegmatogenous retinal detachment (RRD) in photorefractive keratectomy (PRK) treated eyes. This observational cohort study comprised 13 eyes of 13 patients who underwent vitrectomy for RRD and who had been subjected to PRK years earlier. The occurrence of LOCH was evaluated together with all the preoperative, intraoperative, and postoperative factors that could affect final corneal status. LOCH developed in 2 eyes. Both patients had undergone PRK for high myopia--one 3 years and the other 9 years prior to RRD. Both patients presented with RRD due to giant retinal tear and were subjected to scleral buckle, 20-gauge vitrectomy, and silicone oil tamponade. Three months after vitrectomy and 1 month after silicone oil removal they both developed LOCH. During vitreoretinal surgery neither of the 2 patients needed mechanical epithelial debridement. Intraoperative epithelial debridement was performed in 2 of the other patients of the series, who had undergone previous PRK for high myopia and had clear corneas at presentation; in 1 of them this manoeuvre hampered intraoperative visualization. Follow-up after retinal detachment surgery ranged from 6 to 156 months (mean, 37.5 months). Subepithelial corneal scarring may be reactivated many years after PRK. In our series this happened after vitrectomy. PMID- 26683932 TI - Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain: A PRISMA Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - Advantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood. To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain. PubMed, Embase, and the Cochrane Library were searched through July 2015. Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain. Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity. Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08-1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, -0.50-1.40; P < 0.00001) or complication rate (RR 1.10; 95% CI, 0.26-4.58; P = 0.29). Meta-analysis was not performed for NSAIDs injection due to considerable heterogeneity. Conflicting results were observed in favor of either steroid or NSAIDs injection. Not all diseases that can lead to shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results. Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at 4 to 6 weeks. Treatment decision should be made based on diseases. NSAIDs injection might be a treatment method for shoulder pain. PMID- 26683933 TI - Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept. AB - Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D "bone-like" structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6% 20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote osteogenesis in extreme conditions of bone nonunions with minor donor site morbidity and no oncological side effects. PMID- 26683935 TI - Diagnostic Performance of Self-Assessment for Constipation in Patients With Long Term Opioid Treatment. AB - Constipation is a prevalent comorbidity affecting ~50% of patients with long-term opioid therapy. In clinical routine different diagnostic instruments are in use to identify patients under risk. The aim of this study was to assess the diagnostic performance of an 11-item Likert scale for constipation used as a self assessment in opioid-treated patients. This trial was conducted as a retrospective cohort study in Berlin, Germany. Patients with long-term opioid therapy treated in 2 university-affiliated outpatient pain facilities at the Charite hospital were included from January 2013 to August 2013. Constipation was rated in a self-assessment using a numeric rating scale from 0 to 10 (Con-NRS) and compared with results from a structured assessment based on ROME-III criteria. Altogether, 171 patients were included. Incidence of constipation was 49% of patients. The receiver-operating characteristic of Con-NRS achieved an area under the curve of 0.814 (AUC 95% confidence interval 0.748-0.880, P < 0.001). Con-NRS >= 1 achieved sensitivity and specificity of 79.7% and 77.2%, respectively. The positive predictive value and the negative predictive value were 70.3% and 81.6%, respectively. Overall diagnostic performance of a concise 11-item Likert scale for constipation was moderate. Although patients with long term opioid therapy are familiar with numeric rating scales, a significant number of patients with constipation were not identified. The instrument may be additionally useful to facilitate individualized therapeutic decision making and to control therapeutic success when measured repetitively. PMID- 26683934 TI - High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor. AB - There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery. For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by >=2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data. Eight miRNAs (miRNA-27b, -122, -142-5p, -196a, -223, -590 5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732-153.789; P = 0.015). MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required. PMID- 26683936 TI - PCDH10 Interacts With hTERT and Negatively Regulates Telomerase Activity. AB - Telomerase catalyzes telomeric DNA synthesis, an essential process to maintain the length of telomere for continuous cell proliferation and genomic stability. Telomerase is activated in gametes, stem cells, and most tumor cells, and its activity is tightly controlled by a catalytic human telomerase reverse transcriptase (hTERT) subunit and a collection of associated proteins. In the present work, normal human testis tissue was used for the first time to identify proteins involved in the telomerase regulation under normal physiological conditions. Immunoprecipitation was performed using total protein lysates from the normal testis tissue and the proteins of interest were identified by microfluidic high-performance liquid chromatography and tandem mass spectrometry (HPLC-Chip-MS/MS). The regulatory role of PCDH10 in telomerase activity was confirmed by a telomeric repeat amplification protocol (TRAP) assay, and the biological functions of it were characterized by in vitro proliferation, migration, and invasion assays. A new in vivo hTERT interacting protein, protocadherin 10 (PCDH10), was identified. Overexpression of PCDH10 in pancreatic cancer cells impaired telomere elongation by inhibiting telomerase activity while having no obvious effect on hTERT expression at mRNA and protein levels. As a result of this critical function in telomerase regulation, PCDH10 was found to inhibit cell proliferation, migration, and invasion, suggesting a tumor suppressive role of this protein. Our data suggested that PCDH10 played a critical role in cancer cell growth, by negatively regulating telomerase activity, implicating a potential value in future therapeutic development against cancer. PMID- 26683937 TI - Effectiveness and Safety of Warfarin in Dialysis Patients With Atrial Fibrillation: A Meta-Analysis of Observational Studies. AB - In routine practice, warfarin is widely used in dialysis patients with atrial fibrillation (AF) for stroke prevention though the ratio of risks to benefits remains unclear. Recent cohort studies investigating the association between warfarin use and the risks of stroke and bleeding in dialysis patients with AF present conflicting results. The objective of this study was to assess the effectiveness and safety of warfarin use in patients with AF undergoing dialysis. Three databases PubMed, EMBASE, and OVID were searched from their inception to August 2015. Observational studies which assessed the ischemic stroke or bleeding risk of warfarin use in dialysis patients with AF were included. Two reviewers independently extracted data and assessed methodological quality based on the Newcastle-Ottawa Scale score. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model and heterogeneity was assessed based on the Cochrane Q-statistic test and the I statistic. Metaregression analyses were performed to explore the source of heterogeneity. A total of 11 eligible studies with 25,407 patients were included in the analysis. Warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for ischemic stroke (HR 0.95, 95% CI 0.66-1.35). Sensitivity analyses found results to be robust. Metaregression analysis showed that demographic feature, clinical characteristics, or study-level variable had no impact of warfarin use on stroke risk. In addition, warfarin use was associated with a 27% higher risk for bleeding (95% CI 1.04-1.54). Overall, warfarin use did not have a significant association with reduced mortality (95% CI 0.96-1.11). It appears that warfarin use is not beneficial in reducing stroke risk, but with a high risk for bleeding in dialysis patients with AF. Randomized trials are needed to determine the risk-benefit ratio of warfarin in dialysis patients with AF. PMID- 26683938 TI - A Case Report of an Elderly Woman With Thrombocytopenia and Bilateral Lung Infiltrates: A Rare Association Between Diffuse Alveolar Hemorrhage and Idiopathic Thrombocytopenic Purpura. AB - Etiologies for diffuse alveolar hemorrhage are wide and range from infectious to vasculitis and malignant processes. Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by persistent thrombocytopenia, with a relatively indolent course in young patients, but a more complicated progression and high associated mortality in the older patients. Diffuse alveolar hemorrhage, complicating idiopathic thrombocytopenic purpura, is a very uncommon association, with only 2 reported cases in the literature. We present a 69-year-old healthy woman presenting with petechial rash, progressive dyspnea, and bilateral alveolar infiltrates. She was found to have idiopathic thrombocytopenic purpura associated with diffuse alveolar hemorrhage. The patient had an excellent response to high doses of pulse steroids and immunoglobulins. A high index of suspicion for noninfectious pulmonary diseases should be considered in patients with autoimmune diseases presenting with pulmonary infiltrates and hypoxia. Flexible bronchoscopy with sequential lavage is a relatively safe procedure in patients with coagulopathy and should be attempted to detect and confirm the diagnosis; absence of hemoptysis should not preclude the diagnosis. PMID- 26683939 TI - Baseline, Trend, and Normalization of Carcinoembryonic Antigen as Prognostic Factors in Epidermal Growth Factor Receptor-Mutant Nonsmall Cell Lung Cancer Patients Treated With First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. AB - Among epidermal growth factor receptor (EGFR) mutation status unknown nonsmall cell lung cancer (NSCLC) patients, those with higher carcinoembryonic antigen (CEA) level are more likely to response to EGFR-tyrosine kinase inhibitors (TKIs) because they tend to have mutant epidermal growth factor receptor (EGFR). However, patients with higher CEA also have more tumor burden. With the above paradoxical evidence, it is prudent to understand the prognostic significance of baseline CEA in patients with EGFR-mutant NSCLC treated with first-line EGFR TKIs. The clinical significance of the trend in CEA after treatment and the impact of CEA normalization during EGFR-TKI therapy are also unknown and potentially important. A total of 241 patients who received first-line EGFR-TKIs were included. As to baseline CEA, patients were divided into normal, low, and high baseline CEA by cut point determined by receiver operating characteristic curves. As to CEA responses, patients were divided into 3 groups accordingly to their amount of CEA change after taking TKIs. In group A, 1-month follow-up CEA level decreased more than 35% with nadir CEA normalization; in group B, 1-month follow-up CEA level decreased more than 35% without nadir CEA normalization; and in group C, 1-month follow-up CEA level decreased less than 35% or increased. Patients with higher baseline CEA levels had shorter progression-free survival (PFS) and overall survival (OS) (CEA > 32 vs 5-32 vs <5 ng/mL, PFS = 8.8 vs 11.3 vs 14.4 months, respectively, P < 0.001; OS = 17.8 vs 22.0 vs 27.9 months, respectively, P = 0.01). For trend and CEA normalization in groups A, B, and C, PFS was 14.3, 10.6, and 7.1 months, respectively (P < 0.001); OS was 29.7, 20.0, and 16.2 months, respectively (P < 0.001). Baseline, trend, and normalization of CEA levels are potential prognostic markers for patients with EGFR-mutant advanced NSCLC treated with first line EGFR-TKIs. PMID- 26683940 TI - Impact of Age on Stent Strut Coverage and Neointimal Remodeling as Assessed by Optical Coherence Tomography. AB - While older age associates with adverse percutaneous coronary intervention (PCI) outcomes, detailed information relating age to stent strut coverage and neointimal characteristics is lacking. One hundred nineteen patients with 123 sirolimus-eluting stents (SESs) were divided into 3 groups: group A (<=55 years), group B (56-65 years), and group C (>65 years). At 6 and 12 months of follow-up, optical coherence tomography was performed to assess strut coverage and neointimal remodeling. At 6 months, the proportion of uncovered struts increased with age: 6.1% in group A versus 7.3% in group B versus 11.7% in group C (P < 0.001) while the proportion of embedded struts decreased: 72.1% versus 57.0% vs. 55.0%, respectively (P < 0.001). Mean neointimal thicknesses were 90 MUm versus 60 MUm versus 60 MUm, respectively (P < 0.001), and neointimal areas were 0.82 mm2 versus 0.52 mm2 versus 0.57 mm2 (P < 0.001). At 12 months, the proportion of uncovered struts increased with age (3.9% vs. 3.3% vs. 4.9 %; P < 0.001), while mean neointimal thicknesses were 100 versus 70 versus 80 MUm (P < 0.001) and neointimal areas were 0.87 versus 0.60 versus 0.67 mm2 (P < 0.001). Patients <=55 years receiving SES showed highest strut coverage and neointimal repair rate compared with the other 2 groups. A "catch-up phenomenon" appeared to occur in the oldest patients, as in the first 6 months the neointima showed lowest endothelial cell coverage and lowest neointimal proliferation rate, whereas from 6 to 12 months, the highest neointimal proliferation rate was seen in the oldest patients. PMID- 26683941 TI - Diagnostic Value of SLC26A4 Mutation Status in Hereditary Hearing Loss With EVA: A PRISMA-Compliant Meta-Analysis. AB - Many SLC26A4 mutations have been identified in patients with nonsyndromic enlarged vestibular aqueduct (EVA). However, the roles of SLC26A4 genotypes and phenotypes in hereditary deafness remain unexplained. This study aims to perform a meta-analysis based on the PRISMA statement to evaluate the diagnostic value of SLC26A4 mutant alleles and their correlations with multiethnic hearing phenotypes in EVA patients. The systematic literature search of the PubMed, Wiley Online Library, EMBASE, Web of Science, and Science Direct databases was conducted in English for articles published before July 15, 2015. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by discussion and a third investigator. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale. Data were synthesized using random-effect or fixed-effect models. The effect sizes were estimated by measuring odds ratios (ORs) with 95% confidence interval (CI). Twenty-five eligible studies involved 2294 cases with EVA data. A total of 272 SLC26A4 variations were found in deafness with EVA and 26 mutations of SCL26A4 had higher frequency. The overall OR was 646.71 (95% CI: 383.30-1091.15, P = 0.000). A total of 22 mutants were considered statistically significant in all ethnicities (ORs >1, P < 0.05). In particular, 8 mutants were specificity of EVA phenotypes in mutations of SLC26A4 for Asia deafness populations (ORs >1, P < 0.05), 4 mutants for Europe and North America (ORs >1, P < 0.05), and the IVS7 2A>G mutations in SLC26A4 were found to have the highest frequency in deafness individuals with EVA phenotype (62.42%). Moreover, subgroups for studies limited to cases with EVA phenotype, 11 mutants relevant risks (RRs) were P < 0.05, especially for IVS7-2A>G bi-allelic mutants assayed in a deafness population (RR = 0.880, P = 0.000). Diagnostic accuracy of SLC26A4 mutation results also identified the significant association of IVS7-2A>G (AUC = 0.99, 95% CI: 0.97 0.99) and p.H723R (AUC = 0.99, 95% CI: 0.98-1.00) detecting deafness with EVA. To conclude, the IVS7-2A>G and H723R in SLC26A4 present a significant predicting value and discriminatory ability for clinical use on diagnosis of EVA within a deafness population. PMID- 26683942 TI - Selective Inflow Occlusion Technique Versus Intermittent Pringle Maneuver in Hepatectomy for Large Hepatocellular Carcinoma: A Retrospective Study. AB - Selective inflow occlusion (SIO) maneuver preserved inflow of nontumorous liver and was supposed to protect liver function. This study aims to evaluate whether SIO maneuver is superior to Pringle maneuver in patients undergoing partial hepatectomy with large hepatocellular carcinomas (HCCs). Between January 2008 and May 2012, 656 patients underwent large HCC resections and were divided into 2 groups: intermittent Pringle maneuver (IP) group (n = 336) and SIO group (n = 320). Operative parameters, postoperative laboratory tests, and morbidity and mortality were analyzed. In comparison to the IP maneuver, the SIO maneuver significantly decreased intraoperative blood loss (473 vs 691 mL, P = 0.001) and transfusion rates (11.3% vs 28.6%, P = 0.006). The rate of major complication between the 2 groups was comparable (22.6% vs 18.8%, P = 0.541). Patients with moderate/severe cirrhosis, total bilirubin > 17 MUmol/L, or HBV DNA> = 104 copy/mL in SIO group resulted in lower major complication rates. The SIO maneuver is a safe and effective technique for large HCC resections. In patients with moderate/severe cirrhosis, total bilirubin > 17 MUmol/L, or HBV DNA> = 104 copy/mL, the SIO technique is preferentially recommended. PMID- 26683943 TI - Concurrent Intervention With Exercises and Stabilized Tumor Necrosis Factor Inhibitor Therapy Reduced the Disease Activity in Patients With Ankylosing Spondylitis: A Meta-Analysis. AB - Since the use of tumor necrosis factor (TNF) inhibitor therapy is becoming wider, the effects of concurrent intervention with exercises and stabilized TNF inhibitors therapy in patients with ankylosing spondylitis (AS) are different. The study aimed to objectively evaluate whether concurrent intervention with exercises and stabilized TNF inhibitors can reduce the disease activity in patients with AS. A search from PubMed, Web of Science, EMBASE, and the Cochrane Library was electronically performed to collect studies which compared concurrent intervention with exercise and TNF inhibitor to conventional approach in terms of disease activity in patients with AS published from their inception to June 2015. Studies that measured the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), and chest expansion as outcomes were included. Two independent investigators screened the identified articles, extracted the data, and assessed the methodological quality of the included studies. Quantitative analysis was performed with Review Manager (RevMan) software (version 5.3.0). A total of 5 studies comprising 221 participants were included in the study. Meta-analyses showed that concurrent intervention with exercises and stabilized TNF inhibitors therapy significantly reduced the BASMI scores (MD, -0.99; 95% CI, -1.61 to -0.38) and BASDAI scores (MD, -0.58; 95% CI, 1.10 to -0.06), but the BASFI scores (MD, -0.31; 95% CI, -0.76 to 0.15) was not reduced, and chest expansion (MD, 0.80; 95% CI, -0.18 to 1.78) was not increased. Concurrent intervention with exercises and stabilized TNF inhibitors therapy can reduce the disease activity in patients with AS. More randomized controlled trials (RCTs) with high-quality, large-scale, and appropriate follow-up are warranted to further establish the benefit of concurrent intervention with exercises and TNF inhibitors for this given population due to some limitations impaired the power of our study. PMID- 26683944 TI - Radiofrequency Ablation Versus Partial Nephrectomy in Treating Small Renal Tumors: A Systematic Review and Meta-Analysis. AB - Radiofrequency ablation (RFA) has emerged as an alternative treatment to surgical partial nephrectomy (PN) in the treatment of small renal tumors (SRTs). But its safety and oncological efficacy are still controversial. We conducted this systematic review and meta-analysis to compare the peritoperative and oncological outcomes of RFA and PN in the treatment of SRTs. Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science were searched to identify eligible studies that compared the RFA and PN in the treatment of SRTs. Twelve retrospective studies that compared RFA with PN in the treatment of SRTs met our selection criterion and were included in this meta-analysis. The pooled results indicated that the local recurrence rate (4.14% vs 4.10%, RR: 1.18, 95% CI: 0.68, 2.07, P = 0.550) and distant metastases rate (2.76% vs 1.89%, RR: 1.31, 95% CI: 0.70, 2.46, P = 0.686) were not significantly different between the RFA group and the PN group. In terms of perioperative outcomes, RFA was associated with shorter length of stay (LOS) (WMD: -2.02 days, 95% CI: -2.77, -1.27, P < 0.001), lower eGFR decline after treatment (WMD: -3.90, 95% CI: -6.660, -1.140, P = 0.006). However, the overall perioperative complication rate (7.5% vs 6.2%, RR:1.10, 95% CI: 0.64, 1.87, P = 0.740) and the major complication rate (3.7% vs 4.4%, RR: 0.83, 95% CI: 0.43, 1.60, P = 0.579) were both similar between RFA and PN groups. Compared with PN, RFA achieves an equal oncological outcome for SRTs with similar local recurrence rate and distant metastases rate. Additionally, RFA is associated with a similar perioperative complication rate, lower decline of eGFR, and shorter LOS. Therefore, RFA is an effective option in the treatment of SRTs for selected patients. PMID- 26683945 TI - Is Pathologic Near-Total Regression an Appropriate Indicator of a Good Response to Preoperative Chemoradiotherapy Based on Oncologic Outcome of Disease? AB - We evaluated the oncologic outcomes of patients with rectal cancer who demonstrated pathologic near-total regression (NTR) after preoperative chemoradiotherapy (PCRT) and compared with total regression (TR). Pathologic NTR in rectal cancer by tumor regression grade (TRG) is usually considered to indicate a good response, when evaluating tumor response to PCRT. We retrospectively analyzed the outcomes in 263 patients who received PCRT for advanced T3/4 or N+ rectal cancer followed by radical resection. Patients were diagnosed with TR (n = 132) or NTR (n = 131) according to the TRG. Recurrence free survival (RFS) was evaluated and compared between groups. For evaluating the consistency between the result and previously published data, meta-analysis for summing up survival curve was performed using generalized linear mixed model. ypT status was heterogeneous in the NTR group as follows; 3 Tis (2.3%), 21 T1 (16%), 72 T2 (55%), and 35 T3 (26.7%). Metastatic lymph nodes were more frequently found in the NTR group (6.8% in TR vs 24.4% in NTR patients; P = 0.003). The cumulative recurrence rate was higher in the NTR group (19.8% vs 6.1%; P = 0.003). The 5 year RFS was lower in the NTR group (94% vs 77.8%; P = 0.001). Significant differences in the RFS rate were found in comparison with the published literature. Based on differences in the oncologic outcomes between the TR and NTR groups, it might not be suitable to use NTR as an indicator of good response to PCRT together with TR. PMID- 26683946 TI - Relationship Between the Urine Flow Rate and Risk of Contrast-Induced Nephropathy After Emergent Percutaneous Coronary Intervention. AB - A low urine flow rate is a marker of acute kidney injury. However, it is unclear whether a high urine flow rate is associated with a reduced risk of contrast induced nephropathy (CIN) in high-risk patients. We conducted this study to evaluate the predictive value of the urine flow rate for the risk of CIN following emergent percutaneous coronary intervention (PCI). We prospectively examined 308 patients undergoing emergent PCI who provided consent. The predictive value of the 24-hour postprocedural urine flow rate, adjusted by weight (UR/W, mL/kg/h) and divided into quartiles, for the risk of CIN was assessed using multivariate logistic regression analysis. The cumulative incidence of CIN was 24.4%. In particular, CIN was observed in 29.5%, 19.5%, 16.7%, and 32.0% of cases in the UR/W quartile (Q)-1 (<=0.94 mL/kg/h), Q2 (0.94 1.30 mL/kg/h), Q3 (1.30-1.71 mL/kg/h), and Q4 (>=1.71 mL/kg/h), respectively. Moreover, in-hospital death was noted in 7.7%, 3.9%, 5.1%, and 5.3% of patients in Q1, Q2, Q3, and Q4, respectively. After adjusting for potential confounding predictors, multivariate analysis indicated that compared with the moderate urine flow rate quartiles (Q2 + Q3), a high urine flow rate (Q4) (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.27-5.68; P = 0.010) and low urine flow rate (Q1) (OR, 2.23; 95% CI, 1.03-4.82; P = 0.041) were significantly associated with an increased risk of CIN. Moreover, a moderate urine flow rate (0.94-1.71 mL/kg/h) was significantly associated with a decreased risk of mortality. Our data suggest that higher and lower urine flow rates were significantly associated with an increased risk of CIN after emergent PCI, and a moderate urine flow rate (0.94-1.71 mL/kg/h) may be associated with a decreased risk of CIN with a good long-term prognosis after emergent PCI. PMID- 26683947 TI - Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer. AB - Although microsatellite instability-high (MSI-H) colorectal cancers (CRCs) have been shown to exhibit a distinct phenotype, the clinical value of MSI-low (MSI-L) in CRC remains unclear. We designed this study to examine the clinicopathologic characteristics and oncologic implications associated with MSI-L CRCs. We retrospectively reviewed data of CRC patients from 3 tertiary referral hospitals in Korea, who underwent surgical resection between January 2003 and December 2009 and had available MSI testing results. MSI testing was performed using the pentaplex Bethesda panel. Clinicopathologic features and oncologic outcomes were compared between MSI-L and microsatellite stable (MSS) CRCs; prognostic factors for survival were also examined. Of the 3019 patients reviewed, 2621 (86.8%) were MSS, and 200 (6.6%) were MSI-L; the remaining 198 (6.6%) were MSI-H. MSI-L and MSS CRCs were comparable in terms of their clinicopathologic features, with the exception of proximal tumor location (MSI-L 30.0% vs MSS 22.1%, P = 0.024) and tumor size (MSI-L 5.2 +/- 2.6 cm vs MSS 4.6 +/- 2.1 cm, P = 0.001). No differences were detected in either 3-year disease-free survival (MSI-L 87.2% vs MSS 82.6%, P = 0.121) or 5-year overall survival (OS) (MSI-L 74.2% vs MSS 78.3%, P = 0.131) by univariable analysis. However, MSI-L was an independent prognostic factor for poor OS by Cox regression analysis (hazard ratio 1.358, 95% confidence interval 1.014-1.819, P = 0.040). MSI-L may be an independent prognostic factor for OS in sporadic CRCs despite their clinicopathologic similarity to MSS. Further studies investigating the significance of MSI-L in the genesis and prognosis of CRCs are needed. PMID- 26683948 TI - Ultrasound-Guided Versus Fluoroscopy-Guided Caudal Epidural Steroid Injection for the Treatment of Unilateral Lower Lumbar Radicular Pain: Case-Controlled, Retrospective, Comparative Study. AB - The aim of the article is to investigate the efficacy of ultrasound (US)-guided Caudal Epidural Steroid Injection (CESI) compared with fluoroscopy (FL)-guided CESI in patients with unilateral lower lumbar radicular pain. This case controlled, retrospective, comparative study was done at the university hospital. A total of 110 patients treated with US- or FL-guided CESI were administered a mixture of 20 cc (0.5% lidocaine 18.0 mL + dexamethason 10 mg 2 mL). Outcome measurement was assessed by Oswestry Disability Index (ODI), verbal numeric pain scale (VNS) before injections and at 3, 6, and 12 months after the last injections. Successful outcome was defined as measured by >50% improvement in the VNS score and >40% improvement in the ODI. ODI and VNS showed improvement at 3, 6, and 12 months after the last injection in both groups. No statistical differences in ODI, VNS were observed between groups (P < 0.05). No significant differences in the proportion of patients with successful treatment were observed between the groups from the 3-month to 6-month to 12-month outcomes. US-guided CESI is deserving of consideration in conservative management of unilateral lower lumbar radicular pain. PMID- 26683949 TI - Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole: A Prospective, Randomized, Controlled Trial. AB - This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation, simultaneously administering clopidogrel, atorvastatin, and lansoprazole did not decrease the antiplatelet efficacy of clopidogrel or increase adverse event frequency over 6 months. PMID- 26683950 TI - HIV-Related Medical Admissions to a South African District Hospital Remain Frequent Despite Effective Antiretroviral Therapy Scale-Up. AB - The public sector scale-up of antiretroviral therapy (ART) in South Africa commenced in 2004. We aimed to describe the hospital-level disease burden and factors contributing to morbidity and mortality among hospitalized HIV-positive patients in the era of widespread ART availability. Between June 2012 and October 2013, unselected patients admitted to medical wards at a public sector district hospital in Cape Town were enrolled in this cross-sectional study with prospective follow-up. HIV testing was systematically offered and HIV-infected patients were systematically screened for TB. The spectrum of admission diagnoses among HIV-positive patients was documented, vital status at 90 and 180 days ascertained and factors independently associated with death determined. Among 1018 medical admissions, HIV status was ascertained in 99.5%: 60.1% (n = 609) were HIV-positive and 96.1% (n = 585) were enrolled. Of these, 84.4% were aware of their HIV-positive status before admission. ART status was naive in 35.7%, current in 45.0%, and interrupted in 19.3%. The most frequent primary clinical diagnoses were newly diagnosed TB (n = 196, 33.5%), other bacterial infection (n = 100, 17.1%), and acquired immunodeficiency syndrome (AIDS)-defining illnesses other than TB (n = 64, 10.9%). By 90 days follow-up, 175 (29.9%) required readmission and 78 (13.3%) died. Commonest causes of death were TB (37.2%) and other AIDS-defining illnesses (24.4%). Independent predictors of mortality were AIDS-defining illnesses other than TB, low hemoglobin, and impaired renal function. HIV still accounts for nearly two-thirds of medical admissions in this South African hospital and is associated with high mortality. Strategies to improve linkage to care, ART adherence/retention and TB prevention are key to reducing HIV-related hospitalizations in this setting. PMID- 26683951 TI - The Seroprevalence of Toxoplasma gondii in Chinese Population With Cancer: A Systematic Review and Meta-analysis. AB - Toxoplasmosis is fatal in the immunocompromised individuals such as cancer patients with chemotherapy. Clinical toxoplasmosis in cancer patients is a great public health concern in China. We performed this meta-analysis to assess the seroprevalence and odds ratios (ORs) of Toxoplasma gondii in Chinese population with cancer compared with those without. A methodical literature search was conducted with the help of the PubMed, Web of Knowledge, Embase, Chinese Web of Knowledge, Wanfang, and Chongqing VIP database. Case-control studies published from their inception until April 2015, reporting the seroprevalence of T. gondii in Chinese population with cancer, were covered as well. The nonweighted prevalence, pooled random-effects estimates of ORs, and 95% confidence intervals (CIs) were all calculated. Nineteen studies including 4493 cases and 6797 controls were incorporated in the meta-analysis. The overall seroprevalence of T. gondii was higher in population with cancer compared with those without ((20.59% vs 6.31%, P < 0.001; OR 3.90, 95% CI 3.00-5.07). The OR of T. gondii in cancer patients is further subgrouped according to publication year, sample size, and diagnostic methods. The pooled OR estimates were 4.80 (95% CI 2.57-8.99) from 1991 to 1999, 4.96 (95% CI 3.03-8.12) during 2000 to 2005, and 2.94 (95% CI 2.46 3.50) during 2006 to 2015. The pooled OR estimates were 6.16 (95% CI 3.87-9.78) when the sample size was below 400, 5.37 (95% CI 3.84-7.53) when the sample size was between 400 and 500, and 2.58 (95% CI 2.17-3.07) when the sample size was above 500. The pooled OR estimates were 5.50 (95% CI 3.98-7.62) by using indirect hemagglutination assay method, and 3.15 (95% CI 2.67-3.72) by using enzyme-linked immunosorbent assay method. The meta-analysis study found Chinese population with cancer had higher seroprevalence rates of T. gondii compared with those without. PMID- 26683952 TI - Immune Compromise in HIV-1/HTLV-1 Coinfection With Paradoxical Resolution of CD4 Lymphocytosis During Antiretroviral Therapy: A Case Report. AB - Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity. PMID- 26683953 TI - Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study. AB - The effect of hepatitis B virus (HBV) infection on bone mineral density in patients without advanced liver disease remains unclear. Hence, we assessed the association between HBV infection and the risk of osteoporosis. From 2000 to 2011, patients older than 20 years with HBV infection were identified from the Longitudinal Health Insurance Database 2000. Of the 180,730 sampled patients, 36,146 and 144,584 patients were categorized into HBV infection and comparison cohorts, respectively. Compared with the comparison cohort, the HBV infection patients had a higher risk of osteoporosis (adjusted hazard ratio [aHR]: 1.14, 95% confidence interval [CI]: 1.03-1.25) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and estrogen replacement therapy. The patients with HBV infection exhibited a 1.13-fold (95% CI = 1.03-1.25) higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV infection and the comparison cohort (aHR = 1.20, 95% CI = 0.77-1.86). The incidence of osteoporosis increased with the increment of age (age <= 49: aHR = 1; age 50-64: aHR = 5.67, 95% CI = 5.09-6.32; age ? 65: aHR = 13.3, 95% CI = 11.8-14.9) and coexisting cirrhosis (aHR = 1.62, 95% CI = 1.24 2.12). However, the osteoporosis risk contributed by HBV infection decreased with age and the age-specific risk analyses showed that patients with HBV infection exhibited the highest risk of osteoporosis than patients without HBV infection for the patients aged <=49 (aHR = 1.42, 95% CI = 1.19-1.70). Furthermore, the osteoporosis risk contributed by HBV infection has decreased with the presence of comorbidity (aHR = 1.27, 95% CI = 1.09-1.48 vs aHR = 1.04, 95% CI = 0.91-1.15). HBV increases the risk of osteoporosis, but HBV infection may be less influential than other risk factors. Moreover, HBV has no detrimental effect on osteoporotic fracture in this study. PMID- 26683954 TI - Comparisons of Clinical Outcomes and Prognoses in Patients With Gastroesophageal Junction Adenocarcinoma, by Transthoracic and Transabdominal Hiatal Approaches: A Teaching Hospital Retrospective Cohort Study. AB - To compare the clinical outcomes and prognoses in patients with gastroesophageal junction adenocarcinoma (Siewert type II/III), by transthoracic and transabdominal hiatal approaches. Siewert II/III gastroesophageal junction adenocarcinomas patients (334 cases) underwent different surgical procedures at the Affiliated Hospital of Qingdao University from July 2007 to July 2012 and were analyzed retrospectively. In total, 140 patients underwent surgery by the transthoracic approach, and 194 patients underwent the transabdominal hiatal approach mainly with radical total and proximal gastrectomy (D2). All patients were followed up by telephone review or by outpatient reexamination until July 2013. The surgically related and clinical outcomes were compared using the chi2 test, t test, Fisher exact test, or nonparametric rank sum test according to different data. The survival curve was drawn by the Kaplan-Meier method and survival analysis used Cox regression analysis. The operative time, length of resected esophagus, number of lymph nodes harvested, postoperative pain scores, postoperative hospital stay, time of antibiotics use, postoperative morbidity, and costs for the transabdominal surgery group were better than that of the transthoracic group. The overall 5-year survival rate was 35.3% and 40.3%, respectively, in the transthoracic and transabdominal surgery groups, and differences were not statistically significant (x2 = 2.311, P > 0.05). The hazard ratio of death for the transthoracic compared with the transabdominal approach was 1.27 (0.93-1.72, P > 0.05). According to tumor node metastasis (TNM) staging, stratification analysis showed that stage III patient overall survival rates were 25.7% and 37.2%, respectively. The differences were statistically significant (x2 = 4.127, P < 0.05). In uni- and multivariate Cox regression analysis, the hazard ratio for the transabdominal versus the transthoracic approach was 0.66 (0 43 to 0.99, P < 0.05) and 1.47 (1.05-2.06, P < 0.05), respectively. There were no significant differences of 5-year overall survival in TNM stage I and II of the Siewert II/III adenocarcinoma patients, but improved survival of TNM stage III patients undergoing transabdominal hiatal compared with transthoracic total radical and proximal gastrectomy. The short-term clinical outcomes improved with the transabdominal hiatial surgery group. PMID- 26683955 TI - Iodinated Contrast Medium Exposure During Computed Tomography Increase the Risk of Subsequent Development of Thyroid Disorders in Patients Without Known Thyroid Disease: A Nationwide Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study. AB - To investigate the association between iodinated contrast medium (ICM) exposure during computed tomography (CT) and the subsequent development of thyroid disorders in patients without known thyroid disease in Taiwan, an iodine sufficient area. We conducted a population-based cohort study by using data from 1996 to 2012 in the Taiwan National Health Insurance Research Database. A total of 33,426 patients who underwent ICM-enhanced CT were included as the study cohort. To avoid selection bias, we used propensity score and matched for the index year (defined as the year of first ICM exposure) to retrieve 33,426 patients as the comparison cohort. No patients in the 2 cohorts had any known thyroid disease before the index year. Patients with a history of amiodarone treatment or coronary angiography and those with <1 year follow-up were excluded. Participants were followed until a new diagnosis of thyroid disorder or December 31, 2011. Hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated using the Cox proportional hazards regression. An association was identified between ICM exposure and the subsequent development of thyroid disorders after adjustment for potential confounders (adjusted HR = 1.17; 95% CI: 1.07-1.29; P = 0.001). Male patients and patients' ages >=40 years in the ICM exposure cohort had a higher adjusted HR for developing thyroid disorders than did those in the non-ICM-exposure cohort. Hypothyroidism had the highest adjusted HR (HR = 1.37; 95% CI: 1.06-1.78; P < 0.05) among all thyroid disorders and had a higher risk of development or detection during >0.5-year post-ICM exposure compared with that during <=0.5-year post-ICM exposure (HR = 1.26; 95% CI: 1.01 1.58; P < 0.05). Repeated ICM exposure increased the risk of thyroid disorders in patients who accepted >1 time of ICM per year on average compared with those who accepted <=1 time per year on average (adjusted HR = 3.04; 95% CI: 2.47-3.73; P < 0.001). This study identified ICM exposure during CT as a risk factor for the subsequent development of thyroid disorders in patients without known thyroid disease, particularly in patients with repeated exposure. PMID- 26683956 TI - Soy Intake Is Associated With Lower Endometrial Cancer Risk: A Systematic Review and Meta-Analysis of Observational Studies. AB - Epidemiologic studies reporting the effect of soy intake on endometrial cancer risk conveyed conflicting results. We systematically reviewed the literature to investigate whether there was an inverse relation between dietary soy intake and endometrial cancer risk. PubMed, EMBASE, the Cochrane Library, and 4 main Chinese literature databases were searched from their inception to August 25, 2015 for both case-control studies and cohort studies that assessed the effect of soy intake on endometrial cancer risk. Study-specific most-adjusted odds ratios (ORs) or relative risks (RRs) were combined by using fixed-effects or random-effects model to calculate pooled risk estimates (REs). A total of 10 epidemiologic studies were included in this meta-analysis, including 8 case-control studies and 2 prospective cohort studies. Dietary soy intake was inversely associated with endometrial cancer risk with an overall RE of 0.81 (95% CI: 0.72, 0.91). In subgroup analyses, a statistically significant protective effect of soy intake was found for unfermented soy food (RE: 0.81, 95% CI: 0.67, 0.97), postmenopausal women (RE: 0.76, 95% CI: 0.61, 0.95), and Asian (RE: 0.79, 95% CI: 0.66, 0.95) and non-Asian population (RE: 0.83, 95% CI: 0.71, 0.96). Current evidence indicates that soy food intake is associated with lower endometrial cancer risk. Further larger cohort studies are warranted to fully clarify such an association. PMID- 26683957 TI - Risk of Coronary Artery Disease in Patients With Traumatic Intracranial Hemorrhage: A Nationwide, Population-Based Cohort Study. AB - Traumatic intracranial hemorrhage (ICH) is prevalent worldwide with long-term consequences, including disabilities. However, studies on the association of traumatic ICH with coronary artery disease (CAD) are scant. Therefore, this study explored the aforementioned association in a large-scale, population-based cohort. A total of 128,997 patients with newly diagnosed traumatic ICH and 257,994 age- and sex-matched patients without traumatic ICH from 2000 to 2010 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CAD in each cohort. Cox proportional regression models were used for evaluating the risk of CAD in patients with and without traumatic ICH and for comparing the risk between the 2 cohorts. The Kaplan-Meier analysis revealed that the cumulative incidence curves of CAD were significantly higher in patients with traumatic ICH than in those without ICH (log-rank test, P < 0.001). After adjustment for age, sex, and comorbidities, patients with traumatic ICH were associated with a higher risk of CAD compared with those without traumatic ICH (adjusted hazard ratio = 1.16, 95% confidence interval = 1.13-1.20). Compared with the general population, patients with traumatic ICH and having underlying comorbidities, including diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, chronic kidney disease, and congestive heart failure, exhibited multiplicative risks of developing CAD. This cohort study revealed an increased risk of CAD in patients with traumatic ICH. Therefore, comprehensive evaluation and aggressive risk reduction for CAD are recommended in these patients. PMID- 26683958 TI - Laparoscopic Low Anterior Resection and Eversion Technique Combined With a Nondog Ear Anastomosis for Mid- and Distal Rectal Neoplasms: A Preliminary and Feasibility Study. AB - The transanal eversion and prolapsing technique is a well-established procedure, and can ensure an adequate distal margin for patients with low rectal neoplasms. Potential leakage risks, however, are associated with bilateral dog ear formation, which results from traditional double-stapling anastomosis. The authors determined the feasibility of combining these techniques with a commercial stapling set to achieve a nondog ear (end-to-end) anastomosis for patients with mid- and distal rectal neoplasms. Patients with early-stage (c/ycT1 2N0), mid- to distal rectal neoplasms and good anal sphincter function were included in this study. Laparoscopic low anterior resection was performed with a standard total mesorectal excision technique downward to the pelvic floor as low as possible. The bowel was resected proximal to the lesion with an endoscopic linear stapler. An anvil was inserted extracorporeally into the proximal colon via an extended working pore. The distal rectum coupled with the lesion was prolapsed and everted out of the anus. The neoplasm was resected with a sufficient margin above the dentate line under direct sight. A transrectal anastomosis without dog ears was performed intracorporeally to reconstitute the continuity of the bowel. Eleven cases, 6 male and 5 female patients, were included in this study. The mean operative time was 191 (129-292) minutes. The mean blood loss was 110 (30-300) mL. The median distal margin distance from the lower edge of the lesion to the dentate line was 1.5 (0.5-2.5) cm. All the resection margins were negative. Most patients experienced uneventful postoperative recoveries. No patient had anastomotic leak. Most patients had an acceptable stool frequency after loop ileostomy closure. Our preliminary data demonstrated the safety and feasibility of achieving a sound anastomosis without risking potential anastomotic leakage because of dog ear formation. PMID- 26683959 TI - Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis. AB - Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0.187) and in gastric cancer patients with positive lymph node metastasis (ORREM = 2.37, 95% CIREM: 1.19-4.73; PREM = 0.004) and intestinal-type classification (ORREM = 2.34, 95% CIREM: 1.59-3.45; PREM = 0.767). Our findings provide evidence that MUC1 detection has a prognostic value in patients with epithelial-originated cancers, especially in NSCLC and gastrointestinal cancers. PMID- 26683960 TI - A Case Report of Renal Sympathetic Denervation for the Treatment of Polymorphic Ventricular Premature Complexes: Expanding Horizons. AB - Premature ventricular complexes are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, Armaganijan et al reported the relevance of sympathetic activation in patients with ventricular arrhythmias and suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. In this report, we describe a 32-year-old hypertensive male patient presenting with a high incidence of polymorphic premature ventricular complexes on a 24 hour Holter monitor. Beginning 1 year prior, the patient experienced episodes of presyncope, syncope, and tachycardia palpitations. The patient was taking losartan 100 mg/day, which kept his blood pressure (BP) under control, and sotalol 160 mg twice daily. Bisoprolol 10 mg/day was used previously but was not successful for controlling the episodes. The 24 hour Holter performed after the onset of sotalol 160 mg twice daily showed a heart rate ranging between 48 (minimum)-78 (average)-119 (maximum) bpm; 14,286 polymorphic premature ventricular complexes; 3 episodes of nonsustained ventricular tachycardia, the largest composed of 4 beats at a rate of 197 bpm; and 14 isolated atrial ectopic beats. Cardiac magnetic resonance imaging with gadolinium perfusion performed at rest and under pharmacological stress with dipyridamole showed increased left atrial internal volume, preserved systolic global biventricular function, and an absence of infarcted or ischemic areas. The patient underwent bilateral renal sympathetic denervation. The only drug used postprocedure was losartan 25 mg/day. Three months after the patient underwent renal sympathetic denervation, the mean BP value dropped to 132/86 mmHg, the mean systolic/diastolic 24 hour ambulatory BP measurement was reduced to 128/83 mmHg, and the 24 hour Holter monitor showed a heart rate ranging between 51 (minimum)-67 (average)-108 (maximum) bpm, 854 polymorphic premature ventricular complexes, and no episodes of nonsustained ventricular tachycardia. PMID- 26683961 TI - Prognostic Significance of Tumor Size in 2405 Patients With Gastric Cancer: A Retrospective Cohort Study. AB - The clinical prognostic significance of tumor size (Ts) in gastric cancer remains under debate. This study aims to evaluate the prognostic value of Ts in gastric cancer patients undergoing gastrectomy. A total of 2405 patients with gastric cancer, all having received radical resection, were enrolled in this retrospective study from 2000 to 2011. Patients were categorized by minimum P value from log-rank chi2 statistics using X-tile. The relationships between Ts and other clinicopathologic characteristics were analyzed, and the survival prediction accuracy was also compared between Ts and T stage. Patients were divided into 5 groups, according to which Ts stage and TsNM stage system were proposed. Ts, an independent prognostic factor identified by univariate and multivariate survival analysis, was significantly associated with sex, age, tumor location, macroscopic type, tumor diffferentiation, vessel invasion, perineural invasion, T stage, N stage, and TNM stage. Compared with T stage system, Ts stage system was found no superiorities in survival prediction. However, for patients with lymph node metastasis and patients with age >=60, Ts stage system revealed a significant improvement of predictive accuracy in subgroup survival analysis. Furthermore, TsNM stage (c-index = 0.783) system was found to be superior to TNM stage (c-index = 0.743) system in prognostic prediction accuracy (P < 0.05). Ts is significantly correlated with gastric cancer progression, which can be regarded as a reliable prognostic factor, and the TsNM stage system may improve the prognostic prediction accuracy in gastric cancer patients. PMID- 26683962 TI - Laparoscopy-Assisted Single-Port Appendectomy in Children: Safe Alternative also for Perforated Appendicitis? AB - Because of its low complication rate, favorable safety, cost-effectiveness, and technical ease, mono-instrumental, laparoscopy-assisted single-port appendectomy (SPA) has been the standard therapy for appendicitis in our department since its introduction 10 years ago. We report our experience with this technique and compare its outcome to open appendectomy (OA). The records of all children who underwent appendectomy at our institution over a period of 8 years were analyzed retrospectively. Patient baseline data, markers of inflammation, operative time, length of hospital stay, complication rate according to the classification of Clavien-Dindo, and histologic grading were assessed to compare the 2 surgical techniques (SPA and OA). The chi square test, the Student's t test and the Wilcoxon-Mann-Whitney test were used to analyze the data and the comparisons of the mean values. A P value < 0.05 was considered significant. Overall, 975 patients were included in the study. A total of 555 children had undergone SPA and 420 had been treated by OA. Median operative time of SPA was longer than that of OA (60.8 min vs 57.4 min; P < 0.05). Length of hospital stay after SPA was shorter than after OA (4.4 days and 5.9 days, respectively; P < 0.001). The overall complication rate was lower for SPA than that for OA (4.0% vs 5.7%), but the difference of complications for SPA and OA was not statistically significant (P < 0.22). SPA was successfully performed in 85.9% of children. In 53.8% of patients with perforated appendicitis, no conversion was required. In the group of children with perforated appendicitis, the complication rate of ~20% was independent of the surgical technique applied. With respect to operative time, length of hospital stay, and postoperative complication rate, SPA is not inferior to OA. SPA is safe and efficient, even in the management of perforated appendicitis. PMID- 26683963 TI - Associations Between Elastography Findings and Clinicopathological Factors in Breast Cancer. AB - This study aimed to explore the clinical significance of breast tumor tissue stiffness based on ultrasound elastographic evaluation in clinical breast cancer. Tumor tissue stiffness is mainly regulated by interactions among tumor cells, stromal cells, and extracellular matrix and was recently regarded as a representative feature of tumor microenvironment. Basic research has already revealed that the tumor stiffness can lead to tumor progression; however, little is known about its clinical significance because thus far, no useful modality is available in the clinical setting. We investigated the tumor stiffness by strain elastography in 503 consecutive patients with invasive breast cancer. Correlations between stiffness and clinicopathological factors, including tumor size, lymph node involvement, tumor subtypes, and stromal-related genes' expressions in primary breast tumor, were statistically examined. We identified that clinical tumor stiffness significantly correlated with lymph node involvement and invasive tumor size but not with hormonal receptor expressions, human epidermal growth factor receptor type 2 status, and ki67 labeling index by analyses of both categorical and continuous variables of stiffness. On multivariate analyses, axillary lymph node metastasis was an independent factor that influenced the stiffness of primary breast tumor. In the gene expression analyses, relatively hard tumors had a significantly high gene expression of lysyl oxidase compared with soft tumors. Our study showed a close relationship between primary tumor stiffness by elastographic evaluation and lymph node involvement in clinical breast cancer. Further investigations on tumor-related tissue stiffness are required. PMID- 26683964 TI - Small Cell Lung Cancer Accompanied by Tonsillar Metastasis and Anti-Hu Antibody Associated Paraneoplastic Neuropathy: A Rare Case Report With Long-Term Survival. AB - Tonsillar metastatic small cell lung cancer (SCLC) is rare, while anti-Hu antibodies are frequently found in SCLC. A 66-year-old man was admitted to our hospital with painful dysesthesia and muscle weakness in the distal extremities for over 1 year, progressive dysphagia for over 1 month, and severe cough and dyspnea for over 1 week. He was diagnosed with SCLC accompanied by tonsillar metastasis and anti-Hu antibody-associated paraneoplastic sensory neuropathy (PSN). The patient tolerated 6 cycles of sequential chemoradiotherapy and gradually recovered. The patient's disease remained in remission 2 years after the diagnosis with a remarkable reduction of tumor burden and a persisting high titer of anti-Hu antibodies. To our knowledge, this is the first case of tonsillar metastatic SCLC accompanied by anti-Hu antibody-associated PSN, whereby the anticancer immune response was presumed to play a vital role in disease control. Unilateral tonsillar metastasis of SCLC accompanied by anti-Hu antibody associated PSN can occur and in certain circumstances, may have a favorable prognosis. PMID- 26683965 TI - Clinical Features and Outcomes in Patients With Membranous Nephropathy and Crescent Formation. AB - Cases of membranous nephropathy (MN) with crescent formation, in the absence of lupus, hepatitis B virus infection, anti-glomerular basement membrane (GBM) nephritis, or antineutrophil cytoplasmic antibody (ANCA), are on record. Clinical presentation and treatment outcomes in these patients are unclear. All patients with biopsy-proven MN diagnosed between years 2008 and 2014 and followed up were enrolled retrospectively. Patients with ANCA, anti-GBM antibodies, lupus, hepatitis B virus infection, or malignance were excluded. Clinical features and outcomes were compared between MN patients with and without crescent. Out of 401 consecutive patients with idiopathic MN, 28 (6.9%) showed crescent formation in 4.9% (2.2%-16.7%) of glomeruli. Mean age of these patients was 50.1 +/- 11.1 years, and they presented with heavy proteinuria (6.5 +/- 4.8 g/24 h) and hematuria; 21.4% of these patients had declined estimated glomerular filtration rate (<60 mL/min/1.73 m2) on biopsy. Anti-phospholipase A2 receptor antibody was detectable in 79.7% of these patients. These clinical features were comparable to the MN patients without crescent (P > 0.05). Twelve (42.9%) patients received steroids plus immunosuppressive therapy similar to that in patients without crescent (41.3%). Fewer patients with crescents achieved remission (67.9% vs 86.7%, P = 0.029). Crescent formation was a risk factor for no response to the treatments (odds ratio [OR] = 3.1, P = 0.033). Higher percentage of crescents predicted more risk for no remission (OR = 1.2, P = 0.038). Patients with crescents presented more frequencies of abnormal serum creatinine during follow-up (10.7% vs 1.3%, P = 0.031). Crescent formation was also a risk factor for worse renal outcome (relative risk = 10.2, P = 0.046). MN patients with crescents showed unfavorable therapeutic response and tended to have worse renal outcomes. More aggressive treatments and renal protection might be considered to improve the outcomes. PMID- 26683966 TI - Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study. AB - Despite exhaustive efforts to detect early-stage ovarian cancers, greater than two-thirds of patients are diagnosed at an advanced stage. Although diaphragmatic metastasis is not rare in advanced ovarian cancer patients and often precludes optimal cytoreductive surgery, little is known about the mechanisms and predictive factors of metastasis to the diaphragm. Thus, as an initial step toward investigating such factors, the present study was conducted to characterize the pathological status of ovarian cancer patients who underwent debulking surgery in combination with diaphragmatic surgery. This is a retrospective and cross-sectional study of patients who underwent debulking surgery in combination with diaphragmatic surgery at our institution between January 2005 and July 2015. Clinicopathological data were reviewed by board certified gynecologists, pathologists, and cytopathologists. The rates of various pathological findings were investigated and compared by Fisher exact test between 2 groups: 1 group that was pathologically positive for diaphragmatic metastasis (group A) and another group that was pathologically negative for diaphragmatic metastasis (group B). Forty-six patients were included: 41 patients pathologically positive and 5 pathologically negative for diaphragmatic metastasis. The rates of metastasis to the lymph node (95.8% vs 20%, P = 0.001) and metastasis to the peritoneum except for the diaphragm (97.6% vs 60.0%, P = 0.028) were significantly increased in group A compared with group B. However, no significant differences between the 2 groups were found for rates of histological subtypes (high-grade serous or non-high-grade serous), the presence of ascites, the presence of malignant ascites, exposure of cancer cells on the ovarian surface, blood vascular invasion in the primary lesion, and lymphovascular invasion in the primary lesion. Our study demonstrated that metastasis to the lymph node and nondiaphragmatic metastasis to the peritoneum are significantly associated with metastasis to the diaphragmatic peritoneum, indicating that these factors may be pathological predictors of diaphragmatic metastasis in patients with ovarian cancer. However, as the data available are not sufficient to demonstrate the predictive power of these factors, a further comprehensive, large scale study should be performed. PMID- 26683967 TI - Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds: Evidence for Autoinflammation. AB - Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1beta, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. PMID- 26683968 TI - Risk of Early Mortality in Patients With Newly Diagnosed Multiple Myeloma. AB - The overall survival of patients with multiple myeloma (MM) has been improved greatly over the last 2 decades with the broader use of novel drugs and autologous tandem transplantation. However, more than one tenth of myeloma patients still die shortly after diagnosis. We therefore aim to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with MM. We included in this study 451 consecutive patients with MM, newly diagnosed at an Asian tertiary medical center between January 1, 2002 and April 30, 2015. A total of 57 subjects who experienced early mortality were identified. Risk factors for early mortality in myeloma patients were collected and analyzed. Early mortality occurred in 57 (12.6%) of the myeloma patients. In the multivariate analysis, being male (adjusted OR 2.93, 95% CI 1.17-7.31), serum albumin < 3.5 g/dL (adjusted OR 2.71, 95% CI 1.09-6.74), primary plasma cell leukemia (adjusted OR 17.61, 95% CI 1.01-306.05), serum albumin (adjusted OR 2.70, 95% CI 1.15-6.38), corrected serum calcium >= 12 mg/dL (adjusted OR 2.94, 95% CI 1.21-7.14), and LDH >= 250 U/L (adjusted OR 3.07, 95% CI 1.50-6.27) were identified as independent risk factors of early mortality. Pneumonia with other infections contributed most to early mortality (n = 36, 65%), followed by renal failure and cardiac failure. The early mortality rate is high (12.6%) in patients with MM. Patients who are male and those with primary plasma cell leukemia, low serum albumin, high-corrected serum calcium, or LDH are at risk of early mortality. Nearly two thirds of the myeloma patients who experienced early mortality in our study (37 of 57, 65%) died of infection. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection, and treatment of infections. PMID- 26683969 TI - Middle Cerebral Artery Calcification: Association With Ischemic Stroke. AB - Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93 14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID- 26683971 TI - Pattern of Venous Thromboembolism Occurrence in Gynecologic Malignancy: Incidence, Timing, and Distribution a 10-Year Retrospective Single-institutional Study. AB - The aim of this single-institutional 10-year retrospective study was to investigate the clinical pattern (incidence, type, timing, and location) of venous thromboembolism (VTE) in Chinese patients with gynecologic cancer. Cases were identified by searching institutional Electronic Discharge Database. A comprehensive review of medical documentation was then performed to collect relevant data. The detection of VTE was symptom-triggered. A total of 155 VTE events were identified out of 7562 cases over the past 10-year period in our hospital. The incidence of clinically significant VTE was 2.0% in gynecologic malignancy, with vulvar cancer (3.7%) and ovarian cancer (2.5%) being the high risk types (P = 0.01, Chi-square test). Perioperative period (35.1%) and preoperation (29.1%) were the 2 incidence peaks. Seventeen cases of pulmonary embolism (PE) occurred prior to surgery. Ovarian cancer patients were more likely to present preoperative PE compared to other site of cancer (76.4%; P = 0.01, Chi square test). More preoperative VTE cases were complicated by PE than those in the perioperative period (39.5% vs 17.3%, P = 0.02, Chi-square test). Bilateral lower extremity deep vein thrombosis (DVT) accounted for 32.6% and there existed a preponderance of left-sided DVT (47.5% vs 17.0%, ratio 2.79:1). Femoral vein (36.6%) was the most common location for DVT. About 2.0% of the Chinese patients with gynecologic carcinoma developed clinical VTE, mostly during perioperative period and the time of diagnosis. The true incidence might have been under estimated due to several reasons. The need for increased patient education and awareness of VTE is of importance. PMID- 26683970 TI - Impact of Modifiable Cardiovascular Risk Factors on Mortality After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of 100 Studies. AB - Modifiable cardiovascular risk factors such as obesity, hypertension, dyslipidemia, smoking, diabetes mellitus, and metabolic syndrome can easily give rise to coronary heart disease (CHD). However, due to the existence of the so called "obesity paradox" and "smoking paradox," the impact of these modifiable cardiovascular risk factors on mortality after percutaneous coronary intervention (PCI) is still not clear. Therefore, in order to solve this issue, we aim to compare mortality between patients with low and high modifiable cardiovascular risk factors after PCI. Medline and EMBASE were searched for studies related to these modifiable cardiovascular risk factors. Reported outcome was all-cause mortality after PCI. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated, and the pooled analyses were performed with RevMan 5.3 software. A total of 100 studies consisting of 884,190 patients (330,068 and 514,122 with high and low cardiovascular risk factors respectively) have been included in this meta-analysis. Diabetes mellitus was associated with a significantly higher short and long-term mortality with RR 2.11; 95% CI: (1.91-2.33) and 1.85; 95% CI: (1.66 2.06), respectively, after PCI. A significantly higher long-term mortality in the hypertensive and metabolic syndrome patients with RR 1.45; 95% CI: (1.24-1.69) and RR 1.29; 95% CI: (1.11-1.51), respectively, has also been observed. However, an unexpectedly, significantly lower mortality risk was observed among the smokers and obese patients. Certain modifiable cardiovascular risk subgroups had a significantly higher impact on mortality after PCI. However, mortality among the obese patients and the smokers showed an unexpected paradox after coronary intervention. PMID- 26683972 TI - Oculomotor Paralysis, Postorbital Pain, and Hypopituitarism as First Presentations of Metastatic Gastric Cancer in the Pituitary Flourished by Internal Carotid Aneurysm: A Case Report. AB - Metastatic gastric cancer in the pituitary (MGCP) is rare. Few are known on the clinical and radiological characteristics of MGCP. To date, the coexistence of metastatic pituitary tumors and intracranial aneurysms has not been reported in literatures. We present a case of MGCP with internal carotid aneurysm in a 57 year-old woman, who presented with oculomotor paralysis, postorbital pain, and hypopituitarism as onset symptoms. The patient had a history of the surgical removal of gastric cancer. Magnetic resonance imaging and single-photon emission computed tomography revealed a recurrent sellar mass with intracranial and multiple bone metastases. The patient underwent subtotal removal of the tumor, followed by conformal radiotherapy and chemotherapy. Ten months after surgery, the patient died due to deterioration of her overall condition. We also reviewed and analyzed the clinical data, imaging features, and treatment methods of additional 4 cases with MGCP, which were reported in literatures. This study provides important clinical information for the diagnosis and treatment of MGCP. PMID- 26683973 TI - Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study. AB - Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk. PMID- 26683975 TI - Blood pressure response to exercise in young athletes aged 10 to 18 years. AB - The aim of the study was to determine arterial blood pressure response to exercise in young athletes. The study group comprised 711 young athletes (457 boys, 254 girls) aged 10 to 18 years (mean 13.41 +/- 3.12 years) who had been training for an average of 7.62 +/- 4.2 h per week for an average of 4.01 +/- 2.5 years. Participants with elevated arterial blood pressure above the 90th percentile at rest were excluded from investigation. A symptom-limited, multistage exercise test to exhaustion was performed using a Monark cycle ergometer. Arterial blood pressure was measured with an aneroid manometer in the third minute of each stage of the test. Mean systolic arterial blood pressure during peak exercise was significantly higher in boys than in girls: 183.21 +/- 27.97 mm Hg and 170.97 +/- 21.4 mm Hg, respectively (p = 0.03). Multivariate linear regression analysis showed that age and workload had significant effects on arterial blood pressure during the test. Systolic arterial blood pressure during the exercise can be described with the following equations: boys, SBPex (mm Hg) = -1.92 * age (years) + 0.55 * workload (W) + 120.84; girls, SBPex (mm Hg) = -0.88 * age (years) + 0.48 * workload (W) + 111.22. The study results describe reference values of arterial blood pressure during the exercise test. The presented equations and figures can help to assess whether the arterial blood pressure at each stage of the exercise test exceeds the normal range or not. PMID- 26683974 TI - Chronic Intracerebroventricular Infusion of Monocyte Chemoattractant Protein-1 Leads to a Persistent Increase in Sweetened Ethanol Consumption During Operant Self-Administration But Does Not Influence Sucrose Consumption in Long-Evans Rats. AB - BACKGROUND: Among the evidence implicating neuroimmune signaling in alcohol use disorders are increased levels of the chemokine monocyte chemoattractant protein 1 (MCP-1) in the brains of human alcoholics and animal models of alcohol abuse. However, it is not known whether neuroimmune signaling can directly increase ethanol (EtOH) consumption, and whether MCP-1 is involved in that mechanism. We designed experiments to determine whether MCP-1 signaling itself is sufficient to accelerate or increase EtOH consumption. Our hypothesis was that increasing MCP-1 signaling by directly infusing it into the brain would increase operant EtOH self administration. METHODS: We implanted osmotic minipumps to chronically infuse either one of several doses of MCP-1 or vehicle into the cerebral ventricles (intracerebroventricular) of Long-Evans rats and then tested them in the operant self-administration of a sweetened EtOH solution for 8 weeks. RESULTS: There was a significant interaction between dose of MCP-1 and sweetened EtOH consumed across the first 4 weeks (while pumps were flowing) and across the 8-week experiment. Animals receiving the highest dose of MCP-1 (2 MUg/d) were the highest consumers of EtOH during weeks 3 through 8. MCP-1 did not influence the acquisition of self-administration (measured across the first 5 days), the motivation to consume EtOH (time to lever press or progressive ratio), withdrawal induced anxiety, or the consumption of sucrose alone. CONCLUSIONS: We provide novel evidence that neuroimmune signaling can directly increase chronic operant EtOH self-administration, and that this increase persists beyond the administration of the cytokine. These data suggest that EtOH-induced increases in MCP-1, or increases in MCP-1 due to various other neuroimmune mechanisms, may further promote EtOH consumption. Continued research into this mechanism, particularly using models of alcohol dependence, will help determine whether targeting MCP-1 signaling has therapeutic potential in the treatment of alcohol use disorders. PMID- 26683976 TI - One-Pot, High-Yielding, Oxidative Cyclodehydrogenation Route for N-Doped Nanographene Synthesis. AB - An intramolecular oxidative cyclodehydrogenation via a one-pot process is described, which induces selective C-C bond formation and bromine functionalization. The application of this new route gives rise to a novel family of partially fused, selectively brominated N-doped pyrimidine graphenes. PMID- 26683977 TI - Knee Arthrodesis in Persistently Infected Total Knee Arthroplasty. AB - The reported incidence of infection in total knee arthroplasty (TKA) varies from 0.5 to 15%. The most common indication for knee arthrodesis is persistent infection after repeated staged knee replacement. The purpose of this study is to investigate the success of fusion with monoplanar fixators and eradication rates of infection, and to evaluate the satisfaction of patients who underwent a last resort TKA due to infection.This is a retrospective review of infected knee arthroplasties that were treated with knee arthrodesis using unilateral external fixators at a single institution from 1999 through 2012. The patients' charts were analyzed for demographics, types of external fixators used, infection parameters, external fixator indexes, complications, positions of fusion, and leg length discrepancies (LLDs). Patients were called back to return for additional follow-up. A self-administered general health status questionnaire (SF-36) was assessed to evaluate life quality.There were 14 women and 3 men with an average age of 67 +/- 16.6 years. Antibiotic-loaded acrylic cements were used as a spacer for an average of 3.4 +/- 1.2 months in all patients. Monoplanar type of external fixator was used in all 17 patients. Fusions were achieved in all but one patient. The mean duration of fusion was 6.8 +/- 2.2 months and external fixator duration was 7.6 +/- 2.4 months. Average LLD was 2.9 +/- 1.7 cm. The mean coronal alignment of fusion was 6.8 degrees (+/- 3.3 degrees, range 4-15 degrees) valgus and mean flexion was 11.3 degrees (+/- 6.5 degrees, range 3-30 degrees). Compared with the healthy controls, the SF-36 scores were significantly lower in patients with knee arthrodesis (physical component score [PCS]-arthrodesis: 39.3 vs. PCS- healthy controls: 47.9, p < 0.05; mental component score [MCS]-arthrodesis: 38.6 versus MCS-healthy controls: 47.7, p < 0.05).Use of monoplanar fixators for arthrodesis in infected TKA can achieve high fusion rates with the control of infection. If fusion can be achieved, the patient satisfaction is low with acceptable pain relief and functionality. We observed that monoplanar external fixators increased patients' comfort levels compared with circular external fixators. Further studies are needed to compare different arthrodesis modalities in patients with infected TKA. PMID- 26683978 TI - Revisiting the Anterolateral Ligament of the Knee. AB - Recent research has suggested that the anterolateral ligament (ALL) of the knee may have an important role in preventing persistent rotatory instability following anterior cruciate ligament (ACL) reconstruction.For this review, we performed a thorough literature search and identified the significant steps in the improvement of our understanding. This has progressed from historical reports to accurate characterization of the attachments and dimensions of the ALL through anatomical and histological studies. Alongside this, biomechanical data have demonstrated the role of this structure throughout the range of movement of the knee. Furthermore, the appearance of the ALL on magnetic resonance imaging has been comprehensibly described and radiological markers have been defined as a basis for suggested reconstructive procedures using fluoroscopy.We present a comprehensive review of the evolution of our understanding about this structure. Key advances in our understanding of the dimensions and attachments will guide research into reconstructive options. Further work is needed to determine the biomechanical and clinical outcome of extra-articular reconstruction of the ALL alongside ACL reconstruction. PMID- 26683979 TI - Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. AB - There are few treatment options for symptomatic knee osteoarthritis (OA). Human amniotic suspension allografts (ASA) have anti-inflammatory and chondroregenerative potential and thus represent a promising treatment strategy. In anticipation of a large, placebo-controlled trial of intra-articular ASA for symptomatic knee OA, an open-label prospective feasibility study was performed. Six patients with Kellgren-Lawrence grades 3 and 4 tibiofemoral knee OA were administered a single intra-articular ASA injection containing cryopreserved particulated human amnion and amniotic fluid cells. Patients were followed for 12 months after treatment. No significant injection reactions were noted. Compared with baseline there were (1) no significant effect of the ASA injection on blood cell counts, lymphocyte subsets, or inflammatory markers and (2) a small, but statistically significant increase in serum IgG and IgE levels. Patient-reported outcomes including International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, and Single Assessment Numeric Evaluation scores were collected throughout the study and evaluated for up to 12 months. Overall, this study demonstrates the feasibility of a single intra-articular injection of ASA for the treatment of knee OA and provides the foundation for a large placebo controlled trial of intra-articular ASA for symptomatic knee OA. PMID- 26683980 TI - Nonpharmacologic Pain Management and Muscle Strengthening following Total Knee Arthroplasty. AB - Despite technological advances in total knee arthroplasty (TKA), management of postoperative muscle weakness and pain continue to pose challenges for both patients and health care providers. Nonpharmacologic therapies, such as neuromodulation in the form of neuromuscular electrical stimulation (NMES) and transcutaneous electrical nerve stimulation (TENS), and other modalities, such as cryotherapy and prehabilitation, have been highlighted as possible adjuncts to standard-of-care pharmacologic management to treat postoperative pain and muscle weakness. The aim of this review was to discuss existing evidence for neuromodulation in the treatment of pain and muscular weakness following TKA, and to shed light on other noninvasive and potential future modalities. Our review of the literature demonstrated that NMES, prehabilitation, and some specialized exercises are beneficial for postoperative muscle weakness, and TENS, cooling therapies, and compression may help to alleviate post-TKA pain. However, there are no clear guidelines for the use of these modalities. Further studies should be aimed at developing guidelines or delineating indications for neuromodulation and other nonpharmacologic therapies in the management of post-TKA pain and muscle weakness. PMID- 26683981 TI - Treatment of Peroneal Nerve Injuries in the Multiligament Injured/Dislocated Knee. AB - Tibiofemoral knee dislocations are typically a consequence of high-energy mechanisms, causing significant damage to the soft tissue and osseous structures of the knee. Concomitant neurovascular injuries such as popliteal artery and peroneal nerve injuries are also common and can have significant long-term consequences. The mechanism typically involves a traction injury to the peroneal nerve subsequent to an extreme varus moment applied to the knee. Complete nerve injuries typically hold a worse prognosis than incomplete palsies. Rates of functional recovery in the setting of a complete palsy following a knee dislocation event have been dismal. A period of observation and nonoperative treatment is initially performed, utilizing orthotic devices to assist with lower extremity deficits. Surgical treatment options include neurolysis, nerve grafting, tendon transfer, arthrodesis, and direct motor nerve transfers. Motor nerve transfers continue to be explored with initial reports showing promising results. PMID- 26683982 TI - The haematological features and transfusion management of women who required massive transfusion for major obstetric haemorrhage in the UK: a population based study. AB - Understanding the coagulopathy of major-obstetric-haemorrhage (MOH) that leads to massive-transfusion (MT) is fundamental to improving outcomes. This study reports on the haematological features and transfusion management of women experiencing MT [defined as transfusion of >=8 units of red blood cells (RBC) within 24 h of delivery]. One hundred and eighty-one cases [median (interquartile range; IQR) age 33 years (29-36)] were identified from all UK hospitals, using the UK Obstetric Surveillance System between July 2012 and June 2013. The median (IQR) estimated blood loss was 6 l (4.5-8). At presentation, the median platelet count was lowest for placenta accreta, compared with other causes, while the median prothrombin time and fibrinogen were <1.5 * mean normal and <3 g/l, respectively for all aetiologies. Median platelet count and fibrinogen fell to <75 * 10(9) /l and <2 g/l, respectively for all causes during bleeding, except for trauma. The median (IQR) units of RBC, fresh-frozen-plasma (FFP) and cryoprecipitate transfused were 10 (8-14), 6 (4-8) and 2 (2-4), respectively. The median time from the onset of bleeding to delivery of the first RBC unit was significantly shorter for women who delivered via elective caesarean section, compared with others. The coagulopathy of MT during MOH differs significantly depending on its cause, suggesting that more targeted transfusion strategies are required. PMID- 26683983 TI - Sexual Dysfunction Problems in Female College Students: Sexual Victimization, Substance Use, and Personality Factors. AB - Little empirical information is available on sexual dysfunction (SD) among college women even though college years represent a critical period in the development of sexuality. The current study aimed to identify factors associated with the presence, number, and type of SD problems among 547 female college students in the United States. Racial minority status, problematic drinking behaviors, and past sexual victimization were positively related to the presence of SD problems, whereas hormonal contraceptive use and past sexual victimization were associated with a greater number of SD problems. These findings highlight the importance of assessment, treatment, and prevention of sexual health issues on college campuses. PMID- 26683985 TI - Preexisting Chronic Health Conditions and Health Insurance Status Associated With Vaccine Receipt Among Adolescents. AB - PURPOSE: Four vaccines are routinely recommended for adolescents: tetanus, diphtheria, and acellular pertussis (Tdap); human papillomavirus (HPV); meningococcal-conjugate (MCV4); and a yearly seasonal influenza vaccine. Vaccination promotion and outreach approaches may need to be tailored to certain populations, such as those with chronic health conditions or without health insurance. METHODS: In a controlled trial among middle and high school students in Georgia, 11 schools were randomized to one of three arms: no intervention, parent education brochure, or parent education brochure plus a student curriculum on the four recommended vaccines. Parents in all arms were surveyed regarding their adolescent's vaccine receipt, chronic health conditions, and health insurance status. RESULTS: Of the 686 parents, most (91%) reported their adolescent had received at least one of the four vaccines: Tdap (82%), MCV4 (59%), current influenza vaccine (53%) and HPV (48%). Twenty-three percent of parents reported that their adolescent had asthma. Most parents reported that their adolescent's insurance was Medicaid (60%) or private insurance (34%), and 6% reported no insurance. More adolescents with a chronic health condition received any adolescent vaccine than adolescents without a chronic health condition (p < .0001). Among those with no insurance, fewer had received any adolescent vaccine than those with Medicaid or private insurance (p < .0001). CONCLUSIONS: The federal Vaccines for Children program offers recommended vaccines free to eligible children (including those without health insurance). Our findings suggest that parents may not be aware of this program or eligibility for it, thus revealing a need for education or other fixes. PMID- 26683986 TI - Effect of Lactotripeptides (Isoleucine-Proline-Proline/Valine-Proline-Proline) on Blood Pressure and Arterial Stiffness Changes in Subjects with Suboptimal Blood Pressure Control and Metabolic Syndrome: A Double-Blind, Randomized, Crossover Clinical Trial. AB - BACKGROUND: Lactotripeptides (LTPs) have a mild antihypertensive effect in hypertensive subjects. The main aim of our clinical trial was to test if LTPs could have some influence on blood pressure (BP) and related hemodynamic parameters in a sample of outpatients affected by metabolic syndrome. METHODS: A randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in a group of 40 nonsmoking volunteers with metabolic syndrome. The treatment periods were 4 weeks long and were separated by a 4-week washout period. The dietary supplementation was made by daily administration of LTPs from casein, 10.2 mg/day, and compared with placebo. RESULTS: During the LTP treatment, patients experienced a significant mean decrease in systolic BP (SBP; 3.4 +/- 4.4 mmHg, P = 0.041), diastolic BP (DBP; -3.1 +/- 3.2 mmHg, P = 0.049), and pulse wave velocity (PWV; -0.7 +/- 0.3 m/sec, P = 0.001). After LTP treatment, delta SBP, DBP, and PP were all significantly improved (P < 0.01 for all) compared with placebo. PWV also improved significantly after LTP treatment with respect to the end of the treatment with placebo (-0.8 +/- 0.4 vs. -0.1 +/- 0.3 m/sec, P = 0.009). The square root of the ratio of peak:baseline pulse volume during hyperemia (?V2/V1) improved after LTP treatment only (1.2 +/- 0.4 vs. 1.4 +/- 0.5, P = 0.04). Through the evaluation of the hemodynamic parameters that were measured by the 24-hr ambulatory monitoring, we observed that SBP, MBP, and the percentage of time with SBP over the normal were significantly reduced only after the LTP treatment (P < 0.05). These parameters were also significantly improved when compared with the ones measured after the placebo treatment (P < 0.05). CONCLUSION: In our trial, during LTP treatment, patients affected by metabolic syndrome experienced a mild but significant improvement in office and 24-hr BP, PWV, and endothelial function compared with placebo treatment. PMID- 26683984 TI - In Search of Teen Dating Violence Typologies. AB - PURPOSE: The goal of the present research was to identify distinct latent classes of adolescents that commit teen dating violence (TDV) and assess differences on demographic, behavioral, and attitudinal correlates. METHODS: Boys and girls (N = 1,149; Mage = 14.3; Grades 6-12) with a history of violence exposure completed surveys assessing six indices of TDV in the preceding 3 months. Indices of TDV included controlling behaviors, psychological TDV, physical TDV, sexual TDV, fear/intimidation, and injury. In addition, adolescents provided demographic and dating history information and completed surveys assessing attitudes condoning violence, relationship skills and knowledge, and reactive/proactive aggression. RESULTS: Latent class analysis indicated a three-class solution wherein the largest class of students was nonviolent on all indices ("nonaggressors") and the smallest class of students demonstrated high probability of nearly all indices of TDV ("multiform aggressors"). In addition, a third class of "emotional aggressors" existed for which there was a high probability of controlling and psychological TDV but low likelihood of any other form of TDV. Multiform aggressors were differentiated from emotional and nonaggressors on the use of self-defense in dating relationships, attitudes condoning violence, and proactive aggression. Emotional aggressors were distinguished from nonaggressors on nearly all measured covariates. CONCLUSIONS: Evidence indicates that different subgroups of adolescents engaging in TDV exist. In particular, a small group of youth engaging in multiple forms of TDV can be distinguished from a larger group of youth that commit acts of TDV restricted to emotional aggression (i.e., controlling and psychological) and most youth that do not engage in TDV. PMID- 26683987 TI - A highly sensitive and selective LC-MS/MS method to quantify asunaprevir, an HCV NS3 protease inhibitor, in human plasma in support of pharmacokinetic studies. AB - Asunaprevir (BMS-650032) is a selective hepatitis C virus (HCV) NS3 protease inhibitor with potent activity against HCV genotypes 1, 4, 5 and 6. It has been developed in conjunction with direct-acting antiviral agents, in interferon- and ribavirin-free regimen, to improve existing therapies for HCV infection. To support the pharmacokinetic analyses in asunaprevir clinical studies, we have developed and validated a highly sensitive and robust LC-MS/MS method to quantify asunaprevir in human EDTA plasma with an LLOQ of 0.05ng/mL, which was a 20-fold sensitivity improvement over a previously reported assay for asunaprevir. A deuterated labeled [D9]-asunaprevir was used as the internal standard (IS). The analyte and the IS were extracted using a semi-automated liquid-liquid extraction (LLE) at pH 7 with methyl-t-butyl ether (MTBE) in a 96-well plate containing 10MUL of 10% CHAPS as the surfactant to prevent non-specific binding issue. Chromatographic separation was achieved on a Genesis C8 column (2.1*50mm, 4MUm) with a gradient elution using 0.1% formic acid in water as mobile phase A and a mixture of methanol: acetone: formic acid (95:5:0.1; v/v/v) as the mobile phase B. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 748->648 for asunaprevir and m/z 757 >649 for [D9]-asunaprevir,and a collision energy of 30 electron Volts (eV). The assay was validated over a standard curve range from 0.05 to 50ng/mL for asunaprevir in human plasma. The intra- and inter assay precisions were within 7.1% CV, and the % deviation was within 5.5% of their nominal concentrations. This assay has been successfully applied to multiple clinical studies with excellent assay ruggedness and reproducibility. PMID- 26683988 TI - Pre-clinical investigation of the modulation of quetiapine plasma pharmacokinetics and tissues biodistribution by lipid-core nanocapsules. AB - This study aims to investigate the changes in plasma pharmacokinetics and liver and brain distribution of quetiapine (QTP) due to its encapsulation into a polymeric nanocarrier. For this reason a bioanalytical method was developed and validated in order to quantify QTP in plasma, liver and brain tissue samples. The method was linear over the concentration range of 0.025-3.0MUg.mL (r(2)>0.98), accurate, precise (R.S.D<+/-15%) and the recoveries, stability and validation parameters are within the acceptable limits determined by international guidelines. Plasma pharmacokinetics, cerebral and hepatic distribution of the drug were carried out after intravenous administration of 5mgkg(-1) of nanoencapsulated (QLNC) or free-QTP to male Wistar rats. Increasing half-life was observed for QLNC in relation to free-QTP due to o significant decrease in total clearance. QTP volume of distribution was not altered due to encapsulation. An increase in QTP liver exposure was observed after nanoencapsulation probably due to a reduction in drug metabolization process. PMID- 26683989 TI - Nephrotoxicity evaluation of a new cembrane diterpene from Euphorbiae pekinensis Radix with HEK 293T cells and the toxicokinetics study in rats using a sensitive and reliable UFLC-MS/MS. AB - (-)-(1S)-15-Hydroxy-18-carboxycembrene, the first cembrane-type diterpenoid found in the family Euphorbiaceae, isolated from Euphorbiae pekinensis Radix, was identified to be nephrotoxic using HEK 293T cells. Tests on cell morphology, cell viability and biochemical markers about oxidation stress were carried out using inverted microscope, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and commercial kits respectively, which proved the diterpene time- and dose-dependently decreased cells proliferation. Besides, a sensitive and robust UFLC-MS/MS method was developed and fully validated to investigate the in vivo behavior in rats of the diterpene after oral administration of Euphorbiae pekinensis Radix extracts at a dosage of 9g/kg. The method showed a good linearity in tested range (3-1500ng/mL) with acceptable accuracy and precision. The recovery of the diterpene was more than 85% and the matrix effect was within +/-20%. The toxicokinetics parameters indicate the diterpene reached Cmax quickly and slowly eliminate. The study proved the newly found diterpene was one of the nephrotoxic substances of Euphorbiae pekinensis Radix and revealed its toxicokinetics behavior. PMID- 26683990 TI - Metabolism of dictamnine in liver microsomes from mouse, rat, dog, monkey, and human. AB - Dictamnine, a furoquinoline alkaloid isolated from the root bark of Dictamnus dasycarpus Turcz. (Rutaceae), is reported to have a wide range of pharmacological activities. In this study, the in vitro metabolic profiles of dictamnine in mouse, rat, dog, monkey, and human liver microsomes were investigated and compared. Dictamnine was incubated with liver microsomes in the presence of an NADPH-regenerating system, resulting in the formation of eight metabolites (M1 M8). M1 is an O-desmethyl metabolite. M5 and M6 are formed by a mono hydroxylation of the benzene ring of dictamnine. M8 was tentatively identified as an N-oxide metabolite. The predominant metabolic pathway of dictamnine occurs through the epoxidation of the 2,3-olefinic to yield a 2,3-epoxide metabolite (M7), followed by the ring of the epoxide opening to give M4. Likewise, cleavage of the furan ring forms M2 and M3. Slight differences were observed in the in vitro metabolic profiles of dictamnine among the five species tested. A chemical inhibition study with a broad and five specific CYP450 inhibitors revealed that most of the dictamnine metabolites in liver microsomes are mediated by CYP450, with CYP3A4 as the predominant enzyme involved in the formation of M7, the major metabolite. These findings provide vital information to better understand the metabolic processes of dictamnine among various species. PMID- 26683991 TI - Inter- versus Intramolecular Structural Manipulation of a Dichromium(II) Pacman Complex through Pressure Variation. AB - The effect of pressure on the intranuclear M...M separation and intermolecular secondary interactions in the dinuclear chromium Pacman complex [Cr2(L)](C6H6) was evaluated because this compound contains both a short Cr...Cr separation and an exogenously bound molecule of benzene in the solid state. The electronic structure of [Cr2(L)] was determined by electron paramagnetic resonance spectroscopy, SQUID magnetometry, and density functional theory calculations and shows a diamagnetic ground state through antiferromagnetic exchange, with no evidence for a Cr-Cr bond. Analysis of the solid-state structures of [Cr2(L)](C6H6) at pressures varying from ambient to 3.0 GPa shows little deformation in the Cr...Cr separation, i.e., no Cr-Cr bond formation, but instead a significantly increased interaction between the exogenous arene and the chromium iminopyrrolide environment. It is therefore apparent from this analysis that [Cr2(L)] would be best exploited as a rigid chemical synthon, with pressure regulation being used to mediate the approach and secondary interactions of possible substrates. PMID- 26683992 TI - 2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy. AB - A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting. PMID- 26683993 TI - Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats. AB - Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN). The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat. PMID- 26683994 TI - Hemoglobin Constant Spring among Southeast Asian Populations: Haplotypic Heterogeneities and Phylogenetic Analysis. AB - BACKGROUND: Hemoglobin Constant Spring (Hb CS) is an abnormal Hb caused by a mutation at the termination codon of alpha2-globin gene found commonly among Southeast Asian and Chinese people. Association of Hb CS with alpha degrees thalassemia leads to a thalassemia intermedia syndrome commonly encountered in the region. We report chromosome background and addressed genetic origins of Hb CS observed in a large cohort of Hb CS among Southeast Asian populations. MATERIALS AND METHODS: A study was done on 102 Vietnamese (aged 15-49 year-old) and 40 Laotian (aged 18-39 year-old) subjects with Hb CS and results compared with 120 Hb CS genes in Thailand. Hematological parameters were recorded and Hb analysis was performed using capillary electrophoresis. Hb CS mutation and thalassemia genotypes were defined by DNA analysis. Six DNA polymorphisms within alpha-globin gene cluster including 5'Xba I, Bgl I, Inter-zeta HVR, AccI, RsaI and alphaPstI 3', were determined using PCR-RFLP assay. RESULTS: Nine different genotypes of Hb CS were observed. In contrast to the Thai Hb CS alleles which are mostly linked to haplotype (+-S + + -), most of the Vietnamese and the Laotian Hb CS genes were associated with haplotype (+-M + + -), both of which are different from that of the European Hb CS. CONCLUSIONS: Hb CS is commonly found in combination with other thalassemias among Southeast Asian populations. Accurate genotyping of the cases requires both hematologic and DNA analyses. At least two independent origins are associated with the Hb CS gene which could indirectly explain the high prevalence of this Hb variant in the region. PMID- 26683995 TI - Infective endocarditis and cancer in the elderly. AB - Little is known about the magnitude of the association between infective endocarditis and cancer, and about the natural history of cancer patients with concomitant diagnosis of infective endocarditis. We used the SEER-Medicare linked database to identify individuals aged 65 years or more diagnosed with colorectal, lung, breast, or prostate cancer, and without any cancer diagnosis (5% random Medicare sample from SEER areas) between 1992 and 2009. We identified infective endocarditis from the ICD-9 diagnosis of each admission recorded in the Medpar file and its incidence rate 90 days around cancer diagnosis. We also estimated the overall survival and CRC-specific survival after a concomitant diagnosis of infective endocarditis. The peri-diagnostic incidence of infective endocarditis was 19.8 cases per 100,000 person-months for CRC, 5.7 cases per 100,000 person months for lung cancer, 1.9 cases per 100,000 person-months for breast cancer, 4.1 cases per 100,000 person-months for prostate cancer and 2.4 cases per 100,000 person-months for individuals without cancer. Two-year overall survival was 46.4% (95% CI 39.5, 54.5%) for stage I-III CRC patients with concomitant endocarditis and 73.1% (95 % CI 72.9, 73.3%) for those without it. In this elderly population, the incidence of infective endocarditis around CRC diagnosis was substantially higher than around the diagnosis of lung, breast and prostate cancers. A concomitant diagnosis of infective endocarditis in patients with CRC diagnosis is associated with shorter survival. PMID- 26683996 TI - Puromycin aminonucleoside increases podocyte permeability by modulating ZO-1 in an oxidative stress-dependent manner. AB - Puromycin aminonucleoside (PAN)-induced nephrosis is a widely studied animal model of human idiopathic nephrotic syndrome because PAN injection into rats results in increased glomerular permeability with the characteristic ultrastructural changes in podocytes similar to human nephrosis. To investigate the role of zonula occludens (ZO)-1 and oxidative stress on PAN-induced podocyte phenotypical changes and hyperpermeability in vitro, we cultured rat and mouse podocytes and treated with various concentrations of PAN. PAN treatment increased oxidative stress level of podocytes significantly with the induction of Nox4. In addition, PAN changed the ultrastructure of podocytes, such as shortening and fusion of microvilli, and the separation of intercellular gaps, which were improved by anti-oxidative vitamin C and Nox4 siRNA. PAN also disrupted the intercellular linear ZO-1 staining and induced inner cytoplasmic re-localization of ZO-1 protein, resulting in increased podocyte intercellular permeability. PAN reduced ZO-1 protein amount and mRNA expression in a dose-dependent manner, which means that PAN could also modulate ZO-1 protein transcriptionally. However, the decreased ZO-1 protein of podocytes by PAN was improved by Nox4 siRNA transfection. Furthermore, vitamin C mitigated the quantitative and distributional disturbances of ZO-1 protein caused by PAN. Our results demonstrate that the phenotypical changes of intercellular ZO-1 by oxidative stress via Nox4 likely contribute to the glomerular hyperpermeability caused by PAN. PMID- 26683997 TI - TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models. AB - Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4(+) T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4(+) T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4(+) T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-gamma and IL-17, and increased that of IL-10, as determined by ELISA and qRT PCR. In CD4(+) T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-gamma, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients. PMID- 26683998 TI - Documenting Pornography Use in America: A Comparative Analysis of Methodological Approaches. AB - Estimates of pornography use in the United States range widely. We explore the reasons for the variation in such estimates among U.S. adults using data from four different recent nationally representative samples-each of which asked a different type of question about pornography use. We attribute the notable variation in estimates to differences in question wording and answer options, and assert that a survey question asking respondents about their most recent use of pornography minimizes recall bias and is better poised to assess the overall prevalence of pornography in a population than is the more common approach of asking respondents about their historical general-use pattern. When we privileged the most-recent-use approach, survey data from 2014 reveal that 46% of men and 16% of women between the ages of 18 and 39 intentionally viewed pornography in a given week. These numbers are notably higher than most previous population estimates employing different types of questions. The results have ramifications for methods of surveying sensitive self-reported behaviors and for contextualizing scholars' claims as well as popular conversations about the reach and implications of pornography use in the United States. PMID- 26683999 TI - Silent Encoding of Chemical Post-Translational Modifications in Phage-Displayed Libraries. AB - In vitro selection of chemically modified peptide libraries presented on phage, while a powerful technology, is limited to one chemical post-translational modification (cPTM) per library. We use unique combinations of redundant codons to encode cPTMs with "silent barcodes" to trace multiple modifications within a mixed modified library. As a proof of concept, we produced phage-displayed peptide libraries Ser-[X]4-Gly-Gly-Gly, with Gly and Ser encoded using unique combinations of codons (TCA-[X]4-GGAGGAGGA, AGT-[X]4-GGTGGTGGT, etc., where [X]4 denotes a random NNK library). After separate chemical modification and pooling, mixed-modified libraries can be panned and deep-sequenced to identify the enriched peptide sequence and the accompanying cPTM simultaneously. We panned libraries bearing combinations of modifications (sulfonamide, biotin, mannose) against matched targets (carbonic anhydrase, streptavidin, concanavalin A) to identify desired ligands. Synthesis and validation of sequences identified by deep sequencing revealed that specific cPTMs are significantly enriched in panning against the specific targets. Panning on carbonic anhydrase yielded a potent ligand, sulfonamide-WIVP, with Kd = 6.7 +/- 2.1 nM, a 20-fold improvement compared with the control ligand sulfonamide-GGGG. Silent encoding of multiple cPTMs can be readily incorporated into other in vitro display technologies such as bacteriophage T7 or mRNA display. PMID- 26684000 TI - Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions. AB - Despite the partial disorder-to-order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non-specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C-terminal domain of the measles virus (MeV) nucleoprotein (NTAIL ) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N-terminal region of NTAIL remains conspicuously disordered, with alpha-helical folding taking place only within a short molecular recognition element. To study the effect of the N-terminal fuzzy region on NTAIL /XD binding, we generated N-terminal truncation variants of NTAIL , and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N-terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL /XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence-independent inhibitory effect of the fuzzy region. PMID- 26684002 TI - Stability enhancement of PbSe quantum dots via post-synthetic ammonium chloride treatment for a high-performance infrared photodetector. AB - Infrared (IR) emission lead selenide (PbSe) quantum dots (QDs) have gained considerable attention in the last decade due to their potential applications in optoelectronic devices. However, the comprehensive applications of PbSe QDs have not been realized yet due to their high susceptibility to oxidation in air. In this paper, we demonstrate the stability enhancement of PbSe colloidal QDs via a post-synthetic ammonium chloride treatment and its applications in a solution processed high-performance IR photodetector with a field-effect transistor (FET) configuration by reversely fabricating the PbSe active layer and polymethylmethacrylate (PMMA) dielectric layer. The responsivity and the specific detectivity of the FET-based photodetector Au(source, drain)/PbSe(52 nm)/PMMA(930 nm)/Au(gate) reached 64.17 mA W(-1) and 5.08 * 10(10) Jones, respectively, under 980 nm laser illumination with an intensity of 0.1 mW cm(-2). Therefore, it provides a promising way to make a high-sensitivity near-IR/mid-IR photodetector. PMID- 26684001 TI - Influence of Body Mass Index on the Prognostic Value of Tumor 18F-FDG Uptake in Stage I Non-Small Cell Lung Cancer. AB - BACKGROUND: The impact of host energy balance status on outcome of lung cancer has not been fully explored. It is also unknown if there is a potential modifying effect of body mass index (BMI) on tumor cell behavior in patients with early stage non-small cell lung cancer (NSCLC). We therefore investigated the interactive effects of tumor [18F]-fluorodeoxyglucose (FDG) avidity and BMI. METHODS: We investigated 1,197 patients with stage I NSCLC who underwent preoperative FDG positron emission tomography followed by curative resection. The primary outcome measure was disease-free survival (DFS). A multivariable Cox proportional hazards model was used to assess the potential independent effects of the prognostic variables. A stratified Cox regression analysis was also performed to assess the potential modifying effects of BMI on the relationship between tumor FDG uptake and patient survival. RESULTS: There were 145 tumor recurrences and 19 deaths during a median follow-up of 30 months. Tumor-related variables, including tumor size, maximum standardized uptake value (SUVmax), histologic cell type, differentiation, lymphovascular invasion, and visceral pleural invasion, did not differ significantly according to BMI status. In multivariable Cox regression analysis, overweight or obesity [hazard ratio (HR), 0.59; 95% CI, 0.43-0.81; P = 0.001] and tumor SUVmax (HR, 1.72; 95% CI, 1.43 2.07; P < 0.001) were significantly associated with DFS. There was a significant modifying effect of BMI (P for interaction < 0.001 in multivariable analysis). High tumor SUVmax was more strongly associated with worse DFS in normal weight patients (HR, 4.72; 95% CI, 2.77-8.06; P < 0.001) than in overweight or obese patients (HR, 2.61; 95% CI, 1.58-4.31; P < 0.001). CONCLUSIONS: Tumor FDG avidity is an independent predictor of DFS in patients with early-stage NSCLC and this prognostic value was strengthened in normal weight patients than in overweight or obese patients. These results suggest that the host-tumor interaction between host energy balance status and tumor glucose metabolism plays an important role in the outcome of early-stage NSCLC. PMID- 26684003 TI - Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean. AB - The soybean aphid (Aphis glycines Matsumura) is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of "metabolic hijacking" by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor. PMID- 26684004 TI - Kinetic response of wild and mutant core codon 70 strains of HCV genotype 1b to pegylated interferon-alpha and ribavirin therapy. AB - BACKGROUND: Amino acid (aa) 70 substitution (R70Q/H) in the core protein of hepatitis C virus (HCV) genotype 1b has been shown to be one of the key factors in determining resistance for pegylated interferon-alpha plus ribavirin combination therapy (PEG-IFNalpha/RBV). But the exact mechanisms remain unclear. The aim of this study was to investigate the dynamic response of wild and mutant core codon 70 strains to PEG-IFNalpha/RBV treatment. METHODS: One hundred twelve Chinese patients with chronic HCV 1b infection were enrolled and received a standard protocol of 48 weeks of PEG-IFNalpha/RBV therapy and 24 consecutive weeks of follow-up. Serial blood samples were obtained at pretreatment baseline, and again at weeks 2, 4, 8, 12, and 24 during therapy for the quantification of 70R and 70Q/H strains. Dynamic characteristics and association with early virological response (EVR), sustained virological response (SVR) and IL28B genotypes were analyzed. RESULTS: Of the 112 patients enrolled in this study, 93.8% (105/112) were infected with mixture of 70R and 70Q/H strains before treatment. The 70Q/H strain was dominant in 20.5% of patients. 42.9% of patients with dominant 70Q/H exhibited EVR versus 88.6% of patients with dominant 70R (P < 0.001). Furthermore, 35.0% of patients with dominant 70Q/H exhibited SVR versus 77.4% with dominant 70R (P < 0.001). However, regardless of the dominant strain, virological response types or the IL28B SNP genotypes, 70Q/H strains always exhibited the same response to treatment as the 70R strains and the percentage of HCV harboring the 70Q/H substitution did not change significantly during treatment. CONCLUSIONS: Although the ratio of 70Q/H to 70R is related to the virological response, 70Q/H strains always exhibited the same response as the 70R strains during PEG-IFNalpha/RBV treatment. Substitution of R70Q/H alone is not enough to lead to resistance to therapy. Positive selection for 70Q/H induced by IFNalpha was not observed. PMID- 26684007 TI - White-rot fungus Ganoderma sp.En3 had a strong ability to decolorize and tolerate the anthraquinone, indigo and triphenylmethane dye with high concentrations. AB - The ability of the white-rot fungus Ganoderma sp.En3 to decolorize different kinds of dyes widely applied in the textile and dyeing industry, including the anthraquinone dye Remazol Brilliant Blue R (RBBR), indigo dye indigo carmine and triphenylmethane dye methyl green, was evaluated in this study. Ganoderma sp.En3 had a strong capability of decolorizing high concentrations of RBBR, indigo carmine and methyl green. Obvious reduction of Chemical Oxygen Demand was observed after decolorization of different dyes. Ganoderma sp.En3 had a strong ability to tolerate RBBR, indigo carmine and methyl green with high concentrations. High concentrations of RBBR, indigo carmine and methyl green could also be efficiently decolorized by the crude enzyme of Ganoderma sp.En3. Different redox mediators such as syringaldehyde, acetosyringone and acetovanillone could enhance the decolorization capability for higher concentration of indigo carmine and methyl green. Different metal ions had little effect on the ability of the crude enzyme to decolorize indigo carmine and methyl green. Our study suggested that Ganoderma sp.En3 had a strong capability for decolorizing and tolerating high concentrations of different types of dyes such as RBBR, indigo carmine and methyl green. PMID- 26684006 TI - Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome. AB - BACKGROUND: Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro. METHODS: Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR. RESULTS: Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and splice site mutations were significantly lower than the levels in patients with missense mutations. A high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in three of his first degree relatives. No association was indicated between the FBN1 transcript level and specific phenotypic manifestations. CONCLUSIONS: Abnormal FBN1 transcripts were indicated in fibroblasts from patients with the splice site mutation c.4817-2delA and the missense mutation c.A4925G. While the mean FBN1 mRNA expression level in fibroblasts from patients with splice site and PTC mutations were lower than the mean level in patients with missense mutations and controls, inter-individual variability was high. The observation that high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in the family suggests that variable expression of the normal FBN1 allele may contribute to explain the variability in FBN1 mRNA level. PMID- 26684008 TI - A Facile Solid-Phase Route to Renewable Aromatic Chemicals from Biobased Furanics. AB - Renewable aromatics can be conveniently synthesized from furanics by introducing an intermediate hydrogenation step in the Diels-Alder (DA) aromatization route, to effectively block retro-DA activity. Aromatization of the hydrogenated DA adducts requires tandem catalysis, using a metal-based dehydrogenation catalyst and solid acid dehydration catalyst in toluene. Herein it is demonstrated that the hydrogenated DA adducts can instead be conveniently converted into renewable aromatics with up to 80% selectivity in a solid-phase reaction with shorter reaction times using only an acidic zeolite, that is, without solvent or dehydrogenation catalyst. Hydrogenated adducts from diene/dienophile combinations of (methylated) furans with maleic anhydride are efficiently converted into renewable aromatics with this new route. The zeolite H-Y was found to perform the best and can be easily reused after calcination. PMID- 26684009 TI - Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study. AB - Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV. PMID- 26684011 TI - The impact of self-monitoring in chronic illness on healthcare utilisation: a systematic review of reviews. AB - BACKGROUND: Self-management interventions have been found to reduce healthcare utilisation in people with long-term conditions, but further work is needed to identify which components of these interventions are most effective. Self monitoring is one such component and is associated with significant clinical benefits. The aim of this systematic review of reviews is to assess the impact of self-monitoring interventions on healthcare utilisation across a range of chronic illnesses. METHODS: An overview of published systematic reviews and meta analyses. Multiple databases were searched (MEDLINE, CINAHL, PsycINFO, EMBASE, AMED, EBM and HMIC) along with the reference lists of included reviews. A narrative synthesis was performed, accompanied by calculation of the Corrected Cover Area to understand the impact of overlapping primary research papers. RESULTS: A total of 17 systematic reviews and meta-analyses across three chronic conditions, heart failure, hypertension and chronic obstructive pulmonary disease, were included. Self-monitoring was associated with significant reductions in hospitalisation and re-admissions to hospital. CONCLUSIONS: Self monitoring has the potential to reduce the pressure placed on secondary care services, but this may lead to increase in services elsewhere in the system. Further work is needed to determine how these findings affect healthcare costs. PMID- 26684010 TI - Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice. AB - Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5MUM), resveratrol stimulated complex I activity, whereas at high dose (50 MUM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed. PMID- 26684012 TI - Molecular characterization of midgut microbiota of Aedes albopictus and Aedes aegypti from Arunachal Pradesh, India. AB - BACKGROUND: Microbiota inhabiting midguts of mosquitoes play a key role in the host - parasite interaction and enhance vectorial capacity of viral diseases like dengue and chikungunya fevers. Mosquito midgut is considered to be an important site for host-pathogen interaction and pathogen survival is thought to be an outcome of this interaction. In the present study we examined the bacterial community in the midgut of Aedes mosquitoes in Arunanchal Pradesh, India, a subtropical zone where dengue fever is reported to be emerging. METHOD: Larvae and pupa of Aedes mosquitoes were collected from a biodiversity hotspot, Bhalukpong, Arunachal Pradesh, India. 16S rRNA gene sequences were used for identification of isolated bacterial population from each species of mosquitoes. We used various diversity indices to assess the diversity and richness of the bacterial isolates in both mosquito species. RESULT: On the basis of 16S rRNA gene sequence analysis a total of 24 bacterial species from 13 genera were identified belonging to 10 families of four major phyla. Phylum Proteobacteria was dominant followed by Firmicutes, Bacteroidetes and Actinobacteria. The midgut bacteria belonging to the phylum Proteobacteria and Firmicutes were isolated from both Ae. albopictus and Ae. aegypti, whereas, bacteria belonging to phylum Bacteroidetes and Actinobacteria were isolated only from Ae. albopictus and Ae. aegypti respectively. Enterobacter cloacae was the dominant bacterial species in both Ae. albopictus (33.65%) and Ae. aegypti (56.45%). Bacillus aryabhattai (22.78%) was the second most common bacterial species in Ae. albopictus whereas, in Ae. aegypti the second most common bacterial species was Stenotrophomonas maltophilia (7.44%). CONCLUSION: The family Enterobacteriaceae of phylum Proteobacteria was dominant in both species of Aedes mosquitoes. To the best of our knowledge, this is the first attempt to study midgut microbiota from a biodiversity hotspot in Northeastern India. Some bacterial genera Enterobacter and Acinetobacter isolated in this study are known to play important roles in parasite-vector interaction. Information on midgut microflora may lead towards the development of novel, safe, and effective strategies to manipulate the vectorial capacity of mosquitoes. PMID- 26684014 TI - US government is funding fewer trials as number of industry sponsored trials grows. PMID- 26684015 TI - Analysis of surgery for incurable gastric cancer. AB - BACKGROUND: It is important to evaluate the curability of and avoid unnecessary exploratory surgery for gastric cancer preoperatively. However, no related research has been reported until now. The aim of this study was to evaluate the factors influencing surgery for incurable gastric cancer. METHODS: 310 cases of T3-4 gastric cancer patients were analyzed retrospectively, including 141 cases with radical surgery and 169 with surgery for incurable gastric cancer. The incurable factors were categorized as T status (unresectable T4 tumor), N status (unresectable lymph node), peritoneal metastasis, and distant metastasis. chi (2) test and logistic regression were performed to analyze the associations between curability, T status, N status, peritoneal metastasis, or distant metastasis and clinicopathological data. RESULTS: Esophageal involvement and T grade were associated with curability. Cardia involvement and Borrmann type were associated with T status. Esophageal involvement and T grade were associated with N status. Gastric body involvement, esophageal involvement, and T grade were associated with peritoneal metastasis. Gastric antrum involvement was associated with distant metastasis. CONCLUSIONS: The influencing factors of surgery for incurable gastric cancer should be analyzed preoperatively. Resectability should be evaluated according to these influencing factors combined with imaging analysis. PMID- 26684013 TI - EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair. AB - Replication fork stalling and collapse is a major source of genome instability leading to neoplastic transformation or cell death. Such stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR) or non-conservatively repaired using micro-homology mediated end joining (MMEJ). HR repair of stressed forks is initiated by 5' end resection near the fork junction, which permits 3' single strand invasion of a homologous template for fork restart. This 5' end resection also prevents classical non-homologous end-joining (cNHEJ), a competing pathway for DNA double-strand break (DSB) repair. Unopposed NHEJ can cause genome instability during replication stress by abnormally fusing free double strand ends that occur as unstable replication fork repair intermediates. We show here that the previously uncharacterized Exonuclease/Endonuclease/Phosphatase Domain-1 (EEPD1) protein is required for initiating repair and restart of stalled forks. EEPD1 is recruited to stalled forks, enhances 5' DNA end resection, and promotes restart of stalled forks. Interestingly, EEPD1 directs DSB repair away from cNHEJ, and also away from MMEJ, which requires limited end resection for initiation. EEPD1 is also required for proper ATR and CHK1 phosphorylation, and formation of gamma-H2AX, RAD51 and phospho-RPA32 foci. Consistent with a direct role in stalled replication fork cleavage, EEPD1 is a 5' overhang nuclease in an obligate complex with the end resection nuclease Exo1 and BLM. EEPD1 depletion causes nuclear and cytogenetic defects, which are made worse by replication stress. Depleting 53BP1, which slows cNHEJ, fully rescues the nuclear and cytogenetic abnormalities seen with EEPD1 depletion. These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ. PMID- 26684016 TI - Entry of equid herpesvirus 1 into CD172a+ monocytic cells. AB - Equid herpesvirus 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Cells from the myeloid lineage (CD172a+) are one of the main target cells of EHV-1 during primary infection. Recently, we showed that EHV-1 restricts and delays its replication in CD172a+ cells as part of an immune evasive strategy to disseminate to target organs. Here, we hypothesize that a low efficiency of EHV-1 binding to and entry in CD172a+ cells is responsible for this restriction. Thus, we characterized EHV-1 binding and entry into CD172a+ cells, and showed that EHV-1 only bound to 15-20 % of CD172a+ cells compared with 70 % of RK-13 control cells. Enzymic removal of heparan sulphate did not reduce EHV-1 infection, suggesting that EHV-1 does not use heparan sulphate to bind and enter CD172a+ cells. In contrast, we found that treatment of cells with neuraminidase (NA) reduced infection by 85-100 % compared with untreated cells, whilst NA treatment of virus had no effect on infection. This shows that sialic acid residues present on CD172a+ cells are essential in the initiation of EHV-1 infection. We found that alphaVbeta3 integrins are involved in the post-binding stage of CD172a+ cell infection. Using pharmacological inhibitors, we showed that EHV-1 does not enter CD172a+ cells via a clathrin- or caveolae-dependent endocytic pathway, nor by macropinocytosis, but requires cholesterol, tyrosine kinase, actin, dynamin and endosomal acidification, pointing towards a phagocytic mechanism. Overall, these results show that the narrow tropism of EHV-1 amongst CD172a+ cells is determined by the presence of specific cellular receptors. PMID- 26684018 TI - Phonologically Constrained Variability in L1 and L2 Production and Perception. PMID- 26684017 TI - Antimicrobial Peptides as Anti-Infectives against Staphylococcus epidermidis. AB - Staphylococcus epidermidis has emerged as the main causative agent for graft related and nosocomial infections. Rampant use of antibiotics and biofilm formed by the organism results in poor penetration of the drug and further aggravates the antibiotic resistance, emphasizing an urgent need to explore alternative treatment modalities. Antimicrobial peptides (AMPs), produced as effector molecules of the innate immunity of living organisms, have therapeutic potential that can be used to inhibit the growth of microbes. In addition, the susceptibility of a microbe to become resistant to an AMP is relatively low. The AMPs are amphipathic peptides of 12-100 residues, which have broad-spectrum activity against microbes. There are scattered reports of AMPs listed against S. epidermidis and there is an urgent need to systematically study the AMPs. Various natural AMPs as well as synthetic peptides have been investigated against S. epidermidis. These peptides have been shown to inhibit both planktonic culture and S. epidermidis biofilm effectively. The multiple modes of action in killing the organism minimize the chances for the development of resistance. This review focused on various natural and synthetic peptides that demonstrate activity against S. epidermidis. PMID- 26684019 TI - C-Type Natriuretic Peptide Analog as Therapy for Achondroplasia. AB - Fibroblast growth factor receptor 3 (FGFR3) is an important regulator of bone formation. Gain-of-function mutations in the FGFR3 gene result in chondrodysplasias which include achondroplasia (ACH), the most common form of dwarfism, in which skull, appendicular and axial skeletons are affected. The skeletal phenotype of patients with ACH showed defective proliferation and differentiation of the chondrocytes in the growth plate cartilage. Both endochondral and membranous ossification processes are disrupted during development. At cellular level, Fgfr3 mutations induce increased phosphorylation of the tyrosine kinase receptor FGFR3, which correlate with an enhanced activation of its downstream signaling pathways. Potential therapeutic strategies have emerged for ACH. Several preclinical studies have been conducted such as the C-type natriuretic peptide (CNP) analog (BMN111), intermittent parathyroid hormone injections, soluble FGFR3 therapy, and meclozine and statin treatments. Among the putative targets to antagonize FGFR3 signaling, CNP (or BMN111) is one of the most promising strategies. BMN111 acts as a key regulator of longitudinal bone growth by downregulating the mitogen-activated protein kinase pathway, which is activated as a result of a FGFR3 gain-of-function mutation. Preclinical studies showed that BMN111 treatment led to a large improvement in skeletal parameters in Fgfr3Y367C/+ mice mimicking ACH. In 2014, a clinical trial (phase 2) of BMN111 in pediatric patients with ACH has started. This first clinical trial marks the first big step towards real treatment for these patients. PMID- 26684020 TI - Early life events and motor development in childhood and adolescence: a longitudinal study. AB - AIM: Few studies have reported on early life risk factors for motor development outcomes past childhood. Antenatal, perinatal and neonatal factors affecting motor development from late childhood to adolescence were explored. As sex differences in motor development have been previously reported, males and females were examined separately. METHODS: Participants (n = 2868) were from the Western Australian Pregnancy Cohort Study. Obstetric and neonatal data were examined to determine factors related to motor development at 10 (n = 1622), 14 (n = 1584) and 17 (n = 1221) years. The Neuromuscular Development Index (NDI) of the McCarron Assessment of Motor Development determined offspring motor proficiency. Linear mixed models were developed to allow for changes in motor development over time. RESULTS: Maternal pre-eclampsia, Caesarean section and low income were negatively related to male and female motor outcomes. Lower percentage of optimal birthweight was related to a lower male NDI. Younger maternal age, smoking during early pregnancy and stress during later pregnancy were related to lower female NDIs. CONCLUSION: Events experienced during pregnancy were related to motor development into late adolescence. Males and females were influenced differently by antenatal and perinatal risk factors; this may be due to sex-specific developmental pathways. PMID- 26684021 TI - Low immunoglobulin A levels detected via the tissue transglutaminase assay can reveal previously undetected monoclonal proteins. AB - Increased awareness of coeliac disease and the 2009 NICE guidance has led to an increase in patients being screened for Immunoglobulin A deficiency. We have shown previously that this provides an opportunity for the early identification of other underlying primary immunodeficiency, e.g. common variable immunodeficiency. In this context, the underlying gastrointestinal problem appears to be related to bacterial overgrowth. Here, we demonstrate that in addition this also provides an opportunity to reveal underlying secondary immunodeficiency due to other causes in patients with gastrointestinal presentation, notably lymphoproliferative disorders. In one 3-month period, of 60 cases reviewed for low Immunoglobulin A, we found four new paraproteins through this testing route; one symptomatic multiple myeloma, one asymptomatic multiple myeloma, one monoclonal gammopathy of uncertain significance and one in a known chronic lymphocytic leukaemia patient. PMID- 26684022 TI - 25-Hydroxyvitamin D C3-epimer is universally present in neonatal Western Australian samples but is unlikely to contribute to diagnostic misclassification. AB - BACKGROUND: The presence of C3-epimer (C-3-epi-25-hydroxyvitamin D) in infant serum may complicate 25-hydroxyvitamin D (25(OH)D) measurement when using liquid chromatography tandem mass spectrometry assays that do not separately measure the epimer. We measured the concentration of C3-epi-25(OH)D in neonatal samples in Western Australian using umbilical cord blood samples and a liquid chromatography tandem mass spectrometry assay that separately quantifies 25(OH)D and C3-epi 25(OH)D. METHODS: A total of 120 anonymized cord blood samples were analysed using a liquid chromatography tandem mass spectrometry assay that utilizes two CSH fluoro-phenyl columns in series. Chromatography was performed on a Waters Acquity Ultra Performance Liquid system, and quantification was using a Waters Quattro Premier XE mass spectrometer. RESULTS: C3-epi-25(OH)D3 was detected in all umbilical cord blood samples (median 5.2 nmol/L, IQR 3.7-6.6 nmol/L) and contributed 6.6% (SD 2.6, 95% CI [6.1, 7.1]) of the total 25(OH)D concentration. Mean 25(OH)D3 measured in cord blood was 79.1 nmol/L (SD 22.7 nmol/L). A positive relationship (R(2 )= 0.35, P < 0.0005) between 25(OH)D3 levels and C3-epi 25(OH)D3 was noted in this cohort. No samples contained 25(OH)D2 or C3-epi 25(OH)D2. CONCLUSION: C3-epi-25(OH)D3 is present in all neonatal samples but contributes <10% of the total 25(OH)D concentration which is unlikely to be clinically significant. Liquid chromatography tandem mass spectrometry assays that do not separately quantify C3-epi-25(OH)D3 from other vitamin D metabolites may potentially overestimate neonatal 25(OH)D levels, but diagnostic misclassification in neonates is unlikely. PMID- 26684023 TI - Survivor-spouse dissociation and posttraumatic stress disorder: Personal and dyad relationships. AB - This study examined the relationships between dissociation and posttraumatic stress disorder (PTSD) symptoms among injured survivors of terror attacks and their spouses (N = 210), specifically exploring survivor-spouse dyadic associations. Structural equation modeling and the actor-partner interdependence model were used to test the bidirectional dyadic association of both the survivors' and the spouses' dissociation with PTSD symptoms. The results demonstrated a positive association both between the survivors' trait dissociation and PTSD symptoms and between the spouses' trait dissociation and their PTSD symptoms. However, no significant associations were found at the bidirectional level. Taken together, our findings shed new light on the role of trait dissociation in PTSD. Although trait dissociation is associated with higher PTSD symptoms for both survivors and their spouses, its role may be limited in the bidirectional partner context. Theoretical and clinical implications of the findings are discussed. PMID- 26684024 TI - Muscle fiber conduction velocity and fractal dimension of EMG during fatiguing contraction of young and elderly active men. AB - Over the past decade, linear and nonlinear surface electromyography (EMG) variables highlighting different components of fatigue have been developed. In this study, we tested fractal dimension (FD) and conduction velocity (CV) rate of changes as descriptors, respectively, of motor unit synchronization and peripheral manifestations of fatigue. Sixteen elderly (69 +/- 4 years) and seventeen young (23 +/- 2 years) physically active men (almost 3-5 h of physical activity per week) executed one knee extensor contraction at 70% of a maximal voluntary contraction for 30 s. Muscle fiber CV and FD were calculated from the multichannel surface EMG signal recorded from the vastus lateralis and medialis muscles. The main findings were that the two groups showed a similar rate of change of CV, whereas FD rate of change was higher in the young than in the elderly group. The trends were the same for both muscles. CV findings highlighted a non-different extent of peripheral manifestations of fatigue between groups. Nevertheless, FD rate of change was found to be steeper in the elderly than in the young, suggesting a greater increase in motor unit synchronization with ageing. These findings suggest that FD analysis could be used as a complementary variable providing further information on central mechanisms with respect to CV in fatiguing contractions. PMID- 26684025 TI - Determination of the ground- and excited-state dipole moments of bromocresol purple in protic and aprotic solvents. AB - Although it has been widely recognized that hydrogen bonds play a significant role in the photophysics of molecules, this phenomenon has rarely been applied to the solvatochromic method for determination of dipole moments. The difference in the dipole moment between the ground and excited state was determined in protic and aprotic solvents using both the Lippert-Mataga equation and the Bilot-Kawski equation for bromocresol purple, a molecule capable of hydrogen-bond donation and acceptance. The dipole change in protic environments was determined to be 15.2 +/ 1.0 D for the Lippert-Mataga method and 9.2 +/- 1.0 D for the Bilot-Kawski method, while the change in aprotic environments was 10.4 +/- 1.0 D and 6.7 +/- 1.0 D, respectively. Both methods highlighted the importance of hydrogen bonding in stabilizing increased charge-separation of the excited state, allowing for larger changes in dipole moments in protic environments. This study further validates a simple, rational modification to the commonly used methods that allows access to dipole-moment data on dyes with hydrogen-bonding capabilities through solvatochromic experiments. PMID- 26684026 TI - Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma. AB - Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC. PMID- 26684027 TI - Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells. AB - Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst structures were positioned in a stromal-like collagen I matrix. The molecular markers identified in the in vitro 3D models were verified in clinical samples. Network analysis of gene expression of the 3D structures indicates concurrent downregulation of transforming growth factor beta pathway genes and high levels of E-cadherin and microRNA200 (miR200) expression in the cancerous cysts and the migrating cancer cells. Transient silencing of E-cadherin expression in ovarian cancer cells disrupted cyst structures and inhibited collective cell migration. Taken together, our studies employing 3D models have shown that E-cadherin is crucial for ovarian inclusion cyst formation and collective cancer cell migration. PMID- 26684028 TI - Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. AB - There are unmet medical needs for patients with lung squamous cell carcinoma (LSCC). Therefore, in this study, we explored the antitumor potential of third generation glypican 3 (GPC3)-redirected chimeric antigen receptor (CAR) engineered T lymphocytes (CARgpc3 T cells) in tumor models of LSCC. First, we demonstrated by immunohistochemistry (IHC) that GPC3 was expressed in 66.3% of LSCC samples and in 3.3% of lung adenocarcinoma (LAD) samples but not in normal lung tissues. In the presence of GPC3-positive LSCC cells, CARgpc3 T cells were highly activated and increased in number. CARgpc3 T cells could specifically lyse GPC3-positive LSCC cells in vitro. In two established LSCC xenograft models, CARgpc3 T cells could almost completely eliminate the growth of GPC3-positive cells. Additionally, the CARgpc3 T cells were able to persist in vivo and efficiently infiltrate the cancerous tissues. Taken together, these findings indicate that CARgpc3 T cells might be a novel potential therapeutic agent for the treatment of patients with LSCC. PMID- 26684029 TI - Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer. AB - Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions (p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity (p = 0.022). In conclusion, our data suggest that ERG-fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. PMID- 26684041 TI - The first year experience of occupational therapy students at an Australian regional university: Promoting student retention and developing a regional and remote workforce. AB - OBJECTIVE: Student retention at regional universities is important in addressing regional and remote workforce shortages. Students attending regional universities are more likely to work in regional areas. First year experience at university plays a key role in student retention. This study aimed to explore factors influencing the first year experience of occupational therapy students at a regional Australian university. DESIGN: Surveys were administered to 58 second year occupational therapy students in the first week of second year. Data were analysed using descriptive statistics, inferential statistics (Pearson chi2 ; Spearman rho) and summarising descriptive responses. SETTING: An Australian regional university. PARTICIPANTS: Second year undergraduate occupational therapy students. MAIN OUTCOME MEASURES: Factors influencing students' decisions to study and continue studying occupational therapy; factors enhancing first year experience of university. RESULTS: Fifty-four students completed the survey (93.1%). A quarter (25.9%) of students considered leaving the course during the first year. The primary influence for continuing was the teaching and learning experience. Most valued supports were orientation week (36.7%) and the first year coordinator (36.7%). CONCLUSION: The importance of the first year experience in retaining occupational therapy students is highlighted. Engagement with other students and staff and academic support are important factors in facilitating student retention. It is important to understand the unique factors influencing students' decisions, particularly those from regional and remote areas, to enter and continue in tertiary education to assist in implementing supports and strategies to improve student retention. PMID- 26684030 TI - Targeting a novel domain in podoplanin for inhibiting platelet-mediated tumor metastasis. AB - Podoplanin/Aggrus is a sialoglycoprotein expressed in various cancers. We previously identified podoplanin as a key factor in tumor-induced platelet aggregation. Podoplanin-mediated platelet aggregation enhances tumor growth and metastasis by secreting growth factors and by forming tumor emboli in the microvasculature. Thus, precise analysis of the mechanisms of podoplanin-mediated platelet aggregation is critical for developing anti-tumor therapies. Here we report the discovery of a novel platelet aggregation-inducing domain, PLAG4 (81 EDLPT-85). PLAG4 has high homology to the previously reported PLAG3 and contributes to the binding of its platelet receptor CLEC-2. Mutant analyses indicated that PLAG4 exhibits a predominant platelet-aggregating function relative to PLAG3 and that conserved Glu81/Asp82/Thr85 residues in PLAG4 are indispensable for CLEC-2 binding. By establishing anti-PLAG4-neutralizing monoclonal antibodies, we confirmed its role in CLEC-2 binding, platelet aggregation, and tumor emboli formation. Our results suggest the requirement of simultaneous inhibition of PLAG3/4 for complete suppression of podoplanin mediated tumor growth and metastasis. PMID- 26684042 TI - A critical role of interleukin-1 in preterm labor. AB - Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and represents a heavy economic and social burden. Despite its broad etiology, PTB has been firmly linked to inflammatory processes. Pro-inflammatory cytokines are produced in gestational tissues in response to stressors and can prematurely induce uterine activation, which precedes the onset of preterm labor. Of all cytokines implicated, interleukin (IL)-1 has been largely studied, revealing a central role in preterm labor. However, currently approved IL-1 targeting therapies have failed to show expected efficacy in pre-clinical studies of preterm labor. Herein, we (a) summarize animal and human studies in which IL-1 or IL-1-targeting therapeutics are implicated with preterm labor, (b) focus on novel IL-1-targeting therapies and diagnostic tests, and (c) develop the case for commercialization and translation means to hasten their development. PMID- 26684043 TI - BMP morphogen gradients in flies. AB - Bone morphogenetic proteins (BMPs) act as morphogens to control patterning and growth in a variety of developing tissues in different species. How BMP morphogen gradients are established and interpreted in the target tissues has been extensively studied in Drosophila melanogaster. In Drosophila, Decapentaplegic (Dpp), a homologue of vertebrate BMP2/4, acts as a morphogen to control dorsal ventral patterning of the early embryo and anterior-posterior patterning and growth of the wing imaginal disc. Despite intensive efforts over the last twenty years, how the Dpp morphogen gradient in the wing imaginal disc forms remains controversial, while gradient formation in the early embryo is well understood. In this review, we first focus on the current models of Dpp morphogen gradient formation in these two tissues, and then discuss new strategies using genome engineering and nanobodies to tackle open questions. PMID- 26684044 TI - Pathological and Immunohistochemical Alterations of the Cornea in Congenital Corneal Opacification Secondary to Primary Congenital Glaucoma and Peters Anomaly. AB - PURPOSE: To examine the immunohistochemical alterations in the corneal stroma in Peters anomaly (PA) and congenital glaucoma (CG) compared with age-matched normals and acquired adult corneal scarring (AACS). METHODS: The clinical features of PA and CG patients who underwent penetrating keratoplasty were recorded. Immunohistochemistry of cornea and control tissue (normal and acquired corneal scars) was performed with antibodies against collagen types I, III, keratan sulfate, lumican, decorin, and smooth muscle actin followed by semiquantitative analysis of immunolabeling. RESULTS: Clinical features in 2 groups were consistent with PA and CG. Microscopy showed thickened stromal collagen bundles in PA (n = 15), CG (n = 11), and AACS (n = 20) compared with normals (n = 18). PA and CG had distinct immunophenotypes compared with controls. Type I collagen labeling was more intense in CG compared with PA (intensity grading (IG) 2.73 vs. 2.07; P < 0.001). Decorin, lumican, and keratan sulfate labeling was significantly less intense in PA versus AACS (IG; 1.91, 0.38, 1.75 in PA and 2.7, 1.11, 2.61 in AACS. respectively; P = 0.002, P = 0.001 and P = 0.004) and normals (IG 1.92, 1.06, 2.59 respectively; P < 0.001, P < 0.001 and P = 0.005). Collagen I labeling was less intense in CG versus AACS (IG 2.73 vs. 3.09) (P = 0.007). Collagen III labeling was more intense in PA/CG than in normals (IG 0.9, 0.64, 0.62 retrospectively) (P < 0.001 in both). CONCLUSIONS: The immunophenotype of the corneal scar in PA and CG differs from normal corneas and so does PA from AACS. The similarities between CG and AACS suggest that CG scarring has an acquired component. PMID- 26684045 TI - Unique Presentation of Corneal Opacity in Peters Plus Syndrome: An Unusual Form of Peters Anomaly Showing Tissue Repair in Serial Analysis. AB - PURPOSE: To report an unusual case of bilateral Peters anomaly in Peters Plus syndrome. METHODS: Systematic analysis and description of relevant clinical features, histopathological, and genetic findings. RESULTS: A premature neonate, born after 34 weeks of gestation, presented with typical features of Peters Plus syndrome and bilateral corneal opacification with central clearing. Peters Plus syndrome was confirmed by the identification of a homozygous mutation in the B3GALTL gene. When a flat anterior chamber was observed and perforation was suspected both corneas necessitated corneal transplantation (left cornea transplanted at 4 weeks of age, right cornea at the age of 9 weeks). Histopathological analysis of the left cornea revealed a central defect with absence of all corneal layers except for the corneal epithelium. The right cornea revealed central absence of the corneal endothelium and Descemet membrane as well, but the central stroma consisted of a cellular meshwork rich in fibroblasts. There were no signs of iridocorneal or keratolenticular adhesions. CONCLUSIONS: We report the histopathology of serially obtained left and right cornea of a premature neonate with Peters Plus syndrome. As demonstrated in the left cornea, the child had a central defect of all corneal layers except for the corneal epithelium. Histopathological analysis of the right cornea obtained 5 weeks later revealed that the defect had induced fibrovascular tissue repair. The sequence of events we report in the corneas of our patient may help to better understand the pathogenesis of corneal (and anterior chamber) abnormalities in Peters Plus syndrome. PMID- 26684046 TI - Clinical Outcomes After SMILE and Femtosecond Laser-Assisted LASIK for Myopia and Myopic Astigmatism: A Prospective Randomized Comparative Study. AB - PURPOSE: To compare the clinical outcomes of small-incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK) for the correction of myopia and myopic astigmatism. METHODS: In this prospective, randomized, comparative study, SMILE surgery was performed in 113 eyes with a mean spherical equivalent (MSE) of -5.22 +/- 1.70 diopters (D) and FS-LASIK was performed in 84 eyes with an MSE of -5.18 +/- 1.93 D. Contrast sensitivity and uncorrected and corrected distance visual acuities were measured preoperatively and 1 day, 1 week, 1, 3, and 6 months postoperatively. Higher-order aberrations were evaluated preoperatively and 6 months postoperatively. RESULTS: At postoperative day 1, the uncorrected distance visual acuity in the FS-LASIK group was better (P < 0.05), whereas no statistically significant difference was found at 6 months postoperatively (P = 0.9). There was no significant difference in terms of logMAR corrected distance visual acuity and MSE during the 6 months of follow-up between the SMILE and FS-LASIK groups (all P > 0.05). The contrast sensitivity in the SMILE group was lower at 1 day and 1 week postoperatively (all P < 0.05). The spherical aberration at 6 mm diameter at 6 months postoperatively was lower (P < 0.05) in the SMILE group (0.12 +/- 0.22 MUm) than in the FS-LASIK group (0.28 +/- 0.26 MUm). CONCLUSIONS: Both FS-LASIK and SMILE procedures achieved good visual outcomes in the correction of myopia and myopic astigmatism. SMILE had a lower induction rate of spherical aberration at 6 months postoperatively in the analysis of 6 mm diameter than that of FS-LASIK. PMID- 26684047 TI - Association Between Menstrual Irregularity and Dry Eye Disease: A Population Based Study. AB - PURPOSE: To determine whether dry eye disease (DED) is associated with irregular menstruation among Korean women. METHODS: In this population-based study, we randomly selected 6502 women (19-50 year olds) from nationally representative participants in the fifth annual Korea National Health and Nutrition Examination Survey (2010-2012). Data were analyzed using logistic regression to evaluate the association between menstrual irregularity and DED, while controlling for demographic characteristics, lifestyle factors, and parity. RESULTS: After adjusting for the women's demographic characteristics, age and body mass index, lifestyle factors (smoking, alcohol consumption, physical activity, and residential area), and parity, we found that menstrual irregularity was associated with an increased risk of DED (odds ratio, 1.49; 95% confidence interval, 1.02-2.17) and DED symptoms (odds ratio, 1.43; 95% confidence interval, 1.09-1.89). CONCLUSIONS: We found a significant association between DED and menstrual irregularity. PMID- 26684048 TI - Quantification of Astigmatism Induced by Pterygium Using Automated Image Analysis. AB - PURPOSE: To determine the factors influencing pterygium-induced astigmatism (PIA) and to develop a prediction model of PIA using these factors. METHODS: This cross sectional study included 97 eyes of 97 patients who underwent a pterygium excision and a limbal conjunctival autograft. Anterior segment photographs were taken preoperatively, and corneal topography was done preoperatively and at 3 months postoperatively. PIA was defined as the vector difference between the topographic astigmatism preoperatively and at 3 months postoperatively. Image analysis was performed using anterior segment photographs to measure the relative length (RL) (horizontal length of pterygium invading the cornea/horizontal corneal diameter), relative width (width of pterygium invading the cornea/vertical corneal diameter), relative area (area of pterygium invading the cornea/total corneal area), and vascularity index (VI) (degree of vascularity). Association between these factors and PIA was evaluated with univariate and multivariate analyses. We also attempted to generate a model for prediction of PIA using these factors. RESULTS: Univariate analysis showed that the RL, relative width, relative area, and VI were significantly associated with PIA (P < 0.001 for all variables, Pearson coefficient (r) = 0.708, 0.555, 0.606, and 0.642, respectively). In multivariate analysis, only the RL (P < 0.001) and VI (P < 0.001) had significant correlation with PIA. A multiple regression model for PIA was generated as follows: PIA = 0.080 * RL (%) + 0.039 * VI - 0.823 (r = 0.502, F = 95.71, P < 0.001). CONCLUSIONS: Larger lengths and increased vascularity were associated with larger PIA. PIA can be predicted by evaluating the length and vascularity of pterygium involving the cornea. PMID- 26684049 TI - Keratinized Portions of the Upper and Lower Lid Margins May Have Complete Contact During Deliberate Blinking. PMID- 26684050 TI - The Rightful Role of MRI after Negative Conventional Imaging in the Management of Bloody Nipple Discharge. AB - Nipple discharge is a frequent presenting complaint at breast clinics. Bloody nipple discharge (BND) has the highest risk of malignancy, albeit low. If mammogram and ultrasound are unrevealing, central duct excision (CDE) has been considered the gold standard in its management. Magnetic resonance imaging (MRI) has been widely confirmed as a highly sensitive test for detection of breast cancer, with an accompanying high negative predictive value. This article presents a retrospective review of patients with BND and negative conventional imaging, comparing outcome of patients who went directly to CDE without MRI to those patients who underwent preoperative MRI. Of 115 patients who underwent mammography and US alone prior to CDE, eight cancers were detected (seven ductal carcinoma in situ [DCIS] and 1 IDC, 7 mm [T1b]; incidence: 7%). Of 85 patients who underwent conventional imaging followed by MRI prior to surgery, eight cancers were detected (all DCIS; incidence: 9.4%), seven of which were identified by MRI. The one false-negative MRI had subtle findings which, in retrospect, were misinterpreted; however, a clinically apparent nipple lesion prompted surgical biopsy. Of 56 patients with a negative or benign MRI, CDE was negative for malignancy in all but that one patient. Sensitivity and specificity were 87.5%/71.4%. Positive predictive value and negative predictive value (NPV) were 24.1%/98.2%. MRI should be performed in all patients with BND and negative conventional imaging. The extremely high NPV of MRI suggests that a negative study could obviate CDE in most patients unless overriding clinical factors prevail. PMID- 26684052 TI - Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift-off test of varying duration. AB - Intravoxel incoherent motion (IVIM) MRI is a method to extract microvascular blood flow information out of diffusion-weighted images acquired at multiple b values. We hypothesized that IVIM can identify the muscles selectively involved in a specific task, by measuring changes in activity-induced local muscular perfusion after exercise. We tested this hypothesis using a widely used clinical maneuver, the lift-off test, which is known to assess specifically the subscapularis muscle functional integrity. Twelve shoulders from six healthy male volunteers were imaged at 3 T, at rest, as well as after a lift-off test hold against resistance for 30 s, 1 and 2 min respectively, in three independent sessions. IVIM parameters, consisting of perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient D* and blood flow-related fD*, were estimated within outlined muscles of the rotator cuff and the deltoid bundles. The mean values at rest and after the lift-off tests were compared in each muscle using a one-way ANOVA. A statistically significant increase in fD* was measured in the subscapularis, after a lift-off test of any duration, as well as in D. A fD* increase was the most marked (30 s, +103%; 1 min, +130%; 2 min, +156%) and was gradual with the duration of the test (in 10(-3) mm(2) /s: rest, 1.41 +/- 0.50; 30 s, 2.86 +/- 1.17; 1 min, 3.23 +/- 1.22; 2 min, 3.60 +/- 1.21). A significant increase in fD* and D was also visible in the posterior bundle of the deltoid. No significant change was consistently visible in the other investigated muscles of the rotator cuff and the other bundles of the deltoid. In conclusion, IVIM fD* allows the demonstration of a task-related microvascular perfusion increase after a specific task and suggests a direct relationship between microvascular perfusion and the duration of the effort. It is a promising method to investigate non-invasively skeletal muscle physiology and clinical perfusion related muscular disorders. PMID- 26684051 TI - Feasibility and repeatability of localized (31) P-MRS four-angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T. AB - Phosphorus ((31) P) MRS, combined with saturation transfer (ST), provides non invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T1 (app) measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four-angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra-high-field MR system, to accelerate the measurement of both Pi -to-ATP and PCr-to-ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth-resolved surface coil MRS (DRESS)-localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, Pi -to ATP and PCr-to-ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS-localized FAST method. The repeatability of PCr-to-ATP and Pi -to-ATP exchange rate constants, determined by the slab-selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr-to-ATP metabolic flux decreased (from FCK = 8.21 +/- 1.15 mM s(-1) to FCK = 3.86 +/- 1.38 mM s(-1) ) and the Pi -to-ATP flux increased (from FATP = 0.43 +/- 0.14 mM s(-1) to FATP = 0.74 +/- 0.13 mM s(-1) ). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS-localized FAST method at 7 T. PMID- 26684054 TI - Aluminium, nickel, cadmium and lead in candy products and assessment of daily intake by children in Spain. AB - Aluminium (Al), nickel (Ni), cadmium (Cd) and lead (Pb) levels in a total of 263 samples of 12 types of candies widely consumed in Spain, were evaluated. Samples were analysed using an ICP-MS method after acidic sample mineralization. Concentration ranges of Al, Ni, Cd and Pb were 21.28-62.91 ug g(-1), 0.40-1.27 ug g(-1), 0.12-1.01 ug g(-1) and 1.03-7.14 ug g(-1), respectifgvely. Statistically significant positive correlations were calculated between concentrations of Ni-Al and Pb-Cd (p-values < 0.05). Taking into consideration the relatively high metal content, together with the high caloric density of these products, as well as high content of particular nutrients such as sugars that can induce development of certain pathologies like obesity and caries, indicate that frequent consumption of candy products is not recommended. PMID- 26684053 TI - Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging. AB - An improved pre-clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)-labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet-induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo spin-echo and gradient-echo sequences, and a cardiorespiratory-gated steady-state cine gradient-echo sequence. In vitro validation studies performed in phantoms composed of 20 mM Eu-HPDO3A, 20 mM Yb-HPDO3A, or saline demonstrated similar CEST contrast by spin-echo and gradient-echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu-HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 * 10(-3) ng/cell in Eu-HPDO3A-labeled cells and 2.3 * 10(-5) ng/cell in saline-labeled cells. In vivo cardioCEST imaging of labeled cells at +/-15 ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu-HPDO3A-labeled cells when compared with surrounding myocardium or saline-labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet-induced obesity by acquiring pairs of cardioCEST images at +/-1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high-fat diet or a corresponding control low-fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high-fat diet. The selective visualization of paraCEST-labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. PMID- 26684055 TI - The role of awareness campaigns in the improvement of separate collection rates of municipal waste among university students: A Causal Chain Approach. AB - One of the main objectives of municipal waste management policies is to improve separate collection, both quantitatively and qualitatively. Several factors influence people behavior to recycling and, consequently, they play an important role to achieve the goals proposed in the management policies. People can improve separate collection rates because of a wide range of causes with different weight. Here, we have determined the uplift in probability to improve separate collection of municipal waste created by the awareness campaigns among 806 undergraduate students at Universitat Rovira i Virgili (Catalonia) by means of the Causal Chain Approach, a probabilistic method. A 73.2% state having improved separate collection in recent years and the most of them (75.4%) remember some awareness campaign. The results show the uplift in probability to improve separate collection attributable to the awareness campaigns is 17.9%. They should be taken into account by policy makers in charge of municipal waste management. Nevertheless, it must be assumed an awareness campaign will never be sufficient to achieve the objectives defined in municipal waste management programmes. PMID- 26684056 TI - Recycling of blast furnace sludge by briquetting with starch binder: Waste gas from thermal treatment utilizable as a fuel. AB - Steel plants generate significant amounts of wastes such as sludge, slag, and dust. Blast furnace sludge is a fine-grained waste characterized as hazardous and affecting the environment negatively. Briquetting is one of the possible ways of recycling of this waste while the formed briquettes serve as a feed material to the blast furnace. Several binders, both organic and inorganic, had been assessed, however, only the solid product had been analysed. The aim of this study was to assess the possibilities of briquetting using commonly available laundry starch as a binder while evaluating the possible utilization of the waste gas originating from the thermal treatment of the briquettes. Briquettes (100g) were formed with the admixture of starch (UNIPRET) and their mechanical properties were analysed. Consequently, they were subjected to thermal treatment of 900, 1000 and 1100 degrees C with retention period of 40min during which was the waste gas collected and its content analysed using gas chromatography. Dependency of the concentration of the compounds forming the waste gas on the temperature used was determined using Principal component analysis (PCA) and correlation matrix. Starch was found to be a very good binder and reduction agent, it was confirmed that metallic iron was formed during the thermal treatment. Approximately 20l of waste gas was obtained from the treatment of one briquette; main compounds were methane and hydrogen rendering the waste gas utilizable as a fuel while the greatest yield was during the lowest temperatures. Preparation of blast furnace sludge briquettes using starch as a binder and their thermal treatment represents a suitable method for recycling of this type of metallurgical waste. Moreover, the composition of the resulting gas is favourable for its use as a fuel. PMID- 26684057 TI - Electrical Isolation of Pulmonary Veins Using Laser Catheter in the Treatment of Paroxysmal and Persistent Atrial Fibrillation. One-year Results. AB - INTRODUCTION AND OBJECTIVES: A new laser balloon that allows visualization of atrial tissue has recently been introduced for pulmonary vein electrical isolation. The aim of this study was to evaluate the mid-term safety and efficacy of this catheter in the treatment of atrial fibrillation. METHODS: Laser balloon ablation was performed in 71 patients with paroxysmal (80%) or persistent (20%) atrial fibrillation. Arrhythmia recurrence was defined as any episode lasting longer than 30 seconds. During follow-up, regular visits were performed every 3 months with 24- to 48-hour Holter tests. RESULTS: Isolation was possible in 275 of 278 (99%) of pulmonary veins. Mean procedure and fluoroscopy times were 154 +/ 25 and 34 +/- 15minutes, respectively. A total of 89% of veins were isolated during the first attempt. The most common complication was phrenic nerve paralysis (5.6%), which appeared in only the first 18 cases. A total of 59 patients received follow-up for a mean of 420 +/- 193 days, with a rate of arrhythmia recurrence of 12% and 30%, respectively, in paroxysmal and persistent atrial fibrillation (P = .155). CONCLUSIONS: The laser balloon is a safe and effective system for pulmonary vein electrical isolation. Its advantages include the capacity to adapt to pulmonary vein anatomy using a single catheter, the efficacy with which pulmonary vein electrical isolation is achieved, and the favorable mid-term clinical progress, even for patients with persistent atrial fibrillation. PMID- 26684058 TI - Iron Status in Chronic Heart Failure: Impact on Symptoms, Functional Class and Submaximal Exercise Capacity. AB - INTRODUCTION AND OBJECTIVES: To evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. METHODS: We undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. RESULTS: A total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285 +/- 101 meters among those with impaired iron status, vs 322 +/- 113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. CONCLUSIONS: In patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation. PMID- 26684059 TI - Knowing Chinese character grammar. AB - Chinese character structure has often been described as representing a kind of grammar, but the notion of character grammar has hardly been explored. Patterns in character element reduplication are particularly grammar-like, displaying discrete combinatoriality, binarity, phonology-like final prominence, and potentially the need for symbolic rules (X->XX). To test knowledge of these patterns, Chinese readers were asked to judge the acceptability of fake characters varying both in grammaticality (obeying or violating reduplication constraints) and in lexicality (of the reduplicative configurations). While lexical knowledge was important (lexicality improved acceptability and grammatical configurations were accepted more quickly when also lexical), grammatical knowledge was important as well, with grammaticality improving acceptability equally for lexical and nonlexical configurations. Acceptability was also higher for more frequent reduplicative elements, suggesting that the reduplicative configurations were decomposed. Chinese characters present an as yet untapped resource for exploring fundamental questions about the nature of the human capacity for grammar. PMID- 26684060 TI - Why we forgive what can't be controlled. AB - Volitional control matters greatly for moral judgment: Coerced agents receive less condemnation for outcomes they cause. Less well understood is the psychological basis of this effect. Control may influence perceptions of intent for the outcome that occurs or perceptions of causal role in that outcome. Here, we show that an agent who chooses to do the right thing but accidentally causes a bad outcome receives relatively more punishment than an agent who is forced to do the "right" thing but causes a bad outcome. Thus, having good intentions ironically leads to greater condemnation. This surprising effect does not depend upon perceptions of increased intent for harm to occur, but rather upon perceptions of causal role in the obtained outcome. Further, this effect is specific to punishment: An agent who chooses to do the right thing is rated as having better moral character than a forced agent, even though they cause the same bad outcome. These results clarify how, when and why control influences moral judgment. PMID- 26684061 TI - Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib. AB - The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials. PMID- 26684062 TI - Identification of a small molecule that downregulates MITF expression and mediates antimelanoma activity in vitro. AB - Melanoma is a type of cancer arising from the melanocytes, which are the cells that make up the pigment melanin and are derived from the neural crest. There is no particularly effective therapy once the disease is metastatic, highlighting the need for discovery of novel potent agents. In this investigation, we adopted a zebrafish embryonic pigmentation model to identify antimelanoma agents by screening an in-house small molecule library. With this assay, we found that a small molecule compound, SKLB226, blocked zebrafish pigmentation and pigment cell migration. Mechanism of action studies showed that SKLB226 downregulated MITF mRNA level in both zebrafish embryos and mammalian melanoma cells. Further studies showed that it could efficiently suppress the viability and migration of mammalian melanoma cells. In summary, SKLB226 can be used as a chemical tool to study melanocyte development as well as an antimelanoma lead compound that should be subjected to further structural optimization. PMID- 26684064 TI - Sensing microorganisms in the gut triggers the immune response in Eisenia andrei earthworms. AB - The tube-within-tube body plan of earthworms is appropriate for studying the interactions of microorganisms with the immune system of body cavities such as the digestive tract and coelom. This study aims to describe the immune response on the molecular and cellular level in the coelomic cavity and the gut of the earthworm Eisenia andrei after experimental microbial challenge by administering two bacterial strains (Escherichia coli and Bacillus subtilis) or yeast Saccharomyces cerevisiae to the environment. The changes in mRNA levels of defense molecules (pattern recognition receptor CCF, lysozyme, fetidin/lysenins) in the coelomocytes and gut tissue were determined by quantitative PCR. The immune response at a cellular level was captured in histological sections, and the expression of CCF was localized using in situ hybridization. Coelomocytes respond to the presence of bacteria in the coelomic cavity by increasing the mRNA levels of defense molecules, especially CCF. The immune response in gut tissue is less affected by microbial stimulation because the epithelial cells of gut exhibit basically strong mRNA synthesis of ccf as a defense against the continuous microbial load in the gut lumen. The cellular immune response is mediated by coelomocytes released from the mesenchymal lining of the coelomic cavity. These combined immune mechanisms are necessary for the survival of earthworms in the microbially rich environment of soil. PMID- 26684065 TI - Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori. AB - The relevance of protein tyrosine phosphatase (PTP) to host-pathogen interaction is highlighted in mammalian studies, whereas less is known in insects. Here we presented the categorization of the PTP complement of silkworm and characterized their homologous relationship with human and fruit fly PTPs. Among the 36 PTP genes, ptp-h, which was proposed to be the origin of baculovirus ptp belongs to atypical VH1-like dual-specific PTP subset and encodes a catalytic active protein. The maximum expression level of Bmptp-h was at 5th instar and in fat body. Bombyx mori nucleopolyhedrovirus (BmNPV) infection potently induced its expression in silkworm larvae and in BmE cells. Knock-down of Bmptp-h by RNA interference significantly inhibited viral replication, and over-expression enhanced viral replication as determined by viral DNA abundance and BmNPV-GFP positive cells. These results suggest that BmPTP-h might be one of the host factors that is beneficial to baculovirus infection by promoting viral replication. PMID- 26684066 TI - Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation: in vitro exploratory studies. AB - OBJECTIVES: To conduct proof of principle studies that will enable development of noninvasive (respiratory) delivery systems for levothyroxine (T4). METHODS: Preformulation (solubility, stability), formulation and biopharmaceutical (in vitro absorption, transport, gene expression) studies were conducted. Calu-3 cell line was used for permeation studies. RESULTS: Solubility profiles of T4 were established in aqueous (PBS, HBSS, isotonic saline) and non-aqueous solvents (PEG 400, PEG 600, propylene glycol, glycerine). Transport of the compound across Calu 3 cells suggested involvement of active transport systems. This correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, LAT1 and LAT2) in the cell line. Diffusion characteristics showed significant absorption with no detection of T4 metabolite (triiodothyronine). Formulation studies revealed that stable formulations could be prepared using a combination of aqueous and non aqueous solvents. CONCLUSIONS: Results of the studies indicated that T4 can be absorbed effectively from the respiratory mucosa. Factors affecting stability such as pH and temperature should be taken into account during formulation development of this compound for the respiratory route. PMID- 26684063 TI - Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies. AB - Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity) = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype. PMID- 26684067 TI - Emerging Data in Pediatric Traumatic Brain Injury. PMID- 26684068 TI - Neuropsychological benefits of computer-assisted cognitive rehabilitation (using FORAMENRehab program) in children with mild traumatic brain injury or partial epilepsy: A pilot study. AB - INTRODUCTION: The number of children with different cognitive difficulties is constantly increasing. Still, too few evidence-based pediatric neurocognitive rehabilitation programs exist. The main aim of the study was to assess the efficiency and usability of computer-assisted FORAMENRehab program for training specific components of attention in children with mild traumatic brain injury (mTBI) and partial epilepsy (PE). The second aim was to specify short- and long term effects of the intervention. METHODS: Eight children between the ages of 9 12 years with attention impairment (3 with PE and 5 with mTBI) and 18 healthy controls participated. FORAMENRehab Attention software, adapted by the authors, was used for intervention. Strict intervention protocol consisting of patients completing 10 sessions over a 6-week-period to train four components of attention (sustaining, focusing, dividing, tracking) was designed and applied. Follow-up assessments were conducted after the end of the last training and 1.63 years later. RESULTS: After the intervention patients' sustained and complex attention improved. Long-term follow-up revealed continuing positive rehabilitation effects. 100% compliance suggested that the used method is attractive for children. CONCLUSIONS: These preliminary results of the pilot study give reason to presume that the method is effective in attention impairment remediation. However, more thorough research is needed. PMID- 26684069 TI - White matter alterations in youth with acute mild traumatic brain injury. AB - PURPOSE: To examine acute alterations in white matter (WM) diffusion based on diffusion tensor imaging (DTI) in youth with mild traumatic brain injury (mTBI) relative to orthopedic injury (OI) controls. METHODS: A prospective cohort study of 23 patients with mTBI and 20 OI controls ages 11-16 years were recruited from the emergency department (ED). DTI was performed within 96 hours. Voxel based analysis quantified group differences for DTI indices: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The Post Concussion Symptom Scale assessed symptom burden. RESULTS: Youth with mTBI had significantly higher symptom burdens in the ED and at scanning than controls. The mTBI group had significantly higher levels of FA and AD in several WM regions including the middle temporal gyrus WM, superior temporal gyrus WM, anterior corona radiata, and superior longitudinal fasciculus. The mTBI group had significantly lower levels of MD and/or RD in a few WM regions including the middle frontal gyrus WM and anterior corona radiata. Diffusion alterations correlated poorly with acute symptom burden. CONCLUSIONS: Alterations of diffusivity were detected in spatially heterogeneous WM regions shortly after mTBI in youth. The pattern of alterations may reflect restrictive water diffusion in WM early post-injury. PMID- 26684070 TI - Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI). AB - PURPOSE: The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. METHODS: Nineteen adolescents on average 7.5 months post-mTBI completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. The comparison group included 19 healthy controls matched to the mTBI group for demographic variables and N-back task performance. RESULTS: There were no between-group differences for cognition or behavior ratings. The expected decreased accuracy and increased reaction time as N-back task difficulty increased were apparent. The mTBI group showed significantly greater brain activation than controls during the most difficult working memory load condition. CONCLUSION: Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of symptom recovery, which could have important clinical implications. PMID- 26684071 TI - Altered functional connectivity in children with mild to moderate TBI relates to motor control. AB - PURPOSE: Functionally relevant alterations in resting state fMRI (rs-fMRI) connectivity have been identified in adults with traumatic brain injury (TBI). We evaluated rs-fMRI connectivity in children with TBI and explored the relationship between altered connectivity and measures of neurological function. METHODS: Rs fMRI was obtained in 14 children after TBI and 14 controls matched for age, sex, and handedness. Whole-brain connectivity was evaluated separately for the default mode network (DMN) and dorsal attention network (DAN); Between-group contrasts identified regions with altered connectivity between TBI and control cohorts. In children with TBI, the relationships between regions of altered connectivity and performance on relevant functional measures were examined. RESULTS: Compared to controls, children with TBI showed significantly greater connectivity between DMN and right dorsal premotor cortex (RdPM) and between DAN and bilateral sensorimotor cortex (SM1). In children with TBI, greater DMN-RdPM connectivity was associated with worse motor performance whereas greater DAN-LSM1 connectivity was associated with better motor performance; furthermore, DMN-RdPM and DAN-LSM1 connectivity were negatively correlated. CONCLUSION: Rs-fMRI reveals significant altered connectivity in children with TBI compared to controls. After TBI in children, patterns of altered connectivity appear divergent, with increased DMN motor network connectivity associated with worse motor control whereas increased DAN-motor network connectivity appears compensatory. PMID- 26684073 TI - Balance and mobility in clinically recovered children and adolescents after a mild traumatic brain injury. AB - PURPOSE: To compare the ability of clinical balance measures to detect differences between children recovered from a mild Traumatic Brain Injury (mTBI) and healthy controls. METHODS: A cross-sectional study, with twenty-six children with mTBI and twenty-two age-matched controls was conducted. Balance was evaluated on three scales: Bruininks- Osteresky Test-second edition; Balance Error Scoring System and Community Balance and Mobility Scale, along with gait analysis of three paradigms (self-selected paced walking, obstacle crossing and tandem walking), under single and dual-task conditions, using GAITRite?scriptsize(r) walkway. Independent sample t-tests (alpha = 0.05) were used to identify group differences. Dual-Task Cost (DTC) was analyzed using repeated measures ANOVA and t-tests. Discriminant analysis predicted which balance measure best identified the groups. RESULTS: Children with mTBI performed worse on all balance scales (p< 0.05). Gait parameters were significantly better for the controls. There were no group differences on the motor and cognitive DTC. The Community Balance and Mobility Scale and gait parameters including velocity at obstacle crossing and parameters for tandem walking, best discriminated the groups. CONCLUSION: Clinical balance assessments may need to include static and dynamic measures, to capture possible performance difficulties. The inclusion of these measures will enhance clinical decision making and prevent premature return to physical activities in children with mTBI. PMID- 26684072 TI - Neural substrates of inhibitory and emotional processing in adolescents with traumatic brain injury. AB - PURPOSE: Disturbances of emotional regulation and social difficulties are common in children and adolescents with traumatic brain injury (TBI). Recent research suggests that developments within ''socio-emotional'' brain systems during early adolescence and more protracted development of "cognitive control'' systems have implications for emotional and behavioral regulation during adolescence. However, few functional neuroimaging studies have directly examined the interaction of these neuropsychological processes in adolescents with TBI. The current study examined how affective processing might modulate inhibitory processing in an Emotional Go/NoGo paradigm. METHOD: The study uses a cross-sectional, age, gender, and maternal education matched design.A response inhibition paradigm (i.e., the Go/NoGo task with emotional faces) was used to examine emotional cognition interaction in 11 adolescents with complicated mild to moderate TBI, at least 12 months post injury, and 14 typically-developing (TD) adolescents using functional magnetic resonance imaging (fMRI). Participants saw adult facial expressions of emotions (happy, sad, fearful, and angry) and were instructed to respond (''go'') on all expressions other than angry (''no-go''). RESULTS: Preliminary results (p= 0.001 uncorrected, cluster size = 50) showed higher levels of inhibition-related activation in TD adolescents than in adolescents with TBI in several brain regions including anterior cingulate and motor/premotor regions. CONCLUSION: These results suggest that TBI in adolescence might alter brain activation patterns and interrupt the development of brain networks governing emotion-cognition interactions. PMID- 26684074 TI - Anxiety disorders in children and adolescents in the second six months after traumatic brain injury. AB - The objective of this prospective longitudinal study was to assess the nature, rate, predictive variables, and neuroimaging characteristics of novel (new-onset) anxiety disorders (compared with no novel anxiety disorders) 6-12 months after pediatric traumatic brain injury (TBI). Psychiatric and psychosocial interviews were administered to children who sustained mild to severe TBI at baseline (soon after injury) and at the 12-month follow-up post-injury (n= 125). The psychiatric outcome of children 12-months post-injury revealed that novel anxiety disorders present in the second six months after TBI were heterogeneous and occurred in 13 (10.4%) participants. Novel anxiety disorder was significantly associated with concurrent novel depressive disorder and with novel personality change due to TBI. Novel anxiety disorder was marginally associated with younger age at injury and with pre-injury anxiety disorder in univariate analyses. Age at injury, pre injury anxiety disorder, and personality change due to TBI were each significantly and independently related to novel anxiety disorder in a logistic regression analysis. There were no significant neuroimaging group differences. These findings suggest that the emergence of novel anxiety disorder after TBI might be related to a broader problem of affective dysregulation especially in younger children and those with a vulnerability even to pre-injury anxiety disorder. PMID- 26684077 TI - Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys. AB - Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26684078 TI - Particle-Film Plasmons on Periodic Silver Film over Nanosphere (AgFON): A Hybrid Plasmonic Nanoarchitecture for Surface-Enhanced Raman Spectroscopy. AB - Plasmonic systems based on particle-film plasmonic couplings have recently attracted great attention because of the significantly enhanced electric field at the particle-film gaps. Here, we introduce a hybrid plasmonic architecture utilizing combined plasmonic effects of particle-film gap plasmons and silver film over nanosphere (AgFON) substrates. When gold nanoparticles (AuNPs) are assembled on AgFON substrates with controllable particle-film gap distances, the AuNP-AgFON system supports multiple plasmonic couplings from interparticle, particle-film, and crevice gaps, resulting in a huge surface-enhanced Raman spectroscopy (SERS) effect. We show that the periodicity of AgFON substrates and the particle-film gaps greatly affects the surface plasmon resonances, and thus, the SERS effects due to the interplay between multiple plasmonic couplings. The optimally designed AuNP-AgFON substrate shows a SERS enhancement of 233 times compared to the bare AgFON substrate. The ultrasensitive SERS sensing capability is also demonstrated by detecting glutathione, a neurochemical molecule that is an important antioxidant, down to the 10 pM level. PMID- 26684079 TI - Reconstruction of hepatic venous tributary in right liver living donor liver transplantation: The importance of the inferior right hepatic vein. AB - Special care must be taken in hepatic vein reconstruction to avoid outflow block in living donor liver transplantation (LDLT) with a right liver graft. We have used cryopreserved homologous veins to reconstruct the right hepatic vein (RHV), middle hepatic vein (MHV), MHV tributaries (V5 and V8), and inferior right hepatic vein (IRHV). The reconstruction of V5, V8, and IRHV was based on the estimated congestive volume, calculated by the computed tomography volumetry, to secure the functional graft volume of 40% of the recipient standard liver volume. Among 262 right liver LDLT recipients, the number of reconstructed RHVs, MHVs, V5s, V8s, and IRHVs was 262, 48, 110, 111, and 147, respectively, and the overall patency was 95%, 100%, 36%, 58%, and 86%, respectively. Although the patency of the RHVs and MHVs was satisfactory, that of the V5s, V8s, and IRHVs was suboptimal. Patency of the IRHVs (86%, 126/147) was significantly better than that of both V5s (36%, 40/110) and V8s (58%, 64/111; P < 0.001). In addition, the estimated volume drained by IRHVs was significantly greater than that of V5s and V8s (IRHV, 176 +/- 92 mL; V5, 105 +/- 49 mL; V8, 127 +/- 60 mL; P < 0.001). The patency of IRHV was significantly improved by applying the double inferior vena cava method (93%, 94/101) when compared to the direct anastomosis to vena cava (68%, 25/37; P < 0.001). The IRHV functioned as a main drainage route in cases of an obstructed RHV. In conclusion, reconstruction of the IRHV is recommended, not only to improve the functional reserve of the graft, but also to secure multiple drainage routes of the graft. PMID- 26684080 TI - Parent Recommendations for Family Functioning With Prader-Willi Syndrome: A Rare Genetic Cause of Childhood Obesity. AB - Prader-Willi syndrome (PWS) is the most common genetic cause of childhood obesity. Neonates have hypotonia and may fail to growth and develop. Within a few years, behavioral problems occur along with insatiable hunger (hyperphagia) and the potential for excessive weight gain. The purpose of this study was to identify how families function when they have a child with PWS. DESIGN AND METHODS: This qualitative descriptive study was based on 20 face-to-face, audio taped interviews with parents. They were asked to identify family responses to PWS and offer recommendations. Data were transcribed, coded and analyzed for commonalities and themes. RESULTS: There were twelve identified themes with two overarching themes of 1) taking action and 2) caring for oneself and family. Taking action was focused on achieving what was best for the child with PWS. Caring for oneself and family attempted to assure that all in the family were healthy, content, and living a fulfilling life under their circumstances. CONCLUSIONS: This study revealed parental insight as to how they learned to creatively cope with a stressful family life. There was a recognition of inevitable sacrifice and the need for changes in expectations so as to help the child with PWS flourish while also focusing on the needs of all the members of the family. PRACTICE IMPLICATIONS: Nursing and health care providers should be aware of these issues in the provision of anticipatory guidance to families contending with this genetic disorder. PMID- 26684081 TI - Epidemics of GI.2 sapovirus in gastroenteritis outbreaks during 2012-2013 in Osaka City, Japan. AB - Sapovirus (SaV) is a causative agent of gastroenteritis in humans in both sporadic cases and outbreaks. During the period from January 2005 to August 2014, SaV was detected in 30 (5.9%) of 510 gastroenteritis outbreaks in Osaka City, Japan using real-time RT-PCR. Seasonal distribution of SaV-associated outbreaks revealed an increase during the 2011-2012 season and the highest frequency of outbreaks during the 2012-2013 season. Genotyping analysis based on the capsid region demonstrated that the most common genotype was GI.2 (36.7%), in which the strains were closely related. The comparison of complete capsid gene sequences with 18 GI.2 strains (7 strains in this study and 11 from GenBank) between 1990 and 2013 showed that GI.2 strains were classified into at least three genetic clusters (1990-2000, 2004-2007, and 2008-2013) with chronologically unique amino acid residues and accumulation of mutations in the predicted P domain, suggesting the one of the causes of emergence and spread of GI.2 strains. This study will also be helpful for understanding the evolutionary mechanism of the SaV genome. PMID- 26684082 TI - Rapid label-free profiling of oral cancer biomarker proteins using nano-UPLC-Q TOF ion mobility mass spectrometry. AB - PURPOSE: It has become quite clear that single cancer biomarkers cannot in general provide high sensitivity and specificity for reliable clinical cancer diagnostics. This paper explores the feasibility of rapid detection of multiple biomarker proteins in model oral cancer samples using label-free protein relative quantitation. EXPERIMENTAL DESIGN: MS-based label-free quantitative proteomics offer a rapid alternative that bypasses the need for stable isotope containing compounds to chemically bind and label proteins. Total protein content in oral cancer cell culture conditioned media was precipitated, subjected to proteolytic digestion, and then analyzed using a nano-UPLC (where UPLC is ultra-performance liquid chromatography) coupled to a hybrid Q-Tof ion-mobility mass spectrometry (MS). RESULTS: Rapid, simultaneous identification and quantification of multiple possible cancer biomarker proteins was achieved. In a comparative study between cancer and noncancer samples, approximately 952 proteins were identified using a high-throughput 1D ion mobility assisted data independent acquisition (IM-DIA) approach. As we previously demonstrated that interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) were readily detected in oral cancer cell conditioned media(1), we targeted these biomarker proteins to validate our approach. Target biomarker protein IL-8 was found between 3.5 and 8.8 fmol, while VEGF-A was found at 1.45 fmol in the cancer cell media. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, our data suggest that the nano-UPLC-IM-DIA bioassay is a feasible approach to identify and quantify proteins in complex samples without the need for stable isotope labeling. These results have significant implications for rapid tumor diagnostics and prognostics by monitoring proteins such as IL-8 and VEGF-A implicated in cancer development and progression. The analysis in tissue or plasma is not possible at this time, but the subsequent work would be needed for validation. PMID- 26684083 TI - Current situation of endoscopic biliary cannulation and salvage techniques for difficult cases: Current strategies in Japan. AB - In the pancreatobiliary session at Endoscopic Forum Japan (EFJ) 2015, current trends of routine biliary cannulation techniques and salvage techniques for difficult biliary cannulation cases were discussed. Endoscopists from nine Japanese high-volume centers along with two overseas centers participated in the questionnaires and discussion. It was concluded that, currently, in Western countries, the wire-guided cannulation (WGC) technique is favored during initial cannulation attempts. However, the conventional technique using an endoscopic retrograde cholangiopancreatography catheter with contrast medium injection is still used as first choice at most Japanese high-volume centers. The WGC technique is used as the second choice at some institutions only. After failed biliary cannulation attempts, the initial salvage option preferred in most centers includes pancreatic guidewire placement, followed by precut techniques as the second salvage choice. Among several precut techniques, the free-hand needle knife sphincterotomy with cutting upwards from the pancreatic duct is most popular. Endoscopic ultrasonography-guided rendezvous technique is also carried out as a final salvage option at select institutions. PMID- 26684085 TI - Helping leaders lead the way. PMID- 26684086 TI - For human needs, some veterinary clinics are turning to a professional: Social workers see a place for themselves in veterinary practice. PMID- 26684087 TI - Full-thickness skin grafts in dogs and cats versus humans. PMID- 26684088 TI - Precision medicine: an opportunity for a paradigm shift in veterinary medicine. PMID- 26684089 TI - What Is Your Diagnosis? Bacterial osteomyelitis with secondary encephalitis. PMID- 26684090 TI - What Is Your Diagnosis? Osteochondrotic lesions. PMID- 26684091 TI - What Is Your Neurologic Diagnosis? Intervertebral Disk Disease. PMID- 26684092 TI - Pathology in Practice. Peritoneal Mesothelioma With Metastasis to Adrenal glands, Heart, and Lungs. PMID- 26684093 TI - Evaluation of the mydriatic effects of topical administration of rocuronium bromide in Hispaniolan Amazon parrots (Amazona ventralis). AB - OBJECTIVE :To determine the mydriatic effects of topical rocuronium bromide administration in Hispaniolan Amazon parrots (Amazona ventralis) and to identify any adverse effects associated with treatment. DESIGN: Randomized crossover study. ANIMALS: 8 healthy adult Hispaniolan Amazon parrots. PROCEDURES: Rocuronium bromide (20 MUL/eye; 10 mg/mL) or saline (20 MUL/eye; 0.9% NaCl) solution was administered in both eyes of each bird with a 26-day washout period. The birds were manually restrained in lateral recumbency with the apex of the cornea positioned upward for 2 minutes following administration in each eye. Infrared pupillometry and direct pupillary light reflex measurements were used to evaluate the mydriatic effects. Pupillary measurements were recorded prior to administration and every 20 minutes for 2 hours after administration, then hourly for a total of 7 hours. A brief physical examination was performed, direct pupillary light reflex was tested, and fluorescein staining was performed on each eye of each bird 24 hours after administration. RESULTS: A significant difference in pupillary diameter for the active versus control treatment group was noted from 20 to 360 minutes after drug administration, but not at 420 minutes. Minimal adverse effects were noted. Three birds had transient inferior eyelid paresis noted in both eyes after receiving rocuronium; 24 hours after the treatment, no differences in ocular measurements existed between the active and control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that topical rocuronium bromide administration may be safely used for pupillary dilation in Hispaniolan Amazon parrots and could be used for clinical evaluation, fundus imaging, and surgical interventions involving the lens and posterior segment in this species. PMID- 26684094 TI - Palliative radiation therapy for solid tumors in dogs: 103 cases (2007-2011). AB - OBJECTIVE: To evaluate the clinical response, adverse effects, and outcomes associated with palliative radiation therapy (PRT) in dogs with various solid tumor types at various body locations. DESIGN: Retrospective case series. ANIMALS: 103 dogs with solid tumors. PROCEDURES: Medical records for dogs with solid tumors treated with PRT between July 2007 and January 2011 at a veterinary teaching hospital were reviewed. Data collected included signalment, tumor type and location, initial staging results, PRT protocol, other tumor-specific treatments, patient and tumor response, outcome, and acute and chronic adverse effects. Median progression-free survival time, median survival time (MST), and other descriptive statistics were calculated. RESULTS: Types of tumors treated included carcinoma, sarcoma, melanoma, primary bone tumor, mast cell tumor, and ameloblastoma. For all dogs, the overall tumor and clinical response rates to PRT were 75% and 77%, respectively, and the MST was 134 days, but those responses varied substantially among tumor types. Dogs that developed a positive clinical response or maintained stable disease after PRT had a significantly longer MST than did dogs with progressive disease. Tumor location was not significantly associated with median progression-free survival time or MST. Most dogs tolerated the PRT well. Acute and chronic adverse effects were observed in 57 and 8 dogs, respectively, but were generally self-limiting. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with various types of solid tumors that received PRT had objective beneficial responses and an improvement in quality of life that was positively associated with survival time. PMID- 26684095 TI - Short-term clinical outcome of laparoscopic liver biopsy in dogs: 106 cases (2003 2013). AB - OBJECTIVE: To describe the operative technique, complications, and conversion rates for laparoscopic liver biopsy (LLB) in dogs and evaluate short-term clinical outcome for dogs that underwent the procedure. DESIGN: Retrospective case series. ANIMALS: 106 client-owned dogs. PROCEDURES: Medical records were reviewed to identify dogs that underwent an LLB with a single-port or multiport technique at either of 2 veterinary teaching hospitals from August 2003 to September 2013. Demographic and laboratory data, preoperative administration of fresh frozen plasma, procedural and diagnostic information, intraoperative complications, and survival to discharge were recorded. The LLB specimens were obtained with 5-mm laparoscopic biopsy cup forceps and a grasp-and-twist technique. RESULTS: Prior to surgery, 25 of 94 (27%) dogs had coagulopathy (prothrombin time or partial thromboplastin time greater than the facility reference ranges, regardless of platelet count). Twenty-one dogs were thrombocytopenic, 14 had ascites, and 14 received fresh frozen plasma transfusion before surgery. In all cases, biopsy samples collected were of sufficient size and quality for histopathologic evaluation. Two dogs required conversion to an open laparotomy because of splenic laceration during initial port placement. One hundred one of 106 dogs survived to discharge; 5 were euthanized during hospitalization owing to progression of liver disease and poor prognosis. CONCLUSIONS AND CLINICAL RELEVANCE: Single-port and multiport LLB were found to be effective, minimally invasive diagnostic techniques with a low rate of complications. Results suggested LLB can be safely used in dogs with underlying coagulopathies and advanced liver disease. PMID- 26684096 TI - Use of a split-thickness soft palate hinged flap and bilateral buccal mucosal rotation flaps for one-stage repair of a bilateral hypoplastic soft palate in a dog. AB - CASE DESCRIPTION: A 14-week-old 8.5-kg (18.7-lb) sexually intact female Springer Spaniel was evaluated because of chronic rhinitis with bilateral mucopurulent nasal discharge. The dog had a history since birth of sneezing and oronasal reflux of food and liquid. CLINICAL FINDINGS: Oral examination under anesthesia revealed a short, incompletely formed soft palate with bilateral clefts. A pseudouvula was not a prominent feature of the condition in this dog. TREATMENT AND OUTCOME: The dog underwent 1-stage reconstruction of the soft palate by means of a split-thickness soft palate hinged flap and bilateral buccal mucosal rotation flaps. Long-term follow-up obtained 3 years after surgery revealed the dog to be in good general health, with resolution of oronasal reflux; however, occasional episodes of mild sneezing and nasal discharge persisted. Oral examination under sedation revealed attenuation of the bilateral clefts; however, a normal soft palate length was not achieved. CLINICAL RELEVANCE: Compared with previously described techniques, this technique offered the possibility of 1 stage reconstruction of the soft palate in dogs, rather than having 2 staged procedures performed, and a robust tissue combination that was expected to be less prone to trauma. This technique may be particularly suitable for affected dogs where a pseudouvula is not a prominent feature and appears to be applicable to a variety of skull morphologies. Owners should be made aware that the absence of normal palatine muscle within the reconstructed palate may affect function, but even where normal function is not regained, a good quality of life with minimal clinical signs may be achieved. PMID- 26684097 TI - Validation of a portable pneumatic captive bolt device as a one-step method of euthanasia for use in depopulation of feedlot cattle. AB - OBJECTIVE: To validate the effectiveness of a penetrating captive bolt device with a built-in low-pressure air channel pithing mechanism (PCBD) as a 1-step method for euthanasia of cattle. DESIGN: Clinical trial. ANIMALS: 66 feedlot steers and heifers (weight, 227 to 500 kg [500 to 1,100 lb]) that were not expected to survive or finish the feeding period with their cohorts. PROCEDURES: Cattle were transported to a university facility and euthanized with the PCBD. For each calf, clinical variables were monitored and recorded immediately before and for at least 10 minutes after application of the PCBD. Following euthanasia, the head of each calf was removed and trauma to the brain and skull was assessed and scored. RESULTS: Death was successfully achieved with the PCBD without application of an ancillary technique in all 66 cattle; however, 4 (6%) cattle required a second or third shot from the PCBD because of technical errors in its placement. All shots from the PCBD that entered the cranial vault successfully rendered cattle unconscious without a return to sensibility. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the PCBD was an effective 1-step method of euthanasia for use in mass depopulation of feedlot cattle. PMID- 26684098 TI - Characteristics of the labor market for veterinary technician specialists in 2013. AB - OBJECTIVE: To determine characteristics of the labor market for veterinary technician specialists (VTSs) during 2013 and identify characteristics significantly associated with pay rate for VTSs. DESIGN: Survey. SAMPLE POPULATION: 351 VTSs. PROCEDURES: A 29-question, multiple-choice survey was sent in early 2014 to all individuals (n = 786) who had been certified as VTSs and for whom an email address could be identified. RESULTS: Weighted mean pay rate for respondents was $23.50/h; 51.3% (180/351) of respondents received a raise after obtaining VTS certification. Being male, having attended graduate school, having > 4 years of VTS experience, holding a supervisory or management position, being employed by an academic employer or referral practice, and working in the Northeast or outside the United States increased the overall odds of receiving a higher pay rate as a VTS, once other variables were controlled. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that gender, work experience, and job characteristics were significantly associated with pay rate for VTSs. PMID- 26684099 TI - Editorial. PMID- 26684100 TI - Many-Body Localization in the Presence of a Single-Particle Mobility Edge. AB - In one dimension, noninteracting particles can undergo a localization delocalization transition in a quasiperiodic potential. Recent studies have suggested that this transition transforms into a many-body localization (MBL) transition upon the introduction of interactions. It has also been shown that mobility edges can appear in the single particle spectrum for certain types of quasiperiodic potentials. Here, we investigate the effect of interactions in two models with such mobility edges. Employing the technique of exact diagonalization for finite-sized systems, we calculate the level spacing distribution, time evolution of entanglement entropy, optical conductivity, and return probability to detect MBL. We find that MBL does indeed occur in one of the two models we study, but the entanglement appears to grow faster than logarithmically with time unlike in other MBL systems. PMID- 26684101 TI - One-to-One Mapping between Steering and Joint Measurability Problems. AB - Quantum steering refers to the possibility for Alice to remotely steer Bob's state by performing local measurements on her half of a bipartite system. Two necessary ingredients for steering are entanglement and incompatibility of Alice's measurements. In particular, it is known that for the case of pure states of maximal Schmidt rank the problem of steerability for Bob's assemblage is equivalent to the problem of joint measurability for Alice's observables. We show that such an equivalence holds in general; namely, the steerability of any assemblage can always be formulated as a joint measurability problem, and vice versa. We use this connection to introduce steering inequalities from joint measurability criteria and develop quantifiers for the incompatibility of measurements. PMID- 26684102 TI - Observation of a Superradiant Mott Insulator in the Dicke-Hubbard Model. AB - It is well known that the bosonic Hubbard model possesses a Mott insulator phase. Likewise, it is known that the Dicke model exhibits a self-organized superradiant phase. By implementing an optical lattice inside of a high-finesse optical cavity, both models are merged such that an extended Hubbard model with cavity mediated infinite range interactions arises. In addition to a normal superfluid phase, two superradiant phases are found, one of them coherent and hence superfluid and one incoherent Mott insulating. PMID- 26684103 TI - Heavy Tails in the Distribution of Time to Solution for Classical and Quantum Annealing. AB - For many optimization algorithms the time to solution depends not only on the problem size but also on the specific problem instance and may vary by many orders of magnitude. It is then necessary to investigate the full distribution and especially its tail. Here, we analyze the distributions of annealing times for simulated annealing and simulated quantum annealing (by path integral quantum Monte Carlo simulation) for random Ising spin glass instances. We find power-law distributions with very heavy tails, corresponding to extremely hard instances, but far broader distributions-and thus worse performance for hard instances-for simulated quantum annealing than for simulated annealing. Fast, nonadiabatic, annealing schedules can improve the performance of simulated quantum annealing for very hard instances by many orders of magnitude. PMID- 26684104 TI - Quadratic Stochastic Euclidean Bipartite Matching Problem. AB - We propose a new approach for the study of the quadratic stochastic Euclidean bipartite matching problem between two sets of N points each, N?1. The points are supposed independently randomly generated on a domain Omega?R^{d} with a given distribution rho(x) on Omega. In particular, we derive a general expression for the correlation function and for the average optimal cost of the optimal matching. A previous ansatz for the matching problem on the flat hypertorus is obtained as a particular case. PMID- 26684105 TI - Beyond the Horizon Distance: LIGO-Virgo can Boost Gravitational-Wave Detection Rates by Exploiting the Mass Distribution of Neutron Stars. AB - The masses of neutron stars in neutron star binaries are observed to fall in a narrow mass range around ~1.33M_{?}. We explore the advantage of focusing on this region of the parameter space in gravitational-wave searches. We find that an all sky (externally triggered) search with an optimally reduced template bank is expected to detect 14% (61%) more binary mergers than without the reduction. A reduced template bank can also represent significant improvement in technical cost. We also develop a more detailed search method using binary mass distribution, and find a sensitivity increase similar to that due to the reduced template bank. PMID- 26684106 TI - Neutron-Star-Black-Hole Binaries Produced by Binary-Driven Hypernovae. AB - Binary-driven hypernovae (BdHNe) within the induced gravitational collapse paradigm have been introduced to explain energetic (E_{iso}?10^{52} erg), long gamma-ray bursts (GRBs) associated with type Ic supernovae (SNe). The progenitor is a tight binary composed of a carbon-oxygen (CO) core and a neutron-star (NS) companion, a subclass of the newly proposed "ultrastripped" binaries. The CO-NS short-period orbit causes the NS to accrete appreciable matter from the SN ejecta when the CO core collapses, ultimately causing it to collapse to a black hole (BH) and producing a GRB. These tight binaries evolve through the SN explosion very differently than compact binaries studied in population synthesis calculations. First, the hypercritical accretion onto the NS companion alters both the mass and the momentum of the binary. Second, because the explosion time scale is on par with the orbital period, the mass ejection cannot be assumed to be instantaneous. This dramatically affects the post-SN fate of the binary. Finally, the bow shock created as the accreting NS plows through the SN ejecta transfers angular momentum, braking the orbit. These systems remain bound even if a large fraction of the binary mass is lost in the explosion (well above the canonical 50% limit), and even large kicks are unlikely to unbind the system. Indeed, BdHNe produce a new family of NS-BH binaries unaccounted for in current population synthesis analyses and, although they may be rare, the fact that nearly 100% remain bound implies that they may play an important role in the compact merger rate, important for gravitational waves that, in turn, can produce a new class of ultrashort GRBs. PMID- 26684108 TI - Black Hole Window into p-Wave Dark Matter Annihilation. AB - We present a new method to measure or constrain p-wave-suppressed cross sections for dark matter (DM) annihilations inside the steep density spikes induced by supermassive black holes. We demonstrate that the high DM densities, together with the increased velocity dispersion, within such spikes combine to make thermal p-wave annihilation cross sections potentially visible in gamma-ray observations of the Galactic center (GC). The resulting DM signal is a bright central point source with emission originating from DM annihilations in the absence of a detectable spatially extended signal from the halo. We define two simple reference theories of DM with a thermal p-wave annihilation cross section and establish new limits on the combined particle and astrophysical parameter space of these models, demonstrating that Fermi Large Area Telescope is currently sensitive to thermal p-wave DM over a wide range of possible scenarios for the DM distribution in the GC. PMID- 26684109 TI - Grand Canonical Ensembles, Multiparticle Wave Functions, Scattering Data, and Lattice Field Theories. AB - We show that information about scattering data of a quantum field theory can be obtained from studying the system at finite density and low temperatures. In particular we consider models formulated on the lattice that can be exactly dualized to theories of conserved charge fluxes on lattice links. Apart from eliminating the complex action problem at nonzero chemical potential MU, these dualizations allow for a particle world line interpretation of the dual fluxes from which one can extract data about the two-particle wave function. As an example we perform dual Monte Carlo simulations of the two-dimensional O(3) model at nonzero MU and finite volume, whose nonperturbative spectrum consists of a massive triplet of particles. At nonzero MU particles are induced in the system, which at sufficiently low temperature give rise to sectors of fixed particle number. We show that the scattering phase shifts can be obtained either from the critical chemical potential values separating the sectors or directly from the wave function in the two-particle sector. We find that both methods give excellent agreement with the exact result. We discuss the applicability and generality of the new approaches. PMID- 26684110 TI - Long-Lived Gluinos and Stable Axinos. AB - In this Letter we present a novel version of "long-lived" gluinos in supersymmetric models with the gluino lightest ordinary supersymmetric particle (LOSP) and the axino lightest supersymmetric particle. Within certain ranges of the axion decay constant f_{a}<1*10^{10} GeV, the gluino mass bounds are reduced to less than 1000 GeV. The best limits can be obtained by looking for decaying R hadrons in the detector where the gluino decays to a gluon and axino in the calorimeters. Supersymmetry (SUSY) models with a gluino LOSP can occur over a significant region of parameter space in either mirage mediation or general gauge mediated SUSY breaking models. The gluino LOSP is not constrained by cosmology, but in this scenario the axion or axino may be a good dark matter candidate. PMID- 26684107 TI - Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data. AB - The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on gamma-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in gamma rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ?100 GeV annihilating via quark and tau-lepton channels. PMID- 26684113 TI - Precision Mass Measurements of ^{129-131}Cd and Their Impact on Stellar Nucleosynthesis via the Rapid Neutron Capture Process. AB - Masses adjacent to the classical waiting-point nuclide ^{130}Cd have been measured by using the Penning-trap spectrometer ISOLTRAP at ISOLDE/CERN. We find a significant deviation of over 400 keV from earlier values evaluated by using nuclear beta-decay data. The new measurements show the reduction of the N=82 shell gap below the doubly magic ^{132}Sn. The nucleosynthesis associated with the ejected wind from type-II supernovae as well as from compact object binary mergers is studied, by using state-of-the-art hydrodynamic simulations. We find a consistent and direct impact of the newly measured masses on the calculated abundances in the A=128-132 region and a reduction of the uncertainties from the precision mass input data. PMID- 26684114 TI - Rotational Cooling of Trapped Polyatomic Molecules. AB - Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH_{3}F) by optically pumping the population of 16 M sublevels in the rotational states J=3, 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (~30 mK) and nearly pure state ensemble of about 10^{6} molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules. PMID- 26684111 TI - Test of Electric Charge Conservation with Borexino. AB - Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, tau>=6.6*10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit. PMID- 26684115 TI - Nuclear Recoil Effect in the Lamb Shift of Light Hydrogenlike Atoms. AB - We report high-precision calculations of the nuclear recoil effect to the Lamb shift of hydrogenlike atoms to the first order in the electron-nucleus mass ratio and to all orders in the nuclear binding strength parameter Zalpha. The results are in excellent agreement with the known terms of the Zalpha expansion and allow an accurate identification of the nonperturbative higher-order remainder. For hydrogen, the higher-order remainder was found to be much larger than anticipated. This result resolves the long-standing disagreement between the numerical all-order and analytical Zalpha-expansion approaches to the recoil effect and completely removes the second-largest theoretical uncertainty in the hydrogen Lamb shift of the 1S and 2S states. PMID- 26684116 TI - Three-Photon-Annihilation Contributions to Positronium Energies at Order malpha^{7}. AB - Positronium spectroscopy (n=1 hyperfine splitting, n=2 fine structure, and the 2S 1S interval) has reached a precision of order 1 MHz. Vigorous ongoing efforts to improve the experimental results motivate the calculation of the positronium energy levels at order malpha^{7}. In this Letter, we present the result for a complete class of such contributions-those involving virtual annihilation of positronium to three photons in an intermediate state. We find an energy shift of 2.6216(11)malpha^{7}/(npi)^{3}=11.5/n^{3} kHz for the spin-triplet S state with principal quantum number n. The corresponding energy shift for true muonium (the MU^{+}MU^{-} bound state) is 2.38/n^{3} MHz with an additional -5.33/n^{3} MHz coming from electronic vacuum polarization. PMID- 26684117 TI - Nonlinear Radiation Pressure Dynamics in an Optomechanical Crystal. AB - Utilizing a silicon nanobeam optomechanical crystal, we investigate the attractor diagram arising from the radiation pressure interaction between a localized optical cavity at lambda_{c}=1542 nm and a mechanical resonance at omega_{m}/2pi=3.72 GHz. At a temperature of T_{b}~10 K, highly nonlinear driving of mechanical motion is observed via continuous wave optical pumping. Introduction of a time-dependent (modulated) optical pump is used to steer the system towards an otherwise inaccessible dynamically stable attractor in which mechanical self-oscillation occurs for an optical pump red detuned from the cavity resonance. An analytical model incorporating thermo-optic effects due to optical absorption heating is developed and found to accurately predict the measured device behavior. PMID- 26684118 TI - Nanofriction in Cavity Quantum Electrodynamics. AB - The dynamics of cold trapped ions in a high-finesse resonator results from the interplay between the long-range Coulomb repulsion and the cavity-induced interactions. The latter are due to multiple scatterings of laser photons inside the cavity and become relevant when the laser pump is sufficiently strong to overcome photon decay. We study the stationary states of ions coupled with a mode of a standing-wave cavity as a function of the cavity and laser parameters, when the typical length scales of the two self-organizing processes, Coulomb crystallization and photon-mediated interactions, are incommensurate. The dynamics are frustrated and in specific limiting cases can be cast in terms of the Frenkel-Kontorova model, which reproduces features of friction in one dimension. We numerically recover the sliding and pinned phases. For strong cavity nonlinearities, they are in general separated by bistable regions where superlubric and stick-slip dynamics coexist. The cavity, moreover, acts as a thermal reservoir and can cool the chain vibrations to temperatures controlled by the cavity parameters and by the ions' phase. These features are imprinted in the radiation emitted by the cavity, which is readily measurable in state-of-the-art setups of cavity quantum electrodynamics. PMID- 26684119 TI - Asymmetric Acoustic Propagation of Wave Packets Via the Self-Demodulation Effect. AB - This Letter presents the experimental characterization of nonreciprocal elastic wave transmission in a single-mode elastic waveguide. This asymmetric system is obtained by coupling a selection layer with a conversion layer: the selection component is provided by a phononic crystal, while the conversion is achieved by a nonlinear self-demodulation effect in a 3D unconsolidated granular medium. A quantitative experimental study of this acoustic rectifier indicates a high rectifying ratio, up to 10^{6}, with wide band (10 kHz) and an audible effect. Moreover, this system allows for wave-packet rectification and extends the future applications of asymmetric systems. PMID- 26684120 TI - Hindered Energy Cascade in Highly Helical Isotropic Turbulence. AB - The conventional approach to the turbulent energy cascade, based on Richardson Kolmogorov phenomenology, ignores the topology of emerging vortices, which is related to the helicity of the turbulent flow. It is generally believed that helicity can play a significant role in turbulent systems, e.g., supporting the generation of large-scale magnetic fields, but its impact on the energy cascade to small scales has never been observed. We suggest, for the first time, a generalized phenomenology for isotropic turbulence with an arbitrary spectral distribution of the helicity. We discuss various scenarios of direct turbulent cascades with new helicity effect, which can be interpreted as a hindering of the spectral energy transfer. Therefore, the energy is accumulated and redistributed so that the efficiency of nonlinear interactions will be sufficient to provide a constant energy flux. We confirm our phenomenology by high Reynolds number numerical simulations based on a shell model of helical turbulence. The energy in our model is injected at a certain large scale only, whereas the source of helicity is distributed over all scales. In particular, we found that the helical bottleneck effect can appear in the inertial interval of the energy spectrum. PMID- 26684121 TI - Lifshitz Transition in the Double-Core Vortex in ^{3}He-B. AB - We study the spectrum of fermion states localized within the vortex core of a weak-coupling p-wave superfluid. The low energy spectrum consists of two anomalous branches that generate a large density of states at the locations of the half cores of the vortex. Fermi liquid interactions significantly stretch the vortex structure, which leads to a Lifshitz transition in the effective Fermi surface of the vortex core fermions. We apply the results to the rotational dynamics of vortices in superfluid ^{3}He-B and find an explanation for the observed slow mode. PMID- 26684122 TI - Generic Bistability in Creased Conical Surfaces. AB - The emerging field of mechanical metamaterials has sought inspiration in the ancient art of origami as archetypal deployable structures that carry geometric rigidity, exhibit exotic material properties, and are potentially scalable. A promising venue to introduce functionality consists in coupling the elasticity of the sheet and the kinematics of the folds. In this spirit, we introduce a scale free, analytical description of a very general class of snap-through, bistable patterns of creases naturally occurring at the vertices of real origami that can be used as building blocks to program and actuate the overall shape of the decorated sheet. These switches appear at the simplest possible level of creasing and admit straightforward experimental realizations. PMID- 26684123 TI - Complex Nanotwin Substructure of an Asymmetric Sigma9 Tilt Grain Boundary in a Silicon Polycrystal. AB - Grain boundaries in materials have substantial influences on device properties, for instance on mechanical stability or electronic minority carrier lifetime in multicrystalline silicon solar cells. This applies especially to asymmetric, less ordered or faceted interface portions. Here, we present the complex atomic interface structure of an asymmetric Sigma9 tilt grain boundary in silicon, observed by high resolution scanning transmission electron microscopy (HR-STEM) and explained by atomistic modeling and computer simulation. Structural optimization of interface models for the asymmetric Sigma9 and related symmetrical Sigma9 and Sigma3 tilt grain boundaries, by means of molecular statics simulations with empirical silicon potentials in combination with first principles calculations, results in a faceted asymmetric interface structure, whose grain-boundary energy is so low that it is likely to exist. The simulated local atomic structures match the observed HR-STEM images very well. PMID- 26684124 TI - Tailor the Functionalities of Metasurfaces Based on a Complete Phase Diagram. AB - Metasurfaces in a metal-insulator-metal configuration have been widely used in photonics, with applications ranging from perfect absorption to phase modulation, but why and when such structures can realize what functionalities are not yet fully understood. Here, we establish a complete phase diagram in which the optical properties of such systems are fully controlled by two simple parameters (i.e., the intrinsic and radiation losses), which are, in turn, dictated by the geometrical or material properties of the underlying structures. Such a phase diagram can greatly facilitate the design of appropriate metasurfaces with tailored functionalities demonstrated by our experiments and simulations in the terahertz regime. In particular, our experiments show that, through appropriate structural or material tuning, the device can be switched across the phase boundaries yielding dramatic changes in optical responses. Our discoveries lay a solid basis for realizing functional and tunable photonic devices with such structures. PMID- 26684125 TI - Pressure Effect on the Boson Peak in Deeply Cooled Confined Water: Evidence of a Liquid-Liquid Transition. AB - The boson peak in deeply cooled water confined in nanopores is studied to examine the liquid-liquid transition (LLT). Below ~180 K, the boson peaks at pressures P higher than ~3.5 kbar are evidently distinct from those at low pressures by higher mean frequencies and lower heights. Moreover, the higher-P boson peaks can be rescaled to a master curve while the lower-P boson peaks can be rescaled to a different one. These phenomena agree with the existence of two liquid phases with different densities and local structures and the associated LLT in the measured (P, T) region. In addition, the P dependence of the librational band also agrees with the above conclusion. PMID- 26684126 TI - Tuning the van der Waals Interaction of Graphene with Molecules via Doping. AB - We use scanning tunneling microscopy to visualize and thermal desorption spectroscopy to quantitatively measure that the binding of naphthalene molecules to graphene, a case of pure van der Waals interaction, strengthens with n and weakens with p doping of graphene. Density-functional theory calculations that include the van der Waals interaction in a seamless, ab initio way accurately reproduce the observed trend in binding energies. Based on a model calculation, we propose that the van der Waals interaction is modified by changing the spatial extent of graphene's pi orbitals via doping. PMID- 26684127 TI - Molecular Mechanism of Water Evaporation. AB - Evaporation is the process by which water changes from a liquid to a gas or vapor, and is a key step in Earth's water cycle. At the molecular level, evaporation requires breaking at least one very strong intermolecular bond between two water molecules at the interface. Despite the importance of this process the molecular mechanism by which an evaporating water molecule gains sufficient energy to escape from the surface has remained elusive. Here, we show, using molecular dynamics simulations at the water-air interface with polarizable classical force field models, that the high kinetic energy of the evaporated water molecule is enabled by a well-timed making and breaking of hydrogen bonds involving at least three water molecules at the interface, the recoil of which allows one of the molecules to escape. The evaporation of water is thus enabled by concerted, ultrafast hydrogen-bond dynamics of interfacial water, and follows one specific molecular pathway. PMID- 26684128 TI - One-Dimensional Quasicrystals from Incommensurate Charge Order. AB - Artificial quasicrystals are nowadays routinely manufactured, yet only two naturally occurring examples are known. We present a class of systems with the potential to be realized both artificially and in nature, in which the lowest energy state is a one-dimensional quasicrystal. These systems are based on incommensurately charge-ordered materials, in which the quasicrystalline phase competes with the formation of a regular array of discommensurations as a way of interpolating between incommensurate charge order at high temperatures and commensurate order at low temperatures. The nonlocal correlations characteristic of the quasicrystalline state emerge from a free-energy contribution localized in reciprocal space. We present a theoretical phase diagram showing that the required material properties for the appearance of such a ground state allow for one-dimensional quasicrystals to form in real materials. The result is a potentially wide class of one-dimensional quasicrystals. PMID- 26684129 TI - Universality of Plasmon Excitations in Dirac Semimetals. AB - We investigate the properties of the collective plasmon excitations in Dirac semimetals by using the methods of relativistic field theory. We find a strong and narrow plasmon excitation whose frequency is in the terahertz (THz) range which may be important for practical applications. The properties of the plasmon appear universal for all Dirac semimetals, due to the large degeneracy of the quasiparticles and the small Fermi velocity, v_{F}?c. This universality is closely analogous to the phenomenon of "dimensional transmutation" that is responsible for the emergence of dimensionful scales in relativistic field theories such as quantum chromodynamics. PMID- 26684130 TI - Quantum Quenches in Chern Insulators. AB - We explore the nonequilibrium response of Chern insulators. Focusing on the Haldane model, we study the dynamics induced by quantum quenches between topological and nontopological phases. A notable feature is that the Chern number, calculated for an infinite system, is unchanged under the dynamics following such a quench. However, in finite geometries, the initial and final Hamiltonians are distinguished by the presence or absence of edge modes. We study the edge excitations and describe their impact on the experimentally observable edge currents and magnetization. We show that, following a quantum quench, the edge currents relax towards new equilibrium values, and that there is light-cone spreading of the currents into the interior of the sample. PMID- 26684112 TI - Inclusive Production of the X(4140) State in pp[over -] Collisions at D0. AB - We present a study of the inclusive production of the X(4140) state with the decay to the J/psiphi final state in hadronic collisions. Based on 10.4 fb^{-1} of pp[over -] collision data collected by the D0 experiment at the Fermilab Tevatron collider, we report the first evidence for the prompt production of an X(4140) state and find the fraction of X(4140) events originating from b hadrons to be f_{b}=0.39+/-0.07(stat)+/-0.10(syst). The ratio of the nonprompt X(4140) production rate to the B_{s}^{0} yield in the same channel is R=0.19+/ 0.05(stat)+/-0.07(syst). The values of the mass M=4152.5+/-1.7(stat)_{ 5.4}^{+6.2}(syst) MeV and width Gamma=16.3+/-5.6(stat)+/-11.4(syst) MeV are consistent with previous measurements. PMID- 26684131 TI - Fidelity Susceptibility Perspective on the Kondo Effect and Impurity Quantum Phase Transitions. AB - The Kondo effect is a ubiquitous phenomenon appearing at low temperature in quantum confined systems coupled to a continuous bath. Efforts in understanding and controlling it have triggered important developments across several disciplines of condensed matter physics. A recurring pattern in these studies is that the suppression of the Kondo effect often results in intriguing physical phenomena such as impurity quantum phase transitions or non-Fermi-liquid behavior. We show that the fidelity susceptibility is a sensitive indicator for such phenomena because it quantifies the sensitivity of the system's state with respect to its coupling to the bath. We demonstrate the power of the fidelity susceptibility approach by using it to identify the crossover and quantum phase transitions in the one and two impurity Anderson models. The feasibility of measuring fidelity susceptibility in condensed matter as well as ultracold quantum gases experiments opens exciting new routes to diagnose the Kondo problem and impurity quantum phase transitions. PMID- 26684132 TI - Anomalous Crystal Symmetry Fractionalization on the Surface of Topological Crystalline Insulators. AB - The surface of a three-dimensional topological electron system often hosts symmetry-protected gapless surface states. With the effect of electron interactions, these surface states can be gapped out without symmetry breaking by a surface topological order, in which the anyon excitations carry anomalous symmetry fractionalization that cannot be realized in a genuine two-dimensional system. We show that for a mirror-symmetry-protected topological crystalline insulator with mirror Chern number n=4, its surface can be gapped out by an anomalous Z_{2} topological order, where all anyons carry mirror-symmetry fractionalization M^{2}=-1. The identification of such anomalous crystalline symmetry fractionalization implies that in a two-dimensional Z_{2} spin liquid, the vison excitation cannot carry M^{2}=-1 if the spinon carries M^{2}=-1 or a half-integer spin. PMID- 26684133 TI - Surface Effects on the Mott-Hubbard Transition in Archetypal V{2}O{3}. AB - We present an experimental and theoretical study exploring surface effects on the evolution of the metal-insulator transition in the model Mott-Hubbard compound Cr doped V{2}O{3}. We find a microscopic domain formation that is clearly affected by the surface crystallographic orientation. Using scanning photoelectron microscopy and x-ray diffraction, we find that surface defects act as nucleation centers for the formation of domains at the temperature-induced isostructural transition and favor the formation of microscopic metallic regions. A density functional theory plus dynamical mean-field theory study of different surface terminations shows that the surface reconstruction with excess vanadyl cations leads to doped, and hence more metallic, surface states, which explains our experimental observations. PMID- 26684134 TI - Landau Levels in Strained Optical Lattices. AB - We propose a hexagonal optical lattice system with spatial variations in the hopping matrix elements. Just like in the valley Hall effect in strained graphene, for atoms near the Dirac points the variations in the hopping matrix elements can be described by a pseudomagnetic field and result in the formation of Landau levels. We show that the pseudomagnetic field leads to measurable experimental signatures in momentum resolved Bragg spectroscopy, Bloch oscillations, cyclotron motion, and quantization of in situ densities. Our proposal can be realized by a slight modification of existing experiments. In contrast to previous methods, pseudomagnetic fields are realized in a completely static system avoiding common heating effects and therefore opening the door to studying interaction effects in Landau levels with cold atoms. PMID- 26684135 TI - Quantized Evolution of the Plasmonic Response in a Stretched Nanorod. AB - Quantum aspects, such as electron tunneling between closely separated metallic nanoparticles, are crucial for understanding the plasmonic response of nanoscale systems. We explore quantum effects on the response of the conductively coupled metallic nanoparticle dimer. This is realized by stretching a nanorod, which leads to the formation of a narrowing atomic contact between the two nanorod ends. Based on first-principles time-dependent density-functional-theory calculations, we find a discontinuous evolution of the plasmonic response as the nanorod is stretched. This is especially pronounced for the intensity of the main charge-transfer plasmon mode. We show the correlation between the observed discontinuities and the discrete nature of the conduction channels supported by the formed atomic-sized junction. PMID- 26684136 TI - Proximity-Induced pi Josephson Junctions in Topological Insulators and Kramers Pairs of Majorana Fermions. AB - We study two microscopic models of topological insulators in contact with an s wave superconductor. In the first model the superconductor and the topological insulator are tunnel coupled via a layer of randomly distributed scalar and of randomly oriented spin impurities. Here, we demonstrate that spin-flip tunneling dominates over the spin-conserving one. In the second model the tunnel coupling is realized by a spatially nonuniform array of single-level quantum dots with randomly oriented spins. We find that the tunnel region forms a pi junction where the effective order parameter changes sign. Because of the random spin orientation, effectively both models exhibit time-reversal symmetry. The proposed pi junctions support topological superconductivity without magnetic fields and can be used to generate and manipulate Kramers pairs of Majorana fermions by gates. PMID- 26684137 TI - Mapping the Electronic Structure of Each Ingredient Oxide Layer of High-T?{c} Cuprate Superconductor Bi{2}Sr{2}CaCu{2}O{8+delta}. AB - Understanding the mechanism of high transition temperature (T{c}) superconductivity in cuprates has been hindered by the apparent complexity of their multilayered crystal structure. Using a cryogenic scanning tunneling microscopy (STM), we report on layer-by-layer probing of the electronic structures of all ingredient planes (BiO, SrO, CuO{2}) of Bi{2}Sr{2}CaCu_2}O{8+delta} superconductor prepared by argon-ion bombardment and annealing technique. We show that the well-known pseudogap (PG) feature observed by STM is inherently a property of the BiO planes and thus irrelevant directly to Cooper pairing. The SrO planes exhibit an unexpected van Hove singularity near the Fermi level, while the CuO{2} planes are exclusively characterized by a smaller gap inside the PG. The small gap becomes invisible near T{c}, which we identify as the superconducting gap. The above results constitute severe constraints on any microscopic model for high T{c} superconductivity in cuprates. PMID- 26684138 TI - Spin Superfluidity and Long-Range Transport in Thin-Film Ferromagnets. AB - In ferromagnets, magnons may condense into a single quantum state. Analogous to superconductors, this quantum state may support transport without dissipation. Recent works suggest that longitudinal spin transport through a thin-film ferromagnet is an example of spin superfluidity. Although intriguing, this tantalizing picture ignores long-range dipole interactions; here, we demonstrate that such interactions dramatically affect spin transport. In single-film ferromagnets, "spin superfluidity" only exists at length scales (a few hundred nanometers in yttrium iron garnet) somewhat larger than the exchange length. Over longer distances, dipolar interactions destroy spin superfluidity. Nevertheless, we predict the reemergence of spin superfluidity in trilayer ferromagnet-normal metal-ferromagnet films that are ~1 MUm in size. Such systems also exhibit other types of long-range spin transport in samples that are several micrometers in size. PMID- 26684139 TI - Origin of Perpendicular Magnetic Anisotropy and Large Orbital Moment in Fe Atoms on MgO. AB - We report on the magnetic properties of individual Fe atoms deposited on MgO(100) thin films probed by x-ray magnetic circular dichroism and scanning tunneling spectroscopy. We show that the Fe atoms have strong perpendicular magnetic anisotropy with a zero-field splitting of 14.0+/-0.3 meV/atom. This is a factor of 10 larger than the interface anisotropy of epitaxial Fe layers on MgO and the largest value reported for Fe atoms adsorbed on surfaces. The interplay between the ligand field at the O adsorption sites and spin-orbit coupling is analyzed by density functional theory and multiplet calculations, providing a comprehensive model of the magnetic properties of Fe atoms in a low-symmetry bonding environment. PMID- 26684140 TI - Realizing All so(N)_{1} Quantum Criticalities in Symmetry Protected Cluster Models. AB - We show that all so(N)_{1} universality class quantum criticalities emerge when one-dimensional generalized cluster models are perturbed with Ising or Zeeman terms. Each critical point is described by a low-energy theory of N linearly dispersing fermions, whose spectrum we show to precisely match the prediction by so(N)_{1} conformal field theory. Furthermore, by an explicit construction we show that all the cluster models are dual to nonlocally coupled transverse field Ising chains, with the universality of the so(N)_{1} criticality manifesting itself as N of these chains becoming critical. This duality also reveals that the symmetry protection of cluster models arises from the underlying Ising symmetries and it enables the identification of local representations for the primary fields of the so(N)_{1} conformal field theories. For the simplest and experimentally most realistic case that corresponds to the original one-dimensional cluster model with local three-spin interactions, our results show that the su(2)_{2}?so(3)_{1} Wess-Zumino-Witten model can emerge in a local, translationally invariant, and Jordan-Wigner solvable spin-1/2 model. PMID- 26684141 TI - Dynamic Response of a Single Interface in a Biocomposite Structure. AB - Biological composite materials are known to be tough, stiff, stable, viscoelastic bodies, that can creep, recover, absorb energy, and filter vibrations. Their multifunctionality is associated with their architectures, which often consist of mineral units surrounded by organic interfaces that play a key role in the performance of the entire composite. However, the confinement and small dimensions of these organic interfaces pose a challenge in measuring their physical properties by direct methods. We propose an indirect, experimental analytical framework by which to probe the elastic and viscoelastic behavior of an individual interface. We demonstrate this framework on thin organic interfaces in the shell Pinna nobilis, and discuss its possible uses in various other micro- and nanoscale composite systems. PMID- 26684143 TI - Fluctuation Relations of Fitness and Information in Population Dynamics. AB - Phenotype switching with and without sensing environment is a common strategy of organisms to survive in a fluctuating environment. Understanding the evolutionary advantages of switching and sensing requires a quantitative evaluation of their fitness gain and its fluctuation together with the conditions for the switching and sensing strategies being adapted to a given environment. In this work, by using a pathwise formulation of the population dynamics, we show that the optimal switching strategy is characterized by a consistency condition for time-forward and backward path probabilities. The formulation also clarifies the underlying information-theoretic aspect of selection as a passive information compression. The loss of fitness by a suboptimal strategy is also shown to satisfy a fluctuation relation, which provides us with the information on how environmental fluctuation impacts the advantages of the optimal strategy. These results are naturally extended to the situation that organisms can use an environmental signal by actively sensing the environment. The fluctuation relations of the fitness gain by sensing are derived in which the multivariate mutual information among the phenotype, the environment, and the signal plays the role to quantify the relevant information in the signal for the fitness gain. PMID- 26684142 TI - Hydrodynamics Versus Intracellular Coupling in the Synchronization of Eukaryotic Flagella. AB - The influence of hydrodynamic forces on eukaryotic flagella synchronization is investigated by triggering phase locking between a controlled external flow and the flagella of C. reinhardtii. Hydrodynamic forces required for synchronization are over an order of magnitude larger than hydrodynamic forces experienced in physiological conditions. Our results suggest that synchronization is due instead to coupling through cell internal fibers connecting the flagella. This conclusion is confirmed by observations of the vfl3 mutant, with impaired mechanical connection between the flagella. PMID- 26684144 TI - Simultaneous Scanning Ion Conductance Microscopy and Atomic Force Microscopy with Microchanneled Cantilevers. AB - We combined scanning ion conductance microscopy (SICM) and atomic force microscopy (AFM) into a single tool using AFM cantilevers with an embedded microchannel flowing into the nanosized aperture at the apex of the hollow pyramid. An electrode was positioned in the AFM fluidic circuit connected to a second electrode in the bath. We could thus simultaneously measure the ionic current and the cantilever bending (in optical beam deflection mode). First, we quantitatively compared the SICM and AFM contact points on the approach curves. Second, we estimated where the probe in SICM mode touches the sample during scanning on a calibration grid and applied the finding to image a network of neurites on a Petri dish. Finally, we assessed the feasibility of a double controller using both the ionic current and the deflection as input signals of the piezofeedback. The experimental data were rationalized in the framework of finite elements simulations. PMID- 26684145 TI - Experimental Validation of a Nonextensive Scaling Law in Confined Granular Media. AB - In this Letter, we address the relationship between the statistical fluctuations of grain displacements for a full quasistatic plane shear experiment, and the corresponding anomalous diffusion exponent alpha. We experimentally validate a particular case of the Tsallis-Bukman scaling law, alpha=2/(3-q), where q is obtained by fitting the probability density function (PDF) of the displacement fluctuations with a q-Gaussian distribution, and the diffusion exponent is measured independently during the experiment. Applying an original technique, we are able to evince a transition from an anomalous diffusion regime to a Brownian behavior as a function of the length of the strain window used to calculate the displacements of the grains. The outstanding conformity of fitting curves to a massive amount of experimental data shows a clear broadening of the fluctuation PDFs as the length of the strain window decreases, and an increment in the value of the diffusion exponent-anomalous diffusion. Regardless of the size of the strain window considered in the measurements, we show that the Tsallis-Bukman scaling law remains valid, which is the first experimental verification of this relationship for a classical system at different diffusion regimes. We also note that the spatial correlations show marked similarities to the turbulence in fluids, a promising indication that this type of analysis can be used to explore the origins of the macroscopic friction in confined granular materials. PMID- 26684146 TI - Comment on "Surface Plasmons and Nonlocality: A Simple Model". AB - A Comment on the Letter by Y. Luo, A. I. Fernandez-Dominguez, A. Wiener, S. A. Maier, and J. B. Pendry, Phys. Rev. Lett. 111, 093901 (2013).. The authors of the Letter offer a Reply. PMID- 26684147 TI - Luo et al. Reply. PMID- 26684148 TI - Treatment of diffuse large B-cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS-penetrating R-IDARAM chemotherapy. AB - Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12.5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly. PMID- 26684150 TI - AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM. AB - OBJECTIVE: Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. METHODS: This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 MUg/day rhPTH(1-84), escalated to 75 and then to 100 MUg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was >=50% reduction in oral calcium (or <=500 mg/day) and active vitamin D (or calcitriol <=0.25 MUg/day or alfacalcidol <=0.50 MUg/day) with normocalcemia. RESULTS: Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naive) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium * phosphate (Ca * P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. CONCLUSION: This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies. PMID- 26684149 TI - DUAL-ENERGY X-RAY ABSORPTIOMETRY AND CALCULATED FRAX RISK SCORES MAY UNDERESTIMATE OSTEOPOROTIC FRACTURE RISK IN VITAMIN D-DEFICIENT VETERANS WITH HIV INFECTION. AB - OBJECTIVE: We evaluated the utility of the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency. METHODS: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the WHO FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures. RESULTS: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant. CONCLUSION: We found a high prevalence of subclinical vertebral fractures among vitamin D deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population. PMID- 26684151 TI - HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH NONFUNCTIONING PITUITARY ADENOMAS UNDERGOING POSTOPERATIVE RADIATION THERAPY: A CASE-CONTROL STUDY. AB - OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) can be associated with significant morbidity including a compromised quality of life (QoL). Radiotherapy (RT) is listed as one of the contributing factors to QoL impairment in these patients, however the evidence supporting this association is scarce and conflicting. Here we evaluate health-related QoL (HRQoL) impairment in patients with NFPA and to what extent this is due to RT. METHODS: HRQoL was evaluated with the short form-36 questionnaire (SF-36), which explores 8 domains pertaining physical, emotional, and mental well being. We assessed 50 patients with NFPA subjected to RT after pituitary surgery, and their results were compared to those from 127 subjects who had undergone surgery but not RT. Both groups were matched for age, sex, and metabolic and cardiovascular comorbidities. The SF-36 was applied a median of 72 months after RT in the group of cases and 78 months after the last surgical procedure in the control group. RESULTS: Both groups scored equally low in the 8 areas explored by the survey. In a multiple linear regression model, age was significantly associated with worse physical health scores, whereas female sex was associated with worse general health perception and lower emotional role and physical role scores. The presence of a visual field defect was significantly associated with a worse social role functioning score. CONCLUSION: QoL in patients with NFPAs is significantly compromised in most scales evaluated by the SF-36 survey. However, RT itself does not affect QoL. PMID- 26684152 TI - BONE MINERAL DENSITY IN PATIENTS WITH ADDISON DISEASE ON REPLACEMENT THERAPY WITH PREDNISOLONE. AB - OBJECTIVE: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement. METHODS: Forty-one consecutive patients (31 males, age [mean +/- SD] 50.9 +/- 13.0 years), receiving prednisolone (hydrocortisone equivalent [HCE] 13.0 +/- 3.0 mg/m(2)) for 104 +/- 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677). RESULTS: Among males, BMD Z scores (mean [95% confidence interval {CI}]) at lumbar spine (-0.42 [-0.80, 0.04]), femoral neck (-0.50 [-0.95, -0.06]) and total hip (-0.58 [-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score <=-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD. CONCLUSIONS: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites. PMID- 26684153 TI - DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS INCREASES CENTRAL BODY FAT ACCUMULATION IN MALES AFFECTED BY DIABETES MELLITUS AND LATE-ONSET HYPOGONADISM. AB - OBJECTIVE: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary adrenal (HPA) axis dysregulation on body composition in men affected by DM associated late-onset hypogonadism (LOH). METHODS: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered. RESULTS: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 +/- 0.27 ng/mL versus 2.31 +/- 0.26 ng/mL; P = .003) and free (39.5 +/- 6.44 pg/mL versus 46.8 +/- 7.23 pg/mL; P = .005) (median, 38.7 [interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 [interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized beta = 10.988 [P<.001]; beta = 1.156 [P<.001]; beta = -7.675 [P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH. CONCLUSION: Dysregulation of the HPA axis in LOH associated DM seems to be involved in abdominal fat accumulation. PMID- 26684154 TI - IS BIOCHEMICAL ASSESSMENT OF PHEOCHROMOCYTOMA NECESSARY IN ADRENAL INCIDENTALOMAS WITH MAGNETIC RESONANCE IMAGING FEATURES NOT SUGGESTIVE OF PHEOCHROMOCYTOMA? AB - OBJECTIVE: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial. METHODS: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines. RESULTS: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences. CONCLUSION: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results. PMID- 26684155 TI - Sexual Compulsivity and Sexual Sensation Seeking: A Preliminary Approach Among Male Sex Workers Compared to Gay Men in Spain. AB - This study aims to explore sexual compulsivity (SC) and sexual sensation seeking (SSS) in male sex workers (MSWs) compared to a group of non-MSW gay men. A total of 60 MSWs and 63 gay men answered the SC Scale and the SSS Scale. The total scales' mean score was slightly higher in the MSW population. Still, statistical differences were observed in only two SSS items. In spite of the absence of statistical significance, MSWs presented more sexual behavior interferences on their lives and higher failure to control sexual impulses. Future interventions among MSWs should focus on sexual self-control and impulsivity. PMID- 26684156 TI - Predicting Osteopenia and Osteoporosis with a Simple Test: A Preliminary Work. AB - Objective: The occurrence of osteopenia and osteoporosis is a major problem of ageing. For assessing the severity of bone loss, bone mineral density (BMD) measurement is the gold standard. Because of the limitations of BMD, use of simpler serum-based tests to classify osteoporosis/osteopenia patients is gaining interest. In this preliminary work, we aimed to discriminate between healthy individuals and osteoporosis/osteopenia patients through a simple serum-based equation. Methods: In this study, blood from 84 elderly persons were collected and levels of vitamin D, calcium (Ca), phosphorus (P), copper (Cu) and strontium (Sr) were analysed. Additionally, all persons included in the study underwent BMD measurement. Results: Bone mineral density showed that 28 persons had osteoporosis, 28 persons suffered from osteopenia and 28 persons were classified as normal. Using the above-mentioned parameters and major determinants of bone loss disorders, ie age and body mass index (BMI), we suggested various equations. The "Osteo-Pars" equation that is derived from the formula [(Sr * Age)/BMI] showed the best diagnostic accuracy in receiver operating characteristic analysis. Conclusion: The suggested equation is a simple model that obtains reasonable results in discriminating healthy individuals from patients with osteopenia/osteoporosis. More study is needed to reach an exact, conclusive statement about the potential clinical application of this equation in the assessment of bone loss severity. PMID- 26684157 TI - Nutritional Knowledge, Attitude and Practice among Patients with Type 2 Diabetes in North Central Health Authority in Trinidad and Tobago. AB - Objectives: To assess knowledge, attitude and practice in relation to their disease among patients with Type 2 diabetes mellitus in one regional health district in Trinidad and Tobago and to compare these attributes between patients receiving/not receiving nutrition counselling. Methods: A cohort of 122 patients with diabetes was selected on site at their respective public clinics via quota sampling and surveyed using a structured questionnaire. Results: Mean knowledge score was 5.4 (SD = 0.985). Mean attitude and practice scores were significant between those who received and did not receive counselling (p = 0.033 and < 0.001, respectively). Patients receiving nutrition counselling were more likely than those not receiving counselling to not drink soft drinks (p < 0.001), consume fast foods (p < 0.001) and drink alcohol (p = 0.003) but were equally likely to drink at least eight glasses of water daily. Additionally, patients receiving and those not receiving counselling were equally likely to agree with the attitude statements given. There was a statistically significant interaction between the effects of gender and age group on knowledge score, F = 2.631, p = 0.039. Nutrition counselling was a statistically significant predictor of knowledge score (B = 0.444, standard error = 0.192, p = 0.023). Conclusions: Patients receiving nutrition counselling were more knowledgeable about diabetes than those not receiving such counselling, and had a more positive outlook as to what it would take on the part of the patient and clinicians to manage the disease effectively. PMID- 26684158 TI - Clinical Profile of Familial Mediterranean Fever in a Paediatric Population in Eastern Turkey. AB - Objective: Clinical and genetic findings of familial Mediterranean fever (FMF) may vary in different populations. Environmental factors may also affect phenotypic features of FMF. In this study, we investigated demographic, clinical and mutational features of FMF patients treated in a single reference hospital in Turkey. Subjects and Methods: One hundred and ninety-seven patients were included. The 11 mutations most frequently seen in FMF were investigated in these patients. Patients were assessed as homozygous, heterozygous, compound heterozygous or non-mutation bearing. Clinical and laboratory examinations in the attack and attack-free periods were recorded. A disease severity score was calculated for each patient. Results: One hundred patients were female and 97 male. The most commonly seen mutations in our region was M694V (51.7%). The most frequent clinical findings in our patients was gastric pain (90.1%), followed by fever (82.2%). The highest disease severity score was determined in patients with homozygous M694V. Sedimentation values were significantly high in patients with homozygous M694V mutation, while no statistically significant difference was determined among other acute phase reactants and haemoglobin and leukocyte values. Conclusion: Changes in acute phase reactants in attack and attack-free periods are used as diagnostic tools in FMF. Severity and frequency of attacks are clearly correlated with mutations. However, the fact that the clinical course can differ even in individuals with mutations reveals the importance of environmental factors. PMID- 26684163 TI - Antimicrobial Activity of the Essential Oil from the Leaves and Seeds of Coriandrum sativum toward Food-borne Pathogens. AB - The increasing incidence of drug-resistant pathogens and toxicity of existing antibacterial compounds has drawn attention toward the antimicrobial activity of natural products. The purpose of this study is to evaluate the antimicrobial activity of the essential oil of the leaves and seeds of Coriandrum sativum. The five strains of bacteria comprising Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica, Salmonella enterica and Vibrio cholerae were used for the antibacterial tests. In this study, antimicrobial effects of the essential oil from the leaves and seeds of Coriandrum sativum are evaluated by determining the minimum inhibitory concentration (MIC), the inhibition zone and minimum bactericidal concentration (MBC). The essential oil from Coriandrum sativum was extracted by steam distillation. The results indicate that the antimicrobial activities against the five pathogens were in the range of 2.5- 320 ug/mL. Increase in essential oil concentration caused significant increase in inhibitory feature. The essential oil of the leaves and seeds of Coriandrum sativum showed antimicrobial activity against the food-borne pathogenic bacteria. Thus, its oil can be used as an alternative to synthetic food preservative without toxic effects. Also, it can be used in biotechnological fields as ingredients in antibiotics and the pharmaceutical industry. These results suggest that the essential oil of C sativum leaves and seeds may have potential use in pharmaceutical and food industries for preservatives or antimicrobial agents. PMID- 26684161 TI - Aetiology of Paediatric End-stage Renal Failure in Jordan: A Multicentre Study. AB - Objective: The purpose of this study was to find out the aetiology of end-stage renal failure (ESRF) in children in Jordan. Subjects and Methods: This was a multicentre retrospective study at five participating hospitals. Data collection included medical record review for age, gender, aetiology of ESRF, modality of renal replacement therapy (RRT) and outcome. End-stage renal failure was defined as estimated glomerular filtration rate < 15 mL/min/1.73m2. Results: There were 275 children with ESRF: 131males and 144 females. The most common causes of ESRF in children were congenital anomalies of the kidney and urinary tract (CAKUT), 45.8%, heredofamilial disorders, 23.2% and glomerulopathies, 26.2%. Neurogenic bladder, reflux nephropathy and posterior urethral valve accounted for 16.8%, 12.7% and 4.0%, respectively. Amongst the heredofamilial disorders, primary oxalosis and cystic disease accounted for 8.0% and 7.2% of the aetiologies of ESRF, respectively. Focal segmental glomerulosclerosis was the most common histological type amongst the glomerulopathies (10.2%), followed by mesangiocapillary glomerulonephritis (4.7%) and chronic glomerulonephritis (3.0%). The aetiology was unknown in 4% of the cases. The modality of dialysis included isolated peritoneal dialysis (PD) in 30.9%, isolated haemodialysis (HD) in 49.1%, alternating peritoneal and haemodialysis in 9.1%, transplanted in 8.7% and conservative treatment in 1.8%. Death occurred in 57.3% of PD patients versus 34.4% in HD patients. Conclusions: This is the first report on the aetiology of ESRF in children in Jordan. The most common aetiologies of ESRF were CAKUT 45.8%, heredofamilial disorders 23.2% and glomerulopathies 22.9%. PMID- 26684164 TI - Combination Therapy in Pulmonary Arterial Hypertension: Single Centre Long-term Experience. AB - Background: Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vascular bed and causes right heart failure and death. Combination therapy which targets three different pathways is necessary due to the progressive nature of the disease. In patients with PAH, there are two approaches in combination therapy: "first-line up-front" and "sequential add-on" treatment. In "firstline up-front" treatment, patients receive double or triple drug therapy from the start. In the "sequential add-on" approach, a single drug is initially started and then according to the patient's requirements, a second or third drug is added. There is insufficient evidence about the efficiency and safety of treatment approaches. In this study, we aimed to evaluate the treatment approach in patients with PAH at a tertiary centre. Methods: Pulmonary arterial hypertension was diagnosed according to clinical, echocardiographic and right heart catheterization findings. The patients received bosentan, sildenafil and iloprost treatment in accordance with guidelines recommendations. Clinical worsening in patients was defined as death, requirement of hospitalization for PAH, a 15% decline in the six-minute walk test (6MWT) distance, deterioration in functional capacity, and symptoms and findings of right heart failure. Results: At the end of the follow-up period, clinical and echocardiographic findings, brain natriuretic peptide (BNP) levels and oxygen saturation were similar between patients who completed the study with monotherapy and with combination therapy. The follow-up period was significantly longer in patients who required combination treatment. Two patients (6.9%) died and four patients (13.8%) were hospitalized due to recurrent symptoms and findings of right heart failure. At the end of follow-up, 10 patients (34.5%) completed the study with a single drug, 15 patients (51.7%) with two drugs and four patients (13.8%) with three drugs. Conclusion: In this study, combination therapy was given to patients as "sequential add-on therapy". At the end of the follow-up period, monotherapy was sufficient in 34.5% of patients of the study group and in eight patients, sildenafil or prostaglandin analogues were added; a total of 15 patients (48.4%) completed the study under dual therapy. Four patients (12.9%) received combination therapy with three drugs. PMID- 26684166 TI - Diabetes mellitus in patients with pulmonary tuberculosis in an aging population in Shanghai, China: Prevalence, clinical characteristics and outcomes. AB - AIMS: To determine the prevalence of diabetes mellitus among pulmonary tuberculosis patients and the difference of clinical characteristics and outcomes between pulmonary tuberculosis patients with and without diabetes mellitus in an aging population in Shanghai, China. METHODS: This is a retrospective population based study. 201 newly diagnosed pulmonary tuberculosis patients in Changning District, Shanghai during 2007-2008 were included. Clinical characteristics and outcomes were collected. Determination of diabetes mellitus was based on the medical records before pulmonary tuberculosis was diagnosed. RESULTS: The prevalence of diabetes mellitus among pulmonary tuberculosis patients was 19.9% (40/201). Pulmonary tuberculosis patients with diabetes mellitus were more likely to be old (>=50, OR=5.23, 95% CI=2.07-13.25), to have pulmonary cavities (OR=3.02, 95% CI=1.31-6.98), to be sputum smear positive (OR=2.90, 95% CI=1.12 7.51), and to have extension of anti-tuberculosis treatment duration (OR=2.68, 95% CI 1.17-6.14). Besides, they had a higher 2nd month sputum smear positive proportion (OR=2.97, 95% CI 1.22-7.22) and a higher 5-year recurrence rate (OR=5.87, 95% CI 1.26-27.40). CONCLUSIONS: High prevalence, severe clinical characteristics and poor outcomes of pulmonary tuberculosis patients with diabetes mellitus highlight the necessity of early bi-directional screening and co-management of these two diseases in Shanghai, China. PMID- 26684167 TI - Diabetes is associated with increased risks of low lean mass and slow gait speed when peripheral artery disease is present. AB - AIMS: The aim of the current study was to evaluate the independent relationship of diabetes and PAD with lean mass and gait speed. METHODS: This was a cross sectional study of the U.S. population in 1999 through 2004, including 4769 participants aged >=40 years of the National Health and Nutrition Examination Survey 1999-2004. Appendicular lean mass divided by body mass index (ALMBMI) and gait speed were analyzed. Low lean mass was defined as ALMBMI <0.512 in women and <0.789 in men, whereas mobility impairment was defined as gait speed <0.8m/s. RESULTS: In the fully adjusted model, participants with both diabetes and PAD had a higher odds of low lean mass (OR=2.21; 95% CI: 1.07-4.57) and mobility impairment (OR=4.8; 95% CI: 1.93-11.97) when compared with participants with neither diabetes nor PAD. No significant association of "with diabetes without PAD" or "with PAD without diabetes" with low lean mass or mobility impairment was observed. Participants with diabetes and PAD had significantly lower ALMBMI and gait speed when compared with all other participants. CONCLUSIONS: People with both diabetes and PAD had a higher likelihood of low lean mass and mobility impairment; such association was not observed in people with either diabetes or PAD alone. PMID- 26684168 TI - Diabetes mellitus and the risk of gallbladder disease: A systematic review and meta-analysis of prospective studies. AB - BACKGROUND: Diabetes has been hypothesized to increase the risk of gallbladder disease based on the observation that obesity and insulin resistance are associated with gallbladder disease. Although several studies have investigated the association between a diabetes diagnosis and risk of gallbladder disease, the results have not been entirely consistent. For this reason we conducted a systematic review and meta-analysis of the available cohort studies. MATERIALS AND METHODS: We searched the PubMed and Embase databases for studies of diabetes and gallbladder disease (defined as gallstones, cholecystectomy, or cholecystitis) up to January 9th 2015. Prospective studies were included if they reported relative risk estimates and 95% confidence intervals of gallbladder disease associated with a diabetes diagnosis. Summary relative risks were estimated by use of a random effects model. RESULTS: We identified 10 prospective studies that could be included in the meta-analysis which included 223,651 cases among 7,365,198 participants. The summary RR for diabetes patients was 1.56 (95% CI: 1.26-1.93, I(2)=99.4%, pheterogeneity<0.0001). The results persisted when stratified by gender, and in most subgroup analyses and there was no heterogeneity among studies with more than 10 years duration of follow-up. There was no evidence of publication bias. CONCLUSIONS: Our analysis provides further support for an increased risk of gallbladder disease among diabetes patients. PMID- 26684169 TI - Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies. AB - BACKGROUND: The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. METHODS: This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic. RESULTS: Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p<0.001), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p<0.00001), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p<0.00001), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p<0.00001). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size. DISCUSSION: Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings. PMID- 26684170 TI - The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes. AB - AIMS: The Haptoglobin (HP) 2-2 genotype increases cardiovascular diabetes complication incidence. In type 1 diabetes, HP 2-2 also predicts declining kidney function and end-stage renal disease. We investigated whether HP 2-2 predisposes to cardio-renal mortality, while considering other causes of death as competing risks. METHODS: Individuals with type 1 diabetes and HP data available (n=486; mean baseline age, 27 and duration, 19 years) were selected for study. Vital status was assessed as of 8/31/2014. The underlying cause of death was determined and classified based on standardized procedures. RESULTS: During 25 years of follow-up, 79 (16.3%) cardio-renal deaths and 43 (8.8%) deaths related to other causes occurred. Although total mortality did not differ by HP (25.4% with HP 1 versus 24.6% with HP 2-2, p=0.84), a greater proportion of HP 2-2 carriers exhibited a cardio-renal death (19.0 versus 14.2, p=0.05). In time-to-event analyses, HP 2-2 was associated with a statistically significant increase of the sub-distribution hazard ratio for cardio-renal mortality (HR=1.64, p=0.03), although this effect was somewhat attenuated after multivariable adjustment (HR=1.58, p=0.05). CONCLUSIONS: Our results suggest that in addition to predicting the incidence of cardio-renal complications, HP 2-2 also increases susceptibility for cardio-renal mortality in type 1 diabetes. These findings require validation in other cohorts. PMID- 26684171 TI - Understanding clusters of risk factors across different environmental and social contexts for the prediction of injuries among Canadian youth. AB - BACKGROUND: Among Canadian youth, injury is the most common reason for presentation to the emergency department. Youth who commonly engage in multiple risk-taking behaviours are at greater risk for injury, but is it unknown if this phenomenon is more pronounced in different contexts. We aimed to study relationships between risk-taking behaviours and injury, and variations in such relationships between different environmental and social contexts, among youth in Canada. METHODS: Risk-taking behaviour and injury outcome data were collected from grade 9 to 10 students using the 2009-2010 (Cycle 6) of the Health Behaviour in School-Aged Children Survey (n=10,429). Principal components analysis was used to identify clusters of risk-taking behaviours. Within each identified cluster, the degree of risk-taking was categorized into quartiles from lowest to highest engagement in the behaviours. Risk ratios with 95% confidence intervals were calculated to determine the association between the risk of any injury and the degree of risk-taking behaviour specific to the cluster. Clusters were then examined across home, school, neighbourhood and sport contexts. RESULTS: Four clusters of risk-taking behaviour were identified which were labelled as "gateway substance use", "hard drugs and weapons", "overt risk-taking", and "physical activity". Each cluster was related to injury occurrence in a graded fashion. Clusters of risk behaviour were most strongly associated with injuries sustained in neighbourhood settings, and expectedly, increasing physical activity behaviours were associated with increased risk of sport injuries and injuries occurring at school. CONCLUSIONS: This study furthers understanding of clustered risk-taking phenomena that put youth at increasing levels of injury risk. Higher risks for injury and associated gradients were observed in less structured contexts such as neighbourhoods. In contrast, clustered physical activity behaviours were most related to school injury or sport injury and were more likely to be sustained in a supervised context. Understanding the clustered and cumulative nature of risk-behaviours, and how these vary by environmental and social context, helps to explain potential mechanisms of injury as well as modifiable factors that may be important avenues for intervention. PMID- 26684172 TI - The anterolateral supra-fibular-head approach for plating posterolateral tibial plateau fractures: A novel surgical technique. AB - OBJECTIVE: The posterolateral (PL) tibial plateau quadrant is laterally covered by the fibular head and posteriorly covered by a mass of muscle ligament and important neurovascular structures. There are several limitations in exposing and fixing the PL tibial plateau fractures using a posterior approach. The aim of this study is to present a novel anterolateral supra-fibular-head approach for plating PL tibial plateau fractures. METHODS: Five fresh and ten preserved knee specimens were dissected to measure the following parameters:1) the vertical distance from the apex of the fibular head to the lateral plateau surface, 2) the transverse distance between the PL platform and fibula collateral ligament (FCL), and 3) the tension of the FCL in different knee flexion positions. Clinically, isolated PL quadrant tibial plateau fractures were treated via an anterolateral supra-fibular-head approach and lateral rafting plate fixation. The outcome of the patients was assessed after a short to medium follow-up period. RESULTS: The distance from the apex of the fibular head to the lateral condylar surface was 12.2 +/- 1.6 mm on average. With the knee extended and the FCL tensioned, the transverse distance between the PL platform and the FCL was 6.7 +/- 1.1 mm. With the knee flexed to 60 degrees and the FCL was in the most relaxed position, the distance increased to 21.1 +/- 3.0 mm. Clinically, a series of 7 cases of PL tibial plateau fractures were treated via this anterolateral supra-fibular-head approach. The patient was placed in a lateral decubitus position with the knee flexed to approximately 60 degrees. After the posterior retraction of the FCL, the plate was placed more posteriorly to provide a raft or horizontal belt fixation of the PL tibial plateau fragment. After an average of 14.3 months of follow up, the knee range of motion(ROM) was 121.4 degrees +/- 8.8 degrees (range: 105 degrees -135 degrees ), the HSS score was 96.7 +/- 2.6 (range: 90 100), and the SMFA dysfunction score was 22.4 +/- 3.8 (range: 16-28) points. CONCLUSION: The anterolateral supra-fibular-head approach can provide direct visualization of the posterolateral tibial plateau quadrant and put the plate more posteriorly to provide a raft for the fragments such that good clinical outcomes can be anticipated. PMID- 26684173 TI - The differential associations of preexisting conditions with trauma-related outcomes in the presence of competing risks. AB - INTRODUCTION: Pre-existing chronic conditions (PECs) pose a unique problem for the care of aging trauma populations. However, the relationships between specific conditions and outcomes after injury are relatively unknown. Evaluation of trauma patients is further complicated by their discharge to care facilities, where mortality risk remains high. Traditional approaches for evaluating in-hospital mortality do not account for the discharge of at-risk patients, which constitutes a competing risk event to death. The objective of this study was to evaluate associations between 40 PECs and two clinical outcomes in the context of competing risks among older trauma patients. METHODS: This retrospective study evaluated blunt-injured patients aged 55 years and older admitted to a level I trauma centre in 2006-2012. Outcomes were hospital length of stay (HLOS) and in hospital mortality. Survivors were classified as discharges home or discharges to care facilities. Competing risks regression was used to evaluate each PEC with in hospital mortality, accounting for discharges to care facilities as competing events. Competing risk estimates were compared to Cox model estimates, for which all survivors to discharge were non-events. Analyses were stratified using injury based mortality risk at a 50% cutpoint (high versus low). RESULTS: Among 4653 patients, 176 died in-hospital, 3059 were discharged home, and 1418 were discharged to a care facility. Most patients (98%) were classified with a low mortality risk. Only haemophilia and coagulopathy were consistently associated with longer HLOS. In the low-risk subgroup, in-hospital mortality was most strongly associated with liver diseases, haemophilia, and coagulopathy. In the high-risk group, Parkinson's disease, depression, and cancers showed the strongest associations. Accounting for the competing event altered estimates for 12 of 19 significant conditions. CONCLUSIONS: Excess mortality among patients expected to survive their injuries may be attributable to complications resulting from PECs. Discharges to care facilities constitute a bias in the evaluation of in-hospital mortality and should be considered for the accurate calculation of risk. In conjunction with injury measures, consideration of PECs provides physicians with a foundation to plan clinical decisions in older trauma patients. PMID- 26684174 TI - Production and characterization of poly(3-hydroxy butyrate-co-3 hydroxyvalerate) (PHBV) by a novel halotolerant mangrove isolate. AB - A halophilic mangrove isolate identified by 16S rRNA sequence as a Bacillus spp. was found to be capable of using a broad range of carbon sources including monosaccharides (glucose and fructose), disaccharides (sucrose), pentoses (xylose and arabinose), various organic acids (acetic acid, propionic acid and octanoic acid) and even the acid pre-treated liquor (APL) of sugarcane trash, a lignocellulosic biomass, for growth and the production of polyhydroxyalkanoates (PHAs) such as poly(3-hydroxybutyrate, P3HB), poly(3-hydroxybutyrate-co-3 hydroxyvalerate, PHBV), and 4-hydroxyhexanoate, 4HHX). The study describes the innate ability of a wild-type culture for PHBV production by both propionate dependent and propionate independent pathways. The biopolymer was extracted and characterized physico-chemically. The PHBV yield from glucose was estimated to be 73% of biomass weight with a high 3-hydroxyvalerate fraction of 48mol%. Thereafter, spherical homogenous PHBV nanoparticles of ~164nm size were prepared for future applications. PMID- 26684175 TI - Integration of decentralized torrefaction with centralized catalytic pyrolysis to produce green aromatics from coffee grounds. AB - The aim of this work was to integrate decentralized torrefaction with centralized catalytic pyrolysis to convert coffee grounds into the green aromatic precursors of terephthalic acid, namely benzene, toluene, ethylbenzene, and xylenes (BTEX). An economic analysis of this bioproduct system was conducted to examine BTEX yields, biomass costs and their sensitivities. Model predictions were verified experimentally using pyrolysis GC/MS to quantify BTEX yields for raw and torrefied biomass. The production cost was minimized when the torrefier temperature and residence time were 239 degrees C and 34min, respectively. This optimization study found conditions that justify torrefaction as a pretreatment for making BTEX, provided that starting feedstock costs are below $58 per tonne. PMID- 26684176 TI - Improving composting as a post-treatment of anaerobic digestate. AB - This work investigated the influences of practical parameters upon composting of digestate. The yardsticks for evaluation were digestate stabilization, nitrogenous emissions mitigation and self-heating potential. The results suggest choosing an "active" bulking agent like dry wood chips (WC) which served as free water and nitrogen sink through composting. At an optimal volumetric WC:digestate mixing ratio of 4:1, nearly 90% of the initial NH4(+)/NH3 were fixed, which reduced significantly nitrogenous emissions. This mixing ratio also improved the stabilization and self-heating potential. Using small particle size WC increased narrowly O2 consumption and reduced NH3 emission. Storing used WC prior to recycling reduced 40% N2O emission compared to directly recycled WC. Recycling compost helped to decrease NH3 emission, but quadrupled N2O emission. The optimal aeration rate (15Lh(-1)kg OM0) which was lower compared to composting of organic waste, was enough to ensure the O2 supply and ameliorate the self-heating potential through composting of digestate. PMID- 26684178 TI - Synthesis and Reactivity of Group 4 Metal Benzyl Complexes Supported by Carbazolide-Based PNP Pincer Ligands. AB - This study focuses on the viability of the carbazole-based Cbzdiphos PNP pincer ligand as a stabilizing element for group 4 metal complexes, and both the diphenylphosphino- and di-isopropylphosphino-substituted Cbzdiphos protioligands 1(Ph)H and 1(iPr)H were used. Treatment of the lithiated protioligands with the corresponding chlorido precursor compounds of the metals (titanium, zirconium, and hafnium) afforded the trichlorido complexes [(Cbzdiphos(iPr))MCl3] 2(iPr)M and [(Cbzdiphos(Ph))MCl3] 2(Ph)M (M = Ti, Zr, Hf), which were converted to the corresponding iodido complexes [(Cbzdiphos(iPr))MI3] 3(iPr)M and [(Cbzdiphos(Ph))MI3] 3(Ph)M (M = Ti, Zr, Hf) by reaction with an excess of trimethylsilyl iodide. Reaction of 2(iPr)Ti and 3(Ph)Ti with 1 equiv of dibenzyl magnesium tetrahydrofuran adduct led to the formation of the alkylidene complexes 4(iPr)Ti and 5(Ph)Ti, respectively, while the zirconium and hafnium complexes 2(iPr)Zr and 3(Ph)Zr/Hf formed the cyclometalated monoalkyl compounds [(Cbzdiphos(iPr)-CH)ZrBnCl] 6(iPr)Zr as well as [(Cbzdiphos(Ph)-CH)MBnX] 6(Ph)Hf (X = Cl) and 7(Ph)Zr/Hf (X = I) under analogous reaction conditions. On the other hand, stirring 2(Ph)Zr with 0.25 equiv of tetrabenzyl zirconium afforded [(Cbzdiphos(Ph))ZrBnCl2] (8(Ph)Zr), which contained the PNP ligand intact, while its alkylation with benzyl potassium led to the formation of the cyclometalated monobenzyl complex [(Cbzdiphos(Ph)-CH)ZrBnCl] (6(Ph)Zr). The remaining coordination site occupied by the halogenido ligand in the cyclometalated monobenzyl complexes [(Cbzdiphos-CH)MBnX] 6(iPr)Zr, 6(Ph)Zr/Hf, and 7(Ph)Zr/Hf was readily benzylated by treatment with benzyl potassium to afford the cyclometalated dibenzyl complexes [(Cbzdiphos-CH)MBn2] 9(iPr)Zr and 9(Ph)Zr/Hf. Further reaction of 9(Ph)Zr with an excess of benzyl potassium led to the formation of the anionic tribenzyl zirconium ate complex [(Cbzdiphos-CH)MBn3]K (10(Ph)Zr). Upon heating a solution of 8(Ph)Zr in the presence of 1 mol equiv of trimethyl phosphine, one of the ligand methylene groups was deprotonated, yielding the cyclometalated complex [(Cbzdiphos(Ph)-CH)ZrCl2(PMe3)] 11(Ph)Zr. Finally, reaction of 7(Ph)Zr with methylene triphenylphosphorane produced the ortho-metalated product [(Cbzdiphos(Ph)-CH)Zr(o-C6H4PPh2CH2)I] (12(Ph)Zr), which is characterized by a slightly puckered five-membered Zr-C(48)-P(3)-C(49)-C(50) metallacycle. PMID- 26684177 TI - Cylindrofridins A-C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale. AB - A rapid and exhaustive one-step biomass extraction as well as an enrichment and cleanup procedure has been developed for HPLC-UV detection and quantification of closely related [7.7]paracyclophanes and structural derivatives based on a two phase solvent system. The procedure has been validated using the biomass of the carbamidocyclophane- and cylindrocyclophane-producing cyanobacterium Nostoc sp. CAVN2 and was utilized to perform a screening comprising 102 cyanobacterial strains. As a result, three new cylindrocyclophane-related alkylresorcinols, cylindrofridins A-C (1-3), and known cylindrocyclophanes (4-6) were detected and isolated from Cylindrospermum stagnale PCC 7417. Structures of 1-3 were elucidated by a combination of 1D and 2D NMR experiments, HRMS, and ECD spectroscopy. Cylindrofridin A (1) is the first naturally occurring [7.7]paracyclophane-related monomeric derivative. In contrast, cylindrofridins B (2) and C (3) represent dimers related to 1. Due to chlorination at the alkyl carbon atom in 1-3, the site of [7.7]paracyclophane macrocycle formation, the cylindrofridins represent linearized congeners of the cylindrocyclophanes. Compounds 1-3 were not toxic against nontumorigenic HaCaT cells (IC50 values >25 MUM) compared to the respective cylindrocyclophanes, but 1 was the only cylindrofridin showing moderate activity against methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae with MIC values of 9 and 17 MUM, respectively. PMID- 26684179 TI - Tubulocystic renal cell carcinoma disguised as a renal cyst. AB - Even though CT scans are considered the gold standard to characterize a renal mass, sometimes they can be misleading, showing a solid renal mass as a cystic one. Tubulocystic renal cell carcinoma (TcRCC) is a rare and recently discovered RCC variant which radiologically may look like a Bosniak type II to IV, even if it has solid features. We describe a case of a patient with left kidney TcRCC initially diagnosed as a renal cyst, who finally underwent radical nephrectomy showing a large, solid neoplasm. Due to its unusual CT appearance, TcRCC can be confused with cystic lesions and several other benign or malignant entities. Ultrasound can be a useful aid for the characterization of these renal tumors. PMID- 26684180 TI - Lymph node imaging in bladder cancer. AB - Staging of muscle invasive bladder cancer (MIBC) remains a challenge. It is generally acknowledged that the most commonly used imaging techniques have a trend either to upstage or downstage the disease. The aim of this review article is to evaluate the currently available scientific evidence for the use of imaging modalities in preoperative bladder cancer staging with special attention to detection of lymph node metastasis (LNM). A non-systematic literature search utilizing PUBMED database with terms MIBC and LN and MRI or PET or CT was performed with the search limited to articles published between 2010-2015. Magnetic resonance imaging (MRI) has shown potential for local tumor detection and staging in multiple studies, but the accuracy for LNM detection remains disappointingly low. The LN staging accuracy is improved with the use of ultra small super-paramagnetic particles of iron oxide (USPIO). This experimental method, however, is not commercially available at the moment. Positron emission tomography (PET), a functional imaging technique most commonly accompanied with computed tomography (PET/CT), may also have a role in the detection of bladder cancer LNM in the future. According to the currently available scientific evidence, the following could be recommended for MIBC staging: 1. use of pelvic MRI for primary tumor evaluation and local LNM detection acknowledging limited nodal imaging accuracy; 2. pelvic/abdominal/chest CT for evaluation of distant metastasis. The scientific evidence does not support the routine use of PET/CT (18F-FDG, 18F/11C-choline, 11C-acetate) in bladder cancer staging or in LNM detection. PMID- 26684181 TI - Utility of lymphadenectomy following cystectomy for non-urothelial bladder cancer: a systematic review. AB - INTRODUCTION: Non-urothelial bladder cancer patients represent a rare and challenging group. Advances in bladder cancer to date have largely been driven by studies investigating common urothelial bladder tumors. New evidence is emerging supporting lymphadenectomy in standard surgical management of muscle invasive bladder cancer. We aim to explore the utility of lymphadenectomy in non urothelial bladder cancer. EVIDENCE ACQUISITION: A systematic review of the available peer-reviewed literature on PubMed was performed using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search strategy. Tumors included in our analysis were squamous cell carcinomas, adenocarcinomas, paragangliomas, melanomas and sarcomas. EVIDENCE SYNTHESIS: Our search strategy identified 8168 unique records and we included 135 full text articles in our final qualitative analysis. No comparative studies comparing lymphadenectomy outcomes in non-urothelial bladder tumors were identified. Practice of lymphadenectomy in combination with partial or radical cystectomy in the treatment of non-urothelial bladder cancer is relatively common. Pelvic recurrence following radical or partial cystectomy of non-urothelial tumors was more commonly reported in non-lymphadenectomy cohorts. The exception to this observation was the adenocarcinoma cohort. CONCLUSIONS: Current evidence supporting lymphadenectomy in the surgical management of bladder cancer is largely based on studies limited to urothelial cancer. Despite this, the practice of lymphadenectomy in non-urothelial cancer is common. We support lymphadenectomy in non-urothelial bladder cancer given the minimal risk associated with the procedure and the potential for improved survival. PMID- 26684182 TI - Exploring Memory Representations with Activity-Based Genetics. AB - The brain is thought to represent specific memories through the activity of sparse and distributed neural ensembles. In this review, we examine the use of immediate early genes (IEGs), genes that are induced by neural activity, to specifically identify and genetically modify neurons activated naturally by environmental experience. Recent studies using this approach have identified cellular and molecular changes specific to neurons activated during learning relative to their inactive neighbors. By using opto- and chemogenetic regulators of neural activity, the neurons naturally recruited during learning can be artificially reactivated to directly test their role in coding external information. In contextual fear conditioning, artificial reactivation of learning induced neural ensembles in the hippocampus or neocortex can substitute for the context itself. That is, artificial stimulation of these neurons can apparently cause the animals to "think" they are in the context. This represents a powerful approach to testing the principles by which the brain codes for the external world and how these circuits are modified with learning. PMID- 26684183 TI - Adult Neurogenesis: An Evolutionary Perspective. AB - When adult neurogenesis was discovered in the mammalian brain it was often considered an atavism and, even today, many people are convinced that there has been a "phylogenetic reduction" away from lifelong neurogenesis, favoring stability for complex brains. Adult neurogenesis is found throughout the animal kingdom but varies to a large extent. Mammals might have fewer neurogenic zones than, for example, fish, but within their remaining neurogenic zones, the new neurons are highly functional. Especially, humans have very substantial quantities of neurogenesis in their hippocampus. At least for the mammalian dentate gyrus, one can thus argue that there has been evolution toward neurogenesis-based plasticity rather than away from it. PMID- 26684185 TI - [Rehabilitation after kidney transplantation: Old problems and new structures]. AB - Kidney transplantation is currently the best therapeutic option for patients with end stage renal disease. Alternative treatment with hemo- or peritoneal dialysis is associated with higher comorbidities, higher morbidity/mortality, and reduced quality of life. Thus, a major aim in posttransplant care is to develop strategies to increase transplant survival and reduce known risk factors and comorbidities. In this overview, we propose a concept to include rehabilitation clinics in all aspects of the transplant process. This concept includes pretransplant care on the waiting list to prepare the patient for the transplant, the direct postoperative treatment phase, and repeated and risk adapted stays in rehabilitation clinics during long-term follow-up to address specific and individual problems. PMID- 26684186 TI - [Kikuchi-Fujimoto lymphadenitis in a 29-year-old female patient]. AB - We report the case of a 29-year-old Turkish woman who was admitted to hospital with a 4-week history of fever up to 39.0 degrees C, headache, sore throat, fatigue and painful cervical and right-sided axillary lymph node swelling. Computed tomography imaging of the neck, thorax and abdomen identified generalized but in particular bilateral cervical and right-sided axillary lymph node enlargement (up to 2 cm). The histological examination of the axillary lymph node biopsy revealed Kikuchi-Fujimoto disease (KFD), a condition characterized by histiocytic necrotizing lymphadenitis. The patient was treated symptomatically with analgesics and antipyretics and the symptoms and febrile condition slowly improved. PMID- 26684184 TI - Early Microbial Evolution: The Age of Anaerobes. AB - In this article, the term "early microbial evolution" refers to the phase of biological history from the emergence of life to the diversification of the first microbial lineages. In the modern era (since we knew about archaea), three debates have emerged on the subject that deserve discussion: (1) thermophilic origins versus mesophilic origins, (2) autotrophic origins versus heterotrophic origins, and (3) how do eukaryotes figure into early evolution. Here, we revisit those debates from the standpoint of newer data. We also consider the perhaps more pressing issue that molecular phylogenies need to recover anaerobic lineages at the base of prokaryotic trees, because O2 is a product of biological evolution; hence, the first microbes had to be anaerobes. If molecular phylogenies do not recover anaerobes basal, something is wrong. Among the anaerobes, hydrogen-dependent autotrophs--acetogens and methanogens--look like good candidates for the ancestral state of physiology in the bacteria and archaea, respectively. New trees tend to indicate that eukaryote cytosolic ribosomes branch within their archaeal homologs, not as sisters to them and, furthermore tend to root archaea within the methanogens. These are major changes in the tree of life, and open up new avenues of thought. Geochemical methane synthesis occurs as a spontaneous, abiotic exergonic reaction at hydrothermal vents. The overall similarity between that reaction and biological methanogenesis fits well with the concept of a methanogenic root for archaea and an autotrophic origin of microbial physiology. PMID- 26684187 TI - Involvement of aberrant calcium signalling in herpetic neuralgia. AB - Alpha-herpesviruses, herpes simplex viruses (HSV) and varicella zoster virus (VZV), are pathogens of the peripheral nervous system. After primary infection, these viruses establish latency within sensory ganglia, while retaining the ability to reactivate. Reactivation of VZV results in herpes zoster, a condition characterized by skin lesions that leads to post-herpetic neuralgia. Recurrent reactivations of HSV, which cause mucocutaneous lesions, may also result in neuralgia. During reactivation of alpha-herpesviruses, satellite glial cells (SGCs), which surround neurons in sensory ganglia, become infected with the replicating virus. SGCs are known to contribute to neuropathic pain in a variety of animal pain models. Here we investigated how infection of short-term cultures of mouse trigeminal ganglia with HSV-1 affects communication between SGCs and neurons, and how this altered communication may increase neuronal excitability, thus contributing to herpetic neuralgia. Mechanical stimulation of single neurons or SGCs resulted in intercellular calcium waves, which were larger in cultures infected with HSV-1. Two differences were observed between control and HSV-1 infected cultures that could account for this augmentation. Firstly, HSV-1 infection induced cell fusion among SGCs and neurons, which would facilitate the spread of calcium signals over farther distances. Secondly, using calcium imaging and intracellular electrical recordings, we found that neurons in the HSV-1 infected cultures exhibited augmented influx of calcium upon depolarization. These virally induced changes may not only cause more neurons in the sensory ganglia to fire action potentials, but may also increase neurotransmitter release at the presynaptic terminals in the spinal cord. They are therefore likely to be contributing factors to herpetic neuralgia. PMID- 26684189 TI - 'This Is Real Misery': Experiences of Women Denied Legal Abortion in Tunisia. AB - Barriers to accessing legal abortion services in Tunisia are increasing, despite a liberal abortion law, and women are often denied wanted legal abortion services. In this paper, we seek to explore the reasons for abortion denial and whether these reasons had a legal or medical basis. We also identify barriers women faced in accessing abortion and make recommendations for improved access to quality abortion care. We recruited women immediately after they had been turned away from legal abortion services at two facilities in Tunis, Tunisia. Thirteen women consented to participate in qualitative interviews two months after they were turned away from the facility. Women were denied abortion care on the day they were recruited due to three main reasons: gestational age, health conditions, and logistical barriers. Nine women ultimately terminated their pregnancies at another facility, and four women carried to term. None of the women attempted illegal abortion services or self-induction. Further research is needed in order to assess abortion denial from the perspective of providers and medical staff. PMID- 26684188 TI - Multimorbidity and Its Patterns according to Immigrant Origin. A Nationwide Register-Based Study in Norway. AB - INTRODUCTION: As the flows of immigrant populations increase worldwide, their heterogeneity becomes apparent with respect to the differences in the prevalence of chronic physical and mental disease. Multimorbidity provides a new framework in understanding chronic diseases holistically as the consequence of environmental, social, and personal risks that contribute to increased vulnerability to a wide variety of illnesses. There is a lack of studies on multimorbidity among immigrants compared to native-born populations. METHODOLOGY: This nationwide multi-register study in Norway enabled us i) to study the associations between multimorbidity and immigrant origin, accounting for other known risk factors for multimorbidity such as gender, age and socioeconomic levels using logistic regression analyses, and ii) to identify patterns of multimorbidity in Norway for immigrants and Norwegian-born by means of exploratory factor analysis technique. RESULTS: Multimorbidity rates were lower for immigrants compared to Norwegian-born individuals, with unadjusted odds ratios (OR) and 95% confidence intervals 0.38 (0.37-0.39) for Eastern Europe, 0.58 (0.57-0.59) for Asia, Africa and Latin America, and 0.67 (0.66-0.68) for Western Europe and North America. Results remained significant after adjusting for socioeconomic factors. Similar multimorbidity disease patterns were observed among Norwegian-born and immigrants, in particular between Norwegian-born and those from Western European and North American countries. However, the complexity of patterns that emerged for the other immigrant groups was greater. Despite differences observed in the development of patterns with age, such as ischemic heart disease among immigrant women, we were unable to detect the systematic development of the multimorbidity patterns among immigrants at younger ages. CONCLUSIONS: Our study confirms that migrants have lower multimorbidity levels compared to Norwegian-born. The greater complexity of multimorbidity patterns for some immigrant groups requires further investigation. Health care policies and practice will require a holistic approach for specific population groups in order to meet their health needs and to curb and prevent diseases. PMID- 26684190 TI - Sexology in Portugal: Narratives by Portuguese Sexologists. AB - This article presents the emergence and development of modern sexology in Portugal through the analysis of Portuguese sexologists' narratives, to explore how they commit to a professional identity as sexologists, and to discuss how they integrate their professional role into the vast multidisciplinary field of sexology. In-depth interviews were conducted with 44 key professionals, purposefully recruited to guarantee heterogeneity concerning generation, gender, training, and practice. Content analysis focused on highlighting differences and articulations among the main professionals making up the field. The findings indicate that sexology is not seen as a full-fledged profession but rather as a specialization or a secondary field of action. The sexual medicine perspective is prevalent and more visible among physicians, thus reflecting the gap between psychosocial and biomedical approaches. A close link between clinical work and research and a gap between clinical work and health promotion were found. Despite the multidisciplinary nature of sexology being acknowledged, it is not fully implemented by the experts in the field. However, it is this characteristic that permitted sexology to institutionalize and to legitimate itself as a discourse of truth about sex, in Portugal as in other countries. PMID- 26684191 TI - Mutation analysis of MUTYH in Japanese colorectal adenomatous polyposis patients. AB - Germline MUTYH mutations were investigated in 14 Japanese colorectal polyposis patients without germ line adenomatous polyposis coli (APC) gene mutations. Three patients had a heterozygous IVS10-2A>G MUTYH mutation. The onset of MUTYH associated polyposis (MAP) occurs later than that of familial adenomatous polyposis with germline APC mutation. Thus, we compared the carrier frequency of MUTYH IVS10-2A>G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment. The frequency of IVS10-2A>G heterozygote in APC germline mutation negative polyposis patients was significantly higher than control subject (p = 0.012, Chi square test). Although the sample size is still too small to conclude, the IVS10 2A>G MUTYH heterozygote might add to the risk of developing germline APC mutation negative polyposis. PMID- 26684192 TI - Methods for the cultivation of ciliated protozoa from the large intestine of horses. AB - This paper describes cultivation methods for ciliates from the digestive tract of horses. Members of three different genera were successfully grown in vitro for short periods of time. However, only cells belonging to the genus Blepharocorys, which resides in the horse's large intestine, were maintained for longer periods. This Blepharocorys culture was successfully grown in vitro after inoculation of freshly excreted horse faeces in culture medium containing a population of bacteria. The ciliates survived for over six months, and the density of their population varied between 1.7 * 10(3) and 2.4 * 10(3) cells mL(-1). Favourable conditions for the prolonged cultivation of this ciliate were observed when the medium was prepared by mixing horse faeces and 'caudatum' salt solution in a 1:1 V/V ratio together with food (60% powdered meadow hay, 16% wheat gluten, 12% barley flour and 12% microcrystalline cellulose) supplied as 0.20 mg mL(-1) culture per day. PMID- 26684193 TI - Single Molecule Hydrodynamic Separation Allows Sensitive and Quantitative Analysis of DNA Conformation and Binding Interactions in Free Solution. AB - Limited tools exist that are capable of monitoring nucleic acid conformations, fluctuations, and distributions in free solution environments. Single molecule free solution hydrodynamic separation enables the unique ability to quantitatively analyze nucleic acid biophysics in free solution. Single molecule fluorescent burst data and separation chromatograms can give layered insight into global DNA conformation, binding interactions, and molecular distributions. First, we show that global conformation of individual DNA molecules can be directly visualized by examining single molecule fluorescent burst shapes and that DNA exists in a dynamic equilibrium of fluctuating conformations as it is driven by Poiseuille flow through micron-sized channels. We then show that this dynamic equilibrium of DNA conformations is reflected as shifts in hydrodynamic mobility that can be perturbed using salt and ionic strength to affect packing density. Next, we demonstrate that these shifts in hydrodynamic mobility can be used to investigate hybridization thermodynamics and binding interactions. We distinguish and classify multiple interactions within a single sample, and demonstrate quantification amidst large concentration differences for the detection of rare species. Finally, we demonstrate that these differences can resolve perfect complement, 2 bp mismatched, and 3 bp mismatched sequences. Such a system can be used to garner diverse information about DNA conformation and structure, and potentially be extended to other molecules and mixed-species interactions, such as between nucleic acids and proteins or synthetic polymers. PMID- 26684194 TI - PhysarumSpreader: A New Bio-Inspired Methodology for Identifying Influential Spreaders in Complex Networks. AB - Identifying influential spreaders in networks, which contributes to optimizing the use of available resources and efficient spreading of information, is of great theoretical significance and practical value. A random-walk-based algorithm LeaderRank has been shown as an effective and efficient method in recognizing leaders in social network, which even outperforms the well-known PageRank method. As LeaderRank is initially developed for binary directed networks, further extensions should be studied in weighted networks. In this paper, a generalized algorithm PhysarumSpreader is proposed by combining LeaderRank with a positive feedback mechanism inspired from an amoeboid organism called Physarum Polycephalum. By taking edge weights into consideration and adding the positive feedback mechanism, PhysarumSpreader is applicable in both directed and undirected networks with weights. By taking two real networks for examples, the effectiveness of the proposed method is demonstrated by comparing with other standard centrality measures. PMID- 26684195 TI - Correction: Overexpression of Mineralocorticoid Receptors Partially Prevents Chronic Stress-Induced Reductions in Hippocampal Memory and Structural Plasticity. PMID- 26684196 TI - A study to quantify the effect of patient motion and develop methods to detect and correct for motion during myocardial perfusion imaging on a CZT solid-state dedicated cardiac camera. AB - BACKGROUND: Due to differences in the design and acquisition parameters on the solid-state CZT cardiac camera the effect of patient motion may vary compared to Anger cameras. This study evaluates the effect of motion, two new methods of three-dimensional (3D) motion detection and a method of motion correction. METHOD: Phantom acquisitions were offset in the X, Y, and Z directions and combined to simulate different types of motion. Motion artifacts were identified using the total perfusion defect and blinded visual interpretation. Motion was detected by registering planar and reconstructed 30 second images, and corrected by summing the aligned reconstructed images. Validation was performed on phantom data. These techniques were then applied to 40 patient studies. RESULTS: Motion >=10 mm and >=60 seconds in duration introduced significant artifacts. There was no significant difference (P = .258) between the two methods of motion detection. Motion correction removed artifacts from 9/10 phantom simulations. Superior inferior motion >=8 mm was measured on 10% of patient studies, and 5% were affected by motion. Motion in the lateral and anterior-posterior directions was <8 mm. CONCLUSION: Superior-inferior patient motion artifacts have been identified on myocardial perfusion images acquired on a CZT camera. Routine QC to identify studies with significant motion is recommended. PMID- 26684197 TI - Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy. AB - BACKGROUND: Triple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease. PURPOSE: The aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC. METHODS: We analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients. RESULTS: We identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42-6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28-5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71-18.31]). CONCLUSION: This study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as two other promising prognostic factors in this breast cancer subgroup. Using these clinical factors, we were able to classify TNBC patients in 5 subgroups, for which pre-menopausal patients with grade III tumors and lymph node involvement after NAC have the worse prognosis. PMID- 26684198 TI - EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients. AB - BACKGROUND: Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations. METHOD/DESIGN: The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement. DISCUSSION: With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors. TRIAL REGISTRATION: NCT02544178. PMID- 26684200 TI - Early adoption of screening and the changing pattern of cervical cancer in UK military women: evidence from the Scottish Veterans Health Study. AB - OBJECTIVE: To examine the risk of cervical cancer in a large national cohort of military veteran women followed up for up to 30 years. METHODS: Retrospective cohort study of 5235 veteran women born between 1945 and 1985, and 20 703 women with no record of service matched for age and area of residence, using Cox proportional hazard models to compare the overall risk of cervical cancer and by year of birth. RESULTS: During the follow-up period 1981-2012, there were 18 (0.34%) cases of cervical cancer in the veteran women compared with 81 (0.39%) in the non-veterans. The difference was not statistically significant overall (adjusted HR 0.95, 95% CI 0.57 to 1.59). When analysed by the year of birth, veteran women born in 1958 and earlier had a non-significantly higher risk than non-veterans (adjusted HR 1.24, 95% CI 0.68 to 2.26), while veteran women born after 1958 had a non-significant reduction in risk (adjusted HR 0.51, 95% CI 0.18 to 1.44). CONCLUSIONS: Women born after 1958 who have served in the Armed Forces are at reduced risk of cervical cancer compared with women who have never served, and compared with older veteran women. Small numbers of cases precluded statistical significance. The change in risk pattern in veteran women coincided with the introduction of cervical screening in the Armed Forces, which predated the UK national programme, and provides evidence for the long-term effectiveness of the Armed Forces' sexual health strategy. The impact of recent changes in the screening age, and of human papillomavirus immunisation, should be monitored in the future. PMID- 26684199 TI - Multi-trophic interactions driving the transmission cycle of Borrelia afzelii between Ixodes ricinus and rodents: a review. AB - The tick Ixodes ricinus is the main vector of the spirochaete Borrelia burgdorferi sensu lato, the causal agent of Lyme borreliosis, in the western Palearctic. Rodents are the reservoir host of B. afzelii, which can be transmitted to I. ricinus larvae during a blood meal. The infected engorged larvae moult into infected nymphs, which can transmit the spirochaetes to rodents and humans. Interestingly, even though only about 1% of the larvae develop into a borreliae-infected nymph, the enzootic borreliae lifecycle can persist. The development from larva to infected nymph is a key aspect in this lifecycle, influencing the density of infected nymphs and thereby Lyme borreliosis risk. The density of infected nymphs varies temporally and geographically and is influenced by multi-trophic (tick-host-borreliae) interactions. For example, blood feeding success of ticks and spirochaete transmission success differ between rodent species and host-finding success appears to be affected by a B. afzelii infection in both the rodent and the tick. In this paper, we review the major interactions between I. ricinus, rodents and B. afzelii that influence this development, with the aim to elucidate the critical factors that determine the epidemiological risk of Lyme borreliosis. The effects of the tick, rodent and B. afzelii on larval host finding, larval blood feeding, spirochaete transmission from rodent to larva and development from larva to nymph are discussed. Nymphal host finding, nymphal blood feeding and spirochaete transmission from nymph to rodent are the final steps to complete the enzootic B. afzelii lifecycle and are included in the review. It is concluded that rodent density, rodent infection prevalence, and tick burden are the major factors affecting the development from larva to infected nymph and that these interact with each other. We suggest that the B. afzelii lifecycle is dependent on the aggregation of ticks among rodents, which is manipulated by the pathogen itself. Better understanding of the processes involved in the development and aggregation of ticks results in more precise estimates of the density of infected nymphs, and hence predictions of Lyme borreliosis risk. PMID- 26684202 TI - Efficient Gene Induction and Endogenous Gene Repression Systems for the Filamentous Cyanobacterium Anabaena sp. PCC 7120. AB - In the last decade, many studies have been conducted to employ genetically engineered cyanobacteria in the production of various metabolites. However, the lack of a strict gene regulation system in cyanobacteria has hampered these attempts. The filamentous cyanobacterium Anabaena sp. PCC 7120 performs both nitrogen and carbon fixation and is, therefore, a good candidate organism for such production. To employ Anabaena cells for this purpose, we intended to develop artificial gene regulation systems to alter the cell metabolic pathways efficiently. We introduced into Anabaena a transcriptional repressor TetR, widely used in diverse organisms, and green fluorescent protein (GFP) as a reporter. We found that anhydrotetracycline (aTc) substantially induced GFP fluorescence in a concentration-dependent manner. By expressing tetR under the nitrate-specific promoter nirA, we successfully reduced the concentration of aTc required for the induction of gfp under nitrogen fixation conditions (to 10% of the concentration needed under nitrate-replete conditions). Further, we succeeded in the overexpression of GFP by depletion of nitrate without the inducer by means of promoter engineering of the nirA promoter. Moreover, we applied these gene regulation systems to a metabolic enzyme in Anabaena and successfully repressed glnA, the gene encoding glutamine synthetase that is essential for nitrogen assimilation in cyanobacteria, by expressing the small antisense RNA for glnA. Consequently, the ammonium production of an ammonium-excreting Anabaena mutant was significantly enhanced. We therefore conclude that the gene regulation systems developed in this study are useful tools for the regulation of metabolic enzymes and will help to increase the production of desired substances in Anabaena. PMID- 26684203 TI - Honouring top reviewers, and what makes a great peer review? PMID- 26684201 TI - The Eukaryotic Mismatch Recognition Complexes Track with the Replisome during DNA Synthesis. AB - During replication, mismatch repair proteins recognize and repair mispaired bases that escape the proofreading activity of DNA polymerase. In this work, we tested the model that the eukaryotic mismatch recognition complex tracks with the advancing replisome. Using yeast, we examined the dynamics during replication of the leading strand polymerase Polepsilon using Pol2 and the eukaryotic mismatch recognition complex using Msh2, the invariant protein involved in mismatch recognition. Specifically, we synchronized cells and processed samples using chromatin immunoprecipitation combined with custom DNA tiling arrays (ChIP-chip). The Polepsilon signal was not detectable in G1, but was observed at active origins and replicating DNA throughout S-phase. The Polepsilon signal provided the resolution to track origin firing timing and efficiencies as well as replisome progression rates. By detecting Polepsilon and Msh2 dynamics within the same strain, we established that the mismatch recognition complex binds origins and spreads to adjacent regions with the replisome. In mismatch repair defective PCNA mutants, we observed that Msh2 binds to regions of replicating DNA, but the distribution and dynamics are altered, suggesting that PCNA is not the sole determinant for the mismatch recognition complex association with replicating regions, but may influence the dynamics of movement. Using biochemical and genomic methods, we provide evidence that both MutS complexes are in the vicinity of the replisome to efficiently repair the entire spectrum of mutations during replication. Our data supports the model that the proximity of MutSalpha/beta to the replisome for the efficient repair of the newly synthesized strand before chromatin reassembles. PMID- 26684205 TI - A prospective multicenter study on self-expandable metallic stents as a bridge to surgery for malignant colorectal obstruction in Japan: efficacy and safety in 312 patients. AB - BACKGROUND: Endoscopic stenting with a self-expandable metallic stent (SEMS) is a widely accepted procedure for malignant colonic obstruction. The Colonic Stent Safe Procedure Research Group conducted the present prospective feasibility study. METHODS: Our objectives were to estimate the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction. We conducted a prospective, observational, single-arm, multicenter clinical trial from March 2012 to October 2013. Each patient was treated with an uncovered WallFlex enteral colonic stent. Patients were followed up until discharge after surgery. RESULTS: A total of 518 consecutive patients were enrolled in this study. The cohort intended for BTS consisted of 312 patients (61 %), and the stent could be released in 305 patients. Technical and clinical success rates were 98 and 92 %, respectively. Elective surgery was performed in 297 patients, and emergency surgery was performed in eight patients for the treatment of complications. The overall preoperative complication rate was 7.2 %. Major complications, including perforation, occurred in 1.6 %, persistent colonic obstruction occurred in 1.0 %, and stent migration occurred in 1.3 % patients. The median time from SEMS to surgery was 16 days. Silent perforations were observed in 1.3 %. Open and laparoscopic surgery was performed in 121 and 184 patients, respectively. The tumor could be resected in 297 patients. The primary anastomosis rate was 92 %. The rate of anastomotic leakage was 4 %, and the overall stoma creation rate was 10 %. The median duration of hospitalization following surgery was 12 days. Overall postoperative morbidity and mortality rates were 16 and 0.7 %, respectively. CONCLUSIONS: This largest, multicenter, prospective study demonstrates the feasibility of SEMS placement as a BTS for malignant colorectal obstruction. SEMS serves as a safe and effective BTS with acceptable stoma creation and complication rates in patients with acute malignant colonic obstruction. PMID- 26684207 TI - SpyGlass cholangioscopy-assisted guidewire placement for post-LDLT biliary strictures: a case series. AB - BACKGROUND AND AIMS: Anastomotic biliary strictures are common in patients that undergo living donor liver transplantation. Although endoscopic management has the advantage over percutaneous approaches, the initial success rate for the endoscopic management is unsatisfactory. The SpyGlass system can be a useful device in patients with a severe anastomotic stricture. METHODS: The SpyGlass cholangioscopy-assisted guidewire placement was performed in 15 patients with a difficult guidewire placement in which the guidewire could not transverse the stricture with conventional methods for 10 min or more. RESULTS: The visualization rate of the stricture orifice was 93.3 % (14 of 15 patients). The total success rate of the SpyGlass cholangioscopy-assisted guidewire placement was 60 % (9 of 15 patients). No procedure-related complications occurred during or after the SpyGlass cholangioscopy-assisted guidewire placement. CONCLUSIONS: This series demonstrated that the SpyGlass cholangioscopy-assisted guidewire placement is a useful method when the guidewire passage of the strictures site is impossible by conventional methods. PMID- 26684208 TI - Health effects of climate change highlighted in Paris Agreement. PMID- 26684206 TI - Preoperative risk factors of hemodynamic instability during laparoscopic adrenalectomy for pheochromocytoma. AB - BACKGROUND: Adrenalectomy for pheochromocytoma is considered to be a challenging procedure because of the risk of hemodynamic instability (HI), which is poorly defined and unpredictable. The objective of this retrospective study from a prospectively maintained database was to determine the predictive factors for perioperative HI, which is defined as a morbidity-related variable, in patients undergoing unilateral laparoscopic adrenalectomy (LA) for pheochromocytoma. METHODS: A total of 149 patients with unilateral pheochromocytoma undergoing LA were included. First, HI was defined using independent hemodynamic variables associated with perioperative morbidity. Next, a multivariable logistic regression analysis was performed to determine the independent preoperative risk factors for HI. RESULTS: There was no postoperative mortality, and the overall morbidity rate was 10.7 %. The use of a cumulative dose of norepinephrine >5 mg was the only independent hemodynamic predictive factor for postoperative complications; thus, this variable was used to define HI. A multivariate analysis revealed that a symptomatic high preoperative blood pressure (p = 0.003) and a ten-fold increase in urinary metanephrine and/or normetanephrine levels (p < 0.0001) were significant predictors of HI. When no predictive factors were present, the risk of HI and the postoperative morbidity were 1.5 and 4.3 %, respectively. However, when two predictive factors were present, the HI risk and the postoperative morbidity were 53.8 and 30.8 %, respectively. CONCLUSION: Perioperative HI, defined as the need for a cumulative dose of norepinephrine >5 mg, is significantly associated with postoperative morbidity and can be predicted by symptomatic preoperative high blood pressure and above a ten-fold increase in urinary metanephrine and/or normetanephrine levels. PMID- 26684209 TI - Evolution and molecular epidemiology of classical swine fever virus during a multi-annual outbreak amongst European wild boar. AB - Classical swine fever is a viral disease of pigs that carries tremendous socio economic impact. In outbreak situations, genetic typing is carried out for the purpose of molecular epidemiology in both domestic pigs and wild boar. These analyses are usually based on harmonized partial sequences. However, for high resolution analyses towards the understanding of genetic variability and virus evolution, full-genome sequences are more appropriate. In this study, a unique set of representative virus strains was investigated that was collected during an outbreak in French free-ranging wild boar in the Vosges-du-Nord mountains between 2003 and 2007. Comparative sequence and evolutionary analyses of the nearly full length sequences showed only slow evolution of classical swine fever virus strains over the years and no impact of vaccination on mutation rates. However, substitution rates varied amongst protein genes; furthermore, a spatial and temporal pattern could be observed whereby two separate clusters were formed that coincided with physical barriers. PMID- 26684210 TI - Health professional perspectives on systems failures in transitional care for patients with dementia and their carers: a qualitative descriptive study. AB - BACKGROUND: Healthcare professionals engage in discharge planning of people with dementia during hospitalisation, however plans for transitioning the person into community services can be patchy and ineffective. The aim of this study was to report acute, community and residential care health professionals' (HP) perspectives on the discharge process and transitional care arrangements for people with dementia and their carers. METHODS: A qualitative descriptive study design and purposive sampling was used to recruit HPs from four groups: Nurses and allied health practitioners involved in discharge planning in the acute setting, junior medical officers in acute care, general practitioners (GPs) and Residential Aged Care Facility (RACF) staff in a regional area in NSW, Australia. Focus group discussions were conducted using a semi-structured schedule. Content analysis was used to understand the discharge process and transitional care arrangements for people with dementia (PWD) and their carers. RESULTS: There were 33 participants in four focus groups, who described discharge planning and transitional care as a complex process with multiple contributors and components. Two main themes with belonging sub-themes derived from the analysis were: Barriers to effective discharge planning for PWD and their carers - the acute care perspective: managing PWD in the acute care setting, demand for post discharge services exceeds availability of services, pressure to discharge patients and incomplete discharge documentation. Transitional care process failures and associated outcomes for PWD - the community HP perspective: failures in delivery of services to PWD; inadequate discharge notification and negative patient outcomes; discharge-related adverse events, readmission and carer stress; and issues with medication discharge orders and outcomes for PWD. CONCLUSIONS: Although acute care HPs do engage in required discharge planning for people with dementia, participants identified critical issues: pressure on acute care health professionals to discharge PWD early, the requirement for JMOs to complete discharge summaries, the demand for post discharge services for PWD exceeding supply, the need to modify post discharge medication prescriptions for PWD, the need for improved coordination with RACF, and the need for routine provision of medication dose decision aids and home medicine reviews post discharge for PWD and their carers. PMID- 26684211 TI - Molecular imaging for stem cell therapy in the brain. AB - Molecular imaging is one of the methods to follow-up stem cell therapy by visualization in the brain. In a recent article in Stem Cell Research & Therapy, Micci et al. offer a thorough discussion of the advantages and disadvantages of this method and their roles in the future. The authors are among the very first who have implemented recently introduced molecular imaging techniques in experimental research and clinical practice. PMID- 26684212 TI - Immunogenetics of three novel HLA-Class II alleles: DRB1*03:112, DQB1*03:02:16 and DQB1*03:139. AB - Three novel HLA-Class II alleles, DRB1*03:112, DQB1*03:02:16 and DQB1*03:139, are described with predicted bearing haplotypes of A*02:01, B*40:01, C*03:04, DRB1*03:112, DQB1*02:01; A*23:01, B*15:01, C*03:03, DRB1*04:01, DQB1*03:02:16 and A*01:01, B*44:02, C*05:01/03, DRB1*04:01, DQB1*03:139. Serological tests showed that the DRB1*03:112 and DQB1*03:139 specificities failed to react as expected with some well-documented monoclonal antibodies. Subsequent examination of published HLA-Class II epitopes and inspection of amino acid motifs suggested that epitopes exist that include the positions of their single substitutions (F31C between DRB1*03:01:01:01 and DRB1*03:112, and R48P between DQB1*03:01:01:01 and DQB1*03:139 specificities). This suggests that the reactivity of the monoclonal antibodies used was dependent on these epitopes and that their loss from these rare allele products resulted in their aberrant serology. The new alleles were found after the sequence-based typing of 32 530 random UK European routine blood donors suggesting that each has a maximum carriage frequency of 0.0031% in the blood donor population resident in Wales. PMID- 26684213 TI - Rapid thyroid nodule growth is not a marker for well-differentiated thyroid cancer. AB - BACKGROUND: Rapid growth of thyroid nodules is described as being associated with thyroid cancer. The objective of the study was to determine how the growth rate of thyroid nodules during follow-up is associated with the risk of thyroid cancer. METHODS: Retrospective analysis of patients undergoing thyroid surgery for nodular disease and a repetitive preoperative ultrasound work-up of at least 6 months was done. Nodule growth was considered relevant when a volume increase >49% was detected. Growth patterns were described as rapid for a volume increase present over 6 to 24 months. RESULTS: Of the 297 analysed patients, 226 (76%) displayed relevant nodule growth and 71 (24%) no relevant growth. A rapid growth pattern was seen in 73 patients (32%). Well-differentiated thyroid cancer was diagnosed in 33 patients (11%; 27 papillary, 6 follicular) with a relevant nodule growth in 2 and no relevant growth in 31 patients. No rapid growth pattern was observed in any case of well-differentiated thyroid cancer. A rapid growth pattern occurred only in benign nodules (70 patients) and in 1 patient each with a lymphoma, a metastasis of a renal cell cancer and a metastasis of a gastric adenocarcinoma. Therapy with levothyroxine and/or iodine was administered to 129 patients (43%) and was significantly inversely correlated with nodule growth (odds ratio 0.27; CI 95 % 0.14-0.53, p < 0.001). CONCLUSIONS: Thyroid nodule growth alone and especially a rapid growth pattern during follow-up for thyroid nodular disease is not a marker for well-differentiated thyroid cancer and should not be used as a stand-alone argument for thyroid surgery. PMID- 26684214 TI - Therapeutic Neuroendocrine Agonist and Antagonist Analogs of Hypothalamic Neuropeptides as Modulators of the Hypothalamic-Pituitary-Gonadal Axis. AB - Reproductive hormones play a role at all stages of life and affect most tissues of the body. Gonadotropin-releasing hormone (GnRH) synthesized in the hypothalamus stimulates the secretion of gonadotropins which in turn stimulate gonadal sex hormone production and gamete formation. This hypothalamic-pituitary gonadal (HPG) axis has, therefore, been the target for the development of numerous drugs which regulate it at various points. These include sex steroid agonists and antagonists, inhibitors of sex steroid biosynthesis, and GnRH agonists and antagonists, which have found extensive applications in treating numerous conditions such as precocious puberty, delayed puberty, prostate cancer, benign prostatic hyperplasia, endometriosis, uterine fibroids and also in in vitro fertilization protocols. The novel neuroendocrine peptides, kisspeptin (KP) and neurokinin B (NKB), were recently discovered as upstream regulators of GnRH, and inactivating mutations of KP and NKB ligands or receptors result in a failure to progress through puberty. Agonists and antagonists of KP and NKB are being developed as more subtle modulators of the HPG axis. These new drugs offer additional and alternative therapeutic options in pediatric and adult hormone dependent diseases. PMID- 26684215 TI - Fabrication of free-standing lithium niobate nanowaveguides down to 50 nm in width. AB - Nonlinear optical nanoscale waveguides are a compact and powerful platform for efficient wavelength conversion. The free-standing waveguide geometry opens a range of applications in microscopy for local delivery of light, where in situ wavelength conversion helps to overcome various wavelength-dependent issues, such as biological tissue damage. In this paper, we present an original patterning method for high-precision fabrication of free-standing nanoscale waveguides based on lithium niobate, a material with a strong second-order nonlinearity and a broad transparency window covering the visible and mid-infrared wavelength ranges. The fabrication process combines electron-beam lithography with ion-beam enhanced etching and produces nanowaveguides with lengths from 5 to 50 MUm, widths from 50 to 1000 nm and heights from 50 to 500 nm, each with a precision of few nanometers. The fabricated nanowaveguides are tested in an optical characterization experiment showing efficient second-harmonic generation. PMID- 26684216 TI - The Casein Kinase 2-Dependent Phosphorylation of NS5A Domain 3 from Hepatitis C Virus Followed by Time-Resolved NMR Spectroscopy. AB - Hepatitis C virus (HCV) chronically affects millions of individuals worldwide. The HCV nonstructural protein 5A (NS5A) plays a critical role in the viral assembly pathway. Domain 3 (D3) of NS5A is an unstructured polypeptide responsible for the interaction with the core particle assembly structure. Casein kinase 2 (CK2) phosphorylates NS5A-D3 at multiple sites that have mostly been predicted and only observed indirectly. In order to identify the CK2-dependent phosphorylation sites, we monitored the reaction between NS5A-D3 and CK2 in vitro by time-resolved NMR. We unambiguously identified four serine residues as substrates of CK2. The apparent rate constant for each site was determined from the reaction curves. Ser408 was quickly phosphorylated, whereas the three other serine residues reacted more slowly. These results provide a starting point from which to elucidate the role of phosphorylation in the mechanisms of viral assembly-and in the modulation of the viral activity-at the molecular level. PMID- 26684218 TI - Colloidal Properties of Nanoerythrosomes Derived from Bovine Red Blood Cells. AB - Liposomes are nanoscale containers that are typically synthesized from lipids using a high-shear process such as extrusion or sonication. While liposomes are extensively used in drug delivery, they do suffer from certain problems including limited colloidal stability and short circulation times in the body. As an alternative to liposomes, we explore a class of container structures derived from erythrocytes (red blood cells). The procedure involves emptying the inner contents of these cells (specifically hemoglobin) and resuspending the empty structures in buffer, followed by sonication. The resulting structures are termed nanoerythrosomes (NERs), i.e., they are membrane-covered nanoscale containers, much like liposomes. Cryo-transmission electron microscopy (cryo-TEM) and small angle neutron scattering (SANS) are employed for the first time to study these NERs. The results reveal that the NERs are discrete spheres (~110 nm diameter) with a unilamellar membrane of thickness ~4.5 nm. Remarkably, the biconcave disc like shape of erythrocytes is also exhibited by the NERs under hypertonic conditions. Moreover, unlike typical liposomes, NERs show excellent colloidal stability in both buffer as well as in serum at room temperature, and are also able to withstand freeze-thaw cycling. We have explored the potential for using NERs as colloidal vehicles for targeted delivery. Much like conventional liposomes, NER membranes can be decorated with fluorescent or other markers, solutes can be encapsulated in the cores of the NERs, and NERs can be targeted to specifically bind to mammalian cells. Our study shows that NERs are a promising and versatile class of nanostructures. NERs that are harvested from a patient's own blood and reconfigured for nanomedicine can potentially offer several benefits including biocompatibility, minimization of immune response, and extended circulation time in the body. PMID- 26684219 TI - Application of an Artificial Neural Network to the Prediction of OH Radical Reaction Rate Constants for Evaluating Global Warming Potential. AB - Rate constants for reactions of chemical compounds with hydroxyl radical are a key quantity used in evaluating the global warming potential of a substance. Experimental determination of these rate constants is essential, but it can also be difficult and time-consuming to produce. High-level quantum chemistry predictions of the rate constant can suffer from the same issues. Therefore, it is valuable to devise estimation schemes that can give reasonable results on a variety of chemical compounds. In this article, the construction and training of an artificial neural network (ANN) for the prediction of rate constants at 298 K for reactions of hydroxyl radical with a diverse set of molecules is described. Input to the ANN consists of counts of the chemical bonds and bends present in the target molecule. The ANN is trained using 792 (*)OH reaction rate constants taken from the NIST Chemical Kinetics Database. The mean unsigned percent error (MUPE) for the training set is 12%, and the MUPE of the testing set is 51%. It is shown that the present methodology yields rate constants of reasonable accuracy for a diverse set of inputs. The results are compared to high-quality literature values and to another estimation scheme. This ANN methodology is expected to be of use in a wide range of applications for which (*)OH reaction rate constants are required. The model uses only information that can be gathered from a 2D representation of the molecule, making the present approach particularly appealing, especially for screening applications. PMID- 26684220 TI - Discovering the knowledge creation process of an expert group in women-friendly policy: The policy case of Seoul City. AB - This research explores how expert knowledge is created in the process of women friendly policy making, based on actor network theory (ANT). To address this purpose, this study uses the "Women's Happiness in the City of Seoul" policy initiated by the local government of Seoul as one example of policy development. Research findings demonstrate that knowledge creation in expert groups followed the four stages suggested by ANT. In addition, this study found that various types of knowledge emerged from individual experts. This research elucidates the process of knowledge creation and its meanings for women-friendly policy. PMID- 26684221 TI - Somatic assessments of 120 Swedish children taken into care reveal large unmet health and dental care needs. AB - AIM: For decades, non-Nordic countries have consistently reported high rates of somatic health problems among children placed in care by the authorities. This study examined the unmet health and dental care needs of Swedish children in foster and residential care. METHODS: The health of 120 consecutive children aged 0-17 years, who had recently been placed in foster or residential care in one Swedish region, was assessed by an experienced paediatrician using patient records, their medical history and a physical examination. RESULTS: Following the assessments, 51% of the subjects received at least one referral to a specialist or to primary care, either for a previously undetected medical condition or for a follow-up of a previously detected condition noted in their patient records. The study showed that 40% of the girls and 33% of boys were overweight and completed vaccination rates were only 86% for children up to the age of six and 68% for 7- to 17-year-olds. Half of the 7- to 17-year-olds had untreated dental decay. CONCLUSION: Our study revealed a large unmet need for health and dental care interventions among children placed in foster care and residential care and a systematic strategy is required to address those needs. PMID- 26684222 TI - Quantum simulations of lattice gauge theories using ultracold atoms in optical lattices. AB - Can high-energy physics be simulated by low-energy, non-relativistic, many-body systems such as ultracold atoms? Such ultracold atomic systems lack the type of symmetries and dynamical properties of high energy physics models: in particular, they manifest neither local gauge invariance nor Lorentz invariance, which are crucial properties of the quantum field theories which are the building blocks of the standard model of elementary particles. However, it turns out, surprisingly, that there are ways to configure an atomic system to manifest both local gauge invariance and Lorentz invariance. In particular, local gauge invariance can arise either as an effective low-energy symmetry, or as an exact symmetry, following from the conservation laws in atomic interactions. Hence, one could hope that such quantum simulators may lead to a new type of (table-top) experiments which will be used to study various QCD (quantum chromodynamics) phenomena, such as the confinement of dynamical quarks, phase transitions and other effects, which are inaccessible using the currently known computational methods. In this report, we review the Hamiltonian formulation of lattice gauge theories, and then describe our recent progress in constructing the quantum simulation of Abelian and non-Abelian lattice gauge theories in 1 + 1 and 2 + 1 dimensions using ultracold atoms in optical lattices. PMID- 26684238 TI - Bone morphogenetic protein 4 regulates microRNA expression in breast cancer cell lines in diverse fashion. AB - Bone morphogenetic protein 4 (BMP4) is a remarkably powerful inhibitor of breast cancer cell proliferation, but it is also able to induce breast cancer cell migration in certain cellular contexts. Previous data demonstrate that BMP4 controls the transcription of a variety of protein-coding genes, but not much is known about microRNAs (miRNA) regulated by BMP4. To address this question, miRNA expression profiles following BMP4 treatment were determined in one mammary epithelial and seven breast cancer cell lines using microarrays. While the analysis revealed an extensive variation in differentially expressed miRNA across cell lines, four miRNAs (miR-16-5p, miR-106b-5p, miR-23a-3p, and miR-23b-3p) were commonly induced in a subset of breast cancer cells upon BMP4 treatment. Inhibition of their expression demonstrated an increase in BT-474 cell number, indicating that they possess tumor suppressive properties. However, with the exception of miR-106b-5p, these effects were independent of BMP4 treatment. Scratch assay with miR-16-5p and miR-106b-5p inhibitors on BMP4-treated MDA-MB 231 cells resulted in enhanced cell migration, suggesting that these miRNAs are engaged in BMP4-induced motility. Taken together, we have for the first time characterized the BMP4-induced miRNA expression profiles in breast cancer cell lines, showing that induced miRNAs contribute to the fine-tuning of proliferation and migration phenotypes. PMID- 26684239 TI - Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b. AB - In melanoma, the adaptative cell response to BRAF inhibitors includes altered patterns of cytokine production contributing to tumor progression and drug resistance. Among the factors produced by PLX4032-resistant melanoma cell lines, CCL2 was higher compared to the sensitive parental cell lines and increased upon drug treatment. CCL2 acted as an autocrine growth factor for melanoma cells, stimulating the proliferation and resistance to apoptosis. In patients, CCL2 is detected in melanoma cells in tumors and in plasma at levels that correlate with tumor burden and lactate dehydrogenase. Vemurafenib treatment increased the CCL2 levels in plasma, whereas the long-term clinical response was associated with low CCL2 levels.Increased CCL2 production was associated with miRNA deregulation in the resistant cells. miR-34a, miR-100 and miR-125b showed high expression in both resistant cells and in tumor biopsies that were obtained from treated patients, and they were involved in the control of cell proliferation and apoptosis. Inhibition of CCL2 and of the selected miRNAs restored both the cell apoptosis and the drug efficacy in resistant melanoma cells. Therefore, CCL2 and miRNAs are potential prognostic factors and attractive targets for counteracting treatment resistance in metastatic melanoma. PMID- 26684240 TI - Identification of the BRAF V600E mutation in gastroenteropancreatic neuroendocrine tumors. AB - Genomic profiles of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are still insufficiently understood, and the genetic alterations associated with drug responses have not been studied. Here, we performed whole exome sequencing of 12 GEP-NETs from patients enrolled in a nonrandomized, open-labeled, single-center phase II study for pazopanib, and integrated our results with previously published results on pancreas (n = 12) and small intestine NETs (n = 50). The mean numbers of somatic mutations in each case varied widely from 20 to 4682. Among 12 GEP-NETs, eight showed mutations of more than one cancer-related gene, including TP53, CNBD1, RB1, APC, BCOR, BRAF, CTNNB1, EGFR, EP300, ERBB3, KDM6A, KRAS, MGA, MLL3, PTEN, RASA1, SMARCB1, SPEN, TBC1D12, and VHL. TP53 was recurrently mutated in three cases, whereas CNBD1 and RB1 mutations were identified in two cases. Three GEP-NET patients with TP53 mutations demonstrated a durable response and one small intestinal grade (G) 1 NET patient with BRAF V600E mutation showed progression after pazopanib treatment. We found BRAF V600E (G1 NET from rectum and two G3 NETs from colon) and BRAF G593S (G2 NET from pancreas) missense mutations (9.1%) in an independent cohort of 44 GEP-NETs from the rectum (n = 26), colon (n = 7), pancreas (n = 4), small intestine (n = 3), stomach (n = 3) and appendix (n = 1) by Sanger sequencing. All tumor specimens were obtained before chemotherapy. In conclusion, BRAF V600E mutation is likely to result in resistance to pazopanib but may be a potentianally actionable mutation in metastatic GEP-NETs patients. PMID- 26684241 TI - miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma. AB - Metastasis is one of the causes of cancer death. Functions and mechanisms of microRNAs (miRNAs) involved in hepatocellular carcinoma (HCC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in MHCC-97L, MHCC-97H and HCC-LM3 cells with gradually increasing metastatic potential to disclose crucial miRNAs involved in HCC metastasis. miR-192 expression decreased and negatively correlated with vascular invasion in HCC specimens. Gain and loss of function studies revealed that miR-192 significantly suppressed metastasis of HCC cells in vitro and in vivo. Solute carrier family 39 member 6 (SLC39A6) was identified as a direct and functional target of miR-192. In addition, SLC39A6 negatively correlated with miR-192 in HCC samples and promoted HCC cell migration and invasion. Moreover, miR-192 decreased SLC39A6 expression, subsequently downregulating SNAIL and upregulating E-cadherin expression. Suppression of migration and invasion caused by miR-192 overexpression was alleviated by exogenous Snail expression. Intriguingly, lower miR-192 expression and higher SLC39A6 expression significantly contributed to poorer outcomes in HCC patients. Multivariate analysis indicated that miR-192 was an independent and significant predictor of HCC patient overall survival. In conclusion, we newly determined that miR-192 targeted the SLC39A6/SNAIL pathway to reduce tumor metastasis in HCC cells. This axis provided insights into the mechanism underlying miRNA regulation of HCC metastasis and a novel therapeutic target for HCC treatment. PMID- 26684243 TI - Acupuncture for Ischemic Stroke, Music for Anxiety in Mechanical Ventilation, Essential Fatty Acids for Depression, Mindfulness Meditation for Sleep in Older Adults, Tripterygium wilfordii for Rheumatoid Arthritis. PMID- 26684242 TI - TGF-beta/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis. AB - Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of alpha-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-beta/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-beta1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-beta/Smad3 signalling. PMID- 26684244 TI - Metastatic Adenoid Cystic Carcinoma of the Breast. PMID- 26684245 TI - An optimization framework to maximize signal-to-noise ratio in simultaneous multi slice body imaging. AB - Parallel imaging is essential for the acceleration of abdominal and pelvic 2D multi-slice imaging, in order to reduce scan time and mitigate motion artifacts. Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration (CAIPIRINHA) accelerated imaging has been shown to increase the signal-to-noise ratio (SNR) significantly compared with in-plane parallel imaging with similar acceleration. We hypothesize that for CAIPIRINHA-accelerated abdominal imaging the consistency of image quality and SNR is more difficult to achieve due to the subject-specific coil sensitivity profiles, caused by (1) flexible coil placement; (2) variations in anatomy; and (3) variations in scan coverage along the superior-inferior direction. To test this, a mathematical framework is introduced that calculates the (retained) SNR for in-plane and simultaneous multi slice (SMS)-accelerated acquisitions. Moreover, this framework was used to optimize the sampling pattern by maximizing the local SNR within a region of interest (ROI) through non-linear, RF-induced CAIPIRINHA slice shifts. The framework was evaluated on 14 healthy subjects and the optimized sampling pattern was compared with in-plane acceleration and CAIPIRINHA acceleration with linear slice shifts, which are primarily used in brain imaging. We demonstrate that the field of view (FOV) in the superior-inferior direction, the coil positioning and the individual anatomy have a large impact on the image SNR (changes up to 50% for varying coil positions and 40% differences between subjects) and image artifacts for simultaneous multi-slice acceleration. Consequently, sampling patterns have to be optimized for acquisitions employing different FOVs and ideally on an individual basis. Optimization of the sampling pattern, which exploits non-linear shifts between slices, showed a considerable SNR increase (10 30%) for higher acceleration factors. The framework outlined in this article can be used to optimize sampling patterns for a broad range of accelerated body acquisitions on an individual basis. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26684247 TI - Methylene blue not ferrocene: Optimal reporters for electrochemical detection of protease activity. AB - Electrochemical peptide-based biosensors are attracting significant attention for the detection and analysis of proteins. Here we report the optimisation and evaluation of an electrochemical biosensor for the detection of protease activity using self-assembled monolayers (SAMs) on gold surfaces, using trypsin as a model protease. The principle of detection was the specific proteolytic cleavage of redox-tagged peptides by trypsin, which causes the release of the redox reporter, resulting in a decrease of the peak current as measured by square wave voltammetry. A systematic enhancement of detection was achieved through optimisation of the properties of the redox-tagged peptide; this included for the first time a side-by-side study of the applicability of two of the most commonly applied redox reporters used for developing electrochemical biosensors, ferrocene and methylene blue, along with the effect of changing both the nature of the spacer and the composition of the SAM. Methylene blue-tagged peptides combined with a polyethylene-glycol (PEG) based spacer were shown to be the best platform for trypsin detection, leading to the highest fidelity signals (characterised by the highest sensitivity (signal gain) and a much more stable background than that registered when using ferrocene as a reporter). A ternary SAM (T-SAM) configuration, which included a PEG-based dithiol, minimised the non-specific adsorption of other proteins and was sensitive towards trypsin in the clinically relevant range, with a Limit of Detection (LoD) of 250pM. Kinetic analysis of the electrochemical response with time showed a good fit to a Michaelis-Menten surface cleavage model, enabling the extraction of values for kcat and KM. Fitting to this model enabled quantitative determination of the solution concentration of trypsin across the entire measurement range. Studies using an enzyme inhibitor and a range of real world possible interferents demonstrated a selective response to trypsin cleavage. This indicates that a PEG-based peptide, employing methylene blue as redox reporter, and deposited on an electrode as a ternary SAM configuration, is a suitable platform to develop clinically-relevant and quantitative electrochemical peptide-based protease biosensing. PMID- 26684246 TI - Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury. AB - Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (<=24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34 degrees C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post traumatic nonconvulsive seizures. In the later phase of the injury (7-21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13-17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple domains that were evident days/weeks beyond the cooling duration and in the absence of overt adverse effects. These "proof-of-concept" results suggest that SBC may provide an attractive neuroprotective approach for clinical considerations. PMID- 26684248 TI - Increased consumption and vasodilatory effect of nitrite during exercise. AB - This study investigated the effects of aerobic-to-anaerobic exercise on nitrite stores in the human circulation and evaluated the effects of systemic nitrite infusion on aerobic and anaerobic exercise capacity and hemodynamics. Six healthy volunteers were randomized to receive sodium nitrite or saline for 70 min in two separate occasions in an exercise study. Subjects cycled on an upright electronically braked cycle ergometer 30 min into the infusion according to a ramp protocol designed to attain exhaustion in 10 min. They were allowed to recover for 30 min thereafter. The changes of whole blood nitrite concentrations over the 70-min study period were analyzed by pharmacokinetic modeling. Longitudinal measurements of hemodynamic and clinical variables were analyzed by fitting nonparametric regression spline models. During exercise, nitrite consumption/elimination rate was increased by ~137%. Cardiac output (CO), mean arterial pressure (MAP), and pulmonary artery pressure (PAP) were increased, but smaller elevation of MAP and larger increases of CO and PAP were found during nitrite infusion compared with placebo control. The higher CO and lower MAP during nitrite infusion were likely attributed to vasodilation and a trend toward decrease in systemic vascular resistance. In contrast, there were no significant changes in mean pulmonary artery pressures and pulmonary vascular resistance. These findings, together with the increased consumption of nitrite and production of iron-nitrosyl-hemoglobin during exercise, support the notion of nitrite conversion to release NO resulting in systemic vasodilatation. However, at the dosing used in this protocol achieving micromolar plasma concentrations of nitrite, exercise capacity was not enhanced, as opposed to other reports using lower dosing. PMID- 26684250 TI - Positioning of extracellular loop 1 affects pore gating of the cystic fibrosis transmembrane conductance regulator. AB - The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a chloride ion channel, the dysfunction of which directly leads to the life-shortening disease CF. Extracellular loop 1 (ECL1) of CFTR contains several residues involved in stabilizing the open state of the channel; some, including D110, are sites of disease-associated gating mutations. Structures from related proteins suggest that the position of CFTR's extracellular loops may change considerably during gating. To better understand the roles of ECL1 in CFTR function, we utilized functional cysteine cross-linking to determine the effects of modulation of D110C-CFTR and of a double mutant of D110C with K892C in extracellular loop 4 (ECL4). The reducing agent DTT elicited a large potentiation of the macroscopic conductance of D110C/K892C-CFTR, likely due to breakage of a spontaneous disulfide bond between C110 and C892. DTT-reduced D110C/K892C-CFTR was rapidly inhibited by binding cadmium ions with high affinity, suggesting that these residues frequently come in close proximity in actively gating channels. Effects of DTT and cadmium on modulation of pore gating were demonstrated at the single channel level. Finally, disulfided D110C/K892C-CFTR channels were found to be less sensitive than wild-type or DTT-treated D110C/K892C-CFTR channels to stimulation by IBMX, suggesting an impact of this conformational restriction on channel activation by phosphorylation. The results are best explained in the context of a model of CFTR gating wherein stable channel opening requires correct positioning of functional elements structurally influenced by ECL1. PMID- 26684249 TI - TREM-1-accentuated lung injury via miR-155 is inhibited by LP17 nanomedicine. AB - Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. Synergy between TREM-1 and Toll-like receptor amplifies the inflammatory response; however, the mechanisms by which TREM-1 accentuates inflammation are not fully understood. In this study, we investigated the role of TREM-1 in a model of LPS-induced lung injury and neutrophilic inflammation. We show that TREM-1 is induced in lungs of mice with LPS-induced acute neutrophilic inflammation. TREM-1 knockout mice showed an improved survival after lethal doses of LPS with an attenuated inflammatory response in the lungs. Deletion of TREM-1 gene resulted in significantly reduced neutrophils and proinflammatory cytokines and chemokines, particularly IL-1beta, TNF-alpha, and IL-6. Physiologically deletion of TREM-1 conferred an immunometabolic advantage with low oxygen consumption rate (OCR) sparing the respiratory capacity of macrophages challenged with LPS. Furthermore, we show that TREM-1 deletion results in significant attenuation of expression of miR-155 in macrophages and lungs of mice treated with LPS. Experiments with antagomir-155 confirmed that TREM-1-mediated changes were indeed dependent on miR 155 and are mediated by downregulation of suppressor of cytokine signaling-1 (SOCS-1) a key miR-155 target. These data for the first time show that TREM-1 accentuates inflammatory response by inducing the expression of miR-155 in macrophages and suggest a novel mechanism by which TREM-1 signaling contributes to lung injury. Inhibition of TREM-1 using a nanomicellar approach resulted in ablation of neutrophilic inflammation suggesting that TREM-1 inhibition is a potential therapeutic target for neutrophilic lung inflammation and acute respiratory distress syndrome (ARDS). PMID- 26684251 TI - Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells. AB - Airway remodeling is a hallmark feature of asthma and chronic obstructive pulmonary disease. Clinical studies and animal models have demonstrated increased airway smooth muscle (ASM) mass, and ASM thickness is correlated with severity of the disease. Current medications control inflammation and reverse airway obstruction effectively but have limited effect on remodeling. Recently we identified the expression of bitter taste receptors (TAS2R) on ASM cells, and activation with known TAS2R agonists resulted in ASM relaxation and bronchodilation. These studies suggest that TAS2R can be used as new therapeutic targets in the treatment of obstructive lung diseases. To further establish their effectiveness, in this study we aimed to determine the effects of TAS2R agonists on ASM growth and promitogenic signaling. Pretreatment of healthy and asthmatic human ASM cells with TAS2R agonists resulted in a dose-dependent inhibition of ASM proliferation. The antimitogenic effect of TAS2R ligands was not dependent on activation of protein kinase A, protein kinase C, or high/intermediate conductance calcium-activated K(+) channels. Immunoblot analyses revealed that TAS2R agonists inhibit growth factor-activated protein kinase B phosphorylation without affecting the availability of phosphatidylinositol 3,4,5-trisphosphate, suggesting TAS2R agonists block signaling downstream of phosphatidylinositol 3 kinase. Furthermore, the antimitogenic effect of TAS2R agonists involved inhibition of induced transcription factors (activator protein-1, signal transducer and activator of transcription-3, E2 factor, nuclear factor of activated T cells) and inhibition of expression of multiple cell cycle regulatory genes, suggesting a direct inhibition of cell cycle progression. Collectively, these findings establish the antimitogenic effect of TAS2R agonists and identify a novel class of receptors and signaling pathways that can be targeted to reduce or prevent airway remodeling as well as bronchoconstriction in obstructive airway disease. PMID- 26684253 TI - Frank Low and the first images of the ultrastructure of the pulmonary blood-gas barrier. AB - Frank N. Low (1911-1998) has the distinction of publishing the first electron micrographs showing the ultrastructure of the pulmonary capillary and particularly the blood-gas barrier. This work in 1952 and 1953 was enabled by the progress in fixation and staining of tissue made by George Palade and was part of the very rapid advance in electron microscopy during the previous 25 years. Low's micrographs clearly showed the three layers of the blood-gas barrier: capillary endothelium, extracellular matrix, and alveolar epithelium. The images immediately resolved the debate about the composition of the blood-gas barrier that had been raging for 100 years. The first published micrographs were rather poor, but the quality rapidly improved and a major event was the first electron micrograph of the human blood-gas barrier published in 1953. These images had an enormous influence on the development of pulmonary physiology and biology. For example, for the first time it became clear that the barrier separating the blood from the alveolar gas was vanishingly thin. The discovery of the extracellular matrix layer ultimately clarified how this barrier, despite its extraordinary thinness, was sufficiently strong to avoid mechanical failure. Despite the major advances made by Low, his name is almost unknown in pulmonary physiology and biology, and perhaps this tribute will help to give him his due. PMID- 26684252 TI - Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors. AB - Influenza causes an acute infection characterized by virus replication in respiratory epithelial cells. The severity of influenza and other respiratory diseases changes over the life course and during pregnancy in women, suggesting that sex steroid hormones, such as estrogens, may be involved. Using primary, differentiated human nasal epithelial cell (hNEC) cultures from adult male and female donors, we exposed cultures to the endogenous 17beta-estradiol (E2) or select estrogen receptor modulators (SERMs) and then infected cultures with a seasonal influenza A virus (IAV) to determine whether estrogenic signaling could affect the outcome of IAV infection and whether these effects were sex dependent. Estradiol, raloxifene, and bisphenol A decreased IAV titers in hNECs from female, but not male, donors. The estrogenic decrease in viral titer was dependent on the genomic estrogen receptor-2 (ESR2) as neither genomic ESR1 nor nongenomic GPR30 was expressed in hNEC cultures and addition of the genomic ER antagonist ICI 182,780 reversed the antiviral effects of E2. Treatment of hNECs with E2 had no effect on interferon or chemokine secretion but significantly downregulated cell metabolic processes, including genes that encode for zinc finger proteins, many of which contain estrogen response elements in their promoters. These data provide novel insights into the cellular and molecular mechanisms of how natural and synthetic estrogens impact IAV infection in respiratory epithelial cells derived from humans. PMID- 26684254 TI - [Diagram of diagnosis and management of type 2 diabetes mellitus. Update]. PMID- 26684255 TI - Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects. AB - OBJECTIVES: Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. METHODS: A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 +/- 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. RESULTS: Compared with subjects with a total bilirubin (TB) concentration of <10.0 MUmol/L, those with a TB concentration of >17.1 MUmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. CONCLUSIONS: High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. PMID- 26684256 TI - A Gesture Recognition System for Detecting Behavioral Patterns of ADHD. AB - We present an application of gesture recognition using an extension of dynamic time warping (DTW) to recognize behavioral patterns of attention deficit hyperactivity disorder (ADHD). We propose an extension of DTW using one-class classifiers in order to be able to encode the variability of a gesture category, and thus, perform an alignment between a gesture sample and a gesture class. We model the set of gesture samples of a certain gesture category using either Gaussian mixture models or an approximation of convex hulls. Thus, we add a theoretical contribution to classical warping path in DTW by including local modeling of intraclass gesture variability. This methodology is applied in a clinical context, detecting a group of ADHD behavioral patterns defined by experts in psychology/psychiatry, to provide support to clinicians in the diagnose procedure. The proposed methodology is tested on a novel multimodal dataset (RGB plus depth) of ADHD children recordings with behavioral patterns. We obtain satisfying results when compared to standard state-of-the-art approaches in the DTW context. PMID- 26684257 TI - Cluster Prototypes and Fuzzy Memberships Jointly Leveraged Cross-Domain Maximum Entropy Clustering. AB - The classical maximum entropy clustering (MEC) algorithm usually cannot achieve satisfactory results in the situations where the data is insufficient, incomplete, or distorted. To address this problem, inspired by transfer learning, the specific cluster prototypes and fuzzy memberships jointly leveraged (CPM-JL) framework for cross-domain MEC (CDMEC) is firstly devised in this paper, and then the corresponding algorithm referred to as CPM-JL-CDMEC and the dedicated validity index named fuzzy memberships-based cross-domain difference measurement (FM-CDDM) are concurrently proposed. In general, the contributions of this paper are fourfold: 1) benefiting from the delicate CPM-JL framework, CPM-JL-CDMEC features high-clustering effectiveness and robustness even in some complex data situations; 2) the reliability of FM-CDDM has been demonstrated to be close to well-established external criteria, e.g., normalized mutual information and rand index, and it does not require additional label information. Hence, using FM-CDDM as a dedicated validity index significantly enhances the applicability of CPM-JL CDMEC under realistic scenarios; 3) the performance of CPM-JL-CDMEC is generally better than, at least equal to, that of MEC because CPM-JL-CDMEC can degenerate into the standard MEC algorithm after adopting the proper parameters, and which avoids the issue of negative transfer; and 4) in order to maximize privacy protection, CPM-JL-CDMEC employs the known cluster prototypes and their associated fuzzy memberships rather than the raw data in the source domain as prior knowledge. The experimental studies thoroughly evaluated and demonstrated these advantages on both synthetic and real-life transfer datasets. PMID- 26684258 TI - Robust Extreme Learning Machine With its Application to Indoor Positioning. AB - The increasing demands of location-based services have spurred the rapid development of indoor positioning system and indoor localization system interchangeably (IPSs). However, the performance of IPSs suffers from noisy measurements. In this paper, two kinds of robust extreme learning machines (RELMs), corresponding to the close-to-mean constraint, and the small-residual constraint, have been proposed to address the issue of noisy measurements in IPSs. Based on whether the feature mapping in extreme learning machine is explicit, we respectively provide random-hidden-nodes and kernelized formulations of RELMs by second order cone programming. Furthermore, the computation of the covariance in feature space is discussed. Simulations and real-world indoor localization experiments are extensively carried out and the results demonstrate that the proposed algorithms can not only improve the accuracy and repeatability, but also reduce the deviation and worst case error of IPSs compared with other baseline algorithms. PMID- 26684259 TI - Distributed Synchronization Control of Multiagent Systems With Unknown Nonlinearities. AB - This paper revisits the distributed adaptive control problem for synchronization of multiagent systems where the dynamics of the agents are nonlinear, nonidentical, unknown, and subject to external disturbances. Two communication topologies, represented, respectively, by a fixed strongly-connected directed graph and by a switching connected undirected graph, are considered. Under both of these communication topologies, we use distributed neural networks to approximate the uncertain dynamics. Decentralized adaptive control protocols are then constructed to solve the cooperative tracker problem, the problem of synchronization of all follower agents to a leader agent. In particular, we show that, under the proposed decentralized control protocols, the synchronization errors are ultimately bounded, and their ultimate bounds can be reduced arbitrarily by choosing the control parameter appropriately. Simulation study verifies the effectiveness of our proposed protocols. PMID- 26684260 TI - First aid management for chemical burns: Where is the evidence? PMID- 26684261 TI - Soluble B-cell activation marker of sCD27 and sCD30 and future risk of B-cell lymphomas: A nested case-control study and meta-analyses. AB - Prediagnostic serum/plasma concentrations of B-cell activation markers have been associated with future risk of B-cell lymphomas (BCL) in HIV-infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case-control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta-analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR = 0.86, 1.53, 1.76, for the 2nd-4th quartiles respectively, p trend = 0.01). Similar increased risks were observed for diffuse large B-cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR = 0.90, 1.26, 1.65 for the 2nd-4th quartiles, respectively, p trend = 0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of "other BCL" subtypes. Our findings involving sCD30 were confirmed within our meta-analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B-cell stimulation might be an important mechanism involved in B-cell lymphomagenesis both in HIV-infected and in the general population. PMID- 26684262 TI - New pharmacotherapy options for multiple myeloma. AB - INTRODUCTION: Novel agents and the availability of autologous stem-cell transplantation have revolutionized the treatment of patients with multiple myeloma. First-generation novel agents namely thalidomide, lenalidomide, and bortezomib have significantly improved response and survival of patients. Second generation novel agents such as pomalidomide, carfilzomib, and monoclonal antibodies are being tested both in the newly diagnosed and relapse settings, and results are promising. AREAS COVERED: In this review article, the main results derived from Phase III trials with thalidomide, lenalidomide, and bortezomib for the treatment of myeloma patients, both at diagnosis and at relapse, are summarized. Data about second-generation novel agents such as pomalidomide and carfilzomib are also reported. Newer effective drugs currently under investigation and the promising results with monoclonal antibodies are described. EXPERT OPINION: The availability of new effective drugs has considerably increased the treatment options for myeloma patients. A sequential approach including induction, transplantation (when possible), consolidation, and maintenance is an optimal strategy to achieve disease control and prolong survival. Despite these improvements, the best combination, the optimal sequence, and the proper target of newer drugs need to be defined. PMID- 26684263 TI - Neurobehavioral alterations plus transcriptional changes of the heat shock protein 90 and hypoxia inducible factor-1alpha in the crucian carp exposed to copper. AB - The various physiological alterations caused by copper (Cu) exposure in fish have attracted great interests toward neuronal strategies against Cu toxicity. Here, neurobehavioral activities (including anxiety-like behaviors) and transcriptional levels of heat shock protein (Hsp)90 and hypoxia inducible factor-1alpha (HIF 1alpha) were evaluated in the crucian carp (Carassius carassius) treated with nominal sub-lethal higher (1.45mg/L) and lower (0.30mg/L) concentrations of CuCl2. Both concentrations accounted for diminished swimming speed and food intake plus a strong preference for the dark side of the light/dark apparatus together with a reduction of crossings between the two compartments with respect to controls. Contextually, Hsp90 and HIF-1alpha transcripts were largely down- and up-regulated, respectively, in some brain areas such as in the medial part of the dorsal telencephalon (Dm, -52%) and in the ventral part of the ventral telencephalon (Vv, +68%). When carps were transferred to CuCl2-free water, some behaviors were rescued especially for fish previously exposed to 0.30mg/L concentration. In this same condition, Hsp90 mRNA levels were recuperated (-94%) in the medial preglomerular nucleus (NPGm) with respect to exposed fish while HIF 1alpha mRNA was mostly down-regulated in telencephalic stations. Moreover, recovery capacities of this extraordinary resistant fish was exhibited by evident reductions (-80%) of the dark argyrophilic granules such as in the ventral telencephalon (VTel). Overall, our results point to interesting responses against Cu toxicity involving Hsp90 and HIF-1alpha transcripts that may constitute early indicators of environmental stressors leading to the repair of metal-induced damages in fish with notable brain plasticity properties. PMID- 26684264 TI - Reply to Letter to the Editor: Cognitive therapy in Sick Building Syndrome: Myths, beliefs or evidence. PMID- 26684265 TI - Intensive cycle ergometer training improves gait speed and endurance in patients with Parkinson's disease: A comparison with treadmill training. AB - PURPOSE: Cycle ergometer training improves gait in the elderly, but its effect in patients with Parkinson's disease (PD) is not completely known. METHODS: Twenty nine PD inpatients were randomized to treadmill (n = 13, PD-T) or cycle ergometer (n = 16, PD-C) training for 3 weeks, 1 hour/day. Outcome measures were distance travelled during the 6-min walking test (6MWT), spatio-temporal variables of gait assessed by baropodometry, the Timed Up and Go (TUG) duration, the balance score through the Mini-BESTest, and the score of the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Sex, age, body mass index, disease duration, Hoehn-Yahr staging, comorbidity and medication did not differ between groups. At end of training, ANCOVA showed significant improvement, of similar degree, in both groups for 6MWT, speed, step length and cadence of gait, TUG, Mini-BESTest and UPDRS. CONCLUSIONS: This pilot study shows that cycle ergometer training improves walking parameters and reduces clinical signs of PD, as much as treadmill training does. Gait velocity is accompanied by step lengthening, making the gait pattern close to that of healthy subjects. Cycle ergometer is a valid alternative to treadmill for improving gait in short term in patients with PD. PMID- 26684266 TI - Efficacy of cognitive intervention in stroke: A long road ahead. AB - Numerous studies have been conducted discussing the importance and effectiveness of cognitive interventions for stroke-related cognitive impairments. Definite conclusions, however, are yet to be established. An extensive literature and database search was executed to summarize the existing evidence from high-quality randomized clinical trials on the effects of cognitive intervention and feasibility of this approach in stroke patients. Out of 507 identified studies, after thorough inspection, only three randomized clinical trials, with low risk of bias, met the established criteria and were included in the following meta analysis. No significant effects of cognitive intervention in any of the analyzed outcomes were observed with feasibility analyzes displaying high rates of completion and adherence.The following study suggests a lack of sufficient evidence to support or refute the efficacy of cognitive intervention in stroke patients. However, these results should be interpreted with caution. Additionally, serious efforts must be made to improve the quality of empirical studies in the field. In sum, the quality of methodological techniques in the field were inspected in hopes of contributing to further development of this therapeutic approach. PMID- 26684268 TI - Amorphous SiO2 NP-Incorporated Poly(vinylidene fluoride) Electrospun Nanofiber Membrane for High Flux Forward Osmosis Desalination. AB - Novel amorphous silica nanoparticle-incorporated poly(vinylidine fluoride) electrospun nanofiber mats are introduced as effective membranes for forward osmosis desalination technology. The influence of the inorganic nanoparticle content on water flux and salt rejection was investigated by preparing electrospun membranes with 0, 0.5, 1, 2, and 5 wt % SiO2 nanoparticles. A laboratory-scale forward osmosis cell was utilized to validate the performance of the introduced membranes using fresh water as a feed and different brines as draw solution (0.5, 1, 1.5, and 2 M NaCl). The results indicated that the membrane embedding 0.5 wt % displays constant salt rejection of 99.7% and water flux of 83 L m(-2) h(-1) with 2 M NaCl draw solution. Moreover, this formulation displayed the lowest structural parameter (S = 29.7 MUm), which represents approximately 69% reduction compared to the pristine membrane. Moreover, this study emphasizes the capability of the electrospinning process in synthesizing effective membranes as the observed water flux and average salt rejection of the pristine poly(vinylidine fluoride) membrane was 32 L m(-2) h(-1) (at 2 M NaCl draw solution) and 99%, respectively. On the other hand, increasing the inorganic nanoparticles to 5 wt % showed negative influence on the salt rejection as the observed salt flux was 1651 mol m(-2) h(-1). Besides the aforementioned distinct performance, studies of the mechanical properties, porosity, and wettability concluded that the introduced membranes are effective for forward osmosis desalination technology. PMID- 26684267 TI - Glaucoma -state of the art and perspectives on treatment. AB - Glaucoma is a chronic optic neuropathy characterized by progressive damage to the optic nerve, death of retinal ganglion cells and ultimately visual field loss. It is one of the leading causes of irreversible loss of vision worldwide. The most important trigger of glaucomatous damage is elevated eye pressure, and the current standard approach in glaucoma therapy is reduction of intraocular pressure (IOP). However, despite the use of effective medications or surgical treatment leading to lowering of IOP, progression of glaucomatous changes and loss of vision among patients with glaucoma is common. Therefore, it is critical to prevent vision loss through additional treatment. To implement such treatment(s), it is imperative to identify pathophysiological changes in glaucoma and develop therapeutic methods taking into account neuroprotection. Currently, there is no method of neuroprotection with long-term proven effectiveness in the treatment of glaucoma. Among the most promising molecules shown to protect the retina and optic nerve are neurotrophic factors. Thus, the current focus is on the development of safe and non-invasive methods for the long-term elevation of the intraocular level of neurotrophins through advanced gene therapy and topical eye treatment and on the search for selective agonists of neurotrophin receptors affording more efficient neuroprotection. PMID- 26684269 TI - Diagnostic overview of the illegal trade in primates and law enforcement in Peru. AB - Peru has one of the richest primate faunas of any country. The illegal trade in wild primates is one of the largest threats to this fauna in Peru. We characterize the illegal trade in primates through empirical and ethnographic data. We collected data from traffic routes and centers throughout Peru and evaluate current efforts to combat this traffic. Based on our findings from 2,070 instances of wildlife crime involving 6,872 primates, we estimate the domestic trade in primates for pets and bushmeat in Peru in the hundreds of thousands per year, with the larger bodied Atelidae facing the highest direct consequences. We found that government authorities lack sufficient staff, capacity, resources, infrastructure, and protocols to efficiently combat illegal trade in primates. Also, the complicated legal framework and lack of cooperation and antagonism with the public further limit these efforts. Wildlife authorities in Peru are able to confiscate only a fraction of primates traded and mostly intervene in cases of private pet owners rather than traffickers. We estimate that the current rate of illegal trade in primates is comparable to levels of trade prior to the 1973 ban on primates' exportation. The combination of direct observations on primate trade and ethnographic data allows a comprehensive look at primate trade in Peru. We call upon decision makers and international funders to channel their efforts toward "on the ground" actions such as increasing the ability of the authorities to act, giving them "in action" training in law enforcement and establishing strict control measures against corruption. Am. J. Primatol. 79:e22516, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26684270 TI - Contamination Relative to the Activation Timing of Filtered-Exhaust Helmets. AB - BACKGROUND: Filtered-exhaust helmet systems are commonplace during total joint arthroplasty, but their ability to limit intraoperative contamination has been questioned. We hypothesized that activation of the airflow system after complete gowning would lead to decreased contamination of the surgical environment. METHODS: Using a fluorescent particle model, the maximal particle spread from a filtered-exhaust helmet and contamination of the surgical environment based on timing of airflow activation through simulated surgical gowning procedures were evaluated. RESULTS: Helmet airflow analysis revealed particle spread greater than 5 feet in all trials. Activation before gowning resulted in a significantly greater contamination in the control group compared with the experimental group (P = .014). CONCLUSIONS: We recommend complete surgical gowning before activation of the airflow system. PMID- 26684272 TI - Nontumoral portal vein thrombosis in patients awaiting liver transplantation. AB - Portal vein thrombosis (PVT) occurs in approximately 2%-26% of the patients awaiting liver transplantation (LT) and is no longer an absolute contraindication for LT. Nearly half of PVT cases are accidentally found during the LT procedure. The most important risk factor for PVT development in cirrhosis may be the severity of liver disease and reduced portal blood flow. Whether other inherited or acquired coagulation disorders also play a role is not yet clear. The development of PVT may have no effect on the liver disease progression, especially when it is nonocclusive. PVT may not increase the risk of wait-list mortality, but it is a risk factor for poor early post-LT mortality. Anticoagulation and transjugular intrahepatic portosystemic shunt (TIPS) are 2 major treatment strategies for patients with PVT on the waiting list. The complete recanalization rate after anticoagulation is approximately 40%. The role of TIPS to maintain PV patency for LT as the primary indication has been reported, but the safety and efficacy should be further evaluated. PVT extension and degree may determine the surgical technique to be used during LT. If a "conventional" end-to-end portal anastomotic technique is used, there is not a major impact on post-LT survival. Post-LT PVT can significantly reduce both graft and patient survival after LT and can preclude future options for re-LT. PMID- 26684273 TI - Protein arrays for biomarker discovery in lupus. AB - Lupus is one of the most common autoimmune diseases, yet many mechanisms of its pathogenesis are not fully known. Over the last few years, advances in protein array technology have accelerated rapidly, resulting in many promising insights toward the discovery of novel lupus biomarkers that may become useful in disease diagnosis and management. Still, only two types of analytical protein arrays thus far, being antibody and antigen arrays, have found notable usage toward lupus biomarker discovery. In this review, we summarize current protein array technologies being used for biomarker discoveries in lupus and associated biomarker findings, as well as protein arrays that are likely to be used for lupus biomarker discovery in the near future. PMID- 26684274 TI - The Influence of Serum Uric Acid on Bone Mineral Density, Hip Geometry, and Fracture Risk: The Rotterdam Study. AB - CONTEXT: The role of uric acid (UA) in skeletal metabolism remains to be unraveled. OBJECTIVE: We prospectively investigated the association between UA, bone mineral density at the femoral neck (FN-BMD), hip bone geometry parameters, and incident fracture risk and examined whether the associations were modified by age and vitamin C intake. PARTICIPANTS AND SETTING: Data of 5074 participants of The Rotterdam Study, a prospective population-based cohort. EXPOSURE: Serum UA was assessed at baseline. MAIN OUTCOMES AND MEASURES: FN-BMD was measured at baseline, and at second, third, and fourth visits of the Rotterdam Study. Hip bone geometry parameters were measured at baseline and at the second and third visits. RESULTS: Serum UA levels (per SD increase) were positively associated with FN-BMD (beta = 0.007 g/cm(2); 95% confidence interval [CI] = 0.002-0.01), thicker cortices (beta = 0.002 cm; 95% CI = 0.0003-0.002), lower bone width (beta = -0.013 cm; 95% CI = -0.23 to -0.003), and lower cortical buckling ratio (beta = -0.19; 95% CI = -0.33 to -0.06). The effects of UA on FN-BMD and cortical buckling ratio tended to become stronger over time. Hazard ratios and 95% CIs per SD increase of baseline UA levels for the development of any type of incident fractures, nonvertebral fractures, and osteoporotic fractures were 0.932 (0.86 0.995), 0.924 (0.856-0.998), and 0.905 (0.849-0.982), respectively. These associations were more prominent in older individuals (age, >65 y) and in participants with high intakes of vitamin C (> median). CONCLUSIONS: Higher levels of serum UA are associated with higher BMD (at the expense of thicker cortices and narrower bone diameters) and may be a protective factor in bone metabolism. However, interactions with age and vitamin C may be present. PMID- 26684276 TI - Prediction of Declining Renal Function and Albuminuria in Patients With Type 2 Diabetes by Metabolomics. AB - CONTEXT: Renal disease in type 2 diabetes mellitus (T2DM) is associated with excess morbidity/mortality. Although estimated glomerular filtration rate (eGFR) and albuminuria are routine for assessing renal impairment, novel biomarkers could improve risk stratification and prediction. OBJECTIVE: To identify specific biomarkers of progression of renal dysfunction. DESIGN: Prospective observational. SETTING: Academic diabetes clinics. PATIENTS: A total of 286 T2DM patients (age, 62 +/- 8 y; glycosylated hemoglobin, 7.2 +/- 0.9%; eGFR, 85 +/- 20 mL . min(-1) . 1.73 m(2)). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Progression of eGFR and albuminuria. RESULTS: We performed screening metabolomics in serum and urine samples by gas chromatography/mass spectroscopy (MS) and ultra high performance liquid chromatography/MS/MS. Biomarker identification was performed by random forest using an eGFR cutoff of < 60 mL . min(-1) . 1.73 m(2) or an albumin/creatinine ratio (ACR) cutoff >= 30 mg/g as response variables. At follow-up, eGFR had declined by 16 [9] (median [interquartile ratio]) mL . min( 1) . 1.73 m(2), and ACR had increased by 41 [135] mg/g in patients in the respective top quartile of changes from baseline. Clinical parameters (gender, age, fasting glucose, and baseline eGFR) predicted outcome, with receiver operator characteristics curve (ROC) = 0.671. The five serum metabolites best correlated with either eGFR < 60 or ACR >= 30 at baseline were tested for their ability to improve clinical prediction. The sum of C-glycosyl tryptophan, pseudouridine, and N-acetylthreonine (MetIndex) raised the ROC to 0.739 (P < .0001). eGFR decline was predicted by the top MetIndex quartile (odds ratio = 5.48 [95% confidence interval, 2.23-14.47]). MetIndex also predicted an ACR increase with an odds ratio of 2.82 [1.20-7.03] and a ROC of 0.750. Top urine metabolites did not add significant predictivity. CONCLUSIONS: A limited number of circulating intermediates of amino acid and nucleotide pathways carry clinically significant predictivity for deterioration of renal function in well controlled T2DM. PMID- 26684275 TI - Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity. AB - CONTEXT: Alterations in bile acid (BA) synthesis and transport have the potential to affect multiple metabolic pathways in the pathophysiology of obesity. OBJECTIVE: The objective of the study was to investigate the effects of obesity on serum fluctuations of BAs and markers of BA synthesis. DESIGN: We measured BA fluctuations in 11 nonobese and 32 obese subjects and BA transporter expression in liver specimens from 42 individuals and specimens of duodenum, jejunum, ileum, colon, and pancreas from nine individuals. MAIN OUTCOME MEASURES: We analyzed serum BAs and markers of BA synthesis after overnight fasting, during a hyperinsulinemic-euglycemic clamp, or a mixed-meal tolerance test and the association of BA transporter expression with body mass index. RESULTS: BA synthesis markers were 2-fold higher (P < .01) and preferentially 12alpha hydroxylated (P < .05) in obese subjects, and both measures were correlated with clamp-derived insulin sensitivity (r = -0.62, P < .0001, and r = -0.39, P = .01, respectively). Insulin infusion acutely reduced serum BAs in nonobese subjects, but this effect was blunted in obese subjects (deltaBAs -44.2% vs -4.2%, P < .05). The rise in serum BAs postprandially was also relatively blunted in obese subjects (deltaBAs +402% vs +133%, P < .01). Liver expression of the Na+ taurocholate cotransporting polypeptide and the bile salt export pump were negatively correlated with body mass index (r = -0.37, P = .02, and r = -0.48, P = .001, respectively). CONCLUSIONS: Obesity is associated with increased BA synthesis, preferential 12alpha-hydroxylation, and impaired serum BA fluctuations. The findings reveal new pathophysiological aspects of BA action in obesity that may lend themselves to therapeutic targeting in metabolic disease. PMID- 26684277 TI - A modern approach to ERCP: maintaining efficacy while optimising safety. AB - BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging and complications such as post-ERCP pancreatitis (PEP) remain a concern. Modern ERCP techniques aim to maintain efficacy and improve safety. There are limited data regarding efficacy and safety of ERCP carried out by a newly qualified practitioner using modern techniques. The aim of the present study was to conduct an ERCP practice audit and compare it with an Australian national survey in order to review the evidence base underlying modern ERCP practice. METHODS: All ERCP carried out by a newly qualified practitioner, using prospectively collected data, from September 2011 to May 2015, were audited. Outcomes were compared to an Australia-wide survey of ERCP practice. A literature review was carried out regarding recent developments in ERCP practice. RESULTS: Audit results correlated well with national data. All 478 ERCP were therapeutic and had pre-procedure imaging. Wire-guided biliary cannulation was used. Success rate was 97%. Overall adverse-event rate was 0.8%. Choledocholithiasis was the predominant indication (72%). Biliary cannulation was successful in 338 of 348 naiive papillae. Of these, there were 53 (16%) difficult cannulations but the needle-knife sphincterotomy (NKS) rate was low compared to national data (13% vs 33%). Rate of dual-wire cannulation technique was higher (87% vs 30%). Pancreatic duct stenting (done in 32 cases [70% of dual-wire cannulation cases]) and rectal indomethacin (25%) were used to reduce PEP risk. CONCLUSIONS: A newly qualified ERCP proceduralist achieved high success rates with minimal adverse events using modern techniques. Practice was consistent with national data, although dual-wire cannulation technique was preferred to NKS. Evidence base for modern ERCP techniques was reviewed. ERCP efficacy and safety should be monitored by practice audit. PMID- 26684278 TI - Cancer Patients' Experiences of Using Mistletoe (Viscum album): A Qualitative Systematic Review and Synthesis. AB - OBJECTIVE: Systematic reviews of mistletoe therapy (MT) trials in cancer show promising results in improvement of patients' quality of life during chemotherapy and reduction of fatigue. However, patients' experiences of side effects and the acceptability, tolerability, and perceived benefits of MT have not been systematically reviewed. The aim of this study was to systematically review and synthesise the results of qualitative studies of cancer patients' experiences of using MT. DESIGN: A systematic search was conducted in MEDLINE, Embase, PsychLIT, CINAHL, and AMED to identify qualitative studies of MT. Articles were screened independently by two reviewers and critically appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of the findings was carried out. RESULTS: One hundred and seventy-three papers were identified; 156 were excluded at initial screening. Seventeen papers were read in full, 14 of which were excluded. Three articles about patients' experiences of MT alongside conventional treatment were included in the synthesis, either as a monotherapy (two articles) or as part of a package of anthroposophic treatment (one article). Patients reported demonstrable changes to their physical, emotional, and psychosocial well-being following MT, as well as a reduction in chemotherapy side effects. Self-reported side effects from MT were few, and the studies suggest good adherence to the therapy. Self-injection gave patients a sense of empowerment through involvement in their own treatment. CONCLUSIONS: A systematic search revealed a small number of qualitative studies of MT in cancer. These were effectively combined to provide a detailed overview of patients' experiences in order to complement the developing evidence base from trials. Given the variation in context of MT delivery across the articles, it is not possible to ascribe changes in patients' quality of life specifically to MT. The results of this review will help in the design of outcome measures that more fully capture patients' experiences. It is essential to embed qualitative research of patients' experiences of MT and other CAM therapies within future trials. PMID- 26684279 TI - The evolution of T-cell depletion in haploidentical stem-cell transplantation. AB - T-cell depletion (TCD) can prevent the onset of graft-versus-host disease (GvHD) in animal models of bone marrow transplantation; this manipulation enabled the successful application in the 1980s of T-cell depleted bone marrow (BM) for the treatment of babies with severe combined immune deficiency (SCID). However, in leukaemia patients, implementation of T-cell depletion has been more difficult, especially due to high rate of graft-rejection, leukaemia relapse and delayed immune reconstitution. These hurdles were gradually overcome by modifying the cell composition of the graft, and by reducing the toxicities associated with conditioning protocols. Although no 'gold standard' TCD method exists, T-cell depletion in its modern forms could offer clinical benefit, even for patients with a matched sibling donor. PMID- 26684280 TI - Polarized Couples in Therapy: Recognizing Indifference as the Opposite of Love. AB - How can a couple "fall in love" and then subsequently "stumble out of love"? For centuries, this question has perplexed partners, researchers, and therapists alike. Unlike falling out of love, which may be a long-term gradual decline in love, falling in love may occur without much deliberation like the famous "love at first sight." During a developing love relationship, couples are more susceptible to ignoring a myriad of factors that will eventually influence their relationship. These ignored personal and general factors become increasingly conspicuous after the relationship is established. When facing relationship difficulties, the presence or absence of mutual love and intimacy steers the couple's relationship toward continuity or termination. Emotional indifference (which is the opposite of love) diminishes love and care; the terms marital disaffection and romantic disengagement are used synonymously to represent emotional indifference in couples. Marital disaffection is one of the central concerns of couples entering therapy. Nevertheless, spouses may enter therapy with divergent goals that may be polar opposites. Therefore, treatment of polarized or different agenda couples is challenging because disaffected spouses may be seeking counseling to break the bond at a safe venue, while their partners may still be obliviously hoping for the rebirth of their lost love. This article reviews marital disaffection/romantic disengagement and discusses counseling options for polarized couples. PMID- 26684282 TI - Editorial 2016. PMID- 26684281 TI - Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease. AB - BACKGROUND: Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect. This is an update of a previously published version of this review. OBJECTIVES: To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 28 September 2015. SELECTION CRITERIA: Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors. MAIN RESULTS: Two studies comprising 287 participants were included. One study (with an overall unclear to high risk of bias) involved 253 participants and the quality of the evidence for most outcomes was very low. This study, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group. The second study (unclear risk of bias) including 34 participants and was a conference abstract with limited data and only addressed one of the predefined outcomes of the review; i.e. pain intensity. After one day pain intensity reduced more, as reported on a visual analogue scale, in the dalteparin group than in the placebo group, mean difference -1.30 (95% confidence interval 1.60 to -1.00), with the quality of evidence rated very low. The most important reasons for downgrading the quality of evidence were serious risk of bias and imprecision (due to low sample size or low occurrence of events). AUTHORS' CONCLUSIONS: Based on the results of two studies, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study. PMID- 26684283 TI - Highlights from the 31st ECTRIMS congress - Barcelona 2015. PMID- 26684285 TI - Being constipated: A bad omen for your cardiovascular system? PMID- 26684286 TI - Nahuoic Acids B-E, Polyhydroxy Polyketides from the Marine-Derived Streptomyces sp. SCSGAA 0027. AB - Four new polyol polyketides containing a decalin ring, nahuoic acids B-E (1-4), together with a known analogue, nahuoic acid A (5), possessing an unprecedented carbon skeleton, were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their structures were determined by detailed analysis of spectroscopic data and chemical transformations including acetonide formation and Mosher's ester method. Compounds 1-5 showed weak antibiofilm activity against Shewanella onedensis MR-1 biofilm. This is the first series of analogues of the novel selective SETD8 inhibitor nahuoic acid A. PMID- 26684287 TI - Influence of the Outer Ligands on Metal-to-Ligand Charge Transfer in Solvated Manganese Porphyrins. AB - Two manganese porphyrin complexes, manganese tetraphenylporphyrin chloride (MnTPP Cl) and manganese octaethylporphyrin chloride (MnOEP-Cl), exhibit distinctive spectral features of metal-to-ligand charge-transfer (MLCT) when dissolved in dichloromethane, characterized by resonant inelastic X-ray scattering at the Mn L edge and N K-edge. The metal-ligand orbital mixing that mediates the MLCT is analyzed with the help of density functional theory/restricted open-shell configuration interaction singles calculations. On the basis of experimental and theoretical analyses, the distinctive MLCT is argued to originate from alteration of the porphyrin outer ligands: phenyl groups in MnTPP-Cl and ethyl groups in MnOEP-Cl. PMID- 26684288 TI - Diagnostic parameters of serological ELISA for invasive amoebiasis, using antigens preserved without enzymatic inhibitors. AB - Amoebiasis is the third cause of death due to parasites in the world. Although, numerous serodiagnostic and salivary tests have been developed, the majority of these assays lack sensitivity in endemic zones to detect acute amoebic liver abscess. The two main limiting factors to develop reliable assays are the high levels of anti-amoeba antibodies in populations living in endemic zones, and the proteolysis of amoebic extracts even treated with inhibitors. Our group reported a method to preserve amoebic antigens without using enzymatic inhibitors (IC:MC fraction) that shows stability for years. Here we describe the development of a serologic ELISA to diagnose amoebiasis made with IC: MC antigens, and its validation for clinical use in endemic areas. In our study, we included sera from 66 patients diagnosed with acute amoebic liver abscess and 33 volunteers living in an endemic area for amoebiasis. Our assay was compared with an indirect haemagglutination assay (IHA) an ELISA elaborated with antigens derived from untreated trophozoites. The ELISA made with IC: MC antigens presented more reproducibility compared to other assays. Sera from 95% ALA patients showed a positive value. The ELISA (IC: MC) detected 97% of patients with ALA compared to an 81% using IHA. The parameters of ELISA (vs. IHA) were Sensitivity 98% (81%), Specificity 96% (97%), Positive predictive value 98% (96%), Negative predictive value 96% (73%) and Accuracy 98% (87%). A negative serologic test does not rule out the diagnosis of invasive amoebiasis. The ELISA made with antigens preserved without using enzymatic inhibitors has valuable serodiagnostic value to diagnose acute amoebic liver abscess, even in populations living in endemic zones of amoebiasis carrying antibodies against amoebas. In conclusion, ELISA-IC:MC presented better diagnostic parameters than IHA although a negative serologic test does not rule out acute invasive amoebiasis. PMID- 26684289 TI - Potential roles of disordered airway microbiota in patients with severe asthma. PMID- 26684290 TI - IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa. AB - BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown. OBJECTIVE: We sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP. METHODS: Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Control nasal biopsy specimens and blood were obtained from healthy volunteers. Tissue was cultured in a short-term explant model. T-cell surface phenotype/intracellular cytokines were assessed by means of flow cytometry. T cell receptor variable beta-chain analysis was performed with the immunoSEQ assay. Microarrays were performed for gene expression analysis. RESULTS: IL-25 receptor (IL-17RB)-expressing TH2 effector cells were identified in nasal polyp tissue but not the healthy nasal mucosa or periphery. IL-17RB(+)CD4(+) polyp derived TH2 cells coexpressed ST2 (IL-33 receptor) and responded to IL-25 and IL 33 with enhanced IL-5 and IL-13 production. Within IL-17RB(+)CD4(+) T cells, several identical T-cell receptor variable beta-chain complementarity-determining region 3 sequences were identified in different subjects, suggesting clonal expansion driven by a common antigen. Abundant IL-17-producing T cells were observed in both healthy nasal mucosal and polyp populations, with TH17-related genes the most overexpressed compared with peripheral blood T cells. CONCLUSION: IL-25 and IL-33 can interact locally with IL-17RB(+)ST2(+) polyp T cells to augment TH2 responses in patients with CRSwNP. A local TH17 response might be important in healthy nasal mucosal immune homeostasis. PMID- 26684292 TI - Reply. PMID- 26684291 TI - IgE epitope proximity determines immune complex shape and effector cell activation capacity. AB - BACKGROUND: IgE-allergen complexes induce mast cell and basophil activation and thus immediate allergic inflammation. They are also important for IgE-facilitated allergen presentation to T cells by antigen-presenting cells. OBJECTIVE: To investigate whether the proximity of IgE binding sites on an allergen affects immune complex shape and subsequent effector cell activation in vitro and in vivo. METHODS: We constructed artificial allergens by grafting IgE epitopes in different numbers and proximity onto a scaffold protein. The shape of immune complexes formed between artificial allergens and the corresponding IgE was studied by negative-stain electron microscopy. Allergenic activity was determined using basophil activation assays. Mice were primed with IgE, followed by injection of artificial allergens to evaluate their in vivo allergenic activity. Severity of systemic anaphylaxis was measured by changes in body temperature. RESULTS: We could demonstrate simultaneous binding of 4 IgE antibodies in close vicinity to each other. The proximity of IgE binding sites on allergens influenced the shape of the resulting immune complexes and the magnitude of effector cell activation and in vivo inflammation. CONCLUSIONS: Our results demonstrate that the proximity of IgE epitopes on an allergen affects its allergenic activity. We thus identified a novel mechanism by which IgE-allergen complexes regulate allergic inflammation. This mechanism should be important for allergy and other immune complex-mediated diseases. PMID- 26684293 TI - Fcgamma-receptor 3B (FCGR3B) copy number variations in patients with eosinophilic granulomatosis with polyangiitis. PMID- 26684295 TI - Limited thymic recovery after extracorporeal photopheresis in a low-body-weight patient with acute graft-versus-host disease of the skin. PMID- 26684297 TI - A Molecular Chaperone for G4-Quartet Hydrogels. AB - Thioflavin T (ThT) functions as a molecular chaperone for gelation of water by guanosine and lithium borate. Substoichiometric ThT (1 mol % relative to hydrogelator) results in faster hydrogelation as monitored by (1)H NMR and visual comparison. Vial-inversion tests and rheology show that ThT increases the stiffness of the Li(+) guanosine-borate (GB) hydrogel. In addition, the dye promotes relatively rapid and complete repair of a Li(+) GB hydrogel destroyed by shearing. We used rheology to show that other planar aromatics, some cationic and one neutral dye (methylene violet), also stiffened the Li(+) GB hydrogel. Data from powder X-ray diffraction, UV, and circular dichroism spectroscopy and ThT fluorescence indicate that G4 quartets are formed by the Li(+) GB system. We observed a species in solution by (1)H NMR that was intermediate in size between monomeric gelator and NMR-invisible hydrogel. The concentration of this intermediate decreased much faster when ThT was present in solution, again showing that the dye can accelerate hydrogel formation. We propose that ThT functions as a molecular chaperone by end stacking on terminal G4-quartets and promoting the assembly of these smaller fragments into longer G4-based structures that can then provide more cross-linking sites needed for hydrogelation. PMID- 26684294 TI - Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution. AB - BACKGROUND: Asthma is a complex disorder influenced by genetics and the environment. Recent findings have linked abnormal DNA methylation in T cells with asthma; however, the potential dysregulation of methylation in airway epithelial cells is unknown. Studies of mouse models of asthma have observed greater levels of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation 1 (TET1) expression in lungs. TET proteins are known to catalyze methylation through modification of 5-methylcytosine to 5-hmC. OBJECTIVE: We sought to examine the association of TET1 methylation with asthma and traffic-related air pollution (TRAP). METHODS: TET1 methylation levels from DNA derived from nasal airway epithelial cells collected from 12 African American children with physician diagnosed asthma and their nonasthmatic siblings were measured by using Illumina 450K arrays. Regions of interest were verified by means of locus-specific pyrosequencing in 35 sibling pairs and replicated in an independent population (n = 186). Exposure to TRAP in participants' early life and at current home addresses was estimated by using a land-use regression model. Methylation studies in saliva, PBMCs, and human bronchial epithelial cells were done to support our findings. RESULTS: Loss of methylation at a single CpG site in the TET1 promoter (cg23602092) and increased global 5-hmC levels were significantly associated with asthma. In contrast, TRAP exposure at participants' current homes significantly increased methylation at the same site. Patterns were consistent across tissue sample types. 5-Aza-2'-deoxycytidine and diesel exhaust particle exposure in human bronchial epithelial cells was associated with altered TET1 methylation and expression and global 5-hmC levels. CONCLUSIONS: Our findings suggest a possible role of TET1 methylation in asthmatic patients and response to TRAP. PMID- 26684296 TI - [Traumatic brain injury in anticoagulated patients : Hemostatic therapy for the treatment of intracranial hemorrhage]. AB - Impaired hemostasis represents a major risk factor for increased morbidity and mortality in patients with traumatic intracranial hemorrhage. In cases of polytrauma with major bleeding, hyperfibrinolysis may develop and this may result in excessive coagulopathy. Patients receiving antithrombotic medication and suffering from intracranial hemorrhage are at particular risk for the development of neurological sequelae due to the increased tendency to bleeding. This article outlines the principles of hemostatic therapy of traumatic intracranial hemorrhage during antithrombotic treatment. The basic principles of the pathophysiology and effects of coagulation impairment in this patient population are reviewed. Furthermore, the use of specific coagulation tests and the administration of hemostatic substances are discussed. PMID- 26684298 TI - Time Preferences Predict Mortality among HIV-Infected Adults Receiving Antiretroviral Therapy in Kenya. AB - BACKGROUND: Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. METHODS: HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence >=90%. RESULTS: Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence >=90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). CONCLUSION: High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding. PMID- 26684299 TI - Discovering Hominins - Application of Medical Computed Tomography (CT) to Fossil Bearing Rocks from the Site of Malapa, South Africa. AB - In the South African context, computed tomography (CT) has been used applied to individually prepared fossils and small rocks containing fossils, but has not been utilized on large breccia blocks as a means of discovering fossils, and particularly fossil hominins. Previous attempts at CT imaging of rocks from other South African sites for this purpose yielded disappointing results. For this study, 109 fossil- bearing rocks from the site of Malapa, South Africa were scanned with medical CT prior to manual preparation. The resultant images were assessed for accuracy of fossil identification and characterization against the standard of manual preparation. The accurate identification of fossils, including those of early hominins, that were not visible on the surface of individual blocks, is shown to be possible. The discovery of unexpected fossils is reduced, thus lowering the potential that fossils could be damaged through accidental encounter during routine preparation, or even entirely missed. This study should significantly change the way fossil discovery, recovery and preparation is done in the South African context and has potential for application in other palaeontological situations. Medical CT imaging is shown to be reliable, readily available, cost effective and accurate in finding fossils within matrix conglomerates. Improvements in CT equipment and in CT image quality are such that medical CT is now a viable imaging modality for this palaeontological application. PMID- 26684300 TI - The effects of starvation on fast-start escape and constant acceleration swimming performance in rose bitterling (Rhodeus ocellatus) at two acclimation temperatures. AB - To investigate the effects of starvation and acclimation temperature on the escape ability of juvenile rose bitterling (Rhodeus ocellatus), we measured the fast-start escape and constant acceleration swimming performance of fish fasted for 0 (control), 1 and 2 weeks and half-lethal periods (6 or 4 weeks) at two temperatures (15 and 25 degrees C). Fish acclimated at a high temperature exhibited shorter response latency (R), higher maximum linear velocity (V max) and longer escape distance during escape movement (D 120ms) than those at the low temperature. Starvation resulted in a significant decrease in V max and D 120ms at either low or high temperature and a significant increase in R at only the high temperature in the half-lethal period groups (P < 0.05). The relationship between V max (Y, m s(-1)) and starvation time (X, week) was Y 15 = -0.062X + 1.568 (r = -0.665, n = 36, P < 0.001) at low temperature and Y 25 = -0.091X + 1.755 (r = -0.391, n = 40, P = 0.013) at high temperature. The relationship between U cat (Y, cm s(-1)) and starvation time (X, week) was Y 15 = -1.649X + 55.418 (r = -0.398, n = 34, P = 0.020) at low temperature and Y 25 = -4.917X + 62.916 (r = -0.793, n = 33, P < 0.001) at high temperature. The slopes of equations showed a significant difference between low and high temperature (F 1,63 = 9.688, P = 0.003), which may be due to the different energy substrate utilization when faced with food deprivation at different temperatures. PMID- 26684301 TI - Molecular Properties and Functional Divergence of the Dehydroascorbate Reductase Gene Family in Lower and Higher Plants. AB - Dehydroascorbate reductase (DHAR), which reduces oxidized ascorbate, is important for maintaining an appropriate ascorbate redox state in plant cells. To date, genome-wide molecular characterization of DHARs has only been conducted in bryophytes (Physcomitrella patens) and eudicots (e.g. Arabidopsis thaliana). In this study, to gain a general understanding of the molecular properties and functional divergence of the DHARs in land plants, we further conducted a comprehensive analysis of DHARs from the lycophyte Selaginella moellendorffii, gymnosperm Picea abies and monocot Zea mays. DHARs were present as a small gene family in all of the land plants we examined, with gene numbers ranging from two to four. All the plants contained cytosolic and chloroplastic DHARs, indicating dehydroascorbate (DHA) can be directly reduced in the cytoplasm and chloroplast by DHARs in all the plants. A novel vacuolar DHAR was found in Z. mays, indicating DHA may also be reduced in the vacuole by DHARs in Z. mays. The DHARs within each species showed extensive functional divergence in their gene structures, subcellular localizations, and enzymatic characteristics. This study provides new insights into the molecular characteristics and functional divergence of DHARs in land plants. PMID- 26684302 TI - Short term global health experiences and local partnership models: a framework. AB - Contemporary interest in in short-term experiences in global health (STEGH) has led to important questions of ethics, responsibility, and potential harms to receiving communities. In addressing these issues, the role of local engagement through partnerships between external STEGH facilitating organization(s) and internal community organization(s) has been identified as crucial to mitigating potential pitfalls. This perspective piece offers a framework to categorize different models of local engagement in STEGH based on professional experiences and a review of the existing literature. This framework will encourage STEGH stakeholders to consider partnership models in the development and evaluation of new or existing programs.The proposed framework examines the community context in which STEGH may occur, and considers three broad categories: number of visiting external groups conducting STEGH (single/multiple), number of host entities that interact with the STEGH (none/single/multiple), and frequency of STEGH (continuous/intermittent). These factors culminate in a specific model that provides a description of opportunities and challenges presented by each model. Considering different models, single visiting partners, working without a local partner on an intermittent (or even one-time) basis provided the greatest flexibility to the STEGH participants, but represented the least integration locally and subsequently the greatest potential harm for the receiving community. Other models, such as multiple visiting teams continuously working with a single local partner, provided an opportunity for centralization of efforts and local input, but required investment in consensus-building and streamlining of processes across different groups. We conclude that involving host partners in the design, implementation, and evaluation of STEGH requires more effort on the part of visiting STEGH groups and facilitators, but has the greatest potential benefit for meaningful, locally-relevant improvements from STEGH for the receiving community. There are four key themes that underpin the application of the framework: 1. Meaningful impact to host communities requires some form of local engagement and measurement. 2. Single STEGH without local partner engagement is rarely ethically justified. 3. Models should be tailored to the health and resource context in which the STEGH occurs. 4. Sending institutions should employ a model that ultimately benefits local receiving communities first and STEGH participants second. Accounting for these themes in program planning for STEGH will lead to more equitable outcomes for both receiving communities and their sending partners. PMID- 26684304 TI - Crescentic glomerulonephritis in children: a single centre experience. AB - BACKGROUND: Crescentic glomerulonephritis (CsGN) is characterized by crescents in 50% or more of glomeruli and clinically by a sudden and progressive decline in renal function. METHODS: We evaluated the etiology, clinical features, prognostic factors and long-term outcome of CsGN. Between January 2000 and December 2010, 45 children (26 girls, 19 boys) with biopsy-proven CsGN (>50% crescents) were investigated retrospectively. RESULTS: The mean age of the patients was 130.86+/ 33.77 months. The mean duration of symptoms prior to diagnosis was 26+/-12 days (4-40 days). Most of the children had hypertension (62.2%), macroscopic hematuria (73.3%), oligoanuria (44.4%), edema (51.1%) and purpuric rash (40%) at presentation. The final clinical status of the patients was complete remission (n=21), partial remission (n=5) or chronic kidney disease (n=19). Adverse outcomes were significantly associated with a long duration between the onset of symptoms and treatment (P=0.038), the presence of oligoanuria (P=0.006), a severe decreased glomerular filtration rate (GFR <30 mL/min/1.73m2) and the need for dialysis (P=0.003) on admission, the ratio of crescents (>75%) (P=0.03), and the ratio of fibrous crescents (P=0.015). CONCLUSION: The outcome of CsGN in children continues to be poor, and it should be treated as a renal emergency. PMID- 26684305 TI - Outcome in neonates with necrotizing enterocolitis and patent ductus arteriosus. AB - BACKGROUND: There is no agreement of the influence of patent ductus arteriosus (PDA) on outcomes in patients with necrotizing enterocolitis (NEC). In this study, we assessed the influence of PDA on NEC outcomes. METHODS: A retrospective study of 131 infants with established NEC was performed. Outcomes (death, disease severity, need for surgery, hospitalization duration), as well as multiple clinical parameters were compared between NEC patients with no congenital heart disease (n=102) and those with isolated PDA (n=29). Univariate, multivariate and stepwise logistic regression analyses were performed. RESULTS: Birth weight and gestational age were significantly lower in patients with PDA [median (95% CI): 1120 g (1009-1562 g), 28.4 wk (27.8-30.5 wk)] than in those without PDA [median (95% CI): 1580 g (1593-1905 g), 32.4 wk (31.8-33.5 wk); P<0.05]. The risk of NEC attributable fatality was higher in NEC patients with PDA (35%) than in NEC patients without PDA (14%)[univariate odds ratio (OR)=3.3, 95% CI: 1.8-8.6, P<0.05; multivariate OR=2.4, 95% CI: 0.82-2.39, P=0.111]. Significant independent predictors for non-survival within the entire cohort were advanced disease severity stage III (OR=27.9, 95% CI: 7.4-105, P<0.001) and birth weight below 1100 g (OR=5.7, 95% CI: 1.7-19.4, P<0.01). CONCLUSIONS: In patients with NEC, the presence of PDA is associated with an increased risk of death. However, when important differences between the two study groups are controlled, only birth weight and disease severity may independently predict mortality. PMID- 26684303 TI - A Trichomonas vaginalis Rhomboid Protease and Its Substrate Modulate Parasite Attachment and Cytolysis of Host Cells. AB - Trichomonas vaginalis is an extracellular eukaryotic parasite that causes the most common, non-viral sexually transmitted infection worldwide. Although disease burden is high, molecular mechanisms underlying T. vaginalis pathogenesis are poorly understood. Here, we identify a family of putative T. vaginalis rhomboid proteases and demonstrate catalytic activity for two, TvROM1 and TvROM3, using a heterologous cell cleavage assay. The two T. vaginalis intramembrane serine proteases display different subcellular localization and substrate specificities. TvROM1 is a cell surface membrane protein and cleaves atypical model rhomboid protease substrates, whereas TvROM3 appears to localize to the Golgi apparatus and recognizes a typical model substrate. To identify TvROM substrates, we interrogated the T. vaginalis surface proteome using both quantitative proteomic and bioinformatic approaches. Of the nine candidates identified, TVAG_166850 and TVAG_280090 were shown to be cleaved by TvROM1. Comparison of amino acid residues surrounding the predicted cleavage sites of TvROM1 substrates revealed a preference for small amino acids in the predicted transmembrane domain. Over expression of TvROM1 increased attachment to and cytolysis of host ectocervical cells. Similarly, mutations that block the cleavage of a TvROM1 substrate lead to its accumulation on the cell surface and increased parasite adherence to host cells. Together, these data indicate a role for TvROM1 and its substrate(s) in modulating attachment to and lysis of host cells, which are key processes in T. vaginalis pathogenesis. PMID- 26684306 TI - Focal seizure associated with human parvovirus B19 infection in a non encephalopathic child. AB - BACKGROUND: The incidence of acute symptomatic (at the time of documented brain insult) seizures and single unprovoked seizures are 29-39 and 23-61 per 100 000 per year, respectively. After stabilization of the patient, finding the etiology of the seizure is of paramount importance. A careful history and physical examination may allow a diagnosis without need for further evaluation. METHODS: In the literature, severe central nervous system involvement has been reported from human parvovirus B19 infection. We reported a previously healthy 7-year-old girl who presented after an episode of focal seizure. She was afebrile and didn't have any focal neurological abnormalities. She had erythematous malar rash along with reticulating pattern of rash over her both upper extremities. RESULTS: Parvovirus infection was suspected due to the characteristic erythematous malar rash. Serum human parvovirus B19 DNA polymerase chain reaction was positive which was consistent with acute parvovirus infection. Further confirmation of current infection was done with Sandwich enzyme immunoassays showing positive anti-B19 IgM Index (>1.1). IgG index was equivocal (0.9-1.1). CONCLUSIONS: We report an extremely rare presentation of non-febrile seizure from acute parvovirus infection in a child without encephalopathy who had an excellent recovery. Timely diagnosis can provide counselling regarding future seizure recurrence risk, curtail expenditure from expensive diagnostic work up and provide additional recommendations about potential risks to a pregnant caregiver. PMID- 26684307 TI - Use of off-label nephrology-related drugs in hospitalized pediatric patients: a retrospective study. AB - BACKGROUND: The information about the use of off-label drugs in pediatric nephrology is still lacking, which leads to increased adverse reactions and medical disputes. We retrospectively analyzed the use of off-label drugs in the in-patient ward of the nephrology department of Nanjing Children's Hospital, China in order to provide more complete information about the use of drugs for children. METHODS: Proportional stratified random sampling was applied to select patients with renal diseases aged 1 month to 18 years, who were admitted to the hospital from October 1, 2012 to September 30, 2013. All nephrology-related drugs prescribed in the hospitalization period and take-home drugs prescribed on discharge were recorded and evaluated as off-label drugs or not from three different perspectives: person-time, prescription, and drug category. RESULTS: From 385 person-times of patients with 1424 prescriptions, according to the ratio between off-label drugs and person-times, drug prescriptions, and drug products, the rates of off-label drugs were 40.78%, 16.64%, and 31.43%, respectively. Low molecular-weight heparin, alfacalcidol and diltiazem were the most commonly used off-label drugs. Infants and younger children were the high-risk population of off-label drug use. The high rate off-label nephrology-related drug use in children was mainly related to lacking clinical research into drugs in children and the pace of drug label's revision, which cannot follow the development of medical science. CONCLUSION: Approximaely half of pediatric patients with renal diseases are usually prescribed with off-label nephrology-related drugs. Analyzing the off-label conditions from different perspectives may lead to various results. More clinical research into drugs for infants and younger children is needed so as to update drug descriptions. PMID- 26684308 TI - Thyroid dysfunction and developmental anomalies in first degree relatives of children with thyroid dysgenesis. AB - BACKGROUND: Familial clustering in patients with permanent congenital hypothyroidism (CH) caused by thyroid dysgenesis (TD) has been reported in developed countries. There is no information on familial TD from developing countries. METHODS: A total of 312 first degree relatives belonging to 80 families of children with TD (group 1) and 40 families of age-matched normal children (group 2) were screened by thyroid ultrasonography, serum total thyroxine (T4) and thyroid stimulating hormone (TSH). RESULTS: Thyroid scintigraphy revealed agenesis in 78.7% of the patients, ectopic gland in 15%, and hypoplasia in 6.2%. The mean thyroid volumes were similar in parents and siblings of both groups. Eight (10.6%) mothers in group 1 were identified to have thyroid hypoplasia as compared with none in group 2 (P=0.03). Serum TSH was significantly higher in group 1 than in group 2 (P=0.004). Sixteen (7.8%) subjects (6 mothers, 5 fathers, and 5 siblings) in group 1 were found to have subclinical hypothyroidism as compared to none in group 2 (P<0.05). Four families were identified to have thyroid developmental anomalies and abnormal thyroid functions accounting for 5% of cases of familial TD in our cohort. CONCLUSION: Thyroid developmental anomalies and thyroid function abnormalities are more frequent in first degree relatives of children with TD as compared with a control population. These findings suggest that possibly there is a genetic component of TD in Indian patients. PMID- 26684309 TI - Tacrolimus for children with refractory nephrotic syndrome: a one-year prospective, multicenter, and open-label study of Tacrobell(r), a generic formula. AB - BACKGROUND: Cyclosporine A and tacrolimus (TAC) are often used as a second-line treatment for children with refractory nephrotic syndrome (NS). This study was undertaken to investigate the efficacy and safety of Tacrobell(r), a locally produced generic form of TAC. METHODS: This study was a one-year prospective, open-label, single-arm, multicenter trial. Fourty-four children with steroid dependent NS (SDNS) and 33 children with steroid-resistant NS (SRNS) were enrolled. The primary endpoints were defined as the remission rates, whereas the secondary endpoints were recognized as the duration of remission and adverse effects of TAC. RESULTS: After one-year treatment, 34 (77.3%) of the 44 patients with SDNS were in complete remission, and 6 (13.6%) were in partial remission. Nineteen (43.2%) patients did not relapse during the study; for those who did relapse, the mean duration of remission was 4.6+/-2.9 months. The number of relapse episodes during the study period (0.90 per patient-year) was significantly lower than that in the preceding year (2.8 per patient-year). After treatment for 3 and 6 months, 12 (36.4%) of the 33 patients with SRNS were in remission, and after treatment for 12 months, the number of patients had increased to 13 (39.4%). The mean time to achieve remission was 4.0+/-3.2 months. After remission (duration, 3.7+/-2.7 months), 12 (54.5%) of 22 patients relapsed. The fasting blood glucose and blood pressure levels during the therapy were similar to those at the time of study entry. CONCLUSIONS: Treatment with Tacrobell(r) was effective and safe for children with refractory NS. The efficacy of this generic form of TAC was better than that of the original TAC formula. PMID- 26684310 TI - Evaluation of carotid intima-media thickness and carotid arterial stiffness in children with adenotonsillar hypertrophy. AB - BACKGROUND: Adenotonsillar hypertrophy can produce cardiopulmonary disease in children. However, it is unclear whether adenotonsillar hypertrophy causes atherosclerosis. This study evaluated carotid intimamedia thickness and carotid arterial stiffness in children with adenotonsillar hypertrophy. METHODS: The study included 40 children with adenotonsillar hypertrophy (age: 5-10 years) and 36 healthy children with similar age and body mass index. Systolic blood pressure, diastolic blood pressure, and pulse pressure were measured in all subjects. Carotid intima-media thickness, carotid arterial systolic diameter, and carotid arterial diastolic diameter were measured using a high-resolution ultrasound device. Based on these measurements, carotid arterial strain, carotid artery distensibility, beta stiffness index, and elasticity modulus were calculated. RESULTS: Carotid intima-media thickness was greater in children with adenotonsillar hypertrophy (0.36+/-0.05 mm vs. 0.34+/-0.04 mm, P=0.02) compared to healthy controls. Beta stiffness index (3.01+/-1.22 vs. 2.98+/-0.98, P=0.85), elasticity modulus (231.39+/-99.23 vs. 226.46+/-83.20, P=0.88), carotid arterial strain (0.17+/-0.06 vs. 0.17+/-0.04, P=0.95), and carotid artery distensibility (13.14+/-3.88 vs. 12.92+/-3.84, P=0.75) were similar between children with adenotonsillar hypertrophy and the healthy controls. CONCLUSIONS: The present study revealed increased carotid intima-media thickness in children with adenotonsillar hypertrophy. The risk of subclinical atherosclerosis may be higher in children with adenotonsillar hypertrophy. PMID- 26684311 TI - Pediatric-specific reference intervals in a nationally representative sample of Iranian children and adolescents: the CASPIAN-III study. AB - BACKGROUND: This study aimed to determine for the first time the age- and gender specific reference intervals for biomarkers of bone, metabolism, nutrition, and obesity in a nationally representative sample of the Iranian children and adolescents. METHODS: We assessed the data of blood samples obtained from healthy Iranian children and adolescents, aged 7 to 19 years. The reference intervals of glucose, lipid profile, liver enzymes, zinc, copper, chromium, magnesium, and 25 hydroxy vitamin D [25(OH)D] were determined according to the Clinical & Laboratory Standards Institute C28-A3 guidelines. The reference intervals were partitioned using the Harris-Boyd method according to age and gender. RESULTS: The study population consisted of 4800 school students (50% boys, mean age of 13.8 years). Twelve chemistry analyses were partitioned by age and gender, displaying the range of results between the 2.5th to 97.5th percentiles. Significant differences existed only between boys and girls at 18 to 19 years of age for low density lipoprotein-cholesterol. 25(OH)D had the only reference interval that was similar to all age groups and both sexes. CONCLUSIONS: This study presented the first national database of reference intervals for a number of biochemical markers in Iranian children and adolescents. It is the first report of its kind from the Middle East and North Africa. The findings underscore the importance of providing reference intervals in different ethnicities and in various regions. PMID- 26684312 TI - Predictive scores for mortality in full-term infants with necrotizing enterocolitis: experience of a tertiary hospital in Southwest China. AB - BACKGROUND: Although many risk factors for mortality of necrotizing enterocolitis (NEC) were investigated, most of them were obtained from preterm infants, and few works focused on the prognostic risk factors in fullterm infants. This study aimed to identify risk factors and develop a prediction score model for mortality in fullterm neonates with NEC. METHODS: The risk factors were analyzed retrospectively by bivariate and multivariate logistic regression analysis in 153 full-term neonates with NEC, who were hospitalized in Children's Hospital of Chongqing Medical University from 2000 to 2013. A prediction score model was developed according to the regression coefficients of risk factors. RESULTS: The mortality of the infants was 19.6% (30/153). The non-survivors had a younger age of diagnosis and advanced stage of NEC (P<0.05). They had a higher prevalence of respiratory failure, intestinal perforation, peritonitis and other complications, compared with the survivors (P<0.05). On the day of diagnosis, the nonsurvivors were more likely to have abnormal laboratory indicators than survivors (P<0.05). Age at diagnosis [odds ratio (OR)=0.91, 95% confidence interval (CI)=0.836-0.99], respiratory failure (OR=2.76, 95% CI=1.10-6.92), and peritonitis (OR=26.36, 95% CI=7.52-173.92) had significant independent contributions to death. A score model predicting death was developed, and the area under the receiver operating characteristic curve was 0.869 (95% CI=0.803-0.935). All infants with scores >=8 died. CONCLUSION: Younger age at diagnosis, peritonitis, and respiratory failure might be risk factors for the mortality of full-term infants with NEC. Infants with a predictive score of 8 were at high risk for death. PMID- 26684313 TI - Comparison of different noninvasive diagnostic methods for biliary atresia: a meta-analysis. AB - BACKGROUND: This study was undertaken to retrospectively analyze the accuracy of different methods in differentiating biliary atresia from neonatal jaundice. METHODS: A search was made in MEDLINE, and the Web of Science for relevant original articles published in English; methodological quality of the included studies was also assessed. Two reviewers extracted data independently. Studies were pooled, summary receiver operating characteristics curve and diagnostic odds ratio (DOR) with corresponding confidence intervals were calculated. RESULTS: For diagnosis of biliary atresia, ultrasonography (US), hepatic scintigraphy (HBS), and magnetic resonance cholangiography (MRCP) had a pooled sensitivity of 74.9% (range: 70.4%-79.1%), 93.4% (range: 90.3%-95.7%) and 89.7% (range: 84.8%-93.4%), a specificity of 93.4% (range: 91.4%-95.1%), 69.2% (range: 65.1%-73.1%) and 64.7% (range: 58.0%-71.0%), a positive likelihood ratio of 12.16 (range: 6.41-23.08), 3.01 (range: 2.15-4.20) and 3.10 (range: 1.59-6.06), a negative likelihood ratio of 0.23 (range: 0.13-0.38), 0.13 (range: 0.06-0.25) and 0.16 (range: 0.06-0.44), DOR of 72.56 (range: 27.34-192.58), 29.88 (range: 12.82-69.64) and 32.48 (range: 8.22-128.29), with an area under the curve of 0.96, 0.91, and 0.92, and Q value of 0.90, 0.85, and 0.85, respectively. CONCLUSIONS: US, HBS and MRCP can be very useful for the diagnostic work-up of neonatal cholestasis. To improve the sensitivity and specificity, several additional measures can be used. PMID- 26684314 TI - Rectal biopsy for Hirschsprung's disease: a review of techniques, pathology, and complications. AB - BACKGROUND: Hirschsprung's disease (HD) is one of the most common congenital anomalies of colorectal function, affecting approximately 1 in 5000 live births, with a 4:1 male predominance. HD is characterized by aganglionosis that is most often limited to the rectosigmoid, but can extend proximally along the colon and, in rare instances, reach into the small intestine. A clinical history of delayed passage of meconium beyond 48 hours after birth, physical exam findings of abdominal distention and vomiting, and a contrast enema demonstrating a transition zone are highly suggestive of HD. DATA SOURCES: We searched databases including PubMed, Google Scholar, and Scopus for the following key words: Hirschsprung's disease, rectal biopsy, pathology, ganglion cell, nerve trunk hypertrophy, pediatric constipation, and selected publications written in English that were relevant to the scope of this review. RESULTS: Based on the data presented in the literature, we reviewed 1) biopsy techniques for the diagnosis of Hirschsprung's disease, addressed inadequate biopsies, and complications from rectal biopsy, and 2) pathologic and histologic interpretation of biopsy specimens for the diagnosis of Hirschsprung's disease. CONCLUSION: A well executed rectal biopsy with expert pathologic evaluation of the specimen remains the gold standard for the diagnosis of Hirschsprung's disease and is the subject of this review. PMID- 26684315 TI - Detection of respiratory viruses and bacteria in children using a twenty-two target reverse-transcription real-time PCR (RT-qPCR) panel. AB - BACKGROUND: Rapid detection of the wide range of viruses and bacteria that cause respiratory infection in children is important for patient care and antibiotic stewardship. We therefore designed and evaluated a ready-to-use 22 target respiratory infection reverse-transcription real-time polymerase chain reaction (RT-qPCR) panel to determine if this would improve detection of these agents at our pediatric hospital. METHODS: RT-qPCR assays for twenty-two target organisms were dried-down in individual wells of 96 well plates and saved at room temperature. Targets included 18 respiratory viruses and 4 bacteria. After automated nucleic acid extraction of nasopharyngeal aspirate (NPA) samples, rapid qPCR was performed. RT-qPCR results were compared with those obtained by the testing methods used at our hospital laboratories. RESULTS: One hundred fifty nine pediatric NPA samples were tested with the RT-qPCR panel. One or more respiratory pathogens were detected in 132/159 (83%) samples. This was significantly higher than the detection rate of standard methods (94/159, 59%) (P<0.001). This difference was mainly due to improved RT-qPCR detection of rhinoviruses, parainfluenza viruses, bocavirus, and coronaviruses. The panel internal control assay performance remained stable at room temperature storage over a two-month testing period. CONCLUSION: The RT-qPCR panel was able to identify pathogens in a high proportion of respiratory samples. The panel detected more positive specimens than the methods in use at our hospital. The pre made panel format was easy to use and rapid, with results available in approximately 90 minutes. We now plan to determine if use of this panel improves patient care and antibiotic stewardship. PMID- 26684317 TI - Obstructive uropathy and severe acute kidney injury from renal calculi due to adenine phosphoribosyltransferase deficiency. AB - BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is an uncommon genetic cause of chronic kidney disease due to crystalline nephropathy. METHODS: A case of a Chinese boy with APRT deficiency presenting with severe acute kidney injury secondary to obstructive uropathy from multiple renal calculi was reviewed. RESULTS: The patient underwent staged removal of the calculi. Infrared spectrometry of the renal calculi showed 2,8-dihydroxyadenine. APRT deficiency was confirmed with abolished APRT enzyme activity in red blood cells. He was started on allopurinol and low purine diet with complete resolution of the residual calculi. CONCLUSION: APRT deficiency should be considered in patients with multiple radiolucent renal calculi. PMID- 26684316 TI - New technologies as a strategy to decrease medication errors: how do they affect adults and children differently? AB - BACKGROUND: Medication error can occur throughout the drug treatment process, with special relevance in children given the risk of adverse effects resulting from a medication error is more prevalent than in adults. The significance of medication error in children is also greater because small error that would be tolerated in adults can cause significant damage in children. Moreover, the likelihood of injury is higher than in adults. DATA SOURCES: Based on the data published, most medication errors take place in prescribing and administration stages in both populations. Taking in account that child's risk factors are different from those of adults, with some specific causes to pediatrics, we have reviewed available data about new technologies as a strategy to reduce pediatric medication errors. RESULTS: Even though there is a lack of standardized definitions and terminology that makes studies difficult to compare, we checked that new technologies have proven to be effectives in reducing medication errors, mainly computerized physician order entry (CPOE) and platforms to aid decision making. However, we also observed that the use of these informatic tools can also generate new errors. CONCLUSIONS: Implementation of CPOE programs for pediatrics, communication improvement between healthcare professionals taking care of admitted children and the knowledge of these programs should be the mayor priorities for the safety of hospitalized children. PMID- 26684318 TI - Predicting eczema severity beyond childhood. AB - BACKGROUND: We evaluated factors associated with eczema severity in adolescence. METHODS: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test for common food and aeroallergens, highest serum IgE level and eosinophil count were evaluated. Patients with paired NESSs (childhood-NESS is NESS performed at <10 years of age; adolescence-NESS is NESS performed at age >10 years) were further analyzed. RESULTS: Adolescence-NESS (n=383 patients) was associated with eczema onset in infancy, dust mite and food allergen sensitization, dietary avoidance, use of wet wrap, traditional Chinese medicine, immunomodulant (azathioprine or cyclosporine), high IgE level, eosinophil count, but not with family/personal history of atopy. Eighty-two patients had both childhood-NESS and adolescence-NESS (mean follow-up of 6.8 years) showing that adolescence-NESS was associated with childhood- NESS severity grades (P=0.034). Of these patients, 48% remained in the same severity grades, whereas 39% improved, and 13% deteriorated from childhood to adolescence. CONCLUSIONS: It is not possible to assure parents that their child can outgrow eczema. In eczema prognosis research, long-term follow-up is warranted. PMID- 26684319 TI - Effect of zinc supplementation on infants with severe pneumonia. AB - BACKGROUND: Pneumonia is a common respiratory infectious disease in infancy. Previous work shows controversial results on the benefit of zinc supplementation in patients with pneumonia. We conducted this study to investigate serum zinc status amongst infants with severe pneumonia and the clinical impact that zinc supplementation has on those patients with low serum zinc levels. METHODS: This study design was a non-blinded prospective randomized controlled trial. The study is approved by the Ethics Committees of Beijing Children's Hospital. A total of 96 infants diagnosed with severe pneumonia and hospitalized in the pediatric intensive care unit between November 2011 and January 2012 were enrolled. Enrolled patients were divided into low serum zinc and normal serum zinc group. The low serum zinc group was randomized into treatment and control groups. Only the treatment group received zinc supplementation within 48-72 hours after hospitalization. RESULTS: The prevalence of zinc deficiency on admission was 76.0%. The low zinc level was most apparent in infants between 1 and 3 months of age. The serum zinc level increased in the zinc treatment group and returned to a normal level (median, 53.20 MUmol/L) on day 12+/-2. There was no statistical difference in the pediatric critic illness score, lung injury score, length of hospital stay, and duration of mechanical ventilation between the zinc treatment group and control group. CONCLUSION: Zinc deficiency is common in infants with severe pneumonia. Normalization of zinc levels with zinc supplementation did not improve clinical outcomes of infants with pneumonia. PMID- 26684320 TI - Genetic analysis of Italian patients with congenital tufting enteropathy. AB - BACKGROUND: Congenital tufting enteropathy (CTE), an inherited autosomal recessive rare disease, is a severe diarrhea of infancy which is clinically characterized by absence of inflammation and presence of intestinal villous atrophy. Mutations in the EpCAM gene were identified to cause CTE. Recent cases of syndromic tufting enteropathy harboring the SPINT2 (19q13.2) mutation were described. METHODS: Four CTE Italian patients were clinically and immunohistochemically characterized. Direct DNA sequencing of EpCAM and SPINT2 genes was performed. RESULTS: All patients were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, Tyr186Phefs*6 and p.Ile146Asn) in the EpCAM gene; one of them is novel (p.Ile146Asn). Two patients (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third patient (P3) was heterozygous for only one novel EpCAM missense mutation (p.Ile146Asn). In a syndromic patient (P4), no deleterious EpCAM mutation was found. Additional SPINT2 mutational analysis was performed. P4 showed a homozygous SPINT2 mutation (p.Y163C). No SPINT2 mutation was found in P3. CLDN7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identified. CONCLUSION: This study presented a molecular characterization of CTE Italian patients, and identified three mutations in the EpCAM gene and one in the SPINT2 gene. One of EpCAM mutations was novel, therefore increasing the mutational spectrum of allelic variants of the EpCAM gene. Molecular analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation (c.488A>G) recently found to be associated with syndromic CTE subjects. PMID- 26684321 TI - Success in Competition for Space in Two Invasive Coral Species in the western Atlantic - Tubastraea micranthus and T. coccinea. AB - Invasion success by an alien species is dependent upon rate of reproduction, growth, mortality, physical characteristics of the environment, and successful competition for resources with native species. For sessile, epibenthic marine species, one critical resource is space. We examined competitive success in two invasive Indo-Pacific corals involved in competition for space in the northern Gulf of Mexico-Tubastraea coccinea and T. micranthus-on up to 13 offshore oil/gas platforms south of the Mississippi River. Still-capture photos of thousands of overgrowth interactions between the target corals and other sessile epibenthic fauna were analyzed from ROV videos collected at 8-183 m depth. T. micranthus was observed overgrowing >90% of all sessile epibenthic species which it encountered. Frequencies of competitive success varied significantly between platforms. T. coccinea was competitively superior to all competitors pooled, at the 60% level. There was little variability between T. coccinea populations. T. coccinea encountered the following species most frequently-the encrusting sponges Xestospongia sp. (with the commensal Parazoanthus catenularis), X. carbonaria, Dictyonella funicularis, Mycale carmigropila, Phorbas amaranthus, and Haliclona vansoesti-and was found to be, on average, competitively superior to them. Both T. micranthus and T. coccinea appear to be good competitors for space against these species in the northern Gulf of Mexico. Competitive success in T. micranthus was highest in the NE part of the study area, and lowest in the SW area near the Mississippi River plume. T. coccinea's competitive success peaked in the SW study area. This suggests that variation in competitive success both within and between populations of these species may be due to differences in local environmental factors. PMID- 26684322 TI - Studies in the mouse model identify strain variability as a major determinant of disease outcome in Leishmania infantum infection. AB - BACKGROUND: Visceral leishmaniasis is a severe and potentially fatal disease caused by protozoa of the genus Leishmania, transmitted by phlebotomine sandflies. In Europe and the Mediterranean region, L. infantum is the commonest agent of visceral leishmaniasis, causing a wide spectrum of clinical manifestations, including asymptomatic carriage, cutaneous lesions and severe visceral disease. Visceral leishmaniasis is more frequent in immunocompromised individuals and data obtained in experimental models of infection have highlighted the importance of the host immune response, namely the efficient activation of host's macrophages, in determining infection outcome. Conversely, few studies have addressed a possible contribution of parasite variability to this outcome. METHODS: In this study, we compared three isolates of L. infantum regarding their capacity to grow in the organs of mice, the way they activate the host's macrophages and other components of the immune response and also their capacity to cope with host's antimicrobial mechanisms, namely reactive oxygen and nitrogen species. RESULTS: We found that the three parasite strains significantly differed regarding the degree to which they induced nitric oxide synthase (NOS2) and arginase expression in infected macrophages and the pattern of cytokine production they induced in the host, resulting in different degrees of inflammatory response in infected livers. Additionally, the three strains also significantly differed in their in vitro susceptibility to reactive oxygen and nitrogen species. This variability was reflected in the capacity of each strain to persist and proliferate in the organs of wild-type as well as NOS2- and phagocyte oxidase- deficient mice. CONCLUSIONS: The results obtained in this study show that parasite strain variability is an important determinant of disease outcome in L. infantum visceral leishmaniasis, with relevant implications for studies on host-pathogen interaction and also for leishmanicidal drug development. PMID- 26684323 TI - Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. AB - A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs. PMID- 26684324 TI - Analysis of the humoral immune response against the envelope glycoprotein Gc of Schmallenberg virus reveals a domain located at the amino terminus targeted by mAbs with neutralizing activity. AB - Orthobunyaviruses are enveloped viruses that are arthropod-transmitted and cause disease in humans and livestock. Viral attachment and entry are mediated by the envelope glycoproteins Gn and Gc, and the major glycoprotein, Gc, of certain orthobunyaviruses is targeted by neutralizing antibodies. The domains in which the epitopes of such antibodies are located on the glycoproteins of the animal orthobunyavirus Schmallenberg virus (SBV) have not been identified. Here, we analysed the reactivity of a set of mAbs and antisera against recombinant SBV glycoproteins. The M-segment-encoded proteins Gn and Gc of SBV were expressed as full-length proteins, and Gc was also produced as two truncated forms, which consisted of its amino-terminal third and carboxyl-terminal two-thirds. The sera from convalescent animals reacted only against the full-length Gc and its subdomains and not against the SBV glycoprotein Gn. Interestingly, the amino terminal domain of SBV-Gc was targeted not only by polyclonal sera but also by the majority of murine mAbs with a neutralizing activity. Furthermore, the newly defined amino-terminal domain of about 230 aa of the SBV Gc protein could be affinity-purified and further characterized. This major neutralizing domain might be relevant for the development of prophylactic, diagnostic and therapeutic approaches for SBV and other orthobunyaviruses. PMID- 26684325 TI - Epidemiology of Spinal Cord Injury in Iran: Discrepancy with International and Previous Institutional Reports. PMID- 26684327 TI - Ranolazine for the symptomatic treatment of patients with chronic angina pectoris in Greece: a cost-utility study. AB - BACKGROUND: To conduct an economic evaluation comparing ranolazine as add-on therapy to standard-of-care (SoC) with SoC alone in patients with stable angina who did not respond adequately to first line therapy, in Greece. METHODS: A decision tree model was locally adapted in the Greek setting to evaluate the cost utility of ranolazine during a 6-month period. The analysis was conducted from a third-party payer perspective. The clinical inputs were extracted from the published literature. The cost inputs considered in the model reflect drug acquisition, hospitalizations, vascular interventions and monitoring of patients. The resource utilization data were obtained from 3 local experts. All costs refer to the year 2014. Cost-effectiveness was assessed by means of the incremental cost per quality adjusted life year (QALY) gained with the ranolazine as add-on therapy relative to SoC alone (ICER). Probabilistic sensitivity analysis (PSA) was performed. RESULTS: Ranolazine as add-on therapy was more costly compared to SoC alone, as the 6-month total cost per patient was ?1170 and ? 984, respectively. Patients received ranolazine plus SoC and SoC alone gained 0.3155 QALYs and 0.2752 QALYs, respectively. Ranolazine plus SoC resulted in an ICER equal to ?4620 per QALY gained, well below the threshold of ?34,000 per QALY gained. The PSA showed that the likelihood of ranolazine plus SoC being cost effective at the threshold of ?34,000 per QALY gained was 100 %. CONCLUSIONS: Tauhe results suggest that ranolazine as add-on treatment may be a cost-effective alternative for the symptomatic treatment of patients with chronic stable angina in Greece. PMID- 26684326 TI - Physical activity and screen time in adolescents in the chronic kidney disease in children (CKiD) cohort. AB - BACKGROUND: Self-reported physical activity (PA) and screen time exposure in adolescents with chronic kidney disease (CKD) has not been evaluated. METHODS: We performed a cross-sectional analysis of PA and screen time in 224 adolescents at entry into the Chronic Kidney Disease in Children (CKiD) cohort. We compared proportions of CKiD vs. healthy 2012 National Health and Nutrition Examination Survey (NHANES) participants reporting the recommended 60 min of PA 7 days/week or <= 2 h/day of entertainment screen time (binomial probability test). Within CKiD, we assessed correlates of PA and screen time using multivariable logistic and linear regression and examined longitudinal data for 136 participants. RESULTS: Median age of CKiD participants was 15 years, and 60 % were male. Median estimated glomerular filtration rate (eGFR) was 41.3 (IQR 30.8, 52.3) ml/min/1.73 m(2). Only 13 % of CKiD participants met recommendations for PA vs. 25 % of NHANES (p < 0.001), while 98 % in CKiD exceeded the recommended screen time vs. 73 % in NHANES (p < 0.001). Within CKiD, obesity (p = 0.04) and lower eGFR (p = 0.02) were independently associated with greater screen time. CONCLUSIONS: Adolescents with CKD engage in significantly less PA and greater screen time than healthy youth in the United States, and this may worsen over time. PMID- 26684328 TI - Northern Ireland assembly must decide whether to issue new abortion law. PMID- 26684331 TI - Aromatase Inhibitors in the Treatment of Short Stature. AB - Reports published in the 1990s of men with estrogen deficiency caused by defective aromatase or estrogen resistance due to a defective estrogen receptor alpha confirmed the crucial role of estrogen in bone maturation, closure of the epiphyses and cessation of statural growth. Based on these findings, it became reasonable to postulate that selective inhibition of estrogen synthesis with aromatase inhibitors could increase adult height by delaying bone maturation and prolonging the period of growth in males. To date, aromatase inhibitors have been employed in rare pediatric conditions associated with sex steroid excess, and in randomized controlled trials involving boys with short stature and/or constitutional delay of puberty. Findings from these randomized trials suggest that potent aromatase inhibitors increase predicted height, but final adult height data are scarce. Moreover, several safety issues remain inadequately studied. In this paper, published findings on the use of aromatase inhibitors in growth indications are reviewed with emphasis on treatment efficacy and safety. PMID- 26684329 TI - Parturition dysfunction in obesity: time to target the pathobiology. AB - Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms. PMID- 26684333 TI - The Economic Promise of Delayed Aging. AB - Biomedicine has made enormous progress in the last half century in treating common diseases. However, we are becoming victims of our own success. Causes of death strongly associated with biological aging, such as heart disease, cancer, Alzheimer's disease, and stroke-cluster within individuals as they grow older. These conditions increase frailty and limit the benefits of continued, disease specific improvements. Here, we show that a "delayed-aging" scenario, modeled on the biological benefits observed in the most promising animal models, could solve this problem of competing risks. The economic value of delayed aging is estimated to be $7.1 trillion over 50 years. Total government costs, including Social Security, rise substantially with delayed aging--mainly caused by longevity increases--but we show that these can be offset by modest policy changes. Expanded biomedical research to delay aging appears to be a highly efficient way to forestall disease and extend healthy life. PMID- 26684332 TI - p53 and Meduloblastoma. AB - Our understanding of medulloblastoma biology has increased dramatically over the past decade, in part a result of the recognition that there exists tremendous intertumoral heterogeneity not apparent by morphology alone. A particular area that significantly changed our approach to medulloblastoma has been an increased understanding of the role of p53. A role for p53 in medulloblastoma has been established over the past 20 years, however, not until recently has its significance been identified. Recent developments in the understanding of intertumor heterogeneity has clarified the role of TP53 mutations, as the importance of TP53 mutations is highly dependent on the molecular subgroup of medulloblastoma, with TP53 mutant Sonic Hedgehog medulloblastomas forming an extremely high-risk group of patients. As such, there is now a tremendous push to understand the role that p53 plays in treatment resistance of medulloblastoma. In this review, we will summarize the current understanding of p53 in medulloblastoma drawn primarily from recent advances in integrated genomics. PMID- 26684334 TI - The Neonatal Salivary Transcriptome. AB - The ability to noninvasively assess the physical and developmental status of a neonate is a goal of modern medicine. In recent years, technological advances have permitted the high-throughput analysis of saliva for thousands of genes, proteins, and metabolites from a single sample source. Saliva is an ideal biofluid to assess health, disease, and development in the newborn. It may be harnessed repeatedly, even in the most vulnerable patients, without risk of harm. Translating novel information about an infant's global development and risk of disease to the neonatal bedside through the salivary transcriptome has the potential to significantly improve clinical care and outcomes in this at-risk population. PMID- 26684335 TI - Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders. AB - As the ability to identify the contribution of genetic background to human disease continues to advance, there is no discipline of medicine in which this may have a larger impact than in the care of the ill neonate. Newborns with congenital malformations, syndromic conditions, and inherited disorders often undergo an extensive, expensive, and long diagnostic process, often without a final diagnosis resulting in significant health care, societal, and personal costs. Although ethical concerns have been raised about the use of whole-genome sequencing in medical practice, its role in the diagnosis of rare disorders in ill neonates in tertiary care neonatal intensive care units has the potential to augment or modify the care of this vulnerable population of patients. PMID- 26684337 TI - Knowledge on preconceptional folic acid supplementation and intention to seek for preconception care among men and women in an urban city: a population-based cross sectional study. AB - BACKGROUND: To study the knowledge of a large city population on preconception folic acid supplementation and intention to seek for preconception care within an urban perinatal health program. METHODS: Cross-sectional surveys run in Rotterdam, the Netherlands, in 2007 and annually from 2009 to 2014. A random sample of residents aged between 16 and 85 years was taken each year from the municipal population register. Bivariate analysis, interaction analysis, trend analysis and logistic regression were performed. RESULTS: Knowledge on preconceptional folic acid supplementation significantly improved (+20%) between 2007 and 2009, and the intention to consult a GP or midwife in the preconception period significantly increased (+53%) from 2007 to 2012. Logistic regression analyses showed that low socio-economic status was significantly associated with low preconceptional folic acid knowledge, but with higher intention to seek out preconception care. An interaction effect was found between educational level and ethnicity, showing that the higher the educational level the lower the gap of level of knowledge between the different ethnic groups. CONCLUSION: Despite campaigns about folic acid supplementation knowledge on this supplement remains low. The intention amongst men and women to seek out preconception care is still insufficient. Structural interventions to increase and maintain awareness on folic acid supplementation, especially among high-risk groups, are needed. PMID- 26684338 TI - Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles. AB - Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy). PMID- 26684336 TI - Immunity and Inflammation in Epilepsy. AB - This review reports the available evidence on the activation of the innate and adaptive branches of the immune system and the related inflammatory processes in epileptic disorders and the putative pathogenic role of inflammatory processes developing in the brain, as indicated by evidence from experimental and clinical research. Indeed, there is increasing knowledge supporting a role of specific inflammatory mediators and immune cells in the generation and recurrence of epileptic seizures, as well as in the associated neuropathology and comorbidities. Major challenges in this field remain: a better understanding of the key inflammatory pathogenic pathways activated in chronic epilepsy and during epileptogenesis, and how to counteract them efficiently without altering the homeostatic tissue repair function of inflammation. The relevance of this information for developing novel therapies will be highlighted. PMID- 26684340 TI - Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1. PMID- 26684341 TI - Demonstration of lignin-to-peroxidase direct electron transfer. A TRANSIENT-STATE KINETICS, DIRECTED MUTAGENESIS, EPR AND NMR STUDY. PMID- 26684339 TI - Regionally-derived cell populations and skeletal stem cells from human foetal femora exhibit specific osteochondral and multi-lineage differentiation capacity in vitro and ex vivo. AB - BACKGROUND: Adult skeletal stem cells (SSCs) often exhibit limited in vitro expansion with undesirable phenotypic changes and loss of differentiation capacity. Foetal tissues offer an alternative cell source, providing SSCs which exhibit desirable differentiation capacity over prolonged periods, ideal for extensive in vitro and ex vivo investigation of fundamental bone biology and skeletal development. METHODS: We have examined the derivation of distinct cell populations from human foetal femora. Regionally isolated populations including epiphyseal and diaphyseal cells were carefully dissected. Expression of the SSC marker Stro-1 was also found in human foetal femora over a range of developmental stages and subsequently utilised for immuno-selection. RESULTS: Regional populations exhibited chondrogenic (epiphyseal) and osteogenic (diaphyseal) phenotypes following in vitro and ex vivo characterisation and molecular analysis, indicative of native SSC maturation during skeletal development. However, each population exhibited potential for induced multi-lineage differentiation towards bone (bone nodule formation), cartilage (proteoglycan and mucopolysaccharide deposition) and fat (lipid deposition), suggesting the presence of a shared stem cell sub-population. This shared sub-population may be comprised of Stro-1+ cells, which were later identified and immuno-selected from whole foetal femora exhibiting multi-lineage differentiation capacity in vitro and ex vivo. CONCLUSIONS: Distinct populations were isolated from human foetal femora expressing osteochondral differentiation capacity. Stro-1 immuno-selected SSCs were isolated from whole femora expressing desirable multi-lineage differentiation capacity over prolonged in vitro expansion, superior to their adult-derived counterparts, providing a valuable cell source with which to study bone biology and skeletal development. PMID- 26684342 TI - Screening Breast MRI in Women with a Personal History of Breast Cancer. PMID- 26684343 TI - Synthesis, Characterization, and Preclinical Evaluation of (99m)Tc-Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer. AB - The novel tetraaza macrobicyclic chelator 3,6,9,15 tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione (TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos 1(21),17,19-triene-2,7,11,16-tetradione (OPTT) were synthesized, characterized, and radiolabeled with (99m)Tc to produce (99m)Tc-TBPD and (99m)Tc-OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of (99m)Tc-TBPD and (99m)Tc-OPTT was found 98% and 97%. In vitro serum stability of (99m)Tc-TBPD was found to be 95.2%, while that of (99m)Tc-OPTT 94.2% up to 24 h. Blood kinetics experiments of (99m)Tc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 +/- 0.89% activity of (99m)Tc-TBPD and 99.42 +/- 0.88% activity of (9m)Tc-OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of (99m) Tc-TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of (99m)Tc-OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of (99m)Tc-TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of (99m)Tc OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines. PMID- 26684344 TI - A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex. AB - Mutations in subunits of the SWI/SNF chromatin remodelling complex are found in 20 % of human cancers. At face value, this would appear to indicate that this multiprotein complex is a potent tumour suppressor. However, it has recently emerged that some mutations in the SWI/SNF complex can have a gain-of-function effect and that in other tumours, such as pancreatic cancer, leukaemia, and breast cancer, the wild-type complex is used to drive cancer. Thus, paradoxically, this "tumour suppressor" has become an attractive target for developing anticancer agents. The SWI/SNF complex makes several protein-protein interactions both within the complex and with a wide range of transcription factors, and targeting these protein-protein interactions is emerging as the best approach to modulating the activity of the complex selectively. PMID- 26684345 TI - Initial experience with imaging of the lower extremity arteries in an open 1.0 Tesla MRI system using the triggered angiography non-contrast-enhanced sequence (TRANCE) compared to digital subtraction angiography (DSA). AB - PURPOSE: The aim of this study was to evaluate the feasibility and validity of arterial lower limb imaging with triggered angiography non-contrast enhanced (TRANCE) in an open MRI at 1.0 Tesla (T) compared to digital subtraction angiography (DSA). MATERIAL AND METHODS: ECG-gated, non-contrast-enhanced magnetic resonance angiography (MRA) was performed in a 1.0-T high-field open magnetic resonance imaging (MRI) system which generates a vertical magnetic field. Three acquisition levels were defined (abdominal and pelvic level, arterial segments above the knee and segments below the knee) and a total of 1782 vessel diameter measurements were taken on a total of 11 patients with suspected peripheral arterial occlusive disease (PAOD) (8 men, 3 women; average age 66 years). In each patient, 162 vessel segments (81 each with TRANCE and DSA) were defined and measured. Pearson correlation coefficients were calculated. RESULTS: At the abdominal/pelvic level, all mean values measured with DSA exceeded the mean values obtained with TRANCE. Above the knee, mean vessel diameters were measured smaller in DSA in six, equal in three, and larger in two vessel segments. Below the knee, all measured averages, except for the tibiofibular tract (TFT) measurements, were larger in TRANCE. In total, two small (<=0.3), two moderate (>0.3), 11 good (>0.5), 10 high (>0.7) and 13 very high (>0.8) correlations were obtained. CONCLUSIONS: Non-contrast-enhanced imaging of the lower limb arteries using a TRANCE-sequence in a 1.0 T open MRI system is feasible with the protocol presented; however, TRANCE tends to underestimate larger vessels and overestimate smaller vessels compared to DSA. PMID- 26684346 TI - Measuring multiple neuromuscular activation using EMG - a generalizability analysis. AB - Analysis of electromyography (EMG) data has been shown to be valuable in biomedical and clinical research. However, most analysis tools do not consider the non-linearity of EMG data or the synergistic effects of multiple neuromuscular activities. The SYNERGOS algorithm was developed to assess a single index based on non-linear analysis of multiple neuromuscular activation (MNA) of different muscles. This index has shown promising results in Parkinsonian gait, but it was yet to be explored whether the SYNERGOS index is generalizable. In this study, we evaluated generalizability of the SYNERGOS index over the course of several trials and over separate days with different walking speeds. Ten healthy adults aged from 18 to 40 years walked on a treadmill on two different days, while EMG data was collected from the upper and lower right leg. SYNERGOS indices were obtained and a generalizability analysis was conducted. The algorithm detected changes in MNA in response to altering gait speed and depicted a high generalizability coefficient ( rho^2 ${?hat ?rho ^2}$ ) of 0.823 with a standard error of 5.117 with nominal inter-trial or inter-day effects. We concluded SYNERGOS may be a valuable tool in EMG analysis due to its generalizability and its sensitivity to task modifications and associated neuromotor changes. PMID- 26684347 TI - Adhesion and proliferation of cells and bacteria on microchip with different surfaces microstructures. AB - Surface microstructure of implant materials is an essential factor for soft tissue healing around the implant. The purpose of this study was to explore the effect of different microchip surface microstructures on the adhesion and proliferation of cells and bacteria. Hydroxyapatite (HA) microchips with different microstructures (linear, decussate, circular and triangular) and their polydimethylsiloxane (PDMS) replica chips were prepared. Myoblast cells (C2C12), Staphylococcus aureus and Porphyromonas gingivalis were seeded on these chips to investigate the effect of different surface microstructures on the adhesion and proliferation. The results indicated that different surface microstructure in the same size did not show much difference on adhesion and proliferation of cell and bacteria; compared to microstructure region (grain ca. 2 MUm), the cells preferred to adhesion and proliferate in the blank area (grain ca. 260 nm), in contrast, the bacteria were significantly preferable to the microstructure regions. In conclusion, it might be better for the implant materials to be manufactured in submicron-scale rather than micro-scale to improve the proliferation of cells and to inhibit the adhesion and growth of bacteria. PMID- 26684348 TI - Assessment of calibration methods on impedance pneumography accuracy. AB - The aim was to assess accuracy of tidal volumes (TV) calculated by impedance pneumography (IP), reproducibility of calibration coefficients (CC) between IP and pneumotachometry (PNT), and their relationship with body posture, breathing rate and depth. Fourteen students performed three sessions of 18 series: normal and deep breathing at 6, 10, 15 breaths/min rates, while supine, sitting and standing; 18 CC were calculated for every session. Session 2 was performed 2 months after session 1, session 3 1-3 days after session 2. TV were calculated using full or limited set of CC from current session, in case of sessions 2 and 3 also using CC from session 1 and 2, respectively. When using full set of CC from current session, IP underestimated TV by -3.2%. Using CC from session 2 for session 3 measurements caused decrease of relative difference: -3.9%, from session 1 for session 2: -5.3%; for limited set of CC: -5.0%. The body posture had significant effect on CC. The highest accuracy was obtained when all factors influencing CC were considered. The application of CC related only to body posture may result in shortening of calibration and moderate accuracy loss. Using CC from previous session compromises accuracy moderately. PMID- 26684349 TI - Failure analysis of ParaPost drills that fractured in service: a retrieval analysis study. AB - The aim was to determine the fracture mechanism of two clinically failed ParaPost drills. First, the fracture planes were analyzed by scanning electron microscopy (SEM). The drill end of one of the fractured pieces of each drill was then embedded in resin and after being metallographically ground and polished, was chemically etched. The microstructure and elemental composition were then examined by SEM/EDS analysis while hardness was determined with a Vickers testing device. Fractographic analysis revealed that both drills failed in a brittle manner and showed a pattern characteristic of a quasi-cleavage fracture mode. SEM and EDS analysis revealed a random distribution of a second phase enriched in Mo, W, and V, probably appended to (Mo, W, V)*C carbides, while the alloy composition is similar to M3 tool steel, a high-speed molybdenum tool steel. The microhardness of a ParaPost Drill #1 was found to be HV 862+/-29 and that for a Drill #2 was 846+/-16, with no significant differences (p>0.05). In both cases, fracture originated from surface points acting as stress concentrators and facilitating brittle fracture in the quasi-cleavage mode indicating that failure rate might be further minimized by a better instrument design. PMID- 26684350 TI - Comparison of FreeliteTM and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis. AB - BACKGROUND: Quantification of serum free light chains (FLC) is important in the diagnosis of plasma cell diseases where an abnormal kappa:lambda ratio infers a population of monoclonal plasma cells. The FreeliteTM and N Latex assays have been validated in populations without kidney disease but there is a paucity of data relating to the use of these assays in end stage kidney disease (ESKD). The aim of the study was to compare FLC assay performance in ESKD patients on haemodialysis. METHODS: Cross-sectional multi-centre study comparing the performance of the two assays on 112 haemodialysis patients without known paraproteinaemia. We quantified FLC pre- and post-dialysis using both the N Latex and the Freelite assays. RESULTS: FLC levels were elevated by both assays. Lambda FLC levels were considerably higher by the N Latex assay. Using the proposed renal reference range for Freelite (0.37-3.1) all but one patient had normal kappa:lambda FLC ratios. In contrast, there were no abnormal FLC ratios pre dialysis using the N Latex assay. This was due to lambda FLC reading significantly higher by the N Latex assay. Kappa and lambda FLC levels decreased with dialysis but remained elevated above the normal range. The excess of lambda FLC by N Latex persisted post-dialysis but was somewhat attenuated. Dialysis adequacy and dialysis modality predicted clearance of kappa and lambda FLC by both assays. CONCLUSIONS: The N Latex assay reported significantly higher pre dialysis lambda FLC concentrations compared with the Freelite assays. Clinicians should be aware of the need for a separate renal reference range for interpreting FLC ratio using the Freelite assay but not for the N Latex assay in ESKD patients. PMID- 26684351 TI - Bisalbuminemia accompanying bisalbuminuria detected in capillary electrophoresis, not in gel electrophoresis. PMID- 26684352 TI - Ghrelin action on GnRH neurons and pituitary gonadotropes might be mediated by GnIH-GPR147 system. AB - Acylated ghrelin (AG) effect on GnRH secretion is mediated, at least in part, by GH secreta-gogue receptor (GHS-R) which is present in the GnRH neurons. As the acylation is mandatory for binding to GHS-R, unacylated isoform of ghrelin (UAG) action on gonadotropin secretion is likely to be mediated by other receptors or mediators that have not been identified yet. UAG, therefore, may act partially via a GHS-R-independent mechanism and inhibitory impact of UAG on GnRH neurons may be executed via modulation of other neuronal networks. Ghrelin and gonadotropin inhibitory hormone (GnIH), two agonistic peptides, have been known as important regulators of reproductive events. Potential impact of ghrelin on the activity of GnIH neurons is not exactly known. Both GnIH and ghrelin are potent stimulators of food intake and inhibitors of gonadotropin release. By binding G-protein coupled GnIH receptor (GnIH-R), GPR147, which is located in the human gonadotropes and GnRh neurons, GnIH exerts an inhibitory effect on both GnRH neurons and the gonadotropes. The GnIH-GPR147 system receives information regarding the status of energy reservoir of body from circulating peptides and then transfers them to the kisspeptin-GnIH-GnRH network. Due to wide distribution of this network in brain GnIH neurons may project on ghrelin neurons in the arcuate nucleus and contribute to the regulation of UAG's central effects or vice versa. Together, the unidentified ghrelin receptor in the hypothalamus and hypophysis may be GnIH-R. Therefore, it is reasonable that ghrelin may act on both hypothalamus and hypophysis via GnIH-GPR147 system to block gonadotropin synthesis and secretion. PMID- 26684353 TI - Use of hydroxyprogesterone caproate to prevent preterm labour in uterine didelphys: a case report. AB - Congenital uterine anomalies have been associated with poor reproductive outcome, which include recurrent miscarriage, abruptio placenta, intra-uterine growth restriction and preterm delivery. Here, we report a case: 36 years old, G3P2, known case of uterine didelphys, with history of preterm birth, who successfully carried her pregnancy till term with weekly intramuscular injection of 250 mg hydroxyprogesterone caproate ((r)Proluton Depot, Zuellig Pharma). PMID- 26684354 TI - Editorial overview: Genomes and evolution: "Seq-ing" answers in life's genomes. PMID- 26684355 TI - "Why are you pregnant? What were you thinking?": How women navigate experiences of HIV-related stigma in medical settings during pregnancy and birth. AB - Having children is a growing reality for women living with HIV in Canada. It is imperative to understand and respond to women's unique experiences and psychosocial challenges during pregnancy and as mothers including HIV-related stigma. This qualitative study used a narrative methodological approach to understand women's experiences of HIV-related stigma as they navigate health services in pregnancy (n = 66) and early postpartum (n = 64). Narratives of women living with HIV expose the spaces where stigmatizing practices emerge as women seek perinatal care and support, as well as highlight the relationship between HIV-related stigma and disclosure, and the impact this has on women's pregnancy and birthing experiences. PMID- 26684356 TI - The B56gamma3 regulatory subunit-containing protein phosphatase 2A outcompetes Akt to regulate p27KIP1 subcellular localization by selectively dephosphorylating phospho-Thr157 of p27KIP1. AB - The B56gamma-containing protein phosphatase 2A (PP2A-B56gamma) has been postulated to have tumor suppressive functions. Here, we report regulation of p27KIP1 subcellular localization by PP2A-B56gamma3. B56gamma3 overexpression enhanced nuclear localization of p27KIP1, whereas knockdown of B56gamma3 decreased p27KIP1 nuclear localization. B56gamma3 overexpression decreased phosphorylation at Thr157 (phospho-Thr157), whose phosphorylation promotes cytoplasmic localization of p27KIP1, whereas B56gamma3 knockdown significantly increased the level of phospho-Thr157. In vitro, PP2A-B56gamma3 catalyzed dephosphorylation of phospho-Thr157 in a dose-dependent and okadaic acid sensitive manner. B56gamma3 did not increase p27KIP1 nuclear localization by down regulating the upstream kinase Akt activity and outcompeted a myristoylated constitutively active Akt (Aktca) in regulating Thr157 phosphorylation and subcellular localization of p27KIP1. In addition, results of interaction domain mapping revealed that both the N-terminal and C-terminal domains of p27 and a domain at the C-terminus of B56gamma3 are required for interaction between p27 and B56gamma3. Furthermore, we demonstrated that p27KIP1 levels are positively correlated with B56gamma levels in both non-tumor and tumor parts of a set of human colon tissue specimens. However, positive correlation between nuclear p27KIP1 levels and B56gamma levels was found only in the non-tumor parts, but not in tumor parts of these tissues, implicating a dysregulation in PP2A-B56gamma3 regulated p27KIP1 nuclear localization in these tumor tissues. Altogether, this study provides a new mechanism by which the PP2A-B56gamma3 holoenzyme plays its tumor suppressor role. PMID- 26684357 TI - Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy. AB - Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine. PMID- 26684358 TI - MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of beta-catenin signaling. AB - Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through beta-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and beta-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC. PMID- 26684361 TI - Electron beam damage in oxides: a review. AB - This review summarizes a variety of beam damage phenomena relating to oxides in (scanning) transmission electron microscopes, and underlines the shortcomings of currently popular mechanisms. These phenomena include mass loss, valence state reduction, phase decomposition, precipitation, gas bubble formation, phase transformation, amorphization and crystallization. Moreover, beam damage is also dependent on specimen thickness, specimen orientation, beam voltage, beam current density and beam size. This article incorporates all of these damage phenomena and experimental dependences into a general description, interpreted by a unified mechanism of damage by induced electric field. The induced electric field is produced by positive charges, which are generated from excitation and ionization. The distribution of the induced electric fields inside a specimen is beam illumination- and specimen-shape- dependent, and associated with the experimental dependence of beam damage. Broadly speaking, the mechanism operates differently in two types of material. In type I, damage increases the resistivity of the irradiated materials, and is thus divergent, resulting in phase separation. In type II, damage reduces the resistivity of the irradiated materials, and is thus convergent, resulting in phase transformation. Damage by this mechanism is dependent on electron-beam current density. The two experimental thresholds are current density and irradiation time. The mechanism comes into effect when these thresholds are exceeded, below which the conventional mechanisms of knock-on and radiolysis still dominate. PMID- 26684359 TI - Hyaluronan stimulates pancreatic cancer cell motility. AB - Hyaluronan (HA) accumulates in pancreatic ductal adenocarcinoma (PDAC), but functional significance of HA in the aggressive phenotype remains unknown. We used different models to investigate the effect of HA on PDAC cell motility by wound healing and transwell migration assay. Changes in cell motility were examined in 8 PDAC cell lines in response to inhibition of HA production by treatment with 4-methylumbelliferone (4-MU) and to promotion by treatment with 12 O-tetradecanoyl-phorbol-13-acetate (TPA) or by co-culture with tumor-derived stromal fibroblasts. We also investigated changes in cell motility by adding exogenous HA. Additionally, mRNA expressions of hyaluronan synthases and hyaluronidases were examined using real time RT-PCR. Inhibition of HA by 4-MU significantly decreased the migration, whereas promotion of HA by TPA or co culture with tumor-derived fibroblasts significantly increased the migration of PDAC cells. The changes in HA production by these treatments tended to be associated with changes in HAS3 mRNA expression. Furthermore, addition of exogenous HA, especially low-molecular-weight HA, significantly increased the migration of PDAC cells. These findings suggest that HA stimulates PDAC cell migration and thus represents an ideal therapeutic target to prevent invasion and metastasis. PMID- 26684360 TI - Curriculum, Practice, and Diet Predict Health Among Experienced Taiji and Qigong Practitioners. AB - OBJECTIVE: To explore the potential influence of curriculum, frequency of practice, and dietary quality on the health of experienced Taiji and qigong practitioners. DESIGN: Theoretical and cross-sectional study. METHODS: Responses from a volunteer sample of Taiji practitioners from across the United States were collected using an online survey. The instrument was designed to collect data on health-related quality of life, diet, and Taiji practice regimens. All experienced (>=4 years) practitioners (n = 94; mean age, 55.82 years [range, 24 83 years]) were included in the analysis. Relationships among self-reported health, diet, experience, practice frequency, and curricular complexity were analyzed. RESULTS: Practitioners' health status did not show the typical negative association with age and was positively associated with complex curricula, practice, and high-quality diets. Significant interaction effects were seen between (1) curricular complexity and additional practice (p < 0.05) and (2) curricular complexity and diet (p < 0.05). CONCLUSIONS: Intervention designers, Taiji teachers, and practitioners should consider the potential influence of curricula, out-of-class practice, and healthy diets for optimizing health-related gains and minimizing age-related losses in interventions and community-based programs. PMID- 26684363 TI - Who is becoming personality disordered? A register-based follow-up study of 508 inpatient adolescents. AB - BACKGROUND: Our aim was to investigate which clinical and socio-demographic factors among adolescent psychiatric patient aged 13-17 are associated with a diagnosis of personality disorder (PD) in young adulthood after discharge from psychiatric hospitalization. METHODS: The study sample consisted of 508 adolescents (ages 13-17) admitted to acute psychiatric impatient care between April 2001 and March 2006. DSM IV-based psychiatric diagnoses were obtained from the Schedule for Affective Disorder and Schizophrenia for School-Age Children Present and Lifetime (K-SADS-PL). The information on hospital treatments either in out- or inpatient settings until the end of 2012 was extracted from the national Care Register for Health Care provided by the Finnish National Institute for Health and Welfare. The follow-up time was 9.2 years (mean, 95% CI 9.0-9.3 yrs). RESULTS: Altogether 57 (11.2%) of subjects were diagnosed PD in adulthood. Among girls with anxiety disorders in adolescence the risk for PD in adulthood increased to 4.39-fold (95% CI 2.02-9.53). Males with later PD were more likely to be admitted for hospital treatment from child welfare placements (OR 3.23, 95% CI 1.21-8.61). However, axis I disorders in adolescence was not associated with risk for PD among boys. CONCLUSIONS: The results indicate that risk of PD developing later in life is increased among girls with anxiety disorders. A child welfare placement associated with PD in males later in life. These associations in adolescents should be considered in clinical work. PMID- 26684362 TI - A novel technique for quantitative bedside monitoring of neurovascular coupling. AB - BACKGROUND: There is no current method for continuous quantification of neurovascular coupling (NVC) in spontaneous brain activity. To fill this void, we propose a novel method to quantify NVC using electroencephalogram (EEG) and near infrared spectroscopy (NIRS) data. NEW METHOD: Since EEG and NIRS measure physiologic changes occurring at different time scales, we bring them into a common dynamical time frame (DTF). To achieve this, we partition both signals into one-second epochs and calculate the standard deviation of the EEG and the average value of the NIRS for each epoch. We then quantify the NVC by calculating spectral coherence between the two signals in the DTF. The resulting NVC will have a low resolution with all of its content localized below 1Hz. RESULTS: After validating this framework on simulated data, we applied this approach to EEG and NIRS signals collected from four term infants undergoing therapeutic hypothermia for neonatal encephalopathy. Two of these infants showed no evidence of structural brain injury, and the other two died during the course of the therapy. The intact survivors showed emergence of NVC during hypothermia and/or after rewarming. In contrast, the two critically ill infants, who subsequently died, lacked this feature. COMPARISON WITH EXISTING METHODS: Existing methods quantify NVC by averaging neurovascular signals based on certain events (for example seizure) in the EEG activity, whereas our approach quantifies coupling between spontaneous background EEG and NIRS. CONCLUSION: Real-time continuous monitoring of NVC may be a promising physiologic signal for cerebral monitoring in future. PMID- 26684365 TI - The capillary bridge between two spheres: New closed-form equations in a two century old problem. AB - We discuss progress in obtaining explicit equations for the capillary force between nano and micron sized solid spheres. Early approaches to this two-century old problem adopted approximations to the geometry. With the toroidal approximation, the meridian profile is approximated by an arc, and the approach leads to the capillary force being dependent on the location at which the force is evaluated. The Derjaguin approximation further assumes that the meridian radius is orders of magnitude smaller than the azimuth radius. An explicit expression for the capillary force is obtained, but the equation is limited to sufficiently small liquid volumes and separation distances. Significant progress has been made in recent years in using numerical solutions to derive analytical expressions for capillary bridges. Early numerical investigation established that the maximum separation for stable capillary bridges before rupture scales to the cubic root of the liquid volume. We report new progress in using numerical solutions to obtain more accurate and more general closed-form expressions for capillary bridges. Simple explicit algebraic equations have been observed to fit the numerical results well, leading to a closed-form solution applicable to capillary bridges between equal and unequal spheres and with zero or finite solid liquid contact angles. The newly derived closed-form equation is more accurate and reduces to the Derjaguin equation when the liquid volume (or half-filling angle) and separation distance are both sufficiently small. PMID- 26684364 TI - The effect of multivalent cations and Tau on paclitaxel-stabilized microtubule assembly, disassembly, and structure. AB - In this review we describe recent studies directed at understanding the formation of novel nanoscale assemblies in biological materials systems. In particular, we focus on the effects of multivalent cations, and separately, of microtubule associated protein (MAP) Tau, on microtubule (MT) ordering (bundling), MT disassembly, and MT structure. Counter-ion directed bundling of paclitaxel stabilized MTs is a model electrostatic system, which parallels efforts to understand MT bundling by intrinsically disordered proteins (typically biological polyampholytes) expressed in neurons. We describe studies, which reveal an unexpected transition from tightly spaced MT bundles to loose bundles consisting of strings of MTs as the valence of the cationic counter-ion decreases from Z=3 to Z=2. This transition is not predicted by any current theories of polyelectrolytes. Notably, studies of a larger series of divalent counter-ions reveal strong ion specific effects. Divalent counter-ions may either bundle or depolymerize paclitaxel-stabilized MTs. The ion concentration required for depolymerization decreases with increasing atomic number. In a more biologically related system we review synchrotron small angle x-ray scattering (SAXS) studies on the effect of the Tau on the structure of paclitaxel-stabilized MTs. The electrostatic binding of MAP Tau isoforms leads to an increase in the average radius of microtubules with increasing Tau coverage (i.e. a re-distribution of protofilament numbers in MTs). Finally, inspired by MTs as model nanotubes, we briefly describe other more robust lipid-based cylindrical nanostructures, which may have technological applications, for example, in drug encapsulation and delivery. PMID- 26684366 TI - Clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis from a center with a high MRSA prevalence. AB - BACKGROUND: We describe the clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis (CF) from the U.S. CF center with the highest MRSA prevalence. METHODS: Medical records of children with CF were retrospectively reviewed from 1997-2009. MRSA clinical isolates from 2007-2009 were analyzed by polymerase chain reaction and pulsed field gel electrophoresis. RESULTS: The prevalence of MRSA was 1% in 1997 and 49% in 2009. Fifty-five children (26%) had persistent MRSA infection. Sixty-eight percent of MRSA isolates were hospital-associated (HA) MRSA, of which 52% were pulsed-field type USA 100. Ninety-three percent of HA MRSA isolates were clindamycin resistant. Twelve children acquired MRSA before 1 year of age, 83% of whom were hospitalized prior to acquisition of MRSA. Ten of 11 sibling pairs carried indistinguishable MRSA strains. Children with persistent MRSA were hospitalized more often (P = .01), required inhaled medications more frequently (P = .01), and had higher rates of Pseudomonas aeruginosa coinfection (P < .001). CONCLUSION: MRSA prevalence in children with CF is increasing, and most children are infected with HA MRSA. Exposure to health care facilities and gastrointestinal surgeries may facilitate early acquisition of MRSA. Siblings carry indistinguishable MRSA strains, indicating household transmission of MRSA. Children with persistent MRSA had worse pulmonary morbidity. Coinfection with MRSA and P aeruginosa is likely associated with further increased pulmonary morbidity. PMID- 26684367 TI - Postdischarge decontamination of MRSA, VRE, and Clostridium difficile isolation rooms using 2 commercially available automated ultraviolet-C-emitting devices. AB - BACKGROUND: Two ultraviolet-C (UVC)-emitting devices were evaluated for effectiveness in reducing methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile (CD). METHODS: Six surfaces in rooms previously occupied by patients with MRSA, VRE, or CD were cultured before and after cleaning and after UVC disinfection. In a parallel laboratory study, MRSA and VRE suspended in trypticase soy broth were inoculated onto stainless steel carriers in triplicate, placed in challenging room areas, subjected to UVC, and subcultured to detect growth. RESULTS: Sixty-one rooms and 360 surfaces were assessed. Before cleaning, MRSA was found in 34.4%, VRE was found in 29.5%, and CD was found in 31.8% of rooms. Cleaning reduced MRSA-, VRE-, and CD-contaminated rooms to 27.9%, 29.5%, and 22.7%, respectively (not statistically significant). UVC disinfection further reduced MRSA-, VRE-, and CD contaminated rooms to 3.3% (P = .0003), 4.9% (P = .0003), and 0% (P = .0736), respectively. Surface colony counts (excluding floors) decreased from 88.0 to 19.6 colony forming units (CFU) (P < .0001) after manual cleaning; UVC disinfection further reduced it to 1.3 CFU (P = .0013). In a multivariable model of the carrier study, the odds of detecting growth in broth suspensions after UVC disinfection were 7 times higher with 1 machine (odds ratio, 6.96; 95% confidence interval, 3.79-13.4) for a given organism, surface, and concentration. CONCLUSIONS: UVC devices are effective adjuncts to manual cleaning but vary in their ability to disinfect high concentrations of organisms in the presence of protein. PMID- 26684368 TI - Multicenter study of device-associated infection rates in hospitals of Mongolia: Findings of the International Nosocomial Infection Control Consortium (INICC). AB - BACKGROUND: To report the results of the International Nosocomial Infection Control Consortium (INICC) multicenter study conducted in Mongolia from September 2013-March 2015. METHODS: A device-associated health care-associated infection prospective surveillance study in 3 adult intensive care units (ICUs) from 3 hospitals using the U.S. Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) definitions and INICC methods. RESULTS: We documented 467 ICU patients for 2,133 bed days. The central line-associated bloodstream infection (CLABSI) rate was 19.7 per 1,000 central line days, the ventilator-associated pneumonia (VAP) rate was 43.7 per 1,000 mechanical ventilator days, and the catheter-associated urinary tract infection (CAUTI) rate was 15.7 per 1,000 urinary catheter days; all of the rates are higher than the INICC rates (CLABSI: 4.9; VAP: 16.5; and CAUTI: 5.3) and CDC-NHSN rates (CLABSI: 0.8; VAP: 1.1; and CAUTI: 1.3). Device use ratios were also higher than the CDC NHSN and INICC ratios, except for the mechanical ventilator device use ratio, which was lower than the INICC ratio. Resistance of Staphylococcus aureus to oxacillin was 100%. Extra length of stay was 15.1 days for patients with CLABSI, 7.8 days for patients with VAP, and 8.2 days for patients with CAUTI. Extra crude mortality in the ICUs was 18.6% for CLABSI, 17.1% for VAP, and 5.1% for CAUTI. CONCLUSION: Device-associated health care-associated infection rates and most device use ratios in our Mongolian hospitals' ICUs are higher than the CDC-NSHN and INICC rates. PMID- 26684369 TI - Impact of pulsed xenon ultraviolet light on hospital-acquired infection rates in a community hospital. AB - BACKGROUND: The role of contaminated environments in the spread of hospital associated infections has been well documented. This study reports the impact of a pulsed xenon ultraviolet no-touch disinfection system on infection rates in a community care facility. METHODS: This study was conducted in a community hospital in Southern Florida. Beginning November 2012, a pulsed xenon ultraviolet disinfection system was implemented as an adjunct to traditional cleaning methods on discharge of select rooms. The technology uses a xenon flashlamp to generate germicidal light that damages the DNA of organisms in the hospital environment. The device was implemented in the intensive care unit (ICU), with a goal of using the pulsed xenon ultraviolet system for disinfecting all discharges and transfers after standard cleaning and prior to occupation of the room by the next patient. For all non-ICU discharges and transfers, the pulsed xenon ultraviolet system was only used for Clostridium difficile rooms. Infection data were collected for methicillin-resistant Staphylococcus aureus, C difficile, and vancomycin resistant Enterococci (VRE). The intervention period was compared with baseline using a 2-sample Wilcoxon rank-sum test. RESULTS: In non-ICU areas, a significant reduction was found for C difficile. There was a nonsignificant decrease in VRE and a significant increase in methicillin-resistant S aureus. In the ICU, all infections were reduced, but only VRE was significant. This may be because of the increased role that environment plays in the transmission of this pathogen. Overall, there were 36 fewer infections in the whole facility and 16 fewer infections in the ICU during the intervention period than would have been expected based on baseline data. CONCLUSION: Implementation of pulsed xenon ultraviolet disinfection is associated with significant decreases in facility wide and ICU infection rates. These outcomes suggest that enhanced environmental disinfection plays a role in the risk mitigation of hospital-acquired infections. PMID- 26684370 TI - Silk Fibroin for Flexible Electronic Devices. AB - Flexible electronic devices are necessary for applications involving unconventional interfaces, such as soft and curved biological systems, in which traditional silicon-based electronics would confront a mechanical mismatch. Biological polymers offer new opportunities for flexible electronic devices by virtue of their biocompatibility, environmental benignity, and sustainability, as well as low cost. As an intriguing and abundant biomaterial, silk offers exquisite mechanical, optical, and electrical properties that are advantageous toward the development of next-generation biocompatible electronic devices. The utilization of silk fibroin is emphasized as both passive and active components in flexible electronic devices. The employment of biocompatible and biosustainable silk materials revolutionizes state-of-the-art electronic devices and systems that currently rely on conventional semiconductor technologies. Advances in silk-based electronic devices would open new avenues for employing biomaterials in the design and integration of high-performance biointegrated electronics for future applications in consumer electronics, computing technologies, and biomedical diagnosis, as well as human-machine interfaces. PMID- 26684371 TI - Development and Validation of the Maternal and Partner Sex During Pregnancy Scales. AB - Little is known about current attitudes in the United States toward having sex during pregnancy. It is possible that pregnant women and their sexual partners hold beliefs and have feelings during this time that might lead to sexual and relational distress. Two new scales, Maternal Sex During Pregnancy and Partner Sex During Pregnancy, were developed and administered to 112 newly pregnant couples. The scales demonstrated strong reliability and validity. Attitudes and beliefs varied across the sample, but the scores did not significantly differ between partners. These scales allow clinicians to support healthy sexuality during pregnancy by understanding sources of anxiety and possible misconceptions. PMID- 26684389 TI - Planned caesarean section for women with a twin pregnancy. AB - BACKGROUND: Twin pregnancies are associated with increased perinatal mortality, mainly related to prematurity, but complications during birth may contribute to perinatal loss or morbidity. The option of planned caesarean section to avoid such complications must therefore be considered. On the other hand, randomised trials of other clinical interventions in the birth process to avoid problems related to labour and birth (planned caesarean section for breech, and continuous electronic fetal heart rate monitoring), have shown an unexpected discordance between short-term perinatal morbidity and long-term neurological outcome. The risks of caesarean section for the mother in the current and subsequent pregnancies must also be taken into account. OBJECTIVES: To determine the short- and long-term effects on mothers and their babies, of planned caesarean section for twin pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (18 November 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing a policy of caesarean section with planned vaginal birth for women with twin pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality and extracted data. Data were checked for accuracy. For important outcomes the quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included two trials comparing planned caesarean section versus planned vaginal birth for twin pregnancies.Most of the data included in the review were from a multicentre trial where 2804 women were randomised in 106 centres in 25 countries. All centres had facilities to perform emergency caesarean section and had anaesthetic, obstetrical, and nursing staff available in the hospital at the time of planned vaginal delivery. In the second trial carried out in Israel, 60 women were randomised. We judged the risk of bias to be low for all categories except performance (high) and outcome assessment bias (unclear).There was no clear evidence of differences between women randomised to planned caesarean section or planned vaginal birth for maternal death or serious morbidity (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.67 to 1.11; 2844 women; two studies; moderate quality evidence). There was no significant difference between groups for perinatal or neonatal death or serious neonatal morbidity (RR 1.15, 95% CI 0.80 to 1.67; data for 5565 babies, one study, moderate quality evidence). No studies reported childhood disability.For secondary outcomes there was no clear evidence of differences between groups for perinatal or neonatal mortality (RR 1.41, 95% CI 0.76 to 2.62; 5685 babies; two studies, moderate quality evidence), serious neonatal morbidity (RR 1.03, 95% CI 0.65 to 1.64; 5644 babies; two studies, moderate quality evidence) or any of the other neonatal outcomes reported.The number of women undergoing caesarean section was reported in both trials. Most women in the planned caesarean group had treatment as planned (90.9% underwent caesarean section), whereas in the planned vaginal birth group 42.9% had caesarean section for at least one twin. For maternal mortality; no events were reported in one trial and two deaths (one in each group) in the other. There were no significant differences between groups for serious maternal morbidity overall (RR 0.86, 95% CI 0.67 to 1.11; 2844 women; two studies) or for different types of short-term morbidity. There were no significant differences between groups for failure to breastfeed (RR 1.14, 95% CI 0.95 to 1.38; 2570 women, one study; moderate quality evidence) or the number of women with scores greater than 12 on the Edinbugh postnatal depression scale (RR 0.95, 95% CI 0.78 to 1.14; 2570 women, one study; moderate quality evidence). AUTHORS' CONCLUSIONS: Data mainly from one large, multicentre study found no clear evidence of benefit from planned caesarean section for term twin pregnancies with leading cephalic presentation. Data on long-term infant outcomes are awaited. Women should be informed of possible risks and benefits of labour and vaginal birth pertinent to their specific clinical presentation and the current and long-term effects of caesarean section for both mother and babies. There is insufficient evidence to support the routine use of planned caesarean section for term twin pregnancy with leading cephalic presentation, except in the context of further randomised trials. PMID- 26684390 TI - Balloon Dilatation for Removal of an Irretrievable Permanent Hemodialysis Catheter: The Safest Approach. AB - Long-term hemodialysis catheter dwell time in the central vein predisposes to fibrin sheath development, which subsequently causes catheter malfunction or occlusion. In very rare cases, the catheter can be overgrown with fibrin and rigidly connected with the vein or heart structures. This makes its removal almost impossible and dangerous because of the possibility of serious complications, namely vein and heart wall perforation, bleeding, or catheter abruption in deep tissues. We describe two cases in which standard retrieval of long-term catheters was not possible. Balloon dilatation of catheter lumens was successfully used to increase the catheter diameter with simultaneous tearing of the fibrin sheath surrounding it. This allowed the catheter to be set free safely. Based on this experience, we present recent literature and our point of view. PMID- 26684391 TI - The Emerging World of Small ORFs. AB - Small open reading frames (sORFs) are an often overlooked feature of plant genomes. Initially found in plant viral RNAs and considered an interesting curiosity, an increasing number of these sORFs have been shown to encode functional peptides or play a regulatory role. The recent discovery that many of these sORFs initiate with start codons other than AUG, together with the identification of functional small peptides encoded in supposedly noncoding primary miRNA transcripts (pri-miRs), has drastically increased the number of potentially functional sORFs within the genome. Here we review how advances in technology, notably ribosome profiling (RP) assays, are complementing bioinformatics and proteogenomic methods to provide powerful ways to identify these elusive features of plant genomes, and highlight the regulatory roles sORFs can play. PMID- 26684392 TI - Bloodstream infections in older patients. AB - Bloodstream infections (BSIs) are both common and fatal in older patients. We describe data from studies evaluating older patients hospitalized with BSIs. Most older patients with BSIs present "typically" with either fever or leukocytosis. The most common source of BSI in older patients is the urinary tract, and accordingly, Gram-negative organisms predominate. A significant part of these BSIs may thus be preventable by removal of unnecessary urinary catheters. Increased long term mortality is reported following BSIs in older patients, however, data on other long-term outcomes, including functional capacity, cognitive decline and others are lacking. Management of BSIs may include less invasive procedures due to the fragility of older patients. This approach may delay the diagnosis and treatment in some cases. Older patients are probably under-represented in clinical trials assessing treatment of bacteremia. Physicians treating older patients should consider the relevance of these studies' outcomes. PMID- 26684393 TI - High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial. AB - Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio >=0.010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0.001; inv(16), 0% vs. 100%, P < 0.001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P < 0.001; NUP98-NSD1, 100% vs. 0%, P < 0.001. The overall survival (OS) and event free survival (EFS) among PRDM16-overexpressing patients were significantly worse than in patients with low PRDM16 expression (3-year OS: 51% vs. 81%, P < 0.001, 3 year EFS: 32% vs. 64%, P < 0.001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3-internal tandem duplication-positive AML patients (3-year OS: high = 30% vs. low = 70%, P < 0.001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate-risk cytogenetic profiles and was independently associated with an adverse outcome. PMID- 26684394 TI - MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma. AB - Recent therapeutic advances have improved melanoma patients clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors. PMID- 26684395 TI - Dynamic Evolution of the Evaporating Liquid-Vapor Interface in Micropillar Arrays. AB - Capillary assisted passively pumped thermal management devices have gained importance due to their simple design and reduction in energy consumption. The performance of these devices is strongly dependent on the shape of the curved interface between the liquid and vapor phases. We developed a transient laser interferometry technique to investigate the evolution of the shape of the liquid vapor interface in micropillar arrays during evaporation heat transfer. Controlled cylindrical micropillar arrays were fabricated on the front side of a silicon wafer, while thin-film heaters were deposited on the reverse side to emulate a heat source. The shape of the meniscus was determined using the fringe patterns resulting from interference of a monochromatic beam incident on the thin liquid layer. We studied the evolution of the shape of the meniscus on these surfaces under various operating conditions including varying the micropillar geometry and the applied heating power. By monitoring the transient behavior of the evaporating liquid-vapor interface, we accurately measured the absolute location and shape of the meniscus and calculated the contact angle and the maximum capillary pressure. We demonstrated that the receding contact angle which determines the capillary pumping limit is independent of the microstructure geometry and the rate of evaporation (i.e., the applied heating power). The results of this study provide fundamental insights into the dynamic behavior of the liquid-vapor interface in wick structures during phase-change heat transfer. PMID- 26684397 TI - Minimum graft size calculated from preoperative recipient status in living donor liver transplantation. AB - Small-for-size graft syndrome is an inevitable complication in living donor liver transplantation (LDLT). We hypothesized that graft weight (GW) measured after graft procurement is one of the variables predicting postoperative graft function. A total of 138 consecutive recipients of adult-to-adult LDLT between March 1999 and October 2014 were included in this study. We investigated the factors associated with small-for-size-associated graft loss (SAGL) to determine the GW required for each patient. Both preoperatively assessed and postoperatively obtained risk factors for SAGL were analyzed in univariate and multivariate logistic regression analysis. Twelve (8.8%) of the transplant recipients had SAGL. In multivariate logistic regression analyses using preoperatively assessed variables, the preoperative Model for End-Stage Liver Disease (MELD) score (P < 0.001) and actual GW/recipient standard liver volume (SLV) ratio (P = 0.008) were independent predictors of SAGL. The recommended graft volume by preoperative computed tomography volumetry was calculated as SLV * (1.616 * MELD + 0.344)/100/0.85 (mL) [MELD >= 18.2], or SLV * 0.35 (mL) [MELD < 18.2]. The required allograft volume in LDLT can be determined by the preoperative MELD score of the recipient, and patients with higher MELD scores require larger grafts or deceased donor whole liver transplant to avoid SAGL. Liver Transplantation 22 599-606 2016 AASLD. PMID- 26684396 TI - Salivary Cortisol Profiles of Children with Hearing Loss. AB - OBJECTIVES: It has long been speculated that effortful listening places children with hearing loss at risk for fatigue. School-age children with hearing loss experiencing cumulative stress and listening fatigue on a daily basis might undergo dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in elevated or flattened cortisol profiles. The purpose of this study was to examine whether school-age children with hearing loss show different diurnal salivary cortisol patterns than children with normal hearing. DESIGN: Participants included 32 children with mild to moderate hearing loss (14 males; 18 females) and 28 children with normal hearing (19 males; 9 females) ranging in age from 6 to 12 years. Saliva samples were obtained six times per day on two separate school days. Cortisol levels were measured by mass spectrometric detection after liquid-liquid extraction. Salivary cortisol levels between children with hearing loss and children with no hearing loss over the course of the day were examined with hierarchical linear modeling using mixed model statistical analysis. Between-group comparisons were also computed for the area under the curve, an analytical approach for calculating overall cortisol secretion throughout the day. RESULTS: Significant differences in the cortisol awakening response (CAR) were observed between children with hearing loss and children with normal hearing; however, no differences were observed between the two groups subsequent to the cortisol awakening response (60-min postawakening, 10:00 A.M., 2:00 P.M., and 8:00 P.M.). Compared with children with normal hearing, children with hearing loss displayed elevated cortisol levels at awakening and a reduced growth in cortisol secretion from awakening to 30-min postawakening. No significant differences in overall cortisol secretion throughout the day were found between groups (area under the curve). Finally, cortisol levels increased with increasing age for children with hearing loss but not for children with normal hearing. CONCLUSIONS: Results of this preliminary study indicate a possible dysregulation in HPA axis activity in children with hearing loss characterized by elevated salivary cortisol levels at awakening and a diminished increase in cortisol from awakening to 30-min postawakening. The pattern of elevated cortisol levels at awakening is consistent with some studies on adults with burnout, a condition characterized by fatigue, loss of energy, and poor coping skills. These findings support the idea that children with hearing loss may experience increased vigilance and need to mobilize energy promptly in preparation for the new day. PMID- 26684398 TI - A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats. AB - The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague-Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-alpha aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS. PMID- 26684399 TI - Towards Ubiquitous Health with Convergence. PMID- 26684400 TI - Potential therapeutic mechanism of extremely low-frequency high-voltage electric fields in cells. AB - The aim of this survey was to provide background theory based on previous research to elucidate the potential pathway by which medical devices using extremely low-frequency high-voltage electric fields (ELF-HVEF) exert therapeutic effects on the human body, and to increase understanding of the AC high-voltage electrotherapeutic apparatus for consumers and suppliers of the relevant devices. Our review revealed that an ELF field as weak as 1-10 MU V/m can induce diverse alterations of membrane proteins such as transporters and channel proteins, including changes in Ca + + binding to a specific site of the cell surface, changes in ion (e.g., Ca + + ) influx or efflux, and alterations in the ligand receptor interaction. These alterations then induce cytoplasmic responses within cells (Ca + + , cAMP, kinases, etc.) that can have impacts on cell growth, differentiation, and other functional properties by promoting the synthesis of macromolecules. Moreover, increased cytoplasmic Ca + + involves calmodulin dependent signaling and consequent Ca + + /calmodulin-dependent stimulation of nitric oxide synthesis. This event in turn induces the nitric oxide-cGMP-protein kinase G pathway, which may be an essential factor in the observed physiological and therapeutic responses. PMID- 26684401 TI - Exposure dose reduction during lateral spine test with water filter. AB - To minimize exposure dose during lateral spine X-Ray testing and obtain optimal image for diagnosis a water filter was made to measure and evaluate dose distribution. When applying the water filter, as thickness increased exposure dose decreased. When applying 2 cm of water filter, clarity of contrast and boundary was found to be 4.5 +/- 0.5 and resolution was found to be 2.00 +/- 0.5 Lp/mm which was almost identical image quality compared to not applying water filter which showed clarity of contrast and boundary of 5.0 +/- 0.0, and resolution of 2.50 +/- 0.0 Lp/mm, while reducing exposure dose by 55%. This result is expected to have many uses as important basic data to predict exposure dose of patients and to minimize medical exposure dose through applying water filters during lateral spine X-Ray testing. PMID- 26684402 TI - Development of a death education curriculum model for the general public using DACUM method. AB - In order to analyze tasks of the death education curriculum for the public, DACUM method was used. A committee for DACUM was gathered and a survey was conducted on professors of health care, humanities and social sciences for an interdisciplinary study. In the survey used to verify the model for death education for the public, a compilation based on difficulty and importance factor shows that the 27 tasks including the psychological changes in terminally ill or suicidal patients, healing of stress, acceptance and understanding of death and suicide prevention were identified as needing to be included in the curriculum. The data thus concluded will have to be reviewed when they are applied to actual education to revise the education program to make it more appropriate. PMID- 26684403 TI - A study on the relationship between the protein supplements intake satisfaction level and repurchase intention: Verification of mediation effects of word-of mouth intention. AB - The purpose of this study is to examine the relationship between the protein supplements intake satisfaction level and repurchase intention of university students majoring in physical education and verify the mediation effects of word of-mouth intention. To achieve the purpose of this study, 700 university students majoring in physical education from 10 universities in Korea were selected from October 2013 to December 2013 as the target of this study through the cluster random sampling and data of 228 university students who had experience in the intake of protein supplements among them was analyzed. The composite reliability of each factor was in between 0.869 and 0.958, and the convergent validity and discriminant validity were verified. SPSS 18.0 and Amos 22.0 were utilized as data processing methods and the verification of significance on the medication effects and indirect effects of word-of-mouth intention was carried out using the frequency analysis, correlation analysis, CFA, SEM, and Amos bootstrapping. The result is as follows. The protein supplements intake satisfaction level had a positive effect on the word-of-mouth intention and the word-of-mouth intention had a positive effect on the repurchase intention. Also, it was shown that the word-of-mouth intention played a full mediation role between the intake satisfaction level and the repurchase intention. PMID- 26684404 TI - Effect of burdock extracts upon inflammatory mediator production. AB - We investigated the burdock extract on the inhibitions of NO generation, COX-2 expression, and the generations of IL-6 and TNF-alpha , to find out its anti inflammatory effect in this study. After the treatment of the burdock extract in the cells, we measured the amount of NO generated in the inflammatory cells developed by LPS and UVB, and confirmed the developments of inflammatory mediators by RT-PCR. Upon the results on the NO generation after the development of inflammation by LPS in Raw 264.7 cell, we found approximately 50% of inhibitory effect at 200 MUg/ml concentrations of the burdock extract. It was confirmed that the expression levels of TNF-alpha, COX-2, and IL-6 were declined to the levels of control by LPS and UVB stimulated inflammation in HaCat cell. This means the anti-inflammatory effect of the burdock extract. PMID- 26684405 TI - Neotropical primate communities: Effects of disturbance, resource production and forest type heterogeneity. AB - Undisturbed primate communities in the Neotropics are bottom-up structured as their biomass and species richness can be predicted from fruit production. However, the effects of fruit scarcity and the availability of forest types have not been fully analyzed, and seasonality is expected to differently affect small and large monkeys. The first aim of this study was to examine the effect of contrasting forest types within a location on the temporal variation in fruit production. The second was to assess the relative roles of disturbance, climate, patterns of fruit and leaf production, and plant composition on determining Neotropical primate communities. I compiled population density data for diurnal primate species from 154 sites to calculate species richness and assemblage biomass. Fruit abundance in the study sites was estimated from fruit trap data and phenology transects, and fruit variability was calculated as the monthly coefficient of variation (CV) and the length of the fruit scarcity period (LFSP). The results indicate that fruit production in floodplain forests is generally more variable than in terra firme forests, and this variation decreases in habitats with mixed forest types. Endozoochorous fruit production (based on fruit traps) and litter productivity were good predictors of the biomass of Neotropical primates (R2 = 0.83 and R2 = 0.59, respectively), but neither CV nor LFSP were good predictors. The biomass of large primates was independent of rainfall variation, but the biomass of small and medium sized monkeys was negatively correlated with temporal rainfall variability. Varzea forests tended to show higher biomass than those from terra firme and igapo. These results suggest that the production of fleshy fruits is the best predictor of the structure of primate assemblages in the Neotropics, but the effect of leaf quality and productivity remains to be investigated. Am. J. Primatol. 78:391-401, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26684407 TI - Synthetic High-Density Lipoprotein-Like Nanocarrier Improved Cellular Transport of Lysosomal Cholesterol in Human Sterol Carrier Protein-Deficient Fibroblasts. AB - Sterol carrier protein-2 (SCP-2), which is not found in tissues of people with Zellweger syndrome, facilitates the movement of cholesterol within cells, resulting in abnormal accumulation of cholesterol in SCP-2-deficient cells. This study investigated whether synthetic high-density lipoprotein-like nanocarrier (sHDL-NC) improves the cellular transport of lysosomal cholesterol to plasma membrane in SCP-2-deficient fibroblasts. Human SCP-2-deficient fibroblasts were incubated with [(3)H-cholesterol]LDL as a source of cholesterol and sHDL-NC. The cells were fractionated by centrifugation permit tracking of [(3)H]-cholesterol from lysosome into plasma membrane. Furthermore, cellular content of cholesteryl ester as a storage form and mRNA expression of low-density lipoprotein (LDL) receptor were measured to support the cholesterol transport to plasma membrane. Incubation with sHDL-NC for 8 h significantly increased uptake of [(3)H] cholesterol to lysosome by 53% and further enhanced the transport of [(3)H] cholesterol to plasma membrane by 32%. Treatment with sHDL-NC significantly reduced cellular content of cholesteryl ester and increased mRNA expression of LDL receptor (LDL-R). In conclusion, sHDL-NC enables increased transport of lysosomal cholesterol to plasma membrane. In addition, these data were indirectly supported by decreased cellular content of cholesteryl ester and increased gene expression of LDL-R. Therefore, sHDL-NC may be a useful vehicle for transporting cholesterol, which may help to prevent accumulation of cholesterol in SCP-2 deficient fibroblasts. PMID- 26684406 TI - Intravenous isotonic fluids induced a positive trend in natraemia in children admitted to a general paediatric ward. AB - AIM: Using hypotonic intravenous solutions for baseline fluid needs in paediatric patients on a nil by mouth diet may cause serious complications, including hyponatraemia, cerebral oedema and even death. We analysed the evolution of natraemia and explored any adverse effects on children treated with intravenous isotonic fluids. METHODS: This was a prospective study of 50 patients consecutively admitted to a general paediatric ward who were treated with isotonic intravenous fluids and on a nil by mouth diet. RESULTS: The most prevalent diagnosis was acute gastroenteritis (64%). Hyponatraemia, defined as sodium in plasma of <135 mEq/L, affected 22% of the subjects, but none displayed this during the first postadmission analysis at a median of eight hours. Sodium levels changed by an average of +0.64 mEq/L/hour. The subgroup analysis (0.91 versus 0.56 mEq/L/hour, p = 0.02) and multiple linear regression (R(2) = 0.756) showed a greater increase in sodium when patients had hyponatraemia on admission. Iatrogenic hyponatraemia was not detected, but two patients showed mild hypernatraemia and 35% developed clinically insignificant hyperchloraemia. CONCLUSION: Using intravenous isotonic fluids induced a positive trend in natraemia on a general paediatric ward, particularly if patients were hyponatraemic when admitted, and did not induce clinically relevant adverse effects. PMID- 26684408 TI - Impediments to Comparative Clinical Trials With Proton Therapy. PMID- 26684409 TI - What Are Medical Students in the United States Learning About Radiation Oncology? Results of a Multi-Institutional Survey. AB - PURPOSE: The purposes of this study were to assess the exposure that medical students (MSs) have to radiation oncology (RO) during the course of their medical school career, as evidenced by 2 time points in current medical training (ie, first vs fourth year; MS1s and MS4s, respectively) and to assess the knowledge of MS1s, MS4s, and primary care physicians (PCPs) about the appropriateness of RT in cancer management in comparison with RO attendings. METHODS: We developed and beta tested an electronic survey divided into 3 parts: RO job descriptions, appropriateness of RT, and toxicities of RT. The surveys were distributed to 7 medical schools in the United States. A concordance of >90% (either yes or no) among RO attendings in an answer was necessary to determine the correct answer and to compare with other subgroups using a chi(2) test (P<.05 was significant). RESULTS: The overall response rate for ROs, MS1s, MS4s, and PCPs was 26%; n (22 + 315 + 404 + 43)/3004. RT misconceptions decreased with increasing level of training. More than 1 of 10 MSs did not believe that RT alone could cure cancer. Emergent oncologic conditions for RT (eg, spinal cord compression, superior vena cava syndrome) could not be identified by >1 of 5 respondents. Multiple nontoxicities of RT (eg, emitting low-level radiation from the treatment site) were incorrectly identified as toxicities by >1 of 5 respondents. MS4s/PCPs with an RO rotation in medical school had improved scores in all prompts. CONCLUSIONS: Although MS knowledge of general RT principles improves from the first to the fourth year, a large knowledge gap still exists between MSs, current PCPs, and ROs. Some basic misconceptions of RT persist among a minority of MSs and PCPs. We recommend implementing formal education in RO fundamentals during the core curriculum of medical school. PMID- 26684410 TI - The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine. AB - PURPOSE: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. METHODS AND MATERIALS: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. RESULTS: By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. CONCLUSIONS: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy. PMID- 26684411 TI - Mechanism of Hydrotropic Action of Hydrotrope Sodium Cumene Sulfonate on the Solubility of Di-t-Butyl-Methane: A Molecular Dynamics Simulation Study. AB - Hydrotropes are special class of amphiphilic molecules that have an ability to solubilize the insoluble or sparingly soluble molecules in water. To find out the mechanism of hydrotropic action of hydrotropes on hydrophobic molecules, we have carried out classical molecular dynamics simulation of hydrophobic solute di-t butyl-methane (DTBM) and hydrotrope sodium cumene sulfonate (SCS) in water with a regime of SCS concentrations. Our study demonstrates that, above the minimum hydrotrope concentration (MHC), the self-aggregation of SCS starts, and it creates a micellar-like environment in which the hydrophobic tail part of SCS points inward while its hydrophilic sulfonate group points outward to make favorable contact with water molecules. The formation of the hydrophobic core of SCS cluster creates a hydrophobic environment where the hydrophobic DTBM molecules are encapsulated. Interestingly, the determination of average water-SCS hydrogen bonds further suggests that the aggregate formation of SCS molecules has a negligible influence on it. Moreover, the calculations of Flory-Huggins interaction parameters also reveal favorable interactions between hydrotrope SCS and solute DTBM molecules. The implications of these findings on the mechanism of hydrotrope assisted enhanced solubility of hydrophobic molecules are discussed. PMID- 26684413 TI - Coupling of Phosphate-Imprinted Mesoporous Silica Nanoparticles-Based Selective Enrichment with Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry for Highly Efficient Analysis of Protein Phosphorylation. AB - Protein phosphorylation is a major post-translational modification and represents a ubiquitous mechanism for the cellular signaling of many different biological processes. Selective enrichment of phosphopeptides from the complex biological samples is a key step for the mass spectrometric (MS) analysis of protein phosphorylation. Herein, we present phosphate-imprinted mesoporous silica nanoparticles (MSNs) as an ideal sorbent for selective enrichment of phosphopeptides and an off-line combination with matrix-asisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for highly efficient analysis of protein phosphorylation. The phosphate-imprinted MSNs were prepared according to a newly reported strategy called dual-template docking oriented molecular imprinting (DTD-OMI). The prepared molecularly imprinted mesoporous material exhibited several significant merits, such as excellent selectivity toward phosphopeptides, tolerance to interference, fast binding equilibrium, and large binding capacity, which made the molecularly imprinted mesoporous material an ideal sorbent for selective enrichment of phosphopeptides. Using beta-casein as a representative phosphoprotein, highly efficient phosphorylation analysis by the off-line platform was verified. Phosphorylation analysis of a nonfat milk sample was also well demonstrated. Because of their highly desirable properties, the phosphate-imprinted MSNs could find more applications in the analysis of protein phosphorylation. PMID- 26684412 TI - Design and fabrication of a 3D-structured gold film with nanopores for local electric field enhancement in the pore. AB - Three-dimensionally structured gold membrane films with nanopores of defined, periodic geometries are designed and fabricated to provide the spatially localised enhancement of electric fields by manipulation of the plasmons inside nanopores. Square nanopores of different size and orientation relative to the pyramid are considered for films in aqueous and air environments, which allow for control of the position of electric fields within the structure. Designs suitable for use with 780 nm light were created. Here, periodic pyramidal cavities produced by potassium hydroxide etching to the {111} planes of (100) silicon substrates are used as templates for creating a periodic, pyramidal structured, free-standing thin gold film. Consistent with the findings from the theoretical studies, a nano-sized hole of 50 nm square was milled through the gold film at a specific location in the cavity to provide electric field control which can subsequently used for enhancement of fluorescence or Raman scattering of molecules in the nanopore. PMID- 26684414 TI - miR expression profiling at diagnosis predicts relapse in pediatric precursor B cell acute lymphoblastic leukemia. AB - Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high-throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR-151-5p, and miR-451, and high expression of miR-1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5-fold increased risk of relapse (P = 0.041) in PCR-MRD non-high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5-fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non-BFM treated precursor B-cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR-151-5p, miR-451, and miR-1290 as a novel biomarker for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients. PMID- 26684415 TI - Lexical selection differences between monolingual and bilingual listeners. AB - Three studies are reported investigating how monolinguals and bilinguals resolve within-language competition when listening to isolated words. Participants saw two pictures that were semantically-related, phonologically-related, or unrelated and heard a word naming one of them while event-related potentials were recorded. In Studies 1 and 2, the pictures and auditory cue were presented simultaneously and the related conditions produced interference for both groups. Monolinguals showed reduced N400s to the semantically-related pairs but there was no modulation in this component by bilinguals. Study 3 inserted an interval between picture and word onset. For picture onset, both groups exhibited reduced N400s to semantically-related pictures; for word onset, both groups showed larger N400s to phonologically-related pictures. Overall, bilinguals showed less integration of related items in simultaneous (but not sequential) presentation, presumably because of interference from the activated non-English language. Thus, simple lexical selection for bilinguals includes more conflict than it does for monolinguals. PMID- 26684416 TI - Optimization of the Energy Level Alignment between the Photoactive Layer and the Cathode Contact Utilizing Solution-Processed Hafnium Acetylacetonate as Buffer Layer for Efficient Polymer Solar Cells. AB - The insertion of an appropriate interfacial buffer layer between the photoactive layer and the contact electrodes makes a great impact on the performance of polymer solar cells (PSCs). Ideal interfacial buffer layers could minimize the interfacial traps and the interfacial barriers caused by the incompatibility between the photoactive layer and the electrodes. In this work, we utilized solution-processed hafnium(IV) acetylacetonate (Hf(acac)4) as an effective cathode buffer layer (CBL) in PSCs to optimize the energy level alignment between the photoactive layer and the cathode contact, with the short-circuit current density (Jsc), open-circuit voltage (Voc), and fill factor (FF) all simultaneously improved with Hf(acac)4 CBL, leading to enhanced power conversion efficiencies (PCEs). Ultraviolet photoemission spectroscopy (UPS) and scanning Kelvin probe microscopy (SKPM) were performed to confirm that the interfacial dipoles were formed with the same orientation direction as the built-in potential between the photoactive layer and Hf(acac)4 CBL, benefiting the exciton separation and electron transport/extraction. In addition, the optical characteristics and surface morphology of the Hf(acac)4 CBL were also investigated. PMID- 26684417 TI - Financial Contribution of Residents When Billing as "Junior Associates" in the "Surgical Firm". AB - OBJECTIVE: There is an increasing number of proposals to change the way Graduate Medical Education is funded. This study attempts to estimate the potential financial contribution of surgical residents using an alternative funding mechanism similar to that used by law firms, which would allow surgery departments to bill for resident activity as "junior associates." METHODS: Following 24 residents over a period of 12 weeks, we were able to estimate the annual revenue that they generated from operating room procedures, independent consultations, patient management, and minor procedures using Medicare reimbursement rates. The appropriate first assistant modifier was used to calculate the operating room procedure fees, but full price was used to calculate the revenue for minor procedures, patient management, and consultations done independently. We adjusted for vacation time and academic activities. RESULTS: Including postgraduate year 1 residents, the estimated yearly revenue generated per resident in first assistant operative services was $33,305.67. For minor procedures, patient management, and independent consultations, the estimated yearly revenue per resident was $37,350.66. The total estimated financial contribution per resident per year was $70,656.33. Excluding postgraduate year 1 residents, as most states require completion of the intern year before full licensure, the estimated yearly revenue generated per resident in first assistant operative services was $38,914.56. For minor procedures, patient management, and independent consultations, the estimated yearly revenue per resident was $55,957.33. The total estimated financial contribution per resident per year was $94,871.89. CONCLUSIONS: Residents provide a significant service to hospitals. If resident activity was compensated at the level of supervised "junior associates" of a surgery department, more than 75% of the direct educational costs of training could be offset. Furthermore, we believe this value is underestimated. Given the foreseeable changes in Graduate Medical Education funding, it is imperative that alternative approaches for funding be explored. PMID- 26684419 TI - Cinema and Neuroscience: Development and Application of Cinematography in the Field of the Neurosciences. PMID- 26684418 TI - Design and Implementation of a Competency-Based Transfusion Medicine Training Program in Canada. AB - Transfusion medicine training in Canada is currently undergoing a transformation from a time- and process-based curriculum to a competency-based medical education framework. Transfusion medicine is the first accredited postgraduate medical education training program in Canada to adopt a purely competency-based curriculum. It is serving as an example for a number of other postgraduate medical training programs undergoing a similar transition. The purpose of this review is to highlight the elements of competency-based medical education, describe its application to transfusion medicine training, and report on the development and implementation of the new transfusion medicine curriculum in Canada. PMID- 26684420 TI - Capturing Motion and Depth Before Cinematography. AB - Visual representations of biological states have traditionally faced two problems: they lacked motion and depth. Attempts were made to supply these wants over many centuries, but the major advances were made in the early-nineteenth century. Motion was synthesized by sequences of slightly different images presented in rapid succession and depth was added by presenting slightly different images to each eye. Apparent motion and depth were combined some years later, but they tended to be applied separately. The major figures in this early period were Wheatstone, Plateau, Horner, Duboscq, Claudet, and Purkinje. Others later in the century, like Marey and Muybridge, were stimulated to extend the uses to which apparent motion and photography could be applied to examining body movements. These developments occurred before the birth of cinematography, and significant insights were derived from attempts to combine motion and depth. PMID- 26684421 TI - The Dercum-Muybridge Collaboration and the Study of Pathologic Gaits Using Sequential Photography. AB - In the late 1870s and 1880s, prior to the development of movie cameras or projectors, English-American photographer Eadweard Muybridge (1830-1904) photographed sequential images of people and animals in motion, using arrays of sequentially triggered single-image cameras. In 1885, Philadelphia neurologist Francis Dercum (1856-1931) collaborated with Muybridge at the University of Pennsylvania to photograph sequential images of patients with various neurological disorders involving abnormal movements, and particularly various gait disorders, including both the sensory ataxic gait of tabes dorsalis and various spastic gaits. Dercum used tracings of sequential photographic images to plot trajectories of limbs as a way to characterize and distinguish pathologic gaits. The Dercum-Muybridge collaboration produced the first motion-picture sequences of neurological gait disorders ever filmed. These sequences and the trajectory-based studies that derived from them were a milestone in studies of pathologic gaits. PMID- 26684422 TI - Professor Camillo Negro's Neuropathological Films. AB - Camillo Negro, Professor in Neurology at the University of Torino, was a pioneer of scientific film. From 1906 to 1908, with the help of his assistant Giuseppe Roasenda and in collaboration with Roberto Omegna, one of the most experienced cinematographers in Italy, he filmed some of his patients for scientific and educational purposes. During the war years, he continued his scientific film project at the Military Hospital in Torino, filming shell-shocked soldiers. In autumn 2011, the Museo Nazionale del Cinema, in partnership with the Faculty of Neurosciences of the University of Torino, presented a new critical edition of the neuropathological films directed by Negro. The Museum's collection also includes 16 mm footage probably filmed in 1930 by Doctor Fedele Negro, Camillo's son. One of these films is devoted to celebrating the effects of the so-called "Bulgarian cure" on Parkinson's disease. PMID- 26684424 TI - Arthur Simons (1877-1942) and Tonic Neck Reflexes With Hemiplegic "Mitbewegungen" (Associated Reactions): Cinematography From 1916-1919. AB - Tonic neck reflexes were investigated by Rudolf Magnus and Adriaan de Kleijn in animals and men in 1912 and eventually by Arthur Simons, a neurologist in Berlin and coworker of Hermann Oppenheim. Simons studied these reflexes in hemiplegic patients, who were mainly victims of World War I. This work became his most important contribution and remained unsurpassed for many years. The film (Filmarchiv, Bundesarchiv [Film Archive, National Archive] Berlin) with Simons as an examiner shows 11 war casualties with brain lesions that occurred between 1916 and 1919. The injuries reveal asymmetric neck reflexes with "Mitbewegungen," that is, flexion or extension on the hemiplegic side. Mitbewegungen is identical with Francis Walshe's "associated reactions" caused by neck rotation and/or by cocontraction of the nonaffected extremities, for example, by closing of the fist (Walshe). The knowledge of the neck reflexes is important in acute neurology and in rehabilitation therapy of hemiplegics for antispastic positions. Simons' investigations were conducted in the early era of increasing use of cinematography in medical studies. The film had been nearly forgotten until its rediscovery in 2010. PMID- 26684423 TI - Vincenzo Neri and His Legacy in Paris and Bologna. AB - Italian neurologist Vincenzo Neri was able to discover cinematography at the beginning of his career, when in 1908 he went to Paris to learn and improve his clinical background by following neurological cases at La Pitie with Joseph Babinski, who became his teacher and friend. While in Paris, Neri photographed and filmed several patients of famous neurologists, such as Babinski and Pierre Marie. His stills were published in several important French neurological journals and medical texts. He also collaborated with Georges Mendel, who helped Doyen film the first known surgical operation in the history of cinema. In 1910, when he came back to Bologna, he continued in his clinical activities and, for 50 years, slowly developed a huge archive of films, images, and prints of neurological, psychiatric, and orthopedic cases. This archive was extremely helpful to Neri, who especially needed to analyze neurological disorders and to differentiate them from functional conditions in order to understand clinical signs, rules, and mechanisms. PMID- 26684425 TI - Jean Comandon Neuroscientist. AB - The microbiologist Jean Comandon is famous for his studies on the movement of the syphilis bacteria as differentiated in various forms by ultramicroscope. He was also a pioneer on the technical application of the microcinematography in laboratory research. His collaboration with clinicians and surgeons in the study of various pathological disorders is little known. From 1918 to the 1920s, he collaborated with such neurologists as Andre Thomas, Jean Athanase Sicard, and others in the study of various neurological disorders by using cinematography as a scientific tool for understanding the clinical and pathological mechanisms of diseases. These collaborations allowed him to be involved in the beginnings of the French cinematography industry, especially with Charles Pathe who established a small film studio laboratory in Vincennes where a multidisciplinary group improved the application of cinematography in clinical medical practice. PMID- 26684426 TI - Neurocinematography in Pre-World War II Netherlands: The Magnus-Rademaker Collection. AB - Historical films made by neuroscientists have shown up in several countries during past years. Although originally supposed to have been lost, we recently found a collection of films produced between 1909 and 1940 by Rudolf Magnus (1873 1927), professor of pharmacology (Utrecht) and his student Gysbertus Rademaker (1887-1957), professor of physiology (1928, succeeding Willem Einthoven) and neurology (1945, both in Leiden). Both collections deal with the physiology of body posture by the equilibrium of reflex musculature contractions for which experimental studies were done with animals (labyrinthectomies, cerebellectomies, and brainstem sections) and observations on patients. The films demonstrate the results of these studies. Moreover, there are films with babies showing tonic neck reflexes and moving images capturing adults with cerebellar symptoms following cerebellectomies for tumors and several other conditions. Magnus' studies resulted in his well-known Korperstellung (1924, "Body Posture") and Rademaker's research in his Das Stehen (1931, "Standing"). The films probably had an educative and scientific purpose. Magnus demonstrated his films at congresses, including the Eighth International Congress of Physiologists (Vienna, 1910) and Rademaker screened his moving images at meetings of the Amsterdam Neurologists Society (at several occasions as reflected in the Winkler-Monakow correspondence and the Nederlands Tijdschrift voor Geneeskunde). Next to these purposes, the films were used to analyze movement and a series of images from the films were published in articles and books. The films are important historical sources that provide a portrait of the pre-World War II era in neuroscience, partly answering questions on how physicians dealt with patients and researchers with their laboratory animals. Moreover, the films confirm that cinematography was an important scientific tool in neuroscience research. PMID- 26684427 TI - The Magnus-Rademaker Scientific Film Collection: Ethical Issues on Animal Experimentation (1908-1940). AB - The Magnus-Rademaker scientific film collection (1908-1940) deals with the physiology of body posture by the equilibrium of reflex musculature contractions for which experimental studies were carried out with animals (e.g., labyrinthectomies, cerebellectomies, and brain stem sections) as well as observations done on patients. The films were made for demonstrations at congresses as well as educational objectives and film stills were published in their books. The purpose of the present study is to position these films and their makers within the contemporary discourse on ethical issues and animal rights in the Netherlands and the earlier international debates. Following an introduction on animal rights and antivivisection movements, we describe what Magnus and Rademaker thought about these issues. Their publications did not provide much information in this respect, probably reflecting their adherence to implicit ethical codes that did not need explicit mentioning in publications. Newspaper articles, however, revealed interesting information. Unnecessary suffering of an animal never found mercy in Magnus' opinion. The use of cinematography was expanded to the reduction of animal experimentation in student education, at least in the case of Rademaker, who in the 1930s was involved in a governmental committee for the regulation of vivisection and cooperated with the antivivisection movement. This resulted not only in a propaganda film for the movement but also in films that demonstrate physiological experiments for students with the purpose to avert repetition and to improve the teaching of experiments. We were able to identify the pertinent films in the Magnus-Rademaker film collection. The production of vivisection films with this purpose appears to have been common, as is shown in news messages in European medical journals of the period. PMID- 26684428 TI - Two Authors Reply. PMID- 26684429 TI - Re: "A Vaccine Study Design Selection Framework for the Postlicensure Rapid Immunization Safety Monitoring Program". PMID- 26684430 TI - The poro-elastic behaviour of the intervertebral disc: A new perspective on diurnal fluid flow. AB - Diurnal disc height changes, due to fluid in- and outflow, are in equilibrium while daytime spinal loading is twice as long as night time rest. A direction dependent permeability of the endplates, favouring inflow over outflow, reportedly explains this; however, fluid flow through the annulus fibrosus should be considered. This study investigates the fluid flow of entire intervertebral discs. Caprine discs were preloaded in saline for 24h under four levels of static load. Under sustained load, we modulated the disc's swelling pressure by exchanging saline for demineralised water (inflow) and back to saline (outflow), both for 24h. We measured disc height creep and used stretched exponential models to determine time-constants. During inflow disc height increased in relation to applied load, and during outflow disc height decreased to preload levels. When comparing in- and outflow phases, there was no difference in creep, and time constants were similar indicating no direction-dependent resistance to fluid flow in the entire intervertebral disc. Results provoked a new hypothesis for diurnal fluid flow: in vitro time-constants for loading are shorter than for unloading and in vivo daytime loading is twice as long as night time unloading, i.e. in diurnal loading the intervertebral disc is closer to loading equilibrium than to unloading equilibrium. Per definition, fluid flow is slower close to equilibrium than far from equilibrium; therefore, as diurnal loading occurs closer to loading equilibrium, fluid inflow during night time unloading can balance fluid outflow during daytime loading, despite a longer time-constant. PMID- 26684431 TI - Thoracolumbar spine model with articulated ribcage for the prediction of dynamic spinal loading. AB - Musculoskeletal modeling offers an invaluable insight into the spine biomechanics. A better understanding of thoracic spine kinetics is essential for understanding disease processes and developing new prevention and treatment methods. Current models of the thoracic region are not designed for segmental load estimation, or do not include the complex construct of the ribcage, despite its potentially important role in load transmission. In this paper, we describe a numerical musculoskeletal model of the thoracolumbar spine with articulated ribcage, modeled as a system of individual vertebral segments, elastic elements and thoracic muscles, based on a previously established lumbar spine model and data from the literature. The inverse dynamics simulations of the model allow the prediction of spinal loading as well as costal joints kinetics and kinematics. The intradiscal pressure predicted by the model correlated well (R(2)=0.89) with reported intradiscal pressure measurements, providing a first validation of the model. The inclusion of the ribcage did not affect segmental force predictions when the thoracic spine did not perform motion. During thoracic motion tasks, the ribcage had an important influence on the predicted compressive forces and muscle activation patterns. The compressive forces were reduced by up to 32%, or distributed more evenly between thoracic vertebrae, when compared to the predictions of the model without ribcage, for mild thoracic flexion and hyperextension tasks, respectively. The presented musculoskeletal model provides a tool for investigating thoracic spine loading and load sharing between vertebral column and ribcage during dynamic activities. Further validation for specific applications is still necessary. PMID- 26684432 TI - Erythrocyte aggregation may promote uneven spatial distribution of NO/O2 in the downstream vessel of arteriolar bifurcations. AB - This study examined the effect of red blood cell (RBC) aggregation on nitric oxide (NO) and oxygen (O2) distributions in the downstream vessels of arteriolar bifurcations. Particular attention was paid to the inherent formation of asymmetric cell-free layer (CFL) widths in the downstream vessels and its consequential impact on the NO/O2 bioavailability after the bifurcations. A microscopic image-based two-dimensional transient model was used to predict the NO/O2 distribution by utilizing the in vivo CFL width data obtained under non-, normal- and hyper-aggregating conditions at the pseudoshear rate of 15.6+/-2.0s( 1). In vivo experimental result showed that the asymmetry of CFL widths was enhanced by the elevation in RBC aggregation level. The model demonstrated that NO bioavailability was regulated by the dynamic fluctuation of the local CFL widths, which is corollary to its modulation of wall shear stress. Accordingly, the uneven distribution of NO/O2 was prominent at opposite sides of the arterioles up to six vessel-diameter (6D) away from the bifurcating point, and this was further enhanced by increasing the levels of RBC aggregation. Our findings suggested that RBC aggregation potentially augments both the formation of asymmetric CFL widths and its influence on the uneven distribution of NO/O2 in the downstream flow of an arteriolar bifurcation. The extended heterogeneity of NO/O2 downstream (2D-6D) also implied its potential propagation throughout the entire arteriolar microvasculature. PMID- 26684433 TI - Investigation of In Vivo skin stiffness anisotropy in breast cancer related lymphoedema. AB - There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/-2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/-16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants. PMID- 26684434 TI - An experimental approach to a simplified model of human birth. AB - This study presents a simplified experimental model of labor for the study of fetal lie and amniotic fluid properties. It mimics a ventouse (vacuum extraction) delivery to study the effect of amniotic fluid properties on force transfer to a passive fetus. The simplified vacuum delivery consists of a solid ovate spheroid being pulled from a passive, flexible spherical elastic shell filled with fluid. We compare the force necessary to remove the ovate fetus in fluids of varying properties. Additionally, the fetal lie-angular deviation from maternal/fetal spinal alignment-is changed by 5 degrees intervals and the pullout force is measured. In both the concentric ovate experiments, the force to remove the fetus changes with the properties of the fluid occupying the space between the fetus and the uterus. Increasing the fluid viscosity by 35% decreases the maximum fetal removal force by up to 52.5%. Furthermore, while the force is dominated by the elastic force of the latex uterus, the properties of the amniotic fluid can significantly decrease the total removal force. This study demonstrates that the fluid components of a birth model can significantly alter the forces associated with fetus removal. This suggests that complete studies of human parturition should be designed to include both the material and fluid systems. PMID- 26684436 TI - Bicycling for transportation improves heart rate variability in young adults. AB - BACKGROUND: Physical activity has been considered an effective method to treat and prevent cardiovascular and metabolic disease. An important mechanism benefited by exercise training is the cardiovascular autonomic control, often impaired in cardiometabolic disease. Cycling used as a daily means of transport can be considered an interesting alternative to regular physical exercise practice. Therefore, this study intent to compare metabolic, hemodynamic and cardiovascular autonomic profiles of young adult men who were used to cycle for transportation (CT) with those considered insufficiently actives (IA). METHODS: Body composition, blood pressure, glucose, total cholesterol and triglycerides were evaluated at rest. Heart rate variability was analyzed in time and frequency domains. RESULTS: No differences were observed for body composition, blood pressure, glycemia nor lipids between groups. CT group presented resting bradycardia. Heart rate variability was increased in cyclists, as well as the parameters of parasympathetic modulation. Sympathetic modulation was reduced in CT group when compared to IA group. Additionally, positive correlations were observed between resting heart rate and RMSSD and heart rate variability, while heart rate variability was correlated with sympathovagal balance. CONCLUSIONS: Our results demonstrated that bicycling regularly used as a means of transport is able to improve cardiovascular autonomic modulation, thus reducing the risk of cardiovascular disease. PMID- 26684435 TI - Actinide(IV) Deposits on Bone: Potential Role of the Osteopontin-Thorium Complex. AB - In case of a nuclear event, contamination (broad or limited) of the population or of specific workers might occur. In such a senario, the fate of actinide contaminants may be of first concern, in particular with regard to human target organs like the skeleton. To improve our understanding of the toxicological processes that might take place, a mechanistic approach is necessary. For instance, ~50% of Pu(IV) is known from biokinetic data to accumulate in bone, but the underlining mechanisms are almost unknown. In this context, and to obtain a better description of the toxicological mechanisms associated with actinides(IV), we have undertaken the investigation, on a molecular scale, of the interaction of thorium(IV) with osteopontin (OPN) a hyperphosphorylated protein involved in bone turnover. Thorium is taken here as a simple model for actinide(IV) chemistry. In addition, we have selected a phosphorylated hexapeptide (His-pSer-Asp-Glu-pSer Asp-Glu-Val) that is representative of the peptidic sequence involved in the bone interaction. For both the protein and the biomimetic peptide, we have determined the local environment of Th(IV) within the bioactinidic complex, combining isothermal titration calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, theoretical calculations with density functional theory, and extended X-ray absorption fine structure spectroscopy at the Th LIII edge. The results demonstrate a predominance of interaction of metal with the phosphate groups and confirmed the previous physiological studies that have highlighted a high affinity of Th(IV) for the bone matrix. Data are further compared with those of the uranyl case, representing the actinyl(V) and actinyl(VI) species. Last, our approach shows the importance of developing simplified systems [Th(IV) peptide] that can serve as models for more biologically relevant systems. PMID- 26684437 TI - Functional training reduces body fat and improves functional fitness and cholesterol levels in postmenopausal women: a randomized clinical trial. AB - BACKGROUND: This randomized clinical trial with concealed allocations, and blinding of the assessors and the data analyst, was aimed at determining the effects of 16 weeks of functional training on the body composition, functional fitness and lipid profiles in postmenopausal women. METHODS: The study began with 64 subjects (N.=32 functional training and N.=32 control group) and ended with 50 subjects (N.=28 functional training and N.=22 control group). The exercise was conducted in circuit training format with 8 stations related to the development of muscular strength (using elastic bands for resistance) plus 3 stations focused on balance, coordination, and agility. The training session also incorporated an 18 to 30 minute walk. The control group did not participate in the exercise programs during the period of study. The participants were evaluated before and after the training period as regards their body composition (fat and lean mass), functional fitness, abdominal strength and blood chemistry variables. RESULTS: Significant reductions were observed in all body composition variables related to fat (FM= -3.4 and Android FM= -7.7%) (P<0.05). The functional fitness components had significant improvements in coordination (-33.3%), strength (66.5%), agility (-19.5%) and aerobic capacity (-7%), and significant improvement in abdominal strength (188.2%). We observed significant improvements in total cholesterol ( 4.4%) and HDL (-9.9%). CONCLUSIONS: The observed data lead us to conclude that functional training utilizing with elastic bands and unstable bases causes significantly improved in body composition, functional fitness and lipid profiles. PMID- 26684438 TI - The accuracy of musculoskeletal ultrasound examination for the exploration of meniscus injuries in athletes. AB - BACKGROUND: Meniscus injuries represent a frequently occurring pathology in athletes and require an optimum diagnosis protocol. This study aimed to evaluate the accuracy of ultrasound examination for the identification of meniscus injuries, in comparison with magnetic resonance imaging (MRI), using the arthroscopy as reference. METHODS: This prospective longitudinal comparative study included 45 athletes who were clinically examined by MRI and further, by arthroscopy, in a medical center dedicated to sport traumatology. RESULTS: The conventional ultrasound exploration of the knee allowed the identification of a diverse pathology, presenting a sensitivity of 88.8% for the diagnosis of medial meniscus injuries and 70.0% for the lateral meniscus. The specificity was 77.7% for the medial meniscus and 96.0% for the identification of lateral meniscus injuries. Using MRI, a sensitivity of 69.4% was obtained for the medial meniscus and 75.0% for the lateral meniscus, with a specificity of 76.6% for the pathology of medial meniscus and 80.0% for the lateral meniscus. Statistical analysis, based on the comparison of ROC curves, did not show any significant difference between the two applied diagnostic techniques (P=0.061 for the medial meniscus and P=0.534 for the lateral meniscus). CONCLUSIONS: The musculoskeletal ultrasound exploration of the knee joint, performed in a medical center with high addressability, by an experienced examiner, was able to identify the medial and lateral meniscus injuries with an accuracy comparable to that of MRI examination. PMID- 26684439 TI - Effects of detraining on neuromuscular performance in a selected group of elite women pole-vaulters: a case study. AB - AIM: to determine the effects of 28 days of inactivity on neuromuscular performance of elite women pole-vaulters. METHODS: Four athletes undertook measurements of rate of force development (RFD), unloaded and loaded vertical jump tests, drop jumps and a 45 m sprint test before and after a transition period of planned inactivity. RESULTS: The RFD and the ability to accelerate over very short distances (5 m) while sprinting improved after training cessation. Acceleration over longer distances (5-45 m) was impaired, while unloaded and loaded vertical jump tests suffered trivial to small changes. CONCLUSIONS: Therefore, we conclude that detraining periods of approximately one month or even longer may be implemented in elite pole-vaulters without significantly impairing performance. In addition, given that some neuromechanical capacities are enhanced after training reduction, our results can help coaches to implement tapering strategies in order to induce neuromuscular improvements and/or to achieve peak performance. PMID- 26684440 TI - Changes in Intracellular Water Following Hemodialysis Treatment Lead to Changes in Estimates of Lean Tissue Using Bioimpedance Spectroscopy. AB - BACKGROUND: Bioelectrical impedance (BIA) devices are being introduced into hemodialysis (HD) centers to aid determining normohydrated weight and also provide body composition assessment by estimating lean tissue mass index (LTMI) and fat mass index (FMI). BIA devices differ, with most using a 2-body compartmental model, which can be affected by hydration status, and as such for reliable measurements, these should be made postdialysis when patients are not overhydrated, which is inconvenient for both patients and staff. The development of BIA devices using a 3-compartmental body model, separately estimating normohydrated LTMI potentially, now offers the advantage of making reliable measurements of body composition prior to dialysis. MATERIALS AND METHODS: We measured body composition predialysis and postdialysis in 50 HD patients using a 3-body compartment model BIA device. RESULTS: Although there were no statistically significant differences for the whole cohort in LTMI and FMI (pre and post HD-13.5 +/- 4.2 vs 13.9 +/- 4.7 kg/m(2), and 10.5 +/- 5.5 vs 10.6 +/- 5.4 kg/m(2) respectively), the correlation (r(2)) between pre and post HD was only 0.27 and 0.37 kg/m(2) respectively, with a mean +/- SD bias on Bland-Altman analysis, -0.67 +/- 4.25 and 0.33 +/- 4.77 kg/m(2) respectively. Changes in intracellular water were associated with changes in LTMI (r(2) = 0.99, P < .001). Similarly, a fall in LTMI was associated with a corresponding increase in FMI (r(2) = -0.86, P < .001). CONCLUSION: In clinical practice, predialysis bioimpedance measurements are more convenient. However, for more reliable and reproducible assessments of nutrition status, we suggest that measurements of body composition should be made when patients are not overhydrated. PMID- 26684443 TI - A Journey in the Development of Gene Therapy for Inherited Disorders of the Bone Marrow. PMID- 26684442 TI - [Influence of polymorphisms of the beta-2 adrenergic receptor on the presence of exercise-induced bronchospasm in adolescents]. AB - OBJECTIVE: To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2) in triggering exercise-induced bronchospasm (EIB) in adolescents. METHODS: The subjects were divided into two groups: present EIB (EIB+) (n=45) and absent EIB (EIB-) (n=115). The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1). The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann-Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. RESULTS: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB- (p<0.05). There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB- groups (p=0.26; p=0.97 and p=0.43, respectively). However, there was a trend towards statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB- group (p=0.08). CONCLUSIONS: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend towards greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents. PMID- 26684444 TI - Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results. AB - Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond. PMID- 26684445 TI - Gene Therapy Briefs. PMID- 26684441 TI - Hepatitis B Virus--Specific and Global T-Cell Dysfunction in Chronic Hepatitis B. AB - BACKGROUND & AIMS: T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). METHODS: We enrolled 200 adults with CHB who participated in the National Institutes of Health-supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. RESULTS: Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3(+)CD127(-) regulatory T cells and CD4(+) T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg)(+) than HBeAg(-) patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg(+) than HBeAg(-) patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. CONCLUSIONS: HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell based immune signatures for clinical phenotypes. These findings suggest additional T-cell-independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation. PMID- 26684446 TI - Preclinical and Preliminary Clinical Evaluation of Genetically Transduced Dermal Tissue Implants for the Sustained Secretion of Erythropoietin and Interferon alpha. AB - Protein drugs are currently delivered by bolus injection and although treatment frequently is successful, these methods also have major drawbacks, which call for the development of alternative technologies allowing prolonged delivery of these drugs. We developed a new ex vivo gene therapy platform called Transduced Autologous Restorative Gene Therapy (TARGT) for sustained long term production and secretion of autologous therapeutic proteins. A biopsy of dermal tissue taken from the patient is transduced ex vivo with a viral vector encoding the required gene under a constitutive promoter. Following measurement of protein secretion ex vivo, the transduced dermal tissue is implanted back into the patient, where it secretes the therapeutic protein into the circulation for several months or longer. A major hurdle to this approach is potential immunogenicity of the transduced tissue following implantation. In this paper we describe the preclinical and early clinical development of this technology, which allowed for overcoming these hurdles. To that end, we have used the helper dependent (HD) adenoviral vector with newly designed expression cassette containing genetic elements to optimize transgene expression. Moreover, we have developed procedures for TARGT tissue implantation, with measures to improve engraftment and reduce inflammation and rejection. Implantation of human TARGT to severe combined immune deficient (SCID) mice indicated long-term production of active proteins in the blood. Preliminary results of a clinical trial from two anemic end-stage renal disease patients, implanted with TARGTs expressing the human erythropoietin (EPO) gene, demonstrated prolonged secretion with physiologic blood level of the hormone and hemoglobin maintenance in the desired range, for a period of at least 5 months without exogenous EPO administration. We believe that the TARGT technology has the potential to become a platform for the sustained delivery of therapeutic proteins in various clinical indications. PMID- 26684448 TI - Corrections to: Hum Gene Ther Clin Dev, 2015 Sep;26(3):165-76. PMID- 26684449 TI - Folding-Generated Molecular Tubes Containing One-Dimensional Water Chains. AB - A series of indolocarbazole-pyridine (IP) oligomers were prepared that fold into helical conformations, and their folding features in solution and in the solid state were revealed. Helical folding of these IP foldamers is induced by dipolar interactions through the ethynyl bond and pi-stacking between two repeating units. Upon helical folding, (1)H NMR signals of aromatic protons were significantly shifted upfield by Deltadelta = 0.5-2.2 ppm. In addition, hypochromic shifts and fluorescence quenching were observed in the absorption and emission spectra. X-ray crystal structures clearly demonstrated that IP foldamers folded to helical structures with cylindrical internal cavities wherein 3 or 5 water molecules were occupied by hydrogen-bonding interactions in a 1-D array, reminiscent of transmembrane water channels, called aquaporins. PMID- 26684447 TI - A GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB. AB - No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease due to defect in alpha-N acetylglucosaminidase (NAGLU). In preparation for a clinical trial, we performed an IND-enabling GLP-toxicology study to assess systemic rAAV9-CMV-hNAGLU gene delivery in WT C57BL/6 mice at 1 * 10(14) vg/kg and 2 * 10(14) vg/kg (n = 30/group, M:F = 1:1), and non-GLP testing in MPS IIIB mice at 2 * 10(14) vg/kg. Importantly, no adverse clinical signs or chronic toxicity were observed through the 6 month study duration. The rAAV9-mediated rNAGLU expression was rapid and persistent in virtually all tested CNS and somatic tissues. However, acute liver toxicity occurred in 33% (5/15) WT males in the 2 * 10(14) vg/kg cohort, which was dose-dependent, sex-associated, and genotype-specific, likely due to hepatic rNAGLU overexpression. Interestingly, a significant dose response was observed only in the brain and spinal cord, whereas in the liver at 24 weeks postinfection (pi), NAGLU activity was reduced to endogenous levels in the high dose cohort but remained at supranormal levels in the low dose group. The possibility of rAAV9 germline transmission appears to be minimal. The vector delivery resulted in transient T-cell responses and characteristic acute antibody responses to both AAV9 and rNAGLU in all rAAV9-treated animals, with no detectable impacts on tissue transgene expression. This study demonstrates a generally safe and effective profile, and may have identified the upper dosing limit of rAAV9-CMV hNAGLU via systemic delivery for the treatment of MPS IIIB. PMID- 26684450 TI - LXRalpha improves myocardial glucose tolerance and reduces cardiac hypertrophy in a mouse model of obesity-induced type 2 diabetes. AB - AIMS/HYPOTHESIS: Diabetic cardiomyopathy is a myocardial disease triggered by impaired insulin signalling, increased fatty acid uptake and diminished glucose utilisation. Liver X receptors (LXRs) are key transcriptional regulators of metabolic homeostasis. However, their effect in the diabetic heart is largely unknown. METHODS: We cloned murine Lxralpha (also known as Nr1h3) behind the alpha-myosin heavy chain (alphaMhc; also known as Myh6) promoter to create transgenic (Lxralpha-Tg) mice and transgene-negative littermates (wild-type [WT]). A mouse model of type 2 diabetes was induced by a high-fat diet (HFD, 60% energy from fat) over 16 weeks and compared with a low-fat diet (10% energy from fat). A mouse model of type 1 diabetes was induced via streptozotocin injection over 12 weeks. RESULTS: HFD manifested comparable increases in body weight, plasma triacylglycerol and insulin resistance per OGTT in Lxralpha-Tg and WT mice. HFD significantly increased left ventricular weight by 21% in WT hearts, but only by 5% in Lxralpha-Tg. To elucidate metabolic effects in the heart, microPET (positron emission tomography) imaging revealed that cardiac glucose uptake was increased by 1.4-fold in WT mice on an HFD, but further augmented by 1.7-fold in Lxralpha-Tg hearts, in part through 5' adenosine monophosphate activated protein kinase (AMPK) phosphorylation and restoration of glucose transporter 4 (GLUT4). By contrast, streptozotocin-induced ablation of insulin signalling diminished cardiac glucose uptake levels and caused cardiac dysfunction, indicating that insulin may be important in LXRalpha-mediated glucose uptake. Chromatin immunoprecipitation assays identified natriuretic peptides, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as potential direct targets of cardiac LXRalpha overexpression. CONCLUSIONS/INTERPRETATION: Cardiac-specific LXRalpha overexpression ameliorates the progression of HFD-induced left ventricular hypertrophy in association with increased glucose reliance and natriuretic peptide signalling during the early phase of diabetic cardiomyopathy. These findings implicate a potential protective role for LXR in targeting metabolic disturbances underlying diabetes. PMID- 26684452 TI - Correction: Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner. PMID- 26684453 TI - Medical Pluralism and Traditional/Complementary and Alternative Medicine Use Among Older People: a Cross-Sectional Study in a Rural Mountainous Village in Japan. AB - Given current concerns about the rapidly aging population in Japan, we investigated medical pluralism and health-seeking behaviors among individuals aged 50 years or older living in a rural mountain village in Japan. In total, 76 participants were interviewed about the methods they used to treat 11 common medical conditions. We found that all the respondents used at least two types of treatment for their medical conditions and nearly 90% used four or five types of treatment. The factors affecting health-seeking behaviors were age, education, car use, and the characteristics of the medical condition. Our results show that the older individuals in this community used both formal and traditional/complementary and alternative medicine (TM/CAM) treatments and did not view issues related to medical care as involving a dualistic choice between formal healthcare services and TM/CAM; however, the relationship between different types of TM/CAM and conventional healthcare varied. PMID- 26684451 TI - Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus. AB - Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2-4% of Western-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short- and long-term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsion-susceptible C57BL/6J mice at post natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm exposed (NT) mice. We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS. We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice. We identify temporal regulation of multiple processes, such as stress-, immune- and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short- and long-term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis. PMID- 26684454 TI - The Wiggle Index: An Open Source Bioassay to Assess Sub-Lethal Insecticide Response in Drosophila melanogaster. AB - Toxicological assays measuring mortality are routinely used to describe insecticide response, but sub-lethal exposures to insecticides can select for resistance and yield additional biological information describing the ways in which an insecticide impacts the insect. Here we present the Wiggle Index (WI), a high-throughput method to quantify insecticide response by measuring the reduction in motility during sub-lethal exposures in larvae of the vinegar fly Drosophila melanogaster. A susceptible wild type strain was exposed to the insecticides chlorantraniliprole, imidacloprid, spinosad, and ivermectin. Each insecticide reduced larval motility, but response times and profiles differed among insecticides. Two sets of target site mutants previously identified in mortality studies on the basis of imidacloprid or spinosad resistance phenotypes were tested. In each case the resistant mutant responded significantly less than the control. The WI was also able to detect a spinosad response in the absence of the primary spinosad target site. This response was not detected in mortality assays suggesting that spinosad, like many other insecticides, may have secondary targets affecting behaviour. The ability of the WI to detect changes in insecticide metabolism was confirmed by overexpressing the imidacloprid metabolizing Cyp6g1 gene in digestive tissues or the central nervous system. The data presented here validate the WI as an inexpensive, generic, sub-lethal assay that can complement information gained from mortality assays, extending our understanding of the genetic basis of insecticide response in D. melanogaster. PMID- 26684457 TI - Parecoxib sodium reduces the need for opioids after tonsillectomy in children: a double-blind placebo-controlled randomized clinical trial. AB - OBJECTIVE: Postoperative pain is a common phenomenon after pediatric tonsillectomy. This prospective randomized double-blind placebo-controlled clinical trial was performed to evaluate the analgesic efficacy of intravenous parecoxib sodium in children undergoing tonsillectomy. METHODS: Sixty children (American Society of Anesthesiologists physical status I-III, aged three to seven years, and scheduled to undergo elective tonsillectomy under general anesthesia) were randomly allocated into one of two groups to receive intravenous parecoxib sodium 1 mg.kg(-1) (Group P, n = 30) or the same volume of saline (Group S, n = 30) just after induction of general anesthesia. Between-group comparisons were made for the number of patients requiring rescue morphine, total number of doses of postoperative rescue morphine, time to first rescue analgesic, postoperative pain and sedation scores, and adverse effects. RESULTS: Rescue morphine was given to more children in Group S (25/30, 83%) than in Group P (17/30, 57%) [relative risk (RR), 1.5; 95% confidence interval (CI), 1.0 to 2.1; P = 0.024]. The mean (SD) time to first rescue analgesic was shorter in Group S than in Group P [132 (54) min vs 193 (78) min, respectively; mean difference, 61; 95% CI, 26.6 to 96.1; P = 0.001]. The median (interquartile range [IQR]) Children's Hospital of Eastern Ontario Pain Scale scores in the postanesthesia care unit were lower in Group P than in Group S (7 [5-8] vs 9 [8-11], respectively; P = 0.001). The incidence of postoperative nausea and vomiting (PONV) was higher in Group S than in Group P [11/30 (37%) vs 4/30 (13%), respectively; RR, 2.8; 95% CI, 1.0 to 7.7; P = 0.037]. CONCLUSIONS: A single intravenous injection of parecoxib sodium 1 mg.kg(-1) after anesthesia induction is an effective method for the control of postoperative pain. It provides a morphine-sparing effect, prolongs the time to first rescue analgesic, and reduces PONV in children undergoing tonsillectomy. PMID- 26684455 TI - Doctor can I buy a new kidney? I've heard it isn't forbidden: what is the role of the nephrologist when dealing with a patient who wants to buy a kidney? AB - Organ trafficking is officially banned in several countries and by the main Nephrology Societies. However, this practice is widespread and is allowed or tolerated in many countries, hence, in the absence of a universal law, the caregiver may be asked for advice, placing him/her in a difficult balance between legal aspects, moral principles and ethical judgments.In spite of the Istanbul declaration, which is a widely shared position statement against organ trafficking, the controversy on mercenary organ donation is still open and some experts argue against taking a negative stance. In the absence of clear evidence showing the clinical disadvantages of mercenary transplantation compared to chronic dialysis, self-determination of the patient (and, with several caveats, of the donor) may conflict with other ethical principles, first of all non maleficence. The present paper was drawn up with the participation of the students, as part of the ethics course at our medical school. It discusses the situation in which the physician acts as a counselor for the patient in the way of a sort of "reverse" informed consent, in which the patient asks advice regarding a complex personal decision, and includes a peculiar application of the four principles (beneficence, non-maleficence, justice and autonomy) to the donor and recipient parties. PMID- 26684458 TI - A novel systematic ABC approach to Diaphragmatic Evaluation (ABCDE). PMID- 26684456 TI - Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein. AB - Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID- 26684459 TI - Interactions between a Candidate Gene for Migration (ADCYAP1), Morphology and Sex Predict Spring Arrival in Blackcap Populations. AB - Avian research has begun to reveal associations between candidate genes and migratory behaviors of captive birds, yet few studies utilize genotypic, morphometric, and phenological data from wild individuals. Previous studies have identified an association between ADCYAP1 polymorphism and autumn migratory behavior (restlessness, or zugunruhe), but little is known about the relationship between ADCYAP1 and spring migratory behavior. The timing of spring migration and arrival to the breeding ground are phenological traits which could be particularly favorable for establishing territories and acquiring mates, thus important to fitness and reproductive success. Here, we investigated how individual genotypic ADCYAP1 variation and phenotypic variation (wing length and shape) of blackcaps (Sylvia atricapilla) affect spring arrival date across nine natural populations in Europe. We hypothesized that longer alleles should be associated with earlier spring arrival dates and expected the effect on arrival date to be stronger for males as they arrive earlier. However, we found that longer wings were associated with earlier spring arrival to the breeding grounds for females, but not for males. Another female-specific effect indicated an interaction between ADCYAP1 allele size and wing pointedness on the response of spring arrival: greater allele size had a positive effect on spring arrival date for females with rounder wings, while a negative effect was apparent for females with more pointed wings. Also, female heterozygotes with pointed wing tips arrived significantly earlier than both homozygotes with pointed wings and heterozygotes with round wings. Stable isotope ratios (delta2H) of a subset of blackcaps captured in Freiburg in 2011 allowed us also to assign individuals to their main overwintering areas in northwest (NW) and southwest (SW) Europe. NW males arrived significantly earlier to the Freiburg breeding site than both SW males and females in 2011. NW females had more pointed wing tips compared to SW females, but no difference in ADCYAP1 allele size was found between the different migration routes. PMID- 26684460 TI - Using Semantic Association to Extend and Infer Literature-Oriented Relativity Between Terms. AB - Relative terms often appear together in the literature. Methods have been presented for weighting relativity of pairwise terms by their co-occurring literature and inferring new relationship. Terms in the literature are also in the directed acyclic graph of ontologies, such as Gene Ontology and Disease Ontology. Therefore, semantic association between terms may help for establishing relativities between terms in literature. However, current methods do not use these associations. In this paper, an adjusted R-scaled score (ARSS) based on information content (ARSSIC) method is introduced to infer new relationship between terms. First, set inclusion relationship between terms of ontology was exploited to extend relationships between these terms and literature. Next, the ARSS method was presented to measure relativity between terms across ontologies according to these extensional relationships. Then, the ARSSIC method using ratios of information shared of term's ancestors was designed to infer new relationship between terms across ontologies. The result of the experiment shows that ARSS identified more pairs of statistically significant terms based on corresponding gene sets than other methods. And the high average area under the receiver operating characteristic curve (0.9293) shows that ARSSIC achieved a high true positive rate and a low false positive rate. Data is available at http://mlg.hit.edu.cn/ARSSIC/. PMID- 26684461 TI - On Efficient Feature Ranking Methods for High-Throughput Data Analysis. AB - Efficient mining of high-throughput data has become one of the popular themes in the big data era. Existing biology-related feature ranking methods mainly focus on statistical and annotation information. In this study, two efficient feature ranking methods are presented. Multi-target regression and graph embedding are incorporated in an optimization framework, and feature ranking is achieved by introducing structured sparsity norm. Unlike existing methods, the presented methods have two advantages: (1) the feature subset simultaneously account for global margin information as well as locality manifold information. Consequently, both global and locality information are considered. (2) Features are selected by batch rather than individually in the algorithm framework. Thus, the interactions between features are considered and the optimal feature subset can be guaranteed. In addition, this study presents a theoretical justification. Empirical experiments demonstrate the effectiveness and efficiency of the two algorithms in comparison with some state-of-the-art feature ranking methods through a set of real-world gene expression data sets. PMID- 26684462 TI - Predicting Protein-Protein Interaction Sites with a Novel Membership Based Fuzzy SVM Classifier. AB - Predicting residues that participate in protein-protein interactions (PPI) helps to identify, which amino acids are located at the interface. In this paper, we show that the performance of the classical support vector machine (SVM) algorithm can further be improved with the use of a custom-designed fuzzy membership function, for the partner-specific PPI interface prediction problem. We evaluated the performances of both classical SVM and fuzzy SVM (F-SVM) on the PPI databases of three different model proteomes of Homo sapiens, Escherichia coli and Saccharomyces Cerevisiae and calculated the statistical significance of the developed F-SVM over classical SVM algorithm. We also compared our performance with the available state-of-the-art fuzzy methods in this domain and observed significant performance improvements. To predict interaction sites in protein complexes, local composition of amino acids together with their physico-chemical characteristics are used, where the F-SVM based prediction method exploits the membership function for each pair of sequence fragments. The average F-SVM performance (area under ROC curve) on the test samples in 10-fold cross validation experiment are measured as 77.07, 78.39, and 74.91 percent for the aforementioned organisms respectively. Performances on independent test sets are obtained as 72.09, 73.24 and 82.74 percent respectively. The software is available for free download from http://code.google.com/p/cmater-bioinfo. PMID- 26684463 TI - Growth Signatures of Rosette Plants from Time-Lapse Video. AB - Plant growth is a dynamic process, and the precise course of events during early plant development is of major interest for plant research. In this work, we investigate the growth of rosette plants by processing time-lapse videos of growing plants, where we use Nicotiana tabacum (tobacco) as a model plant. In each frame of the video sequences, potential leaves are detected using a leaf shape model. These detections are prone to errors due to the complex shape of plants and their changing appearance in the image, depending on leaf movement, leaf growth, and illumination conditions. To cope with this problem, we employ a novel graph-based tracking algorithm which can bridge gaps in the sequence by linking leaf detections across a range of neighboring frames. We use the overlap of fitted leaf models as a pairwise similarity measure, and forbid graph edges that would link leaf detections within a single frame. We tested the method on a set of tobacco-plant growth sequences, and could track the first leaves of the plant, including partially or temporarily occluded ones, along complete sequences, demonstrating the applicability of the method to automatic plant growth analysis. All seedlings displayed approximately the same growth behavior, and a characteristic growth signature was found. PMID- 26684464 TI - Zoophagic behaviour of anopheline mosquitoes in southwest Ethiopia: opportunity for malaria vector control. AB - BACKGROUND: Increased understanding of the feeding behaviours of malaria vectors is important to determine the frequency of human-vector contact and to implement effective vector control interventions. Here we assess the relative feeding preferences of Anopheles mosquitoes in relation to cattle and human host abundance in southwest Ethiopia. METHODS: We collected female Anopheles mosquitoes bi-weekly using Centers for Disease Control and prevention (CDC) light traps, pyrethrum spray catches (PSCs) and by aspirating from artificial pit shelters, and determined mosquito blood meal origins using a direct enzyme-linked immunosorbent assay (ELISA). RESULTS: Both Anopheles arabiensis Patton and An. marshalli (Theobald) showed preference of bovine blood meal over humans regardless of higher human population sizes. The relative feeding preference of An. arabiensis on bovine blood meal was 4.7 times higher than that of human blood. Anopheles marshalli was 6 times more likely to feed on bovine blood meal than humans. The HBI of An. arabiensis and An. marshalli significantly varied between the collection methods, whereas the bovine feeding patterns was not substantially influenced by collection methods. Even though the highest HBI of An. arabiensis and An. marshalli was from indoor CDC traps collections, a substantial number of An. arabiensis (65%) and An. marshalli (63%) had contact with cattle. Anopheles arabiensis (44%) and An. marshalli (41%) had clearly taken bovine blood meals outdoors, but they rested indoors. CONCLUSION: Anopheles mosquitoes are zoophagic and mainly feed on bovine blood meals than humans. Hence, it is important to consider treatment of cattle with appropriate insecticide to control the zoophagic malaria vectors in southwest Ethiopia. Systemic insecticides like ivermectin and its member eprinomectin could be investigated to control the pyrethroid insecticides resistant vectors. PMID- 26684465 TI - Seed Dormancy in Arabidopsis Requires Self-Binding Ability of DOG1 Protein and the Presence of Multiple Isoforms Generated by Alternative Splicing. AB - The Arabidopsis protein DELAY OF GERMINATION 1 (DOG1) is a key regulator of seed dormancy, which is a life history trait that determines the timing of seedling emergence. The amount of DOG1 protein in freshly harvested seeds determines their dormancy level. DOG1 has been identified as a major dormancy QTL and variation in DOG1 transcript levels between accessions contributes to natural variation for seed dormancy. The DOG1 gene is alternatively spliced. Alternative splicing increases the transcriptome and proteome diversity in higher eukaryotes by producing transcripts that encode for proteins with altered or lost function. It can also generate tissue specific transcripts or affect mRNA stability. Here we suggest a different role for alternative splicing of the DOG1 gene. DOG1 produces five transcript variants encoding three protein isoforms. Transgenic dog1 mutant seeds expressing single DOG1 transcript variants from the endogenous DOG1 promoter did not complement because they were non-dormant and lacked DOG1 protein. However, transgenic plants overexpressing single DOG1 variants from the 35S promoter could accumulate protein and showed complementation. Simultaneous expression of two or more DOG1 transcript variants from the endogenous DOG1 promoter also led to increased dormancy levels and accumulation of DOG1 protein. This suggests that single isoforms are functional, but require the presence of additional isoforms to prevent protein degradation. Subsequently, we found that the DOG1 protein can bind to itself and that this binding is required for DOG1 function but not for protein accumulation. Natural variation for DOG1 binding efficiency was observed among Arabidopsis accessions and contributes to variation in seed dormancy. PMID- 26684466 TI - Zika virus: a previously slow pandemic spreads rapidly through the Americas. AB - Zika virus (family Flaviviridae) is an emerging arbovirus. Spread by Aedes mosquitoes, it was first discovered in Uganda in 1947, and later in humans elsewhere in sub-Saharan Africa, arriving in south-east Asia at latest by the mid twentieth century. In the twenty-first century, it spread across the Pacific islands reaching South America around 2014. Since then it has spread rapidly northwards reaching Mexico in November 2015. Its clinical profile is that of a dengue-like febrile illness, but associations with Guillain-Barre syndrome and microcephaly have appeared recently. The final geographical range and ultimate clinical impact of Zika virus are still a matter for speculation. PMID- 26684467 TI - Environment and Brain Development: Challenges in the Global Context. PMID- 26684469 TI - A cohort study comparing the serum levels of pro- or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects. AB - PURPOSE: The factors influencing the presence or absence of pain in sciatica secondary to disc herniation remain incompletely understood. We hypothesized that the imbalance in inflammatory cytokines is implicated in the generation of pain. In our study, serum levels of pro-inflammatory and anti-inflammatory cytokines were investigated among patients with severe sciatica; the serum levels were compared with those of patients with mild sciatica and healthy subjects. METHODS: In this prospective study, blood protein levels of the pro-inflammatory cytokines, namely, interleukin-6 (IL-6), interleukin-8 (IL-8),and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokines, namely, interleukin-4 (IL-4) and interleukin-10 (IL-10), of 58 patients with severe sciatica, 50 patients with mild sciatica, and 30 healthy control subjects were analyzed through ELISA. Physical and mental health symptoms were determined using the Oswestry Disability Index (ODI) and short form-36 (SF-36) questionnaire. Spearman rank correlation coefficient was also determined to calculate the correlation between the scores obtained from the questionnaires and the serum levels of cytokines. RESULTS: IL-6 protein was detected in the three groups and median levels were about 1.5 times higher in patients with severe sciatica than the mild sciatica group (p = 0.02) and the controls (p = 0.03). Median levels of IL-8 in sciatica patients were higher than those of the healthy controls (p = 0.001 for severe sciatica, p = 0.02 for mild sciatica). The TNF-alpha protein values were approximately twofold higher in the severe sciatica group than in the mild sciatica group (p < 0.01) and in the healthy control group (p < 0.01). Median levels of IL-4 were about 2.5-fold higher in mild sciatica (p < 0.01) and about twofold higher in patients with severe sciatica (p = 0.012) when compared with controls. Median protein levels of IL-10 showed a trend to be higher in patients with mild sciatica compared with severe sciatica (p < 0.01) and with healthy controls (p < 0.01). ODI was significantly correlated with IL-6 (r = 0.394, p = 0.013), TNF-alpha (r = 0.629, p < 0.001), and IL-10 (r = -0.415, p = 0.009). ODI was not significantly correlated with IL-4 (r = -0.174, p = 0.29) and IL-8 (r = -0.133, p = 0.418). CONCLUSIONS: These findings support our hypothesis that sciatica pain is accompanied by the imbalance in inflammatory cytokines. PMID- 26684468 TI - In vitro investigation of a new dynamic cervical implant: comparison to spinal fusion and total disc replacement. AB - PURPOSE AND METHODS: For the treatment of degenerative disc diseases of the cervical spine, anterior cervical discectomy and fusion (ACDF) still represents the standard procedure. However, long term clinical studies have shown a higher incidence of pathologies in the adjacent segments. As an alternative to spinal fusion, cervical total disc replacement (cTDR) or dynamically implants were increasingly used. This in vitro study analyzed the kinematics and intradiscal pressures in seven multi-segmental human cervical spine using hybrid multidirectional test method. The aim of our study was to compare the intact condition with a single-level dynamic stabilization with DCI((r)), with cTDR (activC((r))) and with simulated ACDF (CeSPACE((r)) cage and CASPAR plate). RESULTS: No significant changes in the kinematics and pressures were observed in all segments after arthroplasty. The DCI((r)) significantly decreased the motion of the treated segment in flexion/extension and lateral bending with some remaining residual mobility. Thereby the motion of the upper segment was increased significantly in flexion/extension. No significant changes of the intradiscal pressures were observed. With simulated fusion the motion of the indexed level was significantly decreased in flexion/extension and axial rotation with the greatest changes in the adjacent levels and the highest pressures. CONCLUSION: Based on our biomechanical study the DCI((r)) can pose an alternative to fusion, which has a lesser effect on adjacent levels. This might reduce the risk of long-term degeneration in those levels. In particular, the facet joint arthritis and kyphotic deformity, as a contraindication to the arthroplasty, could be a clinical application of the dynamic implant. PMID- 26684470 TI - Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. AB - BACKGROUND: Predicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used. RESULTS: Basal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7%, 30.6%, 18.2%, and 10.3% of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2 positive disease, and in TNBC. The pCR rate of Basal-like disease was >35% across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5% (92.8-100.0%) was observed in these neoadjuvant treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4% of Luminal A tumors with clinically node-negative disease). CONCLUSIONS: Intrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any). PMID- 26684472 TI - Processes of change in Acceptance and Commitment Therapy and Applied Relaxation for long-standing pain. AB - BACKGROUND: The utility of cognitive behavioural (CB) interventions for chronic pain has been supported in numerous studies. This includes Acceptance and Commitment Therapy (ACT), which has gained increased empirical support. Previous research suggests that improvements in pain catastrophizing and psychological inflexibility are related to improvements in treatment outcome in this type of treatment. Although a few studies have evaluated processes of change in CB interventions, there is a particular need for mediation analyses that use multiple assessments to model change in mediators and outcome over time, and that incorporate the specified timeline between mediator and outcome in the data analytic model. METHODS: This study used session-to-session assessments to evaluate if psychological inflexibility, catastrophizing, and pain intensity mediated the effects of treatment on pain interference. Analyses were based on data from a previously conducted randomized controlled trial (n = 60) evaluating the efficacy of ACT and Applied Relaxation (AR). A moderated mediation model based on linear mixed models was used to analyse the data. RESULTS: Neither catastrophizing nor pain intensity mediated changes in pain interference for any of the treatments. In contrast, psychological inflexibility mediated effects on outcome in ACT but not in AR. CONCLUSIONS: Results add to previous findings illustrating the role of psychological inflexibility as a mediator in ACT. PMID- 26684473 TI - Experimental Designs and the 'Emotion Stimulus Critique': Hidden Problems and Potential Solutions in the Study of Emotion. AB - Emotional experience is increasingly being measured using experimental tasks, but the stimuli used are often only proxies for the emotion being studied. Stimuli are intended to evoke a distinct emotional experience, but certain designs fail to adequately control for the actual experience in question. In this methodological paper, we review designs used in clinical psychology aimed at measuring emotion and develop the argument of the 'emotion stimulus critique'. Designs of neuroimaging studies on emotion in this context are given preference. We argue that studies often concentrate on standardization of the stimulus material (i.e. words, images, and movies) for eliciting an emotional experience, whereas standardization of the actual participant's experience is seldom performed. Our proposal discusses the use of standardized stimuli in experimental designs and contrasts this with the necessity of controlling for a participant's unique emotional response. We highlight the importance of each participant's 'inner metric', i.e. the individual's experiential anchor, which needs to be taken into account when examining the emotional correlates of psychiatric disorders or psychotherapeutic change. Implications of the emotion stimulus critique for research are discussed within the context of psychology, particularly clinical psychology and psychotherapy. PMID- 26684475 TI - Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism. AB - BACKGROUND AND OBJECTIVE: Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD). METHODS: In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD. Random spot urine screening for creatine metabolites (creatine, guanidinoacetate, creatinine, and arginine) with liquid chromatography-tandem mass spectrometry and second-tier testing with high-performance liquid chromatography methodology was followed by recall testing in 24-hour urines and confirmatory testing by Sanger-based DNA sequencing of GAMT, GATM, and SLC6A8 genes. Additional diagnostic tests included plasma creatine metabolites and in vivo brain proton magnetic resonance spectroscopy. The creatine metabolites in spot urine in the autism group were compared with 128 healthy controls controlled for age. RESULTS: In 443 subjects with ASD investigated for CDS, we had 0 events (event: 0, 95% confidence interval 0-0.0068), therefore with 95% confidence the prevalence of CDS is <7 in 1000 children with ASD. The autism and control groups did not vary in terms of creatine metabolites (P > .0125) in urine. CONCLUSION: Our study revealed a very low prevalence of CDS in children with nonsyndromic ASD and no obvious association between creatine metabolites and autism. Unlike our study population, we expect more frequent CDS among children with severe developmental delay, speech impairment, seizures, and movement disorders in addition to impairments in social communication, restricted interests, and repetitive behaviors. PMID- 26684471 TI - Approaches to improving the contribution of the nursing and midwifery workforce to increasing universal access to primary health care for vulnerable populations: a systematic review. AB - BACKGROUND: Despite considerable evidence showing the importance of the nursing and midwifery workforce, there are no systematic reviews outlining how these cadres are best supported to provide universal access and reduce health care disparities at the primary health care (PHC) level. This review aims to identify nursing and midwifery policy, staffing, education and training interventions, collaborative efforts and strategies that have improved the quantity, quality and relevance of the nursing and midwifery workforce leading to health improvements for vulnerable populations. METHODS: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to analyse the interventions and findings of included studies using a conceptual framework. RESULTS: Thirty-six papers were included in the review, the majority (25) from high-income countries and nursing settings (32). Eleven papers defined leadership and governance approaches that had impacted upon the health outcomes of disadvantaged groups including policies at the national and state level that had led to an increased supply and coverage of nursing and midwifery staff and scope of practice. Twenty-seven papers outlined human resource management strategies to support the expansion of nurse's and midwives' roles that often involved task shifting and task sharing. These included approaches to managing staffing supply, distribution and skills mix; workloads; supervision; performance management; and remuneration, financial incentives and staffing costs. Education and training activities were described in 14 papers to assist nurses and midwives to perform new or expanded roles and prepare nurses for inclusive practice. This review identified collaboration between nurses and midwives and other health providers and organizations, across sectors, and with communities and individuals that resulted in improved health care and outcomes. CONCLUSIONS: The findings of this review confirm the importance of a conceptual framework for understanding and planning leadership and governance approaches, management strategies and collaboration and education and training efforts to scale up and support nurses and midwives in existing or expanded roles to improve access to PHC for vulnerable populations. PMID- 26684476 TI - Sign Language and Spoken Language for Children With Hearing Loss: A Systematic Review. AB - CONTEXT: Permanent hearing loss affects 1 to 3 per 1000 children and interferes with typical communication development. Early detection through newborn hearing screening and hearing technology provide most children with the option of spoken language acquisition. However, no consensus exists on optimal interventions for spoken language development. OBJECTIVE: To conduct a systematic review of the effectiveness of early sign and oral language intervention compared with oral language intervention only for children with permanent hearing loss. DATA SOURCES: An a priori protocol was developed. Electronic databases (eg, Medline, Embase, CINAHL) from 1995 to June 2013 and gray literature sources were searched. Studies in English and French were included. STUDY SELECTION: Two reviewers screened potentially relevant articles. DATA EXTRACTION: Outcomes of interest were measures of auditory, vocabulary, language, and speech production skills. All data collection and risk of bias assessments were completed and then verified by a second person. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to judge the strength of evidence. RESULTS: Eleven cohort studies met inclusion criteria, of which 8 included only children with severe to profound hearing loss with cochlear implants. Language development was the most frequently reported outcome. Other reported outcomes included speech and speech perception. LIMITATIONS: Several measures and metrics were reported across studies, and descriptions of interventions were sometimes unclear. CONCLUSIONS: Very limited, and hence insufficient, high-quality evidence exists to determine whether sign language in combination with oral language is more effective than oral language therapy alone. More research is needed to supplement the evidence base. PMID- 26684477 TI - Science, Not Philosophy, Will Help Deaf and Hard-of-Hearing Children Reach Their Potential. PMID- 26684478 TI - School-Based Mindfulness Instruction: An RCT. AB - BACKGROUND AND OBJECTIVE: Many urban youth experience significant and unremitting negative stressors, including those associated with community violence, multigenerational poverty, failing educational systems, substance use, limited avenues for success, health risks, and trauma. Mindfulness instruction improves psychological functioning in a variety of adult populations; research on mindfulness for youth is promising, but has been conducted in limited populations. Informed by implementation science, we evaluated an adapted mindfulness-based stress reduction (MBSR) program to ameliorate the negative effects of stress and trauma among low-income, minority, middle school public school students. METHODS: Participants were students at two Baltimore City Public Schools who were randomly assigned by grade to receive adapted MBSR or health education (Healthy Topics [HT]) programs. Self-report survey data were collected at baseline and postprogram. Deidentified data were analyzed in the aggregate, comparing MBSR and HT classes, by using regression modeling. RESULTS: Three hundred fifth- to eighth-grade students (mean 12.0 years) were in MBSR and HT classes and provided survey data. Participants were 50.7% female, 99.7% African American, and 99% eligible for free lunch. The groups were comparable at baseline. Postprogram, MBSR students had significantly lower levels of somatization, depression, negative affect, negative coping, rumination, self hostility, and posttraumatic symptom severity (all Ps < .05) than HT. CONCLUSIONS: These findings support the hypothesis that mindfulness instruction improves psychological functioning and may ameliorate the negative effects of stress and reduce trauma-associated symptoms among vulnerable urban middle school students. Additional research is needed to explore psychological, social, and behavioral outcomes, and mechanisms of mindfulness instruction. PMID- 26684479 TI - A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient. AB - Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) enzyme deficiency, which leads to the accumulation of toxic metabolites that impair lymphocyte development and function. With the development of polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) enzyme replacement therapy, many ADA-deficient children with SCID who could not receive a hematopoietic stem cell transplantation or gene therapy survived and had longer and healthier lives. We report a 24-year course of treatment in a patient who was diagnosed with ADA deficiency at 4 months of age. The patient was treated with PEG-ADA, which was the only therapy available for him. The patient's plasma ADA level was regularly monitored and the PEG-ADA dose adjusted accordingly. This treatment has resulted in near-normalization of lymphocyte counts, and his clinical course has been associated with only minor to moderate infections. Thus far, he has had no manifestations of autoimmune or lymphoproliferative disorders. This patient is among the longest to be maintained on PEG-ADA enzyme replacement therapy. PMID- 26684480 TI - Whether screening for ovarian cancer saves lives is still unclear despite large trial. PMID- 26684481 TI - Gene Therapy for Rare Central Nervous System Diseases Comes to Age. AB - Gene therapy for rare inherited neurologic diseases has entered the clinics. One strategy relies upon the replacement of brain microglia using hematopoietic stem cell gene therapy with lentiviral vectors. Therapeutic success using this approach has been obtained in X-linked adrenoleukodystrophy and metachromatic leukodystrophy. The other strategy relies upon the intracerebral administration of adeno-associated virus vectors encoding lysosomal enzymes. Therapeutic trials are ongoing in Batten's disease, metachromatic leukodystrophy, and Sanfilippo type A and B diseases. PMID- 26684482 TI - Evaluation of Natural and Synthetic 1,4-naphthoquinones as Inhibitors of Monoamine Oxidase. AB - Previous reports have documented that 1,4-naphthoquinones act as inhibitors of the monoamine oxidase (MAO) enzymes. In particular, fractionation of the extracts of cured tobacco leafs has led to the characterization of 2,3,6-trimethyl-1,4 naphthoquinone, a non-selective MAO inhibitor. To derive structure-activity relationships for MAO inhibition by the 1,4-naphthoquinone class of compounds, this study investigates the human MAO inhibitory activities of fourteen structurally diverse 1,4-naphthoquinones of natural and synthetic origin. Of these, 5,8-dihydroxy-1,4-naphthoquinone was found to be the most potent inhibitor with an IC50 value of 0.860 MUm for the inhibition of MAO-B. A related compound, shikonin, inhibits both the MAO-A and MAO-B isoforms with IC50 values of 1.50 and 1.01 MUm, respectively. It is further shown that MAO-A and MAO-B inhibition by these compounds is reversible by dialysis. In this respect, kinetic analysis suggests that the modes of MAO inhibition are competitive. This study contributes to the discovery of novel MAO inhibitors, which may be useful in the treatment for disorders such as Parkinson's disease, depressive illness, congestive heart failure and cancer. PMID- 26684485 TI - Upper gastrointestinal endoscopy in ferret and the histological assessment of the endoscopic biopsies. PMID- 26684484 TI - Tissues from equine cadaver ligaments up to 72 hours of post-mortem: a promising reservoir of stem cells. AB - BACKGROUND: Mesenchymal stem cells (MSCs) harvested from cadaveric tissues represent a promising approach for regenerative medicine. To date, no study has investigated whether viable MSCs could survive in cadaveric tissues from tendon or ligament up to 72 hours of post-mortem. The purpose of the present work was to find out if viable MSCs could survive in cadaveric tissues from adult equine ligaments up to 72 hours of post-mortem, and to assess their ability (i) to remain in an undifferentiated state and (ii) to divide and proliferate in the absence of any specific stimulus. METHODS: MSCs were isolated from equine cadaver (EC) suspensory ligaments within 48-72 hours of post-mortem. They were evaluated for viability, proliferation, capacity for tri-lineage differentiation, expression of cell surface markers (CD90, CD105, CD73, CD45), pluripotent transcription factor (OCT-4), stage-specific embryonic antigen-1 (SSEA-1), neuron specific class III beta-tubulin (TUJ-1), and glial fibrillary acidic protein (GFAP). As well, they were characterized by transmission electron microscope (TEM). RESULTS: EC-MSCs were successfully isolated and maintained for 20 passages with high cell viability and proliferation. Phase contrast microscopy revealed that cells with fibroblast-like appearance were predominant in the culture. Differentiation assays proved that EC-MSCs are able to differentiate towards mesodermal lineages (osteogenic, adipogenic, chondrogenic). Flow cytometry analysis demonstrated that EC-MSCs expressed CD90, CD105, and CD73, while being negative for the leukocyte common antigen CD45. Immunofluorescence analysis showed a high percentage of positive cells for OCT-4 and SSEA-1. Surprisingly, in absence of any stimuli, some adherent cells closely resembling neuronal and glial morphology were also observed. Interestingly, our results revealed that approximately 15 % of the cell populations were TUJ-1 positive, whereas GFAP expression was detected in only a few cells. Furthermore, TEM analysis confirmed the stemness of EC-MSCs and identified some cells with a typical neuronal morphology. CONCLUSIONS: Our findings raise the prospect that the tissues harvested from equine ligaments up to 72 hours of post-mortem represent an available reservoir of specific stem cells. EC-MSCs could be a promising alternative source for tissue engineering and stem cell therapy in equine medicine. PMID- 26684483 TI - Light-Activated Reversible Imine Isomerization: Towards a Photochromic Protein Switch. AB - Mutants of cellular retinoic acid-binding protein II (CRABPII), engineered to bind all-trans-retinal as an iminium species, demonstrate photochromism upon irradiation with light at different wavelengths. UV light irradiation populates the cis-imine geometry, which has a high pKa , leading to protonation of the imine and subsequent "turn-on" of color. Yellow light irradiation yields the trans-imine isomer, which has a depressed pKa , leading to loss of color because the imine is not protonated. The protein-bound retinylidene chromophore undergoes photoinduced reversible interconversion between the colored and uncolored species, with excellent fatigue resistance. PMID- 26684486 TI - Revisiting tuberculosis risk in Peace Corps Volunteers, 2006-13. AB - BACKGROUND: Risk of tuberculosis (TB) is generally considered to be low for long term travellers, though risk varies with travel destination, duration and purpose. Peace Corps Volunteers (PCVs) serve for 27 months as community-level development workers in various countries around the world and may be exposed to TB in the course of their service. This study examines recent trends in TB in PCVs and compares rates with a previous analysis published by Jung and Banks. METHODS: Tuberculosis case data submitted to the Peace Corps' Epidemiologic Surveillance System by Peace Corps Medical Officers and gathered from Federal Employees Compensation Act claims for latent TB infection (LTBI) and active TB between 2006 and 2013 were aggregated and analysed for trends and significance. RESULTS: Overall, there were 689 cases of LTBI and 13 cases of active TB, for a rate of 0.95 cases of LTBI [95% confidence interval (CI) 0.88-1.02] and 0.02 cases of active TB (95% CI 0.01-0.03) per 1000 Volunteer-months. Both are significantly lower than rates presented in the initial study (P < 0.001). Per country incidence rates for LTBI ranged from 0.00 to 4.52 cases per 1000 Volunteer-months. Per-country active TB rates ranged from 0.00 to 0.78 cases per 1000 Volunteer-months. Among the 13 cases of active TB, there was one successfully treated case of extensively drug-resistant TB. CONCLUSIONS: Overall rates of both active and latent TB in PCVs were significantly lower compared with the previous study period. PCVs continue to have statistically significantly higher rates of active TB compared with the general US population but lower rates compared with other long-term travellers. PMID- 26684488 TI - Are you practicing dogma? PMID- 26684489 TI - Clinical issues in occlusion - Part II. AB - Occlusal diagnosis plays an important role in the planning and subsequent delivery of predictable functional and aesthetic restorations and prostheses. Once an occlusal problem is identified there are a number of techniques and materials that can be utilised to record occlusal relationships, subsequently analyse them and incorporate information obtained into the delivery of tooth restoration or replacement. This paper discusses the clinical and technical aspects of occlusal examination and analysis outlining contemporary and traditional techniques in their utilisation. Aspects of occlusal examination will be revisited; the identification and recording of centric occlusion as well as subsequent articulation will be discussed. The requirement for occlusal splint provision will also be discussed and illustrated. PMID- 26684487 TI - Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine. AB - Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. PMID- 26684490 TI - Dry mouth - An overview. AB - This paper presents an overview of dry mouth, an important condition in the older population. Dry mouth will first be defined, followed by consideration of its occurrence. There will then be an overview of the leading causes of dry mouth. Next, the impact of dry mouth will be discussed in order to explain why it is a significant condition. Lastly, there will be a brief description of the diagnosis and management of dry mouth. PMID- 26684491 TI - MicroRNAs as biomarkers for dental diseases. AB - MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators of diverse biological processes by mediating translational repression or mRNA degradation of target genes. Recent studies discovered miRNAs in saliva, and these miRNAs are promising candidates for use as biomarkers of dental diseases. In this review, the results of miRNA studies in the dental field are presented, and a brief overview of the current progress, limitations, and perspectives regarding miRNA biomarkers for dental diseases is given. PMID- 26684492 TI - Utilization of extracted teeth as provisional restorations following immediate implant placement - A case report. AB - This case report utilized a patient's natural teeth as provisional restorations supported by immediately placed implants to provide a seamless transition from hopeless teeth to implant supported restorations. PMID- 26684493 TI - Comparison of incidence of dentinal defects after root canal preparation with continuous rotation and reciprocating instrumentation. AB - Biomechanical preparation is one of the most important steps in endodontic therapy. Rotary instrumentation has facilitated this step. Nowadays the market is flooded with different types of rotary instruments. The present study compared the root dentinal crack formation with continuous rotating versus reciprocating root canal preparation methods. One hundred and fifty freshly extracted teeth were used for the study. They were divided into 5 groups with 30 teeth in each group. Thirty teeth were kept under control group A and no root canal preparation was done for this group. Another 30 teeth were prepared with hand files which were kept under control group B. In the experimental groups (sample size, n=30 each) root canals were prepared with ProTaper, K3XF rotary system and WaveOne. Sectioning of these teeth was done at 3, 6 and 9mm from the apex and were evaluated for the presence of any defects. Root dentinal cracks were produced with each type of rotary instruments. Statistical analysis showed no significant difference in root dentinal crack formation between control groups and WaveOne system. There was statistically significant difference in root dentinal crack formation when the canals were prepared with ProTaper and K3XF rotary system. So it was concluded, that continuous rotating instruments could produce dentinal crack formation. Root canal instruments with reciprocating movement appear to be a better option than continuous rotation movement. PMID- 26684494 TI - Necrotizing periodontitis in a heavy smoker and tobacco chewer - A case report. AB - Necrotizing periodontitis is a distinct and specific disease characterized by rapidly progressing ulceration of the interdental gingiva and then spreading along the gingival margins and leading to acute destruction of periodontal tissues. Necrotizing ulcerative gingival lesions are common in developing countries because of poor nutritional status, poor oral hygiene and debilitating conditions. In the developed world it is mostly seen in patients with the HIV infections and other immune system dysfunctions. The exact etiology of the necrotizing lesions is still unknown; however a fuso-spirochaetal infection along with weakened host immune system seems to play a major role in the pathogenesis of these diseases. Presented is the case of acute necrotizing periodontitis in a 21 year old male patient with no systemic disease but a history of tobacco use (chewing and smoking) since 7 years. The patient was managed by conservative treatment followed by surgery for the correction of gingival defects. PMID- 26684495 TI - Application of platelet rich fibrin for management of an electrosurge induced osteonecrosis involving maxillary alveolus. AB - BACKGROUND: Application of principles of electrocautery for hemostasis dates back to prehistoric times. Its modern implementation in various fields of general and head and neck surgeries have been well documented. However its usage in minor oral surgical procedures has gained popularity only recently. Complications associated with electro-surgery in the dental field are relatively rare and there is insufficient literature on its management. CASE REPORT: We present a case report on management of an electrosurgery induced osteonecrosis involving maxillary alveolus of left premolars. DISCUSSION: Inadvertent contact of the electrosurgery tip on bone can result in necrosis making it necessary to remove the sequestrum and graft the defect. Platelet rich fibrin in combination with bone grafts have been well documented to provide successful periodontal regeneration. CLINICAL IMPLICATIONS: Our aim of presenting this report is to create awareness among the health care providers regarding electrosurgical injuries. To our knowledge, this is the first time platelet rich fibrin has been used in the management of intraoral electrosurgical injury. Combining bone grafts with platelet rich fibrin is a good alternative as it can be done with relative ease and predictable outcome. PMID- 26684496 TI - Rapid fabrication of a digital prosthesis. AB - Finger prosthesis often needs refabrication due to its discoloration following use. This article presents a novel, economical, and cost-effective technique to duplicate the patient's existing prosthesis to obtain a new wax replica, which is then clinically tried and processed to obtain new silicone finger prosthesis. This technique requires comparatively less clinical and laboratory steps as to fabricate an entirely new prosthesis. The newly fabricated silicone finger prosthesis has the fit and marginal adaptation of the patient's existing prosthesis but the esthetics is improved. PMID- 26684497 TI - Parental resolution and the adolescent's health and adjustment: The case of adolescents with type 1 diabetes. AB - This study examines the association between parents' resolution of their adolescent child's diagnosis of type 1 diabetes and the health and mental adjustment of the adolescents themselves. Parents of 75 adolescents with type 1 diabetes were interviewed using the Reaction to Diagnosis Interview. Parents and adolescents completed questionnaires regarding the child's physical health, self management of the disease, and behavioral and emotional problems. Physicians reported adolescents' HbA1c levels. Results showed that adolescents whose fathers were resolved with the diagnosis exhibited better diabetes self-management and adolescents whose mothers were resolved with the diagnosis exhibited fewer internalizing and externalizing problems. The findings highlight the different role of mothers and fathers in the treatment of adolescents with diabetes and provide a basis for clinical intervention that focuses not only on adolescent health, but also on parental state of mind regarding the resolution with the disease. PMID- 26684498 TI - Contribution of Major Metabolites toward Complex Drug-Drug Interactions of Deleobuvir: In Vitro Predictions and In Vivo Outcomes. AB - The drug-drug interaction (DDI) potential of deleobuvir, an hepatitis C virus (HCV) polymerase inhibitor, and its two major metabolites, CD 6168 (formed via reduction by gut bacteria) and deleobuvir-acyl glucuronide (AG), was assessed in vitro. Area-under-the-curve (AUC) ratios (AUCi/AUC) were predicted using a static model and compared with actual AUC ratios for probe substrates in a P450 cocktail of caffeine (CYP1A2), tolbutamide (CYP2C9), and midazolam (CYP3A4), administered before and after 8 days of deleobuvir administration to HCV-infected patients. In vitro studies assessed inhibition, inactivation and induction of P450s. Induction was assessed in a short-incubation (10 hours) hepatocyte assay, validated using positive controls, to circumvent cytotoxicity seen with deleobuvir and its metabolites. Overall, P450 isoforms were differentially affected by deleobuvir and its two metabolites. Of note was more potent CYP2C8 inactivation by deleobuvir-AG than deleobuvir and P450 induction by CD 6168 but not by deleobuvir. The predicted net AUC ratios for probe substrates were 2.92 (CYP1A2), 0.45 (CYP2C9), and 0.97 (CYP3A4) compared with clinically observed ratios of 1.64 (CYP1A2), 0.86 (CYP2C9), and 1.23 (CYP3A4). Predictions of DDI using deleobuvir alone would have significantly over-predicted the DDI potential for CYP3A4 inhibition (AUC ratio of 6.15). Including metabolite data brought the predicted net effect close to the observed DDI. However, the static model over-predicted the induction of CYP2C9 and inhibition/inactivation of CYP1A2. This multiple perpetrator DDI scenario highlights the application of the static model for predicting complex DDI for CYP3A4 and exemplifies the importance of including key metabolites in an overall DDI assessment. PMID- 26684499 TI - Effects of Phenobarbital on Expression of UDP-Glucuronosyltransferase 1a6 and 1a7 in Rat Brain. AB - UDP-glucuronosyltransferase (UGT), a phase II drug-metabolizing enzyme, is expressed in the brain and can catalyze glucuronidation of endogenous and exogenous substrates in the brain. Thus, changes in UGT1A expression could affect homeostasis and drug efficacy. Phenobarbital (PB), a typical inducer of drug metabolizing enzymes, has been reported to induce oxidative stress and epigenetic changes, which could alter UGT expression in the brain. Here, we aimed to clarify the effects of PB on Ugt1a6 and Ugt1a7 gene expression in rat brains. Sprague Dawley rats were treated intraperitoneally with PB (80 mg/kg), once daily for 7 days. Ugt1a6 and Ugt1a7 mRNA expression levels were increased in the striatum and thalamus (Ugt1a6, 3.0- and 2.9-fold, respectively; Ugt1a7, 2.6- and 2.6-fold, respectively). Acetaminophen glucuronidation was also increased in the medulla oblongata and thalamus by 1.8- and 1.2-fold, respectively. The induction rates within different brain regions were correlated with Ugt1a6 and Ugt1a7 mRNA expression, and the degree of induction also correlated with that of NF-E2 related factor-2 mRNA. Measurement of oxidative stress markers suggested that PB induced oxidative stress in brain regions in which Ugt1a6 and Ugt1a7 mRNAs were increased. Moreover, histone modifications were altered by PB treatment, resulting in increased histone H3 lysine 4 trimethylation in the striatum and thalamus and decreased histone H3 lysine 9 trimethylation in the thalamus. These results suggested that oxidative stress and histone modifications may promote transcriptional activation of Ugt1a6 and Ugt1a7 genes. In summary, Ugt1a6 and Ugt1a7 mRNA levels were increased by PB treatment, which may alter pharmacokinetics in the brain. PMID- 26684500 TI - Telemedicine Interest for Routine Follow-Up Care Among Neurology Patients in Arkansas. AB - BACKGROUND: Teleneurology in Arkansas has been used primarily for management of acute stroke with a state-funded hub-and-spoke model allowing physicians at rural hospitals to access vascular neurologists in time to facilitate tissue plasminogen activator administration. Routine neurologic care has been provided only in small pilot studies. We wished to determine patient interest in participating in teleneurology for routine follow-up visits as well as demographic and medical factors associated with interest. MATERIALS AND METHODS: New and established patients of the Neurology Outpatient Clinic at the University of Arkansas for Medical Sciences (UAMS) were surveyed between March 2011 and December 2012 to assess their interest in participating in teleneurology as well as potential factors associated with their interest. RESULTS: Of 1,441 respondents, 52.4% were interested in telemedicine. Of those interested versus uninterested in telemedicine, respectively, 68.9% versus 36.32% traveled more than 1 h to the clinic, 64.7% versus 35.3% had difficulty secondary to neurological conditions, 22.6% versus 6.8% had missed medical appointments due to travel problems, and 43.1% versus 9.4% had travel-imposed financial hardship. CONCLUSIONS: Telemedicine interest for routine follow-up visits was strong among patients at the UAMS Neurology Outpatient Clinic. Factors positively associated with interest included long travel distances, travel expenses, and transportation difficulties. These results suggest that implementing a telemedicine program for follow-up visits would be acceptable to neurology patients for routine ongoing care. PMID- 26684501 TI - c-Fos importance for brain development. PMID- 26684502 TI - The 13th Annual Aurora Biomed Ion Channel Retreat: Three Days of Research, Technology, and Networking. AB - The 13th Annual Ion Channel Retreat was held by Aurora Biomed in Vancouver, Canada from July 7 to 9, 2015. The meeting showcased prominent current research including cardiac safety and pharmacology; ion channel structure, function and engineering; transporters and ion pumps; screening technologies; ion channels as disease targets; alcohol, tobacco, and ion channels; and ion channels as pain targets. This report summarizes the work presented at the retreat. PMID- 26684503 TI - A Strategy for Origins of Life Research. AB - Contents 1. Introduction 1.1. A workshop and this document 1.2. Framing origins of life science 1.2.1. What do we mean by the origins of life (OoL)? 1.2.2. Defining life 1.2.3. How should we characterize approaches to OoL science? 1.2.4. One path to life or many? 2. A Strategy for Origins of Life Research 2.1. Outcomes-key questions and investigations 2.1.1. Domain 1: Theory 2.1.2. Domain 2: Practice 2.1.3. Domain 3: Process 2.1.4. Domain 4: Future studies 2.2. EON Roadmap 2.3. Relationship to NASA Astrobiology Roadmap and Strategy documents and the European AstRoMap Appendix I Appendix II Supplementary Materials References. PMID- 26684504 TI - Survival of Antarctic Cryptoendolithic Fungi in Simulated Martian Conditions On Board the International Space Station. AB - Dehydrated Antarctic cryptoendolithic communities and colonies of the rock inhabitant black fungi Cryomyces antarcticus (CCFEE 515) and Cryomyces minteri (CCFEE 5187) were exposed as part of the Lichens and Fungi Experiment (LIFE) for 18 months in the European Space Agency's EXPOSE-E facility to simulated martian conditions aboard the International Space Station (ISS). Upon sample retrieval, survival was proved by testing colony-forming ability, and viability of cells (as integrity of cell membrane) was determined by the propidium monoazide (PMA) assay coupled with quantitative PCR tests. Although less than 10% of the samples exposed to simulated martian conditions were able to proliferate and form colonies, the PMA assay indicated that more than 60% of the cells and rock communities had remained intact after the "Mars exposure." Furthermore, a high stability of the DNA in the cells was demonstrated. The results contribute to assessing the stability of resistant microorganisms and biosignatures on the surface of Mars, data that are valuable information for further search-for-life experiments on Mars. KEY WORDS: Endoliths-Eukaryotes-Extremophilic microorganisms Mars-Radiation resistance. PMID- 26684505 TI - Weathering Profiles in Phosphorus-Rich Rocks at Gusev Crater, Mars, Suggest Dissolution of Phosphate Minerals into Potentially Habitable Near-Neutral Waters. AB - Abundant evidence indicates that significant surface and near-surface liquid water has existed on Mars in the past. Evaluating the potential for habitable environments on Mars requires an understanding of the chemical and physical conditions that prevailed in such aqueous environments. Among the geological features that may hold evidence of past environmental conditions on Mars are weathering profiles, such as those in the phosphorus-rich Wishstone-class rocks in Gusev Crater. The weathering profiles in these rocks indicate that a Ca phosphate mineral has been lost during past aqueous interactions. The high phosphorus content of these rocks and potential release of phosphorus during aqueous interactions also make them of astrobiological interest, as phosphorus is among the elements required for all known life. In this work, we used Mars mission data, laboratory-derived kinetic and thermodynamic data, and data from terrestrial analogues, including phosphorus-rich basalts from Idaho, to model a conceptualized Wishstone-class rock using the reactive transport code CrunchFlow. Modeling results most consistent with the weathering profiles in Wishstone-class rocks suggest a combination of chemical and physical erosion and past aqueous interactions with near-neutral waters. The modeling results also indicate that multiple Ca-phosphate minerals are likely in Wishstone-class rocks, consistent with observations of martian meteorites. These findings suggest that Gusev Crater experienced a near-neutral phosphate-bearing aqueous environment that may have been conducive to life on Mars in the past. KEY WORDS: Mars-Gusev Crater Wishstone-Reactive transport modeling-CrunchFlow-Aqueous interactions-Neutral pH Habitability. PMID- 26684506 TI - Isolation of Radiation-Resistant Bacteria from Mars Analog Antarctic Dry Valleys by Preselection, and the Correlation between Radiation and Desiccation Resistance. AB - Extreme radiation-resistant microorganisms can survive doses of ionizing radiation far greater than are present in the natural environment. Radiation resistance is believed to be an incidental adaptation to desiccation resistance, as both hazards cause similar cellular damage. Desert soils are, therefore, promising targets to prospect for new radiation-resistant strains. This is the first study to isolate radiation-resistant microbes by using gamma-ray exposure preselection from the extreme cold desert of the Antarctic Dry Valleys (a martian surface analogue). Halomonads, identified by 16S rRNA gene sequencing, were the most numerous survivors of the highest irradiation exposures. They were studied here for the first time for both their desiccation and irradiation survival characteristics. In addition, the association between desiccation and radiation resistance has not been investigated quantitatively before for a broad diversity of microorganisms. Thus, a meta-analysis of scientific literature was conducted to gather a larger data set. A strong correlation was found between desiccation and radiation resistance, indicating that an increase in the desiccation resistance of 5 days corresponds to an increase in the room-temperature irradiation survival of 1 kGy. Irradiation at -79 degrees C (representative of average martian surface temperatures) increases the microbial radiation resistance 9-fold. Consequently, the survival of the cold-, desiccation-, and radiation-resistant organisms isolated here has implications for the potential habitability of dormant or cryopreserved life on Mars. KEY WORDS: Extremophiles Halomonas sp.-Antarctica-Mars-Ionizing radiation-Cosmic rays. PMID- 26684508 TI - Length scales in glass-forming liquids and related systems: a review. AB - The central problem in the study of glass-forming liquids and other glassy systems is the understanding of the complex structural relaxation and rapid growth of relaxation times seen on approaching the glass transition. A central conceptual question is whether one can identify one or more growing length scale(s) associated with this behavior. Given the diversity of molecular glass formers and a vast body of experimental, computational and theoretical work addressing glassy behavior, a number of ideas and observations pertaining to growing length scales have been presented over the past few decades, but there is as yet no consensus view on this question. In this review, we will summarize the salient results and the state of our understanding of length scales associated with dynamical slow down. After a review of slow dynamics and the glass transition, pertinent theories of the glass transition will be summarized and a survey of ideas relating to length scales in glassy systems will be presented. A number of studies have focused on the emergence of preferred packing arrangements and discussed their role in glassy dynamics. More recently, a central object of attention has been the study of spatially correlated, heterogeneous dynamics and the associated length scale, studied in computer simulations and theoretical analysis such as inhomogeneous mode coupling theory. A number of static length scales have been proposed and studied recently, such as the mosaic length scale discussed in the random first-order transition theory and the related point-to set correlation length. We will discuss these, elaborating on key results, along with a critical appraisal of the state of the art. Finally we will discuss length scales in driven soft matter, granular fluids and amorphous solids, and give a brief description of length scales in aging systems. Possible relations of these length scales with those in glass-forming liquids will be discussed. PMID- 26684507 TI - Hydrothermal Conditions and the Origin of Cellular Life. AB - The conditions and properties of hydrothermal vents and hydrothermal fields are compared in terms of their ability to support processes related to the origin of life. The two sites can be considered as alternative hypotheses, and from this comparison we propose a series of experimental tests to distinguish between them, focusing on those that involve concentration of solutes, self-assembly of membranous compartments, and synthesis of polymers. Key Word: Hydrothermal systems. PMID- 26684509 TI - Sex-dependence of anxiety-like behavior in cannabinoid receptor 1 (Cnr1) knockout mice. AB - Epidemiological data suggest women are at increased risk for developing anxiety and depression, although the mechanisms for this sex/gender difference remain incompletely understood. Pre-clinical studies have begun to investigate sex dependent emotional learning and behavior in rodents, particularly as it relates to psychopathology; however, information about how gonadal hormones interact with the central nervous system is limited. We observe greater anxiety-like behavior in male mice with global knockout of the cannabinoid 1 receptor (Cnr1) compared to male, wild-type controls as measured by percent open arm entries on an elevated plus maze test. A similar increase in anxiety-like behavior, however, is not observed when comparing female Cnr1 knockouts to female wild-type subjects. Although, ovariectomy in female mice did not reverse this effect, both male and female adult mice with normative development were sensitive to Cnr1 antagonist mediated increases in anxiety-like behavior. Together, these data support an interaction between sex, potentially mediated by gonadal hormones, and the endocannabinoid system at an early stage of development that is critical for establishing adult anxiety-like behavior. PMID- 26684511 TI - Native Myocardial T1 as a Biomarker of Cardiac Structure in Non-Ischemic Cardiomyopathy. AB - Diffuse myocardial fibrosis is involved in the pathology of nonischemic cardiomyopathy (NIC). Recently, the application of native (noncontrast) myocardial T1 measurement has been proposed as a method for characterizing diffuse interstitial fibrosis. To determine the association of native T1 with myocardial structure and function, we prospectively studied 39 patients with NIC (defined as left ventricular ejection fraction (LVEF) <= 50% without cardiac magnetic resonance (CMR) evidence of previous infarction) and 27 subjects with normal LVEF without known overt cardiovascular disease. T1, T2, and extracellular volume fraction (ECV) were determined over 16 segments across the base, mid, and apical left ventricular (LV). NIC participants (57 +/- 15 years) were predominantly men (74%), with a mean LVEF 34 +/- 10%. Subjects with NIC had a greater native T1 (1,131 +/- 51 vs 1,069 +/- 29 ms; p <0.0001), a greater ECV (0.28 +/- 0.04 vs 0.25 +/- 0.02, p = 0.002), and a longer myocardial T2 (52 +/- 8 vs 47 +/- 5 ms; p = 0.02). After multivariate adjustment, a lower global native T1 time in NIC was associated with a greater LVEF (beta = -0.59, p = 0.0003), greater right ventricular ejection fraction (beta = -0.47, p = 0.006), and smaller left atrial volume index (beta = 0.51, p = 0.001). The regional distribution of native myocardial T1 was similar in patients with and without NIC. In NIC, native myocardial T1 is elevated in all myocardial segments, suggesting a global (not regional) abnormality of myocardial tissue composition. In conclusion, native T1 may represent a rapid, noncontrast alternative to ECV for delineating myocardial tissue remodeling in NIC. PMID- 26684512 TI - Right Ventricular Ejection Fraction in Ischemic Versus Nonischemic Cardiomyopathy. AB - The relation between the etiology of cardiomyopathy and the function of the right ventricle (RV) has not been well described in the current era of 3-dimensional cardiac imaging. New advances in cardiac imaging with computed tomography (CT) have allowed accurate measurements of ejection fraction (EF), often a challenging task considering the unique RV shape. We evaluated 130 patients at the Loma Linda Veterans Affairs Healthcare System with cardiomyopathy and a left ventricular (LV) EF <= 40%. Etiology of cardiomyopathy was determined by CT angiography as ischemic (n = 56) or nonischemic (n = 74). RV volumes and RVEF were calculated based on 3-dimensional data set from CT images. Baseline LVEF was similar with a mean LVEF of 28% (+/- 6%) in the ischemic group and 28% (+/- 9%) in the nonischemic group (p = 0.46). RV function and volumes were moderately decreased in both cohorts, without significant difference between the groups (mean RVEF 34 +/- 11% in ischemic group and 32 +/- 10% in nonischemic group, p = 0.26). In conclusion, most patients with LV dysfunction also have RV dysfunction. The degree of RV dysfunction is not dependent on the etiology of cardiomyopathy. PMID- 26684510 TI - Decreased daytime illumination leads to anxiety-like behaviors and HPA axis dysregulation in the diurnal grass rat (Arvicanthis niloticus). AB - The impact of ambient light on mood and anxiety is best exemplified in seasonal affective disorder, in which patients experience depression and anxiety in winter when there is less light in the environment. However, the brain mechanisms underlying light-dependent changes in affective state remain unclear. Our previous work revealed increased depression-like behaviors in the diurnal Nile grass rat (Arvicanthis niloticus) housed in a dim light-dark (dim-LD) cycle as compared to the controls housed in a bright light-dark (bright-LD) condition. As depression is often comorbid with anxiety and is associated with dysregulation of the body's stress response system, the present study examined the anxiety-like behaviors as well as indicators of the hypothalamic-pituitary-adrenal (HPA) axis functioning in the grass rats. Animals housed in dim-LD showed increased anxiety like behaviors compared to bright-LD controls, as revealed by fewer entries and less time spent at the center in the open field test and more marbles buried during the marble-burying test. Following the marble-burying test, dim-LD animals showed higher plasma corticosterone (CORT) levels and hippocampal Fos expression. Although the daily CORT rhythm was comparable between bright-LD and dim-LD groups, the day/night variation of corticotropin-releasing hormone mRNA expression in the paraventricular nucleus was diminished in dim-LD animals. In addition, glucocorticoid receptor and mineralocorticoid receptor mRNA expression were higher in the hippocampus of dim-LD animals. The results suggest that in diurnal species, reduced daytime illumination can lead to increased anxiety-like behaviors and altered HPA axis functioning, providing insights into the link between decreased environmental illumination and negative emotion. PMID- 26684513 TI - Comparative Assessment of Mitral Regurgitation Severity by Transthoracic Echocardiography and Cardiac Magnetic Resonance Using an Integrative and Quantitative Approach. AB - Although transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) are validated in quantitation of mitral regurgitation (MR), discrepancies may occur. This study assesses the agreement between TTE and CMR in MR and evaluates characteristics and clinical outcome of patients with discrepancy. From our institutional database, 70 subjects with MR underwent both TTE and CMR within 30 days (median 3 days). MR was evaluated semiquantitatively (n = 70) using a 4 grade scale and quantitatively (n = 60) with calculation of regurgitant volume (RVol) and regurgitant fraction (RF). Of the 70 subjects, qualitative assessment by TTE yielded 30 subjects with mild MR, 17 moderate, and 23 moderately severe or severe MR. Exact concordance in MR grade was seen in 50% and increased to 91% when considering concordance within one grade of severity (kappa = 0.44). A modest correlation was observed for RVol and RF between both methods (r = 0.59 and 0.54, respectively, p <0.0001). Ten patients had a significant discrepancy in quantitative MR (difference in RF >20%); the frequency of secondary MR was higher (100% vs 46%; p = 0.003) in patients with discrepancy. Although interobserver variability in RF was higher with TTE compared with CMR (-5.5 +/- 15% vs 0.1 +/- 7.3%), patients with discrepancy were equally distributed by severity and clinical outcome without an overestimation by either method. In conclusion, there is a modest agreement between TTE and CMR in assessing MR severity. In patients with discrepancy, there is a higher prevalence of functional MR, without a consistent overestimation of MR severity by either method. PMID- 26684514 TI - Takotsubo Syndrome and Acute Myocardial Infarction: Causal Links. PMID- 26684515 TI - Predictive Value of Combining the Ankle-Brachial Index and SYNTAX Score for the Prediction of Outcome After Percutaneous Coronary Intervention (from the SHINANO Registry). AB - The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI <= 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score <= 22 was defined as 0, 23 to 32 as 1, and >= 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone. PMID- 26684517 TI - Estimating the Sensitivity of Holter to Detect Atrial Fibrillation After Stroke or Transient Ischemic Attack Without a Gold Standard is Challenging. PMID- 26684516 TI - A Simple and Portable Algorithm for Identifying Atrial Fibrillation in the Electronic Medical Record. AB - Atrial fibrillation (AF) is common and increases stroke risk and mortality. Many knowledge gaps remain with respect to practice patterns and outcomes. Electronic medical records (EMRs) may serve as powerful research tools if AF status can be properly ascertained. We sought to develop an algorithm for identifying subjects with and without AF in the EMR and compare it to previous methods. Using a hospital network EMR (n = 5,737,846), we randomly selected 8,200 subjects seen at a large academic medical center in January 2014 to derive and validate 7 AF classification schemas (4 cases and 3 controls) to construct a composite AF algorithm. In an independent sample of 172,138 subjects, we compared this algorithm against published AF classification methods. In total, we performed manual adjudication of AF in 700 subjects. Three AF schemas (AF1, AF2, and AF4) achieved positive predictive value (PPV) >0.9. Two control schemas achieved PPV >0.9 (control 1 and control 3). A combination algorithm AF1, AF2, and AF4 (PPV 88%; 8.2% classified) outperformed published classification methods including >1 outpatient International Statistical Classification of Diseases, Ninth Revision code or 1 outpatient code with an electrocardiogram demonstrating AF (PPV 82%; 5.9% classified), >= 1 inpatient International Statistical Classification of Diseases, Ninth Revision code or electrocardiogram demonstrating AF (PPV 88%; 6.1% classified), or the intersection of these (PPV 84%; 7.4% classified). When applied simultaneously, the case and control algorithms classified 98.4% of the cohort with zero disagreement. In conclusion, we derived a parsimonious and portable algorithm to identify subjects with and without AF with high sensitivity. If broadly applied, this algorithm can provide optimal power for EMR based AF research. PMID- 26684518 TI - Heparin-Induced Thrombocytopenia in Contemporary Cardiac Surgical Practice and Experience With a Protocol for Early Identification. AB - This analysis was designed to (1) examine the impact of heparin-induced thrombocytopenia (HIT) on contemporary cardiac surgical practice and (2) describe the results of a protocol designed for early identification of the presence of the immune mechanisms involved. Consecutive patients who underwent cardiac surgery were screened postoperatively for thrombocytopenia. Patients with thrombocytopenia were tested for antiplatelet factor 4 (PF4)/heparin antibodies by ELISA and clinical evidence of thrombosis sought. Demographics, co morbidities, operative details, and outcomes were abstracted from the departmental registry. Of 14,415 consecutive patients undergoing cardiac surgery, 1,849 patients (13%) had thrombocytopenia. Of them, 277 patients (15%) had PF4/heparin antibodies and 76 patients (4%) had both antibodies and clinical thrombosis. Antibodies were more frequent: (1) in women (p = 0.01), (2) in patients with an increased body mass index (p <0.01), and (3) in patients with clinical heart failure before surgery (p <0.01). Thirty-day mortality was greatest among the 76 patients with the triad of thrombocytopenia, antibodies, and clinical thrombosis (30%). Of the 1,849 patients with thrombocytopenia, the presence of PF4/heparin antibodies was an independent predictor of 30-day mortality (odds ratio 2.09, 95% CI 1.46 to 2.49; p <0.001). HIT remains an infrequent but very serious complication of heparin therapy in contemporary cardiac surgical practice. The possibility that the presence of HIT antibodies in patients with thrombocytopenia independently increases operative mortality deserves further study. PMID- 26684519 TI - Design of Surface-Active Artificial Enzyme Particles to Stabilize Pickering Emulsions for High-Performance Biphasic Biocatalysis. AB - Surface-active artificial enzymes (SAEs) are designed and constructed by a general and novel strategy. These SAEs can simultaneously stabilize Pickering emulsions and catalyze biphasic biotransformation with superior enzymatic stability and good re-usability; for example, for the interfacial conversion of hydrophobic p-nitrophenyl butyrate into yellow water-soluble p-nitrophenolate catalyzed by esterase-mimic SAE. PMID- 26684523 TI - Crimean-Congo Hemorrhagic Fever Virus Subunit Vaccines Induce High Levels of Neutralizing Antibodies But No Protection in STAT1 Knockout Mice. AB - Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus of the Nairovirus genus that causes hemorrhagic fever in humans with high case fatality. Here, we report the development of subunit vaccines and their efficacy in signal transducer and activator of transcription 1 (STAT1) knockout mice. Ectodomains of the structural glycoproteins Gn and Gc were produced using a Drosophila insect cell-based expression system. A single vaccination of STAT129 mice with adjuvanted Gn or Gc ectodomains induced neutralizing antibody responses, which were boosted by a second vaccination. Despite these antibody responses, mice were not protected from a CCHFV challenge infection. These results suggest that neutralizing antibodies against CCHFV do not correlate with protection of STAT1 knockout mice. PMID- 26684524 TI - Environmental Factors and Ecosystems Associated with Canine Visceral Leishmaniasis in Northeastern Brazil. AB - Environment influences the composition, distribution, and behavior of the vectors and mammalian hosts involved in the transmission of visceral leishmaniasis (VL), affecting the epidemiology of the disease. In Brazil, the urbanization process and canine cases of VL are indicators for local health authorities. This study aimed to investigate the occurrence of the canine visceral leishmaniasis (CVL) in Maranhao State, Brazil. Blood samples collected from 960 dogs from six municipalities and six different ecosystems (Baixada Maranhense, Mangue, Mata dos Cocais, Amazonia, Cerrado, and Restinga) to serological tests (enzyme-linked immunosorbent assay [ELISA], indirect fluorescence antibody test [IFAT], and chromatographic immunoassay methods [Dual Path Platform technology, DPP((r))]) and parasitological diagnosis. From serological tests, 11.14% (107) of the dogs were positive for CVL, with 59.16% (568), 14.5% (148), and 131% (126) positives to ELISA, DPP, and IFAT tests, respectively. Only seven animals (0.73%) were positive in a parasitological test. We also performed parasite isolation and phylogenetic characterization. All isolates of dogs obtained from Maranhao were grouped in a single branch with Leishmania infantum chagasi from Brazil. The ecosystem Amazonia presented the highest positivity rates to CVL in serological and parasitological tests. Brazilian biomes/ecosystems suffer large degradation and may favor, depending on climatic conditions, the installation of new diseases. In the case of VL, dogs are reservoirs of parasites and sentinels for human infection. PMID- 26684525 TI - First report of Toxoplasma gondii Seroprevalence in Farmed Arctic Foxes (Vulpes lagopus) in Eastern and Northeastern China. AB - Until now, no information on Toxoplasma gondii seroprevalence in Arctic foxes (Vulpes lagopus) was available in China. A serological survey was undertaken to assess T. gondii seroprevalence in farmed Arctic foxes in eastern and northeastern China. Antibodies to T. gondii were examined in 1346 farmed Arctic foxes using the modified agglutination test (MAT). A total of 113 (8.39%, 95% confidence interval [CI] 6.91-9.87) serum samples were positive to T. gondii at a 1:25 cutoff. Seroprevalence of T. gondii infection in male Arctic foxes was 8.68% (95% CI 6.75-10.6), which was higher than that in the female Arctic foxes (7.95%, 95% CI 5.65-10.26). The prevalence in polar foxes was 7.07% (95% CI 5.14-8.99), which was lower than that in the blue foxes (9.75%, 95% CI 7.49-11.99). T. gondii seroprevalence in Arctic foxes in Heilongjiang, Jilin, Liaoning, and Shandong Provinces was 9.85% (95% CI 5.75-13.95), 9.21% (95% CI 5.54-12.87), 7.37% (95% CI 5.22-9.51), and 8.68% (95% CI 5.66-11.70), respectively. There were no statistically significant differences between T. gondii seroprevalence and morphs, sex, or regions of Arctic foxes in logistic regression analysis (p < 0.05). The results of the present survey indicated that T. gondii infection in farmed Arctic foxes is prevalent in China. To our knowledge, this is the first report of T. gondii seroprevalence in Arctic foxes in China. PMID- 26684527 TI - Time to abandon awake fibreoptic intubation? PMID- 26684526 TI - Investigations on Rickettsia in Ticks at the Sino-Russian and Sino-Mongolian Borders, China. AB - To describe the prevalence of Rickettsia in ticks at the Sino-Russian and Sino Mongolian borders, a total of 292 ticks were collected and tested by conventional PCR assays. The prevalence of Rickettsia was 53.4%, and phylogenetic analysis showed that they belonged to R. raoultii species after alignment for the ompA, ompB, and gltA genes, respectively. Coxiella burnetii DNA was detected for 14%, and no Ehrlichia, Borrelia burgdorferi, and Babesia species were found. Co infection of two pathogens was 9.9%, and no co-infection with three or more pathogens was found. This study suggested Rickettsia was the most common pathogen in the ticks and co-infection was found. The findings might be helpful to provide advice on the prevention and control of tick-borne disease potential for tourists and residents. PMID- 26684528 TI - CCTIVA and NAP5. PMID- 26684529 TI - Righting the wrongs of traditional medical hierarchy. PMID- 26684530 TI - Hierarchy in critical airway management. PMID- 26684531 TI - Intercostal/paraspinal nerve block for thoracic surgery. PMID- 26684532 TI - Nerve block injection pressure monitoring. PMID- 26684533 TI - Succinylcholine and neuromuscular blockade monitoring. PMID- 26684534 TI - Sugammadex - time of onset: nine months. PMID- 26684535 TI - Yet another failure of a prefilled glass syringe. PMID- 26684536 TI - We read Dr. Goodman's letter with interest .... PMID- 26684537 TI - Would you post a comment if you weren't interested? PMID- 26684538 TI - Bacterial ferrous iron transport: the Feo system. AB - To maintain iron homeostasis within the cell, bacteria have evolved various types of iron acquisition systems. Ferric iron (Fe(3+)) is the dominant species in an oxygenated environment, while ferrous iron (Fe(2+)) is more abundant under anaerobic conditions or at low pH. For organisms that must combat oxygen limitation for their everyday survival, pathways for the uptake of ferrous iron are essential. Several bacterial ferrous iron transport systems have been described; however, only the Feo system appears to be widely distributed and is exclusively dedicated to the transport of iron. In recent years, many studies have explored the role of the FeoB and FeoA proteins in ferrous iron transport and their contribution toward bacterial virulence. The three-dimensional structures for the Feo proteins have recently been determined and provide insight into the molecular details of the transport system. A highly select group of bacteria also express the FeoC protein from the same operon. This review will provide a comprehensive look at the structural and functional aspects of the Feo system. In addition, bioinformatics analyses of the feo operon and the Feo proteins have been performed to complement our understanding of this ubiquitous bacterial uptake system, providing a new outlook for future studies. PMID- 26684539 TI - Editorial: The many wonders of the bacterial cell surface. PMID- 26684540 TI - Extracorporeal Life Support in Out-of-Hospital Refractory Cardiac Arrest. AB - Out-of-Hospital refractory Cardiac Arrest (OHrCA) has a mortality rate between 90 and 95%. Since 2009, French medical academic societies have recommended the use of extracorporeal life support (ECLS) for OHrCA. According to these guidelines, patients were eligible for ECLS support if vital signs were still present during cardiopulmonary resuscitation (CPR), or if cardiac arrest was secondary to intoxication or hypothermia (<=32 degrees C). Otherwise, patients would receive ECLS if (i) no-flow duration was less than 5 min; (ii) time delays from CPR to ECLS start (low flow) were less than 100 min; and (iii) expiratory end tidal CO2 (ETCO2 ) was more than 10 mm Hg 20 min after initiating CPR. We have reported here our experience with ECLS in OHrCA according to the previous guidelines. We retrospectively analyzed mortality rates of patients supported with ECLS in case of OHrCA. From December 2009 to December 2013, 183 patients were assisted with ECLS, among which 32 cases were of OHrCA. Mean age for the OHrCA patients was 43.6 years. Over two-thirds were male (71.9%). Causes of OHrCA included intoxication, isolated hypothermia <32 degrees C, acute coronary syndrome, pulmonary edema, and other cardiac pathology. Despite adherence to protocols, only two patients (6.2%) with hypothermia and acute myocardium ischemia, respectively, could be discharged from hospital after cardiac recovery. Causes of death were brain death and multiple organ failure. Despite ECLS support setting in accordance with French guidelines in case of refractory OHrCA, mortality rates remained high. French ECLS support recommendations for OHrCA due to presumed cardiac cause should be re-examined through new studies. Low flow duration should be improved by a shorter time of CPR before hospital transfer. PMID- 26684541 TI - Sociodemographic Differences by Survey Mode in a Respondent-Driven Sampling Study of Transgender People in Ontario, Canada. AB - PURPOSE: To describe survey mode uptake and sociodemographic differences by mode among respondents to a respondent-driven sampling survey of transgender people in Ontario, Canada. Survey mode was left to participant choice. METHODS: Data were collected from 433 transgender Ontarians in 2009-2010 through a self-administered questionnaire, available online, by paper copy, or by telephone with language interpretation. RESULTS: Paper respondents (9.5%) were significantly more likely to be Aboriginal or persons of color, underhoused, sex workers, and unemployed or receiving disability benefits. CONCLUSION: In Canada and similar high-income countries, sampling transgender populations that are diverse with respect to social determinants of health may be best carried out with multimode surveys. PMID- 26684542 TI - Oral microbiome, periodontitis and risk of head and neck cancer. AB - A wide range of studies has been successfully exploring the association between the human microenvironment, sustained inflammation, and cancer. Growing evidence has then emerged in this field over the past few years. Nevertheless, reliable data addressing the impact of the oral microbiome and periodontitis on the pathogenesis and risk of head and neck malignancies remain scarce. Hence, this communication focuses on briefly discuss the relationship between the oral microbiome, periodontitis and head and neck cancer based on the current understanding of such a disease-associated scenario. PMID- 26684543 TI - Discordance in routine second opinion pathology review of head and neck oncology specimens: A single-center five year retrospective review. AB - OBJECTIVES: Second opinion review of pathology specimens is a common institutional practice, supported by large retrospective studies demonstrating significant histologic discordance. Since the most recent study of head and neck specific pathology review was conducted, routine HPV and EBV testing is now recommended for certain specimens. We describe the frequency of and reasons for discordant reports and their potential impact on treatment recommendations and prognosis in a five-year retrospective cohort study at a single academic referral institution from 2005 to 2010. MATERIALS AND METHODS: Following institutional review board review, 1003 cases referred to the Head and Neck Oncology Service were identified using a retrospective database search. Discordance between outside and second review pathology report was assessed by a board-certified medical oncologist. RESULTS: 667 cases were included, of which 22% were discordant. Discordance was associated with adenocarcinomas (AOR [adjusted odds ratio] 0.09, 95% CI 0.03-0.31; p<0.001), poorly differentiated carcinomas (AOR 0.14, 95% CI 0.06-0.39; p<0.001), and specimens of uncommon histology (AOR 0.18, 95% CI 0.07-0.45; p<0.001) but not biopsy site in a multivariate model. The most common reasons for discordance included histology (61%), followed by the results of special studies (36%), and the presence or absence of stromal invasion (14%). Differences in tumor HPV status comprised 16% of discordant cases and were associated with better prognosis (p<0.001) following second opinion review. CONCLUSIONS: Routine second opinion pathology review may lead to clinically significant differences in treatment recommendations and prognosis. PMID- 26684544 TI - Supportive care needs of oral cancer survivors: Prevalence and correlates. AB - OBJECTIVES: Many cancer survivors experience unmet supportive care needs. The oral cancer survivor population is growing; however, little is known about the unique needs of this group. The present study aimed to determine the supportive care needs of persons with oral cancer who had completed active treatment at least three months previously. MATERIALS AND METHODS: Oral cancer survivors (N=342) completed an online questionnaire that included the validated Survivors Unmet Needs Survey (SUNS). Relationships between SUNS subscales and various demographic, clinical, and psychosocial variables were examined in univariate and multivariate analyses. Survivors also indicated their top unmet needs and interest in supportive care services. RESULTS: Survivors reported substantial unmet needs across all domains, with many of the top unmet needs falling in the emotional domain. Poorer mental and physical health were associated with greater unmet needs across all domains. In each domain, select demographic and clinical variables also were associated with greater unmet needs in univariate and multivariate analyses. Survivors reported high rates of interest in several supportive care services including support groups and various forms of informational support. CONCLUSION: The present study highlights the significant burden of unmet supportive care needs in oral cancer survivors who have completed treatment and are coping with long-term ramifications of the disease and its treatment, reveals factors related to those needs, outlines these survivors' interest in a range of supportive care services, and suggests future research directions. PMID- 26684546 TI - Characterization of physiological phenotypes of dentate gyrus synapses of PDZ1/2 domain-deficient PSD-95-knockin mice. AB - The hippocampal formation is involved in several important brain functions of animals, such as memory formation and pattern separation, and the synapses in the dentate gyrus (DG) play critical roles as the first step in the hippocampal circuit. Previous studies have reported that mice with genetic modifications of the PDZ1/2 domains of postsynaptic density (PSD)-95 exhibit altered synaptic properties in the DG and impaired hippocampus-dependent behaviors. Based on the involvement of the DG in the regulation of behaviors, these data suggest that the abnormal behavior of these knockin (KI) mice is due partly to altered DG function. Precise understanding of the phenotypes of these mutant mice requires characterization of the synaptic properties of the DG, and here we provide detailed studies of DG synapses. We have demonstrated global changes in the PSD membrane-associated guanylate kinase expression pattern in the DG of mutant mice, and DG synapses in these mice exhibited increased long-term potentiation under a wide range of stimulus intensities, although the N-methyl-d-aspartic acid receptor dependence of the long-term potentiation was unchanged. Furthermore, our data also indicate increased silent synapses in the DG of the KI mice. These findings suggest that abnormal protein expression and physiological properties disrupt the function of DG neurons in these KI mice. PMID- 26684545 TI - Clinical features and prognostic factors in solitary plasmacytoma. AB - This study aimed to review the clinical features and outcome of 53 patients with solitary plasmacytoma managed at our Institution between 1976 and 2012. Thirty five patients had bone solitary plasmacytoma and 18 extramedullary solitary plasmacytoma. Tumour sizes were larger in patients with bone involvement (P = 0.003). Treatment consisted of local radiotherapy (n = 26), radiotherapy + chemotherapy (n = 15), surgery (n = 4) and chemotherapy (n = 8); the local control rate was 94.3%. Progression to multiple myeloma was recorded in 20/35 (57.1%) patients with bone involvement and in 1/18 (5.5%) patients with extramedullary disease (P = 0.0003). The 5-year overall survival (OS) rate was 78.4%; bone solitary plasmacytoma patients had a significantly worse OS (71.9% vs. 88.2%, respectively; P = 0.029) and 5-year progression-free survival (PFS; 53.0% vs. 88.5%; P = 0.0003) compared to extramedullary solitary plasmacytoma patients. On univariate analysis, bone disease and size (>=5 cm) impacted negatively on PFS (P = 0.0027 and P = 0.04, respectively). Bone disease also affected OS (P = 0.04). In multivariate analysis bone location was the only independent prognostic factor for PFS (P = 0.0041) and OS (P = 0.021). Patients with bone solitary plasmacytoma have a significantly worse prognosis than extramedullary solitary plasmacytoma cases. PMID- 26684547 TI - Carbapenem-resistant Acinetobacter baumannii acquired before liver transplantation: Impact on recipient outcomes. AB - Infection with carbapenem-resistant Acinetobacter baumannii (CRAB) after liver transplantation (LT) is associated with high mortality. This study aimed to identify risk factors for post-LT CRAB infection, as well as to evaluate the impact of pre-LT CRAB acquisition on the incidence of post-LT CRAB infection. This was a prospective cohort study of all patients undergoing LT at our facility between October 2009 and October 2011. Surveillance cultures (SCs) were collected immediately before LT and weekly thereafter, until discharge. We analyzed 196 patients who were submitted to 222 LTs. CRAB was identified in 105 (53.6%); 24 (22.9%) of these patients were found to have acquired CRAB before LT, and 85 (81.0%) tested positive on SCs. Post-LT CRAB infection occurred in 56 (28.6%), the most common site being the surgical wound. Multivariate analysis showed that the risk factors for developing CRAB infection were prolonged cold ischemia, post LT dialysis, LT due to fulminant hepatitis, and pre-LT CRAB acquisition with pre LT CRAB acquisition showing a considerable trend toward significance (P = 0.06). Among the recipients with CRAB infection, 60-day mortality was 46.4%, significantly higher than among those without (P < 0.001). Mortality risk factors were post-LT infection with multidrug-resistant bacteria, LT performed because of fulminant hepatitis, retransplantation, prolonged cold ischemia, longer LT surgical time, and pre-LT CRAB acquisition, the last showing a trend toward significance (P = 0.08). In conclusion, pre-LT CRAB acquisition appears to increase the risk of post-LT CRAB infection, which has a negative impact on recipient survival. Liver Transplantation 22 615-626 2016 AASLD. PMID- 26684548 TI - Acute respiratory failure after drowning: a retrospective multicenter survey. AB - OBJECTIVES: Despite the extensive literature on drowning, clinical data are still lacking on the best medical strategy to use. Acute respiratory failure (ARF) is the main component of drowning pathophysiology. The objectives of this multicenter study were to analyze the clinical course of drowning-related ARF patients and to describe the efficacy of the ventilatory strategies used. METHODS: Medical records of drowned adult patients admitted in seven ICUs after prehospital emergency medical care during three consecutive summer periods were retrospectively analyzed. RESULTS: Among the 126 patients (58+/-21 years) admitted, 38 patients with cardiac arrest at the scene were not analyzed, 26 received mechanical ventilation (MV), and 48 patients received noninvasive ventilation (NIV). Compared with patients placed under MV, the NIV patients presented a better initial neurological (Glasgow Coma Scale of 7+/-4 vs. 12+/-3, P<0.05) and hemodynamic status from the prehospital stage (mean arterial pressure of 77+/-18 vs. 96+/-18, P<0.001). With comparable ARF-related hypoxemia to MV, the NIV was maintained with success in 92% (44/48). Both MV and NIV were associated with rapid improvement of oxygenation and short ICU length of stay [3 (1-14) and 2 (1-7), respectively]. CONCLUSION: Despite the absence of recommendation for NIV use in case of drowning-related ARF, this technique was often used with safety and efficacy. The decision for NIV use was mainly based on the preserved or improved neurological status. PMID- 26684549 TI - Two-Dimensional Aggregation and Semidilute Ordering in Cellulose Nanocrystals. AB - The structural properties and aggregation behavior of carboxymethylated cellulose nanocrystals (CNC-COOH) were analyzed with small angle neutron scattering (SANS), transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS) and compared to sulfuric acid hydrolyzed cellulose nanocrystals (CNC-SO3H). The CNC-COOH system, prepared from single carboxymethylated cellulose nanofibrils, was shown to laterally aggregate into 2D stacks that were stable both in bulk solution and when adsorbed to surfaces. CNC SO3H also showed a 2D aggregate structure with similar cross sectional dimensions (a width to height ratio of 8) as CNC-COOH, but a factor of 2 shorter length. SANS and DLS revealed a reversible ordering of the 2D aggregates under semidilute conditions, and a structure peak was observed for both systems. This indicates an early stage of liquid crystalline arrangement of the crystal aggregates, at concentrations below those assessed using birefringence or polarized optical microscopy. PMID- 26684551 TI - A New Approach to Health Services and Pharmacy in Cuba. AB - In December 17, 2014, U.S. President Barack Obama surprised the world by announcing his intention to enter into negotiations aimed at reestablishing diplomatic relations with Cuba. Since then, expectations and interest regarding the health system of that country have increased. This report focuses on the Cuban health and pharmacy systems from a practical and educational standpoint. Pharmaceutical services, strengths, opportunities, and challenges are described. Cuba's new trends toward patient-centered care are analyzed to provide insights for developing pharmaceutical care practice and implementing policies suitable for practice in all health care settings. PMID- 26684552 TI - Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing. AB - STUDY OBJECTIVE: To compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing. DESIGN: Single-center retrospective cohort study. SETTING: Two outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson. PATIENTS: A total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between groups, except for chronic kidney disease (p<0.001), congestive heart failure (p=0.041), and mean age (p=0.004). The primary outcome was the occurrence of adverse effects arrhythmia, chest pain or tightness, dizziness, dyspnea, flushing, or headache, and use of the rescue agent aminophylline-in the adenosine and regadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, p<0.001). The patients given regadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, p<0.001), dyspnea (66.0% vs 17.7%, p<0.001), and headache (25.1% vs 3.1%, p<0.001), and they had a significantly higher rate of aminophylline rescue use (19.2% vs 0.8%, p<0.001). A secondary objective evaluated the financial impact of each agent, and adenosine exhibited a medication price that was more than $100/patient lower than regadenoson based on the average wholesale price. CONCLUSION: Among patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson. PMID- 26684553 TI - Pharmacotherapy Considerations in the Management of Transgender Patients: A Brief Review. AB - Transgender and transsexual individuals have unique health care needs and risks compared with the population at large. It is estimated that 1 in 100,000 individuals in the United States is a transgender woman and 1 in 400,000 is a transgender man, although these estimates of prevalence are likely conservative. Transgender individuals are at an increased risk of tobacco, alcohol, and substance abuse; they have an increased lifetime suicide attempt risk; and they are more likely to experience significant stressors in their lives. Transgender patients may elect to transition their appearance to the gender with which they identify. Hormone treatment (and possibly sex reassignment surgery) is a significant part of this transition, and pharmacists must understand the pharmacotherapeutic principles involved so they can better recommend therapeutic agents, provide dosing recommendations, and anticipate and manage adverse effects. It is critical to be culturally sensitive when providing care for transgender patients including using their preferred gender identity, preferred names, and preferred pronouns. It is also essential to be able to identify transgender and transsexual patients correctly within electronic health records to ensure that appropriate care and monitoring are provided. For pharmacists, this means they should know the biologic sex for performing calculations such as creatinine clearance and to prevent teratogenic agents from reaching a transgender or transsexual man who could be pregnant or is capable of becoming pregnant. Promoting knowledge of transgender health issues will enable pharmacists to provide better, more holistic care to their transgender patients. PMID- 26684554 TI - Antiretroviral Treatment Efficacy and Safety in Older HIV-Infected Adults. AB - Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV-infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50 yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV-infected patients aged 50 years and older appear to be at greater risk for certain ART-associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged 50 years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24 weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials. PMID- 26684555 TI - The Role of Statin Therapy in Hemorrhagic Stroke. AB - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely utilized class of cholesterol-lowering agents, carrying multiple indications for both primary and secondary cardiovascular risk reduction. Concern was raised by previously published post hoc analyses and observational studies that noted an increased risk of hemorrhagic stroke in patients receiving a statin. Subsequent studies have demonstrated conflicting results regarding the role of statin therapy on hemorrhagic stroke risk and patient outcomes. New evidence suggests that statins taken prior to or continued during admission for intracerebral hemorrhage (ICH) may be associated with positive outcomes. Evidence also suggests deleterious outcomes resulting from the abrupt discontinuation of statins upon hospital admission for multiple disease states including ICH. Conflicting data also exist for the use of statins following aneurysmal subarachnoid hemorrhage (aSAH). Recent evidence suggests statins started during admission for aSAH confer no additional benefit in reducing delayed ischemic neurologic deficits despite initial positive results. Larger scale evaluation of the role of statin therapy following hemorrhagic stroke is warranted. The available literature is reviewed to provide guidance for therapeutic decision making. PMID- 26684556 TI - Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug. AB - Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by unexplained left ventricular hypertrophy in the absence of other cardiac or systemic etiologies. Approximately two-thirds of patients with HCM develop left ventricular outflow tract (LVOT) obstruction with or without provocation, whereas nearly half develop heart failure with preserved ejection fraction. Medical management of heart failure with preserved ejection fraction is based on the presence of symptoms and LVOT obstruction and frequently includes beta-blockers or verapamil. Disopyramide is a class Ia antiarrhythmic that historically was used for the treatment of arrhythmias; however, its contemporary use is often reserved for patients with HCM who are persistently symptomatic despite beta blockers or verapamil and have evidence of LVOT obstruction. The pharmacologic rationale for use of disopyramide is largely based on its strong negative inotropic property. Three clinical studies have showed significant improvements in heart failure symptoms and a reduction in the need for invasive therapy in patients treated with disopyramide. Appropriate dosing and monitoring of disopyramide are important to mitigate the potential for anticholinergic adverse events and proarrhythmias. Disopyramide is a safe and effective medication that reduces heart failure symptoms and LVOT gradient and delays the need for invasive therapy in patients with obstructive HCM. PMID- 26684558 TI - Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies. AB - Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management. PMID- 26684559 TI - Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy. PMID- 26684557 TI - Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat. AB - Multiple myeloma is a neoplastic plasma cell disorder that is characterized by clonal proliferation of plasma cells in the bone marrow, monoclonal protein in the blood and/or urine, and associated organ dysfunction and biomarkers. There have been multiple recent advances in the relapsed and refractory setting. Major steps forward include the introduction of proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide) in various combinations. These drugs have changed the management of multiple myeloma and have extended overall survival in the past decade. Established curative therapy is not yet available for patients diagnosed with multiple myeloma, supporting the development of new treatment targets. Histone deacetylase inhibitors have multiple proposed mechanisms of action in the treatment of multiple myeloma. Both vorinostat and panobinostat have demonstrated some activity against multiple myeloma, and due to the benefits reported with panobinostat, the U.S. Food and Drug Administration has recently approved the drug for the treatment of relapsed and refractory multiple myeloma. In this article, we describe the pharmacology, efficacy, and toxicity profile of vorinostat and panobinostat and their possible place in therapy. PMID- 26684561 TI - Recent Innovations on Biomedical Engineering. PMID- 26684560 TI - Rapid-Onset Thrombocytopenia Following Piperacillin-Tazobactam Reexposure. AB - Drug-induced thrombocytopenia is a rare but serious adverse event that has been associated with multiple drugs including beta-lactams. Although it mostly occurs with prolonged medication use, some cases of rapid-onset thrombocytopenia have been reported. We describe the case of a 69-year-old man who developed severe and immediate thrombocytopenia following reexposure to piperacillin-tazobactam in the critical care setting. He received a 6-day course of piperacillin-tazobactam for a possible pneumonia immediately after cardiac surgery. During this course of therapy, his platelet count decreased (fluctuating between 69 * 10(3) /mm(3) and 104 * 10(3) /mm(3) ) and then progressively increased after completion of the antibiotic to 340 * 10(3) /mm(3) on postoperative day 15. Ten days after the antibiotic course was completed (postoperative day 16), the patient developed new signs of infection (fever and neutrophilia), and piperacillin-tazobactam was restarted. Eight hours after reintroducing the antibiotic, his platelet count dropped from 317 * 10(3) /mm(3) to 7 * 10(3) /mm(3) . After reviewing all the medications administered to the patient as well as other potential causes of thrombocytopenia, and given the chronology of events, piperacillin-tazobactam was suspected as the most likely offending agent and was therefore replaced by meropenem on postoperative day 17. The patient's platelet count began to rise 2 days after discontinuation of piperacillin-tazobactam and reached 245 * 10(3) /mm(3) by postoperative day 30. No spontaneous bleeding or thrombosis occurred while the patient was thrombocytopenic. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of thrombocytopenia and piperacillin-tazobactam therapy. This case highlights the severity and swiftness in which drug-induced thrombocytopenia may present in the context of cardiac surgery. PMID- 26684562 TI - Analysis of epidermal/dermal temperature changes according to the different cryogen spray cooling conditions. AB - This study measured epidermal and dermal temperatures under different cryogen spray cooling (CSC) conditions to determine the optimum cooling conditions for skin rejuvenation. For this purpose, CSC conditions were applied before a laser transmission for varying spurt times of 50, 150, and 200 ms with delay times of 150 and 200 ms. A long-pulsed 1,064 nm Nd:YAG laser irradiated the skin surface of a pig with a condition of fluence of 26 J/cm2 and a spot diameter of 8 mm. The pulse duration was set to 30 ms during all experiments. This study found that all employed CSC conditions significantly decreased internal-external skin temperatures. Moreover, skin temperatures were influenced more by variations in spurt time of CSC compared with the delay times. Based on these experimental results, two spurt times were selected as the optimum CSC conditions for skin rejuvenation: 50 ms with delay time of 150 and 200 ms and 150 ms with a delay time of 150 and 200 ms. PMID- 26684563 TI - G2/M arrest and apoptosis of human colorectal cancer cells induced by water extract from residues of jelly fig achene. AB - Jelly fig (Ficus awkeotsang) achenes have been utilized to prepare a traditional drink in Taiwan. Herein, we evaluated the effect of water extract from jelly fig seed residues (WERJFA) on cancer cells. WERJFA could inhibit the growth of human colorectal cancer cells, COLO205 and HT29 in both dose- and time-dependent manners. The flow cytometric analysis with propidium iodide (PI) showed that WERJFA primarily arrested COLO205 and HT29 cells at the G2/M phase of cell cycle as the concentration reached to at least 0.5 mg/ml. WERJFA induced apoptosis of these two cell lines, as evidenced by annexin V-FITC/PI and 4', 6-diamidino-2 phenylindole (DAPI) staining using flow cytometry and confocal microscopy, respectively. Reactive oxygen species (ROS) production and the loss of mitochondrial membrane potential in WERJFA-treated cells were detected by flow cytometry with H2DCF-DA and 5,5', 6,6'-Tetrachloro-1, 1', 3,3' tetraethylbenzimidazolocarbocyanine iodide (JC-1). Our results showed that WERJFA exerted anti-proliferative and apoptotic effects on colorectal cancer cells. WERJFA arrested cell cycle, and caused apoptotic death in these cancer cells possibly via mitochondrial pathway involved with exceeding ROS level. PMID- 26684564 TI - Investigation of fibrous cap stresses on vulnerable plaques leading to heart attacks. AB - Rupture-prone plaques in the coronary arteries, called ''vulnerable plaques'', are recognized as the key factor in acute myocardial infarction. Vulnerable plaques have a thin fibrous cap over a large fatty core and are highly susceptible to rupture. In general, this type of plaque rupture is mainly associated with stress concentrated on the fibrous cap. Fibrous cap stresses are counted among the most important factors in the plaque rupture process and must be taken into consideration when assessing the plaque vulnerability leading to heart attacks. The objective of this paper was to investigate the effects of nitinol stent deployment on the morphological changes of vulnerable plaques and then to propose a new stent design concept for effectively reducing fibrous cap stresses and the associated rupture risk. The deployment of a self-expanding nitinol stent was modeled, and the resulting stress distribution on the fibrous cap was investigated. The fibrous cap stresses were more uniformly distributed and the maximum stress was reduced by 13% when the crown number of the stent was increased. This study demonstrates an excellent approach to stent design that could effectively reduce the risk of a vulnerable plaque rupturing and causing a heart attack. PMID- 26684565 TI - Simple electrocardiogram (ECG) signal analyzer for homecare system among the elderly. AB - This study presents a simple electrocardiogram (ECG) signal analyzer for homecare system among the elderly. It can transmit ECG signals of patient around his/her house through Bluetooth to computers in house. ECG signals are analyzed by the computer. If abnormal case of heartbeat is found, the emergency call is automatically dialed. Meanwhile, the determined heartbeat case of ECG signals will be forwarded to patient's MD through internet. Therefore, the patient can do whatever he/she wants around his/her house with our proposed simple cardiac arrhythmias signal analyzer. The proposed consists of five major processing stages: (i) preprocessing stage for enlarging ECG signals' amplitude and eliminating noises; (ii) ECG signal transmitter/receiver stage, ECG signals are transmitted through Bluetooth to the signal receiver in patient's house; (iii) QRS extraction stage for detecting QRS waveform using the Difference Operation Method (DOM) method; (iv) qualitative features stage for qualitative feature selection on ECG signals; and (v) classification stage for determining patient's heartbeat cases using the Principal Component Analysis (PCA) method. In the experiment, the total classification accuracy (TCA) was approximately 93.19% in average. PMID- 26684566 TI - The analysis of cardio-respiratory signals and cerebral autoregulation based on CO2 reactivity with healthy subjects and Parkinson's patients. AB - Current paper focus on Parkinson's patients with autonomic dysfunction and how their interactions between cerebral autoregulation and ventilatory control are affected. The experimental data of dynamic CA assessment from the ANS Laboratory of CCGH was accessed for further processing and analysis. The subjects were classified into the groups of healthy and with Parkinson's disease. Based on the accessed ventilation and CBF data, the percentage changes in ventilation and CBF responses to PETCO2 were examined. To minimize effects of changes in ABP on cerebral vasomotor reactivity (CVMR) estimation, cerebrovascular conductance index (CVCi) was calculated, and CBFV-PETCO2 and CVCi-PETCO2 relationships were quantified by nonlinear logistic regression. The interaction between ventilation responses and CBF autoregulation will be modeled and parameters will be validated. PMID- 26684567 TI - Systematic identification of multiple tumor types in microarray data based on hybrid differential evolution algorithm. AB - Correct classification and prediction of tumor cells are essential for microarrays to construct a diagnostic system. Differential evolution (DE) is a powerful optimization algorithm, which has been widely used in many areas. However, the standard DE and most of its variants search in the continuous space, which cannot solve the binary optimizations directly. In this paper, the hybrid framework based on the binary DE algorithm and silhouette filter, is proposed to improve searching ability to classify breast and leukemia cancers in microarray for biomarker discovery. The study is focused to use hybrid DE algorithm for gene selection and silhouette statistics as a discriminant function to classify multiple tumor types in microarray data. Distance metrics on silhouette statistics have also been discussed for high classification accuracy. Experimental results show that the hybrid method is effective to discriminate breast and leukemia cancer subtypes and find potential biomarkers for cancer diagnosis. PMID- 26684568 TI - Numerical evaluation and experimental validation of vascular access stenosis estimation. AB - Vascular access dysfunction commonly occurs in hemodialysis patients. Regularly monitoring and evaluating the vascular access condition is an important issue for these diseased patients. The objective of this study was to identify acoustic parameters and hemodynamics that related to changes in the stenosis of vascular access. In-vitro experimental circulation system offered pulsatile and physiological condition to simulate the arteriovenouse access in hemodialysis patient. We created the environments of various degrees of stenosis (DOS) inside the arteriovenouse access to simulate the stenotic conditions in patients. And we also used the computational fluid dynamics (CFD) to simulate the pressure distribution, primary axial velocity distribution, and secondary flow distribution in the same various DOS and boundary condition. There are two findings, one is recorded the bruit which caused by the fluctuation of fluid in different severe stenosis, the other is described the correlation between bruit and hemodynamic parameters. Experimental results show the time constants have linear regression with a positive correlation as the degree of stenosis (DOS) increases. Finally, in contrast to CFD computerized analysis and acoustic methods, the proposed parameter provides a feasibility index for evaluating the risk of AVG dysfunction in on-line/real time analysis. PMID- 26684569 TI - Multivariate adaptive regression splines based prediction of peak expiratory flow with spirometric data. AB - Spirometry evaluates the integrated function of lung capacity and chest wall mechanics measuring the total volume of air forcefully exhaled from a fully inflated lung. This non-invasive, informative technique for characterizing pulmonary function has an important role in clinical trials to narrow the differential diagnosis of subjects being assessed for pulmonary disorders. The test however requires patient co-operation and sometimes sub maximal effort affects the results potentially thereby leading to incomplete test and misdiagnosis. The aim of this work is to develop a prediction model based on Multivariate adaptive regression splines (MARS) technique to estimate the spirometric parameter Peak Expiratory Flow (PEF) volume. In the present study, flow-volume data from N = 220 subjects are considered. Model performances are evaluated statistically with coefficient of determination (R2) and Root Mean Squared Error (RMSE). The significant spirometric features captured in the model were FEV1, FEF50, FEF25 and the demographic parameter weight. Bland-Altman plots for the estimated PEF values showed a minimal bias. The MARS model successfully adopted the important features for prediction of PEF parameter with overall good fit and these findings can assist clinicians with enhanced spirometric investigations on respiratory disorders. PMID- 26684570 TI - A novel wireless health monitor by using a wearable rubber glove with three dimensional scanning elastic electrodes to measure acupuncture bio-potentials and impedances of a whole palm. AB - This paper proposes a novel wearable wireless-sensing technology on a glove to measure the bio-potentials and impedances of acupunctures on a whole palm in a non-invasive manner. Moreover, the device can transmit the information to a remote cloud server to learn at normal condition, and take measurement later for health condition analysis and monitoring. An example is given how to measure the acupuncture impedances and bio-potentials on a palm. One can see if certain acupuncture's impedance or bio-potential is not follow the Ohm's law or voltage divider rule along a meridian, then the health condition of the corresponding organ maybe with some problem. This discovery is not found in the previous literatures. PMID- 26684571 TI - The construction of the indicators of professional competence for exercise instructors of the elderly. AB - The purpose of this study was to construct the quality indicators of professional competence for exercise instructors of the elderly, and then to rank the importance among those indicators. This study used the Delphi technique to integrate the opinions of 11 experts to construct the indicators, and then adopts the analytic hierarchy process (AHP) to calculate the relative rank among each individual indicator. Results revealed that the experts identified 3 first-degree indicators (professional attitude, professional skills, and professional knowledge), 10 second-degree indicators (teaching attitude, exercise knowledge, professional growth, exercise safety, personal characteristics, exercise instructor, gerontology knowledge, communicative competence, curriculum design, and motor skill), and 72 third-degree indicators. In the indicator weighting system, professional attitude was the most important among all other first-degree indicators, and the teaching attitude was the most important among all other second-degree indicators. The results provided will help in planning the curriculums of training, professional growth and evaluation. The results also provide a reference for future research. PMID- 26684572 TI - Care pathway networks as a guideline for people with Dementia in Taiwan. AB - Dementia is a syndrome characterized by the progressive decline in cognitive function and memory that impairs a person's ability to function normally. Although dementia mainly affects older people, it is not a normal part of aging. The population of Taiwan is experiencing a multi-decade ageing trend and regrettably the absolute numbers of people with dementia is also rapidly rising. In 2008, the Taiwan Government initiated a ''Ten-Year Long-term Care Plan'' to categorize dementia's disability and severity, and it evaluates access to home care, respite care services, daycare or home nursing care. This review figure out the features of the features of ''Taiwan Dementia Policy: A Framework for Prevention and Care'' and discuss care pathway network as a guideline for people with dementia in Taiwan. The expectation is for many Taiwanese providers and patients in need simply don't know what services are available or how to access them. A properly designed dementia website could be one such effective tool to meet this need. There is an ongoing risk that future resources allocated will not reach the intended individuals unless this implementation problem is addressed urgently. PMID- 26684573 TI - Fluorescence reference plate for UV illumination using quantum dots. AB - Many image acquisition methods of nucleic acids still depend on UV illumination, especially after the electrophoresis when determining the size of the target DNA. Therefore the quality of the UV illuminator in the gel documentation system, and the comparison of the fluorescence detected are crucial. This paper presents a fluorescence standard reference plate using quantum dots compared to the conventional method where an agarose gel containing ethidium bromide is loaded with standard samples. The fluorescence standard reference plate consists of chambers filled with commercially available quantum dots such as phosphor dots. The chamber is made by thermally attaching nylon and polyester, the former on the inside and the latter on the outside, for increased stability. The images of the proposed reference plate were captured more than 2 months in regular intervals. The intensity analysis of the images shows that the proposed reference plate delivers stable fluorescence over a long term period. The proposed reference plate can be utilized to compare the performance of various UV illuminators, or to set a standard fluorescence point for certain analyses. PMID- 26684574 TI - Development a polymer-based electronic pulse diagnosis instrument for measuring and analyzing pulse wave velocity. AB - A novel pulse-diagnosis system was proposed in this study for measuring pulse wave velocities. In contrast with most conventional mechanical, rigid-type pulse diagnosis instruments such as pressure transducers and microactuators, a conductive elastic polymer was adopted as the sensor material. The soft and formability properties of such material enabled fabricating a flexible pulse diagnosis instrument. In addition, the flexible design was integrated with a contemporary, wrist-type pulse-wave acquisition system to ensure stable measurements. Closely related to the incidence of cardiovascular diseases, pulse wave velocity was analyzed in applications to verify the feasibility of this system. Regarding signal processing, the cun, guan, and chi pulse signals obtained through the data acquisition device were sent to the LabVIEW platform for reconstructing the pulse waveforms. Finally, the results of 20 measured samples were compared and analyzed to evaluate the level of system performance. PMID- 26684575 TI - Hepatobiliary and Pancreatic: Plate-like atelectasis mimics pneumoperitoneum in patient with acute gangrenous cholecystitis. PMID- 26684577 TI - Use of Process Improvement Tools in Radiology. AB - Process improvement techniques are common in manufacturing and industry. Over the past few decades these principles have been slowly introduced in select health care settings. This article reviews the Plan, Do, Study, and Act cycle, Six Sigma, the System of Profound Knowledge, Lean, and the theory of constraints. Specific process improvement tools in health care and radiology are presented in the order the radiologist is likely to encounter them in an improvement project. PMID- 26684576 TI - One Health in Practice: A Pilot Project for Integrated Care of Zoonotic Infections in Immunocompromised Children and Their Pets in Chile. AB - Although pets provide physiological and psychological benefits to their owners, they are a potential source of zoonotic infections, especially for vulnerable individuals such as immunocompromised patients. During 1 year, we therefore performed a pilot project, which included 32 immunocompromised Chilean children and their family pets (35 dogs and 9 cats) with the aim of detecting, treating and preventing zoonotic infections. Children were examined by Infectious Diseases paediatricians and demographical and clinical information related to zoonotic infections were recorded. Pets were examined and sampled by veterinarians, who also administered missing routine vaccines and anti-parasitics. During family visits, all members were informed and educated about zoonoses and a satisfaction survey was performed. Visits also included vector control and indoor residual spraying with pyrethroids. Children were re-examined and re-tested according to the findings of their pets, and all detected zoonotic infections were treated both in children and pets. Physical examination revealed abnormalities in 18 dogs (51.4%) and three cats (33.3%). Twenty-eight (63.6%) of the pets were diagnosed with a zoonotic pathogen, and seven (15.9%) with a facultative pathogen. Most zoonotic agents were isolated from the pet's external ear and intestine. Bacteria with the highest pathogenic potential were Campylobacter jejuni and Brucella canis. In two children and their respective pets, the same zoonotic diseases were diagnosed (toxocariasis and giardiasis). Arthropods serving as potential vectors of zoonotic infections were found in 49% of dogs and 44% of cats. The pilot project was positively evaluated by the participating families. Our pilot project confirmed that pets are reservoir for various zoonotic agents in Chile and that the implementation of an integrated multidisciplinary programme was a valuable tool to prevent, diagnose and treat such zoonotic infections in vulnerable patients such as immunocompromised children. PMID- 26684578 TI - Determination of Normal Distribution of Distended Colon Volumes to Guide Performance of Colonic Imaging With Fluid Distention. AB - The purpose was to determine the normal distribution of distended colon volumes as a guide for rectal contrast material administration protocols. All computed tomography colonography studies performed at Emory University Hospital, Atlanta, Georgia, between January 2009 and January 2015, were reviewed retrospectively. In total, 85 subjects were included in the analysis (64% [54 of 85] female and 36% [31 of 85] male). Mean patient age was 65 years (range: 42-86y). Distended colon volumes were determined from colon length and transaxial diameter measurements made using a 3-dimensional workstation. Age, sex, race, height, weight, and body mass index were recorded. The normal distributions of distended colon volumes and lengths were determined. Correlations between colonic volume and colonic length, and demographic variables were assessed. Mean colon volume was 2.1L (range: 0.7 4.4L). Nearly, 17% of patients had a distended colonic volume of >3L. Mean colon length was 197cm (range: 118-285cm). A weak negative correlation was found between age and colonic volume (r = -0.221; P = 0.04). A weak positive correlation was found between body mass index and colonic length (r = 0.368; P = 0.007). Otherwise, no significant correlations were found for distended colonic volume or length and demographic variables. In conclusion, an average of approximately 2L of contrast material may be necessary to achieve full colonic opacification. This volume is larger than previously reported volumes (0.8-1.5L) for rectal contrast material administration protocols. PMID- 26684579 TI - Synthesis and characterization of (3-Aminopropyl)trimethoxy-silane (APTMS) functionalized Gd2O3:Eu(3+) red phosphor with enhanced quantum yield. AB - We report the surface modification of nanocrystalline Gd2O3:Eu(3+) phosphor by (3 Aminopropyl)trimethoxysilane (APTMS). The nanoparticles were first coated with silica using the Stober process, and then annealed at 650 degrees C for 2 h. Afterwards, APTMS was functionalized onto the silica layer to obtain Gd2O3:Eu(3+) nanoparticles bearing amine groups on the surface. The effect of silica coating, and the subsequent annealing process on the crystallization of the nanophosphor were analyzed by x-ray diffraction (XRD). High-resolution transmission electron microscopy (HR-TEM) confirmed the presence of a silica layer of ~45 nm thickness. X-ray photoelectron (XPS) and Fourier transform infrared (FTIR) spectroscopy confirmed the presence of silica and the amine groups. Photoluminescence (PL) analysis demonstrated an increased emission after functionalization of nanoparticles. Absolute quantum yield (QY) measurements revealed an 18% enhancement in QY in functionalized nanoparticles compared with unmodified nanoparticles, which is of great importance for their biomedical applications. PMID- 26684581 TI - Novel No-Wash Luminogenic Probes for the Detection of Transporter Uptake Activity. AB - Luminogenic probes were designed and synthesized for the detection of uptake transporter activity in a lytic cell-based assay. These probes rely on a self cleavable trimethyl lock quinone-cyanobenzothiazole (TMQ-CNBT) or trimethyl lock quinone-luciferin (TMQ-Luc) linked to the anion transporter substrate fluorescein. Upon cellular transport, the TMQ is reduced by viable cells, resulting in the facile intramolecular lactonization and rapid release of the bioluminescent reporter molecule. The uptake transporter activity can then be detected without removing and washing off the extracellular substrates. Six probes were tested with OATP1B1*1a and OATP1B3 overexpressing HEK293 cells, and all compounds showed up to 10.2-fold enhancement in uptake when compared to control cells. Uptake of TMQ-luciferin compounds 2, 4, and 6 increased linearly over time up to 30 min at a concentration ranging from 40 nM to 20 MUM. The apparent Km values obtained at different time intervals up to 30 min were nearly identical for a given compound, which validates the 30 min window as appropriate for uptake transporter assays. The average apparent Km values ranged from 0.3 to 0.8 MUM and 0.2 to 1.3 MUM for OATP1B1*1a and OATP1B3, respectively, indicating good affinities to these anion transporters. Furthermore, uptake of compound 2 was inhibited by two inhibitors of OATP1B1*1a and OATP1B3: rifampicin and ritonavir. The preliminary results obtained from compound 2 exhibited a time dependent, saturatable, and inhibitable nature of uptake, indicating the feasibility of using the probe for the detection of a transporter-mediated process. This add-and-read homogeneous assay may provide a convenient, rapid, and facile way to detect changes in transporter activity in a high-throughput format, and this assay design strategy could create a new platform for a general cell uptake assay for biomaterials in the future. PMID- 26684582 TI - Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl) pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity. AB - Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5 perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1 methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4 triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)2].1.5 DMSO (2a), [PtCl2(pfpop)2].1.5 DMSO (3a), [PtCl2(pfhtp)2].1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(pfptp)2].1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) staining. PMID- 26684580 TI - Gene fusions in soft tissue tumors: Recurrent and overlapping pathogenetic themes. AB - Gene fusions have been described in approximately one-third of soft tissue tumors (STT); of the 142 different fusions that have been reported, more than half are recurrent in the same histologic subtype. These gene fusions constitute pivotal driver mutations, and detailed studies of their cellular effects have provided important knowledge about pathogenetic mechanisms in STT. Furthermore, most fusions are strongly associated with a particular histotype, serving as ideal molecular diagnostic markers. In recent years, it has also become apparent that some chimeric proteins, directly or indirectly, constitute excellent treatment targets, making the detection of gene fusions in STT ever more important. Indeed, pharmacological treatment of STT displaying fusions that activate protein kinases, such as ALK and ROS1, or growth factors, such as PDGFB, is already in clinical use. However, the vast majority (52/78) of recurrent gene fusions create structurally altered and/or deregulated transcription factors, and a small but growing subset develops through rearranged chromatin regulators. The present review provides an overview of the spectrum of currently recognized gene fusions in STT, and, on the basis of the protein class involved, the mechanisms by which they exert their oncogenic effect are discussed. PMID- 26684583 TI - Effect of concomitant oxidation and deprotonation of hydrated Mn centres in rationalising the FTIR difference silence of D1-Asp170 in Photosystem II. AB - The observation of negligible FTIR differences in carboxylate vibrational modes for the D1-Asp170 residue of Photosystem II (PSII) on successive one-electron oxidations of the Mn4CaO5 oxygen-evolving complex (OEC) is counterintuitive in light of the apparent ligation of D1-Asp170 to an oxidisable Mn ion in the X-ray crystallographic structures of PSII. Here, we show computational support for the hypothesis that suppression of the FTIR difference spectrum in the 1100cm(-1) to 1700cm(-1) region of D1-Asp170 occurs by concomitant Mn oxidation and deprotonation of water ligands bound to the ligated metal centre. Density functional theory calculations on the model species [Mn(II)Ca(COOH)(OH)2(H2O)2](+) over two successive oxidations of the Mn ion are performed, where those oxidations are accompanied by deprotonation of water and MU-hydroxo ligands coordinated to the Mn ion. In contrast, dramatically increased FTIR difference activity is observed where these oxidations are unaccompanied by proton loss. PMID- 26684584 TI - Letter to the editor: In response to: lifestyle medicine in Expert Review of Cardiovascular Therapy. PMID- 26684585 TI - Characterization of the 5'-flanking region of the human TP53 gene and its response to the natural compound, Resveratrol. AB - Tumour suppressor p53, which is encoded by theTP53gene, is widely known to play an important role in response to DNA damage and various stresses. It has recently been reported that p53 regulates glucose metabolism and that an increase in p53 protein level is induced after serum deprivation or treatments with a natural compound,trans-Resveratrol (Rsv). In this study, we constructed a Luciferase expression vector, pGL4-TP53-551, containing 551 bp of the 5'-upstream region of the humanTP53gene, which was then transfected into HeLa S3 cells. A Luciferase assay showed that Rsv treatment increased the promoter activity of theTP53gene in comparison to that ofPIF1 Detailed deletion and mutation analyses revealed that Nkx-2.5 and E2F-binding elements are required in addition to duplicated GGAA (TTCC), for the regulation ofTP53promoter activity. In this study, it is suggested that the transient induction ofTP53gene expression by Rsv treatment might be partly involved in its anti-aging effect through maintenance of chromosomal DNAs. PMID- 26684587 TI - Optical Actuation of Inorganic/Organic Interfaces: Comparing Peptide-Azobenzene Ligand Reconfiguration on Gold and Silver Nanoparticles. AB - Photoresponsive molecules that incorporate peptides capable of material-specific recognition provide a basis for biomolecule-mediated control of the nucleation, growth, organization, and activation of hybrid inorganic/organic nanostructures. These hybrid molecules interact with the inorganic surface through multiple noncovalent interactions which allow reconfiguration in response to optical stimuli. Here, we quantify the binding of azobenzene-peptide conjugates that exhibit optically triggered cis-trans isomerization on Ag surfaces and compare to their behavior on Au. These results demonstrate differences in binding and switching behavior between the Au and Ag surfaces. These molecules can also produce and stabilize Au and Ag nanoparticles in aqueous media where the biointerface can be reproducibly and reversibly switched by optically triggered azobenzene isomerization. Comparisons of switching rates and reversibility on the nanoparticles reveal differences that depend upon whether the azobenzene is attached at the peptide N- or C-terminus, its isomerization state, and the nanoparticle composition. Our integrated experimental and computational investigation shows that the number of ligand anchor sites strongly influences the nanoparticle size. As predicted by our molecular simulations, weaker contact between the hybrid biomolecules and the Ag surface, with fewer anchor residues compared with Au, gives rise to differences in switching kinetics on Ag versus Au. Our findings provide a pathway toward achieving new remotely actuatable nanomaterials for multiple applications from a single system, which remains difficult to achieve using conventional approaches. PMID- 26684588 TI - Cardiovascular and cerebrovascular outcomes of long-term angiotensin receptor blockade: meta-analyses of trials in essential hypertension. AB - Angiotensin receptor blockers (ARBs) are widely used in managing essential hypertension, with considerable evidence available on their short-term efficacy in lowering blood pressure (BP). However, there currently exists limited "pooled" data examining the long-term efficacy of ARB treatment in controlling BP or mitigating cardiovascular and cerebrovascular events. The purpose of this study was to conduct a systematic review and meta-analysis assessing the long-term effects of ARBs as a class on BP control, myocardial infarction, hospitalization for heart failure, cerebrovascular events (ie, stroke), cardiovascular mortality, and all-cause mortality. MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched from inception to March 2015. Two evaluators independently reviewed studies for eligibility. Randomized controlled hypertension trials were included if they reported on ARB efficacy in either BP control (relative to placebo for periods >= 6 months) or cardiovascular/cerebrovascular outcomes (relative to non-ARB antihypertensive therapies for periods >= 24 months). Studies were pooled with a random-effects model using weighted mean differences (WMDs) and relative risks for continuous and dichotomous outcomes, respectively. A total of 11 articles were included in the narrative synthesis, representing seven unique trials (16,864 participants). Six ARB agents were studied: candesartan, eprosartan, irbesartan, olmesartan, losartan (each represented by one trial arm), and telmisartan (represented by two arms). ARB therapy significantly reduced mean systolic BP (WMD: -4.86; 95% CI: 6.19, -3.53 mm Hg) and diastolic BP (WMD: -2.75; 95% CI: -3.65, -1.86 mm Hg] compared to placebo. The risk of stroke was reduced by 21% in the ARB group compared with alternative antihypertensives (risk ratio: 0.79; 95% CI: 0.66, 0.96). ARBs did not, however, produce statistically significant reductions in the risk of myocardial infarction, heart failure hospitalization, or mortality. Our findings suggest that ARBs, as a class, are more effective than placebo therapy in long-term BP lowering in patients with essential hypertension. Long-term ARB treatment may also confer enhanced protection against stroke but not other cardiovascular outcomes relative to placebo. PMID- 26684589 TI - Is arterial stiffness predicted by continuous metabolic syndrome score in obese children? AB - The aim of the article was to evaluate arterial stiffness, an early marker of increased cardiovascular risk, in relation to obesity. The continuous metabolic syndrome (cMetS) score was calculated as sum of Z score of mean arterial pressure, body mass index, serum glucose, triglyceride, and high-density lipoprotein cholesterol in 144 obese patients and 66 nonobese controls. Ambulatory arterial stiffness index (AASI) was calculated as 1 minus regression slope of diastolic on systolic blood pressure from ambulatory blood pressure measurements. The mean AASI increased progressively with severity of obesity. The receiver operator curve analysis of body mass index and AASI showed area under the curve of 0.64 +/- 0.06; cMetS area under the curve was 0.72 +/- 0.05 suggesting a better predictive power of the cMetS for an increased AASI (>0.3). Patients with obesity have significantly higher arterial stiffness. A composite score such as cMetS seems to be better predictor of an increased stiffness than individual risk factors. PMID- 26684590 TI - Knowns and unknowns of influenza B viruses. AB - Influenza B viruses (IBVs) circulate annually along with influenza A (IAV) strains during seasonal epidemics. IBV can dominate influenza seasons and cause severe disease, particularly in children and adolescents. Research has revealed interesting aspects of IBV and highlighted the importance of these viruses in clinical settings. Yet, many important questions remain unanswered. In this review, the clinical relevance of IBV is emphasized, unique features in epidemiology, host range and virology are highlighted and gaps in knowledge pinpointed. Multiple aspects of IBV epidemiology, evolution, virology and immunology are discussed. Future research into IBV is needed to understand how we can prevent severe disease in high-risk groups, especially children and elderly. PMID- 26684586 TI - Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. AB - Basigin, also called CD147 or EMMPRIN, is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Basigin has isoforms; the common form (basigin or basigin-2) has two immunoglobulin domains, and the extended form (basigin-1) has three. Basigin is the receptor for cyclophilins, S100A9 and platelet glycoprotein VI, whereas basigin-1 serves as the receptor for the rod derived cone viability factor. Basigin tightly associates with monocarboxylate transporters and is essential for their cell surface translocation and activities. In the same membrane plane, basigin also associates with other proteins including GLUT1, CD44 and CD98. The carbohydrate portion of basigin is recognized by lectins, such as galectin-3 and E-selectin. These molecular recognitions form the basis for the role of basigin in the transport of nutrients, migration of inflammatory leukocytes and induction of matrix metalloproteinases. Basigin is important in vision, spermatogenesis and other physiological phenomena, and plays significant roles in the pathogenesis of numerous diseases, including cancer. Basigin is also the receptor for an invasive protein RH5, which is present in malaria parasites. PMID- 26684591 TI - Introduction to Special Issue: Ready to Link Oral Health to Systems Medicine and Next Generation Biomarkers? PMID- 26684592 TI - Comparative study of comprehensive gas chromatography-nitrogen chemiluminescence detection and gas chromatography-ion trap-tandem mass spectrometry for determining nicotine and carcinogen organic nitrogen compounds in thirdhand tobacco smoke. AB - Thirdhand tobacco smoke (THS) constitutes a poorly understood pathway of exposure of non-smokers, especially toddlers, to tobacco-related carcinogens. However, to date most of the carcinogens present in tobacco smoke have not been detected in THS and, therefore, the significance of THS health risk is still unknown. In this study, we have compared the performance of two analytical methods - one based on gas chromatography coupled to ion trap mass spectrometry detection (GC-IT-MS) and the other on comprehensive two-dimensional gas chromatography coupled to a nitrogen chemiluminescence detector (GC*GC-NCD) - for simultaneously determining, in settled house dust, the presence of 16 organic nitrogen carcinogens already detected in tobacco smoke. The target compounds included four aromatic amines, two nitrocompounds, eight N-nitrosamines and two tobacco-specific nitrosamines, as well as nicotine as a tobacco marker. Dust samples were extracted using in cell clean up pressurized liquid extraction with silica as clean up sorbent and ethyl acetate as the organic solvent, with average recovery of 89%. Although GC IT-MS, using chemical ionization with methanol and tandem MS, performed well, the optimized GC*GC-NCD gave lower limits of detection (from 4 to 22ngg(-1)) and better repeatability and reproducibility a low concentration levels (%RSD<8%) and, therefore, was applicable for determining these different groups of carcinogens without the need for derivatization prior to the GC analysis. The performance of the optimized PLE/GC*GC-NCD method was tested by quantifying the target compounds in house dust samples from smokers' and non-smokers' homes. The median carcinogen compounds detected was 3.8MUgg(-1) and 1.1MUgg(-1) in smokers' and non-smokers' house dust, respectively. In this study, we have detected highly carcinogenic aromatic amines and nitro compounds for the first time in settled house dust complementing the state of knowledge of THS composition and providing fresh evidence about THS health risks. PMID- 26684594 TI - Contemporary Management of Acute Type B Dissection. AB - OBJECTIVE: Growing confidence in thoracic endovascular aortic repair (TEVAR) for the management of acute type B aortic dissection has resulted in controversies regarding optimum patient selection and the timing of intervention. In this review a clinical vignette to present a practical perspective on the contemporary management of acute type B dissection (ABAD) in a specialist vascular centre with particular focus on areas of debate is used. METHODS: This is a narrative clinical review. RESULTS: Aggressive anti-impulse therapy is the cornerstone of management of all patients with ABAD. However, 20-30% of patients develop complicated ABAD defined by the presence of malperfusion syndromes, acute aortic dilatation, dissection extension, or persistent pain and hypotension. These complicated patients typically require intervention, and non-randomised series suggest TEVAR to be an effective alternative to open repair with a lower morbidity. There is considerable interest and controversy surrounding the use of TEVAR in uncomplicated ABAD patients for whom the intervention-free survival at 6 years is less than 50% for patients managed with anti-impulse therapy. Data regarding this question are sparse, but two randomised trials (ADSORB and INSTEAD) both demonstrated a higher rate of favourable aortic remodelling in patients managed with TEVAR than medical therapy alone. However, it is unclear whether this positive remodelling translates into a reduction in long-term mortality sufficient to balance the early perioperative hazards of endografting. CONCLUSION: Despite increasing adeptness at endovascular stenting, the long-term outcomes of patients with ABAD leave significant room for improvement. In particular, the optimum management of patients with uncomplicated disease is unclear and guidance from trials powered for long-term mortality is awaited. Until then, the principals of management of ABAD remain aggressive medical therapy for all patients, with TEVAR primarily reserved for those who develop complications. PMID- 26684593 TI - Graphene oxide-based dispersive solid-phase extraction combined with in situ derivatization and gas chromatography-mass spectrometry for the determination of acidic pharmaceuticals in water. AB - A fast and low-cost sample preparation method of graphene based dispersive solid phase extraction combined with gas chromatography-mass spectrometric (GC-MS) analysis, was developed. The procedure involves an initial extraction with water immiscible organic solvent, followed by a rapid clean-up using amine functionalized reduced graphene oxide as sorbent. Simple and fast one-step in situ derivatization using trimethylphenylammonium hydroxide was subsequently applied on acidic pharmaceuticals serving as model analytes, ibuprofen, gemfibrozil, naproxen, ketoprofen and diclofenac, before GC-MS analysis. Extraction parameters affecting the derivatization and extraction efficiency such as volume of derivatization agent, effect of desorption solvent, effect of pH and effect of ionic strength were investigated. Under the optimum conditions, the method demonstrated good limits of detection ranging from 1 to 16ngL(-1), linearity (from 0.01 to 50 and 0.05 to 50MUgL(-1), depending on the analytes) and satisfactory repeatability of extractions (relative standard deviations, below 13%, n=3). PMID- 26684595 TI - Re: 'How Should I Treat a Patient with a Tandem Carotid Artery Atherosclerotic Stenosis Involving the Internal Carotid Artery and the Innominate/Proximal Common Carotid Artery?'. PMID- 26684596 TI - Commentary on "Temporary Abdominal Closure after Abdominal Aortic Aneurysm Repair - A Systematic Review of Contemporary Observational Studies". PMID- 26684597 TI - Evidence for Endovascular Simulation Training: A Systematic Review. AB - BACKGROUND: Simulation training in endovascular surgery provides opportunities for trainees to practice and learn from non-patient based experience. Several types of endovascular simulators are available commercially. Previous studies on endovascular simulation training can be categorized into trials in which only a simulator was used when measuring performance metrics or "trials within simulation"; patient specific procedure rehearsals; and randomized, controlled trials (RCTs) or translational studies. OBJECTIVES: To examine whether endovascular simulation training can improve surgeon techniques and patient outcomes in real clinical settings. METHODS: A literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement. All searches were done via PubMed and Embase. Review articles, and papers that were not related to endovascular surgery and not within the scope of interest were excluded. References of review articles were further screened according to the exclusion criteria. RESULTS: In total, 909 records were identified and 290 duplicates were removed. Thirty-one were included in the qualitative analysis. Twenty-three were trials within simulation and most of them found statistically significant improvements in procedure time, fluoroscopy time, and contrast volume. Five were patient specific procedure rehearsals and showed that simulation significantly affected the fluoroscopy angle and improved performance metrics. Three were RCTs and revealed mainly positive results on a Global Rating Scale and procedure specific rating scale. CONCLUSIONS: Contemporary evidence shows that performance metrics within endovascular simulations improve with simulation training. Successful translation to in vivo situations is observed in patient specific procedure rehearsals and RCTs on real procedures. However, there is no level I evidence to show that predictive validity of simulation can definitively improve patient outcomes. Current literature supports the idea that there is a beneficial role of simulation in endovascular training. Future studies are needed to confirm the efficacy of simulation in endovascular surgical training and to see if simulation is superior to traditional training in the operating theatre. PMID- 26684598 TI - Two Types of Anion-Induced Reconstruction of Schiff-Base Macrocyclic Zinc Complexes: Ring-Contraction and Self-Assembly of a Molecular Box. AB - Two 46-membered [2 + 2] Schiff-base macrocyclic dinuclear Zn(II) complexes (1a and 1b) were investigated deeply by the postmodification strategy, and two types of supramolecular processes (ring-contraction and self-assembly) have been achieved after the addition of specific anions as stimulus for the equilibrium of Schiff-base macrocyclic complexes. Namely, in the presence of linear three-atom SCN(-), 1a was degraded into two 23-membered [1 + 1] Schiff-base macrocyclic complexes simultaneously (mononuclear Zn(II) complex 2 and dinuclear Zn(II) complex 3). In contrast, 1b was only transformed into the macrocyclic mononuclear complex 5. More interestingly, in the case of pseudolinear five-atom N(CN)2(-), supramolecular self-assembly took place instead of the above-mentioned ring contraction. Finally, 1a was assembled into a unique molecular box 4 with two 46 membered [2 + 2] Schiff-base macrocyclic heteronuclear Zn4Na4 substrates and double MU2-N(CN)2(-) bridges, while no similar assembly process was observed for 1b. The geometry of anions and pH values slightly adjusted by the pendant arms on the macrocyclic skeletons are believed to be the critical factors for the different supramolecular processes originating from the dynamic covalent chemistry of Schiff-base imine bonds. PMID- 26684599 TI - Feasibility of laparoscopic and endoscopic cooperative surgery for gastric submucosal tumors (with video). AB - BACKGROUND AND AIMS: Laparoscopic gastric resection is widely used for gastric submucosal tumors (SMTs). However, determining an appropriate resection line using only the laparoscopic approach is difficult. We developed a laparoscopic and endoscopic cooperative surgery (LECS) technique by combining laparoscopic gastric resection with endoscopic submucosal dissection, and we have used this procedure to resect gastric SMTs. In this study, the procedure is presented and its safety and feasibility for resecting gastric SMTs are evaluated. METHODS: This retrospective study included 100 patients who underwent LECS for SMTs at the Department of Gastroenterological Surgery, Cancer Institute, between June 2006 and November 2014. The demographics, tumor histopathologic characteristics, and operative and follow-up data were reviewed. RESULTS: Complete resection with negative surgical margins was achieved in all patients, and LECS was performed regardless of tumor location. The mean operation time was 174.3 minutes, with an estimated blood loss of 16.3 mL. In addition, the mean time until the initiation of oral intake was 1.4 days, and the mean postoperative hospital stay was 8.4 days. Moreover, no local or distant tumor recurrence was observed. The only severe adverse event was leakage, which was observed in 1 patient. CONCLUSIONS: LECS was performed with a reasonable operation time, low blood loss, and minimal adverse events. Therefore LECS is safe and feasible for resecting gastric SMTs. PMID- 26684600 TI - EUS-guided portal pressure measurement using a digital pressure wire with real time remote display: a novel, minimally invasive technique for direct measurement in an animal model. AB - BACKGROUND AND AIMS: Hepatic venous pressure gradient (HVPG) currently serves as a surrogate for portal pressure measurement but has many limitations. We developed a novel technique for rapid and direct portal pressure measurements using a digital pressure wire delivered through an EUS-guided 22-gauge FNA needle. Our aims were to evaluate (1) the short-term safety and technical feasibility, (2) procedural duration and subjective workload assessment, and (3) accuracy compared with a transjugular criterion standard approach. METHODS: The subjects were Yorkshire pigs, weighing 40 to 55 kg. The portal vein was identified by using a linear array echoendoscope and accessed with a commercially available 22-gauge FNA needle preloaded with a digital pressure wire. Access was confirmed by portal venography. Mean digital pressure measurements were recorded over 30 to 60 seconds, and the National Aeronautics and Space Administration Task Load Index was scored. The control measurements were conventional transjugular catheterization with a balloon occlusion catheter to obtain free and wedged hepatic pressures, with subsequent HVPG calculation. RESULTS: The total time required for EUS identification and needle access of the portal vein, venography, and digital pressure measurement was less than 5 minutes in 5 of 5 pigs. The National Aeronautics and Space Administration Task Load Index scores revealed a low subjective workload. Baseline portal pressure measurements via EUS ranged from 5 mm Hg to 10 mm Hg (mean, 6.4 mm Hg). HVPG measurements were consistently +/-1 mm Hg of portal pressure. CONCLUSIONS: This study is the first report of direct EUS-guided portal pressure measurements by using a digital pressure wire. This method is routinely performed in minutes and provides real-time pressure tracings via wireless transmission. This novel approach for direct portal pressure measurement has the potential to replace traditional indirect HVPG measurements. PMID- 26684601 TI - Ex vivo comparison of the lumen-apposing properties of EUS-specific stents (with video). AB - BACKGROUND AND AIMS: Several EUS-specific stents have become available. It has been claimed that some of these stents have lumen-apposing properties, but objective data measuring such properties are not available. The aim of this study is to measure the lumen-apposing force (LAF) of these stents. METHODS: The LAF of 3 EUS-specific metallic stents (stents A, N, and S) were compared in an ex vivo setting. Four types of anastomoses were performed with the stents including cholecysto-duodenal, cholecysto-gastric, gastro-gastric, and gastro-jejunal and compared with a hand-sewn (HS) equivalent of the anastomosis. The outcome parameter was the LAF created by each type of stent. RESULTS: Sixty-four anastomoses were created. The overall mean (standard deviation) LAFs were significantly higher for stents A and S (P < .001). This difference persisted regardless of the type of anastomosis: gastro-gastric (P = .002), gastro-jejunal (P = .005), cholecysto-gastric (P = .002), and cholecysto-jejunal (P = .003). The differences in LAF created by each type of stent across different types of anastomoses were also compared. A trend to significance was observed in the anastomoses created by stent N (P = .064) and stent A (P =.052); a significant difference in LAF was observed among different anastomoses created by stent S (P = .015). The LAF created by HS anastomosis was significantly higher than that for all stents across all anastomoses. CONCLUSIONS: Stents A and S had a higher LAF. The use of these stents should be considered when performing EUS-guided transmural luminal anastomoses in non-adherent organs. Further studies are required to confirm the clinical efficacies of these EUS-specific stents. PMID- 26684602 TI - Endoscopic choledochoduodenostomy and gastrojejunostomy in the treatment of biliary and duodenal obstruction. PMID- 26684603 TI - Modified endoscopic submucosal dissection techniques before endoscopic revision of a gastric bypass. PMID- 26684605 TI - Novel approach to recanalizing an occluded cystic duct after cholecystoduodenostomy by lumen-apposing metal mesh stent for malignant obstructive jaundice. PMID- 26684604 TI - Fluorescence in situ hybridization compared with conventional cytology for the diagnosis of malignant biliary tract strictures in Asian patients. AB - BACKGROUND AND AIMS: Fluorescence in situ hybridization (FISH) has improved the diagnostic performance of cytology for the evaluation of malignant biliary strictures in the United States and Europe. The utility of FISH for the diagnosis of biliary strictures in Asia is currently unknown. We aimed to compare the sensitivity of FISH and conventional cytology for the diagnosis of malignant biliary strictures in Thai patients. METHODS: A prospective study was performed at 2 university hospitals between 2010 and 2013. Patients being evaluated for malignant-appearing biliary strictures were included (N = 99). Bile duct brushings were collected and assessed by cytology and FISH. Sensitivities with 95% confidence intervals of cytology and FISH were the main outcome measures. RESULTS: The overall sensitivities of cytology and FISH were 38% and 55%, respectively (P = .001). For those with a diagnosis of cancer based on clinical evidence without biopsy confirmation (n = 44), the sensitivities of cytology and FISH were 43% and 57%, respectively (P = .06). For the 49 patients for whom a cancer diagnosis was confirmed by pathology, FISH had a significantly higher sensitivity than cytology, with a sensitivity of 53% versus 33%, respectively (P = .008). CONCLUSIONS: FISH improves the diagnostic performance of cytology and can be used as a complementary tool to bile duct brushing and biopsy for the evaluation of malignancy in biliary strictures in Asian populations. PMID- 26684606 TI - Endoscopic removal of ingested nitrile gloves. PMID- 26684608 TI - Isavuconazole: a role for the newest broad-spectrum triazole. PMID- 26684607 TI - Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised controlled, non-inferiority trial. AB - BACKGROUND: Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease. METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of -1.0% (95% CI -7.8 to 5.7). Because the upper bound of the 95% CI (5.7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0.122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0.016), eye disorders (39 [15%] vs 69 [27%]; p=0.002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0.037). Drug related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0.001). INTERPRETATION: Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International. PMID- 26684610 TI - Happiness and unhappiness have no direct effect on mortality. PMID- 26684611 TI - Alcohol advertising influences underage brand-specific drinking: evidence of a linear dose-response relationship. PMID- 26684609 TI - Does happiness itself directly affect mortality? The prospective UK Million Women Study. AB - BACKGROUND: Poor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality. METHODS: The Million Women Study is a prospective study of UK women recruited between 1996 and 2001 and followed electronically for cause-specific mortality. 3 years after recruitment, the baseline questionnaire for the present report asked women to self-rate their health, happiness, stress, feelings of control, and whether they felt relaxed. The main analyses were of mortality before Jan 1, 2012, from all causes, from ischaemic heart disease, and from cancer in women who did not have heart disease, stroke, chronic obstructive lung disease, or cancer at the time they answered this baseline questionnaire. We used Cox regression, adjusted for baseline self-rated health and lifestyle factors, to calculate mortality rate ratios (RRs) comparing mortality in women who reported being unhappy (ie, happy sometimes, rarely, or never) with those who reported being happy most of the time. FINDINGS: Of 719,671 women in the main analyses (median age 59 years [IQR 55-63]), 39% (282,619) reported being happy most of the time, 44% (315,874) usually happy, and 17% (121,178) unhappy. During 10 years (SD 2) follow-up, 4% (31,531) of participants died. Self-rated poor health at baseline was strongly associated with unhappiness. But after adjustment for self-rated health, treatment for hypertension, diabetes, asthma, arthritis, depression, or anxiety, and several sociodemographic and lifestyle factors (including smoking, deprivation, and body-mass index), unhappiness was not associated with mortality from all causes (adjusted RR for unhappy vs happy most of the time 0.98, 95% CI 0.94-1.01), from ischaemic heart disease (0.97, 0.87-1.10), or from cancer (0.98, 0.93-1.02). Findings were similarly null for related measures such as stress or lack of control. INTERPRETATION: In middle-aged women, poor health can cause unhappiness. After allowing for this association and adjusting for potential confounders, happiness and related measures of wellbeing do not appear to have any direct effect on mortality. FUNDING: UK Medical Research Council, Cancer Research UK. PMID- 26684612 TI - Detection of Pathogenic Biofilms with Bacterial Amyloid Targeting Fluorescent Probe, CDy11. AB - Bacterial biofilms are responsible for a wide range of persistent infections. In the clinic, diagnosis of biofilm-associated infections relies heavily on culturing methods, which fail to detect nonculturable bacteria. Identification of novel fluorescent probes for biofilm imaging will greatly facilitate diagnosis of pathogenic bacterial infection. Herein, we report a novel fluorescent probe, CDy11 (compound of designation yellow 11), which targets amyloid in the Pseudomonas aeruginosa biofilm matrix through a diversity oriented fluorescent library approach (DOFLA). CDy11 was further demonstrated for in vivo imaging of P. aeruginosa in implant and corneal infection mice models. PMID- 26684613 TI - Enhancement of Cognitive Functions by Aronia melanocarpa Elliot Through an Intermittent Ultrasonication Extraction Process. AB - To increase the cognitive enhancement provided by Aronia melanocarpa Elliot (Aronia), Aronia was extracted using 70% ethanol solvent and six cycles of intermittent ultrasonication at 120 KHz for 50 min, followed by a rest for 10 min (UE), and was also extracted using 70% ethanol for 24 h at 80 degrees C (EE) as a control process. In both in vivo water maze and passive avoidance tests, the UE showed better performance enhancement than the EE: in the water maze, mice treated with EE and UE showed escape latencies of 62.6 s and 54.3 s, respectively; for passive avoidance, they showed retention times of 45.9 s and 38.9 s, respectively. UE downregulated the expression level of acetylcholinesterase genes to 1.46 times compared with 1.72 for EE. However, there were no significant histological differences in the hippocampus between the mice fed with EE and those fed UE. Additionally, the UE was confirmed to have a greater antioxidant effect, 0.728 versus 0.561 for EE. Comparison of the high performance liquid chromatography chromatograms of the extracts demonstrates that the intermittent ultrasonication process may improve the cognitive activities of Aronia by eluting higher amounts of cyanidin-3-galactoside (C3G). This work is the first to report that the crude extract from the intermittent ultrasonication process provided better cognitive enhancement than a single major bioactive substance, C3G itself, possibly through the synergistic effects of other anthocyanins present in the extract, such as delphine galactoside, cyanidin arabinoside, and cyanidin glucoside. We also believe that these findings may provide a reliable basis for developing natural plant drugs to compensate for the side effects of purified and/or chemically synthesized single-component drugs rather than to compete with them. PMID- 26684614 TI - Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant. AB - Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well tolerated practice. PMID- 26684615 TI - Predicting psychiatric inpatient costs. AB - PURPOSE: A large proportion of mental health costs is inpatient care but little is known about their variation between patients. The aim of this study was to measure and identify the predictors of costs of staff contacts and activities on inpatient wards. METHOD: Inpatients from psychiatric hospital wards in south London were interviewed in 2008 and 2009 and staff contacts and use of activities recorded over a week and costs calculated. Regression analyses identified predictors. RESULTS: Of 334 participants, 78% used activities and 90% had staff contacts. However, 41% reported no nurse contact. Mean staff contact and activity costs were L197 and L30 per week, respectively. Staff contact costs were inversely related to age, and activity costs were higher for patients with higher levels of education. Patient satisfaction was positively associated with both costs. CONCLUSIONS: The costs of self-reported staff contacts and use of activities account for a small amount of total inpatient costs. Patients with higher costs appeared to have higher levels of satisfaction. PMID- 26684616 TI - Body Size Adaptations to Altitudinal Climatic Variation in Neotropical Grasshoppers of the Genus Sphenarium (Orthoptera: Pyrgomorphidae). AB - Altitudinal clines in body size can result from the effects of natural and sexual selection on growth rates and developing times in seasonal environments. Short growing and reproductive seasons constrain the body size that adults can attain and their reproductive success. Little is known about the effects of altitudinal climatic variation on the diversification of Neotropical insects. In central Mexico, in addition to altitude, highly heterogeneous topography generates diverse climates that can occur even at the same latitude. Altitudinal variation and heterogeneous topography open an opportunity to test the relative impact of climatic variation on body size adaptations. In this study, we investigated the relationship between altitudinal climatic variation and body size, and the divergence rates of sexual size dimorphism (SSD) in Neotropical grasshoppers of the genus Sphenarium using a phylogenetic comparative approach. In order to distinguish the relative impact of natural and sexual selection on the diversification of the group, we also tracked the altitudinal distribution of the species and trends of both body size and SSD on the phylogeny of Sphenarium. The correlative evidence suggests no relationship between altitude and body size. However, larger species were associated with places having a warmer winter season in which the temporal window for development and reproduction can be longer. Nonetheless, the largest species were also associated with highly seasonal environments. Moreover, large body size and high levels of SSD have evolved independently several times throughout the history of the group and male body size has experienced a greater evolutionary divergence than females. These lines of evidence suggest that natural selection, associated with seasonality and sexual selection, on maturation time and body size could have enhanced the diversification of this insect group. PMID- 26684617 TI - Efficacy of silicate-substituted calcium phosphate with enhanced strut porosity as a standalone bone graft substitute and autograft extender in an ovine distal femoral critical defect model. AB - A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender. PMID- 26684618 TI - De Novo Assembly of Coding Sequences of the Mangrove Palm (Nypa fruticans) Using RNA-Seq and Discovery of Whole-Genome Duplications in the Ancestor of Palms. AB - Nypa fruticans (Arecaceae) is the only monocot species of true mangroves. This species represents the earliest mangrove fossil recorded. How N. fruticans adapts to the harsh and unstable intertidal zone is an interesting question. However, the 60 gene segments deposited in NCBI are insufficient for solving this question. In this study, we sequenced, assembled and annotated the transcriptome of N. fruticans using next-generation sequencing technology. A total of 19,918,800 clean paired-end reads were de novo assembled into 45,368 unigenes with a N50 length of 1,096 bp. A total of 41.35% unigenes were functionally annotated using Blast2GO. Many genes annotated to "response to stress" and 15 putative positively selected genes were identified. Simple sequence repeats were identified and compared with other palms. The divergence time between N. fruticans and other palms was estimated at 75 million years ago using the genomic data, which is consistent with the fossil record. After calculating the synonymous substitution rate between paralogs, we found that two whole-genome duplication events were shared by N. fruticans and other palms. These duplication events provided a large amount of raw material for the more than 2,000 later speciation events in Arecaceae. This study provides a high quality resource for further functional and evolutionary studies of N. fruticans and palms in general. PMID- 26684619 TI - Comparative Analysis of Prokaryotic Communities Associated with Organic and Conventional Farming Systems. AB - One of the most important challenges in agriculture is to determine the effectiveness and environmental impact of certain farming practices. The aim of present study was to determine and compare the taxonomic composition of the microbiomes established in soil following long-term exposure (14 years) to a conventional and organic farming systems (CFS and OFS accordingly). Soil from unclared forest next to the fields was used as a control. The analysis was based on RT-PCR and pyrosequencing of 16S rRNA genes of bacteria and archaea. The number of bacteria was significantly lower in CFS than in OFS and woodland. The highest amount of archaea was detected in woodland, whereas the amounts in CFS and OFS were lower and similar. The most common phyla in the soil microbial communities analyzed were Proteobacteria (57.9%), Acidobacteria (16.1%), Actinobacteria (7.9%), Verrucomicrobia (2.0%), Bacteroidetes (2.7%) and Firmicutes (4.8%). Woodland soil differed from croplands in the taxonomic composition of microbial phyla. Croplands were enriched with Proteobacteria (mainly the genus Pseudomonas), while Acidobacteria were detected almost exclusively in woodland soil. The most pronounced differences between the CFS and OFS microbiomes were found within the genus Pseudomonas, which significantly (p<0,05) increased its number in CFS soil compared to OFS. Other differences in microbiomes of cropping systems concerned minor taxa. A higher relative abundance of bacteria belonging to the families Oxalobacteriaceae, Koribacteriaceae, Nakamurellaceae and genera Ralstonia, Paenibacillus and Pedobacter was found in CFS as compared with OFS. On the other hand, microbiomes of OFS were enriched with proteobacteria of the family Comamonadaceae (genera Hylemonella) and Hyphomicrobiaceae, actinobacteria from the family Micrococcaceae, and bacteria of the genera Geobacter, Methylotenera, Rhizobium (mainly Rhizobium leguminosarum) and Clostridium. Thus, the fields under OFS and CFS did not differ greatly for the composition of the microbiome. These results, which were also confirmed by cluster analysis, indicated that microbial communities in the field soil do not necessarily differ largely between conventional and organic farming systems. PMID- 26684620 TI - Profilin desensitization: A case series. AB - The role of profilin as an allergen has long been questioned. The capacity of profilin to induce respiratory symptoms has recently been demonstrated; moreover, over 50% of patients sensitized to profilin experienced symptoms after the ingestion of plant-derived foods, suggesting that profilin should be considered as a clinically relevant food allergen.We describe the cases of seven allergic patients with oral allergy syndrome and other adverse reactions after eating plant-derived food, that have been undergone to profilin desensitization treatment.The protocol started with a drop of profilin solution (50 ug/mL) diluted 1:10(18) in water until the highest dose of 10 drops of undiluted solution three times a week. At the end of the treatment we observed a decreased mean diameter of profilin wheal in skin prick test (SPT) in five of the seven participants and in profilin specific IgE values in six patients that repeated the test. Regarding basophil activation test (BAT) and the detection of IgG4, we do not have significant results because the tests have to be repeated in some patients. Regarding the double-blind placebo-controlled challenges, after about 10 months of induction phase all the patients showed tolerance to several foods that they previously did not tolerate.Moreover, the immunotherapy with profilin has proved to be safe because no serious adverse events have been reported in our patients.In summary, the results of this exploratory study of sublingual immunotherapy (SLIT) for profilin allergy show that it can be a promising therapeutic option that could modify the clinical reactivity of the patients to the intake of plant-derived food. PMID- 26684621 TI - Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats. AB - Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes. PMID- 26684622 TI - Digital ulcers in scleroderma patients: A retrospective observational study. AB - BACKGROUND: The guidelines for digital ulcers (DUs) management in systemic sclerosis (SSc) indicate the use of iloprost to induce wound healing and bosentan to prevent the onset of new DU. The aim of our study was to evaluate whether the combination treatment may surmount the effect of the single drug. METHODS: We analyzed data regarding 34 patients with SSc and at least one active DU persisting despite 6 months of iloprost therapy, and treated for other 6 months with a combination therapy, i.e. iloprost plus bosentan. RESULTS: Overall, patients initially presented 69 DUs (58 on the fingers and 11 on the legs). At the end of the study 34 (49.3%) DUs were completely healed (responding, R), 18 (26.1%) started the healing process (partially responding, PR), and 17 (24.6%) did not respond (NR) to therapy. No new DU was recorded and the ulcers localized on the legs did not respond to the combination therapy. Finally, data have been analyzed by dividing the patients in two groups according to the fibrosis level on the finger. In the group with mild fibrosis, 83.4% of DUs resulted with showing complete healing while, in the group with severe fibrosis, only 18% of DUs were healed (P = 0.024). CONCLUSION: The treatment with iloprost plus bosentan is effective in determining healing of DUs in SSc patients with mild digital skin fibrosis. Conversely, the severity of skin fibrosis strongly influences the healing process of DUs. The study confirmed the efficacy of bosentan to prevent onset of new DUs. PMID- 26684623 TI - Yiqi Wenyang Fang ameliorates allergic rhinitis through inhibiting inflammatory response and promoting the expression of Foxp3. AB - Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided into six groups (normal control, model control, YWF at low dose, YWF at median dose, YWF at high dose, and loratadine). Rats were injected with antigen for sensitization. Then, rats in the YWF groups were treated with different dose of YWF for 28 days. Loratadine was used as a positive control. Number of sneezes, degree of runny nose, nasal rubbing movements, and tissue damage were scored. The protein and mRNA expression of Foxp3 were determined by western blot and real time-PCR analysis, respectively. Flow cytometry was used to detect the number of CD4+CD25+Foxp3+ Treg cells. The content of interleukin (IL)-10, transforming growth factor beta1 (TGF-beta1), IL-13, and IL-4 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Scores of symptoms were significantly reduced and nasal mucosa damage was alleviated after YWF administration. YWF increased the expression of Foxp3, IL-10, TGF-beta1, and number of CD4+CD25+Foxp3+ Treg cells which were reduced by antigen injection. The expression levels of IL-13 and IL-4 were increased after antigen administration while decreased after YWF treatment. YWF may ameliorate AR through inhibiting inflammatory response and promoting Foxp3 expression. PMID- 26684624 TI - Impact of reactive oxygen species on antioxidant capacity of male reproductive system. AB - The present research work was aimed to study the mutual interaction of reactive oxygen species (ROS) and basal cells antioxidant capacity in the male reproductive system and to further establish the association between selected heavy metals and stress markers. Total oxidant status (TOS) and total antioxidant status (TAS) of serum and seminal plasma were determined by automated photometric methods. The concentrations of Selenium (Se), Lead (Pb), and Cadmium (Cd) were determined by using atomic absorption spectrophotometer. The TOS was increased significantly (P <0.05) in seminal plasma as well as in the serum of the infertile group when compared with the fertile group. On the other hand, the TAS of the infertile group was found to be noticeably decreased (P <0.05) when compared with the TAS of the fertile group. Among the heavy metals, a noticeably lower concentration of Se was detected in the infertile group whereas markedly elevated levels of Cd and Pb were observed in the infertile group compared with the fertile group. Among the infertile group a significant inverse correlation (r = -0.521, P <0.05) was observed between Se and TOS and between Cd and Pb (r = 0.407, P <0.05). Contrarily among the infertile group a considerable positive relationship was established between Se and TAS (r = 0.507, P <0.05). It was concluded that the oxidant stress reduces the antioxidant activity in infertile men by elevating the production of ROS. A lower concentration of Se and elevated levels of Pb and Cd explain the individual's exposure to these heavy metals. The study also revealed that the heavy metal toxicity contributes significantly to male infertility. PMID- 26684625 TI - Endothelial immunomediated reactivity in acute cardiac ischaemia: Role of endothelin 1, interleukin 8 and NT-proBNP in patients affected by unstable angina pectoris. AB - The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs. PMID- 26684627 TI - Evaluation of an oral appliance in patients with mild to moderate obstructive sleep apnea syndrome intolerant to continuous positive airway pressure use: Preliminary results. AB - Obstructive sleep apnea syndrome (OSAS) is a phenomenon of repeated, episodic reduction, or cessation of airflow (hypopnea/apnea) as a result of upper airways obstruction. First-line treatment in younger children is adenotonsillectomy, although other available treatment options in middle-aged adults include continuous positive airways pressure (CPAP) and airway adjuncts. Oral appliances (OA) are a viable treatment alternative in patients with OSAS.The objective of this study was to assess, in a 1-year follow-up study, an OA in OSAS patients. The participants were subjected to polysomnographic examination with a validated device (MicroMESAM). Eight participants were fitted with a Thornton Adjustable Positioner (TAP). The participants were asked to wear the test appliance for 7 nights, and in case of compliance, for 6 months. The selected patients record their usage of the appliance and any adverse effects in a treatment journal. The research focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index) and the effect of oral appliances on daytime function.In conclusion, the results suggest that OA have a definite role in the treatment of snoring and sleep apnea. PMID- 26684626 TI - Epigenetic silencing of endothelin-3 in colorectal cancer. AB - Endothelins are expressed in a variety of human tissue and are involved in the processes as proliferation, migration and differentiation. The signal transduction pathway is a result of the endothelin-1-3 (ET1-3) binding to their receptors (ETAR, ETBR). ET-3 is a new candidate tumour suppressor gene, which is often downregulated or silenced in human cancer.The aim of the study was to examine DNA methylation of ET-3 genes in colorectal cancer (CRC) tissue samples in relation to the clinical stage (CS) of cancer. The paper is a continuation of our previously published results, which showed a four-fold transcriptional silencing of the ET-3 gene in the samples of colorectal cancer in comparison to normal tissues.A total of 66 paired CRC and normal (surgical margin) tissue samples were used in the study. The tumour tissues were collected from CRC patients in CS I-IV according the 7th edition of UICC TNM Classification of Malignant Tumours (CS I, n = 8; CS II, n = 20; CS III, n = 27; CS IV, n = 11). Assessment of epigenetic silencing of the ET-3 encoding gene was performed in three steps. The silencing of the ET-3 encoding gene was a result from methylation of the promoter sequence using methylation-specific PCR (MS-PCR). Analyses were performed using primers complementary for a CpG island in the first exon of the gene encoding ET-3. An epigenetic silence through methylation of 7.5% (5/66) in comparison to control was observed, including 10% of CS II (2/20), 7% of CS III (2/27) and 9% of CS IV (1/11). The controls and the samples of tumour in CS I showed no epigenetic silencing via methylation. In conclusion, epigenetic silencing of ET-3 in CRC could play a role in the progression than in the induction process. EDN3 would be a future target for epigenetic therapy in colorectal cancer, but further clinical studies are needed. PMID- 26684628 TI - New miRNAs network in human mesenchymal stem cells derived from skin and amniotic fluid. AB - Mesenchymal stem cells (MSCs), isolated from different adult sources, have great appeal for therapeutic applications due to their simple isolation, extensive expansion potential, and high differentiative potential.In our previous studies we isolated MSCs form amniotic fluid (AF-MSCs) and skin (S-MSCs) and characterized them according to their phenotype, pluripotency, and mRNA/microRNAs (miRNAs) profiling using Card A from Life Technologies.Here, we enlarge the profiling of AF-MCSs and S-MSCs to the more recently discovered miRNAs (Card B by Life Technologies) to identify the miRNAs putative target genes and the relative signaling pathways. Card B, in fact, contains miRNAs whose role and target are not yet elucidated.The expression of the analyzed miRNAs is changing between S MSCs and AF-MSCs, indicating that these two types of MSCs show differences potentially related to their source. Interestingly, the pathways targeted by the miRNAS deriving from Card B are the same found during the analysis of miRNAs from Card A.This result confirms the key role played by WNT and TGF-beta pathways in stem cell fate, underlining as other miRNAs partially ignored up to now deserve to be reconsidered. In addition, this analysis allows including Adherens junction pathways among the mechanisms finely regulated in stem cell behavior. PMID- 26684629 TI - CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-gamma) and Th2 (CCR4, IL 4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies characterized by decreased serum immunoglobulin G along with a decrease in serum IgA and/or IgM, defective specific antibody production, and recurrent bacterial infections. Abnormal lymphocyte trafficking, dysregulated cellular responses to chemokines, and uncontrolled T cell polarization may be involved in the pathogenesis and may help to understand the clinical complications. We evaluated T helper cell subsets (chemokine receptors CCR4, CCR5, and CCR7), expressions on T lymphocytes, intracellular cytokines - IL-2, IL 4, IL-13, IFN- gamma-on CD4(+) T cells, and expression of CD4(+)CD25(+)Foxp3(+) regulatory T cells of 20 CVID patients and 26 healthy controls. Autoimmune clinical findings and other complications were also determined. Percentages and absolute numbers of CD4(+)CD25(+) Foxp3(+) cells did not show any significant difference between CVID cases and healthy controls nor between severe and moderate disease patients. The only significant difference regarding Th1 and Th2 type intracellular cytokines was the decreased absolute numbers of CD3(+)CD4(+)IL4(+) cells in CVID cases. There were some findings about T helper cell type dominance in CVID patients such as positive correlation between hepatomegaly and high IL-2 and IFN-gamma in CD3(+)CD4(+) cells and very high expression of CCR5 (Th1) on CD3(+)CD4(+) cells in patients with granuloma. Th1 (CCR5) and Th2 (CCR4) type chemokine receptors did not show any dominance in CVID cases. However, frequencies of CCR7 expressing CD3(+) T cells, CD3(+)CD4(+) T helper cells and CD3(+)CD8(+) T cytotoxic cells were significantly lower in severe CVID patients. In addition, presence of autoimmune clinical findings was negatively correlated with CCR7(+) cells. As CCR7 is a key mediator balancing immunity and tolerance in the immune system, the abnormality of this mediator may contribute to the profound immune dysregulation seen in CVID. In addition, Th1 cells seem to be more involved in the disease pathogenesis than Th2 cells. PMID- 26684630 TI - Plasma total thiol pool in children with asthma: Modulation during montelukast monotherapy. AB - BACKGROUND: Inflammation, which is a hallmark of asthma, is one of the main sources of oxidative stress in the human body. Thiols are powerful antioxidants that protect cells against the consequences of oxidative stress. We aimed to investigate whether asthma and montelukast monotherapy affect the total plasma thiol pool in children. METHODS: A total of 60 children with asthma and 35 healthy controls participated in the study. Group I consisted of newly diagnosed asthmatics who did not have regular anti-asthmatic therapy previously. Group II consisted of patients who had been undertaking montelukast monotherapy regularly for at least 4 months. Plasma total antioxidant status (TAS) and plasma total thiol (PTT) were measured using spectrophotometric methods. RESULTS: Bronchial asthma patients in both groups I and II had decreased median TAS levels compared with the control group (1.59 [interquartile range, 1.04-1.70] and 1.67 [1.50 1.75] vs. 2.98 [2.76-3.16] Trolox equiv./L, respectively; P<0.001). Group I had decreased PTT concentrations compared with the control group (0.18 [0.16-0.20] vs. 0.21 [0.19-0.22] mmol/L; P<0.001), and group II had similar PTT levels to the control group (0.20 [0.17-0.22] mmol/L; P>0.05). In addition, the median TAS and PTT levels for groups I and II were not statistically different (P>0.05). There was a positive correlation between TAS and PTT levels (rho=0.38, P<0.05) in group I. CONCLUSION: In order to balance the oxidative stress, both TAS and PTT which are markers of the antioxidant system are reduced in children with asthma. Montelukast monotherapy can limit oxidative stress and thus restore PTT levels but not TAS levels in asthmatic children. PMID- 26684631 TI - Allopurinol-induced Sweet's syndrome. AB - Sweet's syndrome, or acute febrile neutrophilic dermatosis, is an uncommon severe cutaneous condition, not previously associated with allopurinol therapy. We describe the case of an 87-year-old woman with hyperuricemia who developed classic Sweet's syndrome manifestations 8 days after being treated with allopurinol. Patient's symptoms included fever, painful edema in the hands and lower limbs with non-pruritic erythematous plaques topped by pus-filled skin blisters, right eye conjunctivitis, splenomegaly and joint pain. At the emergency department, blood tests showed neutrophilic leukocytosis, inflammatory state and altered liver function. During hospitalization, she received unsuccessful treatments with two different antibiotics (namely ceftriaxone and levofloxacin), while treatment with intravenous methylprednisolone produced a rapid clinical remission of symptoms, cutaneous lesion pain improvement, normalization of her body temperature and her blood values returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of Sweet's syndrome and allopurinol therapy. Because the signs and symptoms of Sweet's syndrome resemble an infectious process, the correct diagnosis may be delayed and inappropriate treatment regimen with antibiotics may often precede glucocorticoid therapy. PMID- 26684632 TI - Genetic polymorphisms and the development of invasive bacterial infections in children. AB - To evaluate the associations between single nucleotide polymorphisms (SNPs) of factors involved in the development of invasive bacterial disease (IBD) in children, 47 SNPs of 18 candidate genes were analysed in 49 children with IBD and 100 controls. The G/T genotype of TLR2 rs2149356 and the C genotype of LTA rs2229094 were associated with significantly reduced risk of developing IBD (P=0.04 and P=0.05, respectively), whereas the C/T genotype of RFP175 rs1585110 was associated with a significantly higher risk of developing IBD (P=0.02). These results support the evidence that some genetic variants of factors involved in innate immunity may influence IBD risk in children. PMID- 26684634 TI - Caffeine affects CD8+ lymphocyte apoptosis and migration differently in naive and familiar individuals following moderate intensity exercise. AB - The purpose of this investigation was to determine the lymphocyte subset response to 30 min of moderate treadmill exercise during caffeine supplemented (6.0 mg.kg( 1)) and placebo conditions in caffeine-naive and -familiar individuals. Seventeen individuals participated (caffeine-familiar = 8, caffeine-naive = 9) completing two exercise bouts (caffeine supplemented and placebo control) 48 h apart in a counterbalanced and double-blinded fashion. Individuals were classified as follows: caffeine-naive <50 mg.d(-1) and caffeine-familiar >200 mg.d(-1) Whole blood samples were obtained at rest, 30 min after caffeine or placebo ingestion, immediately following exercise, and 1 h post exercise. Blood was used to analyze apoptosis (annexin V) and cellular migration (CX3CR1) responses in lymphocyte subsets (CD4+, CD8+, CD19+). Absolute changes from rest values were calculated and differences between conditions were determined through Chi-squared analysis with significance accepted at P <0.05. With regard to CD4+ and CD19+ lymphocytes, the interaction of caffeine and exercise did not affect naive individuals to a greater extent immediately post exercise when compared to familiar, as similar apoptotic and migratory responses were observed (P >0.05). However, CD8+ lymphocyte cell death and migration responses were observed to be significantly greater at each sampling point in caffeine-familiar individuals (P <0.05). It is possible that chronic caffeine supplementation may prime CD8+ cell receptors for responsiveness to apoptosis and migration and the consequence of this form of immunosuppression in the post-exercise period should be determined. PMID- 26684633 TI - Safety and efficacy of intra-articular anti-tumor necrosis factor alpha agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare. AB - The aim of this study was to assess safety and efficacy of ultrasonography (US) guided intra-articular injections using tumor necrosis factor (TNF) blockers compared to corticosteroids in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients, experiencing refractory monoarthritis despite the current systemic therapy. Eighty-two patients were randomized to receive three intra articular injections monthly of either corticosteroid or TNF blockers. Primary endpoints were the safety and an improvement greater than 20% for visual analogic scales of involved joint pain in patients injected with anti-TNFalpha. Further clinical, US, and magnetic resonance imaging (MRI) evaluations were considered secondary endpoints. Intra-articular TNF blockers are a safe strategy, determining a significant reduction of patient and physician reported clinical outcomes and US/MRI scores, in RA and PsA patients, when compared to intra articular injections of corticosteroids. US guidance excluded the possibility to inject the drug in the wrong site, maximizing local effects, reducing systemic effects, and increasing the safety of the procedure. Patients with inflammatory monoarthritis could be successfully treated with US-guided intra-articular TNF blockers that are a safe and well tolerated procedure, to achieve a longstanding clinical and radiological good clinical response and/or disease remission. PMID- 26684635 TI - Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial. AB - Until now glucosamine sulfate (GS) has been the most widely used supplement and has been shown to be efficacious in the treatment of osteoarthritis (OA). Methylsulfonylmethane (MSM) and boswellic acids (BA) are new effective supplements for the management of inflammation and joint degeneration, according to previous experimental studies. The aim of our study is to test the effectiveness of association of MSM and BA in comparison with GS in knee arthritis.In this prospective randomized clinical trial, MEBAGA (Methylsulfonylmethane and Boswellic Acids versus Glucosamine sulfate in the treatment of knee Arthritis), 120 participants affected by arthritis of the knee were randomly assigned to an experimental group (MB group) or a control group (GS group) treated for 60 days with 5 g of MSM and 7.2 mg of BA or with 1500 mg of GS daily, respectively. At the 2-month (T1) and 6-months (T2) follow-up , the efficacy of these two nutraceuticals was assessed using the visual analog pain scale (VAS) and the Lequesne Index (LI) for joint function, along with the use of anti-inflammatory drugs (non-steroidal anti-inflammatory drugs and anti cyclooxygenase-2).The repeated measures ANOVA analysis shows that for VAS, LI, and the use of anti-inflammatory drugs scores there are improvements due to the time in the two groups (respectively, F=26.0; P<0.0001; F=4.15; P=0.02; F=3.38; P=0.04), with a tendency to better values for the MB group at T2.On the basis of these preliminary data, we could support the efficacy of the MSM in association with BA in the treatment of OA. These results are consistent with the anti inflammatory and chondroprotective effects previously occurred in experimental studies. This new combination of integration (MSM and BS) has presented good results and satisfactory in comparison with GS, until now the cornerstone of the treatment of arthritis in according to guidelines. PMID- 26684636 TI - Expression of IL-17A concentration and effector functions of peripheral blood neutrophils in food allergy hypersensitivity patients. AB - Lymphocytes Th17 and other types of immune system cells produce IL17. By induction of cytokines and chemokines, the IL17 cytokine is involved in mechanisms of allergic reaction with participation of neutrophil granulocytes. It affects activation, recruitment, and migration of neutrophils to the tissues, regulating inflammatory reaction intensity. Excited neutrophils secrete inter alia elastase and reactive oxygen species (ROS)--significant mediators of inflammation process responsible for tissues damage.The aim of the study was to evaluate the concentrations of serum interleukin 17A, serum neutrophil elastase, and ROS production by neutrophils in patients with food allergy.The study included 30 patients with food allergy diagnosed based on interview, clinical symptoms, positive SPT, placebo controlled double-blind oral provocation trial, and the presence of asIgE in blood serum against selected food allergens using fluoro-immuno-enzymatic method FEIA UNICap 100. The control group consisted of 10 healthy volunteers. The concentrations of IL17A were determined in all patients using ELISA method with eBioscience kits, and elastase using BenderMed Systems kits. Chemiluminescence of non-stimulated neutrophils was evaluated using luminol dependent kinetic method for 40 min on Luminoskan (Labsystems luminometer).The results of serum IL-17A concentrations and the values of chemiluminescence obtained by non-activated neutrophils, as well as elastase concentrations, were higher in patients with food allergic hypersensitivity compared to healthy volunteers.This study demonstrates a significance of IL-17A and activated neutrophil granulocytes in the course of diseases with food allergic hypersensitivity. PMID- 26684637 TI - Clinic manifestations in granulomatosis with polyangiitis. AB - Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis (WG), is an uncommon immunologically mediated systemic small-vessel vasculitis that is pathologically characterised by an inflammatory reaction pattern (necrosis, granulomatous inflammation and vasculitis) that occurs in the upper and lower respiratory tracts and kidneys. Although the aetiology of GPA remains largely unknown, it is believed to be autoimmune in origin and triggered by environmental events on a background of genetic susceptibility.In Europe, the prevalence of GPA is five cases per 100,000 population, with greater incidence in Northern Europe. GPA can occur in all racial groups but predominantly affects Caucasians. Both sexes are affected equally. GPA affects a wide age range (age range, 8-99 years).Granulomatosis with polyangiitis is characterised by necrotising granulomatous lesions of the respiratory tract, vasculitis and glomerulonephritis. Classically, the acronym ELK is used to describe the clinical involvement of the ear, nose and throat (ENT); lungs; and kidneys. Because the upper respiratory tract is involved in 70-100% of cases of GPA, classic otorhinolaryngologic symptoms may be the first clinical manifestation of disease. The nasal cavity and the paranasal sinuses are the most common sites of involvement in the head and neck area (85-100%), whereas otological disease is found in approximately 35% (range, 19-61%) of cases.Diagnosis of GPA is achieved through clinical assessment, serological tests for anti-neutrophil cytoplasmic antibodies (ANCA) and histological analysis. The 10-year survival rate is estimated to be 40% when the kidneys are involved and 60-70% when there is no kidney involvement.The standard therapy for GPA is a combination of glucocorticoids and cyclophosphamide. In young patients, cyclophosphamide should be switched to azathioprine in the maintenance phase.A multidisciplinary approach, involving otorhinolaryngologists, oral and maxillofacial surgeons, oral physicians, rheumatologists, renal and respiratory physicians, and ophthalmologists, is necessary for the diagnosis and therapeutic treatment of GPA. ENT physicians have a determining role in recognising the early onset of the disease and starting an appropriate therapy. PMID- 26684638 TI - Sea buckthorn (Hippophae rhamnoides L.) oil protects against chronic stress induced inhibitory function of natural killer cells in rats. AB - Chronic stress can suppress natural killer (NK) cell activity; this may also be related to the effect of stress on the neuroendocrine-immune network. Sea buckthorn (SBT) (Hippophae rhamnoides L.) is a thorny nitrogen fixing deciduous shrub, native to both Europe and Asia. It has been used as a medicinal plant in Tibetan and Mongolian traditional medicines. SBT has multifarious medical properties, including anti-fatigue as well as immunoregulatory effects. This study reports the effects of SBT oil with regard to the cytotoxicity and quantity of NK cells in the blood of a chronic-stress rat model, in addition to its mechanisms on the neuroendocrine-immune network. These results show that SBT oil, given by gavage to rats with chronic stress, could increase the following: body weight, NK cell quantities, and cytotoxicity, as well as the expression of perforin and granzyme B. The results also show that SBT oil in rats with chronic stress could suppress cortisol, ACTH, IL-1beta and TNF-alpha levels, in addition to increasing 5-HT and IFN-gamma serum levels. This leads to suggest that SBT oil, in rats with chronic stress, can increase NK cell cytotoxicity by upregulating the expression of perforin and granzyme B, thus causing associated effects of SBT oil on the neuroendocrine-immune network. PMID- 26684639 TI - Immunotoxicological impact of occupational and environmental nanoparticles exposure: The influence of physical, chemical, and combined characteristics of the particles. AB - While nanotechnology is growing exponentially, the knowledge of the impact of nanoparticles (NPs) on public health and the environment is limited so far. Current nanomaterial research is focused on the applications of nanotechnology, whereas there is little information on exposure assessment and risk characterization associated with NPs. Therefore, it is essential that the factors influencing NPs associated hazards be studied. This review seeks to survey and evaluate the current literature in order to better understand the impact of both airborne and engineered NPs exposure, the mechanisms at the cellular level, and the factors influencing their immunotoxicity. In fact, NPs do have immunotoxicological significance, as immune cells in the bloodstream and tissues do act to eliminate or interact with NPs.Proper characterization of the NPs as well as understanding the processes occurring on the NPs surface when in contact with biological systems is crucial to predict or exclude toxicological effects. PMID- 26684640 TI - Heterogeneity in the genetic alterations and in the clinical presentation of acrodermatitis enteropathic: Case report and review of the literature. AB - Acrodermatitis enteropathic (AE) is a rare autosomal recessive disorder due to a zinc deficiency and characterized by a classical triad of symptoms: dermatitis, alopecia, and diarrhea. The defective gene is SLC39A4, which encodes a zinc transporter. Nevertheless many abnormalities in SLC39A4 have been relieved, only 50% of patients show alterations. Here is reported the case of an infant with mild and incomplete manifestations of AE, for whom the SLC39A4 genetic test was performed. A novel mutation in SLC39A4 was identified. Zinc replacement improved rapidly the skin lesions. Our case highlights the importance of suspecting this rare condition and to perform the genetic test even in those patients who do not fulfil the classical triad of symptoms. Further efforts should be addressed to identify a more strength correlation between genotype and phenotype of this disorder. PMID- 26684641 TI - Synergic development of pharmacokinetics and bioanalytical methods as support of pharmaceutical research. AB - The development of pharmacokinetics led this science to achieve a relevant role in the investigation of new chemical entities for therapeutic application, and has allowed a series of new useful realizations of out of patent drugs like prolonged release and delayed release formulations, therapeutic delivery system (TDS) for drugs to be active in systemic circulation avoiding the first pass effect, orodispersible and effervescent formulations, intramuscular and subcutaneous depot formulations acting over a long period, oral inhalatory systems, and drug association at fixed dose. The above applications had pharmacokinetics as protagonist and have required the support from bioanalytical methods to assay drug concentrations, even in pg.mL(-1) of plasma, that really have paralleled the synergic development of pharmacokinetics.The complexity of the above realizations required specific guidelines from the regulatory authorities, mainly the US FDA and EU EMA, which have normalized and, in most cases, simplified the above applications admitting some waivers of in vivo bioequivalence.However, this review highlights some critical points, not yet focused on by operating guidelines, which need to be clarified by regulatory authorities. One of the most relevant issues is about the planning and conducting bioavailability and bioequivalence trials with endogenous substances, that possess own homeostatic equilibria with fluctuations, in some cases with specific rhythms, like melatonin and female sex hormones. The baseline subtraction required by guidelines to define the net contribute to the exogenous absorbed drug in most cases is a non-solvable problem. PMID- 26684642 TI - Bullous pemphigoid in infant post vaccination: Myth or reality? AB - Bullous pemphigoid is rare in children and even rarer in infants. By presenting two cases of bullous pemphigoid related by their temporal proximity with a previous episode of vaccination, it will be carefully discussed if a relationship is or is not possible. Our final conclusion is that the association is mostly a myth rather than a reality and bullous pemphigoid is not a contraindication to continue with the normal vaccination schedule of infants. It is important to know about this clinical entity in order to perform adequate treatment that avoids any worsening or future relapse of this disease. PMID- 26684644 TI - 5th International ACC Symposium: Imaging for Diagnosis and Surveillance of Adrenal Tumors--New Advances and Reviews of Old Concepts. AB - Adrenocortical carcinoma (ACC) is often diagnosed incidentally. However, significant difficulties persist in diagnosing the rare ACC among the very common benign adrenal tumors, which are present in up to 5% of the population. Due to the very low prevalence of ACC, prospective studies are impossible to conduct. Two recent studies took the approach of reviewing preexisting adrenal tumors prior to the diagnosis of ACC. These data challenge current concepts of diagnosis and surveillance of incidentally discovered masses. Oncocytomas (benign and malignant) represent an entity that can be difficult to be diagnosed by radiographic characteristics and even histologically. However, some recent data provides insight into their appearance in imaging procedures. With regards to ACC specific imaging, which could be applied for differential diagnosis of adrenal tumors, surgery planning and surveillance several radionucleotides have been evaluated over the last decades showing promising results. Of particular interest, these substances can potentially be used for therapy as well. PMID- 26684643 TI - Is the irradiated small bowel volume still a predictor for acute lower gastrointestinal toxicity during preoperative concurrent chemo-radiotherapy for rectal cancer when using intensity-modulated radiation therapy? AB - BACKGROUND: The small bowel (SB) represents the most important dose-limiting structure in pelvic radiotherapy (RT). However, we observed that the majority of rectal cancer patients who received preoperative pelvic intensity modulated RT (IMRT) developed acute tenesmus without watery diarrhea. The objective of this study is to determine if the RT dose to SB affects the acute lower gastrointestinal toxicity (ALGIT) in rectal cancer patients who received neoadjuvant concurrent chemotherapy-IMRT. We will also evaluate if patient and tumor factors affect the ALGIT. METHODS: We retrospectively analyzed 63 rectal cancer patients that consecutively received preoperative IMRT (45 Gy for pelvis and 50 Gy for gross tumor in 25 fractions) with concurrent chemotherapy (oxaliplatin 130 mg/m(2) on day 1 and capecitabine 825 mg/m(2), twice per day from day 1 to day 14, week 1 and 4) between May 2012 and May 2013. The ALGIT was assessed with Common Terminology Criteria for Adverse Events version 3. The patients were stratified into two groups (with and without grade >=2 ALGIT). The effect of SB volume receiving 5 to 40 Gy (V5 to V40) at a 5 Gy interval dose level on grade >=2 ALGIT was evaluated. The volume of small bowel is defined as the volume of the small bowel loop. Other factors evaluated include patient's age and gender, tumor size and location and preexisting number of daily bowel movements. RESULTS: Overall, grade >=2 ALGIT occurred in 57 % (36/63) patients. There was no significant difference between the two groups of patients (with and without grade >=2 ALGIT) in SB V5 to V40, patient's age and gender, tumor location and preexisting number of daily bowel movements. There was a significant difference between the two groups of patients in tumor volume (with grade >=2 ALGIT: 115.5 +/- 85.5 cm(3) versus without grade >=2 ALGIT: 58.5 +/- 25.2 cm(3), p = 0.0001). Multivariate analysis revealed no association between the dose SB received (V5 to V40) and the grade >=2 ALGIT after adjusting for the tumor volume. CONCLUSIONS: With IMRT technique used in rectal cancer patients undergoing preoperative chemo-radiotherapy, the acute lower GI toxicity is not associated with small bowel V5 to V40; instead it is associated with rectal tumor size. PMID- 26684645 TI - 5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer. AB - Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland. PMID- 26684647 TI - Potentiation of Neuronal Nicotinic Receptors by 17beta-Estradiol: Roles of the Carboxy-Terminal and the Amino-Terminal Extracellular Domains. AB - The endogenous steroid 17beta-estradiol (betaEST) potentiates activation of neuronal nicotinic receptors containing alpha4 subunits. Previous work has shown that the final 4 residues of the alpha4 subunit are required for potentiation. However, receptors containing the alpha2 subunit are not potentiated although it has these 4 residues, and only one amino acid difference in the C-terminal tail (FLAGMI vs. WLAGMI). Previous work had indicated that the tryptophan residue was involved in binding an analog of betaEST, but not in potentiation by betaEST. To determine the structural basis for the loss of potentiation we analyzed data from chimeric subunits, which indicated that the major factor underlying the difference between alpha2 and alpha4 is the tryptophan/phenylalanine difference, while the N-terminal extracellular domain is a less significant factor. When the tryptophan in alpha4 was mutated, both phenylalanine and tyrosine conferred lower potentiation while lysine and leucine did not. The reduction reflected a reduced maximal magnitude of potentiation, indicating that the tryptophan is involved in transduction of steroid effects. The regions of the alpha4 N-terminal extracellular domain involved in potentiation lie near the agonist-binding pocket, rather than close to the membrane or the C-terminal tail, and appear to be involved in transduction rather than binding. These observations indicate that the C-terminal region is involved in both steroid binding (AGMI residues) and transduction (W). The role of the N-terminus appears to be independent of the C terminal tryptophan and likely reflects an influence on conformational changes caused during channel activation by agonist and potentiation by estradiol. PMID- 26684646 TI - Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection. AB - Staphylococcus aureus is capable of infecting nearly every organ in the human body. In order to infiltrate and thrive in such diverse host tissues, staphylococci must possess remarkable flexibility in both metabolic and virulence programs. To investigate the genetic requirements for bacterial survival during invasive infection, we performed a transposon sequencing (TnSeq) analysis of S. aureus during experimental osteomyelitis. TnSeq identified 65 genes essential for staphylococcal survival in infected bone and an additional 148 mutants with compromised fitness in vivo. Among the loci essential for in vivo survival was SrrAB, a staphylococcal two-component system previously reported to coordinate hypoxic and nitrosative stress responses in vitro. Healthy bone is intrinsically hypoxic, and intravital oxygen monitoring revealed further decreases in skeletal oxygen concentrations upon S. aureus infection. The fitness of an srrAB mutant during osteomyelitis was significantly increased by depletion of neutrophils, suggesting that neutrophils impose hypoxic and/or nitrosative stresses on invading bacteria. To more globally evaluate staphylococcal responses to changing oxygenation, we examined quorum sensing and virulence factor production in staphylococci grown under aerobic or hypoxic conditions. Hypoxic growth resulted in a profound increase in quorum sensing-dependent toxin production, and a concomitant increase in cytotoxicity toward mammalian cells. Moreover, aerobic growth limited quorum sensing and cytotoxicity in an SrrAB-dependent manner, suggesting a mechanism by which S. aureus modulates quorum sensing and toxin production in response to environmental oxygenation. Collectively, our results demonstrate that bacterial hypoxic responses are key determinants of the staphylococcal-host interaction. PMID- 26684648 TI - The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain. AB - INTRODUCTION: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain. DATABASES AND DATA TREATMENT: We searched PUBMED and the Cochrane Library for in vitro and in vivo studies from July 1975 to August 2014. In vitro articles providing an explanation for the mechanisms of action of lidocaine on the neuroinflammatory response in pain were included. Animal or clinical studies were included concerning iv lidocaine for acute or chronic pain or during inflammation. RESULTS: Eighty-eight articles regarding iv lidocaine were included: 36 in vitro studies evaluating the effect on ion channels and receptors; 31 animal studies concerning acute and chronic pain and inflammatory models; 21 clinical studies concerning acute and chronic pain. Low-dose lidocaine inhibits in vitro voltage-gated sodium channels, the glycinergic system, some potassium channels and Galphaq-coupled protein receptors. Higher lidocaine concentrations block potassium and calcium channels, and NMDA receptors. Animal studies demonstrate lidocaine to have analgesic effects in acute and neuropathic pain syndromes and anti-inflammatory effects early in the inflammatory response. Clinical studies demonstrate lidocaine to have advantage in abdominal surgery and in some neuropathic pain syndromes. CONCLUSIONS: Intravenous lidocaine has analgesic, anti-inflammatory and antihyperalgesic properties mediated by an inhibitory effect on ion channels and receptors. It attenuates the neuroinflammatory response in perioperative pain and chronic neuropathic pain. PMID- 26684650 TI - Correction: Notch Signaling Mediates the Age-Associated Decrease in Adhesion of Germline Stem Cells to the Niche. PMID- 26684649 TI - Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis. AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. METHODS: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. RESULTS: Analyses revealed a mutation detection sensitivity of 97.3%, an average coverage per gene of 98.0%, and adequate coverage over 98.6% of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38%). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. CONCLUSIONS: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization. PMID- 26684651 TI - Prevalence, Awareness and Control of Hypertension in Patients with Transient Ischemic Attacks in China. AB - BACKGROUND: Hypertension is a major risk factor for stroke recurrence in patients with transient ischemic attacks (TIAs). The aim of this study was to estimate the prevalence, awareness, treatment and control rates of hypertension in Chinese adults with TIA. METHODS: We analyzed data derived from the 2010 China Chronic Disease and Risk Factor Surveillance survey, a population-based study including a nationally representative sample of 2,780 Chinese adults with TIA. The national prevalence, awareness and control rates of hypertension in adults with TIA were estimated with weighted coefficients based on the 2010 China population census. RESULTS: Among the 2,780 TIA patients, a total of 1,919 patients were identified as having hypertension. The estimated national prevalence of hypertension in TIA patients was 67.5% (95% CI 64.0-71.0). Among the hypertensive patients, 54.1% were aware of having hypertension and 8.3% was under control. CONCLUSIONS: Hypertension is severely under-diagnosed and under-controlled in patients with TIA in China. Appropriate strategies are urgently needed to improve the identification and control of hypertension in these patients. PMID- 26684652 TI - Predicting target proteins for drug candidate compounds based on drug-induced gene expression data in a chemical structure-independent manner. AB - BACKGROUND: Phenotype-based high-throughput screening is a useful technique for identifying drug candidate compounds that have a desired phenotype. However, the molecular mechanisms of the hit compounds remain unknown, and substantial effort is required to identify the target proteins associated with the phenotype. METHODS: In this study, we propose a new method to predict target proteins of drug candidate compounds based on drug-induced gene expression data in Connectivity Map and a machine learning classification technique, which we call the "transcriptomic approach." RESULTS: Unlike existing methods such as the chemogenomic approach, the transcriptomic approach enabled the prediction of target proteins without dependence on prior knowledge of compound chemical structures. The prediction accuracy of the chemogenomic approach was highly depended on compounds structure similarities in data sets. In contrast, the prediction accuracy of the transcriptomic approach was maintained at a sufficient level, even for benchmark data consisting of structurally diverse compounds. CONCLUSIONS: The transcriptomic approach reported here is expected to be a useful tool for structure-independent prediction of target proteins for drug candidate compounds. PMID- 26684653 TI - Participating in a fruit and vegetable intervention trial improves longer term fruit and vegetable consumption and barriers to fruit and vegetable consumption: a follow-up of the ADIT study. AB - BACKGROUND: Fruit and vegetable (FV) based intervention studies can be effective in increasing short term FV consumption. However, the longer term efficacy of such interventions is still unclear. The aim of the current study was to examine the maintenance of change in FV consumption 18-months after cessation of a FV intervention and to examine the effect of participating in a FV intervention on barriers to FV consumption. METHODS: A follow-up of a randomised controlled FV trial in 83 older adults (habitually consuming <=2 portions/day) was conducted. At baseline, participants were assigned to continue consuming <=2 portions FV/day or consume >=5 portions FV/day for 16-weeks. We assessed FV intake and barriers to FV consumption at baseline, end of intervention and 18-months post intervention. RESULTS: At 18-months, mean FV intakes in both groups were greater than baseline. The 5 portions/day group continued to show greater increases in FV consumption at 18-months than the 2 portions/day group (p < 0.01). At 18-months, both groups reported greater liking (p < 0.01) and ease in consuming FV (p = 0.001) while difficulties with consuming FV decreased (p < 0.001). The 2 portions/day group reported greater awareness of FV recommendations at 18-months (p < 0.001). CONCLUSIONS: Participating in a FV intervention can lead to longer term positive changes in FV consumption regardless of original group allocation. TRIAL REGISTRATION: Clinical Trials.gov NCT00858728 . PMID- 26684654 TI - Unexpected Complications Following Adult Medical Male Circumcision Using the PrePex Device. AB - INTRODUCTION: In this study, we describe and depict unexpected sequelae of adult medical male circumcision (MMC) using the PrePex device. MATERIALS AND METHODS: The PrePex system is an elastic compression device for adult MMC. The device is well studied, has been pre-qualified by the World Health Organization (WHO), and its use is being scaled-up in African countries targeted by WHO. We conducted a PrePex implementation study in routine service delivery among 427 men in the age range of 18-49 in western Kenya. We captured penile photographs to create a record of adverse events (AEs) and to monitor healing. Several unexpected AEs ensued, including some that have not been reported in other PrePex studies. We describe and depict those unexpected complications and resulting treatments to alert circumcision providers in the relevant areas. RESULTS: We observed 5 device displacements (1.2%); 3 cases of early sloughing of foreskin tissue (0.7%) among men with long foreskins; 2 cases of a long foreskin obstructing urine flow, as it became dry and necrotic (0.5%); and 2 cases of insufficient foreskin removal caused by invagination for which surgical completion was necessary (0.5%). All of the participants healed completely by day 42 post-circumcision or shortly thereafter. CONCLUSION: The potential for these complications should be incorporated into PrePex training programs. Integration of devices into MMC programs in medically underserved areas requires the availability of prompt surgical intervention for some sequelae, particularly displacement events. PMID- 26684655 TI - Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy. AB - X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma. Recent findings on pathomechanisms of the peroxisomal neurometabolic disease X-ALD have provided important clues on therapeutic targets. Here we describe the impact of chronic redox imbalance caused by the excess VLCFA on mitochondrial biogenesis and respiration, and explore the consequences on the protein quality control systems essential for cell survival, such as the proteasome and autophagic flux. Defective proteostasis, together with mitochondrial malfunction, is a hallmark of the most prevalent neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and of the aging process. Thus, we discuss molecular targets and emerging treatment options that may be common to both multifactorial neurodegenerative disorders and X-ALD. New-generation antioxidants, some of them mitochondrial targeted, mitochondrial biogenesis boosters such as pioglitazone and resveratrol, and the mTOR inhibitor temsirolimus hold promise as disease modifying therapies. PMID- 26684656 TI - Phosphorylation of the C Terminus of RHD3 Has a Critical Role in Homotypic ER Membrane Fusion in Arabidopsis. AB - The endoplasmic reticulum (ER) consists of dynamically changing tubules and cisternae. In animals and yeast, homotypic ER membrane fusion is mediated by fusogens (atlastin and Sey1p, respectively) that are membrane-associated dynamin like GTPases. In Arabidopsis (Arabidopsis thaliana), another dynamin-like GTPase, ROOT HAIR DEFECTIVE3 (RHD3), has been proposed as an ER membrane fusogen, but direct evidence is lacking. Here, we show that RHD3 has an ER membrane fusion activity that is enhanced by phosphorylation of its C terminus. The ER network was RHD3-dependently reconstituted from the cytosol and microsome fraction of tobacco (Nicotiana tabacum) cultured cells by exogenously adding GTP, ATP, and F actin. We next established an in vitro assay system of ER tubule formation with Arabidopsis ER vesicles, in which addition of GTP caused ER sac formation from the ER vesicles. Subsequent application of a shearing force to this system triggered the formation of tubules from the ER sacs in an RHD-dependent manner. Unexpectedly, in the absence of a shearing force, Ser/Thr kinase treatment triggered RHD3-dependent tubule formation. Mass spectrometry showed that RHD3 was phosphorylated at multiple Ser and Thr residues in the C terminus. An antibody against the RHD3 C-terminal peptide abolished kinase-triggered tubule formation. When the Ser cluster was deleted or when the Ser residues were replaced with Ala residues, kinase treatment had no effect on tubule formation. Kinase treatment induced the oligomerization of RHD3. Neither phosphorylation-dependent modulation of membrane fusion nor oligomerization has been reported for atlastin or Sey1p. Taken together, we propose that phosphorylation-stimulated oligomerization of RHD3 enhances ER membrane fusion to form the ER network. PMID- 26684657 TI - Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA. AB - The effects of lysine peptide lengths on DNA and siRNA packaging and delivery were studied using four linear oligolysine peptides with 8 (K8), 16 (K16), 24 (K24) and 32 (K32) lysines. Oligolysine peptides with 16 lysines or longer were effective for stable monodisperse particle formation and optimal transfection efficiency with plasmid DNA (pDNA), but K8 formulations were less stable under anionic heparin challenge and consequently displayed poor transfection efficiency. However, here we show that the oligolysines were not able to package siRNA to form stable complexes, and consequently, siRNA transfection was unsuccessful. These results indicate that the physical structure and length of cationic peptides and their charge ratios are critical parameters for stable particle formation with pDNA and siRNA and that without packaging, delivery and transfection cannot be achieved. PMID- 26684658 TI - Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents. AB - BACKGROUND: In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9-12 years through the existing school based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents' knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent. METHODS: Following vaccine introduction, a cross-sectional telephone survey was conducted with parents of vaccine-eligible girls from randomly selected schools, stratified by educational district. Factors related to vaccine consent were explored using Generalised Estimating Equations. RESULTS: There were 560 vaccine-eligible girls attending the participating 19 schools at the time of the campaign. Among these, 313 parents could be contacted, with 293 agreeing to participate (93.6%). Almost 80% of participants reported having consented to HPV vaccination (230/293, 78.5%). Reported knowledge of cervical cancer and HPV prior to the campaign was very low. Most respondents reported that they were satisfied with their access to information to make an informed decision about HPV vaccination (196/293, 66.9%). and this was very strongly associated with provision of consent. Despite their young age, the vaccine-eligible girls were often involved in the discussion and decision-making. Most consenting parents were satisfied with the campaign and their decision to vaccinate, with almost 90% indicating they would consent to future HPV vaccination. However, negative media reports about the vaccine campaign created confusion and concern. Local health staff were cited as a trusted source of information to guide decision-making. Just over half of the participants who withheld consent cited vaccine safety fears as the primary reason (23/44, 52.3%). CONCLUSION: This is the first reported experience of HPV introduction in a Pacific Island nation. In a challenging environment with limited community knowledge of HPV and cervical cancer, media controversy and a short lead-time for community education, Fiji has implemented an HPV vaccine campaign that was largely acceptable to the community and achieved a high level of participation. Community sensitisation and education is critical and should include a focus on the local health workforce and the vaccine target group. PMID- 26684659 TI - In times of war, adolescents do not fall silent: Teacher-student social network communication in wartime. AB - Exposure to war is associated with psychological disturbances, but ongoing communication between adolescents and teachers may contribute to adolescents' resilience. This study examined the extent and nature of teacher-student communication on Social Network Sites (SNS) during the 2014 Israel-Gaza war. Israeli adolescents (N = 208, 13-18 yrs) completed information about SNS communication. A subset of these (N = 145) completed questionnaires on social rejection and distress sharing on SNS. More than a half (56%) of the respondents communicated with teachers via SNS. The main content category was 'emotional support'. Adolescents' perceived benefits from SNS communication with teachers were associated with distress sharing. Social rejection was negatively associated with emotional support and perceived benefits from SNS communication. We conclude that SNS communication between teachers and students may provide students with easy access to human connections and emotional support, which is likely to contribute to adolescents' resilience in times of war. PMID- 26684660 TI - Girls feeling good at school: School gender environment, internalization and awareness of socio-cultural attitudes associations with self-esteem in adolescent girls. AB - As society continues to advocate an unrealistically thin body shape, awareness and internalization of appearance and its consequent impact upon self-esteem has become increasingly of concern, particularly in adolescent girls. School gender environment may influence these factors, but remains largely unexplored. This study aimed to assess differences between two different school environments in appearance attitudes, social influences and associations with self-esteem. Two hundred and twelve girls (M = 13.8 years) attending either a single-sex or co educational school completed measures on socio-cultural attitudes towards appearance, social support and self-esteem. Though marginal differences between school environments were found, significantly higher internalization was reported among girls at the co-educational school. School environment moderated relations between internalization and self-esteem such that girls in co-educational environments had poorer self-esteem stemming from greater internalization. Thus, in a single-sex school environment, protective factors may attenuate negative associations between socio-cultural attitudes towards appearance and self-esteem in adolescent girls. PMID- 26684661 TI - Comparison of Growth Plate Violations for Transtibial and Anteromedial Surgical Techniques in Simulated Adolescent Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Increases in the rates and intensity of youth sports participation have led to an elevated incidence of anterior cruciate ligament (ACL) injuries and reconstruction in adolescents. Traditional reconstruction techniques in the skeletally immature patient may violate the growth plates and potentially lead to deformities. HYPOTHESIS/PURPOSE: The purpose of this study was to compare the volume and location of femoral growth plate violations resulting from anteromedial (AM) and transtibial (TT) techniques in ACL reconstruction. The hypothesis was that the more oblique angle used in femoral tunnels drilled with the AM portal technique would produce larger and more lateral violations compared with those resulting from TT tunnels. STUDY DESIGN: Controlled laboratory study. METHODS: Growth plate disturbances were quantified by performing simulated reconstructions in computer models created from magnetic resonance imaging scans of the knees of 17 adolescent participants. Locations of tunnels drilled with simulated AM and TT portal techniques were specified by an orthopaedic surgeon blinded to the locations of the femoral physes in the knee models. Tunnels with lengths of 20, 25, and 30 mm were placed in each model using simulated drill diameters of 7, 8, and 9 mm in addition to a 4.5-mm tunnel breaching the lateral cortex. Normalized measures of the volume and laterality of violations were computed. RESULTS: Tunnels drilled with the AM portal technique disrupted a significantly larger percentage of the physis (P = .007), but the difference was not substantial. Tunnels drilled with the AM portal technique produced violations that were more lateral in the physis than those drilled with the TT technique (P < .001). Tunnels drilled with the AM portal technique resulted in mean violations that were 5.1% +/- 2.1% of the physis as compared with 4.7% +/- 2.0% for TT tunnels. The mean value for a normalized measure of the laterality of the violation (L score) was 0.590 +/- 0.115 for tunnels drilled with the AM portal technique and 0.290 +/- 0.104 for TT tunnels. The AM approach produced 16 of 153 simulated reconstructions with growth plate violations greater than 8% compared with only 10 with the TT approach. CONCLUSION: Results suggest that the AM approach produces growth plate violations that are larger and more lateral than the violations generated using the TT technique. AM approaches were more likely to remove more than 8% of the physeal volume, a level previously identified as posing a greater risk of growth disturbances. While the difference in the mean physeal volume removed between the approaches was small, the violations for the AM approach were much more lateral, a finding of potentially greater clinical significance. CLINICAL RELEVANCE: As progressively younger patients are considered candidates for ACL reconstruction, knowledge of how variations in technique affect the developing knee is critical to preventing iatrogenic injuries. PMID- 26684662 TI - Greater Mechanical Loading During Walking Is Associated With Less Collagen Turnover in Individuals With Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Individuals who have sustained an anterior cruciate ligament (ACL) injury and undergo ACL reconstruction (ACLR) are at higher risk of developing knee osteoarthritis. It is hypothesized that altered knee loading may influence the underlying joint metabolism and hasten development of posttraumatic knee osteoarthritis. PURPOSE: To explore the associations between serum biomarkers of cartilage metabolism and peak vertical ground-reaction force (vGRF) and vGRF loading rate in the injured and uninjured limbs of individuals with ACLR. STUDY DESIGN: Descriptive laboratory study. METHODS: Patients with a history of a primary unilateral ACLR who had returned to unrestricted physical activity (N = 19) participated in the study. Resting blood was collected from each participant before completing 5 walking gait trials at a self-selected comfortable speed. Peak vGRF was extracted for both limbs during the first 50% of the stance phase of gait, and the linear vGRF loading rate was determined between heel strike and peak vGRF. Sera were assessed for collagen breakdown (collagen type II cleavage product [C2C]) and synthesis (collagen type II C-propeptide [CPII]), as well as aggrecan concentrations, via commercially available specific enzyme-linked immunosorbent assays. Pearson product-moment correlations (r) and Spearman rank order correlations (rho) were used to evaluate associations between loading characteristics and biomarkers of cartilage metabolism. RESULTS: Lower C2C:CPII ratios were associated with higher peak vGRF in the injured limb (rho = -0.59, uncorrected P = .007). There were no significant associations between peak vGRF or linear vGRF loading rate and CPII, C2C, or aggrecan serum concentrations. CONCLUSION: Lower C2C:CPII ratios were associated with higher peak vGRF in the ACLR limb during gait, suggesting that higher peak loading in the ACLR limb is related to lower type II collagen breakdown relative to type II collagen synthesis. CLINICAL RELEVANCE: These data suggest that type II collagen synthesis may be higher relative to the amount of type II collagen breakdown in the ACLR limb with higher lower extremity loading. Future study should determine if metabolic compensations to increase collagen synthesis may affect the risk of developing osteoarthritis after ACLR. PMID- 26684664 TI - Pain Management After Outpatient Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials. AB - BACKGROUND: Effective pain management after anterior cruciate ligament (ACL) reconstruction improves patient satisfaction and function. PURPOSE: To collect and evaluate the available evidence from randomized controlled trials (RCTs) on pain control after ACL reconstruction. STUDY DESIGN: Systematic review. METHODS: A systematic literature review was performed using PubMed, Medline, Google Scholar, UpToDate, Cochrane Reviews, CINAHL, and Scopus following PRISMA guidelines (July 2014). Only RCTs comparing a method of postoperative pain control to another method or placebo were included. RESULTS: A total of 77 RCTs met inclusion criteria: 14 on regional nerve blocks, 21 on intra-articular injections, 4 on intramuscular/intravenous injections, 12 on multimodal regimens, 6 on oral medications, 10 on cryotherapy/compression, 6 on mobilization, and 5 on intraoperative techniques. Single-injection femoral nerve blocks provided superior analgesia to placebo for up to 24 hours postoperatively; however, this also resulted in a quadriceps motor deficit. Indwelling femoral catheters utilized for 2 days postoperatively provided superior analgesia to a single injection femoral nerve block. Local anesthetic injections at the surgical wound site or intra-articularly provided equivalent analgesia to regional nerve blocks. Continuous-infusion catheters of a local anesthetic provided adequate pain relief but have been shown to cause chondrolysis. Cryotherapy improved analgesia compared to no cryotherapy in 4 trials, while in 4 trials, ice water and water at room temperature provided equivalent analgesic effects. Early weightbearing decreased pain compared to delayed weightbearing. Oral gabapentin given preoperatively and oral zolpidem given for the first week postoperatively each decreased opioid consumption as compared to placebo. Ibuprofen reduced pain compared to acetaminophen. Oral ketorolac reduced pain compared to hydrocodone acetaminophen. CONCLUSION: Regional nerve blocks and intra-articular injections are both effective forms of analgesia. Cryotherapy-compression appears to be beneficial, provided that intra-articular temperatures are sufficiently decreased. Early mobilization reduces pain symptoms. Gabapentin, zolpidem, ketorolac, and ibuprofen decrease opioid consumption. Despite the vast amount of high-quality evidence on this topic, further research is needed to determine the optimal multimodal approach that can maximize recovery while minimizing pain and opioid consumption. CLINICAL RELEVANCE: These results provide the best available evidence from RCTs on pain control regimens after ACL reconstruction. PMID- 26684663 TI - An In Vitro Robotic Assessment of the Anterolateral Ligament, Part 1: Secondary Role of the Anterolateral Ligament in the Setting of an Anterior Cruciate Ligament Injury. AB - BACKGROUND: Recent investigations have described the structural and functional behavior of the anterolateral ligament (ALL) of the knee through pull-apart and isolated sectioning studies. However, the secondary stabilizing role of the ALL in the setting of a complete anterior cruciate ligament (ACL) tear has not been fully defined for common simulated clinical examinations, such as the pivot shift, anterior drawer, and internal rotation tests. HYPOTHESIS: Combined sectioning of the ALL and ACL would lead to increased internal rotation and increased axial plane translation during a pivot-shift test when compared with isolated sectioning of the ACL. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen human cadaveric knees were subjected to a simulated pivot-shift test with coupled 10-N.m valgus and 5-N.m internal rotation torques from 0 degrees to 60 degrees of knee flexion and a 5-N.m internal rotation torque and an 88-N anterior tibial load, both from 0 degrees to 120 degrees of knee flexion via a 6 degrees of freedom robotic system. Kinematic changes were measured and compared with the intact state for isolated sectioning of the ACL and combined sectioning of the ACL and ALL. RESULTS: Combined sectioning of the ACL and ALL resulted in a significant increase in axial plane tibial translation during a simulated pivot shift at 0 degrees , 15 degrees , 30 degrees , and 60 degrees of knee flexion and a significant increase in internal rotation at 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , 90 degrees , 105 degrees , and 120 degrees when compared with the intact and ACL deficient states. Based on the model results, ALL sectioning resulted in an additional 2.1 mm (95% CI, 1.4-2.9 mm; P < .001) of axial plane translation during the pivot shift when compared with ACL-only sectioning, when pooling evidence over all flexion angles. Likewise, when subjected to IR torque, the ACL+ALL-deficient state resulted in an additional 3.2 degrees of internal rotation (95% CI, 2.4 degrees -4.1 degrees ; P < .001) versus the intact state, and the additional sectioning of the ALL increased internal rotation by 2.7 degrees (95% CI, 1.8 degrees -3.6 degrees ; P < .001) versus the ACL-deficient state. CONCLUSION: The results of this study confirm the ALL as an important lateral knee structure that provides rotatory stability to the knee. Specifically, the ALL was a significant secondary stabilizer throughout flexion during an applied internal rotation torque and simulated pivot-shift test in the context of an ACL-deficient knee. CLINICAL RELEVANCE: Residual internal rotation and a positive pivot shift after ACL reconstruction may be attributed to ALL injury. For these patients, surgical treatment of an ALL tear may be considered. PMID- 26684665 TI - Prospects of Colloidal Copper Chalcogenide Nanocrystals. AB - Over the past few years, colloidal copper chalcogenide nanocrystals (NCs) have emerged as promising alternatives to conventional Cd and Pb chalcogenide NCs. Owing to their wide size, shape, and composition tunability, Cu chalcogenide NCs hold great promise for several applications, such as photovoltaics, lighting and displays, and biomedical imaging. They also offer characteristics that are unparalleled by Cd and Pb chalcogenide NCs, such as plasmonic properties. Moreover, colloidal Cu chalcogenide NCs have low toxicity, potentially lower costs, and excellent colloidal stability. This makes them attractive materials for the large-scale deployment of inexpensive, sustainable, and environmentally benign solution-processed devices. Nevertheless, the synthesis of colloidal Cu chalcogenide NCs, especially that of ternary and quaternary compositions, has yet to reach the same level of mastery as that available for the prototypical Cd chalcogenide based NCs. This review provides a concise overview of this rapidly advancing field, sketching the state of the art and highlighting the key challenges. We discuss recent developments in the synthesis of size-, shape-, and composition-controlled NCs of Cu chalcogenides, with emphasis in strategies to circumvent the limitations arising from the need to precisely balance the reactivities of multiple precursors in synthesizing ternary and quaternary compositions. In this respect, we show that topotactic cation-exchange reactions are a promising alternative route to complex multinary Cu chalcogenide NCs and hetero-NCs, which are not attainable by conventional routes. The properties and potential applications of Cu chalcogenide NCs and hetero-NCs are also addressed. PMID- 26684666 TI - Erratum to: Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. PMID- 26684667 TI - A novel pre-treatment for the methane production from microalgae by using N methylmorpholine-N-oxide (NMMO). AB - The aim of this work was to study the effect of the solvent N-methylmorpholine-N oxide (NMMO) to pre-treat Nannochloropsis oculata before the anaerobic digestion process. The results indicated that the pre-treatment affects the characteristics of the cell wall, which consequently becomes more susceptible to the microorganisms attack during anaerobic digestion. The methane production was increased by 43% after the pre-treatment, from 238+/-6mLCH4/gVS until 339+/ 4mLCH4/gVS. On the contrary, the methane production from Chlorella vulgaris decreased after the pre-treatment from 251+/-4mLCH4/gVS to 231+/-3mLCH4/gVS. The failure on the pre-treatment was attributed to the particular characteristics of the substrate in consequence of a previous drying step. PMID- 26684668 TI - 127 Steps Toward a More Active World. PMID- 26684669 TI - Monitoring Global Progress of Physical Activity: The Role and Progress of Civil Society in Holding Governments to Account. PMID- 26684670 TI - The shorter the better? A follow-up analysis of 10-session psychiatric treatment including the motive-oriented therapeutic relationship for borderline personality disorder. AB - OBJECTIVE: There is little research on short-term treatments for borderline personality disorder (BPD). While the core changes may occur only in long-term treatments, short-term treatments may enable the study of early generic processes of engagement in therapy and thus inform about effective treatment components. It was shown that a 10-session version of a psychiatric treatment was effective in reducing borderline symptoms at the end of this treatment [Kramer, U., Kolly, S., Berthoud, L., Keller, S., Preisig, M., Caspar, F., ... Despland, J.-N. (2014). Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment for borderline personality disorder: A randomized controlled trial. Psychotherapy and Psychosomatics, 83, 176-186.]. Also, it was demonstrated in a randomized design that adding the motive-oriented therapeutic relationship (MOTR), following an individualized case formulation based on Plan Analysis, further increased general outcome after session 10 and had a positive effect on the early changes in self-esteem and alliance. METHOD: The present study focuses on the follow-up period after this initial treatment, examining treatment density and outcomes after 6 months and service utilization after 12 months. Outcome was measured using the OQ-45. RESULTS: Results on a sub-sample of N = 40 patients with available OQ-45 data at follow-up (n = 21 for MOTR treatment, n = 19 for comparison treatment) showed maintenance of gains over the follow-up period, which did not differ between both conditions. It appeared for this sample that MOTR treatments, while using the same number of sessions, lasted more weeks (i.e., lower treatment density, defined as the number of sessions per week), when compared to the treatments without MOTR. Density marginally predicted symptom reduction at follow-up. Patients in MOTR treatments had a greater likelihood of entering structured psychotherapy after the initial sessions than patients in the comparison group. CONCLUSIONS: These results are overall consistent with earlier studies on short-term treatments for BPD and underline the importance of individualizing interventions, by using case formulations that rely on idiographic methods and integrative concepts. PMID- 26684672 TI - Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer's disease related cognitive functioning. AB - There is an urgent need to develop molecular biomarkers of brain age in order to advance our understanding of age related neurodegeneration. Recently, we developed a highly accurate epigenetic biomarker of tissue age (known as epigenetic clock) which is based on DNA methylation levels. Here we use n=700 dorsolateral prefrontal cortex (DLPFC) samples from Caucasian subjects of the Religious Order Study and the Rush Memory and Aging Project to examine the association between epigenetic age and Alzheimer's disease (AD) related cognitive decline, and AD related neuropathological markers. Epigenetic age acceleration of DLPFC is correlated with several neuropathological measurements including diffuse plaques (r=0.12, p=0.0015), neuritic plaques (r=0.11, p=0.0036), and amyloid load (r=0.091, p=0.016). Further, it is associated with a decline in global cognitive functioning (beta=-0.500, p=0.009), episodic memory (beta=-0.411, p=0.009) and working memory (beta=-0.405, p=0.011) among individuals with AD. The neuropathological markers may mediate the association between epigenetic age and cognitive decline. Genetic complex trait analysis (GCTA) revealed that epigenetic age acceleration is heritable (h2=0.41) and has significant genetic correlations with diffuse plaques (r=0.24, p=0.010) and possibly working memory (r=-0.35, p=0.065). Overall, these results suggest that the epigenetic clock may lend itself as a molecular biomarker of brain age. PMID- 26684673 TI - Phytoremediation potential of some halophytic species for soil salinity. AB - Phytoremediation potential of six halophytic species i.e. Suaeda nudiflora, Suaeda fruticosa, Portulaca oleracea, Atriplex lentiformis, Parkinsonia aculeata and Xanthium strumarium was assessed under screen house conditions. Plants were raised at 8.0, 12.0, 16.0, and 20.0 dSm(-1) of chloride-dominated salinity. The control plants were irrigated with canal water. Sampling was done at vegetative stage (60-75 DAS). About 95 percent seed germination occurred up to 12 dSm(-1) and thereafter declined slightly. Mean plant height and dry weight plant(-1) were significantly decreased from 48.71 to 32.44 cm and from 1.73 to 0.61g plant(-1) respectively upon salinization. Na(+)/K(+) ratio (0.87 to 2.72), Na(+)/ Ca(2+) + Mg(2+) (0.48 to 1.54) and Cl(-)/SO4(2-) (0.94 to 5.04) ratio showed increasing trend. Salinity susceptibility index was found minimum in Suaeda fruticosa (0.72) and maximum in Parkinsonia aculeata (1.17). Total ionic content also declined and magnitude of decline varied from 8.51 to 18.91% at 8 dSm(-1) and 1.85 to 7.12% at 20 dSm(-1) of salinity. On the basis of phytoremediation potential Suaeda fruticosa (1170.02 mg plant(-1)), Atriplex lentiformis (777.87 mg plant(-1)) were the best salt hyperaccumulator plants whereas Xanthium strumarium (349.61 mg plant(-1)) and Parkinsonia aculeata (310.59 mg plant(-1)) were the least hyperaccumulator plants. PMID- 26684675 TI - Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors. AB - Malaria symptoms and pathogenesis are caused by blood stage parasite burdens of Plasmodium spp., for which invasion of red blood cells (RBCs) by merozoites is essential. Successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding RBC invasion. To understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activity in vitro. Accordingly, methods have been developed to isolate invasive Plasmodium knowlesi and Plasmodium falciparum merozoites. Rodent malaria parasite models offer ease in laboratory maintenance and experimental genetic modifications; however, no methods have been reported regarding isolation of high numbers of invasive rodent malaria merozoites. In this study, Plasmodium yoelii-infected RBCs were obtained from infected mice, and mature schizont infected RBCs enriched via HistodenzTM density gradients. Merozoites retaining invasion activity were then isolated by passing the preparations through a filter membrane. RBC-invaded parasites developed to mature stages in vitro in a synchronous manner. Isolated merozoites were evaluated for retention of invasion activity following storage at different temperatures prior to incubation with uninfected mouse RBCs. Isolated merozoites retained their invasion activity 4h after isolation at 10 or 15 degrees C, whereas their invasion activity reduced to 0-10% within 30 min when incubated on ice or at 37 degrees C prior to RBC invasion assay. Images of merozoites at successive steps during RBC invasion were captured by light and transmission electron microscopy. Synthetic peptides derived from the amino acid sequence of the P. yoelii invasion protein RON2 efficiently inhibited RBC invasion. The developed method to isolate and keep invasive P. yoelii merozoites for up to 4h is a powerful tool to study the RBC invasion biology of this parasite. This method provides an important platform to evaluate the mode of action of drugs and vaccine candidates targeting the RBC invasion steps using rodent malaria model. PMID- 26684676 TI - Naked-eye quantitative aptamer-based assay on paper device. AB - This work initially describes the design of low-cost, naked-eye quantitative aptamer-based assays by using microfluidic paper-based analytical device (MUPAD). Two new detection motifs are proposed for quantitative MUPAD measurement without using external electronic readers, which depend on the length of colored region in a strip-like MUPAD and the number of colorless detection microzones in a multi zone MUPAD. The length measuring method is based on selective color change of paper from colorless to blue-black via formation of iodine-starch complex. The counting method is conducted on the basis of oxidation-reduction reaction between hydrogen peroxide and potassium permanganate. Their utility is well demonstrated with sensitive, specific detection of adenosine as a model analyte with the naked eye in buffer samples and undiluted human serum. These equipment-free quantitative methods proposed thus hold great potential for the development of more aptamer-based assays that are simple, cost-efficient, portable, and user friendly for various point-of-care applications particularly in resource constrained environments. PMID- 26684678 TI - A Strain-Insensitive Stretchable Electronic Conductor: PEDOT:PSS/Acrylamide Organogels. AB - Organogel-based stretchable electronic conductors exhibit electrical conduction even under a large stretching deformation of 300% without electrochemical reactions at DC voltages. The resistance change with stretching is almost strain insensitive up to 50% strain and it remains at each deformation up to 1000 fatigue cycle. The polymeric conductive paths of PEDOT: PSS are well preserved during the mechanical deformation. PMID- 26684677 TI - [Pancreatic neuroendocrine tumours. What do we know of their history?]. AB - Starting with Paul Langerhans, who first described pancreatic islets in 1869, this article reviews the various protagonists who, in the last century and a half, have contributed to the discovery of the main hormones originating in the pancreas, the analytical methods for their measurement, the imaging techniques for identifying tumoural location, and the various pancreatic neoplasms. PMID- 26684679 TI - Developing networks between residential aged care facilities as a result of engagement in a falls prevention project: an action research study. AB - BACKGROUND: Residential aged care facility (RACF) staff often operate in isolation. Research is lacking on networking between facilities. AIMS: To explore outcomes associated with network formation between two RACFs as part of an action research approach to reducing falls. DESIGN: Action research approach with qualitative data collected. METHODS: Twelve RACF staff from two facilities in regional Tasmania, Australia, formed a falls prevention action research group. Thematic analysis was undertaken of 22 audio-recorded fortnightly group meetings. RESULTS: This was the first opportunity for participants to meet colleagues from another facility in a professional context. The formation of an inter-facility network enabled the sharing of ideas and systems related to evidence-based falls prevention activities and other issues and galvanised a collaborative focus for action. CONCLUSIONS: An action research process can be used to create an inter facility network. Such networks can decrease staff isolation and facilitate best resident care. PMID- 26684680 TI - Balancing Ethical Uncertainty: The Dance of Interprofessional Roles. AB - Interprofessional (IP) education has emerged globally as a means of improving overall healthcare quality, and to increase healthcare provider understanding of other roles. However, in situations of moral uncertainly, there are not clear procedures to address IP role interactions when tension and conflict emerge. This study reports secondary analysis findings from data in a large study related to moral distress in IP ethics consultations and collaborations. A basic qualitative, exploratory approach was utilized for data analysis with overtones of grounded theory. Eleven IP participants representing five disciplines comprised the sample. A model of IP role interaction was constructed from themes which were revealed to identify distinct facilitating actions and barriers as components of IP interactions serving to balance ethical decision making in the context of patient care. Specific role boundaries of the professions identified uncertainty as they interacted with multiple healthcare roles in patient care dilemmas. PMID- 26684674 TI - Leukocyte arrest: Biomechanics and molecular mechanisms of beta2 integrin activation. AB - Integrins are a group of heterodimeric transmembrane receptors that play essential roles in cell-cell and cell-matrix interaction. Integrins are important in many physiological processes and diseases. Integrins acquire affinity to their ligand by undergoing molecular conformational changes called activation. Here we review the molecular biomechanics during conformational changes of integrins, integrin functions in leukocyte biorheology (adhesive functions during rolling and arrest) and molecules involved in integrin activation. PMID- 26684681 TI - National Initiatives to Improve Healthcare Outcomes: A Comparative Study of Health Delivery Systems in Slovakia and the United States. AB - While the United States and Slovakia offer different healthcare delivery systems, each country faces the same challenges of improving the health status of their populations. The authors explore the impact of their respective systems on the health of their populations and compare the health outcomes of both nations. They point out that socioeconomic factors play a far more important role in determining population health outcomes than do the structures of the systems surrounding the care delivery. The authors illustrate this finding through a comparison of the poverty and education levels of a selected minority group from each country in relation to the health outcomes for each population group. The comparison reveals that education is a more influential determinant in a population's health outcomes, than the improved access to care offered by a universal system. PMID- 26684682 TI - Understanding Obesity Perceptions in America: An Exploratory Study of Public Perceptions of the Problem and Possible Actions for Health Product Marketers. AB - Many healthcare professionals have stated that obesity is a major problem in the United States. The rate of obesity in young people has been rising until just recently, when it was reported to have leveled off. The authors examine the problem in terms of people's perception of how great a problem it is, along with examining their perception of the causes and possible remedies for the problem. If the general population does not believe that a problem exists, then corrective action will be hampered. Then, the authors examine what impact this has on marketing products to address this problem. PMID- 26684684 TI - The Tulip GT(r) airway versus the facemask and Guedel airway: a randomised, controlled, cross-over study by Basic Life Support-trained airway providers in anaesthetised patients. AB - We performed a randomised, controlled, cross-over study of lung ventilation by Basic Life Support-trained providers using either the Tulip GT(r) airway or a facemask with a Guedel airway in 60 anaesthetised patients. Successful ventilation was achieved if the provider produced an end-tidal CO2 > 3.5 kPa and a tidal volume > 250 ml in two of the first three breaths, within 60 sec and within two attempts. Fifty-seven (95%) providers achieved successful ventilation using the Tulip GT compared with 35 (58%) using the facemask (p < 0.0001). Comparing the Tulip GT and facemask, the mean (SD) end-tidal CO2 was 5.0 (0.7) kPa vs 2.5 (1.5) kPa, tidal volume was 494 (175) ml vs 286 (186) ml and peak inspiratory pressure was 18.3 (3.4) cmH2 O vs 13.6 (7) cmH2 O respectively (all p < 0.0001). Forty-seven (78%) users favoured the Tulip GT airway. These results are similar to a previous manikin study using the same protocol, suggesting a close correlation between human and manikin studies for this airway device. We conclude that the Tulip GT should be considered as an adjunct to airway management both within and outside hospitals when ventilation is being undertaken by Basic Life Support-trained airway providers. PMID- 26684685 TI - Median Sternotomy or Right Thoracotomy Techniques for Total Artificial Heart Implantation in Calves. AB - The choice of optimal operative access technique for mechanical circulatory support device implantation ensures successful postoperative outcomes. In this study, we retrospectively evaluated the median sternotomy and lateral thoracotomy incisions for placement of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) in a bovine model. The CFTAH was implanted in 17 calves (Jersey calves; weight range, 77.0-93.9 kg) through a median sternotomy (n = 9) or right thoracotomy (n = 8) for elective chronic implantation periods of 14, 30, or 90 days. Similar preoperative preparation, surgical techniques, and postoperative care were employed. Implantation of the CFTAH was successfully performed in all cases. Both methods provided excellent surgical field visualization. After device connection, however, the median sternotomy approach provided better visualization of the anastomoses and surgical lines for hemostasis confirmation and repair due to easier device displacement, which is severely limited following right thoracotomy. All four animals sacrificed after completion of the planned durations (up to 90 days) were operated through full median sternotomy. Our data demonstrate that both approaches provide excellent initial field visualization. Full median sternotomy provides larger viewing angles at the anastomotic suture line after device connection to inflow and outflow ports. PMID- 26684686 TI - An elastic band exercise programme improves functional fitness in older adults. PMID- 26684687 TI - Emergency department nurses report high workload and management pressure to meet 4 h treatment targets. PMID- 26684688 TI - Conceptual clarification for Grand Challenges. PMID- 26684689 TI - Interdisciplinarity, grand challenges, and the future of knowledge. PMID- 26684690 TI - Women Who Have Sex with Women in Kenya and Their Sexual and Reproductive Health. AB - PURPOSE: To describe sexual and reproductive health characteristics of women who have sex with women (WSW) in Kenya's three most populous cities: Kisumu, Mombasa, and Nairobi. Although the last decade has shown an upsurge of health-related research studies in African sexual minority populations, these studies have generally concentrated on the health status of men who have sex with men to the exclusion of WSW. This study presents the first findings on Kenyan WSW's sexual and reproductive health. METHODS: A community-based, cross-sectional survey was conducted among 280 women who were at least 18 years old, had at least one female sexual partner in the past three years, and were Kenyan residents. RESULTS: A significant proportion of participants reported that they had at least one male sexual partner in the past three years (38.9%), ever had an abortion (13.2%), been infected with at least one sexually transmitted infection (STI) in the past three years (33.9%), and been tested for HIV at least once (88.9%). Of the women who reported having been tested for HIV, 9.4% (7.5% of the total sample) received a positive test result. Some women noted that they were open with their doctors about their sexual orientation, and that their doctors had not reacted negatively to this information. CONCLUSION: WSW in Kenya are at risk for negative sexual and reproductive health outcomes, including HIV, STIs, unplanned pregnancy, and unsafe abortion, positioning these women as a critical population for public health efforts. Some WSW actively exercise their agency in making important health decisions. Therefore, this study indicates a need to incorporate WSW's health concerns within Kenyan national health policy programming. PMID- 26684691 TI - Recent Progress on Graphene-based Electrochemical Biosensors. AB - The detailed records and conclusions on the important advancements in graphene based electrochemical biosensors have been reviewed. Due to their outstanding properties, graphene-based materials have been widely studied for the accurate electrochemical detection of many biomolecules, which is extremely vital to the development of biomedical instruments, clinical diagnosis, and disease treatment. This review discusses the graphene research for the effective immobilization of enzymes, including glucose oxidase, horseradish peroxidase, and hemoglobin, etc., and the accurate detection of biomolecules, including glucose, hydrogen peroxide, dopamine, ascorbic acid, uric acid, nicotinamide adenine dinucleotide, DNA, RNA, and carcinoembryonic antigen, etc. In most of the cases, the graphene-based biosensors exhibited remarkable performance with high sensitivities, wide linear detection ranges, low detection limits, and long-term stabilities. PMID- 26684692 TI - Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation. AB - Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61.5%) and 187 (38.5%) cases, respectively. Of note, seven of the 111 (6.3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV 6B reactivation and chronic/recurrent benign lymphadenopathy. PMID- 26684694 TI - Profiling for primary-care presentation, investigation and referral for liver cancers: evidence from a national audit. AB - BACKGROUND AND AIM: The incidence of liver cancer across Europe is increasing. There is a lack of evidence within the current literature on the identification and investigation of liver cancer within primary care. We aimed to profile liver cancer recognition and assessment as well as the timeliness of liver cancer diagnosis from within the primary-care setting in the UK. METHODS: Data were obtained from the National Audit of Cancer Diagnosis in Primary Care 2009-2010 and analysed. We calculated the patient interval, the primary-care interval and the number of prereferral consultations for liver cancer. We then compared these data with prior data on the respective indicators for other common cancers. RESULTS: The median patient interval was 9 days (interquartile range 0-31 days), and the median primary-care interval for liver cancer was 11 days (interquartile range 0-40 days). Of the 90 patients, 21 (23.3%) had three or more consultations with their general practitioner before specialist referral. For the three metrics (patient interval, primary-care interval and number of prereferral consultations), liver cancer has average or longer intervals when compared with other cancers. The most common symptomatic presentation of liver cancer within the primary-care setting was right upper quadrant pain (11%), followed by decompensated liver failure (9%). Of the patients, 12% were diagnosed with liver cancer on the basis of an incidental finding of an abnormal liver function test. CONCLUSION: This study provides a detailed and thorough overview of the recognition of liver cancer and the promptness of liver cancer identification in an English context, and should inform strategies for improving the timeliness of diagnosis. PMID- 26684693 TI - Identifying patients at higher risk of hepatocellular carcinoma recurrence after liver transplantation in a multicenter cohort study from Argentina. AB - BACKGROUND AND AIM: The Up-to-7 criteria on the basis of the explanted liver features categorize patients at higher risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). The aim of this study was to propose a novel pretransplant scoring system to predict recurrence including pre-LT data. PATIENTS AND METHODS: From 763 consecutive adult patients who underwent transplantation in four LT centers from Argentina, 124 patients with HCC were included. A scoring system was developed in 87 patients from pre-LT risk factors for recurrence as determined by hazard ratios (HRs) from a multivariate Cox regression analysis. RESULTS: Overall survival and recurrence rates at 5 years were 63.3 and 13.7%, respectively, during a follow-up period of 3.5+/-2.2 years. Variables associated with HCC recurrence on multivariate analysis were alpha fetoprotein more than 100 ng/ml (HR=5.6, P=0.001) and tumor beyond Up-to-7 imaging criteria (HR=6.3, P=0.001). Bootstrap validation showed that overfitting was negligible. Scoring points were assigned as follows (0-2 points): pre-LT alpha-fetoprotein more than 100 ng/ml (presence=1 point, absence=0 point), and tumor beyond Up-to-7 imaging criteria (presence=1 point, absence=0 point). AUROC curve indicated a c-statistic of 0.74 (0.58-0.88, P=0.003). Two distinct subgroups of patients were identified with a cut-off more than or equal to 1 point (62% sensitivity and 82% specificity): low risk (0 point) and high risk (1 2 points). The 5-year recurrence rate was 9.4 and 44.5% (P=0.0001) and the 5-year overall survival was 78.1 and 34.8% (P=0.0001) in the low-risk and high-risk groups, respectively. CONCLUSION: This scoring model may be a useful additional tool for HCC recurrence risk stratification before LT. Prospective studies are needed to evaluate our model. PMID- 26684696 TI - Specific IgE to recombinant protein (Ber e 1) for the diagnosis of Brazil nut allergy. PMID- 26684695 TI - Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth. AB - The ribosome has historically been considered to have no cell-specific function but rather serve in a "housekeeping" capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ~fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth. J. Cell. Physiol. 231: 1894-1902, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26684698 TI - Acral peeling skin syndrome associated with a novel CSTA gene mutation. AB - Acral peeling skin syndrome (APSS) is a rare autosomal recessive condition, characterized by asymptomatic peeling of the skin of the hands and feet, often linked to mutations in the gene TGM5. However, more recently recessive loss of function mutations in CSTA, encoding cystatin A, have been linked with APSS and exfoliative ichthyosis. We describe the clinical features in two sisters with APSS, associated with a novel large homozygous deletion encompassing exon 1 of CSTA. PMID- 26684699 TI - Unifying and diversifying workplace-based efforts for promoting health and preventing disability. PMID- 26684700 TI - Nature contact and organizational support during office working hours: Benefits relating to stress reduction, subjective health complaints, and sick leave. AB - BACKGROUND: Improving social support, and providing nature contact at work are potential health promoting workplace interventions. OBJECTIVE: The objective was to investigate whether nature contact at work is associated with employee's health and participation, and to study whether the possible associations between nature contact and health can be explained by perceived organizational support. METHOD: Data were collected through a web-based, cross-sectional survey of employees in seven public and private office workplaces in Norway (n = 707, 40% response rate). Multiple linear and logistic regression analysis were performed on 565 participants fulfilling inclusion criteria. RESULTS: A greater amount of indoor nature contact at work was significantly associated with less job stress (B = -0.18, CI = -0.318 to -0.042), fewer subjective health complaints (B = 0.278, CI = -0.445 to -0.112) and less sickness absence (B = -0.061, CI = -0.009 to -0.002). Perceived organizational support mediated the associations between indoor nature contact and job stress and sickness absence, and partly mediated the association with subjective health complaints. Outdoor nature contact showed no reliable association with the outcomes in this study. CONCLUSIONS: Extending nature contact in the physical work environment in offices, can add to the variety of possible health-promoting workplace interventions, primarily since it influences the social climate on the workplace. PMID- 26684701 TI - Content and key components of vocational rehabilitation on care farms for unemployed people with mental health problems: A case study report. AB - BACKGROUND: Mental health problems are a major cause for new disability grants in Norway. A variety of approaches in vocational rehabilitation is needed for this group. Green work is one such program that has been implemented at Norwegian care farms, which aims to promote health and support the transition from unemployment to working life. OBJECTIVE: To describe care farms in Norway and identify the presence of key components of such vocational programs. METHODS: In this case study, we used The Norwegian National Register of Care Farms to gain an overview of farms with vocational rehabilitation programs. Data consisted of written information from five farms' own web-site together with answers from a cross sectional questionnaire. Content about programs was systematically extracted by using national green work guidelines. RESULTS: Descriptions of care farm programs showed that key components outlined by the national guidelines for green work were present. These components were; (1) variety of work activities, (2) adaptation of work tasks, (3) the farmers' support and supervision, (4) experiencing nature, (5) enhanced structure in everyday life. CONCLUSION: The description of vocational programs on care farms in relation to these key components, gives a thorough understanding of the content and organization of such programs. PMID- 26684702 TI - Mental health rehabilitation in a care farm context: A descriptive review of Norwegian intervention studies. AB - BACKGROUND: C are farming is a service developed at farms for promoting mental and physical health and is increasingly used in mental health rehabilitation in Norway. OBJECTIVE: This article aims to present a descriptive review of Norwegian intervention research on care farms that provide rehabilitation for people with mental health disorders. METHODS: This literature review applied a non-systematic search strategy: all articles in the field known to the authors were selected for inclusion. The selected studies were intervention studies that were conducted on farms in Norway, that used adult participants with mental health problems/disorders, and that reported outcome measures related to mental health. The studies and articles presented quantitative and/or qualitative data. RESULTS: The findings from the published articles report improvements to mental health problems, such as depression, anxiety, perceived stress, positive affect, rumination, and self-efficacy. Qualitative data describe a variety of positive experiences, such as improved coping ability, increased social support, and appreciation of the care farm activity. CONCLUSION: Participating in interventions on care farms positively influences mental health. Care farming may therefore be used as a supplementary approach in mental health rehabilitation, as it offers meaningful and engaging occupations and social inclusion. PMID- 26684703 TI - Patients' recovery experiences of indoor plants and viewsof nature in a rehabilitation center. AB - BACKGROUND: There is an increasing interest in the possible healing factors connected to the presence of nature elements in health institutions. OBJECTIVE: The aim of the present study is to get a deeper understanding of how residents in a residential rehabilitation center experience the views through windows and the indoor plants, and whether and how the view and the plants can impact their recovery process. METHODS: In-depth individual and group interviews were conducted among 16 residents at a rehabilitation center in Norway. RESULTS: The participants said that the indoor plants and the view of nature were pleasant to look at and elicited feelings of relaxation and positive emotions which contributed to opportunities for reflection and contemplation. They expressed a feeling of connectedness to nature: a feeling of wholeness and spirituality elicited by the nature elements. They also expressed that the presence of nature elements contributed to a sense of being taken care of. CONCLUSIONS: The nature elements, such as a view of nature or indoor plants, seem to enhance opportunities for reflection, feelings of meaningfulness and sense of being taken care of which may strengthen their feeling of well-being and make them more resilient to the stressors in life. PMID- 26684704 TI - Making the healthier choice at work the easier choice: From a focus on risk factors to health promotion. PMID- 26684705 TI - Do psychological job demands, decision control and social support predictreturn to work three months after a return-to-work (RTW) programme? The rapid-RTW cohort study. AB - BACKGROUND: Long-term sickness absence is a considerable health and economic problem in the industrialised world. Factors that might predict return to work (RTW) are therefore of interest. OBJECTIVE: To examine the impact of psychosocial work characteristics on RTW three months after the end of a RTW programme. METHODS: A cohort study of 251 sick-listed employees from 40 different treatment and rehabilitation services in Norway recruited from February to December 2012. The Job Content Questionnaire was used to gather information on the psychosocial work conditions. Full or partial RTW was measured three months after the end of the RTW programme, using data from the national sickness absence register. Logistic regression analyses were performed to investigate the association between the psychosocial work characteristics and RTW. RESULTS: Having low psychological job demands (OR = 0.4, 95% CI: 0.2-0.9), high co-worker- (OR = 3.4, 95% CI: 1.5-5.8), and supervisor support (OR = 3.4, 95% CI: 1.6-7.3), and being in a low-strain job (low job demands and high control) (OR = 4.6, 95% CI: 1.1 18.6) were predictive of being in work three months after the end of the RTW programme, after adjusting for several potential prognostic factors. CONCLUSION: Interventions aimed at returning people to work might benefit from putting more emphasise on psychosocial work characteristics in the future. PMID- 26684706 TI - Autonomy support and need satisfaction in prevocational programs on care farms: The self-determination theory perspective. AB - BACKGROUND: Mental health problems are leading causes for early and prolonged withdrawal from the workforce. Green work on care farms represents a prevocational training program intended to stimulate return to work for people with mental health problems. Research suggests that care farms may improve mental health, but there is still little knowledge of the subjective perspective of clients in green work programs. OBJECTIVE: To gain a deeper and broader understanding of the individual experiences of people with mental health problems participating in green work on care farms in Norway. METHODS: A hermeneutic phenomenological research design was applied. Ten semi-structured interviews were conducted. The self-determination theory (SDT) was adapted to gain a deeper understanding of the themes that emerged in the analysis process of the interviews. RESULTS: Five main themes materialize describing participants' experiences within the green work program. The main themes consist of (1) structure and flexibility, (2) understanding and acknowledgement, (3) guidance and positive feedback, (4) nature and animals, and (5) reflections on personal functioning and the future. CONCLUSION: The main themes identified indicate a high degree of autonomy support and need satisfaction within the care farm context, which according to SDT can facilitate good human functioning, and well being. PMID- 26684707 TI - Maximizing work integration in job placement of individuals facing mental health problems: Supervisor experiences. AB - BACKGROUND: Many people confronting mental health problems are excluded from participation in paid work. Supervisor engagement is essential for successful job placement. OBJECTIVE: To elicit supervisor perspectives on the challenges involved in fostering integration to support individuals with mental health problems (trainees) in their job placement at ordinary companies. METHODS: Explorative, qualitative designed study with a phenomenological approach, based on semi-structured interviews with 15 supervisors involved in job placements for a total of 105 trainees (mean 7, min-max. 1-30, SD 8). Data were analysed using qualitative content analysis. RESULTS: Superviors experience two interrelated dilemmas concerning knowledge of the trainee and degree of preferential treatment. Challenges to obtaining successful integration were; motivational: 1) Supervisors previous experience with trainees encourages future engagement, 2) Developing a realistic picture of the situation, and 3) Disclosure and knowledge of mental health problems, and continuity challenges: 4) Sustaining trainee cooperation throughout the placement process, 5) Building and maintaining a good relationship between supervisor and trainee, and 6) Ensuring continuous cooperation with the social security system and other stakeholders. CONCLUSIONS: Supervisors experience relational dilemmas regarding pre-judgment, privacy and equality. Job placement seem to be maximized when the stakeholders are motivated and recognize that cooperation must be a continuous process. PMID- 26684708 TI - Green exercise as a workplace intervention to reduce job stress. Results from a pilot study. AB - BACKGROUND: Stress and mental fatigue are major health threats to employees in office-based occupations. Physical activity is widely used as a stress-management intervention for employees. Moreover, experiences in contact with nature have been shown to provide stress-reduction and restoration from mental fatigue. OBJECTIVES: In a pilot study designed as a randomized controlled trial we investigated the impact of a green-exercise intervention on psychological and physiological indicators of stress in municipality employees. METHODS: Fourteen employees (7 females and 7 males, 49+/-8 yrs) volunteered in an exercise-based intervention in workplace either outdoors in a green/nature area or in an indoor exercise-setting. The intervention consisted of an information meeting and two exercise sessions, each including a biking bout and a circuit-strength sequence using elastic rubber bands (45-minutes, at about 55% of HR reserve, overall). Main outcomes were perceived environmental potential for restoration, affective state, blood pressure (BP) and cortisol awakening response (CAR AUC(G) and CAR AUC(I)) and cortisol levels in serum. Measurements were taken at baseline and in concomitance with the exercise sessions. Furthermore, affective state and self reported physical activity levels were measured over a 10-weeks follow-up period. RESULTS: Compared with the indoor group, the nature group reported higher environmental potential for restoration (p < 0.001) and Positive Affect (p < 0.01), along with improved CAR AUC(I) (p = 0.04) and, marginally, diastolic BP (p = 0.05). The nature group also reported higher ratings of Positive Affect at follow-up (p = 0.02). Differences at post-exercise were not found for any of the other components of affective state, systolic BP, CAR AUC(G) and cortisol levels measured in serum. CONCLUSIONS: Green-exercise at the workplace could be a profitable way to manage stress and induce restoration among employees. Further studies on larger samples are needed in order to improve the generalizability of the results. PMID- 26684710 TI - From a feeling of uselessness to renewed belief in self and a future. PMID- 26684709 TI - Motivations, experiences and challenges of being a care farmer -results of a survey of Norwegian care farmers. AB - BACKGROUND: Care farming is an increasing part of multifunctional agriculture. Still there are few studies on how the farmers experience their working situation. OBJECTIVE: To describe care farmers' relevant education, motivation, perceived support, involvement with participants, and perceived strain. We also wanted to investigate the possible relationship between different variables and level of perceived strain. METHODS: A total of 98 (67%) Norwegian care farmers answered a postal questionnaire in 2011 on demography, motivation, relevant education, involvement in participants, and 11 statements describing perceived strain of care farming. A sum-score of the 11 statements was constructed, and a linear regression model was used to explore the relationships between total perceived strain and the other variables. RESULTS: Of the farmers 40% had relevant education. Their main motivation was economical (53%) or "idealistic" (47%). 80% reported that care farming had increased their quality of life. Still the majority experienced it to be socially demanding, and 26% did not receive support from professionals. Higher total perceived strain was found for men, low education, no perceived support, high degree of involvement, and less perceived functionality of participants. The model explained 40% of the variance in total perceived strain. CONCLUSION: More systematic cooperation and supervision from the social and health care system might be needed, in order to ensure a health promoting work situation for these care farmers. PMID- 26684711 TI - Dihydroartemisinin, an Anti-Malaria Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis, Osteoclast Formation, and RANKL-Induced Signaling Pathways. AB - Osteoporosis is an osteolytic disease that features enhanced osteoclast formation and bone resorption. Identification of agents that can inhibit osteoclast formation and function is important for the treatment of osteoporosis. Dihydroartemisinin is a natural compound used to treat malaria but its role in osteoporosis is not known. Here, we found that dihydroartemisinin can suppress RANKL-induced osteoclastogenesis and bone resorption in a dose-dependent manner. Dihydroartemisinin inhibited the expression of osteoclast marker genes such as cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAcP). Furthermore, dihydroartemisinin inhibited RANKL-induced NF-kappaB and NFAT activity. In addition, using an in vivo ovariectomized mouse model, we show that dihydroartemisinin is able to reverse the bone loss caused by ovariectomy. Together, this study shows that dihydroartemisinin attenuates bone loss in ovariectomized mice through inhibiting RANKL-induced osteoclast formation and function. This indicates that dihydroartemisinin, the first physiology or medicine nobel prize discovery of China, is a potential treatment option against osteolytic bone disease. (c) 2015 American Society for Bone and Mineral Research. PMID- 26684712 TI - Molecular Epidemiology of Mycobacterium bovis in Humans and Cattle. AB - Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), is a serious re-emerging disease in both animals and humans. The evolution of the Multi- and Extensively drug-resistant M. bovis strains (MDR-TB and XDR-TB) represents a global threat to public health. Worldwide, the disease is responsible for great economic losses in the veterinary field, serious threat to the ecosystem, and about 3.1% of human TB cases, up to 16% in Tanzania. Only thorough investigation to understand the pathogen's epidemiology can help in controlling the disease and minimizing its threat. For this purpose, various tools have been developed for use in advanced molecular epidemiological studies of bTB, either alone or in combination with standard conventional epidemiological approaches. These techniques enable the analysis of the intra- and inter-species transmission dynamics of bTB. The delivered data can reveal detailed insights into the source of infection, correlations among human and bovine isolates, strain diversity and evolution, spread, geographical localization, host preference, tracing of certain virulence factors such as antibiotic resistance genes, and finally the risk factors for the maintenance and spread of M. bovis. They also allow for the determination of epidemic and endemic strains. This, in turn, has a significant diagnostic impact and helps in vaccine development for bTB eradication programs. The present review discusses many topics including the aetiology, epidemiology and importance of M. bovis, the prevalence of bTB in humans and animals in various countries, the molecular epidemiology of M. bovis, and finally applied molecular epidemiological techniques. PMID- 26684713 TI - Comment on the study 'Cerebrospinal fluid lactate: measurement of an adult reference interval' by Sally D Slack, Paul Turley, Victoria Allgar and Ian B Holbrook. PMID- 26684714 TI - Assessment Following Distal Radius Fractures: A Comparison of 4 Scoring Systems, Visual Numerical Scales, and Objective Measurements. AB - PURPOSE: To compare 4 recognized upper-limb scoring systems that are regularly used to assess wrist function after injury. METHODS: We reviewed 116 patients 6 months after volar locking plate fixation for distal radius fractures. Two purely subjective and 2 composite scoring systems composed of both subjective and objective components were compared along with visual numerical scores for pain and function and objective measures of function. Each score was standardized into a scale from 0 to 100. RESULTS: The distribution of the standardized total scores was statistically significantly different and indicated marked variability between scoring systems and therefore the information provided. Overall, the subjective scoring systems correlated well with each other and with both visual numerical scores for pain and function. However, the composite scores and objective measures of function correlated poorly with the subjective scores including the visual numerical scores. CONCLUSIONS: Results from wrist scoring systems should be interpreted with caution. It is important to ensure that the component parts of each score are taken into consideration separately because total scores may be misleading. CLINICAL RELEVANCE: Composite scores may be outdated and should be avoided. PMID- 26684715 TI - Use of the Volar Plate of the Distal Interphalangeal Joint as a Distally Based Flap in Flexor Tendon Surgery. AB - The usual treatment for flexor digitorum profundus (FDP) avulsions as well as FDP lacerations in the distal part of zone I is tendon reinsertion into bone. Although there are several different techniques of FDP tendon reinsertion into bone, they are generally complex and have a weak tensile strength. A technique for treating these injuries is to use the volar plate of the distal interphalangeal joint as a distally based flap for tendon repair. The current communication discusses the technique and its potential complications. Initial clinical experience is encouraging and the volar plate flap technique may take its place in flexor tendon surgery. PMID- 26684716 TI - An investigation of exciton behavior in type-II self-assembled GaSb/GaAs quantum dots. AB - We report the investigation of exciton dynamics in type-II self-assembled GaSb/GaAs quantum dots. The GaSb/GaAs quantum dots (QDs) were grown using a modified liquid phase epitaxy technique. Statistical size distributions of the uncapped QDs were investigated experimentally by field-emission scanning electron microscopy (SEM) and atomic force microscopy (AFM), and theoretically by an eight band k . p calculation, which demonstrated a dissolution effect. Furthermore, the low-temperature luminescence spectra of type-II GaSb/GaAs QDs with a thick capping layer exhibit well-resolved emission bands and LO-phonon-assisted transitions in the GaSb wetting layer. However, the luminescence lines quench at temperatures above 250 K, which is attributed to the weak quantum confinement of electrons participating in indirect exciton recombination. It was demonstrated that the room temperature stability of the excitons in type-II GaSb/GaAs QDs could be achieved by growing thin a capping layer, which provides strong quantum confinement in the conduction band and enhances the electron-hole Coulomb interaction, stabilizing the excitons. PMID- 26684718 TI - Pseudo VA Linking With Atrial Overdrive Pacing: Importance of Pacing Site. PMID- 26684717 TI - Bioorthogonal Fluorophore Linked DFO-Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies. AB - Herein we describe the development and application of a bioorthogonal fluorogenic chelate linker that can be used for facile creation of labeled imaging agents. The chelate linker is based on the trans-cyclooctene(TCO)-tetrazine(Tz) chemistry platform and incorporates deferoxamine (DFO) as a (89)Zr PET tracer and a BODIPY fluorophore for multimodal imaging. The rapid (<3 min) ligation between mAb-TCO and Tz-BODIPY-DFO chelator is monitored using fluorescence and allows for determination of labeling completion. Utilizing BODIPY as the linker between mAb and DFO facilitates in chelator quantification using spectrophotometry, allowing for an alternative to traditional methods (mass and isotope dilution assay). Radiolabeling with (89)Zr to form (89)Zr-DFO-BODIPY-trastuzumab was found to be quantitative after incubation at room temperature for 1 h (1.5 mCi/mg specific activity). The cell binding assay using HER2+ (BT474) and HER2- (BT20) cell lines showed significant binding to (89)Zr-DFO-BODIPY-trastuzumab (6.45 +/- 1.87% in BT474 versus 1.47 +/- 0.39% in BT20). In vivo PET imaging of mice bearing BT20 or BT474 xenografts with (89)Zr-DFO-BODIPY-trastuzumab showed high tumor conspicuity, and biodistribution confirmed excellent, specific probe uptake of 237.3 +/- 14.5% ID/g in BT474 xenografts compared to low, nonspecific probe uptake in BT20 xenografts (16.4 +/- 5.6% ID/g) 96 h p.i. . Ex vivo fluorescence (465ex/520em) of selected tissues confirmed superb target localization and persistence of the fluorescence of (89)Zr-DFO-BODIPY-trastuzumab. The described platform is universally adaptable for simple antibody labeling. PMID- 26684719 TI - Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing. AB - Wound healing is a complicated process, and fibroblast is a major cell type that participates in the process. Recent studies have shown that bioglass (BG) can stimulate fibroblasts to secrete a multitude of growth factors that are critical for wound healing. Therefore, we hypothesize that BG can stimulate fibroblasts to have a higher bioactivity by secreting more bioactive growth factors and proteins as compared to untreated fibroblasts, and we aim to construct a bioactive skin tissue engineering graft for wound healing by using BG activated fibroblast sheet. Thus, the effects of BG on fibroblast behaviors were studied, and the bioactive skin tissue engineering grafts containing BG activated fibroblasts were applied to repair the full skin lesions on nude mouse. Results showed that BG stimulated fibroblasts to express some critical growth factors and important proteins including vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, collagen I, and fibronectin. In vivo results revealed that fibroblasts in the bioactive skin tissue engineering grafts migrated into wound bed, and the migration ability of fibroblasts was stimulated by BG. In addition, the bioactive BG activated fibroblast skin tissue engineering grafts could largely increase the blood vessel formation, enhance the production of collagen I, and stimulate the differentiation of fibroblasts into myofibroblasts in the wound site, which would finally accelerate wound healing. This study demonstrates that the BG activated skin tissue engineering grafts contain more critical growth factors and extracellular matrix proteins that are beneficial for wound healing as compared to untreated fibroblast cell sheets. PMID- 26684720 TI - Simultaneous determination of ledipasvir, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study. AB - In this work, a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ledipasvir, sofosbuvir and its metabolite GS-331007 in rat plasma was developed. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm*50mm, 1.7MUm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 889.8->130.1 for ledipasvir, m/z 530.3->243.1 for sofosbuvir, m/z 261.5->113.1 for GS-331007 and m/z 285.2->193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 2-500ng/mL for ledipasvir, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatography was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<10.2% and the accuracy values ranged from -9.8% to 11.2%. The method was successfully applied to a pharmacokinetic study of ledipasvir, sofosbuvir and GS 331007 in rats. PMID- 26684721 TI - Life-history strategies and carbon metabolism gene dosage in the Nakaseomyces yeasts. AB - The Nakaseomyces clade consists of a group of six hemiascomyceteous yeasts (Candida glabrata, Nakaseomyces delphensis, C. nivarensis, C. bracarensis, C. castelli, N. bacillisporus), phylogenetically close to the yeast Saccharomyces cerevisiae, their representative being the well-known pathogenic yeast C. glabrata. Four species had been previously examined for their carbon assimilation properties and found to have similar properties to S. cerevisiae (repression of respiration in high glucose-i.e. Crabtree positivity-and being a facultative anaerobe). We examined here the complete set of the six species for their carbon metabolic gene content. We also measured different metabolic and life-history traits (glucose consumption rate, population growth rate, carrying capacity, cell size, cell and biomass yield). We observed deviations from the glycolytic gene redundancy observed in S. cerevisiae presumed to be an important property for the Crabtree positivity, especially for the two species C. castelli and N. bacillisporus which frequently have only one gene copy, but different life strategies. Therefore, we show that the decrease in carbon metabolic gene copy cannot be simply associated with a reduction of glucose consumption rate and can be counterbalanced by other beneficial genetic variations. PMID- 26684723 TI - CORRIGENDUM. PMID- 26684722 TI - The birth of a deadly yeast: tracing the evolutionary emergence of virulence traits in Candida glabrata. AB - The yeast Candida glabrata is an opportunistic human fungal pathogen whose incidence has increased in the last two decades. Despite its name, this yeast is only distantly related to the model fungal pathogen C. albicans, and more closely related to Saccharomyces cerevisiae and other yeasts that underwent an ancient whole-genome duplication. Understanding what specific traits make C. glabrata a successful opportunistic pathogen within a clade of mostly innocuous yeasts, and how these compare to virulence traits in distant pathogens such as C. albicans is a focus of intense research. From an evolutionary perspective, uncovering how the ability to infect humans has emerged multiple, independent times in different lineages may reveal new disease mechanisms and provide us with the capacity to predict which genomic features in a clade may confer a higher potential to develop virulence against humans. PMID- 26684724 TI - Viral-load point-of-care technologies to achieve an AIDS-free generation. PMID- 26684725 TI - Progressive reduction versus fixed level of support during training: When less is less. AB - Previous empirical and theoretical work suggests that effective skill acquisition requires movements to be generated actively and that learning new skills supports the acquisition of prospective control. However, there are many ways in which practice can be structured, that may affect the acquisition and use of prospective control after training. Here, we tested whether the progressive modulation and reduction of support during training was required to yield good performance after training without support. The task was to use a stylus to push a bead over a complex 3D wire path. The support "magnetically" attracted and held the stylus onto the wire. Three groups of adult participants each experienced one of three training regimes: gradual reduction of magnetic attraction, only a medium level of attraction, or low magnetic attraction. The results showed that use of a single (medium) level of support was significantly less effective in yielding good performance with low support after training. Training with low support yielded post-training performance that was equally good as that yielded by training with progressive reduction of support; however, performance during training was significantly poorer in the former. Thus, less support during training yields effective learning but more difficult training sessions. The results are discussed in the context of application to training with special populations. PMID- 26684726 TI - Trunk coordination in healthy and chronic nonspecific low back pain subjects during repetitive flexion-extension tasks: Effects of movement asymmetry, velocity and load. AB - Multiple joint interactions are critical to produce stable coordinated movements and can be influenced by low back pain and task conditions. Inter-segmental coordination pattern and variability were assessed in subjects with and without chronic nonspecific low back pain (CNSLBP). Kinematic data were collected from 22 CNSLBP and 22 healthy volunteers during repeated trunk flexion-extension in various conditions of symmetry, velocity, and loading; each at two levels. Sagittal plane angular data were time normalized and used to calculate continuous relative phase for each data point. Mean absolute relative phase (MARP) and deviation phase (DP) were derived to quantify lumbar-pelvis and pelvis-thigh coordination patterns and variability. Statistical analysis revealed more in phase coordination pattern in CNSLBP (p=0.005). There was less adaptation in the DP for the CNSLBP group, as shown by interactions of Group by Load (p=.008) and Group by Symmetry by Velocity (p=.03) for the DP of pelvis-thigh and lumbar pelvis couplings, respectively. Asymmetric (p<0.001) and loaded (p=0.04) conditions caused less in-phase coordination. Coordination variability was higher during asymmetric and low velocity conditions (p<0.001). In conclusion, coordination pattern and variability could be influenced by trunk flexion extension conditions. CNSLBP subjects demonstrated less adaptability of movement pattern to the demands of the flexion-extension task. PMID- 26684727 TI - Efficacy of Myrtus communis L. to Inactivate the Hydatid Cyst Protoscoleces. AB - PURPOSE: The present study aims to investigate the scolicidal effects of Myrtus communis L. essential oil against protoscoleces of hydatid cysts and also its toxicity in mice model. MATERIALS AND METHODS: Protoscoleces were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the essential oil (12.5-100 MUl/ml) were used for 5-30 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1% eosin staining). Moreover, 48 male NMRI mice were used to determine the acute and sub-acute toxicity of M. communis essential oil. One-way ANOVA with Tukey's post-hoc test was used to assess differences between experimental groups. RESULTS: Findings of the present study demonstrated that the M. communis essential oil at the concentration of 100 MUl/ml after 5 min of exposure killed 100% protoscoleces. Similarly, the mean mortality rate of protoscoleces after 10 min of exposure to concentration of 50 MUl/ml was 100%. However, lower concentrations (12.5 and 25 MUl/ml) of M. communis essential oil provoked a delayed protoscolicidal effects. The LD50 values of intraperitoneal injection of the M. communis essential oil was 2.23 mL/kg body wt. No significant difference (p > .05) was observed in the clinical chemistry and hematological parameters following oral administrations of M. communis essential oil at the doses 0.05, 0.1, 0.2, and 0.4 mL/kg for 14 days. CONCLUSION: The results showed potent scolicidal activity of M. communis with no significant toxicity, which might be used as a natural scolicidal agent in hydatid cyst surgery. PMID- 26684728 TI - Relative importance of evolutionary dynamics depends on the composition of microbial predator-prey community. AB - Community dynamics are often studied in subsets of pairwise interactions. Scaling pairwise interactions back to the community level is, however, problematic because one given interaction might not reflect ecological and evolutionary outcomes of other functionally similar species interactions or capture the emergent eco-evolutionary dynamics arising only in more complex communities. Here we studied this experimentally by exposing Pseudomonas fluorescens SBW25 prey bacterium to four different protist predators (Tetrahymena pyriformis, Tetrahymena vorax, Chilomonas paramecium and Acanthamoeba polyphaga) in all possible single-predator, two-predator and four-predator communities for hundreds of prey generations covering both ecological and evolutionary timescales. We found that only T. pyriformis selected for prey defence in single-predator communities. Although T. pyriformis selection was constrained in the presence of the intraguild predator, T. vorax, T. pyriformis selection led to evolution of specialised prey defence strategies in the presence of C. paramecium or A. polyphaga. At the ecological level, adapted prey populations were phenotypically more diverse, less stable and less productive compared with non-adapted prey populations. These results suggest that predator community composition affects the relative importance of ecological and evolutionary processes and can crucially determine when rapid evolution has the potential to change ecological properties of microbial communities. PMID- 26684729 TI - Evolution of metabolic divergence in Pseudomonas aeruginosa during long-term infection facilitates a proto-cooperative interspecies interaction. AB - The effect of polymicrobial interactions on pathogen physiology and how it can act either to limit pathogen colonization or to potentiate pathogen expansion and virulence are not well understood. Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found together in polymicrobial human infections. However, we have previously shown that the interactions between these two bacterial species are strain dependent. Whereas P. aeruginosa PAO1, a commonly used laboratory strain, effectively suppressed S. aureus growth, we observed a commensal-like interaction between the human host-adapted strain, DK2 P2M24-2003, and S. aureus. In this study, characterization by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry (IMS) and mass spectral (MS) molecular networking revealed a significant metabolic divergence between P. aeruginosa PAO1 and DK2-P2M24-2003, which comprised several virulence factors and signaling 4-hydroxy-2-alkylquinoline (HAQ) molecules. Strikingly, a further modulation of the HAQ profile was observed in DK2-P2M24-2003 during interaction with S. aureus, resulting in an area with thickened colony morphology at the P. aeruginosa-S. aureus interface. In addition, we found an HAQ-mediated protection of S. aureus by DK2-P2M24-2003 from the killing effect of tobramycin. Our findings suggest a model where the metabolic divergence manifested in human host-adapted P. aeruginosa is further modulated during interaction with S. aureus and facilitate a proto-cooperative P. aeruginosa-S. aureus relationship. PMID- 26684730 TI - The symbiotic life of Symbiodinium in the open ocean within a new species of calcifying ciliate (Tiarina sp.). AB - Symbiotic partnerships between heterotrophic hosts and intracellular microalgae are common in tropical and subtropical oligotrophic waters of benthic and pelagic marine habitats. The iconic example is the photosynthetic dinoflagellate genus Symbiodinium that establishes mutualistic symbioses with a wide diversity of benthic hosts, sustaining highly biodiverse reef ecosystems worldwide. Paradoxically, although various species of photosynthetic dinoflagellates are prevalent eukaryotic symbionts in pelagic waters, Symbiodinium has not yet been reported in symbiosis within oceanic plankton, despite its high propensity for the symbiotic lifestyle. Here we report a new pelagic photosymbiosis between a calcifying ciliate host and the microalga Symbiodinium in surface ocean waters. Confocal and scanning electron microscopy, together with an 18S rDNA-based phylogeny, showed that the host is a new ciliate species closely related to Tiarina fusus (Colepidae). Phylogenetic analyses of the endosymbionts based on the 28S rDNA gene revealed multiple novel closely related Symbiodinium clade A genotypes. A haplotype network using the high-resolution internal transcribed spacer-2 marker showed that these genotypes form eight divergent, biogeographically structured, subclade types that do not seem to associate with any benthic hosts. Ecological analyses using the Tara Oceans metabarcoding data set (V9 region of the 18S rDNA) and contextual oceanographic parameters showed a global distribution of the symbiotic partnership in nutrient-poor surface waters. The discovery of the symbiotic life of Symbiodinium in the open ocean provides new insights into the ecology and evolution of this pivotal microalga and raises new hypotheses about coastal pelagic connectivity. PMID- 26684731 TI - An evidence-based framework for predicting the impact of differing autotroph heterotroph thermal sensitivities on consumer-prey dynamics. AB - Increased temperature accelerates vital rates, influencing microbial population and wider ecosystem dynamics, for example, the predicted increases in cyanobacterial blooms associated with global warming. However, heterotrophic and mixotrophic protists, which are dominant grazers of microalgae, may be more thermally sensitive than autotrophs, and thus prey could be suppressed as temperature rises. Theoretical and meta-analyses have begun to address this issue, but an appropriate framework linking experimental data with theory is lacking. Using ecophysiological data to develop a novel model structure, we provide the first validation of this thermal sensitivity hypothesis: increased temperature improves the consumer's ability to control the autotrophic prey. Specifically, the model accounts for temperature effects on auto- and mixotrophs and ingestion, growth and mortality rates, using an ecologically and economically important system (cyanobacteria grazed by a mixotrophic flagellate). Once established, we show the model to be a good predictor of temperature impacts on consumer-prey dynamics by comparing simulations with microcosm observations. Then, through simulations, we indicate our conclusions remain valid, even with large changes in bottom-up factors (prey growth and carrying capacity). In conclusion, we show that rising temperature could, counterintuitively, reduce the propensity for microalgal blooms to occur and, critically, provide a novel model framework for needed, continued assessment. PMID- 26684732 TI - Letter re: A systematic approach to subgroup analysis in a smoking cessation trial. PMID- 26684733 TI - Discrimination of tenants with a visual impairment on the housing market: Empirical evidence from correspondence tests. AB - BACKGROUND: According to the social model of disability, physical 'impairments' become disabilities through exclusion in social relations. An obvious form of social exclusion might be discrimination, for instance on the rental housing market. Although discrimination has detrimental health effects, very few studies have examined discrimination of people with a visual impairment. OBJECTIVES: We aim to study (1) the extent of discrimination of individuals with a visual impairment on the rental housing market and (2) differences in rates of discrimination between landowners and real estate agents. METHODS: We conducted correspondence tests among 268 properties on the Belgian rental housing market. Using matched tests, we compared reactions by realtors and landowners to tenants with and tenants without a visual impairment. RESULTS: The results show that individuals with a visual impairment are substantially discriminated against in the rental housing market: at least one in three lessors discriminate against individuals with a visual impairment. We further discern differences in the propensity toward discrimination according to the type of lessor. Private landlords are at least twice as likely to discriminate against tenants with a visual impairment than real estate agents. At the same time, realtors still discriminate against one in five tenants with a visual impairment. CONCLUSIONS: This study shows the substantial discrimination against visually people with an impairment. Given the important consequences discrimination might have for physical and mental health, further research into this topic is needed. PMID- 26684734 TI - Urinary iodine and stable isotope analysis to examine habitat influences on thyroid hormones among coastal dwelling American alligators. AB - The American alligator, generally a freshwater species, is known to forage in marine environments despite the lack of a salt secreting gland found in other crocodylids. Estuarine and marine foraging could lead to increased dietary uptake of iodine, a nutrient necessary for the production of thyroid hormones. To explore the influence of dietary iodine on thyroid hormone health of coastal dwelling alligators, we described the seasonal plasma thyroxine and triiodothyronine concentrations measured by radioimmunoassay and urinary iodine (UI) concentrations measured by inductively coupled plasma mass spectrometry. We also analyzed long-term dietary patterns through stable isotope analysis of scute tissue. Snout-to-vent length (SVL) was a significant factor among UI and stable isotope analyses. Large adult males greater than 135cm SVL had the highest UI concentrations but did not display seasonality of thyroid hormones. Alligators under 135 SVL exhibited seasonality in thyroid hormones and a positive relationship between UI and triiodothyronine concentrations. Isotopic signatures provided supporting evidence that large males predominantly feed on marine/estuarine prey whereas females showed reliance on freshwater/terrestrial prey supplemented by marine/estuarine prey. UI measurement provided immediate information that correlated to thyroid hormone concentrations whereas stable isotope analysis described long-term dietary patterns. Both techniques demonstrate that adult alligators in coastal environments are utilizing estuarine/marine habitats, which could alter thyroid hormone physiology. PMID- 26684736 TI - [Erratum to: Congenital hip dysplasia, screening and therapy]. PMID- 26684735 TI - Dudrick Research Symposium 2015-Lean Tissue and Protein in Health and Disease. AB - The 2015 Dudrick Research Symposium "Lean Tissue and Protein in Health and Disease: Key Targets and Assessment Strategies" was held on February 16, 2015, at Clinical Nutrition Week in Long Beach, California. The Dudrick Symposium honors the many pivotal and innovative contributions to the development and advancement of parenteral nutrition made by Dr Stanley J. Dudrick, physician scientist, academic leader, and a founding member of the American Society for Parenteral and Enteral Nutrition. As the 2014 recipient of the Dudrick award, Dr Carrie Earthman chaired the symposium and was the first of 3 speakers, followed by Dr Robert Wolfe and Dr Steven Heymsfield. The symposium addressed the importance of lean tissue to health and response to disease and injury, as well as the many opportunities and challenges in its assessment at the bedside. Lean tissue assessment is beneficial to clinical care in chronic and acute care clinical settings, given the strong relationship between lean tissue and outcomes, including functional status. Currently available bioimpedance techniques, including the use of bioimpedance parameters, for lean tissue and nutrition status assessment were presented. The connection between protein requirements and lean tissue was discussed, highlighting the maintenance of lean tissue as one of the most important primary end points by which protein requirements can be estimated. The various tracer techniques to establish protein requirements were presented, emphasizing the importance of practical considerations in research protocols aimed to establish protein requirements. Ultrasound and other new and emerging technologies that may be used for lean tissue assessment were discussed, and areas for future research were highlighted. PMID- 26684737 TI - A Functional Tricarboxylic Acid Cycle Operates during Growth of Bordetella pertussis on Amino Acid Mixtures as Sole Carbon Substrates. AB - It has been claimed that citrate synthase, aconitase and isocitrate dehydrogenase activities are non-functional in Bordetella pertussis and that this might explain why this bacterium's growth is sometimes associated with accumulation of polyhydroxybutyrate (PHB) and/or free fatty acids. However, the sequenced genome includes the entire citric acid pathway genes. Furthermore, these genes were expressed and the corresponding enzyme activities detected at high levels for the pathway when grown on a defined medium imitating the amino acid content of complex media often used for growth of this pathogenic microorganism. In addition, no significant PHB or fatty acids could be detected. Analysis of the carbon balance and stoichiometric flux analysis based on specific rates of amino acid consumption, and estimated biomass requirements coherent with the observed growth rate, clearly indicate that a fully functional tricarboxylic acid cycle operates in contrast to previous reports. PMID- 26684738 TI - Knowledge, Beliefs and Practices of Patients with Diabetic Retinopathy at the University Hospital of the West Indies, Jamaica. AB - To determine the knowledge, beliefs and practices of patients with diabetic retinopathy attending the Retina Eye Clinic at the University Hospital of the West Indies. A prospective study was done using a questionnaire with a sample population of 150 patients. The questions included their knowledge about the frequency of their eye examination, the relevance of exercise and a healthy diet, the role of the ophthalmologist and their views on the importance of compliance with medications for diabetes and hypertension. One hundred and fifty patients were recruited. Sixty six percent (99/150) were females and 34 % (51/150) males. The ages ranged from 29 to 83 years (mean +/- SD, 56.1 +/- 10.3) years. Type II diabetes was more common; 63 and 79 % of females and males respectively. A minority (19.8 %) obtained tertiary education. The mean % knowledge scores were 86 +/- 14 for males and 82.8 +/- 16.4 for females (p = 0.260). Prior to attending the retina clinic, 50 % were unaware of the need for annual eye examinations. Compliance with medication, exercise and a special diet was seen in 73, 40.3 and 49.7 % respectively. Current knowledge scores were good. However, knowledge about the timing and frequency of eye examinations prior to attending the retina clinic was inadequate. Correct knowledge and beliefs did not correspond to a high level of compliant practices. PMID- 26684739 TI - Targeted Ovarian Cancer Education for Hispanic Women: A Pilot Program in Arizona. AB - In disadvantaged populations, including Hispanics, there is a deficit in understanding of cancer risk factors, symptoms, prevention, and treatment. The objective of this study was to assess ovarian cancer knowledge in a population of Hispanic women in Arizona, identify deficiencies, and to evaluate the utility of an educational program developed specifically for this community's needs. A de novo questionnaire about ovarian cancer was distributed to Hispanic women enrolled in family literacy programs at Mesa Public Schools. Following this assessment, a video educational program was developed, with emphasis on areas of greatest knowledge deficits, and post-intervention assessment administered. Chi square, Wilcoxon rank sum, and Kruskal-Wallis tests were used for analysis. 167 questionnaires were completed in the pretest group and 102 in the post intervention group. Between groups, there were no differences in age (p = 0.49), education (p = 0.68), or annual income (p = 0.26). In the pretest group, 45 % of questions were answered correctly versus 84 % in the post-test group (p < 0.01). 24.2 % of the initial respondents correctly identified ovarian cancer symptoms versus 85.6 of post-test respondents (p < 0.01). With the program, there was an increase in the number of correct post-test responses for each question and symptom (p < 0.01), except those about hereditary risk of ovarian cancer (p = 0.62) and pelvic anatomy (p = 0.16). Following identification of an ovarian cancer knowledge deficit in this cohort of Hispanic women, an educational tool targeting specific deficiencies successfully increased cancer knowledge and awareness of symptoms. Similar efforts in this and other minority populations should be continued. PMID- 26684740 TI - Arthroscopic partial trapeziectomy and tendon interposition for thumb carpometacarpal arthritis. AB - BACKGROUND: The purpose of this study was to introduce arthroscopic partial trapeziectomy and tendon interposition for the treatment of symptomatic thumb carpometacarpal arthritis of Eaton stage II or III. METHODS: From August 2001 to April 2009, 23 patients with thumb carpometacarpal arthritis were treated using this technique. Pain score, range of motion, and pinch strength were clinically evaluated and compared with the preoperative values after a minimum follow-up duration of 24 months. RESULTS: Significant reduction in pain score and increases in range of motion and pinch strength were found (all p < 0.001) after a 2-year follow-up. The mean +/- SD (median) postoperative pain score was 1.0 +/- 0.7 (1.0) at rest and 1.3 +/- 0.9 (1.0) during daily activities. The postoperative range of motion was 19.1 degrees +/- 4.2 degrees (20 degrees ) for extension and 35.7 degrees +/- 7.1 degrees (35.0 degrees ) for flexion, and the postoperative pinch strength was 86.5 % +/- 19.9 % (90.0 %). No complications were observed in our patient series. CONCLUSIONS: Arthroscopic partial trapeziectomy and soft tissue interposition could be an alternative treatment method for patients with symptomatic thumb carpometacarpal arthritis of Eaton stage II or III. PMID- 26684741 TI - Correction: PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PMID- 26684742 TI - Significantly higher numbers of proB cells in healthy Caucasians compared to Asians: Is there association with incidence of CLL? PMID- 26684743 TI - Heart Rate Assessment Immediately after Birth. AB - BACKGROUND: Heart rate assessment immediately after birth in newborn infants is critical to the correct guidance of resuscitation efforts. There are disagreements as to the best method to measure heart rate. OBJECTIVE: The aim of this study was to assess different methods of heart rate assessment in newborn infants at birth to determine the fastest and most accurate method. METHODS: PubMed, EMBASE and Google Scholar were systematically searched using the following terms: 'infant', 'heart rate', 'monitoring', 'delivery room', 'resuscitation', 'stethoscope', 'auscultation', 'palpation', 'pulse oximetry', 'electrocardiogram', 'Doppler ultrasound', 'photoplethysmography' and 'wearable sensors'. RESULTS: Eighteen studies were identified that described various methods of heart rate assessment in newborn infants immediately after birth. Studies examining auscultation, palpation, pulse oximetry, electrocardiography and Doppler ultrasound as ways to measure heart rate were included. Heart rate measurements by pulse oximetry are superior to auscultation and palpation, but there is contradictory evidence about its accuracy depending on whether the sensor is connected to the infant or the oximeter first. Several studies indicate that electrocardiogram provides a reliable heart rate faster than pulse oximetry. Doppler ultrasound shows potential for clinical use, however future evidence is needed to support this conclusion. CONCLUSION: Heart rate assessment is important and there are many measurement methods. The accuracy of routinely applied methods varies, with palpation and auscultation being the least accurate and electrocardiogram being the most accurate. More research is needed on Doppler ultrasound before its clinical use. PMID- 26684744 TI - Prospective Environmental Risk Assessment for Sediment-Bound Organic Chemicals: A Proposal for Tiered Effect Assessment. AB - A broadly accepted framework for prospective environmental risk assessment (ERA) of sediment-bound organic chemicals is currently lacking. Such a framework requires clear protection goals, evidence-based concepts that link exposure to effects and a transparent tiered-effect assessment. In this paper, we provide a tiered prospective sediment ERA procedure for organic chemicals in sediment, with a focus on the applicable European regulations and the underlying data requirements. Using the ecosystem services concept, we derived specific protection goals for ecosystem service providing units: microorganisms, benthic algae, sediment-rooted macrophytes, benthic invertebrates and benthic vertebrates. Triggers for sediment toxicity testing are discussed.We recommend a tiered approach (Tier 0 through Tier 3). Tier-0 is a cost-effective screening based on chronic water-exposure toxicity data for pelagic species and equilibrium partitioning. Tier-1 is based on spiked sediment laboratory toxicity tests with standard benthic test species and standardised test methods. If comparable chronic toxicity data for both standard and additional benthic test species are available, the Species Sensitivity Distribution (SSD) approach is a more viable Tier-2 option than the geometric mean approach. This paper includes criteria for accepting results of sediment-spiked single species toxicity tests in prospective ERA, and for the application of the SSD approach. We propose micro/mesocosm experiments with spiked sediment, to study colonisation success by benthic organisms, as a Tier-3 option. Ecological effect models can be used to supplement the experimental tiers. A strategy for unifying information from various tiers by experimental work and exposure-and effect modelling is provided. PMID- 26684745 TI - Perfluorooctane Sulfonate Plasma Half-Life Determination and Long-Term Tissue Distribution in Beef Cattle (Bos taurus). AB - Perfluorooctane sulfonate (PFOS) is used in consumer products as a surfactant and is found in industrial and consumer waste, which ends up in wastewater treatment plants (WWTPs). PFOS does not breakdown during WWTP processes and accumulates in the biosolids. Common practices include application of biosolids to pastures and croplands used for feed, and as a result, animals such as beef cattle are exposed to PFOS. To determine plasma and tissue depletion kinetics in cattle, 2 steers and 4 heifers were dosed with PFOS at 0.098 mg/kg body weight and 9.1 mg/kg, respectively. Plasma depletion half-lives for steers and heifers were 120 +/- 4.1 and 106 +/- 23.1 days, respectively. Specific tissue depletion half-lives ranged from 36 to 385 days for intraperitoneal fat, back fat, muscle, liver, bone, and kidney. These data indicate that PFOS in beef cattle has a sufficiently long depletion half-life to permit accumulation in edible tissues. PMID- 26684746 TI - Diffusion of Messages from an Electronic Cigarette Brand to Potential Users through Twitter. AB - OBJECTIVE: This study explores the presence and actions of an electronic cigarette (e-cigarette) brand, Blu, on Twitter to observe how marketing messages are sent and diffused through the retweet (i.e., message forwarding) functionality. Retweet networks enable messages to reach additional Twitter users beyond the sender's local network. We follow messages from their origin through multiple retweets to identify which messages have more reach, and the different users who are exposed. METHODS: We collected three months of publicly available data from Twitter. A combination of techniques in social network analysis and content analysis were applied to determine the various networks of users who are exposed to e-cigarette messages and how the retweet network can affect which messages spread. RESULTS: The Blu retweet network expanded during the study period. Analysis of user profiles combined with network cluster analysis showed that messages of certain topics were only circulated within a community of e cigarette supporters, while other topics spread further, reaching more general Twitter users who may not support or use e-cigarettes. CONCLUSIONS: Retweet networks can serve as proxy filters for marketing messages, as Twitter users decide which messages they will continue to diffuse among their followers. As certain e-cigarette messages extend beyond their point of origin, the audience being exposed expands beyond the e-cigarette community. Potential implications for health education campaigns include utilizing Twitter and targeting important gatekeepers or hubs that would maximize message diffusion. PMID- 26684747 TI - Design and respondent selection of a population-based study on associations between breast cancer screening, lifestyle and quality of life. AB - BACKGROUND: Only few studies have integrated breast cancer screening, lifestyle, and quality of life. Potential bias due to selective non-response may disrupt associations being investigated. We describe the design of a Finnish population based study on associations between breast cancer screening and various indicators for lifestyle and quality of life, and evaluate the level of bias among the respondents from the first study rounds over 2 years. METHODS: The study target population of 10,000, 49-year-old women was randomly drawn from the Finnish National Population Registry. The data included birth year, marital status, municipality, and primary language. Data on education were retrieved from Statistics Finland. Questionnaires focusing on lifestyle-related risk factors and quality of life were sent to the target population in 2012-13, 1 year before the first invitation to organized breast cancer screening. We evaluated associations between willingness to respond and demographic characteristics in the eligible study population. Additionally, we examined associations between the demographic characteristics and the Satisfaction With Life Scale (SWLS), and evaluated the impact of non-response using inverse probability weighting and multiple imputation. RESULTS: The questionnaire response proportion was 52.4%. Compared to non-respondents, respondents were more often married, academically educated, and native speakers of Finnish or Swedish. Nevertheless, the estimates of the SWLS among the respondents were in line with those corrected by non-response in the eligible study population. CONCLUSIONS: Based on the SWLS, the respondents are representative of women in the entire eligible study population. PMID- 26684748 TI - Fasting Glucose Levels Correlate with Disease Severity of Guillain-Barre Syndrome. AB - OBJECTIVE: A potential association between diabetes and Guillain-Barre syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS. METHODS: Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG. RESULTS: The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge. CONCLUSIONS: Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS. PMID- 26684750 TI - Instruments to assess and measure personal and environmental radiofrequency electromagnetic field exposures. AB - Radiofrequency-electromagnetic field (RF-EMF) exposure of human populations is increasing due to the widespread use of mobile phones and other telecommunication and broadcasting technologies. There are ongoing concerns about potential short- and long-term public health consequences from RF-EMF exposures. To elucidate the RF-EMF exposure-effect relationships, an objective evaluation of the exposures with robust assessment tools is necessary. This review discusses and compares currently available RF-EMF exposure assessment instruments, which can be used in human epidemiological studies. Quantitative assessment instruments are either mobile phone-based (apps/software-modified and hardware-modified) or exposimeters. Each of these tool has its usefulness and limitations. Our review suggests that assessment of RF-EMF exposures can be improved by using these tools compared to the proxy measures of exposure (e.g. questionnaires and billing records). This in turn, could be used to help increase knowledge about RF-EMF exposure induced health effects in human populations. PMID- 26684751 TI - Different leaf cost-benefit strategies of ferns distributed in contrasting light habitats of sub-tropical forests. AB - BACKGROUND AND AIMS: Ferns are abundant in sub-tropical forests in southern China, with some species being restricted to shaded understorey of natural forests, while others are widespread in disturbed, open habitats. To explain this distribution pattern, we hypothesize that ferns that occur in disturbed forests (FDF) have a different leaf cost-benefit strategy compared with ferns that occur in natural forests (FNF), with a quicker return on carbon investment in disturbed habitats compared with old-growth forests. METHODS: We chose 16 fern species from contrasting light habitats (eight FDF and eight FNF) and studied leaf functional traits, including leaf life span (LLS), specific leaf area (SLA), leaf nitrogen and phosphorus concentrations (N and P), maximum net photosynthetic rates (A), leaf construction cost (CC) and payback time (PBT), to conduct a leaf cost benefit analysis for the two fern groups. KEY RESULTS: The two groups, FDF and FNF, did not differ significantly in SLA, leaf N and P, and CC, but FDF had significantly higher A, greater photosynthetic nitrogen- and phosphorus-use efficiencies (PNUE and PPUE), and shorter PBT and LLS compared with FNF. Further, across the 16 fern species, LLS was significantly correlated with A, PNUE, PPUE and PBT, but not with SLA and CC. CONCLUSIONS: Our results demonstrate that leaf cost-benefit analysis contributes to understanding the distribution pattern of ferns in contrasting light habitats of sub-tropical forests: FDF employing a quick-return strategy can pre-empt resources and rapidly grow in the high resource environment of open habitats; while a slow-return strategy in FNF allows their persistence in the shaded understorey of old-growth forests. PMID- 26684752 TI - Molecular Characterization of Two Lysophospholipid:acyl-CoA Acyltransferases Belonging to the MBOAT Family in Nicotiana benthamiana. AB - In the remodeling pathway for the synthesis of phosphatidylcholine (PC), acyl-CoA dependent lysophosphatidylcholine (lysoPC) acyltransferase (LPCAT) catalyzes the reacylation of lysoPC. A number of genes encoding LPCATs have been cloned and characterized from several plants in recent years. Using Arabidopsis and other plant LPCAT sequences to screen the genome database of Nicotiana benthamiana, we identified two cDNAs encoding the putative tobacco LPCATs (NbLPCAT1 and NbLPCAT2). Both of them were predicted to encode a protein of 463 amino acids with high similarity to LPCATs from other plants. Protein sequence features such as the presence of at least eight putative transmembrane regions, four highly conserved signature motifs and several invariant residues indicate that NbLPCATs belong to the membrane bound O-acyltransferase family. Lysophospholipid acyltransferase activity of NbLPCATs was confirmed by testing lyso-platelet activating factor (lysoPAF) sensitivity through heterologous expression of each full-length cDNA in a yeast mutant Y02431 (lca1?) disrupted in endogenous LPCAT enzyme activity. Analysis of fatty acid profiles of phospholipids from the NbLPCAT-expressing yeast mutant Y02431 cultures supplemented with polyunsaturated fatty acids suggested more incorporation of linoleic acid (18:2n6, LA) and alpha linolenic acid (18:3n3, ALA) into PC compared to yeast mutant harbouring empty vector. In vitro enzymatic assay demonstrated that NbLPCAT1had high lysoPC acyltransferase activity with a clear preference for alpha-linolenoyl-CoA (18:3), while NbLPCAT2 showed a high lysophosphatidic acid (lysoPA) acyltransferase activity towards alpha-linolenoyl-CoA and a weak lysoPC acyltransferase activity. Tissue-specific expression analysis showed a ubiquitous expression of NbLPCAT1 and NbLPCAT2 in roots, stems, leaves, flowers and seeds, and a strong expression in developing flowers. This is the first report on the cloning and characterization of lysophospholipid acyltransferases from N. benthamiana. PMID- 26684753 TI - Placental (pro)renin receptor expression and plasma soluble (pro)renin receptor levels in preeclampsia. AB - INTRODUCTION: The prorenin receptor ((P)RR) contributes to the regulation of the tissue renin-angiotensin system (RAS) and the function of V-ATPase, which are essential for Wnt signaling. Thus, (P)RRs may be involved in the control both of feto-placental and maternal circulation during pregnancy. This study was conducted to clarify how placental (P)RR expression and plasma soluble (P)RR [s(P)RR] levels are associated with blood pressure elevations and renal function during pregnancy. METHODS: We conducted a cross-sectional study, conducted at Saitama medical center in 2010-2013. Preeclamptic women (n = 16) diagnosed according to the criteria of Japan Society of Obstetrics and Gynecology and normotensive pregnant women (n = 15) participated in the study. We measured the expression of (P)RR in the placenta, plasma s(P)RR levels, systolic blood pressure (SBP), and estimated glomerular filtration rate (eGFR). RESULTS: Placental expression of (P)RR was significantly higher in preeclamptic women than in normotensive pregnant women. The plasma s(P)RR levels were significantly higher in preeclamptic women than in normotensive pregnant women. Systolic blood pressure (SBP) was positively correlated with placental (P)RR levels (P = 0.0001) and plasma s(P)RR levels (P = 0.005) in all pregnant women. In preeclamptic women, SBP was positively correlated with placental (P)RR levels (P = 0.004), but not with plasma s(P)RR levels (P = 0.15). The eGFR was negatively correlated with placental (P)RR levels (P = 0.02) and plasma s(P)RR levels (P = 0.0002) in all pregnant women. In preeclamptic women, eGFR was negatively correlated with plasma s(P)RR levels (P = 0.006), but not with placental (P)RR levels (P = 0.93). DISCUSSION: Placental (P)RR can be involved in blood pressure regulation via the tissue RAS. On the other hand, plasma s(P)RR may be involved in the pathogenesis of decreased renal function in preeclampsia. PMID- 26684755 TI - Controlled Oxidation of an NHC-Stabilized Phosphinoaminosilylene with Dioxygen. AB - Reaction of the N-heterocyclic carbene-stabilized phosphinoaminosilylene ArN(SiMe3)Si(I(i)Pr)PPh2 (Ar = 2,6-(i)Pr2C6H3, I(i)Pr = 1,3-diisopropyl-4,5 dimethyl-imidazol-2-ylidene) (2) with dioxygen resulted in the formation of the two products ArN = Si(I(i)Pr)(OSiMe3)(OPPh2) (3) and ArN = Si(I(i)Pr)(OSiMe3)PPh2 (4), and the ratios of the two products can be controlled by the reaction temperatures and dioxygen concentrations. PMID- 26684754 TI - Landscape of gene fusions in epithelial cancers: seq and ye shall find. AB - Enabled by high-throughput sequencing approaches, epithelial cancers across a range of tissue types are seen to harbor gene fusions as integral to their landscape of somatic aberrations. Although many gene fusions are found at high frequency in several rare solid cancers, apart from fusions involving the ETS family of transcription factors which have been seen in approximately 50% of prostate cancers, several other common solid cancers have been shown to harbor recurrent gene fusions at low frequencies. On the other hand, many gene fusions involving oncogenes, such as those encoding ALK, RAF or FGFR kinase families, have been detected across multiple different epithelial carcinomas. Tumor specific gene fusions can serve as diagnostic biomarkers or help define molecular subtypes of tumors; for example, gene fusions involving oncogenes such as ERG, ETV1, TFE3, NUT, POU5F1, NFIB, PLAG1, and PAX8 are diagnostically useful. Tumors with fusions involving therapeutically targetable genes such as ALK, RET, BRAF, RAF1, FGFR1-4, and NOTCH1-3 have immediate implications for precision medicine across tissue types. Thus, ongoing cancer genomic and transcriptomic analyses for clinical sequencing need to delineate the landscape of gene fusions. Prioritization of potential oncogenic "drivers" from "passenger" fusions, and functional characterization of potentially actionable gene fusions across diverse tissue types, will help translate these findings into clinical applications. Here, we review recent advances in gene fusion discovery and the prospects for medicine. PMID- 26684756 TI - Generation of a Novel Bacteriophage Library Displaying scFv Antibody Fragments from the Natural Buffalo Host to Identify Antigens from Adult Schistosoma japonicum for Diagnostic Development. AB - The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11-12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis. The enriched libraries were used to probe a schistosome specific protein microarray resulting in the recognition of a number of proteins, five of which were specific to schistosomes, with RNA expression predominantly in the adult life-stage based on interrogation of schistosome expressed sequence tags (EST). As the libraries were enriched by panning against ES products, these antigens may be excreted or secreted into the host vasculature and hence may make good targets for a diagnostic assay. Further selection of the scFv library against infected mouse sera identified five soluble scFv clones that could selectively recognise soluble whole adult preparations (SWAP) relative to an irrelevant protein control (ovalbumin). Furthermore, two of the identified scFv clones also selectively recognised SWAP proteins when spiked into naive mouse sera. These host B-cell derived scFvs that specifically bind to schistosome protein preparations will be valuable reagents for further development of a cost effective point-of-care diagnostic test. PMID- 26684757 TI - Mannose-binding lectin protein and its association to clinical outcomes in COPD: a longitudinal study. AB - BACKGROUND: Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort. METHODS: We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter. Patients were dichotomized as frequent (>= 2 AECOPD/year) or infrequent exacerbators. Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline. RESULTS: The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95% CI, 1.24 7.14, p = 0.01). The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]). Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum. However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test). CONCLUSIONS: In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival. The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989. PMID- 26684758 TI - Systematic review of the validity and reliability of consumer-wearable activity trackers. AB - BACKGROUND: Consumer-wearable activity trackers are electronic devices used for monitoring fitness- and other health-related metrics. The purpose of this systematic review was to summarize the evidence for validity and reliability of popular consumer-wearable activity trackers (Fitbit and Jawbone) and their ability to estimate steps, distance, physical activity, energy expenditure, and sleep. METHODS: Searches included only full-length English language studies published in PubMed, Embase, SPORTDiscus, and Google Scholar through July 31, 2015. Two people reviewed and abstracted each included study. RESULTS: In total, 22 studies were included in the review (20 on adults, 2 on youth). For laboratory based studies using step counting or accelerometer steps, the correlation with tracker-assessed steps was high for both Fitbit and Jawbone (Pearson or intraclass correlation coefficients (CC) > =0.80). Only one study assessed distance for the Fitbit, finding an over-estimate at slower speeds and under estimate at faster speeds. Two field-based studies compared accelerometry assessed physical activity to the trackers, with one study finding higher correlation (Spearman CC 0.86, Fitbit) while another study found a wide range in correlation (intraclass CC 0.36-0.70, Fitbit and Jawbone). Using several different comparison measures (indirect and direct calorimetry, accelerometry, self-report), energy expenditure was more often under-estimated by either tracker. Total sleep time and sleep efficiency were over-estimated and wake after sleep onset was under-estimated comparing metrics from polysomnography to either tracker using a normal mode setting. No studies of intradevice reliability were found. Interdevice reliability was reported on seven studies using the Fitbit, but none for the Jawbone. Walking- and running-based Fitbit trials indicated consistently high interdevice reliability for steps (Pearson and intraclass CC 0.76-1.00), distance (intraclass CC 0.90-0.99), and energy expenditure (Pearson and intraclass CC 0.71-0.97). When wearing two Fitbits while sleeping, consistency between the devices was high. CONCLUSION: This systematic review indicated higher validity of steps, few studies on distance and physical activity, and lower validity for energy expenditure and sleep. The evidence reviewed indicated high interdevice reliability for steps, distance, energy expenditure, and sleep for certain Fitbit models. As new activity trackers and features are introduced to the market, documentation of the measurement properties can guide their use in research settings. PMID- 26684760 TI - Prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance--protocol for a systematic review. AB - BACKGROUND: Testicular cancer is primarily treated with the surgical removal of the affected testis. About 50% of testicular cancer patients present with a stage I seminoma. If no chemo- or radiotherapy as adjuvant treatment is initiated after orchiectomy, 15-20% of these patients will develop metastases. Although adjuvant treatment is effective in reducing the relapse risk, there is rising concern about overtreatment of these patients. Prognostic factors at primary diagnosis might have the potential to identify patients at higher risk of tumor relapse, allowing to guide individual therapy and to avoid overtreatment. Therefore, we aim to synthesize the available evidence on tumor or patient characteristics as possible prognostic factors for cancer recurrence in patients with clinical stage I seminoma. METHODS/DESIGN: We will conduct a broad systematic review to analyze what prognostic factors predict cancer recurrence in patients with a first time diagnosis of clinical stage I seminoma, who received no adjuvant chemo- or radiotherapy after orchiectomy. The literature search will comprise MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the conference proceedings of the American Society of Clinical Oncology (ASCO), American Urologic Association (AUA), and European Urologic Association (EAU) Annual Meetings. Prospective and retrospective longitudinal studies reporting on prognostic factors for cancer recurrence will be considered. We will consider the wealth of any candidate clinical or pathological prognostic factor reported in the literature. Our outcome of interest will be tumor recurrence at a minimum of 2 years follow-up. Study screening, data extraction, and quality assessment will be done by two reviewers independently. Hazard ratios will be used to measure the relationship between the potential prognostic factor and tumor recurrence. Meta analyses will be conducted with sufficiently homogeneous studies and separately with respect to study design, by using the random-effects generic inverse variance model. DISCUSSION: Limitations and strengths will be discussed in our review, and the results will be put into context with other studies in this field. Our results will help to guide evidence-based decision-making on patients with clinical stage I seminoma, allowing a better adjustment of therapies with regard to the individual patient's risk. Our findings will furthermore help to formulate recommendations for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009434. PMID- 26684759 TI - The Diagnostic Value of Neuropathy Symptom and Change Score, Neuropathy Impairment Score and Michigan Neuropathy Screening Instrument for Diabetic Peripheral Neuropathy. AB - AIMS: This study aims to evaluate the diagnostic capabilities of neuropathy symptom and change (NSC) score, neuropathy impairment score (NIS) and Michigan neuropathy screening instrument (MNSI) in diagnosing diabetic peripheral neuropathy (DPN). METHODS: A total of 131 patients with type II diabetes received NSC, NIS and MNSI scoring systems. Electromyography/nerve conduction velocity (EMG/NCV) test was taken as gold standard. Correlations between EMG/NCV test and the 3 scorings, and their sensitivity, specificity, positive and negative predictive values, accuracy and kappa (x03BA;) value were analyzed. RESULTS: The prevalence of DPN was 43.5% according to EMG/NCV findings. EMG/NCV test was significantly positive correlated with all the 3 scorings, highest with NIS scoring (r = 0.653, p < 0.001). Compared with EMG/NCV test, NSC score was most sensitive (85.96%) but least specific (77.03%); NIS score had lower sensitivity (59.65%) but best specificity (98.65%) and accuracy (81.68%). Both had high concordance with EMG/NCV test (x03BA; = 0.61). Sensitivity, specificity and accuracy of MNSI were highest (70.18, 98.65 and 80.15%) at the cutoff values of >1.0, >2.5 and >1.5, respectively (x03BA; = 0.58). CONCLUSIONS: Both NSC and NIS were accurate and reliable diagnostic methods for DPN. The combined application of NSC and NIS was recommended in DPN diagnosis. PMID- 26684761 TI - Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long term tumor control in patients with craniopharyngioma. AB - OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and subsequent treatment was 1.67 +/- 1.50 years (mean +/- SD). CONCLUSIONS In this small but focused population, P32 treatment provided limited local control for cyst growth. Brachytherapy alone did not reliably avert the need for subsequent surgery or EBR. PMID- 26684762 TI - Predictors of delayed recovery following pediatric sports-related concussion: a case-control study. AB - OBJECT Pediatric sports-related concussions are a growing public health concern. The factors that determine injury severity and time to recovery following these concussions are poorly understood. Previous studies suggest that initial symptom severity and diagnosis of attention deficit hyperactivity disorder (ADHD) are predictors of prolonged recovery (> 28 days) after pediatric sports-related concussions. Further analysis of baseline patient characteristics may allow for a more accurate prediction of which patients are at risk for delayed recovery after a sports-related concussion. METHODS The authors performed a single-center retrospective case-control study involving patients cared for at the multidisciplinary Concussion Clinic at Children's of Alabama between August 2011 and January 2013. Patient demographic data, medical history, sport concussion assessment tool 2 (SCAT2) and symptom severity scores, injury characteristics, and patient balance assessments were analyzed for each outcome group. The control group consisted of patients whose symptoms resolved within 28 days. The case group included patients whose symptoms persisted for more than 28 days. The presence or absence of the SCAT2 assessment had a modifying effect on the risk for delayed recovery; therefore, stratum-specific analyses were conducted for patients with recorded SCAT2 scores and for patients without SCAT2 scores. Unadjusted ORs and adjusted ORs (aORs) for an association of delayed recovery outcome with specific risk factors were calculated with logistic regression analysis. RESULTS A total of 294 patients met the inclusion criteria of the study. The case and control groups did not statistically significantly differ in age (p = 0.7). For the patients who had received SCAT2 assessments, a previous history of concussion (aOR 3.67, 95% CI 1.51-8.95), presenting SCAT2 score < 80 (aOR 5.58, 95% CI 2.61-11.93), and female sex (aOR 3.48, 95% CI 1.43-8.49) were all associated with a higher risk for postconcussive symptoms lasting more than 28 days. For patients without SCAT2 scores, female sex and reporting a history of ADHD significantly increased the odds of prolonged recovery (aOR 4.41, 95% CI 1.93-10.07 and aOR 3.87, 95% CI 1.13-13.24, respectively). Concussions resulting from playing a nonhelmet sport were also associated with a higher risk for prolonged symptoms in patients with and without SCAT2 scores (OR 2.59, 95% CI 1.28-5.26 and OR 2.17, 95% CI 0.99-7.73, respectively). Amnesia, balance abnormalities, and a history of migraines were not associated with symptoms lasting longer than 28 days. CONCLUSIONS This case-control study suggests candidate risk factors for predicting prolonged recovery following sports-related concussion. Large prospective cohort studies of youth athletes examined and treated with standardized protocols will be needed to definitively establish these associations and confirm which children are at highest risk for delayed recovery. PMID- 26684763 TI - A new Hydrocephalus Clinical Research Network protocol to reduce cerebrospinal fluid shunt infection. AB - OBJECT In a previous report by the same research group (Kestle et al., 2011), compliance with an 11-step protocol was shown to reduce CSF shunt infection at Hydrocephalus Clinical Research Network (HCRN) centers (from 8.7% to 5.7%). Antibiotic-impregnated catheters (AICs) were not part of the protocol but were used off protocol by some surgeons. The authors therefore began using a new protocol that included AICs in an effort to reduce the infection rate further. METHODS The new protocol was implemented at HCRN centers on January 1, 2012, for all shunt procedures (excluding external ventricular drains [EVDs], ventricular reservoirs, and subgaleal shunts). Procedures performed up to September 30, 2013, were included (21 months). Compliance with the protocol and outcome events up to March 30, 2014, were recorded. The definition of infection was unchanged from the authors' previous report. RESULTS A total of 1935 procedures were performed on 1670 patients at 8 HCRN centers. The overall infection rate was 6.0% (95% CI 5.1% 7.2%). Procedure-specific infection rates varied (insertion 5.0%, revision 5.4%, insertion after EVD 8.3%, and insertion after treatment of infection 12.6%). Full compliance with the protocol occurred in 77% of procedures. The infection rate was 5.0% after compliant procedures and 8.7% after noncompliant procedures (p = 0.005). The infection rate when using this new protocol (6.0%, 95% CI 5.1%-7.2%) was similar to the infection rate observed using the authors' old protocol (5.7%, 95% CI 4.6%-7.0%). CONCLUSIONS CSF shunt procedures performed in compliance with a new infection prevention protocol at HCRN centers had a lower infection rate than noncompliant procedures. Implementation of the new protocol (including AICs) was associated with a 6.0% infection rate, similar to the infection rate of 5.7% from the authors' previously reported protocol. Based on the current data, the role of AICs compared with other infection prevention measures is unclear. PMID- 26684764 TI - Hemorrhagic presentations of cerebellar pilocytic astrocytomas in children resulting in death: report of 2 cases. AB - Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration. As examples, we describe two cases of fatal hemorrhagic cerebellar PAs: one of a child with a slowly growing stereotypical WHO Grade I PA with a 1-year period of symptomatology that preceded a rapid clinical deterioration, and another of an asymptomatic child having a PA variant, presenting with progressive obtundation following a presumed Valsalva event. These two scenarios parallel previous reports in the literature of either a setting of progressive expression of cerebellar dysfunction and transient episodes of raised intracranial pressure (ICP), or abrupt onset of features of increased ICP in a previously well child. The literature is further reviewed for a current understanding of the factors that predispose, initiate and propagate bleeding, with specific reference to the role of vascular endothelial growth factor and other angiogenic agents in the genesis and stability of the vasculature in PAs. In this context, we propose that obliterative vascular mural hyalinization with associated altered flow dynamics and microaneurysm formation was the pathogenesis of the hemorrhage in our first case. In the second case, large tumor size, increased growth rate, looseness of the background myxoid matrix, and thinness of the tumor blood vessels with calcospherite deposition predisposed to vascular leakage and bleeding concurrent with sudden increases in intravascular hydrostatic pressure. In that cerebellar PAs are common, this report underscores the importance of considering in the differential diagnosis the possibility of a spontaneous hemorrhage in a posterior fossa PA in a child presenting with a sudden neurological ictus and raised ICP. PMID- 26684765 TI - Return to the emergency department after ventricular shunt evaluation. AB - OBJECT Patients with CSF shunts are medically complex and frequently present to the emergency department (ED) with suspected shunt malfunction. After adequate evaluation in the ED and proper disposition, some patients return to the ED within a short period of time. In this study, the authors examined the reasons for ED revisits within 7 days of the index ED visit to discern possible preventable returns. METHODS There were 3080 index ED visits made by patients with shunted hydrocephalus between 2010 and 2013. Index ED visits preceded by another ED visit or neurosurgical procedure within 60 days were excluded. Index ED visits for reasons unrelated to shunt function and those that led directly to admissions and shunt revision surgeries were also excluded. The remaining 1509 ED visits were eligible for analysis in this study. Final dispositions from the index ED visit included home (1176 cases), admission to the neurosurgery service for observation (134 cases), and admission to other services (199 cases). Subsequent events within 7 days, including ED revisits, hospital admissions, and shunt-related surgery were recorded, and reasons for the ED revisits were categorized based on whether the visit was related to shunt function concerns. Clinical and socioeconomic factors were analyzed for their association with ED revisits by using statistical methods. RESULTS Of the 1176 patients discharged home from the ED after shunt function evaluation, 101 (8.6%) returned to the ED within 7 days. Of the 134 patients admitted to the neurosurgery service for observation only, 8 (6.0%) returned to the ED within 7 days of discharge. Of the 199 patients admitted to hospital services other than neurosurgery, 13 (6.5%) returned to the ED within 7 days of discharge. The reasons for ED revisits vary (total of 122 visits combining the 3 groups), but at least 60% of the revisits were clearly unrelated to shunt function. A younger age, daytime arrival to the ED, and living within the metropolitan area were identified as risk factors for ED revisits. CONCLUSIONS Children with CSF shunts are medically complex and use ED services often. After an index ED visit at which shunt function was deemed to be the chief concern, the purpose of the subsequent return to the ED within 7 days was often for complaints unrelated to shunt function. Caution is warranted when attempting to classify these complex patients as having potential preventable return-to-system events. PMID- 26684766 TI - Normalization of brain morphology after surgery in sagittal craniosynostosis. AB - OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 * 1.05 * 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty performed at an early age offers substantial brain normalization by adolescence, but also that some effects of vault constriction may still persist after treatment. Specifically, few areas of expansion in frontoparietal and temporooccipital regions may persist. Overall, data from this small cohort support the primary goal of surgery in allowing for more normalized brain growth. Larger samples, and correlating degree of normalization with cognitive performance in NSC, are warranted. PMID- 26684767 TI - The influence of central review on outcome in malignant gliomas of the spinal cord: the CCG-945 experience. AB - OBJECT The impact of central pathology review on outcome has been described in pediatric patients with high-grade glioma (HGG). The objective of this report was to analyze the impact of the central pathology review on outcome in the subgroup of patients with institutional diagnosis of HGG of the spinal cord enrolled in the Children's Cancer Group 945 cooperative study. METHODS Five neuropathologists centrally reviewed the pathology of the 18 patients with HGG of the spinal cord who were enrolled in the study. These reviews were independent, and reviewers were blinded to clinical history and outcomes. A consensus diagnosis was established for each patient, based on the outcome of the review. RESULTS Of 18 patients, only 10 were confirmed to have HGG on central review. At a median follow-up of 12 years, event-free and overall survival for all 18 patients was 43.2% +/- 13.3% and 50% +/- 13.4%, respectively. After central review, 10-year event-free and overall survival for confirmed HGGs and discordant diagnoses was 30% +/- 12.5% versus 58.3% +/- 18.8% (p = 0.108) and 30% +/- 12.5% versus 75% +/- 14.2% (p = 0.0757), respectively. CONCLUSIONS The level of discordant diagnoses in children and adolescents with institutional diagnosis of HGG of the spinal cord was 44% in this experience. However, there was no significant difference in outcome between patients with confirmed and discordant diagnosis. This group of tumor deserves a specific attention in future trials. PMID- 26684768 TI - Development and initial evaluation of a finite element model of the pediatric craniocervical junction. AB - OBJECT There is a significant deficiency in understanding the biomechanics of the pediatric craniocervical junction (CCJ) (occiput-C2), primarily because of a lack of human pediatric cadaveric tissue and the relatively small number of treated patients. To overcome this deficiency, a finite element model (FEM) of the pediatric CCJ was created using pediatric geometry and parameterized adult material properties. The model was evaluated under the physiological range of motion (ROM) for flexion-extension, axial rotation, and lateral bending and under tensile loading. METHODS This research utilizes the FEM method, which is a numerical solution technique for discretizing and analyzing systems. The FEM method has been widely used in the field of biomechanics. A CT scan of a 13-month old female patient was used to create the 3D geometry and surfaces of the FEM model, and an open-source FEM software suite was used to apply the material properties and boundary and loading conditions and analyze the model. The published adult ligament properties were reduced to 50%, 25%, and 10% of the original stiffness in various iterations of the model, and the resulting ROMs for flexion-extension, axial rotation, and lateral bending were compared. The flexion extension ROMs and tensile stiffness that were predicted by the model were evaluated using previously published experimental measurements from pediatric cadaveric tissues. RESULTS The model predicted a ROM within 1 standard deviation of the published pediatric ROM data for flexion-extension at 10% of adult ligament stiffness. The model's response in terms of axial tension also coincided well with published experimental tension characterization data. The model behaved relatively stiffer in extension than in flexion. The axial rotation and lateral bending results showed symmetric ROM, but there are currently no published pediatric experimental data available for comparison. The model predicts a relatively stiffer ROM in both axial rotation and lateral bending in comparison with flexion-extension. As expected, the flexion-extension, axial rotation, and lateral bending ROMs increased with the decrease in ligament stiffness. CONCLUSIONS An FEM of the pediatric CCJ was created that accurately predicts flexion-extension ROM and axial force displacement of occiput-C2 when the ligament material properties are reduced to 10% of the published adult ligament properties. This model gives a reasonable prediction of pediatric cervical spine ligament stiffness, the relationship between flexion-extension ROM, and ligament stiffness at the CCJ. The creation of this model using open-source software means that other researchers will be able to use the model as a starting point for research. PMID- 26684769 TI - Additive partitioning of a beta diversity index is controversial. PMID- 26684770 TI - Turning statistical physics models into materials design engines. AB - Despite the success statistical physics has enjoyed at predicting the properties of materials for given parameters, the inverse problem, identifying which material parameters produce given, desired properties, is only beginning to be addressed. Recently, several methods have emerged across disciplines that draw upon optimization and simulation to create computer programs that tailor material responses to specified behaviors. However, so far the methods developed either involve black-box techniques, in which the optimizer operates without explicit knowledge of the material's configuration space, or require carefully tuned algorithms with applicability limited to a narrow subclass of materials. Here we introduce a formalism that can generate optimizers automatically by extending statistical mechanics into the realm of design. The strength of this approach lies in its capability to transform statistical models that describe materials into optimizers to tailor them. By comparing against standard black-box optimization methods, we demonstrate how optimizers generated by this formalism can be faster and more effective, while remaining straightforward to implement. The scope of our approach includes possibilities for solving a variety of complex optimization and design problems concerning materials both in and out of equilibrium. PMID- 26684771 TI - Reply to Chen and Schmera: Partitioning beta diversity into replacement and nestedness-resultant components is not controversial. PMID- 26684772 TI - Re-treatment rates after treatment with the Pipeline Embolization Device alone versus Pipeline and coil embolization of cerebral aneurysms: a single-center experience. AB - OBJECT The optimal strategy for use of the Pipeline Embolization Device (PED, ev3 Neurovascular) has not been clearly defined. The authors examined re-treatment rates after treatment with PED alone versus PED and adjunctive coil embolization (PED/coil). METHODS The authors retrospectively examined cerebral aneurysms treated with the PED from May 2011 to March 2014. Overall, 133 patients (25 men, 108 women; mean age 60.4 years, range 23-85 years) were treated for 140 aneurysms (mean size 11.8 +/- 8.3 mm) requiring 224 PEDs (mean 1.7 PEDs per patient). Sixty eight patients (13 men, 55 women) were treated with PED alone for 73 aneurysms (mean size 10.6 +/- 9.2 mm) and 65 patients (12 men, 53 women) were treated with PED/coil for 67 aneurysms (mean size 12.8 +/- 7.4 mm). RESULTS Eight aneurysms in 8 patients were re-treated in the PED-alone cohort versus only 1 aneurysm in 1 patient in the PED/coil cohort for re-treatment rates of 11.8% (8/68) and 1.5% (1/65), respectively (p = 0.03). Two patients in the PED-alone cohort were re treated due to PED contraction, while the other 6 were re-treated for persistent filling of the aneurysms. The PED/coil patient experienced continued filling of a vertebrobasilar artery aneurysm. No aneurysms in either group ruptured after treatment. CONCLUSIONS Adjunctive coil embolization during flow diversion with the PED resulted in a significantly lower re-treatment rate compared with PED alone, suggesting an added benefit with adjunctive coil embolization. This result may provide the basis for future evaluation with randomized, controlled trials. PMID- 26684773 TI - Diagnosis of a growing radiation-induced skull lesion in a patient: an unusual scar. AB - New lesions arising from within an area of previous irradiation often present a diagnostic dilemma, with new malignancy or metastasis of particular concern. The authors report a case of reactive fibroblast proliferation emerging from a previous radiation field and presenting as a growing lesion of the frontal and parietal skull. Following complete gross resection of the skull lesion and histopathological analysis, it was discovered that this lesion consisted of dense fibroblast proliferation with areas of osteonecrosis. This unusual reactive phenomenon offers a novel differential diagnosis for a new contrast-enhancing lesion in a region of previous radiation. PMID- 26684774 TI - A preliminary study of the clinical application of optic pathway diffusion tensor tractography in suprasellar tumor surgery: preoperative, intraoperative, and postoperative assessment. AB - OBJECT Visual impairments are the most common objective manifestations of suprasellar lesions. Diffusion tensor imaging (DTI) is a noninvasive MRI modality that depicts the subcortical white matter tracts in vivo. In this study the authors tested the value of visual pathway tractography in comparison with visual field and visual acuity analyses. METHODS This prospective study consisted of 25 patients with progressive visual impairment due to suprasellar mass lesions and 6 control patients with normal vision without such lesions. Visual acuity, visual field, and the optic fundus were examined preoperatively and repeated 1 week and 3 months after surgery. Visual pathway DTI tractography was performed preoperatively, intraoperatively immediately after tumor resection, and 1 week and 3 months after surgery. RESULTS In the control group, pre- and postoperative visual status were normal and visual pathway tractography revealed fibers crossing the optic chiasm without any alteration. In patients with suprasellar lesions, vision improved in 24 of 25. The mean distance between optic tracts in tractography decreased after tumor resection and detectable fibers crossing the optic chiasm increased from 12% preoperatively to 72% postoperatively 3 months after tumor resection, and undetectable fibers crossing the optic chiasm decreased from 88% preoperatively to 27% postoperatively 3 months after tumor resection. Visual improvement after tumor removal 1 week and 3 months after surgery was significantly correlated with the distance between optic tracts in intraoperative tractography (p < 0.01). CONCLUSIONS Visual pathway DTI tractography appears to be a promising adjunct to the standard clinical and paraclinical visual examinations in patients with suprasellar mass lesions. The intraoperative findings, in particular the distance between optic tract fibers, can predict visual outcome after tumor resection. Furthermore, postoperative application of this technique may be useful in following anterior optic pathway recovery. PMID- 26684775 TI - Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial. AB - OBJECT This report describes the stereotactic technique, hospitalization, and 90 day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 +/- 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 +/- 1.0 mm (range 3.0-7.9 mm), y = 9.6 +/- 0.9 mm (range 8.0-11.6 mm), z = -7.5 +/- 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 +/- 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 +/- 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 ( clinicaltrials.gov ). PMID- 26684776 TI - Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time. AB - OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 +/- 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 +/- 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% +/- 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% +/- 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures. PMID- 26684778 TI - Letter to the Editor: Intraoperative detection of glioma cells by flow cytometry. PMID- 26684777 TI - Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome. AB - OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS. PMID- 26684779 TI - Pseudotumor-like syndrome and cerebrospinal fluid leak in meningiomas involving the posterior third of the superior sagittal sinus: report of 4 cases. AB - Meningiomas that partially or completely occlude the superior sagittal sinus may create a pseudotumor-like syndrome in certain patients. These patients may have impaired CSF absorption as a result of higher proximal venous pressure. Higher pressures after resection may encumber adequate wound healing and worsen symptoms. Here, the authors present a small series of patients with meningiomas involving the posterior third of the superior sagittal sinus, with documented high intracranial pressure prior to surgery. This paper aims to address the proposed etiology of high intracranial pressure in these patients and its associated complications, including CSF leak, wound dehiscence, pressure-related headaches, and visual complaints. In this paper, the authors propose a management plan to avoid wound complications and pseudotumor-related complications. When considering surgical intervention for patients with compromise of the posterior third of the superior sagittal sinus, careful attention must be paid to addressing potentially elevated intracranial pressure perioperatively. PMID- 26684780 TI - Connectivity of the frontal and anterior insular network: a cortico-cortical evoked potential study. AB - OBJECT The frontal and insular fiber network in humans remains largely unknown. This study investigated the connectivity of the frontal and anterior insular network in humans using cortico-cortical evoked potential (CCEP). METHODS This retrospective analysis included 18 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography and CCEP. Alternating 1-Hz electrical stimuli were delivered to parts of the frontal lobe and anterior insula (prefrontal cortex [PFC], ventrolateral and dorsolateral premotor area [vPM and dPM, respectively], presupplementary motor area [pre-SMA], SMA, frontal operculum, and anterior insula). A total of 40-60 stimuli were averaged in each trial to obtain CCEP responses. The distribution of CCEP was evaluated by calculating the root mean square of CCEP responses. RESULTS Stimulation of the PFC elicited prominent CCEP responses in the medial PFC and PMs over the ipsilateral hemisphere. Stimulation of the vPM and dPM induced CCEP responses in the ipsilateral frontoparietal areas. Stimulation of the pre-SMA induced CCEP responses in the ipsilateral medial and lateral frontal areas and contralateral pre-SMA, whereas stimulation of the SMA induced CCEP responses in the bilateral frontoparietal areas. Stimulation of the frontal operculum induced CCEP responses in the ipsilateral insula and temporal operculum. CCEPs were observed in the ipsilateral medial, lateral frontal, and frontotemporal operculum in the anterior insular stimulation. Stimulation of the vPM and SMA led to the network in the dominant hemisphere being more developed. CONCLUSIONS Various regions within the frontal lobe and anterior insula were linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles. PMID- 26684781 TI - Optic nerve mobilization to enhance the exposure of the pituitary stalk during craniopharyngioma resection: early experience. AB - OBJECT Preservation of the pituitary stalk and its vasculature is a key step in good postoperative endocrinological outcome in patients with craniopharyngiomas. In this article, the authors describe the surgical technique of medial optic nerve mobilization for better inspection and preservation of the pituitary stalk. METHODS This operative technique has been applied in 3 patients. Following tumor exposure via a frontolateral approach, the pituitary stalk could be seen partially hidden under the optic nerve and the optic chiasm. The subchiasmatic and opticocarotid spaces were narrow, and tumor dissection from the pituitary stalk under direct vision was not possible. The optic canal was therefore unroofed, the falciform ligament was incised, and the lateral part of the tuberculum sellae was drilled medial to the optic nerve. The optic nerve could be mobilized medially to widen the opticocarotid triangle, which enhanced visualization of and access to the pituitary stalk. RESULTS By using the optic nerve mobilization technique, the tumor could be removed completely, and the pituitary stalk and its vasculature were preserved in all patients. In 2 patients, vision improved after surgery, while in 1 patient it remained normal, as it was before surgery. The hormonal status remained normal after surgery in 2 patients. In the patient with preoperative hormonal deficiencies, improvement occurred early after surgery and hormonal levels were normal after 3 months. No approach-related complications occurred. CONCLUSIONS This early experience shows that this technique is safe and could be used as a complementary step during microsurgery of craniopharyngiomas. It allows for tumor dissection from the pituitary stalk under direct vision. The pituitary stalk can thus be preserved without jeopardizing the optic nerve. PMID- 26684782 TI - Long-term outcomes of intradural cervical dorsal root rhizotomy for refractory occipital neuralgia. AB - OBJECT Occipital neuralgia (ON) causes chronic pain in the cutaneous distribution of the greater and lesser occipital nerves. The long-term efficacy of cervical dorsal root rhizotomy (CDR) in the management of ON has not been well described. The authors reviewed their 14-year experience with CDR to assess pain relief and functional outcomes in patients with medically refractory ON. METHODS A retrospective chart review of 75 ON patients who underwent cervical dorsal root rhizotomy, from 1998 to 2012, was performed. Fifty-five patients were included because they met the International Headache Society's (IHS) diagnostic criteria for ON, responded to CT-guided nerve blocks at the C-2 dorsal nerve root, and had at least one follow-up visit. Telephone interviews were additionally used to obtain data on patient satisfaction. RESULTS Forty-two patients (76%) were female, and the average age at surgery was 46 years (range 16-80). Average follow up was 67 months (range 5-150). Etiologies of ON included the following: idiopathic (44%), posttraumatic (27%), postsurgical (22%), post-cerebrovascular accident (4%), postherpetic (2%), and postviral (2%). At last follow-up, 35 patients (64%) reported full pain relief, 11 (20%) partial relief, and 7 (16%) no pain relief. The extent of pain relief after CDR was not significantly associated with ON etiology (p = 0.43). Of 37 patients whose satisfaction-related data were obtained, 25 (68%) reported willingness to undergo repeat surgery for similar pain relief, while 11 (30%) reported no such willingness; a single patient (2%) did not answer this question. Twenty-one individuals (57%) reported that their activity level/functional state improved after surgery, 5 (13%) reported a decline, and 11 (30%) reported no difference. The most common acute postoperative complications were infections in 9% (n = 5) and CSF leaks in 5% (n = 3); chronic complications included neck pain/stiffness in 16% (n = 9) and upper-extremity symptoms in 5% (n = 3) such as trapezius weakness, shoulder pain, and arm paresthesias. CONCLUSIONS Cervical dorsal root rhizotomy provides an efficacious means for pain relief in patients with medically refractory ON. In the appropriately selected patient, it may lead to optimal outcomes with a relatively low risk of complications. PMID- 26684783 TI - Direct visualization of improved optic nerve pial vascular supply following tuberculum meningioma resection: case report. AB - Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery. The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome. The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort. PMID- 26684784 TI - Effect of resident handoffs on length of hospital and intensive care unit stay in a neurosurgical population: a cohort study. AB - OBJECT Handoffs and services changes are potentially modifiable sources of medical error and delays in transition of care. This cohort study assessed the relationship between resident service handoffs and length of stay for neurosurgical patients. METHODS All patients admitted to the University of Alabama at Birmingham neurosurgical service between July 1, 2012, and July 1, 2014, were retrospectively identified. A service handoff was defined as any point when a resident handed off coverage of a service for longer than 1 weekend. A conditional probability distribution was constructed to adjust length of stay for the increasing probability of a random handoff. The Student t-test and ANCOVA were used to assess relationships between resident service handoffs and length of hospital stay, adjusted for potential confounders. RESULTS A total of 3038 patients met eligibility criteria and were included in the statistical analyses. Adjusted length of hospital stay (5.32 vs 3.53 adjusted days) and length of ICU stay (4.38 vs 2.96 adjusted days) were both longer for patients who experienced a service handoff, with no difference in mortality. In the ANCOVA model, resident service handoff remained predictive of both length of hospital stay (p < 0.001) and length of ICU stay (p < 0.001). CONCLUSIONS Occurrence of a resident service handoff is an independent predictor of length of hospital and ICU stay in neurosurgical patients. This finding is novel in the neurosurgical literature. Future research might identify mechanisms for improving continuity of care and mitigating the effect of resident handoffs on patient outcomes. PMID- 26684785 TI - Letter to the Editor: Nonsurgical acute traumatic subdural hematoma. PMID- 26684786 TI - Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage. AB - OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain. PMID- 26684787 TI - Living Long and Living Well: Results from the Women's Health Initiative. PMID- 26684788 TI - Low back pain and fevers. PMID- 26684789 TI - Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients. AB - BACKGROUND: Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil. METHODS: CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1beta, IL-6, TNF-alpha, IL-12, IFN-alpha, IFN-gamma, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15). RESULTS: We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-alpha, IL-6, IFN-alpha, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-alpha>IFN-alpha were the best respective HAART segregation biomarkers. CONCLUSION: HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group. PMID- 26684791 TI - Percutaneous coronary intervention of an iatrogenic occlusion of the circumflex coronary artery after mitral valve replacement. AB - Occlusion of the circumflex coronary artery by compromising sutures is a serious complication in patients undergoing mitral valve replacement. The majority of such patients have to undergo bypass surgery or redo mitral valve replacement. We report a case of an iatrogenic occlusion of the circumflex coronary artery after mitral valve replacement that was treated by percutaneous coronary intervention. PMID- 26684790 TI - The Health Impact of Upward Mobility: Does Socioeconomic Attainment Make Youth More Vulnerable to Stressful Circumstances? AB - Previous research has documented that adolescent stressful life experiences have a long-term detrimental influence on cardio-metabolic disease risk. While studies have focused on either the moderating or mediating effects of youth socioeconomic competence, drawing from a life course perspective, we estimate these mediating and moderating effects simultaneously within a single analytical framework. The study used a nationally representative sample of 11,271 adolescents (53 % female) over 13 years. The sample included 49 % minority youth (21 % Blacks, 16 % Hispanics, 6 % Asians, 4 % multiracial youth, and 2 % Native Americans). The analyses focused specifically on adolescents' stressful life experiences, their socioeconomic development (conceptualized as their future orientation in adolescence as well as their educational attainment and income in young adulthood), and cardio-metabolic disease risk in young adulthood (assessed by a measure of allostatic load consisting of nine regulatory bio-markers). The study findings indicated detrimental influences of stressful life experiences on both socioeconomic development and young adult cardio-metabolic disease risk and a beneficial additive influence of positive socioeconomic development on young adult cardio-metabolic health. However, there was also evidence that striving for socioeconomic attainment increased the detrimental influence of stressful life experiences on young adult cardio-metabolic health. These study findings have important implications for our understanding about youth resilience in relation to stressful life contexts and for the formulation of policies and programs for promoting youth health. PMID- 26684792 TI - Sphingolipids in Major Depression. AB - Major depression is one of the most common and severe diseases affecting the world's population. However, the pathogenesis of the disease remains inadequately defined. Previously, a lack of monoaminergic neurotransmitters was the focus of pathophysiological concepts; however, recent concepts focus on a alteration of neurogenesis in the hippocampus. This concept suggests that neurogenesis is decreased in major depression with a rarefication of neuronal networks and a lack of new, immature neurons in the hippocampus, events that may result in the clinical symptoms of major depression. However, molecular targets involved in the pathogenesis of major depression and, in particular, a reduction of neurogenesis, are largely unknown. We have recently discovered that an inhibition of the acid sphingomyelinase/ceramide system mediates the effects of tri- and tetracyclic antidepressants. Moreover, an accumulation of ceramide in the hippocampus results in depression-like symptoms. This suggests the acid sphingomyelinase/ceramide system is very important in the pathogenesis of major depression. PMID- 26684793 TI - Correction: Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection. PMID- 26684794 TI - Crocker, et al.: Reducing barriers to parent participation in pediatric palliative care research. PMID- 26684795 TI - Safety Assessment of Synthetic Fluorphlogopite as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel (the Panel) reviewed the safety of synthetic fluorphlogopite as used in cosmetics. Synthetic fluorphlogopite functions as a bulking agent and a viscosity-increasing agent. The Panel reviewed available animal and human data related to this ingredient along with a previous safety assessment of other magnesium silicates. The Panel concluded that synthetic fluorphlogopite was safe as cosmetic ingredients in the practices of use and concentration as given in this safety assessment. PMID- 26684796 TI - Safety Assessment of Boron Nitride as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of boron nitride which functions in cosmetics as a slip modifier (ie, it has a lubricating effect). Boron nitride is an inorganic compound with a crystalline form that can be hexagonal, spherical, or cubic; the hexagonal form is presumed to be used in cosmetics. The highest reported concentration of use of boron nitride is 25% in eye shadow formulations. Although boron nitride nanotubes are produced, boron nitride is not listed as a nanomaterial used in cosmetic formulations. The Panel reviewed available chemistry, animal data, and clinical data and concluded that this ingredient is safe in the present practices of use and concentration in cosmetic formulations. PMID- 26684797 TI - Safety Assessment of Panax spp Root-Derived Ingredients as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 13 Panax spp root-derived ingredients as used in cosmetics. Panax "spp" indicates that multiple species within the genus are used in cosmetics, but not all species within that genus. Four species are being considered in this safety assessment. These ingredients function mostly as skin-conditioning agents-miscellaneous, fragrance ingredients, skin-conditioning agents-humectant, skin-conditioning agents-emollient, and cosmetic astringents. The Panel reviewed available data related to these ingredients and addressed the issue of pulegone, a constituent of these ingredients and other ingredients, such as peppermint oil. The Panel concluded that these Panax spp root-derived ingredients are safe in the practices of use and concentration as given in this safety assessment. PMID- 26684798 TI - Safety Assessment of Alkyl Ethylhexanoates as Used in Cosmetics. AB - The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 16 alkyl ethylhexanoates for use in cosmetics, concluding that these ingredients are safe in cosmetic formulations in the present practices of use and concentrations when formulated to be nonirritating. The alkyl ethylhexanoates primarily function as skin-conditioning agents in cosmetics. The highest concentration of use reported for any of the alkyl ethylhexanoates is 77.3% cetyl ethylhexanoate in rinse-off formulations used near the eye, and the highest leave on use reported is 52% cetyl ethylhexanoate in lipstick formulations. The Panel reviewed available animal and clinical data related to these ingredients, and the similarities in structure, properties, functions, and uses of ingredients from previous CIR assessments on constituent alcohols that allowed for extrapolation of the available toxicological data to assess the safety of the entire group. PMID- 26684799 TI - Clinical and radiological outcomes following hybrid surgery in the treatment of multi-level cervical spondylosis: over a 2-year follow-up. AB - BACKGROUND: The optimal surgical approach for treatment of multi-level cervical disc disease is currently widely debated. Anterior cervical discectomy and fusion (ACDF) combined with cervical disc arthroplasty (CDA) has been presented as a treatment approach, but to date, there are few reports with adequate clinical and radiological data for this hybrid surgical procedure. The goal of this paper is to assess clinical and radiological outcomes in patients with cervical spondylosis in three contiguous segments after treatment with artificial disc replacement combined with fusion. MATERIALS AND METHODS: We performed a retrospective review of 36 patients (mean age of 48.6 years) with contiguous three-level cervical spondylosis who were treated with ACDF coupled with CDA (hybrid surgery) between October 2008 and October 2012. Clinical evaluation was based on the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and postoperative JOA score improvement rate (IR). Radiographic parameters, angular range of motion (ROM) for C2-C7, and ROM for the superior and inferior adjacent segments were measured before the operation, at 1, 3, 6, and 12 months postoperation, and at the final follow-up evaluation. All cases were followed for at least 28 months (range 28-65 months). RESULTS: All patients exhibited significant postoperative improvement in NDI and JOA scores compared to preoperative levels (P < 0.05), and these improved scores were maintained during the follow-up period. The JOA score improvement rate was 70.83 % at the final follow-up evaluation. The mean C2-C7 ROM of all cases was significantly decreased immediately after operation but recovered to preoperative levels after 12 months (P = 0.721). The ROM of the superior and inferior adjacent segments was recovered to preoperative levels after 6 months (P > 0.05). One patient required a second surgery for symptomatic adjacent segment degeneration. Neither pseudarthrosis nor other device migration was observed in any patients during the entire follow-up period. CONCLUSIONS: These results indicate that hybrid surgery seems to be a promising, acceptable, and alternative surgical approach for the treatment of multi-level cervical disc disease. PMID- 26684800 TI - Silencing of HMGA2 suppresses cellular proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer. AB - The high-mobility group protein A2 (HMGA2) is an architectural transcription factor that plays a crucial role in the development and progression of various malignant cancers. However, the function of HMGA2 in bladder cancer remains largely unknown. Therefore, we aim to investigate the effect of HMGA2 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of bladder cancer cells. The expression of HMGA2 in human bladder cancer cells was downregulated by small interfering RNA (siRNA). The protein levels of HMGA2 and other related proteins were detected by Western blotting. The cell proliferation and apoptosis were examined by Cell Counting Kit-8 and flow cytometry, respectively. Transwell migration and invasion assays were performed to assess the effect of HMGA2 on the migration and invasion ability of cells. In conclusion, we found that HMGA2 knockdown markedly inhibited cell proliferation; this reduced cell growth was due to the high apoptosis rate of cells, as Bcl-xl was diminished, whereas Bax was upregulated. Moreover, our results showed that silencing of HMGA2 in cancer cells greatly inhibited the cell migration and invasion, decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), and affected the occurrence of EMT. We further found that decreased HMGA2 expression suppressed the transforming growth factor-beta (TGF-beta)/Smad and Wnt/beta-catenin signaling pathway in bladder cancer cells. These results revealed that HMGA2 played an important role in the progression of bladder cancer and might be a novel target for therapy in human bladder cancer. PMID- 26684801 TI - RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma. AB - Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF kappaB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-alpha-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3 mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma. PMID- 26684802 TI - Upregulation of connexin43 contributes to PX-12-induced oxidative cell death. AB - Thioredoxin (Trx) is a small redox protein that underlies aggressive tumor growth and resistance to chemotherapy. Inhibition of Trx with the chemical inhibitor PX 12 suppresses tumor growth and induces cell apoptosis. Currently, the mechanism underlying the therapeutic actions of PX-12 and the molecules influencing cell susceptibility to PX-12 are incompletely understood. Given that connexin43 (Cx43), a tumor suppressor, regulates tumor cell susceptibility to chemotherapy, we examined the possible involvement of Cx43 in PX-12-induced cell death. Exposure of cells to PX-12 led to a loss of cell viability, which was associated with the activation of oxidative sensitive c-Jun N-terminal kinase (JNK). Inhibition of JNK or supplement of cells with anti-oxidants prevented the cell killing action of PX-12. The forced expression of Cx43 in normal and tumor cells increased cell sensitivity to PX-12-induced JNK activation and cell death. In contrast, the downregulation of Cx43 with siRNA or the suppression of gap junctions with chemical inhibitors attenuated JNK activation and enhanced cell resistance to PX-12. Further analysis revealed that PX-12 at low concentrations induced a JNK-dependent elevation in the Cx43 protein, which was also preventable by supplementing the cells with anti-oxidants. Our results thus indicate that Cx43 is a determinant in the regulation of cell susceptibility to PX-12 and that the upregulation of Cx43 may be an additional mechanism by which PX-12 exerts its anti-tumor actions. PMID- 26684803 TI - KRAS mutations in pancreatic circulating tumor cells: a pilot study. AB - Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed in a metastatic stage. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic dissemination. We aimed to isolate and characterize CTC to evaluate their significance as prognostic markers in PDAC. Blood obtained from healthy donors and patients with PDAC before therapy was filtered with ScreenCell(r) filtration devices for size-based CTC isolation. Captured cells were analyzed by immunofluorescence for an epithelial to mesenchymal transition (EMT) marker (zinc finger E-box binding homebox 1 (ZEB1)) and an epithelial antigen (cytokeratin (CK)). Molecular analysis of parallel specimens evaluated the KRAS mutation status of the CTC. The survival of each patient after study was recorded. As demonstrated by either cytology or finding of a KRAS mutation, CTC were detected in 18 of 21 patients (86 %) with proven PDAC: 8 out of 10 patients (80 %) with early stage (UICC IIA/IIB) and 10 out of 11 (91 %) with late stage (UICC III/IV) disease. CTC were not found in any of the 10 control patients (p < 0.001). The presence of CTC did not adversely affect median survival: 16 months in CTC positive (n = 18) vs. 10 months in CTC-negative (n = 3) patients. Neither ZEB1 nor cytological characteristics correlated with overall survival, although ZEB1 was found almost exclusively in CTC of patients with established metastases. Patients with a CTC KRAS mutation (CTC-KRAS (mut)) had a substantially better survival, 19.4 vs. 7.4 months than patients with wild type KRAS (p = 0.015). With ScreenCell filtration, CTC are commonly found in PDAC (86 %). Molecular and genetic characterization, including mutations such as KRAS, may prove useful for prognosis. PMID- 26684804 TI - Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine. AB - Pancreatic adenocarcinoma upregulated factor (PAUF) is a new oncogene that activates signaling pathways that play a critical role in resistance to gemcitabine. We thus speculated that PAUF also plays a role in resistance to gemcitabine of pancreatic cancer cells. We established BxPC-3 cell lines with stable PAUF knockdown (BxPC-3_shPAUF) and controls (BxPC-3_shCtrl) and evaluated sensitivity to gemcitabine in vitro by MTT and flow cytometry. We established a xenograft model of human pancreatic cancer to examine PAUF function in gemcitabine resistance in vivo. Gene chip microarrays were performed to identify differentially expressed genes in BxPC-3_shPAUF and BxPC-3_shCtrl cells. Silencing PAUF increased the sensitivity of BxPC-3 cells to gemcitabine in vitro and in vivo. PAUF-knockdown BxPC-3 cell lines treated with gemcitabine showed increased proliferation inhibition and apoptosis compared with controls. Gemcitabine exhibited a more pronounced effect on reduction of BxPC-3_shPAUF tumors than BxPC-3_shCtrl tumors. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assays confirmed a significantly higher apoptotic rate of BXPC-3_shPAUF tumors compared with BXPC-3_shCtrl tumors. Gene array showed that PAUF function in gemcitabine sensitivity might involve MRP2, MRP3, MDR1, PIK3R1, and NFkB2 genes. PAUF could be considered as a key molecular target for sensitizing pancreatic cancer cells to gemcitabine. PMID- 26684805 TI - Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer. AB - Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions. PMID- 26684806 TI - Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents. AB - Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 MUm) and 4g (0.37 MUm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 MUm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series. PMID- 26684807 TI - Recurrent Amplification at 13q34 Targets at CUL4A, IRS2, and TFDP1 As an Independent Adverse Prognosticator in Intrahepatic Cholangiocarcinoma. AB - Amplification of genes at 13q34 has been reported to be associated with tumor proliferation and progression in diverse types of cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has yet to be explored. We examined two iCCA cell lines and 86 cases of intrahepatic cholangiocarcinoma to analyze copy number of three target genes, including cullin 4A (CUL4A), insulin receptor substrate 2 (IRS2), and transcription factor Dp-1 (TFDP1) at 13q34 by quantitative real-time polymerase chain reaction. The cell lines and all tumor samples were used to test the relationship between copy number (CN) alterations and protein expression by western blotting and immunohistochemical assays, respectively. IRS2 was introduced, and each target gene was silenced in cell lines. The mobility potential of cells was compared in the basal condition and after manipulation using cell migration and invasion assays. CN alterations correlated with protein expression levels. The SNU1079 cell line containing deletions of the target genes demonstrated decreased protein expression levels and significantly lower numbers of migratory and invasive cells, as opposed to the RBE cell line, which does not contain CN alterations. Overexpression of IRS2 by introducing IRS2 in SUN1079 cells increased the mobility potential. In contrast, silencing each target gene showed a trend or statistical significance toward inhibition of migratory and invasive capacities in RBE cells. In tumor samples, the amplification of each of these genes was associated with poor disease-free survival. Twelve cases (13.9%) demonstrated copy numbers > 4 for all three genes tested (CUL4A, IRS2, and TFDP1), and showed a significant difference in disease-free survival by both univariate and multivariate survival analyses (hazard ratio, 2.69; 95% confidence interval, 1.23 to 5.88; P = 0.013). Our data demonstrate that amplification of genes at 13q34 plays an oncogenic role in iCCA featuring adverse disease-free survival, which may provide new directions for targeted therapy. PMID- 26684808 TI - Arterial stiffness and impaired renal function in patients with Alzheimer's disease. AB - Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease. PMID- 26684809 TI - A Chinese case of Shapiro syndrome: responsive to carbamazepine. PMID- 26684810 TI - Is an Apicomplexan Parasite Responsible for the Collapse of the Iceland Scallop (Chlamys islandica) Stock? AB - Due to the total and unexpected collapse of the Iceland scallop, Chlamys islandica, stocks around Iceland during the 2000s, a commercial fishing ban has been imposed on this valuable resource since 2003. Following the initial identification of an apicomplexan parasite in the scallops, a long-term surveillance program was established to evaluate the effect of the parasite on the population. The infections were highly prevalent in all shell sizes throughout the study. However, the parasite only impacts mature scallops where they cause severe macroscopic changes, characterized by an extensively diminished and abnormally coloured adductor muscle. A highly significant relationship was observed between infection intensity and gonad and adductor muscle indices. The first four years of the study, were characterized by high infection intensity and very poor condition of the adductor muscle and gonads, whilst during subsequent years, infections gradually decreased and the condition of the scallops improved. Histopathological changes were restricted to the presence of apicomplexan zoites which were widely distributed, causing varying degrees of pathology in all organs. In heavy infections, muscular and connective tissues were totally necrotized, destroying significant parts of numerous organs, especially the adductor muscle, digestive gland and gonads. The progression of the disease was in good synchrony with the mortality rates and the subsequent decline observed in the scallop stock and recruitment indices. Our findings strongly suggest that the apicomplexan parasite played a major role in the collapse of the Iceland scallop stock in Breidafjordur. In addition to causing mortality, the infections significantly impact gonad development which contributes further to the collapse of the stock in the form of lower larval recruitment. Furthermore, compelling evidence exists that this apicomplexan pathogen is causing serious disease outbreaks in other scallop populations. Similar abnormal adductor muscles and the parasite itself have been identified or observed in association with other mass mortality events in several different scallop species and commercial stocks in the northern hemisphere. PMID- 26684811 TI - Targeted Therapy in Collecting Duct Carcinoma of the Kidney: A Case Report and Literature Review. PMID- 26684812 TI - Ewing Sarcoma of Urinary Bladder Showing EWSR1 Rearrangement on FISH Analysis and Unique Response to Chemotherapy. PMID- 26684813 TI - Alternative Digit Ratios and Their Relationship to Prostate Cancer. AB - BACKGROUND: The ratio of the second to the fourth digits (2D:4D) has been linked to prenatal androgen exposure and prostate cancer (PCa). The use of alternative finger ratios has been shown to be a greater indicator of sexual dimorphism when compared with the traditional 2D:4D ratio. This study aimed to assess the relationship between alternative digit ratios, racial demographics, and clinical/pathologic parameters associated with PCa. MATERIALS AND METHODS: Digital finger length measurements were made from scanned images of hands from patients with PCa. Race, age, family history, history of metastasis, and Gleason score at diagnosis were assessed in a cross-sectional clinic-based study. Demographic and clinical parameters were analyzed with respect to various alternative finger length ratios. RESULTS: Hand measurements were obtained in 354 white and 98 African-American patients with PCa. African-American men were more likely to have a smaller 2D:3D (P < .0001) and 2D:4D digit ratio (P < .0001) in both hands. Larger right (R)3D:5D (P = .0005), R4D:5D (P = .0014), and R2T:2D (P = .0501) digit ratios were present in African-Americans compared with whites. In exploratory analyses, African-American men with a smaller left (L)2T:2D ratio were younger at the time of PCa diagnosis (P = .0125). No relationship was found between the various digit ratios and Gleason score, the presence of metastatic disease, or family history. CONCLUSION: Various alternative finger length ratios show strong differences between African-American and white men in this study. The potential relationship between the 2T:2D ratio and age at diagnosis in African Americans needs additional verification. PMID- 26684814 TI - Antitumor Response to Combined Antiangiogenic and Cytotoxic Chemotherapy in Recurrent Metastatic Chromophobe Renal Cell Carcinoma: Response Signatures and Proteomic Correlates. PMID- 26684816 TI - Disseminated histoplasmosis in Central and South America, the invisible elephant: the lethal blind spot of international health organizations. PMID- 26684815 TI - Non-fatal overdoses and related risk factors among people who inject drugs in St. Petersburg, Russia and Kohtla-Jarve, Estonia. AB - BACKGROUND: This study seeks to identify the prevalence of, and risk factors associated with, non-fatal overdose among people currently injecting drugs (PWID) in St. Petersburg (Russia) and in Kohtla-Jarve (Estonia). METHODS: Five hundred eighty-eight study participants in Kohtla-Jarve (in 2012) and 811 in St. Petersburg (in 2012-2013) were recruited using respondent driven sampling for interviewing and HIV testing. RESULTS: Three-quarters (76%) of the current PWID were male. Participants from St. Petersburg were older (mean age 32.1 vs. 29.6 years, p < 0.0001) and reported a longer average duration of injecting drugs (mean duration: 13.3 vs. 10.9 years, p < 0.0001). Main drugs injected were opioids (fentanyl in Kohtla-Jarve, heroin in St Petersburg). HIV prevalence was 63% (95% CI 59-67%) in Kohtla-Jarve and 56% (95% CI 52-59%) in St. Petersburg. Two thirds of the PWID in Kohtla-Jarve and St. Petersburg reported ever having experienced a drug overdose involving loss of consciousness or stopping breathing. In Kohtla-Jarve, 28% (95% CI 24-31%) of participants and, in St Petersburg, 16% (95% CI 14-19%) of participants reported an overdose within the previous 12 months. Characteristics of injection drug use practice (longer duration of injection drug use, main drug injected), correlates of high-risk injection behaviour (higher injecting frequency, sharing), and problem alcohol use were associated with the risk of overdose within the previous 12 months. The significant factors effects did not differ between the sites. CONCLUSIONS: PWID are at high risk for overdose. Effective overdose prevention efforts at the public health scale are therefore warranted. PMID- 26684817 TI - Rates of non-confounded HIV-associated neurocognitive disorders in men initiating combination antiretroviral therapy during primary infection. AB - OBJECTIVE: To determine the prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-infected participants who initiated combination antiretroviral therapy (cART) during primary infection. DESIGN: Cross-sectional observational study. METHODS: HIV-infected men without neuropsychiatric confounds who had initiated cART during primary infection were administered a neuropsychological battery as well as questionnaires evaluating depression and quality of life. Eligibility was determined by a medical examination with history and review of records. RESULTS: Twenty-six primarily non-Hispanic white (73%), male (100%) participants were enrolled and underwent neurocognitive assessment. Mean age was 44 (28-71) years, with a median of 17 years of education (13-24). Median current and nadir CD4 T-cell counts were 828 (506-1411) and 359 (150-621) cells/MUl. All participants had plasma HIV-1 RNA less than 50 copies/ml. Median duration of cART prior to enrolment was 5.7 years (2.2-9.9). Median global deficit score was 0.17 (0.00-0.60). Only one (4%) participant was impaired. CONCLUSION: Rates of HAND in this cohort of HIV-infected men without comorbid conditions who initiated early cART are low. Our findings suggest a possible neuroprotective benefit of early cART and an important contribution of comorbidities to observed HAND prevalence. PMID- 26684818 TI - In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana. AB - OBJECTIVE: To assess associations between in-utero triple antiretrovirals (cART) versus zidovudine (ZDV) monotherapy exposure and growth among HIV-uninfected children of HIV-infected women in Botswana. DESIGN: Secondary retrospective data analysis from two randomized intervention trials of mother-to-child HIV transmission prevention. METHODS: The Mashi and Mma Bana studies enrolled HIV infected pregnant women, following their children through 24 months of age. This analysis includes singleton, full-term, HIV-exposed uninfected children. Mothers received cART or ZDV at least 2 weeks predelivery, and breastfed up to 6 months. Weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) z-scores were derived. Mean z-scores were compared by exposure group at 24 months (t-test, linear regression). RESULTS: Of 819 children, 303 were ZDV- and 516 cART-exposed in utero. Maternal median enrolment CD4 was higher among ZDV versus cART-treated mothers (393 versus 324 cells/MUl; P < 0.0001). Median duration of antepartum antiretroviral use was shorter among ZDV-treated women (5.7 versus 12.0 weeks; P < 0.0001). Median months breastfed were similar (5.9 and 6.0; P = 0.43). At 24 months, mean LAZ and WAZ were significantly lower among cART-exposed children (LAZ -1.01 versus -0.74; P = 0.003) (WAZ -0.53 versus -0.30; P = 0.002) in unadjusted analyses. Adjusting for maternal CD4, viral load, enrolment site and maternal anthropometric measures, cART-exposed children had significantly lower LAZ and WAZ at 24 months (P = 0.0004 for both). CONCLUSION: At 24 months, in utero cART-exposed children had significantly lower LAZ and WAZ. Poor growth impacts childhood and adult mortality. These findings raise concerns for potential lasting health impacts among HIV-exposed uninfected children with in utero cART exposure. PMID- 26684820 TI - Prevalence and significance of proximal renal tubular abnormalities in HIV infected patients receiving tenofovir. AB - OBJECTIVES: Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial. DESIGN AND METHODS: Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities. RESULTS: After a median of 65 months (interquartile range, 42.7-84.7), at least one tubular alteration was found in 72% of patients, mostly proteinuria (42, 50, and 14% in current, previous and never TDF use; P=0.02) and phosphaturia (46, 42, and 14%; respectively, P < 0.01). PRTD was found in 63 patients (32%) receiving TDF, ranging from 14 to 46% according to concomitant hepatitis C virus coinfection, diabetes mellitus or hypertension arterial, in contrast with six (23%) following TDF discontinuation, and zero cases in no TDF-treated patients. The use of TDF [odds ratio (OR) 13.2; 95% confidence interval (CI) 1.4-22.7; P = 0.01], cumulative time on combination antiretroviral therapy (OR 1.011; 95% CI 1.07-1.019 per month; P = 0.01), and baseline estimated glomerular filtration rate (eGFR, OR 0.97; 95% CI 0.94-0.99 per ml/min per 1.73 m higher; P = 0.04) were associated with PRTD. The number of tubular abnormalities was linearly associated with eGFR decline since TDF initiation (beta-coefficient -0.15, P = 0.02), together with age (-0.18; P = 0.01), baseline eGFR (0.49, P = 0.01), diabetes mellitus (-0.19, P = 0.02), and time on TDF (-0.23; P = 0.01). CONCLUSION: The use of TDF leads to an increased rate of tubular dysfunction, and modulated by age, baseline eGFR, and classical factors, is associated with kidney function decline. PMID- 26684819 TI - Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AB - BACKGROUND: As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent. METHODS: A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/MUl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10. The primary endpoint was at least 0.5 log10 decrease in HIV-DNA in PBMC at W56. Secondary endpoints included ultrasensitive plasma viremia, immunologic changes and safety. RESULTS: Twenty-nine patients were enrolled with median baseline 558 CD4 cell counts/MUl, 360 HIV-DNA copies/10 PBMCs and 12 years on ART. No patient in either arm achieved the primary endpoint. Addition of IL-7 induced a significant expansion of CD4 T cells, primarily central-memory cells (+5%, P = 0.001) at week 12, together with an increase in levels of HIV-DNA/10 PBMC (+0.28 log10 copies/P = 0.001), and the proportion of patients with detectable ultrasensitive plasma HIV-RNA increased compared with week 8 (P = 0.07). At weeks 56 and 80, total and memory CD4 cell counts and total HIV-DNA/ml of blood remained elevated. In contrast, HIV-DNA/million PBMC and plasma viremia returned to baseline levels whereas activated HLA-DRCD4 T cells significantly decreased. CONCLUSION: IL-7 administration and dual ART intensification induced, despite a mild HIV reactivation, an amplification of the HIV reservoir, as a result of central-memory CD4 T-cell expansion, thus limiting this IL-7 based strategy. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT01019551. PMID- 26684821 TI - HIV infection is independently associated with frailty in middle-aged HIV type 1 infected individuals compared with similar but uninfected controls. AB - BACKGROUND: Frailty is an age-related syndrome of decreased physiological reserve and resistance to stressors, associated with increased morbidity and mortality in the general elderly population. An increased prevalence of frailty has been reported amongst HIV-infected individuals. METHODS: Fried frailty phenotype was systematically assessed in predominantly virologically suppressed HIV type 1 (HIV 1)-infected and otherwise comparable HIV-uninfected participants aged at least 45 at enrollment into the AGEhIV Cohort Study. Multivariable ordinal logistic regression was used to investigate associations between HIV- and antiretroviral therapy-related covariates, markers of inflammation and body composition and prefrailty/frailty. RESULTS: Data were available for 521 HIV-infected and 513 HIV uninfected individuals. Prevalence of frailty (10.6 versus 2.7%) and prefrailty (50.7 versus 36.3%) were significantly higher in HIV-infected individuals (Ptrend < 0.001). HIV infection remained statistically significantly associated with prefrailty/frailty after adjustment for age, sex, race/ethnicity, smoking, hepatitis C infection, comorbidities and depression [adjusted odds ratio (ORadj) 2.16, P < 0.001]. A higher waist-to-hip ratio attenuated the coefficient of HIV infected status (ORadj 1.93, P < 0.001), but not waist- or hip-circumference individually or markers of inflammation. Within the HIV-infected group, parameters related to body composition were most strongly and independently associated with prefrailty/frailty: current BMI less than 20 kg/m2 (OR 2.83, P = 0.01), nadir BMI less than 20 kg/m2 (OR 2.51, P = 0.001) and waist-to-hip ratio (OR 1.79 per 0.1 higher, P < 0.001). CONCLUSION: HIV infection was independently associated with prefrailty/frailty in middle-aged HIV-infected patients compared with HIV-uninfected controls. This partly may be mediated by the higher waist- and lower hip-circumference in the HIV-infected individuals, potentially partially caused by lipodystrophy, and in part be a consequence of historic weight loss associated with advanced HIV-disease. PMID- 26684822 TI - Rilpivirine vs. efavirenz-based single-tablet regimens in treatment-naive adults: week 96 efficacy and safety from a randomized phase 3b study. AB - OBJECTIVES: To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults. DESIGN: This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial. METHODS: A total of 799 participants were randomized (1 : 1) to receive RPV/FTC/TDF or EFV/FTC/TDF. The primary efficacy endpoint evaluated proportions of participants with HIV-1 RNA less than 50 copies/ml using the Snapshot algorithm. Additional assessments included CD4 cell counts, genotypic/phenotypic resistance, adverse events, patient-reported outcomes, and quality of life questionnaires. RESULTS: At week 96, trial completion rates were 80.2% (316/394; RPV/FTC/TDF) and 74.0% (290/392; EFV/FTC/TDF). Overall, RPV/FTC/TDF was noninferior to EFV/FTC/TDF [HIV-1 RNA <50 copies/ml: 77.9 vs. 72.4%, respectively; difference -5.5; 95%CI (-0.6, 11.5); P = 0.076]. RPV/FTC/TDF was significantly more efficacious compared with EFV/FTC/TDF in participants with baseline HIV-1 RNA equal to or less than 100 000 copies/ml (78.8 vs. 71.2%; P = 0.046) and in those with CD4 cell count greater than 200 cells/MUl (80.6 vs. 73.0%; P = 0.018). There was no significant between-group difference in the CD4 cell count increase (278 +/- 189 vs. 259 +/- 191 cells/MUl; P = 0.17). Few participants developed resistance after week 48 (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). Compared with EFV/FTC/TDF, RPV/FTC/TDF was associated with fewer adverse event-related discontinuations (3.0 vs. 11.0%; P<0.001), significantly fewer adverse events due to central nervous system issues and rash, greater improvements in patient-reported symptoms, and significant improvements in the SF 12v2 quality of life questionnaire mental health composite score (P = 0.014). CONCLUSION: In treatment-naive, HIV-1-infected participants, 96-week RPV/FTC/TDF treatment demonstrated noninferior efficacy and better tolerability than EFV/FTC/TDF. PMID- 26684823 TI - Dosing antiretroviral medication when crossing time zones: a review. AB - International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID- 26684824 TI - Managing hepatitis C virus-HIV liver transplant recipients with the new direct acting antivirals: are we glimpsing a brilliant future behind our shoulders? PMID- 26684825 TI - Cracking the code: getting men tested in rural Africa. PMID- 26684826 TI - Is there a role for maraviroc to treat HIV-associated central nervous system white matter disease? PMID- 26684827 TI - Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis. AB - BACKGROUND: Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4 mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. METHOD: The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. RESULTS: We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2 induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. CONCLUSION: PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell hyperplasia induced by PGE2. PMID- 26684829 TI - IgG4-related sialadenitis: IgG4 is helpful, but biopsies are still crucial. AB - IgG4-related disease is rare, but a frequent differential diagnosis for malignant and for autoimmune diseases. Li and colleagues report the largest cohort of patients with IgG4-related sialadenitis. The observations reveal that the most important diagnostic step is obtaining biopsies. In addition, the IgG4 serum concentration may be a biomarker for the disease progression. PMID- 26684828 TI - Bilateral Strength Deficit Is Not Neural in Origin; Rather Due to Dynamometer Mechanical Configuration. AB - During maximal contractions, the sum of forces exerted by homonymous muscles unilaterally is typically higher than the sum of forces exerted by the same muscles bilaterally. However, the underlying mechanism(s) of this phenomenon, which is known as the bilateral strength deficit, remain equivocal. One potential factor that has received minimal attention is the contribution of body adjustments to bilateral and unilateral force production. The purpose of this study was to evaluate the plantar-flexors in an innovative dynamometer that permitted the influence of torque from body adjustments to be adapted. Participants were identically positioned between two setup configurations where torques generated from body adjustments were included within the net ankle torque (locked-unit) or independent of the ankle (open-unit). Twenty healthy adult males performed unilateral and bilateral maximal voluntary isometric plantar-flexion contractions using the dynamometer in the open and locked-unit mechanical configurations. While there was a significant bilateral strength deficit in the locked-unit (p = 0.01), it was not evident in the open-unit (p = 0.07). In the locked-unit, unilateral torque was greater than in the open-unit (p<0.001) and this was due to an additional torque from the body since the electromyographic activity of the agonist muscles did not differ between the two setups (p>0.05). This study revealed that the mechanical configuration of the dynamometer and then the body adjustments caused the observation of a bilateral strength deficit. PMID- 26684830 TI - A Metaphor: Religious Beliefs Exist Because Yawning Is Contagious. PMID- 26684831 TI - Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome. AB - SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug class. PMID- 26684833 TI - Characterisation of UK diets according to degree of food processing and associations with socio-demographics and obesity: cross-sectional analysis of UK National Diet and Nutrition Survey (2008-12). AB - BACKGROUND: Food processing alters food from its natural state for safety, convenience, taste or palatability. Previous research suggests that industrially processed foods, and diets high in these products, tend to be less healthful. However, most previous work is based on household, rather than individual-level, data. Little has been reported on the relationship between processed food consumption and markers of health; or on socio-demographic correlates of processed food consumption. Our objective was to describe: the nutritional content of foods classified according to degree of processing; the nutritional content of diets with different relative intakes of processed foods; the socio demographic characteristics of individuals with different relative intakes of processed foods; and the association between intake of processed foods and body weight. METHODS: Secondary analysis of data from the UK National Diet and Nutrition Survey (2008-12), a large national cross-sectional study of diet. Dietary information was collected using four-day, unweighed, food-diaries. Foods were classified as: unprocessed or minimally processed (MPF; foods with no processing or mostly physical processes applied to single whole foods), processed ingredients (PI; extracted and purified components of single whole foods), or ultra-processed food products (UPF; products produced from industrial combining of MPF and PI). RESULTS: Two thousand one hundred seventy four adults were included. MPF and diets high in these foods, had the most healthful nutritional profile. UPF did not necessarily have the least healthful nutritional profile, but diets high in these foods did. Women, and older adults consumed more energy from MPF, and less from UPF. Those living in lower occupation social class households consumed less energy from MPF, but no more from UPF. Only higher intake of PI was consistently, inversely, associated with body weight. CONCLUSIONS: This is the first study to explore correlates of processed food consumption, using individual-level data from a large, national sample. Although higher intakes of MPF and lower intakes of UPF were associated with the most healthful dietary profiles, only intake of PI was consistently associated with body weight. Consumption of UPF varied by age and gender, but, unexpectedly, not by occupational social class. Longitudinal work is required to confirm relationships with health markers. PMID- 26684835 TI - New Design for Axillary Dual-Plane Endoscopic Breast Augmentation for Asians: the Feasibility of Two Types of Dual-Plane Implant Pockets in 70 Patients as Measured by the BREAST-Q. AB - BACKGROUND: The design methods for dual-plane implant pockets for axillary endoscopic breast augmentation vary among different countries. We applied a modified approach for an Asian population. METHODS: Seventy patients with micromastia underwent our modified approach between 2011 and 2014. Breasts were divided into two types according to the soft-tissue pinch thickness of the lower pole: type I (thickness >2 cm; Group I) and type II (thickness <=2 cm; Group II). The levels at which the pectoralis major (PM) was severed were 6-6.5 cm and 3-4 cm below the nipple for type I and II pockets, respectively. Then, dissection of the retromammary space was continued from the severance level downward to the new inframammary fold for type I pockets, whereas no dissection was made for type II pockets. All patients completed the pre- and post-operative BREAST-Q augmentation modules. RESULTS: During a mean follow-up of 10 months (range, 6-12 months), patients reported higher satisfaction with breasts after surgery than before surgery (satisfaction scores of 64.9 +/- 5.6 vs. 14.7 +/- 11.0). The mean satisfaction score for the overall outcome was 91.3 +/- 17.3. However, there was no significant difference in physical well-being (87.1 +/- 10.4 vs. 85.2 +/- 11.7). No complications such as severe capsular contracture or displacement occurred. CONCLUSION: Distinguishing the need for a type I or II dual-plane pocket can lead to good outcomes and optimal soft-tissue coverage. The higher satisfaction and quality of life reported by our patients indicate that our new design is feasible and safe for most Asians with a medium build. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26684834 TI - IL-17 promoted the inhibition of medulloblastoma in mice by splenocyte injection. AB - BACKGROUND: Interleukin 17 (IL-17) is a proinflammatory cytokine produced by a new subset of activated CD4+ T cells, Th17 cells. We previously showed that increased Th17 cell populations were presented in human medulloblastoma infiltrating T cells and peripheral blood. In this study, we attempted to address the possible role of Th17 cells in the biologic activity of IL-17 for tumor control. METHODS: We grafted fresh surgically obtained medulloblastoma into syngeneic athymic nude/nude mice. We intrapertonially injected splenocyte and murine IL-17 in mice on the second day. The tumor volume and the life spans of the mice were measured. Meanwhile, the IL-17, IL-6, IL-23, Ccl2, Ccl20 and IFN gamma expression in the tumors was also examined by real-time PCR, Western blot and enzyme-linked immunosorbent assay. RESULTS: We found that medulloblastoma growth in IL-17-injected mice was significantly inhibited compared to the non-IL 17 treated mice. In contrast to the IL-17 antitumor activity observed in mice injected with splenocytes, we observed that IFN-gamma, IL-6, IL-23, Ccl2, and Ccl20 proteins were significantly increased in tumor tissues of mice injected with IL-17. CONCLUSIONS: These experiments suggest that IL-17 may promote splenocyte antitumor activity in medulloblastoma. We postulate that IL-17's antitumor activity may be related to the increased protein levels of IFN-gamma, IL-6, IL-23, Ccl2, and Ccl20. PMID- 26684836 TI - Unintentional Complications After Uneventful Rhinoplasty Operations: Case Reports and a Review of the Literature. AB - INTRODUCTION: No surgical procedure is free of complications; however, some of these complications are unintentional. Plastic surgeons may be unfamiliar with certain complications after rhinoplasty operations. In this study, we aimed to present four unintentional complications that have occurred in our patients and review the literature related to these complications. MATERIALS AND METHODS: In this study, we conducted a review of 1400 patients who were operated on from 2007 to 2015. The medical recordings of all patients were investigated. Four patients with unintentional complications after rhinoplasty operations are presented and the related literature was reviewed. CASES: Cases 1 and 2: These patients included a 26-year-old woman and a 30-year-old man who developed herpes simplex virus (HSV) infections after a primary septorhinoplasty. Case 3: This was a 25 year-old woman who developed periorbital emphysema after a primary rhinoplasty operation. Case 4: This was a 22-year-old woman who developed a second-degree burn on the nasal dorsum. All patients healed without sequel or scars. DISCUSSION: Many unexpected complications have been reported in the literature. Some of these complications include bleeding disorders, allergic reactions, dermatitis, visual loss, gastric bleeding, benign paroxysmal positional vertigo, false aneurysm after rhinoplasty, pneumocephalus, Tapia's syndrome, cavernous sinus syndrome, and skin reactions to prolene. CONCLUSION: Meticulous patient histories, consistent surgical routines, careful radiologic examinations, and frequent patient visits can help surgeons control these types of complications. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26684837 TI - Induction of Neuronal Morphology in the 661W Cone Photoreceptor Cell Line with Staurosporine. AB - PURPOSE: RGC-5 cells undergo differentiation into a neuronal phenotype with low concentrations of staurosporine. Although the RGC-5 cell line was initially thought to be of retinal ganglion cell origin, recent evidence suggests that the RGC-5 line could have been the result of contamination with 661W mouse cone photoreceptor cells. This raised the possibility that a cone photoreceptor cell line could be multipotent and could be differentiated to a neuronal phenotype. METHODS: 661W and RGC-5 cells, non-neuronal retinal astrocytes, retinal endothelial cells, retinal pericytes, M21 melanoma cells, K562 chronic myelogenous leukemia cells, and Daudi Burkitt lymphoma cells, were differentiated with staurosporine. The resulting morphology was quantitated using NeuronJ with respect to neurite counts and topology. RESULTS: Treatment with staurosporine induced similar-appearing morphological differentiation in both 661W and RGC-5 cells. The following measures were not significantly different between 661W and RGC-5 cells: number of neurites per cell, total neurite field length, number of neurite branch points, and cell viability. Neuronal-like differentiation was not observed in the other cell lines tested. CONCLUSIONS: 661W and RGC-5 cells have virtually identical and distinctive morphology when differentiated with low concentrations of staurosporine. This result demonstrates that a retinal neuronal precursor cell with cone photoreceptor lineage can be differentiated to express a neuronal morphology. PMID- 26684838 TI - Collaboration of 3D context and extracellular matrix in the development of glioma stemness in a 3D model. AB - A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor initiating cells at the apex of the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies. We observed collaboration between 3D context and laminins in promoting glioma stemness. Depending on the laminin isoform presented, U251 cells cultured on ESPS scaffolds (3D) exhibited increased expression of stemness markers compared to those cultured on tissue culture polystyrene (2D). Our results indicate the influence of 3D (versus 2D) context on integrin expression, specifically, the upregulation of the laminin-binding integrins alpha 6 and beta 4. By a colony forming assay, we showed enhanced clonogenicity of cells grown on ESPS scaffolds in collaboration with laminins 411, 421, 511 and 521. Evaluation of patient glioma databases demonstrated significant enrichment of integrin and ECM pathway networks in tumors of worse prognosis, consistent with our observations. The present results demonstrate how 3D versus 2D context profoundly affects ECM signaling, leading to stemness. PMID- 26684839 TI - Transpiration and metabolisation of TCE by willow plants - a pot experiment. AB - Willows were grown in glass cylinders filled with compost above water-saturated quartz sand, to trace the fate of TCE in water and plant biomass. The experiment was repeated once with the same plants in two consecutive years. TCE was added in nominal concentrations of 0, 144, 288, and 721 mg l(-1). Unplanted cylinders were set-up and spiked with nominal concentrations of 721 mg l(-1) TCE in the second year. Additionally, (13)C-enriched TCE solution (delta(13)C = 110.3 0/00) was used. Periodically, TCE content and metabolites were analyzed in water and plant biomass. The presence of TCE-degrading microorganisms was monitored via the measurement of the isotopic ratio of carbon ((13)C/(12)C) in TCE, and the abundance of (13)C-labeled microbial PLFAs (phospholipid fatty acids). More than 98% of TCE was lost via evapotranspiration from the planted pots within one month after adding TCE. Transpiration accounted to 94 to 78% of the total evapotranspiration loss. Almost 1% of TCE was metabolized in the shoots, whereby trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were dominant metabolites; less trichloroethanol (TCOH) and TCE accumulated in plant tissues. Microbial degradation was ruled out by delta(13)C measurements of water and PLFAs. TCE had no detected influence on plant stress status as determined by chlorophyll-fluorescence and gas exchange. PMID- 26684840 TI - Diagnostic Tools for the Modern Clinician. PMID- 26684841 TI - 2015 JCO Orthodontic Practice Study, Part 2 Practice Success. PMID- 26684842 TI - Generating an Ideal Virtual Setup with Three-Dimensional Crowns and Roots. PMID- 26684843 TI - Treatment of Labially Impacted Upper Central Incisors. PMID- 26684844 TI - Rapid Prototyping as an Adjunct for Autotransplantation of Impacted Teeth in the Esthetic Zone. PMID- 26684845 TI - A New Spring for Torque Correction. PMID- 26684846 TI - Treatment of Skeletal Class III Malocclusion with the Biofunctional System. PMID- 26684847 TI - Surgery corrects asynchrony of ribcage secondary to extra-thoracic tumor but leads to expiratory dysfunction during exercise. AB - BACKGROUND: The effect of chest wall tumours on chest wall mechanics is uncertain even less is known about the effects of resection and reconstruction. Our aim is to study how chest wall mechanics are altered in chest wall sarcoma and to determine the effect of chest wall reconstruction on chest wall kinetics. CASE PRESENTATION: Using Optoelectronic Plethysmography (OEP), total and regional chest wall volumes were measured in a patient with unilateral extra-thoracic chest wall sarcoma, before and 5 months after resection and reconstruction, during quiet breathing and exercise using cycle ergometry. During quiet breathing the unilateral tumour was associated with reduced in motion of the lower rib cage and abdominal compartments on both sides of the chest as well as asynchronous motion of the contralateral lower rib cage. Surgery corrected these abnormalities in quiet breathing. But during exercise there was a reduction in the upper rib cage motion compared to pre-operative measures from 0.43+/-0.06 to 0.36 +/- 0.02 L postoperatively (p <0.05). This impairment was characterised by a significant increase in the end expiratory volume on the operated side of the chest 5 months after surgery by 6.5 +/- 0.6 and 5.7 +/- 0.7 % during 50 and 100 % exercise respectively (p <0.0001) a finding that was not replicated in the non-operated side. CONCLUSION: This physiological study demonstrates the negative effect of chest wall tumours on global chest wall mechanics during quiet breathing and exercise and shows that surgery reverses this abnormality, but only at rest. PMID- 26684848 TI - Discrepancies between the Dermatology Life Quality Index and utility scores. AB - OBJECTIVE: In many jurisdictions, deterioration in quality of life assessed with Dermatology Life Quality Index (DLQI) is used for medical and reimbursement decisions in various dermatological conditions such as psoriasis. However, utility values for health states defined by the DLQI have not yet been evaluated. Therefore, we aim to estimate utilities for different health states described by the ten items of the DLQI. METHODS: A cross-sectional survey was performed in a convenience sample of the general population. Seven DLQI health states with total scores of 6, 11 and 16 (3-3 and 1 states, respectively) were developed. All of them were different from each other in the number of affected items and severity levels of impairment. The 10-year time trade-off method was used to value health states. RESULTS: Mean utilities elicited by the respondents (n = 308) for the three 6-, three 11- and one 16-point DLQI health states were 0.62-0.75, 0.59 0.66, and 0.56, respectively. In half of the six pairwise comparisons, where health states with the same total DLQI score were compared, significant difference between utilities was found. In eight out of the 15 comparisons between health states with different DLQI scores, utilities were not significantly different. CONCLUSIONS: Utility values for health states with identical DLQI total score may significantly vary. This result might be generalisable to various patient populations, in which the DLQI is used; nevertheless, further research is needed. The discrepancies between DLQI scores and utilities might have an impact on medical and reimbursement decisions as they make the utility gain from treatment uncertain. PMID- 26684849 TI - Regulatory effect of hydroquinone-tetraethylene glycol conjugates on zebrafish pigmentation. AB - We synthesized two hydroquinone-tetraethylene glycol conjugates (HQ-TGs) and investigated their logP, photophysical stability, and redox chemical stability. HQ-TGs are a little more hydrophilic than hydroquinone (HQ) and show an enhanced photophysical and redox chemical stability compared with HQ. In addition we studied the effect of HQ-TGs on cell viability and on zebrafish pigmentation. MTT assay in HF-16 cells showed HQ-TGs are less cytotoxic than HQ. The phenotype based image analysis of zebrafish larvae suggests that HQ-TGs suppress the pigmentation of zebrafish in a dose-dependent manner. The comparative experiments on stability, cytotoxicity, and zebrafish pigmentation between HQ and HQ-TGs suggest that mono tetraethylene glycol-functionalization of HQ is an alternative solution to overcome the adverse effect of HQ. PMID- 26684850 TI - Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes. AB - Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity. PMID- 26684852 TI - Recent advances in cancer treatment by iron chelators. AB - The development of new therapeutic alternatives for cancers is a major public health priority. Among the more promising approaches, the iron depletion strategy based on metal chelation in the tumoral environment has been particularly studied in recent decades. After a short description of the importance of iron for cancer cell proliferation, we will review the different iron chelators developed as potential chemotherapeutics. Finally, the recent efforts to vectorize the chelating agents specifically in the microtumoral environment will be discussed in detail. PMID- 26684851 TI - Preliminary investigation of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives as a novel series of mGlu5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia. AB - As part of our efforts to identify a suitable back-up compound to our recently disclosed mGlu5 positive allosteric modulator (PAM) clinical candidate VU0490551/JNJ-46778212, this letter details the investigation and challenges of a novel series of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives. From these efforts, compound 4k emerged as a potent and selective mGlu5 PAM displaying overall attractive in vitro (pharmacological and ADMET) and PK profiles combined with in vivo efficacy in preclinical models of schizophrenia. However, further advancement of the compound was precluded due to severely limiting CNS-related side-effects confirming the previously reported association between excessive mGlu5 activation and target-related toxicities. PMID- 26684854 TI - Up-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by beta Klotho. AB - BACKGROUND/AIMS: Klotho, a transmembrane protein expressed in chorioid plexus of the brain, kidney, and several other tissues, is required for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. At least in part by exerting beta-glucuronidase activity, soluble klotho regulates several ion channels and carriers. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The present study explored the effect of Klotho protein on the excitatory glutamate transporters EAAT1 (SLC1A3) and EAAT2 (SLC1A2), Na+ coupled carriers clearing excitatory amino acids from the synaptic cleft and thus participating in the regulation of neuronal excitability. METHODS: cRNA encoding EAAT1 or EAAT2 was injected into Xenopus laevis oocytes and glutamate (2 mM)-induced inward current (IGlu) taken as measure of glutamate transport. Measurements were made without or with prior 24 h treatment with soluble beta-Klotho protein (30 ng/ml) in the absence and presence of beta glucuronidase inhibitor D-saccharic acid 1,4-lactone monohydrate (DSAL,10 uM). RESULTS: IGlu was observed in EAAT1 and in EAAT2 expressing oocytes but not in water injected oocytes. In both, EAAT1 and EAAT2 expressing oocytes IGlu was significantly increased by treatment with soluble beta-Klotho protein, an effect reversed by DSAL. Treatment with beta-klotho protein increased significantly the maximal transport rate without significantly modifying the affinity of the carriers. CONCLUSION: beta-Klotho up-regulates the excitatory glutamate transporters EAAT1 and EAAT2 and thus participates in the regulation of neuronal excitation. PMID- 26684853 TI - Synthesis and cytotoxic activity of novel hexahydropyrrolo[2,3-b]indole imidazolium salts. AB - A series of novel hexahydropyrrolo[2,3-b]indole-1H-imidazolium salts were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or 2-naphthylmethyl group, were important for the cytotoxic activity. Notably, Compound 43, bearing a 2 bromobenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, was found to possess the most potent derivative against five human tumor cell lines with IC50 values below 2.68MUM and more selective towards SMMC-7721, A549 and SW480 cell lines. Compounds 25 and 39 were more selective to HL-60 and MCF-7 cell lines with IC50 values of 0.47 and 1.46MUM. PMID- 26684855 TI - Evaluation of the BinaxNOW(r) Streptococcus pneumoniae antigen test on fresh, frozen and concentrated urine samples in elderly patients with and without community-acquired pneumonia. AB - We evaluated the BinaxNOW(r) urine antigen test in elderly. For fresh un concentrated urine samples, the sensitivity for pneumococcal pneumonia was 63% and specificity 97%. After freezing and concentration, the results comparable to positive control line in intensity at 60 min gave high sensitivity (81%) with no loss in specificity (96%). PMID- 26684856 TI - A simplified method of recovering CO2 from bacterioplankton respiration for isotopic analysis. AB - A method for recovering CO2 respired by bacterioplankton for analysis of carbon isotopes was adapted for use with standard laboratory equipment without a technically demanding harvest line. The recovered CO2 was more depleted in (14)C than the dissolved organic carbon (DOC) source, which suggests a selective respiration of older carbon. PMID- 26684857 TI - Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis. AB - To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis. PMID- 26684858 TI - Knockdown of Myeloid Differentiation Factor 88 Attenuates Lipopolysaccharide Induced Inflammatory Response in Pancreatic Ductal Cells. AB - OBJECTIVES: The aim of the study was to explore the potential role of myeloid differentiation factor 88 (MyD88), which acts as an adaptor in the TLR4 signalling pathway, in immune responses of the pancreatic duct during acute pancreatitis. METHODS: Primary cultures of pancreatic duct epithelial cells from Wistar rats and cultures of the pancreatic ductal ARIP cell line were treated with lipopolysaccharide (LPS), and expression of toll-like receptor 4 mRNA was determined using real-time PCR, expression of MyD88 protein using Western blot, and levels of inflammatory cytokines using enzyme-linked immunosorbent assay. These experiments were repeated using ARIP cells in which MyD88 expression was stably knocked down. RESULTS: Toll-like receptor 4 and MyD88 expression were similar between pancreatic duct epithelial cells and ARIP cells after LPS stimulation. Myeloid differentiation factor 88 knockdown led to significantly lower levels of inflammatory cytokines after LPS induction in ARIP cells. CONCLUSIONS: Myeloid differentiation factor 88 knockdown attenuates LPS-induced inflammatory responses in pancreatic ductal cells, suggesting that the MyD88 pathway plays a critical role in their immune defense activity. PMID- 26684860 TI - Elevated Serum Pancreastatin Is an Indicator of Hepatic Metastasis in Patients With Small Bowel Neuroendocrine Tumors. AB - OBJECTIVES: Serum pancreastatin is a sensitive and specific diagnostic biomarker in neuroendocrine tumors (NETs). Elevated pancreastatin levels are associated with worse progression-free survival and overall survival in small bowel and pancreatic NETs. In this study, we investigated the clinical significance of elevated serum pancreastatin in identifying metastatic disease to the liver. METHODS: Retrospective chart review of patients with NET managed at a single institution was performed. The site of primary tumor, laboratory data, and presence of metastatic disease were reviewed. The sensitivity, specificity, and positive and negative predictive values for pancreastatin as indicator of liver metastasis were ascertained. RESULTS: Data were abstracted from 77 patient records. Small bowel was the primary tumor site in 44 patients (57%), and 49 patients had metastasis to the liver (64%). Sensitivity and specificity of serum pancreastatin was 85.7% and 66.7%, respectively, which compared with 61.5% and 43.8% for chromogranin A, in identifying liver metastasis in patients with primary tumors of the small bowel. CONCLUSIONS: Elevated serum pancreastatin is a sensitive and specific assay for detecting the incidence of liver metastasis in patients with small-bowel NET. Routine measurement of pancreastatin in patients with NET, especially in patients with small bowel primaries, is supported. PMID- 26684859 TI - Alterations in Tumor DNA Are Related to Short Postoperative Survival in Patients Resected for Pancreatic Carcinoma Aimed at Cure. AB - OBJECTIVES: Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival. METHODS: DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival. RESULTS: Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival. CONCLUSIONS: Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21. PMID- 26684861 TI - Effects of Nicotine and Vagus Nerve in Severe Acute Pancreatitis-Associated Lung Injury in Rats. AB - OBJECTIVES: The cholinergic anti-inflammatory pathway has been elucidated as a regulator of inflammatory responses in several experimental models of diseases. This regulatory mechanism is mediated by acetylcholine, released from efferent vagus nerve, interacts with alpha7 nicotinic acetylcholine receptors on immune cells. Experimental evidence indicates that vagus nerve stimulation or alpha7 nicotinic acetylcholine receptor agonists control proinflammatory cytokine production and protect animals in diverse lethal models. The aim of the study was to investigate effect of the cholinergic anti-inflammatory pathway in acute lung injury in an experimental model of severe acute pancreatitis (SAP). METHODS: In taurocholate-induced SAP in rats, pancreatitis was preceded by pretreatment with the nicotinic receptor agonist nicotine or unilateral left cervical vagotomy. RESULTS: Pretreatment with nicotine strongly alleviated severity of SAP associated lung injury through attenuating serum amylase, lipase, and interleukin 6 levels; pancreas and lung pathological injury; lung myeloperoxidase activity; lung tumor necrosis factor-alpha; and high-mobility group box 1 expression. Inversely, vagotomy pretreatment resulted in an enhanced severity of pancreatitis and lung injury. CONCLUSIONS: Our results reveal the role of the cholinergic anti inflammatory pathway in experimental SAP-associated lung injury; nicotine pretreatment exerts a protective effect and vagotomy pretreatment exerts the opposite effect. PMID- 26684862 TI - Different Hormonal Expression Patterns Between Primary Pancreatic Neuroendocrine Tumors and Metastatic Sites. AB - OBJECTIVES: Pancreatic neuroendocrine tumors (PNETs) are known to have heterogeneity in terms of their ability to produce multiple hormones. The aim of this study was to evaluate the heterogeneity of PNETs from the viewpoint of hormonal expression. METHODS: The expressions of 4 representative hormones, gastrin, insulin, glucagon, and somatostatin, in both primary and metastatic lesions, were analyzed by immunohistochemical staining in 20 patients with metastatic PNETs (6 gastrinomas, 1 insulinoma, 1 glucagonoma, and 12 nonfunctioning PNETs [NF-PNETs]). Metastatic sites included lymph nodes in all 20 patients and liver metastasis in 7 patients (2 gastrinomas and 5 NF-PNETs). RESULTS: There were 6 PNETs with multiple hormone secretion (30%), and positive expression of 1 or more hormones was found in 9 of 12 patients whose primary tumors were diagnosed as NF-PNETs. The positive concordance rate of the hormonal expression pattern between primary tumors and metastatic lymph nodes and between primary tumors and hepatic metastasis were 50% and 11%, respectively. Three patients had metastatic lesions with positive hormonal expression, whereas their primary tumors were negative. CONCLUSIONS: Hormonal expressions are often different between the primary tumors and metastatic sites of PNETs. PMID- 26684863 TI - Widespread lytic lesions-A metastatic or vasculitic process? AB - INTRODUCTION: This case highlights the complexities in the initial diagnosis and investigations of widespread lytic lesions initially perceived to be a widespread metastatic process and the consideration of alternative diagnosis. PRESENTATION OF CASE: A 57 year-old man with a background of psoriatic arthritis presented to the rheumatology department with lumbar back pain and sensory disturbance over L4/5. Magnetic resonance imaging (MRI) and bone scan identified lesions consistent with bony metastases at L5. The patient previously had a raised prostate specific antigen (PSA) of 10.8MUg/L (normal<4) but prostate biopsy was benign. Multiple metastatic deposits in the liver and kidneys (confirmed necrotic tissue on biopsy) were identified through further investigations. The initial diagnosis of malignancy was challenged after a positron emission tomography (PET) scan showed lesions highly suggestive of polyarteritis nodosa (PAN) and subsequent magnetic resonance angiogram (MRA) revealed stenosis and aneurysm in the renal artery in keeping with PAN. Therefore what was initially thought to be a widespread metastatic disease process was in fact the manifestation of a systemic vasculitic disease. DISCUSSION: PAN is a vasculitis that predominantly involves small to medium-sized vessels. The disease can affect any site in the body, but holds a predisposition for organs such as kidneys, heart and the gastrointestinal tract. Differential diagnosis of PAN should be considered in patients with widespread lytic lesions. CONCLUSION: Due to the pathological nature of PAN and its variable clinical manifestations that add to the challenges of its diagnosis, one must hold a high clinical suspicion, even in urological conditions. PMID- 26684864 TI - Xantogranulomatous pyelonephritis: The missed diagnosis. AB - INTRODUCTION: Xantogranulomatous pyelonephritis (XGPN) is a rare chronic inflammatory disease of the kidney that can be focal or diffuse with the focal form imitating greatly renal cell carcinoma (RCC). PRESENTATION OF CASE: We report a challenging clinical case of a 38-year old male with right flank pain persisting for 3-months, imaging showed an 8cm heterogenous mass of the upper pole of the right kidney and invading the liver. A right radical nephrectomy including the adrenal in the resection was performed under the tentative diagnosis of renal cell carcinoma (RCC) whereas histology revealed focal XGPN. DISCUSSION: Preoperative diagnosis of focal XGPN was difficult because of radiological similarities to RCC and lack of history of stone disease or urinary tract infection. CONCLUSION: This case highlights the need to include XGPN in the differential diagnosis of RCC even in the era of modern imaging. PMID- 26684865 TI - Adrenohepatic fusion: Adhesion or invasion in primary virilizant giant adrenal carcinoma? Implications for surgical resection. Two case report and review of the literature. AB - INTRODUCTION: Adrenohepatic fusion means union between the adrenal gland and the liver, intermingling its parenchymas. It is not possible to identify this condition by image tests. Its presence implies radical and multidisciplinar approach. PRESENTATION OF CASES: We report two female cases of 45 and 50 years old with clinical virilization and palpable mass on the abdominal right upper quadrant corresponding to adrenocortical carcinoma with hepatic fusion. The contrast-enhanced tomography showed an indistinguishable mass involving the liver and the right adrenal gland. In the first case, the patient had a two-time operation, the former removing only the adrenal carcinoma, and the second performing a radical surgery after an early relapse. In the second case, a radical right en bloc adrenohepatectomy was performed. Both cases were pathologically reported as liver-infiltrating adrenal carcinoma. Only in the second case the surgery was radical effective as first intention to treat, with 3 years of disease-free survival. DISCUSSION: ACC is a rare entity with poor prognosis. The major indicators of malignancy are tumour diameter over 6cm, local invasion or metastasis, secretion of corticosteroids, virilization and hypertension and hypokalaemia. The parenchymal fusion of the adrenal cortical layer can be misdiagnosed as hepatocellular carcinoma with adhesion with the Glisson capsule. AHF in such cases may be misinterpreted during surgery, what may impair its resectability, and therefore the survival. The surgical treatment must be performed en bloc, often using liver vascular control. Postoperative treatment must be offered immediately after surgery. CONCLUSION: We report two consecutive rare cases of adrenohepatic fusion in giant right adrenocortical carcinoma, not detectable by imaging, what has important implications for the surgical decision making. As radical surgery is the best choice to offer a curative treatment, it has to be performed by a multidisciplinary well-assembled team, counting with endocrine and liver surgeons, and transplant surgeons in case of vena cava involvement, in order to maximize the disease-free survival. PMID- 26684866 TI - Impact of Porosity and Electrolyte Composition on the Surface Charge of Hydroxyapatite Biomaterials. AB - The success or failure of a material when implanted in the body is greatly determined by the surface properties of the material and the host tissue reactions. The very first event that takes place after implantation is the interaction of soluble ions, molecules and proteins from the biological environment with the material surface leading to the formation of an adsorbed protein layer that will later influence cell attachment. In this context, the particular topography and surface charge of a material become critical as they influence the nature of the proteins that will adsorb. However, very limited information is available on the surface charge of porous substrates. Only until very recently was the determination of the zeta potential on porous membranes accurately determined. The goal of this work was to implement the previous findings for the determination of the zeta potential of a series of porous hydroxyapatite (HA) substrates and to assess how porosity affects the measurements. In addition, studies using various electrolytes were also performed to prove how the specific affinity of certain ions for HA can further impact surface charge. The results showed that all materials exhibited very similar external surface charge (approximately -23 mV), consistent with their almost identical topographies. However, the presence of interconnected pores underneath the sample surface resulted in an additional internal zeta potential that varied with the porosity content. Measurements with different electrolytes confirmed the selectivity of divalent ions for HA underlying the importance of testing biomaterials using relevant electrolytes. PMID- 26684867 TI - The overexpression of Thioredoxin-1 suppressing inflammation induced by methamphetamine in spleen. AB - BACKGROUND: Methamphetamine (METH) is an addictive psychostimulant and has been shown to induce oxidative stress and inflammation in various tissues. Thioredoxin 1 (Trx-1) plays the roles in regulating redox and inhibiting inflammation. Whether Trx-1 is involved in METH-induced inflammation is still unknown. METHODS: The present study was designed to investigate inflammatory factors in spleen of wild type and Trx-1 overexpression transgenic mice after METH treatment. RESULTS: We found the mRNA level of Trx-1 was decreased and mRNA level of Trx-1 binding protein-2 (TBP-2) was increased. The mRNA levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma(IFN-gamma), interleukin-2 (IL-2), T-bet and signal transducer and activators of transcription 4 (STAT 4) were increased and the mRNA levels of IL-10, GA-TA-binding protein-3 (GATA-3) and STAT 6 were decreased. Overexpression of Trx-1 reversed the above effects induced by METH. CONCLUSION: The present study showed for the first time that Trx-1 overexpression suppressed the inflammation induced by METH. PMID- 26684868 TI - Visual and verbal learning deficits in Veterans with alcohol and substance use disorders. AB - BACKGROUND: This study examined visual and verbal learning in the early phase of recovery for 48 Veterans with alcohol use (AUD) and substance use disorders (SUD, primarily cocaine and opiate abusers). Previous studies have demonstrated visual and verbal learning deficits in AUD, however little is known about the differences between AUD and SUD on these domains. Since the DSM-5 specifically identifies problems with learning in AUD and not in SUD, and problems with visual and verbal learning have been more prevalent in the literature for AUD than SUD, we predicted that people with AUD would be more impaired on measures of visual and verbal learning than people with SUD. METHODS: Participants were enrolled in a comprehensive rehabilitation program and were assessed within the first 5 weeks of abstinence. Verbal learning was measured using the Hopkins Verbal Learning Test (HVLT) and visual learning was assessed using the Brief Visuospatial Memory Test (BVMT). RESULTS: Results indicated significantly greater decline in verbal learning on the HVLT across the three learning trials for AUD participants but not for SUD participants (F=4.653, df=48, p=0.036). Visual learning was less impaired than verbal learning across learning trials for both diagnostic groups (F=0.197, df=48, p=0.674); there was no significant difference between groups on visual learning (F=0.401, df=14, p=0.538). DISCUSSION: Older Veterans in the early phase of recovery from AUD may have difficulty learning new verbal information. Deficits in verbal learning may reduce the effectiveness of verbally based interventions such as psycho-education. PMID- 26684869 TI - Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-alpha and IL-1beta, and Activation of the NF-kappaB Signaling Pathway. AB - Testes-specific protease 50 (TSP50) is abnormally overexpressed in many kinds of cancers and promotes cell proliferation and migration. However, whether TSP50 can influence the tumor microenvironment, especially the function of immune cells in the microenvironment, remains largely unknown. We demonstrated that exposure to the conditioned medium from TSP50-overexpressing cells, or co-culture with TSP50 overexpressing cells, enhanced the cytokine production and phagocytic activities of macrophages, and induced M2b polarization. Further investigation showed that production of TNF-alpha and IL-1beta was strongly induced by TSP50 in TSP50 overexpressing cells. TSP50-induced TNF-alpha and IL-1beta were main factors that mediated the effects of TSP50-overexpressing cells on macrophages. The NF-kappaB pathway could be activated in macrophages upon the treatment of conditioned medium of TSP50-overexpressing cells and its activation is necessary for the observed effects on macrophages. Taken together, our results suggested that oncogenic TSP50 expressed in cells could activate surrounding macrophages and induce M2b polarization, partly through inducing TNF-alpha/ IL-1beta secretion and subsequent NF-kappaB pathway activation. This implies a potential mechanism by which oncogene TSP50 regulates tumor microenvironment to support tumor development. PMID- 26684870 TI - Neuro-Immunotherapies: A 30-year Retrospective of an Overwhelming Success and a Brighter Future. PMID- 26684871 TI - Inflammatory but not apoptotic death of granulocytes citrullinates fibrinogen. AB - BACKGROUND: Neutrophil activation induces citrullination of intracellular targets of anticitrullinated peptide antibodies (ACPA), which are specific for rheumatoid arthritis (RA). Citrullinated fibrinogen is bound by ACPA but it is less well understood how extracellular proteins are citrullinated. The cells that produce fibrinogen, hepatocytes, do not express peptidyl arginine deiminase (PAD) enzymes nor do PAD enzymes include N-terminal signal peptides to direct them into the secretory pathway. We hypothesized that dying neutrophils release PAD in the extracellular space, and that this could cause citrullination of target extracellular antigens relevant to RA such as fibrinogen. METHODS: HL60 cells were differentiated into neutrophil-like cells by treatment with all-trans retinoic acid (ATRA). Differentiation was confirmed by CD11b staining, PAD4, PAD2 and myeloperoxidase expression, cell division, and nuclear morphology. Death was induced with various stimuli, including freeze-thaw to induce necrosis, Ionomycin and PMA to induce NETosis, and UV-B to induce apoptosis. Death markers were assessed by immunohistochemistry and flow cytometry. To quantify extracellular citrullination, dying ATRA-differentiated HL60 cells were cultured with fibrinogen for 24 hours and supernatants were probed for fibrinogen citrullination, PAD2 and PAD4 by western blot. RESULTS: While both NETotic and necrotic ATRA differentiated HL60 cells citrullinated fibrinogen, apoptotic cells did not citrullinate fibrinogen, even when allowed to undergo secondary necrosis. Incubation of necrotic neutrophil lysates with fibrinogen also causes fibrinogen citrullination. PAD2 and PAD4 were detected by western blot of supernatants of ATRA-differentiated HL60 cells undergoing necrotic and NETotic death, but not apoptotic or secondarily necrotic cell death. CONCLUSION: We implicate granulocytes undergoing inflammatory cell death as a mechanism for altering extracellular self-proteins that may be targets of autoimmunity linked to inflammatory diseases such as rheumatoid arthritis. PMID- 26684873 TI - Aging Is No Longer a "First-World Problem". PMID- 26684872 TI - Economic Evaluation of a General Hospital Unit for Older People with Delirium and Dementia (TEAM Randomised Controlled Trial). AB - BACKGROUND: One in three hospital acute medical admissions is of an older person with cognitive impairment. Their outcomes are poor and the quality of their care in hospital has been criticised. A specialist unit to care for older people with delirium and dementia (the Medical and Mental Health Unit, MMHU) was developed and then tested in a randomised controlled trial where it delivered significantly higher quality of, and satisfaction with, care, but no significant benefits in terms of health status outcomes at three months. OBJECTIVE: To examine the cost effectiveness of the MMHU for older people with delirium and dementia in general hospitals, compared with standard care. METHODS: Six hundred participants aged over 65 admitted for acute medical care, identified on admission as cognitively impaired, were randomised to the MMHU or to standard care on acute geriatric or general medical wards. Cost per quality adjusted life year (QALY) gained, at 3 month follow-up, was assessed in trial-based economic evaluation (599/600 participants, intervention: 309). Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data (55%). RESULTS: The total adjusted health and social care costs, including direct costs of the intervention, at 3 months was L7714 and L7862 for MMHU and standard care groups, respectively (difference -L149 (95% confidence interval [CI]: -298, 4)). The difference in QALYs gained was 0.001 (95% CI: -0.006, 0.008). The probability that the intervention was dominant was 58%, and the probability that it was cost saving with QALY loss was 39%. At L20,000/QALY threshold, the probability of cost effectiveness was 94%, falling to 59% when cost-saving QALY loss cases were excluded. CONCLUSIONS: The MMHU was strongly cost-effective using usual criteria, although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded. Nevertheless, this model of care is worthy of further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136148. PMID- 26684874 TI - Cytomegalovirus retinitis. PMID- 26684875 TI - Primary aorto-enteric fistula: a diagnosis not to be missed. PMID- 26684876 TI - Psychiatric Status across Body Mass Index in a Mediterranean Spanish Population. AB - BACKGROUND: Mental and body weight disorders are among the major global health challenges, and their comorbidity may play an important role in treatment and prevention of both pathologies. A growing number of studies have examined the relationship between psychiatric status and body weight, but our knowledge is still limited. OBJECTIVE: The present study aims to investigate the cross sectional relationships of psychiatric status and body mass index (BMI) in Malaga, a Mediterranean city in the South of Spain. MATERIALS AND METHODS: A total of 563 participants were recruited from those who came to his primary care physician, using a systematic random sampling, non-proportional stratified by BMI categories. Structured clinical interviews were used to assess current Axes-I and II mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). BMI was calculated as weight (Kg) divided by square of height in meters (m2). Logistic regression was used to investigate the association between BMI and the presence of any mental disorder. BMI was introduced in the models using restricted cubic splines. RESULTS: We found that high BMI values were directly associated with mood and adjustment disorders, and low BMI values were directly associated with avoidant and dependent personality disorders (PDs). We observed an inverse relationship between low BMI values and cluster A PDs. There were not significant relationships between anxiety or substance-related disorders and BMI. CONCLUSION: Psychiatric status and BMI are related in a Mediterranean Spanish population. A multidisciplinary approach to both pathologies becomes increasingly more necessary. PMID- 26684877 TI - Relative frequency of non-Hodgkin lymphoma subtypes in selected centres in North Africa, the middle east and India: a review of 971 cases. AB - Comparative data regarding the distribution of non-Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly-diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91.7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male-to-female ratio was significantly higher in NAF/ME/IN (1.8) compared to NA (1.1; P< 0.05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B-NHL (28.4%) and a higher proportion of HG B-NHL (58.4%) were found compared to NA (56.1% and 34.3%, respectively). Diffuse large B-cell lymphoma was more common in NAF/ME/IN (49.4%) compared to NA (29.3%), whereas follicular lymphoma was less common in NAF/ME/IN (12.4%) than in NA (33.6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences. PMID- 26684878 TI - Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein. AB - BACKGROUND: Human CD4+ T cell responses to important animal allergens are still insufficiently understood. OBJECTIVE: To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. METHODS: Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen. RESULTS: Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy. PMID- 26684879 TI - Dynamic weight bearing as a non-reflexive method for the measurement of abdominal pain in mice. AB - BACKGROUND: Chronic pelvic pain (CPP) is a high burden for patients and society. It affects 15-24% of women in reproductive age and is an area of high unmet medical need. CPP can be caused by a wide range of visceral diseases such as abdominal infections, gastrointestinal or gynaecological diseases like endometriosis. Despite the high medical need for this condition, pharmacological approaches are hampered by the limited number of available methods for the behavioural evaluation of pain in inflammation-driven animal models of pelvic pain. METHODS: The dynamic weight bearing (DWB) system was used for the evaluation of spontaneous behaviour changes in the zymosan-induced peritonitis mouse model. Inflammatory mediator levels were evaluated in peritoneal lavage and their correlation with the behavioural endpoints was assessed. We evaluated the effect on behavioural endpoints of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib and the Nav 1.8 blocker A-803467. RESULTS: The presence of a relief posture, characterized by a significantly increased weight distribution towards the front paws, was observed following intraperitoneal injection of zymosan. A positive correlation was detected between PGE2 levels in the peritoneal lavage and DWB endpoints. In addition, zymosan-induced weight bearing changes were reverted by celecoxib and A-803467. CONCLUSIONS: This study described for the first time the use of DWB as a non-subjective and non-reflexive method for the evaluation of inflammatory-driven abdominal pain in a mouse model. PMID- 26684880 TI - Implicit cognition about self-injury predicts actual self-injurious behavior: results from a longitudinal study of adolescents. AB - BACKGROUND: The implicit association hypothesis of nonsuicidal self-injury (NSSI) proposes that individuals who engage in self-injury develop, over time, strong associations between themselves and NSSI, and their identification with this behavior guides their future selection of NSSI to cope. Prior research has established a relationship between implicit NSSI associations (using an Implicit Association Test for Self-Injury) and engagement in NSSI. However, previous studies have been small and cross-sectional, and thus underpowered to examine the nature of this association and the extent to which implicit associations predict the persistence of NSSI. METHODS: This study builds on previous research in a prospective, longitudinal examination of implicit self-identification with NSSI in a large sample of middle school students. NSSI behavior and implicit NSSI associations were assessed annually in school at three time points. RESULTS: Adolescents who engaged in NSSI exhibited stronger implicit self-identification with NSSI than adolescents who did not engage in NSSI. Moreover, implicit NSSI identification was stronger among adolescents who engaged in cutting, frequent NSSI, and recent NSSI. A reciprocal association was observed between NSSI frequency and implicit NSSI identification over 1 year. Notably, implicit NSSI identification uniquely and prospectively predicted engagement in NSSI over the subsequent year. CONCLUSIONS: Implicit self-identification with NSSI may track both trait- and state-related changes in the behavior and, importantly, may help predict continued engagement in NSSI. PMID- 26684881 TI - Timberol(r) Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans. AB - In mice, trace amine-associated receptors (TAARs) are interspersed in the olfactory epithelium and constitute a chemosensory subsystem that is highly specific for detecting volatile amines. Humans possess six putative functional TAAR genes. Human TAAR5 (hTAAR5) is highly expressed in the olfactory mucosa and was shown to be specifically activated by trimethylamine. In this study, we were challenged to uncover an effective blocker substance for trimethylamine-induced hTAAR5 activation. To monitor blocking effects, we recombinantly expressed hTAAR5 and employed a commonly used Cre-luciferase reporter gene assay. Among all tested potential blocker substances, Timberol(r), an amber-woody fragrance, is able to inhibit the trimethylamine-induced hTAAR5 activation up to 96%. Moreover, human psychophysical data showed that the presence of Timberol(r) increases the olfactory detection threshold for the characteristic fishy odor of trimethylamine by almost one order of magnitude. In conclusion, our results show that among tested receptors Timberol(r) is a specific and potent antagonist for the hTAAR5 mediated response to trimethylamine in a heterologous system. Furthermore, our data concerning the observed shift of the olfactory detection threshold in vivo implicate that hTAAR5 or other receptors that may be inhibited by Timberol(r) could be involved in the high affinity olfactory perception of trimethylamine in humans. PMID- 26684882 TI - Evaluation of a new bio-impedance spectroscopy device in healthy Japanese. AB - BACKGROUND: The use of a new bio-impedance spectroscopy device (Body Composition Monitor, BCM) in the field of dialysis became possible in Japan. However, it is unknown whether the data obtained using this apparatus are indicative for Japanese dialysis patients. OBJECTIVE: To compare individual fluid status in healthy Japanese using the BCM device with the data obtained from healthy Caucasians. METHODS: A total of 219 volunteers (female vs. male, 150 vs. 69; mean age, 68.8 +/- 8.4 years; mean BMI, 22.6 +/- 2.9 kg/m2) were enrolled. The measurement was performed by the end of the morning before exercise. RESULTS: Mean over-hydration (OH) level was 0.7 +/- 0.8 L. Nearly 80% of subjects had values equivalent to the standard values of healthy Caucasians (-1.1~1.1 L). Age had a weak positive correlation to OH. The fat tissue index levels were slightly lower in Japanese than in Caucasians. On the other hand, the levels of lean tissue index and ECW/ICW (E/I) ratio did not differ between Japanese and Caucasians. E/I ratio showed a good correlation with OH level. CONCLUSION: Fluid status of healthy Japanese was equivalent to the standard value of Caucasians. Although validity of using parameters from healthy Caucasians in healthy Japanese population was considered to be confirmed, validity of use in Japanese dialysis patients should be evaluated further using the parameters from healthy Caucasians. PMID- 26684883 TI - Influence of viscoelastic properties of an hyaluronic acid-based hydrogel on viability of mesenchymal stem cells. AB - BACKGROUND: The present research is involved in the framework of the biotherapy using mesenchymal stem cells (MSCs). Here, MSC encapsulation in a hydrogel based on hyaluronic acid (HA) is investigated to optimize the composition of the biomaterial. METHODS: Several formulations candidates of the hydrogel (9 in total) are postulated as a scaffold for the 3D MSC culture in order to investigate their potential to mimic the in vivo cellular environment. Rheological measurements in oscillation mode of complex modulus and complex viscosity are performed on the different hydrogels. Biological tests are carried out for the measurement of the cell viability of MSC encapsulated in the hydrogels. RESULTS: Rheological and biological findings are correlated together in order to establish relationships between the viscoelastic properties of the hydrogel and the cellular viability of MSC. CONCLUSIONS: In the light of the viability results, the composition of the hydrogel was related to the MSC proliferation. Thus, such relations are useful tools for scientists offering them more flexibility in the design of their hydrogels while ensuring an acceptable level of MSC viability. PMID- 26684884 TI - High sensitivity, high surface area Enzyme-linked Immunosorbent Assay (ELISA). AB - BACKGROUND: Enzyme-linked immunosorbent assays (ELISA) are considered the gold standard in the demonstration of various immunological reactions with an application in the detection of infectious diseases such as during outbreaks or in patient care. OBJECTIVE: This study aimed to produce an ELISA-based diagnostic with an increased sensitivity of detection compared to the standard 96-well method in the immunologic diagnosis of infectious diseases. METHODS: A '3DStack' was developed using readily available, low cost fabrication technologies namely nanoimprinting and press stamping with an increased surface area of 4 to 6 times more compared to 96-well plates. This was achieved by stacking multiple nanoimprinted polymer sheets. The flow of analytes between the sheets was enhanced by rotating the 3DStack and confirmed by Finite-Element (FE) simulation. An Immunoglobulin G (IgG) ELISA for the detection of antibodies in human serum raised against Rubella virus was performed for validation. RESULTS: An improved sensitivity of up to 1.9 folds higher was observed using the 3DStack compared to the standard method. CONCLUSIONS: The increased surface area of the 3DStack developed using nanoimprinting and press stamping technologies, and the flow pattern between sheets generated by rotating the 3DStack were potential contributors to a more sensitive ELISA-based diagnostic device. PMID- 26684885 TI - A case study on medical image enhancement based on II curvelet. AB - A method is presented in this paper for medical image enhancement based on II curvelet. After the wavelet decomposition of medical image, we continue to break down the high-frequency sub-images, in order to get more detailed information. We have also designed the corresponding gain weight function for the edge enhancement of low-frequency sub-images, using II curvelet to extract the edge information, which has advantages over the normal curvelet transform. This method has overcome the disadvantages of the present medical image enhancement algorithm based on wavelet theory, for instance, (1) most of the present methods only decompose the low-frequency sub-images to get detailed information; (2) they can not well extract the tumors or other large areas of edge information of medical images. In simulation experiments, we enhanced the mammography X-ray images of breast provided by Heilongjiang Provincial Tumor Hospital, and compared our algorithm with several traditional image enhancement methods. The results shows that with our enhancement algorithm based on II curvelet, the textures and edges of the image can be reflected clearly, and the calcifications in the image are independent, at the same time, this method has the superiority when enhancing the images which have been added noise to. PMID- 26684886 TI - Influence of the crystallinity of a sputtered hydroxyapatite film on its osteocompatibility. AB - Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency sputtering, and the sputtered films were crystallized using a hydrothermal treatment at 120 degrees C and 170 degrees C to evaluate the influence of the crystallinity of the HA film on its osteocompatibility. The crystallite size and surface morphology of the films were observed using X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The alkaline phosphatase (ALP) expression, osteocalin (OCN) expression and bone formation of osteoblast cells on the films were measured to evaluate the osteocompatibility of the film.The crystallite size increased as the hydrothermal temperature increased, and the crystallite sizes of the film treated at 120 degrees C and 170 degrees C were 82.2+/-12.3 nm and 124.7+/-13.3 nm, respectively. Globular particles were observed in the hydrothermally treated film using SEM. The size of the particles on the film increased as the hydrothermal temperature increased, and the width of the particles on the film treated at 120 degrees C and 170 degrees C were approximately 120-190 nm and 300-500 nm, respectively. In the osteoblast cell culture experiments, the ALP expression, OCN expression and bone formation area on the films treated at 120 degrees C were higher than those treated for films treated at 170 degrees C. PMID- 26684887 TI - Measuring the adherence energy of the resin-metal interface with two fracture mechanics methods: The DCB and NTP tests. AB - OBJECTIVE: To evaluate the abilities of the DCB and the NTP test for measuring adherence of an adhesive joint between a resin and a metal interface. METHODS: Two-hundred stainless steel metal beams (diam. 50*5*2 mm) were cast and treated by the following methods: (1) sandblasting with aluminum oxide, followed by treatment with (2) the Rocatec system or (3) the Alloy primer. Superbond and Panavia F 2.0 were used as adhesives. The fracture energy (G1C) and fracture toughness (K1C) of two adhesives were compared by two-way analysis of variance. RESULTS: With the DCB test, Superbond was more effective than Panavia, regardless of the surface treatment and conditions of crack propagation. The overall effectiveness of the treatments was in the following order: sandblasting + Rocatec > sandblasting alone > sandblasting + Alloy primer. The adherence energy in an aqueous medium was lower than that in air. With the NTP test, similar performances were obtained with three surface treatments. However, the potential of Rocatec seemed slightly higher. CONCLUSIONS: The DCB and NTP tests provide independent measures of the inherent value of an adhesive. Rocatec appeared to provide greater resistance of the bonded joints in an aqueous environment. PMID- 26684888 TI - Single-trial EEG analysis using similarity measure. AB - Single-trial electroencephalogram (EEG) data are analyzed with similarity measure. Time-frequency representation is constructed from EEG signals. It is then weighted with t-statistics. Finally, the test data are discriminated with similarity measure. Compared with non-weighted version, the experimental results indicate that the proposed method obtains better results in classification accuracy. PMID- 26684889 TI - 3D cell culture to determine in vitro biocompatibility of bioactive glass in association with chitosan. AB - This study reports the in vitro biocompatibility of a composite biomaterial composed of 46S6 bioactive glass in association with chitosan (CH) by using 3D osteoblast culture of SaOS2. The 46S6 and CH composite (46S6-CH) forms small hydroxyapatite crystals on its surface after only three days immersion in the simulated body fluid. For 2D osteoblast culture, a significant increase in cell proliferation was observed after three days of contact with 46S6 or 46S6-CH immersed media. After six days, 46S6-CH led to a significant increase in cell proliferation (128%) compared with pure 46S6 (113%) and pure CH (122%). For 3D osteoblast culture, after six days of culture, there was an increase in gene expression of markers of the early osteoblastic differentiation (RUNX2, ALP, COL1A1). Geometric structures corresponding to small apatite clusters were observed by SEM on the surface of the spheroids cultivated with 46S6 or 46S6-CH immersed media. We showed different cellular responses depending on the 2D and 3D cell culture model. The induction of osteoblast differentiation in the 3D cell culture explained the differences of cell proliferation in contact with 46S6, CH or 46S6-CH-immersed media. This study confirmed that the 3D cell culture model is a very promising tool for in vitro biological evaluation of bone substitutes' properties. PMID- 26684890 TI - Sterilization of auto-crosslinked hyaluronic acid scaffolds structured in microparticles and sponges. AB - This work evaluated the effects of UV irradiation, plasma radiation, steam and 70% ethanol treatments on the sterilization and integrity of auto-crosslinked hyaluronic acid (HA-ACP) scaffolds structured in microparticles and sponges aiming in vivo applications for regenerative medicine of bone tissue. The integrity of the microparticles was characterized by rheological behavior, while for the sponges, it was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. The effectiveness of the sterilization treatment was verified by the number of microorganism colonies in the samples after the treatments. In conclusion, plasma radiation was the best treatment for the sponges, while steam sterilization in the autoclave at 126 degrees C (1.5 kgf/cm2) for 5 min was the best treatment for the microparticles. PMID- 26684891 TI - Finite element analyses of femoroacetabular impingement before and after hip arthroscopy. AB - In this study, three-dimensional finite element models based on the specific anatomy of a patient presenting a femoroacetabular impingement of the "cam" type were developed. The finite element meshes were obtained from arthrographic magnetic resonance images captured before and after hip arthroscopy. All soft tissues were considered linear elastic and isotropic and the bones were assumed as rigid. Physiological loads and rotational motions were applied. Stresses and contact pressures were evaluated in these patient specific models in order to better interpret the mechanism of aggression of the cartilages and of the labrum and to evaluate the effectiveness of the surgery. The results of the analyses are presented and discussed. The values obtained for the stresses and contact pressures in the pathological hip were similar to those reported by other models based on idealised geometries or similar reconstruction methodologies and were larger than the ones obtained in the same hip after the surgical treatment. The surgical treatment effectively reduces the intra-articular pressures and stresses approaching the values of a normal hip. Thus, early surgical treatment may help to prevent, or delay, the joint degeneration. PMID- 26684895 TI - Interest in nursing among academic degree holders in Israel: A cross-sectional quantitative study. AB - BACKGROUND: The shortage of nurses is a global problem. One strategy for producing more registered nurses worldwide and in Israel in particular is to offer graduate entry nursing programs for individuals with non-nursing academic degrees. In order to recruit academic degree holders into the nursing profession, it is important to identify factors that might attract them. OBJECTIVES: The purpose of this study was to explore whether the perception of nurse characteristics by academic degree holders is associated with their interest in enrolling in a graduate entry nursing program or in recommending this program to a family member, and whether ethnic background, gender and interaction with a nurse have an effect on this interest. DESIGN: A cross-sectional quantitative study. SETTINGS: The setting of the study was on the campus of Tel Aviv University. PARTICIPANTS: A convenience sample of 522 individuals with an academic education, men and women, aged 18-60 and equally distributed between Jewish and Arab Israelis, took part in the study. METHODS: Participants completed a questionnaire based on the Porter Nursing Image Scale. RESULTS: A moderate positive correlation was found between perception of nurses and interest in nursing (r=0.32, p<0.01). Arab Israelis, women, and individuals who have or have had interactions with nurses, viewed nurses in a more positive light and had a higher interest in nursing than their counterparts. CONCLUSIONS: Efforts should be made to foster a positive public image of nursing among the population of people with an academic education. Recruitment strategies should be tailored to each of this population's subgroups. PMID- 26684896 TI - Clinical leadership as an integral curriculum thread in pre-registration nursing programmes. AB - BACKGROUND: In recent years there has been a growth in leadership development frameworks in health for the existing workforce. There has also been a related abundance of leadership programmes developed specifically for qualified nurses. There is a groundswell of opinion that clinical leadership preparation needs to extend to preparatory programmes leading to registration as a nurse. To this end a doctoral research study has been completed that focused specifically on the identification and verification of the antecedents of clinical leadership (leadership and management) so they can shape the curriculum content and the best way to deliver the curriculum content as a curriculum thread. OBJECTIVES: To conceptualise how the curriculum content, identified and verified empirically, can be structured within a curriculum thread and to contribute to the discussion on effective pedagogical approaches and educational strategies for learning and teaching of clinical leadership. DESIGN: A multi-method design was utilised in the research in Australia. Drawing on core principles in critical social theory, an integral curriculum thread is proposed for pre-registration nursing programmes that identifies the antecedents of clinical leadership; the core concepts, together with the continuum of enlightenment, empowerment, and emancipation. CONCLUSIONS: The curriculum content, the effective pedagogical approaches and the educational strategies are supported theoretically and we believe this offers a design template for action and a way of thinking about this important aspect of preparatory nursing education. Moreover, we hope to have created a process contributing to a heighten sense of awareness in the nursing student (and other key stakeholders) of the what, how and when of clinical leadership for a novice registered nurse. The next stage is to further test through research the proposed integral curriculum thread. PMID- 26684898 TI - Exogenous Estradiol Benzoate Induces Spermatogenesis Disorder through Influencing Apoptosis and Oestrogen Receptor Signalling Pathway. AB - As the exact role for exogenous oestrogen in spermatogenesis is not fully understood, the aim of this study was to investigate the effect of estradiol benzoate (EB) exposure to male mice on their spermatogenesis and fertility. Sixty male mice aged 4 weeks were randomly divided into three groups, including a control group and two treatment groups. The mice of the control group were injected with 250 MUl paraffin oil only by every other day subcutaneous injection for 4 weeks. Meantime, the mice of the treatment groups were injected with EB at the concentration of 5 or 10 mg/kg, respectively. Results showed that EB slowed down the body weight gains and generated testicular atrophy with spermatogenesis disorder compared with that of the control mice, and consequently induced their infertility. Moreover, the number of TUNEL-positive cells in the testis of EB treated mice was significantly increased with the EB concentration rise. In comparison with controls, the mRNA expression level of pro-apoptosis factors (Fas, TNF, Cytochrome C, Apaf1, Chop, Caspase-3, Caspase-8, Caspase-9 and Caspase 12) and key genes in oestrogen receptor (ER) signalling pathway (ER alpha, ER beta, Erk1/2, Hsp90 and DAX-1) were upregulated in the testes of the treatment groups. Furthermore, Western blotting results proved the protein expression level of Fas, TNF, Cytochrome C, Chop, Caspase-3, cleaved Caspase-3, Caspase-9, Erk1/2 and Hsp90 were upregulated, and the phosphorylation level of Erk1/2 was also increased. These results indicate that EB may impair spermatogenesis through influencing the apoptosis and ER signalling pathway. PMID- 26684897 TI - Protein relative abundance patterns associated with sucrose-induced dysbiosis are conserved across taxonomically diverse oral microcosm biofilm models of dental caries. AB - BACKGROUND: The etiology of dental caries is multifactorial, but frequent consumption of free sugars, notably sucrose, appears to be a major factor driving the supragingival microbiota in the direction of dysbiosis. Recent 16S rRNA-based studies indicated that caries-associated communities were less diverse than healthy supragingival plaque but still displayed considerable taxonomic diversity between individuals. Metagenomic studies likewise have found that healthy oral sites from different people were broadly similar with respect to gene function, even though there was an extensive individual variation in their taxonomic profiles. That pattern may also extend to dysbiotic communities. In that case, shifts in community-wide protein relative abundance might provide better biomarkers of dysbiosis that can be achieved through taxonomy alone. RESULTS: In this study, we used a paired oral microcosm biofilm model of dental caries to investigate differences in community composition and protein relative abundance in the presence and absence of sucrose. This approach provided large quantities of protein, which facilitated deep metaproteomic analysis. Community composition was evaluated using 16S rRNA sequencing and metaproteomic approaches. Although taxonomic diversity was reduced by sucrose pulsing, considerable inter-subject variation in community composition remained. By contrast, functional analysis using the SEED ontology found that sucrose induced changes in protein relative abundance patterns for pathways involving glycolysis, lactate production, aciduricity, and ammonia/glutamate metabolism that were conserved across taxonomically diverse dysbiotic oral microcosm biofilm communities. CONCLUSIONS: Our findings support the concept of using function-based changes in protein relative abundance as indicators of dysbiosis. Our microcosm model cannot replicate all aspects of the oral environment, but the deep level of metaproteomic analysis it allows makes it suitable for discovering which proteins are most consistently abundant during dysbiosis. It then may be possible to define biomarkers that could be used to detect at-risk tooth surfaces before the development of overt carious lesions. PMID- 26684899 TI - 3D bioprinting of BMSC-laden methacrylamide gelatin scaffolds with CBD-BMP2 collagen microfibers. AB - Three-dimensional (3D) bioprinting combines biomaterials, cells and functional components into complex living tissues. Herein, we assembled function-control modules into cell-laden scaffolds using 3D bioprinting. A customized 3D printer was able to tune the microstructure of printed bone mesenchymal stem cell (BMSC) laden methacrylamide gelatin scaffolds at the micrometer scale. For example, the pore size was adjusted to 282 +/- 32 MUm and 363 +/- 60 MUm. To match the requirements of the printing nozzle, collagen microfibers with a length of 22 +/- 13 MUm were prepared with a high-speed crusher. Collagen microfibers bound bone morphogenetic protein 2 (BMP2) with a collagen binding domain (CBD) as differentiation-control module, from which BMP2 was able to be controllably released. The differentiation behaviors of BMSCs in the printed scaffolds were compared in three microenvironments: samples without CBD-BMP2-collagen microfibers in the growth medium, samples without microfibers in the osteogenic medium and samples with microfibers in the growth medium. The results indicated that BMSCs showed high cell viability (>90%) during printing; CBD-BMP2-collagen microfibers induced BMSC differentiation into osteocytes within 14 days more efficiently than the osteogenic medium. Our studies suggest that these function control modules are attractive biomaterials and have potential applications in 3D bioprinting. PMID- 26684900 TI - Neurofeedback of slow cortical potentials as a treatment for adults with Attention Deficit-/Hyperactivity Disorder. AB - OBJECTIVE: Attention Deficit-/Hyperactivity Disorder (ADHD) has been treated successfully in children with neurofeedback (NF). In this study, for the first time NF is investigated in adults with ADHD. To answer the question of specificity the relationship between treatment outcome and self-regulation ability is assessed. METHODS: Twenty-four participants underwent 30 sessions of slow cortical potential NF. Measurements of ADHD and comorbid symptoms, as well as neurophysiological data (reaction time (RT) and RT variability (RTV) and contingent negative variation (CNV)) were performed before and after treatment, and again six months after sessions were completed. Participants were categorized into self-regulation learners and non-learners. RESULTS: Significant improvements on all symptom scales were observed with medium to large effect sizes after treatment and six months post treatment. RT and RTV decreased significantly and there was a trend for an increased CNV. Half of the participants successfully learned to regulate their brain activity. In the long-term, symptoms in the group of learners improved more than in non-learners with large effect sizes. CONCLUSION: NF is effective in treating adult ADHD long-term. The impact of self regulation ability and possible unspecific effects still require further investigation. SIGNIFICANCE: This study is the first to investigate the effects of NF in adults with ADHD, relating clinical outcome to self-regulation performance. PMID- 26684910 TI - Biting Force and Muscle Activity in Implant-Supported Single Mandibular Overdentures Opposing Fixed Maxillary Dentition. AB - BACKGROUND: This study aimed to investigate the relation between biting force and masticatory muscle activity in patients treated by 3 modalities of single mandibular dentures. MATERIALS AND METHODS: Forty implants were placed in 10 patients with completely edentulous mandibles. The study was divided into 3 treatment stages. Initially, each patient received a conventional mandibular complete denture. At the second stage, 4 mandibular implants were placed and the denture was refitted to their abutments. Third stage comprised connecting the denture to the implants through ball attachments. During each treatment stage, maximum biting force and muscle activity were measured during maximum clenching and chewing of soft and hard food. RESULTS: Biting force demonstrated a statistically significant increase by time for the 3 treatment stages. The highest muscle activity was recorded for the conventional denture followed by the implant-supported overdenture without attachment, whereas the lowest values were recorded for the implant-supported overdenture with attachment. CONCLUSION: Biting force was related mainly to the quality of denture support. Muscle activity was higher in patients with conventional denture than with implant supported prostheses (with or without attachments). PMID- 26684894 TI - An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter? AB - BACKGROUND: Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. METHODS: The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. RESULTS: Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. CONCLUSIONS: The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. TRIAL REGISTRATION: Clinicaltrials.gov Identifier = NCT01072500. PMID- 26684902 TI - Unintended Pregnancy in the Native Hawaiian Community: Key Informants' Perspectives. AB - CONTEXT: Native Hawaiians experience the highest reported rate of unintended pregnancy of any ethnic group in Hawaii. Understanding the context in which they make decisions that influence pregnancy and pregnancy planning is essential to reducing this rate. METHODS: A qualitative study was carried out in partnership with a community health center serving a large Native Hawaiian population to explore how Native Hawaiians conceptualize pregnancy and pregnancy planning. Between August and October 2013, semistructured interviews were conducted with 10 diverse key informants from the Hawaiian community. Content analysis was used to identify themes and patterns that emerged from the interviews. RESULTS: Core Hawaiian values of children and family strongly affect how Native Hawaiians view pregnancy, pregnancy planning and unintended pregnancies. 'Ohana (families) are large and characterized by tremendous support, which is perceived to lessen the burden of an unintended pregnancy. Pregnancies, whether planned or not, are seen as blessings because children are highly valued. Because of these concepts, there is an expectation for women to continue unplanned pregnancies. Although Hawaiians ascribe value to planning pregnancies and hope that children are born under what they identify as ideal circumstances, they acknowledge that these circumstances are not necessary and often do not occur. CONCLUSION: The concepts of family and children serve as core values to Native Hawaiians and are linked to the ways in which they view pregnancy and pregnancy planning. PMID- 26684911 TI - Fabrication of 2D sheet-like BiOCl/carbon quantum dot hybrids via a template-free coprecipitation method and their tunable visible-light photocatalytic activities derived from different size distributions of carbon quantum dots. AB - A series of two-dimensional (2D) interlaced BiOCl/carbon quantum dot composites (denoted as BiOCl/CQD composites) were synthesized by a template-free coprecipitation method at room temperature, and the influence of different particle size distributions of the CQDs on the physiochemical properties and photocatalytic activities of the BiOCl/CQD composites was studied. CQDs can change the morphology and increase the specific surface area of the BiOCl/CQD composites. Moreover, the particle size distribution of the CQDs (CQD loading amount) has some effect on the light absorption, separation of photogenerated charge carriers, and photocatalytic performance of the BiOCl/CQD composites. The optimized size distribution of the CQDs is 50-150 nm. BiOCl/CQD (50-150 nm) composites showed the best improvement of light absorption and the highest photocurrent density of 0.44 MUA cm(-2), and exhibited the highest photocatalytic activity with almost 100% 2-nitrophenol removal under visible-light irradiation. The high efficacy of BiOCl/CQD (50-150 nm) composites could be attributed to their excellent light absorption and highly effective separation of photogenerated charge carriers. PMID- 26684913 TI - Implantation of a Tissue-Engineered Neo-Bile Duct in Domestic Pigs. AB - BACKGROUND: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric anastomosis (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring ascending cholangitis, secondary biliary cirrhosis). In the case of inherent extrahepatic biliary atresia or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy. METHODS: We present data on the implantation of in vitro generated neo-bile ducts in 5 domestic pigs. The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, creatinine, and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 pig. Fourteen days after implantation, the pigs were sacrificed and the bile ducts were explanted. RESULTS: All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue. CONCLUSION: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long term replacement of native bile ducts must be further evaluated. PMID- 26684912 TI - Temporal changes in the prevalence and associates of diabetes-related lower extremity amputations in patients with type 2 diabetes: the Fremantle Diabetes Study. AB - BACKGROUND: To determine temporal changes in the prevalence and associates of lower extremity amputation (LEA) complicating type 2 diabetes. METHODS: Baseline data from the longitudinal observational Fremantle Diabetes Study (FDS) relating to LEA and its risk factors collected from 1296 patients recruited to FDS Phase 1 (FDS1) from 1993 to 1996 and from 1509 patients recruited to FDS Phase 2 (FDS2) from 2008 to 2011 were analysed. Multiple logistic regression was used to determine associates of prevalent LEA in individual and pooled phases. Generalised linear modelling was used to examine whether diabetes related LEA prevalence and its associates had changed between Phases. RESULTS: There were 15 diabetes-related LEAs at baseline in FDS1 (1.2 %) and 15 in FDS2 (1.0 %; P = 0.22 after age, sex and race/ethnicity adjustment). In multivariable analysis, independent associates of a baseline LEA in FDS1 were a history of vascular bypass surgery or revascularisation, urinary albumin:creatinine ratio, peripheral sensory neuropathy and cerebrovascular disease (P <= 0.035). In FDS2, prevalent LEA was independently associated with a history of vascular bypass surgery or revascularisation, past hospitalisation for/current foot ulcer and fasting serum glucose (P <= 0.001). In pooled analyses, a history of vascular bypass or revascularisation, past hospitalisation for/current foot ulcer at baseline, urinary albumin:creatinine ratio (P < 0.001), as well as FDS Phase as a binary variable [odds ratio (95 % confidence interval): 0.28 (0.09-0.84) for FDS2 vs FDS1, P = 0.023] were associated with a lower risk of LEA at study entry. CONCLUSIONS: The risk of prevalent LEA in two cohorts of patients with type 2 diabetes from the same Australian community fell by 72 % over a 15-year period after adjustment for important between-group differences in diabetes-related and other variables. This improvement reflects primary care foot health-related initiatives introduced between Phases, and should have important individual and societal benefits against a background of a progressively increasing diabetes burden. PMID- 26684914 TI - Is the performance of ImmunoCAP ISAC 112 sufficient to diagnose peach and apple allergies? PMID- 26684915 TI - Local Polyethylene Glycol in Combination with Chitosan Based Hybrid Nanofiber Conduit Accelerates Transected Peripheral Nerve Regeneration. AB - OBJECTIVE: The incapability to promptly improve behavioral function after discontinuation of peripheral nerves is a current problem in clinical practice. Effect of local polyethylene glycol in combination with chitosan-based hybrid nanofiber conduit was assessed. STUDY DESIGN: A 10-mm sciatic nerve defect was bridged using a chitosan-based hybrid nanofiber conduit (Chitosan) filled with phosphate-buffered saline. In authograft group (AUTO), a segment of sciatic nerve was transected and reimplanted reversely. In polyethylene glycol-treated group (CHIT/PEG), the conduit was filled with polyethylene glycol solution. The regenerated fibers were studied within 12 weeks after surgery. RESULTS: The behavioral and functional tests confirmed faster recovery of the regenerated axons in PEG-treated group compared to Chitosan group (p < .05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/PEG and Chitosan groups (p < .05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers were significantly higher in CHIT/PEG than in Chitosan. In immuohistochemistry, the location of reactions to S-100 in CHIT/PEG was clearly more positive than Chitosan group. CONCLUSION: polyethylene glycol solution when loaded in a chitosan-based hybrid nanofiber conduit resulted in acceleration of functional recovery and quantitative morphometric indices of sciatic nerve. PMID- 26684916 TI - Asymptomatic bacteriuria in renal allograft recipients: not so innocent after all? PMID- 26684917 TI - Neurofibromas of the Oral Cavity: Clinical Aspects, Treatment, and Outcome. AB - OBJECTIVE: This study aimed to evaluate the efficacy of diode laser for the surgical treatment of neurofibromas (NF), in terms of clinical outcome and therapeutic success. BACKGROUND DATA: The NF is a benign tumor of the peripheral nerve sheath, characterized by the proliferation of Schwann cells, perineural cells, and endoneural fibroblasts. NF may occur as a solitary lesion, or as part of a generalized neurofibromatosis syndrome; much more rarely it occurs in the form of multiple neurofibromas with no associated syndrome. Two distinct variants of neurofibromatosis have been described: types I and II. METHODS: Ten cases are reported (6 women and 4 men, age range 43-70 years) with smooth, painful, or painless lesions of the oral mucosa. Lesions were completely excised using a diode laser at 980 nm wavelength, average power 2.0 W, in continuous wave mode, with 320 MUm optical fibers, for 45 sec average time. RESULTS: Complete healing occurred within 20 days. There were no adverse effects; patients were carefully followed up and there have been no recurrences after an interval of 3 months to 3 years. CONCLUSIONS: The results of this diode laser treatment of NF demonstrate good effectiveness of this novel therapy, which may replace conventional surgical procedures. PMID- 26684918 TI - Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab. AB - Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases. PMID- 26684919 TI - Study of gonadal hormones in Egyptian female children with sickle cell anemia in correlation with iron overload: Single center study. AB - OBJECTIVE/BACKGROUND: Sickle cell disease is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production, hemolytic anemia, and intermittent occlusion of small blood vessels, leading to tissue ischemia, chronic organ damage, and organ dysfunction including endocrine organs. The aim of this work was to evaluate some gonadal hormones in female children with sickle cell anemia (SCA) in correlation with iron overload. METHODS: This study was conducted on 40 female children with SCA with a serum ferritin of > 1000ng/mL, who were attendants at the Hematology Unit, Pediatric Department, Tanta University, Tanta, Egypt in the period from May 2012 to April 2014. Their ages ranged from 11 years to 15years and the mean age value was 12.63+/-1.36 years (Group I). Forty female children with SCA of matched age with no iron overload served as a control Group (Group II). For all patients in Groups I and II the following were performed/assessed: complete blood count, hemoglobin electrophoresis, serum iron status, serum estrogen, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). RESULTS: There were significantly higher serum ferritin and serum iron levels and significantly lower total iron binding capacity, FSH, LH, and estrogen levels in Group I compared with Group II (mean serum ferritin was 2635.1+/-918.9 in Group I vs. 292.55+/-107.2 in Group II with a p value of .001; mean serum iron was 196.3+/-55.6 in Group I vs. 120+/-16.57 in Group II with a p value of .001 and mean serum total iron binding capacity was 247.3+/-28.6 in Group I vs. 327.8.7+/-21.96 in Group II with a p value of .001; mean FSH level was 1.36+/-0.22mIU/mL in Group I vs. 2.64+/-0.81mIU/mL in Group II with a p value of .021; mean LH level was 0.11+/-0.006mIU/mL in Group I vs. 1.78+/-1.12mIU/mL in Group II with a p value of .003; mean estrogen level was 21.45+/-10.23pg/mL in Group I vs. 42.36+/-15.44pg/mL in Group II with a p value of 0.001) with significant negative correlation between serum gonadal hormones and serum ferritin (r=- .835 and p value of .01 for FSH and serum ferritin; r=- .597 and a p value of .01 for LH and serum ferritin; and r=- 0.624 and p value of .01 for estrogen and serum ferritin. CONCLUSION: Female patients with SCA with iron overload may have gonadal hormone deficiency with significant negative correlations between gonadal hormones including FSH, LH, estrogen, and serum ferritin. Recommendations include regular iron chelation for prevention of irreversible damage of the ovaries and attaining normal sexual maturation, and regular follow up for females with SCA with assessment of puberty as they are more vulnerable to develop hypogonadism and may require hormonal replacement therapy. PMID- 26684920 TI - Clotrimazole troches induce supratherapeutic blood levels of sirolimus and tacrolimus in an allogeneic hematopoietic cell-transplant recipient resulting in acute kidney injury. AB - Allogeneic hematopoietic cell transplantation is a potential curative treatment option for various malignant and nonmalignant hematologic disorders. Patients undergoing an allogeneic hematopoietic cell transplant are prescribed immune suppressant therapies to facilitate hematopoietic donor-cell engraftment and prevent graft-versus-host disease. Drug-drug interactions may occur, owing to exposure to complex multidrug regimens with narrow therapeutic windows and high toxicity profiles. Here, we describe a unique case of a 65-year-old man with poor risk acute myeloid leukemia who underwent a matched-sibling hematopoietic cell allograft. Sirolimus and tacrolimus were used for graft-versus-host disease prophylaxis. He developed oral thrush requiring treatment with clotrimazole troches, which subsequently resulted in serious renal toxicity attributed to supratherapeutic levels of sirolimus and tacrolimus. Patient renal function improved after temporarily holding both immune suppressants, and administering phenytoin to help induce sirolimus and tacrolimus metabolism. This case highlights sudden and serious toxicities that resulted from clotrimazole sirolimus and clotrimazole-tacrolimus drug-drug interactions, even when administered topically. PMID- 26684921 TI - Post-Stroke Depression: A Review. AB - Poststroke depression (PSD) has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s. Meta analyses addressing almost all major clinical issues in the field have emerged because of the relatively small number of patients included in some stroke studies. In order to build large databases, these meta-analyses have merged patients with rigorously assessed mood disorders with major depressive features with patients scoring above arbitrary cutoff points on depression rating scales, thus missing important findings such as cognitive impairment associated with major but not minor depression. Nevertheless, PSD occurs in a significant number of patients and constitutes an important complication of stroke, leading to greater disability as well as increased mortality. The most clinically important advances, however, have been in the treatment and prevention of PSD. Recent meta analyses of randomized controlled trials for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, randomized controlled trials for prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early antidepressant treatment of PSD appears to enhance both physical and cognitive recovery from stroke and might increase survival up to 10 years following stroke. There has also been progress in understanding the pathophysiology of PSD. Inflammatory processes might be associated with the onset of at least some depressive symptoms. In addition, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission might be relevant etiological factors. Further elucidation of the mechanism of PSD may ultimately lead to specific targeted treatments. PMID- 26684922 TI - Resting Hyperperfusion of the Hippocampus, Midbrain, and Basal Ganglia in People at High Risk for Psychosis. AB - OBJECTIVE: Animal models suggest that the development of psychosis involves hyperactivity in the hippocampus that drives increased activity in the midbrain and basal ganglia. The authors examined this hypothesis by measuring resting perfusion in the hippocampus, basal ganglia, and midbrain in people at high risk of psychosis. METHOD: Pseudo-continuous arterial spin labeling imaging was used to measure resting regional cerebral blood flow (rCBF) in 52 individuals at ultra high risk for psychosis and in 27 healthy volunteers. The severity of psychotic symptoms was assessed using the Comprehensive Assessment of At-Risk Mental States. The ultra-high-risk subjects were reassessed after a mean of 17 months, using the same measures as at baseline. RESULTS: At baseline, relative to healthy volunteers, ultra-high-risk subjects showed elevated rCBF in the hippocampus, basal ganglia, and midbrain. In the ultra-high-risk sample overall, at follow-up, symptomatic improvement and reduced rCBF in the hippocampus and ventral striatum were observed. Subjects whose symptoms had resolved such that they no longer met ultra-high-risk criteria showed a longitudinal reduction in left hippocampal rCBF that was not evident in subjects who remained in a high-risk state or had become psychotic. CONCLUSIONS: A high risk for psychosis was associated with increased resting activity in the hippocampus, midbrain, and basal ganglia. Subsequent resolution of the high-risk state was linked to a normalization of activity in these regions. These findings are consistent with animal models that propose that psychotic symptoms may be generated when hippocampal hyperactivity drives hyperactivity in regions involved in subcortical dopamine signaling. PMID- 26684924 TI - Opioids in Psychiatric Disorders: Back to the Future? PMID- 26684923 TI - Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial. AB - OBJECTIVE: Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation. METHOD: This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment. RESULTS: Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference -4.3, 95% CI=-8.5, -0.2) and after 4 weeks (mean difference=-7.1, 95% CI=-12.0, -2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial. CONCLUSIONS: The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment. PMID- 26684925 TI - The role of CuCl on the mechanism of dibenzo-p-dioxin formation from poly chlorophenol precursors: A computational study. AB - A computational study is performed for the elucidation of the role played by CuCl in the condensation of two polychlorophenol molecules to yield PCDDs. The mechanism found consists of six sequential steps, which allow the final recuperation of the CuCl molecule, and applies for phenol molecules with an ortho chlorine. In the temperature range of 453-473 K (previously reported as adequate to diminish PCDDs formation in the post-combustion area), CuCl is able to softly retain chlorophenol molecules, mainly those less chlorinated. After a first HCl release, Cu(I) remains bonded to phenol oxygen atom, thus avoiding the formation of phenoxy radicals and the subsequent radical processes. A temperature raise up to 1200 K destabilizes the initial CuCl-chlorophenol complexes and causes that the rate limiting step change from the formation of the first oxygen bridge to HCl elimination. It has been checked that tetra and penta-chlorophenols undergo essentially the same reaction process of 2-chlorophenol. In view of our results and trying to arrive at a practical way to diminish the rate of formation of PCDDs, we propose that an extra addition of powdered CuCl to the post-combustion zone, cooled down to temperatures lower than 473 K, could act as an inhibitor in the formation of these pollutants. PMID- 26684926 TI - Characterization and Immunogenicity of Outer Membrane Vesicles from Brucella abortus. AB - Bovine brucellosis is a worldwide spread zoonotic disease. The objectives of this study were characterization of outer membrane vesicles from B. abortus and to evaluate their immunogenicity in mice. For this purpose, OMVs were derived from B. abortus strain 99 using ultracentrifugation method. Isolated OMVs were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis and transmission electron microscopy which revealed spherical 20-300 nm structures rich in proteins. OMVs also showed immuno-reactivity with mice antisera in Western blot. Further, indirect ELISA showed specific and high-titer immune responses against the antigens present in OMVs suggesting their potential for a safe acellular vaccine candidate. PMID- 26684927 TI - Aggregation Behavior of Several Ionic Liquids in Molecular Solvents of Low Polarity--Indication of a Bimodal Distribution. AB - The structure and dynamics of ion pairing and aggregation is studied by concentration- and temperature-dependent measurements of (1) H and (19) F self diffusion coefficients, viscosity, and conductivity for the following five solutions: 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([Cn mim][NTf2], n=2, 4, 6) in dichloromethane (CH2Cl2), and [C6 mim][NTf2] in tetrahydrofuran (THF) and chlorobenzene (C6 H5 Cl). The temperature dependence of these properties at constant IL concentrations follows the Arrhenius law for all five solutions. The IL-concentration dependence of the respective activation energies obtained from the Arrhenius analysis is nonlinear in the case of conductivity, but indicates linear relationships for viscosity and self diffusion. All five solutions studied display average solute radius maxima as plotted against IL concentration. The maximum average solute radii follow an order of solvents of CHCl3 >C6 H5 Cl>CH2 Cl2 ~THF, which corresponds to the order of increasing solvent dielectric constant. The observed trends in the physical properties of these solutions indicate the development of a bimodal distribution of solute size with increasing IL concentration. Specifically, the presence of aggregates is supported by the analysis of the conductivity data and the observation of the same self-diffusion coefficients for the cation and anion. The concurrent presence of freely dissolved ions is supported by the obtained average solute radii that do not exceed the radii of the corresponding ion pairs. PMID- 26684928 TI - Passenger Gene Mutations: Unwanted Guests in Genetically Modified Mice. PMID- 26684929 TI - Children with dermatological conditions admitted to paediatric intensive care: analysis of a national clinical audit database. AB - There is little published literature about dermatological conditions in paediatric intensive care units (PICUs). The aim of this study was to describe the range of skin disorders in children admitted to PICUs in the UK and Ireland using data from a national audit. An analysis was conducted using data for 2002 - 2010 from the Paediatric Intensive Care Audit Network (PICANet). In total, 999 admissions of 882 children were identified, representing 0.8% of all PICU admissions. The most frequent dermatological conditions were skin infections, including cellulitis and necrotizing fasciitis, and inflammatory conditions. In 28% of cases, the dermatological diagnosis was considered the reason for PICU admission, in 35% it was a manifestation of systemic disease and in 37% it was considered incidental. Overall mortality was similar to the general PICU population, with 52 deaths (5.2%), but was greater in children with vascular/haematological conditions. PMID- 26684930 TI - argyle: An R Package for Analysis of Illumina Genotyping Arrays. AB - Genotyping microarrays are an important and widely-used tool in genetics. I present argyle, an R package for analysis of genotyping array data tailored to Illumina arrays. The goal of the argyle package is to provide simple, expressive tools for nonexpert users to perform quality checks and exploratory analyses of genotyping data. To these ends, the package consists of a suite of quality control functions, normalization procedures, and utilities for visually and statistically summarizing such data. Format-conversion tools allow interoperability with popular software packages for analysis of genetic data including PLINK, R/qtl and DOQTL. Detailed vignettes demonstrating common use cases are included as supporting information. argyle bridges the gap between the low-level tasks of quality control and high-level tasks of genetic analysis. It is freely available at https://github.com/andrewparkermorgan/argyle and has been submitted to Bioconductor. PMID- 26684933 TI - Treatment of Secondary Hyperparathyroidism: Results of a Phase 2 Trial Evaluating an Intravenous Peptide Agonist of the Calcium-Sensing Receptor. AB - BACKGROUND/AIMS: This study evaluated the efficacy and safety of AMG416 (etelcalcitide), a novel peptide agonist of the calcium (Ca)-sensing receptor given intravenously (IV) after each hemodialysis session for the treatment of secondary hyperparathyroidism (SHPT). METHODS: Adult subjects with SHPT on hemodialysis enrolled in a 12-week, dose titration (parent) study followed by an open-label extension phase. AMG416 was administered IV, thrice weekly starting at 5 mg/session and titrated based on the subject's parathyroid hormone (PTH) and albumin-corrected Ca (cCa) to target a PTH of 150-300 pg/ml. Efficacy (percent PTH change from baseline to the efficacy analysis period during the parent study) and safety (open-label extension phase) endpoints were evaluated. RESULTS: Baseline (n = 37) mean (standard error [SE]) PTH was 853 (106 pg/ml). The mean (95% CI) percent change from baseline to the efficacy analysis period in PTH concentration was -53.6% (-60.8, -46.4). The proportion of subjects with >=30% reduction in PTH from baseline to the efficacy assessment period (EAP) was 89% (32/36; 95% CI 73.9, 96.9). Results by the baseline PTH subgroup (<=700 vs. >700 pg/ml) were comparable for both analyses. The proportion of subjects achieving a PTH <=300 pg/ml was 56% (n = 20/36) at the efficacy assessment period. The mean (SE) percent changes from baseline to EAP were observed for cCa -15% (1.0%) and phosphorus -10% (3.3%). Adverse events were mild to moderate in severity. The PTH reductions achieved in the parent study were maintained in the open-label extension phase. CONCLUSION: AMG416 was well tolerated and appears to be an effective agent for the treatment of SHPT in patients on hemodialysis. PMID- 26684932 TI - Will Culling White-Tailed Deer Prevent Lyme Disease? AB - White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances. PMID- 26684931 TI - The Mouse Universal Genotyping Array: From Substrains to Subspecies. AB - Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the Mouse Universal Genotyping Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus). The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control. PMID- 26684934 TI - Structural and Biochemical Characterizations of Methanoredoxin from Methanosarcina acetivorans, a Glutaredoxin-Like Enzyme with Coenzyme M-Dependent Protein Disulfide Reductase Activity. AB - Glutaredoxins (GRXs) are thiol-disulfide oxidoreductases abundant in prokaryotes, although little is understood of these enzymes from the domain Archaea. The numerous characterized GRXs from the domain Bacteria utilize a diversity of low molecular-weight thiols in addition to glutathione as reductants. We report here the biochemical and structural properties of a GRX-like protein named methanoredoxin (MRX) from Methanosarcina acetivorans of the domain Archaea. MRX utilizes coenzyme M (CoMSH) as reductant for insulin disulfide reductase activity, which adds to the diversity of thiol protectants in prokaryotes. Cell free extracts of M. acetivorans displayed CoMS-SCoM reductase activity that complements the CoMSH-dependent activity of MRX. The crystal structure exhibits a classic thioredoxin-glutaredoxin fold comprising three alpha-helices surrounding four antiparallel beta-sheets. A pocket on the surface contains a CVWC motif, identifying the active site with architecture similar to GRXs. Although it is a monomer in solution, the crystal lattice has four monomers in a dimer of dimers arrangement. A cadmium ion is found within the active site of each monomer. Two such ions stabilize the N-terminal tails and dimer interfaces. Our modeling studies indicate that CoMSH and glutathione (GSH) bind to the active site of MRX similar to the binding of GSH in GRXs, although there are differences in the amino acid composition of the binding motifs. The results, combined with our bioinformatic analyses, show that MRX represents a class of GRX-like enzymes present in a diversity of methane-producing Archaea. PMID- 26684935 TI - No Matter What Concentration, Automated Fluid Control Increases the Safety of Regional Citrate Anticoagulation in Plasma Exchange. PMID- 26684936 TI - Antibodies against neo-epitope tTg complexed to gliadin are different and more reliable then anti-tTg for the diagnosis of pediatric celiac disease. AB - The neo-epitope tTg (tTg-neo) autoantibody, never challenged the anti-tissue transglutaminase (tTg) premiership, recommended by ESPGHAN, for celiac disease (CD) diagnosis. Pediatric CD (PCD), abdominal pains and normal children, normal adults, and rheumatoid arthritis patients, were tested using the following ELISAs detecting IgA, IgG or both IgA and IgG (check): AESKULISA(r) tTg (tTg; RUO) and AESKULISA(r) tTg-neo. Higher OD activity was detected for tTg-neo IgA, IgG and IgA+IgG than for tTg. tTg-neo IgA, IgG correlated better with intestinal damage than tTg. The tTg-neo combined IgA+IgG ELISA kit had higher sensitivity and a comparable specificity for the diagnosis of PCD. The drop in the % competition was much higher with the tTg-neo then the tTg antibodies. The false positivity of the tTg was significantly higher than the tTg-neo one. Serological diagnostic performances, reflection of intestinal damage, diverse epitopes and false positivity were better with the tTg-neo. PMID- 26684937 TI - Study of dendritic cell migration using micro-fabrication. AB - Cell migration is a hallmark of dendritic cells (DCs) function. It is needed for DCs to scan their environment in search for antigens as well as to reach lymphatic organs in order to trigger T lymphocyte's activation. Such interaction leads to tolerance in the case of DCs migrating under homeostatic conditions or to immunity in the case of DCs migrating upon encounter with pathogen-associated molecular patterns. Cell migration is therefore essential for DCs to transfer information from peripheral tissues to lymphoid organs, thereby linking innate to adaptive immunity. This stresses the need to unravel the molecular mechanisms involved. However, the tremendous complexity of the tissue microenvironment as well as the limited spatio-temporal resolution of in vivo imaging techniques has made this task difficult. To bypass this problem, we have developed microfabrication-based experimental tools that are compatible with high resolution imaging. Here, we will discuss how such devices can be used to study DC migration under controlled conditions that mimic their physiological environment in a robust quantitative manner. PMID- 26684940 TI - Lab Animal is turning 45. PMID- 26684938 TI - Atrial Overdrive Pacing: Is VA Linking Present? PMID- 26684941 TI - Smell carries social signals among macaques. PMID- 26684944 TI - A new light switch for optogenetics. PMID- 26684942 TI - A mechanism for magnetosensing in animals. PMID- 26684945 TI - Understanding the hearts of mice and men. PMID- 26684947 TI - Birds of a feather flock--and sing--together. PMID- 26684948 TI - Response to Protocol Review Scenario: Request for more information. PMID- 26684949 TI - When reducing numbers might increase pain. PMID- 26684950 TI - Response to Protocol Review Scenario: Welfare comes first. PMID- 26684951 TI - Response to Protocol Review Scenario: The answers are in experimental design. PMID- 26684952 TI - A word from OLAW. PMID- 26684954 TI - How to determine humane endpoints for research animals. PMID- 26684953 TI - Altered states part 1: ancillary refinements in managing perioperative distress with canines. AB - The biomedical research community has made great progress over the last 30 years in improving strategies to detect and manage pain. Managing experimental and procedural anxiety is a more challenging task, and it depends on the continued practice of distinguishing normal and abnormal states of physiology and behavior in animal subjects. Common approaches for managing pain and distress can be optimized by implementing a plan to also monitor and manage anxiety and dysphoria. PMID- 26684955 TI - Percutaneous microembolization of the left coronary artery to model ischemic heart disease in rats. AB - Small animal models of myocardial infarction are used for a wide variety of research purposes, but common techniques for generating such models require thoracic surgeries that increase mortality risk and damage important structures, such as the pericardial sac. Here, we describe a technique for modeling myocardial infarction in rats by selective coronary microembolization, which has hitherto been described only in large animals. This technique selectively catheterizes the left coronary artery using a custom-made catheter that is introduced and precisely placed under fluoroscopic guidance. Microspheres are then injected through the catheter to cause embolization. This process creates multiple simultaneous micro-infarcts that resemble those from clinical embolization after a percutaneous coronary intervention. As this technique does not require thoracic surgery, a low attrition rate was expected and once it was optimized, this technique had a low mortality rate of just 14% during experimental application. This technique creates infarcts that appear small but are associated with transient ECG changes and a persistently lower ejection fraction after embolization. Microspheres are retained in the myocardial tissue and are visible by epifluorescent microscopy after histological staining and recognizable as a distinct speckle pattern in ultrasound images. PMID- 26684956 TI - Lack of adverse effects during a target animal safety trial of extended-release buprenorphine in Fischer 344 rats. AB - Extended-release buprenorphine is an effective analgesic in laboratory animals, and its safety has been established in mice but not in rats. The authors used a target animal safety trial to evaluate the safety of extended-release buprenorphine in rats. Fischer 344 rats received post-surgical subcutaneous injections of 1.3 mg, 3.9 mg or 6.5 mg buprenorphine per kg body weight (two times, six times or ten times the intended dose, respectively), and their body weight, clinical signs and symptoms, clinical pathology and histopathology were monitored for 4 d. Body weight was not significantly different in rats that received buprenorphine compared with control rats. Signs of nausea-related behavior were observed in 25% of the rats treated with buprenorphine. Clinical pathology results for all rats were normal, and gross and microscopic histopathology examinations identified no substantial abnormalities, suggesting that this behavior was of minor consequence. Other adverse events previously reported to occur with opiate therapy, including weight loss and dermal lesions at drug injection sites, were not observed in this study. The results of this study show that post-surgical administration of an extended-release buprenorphine product is safe in Fischer 344 rats and does not necessarily cause substantial adverse effects, confirming that opiate therapy is a viable choice in laboratory animal medicine. PMID- 26684957 TI - Blood profiles in unanesthetized and anesthetized guinea pigs (Cavia porcellus). AB - The guinea pig is a common animal model that is used in biomedical research to study a variety of systems, including hormonal and immunological responses, pulmonary physiology, corticosteroid response and others. However, because guinea pigs are evolutionarily a prey species, they do not readily show behavioral signs of disease, which can make it difficult to detect illness in a laboratory setting. Minimally invasive blood tests, such as complete blood counts and plasma biochemistry assays, are useful in both human and veterinary medicine as an initial diagnostic technique to rule in or rule out systemic illness. In guinea pigs, phlebotomy for such tests often requires that the animals be anesthetized first. The authors evaluated hematological and plasma biochemical effects of two anesthetic agents that are commonly used with guinea pigs in a research setting: isoflurane and a combination of ketamine and xylazine. Hematological and plasma biochemical parameters were significantly different when guinea pigs were under either anesthetic, compared to when they were unanesthetized. Plasma proteins, liver enzymes, white blood cells and red blood cells appeared to be significantly altered by both anesthetics, and hematological and plasma biochemical differences were greater when guinea pigs were anesthetized with the combination of ketamine and xylazine than when they were anesthetized with isoflurane. Overall these results indicate that both anesthetics can significantly influence hematological and plasma biochemical parameters in guinea pigs. PMID- 26684958 TI - What is your mindset about learning? PMID- 26684959 TI - Roles for Transcription Factors Sp1, NF-kappaB, IRF3, and IRF7 in Expression of the Human IFNL4 Gene. AB - The expression of a biologically active human IFNlambda4 depends on the presence of a frameshift deletion polymorphism within the first exon of the interferon lambda 4 (IFNL4) gene. In this report, we use the lung carcinoma-derived cell line, A549, which is genetically viable to express a functional IFNlambda4, to address transcriptional requirements of the IFNL4 gene. We show that the GC-rich DNA-binding transcription factor (TF) specificity protein 1 (Sp1) is recruited to the IFNL4 promoter and has a role in induction of gene expression upon stimulation with viral RNA mimic poly(I:C). By using RNAi and overexpression strategies, we also show key roles in IFNL4 gene expression for the virus inducible TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappaB), IFN regulatory factor 3 (IRF3), and IRF7. Interestingly, we also observe that overexpression of IFNlambda4 influences IFNL4 promoter activity, which may further be dependent on the retinoic acid-inducible gene-I (RIG-I)-like receptor pathway. Together, our work for the first time reports on the functional characterization of the human IFNL4 promoter. PMID- 26684960 TI - Randomized controlled trial of computerized alcohol intervention for college students: role of class level. AB - BACKGROUND: Because of their ability to reach a much wider audience than face-to face counseling or psychoeducation, computer-delivered interventions for risky or potentially problematic use have been increasing on college campuses. However, there are very few studies that examine who benefits most from such interventions. OBJECTIVES: The purpose of this study was to determine if participation in Alcohol-Wise, a computerized intervention, is associated with changes in alcohol drinking behavior and its consequences, perceptions of college drinking norms, and expectancies. It was hypothesized that class level (i.e. freshman/sophomore versus junior/senior) would moderate the effectiveness of Alcohol-Wise. METHOD: College students (n = 58) were randomly assigned to one of two conditions: (i) the computer-delivered intervention or (ii) wait-list control. Measures were completed at baseline and approximately 30-days later. RESULTS: At follow-up, freshman and sophomore students in the intervention group showed significant reduction in peak number of standard drinks and blood alcohol concentration, but the effect was not observed for juniors and seniors. The intervention group reported more accurate estimates of drinking norms at follow up relative to controls. There were no significant changes over time in alcohol expectancies in either group. CONCLUSION: This study provides support for the potential usefulness of Alcohol-Wise intervention at reducing short-term drinking among underclassmen but not upperclassmen in a 4-year college setting. These findings suggest that computerized interventions may be more effective when provided early, but not later, in a student's college career. PMID- 26684961 TI - An evaluation of factors influencing the assessment time in a nurse practitioner led anaesthetic pre-operative assessment clinic. AB - Elective patients undergoing anaesthetic pre-operative assessment are usually allocated the same period of time with a nurse practitioner, leading to potential inefficiencies in patient flow through the clinic. We prospectively collected data on 8519 patients attending a pre-operative assessment clinic. The data set were split into derivation and validation cohorts. Standard multiple regressions were used to construct a model in the derivation cohort, which was then tested in the validation cohort. Due to missing data, 2457 patients were not studied, leaving 5892 for analysis (3870 in the derivation cohort and 2022 in the validation cohort). The mean (SD) pre-operative assessment time was 46 (12) min. Age, ASA physical status, nurse practitioner and surgical specialty all influenced the time spent in pre-operative assessment. The predictive equations calculated using the derivation cohort, based on age and ASA physical status, correctly estimated duration of consultation to within 20% of the maximum predicted time in 74.2% of the validation cohort. We conclude that if age and ASA physical status are known before the pre-operative assessment consultation, it could allow appointment times to be allocated more accurately. PMID- 26684962 TI - Stereoselective Alkali-Metal Catalysts for Highly Isotactic Poly(rac-lactide) Synthesis. AB - A high degree of chain end control in the isoselective ring-opening polymerization (ROP) of rac-lactide is a challenging research goal. In this work, eight highly active sodium and potassium phenolates as highly isoselective catalysts for the ROP of rac-lactide are reported. The best isoselectivity value of Pm = 0.94 is achieved. The isoselective mechanism is chain-end control through the analysis of the stereoerrors in the microstructure of a final polymer; thus, isotactic multiblock structure polymers are obtained, and the highest melt point can reach 192.5 degrees C. The donating group in phenolate can clearly accelerate the ROP reaction, potassium complexes are more active than the analogous sodium complexes, and the big spacial hindrance of the ligand can decrease the activity. The high isoselectivities of these complexes mostly result from their sandwich structure constructed by the plane of the crown and the plane of the anthryl group. PMID- 26684964 TI - All adults once were children. AB - All adults once were children, and children exposed to unrelenting adversities or toxic stress are at risk for developing a multitude of health conditions that threaten their development and eventual adult health status. Pediatricians and their pediatric surgeon colleagues can help families and their children develop resiliency by properly addressing the needs of families and their children and by participating in advocacy opportunities related to federal, state, and local policies affecting children. Evolving neuroscience that expands our knowledge of brain health and the relatively new field of epigenetics continue to contribute scientific information that underscores the need for attention to the health and wellbeing of the developing child in order to prevent many diseases and conditions among adults that continue to escalate healthcare costs. Resiliency is needed to combat the effects of toxic stress, and physicians are urged to work with their communities to assist families who need help learning about parenting resources to promote children's capacities for success. PMID- 26684963 TI - Neighborhood-level social processes and substantiated cases of child maltreatment. AB - Child maltreatment is a preventable public health problem. Research has demonstrated that neighborhood structural factors (e.g. poverty, crime) can influence the proportion of a neighborhood's children who are victims of maltreatment. A newer strategy is the identification of potentially modifiable social processes at the neighborhood level that can also influence maltreatment. Toward this end, this study examines neighborhood-level data (maltreatment cases substantiated by Illinois' child protection agency, 1995-2005, social processes measured by the Project on Human Development in Chicago Neighborhoods, U.S. Census data, proportions of neighborhoods on public assistance, and crime data) that were linked across clusters of contiguous, relatively homogenous Chicago, IL census tracts with respect to racial/ethnic and socioeconomic composition. Our analysis-an ecological-level, repeated cross-sectional design utilizing random intercept logit models-with a sensitivity analysis using spatial models to control for spatial autocorrelation-revealed consistent associations between neighborhood social processes and maltreatment. Neighborhoods higher in collective efficacy, intergenerational closure, and social networks, and lower in disorder had lower proportions of neglect, physical abuse, and sexual abuse substantiated cases, controlling for differences in structural factors. Higher collective efficacy and social network size also predicted a lower proportion of substance-exposed infants. This research indicates that strategies to mobilize neighborhood-level protective factors may decrease child maltreatment more effectively than individual and family-focused efforts alone. PMID- 26684965 TI - Dealing With Unintended Consequences: Continuous-Flow LVADs and Aortic Insufficiency. PMID- 26684966 TI - Longitudinal Strain as Risk Factor for Outcome in Pediatric Dilated Cardiomyopathy. PMID- 26684967 TI - Vortex Formation Time Index in Patients With Hypertrophic Cardiomyopathy. PMID- 26684969 TI - Myocardial ECV Fraction Assessed by CMR Is Associated With Type of Hemodynamic Load and Arrhythmia in Repaired Tetralogy of Fallot. AB - OBJECTIVES: The aim of this study was to investigate the extent of diffuse myocardial fibrosis by measuring left (LV) and right ventricular (RV) extracellular volume fraction (ECV) in patients with repaired tetralogy of Fallot (rTOF) and to explore its association with ventricular remodeling, hemodynamic load, and clinical parameters. BACKGROUND: Focal myocardial fibrosis is prevalent in patients with rTOF. However, little is known about the extent of diffuse myocardial fibrosis and its clinical implications in this population. METHODS: We measured ECV by pre- and post-gadolinium T1 measurements using a 1.5-T scanner in 84 patients with rTOF (median age 23.3 years). LV ECV was determined by averaging values from 6 short-axis mid-ventricular segments, and RV ECV was calculated by averaging values from the anterior-inferior and the diaphragmatic RV wall segments. RESULTS: LV ECV above the upper limit of normal (>28%) was observed in 11 patients and for RV ECV (>41%) in 9 patients. LV ECV correlated positively with RV ECV (r = 0.54; p < 0.001). Greater RV ECV was associated with female gender, lower RV mass-to-volume ratio, lower RV outflow tract pressure gradient, and having volume overload as the predominant hemodynamic burden (all p < 0.001). Similar associations were observed with LV ECV. In multivariable analysis, increased LV ECV was independently associated with arrhythmia, adjusting for age and RV mass index (odds ratio: 5.69; p = 0.031). CONCLUSIONS: In this cohort, LV and RV ECV values were positively correlated, indicating an adverse ventricular ventricular interaction at the tissue level. Increased ECV was associated with RV volume overload and arrhythmia. These findings may lead to future studies exploring the role of ECV in improving risk stratification and guiding therapeutic interventions. PMID- 26684968 TI - Plaque Volume of Carotid Endarterectomy Specimens Measured by 3D Ultrasound Technology. PMID- 26684971 TI - Reversing the Substrate for Atrial Fibrillation With CRT? PMID- 26684970 TI - T1 Mapping by CMR Imaging: From Histological Validation to Clinical Implication. AB - OBJECTIVES: The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies. BACKGROUND: Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established. METHODS: A total of 473 consecutive patients referred for CMR (49.5% female, age 57.8 +/- 17.1 years) without hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson Fabry disease were studied. T1 mapping with the modified Look-Locker inversion recovery (MOLLI) sequence was used for ECV calculation (CMR-ECV). For methodological validation, 36 patients also underwent left ventricular biopsy, and ECV was quantified by TissueFAXS analysis (TissueFAXS-ECV). To assess the prognostic value of CMR-ECV, its association with hospitalization for cardiovascular reasons or cardiac death was tested in a multivariable Cox regression model. RESULTS: TissueFAXS-ECV was 26.3 +/- 7.2% and was significantly correlated with CMR-ECV (r = 0.493, p = 0.002). Patients were followed up for 13.3 +/- 9.0 months and divided into CMR-ECV tertiles for Kaplan-Meier analysis (tertiles were <= 25.7%, 25.8% to 28.5%, and >= 28.6%). Significantly higher event rates were observed in patients with higher CMR-ECV (log-rank p = 0.013). By multivariable Cox regression analysis, CMR-ECV was independently associated with outcome among imaging variables (p = 0.004) but not after adjustment for clinical parameters. CONCLUSIONS: CMR T1 mapping allows accurate noninvasive quantification of ECV and is independently associated with event-free survival among imaging parameters. Its prognostic value on top of established clinical risk factors warrants further investigation in long-term studies. PMID- 26684972 TI - Determinants of New-Onset Atrial Fibrillation in Patients Receiving CRT: Mechanistic Insights From Speckle Tracking Imaging. AB - OBJECTIVES: The aim of this study was to investigate the factors associated with the development of atrial fibrillation (AF) and to examine the impact of these factors for long-term outcome after cardiac resynchronization therapy (CRT). BACKGROUND: The effect of CRT on the development of new AF is under debate. METHODS: Clinical assessment, 12-lead electrocardiogram, echocardiography with speckle tracking strain imaging, and device interrogation before implantation and every 6 months thereafter were performed regularly over a 5-year follow-up. The primary endpoint was new-onset AF. Pre-specified outcome events were transplantation, assist device implantation, and death. RESULTS: During follow up, AF occurred in 29 of 106 patients. Parameters of left atrial (LA) mechanics including mitral annular (A') velocity, left atrial volume index (LAVI), LA ejection fraction, active emptying fraction, LA mean systolic strain (Ss) and late diastolic strain (Sa) improved at 6 months only in patients who remained free of AF. The change in LA Ss and Sa from baseline to 6 months after CRT had the highest accuracy to predict new-onset AF (area under the curve [AUC] = 0.793, 0.815, respectively, p < 0.0001 for both vs. left ventricular [LV] reverse remodeling AUC = 0.531; p < 0.01 for both). In addition, the change in LA Ss and Sa predicted outcome events independently from new-onset AF and LV volume response. CONCLUSIONS: LA functional improvement is essential for AF-free survival after CRT and is an independent predictor of AF-free survival. The improvement in LA Ss and Sa as a means of LA mechanical reserve also predicts long-term event-free survival after CRT independently from LV volume response and new-onset AF. PMID- 26684973 TI - Current State of Advanced Cardiovascular Imaging Training in the United States. PMID- 26684974 TI - Is Biventricular Fibrosis the Mediator of Late Complications in Tetralogy of Fallot? PMID- 26684975 TI - Accurate Quantification Methods for Aortic Insufficiency Severity in Patients With LVAD: Role of Diastolic Flow Acceleration and Systolic-to-Diastolic Peak Velocity Ratio of Outflow Cannula. AB - OBJECTIVES: The aim of this study was to develop a technique to measure regurgitant flow throughout the entire cardiac cycle that would more accurately measure aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs). BACKGROUND: AI is a common problem after CF-LVAD implantation. Current echocardiographic evaluation of AI does not take into account the unique flow properties present in patients with CF-LVADs. METHODS: In this prospective study, patients with LVADs who had varying degrees of AI (N = 20) underwent simultaneous right-sided heart catheterization (RHC) and transthoracic echocardiography (TTE). Regurgitant fraction (RF) across the aortic valve was calculated by subtracting the cardiac output obtained using the Fick method from the total systemic flow measured using the sum of the product of the velocity time integral and the cross-sectional area of the LVAD outflow cannula and aortic valve, respectively. The RFs were then compared with the following: 1) traditional TTE grading parameters; and 2) new TTE parameters unique to LVAD physiology, namely the diastolic flow acceleration and the systolic-to-diastolic peak velocity (S/D) ratio of the LVAD outflow cannula. RESULTS: Patients without evidence of AI had an RF approaching zero (2.4 +/- 4.6%). Patients with trace and mild AI had an RF of 31.0 +/- 5.4%, whereas patients with moderate or severe AI had an RF of 45.8 +/- 3.6%. RF correlated better with pulmonary capillary wedge pressure (PCWP) than with vena contracta (correlation coefficient [R] = 0.73 vs. 0.56). The new TTE parameters (S/D ratio and diastolic acceleration) highly correlated with RF (R = 0.91 and 0.94, respectively) and more strongly correlated with PCWP than did vena contracta (R = 0.82 and 0.65 vs. 0.56). CONCLUSIONS: RF measured by simultaneous RHC and TTE better correlates with clinical filling pressures than do traditional TTE parameters and may identify significant AI that could be underestimated using conventional measures. Novel TTE parameters, unique to CF-LVAD physiology, better correlate with RF and filling pressures than do our current TTE measurements. PMID- 26684976 TI - Diffuse LV Myocardial Fibrosis and its Clinical Associations in Adults With Repaired Tetralogy of Fallot. PMID- 26684977 TI - Is Myocardial Native T1 the One Answer for All? PMID- 26684979 TI - Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti-Inflammatory Agents. AB - Two series of new 1-(alkyl/aryl)-3-{2-[(5-oxo-4,5-dihydro-1H-pyrazol-3 yl)amino]phenyl}thioureas 2a-h and 5-[2-(substituted amino)-1H-benzimidazol-1-yl] 4H-pyrazol-3-ols 3a-i were designed and synthesized as anti-inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non-selective inhibition of COX-1 and COX 2 enzymes which was consistent with their docking results. Compounds 2c, 2f, 2g, 3b, and 3g that showed the highest COX-2 inhibitory activity were selected for further in vivo testing as anti-inflammatory agents using diclofenac as a reference drug. Two of the test compounds (2c and 3b) showed potent anti inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti-inflammatory agents was also provided. PMID- 26684978 TI - Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents. AB - OBJECTIVES: The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. BACKGROUND: In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. METHODS: Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. RESULTS: Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 +/- 19 ms at 1.5-T; 1,189 +/- 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 +/- 0.5% at 1.5-T; 6.3 +/- 1.1% at 3.0-T; all p < 0.0001). Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 +/- 84 ms), without significant T1 reactivity (0.2 +/- 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 +/- 17 ms; p < 0.001) without significant T1 reactivity (0.2 +/- 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 +/- 17 ms; p = 0.92), showed blunted T1 reactivity (3.9 +/- 0.6%; p < 0.001). CONCLUSIONS: T1 mapping at rest and during adenosine stress can differentiate between normal, infarcted, ischemic, and remote myocardium with distinctive T1 profiles. Stress/rest T1 mapping holds promise for ischemia detection without the need for gadolinium contrast. PMID- 26684980 TI - Letter to the Editor: Re: Bruxism is Unlikely to Cause Damage to the Periodontium: Findings from a Systematic Literature Assessment. PMID- 26684981 TI - Letter to the Editor: Authors' Response. PMID- 26684982 TI - Curative laser thermoablation of epilepsy secondary to bottom-of-sulcus dysplasia near eloquent cortex. PMID- 26684983 TI - Clinical Trial Registration: The Time Has Come.... PMID- 26684984 TI - Bilateral congenital lumbar hernias in a patient with central core disease--A case report. AB - Congenital lumbar hernias are rare malformations caused by defects in the development of the posterior abdominal wall. A known association exists with lumbocostovertebral syndrome; however other associated anomalies, including one case with arthrogryposis, have been previously reported. We present an infant girl with bilateral congenital lumbar hernias, multiple joint contractures, decreased muscle bulk and symptoms of malignant hyperthermia. Molecular testing revealed an R4861C mutation in the ryanodine receptor 1 (RYR1) gene, known to be associated with central core disease. This is the first reported case of the co occurrence of congenital lumbar hernias and central core disease. We hypothesize that ryanodine receptor 1 mutations may interrupt muscle differentiation and development. Further, this case suggests an expansion of the ryanodine receptor 1 related myopathy phenotype to include congenital lumbar hernias. PMID- 26684985 TI - The efficient role of aquatic plant (water hyacinth) in treating domestic wastewater in continuous system. AB - In this study, water hyacinth (Eichhornia crassipes) was used to treat domestic wastewater. Ten organic and inorganic parameters were monitored in three weeks for water purification. The six chemical, biological and physical parameters included Dissolved Oxygen (DO), Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Ammoniacal Nitrogen (NH3-N), Total Suspended Solids (TSS), and pH were compared with the Interim National Water Quality Standards, Malaysia River classification (INWQS) and Water Quality Index (WQI). Between 38% to 96% of reduction was observed and water quality has been improved from class III and IV to class II. Analyses for Electricity Conductivity (EC), Salinity, Total Dissolved Solids (TDS) and Ammonium (NH4) were also investigated. In all parameters, removal efficiency was in range of 13-17th day (optimum 14th day) which was higher than 3 weeks except DO. It reveals the optimum growth rate of water hyacinth has great effect on waste water purification efficiency in continuous system and nutrient removal was successfully achieved. PMID- 26684986 TI - Social relationship satisfaction and PTSD: which is the chicken and which is the egg? AB - BACKGROUND: Impaired social relationships are linked with higher levels of posttraumatic stress disorder (PTSD), but the association's underlying dynamics are unknown. PTSD may impair social relationships, and, vice versa, poorer relationship quality may interfere with the recovery from PTSD. OBJECTIVE: This work longitudinally evaluates the simultaneous progression of PTSD symptoms and social relationship satisfaction (SRS) in a large cohort of recent trauma survivors. It also explores the effect of cognitive behavior therapy (CBT) on the association between the two. METHOD: Consecutive emergency department trauma admissions with qualifying PTSD symptoms (n=501) were assessed 3 weeks and 5 months after trauma admission. The World Health Organization Quality of Life evaluated SRS and the Clinician Administered PTSD Scale evaluated PTSD symptom severity. Ninety-eight survivors received CBT between measurement sessions. We used Structural Equation Modeling to evaluate cross-lagged effects between the SRS and PTSD symptoms. RESULTS: The cross-lagged effect of SRS on PTSD was statistically significant (beta=-0.12, p=0.01) among survivors who did not receive treatment whilst the effect of PTDS on SRS was nil (beta=-0.02, p=0.67). Both relationships were non-significant among survivors who received CBT. DISCUSSION: SRS and PTSD are highly associated, and this study shows that changes in SRS in the early aftermath of traumatic events contribute to changes in PTSD, rather than vice versa. SRS impacts natural recovery, but not effective treatment. This study suggests that being satisfied with one's relationships might be considered as an important factor in natural recovery from trauma, as well as in intervention. PMID- 26684987 TI - Phenols and lignin: Key players in reducing enzymatic hydrolysis yields of steam pretreated biomass in presence of laccase. AB - Phenols are known as inhibitors for cellulases and fermentative microorganisms in bioethanol production processes. The addition of laccases removes the phenolic compounds and subsequently reduces the lag phase of the fermentative microorganism. However, the application of laccases diminishes glucose release during the enzymatic hydrolysis. In this study a model cellulosic substrate (Sigmacell) together with lignin extract, whole steam-pretreated wheat straw (slurry) and its water insoluble solid fraction (WIS) were subjected to enzymatic hydrolysis to evaluate the effects of laccase treatment in presence of lignin and phenols. The presence of laccase in enzymatic hydrolysis of Sigmacell with lignin extract reduced glucose yield by 37% compared with assays without laccase. Furthermore, this reduction was even more marked in presence of phenols (55% reduction). Interestingly, when hydrolyzing WIS, the addition of phenols coupled with laccase treatment did not show a reduction when compared with only laccase addition. This fact suggests the key role of lignin in the hydrolysis inhibition since in WIS the ratio cellulase per gram of lignin was much lower than in Sigmacell experiments. Finally, the lower cellobiose and xylose recoveries point out that phenolic oligomers formed by laccase oxidation play important roles in the inhibition of endoglucanases, cellobiohydrolases and xylanases. To conclude, the proportion of lignin and the composition of phenols are key players in the inhibition of cellulases when the enzymatic hydrolysis is combined with laccases detoxification. PMID- 26684989 TI - Focus on Children With Behavior Problems. PMID- 26684988 TI - Family Conferences in the Neonatal ICU: Observation of Communication Dynamics and Contributions. AB - OBJECTIVES: Clinicians in the neonatal ICU must engage in clear and compassionate communication with families. Empirical, observational studies of neonatal ICU family conferences are needed to develop counseling best practices and to train clinicians in key communication skills. We devised a pilot study to record and analyze how interdisciplinary neonatal ICU clinicians and parents navigate difficult conversations during neonatal ICU family conferences. DESIGN: We prospectively identified and audiotaped a convenience sample of neonatal ICU family conferences about "difficult news." Conversations were analyzed using the Roter interaction analysis system, a quantitative tool for assessing content and quality of patient-provider communication. SETTING: An urban academic children's medical center with a 45-bed level IV neonatal ICU. SUBJECTS: Neonatal ICU parents and clinicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 19 family conferences that included 31 family members and 23 clinicians. The child's mother was included in all conferences, and a second parent, usually the father, was present in 13 conferences. All but one conference included multiple medical team members. On average, physicians contributed 65% of all dialogue, regardless of who else was present. Over half (56%) of this dialogue involved giving medical information; under 5% of clinician dialogue involved asking questions of the family, and families rarely (5% of dialogue) asked questions. Conversations were longer with the presence of nonphysician clinicians, but this did not increase the amount of dialogue about psychosocial information or increase parent dialogue. CONCLUSIONS: We collected a novel repository of audio-recorded neonatal ICU family meetings that offers insights into discussion content and process. These meetings were heavily focused on biomedical information even when interdisciplinary clinicians were present. Clinicians always talked more than parents, and no one asked many questions. Maximizing the participation of interdisciplinary clinicians in neonatal ICU family meetings may require explicit strategies. Methods to increase family engagement should be targeted. PMID- 26684990 TI - Leadership and Research: Do They Impact Decision Making in Dental Hygiene? PMID- 26684991 TI - Antimicrobial Photodynamic Therapy as an Adjunct to Nonsurgical Periodontal Therapy. AB - The purpose of Linking Research to Clinical Practice is to present evidence based information to clinical dental hygienists so that they can make informed decisions regarding patient treatment and recommendations. Each issue will feature a different topic area of importance to clinical dental hygienists with A BOTTOM LINE to translate the research findings into clinical application. PMID- 26684992 TI - Self-Assessment: A Review of the Literature and Pedagogical Strategies for Its Promotion in Dental Education. AB - PURPOSE: In response to several publications drawing attention to self-assessment and revised Commission on Dental Accreditation standards that state graduates should possess and demonstrate the ability to self-assess, dental hygiene and pre doctoral dental programs find themselves searching for ways in which to incorporate self-assessment practices into the curriculum. Research indicates that students are often not familiar with self-assessment strategies nor are they effective at self-assessment upon entering professional programs. Therefore, students must be taught strategies to self-assess and be given opportunities to practice and refine these skills. Opportunities to develop and demonstrate self assessment skills can be incorporated across the curriculum at the classroom level and at the global level. Both the A.T. Still University Arizona School of Dentistry and Oral Health and the University of Missouri-Kansas City School of Dentistry utilize a capstone portfolio project to incorporate self-assessment throughout the curriculum. By combining artifacts from their dental and dental hygiene school experience with reflective writing essays, students can demonstrate attainment of program competencies. As more faculty members and students become involved and engaged in assessment strategies such as portfolios, they are also gaining a greater appreciation for the value of self-assessment. PMID- 26684993 TI - Sjogren's Syndrome: Oral Manifestations and Treatment, a Dental Perspective. AB - PURPOSE: Sjogren's syndrome is a systemic autoimmune disease affecting approximately 3 million Americans, primarily perimenopausal women. The syndrome is characterized by dysfunction and destruction of exocrine glands leading to oral and ocular manifestations, xerostomia and keratitis sicca. Sjogren's syndrome commonly remains either undiagnosed or is diagnosed years after the onset of symptoms. Diagnosis is based on the concurrent presence of various signs and symptoms of the disease as established by 6 diagnostic standards set by the American European Consensus Group standards: oral symptoms, ocular symptoms, evidence of oral signs, evidence of ocular dryness, evidence of salivary gland involvement with positive Anti-Ro/La autoantibodies and a positive gland biopsy. Currently no definitive test or cure exists; treatment is predominately palliative and supportive. CONCLUSION: With an aging population and heavier reliance on medications and treatments which cause xerostomia, oral health professionals are likely to encounter a higher incidence of xerostomia and Sjogren's syndrome more than ever before. The dental professional must recognize the signs and symptoms of xerostomia, include Sjogren's syndrome in their differential diagnosis, and communicate those findings and concerns to other health care providers, including the primary care physician, rheumatologist and ophthalmologist for evaluation in a timely fashion. This article discusses the dental professional's role in formulating a preventive oral health plan: meticulous oral hygiene instructions, dietary counseling, a complement of chemotherapeutic agents and more frequent recall care to avoid oral complications and improve quality of life. Dental hygienists can help patients understand the wide range of products available to substitute or stimulate salivary flow, prevent or remineralize early carious lesions and relieve candidal and bacterial infections. Ultimately this collaboration of care by the dental and medical professionals will benefit the Sjogren's syndrome patient and lead to better patient outcomes. PMID- 26684994 TI - The Use of Immersive Visualization for the Control of Dental Anxiety During Oral Debridement. AB - PURPOSE: The purpose of this study was to evaluate the effects of Immersive Visualization (IV) eyewear on anxious, adult patients during oral debridement. METHODS: Thirty adult volunteers (n=23 females; n=7 males) were enrolled in the study. Participants were required to be 18 years or older, exhibit at least moderate anxiety (score 9 or higher) on the Corah's Dental Anxiety Scale-Revised (DAS-R), and be generally healthy. Individuals were excluded from participation if they presented with severe dental calculus, periodontal disease, or dental caries, were taking psychotropic drugs, had a history of convulsive disorders, vertigo, or equilibrium disorders, or required antibiotic pre-medication. Subjects received a full mouth oral prophylaxis (supra- and subgingival scaling and selective polishing) by a single experienced dental hygienist. A split mouth design was utilized whereby each subject served as their own control. Subjects were randomly divided into 2 groups: Group A used IV eyewear during the first one half of the appointment (right side of the mouth) and Group B used IV eyewear during the second one-half of the appointment (left side of the mouth). At screening, medical and dental histories were obtained, full mouth oral examinations were performed, and DAS-R was scored to determine eligibility. At baseline, the DAS-R was re-scored to validate anxiety levels. The Calmness Scale was scored pre- and post-IV treatment on a Likert scale ranging from 1 (very calm) to 7 (less calm). At the end of the study, subjects completed a Post IV Opinion survey. Data were entered into Microsoft Excel for Mac 2011 (Microsoft Corporation Version 14.3.5) and analyzed using SAS(r) 9.3 statistical software. RESULTS: Thirty subjects with a mean age of 29.9 years completed the study. Data analysis indicated no statistically significant difference between Group A and B with regard to mean DAS-R anxiety levels at baseline (3.15 and 2.40, respectively), with a p-value of 0.07. Data showed a significant difference when comparing the calmness mean scores within Group A pre- and post-IV treatments (4.66 and 2.93, respectively), with a p-value 0.01. Within Group B the data revealed a statistically significant difference between pre- and post-IV treatments (p<0.01, 4.33 and 2.13, respectively). Both treatment groups experienced a decrease in anxiety levels from pre to post IV treatments. Moreover, combined mean calmness scores of the 30 subjects (Group A and B) expressed in mean standard deviation showed there was a decrease from 4.50+/-1.31 in pre-IV treatment to 2.53+/-1.17 in post-IV treatment. Further investigation of the data showed that there was a significant correlation between calmness and gender; females reported higher levels of anxiety than men before and after IV treatment. CONCLUSION: Results from this study support the use of IV eyewear as an effective technique to reduce anxiety in adults during oral debridement. The use of the IV eyewear was well received by all subjects. The portable, affordable and easy-to-operate IV system makes this technique an appealing approach of reducing dental anxiety. PMID- 26684995 TI - Hearing Difficulties Among Experienced Dental Hygienists: A Survey. AB - PURPOSE: Assess prevalence of self-reported hearing difficulties among experienced dental hygienists who have been practicing for a minimum of 20 years and explore the relationship between hearing difficulties and occupational noise exposure from ultrasonic scalers. METHODS: A 19-item survey was mailed to a random sample of 1,067 dental hygienists who had obtained their California licenses between 1972 and 1992. To estimate the prevalence of hearing difficulty, binomial proportion and associated 95% confidence interval are presented. Logistic regression model of hearing difficulty was used to assess an association with ultrasonic scaler use. RESULTS: Response rate was 35% (n=372/1,067). The prevalence of self-reported hearing difficulty was 40% (95% confidence interval, 35 to 44%). Of the 17% (95% confidence interval, 14 to 21%) of respondents that reported hearing difficulty due to ultrasonic scalers, most (91%) reported that their hearing difficulty was confirmed by an audiologist. Respondents with hearing difficulty due to scalers were 2-times (odds ratio: 2.0, 95% confidence interval, 1.1 to 3.6, p=0.03) more likely to report significantly higher scaler use than those who did not have hearing difficulty after adjusting for age and other potential causes of hearing difficulties. CONCLUSION: The prevalence of hearing difficulty at 40% among dental hygienists with an average age of 56 years was considerably higher than the reported national average at 17% for adults 70 years or older. Long-term noise exposure to dental equipment, such as ultrasonic scalers, may contribute to hearing difficulties among experienced dental hygienists. Ear protection is suggested as a preventive measure while using noisy dental equipment. PMID- 26684996 TI - A Comparison of Technique Errors using Two Radiographic Intra-oral Receptor holding Devices. AB - PURPOSE: Technological advances in intra-oral receptors have resulted in film holding devices that may or may not be interchangeable with photostimulable phosphor receptors. This study evaluated the number and types of technique errors that occurred when using PSP receptors with a standard film-holding device and a dual PSP/film-designed device. METHODS: The Rinn XCP-ORA(r) (Standard) and the Rinn Flip-Ray(r) PA device (Test) were compared using rectangular collimation. DenOptix(r) imaging plates (sizes 1 and 2) were used as receptors. Fourteen periapical (10-size 2 and 4-size 1) projections were exposed per full mouth series on each Dental X-ray Teaching and Training Replica with both devices. Five Dental X-ray Teaching and Training Replicas were exposed by 3 experienced radiographers. Data were analyzed using a paired t-test to determine differences in the performance scores between the 2 devices. Technique errors (receptor placement, vertical angulation, horizontal angulation and cone centering) were reported using frequencies. An experienced evaluator critiqued each projection. RESULTS: A total of 15 full mouth series (210 projections) were taken per device. The mean performance scores per device were 88.4 (standard device) and 88.1 (test device) and were not statistically different (p=0.88). Cone centering errors were the most common error observed in both the standard (36%) and test (43%) devices. Receptor placement errors occurred when using the standard (12%) and test (9%) devices. Vertical and horizontal errors were <2% for both devices. CONCLUSION: Devices designed for use with film may be used interchangeably with photostimulable phosphor receptors. Some difference was noticed between devices regarding error type and occurrence. PMID- 26684997 TI - California Dental Hygiene Educators' Perceptions of an Application of the ADHA Advanced Dental Hygiene Practitioner (ADHP) Model in Medical Settings. AB - PURPOSE: To assess California dental hygiene educators' perceptions of an application of the American Dental Hygienists' Association's (ADHA) advanced dental hygiene practitioner model (ADHP) in medical settings where the advanced dental hygiene practitioner collaborates in medical settings with other health professionals to meet clients' oral health needs. METHODS: In 2014, 30 directors of California dental hygiene programs were contacted to participate in and distribute an online survey to their faculty. In order to capture non respondents, 2 follow-up e-mails were sent. Descriptive analysis and cross tabulations were analyzed using the online survey software program, QualtricsTM. RESULTS: The educator response rate was 18% (70/387). Nearly 90% of respondents supported the proposed application of the ADHA ADHP model and believed it would increase access to care and reduce oral health disparities. They also agreed with most of the proposed services, target populations and workplace settings. Slightly over half believed a master's degree was the appropriate educational level needed. CONCLUSION: Among California dental hygiene educators responding to this survey, there was strong support for the proposed application of the ADHA model in medical settings. More research is needed among a larger sample of dental hygiene educators and clinicians, as well as among other health professionals such as physicians, nurses and dentists. PMID- 26684998 TI - Oral Health Care of Vietnamese Adolescents: A Qualitative Study of Perceptions and Practices. AB - PURPOSE: To explore the oral health perceptions and practices of Vietnamese adolescents 13 to 17 years old in San Jose, Calif. METHODS: A purposeful sample of 10 Vietnamese parents with adolescent children were recruited at a Temple in San Jose, Calif. After gaining parental consent and adolescent assent, Vietnamese adolescents participated in an audio-taped, 20 to 30 minute, individual, semi structured interview in English to explore their perceptions about oral health. Interview data were transcribed verbatim. All statements related to each question were identified, and similar statements were grouped into categories. RESULTS: Ten adolescents participated in the study. All reported tooth appearance as the most important reason for oral care, and that oral health, diet and general health were related. All were concerned about dental pain. Of the respondents, 9 believed that having good teeth would give them more confidence, and help them find jobs and romantic partners, while 2 did not follow recommended oral hygiene routines or recognize early signs of disease. Seven participants favored U.S. dentists over Vietnamese dentists. Frequently reported barriers to seeking dental care were fear of dental treatment (n=7) and inability to pay for dental care (n=6). CONCLUSION: When educating Vietnamese adolescents, dental hygienists need to highlight availability of pain control, encourage better performance of personal oral hygiene and recommend dental clinics with sliding fee scales to low income families. This approach to oral health education may enhance dental health and seeking of regular dental visits. PMID- 26685001 TI - Prediction of the post-dilution hematocrit during cardiopulmonary bypass. Are new formulas needed? AB - OBJECTIVES: Predicting the post-dilution hematocrit is an important tool to avoid preventable anemia or unnecessary transfusion. Simplified empirical formulas currently used for such a prediction may lead to large errors. We aimed to improve the accuracy of these formulas by a better estimation of the dilution volume and the patient circulatory blood volume. METHODS: We compared the estimation accuracy of two formulas, using fixed (formula A) versus estimated (formula D) dilution volume and patient circulatory blood volume for 100 cardiac interventions. The difference between predicted and measured HctT1 was considered as "good" if less than 0.5%, "moderate" between 0.5 and 2% and "poor" if higher than 2%. The influence of the body mass index (BMI) on patient blood volume estimation was explored by categorized groups' comparison. RESULTS: The mean difference between predicted and measured HctT1 differed significantly between formulas A and D. Formula A didn't differ from HctT1 (p=0.19, IC95% [-0.89 0.18]), but a significant and higher underestimation was observed in the BMI?25 group compared to the other BMI groups (p<0.001). Formula D overestimated HctT1 (p<0.001, IC95% [1.01-1.93]) without a difference between the BMI groups. No difference was observed in their overall proportions of good (11 vs 10%), moderate (44 vs 46%) and poor predictions (47 vs 44%) (p=0.117). CONCLUSIONS: Formulas used for post-dilution hematocrit prediction lead to major estimation errors and a risk of inadequate transfusion practices. Estimations performed by experienced clinicians could not minimize these biases in all clinical cases as significant errors remain, with potential clinical impact. No estimation formula should be used as a hard tool for transfusing patients, but rather as a guide to predicting the probability of transfusion requirement. PMID- 26685002 TI - Impact of carbon dioxide tension during cardiopulmonary bypass on tissue perfusion in neonates undergoing cardiac surgery using autologous umbilical cord blood. AB - OBJECTIVE: Previously, we reported that the oxyhemoglobin dissociation curve is shifted leftward in patients who receive autologous umbilical cord blood (UCB) during neonatal open heart surgery. In this study, we assessed whether allowing the pCO2 to rise during hypothermic cardiopulmonary perfusion would shift the curve back to the right and improve tissue oxygenation. METHODS: The study population included prenatally diagnosed patients with transposition of the great arteries. The study cohort was divided into two groups and consisted of early patients originally managed with lower pCO2 levels (Group I, n=42, 2009-12) and later patients subsequently managed with higher pCO2 levels (Group II, n=38, 2012 14). RESULTS: Patients received similar volumes of collected autologous UCB (Group I, 80 ml; Group II, 75ml, p=0.207) with a similar mean level of HbF during CPB (Group I, 90+/-8%; Group II, 87+/-9%, p=0.310). Higher levels of pCO2 during CPB (Group I, 31 mmHg; Group II, 37 mmHg, p=0.011) resulted in a rightward shift of the oxyhemoglobin dissociation curve (increased p50O2) (Group I, 19.5+/-3.4 mmHg; Group II, 22.5+/-2.2 mmHg, p=0.011). The use of a higher pCO2 strategy was associated with decreased serum lactate during CPB (Group I, 4.7+/-2 mmol/l; Group II, 2.8+/-1.4 mmol/l, p=0.001), decreased duration of mechanical ventilation (Group I, 46h; Group II, 22h, p<0.001) and decreased of length of intensive care unit (ICU) stay (Group I, 7.6+/-2.6, Group II, 5.6+/-2.2, p=0.003) CONCLUSIONS: A higher pCO2 during CPB in neonates who underwent open heart surgery using UCB resulted in a rightward shift of the oxyhemoglobin dissociation curve and was associated with improved serum lactate levels. PMID- 26685004 TI - Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. AB - BACKGROUND: In severe asthmatics with persistent airway eosinophilia, blockade of interleukin-5 has significant steroid-sparing effects and attenuates blood and sputum eosinophilia. The contribution of local maturational processes of progenitors within the airways relative to the recruitment of mature cells from the peripheral circulation to the development of airway eosinophilia is not known. We hypothesize that local eosinophilopoiesis may be the predominant process that drives persistent airway eosinophilia and corticosteroid requirement in severe asthmatics. OBJECTIVES: In a cross-sectional study, the number and growth potential of eosinophil-lineage-committed progenitors (EoP) were assayed in 21 severe eosinophilic asthmatics, 19 mild asthmatics, eight COPD patients and eight normal subjects. The effect of anti-IL-5 treatment on mature eosinophils and EoP numbers was made in severe eosinophilic asthmatics who participated in a randomized clinical trial of mepolizumab (substudy of a larger GSK sponsored global phase III trial, MEA115575) where subjects received mepolizumab (100 mg, n = 9) or placebo (n = 8), as six monthly subcutaneous injections. RESULTS: Mature eosinophil and EoP numbers were significantly greater in the sputum of severe asthmatics compared with all other subject groups. In colony-forming assays, EoP from blood of severe asthmatics demonstrated a greater response to IL-5 than mild asthmatics. Treatment of severe asthmatics with mepolizumab significantly attenuated blood eosinophils and increased EoP numbers consistent with blockade of systemic eosinophilopoiesis. There was however no significant treatment effect on mature eosinophils, sputum EoP numbers or the prednisone maintenance dose. CONCLUSIONS AND CLINICAL RELEVANCE: Patients with severe eosinophilic asthma have an exaggerated eosinophilopoeitic process in their airways. Treatment with 100 mg subcutaneous mepolizumab significantly attenuated systemic differentiation of eosinophils, but did not suppress local airway eosinophil differentiation to mature cells. Targeting IL-5-driven eosinophil differentiation locally within the lung maybe of relevance for optimal control of airway eosinophilia and asthma. PMID- 26685003 TI - Minimal tumour burden in haematological diseases: a step forward with quantitative assessment of Bence-Jones in nephelometry? PMID- 26685005 TI - Experimental pain impairs recognition memory irrespective of pain predictability. AB - BACKGROUND: Pain is hardwired to signal threat and tissue damage and therefore automatically attracts attention to initiate withdrawal or defensive behaviour. This well-known interruptive function of pain interferes with cognitive functioning and is modulated by bottom-up and top-down variables. Here, we applied predictable or unpredictable painful heat stimuli simultaneously to the presentation of neutral images to investigate (I) whether the predictability of pain modulated its effect on the encoding of images (episodic memory) and (II) whether subjects remember that certain images have been previously presented with pain (source memory). METHODS: Twenty-four healthy subjects performed a categorization task in which 80 images had to be categorized into living or non living objects. We compared the processing and encoding of these images during cued and non-cued pain trials as well as cued and non-cued pain-free trials. Effects on recognition performance and source memory for pain were immediately tested using a surprise recognition task. RESULTS: Painful thermal stimulation impaired recognition accuracy (d', recollection, familiarity). This negative effect of pain was positively correlated with the individual expectation of pain interference and the attentional avoidance of pain-related words. However, the interruptive effect of pain was not modulated by the predictability of pain. Source memory for painful stimulation was at chance level, indicating that subjects did not explicitly remember that images had been paired with pain. CONCLUSIONS: Targeting negative expectations and a maladaptive attentional bias for pain-related material might help reducing frequently reported pain-induced cognitive impairments. PMID- 26685006 TI - Late-stage alpha-synuclein accumulation in TNWT-61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging. AB - Diffusion kurtosis imaging (DKI) by measuring non-Gaussian diffusion allows an accurate estimation of the distribution of water molecule displacement and may correctly characterize microstructural brain changes caused by neurodegeneration. The aim of this study was to evaluate the ability of DKI to detect changes induced by alpha-synuclein (alpha-syn) accumulation in alpha-syn over-expressing transgenic mice (TNWT-61) in both gray matter (GM) and white matter (WM) using region of interest (ROI) and tract-based spatial statistics analyses, respectively, and to explore the relationship between alpha-syn accumulation and DKI metrics in our regions of interest. Fourteen-month-old TNWT-61 mice and wild type (WT) littermates underwent in vivo DKI scanning using the Bruker Avance 9.4 Tesla magnetic resonance imaging system. ROI analysis in the GM regions substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus and tract-based spatial statistics analysis in WM were performed. Immunohistochemistry for alpha-syn was performed in TNWT-61 mice and correlated with DKI findings. We found increased kurtosis and decreased diffusivity values in GM regions such as the thalamus and sensorimotor cortex, and in WM regions such as the external and internal capsule, mamillothalamic tract, anterior commissure, cingulum, and corpus callosum in TNWT-61 mice as compared to WT mice. Furthermore, we report for the first time that alpha-syn accumulation is positively correlated with kurtosis and negatively correlated with diffusivity in the thalamus. The study provides evidence of an association between the amount of alpha-syn and the magnitude of DKI metric changes in the ROIs, with the potential of improving the clinical diagnosis of Parkinson's disease. We propose diffusion kurtosis imaging as a sensitive method for detecting human alpha-synuclein accumulation-induced changes in brain tissue, which may be reflective of Parkinson disease stage. Boxplots show the averaged mean kurtosis (orange) and mean diffusivity (blue) under the results of the analysis (*p < 0.05) in brains of wild-type (WT) and alpha-synuclein over-expressing (TNWT-61) mice. This approach might represent a novel biomarker for the early diagnosis of Parkinson's disease. Read the Editorial Highlight for this article on page 1117. PMID- 26685009 TI - miRNA 206 and miRNA 574-5p are highly expression in coronary artery disease. AB - Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide. Innovative diagnostic biomarkers are a pressing need for this disease. miRNAs profiling is an innovative method of identifying biomarkers for many diseases and could be proven as a powerful tool in the diagnosis and treatment of CAD. We performed miRNA microarray analysis from the plasma of three CAD patients and three healthy controls. Subsequently, we performed quantitative real-time PCR (qRT-PCR) analysis of miRNA expression in plasma of another 67 CAD patients and 67 healthy controls. We identified two miRNAs (miR-206 and miR-574 5p) that were significantly up-regulated in CAD patients as compared with healthy controls (P<0.05). The receiver operating characteristic (ROC) curves indicated these two miRNAs had great potential to provide sensitive and specific diagnostic value for CAD. PMID- 26685011 TI - Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis. PMID- 26685010 TI - A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. AB - BACKGROUND: Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. PATIENTS AND METHODS: Baseline data were available from 762 patients treated with abiraterone-prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. RESULTS: Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin <=4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen deprivation therapy to start of treatment <=36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 +/- 0.014. The model was validated by the external dataset (n = 286). CONCLUSION: This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. TRIAL REGISTRATION NUMBERS: NCT00638690. PMID- 26685012 TI - Photoresponsive Molecular Memory Films Composed of Sequentially Assembled Heterolayers Containing Ruthenium Complexes. AB - Photoresponsive molecular memory films were fabricated by a layer-by-layer (LbL) assembling of two dinuclear Ru complexes with tetrapodal phosphonate anchors, containing either 2,3,5,6-tetra(2-pyridyl)pyrazine or 1,2,4,5-tetra(2 pyridyl)benzene as a bridging ligand (Ru-NP and Ru-CP, respectively), using zirconium phosphonate to link the layers. Various types of multilayer homo- and heterostructures were constructed. In the multilayer heterofilms such as ITO||(Ru NP)m |(Ru-CP)n , the difference in redox potentials between Ru-NP and Ru-CP layers was approximately 0.7 V, which induced a potential gradient determined by the sequence of the layers. In the ITO||(Ru-NP)m |(Ru-CP)n multilayer heterofilms, the direct electron transfer (ET) from the outer Ru-CP layers to the ITO were observed to be blocked for m>2, and charge trapping in the outer Ru-CP layers became evident from the appearance of an intervalence charge transfer (IVCT) band at 1140 nm from the formation of the mixed-valent state of Ru-CP units, resulting from the reductive ET mediation of the inner Ru-NP layers. Therefore, the charging/discharging ("1"and "0") states in the outer Ru-CP layers could be addressed and interconverted by applying potential pulses between -0.5 and +0.7 V. The two states could be read out by the direction of the photocurrent (anodic or cathodic). The molecular heterolayer films thus represent a typical example of a photoresponsive memory device; that is, the writing process may be achieved by the applied potential (-0.5 or +0.7 V), while the readout process is achieved by measuring the direction of the photocurrent (anodic or cathodic). Sequence-sensitive multilayer heterofilms, using redox-active complexes as building blocks, thus demonstrate great potential for the design of molecular functional devices. PMID- 26685013 TI - Advances in mechanisms and modifications for rendering yeast thermotolerance. AB - Thermotolerant Saccharomyces cerevisiae is widely regarded as an attractive strain with which to accomplish the coupling of enzyme saccharification, ethanol fermentation and ethanol distillation in non-grain fuel bioethanol fermentation systems, and it has many advantages for increasing the ethanol yield and reducing production costs. This review provided an overview of the yeast heat-resistant mechanisms from six aspects, including gene expression responses, heat shock proteins, trehalose, ATPase, the ubiquitin-proteasome pathway and heat-induced antioxidant defenses. Innovative methods, such as random and rational strategies for improving yeast thermotolerance, were further discussed, and several special cases were provided. To rationally engineer thermotolerance in yeast, the advances in employing heat-resistant mechanisms of thermophiles were particularly discussed. By designing and constructing heat-resistant devices consists of heat resistant parts from thermophiles to yeast, a superior thermotolerance of S. cerevisiae has been achieved, providing a new system with important applications for research regarding the improvement of the robustness of microbes. PMID- 26685014 TI - Discovery and characterization of a second extremely thermostable (+)-gamma lactamase from Sulfolobus solfataricus P2. AB - A thermostable formamidase from the hyperthermophilic archaeon Sulfolobus solfataricus P2 was revealed to be a novel, thermostable (+)-gamma-lactamase. This (+)-gamma-lactamase (Sso2810) is composed of only 318 amino acid residues, in contrast to a previously reported (+)-gamma-lactamase (Sso2122) with 504 amino acid residues from the same strain. Herein, we demonstrate that a single strain may contain diverse (+)-gamma-lactamases. The gene of this thermostable (+)-gamma lactamase was cloned, functionally expressed in Escherichia coli BL21 and purified by a simple yet effective heat treatment method. Sso2810 was biochemically characterized and compared to Sso2122, with phylogenetic analysis indicating different evolutionary histories for the two encoding genes. This newly found thermostable enzyme shows promising properties for industrial applications; specifically, it could be used for the production of chirally pure (-)-gamma-lactam for the synthesis of well-known carbocyclic nucleoside antiretroviral agents like Abacavir and Peramivir. The chiral product of the enzyme was purified to >99% enantiomeric excess. PMID- 26685015 TI - Probing neural cell behaviors through micro-/nano-patterned chitosan substrates. AB - In this study, we describe the development of surface-modified chitosan substrates to examine topographically related Neuro-2a cell behaviors. Different functional groups can be modified on chitosan surfaces to probe Neuro-2a cell morphology. To prepare chitosan substrates with micro/nano-scaled features, we demonstrated an easy-to-handle method that combined photolithography, inductively coupled plasma reactive ion etching, Ag nanoparticle-assisted etching, and solution casting. The results show that Neuro-2a cells preferred to adhere to a flat chitosan surface rather than a nanotextured chitosan surface as evidenced by greater immobilization and differentiation, suggesting that surface topography is crucial for neural patterning. In addition, we developed chitosan substrates with different geometric patterns and flat region depth; this allowed us to re-arrange or re-pattern Neuro-2a cell colonies at desired locations. We found that a polarity-induced micropattern provided the most suitable surface pattern for promoting neural network formation on a chitosan substrate. The cellular polarity of single Neuro-2a cell spreading correlated to a diamond-like geometry and neurite outgrowth was induced from the corners toward the grooves of the structures. This study provide greater insight into neurobiology, including neurotransmitter screening, electrophysiological stimulation platforms, and biomedical engineering. PMID- 26685016 TI - Minimally Invasive Cardiac Surgery Using a 3D High-Definition Endoscopic System. AB - We describe a minimally invasive heart surgery application of the EinsteinVision 2.0 3D high-definition endoscopic system (Aesculap AG, Tuttlingen, Germany) in an 81-year-old man with severe tricuspid valve insufficiency. Fourteen years ago, he underwent a Ross procedure followed by a DDD pacemaker implantation 4 years later for tachy-brady-syndrome. His biventricular function was normal. We recommended minimally invasive tricuspid valve repair. The application of the aformentioned endoscopic system was simple, and the impressive 3D depth view offered an easy and precise manipulation through a minimal thoracotomy incision, avoiding the need for a rib spreading retractor. PMID- 26685017 TI - Carbon nanotube-CdS core-shell nanowires with tunable and high-efficiency microwave absorption at elevated temperature. AB - Tuning microwave absorption to meet the harsh requirement of thermal environments is a great challenge. Three kinds of nanowires, including multi-walled carbon nanotubes (MWCNTs) coated with CdS nanocrystals (CdS-MWCNTs), and MWCNTs coated with different-thickness CdS sheaths, have been synthesized through mild solution process synthesis. The influence of CdS amount, external temperature, loading concentration and sample thickness on the absorption performance were studied. The composite loading with 6 vol.% CdS-MWCNTs shows the best absorption of -47 dB at 473 K with a thickness of 2.6 mm in the temperature range of 323-573 K and X band. The effective bandwidth covers the full X band in 323-473 K for RL <= -20 dB and reaches 2.0 GHz at 473 K for RL <= -20 dB. The enhanced absorption ability of CdS-MWCNTs arises from the effective impedance matching, benefiting from abundant interfacial polarization from the added CdS nanocrystals and the changeable dielectric property at elevated temperature. The results indicate that the CdS-MWCNT is a promising functional material for high temperature microwave absorption. PMID- 26685018 TI - A chronic opioid therapy dose reduction policy in primary care. AB - BACKGROUND: High-dose opioids prescribed for the treatment of chronic pain have been associated with increased risk of opioid overdose. Health systems and states have responded by developing opioid dose limitation policies. Little is known about how these policies affect prescribing practices or characteristics of patients who respond best to opioid tapers from high-dose opioids. METHODS: We conducted a retrospective cohort study to evaluate change in total opioid dose after the implementation of a provider education intervention and a 120 mg morphine equivalents per day (MED) opioid dose limitation policy in one academic primary care clinic. We compared opioid prescriptions 1 year before and 1 year after the intervention. We used univariate and multivariate logistic regression to assess which patient characteristics predicted opioid dose reduction from high opioid dose. RESULTS: Out of a total of 516 patients prescribed chronic opioid therapy, 116 patients (22%) were prescribed high-dose opioid therapy (>120 mg MED). After policy adoption, the average daily dose of opioids declined by 64 mg MED (95% confidence interval [CI]: 32-96; P < .001) and 41 patients (37%) on high dose opioids tapered their doses below 120 mg MED (Tapered to Safer Dose group). In multivariate analyses, female sex was the only significant association with dose taper; female patients were less likely to taper to a safer dose (adjusted odds ratio [aOR] = 0.28, 95% CI: 0.11-0.70). CONCLUSIONS: A combined intervention of education and a practice policy that limits opioid doses for patients prescribed chronic opioid therapy may be an important component of system-level strategies to reduce opioid misuse and overdose; it may also help identify patients suitable for medication-assisted treatment for opioid use disorder. Specific strategies may be needed to assist women with opioid dose tapers. PMID- 26685019 TI - Risk of psychological distress in parents of preterm children in the first year: evidence from the UK Millennium Cohort Study. AB - OBJECTIVE: To assess whether the parents of babies born preterm (PT; <37 weeks completed gestation) are at excess risk of psychological distress (PD) at 9 months postpartum, and to explore the influence of the degree of prematurity. DESIGN AND PARTICIPANTS: Data were drawn from the UK Millennium Cohort Study, a nationally representative prospective cohort of babies born in 2000-2002. 12,100 families with complete data available for both parents at recruitment (9 months postpartum) are included. EXPOSURE AND OUTCOME: Mothers report of gestational age at birth (in weeks) was grouped into: very PT (<32 weeks), moderately PT (32-33 weeks), late PT (34-36 weeks), early term (37-38 weeks), full-term (39-41 weeks), post-term (42 weeks). PD was assessed using a modified Rutter Malaise Inventory, a validated instrument that has been used in both men and women to assess levels of anxiety and distress. RESULTS: Overall, 7% of families reported a PT birth; 12.1% of mothers and 8.9% of fathers showed signs of PD at 9 months postpartum. The mothers of very PT infants had an increased risk of PD, compared with the mothers of full-term babies (unadjusted OR 2.10 (1.30 to 3.39; adjusted OR 1.66 (1.02 to 2.69)). Mothers of moderate or late PT babies had no apparent increased risk of PD. However, mothers of early term babies also showed a small excess risk of PD (adjusted OR 1.16 (0.99 to 1.36)). Unadjusted analysis suggested a doubling in the risk of PD in fathers of very and moderately PT babies, compared with fathers of full-term babies, which remains statistically significant after adjustment in the moderately PT group (adjusted OR1.98 (1.20 to 3.29)). CONCLUSIONS: The parents of very PT children are at an increased risk of PD at 9 months postpartum, and mothers of children born at early term also see an elevated risk compared with mothers of full-term babies. PMID- 26685020 TI - Systematic review of the evidence on the effectiveness of sexual and reproductive health interventions in humanitarian crises. AB - OBJECTIVES: This systematic review aims to evaluate evidence on the effectiveness of sexual and reproductive health (SRH) interventions delivered in humanitarian crises. SETTING: Crisis affected low-income or middle-income countries. PARTICIPANTS: Crisis-affected populations in low-income or middle-income countries. METHOD: Peer-reviewed and grey literature sources were systematically searched for relevant papers detailing interventions from 1 January 1980 until the search date on 30 April 2013. Data from included studies were then extracted, and the papers' quality evaluated using criteria based on modified STROBE and CONSORT checklists. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes include, but are not limited to, changes in morbidity, mortality, sexually transmitted infection (STI) diagnosis or gender-based violence. Secondary outcomes include, but are not limited to, reported condom use or skilled attendance at birth. Primary outputs include, but are not limited to, condoms distributed or education courses taught. RESULTS: Of 7149 returned citations, 15 studies met the inclusion criteria. Only one randomised controlled trial was identified. The remaining observational studies were of moderate quality, demonstrating limited use of controls and inadequate attempts to address bias. Evidence of effectiveness was available for the following interventions: impregnated bed nets for pregnant women, subsidised refugee healthcare, female community health workers, and tiered community reproductive health services. CONCLUSIONS: The limited evidence base for SRH interventions highlights the need for improved research on the effectiveness of public health interventions in humanitarian crises. While interventions proven efficacious in stable settings are being used in humanitarian efforts, more evidence is required to demonstrate the effectiveness of delivering and scaling-up such interventions in humanitarian crises. PMID- 26685022 TI - Higher incidence of rheumatoid arthritis in patients with symptomatic osteoarthritis or osteoarthritis-related surgery: a nationwide, population-based, case-control study in Taiwan. AB - OBJECTIVES: To investigate the risk of incident rheumatoid arthritis in patients with symptomatic osteoarthritis or osteoarthritis-related surgery using a nationwide health claims database. DESIGN: A nationwide, population-based, case control study. SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: A total of 1147 patients (aged 20-100 years) with rheumatoid arthritis and 5735 controls who were frequency-matched for sex, 10-year age interval and year of catastrophic illness certificate application date (index year) were identified. MAIN OUTCOME MEASURE: All participants were retrospectively traced, up to 14 years prior to their index year, for diagnosis of osteoarthritis or osteoarthritis-related surgery. Multivariate logistic regression analyses were conducted to quantify the association between rheumatoid arthritis and osteoarthritis. RESULTS: The risks of rheumatoid arthritis were significantly higher in patients with symptomatic osteoarthritis (adjusted OR=5.24, p<0.001) and osteoarthritis-related surgery (adjusted OR=2.27, p<0.001). CONCLUSIONS: This large nationwide, population-based, case-control study showed a higher risk of rheumatoid arthritis in Taiwanese patients with symptomatic osteoarthritis. Our findings were consistent with the hypothesis that osteoarthritis might be a triggering factor of rheumatoid arthritis in environment-sensitised and genetically susceptible individuals. PMID- 26685023 TI - Lung cancer treatment rates and the role of the lung cancer nurse specialist: a qualitative study. AB - OBJECTIVES: This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. SETTING: 4 Hospital NHS Foundation Trusts in England. DESIGN: A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. PARTICIPANTS: Four LCNSs, comprised the 'cases'. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took part in a group interview and 60 lung cancer multidisciplinary team (MDT) members and coordinators were observed in the MDT meeting. RESULTS: The LCNS is crucial within the MDT and can act as a catalyst to patient access to treatment. The study identified the clinical activity (assessment, managing symptoms, psychological support and information provision) and role characteristics that can facilitate treatment access. These characteristics are the LCNS's presence across the patient pathway, acting as the 'hub' of the MDT, maintaining a holistic patient focus and working to an advanced level of practice. The findings indicate how factors may have a cumulative impact on treatment access. CONCLUSIONS: If UK patient with lung cancer survival rates are to improve in line with comparable countries, we need to employ every advantage. This study demonstrates how the LCNS role may open doors to positive patient outcomes, including treatment. Further research is required to explore patients' experiences, decision-making and attitudes to treatment. PMID- 26685021 TI - Investigation of the relationship between patient empowerment and glycaemic control in patients with type 2 diabetes: a cross-sectional analysis. AB - OBJECTIVE: To determine whether there is an association between patient empowerment and diabetes management in terms of the primary outcomes of metabolic control as measured by glycaemic control (glycated haemoglobin, HbA1c), high density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC) and triglycerides. DESIGN: Retrospective cross-sectional analysis conducted in 2012. SETTING: Data from Diabetes Federation of Ireland from participants enrolled in the Community Orientated Diabetes Education (CODE) Programme. PARTICIPANTS: 569 patients diagnosed with type 2 diabetes. EXPOSURES: Patient empowerment levels, as measured by the Diabetes Empowerment Scale-Short Form. Additional information collected included patients' gender, age, body mass index (BMI), smoking status and number of years with diabetes. OUTCOME MEASURES: HbA1c, HDL, LDL, TC and triglycerides values. RESULTS: Partial correlation analyses failed to show any statistically significant relationship between patient empowerment and glycaemic control or other diabetes management variables (HbA1c, p=0.32; HDL, p=0.95; LDL, p=0.77; TC, p=0.49; triglycerides, p=0.77). Logistic regression analysis confirmed that patient empowerment score was not a significant predictor of level of glycaemic control. Time since diagnosis of diabetes was associated with increased HbA1c levels. Age and gender were significant predictors of HDL and LDL levels, while gender and age were associated with changes in TC and triglycerides levels, respectively. CONCLUSIONS: No significant association was found between patient empowerment levels and other measures of diabetes control in this study. Further research into the short-term and long-term outcomes of the empowerment model, at different levels of disease management, and across different settings, is required to evaluate its value in the management of patients with diabetes. PMID- 26685024 TI - Effect of obesity on functional outcomes at 6 months post-stroke among elderly Koreans: a prospective multicentre study. AB - OBJECTIVES: We examined whether obesity based on body mass index (BMI) was a predictor of functional independence measure (FIM) at 6 months after ischaemic stroke onset while adjusting for stroke risk factors and covariates and stratifying by age group. DESIGN: This is an interim report of the Korean Stroke Cohort for Functioning and Rehabilitation that was designed as a nested case study within a nationwide hospital-based cohort. SETTING: We identified all patients who were admitted to nine representative hospitals in Korea from 2012 until 2014 under a diagnosis of acute first-ever ischaemic stroke. The hospitals were selected from the metropolitan district, mid-sized cities and a small-sized city. PARTICIPANTS: The sample included 2057 patients with acute ischaemic stroke who were at least 18 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: We divided participants into two age levels (<65 and >= 65 years). Participants were classified into five groups according to their baseline BMI at admission: underweight (BMI<18.5), normal (18.5 <= BMI<23), overweight (23 <= BMI<25), obese (25 <= BMI<30) and extremely obese (30 <= BMI). RESULTS: The proportion of patients who were aged >= 65 years was 55.0%. The proportions of underweight, normal, overweight, obese and extremely obese patients were 2.6%, 24.3%, 29.6%, 37.2% and 6.3%, respectively, in the <65 years group and 5.5%, 34.5%, 27.9%, 28.8% and 3.3%, respectively, in the >= 65 years group. In a multiple linear regression, the 6-month FIM after stroke in the elderly group was significantly associated with being extremely obese (7.95, p<0.05) after adjusting for confounding variables. In the <65 years group, the 6-month FIM was not associated with any weight category. CONCLUSIONS: This nationwide hospital-based cohort study showed that extreme obesity is a predictor of a good 6-month FIM, especially in patients with ischaemic stroke who are at least 65 years of age. PMID- 26685025 TI - Metabolic syndrome and health-related behaviours associated with pre-oral cancerous lesions among adults aged 20-80 years in Yunlin County, Taiwan: a cross sectional study. AB - OBJECTIVES: To explore the associations of health-related behaviours, metabolic syndrome and risk factors in adults with pre-oral cancerous (POC) lesions in rural, disadvantaged communities with a high prevalence of oral cancer. DESIGN: A cross-sectional observational study. SETTING: Community-based health survey in the western coastal area of Yunlin County, Taiwan. PARTICIPANTS: 5161 adult residents participated in this study. OUTCOME MEASURES: Assessed parameters included oral leukoplakia, oral submucous fibrosis, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure and waist circumference. Statistical analyses included descriptive statistics, chi(2) tests and multivariate binary logistic regression. RESULTS: A high percentage of participants were found to have metabolic syndrome (40%) and POC lesions (7.3%). Participants with POC lesions tended to be male (p<0.001), betel nut chewers (p<0.001) and cigarette smokers (p<0.001); have a low level of education (p<0.001); seldom undergo dental check-ups (p<0.01); irregularly participate in physical activity (p<0.01) and have metabolic syndrome (p<0.01). CONCLUSIONS: Although male sex and disadvantaged socioeconomic status are non-modifiable factors associated with POC and metabolic syndrome in adults, several factors, notably health behaviours, are modifiable. Clinicians can reduce the incidence and consequences of POC by developing programmes for early detection, encouraging regular dental check-ups, and initiating individualised, health-promoting behaviour modification programmes for reducing risky behaviours associated with oral cancer. PMID- 26685026 TI - Social distribution of diabetes, hypertension and related risk factors in Barbados: a cross-sectional study. AB - OBJECTIVE: To describe the distribution of diabetes, hypertension and related behavioural and biological risk factors in adults in Barbados by gender, education and occupation. DESIGN: Multistage probability sampling was used to select a representative sample of the adult population (>= 25 years). Participants were interviewed using standard questionnaires, underwent anthropometric and blood pressure measurements, and provided fasting blood for glucose and cholesterol measurements. Standard WHO definitions were used. Data were weighted for sampling and non-response, and were age and sex standardised to the 2010 Barbados population. Weighted prevalence estimates were calculated, and prevalence ratios were calculated for behavioural and biological risk factors by demographic and socioeconomic group. RESULTS: Study response rate was 55.0%, with 764 women, 470 men. Prevalence of obesity was 33.8% (95% CI 30.7% to 37.1%); hypertension 40.6% (95% CI 36.5% to 44.9%); and diabetes 18.7% (95% CI 16.2% to 21.4%). Compared with women, men were less likely to be obese (prevalence ratio 0.5; 95% CI 0.4 to 0.7), or physically inactive (0.5; 0.4 to 0.6), but more likely to smoke tobacco (4.1; 2.5 to 6.7) and consume large amounts of alcohol in a single episode (4.6; 2.7 to 7.6). Both diabetes (0.83; 0.65 to 1.05) and hypertension (0.89; 0.79 to 1.02) were lower in men, but not significantly so. In women, higher educational level was related to higher fruit and vegetable intake, more physical activity, less diabetes and less hypercholesterolaemia (p 0.01 0.04). In men, higher education was related only to less smoking (p 0.04). Differences by occupation were limited to smoking in men and hypercholesterolaemia in women. CONCLUSIONS: In this developing country population, sex appears to be a much stronger determinant of behavioural risk factors, as well as obesity and its related risks, than education or occupation. These findings have implications for meeting the commitments made in the 2011 Rio Political Declaration, to eliminate health inequities. PMID- 26685027 TI - Incidence of childhood pneumonia: facility-based surveillance estimate compared to measured incidence in a South African birth cohort study. AB - BACKGROUND: Pneumonia is the leading cause of childhood mortality and a major contributor to childhood morbidity, but accurate measurement of pneumonia incidence is challenging. We compared pneumonia incidence using a facility-based surveillance system to estimates from a cohort study conducted contemporaneously in the same community in Cape Town, South Africa. METHODS: A surveillance system was developed in six public sector primary care clinics and in a regional referral hospital, to detect childhood pneumonia cases. Nurses recorded all children presenting to facilities who met WHO case definitions of pneumonia, and hospital records were reviewed. Estimates of pneumonia incidence and severity were compared with incidence rates based on active surveillance in the Drakenstein Child Health Study. RESULTS: From June 2012 until September 2013, the surveillance system detected 306 pneumonia episodes in children under 1 year of age, an incidence of 0.20 episodes/child-year (e/cy) (95% CI 0.17 to 0.22 e/cy). The incidence in the cohort study from the same period was 0.27 e/cy (95% CI 0.23 to 0.32 e/cy). Pneumonia incidence in the surveillance system was almost 30% lower than in the birth cohort; incidence rate ratio 0.72 (95% CI 0.58 to 0.89). In the surveillance system, 18% were severe pneumonia cases, compared to 23% in the birth cohort, rate ratio 0.81 (95% CI 0.55 to 1.18). CONCLUSIONS: In this setting, facility-based pneumonia surveillance detected fewer cases of pneumonia, and fewer severe cases, compared to the corresponding cohort study. Facility pneumonia surveillance using data collected by local healthcare workers provides a useful estimate of the epidemiology of childhood pneumonia but may underestimate incidence and severity. PMID- 26685028 TI - Past and recent abuse is associated with early cessation of breast feeding: results from a large prospective cohort in Norway. AB - OBJECTIVE: Breast feeding provides a wide range of health benefits for both infants and mothers. Few studies have examined the impact of past and recent abuse of women on breastfeeding behaviour. The aims of our study were to examine whether exposure to past and recent emotional, sexual or physical abuse was associated with early breastfeeding cessation, and to assess whether a potential association differed for known and unknown perpetrators. DESIGN: Prospective cohort study. SETTING: Norway, years 1999-2006. PARTICIPANTS: 53,934 mothers participated in the Norwegian Mother and Child Cohort Study. We included mothers with singleton pregnancy who had responded to three questionnaires (weeks 18 and 30 in pregnancy, and 6 months postpartum) and had answered minimum one of the abuse questions in week 30. MAIN OUTCOME MEASURE: ORs were estimated by binary logistic regression with cessation of any (all) breast feeding before 4 months as the outcome, and abuse including subcategories of abuse, as the exposure. RESULTS: Nearly all women initiated breast feeding, but 12.1% ceased any breast feeding before 4 months and 38.9% ceased full breast feeding before 4 months, but continued partial breast feeding. Overall, 19% of the women reported any adult abuse and 18% reported any child abuse. The highest risk of any breast feeding cessation before 4 months was seen in women exposed to three types of adult abuse (emotional, sexual or physical), with adjusted OR being 1.47 (95% CI 1.23 to 1.76) compared with no abuse. Recent abuse and exposure from known perpetrator resulted in nearly 40% and 30% increased risk, respectively. The OR of any breast feeding cessation for women exposed to any child abuse was 1.41 (95% CI 1.32 to 1.50) compared with no abuse in childhood. CONCLUSIONS: Past and recent abuse of women is strongly associated with early cessation of breast feeding. Abused mothers comprise a key group to target for extra support and breastfeeding assistance. PMID- 26685029 TI - Is there a relationship between surgical case volume and mortality in congenital heart disease services? A rapid evidence review. AB - OBJECTIVE: To identify and synthesise the evidence on the relationship between surgical volume and patient outcomes for adults and children with congenital heart disease. DESIGN: Evidence synthesis of interventional and observational studies. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library and Web of Science (2009-2014) and citation searching, reference lists and recommendations from stakeholders (2003-2014) were used to identify evidence. STUDY SELECTION: Quantitative observational and interventional studies with information on volume of surgical procedures and patient outcomes were included. RESULTS: 31 of the 34 papers identified (91.2%) included only paediatric patients. 25 (73.5%) investigated the relationship between volume and mortality, 7 (20.6%) mortality and other outcomes and 2 (5.9%) non-mortality outcomes only. 88.2% were from the US, 97% were multicentre studies and all were retrospective observational studies. 20 studies (58.8%) included all congenital heart disease conditions and 14 (41.2%) single conditions or procedures. No UK studies were identified. Most studies showed a relationship between volume and outcome but this relationship was not consistent. The relationship was stronger for single complex conditions or procedures. We found limited evidence about the impact of volume on non mortality outcomes. A mixed picture emerged revealing a range of factors, in addition to volume, that influence outcome including condition severity, individual centre and surgeon effects and clinical advances over time. CONCLUSIONS: The heterogeneity of findings from observational studies suggests that, while a relationship between volume and outcome exists, this is unlikely to be a simple, independent and directly causal relationship. The effect of volume on outcome relative to the effect of other, as yet undetermined, health system factors remains a complex and unresolved research question. PMID- 26685030 TI - Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections. AB - INTRODUCTION: The management of intra-articular chondral defects in the knee remains a challenge. Inadequate healing in areas of weight bearing leads to impairment in load transmission and these defects predispose to later development of osteoarthritis. Surgical management of full thickness chondral defects include arthroscopic microfracture and when appropriate autologous chondrocyte implantation. This latter method however is technically challenging, and may not offer significant improvement over microfracture. Preclinical and limited clinical trials have indicated the capacity of mesenchymal stem cells to influence chondral repair. The aim of this paper is to describe the methodology of a pilot randomised controlled trial comparing arthroscopic microfracture alone for isolated knee chondral defects versus arthroscopic microfracture combined with postoperative autologous adipose derived mesenchymal stem cell injections. METHODS AND ANALYSIS: A pilot single-centre randomised controlled trial is proposed. 40 participants aged 18-50 years, with isolated femoral condyle chondral defects and awaiting planned arthroscopic microfracture will be randomly allocated to a control group (receiving no additional treatment) or treatment group (receiving postoperative adipose derived mesenchymal stem cell treatment). Primary outcome measures will include MRI assessment of cartilage volume and defects and the Knee Injury and Osteoarthritis Outcome Score. Secondary outcomes will include further MRI assessment of bone marrow lesions, bone area and T2 cartilage mapping, a 0-10 Numerical Pain Rating Scale, a Global Impression of Change score and a treatment satisfaction scale. Adverse events and cointerventions will be recorded. Initial outcome follow-up for publication of results will be at 12 months. Further annual follow-up to assess long-term differences between the two group will occur. ETHICS AND DISSEMINATION: This trial has received prospective ethics approval through the Latrobe University Human Research Ethics Committee. Dissemination of outcome data is planned through both national and international conferences and formal publication in a peer reviewed journal. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register (ANZCTR Trial ID: ACTRN12614000812695). PMID- 26685031 TI - Occupation and risk of sudden death in a United States community: a case-control analysis. AB - OBJECTIVE: Work environment is said to influence cardiovascular risk. We assessed whether nature of occupation affects risk of sudden cardiac death (SCD) in the general population. METHODS: In the ongoing, prospective Oregon Sudden Unexpected Death Study (catchment population 1 million), working-age SCD cases (18-65 years) were compared with controls who died from any cause. Usual occupation obtained from death certificates was classified using the US Census Bureau standard occupational classification descriptions and categorised as white collar, blue collar or homemaker. Odds ratio (OR) for SCD by occupation category was obtained and clinical profile of SCD cases was compared by occupation type. RESULTS: Among SCD cases (n=646; 74% male) compared to controls (n=622; 73.6% male), the proportion of white collar workers was higher among male SCD cases (52.7% vs 43.7%; p=0.01); the difference in females was smaller (59.5% vs 55%; p=0.62). Adjusting for race and smoking status, male white collar workers had a higher risk of SCD compared to blue collar workers (OR=1.67, (1.26 to 2.23), p<0.001). A similar, non-significant trend was observed among females (OR 1.49 (0.81 to 2.75); p=0.20). White collar SCD cases were less likely to be current smokers (34.7% vs 45.3%, p=0.008), drug misusers (13.1% vs 18.5%) or have diabetes (21.4% vs 28.2%, both p=0.07) compared to blue collar workers. Other cardiac risk factors were similar. CONCLUSIONS: A white collar occupation was associated with increased risk of SCD, when compared to blue collar occupations. Since differences in conventional risk factors did not explain this elevated risk, work related behavioural and psychosocial stressors warrant a closer evaluation. PMID- 26685033 TI - Support for infants and young people with sight loss: a qualitative study of sight impairment certification and referral to education and social care services. AB - OBJECTIVES: To examine the experience of infants, children and their parents, the role of ophthalmologists and other health, social care and education professionals in the certification and registration processes and examine the relationship between certification and referrals and pathways to support. DESIGN: Qualitative study. SETTING: Telephone interviews with health and, social care professionals, qualified teachers of children and young people with vision impairment (QTVIs) and parents of infants/children in England. PARTICIPANTS: 52 health, social care and education professionals who are part of the certification or registration process. 26 parents of infants and children with vision impairment. RESULTS: Referrals to education do not require a Certificate of Vision Impairment (CVI); however, the majority of parents received support from education and social services only after an offer of the CVI, which was often dependent on having a formal diagnosis. Parents stated they wanted support sooner, particularly parents of children with additional complex needs who experienced longer delays. Areas with multidisciplinary teams and support roles such as eye clinic liaison officers (ECLOs) appeared to have more reliable referral pathways. CONCLUSIONS: For infants and children with vision impairment, there should be a consistent mechanism for triggering education and social care support even with uncertainty about diagnosis and/or prognosis. All professionals involved in the certification and registration processes (ophthalmologists, optometrists, ECLOs, orthoptists, social workers, QTVIs) can better communicate the value and benefits of certification and registration. PMID- 26685032 TI - Impulsivity-focused group intervention to reduce binge eating episodes in patients with binge eating disorder: study protocol of the randomised controlled IMPULS trial. AB - INTRODUCTION: The core symptom of binge eating disorder (BED) is recurrent binge eating that is accompanied by a sense of loss of control. BED is frequently associated with obesity, one of the main public health challenges today. Experimental studies deliver evidence that general trait impulsivity and disorder specific food-related impulsivity constitute risk factors for BED. Cognitive behavioural treatment (CBT) is deemed to be the most effective intervention concerning BED. We developed a group intervention based on CBT and especially focusing on impulsivity. We hypothesise that such an impulsivity-focused group intervention is able to increase control over impulsive eating behaviour, that is, reduce binge eating episodes, further eating pathology and impulsivity. Body weight might also be influenced in the long term. METHODS AND ANALYSIS: The present randomised controlled trial investigates the feasibility, acceptance and efficacy of this impulsivity-focused group intervention in patients with BED. We compare 39 patients with BED in the experimental group to 39 patients with BED in the control group at three appointments: before and after the group intervention and in a 3-month follow-up. Patients with BED in the experimental group receive 8 weekly sessions of the impulsivity-focused group intervention with 5-6 patients per group. Patients with BED in the control group receive no group intervention. The primary outcome is the binge eating frequency over the past 4 weeks. Secondary outcomes comprise further eating pathology, general impulsivity and food-related impulsivity assessed by eye tracking methodology, and body weight. Additionally, we assess binge eating and other impulsive behaviour weekly in process analyses during the time period of the group intervention. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of the medical faculty of Eberhard Karls University Tubingen and the University Hospital Tubingen. Data are monitored by the Centre of Clinical Studies, University Hospital Tubingen. TRIAL REGISTRATION NUMBER: German Clinical Trials Register, DRKS00007689, 14/01/2015, version from 11/06/2015, pre-results. PMID- 26685034 TI - Impact of a combined community and primary care prevention strategy on all-cause and cardiovascular mortality: a cohort analysis based on 1 million person-years of follow-up in Vasterbotten County, Sweden, during 1990-2006. AB - OBJECTIVE: To evaluate the impact of the Vasterbotten Intervention Programme (VIP) by comparing all eligible individuals (target group impact) according to the intention-to-treat principle and VIP participants with the general Swedish population. DESIGN: Dynamic cohort study. SETTING/PARTICIPANTS: All individuals aged 40, 50 or 60 years, residing in Vasterbotten County, Sweden, between 1990 and 2006 (N=101,918) were followed from their first opportunity to participate in the VIP until age 75, study end point or prior death. INTERVENTION: The VIP is a systematic, long-term, county-wide cardiovascular disease (CVD) intervention that is performed within the primary healthcare setting and combines individual and population approaches. The core component is a health dialogue based on a physical examination and a comprehensive questionnaire at the ages of 40, 50 and 60 years. PRIMARY OUTCOMES: All-cause and CVD mortality. RESULTS: For the target group, there were 5646 deaths observed over 1,054,607 person-years. Compared to Sweden at large, the standardised all-cause mortality ratio was 90.6% (95% CI 88.2% to 93.0%): for women 87.9% (95% CI 84.1% to 91.7%) and for men 92.2% (95% CI 89.2% to 95.3%). For CVD, the ratio was 95.0% (95% CI 90.7% to 99.4%): for women 90.4% (95% CI 82.6% to 98.7%) and for men 96.8% (95% CI 91.7 to 102.0). For participants, subject to further impact as well as selection, when compared to Sweden at large, the standardised all-cause mortality ratio was 66.3% (95% CI 63.7% to 69.0%), whereas the CVD ratio was 68.9% (95% CI 64.2% to 73.9%). For the target group as well as for the participants, standardised mortality ratios for all-cause mortality were reduced within all educational strata. CONCLUSIONS: The study suggests that the VIP model of CVD prevention is able to impact on all cause and cardiovascular mortality when evaluated according to the intention-to treat principle. PMID- 26685035 TI - Epidemiological features of alcohol use in rural India: a population-based cross sectional study. AB - OBJECTIVES: We sought to estimate the proportion of adults in Sehore District, India, who consumed alcohol, and the proportion who had behaviours consistent with alcohol use disorders (AUDs), using the Alcohol Use Disorders Identification Test (AUDIT). Among men who drank, we identified individual-level, household level and community-level factors associated with AUDIT scores. Men with AUDs (AUDIT score >= 8) reported on whether and where they had sought treatment, and about alcohol-related internal stigma. DESIGN: Population-based cross-sectional study. SETTING: Rural villages and urban wards in Sehore District, Madhya Pradesh, India. PARTICIPANTS: n=3220 adult (>= 18 years of age) residents of Sehore District. PRIMARY OUTCOME MEASURE: Score on the AUDIT. RESULTS: Nearly one in four men (23.8%) had consumed alcohol in the past 12 months, while few (0.6%) women were consumers. Among drinkers, 33.2% (95% CI 28.6% to 38.1%) had AUDIT scores consistent with hazardous drinking, 3.3% (95% CI 2.1% to 5.1%) with harmful drinking and 5.5% (95% CI 3.8% to 8.0%) with dependent drinking. We observed that AUDIT scores varied widely by village (intraclass correlation=0.052). Among men who had recently consumed alcohol, AUDIT scores were positively associated with depression, having at least one child, high quality housing, urban residence, tobacco use and disability. AUDIT scores were negatively associated with land ownership, out-of-pocket healthcare expenditure and participation in the national employment programme. While 49.2% of men with AUDs felt embarrassed by their problems with alcohol, only 2.8% had sought treatment in the past 12 months. CONCLUSIONS: A need exists for effectively identifying and treating adults with AUDs. Health promotion services, informed by commonly-expressed stigmatised beliefs held among those affected by AUDs and which are targeted at the most affected communities, may be an effective step in closing the treatment gap. PMID- 26685036 TI - Perceived quality of HIV treatment and care services in Wolaita Zone of southern Ethiopia: a cross-sectional study. AB - OBJECTIVE: To investigate the levels and factors affecting the perceived quality of HIV/AIDS treatment and care services. DESIGN: A cross-sectional study. SETTING: The study was conducted in Wolaita Zone of southern Ethiopia in one hospital and five health centres providing antiretroviral therapy (ART) and pre ART. PARTICIPANTS: 481 persons infected with HIV on outpatient care, 408 (83.8%) on ART and 73 (16.2%) on pre-ART care. RESULTS: 324 (71.4%) of the participants perceived the quality of HIV care as 'good', while 130 (28.6%) stated that it was 'not good'; 219 (46.2%) and 255 (53.8%) were satisfied and not satisfied with the services, respectively. In the multivariate analysis, a unit increase in the doctors subscale of multidimensional health locus of control-form c score resulted in a 1.27 (1.04 to 1.55) increase in the odds of perceived good quality of care (p<0.05). Similarly, a unit increase in the responsiveness, perceived financial fairness, and perceived transportation convenience scores was associated with a 1.03 (1.01 to 1.05) (p<0.05), 1.08 (1.05 to 1.15) (p<0.01), and 1.07 (1.05 to 1.18) (p<0.05) increase in the odds of perceived good quality of HIV care, respectively. In terms of client satisfaction with services, a 1 km increase in the distance from health facilities, and unemployment were associated with a 4.64 (2.61 to 8.25) (p<0.001), 1.02 (1.01 to 1.04) (p<0.05) and 2.23 (1.30 to 4.54) (p<0.01) times, respectively, increase in the perceived quality of HIV treatment and care services. CONCLUSIONS: The majority of the participants reported perceptions of good quality HIV care and satisfaction with the services. Satisfaction with services; responsiveness; health locus of control; perceived financial fairness; perceived transportation convenience; employment status; and distance from the health facility were predictors of the perceived quality of HIV care. Thus, improving quality of HIV treatment services may require addressing the above factors. PMID- 26685037 TI - Hfq: a multifaceted RNA chaperone involved in virulence. AB - Hfq has emerged in recent years as a master regulator of gene expression in bacteria, mainly due to its ability to mediate the interaction of small noncoding RNAs with their mRNA targets, including those related to virulence in Gram negative bacteria. In this work, we review current knowledge on the involvement of Hfq in the regulation of virulence traits related to secretion systems, alternative sigma factors, outer membrane proteins, polysaccharides and iron metabolism. Recent data from transcriptomics and proteomics studies performed for major pathogens are included. We also summarize and correlate current knowledge on how Hfq protein impacts pathogenicity of bacterial pathogens. PMID- 26685038 TI - The Bactericidal Effect of 2780 and 940 nm Laser Irradiation on Enterococcus faecalis in Bovine Root Dentin Slices of Different Thicknesses. AB - OBJECTIVE: The aim of this in vitro study was to investigate the antibacterial effect of the dual wavelength (2780 nm Er,Cr:YSGG and 940 nm diode) laser in elimination of Enterococcus faecalis in comparison with a 2780 nm Er,Cr:YSGG laser alone. BACKGROUND DATA: Various laser wavelengths have been introduced as an adjunct in root canal treatment because of laser's bactericidal effect. MATERIALS AND METHODS: Seventy- five slices of dentin with thicknesses of 300, 500, and 1000 MUm (n = 25 each) obtained from caries-free bovine teeth were inoculated with 1 MUL of E. faecalis suspension [1.67 * 10(7) colony-forming units (CFU)] and divided randomly into three groups: (A) samples indirectly irradiated with power settings of 1.06 W, 50 Hz, and 50 MUs for Er,Cr:YSGG laser; (B) samples indirectly irradiated with Er,Cr:YSGG laser with the same power settings as group A and simultaneously with a 940 nm diode laser of 0.51 W in pulsed mode; and five samples from each thickness that were chosen as an unirradiated control group (Co). After irradiation, the CFU of E. faecalis were counted and the bacterial reduction was analyzed using Kruskal-Wallis nonparametric and post-hoc Dunnett tests. RESULTS: There were statistical differences between groups A and B compared with the control group over all the three dentin slice thicknesses (p < 0.001). However, there was no statistical difference between groups A and B in killing of E. faecalis on 500 MUm dentin slices. There were significantly more viable bacteria in group A than in group B in 300 and 1000 MUm dentin slices (p < 0.01). CONCLUSIONS: The results of this in vitro study showed that the dual wavelength laser system obtained a significantly higher bactericidal effect on E. faecalis than Er,Cr:YSGG laser, reaching a depth of 1000 MUm of dentin. PMID- 26685039 TI - Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury. AB - Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 MUL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases. PMID- 26685049 TI - An Easy and Useful Noninvasive Score Based on alpha-1-acid Glycoprotein and C Reactive Protein for Diagnosis of Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection. AB - This study aimed to evaluate the diagnostic value of alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP) and develop a predictive score to improve the diagnosis of hepatocellular carcinoma (HCC). AGP and CRP were measured in serum of 53 HCC patients and 20 liver cirrhosis (LC) patients, in addition to 15 healthy individuals. Area under receiver-operating characteristic curves (AUCs) was used to create a predictive score comprising AGP, CRP, alpha fetoprotein, and albumin. The diagnostic performances of score was determined and compared with AFP alone for the diagnosis of HCC. The combination of AGP, albumin, CRP, and AFP had AUC 0.92 and sensitivity 85% which was higher than AFP alone. The odds ratio of having HCC was 8.4 for AGP, 5.8 for CRP, 12.5 for AFP and 6.5 for albumin. Our score predicted HCC with an OR of 50.6 for HCC. The AUC of score in HCC with single tumor, absent vascular invasion and CLIP score (0-1) were 0.9, 0.9, 0.82, respectively, compared with 0.71, 0.71, 0.68, respectively, for AFP. In conclusion, a non-invasive and simple score based on AGP, CRP, AFP, and albumin could improve the accuracy of HCC diagnosis. PMID- 26685050 TI - Eldad Melamed 1942-2015: Ave atque--A memorial. PMID- 26685051 TI - Catalysts Encapsulated in Molecular Machines. AB - Smart catalysts offer the control of chemical processes and sequences of transformations, and catalysts with unique catalytic behavior can afford chiral products or promote successive polymerization. To meet advanced demands, the key to constructing smart catalysts is to incorporate traditional catalytic functional groups with trigger-induced factors. Molecular machines with dynamic properties and particular topological structures have typical stimulus-responsive features. In recent years, scientists have made efforts to utilize molecular machines (molecular switches, rotaxanes, motors, etc.) as scaffolds to develop smart catalysts. This Minireview focuses on the achievements of developing catalysts encapsulated in molecular machines and their remarkable specialties. This strategy is believed to provide more potential applications in switchable reactions, asymmetric synthesis, and processive catalysis. PMID- 26685052 TI - Dowling-Degos disease co-presenting with Darier disease. AB - We present a case of a patient with long-standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling-Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail-bed discolouration, and V-shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli-Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient. PMID- 26685053 TI - Velocity Control of 180 degrees Domain Walls in Ferroelectric Thin Films by Electrode Modification. AB - The velocity of individual 180 degrees domain walls in thin ferroelectric films of PbZr0.1Ti0.9O3 is strongly dependent on the thickness of the top Pt electrode made by electron-beam induced deposition (EBID). We show that when the thickness is varied in the range <100 nm the domain wall velocity is seen to change by 7 orders of magnitude. We attribute this huge range of velocities to the similarly large range of resistivities for the EBID Pt electrode as extrapolated from four point probe measurements. The domain wall motion is governed by the supply of charges to the domain wall, determined by the top electrode resistivity, and which is described using a modified Stefan Problem model. This has significant implications for the feasibility of ferroelectric domain wall nanoelectronics, wherein the speed of operation will be limited by the maximum velocity of the propagating domain wall front. Furthermore, by introducing sections of either modified thickness or width along the length of a "line" electrode, the domain wall velocity can be changed at these locations, opening up possibilities for dynamic regimes. PMID- 26685055 TI - Respiratory Muscle Strength, Sound Pressure Level, and Vocal Acoustic Parameters and Waist Circumference of Children With Different Nutritional Status. AB - OBJECTIVE: Relate respiratory muscle strength (RMS), sound pressure (SP) level, and vocal acoustic parameters to the abdominal circumference (AC) and nutritional status of children. STUDY DESIGN: This is a cross-sectional study. METHODS: Eighty-two school children aged between 8 and 10 years, grouped by nutritional states (eutrophic, overweight, or obese) and AC percentile (<=25, 25-75, and >=75), were included in the study. Evaluations of maximal inspiratory pressure (IPmax) and maximal expiratory pressure (EPmax) were conducted using the manometer and SP and acoustic parameters through the Multi-Dimensional Voice Program Advanced (KayPENTAX, Montvale, New Jersey). RESULTS: There were significant differences (P < 0.05) in the EPmax of children with AC between the 25th and 75th percentiles (72.4) and those less than or equal to the 25th percentile (61.9) and in the SP of those greater than or equal to the 75th percentile (73.4) and less than or equal to the 25th percentile (66.6). The IPmax, EPmax, SP levels, and acoustic variables were not different in relation to the nutritional states of the children. There was a strong and positive correlation between the coefficient of amplitude perturbations (shimmer), the harmonics-to-noise ratio and the variation of the fundamental frequency, respectively, 0.79 and 0.71. CONCLUSIONS: RMS and acoustic voice characteristics in children do not appear to be influenced by nutritional states, and respiratory pressure does not interfere with acoustic voice characteristics. However, localized fat, represented by the AC, alters the EPmax and the SP, each of which increases as the AC increases. PMID- 26685054 TI - Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6. AB - Tumor necrosis factor-stimulated gene-6 (TSG-6) is a hyaluronan (HA)-binding protein that is essential for stabilizing and remodeling the extracellular matrix (ECM) during ovulation and inflammatory disease processes such as arthritis. The Link module, one of the domains of TSG-6, is responsible for binding hyaluronan and other glycosaminoglycans found in the ECM. In this study, we used a well defined chondroitin sulfate (CS) hexasaccharide (DeltaC444S) to determine the structure of the Link module, in solution, in its chondroitin sulfate-bound state. A variety of nuclear magnetic resonance techniques were employed, including chemical shift perturbation, residual dipolar couplings (RDCs), nuclear Overhauser effects, spin relaxation measurements, and paramagnetic relaxation enhancements from a spin-labeled analogue of DeltaC444S. The binding site for DeltaC444S on the Link module overlapped with that of HA. Surprisingly, DeltaC444S binding induced dimerization of the Link module (as confirmed by analytical ultracentrifugation), and a second weak binding site that partially overlapped with a previously identified heparin site was detected. A dimer model was generated using chemical shift perturbations and RDCs as restraints in the docking program HADDOCK. We postulate that the molecular cross-linking enhanced by the multiple binding modes of the Link module might be critical for remodeling the ECM during inflammation/ovulation and might contribute to other functions of TSG-6. PMID- 26685056 TI - Paediatrician and Caregiver Awareness of Cryptosporidiosis and Giardiasis in Children: US Survey Responses. AB - There appears to be no published information concerning the awareness and knowledge about diarrhoea caused by Cryptosporidium spp. or Giardia lamblia among US paediatricians and caregivers of young children. Two concurrent, separate surveys were conducted among paediatricians and caregivers (~1000 respondents in each survey) of children ages 1-12 years concerning their knowledge, perceptions and attitudes in the diagnosis and treatment of parasitic diarrhoea. Awareness of parasite-induced diarrhoea was low for specific aspects among both paediatricians and caregivers. Educational efforts to improve awareness on the appropriate clinical presentation, management and treatment of cryptosporidiosis and giardiasis in children with persistent diarrhoea should be undertaken. PMID- 26685057 TI - Inventory of Novel Animal Models Addressing Etiology of Preeclampsia in the Development of New Therapeutic/Intervention Opportunities. AB - Preeclampsia is a pregnancy-related disease afflicting 3-7% of pregnancies worldwide and leads to maternal and infant morbidity and mortality. The disease is of placental origin and is commonly described as a disease of two stages. A variety of preeclampsia animal models have been proposed, but all of them have limitations in fully recapitulating the human disease. Based on the research question at hand, different or multiple models might be suitable. Multiple animal models in combination with in vitro or ex vivo studies on human placenta together offer a synergistic platform to further our understanding of the etiology of preeclampsia and potential therapeutic interventions. The described animal models of preeclampsia divide into four categories (i) spontaneous, (ii) surgically induced, (iii) pharmacologically/substance induced, and (iv) transgenic. This review aims at providing an inventory of novel models addressing etiology of the disease and or therapeutic/intervention opportunities. PMID- 26685058 TI - Effects of the endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae) parasitism, venom, and calyx fluid on cellular and humoral immunity of its host Chilo suppressalis (Lepidoptera: Crambidae) larvae. AB - The larval endoparasitoid Cotesia chilonis injects venom and bracoviruses into its host Chilo suppressalis during oviposition. Here we study the effects of the polydnavirus (PDV)-carrying endoparasitoid C. chilonis (Hymenoptera: Braconidae) parasitism, venom and calyx fluid on host cellular and humoral immunity, specifically hemocyte composition, cellular spreading, encapsulation and melanization. Total hemocyte counts (THCs) were higher in parasitized larvae than in unparasitized larvae in the late stages following parasitization. While both plasmatocyte and granulocyte fractions and hemocyte mortality did not differ between parasitized and unparasitized hosts, in vitro spreading behavior of hemocytes was inhibited significantly by parasitism throughout the course of parasitoid development. C. chilonis parasitism suppressed the encapsulation response and melanization in the early stages. Venom alone did not alter cellular immune responses, including effects on THCs, mortality, hemocyte composition, cell spreading and encapsulation, but venom did inhibit humoral immunity by reducing melanization within 6h after injection. In contrast to venom, calyx fluid had a significant effect on cell spreading, encapsulation and melanization from 6h after injection. Dose-response injection studies indicated the effects of venom and calyx fluid synergized, showing a stronger and more persistent reduction in immune system responses than the effect of either injected alone. PMID- 26685059 TI - The fungicide Pristine(r) inhibits mitochondrial function in vitro but not flight metabolic rates in honey bees. AB - Honey bees and other pollinators are exposed to fungicides that act by inhibiting fungal mitochondria. Here we test whether a common fungicide (Pristine(r)) inhibits the function of mitochondria of honeybees, and whether consumption of ecologically-realistic concentrations can cause negative effects on the mitochondria of flight muscles, or the capability for flight, as judged by CO2 emission rates and thorax temperatures during flight. Direct exposure of mitochondria to Pristine(r) levels above 5 ppm strongly inhibited mitochondrial oxidation rates in vitro. However, bees that consumed pollen containing Pristine(r) at ecologically-realistic concentrations (~ 1 ppm) had normal flight CO2 emission rates and thorax temperatures. Mitochondria isolated from the flight muscles of the Pristine(r)-consuming bees had higher state 3 oxygen consumption rates than control bees, suggesting that possibly Pristine(r)-consumption caused compensatory changes in mitochondria. It is likely that the lack of a strong functional effect of Pristine(r)-consumption on flight performance and the in vitro function of flight muscle mitochondria results from maintenance of Pristine(r) levels in the flight muscles at much lower levels than occur in the food, probably due to metabolism and detoxification. As Pristine(r) has been shown to negatively affect feeding rates and protein digestion of honey bees, it is plausible that Pristine(r) consumption negatively affects gut wall function (where mitochondria may be exposed to higher concentrations of Pristine(r)). PMID- 26685060 TI - Metabolic profiling for the identification of Huntington biomarkers by on-line solid-phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools. AB - In this work, an untargeted metabolomic approach based on sensitive analysis by on-line solid-phase extraction capillary electrophoresis mass spectrometry (SPE CE-MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild-type (wt) and HD (R6/1) mice of different ages (8, 12, and 30 weeks), were analyzed by C18 -SPE CE-MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the multiple full scan MS datasets. This strategy permitted the resolution of a large number of metabolites being characterized by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow-up the HD progression. The intracellular signaling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors, and changed expression of neurotransmitters. PMID- 26685061 TI - Treatment of endosulfan contaminated water with in vitro plant cell cultures. AB - Endosulfan is a Persistent Organic Pollutant insecticide still used in many countries. It is commercially available as mixtures of two diastereomers, alpha- and beta-endosulfan, known as technical grade endosulfan (TGE). A laboratory model based on the use of axenic plant cell cultures to study the removal and metabolization of both isomers from contaminated water matrixes was established. No differences were recorded in the removal of the two individual isomers with the two tested endemic plants, Grindelia pulchella and Tessaria absinthioides. Undifferentiated cultures of both plant species were very efficient to lower endosulfan concentration in spiked solutions. Metabolic fate of TGE was evaluated by analyzing the time course of endosulfan metabolites accumulation in both plant biomass and bioremediation media. While in G. pulchella we only detected endosulfan sulfate, in T. absinthioides the non-toxic endosulfan alcohol was the main metabolite at 48h, giving the possibility of designing phytoremediation approaches. PMID- 26685062 TI - Preparation of ultrafine magnetic biochar and activated carbon for pharmaceutical adsorption and subsequent degradation by ball milling. AB - Ball milling was used to prepare two ultrafine magnetic biochar/Fe3O4 and activated carbon (AC)/Fe3O4 hybrid materials targeted for use in pharmaceutical removal by adsorption and mechanochemical degradation of pharmaceutical compounds. Both hybrid adsorbents prepared after 2h milling exhibited high removal of carbamazepine (CBZ), and were easily separated magnetically. These adsorbents exhibited fast adsorption of CBZ and tetracycline (TC) in the initial 1h. The biochar/Fe3O4 had a maximum adsorption capacity of 62.7mg/g for CBZ and 94.2mg/g for TC, while values obtained for AC/Fe3O4 were 135.1mg/g for CBZ and 45.3mg/g for TC respectively when data were fitted using the Langmuir expression. Solution pH values slightly affected the sorption of TC on the adsorbents, while CBZ sorption was almost pH-independent. The spent adsorbents with adsorbed CBZ and TC were milled to degrade the adsorbed pollutants. The adsorbed TC itself was over 97% degraded after 3h of milling, while about half of adsorbed CBZ were remained. The addition of quartz sand was found to improve the mechanochemical degradation of CBZ on biochar/Fe3O4, and its degradation percent was up to 98.4% at the dose of 0.3g quarts sand/g adsorbent. This research provided an easy method to prepare ultrafine magnetic adsorbents for the effective removal of typical pharmaceuticals from water or wastewater and degrade them using ball milling. PMID- 26685063 TI - Chrysotile asbestos detoxification with a combined treatment of oxalic acid and silicates producing amorphous silica and biomaterial. AB - This study was primarily imposed by the ever increasing need for detoxification of asbestos and asbestos containing materials (ACM), with potential application onsite. The present work investigates potential detoxification of pure chrysotile (Chr) asbestos via a combined treatment of oxalic acid dihydrate (Oxac) (Eta2C2Omicron4.2Eta2Omicron) with silicates, such as tetraethoxysilane (TEOS) (SiH20C8O4) and pure water glass (WG) (potassium silicate) (K2SiO3). These reagents used in the experimental procedure, do not cause adverse effects on the environment and are cost effective. The results of FTIR, XRD, optical and scanning microscopy coupled with EDS analyses indicated that all of the applied treatments destructed the Chr structure and yielded silica of amorphous phase and the biomaterial glushinskite from the Oxac reacted with brucite [Mg(OH)2] layer. Each of the proposed formulations can be applied for the detoxification of asbestos, according to priorities related to the specific products of the recovery treatment. Therefore, Oxac acid leaching followed by the TEOS addition is preferred in cases of glushinskite recovery; TEOS treatment of asbestos with subsequent Oxac addition produced amorphous silica production; finally Oxac acid leaching followed by WG encapsulated the asbestos fibers and can be used in cases of onsite asbestos and ACM detoxification. PMID- 26685064 TI - Efficient transport of Am(III) from nitric acid medium using a new conformationally constrained (N,N,N',N'-tetra-2-ethylhexyl)7 oxabicyclo[2.2.1]heptane-2,3-dicarboxamide across a supported liquid membrane. AB - Am(III) is one of the most hazardous radionuclide present in nuclear fuel cycle. A new conformationally constrained diamide, (N,N,N',N'-tetra-2-ethylhexyl)7 oxabicyclo[2.2.1]heptane-2,3-dicarboxamide (OBDA) was studied for Am(III) transport from HNO3 medium across a Supported Liquid Membrane. Transport rate was observed to be significantly fast with ~95% transport of Am(III) within 1h using 0.1M OBDA in the presence of 15% isodecyl alcohol (IDA)/n-dodecane as carrier. The mechanism of transport was investigated by studying various parameters like feed HNO3/NaNO3 concentration, OBDA concentration in the membrane, membrane pore size, membrane thickness etc. From these studies, the mechanism of transport was found to be diffusion controlled with diffusion co-efficient value of 5.1*10( 6)cm(2)/s. The membrane was found to be highly selective for tri- and tetra valent actinides, and trivalent lanthanides. OBDA based membrane was found to be stable for at least for ten consecutive cycles of operation. PMID- 26685065 TI - Degradation of trichloroethylene by hydrodechlorination using formic acid as hydrogen source over supported Pd catalysts. AB - An advanced method for the degradation of trichloroethylene (TCE) over Pd/MCM-41 catalysts through a hydrogen-transfer was investigated. Formic acid (FA) was used instead of gaseous H2 as the hydrogen resource. As a model H-carrier compound, FA has proven to yield less by-products and second-hand pollution during the reaction. Several factors have been studied, including: the property of catalyst supports, Pd loading and size, temperature, initial concentrations of FA and TCE (potential impact on the reaction rates of TCE degradation), and FA decomposition. The intrinsic kinetics for TCE degradation were measured, while the apparent activation energies and the reaction orders with respect to TCE and FA were calculated through power law models. On the basis of kinetics, we assumed a plausible reaction pathway for TCE degradation in which the catalytic degradation of TCE is most likely the rate-determining step for this reaction. PMID- 26685066 TI - A comparison of the Miller laryngoscope versus the prototype neonatal offset blade laryngoscope in a manikin. AB - Laryngoscope blades used to intubate newborn babies are relatively bulky and frequently exert high pressure on the upper jaw. We tested a prototype neonatal offset-blade laryngoscope (NOBL) developed to overcome these limitations. Our aims were to compare the pressure on the upper jaw exerted by a size 0 Miller laryngoscope and the NOBL on a neonatal manikin, as well as the time taken to intubate the trachea and the area of view of the larynx. Twenty healthcare professionals with more than five years of experience in neonatal intensive care took part; the findings were assessed using pressure-sensitive film and photographs. High-pressure indentation occurred in 17 (85%) attempts using the Miller versus 1 (5%) using the NOBL (p = 0.0001). The median (IQR [range]) pressure exerted with the Miller laryngoscope was 455 (350-526 [75-650]) kPa vs 80 (0-133 [0-195]) kPa with the NOBL (p < 0.0001). The area of pressure exerted with the Miller laryngoscope was 68 (32-82 [0-110]) mm(2) vs 8 (0-23 [0-40]) mm(2) with the NOBL (p < 0.0001). The time to intubate was 8.3 (7.3-10.1[4-19]) s for the Miller and 8.0 (5.6-9.6 [4-13.5]) s for the NOBL (p < 0.0001). The area of view blocked by the Miller laryngoscope was 38% of the oral orifice versus 12% with the NOBL. We conclude that the NOBL significantly reduced undesired pressure on the upper jaw during tracheal intubation and improved the view of the larynx compared with a conventional laryngoscope. PMID- 26685067 TI - Current mass spectrometry approaches and challenges for the bioanalysis of traditional Chinese medicines. AB - Traditional Chinese medicines (TCMs) are gaining more and more attentions all over the world. The focus of TCMs researches were gradually shifted from chemical research to the combination study of chemical and life sciences. However, obtaining precise information of TCMs process in vivo or in vitro is still a bottleneck in bioanalysis of TCMs for their chemical composition complexity. This paper reviewed the recent analytical methods especially mass spectrometry technology in the bioanalysis of TCMs, and data processing techniques in the qualitative and quantitative analyses of metabolite of TCMs. Additionally, the difficulties encountered in the analyzing biological samples in TCMs and the solutions to these problems have been mentioned. PMID- 26685069 TI - Sensitivity and specificity of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: A single-center study in Japan. AB - OBJECTIVE: To compare the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium. BACKGROUND: These tools have not been tested in a specialized cardio-surgical ICU. METHODS: Sensitivities and specificities of each tool were assessed in a cardio-surgical ICU in Japan by two trained nurses independently. Results were compared with delirium diagnosed by psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. RESULTS: There were 110 daily, paired assessments in 31 patients. The CAM-ICU showed 38% sensitivity and 100% specificity for both nurses. All 20 false-negative cases resulted from high scores in the auditory attention screening in CAM-ICU. The ICDSC showed 97% and 94% sensitivity, and 97% and 91% specificity for the two nurses (cutoff >=4). CONCLUSION: In a Japanese cardio-surgical ICU, the ICDSC had a higher sensitivity than the CAM-ICU. PMID- 26685070 TI - Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes. AB - OBJECTIVE: To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. METHODS: In this nationwide program, 669,797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. RESULTS: After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid alpha-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 +/- 1.3 months, the same age as normal children. CONCLUSIONS: ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes. PMID- 26685071 TI - Pediatric Inpatient Readmissions in an Accountable Care Organization. AB - OBJECTIVE: To assess the association between the length of consistent primary care as part of an accountable care organization (attribution length) and population-level and same-hospital readmissions. Readmission studies are generally focused on same-hospital readmissions rather than readmissions to any hospital (population-level readmissions). STUDY DESIGN: A retrospective study of Medicaid claims data for 28,794 unique pediatric patients attributed to a single children's hospital between September 2013 and May 2015. Study used logistic regression to estimate the impact of attribution length on readmissions and a zero-inflated Poisson model to assess the impact of attribution length on readmission cost and readmission days. RESULTS: The study showed attribution length was associated with a significant reduction in the population-level 30-day readmission rate from 8.9%-6.2% (P = .010) primarily by reducing readmissions that occurred at hospitals other than the discharging hospital. There was no significant reduction in the same-hospital readmission rate. Readmissions to a different hospital occurred in 37% of readmissions. Although not significant at the P = .05 level, attribution length was associated with a 44% reduction (P = .100) in 30-day readmission costs or a 5.0% reduction in the cost of an inpatient episode of care and a 53% reduction (P = .019) in readmission days. CONCLUSIONS: Consistent primary care (attribution length) may be able to reduce 30-day, pediatric Medicaid patients' readmissions at the population level. The decrease occurred primarily in readmissions to hospitals other than the discharging hospital. There was no decrease in the rate of same-hospital readmissions. PMID- 26685072 TI - Long-Term Outcome of Catheter-Related Arterial Thrombosis in Infants with Congenital Heart Disease. AB - OBJECTIVES: To investigate the long-term outcome of catheter-related arterial thrombosis in children. STUDY DESIGN: Data from clinical and radiologic long-term follow-up of infants with congenital heart disease developing arterial thrombosis following femoral catheterization are presented. RESULTS: Ninety-five infants with radiologically proven arterial thrombosis because of cardiac catheter (n = 52; 55%) or indwelling arterial catheter (n = 43; 45%) were followed for a median time of 23.5 months (IQR 13.3-47.3). Overall, radiologic complete thrombus resolution was observed in 64 (67%), partial resolution in 8 (9%), and no resolution in 23 (24%) infants. Complete resolution was significantly more frequent in infants with indwelling arterial catheter-related thrombosis compared with cardiac catheter-related thrombosis (P = .001). Patients with complete resolution had a significantly lower blood pressure difference and increased ankle-ankle index compared with patients with partial or no resolution (P < .0001). However, symptoms of claudication were present only in 1 case and clinical significant legs growth retardation (>= 15 mm) was present in 1%. CONCLUSIONS: A significant percentage of persistent occlusion is present in children with arterial catheter-related thrombosis on long-term follow-up. In these children, the magnitude of leg growth retardation is small and possibly not clinically relevant. However, in children with congenital heart disease, the high prevalence of persistent arterial occlusion may hamper future diagnostic and/or interventional catheterization. PMID- 26685068 TI - The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome. AB - X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution. PMID- 26685074 TI - Prevention of Contrast-Induced Nephropathy by Central Venous Pressure-Guided Fluid Administration in Chronic Kidney Disease and Congestive Heart Failure Patients. AB - OBJECTIVES: This study aimed to explore the hemodynamic index-guided hydration method for patients with congestive heart failure (CHF) and chronic kidney disease (CKD) to reduce the risk of contrast-induced nephropathy (CIN) and at the same time to avoid the acute heart failure. BACKGROUND: Patients at moderate or high risk for CIN should receive sufficient hydration before contrast application. METHODS: This prospective, randomized, double-blind, comparative clinical trial enrolled 264 consecutive patients with CKD and CHF undergoing coronary procedures. These patients were randomly assigned to either central venous pressure (CVP)-guided hydration group (n = 132) or the standard hydration group (n = 132). In the CVP-guided group, the hydration infusion rate was dynamically adjusted according to CVP level every hour. CIN was defined as an absolute increase in serum creatinine (SCr) >0.5 mg/dl (44.2 MUmol/l) or a relative increase >25% compared with baseline SCr. RESULTS: Baseline characteristics were well-matched between the 2 groups. The total mean volume of isotonic saline administered in the CVP-guided hydration group was significantly higher than the control group (1,827 +/- 497 ml vs. 1,202 +/- 247 ml; p < 0.001). CIN occurred less frequently in CVP-guided hydration group than the control group (15.9% vs. 29.5%; p = 0.006). The incidences of acute heart failure during the hydration did not differ between the 2 groups (3.8% vs. 3.0%; p = 0.500). CONCLUSIONS: CVP-guided fluid administration can safely and effectively reduce the risk of CIN in patients with CKD and CHF. (Central Venous Pressure Guided Hydration Prevention for Contrast-Induced Nephropathy; NCT02405377). PMID- 26685075 TI - In-Stent Dissection Causes No Flow During Percutaneous Coronary Intervention. PMID- 26685073 TI - Assessment of Quality of Life in Young Patients with Single Ventricle after the Fontan Operation. AB - OBJECTIVES: To assess self-reported quality of life (QOL) in a large multicenter cohort of adolescent and young adults surviving Fontan. STUDY DESIGN: Cross sectional. The Pediatric Quality of Life Inventory (PedsQL) was administered to 408 survivors of Fontan ages 13-25 years enrolled in the Pediatric Heart Network Fontan Follow-up Study. Subjects also completed either the Child Health Questionnaire (age <19 years) or Short Form Health Survey (age >= 19 years). PedsQL data were compared with matched controls without a chronic health condition. Correlations between the measures were examined. RESULTS: Mean PedsQL scores for subjects receiving Fontan were significantly lower than those for the control group for physical and psychosocial QOL (P < .001). Overall, 45% of subjects receiving Fontan had scores in the clinically significant impaired range for physical QOL with 30% in the impaired range for psychosocial QOL. For each 1 year increase in age, the physical functioning score decreased by an average of 0.76 points (P = .004) and the emotional functioning score decreased by an average of 0.64 points (P = .03). Among subjects >=19 years of age, the physical functioning score decreased by an average of 2 points for each year increase in age (P = .02). PedsQL scale scores were significantly correlated with conceptually related Child Health Questionnaire (P < .001) and Short Form Health Survey scores (P < .001). CONCLUSIONS: Survivors of Fontan are at risk for significantly impaired QOL which may decline with advancing age. Routine assessment of QOL is essential to inform interventions to improve health outcomes. The PedsQL allowed QOL assessment from pediatrics to young adulthood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00132782. PMID- 26685076 TI - Improving Intravenous Fluid Therapy for Prevention of Contrast-Induced Nephropathy: How to Give More Without Causing Heart Failure. PMID- 26685077 TI - Collapse of a Bioresorbable Novolimus-Eluting Coronary Scaffold. PMID- 26685078 TI - First Successful Transfemoral Implantation of an Edwards Sapien XT Valve in a Direct Flow Valve After Early Restenosis. PMID- 26685079 TI - Hemodynamic and Intravascular Ultrasound Evaluation of an Infrarenal Aortic Stenosis. PMID- 26685080 TI - Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel. AB - Aquaporins (AQPs) are a family of membrane proteins that function as channels facilitating water transport in response to osmotic gradients. These play critical roles in several normal physiological and pathological states and are targets for drug discovery. Selective inhibition of the AQP1 water channel may provide a new approach for the treatment of several disorders including ocular hypertension/glaucoma, congestive heart failure, brain swelling associated with a stroke, corneal and macular edema, pulmonary edema, and otic disorders such as hearing loss and vertigo. We developed a high-throughput assay to screen a library of compounds as potential AQP1 modulators by monitoring the fluorescence dequenching of entrapped calcein in a confluent layer of AQP1-overexpressing CHO cells that were exposed to a hypotonic shock. Promising candidates were tested in a Xenopus oocyte-swelling assay, which confirmed the identification of two lead classes of compounds belonging to aromatic sulfonamides and dihydrobenzofurans with IC50 s in the low micromolar range. These selected compounds directly inhibited water transport in AQP1-enriched stripped erythrocyte ghosts and in proteoliposomes reconstituted with purified AQP1. Validation of these lead compounds, by the three independent assays, establishes a set of attractive AQP1 blockers for developing novel, small-molecule functional modulators of human AQP1. PMID- 26685082 TI - Using Nurse Ratings of Physician Communication in the ICU To Identify Potential Targets for Interventions To Improve End-of-Life Care. AB - BACKGROUND: Communication among doctors, nurses, and families contributes to high quality end-of-life care, but is difficult to improve. OBJECTIVE: Our objective was to identify aspects of communication appropriate for interventions to improve quality of dying in the intensive care unit (ICU). METHODS: This observational study used data from a cluster-randomized trial of an interdisciplinary intervention to improve end-of-life care at 15 Seattle/Tacoma area hospitals (2003-2008). Nurses completed surveys for patients dying in the ICU. We examined associations between nurse-assessed predictors (physician-nurse communication, physician-family communication) and nurse ratings of patients' quality of dying (nurse-QODD-1). RESULTS: Based on 1173 nurse surveys, four of six physician-nurse communication topics were positively associated with nurse-QODD-1: family questions, family dynamics, spiritual/religious issues, and cultural issues. Discussions between nurses and physicians about nurses' concerns for patients or families were negatively associated. All physician-family communication ratings, as assessed by nurses, were positively associated with nurse-QODD-1: answering family's questions, listening to family, asking about treatments patient would want, helping family decide patient's treatment wishes, and overall communication. Path analysis suggested overall physician-family communication and helping family incorporate patient's wishes were directly associated with nurse QODD-1. CONCLUSIONS: Several topics of physician-nurse communication, as rated by nurses, were associated with higher nurse-rated quality of dying, whereas one topic, nurses' concerns for patient or family, was associated with poorer ratings. Higher nurse ratings of physician-family communication were uniformly associated with higher quality of dying, highlighting the importance of this communication. Physician support of family decision making was particularly important, suggesting a potential target for interventions to improve end-of-life care. PMID- 26685083 TI - Apoplectic Leiomyomas: A Morphologic Analysis of 100 Cases Highlighting Unusual Features. AB - Leiomyomas with apoplectic change related to progestational effect have not received much attention in the literature and in our experience frequently cause diagnostic difficulty. We reviewed 100 apoplectic leiomyomas to characterize their broad histologic spectrum. The tumors occurred over a wide age range (mean, 41 y), and although 2 patients were pregnant, in the vast majority the apoplectic changes were likely due to progestins administered to help control symptoms related to the leiomyomas. Leiomyomas were multiple in 77% of patients, averaged 6 cm, and frequently showed gross features of hemorrhage, necrosis, cyst formation, softening, or color different than the usual banal leiomyoma. Microscopic examination typically revealed multiple stellate to ovoid zones with a hypercellular periphery and central hemorrhage, necrosis, or hyalinization. The hypercellular areas were often dominated by cells with eosinophilic cytoplasm, pyknotic nuclei, and increased mitoses (up to 14/10 high-power fields), but most tumors showed no appreciable cytologic atypia in these regions. Edema was noted in 95%, a hyalinized and/or myxoid matrix in 92%, and cyst formation in 42%. Because of these unusual features, difficulty often arose in determining whether the tumors were benign, malignant, or of uncertain malignant potential. Recognition of their wide morphologic spectrum will enable classification in the benign category and avoid undue patient anxiety and potentially unnecessary aggressive management. PMID- 26685084 TI - CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas. AB - The CIC gene rearrangement exists in a subset of small round cell sarcomas. As the nosologic relationship of these sarcomas to Ewing sarcomas remains undetermined, we examined 20 CIC-rearranged sarcomas to compare their clinicopathologic features with those of Ewing sarcomas. The CIC-rearranged sarcomas were from a group of 14 men and 6 women with a median age of 24.5 years. The primary tumor sites included the limbs, trunk wall, internal trunk, lung, cerebrum, and pharynx. A comparison of the demographic and clinical characteristics of the 20 patients with CIC-rearranged sarcomas with those of the 53 near-consecutive patients with EWSR1-rarranged Ewing sarcomas showed that there were no differences with respect to their ages and sexes. Although none of the CIC-rearranged sarcomas arose in the bone, 40% of the Ewing sarcomas primarily affected the skeleton. The overall survival of patients with Ewing sarcomas was significantly better than that for patients with CIC-rearranged sarcomas. A histologic comparison of the CIC-rearranged sarcomas with 20 EWSR1 rearranged Ewing sarcomas showed significantly higher degrees of lobulation, nuclear pleomorphism, the prominence of the nucleoli, spindle cell elements, and myxoid changes in the CIC-rearranged sarcomas. Distinguishing immunohistochemical features included heterogenous CD99 reactivity, nuclear WT1 expression, and calretinin expression in the CIC-rearranged sarcomas and NKX2.2 expression in the Ewing sarcomas. CIC-rearranged sarcomas are distinct from Ewing sarcomas clinically, morphologically, and immunohistochemically, and they should be considered a separate entity rather than being grouped within the same family of tumors. PMID- 26685085 TI - An International Ki67 Reproducibility Study in Adrenal Cortical Carcinoma. AB - Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis. The interobserver variation was statistically significant (P<0.001) in the absence of any correlation between the various methods. Subsequently, 61 static images were distributed among 15 observers who were instructed to follow a category-based scoring approach. Low levels of interobserver (F=6.99; Fcrit=1.70; P<0.001) as well as intraobserver concordance (n=11; Cohen kappa ranging from -0.057 to 0.361) were detected. To improve harmonization of Ki67 analysis, we tested the utility of an open-source Galaxy virtual machine application, namely Automated Selection of Hotspots, in 61 virtual slides. The software-provided Ki67 values were validated by digital image analysis in identical images, displaying a strong correlation of 0.96 (P<0.0001) and dividing the cases into 3 classes (cutoffs of 0%-15%-30% and/or 0%-10%-20%) with significantly different overall survivals (P<0.05). We conclude that current practices in Ki67 scoring assessment vary greatly, and interobserver variation sets particular limitations to its clinical utility, especially around clinically relevant cutoff values. Novel digital microscopy-enabled methods could provide critical aid in reducing variation, increasing reproducibility, and improving reliability in the clinical setting. PMID- 26685086 TI - Hepatocellular Neoplasms Arising in Association With Androgen Use. AB - Correlation between androgen use and hepatocellular neoplasia is well established. However, there are no detailed studies of the histopathology and immunohistochemical/molecular profile of these tumors. We studied 9 patients with androgen-associated hepatocellular neoplasms. In addition to histology, immunostains for liver fatty acid-binding protein, beta-catenin, glutamine synthetase, C-reactive protein, and serum amyloid A were utilized for tumor subtyping. Molecular testing using Solid Tumor Targeted Cancer Panel was performed on 3 cases. The neoplasms were predominantly seen in male individuals (7/9). Two patients (22%) had multifocal lesions. All lesions had architectural and 4/9 had cytologic atypia. Cholestasis was present in 6/9 cases. Reticulin was focally disrupted in 5/9 cases. Given the clinical setting, all lesions were classified as well-differentiated hepatocellular neoplasms of uncertain malignant potential. In cases with follow-up (6/9 cases, 67%), there were no recurrences or metastases. On the basis of the immunoprofile, 7 (78%) cases were beta-catenin activated (including 1 hepatic adenoma with concurrent hepatocyte nuclear factor 1alpha inactivation) and 2 (22%) had inflammatory phenotype. Somatic mutations in CTNNB1 were detected in all 3 tested cases (all beta-catenin activated by immunostain), all involving exon-3. Our data indicate that androgen-associated hepatocellular neoplasms most often develop in male individuals and always show some degree of atypia and/or focal reticulin disruption. Most are beta-catenin activated, often harboring CTNNB1 exon-3 mutations, and a minority is inflammatory type. Although beta-catenin and inflammatory pathways likely play a role in pathogenesis, the heterogenous molecular profile suggests there are other (yet to be characterized) primary oncogenic mechanisms in this unique tumor type. PMID- 26685088 TI - The effect of anodal transcranial direct current stimulation on motor sequence learning in healthy individuals: A systematic review and meta-analysis. AB - A large number of studies have indicated the effect of anodal transcranial direct current stimulation (a-tDCS) on the primary motor cortex (M1) during motor skill training. The effects of a-tDCS on different stages of motor sequence learning are not yet completely understood. The purpose of this meta-analysis was to determine the effects of single and multiple sessions of a-tDCS on two different tasks: the sequential finger tapping task/serial reaction time task (SEQTAP/SRTT) and the sequential visual isometric pinch task (SVIPT). We searched electronic databases for M1 a-tDCS studies. Thirteen studies met the inclusion criteria. The results indicate that application of multiple sessions of a-tDCS, compared to single session a-tDCS induced a significant improvement in skill in both SEQTAP/SRTT and SVIPT. Retention after a single day and multiple days of a-tDCS was statistically significant for the SEQTAP/SRTT task but not for SVIPT. Therefore, our findings suggest that application of M1 a-tDCS across the three or five consecutive days can be helpful to improve motor sequence learning. PMID- 26685087 TI - A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas. AB - Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (<50% of tumor cells positive), or diffuse (>=50% tumor cells positive) except for p53 (classified as "wild-type" or "mutation-type"), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas), and MMR proteins (categorized as retained or lost). There was positive staining with CK7 (47/47-45 diffuse, 2 focal), MUC6 (17/21-6 diffuse, 11 focal), carcinoembryonic antigen (25/31-12 diffuse, 13 focal), carbonic anhydrase IX (20/24-8 diffuse, 12 focal), PAX8 (32/47-20 diffuse, 12 focal), CA125 (36/45-5 diffuse, 31 focal), CA19.9 (11/11-8 diffuse, 3 focal), hepatocyte nuclear factor 1 beta (13/14-12 diffuse, 1 focal), CDX2 (24/47-4 diffuse, 20 focal), CK20 (23/47-6 diffuse, 17 focal), and p16 (18/47-4 diffuse, 14 focal). Most cases were negative with estrogen receptor (29/31), progesterone receptor (10/11), PAX2 (18/19), and HER2 (25/26). p53 showed "wild-type" and "mutation-type" staining in 27 of 46 and 19 of 46 cases, respectively. MMR protein expression was retained in 19 of 20 cases with loss of MSH6 staining in 1 patient with Lynch syndrome. Molecular studies for HPV were undertaken in 2 tumors, which exhibited diffuse "block-type" immunoreactivity with p16, and both were negative. This is the first detailed immunohistochemical study of a large series of gastric-type adenocarcinomas of the lower female genital tract. Our results indicate immunophenotypic overlap with pancreaticobiliary adenocarcinomas but suggest that PAX8 immunoreactivity may be especially useful in distinguishing gastric-type adenocarcinomas from pancreaticobiliary and other nongynecologic adenocarcinomas, which are usually negative. Diffuse "block-type" p16 immunoreactivity in a cervical adenocarcinoma is not necessarily indicative of a high-risk HPV-associated tumor. PMID- 26685089 TI - Let the man choose what to do: Neural correlates of spontaneous lying and truth telling. AB - Many previous functional magnetic resonance imaging (fMRI) studies on deception used a paradigm of "instructed lies", which is different than other, more spontaneous forms of lying behavior. The present study aimed to investigate the neural processes underlying spontaneous and instructed lying and truth-telling, and to investigate the different mechanisms involved. This study used a modified sic bo gambling game with real payoffs in order to induce lying. In the spontaneous sessions, the participants themselves decided whether or not to lie, whereas in the instructed sessions they were explicitly told to respond either honestly or dishonestly. In the spontaneous lying (vs. truth-telling) condition, the subgenual anterior cingulate cortex (sACC) showed significantly higher activity, whereas the right dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and inferior parietal lobule (IPL) were more strongly activated when participants spontaneously told the truth (vs. lied). Our results suggest that the extra cognitive control required for suppressing the self interest motives in spontaneous truth-telling is associated with higher activity in the fronto-parietal network, while the process of negative emotion in spontaneous lying induced greater involvement of the sACC. Although similar to spontaneous deception, instructed deception engenders greater involvement of the right inferior frontal gyrus (IFG), left supplementary motor area (SMA), anterior cingulate cortex (ACC), IPL and superior frontal gyrus (SFG) compared to baseline, instructed decisions did not elicit similar activation patterns in the regions of sACC, DLPFC, VLPFC and IPL which were sensitive to either spontaneous truth-telling or lying. PMID- 26685090 TI - Nurses' involvement in end-of-life care of patients after a do not resuscitate decision on general medical units in Saudi Arabia. AB - OBJECTIVES: To describe the essence of the nurses' lived experience and explore the meaning of their involvement in end-of-life care after a do-not-resuscitate decision has been made. RESEARCH METHODOLOGY/DESIGN: The research design embraced qualitative, exploratory and descriptive approaches utilising aspects of phenomenology. Purposive sampling of twenty-six registered nurses was used. Data was collected using the reflective journaling technique and were analysed using an integrated approach. Field notes were also used as a mean to enrich the description of the findings contextually. SETTING: Medical units in Saudi Arabia. RESULTS: Three main themes emerged: exhausted medical treatment, continuity of nursing care and cultural considerations in nursing care. Related sub-themes were also identified as an extension to the description of the main themes. CONCLUSION: The findings affirm that nurses working on medical units continue to maintain a constant level of care for patients and families after the do-not resuscitate decision. Nurses found that caring for dying patients was a rewarding and worthwhile experience, albeit a challenging and demanding one. The findings suggest that improvement in end-of-life care would be best achieved by collaborative and interdisciplinary practices amongst the health care team members. PMID- 26685091 TI - Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014. AB - BACKGROUND: We aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014. METHODS: We used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction. RESULTS: 1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Maori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group. CONCLUSION: This study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza. PMID- 26685092 TI - Hepatitis B vaccination uptake and correlates of serologic response among HIV infected and uninfected men who have sex with men (MSM) in Bangkok, Thailand. AB - BACKGROUND: Vaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM. METHODOLOGY: HBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses. RESULTS: 511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p<0.0001). Median pre-vaccination IgG was higher among non responders than responders overall (1238.9.0 vs. 1057.0mg/dL, p=0.003) and among HIV-infected participants (1534.0 vs. 1244.5mg/dL, p=0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3mg/dL, p=0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1mg/dL, respectively, p<0.0001). Among HIV-infected participants, median CD4 count in non responders was 378 cells/MUL vs. 431 cells/MUL in responders (p=0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p=0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p<0.01). CONCLUSIONS: HIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure. PMID- 26685093 TI - Immunogenicity of adenovirus-derived porcine parvovirus-like particles displaying B and T cell epitopes of foot-and-mouth disease. AB - Virus-like particles (VLPs) vaccines combine many of the advantages of whole virus vaccines and recombinant subunit vaccines, integrating key features that underlay their immunogenicity, safety and protective potential. We have hypothesized here the effective insertion of the VP1 epitopes (three amino acid residues 21-40, 141-160 and 200-213 in VP1, designated VPe) of foot-and-mouth disease (FMDV) within the external loops of PPV VP2 could be carried out without altering assembly based on structural and antigenic data. To investigate the possibility, development of two recombinant adenovirus rAd-PPV:VP2-FMDV:VPe a or rAd-PPV:VP2-FMDV:VPe b were expressed in HEK-293 cells. Out of the two insertion strategies tested, one of them tolerated an insert of 57 amino acids in one of the four external loops without disrupting the VLPs assembly. Mice were inoculated with the two recombinant adenoviruses, and an immunogenicity study showed that the highest levels of FMDV-specific humoral responses and T cell proliferation could be induced by rAd-PPV:VP2-FMDV:VPe b expressing hybrid PPV:VLPs (FMDV) in the absence of an adjuvant. Then, the protective efficacy of inoculating swine with rAd-PPV:VP2-FMDV:VPe b was tested. All pigs inoculated with rAd-PPV:VP2-FMDV:VPe b were protected from viral challenge, meanwhile the neutralizing antibody titers were significantly higher than those in the group inoculated with swine FMD type O synthetic peptide vaccine. Our results clearly demonstrate the potential usefulness of adenovirus-derived PPV VLPs as a vaccine strategy in prevention of FMDV. PMID- 26685094 TI - Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6. AB - The matrine-type alkaloid, oxymatrine inhibits hepatitis B virus (HBV) replication but very little is known about these effects in other matrine-type alkaloids, including sophoridine and sophocarpine. Therefore, we compared the in vitro anti-HBV effects of matrine, oxymatrine, sophocarpine, and sophoridine by treating an HBV-transfected cell line (HepG2.2.15) with 0.4-1.6mM of the compounds for 24 or 72h. The levels of the HBV surface antigen (HBsAg) and e antigen (HBeAg) in the culture medium, as well as the intracellular and extracellular HBV DNA levels, were determined. Metabolomic analysis and detection of the mRNA level of p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor-associated factor (TRAF) 6, extracellular signal-regulated kinase (ERK) 1, NOD-like receptor family pyrin domain containing 10 (NLRP10), and caspase-1 were conducted in sophoridine-treated HepG2.2.15 cells. HepG2.2.15 cell exposure to 0.4-1.6mM sophocarpine or sophoridine for 24h reduced the HBsAg level of the medium more effectively than exposure to matrine and oxymatrine did, and reduced the HBeAg levels more effectively than these compounds did at 1.6mM. Sophoridine (0.4-1.6mM) reduced the cell medium HBV DNA levels more than the same concentrations of matrine, oxymatrine, or sophocarpine did. After 72h, 0.4 and 0.8mM sophoridine reduced HBsAg and intracellular HBV DNA levels more potently than matrine, oxymatrine, or sophocarpine did. Furthermore, sophoridine (0.8mM) potently reduced the cell medium HBeAg levels while the metabolomic analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine for 72h exhibited reduced cycloleucine and phytosphingosine levels. In addition, the mRNA expression analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine showed reduced levels of p38 MAPK, TRAF6, ERK1, NLRP10, and caspase-1. Sophoridine produced more potent anti-HBV effects than matrine, oxymatrine, and sophocarpine did. These effects may be related to the sophoridine-mediated reduction of p38 MAPK and TRAF6 levels. PMID- 26685095 TI - A model for promoting physical activity among rural South African adolescent girls. AB - BACKGROUND: In South Africa, the expanding epidemic of non-communicable diseases is partly fuelled by high levels of physical inactivity and sedentary behaviour. Women especially are at high risk, and interventions promoting physical activity are urgently needed for girls in their adolescence, as this is the time when many girls adopt unhealthy lifestyles. OBJECTIVE: This qualitative study aimed to identify and describe facilitating factors and barriers that are associated with physical activity among adolescent girls in rural, north-eastern South Africa and, based on these, to develop a model for promoting leisure-time physical activity within this population. DESIGN: The study was conducted in and around three secondary schools. Six focus group discussions were conducted with adolescent girls from the schools, and seven qualitative interviews were held with sports teachers and youth leaders. The data were subjected to thematic analysis. RESULTS: Seven thematic areas were identified, each of which was associated with the girls' self-reported levels of physical activity. The thematic areas are 1) poverty, 2) body image ideals, 3) gender, 4) parents and home life, 5) demographic factors, 6) perceived health effects of physical activity, and 7) human and infrastructural resources. More barriers to physical activity were reported than facilitating factors. CONCLUSIONS: Analysis of the barriers found in the different themes indicated potential remedial actions that could be taken, and these were synthesised into a model for promoting physical activity among South African adolescent girls in resource-poor environments. The model presents a series of action points, seen both from the 'supply-side' perspective (such as the provision of resources and training for the individuals, schools, and organisations which facilitate the activities) and from the 'demand side' perspective (such as the development of empowering messages about body image for teenage girls, and encouraging more parental involvement). The development of physical activity interventions that incorporate this supply- and demand-side model would represent an additional tool for ongoing efforts aimed at tackling the expanding non-communicable disease epidemic in South Africa, and in other resource-constrained settings undergoing rapid health transitions. PMID- 26685096 TI - Effect of rainbow trout (Oncorhynchus mykiss) seminal plasma on the post-thaw quality of ram semen cryopreserved in a soybean lecithin-based or egg yolk-based extender. AB - The aim of the current study was to evaluate the effects of different concentrations of rainbow trout seminal plasma (RTSP) (0.1%, 1% and 10%) in extenders containing either egg yolk or lecithin for use in Awassi ram semen cryopreservation. Pooled sperm were diluted in a two-step dilution method to a final concentration of 1/5 (semen/extender) in egg yolk or lecithin extender containing no RTSP, 0.1%, 1% or 10% RTSP (v/v). Semen samples were assessed for sperm motility, plasma membrane integrity [hypoosmotic swelling test (HOST) and Hoechst 33258] and defective acrosomes [FITC-conjugated Pisum sativum agglutinin (PSA-FITC)] at the following five time points: after dilution with extender A; after equilibration; and post-thaw at 0h, 3h and 5h. Malondialdehyde (MDA) was examined only after thawing. Freezing and thawing procedures (dilution, equilibration and post-thaw incubation at 0h, 3h and 5h) negatively affected the motility (P<0.001) and acrosome integrity (P<0.001). Additionally, freezing and thawing negatively affected the plasma membrane integrity, as determined by the HOST and Hoechst 33258 (P<0.001). The extender group affected the motility (P<0.001) and the HOST results (P<0.001). Levels of MDA in the egg yolk extender with 1% RTSP group were significantly lower than in the lecithin control group (P<0.05). In conclusion, the egg yolk extender groups that were supplemented with 10% and 1% RTSP provided greater cryoprotective effects for semen survivability during 5h incubation than the other extender groups. PMID- 26685097 TI - Rituximab-ABV(D) for patients with Nodular lymphocyte predominant Hodgkin lymphoma ineligible for radiation therapy. PMID- 26685098 TI - Cyclooxygenase 2: its regulation, role and impact in airway inflammation. AB - Cyclooxygenase 2 (COX-2: official gene symbol - PTGS2) has long been regarded as playing a pivotal role in the pathogenesis of airway inflammation in respiratory diseases including asthma. COX-2 can be rapidly and robustly expressed in response to a diverse range of pro-inflammatory cytokines and mediators. Thus, increased levels of COX-2 protein and prostanoid metabolites serve as key contributors to pathobiology in respiratory diseases typified by dysregulated inflammation. But COX-2 products may not be all bad: prostanoids can exert anti inflammatory/bronchoprotective functions in airways in addition to their pro inflammatory actions. Herein, we outline COX-2 regulation and review the diverse stimuli known to induce COX-2 in the context of airway inflammation. We discuss some of the positive and negative effects that COX-2/prostanoids can exert in in vitro and in vivo models of airway inflammation, and suggest that inhibiting COX 2 expression to repress airway inflammation may be too blunt an approach; because although it might reduce the unwanted effects of COX-2 activation, it may also negate the positive effects. Evidence suggests that prostanoids produced via COX 2 upregulation show diverse actions (and herein we focus on prostaglandin E2 as a key example); these can be either beneficial or deleterious and their impact on respiratory disease can be dictated by local concentration and specific interaction with individual receptors. We propose that understanding the regulation of COX-2 expression and associated receptor-mediated functional outcomes may reveal number of critical steps amenable to pharmacological intervention. These may prove invaluable in our quest towards future development of novel anti-inflammatory pharmacotherapeutic strategies for the treatment of airway diseases. PMID- 26685099 TI - Combined non-pharmacological interventions for newborn pain relief in two degrees of pain procedures: A randomized clinical trial. AB - BACKGROUND: Non-pharmacological interventions are effective neonatal pain reduction strategies. We aimed to study the effects of non-nutritive sucking (NNS) and swaddling on infants' behavioural and physiological parameters during shallow or deep heel stick procedures. METHOD: In this prospective, multi centred, randomized controlled clinical trial, we enrolled 671 newborns. The infants undergoing shallow or deep heel stick procedures were randomized into four groups: oral sucrose (routine care, group S), oral sucrose combined with NNS (group NS), oral sucrose combined with swaddling (group SS) and oral sucrose combined with NNS and swaddling (group NSS). The behavioural responses were evaluated by the Revised Neonatal Facial Coding System and the physiological signals were monitored by electrocardiogram monitors. RESULTS: A significant synergistic analgesic effect was observed between the NS and SS groups in both the shallow (F = 5.952, p = 0.015) and deep heel stick (F = 7.452, p = 0.007) procedure. NSS group exhibited the lowest pain score. For the deep heel stick procedure, the NS group had a significantly lower increase in heart rate (HR)% and decrease in SPO2 % than the S group (F = 17.540, p = 0.000, F = 10.472, p = 0.001), while this difference was not observed in the shallow heel stick procedure. No difference was found between the S and SS groups, in terms of different physiological parameters. CONCLUSION: Non-nutritive sucking and swaddling had synergistic effects on pain relief when used with oral sucrose. For the deep heel stick procedure, oral sucrose combined with NNS and swaddling provided the best pain relief effect. For the shallow heel stick procedure, addition of NNS and swaddling did not improve the effects. PMID- 26685100 TI - Dysbindin-1 modifies signaling and cellular localization of recombinant, human D3 and D2 receptors. AB - Dystrobrevin binding protein-1 (dysbindin-1), a candidate gene for schizophrenia, modulates cognition, synaptic plasticity and frontocortical circuitry and interacts with glutamatergic and dopaminergic transmission. Loss of dysbindin-1 modifies cellular trafficking of dopamine (DA) D2 receptors to increase cell surface expression, but its influence upon signaling has never been characterized. Further, the effects of dysbindin-1 upon closely related D3 receptors remain unexplored. Hence, we examined the impact of dysbindin-1 (isoform A) co-expression on the localization and coupling of human D2L and D3 receptors stably expressed in Chinese hamster ovary or SH-SY5Y cells lacking endogenous dysbindin-1. Dysbindin-1 co-transfection decreased cell surface expression of both D3 and D2L receptors. Further, while their affinity for DA was unchanged, dysbindin-1 reduced the magnitude and potency of DA-induced adenylate cylase recruitment/cAMP production. Dysbindin-1 also blunted the amplitude of DA induced phosphorylation of ERK1/2 and Akt at both D2L and D3 receptors without, in contrast to cAMP, affecting the potency of DA. Interference with calveolin/clathrin-mediated processes of internalization prevented the modification by dysbindin-1 of ERK1/2 and adenylyl cyclase stimulation at D2L and D3 receptors. Finally, underpinning the specificity of the influence of dysbindin 1 on D2L and D3 receptors, dysbindin-1 did not modify recruitment of adenylyl cyclase by D1 receptors. These observations demonstrate that dysbindin-1 influences cell surface expression of D3 in addition to D2L receptors, and that it modulates activation of their signaling pathways. Accordingly, both a deficiency and an excess of dysbindin-1 may be disruptive for dopaminergic transmission, supporting its link to schizophrenia and other CNS disorders. Dysbindin-1, a candidate gene for schizophrenia, alters D2 receptors cell surface expression. We demonstrate that dysbindin-1 expression also influences cell surface levels of D3 receptors. Further, Dysbindin-1 reduces DA-induced adenylate cylase recruitment/cAMP production and modifies major signaling pathways (Akt and extracellular signal-regulated kinases1/2 (ERK1/2)) of both D2 and D3 receptors. Dysbindin-1 modulates thus D2 and D3 receptor signaling, supporting a link to schizophrenia. PMID- 26685101 TI - Circular DNA by "Bis-Click" Ligation: Template-Independent Intramolecular Circularization of Oligonucleotides with Terminal Alkynyl Groups Utilizing Bifunctional Azides. AB - A highly effective and convenient "bis-click" strategy was developed for the template-independent circularization of single-stranded oligonucleotides by employing copper(I)-assisted azide-alkyne cycloaddition. Terminal triple bonds were incorporated at both ends of linear oligonucleotides. Alkynylated 7-deaza-2' deoxyadenosine and 2'-deoxyuridine residues with different side chains were used in solid-phase synthesis with phosphoramidite chemistry. The bis-click ligation of linear 9- to 36-mer oligonucleotides with 1,4-bis(azidomethyl)benzene afforded circular DNA in a simple and selective way; azido modification of the oligonucleotide was not necessary. Short ethynyl side chains were compatible with the circularization of longer oligonucleotides, whereas octadiynyl residues were used for short 9-mers. Compared with linear duplexes, circular bis-click constructs exhibit a significantly increased duplex stability over their linear counterparts. The intramolecular bis-click ligation protocol is not limited to DNA, but may also be suitable for the construction of other macrocycles, such as circular RNAs, peptides, or polysaccharides. PMID- 26685102 TI - A novel bioprinting method and system for forming hybrid tissue engineering constructs. AB - Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(epsilon-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (~6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance surrounding the conduit indicated that culture media effectively diffused through the conduit and fed the cells. The results suggest that the developed technology is potent to form functional TECs composed of rigid and soft biomaterials. PMID- 26685103 TI - Robust exchangeability designs for early phase clinical trials with multiple strata. AB - Clinical trials with multiple strata are increasingly used in drug development. They may sometimes be the only option to study a new treatment, for example in small populations and rare diseases. In early phase trials, where data are often sparse, good statistical inference and subsequent decision-making can be challenging. Inferences from simple pooling or stratification are known to be inferior to hierarchical modeling methods, which build on exchangeable strata parameters and allow borrowing information across strata. However, the standard exchangeability (EX) assumption bears the risk of too much shrinkage and excessive borrowing for extreme strata. We propose the exchangeability nonexchangeability (EXNEX) approach as a robust mixture extension of the standard EX approach. It allows each stratum-specific parameter to be exchangeable with other similar strata parameters or nonexchangeable with any of them. While EXNEX computations can be performed easily with standard Bayesian software, model specifications and prior distributions are more demanding and require a good understanding of the context. Two case studies from phases I and II (with three and four strata) show promising results for EXNEX. Data scenarios reveal tempered degrees of borrowing for extreme strata, and frequentist operating characteristics perform well for estimation (bias, mean-squared error) and testing (less type-I error inflation). PMID- 26685104 TI - Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice. AB - Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68-3.72; TLR7 5.57-3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3 induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35-65%; TLR7 37-63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during pregnancy and have a potential therapeutic role in pre-eclampsia treatment. PMID- 26685105 TI - Assessment of Regional Xenon Ventilation, Perfusion, and Ventilation-Perfusion Mismatch Using Dual-Energy Computed Tomography in Chronic Obstructive Pulmonary Disease Patients. AB - OBJECTIVES: The aim of this study was to assess the feasibility of combined xenon enhanced ventilation (V) and iodine-enhanced perfusion (Q) dual-energy computed tomography (DECT) to evaluate regional V and Q status in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Combined V and Q DECT imaging was performed in 52 prospectively enrolled male COPD patients. Virtual noncontrast images, V maps, and Q maps were anatomically coregistered with deformable registration and evaluated using in-house software. After normalization of the V and Q values of each pixel, normalized V and Q, V/Qratio, and VQmin (ie, the smaller of the V and Q in each pixel) maps were generated. For visual analysis, the V/Qratio pattern was determined to be matched, mismatched, or reversed mismatched and compared with the regional disease patterns--emphysema with/without bronchial wall thickening, bronchial wall thickening, or normal parenchyma--in each segment. The mean V, Q, V/Qratio, and VQmin values and the standard deviation of the V/Qratio (V/QSD) of each patient were quantified and compared with pulmonary function test (PFT) parameters using the Pearson correlation test. RESULTS: Segments with normal parenchyma showed a matched V/Qratio pattern, whereas segments with bronchial wall thickening commonly showed a reversed mismatched V/Qratio pattern. In the emphysema areas, the matched, mismatched, and reversed mismatched patterns were mixed without a dominant pattern. In quantitative analysis, the mean V, Q, VQmin, and V/Qratio values were significantly and positively correlated with PFT parameters (r = 0.290-0.819; P < 0.05). The V/QSD was significantly and negatively correlated with PFT parameters (r = -0.439 to -0.736; P < 0.001). VQmin values showed the best correlation with PFT parameters (r = 0.483-0.819; P < 0.001). CONCLUSIONS: Visual and quantitative assessment of the regional V, Q, V/Qratio, and VQmin is feasible with combined V and Q DECT imaging and significantly correlate with PFT results in COPD patients. Assessing disease patterns using conventional computed tomography images may not provide correct evaluation of regional V and Q in COPD patients with emphysema. PMID- 26685106 TI - Six-Fold Acceleration of High-Spatial Resolution 3D SPACE MRI of the Knee Through Incoherent k-Space Undersampling and Iterative Reconstruction-First Experience. AB - PURPOSE: The aim of this study was to prospectively test the hypothesis that 6 fold acceleration of a 3-dimensional (3D) turbo spin echo (TSE) magnetic resonance imaging (MRI) pulse sequence with k-space undersampling and iterative reconstruction is feasible for fast high spatial resolution MRI of the knee, while yielding similar image quality and diagnostic performance when compared with a conventional 2-dimensional (2D) TSE MRI standard. MATERIALS AND METHODS: The study was approved by the institutional review board. A 10-minute isotropic 3D TSE knee protocol consisting of accelerated intermediate-weighted (repetition time, 900 milliseconds; echo time, 29 milliseconds; voxel size, 0.5 * 0.5 * 0.5 mm; acquisition time, 4:45 minutes) and fat-saturated T2-weighted (repetition time, 900 milliseconds; echo time, 92 milliseconds; voxel size, 0.5 * 0.5 * 0.5 mm; acquisition time, 5:10 minutes) SPACE (sampling perfection with application optimized contrast using different flip angle evolutions) sequence prototypes was compared against a 20-minute 2D TSE standard protocol. The accelerated SPACE sequences were equipped with an optional variable-density poisson-disc pattern as an undersampling mask. An undersampling factor of 0.17 was chosen (6-fold acceleration compared with an acquisition with full sampling). An iterative, sensitivity encoding-type reconstruction with L1 norm-based regularization term was used. The study was performed on a 3 T MRI system using a 15-channel transmit/receive knee coil. The study groups included 15 asymptomatic volunteers and 15 patient volunteers. Quantitative and qualitative assessments were performed by 2 observers. Outcome variables included signal and contrast-to-noise ratio, image quality, and diagnostic accuracy. Qualitative and quantitative measurements were statistically analyzed using nonparametric tests. P values of less than 0.01 were considered significant. RESULTS: The signal-to-noise ratios of 2D and 3D MRI were similar with the exception of fluid, which was brighter on 2D MRI. Relevant contrast-to-noise ratios of 2D MRI were higher than 3D MRI; however, observer ratings for satisfaction, image quality, and visibility of anatomic structures were similar for 2D and 3D MRI. There was moderate to excellent interobserver (kappa = 0.54-1.00) and intermethod (kappa = 0.54-1.00) agreement for assessing menisci, cartilage, ligaments, cartilage, and bone. Two dimensional and 3D MRI had similar sensitivity (100%/100%, respectively) and specificity (87%/75%, respectively) for detecting 9 meniscal tears (P = 1.00). CONCLUSIONS: We demonstrate the successful clinical implementation of 3D TSE MRI with incoherent k-space undersampling and iterative reconstruction for 6-fold accelerated high spatial resolution isotropic 3D MRI data acquisition. Our preliminary assessments suggest similar image quality and diagnostic performance of a comprehensive 10-minute 3D TSE MRI prototype protocol and 20-minute TSE MRI standard protocol. PMID- 26685107 TI - Connecting the dots between bacterial biofilms and ice cream. AB - Emerging research is revealing a diverse array of interfacially-active proteins that are involved in varied biological process from foaming horse sweat to bacterial raincoat formation. We describe an interdisciplinary approach to study the molecular and biophysical mechanisms controlling the activity of an unusual bacterial protein called BslA. This protein is needed for biofilm formation and forms a protective layer or raincoat over the bacterial community, but also has a multitude of potential applications in multiphase formulations. Here we document our journey from fundamental research to an examination of the applications for this surface-active protein in ice cream. PMID- 26685108 TI - Infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. AB - Familial cases of West syndrome have been reported only in Japan. In that study no chromosomal analyses were made. It has been suggested that microarray analysis should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We report here the first case of infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. The daughter and mother with infantile spasms, and the autistic son had the duplication. The clinical course of infantile spasms was very similar in the mother and daughter. The spasms were primarily considered to be of unknown aetiology. Chromosomal microarray analysis revealed a 6.2 Mb size 15q11.2q13.1 duplication. The duplication belongs to the 15q11q13 duplication syndrome (OMIM 608636) which when maternally derived is characterised by neuro-behavioural disorders like autism, hypotonia, cognitive deficit, language delay and epilepsy. The proportion of patients with unknown aetiology for infantile spasms will decrease when more careful chromosomal studies are made. Our report expands the phenotype of chromosome 15q duplication syndrome and is the first report of this abnormality in two successive generations of infantile spasms. PMID- 26685109 TI - Comparison of Anastrepha ludens (Diptera: Tephritidae) Bisexual and Genetic Sexing (Tapachula-7) Strains: Effect of Hypoxia, Fly Density, Chilling Period, and Food Type on Fly Quality. AB - The use of genetic sexing strain (GSS) insects in the sterile insect technique (SIT) makes necessary the revision of quality parameters of some stressful steps used during the packing process for aerial release because of possible differences in tolerance between fly strains. Here, we determined the effect of three periods of hypoxia (12, 24, and 36 h at pupal stage), three cage densities (1.0, 1.3, and 1.5 flies/cm2), two different foods (protein/sugar (1/24) and Mubarqui), and three chilling times (20 min [control], 90, and 180 min) on the quality parameters of flies of two Anastrepha ludens (Loew) strains (bisexual and GSS Tapachula-7). In general, the response to stressful conditions of both fly strains was qualitatively equivalent but quantitatively different, as flies of both strains responded equally to the stressful factors; however, flies of Tapachula-7 exhibited lower quality parameters than the control flies. Thus, hypoxia affected the flying ability but not the emergence or longevity of flies. The food type affected the adult weight; protein/sugar produced heavier flies that also survived longer and had a greater mating propensity. Flies under the lowest density were better fliers that those at the other two densities. Increasing chilling time reduced flight ability but not longevity or mating propensity. The implications of these findings for the use of A. ludens GSS in SIT programs are discussed herein. PMID- 26685110 TI - Development and Evaluation of Degree-Day Models for Acrolepiopsis assectella (Lepidoptera: Acrolepiidae) Based on Hosts and Flight Patterns. AB - The leek moth, Acrolepiopsis assectella (Zeller), was first discovered in Ottawa, Canada, during the 1993 growing season, representing the first known occurrence of this species in North America. Since then, it has become a significant concern in Allium vegetable production including garlic, leeks, and onions. Acrolepiopsis assectella was first detected in the contiguous United States during the 2009 growing season in northern New York. In this study, we evaluated the development of the US A. assectella population in the laboratory and commercial onion fields. Our results showed that this population required 443.9 degree-days to complete its life cycle on onions in the laboratory. The development of A. assectella on onion did not significantly differ from populations reared on garlic or leeks. Field studies revealed three distinct flight periods for overwintered, first- and second-generation adult males in northern New York. Life cycle duration in the field ranged from 4 to 8 wk. The degree-day prediction model evaluated in this study provided accurate estimates of the occurrence of the following generation. We conclude that this model can help growers to implement appropriate management strategies for different life stages in a timely manner and lessen damage by this new invasive pest. PMID- 26685111 TI - Cy-preds: An algorithm and a web service for the analysis and prediction of cysteine reactivity. AB - Cysteine (Cys) is a critically important amino acid, serving a variety of functions within proteins including structural roles, catalysis, and regulation of function through post-translational modifications. Predicting which Cys residues are likely to be reactive is a very sought after feature. Few methods are currently available for the task, either based on evaluation of physicochemical features (e.g., pKa and exposure) or based on similarity with known instances. In this study, we developed an algorithm (named HAL-Cy) which blends previous work with novel implementations to identify reactive Cys from nonreactive. HAL-Cy present two major components: (i) an energy based part, rooted on the evaluation of H-bond network contributions and (ii) a knowledge based part, composed of different profiling approaches (including a newly developed weighting matrix for sequence profiling). In our evaluations, HAL-Cy provided significantly improved performances, as tested in comparisons with existing approaches. We implemented our algorithm in a web service (Cy-preds), the ultimate product of our work; we provided it with a variety of additional features, tools, and options: Cy-preds is capable of performing fully automated calculations for a thorough analysis of Cys reactivity in proteins, ranging from reactivity predictions (e.g., with HAL-Cy) to functional characterization. We believe it represents an original, effective, and very useful addition to the current array of tools available to scientists involved in redox biology, Cys biochemistry, and structural bioinformatics. PMID- 26685112 TI - The Nedd4-1 WW Domain Recognizes the PY Motif Peptide through Coupled Folding and Binding Equilibria. AB - The four WW domains of human Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) interact with the PPxY (PY) motifs of the human epithelial Na(+) channel (hENaC) subunits, with the third WW domain (WW3*) showing the highest affinity. We have shown previously that the alpha-hENaC PY motif binding interface of WW3* undergoes conformational exchange on the millisecond time scale, indicating that conformational sampling plays a role in peptide recognition. To further understand this role, the structure and dynamics of hNedd4-1 WW3* were investigated. The nuclear Overhauser effect-derived structure of apo-WW3* resembles the domain in complex with the alpha-hENaC peptide, although particular side chain conformations change upon peptide binding, which was further investigated by molecular dynamics simulations. Model free analysis of the (15)N nuclear magnetic resonance spin relaxation data showed that the apo and peptide-bound states of WW3* have similar backbone picosecond to nanosecond time scale dynamics. However, apo-WW3* exhibits pronounced chemical exchange on the millisecond time scale that is quenched upon peptide binding. (1)HN and (15)N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments at various temperatures revealed that apo-WW3* exists in an equilibrium between the natively folded peptide binding-competent state and a random coil-like denatured state. The thermodynamics of the folding equilibrium was determined by fitting a thermal denaturation profile monitored by circular dichroism spectroscopy in combination with the CPMG data, leading to the conclusion that the unfolded state is populated to ~ 20% at 37 degrees C. These results show that the binding of the hNedd4-1 WW3* domain to alpha-hENaC is coupled to the folding equilibrium. PMID- 26685113 TI - Is biological mesh interposition a valid option for complex or recurrent rectovaginal fistula? AB - AIM: Many surgical techniques are available for the treatment of rectovaginal fistula (RVF). There is hitherto little information on its treatment by biological mesh interposition. The aim of the present study was to analyse our results of RVF treatment using biological mesh interposition. METHOD: Patients with RVF undergoing biological mesh interposition were identified. Success was defined by the absence of a diverting stoma and/or any vaginal discharge of faeces, flatus or mucous discharge. RESULTS: Ten women [median age 39 (24.5-65) years] were included. Nine (90%) had recurrent RVF, and the median number of previous attempts at closure was 2.5 (0-8). The main cause of RVF was Crohn's disease (40%). All patients had faecal diversion. No intra-operative complications occurred from mesh interposition. Seven (70%) patients developed postoperative morbidity which was major (Dindo III) in two (20%). The primary success rate was 20% (2/10) but final success rate was achieved in 70% after reoperation with other procedures at 11.1 (2.7-13.1) months of follow-up. CONCLUSION: The study has shown disappointing results with biological mesh interposition for RVF with a healing rate lower than achieved by gracilis muscle interposition. PMID- 26685114 TI - Direct Conversion of Cellulose into Ethyl Lactate in Supercritical Ethanol-Water Solutions. AB - Biomass-derived ethyl lactate is a green solvent with a growing market as the replacement for petroleum-derived toxic organic solvents. Here we report, for the first time, the production of ethyl lactate directly from cellulose with the mesoporous Zr-SBA-15 silicate catalyst in a supercritical mixture of ethanol and water. The relatively strong Lewis and weak Bronsted acid sites on the catalyst, as well as the surface hydrophobicity, were beneficial to the reaction and led to synergy during consecutive reactions, such as depolymerization, retro-aldol condensation, and esterification. Under the optimum reaction conditions, ~33 % yield of ethyl lactate was produced from cellulose with the Zr-SBA-15 catalyst at 260 degrees C in supercritical 95:5 (w/w) ethanol/water. PMID- 26685116 TI - Comparison of respiratory health-related quality of life in patients with intractable breathlessness due to advanced cancer or advanced COPD. AB - OBJECTIVES: Breathlessness is common in patients with advanced cancer and almost universal in advanced chronic obstructive pulmonary disease (COPD), but studies suggest their experiences of breathlessness vary. This report builds on these studies by providing quantitative evidence of differences in respiratory health related quality of life (HRQoL) between these groups. Further, it explores the validity of the Chronic Respiratory Questionnaire (CRQ) in patients with cancer. METHODS: The CRQ-Original was completed within baseline interviews for a randomised controlled trial of a palliative intervention for intractable breathlessness due to advanced disease. Independent samples Mann-Whitney U tests were performed to identify significant differences in median scores for the four CRQ domains (mastery, dyspnoea, emotional function, fatigue) in patients with advanced COPD (n=73) or advanced cancer (n=67). The Minimally Clinically Important Difference of 0.5 was applied to determine clinical significance. RESULTS: Patients with advanced COPD scored lower across all four CRQ domains. This was statistically significant for dyspnoea, mastery and emotional function (p<0.05), and clinically significant for the latter two, suggesting poorer respiratory HRQoL. CONCLUSIONS: Patients with breathlessness due to advanced COPD have worse respiratory HRQoL than those with advanced cancer. This may result from greater burden of breathlessness in COPD due to condition longevity, lesser burden of breathlessness in cancer due to its episodic nature, or variance in palliative referral thresholds by disease group. Our results suggest that greater access to palliative care is needed in advanced COPD, and that formal psychometric testing of the CRQ may be warranted in cancer. TRIAL REGISTRATION NUMBER: NCT00678405. PMID- 26685117 TI - End-of-life experiences of mothers with advanced cancer: perspectives of widowed fathers. AB - OBJECTIVE: Despite the importance of parenting-related responsibilities for adult patients with terminal illnesses who have dependent children, little is known about the psychological concerns of dying parents and their families at the end of life (EOL). The aim of this study was to elicit widowed fathers' perspectives on how parental status may have influenced the EOL experiences of mothers with advanced cancer. SUBJECTS: 344 men identified themselves through an open-access educational website as widowed fathers who had lost a spouse to cancer and were raising dependent children. METHODS: Participants completed a web-based survey about their wife's EOL experience and cancer history, and their own depression (Center for Epidemiologic Studies Depression Scale, CES-D) and bereavement (Texas Revised Inventory of Grief, TRIG) symptoms. Descriptive statistics, Fisher's exact tests, and linear regression modelling were used to evaluate relationships between variables. RESULTS: According to fathers, 38% of mothers had not said goodbye to their children before death and 26% were not at all 'at peace with dying.' Ninety per cent of widowed fathers reported that their spouse was worried about the strain on their children at the EOL. Fathers who reported clearer prognostic communication between wife and physician had lower CES-D and TRIG scores. CONCLUSIONS: To improve EOL care for seriously ill patients and their families, we must understand the concerns of parents with dependent children. These data underscore the importance of parenting-related worries in this population and the need for additional clinical and research programmes devoted to addressing these issues. PMID- 26685118 TI - Microparticles manipulation and enhancement of their separation in pinched flow fractionation by insulator-based dielectrophoresis. AB - The separation and manipulation of microparticles in lab on a chip devices have importance in point of care diagnostic tools and analytical applications. The separation and sorting of particles from biological and clinical samples can be performed using active and passive techniques. In passive techniques, no external force is applied while in active techniques by applying external force (e.g. electrical), higher separation efficiency is obtained. In this article, passive (pinched flow fractionation) and active (insulator-based dielectrophoresis) methods were combined to increase the separation efficiency at lower voltages. First by simulation, appropriate values of geometry and applied voltages for better focusing, separation, and lower Joule heating were obtained. Separation of 1.5 and 6 MUm polystyrene microparticles was experimentally obtained at optimized geometry and low total applied voltage (25 V). Also, the trajectory of 1.5 MUm microparticles was controlled by adjusting the total applied voltage. PMID- 26685119 TI - The fate of mercury in municipal wastewater treatment plants in China: Significance and implications for environmental cycling. AB - Municipal wastewater treatment plants (WWTPs) play an important role in controlling pollutant discharges to surface waters. Previous studies suggested that the removal of mercury (Hg) by WWTPs was strongly correlated with solid removal. However, conclusions regarding possible transformations of Hg species within WWTPs were not consistent across those studies. We characterized total Hg (THg) and methylmercury (MeHg) concentrations and loads in a WWTP located in Jiaozuo, China, to further understand Hg fate and transformations in WWTPs. THg and MeHg were primarily associated with wastewater solids, and removal of both were greater than 90%; concentrations in the sewage were (2.0+/-2.7)*10(3)ng/L and 7.5+/-5.8ng/L, respectively. A mass balance calculation revealed that 80% of the THg input to the WWTP ended up in the sewage sludge (SS), while more than 70% of the influent MeHg mass was degraded, indicating WWTPs are an important sink for sewage-borne Hg. THg and MeHg concentrations in SS were (3.9+/-1.4)*10(3)ng/g and 6.3+/-2.3ng/g, respectively, suggesting SS could be a significant source of THg and MeHg to the environment if not handled properly. The significance of sewage and SS in the biogeochemical cycling of THg and MeHg in China is discussed. PMID- 26685115 TI - Association of High-Risk Human Papillomavirus with Genital Tract Mucosal Immune Factors in HIV-Infected Women. AB - PROBLEM: High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. METHOD OF STUDY: Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n = 8), other HR-HPV (n = 41), and non-HR-HPV controls (n = 79). RESULTS: Compared to controls, HR-HPV groups had higher plasma viral loads (P = 0.004), lower CD4 cells (P = 0.02), more genital tract HIV RNA (P = 0.03), greater number of different HPV types (P < 0.001), higher cervicovaginal lavage (CVL) IL-1alpha (P = 0.03) and human beta-defensin 2 (HBD2) (P = 0.049), and less anti-HIVB al activity (P = 0.03). HPV-16 remained significantly associated with higher HBD2 (P = 0.03), higher IL-1alpha (P = 0.009), and lower anti-HIVB aL activity (P = 0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. CONCLUSION: HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health. PMID- 26685120 TI - Spontaneous arsenic (III) oxidation with bioelectricity generation in single chamber microbial fuel cells. AB - Arsenic is one of the most toxic elements commonly found in groundwater. With initial concentration of 200MUgL(-1), spontaneous As(III) oxidation is realized completely during 7 days operation in single-chamber microbial fuel cells (MFCs) in the present study, with the maximum power density of 752.6+/-17mWm(-2). The product is less toxic and mobile As(V), which can be removed from aqueous solution more easily. High-throughput 16S rRNA gene pyrosequencing analysis indicates the existence of arsenic-resistant bacteria as Actinobacteria, Comamonas, Pseudomonas and arsenic-oxidizing bacteria as Enterobacter, with electrochemically active bacteria as Lactococcus, Enterobacter. They interact together and are responsible for As(III) oxidation and bioelectricity generation in MFCs. This study offers a potential attractive method for remediation of arsenic-polluted groundwater. PMID- 26685121 TI - Hybrid selective surface hydrophilization and froth flotation separation of hazardous chlorinated plastics from E-waste with novel nanoscale metallic calcium composite. AB - Treatment by a nanometallic Ca/CaO composite has been found to selectively hydrophilize the surface of polyvinyl chloride (PVC), enhancing its wettability and thereby promoting its separation from E-waste plastics by means of froth flotation. The treatment considerably decreased the water contact angle of PVC, by about 18 degrees . The SEM images of the PVC plastic after treatment displayed significant changes in their surface morphology compared to other plastics. The SEM-EDS results reveal that a markedly decrease of [Cl] concentration simultaneously with dramatic increase of [O] on the surface of the PCV samples. XPS results further confirmed an increase of hydrophilic functional groups on the PVC surface. Froth flotation at 100rpm mixing speed was found to be optimal, separating 100% of the PVC into a settled fraction of 96.4% purity even when the plastics fed into the reactor were of nonuniform size and shape. The total recovery of PVC-free plastics in E-waste reached nearly 100% in the floated fraction, significantly improved from the 20.5wt% of light plastics that can be recovered by means of conventional wet gravity separation. The hybrid method of nanometallic Ca/CaO treatment and froth flotation is effective in the separation of hazardous chlorinated plastics from E-waste plastics. PMID- 26685122 TI - Appropriate dosing of sugammadex to reverse deep rocuronium-induced neuromuscular blockade in morbidly obese patients. AB - In morbidly obese patients, the speed of reversal of neuromuscular blockade with sugammadex based on ideal body weight is still matter of debate. In this single center, randomised, double-blinded study, neuromuscular blockade was monitored in 50 patients using acceleromyography at the adductor pollicis. At the end of surgery with deep rocuronium-induced neuromuscular blockade, patients randomly received sugammadex 4 mg.kg(-1) (high dose group), 2 mg.kg(-1) (middle dose group), or 1 mg.kg(-1) (low dose group) of ideal body weight. After administration of the first dose of sugammadex, the mean (SD) recovery time (censored at 600 s) from deep neuromuscular blockade was significantly shorter (p < 0.001) in the high-dose group (n = 14; 255 (63) s) vs the middle-dose group (n = 13; 429 (102) s), or low-dose group (n = 4; 581 (154) s). Success rate from neuromuscular blockade reversal defined by a train-of-four >= 0.9 within 10 min after sugammadex administration, were 93%, 77% and 22% for these high, middle and low-dose groups respectively (p < 0.05 vs low-dose group). In morbidly obese patients, 4 mg.kg(-1) of ideal body weight of sugammadex allows suitable reversal of deep rocuronium-induced neuromuscular blockade. Monitoring remains essential to detect residual curarisation or recurarisation. PMID- 26685123 TI - Diet and Physical Activity in Rural vs Urban Children and Adolescents in the United States: A Narrative Review. AB - Current research suggests that the prevalence of obesity is higher among rural youth than urban youth. Due to the health implications that are associated with child and adolescent obesity, it is critical to understand systematic differences in diet and physical activity (PA) behaviors that may be contributing to this disparity in weight. However, varying definitions of rural and inconsistencies in study tools and methodologies may limit the generalizability of findings from research in this area. The objective of this narrative review was to synthesize and critically evaluate existing literature comparing diet and PA behaviors between rural and urban children and adolescents, providing recommendations for future research. Only five studies were found that reported on measures of diet in rural vs urban youth, whereas 16 were found that reported on measures of PA. Dietary assessment tools were generally standard and acceptable; however, differences existed in how dietary outcomes were defined. Few studies used assessment tools that objectively measured PA, and definitions for meeting PA recommendations varied among studies. Very few studies defined rural using the same criteria. Future research on the rural youth obesity disparity should focus on including a high-quality assessment of both diet and PA (as opposed to one or the other) and on using an appropriate and consistent definition of rural. PMID- 26685124 TI - Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. AB - Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated. PMID- 26685125 TI - A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment. AB - INTRODUCTION: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). METHODS: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. RESULTS: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). CONCLUSIONS: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. PMID- 26685126 TI - Analysis of Signaling Endosome Composition and Dynamics Using SILAC in Embryonic Stem Cell-Derived Neurons. AB - Neurons require efficient transport mechanisms such as fast axonal transport to ensure neuronal homeostasis and survival. Neurotrophins and their receptors are conveyed via fast axonal retrograde transport of signaling endosomes to the soma, where they elicit transcriptional responses. Despite the essential roles of signaling endosomes in neuronal differentiation and survival, little is known about their molecular identity, dynamics, and regulation. Gaining a better mechanistic understanding of these organelles and their kinetics is crucial, given the growing evidence linking vesicular trafficking deficits to neurodegeneration. Here, we exploited an affinity purification strategy using the binding fragment of tetanus neurotoxin (HCT) conjugated to monocrystalline iron oxide nanoparticles (MIONs), which in motor neurons, is transported in the same carriers as neurotrophins and their receptors. To quantitatively assess the molecular composition of HCT-containing signaling endosomes, we have developed a protocol for triple Stable Isotope Labeling with Amino acids in Cell culture (SILAC) in embryonic stem cell-derived motor neurons. After HCT internalization, retrograde carriers were magnetically isolated at different time points and subjected to mass-spectrometry and Gene Ontology analyses. This purification strategy is highly specific, as confirmed by the presence of essential regulators of fast axonal transport in the make-up of these organelles. Our results indicate that signaling endosomes undergo a rapid maturation with the acquisition of late endosome markers following a specific time-dependent kinetics. Strikingly, signaling endosomes are specifically enriched in proteins known to be involved in neurodegenerative diseases and neuroinfection. Moreover, we highlighted the presence of novel components, whose precise temporal recruitment on signaling endosomes might be essential for proper sorting and/or transport of these organelles. This study provides the first quantitative proteomic analysis of signaling endosomes isolated from motor neurons and allows the assembly of a functional map of these axonal carriers involved in long-range neuronal signaling. PMID- 26685128 TI - White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging. AB - Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 * 106, n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats. PMID- 26685127 TI - Identification of the Post-translational Modifications Present in Centromeric Chromatin. AB - The centromere is the locus on the chromosome that acts as the essential connection point between the chromosome and the mitotic spindle. A histone H3 variant, CENP-A, defines the location of the centromere, but centromeric chromatin consists of a mixture of both CENP-A-containing and H3-containing nucleosomes. We report a surprisingly uniform pattern of primarily monomethylation on lysine 20 of histone H4 present in short polynucleosomes mixtures of CENP-A and H3 nucleosomes isolated from functional centromeres. Canonical H3 is not a component of CENP-A-containing nucleosomes at centromeres, so the H3 we copurify from these preparations comes exclusively from adjacent nucleosomes. We find that CENP-A-proximal H3 nucleosomes are not uniformly modified but contain a complex set of PTMs. Dually modified K9me2-K27me2 H3 nucleosomes are observed at the centromere. Side-chain acetylation of both histone H3 and histone H4 is low at the centromere. Prior to assembly at centromeres, newly expressed CENP-A is sequestered for a large portion of the cell cycle (late S-phase, G2, and most of mitosis) in a complex that contains its partner, H4, and its chaperone, HJURP. In contrast to chromatin associated centromeric histone H4, we show that prenucleosomal CENP-A-associated histone H4 lacks K20 methylation and contains side-chain and alpha-amino acetylation. We show HJURP displays a complex set of serine phosphorylation that may potentially regulate the deposition of CENP-A. Taken together, our findings provide key information regarding some of the key components of functional centromeric chromatin. PMID- 26685130 TI - Transporting STEMI patients for primary PCI: a long and winding road paved with good intentions? PMID- 26685129 TI - Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo. AB - AIMS: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. METHODS AND RESULTS: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 * 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11 CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 +/- 9.5% of DES and 55.8 +/- 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 +/- 10.6% (DES) and 5.1 +/- 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). CONCLUSION: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing. PMID- 26685131 TI - Live-case demonstrations: putting patients first. AB - Live-case demonstrations have become essential teaching tools. Debate about their added educational value and risk-benefit considerations vis-a-vis patient safety demand that major interventional cardiology meetings offering live-case demonstrations carefully define and monitor the objectives and quality of the cases included at their meetings. To this end, Europa Organisation, the content providing group that supports EuroPCR and other PCR conferences internationally, has convened the PCR VITAL-Live Workshop, bringing together senior interventional cardiologists and experienced live-case operators with the aim of defining and reviewing the key components and goals of valuable live-case demonstrations. The Vital-Live participants unanimously agreed that live cases provide an educational experience with an immediacy and intensity that is unmatched by taped cases, through audience engagement with unfiltered reality and participation in real time decision-making. Best practices regarding case selection, preparation, objectives, delivery, and discussion of the demonstrations were designed to ensure that the lessons learned would be clear and implementable by audience members, leading to improved patient care and safety in their own practices. Today's on-line accessibility of live-cases underscores the need for operators, hospitals, panels, and meeting chairs to insure that the content, quality, and intent anticipate any public scrutiny. This requires putting patient outcomes first, both at the level of the live demonstration itself and its broader educational worth. PMID- 26685132 TI - Tetralogy of Fallot, pulmonary valve replacement, and right ventricular volumes: are we chasing the right target? PMID- 26685133 TI - Bivalirudin, glycoprotein inhibitor, and heparin use and association with outcomes of primary percutaneous coronary intervention in the United Kingdom. AB - AIMS: The HORIZONS trial reported a survival advantage for bivalirudin over heparin-with-glycoprotein inhibitors (GPIs) in primary PCI for ST elevation myocardial infarction. This drove an international shift in clinical practice. Subsequent studies have produced divergent findings on mortality benefits with bivalirudin. We investigated this issue in a larger population than studied in any of these trials, using the United Kingdom national PCI registry. METHODS AND RESULTS: 61 136 primary PCI procedures were performed between January 2008 and January 2012. Demographic and procedural data were obtained from the registry. Mortality information was obtained through the UK Office of National Statistics. Multivariable logistic regression and propensity analysis modelling were utilized to study the association of different anti-thrombotic strategies with outcomes. Unadjusted data demonstrated near-identical survival curves for bivalirudin and heparin-plus-GPI groups. Significantly higher early and late mortality was found in patients treated with heparin alone ( ITALIC! P < 0.0001) but this group had a markedly higher baseline risk. After propensity matching, the bivalirudin vs. heparin-plus-GPI groups still demonstrated very similar adjusted mortality (odds ratio 1.00 at 30 days, and 0.96 at 1 year). Patients treated with heparin alone continued to show higher mortality after adjustment, although effect size was considerably diminished (odds ratio vs. other groups 1.17-1.24 at 30 days). CONCLUSIONS: Analysis of recent UK data showed no significant difference in short or medium-term mortality between ST elevation myocardial infarction patients treated with bivalirudin vs. heparin-plus-GPI at primary PCI. PMID- 26685134 TI - Cardiac surgery during the acute phase of infective endocarditis: discrepancies between European Society of Cardiology guidelines and practices. AB - AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients. PMID- 26685135 TI - Choosing a perspective on mortality with DAPT. PMID- 26685136 TI - Risk stratification of patients undergoing medical therapy after coronary angiography. AB - AIM: We sought to investigate the prognostic impact of the SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) score (SS) on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) undergoing medical therapy only. METHODS AND RESULTS: Among the 13 819 patients enrolled in the ACUITY trial and undergoing coronary angiogram, 4491 patients were treated with medical therapy as the initial strategy. Of those, baseline SS and complete angiographic analysis were available in 1275 patients. Patients were divided in four groups based on the presence or absence of coronary artery disease (CAD) and subsequently, among patients with CAD, by SS. Major adverse cardiac events (MACE) and its individual components (death, myocardial infarction, and unplanned revascularization) were compared between groups. Among the 1275 patients, the mean SS was 3.5 +/- 7.0 (range 0-45). SYNTAX score was 0 in 842 patients, >0 and <=5 in 170, >5 and <=11 in 119, and >11 in 144 patients. The 1-year rates of MACE were higher in patients with CAD and higher SS. By multivariable analysis, the SS was a strong predictor of all adverse ischaemic events, including mortality. By receiver operator characteristic analysis, an SS cut-off of 8 showed the best prognostic accuracy for death and MACE. CONCLUSION: In patients with NSTE ACS undergoing medical therapy, the SS, especially when >8, was shown to be a strong predictor of 1-year MACE, including mortality. This finding has important clinical implications for risk stratification of patients with NSTE ACS undergoing medical therapy after an initial angiogram. PMID- 26685137 TI - Optical coherence tomography-guided percutaneous coronary intervention in pre terminal chronic kidney disease with no radio-contrast administration. PMID- 26685138 TI - Bullet incarcerated in aortic root. PMID- 26685139 TI - When the money is not in the bank. PMID- 26685140 TI - Left ventricular systolic function assessment in secondary mitral regurgitation: left ventricular ejection fraction vs. speckle tracking global longitudinal strain. AB - AIMS: Left ventricular (LV) ejection fraction (LVEF) is currently considered for the decision making of patients with mitral regurgitation (MR). However, LVEF represents change in LV volume between end-diastole and end-systole but does not characterize the intrinsic function of the myocardium. In contrast, speckle tracking global longitudinal strain (GLS) characterizes myocardial deformation. The present study evaluated whether LV GLS may detect further impairment in LV systolic function in dilated cardiomyopathy patients with and without severe secondary MR matched based on LVEF. METHODS AND RESULTS: Patients with non ischaemic dilated cardiomyopathy (N = 150, 59 +/- 12 years old, 58% male) were included: 75 patients with severe secondary MR and 75 patients with none or less than mild MR matched 1 : 1 according to LVEF. The LV systolic function was evaluated by LVEF (following Simpson's biplane method), forward ejection fraction (forward stroke volume relative to LV end-diastolic volume), and speckle-tracking GLS. By definition, LVEF was comparable between the two groups (patients with severe MR 31 +/- 10 vs. patients with no/mild MR 31 +/- 10%, P = 0.93). However, patients with severe MR had significantly lower forward ejection fraction (29 +/- 14 vs. 40 +/- 18%, P < 0.001) and more impaired GLS (-8.08 +/- 3.33 vs. -9.78 +/- 3.78%, P = 0.004) compared with their counterparts. The presence of severe secondary MR was significantly associated with worse LV GLS (beta 1.32, 95% confidence interval 0.14-2.49, P = 0.03). CONCLUSION: In patients with severe secondary MR, speckle-tracking GLS shows more deteriorated LV systolic function than LVEF. PMID- 26685141 TI - Non-Hodgkin lymphoma and idiopathic inflammatory cardiomyopathy. PMID- 26685142 TI - Blood pressure target values: the saga continues. PMID- 26685143 TI - A rare case of giant left atrium in a child. PMID- 26685144 TI - How can the European Society of Cardiology ensure compliance with ethical standards? PMID- 26685145 TI - Aortic valve replacement in younger adults: a biological valve is not the logical choice. PMID- 26685146 TI - Perceptions, attitude and uptake of rapid syphilis testing services in antenatal clinics in North-Western Tanzania. AB - Infection with syphilis during pregnancy could cause spontaneous abortion, low birth weight and stillbirth. To prevent adverse pregnancy outcomes caused by syphilis, the World Health Organization (WHO) recommends syphilis screening and treatment of all pregnant women attending antenatal care (ANC) services. Rapid syphilis testing (RST) demonstration project was introduced at ANC clinics in Tanzania in 2009, to assess the feasibility, acceptability and its impact on uptake of syphilis screening service. Data collection was composed of in-depth interviews with health workers and pregnant women attending ANC. Additionally, from the health facility registers we extracted information on the uptake of antenatal care services, including number of pregnant women screened and treated for syphilis. Introduction of RST at health facilities was appreciated by pregnant women attending ANC and health workers. Following the introduction of RST services at ANC clinics, we observed a significant increase of the uptake of syphilis screening. Pregnant women appreciated RST service since it reduced the frequency of their visits to the health facilities and shortened the duration that they spent at the clinics. Moreover, the provision of same-day screening and treatment services helped women to save money that they would have to spend on transportation for the follow up visits. Health workers felt that RST simplified procedures to diagnose syphilis, and enabled the health workers to test and treat large numbers of clients in a shorter period of time. Our study demonstrates that, it is feasible to introduce RST service in antenatal clinics. The RST was appreciated by health workers and pregnant women, since it simplifies syphilis screening procedures, saves the time that pregnant women used to waste to wait for the results, and saves the cost that women would have to spend on transportation to come back for treatment. PMID- 26685147 TI - Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study. AB - Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects. PMID- 26685148 TI - Human factors in healthcare: welcome progress, but still scratching the surface. PMID- 26685149 TI - Not so new directions in the law of consent? Examining Montgomery v Lanarkshire Health Board. AB - This paper examines the UK Supreme Court decision in Montgomery v Lanarkshire Health Board, which deals with consent and information disclosure in medical treatment and care. It signaled a move away from a 'doctor knows best' approach to one that focuses on disclosing information to which particular patients would attach significance. Notwithstanding concerns about increased litigation and loss of professional autonomy, the reality is that the decision will make little difference to healthcare practice and consent in the UK. The Supreme Court has endorsed a view that most lawyers and doctors thought already prevailed, and it reflects the General Medical Council's guidance on the issue of consent in any case. Given recent healthcare scandals in the National Health Service (NHS), the Supreme Court's legal recognition of the importance of recognizing patient autonomy in disclosing risks about medical treatment and care is a welcome development. PMID- 26685150 TI - Harm isn't all you need: parental discretion and medical decisions for a child. PMID- 26685151 TI - Iron-dependent gene expression in Actinomyces oris. AB - BACKGROUND: Actinomyces oris is a Gram-positive bacterium that has been associated with healthy and diseased sites in the human oral cavity. Most pathogenic bacteria require iron to survive, and in order to acquire iron in the relatively iron-scarce oral cavity A. oris has been shown to produce iron-binding molecules known as siderophores. The genes encoding these siderophores and transporters are thought to be regulated by the amount of iron in the growth medium and by the metal-dependent repressor, AmdR, which we showed previously binds to the promoter of proposed iron-regulated genes. OBJECTIVE: The purpose of this study was to characterize siderophore and associated iron transport systems in A. oris. DESIGN: We examined gene expression of the putative iron transport genes fetA and sidD in response to low- and high-iron environments. One of these genes, sidD, encoding a putative Fe ABC transporter protein, was insertionally inactivated and was examined for causing growth defects. To gain a further understanding of the role of iron metabolism in oral diseases, clinical isolates of Actinomyces spp. were examined for the presence of the gene encoding AmdR, a proposed global regulator of iron-dependent gene expression in A. oris. RESULTS: When A. oris was grown under iron-limiting conditions, the genes encoding iron/siderophore transporters fetA and sidD showed increased expression. One of these genes (sidD) was mutated, and the sidD::Km strain exhibited a 50% reduction in growth in late log and stationary phase cells in media that contained iron. This growth defect was restored when the sidD gene was provided in a complemented strain. We were able to isolate the AmdR-encoding gene in seven clinical isolates of Actinomyces. When these protein sequences were aligned to the laboratory strain, there was a high degree of sequence similarity. CONCLUSIONS: The growth of the sidD::Km mutant in iron-replete medium mirrored the growth of the wild type strain grown in iron-limiting medium, suggesting that the sidD::Km mutant was compromised in iron uptake. The known iron regulator AmdR is well conserved in clinical isolates of A. oris. This work provides additional insight into iron metabolism in this important oral microbe. PMID- 26685152 TI - Surgical repair of partial atrioventricular defect. AB - Long-term survival rate of patients operated for partial atrioventricular (AV) canal is lower than that of the general population, and late complications are relatively significant: between 10 and 30% of operated patients present with left AV valve regurgitation, and up to 25% have to be reoperated for valve repair or replacement, left ventricular outflow tract obstruction or residual atrial septal defect. Because the left AV valve regurgitation is the most common complication following surgery, technical details in the surgical management of the mitral valve are the most important aspects of this procedure; for example, the decision to close the cleft and to perform an annuloplasty. The presence of mitral valve anomalies in 7-28% of the cases complicates further the surgical management of these valves. This article will describe in detail the operative technique of partial AV canal repair, and review the relevant literature. PMID- 26685153 TI - Histological assessment of the triangular fibrocartilage complex. AB - The morphological structure of the seven components of triangular fibrocartilage complexes of 11 cadaver wrists of elderly people was assessed microscopically, after staining with Hematoxylin-Eosin and Elastica van Gieson. The articular disc consisted of tight interlaced fibrocartilage without blood vessels except in its ulnar part. Volar and dorsal radioulnar ligaments showed densely parallel collagen bundles. The subsheath of the extensor carpi ulnaris muscle, the ulnotriquetral and ulnolunate ligament showed mainly mixed tight and loose parallel tissue. The ulnolunate ligament contained tighter parallel collagen bundles and clearly less elastic fibres than the ulnotriquetral ligament. The ulnocarpal meniscoid had an irregular morphological composition and loose connective tissue predominated. The structure of the articular disc indicates a buffering function. The tight structure of radioulnar and ulnolunate ligaments reflects a central stabilizing role, whereas the ulnotriquetral ligament and ulnocarpal meniscoid have less stabilizing functions. PMID- 26685154 TI - Inter- and intra-tester reliability of sensibility testing in digital nerve repair. AB - The aim of this study was to investigate the inter- and intra-tester reliability of the static two-point discrimination and Semmes-Weinstein monofilament tests in digital nerve repair. A total of 100 digital nerves from 67 patients were included into the study. An experienced orthopaedic surgeon and a physiotherapist examined the sensory nerve recovery. The reproducibility score of both tests was at a poor level, but the reliability of the Semmes-Weinstein monofilament test was higher than the static two-point discrimination test. These tests should not be used alone in the quantitative monitoring of sensory recovery, but should be interpreted with the clinical findings.Level 3 non-randomized controlled study. PMID- 26685155 TI - Dopamine selectively remediates 'model-based' reward learning: a computational approach. AB - Patients with loss of dopamine due to Parkinson's disease are impaired at learning from reward. However, it remains unknown precisely which aspect of learning is impaired. In particular, learning from reward, or reinforcement learning, can be driven by two distinct computational processes. One involves habitual stamping-in of stimulus-response associations, hypothesized to arise computationally from 'model-free' learning. The other, 'model-based' learning, involves learning a model of the world that is believed to support goal-directed behaviour. Much work has pointed to a role for dopamine in model-free learning. But recent work suggests model-based learning may also involve dopamine modulation, raising the possibility that model-based learning may contribute to the learning impairment in Parkinson's disease. To directly test this, we used a two-step reward-learning task which dissociates model-free versus model-based learning. We evaluated learning in patients with Parkinson's disease tested ON versus OFF their dopamine replacement medication and in healthy controls. Surprisingly, we found no effect of disease or medication on model-free learning. Instead, we found that patients tested OFF medication showed a marked impairment in model-based learning, and that this impairment was remediated by dopaminergic medication. Moreover, model-based learning was positively correlated with a separate measure of working memory performance, raising the possibility of common neural substrates. Our results suggest that some learning deficits in Parkinson's disease may be related to an inability to pursue reward based on complete representations of the environment. PMID- 26685156 TI - Neural bases of orthographic long-term memory and working memory in dysgraphia. AB - Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills. PMID- 26685157 TI - Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy. AB - Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease. PMID- 26685158 TI - Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target. AB - Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of alpha1 receptor subunit containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. PMID- 26685159 TI - Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome. AB - Smith-Lemli-Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7 dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID- 26685162 TI - Modern radiology and the use of resources. Too much technology (?) - Not at all. PMID- 26685160 TI - The apical ectodermal ridge of the mouse model of ectrodactyly Dlx5;Dlx6-/- shows altered stratification and cell polarity, which are restored by exogenous Wnt5a ligand. AB - The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5-DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double knockout (DKO) of Dlx5 and Dlx6. During limb development, the apical ectodermal ridge (AER) is a key-signaling center responsible for early proximal-distal growth and patterning. In Dlx5;6 DKO hindlimbs, the central wedge of the AER loses multilayered organization and shows down-regulation of FGF8 and Dlx2. In search for the mechanism, we examined the non-canonical Wnt signaling, considering that Dwnt-5 is a target of distalless in Drosophila and the knockout of Wnt5, Ryk, Ror2 and Vangl2 in the mouse causes severe limb malformations. We found that in Dlx5;6 DKO limbs, the AER expresses lower levels of Wnt5a, shows scattered beta-catenin responsive cells and altered basolateral and planar cell polarity (PCP). The addition of Wnt5a to cultured embryonic limbs restored the expression of AER markers and its stratification. Conversely, the inhibition of the PCP molecule c-jun N-terminal kinase caused a loss of AER marker expression. In vitro, the addition of Wnt5a on mixed primary cultures of embryonic ectoderm and mesenchyme was able to confer re-polarization. We conclude that the Dlx related ectrodactyly defect is associated with the loss of basoapical and PCP, due to reduced Wnt5a expression and that the restoration of the Wnt5a level is sufficient to partially reverts AER misorganization and dysmorphology. PMID- 26685161 TI - Accumulated Metabolites of Hydroxybutyric Acid Serve as Diagnostic and Prognostic Biomarkers of Ovarian High-Grade Serous Carcinomas. AB - Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but it is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID- 26685163 TI - Classic papers from the Acta Radiologica archives. PMID- 26685164 TI - Editorial. PMID- 26685165 TI - On the X-ray Diagnosis of Gallstones in the Common Duct. PMID- 26685167 TI - Hindlimb muscle fibre size and glycogen stores in bank voles with increased aerobic exercise metabolism. AB - To test hypotheses concerning physiological factors limiting the rate of aerobic exercise metabolism, we used a unique experimental evolution model: lines of bank voles selected for high swim-induced aerobic metabolism (A) and unselected, control lines (C). We investigated putative adaptations that result in the increased performance of the hindlimb muscle (gastrocnemius joined with plantaris). The body mass-adjusted muscle mass was higher in A-lines (0.093 g) than in C-lines (0.083 g; P=0.01). However, selection did not affect mean muscle fibre cross-sectional area (P=0.34) or glycogen content assessed with a histochemical periodic acid-Schiff reaction (PAS; P=0.82). The results suggest that the increased aerobic performance is achieved by an increase of total muscle mass, without major qualitative changes in the muscle fibre architecture. However, such a conclusion should be treated with caution, because other modifications, such as increased density of capillaries or mitochondria, could occur. PMID- 26685168 TI - Salt sensitivity of the morphometry of Artemia franciscana during development: a demonstration of 3D critical windows. AB - A 3D conceptual framework of 'critical windows' was used to examine whether the morphometry of Artemia franciscana is altered by salinity exposure during certain key periods of development. Artemia franciscana were hatched at 20 ppt (designated control salinity) and were then exposed to 10, 30, 40 or 50 ppt either chronically (days 1-15) or only on days 1-6, 7-9, 10-12 or 13-15. On day 15, maturity was assessed and morphometric characteristics, including mass, total body length, tail length and width, length of the third swimming appendage and eye diameter, were measured. Maturation and morphometry on day 15 were influenced by the exposure window and salinity dose. Artemia franciscana were generally larger following exposure to 10 and 40 ppt during days 1-6 and 7-9 when compared with days 10-12 and 13-15, in part due to a higher percentage of mature individuals. Exposure to different salinities on days 1-6 produced the greatest differences in morphometry, and thus this appears to be a period in development when A. franciscana is particularly sensitive to salinity. Viewing the developmental window as three-dimensional allowed more effective visualization of the complex interactions between exposure window, stressor dose and the magnitude of morphometric changes in A. franciscana. PMID- 26685169 TI - Developmentally arrested Austrofundulus limnaeus embryos have changes in post translational modifications of histone H3. AB - Although vertebrate embryogenesis is typically a continuous and dynamic process, some embryos have evolved mechanisms to developmentally arrest. The embryos of Austrofundulus limnaeus, a killifish that resides in ephemeral ponds, routinely enter diapause II (DII), a reversible developmental arrest promoted by endogenous cues rather than environmental stress. DII, which starts at 24-26 days post fertilization and can persist for months, is characterized by a significant decline in heart rate and an arrest of development and differentiation. Thus, A. limnaeus is a unique model to study epigenetic features associated with embryonic arrest. To investigate chromosome structures associated with mitosis or gene expression, we examined the post-translational modifications of histone H3 (phosphorylation of serine 10, mono-, di- and tri-methylation of lysine 4 or 27) in preDII, DII and postDII embryos. As seen by microscopy analysis, DII embryos have a significant decrease in the H3S10P marker for mitotic nuclei and an inner nuclear membrane localization of the H3K27me2 marker associated with silencing of gene expression. ELISA experiments reveal that the levels of methylation at H3K4 and H3K27 are significantly different between preDII, DII and postDII embryos, indicating that there are molecular differences between embryos of different chronological age and stage of development. Furthermore, in DII embryos relative to preDII embryos, there are differences in the level of H3K27me3 and H3K4me3, which may reflect critical chromatin remodeling that occurs prior to arrest of embryogenesis. This work helps lay a foundation for chromatin analysis of vertebrate embryo diapause, an intriguing yet greatly understudied phenomenon. PMID- 26685170 TI - Friends with benefits: the role of huddling in mixed groups of torpid and normothermic animals. AB - Huddling and torpor are widely used for minimizing heat loss by mammals. Despite the questionable energetic benefits from social heterothermy of mixed groups of warm normothermic and cold torpid individuals, the heterothermic Australian sugar glider (Petaurus breviceps) rests in such groups during the cold season. To unravel why they might do so, we examined torpor expression of two sugar glider groups of four individuals each in outside enclosures during winter. We observed 79 torpor bouts during 50 days of observation and found that torpor bouts were longer and deeper when all individuals of a group entered torpor together, and therefore infer that they would have saved more energy in comparison to short and shallow solitary torpor bouts. However, all gliders of either group only expressed torpor uniformly in response to food restriction, whereas on most occasions at least one individual per group remained normothermic. Nevertheless, the presence of warm gliders in mixed groups also appears to be of energetic advantage for torpid individuals, because nest box temperature was negatively correlated with the number of torpid gliders, and normothermic individuals kept the nest temperature at a value closer to the threshold for thermoregulatory heat production during torpor. Our study suggests that mixed groups of torpid and normothermic individuals are observed when environmental conditions are adverse but food is available, leading to intermediate energy savings from torpor. However, under especially challenging conditions and when animals are starving, energy savings are maximized by uniform and pronounced expression of torpor. PMID- 26685171 TI - Temperature experienced during incubation affects antioxidant capacity but not oxidative damage in hatchling red-eared slider turtles (Trachemys scripta elegans). AB - Our understanding of how oxidative stress resistance phenotypes are affected by the developmental environment is limited. One component of the developmental environment, which is likely central to early life oxidative stress among ectothermic and oviparous species, is that of temperature. We investigated how incubation temperature manipulations affect oxidative damage and total antioxidant capacity (TAC) in red-eared slider turtle (Trachemys scripta elegans) hatchlings. First, to determine whether temperature fluctuations elicit oxidative stress, eggs from clutches were randomly assigned to either a constant (29.5 degrees C) or daily fluctuating temperature incubation (28.7 +/- 3 degrees C) treatment. Second, to assess the effect of temperature fluctuation frequency on oxidative stress, eggs were incubated in one of three fluctuating incubation regimes: 28.7 +/- 3 degrees C fluctuations every 12 h (hyper), 24 h (normal) or 48 h (hypo). Third, we tested the influence of average incubation temperature by incubating eggs in a daily fluctuating incubation temperature regime with a mean temperature of 26.5 degrees C (low), 27.1 degrees C (medium) or 27.7 degrees C (high). Although the accumulation of oxidative damage in hatchlings was unaffected by any thermal manipulation, TAC was affected by both temperature fluctuation frequency and average incubation temperature. Individuals incubated with a low frequency of temperature fluctuations had reduced TAC, while incubation at a lower average temperature was associated with enhanced TAC. These results indicate that although sufficient to prevent oxidative damage, TAC is influenced by developmental thermal environments, potentially because of temperature-mediated changes in metabolic rate. The observed differences in TAC may have important future consequences for hatchling fitness and overwinter survival. PMID- 26685172 TI - The role of human ankle plantar flexor muscle-tendon interaction and architecture in maximal vertical jumping examined in vivo. AB - Humans utilise elastic tendons of lower limb muscles to store and return energy during walking, running and jumping. Anuran and insect species use skeletal structures and/or dynamics in conjunction with similarly compliant structures to amplify muscle power output during jumping. We sought to examine whether human jumpers use similar mechanisms to aid elastic energy usage in the plantar flexor muscles during maximal vertical jumping. Ten male athletes performed maximal vertical squat jumps. Three-dimensional motion capture and a musculoskeletal model were used to determine lower limb kinematics that were combined with ground reaction force data in an inverse dynamics analysis. B-mode ultrasound imaging of the lateral gastrocnemius (GAS) and soleus (SOL) muscles was used to measure muscle fascicle lengths and pennation angles during jumping. Our results highlighted that both GAS and SOL utilised stretch and recoil of their series elastic elements (SEEs) in a catapult-like fashion, which likely serves to maximise ankle joint power. The resistance of supporting of body weight allowed initial stretch of both GAS and SOL SEEs. A proximal-to-distal sequence of joint moments and decreasing effective mechanical advantage early in the extension phase of the jumping movement were observed. This facilitated a further stretch of the SEE of the biarticular GAS and delayed recoil of the SOL SEE. However, effective mechanical advantage did not increase late in the jump to aid recoil of elastic tissues. PMID- 26685173 TI - Metabolite profiling of symbiont and host during thermal stress and bleaching in a model cnidarian-dinoflagellate symbiosis. AB - Bleaching (dinoflagellate symbiont loss) is one of the greatest threats facing coral reefs. The functional cnidarian-dinoflagellate symbiosis, which forms coral reefs, is based on the bi-directional exchange of nutrients. During thermal stress this exchange breaks down; however, major gaps remain in our understanding of the roles of free metabolite pools in symbiosis and homeostasis. In this study we applied gas chromatography-mass spectrometry (GC-MS) to explore thermally induced changes in intracellular pools of amino and non-amino organic acids in each partner of the model sea anemone Aiptasia sp. and its dinoflagellate symbiont. Elevated temperatures (32 degrees C for 6 days) resulted in symbiont photoinhibition and bleaching. Thermal stress induced distinct changes in the metabolite profiles of both partners, associated with alterations to central metabolism, oxidative state, cell structure, biosynthesis and signalling. Principally, we detected elevated pools of polyunsaturated fatty acids (PUFAs) in the symbiont, indicative of modifications to lipogenesis/lysis, membrane structure and nitrogen assimilation. In contrast, reductions of multiple PUFAs were detected in host pools, indicative of increased metabolism, peroxidation and/or reduced translocation of these groups. Accumulations of glycolysis intermediates were also observed in both partners, associated with photoinhibition and downstream reductions in carbohydrate metabolism. Correspondingly, we detected accumulations of amino acids and intermediate groups in both partners, with roles in gluconeogenesis and acclimation responses to oxidative stress. These data further our understanding of cellular responses to thermal stress in the symbiosis and generate hypotheses relating to the secondary roles of a number of compounds in homeostasis and heat-stress resistance. PMID- 26685174 TI - Lingual articulation in songbirds. AB - Lingual articulation in humans is one of the primary means of vocal tract resonance filtering that produces the characteristic vowel formants of speech. In songbirds, the function of the tongue in song has not been thoroughly examined, although recent research has identified the oropharyngeal-esophageal cavity as a resonance filter that is actively tuned to the frequency of the song. In northern cardinals (Cardinalis cardinalis), the volume of this cavity is inversely proportional to the frequency of the song above 2 kHz. However, cardinal song extends below this range, leaving the question of whether and how the vocal tract is tracking these low frequencies. We investigated the possible role of the tongue in vocal tract filtering using X-ray cineradiography of northern cardinals. Below 2 kHz, there was prominent tongue elevation in which the tip of the tongue was raised until it seemed to touch the palate. These results suggest that tongue elevation lowers the resonance frequency below 2 kHz by reducing the area of the passage from the oral cavity into the beak. This is consistent with a computational model of the songbird vocal tract in which resonance frequencies are actively adjusted by both changing the volume of the oropharyngeal-esophageal cavity and constricting the opening into the beak. PMID- 26685175 TI - Predicting the Human Genome Using Evolution. PMID- 26685177 TI - Strong Maternal Effects on Gene Expression in Arabidopsis lyrata Hybrids. AB - Hybridization between populations or species can have pronounced fitness consequences. Yet little is known about how hybridization affects gene regulation. Three main models have been put forward to explain gene expression patterns in hybrids: additive, dominance, or parental effects. Here, we use high throughput RNA-sequencing to examine the extent to which hybrid gene expression follows predictions by each of the three models. We performed a reciprocal crossing experiment between two differentiated populations of the perennial herb Arabidopsis lyrata and sequenced RNA in rosette leaves of 12-week-old plants grown in greenhouse conditions. The two parental populations had highly differentiated gene expression patterns. In hybrids, a majority of genes showed intermediate expression relative to that of their parental populations (i.e., additive effects), but expression was frequently more similar to the maternal than to their paternal population (i.e., maternal effects). Allele-specific expression analyses showed that in the vast majority of cases, genes with pronounced maternal effect expressed both the maternal and the paternal allele. Maternal effects on hybrid gene expression have rarely been documented previously and our study suggests it could be more common than previously assumed. Whether the maternal effect on gene expression persists to later life-stages, and whether the variation in gene expression is manifested in other aspects of the phenotype, remain to be elucidated. Our findings are relevant for understanding the consequences of outbreeding and hybridization and open up several questions for future studies. PMID- 26685176 TI - VHICA, a New Method to Discriminate between Vertical and Horizontal Transposon Transfer: Application to the Mariner Family within Drosophila. AB - Transposable elements (TEs) are genomic repeated sequences that display complex evolutionary patterns. They are usually inherited vertically, but can occasionally be transmitted between sexually independent species, through so called horizontal transposon transfers (HTTs). Recurrent HTTs are supposed to be essential in life cycle of TEs, which are otherwise destined for eventual decay. HTTs also impact the host genome evolution. However, the extent of HTTs in eukaryotes is largely unknown, due to the lack of efficient, statistically supported methods that can be applied to multiple species sequence data sets. Here, we developed a new automated method available as a R package "vhica" that discriminates whether a given TE family was vertically or horizontally transferred, and potentially infers donor and receptor species. The method is well suited for TE sequences extracted from complete genomes, and applicable to multiple TEs and species at the same time. We first validated our method using Drosophila TE families with well-known evolutionary histories, displaying both HTTs and vertical transmission. We then tested 26 different lineages of mariner elements recently characterized in 20 Drosophila genomes, and found HTTs in 24 of them. Furthermore, several independent HTT events could often be detected within the same mariner lineage. The VHICA (Vertical and Horizontal Inheritance Consistence Analysis) method thus appears as a valuable tool to analyze the evolutionary history of TEs across a large range of species. PMID- 26685178 TI - CHA2DS2-VASc Score is a Predictor of No-Reflow in Patients With ST-Segment Elevation Myocardial Infarction Who Underwent Primary Percutaneous Intervention. AB - Thrombosis and distal embolization play crucial role in the etiology of no reflow. CHA2DS2-VASc score is used to estimate the risk of thromboembolism in patients with atrial fibrillation. We tested the hypothesis that CHA2DS2-VASc can predict no-reflow among patients who underwent primary percutaneous coronary intervention (PCI). A total number of 2375 consecutive patients with ST-segment elevation myocardial infarction were assessed for the study. Patients were divided into 2 groups as no-reflow (n = 111) and control (n = 1670) groups according to post-PCI no-reflow status. CHA2DS2-VASc scores were calculated for all patients. CHA2DS2-VASc scores were significantly higher in the no-reflow group compared to the control group. After a multivariate regression analysis, CHA2DS2-VASc score remained as an independent predictor (odds ratio: 1.58, 95% confidence interval: 1.33-1,88, P < .001) of no-reflow. Receiver-operating characteristics analysis revealed the cutoff value of CHA2DS2-VASc score >=2 as a predictor of no-reflow with a sensitivity of 66% and a specificity of 59%. Moreover, in-hospital mortality was also associated with significantly higher CHA2DS2-VASc scores. In conclusion, CHA2DS2-VASc score is associated with higher risk of no-reflow and in-hospital mortality rates in patients who underwent primary PCI. PMID- 26685179 TI - Red Cell Distribution Width and Contrast-Induced Nephropathy. PMID- 26685180 TI - Relationship of Endothelial Cell-Specific Molecule 1 Level in Stress Hyperglycemia Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pilot Study. AB - Endothelial cell-specific molecule 1 ([ESM-1], endocan) is a new biomarker of endothelial dysfunction, which may be involved in the pathogenesis of atherosclerosis and stress hyperglycemia in patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated serum ESM-1 levels in patients with stress hyperglycemia having STEMI; 105 patients with STEMI and 33 individuals as a control group were included in the study. The patients were followed up for 3 months and major adverse cardiac events (MACEs) were recorded. Serum ESM-1 level was significantly higher in patients with stress hyperglycemia patients having STEMI (P < .05). In these patients, serum ESM-1 levels correlated positively with glucose levels (r = .21, P < .05). Multiple factor logistic regression analysis showed that serum ESM-1 levels >1.01 ng/mL (odds ratio 3.01, 95% confidence interval 1.05-8.64, P < .05) were an independent predictor of MACEs. Our findings suggest that ESM-1 is a novel biomarker overexpressed in patients with stress hyperglycemia having STEMI, admission glucose levels are associated with ESM-1 levels, and ESM-1 is an independent predictor of MACEs. An ESM-1 level >1.01 ng/mL is likely to predict a greater risk of MACEs. PMID- 26685181 TI - The Impact of Hypoglycemia on the Cardiovascular System: Physiology and Pathophysiology. AB - Intensive glycemic control may increase cardiovascular (CV) risk and mortality due to hypoglycemia. The pathophysiology of glucose counter-regulation in patients with type 1 or type 2 diabetes for over 15 years is characterized by impairment of the defense mechanisms against hypoglycemia. Hypoglycemia causes pronounced physiological and pathophysiological effects on the CV system as consequences of autonomic system activation and counter regulatory hormones release. These effects provoke a series of hemodynamic changes that include an increase in heart rate and peripheral systolic blood pressure, a decrease in central blood pressure, reduced peripheral arterial resistance, and increased myocardial contractility and cardiac output. Cardiac electrophysiological changes including flattening or inversion of T waves, QT prolongation, and ST segment depression were observed in both insulin-induced and spontaneous hypoglycemia. Sympathoadrenal activation is the main cause of these changes through mechanisms that involve, but are not limited to, catecholamine-mediated hypokalemia. Hypoglycemia is also involved in platelet activation. There is growing concern about the long-term effects of hypoglycemia, especially as related to inflammation and atherogenesis. PMID- 26685182 TI - Rebalance Without the Balance: A Research Note on the Availability of Community Based Services in Areas Where Nursing Homes Have Closed. AB - Policies to "rebalance" funding away from nursing homes and toward home and community-based services (HCBS) have encouraged national trends of nursing home closure and an expansion of the HCBS industry. These changes are unfolding without a clear understanding of what services are available at the local level. The purpose of this study was: (1) to describe the current distribution of community-based services (CBS) in areas where nursing homes have closed and (2) to examine differences in availability of CBS using local market and population characteristics as regressors in a multinomial logistic model. We collected data on and geocoded CBS facilities and then used ArcGIS to define a 5-mile radius around all nursing homes that closed between 2006 and 2010 and compared these local market areas. In rural areas, availability of CBS does not appear to compensate for nursing home closures. Policies encouraging HCBS may be outpacing availability of CBS, especially in rural areas. PMID- 26685183 TI - Comorbid bipolar disorder and obsessive-compulsive disorder: Which came first? PMID- 26685184 TI - Trends in the Management of Patients With Left Ventricular Assist Devices Presenting for Noncardiac Surgery: A 10-Year Institutional Experience. AB - In our institution, the vast majority of patients presenting for noncardiac surgery (NCS) while supported by a left ventricular assist device (LVAD) are now cared for by noncardiac-trained anesthesiologists as the result of a decade of educational intervention to effect this transition. This represents a significant departure from the published experiences of other institutions. With institutional review board approval, we queried the database of our anesthesia record keeping system (CompuRecord) to determine various aspects of the perioperative management of these patients from July 1, 2003, through June 30, 2013, during which time 271 NCS procedures were performed on adult patients supported by LVADs. Over the entire study period (2003-2013), anesthetic care was provided by a cardiac anesthesiologist 47% of the time and by a noncardiac anesthesiologist 53% of the time. However, by the time period 2012-2013, 88% of the NCS procedures were staffed by a noncardiac anesthesiologist. Despite the prevalence of continuous flow devices in this series, the use of invasive blood pressure monitoring decreased dramatically by the later years of the study. Vasoactive and inotropic medications were rarely required intraoperatively. No intraoperative cardiac arrests, thromboembolic complications, or device malfunctions occurred. Our conclusion is that NCS procedures on LVAD-supported patients can be safely managed by educated noncardiac anesthesiologists. PMID- 26685185 TI - Ectopic expression of TAPETUM DETERMINANT1 affects ovule development in Arabidopsis. AB - Plants have evolved to extensively employ leucine-rich repeat receptor-like kinases (LRR-RLKs), the largest family of RLKs, to control growth, development, and defense. In Arabidopsis thaliana, the EXCESS MICROSPOROCYTES1 (EMS1) LRR-RLK and its potential small protein ligand TAPETUM DETERMINANT1 (TPD1) are specifically required for anther cell differentiation; however, TPD1 and EMS1 orthologs also control megaspore mother cell proliferation in rice and maize ovules. Here, the molecular function of TPD1 was demonstrated during ovule development in Arabidopsis using a gain-of-function approach. In ovules, the EMS1 gene was primarily expressed in nucellus epidermis and chalaza, whereas the expression of TPD1 was weakly restricted to the distal end of integuments. Ectopic expression of TPD1 caused pleiotropic defects in ovule and seed development. RNA sequencing analysis showed that ectopic expression of TPD1 altered expression of auxin signaling genes and core cell-cycle genes during ovule development. Moreover, ectopic expression of TPD1 not only affected auxin response but also enhanced expression of cyclin genes CYCD3;3 and CYCA2;3 in ovules. Thus, these results provide insight into the molecular mechanism by which TPD1-EMS1 signaling controls plant development possibly via regulation of auxin signaling and cell-cycle genes. PMID- 26685187 TI - Flowering and trichome development share hormonal and transcription factor regulation. AB - Gibberellins (GAs) and cytokinins (CKs) are plant hormones that act either synergistically or antagonistically during the regulation of different developmental processes. In Arabidopsis thaliana, GAs and CKs overlap in the positive regulation of processes such as the transition from the vegetative to the reproductive phase and the development of epidermal adaxial trichomes. Despite the fact that both developmental processes originate in the rosette leaves, they occur separately in time and space. Here we review how, as genetic and molecular mechanisms are being unraveled, both processes might be closely related. Additionally, this shared genetic network is not only dependent on GA and CK hormone signaling but is also strictly controlled by specific clades of transcription factor families. Some key flowering genes also control other rosette leaf developmental processes such as adaxial trichome formation. Conversely, most of the trichome activator genes, which belong to the MYB, bHLH and C2H2 families, were found to positively control the floral transition. Furthermore, three MADS floral organ identity genes, which are able to convert leaves into floral structures, are also able to induce trichome proliferation in the flower. These data lead us to propose that the spatio-temporal regulation and integration of diverse signals control different developmental processes, such as floral induction and trichome formation, which are intimately connected through similar genetic pathways. PMID- 26685186 TI - Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants. AB - Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. PMID- 26685188 TI - The Hippo/STE20 homolog SIK1 interacts with MOB1 to regulate cell proliferation and cell expansion in Arabidopsis. AB - Multicellular organisms co-ordinate cell proliferation and cell expansion to maintain organ growth. In animals, the Hippo tumor suppressor pathway is a master regulator of organ size. Central to this pathway is a kinase cascade composed of Hippo and Warts, and their activating partners Salvador and Mob1/Mats. In plants, the Mob1/Mats homolog MOB1A has been characterized as a regulator of cell proliferation and sporogenesis. Nonetheless, no Hippo homologs have been identified. Here we show that the Arabidopsis serine/threonine kinase 1 (SIK1) is a Hippo homolog, and that it interacts with MOB1A to control organ size. SIK1 complements the function of yeast Ste20 in bud site selection and mitotic exit. The sik1 null mutant is dwarf with reduced cell numbers, endoreduplication, and cell expansion. A yeast two-hybrid screen identified Mob1/Mats homologs MOB1A and MOB1B as SIK1-interacting partners. The interaction between SIK1 and MOB1 was found to be mediated by an N-terminal domain of SIK1 and was further confirmed by bimolecular fluorescence complementation. Interestingly, sik1 mob1a is arrested at the seedling stage, and overexpression of neither SIK1 in mob1a nor MOB1A in sik1 can rescue the dwarf phenotypes, suggesting that SIK1 and MOB1 may be components of a larger protein complex. Our results pave the way for constructing a complete Hippo pathway that controls organ growth in higher plants. PMID- 26685189 TI - Non-targeted profiling of semi-polar metabolites in Arabidopsis root exudates uncovers a role for coumarin secretion and lignification during the local response to phosphate limitation. AB - Plants have evolved two major strategies to cope with phosphate (Pi) limitation. The systemic response, mainly comprising increased Pi uptake and metabolic adjustments for more efficient Pi use, and the local response, enabling plants to explore Pi-rich soil patches by reorganization of the root system architecture. Unlike previous reports, this study focused on root exudation controlled by the local response to Pi deficiency. To approach this, a hydroponic system separating the local and systemic responses was developed. Arabidopsis thaliana genotypes exhibiting distinct sensitivities to Pi deficiency could be clearly distinguished by their root exudate composition as determined by non-targeted reversed-phase ultraperformance liquid chromatography electrospray ionization quadrupole-time-of flight mass spectrometry metabolite profiling. Compared with wild-type plants or insensitive low phosphate root 1 and 2 (lpr1 lpr2) double mutant plants, the hypersensitive phosphate deficiency response 2 (pdr2) mutant exhibited a reduced number of differential features in root exudates after Pi starvation, suggesting the involvement of PDR2-encoded P5-type ATPase in root exudation. Identification and analysis of coumarins revealed common and antagonistic regulatory pathways between Pi and Fe deficiency-induced coumarin secretion. The accumulation of oligolignols in root exudates after Pi deficiency was inversely correlated with Pi starvation-induced lignification at the root tips. The strongest oligolignol accumulation in root exudates was observed for the insensitive lpr1 lpr2 double mutant, which was accompanied by the absence of Pi deficiency-induced lignin deposition, suggesting a role of LPR ferroxidases in lignin polymerization during Pi starvation. PMID- 26685191 TI - Further Validation of Triarchic Psychopathy Scales From the Multidimensional Personality Questionnaire: Setting the Stage for Large-Sample Etiological Studies. AB - Psychopathy as conceptualized by the triarchic model encompasses three distinct dispositional constructs: boldness, meanness, and disinhibition. The current study sought to further validate triarchic (Tri) construct scales composed of items from the Multidimensional Personality Questionnaire (MPQ) as a foundation for advancing research on the etiology of psychopathy using existing large-scale longitudinal studies. MPQ-Tri scales were examined in three samples: mixed-gender undergraduate students ( N = 346), male offenders from a residential substance abuse treatment facility ( N = 190), and incarcerated female offenders ( N = 216). Across these three samples, the MPQ-Tri scales demonstrated high internal consistency and clear convergent and discriminant associations with criterion measures of psychopathy and other psychopathology outcomes. Gender comparisons revealed relatively few differences in relationships with criterion measures. Findings are discussed in terms of their implications for further investigation of the causal bases of psychopathy and other forms of psychopathology utilizing data from large etiologically informative studies. PMID- 26685190 TI - Functional relationship between mTERF4 and GUN1 in retrograde signaling. AB - Plastid-to-nucleus retrograde signaling plays an important role in regulating the expression of photosynthesis-associated nuclear genes (PhANGs) in accordance with physiological demands on chloroplast biogenesis and function. Despite its fundamental importance, little is known about the molecular nature of the plastid gene expression (PGE)-dependent type of retrograde signaling. PGE is a multifaceted process, and several factors, including pentatricopeptide repeat (PPR) proteins, are involved in its regulation. The PPR protein GUN1 plays a central role in PGE-dependent retrograde signaling. In this study, we isolated a mutant exhibiting up-regulation of CHLOROPHYLL A/B-BINDING PROTEIN (CAB) under normal growth conditions (named coe1 for CAB overexpression 1). The coe1 mutant has a single-base mutation in the gene for mitochondrial transcription termination factor 4 (mTERF4)/BSM/RUG2, which plays a role in regulating the processing of certain plastid transcripts. Defects in GUN1 or mTERF4 de-repressed the expression of specific plastid mRNAs in the presence of lincomycin (LIN). In wild-type plants, treatment with LIN or spectinomycin (SPE) inhibited processing of plastid transcripts. Comparative analysis revealed that in gun1 and coe1/mterf4, but not in wild-type, gun4, or gun5 plants, the processing of plastid transcripts and expression levels of Lhcb1 mRNA were affected in opposite ways when plants were grown in the presence of LIN or SPE. In addition, the coe1 mutation affected the intracellular accumulation and distribution of GUN1, as well as its plastid signaling activity. Taken together, these results suggest that GUN1 and COE1 cooperate in PGE and retrograde signaling. PMID- 26685192 TI - Beyond Description in Interpersonal Construct Validation: Methodological Advances in the Circumplex Structural Summary Approach. AB - The interpersonal circumplex is a well-established structural model that organizes interpersonal functioning within the two-dimensional space marked by dominance and affiliation. The structural summary method (SSM) was developed to evaluate the interpersonal nature of other constructs and measures outside the interpersonal circumplex. To date, this method has been primarily descriptive, providing no way to draw inferences when comparing SSM parameters across constructs or groups. We describe a newly developed resampling-based method for deriving confidence intervals, which allows for SSM parameter comparisons. In a series of five studies, we evaluated the accuracy of the approach across a wide range of possible sample sizes and parameter values, and demonstrated its utility for posing theoretical questions on the interpersonal nature of relevant constructs (e.g., personality disorders) using real-world data. As a result, the SSM is strengthened for its intended purpose of construct evaluation and theory building. PMID- 26685194 TI - Changes in alcohol use in relation to sociodemographic factors in early midlife. AB - OBJECTIVE: To describe changes in alcohol use in relation to employment, education and relationship statuses in a general population sample in early midlife using prospective birth cohort data. MATERIALS AND METHODS: In the Northern Finland Birth Cohort 1966 (N=5621) alcohol use was studied in participants at two time points: ages 31 and 46. The total mean consumption was calculated and participants were classified into steady drinkers, increasers and reducers based on the change in consumption between the ages of 31 and 46. Multinomial regression analysis was conducted with changes in employment and relationship statuses. RESULTS: Daily alcohol consumption rose by 30% for men and 40% for women. Persons who were unemployed, single or had a low level of education consumed most. Of the alcohol users, 70% were classified as steady drinkers, 10% as reducers and 20% as increasers. For men, leaving a relationship (odds ratio, OR 1.5; 95% confidence interval, CI: 1.0-2.1) predicted increased alcohol use. The predictors of reducing consumption were entering a relationship for men (OR 1.9; 95% CI: 1.2-2.9) and women (OR 1.9; 95% CI: 1.1-3.1), and leaving a relationship (OR 2.6; 95% CI: 1.6-4.3) for women. CONCLUSIONS: Alcohol consumption among Finns of northern origin does not seem to decline with age. Alcohol usage is fairly stable in the majority of middle-aged people. A substantial proportion of alcohol users engage in either binge or heavy drinking. Gender differences in predictors exist-- changes in relationship status predict a reduction in alcohol usage in women, whereas in men, divorce predicts an increase in usage. PMID- 26685195 TI - Sickness absence and presence among employees in treatment for common mental disorders. AB - PURPOSE: Common mental disorders are a major cause of long-term sickness absence and a reason for disability benefits, although many people with these disorders remain employed. Therefore, it is important to prevent them from taking sick leave or relying on disability benefits. Consequently, we wished to identify the factors associated with sickness presence among patients undergoing treatment. METHOD: Participants were recruited from patients who met for their first session at a Return to Work clinic. A total of 251 patients completed a questionnaire that included questions on background information, mental health and functioning, and psychosocial work factors. Of these, 49% were fully working, 21.9% were partially working, and 29.1% were on full sickness absence. RESULTS: Fully working patients had fewer symptoms, functioned better, and experienced greater well-being than patients wholly on sick leave. They also experienced work as less demanding, were more appreciative, and had more employment security and autonomy. They reported symptoms, functioning, and well-being at the same level as the partially working group. However, their therapists reported that they functioned better and they themselves considered work demands somewhat less stressful. CONCLUSIONS THE RESULTS INDICATE THAT BOTH SYMPTOMS AND FUNCTIONAL CAPACITY, IN ADDITION TO WORK ENVIRONMENT, ARE PERCEIVED AS MORE FAVORABLE AMONG FULLY WORKING PATIENTS, COMPARED WITH THOSE COMPLETELY ON SICK LEAVE HOWEVER, BECAUSE OF THE CROSS-SECTIONAL DESIGN, WE NEED MORE STUDIES WITH PROSPECTIVE DESIGN TO EXAMINE WHETHER THESE RELATIONSHIPS ARE CAUSAL, AND TO EXAMINE WHEN SICKNESS PRESENCE IS BENEFICIAL FOR PATIENTS. PMID- 26685193 TI - Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. AB - We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to ameliorate TBI-induced cellular pathology. PMID- 26685196 TI - Moving on: How depressive symptoms, social support, and health behaviors predict residential mobility. AB - BACKGROUND: There are major health inequalities between residential areas. However, it remains unclear whether these inequalities are due to social causation or selective residential mobility, because little is known about the associations between health-related factors and selective residential mobility. This study examined how depressive symptoms, social support, and health behaviors are associated with subsequent residential mobility, as measured by frequency, distance, and direction of moves. METHODS: Participants were selected from the Young Finns prospective cohort study (N = 3017) with four study waves in 1992, 1997, 2001, and 2007. Complete residential mobility history was gathered for each participant from registry data. Residential mobility was assessed over three-year periods following each study wave. The direction of mobility was measured as changes in residential location's population density, health index, mortality index, and unemployment. Area characteristics were used as covariates together with the participants' age, sex, and education. RESULTS: Individuals reporting higher social support from friends were more likely to move (b = 0.20; 95% confidence interval (CI): 0.08, 0.37) and move more frequently (b = 0.08; 95% CI: 0.01, 0.14), whereas individuals reporting higher social support from their family members were less likely to move (b = -0.08; 95% CI: -0.14, -0.02). Better health behaviors were associated with longer moving distances (b = 0.14; 95% CI: 0.06, -0.23). None of the individual characteristics were associated with the direction of moves as measured by changes in municipality characteristics. CONCLUSIONS SOME OF THE HEALTH-RELATED CHARACTERISTICS ARE ASSOCIATED WITH RESIDENTIAL MOBILITY IN FINLAND HOWEVER, THESE INDIVIDUAL CHARACTERISTICS DO NOT SEEM TO PREDICT SYSTEMATIC SELECTIVE RESIDENTIAL MOBILITY ACROSS MUNICIPALITIES WITH DIFFERENT REGIONAL HEALTH PROFILES. PMID- 26685197 TI - Self-regulated compliance in preschoolers with autism spectrum disorder: The role of temperament and parental disciplinary style. AB - Regulatory difficulties are common in children with autism spectrum disorder. This study focused on an important aspect of self-regulation-the ability to willingly comply with frustrating demands of socialization agents, termed "self regulated compliance." We studied compliance to parental demands in 40 preschoolers with autism spectrum disorder and 40 matched typically developing preschoolers, during separate interactions with mother and father, while engaging in two paradigms: toy pick-up and delayed gratification, which tap the "do" and "don't" aspects of self-regulated socialization at this age. Parents' disciplinary style was micro-coded from the two paradigms and child temperament was parent reported. Compared to their typically developing peers, children with autism spectrum disorder showed more noncompliance and less self-regulated compliance to parental demands and prohibitions and greater temperamental difficulties across several domains. No group differences were found in parental disciplinary style. Child self-regulated compliance was associated with parental supportive disciplinary style and with child attention focusing. Findings highlight the importance of parental supportive presence in structuring the development of socialization in children with autism spectrum disorder. Implications for parent-child emotion regulation interventions are discussed. PMID- 26685198 TI - Stability and change in autism spectrum disorder diagnosis from age 3 to middle childhood in a high-risk sibling cohort. AB - Considerable evidence on autism spectrum disorder emergence comes from longitudinal high-risk samples (i.e. younger siblings of children with autism spectrum disorder). Diagnostic stability to age 3 is very good when diagnosed as early as 18-24 months, but sensitivity is weaker, and relatively little is known beyond toddlerhood. We examined stability and change in blinded, clinical best estimate diagnosis from age 3 to middle childhood (mean age = 9.5 years) in 67 high-risk siblings enrolled in infancy. Good agreement emerged for clinical best estimate diagnoses (89.6% overall; kappa = 0.76, p < 0.001, 95% confidence interval = 0.59-0.93). At age 3, 18 cases (26.9%) were classified with "autism spectrum disorder": 17 retained their autism spectrum disorder diagnosis (94.4%; 13 boys, 4 girls) and 1 no longer met autism spectrum disorder criteria at follow up. Among "non-autism spectrum disorder" cases at age 3, 43/49 remained non autism spectrum disorder at follow-up (87.8%; 22 boys, 21 girls) and 6/49 met lower autism symptomatology criteria ("Later-Diagnosed"; 3 boys, 3 girls). Later diagnosed cases had significantly lower autism spectrum disorder symptomatology and higher receptive language at age 3 and trends toward lower autism symptoms and higher cognitive abilities at follow-up. Emerging developmental concerns were noted in all later-diagnosed cases, by age 3 or 5. High-risk children need to be followed up into middle childhood, particularly when showing differences in autism-related domains. PMID- 26685199 TI - Clinical diagnosis of syphilis: a ten-year retrospective analysis in a South Australian urban sexual health clinic. AB - National notifications for infectious syphilis in Australia have increased in recent years. Outside of sexual health clinics, junior clinicians seldom encounter this disease in its infectious stage (primary, secondary and early latent). With such a variable clinical presentation, textbook teaching is no substitute for real-life experience. The importance of accurate classification and staging of disease is relevant to the risk of transmission and determines treatment duration. In this article, the authors review the clinical presentation of syphilis over ten years in an urban sexual health clinic with a focus on the clinical presentation and diagnosis of infectious syphilis, in particular secondary syphilis, compared with that outlined in the Australian National Notifiable Diseases Surveillance System guidelines. This retrospective review of all patients diagnosed with syphilis at an urban sexual health clinic showed that between 2005 and 2015, 226 cases of syphilis were diagnosed. Documentation of impression of clinical staging of disease was present in 46% of the cases. Seventeen of these cases were recorded as secondary syphilis. The criteria used by clinicians to diagnose the secondary syphilis cases were consistent with criteria defined by the Australian National Notifiable Diseases Surveillance System. All cases of secondary syphilis had at least one cutaneous manifestation of disease. The demographic of the cohort of syphilis cases was consistent with that recorded in the literature. This review showed that the clinician's diagnosis of secondary syphilis in this service is consistent with the National Notifiable Diseases Surveillance System guidelines. Continuing education of junior medical staff is important to facilitate diagnosis and improve documentation of clinical staging, minimise disease transmission and ensure appropriate treatment. PMID- 26685200 TI - Provision of HIV test results by telephone is both safe and efficient for men who have sex with men. AB - The aim of this study was to assess the impact of delivering HIV test results by telephone on HIV testing and subsequent risk behaviour of men, as well as saving on clinic consultation time. It was conducted at the Melbourne Sexual Health Centre, the main public sexual health clinic servicing Victoria, Australia. In 2013, a policy change was introduced so men could obtain their HIV test result via telephone. We compared the proportion of men testing for HIV and receiving results in the 24 months before (2011-2012) and the 24 months after (2013-2014) the policy change. There was a modest increase in the proportion of men having a HIV test of 3.2% ( p < 0.001) after the policy change. The provision of HIV results by telephone more than halved the number of men re-attending (74.4% vs. 33.1%) which freed up 516 hours of clinic time and had no adverse outcome on subsequent risk behaviour, nor changed the proportion of men who obtained their HIV results ( p = 0.058), or the period of time between testing and obtaining results for HIV-negative ( p = 0.007) and HIV-positive results ( p = 0.198). Telephone notification of HIV test results is a useful option given the potential beneficial effects shown. PMID- 26685201 TI - Special issue: the unstable wrist. PMID- 26685205 TI - IgG1 Allotypes Influence the Pharmacokinetics of Therapeutic Monoclonal Antibodies through FcRn Binding. AB - Because IgG1 allotypes might have different half-lives, their influence on infliximab (G1m17,1 allotype) pharmacokinetics was investigated in a group of spondyloarthritis patients. Infliximab was found to have a shorter half-life in patients homozygous for the G1m17,1 allotypes than in those carrying the G1m3 with no G1m1 (G1m3,-1) allotype. Because the neonatal FcR (FcRn) is involved in the pharmacokinetics of mAbs, the interaction of different IgG1 allotypes with FcRn was examined using cellular assays and surface plasmon resonance. G1m17,1 mAbs, such as infliximab and rituximab, were shown to bind more efficiently to FcRn and to be transcytosed better than the G1m3,-1 mAb cetuximab, which explains why infliximab is a better competitor for endogenous IgG1 in G1m3,-1 allotype bearing patients. A set of four allotype variants of adalimumab (G1m17,1; G1m17, 1; G1m3,1; and G1m3,-1) was also tested for its binding to FcRn, revealing that the G1m3,1 variant, not present in commercial mAbs, binds more efficiently to FcRn and is transcytosed better than the other three variants, all of which are found in therapeutic mAbs. PMID- 26685206 TI - IL-17A Is an Important Effector of the Immune Response of the Mammary Gland to Escherichia coli Infection. AB - The cytokine IL-17A has been shown to play critical roles in host defense against bacterial and fungal infections at different epithelial sites, but its role in the defense of the mammary gland (MG) has seldom been investigated, although infections of the MG constitute the main pathology afflicting dairy cows. In this study, we showed that IL-17A contributes to the defense of the MG against Escherichia coli infection by using a mouse mastitis model. After inoculation of the MG with a mastitis-causing E. coli strain, the bacterial load increased rapidly, triggering an intense influx of leukocytes into mammary tissue and increased concentrations of IL-6, IL-22, TNF-alpha, and IL-10. Neutrophils were the first cells that migrated intensely to the mammary tissue, in line with an early production of CXCL2. Depletion of neutrophils induced an increased mammary bacterial load. There was a significant increase of IL-17-containing CD4(+) alphabeta T lymphocyte numbers in infected glands. Depletion of IL-17A correlated with an increased bacterial colonization and IL-10 production. Intramammary infusion of IL-17A at the onset of infection was associated with markedly decreased bacterial numbers, decreased IL-10 production, and increased neutrophil recruitment. Depletion of CD25(+) regulatory T cells correlated with a decreased production of IL-10 and a reduced bacterial load. These results indicate that IL 17A is an important effector of MG immunity to E. coli and suggest that an early increased local production of IL-17A would improve the outcome of infection. These findings point to a new lead to the development of vaccines against mastitis. PMID- 26685207 TI - Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production. AB - With the stimulator of IFN genes (STING) C terminus being extensively studied, the role of the N-terminal domain (NTD) of STING remains an important subject of investigation. In this article, we identify novel mutations in NTD of Sting of the MOLF strain in response to HSV and Listeria monocytogenes both in vitro and in vivo. These mutations are responsible for low levels of IFN-beta caused by failure of MOLF STING to translocate from the endoplasmic reticulum. These data provide evidence that the NTD of STING affects DNA responses via control of trafficking. They also show that the genetic diversity of wild-derived mice resembles the diversity observed in humans. Several human alleles of STING confer attenuated IFN-I production similar to what we observe with the MOLF Sting allele, a crucial functional difference not apparent in classical inbred mice. Thus, understanding the functional significance of polymorphisms in MOLF STING can provide basic mechanistic insights relevant to humans. PMID- 26685210 TI - Using Brief Cognitive Restructuring and Cognitive Defusion Techniques to Cope With Negative Thoughts. AB - Negative thoughts, experienced by 80% to 99% of the non-clinical population, have been linked to the development of psychopathology. The current study aimed to compare a cognitive restructuring and cognitive defusion technique for coping with a personally relevant negative thought. Over a 5-day period, participants used either a restructuring, defusion, or control strategy to manage a negative thought. Pre- and post-intervention participants reported (a) believability of the thought, (b) discomfort associated with the thought, (c) negativity associated with the thought, and (d) willingness to experience the thought. Daily online questionnaires assessing the total frequency of negative thought intrusions and their level of willingness to experience the negative thought were also used. Also, 10 positive and negative self-statements were rated on the same scales, and self-report measures of mood and psychological flexibility were completed. Findings indicated that defusion lowered believability, increased comfort and willingness to have the target thought, and increased positive affect significantly more than the control and cognitive restructuring. Within groups, cognitive restructuring also made significant gains in target thought discomfort, negativity, and "willingness to have" in the same direction as defusion but the no-instruction control did not. Negative thought frequency was reduced in the defusion group, maintained in the restructuring group, and increased in the no instruction control group. Similar trends emerged from the secondary outcome measures, that is, the effects of the strategies on the positive and negative self-statements. The current findings support the efficacy of using defusion as a strategy for managing negative thoughts. PMID- 26685209 TI - Complex MHC Class I Gene Transcription Profiles and Their Functional Impact in Orangutans. AB - MHC haplotypes of humans and the African great ape species have one copy of the MHC-A, -B, and -C genes. In contrast, MHC haplotypes of orangutans, the Asian great ape species, exhibit variation in the number of gene copies. An in-depth analysis of the MHC class I gene repertoire in the two orangutan species, Pongo abelii and Pongo pygmaeus, is presented in this article. This analysis involved Sanger and next-generation sequencing methodologies, revealing diverse and complicated transcription profiles for orangutan MHC-A, -B, and -C. Thirty-five previously unreported MHC class I alleles are described. The data demonstrate that each orangutan MHC haplotype has one copy of the MHC-A gene, and that the MHC-B region has been subject to duplication, giving rise to at least three MHC-B genes. The MHC-B*03 and -B*08 lineages of alleles each account for a separate MHC B gene. All MHC-B*08 allotypes have the C1-epitope motif recognized by killer cell Ig-like receptor. At least one other MHC-B gene is present, pointing to MHC B alleles that are not B*03 or B*08. The MHC-C gene is present only on some haplotypes, and each MHC-C allotype has the C1-epitope. The transcription profiles demonstrate that MHC-A alleles are highly transcribed, whereas MHC-C alleles, when present, are transcribed at very low levels. The MHC-B alleles are transcribed to a variable extent and over a wide range. For those orangutan MHC class I allotypes that are detected by human monoclonal anti-HLA class I Abs, the level of cell-surface expression of proteins correlates with the level of transcription of the allele. PMID- 26685208 TI - The Transcription Factor ARID3a Is Important for In Vitro Differentiation of Human Hematopoietic Progenitors. AB - We recently reported that the transcription factor ARID3a is expressed in a subset of human hematopoietic progenitor stem cells in both healthy individuals and in patients with systemic lupus erythematosus. Numbers of ARID3a(+) lupus hematopoietic stem progenitor cells were associated with increased production of autoreactive Abs when those cells were introduced into humanized mouse models. Although ARID3a/Bright knockout mice died in utero, they exhibited decreased numbers of hematopoietic stem cells and erythrocytes, indicating that ARID3a is functionally important for hematopoiesis in mice. To explore the requirement for ARID3a for normal human hematopoiesis, hematopoietic stem cell progenitors from human cord blood were subjected to both inhibition and overexpression of ARID3a in vitro. Inhibition of ARID3a resulted in decreased B lineage cell production accompanied by increases in cells with myeloid lineage markers. Overexpression of ARID3a inhibited both myeloid and erythroid differentiation. Additionally, inhibition of ARID3a in hematopoietic stem cells resulted in altered expression of transcription factors associated with hematopoietic lineage decisions. These results suggest that appropriate regulation of ARID3a is critical for normal development of both myeloid and B lineage pathways. PMID- 26685213 TI - Posttraumatic Stress Symptoms, Burn-Out, and Compassion Satisfaction Among Body Handlers: The Mediating Role of Sense of Coherence and Spirituality at Workplace. AB - This study assessed posttraumatic stress symptoms (PTSS), burn-out (BO), and compassion satisfaction (CS) among Israeli body handlers. We aimed to explore differences between two groups of Orthodox Jewish male volunteers: the "ZAKA" body handlers (ZAs: n = 102), and a comparison group of charity workers (CWs: n = 101). Furthermore, we assessed the contribution of two potential resilience buffers-sense of coherence (SOC) and spirituality at the workplace (SAW)-to PTSS, BO, and CS among these volunteers via self-report measures. Surprisingly, results show that ZAs reported significantly lower levels of PTSS and BO as compared with CWs. ZAs also reported significantly higher levels of CS as compared with CWs. Importantly, SOC mediated the link between groups and PTSS and BO. Both SOC and SAW mediated the link between groups and CS. These findings suggest that "ZAKA" body handlers demonstrate substantial resilience following repeated exposure to death and atrocities. To reduce work-related psychological distress and improve CS, SOC and SAW should be taken into account in the process of recruitment and training of body handlers. PMID- 26685211 TI - HIV-Associated Toxic Epidermal Necrolysis at San Francisco General Hospital. AB - OBJECTIVES: We sought to characterize recent cases of toxic epidermal necrolysis (TEN) in HIV-infected patients at San Francisco General Hospital (SFGH), a large HIV referral center. METHODS: This was a retrospective analysis of HIV-infected patients diagnosed with TEN from January 2001 to May 2014 at SFGH. RESULTS: Ten cases of TEN were identified, 50% of which occurred in HIV-infected individuals. Among the HIV-associated cases, causative agents were trimethoprim sulfamethoxazole (TMP-SMX; n = 2), atovaquone, clindamycin, and fluconazole. No antiretroviral agents were implicated. CONCLUSION: Although limited by small sample size, our experience is reflective of the well-recognized increased incidence of TEN in HIV-positive patients and suggests that antimicrobial agents, particularly TMP-SMX, are the most common causative agents in this population. As 3 of the 5 HIV-associated TEN cases were caused by potentially inappropriate or unnecessary use of antibiotics, our experience highlights the importance of judicious use of systemic medications in populations susceptible to severe adverse drug reactions. PMID- 26685214 TI - Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts. AB - Despite advances in treatment approaches for head and neck squamous cell carcinoma (HNSCC), survival rates have remained stagnant due to the paucity of preclinical models that accurately reflect the human tumor. Patient-derived xenografts (PDX) are an emerging model system where patient tumors are implanted directly into mice. Increased understanding of the application and limitations of PDXs will facilitate their rational use. Studies to date have not reported protein profiles of PDXs. Therefore, we developed a large cohort of HNSCC PDXs and found that tumor take rate was not influenced by the clinical, pathologic, or processing features. Protein expression profiles, from a subset of the PDXs, were characterized by reverse-phase protein array and the data was compared with The Cancer Genome Atlas HNSCC data. Cluster analysis revealed that HNSCC PDXs were more similar to primary HNSCC than to any other tumor type. Interestingly, while a significant fraction of proteins were expressed similarly in both primary HNSCC and PDXs, a subset of proteins/phosphoproteins were expressed at higher (or lower) levels in PDXs compared with primary HNSCC. These findings indicate that the proteome is generally conserved in PDXs, but mechanisms for both positive and negative model selection and/or differences in the stromal components exist. IMPLICATIONS: Proteomic characterization of HNSCC PDXs demonstrates potential drivers for model selection and provides a framework for improved utilization of this expanding model system. PMID- 26685218 TI - Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development. AB - Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this site on the genome decreased drought tolerance, but increased glucosinolate concentration. PMID- 26685215 TI - Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention. AB - Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anticancer effects are still being elucidated. We hypothesized that aspirin's chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The downregulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. First, inclusion of salicylic acid in naive cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. IMPLICATIONS: Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID- 26685219 TI - Inflammation and Hemostatic Activation may Contribute to Postsurgical Thrombosis in Patients With Bladder Cancer. AB - The alterations of the inflammatory and thrombotic components in patients with cancer are not clearly understood. The purpose of this study was to profile markers of inflammation and thrombotic activation specifically in the patients with bladder cancer undergoing radical cystectomy. For this study, 134 samples were collected from patients undergoing radical cystectomy. Antiphospholipid antibodies (immunoglobulin G subtype), microparticles, and antiglycosaminoglycan antibodies were measured with a commercially available enzyme-linked immunosorbent assay kits. These biomarkers were compared in patients with bladder cancer and normal individuals (n = 20). Patients had an average value of 6.7 +/- 11.9 ng/mL (median: 2.8, confidence interval: 4.69-8.75, andPvalue: .0038) of antiphospholipid antibodies versus normal individuals 1.96 +/- 0.9 ng/mL (median: 1.8 and confidence interval: 1.5-2.35). Microparticles level in patients was 8.31 +/- 6.14 ng/mL, (median: 6.1, confidence interval: 7.26-9.37, andPvalue: <.0001) versus normal individuals 3.57 +/- 2.34 ng/mL (median: 2.85 and confidence interval: 2.476-4.664). The antiglycosaminoglycan antibodies in patients had an average value of 0.22 +/- 0.1 optical density (OD; median: 0.2, confidence interval: 0.21-0.24, andPvalue: .0213) compared to normal individuals 0.25 +/- 0.08 OD (median: 0.25 and confidence interval: 0.22-0.23). The correlation of antiglycosaminoglycan antibodies with antiphospholipid antibodies showed Spearmanrvalue = .2364 (95% confidence interval: 0.05-0.4 andPvalue .009). The correlation of antiglycosaminoglycan antibodies versus microparticles showed Spearmanr= -.195 (95% confidence interval: 0.37-0.01 andPvalue .0321). These data suggest that patients with bladder cancer have subclinical activation of thrombotic and inflammatory processes that may be further exacerbated by surgical procedures and lead to venous thromboembolism-related complications. PMID- 26685221 TI - Preliminary Upper Estimate of Peak Currents in Transcranial Magnetic Stimulation at Distant Locations From a TMS Coil. AB - GOALS: Transcranial magnetic stimulation (TMS) is increasingly used as a diagnostic and therapeutic tool for numerous neuropsychiatric disorders. The use of TMS might cause whole-body exposure to undesired induced currents in patients and TMS operators. The aim of this study is to test and justify a simple analytical model known previously, which may be helpful as an upper estimate of eddy current density at a particular distant observation point for any body composition and any coil setup. METHODS: We compare the analytical solution with comprehensive adaptive mesh refinement-based FEM simulations of a detailed full body human model, two coil types, five coil positions, about 100 000 observation points, and two distinct pulse rise times; thus, providing a representative number of different datasets for comparison, while also using other numerical data. RESULTS: Our simulations reveal that, after a certain modification, the analytical model provides an upper estimate for the eddy current density at any location within the body. In particular, it overestimates the peak eddy currents at distant locations from a TMS coil by a factor of 10 on average. CONCLUSION: The simple analytical model tested in this study may be valuable as a rapid method to safely estimate levels of TMS currents at different locations within a human body. SIGNIFICANCE: At present, safe limits of general exposure to TMS electric and magnetic fields are an open subject, including fetal exposure for pregnant women. PMID- 26685222 TI - A Novel Algorithm for Remote Photoplethysmography: Spatial Subspace Rotation. AB - In this paper, we propose a conceptually novel algorithm, namely "Spatial Subspace Rotation" (2SR), that improves the robustness of remote photoplethysmography. Based on the assumption of 1) spatially redundant pixel sensors of a camera, and 2) a well-defined skin mask, our core idea is to estimate a spatial subspace of skin-pixels and measure its temporal rotation for pulse extraction, which does not require skin-tone or pulse-related priors in contrast to existing algorithms. The proposed algorithm is thoroughly assessed on a benchmark dataset containing 54 videos, which includes challenges of various skin-tones, body-motions in complex illuminance conditions, and pulse-rate recovery after exercise. The experimental results show that given a well-defined skin mask, 2SR outperforms the popular ICA-based approach and two state-of-the art algorithms (CHROM and PBV). When comparing the pulse frequency spectrum, 2SR improves on average the SNR of ICA by 2.22 dB, CHROM by 1.56 dB, and PBV by 1.95 dB. When comparing the instant pulse-rate, 2SR improves on average the Pearson correlation and precision of ICA by 47% and 65%, CHROM by 22% and 23%, and PBV by 21% and 39%. ANOVA confirms the significant improvement of 2SR in peak-to-peak accuracy. The proposed 2SR algorithm is very simple to use and extend, i.e., the implementation only requires a few lines MATLAB code. PMID- 26685220 TI - Assessing the Electromagnetic Fields Generated By a Radiofrequency MRI Body Coil at 64 MHz: Defeaturing Versus Accuracy. AB - GOAL: This study aims at a systematic assessment of five computational models of a birdcage coil for magnetic resonance imaging (MRI) with respect to accuracy and computational cost. METHODS: The models were implemented using the same geometrical model and numerical algorithm, but different driving methods (i.e., coil "defeaturing"). The defeatured models were labeled as: specific (S2), generic (G32, G16), and hybrid (H16, [Formula: see text]). The accuracy of the models was evaluated using the "symmetric mean absolute percentage error" ("SMAPE"), by comparison with measurements in terms of frequency response, as well as electric ( ||->E||) and magnetic ( || ->B ||) field magnitude. RESULTS: All the models computed the || ->B || within 35% of the measurements, only the S2, G32, and H16 were able to accurately model the ||->E|| inside the phantom with a maximum SMAPE of 16%. Outside the phantom, only the S2 showed a SMAPE lower than 11%. CONCLUSIONS: Results showed that assessing the accuracy of || ->B || based only on comparison along the central longitudinal line of the coil can be misleading. Generic or hybrid coils - when properly modeling the currents along the rings/rungs - were sufficient to accurately reproduce the fields inside a phantom while a specific model was needed to accurately model ||->E|| in the space between coil and phantom. SIGNIFICANCE: Computational modeling of birdcage body coils is extensively used in the evaluation of radiofrequency-induced heating during MRI. Experimental validation of numerical models is needed to determine if a model is an accurate representation of a physical coil. PMID- 26685223 TI - A Space-Time-Frequency Dictionary for Sparse Cortical Source Localization. AB - OBJECTIVE: Cortical source imaging aims at identifying activated cortical areas on the surface of the cortex from the raw electroencephalogram (EEG) data. This problem is ill posed, the number of channels being very low compared to the number of possible source positions. METHODS: In some realistic physiological situations, the active areas are sparse in space and of short time durations, and the amount of spatio-temporal data to carry the inversion is then limited. In this study, we propose an original data driven space-time-frequency (STF) dictionary which takes into account simultaneously both spatial and time frequency sparseness while preserving smoothness in the time frequency (i.e., nonstationary smooth time courses in sparse locations). Based on these assumptions, we take benefit of the matching pursuit (MP) framework for selecting the most relevant atoms in this highly redundant dictionary. RESULTS: We apply two recent MP algorithms, single best replacement (SBR) and source deflated matching pursuit, and we compare the results using a spatial dictionary and the proposed STF dictionary to demonstrate the improvements of our multidimensional approach. We also provide comparison using well-established inversion methods, FOCUSS and RAP-MUSIC, analyzing performances under different degrees of nonstationarity and signal to noise ratio. CONCLUSION: Our STF dictionary combined with the SBR approach provides robust performances on realistic simulations. From a computational point of view, the algorithm is embedded in the wavelet domain, ensuring high efficiency in term of computation time. SIGNIFICANCE: The proposed approach ensures fast and accurate sparse cortical localizations on highly nonstationary and noisy data. PMID- 26685224 TI - Nonlinear Difference Imaging Approach to Three-Dimensional Electrical Impedance Tomography in the Presence of Geometric Modeling Errors. AB - OBJECTIVE: To evaluate the recently proposed nonlinear difference imaging approach to electrical impedance tomography (EIT) in realistic 3-D geometries. METHODS: In this paper, the feasibility of nonlinear difference approach-based EIT is tested using simulation studies in 3-D geometries of thorax and larynx, and with an experimental study of a thorax-shaped water tank. All test cases exhibit severe modeling errors due to uncertainty in the boundary shape of the body. RESULTS: In all test cases, the conductivity change reconstructed with nonlinear difference imaging outperforms the conventional reconstructions qualitatively and quantitatively. CONCLUSION: The results demonstrate that the nonlinear difference reconstructions tolerate geometrical modeling errors at least to the same extent as the conventional linear approach and produce quantitatively more accurate information on the conductivity change. SIGNIFICANCE: Physiological processes that produce changes in the electrical conductivity of the body can be monitored with difference imaging based on EIT. The wide popularity of linearized difference imaging in EIT is mainly based on its good tolerance for the ubiquitous modeling errors, which are predominantly caused by inexact knowledge of the body geometry. However, the linearized difference imaging produces only qualitative information on the conductivity change, and the feasibility of the estimates also depends on the selection of the linearization point which ideally should be equal to the conductivity of the initial state. Based on the findings of this paper, these problems can be avoided by nonlinear difference imaging, and potentially the approach can enable quantitative imaging of conductivity change in medical applications. PMID- 26685225 TI - A Patch-Based Approach for the Segmentation of Pathologies: Application to Glioma Labelling. AB - In this paper, we describe a novel and generic approach to address fully automatic segmentation of brain tumors by using multi-atlas patch-based voting techniques. In addition to avoiding the local search window assumption, the conventional patch-based framework is enhanced through several simple procedures: an improvement of the training dataset in terms of both label purity and intensity statistics, augmented features to implicitly guide the nearest-neighbor search, multi-scale patches, invariance to cube isometries, stratification of the votes with respect to cases and labels. A probabilistic model automatically delineates regions of interest enclosing high-probability tumor volumes, which allows the algorithm to achieve highly competitive running time despite minimal processing power and resources. This method was evaluated on Multimodal Brain Tumor Image Segmentation challenge datasets. State-of-the-art results are achieved, with a limited learning stage thus restricting the risk of overfit. Moreover, segmentation smoothness does not involve any post-processing. PMID- 26685226 TI - Deformable MR Prostate Segmentation via Deep Feature Learning and Sparse Patch Matching. AB - Automatic and reliable segmentation of the prostate is an important but difficult task for various clinical applications such as prostate cancer radiotherapy. The main challenges for accurate MR prostate localization lie in two aspects: (1) inhomogeneous and inconsistent appearance around prostate boundary, and (2) the large shape variation across different patients. To tackle these two problems, we propose a new deformable MR prostate segmentation method by unifying deep feature learning with the sparse patch matching. First, instead of directly using handcrafted features, we propose to learn the latent feature representation from prostate MR images by the stacked sparse auto-encoder (SSAE). Since the deep learning algorithm learns the feature hierarchy from the data, the learned features are often more concise and effective than the handcrafted features in describing the underlying data. To improve the discriminability of learned features, we further refine the feature representation in a supervised fashion. Second, based on the learned features, a sparse patch matching method is proposed to infer a prostate likelihood map by transferring the prostate labels from multiple atlases to the new prostate MR image. Finally, a deformable segmentation is used to integrate a sparse shape model with the prostate likelihood map for achieving the final segmentation. The proposed method has been extensively evaluated on the dataset that contains 66 T2-wighted prostate MR images. Experimental results show that the deep-learned features are more effective than the handcrafted features in guiding MR prostate segmentation. Moreover, our method shows superior performance than other state-of-the-art segmentation methods. PMID- 26685227 TI - Relaxed Linearized Algorithms for Faster X-Ray CT Image Reconstruction. AB - Statistical image reconstruction (SIR) methods are studied extensively for X-ray computed tomography (CT) due to the potential of acquiring CT scans with reduced X-ray dose while maintaining image quality. However, the longer reconstruction time of SIR methods hinders their use in X-ray CT in practice. To accelerate statistical methods, many optimization techniques have been investigated. Over relaxation is a common technique to speed up convergence of iterative algorithms. For instance, using a relaxation parameter that is close to two in alternating direction method of multipliers (ADMM) has been shown to speed up convergence significantly. This paper proposes a relaxed linearized augmented Lagrangian (AL) method that shows theoretical faster convergence rate with over-relaxation and applies the proposed relaxed linearized AL method to X-ray CT image reconstruction problems. Experimental results with both simulated and real CT scan data show that the proposed relaxed algorithm (with ordered-subsets [OS] acceleration) is about twice as fast as the existing unrelaxed fast algorithms, with negligible computation and memory overhead. PMID- 26685228 TI - Dynamic MRI Using SmooThness Regularization on Manifolds (SToRM). AB - We introduce a novel algorithm to recover real time dynamic MR images from highly under-sampled k- t space measurements. The proposed scheme models the images in the dynamic dataset as points on a smooth, low dimensional manifold in high dimensional space. We propose to exploit the non-linear and non-local redundancies in the dataset by posing its recovery as a manifold smoothness regularized optimization problem. A navigator acquisition scheme is used to determine the structure of the manifold, or equivalently the associated graph Laplacian matrix. The estimated Laplacian matrix is used to recover the dataset from undersampled measurements. The utility of the proposed scheme is demonstrated by comparisons with state of the art methods in multi-slice real time cardiac and speech imaging applications. PMID- 26685229 TI - Efficient Small Blob Detection Based on Local Convexity, Intensity and Shape Information. AB - The identification of small structures (blobs) from medical images to quantify clinically relevant features, such as size and shape, is important in many medical applications. One particular application explored here is the automated detection of kidney glomeruli after targeted contrast enhancement and magnetic resonance imaging. We propose a computationally efficient algorithm, termed the Hessian-based Difference of Gaussians (HDoG), to segment small blobs (e.g., glomeruli from kidney) from 3D medical images based on local convexity, intensity and shape information. The image is first smoothed and pre-segmented into small blob candidate regions based on local convexity. Two novel 3D regional features (regional blobness and regional flatness) are then extracted from the candidate regions. Together with regional intensity, the three features are used in an unsupervised learning algorithm for auto post-pruning. HDoG is first validated in a 2D form and compared with other three blob detectors from literature, which are generally for 2D images only. To test the detectability of blobs from 3D images, 240 sets of simulated images are rendered for scenarios mimicking the renal nephron distribution observed in contrast-enhanced, 3D MRI. The results show a satisfactory performance of HDoG in detecting large numbers of small blobs. Two sets of real kidney 3D MR images (6 rats, 3 human) are then used to validate the applicability of HDoG for glomeruli detection. By comparing MRI to stereological measurements, we verify that HDoG is a robust and efficient unsupervised technique for 3D blobs segmentation. PMID- 26685230 TI - Excitation of Single-Mode Lamb Waves at High-Frequency-Thickness Products. AB - Guided wave inspection is used extensively in petrochemical plants to check for defects such as corrosion. Long-range low-frequency inspection can be used to detect relatively large defects, while higher frequency inspection provides improved sensitivity to small defects, but the presence of multiple dispersive modes makes it difficult to implement. This paper investigates the possibility of exciting a single-mode Lamb wave with low dispersion at a frequency thickness of around 20 MHz-mm. It is shown by finite element (FE) analysis backed up by experiments that a signal dominated by the A1 mode can be generated, even in a region where many modes have similar phase velocities. The A1 mode has relatively little motion at the plate surface which means that only a small reflection is generated at features such as T-joints; this is verified numerically. It is also expected that it will be relatively unaffected by surface roughness or attenuative coatings. These features are very similar to those of the higher order mode cluster (HOMC) reported by other authors, and it is shown that the A1 mode shape is very similar to the deflected shape reported in HOMC. PMID- 26685232 TI - MATLAB/Simulink Pulse-Echo Ultrasound System Simulator Based on Experimentally Validated Models. AB - A flexible clinical ultrasound system must operate with different transducers, which have characteristic impulse responses and widely varying impedances. The impulse response determines the shape of the high-voltage pulse that is transmitted and the specifications of the front-end electronics that receive the echo; the impedance determines the specification of the matching network through which the transducer is connected. System-level optimization of these subsystems requires accurate modeling of pulse-echo (two-way) response, which in turn demands a unified simulation of the ultrasonics and electronics. In this paper, this is realized by combining MATLAB/Simulink models of the high-voltage transmitter, the transmission interface, the acoustic subsystem which includes wave propagation and reflection, the receiving interface, and the front-end receiver. To demonstrate the effectiveness of our simulator, the models are experimentally validated by comparing the simulation results with the measured data from a commercial ultrasound system. This simulator could be used to quickly provide system-level feedback for an optimized tuning of electronic design parameters. PMID- 26685231 TI - Left-Atrial Segmentation From 3-D Ultrasound Using B-Spline Explicit Active Surfaces With Scale Uncoupling. AB - Segmentation of the left atrium (LA) of the heart allows quantification of LA volume dynamics which can give insight into cardiac function. However, very little attention has been given to LA segmentation from three-dimensional (3-D) ultrasound (US), most efforts being focused on the segmentation of the left ventricle (LV). The B-spline explicit active surfaces (BEAS) framework has been shown to be a very robust and efficient methodology to perform LV segmentation. In this study, we propose an extension of the BEAS framework, introducing B splines with uncoupled scaling. This formulation improves the shape support for less regular and more variable structures, by giving independent control over smoothness and number of control points. Semiautomatic segmentation of the LA endocardium using this framework was tested in a setup requiring little user input, on 20 volumetric sequences of echocardiographic data from healthy subjects. The segmentation results were evaluated against manual reference delineations of the LA. Relevant LA morphological and functional parameters were derived from the segmented surfaces, in order to assess the performance of the proposed method on its clinical usage. The results showed that the modified BEAS framework is capable of accurate semiautomatic LA segmentation in 3-D transthoracic US, providing reliable quantification of the LA morphology and function. PMID- 26685233 TI - Autonomous Rubidium Clock Weak Frequency Jump Detector for Onboard Navigation Satellite System. AB - Frequency jumps are common in rubidium frequency sources. They affect the estimation of user position in navigational satellite systems. These jumps must be detected and corrected immediately as they have direct impact on the navigation system integrity. A novel weak frequency jump detector is proposed based on a Kalman filter with a multi-interval approach. This detector can be applied for both "sudden" and "slow" frequency transitions. In this detection method, noises of clock data are reduced by Kalman filtering, for accurate estimation of jump size with less latency. Analysis on in-orbit rubidium atomic frequency standard (RAFS) phase telemetry data shows that the detector can be used for fast detection and correction of weak frequency jumps. Furthermore, performance comparison of different existing frequency jump detection techniques with the proposed detector is discussed. A multialgorithm-based strategy is proposed depending on the jump size and latency for onboard navigation satellites having RAFS as the primary frequency source. PMID- 26685234 TI - Contrast Enhancement by Nonlinear Diffusion Filtering. AB - To enhance the visual quality of an image that is degraded by uneven light, an effective method is to estimate the illumination component and compress it. Some previous methods have either defects of halo artifacts or contrast loss in the enhanced image due to incorrect estimation. In this paper, we discuss this problem and propose a novel method to estimate the illumination. The illumination is obtained by iteratively solving a nonlinear diffusion equation. During the diffusion process, surround suppression is embedded in the conductance function to specially enhance the diffusive strength in textural areas of the image. The proposed estimation method has the following two merits: 1) the boundary areas are preserved in the illumination, and thus halo artifacts are prevented and 2) the textural details are preserved in the reflectance to not suffer from illumination compression, which contributes to the contrast enhancement in the result. Experimental results show that the proposed algorithm achieves excellent performance in artifact removal and local contrast enhancement. PMID- 26685235 TI - Robust Texture Image Representation by Scale Selective Local Binary Patterns. AB - Local binary pattern (LBP) has successfully been used in computer vision and pattern recognition applications, such as texture recognition. It could effectively address grayscale and rotation variation. However, it failed to get desirable performance for texture classification with scale transformation. In this paper, a new method based on dominant LBP in scale space is proposed to address scale variation for texture classification. First, a scale space of a texture image is derived by a Gaussian filter. Then, a histogram of pre-learned dominant LBPs is built for each image in the scale space. Finally, for each pattern, the maximal frequency among different scales is considered as the scale invariant feature. Extensive experiments on five public texture databases (University of Illinois at Urbana-Champaign, Columbia Utrecht Database, Kungliga Tekniska Hogskolan-Textures under varying Illumination, Pose and Scale, University of Maryland, and Amsterdam Library of Textures) validate the efficiency of the proposed feature extraction scheme. Coupled with the nearest subspace classifier, the proposed method could yield competitive results, which are 99.36%, 99.51%, 99.39%, 99.46%, and 99.71% for UIUC, CUReT, KTH-TIPS, UMD, and ALOT, respectively. Meanwhile, the proposed method inherits simple and efficient merits of LBP, for example, it could extract scale-robust feature for a 200*200 image within 0.24 s, which is applicable for many real-time applications. PMID- 26685236 TI - Surveillance Video Synopsis via Scaling Down Objects. AB - Video synopsis is an effective technique to provide a compact representation of the original video by removing spatiotemporal redundancies and by preserving the essential activities. Most current approaches for video synopsis will cause collisions among objects, especially when the video is condensed much. In this paper, we present an approach for video synopsis to reduce the collisions. Our approach first shifts active objects along the time axis to compact the original video. Then, the sizes of the objects are reduced when collisions occur. Meanwhile, the geometric centroids of the objects will be kept unchanged to preserve the location information. Our contributions are threefold. First, an approach is proposed to decrease collisions in the synopsis video through reducing the sizes of the objects. Second, an optimization framework is developed to indicate the optimal time position and the appropriate reduction coefficient for each object. Finally, some metrics are proposed, and several experiments are carried out to evaluate the proposed approach. The experiments have demonstrated that the synopsis video produced by our approach has much fewer collisions while the compression ratio is high. PMID- 26685237 TI - Design of Steerable Wavelets to Detect Multifold Junctions. AB - We propose a framework for the detection of junctions in images. Although the detection of edges and key points is a well examined and described area, the multiscale detection of junction centers, especially for odd orders, poses a challenge in pattern analysis. The goal of this paper is to build optimal junction detectors based on 2D steerable wavelets that are polar-separable in the Fourier domain. The approaches we develop are general and can be used for the detection of arbitrary symmetric and asymmetric junctions. The backbone of our construction is a multiscale pyramid with a radial wavelet function where the directional components are represented by circular harmonics and encoded in a shaping matrix. We are able to detect M -fold junctions in different scales and orientations. We provide experimental results on both simulated and real data to demonstrate the effectiveness of the algorithm. PMID- 26685238 TI - Depth Estimation Using a Sliding Camera. AB - Image-based 3D reconstruction technology is widely used in different fields. The conventional algorithms are mainly based on stereo matching between two or more fixed cameras, and high accuracy can only be achieved using a large camera array, which is very expensive and inconvenient in many applications. Another popular choice is utilizing structure-from-motion methods for arbitrarily placed camera(s). However, due to too many degrees of freedom, its computational cost is heavy and its accuracy is rather limited. In this paper, we propose a novel depth estimation algorithm using a sliding camera system. By analyzing the geometric properties of the camera system, we design a camera pose initialization algorithm that can work satisfyingly with only a small number of feature points and is robust to noise. For pixels corresponding to different depths, an adaptive iterative algorithm is proposed to choose optimal frames for stereo matching, which can take advantage of continuously pose-changing imaging and save the time consumption amazingly too. The proposed algorithm can also be easily extended to handle less constrained situations (such as using a camera mounted on a moving robot or vehicle). Experimental results on both synthetic and real-world data have illustrated the effectiveness of the proposed algorithm. PMID- 26685239 TI - Identification of Transform Coding Chains. AB - Transform coding is routinely used for lossy compression of discrete sources with memory. The input signal is divided into N-dimensional vectors, which are transformed by means of a linear mapping. Then, transform coefficients are quantized and entropy coded. In this paper, we consider the problem of identifying the transform matrix as well as the quantization step sizes. First, we study the case in which the only available information is a set of P transform decoded vectors. We formulate the problem in terms of finding the lattice with the largest determinant that contains all observed vectors. We propose an algorithm that is able to find the optimal solution and we formally study its convergence properties. Three potential realms of application are considered as example scenarios for the proposed theory: 1) parameter retrieval in the presence of a chain of two transform coders; 2) image tampering identification; and 3) parameter estimation for predictive coders. We show that, despite their differences, all three scenarios can be tackled by applying the same fundamental methodology. Experiments on both the synthetic data and the real images validate the proposed approach. PMID- 26685240 TI - Compressive Sequential Learning for Action Similarity Labeling. AB - Human action recognition in videos has been extensively studied in recent years due to its wide range of applications. Instead of classifying video sequences into a number of action categories, in this paper, we focus on a particular problem of action similarity labeling (ASLAN), which aims at verifying whether a pair of videos contain the same type of action or not. To address this challenge, a novel approach called compressive sequential learning (CSL) is proposed by leveraging the compressive sensing theory and sequential learning. We first project data points to a low-dimensional space by effectively exploring an important property in compressive sensing: the restricted isometry property. In particular, a very sparse measurement matrix is adopted to reduce the dimensionality efficiently. We then learn an ensemble classifier for measuring similarities between pairwise videos by iteratively minimizing its empirical risk with the AdaBoost strategy on the training set. Unlike conventional AdaBoost, the weak learner for each iteration is not explicitly defined and its parameters are learned through greedy optimization. Furthermore, an alternative of CSL named compressive sequential encoding is developed as an encoding technique and followed by a linear classifier to address the similarity-labeling problem. Our method has been systematically evaluated on four action data sets: ASLAN, KTH, HMDB51, and Hollywood2, and the results show the effectiveness and superiority of our method for ASLAN. PMID- 26685241 TI - Sparse Hashing Tracking. AB - In this paper, we propose a novel tracking framework based on a sparse and discriminative hashing method. Different from the previous work, we treat object tracking as an approximate nearest neighbor searching process in a binary space. Using the hash functions, the target templates and the candidates can be projected into the Hamming space, facilitating the distance calculation and tracking efficiency. First, we integrate both the inter-class and intra-class information to train multiple hash functions for better classification, while most classifiers in previous tracking methods usually neglect the inter-class correlation, which may cause the inaccuracy. Then, we introduce sparsity into the hash coefficient vectors for dynamic feature selection, which is crucial to select the discriminative and stable features to adapt to visual variations during the tracking process. Extensive experiments on various challenging sequences show that the proposed algorithm performs favorably against the state of-the-art methods. PMID- 26685242 TI - Variational Phase Imaging Using the Transport-of-Intensity Equation. AB - We introduce a variational phase retrieval algorithm for the imaging of transparent objects. Our formalism is based on the transport-of-intensity equation (TIE), which relates the phase of an optical field to the variation of its intensity along the direction of propagation. TIE practically requires one to record a set of defocus images to measure the variation of intensity. We first investigate the effect of the defocus distance on the retrieved phase map. Based on our analysis, we propose a weighted phase reconstruction algorithm yielding a phase map that minimizes a convex functional. The method is nonlinear and combines different ranges of spatial frequencies - depending on the defocus value of the measurements - in a regularized fashion. The minimization task is solved iteratively via the alternating-direction method of multipliers. Our simulations outperform commonly used linear and nonlinear TIE solvers. We also illustrate and validate our method on real microscopy data of HeLa cells. PMID- 26685243 TI - Nonparametric Detection of Nonlinearly Mixed Pixels and Endmember Estimation in Hyperspectral Images. AB - Mixing phenomena in hyperspectral images depend on a variety of factors, such as the resolution of observation devices, the properties of materials, and how these materials interact with incident light in the scene. Different parametric and nonparametric models have been considered to address hyperspectral unmixing problems. The simplest one is the linear mixing model. Nevertheless, it has been recognized that the mixing phenomena can also be nonlinear. The corresponding nonlinear analysis techniques are necessarily more challenging and complex than those employed for linear unmixing. Within this context, it makes sense to detect the nonlinearly mixed pixels in an image prior to its analysis, and then employ the simplest possible unmixing technique to analyze each pixel. In this paper, we propose a technique for detecting nonlinearly mixed pixels. The detection approach is based on the comparison of the reconstruction errors using both a Gaussian process regression model and a linear regression model. The two errors are combined into a detection statistics for which a probability density function can be reasonably approximated. We also propose an iterative endmember extraction algorithm to be employed in combination with the detection algorithm. The proposed detect-then-unmix strategy, which consists of extracting endmembers, detecting nonlinearly mixed pixels and unmixing, is tested with synthetic and real images. PMID- 26685244 TI - Coupled Learning for Facial Deblur. AB - Blur in facial images significantly impedes the efficiency of recognition approaches. However, most existing blind deconvolution methods cannot generate satisfactory results due to their dependence on strong edges, which are sufficient in natural images but not in facial images. In this paper, we represent point spread functions (PSFs) by the linear combination of a set of pre defined orthogonal PSFs, and similarly, an estimated intrinsic (EI) sharp face image is represented by the linear combination of a set of pre-defined orthogonal face images. In doing so, PSF and EI estimation is simplified to discovering two sets of linear combination coefficients, which are simultaneously found by our proposed coupled learning algorithm. To make our method robust to different types of blurry face images, we generate several candidate PSFs and EIs for a test image, and then, a non-blind deconvolution method is adopted to generate more EIs by those candidate PSFs. Finally, we deploy a blind image quality assessment metric to automatically select the optimal EI. Thorough experiments on the facial recognition technology database, extended Yale face database B, CMU pose, illumination, and expression (PIE) database, and face recognition grand challenge database version 2.0 demonstrate that the proposed approach effectively restores intrinsic sharp face images and, consequently, improves the performance of face recognition. PMID- 26685246 TI - Multinomial Latent Logistic Regression for Image Understanding. AB - In this paper, we present multinomial latent logistic regression (MLLR), a new learning paradigm that introduces latent variables to logistic regression. By inheriting the advantages of logistic regression, MLLR is efficiently optimized using the second-order derivatives and provides effective probabilistic analysis on output predictions. MLLR is particularly effective in weakly supervised settings where the latent variable has an exponential number of possible values. The effectiveness of MLLR is demonstrated on four different image understanding applications, including a new challenging architectural style classification task. Furthermore, we show that MLLR can be generalized to general structured output prediction, and in doing so, we provide a thorough investigation of the connections and differences between MLLR and existing related algorithms, including latent structural SVMs and hidden conditional random fields. PMID- 26685247 TI - Fused One-vs-All Features With Semantic Alignments for Fine-Grained Visual Categorization. AB - Fine-grained visual categorization is an emerging research area and has been attracting growing attention recently. Due to the large inter-class similarity and intra-class variance, it is extremely challenging to recognize objects in fine-grained domains. A traditional spatial pyramid matching model could obtain desirable results for the basic-level category classification by weak alignment, but may easily fail in fine-grained domains, since the discriminative features are extremely localized. This paper proposes a new framework for fine-grained visual categorization. First, an efficient part localization method incorporates semantic prior into geometric alignment. It detects the less deformable parts, such as the head of birds with a template-based model, and localizes other highly deformable parts with simple geometric alignment. Second, we learn one-vs-all features, which are simple and transplantable. The learned mid-level features are dimension friendly and more robust to outlier instances. Furthermore, in view that some subcategories are too similar to tell them apart easily, we fuse the subcategories iteratively according to their similarities, and learn fused one-vs all features. Experimental results show the superior performance of our algorithms over the existing methods. PMID- 26685245 TI - The Radon Cumulative Distribution Transform and Its Application to Image Classification. AB - Invertible image representation methods (transforms) are routinely employed as low-level image processing operations based on which feature extraction and recognition algorithms are developed. Most transforms in current use (e.g., Fourier, wavelet, and so on) are linear transforms and, by themselves, are unable to substantially simplify the representation of image classes for classification. Here, we describe a nonlinear, invertible, low-level image processing transform based on combining the well-known Radon transform for image data, and the 1D cumulative distribution transform proposed earlier. We describe a few of the properties of this new transform, and with both theoretical and experimental results show that it can often render certain problems linearly separable in a transform space. PMID- 26685248 TI - Focus Profile Modeling. AB - A focus profile depicts the image sharpness (or focus value) as the lens sweeps along the optical axis of a camera. Accurate modeling of the focus profile is important to many imaging tasks. In this paper, we present an approach to focus profile modeling that makes the search of in-focus lens position a mathematically tractable problem, and hereby improves the efficiency and accuracy of image acquisition. The proposed approach entails a transformation that converts the representation of a focus profile to quadratic form. An important feature of the approach is that no prior knowledge of the focus measurement technique is required. Experimental results are provided to demonstrate the effectiveness of the approach. PMID- 26685249 TI - Modality-Driven Classification and Visualization of Ensemble Variance. AB - Advances in computational power now enable domain scientists to address conceptual and parametric uncertainty by running simulations multiple times in order to sufficiently sample the uncertain input space. While this approach helps address conceptual and parametric uncertainties, the ensemble datasets produced by this technique present a special challenge to visualization researchers as the ensemble dataset records a distribution of possible values for each location in the domain. Contemporary visualization approaches that rely solely on summary statistics (e.g., mean and variance) cannot convey the detailed information encoded in ensemble distributions that are paramount to ensemble analysis; summary statistics provide no information about modality classification and modality persistence. To address this problem, we propose a novel technique that classifies high-variance locations based on the modality of the distribution of ensemble predictions. Additionally, we develop a set of confidence metrics to inform the end-user of the quality of fit between the distribution at a given location and its assigned class. Finally, for the special application of evaluating the stability of bimodal regions, we develop local and regional metrics. PMID- 26685250 TI - Just Noticeable Distortion Profile for Flat-Shaded 3D Mesh Surfaces. AB - It is common that a 3D mesh undergoes some lossy operations (e.g., compression, watermarking and transmission through noisy channels), which can introduce geometric distortions as a change in vertex position. In most cases the end users of 3D meshes are human beings; therefore, it is important to evaluate the visibility of introduced vertex displacement. In this paper we present a model for computing a Just Noticeable Distortion (JND) profile for flat-shaded 3D meshes. The proposed model is based on an experimental study of the properties of the human visual system while observing a flat-shaded 3D mesh surface, in particular the contrast sensitivity function and contrast masking. We first define appropriate local perceptual properties on 3D meshes. We then detail the results of a series of psychophysical experiments where we have measured the threshold needed for a human observer to detect the change in vertex position. These results allow us to compute the JND profile for flat-shaded 3D meshes. The proposed JND model has been evaluated via a subjective experiment, and applied to guide 3D mesh simplification as well as to determine the optimal vertex coordinates quantization level for a 3D model. PMID- 26685251 TI - 3D Navigation on Impossible Figures via Dynamically Reconfigurable Maze. AB - Previous research on impossible figures focuses extensively on single view modeling and rendering. Existing computer games that employ impossible figures as navigation maze for gaming either use a fixed third-person view with axonometric projection to retain the figure's impossibility perception, or simply break the figure's impossibility upon view changes. In this paper, we present a new approach towards 3D gaming with impossible figures, delivering for the first time navigation in 3D mazes constructed from impossible figures. Such result cannot be achieved by previous research work in modeling impossible figures. To deliver seamless gaming navigation and interaction, we propose i) a set of guiding principles for bringing out subtle perceptions and ii) a novel computational approach to construct 3D structures from impossible figure images and then to dynamically construct the impossible-figure maze subjected to user's view. In the end, we demonstrate and discuss our method with a variety of generic maze types. PMID- 26685252 TI - Motion Effects Synthesis for 4D Films. AB - 4D film is an immersive entertainment system that presents various physical effects with a film in order to enhance viewers' experiences. Despite the recent emergence of 4D theaters, production of 4D effects relies on manual authoring. In this paper, we present algorithms that synthesize three classes of motion effects from the audiovisual content of a film. The first class of motion effects is those responding to fast camera motion to enhance the immersiveness of point-of view shots, delivering fast and dynamic vestibular feedback. The second class moves viewers as closely as possible to the trajectory of slowly moving camera. Such motion provides an illusional effect of observing the scene from a distance while moving slowly within the scene. For these two classes, our algorithms compute the relative camera motion and then map it to a motion command to the 4D chair using appropriate motion mapping algorithms. The last class is for special effects, such as explosions, and our algorithm uses sound for the synthesis of impulses and vibrations. We assessed the subjective quality of our algorithms by user experiments, and results indicated that our algorithms can provide compelling motion effects. PMID- 26685253 TI - Visual Trends Analysis in Time-Varying Ensembles. AB - Visualization and analysis techniques play a key role in the discovery of relevant features in ensemble data. Trends, in the form of persisting commonalities or differences in time-varying ensemble datasets, constitute one of the most expressive feature types in ensemble analysis. We develop a flow-graph representation as the core of a system designed for the visual analysis of trends in time-varying ensembles. In our interactive analysis framework, this graph is linked to a representation of ensemble parameter-space and the ensemble itself. This facilitates a detailed examination of trends and their correlations to properties of input-space. We demonstrate the utility of the proposed trends analysis framework in several benchmark data sets, highlighting its capability to support goal-driven design of time-varying simulations. PMID- 26685254 TI - Visualizing Dynamic Hierarchies in Graph Sequences. AB - Graphs are used to model relations between objects, where these objects can be grouped hierarchically based on their connectivity. In many applications, the relations change over time and so does the hierarchical group structure. We developed a visualization technique that supports the analysis of the topology and the hierarchical group structure of a dynamic graph and the tracking of changes over time. Each graph of a sequence is visualized by an adjacency matrix, where the hierarchical group structure is encoded within the matrix using indentation and nested contours, complemented by icicle plots attached to the matrices. The density within and between subgroups of the hierarchy is represented within the matrices using a gray scale. To visualize changes, transitions and dissimilarities between the hierarchically structured graphs are shown using a flow metaphor and color coding. The design of our visualization technique allows us to show more than one hierarchical group structure of the same graph by stacking the sequences, where hierarchy comparison is supported not only within but also between sequences. To improve the readability, we minimize the number of crossing curves within and between sequences based on a sorting algorithm that sweeps through the sequences of hierarchies. PMID- 26685255 TI - Learning Predictive Movement Models From Fabric-Mounted Wearable Sensors. AB - The measurement and analysis of human movement for applications in clinical diagnostics or rehabilitation is often performed in a laboratory setting using static motion capture devices. A growing interest in analyzing movement in everyday environments (such as the home) has prompted the development of "wearable sensors", with the most current wearable sensors being those embedded into clothing. A major issue however with the use of these fabric-embedded sensors is the undesired effect of fabric motion artefacts corrupting movement signals. In this paper, a nonparametric method is presented for learning body movements, viewing the undesired motion as stochastic perturbations to the sensed motion, and using orthogonal regression techniques to form predictive models of the wearer's motion that eliminate these errors in the learning process. Experiments in this paper show that standard nonparametric learning techniques underperform in this fabric motion context and that improved prediction accuracy can be made by using orthogonal regression techniques. Modelling this motion artefact problem as a stochastic learning problem shows an average 77% decrease in prediction error in a body pose task using fabric-embedded sensors, compared to a kinematic model. PMID- 26685256 TI - The Effects of Stimulation Strategy on Joint Movement Elicited by Intraspinal Microstimulation. AB - The goal of this study was to characterize the effects of stimulation parameters and multielectrode stimulation on selectivity, range of motion, recruitment characteristics, and fatigue during intraspinal microstimulation (ISMS). A custom made multielectrode array was implanted into the activation pool of the rat dorsiflexor muscle where the stimulation produced the highest movement range on the ankle joint and the least effect on the other joints. The results show that the selectivity could be significantly enhanced using multielectrode stimulation strategy. Moreover, the fatigue was significantly reduced using multielectrode synchronous stimulation with respect to single-electrode stimulation. For a given charge, stimulation with higher current amplitude and shorter pulse duration produced greater range of motion than that with lower amplitude and longer pulse duration. However, the stimulation with shorter duration caused greater fatigue than that with longer. In addition, there was a significant difference in time constant of spinal response obtained with different pulse amplitudes during pulse width (PW) modulation. The time constant decreased with increasing pulse amplitude. However, there was no significant effect of pulse duration on time constant during pulse amplitude (PA) modulation. The results suggest that the motor neurons (MNs) within the spinal cord can be recruited according to size principle by appropriate selection of stimulation parameters. Based on these results an efficient stimulation strategy can be designed for control of movement performance (i.e., speed of movement, fatigue, range of motion, and selectivity) during ISMS. PMID- 26685257 TI - Real-Time Adaptive EEG Source Separation Using Online Recursive Independent Component Analysis. AB - Independent component analysis (ICA) has been widely applied to electroencephalographic (EEG) biosignal processing and brain-computer interfaces. The practical use of ICA, however, is limited by its computational complexity, data requirements for convergence, and assumption of data stationarity, especially for high-density data. Here we study and validate an optimized online recursive ICA algorithm (ORICA) with online recursive least squares (RLS) whitening for blind source separation of high-density EEG data, which offers instantaneous incremental convergence upon presentation of new data. Empirical results of this study demonstrate the algorithm's: 1) suitability for accurate and efficient source identification in high-density (64-channel) realistically simulated EEG data; 2) capability to detect and adapt to nonstationarity in 64-ch simulated EEG data; and 3) utility for rapidly extracting principal brain and artifact sources in real 61-channel EEG data recorded by a dry and wearable EEG system in a cognitive experiment. ORICA was implemented as functions in BCILAB and EEGLAB and was integrated in an open-source Real-time EEG Source-mapping Toolbox (REST), supporting applications in ICA-based online artifact rejection, feature extraction for real-time biosignal monitoring in clinical environments, and adaptable classifications in brain-computer interfaces. PMID- 26685258 TI - Home-Based Risk of Falling Assessment Test Using a Closed-Loop Balance Model. AB - The aim of this study is to improve and facilitate the methods used to assess risk of falling at home among older people through the computation of a risk of falling in real time in daily activities. In order to increase a real time computation of the risk of falling, a closed-loop balance model is proposed and compared with One-Leg Standing Test (OLST). This balance model allows studying the postural response of a person having an unpredictable perturbation. Twenty nine volunteers participated in this study for evaluating the effectiveness of the proposed system which includes seventeen elder participants: ten healthy elderly ( 68.4 +/-5.5 years), seven Parkinson's disease (PD) subjects ( 66.28 +/ 8.9 years), and twelve healthy young adults ( 28.27 +/-3.74 years). Our work suggests that there is a relationship between OLST score and the risk of falling based on center of pressure measurement with four low cost force sensors located inside an instrumented insole, which could be predicted using our suggested closed-loop balance model. For long term monitoring at home, this system could be included in a medical electronic record and could be useful as a diagnostic aid tool. PMID- 26685259 TI - Low-Complexity Noncoherent Signal Detection for Nanoscale Molecular Communications. AB - Nanoscale molecular communication is a viable way of exchanging information between nanomachines. In this investigation, a low-complexity and noncoherent signal detection technique is proposed to mitigate the inter-symbol-interference (ISI) and additive noise. In contrast to existing coherent detection methods of high complexity, the proposed noncoherent signal detector is more practical when the channel conditions are hard to acquire accurately or hidden from the receiver. The proposed scheme employs the molecular concentration difference to detect the ISI corrupted signals and we demonstrate that it can suppress the ISI effectively. The difference in molecular concentration is a stable characteristic, irrespective of the diffusion channel conditions. In terms of complexity, by excluding matrix operations or likelihood calculations, the new detection scheme is particularly suitable for nanoscale molecular communication systems with a small energy budget or limited computation resource. PMID- 26685260 TI - Intra-Body Optical Channel Modeling for In Vivo Wireless Nanosensor Networks. AB - In vivo wireless nanosensor networks (iWNSNs) consist of nanosized communicating devices, which can operate inside the human body in real time. iWNSNs are at the basis of transformative healthcare techniques, ranging from intra-body health monitoring systems to drug-delivery applications. Plasmonic nanoantennas are expected to enable the communication among nanosensors in the near infrared and optical transmission window. This result motivates the analysis of the phenomena affecting the propagation of such electromagnetic (EM) signals inside the human body. In this paper, a channel model for intra-body optical communication among nanosensors is developed. The total path loss is computed by taking into account the absorption from different types of molecules and the scattering by different types of cells. In particular, first, the impact of a single cell on the propagation of an optical wave is analytically obtained, by modeling a cell as a multi-layer sphere with complex permittivity. Then, the impact of having a large number of cells with different properties arranged in layered tissues is analyzed. The analytical channel model is validated by means of electromagnetic simulations and extensive numerical results are provided to understand the behavior of the intra-body optical wireless channel. The result shows that, at optical frequencies, the scattering loss introduced by cells is much larger than the absorption loss from the medium. This result motivates the utilization of the lower frequencies of the near-infrared window for communication in iWNSNs. PMID- 26685261 TI - Gold Nanoparticles Impair Foot-and-Mouth Disease Virus Replication. AB - In this study, we evaluated the antiviral activity of gold nanoparticles (AuNPs) against the foot-and-mouth disease virus (FMDV), that causes a contagious disease in cloven-hoofed animals. The anti-FMDV activity of AuNPs was assessed using plaque reduction assay. MTT assay was used for quantitatively measuring the cytopathic effect caused by the viral infection. The 50% cytotoxicity concentration of nanoparticles was measured and found to be 10.4 MUg/ml. The virus yield reduction assay showed that AuNP have an approximately 4-fold virus titer reduction compared with controls. Plaque reduction assay showed that at non cytotoxic concentrations, AuNPs do not show extracellular virucidal activity and inhibition of FMDV growth at the early stages of infection including attachment and penetration. Time-of-addition experiments revealed that AuNPs inhibited post entry stages of viral replication concomitant with the onset of intracellular viral RNA synthesis; however, the mechanism of AuNPs against FMDV was unclear. PMID- 26685262 TI - On Frictional Forces between the Finger and a Textured Surface during Active Touch. AB - We investigated forces felt by a bare finger in sliding contact with a textured surface, and how they depend on properties of the surface and contact interaction. Prior research has shed light on haptic texture perception. Nevertheless, how texture-produced forces depend on the properties of a touched object or the way that it is touched is less clear. To address this, we designed an apparatus to accurately measure contact forces between a sliding finger and a textured surface. We fabricated textured surfaces, and measured spatial variations in forces produced as subjects explored the surfaces with a bare finger. We analyzed variations in these force signals, and their dependence on object geometry and contact parameters. We observed a number of phenomena, including transient stick-slip behavior, nonlinearities, phase variations, and large force fluctuations, in the form of aperiodic signal components that proved difficult to model for fine surfaces. Moreover, metrics such as total harmonic distortion and normalized variance decreased as the spatial scale of the stimuli increased. The results of this study suggest that surface geometry and contact parameters are insufficient to account for force production during such interactions. Moreover, the results shed light on perceptual challenges solved by the haptic system during active touch sensing of surface texture. PMID- 26685263 TI - Systematic Movements in Haptic Search: Spirals, Zigzags, and Parallel Sweeps. AB - Movement strategies were investigated in a one-handed haptic search task in which blindfolded-sighted participants used either one or five fingers to find a landmark on an unstructured tactile map. Search theory predicts that systematic strategies, such as spirals, zigzags, and parallel sweeps, should be more prevalent when the searcher's detection radius is small (one finger) and less common when the detection radius is large (five fingers). As predicted, systematic strategies were more common in one-finger than five-finger search. Participants were able to exploit the larger detection radius during five-finger searches to detect targets with any of their fingers, and in one-finger search used more systematic strategies. For the most part, participants' fingers moved together during five-finger search, expanding and moving quickly when looking for search targets/distractors, and contracting and moving slowly when examining search targets/distractors. There was no evidence of fingers being used as spatial anchors or other independent finger movements in five-finger search. While targets could be found with any fingers, examination was primarily accomplished using the index and middle fingers. Overall, these results indicate that untrained sighted participants will use optimal systematic strategies during haptic search, and this behavior is appropriately modulated by detection radius. PMID- 26685264 TI - K-MEAP: Multiple Exemplars Affinity Propagation With Specified $K$ Clusters. AB - Recently, an attractive clustering approach named multiexemplar affinity propagation (MEAP) has been proposed as an extension to the single exemplar-based AP. MEAP is able to automatically identify multiple exemplars for each cluster associated with a superexemplar. However, if the cluster number is a prior knowledge and can be specified by the user, MEAP is unable to make use of such knowledge directly in its learning process. Instead, it has to rely on rerunning the process as many times as it takes by tuning parameters until it generates the desired number of clusters. The process of MEAP rerunning may be very time consuming. In this paper, we propose a new clustering algorithm called Multiple Exemplars Affinity Propagation with Specified K Clusters which is able to generate specified K clusters directly while retaining the advantages of MEAP. Two kinds of new additional messages are introduced in K-MEAP in order to control the number of clusters in the process of message passing. Detailed problem formulation, derived messages, and in-depth analysis of the proposed K-MEAP are provided. Experimental studies on 11 real-world data sets with different kinds of applications demonstrate that K-MEAP not only generates K clusters directly and efficiently without tuning parameters but also outperforms related approaches in terms of clustering accuracy. PMID- 26685265 TI - 3-D Laser-Based Multiclass and Multiview Object Detection in Cluttered Indoor Scenes. AB - This paper investigates the problem of multiclass and multiview 3-D object detection for service robots operating in a cluttered indoor environment. A novel 3-D object detection system using laser point clouds is proposed to deal with cluttered indoor scenes with a fewer and imbalanced training data. Raw 3-D point clouds are first transformed to 2-D bearing angle images to reduce the computational cost, and then jointly trained multiple object detectors are deployed to perform the multiclass and multiview 3-D object detection. The reclassification technique is utilized on each detected low confidence bounding box in the system to reduce false alarms in the detection. The RUS-SMOTEboost algorithm is used to train a group of independent binary classifiers with imbalanced training data. Dense histograms of oriented gradients and local binary pattern features are combined as a feature set for the reclassification task. Based on the dalian university of technology (DUT)-3-D data set taken from various office and household environments, experimental results show the validity and good performance of the proposed method. PMID- 26685266 TI - A ParaBoost Method to Image Quality Assessment. AB - An ensemble method for full-reference image quality assessment (IQA) based on the parallel boosting (ParaBoost) idea is proposed in this paper. We first extract features from existing image quality metrics and train them to form basic image quality scorers (BIQSs). Then, we select additional features to address specific distortion types and train them to construct auxiliary image quality scorers (AIQSs). Both BIQSs and AIQSs are trained on small image subsets of certain distortion types and, as a result, they are weak performers with respect to a wide variety of distortions. Finally, we adopt the ParaBoost framework, which is a statistical scorer selection scheme for support vector regression (SVR), to fuse the scores of BIQSs and AIQSs to evaluate the images containing a wide range of distortion types. This ParaBoost methodology can be easily extended to images of new distortion types. Extensive experiments are conducted to demonstrate the superior performance of the ParaBoost method, which outperforms existing IQA methods by a significant margin. Specifically, the Spearman rank order correlation coefficients (SROCCs) of the ParaBoost method with respect to the LIVE, CSIQ, TID2008, and TID2013 image quality databases are 0.98, 0.97, 0.98, and 0.96, respectively. PMID- 26685267 TI - A Cooperative Learning-Based Clustering Approach to Lip Segmentation Without Knowing Segment Number. AB - It is usually hard to predetermine the true number of segments in lip segmentation. This paper, therefore, presents a clustering-based approach to lip segmentation without knowing the true segment number. The objective function in the proposed approach is a variant of the partition entropy (PE) and features that the coincident cluster centroids in pattern space can be equivalently substituted by one centroid with the function value unchanged. It is shown that the minimum of the proposed objective function can be reached provided that: 1) the number of positions occupied by cluster centroids in pattern space is equal to the true number of clusters and 2) these positions are coincident with the optimal cluster centroids obtained under PE criterion. In implementation, we first randomly initialize the clusters provided that the number of clusters is greater than or equal to the ground truth. Then, an iterative algorithm is utilized to minimize the proposed objective function. For each iterative step, not only is the winner, i.e., the centroid with the maximum membership degree, updated to adapt to the corresponding input data, but also the other centroids are adjusted with a specific cooperation strength, so that they are each close to the winner. Subsequently, the initial overpartition will be gradually faded out with the redundant centroids superposed over the convergence of the algorithm. Based upon the proposed algorithm, we present a lip segmentation scheme. Empirical studies have shown its efficacy in comparison with the existing methods. PMID- 26685268 TI - Adaptive Output Neural Network Control for a Class of Stochastic Nonlinear Systems With Dead-Zone Nonlinearities. AB - This paper investigates the problem of adaptive output neural network (NN) control for a class of stochastic nonaffine and nonlinear systems with actuator dead-zone inputs. First, based on the intermediate value theorem, a novel design scheme that converts the nonaffine system into the corresponding affine system is developed. In particular, the priori knowledge of the bound of the derivative of the nonaffine and nonlinear functions is removed; then, by employing NNs to approximate the appropriate nonlinear functions, the corresponding adaptive NN tracking controller with the adjustable parameter updated laws is designed through a backstepping technique. Furthermore, it is shown that all the closed loop signals are bounded in probability, and the system output tracking error can converge to a small neighborhood in the sense of a mean quartic value. Finally, experimental simulations are provided to demonstrate the efficiency of the proposed adaptive NN tracking control method. PMID- 26685269 TI - Stability Analysis of Neural Networks With Two Delay Components Based on Dynamic Delay Interval Method. AB - In this paper, a dynamic delay interval (DDI) method is proposed to deal with the stability problem of neural networks with two delay components. This method extends the fixed interval of a time-varying delay to a dynamic one, which relaxes the restriction on upper and lower bounds of the delay intervals. Combining the reciprocally convex combination technique and Wirtinger integral inequality, the DDI method leads to some much less conservative delay-dependent stability criteria based on a linear matrix inequality for neural networks with two delay components. Furthermore, the criteria for the system with a single time varying delay are provided. Some examples are given to illustrate the effectiveness of the obtained results. PMID- 26685270 TI - Density-Dependent Quantized Least Squares Support Vector Machine for Large Data Sets. AB - Based on the knowledge that input data distribution is important for learning, a data density-dependent quantization scheme (DQS) is proposed for sparse input data representation. The usefulness of the representation scheme is demonstrated by using it as a data preprocessing unit attached to the well-known least squares support vector machine (LS-SVM) for application on big data sets. Essentially, the proposed DQS adopts a single shrinkage threshold to obtain a simple quantization scheme, which adapts its outputs to input data density. With this quantization scheme, a large data set is quantized to a small subset where considerable sample size reduction is generally obtained. In particular, the sample size reduction can save significant computational cost when using the quantized subset for feature approximation via the Nystrom method. Based on the quantized subset, the approximated features are incorporated into LS-SVM to develop a data density-dependent quantized LS-SVM (DQLS-SVM), where an analytic solution is obtained in the primal solution space. The developed DQLS-SVM is evaluated on synthetic and benchmark data with particular emphasis on large data sets. Extensive experimental results show that the learning machine incorporating DQS attains not only high computational efficiency but also good generalization performance. PMID- 26685271 TI - Multimodal Degradation Prognostics Based on Switching Kalman Filter Ensemble. AB - For accurate prognostics, users have to determine the current health of the system and predict future degradation pattern of the system. An increasingly popular approach toward tackling prognostic problems involves the use of switching models to represent various degradation phases, which the system undergoes. Such approaches have the advantage of determining the exact degradation phase of the system and being able to handle nonlinear degradation models through piecewise linear approximation. However, limitations of such existing methods include, limited applicability due to the discretization of predicted remaining useful life, insufficient robustness due to the use of single models and others. This paper circumvents these limitations by proposing a hybrid of ensemble methods with switching methods. The proposed method first implements a switching Kalman filter (SKF) to classify between various linear degradation phases, then predict the future propagation of fault dimension using appropriate Kalman filters for each phase. This proposed method achieves both continuous and discrete prediction values representing the remaining life and degradation phase of the system, respectively. The proposed framework is shown via a case study on benchmark simulated aeroengine data sets. The evaluation of the proposed framework shows that the proposed method achieves better accuracy and robustness against noise compared with other methods reported in the literature. The results also indicate the effectiveness of the SKF in detecting the switching point between various degradation modes. PMID- 26685272 TI - Learning the Conformal Transformation Kernel for Image Recognition. AB - In this paper, we present a multiclass data classifier, denoted by optimal conformal transformation kernel (OCTK), based on learning a specific kernel model, the CTK, and utilize it in two types of image recognition tasks, namely, face recognition and object categorization. We show that the learned CTK can lead to a desirable spatial geometry change in mapping data from the input space to the feature space, so that the local spatial geometry of the heterogeneous regions is magnified to favor a more refined distinguishing, while that of the homogeneous regions is compressed to neglect or suppress the intraclass variations. This nature of the learned CTK is of great benefit in image recognition, since in image recognition we always have to face a challenge that the images to be classified are with a large intraclass diversity and interclass similarity. Experiments on face recognition and object categorization show that the proposed OCTK classifier achieves the best or second best recognition result compared with that of the state-of-the-art classifiers, no matter what kind of feature or feature representation is used. In computational efficiency, the OCTK classifier can perform significantly faster than the linear support vector machine classifier (linear LIBSVM) can. PMID- 26685273 TI - Discriminative Feature Extraction by a Neural Implementation of Canonical Correlation Analysis. AB - The canonical correlation analysis (CCA) aims at measuring linear relationships between two sets of variables (views) that can be used for feature extraction in classification problems with multiview data. However, the correlated features extracted by the CCA may not be class discriminative, since CCA does not utilize the class labels in its traditional formulation. Although there is a method called discriminative CCA (DCCA) that aims to increase the discriminative ability of CCA inspired from the linear discriminant analysis (LDA), it has been shown that the extracted features with this method are identical to those by the LDA with respect to an orthogonal transformation. Therefore, DCCA is simply equivalent to applying single-view (regular) LDA to each one of the views separately. Besides, DCCA and the other similar DCCA approaches have generalization problems due to the sample covariance matrices used in their computation, which are sensitive to outliers and noisy samples. In this paper, we propose a method, called discriminative alternating regression (D-AR), to explore correlated and also discriminative features. D-AR utilizes two (alternating) multilayer perceptrons, each with a linear hidden layer, learning to predict both the class labels and the outputs of each other. We show that the features found by D-AR on training sets significantly accomplish higher classification accuracies on test sets of facial expression recognition, object recognition, and image retrieval experimental data sets. PMID- 26685274 TI - Monitoring Nonlinear and Non-Gaussian Processes Using Gaussian Mixture Model Based Weighted Kernel Independent Component Analysis. AB - A kernel independent component analysis (KICA) is widely regarded as an effective approach for nonlinear and non-Gaussian process monitoring. However, the KICA based monitoring methods treat every KIC equally and cannot highlight the useful KICs associated with fault information. Consequently, fault information may not be explored effectively, which may result in degraded fault detection performance. To overcome this problem, we propose a new nonlinear and non Gaussian process monitoring method using Gaussian mixture model (GMM)-based weighted KICA (WKICA). In particular, in WKICA, GMM is first adopted to estimate the probabilities of the KICs extracted by KICA. The significant KICs embodying the dominant process variation are then discriminated based on the estimated probabilities and assigned with larger weights to capture the significant information during online fault detection. A nonlinear contribution plots method is also developed based on the idea of a sensitivity analysis to help identifying the fault variables after a fault is detected. Simulation studies conducted on a simple four-variable nonlinear system and the Tennessee Eastman benchmark process demonstrate the superiority of the proposed method over the conventional KICA based method. PMID- 26685275 TI - HEp-2 Cell Classification via Combining Multiresolution Co-Occurrence Texture and Large Region Shape Information. AB - Indirect immunofluorescence imaging of human epithelial type 2 (HEp-2) cell image is an effective evidence to diagnose autoimmune diseases. Recently, computer aided diagnosis of autoimmune diseases by the HEp-2 cell classification has attracted great attention. However, the HEp-2 cell classification task is quite challenging due to large intraclass and small interclass variations. In this paper, we propose an effective approach for the automatic HEp-2 cell classification by combining multiresolution co-occurrence texture and large regional shape information. To be more specific, we propose to: 1) capture multiresolution co-occurrence texture information by a novel pairwise rotation invariant co-occurrence of local Gabor binary pattern descriptor; 2) depict large regional shape information by using an improved Fisher vector model with RootSIFT features, which are sampled from large image patches in multiple scales; and 3) combine both features. We evaluate systematically the proposed approach on the IEEE International Conference on Pattern Recognition (ICPR) 2012, the IEEE International Conference on Image Processing (ICIP) 2013, and the ICPR 2014 contest datasets. The proposed method based on the combination of the introduced two features outperforms the winners of the ICPR 2012 contest using the same experimental protocol. Our method also greatly improves the winner of the ICIP 2013 contest under four different experimental setups. Using the leave-one specimen-out evaluation strategy, our method achieves comparable performance with the winner of the ICPR 2014 contest that combined four features. PMID- 26685276 TI - Two Fast Complex-Valued Algorithms for Solving Complex Quadratic Programming Problems. AB - In this paper, we propose two fast complex-valued optimization algorithms for solving complex quadratic programming problems: 1) with linear equality constraints and 2) with both an l1 -norm constraint and linear equality constraints. By using Brandwood's analytic theory, we prove the convergence of the two proposed algorithms under mild assumptions. The two proposed algorithms significantly generalize the existing complex-valued optimization algorithms for solving complex quadratic programming problems with an l1 -norm constraint only and unconstrained complex quadratic programming problems, respectively. Numerical simulations are presented to show that the two proposed algorithms have a faster speed than conventional real-valued optimization algorithms. PMID- 26685277 TI - An Orthogonal Evolutionary Algorithm With Learning Automata for Multiobjective Optimization. AB - Research on multiobjective optimization problems becomes one of the hottest topics of intelligent computation. In order to improve the search efficiency of an evolutionary algorithm and maintain the diversity of solutions, in this paper, the learning automata (LA) is first used for quantization orthogonal crossover (QOX), and a new fitness function based on decomposition is proposed to achieve these two purposes. Based on these, an orthogonal evolutionary algorithm with LA for complex multiobjective optimization problems with continuous variables is proposed. The experimental results show that in continuous states, the proposed algorithm is able to achieve accurate Pareto-optimal sets and wide Pareto-optimal fronts efficiently. Moreover, the comparison with the several existing well-known algorithms: nondominated sorting genetic algorithm II, decomposition-based multiobjective evolutionary algorithm, decomposition-based multiobjective evolutionary algorithm with an ensemble of neighborhood sizes, multiobjective optimization by LA, and multiobjective immune algorithm with nondominated neighbor-based selection, on 15 multiobjective benchmark problems, shows that the proposed algorithm is able to find more accurate and evenly distributed Pareto optimal fronts than the compared ones. PMID- 26685278 TI - Dynamic IQC-Based Control of Uncertain LFT Systems With Time-Varying State Delay. AB - This paper presents a new exact-memory delay control scheme for a class of uncertain systems with time-varying state delay under the integral quadratic constraint (IQC) framework. The uncertain system is described as a linear fractional transformation model including a state-delayed linear time-invariant (LTI) system and time-varying structured uncertainties. The proposed exact-memory delay controller consists of a linear state-feedback control law and an additional term that captures the delay behavior of the plant. We first explore the delay stability and the L2 -gain performance using dynamic IQCs incorporated with quadratic Lyapunov functions. Then, the design of exact-memory controllers that guarantee desired L2 -gain performance is examined. The resulting delay control synthesis conditions are formulated in terms of linear matrix inequalities, which are convex on all design variables including the scaling matrices associated with the IQC multipliers. The IQC-based exact-memory control scheme provides a novel approach for delay control designs via convex optimization, and advances existing control methods in two important ways: 1) better controlled performance and 2) simplified design procedure with less computational cost. The effectiveness and advantages of the proposed approach have been demonstrated through numerical studies. PMID- 26685279 TI - Extending the Capture Volume of an Iris Recognition System Using Wavefront Coding and Super-Resolution. AB - Iris recognition has gained increasing popularity over the last few decades; however, the stand-off distance in a conventional iris recognition system is too short, which limits its application. In this paper, we propose a novel hardware software hybrid method to increase the stand-off distance in an iris recognition system. When designing the system hardware, we use an optimized wavefront coding technique to extend the depth of field. To compensate for the blurring of the image caused by wavefront coding, on the software side, the proposed system uses a local patch-based super-resolution method to restore the blurred image to its clear version. The collaborative effect of the new hardware design and software post-processing showed great potential in our experiment. The experimental results showed that such improvement cannot be achieved by using a hardware-or software-only design. The proposed system can increase the capture volume of a conventional iris recognition system by three times and maintain the system's high recognition rate. PMID- 26685280 TI - Reinforced Extreme Learning Machines for Fast Robust Regression in the Presence of Outliers. AB - Extreme learning machines (ELMs) are fast methods that obtain state-of-the-art results in regression. However, they are not robust to outliers and their meta parameter (i.e., the number of neurons for standard ELMs and the regularization constant of output weights for L2 -regularized ELMs) selection is biased by such instances. This paper proposes a new robust inference algorithm for ELMs which is based on the pointwise probability reinforcement methodology. Experiments show that the proposed approach produces results which are comparable to the state of the art, while being often faster. PMID- 26685281 TI - Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies. AB - BACKGROUND: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. OBJECTIVES: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). METHODS: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (SigmaDEP) and three dimethyl phosphate (SigmaDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (SigmaDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. RESULTS: We found no significant associations of SigmaDEP, SigmaDMP, or SigmaDAPs with birth weight, length, or head circumference overall. However, among non Hispanic black women, increasing urinary SigmaDAP and SigmaDMP concentrations were associated with decreased birth length (beta = -0.4 cm; 95% CI: -0.9, 0.0 and beta = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, SigmaDAP and SigmaDMP were negatively associated with length (beta = -0.4 cm; 95% CI: 0.9, 0.0 and beta = -0.5 cm; 95% CI: -0.9, -0.1). CONCLUSIONS: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. CITATION: Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084-1092; http://dx.doi.org/10.1289/ehp.1409362. PMID- 26685282 TI - The emerging role of noncoding RNA in prostate cancer progression and its implication on diagnosis and treatment. AB - Recent transcriptome studies using next-generation sequencing have detected aberrant changes in the expression of noncoding RNAs (ncRNAs) associated with cancer. For prostate cancer, the expression levels of ncRNAs including microRNAs and long noncoding RNAs are strongly associated with diagnosis, carcinogenesis and tumor growth. Moreover, androgen and its cognate receptor, androgen receptor (AR), regulate various signaling pathways for prostate tumor growth. In addition, progression to lethal castration-resistant prostate cancer (CRPC) is also owing to AR function. Systematic analysis of AR-binding sites and their regulated transcripts revealed that many ncRNAs are widely regulated at the transcriptional level. Thus, recent studies provide new insight into the complicated molecular mechanism of prostate cancer progression. This review focused on the role of various ncRNAs in prostate cancer and the association between their expression and CRPC. PMID- 26685284 TI - Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases. AB - BACKGROUND: Chrysotile asbestos accounts for > 90% of the asbestos used worldwide, and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies; however, the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these malignancies is represented by epithelial-mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to assume a mesenchymal phenotype. In the present work, we propose that chrysotile asbestos induces EMT through a mechanism involving a signaling pathway mediated by tranforming growth factor beta (TGF beta). OBJECTIVES: We investigated the role of chrysotile asbestos in inducing EMT in order to elucidate the molecular mechanisms involved in this event. METHODS: Human bronchial epithelial cells (BEAS-2B) were incubated with 1 MUg/cm2 chrysotile asbestos for <= 72 hr, and several markers of EMT were investigated. Experiments with specific inhibitors for TGF-beta, glycogen synthase kinase-3beta (GSK-3beta), and Akt were performed to confirm their involvement in asbestos induced EMT. Real-time polymerase chain reaction (PCR), Western blotting, and gelatin zymography were performed to detect mRNA and protein level changes for these markers. RESULTS: Chrysotile asbestos activated a TGF-beta-mediated signaling pathway, implicating the contributions of Akt, GSK-3beta, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in epithelial markers (E-cadherin and beta-catenin) and an increase in mesenchymal markers (alpha-smooth muscle actin, vimentin, metalloproteinases, and fibronectin). CONCLUSIONS: Our findings suggest that chrysotile asbestos induces EMT, a common event in asbestos-related diseases, at least in part by eliciting the TGF-beta-mediated Akt/GSK-3beta/SNAIL-1 pathway. CITATION: Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E. 2016. Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776-784; http://dx.doi.org/10.1289/ehp.1409627. PMID- 26685285 TI - A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases. AB - BACKGROUND: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. OBJECTIVES: We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2',4,4',5,5' hexachlorobiphenyl (PCB 153), and 4,4'-dichlorodiphenyldichloroethylene (p,p' DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. METHODS: For our searches, we used proprietary systems biology software (MetaCoreTM/MetaDrugTM) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. CONCLUSIONS: Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. CITATION: Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ Health Perspect 124:1034-1041; http://dx.doi.org/10.1289/ehp.1510308. PMID- 26685287 TI - Engaging Elderly People in Telemedicine Through Gamification. AB - BACKGROUND: Telemedicine can alleviate the increasing demand for elderly care caused by the rapidly aging population. However, user adherence to technology in telemedicine interventions is low and decreases over time. Therefore, there is a need for methods to increase adherence, specifically of the elderly user. A strategy that has recently emerged to address this problem is gamification. It is the application of game elements to nongame fields to motivate and increase user activity and retention. OBJECTIVE: This research aims to (1) provide an overview of existing theoretical frameworks for gamification and explore methods that specifically target the elderly user and (2) explore user classification theories for tailoring game content to the elderly user. This knowledge will provide a foundation for creating a new framework for applying gamification in telemedicine applications to effectively engage the elderly user by increasing and maintaining adherence. METHODS: We performed a broad Internet search using scientific and nonscientific search engines and included information that described either of the following subjects: the conceptualization of gamification, methods to engage elderly users through gamification, or user classification theories for tailored game content. RESULTS: Our search showed two main approaches concerning frameworks for gamification: from business practices, which mostly aim for more revenue, emerge an applied approach, while academia frameworks are developed incorporating theories on motivation while often aiming for lasting engagement. The search provided limited information regarding the application of gamification to engage elderly users, and a significant gap in knowledge on the effectiveness of a gamified application in practice. Several approaches for classifying users in general were found, based on archetypes and reasons to play, and we present them along with their corresponding taxonomies. The overview we created indicates great connectivity between these taxonomies. CONCLUSIONS: Gamification frameworks have been developed from different backgrounds-business and academia-but rarely target the elderly user. The effectiveness of user classifications for tailored game content in this context is not yet known. As a next step, we propose the development of a framework based on the hypothesized existence of a relation between preference for game content and personality. PMID- 26685286 TI - Assessing the Health Impact of Water Quality Interventions in Low-Income Settings: Concerns Associated with Blinded Trials and the Need for Objective Outcomes. AB - BACKGROUND: A dramatic disparity between the results of blinded versus open trial designs has raised questions about the effectiveness of water quality interventions and other environmental interventions to prevent diarrhea, a leading killer of young children in low-income countries. OBJECTIVES: We summarize the results of blinded versus open trials of water quality interventions, describe evidence from a recent placebo-controlled trial in India suggesting that control households were put at risk from their participation, and suggest alternatives to blinded trials that could resolve continued uncertainty about the magnitude of the protective effect of water, sanitation, and hygiene (WASH) interventions without presenting ethical questions. DISCUSSION: Concerns about reporting bias in open trial designs continue to cause uncertainty about the effectiveness of WASH interventions. However, evidence suggests that despite instructions to the contrary, placebos may encourage control group participants in blinded trials to cease practicing traditional water treatment practices in the mistaken belief that they are protected by an active intervention. Although objective outcomes such as pathogen incrimination, seroconversion, biomarkers, and anthropometry can be helpful, these are often costly, nonspecific, and unsuitable for evaluating programmatic interventions. CONCLUSIONS: Unless researchers can be assured that a placebo will not cause those in a control group to change their behavior in a manner that increases their risk, it is incumbent on researchers to use alternatives. Validated objective measures are needed for assessing the health impact of WASH interventions that are reliable, affordable, and suitable both for research and program evaluation. CITATION: Clasen T, Boisson S. 2016. Assessing the health impact of water quality interventions in low-income settings: concerns associated with blinded trials and the need for objective outcomes. Environ Health Perspect 124:886-889; http://dx.doi.org/10.1289/ehp.1510532. PMID- 26685283 TI - Noncoding RNAs in breast cancer. AB - The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics. PMID- 26685288 TI - A Community-Engaged Approach to Developing an mHealth HIV/STI and Drug Abuse Preventive Intervention for Primary Care: A Qualitative Study. AB - BACKGROUND: Despite ongoing prevention efforts, HIV and other sexually transmitted infections (HIV/STIs) and drug use remain public health concerns. Urban adolescents, many of whom are underserved and racial minorities, are disproportionately affected. Recent changes in policy, including the Affordable Care Act, and advances in technology provide HIV/STI and drug abuse prevention scientists with unique opportunities to deliver mobile health (mHealth) preventive interventions in primary care. OBJECTIVES: The purpose of this community-engaged study was to develop an mHealth version of the Storytelling for Empowerment preventive intervention for primary care (hereinafter referred to as "S4E"). METHODS: A total of 29 adolescents were recruited from a youth-centered primary care clinic in Southeast, Michigan, to participate in qualitative interviews. Participants were predominantly African American (n=19, 65.5%) and female (n=21, 72.4%) with a mean age of 16.23 (SD 2.09). The principles of community-based participatory research (CBPR), in conjunction with agile software development and the recommended core prevention principles of the National Institute on Drug Abuse (NIDA) were employed during S4E development. CBPR principles are aimed at improving the effectiveness of research by addressing locally relevant health problems, working with community strengths, and translating basic science into applied research. Complementing this approach, the NIDA prevention principles are derived from decades of drug abuse prevention research aimed at increasing the effectiveness and uptake of programs, through the development of culturally specific interventions and ensuring the structure, content, and delivery of the intervention fit the needs of the community. Data were analyzed using thematic analysis. RESULTS: A total of 5 themes emerged from the data: (1) acceptability of the mHealth app to adolescents in primary care, (2) inclusion of a risk assessment to improve clinician-adolescent HIV/STI and drug use communication, (3) incorporation of culturally specific HIV/STI and drug use content, (4) incorporation of interactive aspects in the app to engage youth, and (5) perspectives on the appearance of the app. CONCLUSIONS: There is a dearth of mHealth HIV/STI and drug abuse preventive interventions for primary care. Incorporating the principles of CBPR in conjunction with agile software development and NIDA-recommended core prevention principles may be helpful in developing culturally specific mHealth interventions. An important next step in this program of research is to examine the feasibility, acceptability, and efficacy of S4E on adolescent sexual risk and drug use behaviors, and HIV/STI testing. Implications for prevention research and primary care practice are discussed in the context of the Affordable Care Act and technological advances. PMID- 26685290 TI - Cardiac Resynchronization Therapy: A Review of Pathophysiology and Clinical Applications. PMID- 26685289 TI - The Effect of Patient-Specific Cerebral Oxygenation Monitoring on Postoperative Cognitive Function: A Multicenter Randomized Controlled Trial. AB - BACKGROUND: Indices of global tissue oxygen delivery and utilization such as mixed venous oxygen saturation, serum lactate concentration, and arterial hematocrit are commonly used to determine the adequacy of tissue oxygenation during cardiopulmonary bypass (CPB). However, these global measures may not accurately reflect regional tissue oxygenation and ischemic organ injury remains a common and serious complication of CPB. Near-infrared spectroscopy (NIRS) is a noninvasive technology that measures regional tissue oxygenation. NIRS may be used alongside global measures to optimize regional perfusion and reduce organ injury. It may also be used as an indicator of the need for red blood cell transfusion in the presence of anemia and tissue hypoxia. However, the clinical benefits of using NIRS remain unclear and there is a lack of high-quality evidence demonstrating its efficacy and cost effectiveness. OBJECTIVE: The aim of the patient-specific cerebral oxygenation monitoring as part of an algorithm to reduce transfusion during heart valve surgery (PASPORT) trial is to determine whether the addition of NIRS to CPB management algorithms can prevent cognitive decline, postoperative organ injury, unnecessary transfusion, and reduce health care costs. METHODS: Adults aged 16 years or older undergoing valve or combined coronary artery bypass graft and valve surgery at one of three UK cardiac centers (Bristol, Hull, or Leicester) are randomly allocated in a 1:1 ratio to either a standard algorithm for optimizing tissue oxygenation during CPB that includes a fixed transfusion threshold, or a patient-specific algorithm that incorporates cerebral NIRS monitoring and a restrictive red blood cell transfusion threshold. Allocation concealment, Internet-based randomization stratified by operation type and recruiting center, and blinding of patients, ICU and ward care staff, and outcome assessors reduce the risk of bias. The primary outcomes are cognitive function 3 months after surgery and infectious complications during the first 3 months after surgery. Secondary outcomes include measures of inflammation, organ injury, and volumes of blood transfused. The cost effectiveness of the NIRS-based algorithm is described in terms of a cost-effectiveness acceptability curve. The trial tests the superiority of the patient-specific algorithm versus standard care. A sample size of 200 patients was chosen to detect a small to moderate target difference with 80% power and 5% significance (two tailed). RESULTS: Over 4 years, 208 patients have been successfully randomized and have been followed up for a 3-month period. Results are to be reported in 2015. CONCLUSIONS: This study provides high-quality evidence, both valid and widely applicable, to determine whether the use of NIRS monitoring as part of a patient-specific management algorithm improves clinical outcomes and is cost effective. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 23557269; http://www.isrctn.com/ISRCTN23557269 (Archived by Webcite at http://www.webcitation.org/6buyrbj64). PMID- 26685291 TI - Aspirin for Primary Prevention of Cardiovascular Diseases: Current Concepts, Unanswered Questions and Future Directions. PMID- 26685292 TI - A Greek Prospective Observational Study of Cardiovascular Morbidity and Mortality in Patients with Atrial Fibrillation. AB - INTRODUCTION: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and represents a growing threat to public health. A representation of data among the private sector in Greece and an assessment of the correlation of different treatment strategies (rate or rhythm control) with annual cardiovascular (CV) morbidity and total mortality, are generally lacking. METHODS: Patients aged >18 years, diagnosed with AF verified by a standard electrocardiogram (ECG), were included in this observational study (n=1545). Information and data, including demographic characteristics, clinical profiles, therapeutic strategies and outcomes, were collected prospectively from each patient at 4 visits: baseline, 6+/-2, 12+/-2, and 24+/-2 months. Data were analyzed using descriptive statistics, quantitative and qualitative variables. RESULTS: The annual non-adjusted CV morbidity was 18.1% [95% CI 16.0-20.3%] and 17.2% [13.9-18.4%] in the first and second years, respectively. At the end of the first year, the non-adjusted CV morbidity was 17.1% [14.0-20.3%] for rhythm control treatment and 18.9% [15.9-21.8%] for rate-control treatment (p=0.477). At the end of the second year, the non-adjusted CV morbidity was 14.9% [11.6-18.2%] for rhythm-control treatment and 17.2% [14.1-20.2%] for rate-control treatment (p=0.367). Overall non-adjusted mortality was 1.6% [0.9-2.3%] and 1.9% [1.1-2.7%] in the first and second years, respectively. At the end of the first year, the non-adjusted mortality was 0.7% [0.02-1.5%] for rhythm-control treatment and 2.3% [1.9-3.4%] for rate-control treatment (p=0.030). At the end of the second year, the non-adjusted mortality was 0.6% [0-1.4%] for rhythm-control treatment and 2.8% [1.5-4.1%] for rate-control treatment (p=0.009). CONCLUSIONS: In this multi centre, countrywide, 24-month observational prospective study, there were no statistically significant differences in CV morbidity between rhythm and rate control treatments, whereas there were statistically significant differences in total mortality in the first and second years. Rhythm- versus rate-control treatment showed a lower rate of total mortality in both the first and second years. PMID- 26685293 TI - Rhythm or Rate Control Management of Atrial Fibrillation: An Overrated Dilemma. PMID- 26685294 TI - Relationship between Sympathetic Overactivity and Left Ventricular Hypertrophy in Resistant Hypertension. AB - INTRODUCTION: Sympathetic overactivity plays an important role in the development of resistant hypertension (RH). However, the effect of sympathetic predominance on left ventricular hypertrophy (LVH) in RH is not very clear. In our study, we aimed to evaluate the association between sympathetic overactivity and LVH in RH. METHODS: One hundred forty-two RH patients were enrolled in this study. Transthoracic echocardiography was performed in each case and LVH parameters (interventricular septum and posterior wall thickness, left ventricular mass and left ventricular mass index) were assessed. Seventy-five patients had echocardiographic evidence of LVH (RH/LVH(+)) while the other 67 patients did not (RH/LVH(-)). Mean heart rate and time domain heart rate variability (HRV) values standard deviation of NN intervals (SDNN), standard deviation of all five-minute NN intervals (SDANN), triangular index - that reflect sympathetic overactivity were obtained from 24-hour ECG recordings. Mean heart rate and HRV values were compared between the two groups. RESULTS: Demographic and clinical characteristics and blood pressure levels were similar between the groups. Echocardiographic parameters that reflect LVH were significantly higher in the RH/LVH(+) group than in the RH/LVH(-) group. Time domain HRV values were significantly lower (SDNN: 119.1 +/- 34.6 vs. 138.1 +/- 42.9, p=0.004; SDANN: 108.1 +/- 41.6 vs. 127.9 +/- 45.1, p=0.007; triangular index: 31.2 +/- 10.5 vs. 36.3 +/- 11.1, p=0.006) and mean heart rate was significantly higher (83.7 +/- 16.4 vs. 78.3 +/- 12.4, p=0.03) in the RH/LVH(+) group than in the RH/LVH(-) group. CONCLUSIONS: Our study showed that, among patients with RH, sympathetic overactivity is significantly higher in those with LVH. PMID- 26685295 TI - Sympathetic Nervous System Activation and Left Ventricular Hypertrophy: Reflections of the Same Portrait of Resistant Hypertension? PMID- 26685296 TI - Left Atrial Appendage Closure. Initial SingleCenter Experience with the Watchman Device. PMID- 26685297 TI - Are Left Ventricular Rotational Mechanics NonInverted in Situs Inversus Totalis? (A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study). PMID- 26685298 TI - Traumatic Tricuspid Insufficiency Requiring Valve Repair in an Acute Setting. AB - Tricuspid insufficiency due to penetrating cardiac trauma is rare. Patients with tricuspid insufficiency due to trauma can tolerate this abnormality for months or even years. We report a case of a 66-year-old female with penetrating cardiac trauma on the right side of her heart that required tricuspid valve repair in an acute setting. She sustained cut and stab wounds on her bilateral forearms and in the neck and epigastric region. She had cardiac tamponade and developed pulseless electrical activity, which required emergency surgery. The right ventricle and superior vena cava were dissected approximately 5 cm and 2 cm, respectively. After these wounds had been repaired, the patient's inability to wean from cardiopulmonary bypass suggested rightsided heart failure; transesophageal echocardiography revealed tricuspid insufficiency. Right atriotomy was performed, and a detailed examination revealed that the tricuspid valve septal leaflet was split in two. There was also an atrial septal injury that created a connection with the left atrium; these injuries were not detected from the right ventricular wound. After repair, weaning from cardiopulmonary bypass with mild tricuspid insufficiency was achieved, and she recovered uneventfully. This case emphasized the importance of thoroughly investigating intracardiac injury and transesophageal echocardiography. PMID- 26685299 TI - Right Ventricular Strain in Patients with Moderate Heart Failure. PMID- 26685300 TI - Left Internal Mammary Arterial Angiography Via the Right Radial Approach: Description of Technique, Single-Centre Experience, and Brief Review of the Literature. PMID- 26685301 TI - Acute Coronary Syndromes and Atrial Fibrillation. PMID- 26685302 TI - SPRINT Results Are Life-Saving, Guideline-Changing, and Hypertension Research Intensifying. PMID- 26685303 TI - A SIRT4-like auto ADP-ribosyltransferase is essential for the environmental growth of Mycobacterium smegmatis. AB - SIRT family proteins are highly conserved both in the structure and function among all the organisms, and are involved in gene silencing, DNA damage repair, cell growth and metabolism. Here, a SIRT4 homologue MSMEG_4620 was identified and characterized in Mycobacterium smegmatis. MSMEG_4620 exhibits deacetylase activity that can be activated by fatty acids. Interestingly, MSMEG_4620 also possesses auto ADP-ribosylation activity. MSMEG_4620 is modified on arginine residues as revealed by a chemical stability assay. Moreover, the auto ADP ribosylation activity of MSMEG_4620 was found to be enhanced by ferric ion. Notably, the SIRT4 homologues are widely distributed in the genomes of environmental mycobacterial species instead of pathogenic mycobacterial species. When MSMEG_4620 was deleted in M. smegmatis, the mutant strain showed a growth defect in 7H9 minimal medium compared with the parental strain. Taken together, these results provided the characteristics of a SIRT4 homologue in prokaryotes and implicated its critical roles in the growth of environmental mycobacterial species. PMID- 26685305 TI - FluxModeCalculator: an efficient tool for large-scale flux mode computation. AB - Elementary flux mode (EFM) analysis is a powerful technique for determining the metabolic capacities and robustness of stoichiometric networks. Recently, several improvements have been made to the algorithm for enumerating the EFMs, making the study of large models possible. However, currently these tools require high performance workstations to perform large-scale EFM computations, thus limiting their applicability. We developed a more time and memory efficient implementation of the algorithm for EFM enumeration in MATLAB, called FluxModeCalculator, which enables large-scale EFM computation on ordinary desktop computers. AVAILABILITY AND IMPLEMENTATION: FluxModeCalculator is open source and freely available under the terms of the GNU General Public License v3.0 at http://www.lumc.nl/jan-bert van-klinken CONTACT: j.b.van_klinken@lumc.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26685304 TI - Transcriptomics-based identification of WRKY genes and characterization of a salt and hormone-responsive PgWRKY1 gene in Panax ginseng. AB - WRKY proteins belong to a transcription factor (TF) family and play dynamic roles in many plant processes, including plant responses to abiotic and biotic stresses, as well as secondary metabolism. However, no WRKY gene in Panax ginseng C.A. Meyer has been reported to date. In this study, a number of WRKY unigenes from methyl jasmonate (MeJA)-treated adventitious root transcriptome of this species were identified using next-generation sequencing technology. A total of 48 promising WRKY unigenes encoding WRKY proteins were obtained by eliminating wrong and incomplete open reading frame (ORF). Phylogenetic analysis reveals 48 WRKY TFs, including 11 Group I, 36 Group II, and 1 Group III. Moreover, one MeJA responsive unigene designated as PgWRKY1 was cloned and characterized. It contains an entire ORF of 1077 bp and encodes a polypeptide of 358 amino acid residues. The PgWRKY1 protein contains a single WRKY domain consisting of a conserved amino acid sequence motif WRKYGQK and a C2H2-type zinc-finger motif belonging to WRKY subgroup II-d. Subcellular localization of PgWRKY1-GFP fusion protein in onion and tobacco epidermis cells revealed that PgWRKY1 was exclusively present in the nucleus. Quantitative real-time polymerase chain reaction analysis demonstrated that the expression of PgWRKY1 was relatively higher in roots and lateral roots compared with leaves, stems, and seeds. Importantly, PgWRKY1 expression was significantly induced by salicylic acid, abscisic acid, and NaCl, but downregulated by MeJA treatment. These results suggested that PgWRKY1 might be a multiple stress-inducible gene responding to hormones and salt stresses. PMID- 26685306 TI - PaxtoolsR: pathway analysis in R using Pathway Commons. AB - PURPOSE: PaxtoolsR package enables access to pathway data represented in the BioPAX format and made available through the Pathway Commons webservice for users of the R language to aid in advanced pathway analyses. Features include the extraction, merging and validation of pathway data represented in the BioPAX format. This package also provides novel pathway datasets and advanced querying features for R users through the Pathway Commons webservice allowing users to query, extract and retrieve data and integrate these data with local BioPAX datasets. AVAILABILITY AND IMPLEMENTATION: The PaxtoolsR package is compatible with versions of R 3.1.1 (and higher) on Windows, Mac OS X and Linux using Bioconductor 3.0 and is available through the Bioconductor R package repository along with source code and a tutorial vignette describing common tasks, such as data visualization and gene set enrichment analysis. Source code and documentation are at http://www.bioconductor.org/packages/paxtoolsr This plugin is free, open-source and licensed under the LGPL-3. CONTACT: paxtools@cbio.mskcc.org or lunaa@cbio.mskcc.org. PMID- 26685307 TI - traseR: an R package for performing trait-associated SNP enrichment analysis in genomic intervals. AB - Genome-wide association studies (GWASs) have successfully identified many sequence variants that are significantly associated with common diseases and traits. Tens of thousands of such trait-associated SNPs have already been cataloged, which we believe form a great resource for genomic research. Recent studies have demonstrated that the collection of trait-associated SNPs can be exploited to indicate whether a given genomic interval or intervals are likely to be functionally connected with certain phenotypes or diseases. Despite this importance, currently, there is no ready-to-use computational tool able to connect genomic intervals to phenotypes. Here, we present traseR, an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD. AVAILABILITY AND IMPLEMENTATION: The traseR R package preloaded with up-to-date collection of trait-associated SNPs are freely available in Bioconductor CONTACT: zhaohui.qin@emory.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26685308 TI - MSAcquisitionSimulator: data-dependent acquisition simulator for LC-MS shotgun proteomics. AB - Data-dependent acquisition (DDA) is the most common method used to control the acquisition process of shotgun proteomics experiments. While novel DDA approaches have been proposed, their evaluation is made difficult by the need of programmatic control of a mass spectrometer. An alternative is in silico analysis, for which suitable software has been unavailable. To meet this need, we have developed MSAcquisitionSimulator-a collection of C ++ programs for simulating ground truth LC-MS data and the subsequent application of custom DDA algorithms. It provides an opportunity for researchers to test, refine and evaluate novel DDA algorithms prior to implementation on a mass spectrometer. AVAILABILITY AND IMPLEMENTATION: The software is freely available from its Github repository http://www.github.com/DennisGoldfarb/MSAcquisitionSimulator/ which contains further documentation and usage instructions. CONTACT: weiwang@cs.ucla.edu or ben_major@med.unc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26685309 TI - Fast integration-based prediction bands for ordinary differential equation models. AB - MOTIVATION: To gain a deeper understanding of biological processes and their relevance in disease, mathematical models are built upon experimental data. Uncertainty in the data leads to uncertainties of the model's parameters and in turn to uncertainties of predictions. Mechanistic dynamic models of biochemical networks are frequently based on nonlinear differential equation systems and feature a large number of parameters, sparse observations of the model components and lack of information in the available data. Due to the curse of dimensionality, classical and sampling approaches propagating parameter uncertainties to predictions are hardly feasible and insufficient. However, for experimental design and to discriminate between competing models, prediction and confidence bands are essential. To circumvent the hurdles of the former methods, an approach to calculate a profile likelihood on arbitrary observations for a specific time point has been introduced, which provides accurate confidence and prediction intervals for nonlinear models and is computationally feasible for high-dimensional models. RESULTS: In this article, reliable and smooth point-wise prediction and confidence bands to assess the model's uncertainty on the whole time-course are achieved via explicit integration with elaborate correction mechanisms. The corresponding system of ordinary differential equations is derived and tested on three established models for cellular signalling. An efficiency analysis is performed to illustrate the computational benefit compared with repeated profile likelihood calculations at multiple time points. AVAILABILITY AND IMPLEMENTATION: The integration framework and the examples used in this article are provided with the software package Data2Dynamics, which is based on MATLAB and freely available at http://www.data2dynamics.org CONTACT: helge.hass@fdm.uni-freiburg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26685310 TI - Hierarchical block matrices as efficient representations of chromosome topologies and their application for 3C data integration. AB - MOTIVATION: Recent advancements in molecular methods have made it possible to capture physical contacts between multiple chromatin fragments. The resulting association matrices provide a noisy estimate for average spatial proximity that can be used to gain insights into the genome organization inside the nucleus. However, extracting topological information from these data is challenging and their integration across resolutions is still poorly addressed. Recent findings suggest that a hierarchical approach could be advantageous for addressing these challenges. RESULTS: We present an algorithmic framework, which is based on hierarchical block matrices (HBMs), for topological analysis and integration of chromosome conformation capture (3C) data. We first describe chromoHBM, an algorithm that compresses high-throughput 3C (HiT-3C) data into topological features that are efficiently summarized with an HBM representation. We suggest that instead of directly combining HiT-3C datasets across resolutions, which is a difficult task, we can integrate their HBM representations, and describe chromoHBM-3C, an algorithm which merges HBMs. Since three-dimensional (3D) reconstruction can also benefit from topological information, we further present chromoHBM-3D, an algorithm which exploits the HBM representation in order to gradually introduce topological constraints to the reconstruction process. We evaluate our approach in light of previous image microscopy findings and epigenetic data, and show that it can relate multiple spatial scales and provide a more complete view of the 3D genome architecture. AVAILABILITY AND IMPLEMENTATION: The presented algorithms are available from: https://github.com/yolish/hbm CONTACT: ys388@cam.ac.uk or pl219@cam.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26685312 TI - CCR7: Unifying Disparate Journeys to the Lymph Node. PMID- 26685311 TI - Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint. AB - During mitotic arrest induced by microtubule targeting drugs, the weakening of the spindle assembly checkpoint (SAC) allows cells to progress through the cell cycle without chromosome segregation occurring. PLK1 kinase plays a major role in mitosis and emerging evidence indicates that PLK1 is also involved in establishing the checkpoint and maintaining SAC signalling. However, mechanistically, the role of PLK1 in the SAC is not fully understood, with several recent reports indicating that it can cooperate with either one of the major checkpoint kinases, Aurora B or MPS1. In this study, we assess the role of PLK1 in SAC maintenance. We find that in nocodazole-arrested U2OS cells, PLK1 activity is continuously required for maintaining Aurora B protein localisation and activity at kinetochores. Consistent with published data we find that upon PLK1 inhibition, phosphoThr3-H3, a marker of Haspin activity, is reduced. Intriguingly, Aurora B inhibition causes PLK1 to relocalise from kinetochores into fewer and much larger foci, possibly due to incomplete recruitment of outer kinetochore proteins. Importantly, PLK1 inhibition, together with partial inhibition of Aurora B, allows efficient SAC override to occur. This phenotype is more pronounced than the phenotype observed by combining the same PLK1 inhibitors with partial MPS1 inhibition. We also find that PLK1 inhibition does not obviously cooperate with Haspin inhibition to promote SAC override. These results indicate that PLK1 is directly involved in maintaining efficient SAC signalling, possibly by cooperating in a positive feedback loop with Aurora B, and that partially redundant mechanisms exist which reinforce the SAC. PMID- 26685313 TI - Pillars Article: CCR7 Coordinates the Primary Immune Response by Establishing Functional Microenvironments in Secondary Lymphoid Organs. Cell. 1999. 99: 23-33. PMID- 26685314 TI - Hepatocytes as Immunological Agents. AB - Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID- 26685316 TI - Correction: Multiple Cathepsins Promote Pro-IL-1beta Synthesis and NLRP3-Mediated IL-1beta Activation. PMID- 26685317 TI - Demographic Parameters of Nezara viridula (Heteroptera: Pentatomidae) Reared on Two Diets Developed for Lygus spp. AB - Two artificial diets developed for rearing Lygus spp., a fresh yolk chicken egg based-diet (FYD) and a dry yolk chicken egg based-diet (DYD), were evaluated as an alternative food source for rearing the southern green stink bug, Nezara viridula (L.) (Heteroptera: Pentatomidae). Survival to adult was 97.3 and 74.67%, respectively, on the fresh and dry yolk diets. Insects fed FYD had 100% survival of nymphs from first through fourth instars. Adult development was significantly shorter on FYD (30.37 +/- SE 0.30 d) as compared with DYD (32.77 +/- SE 0.16 d). Increased male and female longevity, higher fecundity, and larger egg mass sizes were also observed with N. viridula-fed FYD. However, fertility and hatchability was higher on DYD. A complete cohort life table was constructed to describe the development of N. viridula on both diets. PMID- 26685315 TI - Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation. AB - Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the accumulation of Be-responsive CD4(+) T cells in the lung, and genetic susceptibility is primarily linked to HLA-DPB1 alleles possessing a glutamic acid at position 69 of the beta-chain. Recent structural analysis of a Be-specific TCR interacting with a Be-loaded HLA-DP2-peptide complex revealed that Be is coordinated by amino acid residues derived from the HLA-DP2 beta-chain and peptide and showed that the TCR does not directly interact with the Be(2+) cation. Rather, the TCR recognizes a modified HLA-DP2-peptide complex with charge and conformational changes. Collectively, these findings provide a structural basis for the development of this occupational lung disease through the ability of Be to induce posttranslational modifications in preexisting HLA-DP2-peptide complexes, resulting in the creation of neoantigens. PMID- 26685319 TI - The validity and reliability of the Korean version of the Cancer-chemotherapy Concerns Rating Scale. AB - OBJECTIVE: The Cancer-chemotherapy Concerns Rating Scale was developed in Japan for outpatients undergoing chemotherapy, and its validity and reliability have been reported. The purpose of the study was to test the reliability and validity of the Korean version of the Cancer-chemotherapy Concerns Rating Scale. METHODS: The questionnaire was filled out by 199 cancer patients, who were currently undergoing outpatient chemotherapy. The data were analyzed using exploratory factor analysis with Promax Rotation to determine the factor construct validity. The reliability of the Cancer-chemotherapy Concerns Rating Scale was investigated by Cronbach's alpha and the Spearman Brown coefficient. RESULTS: Four factors were obtained and the overall structure was similar to that of the Japanese version; reorganization of daily life, self-existence, disease progress, and social and economic concerns. Cronbach's alpha for the total scale was 0.91 and the Spearman Brown coefficient was 0.85. CONCLUSIONS: We found that the Korean version of the Cancer-chemotherapy Concerns Rating Scale could be clinically useful. It could provide health-care providers with information useful to understand the psychological state of patients undergoing outpatient chemotherapy. PMID- 26685318 TI - Phase I clinical trial of oral administration of S-1 in combination with intravenous gemcitabine and cisplatin in patients with advanced biliary tract cancer. AB - OBJECTIVE: This study aimed to determine the maximum tolerated dose and the recommended dose of combining S-1 with gemcitabine and cisplatin for advanced biliary tract adenocarcinoma first-line therapy. METHODS: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic biliary tract adenocarcinoma were enrolled. Patients with advanced biliary tract adenocarcinoma received gemcitabine and cisplatin intravenously on Days 1 and 8 and S-1 orally twice daily from Days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week), cisplatin (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/25/40 (level 0), 1000/25/40 (level 1), 1000/25/60 (level 2) and 1000/25/80 (level 3). Level 1 was chosen as the starting dose. For cases where recommended dose could not be determined within the triweekly schedule, we prepared a biweekly schedule to find recommended dose. RESULTS: Seventeen patients with advanced biliary tract adenocarcinoma were treated across three dose levels. Maximum tolerated dose and recommended dose were defined as level 0. Dose-limiting toxicities included a Grade 3 maculopapular rash, Grade 4 thrombocytopenia and consecutive administration skips of gemcitabine and cisplatin on Day 8. Five partial responses were observed. CONCLUSIONS: This triweekly triplet regimen was well tolerated and showed promising antitumor activity in patients with advanced biliary tract adenocarcinoma. We recommend level 0, gemcitabine at 800 mg/m(2)/week, cisplatin at 25 mg/m(2)/week and S-1 at 40 mg/m(2)/day during a 21-day cycle, in further studies with this schedule. PMID- 26685320 TI - Multicenter questionnaire survey on patterns of care for elderly patients with esophageal squamous cell carcinoma by the Japan Esophageal Oncology Group. AB - OBJECTIVE: There is little information about the patterns of care for elderly esophageal squamous cell carcinoma patients, and a standardized strategy has not been established. Therefore, we conducted a questionnaire survey about the patterns of care for these patients. METHODS: On September 2014, the questionnaires were sent to all 43 institutions of the Japan Esophageal Oncology Group, which comprised five parts: (i) definition of 'elderly' (age, method), (ii) basic treatment strategy according to stage and elderly status (fit/vulnerable/frail), (iii) patterns of care in each stage, (iv) considerations about conducting future clinical trials and (v) other information about geriatric oncology concerning esophageal squamous cell carcinoma. RESULTS: All answers were obtained by January 2015. Nearly half institutions (47%) considered the chronological definition of elderly to be over 80 years old. Among 43 institutions, 36 (84%) reported that the type of comorbidity and performance status were important factors for decision-making; no institution selected geriatric scale as an indicator. The most selected treatment strategy in fit healthy elderly patients was the same as the standard treatment of non-elderly patients. Radiation alone was considered the main treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Most of the institutions answered that clinical trials for the elderly are warranted. Most institutions (70%) chose Stage II/III (non-T4) esophageal squamous cell carcinoma as an important investigational target. CONCLUSIONS: Fit healthy elderly were considered the same as non-elderly patients, although there are no established treatment selection criteria. Radiation alone plays most important role in the treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Stage II/III (non-T4) disease is attractive and warranted for future investigations. PMID- 26685321 TI - Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. AB - OBJECTIVE: There have been few cost-effectiveness analyses of population-based colorectal cancer screening in Japan, and there is no consensus on the optimal use of total colonoscopy and the fecal immunochemical test for colorectal cancer screening with regard to cost-effectiveness and total colonoscopy workload. The present study aimed to examine the cost-effectiveness of colorectal cancer screening using Japanese data to identify the optimal use of total colonoscopy and fecal immunochemical test. METHODS: We developed a Markov model to assess the cost-effectiveness of colorectal cancer screening offered to an average-risk population aged 40 years or over. The cost, quality-adjusted life-years and number of total colonoscopy procedures required were evaluated for three screening strategies: (i) a fecal immunochemical test-based strategy; (ii) a total colonoscopy-based strategy; (iii) a strategy of adding population-wide total colonoscopy at 50 years to a fecal immunochemical test-based strategy. RESULTS: All three strategies dominated no screening. Among the three, Strategy 1 was dominated by Strategy 3, and the incremental cost per quality-adjusted life years gained for Strategy 2 against Strategies 1 and 3 were JPY 293 616 and JPY 781 342, respectively. Within the Japanese threshold (JPY 5-6 million per QALY gained), Strategy 2 was the most cost-effective, followed by Strategy 3; however, Strategy 2 required more than double the number of total colonoscopy procedures than the other strategies. CONCLUSIONS: The total colonoscopy-based strategy could be the most cost-effective for population-based colorectal cancer screening in Japan. However, it requires more total colonoscopy procedures than the other strategies. Depending on total colonoscopy capacity, the strategy of adding total colonoscopy for individuals at a specified age to a fecal immunochemical test based screening may be an optimal solution. PMID- 26685322 TI - Radiotherapy and gemcitabine-docetaxel chemotherapy in children and adolescents with unresectable recurrent or refractory osteosarcoma. AB - OBJECTIVE: Few reports have described the treatment outcome of osteosarcoma using radiotherapy. We evaluated the efficacy of radiotherapy and gemcitabine and docetaxel chemotherapy for patients with unresectable recurrent or refractory osteosarcoma. METHODS: Data from six patients (five male, one female) who received radiotherapy and gemcitabine and docetaxel chemotherapy at the Korea Cancer Center Hospital were retrospectively reviewed. Tumor response was evaluated according to metabolic changes using (18)F-fluorodeoxy-D-glucose positron emission tomography. RESULTS: The median age of the patients was 15.0 years (range, 14.0-15.8 years). Two patients had single bone lesions, and four had multiple metastatic bone lesions. Patients received a median 3.5 courses of gemcitabine and docetaxel chemotherapy (range, 2-6 courses). The median dose of radiotherapy was 50.0 Gy (range, 46-84 Gy). There were two complete metabolic responses and one partial metabolic response. The objective response rate was 50.0% (3/6). Responses were maintained for 4.6, 6.1 and 13.7 months, respectively. Patients were followed up for a median of 5.8 months (range, 2.7 84.6 months), and the median progression-free survival after this treatment was 3.6 months (range, 1.1-13.7 months). At the time of analysis, two patients were alive, one was lost to follow-up and three had died. CONCLUSION: Radiotherapy with gemcitabine and docetaxel chemotherapy showed some improvement in cases of refractory tumors or multiple bone metastases. Further studies are needed to investigate the efficacy of newer radiotherapy modalities, as well as to identify new radiosensitizing chemotherapy regimens. PMID- 26685323 TI - Study on the psychosocial aspects of risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers in Japan: a preliminary report. AB - OBJECTIVE: This study investigated the psychosocial aspects of risk-reducing salpingo-oophorectomy in Japan. METHODS: The subjects were 16 patients who underwent risk-reducing salpingo-oophorectomy at the Cancer Institute Hospital. Worry about cancer, emotional state and cancer-specific distress level were evaluated using a four-point Likert scale, the Profile of Mood States-Short Form and the Impact of Event Scale-Revised, respectively, before and 1 year after the surgery. In addition, the subjects were interviewed regarding their expectation for the risk-reducing surgery, the effects of the surgery, and the recovery from surgery, before the surgery and at 1, 6 and 12 months after the surgery. A t-test or Wilcoxon rank-sum test was used for the analysis, and literal analects were prepared for the interview and the answers were organized per question item using NVIVO10. RESULTS: The results revealed that the total score for worry about breast cancer and ovarian cancer (P = 0.021) as well as the Impact of Event Scale Revised (P = 0.021) were significantly lower 1 year after surgery, compared with the values before the surgery. Regarding the preoperative expectations for the surgery, the expectation for reducing the cancer risk was the highest. The reported effects of risk-reducing salpingo-oophorectomy on life included the appearance of menopausal symptoms, a loss of motivation and poor concentration; more effects were reported at 1 year after surgery than at 6 months after surgery. CONCLUSIONS: These results suggest that risk-reducing salpingo oophorectomy can be effective for reducing worry about breast cancer and ovarian cancer and cancer-specific distress as well as contributing to a reduction in mortality from fallopian tube and ovarian related cancer. PMID- 26685324 TI - The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer. AB - Stage IA non-small-cell lung cancer cases have been recognized as having a low risk of relapse; however, occasionally, relapse may occur. To predict clinical outcome in Stage IA non-small-cell lung cancer patients, we searched for chimeric transcripts that can be used as biomarkers and identified a novel chimeric transcript, RUNX1-GLRX5, comprising RUNX1, a transcription factor, and GLRX5. This chimera was detected in approximately half of the investigated Stage IA non small-cell lung cancer patients (44/104 cases, 42.3%). Although there was no significant difference in the overall survival rate between RUNX1-GLRX5-positive and -negative cases (P = 0.088), a significantly lower relapse rate was observed in the RUNX1-GLRX5-positive cases (P = 0.039), indicating that this chimera can be used as a biomarker for good prognosis in Stage IA patients. Detection of the RUNX1-GLRX5 chimeric transcript may therefore be useful for the determination of a postoperative treatment plan for Stage IA non-small-cell lung cancer patients. PMID- 26685325 TI - A Caenorhabditis elegans model for ether lipid biosynthesis and function. AB - Ether lipids are widespread in nature, and they are structurally and functionally important components of membranes. The roundworm, Caenorhabditis elegans, synthesizes numerous lipid species containing alkyl and alkenyl ether bonds. We isolated C. elegans strains carrying loss-of-function mutations in three genes encoding the proteins required for the initial three steps in the ether lipid biosynthetic pathway, FARD-1/FAR1, ACL-7/GNPAT, and ADS-1/AGPS. Analysis of the mutant strains show that they lack ether lipids, but possess the ability to alter their lipid composition in response to lack of ether lipids. We found that increases in de novo fatty acid synthesis and reduction of stearoyl- and palmitoyl-CoA desaturase activity, processes that are at least partially regulated transcriptionally, mediate the altered lipid composition in ether lipid deficient mutants. Phenotypic analysis demonstrated the importance of ether lipids for optimal fertility, lifespan, survival at cold temperatures, and resistance to oxidative stress.Caenorhabditis. PMID- 26685328 TI - Academician Ladislav MACHO, MD., PhD., D.Sci. 85th Anniversary. PMID- 26685329 TI - What are the personality traits associated with treatment adherence and non adherence? PMID- 26685326 TI - SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. AB - Cholesterol and fatty acid biosynthesis are regulated by the sterol regulatory element-binding proteins (SREBPs), encoded by Srebf1 and Srebf2. We generated mice that were either deficient or hypomorphic for SREBP-2. SREBP-2 deficiency generally caused death during embryonic development. Analyses of Srebf2(-/-) embryos revealed a requirement for SREBP-2 in limb development and expression of morphogenic genes. We encountered only one viable Srebf2(-/-) mouse, which displayed alopecia, attenuated growth, and reduced adipose tissue stores. Hypomorphic SREBP-2 mice (expressing low levels of SREBP-2) survived development, but the female mice exhibited reduced body weight and died between 8 and 12 weeks of age. Male hypomorphic mice were viable but had reduced cholesterol stores in the liver and lower expression of SREBP target genes. Reduced SREBP-2 expression affected SREBP-1 isoforms in a tissue-specific manner. In the liver, reduced SREBP-2 expression nearly abolished Srebf1c transcripts and reduced Srebf1a mRNA levels. In contrast, adipose tissue displayed normal expression of SREBP target genes, likely due to a compensatory increase in Srebf1a expression. Our results establish that SREBP-2 is critical for survival and limb patterning during development. Reduced expression of SREBP-2 from the hypomorphic allele leads to early death in females and reduced cholesterol content in the liver, but not in adipose tissue. PMID- 26685330 TI - Housing should be seen as critical part of health care. PMID- 26685327 TI - Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis. AB - Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understanding of its causes. The Cohorts for Heart and Aging Research in Genetic Epidemiology extra coronary calcium consortium reported a genome-wide association study demonstrating that genetic variants in LPA are strongly associated with aortic valve (AV) calcium and clinical AS. Using a Mendelian randomization study design, it was demonstrated that the effect of this genetic variant is mediated by plasma lipoprotein (a) [Lp(a)], directly implicating elevations in Lp(a) as a cause of AV calcium and progression to AS. This discovery has sparked intense interest in Lp(a) as a modifiable cause for AV disease. Herein, we will review the mounting epidemiological and genetic findings in support of Lp(a)-mediated valve disease, discuss potential mechanisms underlying this observation, and outline the steps to translate this discovery to a much needed novel preventive and/or therapeutic strategy for AV disease. PMID- 26685331 TI - 6 low-cost or no-cost home modifications to avoid falls. A few inexpensive changes in the home can lead to fewer injuries from falls each year. PMID- 26685332 TI - Ask the doctor. Does using a microwave to cook ruin the nutrients in food? PMID- 26685334 TI - Going wireless: the promise of leadless pacemakers. Tiny implants have the potential to normalize heart rhythms without the complications of traditional pacing devices. PMID- 26685333 TI - What common drugs may interfere with your heart medications? Over-the-counter cold and flu medicines can be especially challenging to manage if you take blood pressure medications or have an arrhythmia. PMID- 26685335 TI - Zeroing in on Amyotrophic lateral sclerosis. A look at a new era of ALS research. PMID- 26685336 TI - Metabolic syndrome: navigating a danger zone of heart risk factors. PMID- 26685337 TI - Combating chronic constipation...before it becomes an emergency. PMID- 26685338 TI - Study suggests tai chi improves life for people with chronic health problems. PMID- 26685339 TI - High olive oil consumption linked to lower breast cancer risk. PMID- 26685340 TI - Transition of care for HIV-infected youth can be challenging for both provider and patient. PMID- 26685341 TI - The important role of interdisciplinary care teams in comprehensive HIV medical care. PMID- 26685342 TI - Uncovering a pancreatic cyst: cause for concern? PMID- 26685343 TI - Treating spinal stenosis: physical therapy versus surgery. PMID- 26685345 TI - Active older men live longer. PMID- 26685344 TI - Injections don't improve physical therapy for knees. PMID- 26685347 TI - Harvard study links depression to stroke. PMID- 26685346 TI - Moderate alcohol consumption associated with heart problem. PMID- 26685348 TI - Do bone-building drugs really prevent hip fracture? PMID- 26685349 TI - Stopping estrogen therapy may bring back the blues for some women. PMID- 26685350 TI - Do blood pressure drugs raise your risk of a fall? PMID- 26685351 TI - Moderate drinking may harm older people's hearts. PMID- 26685352 TI - Can we improve care for HIV-infected youth along the HIV care continuum? PMID- 26685353 TI - Holistic law: a nexus of public health and legal services. PMID- 26685354 TI - Sex trade. Earlier entry into Mexico sex trade increases HIV. PMID- 26685355 TI - Treatment. Early ART reduces transmission, non-AIDS related health issues. PMID- 26685356 TI - Study gives new insights into obesity and breast cancer. PMID- 26685357 TI - Exercise prevents serious injuries in women who fall. PMID- 26685359 TI - Coronary artery calcium score may predict odds of dying. PMID- 26685358 TI - Higher blood levels of unsaturated fats linked to longer life. PMID- 26685360 TI - Snacks: quality vs. frequency. PMID- 26685361 TI - Tai chi: one-stop shopping for better balance and thinking skills. PMID- 26685362 TI - Breakfast-skippers: don't forget your fruits and grains. PMID- 26685363 TI - Survival of the fittest: men at 100 are healthier than women. PMID- 26685364 TI - Volunteering: giving and getting. PMID- 26685365 TI - Creature comforts: why your pet is good for your health. PMID- 26685366 TI - Secondhand smoke boosts stroke risk. PMID- 26685367 TI - Low-dose aspirin for people with heart disease. PMID- 26685368 TI - Exercise: a promising treatment for dementia? PMID- 26685369 TI - Minimum Value of Eligible Employer-Sponsored Plans and Other Rules Regarding the Health Insurance Premium Tax Credit. Final regulations. AB - This document contains final regulations on the health insurance premium tax credit enacted by the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010, as amended by the Medicare and Medicaid Extenders Act of 2010, the Comprehensive 1099 Taxpayer Protection and Repayment of Exchange Subsidy Overpayments Act of 2011, and the Department of Defense and Full-Year Continuing Appropriations Act, 2011. These final regulations affect individuals who enroll in qualified health plans through Affordable Insurance Exchanges (Exchanges, sometimes called Marketplaces) and claim the health insurance premium tax credit, and Exchanges that make qualified health plans available to individuals and employers. PMID- 26685370 TI - Should postmenopausal women boost their aerobic exercise time? PMID- 26685371 TI - Survey finds men don't use enough sunscreen. PMID- 26685373 TI - Vigorous exercise may counter cognitive decline in early Alzheimer's. PMID- 26685372 TI - New findings on statin--memory loss link. PMID- 26685374 TI - Increased mammography may mean more breast cancers found but no fewer deaths. PMID- 26685375 TI - A better way to predict fatal heart events. PMID- 26685376 TI - Longer work hours may boost stroke risk. PMID- 26685377 TI - Working overtime may raise stroke risk. PMID- 26685378 TI - Analysis raises new questions about treating noninvasive breast cancer. PMID- 26685379 TI - Injuries are up among older cyclists. PMID- 26685380 TI - Spicy foods associated with longer life, Harvard researchers find. PMID- 26685381 TI - Flu-fighting drugs don't prevent spread to others. PMID- 26685382 TI - Even a little daily exercise is good for healthy aging. PMID- 26685384 TI - Vitamin C may help protect you against cardiovascular disease. Research shows that a diet rich in fruits and vegetables lowers your risk of developing heart disease, and provides many other health benefits. PMID- 26685383 TI - Hypertension linked to frequent dining out. Big portions and too much sodium are largely to blame, but there are some heart-healthy strategies to dining out. PMID- 26685385 TI - The role of red cell genotyping in transfusion medicine. PMID- 26685386 TI - 3-D Printed Pills: A New Age for Drug Delivery. PMID- 26685387 TI - It Is Diversity of Experience That Counts. PMID- 26685388 TI - Autism: Historic View and a Current Biomedical Engineering Approach. PMID- 26685389 TI - Opportunities to Identify Unmet Needs Outside of the Operating Room. PMID- 26685390 TI - Meeting of the Strategic Advisory Group of Experts on immunization, October 2015 conclusions and recommendations. PMID- 26685391 TI - Soil-transmitted helminthiases: number of children treated in 2014. PMID- 26685392 TI - Monthly report on dracunculiasis cases, January-October 2015. PMID- 26685393 TI - [The role of Nods like receptors in the patients with allergic rhinitis]. AB - OBJECTIVE: To explore role of Nods (nucleotide-binding oligomerization domain Nod Like receptors) kind of pattern recognition receptors (PRR) in patients with allergic rhinitis. METHOD: The mRNA and protein of Nod1, Nod2 of Nalp3 were analyzed in the turbinate mucosa of patients with allergic rhinitis, nasal septum deviation (NSD) nasal mucosa of patients and nasal polyp mucosa with Real-Time RT PCR, Western blot and immunohistochemistry respectively, and Nod1 expression changes was explored in PBMC with wad explored Western-blot and then the level of IL-4, IL-6, IL-10, IFN-gamma were detected in serum of AR after desensitization treatment. RESULT: These Nods like receptors, mainly found in nasal mucosa epithelial cells, glandular epithelium and inflammatory cells (e. g. plasma cells, eosinophils), were expressed in the nasal mucosa tissues. In AR group, Nod1 (mRNA and protein) expression were lower than NSD group (P<0.05), Nalp3 expression were higher than (P<0.05), while, there was no significant difference of Nod2 (mRNA and protein) between groups. After 6 months desensitization therapy, the change of Nod1 in PBMC was negatively correlated with the change of IL-10 in the peripheral blood, r=-0.88, P<0.05; while, change of Nod1 was positively correlated, with the change of IL-6, r=0.57, P>0.05. CONCLUSION: Nod1, Nod2 and Nalp3 expression were seen in the two groups,and the Nod1 expression in allergic rhinitis group was lower than other two groups, while, the Nalp3 was higher than other two groups. It showed Nod1, Nalp3 may be involved in the pathogenesis of allergic rhinitis. Expression of Nod1 in PBMC reduced after sublingual desensitization treatment. Besides, the change of Nod1 was negatively correlated with the change of IL-10 in PBMC. So,it seemed that Nod1 may regulate IL-10 changes and be involved in sublingual desensitization therapy. PMID- 26685394 TI - [Analysis on allergens in patients with allergic rhinitis in Urumqi Xinjiang]. AB - OBJECTIVE: Understand the main types and characteristics of inhaled allergens in allergic rhinitis patients in Urumqi, Xinjiang, and provide theoretical basis for diagnosis, treatment, prevention of local allergic rhinitis and epidemiological investigation. METHOD: Inhaled allergen detecting on suspected patients with allergic rhinitis in clinic by the allergopharma skin prick test. Group the skin prick test positive patients of 340 samples according to their nationality, age and gender, then compare the inhaled allergen differences between them. RESULT: The total positive rate with allergic rhinitis prick test in 340 cases is 94.7%, of which the highest proportion is Artemisia (66.2%), followed by Chenopodium album (51.2%), poplar (42.6%), Ulmus (40.9%), Liu (33.8%), Timothy (27.6%), dust mite (21.2%), house dust mite (17.9%), ragweed (15.9%), dog (11.2%), cat (10.6%), cockroach (8.5%), Alternaria (5.6%) and Candida albicans (3.5%). The sensitivity of poplar, willow, Timothy and Alternaria of the minority group is higher than the Han group (P<0.05). The allergen positive rate difference among different age group has statistical significance (Chi2=59.076, P<0.01). CONCLUSION: Artemisia, Chenopodiaceae, poplar and elm are the main allergens in Urumqi area. There is a difference in allergen sensitivity between Minority and Han nationality patients. There is no statistical significance on inhaled allergen positive rate between different genders. Specific allergens can provide basis for the prevention and control of allergic diseases in Urumqi area. PMID- 26685395 TI - [Survey on the prevalence of childhood allergic rhinitis in Yinchuan]. AB - OBJECTIVE: To investigate the epidemic features of childhood allergic rhinitis (AR) and correlative risk factors in Yinchuan. METHOD: A questionnaire survey on AR was conducted among 800 children in eight communities, aged from 5 to 14 years old, by random cluster sampling, from March 2012 to March 2013 in Yinchuan. Suspects of AR, as identified by the survey, were recommended to specialist examinations for accurate diagnosis. The results were statistically analyzed. RESULT: Seven hundred and sixteen questionnaires were returned and 662 questionnaires were available. The prevalence rate of AR in children aged from 5 to 14 is 14.65% in Yinchuan. Seventy-nine point thirty-eight percent children suffered from intermittent AR, while 20.61% children suffered from persistent AR. The difference of prevalence between female (13.57%) and male (15.44%) was insignificant statistically (Chi2=0.454, P>0.05). The difference of prevalence between the Han (15.72%) and the Hui (11.35%) insignificant statistically (Chi2=2.055, P>0.05). The prevalence of AR children aged five to nine years was 13.80%, as aged ten to fourteen years was 19.72%. There was a significante differece between two groups (Chi2=4.056, P<0.05). The most explosive outbreak month in children with allergic rhinitis was July to September. The most common allergens found in patients were seasonal plants: mugwort, weed, dandelion, cereal, locust, ragweed, and willow. Fifteen point forty-six percent patients with AR also had rhinitic, 14.43% patients had asthma and 14.43% patients had allergic conjunctivitis. The history of drug allergy accounted for 12.37% in patients with AR, and food allergy accounted for 26.80%. In allergic rhinitis risk factors, family history accounted for 30.92%, non-breastfeeding representing accounted for 34.02%, animal feeding history accounted for 19.59%; exposure to passive smoking accounted for 42.26%; domestic decoration accounted for 12.37%. There were significante difference between AR children and normal in family history and non-breastfeeding (P<0.05). CONCLUSION: The prevalence rate of AR in children aged from 5 to 14 in Yinchuan is 14.45%. Strategy of prevention and treatment of AR should be worked out according to the epidemic feature of AR. PMID- 26685396 TI - [The influence of allergic rhinitis on negative emotion]. AB - OBJECTIVE: To investigate the influence of allergic rhinitis on negative emotion. METHOD: One hundred and ninety cases with allergic rhinitis as observer group were investigated by state-trait anxiety inventory (STAI) and self-rating depressive scale (SDS). According to pathogenetic condition, patients were divided into persistent allergic rhinitis 71 cases (A group) and intermittent allergic rhinitis 119 cases (B group). Meanwhile, 190 healthy persons as control group were compared with observer group. RESULT: (1) The main allergens of allergic rhinitis were dermatophagoides pteronyssinus, dermatophagoides farina, pollen, and epiphyte, which the skin index was above "++" by skin prick test. (2) The state anxiety score of observer group (42.17+/-16.21) was significantly higher than control group (38.78+/-16.54), t=2.02, P<0.05. There were no difference in trait anxiety between observer group and control group (41.25+/ 16.16 vs. 41.19+/-16.84), P>0.05. The anxiety scores of female in A and B groups were higher than that of female in control group (43.77+/-15.76, 42.93+/-15.58 vs 38.44+/-15.71), P<0.05. (3) The score of SDS in A and B group was significantly higher than that of control group (37.78+/-9.22, 39.65+/-9.87 vs 35.24+/-7.81), P<0.01. The rate of depression in observer group (11.6%, 22/190) was significantly higher than that of control group (2.6%, 5/190), Chi2=11.52, P<0.01. CONCLUSION: The allergic rhinitis may cause patients anxiety and depression, especially for female, but patients with allergic rhinitis have no significant trait anxiety. PMID- 26685398 TI - [Application of improved submental island flap in hypopharyngeal cancer reserved laryngeal function surgery]. AB - OBJECTIVE: This study aimd to evaluate the application and clinical effect of improved submental island flap in hypopharyngeal cancer reserved laryngeal function surgery. METHOD: A retrospective review of clinical data was performed on 38 patients of hypopharyngeal cancer reserved laryngeal function using sumental island flaps, by the way of improving in design of vascular pedicle, reconstructive mode of laryngeal and hypopharyngeal function and closing of wound of neck following hypopharyngeal cancer resection. Meanwhile, the effect and prognosis was comprehensively assessed on patients with hypopharyngeal cancer reserved laryngeal function using improved submental island flaps. RESULT: The submental flaps kept alive in all 38 cases. During the follow-up period, 18 cases were dead, and of them, 7 cases died of the second primary carcinoma, included 4 cases of esophagus cancer, 1 case of cancer of soft palate, 2 cases of nasopharyngeal carcinoma; and 5 cases died of cervical or parapharyngeal lymph nodes recurrence; 2 cases died of hepatic metastasis; and 4 cases died of pulmonary metastasis. The overall 5-years survival rate was 52.6%. CONCLUSION: Improved submental island flap repairing postoperative defect of hypopharyngeal cancer reserved laryngeal function has many advantages including higher success rate, more security, easy and simple to operate as well as good clinical effects, and is worth to widespread using. PMID- 26685397 TI - [Clinical efficacy of nasal cellulose powder for the treatment of allergic rhinitis]. AB - OBJECTIVE: To investigate the clinical efficacy of nasal cellulose powder for the treatment of allergic rhinitis. METHOD: Thirty-six cases of patients with allergic rhinitis were randomly divided into control group and experimental group, 18 cases in each group. The control group was treated with physiological sea water and the experimental group with nasal fibrous powder. In 14, 28 days after drug evaluation in patients objective and subjective symptoms and signs improved nasal function (nasal airway resistance, the sense of smell) was compared. RESULT: The experimental group and the control group of subjective symptoms and objective nasal function were improved, but the experimental group was significantly higher than that of control group, the difference was statistically significant (P<0.05); Two groups of patients had no adverse reaction occurred. CONCLUSION: The clinical curative effect of Nasal cellulose powder used in the treatment of allergic rhinitis is distinct, without adverse reactions, and is conducive to improving patient stuffy nose, nasal itching, sneezing and other symptoms and improve the patients quality of life, is worth clinical use. PMID- 26685399 TI - [The effect of catalase on smoking related laryngeal squamous cell carcinoma]. AB - OBJECTIVE: Investigate the effect of oxidative stress on the occurrence and development of laryngeal squamous cell carcinoma associated with smoking, and the clinical diagnostic value of catalase on smoking related laryngeal squamous cell carcinoma. METHOD: Collecting 119 smokers(including the smoking related laryngeal cancer group 68 cases, the control group 51 cases), the indexes of catalase (CAT), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH), nitric oxide (NO) in blood plasma and cancerous tissue in two groups were compared. The association between these oxidative stress indicators and the occurrence and severity of smoking related laryngeal squamous cell carcinoma was analysised by SPSS 17.0. RESULT: (1) Compared with control group, the smoke frequency and amount, CAT, MDA, GSH increased significantly in the smoking related laryngeal cancer group (P = 0.000; 0.000; 0.000; 0.000; 0.000); whereas SOD, NO decreased (P = 0.000; 0.000). (2) The lower the differentiation degree, the higher the serum CAT (P = 0.000) and the higher CAT, MDA, GSH of larynx tissue (P = 0.000; 0.000; 0.000), but the lower the serum NO (P = 0.000) and the lower SOD, NO of larynx tissue (P = 0.000; 0.000); The higher the clinical stage, the higher CAT of serum and larynx tissue and the higher GSH of larynx tissue (P = 0.000; 0.001), the lower NO of larynx tissue (P = 0.009). (3) The serum CAT, MDA were independent risk factors of smoking related laryngeal squamous cell carcinoma (OR = 1.060, 2.475; P < 0.01, P < 0.05). CONCLUSION: Oxidative stress is the key factor of the occurrence of smoking related laryngeal squamous cell carcinoma, and the CAT can be used as the indicator of clinical diagnosis of smoking related laryngeal squamous cell carcinoma. PMID- 26685400 TI - [Expression and role of IL-33 and its receptor ST2 in eosinophilic and non eosinophilic chronic rhinosinusitis with nasal polyps]. AB - OBJECTIVE: To investigate the expression and role of Interleukin-33 (IL-33) and ST2 in the nasal polyps of human Eosinophilic and non-Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS and non-ECRS). METHOD: IL-33 and ST2 protein expression in nasal polyps of ECRS and non-ECRS as well as in seemingly normal mucosa of the inferior turbinate tissue was investigated by immunohistochemical staining and messenger RNA (mRNA) expression of IL-33 and ST2 was assessed by realtime polymerase chain reaction (PCR) in 27 subjects with ECRS, 33 subjects with non-ECRS, and 11 control subjects. RESULT: (1) The ST2 was found both in nasal polyps of ECRS and non-ECRS,especially in ECRS, yet hardly found in the normal mucosa of the inferior turbinate tissue; (2) The expression of ST2 mRNA in nasal polyps of ECRS was higher than that in non-ECRS and normal inferior turbinate tissue, and the difference was both prominent in statistics (P<0.01); (3) The expression patterns of IL-33 at both mRNA and protein levels were not significantly different among the three groups (P>0.05). CONCLUSION: The IL-33 and its receptor ST2 were both expressed in human nasal polyps including ECRS and non-ECRS, meanwhile the expression patterns of ST2 at both mRNA and protein levels were significantly higher in nasal polyps of ECRS. The current study suggests that IL-33 and its receptor ST2 may play important roles in the pathogenesis of chronic rhinosinusitis with nasal polyps, especially in ECRS through the increased expression of ST2 in Eosinophils as a hypothesis. PMID- 26685401 TI - [The study of preserving the great auricular nerve in the parotidectomy]. AB - OBJECTIVE: To assess the effect for local sensory to preserve great auricular nerve in the parotidectomy. METHOD: It was a prospective study. Eighy-one patients who underwent parotidectomy were randomly divided into 2 groups, preserving the great auricular nerve group and no preserving the great auricular nerve group. They were tested with the subjective and objective sensory function testing in 3, 6, 9, 12 months after operation. We assessed the result. RESULT: In the subjective sensory function testing, the result of the preserving the great auricular nerve group was better than no preserving the great auricular nerve group. In the objective sensory function testing, the result of the preserving the great auricular nerve group was obviously better than no preserving the great auricular nerve group. There was significant difference between the 2 groups (P<0.05). CONCLUSION: It was effective for recovering the sensory function that we preserved the great auricular nerve in the parotidectomy. PMID- 26685402 TI - [Clinical, significance of the nomenclature for nasal septum tail: A preliminary study]. AB - OBJECTIVE: To observe and summarize the abnormal morphological appearance of nasal septum tail during adenoidectomies, and to have a preliminary study on its clinical significance. METHOD: One hundred and eighty-three children were shown with abnormality on nasal septum tail in 2892 cases with adenoid hypertrophy who received adenoidectomies in our department. RESULT: The abnormalities of nasal septum tail can be classified into two types: del tails and columnar ones. All children suffered from nasal septum tail received radiofrequency ablation and all had a good postoperative recovery. CONCLUSION: The presence of these two types of nasal septum tail may be related to adenoid hypertrophy, adenoiditis, sinusitis, and some congenital malformations. PMID- 26685403 TI - [A retrospective study on deep lobe tumor parotidectomy with preservation of the superficial lobe]. AB - OBJECTIVE: To study our experiences on deep lobe tumor parotidectomy with preservation of the superficial lobe of the parotid gland. METHOD: Eleven cases of benign tumor in the deep lobe of the parotid gland were analyzed restrospectively. Tumour recurrence, Frey's syndrome, paralysis of facial nerve, salivary fistula, dry mouth and feeling around the auricular lobule were evaluated. RESULT: Numbness around the auricular lobule appeared in 2 cases and salivary fistula appeared in 1 case, transient facial paralysis in 1 case. There were no patients appeared Frey's syndrome, dry mouth, permanent facial paralysis and recurrence in the 1-3 years followed up time. CONCLUSION: Deep lobe tumor parotidectomy with preservation of the superficial lobe improves the cosmetics and the feeling around the auricular lobule, reduces the incidence rate of Frey's syndrome, facial paralysis and dry mouth. PMID- 26685404 TI - [A preliminary study on the superiority of using of coblation during the maxillary sinus operation]. AB - OBJECTIVE: Observed the using of coblation during the maxillary sinus operation, to investigate the superiority of its clinical application. METHOD: Selecting 46 patients with the maxillary sinus lesions of sinusitis, nasal polyps and nasal inverted papilloma as research objects, the control group used high speed cutting drill, the research group used coblation separately for functional endoscopic sinus surgery. Six months postoperative follow-up, observeing the subjective symptoms and objective examination. RESULT: Subjective symptoms and objective examination scores of two groups of patients improved significantly. Compared with the control group, the operation time, bleeding volume and postoperative examination time are reduced in the study group of patients. Endoscopic examinations of the study group are better than the control group. CONCLUSION: Using coblation for the maxillary sinus operation, treatment are more thorough, more minimally invasive, shorten operation time, reduce bleeding and recheck time after surgery, is worthy of clinical use. PMID- 26685405 TI - [Apoptosis and migration suppression of HN-3 human laryngeal squamous cancer cells induced by photo-activation of 9-hydroxypheophorbide-alpha]. AB - OBJECTIVE: To investigate the effect and potential mechanisms about apoptosis induction and migration suppression of photodynamic therapy with a new photosensitizer, 9-hydroxypheophorbide-alpha (9-HPbD), and diode laser on HN-3 human laryngeal squamous cancer cells. METHOD: The attached HN-3 cancer cells were photosesitized with 0.29 MUg/ml and 0.59 MUg/ml 9-HPbD for 6 h and irradiated by 664 nm diode laser for 15 min at an energy density of 2.0 J/cm for activating 9-HPbD. Wound healing assay and photographing was respectively performed immediately after laser irradiation. Photographing focusing on the same location was repeated 12 h, 24 h and 36 h after PDT and cells migration distance counted respectively. H2DCFDA staining was used to assess accumulation of reactive oxygen series (ROS) 1 h after PDT. MTT assay, Hoechst33342/PI double staining, western blotting were respectively performed to assess cellular viability, apoptosis and the expression of Enos, p-c-Jun, EGFR. RESULT: Phototoxicity and apoptosis on HN-3 cells induced by 9-HPbD-PDT was exhibited in a dose-related manner. Neither 9-HPbD alone nor laser alone was cytotoxic to HN-3 cells. Generation of ROS was initiated immediately after PDT. The apoptotic cells, marked with condensed/fragmented blue or pink nuclei, and up-regulated expression of eNOS, p-c-Jun were subsequently induced 24 h after PDT. Coupled with a down-regulated expression of EGFR, a photosensitizer dose-ralated cell migration suppression was initiated by PDT. After pretreatment of GSH or ascorbic acid, a kind of antioxidant, the efficacy of PDT-induced apoptosis and migration suppression was partially inhibited. CONCLUSION: Activation of p-c-Jun, eNOS and down-regulated expression of EGFR may respectively involve in the apoptosis induction and cell migration suppression after 9-HPbD-PDT. Generation of ROS may play an important role in the course of apoptosis induction and migration suppression of HN-3 cells initiated by 9-HPbD-PDT. PMID- 26685406 TI - [Establishment and evaluation of the SD rat allergic rhinitis model]. AB - OBJECTIVE: To investigate method established and system evaluated in the model of SD rat with AR. METHOD: To establish AR model of SD rats by ovalbumin (OVA), 20 cases of SD rats were randomly divided into two groups, namely control group (10 cases) and AR group (10 cases). AR models were sensitized and challenged by OVA. Control group were used with normal saline instead of OVA. The score of pathology and praxiology were observed when the SD rats in AR group appeared typical symptom of allergic rhinitis, and levels of IL-4, IFN-gamma, IgE in the serum were examined by ELISA. According to the behavioral score, nasal histology and content of IL-4, IFN-gamma, IgE of serum, Rat allergic rhinitis model were judged successfully established or not. RESULT: Behavioral scores were significantly increased in OVA-challenged rats compared with the control group, P<0.05. Nasal epithelial goblet cells, eosinophils and lymphocytes in nasal mucosa in the AR rats exhibited obvious increase relative to the control group. IL-4, IgE levels in the AR rat exhibited obvious increase relative to control group while INF gamma levels exhibited obvious reduction (P<0.05). CONCLUSION: The allergic rhinitis models in SD rat by OVA were successfully established. The levels of IgE, INF-gamma and IL-4 in Serum can be used as objective evaluation of animal models of allergic rhinitis established successfully or not. PMID- 26685407 TI - [The clinical applications of using elastic sleeve in postoperative of salivary gland]. PMID- 26685408 TI - [Poorly differentiated neuroendocrine carcinoma of the sinonasal cavity and nasopharynx: a clinicopathological analysis]. PMID- 26685409 TI - [Clinical analysis of retropharyngeal lymphangioma being misdiagnosed as retropharyngeal abscess in child]. PMID- 26685410 TI - [Foreign body of button cell in esophagus of children: a clinical analysis]. PMID- 26685411 TI - [One case of fungal sinusitis foreign body in nasal sinus]. AB - A young female complained repeated nasal discharge for over three months with discomfort of right cheek, and oral antibiotics had less effect. She has a history of "root canal therapy" five years before. Physical examination found purulent secretion in the right middle nasal meatus, and light tenderness in the right side of the maxillary sinus area. The CT scan of paranasal sinus shown possible fungal infection of right maxillary sinus. Finally the nasal endoscopic surgery confirmed the fungus ball of right maxillary sinus with foreign body (the root canal filling material). PMID- 26685412 TI - [Facial skin flap to repair 8 cases]. AB - To determine appropriate surgical methods and flaps to apply plastic surgery of facial defects. Several plastic methods were introduced progressively to eight cases. From simple to complex, we discussed the direct suture, relaxation suture, Z-flap, flap-footed, combined or multiple flaps, and free flap method to decrease the tension in wounds. The skin and flaps were successful in all eight cases and healed the wounds. It is important to choose appropriate surgical techniques and flaps to repair facial injuries. PMID- 26685413 TI - [One case of a pregnant femal taking realgar induceing congenital inner ear malformation]. AB - A pregnant female taken realgar because of superstition, which caused the baby congenital deafness. Auditory test indicated that bilateral auditory brainstem response (ABR) hearing threshold level was greater than 90 dB nHL and auditory steady state response (ASSR) hearing level ranging from 0.5 kHz to 4 kHz was beyond 110 dB HL. Temporal bone CT showed that bilateral cochlear and semicircular canal malformations, with internal auditory canal broadened. PMID- 26685414 TI - [The application of three-dimensional CT in diagnosis of the branchial cleft cyst and fistula]. AB - The patient complained of finding on the right side of the neck fistula with discharge nine years. In recently, fistula spills significantly increased compared with the previous. Special physical examination: Right sternocleidomastoid middle 1/3 front border is seen here in a small fistula, translucence jelly secretion were spilling out when squeezeing the fistula, no smell. Ultrasound: On the right side of the upper cervical skin to submandibular gland rear could see tubular low echo area. MRI: Visible on the right side of the neck tube signal, after the submandibular gland rear. Three-dimensional CT: Visible on the right side of the neck by skin sinus crossings as deep as the tonsillar fossa lumen containing contrast agent. Clinical diagnosis: The second branchial cleft cyst and fistula. PMID- 26685415 TI - [Children's OSAHS caused by the huge fibrolipoma in pharynx nasalis: a case report]. AB - We reported a case of children's OSAHS caused by the huge fibrolipoma in pharynx nasalis. The patient was a 10-years-old child who went to the hospital with the chief complaint of "Snoring and mouth breathing during sleep for 10 years". Imaging tests found one huge tumor in pharynx nasalis before the operation. The tumor was resected totally. The postoperative pathological diagnosis was fibrolipoma. No recurrence was noted during the follow-up visit one year postoperatively. The clinical features, diagnosis, treatment, pathology and prognosis were reviewed herein. PMID- 26685416 TI - [The review of categorization features of tone perception]. AB - Categorical perception (CP) is the unique phenomenon that gradually morphed physical feature in a stimulus continuum tends to be perceived as discrete representations. CP has been evidenced in several modalities in the sensor perception. The first study of CP of phonetic perception was performed in 1957. However, the early CP studies focused on segmental features. The first study of CP of pitch contours was performed until 1976. This article will review the results of previous studies focus on the categorical perception applies to the lexical tone perception. PMID- 26685417 TI - [Clinical diagnosis and treatment of allergic pharyngitis]. AB - Although the concept of united airway disease has been widely accepted, most scholars emphasize only the effect of rhino-sinusitis while ignoring the pharyngeal factors to the lower airway, especially to the allergic pharyngitis (AP), which still lacks enough awareness. First of all, absence of unified diagnostic standard leads to the lack of epidemiological data, which, results in doctors' personal experience but no guideline in treatments. In addition, it is still not clear that the role of AP in the allergic airway diseases and its relationship with asthma. However, the number of patients with AP has been increasing obviously in daily clinic practice. Combined with the previous observation, this paper does a systematic review about the clinical problems of AP, expecting to give a hand to the clinical diagnosis and treatment of AP. PMID- 26685418 TI - [An association between adenoid hypertrophy and exstra-gastroesophageal reflux disease]. AB - Adenoid hypertrophy is a disease that mostly occurs among children of 3-5 years old. It is caused by repeated inflammation and infection of nasopharynx and its adjoin parts, or the adenoid itself, which will finally leads to pathological hyperplasia of adenoid. With so much information we have acquired about this disease, its specific mechanism remains unknown. In recent years, some researches have indicated that adenoid hypertrophy may have something to do with extra gastroesophageal reflux, in which pepsin plays a very important role, and pepsin will do a series of pathological damages to the upper airway as it reaches the upper respiratory tract. Based on relative domestic and foreign literature, this paper attempts to make a review about the relationship between gastroesophageal reflux and adenoid hypertrophy. PMID- 26685419 TI - The clinical and economic value of flexible diagnostic panels for respiratory pathogen testing. PMID- 26685420 TI - Influenza symptoms and the role of laboratory diagnostics. PMID- 26685421 TI - PCR-based DNA enrichment enhances detection of mutations in oncology. PMID- 26685422 TI - The evolution of routine PCR testing: insights from the core lab model. PMID- 26685423 TI - Glucose or HbAlc? The answer is both. PMID- 26685424 TI - The glucose vs. HbA1c controversy. Clinicians weigh arguments for both types of diabetes testing. PMID- 26685425 TI - The White House Forum on Antibiotic Stewardship impacts labs across the U.S. PMID- 26685426 TI - What do MTs and MLTs do? Exploring the tasks of laboratorians. Two surveys reveal valuable information for clinical lab leaders. PMID- 26685428 TI - The LIS, the healthcare market, and the POL. PMID- 26685427 TI - RNA integrity numbers: an introduction. PMID- 26685429 TI - Systems-guided support to enable personalized medicine. PMID- 26685430 TI - Noninvasive prenatal screening: replacing confusion with clarity. PMID- 26685431 TI - Automated testing in hematology: the role of rules in setting a standard. PMID- 26685432 TI - Blood gas testing: a brief history and new regulatory developments. PMID- 26685435 TI - Member Profile. Brotherly Boost. PMID- 26685433 TI - Training and certification to perform urine studies. PMID- 26685436 TI - The uncertain future of the Cadillac tax. PMID- 26685437 TI - What does an MRI scan cost? AB - Historically, hospital departments have computed the costs of individual tests or procedures using the ratio of cost to charges (RCC) method, which can produce inaccurate results. To determine a more accurate cost of a test or procedure, the activity-based costing (ABC) method must be used. Accurate cost calculations will ensure reliable information about the profitability of a hospital's DRGs. PMID- 26685438 TI - Every penny counts: interest-free loan programs could benefit both hospitals and patients. AB - Patients' average deductibles have more than quadrupled, and their out-of-pocket costs are much higher now than even a decade ago. The higher a hospital bill, the less likely a patient is to pay. Zero-interest loan programs encourage patients to pay, helping both patient and hospital stay afloat. PMID- 26685439 TI - Developing a neighborhood primary care strategy. AB - For building and maintaining a primary care workforce to staff an integrated care delivery strategy, considerations include: > Geographic presence > Patient care modeling > Professional staffing. PMID- 26685440 TI - Identifying PHM market and network opportunities. AB - Two key processes for healthcare organizations seeking to assume a financially sustainable role in population health management (PHM), after laying the groundwork for the effort, are to identify potential PHM market opportunities and determine the scope of the PHM network. Key variables organizations should consider with respect to market opportunities include the patient population, the overall insurance/employer market, and available types of insurance products. Regarding the network's scope, organizations should consider both traditional strategic criteria for a viable network and at least five additional criteria: network essentiality and PHM care continuum, network adequacy, service distribution right-sizing, network growth strategy, and organizational agility. PMID- 26685441 TI - Rural hospitals: an asset in the continuum of care. AB - When embarking on a partnership or acquisition, a rural hospital and a larger health system can accomplish a smooth transition, as long as they both keep in mind: > The fundamental (and financial) differences between urban and rural hospitals > The areas where the rural hospital in the partnership or acquisition is profitable > The importance of a clinic strategy in a partnership. PMID- 26685442 TI - Should MA plans try to attract the sick? AB - Although attracting a mixture of well and sick patients provides a good risk mix for managed care plans, bringing in more high-risk enrollees may mean a higher reward for both patients and providers. Data systems and analytics have improved, allowing hospitals and health systems to better mitigate the risks associated with sicker patients. These new technologies and capabilities can enable these provider organizations to better manage care for patients who require treatment for multiple chronic conditions. PMID- 26685443 TI - Revenue risk and price transparency in hospital-based laboratories. AB - Two developments with important revenue implications for hospital laboratories demand the attention of hospital finance leaders: > Significant differences in pricing between higher-priced hospital-based laboratory services and lower-priced services delivered by commercial laboratories give patients a disincentive to use the hospital-based services. > Hospital operating revenue will be substantially affected beginning in 2017 by deep, statutory cuts in payment for the highest volume tests on the Part B Clinical Laboratory Fee Schedule. PMID- 26685444 TI - Reducing security risk using data loss prevention technology. AB - Data loss/leakage protection (DLP) technology seeks to improve data security by answering three fundamental questions: > Where are confidential data stored? > Who is accessing the information? > How are data being handled? PMID- 26685445 TI - The low risk and high return of integrative health services. AB - Supplemental treatments and practices such as yoga, acupuncture, guided imagery, and meditation can benefit not only patients in their recovery but also hospitals and health systems financially and operationally. Benefits include: > Savings in sedation costs for patients who use guided imagery during procedures > Increased revenue due to measurably increased patient satisfaction > Decreased length of stay. PMID- 26685446 TI - Why affiliate only once? PMID- 26685447 TI - Getting ahead on price transparency: a playbook for healthcare finance leaders. PMID- 26685448 TI - The future of patient engagement. PMID- 26685449 TI - Lessons from the latest Medicare ACO report card. PMID- 26685450 TI - Data storage: a new frontier for real estate outsourcing. PMID- 26685451 TI - SAFETY, TRANSPARENCY AND PHYSICIAN LEADERSHIP. PMID- 26685452 TI - HEALTH CARE TRANSPARENCY MOVEMENT GAINING GROUND. PMID- 26685453 TI - TRANSFORMING HEALTH CARE DELIVERY INTO A LEARNING HEALTH CARE SYSTEM. PMID- 26685454 TI - USING LEAN MANUFACTURING TO IMPROVE PATIENT CARE IN A RURAL UROLOGICAL PRACTICE. PMID- 26685455 TI - PHYSICIAN LEADERS' ROLES IN SUPPLY CHAIN MANAGEMENT. PMID- 26685456 TI - HEALTH CARE'S SUPPLY CHAIN: ISSUES TO CONSIDER. PMID- 26685457 TI - IMPROVING APPENDECTOMY OUTCOMES USING ADVANCED ANALYTICS AND TEAM STRUCTURES. PMID- 26685458 TI - CLINICAL INFORMATICS: NEW BOARD CERTIFICATION AND FELLOWSHIP FOR PHYSICIAN LEADERS. PMID- 26685459 TI - 340B: MAJOR CHANGES MAY BE COMING TO THE FEDERAL DRUG DISCOUNT PROGRAM FOR LOW INCOME AND VULNERABLE POPULATIONS. PMID- 26685460 TI - LEADING CHANGE: WHAT IS BEING ASKED OF PHYSICIAN LEADERS? PMID- 26685461 TI - CONGRATULATIONS, NEW PHYSICIAN LEADER... YOU'RE NO LONGER SPECIAL. PMID- 26685462 TI - INTEGRATING BUSINESS EDUCATION IN MEDICAL SCHOOLS: A MULTICENTER SURVEY. PMID- 26685463 TI - ENGAGING PHYSICIANS IN CLEAR DOCUMENTATION: A PATHWAY TO VALUE. PMID- 26685464 TI - CREATING YOUR PERSONAL LEADERSHIP PHILOSOPHY. PMID- 26685465 TI - THE ANATOMY OF A MENTOR-MENTEE RELATIONSHIP. PMID- 26685466 TI - VIOLENCE AGAINST NURSES: THE ULTIMATE BETRAYAL. PMID- 26685467 TI - IN MEMORIAM: PAULETTE GAIL BURNS, PH.D., RN 1949-2014. PMID- 26685468 TI - View from the North End: a model for future dental schools? PMID- 26685469 TI - Intercollegiate Advisory Committee for Sedation in Dentistry: Review of the Guidelines Published in April 2015. AB - This review article considers the development of the Intercollegiate Advisory Committee for Sedation in Dentistry (IACSD) guideline produced by the four dental faculties of the Royal Colleges and the Royal College of Anaesthetists for conscious sedation use in dentistry. An outline of the scope of the document, which aims to set definitive standards for conscious sedation provision within the dental environment, is given. The IACSD guideline sets a national standard for all aspects of dental conscious sedation provision, from training of the team, environment requirements and clinical delivery; it is therefore a requirement that all dentists, doctors and healthcare professionals providing, or supporting, dental conscious sedation are aware of the content. CPD/Clinical Relevance: This article should help with the understanding of the development background, scope of the guideline and relevance to the dental practice of dental conscious sedation. PMID- 26685470 TI - Modern Endodontic Planning Part 2: Access and Strategy. AB - Poor access and iatrogenic damage can result in failed root canal treatment. Understanding tooth anatomy improves access and ensures that the clinician is cleaning and shaping the whole root canal system. If a canal is missed treatment usually fails. This paper revisits tooth anatomy and discusses how to ensure that access is optimized, but not at the expense of precious tooth structure. The concept of multi-visit root canal treatment is also addressed with emphasis on the, often overlooked, aspect of temporization. CPD/Clinical Relevance: Good anatomical knowledge of teeth is the cornerstone of endodontics. Once root treatment has begun the clinician must be logical about how many visits to take and how to temporize teeth between such visits. PMID- 26685471 TI - Class II Resin Composites: Restorative Options. AB - Tooth-coloured, resin composite restorations are amongst the most frequently prescribed forms of dental restoration to manage defects in posterior teeth. The attainment of a desirable outcome when placing posterior resin composite restorations requires the clinician to have a good understanding of the benefits (as well as the limitations) posed by this material, together with a sound knowledge of placement technique. Numerous protocols and materials have evolved to assist the dental operator with this type of demanding posterior restoration. With the use of case examples, four techniques available are reported here. CPD/Clinical Relevance: This article explores varying techniques for the restoration of Class II cavities using resin composite. PMID- 26685472 TI - Case Report: Beware the Silver Nitrate Stick--A Risk Factor for Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ). AB - Topical silver nitrate may be used in oral and maxillofacial clinical settings owing to its astringent, caustic and disinfectant properties. Uses of the toughened silver nitrate pencil stick include haemostasis at bleeding points and for the management of aphthous ulcers, hypergranulation tissue, warts and verrucas. We present an interesting case of apparent silver nitrate-induced, bisphosphonate-related osteonecrosis of the hard palate following mucosal lesion biopsy in a multiple myeloma patient receiving zoledronic acid intravenous infusions. Our review of the literature indicates that this is the first report of such a scenario. CPD/Clinical Relevance: Clinicians must consider all potential sources of chemical and mechanical trauma to the bone and overlying mucosa when managing patients at risk of developing bisphosphonate-related osteonecrosis of the jaw. PMID- 26685473 TI - Pain Part 5a: Chronic (Neuropathic) Orofacial Pain. AB - Neuropathic pain is a significant social and economic burden. Back pain, joint pain and headaches affect over 30% of the population. Chronic orofacial pain is a common condition and is difficult to diagnose and manage. This two-part paper aims to provide an overview of novel understanding of neuropathic pain, and furnish clinical teams with an update on the less common and less well-recognized chronic orofacial conditions. Headaches and temporomandibular disorders are the most common conditions and are covered in separate papers (6 and 10). Trigeminal neuralgia, burning mouth, and trigeminal autonomic cephalgias are also covered in separate papers (7, 8 and 9). The remaining conditions: post-traumatic neuropathy (nerve injury); and persistent idiopathic facial pain and atypical odontalgia are discussed in this and the following paper. Clinical Relevance: Neuropathic pain, though rare, is a consequence of dental treatment. Nerve injury in relation to M3M surgery, dental implants, endodontics and local anaesthesia result in 70% of affected patients experiencing chronic neuropathic pain. PMID- 26685474 TI - Minimizing Digital Data Loss. AB - Clinical photography has now reached all areas of dentistry, with camera equipment and photography skills being present in many practices. Whilst taking good photographs is just one part of improving record-keeping, the other part, which is arguably the more, important aspect, is to store securely this vast amount of data that is created. This article intends to explore the options available to practices to store the data securely and recommends the easiest and most effective ways available today. CPD/Clinical Relevance: With clinical photographs becoming ever more important in the field of dentistry, correct storage and use of camera equipment is important. PMID- 26685475 TI - Mouth Cancer for Clinicians Part 5: Risk Factors (Other). AB - A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team an overview of other cancer risk factors agents, such as human papilloma viruses (HPV) and irradiation. PMID- 26685476 TI - Ectodermal Dysplasia: A Clinical Overview for the Dental Practitioner. AB - The term ectodermal dysplasia (ED) is used to describe a group of rare congenital disorders characterized by abnormalities of two or more ectodermal structures such as the skin, hair, nails, teeth and sweat glands. This paper will give an overview of the aetiology of ED and describe the manifestations and dental management of this condition. In particular, the important role of the dental practitioner in the identification and management of patients with ED will be highlighted. CPD/Clinical Relevance: Dental practitioners should be aware of the oral features of ectodermal dysplasia and be able to make timely referrals and provide appropriate continuing care for these patients. PMID- 26685478 TI - Technique Tips--Finding the Ideal Surface Disinfectant. PMID- 26685477 TI - Clinical Challenges Q&A 14. Facial Paralysis. PMID- 26685479 TI - [Retinal Cell Biology and Molecular Targeting Therapy--Post-VEGF Era for Innovative Drug Development]. PMID- 26685480 TI - [Adrenomedullin-Receptor Activity-modifying Protein 2 (RAMP2) System in Retinal Angiogenesis]. AB - Adrenomedullin (ADM) was originally identified as an endogenous peptide having vasodilating functions. Following that, ADM has been shown to possess pleiotropic functions including angiogenic potency. The vascular function of ADM is mainly regulated by a receptor activity-modifying protein 2 (RAMP2). However, pathophysiological roles of ADM-RAMP2 system in retinal angiogenesis remain to be clarified. We analyzed (1) a oxygen-induced retinopathy (OIR) model using heterozygous ADM and RAMP2 knockout mice (ADMJ+/- and RAMP2+/-, respectively), (2) proliferation and migration of retinal endothelial cells in vitro, (3) retinal angiogenesis during developmental stage using drug-inducible endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-), and (4) an OIR model treated with intravitreal injection of anti-ADM antibody. We found that ADM mRNA expression was upregulated under hypoxic conditions in OIR model. In ADM+/-, pathological neovascularization as well as VEGF and eNOS mRNA expression was suppressed. In addition, proliferation and migration effects of ADM on retinal endothelial cells were confirmed in vitro. We found that ADM-RAMP2 system also plays important roles in retinal vascular development, and Notch signaling is possibly involved. Finally, we revealed that intravitreal injection of anti-ADM antibody reduced pathological retinal angiogenesis in OIR model. From these results, we clarified that ADM-RAMP2 system plays important roles in both the pathological and physiological retinal angiogenesis. ADM-RAMP2 system is a hopeful new therapeutic method for controlling pathological retinal angiogenesis in ocular diseases. PMID- 26685481 TI - [Periostin in the Pathogenesis of Proliferative Vitreoretinopathy]. AB - Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery. The hallmark of PVR is the formation of subretinal and epiretinal fibrotic membranes that can lead to traction retinal detachment due to their contractile properties. Surgical removal of the fibrotic membranes and retinal detachment repair are the first choice treatments for PVR. Despite recent progress in surgical techniques, recurrent detachment can lead to irreversible damage and a poor prognosis for visual acuity. Therefore, it is important to develop new molecular targeting therapies based on the exact pathogenesis of PVR. In order to determine the genes responsible for development of PVR, we performed gene expression profiling of fibrous membranes excised from PVR patients using DNA microarray analysis. This analysis revealed significant up regulation of periostin. We also found increased periostin expression in the vitreous and retinal pigment epithelial (RPE) cells in fibrous membranes of PVR patients. In vitro, periostin increased proliferation, adhesion, migration and collagen production in primary human RPE cells through integrin alphaV-mediated FAK and AKT phosphorylation. Blockade of periostin suppressed migration and adhesion induced by TGF-beta2 and PVR vitreous. In vivo, periostin inhibition had the inhibitory effect on progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells. These results identified the novel causal link between periostin and the generation of PVR membranes as well as a promising therapeutic target for PVR. PMID- 26685482 TI - [The Evidence for the Treatment of Polypoidal Choroidal Vasculopathy]. AB - The optimal treatment of polypoidal choroidal vasculopathy (PCV) is still undetermined. Photodynamic therapy (PDT) is effective for PCV but the Treatment effect declines after one year. While some reports show the efficacy of anti vascular endothelial growth factor (VEGF) therapy for PCV, other reports show treatment-refractory cases. In this article, the author reviews the results of our multicenter randomized trial, conducted to compare the efficacy of PDT and ranibizumab in PCV patients. The results showed that ranibizumab is more effective in visual gain in two-year follow up. Central retinal thickness improved with both treatments and there was no difference between them. Our results provide evidence that ranibizumab is superior to PDT monotherapy for treatment of PCV in terms of visual acuity. PMID- 26685483 TI - [Atp6ap2/ (Pro) renin Receptor is Required for Laminar Formation during Retinal Development in Mice]. AB - (Pro) renin receptor [(P) RR], a key molecule for tissue renin-angiotensin system, was originally identified as Atp6ap2, an accessory subunit for vacuolar H(+)-ATPase that is a multi-subunit proton pump involved in fundamental cellular physiology. In this study, to elucidate the physiological functions of Atp6ap2/ (P) RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P) RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/ (P) RR did not affect retinal cell differentiation, but led to laminar disorganization in the photoreceptor layer with dysfunction of photoreceptors. Cell adhesion and polarity molecules, all of which were co-localized with Atp6ap2 at the apical edge of the developing retina, were dispersed together with mislocalization of retinal progenitors apart from the apical surface in Atp6ap2 conditional knockout mice. Among these molecules, co-immunoprecipitation using retinal homogenates and Atp6ap2/(P) RR-transfected cells showed that Atp6ap2/(P) RR interacted with partitioning defective 3 homolog (Par3) protein, known to play a pivotal role in planar cell polarity in the Par-atypical protein kinase C system. Atp6ap2 interacted with Par3 protein that plays a pivotal role in planar cell polarity. Our data provide a novel function of Atp6ap2 required as a cell polarity determinant for retinal laminar formation. PMID- 26685484 TI - [Proof of a Concept for Bioengineered Organ Replacement to Restore Lacrimal Gland Function]. AB - The lacrimal gland has an essential role in maintaining a homeostatic environment for a healthy ocular surface by tear secretion. Dry-eye disease, caused by lacrimal gland dysfunction, is a prevalent eye disease that results in corneal epithelial damage. Regenerative medicine, such as stem cell therapy, is expected to be a promising approach to restore the lacrimal gland function. Recently, a novel strategy has been reported of developing a fully functioning bioengineered organ by engraftment of a bioengineered organ germ generated via 3-dimensional cell manipulation using immature stem cells in vitro. We demonstrated an orthotopic transplantation of the bioengineered lacrimal gland germ into adult mice, in which the extra-orbital lacrimal gland has been removed. This mouse model mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germ and harderian gland germ both developed in vivo; they achieved physiological functionality, including tear secretion in response to nervous stimulation and ocular surface protection. This study provided novel evidence for the successful replacement of a fully functional lacrimal gland via engraftment of a bioengineered germ. PMID- 26685485 TI - [Evaluation of Diabetic Retinopathy with Ultra-wide Field Fluorescein Angiography]. AB - PURPOSE: The ultra-wide field scanning laser ophthalmoscope (Optos 200Tx, Optos, Scotland, UK) provides retinal images of 200 degrees in a single capture which covers more than 80% of the retina. Fluorescein angiography with Optos 200Tx is useful to visualize the microcirculations of peripheral retina. It allows to evaluate peripheral pathology more precisely than conventional fundus photography. The purpose of this study was to evaluate the fluorescein angiography findings of eyes in diabetic retinopathy patients by using ultra-wide field fluoresrein angiography. SUBJECTS AND METHODS: Ultra-wide field fluoresrein angiography was performed on 154 eyes of 77 patients with diabetic retinopathy. We divided the fundus into three zones, the posterior pole, the mid-periphery and the far-periphery. Capillary non-perfusion areas and retinal neovascularization in each zone were evaluated. RESULTS: One hundred thirty eyes (84%) exhibited capillary non-perfusion areas. Ten eyes (7.7%) were found to have a capillary non perfusion area only in the far-periphery. Seventy two eyes (47%) exhibited retinal neovascularization. Retinal neovascularization was observed most in the mid-periphery (58 eyes; 81%); 8 eyes (11%) were found to have retinal neovascularization in the far-periphery. CONCLUSION: Ultra-wide field fluorescein angiography revealed the microcirculatory disturbance in the peripheral retina of diabetic patients not evident by conventional fundus photography and it was useful for evaluating the status of the diabetic retinopathy. PMID- 26685486 TI - [Side Effects of Low Dose Atropine]. AB - PURPOSE: Because highmyopia causes severe visual impairment, it is important to prevent the progression of myopia. Recently, the prevention of myopia progression by low dose atropine was reported from Singapore. We started the study of low dose atropine in Japanese children, with the aim of investigating the side effects of low dose atropine. SUBJECT AND METHODS: The participants were 16 children between the age of 6 and 12. They receive 0.01% atropine once nightly in both eyes. Refractive error, distant vision, near vision, accommodation and pupil diameter were checked before (baseline) and two weeks after the treatment (second baseline). Also, we checked subjective symptoms and adverse events. RESULTS: There was no significant change between baseline and second baseline in the refractive error, distant vision, near vision. Accommodation decreased mean 1.5 D (p < 0.01) and the pupil diameter was mean 0.7 mm larger (p < 0.0001), but the subjective symptoms were minimal. Accommodation and pupil diameter showed significant changes. Severe subjective symptoms and adverse events were not found in any of the cases. CONCLUSION: The side effects of low dose atropine were not severe. The treatment could be continued for the prevention of myopia. PMID- 26685487 TI - [Why macrolides?]. PMID- 26685488 TI - Some of the Best Sermons are Lived, Not Preached! PMID- 26685489 TI - New England Compounding Center Indictment. AB - This article is a review of the lapses in compliance with United States Pharmacopeia standards and pharmacy law as alleged by the New England Compounding Center indictment. This indictment was a result of an outbreak of fungal meningitis traced to fungal contamination of compounded methylprednisolone suspension for epidural steroid injections. This article is also intended as a gap analysis for compounders to review compliance at their own facility, and, if necessary, take the appropriate steps to implement best practices. PMID- 26685490 TI - Standing Together Fixing the Drug Quality and Security Act. PMID- 26685491 TI - STANDARDIZED COMPOUNDING: The Importance of Doing it the Same Way Every Time. AB - ABSTRACT compounding within a pharmacy, which is an integral part of quality management. A pharmacy that has not established standardized compounding procedures, which are important to ensuring that all preparations are of high quality, has created an environment within which errors will occur. The same applies to a pharmacy that has established standardized compounding procedures but employs pharmacists who do not have a common understanding of the standard operating procedures within their pharmacy. PMID- 26685492 TI - Bedside Manner: NOT JUST FOR DOCTORS ANYMORE. AB - Pharmacists play a unique role in health care, one that is integral for proper communication and exchange of information among prescribers and patients. This relationship is referred to as the Triad Relationship within this article. The success of the Triad Relationship is largely based on the pharmacist's ability to adapt and effectively tailor lines of communication, reinforce validity behind information and recommendations, maintain privacy, and establish reputation based on trust. Word spreads quickly in the healthcare community; those pharmacists that reach to achieve and maintain Triad Relationships help to ensure that pharmacists will continue to remain among the most trusted professionals. PMID- 26685493 TI - Quality Assurance and Quality Control, Part 1. AB - The tragedy surrounding the New England Compounding Center and contaminated steroid syringe preparations clearly points out what can happen if quality assurance and quality-control procedures are not strictly practiced in the compounding of sterile preparations. This article represents part 1 of a 2-part article on quality-assurance and quality-control procedures and serves as an introduction to the topic of finished preparation release checks and tests. Part 1 highlights what is required to comply with United States Pharmacopeia General Chapter <797>, and part 2 continues with a discussion on the requirements of <797> as well as what is required in chapter < 1163> with respect to quality assurance of compounded sterile preparations. Written procedures, good documentation practices, and specific details for clarity, sterility, and bacterial endotoxin (pyrogen) testing are presented in this article. PMID- 26685494 TI - BASICS OF STERILE COMPOUNDING: Sterilization Methods in Sterile Product Manufacturing. AB - Sterilization methods to produce sterile preparations include heat, gas, radiation, and filtration. This article focuses on heat, gas, and radiation sterilization, plus a brief introduction to bright-light sterilization. Microbiology basics and microbial death kinetics, key to understanding why these sterilization methods work, will also be briefly discussed. Filtration sterilization will be covered in a separate article. PMID- 26685495 TI - Transdermal Delivery of Nisoldipine: Refinement of Vehicles. AB - Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine. PMID- 26685496 TI - Skin Permeation and Antinociception of Compounded Topical Cyclobenzaprine Hydrochloride Formulations. AB - Cyclobenzaprine has been commonly compounded by pharmacists into topically applied dosage forms for the treatment of pain disorders. However, the efficacy and transdermal penetration of topically applied compounded cyclobenzaprine is currently unknown. In this study, the transdermal penetration of cyclobenzaprine was studied in Franz diffusion cells using porcine skin. Cyclobenzaprine was compounded in two commercially available bases; Lipobase, Lipoderm, and a standard poloxamer lecithin organogel. In addition, cyclobenzaprine was tested in an in vivo formalin pain model. Cyclobenzaprine 5% compounded into all three bases yielded significant transdermal penetration and results in modest levels of cyclobenzaprine being retained in the skin tissue. Systemically administered cyclobenzaprine (10 mcg/kg), but not topically administered cyclobenzaprine (1% and 5%), attenuated nociception in a rodent formalin pain model. PMID- 26685497 TI - Analgesic Efficacy and Transdermal Penetration of Topical Gabapentin Creams: Finding an Optimal Dose and Pre-treatment Time. AB - Many patients with chronic neuropathic pain continue to suffer despite traditional pharmacotherapy. As a result, pharmacists commonly compound gabapentin into creams, gels, and ointments as an alternative treatment option. In this study, various concentrations (1%, 5%, and 10%) of topical gabapentin compounded in Lipoderm were applied at various pre-treatment times (30 minutes, 1 hour, and 4 hours) to investigate what gabapentin concentration and pre-treatment time best attenuates formalin-induced nociceptive behaviors in a rodent model. A 30-minute pre-treatment with 5% gabapentin demonstrated maximum attenuation of nociceptive behaviors in this in vivo preclinical pain model. Nociceptive behaviors unexpectedly increased when gabapentin concentration or pre-treatment time was increased, suggesting both antinociceptive and pronociceptive effects of transdermal gabapentin administration. Gabapentin permeation into the skin and deeper tissues of the hindpaw was measured following the in vivo study. Skin and deep tissue permeation of gabapentin was both dose and time-dependent. Maximum deep-tissue permeation occurred within 30 minutes of topical application. Skin concentrations increased with a longer 1-hour pre-treatment. Minimal skin and deeper tissue levels were found following a 4-hour pre-treatment. These results suggest that topical gabapentin may be antinociceptive in a rodent formalin model at specific doses and pre-treatment intervals. PMID- 26685498 TI - Declining Experimental Skills Among Physiologists. PMID- 26685499 TI - Mobile Phone Radiation: Physiological & Pathophysiologcal Considerations. AB - It is documented that electromagnetic emissions from mobile phones can interfere with brain's signal processing activity due to their oscillatory similitude to the inherent rhythms of the brain, akin to "electromagnetic interference" observed while using mobile phones in aeroplanes. At high power density levels, thermal effects occur, some of which can be attributed to heat induced stress mechanisms. The less understood non-thermal effects occur at low radio frequency/microwave power density levels and are not accompanied by any body temperature rise. The safety standards set by international agencies are based on thermal effects. For the mobile phones, ICNIRP 1998 guidelines restrict spatial peak of microwave exposure to 2 W/Kg SAR values averaged over 10 g of tissue for 6 minutes. Some of the reported electromagnetic radiation (EMR) induced adverse effects are brain tumours, male infertility and immune dysfunction with increased susceptibility to infections. Pathophysiological mechanisms of interaction of EMR at plasma membrane are calcium efflux from cell membranes, increased expression of stress proteins, influence on channels/gap junctions in cell membrane, overproduction of reactive oxygen species, ornithine decarboxylase activation, reduction in melatonin levels, decrease in protein kinase C activity, damage to DNA and change in gene expression in brain cells and altered blood-brain barrier. There are equal number of conflicting reports in literature regarding EMR exposure and brain tumours. A comprehensive review concludes "overall the studies published to date do not demonstrate an increased risk within approximately 10 years of use for any tumour of the brain or any other head tumour." Another review summarises that there is "enough data to convince that long-term exposure to low intensity EMR below the ICNIRP guidelines can promote cancer development". However the time limit for exposure has been suggested as more than 10 years. For conducting epidemiological studies, some of the difficulties experienced are obtaining unexposed controls or cohorts, follow up of the cohorts, actual dose measurement for exposure assessment in case-control studies, inaccuracy, recall bias and selective non response in recall of phone use by mobile phone users, long induction times, long latencies (the effects we observe now are of analogue phones that are no longer used ) and the rarity of observed malignancies, variable ways of using the phone by the user i.e. left or right ear, head sets/speaker/blue tooth etc. Large-scale epidemiological studies should employ personal MW dosimeters for strict dose measurement and for interpreting actual tissue exposure. PMID- 26685500 TI - Sex Difference in the Effect of Whole Body Heating on Cardiovascular Functions. AB - Cold pressor test (CPT) is a well-known method for evaluating non-baroreflex mediated autonomic cardiovascular functions in humans. It has been reported that autonomic cardiovascular response to CPT differs in males and females and that heat stress attenuates the increase in arterial blood pressure during CPT. Study has also indicated that heat stress attenuates the increase in arterial blood pressure during CPT. The present study assessed the autonomic cardiovascular reactivity in males and females during cold pressor test before and after whole body heating for 40 min. 20 healthy Indian males and 18 females participated in the study. The participants were exposed to 40 degrees C dry bulb temperature and 40% relative humidity in a simulated thermal chamber. They performed CPT before and after heat stress and their beat to beat heart rate and blood pressure were recorded. It was observed that baroreflex sensitivity (BRS) was significantly lower in females during CPT before heat stress (p < 0.01) as well as after heat stress (p < 0.01). Moreover, following whole body heating, the BRS during CPT increased slightly in females but not in males. Stroke Volume (SV) increased significantly during CPT before heat stress in females from pre-heat baseline (82 ml/beat vs. 101 ml/beat) (p < 0.001) as well as during CPT after heat stress from post-heat baseline (75 ml/beat vs. 95 ml/ beat) (p < 0.01). SV increased significantly in males during CPT after heat stress only (p < 0.01) as compared to post-heat baseline (82.5 ml/beat vs. 94.5 ml/beat). Frequency domain analysis of heart rate variability indicated that during CPT, low frequency power in males was higher than females (p < 0.05) and high frequency power was higher in females than males (p < 0.05). This suggests that autonomic modulation of cardiovascular function during CPT in males is mediated mainly via sympathetic neural system and in females it is mediated via vagal system. LF/HF ratio during CPT was found to be significantly higher in males (2.54) than females (1.27) before heat stress (p < 0.01). PMID- 26685501 TI - Assessment of Cardiovascular Autonomic Functions and Baroreceptor Reactivity in Women with Premenstrual Syndrome. AB - OBJECTIVES: The study was conducted to assess the autonomic status of women with mild PMS using short-term heart rate variability (HRV) analysis and conventional autonomic function tests (CAFT). METHODS: Sixty females in the age group 17-25 years with mild premenstrual syndrome were identified using a self-report questionnaire, the shortened premenstrual assessment form. HRV and CAFTs were recorded 1- 5 days prior and 8-10 days after menstruation. RESULTS: The subjects showed a significant increase in HR and SBP in luteal phase. In HRV, an increase in mean HR and LF-HF ratio were seen in the luteal phase whereas an increase in the NN50, RMSSD and pNN50, HF, HF(nu) and TP were seen in the follicular phase. In CAFT, no change in HRB, 30:15 and El I ratios but increase in ?DBP(ihg) in the luteal phase was seen. CONCLUSION: The increase in HR and SBP in the luteal phase could be because increased water and salt retention due to the ovarian steroids. A decrease in HRV, increase in ?DBPihg with no change in 30:15 ratio in the luteal phase could be attributed to delayed withdrawal of ovarian hormones in the luteal phase. PMID- 26685502 TI - Cardiovascular Autonomic Neuropathy in Systemic Lupus Erythematosus. AB - PURPOSE: Objective is to evaluate cardiovascular autonomic function in SLE by simple non-invasive tests. METHODS: A case control study was carried out involving 18-50 yrs old previously diagnosed SLE patients and same number of age and sex-matched controls. Parasympathetic function was assessed by heart rate (HR) response to Valsalva maneuver, deep breathing and standing. Sympathetic function was evaluated by blood pressure response to standing and sustained hand grip test (HGT). RESULTS: There were 50 female SLE patients. They had significantly higher minimum resting HR and diastolic blood pressure (DBP). HR variation with deep breathing, expiratory inspiratory ratio, 30:15 ratio and DBP change in response to HGT were significantly lower inpatients compared to controls. Thirty patients (60%) had at least one abnormal or two borderline test results indicating autonomic impairment of which 27 had parasympathetic dysfunction and 7 had sympathetic dysfunction. CONCLUSION: Autonomic dysfunction is common in SLE with higher prevalence of parasympathetic impairment. PMID- 26685503 TI - Effect of Moderate Aerobic Exercise Training on Autonomic Functions and its Correlation with the Antioxidant Status. AB - Aerobic exercise is a proven measure to enhance the cardio-respiratory efficiency. This improvement isprimarily due to improvement in autonomic function where in there is increase in the parasympathetic function and decrease in sympathetic function. Exercise also affects many metabolic activities in our body and may be one of the factors which reduce the oxidative stress. The aim of the present study was to see the effect of moderate aerobic exercise training on autonomic function and its correlation with antioxidant status. 30 healthy volunteers in the age group of 18-22 years were screened. Autonomic function tests included activity (tone) and reactivity parameters. Antioxidant status was assessed by the level of malondialdehyde in plasma. We observed a significant change in SBP, DBP, LF nu, HF nu, delta value of DBP in CPT and MDA. Our findings are consistent with earlier findings that short duration physical training is known to reduce blood pressure and that there is a relationship between HF (in HRV) and training response Physical exercise also provides a favorable change in the biochemical parameters such as MDA. PMID- 26685504 TI - Gender Difference in Fatigue Index and its Related Physiology. AB - Fatigue index exhibits gender difference. This study was carried out to compare fatigue index of young, national level male and female field hockey players; and to explore physiological variables contributing to this difference. We measured running-based anaerobic sprint fatigue index and selected physiological parameters in male and female players matched for age, duration of training, diet, habitual physical activity, body weight and BMI. The male hockey players showed lower resistance to repeated sprints fatigue than the female players. Body weight, BMI and power variables positively correlated to fatigue index in both sexes; while lean body mass and age in males only, and body fat % in females only were found to be correlated to fatigue index. Difference in lean body mass, body fat %, strength and anaerobic power might be responsible for gender difference in intermittent & repeated sprints fatigue index observed in studied players. PMID- 26685505 TI - Involvement of Neuropeptide Orexin B in Basolateral Amygdala Mediated Consummatory Behaviour in Male Wistar Albino Rats. AB - The basolateral amygdala has been implicated in the regulation of food intake besides the hypothalamic centres. In the present study, we hypothesized that the Orexin B, a polypeptide identified in the lateral hypothalamic region, may be involved in the modification of the functions the of amygdaloid centres. We therefore studied the effect of infusion of Orexin B and its antagonist (TCS-OX2 29) into Basolateral amygdala to study the feeding behaviour. MATERIALS AND METHODS: Adult male Wistar albino rats were selected and grouped into control, sham operated control and experimental groups (n = 6 each) Orexin was infused in two doses (3 nmol/ul, 30 nmol/ ul) and TCS-OX2-29 (10 ug/ul) was infused in another group. Sequential Food intake and water intake were measured at 1, 2, 4, 6, 12 hours and intake for the day was also recorded in all groups and the results (mean +/- SEM) were statistically analyzed by Kruskal Wali's test and p < 0.05 was considered significant. RESULTS: The food intake and water intake were significantly increased (p < 0.01) in the high dose group though the increase in the low dose treated animals was less. Injection of Orexin B antagonist decreased the food and water intake significantly. DISCUSSION AND CONCLUSION: The results suggest that Orexin plays a role in the modulation of feeding behaviour. In the lower doses it did not show significant effect. At higher doses, the effect was marked. The role of orexin in ingestive behaviour is further confirmed by the action of antagonist infusion, which resulted decrease in the feeding activities. PMID- 26685507 TI - Sphygmomanometric Blood Pressure Drop on Consecutive Measurements: The Search for a Cause. AB - This study was inspired by our oft-noted observation that the first sphygmomanometric reading of blood pressure (BP) is invariably higher than the subsequent ones recorded immediately thereafter. The objectives of this study were to establish the statistical validity of this observation and further, to probe the possible causes of the same. The sphygmomanometric BP was recorded in 30 non-obese young adults using two different protocols. In protocol-1, BP in the left arm was repeated thrice in quick succession, both in standing and supine postures. In protocol-2, BP was recorded in the supine position six times in quick succession, thrice in the left arm and immediately thereafter, thrice in the right arm. Data was compiled and analysed using appropriate statistical tests. In protocol-1, a statistically-significant drop in the blood pressure was consistently noted between quickly consecutive measurements in both standing and supine postures. Importantly, this pressure drop was not significantly affected by posture. In protocol-2, significant pressure drop was recordable from both arms. These findings rule out baroreflex as a cause of the pressure-drop on consecutive measurements and suggest a likely role of tissue compaction in the same. PMID- 26685506 TI - Evaluation of Visual Evoked Potential (VEP) in Patients With Chronic Obstructive Pulmonary Disease (COPD). AB - Chronic Obstructive Pulmonary Disease (COPD), a progressive and partially reversible disease, has drawn world-wide attention for its moderate prevalence rate and causing central and peripheral neuropathy. Considering its severity in causing visual pathway impairment, the present investigation was carried out to find out the functional integrity of the visual pathway through visual evoked potentials (VEP) and to determine the factors influencing the condition in COPD patients. A total of 30 COPD patients of both sexes, classified according to the severity of the disease based on spirometric indices, were subjected to VEP testing and series of wave forms were measured and compared with equal number of control subjects. The latency of N75 and P100 were prolonged (P < 0.01) and the P100 amplitude was reduced significantly (P < 0.01) in COPD patients. Thus, the influence of COPD causing the optic neuropathy is apparent from the significant VEP changes. Non-invasive procedure can possibly be utilized as a routine screening test for COPD patients for better medical care. PMID- 26685508 TI - Effect of Dual-tasking on Visual and Auditory Simple Reaction Times. AB - Visual and auditory simple reaction times were measured in Sri Lankan young adults to see the effect of dual-tasking on reaction time. Reaction times were measured using a reaction time program in a computer. Subjects responded to stimuli by pressing the spacebar with their dominant index finger. Visual and auditory simple reaction times (ms) in males (mean +/- SD) were 293.5 +/- 42.4, 302.2 +/- 41.9 respectively. In females respective values were 315.1 +/- 55.5, 313.1 +/- 45. Males had statistically significant faster reaction times (p < 0.05) than females. The type of stimuli had no statistically significant effect (p > 0.05) within the same sex. Dual-tasking significantly increases (p < 0.05) both reaction times in both sexes. In females, dual-tasking affects simple auditory reaction time significantly more than simple visual reaction time (p < 0.05). PMID- 26685509 TI - Spirometric Assessment in Juvenile Idiopathic Arthritis. AB - OBJECTIVE: To estimate the prevalence of abnormal spirometry in Juvenile idiopathic arthritis (JIA) patients and to evaluate its relation with subtype, gender, disease activity and methotrexate therapy. METHODS: A cross-sectional study was carried out involving 5-12 years old JIA patients. Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, Forced expiratory flow between 25-75% of vital capacity (FEF25-75%) and peak expiratory flow rate (PEFR) were measured. RESULT: Out of 33 patients, 18 were male. Six patients had oligoarthritis, 16 had polyarthritis and 11 had systemic JIA. Seventeen patients had clinically inactive disease and 16 received methotrexate. None had respiratory symptoms. Thirteen patients had decreased FVC with normal FEV1/FVC. One had decreased FEV1 and FEV1/FVC with normal FVC. Decreased FEF25-75% was found in 4 and decreased PEFR in 8 patients. JIA subtypes differed significantly with regard to prevalence of decreased FVC and FEV1. CONCLUSION: Abnormal spirometry was present in 13 patients and affected all subsets in terms of subtypes, gender, disease activity and methotrexate therapy. PMID- 26685510 TI - Toxic Chemical from Plastics Attenuates Phenylbiguanide-induced Cardio respiratory Reflexes in Anaesthetized Rats. AB - Bisphenol A (BPA) attenuated phenylbiguanide (PBG)-induced cardio-respiratory reflexes involving decreased vagal afferent activity. BPA leaches out from plastics thus it is expected that chronic exposure to plastic boiled (PBW) water will also produce similar changes. Therefore, the present study was undertaken to evaluate the effects of chronic ingestion of PBW on PBG evoked reflexes and were compared with BPA. Adult female rats were ingested BPA containing pellets (2 ug/kg body weight)/PBW/tap water (ad libitum) for 30 days. On day 30, the animals were anaesthetized and BP, ECG and respiratory excursions were recorded. Further, PBG was injected intravenously to evoke cardio-respiratory reflexes and at the end lungs were excised for histopathological examination. BPA concentration in PBW was 6.6 ug/ml estimated by HPLC. In rats receiving tap water, PBG produced bradycardia, hypotension and tachypnoea. In PBW/BPA treated groups, PBG-induced reflexes were attenuated significantly along with emphysematous and consolidative changes in lungs. The present results indicate that PBW attenuates the protective cardio-respiratory reflexes and also produces histopathological changes in lungs. PMID- 26685511 TI - Perinatal Exposure to Low-dose Nonylphenol Specifically Improves Spatial Learning and Memory in Male Rat Offspring. AB - 4-Nonylphenol (NP) has weak estrogen-like activity, and can therefore act as an endocrine disruptor. This study examined the effects of perinatal exposure to low dose NP on learning and memory, general activity, and emotionality in male rat offspring. Dams were orally administered 1 or 10 mg/kg/day of NP or vehicle from gestational day 10 to postnatal day 14. The male offspring were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) used to assess spatial learning and memory. In the MAZE test, times to reach goal (food) for both groups treated with NP were significantly shorter than those for the control group. In other behavioral tests (the open-field, elevated plus-maze, and step-through passive avoidance tests), NP did not affect any of each behavioral parameter. Thus, this study indicates perinatal exposure to low dose NP specifically improves spatial learning and memory in male rat offspring. PMID- 26685512 TI - Effects of Hydroalcoholic Extract of Watercress (Nasturtium Officinale) Leaves on Serum Glucose and Lipid Levels in Diabetic Rats. AB - OBJECTIVE: Hyperlipidemia is a known complication of diabetes mellitus and predisposes to coronary heart disease. The lowering of total cholesterol and low density lipoprotein (LDL)-cholesterol should reduce the incidence of coronary disease. The aim of the present study was to examine the antihyperlipidemic and antidiabetic effects of the hydroalcoholic extract of watercress (Nasturtium officinale) leaves in streptozotocin-induced diabetic rats. METHODS: Female Wistar rats were randomly divided into 4 groups: control, diabetic and diabetic rats treated with the extract of watercress (Nasturtium officinale) at doses of 100 and 200 mg/kg. Diabetic rats received the watercress extract daily in drinking water for 4 weeks since the day after diabetes confirmation. The levels of serum glucose and lipids were spectrophotometrically measured in all groups at weeks 0 (before diabetes induction), 2 and 4. RESULTS: There was a significant increase in serum glucose, triglycerides, total cholesterol, and LDL-cholesterol in streptozotocin-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. The treatment of diabetic rats with hydroalcoholic extract of watercress (Nasturtium officinale) leaves over a 4-week period significantly reduced serum glucose, total cholesterol and LDL- cholesterol in comparison with diabetic untreated rats. CONCLUSION: Our findings demonstrated that a 4-week treatment with watercress extract at a dose of 200 mg/kg has hypoglycemic and hypolipidemic effects in streptozotocin-diabetic rats. This implies that the consumption of watercress leaves can be helpful in reducing the complications of hyperglycemia and dyslipidemia associated with diabetes. PMID- 26685513 TI - Learning Style Preferences of Undergraduate Dental Students of a North Indian Dental College. AB - This study was undertaken to determine the learning style preferences of first and 2nd year BDS students by administering VARK questionnaire. Stepping stone method was used to identify sensory modality preference of each student. 51% students preferred single mode of learning style (27% kinesthetic, 15% aural, 6% read/write and 3% visual mode of learning style). 49% students preferred multiple modes (23% bi-modal, 17% tri-modal, 9% had quad-modal preference). The mean V, A, R, K scores were determined and compared using Mann-Whitney U test. V score of 2nd year was significantly higher compared to 1st year (p value = 0.012). V score of females was significantly higher than that of males (p value = 0.004). The results showed diversity in preference of learning style of students. This diversity necessitates a change from traditional teaching (aural lecture and flowcharts/diagrams) to active learning strategies, for a more productive educational experience. PMID- 26685514 TI - Level of Mercury Manometer With Respect to Heart: Does it Affect Blood Pressure Measurement? AB - Measurement of blood pressure is an integral part of clinical examination. Over the years various types of instruments have been used to measure blood pressure but till date the mercury sphygmomanometer is regarded as the gold standard. However, there is a myth prevalent among health professionals regarding the level of the manometer in relation to heart at the time of measuring of blood pressure. Many professionals insist that it has to be placed at the level of the heart. We argue that the limb from which pressure is measured must be at the heart level rather than the manometer. We conducted a study in which we measured the blood pressure in adults by placing the manometer at three different levels with respect to the heart. The values of blood pressure obtained at all levels were similar and did not show any statistically significant difference. We therefore conclude that the level of sphygmomanometer per se does not affect blood pressure measurement. PMID- 26685515 TI - Hearing Sensitivity in 40-60 Years Old Hypertensive Male Adults. AB - Declining hearing sensitivity is appreciated as a normal age related change. However, studies reveal that health variables other than age play significant role in hearing impairment over time. Hypertension is one such variable. The objective of this study was to assess whether the hypertension has an accelerating effect on age related reduction in hearing function in males in the age group of 40-60 years. Systolic and Diastolic blood. pressure and Pure Tone thresholds in frequency range 250-8000 Hz were measured in 30 known hypertensive (HT) male subjects in the age group of 40-60 years and 30 age and sex-matched normotensive (NT) controls. There was no significant difference in hearing thresholds at various frequencies between HT and NT group and between uncontrolled HT (n = 15) and controlled HT subgroups (n = 15). However, a significantly positive correlation between the systolic blood pressure and Air conduction thresholds at 4000 Hz and 8000 Hz and Bone conduction thresholds at 4000 Hz were noted in uncontrolled HT subgroup. Results of the current study demonstrated towards the potentially negative impact of uncontrolled hypertension on the auditory function in the age group of 40-60 years. PMID- 26685516 TI - The Premedieval Origin of Portolan Charts: New Geodetic Evidence. AB - Portolan charts are highly realistic medieval charts that show remarkably accurate coastlines of the Mediterranean and the Black Sea. They emerged suddenly, without any predecessors or a clear developmental path, in Italy during the thirteenth century. There is broad scholarly agreement that these charts are original creations of European medieval culture. However, corroborating evidence is lacking, and a convincing explanation of the method of their construction has so far not been provided. In this essay it is demonstrated by means of geodetic analysis that the overall shape of the coastlines corresponds closely to that on a modern map based on the Mercator projection. It is further demonstrated that this correspondence cannot possibly be due to chance. Consequently, the existence of a Mercator or Mercator-like map projection on portolan charts is incompatible with the assumed medieval origin of these charts. Portolan charts are far more sophisticated than has hitherto been recognized. Their construction was well beyond the capabilities of cartographers from either medieval Europe or the Arabic-Islamic world. This conclusion serves to reopen the question of the origins of the geometric data and the construction methods that until now have appeared to underlie medieval portolan charts. PMID- 26685517 TI - Unpuzzling American Climate: New World Experience and the Foundations of a New Science. AB - In the early exploration and colonization of the Americas, Europeans encountered unfamiliar climates that challenged received ideas from classical geography. This experience drove innovative efforts to understand and explain patterns of weather and seasons in the New World. A close examination of three climatic puzzles (the habitability of the tropics, debates on the likelihood of a Northwest Passage, and the unexpectedly harsh weather in the first North American colonies) illustrates how sixteenth- and seventeenth-century observers made three intellectual breakthroughs: conceiving of climates as a distinct subject of inquiry, crossing the hitherto-separated disciplines of geography and meteorology, and developing new theories regarding the influence of prevailing winds on patterns of weather and seasons. While unquantified and unsystematic, these novel approaches promoted a new understanding of climates critical to the emergence of climate science. This study offers new insights into the foundations of climatology and the role of the New World in early modern science. PMID- 26685518 TI - Epistemological Dizziness in the Psychology Laboratory: Lively Subjects, Anxious Experimenters, and Experimental Relations, 1950-1970. AB - Since the demise of introspective techniques in the early twentieth century, experimental psychology has largely assumed an administrative arrangement between experimenters and subjects wherein subjects respond to experimenters' instructions and experimenters meticulously constrain that relationship through experimental controls. During the postwar era this standard arrangement came to be questioned, initiating reflections that resonated with Cold War anxieties about the nature of the subjects and the experimenters alike. Albeit relatively short lived, these interrogations of laboratory relationships gave rise to unconventional testimonies and critiques of experimental method and epistemology. Researchers voiced serious concerns about the honesty and normality of subjects, the politics of the laboratory, and their own experimental conduct. Their reflective commentaries record the intimacy of subject and experimenter relations and the plentiful cultural materials that constituted the experimental situation, revealing the permeable boundaries between laboratory and everyday life. PMID- 26685519 TI - The Reinvention of General Relativity: A Historiographical Framework for Assessing One Hundred Years of Curved Space-time. AB - The history of the theory of general relativity presents unique features. After its discovery, the theory was immediately confirmed and rapidly changed established notions of space and time. The further implications of general relativity, however, remained largely unexplored until the mid 1950s, when it came into focus as a physical theory and gradually returned to the mainstream of physics. This essay presents a historiographical framework for assessing the history of general relativity by taking into account in an integrated narrative intellectual developments, epistemological problems, and technological advances; the characteristics of post-World War II and Cold War science; and newly emerging institutional settings. It argues that such a framework can help us understand this renaissance of general relativity as a result of two main factors: the recognition of the untapped potential of general relativity and an explicit effort at community building, which allowed this formerly disparate and dispersed field to benefit from the postwar changes in the scientific landscape. PMID- 26685520 TI - Focus: Bounded Rationality and the History of Science. Introduction. AB - Historians of science see knowledge and its claimants as constrained by myriad factors. These limitations range from the assumptions and commitments of scientific practitioners to the material and ideational contexts of their practice. The precise nature of such limits and the relations among them remains an open question in the history of science. The essays in this Focus section address this question by examining one influential portrayal of constraints- Herbert Simon's theory of "bounded rationality"--as well as the responses to which it has given rise over the last half century. PMID- 26685521 TI - Of Models and Machines: Implementing Bounded Rationality. AB - This essay explores the early history of Herbert Simon's principle of bounded rationality in the context of his Artificial Intelligence research in the mid 1950s. It focuses in particular on how Simon and his colleagues at the RAND Corporation translated a model of human reasoning into a computer program, the Logic Theory Machine. They were motivated by a belief that computers and minds were the same kind of thing--namely, information-processing systems. The Logic Theory Machine program was a model of how people solved problems in elementary mathematical logic. However, in making this model actually run on their 1950s computer, the JOHNNIAC, Simon and his colleagues had to navigate many obstacles and material constraints quite foreign to the human experience of logic. They crafted new tools and engaged in new practices that accommodated the affordances of their machine, rather than reflecting the character of human cognition and its bounds. The essay argues that tracking this implementation effort shows that "internal" cognitive practices and "external" tools and materials are not so easily separated as they are in Simon's principle of bounded rationality--the latter often shaping the dynamics of the former. PMID- 26685522 TI - Hypothesis Bound: Trial and Error in the Nineteenth Century. AB - Like so many things, "trial and error" has a history. The term first emerged as the name for a technique in eighteenth-century mathematics pedagogy. In the nineteenth century, psychologists and biologists transformed "trial and error" from a mathematical tool into a developmental theory, one that could explain both the learning mind and life on earth. "Trial and error" can thus be seen as a case of the larger process whereby the tools we use to explain the world do not just influence but in many ways become our explanations--a process that the psychologist Gerd Gigerenzer has called the "tools-to-theories" heuristic. This essay uses Gigerenzer's concept to frame the evolution of "trial and error." By the end, it suggests how the historical relationship between tools and theories prompts a reconsideration of the terms and assumptions historians of science use in their own work. PMID- 26685523 TI - For What It's Worth: Historical Financial Bubbles and the Boundaries of Economic Rationality. AB - This essay is a historical and epistemological exploration of a traditionally crazy economic event: the financial bubble. Venturing into two different moments in the history of economic thinking, it investigates financial bubbles as epistemic frontiers, where rationality has reached its limits. The first half forays into late twentieth-century economics. Since 1980, an interpretive battle over the ir/rationality of bubbles has made those peculiar events, long beyond the pale of the rational, contested terrain on which the limits of rationality have been fought out. The essay's second half turns to one historical crisis, the South Sea Bubble. For contemporaries in 1720, the bubble was a different kind of epistemic frontier. As they tried to reckon what South Sea Company stock was worth, investors were confronted not with clearly rational or irrational choices but with a decidedly unruly collection of similarly plausible calculations. The story of 1720 suggests that studying historical confusion might be a profitable enterprise for scholars of the economic and epistemological past. PMID- 26685524 TI - Heuristic Medicine: The Methodists and Metalepsis. AB - In the first century B.C.E., a group of Greek physicians called the Methodists denied that medicine could be based on such "hidden causes" as humors, atoms, or elements. They argued that the inner workings of the body were ultimately unknowable, existing beyond the limits of human knowledge and inference. Yet they insisted that medical certainty was still possible, claiming that every disease shared one of three directly apprehensible "manifest commonalities"--stricture, laxity, or some mixture of the two. Medicine could therefore be a science; it was simply noncausal in structure. This essay examines these medical theories in light of Herbert Simon's concept of "bounded rationality," suggesting that the Methodists were proposing a type of medical "heuristic" in response to the limitations of human knowledge and processing power. At the same time, the essay suggests that such an epistemology had its consequences, setting up an ontological crunch whereby the demands formerly placed on diseases and their causes transferred to "affections" and the commonalities, with successive generations of Methodists disagreeing about the status of symptoms, signs, and diseased states. Borrowing vocabulary from the Methodists themselves, the essay calls the consequent ontological slippage between causes and effects "metalepsis". PMID- 26685525 TI - Simon and the Sirens: A Commentary. AB - Even in its extended usage, the concept of bounded rationality bears the birthmark of its origins in economics. First and most obviously, it is about seeking the most efficient (not necessarily the best) means toward a given end, whether that is curing patients or proving theorems. Second, the means are whittled down to the most parsimonious possible, not only acknowledging cognitive limitations but actually imposing them, whether in the form of Morgan's canon, Methodist agnosticism about causes, or Entscheidungsproblem-like restrictions on the acceptable formulation of mathematical proofs. Third, these parsimonious restrictions all tend to minimize the role of reasonable deliberation in rationality, albeit in different ways. As an object of inquiry for the history of science, bounded rationality has great promise. But as a model of the history of science, as one long exercise in bounded rationality, its utility may apply more to future than past science. PMID- 26685526 TI - The Fabrica Remade: A New Translation of the De Humani Corporis Fabrica Libri Septem (1543, 1555) of Andreas Vesalius. PMID- 26685527 TI - Albert Einstein and the History and Philosophy of Science. PMID- 26685528 TI - [Champions]. PMID- 26685529 TI - [Motivating added value in nursing]. PMID- 26685530 TI - [Coordinated care is paying off]. PMID- 26685531 TI - [Also addressing addiction]. PMID- 26685532 TI - ["My most instructive time"]. PMID- 26685533 TI - [Giving a voice to those who don't have one]. PMID- 26685534 TI - [Skill and grade mix from the perspective of older nurses]. PMID- 26685535 TI - ["Nursing removed from helping career"]. PMID- 26685536 TI - [Building bridges between nursing practice and science]. PMID- 26685537 TI - [Obesity and organ transplantation]. PMID- 26685538 TI - ["Every day the entire landscape of nursing"]. PMID- 26685539 TI - [A difficult entry into the profession]. PMID- 26685540 TI - [Invaluable, priceless]. PMID- 26685541 TI - [Nurses make a difference!]. PMID- 26685542 TI - [Discovering the clinical evaluation]. PMID- 26685544 TI - [Creativity at the heart of nursing units]. PMID- 26685543 TI - [Impact of a school for asthma]. PMID- 26685545 TI - [The other side of the tube]. PMID- 26685547 TI - [The (added) value makes the difference]. PMID- 26685546 TI - [How much does it cost?]. PMID- 26685548 TI - [The thesis of science what is it for?]. PMID- 26685549 TI - [Care: a professional concept to human limitations?]. AB - Recent transformations in our society have brought to light new forms of care in which the carer/nurse relationship has been re-considered, and that have emphasised the multiple and varied forms of vulnerability. Through different theoretical approaches, we will present the various aspects of care in history and its re-thinking in the social, ethical and political context of the 2000's. We have focused on the various facets of care and their impacts for the nursing profession. PMID- 26685550 TI - [Care between ethics, work and political]. AB - Down to the roots, the ethics of care have stood up a "different voice". Building on Carol Gilligan's works, the concept was developed widely in opposition with the rational and universalist aspect of Kant's moral philosophy. However, it also appears that this vision of care runs counter sets the three other main dominant moral theories, ie, utilitarism, John Rawls' procedural ethics and the Aristotelian virtue ethics. We may assert that the care theory presents itself as a contextualized moral theory aiming at taking into account others' vulnerability, in a practical way. Hence, the general term of "care" may encompass the notions of "help", "support" and "healing process", which, in France, for have often been opposed for varied reasons--historical, economical, psychological, professional etc... Switching from a moral position to a professional and practical activity, the concept of care has now undeniably taken on now a social and political dimension. PMID- 26685551 TI - [Beyond the treatment and care: the History of the doctor-patient relationship as a source to think the nurse-patient relationship in the XXIst century]. AB - The history of the relationship between doctors and patients shows that it is possible to find traces of attention from doctors towards patients as far back as the Antiquity. Nevertheless, at that time, this solicitude is made essentially in the name of nature through the sick individual. With the Middle Ages and the rise and growing importance of Christianity, the notion of person appeared, rising beyond the physical limits of the individual. At that time, the solicitude is then made in the name of God transcending, in that way, the sick person. It is only at the end of the XIXth century, with the movement of social transformation and secularization of the medical care, that it is possible to detect the notion of subject in the medical relation as proved by the emergence of the psychoanalysis. But at the same time, the spectacular evolution of medicine in its scientific component and its increasing importance during the next century made that it focused mainly on a naturalistic vision of the world of the medical care, to the detriment, most of the time, of a personal vision taking into account the deep-rooted social characters of the sick subject. From then on, the nursing profession could be seen, at the beginning of the XXIth century, as complementary to the medicine, through the development and the implementation of a dominant personal relation type without neglecting the naturalistic relation type. This prospect could be possible on the condition of developing the scientific knowledge allowing to give consistency and thickness to this way of seeing and acting centered on the person. An approach doubtless inspired by the care, yet going further its emotional and ethical meaning, in order to understand and to act better. PMID- 26685552 TI - [The place of caring in the nurse's diagnosis in patient education]. AB - This report relates to the research on the benefits and the use of the caring in the nurse's diagnosis practice in patient education. The theoretical framework is built thanks to Joan Tronto's work on caring. Caring consists of taking care of other people's concerns and needs. This raises the issue of knowing how nurses deal with caring during the educational diagnosis. The qualitative research conducts through four nurses, receiving patients in an educational program in a diabetes department of a Paris based hospital. The analysis of the semi structured and explicative interviews shows how nurses care about and take care of patient in thoughts and in their nursing practice. In the educational program, they set up a particular plan to interview the patient at his arrival. This plan, similar to a spatio-temporal ritual, tends to foster the clinical interview and the emotional assessment due to the impact of the chronic condition on the patient's live. This enables to make an appropriate educational's diagnosis. PMID- 26685553 TI - [Care in health care and in nurses' informal learning practices]. AB - INTRODUCTION: in everyday practice, nurses combine both the care and the cure. BACKGROUND: changes in the hospital environment alter care practices. Nurses adapt by conducting informal learning every day to be competent in professional situations. The way they do that approximate their way to have concern for the other, to take care of the patient in care practices. GOAL: this article aims to show the existing similarities between the care of the caregiver to a patient and the care of the caregiver to another caregiver, i.e. a peer, in informal learning in the workplace. METHOD: qualitative research of comprehensive type with a population sample of thirty nurses in two fields of inquiry, a hospital and a clinic. Two tools are used: a log collecting nurses learning processes day by day for six weeks and two interviews, one to introduce the log filling instructions and the other to facilitate the understanding of written texts. On that occasion, the care is mentioned. The results highlight the similarities between the care in caregiving activities and in learning processes, in terms of designing of care and purpose, of position in considering the concern for others and their vulnerability. CONCLUSION: the care is transverse in nursing practice, whether in care or learning process. PMID- 26685554 TI - [From humanism to nihilism: dialectics on Jean Watson's caring theory]. AB - INTRODUCTION: nursing today is heir to values that have developed over many years. In addition to the values of human care, present-day nursing embraces values that shape our modern world. This dialectical study first traces the evolution of a number of the traditional values associated with human care that nursing has retained. It goes on to show how some of the values of human care have been cast aside in favour of modern--neoliberal, technocratic and bureaucratic--values which have in turn given rise to disturbing problems of instrumentalization. Watson's theory of caring proposes two ways to remedy such instrumentalization: espousing a transcendental, metaphysical mode of thought and adopting an altruistic humanism. However, many critics have questioned the theoretical consistency and very legitimacy of the theory as a means of dealing with instrumentalization. AIM AND METHODOLOGY: this study analyses Watson's proposals, using a Nietzschean dialectic approach to test them and to suggest possible solutions. Significant problems in terms of both consistency and relevance are brought to light, tending to refute Watson's notions. RESULTS AND DISCUSSION: the study findings suggest that the application of Watson's theory may paradoxically perpetuate dualism and nihilism and, rather than curb their invasive impact, lead inevitably to a conversion to instrumental values. CONCLUSION: it's suggested an alternative, ethics-of-life approach based on the synthesis of our dialectics that would foster a return to, and respect for, humanity's essential nature. PMID- 26685555 TI - [Care in pediatric]. AB - INTRODUCTION: pediatric care is a context in which the concept of specific care should be thought over, hereby suggesting a reflection on formalizing the notion of pediatric care. CONTEXT: the concept of care applied to nursing care offers a framework for professionals. Pediatric care presents specificities which lead to adapting the concept of care which is only formalized globally or in specific cases such as neonatology. RESULTS: according to various theories, the formalization of a concept specifically for children aged 1 to 15 seems to be lacking. DISCUSSION: building a framework for the concept of pediatric care, based on recommendations and evidence, could be useful to formalize the work of pediatric nurses. The notion needs to be more clearly defined. CONCLUSION: the notion of pediatric care regroups conceptual trends adapted to the specificities of pediatric care, providing practical considerations. PMID- 26685556 TI - [Care, the caring, the cure and the caregiver]. AB - Due to the multiple meanings of the concept of care and its diverse cultural meanings, the purpose of this article is to address this concept, starting with clarification of its etymological origins. In addition to this clarification, the objectives of this paper are to highlight the rapport between care and cure, the implications of care in health care team management. The etymological analysis is made starting from encyclopaedic writings, to discuss the original meaning of the concept. The results of this analysis show that the original meaning of care is anchored on affects and feeling, lead to caring. Therefore, a personal dimension is inherent to it. This reflection tries to show that care does not oppose to cure, but that it is imperative to incresae nurses to the personal dimension in care to become caring with the management support. The conclusion reveals that a personal dimension of caring, supported by human values associated, participate to the professional dimension of the nursing role. Thus, these two dimensions that must grow together, are unavoidable for nursing pratice. PMID- 26685557 TI - [Care in nursing in Brazil]. AB - The aim of this paper is to propose a reflection about the care in Brazilian nursing considering some theorists. For doing so, we have started with a discussion about the anglo saxon concept of care and possible translations into Portuguese language. After this, some authors who have theoretically subsidized some scientific productions in healthcare and specifically in Brazilian nursing are introduced. Within this analysis, the presence of different ways of thinking nursing care were identified, but in relation to the concept of care, as it has been proposed in France, there are not too many studies and scientific research. However, despite the limitation of academic research about care in health area, particularly in Brazilian nursing, it is possible to observe that its conceptual assumptions tangent certain bets made in some health policies such as the National Humanization Policy and the Health Continuing Education Policy, as well as in the organization of the Unified Health System, that focus on the integrality of patient care. PMID- 26685558 TI - [The teaching of care in IFSI]. AB - Instituts de Formation en Soins Infirmiers (IFSI) are in charge of nurses initial training. As such, they take part in the transmission of care. Care is a fundamental practical philosophy, an infrastructure rather than a superstructure, on which rest every aspects of nursing. It can be defined as a psychological or mental attitude that results in a corporal and verbal attitude aimed at facilitating person-to-person singular communication. Has the July 2009 reform of nursing education applied by IFSI any influence on that postulate? The redistribution of roles between the various actors of nursing education (IFSI instructors, field training practitioners and University teachers) raises questions. What do the new syllabus and the reality of teaching methods and contents show? What is the present status of care transmission in nursing education? And what are its future prospects? PMID- 26685559 TI - [Amy et Jake. Care, reflexivity, negativity]. AB - Two extracts of ethnographic investigations come to show that the care cannot be regarded as an effective classifying concept. Resting on only one ethical injunction, it is unable to seize negativity inherent in the trades of the care, in particular certain returns on its own practice and certain new reports of classes. However, it appears completely detrimental not to seek to analyze and interpret this material not-in conformity suitable for the investigation or the practices of care. Finally, a criticism artificial positivity of the care returns to one time a broader criticism which hardly any more tolerates the dissonance of the ordinary life. PMID- 26685560 TI - [Research and nursing]. PMID- 26685561 TI - [USING URINARY STRIPS]. AB - INTRODUCTION: Urinalysis using reactive strip is a commonly used in clinical practice. Although mainly indicated as first step test when a urine infection it suspected, it may also be a helpful tool in the management of a wide range of disorders. DEVELOPMENT: Standard urine test strips may comprise of up to 10 different chemical pads or reagents (leukocytes, nitrites, pH, glucose, proteins, ketones, bilirubin, urobilinogen, density and blood) that allow a qualitative and semiquantitative analysis of a urine sample. The test method consists of immersing the strip completely in a well-mixed sample of urine and left to stand for the time necessary for the reactions to occur (which is variable depending on the manufacturer). Finally the colors that appear are compared against a specific chromatic scale provided. Several factors may influence the results causing a significant number of false positives and negatives. Such limitations should always be taken into account when reading the test. DISCUSSION: Despite clinical features lead to the suspicion of an infection, urine test strips is a fast screening test that may reinforce the diagnosis. The combination of dysuria, frequency and emergency, hematuria, pain and sensibility in the pelvis reaches a positive predictive value to identified a urine infection of 90 %. When only dysuria and emergency or high frequency are present, the such probability diminishes to 70-80%, and, when dysuria is the only symptom, it drops to 25%. CONCLUSIONS: Despite urine test strips is a fast, easy and cheap method for the diagnosis and follow-up of several diseases, results are fairly heterogeneous and may be influenced by external factors. Therefore a cautious interpretation if advised. Sensibility and specificity of urine test strips is widely variable (S 46%-86% and E 17%-93%). Although the highest diagnostic values are obtained at primary care centers, where such tests are routinely used in a diverse population, the number of false positives is still high. This issue should be taken into account and a proper differential diagnosis of a positive result is mandatory in all cases. More studies are needed to assess the real sensibility and specificity of urinary reactive strips. PMID- 26685562 TI - [VACCINES]. AB - Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs. PMID- 26685563 TI - [HIGH-RISK CHRONICALLY ILL PATIENTS: DIAGNOSTICS, RESULTS AND NURSING INTERVENTIONS UPON DISCHARGE]. AB - It is after the implementation of the new nursing evaluation/ planning care registers (PCE) in the medical record and the updating of the document/circuit of the All-clear Ensuing Care Report (ICCA) with NANDA, NOC, NIC (NNN) in the first months of the year 2013, that we are contemplating the fulfillment of a descriptive/cross-section study so as to know diagnostics, results and nursing interventions upon discharge of high-risk chronically ill patients and qualitatively in medical hospitalization units and in palliative care. The results obtained at a quantitative level, with an implementation degree of 83 and 94 per cent, respectively, are extremely encouraging. Regarding the quality of care planning, we have identified for the first time in our hospital both the NANDA, the NOC and NIC with the prevalence degree in the units studied. PMID- 26685564 TI - [EVOLUTION OF REVISTA ROL DE ENFERMERIA (1978-2008): A BIBLIOGRAPHIC ANALYSIS]. AB - Revista ROL de Enfermeria was the first journal of nurses and adressed to nursing published with the birth of Spanish democracy, indexed soon Medline/PubMed. This paper analyzes the changes in the structure and function of the magazine. Highlights two facts. The journal ROL expresses the transformation of the new universitary nursing, and how was adapting to scientific standards: although not increased the number of original articles, was normalizing their structure, bibliography or citations pattern, and also the scientific writing style. PMID- 26685565 TI - [BURNOUT: PREVENT IT IS TO ADVANCE]. AB - The exercise of nursing and medicine is a gratifying work for the one who exercises it, though, sometimes, the daily reality of the hospitals and the peculiarity of the sector cause that the sanitary personnel presents pictures of stress with more assiduity that another type of professionals, what produces the appearance and the development of the symptoms associated to burnout syndrome. Later, we will try to analyze the principal reasons for which this syndrome appears, the consequences and, very specially, the measures of prevention and treatment. PMID- 26685566 TI - [OPTIMIZATION OF GLUCOSE METABOLISM IN PATIENTS UNDERGOING THERAPEUTIC HYPOTHERMIA AFTER SUDDEN CARDIAC ARREST]. AB - OBJECTIVE: Therapeutic hypothermia (TH) is recommended to improve survival and neurologic prognosis in sudden cardiac arrest (SCA) survivors. There are few data aboutglycemic levels in these patients. The aim of this study is to evaluate the glycemic control using a specific protocol in this group ofpeople. METHOD: A retrospective analysis of the patients receiving TH in our institution, between January 2010 and March 2013,. was performed. Baseline characteristics, in hospital prognosis and glycemic levels during different stages of the TH were analyzed. RESULTS: From a total of 55 patients suffering a SCA, 49 patients underwent TH and received a specific insulin protocol. The mean age was 57.5 +/- 12.8 years, the main cause of SCA was ischemic (76%) and ventricular fibrillation was the most frequent first rhythm detected (55%). Regarding glycemic alterations as each stage of TH, a high rate of glycemic alteration was observed in the induction stage, decreasing after starting the insulin protocol (induction stage: 95.9%; maintenance stage: 89.8%; rewarming stage: 69.4%; p = 0.001). With respectto clinicresults, there were low rates of severe hypoglycemia (12%), in hospital mortality (20%) and anoxic encephalopathy (27%), with a high rate of infections (75%). CONCLUSIONS: The implementation of a specific insulin protocol in patients receiving TH contributes to improve the blood glucose levels. Further studies are needed to evaluate the clinical impact of these protocols in this group ofpatients. PMID- 26685567 TI - [ETHICAL CONFLICTS AT THE END OF LIFE FROM NURSE PERCEPTION]. AB - INTRODUCTION: Current medicine tends to dehumanize the end of life process, which contributes to generate certain ethical conflict to nurse staff MATERIAL AND METHOD: The major scientific datadas research. RESULTS: The four main ethical conflicts detected are: decisions making, communicating information, futile treatments and hydration and artificial feeding. DISCUSSION: The nurses suffer moral distress with ethical conflicts by the obligation of safeguard the dignity and rights of their patients. CONCLUSIONS: The lack of training and experience to treat ethical problems contribute to increase nurse disconfort. PMID- 26685568 TI - [IMPACT OF A PSYCHOEDUCATIONAL GROUP INTERVENTION FOR PATIENTS WITH MILD/MODERATE DEPRESSION IN PRIMARY CARE CONSULTATIONS]. AB - OBJECTIVE: To analyze the impact of psycho-educational groups for patients with mild/moderate depression in relation to attendance in primary care consultations, the consumption of anxiolytics and antidepressants and the number of days of temporary disability of patients who performed the intervention group versus those not performed. METHOD: Controlled, longitudinal, prospective cohorts in 13 primary care teams of Barcelona city randomized trial. 232 patients, 120 intervention group and 112 in the control group. The study variables were: sex, age, marital status, nationality, education level, employment status, consumption of anxiolytics and/or antidepressants, number of working days, depressive symptoms, quality of life, co-morbidity and attendance in consulting physician and primary care nurse. RESULTS: 69.7% of the total sample were healthy persons frequenting the control group and intervention in the nursing represented a reduction of 2 points in the average number of visits made during the pre intervention year and the year after the intervention. This was not affected attendance in the control group and in visits to the family doctor. A reduction was observed in the number of casualties of those who have made thegroup intervention. CONCLUSIONS: The psychoeducational group intervention for patients with mild/moderate depression makes decrease the assistance frequency of the patients to nurse consultory. Patients who have assisted to psychoeducational group intervention tend to apply less for the medical leave. PMID- 26685569 TI - [Care to the family of terminally ill patients (2)]. PMID- 26685570 TI - [XXXII National Congress of Mental Health Nursing. 2nd International Conference of Mental Health Nursing. Delivery of XIII Research Award ANESM]. PMID- 26685571 TI - [Nursing and dog assisted therapy]. PMID- 26685572 TI - [Investen-isciii convenes in Cuenca, the coming month of November, all research nurses]. PMID- 26685573 TI - [Conclusions XII AMEG Day]. PMID- 26685574 TI - [Interview with Francisco Javier Pastor Gallardo]. PMID- 26685575 TI - [Interview with Daniel de Roque Blanch]. PMID- 26685576 TI - Oro 2.0 Helps Hospital Leadership Assess Organizational High Reliability. PMID- 26685577 TI - New Alert Discusses Prevention of Patient Falls. PMID- 26685579 TI - POSTING: Fall E-dition Release for Accreditation and Certification Manual Products. PMID- 26685578 TI - Got Standards Compliance Troubles? Proceed to the Portal. PMID- 26685580 TI - How Mississippi Baptist Health System Optimized Its Mid-Cycle Revenue Cycle. PMID- 26685581 TI - Granting Patient Financial Assistance and Setting Charges Under the IRS 501(r) Rules. PMID- 26685582 TI - Leveraging IRS 501(r) Rules to Financially Engage All Patients. PMID- 26685583 TI - Change in Household Spending After Retirement: Results from a Longitudinal Sample. PMID- 26685584 TI - [Difference in responses of major tree species growth to climate in the Miyaluo Mountains, western Sichuan, China]. AB - To explore the responses of different tree species growth to climate change in the semi-humid region of the eastern Tibetan Plateau, we investigated climate growth relationships of Tsuga chinensis, Abies faxoniana, Picea purpurea at an altitude of 3000 m (low altitude) and A. faxoniana and Larix mastersiana at an altitude of 4000 m (high altitude) using tree ring-width chronologies (total of 182 cores) developed from Miyaluo, western Sichuan, China. Five residual chronologies were developed from the cross-dated ring width series using the program ARSTAN, and the relationships between monthly climate variables and tree ring index were analyzed. Results showed that the chronologies of trees at low altitudes were negatively correlated with air temperature but positively with precipitation in April and May. This indicated that drought stress limited tree growth at low altitude, but different tree species showed significant variations. T. chinensis was most severely affected by drought stress, followed by A. faxoniana and P. purpurea. Trees at high altitude were mainly affected by growing season temperature. Tree-ring index of A. faxoniana was positively correlated with monthly minimum temperature in February and July of the current year and monthly maximum temperature in October of the previous year. Radial growth of L. mastersiana was positively correlated with monthly maximum temperature in May, and negatively with monthly mean temperature in February and monthly minimum temperature in March. In recent decadal years, the climate in northeast Tibetan Plateau had a warming and drying trend. If this trend continues, we could deduce that P. purpurea should grow faster than T. chinensis and A. faxoniana at low altitudes, while A. faxoniana would benefit more from global warming at high altitudes. PMID- 26685585 TI - [Application of three heat pulse technique-based methods to determine the stem sap flow]. AB - It is of critical importance to acquire tree transpiration characters through sap flow methodology to understand tree water physiology, forest ecology and ecosystem water exchange. Tri-probe heat pulse sensors, which are widely utilized in soil thermal parameters and soil evaporation measurement, were applied to implement Salix matsudana sap flow density (Vs) measurements via heat-ratio method (HRM), T-Max method (T-Max) and single-probe heat pulse probe (SHPP) method, and comparative analysis was conducted with additional Grainer's thermal diffusion probes (TDP) measured results. The results showed that, it took about five weeks to reach a stable measurement stage after TPHP installation, Vs measured with three methods in the early stage after installation was 135%-220% higher than Vs in the stable measurement stage, and Vs estimated via HRM, T-Max and SHPP methods were significantly linearly correlated with Vs estimated via TDP method, with R2 of 0.93, 0.73 and 0.91, respectively, and R2 for Vs measured by SHPP and HRM reached 0.94. HRM had relatively higher precision in measuring low rates and reverse sap flow. SHPP method seemed to be very promising to measure sap flow for configuration simplicity and high measuring accuracy, whereas it couldn' t distinguish directions of flow. T-Max method had relatively higher error in sap flow measurement, and it couldn' t measure sap flow below 5 cm3 . cm(-2) . h(-1), thus this method could not be used alone, however it could measure thermal diffusivity for calculating sap flow when other methods were imposed. It was recommended to choose a proper method or a combination of several methods to measure stem sap flow, based on specific research purpose. PMID- 26685586 TI - [Estimating nonstructural carbon content of tree crown considering its spatial variability: A case study on Juglans mandshurica and Ulmus japonica]. AB - Using Juglans mandshurica and Ulmus japonica as test materials, we examined the variability in nonstructural carbohydrates (NSC) concentrations in the branches with different basal diameters with a branch analysis method and explored potential errors in estimating the crown-scale NSC content introduced from various sampling protocols. The results showed that organs significantly influenced the crown NSC concentrations for both species. The mean concentrations of the sum of soluble sugars and starch (TNC) of the leaves, new twigs, old branches, and dead branches were 17.6%, 12.6%, 5.7% and 2.9%, respectively. Most of the NSC concentrations in leaves and new twigs varied insignificantly with basal diameter, age, length and height of the branch. However, the NSC concentration in old branches increased significantly with decreasing the basal diameter, age and length of the branch, and with increasing the relative height of the branch. Among the branch traits, basal diameter was the best predictor for the NSC concentration of the old branch (the R2 between 0.87 and 0.95). The mean TNC contents of leaves, new branches, and old branches for the two species accounted for 28%, 2% and 70% of the crown TNC content, respectively. Considering the effect of the spatial variability in the estimation of NSC content, we recommend the sampling protocol that applies the NSC concentration of new twigs and old branches with a diameter of 3 cm to up-scale the crown NSC content as a simple and practical method. PMID- 26685587 TI - [Aboveground architecture and biomass distribution of Quercus variabilis]. AB - The aboveground architecture, biomass and its allocation, and the relationship between architecture and biomass of Quercus variabilis of different diameter classes in Shangluo, south slope of Qinling Mountains were researched. The results showed that differences existed in the aboveground architecture and biomass allocation of Q. variabilis of different diameter classes. With the increase of diameter class, tree height, DBH, and crown width increased gradually. The average decline rate of each diameter class increased firstly then decreased. Q. variabilis overall bifurcation ratio and stepwise bifurcation ratio increased then declined. The specific leaf areas of Q. variabilis of all different diameter classes at vertical direction were 0.02-0.03, and the larger values of leaf mass ratio, LAI and leaf area ratio at vertical direction in diameter level I , II, III appeared in the middle and upper trunk, while in diameter level IV, V, VI, they appeared in the central trunk, with the increase of diameter class, there appeared two peaks in vertical direction, which located in the lower and upper trunk. The trunk biomass accounted for 71.8%-88.4% of Q. variabilis aboveground biomass, while the branch biomass accounted for 5.8% 19.6%, and the leaf biomass accounted for 4.2%-8.6%. With the increase of diameter class, stem biomass proportion of Q. variabilis decreased firstly then increased, while the branch and leaf biomass proportion showed a trend that increased at first then decreased, and then increased again. The aboveground biomass of Q. variabilis was significantly positively correlated to tree height, DBH, crown width and stepwise bifurcation ratio (R2:1), and positively related to the overall bifurcation ratio and stepwise bifurcation ratio (R3:2), but there was no significant correlation. Trunk biomass and total biomass aboveground were negatively related to the trunk decline rate, while branch biomass and leaf biomass were positively related to trunk decline rate, but their correlations were all not significant. PMID- 26685588 TI - [Bacterial community structure and diversity in soils of different forest ages and types in Bao- tianman forest, Henan Province, China]. AB - To compare the microbial compositions and diversities in soils of different forest ages and types in Baotianman forest, Henan Province, China, genomic DNA of forest soils was extracted for amplifying the 16S rRNA V4 hyper variable region by PCR and sequencing by Illumina MiSeq. The BIPES, UCHIME and QIIME were employed to analyze the soil bacterial community. It was shown that 60 phyla were identified, with Proteobacteria, Acidobacteria, and Verrucomicrobia representing the most dominant lineages and accounting for 29%, 18.5% and 10% of all sequences, respectively. At the genus level, 1209 genera were identified, the most abundant phylotypes were DA101 (6.3%), Acidobacteria-2 (5.9%), Candidatus Solibacter (2.9%) and Candidatus Nitrososphaera (2.6%). Different forest age and type soil samples had unique compositions and specific high and rare genus. Forest type and age both impacted the soil microbial community structure, and the influence of the former was stronger than the latter. The soil microbial diversity of the 80-year-old Quercus aliena forest was the lowest among all age and type forest soil samples. Soil pH, soil nitrogen and organic carbon contents were the most important factors affecting soil bacterial community structure. PMID- 26685589 TI - [Characteristics of soil organic carbon and enzyme activities in soil aggregates under different vegetation zones on the Loess Plateau]. AB - In order to explore the distribution characteristics of organic carbon of different forms and the active enzymes in soil aggregates with different particle sizes, soil samples were chosen from forest zone, forest-grass zone and grass zone in the Yanhe watershed of Loess Plateau to study the content of organic carbon, easily oxidized carbon, and humus carbon, and the activities of cellulase, beta-D-glucosidase, sucrose, urease and peroxidase, as well as the relations between the soil aggregates carbon and its components with the active soil enzymes were also analyzed. It was showed that the content of organic carbon and its components were in order of forest zone > grass zone > forest-grass zone, and the contents of three forms of organic carbon were the highest in the diameter group of 0.25-2 mm. The content of organic carbon and its components, as well as the activities of soil enzymes were higher in the soil layer of 0-10 cm than those in the 10-20 cm soil layer of different vegetation zones. The activities of cellulase, beta-D-glucosidase, sucrose and urease were in order of forest zone > grass zone > forest-grass zone. The peroxidase activity was in order of forest zone > forest-grass zone > grass zone. The activities of various soil enzymes increased with the decreasing soil particle diameter in the three vegetation zones. The activities of cellulose, peroxidase, sucrose and urease had significant positive correlations with the contents of various forms of organic carbon in the soil aggregates. PMID- 26685590 TI - [Influence of nitrogen and phosphorus addition on the aboveground biomass in Inner Mongo- lia temperate steppe, China]. AB - The plants in arid environment are constrained not only by water availability, but also by soil nutrient conditions. In order to clarify to what extent nutrient addition would facilitate the growth of plants in semi-arid region, we conducted a nitrogen (N) and phosphorus (P) addition experiment in Inner Mongolia temperate grassland in 2012 and 2013. In our experiment, N was added at 10 and 40 g N . m( 2) . a(-1) alone or in combination with P addition (10 g P . m(-2) . a(-1)). N addition significantly improved plant aboveground biomass (AGB) during the two study years. AGB in the treatments of 10 and 40 g . m2 . a(-1) was enhanced by 50.8% and 65.9% in 2012, and 71.6% and 93.3% in 2013, respectively. However, no significant difference in AGB enhancement was found between two N addition treatments. Compared with N addition treatments at the rates of 10 and 40 g . m( 2) . a(-1), N plus P addition improved AGB by 98.4% and 186.8% in 2012, and 111.7% and 141.4% in 2013, respectively. N addition generally increased all the three main functional types (i.e., Gramineae, Asteraceae and others) , and the three functional types contributed nearly equally to the increase of the community AGB. In comparison, Asteraceae contributed largest to the increments of AGB under the N plus P addition treatments. Our results also indicated that N and P addition remarkably increased the ground coverage, resulting in improved surface soil moisture condition, which might be one important reason that N and P addition could facilitate plant growth in arid environment. PMID- 26685591 TI - [Microbial community structure of the alpine meadow under different grazing styles in Naqu prefecture of Tibet]. AB - To clarify the effects of grazing styles on the soil microbial community in the alpine meadow, we explored the changes of soil microbial community structure in the alpine meadow located in Naqu district of Tibet Autonomous Region by analyzing the soil chemical properties and phospholipid fatty acids (PLFAs). The results showed that the contents of soil total organic carbon, total phosphate and nitrate nitrogen under the different grazing styles followed the trend of 7 year rest grazing > free grazing > grazing prohibition. Except for the ratio of fungal PLFAs/bacterial PLFAs, total PLFAs, the bacterial PLFAs, the fungal PLFAs, the gram negative bacterial and the gram positive bacterial PLFAs over the different grazing types were in the order of 7-year rest grazing > 5-year grazing prohibition > 7-year and 9-year grazing prohibition. The principal component analysis (PCA) presented that the first principal component (PC1 = 74.6%) was mainly composed of monounsaturated fatty acids, polyunsaturated fatty acids and branched fatty acids, and the second principal component (PC2 = 13.2%) was mainly composed of saturated fatty acids and some monounsaturated fatty acids. Total PLFAs content was significantly positively correlated with microbial biomass carbon content. Compared with grazing prohibition, fallow grazing was best for the alpine meadow in Naqu district, and free grazing with light intensity was good for the alpine meadow. PMID- 26685592 TI - [Extraction of spectral difference characteristics of Stellera chamaejasme in Qilian County of Qinghai Province, Northwest China]. AB - Stellera chamaejasme is one of the main poisonous weeds distributed in alpine meadow of Qinghai Province. Rapid spreading of S. chamaejasme has done serious harm to local animal husbandry and caused continuous grassland ecosystem degradation. This paper focused on the spectral differences between S. chamaejasme and herbage, taking the typical degraded alpine meadow dominated by S. chamaejasme in Qilian County of Haibei Region as the test site and using the spectral measurements acquired in the full-blossom period of S. chamaejasme from 2012 to 2014. The results showed that the spectral behavior of flowers of S. chamaejasme differed significantly from green background that included leaves of S. chamaejasme and herbage within 350-900 nm of VIS-NIR wavebands. The biggest reflectance difference between flowers of S. chamaejasme and green background was located in the red valley, followed by the blue valley. The reflectance of S. chamaejasme community increased with the rising of coverage, the biggest reflectance difference between S. chamaejasme and herbage communities lied in the near-infrared peak, and the best separability between S. chamaejasme communities with different coverage was also at the point. The difference of first derivative spectra between flowers of S. chamaejasme and green background located in amplitude of yellow edge was remarkable, followed by amplitude of blue edge, the same as differences between S. chamaejasme and herbage communities. Linear regression analysis between coverage of S. chamaejasme and spectral feature parameters showed best result for red valley (R2 = 0.94). Finally, the red valley, the blue valley and the near-infrared peak were proposed for discriminating S. chamaejasme from herbage in the full-blossom period of S. chamaejasme, and the combination of corresponding red, blue and near-infrared bands could be used to build sensitive indices for S. chamaejasme recognition. PMID- 26685593 TI - [Effects of NO3- stress on photosynthetic characteristics and nitrogen metabolism of strawber- ry seedlings]. AB - In order to explore the effects of NO3- stress on photosynthetic characteristics and nitrogen metabolism, strawberry seedlings were grown in sand culture condition under different concentrations of NO3- (64, 112 and 160 mmol . L(-1)) with the control of 16 mmol NO3- . L(-1). The results indicated that at the 8th day after treatment, with the increased NO3- concentration, the strawberry leaf net photosynthetic rate (Pn), stomatal conductance (g(s)), PS II actual photochemical efficiency (PhiPS II), PS II maximum photochemical efficiency (Fv/Fm), and photochemical quenching coefficient (q(P)) significantly decreased, and decreased by 67.7%, 68.4%, 35.7%, 23.2% and 26.9%, respectively, when NO3- concentration reached 160 mmol . L(-1) compared with the control. The non photochemical quenching coefficient (q(N)) increased by 4.4%, 10.9% and 75.8% respectively in the treatments of 64, 112 and 160 mmol NO3- . L(-1) compared with the control. The intercellular CO2 concentration (Ci) decreased under low NO3- concentration stress and then increased under high NO3- concentration stress, while the stomatal limitation (Ls) was vice versa. With the increased NO3- concentration, the nitrate nitrogen, ammonia nitrogen, total nitrogen and Kjeldahl nitrogen contents in the strawberry leaves and roots increased, but the protein nitrogen content decreased. The activities of nitrate reductase (NR) , glutamine sybthetase (GS), glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) increased at low NO3- concentration and then decreased at high NO3 concentration. Consequently, the net photosynthetic rate of strawberry seedling leaves decreased, the PS II electron transfer was blocked, the nitrogen accumulated with the increasing NO3- concentration, and the nitrogen metabolism enzyme activity decreased at high NO3- concentrations. When the NO3- concentration reached 64 mmol . L(-1) or higher in the nutrient solution, the growth of strawberry seedlings were inhibited significantly. PMID- 26685594 TI - [Influence of dehydration and diurnal variation on characteristics of chlorophyll fluorescence of leaves in Haloxylon ammodendron and H. persicum]. AB - To evaluate the ecological adaptation mechanism of Haloxylon ammodendron and H. persicum from Ningxia, the host of Cistanche deserticola, the chlorophyll fluorescence under dehydration and diurnal variation was determined by IMAGING PAM method. The results showed that H. ammodendron had higher photosynthetic electron transport activity (Fv/Fm), photosynthetic efficiency (qP), and PS II electron transport activity (ETR) than H. persicum. After 48 h dehydration, the chlorophyll fluorescence and water-retaining property of H. ammodendron were significantly higher than those of H. persicum. The significant difference in diurnal variation between H. ammo- dendron and H. persicum was observed and a 'V' trend was exhibited. It suggested that H. ammodendron had a stronger ability to adapt to the environment and had wider distribution, while H. persicum was limited by water and light and had narrow distribution. PMID- 26685595 TI - [Effects of rotations and different green manure utilizations on crop yield and soil fertility]. AB - A 4-year field experiment was conducted to investigate the influence of three rotation systems and three corresponding leguminous green manure (LGM) application methods on wheat yield and soil properties. The rotation patterns were summer fallow--winter wheat (SW), LGM-- winter wheat (LW) and LGM--spring maize--winter wheat (LMW). The three LGM application methods of LW included: early mulch, early incorporation and late incorporation while the three LGM application methods of LMW were: stalk mulch, stalk incorporation and stalk move away. The results indicated that for LW, LGM consumed more soil water, thus the wheat yield was not stable. The nitrate storage in 0-200 cm soil after wheat harvest was significantly higher than that of the others, indicating an increasing risk of nitrate leaching. Early mulch under LW had the highest soil organic carbon (SOC) content and storage of SOC (SSOC) in 0-20 cm soil. For LMW, wheat yield was comparatively stable among years, because of higher water storage before wheat seeding, and the nitrate storage in 0-200 cm soil after wheat harvest was significantly lower than LW, which decreased the risk of nitrate leaching. Stalk mulch had higher SOC content in 0-20 cm soil after wheat harvest compared with move-away. In addition, compared with the soil when the experiment started, stalk much also increased SSOC in 0-20 cm soil. In conclusion, LMW with stalk mulch could increase soil water storage, stabilize crop yield, improve soil fertility and decrease 0-200 cm soil nitrate storage. This system could be treated as a good alternative for areas with similar climate. PMID- 26685596 TI - [Reactive nitrogen loss pathways and their effective factors in paddy field in southern China]. AB - Based on the literature data, the N20 emission, N leaching, N runoff and NH3 volatilization were compared from different rice production regions and their effective factors were evaluated. The results showed that N2 0 emission, N leaching and N runoff in single rice in Yangtze River basin were higher than in other rice production regions, with N loss of 1.89, 6.4 and 10.4 kg N . hm(-2), and N loss rate of 0.8%, 3.8% and 5.3%, respectively. The high N20 emission, N leaching and N runoff in these regions might be attributed to high-rate N application and dry-wet alternation. The NH3 volatilization was the highest in late rice in southern China, with N loss of 54.9 kg N . hm(-2) and N loss rate of 35.2% due to higher temperature at late rice growing stage. In the field, the practice often decreased one reactive N loss but increased another one, indicating that intergated practical management is necessary to reduce reactive N loss. Reactive N loss often increase with increasing grian yield, which is associed with the high-rate N application. The N20 emission, N leaching and N runoff decreased with increasing the partial factor productivity of applied N (PFP). Therefore, reducing N losses per unit of yield is necessary for integrating higher yield with minimum environmental pollution. PMID- 26685597 TI - [Index screening and comprehensive evaluation of phenotypic traits of low nitrogen tolerance using BILs population derived from Dongxiang wild rice (Oryza rufipogon Griff)]. AB - To identify the low nitrogen tolerance of Dongxiang wild rice (DXWR) and its progenies, ten phenotypic traits including plant height (PH), heading day (HD), panicle length (PL), number of effective tillers per plant (NETP), number of filled grains per panicle (NFGP), number of grains per panicle (NGP), grain density (GD), spikelet fertility (SF), 1000-grain mass (TGM) and grain yield per plant (GYP) were studied under normal and low nitrogen treatments, using backcross inbred lines (BILs) of Xieqingzao B//DXWR/Xieqingzao B in BC1 F12. Comprehensive evaluation on the low nitrogen tolerance of the BILs population was conducted using principal component analysis and the subordinate function. The evaluation results indicated that the low nitrogen tolerance of the line 116, 143 and 157 was the strongest, which could be served as the intermediate materials for genetic studies on the low nitrogen tolerance of DXWR and breeding for the low nitrogen tolerance in rice. The optimal regression equation of the low nitrogen tolerance in rice was established using stepwise regression analysis. The relative values of five traits including PH, NGP, SF, TGM and GYP were screened out and could be used as comprehensive evaluation indices for the low nitrogen tolerance in the whole growth stage. Therefore, more attention should be paid to the relative values of these five traits, especially for NGP and GYP, in the genetic improvement of the low nitrogen tolerance in rice. PMID- 26685598 TI - [Effects of supplemental irrigation by measuring moisture content in different soil layers on water consumption characteristics, photosynthesis and grain yield of winter wheat]. AB - Field experiments were conducted during 2012-2014 winter wheat growing seasons. Six irrigation treatments were designed: rainfed, W0; a local irrigation practice that irrigated at jointing and anthesis with 60 mm each time, W1; four irrigation treatments were designed with target relative soil moisture of 65% field capacity (FC) at jointing and 70% FC at anthesis in 0-20 (W2) 0-40 (W3), 0-60 (W4) , and 0 140 cm (W5) soil layers, respectively, to study the effects of supplemental irrigation by measuring moisture content in different soil layers on water consumption characteristics and photosynthesis and grain yield of winter wheat. The irrigation amounts at jointing in W1 and W4 were the highest, followed by W3 treatment, W2 and W5 were the lowest. The irrigation amounts at anthesis and total irrigation amounts were ranked as W5 > Wl, W4 > W3 > W2, the total water consumption in W3 was higher than that in W2, but had no difference with that in W1, W4 and W5 treatments, W3 had the higher soil water consumption than W1, W4 and W5 treatments, and the soil water consumption in 40-140 cm soil layers from jointing to anthesis and in 60-140 cm soil layers from anthesis to maturity in W3 were significantly higher than the other treatments. The photosynthetic rate, transpiration rate and water use efficiency of flag leaf at middle stage of grain filling from the W3 treatment were the highest, followed by the W1 and W4 treatments, and W0 treatment was the lowest. In the two growing seasons, the grain yield and water use efficiency in the W3 were 9077-9260 kg . hm(-2) and 20.7-20.9 kg . hm(-2) . mm(-1), respectively, which were higher than those from the other treatments, and the irrigation water productivity in the W3 was the highest. As far as high-yield and high-water use efficiency were concerned in this experiment, the most appropriate soil layer for measuring moisture content was 0-40 cm. PMID- 26685599 TI - [Effects of long-term mixed application of organic and inorganic fertilizers on canopy apparent photosynthesis and yield of winter wheat]. AB - A field experiment was conducted using the winter wheat (Triticum aestivum) variety Shimai 15. The source of organic nitrogen was cow manure, and four fertilization treatments were included, i.e., no N fertilizer application, single application of urea, single application of cow manure, and mixed application of urea and cow manure. The effects of different applications of inorganic and organic nitrogen on canopy apparent photosynthesis (CAP), photosynthetic rate of flag leaves (Pn), leaf area index (LAI), florescence parameters and grain yield of winter wheat were determined. The results showed that urea had the largest effect on the early growth period, as at this stage the CAP, Pn and LAI of the single application of urea were the highest, which was followed by the mixed application and the single application of cow manure. However, 10 days after anthesis, the single application of cow manure and the mixed application delayed the leaf senescence process when compared with the single application of urea. This could be due to the two treatments having higher anti-oxidant enzyme activity and promoting a longer green leaf duration, which could maintain a higher photosynthetic capability. What' s more, the mixed application had a better performance and got the highest grain yield. Consequently, the mixed application of organic and inorganic fertilizers could delay leaf senescence and maintain a better canopy structure and higher photosynthesis capability at the late grain filling stage, which resulted in a higher grain yield. PMID- 26685600 TI - [Estimation of sugar to nitrogen ratio in wheat leaves with near infrared spectrometry]. AB - The soluble sugar to nitrogen ratio reflects the coordination degree of carbon (C) and nitrogen (N) metabolism. Precise and real-time monitoring of soluble sugar to nitrogen ratio is of significant importance for nitrogen diagnosis and management regulation in wheat production. In this study, time-course near infrared spectroscopy and soluble sugar to nitrogen ratio of fresh and dry leaves were obtained under different field experiments with varied years and cultivar and N rates. The methods of partial least squares (PLS), back-propagation neural network (BPNN) and wavelet neural network (WNN) were used to develop the calibration models with the preprocessed spectra, respectively, and the dataset selected randomly was used to evaluate the constructed models. The results showed that the performance of the models for fresh-leaves was not satisfied, but good for dry-leaves with the root mean square errors of prediction (RMSEP) by PLS, BPNN and WNN models based on 1655-2378 nm less than 0.3% and with the coefficients of determination (R2) over than 0.9, respectively. In comparison, the model based on WNN was the best one. All these indicated that near infrared spectrometry could be applied to estimating the soluble sugar to nitrogen ratio in plant. The results provided the theoretical basis and technological approach for diagnosing crop C/N. PMID- 26685601 TI - [Effects of irrigation using dairy effluent on grain yield, phosphorus utilization and distribu- tion in soil profile in winter wheat-summer maize rotation system]. AB - Field experiments of winter wheat-summer maize rotation were conducted in North China Plain irrigation area to explore the effects of wheat season irrigation with dairy effluent on grain yield, phosphorus uptake, accumulative phosphorus usage efficiency and phosphorus accumulation in soil. The results showed that the irrigation with dairy effluent significantly improved the yields of winter wheat and summer maize. With the increasing of P2O5 carried by dairy effluent into soil, winter wheat yield increased at first and then decreased. When the P2O5 increased 137 kg . hm(-2), winter wheat yield increased to the maximum (7646.4 kg . hm(-2)) and the phosphorus utilization rate was the highest (24.8%). But excessive phosphorus decreased the winter wheat yield and phosphorus utilization efficiency. Summer maize yield and phosphorus uptake increased with the increase of P2O5 carried by dairy effluent. The summer maize yield increased by 2222.4 2628.6 kg . hm(-2) and the phosphorus uptake increased by 13.9-21.1 kg . hm(-2) in contrast to the control (CK). Under conventional phosphorus fertilization at 88 kg . hm(-2), and the summer maize yield increased by 2235.0 kg . hm(-2) compared with CK. As the time of irrigation with dairy effluent increasing, the grain yield increased more significantly. The cumulative phosphorus utilization in this rotation system increased year by year. After six seasons of crop harvest, the cumulative phosphorus utilization rate increased into 40.0%-47.7%. Under the experimental condition, two times of irrigation with the dairy effluents in the winter wheat-summer maize rotation system was the best operating mode. PMID- 26685602 TI - [Effects of long-term different fertilizations on biomass and nutrient content of maize root]. AB - Taking two long-term local field trials at the south edge of the Loess Plateau, which were found in 1990 and 2003, respectively, as test subjects, the effects of different fertilization practices on the maize root biomass and nutrient content were investigated in this paper. Maize roots in the 0-20 cm top soil post-maize harvest from the different fertilization practices were collected by hand in October 2011. The results showed that compared with control without fertilization and N, NK, or PK treatments, the NP, NPK, fertilizers plus manure (M1NPK and M2NPK) or plus straw return (SNPK) treatments significantly increased the dry mass of maize root. The C, N, P and K contents in maize roots in the NP, NPK, M1 NPK, M2NPK and SNPK treatments were also significantly higher than those of control, especially in the NPK plus organic manure treatments (M1 NPK and M2NPK) in the trial. Compared with the N fertilizer free treatment (N0), root biomass in the 120 kg N . hm(-2) (N120) and 240 kg N . hm(-2) ( N240) fertilization treatments increased by 38% and 45%, respectively, but there was no significant difference between N120 and N240 treatments. Nitrogen fertilizer application (N120 and N240) also improved the C, N, P and K contents in maize root. The water soluble organic C and total soluble N contents of maize root in the NP, NPK, M1NPK, M2NPK, SNPK and the N120 and N240 treatments were greater than those of control and other treatments. Otherwise, the cellulose and lignin contents in maize roots declined in the NPK, M1NPK, M2NPK, and SNPK treatments compared with other treatments. So the root C/N and lignin/N ratios in the control, PK and N0 treatments were significantly higher than those in the NP, NPK, M1NPK, M2NPK and SNPK treatments. We concluded that the optimum fertilization (e. g., NP, NPK, MNPK and SNPK treatments) could increase maize root growth and nutrient content and improve soil fertility and carbon sequestration through root residue into soil. PMID- 26685604 TI - [Effects of strong wind lodging at pre- and post-tasseling stages on growth and yield of summer maize]. AB - Surveying data for wind lodging disaster happening in Nanyang of Henan Province in August 1, 2013, were used to analyze the effects of strong wind lodging at pre and post-tasseling stages on growth and yield of summer maize, and to determine the differences in lodging resistance among varieties and the suitable sowing time for summer maize. The survey included two varieties of summer maize, Xundan 20 and Zhengdan 958, with five and three sowing dates, respectively. The lodging was divided into four types, i.e., root slope ( RS) , root lodging ( RL) , stem bending (SB) and stem broken (SBK). The results showed that wind lodging occurring at pre- and post-tasseling stages resulted in high lodging percentages for both varieties and all sowing dates. The lodging percentage of Xundan 20 variety ranged between 86.0% and 98.5% for five sowing dates. For Zhengdan 958 variety, it ranged between 60.0% and 76.4% for three sowing dates. After tasseling, the earlier the sowing date, the lower the lodging rate occurred. The main lodging types happening around the tasseling stage were RL with the lodging rate of 53.0%-84.3% for sowing dates II-V of Xundan 20. The main lodging type for sowing date I was SB with the lodging rate of 37.5%. Lodging reduced the aboveground dry matter with the greatest reduction rate occurring in SB, followed by RS and RL. Lodging increased the allocation of dry matter to leaves and stems, but decreased the allocation to spikes. RL and SB shortened the length and diameter of spike, and reduced the grain number per spike. The lodging occurring after the tasseling stage also reduced 100-grain mass. RS had no significant effects on spike characters and yield components. The lodging had serious effects on the yield of summer maize. The yield loss was highest for SB with the reduction percentages of 74.2% and 68.7% for Xundan 20 and Zhengdan 958, respectively. SB occurring before the tasseling stage would lead to a complete crop failure. RL decreased the average yield by 46.3% and 46.5% for Xundan 20 and Zhengdan 958, respectively. RS decreased the averaged yield by 8.4% and 13.2% for Xundan 20 and Zhengdan 958, respectively. The mean yields of Xundan 20 and Zhengdan 958 were 4959.9 and 6026.1 kg . hm(-2) after the wind lodging, respectively. The later the sowing date, the higher the yield loss rate was observed for Xundan 20, however, there were no significant difference in yield loss among different sowing dates of Zhengdan 958. In general, Zhengdan 958 had stronger lodging resistance than Xundan 20. PMID- 26685603 TI - [Effects of sowing depth on seedling traits and root characteristics of summer maize]. AB - Two summer maize hybrids, Zhengdan 958 (ZD958) and Xianyu 335 (XY335), were used as experimental materials. 4 sowing depths (3, 5, 7 and 9 cm) and uneven sowing depth (CK) were designed under sand culture and field experiments to investigate the effects of sowing depth on seedling traits and root characteristics of summer maize. The results showed that the seedling emergence rate gradually decreased and seedling emergence time gradually lengthened as the sowing depth increased. Compared with the sowing depth of 3 cm, the seedling emergence rates of ZD958 and XY335 sown at the depth of 9 cm were reduced by 9.4% and 11.8%, respectively, and the seedling emergence duration was prolonged 1.5 d. With the increasing sowing depth, the seedling length and uniformity decreased significantly, the mesocotyl length increased significantly, while the coleoptile length had no significant difference; the primary radicle length gradually decreased, the total length of secondary radicle gradually increased, and the total root length had no significant difference; the total dry mass of seedling and mesocotyl increased significantly, and the total root dry mass had no significant difference. With the increasing sowing depth, the soluble sugar content in each part of seedling increased and the amount of nutritional consumption of germinating seeds increased, the seedling root growth rate increased, but the root activity decreased, and the number of total nodal root and nodal layers increased. With the increasing sowing depth, harvested ears per unit area were reduced by decreased seedling emergence rate and seedling vigor, thus influenced the yield. In addition, uniform sowing depth could improve the canopy uniformity and relative characteristics, then increase the yield. PMID- 26685605 TI - [Effects of maize plant types on dry matter accumulation characteristics and yield of soybean in maize-soybean intercropping systems]. AB - In order to explore the effects of maize plant types on dry matter accumulation and yield of soybean, a field experiment was conducted in 2013, including three maize-soybean relay strip intercropping systems. The relay strip intercropping systems were designed as soybean (Gongxuan 1) intercropped with Denghai 605 (RI1), Chuandan 418 (RI2) or Yayu 13 ( RI3), and the monocultured soybean was used as control. The results demonstrated that the dry matter accumulation rates of intercropped soybean in RI2 and RI3 treatments were lower than in RI1 treatment, and the leaf, stem and pod dry matter accumulation of intercropped soybean in RI1 treatment was 17.6%, 16.5% and 13.7% higher than that in RI2 treatment, and 34.6%, 33.1% and 28.4% higher than that in RI3 treatment, respectively. The distribution proportion of leaf and stem of intercropped soybean was in the order of RI1 > RI2 > RI3. However, the trend of the distribution proportion of pod was opposite. Compared with RI2 and RI3, the dry matter translocation amount, translocation proportion, contribution proportion of soybean vegetative organs to pod of soybean were improved in RI, treatment, and the pod per plant, seeds per plant, seeds per pod, yield per plant and yield of soybean in RI, were higher than RI2 and RI3 by 6.8%, 11.5%, 4.4%, 15.9%, 15.6% and 14.3%, 22.2%, 6.7%, 33.4%, 36.8%, respectively. The results showed that the yield was positively related with the accumulation rate of dry matter, dry matter translocation, dry matter translocation ratio and the contribution of dry matter accumulation, and these indices were highest in RI treatment. The results indicated that the compact maize relay intercropped with soybean could effectively regulate the dry matter accumulation, translocation and distribution, and improve the yield of soybean. PMID- 26685606 TI - [Effects of corn and soybean straws returning on CO2 efflux at initial stage in black soil]. AB - In this study, the CO2 emission characteristics and its relationships with C and N concentration in soil amended with different types of residues were studied by thermostatic incubation method to investigate the decomposition characteristics of different types of residues after adding to the soil and the effect of C, N concentration in residues on carbon sequestration. The results showed that during 61 days incubation, the CO2 efflux rates in the soils added with the different residues changed over time and exhibited an initial decrease, followed by a stable low plateau, and then an increase to a high plateau and finally followed by a decrease. The characteristics of CO2 emissions varied with residues, with the differences mainly occurring in the starting and duration of the high plateau CO2 emission period. The cumulative CO2-C emission was significantly affected by residue type. The cumulative CO2-C emissions from soils amended with corn roots, bottom corn stalks, corn leaves, and soybean leaves (about 160 umol . g(-1) of soil and residue) were significantly greater than those from soils amended with other residues for the initial 21 days. Except for soybean leaves, the cumulative soil CO2 emissions over the 61 day incubation period from soils amended with soybean residues were higher than that from soil amended with corn residues. There were significant linear relationships between the ratio of cumulative CO2-C emission to residue carbon concentration (CR), and both C/N and nitrogen concentration of residues in the initial 21 days incubation, but not for the entire 61 days incubation. Our study suggested that soil CO2 emission was closely dependent upon the type of residue. Soybean residues decomposed more easily than corn residues. However, the decay rate of soybean residues was slower than that of corn residues at the initial stage of incubation. Soil CO2 emission was significantly affected by the C/N ratios and nitrogen concentrations of crop residues only at the early phase of incubation. PMID- 26685607 TI - [Key time window of fiber quality formation in response to short-term higher temperature stress]. AB - By taking two cotton cultivars with different temperature-sensitivity (Sumian 15, temperature-sensitive cultivar and Kemian 1, temperature-insensitive cultivar) as materials, an experiment with two temperature regimes (high temperature: 34 degrees C [38/30 degrees C], HT and control: 26 degrees C [30/22 degrees C], CK) were set in climate chamber to study the change of key matters in different genotypes cotton in response to high temperature and their relationships with fiber quality. The results showed that as treated in the 34.0 degrees C high temperature regime for 5 days at different DPA (days past anthesis), significant change in fiber quality was observed in the temperature-sensitive cultivar Sumian 15. The key time window for fiber length, fiber strength and Micronaire in response to the high temperature stress was from 0 to 18.3 DPA, 10.9 to 26.1 DPA, and 10.5 to 34.0 DPA, respectively. So, it could be concluded that the key time window of cotton fiber development in response to high temperature stress was around 11 to 18 DPA. After treated under high temperature stress at the key time window for 5 days, the content of sucrose decreased firstly then increased compared with that in the control, the content of callose increased and the content of cellulose decreased by 4.2% in maximum. The fiber length decreased (by 23.3% in maximum), fiber strength increased (by 4.3% in maximum), Micronaire decreased (by 10.5% in maximum) , and the general fiber quality deteriorated. Similar changes and trends were also observed in the temperature-insensitive cultivar Kemian 1 except that the variation degree was comparatively lower. PMID- 26685608 TI - [Effects of soil wetting pattern on the soil water-thermal environment and cotton root water consumption under mulched drip irrigation]. AB - Abstract: To explore the effects of soil wetting pattern on soil water-thermal environment and water consumption of cotton root under mulched drip irrigation, a field experiment with three drip intensities (1.69, 3.46 and 6.33 L . h(-1)), was carried out in Shihezi, Xinjiang Autonomous Region. The soil matric potential, soil temperature, cotton root distribution and water consumption were measured during the growing period of cotton. The results showed that the main factor influencing the soil temperature of cotton under plastic mulch was sunlight. There was no significant difference in the soil temperature and root water uptake under different treatments. The distribution of soil matrix suction in cotton root zone under plastic mulch was more homogeneous under ' wide and shallow' soil wetting pattern (W633). Under the 'wide and shallow' soil wetting pattern, the average difference of cotton root water consumption between inner row and outer row was 0.67 mm . d(-1), which was favorable to the cotton growing trimly at both inner and outer rows; for the 'narrow and deep' soil wetting pattern (W169), the same index was 0.88 mm . d(-1), which was unfavorable to cotton growing uniformly at both inner and outer rows. So, we should select the broad-shallow type soil wetting pattern in the design of drip irrigation under mulch. PMID- 26685609 TI - [Assessment and early warning of land ecological security in rapidly urbanizing coastal area: A case study of Caofeidian new district, Hebei, China]. AB - Assessment and early warning of land ecological security (LES) in rapidly urbanizing coastal area is an important issue to ensure sustainable land use and effective maintenance of land ecological security. In this study, an index system for the land ecological security of Caofeidian new district was established based on the Pressure-State-Response (P-S-R) model. Initial assessment units of 1 km x 1 km created with the remote sensing data and GIS methods were spatially interpolated to a fine pixel size of 30 m x 30 m, which were combined with the early warning method (using classification tree method) to evaluate the land ecological security of Caofeidian in 2005 and 2013. The early warning level was classed into four categories: security with degradation potential, sub-security with slow degradation, sub-security with rapid degradation, and insecurity. Result indicated that, from 2005 to 2013, the average LES of Caofeidian dropped from 0.55 to 0.52, indicating a degradation of land ecological security from medium security level to medium-low security level. The areas at the levels of insecurity with rapid degradation were mainly located in the rapid urbanization areas, illustrating that rapid expansion of urban construction land was the key factor to the deterioration of the regional land ecological security. Industrial District, Shilihai town and Nanpu saltern, in which the lands at the levels of insecurity and sub-security with rapid degradation or slow degradation accounted for 58.3%, 98.9% and 81.2% of their respective districts, were at the stage of high early warning. Thus, land ecological security regulation for these districts should be strengthened in near future. The study could provide a reference for land use planning and ecological protection of Caofeidian new district. PMID- 26685610 TI - [Scenario analysis on sustainable development of Sino-Singapore Tianjin Eco-city based on emergy and system dynamics]. AB - Dynamic evaluation of sustainable development is one of the key fundamental parts of the success of Sino-Singapore Tianjin Eco-city, which is the first eco-city in China constructed by international cooperation. Based on the analysis of nature and economy, function and structure, planning control indices and so on, we constructed a sustainable development evaluation index system and a system dynamics model of Sino-Singapore Tianjin Eco-city to explore dynamic trends of its population, material and currency by comprehensive utilization of emergy analysis and system dynamics method. Five scenarios were set up and simulated, including inertial scenario, scientific and technological scenario, economic scenario, environmental scenario and harmonious development scenario. Then, the sustainability of the 5 scenarios was evaluated and compared. The results showed that in the economy and environment sustainable development scenario, there was a steady growth trend of GDP, accumulation of both emergy and currency, and relatively lower values in emergy waste ratio, emergy ratio of waste, and emergy loading ratio. Although both sustainable evaluation indices, such as ESI and UEI, were relatively low, the economy and environment sustainable development scenario was still the best development scenario which was more active than others. PMID- 26685611 TI - [An ecological compensation standard based on water environmental capacity of Kouhe River, Liaoning Province, China]. AB - Kouhe River water pollution caused by industry, agriculture and life sewage, not only reduced the water use function, but also directly affected the quality of Qinghe River. Due to the lack of effective management of water resources, the irrational use and water environment pollution occurred in Kouhe River basin. In this paper, in order to maintain the sustainable development of Kouhe River basin, taking Xifeng County and Kaiyuan City as two control units, COD as pollution factor, the water environmental capacity of Kouhe River basin was calculated. Combined with water quality monitoring data, river environment functional zone, pollution census data and the recovery cost of COD, an ecological compensation standard was determined. When the guarantee rates were 50%, 75%, and the average flow of the driest month in recent 10 years, the corresponding compensation standards of Xifeng County to downstream Kaiyuan City were 390.9 x 10(4), 448.6 x 10(4) and 514 x 10(4) yuan . a(-1), respectively. The river basin ecological compensation mechanism was put forward which should include ecological compensation fund raising, allocation and supervision. PMID- 26685612 TI - [Level indicators construction and temporal-spatial distribution features of agricultural flood in the southwest of China]. AB - Flood level indicators of southwest provinces were built in this study by using daily precipitation data of 341 weather stations in southwest agricultural areas from 1961 to 2010 combined with grey correlation analysis. In the process of building the indicators, we took single station flood indicators of Chongqing as the prototype. Through increasing and decreasing the precipitation threshold of Chongqing indicators by the amplitude of -50-+50 mm and the step size of 1 mm, each province got 101 groups of flood indicators. Based on the correlation between flood intensity calculated by all the indicators and crop flood real seriousness, coincidence between indicators and historical flood records and the comparability of different province indicators, we finally constructed agricultural flood level indicators of each province step by step. According to the flood indicators, we also analyzed temporal-spatial distribution features of flood disaster in southwest agricultural areas. The results were as follows: the final indicators of Yunnan were the original indicators plus 16 mm, while it was plus 30 mm for Guizhou and plus 40 mm for Sichuan-Chongqing. The correlation coefficients between flood index defined by indicators and affected ratio were 0.314 (P < 0.05), 0.553 (P < 0.01) and 0.305 (P < 0.05), respectively. The coincidence was relatively high between indicators and historical flood records. The ages in which flood disaster appeared very serious were 1980s in Yunnan, 1990s in Guizhou and 1980s and 2000s in Sichuan-Chongqing in the nearly 50 years. In the southwest and southeast of Yunnan, southwest of Guizhou and west and northeast of Sichuan Basin, the flood disaster was prevalent. PMID- 26685613 TI - [Assessing environmental and economical benefits of integrated sewage treatment systems]. AB - Sewage treatment, treated water treatment and sludge treatment are three basic units of an integrated sewage treatment system. This work assessed the influence of reusing or discharge of treated water and sludge landfill or compost on the sustainability of an integrated sewage treatment system using emergy analysis and newly proposed emergy indicators. This system's value included its environmental benefits and the products. Environmental benefits were the differences of the environmental service values before and after sewage treatment. Due to unavailability of data of the exchanged substance and energy in the internal system, products' values were attained by newly proposed substitution values. The results showed that the combination of sewage treatment, treated water reuse and sludge landfill had the strongest competitiveness, while the combination of sewage treatment, treated water reuse and earthworm compost was the most sustainable. Moreover, treated water reuse and earthworm compost were helpful for improving the sustainability of the integrated sewage treatment system. The quality of treated water and local conditions should be also considered when implementing the treated water reuse or discharge. The resources efficiency of earthworm compost unit needed to be further improved. Improved emergy indices were more suitable for integrated sewage treatment systems. PMID- 26685614 TI - [Scale effect of Li-Xiang Railway construction impact on landscape pattern and its ecological risk]. AB - As a large corridor project, plateau railway has multiple points and passes various sensitive environments along the railway. The determination of the scope of impact on ecological environment from railway construction is often controversial in ecological impact assessment work. Taking the Tangbu-Jiantang section of Li-Xiang Railway as study object, and using present land use map (1:10000) in 2012 and DEM as data sources, corridor cutting degree index ( CCI) and cumulative effect index of corridor (CCEI) were established by topology, buffer zone and landscape metrics methods. Besides, the ecological risk index used for railway construction was improved. By quantitative analysis of characteristics of the spatio-temporal change of landscape pattern and its evolution style at different spatial scales before and after railway construction, the most appropriate evaluation scale of the railway was obtained. Then the characteristics of the spatio-temporal variation of ecological risk within this scale before and after railway construction were analyzed. The results indicated that the cutting model and degree of railway corridor to various landscape types could be effectively reflected by CCI, and the exposure and harm relations between risk sources and risk receptors of railway can be measured by CCEI. After the railway construction, the railway corridor would cause a great deal of middle cutting effect on the landscape along the railroad, which would influence wood land and grassland landscape most greatly, while would cause less effect of edge cutting and internal cutting. Landscape indices within the 600 m buffer zone demonstrated the most obvious scale effect, therefore, the 600 m zone of the railway was set as the most suitable range of ecological impact assessment. Before railway construction, the low ecological risk level covered the biggest part of the 600 m assessment zone. However, after the railway construction, the ecological risk increased significantly, and the most part of the study area was at the moderate ecological risk level. The ecological risk presented ring-shaped and multi-kernel patterns, and was lower in the southern part than in the northern part of the study area. PMID- 26685615 TI - [Identification of ecological corridors for Tibetan antelope and assessment of their human disturbances in the alpine desert of Qinghai-Tibet Plateau]. AB - The alpine desert of Qinghai-Tibet Plateau (QTP) provides the largest habitats for those endangered ungulates (e.g., Tibetan antelope, Tibetan Kiang and wild yak) on the earth. However, human disturbance especially infrastructure constructions (e.g., railway & highway) has increasingly fragmented the habitats of those endangered ungulates by disturbing and interrupting their ecological corridors for their seasonal migration. Aiming at identifying the potential ecological corridors for Tibetan antelope, a GIS-based model-Linkage Mapper was used to model and detect the potential ecological corridors of Tibetan antelope based on the principle of least cost path. Three categories of ecological corridors, i. e., closed (inside reserves), linking (linking the reserves) and open (starting from reserve but ending outside) corridors were distinguished by their spatial interactions with existing major national nature reserves (i.e., Altun, Kekexili and Qiangtang NNRs) in the alpine desert of QTP, and their spatial patterns, conservation status associated with human disturbance were also examined. Although our research indicated a general ecological integration of both habitats and ecological corridors in the alpine desert ecosystem, increasing human disturbance should not be ignored, which particularly partially undermined the functioning of those ecological corridors linking the nature reserves. Considering disadvantages of prevailing separate administrative structure of nature reserve on the effective conservation of ecological corridors for those endangered ungulates, a coordinative conservation network among these major national nature reserves should be established to ensure the unified trans boundary conservation efforts and to enhance its overall conservation efficacy by sharing information, knowledge and optimizing conservation resources. PMID- 26685616 TI - [Eupolyphaga frass and its extracts protected tomato from Meloidogyne incognita infestation]. AB - The control effects of Eupolyphaga (Eupolyphaga sinensis Walker) frass and its extracts on Meloidogyne incognita were studied through laboratory assays and pot experiments, and the organic volatile compounds and oligochitosan contents in the frass were analyzed. The results indicated that the nematode immobility and mortality was significantly increased with increasing the extract concentration and treatment time. Compared with the control, egg hatching was significantly inhibited when the extract concentration was beyond 20%. Pot experiment indicated that root galling of tomato seedlings was reduced and the relative control effect was significantly improved with the increasing frass application. Meanwhile, plant height, stem diameter and leaf number of tomato increased with the increasing dosage of eupolyphaga frass. The ingredients analysis showed that the content of oligochitosan was about 4.35% and there were 9 categories and 110 kinds of volatile compounds in the frass. PMID- 26685617 TI - [[Catch composition of monofilament gillnet netting with different mesh sizes in Qingcaosha Reservoir, Shanghai, China]. AB - During 2010 to 2012, fish diversity in Qingcaosha Reservoir was studied based on gillnets (multi-mesh monofilament gillnets and single-mesh trammel gillnets), electric fishing, bottom trawl and cage. The investigation collected a total of 34 fish species, belonging to 8 orders, 12 families. Cypriniformes contained the largest number of species (19 species) in the collection, followed by Perciformes (6 species). Multi-mesh monofilament gillnets sampled 19 fish species, of which Coilia nasus was the dominant species. Hierarchical cluster analysis indicated that mesh size of monofilament gillnets had significant influence on the composition of catches: C. nasus and Hemiculter bleekeri were the dominant species of catches of gillnet netting with mesh size of 2 cm, while C. nasus was the dominant species of catches of the nettings with mesh sizes larger than 2 cm. Species numbers and the catch per unit of effort ( CPUE) had a decreasing tendency with the increasing mesh size. Mesh size also had significant effects on the total length distribution of the dominant species C. nasus, which increased with the increasing mesh size. The results suggested that a combination of several gears was required to reliably estimate fish diversity of standing waters. PMID- 26685618 TI - [Long-term pattern of diatom community structure changes in response to multiple environmental stressors at Datun Lake, Southeast Yunnan, China]. AB - Subtropical plateau lakes in Southeast Yunnan are known to have experienced multiple environmental stressors (lake pollution, eutrophication, land reclamation and droughts) during the past decades. Here, we applied multi-proxy analyses (i.e., diatom, grain size, C and N isotopic and chronology) of lake sediments, aiming to track the history of lake environment change and the characteristics of diatom community responses in Datun Lake for the past century. The results proved that the sedimentary diatom community records showed significant changes with the replacement of Fragilaria construens by Achnanthes minutissima. Combining with multiple-proxy records (i.e., isotopic data) and modern monitoring records, the ordination analyses and variation partitioning further suggested that industrial pollution and eutrophication were the major driving factors that led to the long-term shift of diatom community. In addition, the grain size results and meteorological data revealed that the reductions in hydrodynamic and water exchange intensity associated with damming and the occurrence of extreme droughts, thus led to the corresponding diatom community change. PMID- 26685619 TI - [Community characteristics of crustacean zooplankton and its relationship with environmental factors in Suzhou Industrial Park, Jiangsu Province, China]. AB - The monthly sampling data from June 2012 to May 2013 were used to study the composition and structure of the crustacean zooplankton community in the lakes and rivers of Suzhou Industrial Park. The variations in density and biomass of the crustacean zooplankton and their relationship with the environment factors were investigated. The results showed that a total of 42 species of crustacean zooplankton were found, including 24 species of cladocerans which belonged to 6 families and 12 genera, and 18 copepods which belonged to 7 families and 13 genera. The dominant species were Diaphanosoma brachyurum, Bosmina longirostris, Sinocalanus dorrii and Cyclops vicinus in all seasons of the year both in the rivers and the lakes. The density and biomass of the crustacean zooplankton in summer and autumn were higher than that in winter and spring, and there were two peaks in summer and autumn respectively both in the lakes and the rivers. The average density and biomass of cladocerans in the rivers were significantly higher than that in the lakes. There was no significant difference in the average density of Copepods between the rivers and the lakes, but the biomass in the rivers was higher than that in the lakes significantly. There were significant differences in dissolved oxygen, pH, Secchi depth, total dissolved solids, salinity, total phosphorus, total nitrogen and ammonium nitrogen between the lakes and the rivers. Redundancy analysis showed that the distribution of most of crustacean zooplankton was positively correlated with water temperature, the salinity, COD(Mn) and total phosphorus concentrations and only the distribution of the species belonging to genus Daphnia and Scapholeberis was positively correlated with O2 concentration, pH, and Secchi depth in both the rivers and the lakes in Suzhou Industrial Park. PMID- 26685620 TI - [Effects of environmental factors on beta diversity of zooplankton community in thermal discharge seawaters near Guohua Power Plant in Xiangshan Bay, Zhejiang, China]. AB - Zooplankton samples were seasonally collected at 10 stations in thermal discharge seawaters near Guohua Power Plant in Xiangshan Bay. The abundance data from these samples were pooled and further combined with field environmental factors, then generalised dissimilarity modelling (GDM) was used to explore the effects of environmental factors on beta diversity of zooplankton community. The results showed that altogether 95 species of zooplankton belonging to 14 taxa were found. In these taxa, small zooplankton with 62.6% of abundance was the main taxa, while copepods dominated in adult groups, which abundance accounted for 35.3%. According to Whittaker's definition and additive partition, a diversity accounted for 36.3% and beta diversity 63.7%. Environmental factors explained 43.8% of beta diversity, and geographical distance between sampling sites had no effect on beta diversity. However, there were still 19.9% of beta diversity remained to be explained. After GDM fitting, there were nine environmental variables affecting zooplankton beta diversity and explaining 68.8% of beta diversity. The variables contributing to beta diversity from high to low were seasonal water temperature, dissolved oxygen, seawater temperature increment, conductivity, suspended particulate matter, salinity, transparency, water depth and redox potential, respectively. Seasonal water temperature, dissolved oxygen and seawater temperature increment were the most important factors for driving beta diversity changes, and accounted for 23.9%, 13.7% and 9.7% of absolute contribution to the interpretable portion of the beta diversity, respectively. When seasonal water temperature, dissolved oxygen and seawater temperature increment were below 25 degrees C, greater than 5 mg . L(-1) and over 1 degrees C, respectively, beta diversity rapidly increased with the increasing variable gradients. Furthermore, other predictors had little effect on beta diversity. PMID- 26685621 TI - [Construction and evaluation of an engineered bacterial strain for producing lipopeptide under anoxic conditions]. AB - Biosurfactant-facilitated oil recovery is one of the most important aspects of microbial enhanced oil recovery (MEOR). However, the biosurfactant production by biosurfactant-producing microorganisms, most of which are aerobes, is severely suppressed due to the in-situ anoxic conditions within oil reservoirs. In this research, we successfully engineered a strain JD-3, which could grow rapidly and produce lipopeptide under anoxic conditions, by protoplast confusion using a Bacillus amyloliquefaciens strain BQ-2 which produces biosurfactant aerobically, and a facultative anaerobic Pseudomonas stutzeri strain DQ-1 as parent strains. The alignment of 16S rDNA sequence (99% similarity) and comparisons of cell colony morphology showed that fusant JD-3 was closer to the parental strain B. amyloliquefaciens BQ-2. The surface tension of culture broth of fusant JD-3, after 36-hour cultivation under anaerobic conditions, decreased from initially 63.0 to 32.5 mN . m(-1). The results of thin layer chromatography and infrared spectrum analysis demonstrated that the biosurfactant produced by JD-3 was lipopeptide. The surface-active lipopeptide had a low critical micelle concentration (CMC) of 90 mg . L(-1) and presented a good ability to emulsify various hydrocarbons such as crude oil, liquid paraffin, and kerosene. Strain JD 3 could utilize peptone as nitrogen source and sucrose, glucose, glycerin or other common organics as carbon sources for anaerobic lipopeptide synthesis. The subculture of fusant JD-3 showed a stable lipopeptide-producing ability even after ten serial passages. All these results indicated that fusant JD-3 holds a great potential to microbially enhance oil recovery under anoxic conditions. PMID- 26685622 TI - [Heat-responsive mechanisms in plants revealed by proteomic analysis: A review]. AB - Heat stress is a major abiotic stress that limits plant growth and productivity. In recent years, proteomic investigations provide more information for understanding the sophisticated heat-responsive molecular mechanism in plants at systematic biological level. The heat-responsive proteomic patterns in several plants, i. e., model plants (Arabidopsis thaliana), staple food crops (soybean, rice and wheat), heat-tolerant plants (Agrostis stolonifera, Portulaca oleracea, and Carissa spinarum), grapevine, Populus euphratica, Medicago sativa, and Pinellia ternate, were reported. A total of 838 heat-responsive proteins have been identified in these studies. Among them, 534 proteins were induced and the expression of 304 proteins was reduced in plants under heat stress. In this paper, the diverse protein patterns in plants under various heat stress conditions (30-45 degrees C for 0-10 d) were analyzed integratively. This provided new evidences and clues for further interpreting the signaling and metabolic pathways, e.g., signaling, stress and defense, carbohydrate and energy metabolism, photosynthesis, transcription, protein synthesis and fate, membrane and transport, in heat-responsive networks, and laid a foundation for a holistic understanding of the molecular regulatory mechanism in plants in response to heat stress. PMID- 26685623 TI - [Discussion on agricultural product quality and safety problem from ecological view]. AB - There are many different perspectives about the sustainable agriculture, which had been proposed since the last three decades in the world. While China's ecologists and agronomists proposed a similar concept named 'ecological agriculture'. Although ecological agriculture in China has achieved substantial progress, including theory, models and supporting technologies nearly several decades of practice and development, its application guidance still is not yet clear. The organic agriculture model proposed by European Union is popular, but it is limited in the beneficiary groups and the social and ecological responsibility. In this context, the article based on an ecological point of view, analyzed the shortcomings of ecological imbalance caused by a single mode of agricultural production and the negative impact on the quality of agricultural products, and discussed the core values of ecological agriculture. On this basis, we put forward the concept of sustainable security of agricultural products. Based on this concept, an agricultural platform was established under the healthy ecosysphere environment, and from this agricultural platform, agricultural products could be safely and sustainably obtained. Around the central value of the concept, we designed the agricultural sustainable and security production model. Finally, we compared the responsibility, benefiting groups, agronomic practices selection and other aspects of sustainable agriculture with organic agriculture, and proved the advancement of sustainable agricultural model in agricultural production quality and safety. PMID- 26685624 TI - [A review of green roof performance towards management of roof runoff]. AB - Green roof has a significant influence on reducing runoff volume, delaying runoff yielding time, reducing the peak flow and improving runoff quality. This paper addressed the related research around the world and concluded from several aspects, i.e., the definition of green roof of different types, the mechanism how green roof manages runoff quantity and quality, the ability how green roof controls roof runoff, and the influence factors of green roof toward runoff quantity and quality. Afterwards, there was a need for more future work on research of green roof toward roof runoff, i.e., vegetation selection of green roof, efficient construction model selection of green roof, the regulating characteristics of green roof on roof runoff, the value assessment of green roof on roof runoff, analysis of source-sink function of green roof on the water pollutants of roof runoff and the research on the mitigation measures of roof runoff pollution. This paper provided a guideline to develop green roofs aiming to regulating roof runoff. PMID- 26685625 TI - Restraint of an Agitated Patient. An EMT's rapport is key when an elderly patient becomes upset. PMID- 26685626 TI - Practice What You Preach. Mistakes happen--don't let anger shape your reaction to them. PMID- 26685627 TI - How to Start an injury Prevention Program. Better techniques and stretching can reduce employee injuries. PMID- 26685628 TI - Steps to Designing a Safety Management System. Being proactive and predictive, instead of reactive, is key to success. PMID- 26685629 TI - The International Roots of Community Paramedicine. What we can learn from programs in Australia and Canada. PMID- 26685630 TI - EVIDENCE-BASED EMS: Automated Chest Compression Devices. Does the evidence demonstrate a true benefit to ACCDs with cardiac arrest victims? PMID- 26685631 TI - SEARCH and RESCUE ON THE BORDER. The elite BORSTAR search and rescue team provides care for all in need. PMID- 26685632 TI - Disparate Measures. What's the best way to evaluate performance and help workers improve? PMID- 26685633 TI - SELF-DIRECTED LEARNING, TEAMWORK, HOLISTIC VIEW AND ORAL HEALTH. AB - The dental program at the Malmo Dental School, the so called Malmo-model, is guided by four linked principles: self-directed learning, teamwork, a holistic view of patient care, and oral health (Fig.1). Self-assessment ability is a critical competence for healthcare professionals, necessary for the successful adaptation to the modern life-long learning environment. Educational research seems to point out two critical factors for the development of such skills, continuous practice of self-assessment and constructive feedback. The first study presented in this thesis assessed students' self-assessment ability by means of the Interactive Examination in a cohort of senior dental students, who had gone through an identical assessment procedure during their second year of studies. The results indicated that self-assessment ability was not directly relevant to subject knowledge. Upon graduation, there were a number of students (10%) with significant self-assessment difficulties. Early detection of students with weak self-assessment abilities appears possible to achieve. The aim of the second study, concerning teamwork and holistic view, was to investigate if highlighting teamwork between dental and dental hygienist students could improve the students' holistic view on patients, as well as their knowledge of, and insight into, each other's future professions. This project showed that by initiating teamwork between dental and dental hygienist students, it was possible to increase students' knowledge on dental hygienists competence, develop students' perceived holistic view on patients, and prepare students for teamwork. The third study explored findings clinicians used when diagnosing chronic periodontitis. A questionnaire was distributed to students, dental teachers and clinical supervisors in the Public Dental Services. Within all categories of clinicians, the majority of the clinicians used deepened pocket, bone loss on x-rays, and bleeding as findings. There were differences in the use of findings between the categories of clinicians. None of the supervisors used attachment loss as a finding, while 13% to 27% of the other categories of clinicians used this finding. A higher frequency of dental hygienist students used plaque, calculus and pus, compared to the other categories. Dental hygienist students used more findings for diagnosing as compared to the other categories of clinicians. Fifty eight of the 76 clinicians used each finding solitarily, i.e. one at a time, and not in combination to diagnose chronic periodontitis. However, about a third of the dental students and the supervisors only used findings either from the soft tissue inflammation subgroup or the loss of supporting tissue subgroup. With the exception of the dental teachers, the majority of clinicians within each category used irrelevant findings. The third study gave valuable information when designing the fourth study. In the fourth study, a questionnaire was distributed to 2,455 professional clinicians, i.e. dentists and dental hygienists in public and private activity, and dental students at the Dental School in Malmo. The results showed that two groups, representing dentists and dental hygienists delivering basic periodontal care in Sweden, were to a significant degree not sharing the knowledge basis for diagnosis and treatment planning. This may result in a less optimal utilization of resources in Swedish dentistry. The delivery of basic periodontal care was not in line with the severity of disease and too much attention was paid to the needs of relatively healthy persons. To change this pattern, the incentives in, and structure of, the national assurance system need to be adapted in order to stimulate a better inter-collegial cooperation between dentists and dental hygienists in basic periodontal care. PMID- 26685634 TI - ORTHODONTIC RETENTION. Studies of retention capacity, cost-effectiveness and long term stability. AB - Retention strategies, cost-effectiveness and long-term stability of treatment outcome are essential aspects of orthodontic treatment planning. The overall aim of this thesis was to compare and evaluate three different retention strategies, with special reference to short- and long-term clinical stability and cost effectiveness. The approach was evidence-based, hence randomized controlled methodology was used in order to generate high levels of evidence. This thesis is based on four studies: Papers I and II are based on randomized controlled trials, evaluating the stability of treatment outcome after one and two years of retention, using three different retention strategies: a maxillary vacuum-formed retainer combined with a mandibular canine-to-canine retainer; a maxillary vacuum formed retainer combined with stripping of the mandibular anterior teeth and a prefabricated positioner. Paper III presents a cost-minimization analysis of two years of retention treatment. Paper IV is based on a randomized controlled trial documenting the results five years post-retention. The following conclusions were drawn: Papers I and II. From a clinical perspective, asssessment after one year of retention disclosed that the three retention methods were successful in retaining the orthodontic treatment results. After two years of retention, all three retention methods were equally effective in controlling relapse at a clinically acceptable level. Most of the relapse occurred during the first year of retention; only minor or negligible changes were found during the second year. The subjects were grouped according to the level of compliance (excellent or good). After two years of retention there was a negative correlation between growth in body height and relapse of mandibular LII in the group of subjects with excellent compliance. The group with good compliance showed a positive correlation (Paper II, Figure 3). After two years of retention, growth in body height, initial crowding and gender had no significant influence on mandibular LII (Paper II, Figure 4 and Table 4). Paper III. The cost minimization analysis disclosed that although the three retention methods achieved clinically similar results, the associated societal costs differed. After two years of retention, the vacuum-formed retainer (VFR) in combination with a canine-to-canine retainer (CTC) was the least cost-effective retention appliance. Paper IV. After five years or more out of retention, the three retention methods had achieved equally favourable clinical results. Key conclusion and clinical implications. This study compared the short- and long-term outcomes of orthodontic retention by three different methods: a maxillary vacuum-formed retainer combined with a mandibular canine-to-canine retainer; a maxillary vacuum-formed retainer combined with stripping of the mandibular anterior teeth and a prefabricated positioner. All methods gave equally positive clinical results in both the short-term, i.e. after one and two years of retention, and in the long-term, five years or more post retention. After two years of retention, the level of compliance affected the retention treatment result. However, no such effect was shown for body height, the severity of initial crowding or gender. Today, there is increasing emphasis on the importance of economic aspects of healthcare. Of the three methods evaluated in this study, the least cost-effective, after two years of retention, was a vacuum-formed retainer combined with a bonded canine-to-canine retainer. The clinical implication of this finding is that in patients meeting the inclusion criteria, interproximal stripping of the mandibular anterior teeth, or the use of a prefabricated positioner, are highly appropriate alternatives to a mandibular bonded canine-to-canine retainer. The overall conclusions are that there are a number of effective retention methods available and the clinician is not limited to routine use of a bonded mandibular canine-to-canine retainer. The most appropriate retention method should be selected on an individual, case to case basis, taking into account such variables as orthodontic diagnosis, the expected level of patient compliance, patient preferences and financial considerations. PMID- 26685636 TI - Coming up with a concrete solution. PMID- 26685635 TI - The right steps for safe work at height. PMID- 26685638 TI - Tools' significant role in supportive design. PMID- 26685637 TI - London Trusts proud to describe their work. AB - 'Waste not, Want not' was the title of a recent IHEEM seminar which examined some of the key issues for those responsible for dealing with healthcare waste--from regulatory compliance and correct segregation of waste streams, to the opportunities for more on-site processing. HEJ editor, Jonathan Baillie, reports on the joint presentations given by key environmental and sustainability personnel at two of London's largest NHS Trusts, and their private sector waste management partners. These discussed some of the key initiatives that each Trust and its 'partner' have taken to not only significantly reduce the amount of waste generated on their estate, but also to dispose of it in an environmentally responsible way. These initiatives, the speakers explained, were all part of their organisations' journey on the road to achieving 'Deep Green', a 'nirvana' like state where their activities have a zero net impact on the environment. PMID- 26685639 TI - A collaborative project from start to finish. PMID- 26685640 TI - Natural ventilation with low costs. PMID- 26685641 TI - Consider whether your estate may be too big. PMID- 26685642 TI - Are your consultants up to the task? PMID- 26685643 TI - Processing on site can cut costs. PMID- 26685644 TI - Innovative solutions, bespoke expertise. PMID- 26685645 TI - Are closed systems a 'closed book'? PMID- 26685646 TI - [When too much information kills communication!]. PMID- 26685647 TI - [Social networks and medicine]. AB - Social networks (social media or #SoMe) have entered medical practice within the last few years. These new media--like Twitter or Skype--enrich interactions among physicians (telemedicine), among physicians and patients (virtual consultations) and change the way of teaching medicine. They also entail new ethical, deontological and legal issues: the extension of the consultation area beyond the medical office and the access of information by third parties were recently debated. We develop here a review of some social networks with their characteristics, applications for medicine and limitations, and we offer some recommendations of good practice. PMID- 26685648 TI - [Taking into account spiritual dimension of the patient in multidisciplinary team]. AB - In the current healthcare environment, there is an increasing consensus for a holistic approach to the patient by means of a bio-psychosocial and spiritual model. The first part of this article describes how, in the context of a laic healthcare environment, physicians, nurses and spiritual caregivers are asked to change their way to communicate and to take into account this spiritual dimension. In the second part we will discuss some of the challenges of this interdisciplinary approach of the spiritual dimension in the hospital and the community. We will describe potential benefits for the patients, their family members and the caregivers. At the end, taking into account the spiritual dimension of the patient without proselytism will depend on the capacity of each caregiver to speak about it and to share this information in multidisciplinary team. PMID- 26685649 TI - [Effective communication strategies to frame the trainer-trainee dialogue in the clinical setting]. AB - Communication between trainer and trainee plays a central role in teaching and learning in the clinical environment. There are various strategies to frame the dialogue between trainee and trainer. These strategies allow trainers to be more effective in their supervision, which is important in our busy clinical environment. Communication strategies are well adapted to both in- and out patient settings, to both under- and postgraduate contexts. This article presents three strategies that we think are particularly useful. They are meant to give feedback, to ask questions and to present a case. PMID- 26685650 TI - [Discharge from hospital: how to improve continuity of medical care?]. AB - Early readmission is the major success indicator of the transition between hospital and home. Patients admitted with heart failure reach a 20% rate. Potentially avoidable readmissions, defined as unpredictable and related to a known condition during index hospitalization, represent the improvement margin. For these latter, implementation of specific interventions can be effective. Complex interventions on transition, including several modalities and seeking to encourage patient autonomy seem more effective than others. We describe two models: a pragmatic one developed in a regional hospital, and a more complex one developed in a university hospital during the LEAR-HF study. In both cases, it is imperative to work on "medical liability": should it extend beyond discharge up to the threshold of the private practice? PMID- 26685651 TI - [Delivering bad news in a Swiss internal medicine ward: a medical and nurse partnership]. AB - Delivering bad news to a patient has a major impact for patients, their relatives and caregivers. The way this information is delivered can affect the way the patient sees his disease and potentially how he adheres to its treatment. To improve this communication with the patient the service of internal medicine at the Swiss university hospital of Lausanne set up a process including the coordination between all involved caregivers, and to break the bad news in a setting including a medical and nurse partnership. It also underscores that the resident in charge of the patient remains the coordinator of delivering new information. Moreover, the service provides communication tools to the caregivers to improve the communication skills. PMID- 26685652 TI - [Incident-reporting electronic-based system in internal medicine]. AB - How to recognize, announce and analyze incidents in internal medicine units is a daily challenge that is taught to all hospital staff. It allows suggesting useful improvements for patients, as well as for the medical department and the institution. Here is presented the assessment made in the CHUV internal medicine department one year after the beginning of the institutional procedure which promotes an open process regarding communication and risk management. The department of internal medicine underlines the importance of feedback to the reporters, ensures the staff of regular follow-up concerning the measures being taken and offers to external reporters such as general practioners the possibility of using this reporting system too. PMID- 26685653 TI - [Good risk/benefit profile of treatment with confirmed alpha emitter]. PMID- 26685654 TI - [Radium dichloride-223 improves symptoms including in the daily clinic]. PMID- 26685656 TI - [Dying at home]. PMID- 26685655 TI - [Consumption of meat and cancer: how to keep right?]. PMID- 26685657 TI - [Education: practice of vaginal examinations (and/or rectal) without consent?]. PMID- 26685658 TI - [Tobacco and diabetes: another good reason to not smoke (or to stop)]. PMID- 26685659 TI - [Meat and public health]. PMID- 26685660 TI - [The role of screens on the deregulation of the internal clock of adolescents (2)]. PMID- 26685661 TI - [Plan of reorganization of hospitals in North Vaudois]. PMID- 26685662 TI - [According to WHO, processed meat is carcinogenic]. PMID- 26685663 TI - [Carcinogenic meat: buzz, populism and science]. PMID- 26685664 TI - Left ventricular fluid kinetic energy time curves in heart failure from cardiovascular magnetic resonance 4D flow data. AB - BACKGROUND: Measurement of intracardiac kinetic energy (KE) provides new insights into cardiac hemodynamics and may improve assessment and understanding of heart failure. We therefore aimed to investigate left ventricular (LV) KE time curves in patients with heart failure and in controls. METHODS: Patients with heart failure (n = 29, NYHA class I-IV) and controls (n = 12) underwent cardiovascular magnetic resonance (CMR) including 4D flow. The vortex-ring boundary was computed using Lagrangian coherent structures. The LV endocardium and vortex-ring were manually delineated and KE was calculated as 1/2mv(2) of the blood within the whole LV and the vortex ring, respectively. RESULTS: The systolic average KE was higher in patients compared to controls (2.2 +/- 1.4 mJ vs 1.6 +/- 0.6 mJ, p = 0.048), but lower when indexing to EDV (6.3 +/- 2.2 MUJ/ml vs 8.0 +/- 2.1 MUJ/ml, p = 0.025). No difference was seen in diastolic average KE (3.2 +/- 2.3 mJ vs 2.0 +/- 0.8 mJ, p = 0.13) even when indexing to EDV (9.0 +/- 4.4 MUJ/ml vs 10.2 +/- 3.3 MUJ/ml, p = 0.41). In patients, a smaller fraction of diastolic average KE was observed inside the vortex ring compared to controls (72 +/- 6% vs 54 +/- 9%, p < 0.0001). Three distinctive KE time curves were seen in patients which were markedly different from findings in controls, and with a moderate agreement between KE time curve patterns and degree of diastolic dysfunction (Cohen's kappa = 0.49), but unrelated to NYHA classification (p = 0.12), or 6-minute walk test (p = 0.72). CONCLUSION: Patients with heart failure exhibit higher systolic average KE compared to controls, suggesting altered intracardiac blood flow. The different KE time curves seen in patients may represent a conceptually new approach for heart failure classification. PMID- 26685665 TI - Development of a rapid, low-cost protoplast transfection system for switchgrass (Panicum virgatum L.). AB - KEY MESSAGE: A switchgrass protoplast system was developed, achieving a cost reduction of ~1000-fold, a threefold increase in transformation efficiency, and a fourfold reduction in required DNA quantity compared to previous methods. In recent years, there has been a resurgence in the use of protoplast systems for rapid screening of gene silencing and genome-editing targets for siRNA, miRNA, and CRISPR technologies. In the case of switchgrass (Panicum virgatum L.), to achieve economic feasibility for biofuel production, it is necessary to develop plants with decreased cell wall recalcitrance to reduce processing costs. To achieve this goal, transgenic plants have been generated with altered cell wall chemistry; however, with limited success owing to the complexity of cell walls. Because of the considerable cost, time, and effort required to screen transgenic plants, a protoplast system that can provide data at an early stage has potential to eliminate low performing candidate genes/targets prior to the creation of transgenic plants. Despite the advantages of protoplast systems, protoplast isolation in switchgrass has proven costly, requiring expensive lab-grade enzymes and high DNA quantities. In this paper, we describe a low-cost protoplast isolation system using a mesophyll culture approach and a cell suspension culture. Results from this work show a cost reduction of ~1000-fold compared to previous methods of protoplast isolation in switchgrass, with a cost of $0.003 (USD) per reaction for mesophyll protoplasts and $0.018 for axenic cell culture derived protoplasts. Further, the efficiency of protoplast transformation was optimized threefold over previous methods, despite a fourfold reduction in DNA quantity. The methods developed in this work remove the cost barrier previously limiting high-throughput screening of genome-editing and gene silencing targets in switchgrass, paving the way for more efficient development of transgenic plants. PMID- 26685666 TI - BRITTLE SHEATH1 encoding OsCYP96B4 is involved in secondary cell wall formation in rice. AB - KEY MESSAGE: Mutation of BSH1 leads to brittle sheath phenotype and reduction of very-long-chain fatty acids and their derivatives in wax. The cell wall plays an important role in plant mechanical strength. Several brittle culm mutants have been identified and characterized in rice. Here, we characterized an anther culture-derived rice brittle sheath mutant, named bsh1 and isolated BSH1 via map based strategy. BSH1 encodes OsCYP96B4 protein, which was localized on ER membrane in the protoplast transient assay. BSH1 is mainly expressed in developing vascular tissues and the cells in which cell wall secondary thickening is occurring. Mutation in bsh1 causes changes in cell wall composition by affecting the expression of cell wall-related genes. Moreover, bsh1 shows reduced amounts of very-long-chain fatty acids and their derivatives in wax rather than the medium-chain fatty acids. In summary, BSH1 functions mainly in secondary cell wall formation, and probably in wax biosynthesis in an unidentified mechanism. PMID- 26685667 TI - Clinical effectiveness and safety outcomes associated with prothrombin complex concentrates. AB - Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of warfarin and used for reversal of novel oral anticoagulants, in patients with acute major bleeding or need for an urgent procedure. The research goal was to evaluate effectiveness and safety outcomes with PCC usage at our institution. A retrospective review of electronic medical records identified patients that received a PCC commercially available in the United States (KCentra((r)) or Profilnine((r))) at twelve hospitals in a tertiary care health system from July 1, 2013 to April 30, 2014. A total of 193 patients received PCC, of which 184 patients received four-factor PCC. The patient population was 48 % male and 75 % Caucasian, with a mean age of 73 years old. Clinical outcomes of interest included time to achieve a target INR <=1.3, time to Hgb >7 g/dL, and incidence of thromboembolism. A total of 143 patients were on warfarin (74.1 %) at baseline, whereas 18 patients (9.3 %) were taking a novel anticoagulant. Target INR of <=1.3 was achieved in 125 patients (65.8 %), within a median time of 8.03 h (IQR 3.38-34.07). Among patients with a baseline Hgb <7 g/L (n = 13), the median time to Hgb >7 g/dL was 8.48 h (IQR 6.95-13.00). Eight patients (4.1 %) developed an acute venous thromboembolism following PCC administration. INR reversal was achieved in approximately two-thirds of patients, with a low incidence of venous thromboembolism. Four-factor PCC is a viable alternative to plasma. PMID- 26685669 TI - Commentary to: Metabolic engineering of Escherichia coli: construction of an efficient biocatalyst for D-mannitol formation in a whole-cell biotransformation. PMID- 26685668 TI - The Association of Neighborhood Gene-Environment Susceptibility with Cortisol and Blood Pressure in African-American Adults. AB - BACKGROUND: African-American adults are disproportionately affected by stress related chronic conditions like high blood pressure (BP), and both environmental stress and genetic risk may play a role in its development. PURPOSE: This study tested whether the dual risk of low neighborhood socioeconomic status (SES) and glucocorticoid genetic sensitivity interacted to predict waking cortisol and BP. METHODS: Cross-sectional waking cortisol and BP were collected from 208 African American adults who were participating in a follow-up visit as part of the Positive Action for Today's Health trial. Three single-nucleotide polymorphisms were genotyped, salivary cortisol samples were collected, and neighborhood SES was calculated using 2010 Census data. RESULTS: The sample was mostly female (65 %), with weight classified as overweight or obese (M BMI = 32.74, SD = 8.88) and a mean age of 55.64 (SD = 15.21). The gene-by-neighborhood SES interaction predicted cortisol (B = 0.235, p = .001, r (2) = .036), but not BP. For adults with high genetic sensitivity, waking cortisol was lower with lower SES but higher with higher SES (B = 0.87). Lower neighborhood SES was also related to higher systolic BP (B = -0.794, p = .028). CONCLUSIONS: Findings demonstrated an interaction whereby African-American adults with high genetic sensitivity had high levels of waking cortisol with higher neighborhood SES, and low levels with lower neighborhood SES. This moderation effect is consistent with a differential susceptibility gene-environment pattern, rather than a dual-risk pattern. These findings contribute to a growing body of evidence that demonstrates the importance of investigating complex gene-environment relations in order to better understand stress-related health disparities. PMID- 26685670 TI - Significance of wood extractives for wood bonding. AB - Wood contains primary extractives, which are present in all woods, and secondary extractives, which are confined in certain wood species. Extractives in wood play a major role in wood-bonding processes, as they can contribute to or determine the bonding relevant properties of wood such as acidity and wettability. Therefore, extractives play an immanent role in bonding of wood chips and wood fibres with common synthetic adhesives such as urea-formaldehyde-resins (UF resins) and phenol-formaldehyde-resins (PF-resins). Extractives of high acidity accelerate the curing of acid curing UF-resins and decelerate bonding with alkaline hardening PF-resins. Water-soluble extractives like free sugars are detrimental for bonding of wood with cement. Polyphenolic extractives (tannins) can be used as a binder in the wood-based industry. Additionally, extractives in wood can react with formaldehyde and reduce the formaldehyde emission of wood based panels. Moreover, some wood extractives are volatile organic compounds (VOC) and insofar also relevant to the emission of VOC from wood and wood-based panels. PMID- 26685671 TI - Simultaneous denitrification and phosphorus removal by Agrobacterium sp. LAD9 under varying oxygen concentration. AB - Although efficient aerobic denitrification has received increasing attention, few studies have been made on simultaneous denitrification and phosphorus removal (SDPR) under aerobic condition. In this study, SDPR by an efficient aerobic denitrifier, Agrobacterium sp. LAD9, was firstly demonstrated. High nitrate and phosphorus removal rates of 7.50 and 1.02 mg L(-1) h(-1) were achieved in wide range of O2 concentration from 5.92 to 20.02 mg L(-1). The N2O production would be inhibited as O2 concentration exceeded 11.06 mg L(-1), while the phosphorus removal efficiency would be generally improved with increasing O2 concentration. (15)N mass spectrometry revealed that nitrogen removal accorded with the typical aerobic denitrification pathway, while (31)P nuclear magnetic resonance spectroscopy ((31)P NMR) indicated the fate of phosphorus to cells, extracellular polymeric substances (EPS), and polyphosphate (poly-P) of the denitrifier. EPS acted as a reservoir of phosphorus and the transformation of poly-P was dynamic and depended on initial orthophosphate (ortho-P) content. The aerobic SDPR would greatly simplify the conventional wastewater treatment processes which required separated considerations of nitrogen and phosphorus removal. PMID- 26685672 TI - Influence of fermentation conditions on polysaccharide production and the activities of enzymes involved in the polysaccharide synthesis of Cordyceps militaris. AB - The influence of different fermentation conditions on intracellular polysaccharide (IPS) production and activities of the phosphoglucomutase (PGM), UDPG-pyrophosphorylase (UGP), phosphoglucose isomerase (PGI), UDPG-dehydrogenase (UGD), and glucokinase (GK) implicated in metabolite synthesis in Cordyceps militaris was evaluated. The highest IPS production (327.57 +/- 6.27 mg/100 mL) was obtained when the strain was grown in the optimal medium containing glucose (40 g . L(-1)), beef extract (10 g . L(-1)), and CaCO3 (0.5 g . L(-1)), and the initial pH and temperature were 7 and 25 degrees C, respectively. The activities of PGM, UGP, and PGI were proved to be influenced by the fermentation conditions. A strong correlation between the activities of these enzymes and the production of IPS was found. The transcription level of the pgm gene (encoding PGM) was 1.049 times and 1.467 times compared to the ugp gene and pgi gene (encoding UGP and PGI), respectively, in the optimal culture medium. This result indicated that PGM might be the highly key enzyme to regulate the biosynthesis of IPS of C. militaris in a liquid-submerged culture. Our study might be helpful for further research on the pathway of polysaccharide biosynthesis aimed to improve the IPS production of C. militaris. PMID- 26685674 TI - Lactobacillus and Leuconostoc volatilomes in cheese conditions. AB - New strains are desirable to diversify flavour of fermented dairy products. The objective of this study was to evaluate the potential of Leuconostoc spp. and Lactobacillus spp. in the production of aroma compounds by metabolic fingerprints of volatiles. Eighteen strains, including five Lactobacillus species (Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus sakei) and three Leuconostoc species (Leuconostoc citreum, Leuconostoc lactis, and Leuconostoc mesenteroides) were incubated for 5 weeks in a curd-based slurry medium under conditions mimicking cheese ripening. Populations were enumerated and volatile compounds were analysed by headspace trap gas chromatography-mass spectrometry (GC-MS). A metabolomics approach followed by multivariate statistical analysis was applied for data processing and analysis. In total, 12 alcohols, 10 aldehydes, 7 esters, 11 ketones, 5 acids and 2 sulphur compounds were identified. Very large differences in concentration of volatile compounds between the highest producing strains and the control medium were observed in particular for diacetyl, 2-butanol, ethyl acetate, 3-methylbutanol, 3-methylbutanoic acid and 2-methylbutanoic acid. Some of the characterized strains demonstrated an interesting aromatizing potential to be used as adjunct culture. PMID- 26685673 TI - EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice. AB - Optical reporter genes such as green fluorescent protein (GFP) and luciferase are efficiently and widely used in monitoring and studying the protective/therapeutic potential of candidate agents in leishmaniasis. But several observations and controversial reports have generated a main concern, whether enhanced GFP (EGFP) affects immune response. To address this issue, we studied the immunogenicity of EGFP in vivo by two lines of stably transfected parasites (Leishmania major (EGFP) or L. major (EGFP-LUC)) in BALB/c model and/or as a recombinant protein (rEGFP) produced in vitro by bacteria in parallel. Disease progression was followed by footpad swelling measurements and parasite burden in draining lymph nodes using microtitration assay and real-time PCR, and immune responses were also evaluated in spleen. EGFP-expressing parasites generated larger swellings in comparison with wild-type (L. major) while mice immunized with rEGFP and challenged with wild-type parasite were quite comparable in footpad swelling with control group without significant difference. However, both conventional and molecular approaches revealed no significant difference in parasite load between different groups. More importantly, no significant inflammatory responses were detected in groups with higher swelling size measured by interferon-gamma (IFN gamma), interleukin (IL)-10, IL-5, and nitric oxide against frozen and thawed lysate of parasite as stimulator. Altogether, these results clearly revealed that EGFP protein expressed in prokaryotic and eukaryotic hosts is not an immunological reactive molecule and acts as a neutral protein without any side effects in mice. So, EGFP expressing Leishmania could be a safe and reliable substitution for wild-types that simplifies in situ follow-up and eliminates the animal scarification wherever needed during the study. PMID- 26685675 TI - Characterisation of the genes involved in the biosynthesis and attachment of the aminodeoxysugar D-forosamine in the auricin gene cluster of Streptomyces aureofaciens CCM3239. AB - We previously identified the aur1 gene cluster which produces the angucycline antibiotic auricin. Preliminary characterisation of auricin revealed that it is modified by a single aminodeoxysugar, D-forosamine. Here we characterise the D forosamine-specific genes. The four close tandem genes, aur1TQSV, encoding enzymes involved in the initial steps of the deoxysugar biosynthesis, were located on a large operon with other core auricin biosynthetic genes. Deleting these genes resulted in the absence of auricin and the production of deglycosylated auricin intermediates. The two final D-forosamine biosynthetic genes, sa59, an NDP-hexose aminotransferase, and sa52, an NDP-aminohexose N dimethyltransferase, are located in a region rather distant from the core auricin genes. A deletion analysis of these genes confirmed their role in D-forosamine biosynthesis. The Deltasa59 mutant had a phenotype similar to that of the cluster deletion mutant, while the Deltasa52 mutant produced an auricin with a demethylated D-forosamine. Although auricin contains a single deoxyhexose, two glycosyltransferase genes were found to participate in the attachment of D forosamine to the auricin aglycon. An analysis of the expression of the D forosamine biosynthesis genes revealed that the initial D-forosamine biosynthetic genes aur1TQSV are regulated together with the other auricin core genes by the aur1Ap promoter under the control of the auricin-specific activator Aur1P. The expression of the other D-forosamine genes, however, is governed by promoters differentially dependent upon the two SARP family auricin-specific activators Aur1PR3 and Aur1PR4. These promoters contain direct repeats similar to the SARP consensus sequence and are involved in the interaction with both regulators. PMID- 26685676 TI - Shiga toxins: from structure and mechanism to applications. AB - Shiga toxins are a group of type 2 ribosome-inactivating proteins (RIPs) produced in several types of bacteria. The toxins possess an AB5 structure, which comprises a catalytic A chain with N-glycosidase activity, and five identical B chains and recognize and bind to the target cells with specific carbohydrate moieties. In humans, the major molecular target which recognizes the Shiga toxins is the Gb3 receptor, which is mainly expressed on the cell surface of endothelial cells of the intestine, kidney, and the brain. This causes these organs to be susceptible to the toxicity of Shiga toxins. When a person is infected by Shiga toxin-producing bacteria, the toxin is produced in the gut, translocated to the circulatory system, and carried to the target cells. Toxicity of the toxin causes inflammatory responses and severe cell damages in the intestine, kidneys, and brain, bringing about the hemolytic uremic syndrome (HUS), which can be fatal. The Shiga toxin requires a couple of steps to exert its toxicity to the target cells. After binding with the target cell surface receptor, the toxin requires a complicated process to be transported into the cytosol of the cell before it can approach the ribosomes. The mechanisms for the interactions of the toxin with the cells are described in this review. The consequences of the toxin on the cells are also discussed. It gives an overview of the steps for the toxin to be produced and transported, expression of catalytic activity, and the effects of the toxin on the target cells, as well as effects on the human body. PMID- 26685677 TI - Optimized production of HIV-1 virus-like particles by transient transfection in CAP-T cells. AB - HIV-1 virus-like particles (VLPs) have great potential as new-generation vaccines. The novel CAP-T cell line is used for the first time to produce Gag-GFP HIV-1 VLPs by means of polyethylenimine (PEI)-mediated transient transfection. CAP-T cells are adapted to grow to high cell densities in serum-free medium, and are able to express complex recombinant proteins with human post-translational modifications. Furthermore, this cell line is easily transfected with PEI, which offers the flexibility to rapidly generate and screen a number of candidates in preclinical studies. Transient transfection optimization of CAP-T cells has been performed systematically in this work. It is determined that for optimal production, cells need to be growing at mid-exponential phase, Protein Expression Medium (PEM) medium has to be added post-transfection, and cells can be transfected by independent addition of DNA and PEI with no prior complexation. A Box-Behnken experimental design is used to optimize cell density at time of transfection, DNA/cell and PEI/cell ratios. The optimal conditions determined are transfection at a density of 3.3E + 06 cells/mL with 0.5 pg of DNA/cell and 3 pg of PEI/cell. Using the optimized protocol, 6 * 10(10) VLP/mL are obtained, demonstrating that CAP-T is a highly efficient cell line for the production of HIV-1 VLPs and potentially other complex viral-based biotherapeutics. PMID- 26685678 TI - Vitrification of in vitro matured oocytes diminishes embryo development potential before but not after embryo genomic activation. AB - PURPOSE: The aim of this study is to evaluate the impact of oocyte vitrification on embryo development potential and to assess the chromosome abnormalities of blastocysts derived from fresh/vitrified-warmed oocytes to assure the safety of the oocyte cryopreservation technique. METHODS: In vitro matured oocytes derived from immature oocytes were retrieved from small follicles during IVF/intracytoplasmic sperm injection (ICSI) cycles were randomly divided into a fresh and vitrified-warmed groups. After intracytoplasmic sperm injection, the fertilization rate, embryo quality, and developmental status were compared between the two groups. Blastocysts derived from both groups were analyzed using the copy number variation (CNV)-seq technique to evaluate DNA abnormalities. RESULTS: The fertilization rate with ICSI and the cleavage rate were similar between the two groups. Among the vitrified-warmed group, there was a lower incidence of usable embryos on day 3 (16.42 vs. 28.57 %; P < 0.05) and a lower incidence of blastocysts (7.46 vs. 17.86 %; P < 0.05). However, the proportions of embryos that developed to blastocysts from the day 3 available embryos were similar between the two groups (62.5 vs. 45.45 %; P > 0.05). In the day 3 embryos, the proportion of >5 cell embryos in the fresh group was markedly higher than in the vitrified-warmed group (41.67 vs. 21.64 %; P < 0.05), and the proportion of embryos with ?50 % fragments was not significantly different between the two groups (39.29 vs. 43.28 %; P > 0.05). The result of CNV-seq demonstrated that there was no difference in chromosomal abnormalities between the two groups (20 vs. 20 %). CONCLUSIONS: Oocyte vitrification and the warming procedure diminished the embryo development potential before day 3, when embryo genomic activation started. The day 3 usable embryos derived from vitrified warmed oocytes had the same potential for developing into blastocysts. Vitrification and the warming procedure did not increase the chromosome abnormalities of the blastocysts. Oocyte vitrification is a safe technique for those patients who have no other options, although the oocyte efficiency may be diminished after the vitrified-warmed procedure. PMID- 26685680 TI - mQTL-seq delineates functionally relevant candidate gene harbouring a major QTL regulating pod number in chickpea. AB - The present study used a whole-genome, NGS resequencing-based mQTL-seq (multiple QTL-seq) strategy in two inter-specific mapping populations (Pusa 1103 * ILWC 46 and Pusa 256 * ILWC 46) to scan the major genomic region(s) underlying QTL(s) governing pod number trait in chickpea. Essentially, the whole-genome resequencing of low and high pod number-containing parental accessions and homozygous individuals (constituting bulks) from each of these two mapping populations discovered >8 million high-quality homozygous SNPs with respect to the reference kabuli chickpea. The functional significance of the physically mapped SNPs was apparent from the identified 2,264 non-synonymous and 23,550 regulatory SNPs, with 8-10% of these SNPs-carrying genes corresponding to transcription factors and disease resistance-related proteins. The utilization of these mined SNPs in Delta (SNP index)-led QTL-seq analysis and their correlation between two mapping populations based on mQTL-seq, narrowed down two (Caq(a)PN4.1: 867.8 kb and Caq(a)PN4.2: 1.8 Mb) major genomic regions harbouring robust pod number QTLs into the high-resolution short QTL intervals (Caq(b)PN4.1: 637.5 kb and Caq(b)PN4.2: 1.28 Mb) on chickpea chromosome 4. The integration of mQTL-seq-derived one novel robust QTL with QTL region-specific association analysis delineated the regulatory (C/T) and coding (C/A) SNPs-containing one pentatricopeptide repeat (PPR) gene at a major QTL region regulating pod number in chickpea. This target gene exhibited anther, mature pollen and pod-specific expression, including pronounced higher up-regulated (~3.5-folds) transcript expression in high pod number-containing parental accessions and homozygous individuals of two mapping populations especially during pollen and pod development. The proposed mQTL-seq-driven combinatorial strategy has profound efficacy in rapid genome-wide scanning of potential candidate gene(s) underlying trait-associated high-resolution robust QTL(s), thereby expediting genomics assisted breeding and genetic enhancement of crop plants, including chickpea. PMID- 26685679 TI - Salivary acinic cell carcinoma: reappraisal and update. AB - Epidemiologic and clinicopathologic features, therapeutic strategies, and prognosis for acinic cell carcinoma of the major and minor salivary glands are critically reviewed. We explore histopathologic, histochemical, electron microscopic and immunohistochemical aspects and discuss histologic grading, histogenesis, animal models, and genetic events. In the context of possible diagnostic difficulties, the relationship to mammary analog secretory carcinoma is probed and a classification is suggested. Areas of controversy or uncertainty, which may benefit from further investigations, are also highlighted. PMID- 26685682 TI - Erratum to: Structure and stability of the molybdenum cofactor intermediate cyclic pyranopterin monophosphate. PMID- 26685683 TI - Factors influencing length of hospital stay after primary total knee arthroplasty in a fast-track setting. AB - PURPOSE: The goal of this study was to identify factors prior to surgery that are associated with an increased length of hospital stay after TKA using a fast-track protocol. MATERIALS AND METHODS: In total, 879 consecutive patients who underwent primary TKA were included in this retrospective cohort study. A length of stay greater than or equal to three nights was considered an increased length of hospital stay. Univariable and multivariable generalized linear mixed models were used to identify potential factors associated with increased length of hospital stay. RESULTS: Length of hospital stay was significantly associated with age [OR 1.01 (95 % CI 1.01-1.02); p < 0.001], gender [female vs. male, OR 1.07 (95 % CI 1.00-1.15); p = 0.04], ASA [ASA III/IV vs. ASA I, OR 1.22 (95 % CI 1.06-1.39); p = 0.005], living situation (alone vs. together, OR 1.08 (95 % CI 1.00-1.16); p = 0.04], neurological comorbidities [OR 1.14 (95 % CI 1.06-1.23); p < 0.001], musculoskeletal comorbidities [OR 0.91 (95 % CI 0.85-0.97); p = 0.005], anaesthesia [spinal vs. general, OR 0.86 (95 % CI 0.76-0.97); p = 0.02], and weekday of surgery [Thursday vs. Monday, OR 1.12 (95 % CI 1.02-1.23); p = 0.02]. CONCLUSIONS: Older age, female gender, ASA III/IV, people living alone, the presence of neurological comorbidities, general anaesthesia and surgery on Thursday were associated with an increased length of hospital stay. In clinical practice, the knowledge of factors associated with an increased length of hospital stay can be used to further optimize peri-operative protocols for patients at risk for an increased length of hospital stay after TKA. LEVEL OF EVIDENCE: II. PMID- 26685684 TI - Histological analysis of the tibial anterior cruciate ligament insertion. AB - PURPOSE: This study was performed to investigate the morphology of the tibial anterior cruciate ligament (ACL) by histological assessment. METHODS: The native (undissected) tibial ACL insertion of six fresh-frozen cadaveric knees was cut into four sagittal sections parallel to the long axis of the medial tibial spine. For histological evaluation, the slices were stained with haematoxylin and eosin, Safranin O and Russell-Movat pentachrome. All slices were digitalized and analysed at a magnification of 20*. RESULTS: The anterior tibial ACL insertion was bordered by a bony anterior ridge. The most medial ACL fibres inserted from the medial tibial spine and were adjacent to the articular cartilage of the medial tibial plateau. Parts of the bony insertions of the anterior and posterior horns of the lateral meniscus were in close contact with the lateral part of the tibial ACL insertion. A small fat pad was located just posterior to the functional ACL fibres. The anterior-posterior length of the medial ACL insertion was an average of 10.8 +/- 1.1 mm compared with the lateral, which was only 6.2 +/- 1.1 mm (p < 0.001). There were no central or posterolateral inserting ACL fibres. CONCLUSIONS: The shape of the bony tibial ACL insertion was 'duck-foot like'. In contrast to previous findings, the functional mid-substance fibres arose from the most posterior part of the 'duck-foot' in a flat and 'c-shaped' way. The most anterior part of the tibial ACL insertion was bordered by a bony anterior ridge and the most medial by the medial tibial spine. No posterolateral fibres nor ACL bundles have been found histologically. This histological investigation may improve our understanding of the tibial ACL insertion and may provide important information for anatomical ACL reconstruction. PMID- 26685685 TI - Patient kinesiophobia affects both recovery time and final outcome after total knee arthroplasty. AB - PURPOSE: To evaluate the effects of kinesiophobia on both phases immediately after surgery and the final results after total knee arthroplasty (TKA). METHODS: This study evaluated prospectively 101 patients (mean age 66 +/- 8.0 years, 70 women and 31 men), 5 days after surgery, at 1, 6, 12 months, and at a mean final follow-up of 3.2 +/- 0.7 years (2.0-4.2 years). Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK: Activity Avoidance-TSK1 and Harm-TSK2 subscales), and results were evaluated with range of motion, pain and function on 0-10 numeric rating scales, WOMAC and SF-12 (Physical and Mental subscales) scores. RESULTS: TSK1 was correlated with the acute postoperative pain measured at 5 days (p = 0.031), pain measured at 12 months (p = 0.018), patient perceived function at 12 months (p = 0.025), SF-12P at 6 months (p < 0.001), SF-12P and SF 12M at 12 months (p = 0.001 and p = 0.005, respectively), and WOMAC at both 6 and 12 months of follow-up (p = 0.005 and p = 0.001). The effect of TSK 1 on the final WOMAC score was significant when corrected by age and sex (p = 0.049, eta 2 = 0.041): the youngest female patients were affected even by moderate kinesiophobia levels. CONCLUSIONS: Fear of pain and even more avoidance of movement are strongly correlated both with the acute postoperative pain perception and recovery after surgery up to 1 year, thus presenting a relevant clinical impact on the outcome after TKA. Moreover, this study showed that even though at longer follow-up its impact decreases, patients with higher levels of kinesiophobia may present a poorer final outcome, especially women. LEVEL OF EVIDENCE: IV. PMID- 26685686 TI - Can Bassett's ligament be removed? AB - PURPOSE: To investigate the functional characteristics of Bassett's ligament in the ankle, focusing on mechanoreceptors and potential problems following resection of Bassett's ligament. METHODS: Bassett's ligament, the anterior talofibular ligament (ATFL), and synovium were obtained from 20 ankles of 10 fresh-frozen cadavers. Histologically, mechanoreceptors were identified and classified as Ruffini (type I), Vater-Pacini (type II), Golgi-Mazzoni (type III) corpuscles, and free nerve endings (type IV). Differences in receptor densities were compared. RESULTS: Type I clusters were observed with three to six ramifications; type II mechanoreceptors were encapsulated in clusters of two to four with ovoid or cylindrical shape; type III were amorphous, long and wide, and fusiform- or spindle-shaped; and type IV were long and fine without a defined shape. Differences in the densities of the mechanoreceptors inside three soft tissues (Bassett's ligament, ATFL, and synovium) were not significant. CONCLUSION: There were no significant differences in the densities of the four types of mechanoreceptors among the soft tissues studied. In Bassett's ligament, type I mechanoreceptors were present at significantly higher densities than the other receptors. PMID- 26685681 TI - Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. AB - The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS. PMID- 26685687 TI - Impingement following anterior cruciate ligament reconstruction: comparing the direct versus indirect femoral tunnel position. AB - PURPOSE: During anterior cruciate ligament (ACL) reconstruction, authors have suggested inserting the femoral tunnel at the biomechanically relevant direct fibres, but this higher position can cause more impingement. Therefore, we aimed to assess ACL graft impingement at the femoral notch for ACL reconstruction at both the direct and indirect tunnel positions. METHODS: A virtual model was created for twelve cadaveric knees with computed tomography scanning in which a virtual graft was placed at direct and indirect tunnel positions of the anteromedial bundle (AM), posterolateral bundle (PL) or centre of the both bundles (C). In these six tunnel positions, the volume (mm3) and mid-point location of impingement ( degrees ) were measured at different flexion angles. RESULTS: Generally, more impingement was seen with the indirect position compared with the direct position although this was only significant at 90 degrees of flexion for the AM position (97 +/- 28 vs. 76 +/- 20 mm3, respectively; p = 0.046). The direct tunnel position impinged higher at the notch, whereas the indirect position impinged more towards the lateral wall, but this was only significant at 90 degrees of flexion for the AM (24 +/- 5 degrees vs. 34 +/- 4 degrees , respectively; p < 0.001) and C position (34 +/- 5 degrees vs. 42 +/- 5 degrees , respectively; p = 0.003). CONCLUSION: In this cadaveric study, the direct tunnel position did not cause more impingement than the indirect tunnel position. Based on these results, graft impingement is not a limitation to reconstruct the femoral tunnel at the insertion of the biomechanically more relevant direct fibres. PMID- 26685688 TI - Acromioclavicular joint dislocations: coracoclavicular reconstruction with and without additional direct acromioclavicular repair. AB - PURPOSE: To evaluate different stabilisation techniques for acromioclavicular (AC) joint separations, including direct AC repair, and to compare the properties of the stabilised and native joints. METHODS: An established in vitro testing model for the AC joint was used to analyse joint stability after surgical reconstruction [double TightRope (DTR), DTR with AC repair (DTR + AC), single TR with AC repair (TR + AC), and PDS sling with AC repair (PDS + AC)]. Twenty-four human cadaveric shoulders were randomised by age into four testing groups. Joint stiffness was measured by applying an axial load during defined physiological ranges of motion. Similar tests were performed for the native joints, after dissecting the coracoclavicular and AC ligaments, and after surgical reconstruction. Cyclic loading was performed for 1000 cycles with 20-70 N and vertical load to failure determined after cyclic testing. RESULTS: Axial stiffness for all TR groups was significantly higher than for the native joint (DTR 38.94 N/mm, p = 0.005; DTR + AC 37.79 N/mm, p = 0.015; TR + AC 45.61 N/mm, p < 0.001 vs. native 26.05 N/mm). The axial stiffness of the PDS + AC group was similar to that of the native joint group (21.4 N/mm, n.s.). AC repair did not significantly influence rotational stiffness. Load to failure was similar and >600 N in all groups (n.s.). CONCLUSION: Reconstruction of AC dislocations with one or two TRs leads to stable results with a higher stiffness than the native joints. For the PDS + AC group, axial stiffness was similar to the native situation, although there might be a risk of elongation. Direct AC repair showed no significantly increased stability in comparison with reconstructions without direct AC repair. Thus, a direct AC repair seems to be dispensable in clinical practice, while TRs or PDS cerclages appear to provide sufficiently stable results. PMID- 26685689 TI - Return to sports after arthroscopic capsulolabral repair using knotless suture anchors for anterior shoulder instability in soccer players: minimum 5-year follow-up study. AB - PURPOSE: To report the return to sports and recurrence rates in competitive soccer players after arthroscopic capsulolabral repair using knotless suture anchors at a minimum of 5 years of follow-up. METHODS: All competitive soccer players with anterior glenohumeral instability treated by arthroscopic capsulolabral repair using knotless suture anchors between 2002 and 2009 were retrospectively identified through the medical records. Inclusion criteria were: no previous surgical treatment of the involved shoulder, absence of glenoid or tuberosity fractures, absence of large Hill-Sachs or glenoid bone defect, minimum follow-up of 5 years, instability during soccer practice or games, and failure of non-surgical treatment. The charts of included players were reviewed, and a phone call was performed in a cross-sectional manner to obtain information on: current soccer, return to soccer, recurrence of instability, shoulder function (Rowe score), and disability [Quick-Disability of the Arm, Shoulder, and Hand (DASH) score and Quick-DASH Sports/Performing Arts Module]. RESULTS: Fifty-seven young male soccer players were finally included with a median (range) follow-up of 8 (5 10) years. Forty-nine (86 %) of the soccer players were able to return to soccer and 36 of them (73 %) at the same pre-injury level. There were 6 (10.5 %) re dislocations in the 57 players, all of them of traumatic origin produced during soccer and other unrelated activities. The main reasons to not return to soccer were: knee injuries (two players), changes in personal life (two players), and job-related (three players). None of the players quit playing soccer because of their shoulder instability injury. The median (range) Rowe score, Quick-DASH score, and Quick-DASH sports score were 80 (25-100), 2.3 (0-12.5), and 0 (0 18.8), respectively. CONCLUSIONS: Competitive soccer players undergoing arthroscopic capsulolabral repair with knotless suture anchors for shoulder instability without significant bone loss demonstrate excellent return to play at mid-to-long-term follow-up, with a 10.5 % chances of re-dislocating. LEVEL OF EVIDENCE: IV. PMID- 26685690 TI - Changes in coronal alignment of the ankle joint after high tibial osteotomy. AB - PURPOSE: The purpose of this study was to investigate changes in coronal alignment of the ankle joint after HTO. Our hypothesis was that ankle joint orientation may become more parallel or less parallel to the ground after HTO, and this change may affect ankle symptoms. METHODS: Eighty-six knees were retrospectively analysed after HTO for varus osteoarthritis. Preoperative and follow-up whole-leg radiographs were taken. The hip-knee-ankle (HKA) angle and medial proximal tibial angle (MPTA) were measured to evaluate coronal alignment of the knee. Tibial plafond inclination (TPI), talar inclination (TI), talar tilt (TT), and lateral distal tibial angle (LDTA) were measured to evaluate coronal alignment of the ankle. Patients were divided into two groups: those who exhibited a decrease in the absolute value of TPI and TI after HTO (group A) and those who exhibited an increase in the absolute value of TPI or TI after HTO (group B). Clinical outcomes of the knee and ankle were evaluated pre- and postoperatively. RESULTS: Mean TPI and TI changed from 6.9 degrees +/- 3.6 degrees and 8.0 degrees +/- 3.8 degrees to 2.8 degrees +/- 3.1 degrees and 3.9 degrees +/- 3.0 degrees in group A (P < 0.001 for both) and from -1.3 degrees +/- 3.7 degrees and 0.6 degrees +/- 4.5 degrees to -6.0 degrees +/- 4.2 degrees and -4.6 degrees +/- 5.9 degrees in group B (P = 0.018 for both). VAS for ankle pain did not change significantly after HTO (n.s.) in group A, whereas those of group B increased significantly after HTO (P = 0.014). CONCLUSION: Ankle joint orientation becomes more parallel or less parallel to the ground after HTO. Smaller preoperative HKA and LDTA result in a more valgus ankle joint orientation after HTO. Ankle symptoms were affected by coronal alignment changes of the ankle after HTO. LEVEL OF EVIDENCE: III. PMID- 26685691 TI - Efficacy of intra-articular hyaluronic acid injections and exercise-based rehabilitation programme, administered as isolated or integrated therapeutic regimens for the treatment of knee osteoarthritis. AB - PURPOSE: To assess the efficacy of intra-articular hyaluronic acid (HA) injections and exercise-based rehabilitation (EBR) programme, administered as isolated or integrated for the treatment of knee osteoarthritis. METHODS: One hundred sixty-five patients affected by moderate degrees of knee OA were randomly divided into three groups. Group 1 (HA) underwent three HA injections (one every 2 weeks); group 2 (EBR) underwent 20 treatment sessions in a month of an individualized programme; and group 3 (HA + EBR) received both treatments simultaneously. Primary outcome was the Italian version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; secondary outcome was the evaluation of active range of movement (AROM). All patients were evaluated before and 1, 3 and 6 months after treatment. Significance was set at p < 0.05. RESULTS: Two patients in each group were lost to follow-up. No adverse events occurred. All groups experienced improvements at 1-month follow-up. No further improvements could be detected within groups over time. At 1-month follow-up, WOMAC pain subscale showed significant improvement in group 3 compared to group 1 (p = 0.043). WOMAC pain, stiffness and function subscales showed that group 2 significantly worsened between 1 and 6 months after treatment (p = 0.004, p = 0.026 and p = 0.025, respectively). AROM revealed no significant differences between and within groups over time. CONCLUSIONS: Intra-articular HA injections and individualized rehabilitation programmes administered in isolation or in combination are effective in improving knee function and pain relief. The combined treatment showed the greatest pain relief at 1-month follow-up compared to either in isolation. Compared to the previous studies, this is the first study, which proposed an EBR programme tailored to the compartment of the knee joint most involved in the degenerative process. LEVEL OF EVIDENCE: I. PMID- 26685692 TI - Effects of gastrocnemius recession on ankle motion, strength, and functional outcomes: a systematic review and national healthcare database analysis. AB - PURPOSE: The purpose of this systematic review was to report the effects of gastrocnemius recession on ankle dorsiflexion range of motion, function, and push off power. METHODS: The MEDLINE and EMBASE databases were reviewed with terms "gastrocnemius recession". The inclusion criteria were: (1) clinical studies, (2) published in a peer-reviewed journal within the past 10 years, and (3) published in English. Excluded were: (1) review articles, (2) cadaveric studies, (3) studies including patients under the age of 18 years, (4) studies evaluating a neurologic condition, (5) level of evidence 5, and (6) Quality of Evidence Score <3. Data were then extracted and analysed for trends. The PearlDiver Database was also used to review de-identified patient information retrospectively between 2007 and 2011. RESULTS: Full-text review yielded 23 articles that fit the inclusion criteria. Twenty-one of 23 (91%) and 2/23 (9%) studies were level of evidence 4 and 3, respectively. Twelve of 23 (52%) studies reported follow-up assessment between 12 and 36 months, and no studies reported longer-term follow up. Twelve of 12 (100%) studies reported improved dorsiflexion range of motion 9/9 (100%) reported improved AOFAS, and 11/11 (100%) reported improved VAS. Five of 23 (22%) studies reported strength in a measured and controlled fashion with variable results, but of these, no study reported a return to normal power. The mean complication rate was 14%. CONCLUSION: The available evidence supports that GR improves functional outcomes and increases dorsiflexion range of motion. Furthermore, GR affects gait kinematics, which may cause compensatory effects at the knee, ankle, and subtalar joints. Evidence has shown that power does not return to normal levels. Clinicians may utilize these data clinically to determine whether patients may benefit from GR or not. LEVEL OF EVIDENCE: IV. PMID- 26685694 TI - ACL tear in kids: serious injury with high risk of osteoarthritis. PMID- 26685693 TI - History of shoulder instability surgery. AB - PURPOSE: The surgical management of shoulder instability is an expanding and increasingly complex area of study within orthopaedics. This article describes the history and evolution of shoulder instability surgery, examining the development of its key principles, the currently accepted concepts and available surgical interventions. METHODS: A comprehensive review of the available literature was performed using PubMed. The reference lists of reviewed articles were also scrutinised to ensure relevant information was included. RESULTS: The various types of shoulder instability including anterior, posterior and multidirectional instability are discussed, focussing on the history of surgical management of these topics, the current concepts and the results of available surgical interventions. CONCLUSIONS: The last century has seen important advancements in the understanding and treatment of shoulder instability. The transition from open to arthroscopic surgery has allowed the discovery of previously unrecognised pathologic entities and facilitated techniques to treat these. Nevertheless, open surgery still produces comparable results in the treatment of many instability-related conditions and is often required in complex or revision cases, particularly in the presence of bone loss. More high-quality research is required to better understand and characterise this spectrum of conditions so that successful evidence-based management algorithms can be developed. LEVEL OF EVIDENCE: IV. PMID- 26685695 TI - The split portal: Description of a new accessory posterior portal for arthroscopic shoulder instability procedures. AB - PURPOSE: Open approach to the posterior shoulder during bone block for posterior shoulder instability is challenging. Anatomical study was performed to identify landmarks of a portal, avoiding soft tissue damage, between the infraspinatus (IS) and teres minor (TM) muscles and distant from the supra-scapular nerve (SSN) for arthroscopic shoulder bone block. METHODS: Eight fresh-frozen cadaveric shoulder specimens were used. The arthroscope was introduced through the soft point (SP). A guide wire was placed through the SP, in the rotator interval direction. A posterior open dissection exposed the split between the IS and TM. A new guide wire was placed into the split, parallel to the first wire, to locate the new posterior arthroscopic approach. Ten distances were measured to define the safe position. RESULTS: The mean values were: SP to split IS-TM: 2 +/- 0.2 (2 2.8); spinal bone to split IS-TM: 5 +/- 0.5 (3-6.2); split IS-TM to posterior glenoid 6 o'clock: 1.3 +/- 0.3 (0.6-1.6), 9 o'clock: 1.5 +/- 0.3 (1-1.9), and 12 o'clock: 2 +/- 0.1 (2.1-2.4); SSN to posterior glenoid 6 o'clock: 2.4 +/- 0.2 (2.1-2.6), 9 o'clock: 1.7 +/- 0.1 (1.5-1.8), and 12 o'clock: 1.5 +/- 0.3 (1.2 2.1); and SSN to split IS-TM: 2 +/- 0.3 (1.2-2.1). CONCLUSION: This preliminary anatomical study described a posterior arthroscopic portal located 2 cm under the SP, parallel to the SP portal direction, and finishing between 7 and 8 o'clock at the posterior rim of the glenoid. For arthroscopic shoulder bone block, this portal can avoid muscle and SSN lesions. PMID- 26685696 TI - Fixation of stem in revision of total knee arthroplasty: cemented versus cementless-a meta-analysis. AB - PURPOSE: Revision of total knee arthroplasty (TKA) is growing rapidly all over the world. The introduction of intramedullary stems for additional stability in revision is well accepted by most of the surgeons, while the philosophy of stem fixation is still under controversy. A meta-analysis was performed to compare the survivorship of revised implants with regard to a cemented or cementless stem fixation. METHODS: Publications with patients who underwent revision TKA with minimum 24-month follow-up were systematically reviewed. Type of intramedullary stem fixation, failure rate for any reason, incidence of aseptic loosening and infection were extracted with follow-up interval specified. Random-effects meta analysis was used to aggregate incidence data, which was compared between different fixation groups by fitting of logistic regression model. RESULTS: Seventeen observational studies were included in this meta-analysis. There was a similar likelihood of failure for any reason (risk ratio, RR 0.97), general reoperation (RR 1.02), aseptic loosening (RR 1.0) and infection (RR 1.0) in cemented stem fixation group compared to cementless stem fixation group with follow-up <60 months. When follow-up period extend to more than 60 months, the same likelihood was observed as 0.98, 0.96, 0.97 and 0.98, respectively. There was no significant difference in any of these comparisons of survival-related indices. CONCLUSION: There was no significant difference in failure for any reason, reoperation, aseptic loosening and infection between revision TKA with cemented or cementless stem fixation. Based on the available literature, no superiority of any type of stem fixation was found. If follow-up period was neglected, aseptic loosening would be the leading reason for pain and dysfunction of patient undertaken revision TKA. LEVEL OF EVIDENCE: Systematic review of Level IV, Therapeutic studies, Level IV. PMID- 26685697 TI - Sexual health problems in French cancer survivors 2 years after diagnosis-the national VICAN survey. AB - PURPOSE: The purpose of this study is to assess French cancer survivors' sexual health 2 years after diagnosis. METHODS: Using the French National Health Insurance System database, the representative national VICAN survey was created comprising 4349 adults (12 cancer sites), still alive 2 years after diagnosis and aged 18-52 ("younger") or 53-82 ("older"). Sexual health was evaluated using six items from the Relationship and Sexuality Scale, and an overall indicator was created. RESULTS: Among the study's 1955 sexually active participants, 18.6 % (versus 13.1 %), 39.8 % (versus 39.9 %) and 29.4 % (versus 29.8 %) of men (versus women) were affected, respectively, by "strong", "moderate" and "weak" sexual health deterioration, while 12.2 % (versus 17.1 %) were spared sexual problems (P = 0.001). Strong deterioration more often concerned older men with prostate (27.7 %) and lung (26.1 %) cancers, younger men with upper aero-digestive tract cancers (25.2 %) and women (younger/older) with cervical cancer (24.2 %). Substantial (strong/moderate) sexual health deterioration was observed for all cancer sites, rates ranging from 68.3 % (prostate) to 37.2 % (melanoma). In all four gender/age subgroups, increasing age predicted poorer sexual health, although statistical significance was not reached in older women. Apart from genital cancer, perceived consequences, such as general sequelae and fatigue, were the primary factors associated with severe sexual problems. CONCLUSIONS: Two years after diagnosis, the majority of sexually active French cancer survivors reported impaired sexual health. Younger and older men and women with cancer in non-reproductive sites also reported problems. IMPLICATIONS FOR CANCER SURVIVORS: Interventions aimed at improving sexual health irrespective of age and cancer site should be developed. PMID- 26685698 TI - Cloning, Expression and Characterization of Recombinant, NADH Oxidase from Giardia lamblia. AB - The NADH oxidase family of enzymes catalyzes the oxidation of NADH by reducing molecular O2 to H2O2, H2O or both. In the protozoan parasite Giardia lamblia, the NADH oxidase enzyme (GlNOX) produces H2O as end product without production of H2O2. GlNOX has been implicated in the parasite metabolism, the intracellular redox regulation and the resistance to drugs currently used against giardiasis; therefore, it is an interesting protein from diverse perspectives. In this work, the GlNOX gene was amplified from genomic G. lamblia DNA and expressed in Escherichia coli as a His-Tagged protein; then, the enzyme was purified by immobilized metal affinity chromatography, characterized, and its properties compared with those of the endogenous enzyme previously isolated from trophozoites (Brown et al. in Eur J Biochem 241(1):155-161, 1996). In comparison with the trophozoite-extracted enzyme, which was scarce and unstable, the recombinant heterologous expression system and one-step purification method produce a stable protein preparation with high yield and purity. The recombinant enzyme mostly resembles the endogenous protein; where differences were found, these were attributable to methodological discrepancies or artifacts. This homogenous, pure and functional protein preparation can be used for detailed structural or functional studies of GlNOX, which will provide a deeper understanding of the biology and pathogeny of G. lamblia. PMID- 26685699 TI - Nucleic acid-amplification testing for hepatitis B in cornea donors. AB - Careful donor selection and implementation of tests of appropriate sensitivity and specificity are of paramount importance for minimizing the risk of transmitting infectious diseases from donors to corneal allograft recipients. Reported cases of viral transmission with corneal grafts are very unusual. Nevertheless potential virus transmission through the engraftment cannot be ruled out. According to European Guideline 2006/17/EC, screening for antibodies for Hepatitis B core antigen (anti HBc) is mandatory, and when this test is positive, some criteria must be established before using corneas. Despite the continuous progress in screening tests, donors carrying an occult hepatitis B infection (OBI) can cause transplant-transmitted hepatitis B. To date, Nucleic Acid Testing (NAT) is not an obligatory assay in corneal tissue setting neither in our country nor in the rest of European countries. Herein, we report three cornea donors that were rejected with the diagnosis of OBI through the testing of sensitive NAT and the serological profile of Hepatitis B virus. The aim of this report is to emphasize the need to include NAT in new reviews of EU Tissues and Cells Directives in order to increase level of security in tissue donation as well as not to reject a high number of donors with isolated profile of anti HBc in geographical areas with high prevalence of Hepatitis B, that could be rejected without a true criterion of Hepatitis B infection. PMID- 26685700 TI - Supplemental description and molecular characterization of Myxobolus miyarii Kudo, 1919 (Myxosporea: Myxobolidae) infecting intestine of Amur catfish (Silurus asotus). AB - Myxobolus miyairii Kudo, 1919 was first reported from the intestines of the Amur catfish (Silurus asotus) in Japan and then in China and Russia, but with incomplete description. During the investigation of fish myxosporean diversity in Poyang Lake, the biggest lake along the Yangtze River, China, two Amur catfish highly infected with M. miyairii in the intestine wall were sampled. So, the complete description of this species with morphological and molecular data was presented here. A large number of whitish, round or ellipsoidal pseudocysts 0.32 0.78 mm in diameter could be found in the external intestinal wall after dissecting the infected fish. Mature spores of M. miyairii were elongated and ellipsoidal in the frontal view and narrow fusiform in the lateral view, with a slightly pointed anterior end and a bluntly rounded posterior end and measured 13.3 +/- 0.49 (12.5-14.7) MUm * 6.6 +/- 0.27 (6.2-7.4) MUm * 5.0 +/- 0.26 (4.4 5.7) MUm in size. Spore surface was smooth and two spore valves symmetrical, with a thin and straight sutural ridge. Interestingly, two types of caudal appendage (single or bifurcated) were occasionally present on the posterior end of some spores which has not previously been reported. The two equal pyriform polar capsules measured 6.5 +/- 0.30 (6.2-7.5) MUm long and 1.9 +/- 0.14 (1.5-2.3) MUm wide and situated at the anterior end of the spore. Polar filaments coiled with eight to nine turns, perpendicularly to the longitudinal axis of the polar capsules. Histopathological analysis showed that the plasmodium developed in the circular muscle layer of intestinal wall of Amur catfish, but no obvious inflammatory responses were observed. Phylogenetic analysis based on the partial 18S small subunit ribosomal DNA sequences indicates that M. miyairii cluster within a clade of Siluriforme-infecting Henneguya species with the support of a high bootstrap value, but also evolutionarily independent from the Henneguya clade infecting the epithelium of fish of the Ictaluridae family. Additionally, Myxobolus species reported with caudal processes dispersed within the Henneguya Myxobolus clade. PMID- 26685701 TI - Vilazodone for cannabis dependence: A randomized, controlled pilot trial. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the efficacy of vilazodone, a selective serotonin receptor inhibitor and partial 5-HT1A agonist, for treatment of cannabis dependence. METHODS: Seventy-six cannabis dependent adults were randomized to receive either up to 40 mg/day of vilazodone (n = 41) or placebo (n = 35) for 8 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests; secondary outcomes included cannabis use self-report and cannabis craving. RESULTS: Participants in both groups reported reduced self-reported cannabis use over the course of the study; however, vilazodone provided no advantage over placebo in reducing cannabis use. Men had significantly lower creatinine-adjusted cannabinoid levels and a trend for increased negative urine cannabinoid tests than women. DISCUSSION AND CONCLUSIONS: Vilazodone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes than men. SCIENTIFIC SIGNIFICANCE: Further medication development efforts for cannabis use disorders are needed, and gender should be considered as an important variable in future trials. PMID- 26685702 TI - Membrane positioning for high- and low-resolution protein structures through a binary classification approach. AB - The critical importance of algorithms for orienting proteins in the lipid bilayer stems from the extreme difficulty in obtaining experimental data about the membrane boundaries. Here, we present a computational method for positioning protein structures in the membrane, based on the sole alpha carbon coordinates and, therefore, compatible with both high and low structural resolutions. Our algorithm follows a new and simple approach, by treating the membrane assignment problem as a binary classification. Compared with the state-of-the-art algorithms, our method achieves similar accuracy, while being faster. Finally, our open-source software is also capable of processing coarse-grained models of protein structures. PMID- 26685703 TI - A new approach for standardization and increased accuracy of lymph node washout thyroglobulin in patients with differentiated thyroid carcinoma. AB - BACKGROUND: High values of fine needle aspiration washout thyroglobulin (FNAB-Tg) are diagnostic for metastatic lesions of thyroid cancer. However, there is not a consensus on cutoff for high FNAB-Tg level. In this study, we aimed to determine a more accurate and standardized parameter for FNAB-Tg. METHODS: Ultrasonographically suspicious lymph nodes of patients with histopathologically confirmed differentiated thyroid cancer or malignant/suspicion for malignancy cytology were included. Tg washout was obtained by aspiration and nonaspiration fine needle biopsy (nonaspiration-FNB). Simultaneous Tg was measured from serum. Aspiration and washout procedures were also performed from whole blood and serum using syringes and needles identical to ones used for lymph node biopsy. RESULTS: Data of 19 lesions in 17 patients who underwent lymph node dissection were analyzed. Nonaspiration FNB-Tg, FNAB-Tg/whole blood washout-Tg, nonaspiration FNB Tg/whole blood washout-Tg, nonaspiration FNB-Tg/serum washout-Tg, nonaspiration FNB-Tg/serum Tg ratios were significantly higher in malignant lymph nodes compared to benign ones. Areas under the ROC curve for nonaspiration FNB-Tg, FNAB Tg/whole blood washout-Tg, FNAB-Tg/serum washout-Tg, nonaspiration FNB-Tg/whole blood washout-Tg, nonaspiration FNB-Tg/serum washout-Tg, and nonaspiration FNB Tg/serum Tg were statistically significant for the discrimination of benign and malignant lymph nodes. Best cutoff value for nonaspiration FNB-Tg was 4.21. Among ratios, best cutoff values were 5.40 for nonaspiration FNB-Tg/whole blood washout Tg and 3.28 for nonaspiration FNB-Tg/serum washout-Tg. CONCLUSION: For detection of malignant lymph nodes, determining ratios of nonaspiration FNB-Tg to whole blood and/or serum washout-Tg might be a promising method to increase accuracy and provide standardization of lymph node washout procedure. PMID- 26685705 TI - Climate change must be considered in short- and long-term monitoring and assessment. PMID- 26685706 TI - Obese people's perceptions of the thin ideal. AB - The media play a key role in promoting the thin ideal. A qualitative study, in which we used in depth interviews and thematic analysis, was undertaken to explore the attitudes of 142 obese individuals toward media portrayals of the thin ideal. Participants discussed the thin ideal as a social norm that is also supported through the exclusion of positive media portrayals of obese people. They perceived the thin ideal as an 'unhealthy' mode of social control, reflecting on their personal experiences and their concerns for others. Participants' perceptions highlighted the intersections between the thin ideal and gender, grooming and consumerism. Participants' personal responses to the thin ideal were nuanced--some were in support of the thin ideal and some were able to critically reflect and reject the thin ideal. We consider how the thin ideal may act as a form of synoptical social control, working in tandem with wider public health panoptical surveillance of body weight. PMID- 26685704 TI - Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study. AB - The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA. PMID- 26685707 TI - A discrete-time analysis of the effects of more prolonged exposure to neighborhood poverty on the risk of smoking initiation by age 25. AB - Evidence suggests that individuals who initiate smoking at younger ages are at increased risk for future tobacco dependence and continued use as well as for numerous smoking-attributable health problems. Identifying individual, household, and to a far lesser extent, contextual factors that predict early cigarette use has garnered considerable attention over the last several decades. However, the majority of scholarship in this area has been cross-sectional or conducted over relatively short windows of observation. Few studies have investigated the effects of more prolonged exposure to smoking-related risk factors, particularly neighborhood characteristics, from childhood through early adulthood. Using the 1970-2011 waves of the Panel Study of Income Dynamics merged with census data on respondents' neighborhoods, this study estimates a series of race-specific discrete-time marginal structural logit models for the risk of smoking initiation as a function of neighborhood poverty, as well as individual and household characteristics, from ages four through 25. Neighborhood selection bias is addressed using inverse-probability-of-treatment weights. Results indicate that more prolonged exposure to high (>20%) as opposed to low (<10%) poverty neighborhoods is associated with an increased risk of smoking onset by age 25, although consistent with prior literature, this effect is only evident among white and not nonwhite youth and young adults. PMID- 26685709 TI - Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression. AB - Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect. PMID- 26685708 TI - Birth weight, early life course BMI, and body size change: Chains of risk to adult inflammation? AB - This paper examines how body size changes over the early life course to predict high sensitivity C-reactive protein in a U.S. based sample. Using three waves of the National Longitudinal Study of Adolescent Health (Add Health), we test the chronic disease epidemiological models of fetal origins, sensitive periods, and chains of risk from birth into adulthood. Few studies link birth weight and changes in obesity status over adolescence and early adulthood to adult obesity and inflammation. Consistent with fetal origins and sensitive periods hypotheses, body size and obesity status at each developmental period, along with increasing body size between periods, are highly correlated with adult CRP. However, the predictive power of earlier life course periods is mediated by body size and body size change at later periods in a pattern consistent with the chains of risk model. Adult increases in obesity had effect sizes of nearly 0.3 sd, and effect sizes from overweight to the largest obesity categories were between 0.3 and 1 sd. There was also evidence that risk can be offset by weight loss, which suggests that interventions can reduce inflammation and cardiovascular risk, that females are more sensitive to body size changes, and that body size trajectories over the early life course account for African American- and Hispanic-white disparities in adult inflammation. PMID- 26685710 TI - A Facile Method to Prepare Double-Layer Isoporous Hollow Fiber Membrane by In Situ Hydrogen Bond Formation in the Spinning Line. AB - A double-layer hollow fiber is fabricated where an isoporous surface of polystyrene-block-poly(4-vinylpyridine) is fixed on a support layer by co extrusion. Due to the sulfonation of the support layer material, delamination of the two layers is suppressed without increasing the number of subsequent processing steps for isoporous composite membrane formation. Electron microscope energy-dispersive X-ray spectroscopy images unveil the existence of a high sulfur concentration in the interfacial region by which in-process H-bond formation between the layers is evidenced. For the very first time, our study reports a facile method to fabricate a sturdy isoporous double-layer hollow fiber. PMID- 26685711 TI - Changes in Spectra and Conformation of Hairpin DNA-Stabilized Silver Nanoclusters Induced by Stem Sequence Perturbations. AB - It is well-known that even small perturbations of the DNA sequence can drastically and unpredictably disrupt or alter the fluorescence of DNA-stabilized silver nanoclusters (DNA-AgNCs). Understanding how the structure of DNA affects the nanocluster that it stabilizes is the key to rationalizing such effects. We approach this challenge by strategically modifying the stem sequence of a hairpin DNA that hosts a spectrally pure, red-emitting nanocluster. Most of our modifications (base composition, sequence orientation, and loop location) reduce AgNC fluorescence in purity and shift it in wavelength, but one modification (appending poly(thymidine) to the 3' end of the stem) is inert with respect to fluorescence. Microfluidic capillary electrophoresis reveals that all of the modifications induce conformational changes of the DNA and that the original, spectrally pure nanocluster exists in two structurally distinct conformations. Interestingly, appending five or more thymidines, despite having no effect on fluorescence, eliminates this structural degeneracy. To explain this result, we propose that the original spectrally pure cluster is stabilized by a pair of hairpins whose stems can arrange in either a cis or trans orientation. Finally, we quantify the extent to which thymidine appendages of different lengths can be used to fine-tune the electrophoretic mobility of DNA-AgNC. PMID- 26685712 TI - Technological process for cell disruption, extraction and encapsulation of astaxanthin from Haematococcus pluvialis. AB - In this work, the effectiveness of different enzymatic techniques for cell wall disruption of Haematococcus pluvialis for the extraction of carotenoids and subsequent encapsulation of extracts in the co-polymer poly(hydroxybutyrate-co hydroxyvalerate) (PHBV) using the Solution Enhanced Dispersion by Supercritical fluids (SEDS) technique was investigated. Glucanex((r)) performed best compared with Lyticase((r)) and Driselase((r)). The conditions for enzymatic lysis using this enzyme preparation were established as a pH of 4.5, a temperature of 55 degrees C, an initial activity of beta-1,3-glucanase of 0.6 U mL(-1) and a reaction time of 30 min. Enzymatic lysis assisted by ultrasound without biomass freezing was shown to be a promising and simple one-step technique for cell wall disruption, reaching 83.90% extractability. In the co-precipitation experiments, the highest encapsulation efficiency (51.21%) was obtained when using a higher biomass to dichloromethane ratio (10 mg mL(-1)) at the carotenoid extraction step and a lower pressure of precipitation (80 bar). In these conditions, spherical particles in the micrometer range (0.228 MUm) were obtained. PMID- 26685713 TI - Association between serum fetuin-A level and erectile function. AB - Recent studies have shown that ED is an early symptom of atherosclerosis. Fetuin A, a glycoprotein secreted by the liver, kidneys and choroid plexus, has been linked to systemic fibrosis and calcification in human and rat studies. Deficiency of this compound may play a role in atherosclerosis and cardiovascular disease progression. The aim of the study was to examine whether serum fetuin-A level is related to erectile function or severity of ED. Sixty ED patients without cardiovascular disease were assigned to one of the three groups (mild, moderate or severe ED) depending on ED severity. Twenty healthy volunteers were included as the control group. The International Index of Erectile Function-5 questionnaire was used to measure erection quality in all four groups. Mean age, body mass index, total testosterone, low- and high-density lipoprotein cholesterol, and triglyceride levels did not significantly differ between the three erectile dysfunction and control groups (P > 0.05). The group with severe ED had a significantly lower mean fetuin-A level than the mild ED and control groups. For both mild and moderate ED groups, the mean serum fetuin-A level was significantly lower in comparison with the control group (P < 0.001). Serum fetuin-A level may be used as a supplemental biochemical parameter in preliminary evaluation of ED. PMID- 26685714 TI - Construction of a polyhedron decorated MOF with a unique network through the combination of two classic secondary building units. AB - A novel decorated metal-organic polyhedron (MOP) based metal-organic framework with a unique 4,9-connected network is successfully constructed, which displays a relatively strong interaction toward H2 and CO2 probably due to the existence of open metal sites in the secondary building units. PMID- 26685715 TI - Neuropsychiatric symptoms among adult patients with aseptic meningitis: a prospective case series. PMID- 26685716 TI - Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children. AB - Magnesium ions are essential to the basic metabolic processes in the human body. Previous genetic studies indicate that serum magnesium levels are highly heritable, and a few genetic loci have been reported involving regulation of serum magnesium in adults. In this study, we examined if additional loci influence serum magnesium levels in children. We performed a genome-wide association study (GWAS) on 2,267 European-American children genotyped on the Illumina HumanHap550 or Quad610 arrays, sharing over 500,000 markers, as the discovery cohort and 257 European-American children genotyped on the Illumina Human OmniExpress arrays as the replication cohort. After genotype imputation, the strongest associations uncovered were with imputed SNPs residing within the FGFR2 (rs1219515, P = 1.1 * 10(-5)) and PAPSS2 (rs1969821, P = 7.2 * 10(-6)) loci in the discovery cohort, both of which were robustly replicated in our independent patient cohort (rs1219515, P = 3.5 * 10(-3); rs1969821, P = 1.2 * 10( 2)). The associations at the FGFR2 locus were also weakly replicated in a dataset from a previous GWAS of serum magnesium in European adults. Our results indicate that FGFR2 and PAPSS2 may play an important role in the regulation of magnesium homeostasis in children of European-American ancestry. PMID- 26685717 TI - Developmental competence of oocytes grown in vitro: Has it peaked already? AB - In vitro growth of immature oocytes provides opportunities to increase gametic resources and to understand the mechanisms underlying oocyte development. Many studies on the in vitro growth of oocytes have been reported thus far; however, only a few cases have been reported, which demonstrated that oocytes can support full-term development after in vitro fertilization. Our research group recently found that culture of mouse neonatal primordial follicles increased the birthrate; however, the establishment of an in vitro system that can completely mimic follicle or oocyte growth in vivo and control oogenesis remains an ongoing challenge. PMID- 26685718 TI - Propranolol versus captopril in the treatment of infantile hemangioma (IH): A randomized controlled trial. AB - BACKGROUND: Renin-angiotensin system components have been demonstrated in the biology of infantile hemangioma (IH). Captopril, an angiotensin-converting enzyme inhibitor, is proposed as a therapeutic alternative to oral propranolol. OBJECTIVES: We sought to compare the benefit of propranolol and captopril in the treatment of IH, and to assess angiotensin-converting enzyme gene polymorphism in patients with IH and in control subjects. METHODS: Thirty patients with IH and 35 healthy control subjects were enrolled in this study. Patients were randomly assigned to treatment with either propranolol or captopril. Assessment was done clinically and by measurement of serum vascular endothelial growth factor and angiotensin II in patients and control subjects. Angiotensin-converting enzyme gene polymorphism was also studied. RESULTS: Clinical improvement was significantly better and faster in the patients treated with propranolol. Both groups showed reduced vascular endothelial growth factor and angiotensin II levels posttreatment, with a significantly higher percentage reduction in the propranolol-treated group. Cardiac side effects were reported only in the captopril-treated group. Baseline vascular endothelial growth factor level was significantly higher, and baseline angiotensin II level was significantly lower, in patients than control subjects. LIMITATIONS: We studied a relatively small number of patients and control subjects. CONCLUSION: Propranolol shows greater benefit than captopril in the treatment of IH. PMID- 26685719 TI - A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards. AB - BACKGROUND: Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear. OBJECTIVES: We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD. METHODS: We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features. RESULTS: Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7 point scales. North American studies used global assessments more commonly than studies from other countries. LIMITATIONS: The search was restricted to the Global Resource of Eczema Trials database. CONCLUSION: Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required. PMID- 26685720 TI - Epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia (ALHE): A systematic review. AB - BACKGROUND: Current knowledge of angiolymphoid hyperplasia with eosinophilia (ALHE) derives from retrospective reports and case series, leading to a nonevidence-based treatment approach. OBJECTIVE: We sought to systematically review the literature relating to cutaneous ALHE to estimate its epidemiology and treatment outcomes. METHODS: A literature search of PubMed, EMBASE, Web of Science, and Google Scholar was conducted. Articles detailing cases of histologically confirmed cutaneous ALHE were included. RESULTS: In all, 416 studies were included in the review, representing 908 patients. There was no sex predominance among patients with ALHE. Mean age at presentation was 37.6 years. There was a significant association between presence of multiple lesions and pruritus, along with bleeding. Surgical excision was the most commonly reported treatment for ALHE. Treatment failure was lowest for excision and pulsed dye laser. Mean disease-free survival after excision was 4.2 years. There were higher rates of recurrence postexcision with earlier age of onset, longer duration of disease, multiple lesions, bilateral lesions, pruritus, pain, and bleeding. LIMITATIONS: Potential for publication bias is a limitation. CONCLUSIONS: Surgical excision appears to be the most effective treatment for ALHE, albeit suboptimal. Pulsed dye and other lasers may be effective treatment options. More studies are needed to improve the treatment of ALHE. PMID- 26685721 TI - Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). PMID- 26685722 TI - Fine particles sampled at an urban background site and an industrialized coastal site in Northern France - Part 1: Seasonal variations and chemical characterization. AB - The chemical composition of particulate matter sampled at two French Northern sites (Douai, DO - urban background; Grande-Synthe, GS - industrialized coastal site) was investigated during two summer and winter field campaigns at each site. Measurements of the major chemical species (organic, sulfate, nitrate, ammonium, chloride) in the non-refractory submicron aerosols (NR-PM1) were carried out by a High Resolution Time-of-Flight Aerosol Mass Spectrometer. Black Carbon in PM2.5 was monitored using an Aethalometer, while the OC and EC fractions and some targeted chemical organic families (polycyclic aromatic hydrocarbons, PAHs; dicarboxylic acids, DCAs) were quantified by the simultaneous collection of PM2.5 on filters followed by offline analyses. The seasonal trends and winter-to-summer (W/S) concentration ratios are discussed in this paper. Results indicate that the total average mass concentrations of PM2.5 varied between 20.5MUgm-3 and 32.6MUgm 3 in DO and between 10.6MUgm-3 and 29.9MUgm-3 in GS during summer and winter, respectively. Similar concentration patterns were found for PAHs and Organic Carbon (OC, representing ~80% of the total carbon) with highest concentrations in winter at the urban site. DCA concentrations showed less seasonal variations, although the highest value also appeared during winter. Total NR-PM1 presented concentrations in summer lower by a factor of 4 (for DO) and 10 (for GS) than those observed in winter. Organics and nitrates dominated the NR-PM1 in DO for both seasons and during winter in GS while sulfates and nitrates were the most dominant species in summer in GS. Average chloride concentrations were slightly more important in GS than those in DO related to its use in industrial processes and no significant seasonal trend was observed. The size-resolved chemical composition showed that aerosols sampled in DO in winter are more aged than those collected in GS where fresh emissions of sulfate from the industrial sector were observed. PMID- 26685723 TI - Nanoscale adsorbed structures as a robust approach for tailoring polymer film stability. AB - The stability or wettability of thin polymer films on solids is of vital interest in traditional technologies as well as in new emerging nanotechnologies. We report here that nanoscale structures of polymer chains adsorbed onto a solid surface play a crucial role in the thermal stability of the film. In this study, polystyrene (PS) spin-cast films (20 nm in thickness) with eight different molecular weights prepared on silicon (Si) substrates were used as a model. When low molecular weight (Mw<= 50 kDa) PS films were subjected to thermal annealing at temperatures far above the bulk glass transition temperature, dewetting occurred promptly, while high molecular weight (Mw>= 123 kDa) PS films were stable for at least 6 weeks at 150 degrees C. We reveal a strong correlation between the film stability and the two different interfacial structures of the adsorbed polymer chains: their opposing wettability against chemically identical free polymer chains results in a wetting-dewetting transition at the adsorbed polymer-free polymer interface. This is a unique aspect of the stability of polymer thin films and may be generalizable to other polymer systems regardless of the magnitude of solid-polymer attractive interactions. PMID- 26685724 TI - Effect of particle size on the biodistribution of nano- and microparticles following intra-articular injection in mice. AB - Intra-articular (IA) injection of extended drug release forms based on biodegradable microparticles holds promise for the treatment of joint diseases. However, the fate of microparticles following intra-articular injection is controversial and has not been thoroughly investigated. The aim of this work was therefore to evaluate the biodistribution of fluorescent poly(lactic acid) particles of different sizes after IA injection in arthritic or healthy mice. Regardless of the inflammatory status of the joint, 300 nm-nanoparticles leaked from the joint. Due to inflammation and related increase of vascular permeability, 3 MUm-microparticles that were retained in the non-inflamed synovial membrane leaked from the inflamed joint. Complete retention of 10 MUm microparticles was observed independently of the joint inflammatory status. Embedding particles in a hyaluronic acid gel prolonged the retention of the formulations only in inflamed joints. Depending on particle's size, formulations were preferentially eliminated by blood vessels or lymphatic pathways. Poly(lactic acid) particles of 3 MUm were biocompatible and retained in knee joints at least for 6 weeks. This work highlights the need to deliver hyaluronic acid-embedded particles of at least 3 MUm to guarantee their retention in inflamed joints. These results will contribute to the rational design of long lasting formulations to treat acute and chronic joint diseases. PMID- 26685725 TI - Synergistic effect of PEGylated resveratrol on delivery of anticancer drugs. AB - Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. PMID- 26685726 TI - Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration. AB - The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25 degrees C and 37 degrees C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant. PMID- 26685727 TI - Evaluation of the versatile character of a nanoemulsion formulation. AB - The formulate-ability of six model active pharmaceutical ingredients (API), with different physico-chemical profiles, in a nanoemulsion designed to be intraveinously administrable was explored. Nanoemulsions were spontaneously generated at room temperature by pouring a phosphate buffer in an anhydrous mixture containing pharmaceutically acceptable triglycerides and non-ionic surfactants. After determination of the apparent solubility of each API in excipients and characterization of mixtures by DSC, API-loaded nanoemulsions were formulated and characterized in terms of granulometric properties, surface potential, drug recovery efficiency, pH, osmolarity, in vitro drug release, and stability. Except ciprofloxacin, a BCS class IV drug, all studied APIs were soluble in at least one excipient used, i.e. Labrasol. At 2 wt% API, all drug loaded nanoemulsions present properties compatible with i.v. administration. The formulation should permit to increase apparent solubility of poorly water-soluble APIs, and also to prolong delivery of hydrophobic as well of more hydrophilic compounds. Herein, the relative affinity of the API for nanodroplets and the release medium would directly influence drug release profiles. Nanoemulsions were stable for 7 days. They could also been extemporaneously reconstituted before use. Such a versatile nanoemulsion would provide a valuable option as formulation strategy for improvement of drug properties. PMID- 26685728 TI - Tween 20 increases intestinal transport of doxorubicin in vitro but not in vivo. AB - The chemotherapeutic drug substance doxorubicin has been reported to be a substrate of P-gp, which induces a barrier for oral administration and leads to a bioavailability of 3% in male Sprague Dawley rats. Literature studies have reported increased transport of P-pg substrates, like digoxin, when co administered with P-gp inhibitors (non-ionic surfactants) in vitro and in vivo . The aim of the present study was thus to investigate if different non-ionic surfactants would have a similar effect on the in vitro and in vivo absorption of doxorubicin. This was investigated in vitro in Caco-2 cells and by oral co administration of doxorubicin together with tween 20 to male Sprague Dawley rats. 200 MUM (0.025%) tween 20 increased the intestinal absorptive permeability of doxorubicin in vitro by 48 +/- 4% from 8.8 * 10(-6)cm/s to 13.0 * 10(-6)cm/s. Further, the efflux ratio was reduced from 2.2 +/- 0.06 to 1.2 +/- 0.03 (n=3-7). In vivo, co-administration of doxorubicin and 0-25% tween 20 did not yield detectable doxorubicin plasma concentrations, probably due to extensive intestinal metabolism. In conclusion, the present study demonstrated that non ionic surfactants increased the transport of doxorubicin in vitro, most likely by inhibition of the efflux activity. However, this effect was not transferable to the in vivo situation. PMID- 26685729 TI - Clinical correlates and prognostic values of pseudoinfarction in cardiac light chain amyloidosis. AB - BACKGROUND: Pseudoinfarction is one of the most common electrocardiographic characteristics in cardiac light-chain (AL) amyloidosis. The aim of the present study was to analyze the prognostic significance of pseudoinfarction and define the relation between pseudoinfarction and clinical parameters in cardiac AL amyloidosis. METHODS: A total 110 consecutive patients who presented with a diagnosis of cardiac AL amyloidosis and without a positive history of coronary disease between 2010 and 2014 were enrolled. Patients were divided into two groups according to the presence (n=40) or absence (n=70) of pseudoinfarction on electrocardiography (ECG). Clinical parameters including laboratory tests, echocardiography, and follow-up were collected and analyzed. RESULTS: Patients with pseudoinfarction had higher N-terminal pro-brain natriuretic peptide levels (9131pg/ml vs 4644pg/ml, p=0.02) and a worse New York Heart Association (NYHA) function (p<0.001). The pseudoinfarction group also had a larger left atrium size (44mm vs 41mm, p=0.03), a thicker ventricular wall (septum 14mm vs 13mm, p=0.005 and posterior wall 14mm vs 13mm, p=0.01), a lower left ventricular ejection fraction (50% vs 58%, p=0.013), and higher early-to-atrial transmitral flow velocity ratio (p=0.001). Also, the pseudoinfarction group was closely associated with a lower voltage (70% vs 38.6%, p=0.002), poor precordial R wave progression (78.4% vs 43.9%, p=0.001), lower Sokolow-Lyon index (13mm vs 9mm, p<0.001), and lower voltage to mass ratio (0.521 vs 0.442, p=0.028) on the ECG. After a median follow-up of 39 months, Kaplan-Meier survival analysis showed that lifetime was significantly shorter in the pseudoinfarction group (median 4 months vs 17 months, p<0.001). By adopting the multivariate Cox proportional model, NYHA heart failure III to IV and the presence of pseudoinfarction remained the only two independent prognostic determinants with death hazard ratio of 3.16 and 1.9, respectively. CONCLUSIONS: The presence of pseudoinfarction on the ECG has a negative prognostic effect on AL patients with cardiac involvement. PMID- 26685730 TI - Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation. AB - BACKGROUND: Although an increased epicardial adipose tissue (EAT) volume around the left atrium (LA) is related to the atrial fibrillation (AF) burden, the role of EAT inflammation in AF is unclear. We investigated the association between AF and inflammation of the EAT around the LA. METHODS: We retrospectively identified regions of EAT around the LA and measured the density of these areas using computed tomography (CT). RESULTS: A total of 32 patients who underwent their first catheter ablation for paroxysmal AF (PAF) were enrolled (mean age 62.5+/ 11.1 years). Patients without a history of AF (n=32), but who underwent cardiac CT and were matched by age, sex, and metabolic risk factors, were enrolled in the control group (62.2+/-12.1 years). The mean EAT density around the LA was significantly higher in the PAF group than in the control group (-108.1+/-6.7 vs. -111.6+/-5.5 Hounsfield units; p=0.02), while the densities of subcutaneous adipose tissue (SAT) in the abdomen and thorax did not differ between the two groups. In a multiple logistic regression analysis, a higher EAT density was significantly associated with the presence of PAF after adjusting for other risk factors (odds ratio: 1.25; 95% confidence interval: 1.08-1.45, p=0.003). CONCLUSIONS: This study supports the hypothesis that inflammation of EAT around the LA, but not SAT, is related to the presence of PAF. PMID- 26685731 TI - Structure-Activity Relationship of Azaindole-Based Glucokinase Activators. AB - 7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds. PMID- 26685746 TI - Hybrid robust model based on an improved functional link neural network integrating with partial least square (IFLNN-PLS) and its application to predicting key process variables. AB - In this paper, a hybrid robust model based on an improved functional link neural network integrating with partial least square (IFLNN-PLS) is proposed. Firstly, an improved functional link neural network with small norm of expanded weights and high input-output correlation (SNEWHIOC-FLNN) was proposed for enhancing the generalization performance of FLNN. Unlike the traditional FLNN, the expanded variables of the original inputs are not directly used as the inputs in the proposed SNEWHIOC-FLNN model. The original inputs are attached to some small norm of expanded weights. As a result, the correlation coefficient between some of the expanded variables and the outputs is enhanced. The larger the correlation coefficient is, the more relevant the expanded variables tend to be. In the end, the expanded variables with larger correlation coefficient are selected as the inputs to improve the performance of the traditional FLNN. In order to test the proposed SNEWHIOC-FLNN model, three UCI (University of California, Irvine) regression datasets named Housing, Concrete Compressive Strength (CCS), and Yacht Hydro Dynamics (YHD) are selected. Then a hybrid model based on the improved FLNN integrating with partial least square (IFLNN-PLS) was built. In IFLNN-PLS model, the connection weights are calculated using the partial least square method but not the error back propagation algorithm. Lastly, IFLNN-PLS was developed as an intelligent measurement model for accurately predicting the key variables in the Purified Terephthalic Acid (PTA) process and the High Density Polyethylene (HDPE) process. Simulation results illustrated that the IFLNN-PLS could significant improve the prediction performance. PMID- 26685747 TI - Chloride accelerated Fenton chemistry for the ultrasensitive and selective colorimetric detection of copper. AB - A highly selective, ultrasensitive (visual and instrumental detection limits of 40 nM and 0.1 nM, respectively), environmentally-friendly, simple and rapid colorimetric sensor was developed for the detection of copper(II) in water. This sensor is based on a novel signal-amplification mechanism involving reactive halide species (RHSs) including chlorides or bromides, which accelerate copper Fenton reactions oxidizing the chromogenic substrate to develop colour. The results of this study expand our understanding of copper-based Fenton chemistry. PMID- 26685748 TI - Viral pathogenesis: Stressing out over herpes. PMID- 26685749 TI - Microbial ecology: Do it yourself nitrification. PMID- 26685751 TI - The nature of the silicaphilic fluorescence of PDMPO. AB - PDMPO (2-(4-pyridyl)-5-((4-(2 dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole), has unique silica specific fluorescence and is used in biology to understand biosilicification. This 'silicaphilic' fluorescence is not well understood nor is the response to local environmental variables like solvent and pH. We investigated PDMPO in a range of environments: using UV-vis and fluorescence spectroscopy supported by computational data, (SPARC, molecular dynamics simulations, density functional theory calculations), dynamic light scattering and zeta potential measurements to understand the PDMPO-silica interaction. From absorption data, PDMPO exhibited a pKa of 4.20 for PDMPOH2(2+) to PDMPOH(+). Fluorescence emission measurements revealed large shifts in excited state pKa* values with different behaviour when bound to silica (pKa* of 10.4). PDMPO bound to silica particles is located in the Stern layer with the dye exhibiting pH dependent depolarising motion. In aqueous solution, PDMPO showed strong chromaticity with correlation between the maximum emission wavelength for PDMPOH(+)* and dielectric constant (4.8-80). Additional chromatic effects were attributed to changes in solvent accessible surface area. Chromatic effects were also observed for silica bound dye which allow its use as a direct probe of bulk pH over a range far in excess of what is possible for the dye alone (3-5.2). The unique combination of chromaticity and excited state dynamics allows PDMPO to monitor pH from 3 to 13 while also reporting on surface environment opening a new frontier in the quantitative understanding of (bio)silicification. PMID- 26685752 TI - The role of refuges in the persistence of Australian dryland mammals. AB - Irruptive population dynamics are characteristic of a wide range of fauna in the world's arid (dryland) regions. Recent evidence indicates that regional persistence of irruptive species, particularly small mammals, during the extensive dry periods of unpredictable length that occur between resource pulses in drylands occurs as a result of the presence of refuge habitats or refuge patches into which populations contract during dry (bust) periods. These small dry-period populations act as a source of animals when recolonisation of the surrounding habitat occurs during and after subsequent resource pulses (booms). The refuges used by irruptive dryland fauna differ in temporal and spatial scale from the refugia to which species contract in response to changing climate. Refuges of dryland fauna operate over timescales of months and years, whereas refugia operate on timescales of millennia over which evolutionary divergence may occur. Protection and management of refuge patches and refuge habitats should be a priority for the conservation of dryland-dwelling fauna. This urgency is driven by recognition that disturbance to refuges can lead to the extinction of local populations and, if disturbance is widespread, entire species. Despite the apparent significance of dryland refuges for conservation management, these sites remain poorly understood ecologically. Here, we synthesise available information on the refuges of dryland-dwelling fauna, using Australian mammals as a case study to provide focus, and document a research agenda for increasing this knowledge base. We develop a typology of refuges that recognises two main types of refuge: fixed and shifting. We outline a suite of models of fixed refuges on the basis of stability in occupancy between and within successive bust phases of population cycles. To illustrate the breadth of refuge types we provide case studies of refuge use in three species of dryland mammal: plains mouse (Pseudomys australis), central rock-rat (Zyzomys pedunculatus), and spinifex hopping-mouse (Notomys alexis). We suggest that future research should focus on understanding the species-specific nature of refuge use and the spatial ecology of refuges with a focus on connectivity and potential metapopulation dynamics. Assessing refuge quality and understanding the threats to high-quality refuge patches and habitat should also be a priority. To facilitate this understanding we develop a three step methodology for determining species-specific refuge location and habitat attributes. This review is necessarily focussed on dryland mammals in continental Australia where most refuge-based research has been undertaken. The applicability of the refuge concept and the importance of refuges for dryland fauna conservation elsewhere in the world should be investigated. We predict that refuge-using mammals will be widespread particularly among dryland areas with unpredictable rainfall patterns. PMID- 26685753 TI - Long-lasting pain-related behaviors in mouse chronic cystitis model induced by a single intravesical injection of hydrogen peroxide. AB - We previously established a long-lasting cystitis model by an intravesical injection of hydrogen peroxide (H2O2) into mice. In this study, we assessed the pain-related behaviors in the cystitis model. An intravesical injection of 1.5% H2O2 transiently decreased spontaneous locomotor activity at 3 h after injection, indicative of acute spontaneous pain. In contrast, licking response to a bladder distention was slowly observed as licks to the lower abdomen at 7 and 14 days after injection, which was attenuated by amitriptyline and morphine, but not by oxybutynin. These results suggest that H2O2-induced chronic cystitis model shows delayed and long-lasting painful pathological condition. PMID- 26685750 TI - Cryptococcus: from environmental saprophyte to global pathogen. AB - Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development. PMID- 26685754 TI - RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions. AB - The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ 00201894 0.1-30 MUM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 MUM this activity was usually prolonged. At higher concentrations (3-30 MUM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 MUM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID- 26685755 TI - Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin. AB - The present study investigates the potential of layer by layer coated calcium phosphate nanoparticles - for oral delivery of insulin where Vitamin B12 grafted chitosan and sodium alginate have been used as cationic and anionic polyelectrolyte respectively. The major emphasis has been given on the role Vitamin B12 conjugated chitosan as cationic polyelectrolyte (VitB12-Chi) in the delivery system. VitB12-Chi conjugate was prepared by carbodiimide reaction. The formulated VirB12-Chi-CPNPs were tested for in vitro and in vivo efficacy studies carried out in Caco-2 monolayers and diabetic rats. VitB12-Chi-CPNPs with particle size <250nm and zeta potential+32.56(+/-2.34) exhibited pH responsive insulin release at simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopy and flow cytometry studies revealed higher uptake of VitB12-Chi-CPNPs in Caco-2 monolayer in comparison to Chi-CPNPs. Further reduction in TEER supported paracellular transport of insulin because of opening of tight epithelial junctions. In vivo intestinal uptake of FITC tagged Vit-B12 Chi-CPNPs from different intestinal segments supported paracellular and receptor mediated uptake of VitB12-Chi-CPNPs. Plasma insulin and blood glucose levels were measured in diabetic rats and showed about four fold increases in insulin bioavailability and sustained hypoglycemic effects up to 12h of administration with VitB12-Chi-CPNPs in comparison to Chi-CPNPs. Results of the study revealed the potential of layer by layer nanoparticles for oral insulin delivery. The study also specifically highlighted the role of VitB12 as a pH sensitive and targeting ligand which significantly participated in enhancing insulin oral bioavailability. STATEMENT OF SIGNIFICANCE: Oral delivery of insulin is always the most desirable approach for diabetic patients however it's also the most challenging in respect to formulation development due to harsh gastrointestinal conditions. Several groups have been working from decades for oral delivery of insulin. However the beauty of this prototype formulation is that it exhibits the pH responsive behavior in natural condition of gastrointestinal tract. It resists the release of insulin at gastric condition however stimulate the release at intestinal conditions. Apart from pH responsive behavior it utilizes multiple pathways to improve the overall bioavailability of insulin including paracellular transport and receptor mediated endocytosis. PMID- 26685756 TI - Generation of a patterned co-culture system composed of adherent cells and immobilized nonadherent cells. AB - Patterned co-culture is a promising technique used for fundamental investigation of cell-cell communication and tissue engineering approaches. However, conventional methods are inapplicable to nonadherent cells. In this study, we aimed to establish a patterned co-culture system composed of adherent and nonadherent cells. Nonadherent cells were immobilized on a substrate using a cell membrane anchoring reagent conjugated to a protein, in order to incorporate them into the co-culture system. Cross-linked albumin film, which has unique surface properties capable of regulating protein adsorption, was used to control their spatial localization. The utility of our approach was demonstrated through the fabrication of a patterned co-culture consisting of micropatterned neuroblastoma cells surrounded by immobilized myeloid cells. Furthermore, we also created a co culture system composed of cancer cells and immobilized monocytes. We observed that monocytes enhanced the drug sensitivity of cancer cells and its influence was limited to cancer cells located near the monocytes. Therefore, the incorporation of nonadherent cells into a patterned co-culture system is useful for creating culture systems containing immune cells, as well as investigating the influence of these immune cells on cancer drug sensitivity. STATEMENT OF SIGNIFICANCE: Various methods have been proposed for creating patterned co culture systems, in which multiple cell types are attached to a substrate with a desired pattern. However, conventional methods, including our previous report published in Acta Biomaterialia (2010, 6, 526-533), are unsuitable for nonadherent cells. Here, we developed a novel method that incorporates nonadherent cells into the co-culture system, which allows us to precisely manipulate and study microenvironments containing nonadherent and adherent cells. Using this technique, we demonstrated that monocytes (nonadherent cells) could enhance the drug sensitivity of cancer cells and that their influence had a limited effective range. Thus, our technique is useful for recreating complex tissues in order to investigate cellular interactions involving nonadherent cells. PMID- 26685757 TI - Assessment of glutathione peroxidase-1 polymorphisms, oxidative stress and DNA damage in sensitivity-related illnesses. AB - AIMS: Oxidative stress increase is a key event for development of sensitivity related illnesses (SRIs). The aim of this work was to evaluate the influence of a genetic variant in the antioxidant enzyme glutathione peroxidase (GPx1) on oxidative stress development in SRIs. MAIN METHODS: GPx1 rs1800668 genotype, as well as glutathione, ubiquinone, and DNA damage were assessed in 34 SRI patients and 36 healthy subjects. KEY FINDINGS: Total glutathione, reduced/oxidized glutathione, and ubiquinone were significantly decreased in cases compared with controls, while DNA fragmentation was significantly increased in patients. However, these differences were not associated to GPx1 genetic background. SIGNIFICANCE: GPx1 rs1800668 polymorphism does not play a major role in SRI related oxidative stress development. PMID- 26685758 TI - Physiological parameters as a tool in the diagnosis of fibromyalgia syndrome in females: A preliminary study. AB - AIMS: Although fibromyalgia (FM) syndrome is associated with many symptoms, there is as yet no specific finding or laboratory test diagnostic of this syndrome. The physical examination and laboratory tests may be helpful in figuring out this syndrome. MATERIALS AND METHODS: The heart rate, respiration rate, body temperature (TEMP), height, body weight, hemoglobin level, erythrocyte sedimentation rate, white blood cell count, platelet count (PLT), rheumatoid factor and C-reactive protein levels and electrocardiograms (ECG) of FM patients were compared with those of control individuals. In addition, the predictive value of these tests was evaluated via receiver operating characteristic (ROC) analysis. KEY FINDINGS: The results showed that the TEMP and the PLT were higher in the FM group compared with the control group. Also, ST heights in ECGs which corresponds to a period of ventricle systolic depolarization, showed evidence of a difference between the FM and the control groups. There was no difference observed in terms of the other parameters. According to the ROC analysis, PLT, TEMP and ST height have predictive capacities in FM. SIGNIFICANCE: Changes in hormonal factors, peripheral blood circulation, autonomous system activity disorders, inflammatory incidents, etc., may explain the increased TEMP in the FM patients. The high PLT level may signify a thromboproliferation or a possible compensation caused by a PLT functional disorder. ST depression in FM patients may interrelate with coronary pathology. Elucidating the pathophysiology underlying the increases in TEMP and PLT and the decreases in ST height may help to explain the etiology of FM. PMID- 26685759 TI - Low-salt diet increases NO bioavailability and COX-2 vasoconstrictor prostanoid production in spontaneously hypertensive rats. AB - AIMS: The ability of dietary sodium restriction to reduce the incidence of cardiovascular mortality and improve vascular function in hypertension still remains poorly understood. The aim of this study was to observe the effects of a long period of salt restriction on the vascular reactivity of mesenteric resistance arteries of SHRs. METHODS: Male SHRs received either standard-salt diet (0.3% NaCl) or low-salt diet (0.03% NaCl) for 28weeks. Vascular reactivity was studied in mesenteric artery segments and the influence of cyclooxygenase-2 (COX-2), reactive oxygen species (ROS) and participation of the renin-angiotensin system were analyzed. KEY FINDINGS: Decreased salt intake did not affect phenylephrine-induced vasoconstriction but increased acetylcholine-induced vasodilatation and also increased the response to phenylephrine after inhibition of NO synthase by L-NAME (100MUM) and iNOS protein expression was elevated. Cyclooxygenase inhibitor indomethacin (10MUM) and COX-2 inhibitor NS 398 (1MUM) decreased the reactivity to phenylephrine in low-salt-treated group, and COX-2 protein expression was elevated in low-salt group. The effects of apocynin (10MUM); superoxide anion scavenger, tiron (1mM); hydrogen peroxide scavenger, catalase (1000UmL(-1)); and ACE and AT1 receptor blockers, enalapril (10MUM) and losartan (10MUM) on vascular reactivity were not different between two groups. The levels of AT1 protein expression were similar in both groups. SIGNIFICANCE: Low-salt diet modulates mesenteric vascular responses via increased NO bioavailability suggested by increased iNOS protein expression and vasoconstrictor prostanoid production via COX-2 pathway, in SHRs. Neither ROS nor the local renin-angiotensin system is involved in these responses. PMID- 26685760 TI - Elevations in C-reactive protein and endothelin-1 system activity in humans. AB - AIMS: C-reactive protein (CRP) is an inflammatory cytokine that has been shown to be an independent predictor of future atherothrombotic events. Hyperactivity of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by the endothelium, is linked with cardiovascular disease development and progression. ET-1 is sensitive to inflammatory stimuli, though the influence of CRP on ET-1 system activity is unknown. We tested the hypothesis that ET-1-mediated vasoconstrictor tone is enhanced in adults with elevated plasma CRP concentrations. MATERIALS AND METHODS: Sixty non-obese adults (43-70years) were studied: 20 with hsCRP<1.0mg/L (low CRP; 0.5+/-0.1mg/L); 20 with hsCRP 1.0 3.0mg/L (moderate CRP; 2.0+/-0.1mg/L); and 20 with hsCRP>3.0mg/L (high CRP; 6.3+/ 0.5mg/L). Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial infusions of ET-1 (5pmol/min for 20min) and selective ETA receptor blockade (BQ-123, 100nmol/min for 60min). KEY FINDINGS: In response to ET-1, FBF decreased ~10% in the low (-10.0+/-2.3%), moderate (-10.7+/-4.0%), and high ( 6.6+/-5.2%) CRP groups, with no significant differences between groups. Additionally, all groups demonstrated a marginal, though significant (~10%), vasodilator response to BQ-123; however, there were no differences in the FBF response to BQ-123 across CRP groups. There were no significant correlations between plasma CRP concentrations and peak FBF response to either ET-1 or BQ-123. SIGNIFICANCE: These results indicate that ET-1 system activity is not influenced by elevations in CRP. Enhanced ET-1 system activity may not be involved in the increased cardiovascular disease risk associated with elevations in plasma CRP concentrations. PMID- 26685761 TI - Comparison of catch per unit effort among four minnow trap models in the three spined stickleback (Gasterosteus aculeatus) fishery. AB - Minnow traps are commonly used in the stickleback (Gasterostidae) fishery, but the potential differences in catch per unit effort (CPUE) among different minnow trap models are little studied. We compared the CPUE of four different minnow trap models in field experiments conducted with three-spined sticklebacks (Gasterosteus aculeatus). Marked (up to 26 fold) differences in median CPUE among different trap models were observed. Metallic uncoated traps yielded the largest CPUE (2.8 fish/h), followed by metallic black nylon-coated traps (1.3 fish/h). Collapsible canvas traps yielded substantially lower CPUEs (black: 0.7 fish/h; red: 0.1 fish/h) than the metallic traps. Laboratory trials further revealed significant differences in escape probabilities among the different trap models. While the differences in escape probability can explain at least part of the differences in CPUE among the trap models (e.g. high escape rate and low CPUE in red canvas traps), discrepancies between model-specific CPUEs and escape rates suggests that variation in entrance rate also contributes to the differences in CPUE. In general, and in accordance with earlier data on nine-spined stickleback (Pungitius pungitius) trapping, the results suggest that uncoated metallic (Gee type) traps are superior to the other commonly used minnow trap models in stickleback fisheries. PMID- 26685762 TI - Retraction: Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis. PMID- 26685763 TI - Retraction: Abnormal gene expression and gene fusion in lung adenocarcinoma with high-throughput RNA sequencing. PMID- 26685764 TI - At the heart of it, blood unifies. PMID- 26685765 TI - De-escalation of treatment for acute promyelocytic leukaemia? PMID- 26685766 TI - Sweet spot for cyclophosphamide: a balancing act. PMID- 26685767 TI - Ponatinib in chronic myeloid leukaemia: ready for first-line? PMID- 26685768 TI - Conditioning regimens for refractory acute myeloid leukaemia. PMID- 26685769 TI - Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. AB - BACKGROUND: Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. METHODS: Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0 3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0.15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. FINDINGS: 124 patients were enrolled between Nov 10, 2004, and Sept 23, 2009, with data cutoff of March 15, 2012. Four (3%) patients died early. After a median follow-up of 4.2 years (IQR, 3.2-5.2), the 5 year freedom from relapse was 95% (95% CI 89-98), disease-free survival was 95% (89 98), event-free survival was 90% (83-94), and overall survival was 94% (89-97). The comparison with APML3 data showed that hazard ratios were 0.23 (95% CI 0.08 0.64, p=0.002) for freedom from relapse, 0.21 (0.07-0.59, p=0.001) for disease free survival, 0.34 (0.16-0.69, p=0.002) for event-free survival, and 0.35 (0.14 0.91, p=0.02) for overall survival. INTERPRETATION: Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukaemia reduced the risk of relapse when compared with historical controls. This improvement, together with a non-significant reduction in early deaths and absence of deaths in remission, translated into better event-free and overall survival. FUNDING: Phebra. PMID- 26685771 TI - Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. AB - BACKGROUND: Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen. METHODS: In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. Data was obtained from the European Group for Blood and Marrow Transplantation registry. The primary endpoints of the study were overall survival and leukaemia-free survival. FINDINGS: We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20% [range 5-100; IQR 10-32] in the intravenous busulfan plus cyclophosphamide group vs 16% [5-95; 9-33] in the cyclophosphamide plus TBI group; p=0.16). Overall survival at 2 years did not differ between the groups in the univariate analysis (31.2% [95% CI 26.8-35.5] with intravenous busulfan plus cyclophosphamide vs 33.4% [28.1-38.7] wth cyclophosphamide plus TBI; p=0.65). Leukaemia-free survival at 2 years also did not differ between groups (25.0% [95% CI 21.0-29.0] vs 28.4% [23.4-33.5]; p=0.47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0.99 [95% CI 0.83-1.20]; p=0.95) or leukaemia-free survival (HR 0.97 [0.81-1.16]; p=0.71). Main causes of non-relapse mortality were graft versus-host disease (49 [10%] in the intravenous busulfan plus cyclophosphamide group vs 25 [7%] in the cyclophosphamide plus TBI group) and infection (36 [7%] vs 18 [5%]). INTERPRETATION: From a practical standpoint, the use of intravenous busulfan plus cyclophosphamide is likely to be a valid and efficient alternative to cyclophosphamide plus TBI conditioning regimen for patients with refractory acute myeloid leukaemia, especially for those transplant centres without access to radiation facilities. FUNDING: None. PMID- 26685772 TI - A Standard Nonmyeloablative Transplantation Regimen for Adults with Sickle Cell Disease: Are We There Yet? PMID- 26685770 TI - Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. AB - BACKGROUND: The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts. METHODS: In a multicentre phase 1-2 study, patients (aged <=65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m(2) per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417. FINDINGS: 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0.7% (credible interval 0 3.3) and 1.4% (0-4.9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively. INTERPRETATION: Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies. FUNDING: US National Heart, Lung, and Blood Institute and National Cancer Institute. PMID- 26685773 TI - Developing a Risk Prediction Model for Long-Term Physical and Psychological Functioning after Hematopoietic Cell Transplantation. AB - Hematopoietic cell transplantation (HCT) is associated with impaired physical and psychological functioning for some long-term survivors. A risk prediction model would help clinicians estimate their patients' physical and psychological functioning after HCT and determine when to refer to added supportive care when appropriate. The purpose of the present study was to develop risk prediction models for physical and psychological functioning in HCT survivors. This was a secondary analysis of data from a randomized controlled trial (NCT00799461) that included 3- to 10-year HCT survivors. Risk predictions for physical and psychological functioning were developed by using backward logistic regression. The models were internally validated using bootstrapping techniques. Regression coefficients were converted into easy-to-use risk scores. Finally, the sensitivity, specificity, and positive and negative predictive values of the total risk score were calculated. The analyses included 489 survivors, with a mean age of 45.6 (SD, 12.4) years; 47% were female and with a mean of 6.1 years (SD, 2.0) after transplantation. Younger age, higher body mass index (BMI), no or part-time work, more comorbid diseases, autologous transplantation, and chronic graft-versus-host disease predicted impaired physical functioning. Female gender, younger age, higher BMI, not living with a partner, autologous transplantation, and chronic graft-versus-host disease predicted impaired psychological functioning. Although both models had predictive value for long-term functioning, diagnostic accuracy was moderate. For the physical functioning receiver operating characteristic, area under the curve (AUC) after internal validation was .74 with sensitivity 51.9 and specificity 82.8 at the optimal cut-off. For psychological functioning, AUC after internal validation was .69 with sensitivity 83.3 and specificity 42.9 at the optimal cut-off. We conclude that it is possible to predict long-term physical and psychological functioning with readily accessible, mostly pretransplantation predictors. The accuracy of the risk prediction models can be improved for use in clinical practice, potentially by adding pretransplantation patient-reported functioning and comorbidities. PMID- 26685774 TI - A scan without evidence is not evidence of absence: Scans without evidence of dopaminergic deficit in a symptomatic leucine-rich repeat kinase 2 mutation carrier. AB - INTRODUCTION: The basis for SWEDD is unclear, with most cases representing PD mimics but some later developing PD with a dopaminergic deficit. METHODS: We studied a patient initially diagnosed with SWEDD (based on (18)F-dopa PET) who developed unequivocal PD associated with a leucine-rich repeat kinase 2 p.G2019S mutation. Repeat multitracer PET was performed at 17 years' disease duration, including (+)[11C]dihydrotetrabenazine, [11C](N,N-dimethyl-2-(2-amino-4 cyanophenylthio) benzylamine (which binds the serotonin transporter), and (18)F dopa. RESULTS: The patient showed bilateral striatal dopaminergic denervation (right putamen 28% of age-matched normal, left putamen 33%). (18)F-dopa uptake was decreased, particularly on the left (mean 31% of normal vs. 45% on the more affected right side). Serotonin transporter binding was relatively preserved in the putamen (right mean 90% of normal, left 81%) and several cortical regions. CONCLUSIONS: SWEDD can occur in genetically determined PD and may, in some cases, be the result of compensatory nondopaminergic mechanisms operating in early disease. PMID- 26685775 TI - Increased number of Campylobacter bacteraemia cases in Sweden, 2014. PMID- 26685776 TI - Electrodeposition of gold nanoparticles on aryl diazonium monolayer functionalized HOPG surfaces. AB - Gold nanoparticle electrodeposition on a modified HOPG surface with a monolayer organic film based on aryl diazonium chemistry has been studied. This organic monolayer is electrochemically grown with the use of 2,2-diphenyl-1 picrylhydrazyl (DPPH), a radical scavenger. The electrodeposition of gold on this modified surface is highly favored resulting in an AuNP surface density comparable to that found on glassy carbon. AuNPs grow only in the areas covered by the organic monolayer leaving free clean HOPG zones. A progressive mechanism for the nucleation and growth is followed giving hemispherical AuNPs, homogeneously distributed on the surface and their sizes can be well controlled by the applied electrodeposition potential. By using AFM, C-AFM and electrochemical measurements with the aid of two redox probes, namely Fe(CN)6(4 )/Fe(CN)6(3-) and dopamine, relevant results about the electrochemical modified surface as well as the gold nanoparticles electrodeposited on them are obtained. PMID- 26685777 TI - Estimation of variance and genomic prediction using genotypes imputed from low density marker subsets for carcass traits in Japanese black cattle. AB - The influence of genotype imputation using low-density single nucleotide polymorphism (SNP) marker subsets on the genomic relationship matrix (G matrix), genetic variance explained, and genomic prediction (GP) was investigated for carcass weight and marbling score in Japanese Black fattened steers, using genotype data of approximately 40,000 SNPs. Genotypes were imputed using equally spaced SNP subsets of different densities. Two different linear models were used. The first (model 1) incorporated one G matrix, while the second (model 2) used two different G matrices constructed using the selected and remaining SNPs. When using model 1, the estimated additive genetic variance was always larger when using all SNPs obtained via genotype imputation than when using only equally spaced SNP subsets. The correlations between the genomic estimated breeding values obtained using genotype imputation with at least 3,000 SNPs and those using all available SNPs without imputation were higher than 0.99 for both traits. While additive genetic variance was likely to be partitioned with model 2, it did not enhance the accuracy of GP compared with model 1. These results indicate that genotype imputation using an equally spaced low-density panel of an appropriate size can be used to produce a cost-effective, valid GP. PMID- 26685778 TI - Effects of GnRH or PGF2alpha in week 5 postpartum on the incidence of cystic ovarian follicles and persistent corpora lutea and on fertility parameters in dairy cows. AB - Resumption of ovulatory activity and the timely lysis of the first CL postpartum (pp) are important determinants for the reproductive performance of dairy cows. Cystic ovarian follicles (COFs) and persistent CLs preclude normal ovarian cyclicity and increase the calving interval. The objective of this study was to investigate the effect of GnRH on the incidence of COFs and the effect of PGF2alpha on the incidence of a prolonged luteal phase (PLP) and on fertility parameters in dairy cows. A total of 476 cows were examined ultrasonographically for the presence of a dominant follicle (12-25 mm, without CL >10 mm; n = 237) or a functional CL (>=20 mm; n = 239) between 28 and 35 days pp and were allocated to one of four groups. Cows with a dominant follicle received 10-MUg GnRH (buserelin; group F-T; n = 118) or saline (group F-C; n = 119), and cows with a functional CL received 0.5 mg of a PGF2alpha analogue (cloprostenol; group CL-T; n = 119) or saline (group CL-C; n = 120) on the day of initial examination, defined as Day 0. Cows were reexamined 7 and 21 days (F-T and F-C) and 3 and 24 days (CL-T and CL-C) later, and COFs were treated immediately after diagnosis in all cows. On the basis of the ovarian findings on Days 21 and 24, cows were treated according to a protocol aimed at timely breeding. The incidence of COFs by Days 7 (F-T vs. F-C; 7.6% vs. 16.8%) and 21 (11.0% vs. 21.8%) decreased (P <= 0.03) with GnRH; however, this did not lead to a substantial improvement of calving-to-conception interval (means +/- standard error of the mean; 107.91 +/- 5.70 vs. 117.94 +/- 6.63 days), first-service conception rate (42.3% vs. 41.3%), and number of services per conception (2.06 +/- 0.12 vs. 2.31 +/- 0.15). Treatment with PGF2alpha decreased (P < 0.0001) the incidence of PLP by Day 24 (CL-T vs. CL-C; 1.7% vs. 17.5%), decreased calving-to-conception interval(91.28 +/- 4.77 vs. 101.75 +/- 5.03 days), increased first-service conception rate (63.3% vs. 38.7%), and reduced the number of services per conception (1.65 +/- 0.10 vs. 2.08 +/- 0.12; each P <= 0.01). The results indicate that strategic treatment with GnRH or PGF2alpha in week 5 pp to induce early ovulation and luteolysis reduces the incidence of COFs and PLP, respectively. Initial treatment with PGF2alpha also enhanced reproductive performance when used in conjunction with a standardized treatment protocol for all cows in week 8 pp (aimed at timely breeding). In contrast, GnRH did not improve fertility parameters of cystic cows in herds where all cows with COFs were treated as expeditiously as possible. PMID- 26685779 TI - An Australian mixed methods pilot study exploring students performing patient risk screening. AB - Clinical placement shortages and rising costs have created demand to provide low resource, high value student learning opportunities. Malnutrition screening provides a vehicle for achieving this. A mixed methods explanatory sequential intervention study investigated time costs, and students' perceptions of preparedness after performing routine patient screening tasks, as well as students' overall views on their feelings of confidence and preparedness when commencing their first clinical placements. Pre-clinical student dietitians commencing initial placements participated (n=58), with 16 of these forming a subgroup who performed malnutrition screening tasks while the others attended usual placement orientation. The time saved when students undertook screening tasks usually assigned to nurses was substantial. Questionnaires revealed that student perceived confidence increased in the screening group when compared with controls. Focus group themes included "anxiety and confidence," "learning in the clinical learning environment," "communication skill development," and "the pre placement screening experience." Students performing routine patient-screening tasks prior to initial clinical placement has potential cost savings for healthcare organizations and was perceived to be valuable for learning. PMID- 26685780 TI - Contamination characteristics, ecological risk and source identification of trace metals in sediments of the Le'an River (China). AB - Recognizing the pollution characteristics of trace metals in river sediments and targeting their potential sources are of key importance for proposing effective strategies to protect watershed ecosystem health. In this study, a comprehensive investigation was conducted to identify the contamination and risk characteristics of trace metals in sediments of Le'an River which is a main tributary of the largest freshwater lake in China, Poyang Lake. To attain this objective, several tools and models were considered. Geoaccumulation index and enrichment factor were used to understand the general pollution characteristic of trace metals in sediments. Discriminant analysis was applied to identify the spatial variability of sediment metals. Sediment quality guidelines and potential ecological risk index were employed for ecological risk evaluation. Multivariate curve resolution-alternating least square was proposed to extract potential pollution sources, as well as the application of Monte-Carlo simulation for uncertainty analysis of source identification. Results suggested that the sediments in Le'an River were considerably polluted by the investigated trace metals (Cd, Cr, As, Hg, Pb, Cu, Zn and Ni). Sediment concentrations of these metals showed significant spatial variations. The potential ecological risk lay in high level. Comparatively speaking, the metals of Cd, Cu and Hg were likely to result in more harmful effects. Mining activities and the application of fertilizers and agrochemicals were identified as the main anthropogenic sources. To protect the ecological system of Le'an River and Poyang Lake watershed, industrial mining and agricultural activities in this area should to be strictly regulated. PMID- 26685781 TI - Cadmium uptake in above-ground parts of lettuce (Lactuca sativa L.). AB - Because of its high Cd uptake and translocation, lettuce is often used in Cd contamination studies. However, there is a lack of information on Cd accumulation in the above-ground parts of lettuce during the entire growing season. In this study, a field experiment was carried out in a Cd-contaminated area. Above-ground lettuce parts were sampled, and the Cd content was measured using a flame atomic absorption spectrophotometer (AAS). The results showed that the Cd concentration in the above-ground parts of lettuce increased from 2.70 to 3.62mgkg(-1) during the seedling stage, but decreased from 3.62 to 2.40mgkg(-1) during organogenesis and from 2.40 to 1.64mgkg(-1) during bolting. The mean Cd concentration during the seedling stage was significantly higher than that during organogenesis (a=0.05) and bolting (a=0.01). The Cd accumulation in the above-ground parts of an individual lettuce plant could be described by a sigmoidal curve. Cadmium uptake during organogenesis was highest (80% of the total), whereas that during bolting was only 4.34%. This research further reveals that for Rome lettuce: (1) the highest Cd content of above-ground parts occurred at the end of the seedling phase; (2) the best harvest time with respect to Cd phytoaccumulation is at the end of the organogenesis stage; and (3) the organogenesis stage is the most suitable time to enhance phytoaccumulation efficiency by adjusting the root:shoot ratio. PMID- 26685783 TI - Mutagenic potential of fine wastes from dimension stone industry. AB - The industrial treatment of dimension stones, such as marbles and granites, includes a stage of plate polishing, in which resins and abrasives are used, producing a fine grained waste with high moisture content. These wastes pass through decantation tanks in order to separate the solid and liquid phases. Until now, there is no knowledge about the mutagenic effects that this effluent can cause to organisms exposed to it. Thus, this study evaluated the mutagenic potential of dimension stone polishing wastes in onion root cells and fish erythrocytes. The onion seeds were germinated in Petri dishes with filter paper moistened in the liquid phase of the effluent. After germination, the onion roots were prepared for analysis of chromosomal aberrations in meristematic cells. The fishes were exposed during 72h to the solid phase of the effluent diluted in pure groundwater. Blood samples were used for counting of micronucleus and nuclear abnormalities. The onion seeds had similar germination and mitotic index in all treatments. However, it was observed in the seeds exposed to the polishing waste, numbers significantly higher of micronucleus, nuclear buds and other chromosomal aberrations when compared with the negative control. The fishes exposed to the waste showed numbers significantly higher of micronucleus when compared with the negative control. The fishes from all treatments showed significant increase in nuclear abnormalities when compared to the negative control. We concluded that the analysed wastes have mutagenic potential at the studied conditions; this effect can be related to the high content of phenolic compounds identified in the samples. PMID- 26685782 TI - Effects of the ionic liquid 1-hexyl-3-methylimidazolium bromide on root gravitropism in Arabidopsis seedlings. AB - The toxic effects of ionic liquids (ILs) have attracted increasing attention in recent years. However, the knowledge about the toxic effects of ILs on tropism in organisms remains quite limited. In this study, the effects of 1-hexyl-3 methylimidazolium bromide [C6mim]Br on root gravitropism were evaluated using Arabidopsis seedlings. Our results showed that the root growth and gravity response were significantly inhibited with increasing IL concentration. [C6mim]Br treatment affected the amount and distribution pattern of amyloplasts in root cap compared with controls. The auxin distribution marked with DR5rev::VENUS was altered in IL-treated seedlings. The signal intensity and gene expression of auxin efflux carriers PIN2 and PIN3 were obviously decreased by IL stress. Moreover, as consequences in response to gravity stimulus, the asymmetric DR5 signals in control root apex were impaired by IL treatment. The predominant PIN2 signals along the lower flank of root and PIN3 polarization in columella cells were also significantly reduced in seedlings exposed to IL. Our results suggest that the ionic liquid [C6mim]Br affects the amount and distribution of amyloplasts and disturbs the deployment of PIN2 and PIN3, thus impairing auxin flows in response to gravity stimulus and causing deficient root gravitropism in Arabidopsis seedlings. PMID- 26685784 TI - Occurrence and risk assessment of antibiotics in river water in Hong Kong. AB - The occurrence and distribution of six typical antibiotics in the main rivers of Hong Kong were investigated using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ES-MS/MS). The results revealed that the antibiotics were widely distributed in the area studied. Of the target antibiotics, ofloxacin was the most frequently detected in the rivers, with a detection rate of 69.6% and a median concentration of 0.7ng/L. Sulfadimidine (n.d-580.4ng/L) and doxycycline (n.d-82.2ng/L), with detection frequencies of 65.2% and 30.4%, respectively, were found at the same level as in rivers in North America, Spain, France, Australia, and in the Yangtze and Pearl Rivers of China, while the other target antibiotics were found at lower levels. According to the ratios of the measured environmental concentration to the predicted no-effect concentration, ofloxacin and doxycycline could present a medium to low ecological risk to algae, while sulfonamides posed no obvious ecological risk to the relevant aquatic organisms (algae, Daphnia magna, and fish). A high detection rate of antibiotics occurred in densely populated areas, revealing that population activities might be greatly contributing to the increasing levels of antibiotics in the area. Thus, the residues of antibiotics present in the waters of Hong Kong need to be closely monitored. PMID- 26685785 TI - Tissue distribution of HCH and DDT congeners and human health risk associated with consumption of fish collected from Kabul River, Pakistan. AB - Distribution of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) congeners in tissues of four different fish species and their associated potential health risks to local consumers are presented in this paper. The average ?(HCHs+DDTs) concentration in Glyptothorax punjabensis (214ngg(-1) wet weight (ww)) (carnivores) was found higher than Tor putitora (155ngg(-1) ww) (herbivores). The distribution of ?(HCHs+DDTs) in all fish tissues was found in order of liver>muscle>stomach>gills. The profile of congeners (beta-HCH/?HCH from 0.29-0.47) indicated that all selected fish species were contaminated with HCH because of its recent usage in the study area. Furthermore, DDT profile ((DDE+DDD)/?DDT from 0.61-0.78) showed that fish contamination with DDT originated from past usage and long-time degradation mechanism. The average estimated daily dietary intake of ?HCHs (15.0ngkg(-1) day(-1)) was higher than ?DDTs (12.5ngkg(-1) day(-1)) by the local consumers via fish consumption. On the basis of both 50th and 95th percentile exposure levels, the carcinogenic hazard ratios for DDT and its congeners were exceeded one (safe limit) for all fish species, indicating a great potential cancer risk for local consumers with life time consumption of contaminated fish collected from Kabul River. PMID- 26685786 TI - Effect of low-dose malathion on the gonadal development of adult rare minnow Gobiocypris rarus. AB - Malathion is an organophosphorus pesticide that extensively used in agriculture and veterinary practices. To investigate the effects of low dose malathion on rare minnow Gobiocypris rarus gonadal development, we exposed adult rare minnow to environmentally relevant concentration malathion (2 and 20MUg/L) for 21 days. Gonadal histology, sex hormone levels and mRNA expressions of steroidogenic genes were investigated. Malathion at both 2 and 20MUg/L significantly up-regulated rare minnow testicular weight and promoted the progression of spermatogenesis. Neither ovarian weight nor process of ovary development was markedly changed. In testis, 2MUg/L malathion significantly down-regulated testosterone and 11 ketotestosterone levels, and up-regulated mRNA expression of steroidogenic genes. In ovaries, 2 and 20MUg/L malathion significantly inhibited estradiol17beta levels and induced testosterone levels, both in concentration dependent manners; mRNA expressions of almost all the detected ovarian steroidogenic genes were up regulated. The present result suggested that malathion even at low dose could pose a potential threat to adult rare minnow gonadal development. PMID- 26685787 TI - Different zinc sensitivity of Brassica organs is accompanied by distinct responses in protein nitration level and pattern. AB - Zinc is an essential microelement, but its excess exerts toxic effects in plants. Heavy metal stress can alter the metabolism of reactive oxygen (ROS) and nitrogen species (RNS) leading to oxidative and nitrosative damages; although the participation of these processes in Zn toxicity and tolerance is not yet known. Therefore this study aimed to evaluate the zinc tolerance of Brassica organs and the putative correspondence of it with protein nitration as a relevant marker for nitrosative stress. Both examined Brassica species (B. juncea and B. napus) proved to be moderate Zn accumulators; however B. napus accumulated more from this metal in its organs. The zinc-induced damages (growth diminution, altered morphology, necrosis, chlorosis, and the decrease of photosynthetic activity) were slighter in the shoot system of B. napus than in B. juncea. The relative zinc tolerance of B. napus shoot was accompanied by moderate changes of the nitration pattern. In contrast, the root system of B. napus suffered more severe damages (growth reduction, altered morphology, viability loss) and slighter increase in nitration level compared to B. juncea. Based on these, the organs of Brassica species reacted differentially to excess zinc, since in the shoot system modification of the nitration pattern occurred (with newly appeared nitrated protein bands), while in the roots, a general increment in the nitroproteome could be observed (the intensification of the same protein bands being present in the control samples). It can be assumed that the significant alteration of nitration pattern is coupled with enhanced zinc sensitivity of the Brassica shoot system and the general intensification of protein nitration in the roots is attached to relative zinc endurance. PMID- 26685788 TI - Evaluation of microbial population and functional genes during the bioremediation of petroleum-contaminated soil as an effective monitoring approach. AB - This study investigated the abundance and diversity of soil n-alkane and polycyclic aromatic hydrocarbon (PAH)-degrading bacterial communities. It also investigated the quantity of the functional genes, the occurrence of horizontal gene transfer (HGT) in the identified bacterial communities and the effect that such HGT can have on biostimulation process. Illumina sequencing was used to detect the microbial diversity of petroleum-polluted soil prior to the biostimulation process, and quantitative real-time PCR was used to determine changes in the bacterial community and functional genes (alkB, phnAc and nah) expressions throughout the biostimulation of petroleum-contaminated soil. The illumine results revealed that gamma-proteobacteria, Chloroflexi, Firmicutes, and delta-proteobacteria were the most dominant bacterial phyla in the contaminated site, and that most of the strains were Gram-negative. The results of the gene expression results revealed that gram-negative bacteria and alkB are critical to successful bioremediation. Failure to maintain the stability of hydrocarbon degrading bacteria and functional gene will reduce the extend to which alkanes and PAHs are degraded. According to the results of the study, the application of a C:N:P ratio of was 100:15:1 in the biodegradation experiment resulted in the highest rate at which petroleum hydrocarbons were biodegraded. The diversity of pollutant-degrading bacteria and the effective transfer of degrading genes among resident microorganisms are essential factors for the successful biostimulation of petroleum hydrocarbons. As such, screening these factors throughout the biostimulation process represents an effective monitoring approach by which the success of the biostimulation can be assessed. PMID- 26685789 TI - Peripheral 360 Degree Retinotomy, Anterior Flap Retinectomy, and Radial Retinotomy in the Management of Complex Retinal Detachment. AB - PURPOSE: To compare the outcomes for patients with rhegmatogenous retinal detachment (RRD) and patients with retinal detachment (RD) following penetrating injury after combined 360 degree retinotomy, anterior flap retinectomy, and radial retinotomy for the management of advanced proliferative vitreoretinopathy (PVR). DESIGN: Retrospective, comparative, interventional case series. METHODS: Twenty-four eyes (60%) of 24 patients diagnosed with RRD and 16 eyes (40%) of 16 patients diagnosed with RD after penetrating injury whose surgery involved 360 degree retinotomy, anterior flap retinectomy, and radial retinotomy for the management of advanced PVR (grade D) were included in the analysis. The primary outcome was anatomic surgical success. Secondary outcomes were change in visual acuity (VA) and postoperative complications. RESULTS: The mean number of previous interventions in the RRD and trauma groups were 1.04 and 1.31, respectively (P = .13). After 51.5 (+/- 52.7) months of mean follow-up, the complete retinal reattachment rates for the RRD and trauma groups were 79% (19/24) and 75% (12/16), respectively (P > .99). The final mean VA was 2.2 logMAR (20/2000) in both groups, with improvement in the RRD group (P = .04). The most common postoperative complications in the RRD and trauma groups, respectively, were persistent hypotony in 6 eyes (25%) and 5 eyes (31%) (P = .73), corneal damage in 8 eyes (29%) and 6 eyes (38%) (P = .34), and epiretinal membrane in 5 eyes (20.8%) and 4 eyes (25%) (P > .99). CONCLUSIONS: Only 25% of the eyes (10/40) had VA of 20/200 or better. The aim of peripheral 360 degree retinotomy, anterior flap retinectomy, and radial retinotomy is to obtain retinal reattachment, which is otherwise unachievable. PMID- 26685790 TI - Long-Term Surgical Outcomes of Augmented Bilateral Lateral Rectus Recession in Children With Intermittent Exotropia. AB - PURPOSE: To compare the long-term surgical outcomes of augmented bilateral lateral rectus (LR) recession with original surgery. DESIGN: Retrospective, nonrandomized clinical study. METHODS: A total of 447 children with <=35 prism diopters (PD) of basic and divergence excess-type intermittent exotropia, who underwent original bilateral LR recession based on the largest angle measured at distance and near, or augmentation surgery with the surgical dosage augmented by 1.0-1.5 mm more than the original formula were included. Patients were observed for at least 2 years. Success rates, cumulative probabilities of success, factors related to recurrence, and overcorrection were evaluated. RESULTS: At a mean follow-up of 4.0 years, 48 of 101 patients (48%) undergoing original surgery maintained successful alignment within 10 PD of exophoria/tropia and 5 PD of esophoria/tropia; 49 (49%) had recurrence, and 3 (3%) had overcorrection. After augmented surgery, 203 of 346 patients (59%) were successfully aligned, 129 (37%) had recurrence, and 14 (4%) had overcorrection. Augmented surgery showed higher long-term successful alignment rates (P= .047) and lower recurrence rates compared to original surgery (P = .042) and the overcorrection rate was similar between the 2 groups (P= .774). Patients with divergence excess type showed higher cumulative success rates compared to that of the basic type (P = .010) after augmented surgery. CONCLUSION: Augmented bilateral LR recession resulted in more successful alignment and lower recurrence without higher overcorrection compared to the original surgery for the children with intermittent exotropia. Augmentation of the original table should be considered when planning bilateral LR recession, especially in patients with divergence excess-type exotropia. PMID- 26685791 TI - Clinical Effects and Safety of 3% Diquafosol Ophthalmic Solution for Patients With Dry Eye After Cataract Surgery: A Randomized Controlled Trial. AB - PURPOSE: To compare the efficacies and safety profiles of 3% diquafosol and 0.1% sodium hyaluronate in patients with dry eye after cataract surgery. DESIGN: Randomized controlled trial. METHODS: setting: Soonchunhyang University Hospital, Seoul, South Korea. STUDY POPULATION: In all, 130 eyes of 86 dry eye patients who had undergone cataract surgery between January 2014 and January 2015 were enrolled and randomly divided into a diquafosol group and a sodium hyaluronate group. INTERVENTION: The diquafosol group used diquafosol 6 times a day and the hyaluronate group used sodium hyaluronate 6 times a day after cataract surgery. MAIN OUTCOME MEASURES: Evaluations of efficacy were conducted based on an Ocular Surface Disease Index questionnaire, tear breakup time (TBUT), Schirmer I test, corneal fluorescein and conjunctival lissamine green staining scores, serial measurement of ocular higher-order aberrations (HOAs), corneal HOAs, and uncorrected distance visual acuity test. Safety evaluations were based on anterior chamber inflammation and discontinuation of the eye drops. RESULTS: Objective signs and subjective symptoms were aggravated at 1 week postoperatively and began to recover significantly 4 weeks after surgery. The diquafosol group showed significantly superior TBUT (P < .001), corneal fluorescein (P = .045), and conjunctival staining (P = .001) compared to the sodium hyaluronate group throughout the study period. TBUT (P < .001) and the change in HOAs (P = .018) recovered significantly more quickly in the diquafosol group. The safety evaluations showed no intergroup differences. CONCLUSIONS: Eye drops of 3% diquafosol may be an effective and safe treatment for the management of cataract surgery-induced dry eye aggravation in patients with preexisting dry eye. PMID- 26685792 TI - Do tissue spears used to clear ear canal pus improve hearing? A case series study of hearing in remote Australian Aboriginal children with chronic suppurative otitis media before and after dry mopping with tissue spears. AB - OBJECTIVE: To determine whether the use of tissue spears to remove otorrhoea from Aboriginal children's ear canals improves hearing in the affected ear. DESIGN: Case series study with controls. METHODS: The study comprised 61 Aboriginal children from communities in the remote arid zone of South Australia who had otorrhoea obscuring the tympanic membrane in 1 or both ears. Eighty ears were treated with tissue spears, and hearing was assessed before and after treatment. RESULTS: Forty-two children had unilateral and 19 had bilateral active disease. An additional 13 ears without otorrhoea served as controls. Improvement by 5 dB HL or greater in a four-frequency pure tone average occurred in 41.3 per cent of treated ears. Subsequently, blinded audiologists made qualitative judgements that a functional improvement in hearing had occurred after tissue spear use in 28.4 per cent of ears. CONCLUSION: Tissue spears can improve hearing thresholds in a significant proportion of children with otorrhoea. However, the duration of the effect is unknown. PMID- 26685793 TI - Ovine leukocyte profiles do not associate with variation in the prion gene, but are breed dependent. PMID- 26685794 TI - Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge. AB - Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ?Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. PMID- 26685795 TI - Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains. AB - Glycosylation is one of the major post-translational modifications of proteins. The status of sialylation of the neuropathological hallmarks of various neurodegenerative disorders was investigated in this study. Here, we report the novel findings that two phosphorylated tau (p-tau)-containing structures associated with Alzheimer's disease (AD), that is, neurofibrillary tangles (NFTs) and granulovacuolar degenerations (GVDs), were hypersialylated. The NFTs, GVDs and dystrophic neurites of senile plaques (SPs) in AD hippocampi were clearly visualized by immunohistochemistry using an anti-sialic acid (SA) antibody. In contrast, the amyloid core of SPs was not sialylated at all. Interestingly, other p-tau-containing structures, that is, globose-type NFTs in progressive supranuclear palsy and Pick bodies and ballooned neurons in frontotemporal lobar degeneration with Pick bodies, were also hypersialylated. Unlike the p-tau containing structures observed in tauopathies, the hallmarks of other neurodegenerative disorders, such as Lewy bodies in Parkinson's disease, glial cytoplasmic inclusions in multiple system atrophy, Bunina bodies, skein-like inclusions and round inclusions in amyotrophic lateral sclerosis, intranuclear inclusions in neuronal intranuclear inclusion disease and physiological bodies or granules (lipofuscin granules, corpora amylacea and melanin granules), were not immunolabeled by the anti-SA antibody. Because this antibody specifically identified NFTs and GVDs, immunostaining for sialylation represents a useful tool to screen these structures in a diagnostic setting. These results clearly indicate that the pathological hallmarks of various tauopathies are commonly hypersialylated, and that sialylation plays an important role in the process of p tau accumulation in AD and other tauopathies. PMID- 26685796 TI - Neural, cognitive, and evolutionary foundations of human altruism. AB - This article considers three forms of altruism from both a psychological and a neural perspective, with an emphasis on homologies that can be observed across species and potentially illuminate altruism's evolutionary origins. Kin-based altruism benefits biological relatives and, according to the theory of inclusive fitness, is ultimately beneficial to the altruist from a genetic standpoint. Kin selection adequately explains some altruistic behavior, but it is not applicable to much human altruism. Little is known about the neural processes that support it, but they may include cortical regions involved in processing autobiographical memory and the identities of familiar others. Reciprocity-based altruism is performed in expectation of future rewards and is supported by dopaminergic cortico-striatal networks that guide behavior according to anticipated rewards. Care-based altruism is aimed at improving the well-being of distressed and vulnerable individuals and is closely linked to empathic concern. This form of altruism is thought to rely on the subcortical neural systems that support parental care, particularly structures densely populated with receptors for the hormones oxytocin and vasopressin, including the amygdala, stria terminalis, and striatum. The amygdala may be a particularly important convergence point for care based altruism because of its dual role in responding both to cues that signal infantile vulnerability and those that signal distress. Research on altruism continues to converge across disciplines, but more research linking molecular level neural processes to altruistic behavior in humans and other species is needed, as is research on how various forms of altruism intersect. For further resources related to this article, please visit the WIREs website. PMID- 26685798 TI - Clinical significance of neonatal menstruation. AB - Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. PMID- 26685797 TI - The temporal topography of the N-Methyl- N-nitrosourea induced photoreceptor degeneration in mouse retina. AB - Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the progressive photoreceptors apoptosis. The N-Methyl- N nitrosourea (MNU) is an alkylating toxicant which could induce photoreceptor apoptosis resembling that of the hereditary RP. However, the detailed process pattern of this degeneration remains poorly characterized. We systemically explored the topography of the photoreceptor degeneration in the MNU treated mouse, and related these spatial data with the time-dependent characteristics of retinal pathology. These temporal topographic data delineated sequential scenes of the progressive photoreceptor degeneration in the MNU treated retinas: focal photoreceptors showed different vulnerabilities to the MNU toxicity and displayed a distinctive spatial- and time-dependent progression. Moreover, the positional asymmetry between the retinal quadrants firstly provided instructive information about the unique toxicology properties of the MNU. Further mechanism study suggested that the up-regulation of Bax and Calpain-2, rather than the Caspase-3, should be responsible for the asymmetry in the MNU induced photoreceptor degeneration. Together with the comparative sensitivities to the neurotoxicity of MNU between two photoreceptor populations, these topographic data would facilitate the standardization of analytic parameters related to the MNU induced RP model, and enhance its application in the therapeutic explorations of human RP. PMID- 26685799 TI - Rotational landmarks of the distal femur in Indian population: A MRI-based study. AB - BACKGROUND: Femoral rotational landmarks may vary according to the population. Our aim is to find out the relationship of the landmarks used in total knee arthroplasty in an Indian population and compare it with reported landmarks in other ethnic populations. MATERIALS AND METHODS: We retrospectively reviewed MR images of 124 knees in 124 patients to determine the relationship of bony landmarks by measuring the condylar twist angle (CTA), Whiteside-posterior condylar angle (W-PC), and Whiteside-epicondylar angle (W-EP). The difference between the genders and the sides was analyzed. RESULTS: The mean CTA, W-EP and W PC were 5.92 degrees , 88.99 degrees and 94.09 degrees respectively. The mean CTA, W-EP and W-PC in males were 5.77 degrees , 89.16 degrees and 94.22 degrees and they were 6.24 degrees , 88.61 degrees and 93.82 degrees in females. On the left side, the CTA, W-EP and W-PC were 5.90 degrees , 89.37 degrees and 94.45 degrees while they were 5.93 degrees , 88.65 degrees and 93.73 degrees on the right side. There was no statistically significant difference between the genders or the sides. CONCLUSION: The CTA was around 6 degrees in our study, and the posterior condylar angle (PCA) would be 3 degrees as the difference between them is 3 degrees . Hence, we conclude that the conventional jigs used in the measured resection technique using 3 degrees external rotation in reference to the posterior condyles are still an appropriate option in normal and varus knees. And there is no difference between Indians and Caucasians, but there was a significant difference with Chinese populations. Although determining rotation based on the posterior condylar axis is more practical, it is prudent to combine it with other methods. PMID- 26685800 TI - Self-instability of finite sized solid-liquid interfaces. AB - In solid-liquid systems, macroscopic solids lose their equilibrium and melt in a manner that results in overall movement of the solid-liquid interface. This phenomenon occurs when they are subjected to temperature gradients or external stress, for example. However, many experiments suggest that the melting of nano- and micro-sized metallic nuclei follows a different process not described by traditional melting theory. In this paper, we demonstrate through simulation that the melting of solid nuclei of these sizes occurs via random breaches at the interfaces. Moreover, this breaching process occurs at the exact solid-liquid equilibrium temperature and in the absence of any external disturbance, which suggests the name "self-instability" for this melting process. We attribute this spontaneous instability to the curvature of the samples; based on the relationship between the sample's instability and its curvature, we propose a destabilizing model for small systems. This model fits well with experimental results and leads to new insights into the instability behavior of small-sized systems; these insights have broad implications for research topics ranging from dendrite self-fragmentation to nanoparticle instability. PMID- 26685801 TI - Infection studies of nontarget mammalian cell lines with Bombyx mori macula-like virus. AB - Bombyx mori-derived cell lines are generally used for Bombyx mori nucleopolyhedrovirus (BmNPV)-based baculovirus expression vector system (BEVS). However, almost all of the B. mori-derived cell lines are persistently infected with Bombyx mori macula-like virus (BmMLV). In this study, nontarget mammalian cell lines were exposed to BmMLV, and their susceptibility was investigated. Real time PCR showed that viral RNA in virus-inoculated nine mammalian cell lines decreased sharply at 7 days postinfection. Also, there was no significant effect on cell viability of mammalian cells after inoculation with BmMLV. These findings indicate that mammalian cell lines used in this study are not permissive to BmMLV, and BmMLV contamination might not affect the safety aspect of BmNPV-based BEVS. PMID- 26685802 TI - MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer. AB - While progress in the treatment of advanced pancreatic cancer has accelerated in recent years, this malignancy continues to have an exceedingly poor prognosis, with no standard of care options beyond front-line chemotherapy. Currently, there are a number of new therapeutic agents in varying stages of clinical development, including molecularly targeted agents, immunotherapies, and modified versions of cytotoxics. MM-398, a novel nanoliposomal formulation of irinotecan, was designed to maximize tumor exposure while minimizing systemic toxicity due to its favorable pharmacokinetic profile. Overall, across multiple clinical trials in multiple disease indications, MM-398 has been shown to have a favorable safety and tolerability profile compared with standard irinotecan. Recent results of the Phase III NAPOLI-1 trial in patients with metastatic pancreatic cancer refractory to gemcitabine-based chemotherapy have shown a significant improvement in overall survival of MM-398 when combined with 5-fluorouracil/leucovorin, compared with 5 fluorouracil/leucovorin alone. This review focuses on the development and pharmacokinetic properties of MM-398, followed by evaluation of its safety and efficacy with a primary emphasis on clinical trials in advanced pancreatic cancer. PMID- 26685803 TI - Recruiting pro-inflammatory monocytes to ischemic injuries: On the job training required! PMID- 26685804 TI - Proteomic profiling of epileptogenesis in a rat model: Focus on inflammation. AB - Detailed knowledge about the patterns of molecular alterations during epileptogenesis is a presupposition for identifying targets for preventive or disease-modifying approaches, as well as biomarkers of the disease. Large-scale differential proteome analysis can provide unique and novel perspectives based on comprehensive data sets informing about the complex regulation patterns in the disease proteome. Thus, we have completed an elaborate differential proteome analysis based on label-free LC-MS/MS in a rat model of epileptogenesis. Hippocampus and parahippocampal cortex tissues were sampled and analyzed separately at three key time points chosen for monitoring disease development following electrically-induced status epilepticus, namely, the early post-insult phase, the latency phase, and the chronic phase with spontaneous recurrent seizures. We focused the bioinformatics analysis on proteins linked to immune and inflammatory responses, because of the emerging evidence of the specific pathogenic role of inflammatory signalings during epileptogenesis. In the early post-insult and the latency phases, pathway enrichment analysis revealed an extensive over-representation of Toll-like receptor signaling, pro-inflammatory cytokines, heat shock protein regulation, and transforming growth factor beta signaling and leukocyte transendothelial migration. The inflammatory response in the chronic phase proved to be more moderate with differential expression in the parahippocampal cortex exceeding that in the hippocampus. The data sets provide novel information about numerous differentially expressed proteins, which serve as interaction partners or modulators in key disease-associated inflammatory signaling events. Noteworthy, a set of proteins which act as modulators of the ictogenic Toll-like receptor signaling proved to be differentially expressed. In addition, we report novel data demonstrating the regulation of different Toll like receptor ligands during epileptogenesis. Taken together, the findings deepen our understanding of modulation of inflammatory signaling during epileptogenesis providing an excellent and comprehensive basis for the identification of target and biomarker candidates. PMID- 26685805 TI - Short version of the Smartphone Addiction Scale adapted to Spanish and French: Towards a cross-cultural research in problematic mobile phone use. AB - Research into smartphone addiction has followed the scientific literature on problematic mobile phone use developed during the last decade, with valid screening scales being developed to identify maladaptive behaviour associated with this technology, usually in adolescent populations. This study adapts the short version of the Smartphone Addiction Scale [SAS-SV] into Spanish and into French. The aim of the study was to (i) examine the scale's psychometric properties in both languages, (ii) estimate the prevalence of potential excessive smartphone use among Spanish and Belgian adults, and (iii) compare the addictive symptomatology measured by the SAS-SV between potentially excessive users from both countries. Data were collected via online surveys administered to 281 and 144 voluntary participants from both countries respectively, aged over 18years and recruited from academic environments. Results indicated that the reliability was excellent (i.e., Cronbach alphas: Spain: .88 and Belgium: .90), and the validity was very good (e.g., unifactoriality with a 49% and 54% of variance explained through explorative factor analysis, respectively). Findings showed that the prevalence of potential excessive smartphone use 12.5% for Spanish and 21.5% for francophone Belgians. The scale showed that at least 60% of excessive users endorsed withdrawal and tolerance symptoms in both countries, although the proposed addictive symptomatology did not cover the entire group of estimated excessive users and cultural differences appeared. This first cross-cultural study discusses the smartphone excessive use construct from its addictive pathway. PMID- 26685807 TI - Variables associated with parent satisfaction with their child's pain management. AB - OBJECTIVE: The provision of 'adequate analgesia' (which reduces the pain score by >=2 and to <4 [0-10 scale]) is significantly associated with high levels of satisfaction with pain management among adult patients. We aimed to determine the variables (including 'adequate analgesia') associated with parent satisfaction with their child's pain management. METHODS: We undertook an observational, pilot study in a mixed, metropolitan ED. Patients aged 4-16 years with a triage pain score of >=4 were enrolled. Data included demographics, presenting complaint, pain scores every 30 min, analgesia administered, time to first analgesia, provision of nurse-initiated analgesia (NIA), and 'adequate analgesia', and parent satisfaction 48-h post-discharge (6 point scale: very unsatisfied - very satisfied). RESULTS: Complete data were collected on 185 patients: mean (SD) age 10.4 (3.6) years, weight 41.9 (17.8) kg; 93 (50.3%) were male. One hundred and ten (59.4%) parents were very satisfied with their child's pain management. Children of very satisfied parents had shorter times to analgesia than those who did not (median [interquartile range] 14 (33) vs 33 (46) min, respectively, P = 0.003). Parents whose children received NIA or 'adequate analgesia' were more often very satisfied than those whose children did not. However, the differences were not significant (difference in proportions: 13.2% [95% CI -1.9, 28.3], P = 0.07 and 10.2% [95% CI -5.02, 25.34], P = 0.16, respectively). CONCLUSION: Short times to analgesia are associated with parent satisfaction. There were non significant trends towards high levels of satisfaction following the provision of NIA and 'adequate analgesia'. These findings will inform a well-powered study to confirm this association. PMID- 26685806 TI - Postmortem human brain genomics in neuropsychiatric disorders--how far can we go? AB - Large-scale collection of postmortem human brain tissue and subsequent genomic data generation has become a useful approach for better identifying etiological factors contributing to neuropsychiatric disorders. In particular, studying genetic risk variants in non-psychiatric controls can identify biological mechanisms of risk free from confounding factors related to epiphenomena of illness. While the field has begun moving towards cell type-specific analyses, homogenate brain tissue with accompanying cellular profiles, can still identify useful hypotheses for more focused experiments, particularly when the dysregulated cell types are unknown. Technological advances, larger sample sizes, and focused research questions can continue to further leverage postmortem human brain research to better identify and understand the molecular etiology of neuropsychiatric disorders. PMID- 26685809 TI - Activity and Weight Misperception among Overweight and Obese US Adults. AB - OBJECTIVES: Engaging in some exercise is associated with weight misperception (ie, overweight and obese participants self-reporting being normal weight or underweight) among adults. Less is known about associations between various types of activity with weight misperception. We examined associations between activity (moderate-vigorous leisure-time, work- and transportation-related physical activity, and sedentary activity) and weight misperception. METHODS: We used cross-sectional data from 7992 National Health and Nutrition Examination Survey 2007-2010 participants aged 20+ years with a >= 25 body mass index. Logistic regression models were used to estimate activity-weight misperception associations. RESULTS: Individuals who performed some activity, versus none, were less likely to misperceive their weight (Odds Ratio [OR]: 0.78; 95% Confidence Interval [CI]: 0.66, 0.93). Those who engaged in high levels of transportation activity were more likely to misperceive their weight (OR: 1.29; 95% CI: 1.09, 1.54). Individuals who engaged in medium and high levels of sedentary activity, versus low, were less likely to misperceive their weight (OR: 0.65; 95% CI: 0.57, 0.75 and OR: 0.51; 95% CI: 0.43, 0.61, respectively). Associations varied by sex. CONCLUSIONS: Variation in associations of various types of activity with weight misperception should be considered when developing health promotion programs. PMID- 26685810 TI - Association between Weight and Smoking Not Mediated by Weight Loss Attempts or Bullying. AB - OBJECTIVES: Youth smoking and obesity may both be mediated by weight control behaviors and experiences of bullying. This study examines associations between smoking and obesity among youth, and explores whether associations are mediated by weight loss attempts or bullying experiences. METHODS: Data from 24,173 grade 9 to 12 students in the COMPASS study (2012-13) were used to examine the prevalence of self-reported smoking, weight status, attempting to lose weight, and being a victim of bullying. Generalized linear mixed effects models were used to examine correlates of smoking. RESULTS: Among youth, 11% reported currently smoking, 20% were overweight or obese, 42% reported attempting to lose weight, and 18% reported being bullied. Girls who reported attempting to lose weight had higher odds of smoking (OR = 1.42, p = .0039), and students who reported being bullied had higher odds of smoking (OR = 1.85, p < .0001). Both variables were significantly associated with smoking independent of weight status. CONCLUSIONS: For girls, weight loss attempts were associated with smoking. For both sexes, being bullied was associated with smoking, independent of weight status. Programs attempting to reduce smoking among youth should consider the effects of weight control behaviors and bullying irrespective of weight status. PMID- 26685808 TI - The Built Food Environment and Dietary Intake among African-American Adults. AB - OBJECTIVES: The built food environment surrounding people's homes may influence their dietary intake. This exploratory study examined how the density of different sources of food in the residential environment was associated with dietary consumption among 77 African-American adults in Houston, Texas. METHODS: The number of fast-food-type restaurants, large grocery stores, and convenience type stores within 2- and 5-mile residential buffers were divided by the respective areas to obtain food environment density variables. Intake of fruit and vegetables [FV], fiber [FI], and percent energy from fat [PEF] was assessed using National Health Interview Survey items. Covariate-adjusted regressions were used to assess relations of interest. RESULTS: Greater density of fast-food-type restaurants within 2 miles was associated with greater FV, FI, and PEF (ps <= .012); and for FV and FI within 5 miles (ps <= .004). Density of large grocery stores was unrelated to intake. Greater density of convenience-type stores within 2 miles was negatively associated with FV and FI (ps <= .03); results became marginal at 5 miles for FV (p = .10) but not FI (p = .03). CONCLUSION: Maximizing healthy offerings in venue-rich metropolitan areas might provide direction for policies to reduce obesity. PMID- 26685811 TI - Linking Parental Influences and Youth Participation in Physical Activity In- and Out-of-school: The Mediating Role of Self-efficacy and Enjoyment. AB - OBJECTIVE: Parents influence their children's behavior. We examined parental influence on youth participation in physical activity (PA) in- and out-of-school, directly and/or indirectly, via self-efficacy beliefs and enjoyment of PA. METHODS: Cross-sectional analyses using self-reported data from 595 youth (Mage = 13.4 years). RESULTS: A path model linking youth perceptions of parental support and parental control to their participation in PA indirectly via self-efficacy beliefs and enjoyment of PA provided good fit to the data: chi(2)(7) = 27.63; RMSEA = .07 [90%CI = .04, .10]; CFI = .98; SRMR = .04. Perceived parental control was negatively associated with youth self-efficacy beliefs (beta = -.12, p = .01) and enjoyment of PA (beta = -.15, p = .01). Perceived tangible parental support was positively associated with self-efficacy beliefs (beta = .28, p < .01) and enjoyment of PA (beta = .13, p < .01), and perceived intangible parental support was positively associated with enjoyment of PA (beta = .18, p = .04). Self efficacy beliefs and enjoyment of PA were positively associated with participation in PA in- and out-of-school (beta = .11-.27, p <= .01). CONCLUSION: Interventions targeting parents to promote PA warrant investigation. PMID- 26685812 TI - User and Content Characteristics of Public Tweets Referencing Little Cigars. AB - OBJECTIVES: Compared to cigarettes, little cigars and cigarillos (LCC) are minimally regulated, affordable, and widely available to young people. Because Twitter is a preferred mode of communication among younger people, product portrayals may be useful for informing both interventions and public health or tobacco policy. METHODS: A mixed-methods study was implemented to analyze the content of public tweets (N = 288) and profile photos sampled from a search of 2 LCC brands (Black & Mild and Swisher Sweets). Metadata and manifest attributes of profile photo demographic features and tweet message features were coded and analyzed. Thematic analysis of the tweets was conducted using an iterative immersion/ crystallization method. RESULTS: Tweeters were most often boys or men (63%) and appeared young (76%). Prevalent content themes included expressing affiliation for the LCC product and reporting smoking activity. Although men and women tweeted affiliation for LCC products and reported smoking activity in similar numbers, women were significantly less likely to tweet about blunting than men. CONCLUSIONS: Twitter provides a potentially potent source of nuanced information about how young people are using little cigars. These observed characteristics may be useful to inform counter-messaging strategies and interventions. PMID- 26685813 TI - Using Tumblr to Reach and Engage Young Adult Smokers: A Proof of Concept in Context. AB - OBJECTIVES: To describe a proof of concept social media strategy to reach and engage young adult smokers on the social media site Tumblr. METHODS: This strategy includes creating novel, branded content, conducting proactive outreach to current and former smokers, and fostering user engagement and support within Tumblr. This social media strategy is reviewed in the context of other young adult social media-based cessation interventions and other Tumblr-based health interventions. RESULTS: Steady community growth and positive qualitative feedback constitute early indicators of impact. CONCLUSIONS: Unique challenges and limitations of data extraction from Tumblr may complicate formal evaluation efforts. Future research should consider offline or hybrid methods to mitigate these challenges. PMID- 26685814 TI - Impact of a South African School-based Intervention, HealthKick, on Fitness Correlates. AB - OBJECTIVES: To assess the impact of a whole-of-school health promotion program targeting healthy eating and physical activity on physical fitness levels, and physical activity-related knowledge, attitudes and behavior of primary school children. METHODS: Sixteen primary schools were randomly assigned as intervention (N = 8) and control (N = 8) schools. A selection of tests from the Eurofit testing battery was used to assess changes in fitness levels over the 3 years of the intervention. Anthropometric measurements included height and weight. A physical activity knowledge, attitude and behavior (KAB) questionnaire was administered to participants. Multi-level mixed effect linear models were used to assess differences between intervention and control schools. RESULTS: No overall improvement in physical fitness was found. The sit-ups score improved significantly in the intervention group (p < .05). No overall intervention effects were found on the determinants of physical activity behavior. Knowledge improved in both the intervention (p = .005) and control (p < .001) groups. CONCLUSION: The lack of a specific intervention effect on fitness levels and physical activity-related KAB indicates that a "low intensity" intervention is not effective in South African primary school settings. PMID- 26685815 TI - mHealth Pilot Study: Text Messaging Intervention to Promote HPV Vaccination. AB - OBJECTIVES: To test the feasibility and efficacy of a culturally-tailored mobile health intervention designed to increase knowledge about, intent to obtain, and receipt of the HPV vaccine. METHODS: A 7-day text message HPV intervention was developed using a quasi-experimental research design for 30 Korean-American women. RESULTS: Participants demonstrated significant increases in knowledge of HPV with an intent to get vaccinated within one year, and 30% of participants received the first dose of the HPV vaccine. CONCLUSIONS: Mobile health technology could be a promising tool in reducing the cancer burden for underserved populations. PMID- 26685816 TI - Sleep and Substance Use among US Adolescents, 1991-2014. AB - OBJECTIVES: To examine associations between sleep and alcohol, amphetamine, cigarette, marijuana, and non-heroin narcotic use among US middle and high school students, trends in associations over time, and the comparative impact of select covariates on association strength. METHODS: Data from the 1991-2014 nationally representative Monitoring the Future study of 8(th)-, 10(th)-, and 12(th)-grade US students were used to estimate standardized correlations between the frequency of getting at least 7 hours of sleep (7+ sleep) and substance use frequency while simultaneously regressing both outcomes on key covariate domains. RESULTS: As 7+ sleep frequency increased, substance use frequency significantly decreased and vice versa. Overall, association strength was inversely associated with grade. Associations were generally modest, varied across substances, and weakened over the historical period examined for 8(th)- and 10(th)- graders. Associations showed little variance by sex and racial/ethnic subgroups. Controlling for deviance, psychosocial and general health covariates significantly attenuated association strength. CONCLUSIONS: Among US secondary students, 7+ sleep/substance use associations were largely explained by individual deviance, psychosocial, and general health characteristics. Awareness and exploitation of these shared associations may be useful in improving substance use prevention and/or treatment efforts. PMID- 26685817 TI - Latino Mothers' Cumulative Food Insecurity Exposure and Child Body Composition. AB - OBJECTIVES: To document whether an intergenerational transmission of food insecurity is occurring by assessing low-income foreign-born Latino mothers' experiences with food insecurity as none, once (either childhood or adulthood) or twice (during both childhood and adulthood). Also the association between maternal cumulative food insecurity and children's body composition was examined. METHODS: Maternal self-reported surveys on retrospective measures of food insecurity during childhood, current measures of food insecurity, and demographics were collected from Houston-area community centers (N = 96). Children's body mass index (BMI) and waist circumference (WC) were directly assessed. Covariate-adjusted logistic regression models analyzed the association between cumulative food insecurity experiences and children's body composition. RESULTS: Fifty-eight percent of mothers experienced food insecurity both as a child and as an adult and 31% of the mothers experienced food insecurity either as a child or adult. Maternal cumulative exposure to food insecurity was unrelated to BMI but was negatively related to elevated WC. CONCLUSIONS: Although an intergenerational transmission of food insecurity does exist, maternal cumulative exposure to food insecurity does not impact children's body composition negatively in the short term. Studying the long-term effects of cumulative food insecurity exposure can provide information for the development and timing of obesity interventions. PMID- 26685818 TI - Comprehensive School Physical Activity Programming and Classroom Behavior. AB - OBJECTIVES: The purpose of this study was to examine the effect of a comprehensive school physical activity program (CSPAP) on classroom behavior in low-income children. METHODS: The participants included 1460 children recruited from 3 low-income schools receiving governmental financial assistance. A total of 77 classrooms were observed across grades K through 6. Classrooms were observed one week prior to the implementation of CSPAP and at 6 weeks and 12 weeks after commencement of the program. Members of the research team observed classroom behavior using systematic observation, specifically a 5-second momentary time sampling procedure. A generalized linear mixed effects model was used to determine the change in odds of a classroom achieving at least 80% on-task behavior following the implementation of CSPAP. RESULTS: There were 7.49 (95% CI: 2.83, 19.79) greater odds of a classroom achieving 80% on-task behavior at 6 weeks compared to baseline and a 27.93 (95% CI: 7.93, 98.29) greater odds of a classroom achieving 80% on-task behavior at 12 weeks compared to baseline (p < .001). CONCLUSIONS: After the CSPAP was implemented, on-task classroom behavior significantly improved across all grade levels. PMID- 26685819 TI - E-cigarette Dual Users, Exclusive Users and Perceptions of Tobacco Products. AB - OBJECTIVES: We examined differences in the characteristics of youth non-users, cigarette-only, e-cigarette-only, and dual e-cigarette and cigarette users. METHODS: Using weighted, representative data, logistic regression analyses were conducted to examine differences in demographic characteristics and tobacco use behaviors across tobacco usage groups. Multiple linear regression analyses were conducted to examine differences in harm perceptions of various tobacco products and perceived peer use of e-cigarettes by tobacco usage group. RESULTS: Compared to non-users, dual users were more likely to be white, male, and high school students. Dual users had significantly higher prevalence of current use of all products (except hookah) than e-cigarette-only users, and higher prevalence of current use of snus and hookah than the cigarette-only group. Dual users had significantly lower harm perceptions for all tobacco products except for e cigarettes and hookah as compared to e-cigarette-only users. Dual users reported higher peer use of cigarettes as compared to both exclusive user groups. CONCLUSION: Findings highlight dual users' higher prevalence of use of most other tobacco products, their lower harm perceptions of most tobacco products compared to e-cigarette-only users, and their higher perceived peer use of cigarettes compared to exclusive users. PMID- 26685820 TI - Is Adolescent Poly-tobacco Use Associated with Alcohol and Other Drug Use? AB - OBJECTIVES: To examine associations between current multiple tobacco product use, and current use of alcohol and marijuana, binge drinking, and lifetime use of marijuana, alcohol, and other drugs among US high school students. METHODS: Using 2013 Youth Risk Behavior Survey data (N = 13,583 high school students), logistic regression analyses were conducted to determine if single tobacco product or multiple tobacco product users are more likely to engage in other risk behaviors than zero tobacco product users, controlling for demographic variables. RESULTS: Overall, 23% of the sample used tobacco products and 10% of students reported current use of at least 2 tobacco products. Among single tobacco product users, the odds for engaging in risk behaviors ranged from 3.3 to 9.9 compared to non tobacco users (p < .0001). Among multiple tobacco product users, the odds ranged from 1.5 to 4.7 (p < .01) compared to single tobacco product users. CONCLUSIONS: Results suggest dual users are significantly more likely to engage in risk behavior than non-users and single product users. Future interventions should consider identifying dual-users as at higher risk, and targeting multiple risk behaviors. PMID- 26685821 TI - Comparing GPS, Log, Survey, and Accelerometry to Measure Physical Activity. AB - OBJECTIVES: We explored how objectively measured global positioning system (GPS) and accelerometer data match with travel logs and questionnaires in predicting trip duration and physical activity (PA). METHODS: 99 participants wore GPS devices and accelerometers, and recorded all trips in a log for 5 consecutive days. Participants also completed a self-administered questionnaire on PA and travel behaviors. RESULTS: There was good agreement between GPS and log for assessment of trip duration, although log measures overestimated trip duration (concordance correlation coefficient 0.53 [0.47, 0.59]; Bland-Altman estimate 0.76 [0.16, 3.71] comparing GPS to log). Log measures underestimated light PA and overestimated moderate PA compared to accelerometry when greater than zero moderate PA was reported. CONCLUSIONS: It is often not feasible to deploy accelerometry or GPS devices in population research because these devices are expensive and require technical expertise and data processing. Questionnaires and logs provide inexpensive tools to assess PA and travel with reasonable concordance with objective measures. However, they have shortcomings in evaluating the presence and amount of light and moderate PA. Future questionnaires and logs should be developed to evaluate sensitivity to light and moderate PA. PMID- 26685823 TI - Differential Effects of Social Networks on Mammography Use by Poverty Status. AB - OBJECTIVES: This study examines whether social networks have differential effects on mammography use depending on poverty status. METHODS: Data were analyzed on US women (40+), employing logistic regression and simple slope analyses for a post hoc probing of moderating effects. RESULTS: Among women not in poverty, living with a spouse/partner and attending church, regardless of frequency, were positively associated with mammography use; family size was negatively associated. Among women living in poverty, mammography showed a positive association only with weekly church attendance. Mammography was negatively associated with health-related social interactions occurring through the Internet. Post hoc probing showed significant moderating effects of poverty on the relationship between online health-related interactions and mammography use. CONCLUSIONS: To make the Internet a meaningful health empowerment tool for women in poverty, future research should identify how health-related interactions that occur online affect women in poverty's psychological and behavioral reactions that will contribute to our understanding of why they are discouraged from having mammograms. The mechanisms behind the differential effects of church attendance and poverty status on mammography also need further clarification. PMID- 26685822 TI - Racial Discrimination and HIV-related Risk Behaviors in Southeast Louisiana. AB - OBJECTIVES: We examined the relationship between cumulative experiences of racial discrimination and HIV-related risk taking, and whether these relationships are mediated through alcohol use among African Americans in semi-rural southeast Louisiana. METHODS: Participants (N = 214) reported on experiences of discrimination, HIV sexual risk-taking, history of sexually transmitted infection (STI), and health behaviors including alcohol use in the previous 90 days. Experiences of discrimination (scaled both by frequency of occurrence and situational counts) as a predictor of a sexual risk composite score as well as a history of STI was assessed using multivariate linear and logistic regression, respectively, including tests for mediation by alcohol use. RESULTS: Discrimination was common in this cohort, with respondents confirming their experience on average 7 of the 9 potential situations and on more than 34 separate occasions. After adjustment, discrimination was significantly associated with increasing sexual risk-taking and lifetime history of STI when measured either by frequency of occurrence or number of situations, although there was no evidence that these relationships were mediated through alcohol use. CONCLUSIONS: Cumulative experiences of discrimination may play a significant role in sexual risk behavior and consequently increase vulnerability to HIV and other STIs. PMID- 26685824 TI - A pH-responsive folate conjugated magnetic nanoparticle for targeted chemo thermal therapy and MRI diagnosis. AB - Polyacrylic acid functionalized Fe3O4 nanoparticles (PAA-MNPs) of average size of 10 nm are prepared by a simple soft chemical approach. These PAA-MNPs are conjugated with folic acid through peptide bonding between the carboxylic group on the surface of PAA-MNPs and the amine group of folic acid. The good colloidal stability of FA conjugated MNPs makes it a promising candidate for targeted drug delivery, hyperthermia and as a MRI contrast agent with a transverse relaxivity R2 value of 105 mM(-1) s(-1). Folic acid conjugated magnetic nanoparticles (FA MNPs) achieved ~ 95% loading efficiency of doxorubicin (DOX) which could be due to strong electrostatic interaction of highly negatively charged FA-MNPs and the positively charged DOX. The drug release study shows a pH-dependent behavior and is higher in acidic pH (4.3 and 5.6) as compared to the physiological pH (7.3). Flow cytometry and confocal microscopic image analysis reveal that around 75-80% of HeLa cells undergo apoptosis due to DNA disintegration upon incubation with DOX-MNPs for 24 h. DOX-MNPs exhibit the synergistic effect due to the combination of DOX induced apoptosis and magnetic hyperthermia treatment (MHT) which enhance the cell death ~ 95.0%. Thus, this system may serve as a potential pH sensitive nanocarrier for synergistic chemo-thermal therapy as well as a possible MRI contrast agent. PMID- 26685825 TI - Multilevel analysis quantifies variation in the experimental effect while optimizing power and preventing false positives. AB - BACKGROUND: In neuroscience, experimental designs in which multiple measurements are collected in the same research object or treatment facility are common. Such designs result in clustered or nested data. When clusters include measurements from different experimental conditions, both the mean of the dependent variable and the effect of the experimental manipulation may vary over clusters. In practice, this type of cluster-related variation is often overlooked. Not accommodating cluster-related variation can result in inferential errors concerning the overall experimental effect. RESULTS: The exact effect of ignoring the clustered nature of the data depends on the effect of clustering. Using simulation studies we show that cluster-related variation in the experimental effect, if ignored, results in a false positive rate (i.e., Type I error rate) that is appreciably higher (up to ~20-~50 %) than the chosen [Formula: see text] level (e.g., [Formula: see text] = 0.05). If the effect of clustering is limited to the intercept, the failure to accommodate clustering can result in a loss of statistical power to detect the overall experimental effect. This effect is most pronounced when both the magnitude of the experimental effect and the sample size are small (e.g., ~25 % less power given an experimental effect with effect size d of 0.20, and a sample size of 10 clusters and 5 observations per experimental condition per cluster). CONCLUSIONS: When data is collected from a research design in which observations from the same cluster are obtained in different experimental conditions, multilevel analysis should be used to analyze the data. The use of multilevel analysis not only ensures correct statistical interpretation of the overall experimental effect, but also provides a valuable test of the generalizability of the experimental effect over (intrinsically) varying settings, and a means to reveal the cause of cluster-related variation in experimental effect. PMID- 26685826 TI - [Quantitative Analysis of Wall Shear Stress for Human Carotid Bifurcation at Cardiac Phases by the Use of Phase Contrast Cine Magnetic Resonance Imaging: Computational Fluid Dynamics Study]. AB - PURPOSE: Detailed strategy for regional hemodynamics is significant for knowledge of plaque development on vascular diseases such as atherosclerosis. The aim of this study was to derive relation between atherosclerosis and hemodynamics at human carotid bifurcation by the use of computational fluid dynamics (CFD), and to provide more accurate hemodynamic information. METHODS: Blood velocity datasets at common carotid artery were obtained by phase-contrast cine magnetic resonance imaging (PC cine MRI). Carotid bifurcation model was computed for systolic, mid-diastolic, and end-diastolic phase. Comparison of wall shear stress (WSS) was performed for each cardiac phase. RESULTS: PC cine MRI provided velocity measurement for common carotid artery with various cardiac phases. The blood velocity had acute variation from 0.21 m/s to 1.07 m/s at systolic phase. The variation of WSS during cardiac phase was presented at carotid bifurcation model. High shear stress area was observed at dividing wall for all cardiac phases. The systole-diastole WSS ratio was 10.15 at internal carotid side of bifurcation. And low shear stress (<0.5 Pa) was observed at internal carotid side of bifurcation. CONCLUSION: Bifurcation area represented low shear stress and changed significantly WSS. The specific area with significant change in shear stress and low shear stress had good agreement with predilection sites of atherosclerosis. The result suggested that hemodynamics was related to atherosclerosis, and CFD analysis with various cardiac phases that were provided by PC cine MRI was allowed to determine an accurate analysis condition. This led to the representation of hemodynamics in vivo. PMID- 26685827 TI - [Isotropic Evaluation of Streak Artifact Using Extreme Value Statistical Analysis]. AB - Previous studies have shown that extreme value statistics are useful for quantitative evaluations of streak artifacts on multi-detector computed tomography (MDCT). However, we hypothesized that the scanning direction of the extreme value would affect the quantitative value obtained using the conventional method. In this study, we developed the region of interest rotation method and calculating the extreme value, and we investigated the usefulness of this method in comparison with the conventional approach. For our examination, the high absorber was placed around a water phantom and a head and chest phantom. In the new method, linearity was confirmed in the Gumbel plot of all the phantoms. On the other hand, the value of the location parameter was significantly different according to the scanning direction with the conventional method. In conclusion, compared to the conventional method, the isotropic method of evaluation does not depend on the direction of streak artifact occurrence in the new method. PMID- 26685828 TI - [Motion Analysis of Lumbar Spine and Hip Joint on Sequential Radiographs Acquired with a Dynamic Flat-panel Detector (FPD) System]. AB - PURPOSE: To design an evaluation method for lumbar spine and hip joint function using dynamic radiography using a flat-panel detector (FPD) system. METHOD: Sixteen healthy subjects (males; age range, 22-60 years; median, 27 years) and 9 patients (7 males and 2 females; age range, 67-85 years; median, 73 years) with L4 degenerative spondylolisthesis were examined using a dynamic FPD system (CANON Inc.). Sequential images were captured with the subjects in the standing position with maximal forward bending followed by backward bending for 10 s. The lateral lumbar radiographs were obtained at 2 frames/s (fps). The flexion-extension angles of L1 and S1 were measured on those images. RESULTS AND DISCUSSION: The range of motion (ROM) of the lumbar joints was significantly larger in the healthy group (82.4 +/- 8.7 degrees ) than in the disease group (50.4 +/- 8.5 degrees ; p<0.05). The ROM of the pelvic region was significantly smaller in the healthy group (26.9 +/- 17.1 degrees ) than in the disease group (53.1 +/- 17.6 degrees ; p<0.05). The healthy subjects exhibited a normal lumbar-pelvic rhythm. In the disease group, hip joint movements tended to be completed earlier compared with those in the healthy group. In the disease group, the loss of lumbar flexibility was compensated by an increase in hip joint motion due to the lumbar disease. CONCLUSION: The dynamic FPD system is a convenient imaging modality for the diagnosis of lumbar diseases through the assessment of locomotive function in the lumbar spine and hip joints. PMID- 26685829 TI - [Detectability of High Intensity Areas in FLAIR and Multi Shot EPI-FLAIR: Phantom Study]. AB - In magnetic resonance imaging (MRI) of brain, fast spin echo-fluid attenuated inversion recovery (FSE-FLAIR) is widely used to detect high intensity areas (HIAs). The way of getting FLAIR contrast at high speed includes echo planar imaging-FLAIR (EPI-FLAIR), and in EPI-FLAIR there are single shot EPI-FLAIR (SS EPI-FLAIR) and multi shot EPI-FLAIR (MS-EPI-FLAIR). There were negative opinions for the reports of SS-EPI-FLAIR, and it is reported that SS-EPI-FLAIR is able to acquire image quality that is equal to FSE-FLAIR in a shorter time, recently. But there are few reports that utilized contrast of MS-EPI-FLAIR. Our object was to compare HIA detectability in FSE-FLAIR and MS-EPI-FLAIR in equal imaging time, and to evaluate a basic characteristic. We dissolved indigestive dextrin in the aqua destillata and created a 0-46 wt% phantom. The concentration that correspond to T1, T2 value of brain white matter was 42 wt%. We calculated contrast by using signal intensities of each phantom, and compared contrast by signal intensities of each phantom, and compared the contrast of MS-EPI-FLAIR and FSE-FLAIR. In the range of 18-46 wt%, the contrast of MS-EPI-FLAIR was positive value, and that of FSE-FLAIR was 26-42 wt%. By the statistical test, contrast of MS-EPI-FLAIR in 18 26% was significantly different for FSE-FLAIR. In conclusion, it was suggestive that MS-EPI-FLAIR is able to detect HIA equally or sharply. PMID- 26685830 TI - [Analysis of Scattered Radiation in an Irradiated Body by Means of the Monte Carlo Simulation: Variation of the Subjective Contrast Due to Difference in the Location of Inhomogeneous Region]. AB - When an inhomogeneous medium such as bone, whose composition or density are clearly different from that of soft tissue of human body, exist in irradiated body, a subjective contrast of X-ray image changes by the location of these inhomogeneous medium. This cause due to the change of behavior of scattered photons in the body depends on the location of inhomogeneous medium besides due to the influence of a penumbra. But this mechanism is not explained clearly yet. In this paper, it was analyzed by means of the Monte Carlo simulation that what kind of difference occurs to a subjective contrast by the difference in location of inhomogeneous medium in water phantom and that a change in behavior of scattered photons in the phantom influences a subjective contrast by what kind of mechanism. In this case the inhomogeneous medium is bone, whose effective atomic number and density are higher than that of water, the subjective contrast of X ray image degrades when bone is located near the entrance surface (upper position) than located near the exit surface (lower position). This is caused by the number of scattered photons, originated in primary photons incident upon the zone besides the region from entrance surface to exit surface including inhomogeneous medium and incident on the area of shadow of inhomogeneous medium on the image detector, is greater in case of the upper position than in case of the lower position. In the lower position, many of these scattered photons are interacted in bone located near the exit surface by the photo-electric absorption and only a small amount is incident on the image detector. PMID- 26685831 TI - [Phantom Study on Dose Reduction Using Iterative Reconstruction in Low-dose Computed Tomography for Lung Cancer Screening]. AB - We investigated dose reduction ability of an iterative reconstruction technology for low-dose computed tomography (CT) for lung cancer screening. The Sinogram Affirmed Iterative Reconstruction (SAFIRE) provided in a multi slice CT system, Somatom Definition Flash (Siemens Healthcare) was used. An anthropomorphic chest phantom (N-1, Kyoto Kagaku) was scanned at volume CT dose index (CTDIvol) of 0.50 11.86 mGy with 120 kV. For noise (standard deviation) and contrast-to-noise ratio (CNR) measurements, CTP486 and CTP515 modules in the Catphan (The Phantom Laboratory) were scanned. Radiological technologists were participated in the perceptual comparison. SAFIRE reduced the SD values by approximately 50% compared with filter back projection (FBP). The estimated dose reduction rates by SAFIRE determined from the perceptual comparison was approximately 23%, while 75% dose reduction rate was expected from the SD value reduction of 50%. PMID- 26685832 TI - [Comparison of Quantitative Value of Dopamine Transporter Scintigraphy Calculated from Different Analytical Software]. AB - In the dopamine transporter scintigraphy there are two quantitative analysis softwares, DaTView and DaTQUANT. The quantitative value of both software has to be treated independently because there is a difference between them in the point of how to set the region of interest on the striatum and the background, calculation formula of quantitation. And also DaTQUANT has a capability of performing anatomical standardization which DaTView does not have. The aim of this study was to evaluate the accuracy of registration on DaTQUANT using a phantom, and to evaluate the correlation between the quantitative values between DaTView and DaTQUANT using clinical data. As a result, the accuracy of registration was acceptable. Regardless of the degree of accumulation in the striatum, there was a high correlation to each analysis software (r>0.85). PMID- 26685833 TI - [Evaluation of Radiation Dose during Stent-graft Treatment Using a Hybrid Operating Room System]. AB - In recent years, aortic aneurysm treatment with stent graft grafting in the X-ray fluoroscopy is increasing. This is an endovascular therapy, because it is a treatment which includes the risk of radiation damage, having to deal with radiation damage, to know in advance is important. In this study, in order to grasp the trend of exposure stent graft implantation in a hybrid operating room (OR) system, focusing on clinical data (entrance skin dose and fluoroscopy time), was to count the total. In TEVAR and EVAR, fluoroscopy time became 13.40 +/- 7.27 minutes, 23.67 +/- 11.76 minutes, ESD became 0.87 +/- 0.41 mGy, 1.11 +/- 0.57 mGy. (fluoroscopy time of EVAR was 2.0 times than TEVAR. DAP of EVAR was 1.2 times than TEVAR.) When using the device, adapted lesions and usage are different. This means that care changes in exposure-related factors. In this study, exposure trends of the stent graft implantation was able to grasp. It can be a helpful way to reduce/optimize the radiation dose in a hybrid OR system. PMID- 26685834 TI - [The Relation between the Height of Radiographic Table and Workloads of Radiologic Technologist in General X-ray Examinations]. AB - Workloads of radiological technologists under different conditions of heights of radiographic table and/or X-ray tube assembly were calculated using a software for preventing musculoskeletal complaint to investigate optimal working environment for general X-ray examinations. In the patient positioning, compressive force of lumbar disc decreased at higher radiographic table within the range of 45-90 cm. On the other hand, workload of the shoulder joint increased with increase in the height of radiographic table. Load of the shoulder joint similarly increased as the height of the X-ray tube assembly increased. Compressive force of lumbar disc reduced by approximately 10-30% as the height ratio of the radiographic table to body height increased by approximately 40%, compared to the lowest table of 45 cm. Muscle load of a 50-years-old woman was approximately double compared to a 30-year-old man, even in the same workload. It is important to keep suitable height of radiographic table for reduction of the workloads of lumbar rather than shoulder joint, because floating-type radiographic table is generally used. PMID- 26685835 TI - [An Examination of Variable Image Positions in the Aortic Valve Blood Flow Using Phase Contrast MRI: Effect of Breath-holding Methods in Healthy Volunteers]. AB - Phase contrast MRI (PC-MRI) is a useful tool for evaluating valvular pathology. In addition, PC-MRI can provide a noninvasive assessment of blood flow in an arbitrary cross section. However, the blood flow measurement with breath-hold or free breath PC-MRI may be different from each other because of intrathoracic pressure changing and variable image position. The aim of this study was to find both the optimal breath-hold technique and the image position. Quantitative flow images were acquired in four planes (ascending aorta: Ao, sino-tubular junction: STJ, valsalva sinus: valsalva, left ventricular outflow tract: LVOT), in healthy subjects (n=10). The study protocol was divided into two parts: (1) stroke volume (SV) measured in each slice positions by using inspiration, expiration, and navigation method during normal breathing and (2) SV measured at each breath-hold techniques in the Ao, STJ, valsalva, and LVOT. As a result, (1) SV of the respective measurement positions were not significant by using inspiration, expiration, and navigation method and (2) LVOT SV was significantly lower than Ao, STJ, and valsalva. PMID- 26685836 TI - [Development of a Novel Body Phantom with Bone Equivalent Density for Evaluation of Bone SPECT]. AB - We developed a custom-designed phantom for bone single photon emission computed tomography (SPECT)-specific radioactivity distribution and linear attenuation coefficient. The aim of this study was to evaluate the accuracy of the phantom. The lumbar phantom consisted of the trunk of a body phantom (background) containing a cylinder (vertebral body), a sphere (tumor), and a T-shaped container (processus). The vertebral body, tumor, and processus phantoms contained a K(2)HPO(4) solution of bone equivalent density and 50, 300 and 50 kBq/mL of (99m)Tc, respectively. The body phantom contained 8 kBq/mL of (99m)Tc solution. SPECT images were acquired using low-energy high-resolution collimation, a 128 * 128 matrix and 120 projections over 360 degrees with a dwell time of 15 sec/view * 4 times. Thereafter, CT images were acquired at 130 kV and 70 ref mAs using adaptive dose modulation. The SPECT data were reconstructed with ordered subset expectation maximization with three dimensional, scatter, and CT-based attenuation correction. Count ratio, linear attenuation coefficient (LAC), and full-width at half-maximum (FWHM) were measured. Count ratios between the background, the vertebral body, and the tumor in SPECT images were 463.8: 2888.0: 15150.3 (1: 6.23: 32.7). The LAC of the background and vertebral body in the CT-derived attenuation map were 0.155 cm-1 and 0.284 cm-1, respectively, and the FWHM measured from the processus was 15.27 mm. The precise counts and LAC indicated that the phantom was accurate and could serve as a tool for evaluating acquisition, reconstruction parameters, and quantitation in bone SPECT images. PMID- 26685837 TI - [Construction of System for Support of Multifacility IVR Dose Analysis and Research]. AB - Although measurement and management of angiographic entrance skin dose (ESD) are deemed extremely important, accurate determination of maximum ESD and its location is generally difficult because of the dependence on therapeutic technique and position. Following our development of body-mounted gear bearing radiophotoluminescence glass dosimeter (RPLD) arrays for direct measurement of ESD in cranial and cardiovascular angiography and interventional radiology (IVR), our focus next turned to the limited number of facilities equipped to read RPLD outputs and the need for methods to effectively provide feedback to clinical facilities. As described here, we first constructed an RPLD reading facility capable of sending and receiving RPLDs by post, offering the potential to enable utilization of the developed gear at all hospitals in Japan that perform angiography and IVR. We next developed specialized web-based system to generate dose maps from RPLD dose data, thereby enabling any facility to perform trial system analysis, evaluation, and implementation; and investigated the results and related problems. PMID- 26685839 TI - [1. Recent Trend, Safety, Future Direction about Wireless Communications Technology]. PMID- 26685838 TI - [National Dose Standards for X-ray Diagnostics and Calibration of Dosemeters]. PMID- 26685840 TI - [Preface]. PMID- 26685841 TI - [1. Clinincal Diagnosis and Medical Care of Liver Disease, Present Situation and Progress]. PMID- 26685842 TI - [Report of Studying Abroad at Stanford University]. PMID- 26685843 TI - [Important Themes of Discussion with the Ministry of Health, Labour and Welfare]. PMID- 26685844 TI - [Human Resource Development in Schientific Society]. PMID- 26685845 TI - BoneCreo: a novel approach for generating a geometric model of the bone structure. AB - Bones, the fundamental part of the skeleton, are constantly subjected to many biological processes including growth, feeding and remodelling. Remodelling causes changes in bone structure that may be difficult to notice on a day-to-day basis but become significant over the longer time span. It acts on the cancellous and cortical bone tissue, causing alterations in thickness and spatial arrangement in the first and alternations in pore size in the second. In healthy individuals such changes are a part of the natural bone remodelling process explained by Wolff's law. However, the direction of such changes is difficult to predict in patients in various pathological states in which bone health is affected. Here, we present a method to generate a computer based geometric model of the bone structure based on the cancellous tissue structure images. As a result we obtained a geometric model of the structure corresponding to the physical model of the cancellous bone. Such a model can be used in computer simulation to predict the remodelling changes in the healthy and pathological bone structures. PMID- 26685846 TI - Reduction of phosphorus concentration in mineral supplement on fertility rate, maternal ability and costs of beef cows reared in pastures of Urochloa decumbens. AB - Manufacturing and marketing of mineral mixtures with less than 40 g kg(-1) phosphorus (P) is prohibited under Brazilian regulations, although scientific evidence rejects this recommendation. Considering the hypothesis that P levels in commercial mineral supplements can be reduced without affecting animal performance and health, the objective of this experiment was to evaluate the effects of reducing the concentration of P in the mineral supplement (from 40 to 18 g kg(-1)) of a herd of beef cows grazing tropical pastures of signal grass (Urochloa decumbens). The experiment was carried out in the savanna region of Mato Grosso do Sul, Brazil, during the years 2011 to 2013. Variables analyzed included pregnancy rate, calving interval, weight of calves at weaning, and cost of mineral supplementation. There were no changes in the reproductive parameters of the herd and the weight at weaning of the calves. However, the cost of mineral supplementation was significantly lower when the herd was supplemented with the mineral mix containing only 18 g kg(-1) P. Phosphorus concentration of the forage was analyzed monthly during 1 year and averaged 1.9 +/- 0.45 g kg(-1) DM. Thus, it appears possible to reduce P content and cost of mineral supplementation without any adverse effects on the health and productivity of beef cattle herds in the State of Mato Grosso do Sul. However, the final decision should be made based on the clinical-nutritional examination and by constant technical assistance to the farm. PMID- 26685847 TI - Morphological diversity of cultured cold-active lytic bacteriophages isolated from the Napahai plateau wetland in China. PMID- 26685848 TI - Erratum to: Prevention in kindergartens with 500 ppm fluoride toothpaste-a randomized clinical trial. PMID- 26685849 TI - Nonsurgical therapy of chronic periodontitis with adjunctive systemic azithromycin or amoxicillin/metronidazole. AB - OBJECTIVES: The objective of the present study is to compare the effect of systemic adjunctive use of azithromycin with amoxicillin/metronidazole to scaling and root planing (SRP) in a clinical study. MATERIALS AND METHODS: Data from 60 individuals with chronic periodontitis were evaluated after full-mouth SRP. Antibiotics were given from the first day of SRP, in the test group (n = 29), azithromycin for 3 days and, in the control group (n = 31), amoxicillin/metronidazole for7 days. Probing depth (PD), attachment level (AL), and bleeding on probing (BOP) were recorded at baseline and after 3 and 12 months. Gingival crevicular fluid was analyzed for matrix metalloprotease (MMP)-8 and interleukin (IL)-1beta levels. Subgingival plaque was taken for assessment of the major bacteria associated with periodontitis. RESULTS: In both groups, PD, AL, and BOP were significantly reduced (p < 0.001). A few significant differences between the groups were found; AL and BOP were significantly better in the test than in the control group at the end of the study (p = 0.020 and 0.009). Periodontopathogens were reduced most in the test group. CONCLUSIONS: A noninferiority of the treatment with azithromycin in comparison with amoxicillin/metronidazole can be stated. The administration of azithromycin could be an alternative to the use of amoxicillin/metronidazole adjunctive to SRP in patients with moderate or severe chronic periodontitis; however, a randomized placebo-controlled multicenter study is needed. CLINICAL RELEVANCE: Application of azithromycin as a single antibiotic for 3 days might be considered as an additional adjunctive antibiotic to SRP in selected patients. PMID- 26685850 TI - Assessment of postoperative pain after reciprocating or rotary NiTi instrumentation of root canals: a randomized, controlled clinical trial. AB - OBJECTIVES: The aim of this study was to assess postoperative pain in a prospective randomized clinical trial comparing two groups, using the Reciproc(r) system in one group and the ProTaper(r) rotary system in the other. MATERIAL AND METHODS: The study included 78 male patients, aged 18-64 years (mean age of 26 years), with asymptomatic pulp necrosis in mandibular molar teeth (n = 78). The single-session endodontic treatment was performed by a single operator specialized in Endodontics. Mechanical preparation of the root canals was performed using the ProTaper(r) and Reciproc(r) instrumentation techniques. Postoperative pain was recorded using a verbal rating scale (VRS) and verbal description with well-defined categories at the three following time intervals: 24 h, 72 h, and 7 days after the endodontic procedure. The assessment of postoperative pain was recorded as no pain, mild pain, moderate pain, and severe pain or flare-up. Data were analyzed using the nonparametric Mann-Whitney test with the aid of the STATA(r) software. RESULTS: The incidence of postoperative pain in the ProTaper group (PT) 24 h after the endodontic procedure was 17.9 and 5.1 % after 72 h. In the Reciproc group (RP), the incidence after 24 h was 15.3 and 2.5 % after 72 h. No patients presented severe pain at the time intervals assessed. CONCLUSIONS: No significant difference (p > 0.05) in postoperative pain was found between the ProTaper(r) and Reciproc(r) instrumentation technique during endodontic treatment in this study. CLINICAL RELEVANCE: According to our findings and the results of the clinical trial, the occurrence of postoperative pain was low and similar between the reciprocating and rotary techniques during the time intervals assessed. These results are different from basic laboratory studies that affirm that the reciprocating techniques tend to promote more postoperative pain since extrusion of debris is greater. PMID- 26685851 TI - The Role of 18F-FDG PET/CT on Staging and Prognosis in Patients with Small Cell Lung Cancer. AB - BACKGROUND: We evaluated 18F-FDG PET/CT in small cell lung cancer (SCLC) staging and assessed metabolic (SUVmax, MTV and TLG) and morphologic (CTvol) variables as predictors for overall survival (OS) and progression-free survival (PFS). METHODS: Patients with newly diagnosed, histopathology-confirmed SCLC, who underwent 18F-FDG PET/CT were evaluated. A Cox proportional hazard model was used to determine the association between the primary tumour SUVmax, MTV, TLG and CTvol with OS and PFS. Similar evaluations were performed when hilar/mediastinal lymphadenopathy was included [total SUVmax (TSUVmax), total MTV (TMTV) and total TLG (TTLG)]. RESULTS: 55 patients were included. 18F-FDG PET/CT changed staging in 6/55 (10.9%) patients who were upstaged to extensive disease. TTLG (>443.8) was a significant variable for OS with HR=2.1 (CI 1.14-3.871, p=0.017). Patients with TTLG>443.8 had a median OS of 13.4 months compared to 25.7 months in patients with TTLG<443.8 (p=0.018). TMTV (>72.4) was significant for PFS with HR=2.3 (CI 1.11-4.8, p=0.025). A median PFS of 12.1 and 26.2 months was found with TMTV greater and less than 72.4, respectively (p=0.005). CONCLUSIONS: 18F FDG PET/CT improved staging of patients with SCLC, and TTLG and TMTV can be used as prognostic variables for OS and PFS, respectively. KEY POINTS: * Identifying variables that predict the prognosis of patients with SCLC is important. * 18F FDG PET/CT influences staging of patients with SCLC. * Metabolic parameters could be used as predictors for PFS and OS. PMID- 26685853 TI - Prediction of disease progression following concurrent chemoradiotherapy for uterine cervical cancer: value of post-treatment diffusion-weighted imaging. AB - OBJECTIVE: To investigate the value of post-treatment diffusion-weighted imaging (DWI) for predicting disease progression following concurrent chemoradiotherapy (CCRT) for cervical cancer. METHODS: This retrospective study included 100 consecutive patients with locally advanced cervical cancer who underwent T2 weighted imaging (T2WI) and DWI 1 month after completing CCRT. The presence of residual tumour was independently determined on T2WI and T2WI plus DWI. The imaging findings were compared regarding prediction of disease progression. RESULTS: Disease progressed in 24 patients during follow-up. Forty-one and 22 patients were determined as having residual tumour on T2WI and T2WI plus DWI, respectively. Regarding prediction of disease progression, positive predictive values of imaging findings on T2WI and T2WI plus DWI were 32.7 % and 54.4 %, respectively, 1 year after treatment (P = 0.004), 37.2 % and 73.0 %, respectively, 2 years after treatment (P < 0.001), and 39.3 % and 72.7 %, respectively, 3 years after treatment (P = 0.001). Multivariate Cox regression analysis revealed that the presence of residual tumour on T2WI plus DWI was the independent predictor of disease progression (hazard ratio = 6.34, P < 0.001). CONCLUSION: Post-treatment DWI offers an incremental value to T2WI in predicting disease progression after CCRT of cervical cancer. KEY POINTS: * T2WI alone has limited prognostic value after CCRT of cervical cancer. * Adding DWI to T2WI improves prediction of disease progression after CCRT. * Residual tumour on post treatment T2WI plus DWI is associated with disease progression. PMID- 26685852 TI - Contrast-induced nephropathy in CT: incidence, risk factors and strategies for prevention. AB - In the past, a high percentage of hospital-acquired renal failure was attributed to contrast media. That position is now very controversial. Recently, doubts have been raised regarding the real relationship between acute kidney injury and intravenous contrast media administration. Similarly, statements about specific methods of preventing contrast-inducing nephropathy have been challenged. This review article addresses the controversies of incidence, causation, and prevention in an attempt to help the practicing radiologist adopt methods for their own department. KEY POINTS: * The reported CIN incidence ranges from 2-12 % following contrast-enhanced CT. * Studies without a non-contrast CT control group may overestimate CIN incidence. * Development and application of a comprehensive CIN prevention strategy is recommended. PMID- 26685854 TI - Process development of a human recombinant diabody expressed in E. coli: engagement of CD99-induced apoptosis for target therapy in Ewing's sarcoma. AB - Ewing's sarcoma (EWS) is the second most common primary bone tumor in pediatric patients characterized by over expression of CD99. Current management consists in extensive chemotherapy in addition to surgical resection and/or radiation. Recent improvements in treatment are still overshadowed by severe side effects such as toxicity and risk of secondary malignancies; therefore, more effective strategies are urgently needed. The goal of this work was to develop a rapid, inexpensive, and "up-scalable" process of a novel human bivalent single-chain fragment variable diabody (C7 dAbd) directed against CD99, as a new therapeutic approach for EWS. We first investigated different Escherichia coli constructs of C7 dAbd in small-scale studies. Starting from 60 % soluble fraction, we obtained a yield of 25 mg C7 dAbd per liter of bacterial culture with the construct containing pelB signal sequence. In contrast, a low recovery of C7 dAbd was achieved starting from periplasmic inclusion bodies. In order to maximize the yield of C7 dAbd, large-scale fermentation was optimized. We obtained from 75 % soluble fraction 35 mg C7 dAbd per L of cell culture grown in a synthetic media containing 3 g/L of vegetable peptone and 1 g/L of yeast extract. Furthermore, we demonstrated the better efficacy of the cell lysis by homogenization versus periplasmic extraction, in reducing endotoxin level of the C7 dAbd. For gram scale purification, a direct aligned two-step chromatography cascade based on binding selectivity was developed. Finally, we recovered C7 dAbd with low residual process-related impurities, excellent reactivity, and apoptotic ability against EWS cells. PMID- 26685855 TI - Accumulation of dibenzocyclooctadiene lignans in agar cultures and in stationary and agitated liquid cultures of Schisandra chinensis (Turcz.) Baill. AB - Schisandra chinensis plant in vitro cultures were maintained on Murashige and Skoog (MS) medium supplemented with 3 mg/l 6-benzyladenine (BA) and 1 mg/l 1 naphthaleneacetic acid (NAA) in an agar system and also in two different liquid systems: stationary and agitated. Liquid cultures were grown in batch (30 and 60 days) and fed-batch modes. In the methanolic extracts from lyophilized biomasses and in the media, quantification of fourteen dibenzocyclooctadiene lignans identified based on co-chromatography with authentic standards using high performance liquid chromatography with diode array detection (HPLC-DAD) and/or liquid chromatography with diode array detection and electrospray ionization mass spectrometry (LC-DAD-ESI-MS) methods. For comparison purposes, phytochemical analyses were performed of lignans in the leaves and fruits of the parent plant. The main lignans detected in the biomass extracts from all the tested systems were schisandrin (max. 65.62 mg/100 g dry weight (DW)), angeloyl-/tigloylgomisin Q (max. 49.73 mg/100 g DW), deoxyschisandrin (max. 43.65 mg/100 g DW), and gomisin A (max. 34.36 mg/100 g DW). The highest total amounts of lignans in the two tested stationary systems were found in extracts from the biomass harvested after 30 days of batch cultivation: 237.86 mg/100 g DW and 274.65 mg/100 g DW, respectively. In the agitated culture, the total content reached a maximum value of 244.80 mg/100 g DW after 60 days of the fed-batch mode of cultivation. The lignans were not detected in the media. This is the first report which documents the potential usefulness of S. chinensis shoot cultures cultivated in liquid systems for practical purposes. PMID- 26685856 TI - Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro. AB - Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV. PMID- 26685857 TI - A stable luciferase reporter plasmid for in vivo imaging in murine models of Staphylococcus aureus infections. AB - In vivo imaging of bioluminescent bacteria permits their visualization in infected mice, allowing spatial and temporal evaluation of infection progression. Most available bioluminescent strains were obtained by integration of the luciferase genes into the bacterial chromosome, a challenging and time-consuming approach. Recently, episomal plasmids were used, which were introduced in bacteria and expressed all genes required for bioluminescence emission. However, the plasmid was progressively lost in vitro and in vivo, if bacteria were not maintained under antibiotic selective pressure. Increased stability could be obtained inserting into the plasmid backbone sequences that assured plasmid partition between daughter bacterial cells, or caused death of bacteria that had lost the plasmid. So far, no detailed analysis was performed of either plasmid stability in vivo or contribution of different stabilizing sequence types. Here we report the construction of a plasmid, which includes the Photorhabdus luminescens lux cassette expressed under the control of a Staphylococcus aureus specific gene promoter, and toxin/antitoxin (T/A) and partition sequences (Par) conferring stability and transmissibility of the plasmid. Following infection of mice with S. aureus carrying this plasmid, we demonstrated that the promoter-lux fusion was functional in vivo, that the plasmid was retained by 70-100% of bacterial cells 7 days post-infection, and that both stabilizing sequence types were required to maximize plasmid retention. These data suggest that the plasmid can be a valuable tool to study gene expression and bacterial spread in small laboratory animals infected with S. aureus or possibly other Gram-positive human pathogens. PMID- 26685858 TI - Involvement of NADPH oxidases and non-muscle myosin light chain in senescence of endothelial progenitor cells in hyperlipidemia. AB - NADPH oxidase (NOX)-derived reactive oxygen species (ROS) is involved in endothelial dysfunction of hyperlipidemia, and non-muscle myosin regulatory light chain (nmMLC20) is reported to have a transcriptional function in regulation of gene expression. The purposes of this study are to determine whether NOX-derived ROS can promote endothelial progenitor cell (EPC) senescence and whether nmMLC20 can regulate NOX expression through a phosphorylation-dependent manner. The rats were subjected to 8 weeks of high-fat diet feeding to establish a hyperlipidemic model, which showed an increase in plasma lipids and the accelerated senescence and reduced number of circulating EPCs, accompanied by an increase in myosin light chain kinase (MLCK) and NOX activities, p-nmMLC20 level, NOX (NOX2, NOX4) expression, and H2O2 content. Next, EPCs isolated from normal rats were incubated with ox-LDL (100 MUg/mL) for 24 h to establish a senescent model in vitro. Consistent with our in vivo findings, ox-LDL treatment increased the senescence of EPCs concomitant with an increase in MLCK and NOX activities, p-nmMLC20 level (in total or nuclear proteins), NOX expression, and H2O2 content; these phenomena were reversed by MLCK inhibitor. NOX inhibitor achieved similar results to that of MLCK inhibitor except that there is no effect on MLCK activity and p-nmMLC20 level. Furthermore, knockdown of nmMLC20, NOX2, or NOX4 led to a down-regulation in NOX and a reduction in ox-LDL-induced EPC senescence. These results suggest that NOX-derived ROS promotes the senescence of circulating EPCs in hyperlipidemia and nmMLC20 may play a transcriptional role in the upregulation of NOX through a phosphorylation-dependent manner. PMID- 26685859 TI - Hearing and tinnitus in head and neck cancer patients after chemoradiotherapy. AB - Head and neck cancer patients treated with high-dose cisplatin and radiotherapy will suffer from hearing deficits. The current low-dose regimen seldom causes hearing threshold decrease. Tinnitus in this patient population has not been investigated earlier. We aimed to evaluate the possible ototoxicity of low-dose (40 mg/m(2)) weekly administered cisplatin with concomitant radiotherapy. Twenty two patients with locally advanced head and neck cancer were prospectively recruited to participate the study after treatment recommendation for chemoradiotherapy with low-dose cisplatin and intensity-modulated radiotherapy. They filled in a Tinnitus Handicap Inventory and undertook audiologic evaluations before and after treatment. Ototoxicity was determined by >10 dB threshold shift at frequencies 4 and 8 kHz or in pure tone average. A historical cohort of nine patients treated with high-dose (100 mg/m(2)) cisplatin and radiotherapy was used for comparison. After treatment, study patients demonstrated no significant changes in their hearing over frequencies 0.5-4 kHz, and the threshold shifts were minor at 4 and 8 kHz. More than 50 % of patients reported no tinnitus after treatment and the remainder only had slight to moderate tinnitus causing no interference with their daily activities. In contrast, five of the nine patients having received high-dose cisplatin reported disturbing tinnitus. Further, changes in pure tone averages were exhibited in three of these patients and six had significant threshold shifts at 4 and 8 kHz. Head and neck cancer patients treated with concomitant intensity-modulated radiotherapy and low-dose cisplatin seem to experience only minor audiological sequelae and therefore, these patients appear to require no routine audiological monitoring. Such evaluation could be performed only when needed. PMID- 26685860 TI - Identification of novel inhibitors for Pim-1 kinase using pharmacophore modeling based on a novel method for selecting pharmacophore generation subsets. AB - Targeting Proviral integration-site of murine Moloney leukemia virus 1 kinase, hereafter called Pim-1 kinase, is a promising strategy for treating different kinds of human cancer. Headed for this a total list of 328 formerly reported Pim 1 kinase inhibitors has been explored and divided based on the pharmacophoric features of the most active molecules into 10 subsets projected to represent potential active binding manners accessible to ligands within the binding pocket of Pim-1 kinase. Discovery Studio 4.1 (DS 4.1) was employed to detect potential pharmacophoric active binding manners anticipated by Pim-1 Kinase inhibitors. The pharmacophoric models were then allowed to compete within Quantitative Structure Activity Relationship (QSAR) framework with other 2D descriptors. Accordingly Genetic algorithm and multiple linear regression investigation were engaged to find the finest QSAR equation that has the best predictive power r262(2) = 0.70, F = 119.14, rLOO(2) = 0.693, rPRESS(2) against 66 external test inhibitors = 0.71 q(2) = 0.55. Three different pharmacophores appeared in the successful QSAR equation this represents three different binding modes for inhibitors within the Pim-1 kinase binding pocket. Pharmacophoric models were later used to screen compounds within the National Cancer Institute database. Several low micromolar Pim-1 Kinase inhibitors were captured. The most potent hits show IC50 values of 0.77 and 1.03 uM. Also, upon analyzing the successful QSAR Equation we found that some polycyclic aromatic electron-rich structures namely 6-Chloro-2-methoxy acridine can be considered as putative hits for Pim-1 kinase inhibition. PMID- 26685861 TI - Exposure to volatile anaesthetics is not followed by a massive induction of single-strand DNA breaks in operation theatre personnel. AB - Volatile anaesthetics such as halothane, isoflurane and others were expected to produce a health challenge for operation room personnel because of prolonged occupational exposure to anaesthetic gases. To estimate a molecular background of adverse health effects, a cohort of 100 exposed individuals was studied by the single-cell gene electrophoresis (comet assay) test. DNA lesions in lymphocytes of the exposed group did not differ significantly compared with non-exposed blood donors. Then, the exposed group was further divided according to job position. A highest level of DNA lesions was established in nurses but without significant difference compared with other groups. When a time period of exposure was taken into account, a tendency to cumulate DNA lesions was found only in the group of anaesthesiologists. A very weak genotoxic effect established in this study is discussed in relation to DNA repair, adaptative response and potential self elimination of sensitive individuals. PMID- 26685862 TI - Ineffective Esophageal Motility (IEM): the Old-New Frontier in Esophagology. AB - Ineffective esophageal motility (IEM) is characterized by distal esophageal contraction amplitude of <30 mmHg on conventional manometry (Blonski et al. Am J Gastroenterol. 103(3):699-704, 2008), or a distal contractile integral (DCI) < 450 mmHg*s*cm on high-resolution manometry (HRM) (Kahrilas et al. Neurogastroenterol Motil. 27(2):160-74, 2015) in>=50 % of test swallows. IEM is the most common abnormality on esophageal manometry, with an estimated prevalence of 20-30 % (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004; Conchillo et al. Am J Gastroenterol. 100(12):2624-32, 2005). Non-obstructive dysphagia has been considered to be frequently associated with severe esophageal peristaltic dysfunction. Defective bolus transit (DBT) on multichannel intraluminal impedance testing was found in more than half of IEM patients who presented with dysphagia (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004), highlighting the functional defect of this manometric finding. Treatment of IEM has been challenging because of lack of promotility agents that have a definite effect on esophageal function. PMID- 26685863 TI - Masked Translation Priming Effects in Visual Word Recognition by Trilinguals. AB - The present study aims to investigate how trilinguals process their two non dominant languages and how those languages influence one another, as well as the relative importance of the dominant language on their processing. With this in mind, 24 French (L1)- English (L2)- and Spanish (L3)-unbalanced trilinguals, deemed equivalent in their L2 and L3 were recruited. They were asked to perform two series of lexical decisions in the two non-native languages (L2 and L3), with a masked translation priming paradigm. Target words in both languages were primed by either the same word (repetition), a translation (in one of the other languages) or an unrelated word (in L1, L2 or L3). The results highlighted a strong link between prime and target, with an effect of repetition for both target languages. Moreover, a translation priming effect was demonstrated, only when the primes belongs to the dominant L1, i.e. L2 and L3 target words were identified faster when they were primed by the L1 translation. No translation priming effects were found for L2 and L3 primes. These results are in line with a multilingual lexicon organized by the L1, with a lack of cross-language interactions between the two non-dominant languages. PMID- 26685864 TI - ChIP bias as a function of cross-linking time. AB - The chromatin immunoprecipitation (ChIP) assay is widely used to capture interactions between chromatin and regulatory proteins in vivo. Formaldehyde cross-linking of DNA and proteins is a critical step required to trap their interactions inside the cells before immunoprecipitation and analysis. Yet insufficient attention has been given to variables that might give rise to artifacts in this procedure, such as the duration of cross-linking. We analyzed the dependence of the ChIP signal on the duration of formaldehyde cross-linking time for two proteins: DNA topoisomerase 1 (Top1) that is functionally associated with the double helix in vivo, especially with active chromatin, and green fluorescent protein (GFP) that has no known bona fide interactions with DNA. With short time of formaldehyde fixation, only Top1 immunoprecipation efficiently recovered DNA from active promoters, whereas prolonged fixation augmented non specific recovery of GFP dramatizing the need to optimize ChIP protocols to minimize the time of cross-linking, especially for abundant nuclear proteins. Thus, ChIP is a powerful approach to study the localization of protein on the genome when care is taken to manage potential artifacts. PMID- 26685865 TI - Preimplantation embryo-secreted factors modulate maternal gene expression in rat uterus. AB - In mammalian reproduction, embryo implantation into the uterus is spatiotemporally regulated by a complex process triggered by a number of factors. Although previous studies have suggested that uterine receptivity is mediated by blastocyst-derived factors, specific functions of embryos remain to be defined during preimplantation. Therefore, the present study was conducted to identify the maternal genes regulated by embryo-secreted factors in the rat uterus. RNA sequencing (RNA-seq) data revealed that 10 genes are up-regulated in the delayed implantation uterus compared with the pseudopregnancy uterus. The RNA-seq results were further verified by real-time quantitative polymerase chain reaction. Sulf1 expression is significantly (P < 0.05) induced in the delayed implantation uterus, although Areg, Calca, Fxyd4 and Lamc3 show a definite but non statistically significant increase in their expression levels. During early pregnancy, the levels of Areg, Calca, Fxyd4, Lamc3 and Sulf1 expression at 3.5 days post coitus (dpc) are significantly (P < 0.05) higher than those at 1.5 dpc. Treatment with embryo-conditioned media revealed that Lamc3 and Sulf1 are up regulated compared with the other genes studied. Thus, embryo-derived factors regulate maternal gene expression, with Lamc3 and Sulf1 possibly being suitable markers for a response study of embryo-secreted factors to improve our understanding of embryo-maternal communication. PMID- 26685866 TI - Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-related infertility. AB - Endometriosis, a highly prevalent gynecological disease, is often associated with infertility, even in its milder forms (minimal and mild endometriosis). However, no consensus has been established with regard to this relationship and the possible mechanisms involved have not been completely elucidated. The oocyte is believed to have an important role in the infertility presented by these patients. Hence, oxidative stress events associated with alterations in the peritoneal, serum and/or follicular microenvironments might result in poor oocyte quality and compromise the reproductive potential of these women. Here, we review possible mechanisms involved in oocyte quality impairment that might lead to infertility in patients with early endometriosis. PMID- 26685867 TI - Altered Neural Correlate of the Self-Agency Experience in First-Episode Schizophrenia-Spectrum Patients: An fMRI Study. AB - BACKGROUND: The phenomenology of the clinical symptoms indicates that disturbance of the sense of self be a core marker of schizophrenia. AIMS: To compare neural activity related to the self/other-agency judgment in patients with first-episode schizophrenia-spectrum disorders (FES, n = 35) and healthy controls (HC, n = 35). METHOD: A functional magnetic resonance imaging (fMRI) using motor task with temporal distortion of the visual feedback was employed. A task-related functional connectivity was analyzed with the use of independent component analysis (ICA). RESULTS: (1) During self-agency experience, FES showed a deficit in cortical activation in medial frontal gyrus (BA 10) and posterior cingulate gyrus, (BA 31; P < .05, Family-Wise Error [FWE] corrected). (2) Pooled-sample task-related ICA revealed that the self/other-agency judgment was dependent upon anti-correlated default mode and central-executive networks (DMN/CEN) dynamic switching. This antagonistic mechanism was substantially impaired in FES during the task. DISCUSSION: During self-agency experience, FES demonstrate deficit in engagement of cortical midline structures along with substantial attenuation of anti-correlated DMN/CEN activity underlying normal self/other-agency discriminative processes. PMID- 26685868 TI - Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging. AB - Alternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome-wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild-type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3-3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson-Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild-type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known. PMID- 26685869 TI - Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: A pooled secondary analysis of clinical trials. AB - Use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) has been reported to be associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with vascular endothelial growth factor-targeted therapies. This study was a secondary pooled analysis of two Phase III randomized controlled trials (RCTs) of patients with mRCC: NCT00334282 comparing pazopanib to placebo and NCT00720941 comparing pazopanib to sunitinib. ASI users were defined as patients using an ASI at baseline. Association with overall survival (OS; primary outcome) and progression-free survival (PFS) was evaluated using Cox proportional hazards regression. The association was adjusted in multivariable analysis for baseline systolic blood pressure (SBP), use of other antihypertensive drugs and prognostic factors comprising the Heng risk criteria for mRCC. Of 1,545 patients pooled from the two RCTs, 649 (42%) were using one or more antihypertensive drugs at baseline, 385 (59%) of which were using an ASI. In the multivariable analysis of patients using pazopanib or sunitinib, no significant association was observed between baseline ASI use and OS (hazard ratio [HR] 0.97 [95% confidence interval (CI) 0.80-1.18], p = 0.80) or PFS (HR 0.88 [95% CI 0.73-1.06], p = 0.17). Exploratory subgroup analysis of NCT00720941 highlighted that the effect of baseline ASI use on OS may differ between patients treated with sunitinib and pazopanib. In conclusion, use of ASIs at baseline was not a significant independent prognostic factor for improved survival in a pooled analysis of mRCC patients treated with pazopanib or sunitinib. PMID- 26685870 TI - Psychosocial oncology care resources in Europe: a study under the European Partnership for Action Against Cancer (EPAAC). AB - BACKGROUND: Cancer is a complex health problem requiring multidisciplinary care. There are clinical guidelines available in order to improve the process and outcomes of cancer care within Europe. However, strategic action is still needed in many European Union (EU) Member States to develop or improve national cancer control plans (NCCPs), which play a key role in cancer control and care. The current study clarifies the extent of implementation of psychosocial oncology care (PSOC) in the EU. METHOD: A survey methodology was used to cover four dimensions: (1) inclusion of PSOC in NCCPs; (2) structure and resources of PSOC delivery; (3) use of NCCP clinical guidelines; and (4) education and training resources available along with determination of training needs in PSOC. RESULTS: Twenty-seven (90%) countries returned questionnaires of which 21 (78%) include PSOC in their NCCP. However, only 10 (37%) reported having specific budgets for PSOC, 8 (30%) having nationally recommended PSOC clinical guidelines, and 6 countries (22%) reported having an official certification for PSOC education. CONCLUSION: Although many countries seem to have integrated PSOC into their NCCP, there is still much to do in terms of allocating resources and delivering psychosocial care equitably. Also, there is a need for improving training and certification in PSOC. The findings indicate the need to develop national policies concerning PSOC with clear targets for deliverables in an appropriate timetable in order that psychosocial services and existing clinical guidelines are implemented and fully integrated into EU NCCPs. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26685871 TI - Dental implants in patients with oral mucosal diseases - a systematic review. AB - To reveal dental implants survival rates in patients with oral mucosal diseases: oral lichen planus (OLP), Sjogren's syndrome (SjS), epidermolysis bullosa (EB) and systemic sclerosis (SSc). A systematic literature search using PubMed/Medline and Embase databases, utilising MeSH and search term combinations identified publications on clinical use implant-prosthetic rehabilitation in patients with OLP, SjS, EB, SSc reporting on study design, number, gender and age of patients, follow-up period exceeding 12 months, implant survival rate, published in English between 1980 and May 2015. After a mean observation period (mOP) of 53.9 months (standard deviation [SD] +/-18.3), 191 implants in 57 patients with OLP showed a survival rate (SR) of 95.3% (SD +/-21.2). For 17 patients with SjS (121 implants, mOP 48.6 +/- 28.7 months), 28 patients with EB (165 implants, mOP 38.3 +/- 16.9 months) and five patients with SSc (38 implants, mOP 38.3 +/- 16.9 months), the respective SR was 91.7 +/- 5.97% (SjS), 98.5 +/- 2.7% (EB) and 97.4 +/- 4.8% (SSc). Heterogeneity of data structure and quality of reporting outcomes did not allow for further comparative data analysis. For implant-prosthetic rehabilitation of patients suffering from OLP, SjS, EB and SSc, no evidence-based treatment guidelines are presently available. However, no strict contraindication for the placement of implants seems to be justified in patients with OLP, SjS, EB nor SSc. Implant survival rates are comparable to those of patients without oral mucosal diseases. Treatment guidelines as for dental implantation in patients with healthy oral mucosa should be followed. PMID- 26685872 TI - Field evaluation of baited traps for surveillance of Aedes japonicus japonicus in Switzerland. AB - The efficacy of Centers for Disease Control (CDC) miniature light traps and ovitraps was tested in the outskirts of the city of Zurich in Switzerland for their use in the surveillance of Aedes (Hulecoeteomyia) japonicus japonicus (Theobald) (Diptera: Culicidae), the invasive Asian bush mosquito. Sets of single CDC traps were run overnight (n = 18) in three different environments (forest, suburban and urban) in 3 * 3 Latin square experimental designs. Traps were baited with: (a) carbon dioxide (CO2 ); (b) CO2 plus light, or (c) CO2 plus lure blend [Combi FRC 3003 (iGu(r) )]. At the same locations, mosquito eggs were collected weekly using standard ovitraps baited with different infusions (oak, hay or tap water) and equipped with different oviposition substrates (a block of extruded polystyrene, a germination paper strip or a wooden stick). Data were analysed using Poisson and negative binomial general linear models. The use of light (P < 0.001) or lure (P < 0.001) significantly increased the attractiveness of CDC traps baited with CO2 . Oak and hay infusions did not increase the attractiveness of ovitraps compared with standing tap water (P > 0.05), and extruded polystyrene blocks were preferred as an oviposition substrate over wooden sticks (P < 0.05) and seed germination paper (P < 0.05). Carbon dioxide-baited CDC miniature light traps complemented with light or iGu(r) lure and ovitraps containing standing tap water and polystyrene oviposition blocks can be considered as efficient and simple tools for use in Ae. j. japonicus surveillance programmes. PMID- 26685873 TI - Role of dopamine in motor cortex plasticity in Parkinson's disease. PMID- 26685874 TI - Effects of gum chewing exercises on saliva secretion and occlusal force in community-dwelling elderly individuals: A pilot study. AB - AIM: Elderly individuals face the risk of reductions in saliva secretion and occlusal force caused by systemic diseases or medications that can eventually result in malnutrition and systemic complications. We tested the hypothesis that regular gum chewing exercises (GCE) would enhance saliva secretion and occlusal force in an elderly population. METHODS: A total of 12 community-dwelling elderly individuals (3 men and 9 women) participated in this study after providing informed consent. Participants carried out GCE regimens using a soft gum (GCE-S) or hard gum (GCE-H) for 2 weeks each, with a 2-week rest period between trials. Mucosal moisture on the tongue surface, resting saliva, and occlusal force were measured before and after each test gum, and changes in parameters at relevant time-points were statistically analyzed. Differences in each measurement item were assessed using the Friedman test for before and after the GCE. We used the Holm's correction for multiple comparisons if the Friedman test results were significant. The critical value for rejecting the null hypothesis was set at P < 0.05. RESULTS: Resting saliva secretion significantly increased after GCE-S, returned to baseline levels during the rest period and significantly increased again after GCE-H. Mucosal moisture and occlusal force followed a similar trend, with a significant rise after GCE-H. CONCLUSIONS: The results of the present study suggest that GCE can increase resting saliva secretion and occlusal force in elderly individuals. Further investigations are required on the appropriate use of soft and hard gums to address oral frailty in elderly individuals. Geriatr Gerontol Int 2017; 17: 48-53. PMID- 26685875 TI - A neurophysiologic view on mental disorder. PMID- 26685877 TI - Utility of flexion-extension radiography for the detection of ligamentous cervical spine injury and its current role in the clearance of the cervical spine. AB - Detecting the presence of injuries to the cervical spine is an important component of the initial assessment of patients sustaining blunt trauma. A small proportion of cervical spine injuries consists of ligamentous disruption. Accurate detection of ligamentous injury is essential as it may result in sequelae including radiculopathy, quadriplegia and death. Flexion-extension (FE) radiography has traditionally been utilised for the detection of ligamentous injury in patients who have been cleared of bony injury. There are controversies surrounding the use of FE for alert patients with neck pain. There are studies that call into question the diagnostic accuracy of FE, the high proportion of inadequate FE images due to muscle spasm and the adverse effects of prolonged cervical collar immobilisation while awaiting FE. Other literature indicates that FE provides no additional diagnostic information following a multi-detector helical computed tomography. This review evaluates the literature on the utility of FE for the detection of ligamentous injury and explores alternate strategies for clearing the cervical spine of ligamentous injury. PMID- 26685876 TI - The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies. AB - BACKGROUND: Congenital enteric neuropathies of the distal intestine (CEN) are characterized by the partial or complete absence of enteric neurons. Over the last decade, zebrafish has emerged as a leading model organism in experimental research. Our aim was to demonstrate that the mutant zebrafish, lessen, expressing CEN characteristics, is an equally valuable animal model alongside mammalian models for CEN, by studying its enteric phenotype. METHODS: The effect of the lessen mutation on the development of the enteric nervous system (ENS), interstitial cells of Cajal (ICC), and intestinal motility in each intestinal region of mutant and wild-type (wt) zebrafish embryos at 3-6 dpf, was analyzed by immunofluorescent detection of neurochemical markers and motility assays. KEY RESULTS: Development of intestinal motility in the mutant was delayed and the majority of the observed contractions were disturbed. A significant disturbance in ENS development resulted in a distal intestine that was almost free of neuronal elements, in reduced neuronal density in the proximal and mid-intestine, and in a defect in the expression of neurochemical markers. Furthermore, markedly disturbed development of ICC gave rise to a less dense network of ICC. CONCLUSIONS & INFERENCES: The observed alterations in intestinal motility, intrinsic innervation and ICC network of the mutant in comparison with the wt zebrafish, are similar to those seen in the oligo- and aganglionic regions of the intestine of CEN patients. It is concluded that the zebrafish mutant lessen is an appropriate animal model to investigate CEN. PMID- 26685878 TI - Parathyroid carcinoma with contralateral subcutaneous and breast recurrences: A rare presentation. AB - BACKGROUND: Parathyroid carcinoma is extremely rare. Correct preoperative and even histopathological diagnosis may be difficult owing to the deceptively bland cytoarchitectural features, especially when presenting with localized disease. Recurrence/metastases developing years later then make the malignant nature obvious. METHODS AND RESULTS: We present here an unusual case of a 32-year-old patient with carcinoma of the left upper parathyroid gland, initially diagnosed as parathyroid adenoma, treated with endoscopic left parathyroidectomy, and later developing subcutaneous metastatic nodules over the medial end of the right clavicle and right anterior chest wall, followed by a right breast deposit. The recurrences, especially subcutaneous ones, were probably secondary to tumor seeding along the track of insertion of the endoscope. CONCLUSION: Involvement of subcutaneous tissue and the breast in parathyroid carcinoma is extremely rare. The case is being reported for its uniqueness along with a discussion of possible appropriate course of management, which may have averted the aggressive clinical course of the disease. PMID- 26685879 TI - Space-discretization error analysis and stabilization schemes for conduction velocity in cardiac electrophysiology. AB - In cardiac electrophysiology, the propagation of the action potential may be described by a set of reaction-diffusion equations known as the bidomain model. The shape of the solution is determined by a balance of a strong reaction and a relatively weak diffusion, which leads to steep variations in space and time. From a numerical point of view, the sharp spatial gradients may be seen as particularly problematic, because computational grid resolution on the order of 0.1 mm or less is required, yielding considerable computational efforts on human geometries. In this paper, we discuss a number of well-known numerical schemes for the bidomain equation and show how the quality of the solution is affected by the spatial discretization. In particular, we study in detail the effect of discretization on the conduction velocity (CV), which is an important quantity from a physiological point of view. We show that commonly applied finite element techniques tend to overestimate the CV on coarse grids, while it tends to be underestimated by finite difference schemes. Furthermore, the choice of interpolation and discretization scheme for the nonlinear reaction term has a strong impact on the CV. Finally, we exploit the results of the error analysis to propose improved numerical methods, including a stabilized scheme that tends to correct the CV on coarse grids but converges to the correct solution as the grid is refined. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26685880 TI - Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds. AB - Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inhibitor to the C-terminal domain of HIV-1 CA (capsid). Screening of >70000 compounds from different libraries identified 2-arylquinazolines as low micromolecular inhibitors of HIV-1 capsid assembly. We prepared focused libraries of modified 2-arylquinazolines and tested their capacity to bind HIV-1 CA to compete with the known peptide inhibitor and to prevent the replication of HIV-1 in tissue culture. Some of the compounds showed potent binding to the C-terminal domain of CA and were found to block viral replication at low micromolar concentrations. PMID- 26685881 TI - High-frequency video capture and a computer program with frame-by-frame angle determination functionality as tools that support judging in artistic gymnastics. AB - PURPOSE: The main aim of this study was to verify the usefulness of selected simple methods of recording and fast biomechanical analysis performed by judges of artistic gymnastics in assessing a gymnast's movement technique. MATERIAL AND METHODS: The study participants comprised six artistic gymnastics judges, who assessed back handsprings using two methods: a real-time observation method and a frame-by-frame video analysis method. They also determined flexion angles of knee and hip joints using the computer program. RESULTS: In the case of the real-time observation method, the judges gave a total of 5.8 error points with an arithmetic mean of 0.16 points for the flexion of the knee joints. In the high speed video analysis method, the total amounted to 8.6 error points and the mean value amounted to 0.24 error points. For the excessive flexion of hip joints, the sum of the error values was 2.2 error points and the arithmetic mean was 0.06 error points during real-time observation. The sum obtained using frame-by-frame analysis method equaled 10.8 and the mean equaled 0.30 error points. CONCLUSIONS: Error values obtained through the frame-by-frame video analysis of movement technique were higher than those obtained through the real-time observation method. The judges were able to indicate the number of the frame in which the maximal joint flexion occurred with good accuracy. Using the real-time observation method as well as the high-speed video analysis performed without determining the exact angle for assessing movement technique were found to be insufficient tools for improving the quality of judging. PMID- 26685882 TI - Spontaneous oral chytridiomycosis in wild bullfrog tadpoles in Japan. AB - Batrachochytrium dendrobatidis (Bd) infects Anuran larvae (tadpole) mouthparts and causes oral chytridiomycosis, which can be diagnosed in tadpoles by detecting mouthparts deformities. However, oral chytridiomycosis may or may not be observable, depending on species, tadpole stage and season, and has never been reported in Japan. We aimed to observe oral chytridiomycosis characteristics in bullfrog (Lithobates catesbeiana) tadpoles, determine associated pathologic features and investigate the usability of bullfrog tadpoles in Japanese Bd field surveys. Wild-captured bullfrog tadpole mouthparts were examined macroscopically, histopathologically and by molecular biological examination. Macroscopic lesions were observed in 21 of 59 tadpole mouthparts. Lesions were most frequently located in the lower jaw sheaths and were mainly recognized by partial depigmentation (11 tadpoles; some were completely depigmented) and thinning of the pigmented layer (10 tadpoles). Partial defects of the tips and blunt cutting edges of the jaw sheaths were observed with severe jaw sheath depigmentation. Whitened tooth rows were observed in 7 tadpoles. Histologically, the stratified epithelium (pigmented epithelium) showed partial or diffuse hypopigmentation or pigment loss. Irregular stratified epithelium thickening with hyperkeratosis or parakeratosis was observed in the jaw sheaths. Bd infection was confirmed in 20 of 21 tadpoles presenting jaw sheath deformities, by histopathological examination and/or nested polymerase chain reaction. Depigmentation and thinning of the pigmented layers of jaw sheaths were associated with Bd infection. Thus, diagnosis of Bd infection by macroscopic observation of bullfrog tadpole mouthparts is feasible. This is the first report of oral chytridiomycosis in wild bullfrog tadpoles in Japan. PMID- 26685883 TI - The pathogenic potential of Helicobacter cinaedi isolated from non-human sources: adherence, invasion and translocation ability in polarized intestinal epithelial Caco-2 cells in vitro. AB - Helicobacter cinaedi infection has been recognized as an increasingly important emerging disease in humans. Infection with H. cinaedi causes bacteremia, cellulitis and enteritis. H. cinaedi has been isolated from non-human sources, including dogs, cats and rodents; however, it remains unclear whether animal strains are pathogenic in humans and as zoonotic pathogens. In this study, H. cinaedi isolates were recovered from a dog and a hamster, and the ability of these isolates to adhere to, invade and translocate across polarized human intestinal epithelial Caco-2 cells was examined in vitro. To better understand the pathogenic potential of animal H. cinaedi isolates, these results were compared with those for a human strain that was isolated from a patient with bacteremia. The animal and human strains adhered to and invaded Caco-2 cells, but to a lesser degree than the C. jejuni 81-176 strain, which was used as a control. The integrity of tight junctions was monitored by measuring transepithelial electrical resistance (TER) with a membrane insert system. The TER values for all H. cinaedi strains did not change during the experimental periods compared with those of the controls; however, translocation of H. cinaedi from the apical side to the basolateral side was confirmed by cultivation and H. cinaedi-specific PCR, suggesting that the H. cinaedi strains translocated by transcellular route. This study demonstrated that H. cinaedi strains of animal origin might have a pathogenic potential in human epithelial cells as observed in a translocation assay in vitro with a human isolate. PMID- 26685885 TI - Ternary polybenzoxazine/POSS/SWCNT hybrid nanocomposites stabilized through supramolecular interactions. AB - In this study we linked zero-dimensional polyhedral oligomeric silsesquioxane (POSS) with one-dimensional single-walled carbon nanotubes (SWCNTs) as dual dimensional nanohybrid complexes within polybenzoxazine matrices, stabilized through noncovalent supramolecular interactions. First, we synthesized a new bifunctionalized benzoxazine (Py-Bz-T), presenting thymine (T) and pyrene (Py) units, that displayed excellent thermal properties after thermal curing, because its T moieties increased the physical cross-linking density. Second, we prepared Py-Bz-T/OBA-POSS [octuply adenine (A)-functionalized POSS] nanocomposites and investigated, using nuclear magnetic resonance and Fourier transform infrared spectroscopies, the multiple hydrogen bonding AT interactions between Py-Bz-T and OBA-POSS. Finally, we prepared Py-Bz-T/OBA-POSS/SWCNT ternary hybrid complexes dispersed in THF, stabilized through both multiple hydrogen bonding and pi-pi stacking interactions. Transmission electron microscopy revealed that the SWCNTs were highly dispersed and covered by the Py-Bz-T/OBA-POSS nanocomposites; these ternary hybrid complexes were stabilized through pi-pi interactions between Py-Bz T/OBA-POSS and the SWCNTs, as evidenced using fluorescence spectroscopy. PMID- 26685884 TI - Ventricular assist devices and non-cardiac surgery. AB - The use of ventricular assist devices has expanded significantly since their approval by the Food and Drug Administration in the United States in 1994. In addition to this, the prevalence of heart failure continues to increase. We aim to provide an overview of perioperative considerations and management of these patients for non-cardiac surgery. We performed a Medline search for the words "ventricular assist device," "Heartmate" and "HeartWare" to gain an overview of the literature surrounding these devices, and chose studies with relevance to the stated aims of this review. Patients with ventricular assist devices are presenting more frequently for surgery not related to their cardiac pathology. As the mechanically supported population grows, general anesthesiologists will be faced with managing these patients, possibly outside of the tertiary care setting. The unique challenges of this patient population can best be addressed by a thorough understanding of ventricular assist device physiology and a multidisciplinary approach to care. PMID- 26685886 TI - Sialylation: an Avenue to Target Cancer Cells. AB - Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration. PMID- 26685887 TI - The treatment of anterior vaginal wall prolapsed by repair with mesh versus colporrhaphy. AB - PURPOSE: To compare patient outcomes of mesh repair and colporrhaphy for the treatment of anterior vaginal wall prolapse (AVP). MATERIALS AND METHODS: We searched PubMed((r)), Embase((r)), and Cochrane Library databases to identify the included studies. The outcome measures included anatomical success, patient satisfaction, patient sexual function, perioperative data, and complications. Statistical analyses were performed using Cochrane Collaboration Review Manager software (RevMan 5.1.4). RESULTS: The study inclusion criteria were met by 11 articles involving 1455 patients. Synthesized data indicated that mesh surgery was more complex than colporrhaphy with regard to perioperative condition [mean difference (MD) 0.28, 95% confidence interval (CI) 0.07-0.49, p = 0.010]. There were no significant differences for the following complications: urinary retention [relative risk (RR) 1.12, 95% CI 0.65-1.94, p = 0.68], urinary incontinence (RR 1.01, 95% CI 0.63-1.63, p = 0.96), voiding difficulty (RR 1.11, 95% CI 0.69-1.80, p = 0.66), dyspareunia (RR 1.21, 95% CI 0.87-1.67, p = 0.26), urinary tract infection (RR 1.15, 95% CI 0.74-1.78, p = 0.53), and vaginal bulge (RR 1.08, 95% CI 0.93-1.25, p = 0.32). There were instances of more serious complications in group 1, i.e., the mesh group. However, AVP cure rate was significantly higher in the mesh group (RR 1.44, 95% CI 1.34-1.55, p < 0.00001). The cure rate was not significantly dependent on patient satisfaction (RR 1.10, 95% CI 0.96-1.26, p = 0.16) or postoperative sexual function (RR 1.03, 95% CI 0.90-1.11, p = 0.71). CONCLUSIONS: Surgical repair with the mesh procedure appears to be a better choice for the treatment of anterior vaginal wall prolapse. PMID- 26685888 TI - Which play a more important role in the development of large-sized prostates (>=80 ml), androgen receptors or oestrogen receptors? A comparative study. AB - OBJECTIVE: To compare the expression levels of androgen receptor (AR), oestrogen receptor alpha (ERalpha)and oestrogen receptor beta (ERbeta) in human prostate with various degrees of benign hyperplasia. MATERIALS AND METHODS: Forty-five BPH patients undergoing transurethral plasmakinetic resection of the prostate were divided into three 15-people groups of participants with small (<40 ml), medium (40-80 ml) and large (>80 ml) prostates. Patient blood samples were collected for measuring serum oestradiol (E2), total testosterone (TT), follicle-stimulating and luteinizing hormone by radioimmunoassay. Postoperative prostate specimens were collected to detect AR, ERalpha and ERbeta expression by immunoblotting and immunohistochemical staining. RESULTS: There were significantly lower serum E2 levels in the patients with large prostates compared to the patients with small prostates (P < 0.05) and medium prostates (P < 0.01). A high TT and E2 serum ratio was observed in patients with large-sized prostates (P < 0.05), but there were no obvious differences in the serum TT levels between the three groups. Prostate AR expression in patients with large- (P < 0.05) and medium-sized prostates (P < 0.01) was high compared to patients with small-sized prostates. Prostate ERalpha expression in patients with large prostates was low compared to patients with small- and medium-sized prostates (P < 0.01). The prostate ERbeta expression did not differ between the three groups (P > 0.05). CONCLUSIONS: Increased AR and decreased ERalpha expression in the prostate suggested that AR might be more important than ERalpha in stimulating prostate proliferation in patients with large-sized prostates. Patients with small- and large-sized prostates might require different management procedures involving selective oestrogen receptor modulators and selective androgen receptor modulators, respectively. PMID- 26685890 TI - Structures and unimolecular chemistry of M(Pro2-H)(+) (M = Mg, Ca, Sr, Ba, Mn, Fe, Co, Ni, Cu, Zn) by IRMPD spectroscopy, SORI-CID, and theoretical studies. AB - M(Pro2-H)(+) complexes were electrosprayed and isolated in an FTICR cell where their unimolecular chemistries and structures were explored using SORI-CID and IRMPD spectroscopy. These experiments were augmented by computational methods such as electronic structure, simulated annealing, and atoms in molecules (AIM) calculations. The unimolecular chemistries of the larger metal cation (Ca(2+), Sr(2+) and Ba(2+)) complexes predominantly involve loss of neutral proline whereas the complexes involving the smaller Mg(2+) and transition metal dications tend to lose small neutral molecules such as water and carbon dioxide. Interestingly, all complexes involving transition metal dications except for Cu(Pro2-H)(+) lose H2 upon collisional or IRMPD activation. IRMPD spectroscopy shows that the intact proline in the transition metal complexes and Cu(Pro2-H)(+) is predominantly canonical (charge solvated) while for the Ca(2+), Sr(2+), and Ba(2+) complexes, proline is in its zwitterionic form. The IRMPD spectra for both Mg(Pro2-H)(+) and Mn(Pro2-H)(+) are concluded to have contributions from both charge-solvated and canonical structures. PMID- 26685889 TI - Clinical characteristics and long-term observation of simple renal cysts in a healthy Korean population. AB - PURPOSE: Although simple renal cysts are common in older patients, little is known concerning their development and natural history. We investigated the characteristics of simple renal cysts and risk factors for their development in healthy Korean adults. MATERIALS AND METHODS: The medical records of 10,261 subjects who participated in a multiphase health screening program at our institution in 2002 were reviewed. Logistic regression analysis was used to examine various risk factors for renal cyst formation including sex, age, BMI, serum creatinine, estimated GFR, proteinuria, microscopic hematuria, hypertension, hypercholesterolemia, and diabetes mellitus. In 65 patients and 79 simple renal cysts with annual follow-up for 10 years, sequential changes in size and risk factors related to cyst growth rate were analyzed. RESULTS: The prevalence of simple renal cysts was 5.43 %. Age (p < 0.001), BMI (p < 0.001), proteinuria (p = 0.011), microscopic hematuria (p < 0.001), estimated GFR (p < 0.001), and hypertension (p < 0.001) had a significant influence on the occurrence of simple renal cysts. The average growth rates of simple renal cysts over the 10-year follow-up period were 1.43 mm (6.5 %) per year. Age <50 years was the only significant predictor of growth rates of renal cysts in the multivariate analysis (beta = 2.37; 95 % CI 0.52, 4.22; p = 0.013). CONCLUSION: Age, BMI, renal dysfunction, proteinuria, microscopic hematuria, and hypertension were found to be risk factors for the presence of simple renal cysts. Simple renal cysts in younger patients (<50 years) tend to have a more rapid increase in size, but generally do not progress to aggressive disease. PMID- 26685891 TI - Room temperature methoxylation in zeolites: insight into a key step of the methanol-to-hydrocarbons process. AB - Neutron scattering methods observed complete room temperature conversion of methanol to framework methoxy in a commercial sample of methanol-to-hydrocarbons (MTH) catalyst H-ZSM-5, evidenced by methanol immobility and vibrational spectra matched by ab initio calculations. No methoxylation was observed in a commercial HY sample, attributed to the dealumination involved in high silica HY synthesis. PMID- 26685892 TI - The role of elective superficial parotidectomy in the treatment of temporal region squamous cell carcinoma. AB - OBJECTIVE: In order to determine rates of metastasis and efficacy of elective superficial parotidectomy, we examine parotid specimens in patients with temporal region cutaneous squamous cell carcinoma treated with local excision and ipsilateral parotidectomy. STUDY DESIGN: This paper is a retrospective review. SETTING: This study was conducted at a private tertiary referral practice in Fort Worth, Texas, from 1998 to 2013. SUBJECTS AND METHODS: Ninety-three patients between ages 27 and 98 with primary squamous cell carcinoma of the temporal region greater than or equal to 2 cm were included in this study. Subjects had no evidence of adenopathy or parotid involvement on exam or imaging. Patients were treated with local excision and ipsilateral parotidectomy. The primary tumor was studied for vascular involvement and perineural invasion while the parotid specimen was analyzed for occult cancer. Patients were post-operatively followed for a minimum of three years. RESULTS: Twenty-three (24.7 %) parotid samples were found to harbor occult malignancy. Of these, nine (39.1 %) patients had vascular involvement of the primary tumor and 14 (60.8 %) had perineural invasion. Thirteen out of 58 affected males and 10 out of 35 affected females were found to have intraparotid node positivity. Vascular involvement (p = 0.0004) and perineural invasion (p = 0.0001) in the primary malignancy were found to be greater in patients with positive specimen. Sex was not statistically significant. CONCLUSIONS: In patients with cutaneous squamous cell carcinoma of the temporal region at least 2 cm in size, elective superficial parotidectomy may be a beneficial part of treatment, especially in primary tumors showing perineural and/or vascular involvement. LEVEL OF EVIDENCE: Level 2b (retrospective cohort). PMID- 26685893 TI - Shape-controlled synthesis of Cu31S16-metal sulfide heteronanostructures via a two-phase approach. AB - A series of different-shaped Cu31S16-metal sulfide (ZnS, CdS and CuInS2) heteronanostructures have been synthesized using a simple two-phase approach for the first time. This two-phase approach may shed light on the synthesis of Cu31S16-based heteronanostructures. PMID- 26685894 TI - Discovery of a ternary pseudobrookite phase in the earth-abundant Ti-Zn-O system. AB - We combine theory with experiment in searching for "missing", stable materials within the Zn-Ti-O chemical system, leading to the discovery of a new pseudobrookite phase, ZnxTi3-xO5-delta. This ternary system was chosen for (1) technological relevance, (2) earth abundance, and (3) the fact that many compounds in this system are predicted from enthalpies of formation to be borderline stable, suggesting an important role of entropic contributions in their stabilization and making this chemical system a perfect test bed for exploring the limits of theoretical predictions. The initial set of exploratory experimental syntheses, via sintering in evacuated ampoules and quenching, resulted in a single phase ZnxTi3-xO5-delta composition with x ~ 0.6 and an almost stoichiometric oxygen content, as evaluated by X-ray fluorescence, energy dispersive spectroscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The theoretically calculated lowest energy crystal structure for the closest stoichiometric ZnTi5O10 composition matched that measured experimentally by synchrotron X-ray diffraction (allowing for differences attributable to cation disorder). The measured broad optical absorption, n-type electrical conductivity, and stability in acidic media are comparable to those of other ternary pseudobrookites and Ti-O Magneli phases, suggesting comparable applicability as a robust electrode or catalyst support in electrochemical devices or water remediation. However, the new phase decomposes upon heating in air as it oxidizes. The success of the present approach to identify a "missing material" in an earth-abundant and applications-rich system suggests that future efforts to experimentally realize and theoretically confirm missing materials in this and similar systems are warranted, both scientifically and technologically. PMID- 26685895 TI - Protonated thiophene-based oligomers as formed within zeolites: understanding their electron delocalization and aromaticity. AB - In an earlier work, protonated thiophene-based oligomers were identified inside ZSM-5 zeolites. The novel compounds exhibited pi-pi* absorption wavelengths deep within the visible region, earmarking them for possible use as chromophores in a variety of applications. In this computational study, we determine the factors that cause such low-energy transitions, and describe the electronic structure of these remarkable compounds. DFT calculations of conjugated thiophene-based oligomers with up to five monomer units reveal that the main absorption band of each protonated oligomer is strongly red-shifted compared to the unprotonated form. This effect is counterintuitive, since protonation is expected to diminish aromaticity, and thereby increase the HOMO-LUMO gap. We find that upon protonation the pi-electrons remain delocalized over the entire pi-conjugated molecule, but the positive charge is localized predominantly on the protonated side of the molecule. A possible explanation for this ground-state charge localization is the participation of the C-H bond in the pi-system of the protonated ring, locally providing aromatic stabilization for the positive charge. The addition of the proton stabilizes all electronic orbitals, but due to the ground state pi-electron distribution away from the added nucleus, the HOMO is stabilized less than the LUMO. The main absorption peak upon protonation corresponds to the charge transfer excitation involving the frontier orbitals, and the small band gap explains the observed red shift. Analogue calculations on thiophene within a ZSM-5 zeolite cluster model confirm the same trends upon protonation as observed in the non-interacting compounds. Understanding the electronic structure of these compounds is very relevant to correlate UV-Vis bands with acidic strength and possibly environment in zeolites and to improve their performance in catalytic and energy related applications. PMID- 26685896 TI - Central GABAA receptors are involved in inflammatory and cardiovascular consequences of endotoxemia in conscious rats. AB - gamma-Aminobutyric acid (GABA), the principal brain inhibitory neurotransmitter, modulates inflammatory and neurodegenerative disease. Here, we tested the hypothesis that central GABAergic neurotransmission mediates the detrimental inflammatory, hemodynamic, and cardiac autonomic actions of endotoxemia. The effects of drugs that block GABA receptors or interfere with GABA uptake or degradation on blood pressure (BP), heart rate (HR), and HR variability (HRV) responses elicited by i.v. lipopolysaccharide (LPS) were assessed in conscious rats. The hypotensive effect of LPS (10 mg/kg) was blunted after intracisternal (i.c.) administration of bicuculline (GABAA receptor antagonist) or saclofen (GABAB receptor antagonist). By contrast, the concomitant LPS-evoked tachycardia and decreases in time domain and frequency domain indices of HRV (measures of cardiac autonomic control) were abolished upon treatment with bicuculline but not saclofen. Increases in serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) caused by LPS disappeared in the presence of bicuculline or saclofen, whereas LPS-evoked increases in serum nitric oxide metabolites (NOx) were counteracted by bicuculline only. None of the endotoxemia effects was altered in rats treated with i.c. tiagabine (GABA reuptake inhibitor) or vigabatrin (GABA transaminase inhibitor). These data suggest a major role for central GABAA receptors in the inflammatory and cardiovascular effects of endotoxemia. PMID- 26685897 TI - Decreased Bronchial Eosinophilic Inflammation and Mucus Hypersecretion in Asthmatic Mice Lacking All Nitric Oxide Synthase Isoforms. AB - BACKGROUND: Asthma is characterized by airflow limitation with chronic airway inflammation, hyperresponsiveness and mucus hypersecretion. NO is generated by three nitric oxide synthase (i/n/eNOSs) isoforms, but conflicting results have been reported using asthmatic mice treated with NOSs inhibitors and NOS-knockout mice. To elucidate the authentic role of NO/NOSs in asthma, we used asthmatic mice lacking all NOSs (n/i/eNOS(-/-)). METHODS: Wild-type and n/i/eNOS(-/-) mice were sensitized and challenged with ovalbumin. Pathological findings and expressions of interferon (IFN)-gamma, interleukin (IL)-4, -5, -10, -13 and chemokines in the lung were evaluated. RESULTS: Decreased eosinophilic inflammation, bronchial thickening and mucus secretion, IL-4, -5 and -13, monocyte chemoattractant protein-1, eotaxin-1 and thymus and activation-regulated chemokine expressions were observed in n/i/eNOS(-/-) mice compared to wild-type, but expressions of IFN-gamma and IL-10 were similar. CONCLUSION: Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma. PMID- 26685898 TI - High-resolution morphologic and ultrashort time-to-echo quantitative magnetic resonance imaging of the temporomandibular joint. AB - OBJECTIVE: To implement high-resolution morphologic and quantitative magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) using ultrashort time-to-echo (UTE) techniques in cadavers and volunteers. METHODS: This study was approved by the institutional review board. TMJs of cadavers and volunteers were imaged on a 3-T MR system. High-resolution morphologic and quantitative sequences using conventional and UTE techniques were performed in cadaveric TMJs. Morphologic and UTE quantitative sequences were performed in asymptomatic and symptomatic volunteers. RESULTS: Morphologic evaluation demonstrated the TMJ structures in open- and closed-mouth position. UTE techniques facilitated the visualization of the disc and fibrocartilage. Quantitative UTE MRI was successfully performed ex vivo and in vivo, reflecting the degree of degeneration. There was a difference in the mean UTE T2* values between asymptomatic and symptomatic volunteers. CONCLUSIONS: MRI evaluation of the TMJ using UTE techniques allows characterization of the internal structure and quantification of the MR properties of the disc. Quantitative UTE MRI can be performed in vivo with short scan times. PMID- 26685899 TI - alpha-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways. AB - Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability, and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied alpha Melanocyte-stimulating hormone (alpha-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that alpha-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-alpha, IL 1beta, and IFN-gamma, in ocular surface of the dry eye rats. Moreover, alpha-MSH, at 10(-4) MUg/MUl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, alpha-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished alpha-MSH's protective effects, suggesting that both pathways are necessary for alpha-MSH's protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of alpha-MSH warrant translation of the alpha-MSH-containing eye drop into a novel and effective intervention to DED. PMID- 26685900 TI - A Novel Recombinant Enterovirus Type EV-A89 with Low Epidemic Strength in Xinjiang, China. AB - Enterovirus A89 (EV-A89) is a novel member of the EV-A species. To date, only one full-length genome sequence (the prototype strain) has been published. Here, we report the molecular identification and genomic characterization of a Chinese EV A89 strain, KSYPH-TRMH22F/XJ/CHN/2011, isolated in 2011 from a contact of an acute flaccid paralysis (AFP) patient during AFP case surveillance in Xinjiang China. This was the first report of EV-A89 in China. The VP1 coding sequence of this strain demonstrated 93.2% nucleotide and 99.3% amino acid identity with the EV-A89 prototype strain. In the P2 and P3 regions, the Chinese EV-A89 strain demonstrated markedly higher identity than the prototype strains of EV-A76, EV A90, and EV-A91, indicating that one or more recombination events between EV-A89 and these EV-A types might have occurred. Long-term evolution of these EV types originated from the same ancestor provides the spatial and temporal circumstances for recombination to occur. An antibody sero-prevalence survey against EV-A89 in two Xinjiang prefectures demonstrated low positive rates and low titres of EV-A89 neutralization antibody, suggesting limited range of transmission and exposure to the population. This study provides a solid foundation for further studies on the biological and pathogenic properties of EV-A89. PMID- 26685903 TI - Managing Your Own Mood Lability: Use of Mood Stabilizers and Antipsychotics in Pregnancy. AB - The management of psychiatric disorders during the perinatal period can be difficult; psychiatric decompensation during pregnancy can affect not only the mother but also the fetus and neonate. It is imperative that psychiatric providers proactively discuss pregnancy planning, and be able to thoughtfully weigh the risks of untreated psychiatric illness and psychotropic medications in pregnancy and breast-feeding. With the exception of valproate and carbamazepine, several mood stabilizers and antipsychotics can be utilized during pregnancy with minimal risk to the fetus and neonate in terms of major malformations; there is a growing body of evidence regarding the risk profile of use of these medications in pregnancy. Key Points Preconception planning is very helpful when it can be done; consider discussion and documentation of risks at time of administration of psychotropic medications for any reproductive-aged women, regardless of plans for conception. Continued psychiatric stability through the perinatal period is imperative; the risks of an untreated psychiatric disorder are just as important, if not more so important, than the risks of psychotropic medication exposure. Exposure to one psychotropic medication is safer than exposure to multiple medications. Utilize lowest effective dose of medication; most risks are not dose dependent, therefore would typically prefer higher dose of medication, rather than emergence of psychiatric symptoms, in order to avoid exposure of the fetus to both psychotropic medications and psychiatric symptoms. General recommendations are to avoid valproate and carbamazepine in reproductive-aged women. With close monitoring, lithium can be safely utilized in pregnancy. Preliminary data regarding use of atypical antipsychotics is reassuring in regards to major malformations; however, larger numbers of participants are needed to provide more complete reproductive safety data with this class. Clearly document risks of an untreated psychiatric illness as well as risks of psychotropic medication management to the mother and developing fetus/neonate. PMID- 26685901 TI - Enhanced Osteogenesis by Reduced Graphene Oxide/Hydroxyapatite Nanocomposites. AB - Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene based composite materials have potentials to stimulate osteogenesis. PMID- 26685904 TI - A randomised controlled trial of computerised cognitive behaviour therapy for the treatment of depression in primary care: the Randomised Evaluation of the Effectiveness and Acceptability of Computerised Therapy (REEACT) trial. AB - BACKGROUND: Computerised cognitive behaviour therapy (cCBT) has been developed as an efficient form of therapy delivery with the potential to enhance access to psychological care. Independent research is needed which examines both the clinical effectiveness and cost-effectiveness of cCBT over the short and longer term. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of cCBT as an adjunct to usual general practitioner (GP) care against usual GP care alone, for a free-to-use cCBT program (MoodGYM; National Institute for Mental Health Research, Australian National University, Canberra, Australia) and a commercial pay-to-use cCBT program (Beating the Blues((r)); Ultrasis, London, UK) for adults with depression, and to determine the acceptability of cCBT and the experiences of users. DESIGN: A pragmatic, multicentre, three-armed, parallel, randomised controlled trial (RCT) with concurrent economic and qualitative evaluations. Simple randomisation was used. Participants and researchers were not blind to treatment allocation. SETTING: Primary care in England. PARTICIPANTS: Adults with depression who scored >= 10 on the Patient Health Questionnaire-9 (PHQ-9). INTERVENTIONS: Participants who were randomised to either of the two intervention groups received cCBT (Beating the Blues or MoodGYM) in addition to usual GP care. Participants who were randomised to the control group were offered usual GP care. MAIN OUTCOME MEASURES: The primary outcome was depression at 4 months (PHQ-9). Secondary outcomes were depression at 12 and 24 months; measures of mental health and health-related quality of life at 4, 12 and 24 months; treatment preference; and the acceptability of cCBT and experiences of users. RESULTS: Clinical effectiveness: 210 patients were randomised to Beating the Blues, 242 patients were randomised to MoodGYM and 239 patients were randomised to usual GP care (total 691). There was no difference in the primary outcome (depression measured at 4 months) either between Beating the Blues and usual GP care [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.75 to 1.88] or between MoodGYM and usual GP care (OR 0.98, 95% CI 0.62 to 1.56). There was no overall difference across all time points for either intervention compared with usual GP care in a mixed model (Beating the Blues versus usual GP care, p = 0.96; and MoodGYM versus usual GP care, p = 0.11). However, a small but statistically significant difference between MoodGYM and usual GP care at 12 months was found (OR 0.56, 95% CI 0.34 to 0.93). Free-to-use cCBT (MoodGYM) was not inferior to pay-to-use cCBT (Beating the Blues) (OR 0.91, 90% CI 0.62 to 1.34; p = 0.69). There were no consistent benefits of either intervention when secondary outcomes were examined. There were no serious adverse events thought likely to be related to the trial intervention. Despite the provision of regular technical telephone support, there was low uptake of the cCBT programs. Cost-effectiveness: cost effectiveness analyses suggest that neither Beating the Blues nor MoodGYM appeared cost-effective compared with usual GP care alone. Qualitative evaluation: participants were often demotivated to access the computer programs, by reason of depression. Some expressed the view that a greater level of therapeutic input would be needed to promote engagement. CONCLUSIONS: The benefits that have previously been observed in developer-led trials were not found in this large pragmatic RCT. The benefits of cCBT when added to routine primary care were minimal, and uptake of this mode of therapy was relatively low. There remains a clinical and economic need for effective low-intensity psychological treatments for depression with improved patient engagement. TRIAL REGISTRATION: This trial is registered as ISRCTN91947481. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme. PMID- 26685905 TI - Still Large, but Narrowing: The Sizable Decline in Racial Neighborhood Inequality in Metropolitan America, 1980-2010. AB - Although residential segregation is known to have declined for some racial groups in America, much less is known about change in the relative socioeconomic quality of the neighborhoods where different racial and ethnic groups live. Using census data for 1980-2010, we find that the neighborhoods where whites and minorities reside have become more alike in terms of neighborhood poverty and median income, largely because whites now live in poorer neighborhoods and because African Americans live in less-poor neighborhoods. The narrowing of black-white neighborhood inequality since 1980 has been sizable, far exceeding the narrowing of Hispanic-white neighborhood inequality; nonetheless, despite blacks' relative gains, the disparity in black-white neighborhood economic conditions remains very large. Asian Americans, on the other hand, now reside in neighborhoods that are economically similar to the neighborhoods where whites reside. Regression analyses reveal that racial neighborhood inequality declined the most in U.S. metropolitan areas where racial residential segregation declined the most. PMID- 26685906 TI - Basic Psychological Need Satisfaction, Emotion Dysregulation, and Non-suicidal Self-Injury Engagement in Young Adults: An Application of Self-Determination Theory. AB - Non-suicidal self-injury (NSSI) is a public health concern that affects young adults at alarming rates. The present study examines the role of satisfaction of self-determination theory's three basic needs for autonomy, competence, and relatedness in young adults' NSSI engagement. University students who reported ever having engaged in NSSI (n = 40, 85 % female; Mage = 20.10, SD = 1.66) reported significantly lower levels of the satisfaction of all three needs, as well as more difficulties with all aspects of emotion regulation (non-acceptance of emotional responses, difficulty engaging in goal directed behavior, impulse control, lack of emotional awareness, limited access to regulation strategies, lack of emotional clarity), compared to students with no history of NSSI (n = 46, 91 % female; Mage = 19.79, SD = 1.37). Results of a logistic regression analysis revealed that need satisfaction added to the prediction of NSSI group membership after controlling for the effects of emotion regulation. Satisfaction of the need for competence and limited access to emotion regulation strategies accounted for significant variance in NSSI in the final model. The findings suggest that self determination theory may be a useful framework under which to conceptualize NSSI and that the need for competence may be particularly salient for University students. PMID- 26685902 TI - Hepatocytes: a key cell type for innate immunity. AB - Hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. Hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. These proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide signaling, and the coagulation factor fibrinogen that activates innate immunity. In this review, we summarize the wide variety of innate immunity proteins produced by hepatocytes and discuss liver-enriched transcription factors (e.g. hepatocyte nuclear factors and CCAAT/enhancer-binding proteins), pro-inflammatory mediators (e.g. interleukin (IL)-6, IL-22, IL-1beta and tumor necrosis factor-alpha), and downstream signaling pathways (e.g. signal transducer and activator of transcription factor 3 and nuclear factor-kappaB) that regulate the expression of these innate immunity proteins. We also briefly discuss the dysregulation of these innate immunity proteins in chronic liver disease, which may contribute to an increased susceptibility to bacterial infection in patients with cirrhosis. PMID- 26685907 TI - Language modulates brain activity underlying representation of kinship terms. AB - Kinship terms have been found to be highly diverse across languages. Here we investigated the brain representation of kinship terms in two distinct populations, native Chinese and Caucasian English speakers, with a five-element kinship identification (FEKI) task. The neuroimaging results showed a common extensive frontal and parietal lobe brain activation pattern for different kinship levels for both Chinese and Caucasian English speakers. Furthermore, Chinese speakers had longer reaction times and elicited more fronto-parietal brain networks activation compared to English speakers in level three (e.g., uncle and nephew) and four (e.g., cousin), including an association between the middle frontal gyrus and superior parietal lobe, which might be associated with higher working memory, attention control, and social distance representation load in Chinese kinship system processing. These results contribute to our understanding of the representation of kinship terms in the two languages. PMID- 26685909 TI - Introduction to the "Fellows and Young GIs Section". PMID- 26685910 TI - Tight Junction Ultrastructure Alterations in a Mouse Model of Enteral Nutrient Deprivation. AB - BACKGROUND: Total parenteral nutrition (TPN), a necessary treatment for patients who cannot receive enteral nutrition, is associated with infectious complications due in part to a loss of intestinal epithelial barrier function (EBF). Using a mouse model of TPN, with enteral nutrient deprivation, we previously demonstrated an increase in mucosal interferon-gamma and tumor necrosis factor-alpha; these cytokine changes are a major mediator driving a reduction in epithelial tight junction (TJ) protein expression. However, the exact ultrastructural changes to the intestinal epithelial barrier have not been previously described. AIM: We hypothesized that TPN dependence results in ultrastructural changes in the intestinal epithelial TJ meshwork. METHODS: C57BL/6 mice underwent internal jugular venous cannulation and were given enteral nutrition or TPN with enteral nutrient deprivation for 7 days. Freeze-fracture electron microscopy was performed on ileal tissue to characterize changes in TJ ultrastructure. EBF was measured using transepithelial resistance and tracer permeability, while TJ expression was measured via Western immunoblotting and immunofluorescence staining. RESULTS: While strand density, linearity, and appearance were unchanged, TPN dependence led to a mean reduction in one horizontal strand out of the TJ compact meshwork to a more basal region, resulting in a reduction in meshwork depth. These findings were correlated with the loss of TJ localization of claudin-4 and tricellulin, reduced expression of claudin-5 and claudin-8, and reduced ex vivo EBF. CONCLUSION: Tight junction ultrastructural changes may contribute to reduced EBF in the setting of TPN dependence. PMID- 26685908 TI - Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies. AB - Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing >= 45 vs. <5 g/day: advanced 0.83, 0.70-0.99; trend test p value 0.29), fatal, 0.69, 0.59 0.82, trend test p value 0.16). Participants who ate >= 25 versus <5 g/day of eggs (1 egg ~ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01-1.28, trend test p value 0.01; fatal 1.14, 1.00 1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. PMID- 26685911 TI - Pulmonary Crohn's Disease. PMID- 26685912 TI - Simulation of dental collisions and occlusal dynamics in the virtual environment. AB - Semi-adjustable articulators have often been used to simulate occlusal dynamics, but advances in intra-oral scanning and computer software now enable dynamics to be modelled mathematically. Computer simulation of occlusal dynamics requires accurate virtual casts, records to register them and methods to handle mesh collisions during movement. Here, physical casts in a semi-adjustable articulator were scanned with a conventional clinical intra-oral scanner. A coordinate measuring machine was used to index their positions in intercuspation, protrusion, right and left laterotrusion, and to model features of the articulator. Penetrations between the indexed meshes were identified and resolved using restitution forces, and the final registrations were verified by distance measurements between dental landmarks at multiple sites. These sites were confirmed as closely approximating via measurements made from homologous transilluminated vinylpolysiloxane interocclusal impressions in the mounted casts. Movements between the indexed positions were simulated with two models in a custom biomechanical software platform. In model DENTAL, 6 degree-of-freedom movements were made to minimise deviation from a straight line path and also shaped by dynamic mesh collisions detected and resolved mathematically. In model ARTIC, the paths were further constrained by surfaces matching the control settings of the articulator. Despite these differences, the lower mid-incisor point paths were very similar in both models. The study suggests that mathematical simulation utilising interocclusal 'bite' registrations can closely replicate the primary movements of casts mounted in a semi-adjustable articulator. Additional indexing positions and appropriate software could, in some situations, replace the need for mechanical semi-adjustable articulation and/or its virtual representation. PMID- 26685913 TI - Podocyte biology in 2015: New insights into the mechanisms of podocyte health. PMID- 26685916 TI - Stem cells and renal development in 2015: Advances in generating and maintaining nephron progenitors. PMID- 26685919 TI - Chronic kidney disease: Role of PTH/PTHrP receptor in cachexia. PMID- 26685920 TI - Glomerular disease: Addition of immunosuppression to supportive care does not STOP-IgAN. PMID- 26685921 TI - Regional brain dysregulation of Ca(2+)-handling systems in ketamine-induced rat model of experimental psychosis. AB - Chronic N-methyl-D-aspartate receptor (NMDAR) antagonist treatment can provide valuable neurochemical and neuroanatomical models of experimental psychosis. One such antagonist, ketamine, with its short half-time and well-documented psychotomimetic action, has cognitive effects resembling various aspects of schizophrenia-like symptoms. In order to obtain insights into possible relationships between Ca(2+) homeostasis and schizophrenia-related symptoms, we investigate the effects of chronic ketamine administration on intracellular Ca(2+) levels in various brain regions and on the expression level of key members of the neuronal Ca(2+)-handling system in rats. We show increased intracellular [Ca(2+)] in all of the examined brain regions following ketamine treatment but an altered cytosolic Ca(2+) level correlated with hyperlocomotor activity was only established for the cortex and striatum. Our findings also suggest that an imbalance in the expression between the calcium "on" and "off" systems contributes to the deregulation of brain Ca(2+) homeostasis in our ketamine induced model of experimental psychosis. Identification of the genes whose expression is affected by ketamine treatment indicates their involvement as putative etiological factors in schizophrenia. PMID- 26685922 TI - Rapid Reversible Photoswitching of Integrin-Mediated Adhesion at the Single-Cell Level. AB - Rapid and reversible photoswitching of cell adhesion is achieved by c(RGDfK) azobenzenes embedded in a poly(ethylene glycol) background on surfaces. The light induced cis-trans-isomerization of the azobenzene enables switching of cell adhesion on the surface. Reversibility of switching over several consecutive switching cycles is demonstrated by single-cell force spectroscopy. PMID- 26685923 TI - Yoga and compassion meditation program improve quality of life and self compassion in family caregivers of Alzheimer's disease patients: A randomized controlled trial. AB - AIM: To investigate the effects of the practice of yoga in combination with compassion meditation on the quality of life, attention, vitality and self compassion of family caregivers of patients with Alzheimer's disease. METHODS: A total of 46 volunteers were randomly allocated to two groups, the yoga and compassion meditation program group (n = 25), and the control group (CG) that received no treatment (n = 21). The program lasted 8 weeks, and comprised three yoga and meditation practices per week, with each session lasting 1 h and 15 min. Quality of life, attention, vitality, and self-compassion scores were measured pre- and postintervention. RESULTS: The yoga and compassion meditation program group showed statistically significant improvements (P < 0.05) on quality of life, attention, vitality and self-compassion scores as compared with the control group, which showed no statistical significant differences at the postintervention time-point. CONCLUSIONS: The findings of the present study suggest that an 8-week yoga and compassion meditation program can improve the quality of life, vitality, attention, and self-compassion of family caregivers of Alzheimer's disease patients. Geriatr Gerontol Int 2017; 17: 85-91. PMID- 26685924 TI - CT OF NASAL TURBINATES. PMID- 26685925 TI - Monitoring the effects of thiamethoxam applied as a seed treatment to winter oilseed rape on the development of bumblebee (Bombus terrestris) colonies. AB - BACKGROUND: The development of bumblebee (Bombus terrestris audax) colonies that had foraged for 5 weeks on flowering winter oilseed rape grown from seed treated with thiamethoxam (as Cruiser OSR) was assessed (two control, one treated field). Colony development was evaluated by monitoring the colony mass, forager activity was assessed, both at the hive and within the crop, and the contribution of oilseed rape to the pollen stored within the colony was analysed. RESULTS: Pollen collected from the treated crop contained residues of 1.0 ug thiamethoxam kg(-1) and 3.0 ug CGA322704 (metabolite likely equivalent to clothiandin) kg(-1) , and nectar contained residues of 1.8 ug thiamethoxam kg(-1) and no metabolite. No residues of thiamethoxam or CGA322704 were detected in samples from the control fields. Up to 93% of bumblebee collected pollen sampled from within the colonies originated from oilseed rape, and B. terrestris were observed actively foraging on all the fields. Colonies on all three fields showed similar rates of mass gain during the exposure phase and comparable production of gynes and drones. CONCLUSIONS: B. terrestris colonies placed adjacent to a field of flowering oilseed rape grown from thiamethoxam-treated seed developed at a comparable rate with colonies placed adjacent to oilseed rape grown from untreated seed. (c) 2015 Society of Chemical Industry. PMID- 26685926 TI - Host preferences in host-seeking and blood-fed mosquitoes in Switzerland. AB - The avian zoonotic agent for West Nile virus (WNV) can cause neuroinvasive disease in horses and humans and is expanding its range in Europe. Analyses of the risk for transmission to these hosts in non-endemic areas are necessary. Host preferences of mosquitoes (Diptera: Culicidae), the main vectors of WNV, were determined in Switzerland using animal-baited trap (horse, chickens) experiments at a natural and a periurban site. This was undertaken on four occasions during May-September 2014. In addition, the hosts of 505 blood-fed mosquitoes collected in a zoo and in the field were determined. Mosquito data obtained in the animal bait experiments were corrected for host weight and body surface area and by Kleiber's scaling factor. Collections of 11-14 different mosquito species were achieved with these approaches. Statistically significant host preferences were identified in three species in both approaches. The other species showed opportunistic feeding behaviours to varying extents. Specifically, the invasive species Hulecoeteomyia japonica (= Aedes japonicus) was identified for the first time as feeding on avians in nature. Abundance data, spatiotemporal activity and laboratory vector competence for WNV suggested that, in addition to the main WNV vector Culex pipiens, H. japonica and Aedimorphus vexans (= Aedes vexans) are the most likely candidate bridge vectors for WNV transmission in Switzerland. PMID- 26685927 TI - Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen's criteria. AB - OBJECTIVE: In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimer's disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM-5 (DSM-5-MCI) and Petersen's (P-MCI) criteria. METHOD: A population representative cohort of 4057 dementia-free individuals 55+ years of age was followed up at 2.5 and 4.5 years in Zaragoza, Spain (ZARADEMP). Using the Geriatric Mental State- AGECAT for assessment, research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. 'Conversion rate' (CR), 'annual conversion rate' (ACR), and incidence rate (IR) were calculated along with incidence rate ratio (IRR) to compare the performance of the intermediate cognitive definitions. RESULTS: At 4.5-year follow-up, in individuals aged 65+ years, ACRs for non-cases, P-MCI, and DSM-5-MCI were 0.8, 1.9 and 3.4, respectively, for global dementia. The IRRs were 2.9 and 5.3 for P-MCI and DSM5 MCI, respectively, being the non-cases the reference category. The corresponding values were slightly lower for AD. CONCLUSION: Conversion rate to dementia and AD was higher using DSM-5-MCI criteria than using Petersen's criteria. However, prediction of the construct still has some way to go, as most MCI individuals did not convert at 4.5-year follow-up. PMID- 26685929 TI - Using the Targeted Solutions Tool(r) to Improve Hand Hygiene Compliance Is Associated with Decreased Health Care-Associated Infections. AB - BACKGROUND: In 2010 Memorial Hermann Health System (MHHS) implemented the Joint Commission Center for Transforming Healthcare's (the Center's) Web-based Targeted Solutions Tool (r)(TST (r)) for improving hand hygiene through-out its 12 hospitals after participating in the Center's first project on hand hygiene, pilot testing the TST, and achieving significant improvement for each pilot unit. Because hand hygiene is a key contributing factor in health care-associated infections (HAIs), this project was an important part of MHHS's strategy to eliminate HAIs. METHODS: MHHS implemented the TST for hand hygiene in 150 inpatient units in 12 hospitals and conducted a system wide process improvement project from October 2010 through December 2014. The TST enabled MHHS to measure compliance rates, identify reasons for noncompliance, implement tested interventions provided by the TST, and sustain the improvements. Data on rates of ICU central line- associated bloodstream infections (CLABSIs) and ventilator- associated pneumonia (VAP) were also collected and analyzed. RESULTS: Based on 31,600 observations (October 2010- May 2011), MHHS's system wide hand hygiene compliance baseline rate averaged 58.1%. Compliance averaged 84.4% during the "improve" phase (June 2011-November 2012), 94.7% in the first 13 months of the "control phase" (December 2012-December 2014) and 95.6% in the final 12 months (p < 0.0001 for all comparisons to baseline). Con comitantly, adult ICU CLABSI and VAP rates decreased by 49% (p = 0.024) and 45% (p = 0.045), respectively. CONCLUSION: MHHS substantially improved hand hygiene compliance in its hospitals and sustained high levels of compliance for 25 months following implementation. Adult ICU CLABSI and VAP rates decreased in association with the hand hygiene compliance improvements. PMID- 26685928 TI - Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification. AB - Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. PMID- 26685930 TI - The Costs of Participating in a Diabetes Quality Improvement Collaborative: Variation Among Five Clinics. AB - BACKGROUND: Quality improvement collaboratives (QICs) support rapid testing and implementation of interventions through the collective experience of participating organizations to improve care quality and reduce costs. Although QICs have been societally cost-effective in improving the care of chronic diseases, they may not be adopted by outpatient clinics if their costs are high. Diabetes QICs warrant reexamination as secular trends in the quality of diabetes care, new care guidelines for diabetes, and evolving strategies for quality improvement may have altered implementation costs. METHODS: The costs over the first four years-from June 2009 through May 2013-of an ongoing diabetes QIC were characterized by activities and over time. The QIC, linking six clinics on Chicago's South Side, tailored interventions to minority populations and built community partnerships. Costs were calculated from clinic surveys regarding activities, labor, and purchases. RESULTS: Data were obtained from five of the six participating clinics. Cost/diabetic patient/year ranged across clinic sites from $6 (largest clinic) to $68 (smallest clinic). Clinics spent 62%-88% of their total QIC costs on labor. The cost/diabetic patient/year changed over time from Year 1 (range across clinics, $5-$51), Year 2 ($11-$84), Year 3 ($4-$57), to Year 4 ($4-$80), with costs peaking at Year 2 for all clinics except Clinic 4, where costs peaked at Year 4. DISCUSSION: Cost experiences of QICs in clinics were di- verse over time and setting. High per-patient costs may stem from small clinic size, a sicker patient population, and variation in personnel type used. Cost decreases over time may represent increasing organizational learning and efficiency. Sharing resources may have achieved additional cost savings. This practical information can help administrators and policy makers predict, manage, and support costs of QICs as payers increasingly seek high-value health care. PMID- 26685931 TI - A Tool for the Concise Analysis of Patient Safety Incidents. AB - BACKGROUND: Patient safety incidents, sometimes referred to as adverse events, incidents, or patient safety events, are too common an occurrence in health care. Most methods for incident analysis are time and labor intensive. Given the significant resource requirements of a root cause analysis, for example, there is a need for a more targeted and efficient method of analyzing a larger number of incidents. Although several concise incident analysis tools are in existence, there are no published studies regarding their usability or effectiveness. METHODS: Building on previous efforts, a Concise Incident Analysis (CIA) methodology and tool were developed to facilitate analysis of no- or low-harm incidents. Staff from 11 hospitals in five countries-Australia, Canada, Hong Kong, India, and the United States-pilot tested the tool in two phases. The tool was evaluated and refined after each phase on the basis of user perceptions of usability and effectiveness. RESULTS: From September 2013 through January 2014, 52 patient safety incidents were analyzed. A broad variety of incident types were investigated, the most frequent being patient falls (25%). Incidents came from a variety of hospital work areas, the most frequent being from the medical ward (37%). Most incidents investigated resulted in temporary harm or no harm (94%). All or most sites found the tool "understandable" (100%), "easy to use" (89%), and "effective" (89%). Some 95% of participants planned to continue to use all or some parts of the tool after the pilot. Qualitative feedback suggested that the tool allowed analysis of incidents that were not currently being analyzed because of insufficient resources. The tool was described as simple to use, easy to document, and aligned with the flow of the incident analysis. CONCLUSION: A concise tool for the investigation of patient safety incidents with low or no harm was well accepted across a select group of hospitals from five countries. PMID- 26685932 TI - Factors Associated with Inpatient Thoracentesis Procedure Quality at University Hospitals. AB - BACKGROUND: Physicians increasingly refer thoracentesis procedures to interventional radiology (IR) rather than performing them at the bedside. Factors associated with thoracentesis procedures at university hospitals were studied to determine clinical outcomes by provider specialty. METHODS: An administrative database review was performed of patients who underwent an inpatient thoracentesis procedure in hospitals participating in the University HealthSystem Consortium (UHC) Database from January 2010 through September 2013. The incidence of iatrogenic pneumothorax, mean total hospital costs, and mean length of stay (LOS) were compared by clinical specialty. RESULTS: There were 113,860 admissions with 132,472 thoracentesis procedures performed on 99,509 patients at 234 UHC hospitals. IR performed 43,783 (33%) thoracentesis procedures; medicine, 22,243 (17%); and pulmonary, 26,887 (20%). The incidence of iatrogenic pneumothorax was 2.8% for IR, 2.9% for medicine, and 3.1% for pulmonary. Medicine and pulmonary had equivalent risk of iatrogenic pneumothorax compared to IR after controlling for clinical covariates. Admissions with medicine and pulmonary procedures were associated with significantly lower costs compared to IR admissions (p < 0.001) after controlling for clinical covariates. Admissions with IR procedures had a mean LOS of 14.1 days; medicine, 13.2 days; and pulmonary, 15.9 days. Admissions with medicine and pulmonary procedures were associated with fewer hospital days when compared to IR in the controlled model (p < 0.001). CONCLUSION: Admissions with medicine and pulmonary bedside thoracentesis procedures are as safe and less costly than IR procedures. Shifting IR thoracentesis procedures to the bedside might be a potential way to reduce hospital costs while still ensuring high quality patient care, provided that portable ultrasound is used. PMID- 26685933 TI - Post Event Debriefs: A Commitment to Learning How to Better Care for Patients and Staff. PMID- 26685935 TI - Modeling anxiety in Parkinson's disease. AB - BACKGROUND: The aim of this work was to construct a model for anxiety in PD and compare the relative contributions of PD-specific and -nonspecific general population risk factors for anxiety in this model. METHODS: Structural equation modeling of associations of risk factors with the anxiety outcome using a cross sectional data set of 342 patients with PD were used. RESULTS: A model with acceptable to good fit was generated that explained 65% of the variance in anxiety scores. A previous history of depression and the severity of the depressive symptoms scored on the Hamilton Depression Rating Scale were the only nonspecific variables with a direct effect on anxiety. The presence of motor fluctuations and disease-related decline in activities of daily living were PD specific markers of anxiety. Nonspecific risk factors had a greater influence in the model than PD-specific risk factors. Standardized regression coefficients suggested that the Hamilton Depression Rating Scale score was the most important contributor to the variation in anxiety. A post-hoc analysis showed that the effects of the following variables on anxiety levels were fully mediated by depression: sex; family history of depression; previous history of anxiety; cognitive status; difficulties in non-disease-specific activities of daily living; and severity of motor signs. CONCLUSION: In this cross-sectional study, we showed that nonspecific general population risk factors are more important markers for anxiety than PD-specific risk factors. Depression was the most prominent marker. PD-specific markers for anxiety appear to be more situational and related to off periods and disease-specific disturbances of activities of daily living. PMID- 26685936 TI - Fast-track endovascular aneurysm repair: rationale and design of the multicenter Least Invasive Fast-Track EVAR (LIFE) registry. AB - BACKGROUND: Considerable technological advancements have recently been made with endovascular stent grafts for the treatment of abdominal aortic aneurysm (AAA). However, there is opportunity to further improve the efficiency of endovascular aneurysm repair (EVAR), which may yield better patient outcomes and lower perioperative treatment costs. METHODS/DESIGN: The Least Invasive Fast-Track EVAR (LIFE) registry was developed to determine the clinical utility and cost effectiveness of the Ovation(r) Prime stent graft when used under least invasive conditions using a defined fast-track protocol. The LIFE study is a prospective multicenter post-market registry of the ultra-low profile (14F) Ovation Prime stent graft when used in the treatment of patients with AAA using a fast-track protocol, consisting of appropriate patient selection, bilateral percutaneous access, avoidance of general anesthesia and intensive care unit admission, and next-day discharge. The primary endpoint of the study is the proportion of subjects that experience a major adverse event within 30 days of the initial procedure. Primary endpoint data will be compared to a target performance goal. A total of 250 subjects will be enrolled at up to 40 sites in the United States. The first subject in this study was enrolled in October 2014 and enrollment is anticipated to continue through mid-2016. DISCUSSION: The recent development of ultra low-profile stent grafts enables EVAR using least invasive methods. A structured fast-track EVAR protocol may yield clinical and cost benefits versus standard EVAR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224794. PMID- 26685937 TI - Improving the rate of negative margins after surgery for oral cavity squamous cell carcinoma: A prospective randomized controlled study. AB - BACKGROUND: A positive margin is among the most significant factors that affects the outcome in head and neck squamous cell carcinoma (SCC). The purpose of this study was to compare the negative margin rates between 2 methods of intraoperative margin assessment in patients with oral cavity SCC. METHODS: A prospective, randomized controlled trial comparing 2 methods of intraoperative margin assessment: specimen-driven margins and patient-driven margins. RESULTS: The final analysis included 71 patients, 20 (29%) in the patient-driven margin arm. Frozen section analysis revealed positive/close surgical margins that led to an extension of the surgical resection in 22 of 51 patients (43%) in the specimen driven margin arm, and 2 of 20 patients (10%) in the patient-driven margin arm (p = .01). After final pathological analysis, the wide negative margin rate was 84% in the specimen-driven margin arm, compared to 55% in the patient-driven margin arm (p = .02). Extension of the surgical resection prevented escalation of adjuvant treatment in 19 patients (38%) in the specimen-driven margin arm and 10% in the patient-driven margin arm. CONCLUSION: Specimen derived margin assessment led to significant improvement in the rate of negative margins. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1803-E1809, 2016. PMID- 26685970 TI - Multiple yielding processes in a colloidal gel under large amplitude oscillatory stress. AB - Fatigue refers to the changes in material properties caused by repeatedly applied loads. It has been widely studied for, e.g., construction materials, but much less has been done on soft materials. Here, we characterize the fatigue dynamics of a colloidal gel. Fatigue is induced by large amplitude oscillatory stress (LAOStress), and the local displacements of the gel are measured through high frequency ultrasonic imaging. We show that fatigue eventually leads to rupture and fluidization. We evidence four successive steps associated with these dynamics: (i) the gel first remains solid, (ii) it then slides against the walls, (iii) the bulk of the sample becomes heterogeneous and displays solid-fluid coexistence, and (iv) it is finally fully fluidized. It is possible to homogeneously scale the duration of each step with respect to the stress oscillation amplitude sigma0. The data are compatible with both exponential and power-law scalings with sigma0, which hints at two possible interpretations of delayed yielding in terms of activated processes or of the Basquin law. Surprisingly, we find that the model parameters behave nonmonotonically as we change the oscillation frequency and/or the gel concentration. PMID- 26685938 TI - Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions. AB - Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in >=80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation. PMID- 26685971 TI - Obesity and cardiovascular disease: friend or foe? AB - Obesity is currently one of the greatest public health issues worldwide. However, despite its known deleterious effects on the cardiovascular system and its association with numerous cardiovascular diseases (CVD), recent findings leading to the development of concepts such as metabolically healthy obesity, the obesity paradox, and protective subcutaneous fat depots have raised a lively debate on the disparate effects of obesity on health outcomes. Regarding the concept of metabolically healthy obesity, by presumably labelling a subset of obese people as metabolically healthy, physicians may not feel pressed to curb the current obesity epidemic and prevent the next generation of people from becoming obese. Another issue is that the most commonly used anthropometric index to define obesity, the body mass index, is at the core of the controversy because of its limitations including its inability to discriminate between fat mass and muscle mass. Many recent epidemiological and metabolic studies have used other indices such as waist-hip ratio, waist circumference, and imaging (computed tomography or magnetic resonance imaging) measurements of visceral adiposity and of ectopic fat depots. In addition, emerging evidence supports the importance of cardiorespiratory fitness, skeletal muscle mass and strength in patients with obesity as useful variables to predict CVD risk beyond adiposity. In this review, we will discuss the complex and disparate effects of obesity on CVD, particularly focusing on whether, under given circumstances, it could be harmful, potentially harmless or neutral, or even possibly protective. PMID- 26685972 TI - Risk stratification in non-ST elevation acute coronary syndromes: searching for the right formula. PMID- 26685974 TI - Radiolabelling with isotopic mixtures of (52g/55)Mn(II) as a straight route to stable manganese complexes for bimodal PET/MR imaging. AB - Radiolabelling using isotopic mixtures of (52g/55)Mn(ii) offers fast and easy access to new small molecule PET/MR tracers, composed of chemically identical reporting units. trans-1,2-Diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) was radiolabelled with carrier-added (52g)Mn(ii) in >99% radiochemical yield, producing the first manganese-based bimodal PET/MR probe. The Mn-CDTA chelate was shown to be very stable to air oxidation and sufficiently inert to decomplexation in blood serum. These data sparked our interest in functionalized CDTA ligands for the design of optimized PET/MR tracers. PMID- 26685975 TI - Using the MCoTI-II Cyclotide Scaffold To Design a Stable Cyclic Peptide Antagonist of SET, a Protein Overexpressed in Human Cancer. AB - The SET protein is a promising drug target in cancer therapy, because of its ability to inhibit the function of the tumor suppressor gene protein phosphatase 2A (PP2A). COG peptides, derived from apolipoprotein E (apoE), are potent antagonists of SET; they induce cytotoxicity in cancer cells upon binding to intracellular SET and modulate the nuclear factor kappa B (NF-kappaB) signaling pathway. However, the therapeutic potential of COG peptides is limited, because of their poor proteolytic stability and low bioavailability. In this study, the COG peptide, COG1410, was stabilized by grafting it onto the ultrastable cyclic peptide scaffold, Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II). The grafted MCoTI-II peptides were cytotoxic to a cancer cell line and showed high stability in human serum. The most potent grafted MCoTI-II peptide inhibited lipopolysaccharide (LPS)-mediated activation of NF-kappaB in murine macrophages. Overall, this study demonstrates the application of the MCoTI-II scaffold for the development of stable peptide drugs for cancer therapy. PMID- 26685976 TI - Healthcare Worker Perceptions of and Barriers to Universal Staphylococcal Decolonization in Elective Orthopaedic Joint Surgeries. PMID- 26685979 TI - The influence of sounds on posture control. AB - PURPOSE: It is still not clear which parameters of sound are the most significant for body reactions and whether the way of sound reception plays a role in body control. The purpose of this study was to determine the influence of frequency, spectrum and loudness of sounds on posture control in healthy women and men. METHODS: The study subjects were 29 young adults who were submitted to a 60 second standing test in the bipedal stance on the force platform (AMTI). During the tests, 3 sinusoidal sounds with various timing and 2 musical sounds (guitar and piano) of the frequency 225 Hz, 1000 Hz and 4000 Hz were applied through headphones. The centre of pressure (COP) amplitude was registered. The sway area and COP mean velocity were computed. RESULTS: It was found that high frequency sounds contributed to a significant decrease of sway area values. No significant influence of low frequency sounds on posture control was observed. The influence of the sound spectrum (timbre) on posture control is limited; only the crescendo spectrum improves the body stability in the bipedal stance and not the music spectrum as guitar and piano. The loudness of sound, although extremely high, is not the cause of postural control changing in relation to lower loudness. No effect of gender was found in terms of body stability under different sound conditions. CONCLUSION: Based on the results, it can be argued that, in general, in a bipedal stance in terms of stability high sound frequency improves posture control, whereas sound spectrum and intensity show a limited impact. PMID- 26685977 TI - Methylamine induced hypophagia is mediated via dopamine D1 and D2 receptors in neonatal meat chicks. AB - Recently, methylamine has been found as an endogenous amine, which is controlling food intake in mammals. However, there is no evidence about the effect of methylamine on feeding behavior in poultry. So, the present study was designed to evaluate the effect of intracerebroventricular (ICV) injection of methylamine and involvement of central methylamine/dopaminergic systems on feeding behavior in neonatal meat type chicks. In experiment 1, chicks were ICV injected with different doses of methylamine (0.48, 0.96, 1.44, 1.92 and 2.40 MUmol). In experiment 2, chicks received a dose of either the control solution, 2.40 MUmol methylamine, 125 nmol L-DOPA (dopamine precursor) or a combination of methylamine plus L-DOPA. Experiments 3-7 were similar to experiment 2 except that 150 nmol 6 OHDA (dopamine synthase inhibitor), 5 nmol SCH23390 (D1 receptor antagonist), 5 nmol AMI-193 (D2 receptor antagonist), 6.4 nmol NGB2904 (D3 receptor antagonist) and 6 nmol L-741, 742 (D4 receptor antagonist) were used instead of 125 nmol L DOPA, respectively. Cumulative food intake was determined until 2 h post injection. According to the results, methylamine significantly decreased food intake in a dose dependent manner (p < 0.05). The inhibitory effect of methylamine on food intake was significantly attenuated by 6-OHDA, SCH23390 and AMI-193 (P < 0.05), but NGB2904 and L-741, 742 had no effect on food intake induced by methylamine. In addition, hypophagic effect of methylamine significantly amplified by L-DOPA (P < 0.05). These results suggest that methylamine decrease food intake and there is an interaction between methylamine and dopaminergic system via D1 and D2 receptors in chickens. PMID- 26685978 TI - Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease. AB - BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb(-/-) mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb(-/-) colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb(-/-) rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb(-/-) aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb(-/-) HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies. PMID- 26685980 TI - Onlay parastomal hernia repair with cross-linked porcine dermal collagen biologic mesh: long-term results. AB - PURPOSE: The optimal technique and mesh type for parastomal hernia repair have yet to be ascertained. Biologic meshes have been advocated in parastomal hernia repair due to purported resistance to infection in contaminated fields. The aim of this study was to evaluate the effectiveness of additionally cross-linked acellular porcine dermal collagen mesh (Permacol) for onlay parastomal hernia repair. METHODS: A retrospective review of case notes, and abdominal CT scans when available, was performed for consecutive patients who had a parastomal hernia repaired between January 2007 and May 2010. All hernias were repaired with onlay placement of the biologic mesh. Hernias were classified according to the Moreno-Matias classification where CT scans were available. RESULTS: Over a 34 month period, 30 consecutive patients, median age 74 years, 17 female, underwent parastomal hernia repair using onlay biologic mesh. There were 23 paracolostomy and seven paraileostomy hernias. The hernia was primary in 26 patients. Pre operative CT scans were available in 18 patients (Moreno-Matias Type 1 = 1, Type 2 = 4, Type 3 = 13). There was one perioperative death, and 29 patients were available for follow-up, and median duration of follow-up (either CT or clinical) was 36 months (range 3-79). Twenty-six patients developed recurrence of the parastomal hernia (89.6%), and median time to recurrence was 10 months (range 3 72),with Moreno-Matias Type 1 = 0, Type 2 = 4, Type 3 = 14, unknown = 8. Fifteen out of 26 patients have had repairs of the recurrence using a variety of techniques. Of these, 10 patients have had further recurrence. CONCLUSION: Onlay repair of parastomal hernia with cross-linked porcine dermal collagen biologic mesh reinforcement has poor long-term outcomes with unacceptably high recurrence rates and should not be performed. PMID- 26685981 TI - Can ureteral stones cause pain without causing hydronephrosis? AB - INTRODUCTION: While computerized tomography (CT) is the gold standard for diagnosis of ureterolithiasis, ultrasound is a less costly and radiation-free alternative which is commonly used to evaluate patients with ureteral colic. The purpose of this study was to evaluate the frequency with which patients with ureteral stones and renal colic demonstrate hydronephrosis in order to better understand the evaluation of these patients. METHODS: Two hundred and forty-eight consecutive patients presenting with ureteral colic and diagnosed with a single unilateral ureteral stone on CT scan in an urban tertiary care emergency department were retrospectively reviewed. Radiology reports were reviewed for stone size, diagnosis, and degree of hydronephrosis. RESULTS: Of the 248 patients evaluated for suspected ureteral stone, 221 (89.1 %) demonstrated any hydronephrosis, while 27 (10.9 %) did not. Hydronephrosis grade, available in 194 patients, was as follows: mild-70.6 %, moderate-27.8 %, and severe-1.5 %. Mean patient age was 47.0 years (SD 15.5), gender distribution was 35.9 % female and 64.1 % male, and mean stone axial diameter was 4.1 mm (SD 2.4). Stone location was as follows: ureteropelvic junction-4.1 %, proximal ureter-21 %, distal ureter 24.9 %, and ureterovesical junction-47.1 %. Axial stone diameter and coronal length (craniocaudal) were both significant predictors of degree of hydronephrosis (ANOVA, p < 0.001 for both). Age (ANOVA, p = NS), stone location (Chi square, p = NS), and gender (Chi square, p = NS) were not associated with degree of hydronephrosis. CONCLUSIONS: In patients with ureteral stones and colic, nearly 11 % do not demonstrate any hydronephrosis and a majority (nearly 71 %) will demonstrate only mild hydronephrosis. Stone diameter appears to be related to degree of hydronephrosis, whereas age, gender, and stone location are not. The lower incidence of hydronephrosis for small stones causing renal colic may explain the lower diagnostic accuracy of ultrasound when compared to CT for detecting ureteral stones. PMID- 26685982 TI - Sexually Transmitted Infections and First Sexual Intercourse Age in Adolescents: The Nationwide Retrospective Cross-Sectional Study. AB - INTRODUCTION: Sexually transmitted infections (STIs) are major causes of medical and psychological problems globally, while adolescents in South Korea have recently shown rapid changes in sexual behaviors. AIMS: We aimed to examine the association between the age of first sexual intercourse and the experience of STIs among adolescents. Additionally, in which specific time period would more likely to get infected from sexual intercourse. METHODS: We used data from the 2007-2013 Korea Youth Risk Behavior Web-based Survey. Only adolescents with sexual intercourse experience (N = 22,381) were included, and multiple logistic regression analysis was performed. MAIN OUTCOME MEASURES: One dichotomized measure and one continuous measure were assessed: (i) STIs experience (defined as having had STIs); and (ii) association between STIs experience and absolute age gap (defined as temporal differences between secondary sexual character emergence age and first sexual intercourse age). RESULTS: Approximately 7.4% of boys and 7.5% of girls reported had STI. For both boys and girls, the chance of experiencing STIs increased as the age of first sexual intercourse decreased (boys: before elementary school [age 7 or under]: odds ratio [OR] = 10.81, first grade [age 7 or 8]: OR = 4.44, second grade [age 8 or 9]: OR = 8.90, fourth grade [age 10 or 11]: OR = 7.20, ninth grade [age 15 or 16]: OR = 2.31; girls: before elementary school: OR = 18.09, first grade: OR = 7.26, second grade: OR = 7.12, fourth grade: OR = 8.93, ninth grade: OR = 2.74). The association between the absolute age gap and STI experience was examined additionally (boys: OR = 0.93, girls: OR = 0.87). CONCLUSIONS: This study shows that earlier initiation of sexual intercourse increases the odds of experiencing STIs. Also as the age gap gets shorter, the odds of experiencing STIs increase. Our study suggests that it is important to consider the time period of first sexual intercourse and to reinforce a monitoring system along with the development of other preventive strategies. PMID- 26685983 TI - Enhanced Antitumor Activity of Cetuximab in Combination with the Jak Inhibitor CYT387 against Non-Small-Cell Lung Cancer with Various Genotypes. AB - Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is effective in the treatment of non-small-cell lung cancers (NSCLCs). However, resistance to EGFR inhibitors limits its effectiveness. In this study, we investigated the effectiveness of Jak-2 inhibitor, CYT387, in combination with cetuximab. Xenograft animal models were administered with cetuximab or CYT387 or their combination. It was observed that NSCLC cells exhibited enormous differences in responses to cetuximab; cell lines were more intrinsically resistant to cetuximab. In resistant cell lines (H1975 and H1650), the efficacy of cetuximab was increased when combined with CYT387, whereas CYT387 alone in low doses exhibited little effect on NSCLC cell proliferation. In addition, the antitumor activity of cetuximab was increased in H1975 resistant model in spite of low efficacy of cetuximab treatment alone in. Jak/STAT signaling was suppressed effectively by the combination of cetuximab and CYT387. In summary, our findings indicated that CYT387 has a potent indirect antitumor activity, and it is also synergistic in its activity in combination with cetuximab against NSCLC tumors, especially with cetuximab intrinsic-resistance tumors. These indications were mediated via Janus kinase (Jak)-signal transducer and transcription (STAT) pathway activator. Our results strongly and consistently supported the potential synergism of CYT387 as Jak inhibitor for anti-NSCLC therapy with EGFR-targeting agents. PMID- 26685984 TI - Immunohistochemical detection of a potential molecular therapeutic target for canine hemangiosarcoma. AB - Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm of dogs for which there is currently no effective treatment. A recent study suggested that receptor tyrosine kinases (RTKs), the PI3K/Akt/m-TOR and MAPK pathways are all activated in canine and human HSA. The aim of the present study was to investigate the overexpression of these proteins by immunohistochemistry in canine splenic HSA to identify potential molecular therapeutic targets. A total of 10 splenic HSAs and two normal splenic samples surgically resected from dogs were sectioned and stained with hematoxylin and eosin for histological diagnosis or analyzed using immunohistochemistry. The expression of RTKs, c-kit, VEGFR-2 and PDGFR-2, as well as PI3K/Akt/m-TOR and MEK was higher in canine splenic HSAs compared to normal spleens. These proteins may therefore be potential therapeutic targets in canine splenic HSA. PMID- 26685985 TI - Characterization of a human isolate of Tritrichomonas foetus (cattle/swine genotype) infected by a zoonotic opportunistic infection. AB - Tritrichomonas species flagellates (IMC strain) were isolated from the biliary tract of an individual who had developed cholecystitis as a complication of acquired agammaglobulinemia. Sequence analysis of Tritrichomonas sp. (IMC clone 2 (cl2)) was performed for several genetic regions including the ITS1-5.8S rDNA ITS2 region, the cysteine protease (CP)-1, CP-2 and CP-4 to CP-9 genes, and the cytosolic malate dehydrogenase 1 gene. In addition to comparison of the variable length DNA repeats in the isolate clone with those in T. foetus (Inui cl2) and the T. mobilensis (U.S.A.: M776 cl2) reference strains, this analysis showed that the Tritrichomonas sp. (IMC cl2) was T. foetus (cattle/swine genotype). Injection of T. foetus (IMC cl2) directly into the livers of CBA mice resulted in liver abscess formation on Day 7. Moreover, inoculation via orogastric intubation caused infection in the cecum on Day 5 in CBA mice co-infected with Entamoeba histolytica (HM-1: IMSS cl6). T. foetus (IMC cl2) was able to grow in YI-S medium for over 20 days, even at 5 degrees C. These results indicate that the T. foetus isolate is able to survive in the feces and edible organ meat of the definitive host for a prolonged period of time, and it is possible that the parasite could infect humans. PMID- 26685986 TI - Revival of "dead" memristive devices: case of WO3-x. AB - Inappropriate operation could make a memristive device "dead" and cause the loss of resistive switching performance. In this study, the revival of "dead" devices was investigated in the case of WO3-x-based memristive devices. It is believed that inappropriate operation with a high-voltage pulse creates an ordered structure of oxygen vacancies and such an ordered structure makes the normal reset process fail. By precisely controlled voltage sweeping at certain compliance currents, a "dead" device can be revived. The revival operation disrupts the ordered structure by Joule heating and recovers Schottky-like barrier modulation-based switching. PMID- 26685987 TI - Effect of viscosity on photodegradation rates in complex secondary organic aerosol materials. AB - This work explores the effect of environmental conditions on the photodegradation rates of atmospherically relevant, photolabile, organic molecules embedded in a film of secondary organic material (SOM). Three types of SOM were studied: alpha pinene/O3 SOM (PSOM), limonene/O3 SOM (LSOM), and aged limonene/O3 obtained by exposure of LSOM to ammonia (brown LSOM). PSOM and LSOM were impregnated with 2,4 dinitrophenol (2,4-DNP), an atmospherically relevant molecule that photodegrades faster than either PSOM or LSOM alone, to serve as a probe of SOM matrix effects on photochemistry. Brown LSOM contains an unidentified chromophore that absorbs strongly at 510 nm and photobleaches upon irradiation. This chromophore served as a probe molecule for the brown LSOM experiments. In all experiments, either the temperature or relative humidity (RH) surrounding the SOM films was varied. The extent of photochemical reaction in the samples was monitored using UV-vis absorption spectroscopy. For all three model systems examined, the observed photodegradation rates were slower at lower temperatures and lower RH, conditions that make SOM more viscous. Additionally, the activation energies for photodegradation of each system were positively correlated with the viscosity of the SOM matrix as measured in poke-flow experiments. These activation energies were calculated to be 50, 24, and 17 kJ mol(-1) for 2,4-DNP in PSOM, 2,4-DNP in LSOM, and the chromophore in brown LSOM, respectively, and PSOM was found to be the most viscous of the three. These results suggest that the increased viscosity is hindering the motion of the molecules in SOM and is slowing down their respective photochemical reactions. PMID- 26685988 TI - From DNA to catalysis: a thymine-acetate ligated non-heme iron(III) catalyst for oxidative activation of aliphatic C-H bonds. AB - A non-heme, iron(III)/THA(thymine-1-acetate) catalyst together with H2O2 as an oxidant is efficient in oxidative C-H activation of alkanes. Although having a higher preference for tertiary C-H bonds, the catalyst also oxidizes aliphatic secondary C-H bonds into carbonyl compounds with good to excellent conversions. Based on the site selectivity of the catalyst and our mechanistic studies the reaction proceeds via an Fe-oxo species without long lived carbon centered radicals. PMID- 26685989 TI - Supramolecular surface adhesion mediated by azobenzene polymer brushes. AB - Surface immobilised polymer brushes containing azobenzene units were prepared using a combination of microcontact chemistry and surface-initiated atom transfer radical polymerisation (SI-ATRP). These brushes were investigated using AFM, XPS and UV/vis spectroscopy. It was shown that two surfaces bearing azobenzene brushes can be glued together in the presence of a beta-cyclodextrin polymer and hold as much as 700 +/- 150 g cm(-2). PMID- 26685990 TI - Sex differences in the acquisition and maintenance of cocaine and nicotine self administration in rats. AB - RATIONALE: Consistent sex differences are observed in human drug addiction, with females often exceeding males on drug intake. However, there is still a need for animal models for some aspects of addiction such as acquisition of drug self administration and the subsequent development of drug-seeking. OBJECTIVES: The present study examined sex differences in the acquisition and maintenance of self administration of two widely used stimulants, cocaine and nicotine. METHODS: Male and female rats self-administered cocaine (0.4 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) daily under a fixed-ratio 1 (FR 1) schedule until acquisition criteria were met (maximum of 30 sessions). The self-administration criterion for cocaine was >=20 infusions in a 2-h session and >=5 infusions in a 1-h session for nicotine. Sex differences were assessed by examining the percentage of rats that met acquisition criteria, the number of sessions to meet criteria, and the number of infusions earned during the maintenance phase. RESULTS: A significantly higher percentage of male rats acquired both cocaine and nicotine self administration than females, and males met acquisition criteria in fewer sessions. However, after criteria were met, females self-administered more cocaine than males during the first 5 days of maintenance. There were no sex differences in nicotine infusions post-acquisition. CONCLUSIONS: Differences in acquisition amongst sexes can reveal factors that are integral to initiation of drug use, an often overlooked phase of drug addiction. PMID- 26685991 TI - The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats. AB - RATIONALE: Experimental evidence indicates that the non-competitive N-methyl-D aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain, and its abnormalities have been linked to schizophrenia. OBJECTIVES: The present study was designed to investigate the ability of the NO donor sodium nitroprusside (SNP) to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. METHODS: The ability of SNP to reverse ketamine induced memory deficits and social withdrawal were assessed using the novel object recognition task (NORT) and the social interaction test, respectively. Furthermore, since anxiety disorders are noted to occur commonly in schizophrenics, the effects of SNP on anxiety-like behaviour were examined using the light/dark test. Locomotor activity was also assessed as an independent measure of the potential motoric effects of this NO donor. RESULTS: SNP (0.3 and 1 mg/kg) reversed ketamine (3 mg/kg)-induced short-term recognition memory deficits. SNP (1 mg/kg) counteracted the ketamine (8 mg/kg)-induced social isolation in the social interaction test. The anxiolytic-like effects in the light/dark test of SNP (1 mg/kg) cannot be attributed to changes in locomotor activity. CONCLUSIONS: Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia like behavioural deficits. The data also suggest a role of NO in anxiety. PMID- 26685992 TI - Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment. AB - RATIONALE: Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. OBJECTIVE: Assess the role of the amygdala in emotional responses. METHODS: Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. RESULTS: After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. CONCLUSIONS: The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation. PMID- 26685993 TI - Reverse Engineering and Evaluation of Prediction Models for Progression to Type 2 Diabetes: An Application of Machine Learning Using Electronic Health Records. AB - BACKGROUND: Application of novel machine learning approaches to electronic health record (EHR) data could provide valuable insights into disease processes. We utilized this approach to build predictive models for progression to prediabetes and type 2 diabetes (T2D). METHODS: Using a novel analytical platform (Reverse Engineering and Forward Simulation [REFS]), we built prediction model ensembles for progression to prediabetes or T2D from an aggregated EHR data sample. REFS relies on a Bayesian scoring algorithm to explore a wide model space, and outputs a distribution of risk estimates from an ensemble of prediction models. We retrospectively followed 24 331 adults for transitions to prediabetes or T2D, 2007-2012. Accuracy of prediction models was assessed using an area under the curve (AUC) statistic, and validated in an independent data set. RESULTS: Our primary ensemble of models accurately predicted progression to T2D (AUC = 0.76), and was validated out of sample (AUC = 0.78). Models of progression to T2D consisted primarily of established risk factors (blood glucose, blood pressure, triglycerides, hypertension, lipid disorders, socioeconomic factors), whereas models of progression to prediabetes included novel factors (high-density lipoprotein, alanine aminotransferase, C-reactive protein, body temperature; AUC = 0.70). CONCLUSIONS: We constructed accurate prediction models from EHR data using a hypothesis-free machine learning approach. Identification of established risk factors for T2D serves as proof of concept for this analytical approach, while novel factors selected by REFS represent emerging areas of T2D research. This methodology has potentially valuable downstream applications to personalized medicine and clinical research. PMID- 26685994 TI - A Digital Ecosystem of Diabetes Data and Technology: Services, Systems, and Tools Enabled by Wearables, Sensors, and Apps. AB - The management of type 1 diabetes (T1D) ideally involves regimented measurement of various health signals; constant interpretation of diverse kinds of data; and consistent cohesion between patients, caregivers, and health care professionals (HCPs). In the context of myriad factors that influence blood glucose dynamics for each individual patient (eg, medication, activity, diet, stress, sleep quality, hormones, environment), such coordination of self-management and clinical care is a great challenge, amplified by the routine unavailability of many types of data thought to be useful in diabetes decision-making. While much remains to be understood about the physiology of diabetes and blood glucose dynamics at the level of the individual, recent and emerging medical and consumer technologies are helping the diabetes community to take great strides toward truly personalized, real-time, data-driven management of this chronic disease. This review describes "connected" technologies--such as smartphone apps, and wearable devices and sensors--which comprise part of a new digital ecosystem of data-driven tools that can link patients and their care teams for precision management of diabetes. These connected technologies are rich sources of physiologic, behavioral, and contextual data that can be integrated and analyzed in "the cloud" for research into personal models of glycemic dynamics, and employed in a multitude of applications for mobile health (mHealth) and telemedicine in diabetes care. PMID- 26685995 TI - Remote Health Consultations Supported by a Diabetes Management Web Application With a New Glucose Meter Demonstrates Improved Glycemic Control. AB - BACKGROUND: Cloud-connected diabetes applications enable health care professionals (HCPs) to monitor patient progress and offer the potential for remote consultations. OneTouch Reveal (OTR) is a cloud-based web application that aggregates data from blood glucose (BG) meters or insulin pumps and provides analytics to help patients and HCPs make more informed treatment and lifestyle decisions. This study assessed the experience of patients using OTR and the OneTouch Verio (OTV) BG meter and determined the extent of changes in glycemic control. METHODS: Subjects with T1DM (23) or T2DM (17) uploaded BG meter results to OTR for 12 weeks. HCPs remotely reviewed progress using OTR and delivered telephone consultations at 4 and 8 weeks based on OTR insights. RESULTS: After 12 weeks, mean HbA1c decreased by 0.4% (P < .001) and 25% of subjects had a reduction of >=1.0%. Reduction in HbA1c was similar in subjects with T1DM and T2DM, although subjects with T1DM started with higher baselines. In subjects with T2DM, mean BG decreased significantly from 175 to 161 mg/dl (P < .001) with the percentage of above-range BG results decreasing from 33% to 24%. 80% of subjects confirmed OTR detected out-of-range glucose patterns and 84% of these subjects were able to correct the underlying pattern to get BG back in-range. CONCLUSIONS: OTR web application in combination with the OTV meter helped subjects with T1DM and T2DM effectively manage their diabetes and was associated with improved BG control over 12 weeks. Real-time visibility to subject data may help HCPs deliver focused and effective remote consultations. PMID- 26685996 TI - Interface and Strain Energy Revolution Texture Map To Predict Structure and Optical Properties of Sputtered PbSe Thin Films. AB - The preferred growth orientation of the sputtered lead selenide (PbSe) thin films on Si(100) substrates was thermodynamically simulated and calculated on the basis of the density functional theory. The results showed that the total free energy variation during the grain growth is dominated by the interface and strain energy minimization under certain conditions, indicating that the preferred growth orientation and related optical properties of the PbSe thin films can be effectively modified by these two energy variations. Thermodynamically, the PbSe[200] and PbSe[220] preferred orientations are obtained when the interface and strain energy minimization dominate the total free energy variation, respectively. A texture map related to the interface and strain energy revolution was obtained, which can be used to predict the structure and optical properties of the sputtered PbSe thin films, and its applicability was confirmed by the real X-ray diffraction and Fourier transform infrared spectroscopy experimental results of four midfrequency sputtered PbSe thin films with designed thickness and microstrain deposited on Si(100) substrates. PMID- 26685997 TI - Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions. AB - Heteronuclear and homonuclear direct (D) and indirect (J) spin-spin interactions are important sources of structural information about nucleic acids (NAs). The Hamiltonians for the D and J interactions have the same functional form; thus, the experimentally measured apparent spin-spin coupling constant corresponds to a sum of J and D. In biomolecular NMR studies, it is commonly presumed that the dipolar contributions to Js are effectively canceled due to random molecular tumbling. However, in strong magnetic fields, such as those employed for NMR analysis, the tumbling of NA fragments is anisotropic because the inherent magnetic susceptibility of NAs causes an interaction with the external magnetic field. This motional anisotropy is responsible for non-zero D contributions to Js. Here, we calculated the field-induced D contributions to 33 structurally relevant scalar coupling constants as a function of magnetic field strength, temperature and NA fragment size. We identified two classes of Js, namely (1)JCH and (3)JHH couplings, whose quantitative interpretation is notably biased by NA motional anisotropy. For these couplings, the magnetic field-induced dipolar contributions were found to exceed the typical experimental error in J-coupling determinations by a factor of two or more and to produce considerable over- or under-estimations of the J coupling-related torsion angles, especially at magnetic field strengths >12 T and for NA fragments longer than 12 bp. We show that if the non-zero D contributions to J are not properly accounted for, they might cause structural artifacts/bias in NA studies that use solution NMR spectroscopy. PMID- 26685998 TI - Male meiosis in Crustacea: synapsis, recombination, epigenetics and fertility in Daphnia magna. AB - We present the first detailed cytological study of male meiosis in Daphnia (Crustacea: Branchiopoda: Cladocera)-an aquatic microcrustacean with a cyclical parthenogenetic life cycle. Using immunostaining of the testes in Daphnia magna for baseline knowledge, we characterized the different stages of meiotic division and spermiogenesis in relation to the distribution of proteins involved in synapsis, early recombination events and sister chromatid cohesion. We also studied post-translational histone modifications in male spermatocytes, in relation to the dynamic chromatin progression of meiosis. Finally, we applied a DNA fragmentation test to measure sperm quality of D. magna, with respect to levels of inbreeding. As a proxy for fertility, this technique may be used to assess the reproductive health of a sentinel species of aquatic ecosystems. Daphnia proves to be a model species for comparative studies of meiosis that is poised to improve our understanding of the cytological basis of sexual and asexual reproduction. PMID- 26685999 TI - Formation of Nup98-containing nuclear bodies in HeLa sublines is linked to genomic rearrangements affecting chromosome 11. AB - Nup98 is an important component of the nuclear pore complex (NPC) and also a rare but recurrent target for chromosomal translocation in leukaemogenesis. Nup98 contains multiple cohesive Gly-Leu-Phe-Gly (GLFG) repeats that are critical notably for the formation of intranuclear GLFG bodies. Previous studies have reported the existence of GLFG bodies in cells overexpressing exogenous Nup98 or in a HeLa subline (HeLa-C) expressing an unusual elevated amount of endogenous Nup98. Here, we have analysed the presence of Nup98-containing bodies in several human cell lines. We found that HEp-2, another HeLa subline, contains GLFG bodies that are distinct from those identified in HeLa-C. Rapid amplification of cDNA ends (RACE) revealed that HEp-2 cells express additional truncated forms of Nup98 fused to a non-coding region of chromosome 11q22.1. Cytogenetic analyses using FISH and array-CGH further revealed chromosomal rearrangements that were distinct from those observed in leukaemic cells. Indeed, HEp-2 cells feature a massive amplification of juxtaposed NUP98 and 11q22.1 loci on a chromosome marker derived from chromosome 3. Unexpectedly, minor co-amplifications of NUP98 and 11q22.1 loci were also observed in other HeLa sublines, but on rearranged chromosomes 11. Altogether, this study reveals that distinct genomic rearrangements affecting NUP98 are associated with the formation of GLFG bodies in specific HeLa sublines. PMID- 26686001 TI - Sensitivity of proxies on non-linear interactions in the climate system. AB - Recent climate change is affecting the earth system to an unprecedented extent and intensity and has the potential to cause severe ecological and socioeconomic consequences. To understand natural and anthropogenic induced processes, feedbacks, trends, and dynamics in the climate system, it is also essential to consider longer timescales. In this context, annually resolved tree-ring data are often used to reconstruct past temperature or precipitation variability as well as atmospheric or oceanic indices such as the North Atlantic Oscillation (NAO) or the Atlantic Multidecadal Oscillation (AMO). The aim of this study is to assess weather-type sensitivity across the Northern Atlantic region based on two tree ring width networks. Our results indicate that nonstationarities in superordinate space and time scales of the climate system (here synoptic- to global scale, NAO, AMO) can affect the climate sensitivity of tree-rings in subordinate levels of the system (here meso- to synoptic scale, weather-types). This scale bias effect has the capability to impact even large multiproxy networks and the ability of these networks to provide information about past climate conditions. To avoid scale biases in climate reconstructions, interdependencies between the different scales in the climate system must be considered, especially internal ocean/atmosphere dynamics. PMID- 26686000 TI - Biofunctionalization of Selenium Nanoparticle with Dictyophora Indusiata Polysaccharide and Its Antiproliferative Activity through Death-Receptor and Mitochondria-Mediated Apoptotic Pathways. AB - Bio-functionalized nanoparticles with semiconducting/metallic core encapsulated in a bio- or bio-derived materials are promising for applications in biology and especially in cancer diagnostic and healing. In this report, we report a facile, single-step, first-time synthesis and in-situ functionalization strategy for the preparation of monodispersed selenium nanoparticles (SeNPs) functionalized using a novel polysaccharide (DP1) extracted from Dictyophora indusiata (a fungus). The DP1 functionalized SeNPs (DP1-SeNPs), where DP1 is attached to the surface via Se O bond as well as physic-sorption had, an average diameter of 89 nm, and were highly uniform, extremely stable compared to bare SeNPs. Detailed investigation of the biological properties of DP1-SeNP illustrated that they exhibit unprecedented, enhanced, and selective antiproliferative activity through inducing cell apoptosis confirmed by nuclear condensation, DNA cleavage, and accumulation of S phase cell arrest. The mechanism of the induced apoptosis was found to be a combination of the activation of caspases 3, 8, and 9, the Fas associated death domain protein (FADD), reactive oxygen species (ROS) overproduction, as well as mitochondrial dysfunction. It is envisioned that the reported DP1-SeNPs will offer a new phase space for high-efficiency anticancer treatment with little side effect. PMID- 26686002 TI - Tracking of abdominal subcutaneous and preperitoneal fat mass during childhood. The Generation R Study. AB - BACKGROUND: Overweight and obesity in early life tends to track into later life. Not much is known about tracking of abdominal fat. Our objective was to examine the extent of tracking of abdominal fat measures during the first six years of life. DESIGN: We performed a prospective cohort study among 393 Dutch children followed from the age of 2 years (90% range 1.9; 2.3) until the age of 6 years (90% range 5.7; 6.2). At both ages, we performed abdominal ultrasound to measure abdominal subcutaneous and preperitoneal fat distances and areas, and we calculated the preperitoneal/subcutaneous fat distance ratio. High abdominal fat measures were defined as values in the upper 15%. RESULTS: Abdominal subcutaneous fat distance and area, and preperitoneal fat area at 2 years were correlated with their corresponding measures at 6 years (all P-values <0.01), with the strongest coefficients for abdominal subcutaneous fat measures. Preperitoneal fat distance at the age of 2 years was not correlated with the corresponding measure at 6 years. The tracking coefficient for preperitoneal/subcutaneous fat distance ratio from 2 to 6 years was r=0.36 (P<0.01). Children with high abdominal subcutaneous fat measures at 2 years had increased risk of having high abdominal subcutaneous fat measures at 6 years (odds ratios 9.2 (95% confidence interval (CI) 4.1-20.8) and 12.4 (95% CI 5.4-28.6) for subcutaneous fat distance and area, respectively). These associations were not observed for preperitoneal fat measures. CONCLUSIONS: Our findings suggest that both abdominal subcutaneous and preperitoneal fat mass measures track during childhood, but with stronger tracking for abdominal subcutaneous fat measures. An adverse abdominal fat distribution in early life may have long-term consequences. PMID- 26686003 TI - Capsaicinoids: a spicy solution to the management of obesity? AB - Capsaicin is the molecule that is responsible for the pungency of hot peppers. It stimulates the sympathoadrenal system that mediates the thermogenic and anorexigenic effects of capsaicinoids. Capsaicinoids have been found to accentuate the impact of caloric restriction on body weight loss. Some studies have also shown that capsinoids, the non-pungent analogs of capsaicinoids, increase energy expenditure. Capsaicin supplementation attenuates or even prevents the increase in hunger and decrease in fullness as well as the decrease in energy expenditure and fat oxidation, which normally result from energy restriction. These effects may postpone the occurrence of resistance to lose fat during a weight loss program and facilitate the maintenance of body weight in a postobese state. Evidence also highlights the plausibility of an indirect effect of capsaicin on energy balance via its analgesic effects, which may improve sleep and ultimately facilitate the regulation of energy balance. Although capsaicin intake appears to be a safe practice, further studies will be needed to ascertain the safety of regular long-term consumption. Taken together, these observations reinforce the idea that consumption of capsaicinoids and capsinoids may be helpful to facilitate obesity management. PMID- 26686005 TI - What is the meaning of "reasonable medical certainty"? Your guess is as good as mine. PMID- 26686004 TI - Systematic review and meta-analysis of the effect of meal intake on postprandial appetite-related gastrointestinal hormones in obese children. AB - Understanding the physiological response to meal intake, of gut-derived appetite and satiety hormone signals, in obese compared with healthy-weight children may assist with informing strategies to help curtail the obesity epidemic. A systematic review and meta-analysis of studies investigating the acute postprandial response of gastrointestinal appetite hormones to meal intake in obese children was undertaken. Systematic searches of databases EMBASE, CINAHL Plus, OVID Medline and the Cochrane Library were performed. INCLUSION CRITERIA: a randomised controlled trial or experimental cross-sectional study following an acute test meal protocol with pre- and postprandial analysis of plasma or serum gastrointestinal hormone concentrations. Database searching retrieved 1001 papers for review. Nine studies met the inclusion criteria, collectively reporting on six appetite hormones yielding a total of 32 test meal-hormone comparisons. Meta analyses compared the pooled estimate of the mean difference of the postprandial change in total ghrelin and total peptide YY (PYY). Obese compared with healthy weight children had an attenuated change in ghrelin at 60 min (N=5 studies; n=129 participants) and 120 min postprandial (N=4 studies; n=100 participants) (P<0.05 for both time points). Obese compared with healthy-weight children also had an attenuated PYY response at 60 min (N=5 studies; n=128 participants) and 120 min postprandial (N=4 studies; n=100 participants). Insufficient studies reported on the postprandial time course of other appetite-related hormones, precluding a meta-analysis. Limited evidence notwithstanding, these findings indicate that PYY and ghrelin responses to a meal may be altered in obese children. This review has also identified a major gap in knowledge of hormonal appetite responses in childhood obesity. More comprehensive investigations of the homoeostatic regulation of gut-derived appetite and satiety hormone signals with behavioural and clinical outcomes are warranted to understand if there are consequences of these differences. PMID- 26686006 TI - The unreasonableness of 'reasonable medical certainty'. PMID- 26686007 TI - The yield of mechanically harvested rapeseed (Brassica napus L.) can be increased by optimum plant density and row spacing. AB - To determine the effects of plant density and row spacing on the mechanical harvesting of rapeseed (Brassica napus L.), field experiments were conducted. Higher plant density produced fewer pods and reduced the yield per plant. Wider row spacing at higher plant densities increased seeds per pod and the 1000-seed weight, resulting in a higher yield per plant. The highest yields were achieved at a density of 45 * 10(4) plants ha(-1) (D45) in combination with 15 cm row spacing (R15) because mortality associated with competition increased as both the plant density and row spacing increased. The leaf area index (LAI) and pod area index (PAI) showed similar relations to the yield per hectare, and they were positively correlated with the percentage of intercepted light, whereas the radiation use efficiency (RUE) was positively correlated with population biomass. Reduced plant height and increased root/shoot ratios led to a decreased culm lodging index. Improved resistance to pod shattering was also observed as plant density and row spacing increased. The angle of the lowest 5 branches decreased as row spacing increased under D30 and D45. All of these structural changes influenced the mechanical harvesting operations, resulting in the highest yield of mechanically harvesting rapeseed under D45R15. PMID- 26686008 TI - The effects of host-feeding on stability of discrete-time host-parasitoid population dynamic models. AB - Discrete-time models are the traditional approach for capturing population dynamics of a host-parasitoid system. Recent work has introduced a semi-discrete framework for obtaining model update functions that connect host-parasitoid population levels from year-to-year. In particular, this framework uses differential equations to describe the host-parasitoid interaction during the time of year when they come in contact, allowing specific behaviors to be mechanistically incorporated. We use the semi-discrete approach to study the effects of host-feeding, which occurs when a parasitoid consumes a potential host larva without ovipositing. We find that host-feeding by itself cannot stabilize the system, and both populations exhibit behavior similar to the Nicholson-Bailey model. However, when combined with stabilizing mechanisms such as density dependent host mortality, host-feeding contracts the region of parameter space that allows for a stable host-parasitoid equilibrium. In contrast, when combined with a density-dependent parasitoid attack rate, host-feeding expands the non zero equilibrium stability region. Our results show that host-feeding causes inefficiency in the parasitoid population, which yields a higher population of hosts per generation. This suggests that host-feeding may have limited long-term impact in terms of suppressing host levels for biological control applications. PMID- 26686009 TI - Formation of naturally occurring pigments during the production of nitrite-free dry fermented sausages. AB - This study investigates the potential of producing red coloured dry fermented sausages without the addition of nitrite and/or nitrate. Therefore, the formation of zinc protoporphyrin IX (Zn(II)PPIX) as naturally occurring pigment, and the interrelated protoporphyrin IX (PPIX) and heme content were evaluated during nitrite-free dry fermented sausage production at different pH conditions. Zn(II)PPIX was only able to form in dry fermented sausages at pH conditions higher than approximately 4.9. Additionally, the presence of Zn(II)PPIX increased drastically at the later phase of the production process (up to day 177), confirming that in addition to pH, time is also a crucial factor for its formation. Similarly, PPIX also accumulated in the meat products at increased pH conditions and production times. In contrast, a breakdown of heme was observed. This breakdown was more gradual and independent of pH and showed no clear relationship with the formed amounts of Zn(II)PPIX and PPIX. A statistically significant relationship between Zn(II)PPIX formation and product redness was established. PMID- 26686010 TI - Kids are not just little people: Pediatric versus adult dermatology approaches to skin diseases. Part I. PMID- 26686011 TI - Atopic dermatitis: Kids are not just little people. AB - The approach to children and adults with atopic dermatitis is similar. In both age groups, failure to respond to conventional therapy should prompt evaluation for complicating factors such as secondary infection and secondary ACD. Immunologic, metabolic, genetic, and nutritional disorders should be considered in the differential diagnosis of refractory pediatric atopic dermatitis. Cutaneous T cell lymphoma (CTCL), cutaneous drug reactions, other spongiotic dermatoses, psoriasis, dermatomycosis, and infestations should be considered in the differential of refractory atopic dermatitis in adults. Systemic therapies prescribed to both children and adults with severe atopic dermatitis include oral corticosteroids, cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil. PMID- 26686012 TI - Allergic contact dermatitis: Kids are not just little people. AB - Over the last ten years, there has been an increased awareness of allergic contact dermatitis (ACD) in children, in addition to adults. Historically, ACD was not considered a significant disease in the pediatric population. This may have been due to failure to employ patch testing, which is the gold standard for establishing a diagnosis of ACD. A number of epidemiologic studies now reflect upon the significance of positive patch tests in children and its utility in diagnosing ACD. While there is significant overlap among the most common allergens in children and adults, the patterns of exposure and sources of allergens can significantly differ, because children have distinct experiences related to their exposure to personal care products, articles of clothing, and time spent in play as opposed to work. Evaluation of the pediatric patient with dermatitis involves specialized knowledge in taking the pediatric history and specific techniques employed for successful patch test application. PMID- 26686013 TI - Trichodystrophies: A hair-raising differential diagnosis. AB - The appearance of an individual's hair is said to be reflective of internal health. Patients with hair shaft disorders commonly present with fragile, lusterless, sparse hair in addition to psychosocial distress. Hair shaft disorders may be hereditary or acquired and may present in children or adults. Due to the varied presentations, the differential diagnosis for hair is broad and often confusing. The authors present a question-by-question guide to help clinicians arrive at the correct diagnosis. PMID- 26686014 TI - Alopecia: Kids are not just little people. AB - Alopecia is a disorder that affects all patients, young and old. Many diagnoses, particularly the scarring alopecias, are more common in adults; however, others, such as tinea capitis, are more common in children, and some, such as alopecia areata, often affect both age groups. The approach to, and evaluation of, an alopecia patient is thus highly dependent on his or her age. In adults with diffuse, non-scarring hair loss, a part-width examination can help detect pattern hair loss, the most common cause of diffuse loss in this age group. In children this is much less likely, and a careful evaluation for tinea capitis is in order. The same holds true for patchy alopecia in children, as well as scarring alopecia tinea needs to always be considered. In adults, patchy alopecia is often due to alopecia areata and sometimes to one of the primary scarring alopecias. A laboratory evaluation, and especially a biopsy, would be a more appropriate undertaking for an adult than a child, and an adult would be more likely to tolerate certain therapeutic regimens such as intralesional injections. In a conversational manner, the authors discuss their individual approaches to the alopecia patient, highlighting the differences in diagnosis, workup, and management that depend on whether the affected individual is an adult or a child. PMID- 26686015 TI - Lichen planus and other lichenoid dermatoses: Kids are not just little people. AB - Lichenoid dermatoses, a group of inflammatory skin conditions with characteristic clinical and histopathologic findings, range from common to rare. Classic lichen planus typically presents as pruritic, polygonal, violaceous flat-topped papules and plaques; many variants in morphology and location also exist. Other lichenoid dermatoses share similar clinical presentations and histopathologic findings. These include lichenoid drug eruption, lichen planus-like keratosis, lichen striatus, lichen nitidus, and keratosis lichenoides chronica. Epidemiologic characteristics vary among each lichenoid disorder. While classic lichen planus is considered a disease of adults, other lichenoid dermatoses may be more common in younger populations. The literature contains an array of reports on the variations in presentation and successful management of lichen planus and lichenoid dermatoses among diverse populations. Familiarity with the characteristics of each lichenoid dermatosis, rare or common within each patient population, is key to accomplishing timely recognition and effective management. PMID- 26686016 TI - Bullous diseases: Kids are not just little people. AB - Bullous diseases may be rare; however, this does not preclude the clinician from being familiar with their manifestations and treatment. After ruling out infection, genetically inherited blistering diseases are more likely to be the cause of blistering or erosions in the neonatal period, whereas immunobullous diseases are more common in adults. Published literature on immunobullous disorders reflects information gleaned from case reports and open-label case series; prospective studies and evidence-based treatments are limited. Although there may be overlapping clinical features, significant clinical differences exist between adults and children. Evidence-based treatment guidelines are limited, and information from the adult literature cannot be readily generalized to the pediatric population. This paper reviews the approach to blistering conditions and the differences among bullous pemphigoid, linear immunoglobulin A disease, dermatitis herpetiformis, pemphigus foliaceus, pemphigus vulgaris, and paraneoplastic pemphigus in adult versus pediatric patients. PMID- 26686017 TI - Cutaneous infectious diseases: Kids are not just little people. AB - The changes in immune response that occur with age play a significant role in disease presentation and patient management. Evolution of the innate and adaptive immune systems throughout life, influenced partly by hormonal changes associated with puberty, plays a role in the differences between pediatric and adult response to disease. We review a series of manifestations of dermatologic infectious diseases spanning bacterial, viral, and fungal origins that can be seen in both pediatric and adult age groups and highlight similarities and differences in presentation and disease course. Therapeutic options are also discussed for these infectious diseases, with particular attention to variations in management between these population subgroups, given differences in pharmacokinetics and side effect profiles. PMID- 26686018 TI - Phototherapy: Kids are not just little people. AB - Phototherapy is the delivery of treatments in the form of visible or ultraviolet light for the therapeutic care of a patient. Usage of phototherapy in children is affected by limited data in the medical literature, the inability of some children to stand still during the delivery of therapy, parental concerns regarding risks of therapy, and scheduling difficulties. Despite the limitation of data, there are publications in support of usage of phototherapy, especially for psoriasis, atopic dermatitis, and vitiligo in both children and adults. This contribution provides an overview of the utility of phototherapy in skin conditions with a specific focus on the differences that exist in the data on and the delivery of phototherapy for adults and children. PMID- 26686019 TI - Laser therapy in dermatology: Kids are not just little people. AB - Advances in laser research and technology have led to expanded laser applications for the treatment of dermatologic disease. Lasers are viable treatment modalities for patients of any age group and offer unique treatment options for both adult and pediatric patients. While many skin diseases can be treated similarly in children and adults, differences in treatment approaches can result from varying anxiety levels, pain tolerance, psychosocial considerations of untreated disease, determination of suitable anesthesia, the use of size-appropriate safety equipment, and differences in the evolution of skin disease over time. Laser therapy can prove effective for the treatment of molluscum contagiosum unresponsive to conventional therapy. Hypertrophied vascular lesions and pigmented lesions, such as the nevus of Ota, respond more effectively to laser therapy earlier in life with fewer treatment sessions and reduced side effects. In the case of port-wine stains, the pulsed dye laser is the agent of choice in the pediatric patient, while the Q-switched alexandrite may be more effective in the adult population. PMID- 26686020 TI - Beyond diagnosis and treatment: How simple reassurance makes all the difference. AB - In life there are some people who are confident enought that they do not require reassurance and then there are others that need it constantly just to be able to function in their daily living. I am fortunate enough to experience the gift of reassurance and being able to give it back. As a first time mother, many of the experiences were unnerving and it was reassuring to hear someone say that I was doing a good job. We were also lucky to have a pediatrician who put our parenteral paranoia at ease by keeping communication open. She didn't always have the answers to every query, but she called and followed up and was able to send us to specialists who she could pass on the estafet of proving care. Now as a healthprovider myself I always try to have a conversation with my patients and their relatives about their and their loved ones treatment. I know that people are often reassured just by the knowledge that someone listened. PMID- 26686021 TI - On the skin of a soldier: The story of flogging. AB - After Farrier-Major Critton struck the 150th lash on the back of Private Frederick John White, at the end of a common disciplinary session at Hounslow Barracks, West London, in 1846, the soldier, whistling, walked himself to the infirmary to have his wounds dressed. His skin healed promptly, but 4 weeks later, he was found dead in his dormitory. The army medical officers, after performing an autopsy, reached the conclusion that the soldier had died from inflammation of internal organs but excluded any connection with flogging. This version of facts did not convince the coroner for Middlesex, who decided to open an inquest. After 3 more weeks of inquiry and 2 more postmortem examinations, the famous dermatologist Erasmus Wilson contradicted the army officers by affirming that the soldier had indeed died from the effects of flogging as the analysis of the cutaneous lesions and underneath would demonstrate. This contribution will detail how the inquest into the death of Private John White sparked a medical debate on the effects of military flogging to the skin. The discussion raised by the publication of the details of the autopsies demonstrated that different and opposing points of view coexisted in the Victorian period concerning the relation between external lacerations and internal organs in cases of flogging. PMID- 26686022 TI - Subcutaneous administration of methotrexate at high doses makes a better performance in the treatment of rheumatoid arthritis compared with oral administration of methotrexate: A systematic review and meta-analysis. AB - OBJECTIVES: This study was conducted to determine whether subcutaneous (SC) methotrexate (MTX) makes better performance on bioavailability, clinical efficiency, side effects occurrence, and treatment failure in the treatment of RA compared with oral MTX. METHODS: The databases PubMed, Web of Science, Embase, and Cochrane Library were systematically searched. Seven studies involving 1335 patients were eligible for data extraction and meta-analysis. The outcomes of meta-analysis were presented as mean difference (MD) or odd ration (OR) with 95% confidence interval (95% CI). RESULTS: Meta-analysis showed that SC MTX can significantly increase the AUC0-t (area under plasma concentration curve from administration to last observed concentration at time t) (MD = 506.84; 95% CI: 80.80-932.89), shorten the time to reach maximum observed concentration (Tmax) (MD = -0.13; 95% CI: -0.25 to -0.01) and the apparent terminal elimination half life (t(1/2)) (MD = -0.39; 95% CI: -0.70 to -0.08), reduce the occurrence of nausea (OR = 0.53; 95% CI: 0.28-0.97) and diarrhea (OR = 0.43; 95% CI: 0.20 0.95), improve the American College of Rheumatology criteria for 20% improvement (ACR20) (OR = 1.68; 95% CI: 1.09-2.61) and ACR70 (OR = 1.52; 95% CI: 1.02-2.26), and relieve the pain (MD = -0.65; 95% CI: -0.93 to -0.37) compared with oral MTX. However, the differences in maximum plasma concentration (Cmax), the occurrence of headache, vomiting and dyspepsia, ACR50, treatment failure were not significant between the two groups. CONCLUSION: SC route of MTX at high doses made better performance on improving the bioavailability and clinical efficacy, reducing the GI disorders, but it cannot decrease the treatment failure when compared with oral administration of MTX. PMID- 26686023 TI - Tissue-engineered conduit promotes sciatic nerve regeneration following radiation induced injury as monitored by magnetic resonance imaging. AB - PURPOSE: To observe the longitudinal changes in peripheral nerve repaired with chitosan conduits in a rat model of radiation-induced neuropathy. MATERIALS AND METHODS: Four months after 40 Gy radiation to the right lower limbs, forty-two rats were divided randomly into three groups. Chitosan conduits were implanted with (group A, n=12) or without (group B, n=12) mesenchymal stem cells (MSCs), and untreated controls (group C, n=12). Following sciatic nerve MR imaging (including T2WI and Gd-DTPA enhanced T1WI), functional evaluation and electrophysiological exam were performed two-monthly, final histological assessments were done at the end of one year. The differences among the experimental and control groups were statistically analysed with Fisher's PLSD or t-test. RESULTS: The compound muscle action potentials (CMAPs) and sciatic function index (SFI) had declined since 4 months after radiation injury. The focal nerve enlargement and hyperintensity, the perineurium and connecting muscle enhancement were demonstrated by MR neurography images. After chitosan tube implantation, the normalized signal intensities (SIs) in group A were declined more rapidly than SIs in other groups. The histological assessments indicated that group A had better remyelination, combined with higher CMAPs amplitude and SFI score than other groups. CONCLUSION: A single fraction dose of 40 Gy can be used to establish a rat model of sciatic nerve injury. Longitudinal electrophysiological examination and MR neurography are useful to evaluate the post-irradiation sciatic neuropathy. The rats with tissue-engineered conduits implantation showed some improvement of lower limb function, accompanied by a normalization of (T1W/T2W) MR signal. PMID- 26686025 TI - Meta analysis identifies a novel susceptibility locus associated with heel bone strength in the Korean population. AB - INTRODUCTION: Calcaneal quantitative ultrasound has been recognized as a non invasive method for evaluation of bone strength and prediction of osteoporotic fracture. METHODS: To extend a thorough genetic catalog for osteoporotic bone properties, we performed a genome-wide association study (rural cohort I, n=1895) of speed of sound (SOS) using the 1000 genome-based imputation in the discovery stage and then carried out in silico lookups (rural cohort II and III, n=2,967) and de novo genotyping (rural cohort IV, n=4,296) in the replication stage. RESULTS: In the combined meta-analysis (n=9,158), we identified a novel variant associated with SOS (rs2445771 in the GLDN gene, P=2.27*10(-9)) reaching genome wide significance in the Korean population. We further demonstrated that allele specific regulatory modifications found to be associated with functional enrichments by ENCODE annotations. CONCLUSION: Our findings could provide additional insights into understanding of genetic and epigenetic regulations on bone metabolism. PMID- 26686026 TI - Muslim patients' expectations and attitudes about Ramadan fasting during pregnancy. AB - OBJECTIVE: To investigate Muslim women's attitudes concerning Ramadan fasting during pregnancy and determine how healthcare providers can better serve this population. METHODS: A cross-sectional study targeted Muslim patients with active obstetric records within the University of Michigan Health System who received care at clinics in metro Detroit (MI, USA) during Ramadan in 2013. Patients aged 18-50 years were approached between July 7 and August 15, and asked to complete a written survey on perceptions of fasting, influences on decision making, and healthcare expectations. RESULTS: Among the 37 women who completed the survey, 26 (70%) did not fast in their current or most recent pregnancy during Ramadan. Overall, 23 (62%) women believed that fasting was harmful to themselves, their fetus, or both. Seven (19%) women reported consulting others about fasting during pregnancy, with the most influential individuals being Muslim scholars, followed by family/relatives and healthcare providers. The most important characteristics desired in a physician included being respectful of Islamic beliefs and possessing knowledge about Ramadan. CONCLUSION: Most women chose not to fast during pregnancy. Although few consulted healthcare providers, pregnant Muslim women valued their opinions. Healthcare providers need to educate themselves about which topics to discuss with Muslim patients to provide care on an individual basis. PMID- 26686024 TI - Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. AB - Cellular senescence permanently arrests cell proliferation, often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Loss of mitochondrial function can drive age-related declines in the function of many post-mitotic tissues, but little is known about how mitochondrial dysfunction affects mitotic tissues. We show here that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm. Cells that underwent mitochondrial dysfunction-associated senescence (MiDAS) had lower NAD+/NADH ratios, which caused both the growth arrest and prevented the IL-1 associated SASP through AMPK-mediated p53 activation. Progeroid mice that rapidly accrue mtDNA mutations accumulated senescent cells with a MiDAS SASP in vivo, which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture. Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes. PMID- 26686027 TI - A literature review of quantitative indicators to measure the quality of labor and delivery care. AB - BACKGROUND: Strengthening measurement of the quality of labor and delivery (L&D) care in low-resource countries requires an understanding of existing approaches. OBJECTIVES: To identify quantitative indicators of L&D care quality and assess gaps in indicators. SEARCH STRATEGY: PubMed, CINAHL Plus, and Embase databases were searched for research published in English between January 1, 1990, and October 31, 2013, using structured terms. SELECTION CRITERIA: Studies describing indicators for L&D care quality assessment were included. Those whose abstracts contained inclusion criteria underwent full-text review. DATA COLLECTION AND ANALYSIS: Study characteristics, including indicator selection and data sources, were extracted via a standard spreadsheet. MAIN RESULTS: The structured search identified 1224 studies. After abstract and full-text review, 477 were included in the analysis. Most studies selected indicators by using literature review, clinical guidelines, or expert panels. Few indicators were empirically validated; most studies relied on medical record review to measure indicators. CONCLUSIONS: Many quantitative indicators have been used to measure L&D care quality, but few have been validated beyond expert opinion. There has been limited use of clinical observation in quality assessment of care processes. The findings suggest the need for validated, efficient consensus indicators of the quality of L&D care processes, particularly in low-resource countries. PMID- 26686028 TI - Composite time-lapse computed tomography and micro finite element simulations: A new imaging approach for characterizing cement flows and mechanical benefits of vertebroplasty. AB - Vertebroplasty has been shown to reinforce weak vertebral bodies and reduce fracture risks, yet cement leakage is a major problem that can cause severe complications. Since cement flow is nearly impossible to control during surgery, small volumes of cement are injected, but then mechanical benefits might be limited. A better understanding of cement flows within bone structure is required to further optimize vertebroplasty and bone augmentation in general. We developed a novel imaging method, composite time-lapse CT, to characterize cement flow during injection. In brief, composite-resolution time-lapse CT exploits the qualities of microCT and clinical CT. The method consists in overlaying low resolution time-lapse CT scans acquired during injection onto pre-operative high resolution microCT scans, generating composite-resolution time-lapse CT series of cement flow within bone. In this in vitro study, composite-resolution time-lapse CT was applied to eight intact and five artificially fractured cadaveric vertebrae during vertebroplasty. The time-lapse scans were acquired at one milliliter cement injection steps until a total of 10 ml cement was injected. The composite-resolution series were then converted into micro finite element models to compute strains distribution under virtual axial loading. Relocation of strain energy density within bone structure was observed throughout the progression of the procedure. Interestingly, the normalized effect of cement injection on the overall stiffness of the vertebrae was similar between intact and fractured specimens, although at different orders of magnitude. In conclusion, composite time-lapse CT can picture cement flows during bone augmentation. The composite images can also be easily converted into finite element models to compute virtual strain distributions under loading at every step of an injection, providing deeper understanding on the biomechanics of vertebroplasty. PMID- 26686029 TI - Detection of the first OCA6 Italian patient in a large cohort of albino subjects. PMID- 26686030 TI - Fluorine nuclear magnetic resonance-based assay in living mammalian cells. AB - Nuclear magnetic resonance (NMR)-based screening has been recognized as a powerful approach for the identification and characterization of molecules interacting with pharmaceutical targets. Indeed, several NMR methods have been developed and successfully applied to many drug discovery projects. Whereas most of these approaches have targeted isolated biomolecular receptors, very few cases are reported with the screening performed in intact cells and cell extracts. Here we report the first successful application of the fluorine NMR-based assay n-FABS (n-fluorine atoms for biochemical screening) in living mammalian cells expressing the membrane protein fatty acid amide hydrolase (FAAH). This method allows the identification of both weak and potent inhibitors and the measurement of their potency in a physiological environment. PMID- 26686031 TI - Flow injection amperometric detection of insulin at cobalt hydroxide nanoparticles modified carbon ceramic electrode. AB - Cobalt hydroxide nanoparticles were prepared onto a carbon ceramic electrode (CHN|CCE) using the cyclic voltammetry (CV) technique. The modified electrode was characterized by X-ray diffraction and scanning electron microscopy. The results showed that CHN with a single-layer structure was uniformly electrodeposited on the surface of CCE. The electrocatalytic activity of the modified electrode toward the oxidation of insulin was studied by CV. CHN|CCE was also used in a homemade flow injection analysis system for insulin determination. The limit of detection (signal/noise [S/N] = 3) and sensitivity were found to be 0.11 nM and 11.8 nA/nM, respectively. Moreover, the sensor was used for detection of insulin in human serum samples. This sensor showed attractive properties such as high stability, reproducibility, and high selectivity. PMID- 26686032 TI - AIDS cholangiopathy visualized by single-operator cholangioscopy. PMID- 26686033 TI - Thromboembolism: an under appreciated cause of death. PMID- 26686034 TI - The overlooked COST of multiple myeloma. PMID- 26686035 TI - Eltrombopag in patients with high-risk myelodysplastic syndrome or acute myeloid leukaemia: cautious optimism. PMID- 26686036 TI - Aging and transplanting graciously. PMID- 26686037 TI - G6PD deficiency: a polymorphism balanced by heterozygote advantage against malaria. PMID- 26686038 TI - Adaptive cancer treatment: why I put my money on immunotherapy. PMID- 26686039 TI - INWORKS study: risk of leukaemia from protracted radiation exposure. PMID- 26686040 TI - INWORKS study: risk of leukaemia from protracted radiation exposure. PMID- 26686041 TI - INWORKS study: risk of leukaemia from protracted radiation exposure - Authors' reply. PMID- 26686042 TI - Financial toxicity in insured patients with multiple myeloma: a cross-sectional pilot study. AB - BACKGROUND: Financial toxicity is increasingly recognised as adversely affecting the quality of life and medication adherence in patients with cancer in the USA. Patients with multiple myeloma might be particularly vulnerable because of high use of novel treatments and extended treatment duration. METHODS: Between Aug 18, 2014, and Jan 7, 2015, we did a cross-sectional survey of individuals receiving at least 3 months of ongoing treatment for multiple myeloma at a tertiary academic medical centre in the USA. The survey was derived from previous reported studies and included the 11-item COST measure (financial toxicity score range 0 44). A paper survey was offered to eligible patients on arrival for routine follow-up visits, and participants were asked to complete the survey before or after their visit to the clinic. Insurance and treatment data were obtained from patients' electronic health records. FINDINGS: Of 111 patients approached for the study, 100 individuals completed the survey. 59 (59%) of 100 patients reported that treatment costs were higher than expected, 70 (71%) of 99 had at least minor financial burden, and 36 (36%) of 100 reported applying for financial assistance. Use of savings to pay for myeloma treatment was common (43 [46%] of 94 patients) and 21 (21%) of 98 individuals borrowed money to pay for medications. COST scores were highly correlated with patient-reported use of strategies to cope with myeloma treatment expenses. On multivariable analysis, younger age (correlation coefficient beta 0.36, 95% CI 0.15 to 0.56, p=0.00092), non-married status (5.6, 1.5 to 9.6, p=0.0074), longer duration since diagnosis (-4.8, -9.3 to -0.2, p=0.042), and lower household income (US$40 000-79 999: 7.8, 2.7 to 12.9, p=0.0031; >=$80 000: 11.8, 7.1 to 16.4, p<0.0001) were associated with higher financial burden as measured with the COST score. INTERPRETATION: Patient reported financial toxicity and use of coping mechanisms were common in our insured population with multiple myeloma. Additional attention to rising treatment costs and cost sharing is needed to address the increasing evidence of financial toxicity affecting patients with cancer. FUNDING: University of Pennsylvania Perelman School of Medicine. PMID- 26686043 TI - Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. AB - BACKGROUND: Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity. We aimed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome, secondary acute myeloid leukaemia after myelodysplastic syndrome, or de-novo acute myeloid leukaemia. METHODS: We did this multicentre, randomised, placebo controlled, double-blind, phase 1/2 trial at 37 centres in ten countries in Europe, east Asia, and the Americas. Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for standard treatments; had platelet counts of less than 30 * 10(9) platelets per L; had 10-50% bone-marrow blasts; or were platelet transfusion dependent were randomly assigned (2:1), via a telephone-based interactive voice-response system (GlaxoSmithKline Registration and Medication Ordering System) with a permuted-block randomisation schedule (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg. Randomisation was stratified by presence of poor-prognosis (complex) karyotype (presence of at least three abnormalities, or chromosome 7 abnormalities, vs absence) and bone-marrow blast count (<20% vs >=20%). Patients and study personnel were masked to treatment allocation. The primary endpoint was safety and tolerability, including adverse events, non-haematological laboratory grade 3-4 toxic effects, and changes in bone-marrow blast counts from baseline. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00903422. FINDINGS: Between May 14, 2009, and May 9, 2013, we randomly assigned 98 patients to receive either eltrombopag (n=64) or placebo (n=34). 63 (98%) patients in the eltrombopag group and 32 (94%) patients in the placebo group had adverse events. The most common adverse events were pyrexia (27 [42%] vs 11 [32%]), nausea (20 [31%] vs 7 [21%]), diarrhoea (19 [30%] vs 6 [18%]), fatigue (16 [25%] vs 6 [18%]), decreased appetite (15 [23%] vs 5 [15%]), and pneumonia (14 [22%] vs 8 [24%]). Drug-related adverse events of grade 3 or higher were reported in six (9%) patients in the eltrombopag group and four (12%) patients in the placebo group. Increases in the proportion of peripheral blasts did not differ significantly between groups. Haemorrhage of grade 3 or higher was reported in ten (16%) patients given eltrombopag and nine (26%) patients given placebo. 21 (33%) patients receiving eltrombopag and 16 (47%) patients receiving placebo died while on treatment. No deaths in patients receiving eltrombopag and two deaths in patients receiving placebo were regarded as treatment related. Post-baseline bone-marrow examinations were done in 40 (63%) patients in the eltrombopag group and 17 (50%) patients in the placebo group. The most common reason for no examination was death before the scheduled 3 month assessment. There were no differences between median bone-marrow blast counts or proportions of peripheral blasts between groups. INTERPRETATION: Eltrombopag doses up to 300 mg daily had an acceptable safety profile in patients with advanced myelodysplastic syndrome or acute myeloid leukaemia. The role of eltrombopag in these patients warrants further investigation. FUNDING: GlaxoSmithKline. PMID- 26686044 TI - Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis. AB - BACKGROUND: Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older. METHODS: For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis. FINDINGS: 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0.71 [95% CI 0.53-0.95], p=0.017) compared with non-allogeneic HSCT post-remission therapies or no post remission therapy, especially in patients with intermediate-risk (0.82 [0.58 1.15]) or adverse-risk (0.39 [0.21-0.73]) acute myeloid leukaemia. INTERPRETATION: Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study. FUNDING: None. PMID- 26686046 TI - Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. AB - BACKGROUND: Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured, despite initial treatment with R-CHOP. The prognostic importance of the revised International Prognostic Index (R-IPI) and cell of origin of the malignant B cell are established in DLBCL. We aimed to develop a novel, easily applicable, tissue based prognostic biomarker based on quantification of the tumour microenvironment that is independent of and additive to the R-IPI and cell of origin. METHODS: We performed digital hybridisation on the NanoString platform to assess the relation between immune effector and inhibitory (checkpoint) genes in 252 formalin-fixed, paraffin-embedded DLBCL tissue specimens obtained from patients treated with R CHOP. We used a tree-based survival model to quantify net antitumoral immunity (using ratios of immune effector to checkpoint genes) and to generate a cutoff as an outcome predictor in 158 of the 252 patients. We validated this model in tissue (n=233) and blood (n=140) samples from two independent cohorts treated with R-CHOP. FINDINGS: T-cell and NK-cell immune effector molecule expression correlated with tumour-associated macrophage and PD-1/PD-L1 axis markers, consistent with malignant B cells triggering a dynamic checkpoint response to adapt to and evade immune surveillance. The ratio of CD4*CD8 to (CD163:CD68[M2])*PD-L1 was better able to stratify overall survival than was any one immune marker or combination, distinguishing groups with disparate 4-year overall survival. 94 (59%) of 158 patients had a score above the cutoff and 4 year overall survival of 92.1% (95% CI 82.9-96.7), and the remaining 64 (41%) patients had a score below the cutoff and 4-year overall survival of 47.0% (32.8 60.5; hazard ratio [HR] 8.3, 95% CI 4.3-17.3; p<0.0001). The CD4*CD8:M2*PD-L1 immune ratio was independent of and added to the R-IPI and cell of origin. Tissue findings in the independent tissue cohort accorded with those in our initial tissue cohort. 139 (60%) of 233 patients had a score above the cutoff and 4-year overall survival of 75.6% (95% CI 64.6-83.6), with the remaining 94 (40%) patients having a score below the cutoff (63.5% [52.5-72.7]; HR 1.9, 95% CI 1.1 3.3; p=0.0067). INTERPRETATION: Ratios of immune effectors to checkpoints augment the cell of origin and R-IPI in DLBCL and are applicable to paraffin-embedded biopsy specimens. These findings might have potential implications for selection of patients for checkpoint blockade within clinical trials. FUNDING: Leukaemia Foundation of Queensland, Kasey-Anne Oklobdzijato Memorial Fund, the Australasian Leukaemia and Lymphoma Group (Malcolm Broomhead Bequest), the Australian Cancer Research Foundation, and the Cancer Council of Queensland. PMID- 26686047 TI - Altered FGF signalling in congenital craniofacial and skeletal disorders. AB - The fibroblast growth factor (FGF) signalling pathway has been the focus of intense genetic and functional research for several decades. The emerging data implicate FGF signalling in diverse regulatory processes, both in the developing embryo as well as in the adult organism. Alterations in this tightly regulated pathway can lead to a number of pathological conditions, ranging from well recognized congenital disorders to cancer. In order to mediate their cellular processes, FGFs signal through a subfamily of tyrosine kinase receptors, called FGF receptors (FGFRs). In humans, four FGFRs are described, and, to date, mutations in FGFR1, FGFR2, and FGFR3 have been shown to underlie human developmental disorders. FGFs/FGFRs are known to be key players in both endochondral and intramembranous bone development. In this review, we focus on the major developmental craniofacial and skeletal disorders which result from altered FGF signalling. PMID- 26686049 TI - Indian diabetes risk score and clustering of metabolic syndrome phenotype in a rural community of Asian Indian origin. AB - AIMS: This study was aimed at finding out the efficacy of Indian Diabetes Risk Score (IDRS) in identifying the individuals with increased risk of developing metabolic syndrome (MS) phenotype. METHODS: A total of 1007 (645 males and 362 females) rural participants aged >= 20 years took part in the study. Anthropometric measures and blood pressure were collected using standard techniques. Metabolic profiles and insulin were also estimated and HOMA-IR was calculated accordingly. RESULTS: There existed significant differences by IDRS categories for waist circumference, waist-hip ratio, waist-height ratio, body mass index, percentage body fat, sum of four skinfolds, total cholesterol, triglycerides, high, low and very low density lipoprotein cholesterol, fasting blood glucose, insulin, insulin resistance, systolic and diastolic blood pressure and mean arterial pressure. Significant (p<0.001) age group differences were also evident for IDRS categories. Remarkably higher prevalence of MS was observed with increasing IDRS. CONCLUSION: IDRS could be used to identify the individuals with increased risk of developing MS phenotype in this population. PMID- 26686050 TI - Pentacyclic triterpenes grafted on CD cores to interfere with influenza virus entry: A dramatic multivalent effect. AB - Multivalent effect plays an important role in biological processes, particularly in the specific recognition of virus with its host cell during the first step of infection. Here we report the synthesis of multivalent pentacyclic triterpene grafted on cyclodextrin core and potency of against influenza entry activity. Nine star-shaped compounds containing six, seven and eight pentacyclic triterpene pharmacophore on cyclodextrin scaffold were prepared by way of copper-catalyzed azide-alkyl cycloaddition reaction under microwave activation. Some of the multimers exhibited much potent antiviral activity against H1N1 virus (A/WSN/33), even equivalent or superior to oseltamivir. The most active compound 31, a heptavalent oleanolic acid-beta-cyclodextrin conjugate, shows an up to 125-fold potency enhancement by its IC50 value over the corresponding monovalent conjugate and oleanolic acid, disclosing a clear multivalent effect. Further studies show that three compounds 31-33 exhibited broad spectrum inhibitory activity against other two human influenza A/JX/312 (H3N2) and A/HN/1222 (H3N2) viruses with the IC50 values at 2.47-14.90 MUM. Most importantly, we found that compound 31, one of the best representative conjugate, binds tightly to the viral envelope hemagglutinin with a dissociation constant of KD = 2.08 MUM, disrupting the interaction of hemagglutinin with the sialic acid receptor and thus the attachment of viruses to host cells. Our study might establish a strategy for the design of new pharmaceutical agents based on multivalency so as to block influenza virus entry into host cells. PMID- 26686048 TI - Fasting and 2-hour plasma glucose, and HbA1c in pregnancy and the postpartum risk of diabetes among Chinese women with gestational diabetes. AB - AIMS: Very few studies have assessed the association of fasting and 2h glucose, and HbA1c during pregnancy with postpartum diabetes risk among women with prior gestational diabetes mellitus (GDM). We assessed the association of fasting glucose, 2h glucose and HbA1c at 26-30 gestational weeks with postpartum diabetes risk among women with prior GDM. METHODS: A cohort study in 1263 GDM women at 1-5 years after delivery was performed. Cox proportional hazards regression models were used to evaluate the association of fasting and 2h plasma glucose, and HbA1c at 26-30 gestational weeks with the risk of diabetes at postpartum. RESULTS: The multivariable-adjusted (age, pre-pregnancy body mass index, weight gain during pregnancy, current body mass index, family history of diabetes, marital status, education, family income, smoking status, passive smoking, leisure-time physical activity, alcohol drinking, and intake of energy, saturated fat, and dietary fiber) hazard ratios of postpartum diabetes were 1.61 (95% confidence interval [CI]: 1.36-1.91) for each 1 mmol/l increase in fasting glucose during pregnancy, 1.63 (95% CI: 1.45-1.84) for each 1 mmol/l increase in 2h glucose during pregnancy, 2.11 (95% CI: 1.50-2.97) for each 1 unit (%) increase in HbA1c during pregnancy. When fasting glucose, 2h glucose and HbA1c during pregnancy were entered multivariable-adjusted model simultaneously, 2h glucose and HbA1c but not fasting glucose remained to be significant and positive predictors for postpartum diabetes. CONCLUSIONS: For women with prior GDM, 2h plasma glucose and HbA1c during pregnancy are independent predictors of postpartum diabetes, but fasting plasma glucose during pregnancy is not. PMID- 26686051 TI - The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing. AB - Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. PMID- 26686052 TI - Inhibition of autophagy overcomes the nanotoxicity elicited by cadmium-based quantum dots. AB - Cadmium-based quantum dots (QDs) have shown their values in disease diagnosis, cellular and molecular tracking, small-animal imaging, and therapeutic drug delivery. However, the potential safety problems of QDs, mainly due to their nanotoxicities by unclear mechanisms, have greatly limited its applications. To reverse this situation, we investigated the underlying biological mechanisms of the toxicity of Quantum Dots CdTe/CdS 655 (QDs 655) in this work. QDs 655 was found to elicit nanotoxicity in vitro and in vivo. During the process, autophagy was activated, which was characterized by three main stages of autophagic flux including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Furthermore, the autophagic cell death was demonstrated in vitro under QDs 655 treatment while inhibition of autophagy by pharmacological inhibitors or genetic approaches could attenuate the toxicity induced by QDs 655 in vitro and in vivo. These results indicated that autophagic flux and autophagic cell death were triggered by QDs 655, which elucidated the critical role of autophagy in QDs 655 induced toxicity. Our data may suggest the approach to overcome the toxicity of QDs and other nanoparticles by autophagy inhibition. PMID- 26686045 TI - Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study. AB - BACKGROUND: The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. METHODS: We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3-12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. FINDINGS: 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0.82, 95% CI 0.70 0.97; p=0.020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1.18, 0.99 1.40; p=0.056). Median follow-up for the mild disease cohort study was 2.24 years (IQR 2.22-2.85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0.98, 95% CI 0.86-1.11; p=0.82) or homozygous girls or hemizygous boys (0.93, 0.82-1.04; p=0.25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. INTERPRETATION: Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. FUNDING: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative). PMID- 26686053 TI - A Prospective Randomized Comparative Study of Cold Lateral Condensation Versus Core/Gutta-percha in Teeth with Periapical Lesions. AB - INTRODUCTION: The aim of this study was to compare the outcome of root canal treatment using either Thermafil (TF; Dentsply Maillefer, Ballaigues, Switzerland) or the cold lateral condensation (CLC) obturation technique in teeth with periapical lesions and to investigate the influence on postoperative pain and treatment outcomes. METHODS: After standardized root canal preparation technique, 112 teeth were obturated with either the TF or the CLC technique during 2 sessions by single operator. Postoperative pain, obturation length, and treatment outcomes were recorded. The teeth were reviewed clinically and radiographically for 2 years. RESULTS: Although there were no significant differences between the techniques in the incidence of postoperative pain at 24 hours (P > .05), the incidence of pain was significantly higher in the TF group than in the CLC group at 48 hours (P < .05). During the 2-year follow-up period, there was no statistically significant difference in the success rate of the teeth treated with TF (96.4%) in comparison with those treated with CLC (98.2%) (P > .05). CONCLUSIONS: In this study, the outcome of the root canal treatment of teeth using the TF and CLC techniques revealed that these techniques are useful for root canal obturation. PMID- 26686054 TI - Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex. AB - Cyclodextrins are cyclic oligosaccharides that have been recognized as pharmaceutical adjuvants for the past 20 years. The molecular structure of these glucose derivatives, which approximates a truncated cone, bucket, or torus, generates a hydrophilic exterior surface and a nonpolar interior cavity. Cyclodextrins can interact with appropriately sized drug molecules to yield an inclusion complex. These noncovalent inclusion complexes offer a variety of advantages over the noncomplexed form of a drug. Cyclodextrins are primarily used to enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Their other applications include preventing drug-drug interactions, converting liquid drugs into microcrystalline powders, minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell. Here, we discuss the physical chemical properties of various cyclodextrins, including the effects of substitutions on these properties. Additionally, we report on the regulatory status of their use, commercial products containing cyclodextrins, toxicological considerations, and the forces involved in complex formation. We also highlight the types of complex formed and discuss the methods used to determine the types of complex present. PMID- 26686056 TI - Interplay of metals and bromine with dioxin-related compounds concentrated in e waste open burning soil from Agbogbloshie in Accra, Ghana. AB - Open burning of electronic waste (e-waste) releases various metals and organohalogen compounds in the environment. Here we investigated the interplay of metals (Cu, Pb, Zn, Fe, Co, and Sr) and bromine (Br) in the formation of dioxin related compounds (DRCs), including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs), as well as non regulated DRCs such as polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and their monobrominated PCDD/Fs in soils sampled from open burning e-waste sites at Agbogbloshie in Accra, Ghana. The predominant DRCs were PBDFs, PCDFs, PCDDs, and DL-PCBs. Statistical analyzes, X-ray absorption spectroscopy, and the PCDF/PCDD ratio suggested possible formation paths of PCDD/Fs and DL-PCBs by catalytic behaviors of copper chlorides (CuCl, CuCl2, and Cu2(OH)3Cl) and thermal breakdown of polyvinyl chloride. Predominant formation of brominated furans may be derived from electron transfer from intermediates of PBDE to copper, Cu(II) -> Cu(I). Lead chloride also contributed to generate DRCs and may become highly bioaccessible through the open burning of e-waste. The main zinc species (ZnCl2 and ZnS) suggested a possible relationship to generate DRCs and specific zinc source such as tire burning. Cu, Pb, Zn, and Br contained in various e-wastes, wires/cables, plastics, and tires strongly influenced generation of many DRCs. PMID- 26686057 TI - Uptake and bioaccumulation of Cry toxins by an aphidophagous predator. AB - Uptake of Cry toxins by insect natural enemies has rarely been considered and bioaccumulation has not yet been demonstrated. Uptake can be demonstrated by the continued presence of Cry toxin after exposure has stopped and gut contents eliminated. Bioaccumulation can be demonstrated by showing uptake and that the concentration of Cry toxin in the natural enemy exceeds that in its food. We exposed larvae of the aphidophagous predator, Harmonia axyridis, to Cry1Ac and Cry1F through uniform and constant tritrophic exposure via an aphid, Myzus persicae, and looked for toxin presence in the pupae. We repeated the experiment using only Cry1F and tested newly emerged adults. Both Cry toxins were detected in pupae, and Cry1F was detected in recently emerged, unfed adults. Cry1Ac was present 2.05 times and Cry1F 3.09 times higher in predator pupae than in the aphid prey. Uptake and bioaccumulation in the third trophic level might increase the persistence of Cry toxins in the food web and mediate new exposure routes to natural enemies. PMID- 26686058 TI - Uptake, translocation and transformation of antimony in rice (Oryza sativa L.) seedlings. AB - Antimony (Sb), as a toxic metalloid, has been gaining increasing research concerns due mainly to its severe pollution in many places. Rice has been identified to be the dominant intake route of Sb by residents close to the Sb mining areas. A hydroponic experiment was conducted to investigate the difference in uptake, translocation and transformation of Sb in rice seedlings of four cultivars exposed to 0.2 or 1.0 mg/L of Sb(V). The results showed that mass concentration of iron plaque (mg/kg FW) formed at the root surfaces of cultivar N was the highest among all tested cultivars at both low and high exposure levels of Sb(V). The accumulated Sb concentration in iron plaque significantly increased with an increase in mass concentration of iron plaque formed at the rice root. The total amount of iron plaque (mg/pot) at rice root generally increased with increasing exposed Sb(V) concentration, which was closely associated with the increasing lipid peroxidation in roots. Concentration percentage of Sb in rice root significantly reduced as the corresponding value in the iron plaque increased, suggesting that iron plaque formation strongly suppressed uptake of Sb by rice root. Sb concentration in rice tissues followed an order: root > stem, leaf. The japonica rice (cultivars N and Z) exhibited a stronger translocation tendency of Sb from root to stem than indica hybrid rice (cultivars F and G). Translocation of Sb from root of cultivar F to its stem and leaf was sharply enhanced with increasing Sb exposure concentration. Sb(V) could be reduced to Sb(III) in rice tissues, especially in stems (10-26% of the total Sb). For the sake of food safety, the difference in uptake, translocation and transformation of Sb in rice species planted in Sb-contaminated soils should be taken into consideration. PMID- 26686059 TI - Concentrations, distribution, sources and risk assessment of organohalogenated contaminants in soils from Kenya, Eastern Africa. AB - The organohalogenated contaminants (OCs) including 12 organochlorine pesticides (OCPs), 7 indicator polychlorinated biphenyls (PCBs) and 7 polybrominated diphenyl ethers (PBDEs) were determined in soils collected from Kenya, Eastern Africa. The total OCPs fell in the range of n.d-49.74 MUg kg(-1) dry weight (dw), which was dominated by DDTs and endosulfan. Identification of pollution sources indicated new input of DDTs for malaria control in Kenya. The total PCBs ranged from n.d. to 55.49 MUg kg(-1) dw, dominated by penta- and hexa-PCBs, probably associated with the leakage of obsolete transformer oil. The soils were less contaminated by PBDEs, ranging from 0.19 to 35.64 MUg kg(-1) dw. The predominant PBDE congeners were penta-, tri- or tetra-BDEs, varying among different sampling sites. Risk assessment indicated potential human health risks posed by OCs in soils from Kenya, with PCBs as the most contributing pollutants. The local authorities are recommended to make best efforts on management of OC pollution, particularly from DDTs and PCBs to meet the requirement of Stockholm Convention. PMID- 26686061 TI - Building workforce capacity for ethical reflection in health promotion: a practitioner's experience. AB - Health promotion does not have a code of ethics, although attempts have been made to assist practitioners in their understanding and application of ethical concepts. This article describes and analyses one such attempt, sustained from 2006 to 2014 in rural South Australia. The attempt comprised capacity-building activities that were informed by principles of organisational change management, especially the principle of creating champions. The article also presents a framework (largely comprising ethical questions) that may help practitioners as a prompt and guide to ethical reflection. The framework was developed to be as accessible as possible in light of the diverse educational backgrounds found in rural settings. Finally, the article highlights some philosophical dimensions to the framework and defends its role, proposing that ethical reflection is integral to good practice and never simply the province of theorists. The article does all this with a view to stimulating discussion on how to increase the frequency and quality of ethical reflection undertaken by health promotion practitioners. PMID- 26686060 TI - Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases. AB - The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID- 26686055 TI - Peroxisomes in brain development and function. AB - Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer's disease, autism and amyotrophic lateral sclerosis. PMID- 26686062 TI - Negative Ulnar Variance and Kienbock Disease. AB - PURPOSE: To test the primary null hypothesis that there is no difference in mean ulnar variance (UV) scaled to the length of the capitates between 166 wrists with Kienbock disease and an equal number of matched controls and to test the secondary null hypothesis that mean scaled UV does not vary based on age, sex, or race in both Kienbock and control wrists. METHODS: Ulnar variance was measured on posteroanterior radiographs of the wrist as the distance between a line through the midpoint between the volar and the dorsal edges of the ulnar margin of the radius and a line tangential to the most distal aspect of the carpal surface of the head of the ulna, both perpendicular to the longitudinal axis of the radius. Measurement of UV was scaled to the length of the capitate, resulting in a UV to capitate height (UV:CH) ratio. RESULTS: We found a significant difference in mean UV:CH ratio between patients with Kienbock disease and a control group matched by age, sex, race, and limb. The prevalence of negative UV was high in both patients with Kienbock disease and matched controls. There were no differences in mean UV:CH ratio with respect to age, sex, or race among patients with Kienbock disease or matched controls. CONCLUSIONS: The precise role of ulna minus in the development of Kienbock disease remains uncertain and unanswered, given that many patients with Kienbock disease have neutral or positive UV. In addition, a large proportion of the normal population has negative UV, whereas Kienbock disease is rare. PMID- 26686063 TI - Variables Prognostic for Delayed Union and Nonunion Following Ulnar Shortening Fixed With a Dedicated Osteotomy Plate. AB - PURPOSE: To examine potential risk factors for the development of delayed or nonunion following elective ulnar shortening osteotomy using a dedicated osteotomy plating system. METHODS: We performed a retrospective review of all patients who underwent elective ulnar shortening using the TriMed single osteotomy dynamic compression plating system by 1 of 2 fellowship-trained hand surgeons over a 5-year period. Demographic data and medical, surgical, and social histories were reviewed. Time to bony union was determined radiographically by a blinded reviewer. Bivariate statistical analysis was performed to examine the effect of explanatory variables on the time to union and the incidence of delayed or nonunion. Those variables associated with the development of delayed or nonunion were used in a multivariate logistic regression model. Complications, including the need for additional surgery, were also recorded. RESULTS: Seventy two ulnar shortening osteotomy procedures were performed in 69 patients. Delayed union, defined as >= 6 months to union, occurred in 8 of 72 cases (11%). Of 72 surgeries, 4 (6%) resulted in nonunions, all of which required additional surgery. Hardware removal was performed in 13 of 72 (18%) of the cases. Time to union was significantly increased in smokers (6 +/- 3 months) versus nonsmokers (3 +/- 1 months). On multivariable analysis, diabetics and active smokers demonstrated a significantly higher risk of developing delayed union or nonunion. Patient age, sex, body mass index, thyroid disease, worker's compensation status, alcohol use, and amount smoked daily did not have an effect on the time to union or the incidence of delayed or nonunion. CONCLUSIONS: Despite the use of an osteotomy-specific plating system, smokers and diabetics were at significantly higher risk for both delayed union and nonunion following elective ulnar shortening osteotomy. Other known risk factors for suboptimal bony healing were not found to have a deleterious effect. PMID- 26686064 TI - Vandetanib as a potential new treatment for estrogen receptor-negative breast cancers. AB - The receptor tyrosine kinase RET is implicated in the progression of luminal breast cancers (BC) but its role in estrogen receptor (ER) negative tumors is unknown. Here we investigated the expression of RET in breast cancer patients tumors and patient-derived xenografts (PDX) and evaluated the therapeutic potential of Vandetanib, a tyrosin kinase inhibitor with strong activity against RET, EGFR and VEGFR2, in ER negative breast cancer PDX. The RT-PCR analysis of RET expression in breast tumors of 446 patients and 57 PDX, showed elevated levels of RET in ER+ and HER2+ subtypes and in a small subgroup of triple negative breast cancers (TNBC). The activity of Vandetanib was tested in vivo in three PDX models of TNBC and one model of HER2+ BC with different expression levels of RET and EGFR. Vandetanib induced tumor regression in PDX models with high expression of RET or EGFR. The effect was associated with inhibition of RET/EGFR phosphorylation and MAP kinase pathway and increased necrosis. In a PDX model with no expression of RET nor EGFR, Vandetanib slowed tumor growth without inducing tumor regression. In addition, treatment by Vandetanib decreased expression of murine Vegf receptors and the endothelial marker Cd31 in the four PDX models tested, suggesting inhibition of tumor vascularization. In summary, these preclinical results suggest that Vandetanib treatment could be useful for patients with ER negative breast cancers overexpressing Vandetanib's main targets. PMID- 26686065 TI - BPA exposure during in vitro oocyte maturation results in dose-dependent alterations to embryo development rates, apoptosis rate, sex ratio and gene expression. AB - Alterations in the oocyte's environment can negatively affect embryo development. Oocyte quality, which can determine embryonic viability, is easily perturbed, thus factors affecting normal oocyte maturation are a concern. Bisphenol A (BPA) is an endocrine disrupting chemical that elicits a variety of reproductive effects. BPA has previously been found to disrupt meiosis, however the embryonic effects in mammals are not well documented. Here, bovine oocytes were matured in vitro with and without BPA treatment. Resulting embryos exhibited decreased embryonic development rates, increased apoptosis, and a skewed sex ratio. Gene expression in blastocysts was not altered, whereas treatment with 15ng/mL BPA resulted in increased expression of several of the genes studies, however this increase was largely due to a vehicle effect. BPA exposure during oocyte maturation in vitro can therefore, in a dose-dependent way, decrease oocyte and embryo quality and developmental potential and affect gene expression of developmentally important transcripts. PMID- 26686066 TI - Ammonium and potassium removal from swine liquid manure using clinoptilolite, chabazite and faujasite zeolites. AB - This study concerns cationic exchanges performed in order to remove ammonium and potassium cations from manure by using various zeolites: clinoptilolite, chabazite and NaX faujasite. First, the effect of temperature (25 degrees C and 40 degrees C) on the exchange rate between zeolites and an ammonium chloride solution was investigated. Then, cationic exchanges were performed on these three zeolites using on one side a mixed ammonium and potassium chloride solution reproducing the chemical composition of a swine manure and on the other side the corresponding liquid manure. No significant difference was observed on the exchange rate and the trapping of ammonium cations by changing the temperature (25 or 40 degrees C). Clinoptilolite showed a good selectivity towards ammonium cations using model (NH4Cl, and mixed NH4Cl/KCl) solutions but is less efficient with the liquid manure. Chabazite and faujasite were found more efficient than clinoptilolite for trapping ammonium cations. However, NaX faujasite enables trapping 3 times more ammonium cations than chabazite from manure (60 and 20 mg/g, respectively). Moreover, chabazite allowed to trap the same amount of potassium cations than NaX faujasite (33 and 35 mg/g, respectively). PMID- 26686067 TI - Phytotoxicity as an indicator of stability of broiler production residues. AB - Beddings used for successive broiler lots act as substrate to absorb water and feed from the excreta and may be subsequently used as agricultural fertilizers. This study evaluated the physicochemical characteristics and the phytotoxicity of beddings used to raise five consecutive broiler lots in five aviaries. Samples were collected for beddings not used yet and for beddings used at each of the five broiler lots. Lettuce and cucumber seeds were considered as phytotoxicity bioindicators. As beddings were used for greater number of lots, N, Ca, K, Mg and P contents generally increased, but the C content decreased, the pH alkalinized and humidity was reduced (P < 0.05). The germination index for lettuce and cucumber seeds was reduced with increased bedding (P < 0.05). Beddings used for at least five broiler lots presented decreased C:N ratio and would not recommended for agricultural use due to its toxicity for both tested seeds. PMID- 26686068 TI - Efficiency assessment of wastewater treatment plants: A data envelopment analysis approach integrating technical, economic, and environmental issues. AB - The assessment of the efficiency of wastewater treatment plants (WWTPs) is essential to compare their performance and consequently to identify the best operational practices that can contribute to the reduction of operational costs. Previous studies have evaluated the efficiency of WWTPs using conventional data envelopment analysis (DEA) models. Most of these studies have considered the operational costs of the WWTPs as inputs, while the pollutants removed from wastewater are treated as outputs. However, they have ignored the fact that each pollutant removed by a WWTP involves a different environmental impact. To overcome this limitation, this paper evaluates for the first time the efficiency of a sample of WWTPs by applying the weighted slacks-based measure model. It is a non-radial DEA model which allows assigning weights to the inputs and outputs according their importance. Thus, the assessment carried out integrates environmental issues with the traditional "techno-economic" efficiency assessment of WWTPs. Moreover, the potential economic savings for each cost item have been quantified at a plant level. It is illustrated that the WWTPs analyzed have significant room to save staff and energy costs. Several managerial implications to help WWTPs' operators make informed decisions were drawn from the methodology and empirical application carried out. PMID- 26686069 TI - Phosphate adsorption from wastewater using zirconium (IV) hydroxide: Kinetics, thermodynamics and membrane filtration adsorption hybrid system studies. AB - Excessive phosphate in wastewater should be removed to control eutrophication of water bodies. The potential of employing amorphous zirconium (Zr) hydroxide to remove phosphate from synthetic wastewater was studied in batch adsorption experiments and in a submerged membrane filtration adsorption hybrid (MFAH) reactor. The adsorption data satisfactorily fitted to Langmuir, pseudo-first order and pseudo-second order models. Langmuir adsorption maxima at 22 degrees C and pHs of 4.0, 7.1, and 10.0 were 30.40, 18.50, and 19.60 mg P/g, respectively. At pH 7.1 and temperatures of 40 degrees C and 60 degrees C, they were 43.80 and 54.60 mg P/g, respectively. The thermodynamic parameters, DeltaG degrees and DeltaS degrees were negative and DeltaH degrees was positive. FTIR, zeta potential and competitive phosphate, sulphate and nitrate adsorption data showed that the mechanism of phosphate adsorption was inner-sphere complexation. In the submerged MFAH reactor experiment, when Zr hydroxide was added at doses of 1-5 g/L once only at the start of the experiment, the removal of phosphate from 3 L of wastewater containing 10 mg P/L declined after 5 h of operation. However, when Zr hydroxide was repeatedly added at 5 g/L dose every 24 h, satisfactory removal of phosphate was maintained for 3 days. PMID- 26686070 TI - Four decades of land-cover, land-use and hydroclimatology changes in the Itacaiunas River watershed, southeastern Amazon. AB - Long-term human-induced impacts have significantly changed the Amazonian landscape. The most dramatic land cover and land use (LCLU) changes began in the early 1970s with the establishment of the Trans-Amazon Highway and large government projects associated with the expansion of agricultural settlement and cattle ranching, which cleared significant tropical forest cover in the areas of new and accelerated human development. Taking the changes in the LCLU over the past four decades as a basis, this study aims to determine the consequences of land cover (forest and savanna) and land use (pasturelands, mining and urban) changes on the hydroclimatology of the Itacaiunas River watershed area of the located in the southeastern Amazon region. We analyzed a multi-decadal Landsat dataset from 1973, 1984, 1994, 2004 and 2013 and a 40-yr time series of water discharge from the Itacaiunas River, as well as air temperature and relative humidity data over this drainage area for the same period. We employed standard Landsat image processing techniques in conjunction with a geographic object-based image analysis and multi-resolution classification approach. With the goal of detecting possible long-term trends, non-parametric Mann-Kendall test was applied, based on a Sen slope estimator on a 40-yr annual PREC, TMED and RH time series, considering the spatial average of the entire watershed. In the 1970s, the region was entirely covered by forest (99%) and savanna (~0.3%). Four decades later, only ~48% of the tropical forest remains, while pasturelands occupy approximately 50% of the watershed area. Moreover, in protected areas, nearly 97% of the tropical forest remains conserved, while the forest cover of non-protected areas is quite fragmented and, consequently, unevenly distributed, covering an area of only 30%. Based on observational data analysis, there is evidence that the conversion of forest cover to extensive and homogeneous pasturelands was accompanied by systematic modifications to the hydroclimatology cycle of the Itacaiunas watershed, thus highlighting drier environmental conditions due to a rise in the region's air temperature, a decrease in the relative humidity, and an increase in river discharge. PMID- 26686071 TI - CO2 sequestration through aqueous accelerated carbonation of BOF slag: A factorial study of parameters effects. AB - A factorial study was conducted on basic oxygen furnace slag from a steelmaking industry with the aim of systematically identifying the individual and joint effects of the operating parameters (total pressure, CO2 concentration in the gas phase and temperature) on the CO2 sequestration yield of a direct aqueous carbonation process. Each operating parameter was varied over a range of three levels according to a 3(3) factorial design, resulting in 27 carbonation experiments. The carbonation performance and the changes in particle size and mineralogical characteristics of the slag were investigated in detail. The analysis of the experimental results indicated large effects of the operating factors on CO2 uptake, which was observed to span the range 6.7-53.6 g CO2/100 g slag. The best carbonation performance achieved was particularly significant compared to previous studies, even more considering the relative mild operating conditions adopted (P = 5 bar, C = 40% vol. CO2, T = 50 degrees C, t = 4 h). The analysis of the solid and liquid phases at the end of the carbonation treatment evidenced significant changes in the physical, chemical and mineralogical composition of the material. In particular, evidence was gained of other elements (Mg, Fe, Mn, Zn) in addition to Ca being intensively involved in the carbonation reactions, with a variety of carbonate phases being produced in addition to calcium carbonate forms. PMID- 26686072 TI - Lab-scale investigation on remediation of diesel-contaminated aquifer using microwave energy. AB - Aquifer contamination with diesel fuel is a worldwide environmental problem, and related available remediation technologies may not be adequately efficient, especially for the simultaneous treatment of both solid and water phases. In this paper, a lab-scale 2.45 GHz microwave (MW) treatment of an artificially diesel contaminated aquifer was applied to investigate the effects of operating power (160, 350 and 500 W) and time on temperature profiles and contaminant removal from both solid and water phases. Results suggest that in diesel-contaminated aquifer MW remediation, power significantly influences the final reachable temperature and, consequently, contaminant removal kinetics. A maximum temperature of about 120 degrees C was reached at 500 W. Observed temperature values depended on the simultaneous irradiation of both aquifer grains and groundwater. In this case, solid phase heating is limited by the maximum temperature that interstitial water can reach before evaporation. A minimal residual diesel concentration of about 100 mg kg(-1) or 100 mg L(-1) was achieved by applying a power of 500 W for a time of 60 min for the solid or water phase, respectively. Measured residual TPH fractions showed that MW heating resulted in preferential effects of the removal of different TPH molecular weight fractions and that the evaporation-stripping phenomena plays a major role in final contaminant removal processes. The power low kinetic equation shows an excellent fit (r(2) > 0.993) with the solid phase residual concentration observed for all the powers investigated. A maximum diesel removal of 88 or 80% was observed for the MW treatment of the solid or water phase, respectively, highlighting the possibility to successfully and simultaneously remediate both the aquifer phases. Consequently, MW, compared to other biological or chemical-physical treatments, appears to be a better choice for the fast remediation of diesel-contaminated aquifers. PMID- 26686073 TI - Removal of Mefenamic acid from aqueous solutions by oxidative process: Optimization through experimental design and HPLC/UV analysis. AB - Mefenamic acid (MEF) is a non-steroidal anti-inflammatory drug indicated for relief of mild to moderate pain, and for the treatment of primary dysmenorrhea. The presence of MEF in raw and sewage waters has been detected worldwide at concentrations exceeding the predicted no-effect concentration. In this study, using experimental designs, different oxidative processes (H2O2, H2O2/UV, fenton and Photo-fenton) were simultaneously evaluated for MEF degradation efficiency. The influence and interaction effects of the most important variables in the oxidative process (concentration and addition mode of hydrogen peroxide, concentration and type of catalyst, pH, reaction period and presence/absence of light) were investigated. The parameters were determined based on the maximum efficiency to save time and minimize the consumption of reagents. According to the results, the photo-Fenton process is the best procedure to remove the drug from water. A reaction mixture containing 1.005 mmol L(-1) of ferrioxalate and 17.5 mmol L(-1) of hydrogen peroxide, added at the initial reaction period, pH of 6.1 and 60 min of degradation indicated the most efficient degradation, promoting 95% of MEF removal. The development and validation of a rapid and efficient qualitative and quantitative HPLC/UV methodology for detecting this pollutant in aqueous solution is also reported. The method can be applied in water quality control that is generated and/or treated in municipal or industrial wastewater treatment plants. PMID- 26686074 TI - A review on the role of organic inputs in maintaining the soil carbon pool of the terrestrial ecosystem. AB - Among the numerous sources of greenhouse gases, emissions of CO2 are considerably affected by changes in the extent and type of land use, e.g., intensive agriculture, deforestation, urbanization, soil erosion, or wetland drainage. As a feasible option to control emissions from the terrestrial ecosystems, the scientific community has explored the possibility of enhancing soil carbon (C) storage capacity. Thus, restoration of damaged lands through conservation tillage, crop rotation, cover cropping, reforestation, sub-soiling of compacted lands, sustainable water management practices, and organic manuring are the major antidotes against attenuation of soil organic C (SOC) stocks. In this research, we focused on the effect of various man-made activities on soil biotic organics (e.g., green-, farm-yard manure, and composts) to understand how C fluxes from various sources contribute to the establishment of a new equilibrium in the terrestrial ecosystems. Although such inputs substitute a portion of chemical fertilizers, they all undergo activities that augment the rate and extent of decay to deplete the SOC bank. Here, we provide perspectives on the balancing factors that control the mineralization rate of organic matter. Our arguments are placed in the background of different land use types and their impacts on forests, agriculture, urbanization, soil erosion, and wetland destruction. PMID- 26686075 TI - Decontamination of heavy metal laden sewage sludge with simultaneous solids reduction using thermophilic sulfur and ferrous oxidizing species. AB - A possibility of using simultaneous sewage sludge digestion and metal leaching (SSDML) process at the thermophilic temperature to remove heavy metals and suspended solids from sewage sludge is explored in this study. Though thermophilic sludge digestion efficiently produces a stable sludge, its inability to remove heavy metals requires it to be used in tandem with another process like bioleaching for metal reduction. Previously, different temperature optima were known for the heterotrophs (thermophilic) responsible for the sludge digestion and the autotrophs involved in bioleaching (mesophilic), because of which the metal concentration was brought down separately in a different reactor. In our study, SSDML process was carried out at 50 degrees C (thermophilic) by using ferrous sulfate (batch-1) and sulfur (batch-2) as the energy source in two reactors. The concentration of volatile suspended solids reduced by >40% in both batches, while that of heavy metals zinc, copper, chromium, cadmium and nickel decreased by >50% in both batch-1 and batch-2. Lead got leached out only in batch 1. Using 16S rRNA gene-based PCR-denaturing gradient gel electrophoresis analysis, Alicyclobacillus tolerans was found to be the microorganism responsible for lowering the pH in both the reactors at thermophilic temperature. The indicator organism count was also below the maximum permissible limit making sludge suitable for agricultural use. Our results indicate that SSDML at thermophilic temperature can be effectively used for reduction of heavy metals and suspended solids from sewage sludge. PMID- 26686076 TI - Defining a quantitative framework for evaluation and optimisation of the environmental impacts of mega-event projects. AB - This paper presents a novel quantitative methodology for the evaluation and optimisation of the environmental impacts of the whole life cycle of a mega-event project: construction and staging the event and post-event site redevelopment and operation. Within the proposed framework, a mathematical model has been developed that takes into account greenhouse gas (GHG) emissions resulting from use of transportation fuel, energy, water and construction materials used at all stages of the mega-event project. The model is applied to a case study - the London Olympic Park. Three potential post-event site design scenarios of the Park have been developed: Business as Usual (BAU), Commercial World (CW) and High Rise High Density (HRHD). A quantitative summary of results demonstrates that the highest GHG emissions associated with the actual event are almost negligible compared to those associated with the legacy phase. The highest share of emissions in the legacy phase is attributed to embodied emissions from construction materials (almost 50% for the BAU and HRHD scenarios) and emissions resulting from the transportation of residents, visitors and employees to/from the site (almost 60% for the CW scenario). The BAU scenario is the one with the lowest GHG emissions compared to the other scenarios. The results also demonstrate how post-event site design scenarios can be optimised to minimise the GHG emissions. The overall outcomes illustrate how the proposed framework can be used to support decision making process for mega-event projects planning. PMID- 26686077 TI - Heterogeneous photocatalytic degradation of the endocrine-disrupting chemical Benzophenone-3: Parameters optimization and by-products identification. AB - Benzophenone-3 (BP3) is one of the most used UV filters. Its disruptive effect on the endocrine system of different living beings has been demonstrated by several research groups. Present work addresses on a photocatalytic degradation of BP3 using particles of titanium dioxide in aqueous solutions considering the effect of operating parameters such as pH, catalyst and pollutant initial concentrations, and the presence of hydrogen peroxide, acetonitrile and isopropanol in the solution. In this way, a face centered, central composite design was carried out for the identification of significant factors or interactions that allow the determination of the conditions under which the pollutant suffers the highest rates of degradation. A solution initial pH of 9.0, a TiO2 concentration of 1.184 g L(-1) and an H2O2 concentration of 128.069 mg L( 1) were established as the optimal conditions for the substrate removal. In aqueous solutions and low concentrations of the pollutant (<2 mg L(-1)) photocatalytic degradation followed a pseudo-first order kinetics. After 300 min of treatment, ~67% of the dissolved organic carbon was removed, which together with a reduction in toxicity and an increase in biodegradability confirmed that photocatalysis with TiO2 is a potential method to remove BP3 from water. Additionally, tests using acetonitrile as solvent and isopropanol as hydroxyl radical (OH(.)) scavenger suggested that, OH(.) was the main agent responsible of substrate degradation. Finally, ten process by-products were identified and a degradation route was proposed. PMID- 26686079 TI - Non-viral gene therapy: Gains and challenges of non-invasive administration methods. AB - Gene therapy is becoming an influential part of the rapidly increasing armamentarium of biopharmaceuticals for improving health and combating diseases. Currently, three gene therapy treatments are approved by regulatory agencies. While these treatments utilize viral vectors, non-viral alternative technologies are also being developed to improve the safety profile and manufacturability of gene carrier formulations. We present an overview of gene-based therapies focusing on non-viral gene delivery systems and the genetic therapeutic tools that will further revolutionize medical treatment with primary focus on the range and development of non-invasive delivery systems for dermal, transdermal, ocular and pulmonary administrations and perspectives on other administration methods such as intranasal, oral, buccal, vaginal, rectal and otic delivery. PMID- 26686080 TI - Characterization of pore structure of polymer blended films used for controlled drug release. AB - The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross-sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead characterizing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies. PMID- 26686078 TI - Targeting specific cells in the brain with nanomedicines for CNS therapies. AB - Treatment of Central Nervous System (CNS) disorders still remains a major clinical challenge. The Blood-Brain Barrier (BBB), known as the major hindrance, greatly limits therapeutics penetration into the brain. Moreover, even though some therapeutics can cross BBB based on their intrinsic properties or via the use of proper nanoscale delivery vehicles, their therapeutic efficacy is still often limited without the specific uptake of drugs by the cancer or disease associated cells. As more studies have started to elucidate the pathological roles of major cells in the CNS (for example, microglia, neurons, and astrocytes) for different disorders, nanomedicines that can enable targeting of specific cells in these diseases may provide great potential to boost efficacy. In this review, we aim to briefly cover the pathological roles of endothelial cells, microglia, tumor-associated microglia/macrophage, neurons, astrocytes, and glioma in CNS disorders and to highlight the recent advances in nanomedicines that can target specific disease-associated cells. Furthermore, we summarized some strategies employed in nanomedicine to achieve specific cell targeting or to enhance the drug neuroprotective effects in the CNS. The specific targeting at the cellular level by nanotherapy can be a more precise and effective means not only to enhance the drug availability but also to reduce side effects. PMID- 26686081 TI - Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects. AB - The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases. PMID- 26686082 TI - Drug delivery to macrophages: Challenges and opportunities. AB - Macrophages are prevalent in the body and have roles in almost every aspect of human biology. They have often been considered a subject to avoid during drug delivery. However, with recent understanding of their diverse functions in diseases, macrophages have gained increasing interest as important therapeutic targets. To develop drug carriers to macrophages, it is important to understand their biological roles and requirements for efficient targeting. This review provides an overview of representative carriers and various approaches to address challenges in drug delivery to macrophages such as biodistribution, cellular uptake, intracellular trafficking, and drug release. PMID- 26686083 TI - SPON2, a newly identified target gene of MACC1, drives colorectal cancer metastasis in mice and is prognostic for colorectal cancer patient survival. AB - MACC1 (metastasis associated in colon cancer 1) is a prognostic biomarker for tumor progression, metastasis and survival of a variety of solid cancers including colorectal cancer (CRC). Here we aimed to identify the MACC1-induced transcriptome and key players mediating the MACC1-induced effects in CRC. We performed microarray analyses using CRC cells ectopically overexpressing MACC1. We identified more than 1300 genes at least twofold differentially expressed, including the gene SPON2 (Spondin 2) as 90-fold upregulated transcriptional target of MACC1. MACC1-dependent SPON2 expression regulation was validated on mRNA and protein levels in MACC1 high (endogenously or ectopically) and low (endogenously or by knockdown) expressing cells. Chromatin immunoprecipitation analysis demonstrated the binding of MACC1 to the gene promoter of SPON2. In cell culture, ectopic SPON2 overexpression induced cell viability, migration, invasion and colony formation in endogenously MACC1 and SPON2 low expressing cells, whereas SPON2 knockdown reduced proliferative, migratory and invasive abilities in CRC cells with high endogenous MACC1 and SPON2 expression. In intrasplenically transplanted NOD/SCID mice, metastasis induction was analyzed with control or SPON2-overexpressing CRC cells. Tumors with SPON2 overexpression induced liver metastasis (vs control animals without any metastases, P=0.0036). In CRC patients, SPON2 expression was determined in primary tumors (stages I-III), and survival time was analyzed by Kaplan-Meier method. CRC patients with high SPON2 expressing primary tumors demonstrated 8 months shorter metastasis-free survival (MFS) compared with patients with low SPON2 levels (P=0.053). Combining high levels of SPON2 and MACC1 improved the identification of high-risk patients with a 20-month shorter MFS vs patients with low biomarker expression. In summary, SPON2 is a transcriptional target of the metastasis gene MACC1. SPON2 induces cell motility in vitro and CRC metastasis in mice. In patients, SPON2 serves as prognostic indicator for CRC metastasis and survival, and might represent a promising target for therapeutic approaches. PMID- 26686084 TI - Regulation of breast tumorigenesis through acid sensors. AB - The low extracellular pH in the microenvironment has been shown to promote tumor growth and metastasis; however, the underlying mechanism is poorly understood. Particularly, little is known how the tumor cell senses the acidic signal to activate the acidosis-mediated signaling. In this study, we show that breast cancer cells express acid-sensing ion channel 1 (ASIC1), a proton-gated cation channel primarily expressed in the nervous system. RNA interference, knockout and rescue experiments demonstrate a critical role for ASIC1 in acidosis-induced reactive oxidative species and NF-kappaB activation, two key events for tumorigenesis. Mechanistically, ASIC1 is required for acidosis-mediated signaling through calcium influx. We show that as a cytoplasmic membrane protein, ASIC1 is also associated with mitochondria, suggesting that ASIC1 may regulate mitochondrial calcium influx. Importantly, interrogation of the Cancer Genome Atlas breast invasive carcinoma data set indicates that alterations of ASIC1 alone or combined with other 4 ASIC genes are significantly correlated with poor patient survival. Furthermore, ASIC1 inhibitors cause a significant reduction of tumor growth and tumor load. Together, these results suggest that ASIC1 contributes to breast cancer pathogenesis in response to acidic tumor microenvironments, and ASIC1 may serve as a prognostic marker and a therapeutic target for breast cancer. PMID- 26686085 TI - Tumor-suppressor NFkappaB2 p100 interacts with ERK2 and stabilizes PTEN mRNA via inhibition of miR-494. AB - Emerging evidence from The Cancer Genome Atlas has revealed that nuclear factor kappaB2 (nfkappab2) gene encoding p100 is genetically deleted or mutated in human cancers, implicating NFkappaB2 as a potential tumor suppressor. However, the molecular mechanism underlying the antitumorigenic action of p100 remains poorly understood. Here we report that p100 inhibits cancer cell anchorage-independent growth, a hallmark of cellular malignancy, by stabilizing the tumor-suppressor phosphatase and tensin homolog (PTEN) mRNA via a mechanism that is independent of p100's inhibitory role in NFkappaB activation. We further demonstrate that the regulatory effect of p100 on PTEN expression is mediated by its downregulation of miR-494 as a result of the inactivation of extracellular signal-regulated kinase 2 (ERK2), in turn leading to inhibition of c-Jun/activator protein-1-dependent transcriptional activity. Furthermore, we identify that p100 specifically interacts with non-phosphorylated ERK2 and prevents ERK2 phosphorylation and nuclear translocation. Moreover, the death domain at C-terminal of p100 is identified as being crucial and sufficient for its interaction with ERK2. Taken together, our findings provide novel mechanistic insights into the understanding of the tumor-suppressive role for NFkappaB2 p100. PMID- 26686086 TI - Tumor suppressor control of the cancer stem cell niche. AB - Mammary stem cells (MSCs) expansion is associated with aggressive human breast cancer. The nuclear receptor peroxisome proliferator activated receptor gamma (PPARgamma) is a breast cancer tumor suppressor, but the mechanisms of this suppression are not completely characterized. To determine whether PPARgamma regulates MSC expansion in mammary cancer, we deleted PPARgamma expression in the mammary epithelium of an in vivo model of basal breast cancer. Loss of PPARgamma expression reduced tumor latency, and expanded the CD24+/CD49f(hi) MSC population. PPARgamma-null mammary tumors exhibited increased angiogenesis, which was detected in human breast cancer. In vivo inhibition of a PPARgamma-regulated miR-15a/angiopoietin-1 pathway blocked increased angiogenesis and MSC expansion. PPARgamma bound and activated a canonical response element in the miR-15a gene. PPARgamma-null tumors were sensitive to the targeted anti-angiogenic drug sunitinib but resistant to cytotoxic chemotherapy. Normalization of tumor vasculature with sunitinib resulted in objective response to cytotoxic chemotherapy. Chemotherapy-treated PPARgamma-null mammary tumors exhibited luminal phenotype and expansion of unipotent CD61+ luminal progenitor cells. Transplantation of chemotherapy-treated luminal progenitor cells recapitulated the luminal phenotype. These results have important implications for anti angiogenic therapy in breast cancer patients. PMID- 26686087 TI - HER2 induced EMT and tumorigenicity in breast epithelial progenitor cells is inhibited by coexpression of EGFR. AB - The members of the epidermal growth factor receptor (EGFR) kinase family are important players in breast morphogenesis and cancer. EGFR2/HER2 and EGFR expression have a prognostic value in certain subtypes of breast cancer such as HER2-amplified, basal-like and luminal type B. Many clinically approved small molecular inhibitors and monoclonal antibodies have been designed to target HER2, EGFR or both. There is, however, still limited knowledge on how the two receptors are expressed in normal breast epithelium, what effects they have on cellular differentiation and how they participate in neoplastic transformation. D492 is a breast epithelial cell line with stem cell properties that can undergo epithelial to mesenchyme transition (EMT), generate luminal- and myoepithelial cells and form complex branching structures in three-dimensional (3D) culture. Here, we show that overexpression of HER2 in D492 (D492(HER2)) resulted in EMT, loss of contact growth inhibition and increased oncogenic potential in vivo. HER2 overexpression, furthermore, inhibited endogenous EGFR expression. Re-introducing EGFR in D492(HER2) (D492(HER2/EGFR)) partially reversed the mesenchymal state of the cells, as an epithelial phenotype reappeared both in 3D cultures and in vivo. The D492(HER2/EGFR) xenografts grow slower than the D492(HER2) tumors, while overexpression of EGFR alone (D492(EGFR)) was not oncogenic in vivo. Consistent with the EGFR-mediated epithelial phenotype, overexpression of EGFR drove the cells toward a myoepithelial phenotype in 3D culture. The effect of two clinically approved anti-HER2 and EGFR therapies, trastuzumab and cetuximab, was tested alone and in combination on D492(HER2) xenografts. While trastuzumab had a growth inhibitory effect compared with untreated control, the effect of cetuximab was limited. When administered in combination, the growth inhibitory effect of trastuzumab was less pronounced. Collectively, our data indicate that in HER2 overexpressing D492 cells, EGFR can behave as a tumor suppressor, by pushing the cells towards epithelial differentiation. PMID- 26686088 TI - Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system. AB - Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-beta1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-beta1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer. PMID- 26686089 TI - TBX2 represses PTEN in rhabdomyosarcoma and skeletal muscle. AB - Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children that shares many features of developing skeletal muscle. TBX2, a T-box family member, is highly upregulated in tumor cells of both major RMS subtypes where it functions as an oncogene. TBX2 is a repressor that is often overexpressed in cancer cells and functions in bypassing cell growth control, including the repression of the cell cycle regulators p14 and p21. We have found that TBX2 directly represses the tumor-suppressor phosphatase and tensin homolog (PTEN) in both RMS and normal muscle. Exogenous expression of TBX2 in normal muscle cells downregulates PTEN, and depletion or interference with TBX2 in RMS cells upregulates PTEN. Human RMS tumors show high levels of TBX2 and correspondingly low levels of PTEN. The expression of PTEN in clinical RMS samples is relatively uncharacterized, and we establish that suppression of PTEN is a frequent event in both subtypes of RMS. TBX2 represses PTEN by directly binding to the promoter and recruiting the histone deacetylase, HDAC1. RMS cells have high levels of activated AKT owing to the deregulation of phosphoinositide-3 kinase (PI3K) signaling, and depletion or interference with TBX2, which upregulates PTEN, results in a reduction of phospho-AKT. We have also found that the highly related T-box family member TBX3 does not repress PTEN in the muscle lineage. This work suggests that TBX2 is a central component of the PTEN/PI3K/AKT signaling pathway deregulation in RMS cells and that targeting TBX2 in RMS tumors may offer a novel therapeutic approach for RMS. PMID- 26686090 TI - FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2. AB - T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1 complex is thought to have a pivotal role in the transformation of thymocytes and is associated with a differentiation block and self-renewal. The transcription factor Forkhead Box P3 (FOXP3) was recently described to be expressed in a variety of malignancies including T-ALL. Here we show that increased FOXP3 levels negatively correlate with expression of genes regulated by the oncogenic TAL1 complex in human T-ALL patient samples as well as a T-ALL cell line ectopically expressing FOXP3. In these cells, FOXP3 expression results in altered regulation of cell cycle progression and reduced cell viability. Finally, we demonstrate that FOXP3 binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1, providing a molecular mechanism for FOXP3-mediated transcriptional modulation in T-ALL. Collectively, our findings provide initial evidence for a novel role of FOXP3 as a tumor suppressor in T-ALL through modulation of TAL1 transcriptional activity. PMID- 26686091 TI - A new ER-specific photosensitizer unravels (1)O2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT. AB - Photosensitizers (PS) are ideally devoid of any activity in the absence of photoactivation, and rely on molecular oxygen for the formation of singlet oxygen ((1)O2) to produce cellular damage. Off-targets and tumor hypoxia therefore represent obstacles for the use of PS for cancer photodynamic therapy. Herein, we describe the characterization of OR141, a benzophenazine compound identified through a phenotypic screening for its capacity to be strictly activated by light and to kill a large variety of tumor cells under both normoxia and hypoxia. This new class of PS unraveled an unsuspected common mechanism of action for PS that involves the combined inhibition of the mammalian target of rapamycin (mTOR) signaling pathway and proteasomal deubiquitinases (DUBs) USP14 and UCH37. Oxidation of mTOR and other endoplasmic reticulum (ER)-associated proteins drives the early formation of high molecular weight (MW) complexes of multimeric proteins, the concomitant blockade of DUBs preventing their degradation and precipitating cell death. Furthermore, we validated the antitumor effects of OR141 in vivo and documented its highly selective accumulation in the ER, further increasing the ER stress resulting from (1)O2 generation upon light activation. PMID- 26686093 TI - Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers. AB - Arginylation is an emerging post-translational modification mediated by arginyltransferase (ATE1) that is essential for mammalian embryogenesis and regulation of the cytoskeleton. Here, we discovered that Ate1-knockout (KO) embryonic fibroblasts exhibit tumorigenic properties, including abnormally rapid contact-independent growth, reduced ability to form cell-cell contacts and chromosomal aberrations. Ate1-KO fibroblasts can form large colonies in Matrigel and exhibit invasive behavior, unlike wild-type fibroblasts. Furthermore, Ate1-KO cells form tumors in subcutaneous xenograft assays in immunocompromised mice. Abnormal growth in these cells can be partially rescued by reintroduction of stably expressed specific Ate1 isoforms, which also reduce the ability of these cells to form tumors. Tumor array studies and bioinformatics analysis show that Ate1 is downregulated in several types of human cancer samples at the protein level, and that its transcription level inversely correlates with metastatic progression and patient survival. We conclude that Ate1-KO results in carcinogenic transformation of cultured fibroblasts, suggesting that in addition to its previously known activities Ate1 gene is essential for tumor suppression and also likely participates in suppression of metastatic growth. PMID- 26686092 TI - Metabolic reprogramming: a hallmark of viral oncogenesis. AB - More than 1 in 10 cases of cancer in the world are due to chronic viral infections. Viruses induce oncogenesis by targeting the same pathways known to be responsible for neoplasia in tumor cells, such as control of cell cycle progression, cell migration, proliferation and evasion from cell death and the host's immune defense. In addition, metabolic reprogramming has been identified over a century ago as a requirement for growth of transformed cells. Renewed interest in this topic has emerged recently with the discovery that basically all metabolic changes in tumor cells are finely orchestrated by oncogenes and tumor suppressors. Indeed, cancer cells activate biosynthetic pathways in order to provide them with sufficient levels of energy and building blocks to proliferate. Interestingly, viruses introduce into their host cells similar metabolic adaptations, and importantly, it seems that they depend on these changes for their persistence and amplification. The central carbon metabolism, for example, is not only frequently altered in tumor cells but also modulated by human papillomavirus, hepatitis B and C viruses, Epstein-Barr virus and Kaposi's Sarcoma-associated virus. Moreover, adenoviruses (Ad) and human cytomegalovirus, which are not directly oncogenic but present oncomodulatory properties, also divert cellular metabolism in a tumor cell-like mnner. Thus, metabolic reprogramming appears to be a hallmark of viral infection and provides an interesting therapeutic target, in particular, for oncogenic viruses. Therapeutic targeting of metabolic pathways may not only allow to eliminate or control the viral infection but also to prevent virus-induced carcinogenesis. PMID- 26686094 TI - Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis. AB - Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis. PMID- 26686095 TI - Nuclear trafficking of EGFR by Vps34 represses Arf expression to promote lung tumor cell survival. AB - Epidermal growth factor receptor (EGFR) is a cell surface receptor that has an essential role in cell proliferation and survival, and overexpression of EGFR is a common feature of human cancers. In Non-small-cell lung cancer (NSCLC), activating mutations of EGFR have also been described. We recently showed that mutant EGFR-L858R inhibits the expression of the p14ARF tumor-suppressor protein to promote cell survival. In this study, we defined the molecular bases by which EGFR controls Arf expression. Using various lung tumor models, we showed that EGF stimulation inhibits Arf transcription by a mechanism involving the nuclear transport and recruitment of EGFR to the Arf promoter. We unraveled the vesicular trafficking protein Vps34 as a mediator of EGFR nuclear trafficking and showed that its neutralization prevents the accumulation of EGFR to the Arf promoter in response to ligand activation. Finally, in lung tumor cells that carry mutant EGFR-L858R, we demonstrated that inhibition of Vps34 using small interfering RNA restrains nuclear EGFR location and restores Arf expression leading to apoptosis. These findings identify the Arf tumor suppressor as a new transcriptional target of nuclear EGFR and highlight Vps34 as an important regulator of the nuclear EGFR/Arf survival pathway. As a whole, they provide a mechanistic explanation to the inverse correlation between nuclear expression of EGFR and overall survival in NSCLC patients. PMID- 26686096 TI - Validity of the Ages and Stages Questionnaire to detect risk of Developmental Coordination Disorder in preschoolers. AB - BACKGROUND: A reliable and valid screening tool for detecting children at risk for Developmental Coordination Disorder (DCD) is needed. The purpose of this study was to evaluate the ability of the Ages and Stages Questionnaire-Third Edition (ASQ-3) motor scales to detect children at risk for DCD in a community based sample of children aged 3.5-5.5 years. METHODS: One hundred and sixty parent-child pairs were recruited from community-based organizations. Children were eligible if they spoke English and had no known physical impairments. Eligible parents were asked to fill out the ASQ-3, following which their child's fine motor and gross motor proficiency was assessed using the Movement Assessment Battery for Children-Second Edition (MABC-2). DCD risk was defined as those children scoring at or below the 16th percentile on the MABC-2. Sensitivity and specificity of the fine and gross motor areas of the ASQ-3 were examined and referenced against the DCD risk classification. RESULTS: The ASQ-3 total motor score correlated moderately with overall standard score on the MABC-2 (r = 0.41; p < 0.001). Regardless of the ASQ-3 cut-off used, sensitivities of the ASQ-3 fine motor or gross motor scale to detect DCD risk were low at 21-47%, whereas specificities were high at 89-96%. CONCLUSION: Early identification of motor skill delays is important in order to intervene and hopefully prevent the associated negative health consequences. However, because of the low sensitivity of the ASQ-3 motor scales, these results suggest that the ASQ-3 is not an appropriate screening tool to identify children at risk for DCD in the preschool population. PMID- 26686097 TI - Translation and validation of the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese. AB - OBJECTIVE: The aim of this study was to translate and validate the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese. METHODS: The translation/validation process was carried out through translation, back translation, technical review, assessment of verbal comprehension/clarity of the scale by experts and a focus group, test-retest, and application of the tool. The reproducibility analysis was performed by applying the PDSS in test-retest; internal consistency was verified by applying the scale in 90 children and adolescents. RESULTS: The mean score of the sum of PDSS questions was 15.6 (SD=5.0) points. The PDSS showed appropriate indicators of content validation and clarity for the Brazilian Portuguese version. The internal consistency analysis showed a Cronbach's alpha of 0.784. The PDSS showed adequate reproducibility. The PDSS scores showed a significant and negative correlation with time spent in bed (r=-0.214; p=0.023). CONCLUSION: The Brazilian Portuguese version of the PDSS shows satisfactory indicators of validity and can be applied in clinical practice and scientific research. PMID- 26686098 TI - Association between general and abdominal obesity with high blood pressure: difference between genders. AB - OBJECTIVE: To assess the association between general and abdominal obesity with high blood pressure in adolescents of both genders from the public school system. METHODS: This was an epidemiological, descriptive, exploratory study, with a quantitative approach and local scope whose sample consisted of 481 high school students (aged 14-19), selected by using a random cluster sampling strategy. Blood pressure was measured through the use of automated monitor and was considered high when the pressure values were at or above the 95th percentile. The analyses were performed using the chi-squared test and binary logistic regression. RESULTS: The prevalence of high blood pressure was 6.4%, and it was higher among boys (9.0% vs. 4.7%, p<0.05). There was no significant difference between general (p=0.903) and abdominal obesity (p=0.157) when genders were compared. After adjusting for age, high blood pressure was associated with general (OR=6.4; p<0.001) and abdominal obesity (OR=7.0; p<0.001) only among boys, when comparing the fourth quartile with the first quartile of body mass index (<= 18.6 kg/m(2)vs. >= 23.5 kg/m(2)) and waist circumference (<= 69 cm vs. >= 80.1cm). CONCLUSION: It was observed that general and abdominal obesity are associated with high blood pressure only in boys, regardless of age. PMID- 26686099 TI - Surface grafting of cellulose nanocrystals with natural antimicrobial rosin mixture using a green process. AB - Surface functionalization of cellulose nanocrystals (CNCs) aims to improve their properties. The main objective of this study was the esterification of the surface of CNCs using nontoxic resin acids, rosin. The structural and morphological modifications of CNC nanorods were characterized by (13)C NMR and Fourier transform infrared spectroscopy, atomic force microscopy, and X-ray diffraction analyses. The properties of functionalized CNCs were evaluated by thermogravimetric analysis and contact-angle measurements. The results indicate that the esterification proceeded from the surface of the CNC. The antimicrobial activities of the modified and neat CNC were investigated; the rosin-grafted CNC exhibited a strong antibacterial activity against Gram-negative bacteria and a modest antibacterial activity against Gram-positive bacteria. PMID- 26686100 TI - Development of rectal delivered thermo-reversible gelling film encapsulating a 5 fluorouracil hydroxypropyl-beta-cyclodextrin complex. AB - We have developed a novel 5-Fluorouracil (5FU) formulation for rectal application to improve its therapeutic efficiency in colorectal cancer. The results indicated that 5FU formed an inclusion complex with Hydroxypropyl-beta-Cyclodextrin (HP beta-CD). The stoichiometry of the complex was 1:1, with apparent stability constant of 100.4M(-1). After investigating physicochemical properties of the 5FU HP-beta-CD complex encapsulated with thermo-reversible gelling film, the optimized formulation P407/P188/HPMC/5FU-HP-beta-CD (18.5/2.5/0.2/15%) was selected and evaluated. The result showed that the 5FU-HP-beta-CD complex increased the solubility of 5FU, prolonged and enhanced its releasing. As compared to the raw drug, the transport efficiency of the 5FU-HP-beta-CD complex itself or entrapped in thermo-reversible gelling film were respectively 7.3- and 6.8-fold increased, and the cellular uptake of 5-FU 4.9- and 5.4-fold elevated. There was no irritation or damage to rectal sites in the 10h treatment period. Therefore, this HP-beta-CD based formulation might improve the therapeutic effect of 5FU on colon-rectal cancer. PMID- 26686101 TI - pH-sensitive polymeric micelles formed by doxorubicin conjugated prodrugs for co delivery of doxorubicin and paclitaxel. AB - A doxorubicin conjugated prodrug incorporated acid-sensitive linkage between drug and Pluronic F127-chitosan (F127-CS) polymer was successfully synthesized. Subsequently a pH-sensitive polymeric micelle system was designed based on the conjugated prodrugs (F127-CS-DOX) to co-deliver doxorubicin and paclitaxel. Paclitaxel (PTX) was physically entrapped in the hydrophobic inner core of the micelles simultaneously. The structures of conjugates were analyzed by means of (1)H NMR and UV-vis spectrum. Size distribution and morphology of the micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that obtained micelles had good dispersity and the diameter was between 56.3 and 403.4 nm. The loading of PTX into the micelle increased with higher DOX content. DOX and PTX release from polymeric micelles followed an acid-triggered manner. Furthermore, in vivo pharmacokinetic study also showed that the area under the plasma concentration time curve (AUC0-infinity) values of PTX and DOX for PTX-loaded F127-CS-DOX micelles in rats were 3.97 and 4.38-fold higher than those for PTX plus DOX solution. These results suggested the PTX-loaded F127-CS-DOX micelles would be a promising carrier for co-delivering DOX and PTX. PMID- 26686102 TI - Quality controlling of brown rice by ultrasound treatment and its effect on isolated starch. AB - Ultrasonic treatment (UT) was applied to brown rice at two different conditions: mild (25 degrees C, 30 min) and harsh (50 degrees C, 60 min) after soaking for several times (2, 3, 5, and 8h). After UT, starch was isolated from the brown rice grains, and the physicochemical properties of the starch, as well as the textural and nutritional properties of the grains, were compared. After UT, the cooked brown rice grains was softer in proportion to soaking time, and the hardness of brown rice soaked for 8h and then ultrasound treated at harsh condition was similar to that of cooked milled rice. Untreated brown rice grain has much more thiamin, riboflavin, and niacin contents than milled rice (0.546 vs. 0.069, 0.054 vs. 0.018, and 4.56 vs. 1.21 mg/100g, respectively), and the thiamin and niacin contents in brown rice treated even at the most harsh condition were still higher than those in milled rice (0.193 vs. 0.069, and 1.6 vs. 1.21 mg/100g, respectively). The isolated starch from brown rice grains treated at the harsh condition exhibited a lower pasting temperature and higher breakdown in pasting properties than that treated at the mild condition. The crystalline structure of starch became more homogeneous by UT at both conditions with longer soaking times. Both of the melting enthalpy and relative crystallinity of starch significantly decreased by UT, however A-type crystal form was maintained. PMID- 26686103 TI - Identification of a cytotoxic molecule in heat-modified citrus pectin. AB - Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin. PMID- 26686104 TI - Effects of Marsdenia tenacissima polysaccharide on the immune regulation and tumor growth in H22 tumor-bearing mice. AB - One water-soluble polysaccharide (Marsdenia tenacissima polysaccharide, MTP), with an average molecular weight of 4.9 * 10(4) Da, was isolated from the dried rattan of M. tenacissima. MTP contained 93.8% carbohydrates, 5.6% proteins and 21.3% uronic acid, and were composed of arabinose, mannose, galactose, xylose, glucuronic acid at a molar ratio of 9.1, 17.7, 30.2, 22.4 and 20.6. The experiments on the animals showed that MTP could increase the serum hemolysin, promote the formation of antibody-forming cells and improve the phagocytosis of mononuclear macrophage in normal mice. Meanwhile, MTP could also inhibit the growth of tumor in H22 tumor-bearing mice dose-dependently, and increase the spleen index, thymus index and serum albumin level in the mice. In addition, MTP could elevate the serum level of TNF-alpha and IL-2, increase the activity of GSH Px, CAT and SOD in the liver tissue, and reduce the content of VEGF and MDA. These results suggest that MTP can regulate the immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its antitumor activity may be related to its antioxidant and immunomodulatory effects. PMID- 26686105 TI - Biocompatible cellulose-based superabsorbent hydrogels with antimicrobial activity. AB - Current superabsorbent hydrogels commercially applied in the disposable diapers have disadvantages such as weak mechanical strength, poor biocompatibility, and lack of antimicrobial activity, which may induce skin allergy of body. To overcome these hassles, we have developed novel cellulose based hydrogels via simple chemical cross-linking of quaternized cellulose (QC) and native cellulose in NaOH/urea aqueous solution. The prepared hydrogel showed superabsorbent property, high mechanical strength, good biocompatibility, and excellent antimicrobial efficacy against Saccharomyces cerevisiae. The presence of QC in the hydrogel networks not only improved their swelling ratio via electrostatic repulsion of quaternary ammonium groups, but also endowed their antimicrobial activity by attraction of sections of anionic microbial membrane into internal pores of poly cationic hydrogel leading to the disruption of microbial membrane. Moreover, the swelling properties, mechanical strength, and antibacterial activity of hydrogels strongly depended on the contents of quaternary ammonium groups in hydrogel networks. The obtained data encouraged the use of these hydrogels for hygienic application such as disposable diapers. PMID- 26686106 TI - Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles. AB - The present investigation aimed at the fabrication and characterization of ionically cross-linked docetaxel (DTX) loaded chitosan nanoparticles (DTX-CH-NP) using ionic gelation technique with sodium tripolyphosphate (TPP) as the cross linking agent. The formulated nanoparticles were characterized in terms of particle size, drug entrapment efficiency (EE), scanning electron microscopy (SEM), in vitro release and cytotoxicity studies. Formulation factors (chitosan, TPP and drug concentration) were examined systematically for their effects on size of the nanoparticles. The average size of the nanoparticles was observed to be in the range of 159.2 +/- 3.31 to 220.7 +/- 2.23 nm with 78-92% encapsulation efficiency (EE). The in vitro cytotoxicity studies on breast cancer cell lines (MDA-MB-231) revealed the advantages of DTX-CH-NP over pure DTX with approximately 85% cell viability reduction. The results indicate that systematic modulation of the surface charge and particle size of ionically cross-linked nanoparticles can be readily achieved with the right control of critical processing parameters. Thus, DTX-CH-NP presents a promising delivery alternative for breast cancer treatment. PMID- 26686107 TI - Competitive fluorescence assay for specific recognition of atrazine by magnetic molecularly imprinted polymer based on Fe3O4-chitosan. AB - A novel fluorescence sensing strategy for determination of atrazine in tap water involving direct competition between atrazine and 5-(4,6-dichlorotriazinyl) aminofluorescein (5-DTAF), and which exploits magnetic molecularly imprinted polymer (MMIP), has been developed. The MMIP, based on Fe3O4-chitosan nanoparticles, was synthesized to recognize specific binding sites of atrazine. The recognition capability and selectivity of the MMIP for atrazine and other triazine herbicides was investigated. Under optimal conditions, the competitive reaction between 5-DTAF and atrazine was performed to permit quantitation. Fluorescence intensity changes at 515 nm was linearly related to the logarithm of the atrazine concentration for the range 2.32-185.4 MUM. The detection limit for atrazine was 0.86MUM (S/N=3) and recoveries were 77.6-115% in spiked tap water samples. PMID- 26686108 TI - Preparation, characterization and evaluation of antibacterial activity of catechins and catechins-Zn complex loaded beta-chitosan nanoparticles of different particle sizes. AB - This study used beta-chitosan nanoparticles (beta-CS NPs) of different particle sizes to encapsulate catechins (CAT) or CAT-Zn complex by ionic gelation technology. The antibacterial activity of CAT or CAT-Zn complex loaded beta-CS NPs against Escherichia coli and Listeria innocua were investigated based on bacterial growth curve, minimum inhibitory concentration (MIC), and minimum bacterial concentration (MBC). Fourier transform infrared spectrometer (FT-IR) was employed to study the incorporation of CAT or CAT-Zn complex into beta-CS NPs. The CAT-Zn complex loaded beta-CS NPs had particle size of 208-591 nm, polydispersity index (PDI) of 0.377-0.395, and positive Zeta-potential of 39.17 45.62 mV. The CAT-Zn complex loaded beta-CS NPs of smaller particle sizes showed higher antibacterial activity than that of larger particle size ones. The MIC and MBC of CAT-Zn complex loaded beta-CS NPs of the smallest particle size against L. innocua and E. coli were 0.031 and 0.063 mg/mL, and 0.063 and 0.125 mg/mL, respectively. This study suggested that encapsulation of CAT-Zn complex in beta CS NPs improved the antibacterial activity of CAT and CAT-Zn complex, and the encapsulators have great potential to be used as antibacterial substances for food and other applications through either direct addition or incorporation into packaging materials. PMID- 26686109 TI - Preparation and properties of environmental-friendly coatings based on carboxymethyl cellulose nitrate ester & modified alkyd. AB - Amphipathic coating basic film-forming material carboxymethyl cellulose nitrate ester (CMCN) was synthesized and characterizations of CMCN with different ratio of functional groups were studied. Ratios of functional groups on each repeating units of CMCN have great importance in the decision of CMCN properties using as an amphipathic coating basic film-forming material and ratios of functional groups were the most concerned of the study. Ratios of functional groups on each repeating units of CMCN were measured by elemental analyzer and calculated. Series of experiments were conducted using different ratios of functional groups of CMCN. Thermal properties of CMCN were measured by FT-IR and TG. Densities of CMCN powders were measured. Aqueous coatings based on CMCN/alkyd (after chemical modified by coconut oil) were prepared and morphology & rheology of CMCN hydrophilic dispersions were measured using an Anton-Paar-Strasse 20A-8054 Graz analyzer. Contact angles between films based on CMCN and deionized water were recorded. Other properties of films were measured. CMCN with the etherification of carboxymethyl groups at 0.35-0.40, nitrate ester groups at 1.96-2.19 and hydroxyl groups at 0.46-0.64 per d-glucose was considered as the best film forming material. PMID- 26686110 TI - Gastroretentive extended release of metformin from methacrylamide-g-gellan and tamarind seed gum composite matrix. AB - Formulation of a gastroretentive extended release tablet of metformin based on polymethacrylamide-g-gellan (Pmaa-g-GG)-tamarind seed gum (TSG) composite matrix is the main purpose of this study. Tablets were prepared employing wet granulation method taking amount of Pmaa-g-GG, TSG and NaHCO3 (SBC, buoyancy contributor) as independent formulation variables. The tablets were then evaluated for in vitro drug release, buoyancy, ex vivo mucoadhesion, swelling and surface morphology. Compatibility between drug and excipients was checked by DSC, FTIR and XRD analysis. Buoyancy-lag-time, mucoadhesive strength, % drug release and release-rate constant were statistically analyzed using Design-Expert software (version 9.0.4.1) and the formulation was then numerically optimized to obtain USP-reference release profile. The optimized formulation showed excellent buoyancy over a 10h period with buoyancy lag time of 2.76min, significant mucoadhesion and drug release over a period of 10h with f2=71.58. Kinetic modeling unveiled anomalous non-Fickian transport based drug release mechanism. PMID- 26686111 TI - Fabrication and characterization of novel starch-grafted poly l-lactic acid/montmorillonite organoclay nanocomposites. AB - In this work, poly(L-lactic acid)-g-starch layered silicate nanocomposites (NCs) (PLLA-g-starch/MMT) were fabricated by intercalative bulk graft copolymerization of LA with starch, in the presence of either stannous octoate acting as a catalyst or LA-MMT organoclay acting as a cocatalyst-nanofiller. This procedure was performed inside a custom vacuum micro-reactor. To better understand the graft copolymerization mechanism, in situ processing types, interfacial interactions and nanostructure formation of PLLA-g-starch/MMT NCs, methods such as FT-IR, XRD, (1)H NMR, (13)C CP/MAS-NMR, DSC/TGA, TEM and SEM were utilized. The morphology and thermal behaviors of nanocomposites were found to be strongly dependent on the loading mass fraction of LA-MMT within the nanocomposite structure and the type of in situ processing such as interfacial, physical and chemical interactions. Preintercalated LA-MMT organoclay exhibited dual functions. It demonstrated the ability to act as a catalyst, essentially accelerating in situ graft copolymerization via esterification of LA carboxyl groups with hydroxyl groups of starch macromolecules, whilst also acting as a nananofiller-compatibilizer. PMID- 26686112 TI - Highly efficient chromium(VI) adsorption with nanofibrous filter paper prepared through electrospinning chitosan/polymethylmethacrylate composite. AB - Chitosan/polymethylmethacrylate (PMMA) composite nanofibrous membrane was prepared by electrospinning technique with a single solvent system. Characterization with Fourier transformation infrared spectroscopy (FT-IR) indicated that there was weak interaction (such as hydrogen bonds) between PMMA and chitosan. Scanning electron microscopy (SEM) measurements illustrated that the average diameter of the composite nanofibers decreased as the chitosan content was increased, while the number of nano/micrometer sized beads increased in the membrane. The composite nanofibrous membrane with chitosan:PMMA ratio of 0.3:1.0 exhibited a maximum adsorption capacity (67.0 mg g(-1)) of Cr(VI) in static adsorption, which was nearly three times higher than that of chitosan powder (22.9 mg g(-1)). The adsorption capacity of Cr(VI) via filtration became even higher, where the maximum value was 92.5 mg g(-1) at pH 3.0. Notably, most of Cr(VI) has been removed after the first filtration at all pH values (2.0-6.0) investigated in this report. The adsorption capacity of the composite nanofibrous membrane decreased slightly (17.1%) after three filtration cycles even with the solution of pH 2.0, which shall be attributed to the enhanced mechanical strength and acid fastness of the composite membrane. X-ray photoelectron spectroscopy (XPS) analysis indicated that amino groups played an important role in the adsorption of Cr(VI). PMID- 26686113 TI - Utilization of starch films plasticized with urea as fertilizer for improvement of plant growth. AB - The utilization of starch films, obtained by extrusion of potato starch with urea as plasticizer, for the fertilization of plants has been undertaken. Release rate of urea from the starch films was conducted in water conditions. The molecular weight distribution, surface erosion and weight loss of the starch samples have been determined. The evaluation of efficiency of urea as a fertilizer in the process of release from the starch films was performed under laboratory conditions based on the plant growth test proposed by OECD 208 Guideline and the PN-ISO International Standard using oat and common radish. Although among extruded starch-based films, those that contain the highest amount of fertilizer hold the most promise for a delayed release system, the time of release of fertilizer from obtained films in undertaken study was not satisfactory. All the same, in the present study effort has been made to utilize extruded samples as a fertilizer for agriculture or horticulture purposes. Urea-plasticized starch was successfully used as a fertilizer. Plant growth assessment, including determination of such parameters as fresh and dry matter of plants and their visual evaluation, has proved the stimulating effect of using extruded films on the growth and development of cultivated plants. PMID- 26686114 TI - Chitosan hydrogel beads impregnated with hexadecylamine for improved reactive blue 4 adsorption. AB - Adsorption performance of chitosan (CS) hydrogel beads was investigated after impregnation of CS with hexadecylamine (HDA) as a cationic surfactant, for the elimination of reactive blue 4 (RB4) from wastewater. The CS/HDA beads formed with 3.8% HDA were the most effective adsorbent. The adsorption capacity was increased by 1.43 times from 317 mg/g (CS) to 454 mg/g (CS/HDA). The RB4 removal increased with decrease in the pH of dye solution from 4 to 9. The isotherm data obtained from RB4 adsorption on CS and CS/HDA are adequately described by Freundlich model (R(2)=0.946 and 0.934, chi(2)=22.414 and 64.761). The kinetic study revealed that the pseudo-second-order rate model (R(2)=0.996 and 0.997) was in better agreement with the experimental data. The negative values of DeltaG degrees (-2.28 and -6.30 kJ/mol) and DeltaH degrees (-172.18 and -101.62 kJ/mol) for CS beads and HDA modified CS beads, respectively; suggested a spontaneous and exothermic process for RB4 adsorption. PMID- 26686115 TI - Particle size distribution of wheat starch granules in relation to baking properties of frozen dough. AB - The impact of freezing on the wheat starches with different particle size was studied using a range of characterization methods including X-ray diffraction, differential scanning calorimetry, the Rapid Visco Analyser and a reconstitution dough system. Wheat starches were fractionated into A- and B-type granules, and then subjected to freezing/thawing treatment for 3 cycles. The freezing treatment did not cause apparent damage on A-type granular surface but induced cracked structure on B-type granules. It facilitated materials such as amylose, proteins, and lipids leaching from starch granule and an increase in gelatinization temperatures, melting enthalpy, and pasting viscosities. A smaller bread specific volume was obtained from freezing-treated B-granules while the crumb firmness significantly increased (p>0.05). No marked differences were observed in the counterparts of A-granules after freezing treatment. It seemed that the B-type granules were more sensitive to the freezing/thawing treatment, thus facilitating structural transformations from dough to bread. Results indicated that the deterioration in frozen bread quality derived from starch could be minimized by increasing the A-granules content. PMID- 26686116 TI - Structural characterization and antioxidant activity in vitro of polysaccharides from angelica and astragalus. AB - In the present study, structural characterization and antioxidant activity of a fraction (AAP-2A) of polysaccharides from angelica and astragalus (AAP) were investigated. Characteriztion assay showed that AAP-2A had molecular weight (Mw), root-mean square (RMS) radius and polydispersity index (Mw/Mn) of 2.252 * 10(3)kDa, 28.4 nm and 1.038, respectively. There were infrared characteristic absorption peaks of polysaccharides in FT-IR spectroscopy. AAP-2A was composed of rhamnose (Rha), galactose (Gal), arabinose (Ara) and glucose (Glc) with a molar ratio of 1:2.13:3.22:6.18 in GC analysis. Methylation analysis combined with NMR spectroscopic analysis demonstrated that a preliminary structure of AAP-2A was proposed as follows: 1,3-linked Rhap, 1,3-linked Galp, 1,3-linked Araf, 1,5 linked Araf, 1,3,5-linked Araf, 1,4-linked Glcp and 1,4,6-linked Glcp interspersed with terminal Glcp. AAP-2A exhibited a surface with a sheet-like appearance in scanning electron microscope and stronger antioxidant capacity compared with AAP. PMID- 26686117 TI - Effect of stearic acid-grafted starch compatibilizer on properties of linear low density polyethylene/thermoplastic starch blown film. AB - The present work aims to investigate the effect of stearic acid-grafted starch (ST-SA) on the rheological, thermal, optical, dynamic mechanical thermal, and tensile properties of linear low density polyethylene/thermoplastic starch (LLDPE/TPS) blends, as well as on their water vapor and oxygen barrier properties. Blends consisting of LLDPE and TPS in a weight ratio of 60:40 and ST SA at different concentrations, i.e. 1, 3 and 5%, were prepared using a twin screw extruder. The obtained resins were subsequently converted into films via blown film extrusion. Incorporation of ST-SA resulted in a decreased degree of shear thinning, reduced ambient temperature elasticity, and improved tensile strength, secant modulus, extensibility, and UV absorption, as well as diminished water vapor and oxygen permeabilities of the LLDPE/TPS blend. These effects are attributed to the enhanced interfacial adhesion between LLDPE and TPS phases through the compatibilizing effect induced by ST-SA, and the good dispersion of the TPS phase in the LLDPE matrix. The results confirmed that ST-SA could potentially be used as a compatibilizer for the LLDPE/TPS blend system. PMID- 26686118 TI - Cellulose nanocrystal reinforced oxidized natural rubber nanocomposites. AB - Natural rubber (NR) latex particles were oxidized using KMnO4 as oxidant to promote the insertion of hydroxyl groups in the surface polyisoprene chains. Different degrees of oxidation were investigated. Both unoxidized and oxidized NR (ONR) latex were used to prepare nanocomposite films reinforced with cellulose nanocrystals (CNCs) by casting/evaporation. The oxidation of NR was carried out to promote chemical interactions between the hydroxyl groups of ONR with those of CNCs through hydrogen bonding. The effect of the degree of oxidation of the NR latex on the rheological behavior of CNC/NR and CNC/ONR suspensions, as well as on the mechanical, swelling and thermal properties of ensuing nanocomposites was investigated. Improved properties were observed for intermediate degrees of oxidation but they were found to degrade for higher oxidation levels. PMID- 26686119 TI - Chitosan crosslinked with genipin as support matrix for application in food process: Support characterization and beta-D-galactosidase immobilization. AB - In order to develop safer processes for the food industry, we prepared a chitosan support with the naturally occurring crosslinking reagent, genipin, for enzyme. As application model, it was tested for the immobilization of beta-D galactosidase from Aspergillus oryzae. Chitosan particles were obtained by precipitation followed by adsorption of the enzyme and crosslinking with genipin. The particles were characterized by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The immobilization of the enzyme by crosslinking with genipin provided biocatalysts with satisfactory activity retention and thermal stability, comparable with the ones obtained with the traditional methodology of immobilization using glutaraldehyde. beta-D Galactosidase-chitosan-genipin particles were applied to galactooligosaccharides synthesis, evaluating the initial lactose concentration, pH and temperature, and yields of 30% were achieved. Moreover, excellent operational stability was obtained, since the immobilized enzyme maintained 100% of its initial activity after 25 batches of lactose hydrolysis. Thus, the food grade chitosan-genipin particles seem to be a good alternative for application in food process. PMID- 26686120 TI - An investigation of Pseudomonas aeruginosa biofilm growth on novel nanocellulose fibre dressings. AB - Nanocellulose from wood is a novel biomaterial, which is highly fibrillated at the nanoscale. This affords the material a number of advantages, including self assembly, biodegradability and the ability to absorb and retain moisture, which highlights its potential usefulness in clinical wound-dressing applications. In these in vitro studies, the wound pathogen Pseudomonas aeruginosa PAO1 was used to assess the ability of two nanocellulose materials to impair bacterial growth (<48 h). The two nanocelluloses had a relatively small fraction of residual fibres (<4%) and thus a large fraction of nanofibrils (widths <20 nm). Scanning electron microscopy and confocal laser scanning microscopy imaging demonstrated impaired biofilm growth on the nanocellulose films and increased cell death when compared to a commercial control wound dressing, Aquacel((r)). Nanocellulose suspensions inhibited bacterial growth, whilst UV-vis spectrophotometry and laser profilometry also revealed the ability of nanocellulose to form smooth, translucent films. Atomic force microscopy studies of the surface properties of nanocellulose demonstrated that PAO1 exhibited markedly contrasting morphology when grown on the nanocellulose film surfaces compared to an Aquacel((r)) control dressing (p<0.05). This study highlights the potential utility of these biodegradable materials, from a renewable source, for wound dressing applications in the prevention and treatment of biofilm development. PMID- 26686121 TI - Organocatalytic route for the synthesis of propionylated starch. AB - In recent years acetylated, propionylated and butyrylated starches have received special attention due to their capacity to deliver specific short chain fatty acids (SCFAs) to the colon in a sustained and predictable manner, and thus contribute to maintaining the normal physiologic function of the large bowel and preventing specific diseases. In the current contribution a non-conventional organocatalytic solventless route for the eco-friendly propionylation of corn starch is proposed. The catalyst used in the acylation is a naturally occurring alpha-hydroxy acid (l-tartaric acid). Propionylated starches with degree of substitution (DS) in the 0.05-1.59 interval were obtained and characterized in terms of chemical structure, morphology, crystallinity, thermal stability and hydrophilicity. Results showed that by the proposed methodology propionylated starch with the DS required for clinical use (i.e. 0.2-0.3) could be obtained within 2-3h of reaction. Characterization results evidenced the progressive loss of crystallinity of starch granules as higher substitution levels were conferred. PMID- 26686122 TI - Microscopic and spectroscopic analysis of chitosan-DNA conjugates. AB - Conjugations of DNA with chitosans 15 kD (ch-15), 100 kD (ch-100) and 200 kD (ch 200) were investigated in aqueous solution at pH 5.5-6.5. Multiple spectroscopic methods and atomic force microscopy (AFM) were used to locate the chitosan binding sites and the effect of polymer conjugation on DNA compaction and particle formation. Structural analysis showed that chitosan-DNA conjugation is mainly via electrostatic interactions through polymer cationic charged NH2 and negatively charged backbone phosphate groups. As polymer size increases major DNA compaction and particle formation occurs. At high chitosan concentration major DNA structural changes observed indicating a partial B to A-DNA conformational transition. PMID- 26686123 TI - Controlled release of acetylsalicylic acid from polythiophene/carrageenan hydrogel via electrical stimulation. AB - Blends between polythiophene (PTh) and a carrageenan hydrogel were fabricated as the matrix for the electric field assisted drug release. The pristine carrageenan and the blend films were prepared by the solution casting using acetylsalicylic acid (ASA) as the anionic model drug and Mg(2+), Ca(2+), and Ba(2+) as the crosslinking agents. The ASA was released by the Fickian diffusion mechanism. The diffusion coefficient decreased with increasing crosslinking ratio or decreasing crosslinking ionic radii. The diffusion coefficients were greater with the applied electrical potentials by an order of magnitude relative to those without electric field. Moreover, the diffusion coefficients with PTh as the drug carrier were higher than those without PTh. Thus, the presence of the conductive polymer in the hydrogel blend coupled with applied electric field is shown here to drastically enhance the drug delivery rate. PMID- 26686124 TI - N,N,N-trimethylchitosan modified with well defined multifunctional polymer modules used as pDNA delivery vector. AB - A novel non-viral gene carrier based on N,N,N-trimethylchitosan (TMC) has been fabricated. First, well-defined copolymer P(PEGMA-co-DMAEMA) was synthesized through reversible addition fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and N,N-(2 dimethylamino)ethyl methacrylamide (DMAEMA). Then allyl group grafting N,N,N trimethylchitosan (Allyl-TMC) was synthesized via the reaction between allyl bromide and hydroxyl of TMC. Finally, P(PEGMA-co-DMAEMA) and folate were ordinally grafted onto Allyl-TMC to obtain TMC-g-P(PEGMA-co-DMAEMA)-FA. In comparison with pristine chitosan, TMC-g-P(PEGMA-co-DMAEMA)-FA has achieved both better water solubility and stronger pDNA packaging ability, which can contribute to improving gene transfection. Gene delivery efficiency of a series of TMC based functional polymers with different chitosan molecular weights has been tested. The results show that 20k-TMC-g-P(PEGMA-co-DMAEMA)-FA/pDNA complex at the weight ratio of 20 achieve the highest transfection efficiency in 293 T cells. This work presents a new strategy to modify chitosan efficiently as gene carrier material. PMID- 26686125 TI - Hydrophobic lappaconitine loaded into iota-carrageenan by one step self-assembly. AB - New data on the loading of pH-sensitive lappaconitine loaded into iota carrageenan (LA-ICG) is provided. This LA-ICG ionic biopolymer was prepared by one step self-assembly. The LA-ICG was characterized in terms of the loading capacity, lappaconitine (LA) releasing behavior, pH-sensitivity, and analgesic properties. Iota-carrageenan (ICG) high loading capacity reached up to 26.18% (w/w). Also, the LA, loaded with ICG, was released faster in an acidic environment than that in neutral or alkaline environments. Animal analgesic experiments showed that the LA-ICG of low molecular weight had earlier onset time and longer duration than the LA. These results suggest that the ICG of low molecular weight has great potential to achieve the synergistic effect of LA. In addition, the ICG can be used as a novel natural polymeric carrier for loading a hydrophobic alkaloid. PMID- 26686126 TI - Synergistic effect of cellulose nanocrystals/graphene oxide nanosheets as functional hybrid nanofiller for enhancing properties of PVA nanocomposites. AB - Novel functional hybrid nanofillers composed of cellulose nanocrystals (CNC) and graphene oxide nanosheets (GON), at different weight ratios (2:1, 1:1 and 1:2), were successfully prepared and characterized, and their synergistic effect in enhancing the properties of poly(vinyl alcohol) (PVA) nanocomposites was investigated. Due to the synergistic reinforcement, it was found that the Young's modulus, tensile strength and toughness of the PVA nanocomposite containing 5 wt% hybrid nanofiller (1:2) were significantly improved by 320%, 124% and 159%, respectively; and the elongation at break basically remained compared to the neat PVA matrix. In addition, the glass and melting temperatures as well as the moisture sorption of nanocomposites were also enhanced. This synergistic effect improved the dispersion homogeneity by avoiding the agglomeration phenomenon of nanofillers within the polymer matrix, resulting in nanocomposites with largely enhanced properties compared to those prepared from single nanofiller (CNC or GON). The preparation of these hybrid nanofillers and their incorporation into a polymer provided a novel method for the development of novel multifunctional nanocomposites based on the combination of existing nanomaterials. PMID- 26686127 TI - Effect of active edible coatings made by basil seed gum and thymol on oil uptake and oxidation in shrimp during deep-fat frying. AB - The effect of active coating treatments on oil uptake, moisture loss, lipid oxidation, texture, color, and sensory evaluation of shrimp after deep-fat frying process was investigated. Compared with the uncoated samples, coating treatments decreased the oil uptake and moisture loss of fried shrimp by 34.50 and 13.9%, respectively. Fried shrimp samples were analyzed for peroxide value (PV) and thiobarbituric acid (TBA). The most reduction in lipid oxidation (46.4% for PV and 40.8% for TBA) was observed when shrimp samples were coated with CS4 (containing 10% thyme), while the control samples had the highest values of PV and TBA after deep-fat frying process. Coated fried samples had significantly lower toughness and stiffness than control samples (P<0.05). In terms of sensory evaluation, there was no significant difference in color, smell, and taste among the treatments (P>0.05). However, for the texture, juiciness, chewiness, and overall acceptability, coated fried samples had higher scores than control. PMID- 26686128 TI - Synthesis of photo-crosslinkable hyaluronan with tailored degree of substitution suitable for production of water resistant nanofibers. AB - In this work, hyaluronan (HA) was grafted by a novel and an efficient mixed anhydrides methodology with (hetero)-aryl and aliphatic acrylic moieties suitable for cross-linking. A precise control of stoichiometry was achieved. Derivatives with degree of substitution (DS) below 20% did not show self-crosslinking. Due to mild reaction conditions, a negligible degradation of the polysaccharide was obtained. The influence of the feed components on the reaction efficiency and DS were studied up to 200 g/batch. The structure of the modified HA was characterized by Infrared Spectroscopy, Nuclear Magnetic Resonance, SEC-MALS and chromatographic analyses. Enzymatic degradation of derivatives was performed and isolated dimers demonstrated to be non-cytotoxic. The feasibility of the grafted HA for electrospinning with subsequent photo-crosslinking to avoid nanofibers water dissolution was demonstrated. The biocompatibility of the material, its degradation products, and the formation of honeycomb porous structures also proved the potential of the material for future in vivo applications. PMID- 26686129 TI - Preparation and characterization of cotton fabric with potential use in UV resistance and oil reclaim. AB - Here we report a simple, facile and low-cost approach to the cotton textile with significant properties. After treatment, the cotton textiles exhibit not only an excellent superhydrophobicity with the water contact angle (WCA) of 151.5(o), but also an efficient shielding property against UV with the transmittance under 2.0%. More importantly, this cotton displays an outstanding potency in oil reclaim, which can recycle oil from the waste water with oil stain efficiently. Apparently, our results suggest an innovative material that should find practical and diversified applications, particularly in the field of oil spill cleanup. PMID- 26686130 TI - Regenerated bacterial cellulose microfluidic column for glycoproteins separation. AB - To analysis and separate glycoproteins, a simple strategy to prepare regenerated bacterial cellulose (RBC) column with concanavalin A (Con A) lectin immobilized in microfluidic system was applied. RBC was filled into microchannel to fabricate RBC microcolumn after bacterial cellulose dissolved in NaOH-sulfourea water solution. Lectin Con A was covalently connected onto RBC matrix surface via Schiff-base formation. Lysozyme (non-glycoprotein) and transferrin (glycoprotein) were successfully separated based on their different affinities toward the immobilized Con A. Overall, the RBC microfluidic system presents great potential application in affinity chromatography of glycoproteins analysis, and this research represents a significant step to prepare bacterial cellulose (BC) as column packing material in microfluidic system. What is more, troublesome operations for lectin affinity chromatography were simplified by integrating the microfluidic chip onto a HPLC (High Performance Liquid Chromatography) system. PMID- 26686131 TI - C6-Modifications on chitosan to develop chitosan-based glycopolymers and their lectin-affinities with sigmoidal binding profiles. AB - Chitosan-based glycopolymers having multiple beta-lactosides exclusively at their C6-positions were successfully synthesized from partially deacetylated chitin through perfect N-deacetylation/phthaloylation and C6-selective bromination/azidation to afford 6-azide-6-deoxy-N-phthaloyl-chitosan and the subsequent Cu(+)-catalyzed Huisgen cycloadditions using alkyne-terminated beta lactoside and/or quaternary ammonium modules followed by dephthaloylations. Lectin-affinities of the resultant chitosan-based glycopolymers were assessed through fluorescence titration assays to show their unique sigmoidal binding profiles with amplified binding constants. PMID- 26686132 TI - Single chain morphology and nanofiber-like aggregates of branched beta-(1 -> 3)-D glucan in water/dimethylsulfoxide solution. AB - A polysaccharide coded as PR-CA was extracted from Polyporus rhinoceros and determined to be a beta-(1 -> 3)-D-glucan with multiple branches. The weight average molecular weights (Mw) of PR-CA in dimethylsulfoxide (DMSO) and in water were determined with static light scattering (SLS) to be 3.57 * 10(5) and 1.79 * 10(7), indicating existence of the single chains in DMSO and co-existence of single chains and aggregates in water. Moreover, the stiffness of single chains of PR-CA in water was directly visualized by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The hollow structure of PR-CA nanofibers with width of 30-40 nm and length of ~ 350 nm formed in the water/DMSO (9:1, v:v) was demonstrated by a fluorescent probe tetraphenylethylene (TPE) via aggregation induced emission (AIE). The formation of PR-CA nanofibers was ascribed to the parallel aggregation of the extended PR-CA chains due to the hydrogen bonding and hydrophobic interaction. This work offered valuable results for promising applications of natural branched beta-glucans in the biological fields of drug inclusion, delivery and disease diagnosis. PMID- 26686133 TI - Development and physicochemical characterization of alginate composite film loaded with simvastatin as a potential wound dressing. AB - Previously, studies have demonstrated that topical application of simvastatin can promote wound healing in diabetic mice via augmentation of angiogenesis and lymphangiogenesis. This study aimed to formulate and characterize simvastatin in alginate-based composite film wound dressings. Biopolymers used for composite films were sodium alginate blended with pectin or gelatin. The films were prepared and characterized based on their physical properties, surface morphology, mechanical strength and rheology. Then, in vitro drug releases from the films were investigated and, finally, the cell viability assay was performed to assess the cytotoxicity profile. From the pre-formulation studies, alginate/pectin composite film showed to possess desirable wound dressing properties and superior mechanical properties. The in vitro drug release profile revealed that alginate/pectin film produced a controlled release drug profile, and cell viability assay showed that the film was non-toxic. In summary, alginate/pectin composite film is suitable to be formulated with simvastatin as a potential wound dressing. PMID- 26686134 TI - Preparation and physicochemical properties of three types of modified glutinous rice starches. AB - Hydroxypropylated, phosphorylated, and hydroxypropyl-phosphorylated starches were prepared from glutinous rice starch, and their physicochemical and structural properties were investigated. With increasing reaction time, the molar or degree of substitution of modified starches increased. SEM micrographs revealed that phosphorylated starch granules retained their relative integrity, while some cracks appeared on the surface of hydroxypropylated and hydroxypropyl phosphorylated starch granules. RVA analyses revealed that pasting properties improved after chemical modification. Additionally, chemical modification improved freeze-thaw stability, especially in hydroxypropyl-phosphorylated starch. DSC analyses showed that onset temperature and gelatinization enthalpy decreased with increasing reaction time, especially in the dual-modified starch. X-ray diffraction patterns revealed that native and modified starches had A-type crystalline patterns. FT-IR spectra showed some minor spectral differences after modification. (13)C CP/MAS NMR spectra showed that a novel peak appeared at 20 ppm after hydroxypropylation and that the relative intensity signals in the C4 region increased after phosphorylation. PMID- 26686135 TI - Synthesis and characterization of amylose-zinc inclusion complexes. AB - Amylose-zinc inclusion complexes were synthesized using zinc chloride and amylose, which is obtained by completely debranching potato starch using pullulanase. Based on the zinc content (W-Zn) and zinc conversion (C-Zn), the reaction parameters, such as reaction time, reaction temperature, pH value and amount of zinc chloride added, were evaluated. The W-Zn and C-Zn of the zinc loaded amylose, which was prepared under optimal conditions, were 128 mg/g and 82.05%, respectively. The Raman spectra showed that amylose formed a special single helix structure after complexing with zinc. X-Ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) results showed that starch and zinc could formate the inclusion complexes. Moreover, the formation of amylose-zinc inclusion complexes was confirmed by the results of X-ray photoelectron spectroscopy (XPS) and (13)C CP/MAS NMR, which suggests that zinc was mainly coordinated to the oxygen atoms of the glucose unit, 6-CH2OH. Thermal properties of the complexes were influenced by the zincatation process. This approach not only enlarged the number of fields for amylose use but also exhibited the extensive potential applications for zinc nutrition fortifier research. The study suggested that potato amylose might be a good carrier of zinc for nutritional supplementation purposes. PMID- 26686136 TI - Highly ordered cellulose II crystalline regenerated from cellulose hydrolyzed by 1-butyl-3-methylimidazolium chloride. AB - This research focused on the preparation of highly ordered cellulose II crystalline by cellulose hydrolysis in ionic liquid, and the influence of molecular mobility on recrystallization of cellulose. The molar mass of cellulose was controlled by hydrolysis using 1-butyl-3-methylimidazolium chloride (BmimCl). The molecular mobility of cellulose dissolved in BmimCl was characterized by rheological properties. After characterization of cellulose solution and regeneration, change of molar mass and conversion to crystalline were monitored using gel-permeation chromatography and powder X-ray diffraction, respectively. The molar mass of the cellulose in BmimCl was remarkably decreased with an increase in duration time, resulting in better mobility and a lower conformational constraint below critical molar mass. The decrease in molar mass surprisingly increased the crystallinity up to ~ 85%, suggesting a recrystallization rate dependence of the mobility. The correlation between the mobility and recrystallization rate represented quit different behavior above and below a critical molar mass, which strongly demonstrated to the effect of mobility on the conversion of amorphous state to crystalline structure. PMID- 26686137 TI - Physicochemical properties of quinoa starch. AB - Physicochemical properties of quinoa starches isolated from 26 commercial samples from a wide range of collection were studied. Swelling power (SP), water solubility index (WSI), amylose leaching (AML), enzyme susceptibility, pasting, thermal and textural properties were analyzed. Apparent amylose contents (AAM) ranged from 7.7 to 25.7%. Great variations in the diverse physicochemical properties were observed. Correlation analysis showed that AAM was the most significant factor related to AML, WSI, and pasting parameters. Correlations among diverse physicochemical parameters were analyzed. Principal component analysis using twenty three variables were used to visualize the difference among samples. Six principal components were extracted which could explain 88.8% of the total difference. The wide variations in physicochemical properties could contribute to innovative utilization of quinoa starch for food and non-food applications. PMID- 26686138 TI - Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability. AB - The present study was envisaged to evaluate the effect of erlotinib beta cyclodextrin nanosponge (ERL-NS) on the solubility, dissolution, in vitro cytotoxicity and oral bioavailability of erlotinib (ERL). Preliminary studies were conducted to select the optimized stoichiometry concentration of ERL and NS. The drug nanosponge complex comprising of 1:4 proportions of ERL and NS was prepared by freeze drying. ERL-NS formed nanoparticles of 372 +/- 31 nm size with narrow size distribution (0.21 +/- 0.07 PDI) and high zeta potential (-32.07 +/- 4.58 mV). The complexation phenomenon was confirmed by DSC, SEM, PXRD, FTIR, and TEM studies. In vitro dissolution studies revealed an increased dissolution rate (2-folds) with an enhanced dissolution efficiency of the nanosponge complex in comparison to pure drug. In vitro cytotoxicity study and apoptosis assay in pancreatic cell lines (MIA PaCa-2 and PANC-1) indicates the increased toxicity of ERL-NS. Both, quantitative and qualitative cell uptake studies unveiled the higher uptake efficiency of ERL-NS than free drug. ERL-NS showed enhanced oral bioavailability with 1.8-fold higher Cmax (78.98 +/- 6.2 vs. 42.36 +/- 1.75 MUg/ml), and ~ 2-fold AUC0-infinity (1079.95 +/- 41.38 vs. 580.43 +/- 71.91), in comparison to pure ERL. Therefore, we conclude that the formation of a complex of nanosponge with ERL is a successful approach to increase its solubility, dissolution and oral bioavailability which may ultimately result in reduction in dose and dose related side-effects. PMID- 26686139 TI - Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs. AB - The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis((r)), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis((r)) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization. PMID- 26686140 TI - Development of edible films and coatings from alginates and carrageenans. AB - The use of renewable resources, which can reduce waste disposal problems, is being explored to produce biopolymer films and coatings. Renewability, degradability, and edibility make such films particularly suitable for food and nonfood packaging applications. Edible films and coatings play an important role in the quality, safety, transportation, storage, and display of a wide range of fresh and processed foods. They can diminish main alteration by avoiding moisture losses and decreasing adverse chemical reaction rates. Also, they can prevent spoilage and microbial contamination of foods. Additionally, nanomaterials and food additives, such as flavors, antimicrobials, antioxidants, and colors, can be incorporated into edible films and coatings in order to extend their applications. Water-soluble hydrocolloids like polysaccharides usually impart better mechanical properties to edible films and coatings than do hydrophobic substances. They also are excellent barriers to oxygen and carbon dioxide. Recently, there has been much attention on carrageenan and alginate as sources of film-forming materials. Thus, this review highlights production and characteristics of these films. PMID- 26686141 TI - Interaction between chitosan-based clay nanocomposites and cellulose in a chemical pulp suspension. AB - Quaternized chitosan/organic montmorillonite (QCS/OMMT) nanocomposites were synthesized under microwave irradiation. XRD and TEM analyses confirmed that QCS intercalated into the interlayer of OMMT and clay layers distributed uniformly in QCS matrix. QCS/OMMT nanocomposites were used as retention and drainage-aid agents in pulp suspension, during which the interface behavior of positively charged QCS/OMMT nanocomposites on negatively charged cellulosic substrate and CaCO3 substrate was investigated. With the addition of QCS/OMMT nanocomposites, the particle size of cellulosic substrate increased, while the beating degree and the total residual carbohydrate concentration decreased. The results indicated that QCS/OMMT nanocomposite made a difference in paper making process through the charge patch interaction. Moreover, QCS/OMMT nanocomposites had a strong interaction with CaCO3, which was significant in fiber fines retention and paper production. When the mass ratio of QCS to OMMT was 8:1, the QCS/OMMT nanocomposite demonstrated the strongest retention and drainage-aid effect. PMID- 26686142 TI - Synthesis, optimization and structural characterization of a chitosan-glucose derivative obtained by the Maillard reaction. AB - Chitosan (Chit) was submitted to the Maillard reaction (MR) by co-heating a solution with glucose (Glc). Different reaction conditions as temperature (40, 60 and 80 degrees C), Glc concentration (0.5%, 1%, and 2%, w/v), and reaction time (72, 52 and 24h) were evaluated. Assessment of the reaction extent was monitored by measuring changes in UV absorbance, browning and fluorescence. Under the best conditions, 2% (w/v) of Chit, 2% (w/v) of Glc at 60 degrees C and 32 h of reaction time, a chitosan-glucose (Chit-Glc) derivative was purified and submitted to structural characterization to confirm its formation. Analysis of its molecular weight (MW) and the degree of substitution (DS) was carried out by HPLC-Size Exclusion Chromatography (SEC) and a colloid titration method, respectively. FT-IR and (1)H NMR were also used to analyze the functional groups and evaluate the introduction of Glc into the Chit molecule. According to our objectives, the results obtained in this work allowed to better understand the key parameters influencing the MR with Chit as well as to confirm the successful introduction of Glc into the Chit molecule obtaining a Chit-Glc derivative with a DS of 64.76 +/- 4.40% and a MW of 210.37 kDa. PMID- 26686143 TI - Carbohydrate polymer inspired silver nanoparticles for filaricidal and mosquitocidal activities: A comprehensive view. AB - The carbohydrate polymer inspired silver nanoparticles (AgNPs) are designed and synthesized through ultrasound assisted green process using unique combination of a biomolecule (tyrosine) and a natural polymer (starch). A comprehensive mechanistic study on the reactive oxygen species (ROS) mediated filaricidal (against Setaria cervi) and mosquitocidal (against second and fourth instar larvae of Culex quinquefasciatus) activities of AgNPs has been made for the first time for controlling filariasis by taking care of both filariid and its vector. The mechanism may help in formulating antifilarial drug based on carbohydrate polymer inspired AgNPs. The role of carbohydrate polymer in inspiring bioactivity of AgNPs has been looked into and its activities have been compared with the commercially available AgNPs. Cytotoxicity of AgNPs on macrophages of Wistar rat has been evaluated to ensure its selectivity towards filariid and larvae. PMID- 26686144 TI - Efficient Pb(II) removal using sodium alginate-carboxymethyl cellulose gel beads: Preparation, characterization, and adsorption mechanism. AB - Alginate-carboxymethyl cellulose (CMC) gel beads were prepared in this study using sodium alginate (SA) and sodium CMC through blending and cross-linking. The specific surface area and aperture of the prepared SA-CMC gel beads were tested. The SA-CMC structure was characterized and analyzed via infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Static adsorption experiment demonstrated that Pb(II) adsorption of SA-CMC exceeded 99% under the optimized conditions. In addition, experiments conducted under the same experimental conditions showed that the lead ion removal efficiency of SA-CMC was significantly higher than that of conventional adsorbents. The Pb(II) adsorption process of SA-CMC followed the Langmuir adsorption isotherm, and the dynamic adsorption model could be described through a pseudo-second-order rate equation. Pb(II) removal mechanisms of SA-CMC, including physical, chemical, and electrostatic adsorptions, were discussed based on microstructure analysis and adsorption kinetics. Chemical adsorption was the main adsorption method among these mechanisms. PMID- 26686145 TI - Study of interaction between water-soluble collagen and carboxymethyl cellulose in neutral aqueous solution. AB - The interactions of succinylated collagen (SC) and carboxymethyl cellulose (CMC) in neutral solutions (pH ~ 6.9) were investigated, which could provide information for the fields of tissue engineering and cosmetics. According to the results from viscometric measurements, the SC and CMC molecules were possibly compatible as CMC <= 50%. Ultrasensitive microcalorimetry reflected the increase in the values of transition temperature (Tm) and heat capacity change (DeltaCp) as CMC <= 50%, while both of them decreased as the CMC content further increased. Two-dimensional Fourier transform infrared spectroscopy analysis confirmed the hydrogen bonding and electrostatic interactions between SC and CMC, and the hydrogen bonding interaction played a key role as CMC <= 50%, while electrostatic interaction became predominant as more CMC was added. Atomic force morphology revealed the changes in the aggregation of SC induced by the addition of CMC. PMID- 26686146 TI - Extent of shielding by counterions determines the bactericidal activity of N,N,N trimethyl chitosan salts. AB - In this study, we show that the bactericidal activity of quaternized chitosans (TMCs) with sulfate, acetate, and halide counterions against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) correlates with the "availability" of N-quaternized groups [-(+)N(CH3)3] in the TMCs backbones. N,N,N-trimethyl chitosan sulfate (TMCS) and N,N,N-trimethyl chitosan acetate (TMCAc) displayed the highest activities, probably due to their delocalized pi system. Among TMCs with halide counterions, activity was higher for N,N,N-trimethyl chitosan chloride (TMCCl), whereas N,N,N-trimethyl chitosan iodide (TMCI) and N,N,N trimethyl chitosan bromide (TMCBr) exhibited lower, similar values to each other. This is consistent with the shielding of -(+)N(CH3)3 groups inferred from chemical shifts for halide counterions in (1)HNMR spectra. We also demonstrate that TMCs with distinct bactericidal activities can be classified according to their vibrational spectra using principal component analysis. Taken together, these physicochemical characterization approaches represent a predictive tool for the bactericidal activity of chitosan derivatives. PMID- 26686147 TI - Characterization of un-plasticized and propylene carbonate plasticized carboxymethyl cellulose doped ammonium chloride solid biopolymer electrolytes. AB - Two solid biopolymer electrolytes (SBEs) systems of carboxymethyl cellulose doped ammonium chloride (CMC-AC) and propylene carbonate plasticized (CMC-AC-PC) were prepared via solution casting technique. The ionic conductivity of SBEs were analyzed using electrical impedance spectroscopy (EIS) in the frequency range of 50 Hz-1 MHz at ambient temperature (303K). The highest ionic conductivity of CMC AC SBE is 1.43 * 10(-3)S/cm for 16 wt.% of AC while the highest conductivity of plasticized SBE system is 1.01 * 10(-2)S/cm when added with 8 wt.% of PC. TGA/DSC showed that the addition of PC had increased the decomposition temperature compared of CMC-AC SBE. Fourier transform infrared (FTIR) spectra showed the occurrence of complexation between the SBE components and it is proved successfully executed by Gaussian software. X-ray diffraction (XRD) indicated that amorphous nature of SBEs. It is believed that the PC is one of the most promising plasticizer to enhance the ionic conductivity and performance for SBE system. PMID- 26686148 TI - Alkynyl-functionalization of hydroxypropyl cellulose and thermoresponsive hydrogel thereof prepared with P(NIPAAm-co-HEMAPCL). AB - A ternary system thermoresponsive hydrogel, poly(N-isopropylacrylamide-co hydroxyethyl methylacrylate polycaprolactone)/hydroxypropyl cellulose (or P(NIPAAm-co-HEMAPCL)/HPC), was prepared via "alkynyl/azide" click chemistry between the azide modified graft copolymer P(NIPAAm-co-HEMAPCL-N3) and the alkynyl modified HPC (or alkynyl-HPC). The structures of P(NIPAAm-co-HEMAPCL-N3) and alkynyl-HPC were characterized by (1)H NMR, SEC and FT-IR, and the results demonstrated that the mole ratio of the alkynyl and azide functional groups, and the feed ratios of HPC, PCL, and PNIPAAm could be easily adjusted. The incorporation of PCL and HPC dramatically enhanced the compression modulus of the P(NIPAAm-co-HEMAPCL)/HPC hydrogel, which ranged from 500 to 1000 g/cm(2). Due to the immiscibility of HPC and PCL, a heterogeneous and semicontinuous structure was observed via SEM. The incorporation of HPC accelerated the water absorption rate and enhanced the hydrogel's ability to shed water. The swelling-deswelling and compressive properties could also be adjusted by changing the feeding ratio. The hydrogel exhibited reversible swelling-deswelling behavior after three "swelling-deswelling" cycles. PMID- 26686149 TI - Purification and characterization of exopolysaccharide bioflocculant produced by heavy metal resistant Achromobacter xylosoxidans. AB - Optimization of process parameters enhanced bioflocculating activity of 'Achromobacter xylosoxidans strain TERI L1' from 75% to 83.3% in absence of heavy metals, which decreased to 73% in presence of multi-metals. 'TERI L1' could adsorb 90% of multi-metals when grown in presence of 1250 mg L(-1) Zn, 2 mg L(-1) Cd, 30 mg L(-1) Pb, 200 mg L(-1) Ni and 90 mg L(-1) Cu and could adsorb 1100 mg L(-1) of Pb when grown in presence of 1500 ppm lead nitrate. The bioflocculant was purified and characterized. Bioflocculant yield was 5 g L(-1). Fourier transform infrared spectrum indicated presence of carboxyl, hydroxyl, amino groups, typical of glycoprotein. Spectroscopic analysis of bioflocculant by nuclear magnetic resonance revealed that it is a glycoprotein. LC-MS analysis confirmed the bioflocculant as a carbohydrate hetero polymer. Bioflocculant was composed of 75% total sugar with 72.9% neutral sugar and 11.5% protein. Scanning Electron Micrography revealed effective flocculation of kaolin clay by purified exopolysaccharide bioflocculant. PMID- 26686150 TI - Biodegradable polymer blends based on corn starch and thermoplastic chitosan processed by extrusion. AB - Blends of thermoplastic cornstarch (TPS) and chitosan (TPC) were obtained by melt extrusion. The effect of TPC incorporation in TPS matrix and polymer interaction on morphology and thermal and mechanical properties were investigated. Possible interactions between the starch molecules and thermoplastic chitosan were assessed by XRD and FTIR techniques. Scanning Electron Microscopy (SEM) analyses showed a homogeneous fracture surface without the presence of starch granules or chitosan aggregates. Although the incorporation of thermoplastic chitosan caused a decrease in both tensile strength and stiffness, films with better extensibility and thermal stability were produced. PMID- 26686151 TI - Centrifugally spun starch-based fibers from amylopectin rich starches. AB - Centrifugal spinning and electrospinning have proved to be effective techniques for fabricating micro-to-nanofibers. However, starches of amylopectin content above 65% cannot be fabricated to fiber by electrospinning. This paper is focus on the centrifugal spinnability of amylopectin rich starches. We investigated the amylopectin content of starches by Dual-wavelength colorimetry, studied the rheological properties of starch dopes to determine entanglement concentration (ce) by rotary rheometer. Results indicated that amylopectin rich native corn and potato starches, which with amylopectin content higher than 65%, were suitable for centrifugal spinning to micro-to-nanofibers. Additionally, starch-based fibers were successfully fabricated from the amylose rich corn starch as well. Rheological studies showed that the entanglement concentration (ce) of starch solution was crucial for successful centrifugal spinning. PMID- 26686152 TI - Unit and internal chain profile of African rice (Oryza glaberrima) amylopectin. AB - High-performance anion-exchange chromatography was used to study the unit chain profiles of amylopectins and their phi,beta-limit dextrins from two African rice (Oryza glaberrima) accessions-TOG 12440 and IRGC 103759. The samples were compared with two Asian rice (Oryza sativa) samples (cv Koshihikari and cv WITA 4) and one O. sativa * O. glaberrima cross (NERICA 4). The ratio of short:long chains ranged between 12.1 and 13.8, and the ratio of A:B-chains was ~ 1.0 in all samples. A significant difference was observed in the distribution of internal chains with regards to the proportion of short "fingerprint" B-chains (Bfp chains), which in the phi,beta-limit dextrins have a degree of polymerization (DP) 3-7. The African rice starches and NERICA 4 had higher levels of Bfp-chains, but the major group of short B-chains (DP 8-25) was similar to that of the Asian rice samples. The average chain length (CL), internal chain length (ICL), and total internal chain length (TICL) were similar in all samples. However, the external chain length (ECL) was longer in the African rice samples and NERICA 4. ECL correlated positively and significantly (p<0.05) with gelatinization transition temperatures and enthalpy suggesting differences between the two rice types in cooking properties. PMID- 26686153 TI - Ultrasound extraction of polysaccharides from mulberry leaves and their effect on enhancing antioxidant activity. AB - A Box-Behnken design (BBD) was applied to optimize the ultrasound-assisted extraction of polysaccharides from mulberry leaves. Under the optimum conditions of an extraction temperature of 57 degrees C, an extraction time of 80 min and a liquid/solid ratio of 53 mL/g, the mulberry leaf polysaccharide (MLP) yield was 6.92 +/- 0.29%. Then, three fractions of MLPs were obtained by deproteinization, dialysis and decolorization. The carbohydrate content, FT-IR spectrum and monosaccharide composition of the MLPs were also investigated. The antioxidant activities of the three fractions were compared, and the results indicated that the antioxidant activities decreased with the increasing MLP purity. Therefore, highly concentrated MLPs were shown to have very little antioxidant activity. After quercetin (10 MUg/mL) was added, the antioxidant activities were improved significantly. This result showed that MLPs and quercetin have a synergistic effect on the antioxidant activity. Although the MLPs have very little antioxidant activity alone, they greatly enhance the antioxidant activity of flavonoids. Thus, MLPs can be used as an antioxidant activity enhancer in the food industry. PMID- 26686154 TI - On the percolation of alginate/calcium systems at low concentrations. AB - The sol-to-gel transition of an alginate rich in beta-d-mannuronic acid residues and at a concentration of 0.1% w/v in 15 mM NaCl in the presence of calcium ions of 0 to 3.5mM was studied with dynamic light scattering. The dynamics of the different systems added further insight into the alginate gel forming mechanisms. Below a Ca(2+) concentration of 0.7 mM, the build-up of small aggregates could be verified. Moreover, at a critical concentration, close to 0.9 mM Ca(2+), a percolated, non-ergodic network started to form from some of these aggregates, with smaller aggregates still diffusing in the network. The system displayed strong non-ergodicy at high Ca(2+) concentrations with a non-ergodicity parameter that appeared to form discontinuously from near zero to a clearly non-zero value at the critical Ca(2+) concentration. PMID- 26686155 TI - Transformation of crystalline starch nanoparticles into highly luminescent carbon nanodots: Toxicity studies and their applications. AB - Being abundant in many tropical part of the world, Dioscorea sp. as food is limited due to its toxicity. However polysaccharides derive from these tubers could be important for other applications. Here we developed a Highly Luminescent Carbon Nanodots (C-dots) via acid hydrolysis of Gadong starch (GS). The hydrolysis rate of GS increased from 49% to 86% within 7 days while the X-ray diffraction showed the native GS particle is a C-crystalline type. The GS particles were either round or oval with diameters ranging from 50-90 nm. Further acid dehydration and surface oxidation reduced the size of GS nanoparticles to 6 25 nm. The C-dots produced a fluorescent emission at wavelength 441 nm. Toxicity tests demonstrate that zebrafish embryo were able to tolerate the C-dots for 48 h after exposure. This study has successfully demonstrated a novel approach of converting GS into excellent fluorescent C-dot. PMID- 26686156 TI - Hemocompatible curcumin-dextran micelles as pH sensitive pro-drugs for enhanced therapeutic efficacy in cancer cells. AB - Curcumin, a component in spice turmeric, is renowned to possess anti-cancer therapeutic potential. However, low aqueous solubility and instability of curcumin which subsequently affects its bioavailability pose as major impediments in its translation to clinical application. In this regard, we focused on conjugating hydrophobic curcumin to the hydrophilic backbone of dextran via succinic acid spacer to design a pro-drug. The structural confirmation of the conjugates was carried out using FTIR and (1)H NMR spectroscopy. Critical micelle measurement affirmed the micelle formation of the pro-drug in aqueous media. The size distribution and zeta potential of the curcumin-dextran (Cur-Dex) micelles were determined using dynamic light scattering technique. The micellar architecture bestowed curcumin negligible susceptibility to degradation under physiological conditions along with enhanced aqueous solubility. Biocompatibility of the micelles was proved by the blood component aggregation and plasma protein interaction studies. In vitro release studies demonstrated the pH sensitivity release of curcumin which is conducive to the tumour micro environment. Profound cytotoxic effects of Cur-Dex micelles in C6 glioma cells were observed from MTT and Live/Dead assay experiments. Moreover, enhanced cellular internalization of the Cur-Dex micelles compared to free curcumin in the cancer cells was revealed by fluorescence microscopy. Our study focuses on the feasibility of Cur-Dex micelles to be extrapolated as promising candidates for safe and efficient cancer therapy. PMID- 26686157 TI - Biological properties of dialdehyde carboxymethyl cellulose crosslinked gelatin PEG composite hydrogel fibers for wound dressings. AB - Gelatin-based composite hydrogel fibers were prepared by gel-spinning with PEG6000 as the modifier. Dialdehyde carboxymethyl cellulose (DCMC), as an ideal crosslinking reagent for protein, was used to fix the composite hydrogel fibers. Then the biological properties of the hydrogel fibers for wound dressings were evaluated. The results indicate that the hydrogen bond interactions and CN linkages between gelatin and DCMC can be formed. The addition of DCMC can efficiently improve the mechanical properties, enzymatic stability and blood compatibility of the hydrogel fibers. Crosslinking with DCMC can reduce the degree of swelling of the hydrogel fibers, which is beneficial for hydrogel fibers to avoid undesired reduction in mechanical properties. Moreover, the composite hydrogel fibers present three-dimensional structure, porous networks and low cytotoxicity. The study suggests that DCMC is an effective crosslinking reagent for biomaterials fixation. The developed composite hydrogel fibers can be well-suited for biomedical applications such as wound dressings. PMID- 26686158 TI - Property tuning of poly(lactic acid)/cellulose bio-composites through blending with modified ethylene-vinyl acetate copolymer. AB - The effect of addition of an ethylene-vinyl acetate copolymer modified with glycidyl methacrylate (EVA-GMA) on the structure and properties of poly(lactic acid) (PLA) composites with cellulose micro fibres (CF) was investigated. Binary (PLA/CF) and ternary (PLA/EVA-GMA/CF) composites obtained by melt mixing in Brabender mixer were analysed by SEM, POM, WAXS, DSC, TGA and tensile tests. The miscibility and morphology of PLA/EVA-GMA blends were first examined as a function of composition: a large rise of PLA spherulite growth rate in the blends was discovered with increasing the EVA-GMA content (0-30 wt%) in the isothermal crystallization both from the melt and the solid state. PLA/EVA-GMA/CF ternary composites displayed improved adhesion and dispersion of fibres into the matrix as compared to PLA/CF system. Marked changes of thermodynamic and tensile parameters, as elastic modulus, strength and elongation at break were observed for the composites, depending on blend composition, polymer miscibility and fibre matrix chemical interactions at the interface. PMID- 26686159 TI - Pysicochemical properties of Tibetan hull-less barley starch. AB - Objectives of this study were to (1) determine the starch physicochemical properties of two commercial Tibetan hull-less barley varieties, Beiqing (BQ) and Kangqing (KQ); and (2) understand the relationship between unique properties of the starches, their structures, and impacts of growing conditions. The BQ barleys were grown at a location with lower temperature and less rainfall compared with the KQ barleys. The BQ starches showed significantly lower onset-gelatinization temperature (54.1-54.9 degrees C), larger gelatinization-temperature range (9.4 10.6 degrees C), and higher peak-viscosities (138.9-153.9RVU) than the KQ starches (55.1-56.1 degrees C, 7.4-8.8 degrees C, and 63.4-64.7RVU, respectively). After a treatment with 2% sodium-dodecyl-sulphate solution, the KQ starches showed substantially greater increases in peak viscosities than the BQ starches. Annealing of starch and enhanced amylose-lipid complex formation, resulting from higher growing temperature during the development of the KQ starches, likely contributed to the differences in thermal and pasting properties between the BQ and KQ starches. PMID- 26686160 TI - Positively and negatively surface-charged chondroitin sulfate-trimethylchitosan nanoparticles as protein carriers. AB - Positively and negatively surface-charged nanoparticles (NPs) were prepared with chondroitin sulfate (ChS) and trimethylchitosan (TMC). NP size, surface charge, formation yield, and water content were investigated as a function of weight ratio and concentration. Size and zeta potential were controlled by varying the ChS/TMC mass ratio. FTIR spectra revealed interactions among composite NP constituents. TEM images showed that the NPs were nearly spherical, with an average size of ~ 300 nm. Encapsulation efficiency increased in positively charged NPs with increases in fluorescein isothiocyanate-bovine serum albumin concentration. Negatively charged NPs had only 10-20% encapsulation efficiency. The release profile, release kinetics and mechanism of positively charged ChS-TMC NPs were studied in vitro. NP cytocompatibility and uptake were verified ex vivo. Both types of NPs were taken up and retained in cells. A549 cells took up more positively charged (49.4%) than negatively charged (35.5%) NPs. PMID- 26686161 TI - Extraction, characterization and antioxidant activity of mycelial polysaccharides from Paecilomyces hepiali HN1. AB - Optimization of extraction, characterization and antioxidant activity of mycelial polysaccharides from Paecilomyces hepiali HN1 (PHMPs) were investigated. As results, the optimal parameters for extraction of PHMPs were obtained by a Box Behnken design as follows: extraction temperature 92 degrees C, extracting time 190 min and ratio of water to material 43 mL/g. The analysis of monosaccharide composition by high performance liquid chromatography (HPLC) revealed that PHMPs was composed of mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose and arabinose in molar ratio of 46.07:0.59:2.25:1.29:1.42:18.82:26.17:1.13:2.26, respectively. Furthermore, it was demonstrated that PHMPs had a significant protective effect against oxidative stress induced by d-galactose in mice, as evident by higher activities of superoxide dismutase, catalase, glutathione peroxidase and level of total antioxidant capacity, as well as lower levels of malondialdehyde in serums and livers compared to the d-galactose-treated group. These results suggested that PHMPs could be explored as promising natural antioxidant. PMID- 26686162 TI - Hydrophobic modification of cotton fabric with octadecylamine via laccase/TEMPO mediated grafting. AB - Hydrophobic cotton fabrics were prepared by grafting octadecylamine (ODA) onto cotton fiber surfaces via the laccase/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) treatment. The cotton fibers were oxidized by laccase/TEMPO to introduce aldehyde groups, which reacted with the amino groups of ODA to form Schiff base. First, ODA was coupled to glucan, used as a model compound of cellulose. The results of FT-IR and MALDI-TOF mass spectroscopy prove the formation of a Schiff base between ODA and glucan. Moreover, the existence of ODA in the grafted cotton fibers was verified by ATR-FTIR, elemental analysis, X-ray photoelectron spectroscopy. Finally, the hydrophobicity of the ODA-grafted cotton fabrics was estimated. The surface hydrophobicity of the cotton fabrics increased after the enzymatic grafting reaction. PMID- 26686163 TI - Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses. AB - The acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of BC were studied. Cytotoxicity of BC was evaluated in cultured C3A hepatoma cells (HepG2/C3A) using a lactate dehydrogenase (LDH) activity assay. Acute toxicity was tested in adults Wistar rats treated with a single dose of BC. The genotoxicity of BC was evaluated in vivo by the micronucleus assay. BC (0.33-170 MUg/mL) added to C3A cell culture medium caused no elevation in LDH release over the background level recorded in untreated cell wells. The treatment with the BC in a single oral dose (2000 mg/kg body weight) caused no deaths or signs of toxicity. BC attenuated CP-induced and inhibition the incidence of MNPCE (female: 46.94%; male: 22.7%) and increased the ratio of PCE/NCE (female: 46.10%; male: 35.25%). There was no alteration in the LDH release in the wells where C3A cells were treated with increasing concentrations of BC compared to the wells where the cells received the cell culture medium only (background of approximately 20% cell death), indicated that in the dose range tested BC was not cytotoxic. BC was not cytotoxic, genotoxic or acutely toxic. BC attenuated CP-induced genotoxic and myelotoxic effects. PMID- 26686164 TI - Mutan: A mixed linkage alpha-[(1,3)- and (1,6)]-d-glucan from Streptococcus mutans, that induces osteoclast differentiation and promotes alveolar bone loss. AB - Mutan is an extracellular polysaccharide of Streptococcus mutans (S. mutans) that consists of alpha-(1,3)-linked glucose residues in main chains and alpha-(1,6) bonds in side chains. In the present study, mutan was isolated from S. mutans, and its structural characteristics were determined using Fourier-transform infrared spectroscopy (FT-IR) and (13)C nuclear magnetic resonance (NMR) spectroscopy. The effects of mutan on RANKL-induced osteoclast differentiation in RAW 264.7 cells were examined. Furthermore, microCT and morphometric analyses were used to determine the contribution of mutan to alveolar bone loss in the maxilla of a rat periodontitis model. Mutan increased (more than 2-fold) RANKL induced osteoclast differentiation in a dose-dependent manner. Mutan also enhanced the alveolar bone loss in the rat maxilla 2.3-fold. In mutan-treated rats, the bone mineral density, bone volume, trabecular number, and trabecular thickness decreased, whereas trabecular separation significantly increased. In addition, mutan and lipopolysaccharide (LPS) induced similar microarray profiles in RAW 264.7 cells. A total of 43 genes related to osteoclastogenesis were differentially expressed after either mutan or LPS treatment. Five-fold increases in the expression of several genes, including IL-1beta, IL-1alpha, IL-6, and chemokine ligands, were observed in mutan-treated RAW 264.7 cells. These results suggest a molecular mechanism for the inflammation induced by S. mutans during the establishment of periodontal disease. PMID- 26686165 TI - Structure identification of a polysaccharide purified from litchi (Litchi chinensis Sonn.) pulp. AB - As a health-beneficial fruit, litchi is widely accepted by people in subtropical and tropical regions. However, the critical chemicals responsible for the health benefits are not clear yet. As a large amount of polysaccharides are present in litchi, they might play an important role in the health benefits. In this work, the main water-soluble polysaccharide (LPPBa) was purified from litchi pulp. The chemical structure was characterized as arabinogalactan by gas chromatography and nuclear magnetic resonance spectrometry (NMR). NMR data revealed the glycosidic linkages and their locations in backbone and branches. The precise structure was putatively identified as below, and it was different to those commonly occurred arabinogalactans. The molecular weight was determined to be 2.4 * 10(6)Da by gel permeation chromatography. PMID- 26686166 TI - Evaluation of physicochemical and biological properties of chitosan/poly (vinyl alcohol) polymer blend membranes and their correlation for Vero cell growth. AB - The blend membranes with varying weight ratios of chitosan/poly (vinyl alcohol) (CS/PVA) (1:0, 1:1, 1:2.5, 1.5:1, 1.5: 2.5) were prepared using solvent casting method and were evaluated for their potential application in single-use membrane bioreactors (MBRs). The physicochemical properties of the prepared membranes were investigated for chemical interactions (FTIR), surface morphology (SEM), water uptake, protein sorption (qe), ammonia sorption and growth kinetics of Vero cells. CS/PVA blend membrane having weight ratio of 1.5:1 had shown enhanced membrane flexibility, reduced water uptake, less protein sorption and no ammonium sorption compared to CS membrane. This blend membrane also showed comparatively enhanced higher specific growth rate (0.82/day) of Vero cells. Improved physicochemical properties and growth kinetics obtrude CS/PVA (1.5:1) as a potential surface for adhesion and proliferation with possible application in single use membrane bioreactors. Additionally, new insight explaining correlation between water holding (%) of CS/PVA (1.5:1) blend membrane and doubling time (td) of Vero cells is proposed. PMID- 26686167 TI - Highly biocompatible collagen-Delonix regia seed polysaccharide hybrid scaffolds for antimicrobial wound dressing. AB - Biomaterials based entirely on biological resources are ideal for tissue engineering applications. Here we report the preparation of hybrid collagen scaffolds comprising gulmohar seed polysaccharide (GSP) and cinnamon bark extract as cross-linking agent. (1)H NMR spectrum of GSP confirms the presence of galactose and mannose in the ratio of 1:1.54, which was further corroborated using FT-IR. The hybrid scaffolds show better enzyme and thermal stability in contrast to pure collagen scaffold probably due to weak interactions from GSP and covalent interaction through cinnamaldehyde. Gas permeability and scanning electron microscopic analysis show that the porosity of the hybrid scaffolds is slightly reduced with the increase in the concentration of GSP. The infrared and circular dichroic spectral studies show that the secondary structure of the collagen did not change after the interaction with GSP and cinnamaldehyde. The hybrid scaffolds stabilized with cinnamaldehyde show good antimicrobial activity against the common multi-drug resistant wound pathogens. These results suggest that the prepared hybrid scaffolds have great potential for antimicrobial wound dressing applications. PMID- 26686168 TI - Effects of ionic conduction on hydrothermal hydrolysis of corn starch and crystalline cellulose induced by microwave irradiation. AB - This study investigated the effects of ionic conduction of electrolytes under microwave field to facilitate hydrothermal hydrolysis of corn starch and crystalline cellulose (Avicel), typical model biomass substrates. Addition of 0.1M NaCl was effective to improve reducing sugar yield by 1.61-fold at unit energy (kJ) level. Although Avicel cellulose was highly recalcitrant to hydrothermal hydrolysis, addition of 0.1M MgCl2 improved reducing sugar yield by 6.94-fold at unit energy (kJ). Dielectric measurement of the mixture of corn starch/water/electrolyte revealed that ionic conduction of electrolytes were strongly involved in facilitating hydrothermal hydrolysis of polysaccharides. PMID- 26686169 TI - Synthesis of carboxymethyl chitin in aqueous solution and its thermo- and pH sensitive behaviors. AB - Homogenous modification of natural chitin offers the advantage of fair structure control. In this work, novel carboxymethyl chitins (CMCHs) with broad range of degree of substitution (DS: 0.035 to 0.74), high degree of acetylation (DA) and little de-polymerization were synthesized homogeneously in aqueous NaOH/urea solution. The simultaneous determination of DA, DS and carboxymethylation fraction at C3 and C6 for these CMCHs was achieved by proton NMR in acidic deuterated aqueous solution for the first time. Due to the good homogeneity, the prepared CMCH-4 with lower DS of carboxymethylation exhibited, for the first time to our knowledge, dual thermo- and pH-sensitive properties. The nontoxic thermo sensitive polymer systems gel at body temperature (37 degrees C) in physiological condition, which is very useful as injectable hydrogels for drug delivery and tissue engineering. PMID- 26686170 TI - Isolation and characterization of cellulose nanofibers from culinary banana peel using high-intensity ultrasonication combined with chemical treatment. AB - In the present study, culinary banana peel was explored as a source of raw material for production of cellulose nanofibers (CNFs). For isolation of CNFs, first the peel flour was subjected to different chemical treatments to eliminate non-cellulosic compounds. The obtained chemically treated cellulose fibers were then mechanically tailored and separated into nanofibers using high-intensity ultrasonication at different output power ranging from 0 to 1000 W. The presences of nanofibers in all samples were confirmed by TEM. Increasing output power of ultrasonication reduced size of CNFs and generated more thinner and needle-like structure. SEM, FT-IR and XRD results indicated chemical treatment employed was effective in removing compounds other than cellulose fibers. Thermal analyses evinced the developed CNFs enhanced thermal properties which serve the purpose as an effective reinforcing material to be used as bionanocomposites. Hence, the production of CNFs from this underutilized agro-waste has potential application in commercial field that can add high value to culinary banana. PMID- 26686171 TI - Effect of chito-oligosaccharides over human faecal microbiota during fermentation in batch cultures. AB - Chitosan with high number of deacetylated units, its reacetylated derivative and COS obtained through an enzymatic treatment with chitosanase were tested in pH controlled batch cultures to investigate the ability of the human faecal microbiota to utilise them. Chitosan derivatives with high number of deacetylated units decreased the bacterial populations: Bifidobacterium spp., Eubacterium rectale/Clostridium coccoides, C. Histolyticum and Bacteroides/Prevotella. On the other hand, chitosan derivatives with high content of acetylated residues maintained the tested bacterial groups and could increase Lactobacillus/Enterococcus. Regarding short chain fatty acids (SCFA), only low Mw COS increased the production in similar levels than fructo-oligossacharides (FOS). The acetylated chitosans and their COS do not appear as potential prebiotics but did not affect negatively the faecal microbiota, while derivatives with high number of deacetylated units could induce a colonic microbiota imbalance. PMID- 26686172 TI - Novel functional polysaccharides from Radix Polygoni Multiflori water extracted residue: Preliminary characterization and immunomodulatory activity. AB - The alkali-extractable polysaccharides (APMPs) were isolated from the water extracted residues of Radix Polygoni Multiflori, and further purified by DEAE-52 cellulose and Sephadex G-100 column chromatography to obtain a homogeneous polysaccharide (APMP-2) with molecular weights of 7724.8 Da. HPLC chromatography analysis identified that APMP-2 was a heteropolysaccharides and mainly composed of Galactose and Xylose with a molar ratio of 4.31: 1.06. It was shown that both APMP and APMP-2 were of activation effects on splenocytes and peritoneal macrophages, and also significantly restore the proliferation rate, phagocytic index and cytokine (IL-2 and TNF-alpha) production level of 5-FU-treated splenocytes/peritoneal macrophages in a dosage-dependent manner. The results suggested that polysaccharides presented in Radix Polygoni Multiflori water extracted residues possessed immunomodulatory activity and could be used as potential immunomodulators, and this finding could be a reference for the utilization of Radix Polygoni Multiflori water extracted residues. PMID- 26686173 TI - Preparation, characterization and feasibility study of dialdehyde carboxymethyl cellulose as a novel crosslinking reagent. AB - The natural biopolymers usually need to be chemically modified by crosslinking reagents to improve their mechanical properties. In the present research, the feasibility of using the dialdehyde carboxymethyl cellulose (DCMC) as a crosslinking reagent was systematically studied. DCMC was prepared by oxidizing carboxymethyl cellulose using sodium periodate. The formation of dialdehyde groups was confirmed by FTIR and the degree of oxidation was determined. The biocompatibility of DCMC was investigated by evaluating its cytotoxicity to L929 fibroblasts and histocompatibility in rat model via intramuscular and subcutaneous injection. DCMC-crosslinked carboxymethyl chitosan (DCMC-CMCTS) was prepared and characterized using the glutaraldehyde-crosslinked CMCTS (GA-CMCTS) as control. The result demonstrated that DCMC was non-cytotoxic, biodegradable and biocompatible. The DCMC-CMCTS displayed significantly better thermostability, swelling capacity and cyto-compatibility compared with GA-CMCTS. Our data provided experimental basis for the future application of DCMC as a novel crosslinking reagent. PMID- 26686174 TI - Cellulose aerogels prepared from an aqueous zinc chloride salt hydrate melt. AB - Monolithic cellulose aerogels are prepared using a salt hydrate melt based on cheap zinc chloride tetrahydrate (ZnCl2.4H2O) that can be washed out of the wet gel-body by using common solvents such as water, ethanol, isopropanol or acetone. Cellulose aerogels with concentrations of 1-5 wt.% cellulose were produced. These aerogels are characterized with respect to shrinkage, density and surface area as well as mechanical properties and micro-structure via SEM. Cellulose aerogels regenerated in acetone show a specific surface area of around 340 m(2)g(-1) being 60% higher than those regenerated in water. The onset of irreversible plastic deformation under compressive load is around 0.8 MPa for acetone-regenerated aerogels and thus a factor of two larger compared to ethanol regenerated ones. The Young's modulus depends almost linearly on the cellulose concentration which is observed for all regenerative fluids with the exception of water. The results achieved are presented in light of the polarity and ability of solvation of ZnCl2.4H2O in the regenerative fluids used. PMID- 26686175 TI - Controlled methyl-esterification of pectin catalyzed by cation exchange resin. AB - This study developed a new method to methyl-esterify pectin using a cation exchange resin. Homogalacturonan (HG)-type pectin (WGPA-3-HG) and rhamnogalacturonan (RG)-I-type pectin (AHP-RG) obtained from the roots of Panax ginseng and sunflower heads, respectively, were used as models. Compared to commonly used methyl-esterification methods that use either methyl iodide or acidified methanol, the developed method can methyl-esterify both HG- and RG-I type pectins without degrading their structures via beta-elimination or acid hydrolysis. In addition, by modifying reaction conditions, including the mass ratio of resin to pectin, reaction time, and temperature, the degree of esterification can be controlled. Moreover, the resin and methanol can be recycled to conserve resources, lower costs, and reduce environmental pollution. This new methodology will be highly useful for industrial esterification of pectin. PMID- 26686176 TI - Esterification of potato starch by a biocatalysed reaction in an ionic liquid. AB - In this study, potato starch was esterified with oleic acid, using 1-butyl-3 methylimidazolium chloride as a reaction medium and an immobilised lipase from Thermomyces lanuginosus as a catalyst. The degree of substitution (DS) of the products was determined by the volumetric method; and the best esterified product (with the highest DS) was determined by an elemental analysis. The effect of the reaction parameters on the DS, such as the time and the temperature, were also studied. The product with the highest DS (0.22) was found in the reaction carried out at 60 degrees C for 4h. Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses confirmed the esterification of the potato starch. Furthermore, the results of X-ray diffraction (XRD) and a scanning electron microscopy (SEM) revealed that the crystallinity and the morphology of the native potato starch was slightly changed during its partial gelatinisation in the ionic liquid, and was completely destroyed as a result of the formation of the esters. The thermal stability of the starch oleate decreased, when compared to the unmodified starch, as was indicated by a thermal gravimetric analysis (TGA). PMID- 26686177 TI - Long-term degradation study of hyaluronic acid in aqueous solutions without protection against microorganisms. AB - The degradation of hyaluronan (HA) of different molecular weights (Mw 14.3, 267.2 and 1160.6 kDa, measured for fresh solutions, before degradation) was studied in aqueous solutions by SEC-MALLS determination of molecular mass, polydispersity and conformation parameters. The solutions were stored either at laboratory or refrigerator temperatures for two months. After this period the weight average molecular weight decreased by 90% for 14.3 kDa, 95% for 267.2 kDa and 71% for 1160.6 kDa hyaluronan (room temperature) or 5.6% for 14.3 kDa, 6.2% for 267.2 kDa and 7.7% for 1160.6 kDa hyaluronan (refrigerator temperature). The hyaluronan aqueous solutions studied did not contain sodium azide or other protectants against microorganisms, because the aim of our study was to assess the degradation in solutions to be used in medicine or cosmetics (without any compounds that are poisonous or toxic for the human body). The solvent used to prepare the samples was pure water. The polydispersity of all the samples remained unaltered during the entire degradation at both temperatures. This indicates a non-random mechanism of degradation. PMID- 26686178 TI - Novel glycol chitosan-based polymeric gene carrier synthesized by a Michael addition reaction with low molecular weight polyethylenimine. AB - A glycol chitosan-based polymer that spontaneously assembles with plasmid DNA into nanorods was evaluated as a non-viral vector for gene delivery. Glycol chitosan-methyl acrylate-polyethylenimine (GMP) was synthesized by grafting polyethylenimine onto glycol chitosan via amidation after Michael addition using methyl acrylate. Gel retardation and PicoGreen assay experiments showed complete complex formation with plasmid DNA. GMP/pDNA complexes were characterized using biophysical techniques and were found to be positively charged rod-shape structures with widths in the nanometer scale and lengths in the micrometer scale. Transfection efficiency and cytotoxicity of GMP polymer was evaluated in human epithelial ovary carcinoma (HeLa) cells, human embryonic kidney 293 (HEK293) cells, and human hepatocellular liver carcinoma (HepG2) cells, in comparison to high molecular weight polyethylenimine, a commonly used transfection reagent. Intracellular polymer uptake was compared and confirmed by confocal microscopy. The results demonstrate that GMP, a hybrid polymer of glycol chitosan grafted with branched polyethylenimine, may serve as a promising vehicle for efficient gene delivery. PMID- 26686179 TI - Structure of beta-chitin from Berryteuthis magister and its transformation during whisker preparation and polymerization filling. AB - Models for the structures of the beta-chitin-protein complex of native and deproteinized squid pen (Berryteuthis magister) based on SAXS and WAXS data are proposed. Chitin fibrils of 25 A in diameter and persistence length of 1200 A are immersed in protein matrix. Average distance between fibrils is 42 A. Deproteinization of the squid pen led to disappearance of the lateral fibril order stabilized by the protein matrix of the native sample. Swelling in water and acrylic acid resulted in an increase in the chitin 010 D-spacing to 14 and 18 A, respectively. A preparation routine for individual chitin nanofibers of few microns in length and with diameter of 40-60 A has been developed. During exfoliation of the chitin in acrylic acid the degree of acetylation does not change. Chitin-based nanocomposites can be prepared by polymerization of acrylic acid in swelled deproteinized samples which takes place mainly in the interfibrillar space of beta-chitin mainly. PMID- 26686180 TI - Cellulose acetate fibers prepared from different raw materials with rapid synthesis method. AB - Transesterification is a mild process to prepare cellulose acetate (CA) as compared with the traditional method. In this study, CA fibers were produced from six cellulose raw materials based on a simple and rapid transesterification method. The properties of the CA solutions and the obtained CA fibers were investigated in detail. Results showed that all of the cellulose raw materials were esterified within 15 min, and spinning dopes could be obtained by concentrating the CA solutions via vacuum distillation. The XRD, FT-IR, (1)H, (13)C and HSQC NMR analysis confirmed the successful synthesis of CA. The degree of substitution (DS) of the obtained CA was significantly affected by the degree of polymerization (DP) of cellulose raw materials, which further influenced the viscosity of CA solutions as well as the structural, thermal and mechanical properties of the CA fibers. PMID- 26686182 TI - Purification and characterization of a novel polysaccharide-peptide complex from Clinacanthus nutans Lindau leaves. AB - A novel polysaccharide-peptide complex CNP-1-2 with molecular weight of 9.17 * 10(4) Da was obtained from Clinacanthus nutans Lindau leaves by hot water extraction, ethanol precipitation, and purification with Superdex 200 and DEAE Sepharose Fast Flow column chromatography. CNP-1-2 exhibited the highest growth inhibitory effect on human gastric cancer cells SGC-7901 with inhibition ratio of 92.34% and stimulated activation of macrophages with NO secretion level of 47.53 MUmol/L among the polysaccharide fractions. CNP-1-2 comprised approximately 87.25% carbohydrate and 9.37% protein. Monosaccharide analysis suggested that CNP 1-2 was composed of L-rhamnose, l-arabinose, D-mannose, D-glucose and D-galactose with a molar ratio of 1.30:1.00:2.56:4.95:5.09. Methylation analysis, FT-IR, and (1)H NMR spectroscopy analysis revealed that CNP-1-2 might have a backbone consisting of 1,4-linked Glcp, 1,3-linked Glcp, 1,3-linked Manp, 1,4-linked Galp, 1,2,6-linked Galp and 1,2,6-linked Galp. Its side chain might be composed of 1 linked Araf, 1,6-linked Galp and 1-linked Rhap residues. AFM (atomic force micrograph) analysis revealed that CNP-1-2 had the molecular aggregation along with branched and entangled structure. PMID- 26686181 TI - Synthesis of kenaf cellulose carbamate and its smart electric stimuli-response. AB - Cellulose carbamate (CC) was produced from kenaf core pulp (KCP) via a microwave reactor-assisted method. The formation of CC was confirmed by Fourier transform infrared spectroscopy and nitrogen content analysis. The degree of substitution, zeta potential and size distribution of CC were also determined. The CC was characterized with scanning electron microscopy, X-ray diffraction and thermogravimetry analysis. The CC particles were then dispersed in silicone oil to prepare CC-based anhydrous electric stimuli-responsive electrorheological (ER) fluids. Rhelogical measurement was carried out using rotational rheometer with a high voltage generator in both steady and oscillatory shear modes to examine the effect of electric field strength on the ER characteristics. The results showed that the increase in electric field strength has enhanced the ER properties of CC based ER fluid due to the chain formation induced by electric polarization among the particles. PMID- 26686183 TI - Preparation, analysis and antioxidant evaluation of the controlled product of polysaccharide from Mactra veneriformis by mild acid hydrolysis. AB - The polysaccharides from Mactra veneriformis (MVPS) were degraded by controlled mild acid hydrolysis to produce active oligosaccharides. MVPS can easily be hydrolyzed by H2SO4 or HCl. The hydrolyzing process was investigated in acid addition and reaction time by evaluating the producing content of reducing sugar. Hydrolysis with 1M HCl to MVPS can generate a time-depended behavior that is mild and controllable. HPLC analysis monitored the change of oligosaccharides composition in hydrolyzing. Total nine oligosaccharides are recognizable in the HPLC profile, and their content showed a regular transformation in hydrolysis. Those nine ingredients were identified as glucooligosaccharides with DP from 1 to 7 by MS analysis. Antioxidant activities of the typical hydrolyzates as well as MVPs were further tested in assays of DPPH and hydroxyl radicals scavenging, and reducing power. It was found that HCl hydrolyzate exhibited stronger antioxidant effects than MVPS and H2SO4 hydrolyzate due to its higher content of oligosaccharides. PMID- 26686184 TI - Metal doped carbon nanoneedles and effect of carbon organization with activity for hydrogen evolution reaction (HER). AB - Cellulose nanowhiskers (CNW) from cotton, was prepared by acid hydrolysis and purified using a size selection process to obtain homogeneous samples with average particle size of 270 nm and 85.5% crystallinity. Purified CNW was used as precursor to carbon nanoneedles (CNN) synthesis. The synthesis of CNN loaded with different metals dopants were carried out by a nanoreactor method and the obtained CNNs applied as electrocatalysts for hydrogen evolution reaction (HER). In the carbon nanoneedles synthesis, Ni, Cu, or Fe worked as graphitization catalyst and the metal were found present as dopants in the final material. The used metal appeared to have direct influence on the degree of organization of the particles and also in the surface density of polar groups. It was evaluated the influence of the graphitic organization on the general properties and nickel was found as the more appropriate metal since it leads to a more organized material and also to a high activity toward HER. PMID- 26686185 TI - Facile synthesis of cobalt ferrite nanotubes using bacterial nanocellulose as template. AB - A facile method for the preparation of cobalt ferrite nanotubes by use of bacterial cellulose nanoribbons as a template is described. The proposed method relays on a simple coprecipitation operation, which is a technique extensively used for the synthesis of nanoparticles (either isolated or as aggregates) but not for the synthesis of nanotubes. The precursors employed in the synthesis are chlorides, and the procedure is carried out at low temperature (90 degrees C). By the method proposed a homogeneous distribution of cobalt ferrite nanotubes with an average diameter of 217 nm in the bacterial nanocellulose (BC) aerogel (3%) was obtained. The obtained nanotubes are formed by 26-102 nm cobalt ferrite clusters of cobalt ferrite nanoparticles with diameters in the 9-13 nm interval. The nanoparticles that form the nanotubes showed to have a certain crystalline disorder, which could be attributed in a greater extent to the small crystallite size, and, in a lesser extent, to microstrains existing in the crystalline lattice. The BC-templated-CoFe2O4 nanotubes exhibited magnetic behavior at room temperature. The magnetic properties showed to be influenced by a fraction of nanoparticles in superparamagnetic state. PMID- 26686186 TI - Preparation and characterization of bio-based hybrid film containing chitosan and silver nanowires. AB - A bio-based hybrid film containing chitosan (CS) and silver nanowires (AgNWs) has been prepared by a simple casting technique. X-ray diffraction (XRD), Fourier infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and UV-visible spectroscopy were employed to characterize the structure of bio-based film. The bio-based hybrid film showed unique performance compared with bare chitosan film. The incorporated nano-silver could improve the strength properly. The results revealed that AgNWs in CS film, improved its tensile strength more than 62% and Young modulus 55% compared with pure chitosan film. On the other hand tensile strength was increased 36.7% with AgNPs. Importantly, the film also exhibited conductivity and antibacterial properties, which may expand its future application. PMID- 26686187 TI - Molecular properties and antioxidant activities of polysaccharides isolated from alkaline extract of wild Armillaria ostoyae mushrooms. AB - This study aims to discover novel and bioactive polysaccharides (PS) from wild Armillaria ostoyae, a honey mushroom species. Two PS designated AkPS1V-1 (66.6 kDa) and AkPS1V-2 (15.3 kDa) were isolated and fractionated by anion ion exchange (IEC) and size exclusion chromatography (SEC) from the alkaline extract of A. ostoyae mushrooms. AkPS1V-1 was a glucan composed of solely glucose residues and AkPS1V-2 a heteropolysaccharide composed of glucose and galactose at 6:1 molar ratio. AkPS1V-2 exhibited higher antioxidant activities than AkPS1V-1 based on reducing power, radical scavenging and metal chelating assays. The structure of AkPS1V-2 was further analyzed and elucidated as a branched galactoglucan with a backbone composed of (1->6)-beta-D-glucopyranosyl, (1->3)-beta-D-glucopyranosyl, (1->3)-alpha-D-galactopyranosyl and (1->3,6)-beta-D-glucopyranosyl residues at 3:1:1:1 ratio, and side chain of (1->3)-beta-D-glucopyranosyl residue. This is the first report on a pure PS structure and its antioxidant activities from this mushroom species. PMID- 26686188 TI - Postnatal exposure to PFOS, but not PBDE 99, disturb dopaminergic gene transcription in the mouse CNS. AB - The CNS of breast feeding infants and toddlers may be exposed to persistent organic pollutants via lactational transfer. Here, 10 days old mice were exposed to single oral doses of either PFOS, PBDE99 or vehicle control and were examined for changes in dopaminergic gene transcription in CNS tissue collected at 24h or 2 months post exposure.qPCR analyses of brain tissue from mice euthanized 24h post exposure revealed that PFOS affected transcription of Dopamine receptor-D5 (DRD5) in cerebral cortex and Tyrosine hydroxylase (TH) in the hippocampus. At 2 months of age, mice neonatally exposed to PFOS displayed decreased transcription of Dopamine receptor-D2 (DRD2) and TH in hippocampus. No significant changes in any of the tested genes were observed in PBDE99 exposed mice. This indicates that PFOS, but not PBDE99, affects the developing cerebral dopaminergic system at gene transcriptional level in cortex and hippocampus, which may account for some of the mechanistic effects behind the aetiology of neuropsychiatric disorders. PMID- 26686189 TI - Synergistic effect of radon and sodium arsenite on DNA damage in HBE cells. AB - Human epidemiological studies showed that radon and arsenic exposures are major risk factors for lung cancer in Yunnan tin miners. However, biological evidence for this phenomenon is absent. In this study, HBE cells were exposed to different concentrations of sodium arsenite, different radon exposure times, or a combination of these two factors. The results showed a synergistic effect of radon and sodium arsenite in cell cytotoxicity as determined by cell viability. Elevated intracellular ROS levels and increased DNA damage indexed by comet assay and gamma-H2AX were detected. Moreover, DNA HR repair in terms of Rad51 declined when the cells were exposed to both radon and sodium arsenite. The synergistic effect of radon and sodium arsenite in HBE cells may be attributed to the enhanced DSBs and inhibited HR pathway upon co-exposure. PMID- 26686190 TI - Binary and Tertiary Mixtures of Satureja hortensis and Origanum vulgare Essential Oils as Potent Antimicrobial Agents Against Helicobacter pylori. AB - Essential oils possess strong antimicrobial activity, even against multiresistant Helicobacter pylori. Available therapies against H. pylori infection have multiple disadvantages, indicating a great need for a development of new therapeutics. The purpose of this study was to develop a potent natural product based anti-H. pylori formulation. First, anti-H. pylori activity of nine essential oils was determined, after which the most active oils were mixed in various ratios for further testing. Satureja hortensis, Origanum vulgare subsp. vulgare and O. vulgare subsp. hirtum essential oils expressed the highest activity (MIC = 2 MUL mL(-1)). Their binary and ternary mixtures exhibited notably higher antimicrobial activity (MIC <= 2 MUL mL(-1)). The most active was the mixture of S. hortensis and O. vulgare subsp. hirtum oils in volume ratio 2:1, which expressed 4 times higher activity than individual oils (MIC = 0.5 MUL mL(-1)). According to GC-MS, both oils in the mixture were characterized by high content of phenols (48-73%), with carvacrol as the main carrier of antimicrobial activity. Presented in vitro study pointed out binary mixture of S. hortensis and O. vulgare subsp. hirtum essential oils in volume ratio 2:1 as promising candidate for further in vivo studies targeting H. pylori infection. PMID- 26686191 TI - AUTHOR RESPONSE. PMID- 26686193 TI - Partial Nephrectomy in the Overweight Patient: an Overview. AB - The diagnosis and treatment of kidney cancer continues to evolve with advances in imaging and surgical approaches. The use of nephron sparing surgery (NSS) has become the operation of choice for treating small renal masses. Yet, technical difficulty and a variety of approaches have left debate for best method in the overweight population. This review summarizes the current knowledge in the open, laparoscopic, and robotic approaches to identify key risk factors, general assessments, complication rates, and the influence of body habitus for each approach. PMID- 26686192 TI - Stem Cell Therapy for Interstitial Cystitis/Bladder Pain Syndrome. AB - Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disease characterized by pelvic pain, usually with urinary frequency. These symptoms make patients suffer from a poor quality of life. However, there is still a lack of consensus on the pathophysiology and curable treatment of IC/BPS. We have reviewed several candidates for the pathophysiology of this disease and also treatments that have been used. Although several oral medications, bladder instillation therapies, fulguration for Hunner's lesion, and hydrodistention have been tried as IC/BPS treatments, their outcomes have not been satisfactory. As the application of stem cell therapy is expanding into the urologic field, innovative strategies have been tested with animal models of IC/BPS and have shown promising therapeutic effects for reversing the symptoms of this disorder. Although several concerns about stem cell sources and their safety should be addressed before initiating human clinical trials, we introduce stem cell therapy as a valuable future treatment approach for IC/BPS. PMID- 26686194 TI - Testing Dragonflies as Species Richness Indicators in a Fragmented Subtropical Atlantic Forest Environment. AB - We surveyed 15 bodies of water among remnants of the Atlantic Forest biome in southern Brazil for adult dragonflies and damselflies to test whether an empirical selection method for diversity indicators could be applied in a subtropical ecosystem, where limited ecological knowledge on species level is available. We found a regional species pool of 34 species distributed in a nested subset pattern with a mean of 11.2 species per locality. There was a pronounced difference in species composition between spring, summer, and autumn, but no differences in species numbers between seasons. Two species, Homeoura chelifera (Selys) and Ischnura capreolus (Hagen), were the strongest candidates for regional diversity indicators, being found only at species-rich localities in our surveyed area and likewise in an undisturbed national forest reserve, serving as a reference site for the Atlantic Forest. Using our selection method, we found it possible to obtain a tentative list of diversity indicators without having detailed ecological information of each species, providing a reference site is available for comparison. The method thus allows for indicator species to be selected in blanco from taxonomic groups that are little known. We hence argue that Odonata can already be incorporated in ongoing assessment programs in the Neotropics, which would also increase the ecological knowledge of the group and allow extrapolation to other taxa. PMID- 26686195 TI - Pregnancy and Birth Outcomes Among Primiparae at Very Advanced Maternal Age: At What Price? AB - OBJECTIVES: In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged >=45) compared to younger primiparae. METHODS: Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30-35, delivering at Sheba Medical Center from 2008 through 2013. RESULTS: VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45-49 and >=50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. CONCLUSIONS: Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged. PMID- 26686196 TI - DICER1-Negative Pleuropulmonary Blastoma in a Patient With Selective IgA Deficiency. PMID- 26686197 TI - Development and validation of SPMMTE HPLC method for analysis of profens from human plasma. AB - A fast, selective and reproducible solid-phase membrane microtip extraction (SPMMTE) HPLC method has been developed and validated for the analyses of ibuprofen, ketoprofen, and flurbiprofen from human plasma. The analysis was carried out on a C18 (150 * 4.6 mm; 5 MUm) column. The mobile phase used was water-acetonitrile (55:45, v/v) adjusted to pH 3.0 using trifluoroacetic acid, at a flow rate 0.5 mL/min with a detection wavelength of 225 nm. The values for the capacity factors for the profen samples ranged from 0.47 to 1.50. The values for the selectivity factor (alpha) for ketoprofen-flurbiprofen, flurbiprofen ibuprofen and ibuprofen-ketoprofen combinations from human plasma samples were 1.99, 1.00 and 2.10, respectively. The resolution factors (Rs) for ketoprofen flurbiprofen, flurbiprofen-ibuprofen and ibuprofen-ketoprofen from plasma samples were 3.00, 1.50 and 4.10, respectively. The percentage recoveries of ibuprofen, ketoprofen, and flurbiprofen from human plasma were 75-85%. All of the profens were separated within 7.0 min, indicating a relatively fast method. During the development of the SPMMTE procedure the parameters of pH, contact time, desorption and types of solvents were optimized. The final method was also found to be efficient, effective and inexpensive. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26686199 TI - The benefits of cancer screening in kidney transplant recipients: a single-center experience. AB - The frequency of malignancy is increasing in kidney transplant recipients. Posttransplant malignancy (PTM) is a major cause of long-term graft survival inhibition. In this study, we evaluated the frequency and prognosis of PTM at our center and examined the efficacy of cancer screening. Between 1972 and 2013, 750 patients were followed-up at our center. Annual physical examinations and screenings were performed to detect PTM. We investigated the detail of two distinctive cancer groups: screening-detected cancers and symptom-detected cancers. Seventy-seven PTM were identified during the follow-up period. The mean age at the initial PTM detection was 43.6 +/- 12.8 years. The mean interval from transplantation to cancer diagnosis was 134.5 +/- 11.3 months. Among the 77 patients, posttransplant lymphoproliferative disease (PTLD) was the most common cancer (19.5%, 15/77), followed by renal cell carcinoma (15.6%, 12/77). Of the cancer cases, 46.8% (36/77) were detected via screening. The most frequently screening-detected cancer was renal cell carcinoma of the native kidney and breast cancer (22.2%, 8/36). However, it was difficult to detect PTLD, urothelial carcinoma, and colorectal cancer via screening. Interestingly, Cox proportional regression analyses revealed nonscreened recipients to be a significant prognostic factor for PTM (P < 0.001). This study is the first to report that appropriate screening tests play a key role in early PTM diagnosis and lead to reduce the mortality rate in kidney transplant recipients. These findings support the provision of long-term appropriate screening for kidney transplant recipients. PMID- 26686198 TI - Exploring the Major Sources and Extent of Heterogeneity in a Genome-Wide Association Meta-Analysis. AB - Genome-wide association (GWA) meta-analysis has become a popular approach for discovering genetic variants responsible for complex diseases. The between-study heterogeneity effect is a severe issue that may complicate the interpretation of results. Aiming to improve the interpretation of meta-analysis results, we empirically explored the extent and source of heterogeneity effect. We analyzed a previously reported GWA meta-analysis of obesity, in which over 21,000 subjects from seven individual samples were meta-analyzed. We first evaluated the extent and distribution of heterogeneity across the entire genome. We then studied the effects of several potentially confounding factors, including age, ethnicity, gender composition, study type, and genotype imputation on heterogeneity with a random-effects meta-regression model. Of the total 4,325,550 SNPs being tested, heterogeneity was moderate to very large for 25.4% of the total SNPs. Heterogeneity was more severe in SNPs with stronger association signals. Ethnicity, average age, and genotype imputation accuracy had significant effects on the heterogeneity. Exploring the effects of ethnicity can provide clues to the potential ethnic-specific effects for two loci known to affect obesity, MC4R, and MTCH2. Our analysis can help to clarify understanding of the obesity mechanism and may provide guidance for an effective design of future GWA meta-analysis. PMID- 26686200 TI - Leaf morphophysiology of a Neotropical mistletoe is shaped by seasonal patterns of host leaf phenology. AB - Several mistletoe species are able to grow and reproduce on both deciduous and evergreen hosts, suggesting a degree of plasticity in their ability to cope with differences in intrinsic host functions. The aim of this study was to investigate the influence of host phenology on mistletoe water relations and leaf gas exchange. Mistletoe Passovia ovata parasitizing evergreen (Miconia albicans) hosts and P. ovata parasitizing deciduous (Byrsonima verbascifolia) hosts were sampled in a Neotropical savanna. Photosynthetic parameters, diurnal cycles of stomatal conductance, pre-dawn and midday leaf water potential, and stomatal anatomical traits were measured during the peak of the dry and wet seasons, respectively. P. ovata showed distinct water-use strategies that were dependent on host phenology. For P. ovata parasitizing the deciduous host, water use efficiency (WUE; ratio of photosynthetic rate to transpirational water loss) was 2-fold lower in the dry season than in the wet season; in contrast, WUE was maintained at the same level during the wet and dry seasons in P. ovata parasitizing the evergreen host. Generally, mistletoe and host diurnal cycles of stomatal conductance were linked, although there were clear differences in leaf water potential, with mistletoe showing anisohydric behaviour and the host showing isohydric behaviour. Compared to mistletoes attached to evergreen hosts, those parasitizing deciduous hosts had a 1.4-fold lower stomatal density and 1.2 fold wider stomata on both leaf surfaces, suggesting that the latter suffered less intense drought stress. This is the first study to show morphophysiological differences in the same mistletoe species parasitizing hosts of different phenological groups. Our results provide evidence that phenotypical plasticity (anatomical and physiological) might be essential to favour the use of a greater range of hosts. PMID- 26686201 TI - A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI?9041). AB - BACKGROUND: There is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity. METHODS: Patients were enrolled using 3 + 3 design, and were given intravenous trebananib and temsirolimus on Day 1, 8, 15 and 22 of a 28-day cycle. Dose limiting toxicities (DLTs) were evaluated during cycle 1. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP). Sparse pharmacokinetic (PK) sampling for trebananib drug levels was performed on Day 1 and 8 of cycle 2. RESULTS: Twenty-one patients were enrolled, 6 at dose level (DL) 1, 7 at DL -1, and 8 at DL -2. No effect of temsirolimus on trebananib PK was observed. The most common treatment-related adverse events (AEs) were: fatigue (81 %), edema (62 %), anorexia (57 %), nausea (52 %), rash (43 %) and mucositis (43 %). The most common grade >= 3 AEs included lymphopenia (28 %) and fatigue (28 %). The MTD was exceeded at DL-2. Of 18 response evaluable patients, 1 partial response was observed (ER+/HER2-/PIK3CA mutant breast cancer) and 4 patients had prolonged SD >= 24 weeks. No correlation with clinical benefit was observed with change in number TEMs or TP expression in TEMs with treatment. CONCLUSIONS: The MTD was exceeded at trebananib 10 mg/kg weekly and temsirolimus 20 mg weekly, with frequent overlapping toxicities including fatigue, edema, and anorexia. PMID- 26686203 TI - Crystal storing histiocytosis clinically mimicking metastatic carcinoma: Report of a case and reviews of literature. AB - BACKGROUND: Crystal storing histiocytosis (CSH) is a rare disorder characterized by accumulation of histiocytes containing crystalline material inclusions. This entity can be misdiagnosed as infection or tumor. We present a case of idiopathic CSH mimicking metastatic squamous cell carcinoma in a cervical lymph node and review of literature regarding this rare entity. METHODS AND RESULTS: The patient was a 70-year-old man with a medical history of squamous cell carcinoma of the right base of the tongue. The patient presented with an enlarged cervical lymph node, which was clinically diagnosed as metastatic carcinoma. At intraoperative consultation, it was unexpectedly discovered that the lymph node exhibited extensive histiocytosis containing crystal materials. Final pathology identified "crystal storing histiocytosis" because of amyloidal depositions. No metastatic carcinoma was seen. CONCLUSION: After 10 months of follow-up, the patient is disease free. To the best of our knowledge, this unusual clinical presentation is the first to describe CSH mimicking a metastatic carcinoma. PMID- 26686202 TI - Low serum uric acid levels in progressive supranuclear palsy. AB - INTRODUCTION: Uric acid is a natural antioxidant, and it has been shown that low levels of uric acid could be a risk factor for the development of PD. Our aim was to investigate whether uric acid plays a role in PSP. METHODS: We carried out a cross-sectional study to compare serum uric acid levels between PSP patients, PD patients, and healthy controls. We also analyzed longitudinal uric acid levels in the PSP group. RESULTS: PSP patients showed reduced levels of serum uric acid as compared to healthy controls. This reduction was similar to that found in patients with PD. Uric acid levels of PSP patients did not change with time. CONCLUSION: Serum uric acid levels are reduced in PSP as well as in PD compared to healthy controls. Our data suggest that high levels of uric acid could be a natural protective factor against PSP. PMID- 26686204 TI - Universal sinus computed tomography protocol for diagnostic imaging and intraoperative navigation. AB - BACKGROUND: Sinus computed tomography (CT) is performed for the diagnosis of paranasal sinus disease and to assess response to medical therapy. In addition, sinus CT is used for intraoperative imaging guidance. Multiple CTs increase cost and radiation exposure. OBJECTIVE: To determine potential cost savings and radiation dose reduction that result from the use of a single universal sinus CT protocol for diagnostic imaging and intraoperative navigation. MATERIALS AND METHODS: For sinus CT at the authors' institution, a single imaging protocol was begun and deemed acceptable by neuroradiologists and surgeons for diagnostic imaging and intraoperative guidance. The electronic medical record was queried over a 4-year period to determine the number of sinus CTs performed, dose-length products, referring providers' specialties, percentage of CTs used for intraoperative navigation, and the elapsed time between CT and surgery. RESULTS: A total of 6187 sinus CTs were performed by using a 64-detector scanner during the study period (2759 women and 3428 men; 53.6 +/- 16.7 years [mean +/- SD]), and 596 endoscopic sinus surgery cases used imaging guidance, for which all the CTs were deemed technically adequate. The mean dose-length product for the CTs was 338.4 +/- 31.9 mGy-cm (mean +/- SD). Of the 3702 sinus CTs ordered by nonotolaryngology providers, 167 surgeries with intraoperative navigation (4.5%) were performed. A higher percentage of CT referrals from sinus surgeons (23.9%) and other otolaryngology providers (11.4%) was used for imaging guidance (p < 0.0001). The time interval between sinus CT and surgery was greatest for nonotolaryngology providers (63.1 days, p < 0.01). Based on Medicare reimbursement, the total estimated saving was $147,628. CONCLUSIONS: Adopting a single universal sinus CT protocol for diagnostic imaging and intraoperative navigation can be an effective means of decreasing cost and radiation exposure. However, successful implementation must take into account multiple practice-based considerations. PMID- 26686205 TI - A rare and emerging entity: Sinonasal IgG4-related sclerosing disease. AB - BACKGROUND: Immunoglobulin G4 (IgG4) related sclerosing disease (rSD) is a new disease entity, first described in 2001, that involves autoimmune pancreatitis. Considered a systemic disease with lesions described in multiple organ systems, IgG4-rSD that affects the sinonasal region is rare. Our goal was to highlight the sinonasal presentation of this unique disease and to review previously reported adult cases from 2003 to 2014. METHODS: Case report (a 72-year-old man who presented with left exophthalmos, periorbital pain, and epiphora) and review of the literature. RESULTS: Radiographic workup with computed tomography and magnetic resonance imaging demonstrated a left sinonasal mass that involved the left maxillary and ethmoid sinuses, with surrounding bony destruction and orbital invasion. Nasal endoscopy demonstrated a fibrous lesion emanating in the middle meatus, with surrounding mucosal inflammation. The patient underwent an endoscopic biopsy, medial maxillectomy, and ethmoidectomy with tumor debulking. Pathology demonstrated inflamed respiratory mucosa with dense lymphoplasmacytic infiltrate and fibrosis; flow cytometry demonstrated no malignant cell populations; immunophenotyping demonstrated multiple foci of IgG4 cells. Plasma IgG4 was elevated in the setting of normal total IgG. The patient was treated with postoperative systemic and topical corticosteroids. Surveillance imaging studies and nasal endoscopy demonstrated disease resolution without recurrence. CONCLUSIONS: Sinonasal IgG4-rSD is a rare disease that can present with bony and soft-tissue invasion. This was an exceptional case, with osseous involvement and orbital invasion. Immunohistologic workup is essential for diagnosis. It is important to differentiate this disease from sinonasal tumors. Treatment includes corticosteroids and surgical debulking. Sinonasal IgG4-rSD represents an emerging disease that may present challenges for future rhinologists. PMID- 26686206 TI - Surgical relationship of the nasolacrimal system to the maxillary line: Performing safe mega antrostomy. AB - BACKGROUND: Endoscopic extended maxillary mega-antrostomy (EMMA) is a mucosal sparing technique that allows maxillary drainage by gravity, with a reported symptomatic nasolacrimal duct injury incidence of 0-4%, based on history alone. Injury to the nasolacrimal duct is known to cause epiphora, a complication that is rare but more often seen in this revision surgery. OBJECTIVE: The goal of this study was to determine the incidence of nasolacrimal system penetration during EMMA. We, in addition, sought to determine the minimal safe distance from the midpoint of the maxillary line (the "M" point) to the nasolacrimal system to avoid this injury. METHODS: Six cadaveric heads underwent bilateral Jones II test followed by EMMA. Measurements from the M point to the antrostomy were recorded. The Jones II test was then repeated to assess for penetration and/or injury of the nasolacrimal system. If no penetration occurred at the surgical limit of EMMA, then dissection was continued incrementally until penetration occurred. This measurement was recorded. RESULTS: Lacrimal duct violation was identified in 5 of 12 procedures (42%). Lacrimal duct penetration occurred at an average of 3.7 mm (range, 2-7 mm) posterior to the M point. CONCLUSION: Subclinical lacrimal system injury is likely to occur during EMMA. These findings would indicate that maintaining a distance of >7 mm from the maxillary line could avoid this injury. PMID- 26686207 TI - Association between chronic acetaminophen exposure and allergic rhinitis in a rat model. AB - BACKGROUND: Several population studies demonstrated an increased risk of allergic rhinitis in patients exposed to acetaminophen. However, no histologic studies have been conducted to assess the relationship between acetaminophen exposure and allergic rhinitis. OBJECTIVE: In this study, we investigated the association between chronic acetaminophen exposure and the development of allergic rhinitis in a rat model. METHODS: Ten female Sprague-Dawley rats were randomly assigned to either a control (n = 5) or an acetaminophen group (n = 5). The acetaminophen group received 200 mg/kg/day of acetaminophen suspended in yogurt via oral gavage for 120 days. The control group received only the yogurt vehicle. Allergic behavioral responses, including nose rub, eye rub, ear scratching, and neck and/or face scratching, were quantified. The rats were killed, and the noses were harvested. The portion of the nose, including the nasal septum and the inferior turbinates, was embedded in paraffin, sectioned, and stained with hematoxylin and eosin to quantify the inflammatory infiltrate. RESULTS: The average number of allergic responses per animal was 13.2 in the acetaminophen group versus 6.2 in the control group (p = 0.032). All the rats in the acetaminophen group (100%) had mast cells infiltrating the lamina propria of the inferior turbinate, whereas mast cells were detected in only 40% of the animals in the control group. The average number of mast cells per animal in the acetaminophen group was 134 versus 21 in the control group (p = 0.048). CONCLUSIONS: Our study was the first to demonstrate a histologic association between chronic exposure to acetaminophen and rhinitis. Further research to elucidate the mechanism that underlies these findings is necessary. PMID- 26686208 TI - Association of interleukin 7 receptor (rs1494555 and rs6897932) gene polymorphisms with asthma in a north Indian population. AB - BACKGROUND: Interleukin 7R (IL-7R), a cytokine receptor gene, plays an important role in the development of innate and adaptive inflammatory response in asthma etiology. OBJECTIVE: IL-7R is a heterodimeric protein composed of alpha chain and gamma chain. The alpha chain of IL-7R has a range of single nucleotide polymorphisms, which give rise to nonsynonymous amino-acid substitutions that might result in an increased production of inflammatory cytokines and cause asthma. METHODS: A case-control study was conducted with a total of 964 subjects, including 483 healthy controls and 481 patients with asthma. DNA samples were extracted from blood, and genotyping was done by using sequence-specific-primer polymerase chain reaction. RESULTS: Statistical analysis revealed that IL-7R + 1237A/G (rs1494555) gene polymorphism shows a highly protective association toward asthma (odds ratio [OR] 0.56, p < 0.001) in AG genotype as well as in mutant GG genotype (OR 0.64, p = 0.029). However, IL-7R + 2087T/C (rs6897932) polymorphism showed an increased risk toward asthma in TC genotype (OR 1.70, p = 0.002) as well as in the CC genotype (OR 1.68, p = 0.002). Furthermore, the GT and AC haplotypes in the IL-7R polymorphisms were also found to be significantly associated with asthma (p < 0.001 and p = 0.037, respectively). CONCLUSIONS: The study conducted in a north Indian population indicated that the protective association was observed for the +1237A/G position, and a significant risk was observed for the +2087T/C position in asthma. PMID- 26686209 TI - Ragweed allergy: Pollen count and sensitization and allergy prevalence in two Italian allergy centers. AB - BACKGROUND: Ragweed allergy represents a challenge for allergists due to its increase in some geographic areas, mainly northern Italy. OBJECTIVES: To compare two allergy centers in northern Italy by analyzing both the pollen count and the patient characteristics (sensitization and allergy prevalence) over a 10-year period. METHODS: Pollen counts for 10 years (2004-2013) were evaluated and compared in the two centers. Characteristics of patients who were sensitized and allergic to ragweed were analyzed. RESULTS: There was a significantly higher pollen count in Busto Arsizio than in Novi Ligure (p < 0.001). The patients who were seen in the Busto Arsizio center showed more frequent sensitization (p < 0.01) and allergy (p < 0.05) to ragweed than patients who were seen in the Novi Ligure center. The pollen count was significantly (p < 0.01) associated with sensitization and allergy difference. Allergic asthma was more frequent (p < 0.05) in Busto Arsizio. CONCLUSIONS: The pattern of sensitization and allergy prevalence seemed to be associated with ragweed pollen pressure, such as quantity. The knowledge of the pollen count is relevant in clinical practice, mainly for the management of patients with allergy. PMID- 26686210 TI - Fungal septal abscess complicating maxillary sinus fungus balls in an immunocompetent host. AB - BACKGROUND: Fungal infections of the nasal cavity can be destructive entities that are typically seen in immunocompromised hosts. We present a case of a localized fungal abscess of the nasal septum in an immunocompetent host after endoscopic treatment of maxillary sinus fungus balls. METHOD: A 51-year-old woman with a history of asthma and recent treatment with oral steroids presented with bilateral maxillary sinus mycetomas. She underwent endoscopic sinus surgery. The postoperative course was complicated by an asthma flare, which required oral steroids. The patient returned with nasal obstruction, and results of a physical examination were consistent with a nasal septal abscess. Drainage was attempted, and cultures showed fungal elements. The abscess reaccumulated, and the patient was referred to our institution. Operative drainage was performed with placement of a catheter in the septal abscess cavity. Forty-eight hours of amphotericin irrigations were performed through this site. The patient was started on oral antifungal therapy. Results of an immune workup, including testing for human immunodeficiency virus and assessing immunoglobulin levels, were negative. Final fungal cultures grew Scedosporium apiospermum sensitive to voriconazole. The patient completed therapy without further recurrence. Follow-up at 6 months demonstrated no further recurrence of her fungal septal infection. CONCLUSION: Sinonasal fungal infections rarely occur in immunocompetent hosts. The septum may have been seeded during the endoscopic sinus surgery. The use of oral steroids may have been a risk factor for the development of an aggressive nasal septal fungal abscess in this patient. This is the first reported case of a nasal septal abscess in an otherwise immunocompetent host with S. apiospermum. PMID- 26686211 TI - Delayed presentation of traumatic cerebrospinal fluid rhinorrhea: Case report and literature review. AB - Cerebrospinal fluid (CSF) leak is one of several complications that can occur after traumatic skull base injury. Although most patients present soon after the injury occurs, some can present years later, with resulting morbidity and the need for additional procedures. We present a case of a patient with a sphenoid sinus CSF leak who presented 12 years after a closed head injury that included a sphenoethmoid skull base fracture. We also reviewed the literature on this topic, with a discussion of previous reports of CSF leaks that occurred months, years, or decades after trauma. A late onset CSF leak appears to be a rare but important complication of traumatic skull base injury. This case highlights the need for clinicians to remain vigilant to the possibility of delayed CSF rhinorrhea, even years after traumatic head injury. PMID- 26686212 TI - Nasolacrimal duct obstruction caused by lymphoproliferative infiltration in the course of chronic lymphocytic leukemia. AB - BACKGROUND: Endoscopic dacryocystorhinostomy (DCR) is the standard treatment of nasolacrimal duct obstruction. Only in rare cases, blockage may be caused by malignant tumors and even more exceptionally by lymphatic neoplasms so that biopsies are not routinely taken for diagnostic purposes. METHODS: A computerized retrieval system was used for this retrospective study to identify all patients with histologically documented lymphoproliferative infiltration in the lacrimal drainage system from 2001 to 2009. RESULTS: In four of 191 patients (2.1%), infiltration of the nasolacrimal sac mucosa with a small lymphocytic lymphoma (SLL)/chronic lymphatic leukemia (CLL) was found. Patients who develop symptoms like epiphora within the course of known CLL are highly suspicious for lymphoproliferative infiltration of the lacrimal drainage associated lymphoid tissue. CONCLUSION: A proactive approach with ophthalmologic consultation and DCR should be followed in these patients to avoid dacryocystitis. PMID- 26686213 TI - Endoscopic endonasal resection of a giant middle fossa epidermoid cyst. AB - Intracranial epidermoid cysts are rare. We report a case of a 55-year-old man who presented with trigeminal neuralgia and was found, on imaging, to have an epidermoid cyst located in the right middle fossa. He was managed via an entirely endoscopic endonasal approach. Postoperative magnetic resonance imaging confirmed complete removal of the mass, and the patient continued to have complete resolution of symptoms at a 1-year follow-up. PMID- 26686214 TI - Ovomucoid specific immunoglobulin E as a predictor of tolerance to cooked egg. AB - BACKGROUND: Ovomucoid is the dominant allergen in hen's egg. Although several studies evaluated the utility of ovomucoid specific immunoglobulin E (sIgE) levels in predicting baked (e.g., muffin or cupcake) or raw egg food challenge outcomes, studies that evaluated ovomucoid sIgE as a predictor of cooked egg (e.g., scrambled or hard boiled) challenge outcomes are limited. OBJECTIVE: To determine the relation of ovomucoid sIgE levels with cooked egg food challenge outcomes. METHODS: A retrospective review of 44 children who underwent cooked egg food challenge and who had the ovomucoid sIgE level measured. RESULTS: Thirty-six of 44 children (81.8%) passed cooked egg challenge. The ovomucoid sIgE level predicted cooked egg challenge outcome (passed median, <0.35 kU/L [range, <0.35 0.64 kU/L]; failed median, 0.40 kU/L [range, <0.35-3.13 kU/L]; p = 0.004). Ovomucoid sIgE levels correlated with egg white (EW) sIgE levels (Spearman correlation coefficient, 0.588; p < 0.001). Receiver operating characteristic curve analysis of ovomucoid and EW sIgE demonstrated areas under the curve of 0.711 and 0.766, respectively. No significant difference was observed among those immunologic parameters in their abilities to predict cooked egg challenge outcome (p = 0.559). CONCLUSION: The ovomucoid sIgE level may be helpful in predicting cooked egg challenge outcomes. However, our study did not support a role for ovomucoid sIgE replacing EW sIgE testing in evaluating egg allergy. PMID- 26686222 TI - Optically transparent high temperature shape memory polymers. AB - Optically transparent shape memory polymers (SMPs) have potential in advanced optoelectronic and other common shape memory applications, and here optically transparent shape memory polyimide is reported for the first time. The polyimide possesses a glass transition temperature (Tg) of 171 degrees C, higher than the Tg of other transparent SMPs reported, and the influence of molecular structure on Tg is discussed. The 120 MUm thick polyimide film exhibits transmittance higher than 81% in 450-800 nm, and the possible mechanism of its high transparency is analyzed, which will benefit further research on other transparent high temperature SMPs. The transparent polyimide showed excellent thermomechanical properties and shape memory performances, and retained high optical transparency after many shape memory cycles. PMID- 26686215 TI - Review: Immunology of sinusitis, trauma, asthma, and sepsis. AB - BACKGROUND: This review article is important for allergists/immunologists and otolaryngologists. It discussed chronic rhinosinusitis, epidemiology, pathogenesis, innate adaptive immunology, nuclear factor-kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma, sinusitis, elderly pathogenesis, oxidative stress, depression, seasonal variation, vitamin D, genetic susceptibility and sepsis, hereditary angioedema related to trauma and stress. OBJECTIVE: The objective of this review is to link chronic rhinosinusitis, epidemiology, innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma and sinusitis. METHODS: A literature search was conducted from several articles, prospective studies, recent reviews and earlier reports. A synergistic relationship develops between activation of the innate immune system and the loss of organ barrier functions. Many complex factors, such as genetics, physical agents, mediators in the development of organ failure both in asthma, sinusitis, stress, depression and trauma, leading to posttraumatic organ failure. Asthma and sepsis, a common condition encountered in hospital environments remains an important cause of death at intensive care units where allergists/immunologists and otolaryngologists are frequently consulted. The patient's immune surveillance could fail to eliminate the pathogen, allowing it to spread and there is a proinflammatory mediator release with inappropriate activation. CONCLUSION: This review discussed chronic rhinosinusitis, sinusitis related to trauma, the innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, inflammation, reactive oxygen species, asthma pathogenesis, and asthma in the elderly, oxidative stress, depression, seasonal variation and vitamin D, cytokines, genetic susceptibility related to sepsis, hereditary angioedema related to trauma and stress. PMID- 26686223 TI - The severity of sediment desiccation affects the adsorption characteristics and speciation of phosphorus. AB - Phosphorus is an important nutrient for plants and algae, and can be the limiting nutrient in aquatic ecosystems. However, oversupply can lead to significant water quality issues. The largest source and sink of P in most aquatic systems is the sediment. As a consequence of drought, in many places sediments that normally would have remained inundated are now being desiccated. Based on previous studies, it is often difficult to predict what impact drying will have on the cycling of P. This is because most of these studies have looked at drying across a chronosequence in the field, where there may be differences in sediment composition or microbial community structure. In this paper we present the results of a study where sediment was exposed to progressively more severe drying in the laboratory - starting with wet sediment, followed by air drying and then sequential oven drying at 30, 50 and 85 degrees C. Drying resulted in a shift in P speciation, notably with an increase in NaHCO3-extractable reactive P and a decline in NaHCO3-extractable unreactive P, likely indicating an increase in bioavailable, easily exchangeable P. Drying also resulted in a decline in the microbial-P fraction. Drying significantly affected the P adsorption characteristics of the sediment. The total amount of P adsorbed by the sediment and the linear adsorption co-efficient both declined, while the amount of native P adsorbed to the sediment and the equilibrium P concentration both increased. Drying also affected iron speciation with a shift from more reactive oxalate extractable Fe to more recalcitrant citrate-dithionate-bicarbonate-extractable Fe, suggesting an increase in iron crystallinity and hence decrease in P adsorption capacity. The increase in crystallinity is consistent with Fe EXAFS results, which showed that drying resulted in an increase in edge-sharing neighbours. We hypothesise that the shifts in P speciation, the decline in P adsorption capacity, the increase in the equilibrium P concentration, as well as the death of micro-organisms (as evidenced by a decline in microbial P) on drying all contribute to the Birch effect - the initial pulse of P and/or N upon inundation of dried soils or sediments. PMID- 26686224 TI - Evolutionary context for the association of gamma-globin, serum uric acid, and hypertension in African Americans. AB - BACKGROUND: Hyperuricemia and associated cardio-metabolic disorders are more prevalent in African Americans than in European Americans. We used genome-wide admixture mapping and association testing to identify loci with ancestry effects on serum uric acid levels. METHODS: We analyzed 1,976 African Americans from Washington, D.C, including 1,322 individuals from 328 pedigrees and 654 unrelated individuals, enrolled in the Howard University Family Study. We performed admixture mapping and genome-wide association testing using ~800 k autosomal single-nucleotide polymorphisms (SNPs). We performed fine mapping by dense genotyping. We assessed functionality by a combination of bioinformatic annotation, reporter gene assays, and gel shift experiments. We also analyzed 12,641 individuals enrolled in the National Health and Nutrition Examination Survey. RESULTS: We detected a genome-wide significant locus on chromosome 11p15.4 at which serum uric acid levels increased with increasing African ancestry, independent of kidney function. Fine-mapping identified two independent signals in the beta-globin locus. The ancestral allele at SNP rs2855126, located upstream of the hemoglobin, gamma A gene HBG1, was associated with increased serum uric acid levels and higher expression of a reporter gene relative to the derived allele. Hyperuricemia was associated with increased risk of hypertension in 3,767 African Americans (Odds Ratio = 2.48, p = 2.71 * 10(-19)). CONCLUSIONS: Given that increased expression of gamma-globin leads to increased levels of fetal hemoglobin which confers protection against malaria, we hypothesize that evolution in Africa of protection against malaria may have occurred at the cost of increased serum uric acid levels, contributing to the high rates of hyperuricemia and associated cardio-metabolic disorders observed in African Americans. PMID- 26686226 TI - Improved Doxorubicin Encapsulation and Pharmacokinetics of Ferritin-Fusion Protein Nanocarriers Bearing Proline, Serine, and Alanine Elements. AB - A novel human ferritin-based nanocarrier, composed of 24 modified monomers able to auto-assemble into a modified protein cage, was produced and used as selective carrier of anti-tumor payloads. Each modified monomer derives from the genetic fusion of two distinct modules, namely the heavy chain of human ferritin (HFt) and a stabilizing/protective PAS polypeptide sequence rich in proline (P), serine (S), and alanine (A) residues. Two genetically fused protein constructs containing PAS polymers with 40- and 75-residue lengths, respectively, were compared. They were produced and purified as recombinant proteins in Escherichia coli at high yields. Both preparations were highly soluble and stable in vitro as well as in mouse plasma. Size-exclusion chromatography, dynamic light scattering, and transmission electron microscopy results indicated that PASylated ferritins are fully assembled and highly monodispersed. In addition, yields and stability of encapsulated doxorubicin were significantly better for both HFt-PAS proteins than for wild-type HFt. Importantly, PAS sequences considerably prolonged the half-life of HFt in the mouse bloodstream. Finally, our doxorubicin-loaded nanocages preserved the pharmacological activity of the drug. Taken together, these results indicate that both of the developed HFt-PAS fusion proteins are promising nanocarriers for future applications in cancer therapy. PMID- 26686225 TI - IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer. AB - Interleukin-1 (IL-1) is a major "alarm" upstream pro-inflammatory cytokine that mainly acts by inducing cascades of cytokine and inflammation-promoting mediators. In the tumor arena, IL-1 is produced by both malignant and microenvironmental cells. IL-1alpha and IL-1beta are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. IL-1alpha and IL 1beta differ in their compartmentalization and in the producing cells. IL-1beta is only active in its inflammasome dependent processed and secreted form and has been considered as the major mediator of inflammation. On the other hand, IL 1alpha is mainly cell-associated in tissue resident cells, being also active in its precursor form. The role of the IL-1 molecules in the unique microenvironment in the colon is largely unknown. Here, we described the role of IL-1alpha and IL 1beta in colon homeostasis, colon inflammation, colon carcinogenesis and invasiveness of colorectal cancer. Understanding of the integrative role of IL 1alpha and IL-1beta in these processes will facilitate the application of novel IL-1 modulating approaches. PMID- 26686227 TI - Hospital Readmissions in Patients With Carbapenem-Resistant Klebsiella pneumoniae. AB - BACKGROUND: Various transmission routes contribute to spread of carbapenem resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated ("CRKP readmission") potentially contribute to transmission of CRKP. OBJECTIVE: To evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKLe). DESIGN: Cohort study from December 24, 2011, through July 1, 2013. SETTING: Multicenter consortium of acute care hospitals in the Great Lakes region. PATIENTS: All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP positive culture. METHODS: All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models. RESULTS: Fifty-six (20%) of 287 patients who were discharged alive had a CRKP readmission. History of malignancy was associated with CRKP readmission (adjusted odds ratio [adjusted OR], 3.00 [95% CI, 1.32-6.65], P<.01). During the index hospitalization, 160 patients (56%) received antibiotic treatment against CRKP; the choice of regimen was associated with CRKP readmission (P=.02). Receipt of tigecycline-based therapy (adjusted OR, 5.13 [95% CI, 1.72-17.44], using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission. CONCLUSION: Hospitalized patients with CRKP-specifically those with a history of malignancy-are at high risk of readmission with recurrent CRKP infection or colonization. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk. PMID- 26686229 TI - Adherence to a Mediterranean-Style Diet and Appendicular Lean Mass in Community Dwelling Older People: Results From the Berlin Aging Study II. AB - BACKGROUND: Selected nutrients or food groups have often been studied with regard to long-term mortality and cardiovascular disease, whereas the relation between diet quality and appendicular lean mass (ALM) has rarely been researched. OBJECTIVE: The aim of this study was to explore the association between a Mediterranean-style diet and ALM in community-dwelling older people. METHODS: Cross-sectional data from the Berlin Aging Study II were available for 1,509 participants (51% women, 68.2+/-3.7 years). Nutrient intake was assessed using the European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire. Adherence to a Mediterranean-style diet was evaluated with the modified Mediterranean-type diet score (mMedTypeDiet). ALM was determined by dual energy X-ray absorptiometry and related to body mass index (ALM/BMI). A general linear regression model was carried out to assess the association between mMedTypeDiet score groups and ALM/BMI. RESULTS: ALM/BMI was higher in women with a higher adherence to the mMedTypeDiet (0.64+/-0.1 vs 0.62+/-0.1 and 0.61+/-0.1 in low and medium adherence, retrospectively, p = .004). In the risk factor adjusted general linear regression analysis, a higher adherence to the mMedTypeDiet was associated with higher ALM/BMI in women and better ALM/fat mass ratio when compared to a medium and a low diet quality. No significant associations were seen in men. CONCLUSIONS: Higher adherence to a Mediterranean style diet was associated with a positive effect on ALM/BMI in women. PMID- 26686228 TI - LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia. AB - Some long non-coding RNAs (lncRNAs) participate in physiological processes that maintain cellular and tissue homeostasis, and thus, the dysregulated expression of lncRNAs is involved in the onset and progression of many pathological conditions. Research has indicated that the genetic knockout of some lncRNAs in mice resulted in peri- or postnatal lethality or developmental defects. Diabetes mellitus (DM) is a major cause of peripheral neuropathy. Our studies showed that the expression levels of lncRNA uc.48+ in the diabetic rat dorsal root ganglia (DRG) and the DM patients' serum samples were increased. It suggested that lncRNA uc.48+ was involved in the pathophysiological process of DM. The aim of this study was to investigate the effects of lncRNA uc.48+ small interfering RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X3 receptor in the DRG. The values of the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von Frey test and Hargreaves' test, respectively. The levels of P2X3 protein and messenger RNA (mRNA) in the DRG were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting. The experiments showed that the MWT and TWL values in DM rats were lower than those in the control rats. The MWT and TWL values in DM rats treated with lncRNA uc.48+ siRNA were increased compared to those in DM rats, but there was no significant difference between the DM rat group and the DM + scramble siRNA group. The levels of P2X3 protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X3 protein and mRNA in the DG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in DM rats. The expression levels of TNF-alpha in the DRG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in the DM group. The phosphorylation and activation of ERK1/2 in the DM DRG were decreased by uc.48+ siRNA treatment. Therefore, uc.48+ siRNA treatment may alleviate the DNP by inhibiting the excitatory transmission mediated by the P2X3 receptor in DRG. PMID- 26686230 TI - Toward the treatment for Alzheimer's disease: adsorption is primary mechanism of removing amyloid beta protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate. AB - The accumulation of amyloid beta protein (Abeta) in the brain reflects cognitive impairment in Alzheimer's disease. We hypothesized that the rapid removal of Abeta from the blood by an extracorporeal system may act as a peripheral Abeta sink from the brain. The present study aimed to determine the optimal materials and modality for Abeta removal by hemodialyzers. In a batch analysis, hollow fiber fragments of polysulfone (PSf) and polymethyl methacrylate (PMMA) showed greater removal efficiency of Abeta than did other materials, such as cellulose triacetates and ethylene-vinyl alcohol copolymer (PSf:PMMA at 30 min, 98.6 +/- 2.4 %:97.8 +/- 0.4 % for Abeta1-40 and 96.6 +/- 0.3 %:99.0 +/- 1.0 % for Abeta1 42). In a modality study, the Abeta solution was applied to PSf dialyzers and circulated in the dialysis and Air-filled adsorption-mode (i.e., the outer space of the hollow fibers was filled with air) or phosphate-buffered saline (PBS) filled adsorption modes. The Abeta1-40 removal efficiency of the pre/post dialyzer in the Air-filled adsorption-mode was the highest (62.4 +/- 12.6 %, p = 0.007). In a flow rate study in the Air-filled adsorption-mode, 200 mL/min showed the highest Abeta1-40 reduction rate of pool solution (97.3 +/- 0.8 % at 15 min) compared with 20 mL/min (p = 0.00001) and 50 mL/min (p = 0.00382). PMMA dialyzers showed similar high reduction rates. Thus, the optimal modality for Abeta removal was the adsorption-mode with PSf or PMMA hollow fibers at around 50 mL/min flow rate, which seems to be suitable for clinical use. PMID- 26686231 TI - Regulatory roles of biogenic amines and juvenile hormone in the reproductive behavior of the western tarnished plant bug (Lygus hesperus). AB - Mating induces behavioral and physiological changes in the plant bug Lygus hesperus Knight (Hemiptera: Miridae). After receiving seminal products, which include the systemic regulator juvenile hormone (JH), females enter a post-mating period lasting several days during which they enhance their oviposition rate and lose interest in remating. To elucidate the regulation of these behavioral changes in L. hesperus, biogenic amines were quantified in the heads of females at 5 min, 1 h and 24 h after copulation and compared to levels in virgins using high-performance liquid chromatography coupled with electrochemical detection. Mating significantly increased dopamine (DA) after 1 and 24 h, and decreased octopamine (OA) after 5 min and 1 h. Serotonin did not change with mating, but tyramine was significantly reduced after 5 min. While injection of amines into virgin females did not influence sexual receptivity, OA caused a decrease in oviposition during the 24 h following injection. Topical application of the JH analog methoprene to virgins caused an increase in DA, and a decline in mating propensity, but did not influence other amines or the oviposition rate. The results suggest the decline in OA observed immediately after mating may promote egg laying, and that male-derived JH may induce an increase in DA that could account for the post-mating loss of sexual receptivity. PMID- 26686232 TI - Effect of different culture media and deswelling agents on survival of human corneal endothelial and epithelial cells in vitro. AB - PURPOSE: To examine the effects of media and deswelling agents on human corneal endothelial and epithelial cell viability using a previously developed screening system. METHODS: The human corneal endothelial cell line HCEC-12 and the human corneal epithelial cell line HCE-T were cultured in four different corneal organ culture media (serum-supplemented: MEM +2 % FCS, CorneaMax(r)/CorneaJet(r), serum free: Human Endothelial-SFM, Stemalpha-2 and -3) with and without 6 % dextran T500 or 7 % HES 130/0.4. Standard growth media F99HCEC and DMEM/F12HCE-T served as controls. In additional controls, the stress inducers staurosporine or hydrogen peroxide were added. After 5 days in the test media, cell viability was assessed by flow cytometrically quantifying apoptotic and necrotic cells (sub-G1 DNA content, vital staining with YO-PRO-1(r) and propidium iodide) and intracellular reactive oxygen species (ROS). RESULTS: The MEM-based media were unable to support HCEC-12 and HCE-T survival under stress conditions, resulting in significantly increased numbers of apoptotic and necrotic cells. HCEC-12 survival was markedly improved in SFM-based media even under staurosporine or hydrogen peroxide. Likewise, HCE-T survival was improved in SFM with or without dextran. The media CorneaMax(r), CorneaJet(r), and CorneaMax(r) with HES supported HCEC-12 survival better than MEM-based media, but less well than SFM based media. HCE-T viability was also supported by CorneaJet(r), but not by CorneaMax(r) with or without HES. Stemalpha-based media were not suitable for maintaining viability of HCEC-12 or HCE-T in the applied cell culture system. CONCLUSIONS: The use of serum-supplemented MEM-based media for corneal organ culture should be discontinued in favour of serum-free media like SFM. PMID- 26686233 TI - Comparison of lateral orbital decompression with and without rim repositioning in thyroid eye disease. AB - PURPOSE: Rim-off lateral wall decompression may be associated with functional and cosmetic deficit. Our objective, therefore, was to describe the functional and cosmetic results of deep lateral orbital decompression with and without anterior rim repositioning for thyroid eye disease. METHODS: In this retrospective comparative case series all consecutive thyroid eye disease patients who underwent deep lateral wall decompression at the Royal Victorian Eye and Ear Hospital between 1990-2007 and the Goldschleger Eye Institute, Sheba Medical Center between 2008-2011 were included. Patients were divided into two groups: the "rim-on" group in which the anterior lateral orbital rim was repositioned and the "rim-off" group in which it was left off. Main outcome measures were: proptosis reduction, postoperative oscillopsia and diplopia, presence of visible or palpable lateral orbit depression. RESULTS: One hundred and twelve patients who underwent 186 orbital decompressions were included in the final analysis. The average proptosis reduction for two- and three-wall decompressions ranged between 4.6-4.9 mm in the rim-on and 4.6-5.7 mm in the rim-off group respectively. The prevalence of postoperative oscillopsia was similar in both groups. The preoperative diplopia worsened in 17 patients (32.1 %) in the rim-on group and in seven patients (12.3 %) in the rim-off group (P = .02, chi-square test). None of the patients developed visible or palpable lateral orbit depression. CONCLUSIONS: Deep lateral orbital decompression without anterior rim repositioning may be an effective approach to enhance functional and cosmetic outcomes in thyroid eye disease patients without increasing the risk of lateral wall depression or postoperative oscillopsia. PMID- 26686234 TI - Neurometabolic roles of ApoE and Ldl-R in mouse brain. AB - Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer's disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life. PMID- 26686235 TI - Relationship between spicy food intake and chronic uninvestigated dyspepsia in Iranian adults. AB - OBJECTIVE: To assess the association between spicy food consumption and chronic uninvestigated dyspepsia (CUD) in a large sample of Iranian adults. METHODS: In this cross-sectional study we assessed the consumption of spicy foods in 4763 Iranian adults living in Isfahan Province using a dietary habit questionnaire. A modified validated version of the Rome III questionnaire was used to assess CUD related symptoms. CUD was defined as having one or more of the following characteristics: distressing postprandial fullness, early satiation and/or epigastric pain or epigastric burning at least often during the past three months. Information on meal regularity, meal frequency, intra-meal intake of fluid as well as other potential confounders was also collected. RESULTS: CUD was prevalent in 15% of the participants. The frequent consumption of spicy foods (>= 10 times/week) was associated with greater odds of having CUD [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.09-2.49, P < 0.05). This relationship was significant even after adjusted for diet-related practices (OR 1.68, 95% CI 1.01 2.79, P < 0.05). There was a significantly positive association between spicy food consumption and postprandial fullness (OR 1.76, 95% CI 1.29-2.40, P < 0.05) and epigastric pain (OR 1.78, 95% CI 1.30-2.44, P < 0.05). However, no significant relationship was observed between the frequent consumption of spicy foods and early satiation. CONCLUSIONS: High consumption of spicy foods is associated with greater odds of CUD, frequent postprandial fullness and epigastric pain. Further studies, particularly of a prospective nature, are needed to confirm our findings. PMID- 26686237 TI - Access to aliphatic protons as reporters in non-deuterated proteins by solid state NMR. AB - Interactions within proteins, with their surrounding, and with other molecules are mediated mostly by hydrogen atoms. In fully protonated, inhomogeneous, or larger proteins, however, aliphatic proton shifts tend to show little dispersion despite fast Magic-Angle Spinning. 3D correlations dispersing aliphatic proton shifts by their better resolved amide N/H shifts can alleviate this problem. Using inverse second-order cross-polarization (iSOCP), we here introduce dedicated and improved means to sensitively link site-specific chemical shift information from aliphatic protons with a backbone amide resolution. Thus, even in cases where protein deuteration is impossible, this approach may enable access to various aspects of protein functions that are reported on by protons. PMID- 26686236 TI - Anti-depressant effects of phosphodiesterase 3 inhibitor cilostazol in chronic mild stress-treated mice after ischemic stroke. AB - RATIONALE: Phosphodiesterase 3 (PDE3) inhibitor cilostazol ameliorates negative effects of cerebral hypoperfusion against cerebral ischemic injury through the phosphodiesterase 3-cyclic adenosine monophosphate (cAMP) signaling cascade. OBJECTIVES: We investigated the question of whether cilostazol would have an anti depressant effect on chronic mild stress (CMS)-treated mice after ischemic stroke. METHODS: An animal model of post-stroke depression was developed by additional CMS procedures in middle cerebral artery occlusion (MCAO). We performed behavioral, histological, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, Western blot and enzyme linked immunosorbent assays (ELISA). RESULTS: In the open field, sucrose preference, forced swim and Morris water maze test, treatment with cilostazol resulted in reduction of all depressive behaviors examined, particularly in the Morris water maze test. Treatment with cilostazol reduced prominent atrophic changes in the ipsilateral striatum and hippocampus of CMS-treated ischemic mice through inhibition of neuronal cell death and microglial activation. In addition, treatment of the CMS-treated ischemic mice with cilostazol resulted in significantly increased phosphorylation of cAMP response element-binding protein (CREB) and expression of mature brain-derived neurotrophic factor (BDNF) with its receptor tropomyosin receptor kinase B (TrkB) in the ipsilateral striatum and hippocampus. Phosphorylation of CREB was also demonstrated in the dopaminergic neurons of the midbrain. Treatment with cilostazol also resulted in an increased number of newly formed cells and enhanced differentiation into neurons in the ipsilateral striatum and hippocampus. CONCLUSIONS: Our results suggest that phosphodiesterase 3 inhibitor cilostazol may have anti-depressant effects on post stroke depression through inhibition of neurodegeneration in the primary lesion and secondary extrafocal sites and promotion of neurogenesis. These beneficial effects on post-stroke depression may be involved in activation of CREB/BDNF signaling. PMID- 26686238 TI - Soft Tissue Reconstruction After Total Ankle Arthroplasty. AB - BACKGROUND: Wound complications following total ankle replacement (TAR) may potentially lead to devastating consequences. Soft tissue coverage of the prosthesis and tendons with a flap potentially prevent a catastrophic cascade leading to infection and implant failure. The aim of this study was to investigate the success and complications of flaps following soft tissue defects as a result of total ankle arthroplasty. METHODS: We retrospectively identified a consecutive series of 1001 primary TARs performed between January 1998 and December 2014 whose data were prospectively collected. We then identified patients who required a secondary surgery to treat soft tissue defects that were not amenable to split-thickness skin grafting. Clinical outcomes including secondary procedures, wound healing failure, complications, and implant failure rate were recorded. Nineteen patients had a total of 44 operative procedures to treat wound issues (1.9% of all prostheses). The follow-up time from the flap procedure is 24.1 months. RESULTS: More than two-thirds (13/19) of patients had 1 or more previous surgeries on the ankle, for an average of 1.2 procedures. The mean time to the flap procedure was 13.1 weeks after the index TAR. The most common reason for flap coverage was a non-healing anterior wound. Thirteen of 19 patients (68.4%) underwent formal operative wound exploration and debridement prior to their definitive flap coverage. The average size of the wound was 5.4 * 3.8 cm with an average area of 24.9 cm(2). The most common type of flap performed was a sural pedicle flap followed by a propeller flap. There were 4 flap failures (21.1%), with 2 subsequent below-the-knee amputations. No TAR patients developed a deep infection following a flap unless they had a preexisting infection. In patients who had a successful flap, there were significant improvements in their American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot, visual analog scale (VAS), and Short Musculoskeletal Function Assessment bother index, but not their Short Form-36 scores. CONCLUSION: Ankle wounds that occur after TAR can result in a devastating outcome, but management with a coordinated effort with surgeons with microvascular experience can help achieve salvage of the prosthesis. A variety of flap reconstruction options are available and should be employed to improve the rate of implant survival and retention. LEVEL OF EVIDENCE: Level IV, case series. PMID- 26686240 TI - Making C-H bonds with CO2: production of formate by molecular electrocatalysts. AB - Molecular approaches to the electrocatalytic reduction of CO2 to formate are varied and versatile in their methods. We discuss recent efforts to catalyse this reaction including significant progress made in the last 5 years. This Feature Article begins with a survey of molecular electrocatalysts that produce CO or H2, but have been observed under certain conditions to afford some formate. These examples are included because they provide valuable mechanistic insight for design of catalysts that produce hydrogenated products selectively from CO2. The subsequent discussion describes catalyst properties that favour C-H bond formation with CO2 and this is followed by recent advances that have been made in developing these catalysts. The focus on specific catalyst systems includes recently reported Ir PCP-type pincer complexes and Fe carbonyl clusters, such as [Fe4N(CO)12](-), that selectively produce formate from CO2 in aqueous solution. A discussion of the relevant thermochemical properties of the catalysts in the context of formate production is included. PMID- 26686241 TI - Hip strategy alterations in patients with history of low disc herniation and non specific low back pain measured by surface electromyography and balance platform. AB - PURPOSE: The appearance of pathology in the lumbar spine, such as a previous episode of low disc herniation or non-specific low back pain contributes to improper activation of the hip muscles. The aim of the study was to detect alterations in hip strategy manifested by differences in balance parameters and rectus femoris and gluteus maximus activity in people with previous episode of pain radiation to one lower limb caused by low disc herniation or non-specific low back pain. METHODS: We studied 11 patients with history of low-disc herniation, 9 patients with history of non-specific low back pain and 10 healthy subjects. Hip strategy alterations were detected by measuring rectus femoris and gluteus maximus activity in bilateral surface polyelectromyographic recordings and by stability measurements on a balance platform. RESULTS: In the surface polyelectromyography study, in both patients' group the value of the average amplitude was higher and the amount of the fluctuations was lower than in healthy subjects. There were no significant differences in stability parameters. CONCLUSIONS: A changed pattern of hip muscles activity was detected in the patients without changes in stability parameters. Greater disorder occurs in people in with previous episode of pain radiation to one lower limb caused by low disc herniation than in people with non-specific low back pain. PMID- 26686239 TI - GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation. AB - BACKGROUND: Combinations of reflux parameters (acid exposure time, AET; symptom association probability, SAP) on pH-impedance monitoring describe varying confidence in reflux evidence. We compared outcomes between phenotypes with distinct pre-identified reflux parameters. METHODS: In this observational cohort study, patients undergoing pH-impedance testing over a 5-year period were phenotyped by strength of reflux evidence as strong (abnormal AET, positive SAP), good (abnormal AET, negative SAP), reflux hypersensitivity (RH, normal AET, positive SAP), and equivocal evidence of reflux, and compared to two historical institutional pH monitoring cohorts. Symptom burden (dominant symptom intensity, DSI; global symptom severity, GSS) was assessed by questionnaire at baseline and on prospective follow-up and compared between phenotypes. KEY RESULTS: Of 94 patients tested off proton pump inhibitor (PPI) therapy, baseline symptom burden was highest with strong reflux evidence and lowest when equivocal (DSI: p = 0.01; GSS: p = 0.03 across groups). After 3.1 +/- 0.2 years follow-up, symptomatic improvement with surgical or medical therapy was highest with strong or good evidence, and lowest when equivocal (DSI: p = 0.008; GSS: p = 0.005 across groups). This was most pronounced for typical symptoms (DSI: p = 0.001; GSS: 0.016 across groups), but not atypical symptoms (DSI: p = 0.6; GSS: p = 0.2). For testing on PPI therapy, only GSS followed a similar trend (GSS: p = 0.057, DSI: p = 0.3). Compared to historical cohorts with pH monitoring alone, equivocal evidence for reflux was partly replaced by RH, especially off PPI (p < 0.0001). CONCLUSIONS & INFERENCES: Phenotyping gastroesophageal reflux disease by the strength of reflux evidence on pH-impedance testing off PPI efficiently stratifies symptomatic outcome, especially for typical symptoms, and could be useful in planning management. PMID- 26686242 TI - Novel superhard B-C-O phases predicted from first principles. AB - We explored the B-C-O system at pressures in the range 0-50 GPa by ab initio variable-composition evolutionary simulations in the hope of discovering new stable superhard materials. A new tetragonal thermodynamically stable phase B4CO4, space group I4[combining macron], and two low-enthalpy metastable compounds (B6C2O5, B2CO2) have been discovered. Computed phonons and elastic constants show that these structures are dynamically and mechanically stable both at high pressure and zero pressure. B4CO4 is thermodynamically stable at pressures above 23 GPa, but should remain metastable under ambient conditions. Its computed hardness is about 38-41 GPa, which suggests that B4CO4 is potentially superhard. PMID- 26686243 TI - In Situ Click Chemistry for the Identification of a Potent D-Amino Acid Oxidase Inhibitor. AB - In situ click chemistry is a target-guided synthesis approach for discovering novel lead compounds by assembling organic azides and alkynes into triazoles inside the affinity site of target biogenic molecules such as proteins. We report in situ click chemistry screening with human D-amino acid oxidase (hDAO), which led to the identification of a more potent hDAO inhibitor. The hDAO inhibitors have chemotherapeutic potential as antipsychotic agents. The new inhibitor displayed competitive inhibition of hDAO and showed significantly increased inhibitory activity against hDAO compared with that of an anchor molecule of in situ click chemistry. PMID- 26686244 TI - Synthesis of 3-Deoxy-L-ketohexoses through Group Transfer. AB - A practical method for the synthesis of 3-deoxy-L-ketohexoses is described. Both D- and L-ketohexoses can be transformed into rare 3-deoxy-L-ketohexoses in six steps through a group transfer process. The key step involves a radical cyclized onto a carbonyl group, followed by a fragmentation reaction, eventually resulting in the group transfer of an alpha-oxy carbonyl group. The process involves tin free and environmentally benign radical conditions (TTMSS/AIBN/toluene). The acyclic form of 3-deoxy-L-fructose was prepared in only three steps from the inexpensive starting material, D-fructose. A further modification by preparing a dithioacetal derivative was accomplished, which could serve as a convenient sugar synthon for further synthetic applications. Removal of the dithioacetal protecting group results in the formation of the rare 3-deoxy-L-fructose in a total yield of 42%. This methodology could be further extended to the synthesis of other deoxy-L-ketohesoses, such as 3-deoxy-L-sorbose. PMID- 26686246 TI - Next-generation IgVH sequencing CLL-like monoclonal B-cell lymphocytosis reveals frequent oligoclonality and ongoing hypermutation. AB - Chronic lymphocytic leukemia (CLL) develops from CLL-like monoclonal B-cell lymphocytosis (MBL) which represents a low-level asymptomatic expansion of cells that phenotypically resemble CLL. Although antigen selection plays a key role during CLL development, it is not known whether this occurs in early MBL or only during progression to CLL. Recent studies suggested that MBL sometimes displays oligoclonality, but these used techniques with limited sensitivity and specificity and were not conclusive. In this study, we combine cell sorting and next-generation sequencing of rearranged immunoglobulin heavy chain variable (IgVH) genes to thoroughly assess the VH repertoire and oligoclonality of purified MBL cells. Clonal functional rearrangements or clonotypes were identified in 29 of 30 sequenced cases, with 7 or 24% having two clonotypes with unrelated CDR3 sequences. In four of the seven cases with unrelated clonotypes, VH segments from the same family were used. In addition, 6 of 29 cases showed clear evidence of ongoing VH gene hypermutation with three of these being among the seven with unrelated clonotypes. This study conclusively shows that MBL cases often contain multiple B-cell clones, the first to report ongoing VH gene mutation in MBL, and that antigen selection appears to occur in early MBL. PMID- 26686245 TI - The combination of FLT3 and DNA methyltransferase inhibition is synergistically cytotoxic to FLT3/ITD acute myeloid leukemia cells. AB - Effective treatment regimens for elderly acute myeloid leukemia (AML) patients harboring internal tandem duplication mutations in the FMS-like tyrosine kinase-3 (FLT3) gene (FLT3/ITD) are lacking and represent a significant unmet need. Recent data on the effects of FLT3 tyrosine kinase inhibitors on FLT3/ITD(+) AML showed promising clinical activity, including in elderly patients. DNA methyltransferase (DNMT) inhibitors such as decitabine (5-aza-2-deoxycytidine, DEC) and 5 azacitidine (AZA) demonstrated clinical benefit in AML, are well tolerated and are associated with minimal increases in FLT3 ligand, which can represent a potential resistance mechanism to FLT3 inhibitors. In addition, both FLT3 and DNMT inhibition are associated with the induction of terminal differentiation of myeloid blasts. Consequently, there is a strong theoretical rationale for combining FLT3 and DNMT inhibition for FLT3/ITD(+) AML. We therefore sought to study the anti-leukemic effects of DEC, AZA and FLT3 inhibitors, either as single agents or in combination, on AML cell lines and primary cells derived from newly diagnosed and relapsed AML patients. Our studies indicate that combined treatment using FLT3 inhibition and hypomethylation confers synergistic anti-leukemic effects, including apoptosis, growth inhibition and differentiation. The simultaneous administration of AZA and FLT3 inhibition appears to be the most efficacious combination in this regard. These drugs may provide a novel therapeutic approach for FLT3/ITD(+) AML, in particular for older patients. PMID- 26686247 TI - Low incidence of peripheral arterial disease in patients receiving dasatinib in clinical trials. PMID- 26686249 TI - Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. AB - BACKGROUND: Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. OBJECTIVE: To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF kappaB) and nuclear factor-erythroid-related factor-2 (Nrf2). METHODS: Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-kappaB and Nrf2 expression levels were assayed through immunohistochemistry. RESULTS: Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-kappaB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-kappaB expression. CONCLUSION: The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-kappaB. PMID- 26686248 TI - The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models. AB - The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B cell marker B220, and had clonal B-cell receptor rearrangements. Using whole exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia. PMID- 26686250 TI - Systemic treatment of patients with metachronous peritoneal carcinomatosis of colorectal origin. AB - Combining chemotherapy and targeted therapies has resulted in an enhanced survival in metastatic colorectal cancer (mCRC) patients. However, the result of this palliative treatment in patients with metachronous peritoneal carcinomatosis (PC) remains unknown. The current population-based study aims to investigate the use and effect of palliative systemic treatment in patients with metachronous PC of colorectal origin. Data on metachronous PC were collected between 2010 and 2011 for all patients who were diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Patient demographics and detailed data on chemotherapeutic treatment were collected and compared. Ninety two patients with metachronous PC received chemotherapy in a palliative setting compared to 94 patients without treatment. In 36 patients, Bevacizumab was added to the treatment (39%). Overall survival was 3.4, 13, and 20.3 months in the no treatment, systemic treatment and systemic treatment + Bevacizumab respectively (P < 0.001). Male gender was a positive predictor and right sided primary tumor location a negative predictor of receiving bevacizumab. Approximately 40% of patients with metachronous PC received bevacizumab in addition to chemotherapy. Treatment with systemic chemotherapy in combination with bevacizumab may increase survival in a patients with metachronous colorectal PC. PMID- 26686251 TI - The rising cost of orphan drugs. PMID- 26686252 TI - Thalidomide for hereditary haemorrhagic telangiectasia. PMID- 26686253 TI - Limits of registry data to understand survival disparities in lymphoma. PMID- 26686254 TI - Cardiovascular disease after Hodgkin's lymphoma: a role for screening. PMID- 26686256 TI - Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study. AB - BACKGROUND: Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. METHODS: We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. FINDINGS: Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15.9 months (IQR 10.1-22.3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74 98) patients had partial responses. Overall, all 31 (100%, 89-100) patients responded to therapy with a significant decrease in all epistaxis parameters (p<0.0001 for frequency, intensity, and duration). A response was achieved by 25 (81%) patients at 50 mg/day of thalidomide, five (16%) patients at 100 mg/day, and one (3%) patient at 150 mg/day. Patients had only non-serious, grade 1 adverse effects, the most common of which were constipation (21 patients), drowsiness (six patients), and peripheral oedema (eight patients). One patient died a month after the end of treatment, but this was not deemed to be related to treatment. INTERPRETATION: Low-dose thalidomide seems to be safe and effective for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia. Our findings should be validated by further studies with larger patient populations, longer follow-up, and that also assess the benefit for quality of life. FUNDING: Telethon Foundation. PMID- 26686257 TI - Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study. AB - BACKGROUND: Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis (DVT) of the legs. Compression ultrasonography can be extended to the entire deep venous system (whole-leg) or restricted to the proximal veins only (limited), and the two approaches are clinically equivalent. We aimed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography. METHODS: We did a prospective, multicentre, cohort study at eight centres in five countries. Consecutive outpatients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment. DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative (group 1). Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only (group 2). Finally, patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography (group 3). All patients in whom DVT was ruled out were followed up for 3 months. The primary outcome was the incidence of objectively recorded venous thromboembolism. The primary analysis included all patients managed according to the study protocol. This study is registered with ClinicalTrials.gov, number NCT01412242. The final results are reported here. FINDINGS: Between March 1, 2011, and July 31, 2014, 1348 consecutive outpatients were referred for this study, of whom 1162 were eligible to participate. After pretest probability assessment and D-dimer testing, 351 were in group 1, 401 in group 2, and 410 in group 3. Limited compression ultrasonography was positive in 12 (3%) patients in group 2 and extended whole leg compression ultrasonography was positive in 200 (49%) patients in group 3. 82 (39%) of all DVT diagnosed at baseline were isolated distal thromboses. 26 protocol violations were reported. Thus, 351 patients from group 1, 371 patients in group 2, and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months. One, four, and three DVTs were reported, respectively. Thus, the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0.87% (95% CI 0.44-1.70). INTERPRETATION: An algorithm combining limited and whole-leg compression ultrasonography could be a reliable, safe, and convenient method for diagnostic management of outpatients with clinically suspected DVT. FUNDING: None. PMID- 26686259 TI - Cardiovascular disease after treatment for Hodgkin's lymphoma: an analysis of nine collaborative EORTC-LYSA trials. AB - BACKGROUND: Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. METHODS: In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. FINDINGS: Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1.015 [95% CI 1.006-1.024], p=0.0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1.077 [1.021-1.137], p=0.0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0.77), vincristine (p=0.36), and mean radiation dose to the left (p=0.41) or right (p=0.70) internal carotid artery did not predict for cardiovascular events. INTERPRETATION: Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients. FUNDING: Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship. PMID- 26686260 TI - Patients' reluctance to undergo deep brain stimulation for Parkinson's disease. AB - BACKGROUND: Many patients with advanced Parkinson's disease (PD) are reluctant to undergo the subthalamic nucleus deep brain stimulation (STN-DBS) when surgery is warranted. Reasons for this reluctance have not been examined. We undertook to establish the rate and causes of this reluctance for STN-DBS in patients with advanced PD. METHODS: A reluctant group was defined as patients who were hesitant to undergo DBS. Clinical information included age, onset age, disease duration, the Unified Parkinson Disease Rating Scale, Hoehn and Yahr stage and levodopa equivalent dose when they were evaluated with a view to consider surgery. RESULTS: We enrolled 186 patients who underwent STN-DBS. 84 patients (45%) belonged to the reluctant group. Between the reluctant and the non-reluctant, there were no differences in preoperative characteristics. Main reasons for hesitation were fear of complications (74%) and economic burden (50%). The main reasons that they finally underwent the DBS were confidence in the doctor's decision (80%) and encouragement from their family (36%). CONCLUSIONS: Building trust between patients and physicians is an important factor in guiding patients to undergo this treatment. To reduce the reluctance to undergo DBS at the appropriate time, we need to find effective ways of reducing their psychological and economic burden. PMID- 26686258 TI - Changes in dynamics of excess mortality rates and net survival after diagnosis of follicular lymphoma or diffuse large B-cell lymphoma: comparison between European population-based data (EUROCARE-5). AB - BACKGROUND: Since 2001, the World Health Organization classification of tumours of haematopoietic and lymphoid tissues and the International Classification of Diseases for Oncology (third edition) have improved data collection for lymphoma subtypes in most European cancer registries and allowed reporting on the major non-Hodgkin lymphoma subtypes. Treatment of non-Hodgkin lymphoma has changed profoundly, benefiting patients with follicular lymphoma or diffuse large B-cell lymphoma. We aimed to compare dynamics of cancer mortality in patients with follicular lymphoma or diffuse large B-cell lymphoma in five large European areas using data for survival from the largest number of collaborative European population-based cancer registries (EUROCARE). METHODS: We considered follicular lymphoma and diffuse large B-cell lymphoma cases in patients aged older than 15 years diagnosed between Jan 1, 1996, and Dec 31, 2004, and recorded in 43 cancer registries in five areas: Scotland and Wales, and northern, central, eastern, and southern Europe. We excluded cases incidentally diagnosed at autopsy or known from death certificates only. The vital status could be updated on Dec 31, 2008, in all registries but the French ones (Dec 31, 2007). We obtained changes in net survival with the Pohar-Perme estimator and excess mortality rate with a flexible parametric model according to age and year of diagnosis. FINDINGS: We identified 13,988 follicular lymphoma and 25,320 diffuse large B-cell lymphoma cases. We noted improvements in 5-year net survival for all ages between the 1999-2001 and 2002-04 periods for both cancers (except for follicular lymphoma in Scotland and Wales and diffuse large B-cell lymphoma in eastern Europe). For follicular lymphoma, 5-year net survival in northern Europe was 64% (95% CI 58-71) in 1999 2001 versus 75% (69-80) for 2002-04, for Scotland and Wales, it was 71% (66-76) versus 68% (64-72), for central Europe, it was 64% (61-67) versus 72% (70-75), for southern Europe, it was 67% (63-70) versus 73% (70-76), and for eastern Europe, it was 50% (43-57) versus 61% (54-69). For diffuse large B-cell lymphoma, 5-year net survival in northern Europe was 41% (35-49) versus 58% (54-62), in Scotland and Wales, it was 44% (41-48) versus 52% (49-54), in central Europe, it was 46% (44-47) versus 50% (48-51), in southern Europe, it was 44% (42-47) versus 50% (48-52), and in eastern Europe, it was 47% (41-54) versus 46% (43-50). We noted the largest area disparity during the 2002-04 period between eastern and northern Europe. We noted a significant effect of the year of diagnosis on the excess mortality rate for all ages in all areas, except for diffuse large B-cell lymphoma in eastern Europe. The excess mortality rate was not constant during the follow-up period: we noted a high rate early for both lymphomas, except for follicular lymphoma in northern Europe. INTERPRETATION: Although survival for follicular lymphoma and diffuse large B-cell lymphoma is improving, the results from this study should foster the search for more and better means of improvement of access to adequate care than that at present, as there remains variation in survival between European regions. Study of the dynamics of the excess mortality rate seems to be a useful clinical indicator to help the practitioner's choice of optimum management of patients. FUNDING: Compagnia di San Paolo, Fondazione Cariplo Italy, Italian Ministry of Health, European Commission, Registre des Hemopathies Malignes de Cote d'Or, and French Agence Nationale de la Recherche. PMID- 26686261 TI - SCAI/ACC/HRS Institutional and Operator Requirements for Left Atrial Appendage Occlusion. PMID- 26686262 TI - Improving Adolescent Pelvic Inflammatory Disease Follow-up From the Emergency Department: Randomized Controlled Trial With Text Messages. AB - STUDY OBJECTIVE: Centers for Disease Control and Prevention guidelines recommend follow-up within 72 hours of diagnosis of pelvic inflammatory disease because patients with inadequate treatment are at increased risk of acute and chronic complications. Follow-up rates in adolescents after diagnosis range between 10% and 16%. The primary objective is to assess the effect of text message reminders to adolescent patients receiving a diagnosis of pelvic inflammatory disease on obtaining follow-up care within 72 hours of emergency department (ED) discharge. METHODS: This was a single-blinded randomized controlled trial of adolescents receiving a diagnosis of pelvic inflammatory disease in the ED. Patients received standard discharge instructions or standard discharge instructions plus text message reminders. Patients in the text message group received daily, tailored text messages for 4 days, with a reminder to schedule and attend primary care provider follow-up. The primary outcome was follow-up within 72 hours of ED discharge. RESULTS: Ninety-five patients (48 standard; 47 text message) were randomized. Three patients were excluded, leaving 92 patients (46 standard; 46 text message) for analysis. Baseline characteristics were similar between treatment groups. Follow-up was 15.2% in the standard group and 43.5% in the text message group. Patients receiving text message reminders were more likely to follow up compared with the standard group (relative risk 2.9; 95% confidence interval [CI] 1.4 to 5.7). The absolute efficacy difference was 28.3% (95% CI 9.5% to 46.9%), yielding number needed to treat of 4 (95% CI 2.2 to 9.5). CONCLUSION: Personalized text message reminders were efficacious in improving follow-up for adolescents after ED diagnosis of pelvic inflammatory disease. PMID- 26686263 TI - Enzymatic cellulose oxidation is linked to lignin by long-range electron transfer. AB - Enzymatic oxidation of cell wall polysaccharides by lytic polysaccharide monooxygenases (LPMOs) plays a pivotal role in the degradation of plant biomass. While experiments have shown that LPMOs are copper dependent enzymes requiring an electron donor, the mechanism and origin of the electron supply in biological systems are only partly understood. We show here that insoluble high molecular weight lignin functions as a reservoir of electrons facilitating LPMO activity. The electrons are donated to the enzyme by long-range electron transfer involving soluble low molecular weight lignins present in plant cell walls. Electron transfer was confirmed by electron paramagnetic resonance spectroscopy showing that LPMO activity on cellulose changes the level of unpaired electrons in the lignin. The discovery of a long-range electron transfer mechanism links the biodegradation of cellulose and lignin and sheds new light on how oxidative enzymes present in plant degraders may act in concert. PMID- 26686264 TI - Impact of education on clinicians' attitudes to exposure therapy for eating disorders. AB - It is well established that clinicians use exposure therapy far less often than the evidence would suggest is justified. This shortfall has been explained as being at least partly a result of clinicians' beliefs and attitudes about exposure and their trait anxiety. Recent studies have shown that attitudes to exposure therapy for anxiety disorders can be improved through a simple educational approach. This study aimed to determine whether a similar educational approach can improve therapists' attitudes to exposure therapy for the eating disorders, and whether clinician's pre-intervention characteristics influenced the impact of the training. Thirty-four eating disorder clinicians (30 female, four male; mean age = 39.0 years; 85.3% Caucasian) attended a 90-min didactic teaching session on the subject of the use of exposure in treatment of eating disorders. Their attitudes to exposure therapy were measured before and after the workshop, in a within-subject design. The outcome was a substantial improvement in attitudes, with a strong effect size (Cohen's d = 1.68) that was comparable to the outcome of a similar intervention among clinicians working with anxiety disorders. The improvement was not related to clinicians' anxiety levels, but was greater among those whose attitudes were more negative at the outset of the teaching. While this finding needs to be tested for long-term maintenance and its relationship to change in clinical practice, it adds to the evidence that a simple educational intervention is sufficient to result in substantial improvement in clinicians' attitudes to exposure therapy. PMID- 26686265 TI - Testing the dependence of stabilizing effect of osmolytes on the fractional increase in the accessible surface area on thermal and chemical denaturations of proteins. AB - Here we have generated two different denatured states using heat- and guanidinium chloride (GdmCl)-induced denaturations of three disulfide bond free proteins (barstar, cytochrome-c and myoglobin). We have observed that these two denatured states of barstar and myoglobin are structurally and energetically different, for, heat-induced denatured state contains many un-melted residual structure that has a significant amount of secondary and tertiary interactions. We show that structural properties of the denatured state determine the magnitude of the protein stabilization in terms of Gibbs free energy change (DeltaGD degrees ) induced by an osmolyte, i.e., the greater the exposed surface area, the greater is the stabilization. Furthermore, we predicted the m-values (ability of osmolyte to fold or unfold proteins) using Tanford's transfer-free energy model for the transfer of proteins to osmolyte solutions. We observed that, for each protein, m value is comparable with our experimental data in cases of TMAO (trimethylamine-N oxide) and sarcosine. However, a significant discrepancy between predicted and experimental m-values were observed in the case of glycine-betaine. PMID- 26686266 TI - Use of smartphone technology in cardiology. AB - Smartphone-based technologies along with broadband connectivity are changing the way modern cardiology is practiced. The ever broadening connectivity and increasing capabilities of smartphone-based technologies can better monitor, diagnose, and prevent cardiovascular diseases. Researchers can leverage the ubiquitous use of smartphone-based technologies and their constant stream of biometric data to establish large community-based clinical research studies. Patient engagement is enhanced with constant and on-demand access to physicians, daily self-monitoring, and expanding social networks. On the other hand, the exponential growth of smartphone-based technologies invariably disrupts the traditional healthcare model and leaves a vacuum in the infrastructure, medico legal apparatus, and reimbursement systems that need to be addressed. In this review, we present a comprehensive discussion of the various applications utilizing smartphone-based technologies in cardiology. PMID- 26686267 TI - Patients' experience of Chinese Medicine Primary Care Services: Implications on Improving Coordination and Continuity of Care. AB - Chinese medicine (CM) is major form of traditional and complementary medicine used by Chinese populations. Evaluation on patients' experience on CM service is essential for improving service quality. This cross sectional study aims (i) to assess how CM clinics with different administrative model differ in terms of quality from patients' perspective; and (ii) to investigate how quality varies with patients' demographic and health characteristics. Five hundred and sixteen patients were sampled from charity and semi-public CM clinics in Hong Kong, and were invited to assess their experience using the Primary Care Assessment Tool (PCAT). Results indicated that overall mean PCAT scoring is satisfactory, achieving 70.7% (91.26/129) of total score. Ratings were lower in areas of "coordination of patient information", "continuity of care", and "range of service provided". Impact of administrative models, including involvement of tax funded healthcare system and outreach delivery, were minimal after adjusting for patient characteristics. Demographic and health characteristics of patients did not contribute to substantial variations in scoring. To improve patient experience, policy makers should consider strengthening care coordination, continuity and comprehensiveness in CM primary care services. Sharing of electronic records and establishing referral system are potential solutions for linking CM and conventional healthcare services. PMID- 26686268 TI - High-Performance Lithium-Sulfur Batteries with a Self-Assembled Multiwall Carbon Nanotube Interlayer and a Robust Electrode-Electrolyte Interface. AB - Elemental sulfur electrode has a huge advantage in terms of charge-storage capacity. However, the lack of electrical conductivity results in poor electrochemical utilization of sulfur and performance. This problem has been overcome to some extent previously by using a bare multiwall carbon nanotube (MWCNT) paper interlayer between the sulfur cathode and the polymeric separator, resulting in good electron transport and adsorption of dissolved polysulfides. To advance the interlayer concept further, we present here a self-assembled MWCNT interlayer fabricated by a facile, low-cost process. The Li-S cells fabricated with the self-assembled MWCNT interlayer and a high loading of 3 mg cm(-2) sulfur exhibit a first discharge specific capacity of 1112 mAh g(-1) at 0.1 C rate and retain 95.8% of the capacity at 0.5 C rate after 100 cycles as the self-assembled MWCNT interlayer facilitates good interfacial contact between the interlayer and the sulfur cathode and fast electron and lithium-ion transport while trapping and reutilizing the migrating polysulfides. The approach presented here has the potential to advance the commercialization feasibility of the Li-S batteries. PMID- 26686269 TI - Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats. AB - BACKGROUND & AIMS: Increased hepatic vascular resistance due to fibrosis and elevated hepatic vascular tone is the primary factor in the development of portal hypertension. Heparin may decrease fibrosis by inhibiting intrahepatic microthrombosis and thrombin-mediated hepatic stellate cell activation. In addition, heparin enhances eNOS activity, which may reduce hepatic vascular tone. Our study aimed at evaluating the effects of acute, short-, long-term and preventive enoxaparin administration on hepatic and systemic hemodynamics, liver fibrosis and nitric oxide availability in cirrhotic rats. METHODS: Enoxaparin (1.8 mg/kg subcutaneously), or its vehicle, was administered to CCl4-cirrhotic rats 24h and 1h before the study (acute), daily for 1 week (short-term) or daily for 3 weeks (long-term) and to thioacetamide-cirrhotic rats daily for 3 weeks with/without thioacetamide (preventive/long-term, respectively). Mean arterial pressure, portal pressure, portal blood flow, hepatic vascular resistance and molecular/cellular mechanisms were evaluated. RESULTS: No significant changes in hemodynamic parameters were observed in acute administration. However, one-week, three-week and preventive treatments significantly decreased portal pressure mainly due to a decrease in hepatic vascular resistance without significant changes in mean arterial pressure. These findings were associated with significant reductions in liver fibrosis, hepatic stellate cell activation, and desmin expression. Moreover, a reduction in fibrin deposition was observed in enoxaparin-treated rats, suggesting reduced intrahepatic microthrombosis. CONCLUSION: Enoxaparin reduces portal pressure in cirrhotic rats by improving the structural component of increased liver resistance. These findings describe the potentially beneficial effects of enoxaparin beyond the treatment/prevention of portal vein thrombosis in cirrhosis, which deserve further investigation. PMID- 26686270 TI - Gut-liver immunity. AB - The liver contributes to immune surveillance against pathogens entering via the gut and is itself influenced by alterations in mucosal immune responses and the microbiome. Mucosal immunity is also implicated in autoimmune liver diseases that associate with inflammatory bowel disease (IBD), and in steatohepatitis where compromised enteric barrier function and altered bacterial sensing drive liver inflammation. In this article, we discuss recent advances in our understanding of how dysregulated mucosal immune responses result in hepatobiliary injury; specifically through defective intestinal barrier function, changes in the enteric microbiome and loss of immune tolerance, and via shared leucocyte recruitment pathways. PMID- 26686271 TI - Introduction. PMID- 26686272 TI - Can procalcitonin monitoring reduce the length of antibiotic treatment in bloodstream infections? AB - Antibiotic overconsumption and subsequent bacterial multidrug resistance are associated with increased mortality, length of hospitalisation and healthcare costs. Discontinuation of antibiotic treatment in severe infections, such as bloodstream infections (BSIs), is a demanding clinical decision. In this review, we aim to investigate the usefulness of procalcitonin (PCT) monitoring in guiding appropriate treatment duration in BSIs and its impact on clinical outcomes. Data from clinical studies conducted after 2005 that included patients with BSIs indicate that change of PCT is an early indicator for prognosis in terms of survival and, overall, support the usefulness of a PCT-guided clinical algorithm in reducing the duration of antibiotic treatment without compromising survival. Furthermore, the presented data indicate that PCT assessment is helpful in the diagnosis of infective endocarditis. In conclusion, monitoring of PCT together with evaluation of the clinical situation is a valuable tool in reducing the length of antimicrobial treatment in BSIs. PMID- 26686273 TI - The role of probiotics in the prevention of severe infections following abdominal surgery. AB - Administration of probiotics has been proposed for various medical and surgical conditions. Their effect has been largely attributed to their ability to maintain the integrity of the intestinal mucosal barrier as well as to modulate the innate immune response. Multiple studies have demonstrated their effect in reducing infectious complications in critically ill patients, minimising bacterial translocation and increasing the secretion of anti-inflammatory cytokines. Furthermore, they have been shown to be effective in reducing infections following colorectal surgery, while at the same time preventing overgrowth of bacterial species such as Pseudomonas aeruginosa that has been implicated in the pathogenesis of anastomotic leak. Recent experimental studies have demonstrated that probiotics may decrease expression of the SOCS3 gene, which encodes the protein SOCS3 that suppresses cytokine production, implying a direct interaction of probiotics with the innate immune system. These results hold high promises for the development of new therapeutic strategies. PMID- 26686274 TI - The Thuringian registry for bloodstream infections, antibiotic resistance and the practice of blood culture sampling--AlertsNet. AB - Evidence-based blood culture (BC) testing is of utmost importance for intensive care unit (ICU) patients suspected for sepsis. Knowledge of the aetiological agent and its susceptibility to anti-infective agents enables the clinician to initiate appropriate antimicrobial therapy and guides diagnostic procedures. This has been shown to reduce mortality, ICU stay and antibiotic overuse. Whereas microbiological laboratory practice has been highly standardised, shortfalls in pre-analytic procedures in the ICU have a significant effect on the diagnostic yield. Currently, surveillance data on BC practice lack hospital-, patient- and laboratory-based denominator data. Supporting information on differences in the clinical practice of BC testing, differences in the characteristics of the institution and the case-mix on specific wards, as well as differences in the availability of microbiological laboratories is demanded on a population basis. A population-based survey on BC practice has been established for the German Federal State of Thuringia connecting both hospitals and microbiological laboratories within an electronic registry for immediate enrolment of BC findings (AlertsNet; http://www.alertsnet.de). The registry includes microbiological results and clinical data as well as institutional variables (e.g. case severity indices) from all patients with clinically relevant positive BCs at the participating centres. The main objectives are to sustain and expand a population based surveillance and warning system for the assessment of diagnosis, risk factors, treatment and outcomes of hospitalised patients and to improve outcomes of patients with bloodstream infections. PMID- 26686275 TI - Performance pressure and caffeine both affect cognitive performance, but likely through independent mechanisms. AB - A prevalent combination in daily life, performance pressure and caffeine intake have both been shown to impact people's cognitive performance. Here, we examined the possibility that pressure and caffeine affect cognitive performance via a shared pathway. In an experiment, participants performed a modular arithmetic task. Performance pressure and caffeine intake were orthogonally manipulated. Findings indicated that pressure and caffeine both negatively impacted performance. However, (a) pressure vs. caffeine affected performance on different trial types, and (b) there was no hint of an interactive effect. So, though the evidence is indirect, findings suggest that pressure and caffeine shape performance via distinct mechanisms, rather than a shared one. PMID- 26686276 TI - Efficient photolytic C-H bond functionalization of alkylbenzene with hypervalent iodine(iii) reagent. AB - A practical approach to radical C-H bond functionalization by the photolysis of a hypervalent iodine(iii) reagent is presented. The photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the generation of trifluoroacetoxy radicals, which allows the smooth transformation of various alkylbenzenes to the corresponding benzyl ester compounds under mild reaction conditions. PMID- 26686277 TI - Trends in registered medical marijuana participation across 13 US states and District of Columbia. AB - BACKGROUND: Medical marijuana (MMJ) laws and policies have evolved rapidly over the past decade in the United States. Public health concerns over the impact of these laws might be influenced by the degree of MMJ participation, but little is known about changes to this population over time. Trends in registered MMJ participation are described for 13 states in the US and District of Columbia (DC) since 2001. METHODS: Numbers of MMJ participants were obtained from state MMJ patient registries. A subset of states reported differences by sex and age. Prevalence of MMJ participation per 1000 was calculated. Data from California and Washington were not available. RESULTS: MMJ participation was relatively low and flat from 2001 to 2008 (i.e., less than 5 per 1000 adults). Participation rose sharply in Colorado, Montana, and Michigan in 2009-2010, but not for other states. High rates can currently be found in Colorado, Oregon, and Montana (i.e., 15-30 per 1000) with the national average around 7.6 per 1000 adults. Two-thirds of participants are male, but sex differences may be decreasing over time. Less than 1% of MMJ registrants are under 18, but this segment is growing in Colorado and Oregon. Participants tend to be older (50s), but Colorado and Arizona have larger proportions of young adult (21-30) registrants. CONCLUSIONS: Participation in MMJ programs varies considerably by state and within states over time. Trends are discussed within the context of federal and state policies, and the availability of marijuana via dispensaries. PMID- 26686278 TI - The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7) in the nucleus tractus solitarii of rats. AB - Angiotensin-1-7 [Ang-(1-7)], acting via the Mas receptor in the central nervous system, is involved in the regulation of cardiovascular activity. Nitric oxide (NO) is implicated as an important modulator in the nucleus tractus solitarii (NTS), a key region involved in control of cardiovascular activity. The aim of the present study was to determine the role of phosphatidylinositol 3-kinase (PI3K) signaling in mediating the effect of Ang-(1-7) on NO generation in the NTS. In Sprague-Dawley rats, acute injection of Ang-(1-7) into the NTS significantly increased NO generation and neuronal/endothelial NO synthase (n/eNOS) activity, which were abolished by the selective Mas receptor antagonist d-Alanine-[Ang-(1-7)] (A-779), the PI3K inhibitor LY294002, or the Akt inhibitor triciribine (TCN). Western blotting analysis further demonstrated that Ang-(1-7) significantly increased levels of Akt/NOS phosphorylation in the NTS, and Ang-(1 7)-induced e/nNOS phosphorylation was antagonized by LY294002 or TCN. Furthermore, gene knockdown of PI3K by lentivirus containing small hairpin RNA in the NTS prevented the Ang-(1-7)-induced increases in NOS/Akt phosphorylation and NO production. The physiological (in vivo) experiments showed that pretreatment with the NOS inhibitor l-NAME, LY294002, or TCN abolished the decreases in blood pressure, heart rate, and renal sympathetic nerve activity induced by Ang-(1-7) injected into the NTS. Our findings suggest that nitric oxide release meditated by the Mas-PI3K-NOS signaling pathway is involved in the cardiovascular effects of Ang-(1-7) in the NTS. PMID- 26686279 TI - [Tibiotalocalcaneal arthrodesis using a humeral locking plate]. AB - OBJECTIVE: To describe the results of tibiotalocalcaneal arthrodesis (TTC) using a humeral locking plate. METHODS AND MATERIALS: A retrospective, observational study was conducted between January 2007 and December 2013 in the Hospital Militar Central de Bogota. The study included patients with symptomatic osteoarthritis diagnosed clinically and radiologically, and who underwent TTC arthrodesis using a humeral locking plate with a minimum follow up of 6 months. RESULTS: The total number patients was 35, of whom 7 (20%) were women and 28 (80%) men, with a mean age 36.3 years (19.77). AETIOLOGY: 74% with post-traumatic arthritis, most of them secondary to gunshot wounds and fragmentation weapons, and neuropathic in 20%. An autogenous graft was used in 13 cases, and 14 cases using both, with a mean consolidation time of 4.37 months. Complications include, delayed union in 3 cases, and surgical site infection in 4. The postoperative functionality (AOFAS) mean was 66.7/100 points, with a score of 2.35 on a visual analogue pain scale. CONCLUSION: TTC arthrodesis using a humeral locking plate is a suitable option for fixing this type of arthrodesis, with a low rate of complications, and postoperative results that revealed satisfactory improvement in pain and consolidation. PMID- 26686280 TI - Spatially modulated structural colour in bird feathers. AB - Eurasian Jay (Garrulus glandarius) feathers display periodic variations in the reflected colour from white through light blue, dark blue and black. We find the structures responsible for the colour are continuous in their size and spatially controlled by the degree of spinodal phase separation in the corresponding region of the feather barb. Blue structures have a well-defined broadband ultra-violet (UV) to blue wavelength distribution; the corresponding nanostructure has characteristic spinodal morphology with a lengthscale of order 150 nm. White regions have a larger 200 nm nanostructure, consistent with a spinodal process that has coarsened further, yielding broader wavelength white reflectance. Our analysis shows that nanostructure in single bird feather barbs can be varied continuously by controlling the time the keratin network is allowed to phase separate before mobility in the system is arrested. Dynamic scaling analysis of the single barb scattering data implies that the phase separation arrest mechanism is rapid and also distinct from the spinodal phase separation mechanism i.e. it is not gelation or intermolecular re-association. Any growing lengthscale using this spinodal phase separation approach must first traverse the UV and blue wavelength regions, growing the structure by coarsening, resulting in a broad distribution of domain sizes. PMID- 26686281 TI - SMP-domain proteins at membrane contact sites: Structure and function. AB - SMP-domains are found in proteins that localize to membrane contact sites. Elucidation of the properties of these proteins gives clues as to the molecular bases underlying processes that occur at such sites. Described here are recent discoveries concerning the structure, function, and regulation of the Extended Synaptotagmin proteins and ERMES complex subunits, SMP-domain proteins at endoplasmic reticulum (ER)-plasma membrane and ER-mitochondrial contacts, respectively. They act as tethers contributing to the architecture of these sites and as lipid transporters that convey glycerolipids between apposed membranes. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26686282 TI - A Ve homologous gene from Gossypium barbadense, Gbvdr3, enhances the defense response against Verticillium dahliae. AB - The tomato Ve1 gene and several Ve1 homologues are involved in the resistance to Verticillium dahliae. Here, we report on another Ve homologous gene, Gbvdr3, from a Verticillium wilt-resistant cotton cultivar, Gossypium barbadense Hai7124, which has a 3207-bp region that encodes a predicted receptor-like protein. Transient expression analyses indicated that Gbvdr3 is localized in the plasma membrane, and virus-induced gene silencing of Gbvdr3 compromised the resistance of Hai7124 cotton to a defoliating strain of V. dahliae, V991, but not to a non defoliating strain, BP2. This resistance pattern was further confirmed by over expression of Gbvdr3 in transgenic Arabidopsis, which significantly elevated the expression of the ethylene-regulated gene GST2, the ethylene- and jasmonic acid regulated defense-related genes PR3 and PDF1.2, and the salicylic acid-regulated genes PR1 and PR5, but not the PR2 gene. It also triggered the accumulation of hydrogen peroxide and callose at early time points during infection by the V991 defoliating strain. In contrast, elevated accumulation of hydrogen peroxide or callose in Gbvdr3-expressed Arabidopsis leaves was not apparent under infection by the non-defoliating strain, BP2. These results suggested that Gbvdr3 is involved in the resistance to a unique spectrum of defoliating V. dahliae strains. PMID- 26686283 TI - CYP74B24 is the 13-hydroperoxide lyase involved in biosynthesis of green leaf volatiles in tea (Camellia sinensis). AB - Green leaf volatiles (GLVs) are C6-aliphatic aldehydes/alcohols/acetates, and biosynthesized from the central precursor fatty acid 13-hydroperoxides by 13 hydroperoxide lyases (HPLs) in various plant species. While GLVs have been implicated as defense compounds in plants, GLVs give characteristic grassy note to a bouquet of aroma in green tea, which is manufactured from young leaves of Camellia sinensis. Here we identify three HPL-related genes from C. sinensis via RNA-Sequencing (RNA-Seq) in silico, and functionally characterized a candidate gene, CYP74B24, as a gene encoding tea HPL. Recombinant CYP74B24 protein heterologously expressed in Escherichia coli specifically produced (Z)-3-hexenal from 13-HPOT with the optimal pH 6.0 in vitro. CYP74B24 gene was expressed throughout the aerial organs in a rather constitutive manner and further induced by mechanical wounding. Constitutive expression of CYP74B24 gene in intact tea leaves might account for low but substantial and constitutive formation of a subset of GLVs, some of which are stored as glycosides. Our results not only provide novel insights into the biological roles that GLVs play in tea plants, but also serve as basis for the improvement of aroma quality in tea manufacturing processes. PMID- 26686285 TI - Effects on the accumulation of calcium, magnesium, iron, manganese, copper and zinc of adding the two inorganic forms of selenium to solution cultures of Zea mays. AB - The addition of selenate or selenite to common fertilizers for crop production could be an effective way of producing selenium-rich food and feed. However, this would be feasible only if the increase in plant selenium (Se) content did not negatively influence the uptake of other essential elements. We therefore need to understand the interactions between Se and other major and trace elements during uptake by the plant. This study aimed to evaluate the influence of inorganic forms of Se on the accumulation of selected macronutrients (Ca and Mg) and micronutrients (Fe, Zn, Mn and Cu). Those essential elements are involved in the oxidative balance of cells. Zea mays seedlings were grown hydroponically in growth chambers in nutrient solutions to which we added 10, 50 or 1000 MUg.L(-1) of selenate and/or selenite. Cation accumulation was significantly affected by the addition of 50 MUg.L(-1) or 1000 MUg.L(-1) Se, but not by the presence of 10 MUg.L(-1) of Se in the nutrient solution. The highest concentration (1000 MUg.L( 1)) of Se in the nutrient solution affected the accumulation of essential cations in Zea mays: selenate tended to increase the accumulation of Mg, Zn and Mn, whereas a selenate/selenite mixture tended to decrease the accumulation of Ca, Mg, Zn and Mn. Only Fe accumulation was unaffected by Se whatever its form or concentration. Selenium may also affect the distribution of cations on Zea mays. For example, levels of Mg and Zn translocation to the shoots were lower in the presence of selenite. PMID- 26686284 TI - Arsenic toxicity in soybean seedlings and their attenuation mechanisms. AB - Even though vast areas contaminated with arsenic (As) are under soybean (Glycine max) cultivation, little is known about the growth and intrinsic antioxidant metabolism of soybean in response to As exposure. Thus, an evaluation was carried out of plant growth, root anatomy, antioxidant system and photosynthetic pigment content under arsenate (As(V)) and arsenite (As(III)) treatment. Soybean seedling growth was significantly affected at 25 MUM or higher concentrations of As(V) or As(III), and the toxic effect on root growth was associated with cell death of root tips. Microscopic analysis of cross-sections of As-treated root showed a reduction in the cortex area, dark deposits in cortex cells and broken cells in the outer layer. Similarly, in the vascular cylinder, dark deposits within xylem vessel elements and phloem cell walls were observed. In all the analyzed parameters, the deleterious effect was more evident under As(III) than As(V) treatment. Arsenic-treated soybean seedlings showed increased activity of antioxidant enzymes [total peroxidases (Px) and superoxide dismutase (SOD)] in root and shoot harvested after 2 and 5 d of treatment. However, a reduction in chlorophyll content and an increase in membrane lipids peroxidation were observed. It is suggested that root structural alterations induced by As, such as the particular pattern of dark depositions in the vascular system, could be associated with an adaptation or detoxification mechanism to prevent As translocation to the aboveground tissues. PMID- 26686286 TI - Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium. AB - We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and alpha-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18-19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of alpha-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate. PMID- 26686287 TI - Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model. AB - Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3beta-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti inflammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5 mg/kg, 25 mg/kg, and 50 mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25 mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment. PMID- 26686288 TI - Quinolinic acid-immunoreactivity in the naive mouse brain. AB - Quinolinic acid (QUIN) has been suggested to be involved in infections, inflammatory neurological disorders and in the development of psychiatric disorders. In this view, several studies have been performed to investigate QUIN localization in the brain and its neurotoxic effects. However, evidence is lacking regarding QUIN in healthy, control conditions. The aim of this study was to investigate the region-specific distribution and pattern of QUIN expression in the naive mouse brain. In addition, possible sex differences in QUIN immunoreactivity and its link with affect-related behavioural observations were assessed. For this purpose, naive mice were subjected to the forced swim test (FST) and 20 min open field (OF) testing to measure affect-related behaviour. Afterwards, brains were assessed for QUIN-immunoreactivity. QUIN-immunoreactivity was particularly observed in the cingulate cortex (CC), highlighting clearly delineated cells, and the thalamic reticular nucleus (TRN), showing a more diffuse staining pattern. Subsequently, QUIN-positive cells in the CC were counted, while QUIN-immunoreactivity in the TRN was examined using gray value measurements. No significant differences between sexes were observed for the number of QUIN-positive cells in the CC, neither in levels of QUIN immunoreactivity in the TRN. A direct correlation was found between QUIN-positive cells in the CC and QUIN-immunoreactivity in the TRN. Moreover, in male mice, a very strong correlation (rsp=.943; p<.01) between QUIN-immunoreactivity at the level of the TRN and motor activity in the OF was observed. Thus, our results suggest that QUIN - detected in the CC and the TRN - may play a role in regulating motor activity in normal conditions. PMID- 26686289 TI - Aging affects new cell production in the adult hippocampus: A quantitative anatomic review. AB - In the last century, cognitive impairment in elderly people was considered as the consequence of neuronal death. However, later analyses indicated that age-related reduction in neuron number was limited to specific regions of the central nervous system, and was irrelevant to brain dysfunction in both humans and non-human animals. Recent studies have indicated that progressive diminution of neural plasticity across an individual's life span may underlie age-related brain dysfunction. To date, various factors have been shown to contribute to neural plasticity. In particular, substantial data supports the importance of production of new cells in the adult brain: the rate of hippocampal neurogenesis wanes radically during aging; similarly, white matter homeostasis via oligodendrogenesis is also affected by aging. This review briefly summarizes quantitative studies on adult hippocampal neurogenesis and oligodendrogenesis. Although the hippocampus is traditionally recognized as the memory center of the brain, it has started to emerge as an integrator of cognition and emotion. One of the current research highlights is that diverse functions of the hippocampus are topographically embedded along its longitudinal and transverse axes. Here we discuss alterations in adult neurogenesis and oligodendrogenesis during aging from a topographic view point. The quantitative anatomic approach to age-related alterations in production of new cells in the hippocampus may give a novel insight into how brain functions suffer from aging. PMID- 26686290 TI - Melanin-concentrating hormone projections to the dorsal raphe nucleus: An immunofluorescence and in vivo microdialysis study. AB - Melanin-concentrating hormone (MCH)-containing neurons are localized in the lateral hypothalamus and incerto-hypothalamic areas, and project to several brain regions including the dorsal raphe nucleus (DRN). The MCHergic system has been involved in the regulation of emotional states and we have demonstrated that MCH microinjections into the rat DRN promote a depressive-like state. To understand the MCHergic transmission into the DRN, in the present study we characterized the distribution and density of the MCHergic fibers along the rostro-caudal axis of the rat DRN and their anatomical relationship with the 5-HT- and GABA-containing neurons. Additionally, a functional in vivo microdialysis study was carried out in order to evaluate the MCH effects on the 5-HT extracellular levels. Immunolabeling studies showed that MCHergic fibers were widely distributed throughout the rostro-caudal DRN extent and a reduced density at the most caudal level was observed. Interestingly, MCHergic fibers appeared in close apposition to 5-HT and GABA-containing neurons. Microdialysis studies evidenced an opposite effect of two concentrations of MCH on 5-HT levels: the lower concentration (30 MUM) produced a significant and long-lasting (up to 120 min) decrease while the higher (100 MUM) induced a slight and brief (20 min) increase. Morphological and functional results strongly suggest that both 5-HT- and GABA-containing neurons of the DRN are modulated by MCH. A different sensitivity of these neurons to MCH may explain the dose-response effect on 5-HT release. The decrease in extracellular 5-HT levels may account for the depressive-like effect induced by MCH reported in our previous studies. PMID- 26686291 TI - Three-dimensional visualization of the distribution of melanin-concentrating hormone producing neurons in the mouse hypothalamus. AB - We present here a new procedure to represent the 3D distribution of neuronal cell bodies within the brain, using exclusively softwares free for research purposes. Our technique is based on digitalized photos of brain slices processed by immunohistochemical technique, and the 3D Slicer software. The technique presented enables transposition of immunohistochemical or in situ hybridization data to the stereotaxic mouse brain atlas (e.g. Paxinos, G., Franklin, K.B.J., 2001. The Mouse Brain in Stereotaxic Coordinates. second ed. Academic Press, San Diego). By exporting the finalized models into a popular 3D design software (3DS Max) arbitrary environment and motion simulation can be created to improve the visual understanding of the area studied. Application of this technique provides the possibility to store, analyze and compare data - e.g. on the hypothalamic neuropeptides - across experimental techniques and laboratories. The method is exemplified by visualizing the distribution of immunohistochemically identified melanin-concetrating hormone (MCH) containing perikarya within the mouse hypothalamus. PMID- 26686292 TI - Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder. AB - Although major depressive disorder (MDD) and schizophrenia (SZ) are closely associated with disrupted functions in frontal and limbic areas of cerebral cortex, cellular pathology has also been found in other brain areas, including primary sensory cortex. Auditory cortex is of particular interest, given the prominence of auditory hallucinations in SZ, and sensory deficits in MDD. We used stereological sampling methods in auditory cortex to look for cellular differences between MDD, SZ and non-psychiatric subjects. Additionally, as all of our MDD subjects died of suicide, we evaluated the association of suicide with our measurements by selecting a SZ sample that was divided between suicide and non-suicide subjects. Measurements were done in primary auditory cortex (area A1) and auditory association cortex (area Tpt), two areas with distinct roles in sensory processing and obvious differences in neuron density and size. In MDD, densities of GABAergic interneurons immunolabeled for calretinin (CR) and calbindin (CB) were 23-29% lower than non-psychiatric controls in both areas. Parvalbumin (PV) interneurons (counted only in area Tpt) showed a nominally smaller (16%) reduction that was not statistically significant. Total neuron and glia densities measured in Nissl stained sections did not show corresponding reductions. Analysis of suicide in the SZ sample indicated that reduced CR cell density was associated with suicide, whereas the densities of CB and other cells were not. Our results are consistent with previous studies in MDD that found altered GABA-associated markers throughout the cerebral cortex including primary sensory areas. PMID- 26686294 TI - Differential developmental strategies by Sonic hedgehog in thalamus and hypothalamus. AB - The traditional concept of diencephalon (thalamus plus hypothalamus) and with it the entire traditional subdivision of the developing neural tube are being challenged by novel insights obtained by mapping the expression of key developmental genes. A model in which the hypothalamus is placed in the most rostral portion of the neural tube, followed caudally by a diencephalon formed by prethalamus, thalamus and pretectum has been proposed. The adult thalamus and hypothalamus are quite unlike each other in connectivity and functions. Here we review work on the role of the secreted morphogen protein Sonic hedgehog (Shh) in the developing diencephalon and hypothalamic region to show how different these two regions are also from this point of view. Shh from the prechordal plate (PCP) induces and patterns the hypothalamus but there is no evidence that this role is fulfilled by a morphogen gradient. Later, the hypothalamic primordium itself expresses Shh and a large part of the hypothalamus belongs to the Shh lineage, including the ventral domains. Neural Shh is necessary to complete the specification (lateral hypothalamus), differentiation and growth of the hypothalamus. Although Gli2A is the major effector of Shh in this region, hypothalamic specification also depends on the suppression of Gli3R by Shh secreted by the PCP as well as the neuroepithelium. The thalamus is patterned by an Shh morphogen gradient originated in the ZLI following similar mechanisms to those in the spinal cord. The thalamus itself does not belong to the Shh lineage. Gli2A is necessary for appropriate growth and specification of the thalamic nuclei, to the exception of the medial and intralaminar groups (limbic-related), whose development depends on Gli3R. Beyond specification and patterning, the scarce data available about cell sorting and aggregation in these two regions shows key differences between them as well. In summary, not only expression patterns but also developmental mechanisms support a separation of the traditional thalamus and hypothalamus into different prosomeric domains. PMID- 26686293 TI - Crosstalk among electrical activity, trophic factors and morphogenetic proteins in the regulation of neurotransmitter phenotype specification. AB - Morphogenetic proteins are responsible for patterning the embryonic nervous system by enabling cell proliferation that will populate all the neural structures and by specifying neural progenitors that imprint different identities in differentiating neurons. The adoption of specific neurotransmitter phenotypes is crucial for the progression of neuronal differentiation, enabling neurons to connect with each other and with target tissues. Preliminary neurotransmitter specification originates from morphogen-driven neural progenitor specification through the combinatorial expression of transcription factors according to morphogen concentration gradients, which progressively restrict the identity that born neurons adopt. However, neurotransmitter phenotype is not immutable, instead trophic factors released from target tissues and environmental stimuli change expression of neurotransmitter-synthesizing enzymes and specific vesicular transporters modifying neuronal neurotransmitter identity. Here we review studies identifying the mechanisms of catecholaminergic, GABAergic, glutamatergic, cholinergic and serotonergic early specification and of the plasticity of these neurotransmitter phenotypes during development and in the adult nervous system. The emergence of spontaneous electrical activity in developing neurons recruits morphogenetic proteins in the process of neurotransmitter phenotype plasticity, which ultimately equips the nervous system and the whole organism with adaptability for optimal performance in a changing environment. PMID- 26686295 TI - Different methods for evaluating the effects of microwave radiation exposure on the nervous system. AB - Microwave radiation (MWR) leads to hazardous effects on he central nervous system (CNS) for both human and animals. The widespread use of mobile phones has increased the risks of health problems in the CNS caused by radiofrequency (RF) electromagnetic fields. To determine these effects various methodological approaches related to neuroscience such as stereology, immunohistochemistry, and electron microscopy have been used. These approaches examine the effects on cells exposed to MWR at the light microscopic and ultrastructural levels, and novel information is obtained. The main aim of this paper is to discuss possible side effects of MWR in the light of current literature with different methodological approaches. PMID- 26686296 TI - Electromagnetic field and brain development. AB - Rapid advances in technology involve increased exposures to radio frequency/microwave radiation from mobile phones and other wireless transmitting devices. As cell phones are held close to the head during talking and often stored next to the reproductive organs, studies are mostly focused on the brain. In fact, more research is especially needed to investigate electromagnetic field (EMF)'s effects on the central nervous system (CNS). Several studies clearly demonstrate that EMF emitted by cell phones could affect a range of body systems and functions. Recent work has demonstrated that EMF inhibit the formation and differentiation of neural stem cells during embryonic development and also affect reproductive and neurological health of adults that have undergone prenatal exposure. The aim of this review is to discuss the developing CNS and explain potential impacts of EMF on this system. PMID- 26686297 TI - Spatial distribution of osteoblast activating peptide in the rat stomach. AB - Osteoblast activating peptide (OBAP) was previously reported to be expressed in the rat stomach and to have a vital role in osteogenesis, but its distribution in rat stomach has not been determined. Thus, the aim of the present study was to identify the cell types expressing OBAP in the rat stomach. The stomachs of twelve 10-to-11-week-old male Jc1:SD rats were used. Samples were collected for immunohistochemistry, immunoelectron microscopy and dot blot assay. Immunohistochemical investigation revealed that OBAP was distributed mainly in parietal cells without any expression in chief cells, X/A-like cells or enterochromaffin-like cells. Moreover, OBAP-immunopositive cells were observed mainly in the upper and lower parts of the gastric gland. Significantly high optical density of immunopositive cells was observed in the upper and lower gastric gland regions. The dot blot assay confirmed that OBAP is secreted by parietal cells and that it is present in the gastric gland lumen. Immunoelectron microscopy demonstrated that OBAP was confined to the mitochondrial inner membrane within parietal cells and that the number of mitochondria in the upper and lower parts of the gastric epithelium was significantly larger than the number in the middle part of the gastric epithelium. Based on the results, it was concluded that OBAP is mainly produced by mitochondria of parietal cells in the upper and lower parts of the gastric epithelium. Moreover, the presence of OBAP in the gastric gland lumen suggests an exocrine mechanism of release. PMID- 26686299 TI - Novel approach to measure drug release from nanomedicines. PMID- 26686298 TI - Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer. AB - Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (pPFS = 7.92 * 10(-6) and pOS = 5.27 * 10(-5)) and validation studies (pPFS = 3.66 * 10(-4) and pOS = 1.43 * 10(-4)). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients. PMID- 26686300 TI - Using Indigenist and Indigenous methodologies to connect to deeper understandings of Aboriginal and Torres Strait Islander peoples' quality of life. AB - The lack of a common description makes measuring the concept of quality of life (QoL) a challenge. Whether QoL incorporates broader social features or is attributed to health conditions, the diverse range of descriptions applied by various disciplines has resulted in a concept that is multidimensional and vague. The variety of theoretical conceptualisations of QoL confounds and confuses even the most astute. Measuring QoL in Aboriginal and Torres Strait Islander populations is even more challenging. Instruments commonly developed and used to measure QoL are often derived from research methodologies shaped by Western cultural perspectives. Often they are simply translated for use among culturally and linguistically diverse Aboriginal and Torres Strait Islander peoples. This has implications for Aboriginal and Torres Strait Islander populations whose perceptions of health are derived from within their specific cultures, value systems and ways of knowing and being. Interconnections and relationships between themselves, their communities, their environment and the natural and spiritual worlds are complex. The way in which their QoL is currently measured indicates that very little attention is given to the diversity of Aboriginal and Torres Strait Islander peoples' beliefs or the ways in which those beliefs shape or give structure and meaning to their health and their lives. The use of Indigenist or Indigenous methodologies in defining what Aboriginal and Torres Strait Islander peoples believe gives quality to their lives is imperative. These methodologies have the potential to increase the congruency between their perceptions of QoL and instruments to measure it. PMID- 26686302 TI - Comment on: Body composition changes in adolescents after laparoscopic sleeve gastrectomy. PMID- 26686301 TI - Non-Faradaic Electrochemical Detection of Exocytosis from Mast and Chromaffin Cells Using Floating-Gate MOS Transistors. AB - We present non-faradaic electrochemical recordings of exocytosis from populations of mast and chromaffin cells using chemoreceptive neuron MOS (CnuMOS) transistors. In comparison to previous cell-FET-biosensors, the CnuMOS features control (CG), sensing (SG) and floating gates (FG), allows the quiescent point to be independently controlled, is CMOS compatible and physically isolates the transistor channel from the electrolyte for stable long-term recordings. We measured exocytosis from RBL-2H3 mast cells sensitized by IgE (bound to high affinity surface receptors FcepsilonRI) and stimulated using the antigen DNP-BSA. Quasi-static I-V measurements reflected a slow shift in surface potential () which was dependent on extracellular calcium ([Ca]o) and buffer strength, which suggests sensitivity to protons released during exocytosis. Fluorescent imaging of dextran-labeled vesicle release showed evidence of a similar time course, while un-sensitized cells showed no response to stimulation. Transient recordings revealed fluctuations with a rapid rise and slow decay. Chromaffin cells stimulated with high KCl showed both slow shifts and extracellular action potentials exhibiting biphasic and inverted capacitive waveforms, indicative of varying ion-channel distributions across the cell-transistor junction. Our approach presents a facile method to simultaneously monitor exocytosis and ion channel activity with high temporal sensitivity without the need for redox chemistry. PMID- 26686303 TI - Esophageal abnormalities in morbidly obese adult patients. AB - BACKGROUND: An increase in body mass index has been found to be associated with an increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. Few systematic studies with objective tests have evaluated esophageal disorders in the morbidly obese population. OBJECTIVES: To define more precisely in morbidly obese people the incidence of esophageal symptoms and characterize the esophageal disorders using objective data. SETTING: University Hospital, Spain. METHODS: Two hundred twenty four presurgical morbidly obese patients were submitted to a protocol including a clinical history and objective tests (endoscopy, stationary esophageal manometry, 24-hour esophageal pH monitoring and isotopic emptying of the esophagus). RESULTS: In a morbidly obese population, heartburn (50.9%) and regurgitation (28.6%) were the most prevalent symptoms of GERD. Endoscopy registered hiatus hernia (12.5%) and reflux esophagitis (17.3%). Manometry was often abnormal (33.4%), with a hypotensive lower esophageal sphincter as the most common finding. Esophageal pH-metry was abnormal in 54.2% of the cases. Finally, 9.1% of the patients presented with abnormal isotopic esophageal emptying. A correlation between the degree of obesity and the severity of symptoms/objective tests for esophageal abnormalities could not be found. CONCLUSIONS: In morbidly obese patients, GERD is common, symptoms are unspecific, and there is a high prevalence of pH-metry and manometric abnormalities, unrelated to the degree of obesity. PMID- 26686304 TI - Comprehensive evaluation of the effect of bariatric surgery on pelvic floor disorders. AB - BACKGROUND: The association of pelvic floor disorders (PFD) with obesity is well documented. The spectrum of PFD includes stress urinary incontinence (SUI), urge urinary incontinence (UUI), pelvic organ prolapse (POP), and fecal incontinence (FI). Resolution or improvement of SUI after bariatric surgery has been previously reported. However, the data regarding UUI and other forms of PFD with objective testing are sparse. OBJECTIVES: Prospectively evaluate the effects of bariatric surgery on the prevalence and severity of pelvic floor disorders. SETTING: U.S. Academic Hospital. METHODS: From December 2008 to December 2012, patients who screened positive on a screening questionnaire were asked to participate in the study. Participants completed 3 validated condition-specific questionnaires before surgery and 6-12 months after. A subgroup consented to gynecologic examination (Pelvic Organ Prolapse Quantification [POP-Q] test) and urodynamic testing at similar time points. RESULTS: Seventy-two study patients underwent laparoscopic gastric bypass (n = 65), sleeve gastrectomy (n = 5), and gastric banding (n = 2). Mean BMI decreased from 47.5 to 32.7 kg/m(2) 1 year after surgery (P<.001). Based on questionnaires, the most prevalent PFD was SUI, identified in 60 (83.3%) patients at baseline and 32 (44.4%, P<.001) at follow up. There was significant improvement in PFD-related symptoms, quality of life, POP, and sexual function at follow-up. Decrease in prevalence of SUI after surgery was also confirmed with urodynamic testing (from 76.9% to 30.8%, P = .01). There was no significant change in prevalence and severity of POP based on POP-Q exam. CONCLUSIONS: Bariatric surgery is associated with a decrease in prevalence and severity of diverse forms of urinary incontinence as well as improvement in quality of life and sexual function of morbidly obese women. PMID- 26686305 TI - Normoglycemic ketoacidosis in a postoperative gastric bypass patient taking canagliflozin. PMID- 26686306 TI - Transection versus preservation of the neurovascular bundle of the lesser omentum in primary Roux-en-Y gastric bypass surgery. AB - BACKGROUND: A gastric pouch in Roux-en-Y gastric bypass (RYGB) surgery can be created after transection of the perigastric neurovascular bundle or by preserving these structures. Some surgeons choose to transect the neurovascular bundle (NBT), containing branches of the vagus nerve, because this might be related to additional weight loss, whereas others advocate preservation (NBP) to reduce postoperative complications. OBJECTIVES: This study assessed the effect of both techniques after primary RYGB. SETTING: All patients undergoing primary RYGB in a large bariatric center in the Netherlands between January 2010 and December 2013 were included. METHODS: Patient demographic characteristics, operative details, postoperative complications and weight loss after 1 year were retrospectively analyzed. RESULTS: A total of 773 consecutive patients were included (85.5% female). NBT was performed in 407 patients (52.7%), whereas NBP was performed in 366 patients. There were no missing data and 81.2% of patients completed the 1-year follow-up. Postoperative complications were found in 66 patients (8.5%). A total of 49 patients (6.3%) either had an anastomotic leakage, postoperative bleeding, or intraabdominal abscess (NBT 8.8% versus NBP 3.6%, P = .003). Percentage total weight loss (NBT 34.5%+/-6.9% versus NBP 33.4%+/-6.9%; P = .011) differed to a lesser extent between groups, although this was significant. Neurovascular bundle transection was identified as independent factor among others for occurrence of leakage, bleeding, and abscess development (OR 2.886; 95% CI [1.466-5.683]; P = .002). CONCLUSIONS: Transection of the neurovascular bundle in RYGB is associated with more complications. Furthermore, weight loss is not relevantly increased. Further research is necessitated to substantiate these findings. PMID- 26686307 TI - Metabolic surgery provides remission of pancreatogenic diabetes in a non-obese patient. PMID- 26686308 TI - Bariatric outcomes and the three-legged stool. PMID- 26686309 TI - Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study. AB - BACKGROUND: The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking. OBJECTIVES: The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs). SETTING: University hospital. METHODS: A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2*4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA. RESULTS: A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution. CONCLUSIONS: This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs. (Surg Obes Relat Dis 2015;0:000-000.) (c) 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved. PMID- 26686310 TI - Comment on: Laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass lead to equal changes in body composition and energy metabolism 17 months postoperatively: a prospective randomized trial. PMID- 26686311 TI - Laparoscopic revision of chronic marginal ulcer and bilateral truncal vagotomy. PMID- 26686312 TI - Endocrine treatment for ductal carcinoma in situ: balancing risks and benefits. PMID- 26686314 TI - Metabolic engineering of long chain-polyunsaturated fatty acid biosynthetic pathway in oleaginous fungus for dihomo-gamma linolenic acid production. AB - Microbial lipids are promising alternative sources of long chain-polyunsaturated fatty acids (LC-PUFAs) for food, feed, nutraceutical and pharmaceutical sectors. Dihomo-gamma-linolenic acid (C20:3Delta(8,11,14); DGLA) is an important LC-PUFAs with anti-inflammatory and anti-proliferative effects. To generate a DGLA producing strain, fatty acid reconstitution in Aspergillus oryzae was performed by metabolic engineering through co-expression of codon-optimized Pythium Delta(6)-desaturase and Delta(6)-elongase, which had high conversion rates of substrates to respective products as compared to the native enzymes. The Delta(6) desaturated and Delta(6)-elongated products, gamma-linolenic acid (C18:3Delta(6,9,12); GLA) and DGLA, were accumulated in phospholipids rather than triacylglycerol. Interestingly, the manipulation of lipid quality in the oleaginous fungus did not affect growth and lipid phenotypes. This strategy might expand to development of the oleaginous fungal strain for producing other tailor made oils with industrial applications. PMID- 26686315 TI - Overexpression of YY1 increases the protein production in mammalian cells. AB - The production of therapeutic antibodies using mammalian cells remains a high priority in the biopharmaceutical manufacturing industry. Bioengineers have targeted different cellular processes, including transcription, translation, secretion and post-translational modifications, to overcome the metabolic bottlenecks limiting production capacity and create high-producing mammalian cell lines. The polycomb group (PcG) proteins belong to a family of chromatin regulators with important roles in multicellular development. By overexpressing and screening genes from the PcG family, we have identified an epigenetic key player for biopharmaceutical manufacturing enhancement: the transcription factor Yin Yang 1 (YY1). The overexpression of YY1 led to an increase in the production of several product genes (SEAP, VEGF165, IgG including Rituximab), provided that human YY1 (hYY1) was expressed in human cells (HeLa, HT-1080, HEK-293T, FreeStyleTM 293-F) and Chinese hamster ovary cell-derived YY1 (cYY1) was expressed in CHO cells (CHO-K1, CHO-easyC, FreeStyleTM CHO-S, CHO-B13-24, CHO IgG1). Ectopic expression of cYY1 in the stable CHO-derived IgG producer cell lines CHO-B13-24 and CHO-IgG1 increased the antibody titer up to 6-fold, suggesting that epigenetic engineering of mammalian production cell lines could become a new strategy to improve the manufacturing of complex protein pharmaceuticals. PMID- 26686316 TI - No evidence for an effect of traffic noise on the development of the corticosterone stress response in an urban exploiter. AB - Anthropogenic noise can have important physiological and behavioral effects on wild animals. For example, urban noise could lead to a state of chronic stress and could alter the development of the hypothalamus-pituitary-adrenal (HPA) axis. Supporting this hypothesis, several studies have found that human disturbance is associated with increased circulating corticosterone (CORT) levels. However, it remains unclear whether increased CORT levels are the result of anthropogenic noise or other anthropogenic factors. Here, we experimentally tested the impact of urban noise on the CORT stress response in an urban exploiter (the house sparrow, Passer domesticus) by exposing chicks to a traffic noise ('disturbed chicks') or not ('control chicks'). If noise exposure has a negative impact on developing chicks, we predicted that (1) disturbed chicks will grow slower, will be in poorer condition, and will have a lower fledging probability than controls; (2) disturbed chicks will have higher baseline CORT levels than control; (3) the CORT stress response will be affected by this noise exposure. Contrary to these predictions, we found no effect of our experiment on growth, body condition, and fledging success, suggesting that house sparrow chicks were not negatively affected by this noise exposure. Moreover, we did not find any effect of noise exposure on either baseline CORT levels or the CORT stress response of chicks. This suggests not only that house sparrow chicks did not perceive this noise as stressful, but also that the development of the HPA axis was not affected by such noise exposure. Our study suggests that, contrary to urban avoiders, urban exploiters might be relatively insensitive to urban noise during their development. Further comparative studies are now needed to understand whether such insensitivity to anthropogenic noise is a consistent phenomenon in urban exploiters and whether this is a major requirement of an urban way of life. PMID- 26686317 TI - Evaluation of physiological stress in Australian wildlife: Embracing pioneering and current knowledge as a guide to future research directions. AB - Australia has a rich terrestrial and marine biodiversity and high species endemism. However, the oceanic continent is facing the biodiversity extinction crisis. The primary factors are anthropogenic induced environmental changes, including wildlife habitat destruction through urbanisation and predation by feral animals (e.g. red foxes and feral cats), increased severity of diseases (e.g. chytridiomycosis and chlamydia), and increased occurrence of summer heat waves and bush fires. Stress physiology is a dynamic field of science based on the studies of endocrine system functioning in animals. The primary stress regulator is the hypothalamo-pituitary adrenal (interrenal) axis and glucocorticoids (corticosterone and/or cortisol) provide stress index across vertebrate groups. This review paper focuses on physiological stress assessments in Australian wildlife using examples of amphibians, reptiles, birds and marsupials. I provide a thorough discussion of pioneering studies that have shaped the field of stress physiology in Australian wildlife species. The main findings point towards key aspects of stress endocrinology research, such as quantification of biologically active levels of glucocorticoids, development of species-specific GC assays and applications of stress physiology approaches in field ecology and wildlife conservation programs. Furthermore, I also discuss the importance of chronic stress assessment in wildlife populations. Finally, I provide a conceptual framework presenting key research questions in areas of wildlife stress physiology research. In conclusion, wildlife management programs can immensely benefit from stress physiology assessments to gauge the impact of human interventions on wildlife such as species translocation and feral species eradication. PMID- 26686318 TI - Early-life stress changes expression of GnRH and kisspeptin genes and DNA methylation of GnRH3 promoter in the adult zebrafish brain. AB - Early-life stress can cause long-term effects in the adulthood such as alterations in behaviour, brain functions and reproduction. DNA methylation is a mechanism of epigenetic change caused by early-life stress. Dexamethasone (DEX) was administered to zebrafish larvae to study its effect on reproductive dysfunction. The level of GnRH2, GnRH3, Kiss1 and Kiss2 mRNAs were measured between different doses of DEX treatment groups in adult zebrafish. Kiss1 and GnRH2 expression were increased in the 200mg/L DEX treated while Kiss2 and GnRH3 mRNA levels were up-regulated in the 2mg/L DEX-treated zebrafish. The up regulation may be related to programming effect of DEX in the zebrafish larvae, causing overcompensation mechanism to increase the mRNA levels. Furthermore, DEX treatment caused negative impact on the development and maturation of the testes, in particular spermatogenesis. Therefore, immature gonadal development may cause positive feedback by increasing GnRH and Kiss. This indicates that DEX can alter the regulation of GnRH2, GnRH3, Kiss1 and Kiss2 in adult zebrafish, which affects maturation of gonads. Computer analysis of 1.5 kb region upstream of the 5' UTR of Kiss1, Kiss2, GnRH2 and GnRH3 promoter showed that there are putative binding sites of glucocorticoid response element and transcription factors involved in stress response. GnRH3 promoter analysed from pre-optic area, ventral telencephalon and ventral olfactory bulb showed higher methylation at CpG residues located on -1410, -1377 and -1355 between control and 2mg/L DEX-treated groups. Hence, early-life DEX treatment can alter methylation of GnRH3 gene promoter, which subsequently affects gene regulation and reproductive functions. PMID- 26686319 TI - In vitro and in silico studies on cell adhesion protein peroxinectin from Fenneropenaeus indicus and screening of heme blockers against activity. AB - In invertebrates, the prophenoloxidase (proPO) pathway is involved in the phenol like antioxidant production against invading pathogens. Overproduction of melanin and phenolic substances leads to the disruption of hemocytes (own host cells); therefore, there is a prerequisite to regulate the antioxidant production, which is performed by the proteases and proPO-associated cell adhesion protein peroxinectin (PX). PX is a macromolecular structure consisting of protein involved in the proPO pathway, which is a potential target in the regulatory mechanism in crustaceans. In the proPO cascade, pattern recognition proteins initiate the proPO cascade by the consequent reaction, and PX is involved in the key step in the regulatory mechanism of phenoloxidase enzyme synthesis. In the present study, Indian white shrimp Fenneropenaeus indicus PX (Fein-PX) gene sequence was used. Upregulation of Fein-PX was determined using immunostimulants beta-glucan (agonists) and examined its expression by quantitative RT-PCR. To find the downregulation or negative regulation of Fein-PX, inhibitors were screened, and its 3D model provides molecular insights into the rationale inhibitor design for developing an effective molecule against Fein-PX. PMID- 26686320 TI - Purpura fulminans associated with acute West Nile virus encephalitis. AB - Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection. PMID- 26686321 TI - Outstanding bioinorganic contributions from the International Symposium on Metal Complexes, Pavia, Italy, 2014 (ISMEC2014). PMID- 26686322 TI - Chemoprevention of colorectal neoplasia. AB - BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups. PMID- 26686323 TI - Novel X-linked syndrome of cardiac valvulopathy, keloid scarring, and reduced joint mobility due to filamin A substitution G1576R. AB - Filamin A (FLNA) is known to be involved in intracellular actin binding, cell migration, scaffolding, and signaling. We report a novel X-linked syndrome characterized by cardiac valvular disease, keloid scarring and reduced joint mobility in male second cousins due to a previously unreported mutation in FLNA. Whole exome sequencing was performed using standard methods and segregation analysis was performed in affected and non-affected family members. A novel hemizygous c.4726G>A (p.G1576R) mutation in FLNA was detected. Segregation analysis performed on multiple maternal family members showed c.4726G>A (p.G1576R) segregated with disease in an X-linked inheritance pattern. The findings in these cases are distinct from previously described FLNA related disorders by virtue of decreased joint mobility and spontaneous keloid scarring. They occur in association with a novel mutation and represent a novel genetic syndrome. PMID- 26686324 TI - Capabilities and the Definition of Health: Comments on Venkatapuram. AB - Sridhar Venkatapuram's Health Justice argues that health is a 'metacapability' - specifically, as the metacapability of having the ten 'central human capabilities' described by Martha Nussbaum. This cannot be right, as it provides no basis for distinguishing health from education, riches, or love. An amendment correcting this problem is suggested, namely that health is the involuntary, bodily aspect of the metacapability for the central capabilities. This amendment is defended against the objection that it fails to capture some important aspects of mental health. PMID- 26686325 TI - Sridhar Venkatapuram's Health Justice: A Collection of Critical Essays and A Response from the Author. PMID- 26686326 TI - Venkatapuram's Capability theory of Health: A Critical Discussion. AB - The discussion about theories of health has recently had an important new input through the work of Sridhar Venkatapuram. He proposes a combination of Lennart Nordenfelt's holistic theory of health and Martha Nussbaum's version of the capability approach. The aim of the present article is to discuss and evaluate this proposal. The article starts with a discussion of Nordenfelt's theory and evaluates Venkatapuram' critique of it, that is, of its relativism, both regarding goals and environment, and of the subjectivist theory of happiness used. Then the article explains why Nordenfelt's idea of a reasonable environment is not a problem for the theory, and it critiques Venkatapuram's own incorporation of the environment into the concept of health, suggesting that this makes the concept too wide. It contends, moreover, that Venkatapuram's alternative theory retains a problem inherent in Nordenfelt's theory, namely, that health is conceived of as a second-order ability. It is argued that health should, instead, be defined as first-order abilities. This means that health cannot be seen as a capability, and also that health cannot be seen as a meta capability of the kind envisioned by Venkatapuram. It is, furthermore, argued that the theory lacks one crucial aspect of health, namely, subjective wellbeing. Finally, the article tries to illustrate how health, in the suggested alternative sense, as first-order abilities, fits into Nussbaum's capability theory, since health as an 'actuality' is part of all the 'combined capabilities' suggested by Nussbaum. PMID- 26686313 TI - Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. AB - BACKGROUND: Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. METHODS: In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. RESULTS: Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7.2 years (IQR 5.6 8.9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0.89 [95% CI 0.64-1.23]). The non-inferiority of anastrozole was established (upper 95% CI <1.25), but its superiority to tamoxifen was not (p=0.49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0.93 [95% CI 0.58-1.50], p=0.78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. CONCLUSIONS: No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences. FUNDING: Cancer Research UK, National Health and Medical Research Council Australia, Breast Cancer Research Fund, AstraZeneca, Sanofi Aventis. PMID- 26686327 TI - The Metric and the Threshold Problem for Theories of Health Justice: A Comment on Venkatapuram. AB - Any theory of health justice requires an account of what areas of social life are important enough to be of public concern. What are the goods that ought to be provided as a matter of justice? This is what I will call the metric problem. The capabilities approach puts forward a particular solution to this problem. In this article I will discuss some issues of such an approach in relation to Sridhar Venkatapuram's well-known theory. Another problem I examine is how to determine a threshold of provision within a theory of justice. What is enough in terms of health justice? I argue that we need such a threshold to avoid healthism, the expansion of the pursuit of health over and above the treatment and prevention of disease. This is an especially pertinent problem in public health, which is also the context of Venkatapuram's theory. PMID- 26686328 TI - Capabilities and Incapabilities of the Capabilities Approach to Health Justice. AB - This first part of this article critiques Sridhar Venkatapuram's conception of health as a capability. It argues that Venkatapuram relies on the problematic concept of dignity, implies that those who are unhealthy lack lives worthy of dignity (which seems politically incorrect), sets a low bar for health, appeals to metaphysically problematic thresholds, fails to draw clear connections between appealed-to capabilities and health, and downplays the importance/relevance of health functioning. It concludes by questioning whether justice entitlements should pertain to the capability for health versus health achievements, challenging Venkatapuram's claims about the strength of health entitlements, and demonstrating that the capabilities approach is unnecessary to address social determinants of health. PMID- 26686329 TI - Vulnerability, Health Agency and Capability to Health. AB - One of the defining features of the capability approach (CA) to health, as developed in Venkatapuram's book Health Justice, is its aim to enable individual health agency. Furthermore, the CA to health hopes to provide a strong guideline for assessing the health-enabling content of social and political conditions. In this article, I employ the recent literature on the liberal concept of vulnerability to assess the CA. I distinguish two kinds of vulnerability. Considering circumstantial vulnerability, I argue that liberal accounts of vulnerability concerned with individual autonomy, align with the CA to health. Individuals should, as far as possible, be able to make health-enabling decisions about their lives, and their capability to do so should certainly not be hindered by public policy. The CA to health and a vulnerability-based analysis then work alongside to define moral responsibilities and designate those who hold them. Both approaches demand social policy to address circumstances that hinder individuals from taking health-enabling decisions. A background condition of vulnerability, on the other hand, even though it hampers the capability for health, does not warrant the strong moral claim proposed by the CA to health to define health as a meta-capability that should guide social policy. Nothing in our designing social policy could change the challenge to health agency when we deal with background conditions of vulnerability. PMID- 26686330 TI - Humanity and Justice in Global Health: Problems with Venkatapuram's Justification of the Global Health Duty. AB - One of the most ambitious and sophisticated recent approaches to provide a theory of global health justice is Sridhar Venkatapuram's recent work. In this commentary, we first outline the core idea of Venkatapuram's approach to global health justice. We then argue that one of the most important elements of the account, Venkatapuram's basis of global health duties, is either too weak or assumed implicitly without a robust justification. The more explicit grounding of the duty to protect and promote health capabilities is based on Martha Nussbaum's version of the capability approach. We argue that this foundation gives rise to humanitarian duties rather than duties of justice proper. Venkatapuram's second argument from the social determinants of health thesis is instead a stronger candidate for grounding duties of justice. However, as a justificatory argument, it is only alluded to and has not yet been spelled out sufficiently. We offer plausible justificatory steps to fill this gap and draw some implications for global health action. We believe this both strengthens Venkatapuram's approach and serves to broaden the basis for future action in the area of global health. PMID- 26686331 TI - On Health Justice. Some Thoughts and Responses to Critics. PMID- 26686332 TI - Children and Clinical Research: A Response to Chwang. PMID- 26686333 TI - Flexible link functions in nonparametric binary regression with Gaussian process priors. AB - In many scientific fields, it is a common practice to collect a sequence of 0-1 binary responses from a subject across time, space, or a collection of covariates. Researchers are interested in finding out how the expected binary outcome is related to covariates, and aim at better prediction in the future 0-1 outcomes. Gaussian processes have been widely used to model nonlinear systems; in particular to model the latent structure in a binary regression model allowing nonlinear functional relationship between covariates and the expectation of binary outcomes. A critical issue in modeling binary response data is the appropriate choice of link functions. Commonly adopted link functions such as probit or logit links have fixed skewness and lack the flexibility to allow the data to determine the degree of the skewness. To address this limitation, we propose a flexible binary regression model which combines a generalized extreme value link function with a Gaussian process prior on the latent structure. Bayesian computation is employed in model estimation. Posterior consistency of the resulting posterior distribution is demonstrated. The flexibility and gains of the proposed model are illustrated through detailed simulation studies and two real data examples. Empirical results show that the proposed model outperforms a set of alternative models, which only have either a Gaussian process prior on the latent regression function or a Dirichlet prior on the link function. PMID- 26686334 TI - Imaging with (124)I in differentiated thyroid carcinoma: is PET/MRI superior to PET/CT? AB - PURPOSE: The aim of this study was to compare integrated PET/CT and PET/MRI for their usefulness in detecting and categorizing cervical iodine-positive lesions in patients with differentiated thyroid cancer using (124)I as tracer. METHODS: The study group comprised 65 patients at high risk of iodine-positive metastasis who underwent PET/CT (low-dose CT scan, PET acquisition time 2 min; PET/CT2) followed by PET/MRI of the neck 24 h after (124)I administration. PET images from both modalities were analysed for the numbers of tracer-positive lesions. Two different acquisition times were used for the comparisons, one matching the PET/CT2 acquisition time (2 min, PET/MRI2) and the other covering the whole MRI scan time (30 min, PET/MRI30). Iodine-positive lesions were categorized as metastasis, thyroid remnant or inconclusive according to their location on the PET/CT images. Morphological information provided by MRI was considered for evaluation of lesions on PET/MRI and for volume information. RESULTS: PET/MRI2 detected significantly more iodine-positive metastases and thyroid remnants than PET/CT2 (72 vs. 60, p = 0.002, and 100 vs. 80, p = 0.001, respectively), but the numbers of patients with at least one tumour lesion identified were not significantly different (21/65 vs. 17/65 patients). PET/MRI30 tended to detect more PET-positive metastases than PET/MRI2 (88 vs. 72), but the difference was not significant (p = 0.07). Of 21 lesions classified as inconclusive on PET/CT, 5 were assigned to metastasis or thyroid remnant when evaluated by PET/MRI. Volume information was available in 34 % of iodine-positive metastases and 2 % of thyroid remnants on PET/MRI. CONCLUSIONS: PET/MRI of the neck was found to be superior to PET/CT in detecting iodine-positive lesions. This was attributed to the higher sensitivity of the PET component, Although helpful in some cases, we found no substantial advantage of PET/MRI over PET/CT in categorizing iodine positive lesions as either metastasis or thyroid remnant. Volume information provided by MRI for some iodine-positive lesions might be useful in dosimetry. PMID- 26686335 TI - Occupational radiation exposure of medical staff performing 90Y-loaded microsphere radioembolization. AB - PURPOSE: Radioembolization of liver cancer with (90)Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting (90)Y-loaded glass and resin microspheres especially in view of the increasing use of these products. METHODS: Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. RESULTS: Chest exposure was very low for both products used (<10 MUSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 +/- 5.2 MUSv/GBq for the radiopharmacist, and initially 17.9 +/- 5.4 MUSv/GBq for the nuclear medicine physician reducing to 13.97 +/- 7.9 MUSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 +/- 271.9 MUSv/GBq but with a reduction with increasing experience to 97.5 +/- 35.2 MUSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 +/- 156 MUSv/GBq. CONCLUSION: Medical staff performing (90)Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using (131)I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolization. PMID- 26686337 TI - Enhanced Thermostability of Lipoxygenase from Anabaena sp. PCC 7120 by Site Directed Mutagenesis Based on Computer-Aided Rational Design. AB - Lipoxygenase from Anabaena sp. PCC 7120 (Ana-LOX) was thermally unstable. So, improving the thermostability of the enzyme was quite essential. The target site of Ana-LOX selected for site-directed mutagenesis was based on computer-aided rational design. The thermostability and specific activity of Ana-LOX were improved with replacing valine with alanine at the target site 421 and the site 40. Compared to the wild-type enzyme which has a half-life (T 1/2) of inactivation of 3.8 min at 50 degrees C, the T 1/2 of mutant enzymes with V421A and V40A substitution increased to 4.4 and 7.0 min, respectively. The double mutant V421A/V40A showed a synergistic effect with a T 1/2 value of 8.3 min, resulting in a 1.18-fold improvement compared to the original Ana-LOX. V421A, V40A, and V421A/V40A also obtained 4.83, 41.58, and 80.07 % increase in specific activity, respectively. This study provides useful theoretical reference for enzyme molecular modification and computer-aided rational design. PMID- 26686338 TI - In Vitro Release Kinetics and Transferrin Saturation Study of Intravenous Iron Sucrose Entrapped in Poly(ethylene glycol)-Assisted Silica Xerogel. AB - The presence of labile iron fractions in intravenous iron supplements compromises their safety. Poly(ethylene glycol) (PEG)-assisted silica xerogel was evaluated as a potential drug carrier for iron sucrose with the purpose of limiting labile iron available for in vitro uptake by transferrin. The drug entrapped xerogels were synthesized by the sol-gel process with varying amounts of PEG. In vitro release studies were conducted in simulated body fluid (SBF) at 37 +/- 0.02 degrees C (pH 7.4). The results indicated that the cumulative release percentage increased with the increase in the amount of PEG in the matrix. The biphasic release profile followed first-order kinetics for the first 6 h and Higuchi model for the remaining time (up to 168 h). The sample showing highest percentage of cumulative release (the xerogel with 16 % PEG) was used for in vitro transferrin saturation studies in contrast with the plain drug. The xerogel formulation exhibited 7.25 +/- 0.4 % transferrin saturation in 180 min as compared to 12.89 +/- 0.2 % for the raw drug. These results indicate that encapsulation of iron sucrose in PEG-assisted silica xerogel and subsequent sustained release from the matrix can improve the safety of the drug when presence of labile iron is a major concern. PMID- 26686339 TI - The Impact of Red Blood Cell Distribution Width and Neutrophil/Lymphocyte Ratio on the Diagnosis of Major Depressive Disorder. AB - INTRODUCTION: Major depressive disorder (MDD) is an important risk factor for cardiovascular mortality and morbidity. Red blood cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) can be obtained with a basic hemogram test. These parameters have been found as a predictor of mortality in the general population and in several diseases such as cardiovascular disease. METHODS: Our study included 100 patients with newly diagnosed MDD and 100 healthy control patients (who had no depressive symptoms and without heart disease) admitted to our outpatient clinics. Patients with MDD were started on selective serotonin reuptake inhibitor (SSRI) treatment and followed up for 3 months. Both MDD and control patients' laboratory tests and physical, neurological, and psychiatric examinations were performed both at diagnosis and after 3 months of treatment. RESULTS: In total, 100 patients with MDD were evaluated and 80 were included in our study. The control group consisted of 91 healthy individuals. The mean age was 44 +/- 10.6 years for patients with MDD and 39.8 +/- 11.4 years for the control group. There was no significant difference between the age for groups (P = 0.13); 55% of patients with MDD and 33% of the control group was male. NLR levels were found to be 2.55 +/- 0.7 and RDW levels were found to be 14.3 +/- 2.6 in patients with MDD; NLR levels were found to be 1.41 +/- 0.8 and RDW levels were found to be 13.4 +/- 1.8 in the control group. RDW and NLR levels were significantly higher in patients with MDD compared to the control group. The significant difference between the levels of RDW and NLR in patients with MDD and the control group was dissolved after SSRI treatment (P < 0.001). RDW [median 14.3, interquartile range (IQR) 2.8 vs. median 13.25, IQR 2.45; P < 0.001] and NLR (median 2.3, IQR 1.1 vs. median 2.0, IQR 1.15; P < 0.001) levels were significantly higher in patients with MDD compared to the control group. CONCLUSION: Our study showed that hematological inflammatory markers might be useful parameters that can be used in patients with MDD for coronary artery disease risk. Specifically, RDW and NLR seem to be more hopeful. Advanced, detailed, and larger studies are needed. PMID- 26686340 TI - The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors. AB - NAB2-STAT6 gene fusion drives STAT6 nuclear expression and is the pathognomonic hallmark of solitary fibrous tumors (SFTs). However, no study has systematically analyzed the clinicopathological features, STAT6 immunoexpression status, or the fusion variants of NAB2-STAT6 in intrathoracic SFTs. Fifty-two intrathoracic SFTs were retrieved to appraise histopathology, assess STAT6 immunoexpression, and determine NAB2-STAT6 fusion variants by RT-PCR. Location-relevant histologic mimics served as controls. Thirty-one pleura-based, 12 mediastinal/pericardial, and nine intrapulmonary lesions were histologically categorized into eight malignant, eight atypical, and 36 conventional or cellular SFTs, including two fat-forming and two giant cell angiofibroma-like SFTs. STAT6 distinctively decorated the tumoral nuclei in 51 (98%) SFTs. However, no nuclear staining was observed in the histological mimics. NAB2-STAT6 fusion was detected in 34 SFTs. Twenty-nine (85.3%) exhibited the major NAB2ex4-STAT6ex2/3 variant and 5 (14.7%) the minor NAB2ex6-STAT6ex16/17. NAB2ex4-STAT6ex2 was significantly associated with older age (P = 0.01) and pleuropulmonary tumors (P = 0.025). After a median follow-up of 33.9 (range, 0.3-174.6) months, adverse outcomes occurred in one atypical and five malignant SFTs, including two local relapses, one intrapulmonary metastasis, and three extrathoracic metastases. Inferior disease free survival was univariately associated with atypical/malignant histology (P = 0.001) and a mitosis >4/10 HPFs (P = 0.0012) but was unrelated to fusion variants. In conclusion, the majority of intrathoracic SFTs exhibited STAT6 nuclear staining, and NAB2ex4-STAT6ex2/3 was the predominant fusion type. However, clinical aggressiveness is associated with atypical/malignant histology primarily contributed by increased mitosis but was unrelated to the NAB2-STAT6 fusion variants. PMID- 26686341 TI - The anti-adhesive and anti-aggregatory effects of phenolics from Trifolium species in vitro. AB - The present in vitro study includes a comparative evaluation of anti-platelet (anti-thrombotic) properties of plant phenolics, isolated from nine different clover (Trifolium) species. The analysis covered phenolic fractions isolated from T. alexandrinum L., T. fragiferum L., T. hybridum L., T. incarnatum L., T. pallidum Waldst et Kit., T. resupinatum L. var. majus Boiss, T. resupinatum L. var. resupinatum, T. scabrum L., and T. pratense L. (red clover). The inhibitory effects of plant preparations (1-50 ug/ml) on hemostatic functions of blood platelets were assessed by measurements of thrombin- or ADP-induced platelet adhesion to fibrinogen, platelet aggregation in platelet-rich plasma (activated with ADP or collagen), and by the determination of PF-4 secretion from platelet alpha-granules. The influence of T. phenolics on arachidonic cascade in blood platelets was also determined. T. resupinatum var. majus, T. resupinatum var. resupinatum, and T. scabrum had the strongest anti-platelet effects. These preparations displayed the most evident anti-adhesive and anti-aggregatory effects in response to all of the used agonists: thrombin (0.2 U/ml), ADP (10 uM), and collagen (2 ug/ml), and their inhibitory properties were also confirmed by an analysis of PF-4 secretion. T. scabrum and some of other examined clover species possess significantly higher concentrations of both isoflavones and other bioactive phenolics, when compared to red clover. The obtained results suggest that these clovers contain substances with potent anti-platelet properties. PMID- 26686342 TI - Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker. AB - BACKGROUND: Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha synuclein also has been reported in healthy individuals. OBJECTIVES: We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD. METHODS: We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity. RESULTS: No difference was seen in the enteric alpha-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P < 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD. CONCLUSIONS: The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains. PMID- 26686343 TI - Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis. AB - BACKGROUND/PURPOSE: Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years. METHODS: Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1 10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated. RESULTS: While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS. CONCLUSION: While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted. PMID- 26686336 TI - Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries. AB - PURPOSE: Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. METHODS: In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest of-the-world (RoW). RESULTS: Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 +/- 3.4 mSv (RoW 11.4 +/- 4.3 mSv; P < 0.001) and of PET was 2.6 +/- 1.5 mSv (RoW 3.8 +/- 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 +/- 1.2, which was higher than the RoW score (5.0 +/- 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. CONCLUSION: In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice. PMID- 26686344 TI - Interference in the tundra predator guild studied using local ecological knowledge. AB - The decline or recolonization of apex predators such as wolves and lynx, often driven by management decisions, and the expansion of smaller generalist predators such as red foxes, can have important ecosystem impacts. The mesopredator release hypothesis proposes that apex predators control medium-sized predator populations through competition and/or intraguild predation. The decline of apex predators thus leads to an increase in mesopredators, possibly with a negative impact on prey populations. Information about the abundance of mammalian tundra predators, wolf (Canis lupus), wolverine (Gulo gulo), lynx (Lynx lynx), red fox (Vulpes vulpes) and arctic fox (Vulpes lagopus) was collected from local active outdoors people during semi-structured interviews in 14 low arctic or sub-arctic settlements in western Eurasia. The perceived abundance of red fox decreased with higher wolf abundance and in more arctic areas, but the negative effect of wolves decreased in more arctic and therefore less productive ecosystems. The perceived abundance of arctic fox increased towards the arctic and in areas with colder winters. Although there was a negative correlation between the two fox species, red fox was not included in the model for perceived arctic fox abundance, which received most support. Our results support the mesopredator release hypothesis regarding the expansion of red foxes in subarctic areas and indicate that top down control by apex predators is weaker in less productive and more arctic ecosystems. We showed that local ecological knowledge is a valuable source of information about large-scale processes, which are difficult to study through direct biological investigations. PMID- 26686358 TI - Study on the catalytic performance of laccase in the hydrophobic ionic liquid based bicontinuous microemulsion stabilized by polyoxyethylene-type nonionic surfactants. AB - To formulate a compatible green medium for the conversion of a hydrophobic substrate by a hydrophilic enzyme, we investigated the phase behavior of pseudo ternary hydrophobic ionic liquid (HIL)/buffer/polyoxyethylene-type nonionic surfactant (CnEm)/n-alcohol system and the effects of the components on the formulation of the HIL-based bicontinuous microemulsion. It is found that small head group of the surfactant, high concentration of n-alcohol (medium/long alkyl chain) and low cohesive energy density of the HIL result in low phase transition temperature. In the CnEm stabilized compatible bicontinuous microemulsion, the kinetics of laccase catalyzed oxidation of 2,6-dimethoxyphenol were also investigated. It is found that in addition to temperature, n-alcohol is the key parameter affecting the catalytic performance of laccase, and the optimum n alcohol depends on the type of HIL as an oil phase. All the kinetic parameters, such as Km, kcat, kcat/Km, and Ea (apparent activation energy), indicate that the bicontinuous microemulsion consisting of [Omim]NTf2/buffer/CnEm/n-hexanol is a suitable medium for the laccase-catalyzed reaction. To the best of our knowledge, this is the first report on the formulation of HIL-based bicontinuous microemulsion for enzyme catalysis. PMID- 26686345 TI - Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the betaIII isotype of tubulin. AB - The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the beta subunit. There are many isotypes of beta tubulin and their distributions differ among different tissues. The betaIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on betaIII but not on the other isotypes. In the current study, we tested the toxicity and the anti tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB 231 over-expressing betaIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol(r) in vivo. Although the betaIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development. PMID- 26686359 TI - Consumption of onion juice modulates oxidative stress and attenuates the risk of bone disorders in middle-aged and post-menopausal healthy subjects. AB - Osteoporosis is a chronic inflammatory condition that is characterized by the loss of bone mineral density (BMD). The current study was undertaken to evaluate the impact of onion juice intake on the bone mineral density (BMD) and bone loss in corroboration with antioxidant effects in human (in vivo) as well as inhibitory effects on the differentiation of osteoclasts in the cell line (in vitro). For in vitro studies, the RAW 264.7 (osteoclast progenitor) cells were used to examine the anti-osteoclastogenic effect of onion. In the case of in vivo studies, twenty-four subjects were divided into two groups and advised to intake 100 mL of onion juice or placebo for 8 weeks. Anthropometric measurements and blood samples were collected at the initial, 2(nd), 6(th), 8(th) and 10(th) week. The result of in vitro studies indicated that onion extract would effectively inhibit the osteoclastogenesis and its differentiation. Significant changes in the levels of alkaline phosphatase (ALP), free radicals, total antioxidant capacity (TEAC) and various antioxidants were observed in onion administered subjects. The BMD of three postmenopausal women was also found to be mildly improved on supplementation with onion juice. Onion juice consumption showed a positive modulatory effect on the bone loss and BMD by improving antioxidant activities and thus can be recommended for treating various bone-related disorders, especially osteoporosis. PMID- 26686360 TI - Collagen-Poly(N-isopropylacrylamide) Hydrogels with Tunable Properties. AB - There is a lack of hydrogel materials whose properties can be tuned at the point of use. Biological hydrogels, such as collagen, gelate at physiological temperatures; however, they are not always ideal as scaffolds because of their low mechanical strength. Their mechanics can be improved through cross-linking and chemical modification, but these methods still require further synthesis. We have demonstrated that by combining collagen with a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), the mechanical properties can be improved while maintaining cytocompatibility. Furthermore, different concentrations of this polymer led to a range of hydrogels with shear moduli ranging from 10(5) Pa down to less than 10(2) Pa, similar to the soft tissues in the body. In addition to variable mechanical properties, the hydrogel blends have a range of micron scale structures and porosities, which caused adipose-derived stromal cells (ADSCs) to adopt different morphologies when encapsulated within and may therefore be able to direct cell fate. PMID- 26686361 TI - Clostridium difficile Infections in Veterans Health Administration Long-Term Care Facilities. AB - OBJECTIVE: A nationwide initiative was implemented in February 2014 to decrease Clostridium difficile infections (CDI) in Veterans Affairs (VA) long-term care facilities. We report a baseline of national CDI data collected during the 2 years before the Initiative. METHODS: Personnel at each of 122 reporting sites entered monthly retrospective CDI case data from February 2012 through January 2014 into a national database using case definitions similar to those used in the National Healthcare Safety Network Multidrug-Resistant Organism/CDI module. The data were evaluated using Poisson regression models to examine infection occurrences over time while accounting for admission prevalence and type of diagnostic test. RESULTS: During the 24-month analysis period, there were 100,800 admissions, 6,976,121 resident days, and 1,558 CDI cases. The pooled CDI admission prevalence rate (including recurrent cases) was 0.38 per 100 admissions, and the pooled nonduplicate/nonrecurrent community-onset rate was 0.17 per 100 admissions. The pooled long-term care facility-onset rate and the clinically confirmed (ie, diarrhea or evidence of pseudomembranous colitis) long term care facility-onset rate were 1.98 and 1.78 per 10,000 resident days, respectively. Accounting for diagnostic test type, the long-term care facility onset rate declined significantly (P=.05), but the clinically confirmed long-term care facility-onset rate did not. CONCLUSIONS: VA long-term care facility CDI rates were comparable to those in recent reports from other long-term care facilities. The significant decline in the long-term care facility-onset rate but not in the clinically confirmed long-term care facility-onset rate may have been due to less testing of asymptomatic patients. Efforts to decrease CDI rates in long-term care facilities are necessary as part of a coordinated approach to decrease healthcare-associated infections. PMID- 26686362 TI - A randomized phase II study of radiation induced immune boost in operable non small cell lung cancer (RadImmune trial). AB - BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer. METHODS/DESIGN: This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. DISCUSSION: This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment. TRIAL REGISTRATION: NCT02319408; REGISTRATION: December 29, 2014. PMID- 26686363 TI - Phase analysis of gated blood pool SPECT for multiple stress testing assessments of ventricular mechanical dyssynchrony in a tachycardia-induced dilated cardiomyopathy canine model. AB - BACKGROUND: Stress-induced dyssynchrony has been shown to be independently correlated with clinical outcomes in patients with dilated cardiomyopathy (DCM) and narrow QRS complexes. However, the extent to which stress levels affect inter and intraventricular dyssynchrony parameters remains unknown. METHODS: Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction (EF) of 35% or less. Stress was then induced in DCM dogs by administering intravenous dobutamine up to a maximum of 20 MUg.kg-1.min-1. Hemodynamic and ventricular dyssynchrony data were analyzed by left ventricular (LV) pressure measurements and gated blood pool SPECT (GBPS) imaging. In order to assess mechanical dyssynchrony in DCM subjects and compare it with that of 8 normal counterparts, we extracted the following data: count-based indices of LV contraction homogeneity index (CHI), entropy and phase standard deviation, and interventricular dyssynchrony index. RESULTS: A significant LV intraventricular dyssynchrony (CHI: 96.4 +/- 1.3% in control vs 78.6% +/- 10.9% in DCM subjects) resulted in an intense LV dysfunction in DCM subjects (EF: 49.5% +/- 8.4% in control vs 22.6% +/- 6.0% in DCM), compared to control subjects. However, interventricular dyssynchrony did not vary significantly between the two groups. Under stress, DCM subjects showed a significant improvement in ventricular functional parameters at each level (EF: 22.6% +/- 6.0% at rest vs 48.1% +/- 5.8% at maximum stress). All intraventricular dyssynchrony indices showed a significant increase in magnitude of synchrony from baseline to stress levels of greater than or equal to 5 MUg.kg-1.min-1 dobutamine. There were individual differences in the magnitude and pattern of change in interventricular dyssynchrony during the various levels of stress. CONCLUSIONS: Based on GBPS analyses, different levels of functional stress, even in close intervals, can have a significant impact on hemodynamic and intraventricular dyssynchrony parameters in a DCM model with narrow QRS complex. PMID- 26686366 TI - Ammonia threshold for inhibition of anaerobic digestion of thin stillage and the importance of organic loading rate. AB - Biogas production from nitrogen-rich feedstock results in release of ammonia (NH3), causing inhibition of the microbial process. The reported threshold ammonia value for stable biogas production varies greatly between studies, probably because of differences in operating conditions. Moreover, it is often difficult to separate the effect of ammonia inhibition from that of organic loading rate (OLR), as these two factors are often interrelated. This study attempted to distinguish the effects of ammonia and OLR by analysis of two laboratory-scale biogas reactors operating with thin stillage and subjected to an increase in free ammonia (from 0.30 to 1.1 g L(-1)) either by addition of an external nitrogen source (urea) or by increasing the OLR (3.2-6.0 g volatile solids L(-1) d(-1)). The results showed that ammonia concentration was detrimental for process performance, with the threshold for stability in both processes identified as being about 1 g NH3-N L(-1), irrespective of OLR. Analysis of the methanogenic community showed limited differences between the two reactors on order level and a clear increase in the abundance of Methanomicrobiales, particularly Methanoculleus sp., in response to increasing ammonia concentration. Further comprehensive molecular analysis revealed that diverse Methanoculleus species dominated in the reactors at a given ammonia level at different OLR. The acetogenic community was clearly affected by both ammonia concentration and OLR, suggesting that the volatile fatty acid load in relation to the higher OLR was important for the dynamics of this community. PMID- 26686367 TI - Pelvic enthesopathy on CT is significantly more prevalent in patients with diffuse idiopathic skeletal hyperostosis (DISH) compared with matched control patients. AB - The purpose of this study is to evaluate the prevalence of pelvic enthesopathy on computed tomography (CT) in patients with DISH compared to matched control group. Pelvic CT examinations of patients with DISH (Resnick criteria) were retrospectively evaluated for the presence of enthesophytes at four entheseal sites bilaterally: ischial tuberosity, pubis, greater trochanter, and anterior superior iliac spine (ASIS). This was compared with age- and gender-matched control group of consecutive patients with <2 flowing osteophytes on CT along the entire spine. Multivariate analysis of variance (ANOVA) was applied to examine the degree of difference between pelvic enthesopathy in DISH patients and controls and to estimate the potential predictive ability of the different findings. Logistic regression analysis was used to estimate the odds ratio of the studied findings. Pelvic CTs of 210 patients (149:61, M:F; average age, 72.3 years) were evaluated: DISH group, 104 patients (74:30, M:F); matched control group, 106 patients (75:31, M:F). Mean total and local enthesopathy scores were significantly higher in the DISH group compared with the control group (total 5.03:1.9; ASIS 1.58:0.55; pubis 0.94:0.36; ischial tuberosity 1.47:0.76; greater trochanter 1.04:0.24; p < 0.001). ASIS and greater trochanter enthesophytes were the most robust contributors that significantly distinguished between patients with DISH and those without DISH. Prominent enthesophytes were more common among DISH patients (DISH:controls, 52:13, p = 0.02). Prominent pelvic enthesophytes detected on CT have a strong discriminating power between DISH and non-DISH patients. Results imply that pelvic enthesopathy may be included in the radiographic criteria for DISH. PMID- 26686368 TI - Overweight older adults, particularly after an injury, are at high risk for accelerated knee osteoarthritis: data from the Osteoarthritis Initiative. AB - We explored whether age and body mass index (BMI) can help identify a subset of individuals who are at high risk for accelerated knee osteoarthritis (AKOA) compared with common knee osteoarthritis (KOA). In the Osteoarthritis Initiative, a multicenter observational cohort study of KOA (n = 4796), we studied participants without KOA at baseline (Kellgren-Lawrence (KL) <2). Participants could have one of three outcomes: (1) AKOA, >=1 knee progressed to end-stage KOA within 48 months; (2) common KOA, >=1 knee increased in radiographic scoring within 48 months (excluding those with AKOA); and (3) no KOA, no change in KL grade in either knee. After verifying an interaction between age, BMI, and recent knee injury, we determined if we could identify a specific subset of individuals at high risk for AKOA instead of KOA. First, we reviewed three-dimensional graphs with age, BMI, and probability of AKOA versus KOA on the axes. We then conducted a logistic regression with AKOA as the outcome and age-BMI groups as the predictor. In our main analyses, we found that older individuals with a BMI <35 kg/m(2) were more likely to develop AKOA than common KOA (n = 64; mean [SD] BMI = 27.3 [3.1] kg/m(2); odds ratio = 3.47, 95 % confidence interval = 1.70 to 7.10), especially if they had a recent knee injury. While older age and greater BMI are independently associated with AKOA, we found that older individuals who had a higher BMI, particularly if they have an injury, were more likely to develop AKOA than common KOA. PMID- 26686369 TI - Waon therapy attenuates cardiac hypertrophy and promotes myocardial capillary growth in hypertensive rats: a comparative study with fluvastatin. AB - Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 degrees C for 15 min followed by 34 degrees C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-beta1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin. PMID- 26686370 TI - The efficacy of everolimus-eluting stent implantation in patients with ST-segment elevation myocardial infarction: outcomes of 2-year clinical follow-up. AB - First-generation drug-eluting stents (DES) demonstrated delay in vascular healing and increase in incidence of late and very late stent thrombosis compared with bare-metal stents (BMS). Second-generation DES, however, have shown a reduction of late and very late stent thrombosis compared with first-generation DES. Thus, we decided to evaluate whether the second-generation everolimus-eluting stent (EES) has an advantage over BMS in Japanese patients with ST-segment elevation myocardial infarction (STEMI). This study was conducted in two centers, retrospective, non-randomized and observational design in patients with STEMI. Three-hundred eighty patients were randomly selected to receive EES (198 patients) or cobalt-chromium BMS (182 patients). The primary endpoints were cardiac death, recurrent myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis (ST). At 2 years, the rates of TLR, TVR, and recurrent MI were significantly lower in the EES group than in the BMS group (TLR 1.5 vs. 8.3 %, p < 0.05; TVR 2.5 vs. 9.4 %, p < 0.05; recurrent MI 1.0 vs. 4.1 %, p < 0.05), and the rate of ST was also significantly lower in the EES group than in the BMS group (0.5 vs. 4.3 %, p < 0.05). Thus, major adverse cardiac events defined at the composite cardiac death, MI, TLR, TVR, or ST were significantly lower in EES group than in BMS group (3.0 vs. 9.9 %, p = 0.008). The rate of cardiac death, however, did not differ between both groups. In STEMI patients, EES may be associated with improved outcomes-specifically, a significant reduction in TVR, ST, and recurrent MI compared to BMS throughout 2 years. PMID- 26686371 TI - Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats. AB - Cardiac function is one important determinant to maintain tissue oxygenation and is thus highly regulated. In this context, it is interesting that centrally mediated opioidergic influence on cardiac function has long been known. Only recently, KOR and DOR have been found to be expressed in healthy left ventricular myocardium in rats and colocalized with parts of the excitation-contraction coupling system. However, several comments in literature exist doubting the existence of MOR in cardiac tissue. We, therefore, aimed to detect MOR in rat left ventricular cardiomyocytes, and to evaluate whether MOR and POMC are regulated during heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics and the existence of MOR and POMC was investigated by means of radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Membrane MOR selective binding sites were detected in the left ventricular myocardium, however, they were lower in abundance than KOR- and DOR specific binding sites and B max of MOR could not be determined. In left ventricular cardiomyocytes, MOR colocalized with parts of the excitation-coupling mechanism, e.g., Cav1.2 of the cell membrane and invaginated T-tubules as well as the ryanodine receptor of the sarcoplasmatic reticulum. More importantly, MOR strongly colocalized with mitochondria of left ventricular cardiomyocytes. Volume overload was not associated with an altered expression of MOR and POMC on both mRNA and protein level. These findings provide evidence for the existence of MOR on the cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular cardiomyocytes in rats. However, heart failure does not result in an altered expression of the cardiac MOR-opioid system. Thus, MOR agonist treatment commonly used in the clinical setting-might directly affect cardiac function, which needs to be evaluated in greater detail in the near future. PMID- 26686372 TI - Effect of a cardiac rehabilitation program on exercise oscillatory ventilation in Japanese patients with heart failure. AB - Although exercise oscillatory ventilation has emerged as a potent independent risk factor for adverse prognosis in heart failure, it is not well known whether cardiac rehabilitation can improve oscillatory ventilation. In this study, we investigated the magnitude of oscillations in ventilation before and after cardiac rehabilitation in chronic heart failure patients with exercise oscillatory ventilation. Cardiac rehabilitation (5-month program) was performed in 26 patients with chronic heart failure who showed an oscillatory ventilation pattern during cardiopulmonary exercise testing (CPX). After the 5-month rehabilitation program was completed, the patients again underwent CPX. To determine the magnitude of oscillations in ventilation, the amplitude and cycle length of the oscillations were calculated and compared with several other parameters, including biomarkers that have established prognostic value in heart failure. At baseline before cardiac rehabilitation, both oscillation amplitude (R = 0.625, P < 0.01) and cycle length (R = 0.469, P < 0.05) were positively correlated with the slope of minute ventilation vs. carbon dioxide production. Plasma BNP levels were positively correlated with amplitude (R = 0.615, P < 0.01) but not cycle length (R = 0.371). Cardiac rehabilitation decreased oscillation amplitude (P < 0.01) but failed to change cycle length. The change in amplitude was positively correlated with the change in BNP levels (R = 0.760, P < 0.01). Multiple regression analysis showed that only the change in amplitude was an independent predictor of the change in BNP levels (R = 0.717, P < 0.01). A 5 month cardiac rehabilitation program improves exercise oscillatory ventilation in chronic heart failure patients by reducing the oscillation amplitude. This effect is associated with a reduction of plasma BNP levels, potentially contributing to an improvement of heart failure. PMID- 26686374 TI - Raman spectroscopic features of the neutral vacancy in diamond from ab initio quantum-mechanical calculations. AB - Quantum-mechanical ab initio calculations are performed to elucidate the vibrational spectroscopic features of a common irradiation-induced defect in diamond, i.e. the neutral vacancy. Raman spectra are computed analytically through a Coupled-Perturbed-Hartree-Fock/Kohn-Sham approach as a function of both different defect spin states and defect concentration. The experimental Raman features of defective diamond located in the 400-1300 cm(-1) spectral range, i.e. below the first-order line of pristine diamond at 1332 cm(-1), are well reproduced, thus corroborating the picture according to which, at low damage densities, this spectral region is mostly affected by non-graphitic sp(3) defects. No peaks above 1332 cm(-1) are found, thus ruling out previous tentative assignments of different spectral features (at 1450 and 1490 cm(-1)) to the neutral vacancy. The perturbation introduced by the vacancy to the thermal nuclear motion of carbon atoms in the defective lattice is discussed in terms of atomic anisotropic displacement parameters (ADPs), computed from converged lattice dynamics calculations. PMID- 26686373 TI - Baseline polyp size as a potential predictive factor for recurrence of polypoidal choroidal vasculopathy. AB - PURPOSE: To investigate the predictive factors for recurrence of polypoidal choroidal vasculopathy (PCV). METHODS: The medical records of 78 consecutive patients (78 eyes) with treatment-naive PCV who responded to first-line treatment and completed at least a 3-year follow-up after the first remission were retrospectively analyzed. In this comparative cohort study, baseline characteristics were compared between the patients who had at least one recurrence (the recurrence group) and those without recurrence (the non recurrence group) during at least 3-year follow-up periods. In addition, possible predictive factors for recurrence of PCV were investigated by using Cox regression analysis. RESULTS: Within 3 years of the first remission, 50 eyes (64 %) showed at least one recurrence (mean 1.5; 1 to ~2 times). There were no significant differences in the baseline characteristics between the recurrence group and the non-recurrence group. However, the largest polyp diameter was significantly different: the mean largest polyp diameter (524 +/- 340 MUm) was significantly larger in the recurrence group compared to that of the non recurrence group (352 +/- 173 MUm; P = 0.038). Cox regression analysis showed that the largest polyp diameter at baseline significantly correlated with recurrence of PCV (B = 1.470, P = 0.015). CONCLUSIONS: The largest polyp diameter at baseline may be predictive for PCV recurrence, as it was significantly larger in patients who had at least one recurrence. PMID- 26686375 TI - Patterns of esophageal pressure responses to a rapid drink challenge test in patients with esophageal motility disorders. AB - BACKGROUND: Multiple rapid swallow has been proposed as a challenge test that can help diagnosis and management of patients with esophageal motility disorders. Our aim was to characterize specific pressure patterns in response to a rapid drink challenge test in patients with esophageal motility disorders, and to determine the potential of these patterns in the diagnosis of patients with esophageal symptoms but normal single swallow manometry. METHODS: Pressure responses to a rapid drink challenge test (rapid swallow of 200 mL water) were prospectively analyzed in 30 healthy controls and 285 patients with esophageal symptoms: 33 achalasia, 68 hypocontractile motility, 27 hypercontractile motility and 160 patients with normal manometry. KEY RESULTS: Three different patterns of responses were characterized: (i) hypopressive or normal pattern that was shared by healthy subjects and patients with hypocontractile peristalsis, and discriminated patients with non-obstructive hypercontractile motility or achalasia (p < 0.001; sensitivity 80% and specificity 93%), (ii) brief hyperpressive pattern observed in patients with non-obstructive hypercontractile disorders (distal spasm and hypercontractile esophagus), and (iii) prolonged hyperpressive pattern, that discriminated achalasia from patients with non obstructive hypercontractile disorders (p < 0.001; sensitivity 70% and specificity 85%). Seventeen percent of patients with esophageal symptoms but normal single swallow manometry had abnormal responses to the drink challenge test: 14% a brief hyperpressive pattern, and 3% a prolonged hyperpressive pattern. CONCLUSIONS & INFERENCES: Specific patterns of responses to a rapid drink challenge test could help identification of motility disorders in patients with esophageal symptoms but unclear or normal esophageal manometry. PMID- 26686377 TI - Construction of supramolecular polymer by enzyme-triggered covalent condensation of CB[8]-FGG-based supramonomer. AB - A rapid and effective enzymatic strategy for the fabrication of a supramolecular polymer is presented for the first time, in which a bifunctional ternary host guest supramonomer is first prepared followed by subsequent enzymatic coupling of supramonomers. PMID- 26686376 TI - Examining the mediating roles of binge eating and emotional eating in the relationships between stress and metabolic abnormalities. AB - To test whether binge eating and emotional eating mediate the relationships between self-reported stress, morning cortisol and the homeostatic model of insulin resistance and waist circumference. We also explored the moderators of gender and age. Data were from 249 adults (mean BMI = 26.9 +/- 5.1 kg/m(2); mean age = 28.3 +/- 8.3 years; 54.2% male; 69.5% white) recruited from the community who were enrolled in a cross-sectional study. Participants completed a comprehensive assessment panel of psychological and physiological assessments including a morning blood draw for plasma cortisol. We found negative relationships between stress and morning cortisol (r = -0.15 to -0.21; p < 0.05), and cortisol and the homeostatic model of insulin resistance and waist circumference (r = -0.16, -0.25, respectively; p < 0.05). There was not statistical support for binge eating or emotional eating as mediators and no support for moderated mediation for either gender or age; however, gender moderated several paths in the model. These include the paths between perceived stress and emotional eating (B = 0.009, p < 0.001), perceived stress and binge eating (B = 0.01, p = 0.003), and binge eating and increased HOMA-IR (B = 0.149, p = 0.018), which were higher among females. Among women, perceived stress may be an important target to decrease binge and emotional eating. It remains to be determined what physiological and psychological mechanisms underlie the relationships between stress and metabolic abnormalities. PMID- 26686379 TI - Investigation of mutual aerobic and lower limb muscular activity during cycling. AB - The evaluation of physical activity is a complex task that requires performing an analysis of muscular activity and aerobic/anaerobic threshold and it is often difficult to observe and propose a single method. The purpose of the article is to evaluate a relation between aerobic capacity and activity of lower limb muscles via changes of muscle's EMG signal during physical, sub-maximal veloergometric loading. The activity parameters of 5 lower limb muscles such as semitendinosus, rectus femoris, biceps femoris, gastrocnemius medialis, and tibialis anterior were measured and analyzed during the veloergometric exercise tests and the heart rate and the aerobic capacity were estimated from registered data. The obtained aerobic parameters allow setting an individual and overall voluntary physical capacity. The regression oxygen function presented allows analyzing and predicting the ability of subjects to generate energy while maintaining muscle activity during the exercise. The correlation between the consumption of oxygen and constant physical loading time is determined. It was found that comparing VO2max capabilities the physical effort in the male group was 16% higher than in women. Oxygen consumption and maximum muscle effort dependency on the load time was established. It was observed that the maximal muscular effort appeared before VO2max reached maximal limit in both groups. The maximal oxygen consumption is achieved in the middle or sometimes at the beginning (depending on load) of exercise while maximal muscular effort was found in several phases of cycling: at the beginning and at the end of loading time. PMID- 26686378 TI - Priming tool actions: Are real objects more effective primes than pictures? AB - Humans are faster to grasp an object such as a tool if they have previewed the same object beforehand. This priming effect is strongest when actors gesture the use of the tool rather than simply move it, possibly because the previewed tool activates action-specific routines in dorsal-stream motor networks. Here, we examined whether real tools, which observers could physically act upon, serve as more potent primes than two-dimensional images of tools, which do not afford physical action. Participants were presented with a prime stimulus that could be either a real tool or a visually matched photograph of a tool. After a brief delay, participants interacted with a real tool target, either by 'grasping to move,' or 'grasping to use' it. The identities of the prime and target tools were either the same (congruent trials; e.g., spatula-spatula) or different (incongruent trials; e.g., whisk-spatula). As expected, participants were faster to initiate grasps during trials when they had to move the tool rather than gesture its use. Priming effects were observed for grasp-to-use, but not grasp-to move, responses. Surprisingly, however, both pictures of tools and real tools primed action responses equally. Our results indicate that tool priming effects are driven by pictorial cues and their implied actions, even in the absence of volumetric cues that reflect the tangibility and affordances of the prime. PMID- 26686380 TI - Extracorporeal Shock Wave Therapy for Digital Ulcers of Systemic Sclerosis: A Phase 2 Pilot Study. AB - Patients with systemic sclerosis (SSc) often display Raynaud's phenomenon and digital skin ulcers. As these ulcers are not associated with autoimmune factors or abnormal coagulation, conventional immunosuppressive therapies, vasodilators, and anticoagulants are often ineffective. Here, we used extracorporeal shock wave therapy (ESWT) to treat these ulcers. Nine SSc patients with new digital ulcers, previously treated with at least one currently available vasodilator or anticoagulant were enrolled. One ESWT session consisted of 100 pulses at 0.08 0.25 mJ/mm(2) in 20 areas on both hands and 15 areas on both feet, totaling 7,000 pulses. Treatment was performed once per week for 9 weeks with observations over 20 weeks. Outcomes were evaluated according to the number and diameter of ulcers, Rodnan skin score, Health Assessment Questionnaire (HAQ), EuroQol 5 dimensions (EQ-5D), visual analog scale for pain, and the PainVision system. The surface skin temperature of all the fingers was measured using thermography. Ulcers showed signs of healing after one session, and their mean number decreased from 5.4 to 1.1 at 9 weeks. In particular, of the 18 large ulcers (> 5 mm) observed in 7 patients before the treatment, 10 disappeared and the rest became smaller; namely, the mean size decreased from 10.9 mm to 2.5 mm at 20 weeks. The average scores on the HAQ, EQ-5D, and PainVision system also improved. Treatment was minimally invasive and could be repeated without any adverse effects. ESWT may be added to standard treatments for indolent digital ulcers of SSc, as an effective and safe method. PMID- 26686381 TI - Expression of TGF-beta1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice. AB - Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-beta1 (TGF beta1), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (alpha-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF beta1 expression peaked at 1 week after denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGF- and alpha-SMA-positive muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-beta1 and CTGF may be involved in the process of denervated skeletal muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of alpha-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies. PMID- 26686382 TI - Phase transition kinetics of LiNi0.5Mn1.5O4 analyzed by temperature-controlled operando X-ray absorption spectroscopy. AB - LiNi0.5Mn1.5O4 (LNMO) is a promising positive electrode material for lithium ion batteries because it shows a high potential of 4.7 V vs. Li/Li(+). Its charge discharge reaction includes two consecutive phase transitions between LiNi0.5Mn1.5O4 (Li1) <-> Li0.5Ni0.5Mn1.5O4 (Li0.5) and Li0.5 <-> Ni0.5Mn1.5O4 (Li0) and the complex transition kinetics that governs the rate capability of LNMO can hardly be analyzed by simple electrochemical techniques. Herein, we apply temperature-controlled operando X-ray absorption spectroscopy to directly capture the reacting phases from -20 degrees C to 40 degrees C under potential step (chronoamperometric) conditions and evaluate the phase transition kinetics using the apparent first-order rate constants at various temperatures. The constant for the Li1 <-> Li0.5 transition (process 1) is larger than that for the Li0.5 <-> Li0 transition (process 2) at all the measured temperatures, and the corresponding activation energies are 29 and 46 kJ mol(-1) for processes 1 and 2, respectively. The results obtained are discussed to elucidate the limiting factor in this system as well as in other electrode systems. PMID- 26686383 TI - Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines. AB - The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of indolines with disulfides and diselenides were developed. This protocol relies on the use of a removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance. PMID- 26686384 TI - Single-stage endovascular treatment of subarachnoid hemorrhage related to bilateral vertebral artery dissecting aneurysms. AB - OBJECTIVE: Treatment of bilateral vertebral artery dissecting aneurysms presenting with subarachnoid hemorrhage remains challenging as bilateral deconstructive procedures may not be feasible. In this case series, we describe our approach to their management and review the pertinent literature. METHOD: A retrospective review of our prospectively collected database on aneurysms was performed to identify all patients with acute subarachnoid hemorrhage in the setting of bilateral intradural vertebral artery dissections (VAD) encompassing a period from January 2000 and March 2012. RESULT: Four patients (M/F = 2/2; mean age, 51.5 years) were identified. In two cases the site of rupture could be identified by angiographic and cross-sectional features; in these patients deconstructive treatment (proximal obliteration or trapping) of the ruptured site and reconstructive treatment of the unruptured site (using stents and coils) were performed. In the patients in whom the site of hemorrhage could not be determined, bilateral reconstructive treatment was performed. No treatment related complications were encountered. Modified Rankin scale scores were 0-1 at discharge, and on follow-up (mean 63 months), no recurrence, in-stent thrombosis or new neurological deficits were encountered. CONCLUSION: We believe that single stage treatment in patients with bilateral VAD is indicated: If the site of hemorrhage can be determined, we prefer deconstructive treatment on the affected site and reconstructive treatment on the non-affected site to prevent increased hemodynamic stress on the unruptured but diseased wall. If the site of dissection cannot be determined, we prefer bilateral reconstructive treatment to avoid increasing hemodynamic stress on the potentially untreated acute hemorrhagic dissection. PMID- 26686385 TI - Development of an Interleukin-1beta Vaccine in Patients with Type 2 Diabetes. AB - Interleukin-1beta (IL-1beta) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1beta activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1beta. The vaccine hIL1bQb consisting of full-length, recombinant IL 1beta coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1beta specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL 1beta-specific antibody responses were detectable after six injections with doses of 900 ug. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1beta and represents a new treatment option for IL-1beta-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105). PMID- 26686386 TI - Combination wt-p53 and MicroRNA-125b Transfection in a Genetically Engineered Lung Cancer Model Using Dual CD44/EGFR-targeting Nanoparticles. AB - Mutations in KRAS and p53 signaling pathways contribute to loss of responsiveness to current therapies and a decreased survival in lung cancer. In this study, we have investigated the delivery and transfection of wild-type (wt-) p53 and microRNA-125b (miR-125b) expressing plasmid DNA, in SK-LU-1 human lung adenocarcinoma cells as well as in Kras(G12D)/p53(fl/fl) (KP) genetically engineered mouse model of lung cancer. Systemic plasmid DNA delivery with dual CD44/EGFR-targeted hyaluronic acid (HA)-based nanoparticles (NPs) resulted in a 2 to 20-fold increase in wt-p53 and miR-125b gene expression in SK-LU-1 cells. This resulted in enhanced apoptotic activity as seen with increased APAF-1 and caspase-3 gene expression. Similarly, in vivo evaluations in KP mouse model indicated successful CD44/EGFR-targeted delivery. Tumor growth inhibition and apoptotic induction were also observed with (wt-p53+miR125b) combination therapy in KP tumor model. Lastly, J774.A1 murine macrophages co-cultured with transfected SK-LU-1 cells showed a 14- to 35-fold increase in the iNOS-Arg-1 ratio, supportive of previous results demonstrating a role of miR-125b in macrophage repolarization. Overall, these results show tremendous promise of wt p53 and miR-125b gene therapy using dual CD44/EGFR-targeting HA NP vector for effective treatment of lung cancer. PMID- 26686388 TI - Modulation of the antioxidant nuclear factor (erythroid 2-derived)-like 2 pathway by antidepressants in rats. AB - Patients with major depression who are otherwise medically healthy have activated inflammatory pathways in their organism. It has been described that depression is not only escorted by inflammation but also by induction of multiple oxidative/nitrosative stress pathways. Nevertheless, there are finely regulated mechanisms involved in preserving cells from damage, such as the antioxidant nuclear transcription factor Nrf2. We aim to explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze whether antidepressants affect the antioxidant activity of the Nrf2 pathway. Male Wistar rats were exposed to chronic mild stress (CMS) and some of them were treated with desipramine, escitalopram or duloxetine. We studied the expression of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS. After CMS, there is an inhibition of upstream and downstream elements of the Nrf2 pathway in the PFC (e.g. PI3K/Akt, GPx...). Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the CMS. However, in the hippocampus, Nrf2 pathways are not that affected and antidepressants do not have many actions. In conclusion, Nrf2 pathway is differentially regulated by antidepressants in the PFC and hippocampus. The Nrf2 pathway is involved in the oxidative/nitrosative damage detected in the PFC and antidepressants have a therapeutic action through this pathway. However, it seems that Nrf2 is not involved in the effects caused by CMS in the hippocampus. PMID- 26686387 TI - Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation. AB - DNA hypermethylation is extensively explored as therapeutic target for gene expression modulation in cancer. Here, we re-activated hypermethylated candidate tumor suppressor genes (TSGs) (C13ORF18, CCNA1, TFPI2, and Maspin) by TET2 induced demethylation in cervical cancer cell lines. To redirect TET2 to hypermethylated TSGs, we engineered zinc finger proteins (ZFPs), which were first fused to the transcriptional activator VP64 to validate effective gene re expression and confirm TSG function. ChIP-Seq not only revealed enriched binding of ZFPs to their intended sequence, but also considerable off-target binding, especially at promoter regions. Nevertheless, results obtained by targeted re expression using ZFP-VP64 constructs were in line with cDNA overexpression; both revealed strong growth inhibition for C13ORF18 and TFPI2, but not for CCNA1 and Maspin. To explore effectivity of locus-targeted demethylation, ZFP-TET2 fusions were constructed which efficiently demethylated genes with subsequent gene re activation. Moreover, targeting TET2 to TFPI2 and C13ORF18, but not CCNA1, significantly decreased cell growth, viability, and colony formation in cervical cancer cells compared to a catalytically inactive mutant of TET2. These data underline that effective re-activation of hypermethylated genes can be achieved through targeted DNA demethylation by TET2, which can assist in realizing sustained re-expression of genes of interest. PMID- 26686389 TI - Chronic administration of a melatonin membrane receptor antagonist, luzindole, affects hippocampal neurogenesis without changes in hopelessness-like behavior in adult mice. AB - Melatonin is involved in the regulation of hippocampal neuronal development during adulthood. Emerging evidence indicates that exogenous melatonin acts during different events of the neurogenic process and exerts antidepressant-like behavior in rodents. Thus, melatonin might act through different mechanism, including acting as an antioxidant, interacting with intracellular proteins and/or activating membrane receptors. The melatonin membrane receptors (MMRs; Mt1/Mt2) are distributed throughout the hippocampus with an interesting localization in the hippocampal neurogenic microenvironment (niche), suggesting the involvement of these receptors in the beneficial effects of melatonin on hippocampal neurogenesis and behavior. In this study, we analyzed the participation of MMRs in the baseline neurogenesis in C57BL/6 mice. To this end, we used a pharmacological approach, administering luzindole (10 mg/kg) for 14 days. We observed a decrease in the absolute number of doublecortin-positive cells (49%) without changes in either the dendrite complexity of mature doublecortin-cells or the number of apoptotic cells (TUNEL). However, after the chronic administration of luzindole, cell proliferation (Ki67) significantly decreased (36%) with increasing (>100%) number of neural stem cells (NSCs; GFAP(+)/Sox2(+)) in the subgranular zone of the dentate gyrus of the hippocampus. In addition, luzindole did not affect hopelessness-like behavior in the forced swim test (FST) or changes in the novelty suppressed feeding test (NST) after 14 days of treatment either neuronal activation in the dentate gyrus after FST. These results suggest that the MMRs are involved in the effects of endogenous melatonin to mediate the transition from NSCs and proliferative cells to the following developmental stages implicated in the hippocampal neurogenic process of adult female C57BL/6 mice. PMID- 26686390 TI - Translational neurophysiological markers for activity of the metabotropic glutamate receptor (mGluR2) modulator JNJ-40411813: Sleep EEG correlates in rodents and healthy men. AB - Alterations in rapid eye movement sleep (REM) have been suggested as valid translational efficacy markers: activation of the metabotropic glutamate receptor 2 (mGluR2) was shown to increase REM latency and to decrease REM duration. The present paper addresses the effects on vigilance states of the mGluR2 positive allosteric modulator (PAM) JNJ-40411813 at different circadian times in rats and after afternoon dosing in humans. Due to its dual mGluR2 PAM/serotonin 2A (5 HT2A) receptor antagonism in rodents, mGlu2R specificity of effects was studied in wild-type (WT) and mGluR2 (-/-) mice. 5-HT2A receptor occupancy was determined in humans using positron emission tomography (PET). Tolerance development was examined in rats after chronic dosing. EEG oscillations and network connectivity were assessed using multi-channel EEG. In rats, JNJ-40411813 increased deep sleep time and latency of REM onset but reduced REM time when administered 2 h after 'lights on' (CT2): this was sustained after chronic dosing. At CT5 similar effects were elicited, at CT10 only deep sleep was enhanced. Withdrawal resulted in baseline values, while re-administration reinstated drug effects. Parieto occipital cortical slow theta and gamma oscillations were correlated with low locomotion. The specificity of functional response was confirmed in WT but not mGluR2 (-/-) mice. A double-blind, placebo-controlled polysomnographic study in healthy, elderly subjects showed that 500 mg of JNJ-40411813 consistently increased deep sleep time, but had no effect on REM parameters. This deep sleep effect was not explained by 5-HT2A receptor binding, as in the PET study even 700 mg only marginally displaced the tracer. JNJ-40411813 elicited comparable functional responses in rodents and men if circadian time of dosing was taken into account. These findings underscore the translational potential of sleep mechanisms in evaluating mGluR2 therapeutics when administered at the appropriate circadian time. PMID- 26686391 TI - Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. AB - In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS 135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPgammaS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 MUM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. PMID- 26686392 TI - Bacterial translocation affects intracellular neuroinflammatory pathways in a depression-like model in rats. AB - Recent studies have suggested that depression is accompanied by an increased intestinal permeability which would be related to the inflammatory pathophysiology of the disease. This study aimed to evaluate whether experimental depression presents with bacterial translocation that in turn can lead to the TLR 4 in the brain affecting the mitogen-activated protein kinases (MAPK) and antioxidant pathways. Male Wistar rats were exposed to chronic mild stress (CMS) and the intestinal integrity, presence of bacteria in tissues and plasma lipopolysaccharide levels were analyzed. We also studied the expression in the prefrontal cortex of activated forms of MAPK and some of their activation controllers and the effects of CMS on the antioxidant Nrf2 pathway. Our results indicate that after exposure to a CMS protocol there is increased intestinal permeability and bacterial translocation. CMS also increases the expression of the activated form of the MAPK p38 while decreasing the expression of the antioxidant transcription factor Nrf2. The actions of antibiotic administration to prevent bacterial translocation on elements of the MAPK and Nrf2 pathways indicate that the translocated bacteria are playing a role in these effects. In effect, our results propose a role of the translocated bacteria in the pathophysiology of depression through the p38 MAPK pathway which could aggravate the neuroinflammation and the oxidative/nitrosative damage present in this pathology. Moreover, our results reveal that the antioxidant factor Nrf2 and its activators may be involved in the consequences of the CMS on the brain. PMID- 26686394 TI - From Twinning to Pure Zincblende Catalyst-Free InAs(Sb) Nanowires. AB - III-V nanowires are candidate building blocks for next generation electronic and optoelectronic platforms. Low bandgap semiconductors such as InAs and InSb are interesting because of their high electron mobility. Fine control of the structure, morphology, and composition are key to the control of their physical properties. In this work, we present how to grow catalyst-free InAs1-xSbx nanowires, which are stacking fault and twin defect-free over several hundreds of nanometers. We evaluate the impact of their crystal phase purity by probing their electrical properties in a transistor-like configuration and by measuring the phonon-plasmon interaction by Raman spectroscopy. We also highlight the importance of high-quality dielectric coating for the reduction of hysteresis in the electrical characteristics of the nanowire transistors. High channel carrier mobilities and reduced hysteresis open the path for high-frequency devices fabricated using InAs1-xSbx nanowires. PMID- 26686395 TI - PEDOT/PSS-Halloysite Nanotubes (HNTs) Hybrid Films: Insulating HNTs Enhance Conductivity of the PEDOT/PSS Films. AB - We have for the first time found that completely insulating Halloysite nanotubes (HNTs) significantly enhance electrical conductivity of PEDOT/PSS films by simply mixing. Based on this accident finding we have created highly porous and conductive PEDOT/PSS films hybridized with the HNTs. Through further optimization of the mixing condition we have obtained flexible and conductive hybrid films with high specific surface area. Based on experimental evidences we proposed a plausible mechanism of the phenomenon where the PEDOT/PSS colloidal particle with particle size of several tens nanometers well pack at the nano-channels into well ordered structures of PEDOT/PSS particles, which show conductivity as higher as several order of magnitude than that of PEDOT/PSS particles in outside of the HNTs. PMID- 26686393 TI - Medicinal chemistry of adenosine, P2Y and P2X receptors. AB - Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain, diabetes, ischemic protection and many other conditions. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID- 26686396 TI - Power loss mechanisms in pathological tracheas. AB - The effort required to inhale a breath of air is a critically important measure in assessing airway function. Although the contribution of the trachea to the total flow resistance of the airways is generally modest, pathological alterations in tracheal geometry can have a significant negative effect. This study investigates the mechanisms of flow energy loss in a healthy trachea and in four geometries affected by retrosternal goitre which can cause significant distortions of tracheal geometry including constriction and deviation with abnormal curvature. By separating out the component of energy loss related to the wall shear (frictional loss), striking differences are found between the patterns of energy dissipation in the normal and pathological tracheas. Furthermore the ratio of frictional to total loss is dramatically reduced in the pathological geometries. PMID- 26686397 TI - Leg joint function during walking acceleration and deceleration. AB - Although constant-average-velocity walking has been extensively studied, less is known about walking maneuvers that change speed. We investigated the function of individual leg joints when humans walked at a constant speed, accelerated or decelerated. We hypothesized that leg joints make different functional contributions to maneuvers. Specifically, we hypothesized that the hip generates positive mechanical work (acting like a "motor"), the knee generates little mechanical work (acting like a "strut"), and the ankle absorbs energy during the first half of stance and generates energy during the second half (consistent with "spring"-like function). We recorded full body kinematics and kinetics, used inverse dynamics to estimate net joint moments, and decomposed joint function into strut-, motor-, damper-, and spring-like components using indices based on net joint work. Although overall leg mechanics were primarily strut-like, individual joints did not act as struts during stance. The hip functioned as a power generating "motor," and ankle function was consistent with spring-like behavior. Even though net knee work was small, the knee did not behave solely as a strut but also showed motor-, and damper-like function. Acceleration involved increased motor-like function of the hip and ankle. Deceleration involved decreased hip motor-like function and ankle spring-like function and increased damping at the knee and ankle. Changes to joint mechanical work were primarily due to changes in joint angular displacements and not net moments. Overall, joints maintain different functional roles during unsteady locomotion. PMID- 26686398 TI - Musculo-articular stiffness is affected by the magnitude of the impulse applied when assessed with the free-oscillation technique. AB - Musculo-articular stiffness (MAS) of the triceps surae can be assessed using the free-oscillation technique whereby an impulse is applied and the ensuing damped oscillations are recorded. The purpose of this study was to investigate if impulses of different magnitudes can affect the measurement of MAS. Twenty seven males (20.7+/-1.3 years) participated in this study. Three impulses of different magnitude (1.5, 2.3 and 3.1Ns) and four different loads (10, 20, 30, 40kg) were employed in the assessment of triceps surae MAS, which was quantified and compared across loads and perturbations. As the magnitude of the impulse applied increased, the MAS (p<0.0005, ES 1.20) and natural frequency of oscillation (f) decreased while the amplitude of movement (AM), angular velocity (omega) and damping coefficient (C) increased significantly. As the load level increased, the MAS (p<0.0005, ES 2.25) and the baseline ground reaction force (BGRF) increased whereas f, AM and omega decreased significantly. Even though the effect of the load is stronger, it appears that the level of MAS recorded (ranging from 24.0 to 21.3KN/m for the 10kg load and from 32.9 to 31.0KN/m for the 40kg load, for impulse 1 and 3 respectively), including several underlying factors, are affected by the magnitude of the impulse, therefore its accurate determination is pivotal. Caution should be exercised when comparing results from previous studies where the magnitude of the impulse has only been estimated but not controlled for. PMID- 26686399 TI - Refining the tools of immunotherapy. PMID- 26686400 TI - Immunotherapy: the next step in the treatment of myeloma. PMID- 26686401 TI - Treatment-free remission after stopping second-line dasatinib. PMID- 26686402 TI - Out of the haemophagocytic lymphohistiocytosis niche. PMID- 26686403 TI - Blood transfusion in cardiac surgery: who should get transfused? PMID- 26686404 TI - Platelets: an unexploited data source in biomarker research. PMID- 26686405 TI - Focus on haematology. PMID- 26686406 TI - Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. AB - BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b-2 study, 82% of patients with relapsed multiple myeloma who were given elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results. METHODS: We did this randomised, multicentre, open-label, dose escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0-2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1 21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intention-to-treat population, and safety was analysed in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials.gov, number NCT00742560. FINDINGS: Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3-4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs. INTERPRETATION: Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress. FUNDING: Bristol-Myers Squibb, AbbVie Biotherapeutics. PMID- 26686407 TI - Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. AB - BACKGROUND: First-line imatinib treatment can be successfully discontinued in patients with chronic myeloid leukaemia after deep molecular response has been sustained for at least 2 years. We investigated the safety and efficacy of discontinuing second-line or subsequent dasatinib after at least 1 year of deep molecular response. METHODS: The Dasatinib Discontinuation trial was a prospective multicentre trial done in Japan. Eligible patients taking dasatinib and with confirmed stable deep molecular response were enrolled between April 1, 2011, and March 31, 2012. All patients received dasatinib consolidation therapy for at least 1 year. In those with sustained deep molecular response, dasatinib was discontinued. Patients were followed up every month in year 1 (clinical cutoff), every 3 months in year 2, and every 6 months in year 3 for deep molecular response and immunological profiles. The primary endpoint was the proportion of patients with treatment-free remission at 6 months after discontinuation. Molecular relapse was defined as loss of deep molecular response at any assessment. This study is registered, number UMIN000005130. FINDINGS: 88 patients were enrolled in the consolidation phase, 24 were excluded from the discontinuation phase due to fluctuations in BCR-ABL1 transcript levels. One patient was excluded because of positive expression of major and minor BCR-ABL1 transcripts in chronic myeloid leukaemia cells and the detection of minor BCR ABL1 transcripts during consolidation. Thus, 63 patients discontinued dasatinib treatment. The 25 patients who were excluded from discontinuation continued to receive dasatinib and none showed disease progression. Median follow-up was 20.0 months (IQR 16.5-24.0). Of the 63 patients who discontinued and were not excluded, 30 patients maintained deep molecular response while 33 patients had molecular relapses, all within the first 7 months after discontinuation. The estimated overall treatment-free remission was 49% (95% CI 36-61) at 6 months. No severe treatment-related toxic effects were seen. Treatment was restarted in the 33 patients with relapse; rapid molecular responses were seen in all 33 patients, of whom 29 (88%) regained deep molecular response within 3 months, as did the remaining four by 6 months. INTERPRETATION: Dasatinib discontinuation after sustained deep molecular response for more than 1 year is feasible. FUNDING: Epidemiological and Clinical Research Information Network (ECRIN). PMID- 26686408 TI - Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study. AB - BACKGROUND: Mutations in genes for perforin-dependent lymphocyte cytotoxicity are associated with haemophagocytic lymphohistiocytosis, a rare disease of severe hyperinflammation that typically becomes evident in early childhood. It has been suggested that individuals with hypomorphic biallelic mutations in genes associated with haemophagocytic lymphohistiocytosis are at increased risk of developing haematological malignancies. We aimed to assess whether relatives of patients with primary haemophagocytic lymphohistiocytosis (ie, heterozygous carriers of these mutated genes) were more likely to develop cancer. METHODS: In this retrospective cohort study, we used a multigeneration registry to identify relatives (parents and grandparents) of 79 Swedish children (<15 years) with primary haemophagocytic lymphohistiocytosis diagnosed between 1971 and 2011. For each relative, we randomly selected eight matched individuals from the Swedish total population registry, stratified for sex, birth year, and birth region. Relatives and matched controls were cross-linked with the Swedish Cancer Registry to establish cancer incidence rate. We then calculated the incidence rate ratio between first-degree and second-degree relatives and the matched controls. Additionally, we assessed natural-killer-cell-mediated cytotoxicity in a subgroup of first-degree relatives using standard 4 h (51)Cr assay and flow cytometry quantification of the upregulation of surface CD107a. FINDINGS: We identified 346 first-degree and second-degree relatives from 67 families (67 mothers, 66 fathers, 106 grandmothers, and 107 grandfathers) and 2768 matched controls. Median follow-up was 49 years, range 0-54 years. By death or last follow-up (Dec 31, 2012), first-degree relatives had a significantly increased incidence rate of malignancies than did controls (incidence rate per 1000 person-years 2.78 [95% CI 1.42-4.15] vs 1.56 [1.16-1.95]; incidence rate ratio 1.79 [95% CI 1.06-3.03]; p=0.030). Mothers had a particularly increased risk (incidence rate per 1000 person-years 4.43 [95% CI 1.99-6.87] vs 1.60 [1.08-2.11]; incidence rate ratio 2.78 [95% CI 1.48-5.21]; p=0.0014), whereas no difference was found between fathers and controls (1.24 [0.00-2.51] vs 1.52 [0.89-2.15]; 0.82 [0.29-2.29]; p=0.70) or between grandparents and controls (7.24 [5.44-9.04] vs 6.36 [5.70 7.03]; 1.14 [0.88-1.48]; p=0.33). Functional analysis of heterozygous carriers of mutations associated with haemophagocytic lymphohistiocytosis could not show significantly reduced lymphocyte cytotoxicity. INTERPRETATION: Heterozygous mutations in genes associated with haemophagocytic lymphohistiocytosis might be a new risk factor for cancer. The increased risk of cancer might imply haploinsufficiency of cytotoxic lymphocyte-mediated immunosurveillance of cancer in carriers of these mutations. Our findings might support intensified screening for malignancies in relatives of patients with haemophagocytic lymphohistiocytosis. FUNDING: Swedish Children's Cancer Foundation, Swedish Research Council, Histiocytosis Association, Swedish Cancer Society, Swedish Cancer and Allergy Foundation, Mary Beve Foundation, Karolinska Institutet Research Foundation, Stockholm County Council (ALF-project). PMID- 26686409 TI - Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis. AB - BACKGROUND: Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery. METHODS: We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30 day mortality. FINDINGS: We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232,806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0.70 (95% CI 0.49-1.02; p=0.060) for cardiac surgical trials and 1.10 (95% CI 0.96-1.27; p=0.16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2.72, 95% CI 2.11-3.49; p<0.0001) and other morbidity, although with substantial heterogeneity and small study effects. INTERPRETATION: Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery. FUNDING: None. PMID- 26686410 TI - Interview with Heribert Hirt. AB - As a son of an engineer who traveled widely during his career, Heribert Hirt began his life in the exotic country of Iran, before receiving his high-school education in Germany and then studying biochemistry at the University of Cape Town and then later at the University of Vienna, from where he received his PhD in 1987. He then worked as a postdoctoral fellow in Vienna, Oxford, and Wageningen, before starting his own group at the University of Vienna in 1993. It was also in Vienna that he became professor of genetics in 1997, followed by vice director of the Gregor Mendel Institute of Plant Molecular Biology, and later head of the Plant Molecular Biology Department of the University of Vienna. In 2007, he decided that it was time for new challenges and accepted an appointment in France to direct the Paris-based INRA-CNRS Plant Genomics Institute for the following 7 years. In 2014, Heribert embarked on yet another challenge by accepting the role to head up the Center for Desert Agriculture at King Abdullah University of Sciences and Technology (KAUST) in Saudi Arabia. PMID- 26686411 TI - Distributions of Synergistetes in clinically-healthy and diseased periodontal and peri-implant niches. AB - Bacterial taxa belonging to the phylum Synergistetes are commonly detected within diseased periodontal niches, but are rarely found within healthy oral sites. However, as they typically constitute a minor fraction of the oral microbiota, their precise distributions and disease-associations remain to be fully established. Here, we surveyed the Synergistetes taxa present within individual periodontal/subgingival and peri-implant/submucosal sites, within Chinese subjects (n = 18) affected by both peri-implantitis and periodontitis. Four individual, clinically-distinct sites were analyzed in each patient: healthy sulcus; periodontitis lesion; healthy peri-implant space; peri-implantitis lesion. We employed a clone library-based approach, using PCR-primers that specifically amplified ca. 650bp regions of the 16S rRNA gene from oral cluster A and B Synergistetes taxa. Twenty-one of the 72 sites (from 12/18 subjects) yielded Synergistetes 16S rRNA PCR products. Sequencing of cloned amplicon libraries yielded 1338 quality-filtered 16S rRNA sequences, which were assigned to 26 Synergistetes operational taxonomic units (OTUs; oral taxon SH01-SH26) using a 98.5% identity cut-off. We identified 25 Synergistetes oral cluster A OTUs (genus Fretibacterium; corresponding to Human Oral Taxon (HOT) numbers 358, 359, 360, 361, 362, 363, 452, and 453), and one oral cluster B OTU (Pyramidobacter piscolens oral taxon SH04, HOT-357). Three OTUs predominated: Fretibacterium oral taxon SH01 (HOT-360), Fretibacterium oral taxon SH02 (HOT 452), and Fretibacterium fastidiosum oral taxon SH03 (HOT-363). The Synergistetes community compositions within the respective periodontal and peri-implant sites were variable and complex, and no statistically-significant correlations could be established. However, the detection frequency of F. fastidiosum SH03 and Fretibacterium oral taxon SH01 were both positively associated with plaque index at healthy subgingival sites. Taken together, our results show that diverse Synergistetes populations inhabit both diseased and healthy periodontal and peri implant niches, with considerable site-to-site variations in composition occurring within the same oral cavity. PMID- 26686412 TI - Transcriptome profiling of human FoxP3+ regulatory T cells. AB - The major goal of this study was to perform an in depth characterization of the "gene signature" of human FoxP3(+) T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro, were analyzed via RNA sequencing (RNA seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3, IKZF2, and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes (RTKN2, LAYN, UTS2, CSF2RB, TRIB1, F5, CECAM4, CD70, ENC1 and NKG7) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs. PMID- 26686414 TI - Shear-mediated contributions to the effective properties of soft acoustic metamaterials including negative index. AB - Here we show that, for sub-wavelength particles in a fluid, viscous losses due to shear waves and their influence on neighbouring particles significantly modify the effective acoustic properties, and thereby the conditions at which negative acoustic refraction occurs. Building upon earlier single particle scattering work, we adopt a multiple scattering approach to derive the effective properties (density, bulk modulus, wavenumber). We show,through theoretical prediction, the implications for the design of "soft" (ultrasonic) metamaterials based on locally resonant sub-wavelength porous rubber particles, through selection of particle size and concentration, and demonstrate tunability of the negative speed zones by modifying the viscosity of the suspending medium. For these lossy materials with complex effective properties, we confirm the use of phase angles to define the backward propagation condition in preference to "single-" and "double-negative" designations. PMID- 26686413 TI - Transmissible Tumors: Breaking the Cancer Paradigm. AB - Transmissible tumors are those that have transcended the bounds of their incipient hosts by evolving the ability to infect another individual through direct transfer of cancer cells, thus becoming parasitic cancer clones. Coitus, biting, and scratching are transfer mechanisms for the two primary species studied, the domestic dog (Canis lupus familiaris) and the Tasmanian devil (Sarcophilus harrisii). Canine transmissible venereal tumors (CTVT) are likely thousands of years old, and have successfully travelled from host to host around the world, while the Tasmanian devil facial tumor disease (DFTD) is much younger and geographically localized. The dog tumor is not necessarily lethal, while the devil tumor has driven the population to near extinction. Transmissible tumors are uniform in that they have complex immunologic profiles, which allow them to escape immune detection by their hosts, sometimes for long periods of time. In this review, we explore how transmissible tumors in CTVT, DFTD, and as well as the soft-shell clam and Syrian hamster, can advance studies of tumor biology. PMID- 26686415 TI - Surveillance of surgical site infection after cesarean section and time of notification. AB - BACKGROUND: Cesarean section is a surgical procedure the main complication of which is surgical site infection (SSI), which is related to maternal morbidity and mortality. OBJECTIVE: To evaluate active monitoring by telephone to identify infection and time of SSI report in postpartum women and associated risk factors. METHODS: We conducted a prospective observational study from 2013-2014, at a referral service for high-risk pregnancies. Surveillance was conducted via telephone at least 30 days after cesarean delivery. Incidence ratio and time of infection occurrence (days) was analyzed. Survival analysis was conducted to assess the temporal distribution of the development of infection. RESULTS: Of a total of 353 patients, 14 (4%) cases of SSI were reported, and 10 (7.4%) of the reported cases occurred within 15 days after cesarean and average time of infection was12.21 days. American Society of Anesthesiologists score was the only risk factor associated with SSI after cesarean section. CONCLUSIONS: The prevalence of SSI after cesarean section via telephone is similar to several services with different methods of surveillance, considering it could be used by services with limited resources. Superficial incisional SSI was the most common type of infection, time of infection report was mainly before the 15th day postprocedure, and American Society of Anesthesiologists score of 2 or less was protective against SSI. Telephone calls can be a viable method to identify women with infection briefly after discharge, particularly at-risk patients. PMID- 26686416 TI - Macrophage depletion and TNF-alpha inhibition prevent resorption in CBA/J * DBA/2 model of CpG-induced abortion. AB - OBJECTIVE: To elucidate the mechanism by which embryo-resorption was enhanced by pathogenic CpG ODN motif in abortion-prone CBA/J * DBA/2 model and to develop a counter strategy for normal pregnancy outcome. METHODS: This is an animal model based study. Abortion-prone model is established by CBA/J * DBA/2. An infection was mimicked by CpG ODN injection. RESULTS: Embryo-resorption was readily induced by CpG ODN in low doses of CpG ODN (~25 MUg/dam) when intraperitoneally (IP) injected on gestational day(gd) 6.5 in male DBA/2 mated CBA/J female mice. A more modest decline in Progesterone(P4), but not Estrogen(E2) was observed after exposure to CpG ODN in the model. P4 supplement fail to improve pregnancy outcomes, even at pharmocology dose. CpG ODN-induced fetal resorption is prevented by the treatment of anti-F4/80 or by that of anti-TNFalpha.In the implantation sites, the treatment of anti-F4/80 inhibits the increase both of F4/80(+) macrophage proportion and TNF-alphaexpression level which are induced by CpG ODN. The anti-TNFalphatreatment also recovers CpG ODN-induced reduction of CD4(+)Foxp3(+) T cells. CONCLUSION: Circulating P4 is not responsible for the process by which CpG ODN-induced embryonic resorption in an abortion-prone mice. Macrophage depletion and TNF-alpha inhibition are really noteworthy for CpG ODN induced pregnancy disruption. PMID- 26686417 TI - The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration. AB - It is well-known that one of the most important features of intervertebral disc degeneration (IDD) is the extracellular matrix (ECM) degradation. Collagen and aggrecan are major components of ECM; the degradation of ECM in intervertebral discs (IVDs) is closely related to the activities of collagenase and aggrecanase. TIMP-3 is the most efficient inhibitor of aggrecanase in IVD. However, only few studies focus on the potential relationship between TIMP-3 and IDD. In our study, we found TIMP-3 gene expression was decreased after stimulating with LPS in rat nucleus pulposus (NP) cells. Then we used a lentivirus vector to reconstruct rat NP cells which high expressed TIMP-3 gene (LV-TIMP3). The upregulation of MMPs and ADAMTSs induced by LPS was significantly inhibited in LV-TIMP3 cells. After overexpression of TIMP-3, the aggrecan breakdown caused by LPS was also reduced in both monolayer culture and three-dimension culture model. To further study the relation between TIMP-3 and IDD, we collected human NP tissue samples of different degenerative degrees. Real-time PCR and immunohistochemical staining showed that the expression of TIMP-3 was negatively correlated with the degree of intervertebral disc degeneration, while MMP-1 and ADAMTS-4 were markedly increased in degenerative IVD. Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD. PMID- 26686418 TI - Low-concentration of perifosine surprisingly protects cardiomyocytes from oxygen glucose deprivation. AB - Here we found that low-concentration of perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re oxygenation. In H9c2 cardiomyocytes, non-cytotoxic perifosine (0.1-0.5 MUM) suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D complexation, as well as mitochondrial membrane potential (MMP) reduction. Molecularly, perifosine activated AMP-activated kinase (AMPK) signaling to increase intracellular NADPH (nicotinamide adenine dinucleotide phosphate) content in H9c2 cells. On the other hand, AMPK inhibition by AMPKalpha1 shRNA-knockdown in H9c2 cells significantly reduced perifosine-induced NADPH production, and alleviated perifosine-mediated anti-oxidant and cytoprotective activities against OGD/re-oxygenation. In primary murine cardiomyocytes, perifosine similarly activated AMPK signaling, and offered significant protection against OGD/re-oxygenation, which was largely attenuated with siRNA knockdown of AMPKalpha1. We demonstrate an unexpected function of perifosine (low-concentration) in protecting cardiomyocytes from OGD/re oxygenation. PMID- 26686419 TI - Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence. AB - The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-beta-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-beta-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. PMID- 26686420 TI - Morphological characterization of adult mouse Leydig cells in culture. AB - The morphology and function of Leydig cells are changed during the development, mature and senility of Leydig cells along the life span of males. This study was to observe the growth morphology of adult mouse Leydig cells in culture, aiming to provide a reference for furthermore understanding of the biological function of Leydig cells by in vitro model. Testes of two-month-old mice were decapsulated and then the Leydig cells were isolated by collagenase digestion and were cultured in DMEM/F12 supplemented with 10% FBS. The Leydig cells were identified by HSD3B staining and RT-PCR. After 48-h Leydig cell culture, both the nucleus and the cytoplasm were very clear under the optical microscope. The nucleus was big and round and the cytoplasm was filled with abundant lipid drops with a strong refractivity. After 5-day culture, Leydig cells were fully elongated in spindle, triangular, polygonal, oval or irregular shapes. Some cells grew in aggregation, and some cells grew independently. Leydig cells in aggregation elongated many cellular tentacles for intercellular connections, which formed an epithelium-like appearance. After HSD3B staining, the individual Leydig cells were stained with different extents, demonstrated that the heterogeneity of HSD3B activity in individual Leydig cells in primary culture. RT-PCR results showed that Leydig cells in culture after 5 days could express Leydig cell-specific transcriptions, HSD3B6, CYP17A1 and StAR. These results showed the morphological characterization of adult mouse Leydig cells in culture, which will lay a foundation to elucidate the relationship between the morphology and function of Leydig cells. PMID- 26686421 TI - Overexpression of the pleiotropic regulator CodY decreases sporulation, attachment and pellicle formation in Bacillus anthracis. AB - CodY, a global transcriptional regulator, primarily functions as a nutrient and energy sensor. It is activated by metabolic effectors like BCAA and GTP. In low G + C Gram positive bacteria, it facilitates coupling of changes in the cellular metabolite pool with those required in the transcriptome of the cell. This pleiotropic regulator controls the expression of a vast number of genes as the cell transits from exponential to the stationary phase. Earlier studies have shown that CodY is required for the virulence of Bacillus anthracis. We sought to investigate the effect of its overexpression on the physiology of B. anthracis. In our study, we found that cellular CodY levels were unchanged during this phase transition. Expression of endogenous CodY remained the same in different nutrient limiting conditions. Immunoblotting studies revealed CodY presence in the whole spore lysate of B. anthracis indicating it to be a component of the spore proteome. We could also detect CodY in the secretome of B. anthracis. Further, CodY was overexpressed in B. anthracis Sterne strain and this led to a 100-fold decrease in the sporulation titer and a 2.5-fold decrease in the in vitro attachment ability of the bacteria. We also observed a decrease in the pellicle formation by CodY overexpressed strain when compared to wildtype bacilli. The CodY overexpressed strain showed chaining phenotype during growth in liquid media and pellicle. PMID- 26686422 TI - Long-Term Changes in Aortic Length after Thoracic Endovascular Aortic Repair. AB - PURPOSE: To study long-term changes to the thoracic aorta following thoracic endovascular aortic repair (TEVAR) for treatment of different aortic pathologic conditions. MATERIALS AND METHODS: This retrospective study included 53 consecutive patients (mean age, 58.8 y +/- 14; 13 female and 40 male) in whom TEVAR was performed between October 2002 and May 2010. The mean duration of follow-up was 21.1 months (range, 0.5-96 mo). Statistical analysis was performed with the Friedman test and Conover-Iman test. RESULTS: Nineteen patients with aortic aneurysm (group 1), 25 patients with type B dissection (group 2), and 9 patients with other pathologic conditions (group 3) were treated with TEVAR. The mean overall aortic lengths (from the origin of the left subclavian artery to the origin of the celiac trunk) before TEVAR were 271.4 mm, 268.6 mm, and 233.6 mm in groups 1, 2, and 3, respectively. At 12-month follow-up, the lengths were 282.8 mm, 294.4 mm, and 237.5 mm in groups 1, 2, and 3, respectively. The changes in aortic lengths following TEVAR were statistically significant (P < .001). A second intervention was required in 14 patients, and 6 patients died during follow-up. CONCLUSIONS: A significant change in the overall aortic length was observed following TEVAR. The changes in aortic length reached statistical significance after 12 months. PMID- 26686423 TI - Network-assisted analysis of primary Sjogren's syndrome GWAS data in Han Chinese. AB - Primary Sjogren's syndrome (pSS) is a complex autoimmune disorder. So far, genetic research in pSS has lagged far behind and the underlying biological mechanism is unclear. Further exploring existing genome-wide association study (GWAS) data is urgently expected to uncover disease-related gene combination patterns. Herein, we conducted a network-based analysis by integrating pSS GWAS in Han Chinese with a protein-protein interactions network to identify pSS candidate genes. After module detection and evaluation, 8 dense modules covering 40 genes were obtained for further functional annotation. Additional 31 MHC genes with significant gene-level P-values (sigMHC-gene) were also remained. The combined module genes and sigMHC-genes, a total of 71 genes, were denoted as pSS candidate genes. Of these pSS candidates, 14 genes had been reported to be associated with any of pSS, RA, and SLE, including STAT4, GTF2I, HLA-DPB1, HLA DRB1, PTTG1, HLA-DQB1, MBL2, TAP2, CFLAR, NFKBIE, HLA-DRA, APOM, HLA-DQA2 and NOTCH4. This is the first report of the network-assisted analysis for pSS GWAS data to explore combined gene patterns associated with pSS. Our study suggests that network-assisted analysis is a useful approach to gaining further insights into the biology of associated genes and providing important clues for future research into pSS etiology. PMID- 26686424 TI - First Observation of Physically Capturing and Maneuvering Bacteria using Magnetic Clays. AB - A new class of nanohybrids composed of structurally exfoliated silicate platelets and magnetic iron oxide nanoparticles was synthesized and shown to be capable of capturing microbes in liquid microbiological media. Nanoscale silicate platelets with an approximate thickness of 1.0 nm were prepared from the naturally occurring mineral clays montmorillonite and mica; these clays yielded platelets with lateral dimensions on the order of 80-100 nm and 300-1000 nm, respectively. The magnetic Fe3O4 nanoparticles, approximately 8.3 nm in diameter, were coated in situ onto the silicates during the synthesis process, which involved the coprecipitation of aqueous Fe(2+)/Fe(3+) salts. Owing to the high surface area-to volume ratios and the presence of ionically charged groups (i.e., =SiO(-)Na(+)), the silicate nanoplatelets exhibited intense noncovalent bonding forces between Fe3O4 nanoparticles and the surrounding microorganisms. The Fe3O4-on-nanoplatelet nanohybrids enabled the entrapment of bacterial cells in liquid microbiological media. These captured bacteria formed bacterial aggregates on the order of micrometers that became physically maneuverable under a magnetic field. This phenomenon was demonstrated with Staphylococcus aureus in liquid microbiological media by physically removing them using a magnetic bar; in two experimental examples, bacterial concentrations were reduced from 10(6) to 10(2) and from 10(4) to 10(0) CFU/mL (colony formation unit/mL con). Under a scanning electron microscope, these bacteria appeared to have rough and wrinkled surfaces due to the accumulated silicate platelets. Furthermore, the external application of a high-frequency magnetic field completely destroyed these aggregated microbes by the magnetically induced heat. Hence, the newly developed nanohybrids were shown to be viable for physically capturing microbes and also for potential hyperthermia treatment applications. PMID- 26686426 TI - Complications following orthognathic surgery for patients with cleft lip/palate: A systematic review. AB - BACKGROUND/PURPOSE: The purpose of this systematic review is to update the available data for complications following orthognathic surgery in cleft lip and/or palate patients. METHODS: Three electronic databases (Medline, Embase, and Cochrane) were searched for publications from 1990 to 2014. RESULTS: A total of 26 articles were selected including 1003 patients (male: 391, female: 353, 259: not mentioned) who underwent maxillary osteotomies for cleft lip/palate. Mean age at surgery was 19.3 years (range: 8.5-60 years). Overall perioperative complications were reported in 126 cases (12.76%). The most common complication was closure failure of pre-existing palatal fistula (28.57%), followed by velopharyngeal impairment (16.79%), closure failure of pre-existing alveolar fistula (10.74%), gingival recession (4.55%), and failure of premaxilla stabilization in bilateral cases (4.55%). Severe vascular complications included one arteriovenous fistula (0.10%), one maxillary aneurysm (0.10%), and one cavernous sinus thrombosis (0.10%). Mean horizontal relapse rate was 17.9% (range: -20.0% to 37.2%), and mean vertical relapse rate was 35.4% (range: -25.9% to 162.5%). Reoperation rate was 12.2% (range: 0.0-64.0%). Prospective studies or randomized trials were rare. CONCLUSION: To obtain a dataset with higher evidence, a prospective multicenter study should be conducted with clearly defined criteria for each complication. PMID- 26686428 TI - It is Worth it to Increase the Use of Extracorporeal Membrane Oxygenation? PMID- 26686427 TI - Trends in U.S. Extracorporeal Membrane Oxygenation Use and Outcomes: 2002-2012. AB - This study evaluates contemporary trends in the use and outcomes of adult patients undergoing extracorporeal membrane oxygenation (ECMO) in U.S. hospitals. All adult discharges in the Nationwide Inpatient Sample database during the years 2002-2012 that included ECMO were used to estimate the total number of U.S. ECMO hospitalizations (n = 12,407). Diagnostic codes were used to group patients by indication for ECMO use into postcardiotomy, heart transplant, lung transplant, cardiogenic shock, respiratory failure, and cardiopulmonary failure. A Mann Kendall test was used to examine trends over time using standard statistical techniques for survey data. We found that ECMO use increased significantly from 2002-2012 (P = 0.003), whereas in-hospital mortality rate fluctuated without a significant difference in trend over time. No significant trend was observed in overall ECMO use from 2002-2007, but the use did demonstrate a statistically significant increase from 2007-2012 (P = 0.0028). The highest in-hospital mortality rates were found in the postcardiotomy (57.2%) and respiratory failure (59.2%) groups. Lung and heart transplant groups had the lowest in-hospital mortality rates (44.10% and 45.31%, respectively). The proportion of ECMO use for postcardiotomy decreased from 56.9% in 2002 to 37.9% in 2012 (P = 0.026) and increased for cardiopulmonary failure from 3.9% to 11.1% (P = 0.026). We concluded that ECMO use in the United States increased between 2002 and 2012, driven primarily by increase in national ECMO use beginning in 2007. Mortality rates remained high but stable during this time period. Though there were shifts in relative ECMO use among patient groups, absolute ECMO use increased for all indications over the study period. PMID- 26686429 TI - Posterior Leaflet Detachment, Augmentation, and Reconstruction for Treatment of Functional Mitral Valve Regurgitation. AB - Functional mitral regurgitation caused posterior leaflet tethering and central malcoaptation treated utilizing undersized annuloplasty alone is associated with high rates of early failure. We report the technical steps necessary for near complete near complete detachment, augmentation and reconstruction of a thin and diminutive posterior mitral leaflet to reproducibly re-establish normal mitral leaflet coaptation and eliminate functional MR. PMID- 26686430 TI - Patch Augmentation of Mitral Valve Leaflet in Ischemic Mitral Regurgitation. PMID- 26686425 TI - Delivery of cancer therapeutics to extracellular and intracellular targets: Determinants, barriers, challenges and opportunities. AB - Advances in molecular medicine have led to identification of worthy cellular and molecular targets located in extracellular and intracellular compartments. Effectiveness of cancer therapeutics is limited in part by inadequate delivery and transport in tumor interstitium. Parts I and II of this report give an overview on the kinetic processes in delivering therapeutics to their intended targets, the transport barriers in tumor microenvironment and extracellular matrix (TME/ECM), and the experimental approaches to overcome such barriers. Part III discusses new concepts and findings concerning nanoparticle-biocorona complex, including the effects of TME/ECM. Part IV outlines the challenges in animal-to-human translation of cancer nanotherapeutics. Part V provides an overview of the background, current status, and the roles of TME/ECM in immune checkpoint inhibition therapy, the newest cancer treatment modality. Part VI outlines the development and use of multiscale computational modeling to capture the unavoidable tumor heterogeneities, the multiple nonlinear kinetic processes including interstitial and transvascular transport and interactions between cancer therapeutics and TME/ECM, in order to predict the in vivo tumor spatiokinetics of a therapeutic based on experimental in vitro biointerfacial interaction data. Part VII provides perspectives on translational research using quantitative systems pharmacology approaches. PMID- 26686431 TI - Elevated Stroke Risk Associated With Femoral Artery Cannulation During Mitral Valve Surgery. AB - Minimally invasive mitral valve (MV) surgery, often requiring femoral artery (FA) cannulation, is increasingly being adopted. There is concern about increased stroke rates associated with minimally invasive MV surgery. This study aims to examine whether FA cannulation is independently associated with increased stroke rates in minimally invasive MV procedures. MV procedures from January 2004 to June 2012 were reviewed using our institutional Society of Thoracic Surgeons database. We included 384 patients after the exclusion of patients with emergency procedures, with infective endocarditis, who underwent other concomitant procedures, who were older than 60 years, and with nonstandard aortic clamping (endoballoon or no clamp). Patients were divided into 2 groups: those who underwent aortic cannulation (n = 327) and those who underwent femoral cannulation (n = 57). Risk adjustments through multivariable regression were used to identify independent predictors for various outcomes. Adjustments were made for cardiopulmonary bypass and aortic clamp times. Preoperatively, the femoral cannulation group had less baseline cerebrovascular disease (P = 0.032), heart failure (P = 0.028), and atrial fibrillation (P = 0.012). Other baseline characteristics were similar. The aortic cannulation group had shorter cardiopulmonary bypass (P < 0.001) and clamp times (P < 0.001). There were more repairs done in the FA cannulation group as opposed to replacements. Risk adjusted outcomes showed a higher incidence of permanent stroke in the femoral cannulation group (P = 0.032). Other outcomes were not significantly different. In conclusion, FA cannulation may be associated with increased stroke rates in isolated MV surgery. Antegrade arterial cannulation (direct aortic or axillary cannulation) may be preferable in minimally invasive MV procedures. Randomized trial data are needed. PMID- 26686432 TI - Are We Going Backwards or Forwards in Minimally Invasive Mitral Valve Surgery? Three Eras of Perfusion Strategy. PMID- 26686433 TI - Outcomes of Open Surgical Repair for Type B Dissecting Aortic Aneurysm With Alternative Methods in the Endovascular Stent Era. AB - We assessed the midterm outcomes of 2 types of open surgical repair for type B dissecting aortic aneurysm (BDA). During the last 4 years, 86 patients with BDA (mean age, 68.5 +/- 9.8 years; range: 41-87 years) underwent open repair. The average duration between the dissection onset and surgery was 51.5 +/- 31.3 months. If the BDA was of open type with patent false lumen or the aneurysm extended for a long segment, descending or thoracoabdominal aortic repair was performed with left thoracotomy. If the BDA was of the closed type with thrombosed false lumen and the aneurysm was located around the distal arch, open stent implantation was performed with our unique technique using circulatory arrest with a rectal temperature of 28 degrees C without any cerebral perfusion. Left thoracotomy was performed in 68 patients. The durations of aortic clamping and cardiopulmonary bypass were 65.2 +/- 16.9 and 78.5 +/- 34.6 minutes, respectively. Open stent implantation was performed in 18 patients. The durations of circulatory arrest and cardiopulmonary bypass were 19.1 +/- 5.1 and 86.2 +/- 17.8 minutes, respectively. In the present study, 4 patients (4.7%) required reexploration for bleeding and 1 patient (1.2%) had a stroke, but none suffered paraplegia. The hospital mortality rate was 1.2% (1 patient), resulting from retrograde type A dissection. The actuarial aortic event-free survival rate, including operative death, was 96.4% at 3 years. Both open surgical procedures for BDA were relatively safe, with favorable early and midterm outcomes, and may be superior for avoiding neurologic complications. PMID- 26686434 TI - It Is Difficult to Compare Apples to Oranges: Acute and Chronic Type B Aortic Dissections, Complicated and Uncomplicated, Are Different and Should Be Treated as Such. PMID- 26686435 TI - Micromorphology of Skeletonized and Pedicled Internal Thoracic and Radial Arteries. AB - The objective of the study was to estimate the internal thoracic arteries (ITA) and radial arteries (RA) micromorphologic features by light microscopy after harvesting them using the skeletonization and pedicled methods in patients undergoing coronary artery bypass grafting. The micromorphologic characteristics of ITA and RA were studied by luminous microscopy in 61 patients undergoing coronary artery bypass grafting. A total of 122 ITA and RA segments harvested during surgery, fixed in formalin, and stained with hematoxiline and eosin were evaluated. The mean intima-media thickness of ITA was 9.2 and 134.7 um and that of RA was 9.1 and 334.2 um, respectively. In the distal segment of ITA the media intima relation was 1.5 times bigger than in the proximal segment. None of ITA specimens contained atherosclerotic plaques or lipid inclusions. Atherosclerotic plaques were found in 3 (5%) RA specimens. Other degenerative changes were detected in 30%-74.2% of the specimens: splitting of internal elastic lamina, reduced tortuosity of the internal elastic lamina, and thickening and detachment of the intima; their incidence was associated with the skeletonization of the vessels. In conclusion, the incidence of ITA and RA degenerative changes varies from 30%-74.2% and its increase is associated with the skeletonization of the vessels, which is statistically significant. The media of the RA is 2.5 times thicker than that of the ITA (P < 0.01). This fact shows that RA has higher spasmogenic potential than that of ITA. The distal segment of the ITA has 1.5 times bigger media-intima relation than the proximal segment. Therefore, in case of enough graft length, it is recommended to avoid the distal segment and cut it off. PMID- 26686436 TI - Harvesting Arterial Grafts: Barebones or More. PMID- 26686437 TI - Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy. AB - Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P < 0.0001). In study 2, 34.99% of group A provided a heart and 20.99% provided lungs. In group B only 25.76% provided a heart and 15.09% provided lungs, an increase of 9.23% (hearts) and 5.90% (lungs), respectively, in group A (both P < 0.0001). The results of multiple regression analyses indicated a beneficial effect of T3/T4 on heart (P < 0.0001) and lung (P < 0.0001) procurement independent of other factors. T3/T4 therapy to the donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. PMID- 26686438 TI - Optimizing Donor Quality Via Hormonal Therapy: An Important Strategy to Increase Successful Placement of Thoracic Organs in End-Stage Patients. PMID- 26686439 TI - Treatment of Thoracic Aortic Aneurysm: Role of Earlier Intervention. AB - For this article, we are asked to make a case for early surgery in thoracic aortic aneurysm (TAA) disease. We are able to accumulate arguments in favor of early surgery. Specifically, (1) it is impossible to predict the onset of aortic dissection with complete accuracy. (2) Aortic dissection that is allowed to occur has high early mortality and impaired late survival. (3) Aortic surgery is very safe in the present era. (4) Living with a TAA, the inherent risk of aortic dissection has a high emotional burden. For these reasons, a case for early prophylactic surgery in TAA disease can fairly be made. PMID- 26686440 TI - The Society of Thoracic Surgeons Adult Cardiac Surgery Database: The Driving Force for Improvement in Cardiac Surgery. AB - Initiated in 1989, the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) includes more than 1085 participating centers, representing 90% 95% of current US-based adult cardiac surgery hospitals. Since its inception, the primary goal of the STS ACSD has been to use clinical data to track and improve cardiac surgical outcomes. Patients' preoperative risk characteristics, procedure related processes of care, and clinical outcomes data have been captured and analyzed, with timely risk-adjusted feedback reports to participating providers. In 2006, STS initiated an external audit process to evaluate STS ACSD completeness and accuracy. Given the extremely high inter-rater reliability and completeness rates of STS ACSD, it is widely regarded as the "gold standard" for benchmarking cardiac surgery risk-adjusted outcomes. Over time, STS ACSD has expanded its quality horizons beyond the traditional focus on isolated, risk adjusted short-term outcomes such as perioperative morbidity and mortality. New quality indicators have evolved including composite measures of key processes of care and outcomes (risk-adjusted morbidity and risk-adjusted mortality), longer term outcomes, and readmissions. Resource use and patient-reported outcomes would be added in the future. These additional metrics provide a more comprehensive perspective on quality as well as additional end points. Widespread acceptance and use of STS ACSD has led to a cultural transformation within cardiac surgery by providing nationally benchmarked data for internal quality assessment, aiding data-driven quality improvement activities, serving as the basis for a voluntary public reporting program, advancing cardiac surgery care through STS ACSD-based research, and facilitating data-driven informed consent dialogues and alternative treatment-related discussions. PMID- 26686441 TI - Selection of Valve Prostheses. AB - The lack of an ideal prosthetic heart valve leaves surgeons and their patients with a difficult choice at the time of valve replacement surgery. Current guidelines mainly emphasize patient age, contraindications to anticoagulation, and patient desires in their recommendations for the type of prosthesis to implant. Aortic valve replacement is the most frequently performed valve replacement, and 5 articles in recent years have presented important data on outcomes with different prosthesis types. The findings suggest that in young patients, transvalvular prosthesis gradients have an effect on long-term bioprosthesis durability. Use of the bioprosthesis with the best hemodynamic profile for each patient may improve prosthesis longevity and negate the advantages of mechanical valves. In older patients, the new sutureless bioprostheses appear to facilitate surgical aortic valve replacement and become an alternative to transcatheter technologies in medium- to high-risk patients. PMID- 26686442 TI - Should Tricuspid Annuloplasty be Performed With Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot? AB - Indications for prophylactic tricuspid annuloplasty in patients with pulmonary regurgitation (PR) after tetralogy of Fallot (TOF) repair are unclear and often extrapolated from acquired functional tricuspid regurgitation (TR) data in adults, where despite correction of primary left heart pathology, progressive tricuspid annular dilation is noted beyond a threshold diameter >4 cm (21 mm/m(2)). We hypothesized that unlike in adult functional TR, in pure volume overload conditions such as patients with PR after TOF, the tricuspid valve size is likely to regress after pulmonary valve replacement (PVR). A total of 43 consecutive patients who underwent PVR from 2005 until 2012 at a single institution were retrospectively reviewed. Absolute and indexed tricuspid annulus diameters (TADs), tricuspid annulus Z-scores, grade of TR along with right ventricular size, and function indices were recorded before and after PVR. Preoperative and postoperative echocardiographic data were available in all patients. A higher tricuspid valve Z-score correlated with greater TR both preoperatively (P = 0.005) and postoperatively (P = 0.02). Overall reductions in the absolute and indexed TAD and tricuspid valve Z-scores were seen postoperatively, with greater absolute as well as percentage reduction seen with larger preoperative TAD index (P = 0.007) and higher tricuspid annulus Z-scores (P = 0.06). In pure volume-overload conditions such as patients with PR after TOF, reduction in the tricuspid valve size is seen after PVR. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone. PMID- 26686443 TI - Pulmonary Insufficiency Leads to Right Ventricular Enlargement, which Leads to Tricuspid Regurgitation, which Leads to more Right Ventricular Enlargement, which Leads to more Tricuspid Regurgitation: a Vicious Cycle? PMID- 26686444 TI - Unsatisfactory Early and Late Outcomes After Fontan Surgery Delayed to Adolescence and Adulthood. AB - The ideal age to perform the Fontan procedure is still unknown. The aim of this study is to determine outcomes after Fontan surgery delayed to adolescence and adulthood in Australia and New Zealand. Patients who had undergone a Fontan procedure at 15 years of age or older were identified in the 1133 patients registered in the Australia and New Zealand Fontan Registry until December 2012. A total of 45 patients underwent the following Fontan procedure at a median age of 18.3 years (16-21 years): 24 atriopulmonary connections, 10 lateral tunnel, and 11 extracardiac conduits. Hospital mortality was 13% (6 of 45). After a mean follow-up of 15.5 +/- 9 years, there were 8 late deaths. Survival rates after 10, 20, and 25 years were 79% (95% CI: 64-89), 70% (95% CI: 51-83), and 70% (95% CI: 51-83), respectively. Freedom from Fontan failure (death, heart transplantation, Fontan takedown, protein-losing enteropathy, and poor functional status) after 10 and 20 years was 63% (95% CI: 47-76) and 35% (95% CI: 19-52), respectively. Patients with a single left ventricle had a lower risk of failure (hazard ratio = 0.25, 95% CI: 0.10-0.59; P = 0.002). Arrhythmias developed in 29 patients after a median of 0.1 years (0-9.3 years) and 10 required a permanent pacemaker. Freedom from all adverse events at 10 years was 30% (95% CI: 16-45). Outcomes of the Fontan procedure in adolescents and adults are poor, with disproportionately high hospital mortality and late adverse events. The Fontan procedure should not be delayed to adolescence and adulthood and should be performed electively in childhood. PMID- 26686445 TI - The Fontan Operation: Is Timing Everything? PMID- 26686446 TI - Management of Interrupted Aortic Arch. AB - The introduction of prostaglandin E1 in the late 1970s revolutionized the management of interrupted aortic arch. Complete resuscitation should proceed over several days if necessary before surgery is undertaken. One-stage primary neonatal repair with direct arch anastomosis and ventricular septal defect closure is the preferred surgical approach. Selective cerebral perfusion with near-infrared monitoring is being used with increasing frequency. Although repair of interrupted arch is physiologically corrective, it should not be viewed as fully corrective because of the high incidence of important late left ventricular outflow tract obstruction. This may respond to a simple surgical reintervention such as subaortic resection, but in some cases, an extensive procedure to enlarge the left ventricular outflow tract is necessary. However, procedures directed against subaortic stenosis should rarely be used as part of the initial surgical management during the neonatal period. Careful developmental follow-up is needed for all patients because of the high incidence of DiGeorge syndrome, which frequently manifests as moderately severe developmental delay. PMID- 26686447 TI - Tetralogy of Fallot. PMID- 26686448 TI - The 3-Hole Minimally Invasive Esophagectomy: A Safe Procedure Following Neoadjuvant Chemotherapy and Radiation. AB - Induction therapy followed by esophagectomy has become standard for treatment of intermediate-stage esophageal cancer in many centers. Herein we evaluate the feasibility and safety of the 3-hole minimally invasive esophagectomy (3HMIE) approach in patients who received induction radiation and chemotherapy. Between 2003 and 2012, the records of 119 consecutive patients with esophageal cancer who underwent 3HMIE were reviewed for perioperative complications and long-term outcomes. Comparison was made between procedures performed for patients receiving neoadjuvant chemoradiation and patients who were treated with only surgery. Of them, 78 patients received neoadjuvant chemoradiation and 41 patients were treated with only surgery. Tumor locations were upper (2), middle (16), distal (64), and gastroesophageal junction (37). In all, 76 patients were at clinical stage IIA or above at presentation. Increased requirement for blood replacement in the induction therapy group was significant compared with the surgery-only group. Operative time, estimated blood loss, proximal and distal margin lengths, and length of stay were not significantly different between the cohorts. There was a 30-day perioperative death (0.8%), and this patient was from the surgery only group. No conduit necrosis or need for diversion was recorded. Overall, 5 year survival was 62% among the 107 patients with early-stage esophageal cancer. 3HMIE is feasible with low mortality and acceptable morbidity even in patients with locally advanced esophageal cancer who received neoadjuvant radiochemotherapy. Overall perioperative and survival outcomes are similar to or better than those reported in the published literature on esophagectomy after induction therapy. PMID- 26686449 TI - With Minimally Invasive Esophagectomy, Thoracic Surgeons Must Avoid Falling into the Same Trap Again! PMID- 26686450 TI - Endobronchial Treatment of Bronchopleural Fistulas by Using Intrabronchial Valve System: A Case Series. AB - Air leaks, alveolopleural or bronchopleural fistulas, either spontaneous, iatrogenic, or postsurgical, can be difficult to treat, and if prolonged in spite of proper chest tube thoracostomy they may require surgical or chemical pleurodesis with variable success. Intrabronchial valve (IBV) treatment is minimally invasive and has a potential to shorten the duration of air leaks in well-selected patients with ongoing air leaks. The study included 19 patients with prolonged air leaks treated with IBVs spiration, with a total of 71 valves placed at a tertiary university hospital. Internal Board Review approval was obtained to use IBVs for off-label indication. IBVs were placed in desired airways with 100% accuracy in patients with air leaks without complications, including self-migration. All 19 patients with air leaks were initially treated with chest tube thoracostomy and in addition chemical pleurodesis in 2 and blood patch in a patient without success. After IBV placement, all patients but one with air leak had successful resolution of the air leak and removal of chest tube in a median of 3 days (range: 2-45 days). In conclusion, the use of IBVs for prolonged air leaks in various etiologies is effective and safe. PMID- 26686451 TI - One-Way Valves to the Rescue for Bronchopleural Fistulae. PMID- 26686452 TI - Maximal Oxygen Uptake--Risk Predictor of NSCLC Resection in Patients With Comorbid Emphysema: Lessons From NETT. AB - We compared VO2 max values from ACCP Guidelines and from NETT's homogenous NULPD surrogate for predicting operative mortalities. Estimated mid and long-term non cancer related survival in NETT's subset was also obtained. NETT and ACCP Guideline VO2 max values were similar in the "low" and "mid" risk operative mortality categories but NETT's "high" risk subset showed lower mortality (14% vs. 26%). Estimated non-cancer related survival in NETT "low", "mid" and "high" risk VO2 max categories at two and eight years were 100%, 74%, 59% and 48%, 26%, 14%, respectively. The lower predicted risk in NETT's "high- risk" subset raises the possibility of extending indications for potential curative resection in selected patients. The NETT surrogate also provides hitherto unavailable estimate on long-term non-cancer related survival after potential curative resection of NSCLC and suggests that the operation does not shorten eight-year longevity. PMID- 26686453 TI - How Can The National Emphysema Treatment Trial Provide Guidance In Risk Stratification For Patients With Severe Emphysema And Early Stage Nonsmall Cell Lung Cancer. PMID- 26686454 TI - Recent and Future Developments in Chest Wall Reconstruction. AB - Reconstruction following major chest wall resection can be challenging. Conventional methods of using mesh with or without incorporation of methyl methacrylate are slowly being replaced by chest wall reconstruction prosthetic systems that use titanium plates or bars. The most popular systems in use are the titanium STRATOS bars and MatrixRIB plates, which have different systems for securing to the chest wall. In general, these new approaches are user friendly, are more ergonomic, and may avoid certain complications associated with the more conventional methods of reconstruction. However, the successful implantation of these titanium prosthetic systems requires the operator to be familiar with the limitations and potential pitfalls of the process. Follow-up data are only just emerging on the risk factors for implant failure of these prosthetic systems, as well as certain device-specific complications, with fracture failure being increasingly recognized as a significant problem. In the future, emerging intraoperative real-time imaging and 3-dimensional printing technology, as well as development in biomaterials, will allow chest wall reconstruction to become increasingly personalized. PMID- 26686455 TI - Induction Therapy for Mesothelioma. AB - One particular approach of multimodality treatment for mesothelioma is induction therapy followed by surgery. Among its several advantages, the most important is downstaging of the tumor into a resectable stage, although morbidity and mortality might be increased. In this article we review the principles and outcome of different modalities for induction treatment of mesothelioma. PMID- 26686456 TI - What the Surgeon Needs to Know About Databases. AB - Data collection is one of the most important instruments of any quality improvement initiatives. We have selected, summarized, and discussed 5 recent contributions mostly based on large international databases, which we considered most relevant to our specialty. They focused on different aspects: the selection and rigorous definition of the variables contained in the data set, the evaluation of a treatment or a pathway of care by the analysis of the observed outcomes, the identification of risk factors able to affect the surgical course, the measurement of the quality provided by a care giver, and the assessment of the quality of the data collected and the planning of quality improvement activities. PMID- 26686457 TI - Circular dichroism based refractive index sensing using chiral metamaterials. AB - A new strategy to improve the sensing ability of localized surface plasmon resonance sensors is presented. By employing chiral plasmonic nanostructures, circularly polarized differential transmittance can show enhanced sensing performance over circularly polarized transmittance under certain conditions. PMID- 26686458 TI - A multi-mode operation control strategy for flexible microgrid based on sliding mode direct voltage and hierarchical controls. AB - Multi-mode operation and transient stability are two problems that significantly affect flexible microgrid (MG). This paper proposes a multi-mode operation control strategy for flexible MG based on a three-layer hierarchical structure. The proposed structure is composed of autonomous, cooperative, and scheduling controllers. Autonomous controller is utilized to control the performance of the single micro-source inverter. An adaptive sliding-mode direct voltage loop and an improved droop power loop based on virtual negative impedance are presented respectively to enhance the system disturbance-rejection performance and the power sharing accuracy. Cooperative controller, which is composed of secondary voltage/frequency control and phase synchronization control, is designed to eliminate the voltage/frequency deviations produced by the autonomous controller and prepare for grid connection. Scheduling controller manages the power flow between the MG and the grid. The MG with the improved hierarchical control scheme can achieve seamless transitions from islanded to grid-connected mode and have a good transient performance. In addition the presented work can also optimize the power quality issues and improve the load power sharing accuracy between parallel VSIs. Finally, the transient performance and effectiveness of the proposed control scheme are evaluated by theoretical analysis and simulation results. PMID- 26686460 TI - Global DNA methylation and related mRNA profiles in sheep oocytes and early embryos derived from pre-pubertal and adult donors. AB - The developmental capacity of in vitro-matured oocytes and in vitro-fertilized embryos from pre-pubertal sheep is less than that of adult counterparts, and epigenetic mechanisms are thought to be involved. In the present study, germinal vesicle stage oocytes were collected by follicular aspiration from superovulated 4-week-old lambs and 2.5-year-old ewes. There were evaluations of the developmental potential of oocytes and embryos by in vitro culture and fertilization, global DNA methylation and hydroxymethylation patterns by immunofluorescence staining, and relative abundance of enzyme mRNA by quantitative real-time polymerase chain reaction analysis in pre-pubertal and adult sheep donors. The results showed that the rates of maturation and cleavage of oocytes as well as pregnancy and lambing rates from the transfer of 2-cell embryos collected from lambs were less than those from adults (P<0.05). The global DNA methylation and hydroxymethylation and relative abundance of Dnmt1, Dnmt3a, and Tet3 mRNA were less at all stages of oocytes, zygotes, and two-cell embryos from lambs compared with those from adults (P<0.05) with no difference in relative abundance of Dnmt3b mRNA. Thus, younger donor age was associated with disturbed DNA methylation processes due to insufficient methyltransferases during gametogenesis and early embryonic development, and this may be responsible for the lesser developmental potential of oocytes and early developing embryos when oocytes are collected from lambs. PMID- 26686459 TI - The Roles of MicroRNA-122 Overexpression in Inhibiting Proliferation and Invasion and Stimulating Apoptosis of Human Cholangiocarcinoma Cells. AB - Our study investigated whether microRNA-122 (miR-122) played important roles in the proliferation, invasion and apoptosis of human cholangiocarcinoma (CC) cells. QBC939 and RBE cells lines were chosen and divided into five groups: miR-122 mimic group, anti-miR-122 group, negative control (NC) group, mock group and blank group. MiR-122 expression was measured by qRT-PCR. Roles of miR-122 in cell proliferation, apoptosis and invasion were investigated using MTT assay, flow cytometer and Transwell invasion assay, respectively. MiR-122 expression was lower in CC tissues and QBC939 cell than that in normal bile duct tissues, HCCC 9810 and RBE cells. In both QBC939 and RBE cells lines, miR-122 expression was higher in miR-122 mimic group than that in NC group, mock group and blank group; opposite results were found in anti-miR-122 group. Cell proliferation and invasion were remarkably inhibited in miR-122 mimic group after 48 h/72 h transfection, while apoptotic cells numbers were much greater in miR-122 mimic group; the opposite results were obtained from anti-miR-122 group (all P < 0.05). MiR-122 expression was significantly weaker in CC tissues, and miR-122 overexpression might play pivotal roles in inhibiting proliferation, stimulating apoptosis and suppressing invasion of CC cells, suggesting a new target for CC diagnosis and treatment. PMID- 26686461 TI - Correlation of bone marrow abnormalities, peripheral lymphocyte subsets and clinical features in uncomplicated common variable immunodeficiency (CVID) patients. AB - B cell developmental defects in CVID were recently described in a limited number of cases. To date, a detailed correlation between this maturational defect and the clinical presentation of affected patients has not been reported. In this study, we correlated bone marrow B cell evaluation, peripheral B and T lymphocyte subsets and clinical findings in 15 CVID patients. Early B cell developmental defects were observed in one third of patients. Combined bone marrow and peripheral lymphocytes evaluation allowed to further subdivide CVID patients in three groups with shared clinical features at diagnosis and during follow-up. These data broaden the number of CVID patients with early B cell developmental defects and, together with the peripheral lymphocytes evaluation, offer insight into the related clinical features in affected patients. PMID- 26686462 TI - Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: Implications for a therapeutic design. AB - We characterised the expression of semaphorin (sema)3A, sema7A and their receptors in the immune and the central nervous system (CNS) at different stages of experimental autoimmune encephalomyelitis (EAE). We also studied their expression in neonatal and adult oligodendrocyte progenitor cell (OPC) and in mature oligodendrocyte cultures. Our results show that sema3A is increased in the CNS and decreased in the immune system upon EAE induction. However, sema7A expression is increased in both the CNS and the immune system during EAE. We also detected sema3A, sema7A and their receptors in neonatal and adult OPCs and in mature oligodendrocytes. These data suggest that sema3A and sema7A are involved in the pathogenesis of EAE, in the modulation of the immune response and in the neurodegeneration that take place in the CNS. Sema7A may represent an intriguing potential therapeutic target for the treatment of both the neurodegenerative and immune-mediated disease processes in MS. PMID- 26686463 TI - Effects of short-term hyper- and hypo-osmotic exposure on the osmoregulatory strategy of unfed North Pacific spiny dogfish (Squalus suckleyi). AB - The North Pacific spiny dogfish (Squalus suckleyi) is a partially euryhaline species of elasmobranch that often enter estuaries where they experience relatively large fluctuations in environmental salinity that can affect plasma osmolality. Previous studies have investigated the effects of altered salinity on elasmobranchs over the long term, but fewer studies have conducted time courses to investigate how rapidly they can adapt to such changes. In this study, we exposed unfed (no exogenous source of nitrogen or TMAO) spiny dogfish to hyper- and hypo-osmotic conditions and measured plasma and tissue osmolytes, nitrogen excretion, and changes in enzyme activity and mRNA levels in the rectal gland over 24h. It was shown that plasma osmolality changes to approximately match the ambient seawater within 18-24h. In the hypersaline environment, significant increases in urea, sodium, and chloride were observed, whereas in the hyposaline environment, only significant decreases in TMAO and sodium were observed. Both urea and ammonia excretion increased at low salinities suggesting a reduction in urea retention and possibly urea production. qPCR and enzyme activity data for Na(+)/K(+)-ATPase did not support the idea of rectal gland activation following exposure to increased salinities. Therefore, we suggest that the rectal gland may not be a quantitatively important aspect of the dogfish osmoregulatory strategy during changes in environmental salinity, or it may be active only in the very early stages (i.e., less than 6h) of responses to altered salinity. PMID- 26686464 TI - Foreword for the special issue on the ninth international workshop on low energy electron microscopy and photoemission electron microscopy. PMID- 26686467 TI - Practitioner Review: Involving young people with callous unemotional traits in treatment--does it work? A systematic review. AB - BACKGROUND: Children and adolescents with callous unemotional (CU) traits are at risk of severe and persistent antisocial behavior. It is commonly assumed that these children are difficult to treat but it has been proposed that they may benefit from being involved in interventions that go beyond typical parent training programs. This systematic review sought to answer two previously unanswered questions: do interventions involving young people reduce levels of CU traits? Do CU traits predict the effectiveness of interventions for antisocial behavior involving young people? METHOD: Studies were included that adopted an randomized controlled trial, controlled or open trial design and that had examined whether treatment was related to reductions in CU traits or whether CU traits predicted or moderated treatment effectiveness. RESULTS: Treatments used a range of approaches, including behavioral therapy, emotion recognition training, and multimodal interventions. 4/7 studies reported reductions in CU traits following treatment. There was a mixed pattern of findings in 15 studies that examined whether CU traits predicted treatment outcomes following interventions for antisocial behavior. In 7/15 studies, CU traits were associated with worse outcomes, although three of these studies did not provide data on baseline antisocial behavior, making it difficult to evaluate whether children with high CU traits had shown improvements relative to their own behavioral baseline, despite having the worst behavioral outcomes overall. CU traits did not predict outcomes in 7/15 studies. Finally, a single study reported that CU traits predicted an overall increased response to treatment. CONCLUSIONS: Overall, the evidence supports the idea that children with CU traits do show reductions in both their CU traits and their antisocial behavior, but typically begin treatment with poorer premorbid functioning and can still end with higher levels of antisocial behavior. However, there is considerable scope to build on the current evidence base. PMID- 26686465 TI - 3D Chromosome Regulatory Landscape of Human Pluripotent Cells. AB - In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease. PMID- 26686468 TI - Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase. AB - Peroxiredoxin-3 (Prx3) accounts for about 90% of mitochondrial peroxidase activity, and its marked upregulation in many cancers is important for cell survival. Prx3 oxidation can critically alter peroxide signaling and defense and can be a seminal event in promoting cell death. Here it is shown that this mechanism can be exploited pharmacologically by combinations of clinically available drugs that compromise Prx3 function in different ways. Clinically relevant levels of the thiosemicarbazone iron chelators triapine (Tp) and 2,2' Dipyridyl-N,N-dimethylsemicarbazone (Dp44mT) promote selective oxidation of mitochondrial Prx3, but not cytosolic Prx1, in multiple human lung and ovarian cancer lines. Decreased cell survival closely correlates with Prx3 oxidation. However, Prx3 oxidation is not merely an indicator of cell death as cytotoxic concentrations of cisplatin do not cause Prx3 oxidation. The siRNA-mediated suppression of either Prx3 or thioredoxin-2, which supports Prx3, enhances Tp's cytotoxicity. Tp-mediated Prx3 oxidation is driven by enhanced peroxide generation, but not by nitric oxide. Many tumors overexpress thioredoxin reductase (TrxR) which supports Prx activity. Direct inhibitors of TrxR (e.g. auranofin, cisplatin) markedly enhanced Tp's cytotoxicity, and auranofin enhanced Prx3 oxidation by low dose Tp. Together, these results support an important role for Prx3 oxidation in the cytotoxicity of Tp, and demonstrate that TrxR inhibitors can significantly enhance Tp's cytotoxicity. Thiosemicarbazone-based regimens could prove effective for targeting Prx3 in a variety of cancers. PMID- 26686466 TI - Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration. AB - How resident stem cells and their immediate progenitors rebuild tissues of pre injury organization and size for proportional regeneration is not well understood. Using 3D, time-lapse intravital imaging for direct visualization of the muscle regeneration process in live mice, we report that extracellular matrix remnants from injured skeletal muscle fibers, "ghost fibers," govern muscle stem/progenitor cell behaviors during proportional regeneration. Stem cells were immobile and quiescent without injury whereas their activated progenitors migrated and divided after injury. Unexpectedly, divisions and migration were primarily bi-directionally oriented along the ghost fiber longitudinal axis, allowing for spreading of progenitors throughout ghost fibers. Re-orienting ghost fibers impacted myogenic progenitors' migratory paths and division planes, causing disorganization of regenerated muscle fibers. We conclude that ghost fibers are autonomous, architectural units necessary for proportional regeneration after tissue injury. This finding reinforces the need to fabricate bioengineered matrices that mimic living tissue matrices for tissue regeneration therapy. PMID- 26686470 TI - Monitoring the epitope recognition profiles of IgE, IgG1, and IgG4 during birch pollen immunotherapy. PMID- 26686469 TI - Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols. AB - S-nitrosothiols (SNOs) such as S-nitroso-L-cysteine (L-cysNO) are endogenous compounds with potent vasodilatory activity. During circulation in the blood, the NO moiety can be exchanged among various thiol-containing compounds by S transnitrosylation, resulting in SNOs with differing capacities to enter the cell (membrane permeability). To determine whether the vasodilating potency of SNOs is dependent upon membrane permeability, membrane-permeable L-cysNO and impermeable S-nitroso-D-cysteine (D-cysNO) and S-nitroso-glutathione (GSNO) were infused into one femoral artery of anesthetized adult sheep while measuring bilateral femoral and systemic vascular conductances. L-cysNO induced vasodilation in the infused hind limb, whereas D-cysNO and GSNO did not. L-cysNO also increased intracellular NO in isolated arterial smooth muscle cells, whereas GSNO did not. The infused SNOs remained predominantly in a low molecular weight form during first-passage through the hind limb vasculature, but were converted into high molecular weight SNOs upon systemic recirculation. At systemic concentrations of ~0.6 MUmol/L, all three SNOs reduced mean arterial blood pressure by ~50%, with pronounced vasodilation in the mesenteric bed. Pharmacokinetics of L-cysNO and GSNO were measured in vitro and in vivo and correlated with their hemodynamic effects, membrane permeability, and S-transnitrosylation. These results suggest local vasodilation by SNOs in the hind limb requires membrane permeation, whereas systemic vasodilation does not. The systemic hemodynamic effects of SNOs occur after equilibration of the NO moiety amongst the plasma thiols via S transnitrosylation. PMID- 26686471 TI - Early sensitization is associated with reduced lung function from birth into adulthood. PMID- 26686472 TI - Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study. AB - BACKGROUND: Sensitization to individual cat and dog allergen molecules can contribute differently to development of allergy to these animals. OBJECTIVE: We sought to investigate the association between sensitization patterns to cat and dog allergen molecules during childhood and symptoms to these furry animals up to age 16 years. METHODS: Data from 779 randomly collected children from the Barn/Children Allergy/Asthma Milieu Stockholm Epidemiologic birth cohort at 4, 8, and 16 years were used. IgE levels to cat and dog were determined by using ImmunoCAP, and levels to allergen molecules were determined by using an allergen chip based on ISAC technology (Mechanisms for the Development of Allergy chip). Allergy was defined as reported rhinitis, conjunctivitis, or asthma at exposure to cat or dog. RESULTS: Cross-sectionally, IgE to Fel d 1 and cat extract had similar positive predictive values for cat allergy. IgE to Can f 1 showed a higher positive predictive value for dog allergy than dog extract IgE. Sensitizations to Fel d 1 and Can f 1 in childhood were significantly associated with symptoms to cat or dog at age 16 years. Polysensitization to 3 or more allergen molecules from cat or dog was a better longitudinal predictor of cat or dog symptoms than results of IgE tests with cat or dog allergen extract, respectively. Cross-sectionally, cat/dog-polysensitized children had higher IgE levels and more frequent symptoms to cat and dog than monosensitized children. CONCLUSIONS: Sensitization to Fel d 1 and Can f 1 in childhood and polysensitization to either cat or dog allergen molecules predict cat and dog allergy cross-sectionally and longitudinally significantly better than IgE to cat or dog extract. PMID- 26686474 TI - RIG-G inhibits the proliferation of NB4 cells and propels ATRA-induced differentiation of APL cells. AB - RIG-G (retinoic acid-induced gene G) was originally identified in ATRA (all-trans retinoic acid)-treated NB4 acute promyelocytic leukemia (APL) cells. It was induced to expression by ATRA along with the differentiation of the cells. However, little is known about its role(s). Here, we established a RIG-G stably expression transformant of NB4 cells. By using the transformant, we showed that expression of RIG-G in NB4 cells not only arrested the cells at G1/G0 transition phase and inhibited their proliferation, but also markedly drive the maturation of NB4 cells in the presence of very low concentration of ATRA (10(-9)mol/L). What's more, by detecting the expression of RIG-G in fresh primary bone marrow mononuclear cells of APL patients in different morbid states, we found high RIG-G expression level in complete remission patients, while low level in untreated or relapsed patients. These results indicated that RIG-G level was high in maturated cells and low in blast cells, and suggested that RIG-G might play a role in the differentiation of bone marrow hemocytes in vivo. PMID- 26686473 TI - Caspase-11 and caspase-1 differentially modulate actin polymerization via RhoA and Slingshot proteins to promote bacterial clearance. AB - Inflammasomes are multiprotein complexes that include members of the NOD-like receptor family and caspase-1. Caspase-1 is required for the fusion of the Legionella vacuole with lysosomes. Caspase-11, independently of the inflammasome, also promotes phagolysosomal fusion. However, it is unclear how these proteases alter intracellular trafficking. Here, we show that caspase-11 and caspase-1 function in opposing manners to phosphorylate and dephosphorylate cofilin, respectively upon infection with Legionella. Caspase-11 targets cofilin via the RhoA GTPase, whereas caspase-1 engages the Slingshot phosphatase. The absence of either caspase-11 or caspase-1 maintains actin in the polymerized or depolymerized form, respectively and averts the fusion of pathogen-containing vacuoles with lysosomes. Therefore, caspase-11 and caspase-1 converge on the actin machinery with opposing effects to promote vesicular trafficking. PMID- 26686475 TI - Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group. AB - BACKGROUND AND OBJECTIVE: The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years. PATIENTS AND METHODS: In 2008, three prospective phase II trials in patients older than 55 years were activated: ALLOLD07 for Philadephia (Ph) chromosome-negative ALL, ALLOPH07 for Ph-positive ALL, and BURKIMAB08 for mature B-ALL. Early death (ED), complete remission (CR), disease-free survival (DFS), overall survival (OS) and toxicity were analyzed. RESULTS: 56, 53 and 21 patients from the ALLOLD07, ALLOPH07 and BURKIMAB08 trials, respectively, were evaluable. CR was 74%, 87% and 70%, with an ED rate of 13%, 11% and 15%, respectively. The medians of DFS were 8 and 38 months for ALLOLD07 and ALLOPH07 protocols, not being achieved in the BURKIMAB08 trial (p=0.001), and the median OS was 12, 37 and 25 months, respectively (p=0.030). Neutropenia, thrombocytopenia and infections were less frequent in the ALLOPH07 trial vs. ALLOLD07 and BURKIMAB trials, and renal toxicity and mucositis were more frequent in the BURKIMAB08 trial vs. the ALLOLD07 and ALLOPH07 trials. ECOG score and WBC count had prognostic significance for OS in ALLOPH07 and BURKIMAB08 trials, whereas no prognostic factors were identified in ALLOLD07 protocol. CONCLUSION: Subtype-oriented treatment had an impact in the outcome of older adults with ALL. The poorest outcome was observed in Ph-negative non-Mature B-cell ALL patients, for whom improvements in therapy are clearly needed. PMID- 26686476 TI - Guidelines for Creating, Implementing, and Evaluating Mind-Body Programs in a Military Healthcare Setting. AB - Research suggests that the development of mind-body skills can improve individual and family resilience, particularly related to the stresses of illness, trauma, and caregiving. To operationalize the research evidence that mind-body skills help with health and recovery, Samueli Institute, in partnership with experts in mind-body programming, created a set of guidelines for developing and evaluating mind-body programs for service members, veterans, and their families. The Guidelines for Creating, Implementing, and Evaluating Mind-Body Programs in a Military Healthcare Setting outline key strategies and issues to consider when developing, implementing, and evaluating a mind-body focused family empowerment approach in a military healthcare setting. Although these guidelines were developed specifically for a military setting, most of the same principles can be applied to the development of programs in the civilian setting as well. The guidelines particularly address issues unique to mind-body programs, such as choosing evidence-based modalities, licensure and credentialing, safety and contraindications, and choosing evaluation measures that capture the holistic nature of these types of programs. The guidelines are practical, practice-based guidelines, developed by experts in the fields of program development and evaluation, mind-body therapies, patient- and family-centered care, as well as, experts in military and veteran's health systems. They provide a flexible framework to create mind-body family empowerment programs and describe important issues that program developers and evaluators are encouraged to address to ensure the development of the most impactful, successful, evidence-supported programs possible. PMID- 26686477 TI - Hospitals Celebrate Food Day by Serving Meat Raised Without Antibiotics. PMID- 26686479 TI - Kinetics and microbial ecology of batch sulfidogenic bioreactors for co-treatment of municipal wastewater and acid mine drainage. AB - The kinetics and microbial ecology in sulfidogenic bioreactors used in a novel two-stage process for co-treatment of acid mine drainage (AMD) and municipal wastewater (MWW) were investigated. Michaelis-Menten modeling of COD oxidation by sulfate reducing bacteria (SRB) (Vmax=0.33mgL(-1)min(-1), Km=4.3mgL(-1)) suggested that the Vmax can be reasonably achieved given the typical COD values in MWW and anticipated mixing with AMD. Non-competitive inhibition modeling (Ki=6.55mgL(-1)) indicated that excessive iron level should be avoided to limit its effects on SRB. The COD oxidation rate was positively correlated to COD/sulfate ratio and SRB population, as evidenced by dsrA gene copies. Phylogenetic analysis revealed diverse microbial communities dominated by sulfate reducing delta-proteobacteria. Microbial community and relative quantities of SRB showed significant differences under different COD/sulfate ratios (0.2, 1 and 2), and the highest dsrA gene concentration and most complex microbial diversity were observed under COD/sulfate ratio 2. Major species were associated with Desulfovirga, Desulfobulbus, Desulfovibrio, and Syntrophus sp. The reported COD kinetics, SRB abundances and the phylogenetic profile provide insights into the co-treatment process and help identify the parameters of concerns for such technology development. PMID- 26686478 TI - Evaluation of bioremediation potentiality of ligninolytic Serratia liquefaciens for detoxification of pulp and paper mill effluent. AB - Due to high pollution load and colour contributing substances, pulp and paper mill effluents cause serious aquatic and soil pollution. A lignin-degrading bacterial strain capable of decolourising Azure-B dye was identified as lignin peroxidase (LiP) producing strain LD-5. The strain was isolated from pulp and paper mill effluent contaminated site. Biochemical and 16S rDNA gene sequence analysis suggested that strain LD-5 belonged to the Serratia liquefaciens. The strain LD-5 effectively reduced pollution parameters (colour 72%, lignin 58%, COD 85% and phenol 95%) of real effluent after 144h of treatment at 30 degrees C, pH 7.6 and 120rpm. Extracellular LiP produced by S. liquefaciens during effluent decolourisation was purified to homogeneity using ammonium sulfate (AMS) precipitation and DEAE cellulose column chromatography. The molecular weight of the purified lignin peroxidase was estimated to be ~28kDa. Optimum pH and temperature for purified lignin peroxidase activity were determined as pH 6.0 and 40 degrees C, respectively. Detoxified effluent was evaluated for residual toxicity by alkaline single cell (comet) gel electrophoresis (SCGE) assay using Saccharomyces cerevisiae MTCC 36 as model organism. The toxicity reduction to treated effluent was 49.4%. These findings suggest significant potential of S. liquefaciens for bioremediation of pulp and paper mill effluent. PMID- 26686480 TI - A robust localized soft sensor for particulate matter modeling in Seoul metro systems. AB - Developing accurate soft sensors to predict and monitor the indoor air quality (IAQ) of hazardous pollutants that accumulate in underground metro systems is of key importance. The just-in-time (JIT) learning technique possesses a local feature that can track the variations in the dynamic process more effectively, which is different from the traditional soft sensor modeling methods, such as partial least squares (PLS), which models the process in an offline and global way. In this study, a robust soft sensor that combined the JIT learning technique with a least squares support vector regression (LSSVR) method, named JIT-LSSVR, was derived in order to improve the prediction performance of a PM2.5 soft sensor in a subway station. Additionally, in order to eliminate the adverse effects caused by the outliers in the process variables, an outlier detection step was integrated into the JIT-LSSVR modeling procedure. The performance evaluation results demonstrated that the proposed robust JIT-LSSVR soft sensor has the capability to model nonlinear and dynamic subway systems. The root mean square error of the JIT-LSSVR soft sensor was improved by 55% in comparison with that of the LSSVR soft sensor. PMID- 26686481 TI - Toxicity and bioaccumulation of copper in Limnodrilus hoffmeisteri under different pH values: Impacts of perfluorooctane sulfonate. AB - Aquatic oligochaete Limnodrilus hoffmeisteri (L. hoffmeisteri) has been commonly used as a lethal and/or sub-lethal toxicological model organism in ecological risk assessments in contaminated water environments. In this study, experiments were conducted to investigate the potential toxic effects of copper (Cu(II)) with or without perfluorooctane sulfonate (PFOS) under different pH values (6.0, 7.0 and 8.0) on LC50, bioaccumulation, and oxidative stress biomarkers in L. hoffmeisteri after 3 and 7 days. The LC50 values of Cu(II) decreased with the increasing pH and the addition of PFOS. After each exposure, increasing bioaccumulation of Cu(II) in L. hoffmeisteri was observed in the combined exposure treatments, whereas the bioaccumulation of PFOS decreased. Moreover, the activity of superoxide dismutase, the level of glutathione, and the content of malondialdehyde were significantly altered after these exposures, possibly indicating that the bioaccumulation of Cu(II) and PFOS caused adverse effects on antioxidant defenses of L. hoffmeisteri. The integrated biomarker response index, indicates that the combined effect was proposed as synergism, which is coincided with the results of toxic unit. Moreover, this work showed that aquatic environment may become more livable when water conditions changed from acidic to near-neutral or alkaline. PMID- 26686482 TI - Kinetics and mechanism investigation on the destruction of oxytetracycline by UV 254nm activation of persulfate. AB - Oxytetracycline (OTC), an important broad-spectrum antibiotic, has been detected extensively in various environmental systems, which may have a detrimental impact on ecosystem and human health through the development of drug resistant bacteria and pathogens. In this study, the degradation of OTC was evaluated by UV-254nm activated persulfate (PS). The observed UV fluence based pseudo first-order rate constant (kobs) was found to be the highest at near neutral pH conditions (pH 5.5 8.5). Presence of various natural water constituents had different effects on OTC degradation, with a significant enhancement in the presence of bicarbonate or Cu(2+). Limited elimination of total organic carbon (TOC) and PS was observed during the mineralization of OTC. Transformation byproducts in the presence and absence of hydroxyl radical scavenging agent tert-butanol (t-BuOH) were identified using ultra-high definition accurate-mass quadrupole time-of-flight liquid chromatography/mass spectrometer (LC-QTOF/MS). Potential OTC degradation mechanism was subsequently proposed revealing four different reaction pathways by SO4(-) reaction including hydroxylation (+16Da), demethylation (-14Da), decarbonylation (-28Da) and dehydration (-18Da). This study suggests that UV 254nm/PS is a promising treatment technology for the control of water pollution caused by emerging contaminants such as OTC. PMID- 26686483 TI - A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil. AB - Polycyclic Aromatic Hydrocarbons are classed as Persistent Organic Pollutants, a large group of compounds that share similar characteristics. They are lipophilic, resistant to degradation in the environment and harmful to human and environmental health. Soil has been identified as the primary reservoir for Polycyclic Aromatic Hydrocarbons in the United Kingdom. This study reviews the literature associated with, or is relevant to, the measurement and modelling of dermal absorption of Polycyclic Aromatic Hydrocarbons from soils. The literature illustrates the use of in vivo, in vitro and in silico methods from a wide variety of scientific disciplines including occupational and environmental exposure, medical, pharmaceutical and cosmetic research and associated mathematical modelling. The review identifies a number of practical shortcomings which must be addressed if dermal bioavailability tests are to be applied to laboratory analysis of contaminated soils for human health risk assessment. PMID- 26686484 TI - Synthesis of empty african horse sickness virus particles. AB - As a means to develop African horse sickness (AHS) vaccines that are safe and DIVA compliant, we investigated the synthesis of empty African horse sickness virus (AHSV) particles. The emphasis of this study was on the assembly of the major viral core (VP3 and VP7) and outer capsid proteins (VP2 and VP5) into architecturally complex, heteromultimeric nanosized particles. The production of fully assembled core-like particles (CLPs) was accomplished in vivo by baculovirus-mediated co-synthesis of VP3 and VP7. The two different outer capsid proteins were capable of associating independently of each other with preformed cores to yield partial virus-like particles (VLPs). Complete VLPs were synthesized, albeit with a low yield. Crystalline formation of AHSV VP7 trimers is thought to impede high-level CLP production. Consequently, we engineered and co-synthesized VP3 with a more hydrophilic mutant VP7, resulting in an increase in the turnover of CLPs. PMID- 26686485 TI - Relaxed Poisson cure rate models. AB - The purpose of this article is to make the standard promotion cure rate model (Yakovlev and Tsodikov, ) more flexible by assuming that the number of lesions or altered cells after a treatment follows a fractional Poisson distribution (Laskin, ). It is proved that the well-known Mittag-Leffler relaxation function (Berberan-Santos, ) is a simple way to obtain a new cure rate model that is a compromise between the promotion and geometric cure rate models allowing for superdispersion. So, the relaxed cure rate model developed here can be considered as a natural and less restrictive extension of the popular Poisson cure rate model at the cost of an additional parameter, but a competitor to negative binomial cure rate models (Rodrigues et al., ). Some mathematical properties of a proper relaxed Poisson density are explored. A simulation study and an illustration of the proposed cure rate model from the Bayesian point of view are finally presented. PMID- 26686486 TI - Subtotal gastrectomy for diffused hemorrhagic gastritis induced by radiation, following liver resection for hilar cholangiocarcinoma. A case report. AB - INTRODUCTION: A rare case of hemorrhagic gastritis induced by radiation is presented, which was resistant to conservative treatment and required subtotal gastrectomy. PRESENTATION OF CASE: A 56-year-old male was initially undergone right hepatectomy, resection of the extrahepatic biliary tree, hilar lymph node dissection and hepatico-jejunostomy due to advanced hilar cholangiocarcinoma. Because of the extent of the disease, chemo-radiotherapy was administered. The patient received a total radiotherapy dose of 57.6Gy in 32 sessions. Unfortunately, diffused hemorrhagic gastritis induced by radiation was developed, which was resistant to conservative treatment (endoscopic hemostasis, transfusion). A subtotal gastrectomy was performed. The patient is in good condition 45 months after the liver resection, but with local recurrence. CONCLUSION: In resistant situations to conservative treatment and recurred bleeding of diffused hemorrhagic gastritis induced by radiation, surgical management may have a role. PMID- 26686487 TI - HAART toxicity masquerading as a surgical abdomen. AB - INTRODUCTION: Intussusception is a rare disease in adults and poses a challenge to identify and manage. In adults, surgical resection is the preferred treatment since half are due to malignancy. This case reveals an association between highly active antiretroviral therapy (HAART) and intussusception. PRESENTATION OF CASE: A 44 year-old female with history of HIV on highly active antiretroviral therapy (HAART) presented with 3 month history of epigastric pain, nausea, emesis, weight loss, and lactic acidosis. CT of abdomen showed two small bowel intussusceptions and pericolic fat infiltration. A diagnosis of mitochondrial toxicity secondary to HAART medication was made. HAART medication was discontinued with resolution of symptoms. Further work-up to exclude a mechanical cause for her symptoms including colonoscopy, small bowel follow through, esophagogastroduodenoscopy, and repeat CT were performed. All established an absence of malignancy and intussusception. DISCUSSION: Mitochondrial toxicity (MT) is a well-known complication of HAART. A hallmark of MT is lactic acidosis which when untreated can be fatal. Although MT is known to cause gastrointestinal symptoms, intussusception has not been previously reported. In our patient with MT, prolonged usage of HAART medication resulted in severe gastrointestinal symptoms and intussusception mimicking a surgical abdomen. Laparotomy has been recommended on adult patients with intussusceptions because of the high likelihood of identifying a pathologic lesion. The doctrine of adult intussusception is to operate for concern of malignancy. CONCLUSION: Surgeons, gastroenterologist and internist caring for patients on HAART therapy must be aware of the possibility of MT when evaluating HIV patients for possible surgical abdomen. PMID- 26686488 TI - Unusual presentation of gallbladder perforation. AB - INTRODUCTION: Gall bladder perforation is associated with high mortality rates and therefore must be recognised and managed promptly. We present an unusual presentation of spontaneous gall bladder perforation. CASE PRESENTATION: An elderly lady with multiple medical co-morbidities was admitted with sepsis following a fall. Initial assessment lead to a diagnosis of pneumonia, however a rapidly expanding right flank mass was incidentally noted during routine nursing care. Imaging studies were inconclusive, however incision and drainage of the mass revealed bile stained pus draining cutaneously from an acutely inflamed gallbladder. The patient made a good recovery following surgery, and was discharged with outpatient follow-up. DISCUSSION: Despite focussed post-hoc history taking she denied any prodromal symptoms of cholecystitis. In addition to reporting an unusual cause for a common presentation, we highlight the importance of a full body examination in the context of sepsis, regardless of whether the source has been identified. In addition, we advocate that surgical intervention in sepsis should not be delayed by imaging in cases where an abscess is suspected. CONCLUSIONS: Percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis, and may present in a wide variety of locations. Therefore it is imperative to conduct a full body inspection in the septic patient, even when a source has been identified. PMID- 26686489 TI - Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas. AB - Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, beta-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion. PMID- 26686490 TI - The Association among Childhood Trauma, Pathological Dissociation and Gambling Severity in Casino Gamblers. AB - : The aim of the present study was to explore the role of pathological dissociation in mediating the association between childhood trauma (CT) and gambling severity. One hundred seventy-one (134 men and 37 women) gamblers recruited in gambling environments (i.e., two Italian casinos) have been enrolled in the study. Psychopathological assessments included the Childhood Trauma Questionnaire (CTQ), the Dissociative Experiences Scale-Taxon (DES-T), the South Oaks Gambling Screen (SOGS), the CAGE and the Hospital Anxiety and Depression Scale. A mediational model, analyzing the direct and indirect effects of CTQ on SOGS through the mediating role of DES-T, showed that the relation between CTQ and SOGS was fully mediated by DES-T scores (b = 0.07; se = 0.15; p < 0.001). This finding raises the possibility that CT explains gambling severity through the presence of pathological dissociative symptoms and dissociative pathogenetic processes. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Gambling severity is associated with both childhood trauma and pathological dissociation in casino gamblers. A mediational model shows that the effect of childhood trauma on gambling severity is entirely mediated by pathological dissociation. From a clinical point of view, our results highlight the importance of assessing, and possibly treating, dissociative symptoms in individuals with gambling disorder. PMID- 26686491 TI - The 17th International Symposium on Recent Advances in Drug Delivery, June 14-17, 2015, Salt Lake City, UT, USA. Preface. PMID- 26686492 TI - Reprint of: Nitric oxide-releasing polysaccharide derivative exhibits 8-log reduction against Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. AB - Health-care associated infections (HAIs) and the increasing number of antibiotic resistant bacteria strains remain significant public health threats worldwide. Although the number of HAIs has decreased by using improved sterilization protocols, the cost related to HAIs is still quantified in billions of dollars. Furthermore, the development of multi-drug resistant strains is increasing exponentially, demonstrating that current treatments are inefficient. Thus, the quest for new methods to eradicate bacterial infection is increasingly important in antimicrobial, drug delivery and biomaterials research. Herein, the bactericidal activity of a water-soluble NO-releasing polysaccharide derivative was evaluated in nutrient broth media against three bacteria strains that are commonly responsible for HAIs. Data confirmed that this NO-releasing polysaccharide derivative induced an 8-log reduction in bacterial growth after 24h for Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Additionally, the absence of bacteria after 72 h of exposure to NO illustrates the inability of the bacteria to recover and the prevention of biofilm formation. The presented 8-log reduction in bacterial survival after 24h is among the highest reduction reported for NO delivery systems to date, and reaches the desired standard for industrially-relevant reduction. More specifically, this system represents the only water-soluble antimicrobial to reach such a significant bacterial reduction in nutrient rich media, wherein experimental conditions more closely mimic the in vivo environment than those in previous reports. Furthermore, the absence of bacterial activity after 72 h and the versatility of using a water-soluble compound suggest that this NO-releasing polysaccharide derivative is a promising route for treating HAIs. PMID- 26686493 TI - Minimally invasive plate osteosynthesis in proximal humeral fractures: one-year results of a prospective multicenter study. AB - PURPOSE: The aim of this multicentric study was to evaluate results of minimally invasive plate osteosynthesis (MIPO) for proximal humeral fractures in terms of postoperative shoulder function, radiological outcome and number of complications. METHODS: A consecutive series of 76 patients with proximal humeral fractures were treated with locking plate using a minimally invasive antero lateral approach in two orthopaedic departments. Functional results with Constant score and radiographic evaluation were available for 74 patients at one-year follow up. RESULTS: The patients achieved a mean Constant score of 71 (range 28 100). Each functional result was evaluated also for both centres without significant differences. Significant statistical differences were only found for younger patients with better results (p < 0.05). Twenty patients (27%) developed complications. Subacromial impingement occurred in 16.2% of cases for varus malreduction (6.7%) and for too proximal plate positioning (9.5%). Primary screws perforation (2.7%), secondary perforation due to cut-out (1.4%), avascular necrosis (AVN) of humeral head (1.4%), partial resorption of greater tuberosity (2.7%), secondary dislocation of the greater tuberosity (2.7%) and stiffness (2.7%) were the other complications observed. CONCLUSIONS: The MIPO technique for proximal humeral fractures was safe and reproducible for most common patterns of fracture. Major complication rate was apparently low due to a soft tissue sparing, deltoid muscle and circumflex vessels, with easy access of the bar area to correct positioning of the plate. PMID- 26686494 TI - Comment on Piatkowski et al.: Comparison of different locking plate fixation methods in distal tibia fractures. PMID- 26686495 TI - Retrospective comparative study shows no significant difference in postural stability between cruciate-retaining (CR) and cruciate-substituting (PS) total knee implant systems. AB - PURPOSE: Modified postural stability after retaining the posterior cruciate ligament (PCL) in total knee arthroplasty is still discussed controversially. The objective of this study was to evaluate whether a PCL-retaining implant design should be preferred over a PCL-substituting implant design regarding postural stability in one-leg stance and clinical outcome. METHODS: Forty patients underwent total knee arthroplasty, 20 of them with a cruciate-retaining (CR) and 20 of them with a cruciate-substituting (PS) implant system. Postural stability was analysed 6 months postoperatively in one-leg stance using the Biodex Balance System. In addition, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee Society Score were completed. RESULTS: This study shows that there is no significant difference in postural stability between CR and PS) implant systems with PS implants showing better results in WOMAC score. CONCLUSIONS: In case it is necessary to use a PS implant, no negative influence on postural stability is to be expected compared to a CR implant. PMID- 26686496 TI - Pure elbow dislocation in the paediatric age group. AB - PURPOSE: The main purpose of the present study was to evaluate the clinical results and prognosis of pure elbow dislocations in the paediatric age group following non-surgical treatment. METHODS: Acute traumatic pure elbow dislocations treated between January 2008 and January 2013 were evaluated. The median age was eight years. The mean follow-up time was 46 months. Active and passive range of motion (ROM), elbow stability, neurovascular status, functional status and any early or late complications were evaluated and recorded at the latest follow-up. RESULTS: The mean flexion-extension ROM was measured as 119.5 degrees. The mean pronation and supination were 67 and 79 degrees. Moderate instability was diagnosed in four cases. The mean Mayo Elbow Performance Score (MEPS) score was 91.6 points; the clinical outcome was excellent in nine patients, good in two and fair in one. CONCLUSIONS: Acute traumatic pure elbow dislocation in childhood is a very rarely seen emergency that can be treated safely with closed reduction combined long-arm plaster splinting and physical rehabilitation. PMID- 26686497 TI - Management of combined atlas-axis fractures: a review of forty one cases. AB - PURPOSE: To outline a management principle for the combined atlas (C1)-axis (C2) fractures and assess its therapeutic effects. METHODS: Forty-one patients with combined C1-C2 fractures were treated according to their C2 fracture types. Non operative external immobilization in the form of a cervical collar or halo vest was used in 22 patients. Early posterior pedicle screw fixations were performed in 19 patients whose fractures had a combination of any of the three conditions: an atlantodens interval (ADI) >= 5 mm, lateral mass displacement (LMD) > 7 mm, and/or C2-C3 angulation > 11 degrees . Thirty-nine patients were followed up regularly with an average of 19.3 months (range, 12 to 45 months). Clinical and radiographic data were then collected and compared. RESULTS: At three months following treatment, patients' visual analog scale (VAS), Neck Disability Index (NDI), American Spinal Injury Association (ASIA) scale, and Frankel grades were all significantly improved when compared to pretreatment. These results indicated that the cervical collar, halo vest, and posterior pedicle screw fixation approaches were all able to effectively treat cases of combined C1-C2 fractures. One patient in the non-surgical group developed nonunion which required late surgical treatment and one patient had pin site infection in the non-surgical group (2/22), while there were three minor complications in the surgical group. CONCLUSION: We propose a management principle that bases the treatment of a combined C1-C2 fracture on the nature of the C2 fracture. This treatment strategy has yielded promising results as a satisfactory means for the management of combined C1-C2 fractures. PMID- 26686498 TI - Risk factors and a prognostic model of hip periprosthetic infection recurrence after surgical treatment using articulating and non-articulating spacers. AB - PURPOSE: The purpose of this study was evaluation of the efficacy of the first step of a two-stage procedure for treatment of hip prosthetic joint infection (PJI) using articulating and non-articulating spacers as well as development of a prediction model and prognostic score for infection recurrence. METHODS: In a cohort of 217 patients treated for PJI of the hip, demographic characteristics, clinical symptoms, body temperature, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC), microbiological cultures and the type of the spacer used were retrospectively analyzed for association with the recurrence of PJI. RESULTS: Patients with infection recurrence had increased levels of ESR and CRP (P < 0.001) together with higher BMI and shorter infection manifestation period after previous surgery (P < 0.05). Among these patients, there was no significant difference of clinical characteristics between subjects with articulating and non-articulating spacers. Microbial associations were more often identified in patients with recurrent infection (50 %, P < 0.01) where Gram-negative bacteria were predominant (61.5 %, P < 0.01). These patients had higher percentage of Acinetobacter sp. and P. aeruginosa isolates (28.2 %, P < 0.01). CONCLUSIONS: Efficacy of the first step of two-stage revision was 64.1 %. Placement of either articulating or non articulating spacers did not influence recovery from PJI. Laboratory values of ESR, CRP, BMI and the type of previous surgery were identified as main factors that affect outcomes of the two-stage procedure. A prognostic model with the calculation of a total risk score for PJI recurrence was developed. PMID- 26686499 TI - Electrospun Polyvinyl Alcohol/ Pluronic F127 Blended Nanofibers Containing Titanium Dioxide for Antibacterial Wound Dressing. AB - In this study, an antibacterial electrospun nanofibers for wound dressing application was successfully prepared from polyvinyl alcohol (PVA), Pluronic F127 (Plur), polyethyleneimine (PEI) blend solution with titanium dioxide nanoparticles (TiO2 NPs). PVA-Plur-PEI nanofibers containing various ratios of TiO2 NPs were obtained. The formation and presence of TiO2 in the PVA-Plu-PEI/ TiO2 composite was confirmed by X-ray diffraction (XRD). Transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), mechanical measurement, and antibacterial activity were undertaken in order to characterize the PVA-Plur-PEI/TiO2 nanofiber morphology and properties. The PVA-Plu-PEI nanofibers had a mean diameter of 220 nm, and PVA-Plur-PEI/TiO2 nanofibers had 255 nm. Moreover, the antimicrobial properties of the composite were studied by zone inhibition against Gram-negative bacteria, and the result indicates high antibacterial activity. Results of this antibacterial testing suggest that PVA-Plur-PEI/TiO2 nanofiber may be effective in topical antibacterial treatment in wound care; thus, they are very promising in the application of wound dressings. PMID- 26686500 TI - The Stability Enhancement of Nitrile Hydratase from Bordetella petrii by Swapping the C-terminal Domain of beta subunit. AB - The thermal stability of most nitrile hydratases (NHase) is poor, which has been enhanced to some extent by molecular modifications in several specific regions of the C-terminal domain (C-domain) of beta subunit of NHase. Since the C-domain could be present as a naturally separate domain in a few NHases, the whole C domain is proposed to be related to the NHase stability. The chimeric NHase (SBpNHase) from the thermal-sensitive BpNHase (NHase from Bordetella petrii) and the relatively thermal-stable PtNHase (NHase from Pseudonocardia thermophila) was constructed by swapping the corresponding C-domains. After 30 min incubation at 50 degrees C, the original BpNHase nearly lost its activity, while the SBpNHase retained 50 % residual activity, compared with the melting temperature (Tm) (50 degrees C) of the original BpNHase, that of the SBpNHase was 55 degrees C. The SBpNHase with higher thermal stability would be useful for the thermal stability enhancement of NHase and for the understanding of the relationship between the stability of NHase and its structure. PMID- 26686501 TI - Therapeutic Dose Monitoring for Linezolid in a Patient with MRSA Pneumonia with Bacteremia in Diabetes Insipidus. AB - INTRODUCTION: Few studies have investigated the effect of increased creatinine clearance (CrCl) on linezolid (LZD) concentration. Herein, we report the pharmacokinetic/pharmacodynamic (PK/PD) profile of LZD used in the management of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia with concomitant bacteremia in a patient with high CrCl caused by diabetes insipidus (DI). CASE REPORT: A 19-year-old man was admitted to the intensive care unit following a traumatic brain injury. After admission, he underwent a craniotomy for the severe brain injury. However, he developed DI after the operation. Despite treatment with vasopressin, his urine output reached 5-6 L/day as a result of the DI, and his CrCl increased to 180-278 mL/min. We were required to administer 6-7 L of fluid a day to compensate for the high urinary fluid output. On day 55, MRSA pneumonia with sepsis was suspected and, consequently, LZD was administrated intravenously (600 mg every 12 h). He was treated with LZD for 14 days. The patient has since successfully recovered from MRSA pneumonia with concomitant bacteremia, and was transferred to the general ward on day 82. Blood LZD levels from days 60-68, which were measured after the patient's transfer to the general ward, showed that the trough levels were lower than the threshold level of detection. The blood 24-h area under the plasma LZD concentration-time curve (AUC)24/minimum inhibitory concentration (MIC) was 69.3. CONCLUSION: In spite of the low level of LZD AUC24/MIC caused by the high CrCl with DI, MRSA pneumonia with concomitant bacteremia was successfully treated with LZD. PMID- 26686502 TI - Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. AB - Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ) injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1beta and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-alpha, IL-1beta and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. PMID- 26686503 TI - Expanding the phenotype in aminoacylase 1 (ACY1) deficiency: characterization of the molecular defect in a 63-year-old woman with generalized dystonia. AB - Aminoacylase 1 (ACY1) deficiency is an organic aciduria due to mutations in the ACY1 gene. It is considered much underdiagnosed. Most individuals known to be affected by ACY1 deficiency have presented with neurologic symptoms. We report here a cognitively normal 63-year-old woman who around the age of 12 years had developed dystonic symptoms that gradually evolved into generalized dystonia. Extensive investigations, including metabolic diagnostics and diagnostic exome sequencing, were performed to elucidate the cause of dystonia. Findings were only compatible with a diagnosis of ACY1 deficiency: the urinary metabolite pattern with N-acetylated amino acids was characteristic, there was decreased ACY1 activity in immortalized lymphocytes, and two compound heterozygous ACY1 mutations were detected, one well-characterized c.1057C>T (p.Arg353Cys) and the other novel c.325A>G (p.Arg109Gly). Expression analysis in HEK293 cells revealed high residual activity of the enzyme with the latter mutation. However, following co-transfection of cells with stable expression of the c.1057C>T variant with either wild-type ACY1 or the c.325A>G mutant, only the wild-type enhanced ACY1 activity and ACY1 presence in the Western blot, suggesting an inhibiting interference between the two variants. Our report extends the clinical spectrum of ACY1 deficiency to include dystonia and indicates that screening for organic acidurias deserves consideration in patients with unexplained generalized dystonia. PMID- 26686504 TI - Regenerating a kidney in a lymph node. AB - The ultimate treatment for end-stage renal disease (ESRD) is orthotopic transplantation. However, the demand for kidney transplantation far exceeds the number of available donor organs. While more than 100,000 Americans need a kidney, only 17,000 people receive a kidney transplant each year (National Kidney Foundation's estimations). In recent years, several regenerative medicine/tissue engineering approaches have been exploited to alleviate the kidney shortage crisis. Although these approaches have yielded promising results in experimental animal models, the kidney is a complex organ and translation into the clinical realm has been challenging to date. In this review, we will discuss cell therapy based approaches for kidney regeneration and whole-kidney tissue engineering strategies, including our innovative approach to regenerate a functional kidney using the lymph node as an in vivo bioreactor. PMID- 26686505 TI - Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods. AB - Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group. PMID- 26686506 TI - The effects of copper pyrithione, an antifouling agent, on developing zebrafish embryos. AB - A substitute for the organotins has been the use of metal pyrithiones, principally zinc and copper (CuPT) as antifouling agents. Zebrafish, Danio rerio, embryos were exposed after fertilization to increasing concentrations of CuPT (2, 4, 8, 12, 16, 32 and 64 MUg/L) for 24 h. Morphological abnormalities at 30, 96 and 120 hours post fertilization (hpf) were recorded. Abnormalities at concentrations of 12 MUg/L and higher were observed. Notochords became severely twisted as concentrations increased. These distortions of the notochord originated in the tail at the lower concentrations and proceeded rostrally with increasing dose. Edema was observed in the cardiac and yolk sac regions at the 12 and 16 MUg/L CuPT concentrations. Light microscopy showed disorganization of muscle fibers, disruption and distortion of the transverse myoseptum and vacuolization of the myocyte. Hatching was measured every 12 h for 5 days following the 24 h exposure. Hatching decreased in a dose dependent manner. At 120 hpf, 47 % of the 64 MUg/L CuPT treated embryos hatched. Inductively coupled plasma atomic absorbance spectrophotometry (ICPAAS) revealed copper bioaccumulation in whole embryo tissue and was significantly elevated in 32 and 64 MUg/L CuPT treatment groups as compared to controls. Lipid peroxidation end products were significantly increased in animals exposed to 32 and 64 MUg/L of CuPT. These data demonstrate that oxidative stress may play a role in the toxicity. The abnormalities and deformities observed in fish larvae would significantly decrease survival in polluted aqua-systems and question the use of this product as an antifouling agent. PMID- 26686507 TI - Measuring cytochrome P450 activity in aquatic invertebrates: a critical evaluation of in vitro and in vivo methods. AB - The first step in xenobiotic detoxification in aquatic invertebrates is mainly governed by the cytochrome P450 mixed function oxidase system. The ability to measure cytochrome P450 activity provides an important tool to understand macroinvertebrates' responses to chemical stressors. However, measurements of P450 activity in small aquatic invertebrates have had variable success and a well characterized assay is not yet available. The general lack of success has been scarcely investigated and it is therefore the focus of the present work. In particular, the suitability of the substrate selected for the assay, the sensitivity of the assay and the possible inhibition/attenuation of enzymatic activity caused by endogenous substances were investigated. 7-ethoxycoumarin-O dealkylation activity of Daphnia magna, Chironomus riparius larvae and Hyalella azteca was assessed in vivo and in vitro and possible inhibition of enzymatic activity by macroinvertebrates homogenate was investigated. Activities of D. magna and C. riparius larvae measured in vivo were 1.37 +/- 0.08 and 2.2 +/- 0.2 pmol h(-1) organism(-1), respectively, while activity of H. azteca could not be detected. In vitro activity could be measured in C. riparius larvae only (500 1000 pmol h(-1) mg microsomal protein(-1)). The optimization of the in vitro assay has been especially long and resource consuming and particularly for D. magna, substances that inhibited cytochrome P450 activity seemed to be released during tissue homogenization preventing activity measurements in vitro. We therefore recommend testing the P450 inhibition potential of homogenate preparations prior to any investigation of P450 activity in vitro in macroinvertebrates. PMID- 26686508 TI - The immunogenicity, safety, and consistency of an Indonesia combined DTP-HB-Hib vaccine in expanded program on immunization schedule. AB - BACKGROUND: WHO recommended incorporation of Haemophilus influenzae type b (Hib) vaccination into immunization program. Indonesia would adopt Hib as a National Immunization Program in 2013. We aimed at analyzing immunogenicity, safety, and consistency of a new combined DTP-HB-Hib (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenza B) vaccine. METHODS: A prospective, randomized, double blind, multicenter, phase III study of Bio Farma DTP-HB-Hib vaccine conducted in Jakarta and Bandung, August 2012 - January 2013. Subjects were divided into three groups with different batch number. Healthy infants 6-11 weeks of age at enrollment were immunized with 3 doses of DTP-HB-Hib vaccine with interval of 4 weeks, after birth dose of hepatitis B vaccine. Blood samples obtained prior to vaccination and 28 days after the third dose. Safety measures recorded until 28 days after each dose. RESULTS: Of 600 subjects, 575 (96 %) completed study protocol. After 3 doses, 100.0 and 96.0 % had anti-PRP concentration >=0.15 and >=1.0 MUg/ml. Anti-diphtheria and anti-tetanus concentration >=0.01 IU/ml detected in 99.7 and 100.0 %; while concentration >=0.1 IU/ml achieved in 84.0 and 97.4 %. Protective anti-HBs found in 99.3 %. The pertussis vaccine response rate was 84.9 %. None Serious Adverse events (SAEs) considered related to study vaccine or procedure. CONCLUSIONS: The 3-dose of DTP-HB-Hib was immunogenic, well tolerated and suitable for replacement of licensed-equivalent vaccines based on immunologic and safety profiles. TRIAL REGISTRATION: NCT01986335 - October 30(th) 2013. PMID- 26686509 TI - PEEP titration during prone positioning for acute respiratory distress syndrome. AB - No major trial evaluating prone positioning for acute respiratory distress syndrome (ARDS) has incorporated a high-positive end-expiratory pressure (high PEEP) strategy despite complementary physiological rationales. We evaluated generalizability of three recent proning trials to patients receiving a high-PEEP strategy. All trials employed a relatively low-PEEP strategy. After protocol ventilator settings were initiated and the patient was positioned per treatment assignment, post-intervention PEEP was not more than 5 cm H2O in 16.7 % and not more than 10 cm H2O in 66.0 % of patients. Post-intervention PEEP would have been nearly twice the set PEEP had a high-PEEP strategy been employed. Use of either proning or high-PEEP likely improves survival in moderate-severe ARDS; the role for both concomitantly remains unknown. PMID- 26686510 TI - Evidence-based management of vitiligo: summary of a Cochrane systematic review. AB - Vitiligo affects around 1% of the world's population. Despite it being relatively common, there is still no effective treatment. The objective of this study was to update the Cochrane systematic review of randomized clinical trials (RCTs) to evaluate the efficacy of treatments for vitiligo. We carried out searches of a range of databases to October 2013 for RCTs of interventions for vitiligo regardless of language or publication status. At least two reviewers independently assessed study eligibility and methodological quality and extracted data using data extraction forms approved by the Cochrane Skin Group. Our primary outcomes of interest were quality of life, > 75% repigmentation and adverse effects. We retrieved 96 studies, of which 39 were new studies, with an overall total of 4512 participants. Repigmentation was assessed in all studies, although only five reported on all three of our primary outcomes. Regarding our two secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation at 2 years' follow-up. Most of the studies evaluated combination treatments, which generally showed better repigmentation than monotherapies. Of the new studies, seven were surgical interventions. The majority of the studies had fewer than 50 participants. The quality of the studies was poor to moderate at best. Very few studies specifically included children or participants with segmental vitiligo. Five years after the last update of this review, there are still important variations in study design and outcome measures in clinical trials for vitiligo, limiting the evidence for the efficacy of different therapeutic options. The best evidence from individual trials showed short-term benefit from topical corticosteroids and various forms of ultraviolet radiation combined with topical preparations. Long-term follow-up and patient-rated outcomes should be incorporated into study design, and more studies should assess psychological interventions. PMID- 26686511 TI - Normal immunofluorescence pattern of skin basement membranes in a family with porencephaly due to COL4A1 G749S mutation. AB - COL4A1 mutations have been associated with cerebral small-vessel disease, including perinatal intracerebral hemorrhage with consequent porencephaly, microbleeds, and lacunar strokes. Moreover, involvement of multiple organs and tissues like kidney, muscle, and large vessels have been reported. Three related patients with porencephaly bearing the G749S mutation in the COL4A1 gene and one healthy control belonging to the same family underwent skin biopsy. Tissue was examined by means of immunofluorescence microscopy and immunoreactivity for collagen type IV in skin basement membranes was tested. In subjects with COL4A1 mutation, we did not detect significant alterations of immunofluorescence patterns in basal membranes of different skin structures. Heterozygous COL4A1 G749S mutation is associated with a normal immunofluorescence pattern of skin basement membranes. Further studies are needed to clarify the role of possible functional abnormalities of the basement membranes in patients with this mutation. PMID- 26686512 TI - Collagen crosslinking in the management of leaking cystic blebs: a prospective study. AB - PURPOSE: To evaluate the effectiveness and safety of collagen crosslinking for leaking cystic blebs. METHODS: A prospective study was conducted on subjects with cystic bleb leaks without indications for urgent surgical intervention. Collagen crosslinking with riboflavin 0.1 % and ultraviolet A irradiation for 30 min was applied to the cystic bleb surface in five patients. Subjects were followed up for at least 20 weeks (mean: 35.5 +/- 11.5 weeks) to monitor the length of time to the cessation of bleb leak, as well as visual acuity, intraocular pressure, and the presence of adverse effects arising from the treatment. RESULTS: Results showed that a single session of collagen crosslinking was effective in stopping cystic bleb leak. In two of the five subjects, the bleb leak subsided 1 week post treatment, in one patient after 2 weeks, and in the two more complicated cases, after 4 weeks. This effect was maintained for a mean period of 33.5 +/- 10.2 weeks after bleb leak cessation. Treatment was effective even in patients with friable conjunctiva following multiple surgical interventions and severe leak, although a longer period was needed for resolution of the bleb leak. The intraocular pressure and visual acuity were largely stable before and after treatment. No side effects or complications arose from this treatment. CONCLUSIONS: We recommend a trial of collagen crosslinking on leaking cystic blebs without indications for immediate surgical interventions. It is a relatively easy, non-invasive, pain-free, and potential repeatable procedure for treating leaking cystic blebs, with the aim of strengthening the underlying pathological conjunctiva. PMID- 26686513 TI - Cycloplegic autorefraction in young adults: is it mandatory? AB - PURPOSE: The precise correction of refractive error is especially important in young adults. It is unclear whether cycloplegic refraction is necessary in this age group. The purpose of this study was to compare the non-cycloplegic and cycloplegic spherical equivalent (SE) refractive error measured in young adults. METHODS: This was a prospective study of 1400 eyes (n = 700) of enlisted soldiers aged 18 to 21 years who were consecutively evaluated in an outpatient army ophthalmology clinic. One drop of cyclopentolate 1 % was installed twice 10 min apart, and cycloplegic refraction was performed in both eyes 40 min later using an auto-refractor. The difference between non-cycloplegic and cycloplegic refractive measurements was analyzed. RESULTS: The mean difference in SE between non-cycloplegic and cycloplegic measurements was 0.68 +/- 0.83 D (95 % CI, 0.64 0.72). Significantly greater differences were observed in hypermetropes than myopes (1.30 +/- 0.90 D versus 0.46 +/- 0.68 D, p < 0.001). Moderate hypermetropes (2 to 5 D) demonstrated significantly greater refractive error than mild (0.5 to 2 D) or severe (>5 D) hypermetropes (1.71 +/- 1.18 D versus 1.19 +/- 0.74 D and 1.16 +/- 1.08 D respectively, p < 0.001). CONCLUSIONS: Young hypermetropic adults possessed +1 to +2 D of latent hypermetropia. In contrast, young myopic adults revealed pseudomyopia of -0.5 D. Cycloplegic refraction should be performed in young hypermetropic adults complaining of various signs of asthenopia. PMID- 26686514 TI - DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G Parkinson's disease. AB - BACKGROUND: The objective of this study was to study motor and nonmotor symptoms and striatal dopaminergic denervation, as well as the relationship between them, in a cohort of asymptomatic relatives of patients with Parkinson's disease (PD) with the R1441G-leucine-rich repeat kinase 2 mutation. METHODS: Asymptomatic relatives of patients with PD and this mutation were tested for the presence of the mutation and evaluated for striatal, putamenal, and caudate dopaminergic transporters using (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3 fluoropropyl)-nortropane single-photon emission computed tomography binding ratios. Clinical and neuropsychological evaluations including timed motor tests, a smell identification test, and global cognition, attention, executive, visuospatial, and memory functions as well as depression, constipation, and rapid eye movement sleep behavior disorder were also assessed. RESULTS: Twenty-seven carriers and 19 noncarriers were studied. Compared with noncarriers, mutation carriers had significantly lower (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N (3-fluoropropyl)-nortropan mean striatal (P = 0.03), mean putamenal (P = 0.01), and lowest putamenal (P = 0.01) binding ratios. Multiple linear regression analysis showed that the carrier status and the execution of timed tests significantly predicted striatal (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N (3-fluoropropyl)-nortropane binding. The proportion of variation accounted for by the regression model of these variables was 69% for the putamen and 53% for the caudate nucleus. CONCLUSIONS: Asymptomatic carriers of the R1441G-leucine-rich repeat kinase 2 mutation have evidence of dopaminergic nigrostriatal denervation, mainly in the putamen, which is associated with a decline in the execution of complex motor tests. These tests could be early indicators of the ongoing dopaminergic deficit in this group at risk of PD. PMID- 26686515 TI - Lactic acid bacteria as a cell factory for riboflavin production. AB - Consumers are increasingly becoming aware of their health and nutritional requirements, and in this context, vitamins produced in situ by microbes may suit their needs and expectations. B groups vitamins are essential components of cellular metabolism and among them riboflavin is one of the vital vitamins required by bacteria, plants, animals and humans. Here, we focus on the importance of microbial production of riboflavin over chemical synthesis. In addition, genetic abilities for riboflavin biosynthesis by lactic acid bacteria are discussed. Genetically modified strains by employing genetic engineering and chemical analogues have been developed to enhance riboflavin production. The present review attempts to collect the currently available information on riboflavin production by microbes in general, while placing greater emphasis on food grade lactic acid bacteria and human gut commensals. For designing riboflavin-enriched functional foods, proper selection and exploitation of riboflavin-producing lactic acid bacteria is essential. Moreover, eliminating the in situ vitamin fortification step will decrease the cost of food production. PMID- 26686516 TI - Exposure to aflatoxin B1 in Thailand by consumption of brown and color rice. AB - This study assessed the aflatoxin B1 (AFB1) intake of the Thai population through consumption of contaminated brown and color rice. A total of 240 rice samples from two harvesting periods were collected in June/July 2012 (period I) and in December 2012/January 2013 (period II) and analyzed for AFB1 by HPLC with fluorescence detection (limit of detection (LOD) = 0.093 ng/g). Exposure assessment was based on AFB1 levels in rice and food intake data for rice according to Thai National Consumption. Frequency and levels of AFB1 were higher in period I (59%, >Cu2O>Cu>CuSO4>CuO for CBzs, and CuCl2?2H2O>>Cu2O>CuO>Cu>CuSO4 for PCBs. PMID- 26686524 TI - Rapid and direct electrochemical determination of Ni(II) in industrial discharge water. AB - Industrial water contains a number of contaminants, such as organic pollutants and heavy metals, which can significantly affect the quality of soil, ground and environmental waters. We have successfully optimized and tested an electrochemical method and sensor modified with dimethylglyoxime for monitoring of nickel(II). The detection limit was 0.03mg/L and determination limit was 0.09mg/L. Linear concentration range was observed from 0.06 to 0.5mg/L Ni(II) and it is suitable for the analysis of environmental waters. The effect of all parameters important for on-site measurements (such as interferences, presence of dissolved oxygen, temperature) was investigated and considered in the analysis of mine discharge water. Water samples were analyzed without any pretreatment or filtration. A low level of error (5.6%) was observed for analysis demonstrating the usability of the optimized sensor and method for on-site measurements. PMID- 26686526 TI - A Successful HSCT in a Girl with Novel LRBA Mutation with Refractory Celiac Disease. PMID- 26686525 TI - A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression. AB - Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1) bi-allelic mutations have been associated with syndromes of widespread congenital lymphatic dysplasia, including Hennekam Syndrome (HS). HS is characterized by lymphedema, lymphangiectasia, and intellectual disability. CCBE1 encodes a putative extracellular matrix protein but the HS-causing mutations have not been studied biochemically. We report two HS siblings, born to consanguineous parents of Turkish ancestry, whose clinical phenotype also includes protein losing enteropathy, painful relapsing chylous ascites, and hypogammaglobulinemia. We identified by whole exome and Sanger sequencing the homozygous CCBE1 C174Y mutation in both siblings. This mutation had been previously reported in another HS kindred from the Netherlands. In over-expression studies, we found increased intracellular expression of all forms (monomers, dimers, trimers) of the CCBE1 C174Y mutant protein, by Western blot, despite mutant mRNA levels similar to wild type (WT). In addition, we detected increased secretion of the mutant CCBE1 protein by ELISA. We further found the mutant and WT proteins to be evenly distributed in the cytoplasm, by immunofluorescence and confocal microscopy. Finally, we found a strong decrease of lymphatic vessels, with a corresponding diminished expression of CCBE1, by immunohistochemistry of the patients' intestinal biopsies. In contrast, mucosal blood vessels and muscularis mucosae showed normal CCBE1 staining. Our findings show that the mutant CCBE1 C174Y protein is not loss-of-function by loss-of-expression. PMID- 26686527 TI - Improvement of green tea polyphenol with milk on skin with respect to antioxidation in healthy adults: a double-blind placebo-controlled randomized crossover clinical trial. AB - Green tea polyphenols (GTP) have been widely tested for their effects on several metabolic syndromes and degenerative diseases such as cancer, cardiovascular diseases, and diabetes. The present study was formulated to assess the physiological efficacy of green tea polyphenol infused with milk (GTPM) on skin integrity in correlation with antioxidative status in healthy adults. Forty-four healthy voluntary subjects were recruited and assigned to two groups, who drank 240 ml of mineral water mixed with either an experimental (GTPM) or placebo package (2 packs per day) for the following 6 months. The experimental group then switched to the placebo package, and vice versa, for a further 6 months, with one month of washout period in between. During the initial, 3(rd), 6(th), 10(th), and 13(th) month anthropometric measurements were performed and fasting blood samples were withdrawn for various biochemical assays. Skin examination was performed at the initial, 6(th) and 13(th) month. No significant alterations were observed in any of the anthropometric measurements. Administration of GTPM significantly increased (p < 0.05) the antioxidant index and antioxidant enzyme activities when compared with the placebo group, whereas a concomitant decrease in the levels of lipid peroxidation were noted. Moreover, GTPM intake notably improved skin integrity and texture by markedly lowering (p < 0.05) skin wrinkles and roughness in elderly subjects. GTPM proved to be an effective antioxidant by lowering oxidative stress and thereby ameliorating skin texture and integrity. PMID- 26686528 TI - Longest follow-up of in situ working Bjork Shiley valve: 42-year follow-up. AB - The Bjork Shiley valve (BSV) is considered as the pioneer among modern disc valves, and eventually evolved into a reliable prosthesis after considerable research and multiple modifications. Various case reports have been published with follow-up of different types of BSV. We are reporting the longest follow-up ever published of a plano-convex type of BSV. Our patient's valve was implanted in 1973 due to a congenital bicuspid aortic valve with concomitant severe, symptomatic aortic stenosis, discovered at the age of 27. She presented with exertional dyspnoea, syncope and chest pain; however, her cardiovascular status remained stable and these symptoms abated after successful valve replacement at the age of 34. She is now 77 years old with no limitations in her activities and is able to walk a few miles most days of the week. Her echocardiograms throughout the decades have shown acceptable gradients across the aortic prosthesis without evidence of haemolysis. Our case report includes a summary of the patient with a discussion of the evidence that supports the durability of the original plano convex BSV. PMID- 26686529 TI - Voluntary Informed Consent in Paediatric Oncology Research. AB - In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research-care context. PMID- 26686530 TI - Keeping a target in memory does not increase the effect of the Muller-Lyer illusion on saccades. AB - The effects of visual contextual illusions on motor behaviour vary largely between experimental conditions. Whereas it has often been reported that the effects of illusions on pointing and grasping are largest when the movement is performed some time after the stimulus has disappeared, the effect of a delay has hardly been studied for saccadic eye movements. In this experiment, participants viewed a briefly presented Muller-Lyer illusion with a target at its endpoint and made a saccade to the remembered position of this target after a delay of 0, 0.6, 1.2 or 1.8 s. We found that horizontal saccade amplitudes were shorter for the perceptually shorter than for the perceptually longer configuration of the illusion. Most importantly, although the delay clearly affected saccade amplitude, resulting in shorter saccades for longer delays, the illusion effect did not depend on the duration of the delay. We argue that visually guided and memory-guided saccades are likely based on a common visual representation. PMID- 26686531 TI - Delayed grip relaxation and altered modulation of intracortical inhibition with aging. AB - Grip relaxation is a voluntary action that requires an increase in short-interval intracortical inhibition (SICI) in healthy young adults, rather than a simple termination of excitatory drive. The way aging affects this voluntary inhibitory action and timing of grip relaxation is currently unknown. The objective of this study was to examine aging-related delays in grip relaxation and SICI modulation for the flexor digitorum superficialis muscle during grip relaxation. The main finding was that young adults increased SICI to relax their grips, whereas older adults did not increase SICI with a prolonged grip relaxation time (p < 0.05 for both SICI modulation and grip relaxation time). A secondary experiment showed that both young and older adults did not change H reflex excitability during grip relaxation. Our data suggest that grip relaxation is mediated by increased cortical inhibitory output in young adults, and aging-related impairment in increasing cortical inhibitory output may hamper timely cessation of muscle activity. Our data also suggest a lesser role of the spinal circuits in grip muscle relaxation. This knowledge may contribute to understanding of aging related movement deterioration and development of interventions for improving modulation of SICI to improve muscle relaxation and movement coordination. PMID- 26686532 TI - Physician experiences and preferences in the treatment of HR+/HER2- metastatic breast cancer in the United States: a physician survey. AB - Sequential endocrine therapy (ET) is recommended for postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and without visceral symptoms. Chemotherapy (CT) can be considered after sequential ETs, but is associated with adverse side effects. We assessed physicians' preferences and self-reported prescribing patterns for ET and CT in the treatment of HR+/HER2- mBC at community practices in the United States. Community-based oncologists/hematologists from a nationwide online panel who treated postmenopausal women with HR+/HER2- mBC were invited to complete a survey, blinded to the identity of study sponsor. Treatment preferences were collected by treatment class of ET-based regimens versus CT and by agent for postmenopausal HR+/HER2- mBC patients after prior nonsteroidal aromatase inhibitor use in the adjuvant or mBC setting. Among 213 physicians who completed the survey, 78% were male, 71% were based in small/intermediate practices (2-9 oncologists/subspecialists), 55% had >10 years of experience, and 58% referred to the National Comprehensive Cancer Network Guidelines when treating mBC. Among first-line ETs, anastrozole was the most frequently used treatment (35%), followed by everolimus-based (EVE, 34%) and fulvestrant-based (FUL, 15%) therapy. After first-line ET, the most preferred second- and third line treatments were ET monotherapy (48% and 39%), ET combination therapy (31% and 19%), and CT monotherapy (13% and 30%). Comparing EVE versus FUL, physicians preferred EVE in all lines but first line. Efficacy was the most important consideration for treatment choice. Physicians prescribed CT in early lines mainly because of visceral symptoms. This survey of treatment patterns for HR+/HER2- mBC in community practice suggested that after first-line ET, ET mono- or combination therapy was commonly used for the second- and third-line treatments and CT monotherapy for third- or later line treatments. CTs were used in early lines for patients with visceral symptoms. PMID- 26686533 TI - Management of pediatric single-level vertebral hemangiomas presenting with myelopathy by three-pronged approach (ethanol embolization, laminectomy, and instrumentation): a single-institute experience. AB - PURPOSE: Pediatric vertebral hemangiomas (VH) are exceedingly rare benign and highly vascular tumours of the spine. There are no guidelines available for management of these patients in literature. Purpose of this study is to evaluate the role of intraoperative ethanol embolization, surgical decompression, and instrumented fusion in pediatric symptomatic VH with single-level involvement. METHODS: Surgery consisted of intraoperative bilateral pedicular absolute alcohol injection and laminectomy at the level of pathology followed by a short-/long segment instrumented fusion using pedicle screws and rod. Seven patients (mean age 14 +/- 2.4 years, range 10-17 years, five females and two males) (age < 18 years) who were treated using this technique at our institute since March 2008 to December 2013 were enrolled in this retrospective study. Demographical, clinical, radiological, operative details, and postoperative events were retrieved from hospital records. During follow-up visits, clinical status and imaging were recorded. Outcome assessed with clinical and neurological outcome score of American Spinal Injury Association (ASIA) Impairment Scale. RESULTS: Duration of symptoms ranged from 3 to 60 months (mean, 14.7 +/- 20.4 months). Clinical features include myelopathy with motor and sensory involvement in all (five were paraplegic), back pain in two patients, and bladder involvement in two patients. The preoperative American Spinal Injury Association (ASIA) Impairment Scale (AIS) were B in five patients and C and D in one patient each. All had pan vertebral body VH with severe cord compression in the thoracic region on imaging study. Mean duration of surgery was 248.6 +/- 60 minutes (range 195-310 min) and blood loss was 535 ml (range 200-1500 ml). Immediate embolization was achieved in all patients, which allowed laminectomy and soft tissue hemangioma removal relatively easy. Post surgery, at mean follow-up of 45.3 (+/-23.2) months (range 1-78 months), all patients showed improvement in power (sphincter improvement in two patients). ASIA were E in six patients and D in one patient at the last follow up. CONCLUSION: The present study is the largest series of pediatric symptomatic VH. This procedure is a safe, efficient method to treat symptomatic pediatric VH with severe cord compression. It seems to serve the purpose of providing embolization, cord decompression, rigid fusion at the same sitting without adding new morbidity, and preventing excessive blood loss. PMID- 26686534 TI - Epidermal growth factor receptor overexpression is common and not correlated to gene copy number in ependymoma. AB - PURPOSE: The aim of this study was to investigate the epidermal growth factor receptor (EGFR) status in ependymoma specimens, as there is a need for new prognostic and druggable targets in this disease. METHODS: Ependymomas (WHO grade II, n = 40; WHO grade III, n = 15) located spinal (n = 35), infratentorial (n = 14), and supratentorial (n = 6) of 53 patients with a median age of 40 (range, 2 79) years were analyzed for Ki-67, p53, and EGFR expression by immunohistochemistry using a tissue microarray and for EGFR gene copy number alterations/mutations. Results were correlated to clinical data. RESULTS: EGFR overexpression was found in 30/60% of ependymomas depending on the antibody used and was more pronounced in WHO grade III. High EGFR gene copy number gains were found in 6 (11%) ependymomas with half of them being amplifications. EGFR amplified ependymomas displayed an EGFR overexpression with both antibodies in two of three cases. A missense mutation in exon 20 of EGFR (S768I) was detected in one amplified case. CONCLUSIONS: EGFR is frequently overexpressed in ependymomas. Other mechanisms than amplification of the EGFR gene appear to contribute to EGFR overexpression in most cases. EGFR mutations may be present in a small subset of ependymomas. PMID- 26686535 TI - Why do patients participate in long-term cardiovascular trials?--a questionnaire based study. AB - INTRODUCTION: Participation in clinical trials by patients with cardiovascular disease is paramount to the development of new treatments. Capturing and keeping patients in the trials until the end is very important and trials are often of long duration and include patients in a clinically stable condition, with few symptoms and a low risk of recurrent disease. We investigated what motivates patients to participate in long-term cardiovascular trials. Increased knowledge may enhance inclusion and retention and minimize lost to follow-up or withdrawal of consent. MATERIALS AND METHODS: A questionnaire with 11 statements to elucidate the reasons for participation and retention in long-term clinical trials was used and replies from 135 participants in trials, 78% men, mean age was 68 years. RESULTS: The two most important reasons for participation were: "I am able to see the same doctor and nurse at the visits", indicated by 89 patients (66%), followed by "I want to promote science", which was indicated by 74 patients (55%). The least important reason was "The visits are free of cost". CONCLUSION: Patients who participate in cardiovascular clinical trials do so because it may provide access to more continuous care but equally important are altruistic motives including a wish to promote science. PMID- 26686545 TI - Multifocal abdominal splenosis. PMID- 26686546 TI - Predictive morphology, stoichiometry and structure of surface species in supported Ru nanoparticles under H2 and CO atmospheres from combined experimental and DFT studies. AB - Further understanding of the chemisorption properties towards CO and H2 on silica supported Ru nanoparticles is crucial in order to rationalize their high activity towards methanation, Fischer Tropsch and Water Gas Shift reactions. Ru nanoparticles having the same chemisorption properties towards CO and H2 were synthesized on different silica-based supports in order to combine various analytical techniques and obtain complimentary detailed information on their structure; while silica spheres were used in order to obtain high-resolution TEM images of the Ru nanoparticles, high surface area silica-based material (SBA) allowed CO chemisorption to be monitored by (13)C NMR spectroscopy. In addition, a model of the hcp-based Ru nanoparticles observed by HR-TEM was used to predict by ab initio calculations the CO and H2 coverages on the Ru nanoparticle under different conditions of interest in catalysis. For both adsorbates we show and quantify how the adsorption properties of the nanoparticle differ from the commonly used slab models. For the case of CO we show how the top, bridge and hollow sites can be present on the Ru nanoparticle, providing a description at atomistic level in good agreement with the IR spectroscopy measurements. PMID- 26686547 TI - Monitoring of Intracranial Pressure by CT-Defined Optic Nerve Sheath Diameter. AB - BACKGROUND AND PURPOSE: Intracranial pressure (ICP) can be monitored by the optic nerve sheath diameter (ONSD) technique. We hypothesized that diameter of the optic canal (OC) can be a limiting factor for this technique. METHODS: In the prospective cohort study, we analyzed CT scans of 600 OCs of healthy adults and 54 canals of patients with ICP monitoring. The diameters were measured through its length and the narrowest one was chosen for further analysis. ONSD was measured at 3 and 10 mm from the anterior opening of the canal. The correlation analysis was performed between invasive and ONSD methods of ICP monitoring and OC diameters in pathological cases. RESULTS: The narrowest cross-sectional area of the normal OC was 13.85+/-2.89 mm2 and varied from 25.5 to 6.6 mm2. Apparently 9.17% OCs were narrow (?10.9 mm2). Correlations exist between the optic nerve sheath area at the 3-mm distance from the anterior opening of the canal and the area of the anterior opening itself (P = .012), and the sheath area 10 mm from the anterior opening and the narrowest part of the canal (P = .015). Cases with narrow canals provided false-negative readings via ONSD method if compared with invasive monitoring. CONCLUSION: In its narrowest part, the average OC is 11 to 16.75 mm2 wide. We suggest measuring this area simultaneously with the ONSD during ICP monitoring. If the area of the narrowest lumen of the canal is less than 10 mm2, ONSD technique for ICP monitoring should not be used. PMID- 26686548 TI - Seroconversion for cytomegalovirus infection in a cohort of pregnant women in Quebec, 2010-2013. AB - Cytomegalovirus (CMV) is the leading cause of congenital infection and non genetic sensorineural hearing loss in children. There are no recent data on the incidence of CMV infection during pregnancy in Canada. This present study was undertaken to determine the seroprevalence of CMV IgG antibodies and the rate of seroconversion in a cohort of pregnant women in the province of Quebec, Canada. We used serum samples and questionnaire data collected as part of the 3D Pregnancy and Birth Cohort Study (2010-2013) conducted in Quebec, Canada. CMV IgG antibodies were determined in serum samples collected at the first and third trimesters. Associations between independent variables and seroprevalence were assessed using logistic regression, and associations with seroconversions, by Poisson regression. Of 1938 pregnant women tested, 40.4% were seropositive for CMV at baseline. Previous CMV infection was associated with: working as a daycare educator, lower education, lower income, having had children, first language other than French or English, and being born outside Canada or the United States. Of the 1122 initially seronegative women, 24 (2.1%) seroconverted between their first and third trimesters. The seroconversion rate was 1.4 [95% confidence interval (CI) 0.9-2.1]/10 000 person-days at risk or 3.9 (95% CI 2.5-5.9)/100 pregnancies (assuming a 280-day gestation). The high proportion of pregnant women susceptible to CMV infection (nearly 60%) and the subsequent rate of seroconversion are of concern. PMID- 26686549 TI - Interpersonal processes and self-injury: a qualitative study using Bricolage. AB - INTRODUCTION: Literature on self-injury has recognized the impact on the relationship between clients and staff. RATIONALE: There is an absence of a detailed account of interpersonal processes surrounding self-injury. AIM: A Bricolage qualitative research approach was carried out in the United Kingdom that explored the interpersonal processes surrounding self-injury. METHOD: Three pairs of clients and staff were interviewed about an incident of self-injury. The interviews were thematically analysed and then synthesized producing a deeper exploration of the relationship between the client and staff. FINDINGS: An interpersonal trigger followed by anger and shame, resulted in self-injury to 'numb' these experiences. DISCUSSION: Self-injury is conceptualized as a safety behaviour to avoid shame and anger and then as a maintenance cycle that traps the client in a reinforcing and rejecting relationship. Staff interviewed were able to reflect with the clients and help them reframe these experiences. IMPLICATIONS FOR PRACTICE: Mental Health Nurses can work with clients to understand their own interpersonal cycles of self-injury. They can then reflect on their own roles in this process and avoid reinforcing the clients' negative beliefs. WHAT THE STUDY ADDS TO INTERNATIONAL EVIDENCE: This is the first international paper to explore the interconnection between the client and a professional helper in their lived experiences of self-injury. PMID- 26686550 TI - On dissociating the neural time course of the processing of positive emotions. AB - Providing evidence for categorical theories of emotion mandates the inclusion of discrete emotion categories beyond the typical six "basic" emotions. Traditional neurophysiological investigations of emotion typically feature the six basic emotions with happiness as the lone positive exemplar. Here we studied how event related potentials (ERPs) might differentiate between two positive emotional expressions: happiness and pride, and if so, at what time interval. Furthermore, given divergent findings in the ERP literature with respect to viewing emotional expressions, we explicitly examined how task type modulates neurophysiological responses when the same stimuli are viewed. While a continuous electroencephalogram (EEG) was recorded, 20 healthy participants completed two tasks: an implicit task where participants judged whether or not a face featured a brown spot (freckle), and an explicit task where they judged the face as portraying a "happy," "proud," or "neutral" expression. Behavioral performance exceeded 90% accuracy on both tasks. In the explicit task, participants responded faster and more accurately for Happy compared to Proud and Neutral expressions. Neurophysiologically, amplitudes for N170, VPP and P250 ERPs differentiated emotional from neutral expressions, but not from each other. In contrast, the late SPW component significantly differentiated Happy and Proud expressions from each other. Moreover, main effects of Task were found for the VPP, P250, LPP and SPW; additionally, Emotion X Task interactions were observed for P250 and SPW. Our data stress that task demands may magnify or diminish neural processing differences between emotion categories, which therefore cannot be disentangled with a single experimental paradigm. Additionally, some ERP differences may also reflect variations in categorization difficulty. PMID- 26686551 TI - Predictability effect on N400 reflects the severity of reading comprehension deficits in aphasia. AB - Predictability effect on N400, in which low predictability words elicited a larger N400 than high predictability words did over central to posterior electrodes, has been used to index difficulty of lexical retrieval and semantic integration of words in sentence comprehension. This study examined predictability effect on N400 in aphasic patients to determine if the properties of N400 are suited to indexing the severity of reading comprehension deficits. Patients with aphasia were divided into high and low ability groups based on scores on the reading comprehension subtest in the Chinese Concise Aphasia Test (CCAT). The two aphasia groups, a group of healthy elders who were age-matched to the aphasic participants, and a group of young adults, were requested to read sentences that either ended with highly predictable words or unexpected but plausible words, while undergoing electroencephalography (EEG). The young adult and healthy elderly groups exhibited the typical centro-parietal distributed effect of predictability on N400; however, healthy elders exhibited a reduced N400 effect in a delayed time window compared to the young adults. Compared with the elderly control, the high ability aphasia group exhibited a comparable N400 effect in a more restricted time window; by contrast, the low ability aphasia group exhibited a frontal distributed N400 in a much later time window (400-700 ms). These data suggest that the severity of reading comprehension deficits affects predictability effect on a set of N400 characteristics (i.e., amplitude, time window, and topographic distribution), which may be effective as ERP signatures in the evaluation of language recovery in aphasia. PMID- 26686552 TI - Evidence for New Light-Independent Pathways for Generation of the Endogenous Aryl Hydrocarbon Receptor Agonist FICZ. AB - Activation of the aryl hydrocarbon receptor (AhR), a conserved transcription factor best known as a target for highly toxic halogenated substances such as dioxin, under normal xenobiotic-free conditions is of considerable scientific interest. We have demonstrated previously that a photoproduct of tryptophan, 6 formylindolo[3,2-b]carbazole (FICZ), fulfills the criteria for an endogenous ligand for this receptor and proposed that this compound is the enigmatic mediator of the physiological functions of AhR. Here, we describe novel light independent pathways by which FICZ can be formed. The oxidant H2O2 was shown to convert tryptophan to FICZ on its own in the absence of light. The enzymatic deamination of tryptamine yielded indole-3-acetaldehyde (I3A), which then rearranged to FICZ and its oxidation product, indolo[3,2-b]carbazole-6-carboxylic acid (CICZ). Indole-3-pyruvate (I3P) also produced I3A, FICZ, and CICZ. Malassezia yeast species, which constitute a part of the normal skin microbiota, produce a number of AhR activators from tryptophan. We identified both FICZ and CICZ among those products. Formation of FICZ from tryptophan or I3P produces a complex mixture of indole derivatives, some of which are CYP1A1 inhibitors. These can hinder the cellular clearance of FICZ and thereby increase its power as an AhR agonist. We present a general molecular mechanism involving dehydrogenations and oxidative coupling for the formation of FICZ in which I3A is the important precursor. In conclusion, our results suggest that FICZ is likely to be formed systemically. PMID- 26686554 TI - Supramolecular aggregates with distinct optical properties from PDI oligomers of similar structures. AB - The self-assembly behaviors of two series of monodispersed oligomers consisting of perylenediimide (PDI) linked by ethynylene and butadiynylene spacers are investigated in solutions. In spite of the very similar chemical structures, the two sets of oligomers manifest completely different optical properties upon self aggregation, implying differed aggregate structures. While the oligomers containing butadiynylene spacers form H-aggregates, those featuring ethynylene linkers display J-aggregation characteristics. Thermodynamic analysis revealed that the self-association constants of both series of oligomers increase with the number of PDI units in the backbones. Oligomers containing the same number of PDI units but different spacers display nearly identical enthalpy changes. According to the molecular exciton theory, the observed H- and J-aggregates are suggested to comprise similar packing motifs with slightly varied slipping angles, giving rise to greatly disparate optical properties. PMID- 26686553 TI - A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia. AB - Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment. PMID- 26686555 TI - [In Process Citation]. PMID- 26686556 TI - Affect and Motivation Are Critical in Constructive Meditation. PMID- 26686557 TI - Contact rate modulates foraging efficiency in leaf cutting ants. AB - Lane segregation is rarely observed in animals that move in bidirectional flows. Consequently, these animals generally experience a high rate of head-on collisions during their journeys. Although these collisions have a cost (each collision induces a delay resulting in a decrease of individual speed), they could also have a benefit by promoting information transfer between individuals. Here we explore the impact of head-on collisions in leaf-cutting ants moving on foraging trails by artificially decreasing the rate of head-on collisions between individuals. We show that head-on collisions do not influence the rate of recruitment in these ants but do influence foraging efficiency, i.e. the proportion of ants returning to the nest with a leaf fragment. Surprisingly, both unladen and laden ants returning to the nest participate in the modulation of foraging efficiency: foraging efficiency decreases when the rate of contacts with both nestbound laden or unladen ants decreases. These results suggest that outgoing ants are able to collect information from inbound ants even when these latter do not carry any leaf fragment and that this information can influence their foraging decisions when reaching the end of the trail. PMID- 26686558 TI - Preparation and applications of novel composites composed of metal-organic frameworks and two-dimensional materials. AB - Metal-organic frameworks (MOFs), an emerging type of porous crystalline materials, have received increasing attention in recent years due to their compositional, structural and chemical versatility. Moreover, great progress has been made in the fundamental study and technological development of two dimensional (2D) materials, such as graphene and metal dichalcogenide nanosheets, which exhibit a number of unique and attractive properties for wide applications. Recently, the smart integration of the aforementioned two types of functional materials, i.e. MOFs and 2D materials, has led to improved performance in molecular absorption, separation and storage, and shown promise in selective catalysis and biosensing. This feature article aims at providing a brief introduction to the composites composed of MOFs and 2D materials, focusing mainly on their preparation methods and applications. Finally, technical challenges and future opportunities in this field will also be discussed. PMID- 26686559 TI - Mechanistic modeling of ion-exchange process chromatography of charge variants of monoclonal antibody products. AB - Ion-exchange chromatography (IEX) is universally accepted as the optimal method for achieving process scale separation of charge variants of a monoclonal antibody (mAb) therapeutic. These variants are closely related to the product and a baseline separation is rarely achieved. The general practice is to fractionate the eluate from the IEX column, analyze the fractions and then pool the desired fractions to obtain the targeted composition of variants. This is, however, a very cumbersome and time consuming exercise. A mechanistic model that is capable of simulating the peak profile will be a much more elegant and effective way to make a decision on the pooling strategy. This paper proposes a mechanistic model, based on the general rate model, to predict elution peak profile for separation of the main product from its variants. The proposed approach uses inverse fit of process scale chromatogram for estimation of model parameters using the initial values that are obtained from theoretical correlations. The packed bed column has been modeled along with the chromatographic system consisting of the mixer, tubing and detectors as a series of dispersed plug flow and continuous stirred tank reactors. The model uses loading ranges starting at 25% to a maximum of 70% of the loading capacity and hence is applicable to process scale separations. Langmuir model has been extended to include the effects of salt concentration and temperature on the model parameters. The extended Langmuir model that has been proposed uses one less parameter than the SMA model and this results in a significant ease of estimating the model parameters from inverse fitting. The proposed model has been validated with experimental data and has been shown to successfully predict peak profile for a range of load capacities (15-28mg/mL), gradient lengths (10-30CV), bed heights (6-20cm), and for three different resins with good accuracy (as measured by estimation of residuals). The model has been also validated for a two component mixture consisting of the main mAb product and one of its basic charge variants. The proposed model can be used for optimization and control of preparative scale chromatography for separation of charge variants. PMID- 26686560 TI - Determination of organophosphate diesters in urine samples by a high-sensitivity method based on ultra high pressure liquid chromatography-triple quadrupole-mass spectrometry. AB - Organophosphate (OP) diesters in urine samples have potential use as biomarkers of organism exposure to environmentally relevant OP triester precursors and in particular OP triester flame retardants. This present study developed a quantitatively sensitive ultra high pressure liquid chromatography (UHPLC-MS) based method for urine and the determination of OP diesters (i.e. diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), bis(2-chloroisopropyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), di(2-ethylhexyl) phosphate (DEHP), bis(1-chloro-2-propyl) phosphate (BCIPP), and bis(2-butoxyethyl) phosphate (BBOEP)). Fortified with the 7 OP diesters, 1mL of human urine sample was cleaned up using weak anion exchange solid phase extraction and eluted with high ionic strength ammonium acetate buffer. Subsequently, 4 non-chlorinated OP diesters were directly determined using UHPLC-electrospray(-)-triple quadrupole MS (UHPLC-ESI(-)-QqQ-MS), and UHPLC-ESI(+)-QqQ-MS was used for determination of 3 chlorinated OP diesters after methylation using diazomethane. Recovery efficiencies of OP diesters ranged from 88 to 160% at three spiking levels (0.4, 2 and 10ng/mL urine). Matrix effects (MEs) and method limits of quantification (MLOQs) were 15-134% and 0.10-0.32ng/mL urine, respectively. Concentrations of OP diesters in n=12 urine samples (from 4 Canadian residents, 2014) varied as follows, nd-<0.28 (DNBP), nd-1.29 (DPHP), nd-<0.28 (DEHP), <0.16-12.33 (BCEP), nd 1.17 (BCDIPP) and nd-0.68ng/mL (BCIPP). PMID- 26686561 TI - Optimisation and establishment of separation conditions of organic acids from Usnea longissima Ach. by pH-zone-refining counter-current chromatography: Discussion of the eluotropic sequence. AB - The major bioactive constituents of Usnea longissima Ach. are organic acids. However, few recent literatures involve the preparative separation of these organic acids. In the present study, pH zone-refining counter-current chromatography is used to separate organic acids from crude sample of U. longissima Ach. The crude extract was separated with the two-phase solvent system Pet-EtAc-MeOH-H2O (5:5:3:7, v/v) with 10mM TFA in organic stationary phase and different concentration of the eluter in aqueous mobile phase for the screening of the most suitable separation conditions. From the crude extract (1.2g), 74.0mg of orsellinic acid at 92.7% purity, 55.5mg of 4-O-methylorsellinic acid at 97.7% purity, 353.5mg of evernic acid at 93.8% purity, 102.0mg of barbatic acid at 94.8% purity, 19.4 mg of diffractaic acid at 92.2% purity, and 44.9 mg of usnic acid at 95.7% purity were obtained using the selected conditions in which the concentration of TFA in stationary phase was 10mM and the concentration of NaOH in mobile phase was 10-20mM. The purities of the separated organic acids were measured by HPLC. And the data of electrospray ionization-liquid chromatography/mass spectrometry (ESI-LC/MS), (1)H NMR, and (13)C NMR were used for confirming chemical structures. PMID- 26686562 TI - In situ solvothermal growth of metal-organic framework-ionic liquid functionalized graphene nanocomposite for highly efficient enrichment of chloramphenicol and thiamphenicol. AB - Here we report a facile in situ solvothermal growth method for immobilization of metal-organic framework-ionic liquid functionalized graphene (MOF-5/ILG) composite on etched stainless steel wire. The X-ray diffraction spectra, scanning electron microscopy and transmission electron microscopy images showed that the metal organic framework possessed good crystal shape and its structure was not disturbed by the introduction of ILG. Moreover, the covalent bond established between the amino group of ILG and the carboxylic group of the metal organic framework improved the mechanical stability and structure uniformity of the microcrystals. The obtained material combined the favorable attributes of both metal-organic framework and ILG, having high surface area (820 m(2)/g) and good adsorption capability. Its adsorption properties were explored by preconcentrating chloramphenicol and thiamphenicol from aqueous solutions prior to gas chromatography-flame ionization detection. The MOF-5/ILG exhibited high enrichment capacity for the analytes as they could interact through pi-pi and H bonding interaction. Under the optimum conditions, good linearity (correlation coefficients higher than 0.9981), low limits of detection (14.8-19.5 ng/L), and good precision (relative standard deviations less than 6.0% (n=5)) were achieved. The MOF-5/ILG composite displayed durable property. The method was applied to the determination of two antibiotics in milk, honey, urine and serum samples with acceptable relative recoveries of 82.3-103.2%. PMID- 26686563 TI - Behavior of temporal parameters of the ground reactive forces for the walking of postmenopausal women. AB - The study aimed to examine the influence of body composition and menopause characteristics on certain temporal parameters of the behavior of vertical and anteroposterior components of ground reactive forces, as well as the vertical and anteroposterior rates on the walking of postmenopausal women. The sample consisted of 67 postmenopausal women, average age 59 years. Body composition was assessed by octapolar bioimpedance and ground reactive force by the Kistler force platform. Vertical loading rate correlated positively with age (r = 0.02) and negatively with weight (r = -0.33). The relationship between the rates of vertical loading and unloading associated positively with menopause time (r = 0.27) but negatively with weight (r = -0.27). Vertical unloading rate showed a negative association with abdominal visceral adiposity (r = -0.27). The relationship between the times of the intermediate and final phases of the support correlated significantly with abdominal visceral adiposity (r = 0.25) and fat mass (r = 0.24). The study suggests that fat mass and abdominal visceral adiposity affect the support time, and increased abdominal visceral adiposity implies a slower pre-suspension phase during the walking of postmenopausal women. Hormone replacement therapy was shown to be an enhancer of steeper vertical loading and anteroposterior unloading and longer time in the double support phase, indicating a greater stability of postmenopausal women when walking. PMID- 26686564 TI - Ecology of a key ecosystem engineer on hard coastal infrastructure and natural rocky shores. AB - The numbers of hard coastal artificial structures is increasing worldwide and there is now cumulative evidence that they support assemblages that are less diverse than natural shores. Here we investigated patterns of distribution and demography of the native barnacle Chthamalus stellatus on hard coastal structures and on natural rocky shores. Barnacles were 35% less abundant on hard structures regardless of substratum type (concrete or basalt). On a subset of sites we found that temporal population stability, growth and mortality were similar on natural rocky shores and hard structures. In contrast, barnacles were significantly larger and recruited more onto natural rocky shores. These results emphasise the important role of recruitment in determining the abundance of a key space occupier on hard coastal structures. Experimental work building on these results may generate insights that can be used as guidelines for the management of urbanised coastal areas. PMID- 26686565 TI - An Update on Nutrients and Blood Pressure. AB - Adverse blood pressure (BP) is a major independent risk factor for epidemic cardiovascular diseases affecting almost one-quarter of the adult population worldwide. Dietary intake is a major determinant in the development and progression of high BP. Lifestyle modifications, including recommended dietary guidelines, are advocated by the American Society of Hypertension, the International Society of Hypertension, the Japanese Society of Hypertension, and many other organisations for treating all hypertensive people, prior to initiating drug therapy and as an adjunct to medication in persons already on drug therapy. Lifestyle modification can also reduce high BP and prevent development of hypertension. This review synthesizes results from the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP), a cross-sectional epidemiological study of 4,680 men and women aged 40-59 years from Japan, the People's Republic of China, the United Kingdom, and the United States, published over the past few years on cross cultural BP differences. INTERMAP has previously reported that intakes of vegetable protein, glutamic acid, total and insoluble fibre, total polyunsaturated fatty acid and linoleic acid, total n-3 fatty acid and linolenic acid, phosphorus, calcium, magnesium, and non-heme iron were inversely related to BP. Direct associations of sugars (fructose, glucose, and sucrose) and sugar-sweetened beverages (especially combined with high sodium intake), cholesterol, glycine, alanine, and oleic acid from animal sources with BP were also reported by the INTERMAP Study. PMID- 26686566 TI - Emerging Burden of Cardiovascular Diseases in Bangladesh. AB - As a result of an epidemiological transition from communicable to non communicable diseases for last few decades, cardiovascular diseases (CVD) are being considered as an important cause of mortality and morbidity in many developing countries including Bangladesh. Performing an extensive literature search, we compiled, summarized, and categorized the existing information about CVD mortality and morbidity among different clusters of Bangladeshi population. The present review reports that the burden of CVD in terms of mortality and morbidity is on the rise in Bangladesh. Despite a few non-communicable disease prevention and control programs currently running in Bangladesh, there is an urgent need for well-coordinated national intervention strategies and public health actions to minimize the CVD burden in Bangladesh. As the main challenge for CVD control in a developing country is unavailability of adequate epidemiological data related to various CVD events, the present review attempted to accumulate such data in the current context of Bangladesh. This may be of interest to all stakeholder groups working for CVD prevention and control across the country and globe. PMID- 26686567 TI - Pharmacokinetics and Pharmacodynamics of Lomitapide in Japanese Subjects. AB - AIMS: Lomitapide is a licensed treatment for patients with homozygous familial hypercholesterolaemia in the USA, the EU, Canada, and Mexico. This study was conducted to compare the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of lomitapide between Japanese and Caucasian subjects with elevated low-density lipoprotein cholesterol (LDL-C) after single and multiple doses. METHODS: In this randomized, double-blind, placebo-controlled study, 36 Japanese and 36 Caucasian subjects with LDL-C levels >=110 mg/dL were administered an escalating lomitapide dose range of 10-60 mg or placebo. Subjects were assessed for safety, tolerability, and lipid levels. RESULTS: Exposure to lomitapide as measured by Cmax was linear and increased over the dose range of 10-60 mg for both single- and multiple-dose administration. The correlation between AUC0-t and Ctrough demonstrated the lack of differences in the PK of lomitapide among ethnic groups. Lomitapide dose-dependent reductions in lipid parameters were observed and showed no ethnic differences. The safety assessments showed that the main treatment-related side effects identified were increases in hepatic enzymes and that the majority of treatment-related treatment-emergent AEs were gastrointestinal disorders. CONCLUSIONS: Lomitapide was effective in reducing LDL C levels in a dose-dependent manner. Similar PK, efficacy, and safety profiles were observed in Japanese and Caucasian subjects, which suggest no differences in lomitapide activity or metabolism between the two populations compared in this study. PMID- 26686568 TI - PAI-1 in Myocardial Remodeling: Is Pharmacological Suppression by ARB Beneficial? PMID- 26686569 TI - Another Paradox Regarding Adiponectin Revisited. PMID- 26686570 TI - Clinical experience with the meningococcal B vaccine, Bexsero((r)): Prospects for reducing the burden of meningococcal serogroup B disease. AB - Although rare, invasive meningococcal disease remains an important cause of mortality and morbidity in children and young adults. Vaccines have been successfully introduced to help protect against meningococcal disease caused by serogroups A, C, W and Y, but until recently, a vaccine for serogroup B (MenB) was not available. In many industrialised countries, MenB causes the majority of meningococcal disease. Moreover, MenB outbreaks occur unpredictably, particularly in high-risk populations, such as university students. In 2013, Bexsero((r)) became the first broad-coverage vaccine to be licensed for active immunisation against MenB disease. Bexsero is now licensed in more than 35 countries worldwide for varying age groups, including the EU, Australia, Brazil, Canada, Chile, Uruguay and the USA. Clinical recommendations for the use of Bexsero have been published in several countries. Recommendations include use in high-risk groups, outbreak control and routine infant immunisation. Since initial licensure, considerable clinical experience has been gained. In Canada, 43,740 individuals received Bexsero during a vaccination programme in the Saguenay-Lac-Saint-Jean region of Quebec, where local disease incidence was high. In the USA, Bexsero was administered to >15,000 individuals during two college outbreaks prior to licensure, under an Investigational New Drug protocol. In the UK, the Joint Committee on Vaccination and Immunisation has recommended the inclusion of Bexsero in the routine immunisation schedule for infants. Publically funded vaccination programmes have been initiated in Italy, and there has been widespread use of the vaccine outside of publically reimbursed programmes. Overall, >1,000,000 doses of Bexsero have been distributed in 19 countries worldwide since 2013. The emerging clinical experience with Bexsero is consistent with findings from pre-licensure clinical studies, and no new safety concerns have been identified. Additional data on length of protection, potential impact on meningococcal carriage and transmission and strain coverage have also been published and will be reviewed. PMID- 26686571 TI - A behavioral economics intervention to increase pertussis vaccination among infant caregivers: A randomized feasibility trial. AB - OBJECTIVES: The incidence of pertussis has tripled in the past five years. Infants can be protected by "cocooning," or vaccinating household contacts with the Tdap vaccine. However, Tdap coverage for adult caregivers of infants is low. This study evaluated the feasibility and impact of interventions informed by behavioral economics (retail pharmacy vouchers for Tdap vaccines and a celebrity public service announcement) to increase Tdap vaccination among caregivers of young infants. METHODS: We conducted a randomized controlled feasibility trial among adults attending newborn well-child visits at an urban Philadelphia pediatric primary care clinic who were not previously vaccinated with Tdap. Participants were randomized to one of four conditions: ($5-off Tdap voucher vs. free voucher)*(watching a 1min video public service announcement (PSA) about Tdap vaccination vs. no PSA). Tdap vaccination was assessed by tracking voucher redemption and following up with participants by phone. RESULTS: Ninety-five adult caregivers of 74 infants were enrolled in the study (mean age 29.3 years; 61% male; relationship to newborn: 54% father, 33% mother, 13% grandparent or other; caregiver insurance status: 35% Medicaid, 34% private insurance, 32% uninsured). Only 1 subject redeemed the retail pharmacy Tdap voucher. Follow-up interviews suggest that, even with the voucher, significant barriers to vaccination remained including: delaying planned vaccination, perceived inconvenient pharmacy locations, and beliefs about pertussis risk and severity. CONCLUSIONS: Despite leveraging existing infrastructure for adult vaccination, results suggest that retail pharmacy vouchers delivered during a newborn visit are not an effective strategy for promoting Tdap. Alternate approaches are needed that prioritize convenience and provide an immediate opportunity to vaccinate when motivation is high. PMID- 26686572 TI - Glyceradehyde-3-phosphate dehydrogenase as a suitable vaccine candidate for protection against bacterial and parasitic diseases. AB - The enzyme glyceraldehyde-3-P-dehydrogenase (GAPDH) has been identified as having other properties in addition to its key role in glycolysis. The ability of GAPDH to bind to numerous extracellular matrices, modulation of host-immune responses, a role in virulence and surface location has prompted numerous investigators to postulate that GAPDH may be a good vaccine candidate for protection against numerous pathogens. Although immune responses against GAPDH have been described for many microorganisms, vaccines containing GAPDH have been successfully tested in few cases including those against the trematode-Schistosoma mansoni, the helminth-Enchinococcus multilocularis; the nematode filaria- Litomosoides sigmodontis; fish pathogens such as Aeromonas spp., Vibrio spp., Edwarsiella spp., and Streptococcus iniae; and environmental streptococci, namely, Streptococcus uberis and Streptococcus dysgalactiae. Before GAPDH-based vaccines are considered viable options for protection against numerous pathogens, we need to take into account the homology between the host and pathogen GAPDH proteins to prevent potential autoimmune reactions, thus protective GAPDH epitopes unique to the pathogen protein must be identified. PMID- 26686573 TI - Effect of Permanent Atrial Fibrillation on Cognitive Function in Patients With Chronic Heart Failure. AB - In patients with chronic heart failure (HF), cognitive impairment (CI) is associated with poorer treatment adherence and higher readmission and mortality rates. Previous studies suggest that atrial fibrillation (AF) could impair cognitive function. This study sought to assess the association between permanent AF (permAF) and CI in patients with HF. We evaluated cognitive function in 881 patients with stable HF (73 +/- 11 years, 44% women, 48% with preserved ejection fraction) using the Mini-Mental State Examination test (n = 876) and the Pfeiffer's Short Portable Mental Status Questionnaire (n = 848). CI was defined as a Mini-Mental State Examination score <24 or Short Portable Mental Status Questionnaire (errors) >2. The independent association between permAF and CI was assessed by binary logistic regression analysis. A total of 295 patients (33.5%) had CI, in 5.1% of cases moderate/severe. Patients with permAF had more frequently any degree of CI (43% vs 31%), and moderate/severe CI (8% vs 5%). In the multivariate analysis, CI was associated with permAF (odds ratio 1.54, 95% C.I. 1.05 to 2.28), an older age, female gender, diabetes mellitus, chronic kidney disease, previous stroke, New York Heart Association class III/IV, and lower systolic blood pressure. No interaction was found for AF and CI between patients with reduced and preserved ejection fraction. In conclusion, the presence of permAF is independently associated with CI in patients with HF, both with reduced and preserved ejection fraction. Given the clinical impact of CI in the HF population, active assessment of cognitive function is particularly warranted in patients with HF with permAF. PMID- 26686574 TI - Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K/Akt/Nrf2 pathway. AB - Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinalis and exerts anti-inflammatory, antioxidant, and anticarcinogenic activities in different cell types. It has been reported that CA is able to cause protective effects on experimental models of neurodegeneration. However, the exact mechanism by which CA prevents neuronal degeneration remains to be better studied. We investigated here whether there is a role for CA as a neuroprotective agent in a paraquat (PQ) model of Parkinson's disease (PD) regarding cellular and mitochondrial-related redox parameters. SH-SY5Y cells were treated with CA for 12h and were exposed to 100 MUM PQ for 24h. It was found that CA at different concentrations prevented the effects of PQ on cell viability and redox parameters. CA alleviated reactive oxygen and nitrogen species production elicited by PQ, as well as decreased the toxic effect on mitochondrial function. Inhibition of Pi3K/Akt pathway with LY294002 or silencing of Nrf2 expression partially blocked the reversal of redox impairment induced by CA. Therefore, CA activated Nrf2 through modulation of PI3K/Akt pathway resulting in increased levels of antioxidant enzymes and consequent neuroprotection. Thus, CA may be viewed as a potential neuroprotective agent to be used in cases of Parkinson's disease (PD). PMID- 26686575 TI - Atrazine and malathion shorten the maturation process of Xenopus laevis oocytes and have an adverse effect on early embryo development. AB - The use of pesticides has a negative impact on the environment. Amphibians have long been regarded as indicator species to pollutants due to their permeable skin and sensitivity to the environment. Studies have shown that population declines of some amphibians are directly linked with exposure to agricultural contaminants. In the past, much of the studies have focused on the toxic effect of contaminants on larvae (tadpoles), juvenile and adult frogs. However, due to the nature of their life cycle, amphibian eggs and early embryos are especially susceptible to the contaminants, and any alteration during the early reproductive stages may have a profound effect on the health and population of amphibians. In this study, we analyzed the effect of atrazine and malathion, two commonly used pesticides, on Xenopus laevis oocyte maturation and early embryogenesis. We found that both atrazine and malathion shortened the frog oocyte maturation process and resulted in reduced Emi2 levels at cytostatic factor-mediated metaphase arrest, and a high level of Emi2 is critically important for oocyte maturation. Furthermore, frog embryos fertilized under the influence of atrazine and/or malathion displayed a higher rate of abnormal division that eventually led to embryo death during early embryogenesis. PMID- 26686576 TI - Lignocellulose-based analytical devices: bamboo as an analytical platform for chemical detection. AB - This article describes the development of lignocellulose-based analytical devices (LADs) for rapid bioanalysis in low-resource settings. LADs are constructed using either a single lignocellulose or a hybrid design consisting of multiple types of lignocellulose. LADs are simple, low-cost, easy to use, provide rapid response, and do not require external instrumentation during operation. Here, we demonstrate the implementation of LADs for food and water safety (i.e., nitrite assay in hot-pot soup, bacterial detection in water, and resazurin assay in milk) and urinalysis (i.e., nitrite, urobilinogen, and pH assays in human urine). Notably, we created a unique approach using simple chemicals to achieve sensitivity similar to that of commercially available immunochromatographic strips that is low-cost, and provides on-site, rapid detection, for instance, of Eschericia coli (E. coli) in water. PMID- 26686577 TI - Combining antibody-drug conjugates and immune-mediated cancer therapy: What to expect? AB - Blockade of immune-checkpoints has emerged as one of the most promising approaches to improve the durability of anti-tumor responses in cancer patients. However, the fraction of patients experiencing durable responses to single agent immune checkpoint inhibitor treatment remains limited. Recent clinical reports suggest that patients responding best to checkpoint blockade therapies display higher levels of CD8(+) T-cells in the tumor prior to treatment. Therefore, combination treatments of immune-checkpoint inhibitors with compounds that increase the number of tumor infiltrating CD8(+) T cells may expand the therapeutic benefit of immuno-oncology (IO) drugs. Immunogenic cell death (ICD) of tumor cells is induced by certain classes of cytotoxic compounds and represents a potent stimulator of effector T-cell recruitment to tumors. In addition, several cytotoxics directly stimulate dendritic cell activation and maturation, resulting in improved anti-tumor immune responses when combined with IO compounds. Among them, several cytotoxic agents are currently utilized as payloads for antibody-drug conjugates (ADCs). Therefore, identification of optimal combination regimens between ADC- and IO compounds holds strong promise to overcome the current limitations of immune checkpoint inhibitors, by increasing the recruitment of CD8(+) effector T-cells to the tumor core. Here we review the emerging field of ADC/IO combination research, with a focus on how to optimally combine both modalities. The answer to this question may have a broader impact on oncology drug development, as synergistic activities between IO compounds and ADCs may increase the formation of tumor specific immunological memory, ultimately leading to durable responses in a larger fraction of cancer patients. PMID- 26686579 TI - Targeting transcription factors by small compounds--Current strategies and future implications. AB - Transcription factors are central regulators of gene expression and critically steer development, differentiation and death. Except for ligand-activated nuclear receptors, direct modulation of transcription factor function by small molecules is still widely regarded as "impossible". This "un-druggability" of non-ligand transcription factors is due to the fact that the interacting surface between transcription factor and DNA is huge and subject to significant changes during DNA-binding. Besides some "success studies" with compounds that directly interfere with DNA binding, drug targeting approaches mostly address protein protein interfaces with essential co-factors, transcription factor dimerization partners, chaperone proteins or proteins that regulate subcellular shuttling. An alternative strategy represent DNA-intercalating, alkylating or DNA-groove binding compounds that either block transcription factor-binding or change the 3D conformation of the consensus DNA-strand. Recently, much interest has been focused on chromatin reader proteins that steer the recruitment and activity of transcription factors to a gene transcription start site. Several small compounds demonstrate that these epigenetic reader proteins are exciting new drug targets for inhibiting lineage-specific transcription in cancer therapy. In this research update we will discuss recent advances in targeting transcription factors with small compounds, the challenges that are related to the complex function and regulation of these proteins and also the possible future directions and applications of transcription factor drug targeting. PMID- 26686578 TI - Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein. AB - P-glycoprotein (P-gp) is a member of the ATP-binding cassette transporter superfamily. This multidrug transporter utilizes energy from ATP hydrolysis for the efflux of a variety of hydrophobic and amphipathic compounds including anticancer drugs. Most of the substrates and modulators of P-gp stimulate its basal ATPase activity, although some inhibit it. The molecular mechanisms that are in play in either case are unknown. In this report, mutagenesis and molecular modeling studies of P-gp led to the identification of a pair of phenylalanine tyrosine structural motifs in the transmembrane region that mediate the inhibition of ATP hydrolysis by certain drugs (zosuquidar, elacridar and tariquidar), with high affinity (IC50's ranging from 10 to 30nM). Upon mutation of any of these residues, drugs that inhibit the ATPase activity of P-gp switch to stimulation of the activity. Molecular modeling revealed that the phenylalanine residues F978 and F728 interact with tyrosine residues Y953 and Y310, respectively, in an edge-to-face conformation, which orients the tyrosines in such a way that they establish hydrogen-bond contacts with the inhibitor. Biochemical investigations along with transport studies in intact cells showed that the inhibitors bind at a high affinity site to produce inhibition of ATP hydrolysis and transport function. Upon mutation, they bind at lower affinity sites, stimulating ATP hydrolysis and only poorly inhibiting transport. These results also reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. PMID- 26686580 TI - Inhibition of thioredoxin reductase by alantolactone prompts oxidative stress mediated apoptosis of HeLa cells. AB - The mammalian thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus, TrxR2 in mitochondria, and TrxR3 in testis, are essential seleno flavoenzymes with a conserved penultimate selenocysteine (Sec) residue at the C terminus, and have attracted increasing interests as potential targets for development of cancer chemotherapeutic agents. The sesquiterpene lactone alantolactone (ATL), an active component from the traditional folk medicine Inula helenium, has been documented possessing multiple pharmacological functions, especially the anticancer activity. However, the underlying mechanism has not been well defined. We reported that ATL inhibits both the recombinant TrxR and the enzyme in the cellular environment. The alpha-methylene-gamma-lactone moiety in ATL and the Sec residue in TrxR are critical for targeting TrxR by ATL. By employing our newly developed pull down assay, we demonstrated the remarkable elevation of the oxidized thioredoxin in HeLa cells after ATL treatment. In addition, ATL elicits accumulation of reactive oxygen species, and eventually induces apoptosis of HeLa cells. Importantly, overexpression of the functional TrxR attenuates the cytotoxicity of ATL, while knockdown of the enzyme sensitizes the cells to ATL treatment. Targeting TrxR thus discloses a novel molecular mechanism underlying the cellular action of ATL, and sheds light in considering the usage of ATL as a potential cancer chemotherapeutic agent. PMID- 26686582 TI - Workplace foodservice; perception of quality and trust. AB - In settings such as workplaces there is a growing acceptance that the food provided has a significant impact on health and wellbeing. This is a captive environment where the overall contribution of the meal served could be an important element of the overall diet and represents an under researched area. Despite growing demand, little information is available; time pressure when making food choice alongside the challenge of understanding information provided can act as barriers for healthy selection and can also decrease confidence in the food system. We would also argue that the fundamental human right of informing consumers what they are eating is not currently being addressed and is underscored. This study used focus groups to explore criteria that motivate peoples' food choice in a workplace foodservice setting. Thematic analysis was applied to categorise data according to frequently occurring responses. Data were collected from four focus groups in Germany and the UK with a total of 23 participants. Although there is little expectation in the quality of food served in the workplace, respondents valued any transparency of information and the opportunity to socialise with other work colleagues. Criteria of importance were identified as: Value for money, Variety, Naturalness, Nutrition, Portion Size, Taste, Visual Appearance, Origin, Animal welfare, Environmental impact, Fair Trade and Organic. Gaining insight into these criteria can enable operators to meet the needs and expectations of their customers in order to increase confidence in the food provided and in addition signpost a healthier selection. PMID- 26686583 TI - Factors influencing consumption of nutrient rich forest foods in rural Cameroon. AB - Studies show that a number of forest foods consumed in Cameroon are highly nutritious and rich in health boosting bioactive compounds. This study assessed the knowledge and perceptions towards the nutritional and health promoting properties of forest foods among forest dependent communities. The relationship between knowledge, perceptions and socio-demographic attributes on consumption of forest foods was also determined. A total of 279 females in charge of decision making with respect to food preparation were randomly selected from 12 villages in southern and eastern Cameroon and interviewed using researcher administered questionnaires. Multivariate logistic regression analysis was used to identify the factors affecting consumption of forest foods. Baillonella toxisperma (98%) and Irvingia gabonesis (81%) were the most known nutrient rich forest foods by the respondents. About 31% of the respondents were aware of the nutritional value and health benefits of forest foods. About 10%-61% of the respondents expressed positive attitudes to questions related with health benefits of specific forest foods. Consumption of forest foods was found to be higher among polygamous families and also positively related to length of stay in the forest area and age of respondent with consumption of forest foods. Education had an inverse relationship with use of forest foods. Knowledge and positive attitude towards the nutritional value of forest foods were also found to positively influence consumption of forest foods. Since knowledge was found to influence attitude and consumption, there is need to invest in awareness campaigns to strengthen the current knowledge levels among the study population. This should positively influence the attitudes and perceptions towards increased consumption of forest foods. PMID- 26686584 TI - Easy to open? Exploring the 'openability' of hospital food and beverage packaging by older adults. AB - Food is increasingly a packaged commodity, both in the community and in institutionalised settings such as hospitals, where many older people are malnourished. Previous research with patients aged over 65 years in NSW public hospitals identified difficulties opening milk, water, juices, cereal and tetra packs. The aim of this paper was to assess the ability of well older people living in the community to open food and beverage items routinely used in NSW hospitals in order to gain further insights into the older person/pack interaction and the role of hand and finger strength in pack opening. A sample of 40 older people in good health aged over 65 years from 3 community settings participated in the study. The attempts at pack opening were observed, the time taken to open the pack was measured and the correlation between grip and pinch strengths with opening times was determined. Tetra packs, water bottles, cereal, fruit cups, desserts, biscuits and cheese portions appeared to be the most difficult food products to open. Ten percent of the sample could not open the water bottles and 39% could not open cheese portions. The results were consistent with the previous research involving hospitalised older adults, adding emphasis to the conclusion that food and beverage packaging can be a potential barrier to adequate nutrition when particular types of packaged products are used in hospitals or the community. The ageing population is rapidly becoming a larger and more important group to consider in the provision of goods and services. Designers, manufacturers and providers of food and beverage products need to consider the needs and abilities of these older consumers to ensure good 'openability' and promote adequate nutritional intakes. PMID- 26686581 TI - Protein Arginine Methylation and Citrullination in Epigenetic Regulation. AB - The post-translational modification of arginine residues represents a key mechanism for the epigenetic control of gene expression. Aberrant levels of histone arginine modifications have been linked to the development of several diseases including cancer. In recent years, great progress has been made in understanding the physiological role of individual arginine modifications and their effects on chromatin function. The present review aims to summarize the structural and functional aspects of histone arginine modifying enzymes and their impact on gene transcription. We will discuss the potential for targeting these proteins with small molecules in a variety of disease states. PMID- 26686585 TI - In vitro and in vivo osteogenic activity of the novel vancomycin-loaded bone-like hydroxyapatite/poly(amino acid) scaffold. AB - BACKGROUND: Antibiotic-loaded carriers were developed because of their ability to fill cavities and deliver antibiotics locally following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate, has many shortcomings, such as heat production, non-bioresorbable and lack of bone regeneration or conduction. Bone-like hydroxyapatite/poly(amino acid) scaffolds have been shown to have controllable biodegradability, nontoxicity, some osteogenic and osteoconductive properties, which has great potential as a carrier for local delivery of antibiotics. Vancomycin-loaded bone-like hydroxyapatite/poly(amino acid) was successfully fabricated by a homogeneous method using a diffusion control system. In this study, bone regeneration using this scaffold was observed both in vitro and in vivo. METHODS: In vitro tests, MG63 cells were incubated with the vancomycin-loaded scaffold to observe its effects on the activation of osteoblasts. In vivo tests, the scaffolds were implanted into rabbit models of chronic osteomyelitis, including regular and methicillin-resistant Staphylococcus aureus. The effects were evaluated by gross observation, X-ray and histological observation. RESULTS: After incubating with the scaffold, MG63 cells exhibited good proliferative activity, and increased calcium and alkaline phosphatase synthesis compared with blank control group. In vivo tests, the experimental group showed increased bone growth in infectious bone defects compared with the control groups, regardless of the type of Staphylococcus aureus. CONCLUSION: Vancomycin-loaded bone-like hydroxyapatite/poly(amino acid) scaffold has good potential for the repair of infectious bone defects because of its ability to deliver antibiotics and promote bone regeneration. PMID- 26686586 TI - Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation. AB - Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/beta-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/beta-glycerolphosphate hydrogel showed that adding gelatin to chitosan/beta-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37C. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/beta glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/beta-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects. PMID- 26686587 TI - Nicotine impact on the structure of adult male guinea pig auditory cortex. AB - BACKGROUND: A growing body of evidence suggests that chronic cigarette smoking causes detrimental effects on brain morphology. AIM OF WORK: To study the structural changes in auditory cortex region (Layer V), under the influence of nicotine. MATERIAL AND METHODS: Three animal groups (10 each) were used; group I (control) and groups IIa and IIb received 3 and 6mg/kg nicotine respectively. The specimens from the auditory cortex were examined using light and electron microscopy and morphometry. RESULTS: Neurons and blood capillaries of the auditory cortex (layer V), were influenced by chronic nicotine treatment in a dose dependent manner. The neurons and their processes revealed disorganization and dissociation of microtubules. The neuronal cells nucleoli characteristically revealed large fibrillar centers detected by silver stain and ultrastructure. The blood capillaries revealed collapse, irregular lumen, thickened basal lamina, abnormal forms of nuclei and organization of microtubules. Neuroglia revealed marked reactivity. Morphometrically, there was a significant decrease in the thickness of the auditory cortex and the number of light neurons and a significant increase in the number of dark neurons in comparison to the control. CONCLUSION: Nicotine affects the integrity of the auditory cortex possibly by reducing metabolic and transcription activities. PMID- 26686588 TI - Cardiovascular pathology: looking back on the first 25 years and forward into the future. PMID- 26686589 TI - Induction of labour versus expectant management at term by subgroups of maternal age: an individual patient data meta-analysis. AB - BACKGROUND: British women are delaying childbirth. Women aged 35 years or over have a higher risk of perinatal death. There is a linear relationship between maternal age and delivery by emergency caesarean in nulliparous women. Many obstetricians induce older women at term attempting to improve perinatal outcomes, others are reluctant for fear of increasing caesarean rates. A recent systematic review of induction of labour versus expectant management in women at term, found induction was associated with a reduction in caesareans (OR 0.83, 95% CI 0.76-0.92). OBJECTIVES: To identify whether induction of labour changes the risk of caesarean section in women aged 35 years or over. STUDY DESIGN: SEARCH STRATEGY: Available data sets from RCTs included in the Wood et al. systematic review (31 trials) and suitable RCTs published since week 23, 2012. SELECTION CRITERIA: Studies were included if they were randomised controlled trials comparing induction of labour with expectant management at term with intact membranes with a singleton or multiple pregnancy in a cephalic presentation. DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis of individual patient data (IPD) using a random-effects model to calculate odds ratios. RESULTS: In total 2675 women (five studies) were included in the meta-analysis and 2526 women (four studies) were included in the IPD meta-analysis. There was no statistically significant increase in caesarean section rates seen in either analysis. CONCLUSIONS: Induction of labour in women of advanced maternal age has no statistically significant effect on caesarean section rates. PMID- 26686590 TI - Analysis of the gene polymorphism of aldosterone synthase (CYP11B2) and atrial natriuretic peptide (ANP) in women with preeclampsia. AB - OBJECTIVE: Preeclampsia (PE) is a major cause of mortality of mothers, fetuses and newborns around the world. The etiology of preeclampsia has not yet been clarified, but many studies indicate a multifactorial basis of PE. Aldosterone synthase (CYP11B2) is responsible for synthesis of aldosterone responsible for regulating blood pressure. Similarly, natriuretic peptide (ANP) regulates blood pressure through a variety of mechanisms affecting the sodium concentration and the amount of extracellular fluid. Currently, attention is paid to the role of the polymorphisms in the expression level of these genes. The aim of the study was to determine the frequencies of genotypes and alleles for polymorphisms of 344C>T CYP11B2 gene and 2238T>C ANP gene in women with preeclampsia and healthy pregnant women from the Caucasian population. STUDY DESIGN: The study included a group of 165 pregnant women (59 women with preeclampsia and 109 healthy pregnant women). DNA was extracted from peripheral blood. Determination of the polymorphism of -344C>T CYP11B2 gene and 2238T>C ANP gene was performed by PCR RFLP method. RESULTS: The results showed that the frequencies of the TC and CC genotypes of 2238T>C polymorphism in ANP gene were significantly higher in patients with PE compared to control group. For -344C>T polymorphism of CYP11B2 gene, the frequency of TT genotype was significantly higher in patients with hypertension than in controls (32.2% vs. 23.58%). CONCLUSIONS: Our findings showed that gene polymorphism of CYP11B2 (-344C>T) and ANP (2238T>C) may be associated with developing PE during pregnancy. PMID- 26686591 TI - Flexible DNA junction assisted efficient construction of stable gene nanoparticles for gene delivery. AB - A flexible DNA junction was designed to assist the construction of stable gene nanoparticles with multiple target gene copies, which can be used as efficient gene cargo with successful expression in eukaryotic cells for gene delivery. PMID- 26686592 TI - MCQ tests in Advanced Trauma Life Support (ATLS(c)): Development and revision. AB - BACKGROUND: In Advanced Trauma Life Support (ATLS(c)) courses, multiple choice question (MCQ) tests are used to assess student's post course knowledge. As part of the ninth Edition Revision Process, existing MCQ tests were reviewed and revised by an International MCQ Revision group. The aim of this study was to evaluate the revision procedure and its effects. METHODS: Based on psychometric data and evidence based guidelines for adequate MCQ item and test development, a detailed stepwise approach was determined and followed to evaluate the existing MCQs, and to guide test item revision or replacement. RESULTS: The MCQ Revision group composed three new draft test versions comprising of 40 MCQs each. These were beta-tested among ATLS Instructors in various countries involved in ATLS. Psychometric analysis demonstrated that a minority of MCQ items required revision to create three equally balanced tests. After these final adjustments, a new set of three validated MCQ tests was available for use in 9th edition ATLS provider courses. Beta testing was performed using instructors but not students. The failure rate amongst students of ATLS provider courses increased significantly after introduction of the new MCQ tests. CONCLUSION: ATLS tests were revised and updated using current evidence based guidelines and psychometric analysis. Difficulty of the tests was not initially beta-tested on students. Increasing test item discrimination and quality resulted in lower test scores by students. PMID- 26686593 TI - Preventable deaths and potentially preventable deaths. What are our errors? AB - BACKGROUND: A variety of systems have been applied to identify and address errors in the management of multiple trauma patients. This lack of standardisation represents a serious problem. OBJECTIVES: Detect preventable and potentially preventable deaths, and classify all the errors with universal language. METHODS: We studied all trauma patients over 16 admitted to the critical care unit or who died before. In multidisciplinary sessions we decided which deaths were preventable, potentially preventable and non preventable. Guided by ATLS protocols, we detected errors in their management that were classified using the taxonomy of Joint Commission. RESULTS: We registered 1236 trauma patients (ISS 20.77). Of the 115 trauma deaths, 19 were preventable or potentially preventable deaths. We recorded 130 errors in all deaths, 46 of them in preventable or potentially preventable deaths. Using our own classification, the main errors were delay in starting correct treatment or performance of CT in hemodynamically unstable patients. Using the taxonomy of Joint Commission, the main type error was clinical, during the intervention: the delay in initiating correct treatment. Mistakes were made in the emergency department by medical specialists. The incidence of therapeutic and diagnostic errors was similar. The main cause of error was human failure, specifically 'rule-based' errors CONCLUSIONS: Measuring and recording the results is the first step on the way to improving the quality of care for trauma patients. A common language like the taxonomy of Joint Commission will help standardise patient safety data, thus improving the recording of incidents and their analysis and treatment. PMID- 26686595 TI - The relationship between initial closed reduction and the surgical reconstruction of the radiocarpal joint line in distal radial fractures. AB - INTRODUCTION: Whilst initial closed reduction followed by definitive open fixation is widely applied in the treatment of distal radial fractures, the effect of the closed reduction on the reconstruction of the articular surface remains unclear. Our research questions were: METHODS: Palmar tilt and radiocarpal inclination of 425 patients were measured at admission, following initial closed reduction and after surgical reconstruction. RESULTS: Closed reduction increased palmar tilt by 12.1 degrees and radial inclination by 2.7 degrees . Open surgical reduction further corrected palmar tilt by 17.88 degrees and radial inclination by 3.5 degrees . Whilst there was no association between postoperative palmar tilt and initially achieved closed reduction, a significant association between radial inclination following closed reduction and surgical fixation was found. CONCLUSION: Our retrospective study challenges the existence of a relationship between the initial closed reduction and the reconstruction of the anatomic joint line in surgically treated distal radial fractures. PMID- 26686594 TI - Full circle: 3D femoral mapping demonstrates age-related changes that influence femoral implant positioning. AB - The geometry of the femur is important in the final position of an intramedullary implant; we hypothesised that the femoral geometry changes with age and this may predispose the elderly to anterior mal-positioning of these implants. We used CT DICOM data of 919 intact left femora and specialist software that allowed us to defined landmarks for measurement reference - such as the linea aspera - on a template bone that could be mapped automatically to the entire database. We found that older (>80 years) cortical bone is up to 1.5 mm thinner anteriorly and 2 mm thinner posteriorly than younger (<40 years) bone but the rate of change of posterior to anterior cortex thickness is greater in the older bone. We also found the isthmus in the elderly to be more distal and less substantial than in the younger bone. This study has demonstrated femoral geometry changes with age that may explain our perception that the elderly are at increased risk for anterior mal-positioning of intramedullary implants. PMID- 26686596 TI - The isolation and identification of Pantoea dispersa strain JFS as a non pathogenic surrogate for Salmonella Typhimurium phage type 42 in flour. AB - Salmonella is a common pathogen which has been the cause of foodborne illness outbreaks implicating a variety of commodities, including low-moisture foods such as flour. Salmonella costs more than any other pathogen in the United States in terms of health care expenses and time of lost work. Heat treatment can be used to reduce Salmonella and other pathogens in flour to safe levels. However, in low moisture foods, process times must be increased to achieve adequate lethality, possibly resulting in changes in the flour's functionality such as changes in the gluten quality, vitamin content, and the level of starch gelatinization. There is a need to determine the minimal heat treatment required to achieve desired lethality in flour and other low-moisture foods, with the goal of retaining the flour's functionality. Currently there is no published data about a nonpathogenic bacterial surrogate for Salmonella in flour. In this study, a surrogate, which closely matches the thermal death rate of Salmonella in flour, has been isolated. The surrogate was identified following an evaluation of thermal death curves of ten different strains of bacteria isolated from heat-treated flour and two nonpathogenic surrogates used in other commodities. Flour samples were inoculated with Salmonella or one of the twelve bacterial isolates, and then subjected to heat (70, 75, and 80 degrees C) for 12-60 min. The heat tolerance for each organism was determined by plating out at least four different time points for each temperature and comparing the death curve to those from Salmonella. The death curve from Pantoea dispersa was not statistically different (p<0.05) than the death curve of Salmonella. This strain of P. dispersa (strain JFS) can be used as a conservative, slightly more heat resistant, surrogate for Salmonella. It can be used to verify the combination of heat and time necessary to kill Salmonella in flour using a commercial heat-treatment process. PMID- 26686597 TI - Efficacy of oxidizing disinfectants at inactivating murine norovirus on ready-to eat foods. AB - Noroviruses are the leading cause of foodborne illness, and ready-to-eat foods are frequent vehicles of their transmission. Studies of the disinfection of fruits and vegetables are becoming numerous. It has been shown that strong oxidizing agents are more effective than other chemical disinfectants for inactivating enteric viruses. The aim of this study was to evaluate the efficacy of oxidizing disinfectants (sodium hypochlorite, chloride dioxide and peracetic acid) at inactivating noroviruses on fruits and vegetables, using a norovirus surrogate, namely murine norovirus 3, which replicates in cell culture. Based on plaque assay, solutions of peracetic acid (85 ppm) and chlorine dioxide (20 ppm) reduced the infectivity of the virus in suspension by at least 3 log10 units after 1 min, while sodium hypochlorite at 50 ppm produced a 2-log reduction. On the surface of blueberries, strawberries and lettuce, chlorine dioxide was less effective than peracetic acid and sodium hypochlorite, which reduced viral titers by approximately 4 logs. A surprising increase in the efficacy of sodium hypochlorite on surfaces fouled with artificial feces was noted. PMID- 26686598 TI - Thermal inactivation of Salmonella spp. in pork burger patties. AB - Predictive models, to estimate the reduction in Escherichia coli O157:H7 concentration in beef burgers, have been developed to inform risk management decisions; no analogous model exists for Salmonella spp. in pork burgers. In this study, "Extra Lean" and "Regular" fat pork minces were inoculated with Salmonella spp. (Salmonella 4,[5],12,i:-, Salmonella Senftenberg and Salmonella Typhimurium) and formed into pork burger patties. Patties were cooked on an electric skillet (to imitate home cooking) to one of seven internal temperatures (46, 49, 52, 55, 58, 61, 64 degrees C) and Salmonella enumerated. A generalised linear logistic regression model was used to develop a predictive model for the Salmonella concentration based on the internal endpoint temperature. It was estimated that in pork mince with a fat content of 6.1%, Salmonella survival will be decreased by -0.2407log10 CFU/g for a 1 degrees C increase in internal endpoint temperature, with a 5-log10 reduction in Salmonella concentration estimated to occur when the geometric centre temperature reaches 63 degrees C. The fat content influenced the rate of Salmonella inactivation (P=0.043), with Salmonella survival increasing as fat content increased, though this effect became negligible as the temperature approached 62 degrees C. Fat content increased the time required for patties to achieve a specified internal temperature (P=0.0106 and 0.0309 for linear and quadratic terms respectively), indicating that reduced fat pork mince may reduce the risk of salmonellosis from consumption of pork burgers. Salmonella serovar did not significantly affect the model intercepts (P=0.86) or slopes (P=0.10) of the fitted logistic curve. This predictive model can be applied to estimate the reduction in Salmonella in pork burgers after cooking to a specific endpoint temperature and hence to assess food safety risk. PMID- 26686599 TI - Dirty deeds and dirty bodies: Embodiment of the Macbeth effect is mapped topographically onto the somatosensory cortex. AB - The theory of embodied cognition claims that knowledge is represented in modal systems derived from perception. Recent behavioral studies found evidence for this hypothesis, for example, by linking moral purity with physical cleansing (the Macbeth effect). Neurophysiological approaches provided further support by showing an involvement of sensorimotor cortices for embodied metaphors. However, the exact role of this brain region for embodied cognitions remains to be cleared. Here we demonstrate that the involvement of the sensorimotor cortex for the embodied metaphor of moral-purity is somatotopically organized. Participants enacted in scenarios where they had to perform immoral or moral acts either with their mouths or their hands. Results showed that mouthwash products were particularly desirable after lying in a voice mail and hand wash products were particularly desirable after writing a lie, thus demonstrating that the moral purity metaphor is specific to the sensorimotor modality involved in earlier immoral behavior. FMRI results of this interaction showed activation in sensorimotor cortices during the evaluation phase that was somatotopically organized with respect to preceding lying in a voice mail (mouth-area) or in a written note (hand-area). Thus, the results provide evidence for a central role of the sensorimotor cortices for embodied metaphors. PMID- 26686600 TI - Clinical and allelic heterogeneity in a pediatric cohort of 11 patients carrying MFN2 mutation. AB - INTRODUCTION: The Mitofusin 2 gene (MFN2), which encodes a mitochondrial membrane protein, is known to be the first cause of autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2) with early onset. This gene is involved in typical CMT2A and in more atypical phenotypes as optic atrophy or spastic paraplegia. CMT2 refers to inherited axonal polyneuropathy, which associates progressive peripheral motor and sensory neuropathy, a family history consistent mainly with autosomal dominant inheritance, and normal nerve conduction velocities. SUBJECTS: Between 1999 and 2012, the genetic diagnosis of MFN2 mutation was made in 11 children who were treated in our department for different neurological symptoms. All data including family and personal history data, results of standardized clinical and electrophysiology testing, brain magnetic resonance imaging (MRI), neuro-ophthalmic evaluation, muscle biopsy histopathology and molecular diagnosis were retrospectively analyzed. RESULTS: Five different mutations were found in 6 unrelated families. Three of them have previously been described; the two remaining are new mutations: one of them related a new phenotype. Clinical signs appeared before the age of 6 years in more than half of the patients (54%). The motor deficit was predominant in 8 patients (72%). Two children presented an acute onset of disease that stabilized afterwards; the other children showed a more progressive deterioration that was managed symptomatically. CONCLUSION: This large pediatric study describes a great interfamilial and intrafamilial phenotypic variability. We recommend screening this gene in pediatric patient with chronic neurologic symptoms such as motor deficit or optic atrophy but also in acute neurologic deficiencies such as subacute polyradiculoneuritis. PMID- 26686601 TI - Surgical versus medical treatment for children with epileptic encephalopathy in infancy and early childhood: Results of an international multicenter cohort study in Far-East Asia (the FACE study). AB - OBJECTIVE: To compare the seizure and developmental outcomes in infants and young children with epileptic encephalopathy who have undergone surgical and medical treatments. METHODS: An international, multicenter, observational cohort study was undertaken. A total of 317 children aged <6 years, who had frequent disabling seizures despite intensive medical treatments, were registered. Among the enrolled children, 250 were treated medically (medical group), 31 underwent resective surgery (resective group), and 36 underwent palliative surgery [callosotomy (n=30) or vagal nerve stimulation (n=6); palliative group] on admission. Seizure and developmental outcomes were obtained for 230 children during the 3-year follow-up period. Cox proportional hazard model was used to adjust for clinical backgrounds among treatment groups when comparing the seizure free survival rates. RESULTS: At the 3-year follow-up, seizure-free survival was 15.7%, 32.1%, and 52.4% in the medical, palliative, and resective groups, respectively. The adjusted hazard ratios for seizure recurrence in the resective and palliative groups versus the medical group were 0.43 (95% CI, 0.21-0.87, P=0.019) and 0.82 (95% CI, 0.46-1.46, P=0.50), respectively; the former was statistically significant. Regarding the developmental outcome, the mean DQs in the resective group increased significantly compared to those in the medical group during the follow-up (P<0.01). As for subgroup analysis, better seizure and development outcomes were demonstrated in the resective group compared to the medical group in children with nonsyndromic epilepsies (those to which no known epilepsy syndromes were applicable). SIGNIFICANCE: These results suggest that surgical treatments, particularly resective surgeries, are associated with better seizure and developmental outcomes compared with successive medical treatment. The present observations may facilitate the identification of infants and young children with epileptic encephalopathy who could benefit from surgery. PMID- 26686602 TI - T11 vertebra fracture in ankylosing spondylitis after minor trauma. PMID- 26686603 TI - Concomitant epidural and subdural spinal abscess: a case report. AB - BACKGROUND CONTEXT: Spinal subdural abscess (SSA) is a rare occurrence for which the management typically involves open surgical removal and washout. PURPOSE: This case report aims to review the literature and discuss the management of patients with SSA. STUDY DESIGN: We present a case of a 33-year-old female who presented with a spinal epidural abscess and concurrent SSA. She presented in the context of intravenous (IV) drug use, back pain, and generalized lower extremity weakness. METHODS: The literature was reviewed with a focus on modern treatment options for SSA. Our patient was managed with IV antibiotics, and separate laminectomies and washouts for both lesions. RESULTS: The patient recovered well with return of neurologic function and normalization of infection markers. The review of the literature resulted in a management flowchart that will help direct treatment of SSA. CONCLUSIONS: The literature suggests that in a patient with a definitive diagnosis of SSA, limited surgical management and IV antibiotics are the mainstay of treatment in a patient with a decline in neurologic function. There may be a role for expectant management in the absence of diagnostic imaging or the neurologically stable patient. PMID- 26686604 TI - Patient and surgeon radiation exposure during spinal instrumentation using intraoperative computed tomography-based navigation. AB - BACKGROUND CONTEXT: Imaging modalities used to visualize spinal anatomy intraoperatively include X-ray studies, fluoroscopy, and computed tomography (CT). All of these emit ionizing radiation. PURPOSE: Radiation emitted to the patient and the surgical team when performing surgeries using intraoperative CT based spine navigation was compared. STUDY DESIGN/SETTING: This is a retrospective cohort case-control study. PATIENT SAMPLE: Seventy-three patients underwent CT-navigated spinal instrumentation and 73 matched controls underwent spinal instrumentation with conventional fluoroscopy. OUTCOME MEASURES: Effective doses of radiation to the patient when the surgical team was inside and outside of the room were analyzed. The number of postoperative imaging investigations between navigated and non-navigated cases was compared. METHODS: Intraoperative X ray imaging, fluoroscopy, and CT dosages were recorded and standardized to effective doses. The number of postoperative imaging investigations was compared with the matched cohort of surgical cases. A literature review identified historical radiation exposure values for fluoroscopic-guided spinal instrumentation. RESULTS: The 73 navigated operations involved an average of 5.44 levels of instrumentation. Thoracic and lumbar instrumentations had higher radiation emission from all modalities (CT, X-ray imaging, and fluoroscopy) compared with cervical cases (6.93 millisievert [mSv] vs. 2.34 mSv). Major deformity and degenerative cases involved more radiation emission than trauma or oncology cases (7.05 mSv vs. 4.20 mSv). On average, the total radiation dose to the patient was 8.7 times more than the radiation emitted when the surgical team was inside the operating room. Total radiation exposure to the patient was 2.77 times the values reported in the literature for thoracolumbar instrumentations performed without navigation. In comparison, the radiation emitted to the patient when the surgical team was inside the operating room was 2.50 lower than non navigated thoracolumbar instrumentations. The average total radiation exposure to the patient was 5.69 mSv, a value less than a single routine lumbar CT scan (7.5 mSv). The average radiation exposure to the patient in the present study was approximately one quarter the recommended annual occupational radiation exposure. Navigation did not reduce the number of postoperative X-rays or CT scans obtained. CONCLUSIONS: Intraoperative CT navigation increases the radiation exposure to the patient and reduces the radiation exposure to the surgeon when compared with values reported in the literature. Intraoperative CT navigation improves the accuracy of spine instrumentation with acceptable patient radiation exposure and reduced surgical team exposure. Surgeons should be aware of the implications of radiation exposure to both the patient and the surgical team when using intraoperative CT navigation. PMID- 26686606 TI - An unusual cause of dysphagia: a cervical epidural abscess. PMID- 26686605 TI - Risk factors for surgical site infection after posterior cervical spine surgery: an analysis of 5,441 patients from the ACS NSQIP 2005-2012. AB - BACKGROUND CONTEXT: The incidence of surgical site infection (SSI) following posterior cervical surgery has been reported as high as 18% in the literature. Few large studies have specifically examined posterior cervical procedures. PURPOSE: The study aims to examine the incidence, timing, and risk factors for SSI following posterior cervical surgery. DESIGN: This is a retrospective cohort study of prospectively collected data in a national surgical outcomes database. PATIENT SAMPLE: The sample includes patients who underwent posterior cervical spine surgery between 2005 and 2012 identified in the American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Data File. OUTCOME MEASURES: The 30-day rate of postoperative SSI, timing of diagnosis, and associated risk factors were determined. METHODS: The ACS NSQIP was used to identify 5,441 patients who underwent posterior cervical spine surgery by Current Procedural Terminology codes from 2005 to 2012. Thirty-day readmission data were obtained for 2011-2012. The incidence and timing of SSI were determined. Multivariable logistic regression analysis was then performed to identify significant risk factors. RESULTS: Of the 5,441 patients identified as having undergone posterior cervical surgery, 3,724 had a posterior cervical decompression, 1,310 had a posterior cervical fusion, and 407 underwent cervical laminoplasty. Surgical site infection within 30 days was identified in 160 patients (2.94%), with 80 of those cases being superficial SSI. There was no significant difference in SSI rate among the three procedure groups. The average time for diagnosis of SSI was over 2 weeks. In 2011-2012, 36.9% of patients with SSI were readmitted within 30 days. Several significant predictors of SSI were identified in univariate analysis, including body mass index (BMI) >35, chronic steroid use, albumin <3, hematocrit <33, platelets <100, higher American Society of Anesthesiologists class, longer operative time, and longer hospital admission. Independent risk factors, including BMI >35 (odds ratio [OR]=1.78, p=.003), chronic steroid use (OR=1.73, p=.049), and operative time >197 minutes (OR=2.08, p=.005), were identified in multivariable analysis. CONCLUSIONS: Optimization of preoperative nutritional status, serum blood cell counts, and operative efficiency may lead to a reduction in SSI rates. Obese patients and patients on chronic steroid therapy should be counseled on elevated SSI risk. PMID- 26686607 TI - In silico modelling of prostacyclin and other lipid mediators to nuclear receptors reveal novel thyroid hormone receptor antagonist properties. AB - Prostacyclin (PGI2) is a key mediator involved in cardiovascular homeostasis, acting predominantly on two receptor types; cell surface IP receptor and cytosolic peroxisome proliferator activated receptor (PPAR) beta/delta. Having a very short half-life, direct methods to determine its long term effects on cells is difficult, and little is known of its interactions with nuclear receptors. Here we used computational chemistry methods to investigate the potential for PGI2, beraprost (IP receptor agonist), and GW0742 (PPARbeta/delta agonist), to bind to nuclear receptors, confirmed with pharmacological methods. In silico screening predicted that PGI2, beraprost, and GW0742 have the potential to bind to different nuclear receptors, in particular thyroid hormone beta receptor (TRbeta) and thyroid hormone alpha receptor (TRalpha). Docking analysis predicts a binding profile to residues thought to have allosteric control on the TR ligand binding site. Luciferase reporter assays confirmed that beraprost and GW0742 display TRbeta and TRalpha antagonistic properties; beraprost IC50 6.3 * 10( 5)mol/L and GW0742 IC50 4.9 * 10(-6) mol/L. Changes to triiodothyronine (T3) induced vasodilation of rat mesenteric arteries measured on the wire myograph were measured in the presence of the TR antagonist MLS000389544 (10(-5) mol/L), beraprost (10(-5) mol/L) and GW0742 (10(-5) mol/L); all significantly inhibited T3 induced vasodilation compared to controls. We have shown that both beraprost and GW0742 exhibit TRbeta and TRalpha antagonist behaviour, and suggests that PGI2 has the ability to affect the long term function of cells through binding to and inactivating thyroid hormone receptors. PMID- 26686608 TI - Residue mutations of xylanase in Aspergillus kawachii alter its optimum pH. AB - Aspergillus kawachii and Aspergillus niger have been traditionally used as molds for commercial microbial fermentation because of their capability to grow in extremely acidic environments and produce acid-stable enzymes. Endo-1,4-beta xylanase cleaves the glycosidic bonds in the xylan backbone, consequently reducing the degree of polymerization of the substrate. The amino acid sequences of xylanases from A. kawachii and A. niger only differ in one amino acid residue. However, the xylanases from A. kawachii and A. niger show different optimum pH values of 2.0 and 3.0, respectively. In this study, we synthesized the A. kawachii xylanase gene (XynC) on the basis of the bias codon of yeast and mutated the gene in the dominating region related to optimum pH shifting during gene synthesis. After the overexpression of this gene in Pichia pastoris G115, the mutant (Thr64Ser) enzyme (XynC-C) showed an optimum pH of 3.8, which indicated partial alkalinity compared with the original xylanase from A. kawachii. Similar to that of the enzyme with one residue mutation (Asp48Asn), the optimum pH of the enzyme with two residue mutations (Thr64Ser and Asp48Asn) shifted to 5.0. The result indicated that mutation Asp48 was more important than mutation Thr64 in optimum pH shifting. We proposed a model that explains the lower optimum pH of XynC-C than other members of the xylanase family G. XynC-C showed similar proteolytic resistance and Km and Vmax values for beechwood xylan to other xylanases. PMID- 26686609 TI - Mycosynthesis of silver and gold nanoparticles: Optimization, characterization and antimicrobial activity against human pathogens. AB - This study was aimed to isolate soil fungi from Kolli and Yercaud Hills, South India with the ultimate objective of producing antimicrobial nanoparticles. Among 65 fungi tested, the isolate, Bios PTK 6 extracellularly synthesized both silver and gold nanoparticles with good monodispersity. Under optimized reaction conditions, the strain Bios PTK 6 identified as Aspergillus terreus has produced extremely stable nanoparticles within 12h. These nanoparticles were characterized by UV-vis. spectrophotometer, HR-TEM, FTIR, XRD, EDX, SAED, ICP-AES and Zetasizer analyses. A. terreus synthesized 8-20 nm sized, spherical shaped silver nanoparticles whereas gold nanoparticles showed many interesting morphologies with a size of 10-50 nm. The presence and binding of proteins with nanoparticles was confirmed by FTIR study. Interestingly, the myco derived silver nanoparticles exhibited superior antimicrobial activity than the standard antibiotic, streptomycin except against Staphylococcus aureus and Bacillus subtilis. The leakage of intracellular components such as protein and nucleic acid demonstrated that silver nanoparticles damage the bacterial cells by formation of pores, which affects membrane permeability and finally leads to cell death. Further, presence of nanoparticles in the bacterial membrane and the breakage of cell wall were also observed using SEM. Thus, the obtained results clearly reveal that these antimicrobial nanoparticles could be explored as promising candidates for a variety of biomedical and pharmaceutical applications. PMID- 26686610 TI - Characterization of bacterial diversity associated with calcareous deposits and drip-waters, and isolation of calcifying bacteria from two Colombian mines. AB - Bacterial carbonate precipitation has implications in geological processes and important biotechnological applications. Bacteria capable of precipitating carbonates have been isolated from different calcium carbonate deposits (speleothems) in caves, soil, freshwater and seawater around the world. However, the diversity of bacteria from calcareous deposits in Colombia, and their ability to precipitate carbonates, remains unknown. In this study, conventional microbiological methods and molecular tools, such as temporal temperature gradient electrophoresis (TTGE), were used to assess the composition of bacterial communities associated with carbonate deposits and drip-waters from two Colombian mines. A genetic analysis of these bacterial communities revealed a similar level of diversity, based on the number of bands detected using TTGE. The dominant phylogenetic affiliations of the bacteria, determined using 16S rRNA gene sequencing, were grouped into two phyla: Proteobacteria and Firmicutes. Within these phyla, seven genera were capable of precipitating calcium carbonates: Lysinibacillus, Bacillus, Strenotophomonas, Brevibacillus, Methylobacterium, Aeromicrobium and Acinetobacter. FTIR and SEM/EDX were used to analyze calcium carbonate crystals produced by isolated Acinetobacter gyllenbergii. The results showed that rhombohedral and angular calcite crystals with sizes of 90MUm were precipitated. This research provides information regarding the presence of complex bacterial communities in secondary carbonate deposits from mines and their ability to precipitate calcium carbonate from calcareous deposits of Colombian mines. PMID- 26686611 TI - Antagonistic effects of Bacillus subtilis subsp. subtilis and B. amyloliquefaciens against Macrophomina phaseolina: SEM study of fungal changes and UV-MALDI-TOF MS analysis of their bioactive compounds. AB - The antifungal effect of Bacillus subtilis subsp. subtilis PGPMori7 and Bacillus amyloliquefaciens PGPBacCA1 was evaluated against Macrophomina phaseolina (Tassi) Goid. Cell suspension (CS), cell-free supernatant (CFS) and the lipopeptide fraction (LF) of PGPMori7 and PGPBacCA1 were screened against three different M. phaseolina strains. CS exhibited the highest inhibitory effect (around 50%) when compared to those of CFS and LF, regardless of the fungal strain studied. The synthesis of lipopeptides was studied by UV-MALDI TOF. Chemical analysis of Bacillus metabolite synthesis revealed that surfactin and iturin were mainly produced in liquid medium. Potential fengycin was also co-produced when both Bacillus were cultivated in solid medium. In co-culture assays, the bacterial colony-fungal mycelium interface at the inhibition zone was evaluated by both scanning electron microscopy (SEM) and UV-MALDI TOF, the former to determine the structural changes on M. phaseolina cells and the latter to identify the main bioactive molecules involved in the inhibitory effect. PGPBacCA1 produced surfactin, iturin and fengycin in the inhibition zone while PGPMori7 only produced these metabolites within its colony and not in the narrow inhibition zone. Interestingly, SEM revealed that PGPBacCA1 induced damage in M. phaseolina sclerotia, generating a fungicidal effect as no growth was observed when normal growth conditions were reestablished. In turn, PGPMori7 inhibited the growth of the Macrophomina mycelium without fungal injury, resulting only in a fungistatic activity. From these results, it was determined that the two bacilli significantly inhibited the growth of an important phytopathogenic fungus by at least two different mechanisms: lipopeptide synthesis and competition among microorganisms. PMID- 26686612 TI - Agrobacterium tumefaciens-mediated transformation: An efficient tool for insertional mutagenesis and targeted gene disruption in Harpophora oryzae. AB - The endophytic filamentous fungus Harpophora oryzae is a beneficial endosymbiont isolated from the wild rice. H. oryzae could not only effectively improve growth rate and biomass yield of rice crops, but also induce systemic resistance against the rice blast fungus, Magnaporthe oryzae. In this study, Agrobacterium tumefaciens-mediated transformation (ATMT) was employed and optimized to modify the H. oryzae genes by either random DNA fragment integration or targeted gene replacement. Our results showed that co-cultivation of H. oryzae conidia with A. tumefaciens in the presence of acetosyringone for 48 h at 22 degrees C could lead to a relatively highest frequency of transformation, and 200 MUM acetosyringone (AS) pre-cultivation of A. tumefaciens is also suggested. ATMT mediated knockout mutagenesis was accomplished with the gene-deletion cassettes using a yeast homologous recombination method with a yeast-Escherichia Agrobacterium shuttle vector pKOHo. Using the ATMT-mediated knockout mutagenesis, we successfully deleted three genes of H. oryzae (HoATG5, HoATG7, and HoATG8), and then got the null mutants DeltaHoatg5, DeltaHoatg7, and DeltaHoatg8. These results suggest that ATMT is an efficient tool for gene modification including randomly insertional mutagenesis and gene deletion mutagenesis in H. oryzae. PMID- 26686613 TI - Characterization of an extracellular biofunctional alginate lyase from marine Microbulbifer sp. ALW1 and antioxidant activity of enzymatic hydrolysates. AB - A novel alginate-degrading marine bacterium Microbulbifer sp. ALW1 was isolated from rotten brown alga. An extracellular alginate lyase was purified to electrophoretic homogeneity and had a molecular mass of about 26.0 kDa determined by SDS-PAGE and size exclusion chromatography. This enzyme showed activities towards both polyguluronate and polymannuronate indicating its bifunctionality while with preference for the former substrate. Using sodium alginate as a substrate, strain ALW1 alginate lyase was optimally active at 45 degrees C and pH 7.0. It was stable at 25 degrees C, 30 degrees C, 35 degrees C and 40 degrees C, but not stable at 50 degrees C. This alginate lyase showed good stability over a broad pH range (5.0-9.0). The enzyme activity was increased to 5.1 times by adding NaCl to a final concentration of 0.5M. Strain ALW1 alginate lyase produced disaccharide (majority) and trisaccharide from alginate indicating that this enzyme could be a good tool for preparation of alginate oligosaccharides with low degree of polymerization (DP). The alginate oligosaccharides displayed the scavenging abilities towards radicals (DPPH, ABTS(+) and hydroxyl) and the reducing power. Therefore, the hydrolysates exhibited the antioxidant activity and had potential as a natural antioxidant. PMID- 26686614 TI - Comparative analysis of the gastrointestinal microbial communities of bar-headed goose (Anser indicus) in different breeding patterns by high-throughput sequencing. AB - The bar-headed goose is currently one of the most popular species for rare birds breeding in China. However, bar-headed geese in captivity display a reduced reproductive rate. The gut microbiome has been shown to influence host factors such as nutrient and energy metabolism, immune homeostasis and reproduction. It is therefore of great scientific and agriculture value to analyze the microbial communities associated with bar-headed geese in order to improve their reproductive rate. Here we describe the first comparative study of the gut microbial communities of bar-headed geese in three different breeding pattern groups by 16SrRNA sequences using the Illumina MiSeq platform. The results showed that Firmicutes predominated (58.33%) among wild bar-headed geese followed by Proteobacteria (30.67%), Actinobacteria (7.33%) and Bacteroidetes (3.33%). In semi-artificial breeding group, Firmicutes was also the most abundant bacteria (62.00%), followed by Bacteroidetes (28.67%), Proteobacteria (4.20%), Actinobacteria (3.27%) and Fusobacteria (1.51%). The microbial communities of artificial breeding group were dominated by Firmicutes (60.67%), Fusobacteria (29.67%) and Proteobacteria (9.33%). Wild bar-headed geese had a significant higher relative abundance of Proteobacteria and Actinobacteria, while semi artificial breeding bar-headed geese had significantly more Bacteroidetes. The semi-artificial breeding group had the highest microbial community diversity and richness, followed by wild group, and then the artificial breeding group. The marked differences of genus level group-specific microbes create a baseline for future bar-headed goose microbiology research. PMID- 26686615 TI - Metabolic potential and community structure of endophytic and rhizosphere bacteria associated with the roots of the halophyte Aster tripolium L. AB - The submitted work assumes that the abundance and diversity of endophytic and rhizosphere microorganisms co-existing with the halophytic plant Aster tripolium L. growing in a salty meadow in the vicinity of a soda factory (central Poland) represent unique populations of cultivable bacterial strains. Endophytic and rhizosphere bacteria were (i) isolated and identified based on 16S rDNA sequences; (ii) screened for nifH and acdS genes; and (iii) analyzed based on selected metabolic properties. Moreover, total microbial biomass and community structures of the roots (endophytes), rhizosphere and soil were evaluated using a cultivation-independent technique (PLFA) to characterize plant-microbial interactions under natural salt conditions. The identification of the isolated strains showed domination by Gram-positive bacteria (mostly Bacillus spp.) both in the rhizosphere (90.9%) and roots (72.7%) of A. tripolium. Rhizosphere bacterial strains exhibited broader metabolic capacities, while endophytes exhibited higher specificities for metabolic activity. The PLFA analysis showed that the total bacterial biomass decreased in the following order (rhizosphereAKT->mTORC1-signaling pathway, is an important regulator of dormant intestinal stem cells (d-ISCs). Acute nutrient deprivation leads to transient PTEN phosphorylation within d-ISCs and a corresponding increase in their number. This release of PTEN inhibition renders d-ISCs functionally poised to contribute to the regenerative response during re-feeding via cell-autonomous activation of the PI3K->AKT->mTORC1 pathway. Consistent with its role in mediating cell survival, PTEN is required for d-ISC maintenance at baseline, and intestines lacking PTEN have diminished regenerative capacity after irradiation. Our results highlight a PTEN-dependent mechanism for d-ISC maintenance and further demonstrate the role of d-ISCs in the intestinal response to stress. PMID- 26686632 TI - Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs. AB - Whether aged hematopoietic stem and progenitor cells (HSPCs) have impaired DNA damage repair is controversial. Using a combination of DNA mutation indicator assays, we observe a 2- to 3-fold increase in the number of DNA mutations in the hematopoietic system upon aging. Young and aged hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) do not show an increase in mutation upon irradiation-induced DNA damage repair, and young and aged HSPCs respond very similarly to DNA damage with respect to cell-cycle checkpoint activation and apoptosis. Both young and aged HSPCs show impaired activation of the DNA-damage induced G1-S checkpoint. Induction of chronic DNA double-strand breaks by zinc finger nucleases suggests that HSPCs undergo apoptosis rather than faulty repair. These data reveal a protective mechanism in both the young and aged hematopoietic system against accumulation of mutations in response to DNA damage. PMID- 26686633 TI - T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-gamma Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma. AB - USP15 is a deubiquitinase that negatively regulates activation of naive CD4(+) T cells and generation of IFN-gamma-producing T helper 1 (Th1) cells. USP15 deficiency in mice promotes antitumor T cell responses in a transplantable cancer model; however, it has remained unclear how deregulated T cell activation impacts primary tumor development during the prolonged interplay between tumors and the immune system. Here, we find that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA)-induced fibrosarcomas. Excessive IFN-gamma production in USP15-deficient mice promotes expression of the immunosuppressive molecule PD-L1 and the chemokine CXCL12, causing accumulation of T-bet(+) regulatory T cells and CD11b(+)Gr-1(+) myeloid-derived suppressor cells at tumor site. Mixed bone marrow adoptive transfer studies further reveals a T cell-intrinsic role for USP15 in regulating IFN-gamma production and tumor development. These findings suggest that T cell intrinsic USP15 deficiency causes excessive production of IFN-gamma, which promotes an immunosuppressive tumor microenvironment during MCA-induced primary tumorigenesis. PMID- 26686634 TI - Context-Specific Effects of TGF-beta/SMAD3 in Cancer Are Modulated by the Epigenome. AB - The transforming growth factor beta (TGF-beta) signaling pathway exerts opposing effects on cancer cells, acting as either a tumor promoter or a tumor suppressor. Here, we show that these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGF-beta signaling, and the distinct epigenomes of breast-tumor-initiating cells (BTICs). These effects of TGF-beta are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC-suppressing contexts. Our data show cell-type-specific patterns of DNA and histone modifications provide a modulatory layer by determining accessibility of genes to regulation by TGF-beta/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status and is crucial for TGF-beta-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGF-beta in cancer. PMID- 26686635 TI - Nucleotide Pool Depletion Induces G-Quadruplex-Dependent Perturbation of Gene Expression. AB - Nucleotide pool imbalance has been proposed to drive genetic instability in cancer. Here, we show that slowing replication forks by depleting nucleotide pools with hydroxyurea (HU) can also give rise to both transient and permanent epigenetic instability of a reporter locus, BU-1, in DT40 cells. HU induces stochastic formation of Bu-1(low) variants in dividing cells, which have lost the H3K4me3 present in untreated cells. This instability is potentiated by an intragenic G quadruplex, which also promotes local H2Ax phosphorylation and transient heterochromatinization. Genome-wide, gene expression changes induced by HU significantly overlap with those resulting from loss of the G4-helicases FANCJ, WRN, and BLM. Thus, the effects of global replication stress induced by nucleotide pool depletion can be focused by local replication impediments caused by G quadruplex formation to induce epigenetic instability and changes in gene expression, a mechanism that may contribute to selectable transcriptional changes in cancer. PMID- 26686636 TI - Preservation of Gene Duplication Increases the Regulatory Spectrum of Ribosomal Protein Genes and Enhances Growth under Stress. AB - In baker's yeast, the majority of ribosomal protein genes (RPGs) are duplicated, and it was recently proposed that such duplications are preserved via the functional specialization of the duplicated genes. However, the origin and nature of duplicated RPGs' (dRPGs) functional specificity remain unclear. In this study, we show that differences in dRPG functions are generated by variations in the modality of gene expression and, to a lesser extent, by protein sequence. Analysis of the sequence and expression patterns of non-intron-containing RPGs indicates that each dRPG is controlled by specific regulatory sequences modulating its expression levels in response to changing growth conditions. Homogenization of dRPG sequences reduces cell tolerance to growth under stress without changing the number of expressed genes. Together, the data reveal a model where duplicated genes provide a means for modulating the expression of ribosomal proteins in response to stress. PMID- 26686637 TI - Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca(2+) Influx but Only Modestly Influenced by Mitochondria. AB - Axon injury leads to rapid depletion of NAD-biosynthetic enzyme NMNAT2 and high levels of its substrate, NMN. We proposed a key role for NMN in Wallerian degeneration but downstream events and their relationship to other mediators remain unclear. Here, we show, in vitro and in vivo, that axotomy leads to a late increase in intra-axonal Ca(2+), abolished by pharmacological or genetic reduction of NMN levels. NMN requires the pro-degenerative protein SARM1 to stimulate Ca(2+) influx and axon degeneration. While inhibition of NMN synthesis and SARM1 deletion block Ca(2+) rise and preserve axonal integrity, they fail to prevent early mitochondrial dynamic changes. Furthermore, depolarizing mitochondria does not alter the rate of Wallerian degeneration. These data reveal that NMN and SARM1 act in a common pathway culminating in intra-axonal Ca(2+) increase and fragmentation and dissociate mitochondrial dysfunctions from this pathway, elucidating which steps may be most effective as targets for therapy. PMID- 26686638 TI - Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis. AB - We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value. PMID- 26686639 TI - Crystal Structure of a Eukaryotic GEN1 Resolving Enzyme Bound to DNA. AB - We present the crystal structure of the junction-resolving enzyme GEN1 bound to DNA at 2.5 A resolution. The structure of the GEN1 protein reveals it to have an elaborated FEN-XPG family fold that is modified for its role in four-way junction resolution. The functional unit in the crystal is a monomer of active GEN1 bound to the product of resolution cleavage, with an extensive DNA binding interface for both helical arms. Within the crystal lattice, a GEN1 dimer interface juxtaposes two products, whereby they can be reconnected into a four-way junction, the structure of which agrees with that determined in solution. The reconnection requires some opening of the DNA structure at the center, in agreement with permanganate probing and 2-aminopurine fluorescence. The structure shows that a relaxation of the DNA structure accompanies cleavage, suggesting how second-strand cleavage is accelerated to ensure productive resolution of the junction. PMID- 26686640 TI - Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase. AB - Mcm2-7 helicase is loaded onto double-stranded origin DNA as an inactive double hexamer (DH) in G1 phase. The mechanisms of Mcm2-7 remodeling that trigger helicase activation in S phase remain unknown. Here, we develop an approach to detect and purify the endogenous DHs directly. Through cellular fractionation, we provide in vivo evidence that DHs are assembled on chromatin in G1 phase and separated during S phase. Interestingly, Mcm10, a robust MCM interactor, co purifies exclusively with the DHs in the context of chromatin. Deletion of the main interaction domain, Mcm10 C terminus, causes growth and S phase defects, which can be suppressed through Mcm10-MCM fusions. By monitoring the dynamics of MCM DHs, we show a significant delay in DH dissolution during S phase in the Mcm10-MCM interaction-deficient mutants. Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell-cycle-regulated supercomplex with DHs. PMID- 26686641 TI - The Localization and Action of Topoisomerase IV in Escherichia coli Chromosome Segregation Is Coordinated by the SMC Complex, MukBEF. AB - The type II topoisomerase TopoIV, which has an essential role in Escherichia coli chromosome decatenation, interacts with MukBEF, an SMC (structural maintenance of chromosomes) complex that acts in chromosome segregation. We have characterized the intracellular dynamics of individual TopoIV molecules and the consequences of their interaction with MukBEF clusters by using photoactivated-localization microscopy. We show that ~15 TopoIV molecules per cell are associated with MukBEF clusters that are preferentially localized to the replication origin region (ori), close to the long axis of the cell. A replication-dependent increase in the fraction of immobile molecules, together with a proposed catalytic cycle of ~1.8 s, is consistent with the majority of active TopoIV molecules catalyzing decatenation, with a minority maintaining steady-state DNA supercoiling. Finally, we show that the MukB-ParC interaction is crucial for timely decatenation and segregation of newly replicated ori DNA. PMID- 26686642 TI - Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation. AB - F-BAR domain proteins regulate and sense membrane curvature by interacting with negatively charged phospholipids and assembling into higher-order scaffolds. However, regulatory mechanisms controlling these interactions are poorly understood. Here, we show that Drosophila Nervous Wreck (Nwk) is autoregulated by a C-terminal SH3 domain module that interacts directly with its F-BAR domain. Surprisingly, this autoregulation does not mediate a simple "on-off" switch for membrane remodeling. Instead, the isolated Nwk F-BAR domain efficiently assembles into higher-order structures and deforms membranes only within a limited range of negative membrane charge, and autoregulation elevates this range. Thus, autoregulation could either reduce membrane binding or promote higher-order assembly, depending on local cellular membrane composition. Our findings uncover an unexpected mechanism by which lipid composition directs membrane remodeling. PMID- 26686644 TI - Quantification of Protein Levels in Single Living Cells. AB - Accurate measurement of the amount of specific protein a cell produces is important for investigating basic molecular processes. We have developed a technique that allows for quantitation of protein levels in single cells in vivo. This protein quantitation ratioing (PQR) technique uses a genetic tag that produces a stoichiometric ratio of a fluorescent protein reporter and the protein of interest during protein translation. The fluorescence intensity is proportional to the number of molecules produced of the protein of interest and is used to determine the relative amount of protein within the cell. We use PQR to quantify protein expression of different genes using quantitative imaging, electrophysiology, and phenotype. We use genome editing to insert Protein Quantitation Reporters into endogenous genomic loci in three different genomes for quantitation of endogenous protein levels. The PQR technique will allow for a wide range of quantitative experiments examining gene-to-phenotype relationships with greater accuracy. PMID- 26686643 TI - Mevalonate Pathway Regulates Cell Size Homeostasis and Proteostasis through Autophagy. AB - Balance between cell growth and proliferation determines cell size homeostasis, but little is known about how metabolic pathways are involved in the maintenance of this balance. Here, we perform a screen with a library of clinically used drug molecules for their effects on cell size. We find that statins, inhibitors of the mevalonate pathway, reduce cell proliferation and increase cell size and cellular protein density in various cell types, including primary human cells. Mevalonate pathway effects on cell size and protein density are mediated through geranylgeranylation of the small GTPase RAB11, which is required for basal autophagic flux. Our results identify the mevalonate pathway as a metabolic regulator of autophagy and expose a paradox in the regulation of cell size and proteostasis, where inhibition of an anabolic pathway can cause an increase in cell size and cellular protein density. PMID- 26686645 TI - Spatial and temporal distribution patterns of the silver mojarra Eucinostomus argenteus (Perciformes: Gerreidae) in a tropical semi-enclosed bay. AB - This study determined the spatial and temporal distributions of the silver mojarra Eucinostomus argenteus (Perciformes: Gerreidae), one of the most abundant teleost species in bays and estuaries. Sampling was conducted from July 2005 to June 2007. The species was captured on all sampling dates and at six of the seven sampling stations. Approximately 80% of the individuals were below the size of first sexual maturity (12.0 cm total length, LT ). Although the spatial distribution of juveniles and adults differed throughout the study period, the environmental variables measured explained only a small part of their distribution. The recruitment period occurred during the first part of each year. Despite the high pollution levels in Guanabara Bay, this coastal system plays an important role as a nursery ground and for the growth of E. argenteus. PMID- 26686646 TI - Cytotoxicity assessment of porous silicon microparticles for ocular drug delivery. AB - Porous silicon (PSi) is a promising material for the delivery and sustained release of therapeutic molecules in various tissues. Due to the constant rinsing of cornea by tear solution as well as the short half-life of intravitreal drugs, the eye is an attractive target for controlled drug delivery systems, such as PSi microparticles. Inherent barriers ensure that PSi particles are retained in the eye, releasing drugs at the desired speed until they slowly break down into harmless silicic acid. Here, we have examined the in vitro cytotoxicity of positively and negatively charged thermally oxidized (TOPSi) and thermally carbonized (TCPSi) porous silicon microparticles on human corneal epithelial (HCE) and retinal pigment epithelial (ARPE-19) cells. In addition to ocular assessment under an inverted microscope, cellular viability was evaluated using the CellTiter BlueTM, CellTiter FluorTM, and lactate dehydrogenase (LDH) assays. CellTiter Fluor proved to be a suitable assay but due to non-specific and interfering responses, neither CellTiter Blue nor LDH assays should be used when evaluating PSi particles. Our results suggest that the toxicity of PSi particles is concentration-dependent, but at least at concentrations less than 200MUg/ml, both positively and negatively charged PSi particles are well tolerated by human corneal and retinal epithelial cells and therefore applicable for delivering drug molecules into ocular tissues. PMID- 26686647 TI - Ethylcellulose film coating of guaifenesin-loaded pellets: A comprehensive evaluation of the manufacturing process to prevent drug migration. AB - The aim of the research was to investigate the complete process of pellet production in a Wurster fluidized bed coater in order to determine the main factors affecting the migration phenomenon of a soluble API through the ethycellulose film coating (Surelease(r)) and hence the long-term stability of the controlled release pellets. Guaifenesin (GFN), as BCS class I model drug, was layered on sugar spheres using a binder-polymer solution containing the dissolved GFN. The drug loaded pellets were then coated with Surelease(r). The influence of drug loading (4.5-20.0% w/w), curing conditions (40-60 degrees C and dynamic static equipment), coating level (12-20% theoretical weight gain) and composition of the binder-layering solution (hypromellose versus Na alginate) on process efficiency (RSDW%), GFN content uniformity (RSDC%), GFN solid state (DSC and XRD) and pellet release profiles was evaluated. The effectiveness of the Surelease film was strongly affected by the ability of GFN to cross the coating layer and to recrystallize on the pellet surface. Results indicated that this behaviour was dependent on the polymer used in the binder-layering solution. Using hypromellose as polymer, GFN recrystallized on the coated pellet surface at both drug loadings. The curing step was necessary to stabilize the film effectiveness at the higher drug loading. Increasing the coating level delayed but did not prevent the GFN diffusion. Replacing hypromellose with Na alginate, reduced the migration of GFN through the film to a negligible amount even after six months of storage and the curing step was not necessary to achieve stable controlled release profiles over storage. PMID- 26686648 TI - How to adjust dexamethasone mobility in silicone matrices: A quantitative treatment. AB - Silicone-based drug delivery systems offer a great potential to improve the therapeutic efficacy and safety of a large variety of medical treatments, e.g. allowing for local long-term delivery of active agents to the inner ear. Different formulation parameters can be varied to adjust desired drug release kinetics. However, often only qualitative information is available on their effects, and product optimization is cumbersome. The aim of this study was to provide a quantitative analysis, allowing also for theoretical predictions of the impact of the device design on system performance. Dexamethasone was incorporated into thin films based on different types of silicones (e.g. varying in the type of side chains and contents of amorphous silica), optionally containing different types and amounts of poly(ethylene glycol) (PEG) (5% or 10%). Furthermore, the initial drug content was altered (from 10% to 50%). In most cases, an analytical solution of Fick's second law could be used to describe the resulting drug release kinetics from the films and to determine the respective "apparent" diffusion coefficient of the drug (which varied from 2*10(-14) to 2*10( 12)cm(2)/s, depending on the system's composition). Thus, the impact of the investigated formulation parameters on drug mobility in the polymeric matrices could be quantitatively described. Importantly, the knowledge of the "apparent" drug diffusivity can be used to theoretically predict the resulting release kinetics from dosage forms of arbitrary size and shape. For instance, dexamethasone release was theoretically predicted from cylindrical extrudates based on a selection of different silicone types. Interestingly, these predictions could be confirmed by independent experiments. Hence, this type of quantitative analysis can replace time-consuming and cost-intensive series of trial-and-error experiments during product optimization. This is particularly helpful, if long-term drug release (e.g., during several weeks, months or years) is targeted. PMID- 26686649 TI - Topical iontophoretic delivery of ionizable, biolabile aciclovir prodrugs: A rational approach to improve cutaneous bioavailability. AB - The objective was to investigate the topical iontophoretic delivery of a series of amino acid ester prodrugs of aciclovir (ACV-X, where ACV=aciclovir and X=Arg, Gly, Ile, Phe, Trp and Val) as a means to enhance cutaneous delivery of ACV. The newly synthesized prodrugs were characterized by (1)H NMR and high resolution mass spectrometry. Analytical methods using HPLC-UV were developed for their quantification and each method was validated. Investigation of solution stability as a function of pH showed that all ACV-X prodrugs were relatively stable in acid conditions at pH 2.0 and pH 5.5 for up to 8h but susceptible to extensive hydrolysis at pH 7.4 and under alkaline conditions (pH 10). No ACV-X hydrolysis was observed after contact for 2h with the external surface of porcine stratum corneum. However, there was significant hydrolysis following contact with the dermal surface of dermatomed porcine skin, in particular, for ACV-Arg. Passive transport of ACV and ACV-X prodrugs from aqueous solution after 2h was below the limit of detection. Iontophoresis of ACV at 0.5 mA/cm(2) for 2h led to modest ACV skin deposition (QDEP,ACV) of 4.6 +/- 0.3 nmol/cm(2). In contrast, iontophoresis of ACV-X prodrugs under the same conditions produced order of magnitude increases in cutaneous deposition of ACV species, that is, QDEP,TOTAL=QDEP,ACV+QDEP,ACV-X. QDEP,TOTAL for ACV-Gly, ACV-Val, ACV-Ile, ACV-Phe, ACV-Trp and ACV-Arg was 412.8 +/- 44.0, 358.8 +/- 66.8, 434.1 +/- 68.2, 249.8 +/- 81.4, 156.1 +/- 76.3, 785.9 +/- 78.1 nmol/cm(2), respectively. The extent of bioconversion of ACV-X to ACV in the skin was high and the proportion of ACV present ranged from 81% to 100%. The skin retention ratio, a measure of the selectivity of ACV species for deposition over permeation after iontophoretic delivery of ACV-X prodrugs, was dependent on both the rate of transport and the susceptibility to hydrolysis of the prodrugs. Skin deposition of ACV and its six prodrugs were investigated further as a function of current density (0.125, 0.25 and 0.5 mA/cm(2)); the effect of duration of current application (5, 10, 30, 60 and 120 min) was evaluated using ACV-Arg and ACV-Ile. Iontophoresis of ACV-Arg and ACV-Ile at 0.25 mA/cm(2) for only 5 min resulted in the deposition of appreciable amounts of ACV (36.4 +/- 5.7n mol/cm(2) and 40.3 +/- 6.1 nmol/cm(2), respectively), corresponding to supra therapeutic average concentrations in skin against HSV-1 or HSV-2. The results demonstrated that cutaneous bioavailability of ACV could be significantly improved after short-duration iontophoresis of ionizable, biolabile ACV-X prodrugs. PMID- 26686650 TI - Influence of temperature and relative humidity conditions on the pan coating of hydroxypropyl cellulose molded capsules. AB - In a previous study, hydroxypropyl cellulose (HPC)-based capsular shells prepared by injection molding and intended for pulsatile release were successfully coated with 10mg/cm(2) Eudragit(r) L film. The suitability of HPC capsules for the development of a colon delivery platform based on a time dependent approach was demonstrated. In the present work, data logging devices (PyroButton(r)) were used to monitor the microenvironmental conditions, i.e. temperature (T) and relative humidity (RH), during coating processes performed under different spray rates (1.2, 2.5 and 5.5g/min). As HPC-based capsules present special features, a preliminary study was conducted on commercially available gelatin capsules for comparison purposes. By means of PyroButton data-loggers it was possible to acquire information about the impact of the effective T and RH conditions experienced by HPC substrates during the process on the technological properties and release performance of the coated systems. The use of increasing spray rates seemed to promote a tendency of the HPC shells to slightly swell at the beginning of the spraying process; moreover, capsules coated under spray rates of 1.2 and 2.5g/min showed the desired release performance, i.e. ability to withstand the acidic media followed by the pulsatile release expected for uncoated capsules. Preliminary stability studies seemed to show that coating conditions might also influence the release performance of the system upon storage. PMID- 26686651 TI - CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. AB - Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF/cohesin-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes toward CTCF foci for coordinated transcription. Furthermore, we show that haplotype variants and allelic interactions have differential effects on chromosome configuration, influencing gene expression, and may provide mechanistic insights into functions associated with disease susceptibility. 3D genome simulation suggests a model of chromatin folding around chromosomal axes, where CTCF is involved in defining the interface between condensed and open compartments for structural regulation. Our 3D genome strategy thus provides unique insights in the topological mechanism of human variations and diseases. PMID- 26686652 TI - A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming. AB - Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically-induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates. PMID- 26686654 TI - Neuroinflammatory TNFalpha Impairs Memory via Astrocyte Signaling. AB - The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor-alpha (TNFalpha). To date, however, no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here, we show that local increase of TNFalpha in the hippocampal dentate gyrus activates astrocyte TNF receptor type 1 (TNFR1), which in turn triggers an astrocyte-neuron signaling cascade that results in persistent functional modification of hippocampal excitatory synapses. Astrocytic TNFR1 signaling is necessary for the hippocampal synaptic alteration and contextual learning-memory impairment observed in experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis (MS). This process may contribute to the pathogenesis of cognitive disturbances in MS, as well as in other CNS conditions accompanied by inflammatory states or infections. PMID- 26686655 TI - Engineering Heteromaterials to Control Lithium Ion Transport Pathways. AB - Safe and efficient operation of lithium ion batteries requires precisely directed flow of lithium ions and electrons to control the first directional volume changes in anode and cathode materials. Understanding and controlling the lithium ion transport in battery electrodes becomes crucial to the design of high performance and durable batteries. Recent work revealed that the chemical potential barriers encountered at the surfaces of heteromaterials play an important role in directing lithium ion transport at nanoscale. Here, we utilize in situ transmission electron microscopy to demonstrate that we can switch lithiation pathways from radial to axial to grain-by-grain lithiation through the systematic creation of heteromaterial combinations in the Si-Ge nanowire system. Our systematic studies show that engineered materials at nanoscale can overcome the intrinsic orientation-dependent lithiation, and open new pathways to aid in the development of compact, safe, and efficient batteries. PMID- 26686653 TI - Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. AB - Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. PMID- 26686656 TI - Emotional security in the family system and psychological distress in female survivors of child sexual abuse. AB - The Emotional Security Theory (EST) was originally developed to investigate the association between high levels of interparental conflict and child maladaptative outcome. The objective of the present study was to analyze the effects of emotional security in the family system on psychological distress among a sample of young female adult survivors of child sexual abuse (CSA). The role of emotional security was investigated through the interactive effects of a number of factors including the type of abuse, the continuity of abuse, the relationship with the perpetrator and the existence of disclosure for the abuse. Participants were 167 female survivors of CSA. Information about the abuse was obtained from a self-reported questionnaire. Emotional security was assessed with the Security in the Family System (SIFS) Scale, and the Symptom Checklist-90-Revised (SCL-90-R) was used to assess psychological distress. In the total sample, insecurity (preoccupation and disengagement) was correlated with high psychological distress scores, whereas no relationship was found between security and psychological distress. The relationship between emotional insecurity and psychological distress was stronger in cases of continued abuse and non-disclosure, while the relationship between emotional security and distress was stronger in cases of extrafamilial abuse and especially isolated or several incidents and when a disclosure had been made. No interactive effect was found between any of the three emotional variables and the type of abuse committed. The results of the current study suggest that characteristics of CSA such as relationship with the perpetrator and, especially, continuity of abuse and whether or not disclosure had been made, can affect the impact of emotional security on psychological distress of CSA survivors. PMID- 26686659 TI - The Ettention software package. AB - We present a novel software package for the problem "reconstruction from projections" in electron microscopy. The Ettention framework consists of a set of modular building-blocks for tomographic reconstruction algorithms. The well-known block iterative reconstruction method based on Kaczmarz algorithm is implemented using these building-blocks, including adaptations specific to electron tomography. Ettention simultaneously features (1) a modular, object-oriented software design, (2) optimized access to high-performance computing (HPC) platforms such as graphic processing units (GPU) or many-core architectures like Xeon Phi, and (3) accessibility to microscopy end-users via integration in the IMOD package and eTomo user interface. We also provide developers with a clean and well-structured application programming interface (API) that allows for extending the software easily and thus makes it an ideal platform for algorithmic research while hiding most of the technical details of high-performance computing. PMID- 26686660 TI - Measurement of the permittivity and loss of high-loss materials using a Near Field Scanning Microwave Microscope. AB - In this paper improvements to a Near-Field Scanning Microwave Microscope (NSMM) are presented that allow the loss of high loss dielectric materials to be measured accurately at microwave frequencies. This is demonstrated by measuring polar liquids (loss tangent tandelta~1) for which traceable data is available. The instrument described uses a wire probe that is electromagnetically coupled to a resonant cavity. An optical beam deflection system is incorporated within the instrument to allow contact mode between samples and the probe tip to be obtained. Liquids are contained in a measurement cell with a window of ultrathin glass. The calibration process for the microscope, which is based on image-charge electrostatic models, has been adapted to use the Laplacian 'complex frequency'. Measurements of the loss tangent of polar liquids that are consistent with reference data were obtained following calibration against single-crystal specimens that have very low loss. PMID- 26686661 TI - Effects of instrument imperfections on quantitative scanning transmission electron microscopy. AB - Several instrumental imperfections of transmission electron microscopes are characterized and their effects on the results of quantitative scanning electron microscopy (STEM) are investigated and quantified using simulations. Methods to either avoid influences of these imperfections during acquisition or to include them in reference calculations are proposed. Particularly, distortions inflicted on the diffraction pattern by an image-aberration corrector can cause severe errors of more than 20% if not accounted for. A procedure for their measurement is proposed here. Furthermore, afterglow phenomena and nonlinear behavior of the detector itself can lead to incorrect normalization of measured intensities. Single electrons accidentally impinging on the detector are another source of error but can also be exploited for threshold-less calibration of STEM images to absolute dose, incident beam current determination and measurement of the detector sensitivity. PMID- 26686657 TI - Roles for mismatch repair family proteins in promoting meiotic crossing over. AB - The mismatch repair (MMR) family complexes Msh4-Msh5 and Mlh1-Mlh3 act with Exo1 and Sgs1-Top3-Rmi1 in a meiotic double strand break repair pathway that results in the asymmetric cleavage of double Holliday junctions (dHJ) to form crossovers. This review discusses how meiotic roles for Msh4-Msh5 and Mlh1-Mlh3 do not fit paradigms established for post-replicative MMR. We also outline models used to explain how these factors promote the formation of meiotic crossovers required for the accurate segregation of chromosome homologs during the Meiosis I division. PMID- 26686662 TI - Advancing FIB assisted 3D EBSD using a static sample setup. AB - A new setup for automatic 3D EBSD data collection in static mode has been developed using a conventional FIB-SEM system. This setup requires no stage or sample movements between the FIB milling and EBSD mapping. Its capabilities were tested experimentally on a coherent twin boundary of an INCONEL sample. Our result demonstrates that this static setup holds many advantages in terms of data throughput and quality as compared with other ones requiring stage/sample movements. The most important advantages are the better slice alignment and an improved orientation precision in 3D space, both being prerequisite for a reliable grain boundary characterization. PMID- 26686663 TI - Efficient mucus permeation and tight junction opening by dissociable "mucus inert" agent coated trimethyl chitosan nanoparticles for oral insulin delivery. AB - Oral administration of protein drugs is greatly impeded by the lack of drug carriers that can efficiently overcome the absorption barriers of mucosa tissue, which consists of not only epithelium but also a blanket of mucus gel. We herein report a novel self-assembled nanoparticle (NP) platform for oral delivery of insulin by facilitating the efficient permeation through both of these two barriers. The NP possesses a core composed of insulin and trimethyl chitosan (TMC), and a dissociable "mucus-inert" hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivative. The NPs exhibited free Brownian motion and excellent permeability in mucus, which enabled the access of the NP core to the epithelial cell surface underneath the mucus. Moreover, investigation of NP behavior showed that the pHPMA molecules started to dissociate as the NP permeates through mucus, and the TMC NP core was then exposed to facilitate transepithelial transport via paracellular pathway. The pHPMA coating significantly improved transepithelial transport of TMC-based NP and their ability to open tight junctions between the mucus-secreting epithelial cells. Moreover, in diabetic rats, pHPMA coated NPs generated a prominent hypoglycemic response following oral administration, and exhibited a relative bioavailability 2.8-fold higher than that of uncoated TMC-based NPs. Our study provided the evidence of using pHPMA as "mucus-inert" agent to enhance mucus permeation of TMC based NPs, and validated a novel strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and TMC-based core possessing tight junction-opening ability. PMID- 26686664 TI - Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy. AB - To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase. The morphology and size of CS-ATC-DOX were determined by ATC content. In the group with 1.5mg/ml of ATC loaded CS-ATC-DOX (CS-ATC2-DOX), the drug content and loading efficiency were 8.5% and 99.1%, respectively. The ROS sensitive drug release of CS-ATC2-DOX was confirmed under in vitro physiological conditions. The results demonstrated that 1.67 times higher DOX release occurred in CS-ATC2-DOX for 48h compared to CS-DOX (ATC absent sample). Drug release and nanocomplex destruction were induced by ROS mediated ATC degradation. We determined that 66.7% of ROS was scavenged by CS-ATC2-DOX. Additionally, an HCT-116 tumor bearing animal model was used to confirm ROS sensitive therapeutic effects of CS-ATC2-DOX. The results indicate that DOX was released from the intravenously injected CS-ATC2-DOX in the tumor tissue. Thus, nuclei shrinkage and dead cells were observed in H&E staining and TUNEL assay, respectively. These data suggest that the tumor growth was effectively inhibited. This study means that CS-ATC2-DOX has potential in improving tumor therapy. PMID- 26686665 TI - Design and Synthesis of Substituted Pyridazinone-1-Acetylhydrazones as Novel Phosphodiesterase 4 Inhibitors. AB - A series of novel pyridazin-6-one-1-acetylhydrazone hybrids were rationally designed to inhibit phosphodiesterase 4 (PDE4B). The prepared compounds were evaluated for their in vitro ability to inhibit the PDE4B enzyme; several of these compounds showed moderate activity compared to the reference drug, rolipram. Compounds 6, 12, and 14 emerged as the most potent inhibitors in this series. The [3-(4-methoxyphenyl)-6-oxo-5,6-dihydro-4H-pyridazin-1-yl]acetic acid [1-(3,4,5-trimethoxyphenyl)ethylidene]hydrazide (12) showed an IC50 value of 13 MUM against PDE4B. Docking of 6, 12, and 14 into the active site of PDE4B illustrates their possible binding mode and provides insights for further optimization of this drug scaffold. PMID- 26686666 TI - Fixational eye movements and perception. PMID- 26686667 TI - Bidirectional associations between alcohol consumption and health-related quality of life amongst young and middle-aged women. AB - BACKGROUND: Evidence from cross-sectional studies has suggested a positive association between moderate alcohol consumption and health-related quality of life but prospective data remain scarce. OBJECTIVES: To examine the bidirectional relationships between alcohol consumption and health-related quality of life using a longitudinal study design. METHODS: A total of 92 448 participants of the Nurses' Health Study II reported their alcohol consumption (in 1991, 1995, 1999 and 2003) and health-related quality of life (in 1993, 1997 and 2001). Using generalized estimating equations, we modelled the physical and mental component summary (PCS and MCS) scores as a function of alcohol consumption 2 years earlier (n = 88 363) and vice versa (n = 84 621). RESULTS: Greater alcohol consumption was associated with better PCS scores 2 years later in a dose-response manner up to ~1 serving daily [mean difference (beta) = 0.67 +/- 0.06 PCS units, for moderate versus infrequent drinkers]. After adjustment for previous PCS, a similar but attenuated pattern was observed (beta = 0.33 +/- 0.07). Moderate alcohol consumption was not related to MCS, whereas moderate-to-heavy alcohol consumption was associated with lower MCS scores (beta = -0.34 +/- 0.15). Higher PCS scores were associated with greater alcohol consumption 2 years later, also after adjustment for previous alcohol consumption (beta = 0.53 +/- 0.05 g day(-1) ). MCS was not associated with alcohol consumption 2 years later. CONCLUSION: Amongst young and middle-aged women, moderate alcohol intake was associated with a small improvement in physical health-related quality of life 2 years later and vice versa. Moderate alcohol consumption was not associated with mental health related quality of life in either direction. PMID- 26686668 TI - Reorganization of functionally connected brain subnetworks in high-functioning autism. AB - Previous functional connectivity studies have found both hypo- and hyper connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism. PMID- 26686670 TI - Braak staging, plaque pathology, and APOE status in elderly persons without cognitive impairment. AB - Clinico-pathological studies reveal that some elderly people with no cognitive impairment have high burdens of neurofibrillary tangles (NFTs), a pathology associated with Alzheimer's disease. We examined a total of 123 elderly participants without dementia and free of other neurological disorders or pathologies who at autopsy were classified as Braak NFT stages of I-V. We found that women were significantly more likely to have a high Braak score. Significant associations were found between high Braak scores and entorhinal cortex amyloid load, combined hippocampal and entorhinal cortex amyloid loads with perceptual speed in the low Braak group after adjusting for age, gender and apolipoprotein E epsilon4 status. Elderly with preserved cognitive function show a wide range of Braak scores and plaque pathology similar to that seen in prodromal and frank Alzheimer's disease at death. These data suggest that some older people with extensive NFT and plaque pathology demonstrate brain resilience or reserve leading to preserved cognitive function. PMID- 26686669 TI - The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice. AB - The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Abeta also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Abeta load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. PMID- 26686672 TI - Part 2: outcome of acetabular fractures and associated prognostic factors-a ten year retrospective study of one hundred and fifty six operated cases with open reduction and internal fixation. AB - QUESTIONS/PURPOSES: The aim of this study was to identify prognostic factors associated with a poor quality of reduction and their relationships. METHODS: Data from medical charts for all patients admitted with acetabular fractures operated by open reduction and internal fixation (ORIF) from 2005 to 2014 were extracted. A total of 156 patients with a mean age of 40.3 years were included. All patients were reviewed at six months of follow-up. The prognostic factors analyzed were clinical and radiological factors. A new radiological parameter was also studied: the scanographic roof-arc angle. Specific statistical analysis was performed using a logistic regression model. RESULTS: Using a multivariate analysis logistic regression model: roof impaction (p = 0.001; OR = 6.59; CI 95% [2.01-20.97]), transverse + posterior wall (p = 0.03, OR = 2.52; CI 95% [1.46 13.65]) and surgeons in training (p = 0.02; OR = 1.24; CI 95% [1.07-3.32]) were three independent prognostic factors. Lower values of medial and posterior scanographic roof-arc angle were associated with unsatisfactory reduction. A significant association between unsatisfactory reduction and posterior roof arc angle < 61 degrees was found. CONCLUSIONS: Three independent prognostic factors associated with a risk of unsatisfactory reduction in ORIF for acetabular fractures were identified: roof impaction, transverse + posterior wall fracture and surgeons in training. Scanographic roof-arc angle seems to be a new prognostic factor. Level of Evidence Level 4 retrospective study. PMID- 26686671 TI - Ovarian steroids regulate gene expression in the dorsal raphe of old female macaques. AB - With extended life spans in modern humans, menopause has become a significant risk factor for depression, anxiety, loss of cognitive functions, weight gain, metabolic disease, osteoporosis, cardiovascular disease, and neurodegenerative diseases. Clinical studies have found beneficial neural effects of ovarian steroid hormone therapy (HT) during the menopausal transition and data are emerging that it can be continued long term. To further understand molecular underpinnings of the clinical studies, we used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to examine gene expression in the serotonergic dorsal raphe of old (>18 years) rhesus macaques, focusing on genes related to depression, cellular resilience, and neurodegenerative diseases. The animals were ovariectomized (Ovx, surgically menopausal) and subjected to either estradiol or estradiol plus progesterone HT, or to placebo, starting 2 months after Ovx and continuing for ~ 4 years. Significant changes were observed in 36 of 48 genes examined that encode proteins supporting serotonin neurotransmission, synapse assembly, glutamate neurotransmission, DNA repair, chaperones, ubiquinases and transport motors, as well as genes encoding proteins that have potential to delay the onset of neuropathologies. The data reveal important gene targets for chronic HT that contribute to neural health. Alternatively, the loss of ovarian steroids may lead to loss of functions at the gene level that contribute to many of the observable neural deficits after menopause. PMID- 26686673 TI - Is obesity related with periprosthetic fractures around the knee? AB - PURPOSE: Periprosthetic fracture (PPF) is a devastating complication following primary total knee arthroplasty. Obesity is currently considered a risk factor for many complications in orthopaedics, but there is no evidence in literature about the relationship between obesity and PPF around the knee. The objective of this study was to determine whether obesity is associated with a higher incidence of PPF. METHODS: All patients diagnosed of a PPF around the knee from January 2010 to December 2013 were enrolled. Forty-nine PPF (47 women and 2 men) were included, and a total of 97 patients (80 women and 17 men) were randomly obtained as a control group. Body mass index (BMI) was obtained in both groups and classified as <25 (normal), overweight (25-29.9), obese (30-34.9), very obese (35 39.9), or morbid obesity (>=40). Both groups, were also divided into subpopulations depending on the age as follows: <70, 70-75, 75-80 and >=80. Statistical analysis was performed to determine any difference in BMI >=30 kg/m2 distribution between groups. RESULTS: In the PPF group 61.22 % of the patients had a BMI over 30 kg/m2 and likewise 62.88 % of the patients in the control group. No association was found between obesity and a higher risk of PPF (p < 0.05). CONCLUSION: As a conclusion, obesity (BMI >=30 kg/m2) does not have any clinical relationship with the appearance of a periprosthetic fracture around the knee (p < 0.05). PMID- 26686674 TI - Surgical debridement with retention of spinal instrumentation and long-term antimicrobial therapy for multidrug-resistant surgical site infections after spinal surgery: a case series. AB - PURPOSE: Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI. METHODS: We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54-82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution. RESULTS: The median duration of follow-up was 868 (178-1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1-6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12 352) days and 336 (89-1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7-73) days, and the mean time for normalization of C-reactive protein was 54.5 (7-105) days. CONCLUSIONS: Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy. PMID- 26686675 TI - Content of Selected Minerals and Active Ingredients in Teas Containing Yerba Mate and Rooibos. AB - The study aimed to determine the content of selected elements: sodium, potassium, copper, zinc, iron, manganese and active ingredients such as phenolic acids and tannins in teas containing Yerba Mate and Rooibos cultivated in various areas. The study material comprised six samples of Yerba Mate teas and of Rooibos teas, both tea bags and leaves, purchased in Pulawy and online via Allegro. In total, 24 samples were tested. Yerba Mate was particularly abundant in Mn and Fe. The richest source of these elements was Yerba Mate Yer-Vita (2261.3 mg . kg(-1) d.m.) and (691.6 mg . kg(-1) d.m.). The highest content of zinc was determined in Yerba Mate Amanda with lime (106.0 mg . kg(-1) d.m.), while copper was most abundant in Yerba Mate Big-Active cocoa and vanilla (14.05 mg . kg(-1) d.m.). In Rooibos, the content of sodium was several times higher than in Yerba Mate. A clear difference was observed in the content of minerals in dry weight of the examined products, which could be a result of both the taxonomic distinctness and the origin of the raw material. Leaf teas turned out to be a better source of tannins; on the other hand, tea bags contained substantially more phenolic acids. The richest source of phenolic acids was Yer-Vita in bags (1.8 %), and the highest amount of tannins was recorded in the leaf tea Green Goucho caramel and dark chocolate (9.04 g . 100 g(-1) d.m.). In Rooibos products, the highest content of phenolic acids was recorded in tea bags (Savannah with honey and vanilla 0.96 %), and tannins in (Lord Nelson with strawberry and cream 7.99 g . 100 g (-1) d.m.). PMID- 26686676 TI - Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism. AB - Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages. PMID- 26686677 TI - Optical coherence tomography and electrophysiology of retinal and visual pathways in Wilson's disease. AB - We evaluated correlations between positive findings of changes on brain magnetic resonance imaging (MRI) and selected morphological and electrophysiological parameters of the retinal and visual systems in Wilson's disease. Fifty-eight Wilson's disease symptomatic patients were divided according to whether they displayed brain changes on MRI (positive, n = 39; negative, n = 19). All participants and healthy control group (n = 30), underwent retinal optical coherence tomography to assess the thickness of macula and the total retinal nerve fiber layer. Visual evoked potentials were measured and electroretinography was performed. Macular and retinal nerve fibers were thinner in participants with changes on MRI than in participants without changes. Electrophysiological parameters were markedly different in the MRI positive group compared with the negative group and 30 healthy controls; however, some abnormalities were evident in cases without visible brain pathology. Morphological and electrophysiological changes of retinal and visual pathways are associated with MRI visualized brain injury in Wilson's disease and may be useful for detecting the degree of neurodegeneration. PMID- 26686678 TI - Seventeen-year trends in spring and autumn phenophases of Betula pubescens in a boreal environment. AB - Trends in the timing of spring and autumn phenophases of Betula pubescens were investigated in the southern, middle, and northern boreal zones in Finland. The field observations were carried out at 21 sites in the Finnish National Phenological Network in 1997-2013. The effective temperature sum of the thermal growth period, i.e. the sum of the positive differences between diurnal mean temperatures and 5 degrees C (ETS1), increased annually on average by 6-7 degree day units. Timing of bud burst remained constant in the southern and middle boreal zones but advanced annually by 0.5 day in the northern boreal zone. The effective temperature sum at bud burst (ETS2) showed no trend in the southern and middle boreal zones, whereas ETS2 increased on average from 20-30 to 50 degree day units in the northern boreal zone, almost to the same level as in the other zones. Increase in ETS2 indicates that the trees did not start their growth in very early spring despite warmer spring temperatures. The timing of leaf colouring and leaf fall remained almost constant in the southern boreal zones, whereas these advanced annually by 0.3 and 0.6 day in the middle boreal zone and by 0.6 and 0.4 day in the northern boreal zone, respectively. The duration of the growth period remained constant in all boreal zones. The results indicate high buffering capacity of B. pubescens against temperature changes. The study also shows the importance of the duration of phenological studies: some trends in spring phenophases had levelled out, while new trends in autumn phases had emerged after earlier studies in the same network for a shorter observation period. PMID- 26686679 TI - Sleep disturbance in Mowat-Wilson syndrome. AB - Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome caused by a heterozygous mutation or deletion of the ZEB2 gene. It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. The current study investigated sleep disturbance in people with MWS. In a series of unstructured interviews focused on development and behaviors in MWS, family members frequently reported sleep disturbance, particularly early-morning waking and frequent night waking. The Sleep Disturbance Scale for Children (SDSC) was therefore administered to a sample of 35 individuals with MWS, along with the Developmental Behaviour Checklist (DBC) to measure behavioral and emotional disturbance. A high level of sleep disturbance was found in the MWS sample, with 53% scoring in the borderline range and 44% in the clinical disorder range for at least one subscale of the SDSC. Scores were highest for the Sleep-wake transition disorders subscale, with 91% of participants reaching at least the borderline disorder range. A significant positive association was found between total scores on the SDSC and the DBC Total Behaviour Problem Score. These results suggest that sleep disorders should be screened for in people with MWS, and where appropriate, referrals to sleep specialists made for management of sleep problems. PMID- 26686680 TI - Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium. AB - The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology. PMID- 26686681 TI - Application of objective physical activity measurement in an antenatal physical activity consultation intervention: a randomised controlled trial. AB - BACKGROUND: Physical Activity (PA) during pregnancy has many health benefits, however, inactivity in this population is common and PA often declines with increasing gestation. PA consultations have been useful in promoting PA in the general population, however their use for addressing PA in pregnancy is unknown. This study aimed to examine if a theory-based intervention using PA consultations would reduce the magnitude of decline in objectively measured PA between the first and third trimesters of pregnancy. METHODS: A RCT was carried out in an urban maternity unit in Northern Ireland between September 2012 and June 2013. 109 low-risk, primigravida pregnant women were randomised to a control (n = 54) or intervention group (n = 55). Intervention participants received three face-to face individual PA consultations. Daily PA was measured in each trimester using seven day accelerometry. The study was approved by a NHS trust (12/NI/0036). PA data in counts per minute (CPM) were categorised into intensity using Freedson cut points and mean minutes of PA were compared between groups using repeated measures ANOVA with a sub-analysis stratifying participants per PA level in trimester one. RESULTS: Intention to treat analysis was performed on data from 97 participants. Time in moderate, vigorous and moderate-vigorous intensity PA (MVPA) significantly declined between trimesters one and three in both groups (P < 0.001). There were no statistically significant differences in PA between groups in any trimester. Women in the intervention group who were less active in trimester one did not demonstrate a significant decline in MVPA throughout pregnancy (in contrast with the decline identified in the more active participants). CONCLUSIONS: The findings indicate that PA consultations were not effective in reducing the decline of MVPA in throughout pregnancy, however, women who were less active in trimester one and received PA consultations had a lesser decrease in MVPA. It is possible that pregnant women, specifically those who are more active at the start of pregnancy, have differing needs for PA behaviour change and maintenance, requiring more intense interventions than less active women. TRIAL REGISTRATION: Current Controlled Trials Register ISRCTN61829137. PMID- 26686683 TI - Isolated unilateral ptosis due to neurovascular conflict. PMID- 26686682 TI - The renin-angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril in clinical trials versus routine practice: insights from the prospective EARLY registry. AB - BACKGROUND: Patient characteristics and blood pressure-related outcomes in randomized clinical trials (RCTs) differ from clinical practice because of stringent selection criteria. The present study aimed to explore the relationship between clinical trials and clinical practice. We analyzed data from patients enrolled in the "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti Hypertensive Therapy" (EARLY) registry comparing blood pressure (BP) effects of the angiotensin receptor blocker (ARB) azilsartan medoxomil (AZL-M) with the angiotensin-converting enzyme (ACE) inhibitor ramipril between patients who met the eligibility criteria of a previous RCT and those who did not. METHODS: Patients with primary arterial hypertension were consecutively enrolled from primary care offices in Germany into the EARLY registry in a 7:3 ratio for treatment with AZL-M or an ACE inhibitor, provided that they met the following criteria at baseline: 1) no antihypertensive treatment prior to inclusion or a non-renin-angiotensin system (RAS) based monotherapy; 2) initiation of treatment with either AZL-M or an ACE inhibitor alone. Analyses were performed to evaluate BP effects for patients in the EARLY registry who met the selection criteria of a prior RCT (RCT+) versus those who did not (RCT-). RESULTS: Out of 3,698 patients considered, 1,644 complied with the RCT criteria (RCT+) while 2,054 did not (RCT ). RCT- patients (55.5%) displayed a higher risk profile in terms of age and comorbidities, and a wider spectrum of BP values at baseline, as highlighted by the grades of hypertension and mean BP values. The proportion of patients who achieved target blood pressure control in the RCT+ group was significantly higher for AZL-M versus ramipril (64.1 versus 56.1%; P<0.01), in accordance with the result of the clinical trial. In the RCT- AZL-M group, the proportion of patients who met BP targets was lower (58.1%) than in the RCT+ AZL-M group (64.1%), whereas the proportion of patients with target BP values in the RCT- ramipril and the RCT+ ramipril groups was similar (57.7 versus 56.1%). Thus, in contrast to results for the RCT+ group, in the RCT- group, the target BP attainment rate for AZL-M was not significantly superior to that for ramipril. However, the tolerability profile of AZL-M and ramipril was comparable in both populations. At the 12-month follow-up, death and stroke rates were low (<=0.5%) and adverse events did not differ between the AZL-M and ramipril groups, irrespective of RCT eligibility. CONCLUSIONS: These data confirm that the EARLY population comprised a broader spectrum of hypertensive patients than RCTs, and the differences in patient characteristics were accompanied by disparate rates of blood pressure goal attainment. Overall, the validity of the RCT was demonstrated and confirmed in clinical practice with a broader range of patients with various comorbidities. PMID- 26686684 TI - C22-bronchial and T7-alveolar epithelial cell lines of the immortomouse are excellent murine cell culture model systems to study pulmonary peroxisome biology and metabolism. AB - In pulmonary research, temperature-sensitive immortalized cell lines derived from the lung of the "immortomouse" (H-2k(b)-tsA58 transgenic mouse), such as C22 club cells and T7 alveolar epithelial cells type II (AECII), are frequently used cell culture models to study CC10 metabolism and surfactant synthesis. Even though peroxisomes are highly abundant in club cells and AECII and might fulfill important metabolic functions therein, these organelles have never been investigated in C22 and T7 cells. Therefore, we have characterized the peroxisomal compartment and its associated gene transcription in these cell lines. Our results show that peroxisomes are highly abundant in C22 and T7 cells, harboring a common set of enzymes, however, exhibiting specific differences in protein composition and gene expression patterns, similar to the ones observed in club cells and AECII in situ in the lung. C22 cells contain a lower number of larger peroxisomes, whereas T7 cells possess more numerous tubular peroxisomes, reflected also by higher levels of PEX11 proteins. Moreover, C22 cells harbor relatively higher amounts of catalase and antioxidative enzymes in distinct subcellular compartments, whereas T7 cells exhibit higher levels of ABCD3 and plasmalogen synthesizing enzymes as well as nuclear receptors of the PPAR family. This study suggest that the C22 and T7 cell lines of the immortomouse lung are useful models to study the regulation and metabolic function of the peroxisomal compartment and its alterations by paracrine factors in club cells and AECII. PMID- 26686685 TI - Quality of life impact of childhood skin conditions measured using the Children's Dermatology Life Quality Index (CDLQI): a meta-analysis. AB - BACKGROUND: The Children's Dermatology Life Quality Index (CDLQI) is the most widely used instrument for measuring the impact of skin disease on quality of life (QoL) in children. OBJECTIVES: To provide a meta-analysis of all published QoL scores for a range of childhood skin conditions. METHODS: Studies using the CDLQI questionnaire to measure QoL in skin conditions were identified by searching Medline and Embase from January 1995 (CDLQI creation) to December 2014. Studies were grouped according to condition and baseline scores were combined using meta-analysis. RESULTS: Sixty-seven studies using the CDLQI met the inclusion criteria. The overall estimated CDLQI scores for conditions reported more than once were [point estimate (95% confidence interval, CI), number of studies (n), score range]: atopic eczema [8.5 (7.1-9.8), n = 38, 0-29], acne [5.3 (1.9-8.5), n = 5, 0-30], alopecia [3.1 (0-7.7), n = 2, 0-6], molluscum contagiosum [3.5 (0.6-6.7), n = 5, 0-27], psoriasis [8.0 (3.9-12.1), n = 6, 0 29], scabies [9.2 (0.0-20.3), n = 2, 1-26], urticaria [7.1 (0-15.4), n = 2, 0 22], vitiligo [6.5 (0.7-12.2), n = 2, 0-20] and warts [2.9 (0-5.8), n = 4, 0-16]. Overall, the mean effect on QoL [weighted average CDLQI score 4.6 (95% CI 3.9 5.4)] for children with these conditions was small. However, many children were found to experience a very large impact on QoL (34% of children with atopic eczema, 10% with molluscum contagiosum and 1-5% with acne) in studies where the distributions of scores were provided. CONCLUSIONS: Most skin conditions in children have a 'small' mean effect on QoL. However, the range is large and a significant proportion of children with many common skin conditions will experience a very large effect on quality of life. PMID- 26686686 TI - Response to comment of Taher Rajaee and Salar Khani on "Artificial neural network modelling of biological oxygen demand in rivers at the national level with input selection based on Monte Carlo simulations" [Siljic et al., Environ Sci Pollut Res (2015) 22: 4230-4241]. PMID- 26686688 TI - Influence of Environmental Factors on Bacteriocin Production by Human Isolates of Lactococcus lactis MM19 and Pediococcus acidilactici MM33. AB - The influence of temperature, initial pH, and carbon and nitrogen sources on bacteriocin secreted by Lactococcus lactis MM19 (MM19) and Pediococcus acidilactici MM33 (MM33) was evaluated. It was found that 30 and 45 degrees C were the growth temperatures for higher nisin and pediocin production by MM19 and MM33, respectively. The initial pH values for higher production of nisin and pediocin were 9 and 6, respectively. Glucose and wheat peptone E430 were found as suitable carbon and nitrogen sources, respectively, for highest nisin production by MM19 at 30 degrees C and initial pH of 9. In these conditions, nisin production could be increased by 6.7 times as compared to the control medium (de Man, Rogosa, and Sharpe--MRS broth). Similarly, fructose and pea peptone were suitable carbon and nitrogen sources, respectively, for highest production of pediocin by MM33 at 45 degrees C and initial pH of 6. In these conditions, pediocin production by MM33 was increased by three times as compared to the control medium (tryptone-glucose-yeast extract-TGE broth). PMID- 26686689 TI - Accuracy of non-invasive continuous total hemoglobin measurement by Pulse CO Oximetry in severe traumatized and surgical bleeding patients. AB - The Masimo Radical-7 Pulse CO-Oximeter (Masimo Corp., USA) non-invasively computes hemoglobin concentration (SpHb). SpHb was compared to Co-Oximeter readings (CoOxHb) of arterial samples in surgery patients of the emergency department. Forty-six patients were enrolled. The Masimo R1 25L (revision F and G) adult adhesive sensor was attached to the ring finger of the arterially cannulated hand. Before start, every 30 min during surgery and in the case of severe bleeding SpHb and CoOxHb values were documented. SpHb and post hoc adjusted SpHb (AdSpHb) values were analyzed. Linear regression analysis and Bland Altman plot for agreement were performed. The detection failure rate of SpHb was 24.5 %. CoOxHb and SpHb showed a strong correlation (r = +0.81), but agreement was moderate [bias (LOA) of -0.6 (-3.0; +1.9)] g/dl. Positive and negative predicted value was 0.49 and 0.69. Exclusion of changes of CoOxHb values <=1 g/dl resulted in a positive and negative predictive value of 0.66 and 1.00. Post hoc adjustment of the SpHb (AdSpHb) improved linear correlation of CoOxHb and AdSpHb [r = +0.90 (p < 0.001)] but less the agreement [bias (LOA) of CoOxHb and AdSpHb = -0.1 (-2.1/+1.9) g/dl]. SpHb agreed only moderately with CoOxHb values and predicted decreases of CoOxHb only if changes of SpHb <= 1.0 g/dl were excluded. The detection failure rate of SpHb was high. At present, additional refinements of the current technology are necessary to further improve performance of non invasive hemoglobin measurement in the clinical setting. PMID- 26686687 TI - Survival regulation of leukemia stem cells. AB - Leukemia stem cells (LSCs) are a subpopulation cells at the apex of hierarchies in leukemia cells and responsible for disease continuous propagation. In this article, we discuss some cellular and molecular components, which are critical for LSC survival. These components include intrinsic signaling pathways and extrinsic microenvironments. The intrinsic signaling pathways to be discussed include Wnt/beta-catenin signaling, Hox genes, Hh pathway, Alox5, and some miRNAs, which have been shown to play important roles in regulating LSC survival and proliferation. The extrinsic components to be discussed include selectins, CXCL12/CXCR4, and CD44, which involve in LSC homing, survival, and proliferation by affecting bone marrow microenvironment. Potential strategies for eradicating LSCs will also discuss. PMID- 26686690 TI - Dynamic prediction of the need for renal replacement therapy in intensive care unit patients using a simple and robust model. AB - We aimed at identifying a model that dynamically predicts future need for renal replacement therapy (RRT) in intensive care unit (ICU) patients and can easily be implemented for online monitoring at the bedside. 7290 interdisciplinary ICU admissions were investigated. Patients with <3 days of stay or RRT in the first 2 days were excluded. 1624 of the remaining 2625 patients had a normal serum creatinine at admission. Every second of these 1624 patients was used for model calibration whereas the other half and, in addition, the 1001 patients with elevated serum creatinine were exclusively used for validation. Discriminant analysis was used to determine and validate a combination of clinical parameters that predicts the need for RRT 72 h ahead. Based on the calibration sample, stepwise discriminant analysis selected the serum values of (1) current urea, (2) current lactate, (3) the ratio of current and admission serum creatinine, and (4) the mean urine output of the previous 24 h. In the validation datasets, the model reached areas under the receiver operating characteristic curve of 0.866 and 0.833 in patients with normal and elevated serum creatinine at admission, respectively. Moreover, the model's predictive value extended to at least 5 days prior to initiation of RRT and exceeded that of the RIFLE classification at all investigated prediction intervals. We identified a robust model that dynamically predicts the future need for RRT successfully. This tool may help improve timing of therapy and prognosis in ICU patients. PMID- 26686691 TI - Heart period and blood pressure characteristics in splanchnic arterial occlusion shock-induced collapse. AB - The nature of hemodynamic instability typical of circulatory shock is not well understood, but an improved interpretation of its dynamic features could help in the management of critically ill patients. The objective of this work was to introduce new metrics for the analysis of arterial blood pressure (ABP) in order to characterize the risk of catastrophic outcome in splanchnic arterial occlusion (SAO) shock. Continuous ABP (fs = 1 kHz) was measured in rats during experimental SAO shock, which induced a fatal pressure drop (FPD) in ABP. The FPD could either be slow (SFPD) or fast (FFPD), with the latter causing cardiovascular collapse. Time series of mean arterial pressure, systolic blood pressure and heart period were derived from ABP. The sample asymmetry-based algorithm Heart Rate Characteristics was adapted to compute the Heart Period Characteristics (HPC) and the Blood Pressure Characteristics (BPC). Baroreflex sensitivity (BRS) was assessed by means of a bivariate model. The approach to FPD of the animals who collapsed (FFPD) was characterized by higher BRS in the low frequency band versus SFPD animals (0.36 +/- 0.15 vs. 0.19 +/- 0.12 ms/mmHg, p value = 0.0196), bradycardia as indicated by the HPC (0.76 +/- 0.57 vs. 1.94 +/- 1.27, p value = 0.0179) and higher but unstable blood pressure as indicated by BPC (3.02 +/- 2.87 vs. 1.47 +/- 1.29, p value = 0.0773). The HPC and BPC indices demonstrated promise as potential clinical markers of hemodynamic instability and impending cardiovascular collapse, and this animal study suggests their test in data from intensive care patients. PMID- 26686692 TI - Expression of Caveolin-1 in Periodontal Tissue and Its Role in Osteoblastic and Cementoblastic Differentiation In Vitro. AB - It has been previously reported that caveolin-1 (Cav-1) knockout mice exhibit increased bone size and stiffness. However, the expression and role of Cav-1 on periodontal tissue is poorly understood. The aim of this study was to investigate the immunohistochemical expression of Cav-1 in the mouse periodontium and explore the role of Cav-1 on osteoblastic and cementoblastic differentiation in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. To reveal the molecular mechanisms of Cav-1 activity, associated signaling pathways were also examined. Immunolocalization of Cav-1 was studied in mice periodontal tissue. Differentiation was evaluated by ALP activity, alizarin red S staining, and RT-PCR for marker genes. Signal transduction was analyzed using Western blotting and confocal microscopy. Cav-1 expression was observed in hPDLCs, cementoblasts, and osteoblasts of the periodontium both in vivo and in vitro. Inhibition of Cav-1 expression by methyl-beta-cyclodextrin (MbetaCD) and knockdown of Cav-1 by siRNA promoted osteoblastic and cementoblastic differentiation by increasing ALP activity, calcium nodule formation, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. Osteogenic medium-induced BMP-2 and BMP-7 expression, and phosphorylation of Smad1/5/8 were enhanced by MbetaCD and siRNA knockdown of Cav-1, which was reversed by BMP inhibitor noggin. MbetaCD and Cav-1 siRNA knockdown increased OM induced AMPK, Akt, GSK3beta, and CREB phosphorylation, which were reversed by Ara A, a specific AMPK inhibitor. Moreover, OM-induced activation of p38, ERK, JNK, and NF-kappaB was enhanced by Cav-1 inhibition. This study demonstrates, for the first time, that Cav-1 is expressed in developing periodontal tissue and in vitro in periodontal-related cells. Cav-1 inhibition positively regulates osteoblastic differentiation in hPDLCs, cementoblasts, and osteoblasts via BMP, AMPK, MAPK, and NF-kappaB pathway. Thus, Cav-1 inhibition may be a novel molecular target for therapeutic approaches in periodontitis or osteolytic disease. PMID- 26686693 TI - A Systematic Review of the Role of Vitamin D on Neuromuscular Remodelling Following Exercise and Injury. AB - Vitamin D is important for skeletal muscle health and deficiency is associated with clinical neuromuscular symptoms of poor strength and gait. Supplementation can independently increase muscle strength in chronically deficient populations. However, the regulatory role of vitamin D on neuromuscular remodelling and adaptation subsequent to exercise conditioning or injury has not been systematically reviewed. OBJECTIVE: to systematically review the available evidence of the role of vitamin D on neuromuscular remodelling following exercise conditioning, exercise- or experimentally induced injury. We searched Medline (OVID platform), PubMed, Embase and Web of Science for randomised controlled trials (RCTs) including measures of neuromuscular function, injury and/or inflammation; a physiologically stressful intervention involving exercise conditioning, exercise- or experimentally induced injury and; vitamin D supplementation. Nine RCTs met the inclusion criteria. Significant heterogeneity of methodological approaches and outcomes meant that meta-analysis of data was limited. Qualitative findings indicated that vitamin D may be an effective accelerant of neuromuscular remodelling in animal models (24-140 % improved recovery vs. control); the effects in humans are inconclusive and likely influenced by baseline vitamin D and supplementation strategy. Results of the meta-analyses indicated no effect of vitamin D supplementation on muscle strength adaptation following resistance training [standardised mean difference (SMD): 0.74, P = 0.42] or muscle damage (SMD: -0.03, P = 0.92), although inflammatory markers were elevated in the latter (SMD: 0.56, P = 0.04). Data from animal models offer promising and plausible mechanisms for vitamin D as an agent for neuromuscular adaptation. Further high-quality research is needed to offer clearer insight into the influential role of vitamin D in human populations. PMID- 26686694 TI - A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary. AB - This study assessed persistence and compliance with anti-osteoporosis therapies, and associations between compliance and clinical outcomes (fracture, fracture related hospitalization and death), in Hungarian women with postmenopausal osteoporosis. The study used the Hungarian National Health Insurance Fund Administration database and included women with PMO aged at least 50 years, for whom a prescription for anti-osteoporosis medication had been filled between 1 January 2004 and 31 December 2013 (index event). Persistence (prescription refilled within 8 weeks of the end of the previous supply) was evaluated over 2 years; good compliance (medication possession ratio >= 80 %) was evaluated at 1 year. Associations between compliance and clinical outcomes (data collected for up to 6 years) were assessed with adjustment for baseline covariates. A total of 296,300 women met the inclusion criteria (524,798 index events). Persistence and compliance were higher for less frequent and parenteral therapies (1- and 2-year persistence: half-yearly [parenteral] vs. daily/weekly/monthly [oral and parenteral], 81 and 38 % vs. 21-34 and 10-18 %, respectively; parenteral vs. oral, 75 and 36 % vs. 32 and 16 %; good compliance: half-yearly vs. daily/weekly/monthly, 70 vs. 24-39 %; parenteral vs. oral 78 vs. 36 %). Good compliance significantly reduced the risks of fracture, fracture-related hospitalization and death (relative risk vs. non-compliance [95 % confidence interval]: 0.77 [0.70-0.84], 0.72 [0.62-0.85] and 0.57 [0.51-0.64], respectively; P < 0.01). Improving compliance through long-interval parenteral therapies may result in clinical benefits for patients. PMID- 26686695 TI - Bone Microarchitecture in Men and Women with Diabetes: The Importance of Cortical Porosity. AB - High-resolution peripheral quantitative computed tomography (HR-pQCT) captures novel aspects of bone geometry, volumetric bone mineral density and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique to diabetic status are inconsistent in women and lacking in men. Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between bone microarchitecture from HR-pQCT of distal radius and distal tibia in 332 participants (177 men and 155 women) aged 72.1-81.4 years with or without diabetes mellitus (DM); n = 29 (18 men and 11 women) and n = 303, respectively. Statistical analyses were performed separately for women and men. The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. Participants with DM differed significantly in terms of weight in both women (70.4 +/- 12.3 vs. 80.3 +/- 18.3 kg; p = 0.015) and men (81.7 +/- 11.4 vs. 92.8 +/- 16.3 kg; p < 0.001) but no differences were found in height, smoking status, alcohol intake, social class and physical activity among women or men. Analyses in women revealed that cortical pore volume (Ct.Po.V) was higher in participants with DM and close to statistical significance for cortical porosity (Ct.Po) (beta = 0.76 [0.12, 1.41] z-score, p = 0.020 and beta = 0.62 [-0.02, 1.27] z-score, p = 0.059, respectively) at the distal radius. Adjustment for weight did not materially affect the relationship described for Ct.Po.V (beta = 0.74 [0.09, 1.39], p = 0.027) and Ct.Po (beta = 0.65 [-0.01, 1.30], p = 0.053) at the distal radius. After adjustment for weight, analyses in men revealed that Ct.Po and Ct.Po.V were higher in participants with DM (beta = 0.57 [0.09, 1.06] z-score, p = 0.021 and beta = 0.48 [0.01, 0.95] z-score, p = 0.044, respectively) at the distal tibia. Analyses of distal radial and tibial trabecular bone parameters according to diabetic status revealed no significant differences among men or women after adjustment for weight. We found higher cortical porosity and cortical pore volume at the distal tibia in men with DM and higher cortical pore volume at the distal radius in women with a non-significant tendency for higher cortical porosity. The results of our study suggest that deficits in cortical bone exist both in older men and women with DM. PMID- 26686696 TI - A comparison of pediatric gastrostomy tube placement techniques. AB - PURPOSE: This study aimed to compare different techniques for placement of gastrostomy tubes in a pediatric population. STUDY DESIGN: A retrospective review was performed for patients less than 18 years of age who underwent gastrostomy tube placement at a single academic children's hospital between 2010 and 2012. Techniques for gastrostomy placement included Open Stamm, percutaneous endoscopic gastrostomy (PEG), fluoroscopy guided, laparoscopic, and laparoscopic assisted PEG. Pre-operative characteristics of patients and post-operative outcomes were compared between techniques. RESULTS: Most patients underwent an Open Stamm (43 %) or PEG (39 %). There were significant differences between groups with respect to primary diagnoses, prior surgeries, and ASA classification. Major complications were rare, with less than 3 % requiring reoperation within 30 days; however, minor complications and returns to the emergency department were common. Unintentional tube dislodgements occurred in 22 % of all patients, with Open Stamm technique identified as an independent predictor of unintentional dislodgement (p < 0.0001). CONCLUSIONS: Although conclusions from this retrospective analysis are limited due to heterogeneity between groups, open Stamm gastrostomy placement in children was associated with increased negative outcomes including unintentional tube dislodgements, returns to the emergency department, and need for reoperation within 30 days. Prospective analysis of the various techniques is needed to confirm that minimally invasive techniques for gastrostomy tube placement are associated with a less complicated post-operative course. PMID- 26686697 TI - Performance on the Boston Naming Test in Bilinguals. AB - OBJECTIVES: We examined performance on the Boston Naming Test (BNT) in older and younger adults who were monolingual English or French speakers, or bilingual speakers of English and French (n=215). METHODS: Monolingual participants completed the task in their native language, and bilingual participants completed the task in English, French, and bilingual (either-language) administrations. RESULTS: Overall, younger and older monolingual French speakers performed worse than other groups; bilingual participants performed worst in the French administration and approximately two-thirds of bilingual participants performed better when responses were accepted in either language. Surprisingly, however, a subset of bilinguals performed worse when responses were accepted in either language as compared to their maximum score achieved in either English or French. This either-language disadvantage does not appear to be associated with the degree of balanced bilingualism, but instead appears to be related to overall naming abilities. Differential item analysis comparing language groups and the different administrations identified several items that displayed uniform and/or non-uniform differential item functioning (DIF). CONCLUSIONS: The BNT does not elicit equivalent performance in English and French, even when assessing naming performance in monolingual French speakers using the French version of the test. Scores were lower in French overall, and several items exhibited DIF. We recommend caution in interpreting performance on these items in bilingual speakers. Finally, not all bilinguals benefit from an either-language administration of the BNT. PMID- 26686698 TI - Novel techniques in stress echocardiography: a focus on the advantages and disadvantages. AB - Stress echocardiography (SE) is an established tool not only for the assessment of coronary artery disease (CAD), but also for the evaluation of valvular disease and cardiomyopathy. New techniques, namely contrast echocardiography for function and perfusion including assessment of coronary flow reserve, strain imaging, 3 dimensional echocardiography, Doppler-derived coronary flow reserve and multimodality echocardiography, have been incorporated into stress protocols for improving assessment of cardiac disease. In this review, the advantages and disadvantages of these novel SE techniques are examined in terms of feasibility, accuracy, reproducibility and applications. PMID- 26686699 TI - Characteristics of cultured desmoid cells with different CTNNB1 mutation status. AB - Desmoid tumors are benign mesenchymal neoplasms with a locally aggressive nature. The mutational status of beta-catenin gene (CTNNB1) is presumed to affect the tumorous activity of the cells. In this study, we isolated three kinds of desmoid cell with different CTNNB1 status, and compared their characteristics. Cells were isolated from three patients with abdominal wall desmoid during surgery, all of which were resistant to meloxicam treatment. The mutational status of the CTNNB1 exon 3 was determined for both parental tumor tissues and isolated cultured cells. beta-catenin expression was determined with immunohistochemistry. Responsiveness to meloxicam was investigated with MTS assay together with COX-2 immunostaining. mRNA expressions of downstream molecules of Wnt/beta-catenin pathway were determined with real-time RT-PCR. Three kinds of cell isolated from desmoid tumors harboring different CTNNB1 mutation status (wild type, T41A, and S45F), all exhibited a spindle shape. These isolated cells could be cultured until the 20th passage with unchanged proliferative activity. Nuclear accumulation of beta-catenin was observed in all cultured cells, particularly in those with S45F. Proliferating activity was significantly suppressed by meloxicam (25 MUmol/L, P < 0.007) in all three cell cultures, of which parental desmoid was resistant to meloxicam clinically. The mRNA expressions of Axin2, c-Myc, and Cyclin D1 differently increased in the three cultured cell types as compared with those in human skin fibroblast cells (HDF). Inhibitors of Wnt/beta-catenin pathway downregulated Axin2, c-Myc, and Cyclin D1 significantly. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1. PMID- 26686700 TI - Transabdominal Insonation of Fetal Basilar Artery: A Feasibility Study. AB - BACKGROUND: Fetal anterior, middle, and posterior cerebral arteries have been studied using transabdominal Doppler ultrasound. We performed a feasibility study to determine whether basilar artery can be identified and blood flow velocities measured using transabdominal fetal Doppler ultrasound. METHODS: The basilar artery was identified in sagittal plane behind the clivus bone using directional color Doppler with 6-2 and 7-4 MHz curved array probes. The clivus was identified by hyperechoic linear signal anterior to junction of vertebral processes and occipital bone and superior to first vertebral body. The flow direction was away from the probe in the basilar artery consistent with caudo cephalic orientation. The Doppler ultrasound probe was placed at insonation angles of less than 30 degrees at the visualized segment of the basilar artery. Peak systolic and end diastolic velocities were measured. RESULTS: We attempted insonation of the basilar artery in 20 fetuses. The basilar artery was adequately insonated in 18 fetuses with a mean gestational age of 27 weeks (range 19 to 38 weeks). The mean value (+/-SD) of peak systolic velocity of the basilar artery was 22.1 +/- 8.5 cm/second (range 10.4-36.7 cm/second). The mean value (+/-SD) of end diastolic velocity was 6.8 +/- 2.8 cm/second (range 3.5-13.5 cm/second). There was an increase in peak systolic velocity values according to gestational age of fetus. CONCLUSIONS: We demonstrate the feasibility of fetal basilar artery insonation using directional color Doppler ultrasound via transabdominal approach. PMID- 26686701 TI - Vive la difference! Dissecting the diversity of midbrain dopamine neurons. PMID- 26686702 TI - Warfarin-induced intramural haematoma of small bowel. PMID- 26686703 TI - Reproductive technologies combine well with genomic selection in dairy breeding programs. AB - The objective of the present study was to examine whether genomic selection of females interacts with the use of reproductive technologies (RT) to increase annual monetary genetic gain (AMGG). This was tested using a factorial design with 3 factors: genomic selection of females (0 or 2,000 genotyped heifers per year), RT (0 or 50 donors selected at 14 mo of age for producing 10 offspring), and 2 reliabilities of genomic prediction. In addition, different strategies for use of RT and how strategies interact with the reliability of genomic prediction were investigated using stochastic simulation by varying (1) number of donors (25, 50, 100, 200), (2) number of calves born per donor (10 or 20), (3) age of donor (2 or 14 mo), and (4) number of sires (25, 50, 100, 200). In total, 72 different breeding schemes were investigated. The profitability of the different breeding strategies was evaluated by deterministic simulation by varying the costs of a born calf with reproductive technologies at levels of ?500, ?1,000, and ?1,500. The results confirm our hypothesis that combining genomic selection of females with use of RT increases AMGG more than in a reference scheme without genomic selection in females. When the reliability of genomic prediction is high, the effect on rate of inbreeding (DeltaF) is small. The study also demonstrates favorable interaction effects between the components of the breeder's equation (selection intensity, selection accuracy, generation interval) for the bull dam donor path, leading to higher AMGG. Increasing the donor program and number of born calves to achieve higher AMGG is associated with the undesirable effect of increased DeltaF. This can be alleviated, however, by increasing the numbers of sires without compromising AMGG remarkably. For the major part of the investigated donor schemes, the investment in RT is profitable in dairy cattle populations, even at high levels of costs for RT. PMID- 26686704 TI - The effect of paratuberculosis on milk yield--A systematic review and meta analysis. AB - Bovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis. Substantial between-study heterogeneity was observed. Subgroup analysis by case definition and study design was carried out to investigate heterogeneity. The majority of between-study variation was attributed to studies that defined cases on serology. Calculation of a pooled effect estimate was only appropriate for studies that defined cases by organism detection. A reduction in milk yield, corrected for lactation number and herd of origin of 1.87 kg/d, equivalent to 5.9% of yield, was associated with fecal culture or PCR positivity in individual cows. PMID- 26686705 TI - Effect of adjusted pH prior to ultrafiltration of skim milk on membrane performance and physical functionality of milk protein concentrate. AB - Processing conditions during ultrafiltration of skim milk influence properties of the casein micelle and thereby the physical properties of milk protein concentrate (MPC). The aim of the study was to establish the effects of pH adjustment of skim milk feed to obtain MPC with desired emulsification properties. The ultrafiltration was conducted using commercially pasteurized skim milk with the pH adjusted to 6.7 (control), 6.3, 5.9, or 5.5 at 15 degrees C until a volume concentration factor of 5 was reached. Effects of pH adjustment on selected physico-chemical properties (Ca content, particle size, zeta-potential) and functionalities (solubility, heat stability, emulsification capacity, and stability) of MPC were determined. Lowering the feed pH solubilized colloidal calcium phosphate that substantially contributed to modifying the properties of casein. This caused a reduction in the particle size while increasing the net negative charge. The structural modifications in proteins were manifested in the Fourier transform infrared spectra. Subsequent concentration did not induce any further protein structural changes. Such modifications to the casein micelles and colloidal calcium phosphate negatively affected the solubility and heat stability of the corresponding MPC powders. However, the emulsion activity index improved only until the pH of the feed was lowered to 5.9 and declined when pH was dropped to 5.5, followed with the loss of stability. Readjusting the pH of MPC powder dispersions to 6.7 restored their surface properties and thereby their functionality. Lowering the feed pH also negatively affected the membrane performance by clogging the membrane pores and lowering the flux, particularly at pH 5.5. Adjusting pH to 5.9 produced MPC with optimum emulsifying properties with minimal influence on membrane performance. PMID- 26686706 TI - Economic impact of nutritional grouping in dairy herds. AB - This article evaluates the estimated economic impact of nutritional grouping in commercial dairy herds using a stochastic Monte Carlo simulation model. The model was initialized by separate data sets obtained from 5 commercial dairy herds. These herds were selected to explore the effect of herd size, structure, and characteristics on the economics and efficiency of nutrient usage according to nutritional grouping strategies. Simulated status of each cow was updated daily together with the nutrient requirements of net energy for lactation (NEL) and metabolizable protein (MP). The amount of energy consumed directly affected body weight (BW) and body condition score (BCS) changes. Moreover, to control the range of observed BCS in the model, constraints on lower (2.0) and upper (4.5) bounds of BCS were set. Each month, the clustering method was used to homogeneously regroup the cows according to their nutrient concentration requirements. The average NEL concentration of the group and a level of MP (average MP, average MP+0.5SD, or average MP+1SD) were considered to formulate the group diet. The calculated income over feed costs gain (IOFC, $/cow per yr) of having >1 nutritional group among the herds ranged from $33 to $58, with an average of $39 for 2 groups and $46 for 3 groups, when group was fed at average NEL concentration and average MP+1SD concentration. The improved IOFC was explained by increased milk sales and lower feed costs. Higher milk sales were a result of fewer cows having a milk loss associated with low BCS in multi-group scenarios. Lower feed costs in multi-group scenarios were mainly due to less rumen-undegradable protein consumption. The percentage of total NEL consumed captured in milk for >1 nutritional group was slightly lower than that for 1 nutritional group due to better distribution of energy throughout the lactation and higher energy retained in body tissue, which resulted in better herd BCS distribution. The percentage of fed N captured in milk increased with >1 group and was the most important factor for improved economic efficiency of grouping strategies. PMID- 26686707 TI - Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis. AB - The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-alpha receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1 changed in SCAT and RPAT during the considered time period. For the HCAR2 protein, time-dependent changes were restricted to SCAT. The mRNA abundance of all receptors was greater in RPAT than in SCAT. The tissue-specific correlations observed between the receptors point to a link between these factors and may indicate different regulatory roles in the respective tissues. This study provides insight into the complex metabolic adaptations during the transition period and supports a differential regulation of lipolysis among SCAT and RPAT in dairy cows. PMID- 26686708 TI - Field validation of protocols developed to evaluate in-line mastitis detection systems. AB - This paper reports on a field validation of previously developed protocols for evaluating the performance of in-line mastitis-detection systems. The protocols outlined 2 requirements of these systems: (1) to detect cows with clinical mastitis (CM) promptly and accurately to enable timely and appropriate treatment and (2) to identify cows with high somatic cell count (SCC) to manage bulk milk SCC levels. Gold standard measures, evaluation tests, performance measures, and performance targets were proposed. The current study validated the protocols on commercial dairy farms with automated in-line mastitis-detection systems using both electrical conductivity (EC) and SCC sensor systems that both monitor at whole-udder level. The protocol for requirement 1 was applied on 3 commercial farms. For requirement 2, the protocol was applied on 6 farms; 3 of them had low bulk milk SCC (128*10(3) cells/mL) and were the same farms as used for field evaluation of requirement 1. Three farms with high bulk milk SCC (270*10(3) cells/mL) were additionally enrolled. The field evaluation methodology and results were presented at a workshop including representation from 7 international suppliers of in-line mastitis-detection systems. Feedback was sought on the acceptance of standardized performance evaluation protocols and recommended refinements to the protocols. Although the methodology for requirement 1 was relatively labor intensive and required organizational skills over an extended period, no major issues were encountered during the field validation of both protocols. The validation, thus, proved the protocols to be practical. Also, no changes to the data collection process were recommended by the technology supplier representatives. However, 4 recommendations were made to refine the protocols: inclusion of an additional analysis that ignores small (low density) clot observations in the definition of CM, extension of the time window from 4 to 5 milkings for timely alerts for CM, setting a maximum number of 10 milkings for the time window to detect a CM episode, and presentation of sensitivity for a larger range of false alerts per 1,000 milkings replacing minimum performance targets. The recommended refinements are discussed with suggested changes to the original protocols. The information presented is intended to inform further debate toward achieving international agreement on standard protocols to evaluate performance of in-line mastitis-detection systems. PMID- 26686709 TI - Comparison of transmission dynamics between Streptococcus uberis and Streptococcus agalactiae intramammary infections. AB - The objectives of study were to determine the transmission parameters (beta), durations of infection, and basic reproductive numbers (R0) of both Streptococcus agalactiae and Streptococcus uberis as pathogens causing mastitis outbreaks in dairy herds. A 10-mo longitudinal study was performed using 2 smallholder dairy herds with mastitis outbreaks caused by Strep. agalactiae and Strep. uberis, respectively. Both herds had poor mastitis control management and did not change their milking management during the entire study period. Quarter milk samples were collected at monthly intervals from all lactating animals in each herd for bacteriological identification. The durations of infection for Strep. uberis intramammary infection (IMI) and Strep. agalactiae IMI were examined using Kaplan Meier survival curves, and the Kaplan-Meier survival functions for Strep. uberis IMI and Strep. agalactiae IMI were compared using log rank survival-test. The spread of Strep. uberis and Strep. agalactiae through the population was determined by transmission parameter, beta, the probability per unit of time that one infectious quarter will infect another quarter, assuming that all other quarters are susceptible. For the Strep. uberis outbreak herd (31 cows), 56 new infections and 28 quarters with spontaneous cure were observed. For the Strep. agalactiae outbreak herd (19 cows), 26 new infections and 9 quarters with spontaneous cure were observed. The duration of infection for Strep. agalactiae (mean=270.84 d) was significantly longer than the duration of infection for Strep. uberis (mean=187.88 d). The transmission parameters (beta) estimated (including 95% confidence interval) for Strep. uberis IMI and Strep. agalactiae IMI were 0.0155 (0.0035-0.0693) and 0.0068 (0.0008-0.0606), respectively. The R0 (including 95% confidence interval) during the study were 2.91 (0.63-13.47) and 1.86 (0.21-16.61) for Strep. uberis IMI and Strep. agalactiae IMI, respectively. In conclusion, the transmission parameter and R0 values were not different between both pathogens; however, the duration of infection for Strep. agalactiae was longer than Strep. uberis. These suggest that Strep. uberis may have a different transmission dynamic compared with Strep. agalactiae. PMID- 26686710 TI - Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 2: The SIRT-PPARGC1A axis and its relationship with the adiponectin system. AB - The transition period in dairy cows is characterized by major changes in glucose and adipose tissue metabolism. The Sirtuin-1 (SIRT1) PPARgamma co-activator 1alpha (PPARGC1A) axis might be related to the adiponectin (ADIPOQ) system to orchestrate the regulation of these processes. We aimed to assess the mRNA abundance of the aforementioned components in one visceral and one subcutaneous fat depot, together with the ADIPOQ concentrations in serum of dairy cows from late gestation to early lactation. In addition, the effect of 2 diets differing in energy density was tested. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum. From then on until d 1 antepartum, 10 animals each were assigned to either high-concentrate (60:40 concentrate:roughage) or low-concentrate (30:70) diets. Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d nicotinic acid from d -42 until d 24. From d 1 postpartum (p.p.) to d 24 p.p., the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d 42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies as well as on d -21, -14, -7, -3, 1, 3, 7, 14, 21, 28, 35, 42, 63, 82, and 100 relative to calving. Quantification of target mRNA was done using quantitative PCR and serum ADIPOQ concentration was measured via ELISA. The feeding regimen did not affect the variables examined. Serum ADIPOQ concentrations decreased toward parturition, returned to precalving levels within 1 wk after parturition, and remained on a constant level until the end of the experiment. The mRNA abundance of SIRT1, PPARGC1A, NAMPT, and the ADIPOQ receptors 1 (ADIPOR1) and 2 (ADIPOR2) changed in SCAT and RPAT during the considered time period. Comparing SCAT and RPAT, the mRNA of SIRT1, ADIPOR1, and ADIPOR2 were more abundant in RPAT, whereas PPARGC1A and NAMPT were expressed more highly in SCAT. The protein abundance of SIRT1 tended to increase from d -42 to 21. At d 21 we detected more PPARGC1A protein in the low-concentrate group as compared with the high-concentrate group. The correlations observed point to a link between these factors and might hint to a functional role of the variables in the regulation of glucose metabolism. This study substantiates the existence of the SIRT1-PPARGC1A-axis and indicates a functional relationship between SIRT1 and ADIPOR1 in bovine adipose tissue. PMID- 26686711 TI - Managing complexity: Dealing with systemic crosstalk in bovine physiology. AB - Dairy producers rely heavily on advisors with deep expertise in nutrition, reproduction, and health. However, a shift is occurring, driven both by farm size and by advances in biology. Larger dairy businesses can investigate management options with a degree of precision never before possible; simultaneously, the lines between the metabolic, immune, and reproductive systems are becoming blurred. For example, new research has revealed a surprising role for immune cells in regulating metabolism and documented the nutrient requirements of the immune system. The gut epithelium has garnered new attention as a tissue that actively manages the commensal microbiome, entrains the responses of the neonatal immune system, and provides a barrier limiting movement of molecules from the gut lumen. New hormone discoveries have added adipose tissue, bone, and muscle to the list of endocrine organs. Finally, nutrients are now seen not only as substrates and cofactors, but also as signals that can alter cellular function. What does all of this mean for the dairy industry? Consultants are increasingly reaching across disciplinary boundaries to best support the physiology of the cow. However, research is needed to translate proof-of-principle findings into applications in cattle. Key unanswered questions include the degree to which roles of the hindgut in monogastrics translate to ruminants, and whether some host-microbe crosstalk also occurs in the rumen; whether hormone release by storage organs during a catabolic state affects reproductive function; and the degree to which immunostimulation by dietary signals enhances or disrupts health and productivity. It is critical to address these questions with multiple approaches. Mechanistic studies provide a nuanced understanding of signal interactions, but large-scale commercial studies are needed to evaluate effects on multiple production outcomes in the environment of interest, and meta-analyses best integrate findings into a cohesive understanding of responses to diet. Incorporating all aspects of animal health and productivity in management decisions will remain an art for the foreseeable future, but this should not dissuade the industry from pursuing a more holistic approach to management of the cow. PMID- 26686712 TI - Short communication: Removal of hair from the mammary gland: Recovery of bacteria from teat skin and milk. AB - It has been assumed that the presence of udder hair can interfere with safe milking practices and reduce the wholesomeness of milk relative to bacterial content. This study determined the effect of removal by singeing udder hair on the microflora of teat skin (total bacteria, coliform, and esculin-positive and esculin-negative streptococci) and milk (total bacteria, coliform, psychrotrophic, and thermoduric counts) as opposed to not singeing udder hair, using different pre-and postmilking disinfection (predip, postdip, or both) combinations. The 4 different pre-and postmilking disinfection combinations were predip and postdip, postdip only, predip only, and no predip and no postdip. Differences in bacterial numbers recovered from teat skin and milk in singed and not singed glands were not significantly affected by treatment. Findings of this trial do not support the concept that udder hair removal results in improved milk quality as measured by bacterial content. PMID- 26686713 TI - Management practices associated with presence of Staphylococcus aureus in bulk tank milk from Ohio dairy herds. AB - Staphylococcus aureus is the most common contagious mastitis pathogen affecting cows worldwide. Practices to control this organism have been advocated for decades, and identification of risk factors in individual herds is crucial in prevention and control of Staph. aureus. The objectives of this paper were to estimate prevalence of Staph. aureus in Ohio dairies and to determine a potential association of herd characteristics and management practices with isolation of Staph. aureus in bulk tank milk. A questionnaire about herd characteristics, milking procedures, udder health, mastitis control, and biosecurity practices was mailed to 780 dairy producers; the response rate for the survey was 49%. Staphylococcus aureus prevalence was 48, 64, and 69% when 1, 2, or 3 samples of bulk tank milk from each herd were considered, respectively. Herds practicing prestrip, pre- and postmilking teat dip, and using a single towel per cow as part of the milking routine as well as herds where owners were involved in milking were at significantly reduced odds for detection of Staph. aureus in their bulk tank milk. PMID- 26686714 TI - Short communication: Effect of canola meal use as a protein source in a starter mixture on feeding behavior and performance of calves during the weaning transition. AB - The aim of this study was to determine the effect of canola meal use as a protein source in a starter mixture (SM) on feeding behavior and performance of calves during weaning transition. A total of 36 female Holstein calves of a mean age 14.9+/-1.6 d and body weight 40.1+/-4.2 kg (mean +/- SD) were allocated to 1 of 3 treatments differing in the main source of protein for the SM (12 calves per treatment): (1) soybean meal (TSBM); (2) soybean meal and canola meal (TSBM/TCM); and (3) canola meal (TCM). The SM was offered for ad libitum consumption beginning on the first day of the study, whereas milk replacer (MR) was fed in amounts equal to 900 g (as fed) per day from d 1 to 35 and 450 g/d from d 36 to 42 of the study. Calves were completely weaned on d 43 of the study (57.9+/-1.6 d of age; mean +/- SD), and their performance was monitored for an additional 2 wk. Calf body weight was recorded weekly, and MR and SM intake and fecal fluidity were recorded daily. Feeding behavior of calves during weaning transition, including frequency (no./d), time (min/d), and rate (g/min) of eating the SM as well as frequency and time of drinking water, was monitored on 6 calves per treatment for 2 consecutive days before MR step-down (d 34-35), at MR step-down (d 41-42), and after weaning (d 48-49 of study). Starter mixture intake tended to be higher for TSBM calves as compared with TSBM/TCM calves from d 1 to 35 of the study but was not different between TSBM and TCM calves and was not different between treatments in the whole study period. Calves from TCM treatment had reduced average daily gain (ADG) and feed efficiency (g of ADG/kg of dry matter intake) and a higher fecal score in the period from d 1 to 35 of the study and had lower feed efficiency and tended to have lower ADG in the whole study period as compared with TSBM calves. Average daily gain and feed efficiency did not differ between TSBM and TSBM/TCM calves. Frequency of eating the SM and drinking water as well as time and rate of eating the SM and time of drinking water did not differ between treatments. It is concluded that presence of canola meal in a SM does not affect feeding behavior and performance of calves during weaning transition but has a negative effect on ADG, feed efficiency, and number of days with diarrhea during the preweaning phase of rearing. PMID- 26686715 TI - Detection of viable enterotoxin-producing Bacillus cereus and analysis of toxigenicity from ready-to-eat foods and infant formula milk powder by multiplex PCR. AB - Bacillus cereus is responsible for several outbreaks of foodborne diseases due to its emetic toxin and enterotoxin. Enterotoxins, cytotoxin K (CytK), nonhemolytic enterotoxin (Nhe), and hemolysin BL (Hbl), have been recorded in several diarrheal cases due to food poisoning from B. cereus. The objective of this study was to develop a rapid and accurate method that combines multiplex PCR with propidium monoazide to selectively detect viable cells of enterotoxin-producing B. cereus in milk powder, noodles, and rice, and investigate the distribution of enterotoxins in 62 strains of B. cereus in Jiangxi province, China. The specificity of primers of 3 enterotoxins (i.e., cytK, nheA, and hblD) of B. cereus was verified by inclusivity and exclusivity tests using single PCR. Upon optimization of multiplex PCR conditions, it was found that the detection limit of viable cells was 10(2) cfu/mL of B. cereus in pure culture. By enrichment for 3 or 4 h and propidium monoazide pretreatment, a protocol for detection of viable cells as low as 2.2*10(1) cfu/g in spiked food (e.g., milk powder, noodles, and rice) was established and proved valid even under the interference of non Bacillus cereus at as high as 10(5) cfu/g. Moreover, the protocol based on multiplex PCR for detection was applied for the analysis of distribution of toxin gene of B. cereus, and the results showed a regional feature for toxin gene distribution, indicating that potential toxigenicity of B. cereus should be evaluated further. PMID- 26686716 TI - Evaluation of calving indicators measured by automated monitoring devices to predict the onset of calving in Holstein dairy cows. AB - Dystocias are common in dairy cows and often adversely affect production, reproduction, animal welfare, labor, and economics within the dairy industry. An automated device that accurately predicts the onset of calving could potentially minimize the effect of dystocias by enabling producers to intervene early. Although many well-documented indicators can detect the imminence of calving, research is limited on their effectiveness to predict calving when measured by automated devices. The objective of this experiment was to determine if a decrease in vaginal temperature (VT), rumination (RT), and lying time (LT), or an increase in lying bouts (LB), as measured by 3 automated devices, could accurately predict the onset of calving within 24, 12, and 6 h. The combination of these 4 calving indicators was also evaluated. Forty-two multiparous Holstein cows housed in tie-stalls were fitted with a temperature logger inserted in the vaginal cavity 7+/-2 d before their expected calving date; VT was recorded at 1 min intervals. An ear-attached sensor recorded rumination time every hour based on ear movement while an accelerometer fitted to the right hind leg recorded cow position at 1-min intervals. On average, VT were 0.3+/-0.03 degrees C lower, and RT and LT were 41+/-17 and 52+/-28 min lower, respectively, on the calving day compared with the previous 4 d. Cows had 2+/-1 more LB on the calving day. Of the 4 indicators, a decrease in VT>=0.1 degrees C was best able to predict calving within the next 24 h with a sensitivity of 74%, specificity of 74%, positive and negative predictive values of 51 and 89%, and area under the curve of 0.80. Combining the indicators enhanced the performance to predict calving within the next 24, 12, and 6 h with best overall results obtained by combining the 3 devices for prediction within the next 24 h (sensitivity: 77%, specificity: 77%, positive and negative predictive values: 56 and 90%, area under the curve: 0.82). These results indicate that a device that could simultaneously measure these 4 calving indicators could not precisely determine the onset of calving, but the information collected would assist dairy farmers in monitoring the onset of calving. PMID- 26686717 TI - Short communication: Ultrasonographic assessment of lung consolidation postweaning and survival to the first lactation in dairy heifers. AB - The aim of this prospective cohort study was to assess the association of systematic thoracic ultrasonography findings postweaning on calves' survivability to the first lactation. Three-month-old Jersey heifers (n=250) returning from a custom heifer grower were scanned by thoracic ultrasonography and lungs assessed using a scoring system with a scale from 1 to 4. A score of 1 was attributed to calves with no abnormality. A score of 2 was assigned if multiple comet tails or B-lines (coalescence of multiple comet tails) were observed. A score of 3 was assigned to calves with >=1 location of lung consolidation >=1 cm but <6 cm. Calves with extensive consolidation (>=6 cm in one or more locations) or evidence of abscessation or pleural effusion (>1 cm) were assigned a score of 4. Calves with a score of 4 had greater risk of dying or being culled [26% (95% credibility interval: 13-47%)] than calves with a score of 1 [1% (0-6%)], 2 [3% (1-9%)], or 3 [5% (1-17%)]. We found no association between age of first calving in the remaining calves and lung score. Thus, lung lesion severity assessed by thoracic ultrasound is associated with a long-term production outcome. PMID- 26686718 TI - A model of milk production in lactating dairy cows in relation to energy and nitrogen dynamics. AB - A generic daily time-step model of a dairy cow, designed to be included in whole system pasture simulation models, is described that includes growth, milk production, and lactation in relation to energy and nitrogen dynamics. It is a development of a previously described animal growth and metabolism model that describes animal body composition in terms of protein, water, and fat, and energy dynamics in relation to growth requirements, resynthesis of degraded protein, and animal activity. This is further developed to include lactation and fetal growth. Intake is calculated in relation to stage of lactation, pasture availability, supplementary feed, and feed quality. Energy costs associated with urine N excretion and methane fermentation are accounted for. Milk production and fetal growth are then calculated in relation to the overall energy and nitrogen dynamics. The general behavior of the model is consistent with expected characteristics. Simulations using the model as part of a whole-system pasture simulation model (DairyMod) are compared with experimental data where good agreement between pasture, concentrate and forage intake, as well as milk production over 3 consecutive lactation cycles, is observed. The model is shown to be well suited for inclusion in large-scale system simulation models. PMID- 26686719 TI - Consumers' behavior in quantitative microbial risk assessment for pathogens in raw milk: Incorporation of the likelihood of consumption as a function of storage time and temperature. AB - Foodborne disease as a result of raw milk consumption is an increasing concern in Western countries. Quantitative microbial risk assessment models have been used to estimate the risk of illness due to different pathogens in raw milk. In these models, the duration and temperature of storage before consumption have a critical influence in the final outcome of the simulations and are usually described and modeled as independent distributions in the consumer phase module. We hypothesize that this assumption can result in the computation, during simulations, of extreme scenarios that ultimately lead to an overestimation of the risk. In this study, a sensorial analysis was conducted to replicate consumers' behavior. The results of the analysis were used to establish, by means of a logistic model, the relationship between time-temperature combinations and the probability that a serving of raw milk is actually consumed. To assess our hypothesis, 2 recently published quantitative microbial risk assessment models quantifying the risks of listeriosis and salmonellosis related to the consumption of raw milk were implemented. First, the default settings described in the publications were kept; second, the likelihood of consumption as a function of the length and temperature of storage was included. When results were compared, the density of computed extreme scenarios decreased significantly in the modified model; consequently, the probability of illness and the expected number of cases per year also decreased. Reductions of 11.6 and 12.7% in the proportion of computed scenarios in which a contaminated milk serving was consumed were observed for the first and the second study, respectively. Our results confirm that overlooking the time-temperature dependency may yield to an important overestimation of the risk. Furthermore, we provide estimates of this dependency that could easily be implemented in future quantitative microbial risk assessment models of raw milk pathogens. PMID- 26686720 TI - Effect of housing type on health and performance of preweaned dairy calves during summer in Florida. AB - The objective was to evaluate the effect of housing type on health and performance of preweaned dairy calves. One hundred calves, Holsteins (HO) or Holstein-Jersey crosses (HJ), were randomly assigned to a Calf-Tel (L. T. Hampel Corp., Germantown, WI) polyethylene hutch exposed to direct sun light (n=25 for both HO and HJ) or a wire hutch with a plywood shade located under trees (n=24 and 26 for HO and HJ, respectively). Calf rectal temperature, respiratory rate, health scores, and weaning weight were compared by housing type. Rectal temperatures were higher in calves in Calf-Tel hutches compared with calves in wire hutches at 1500 h, at 40.1+/-0.28 and 39.1+/-0.22 degrees C, respectively. Similarly, respiratory rates were higher in calves in Calf-Tel hutches compared with calves in wire hutches at 1500 h, at 90+/-15 and 65+/-10 breaths per minute, respectively. Frequencies of calves presenting abnormal ear scores did not differ between calves in Calf-Tel or wire hutches. Abnormal eye scores were less likely to occur for calves in the wire hutches. Frequencies of calves with signs of respiratory disease, such as nasal discharge and coughing, were higher in the wire hutches compared with the Calf-Tel hutches. No differences were noted in the incidence and time of first diarrhea event in calves between hutch types. Calves in wire hutches had 5.47 greater odds of receiving veterinary treatment compared with calves in the Calf-Tel hutches. Weaning weights were not different for calves in Calf-Tel or in wire hutches. The lower frequency of calves with abnormal health scores and receiving veterinary treatment in Calf-Tel hutches and the lack of difference in weight gain suggests that this housing system adapted well to the specific environmental conditions of this study. PMID- 26686721 TI - The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows. AB - Longitudinal data from 3 commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Mycobacterium avium ssp. paratuberculosis (MAP) infection status and progression path on milk production. Disease status, as indicated by MAP test results, was determined through quarterly ELISA serum testing, biannual fecal culture, and culture of tissues and feces at slaughter. Milk production data were collected from the Dairy Herd Information Association. Animals with positive MAP test results were categorized, based on test results over the full course of the study, as high path (at least one high-positive culture) or low path (at least one positive culture or ELISA). The cumulative numbers of positive ELISA and culture results were recorded. The effects of both MAP infection path, status, and number of positive tests on milk production were analyzed using a mixed linear model with an autocorrelation random effect structure. Low- and high-path animals produced more milk before their first positive test than always-negative animals, especially high-path animals. Although mean production decreased after a first positive test, low-path animals were shown to recover some productivity. High-path animals continued to exhibit a decrease in milk production, especially after their first high-positive fecal culture. These results show that not all animals that test positive for MAP will have long-term production losses. Milk production decreased significantly with each additional positive test. Ultimately, production loss appeared to be a function of MAP infection progression. PMID- 26686722 TI - Effect of social housing on the development of feeding behavior and social feeding preferences of dairy calves. AB - This study investigated how social housing affects pre- and postweaning feeding behavior and social feeding preferences of dairy calves. Twenty Holstein bull calves were housed either individually (IH; 10 calves) or in pairs (PH; 10 calves) from birth. Calves were offered grain concentrate and milk replacer ad libitum via an artificial teat (1 teat provided per calf) and weaned by incrementally diluting the milk replacer from 39 to 49 d of age. Postweaning, IH calves were paired within treatment and all pens (n=5 per treatment) were offered a complete pelleted diet ad libitum and followed until 13 wk of age. We recorded feeding times from video for 3 consecutive days in wk 6, 9, and 12 of age and used this to calculate daily meal frequency and meal duration. In wk 9 and 12, frequency and duration of synchronized feeding were also calculated. In addition, preference tests were conducted at time of feed delivery in wk 10 to assess the preference of each calf to feed alongside or out of visual contact of their pen mate. Pair-housed calves consumed more concentrate, in more frequent meals, than IH calves in the week before weaning (wk 6) and continued to have greater concentrate intake during weaning. Milk intake was not affected by treatment, but calves in PH pens consumed their milk in more frequent and smaller meals. Postweaning, intake was similar between treatments, but calves raised in PH pens continued to have meals that were more frequent and shorter in duration. Both treatments had a similar frequency of synchronized meals. However, when offered a choice to feed alone or alongside their pen mate during preference testing, calves raised in PH pens spent more time feeding in the presence of their pen mate than calves raised in IH pens. These results suggest that meal patterns established in response to different early social environments may persist after weaning and that early social contact may have longer-term effects on social feeding behavior. PMID- 26686723 TI - Implications of PCR and ELISA results on the routes of bulk-tank contamination with Mycobacterium avium ssp. paratuberculosis. AB - Mycobacterium avium ssp. paratuberculosis (MAP), the etiologic agent of Johne's disease in dairy cattle, may enter the bulk tank via environmental contamination or direct excretion into milk. Traditionally, diagnostics to identify MAP in milk target either MAP antibodies (by ELISA) or the organism itself (by culture or PCR). High ELISA titers may be directly associated with excretion of MAP into milk but only indirectly linked to environmental contamination of the bulk tank. Patterns of bulk-milk ELISA and bulk-milk PCR results could therefore provide insight into the routes of contamination and level of infection or environmental burden. Coupled with questionnaire responses pertaining to management, the results of these diagnostic tests could reveal correlations with herd characteristics or on-farm practices that distinguish herds with high and low environmental bulk-tank MAP contamination. A questionnaire on hygiene, management, and Johne's specific parameters was administered to 292 dairy farms in New York, Oregon, and Wisconsin. Bulk-tank samples were collected from each farm for evaluation by real-time PCR and ELISA. Before DNA extraction and testing of the unknown samples, bulk-milk template preparation was optimized with respect to parameters such as MAP fractionation patterns and lysis. Two regression models were developed to explore the relationships among bulk-tank PCR, ELISA, environmental predictors, and herd characteristics. First, ELISA optical density (OD) was designated as the outcome in a linear regression model. Second, the log odds of being PCR positive in the bulk tank were modeled using binary logistic regression with penalized maximum likelihood. The proportion of PCR-positive bulk tanks was highest for New York and for organic farms, providing a clue as to the geographical patterns of MAP-positive bulk-tank samples and relationship to production type. Bulk-milk PCR positivity was also higher for large relative to small herds. The models revealed that bulk-milk PCR result could predict ELISA OD, with PCR-positive results corresponding to high bulk-milk ELISA titers. Similarly, ELISA was a predictor of PCR result, although the association was stronger for organic farms. Despite agreement between high bulk-milk ELISA titers and positive PCR results, a large proportion of high ELISA farms had PCR-negative bulk tanks, suggesting that farms are able to maintain satisfactory hygiene and management despite a presence of MAP in these herds. PMID- 26686724 TI - Metabolome analysis of milk fermented by gamma-aminobutyric acid-producing Lactococcus lactis. AB - gamma-Aminobutyric acid (GABA) is one of the most important functional components in fermented foods because of its physiological functions, such as neurotransmission and antihypertensive activities. However, little is known about components other than GABA in GABA-rich fermented foods. A metabolomic approach offers an opportunity to discover bioactive and flavor components in fermented food. To find specific components in milk fermented with GABA-producing Lactococcus lactis 01-7, we compared the components found in GABA-rich fermented milk with those found in control milk fermented without GABA production using capillary electrophoresis time-of-flight mass spectrometry. A principal component analysis score plot showed a clear differentiation between the control milk fermented with L. lactis 01-1, which does not produce GABA, and GABA-rich milk fermented with a combination of L. lactis strains 01-1 and 01-7. As expected, the amount of GABA in GABA-rich fermented milk was much higher (1,216-fold) than that of the control milk. Interestingly, the amount of Orn was also much higher (27 fold) than that of the control milk. Peptide analysis showed that levels of 6 putative angiotensin-I-converting enzyme (ACE)-inhibitory peptides were also higher in the GABA-rich fermented milk. Furthermore, ACE-inhibitory activity of GABA-rich fermented milk tended to be higher than that of the control milk. These results indicate that the GABA-producing strain 01-7 provides fermented milk with other functional components in addition to GABA. PMID- 26686725 TI - Development of a method to characterize high-protein dairy powders using an ultrasonic flaw detector. AB - Dissolution behavior of high-protein dairy powders plays a critical role for achieving functional and nutritional characteristics of a finished food product. Current methods for evaluating powder dissolution properties are time consuming, difficult to reproduce, and subjective. Ultrasound spectroscopy is a rapid and precise method, but requires expensive equipment and skilled technicians to carry out the tests. In the present study, an ultrasonic flaw detector (UFD) was used as an economical alternative to characterize the powder dissolution properties. The objective of study was to develop a method to characterize the dissolution behavior of milk protein concentrate (MPC) using a UFD. The experimental setup included a UFD connected to a 1-MHz immersion transducer that was kept a constant distance from a reflector plate. To validate the method, 2 batches of MPC80 from a commercial manufacturer were procured and stored at 25 and 40 degrees C for 4 wk. Focus beam reflectance measurement and solubility index were used as reference methods. Relative ultrasound velocity and ultrasound attenuation were acquired during the dissolution of MPC samples. To characterize the MPC dissolution, 4 parameters including standard deviation of relative velocity, area under the attenuation curve, and peak attenuation were extracted from ultrasound data. As the storage temperature and time increased, the area under the attenuation curve and peak height decreased, indicating a loss of solubility. The proposed UFD-based method was able to capture the changes in dissolution of MPC during storage at 25 and 40 degrees C. It was observed that a high-quality MPC had a low standard deviation and a larger area under the attenuation curve. As the MPC aged at 40 degrees C, the particle dispersion rate decreased and, consequently, an increase in standard deviation and reduction in area were observed. Overall, the UFD can be a low-cost method to characterize the dissolution behavior of high-protein dairy powders. PMID- 26686726 TI - Enhanced natural killer cell activation by exopolysaccharides derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1. AB - Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-gamma in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-gamma production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R 1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-gamma knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-gamma production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-gamma production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-gamma inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable. PMID- 26686727 TI - Dietary cation-anion difference and day length have an effect on milk calcium content and bone accretion of dairy cows. AB - Milk and dairy products are an important source of Ca for humans. Recent studies have shown fluctuations in cow milk Ca content during the year in France, with high values in winter and with corn silage diets, and a decrease during May and June and with grass diets. The aim of this study was to identify the reasons for this seasonal decrease in milk Ca content by testing the effect of 2 levels of dietary cation-anion differences (DCAD; 0 mEq/kg of dry matter for DCAD 0 and 400 mEq/kg for DCAD 400) and 2 day lengths (8 h of light/d for short days: SD; and 16 h/d for long days: LD) on the Ca balances of dairy cows. The DCAD treatments were designed to mimic diets based either on corn silage or on herbage. The cows were only illuminated by solarium lights providing UVA and UVB. The trial was conducted according to 2 simultaneous replicates of a 4*4 Latin square design using 8 dairy cows averaging 103+/-44 d in milk with 4 periods of 14 d. Data were analyzed by ANOVA with a model including treatment, cow, and period effects. No significant interaction was found between day length and DCAD treatments. With DCAD 400 compared with DCAD 0, blood pH increased and plasma ionized Ca content decreased, whereas the plasma total Ca content did not differ between treatments. Milk Ca content, however, increased with DCAD 400 compared with DCAD 0, in relation to a decrease in the amount of Ca excreted in urine. The DCAD had no significant effect on protein and casein contents and DCAD 400 tended to decrease milk yield. This illustrates that the udder did not decrease Ca uptake from the blood at high DCAD even though DCAD 400 decreased the mammary availability of Ca by decreasing the proportion of blood ionized Ca. Milk Ca and casein contents were significantly lower with LD compared with SD, whereas day length had no effect on milk yield after 14 d of treatment. Bone accretion of cows increased when the Ca content of milk increased (i.e., with DCAD 400 compared with DCAD 0 and with SD compared with LD). This work suggests that long and sunny days could explain part of the seasonal decrease in milk Ca content in summer and refutes the hypothesis that low milk Ca contents at grazing could be due to the high DCAD of herbage. PMID- 26686728 TI - Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms. AB - Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000 cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM. PMID- 26686729 TI - Replacing cereals with dehydrated citrus pulp in a soybean oil supplemented diet increases vaccenic and rumenic acids in ewe milk. AB - This study evaluates the effect of the replacement of cereals by dried citrus pulp (DCP) in diets supplemented with 5% of soybean oil, on ewe milk yield and composition, including milk fatty acid (FA). Four Serra da Estrela multiparous ewes in the second month of lactation were used in a double 2*2 Latin square design. Ewes were individually penned and milked twice a day with an 8-h interval. Each experimental period included 14 d of diet adaptation followed by 5d of measurements and sampling. The 2 diets included on dry matter basis 450 g/kg of corn silage and 550 g/kg of either a soybean oil-supplemented concentrate meal containing barley and maize (cereal) or dried citrus pulp (DCP; citrus). Feed was offered ad libitum, considering 10% of orts, and intake was measured daily. Milk yield was higher and dry matter intake tended to be higher with the citrus diet. Milk composition and technological properties for cheese production were not affected by treatments, except for lactose, which was lower with the citrus diet. Replacement of cereals by DCP resulted in a 3-percentage-point decrease of both 18:0 and cis-9-18:1 that were mostly compensated by the 4.19- and 1.68-percentage-point increases of trans-11-18:1 and cis-9,trans-11-18:2, respectively. The intake of C18 FA tended to increase with the citrus diet compared with the cereal diet, but the apparent transfer of 18:2n-6 and of 18:3n 3 did not differ between diets. The milk output of C18 FA increased with the citrus compared with the cereal diet, mostly due to the increase of trans-11-18:1 and cis-9,trans-11-18:2 because the daily milk output of 18:0, trans-10-18:1, cis 9-18:1, 18:2n-6 and 18:3n-3 did not differ between diets. Replacing cereals with DCP in an oil-supplemented diet resulted in a selective increase of trans-11-18:1 and cis-9,trans-11-18:2 in milk, with no major effect on other biohydrogenation intermediates. PMID- 26686730 TI - Mitochondrial DNA copy number and biogenesis in different tissues of early- and late-lactating dairy cows. AB - Energy balance in dairy cows changes during the course of lactation due to alterations in voluntary feed intake and energy required for milk synthesis. To adapt to the demands of lactation, energy metabolism needs to be regulated and coordinated in key organs such as adipose tissue (AT), liver, and mammary gland. Mitochondria are the main sites of energy production in mammalian cells and their number varies depending on age, organ, and physiological condition. The copy number of the mitochondrial genome, the mitochondrial DNA (mtDNA), reflects the abundance of mitochondria within a cell and is regulated by transcriptional and translational factors. Environmental, physiological, and energetic conditions change during lactation and we thus hypothesized that these changes may influence the mtDNA copy number and the abundance of genes regulating mitochondrial biogenesis. Therefore, we aimed to provide an overview of mitochondrial biogenesis in liver, subcutaneous (sc)AT, mammary gland, and peripheral blood cells during early and late lactation in dairy cows. German Holstein cows (n=21) were fed according to their requirements, and biopsies from scAT, liver, mammary gland, and blood were collected in early and late lactation and assayed for relative mtDNA copy numbers and the mRNA abundance of genes regulating mitochondrial biogenesis, such as nuclear-respiratory factor 1 and 2 (NRF-1, NRF 2), mitochondrial transcription factor A (TFAM), and peroxisome proliferator activated receptor-gamma coactivator 1-alpha (PGC-1alpha). The number of mtDNA copies increased from early to late lactation in all tissues, whereas that in peripheral blood cells was greater in early compared with late lactation. Moreover, mitochondrial activity enzymes (i.e., citrate synthase and cytochrome c oxidase) increased from early to late lactation in scAT. Comparing the number of mtDNA copies between tissues and blood in dairy cows, the highest mtDNA content was observed in liver. The mRNA abundance of genes related to mitochondrial biogenesis changed in a tissue-specific manner when comparing early versus late lactation. The mtDNA copy number was associated with transcriptional factors only in AT, suggesting nontranscriptional regulation of mtDNA in the other tissues. We detected strong correlations between peripheral blood mtDNA and tissue mtDNA content in early lactation. Peripheral blood forms an appropriate medium to display the cellular content of mtDNA copy numbers and consequently the cellular energy status of tissues during early lactation. PMID- 26686731 TI - Identification of a Lactobacillus plantarum strain that ameliorates chronic inflammation and metabolic disorders in obese and type 2 diabetic mice. AB - In this study, we identified a strain of lactic acid bacteria (LAB) that induces high levels of IL-10 production by immune cells, and evaluated the ability of the strain to suppress chronic inflammation and ameliorate metabolic disorders in in vitro and in vivo models. Among a collection of LAB strains, Lactobacillus plantarum strain OLL2712 (OLL2712) induced the highest levels of IL-10 production in mouse-derived dendritic cells and peritoneal macrophages. The anti inflammatory effects of this strain were evaluated using a co-culture system comprising RAW 264.7 and 3T3-L1 cells. We also administered heat-killed OLL2712 to obese and type 2 diabetic KKAy mice for 3 wk to evaluate the in vivo effects of the strain. The OLL2712 significantly decreased the production of proinflammatory cytokines in vitro. Likewise, the administration of OLL2712 significantly suppressed proinflammatory cytokine levels in both the visceral adipose tissue and the serum of KKAy mice, and reduced serum triglyceride concentrations. The strain also alleviated oxidative stress and adrenaline levels in the serum of KKAy mice. On the other hand, Lactobacillus gasseri strain MEP222804 (a moderate IL-10 inducer) did not ameliorate the systemic inflammation and hyperlipidemia in KKAy mice. Our results suggest that treatment with strong IL-10-inducing LAB has the potential to ameliorate metabolic disorders by suppressing chronic inflammation in the host animal. PMID- 26686733 TI - The Epistemology of Moral Bioenhancement. AB - Moral bioenhancement is the potential practice of manipulating individuals' moral behaviors by biological means in order to help resolve pressing moral issues such as climate change and terrorism. This practice has obvious ethical implications, and these implications have been and continue to be discussed in the bioethics literature. What have not been discussed are the epistemological implications of moral bioenhancement. This article details some of these implications of engaging in moral bioenhancement. The argument begins by making the distinction between moral bioenhancement that manipulates the contents of mental states (e.g. beliefs) and that which manipulates other, non-representational states (e.g. motivations). Either way, I argue, the enhanced moral psychology will fail to conform to epistemic norms, and the only way to resolve this failure and allow the moral bioenhancement to be effective in addressing the targeted moral issues is to make the moral bioenhancement covert. PMID- 26686732 TI - Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas. AB - This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of beta lactoglobulin and alpha-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from beta-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development. PMID- 26686734 TI - Distinct X chromosomal rearrangements in four haemophilia B patients with entire F9 deletion. AB - INTRODUCTION: Haemophilia B is an X-linked bleeding disorder caused by a coagulation factor IX gene (F9) abnormality. Numerous F9 defects have been identified to date; however, only a few with an entire F9 deletion have been reported in detail. AIM: To elucidate the cause of severe haemophilia B, we investigated the precise X chromosome abnormalities in four Japanese patients who did not show all amplifications in F9-specific PCR. METHODS: We analysed the patient's genomic DNA using Multiplex ligation-dependent probe amplification (MLPA). To assess the extent of any deletions, we further performed mapping PCRs, inverse PCRs or long-range PCRs and direct sequencing analyses of the X chromosome. RESULTS: We detected entire F9 deletions in four haemophilia B patients and identified the precise deleted regions of the X chromosome including F9. Patient 1 had a 149-kb deletion with breakpoints 90-kb upstream and 30-kb downstream from F9. Patients 2 and 3 showed 273-kb and 1.19-Mb deletions respectively. Patient 4 had two deleted regions: a 1663-bp deletion 1.34-Mb upstream from F9 and a 7.2-Mb deletion including F9. These distinct breakpoints found in four different patients suggest that the mechanism of X chromosome deletion may be different between individuals. Non-allelic homologous recombination (NAHR), microhomology-mediated break-induced replication (MMBIR) or fork stalling and template switching (FoSTeS) may occur in respective X chromosomes of the four haemophilia B patients analysed. CONCLUSIONS: We identified diverse X chromosomal rearrangements in four haemophilia B patients, which might be caused by distinct mechanisms of genomic rearrangement. PMID- 26686735 TI - Pyrene Scaffold as Real-Time Fluorescent Turn-on Chemosensor for Selective Detection of Trace-Level Al(III) and Its Aggregation-Induced Emission Enhancement. AB - A pyrene based fluorescent probe, 3-methoxy-2-((pyren-2yl-imino)methyl)phenol (HL), was synthesized via simple one-pot reaction from inexpensive reagents. It exhibited high sensitivity and selectivity toward Al(3+) over other relevant metal ions and also displayed novel aggregation-induced emission enhancement (AIEE) characteristics in its aggregate/solid state. When bound with Al(3+) in 1:1 mode, a significant fluorescence enhancement with a turn-on ratio of over ~200-fold was triggered via chelation-enhanced fluorescence through sensor complex (Al-L) formation, and amusingly excess addition of Al(3+), dramatic enhancement of fluorescence intensity over manifold through aggregate formation was observed. The 1:1 stoichiometry of the sensor complex (Al-L) was calculated from Job's plot based on UV-vis absorption titration. In addition, the binding site of sensor complex (Al-L) was well-established from the (1)H NMR titrations and also supported by the fluorescence reversibility by adding Al(3+) and EDTA sequentially. Intriguingly, the AIEE properties of HL may improve its impact and studied in CH3CN-H2O mixtures at high water content. To gain insight into the AIEE mechanism of the HL, the size and growth process of particles in different volume percentage of water and acetonitrile mixture were studied using time resolved photoluminescence, dynamic light scattering, optical microscope, and scanning electron microscope. The molecules of HL are aggregated into ordered one dimensional rod-shaped microcrystals that show obvious optical waveguide effect. PMID- 26686736 TI - Exclusive photorelease of signalling lipids at the plasma membrane. AB - Photoactivation of caged biomolecules has become a powerful approach to study cellular signalling events. Here we report a method for anchoring and uncaging biomolecules exclusively at the outer leaflet of the plasma membrane by employing a photocleavable, sulfonated coumarin derivative. The novel caging group allows quantifying the reaction progress and efficiency of uncaging reactions in a live cell microscopy setup, thereby greatly improving the control of uncaging experiments. We synthesized arachidonic acid derivatives bearing the new negatively charged or a neutral, membrane-permeant coumarin caging group to locally induce signalling either at the plasma membrane or on internal membranes in beta-cells and brain slices derived from C57B1/6 mice. Uncaging at the plasma membrane triggers a strong enhancement of calcium oscillations in beta-cells and a pronounced potentiation of synaptic transmission while uncaging inside cells blocks calcium oscillations in beta-cells and causes a more transient effect on neuronal transmission, respectively. The precise subcellular site of arachidonic acid release is therefore crucial for signalling outcome in two independent systems. PMID- 26686739 TI - Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient Centered Precision Medicine Approach. AB - Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG(r)) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG(r) and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG(r) and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use. PMID- 26686738 TI - CYP Genetic Variants, CYP Metabolite Levels, and Symptomatic Carotid Stenosis in Ischemic Stroke Patients. AB - AIM: To evaluate the relationship between CYP genetic polymorphisms and CYP metabolite levels with carotid artery stenosis in acute ischemic stroke (IS) patients. METHODS: Eleven single nucleotide polymorphisms (SNPs) of seven CYP genes were genotyped in 136 IS patients with carotid stenosis and 158 patients without carotid stenosis. CYP plasma metabolite levels [20 hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] were assessed in a subsample of 90 patients with carotid stenosis and 96 patients without carotid stenosis. We evaluated the relationship between assessed variants and carotid stenosis risk, variants with CYP metabolite levels, and variants in mediating the differences of CYP metabolite levels between patients with carotid stenosis and those without. Additionally, gene-gene interactions were analyzed to assess the interactive role of the assessed variants in affecting CYP metabolite levels and risk of carotid stenosis. RESULTS: The genotypes of rs17110453CC, rs751141GG, and rs9333025GG were significantly associated with carotid stenosis risk. Also these polymorphisms were associated with CYP plasma metabolite levels in patients with carotid stenosis. There was a significant gene-gene interaction between rs17110453 and rs9333025 in affecting the risk of carotid stenosis. Patients with rs17110453CC and rs9333025GG had a significantly higher risk of carotid stenosis than those with 17110453AA and rs9333025AA (OR=2.12, 95% CI: 1.13-7.26, P=0.013). CONCLUSIONS: Specific CYP450 gene SNPs and their interactions are associated with CYP450 plasma metabolite levels, which may partially explain their associations with carotid stenosis. Further studies are needed to validate our findings. PMID- 26686740 TI - HDL2/HDL3 Ratio Changes, Metabolic Syndrome Markers, and Other Factors in a Japanese Population. AB - AIM AND METHODS: The high-density lipoprotein 2 cholesterol (HDL2-C) to HDL3-C ratio is associated with insulin resistance, high-molecular-weight adiponectin (HMW-Ad), and metabolic syndrome (MetS) components and is useful for evaluating MetS in Japanese individuals. We investigated potential associations between changes in HDL2-C/HDL3-C and changes in MetS components, insulin resistance, adipocytokine, lipids, and lifestyle habits in 892 Japanese subjects who underwent annual health examinations twice at a mean interval of 1.1 years. Study subjects were divided into three groups on the basis of HDL2-C/HDL3-C changes. RESULTS: Average changes in waist circumference (WC) and HDL-C were significantly lower and higher, respectively, in the 0 to <0.5 and >=0.5 HDL2-C/HDL3-C change groups compared with those in the reference group (<0 HDL2-C/HDL3-C change). Among MetS components, average changes in HDL2-C/HDL3-C were associated with changes in WC and HDL-C. Average changes in HMW-Ad and the homeostasis model assessment of insulin resistance were significantly higher and lower, respectively, in the >=0.5 HDL2-C/HDL3-C change group compared with those in the reference group. In addition, the average low-density lipoprotein cholesterol (LDL-C) gradually decreased as HDL2-C/HDL3-C increased. The average change in LDL C was significantly lower in the 0 to <0.5 and >=0.5 HDL2-C/HDL3-C change groups than in the reference group. Moreover, a >=0.5 HDL2-C/HDL3-C change positively correlated with good lifestyle statuses in terms of smoking, physical activity, and alcohol consumption. CONCLUSION: Changes in HDL2-C/HDL3-C inversely correlated with changes in WC, insulin resistance, and LDL-C and positively correlated with HMW-Ad and good lifestyle habits. Therefore, HDL2-C/HDL3-C changes comprise a useful marker for both MetS and atherogenic conditions in Japanese population. PMID- 26686741 TI - Angiotensin-Converting Enzyme Inhibitor Prevents the Worsening of Renal Function in the Late Phase after Percutaneous Coronary Intervention. AB - AIM: The amount of contrast media and renal atheroemboli are risk factors for acute kidney injury after percutaneous coronary intervention (PCI). However, the chronic kidney injury after PCI has not been fully characterized. The purpose of this study was to investigate factors affecting renal function in the late phase after PCI by measuring serum Cystatin C (CysC). METHODS: In 143 consecutive patients who underwent elective PCI, CysC was evaluated at baseline and at 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association between %CysC and baseline characteristics, including medication use, was assessed. RESULTS: Of 143 patients, 86 had worsening renal function (WRF; %CysC >=0), and 57 did not (non-WRF; %CysC <0). Only the use of angiotensin converting enzyme inhibitor (ACEI) and baseline CysC were significantly different between WRF and non-WRF patients (15 vs. 40%, p=0.001 and 1.02+/-0.26 vs. 1.13+/ 0.26 mg/L, p=0.015). In univariate analysis, the use of ACEI and CysC were negatively associated with WRF [Odds ratio (OR)=0.26, 95% confidence interval (CI)=0.12-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.73, p=0.015]. Furthermore, multivariate analysis revealed that the use of ACEI and CysC significantly correlated with WRF (OR=0.26, 95% CI=0.11-0.57, p<0.001 and OR=0.20, 95% CI=0.05 0.74, p=0.016). The %CysC in 36 patients with ACEI was significantly lower than that in 107 patients without ACEI [median: -3.8%; interquartile range (IQR), 11.0 to 4.2%; vs. median: 3.3%; IQR -2.9 to 11.0%, p=0.001]. CONCLUSION: The use of ACEI was associated with lower CysC after PCI, suggesting that ACEI prevents worsening of renal function in late phase after PCI. PMID- 26686742 TI - Aging may Affect Insulin Action Independent of Adiposity in Non-Diabetic Subjects. PMID- 26686743 TI - Evaluation of Cardiovascular Risk Prediction for the Guidelines of Cardiovascular Diseases Prevention in Japan. PMID- 26686744 TI - The Novel Evidenced Assessment of Tortuosity system: interobserver reliability and agreement with clinical assessment. AB - PURPOSE: Computer-assisted assessment of vessel tortuosity is clinically useful in retinopathy of prematurity (ROP). However, poor image quality is often prohibitive for accurate segmentation by fully automated systems and semi automated systems are prone to unreliability. In the present work, we describe a method of retinal vessel tortuosity measurement by means of purpose-built image analysis software that does not require high image quality yet is also reliable. METHODS: Images were obtained from neonates at risk of ROP with Retcam Shuttle((r)) . Individual vessels were assessed with the semi-automated Novel Evidenced Assessment of Tortuosity (NEAT) system by two masked experimenters. Scores were compared to assess reliability. They were also compared against clinical scoring of individual vessels by two ROP screeners to assess relationship with clinical assessment. In a second image cohort, the mean of the most tortuous vessel in each of four quadrants in each eye (NEAT-O) was compared against the documented gold standard clinical grading of plus disease. RESULTS: Reliability of the NEAT system for 50 individual vessels using Bland-Altman plots was excellent. NEAT tortuosity scores for 50 individual vessels compared to clinical scoring showed strong correlation (0.706). Correlation between the NEAT O score for average tortuosity and gold standard for 167 eyes was modest (0.578). CONCLUSIONS: The NEAT system is intuitive, user-friendly and robust enough to be clinically useful in poor-quality images. It allows for a rapid, valid and reliable assessment of tortuosity of individual vessels and produces a tortuosity score that correlates well with severity of plus disease. PMID- 26686745 TI - [Lab-on-a-chip systems in the point-of-care diagnostics]. AB - The need in modern medicine for near-patient diagnostics being able to accelerate therapeutic decisions and possibly replacing laboratory measurements is significantly growing. Reliable and cost-effective bioanalytical measurement systems are required which - acting as a micro-laboratory - contain integrated biomolecular recognition, sensing, signal processing and complex microfluidic sample preparation modules. These micro- and nanofabricated Lab-on-a-chip systems open new perspectives in the diagnostic supply chain, since they are able even for quantitative, high-precision and immediate analysis of special disease specific molecular markers or their combinations from a single drop of sample. Accordingly, crucial requirements regarding the instruments and the analytical methods are the high selectivity, extremely low detection limit, short response time and integrability into the healthcare information networks. All these features can make the hierarchical examination chain shorten, and revolutionize laboratory diagnostics, evolving a brand new situation in therapeutic intervention. PMID- 26686746 TI - [Invasive neuromodulation in the treatment of drug-resistant epilepsies]. AB - Neuromodulation is one of the most developing new disciplines of medical science, which examines how electrical, chemical and mechanical interventions can modulate or change the functioning of the central and peripheral nervous system. Neuromodulation is a reversible form of therapy which uses electrical or mechanical stimulation or centrally-delivered drugs to modulate the abnormal function of the central nervous system in pain, spasticity, epilepsy, movement and psychiatric disorders, and certain cardiac, incontinency, visual and auditory diseases. Neuromodulation therapy has two major branches. Non-invasive neuromodulation includes transcranial magnetic simulation, direct current stimulation and transcutaneous electric nerve stimulation. Invasive neuromodulation includes deep brain stimulation, cortical stimulation, spinal cord stimulation, peripheral nerve stimulation, sacral nerve simulation, and subcutan stimulation. In this article the authors overview the apparently available neural interface technologies in epilepsy surgery. PMID- 26686737 TI - The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches. AB - Atherosclerosis is the leading cause of morbidity and mortality in the U.S., and is a multifactorial disease that preferentially occurs in regions of the arterial tree exposed to disturbed blood flow. The detailed mechanisms by which d-flow induces atherosclerosis involve changes in the expression of genes, epigenetic patterns, and metabolites of multiple vascular cells, especially endothelial cells. This review presents an overview of endothelial mechanobiology and its relation to the pathogenesis of atherosclerosis with special reference to the anatomy of the artery and the underlying fluid mechanics, followed by a discussion of a variety of experimental models to study the role of fluid mechanics and atherosclerosis. Various in vitro and in vivo models to study the role of flow in endothelial biology and pathobiology are discussed in this review. Furthermore, strategies used for the global profiling of the genome, transcriptome, miR-nome, DNA methylome, and metabolome, as they are important to define the biological and pathophysiological mechanisms of atherosclerosis. These "omics" approaches, especially those which derive data based on a single animal model, provide unprecedented opportunities to not only better understand the pathophysiology of atherosclerosis development in a holistic and integrative manner, but also to identify novel molecular and diagnostic targets. PMID- 26686747 TI - [Hybrid imaging: clinical evidence, opportunities]. AB - Nowadays the hybrid imaging technologies which combine the modern equipments of radiology and nuclear medicine play an important role in both the translational research process and clinical diagnostics. Among the routine diagnostic imaging procedures positron emission tomography and single photon emission computed tomography combined with computed tomography or magnetic resonance imaging currently belong to the most advanced techniques allowing that functional and morphological images can be superimposed on each other in the same position. The hybrid imaging equipments provide useful information about the pathological processes in the body due to their high sensibility and resolution. Furthermore, with the help of these imaging modalities we can get acquainted with the biochemical and pathobiochemical processes that are essential for understanding and treating diseases, or getting acquainted with the behaviour of a new drug candidate. With the help of the clinical and preclinical non-invasive in vivo molecular imaging systems the drug developing process can be shortened and its costs can be reduced. PMID- 26686748 TI - [Integrated optical sensor for rapid analysis of biological samples]. AB - INTRODUCTION: In the medical diagnostics of bacteria, the rapid detection of pathogenic microorganisms from body fluids is one of the most important tasks. The majority of the modern measuring techniques are based on specific labels bound to the bacteria. However, this strategy usually assumes a rather time consuming procedure involving several steps (e.g., the widely used enzyme-linked immunosorbent assay normally consists of 5 consecutive steps). Hence, there is an urgent need for the elaboration of rapid, "label-free" techniques, that are often based on Lab-on-a-chip devices. AIM: In this paper, the authors report on the development of a biosensor based on a miniature, integrated optical Mach-Zehnder interferometer. METHOD: Functionalization of the measuring arm of the sensor by antibodies, made the rapid and specific label-free detection of pathogens feasible. RESULTS: Using the combination of the interferometer with a microfluidic system, the device was able to detect Escherichia coli bacteria at concentrations as low as 10(6) colony forming unit/ml within minutes. CONCLUSIONS: This makes the newly developed biosensor a promising device for a wide range of applications, not only in medical microbiology, but microbial forensics, criminal investigations, bio-terrorism threats and in environmental studies as well. PMID- 26686749 TI - [Fast three-dimensional two-photon scanning methods for studying neuronal physiology on cellular and network level]. AB - INTRODUCTION: Two-photon microscopy is the ideal tool to study how signals are processed in the functional brain tissue. However, early raster scanning strategies were inadequate to record fast 3D events like action potentials. AIM: The aim of the authors was to record various neuronal activity patterns with high signal-to-noise ratio in an optical manner. METHOD: Authors developed new data acquisition methods and microscope hardware. RESULTS: Multiple Line Scanning enables the experimenter to select multiple regions of interests, doing this not just increases repetition speed, but also the signal-to-noise ratio of the fluorescence transients. On the same principle, an acousto-optical deflector based 3D scanning microscope has been developed with a sub-millisecond temporal resolution and a millimeter z-scanning range. Its usability is demonstrated by obtaining 3D optical recordings of action potential backpropagation in several hundred micrometers long neuronal processes of single neurons and by 3D random access scanning of Ca(2+) transients in hundreds of neurons in the mouse visual cortex. CONCLUSIONS: Region of interest scanning enables high signal-to-noise ratio and repetition speed, while keeping good depth penetration of the two photon microscopes. PMID- 26686751 TI - 3-D individual cell based computational modeling of tumor cell-macrophage paracrine signaling mediated by EGF and CSF-1 gradients. AB - High density of macrophages in mammary tumors has been associated with a higher risk of metastasis and thus increased mortality in women. The EGF/CSF-1 paracrine signaling increases the number of invasive tumor cells by both recruiting tumor cells further away and manipulating the macrophages' innate ability to open up a passage into blood vessels thus promoting intravasation and finally metastasis. A 3-D individual-cell-based model is introduced, to better understand the tumor cell-macrophage interactions, and to explore how changing parameters of the paracrine signaling system affects the number of invasive tumor cells. The simulation data and videos of the cell movements correlated well with findings from both in vitro and in vivo experimental results. The model demonstrated how paracrine signaling is necessary to achieve co-migration of tumor cells and macrophages towards a specific signaling source. We showed how the paracrine signaling enhances the number of both invasive tumor cells and macrophages. The simulations revealed that for the in vitro experiments the imposed no-flux boundary condition might be affecting the results, and that changing the setup might lead to different experimental findings. In our simulations, the 3 : 1 tumor cell/macrophage ratio, observed in vivo, was robust for many parameters but sensitive to EGF signal strength and fraction of macrophages in the tumor. The model can be used to identify new agents for targeted therapy and we suggest that a successful strategy to prevent or limit invasion of tumor cells would be to block the tumor cell-macrophage paracrine signaling. This can be achieved by either blocking the EGF or CSF-1 receptors or supressing the EGF or CSF-1 signal. PMID- 26686752 TI - Current and Future Perspectives on the Development, Evaluation, and Application of in Silico Approaches for Predicting Toxicity. AB - Exploiting non-testing approaches to predict toxicity early in the drug discovery development cycle is a helpful component in minimizing expensive drug failures due to toxicity being identified in late development or even during clinical trials. Changes in regulations in the industrial chemicals and cosmetics sectors in recent years have prompted a significant number of advances in the development, application, and assessment of non-testing approaches, such as (Q)SARs. Many efforts have also been undertaken to establish guiding principles for performing read-across within category and analogue approaches. This review offers a perspective, as taken from these sectors, of the current status of non testing approaches, their evolution in light of the advances in high-throughput approaches and constructs such as adverse outcome pathways, and their potential relevance for drug discovery. It also proposes a workflow for how non-testing approaches could be practically integrated within testing and assessment strategies. PMID- 26686753 TI - Molecular principle of the cyclin-dependent kinase selectivity of 4-(thiazol-5 yl)-2-(phenylamino) pyrimidine-5-carbonitrile derivatives revealed by molecular modeling studies. AB - Due to the high sequence identity of the binding pockets of cyclin-dependent kinases (CDKs), designing highly selective inhibitors towards a specific CDK member remains a big challenge. 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine derivatives are effective inhibitors of CDKs, among which the most promising inhibitor 12u demonstrates high binding affinity to CDK9 and attenuated binding affinity to other homologous kinases, such as CDK2. In this study, in order to rationalize the principle of the binding preference towards CDK9 over CDK2 and to explore crucial information that may aid the design of selective CDK9 inhibitors, MM/GBSA calculations based on conventional molecular dynamics (MD) simulations and enhanced sampling simulations (umbrella sampling and steered MD simulations) were carried out on two representative derivatives (12u and 4). The calculation results show that the binding specificity of 12u to CDK9 is primarily controlled by conformational change of the G-loop and variation of the van der Waals interactions. Furthermore, the enhanced sampling simulations revealed the different reaction coordinates and transient interactions of inhibitors 12u and 4 as they dissociate from the binding pockets of CDK9 and CDK2. The physical principles obtained from this study may facilitate the discovery and rational design of novel and specific inhibitors of CDK9. PMID- 26686754 TI - [Aneurysmal dissection of the middle cerebral artery]. PMID- 26686755 TI - Cetuximab activity in dysplastic lesions of the upper aerodigestive tract. AB - BACKGROUND: High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy. METHODS: We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk premalignancy. Patients were randomized to treatment with cetuximab 400mg/m(2) on week one followed by 250mg/m(2) on week 2-8 or observation, with the option for crossover to cetuximab therapy for patients originally randomized to the observation arm. RESULTS: Two of 19 enrolled patients did not complete therapy due to treatment toxicity. Analysis of 17 patients who completed the trial regimen show a trend toward a larger mean decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2) (P=0.082, one sided exact Wilcoxon rank sum test). However, in the observation group, none of the 5 patients (0%) achieved complete resolution of dysplasia; while 4 of 12 (33.3%) cetuximab treated patients had no remaining dysplasia after therapy. CONCLUSIONS: Treatment of high risk premalignancy of the upper aerodigestive tract with cetuximab alone may result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients. These results warrant further investigation in larger studies with increased statistical power. PMID- 26686756 TI - Condition-dependent physiological and behavioural responses to anthropogenic noise. AB - Anthropogenic (man-made) noise, a global pollutant of international concern, is known to affect the physiology and behaviour of a range of organisms. However, experimental studies have tended to focus on trait means; intra-population variation in responses are likely, but have rarely been explored. Here we use established experimental methods to demonstrate a condition-dependent effect of additional noise. We show that juvenile European eels (Anguilla anguilla) in good condition do not respond differently to playbacks of ambient coastal noise and coastal noise with passing ships. By contrast, the additional noise of ship passes caused an increase in ventilation rate and a decrease in startling to a looming predatory stimulus in poor condition eels. Intra-population variation in responses to noise has important implications both for population dynamics and the planning of mitigation measures. PMID- 26686757 TI - A quinoidal bis-phenalenyl-fused porphyrin with supramolecular organization and broad near-infrared absorption. AB - A bis-phenalenyl-fused porphyrin has been synthesized by thermal dehydro aromatization reaction regioselectively as a single syn-isomer. X-ray crystal structure revealed that both phenalenyl units of this porphyrin have close pi-pi contacts forming continuous network of interacting porphyrin rings. A broad and intense NIR absorption can be attributed to quinoidal character of bis-phenalenyl fused porphyrin. PMID- 26686758 TI - Responses of community-level plant-insect interactions to climate warming in a meadow steppe. AB - Climate warming may disrupt trophic interactions, consequently influencing ecosystem functioning. Most studies have concentrated on the temperature-effects on plant-insect interactions at individual and population levels, with a particular emphasis on changes in phenology and distribution. Nevertheless, the available evidence from the community level is limited. A 3-year field manipulative experiment was performed to test potential responses of plant and insect communities, and plant-insect interactions, to elevated temperature in a meadow steppe. Warming increased the biomass of plant community and forbs, and decreased grass biomass, indicating a shift from grass-dominant to grass-forb mixed plant community. Reduced abundance of the insect community under warming, particularly the herbivorous insects, was attributed to lower abundance of Euchorthippus unicolor and a Cicadellidae species resulting from lower food availability and higher defensive herbivory. Lower herbivore abundance caused lower predator species richness because of reduced prey resources and contributed to an overall decrease in insect species richness. Interestingly, warming enhanced the positive relationship between insect and plant species richness, implying that the strength of the plant-insect interactions was altered by warming. Our results suggest that alterations to plant-insect interactions at a community level under climate warming in grasslands may be more important and complex than previously thought. PMID- 26686759 TI - Open reduction internal fixation has fewer short-term complications than shoulder arthroplasty for proximal humeral fractures. AB - BACKGROUND: Open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and anatomic or reverse total shoulder arthroplasty (TSA/RTSA) are surgical treatment options for proximal humeral fractures (PHFx). Little is known about comparative complication rates. We aimed to determine whether ORIF for PHFx has fewer 30-day complications than HA and TSA/RTSA and to define independent risk factors for 30-day complications. METHODS: Patients who underwent ORIF, HA, or TSA/RTSA for PHFx between 2006 and 2013 were identified from the National Surgical Quality Improvement Program database. Potential patient and surgical risk factors and 30-day postoperative complications were extracted. Univariate and multivariate analyses were conducted. RESULTS: We identified 1791 patients (1262 ORIF, 404 HA, and 125 TSA/RTSA). The overall complication rate was 13.0% in ORIF, 22.0% in HA, and 23.2% in TSA/RTSA (P < .001), driven primarily by rates of blood transfusion. Multivariate analyses demonstrated ORIF was an independent protective factor against minor complications (P = .009) and overall complications (P = .028) but not against major complications (P = .351). Risk factors for overall complications included preoperative sepsis (P < .001), higher American Society of Anesthesiologists Physical Status Classification (P < .001), dependent functional status (P = .002), transfusion of at least 5 units in the 72 hours before surgery (P = .002), longer operative time (P = .003), and a history of chronic obstructive pulmonary disease (P = .028). CONCLUSIONS: After adjusting for patient factors, ORIF for PHFx remains an independent protective factor against overall complications and minor complications compared with HA and TSA/RTSA, primarily due to lower rates of blood transfusion. Patient comorbidities play a larger role than the procedure selected in predicting short term complications. PMID- 26686760 TI - Early postoperative repair status after rotator cuff repair cannot be accurately classified using questionnaires of patient function and isokinetic strength evaluation. AB - BACKGROUND: This study investigated if patients with an intact tendon repair or partial-thickness retear early after rotator cuff repair display differences in clinical evaluations and whether early tendon healing can be predicted using these assessments. METHODS: We prospectively evaluated 60 patients at 16 weeks after arthroscopic supraspinatus repair. Evaluation included the Oxford Shoulder Score, 11-item version of the Disabilities of the Arm, Shoulder and Hand, visual analog scale for pain, 12-item Short Form Health Survey, isokinetic strength, and magnetic resonance imaging (MRI). Independent t tests investigated clinical differences in patients based on the Sugaya MRI rotator cuff classification system (grades 1, 2, or 3). Discriminant analysis determined whether intact repairs (Sugaya grade 1) and partial-thickness retears (Sugaya grades 2 and 3) could be predicted. RESULTS: No differences (P < .05) existed in the clinical or strength measures. Although discriminant analysis revealed the 11-item version of the Disabilities of the Arm, Shoulder and Hand produced a 97% true-positive rate for predicting partial thickness retears, it also produced a 90% false-positive rate whereby it incorrectly predicted a retear in 90% of patients whose repair was intact. The ability to discriminate between groups was enhanced with up to 5 variables entered; however, only 87% of the partial-retear group and 36% of the intact-repair group were correctly classified. CONCLUSIONS: No differences in clinical scores existed between patients stratified by the Sugaya MRI classification system at 16 weeks. An intact repair or partial-thickness retear could not be accurately predicted. Our results suggest that correct classification of healing in the early postoperative stages should involve imaging. PMID- 26686761 TI - Quantum transport through a Coulomb blockaded quantum emitter coupled to a plasmonic dimer. AB - We study the electron transmission through a Coulomb blockaded quantum emitter coupled to metal nanoparticles possessing plasmon resonances by employing the time-dependent non-crossing approximation. We find that the coupling of the nanoparticle plasmons with the excitons results in a significant enhancement of the conductance through the discrete state with higher energy beyond the unitarity limit while the other discrete state with lower energy remains Coulomb blockaded. We show that boosting the plasmon-exciton coupling well below the Kondo temperature increases the enhancement adding another quantum of counductance upon saturation. Finite bias and increasing emitter resonance energy tend to reduce this enhancement. We attribute these observations to the opening of an additional transport channel via the plasmon-exciton coupling. PMID- 26686762 TI - Resilience Is Complicated, but Comparable: A Reply to Yeung and Richardson. PMID- 26686763 TI - Identification of epitopes on HLA-DRB alleles reacting with antibodies in sera from women sensitized during pregnancy. AB - This report describes a HLAMatchmaker-based antibody analysis of post-pregnancy sera with antibodies against child-specific HLA-DR epitopes. These sera were reactive in IgG-binding assays with single allele bead (SAB) panels on a Luminex platform. The antibody specificity analysis focused on DRB epitopes that have been recorded in the International HLA Epitope Registry (http://www.epregistry.com.br) as experimentally verified with informative antibodies but we also considered other eplets that predict potential epitopes. The SAB panel has in several instances two or more alleles corresponding to the same serologically defined DR antigen and we selected six sera were with different reactivity patterns with DR1, DR4, DR13 and/or DR52 alleles. We demonstrate here how amino acid differences between these alleles can provide useful information in the determination of new epitope specificities of antibodies in these sera. Eight newly antibody-verified epitopes were identified including three that correspond to eplets paired with self-residue configurations. Epitope specificity information appears to be useful in the prediction of mismatch acceptability of non-SAB alleles within serological DR antigen groups. PMID- 26686764 TI - Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass. AB - Because of the reduced potential for osteogenesis in aging bone marrow stromal cells, the balance of bone metabolism becomes disrupted, leading to various bone diseases. An increase in reactive oxygen species has been determined to be one of the key factors that accelerates the aging process in BMSCs. In these cells, increased expression of NADPH oxidases is the major source of ROS. In the current study, we suppressed the expression of NOX using apocynin, an effective antioxidant and free radical scavenger, and the results showed that aging BMSCs exhibited an enhanced potential for osteogenesis. The expression of potential key targets influencing this reversal was evaluated using qRT-PCR, and the expression of p53 was shown to be reduced with the suppression of NOX. We speculate that this may be one of the major reasons for the reversal of the aging process. We also examined the effect of apocynin in vivo, and the results showed that in SAMP6 mice, bone mineral density and total bone volume were increased after 3 months of apocynin treatment. In conclusion, our results demonstrate that in aging BMSCs, suppression of NADPH oxidase by apocynin partially reverses the aging process and enhances osteogenic potential. PMID- 26686766 TI - The relationship between female genital cutting and sexual problems experienced in the first two months of marriage. AB - OBJECTIVE: To examine the relationship between female genital cutting (FGC) and sexual problems experienced by couples in the first 2 months of marriage ("honeymoon distress"). METHODS: A multicenter cross-sectional study was conducted at centers in Assiut and Sohag, Egypt, between March 1, 2011, and March 31, 2014. Eligible couples presented with sexual problems during the first 2 months of marriage. Couples were interviewed and asked to complete a pre-designed questionnaire, and a genital examination was performed. The primary outcomes of the study were the contribution of FGC to honeymoon distress and the effect of FGC on quality of life. RESULTS: Overall, 430 couples enrolled in the study. FGC was present in 376 (87.4%) women. The main presenting feature of honeymoon distress was superficial dyspareunia, which affected 291 (77.4%) women with FGC versus 16 (29.6%) of 54 without FGC (hazard ratio 8.13, 95% confidence interval 4.32-15.30). Women with FGC were more likely to have a poor quality of life during the first 2 months of marriage than were those without FGC (279 [74.2%] vs 13 [24.1%]; odds ratio 9.07, 95% confidence interval 4.66-17.64). CONCLUSION: FGC was found to be a contributing factor to honeymoon distress. PMID- 26686765 TI - Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders. AB - Clustered regularly interspaced short palindromic repeat (CRISPR) has arisen as a frontrunner for efficient genome engineering. However, the potentially broad therapeutic implications are largely unexplored. Here, to investigate the therapeutic potential of CRISPR/Cas9 in a diverse set of genetic disorders, we establish a pipeline that uses readily obtainable cells from affected individuals. We show that an adapted version of CRISPR/Cas9 increases the amount of utrophin, a known disease modifier in Duchenne muscular dystrophy (DMD). Furthermore, we demonstrate preferential elimination of the dominant-negative FGFR3 c.1138G>A allele in fibroblasts of an individual affected by achondroplasia. Using a previously undescribed approach involving single guide RNA, we successfully removed large genome rearrangement in primary cells of an individual with an X chromosome duplication including MECP2. Moreover, removal of a duplication of DMD exons 18-30 in myotubes of an individual affected by DMD produced full-length dystrophin. Our findings establish the far-reaching therapeutic utility of CRISPR/Cas9, which can be tailored to target numerous inherited disorders. PMID- 26686767 TI - Involvement of TLR4 in the long-term epigenetic changes, rewarding and anxiety effects induced by intermittent ethanol treatment in adolescence. AB - Studies in humans and experimental animals have demonstrated the vulnerability of the adolescent brain to actions of ethanol and the long-term consequences of binge drinking, including the behavioral and cognitive deficits that result from alcohol neurotoxicity, and increased risk to alcohol abuse and dependence. Although the mechanisms that participate in these effects are largely unknown, we have shown that ethanol by activating innate immune receptors, toll-like receptor 4 (TLR4), induces neuroinflammation, impairs myelin proteins and causes cognitive dysfunctions in adolescent mice. Since neuroimmune signaling is also involved in alcohol abuse, the aim of this study was to assess whether ethanol treatment in adolescence promotes the long-term synaptic and molecular events associated with alcohol abuse and addiction. Using wild-type (WT) and TLR4-deficient (TLR4-KO) adolescent mice treated intermittently with ethanol (3g/kg) for 2 weeks, we showed that binge-like ethanol treatment in adolescent mice promotes short- and long-term alterations in synaptic plasticity and epigenetic changes in the promoter region of bdnf and fosb, which increased their expression in the mPFC of young adult animals. These molecular events were associated with long-term rewarding and anxiogenic-related behavioral effects, along with increased alcohol preference. Our results further showed the participation of neuroimmune system activation and the TLR4 signaling response since deficient mice in TLR4 (TLR4-KO) are protected against molecular and behavioral alterations of ethanol in the adolescent brain. Our results highlight a new role of the neuroimmune function and open up new avenues to develop pharmacological treatments that can normalize the immune signaling responsible for long-term effects in adolescence, including alcohol abuse and related disorders. PMID- 26686768 TI - Lower extremity power in female soccer athletes: a pre-season and in-season comparison. AB - PURPOSE: Lower extremity power is an important physical capacity of a soccer athlete. Power represents, and can be modified by, the training of strength and speed. Pre-season and in-season training differs in the relative emphasis on these two quantities. It is nevertheless desirable that the mechanical power remain the same or become higher during the in-season period. The purpose of this study was to identify changes in quantities related to "explosive strength" and to check whether, in collegiate female soccer players, pre- and inseason lower extremity power will remain unaltered. METHODS: Twenty collegiate female soccer players, representing all field positions, participated. Lower extremity power was assessed by a series of drop jumps executed from four different heights (15, 30, 45, and 60 cm). Mechanical power was calculated using subject's mass, jump height, and acceleration due to gravity. This value was further normalized by body mass of each athlete to obtain the relative (or normalized) mechanical power. RESULTS: The normalized lower extremity mechanical power was highest when landing from the 30 cm height for both pre- and inseason periods. However, contrary to expectations, it turned out lower during the in-season than during the pre-season test, even though no significant differences were found between the corresponding jump heights. CONCLUSIONS: It is concluded that altered, perhaps inadequate, training strategies were employed during the in-season period. Besides, advantages of adding the relative mechanical power as a season readiness indicator are underlined compared with relying on the jump height alone. PMID- 26686769 TI - Integrative drug efficacy assessment of Danggui and European Danggui using NMR based metabolomics. AB - Danggui (DG) is a commonly used herbal drug in traditional Chinese medicine, and usually adulterated with European Danggui (EDG) due to the increasing demand. In present study, global metabolic profiling with NMR coupled with integrative drug efficacy evaluation methods was performed to compare and discover underlying blood-enriching regulation mechanisms of DG and EDG on blood deficiency rats induced by acetyl phenylhydrazine (APH). Totally, the contents of 12 key metabolites in serum and 4 in urine of DG group, 7 in serum and 4 in urine of EDG group were significantly reversed in comparison with model group. DG was more effective than EDG as revealed by the relative distance, efficacy index and similarity analysis. The metabolism pathways analysis showed that the better effect of DG maybe related with the regulatory effect on valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, as well as nicotinate and nicotinamide metabolism. The results presented here showed that metabolomic coupled with efficacy index and similarity analysis made it possible to disclose the subtle biological difference between DG and EDG, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs. PMID- 26686770 TI - Peripheral blood T- and B-cell immunophenotypic abnormalities in selected women with unexplained recurrent miscarriage. AB - We aimed to investigate if women with recurrent miscarriage disclosed abnormalities in the maturation and activation status of peripheral blood lymphocyte subsets. In a case control study, 24 women with recurrent miscarriage, 37 women with children but no history of miscarriage and 39 women without previous pregnancies were evaluated. Lymphocyte subsets were evaluated using three-colour flow-cytometry. Selected women with recurrent miscarriage had significantly higher absolute counts of central memory CD4+ T-cells, CD8+DR+ T cells and memory non-switched B-cells than the control groups. Recurrent miscarriage may be associated with abnormalities of the maturation and activation status of peripheral blood T and B lymphocytes. PMID- 26686771 TI - Bridging external fixation versus non-bridging external fixation for unstable distal radius fractures: A systematic review and meta-analysis. AB - OBJECTIVE: A systematic review and meta-analysis was conducted to compare the relative effectiveness of bridging external fixation and non-bridging external fixation for distal radius fractures treatment. METHOD: Relevant literature were comprehensively searched using the PubMed, Springer Link, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases without any language restrictions. STATA Version 12.0 software and Comprehensive Meta-analysis 2.0 were applied. RESULTS: A total of 905 patients with distal radius fracture from six eligible cohort studies were selected for statistical analysis. Our meta-analysis results indicate that the non-bridging cases had a higher risk of pin track infection, rupture of the extensor pollicis longus and nerve injury than the bridging cases. Subgroup analysis stratified by country indicated non-bridging patients showed evidence of an increased risk of pin track infection and higher risk of rupture of the extensor pollicis longus compared with the patients treated with bridging external fixation in the UK population. The follow-up results showed flexion degree of patients treated with non-bridging external fixation was slightly better than that of patients treated with bridging external fixation (P < 0.05). CONCLUSION: There is evidence in our systematic review and meta-analysis to support that bridging external fixation can reduce the incidence of pin tract infections and nerve injury compared to non-bridging external fixation, but have no significant difference in other complications and the recovery of wrist joint function. Bridging external fixation could therefore be a better choice in patients with distal radius fractures. PMID- 26686772 TI - Modified technique of transoral release in one-stage anterior release and posterior reduction for irreducible atlantoaxial dislocation. AB - BACKGROUND: One-stage anterior release and posterior reduction is one of the most effective methods for irreducible atlantoaxial dislocation. However, the criteria of appropriate tissue release for successful posterior reduction is yet to be confirmed. Hence, an assistant technique using the transoral approach to verify satisfactory release is required. To evaluate the efficacy of the modified technique of transoral release for irreducible atlantoaxial dislocation (IAAD) with patients underwent one-stage anterior release and posterior reduction. METHODS: Between January 2009 and June 2014, 23 consecutive patients diagnosed with IAAD free from bony union between the C1-C2 facet joints on reconstructive computed tomography scan underwent one-stage anterior release and posterior reduction after no response to 2 weeks of skull traction. During transoral release, an elevator was used as a lever repeatedly to confirm a 3-5 mm bilateral joint space between the lateral masses of the atlas and axis. The release was accomplished since a 3-5 mm joint space was achieved. After anterior release, posterior reduction and instrumented fusion were subsequently performed. RESULTS: All patients were observed for an average of 18 (range 6-50) months. Nineteen of 23 patients achieved complete reduction while four had an incomplete reduction. Significant differences in pre- and postoperative JOA scores and cervicomedullary angle (CMA) were found. Twenty-one patients presenting with myelopathy had a JOA score of 12.9 at final follow-up, improved from 7.8 before surgery. The mean CMA improved to 143.5 degrees postoperatively from 101.8 degrees preoperatively. Bony fusion was confirmed in all cases under radiologic assessment during follow up; there were no instrument failures. CONCLUSION: The modified technique of transoral release provides appropriate criteria for anterior release, to achieve good posterior reduction without excessive tissue release or intraspinal manipulation, proving its value as an assistant technique in one-stage anterior release and posterior reduction for IAAD. PMID- 26686773 TI - Spiroepoxytriazoles Are Fumagillin-like Irreversible Inhibitors of MetAP2 with Potent Cellular Activity. AB - Methionine aminopeptidases (MetAPs) are responsible for the cotranslational cleavage of initiator methionines from nascent proteins. The MetAP2 subtype is up regulated in many cancers, and selective inhibition of MetAP2 suppresses both vascularization and growth of tumors in animal models. The natural product fumagillin is a selective and potent irreversible inhibitor of MetAP2, and semisynthetic derivatives of fumagillin have shown promise in clinical studies for the treatment of cancer, and, more recently, for obesity. Further development of fumagillin derivatives has been complicated, however, by their generally poor pharmacokinetics. In an attempt to overcome these limitations, we developed an easily diversifiable synthesis of a novel class of MetAP2 inhibitors that were designed to mimic fumagillin's molecular scaffold but have improved pharmacological profiles. These substances were found to be potent and selective inhibitors of MetAP2, as demonstrated in biochemical enzymatic assays against three MetAP isoforms. Inhibitors with the same relative and absolute stereoconfiguration as fumagillin displayed significantly higher activity than their diastereomeric and enantiomeric isomers. X-ray crystallographic analysis revealed that the inhibitors covalently modify His231 in the MetAP2 active site via ring-opening of a spiroepoxide. Biochemically active substances inhibited the growth of endothelial cells and a MetAP2-sensitive cancer cell line, while closely related inactive isomers had little effect on the proliferation of either cell type. These effects correlated with altered N-terminal processing of the protein 14-3-3-gamma. Finally, selected substances were found to have improved stabilities in mouse plasma and microsomes relative to the clinically investigated fumagillin derivative beloranib. PMID- 26686775 TI - Increased levels of CSF CD59 in neuromyelitis optica and multiple sclerosis. AB - BACKGROUND: Complement activation is important in multiple sclerosis (MS) and is essential for anti-aquaporin 4 antibodies to damage the central nervous system in neuromyelitis optica (NMO). Little is known about the role of cerebrospinal fluid (CSF) regulators of complement activation in NMO and MS. We determined whether CSF CD59, which is a complement regulator and C5b-9 formation inhibitor, is involved in the pathogenesis of NMO and MS. METHODS: We analyzed CSF levels of CD59 in 30 patients with NMO, 22 patients with MS, and 24 patients with non inflammatory neurological disorders (NINDs). Possible correlations between CSF CD59 levels and the clinical and laboratory variables in patients with NMO and MS were also reviewed. RESULTS: CSF CD59 levels in patients with NMO and MS were higher than those in patients with NINDs (p<0.001), and those in patients with NMO decreased after treatment. No significant correlations were found between CSF CD59 levels and clinical and laboratory parameters in NMO and MS. CONCLUSION: High CSF CD59 levels in NMO and MS may reflect inflammation, damage, and/or complement activation in the central nervous system. PMID- 26686776 TI - Phenotypic variability in a Tunisian family with X-linked adrenoleukodystrophy caused by the p.Gln316Pro novel mutation. AB - INTRODUCTION: X-linked adrenoleukodystrophy is a neurodegenerative recessive disorder that affects the brain white matter and associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of the Very Long Chain Fatty Acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding cassette transporter located in the peroxisomal membrane protein. PATIENTS AND METHODS: The present study reports the clinical, biochemical and molecular investigation in a Tunisian family with two affected males with childhood cerebral adrenoleukodystrophy. RESULTS: The ABCD1 gene sequencing indicated a novel hemizygous missense mutation c.947A>C (p.Gln316Pro) in the exon 2 of the ABCD1 gene in the patients, their mother and their sisters. This missense variation was predicted to be possibly damaging by the PolyPhen and SIFT prediction software. Although presence of the same mutation c.947A>C in both siblings, they present different clinical signs. CONCLUSIONS: Based on the disease's progress, the clinical signs and biochemical aspects between the two siblings, we demonstrate that there is no correlation genotype-phenotype. PMID- 26686774 TI - Immunosurveillance and immunotherapy of tumors by innate immune cells. AB - Increasing evidence supports a role for innate immune effector cells in tumor surveillance. Natural killer (NK) cells and myeloid cells represent the two main subsets of innate immune cells possessing efficient but quite different tumor suppressive abilities. Here, we describe the germline-encoded NK cell receptors that play a role in suppressing tumor development and describe briefly the cellular pathways leading to the upregulation of their ligands in tumor cells. We also describe mechanisms underlying the elimination of tumor cells by macrophages and a recently characterized mechanism dedicated to sensing cytosolic DNA that is implicated in antitumor immune responses. PMID- 26686777 TI - HIQA's CEA of Breast Screening: Pragmatic Policy Recommendations are Welcome, but ACERs Reported as ICERs are Not. AB - The Health Information and Quality Authority (HIQA) is Ireland's statutory cost effectiveness analysis (CEA) agency. It recently published a CEA of screening strategies for women at elevated risk of breast cancer. Although the strategies recommended by HIQA exceed Ireland's cost-effectiveness threshold, they can reasonably be welcomed as a pragmatic response to constraints on disinvestment and are expected to improve screening cost-effectiveness. What is not welcome, however, is HIQA's reporting of average cost-effectiveness ratios (ACERs) as incremental cost-effectiveness ratios (ICERs). The distinction between ACERs and ICERs is well understood in CEA, as is the fact that ICERs not ACERs are the appropriate metric to determine cost-effectiveness. This article critiques HIQA's reporting, considering the implications for the particular case of breast cancer screening and the broader context of consistency of and confidence in CEA as a guide to resource allocation in Ireland. The reporting of ACERs as ICERs is unlikely to be of any great significance in the particular case of screening women at elevated risk of breast cancer, given likely constraints on disinvestment. Despite this, ICERs still need to be reported correctly. If thresholds are exceeded in certain cases, then it is important that decision makers appreciate by how much. More generally, using ACERs in some cases and ICERs in others raises concerns that methods are being applied inconsistently, which risks compromising confidence in CEA in Ireland. As Ireland's statutory CEA authority, HIQA has a special onus of responsibility to ensure established methods are applied correctly. PMID- 26686778 TI - Impact and Cost-Effectiveness of Hypothetical Strategies to Enhance Retention in Care within HIV Treatment Programs in East Africa. AB - OBJECTIVES: Attrition from care among HIV infected patients can lead to poor clinical outcomes. Our objective was to evaluate hypothetical interventions seeking to improve retention-in-care (RIC) for HIV-infected patients in East Africa, asking whether they could offer favorable value compared to earlier ART initiation. METHODS: We used a micro-simulation model to analyze two RIC focused strategies within an East African HIV treatment program--"risk reduction," defined as intervention(s) that decrease the risk of attrition from care; and "outreach," defined as interventions that find patients and relink them with care. We compared this to earlier ART treatment as a measure of the potential health benefits forgone (e.g., opportunity cost). RESULTS: Reducing attrition by 40% at an average cost of $10 per person remains a less efficient use of resources compared to ensuring full access to ART (cost- effectiveness ratio $1300 vs $3700) for ART eligible patients. An outreach intervention had limited clinical benefit in our simulation. If intervention costs are <$10 per person, however, an intervention able to achieve a 40% (or greater) reduction in attrition may be a cost-effective next implementation option following implementation of earlier ART treatment. CONCLUSIONS: Our results suggest that programs should consider retention focused programs once they have already achieved high degrees of ART coverage among eligible patients. It is important that decision makers understand the epidemiology and associated outcomes of those patients who are classified as lost to follow up in their systems prior to implementation in order to achieve the highest value. PMID- 26686779 TI - Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study. AB - BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of ?1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of ?11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context. PMID- 26686780 TI - The Burden of Diabetes Mellitus in Patients with Coronary Heart Disease: A Methodological Approach to Assess Quality-Adjusted Life-Years Based on Individual Level Longitudinal Survey Data. AB - BACKGROUND: Reliable burden of disease (BOD) estimates are needed to support decision making in health care. OBJECTIVES: The objective of this study was to introduce an analysis approach based on individual-level longitudinal survey data that estimates the burden of diabetes in patients with coronary heart disease in terms of quality-adjusted life-years (QALYs) lost. METHODS: Data from two postal surveys (2006, N = 1022; 2010-2011, N = 716) of survivors from the KORA Myocardial Infarction Registry in Southern Germany were analyzed. Accumulated QALYs were calculated for each participant over a mean observation time of 4.1 years, considering the noninformative censoring structure of the follow-up study. Linear regression models were used to estimate the loss in (quality-unadjusted) life-years and QALYs between patients with and without diabetes, and generalized additive models were used to analyze the nonlinear association with age. The cross-sectional and longitudinal association with quality of life (QOL) and QOL change and the impact on mortality were analyzed to enhance the understanding of the observed results. RESULTS: Diabetes was associated with a reduced QOL at baseline (cross-sectional: beta = -0.069; P < 0.001), but not with a significant longitudinal QOL change. Mortality in patients with diabetes was increased (hazard ratio = 1.68; P < 0.005). This resulted in a loss of 0.14 life-years (P = 0.003) and 0.37 QALYs (P < 0.001). Results from generalized additive models indicated that the burden of diabetes is less pronounced in older subjects. CONCLUSIONS: The application of the proposed approach provides confounder adjusted BOD estimates for the studied time horizon and can be used to compare the BOD across different chronic conditions. Curative efforts are needed to diminish the substantial diabetes-related QALY gap. PMID- 26686781 TI - Cost-Effectiveness of Disease Management Programs for Cardiovascular Risk and COPD in The Netherlands. AB - BACKGROUND: Disease management programs (DMPs) for cardiovascular risk (CVR) and chronic obstructive pulmonary disease (COPD) are increasingly implemented in The Netherlands to improve care and patient's health behavior. OBJECTIVE: The aim of this study was to provide evidence about the (cost-) effectiveness of Dutch DMPs as implemented in daily practice. METHODS: We compared the physical activity, smoking status, quality-adjusted life-years, and yearly costs per patient between the most and the least comprehensive DMPs in four disease categories: primary CVR prevention, secondary CVR prevention, both types of CVR prevention, and COPD (N = 1034). Propensity score matching increased comparability between DMPs. A 2-year cost-utility analysis was performed from the health care and societal perspectives. Sensitivity analysis was performed to estimate the impact of DMP development and implementation costs on cost-effectiveness. RESULTS: Patients in the most comprehensive DMPs increased their physical activity more (except for primary CVR prevention) and had higher smoking cessation rates. The incremental QALYs ranged from -0.032 to 0.038 across all diseases. From a societal perspective, the most comprehensive DMPs decreased costs in primary CVR prevention (certainty 57%), secondary CVR prevention (certainty 88%), and both types of CVR prevention (certainty 98%). Moreover, the implementation of comprehensive DMPs led to QALY gains in secondary CVR prevention (certainty 92%) and COPD (certainty 69%). CONCLUSIONS: The most comprehensive DMPs for CVR and COPD have the potential to be cost saving, effective, or cost-effective compared with the least comprehensive DMPs. The challenge for Dutch stakeholders is to find the optimal mixture of interventions that is most suited for each target group. PMID- 26686782 TI - The Suitability of End Point Designs for Health Technology Assessment in Chronic Pain Studies. AB - OBJECTIVES: To identify the pain instruments and study end points most commonly used in clinical trial settings and to provide insight into the extent to which outcome measures in clinical studies are meeting payer needs. METHODS: A literature review was conducted to identify published clinical studies and ongoing/recently completed registered trials in chronic pain. Inclusion criteria were interventional study, chronic pain in adults, and pain measured within the primary end point. RESULTS: Of 1256 PubMed citations and 3006 clinical trial registry entries, 356 reported large clinical studies in pain populations (e.g., malignant, neuropathic, functional, and musculoskeletal). Studies were designed for superiority in 28% of PubMed citations and 8% of registry entries. The primary end points of most studies were single-dimension pain instruments, such as the numerical rating scale (n = 131) and the visual analogue scale (n = 69). In cases in which multidimensional pain end points were used, this was most commonly the Brief Pain Inventory (n = 37). Payer-relevant end points were typically limited to secondary end points, and were limited and/or reported inconsistently in published studies and ongoing/recently completed studies: preference-weighted quality of life (36% and 42%), resource use (2% and 8%), physical function (28% and 39%), and psychological function (25% and 24%). CONCLUSIONS: Most pain trials were not designed to show superiority to an active comparator, and they used single-dimension pain scales as their primary end point in combination with a broader selection of secondary end points. The inclusion of payer-relevant end points among clinical trials was inconsistent. PMID- 26686783 TI - Development of the Treatment Inventory of Costs in Psychiatric Patients: TIC-P Mini and Midi. AB - BACKGROUND: Medical costs of (psychiatric) illness can be validly measured with patient report questionnaires. These questionnaires comprise many detailed items resulting in lengthy administrations. OBJECTIVES: We set out to find the minimal number of items needed to retrieve 80% and 90% of the costs as measured by the Treatment Inventory of Costs in Patients with psychiatric disorders (TIC-P). METHODS: The TIC-P is a validated patient-reported outcome measure concerning the utilization of medical care and productivity losses. The present study focused on direct medical costs. We applied data of 7756 TIC-P administrations from three studies in patients with mental health care issues. Items that contribute least to the total cost were eliminated, providing that 80% and 90% of the total cost was retained. RESULTS: Average medical costs per patient were ?658 over the last 4 weeks. The distribution of cost was highly skewed, and 5 of the 14 items of the TIC-P accounted for less than 10% of the total costs. The 80% Mini version of the TIC-P required five items: ambulatory services, private practice, day care, general hospital, and psychiatric clinic. The TIC-P Midi 90% inventory required eight items. Both had variance between the three samples in the optimal choice of the items. CONCLUSIONS: The number of items of the TIC-P can be reduced considerably while maintaining 80% and 90% of the medical costs estimated by the complete TIC-P. The reduced length makes the questionnaire more suitable for routine outcome monitoring. PMID- 26686784 TI - Development and Content Validity Testing of a Patient-Reported Treatment Acceptance Measure for Use in Patients Receiving Treatment via Subcutaneous Injection. AB - BACKGROUND: New therapies in development for lowering low-density lipoprotein cholesterol, such as alirocumab, require administration by subcutaneous injections. There is a need to assess the acceptance of such treatments and their mode of administration. OBJECTIVES: To develop a novel patient-reported outcome measure, the Injection-Treatment Acceptance Questionnaire (I-TAQ), and assess its content validity using qualitative methods. METHODS: Concepts generated from a literature and instrument review informed the initial drafting of 17 items in the I-TAQ, with item wording adapted from three existing instruments. Three rounds of qualitative interviews were conducted with 29 US-English speaking patients at high cardiovascular risk. Concept elicitation questioning was used to explore patients' treatment experiences followed by cognitive debriefing of the I-TAQ using "think-aloud" methods. Verbatim transcripts were analyzed using thematic analysis. RESULTS: Qualitative analysis of concept elicitation data identified the following relevant concepts: perceived efficacy, side effects, self-efficacy, convenience, and overall acceptance. Seven (24%) patients discussed an initial fear of needles, but described this as subsiding with no impact on adherence. Five items were added after round one interviews, three of which were retained after round two testing in which two further items were added, forming the conceptually comprehensive 22-item I-TAQ. Patients demonstrated good understanding of item wording, instructions, response scales, and recall period. CONCLUSIONS: Successive rounds of in-depth interviews resulted in a treatment acceptance measure with strong content validity. Pending demonstration of its psychometric properties, the I-TAQ may prove to be a valuable measure of patients' perspectives toward being treated with low-density lipoprotein cholesterol-lowering therapies requiring subcutaneous injections. PMID- 26686785 TI - Reliability and Validity of the Work Instability Scale for Rheumatoid Arthritis. AB - OBJECTIVE: The objective was to evaluate the psychometric properties of the Rheumatoid Arthritis-Work Instability Scale (RA-WIS) in a clinical trial setting. METHODS: Secondary analyses were conducted using data from a 56-week, randomized controlled trial of patients with early rheumatoid arthritis (RA). Patient reported outcome measures included the RA-WIS, the Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Quality of Life Questionnaire, and the Global Assessment of Disease Activity and Pain, data for which were collected at baseline and at weeks 12, 16, 24, and 56. Data were analyzed for reliability, validity, and responsiveness. RESULTS: Among 148 patients whose data were analyzed, more than half were women (56.1%) with a mean age of 46.8 years. On average, patients experienced RA symptoms for 8.7 months; the mean 28-Joint Disease Activity Score (DAS28) was 5.9, and the mean HAQ - Disability Index was 1.3. The RA-WIS demonstrated excellent internal consistency and test-retest reliability (alpha = 0.89 and intraclass correlation coefficient = 0.91, respectively). At baseline and week 24, moderate to strong correlations were seen between RA-WIS total scores and the HAQ, the Global Assessment of Disease Activity, and the Pain Rheumatoid Arthritis Quality of Life Questionnaire, ranging from 0.47 to 0.81 (all P < 0.0001). Mean RA-WIS total scores and work disability risk levels discriminated between clinical severity scores on the DAS28, the HAQ - Disability Index, and the Physician Global Assessment of Disease Activity (all P < 0.05). Mean baseline to week 24 RA-WIS total change scores were significantly different among American College of Rheumatology responder groups (P <= 0.0001) and between DAS28 remission status groups (P < 0.001). CONCLUSIONS: These findings provide evidence supporting the reliability, validity, and responsiveness of the RA-WIS for evaluating work disability in patients with RA in a clinical trial setting. PMID- 26686786 TI - A Quality-Adjusted Life-Year Measure for Multiple Sclerosis: Developing a Patient Reported Health State Classification System for a Multiple Sclerosis-Specific Preference-Based Measure. AB - BACKGROUND: Increasingly, generic preference-based measures of health-related quality of life (HRQOL) are used to estimate quality-adjusted life-years to inform resource allocation decisions. Evidence suggests that generic measures may not be appropriate for multiple sclerosis (MS). OBJECTIVES: To report the first stage in the development of an MS-specific preference-based measure to quantify the impact of MS and its treatment: deriving a health state classification system, which is amenable to valuation, from the 29-item Multiple Sclerosis Impact Scale (MSIS-29), a widely used patient-reported outcome measure in MS. METHODS: The dimensional structure of the MSIS-29 was determined using factor analysis and a conceptual framework of HRQOL in MS. Item performance was assessed, using Rasch analysis and psychometric criteria, to enable the selection of one item to represent each dimension of HRQOL covered by the MSIS-29. Analysis was undertaken using a sample (N = 529) from a longitudinal study of people with MS. Results were validated by repeating the analysis with a second sample (N = 528). RESULTS: Factor analysis confirmed the two-subscale structure of the MSIS 29. Both subscales covered several conceptually independent dimensions of HRQOL. Following Rasch and psychometric analysis, an eight-dimensional classification system named the MSIS-8D was developed. Each dimension was represented by one item with four response levels. CONCLUSIONS: Combining factor analysis with conceptual mapping, and Rasch analysis with psychometric criteria, provides a valid method of constructing a classification system for an MS-specific preference-based measure. The next stage is to obtain preference weights so that the measure can be used in studies investigating MS. PMID- 26686787 TI - Estimating a Preference-Based Index for an Eight-Dimensional Health State Classification System for Multiple Sclerosis. AB - BACKGROUND: Condition-specific measures are frequently used to assess the health related quality of life of people with multiple sclerosis (MS). Such measures are unsuitable for use in economic evaluations that require estimates of cost per quality-adjusted life-year because they are not based on preferences. OBJECTIVES: To report the estimation of a preference-based single index for an eight dimensional instrument for MS, the Multiple Sclerosis Impact Scale - Eight Dimensions (MSIS-8D), derived from an MS-specific measure of health-related quality of life, the 29-item Multiple Sclerosis Impact Scale (MSIS-29). METHODS: We elicited preferences for a sample of MSIS-8D states (n = 169) from a sample (n = 1702) of the UK general population. Preferences were elicited using the time trade-off technique via an Internet-based survey. We fitted regression models to these data to estimate values for all health states described by the MSIS-8D. Estimated values were assessed against MSIS-29 scores and values derived from generic preference-based measures in a large, representative sample of people with MS. RESULTS: Participants reported that the time trade-off questions were easy to understand. Observed health state values ranged from 0.08 to 0.89. The best-performing model was a main effects, random effects model (mean absolute error = 0.04). Validation analyses support the performance of the MSIS-8D index: it correlated more strongly than did generic measures with MSIS-29 scores, and it discriminated effectively between subgroups of people with MS. CONCLUSIONS: The MSIS-8D enables health state values to be estimated from the MSIS-29, adding to the methods available to assess health outcomes and to estimate quality-adjusted life-years for MS for use in health technology assessment and decision-making contexts. PMID- 26686788 TI - A Vision "Bolt-On" Item Could Increase the Discriminatory Power of the EQ-5D Index Score. AB - BACKGROUND: Recently, a vision "bolt-on" EuroQol five-dimensional questionnaire (EQ-5D) was developed and tentative utility values (i.e., a "value set") for this new descriptive system were estimated. OBJECTIVES: To compare the discriminatory power of this bolt-on and standard utility-based EQ-5D health indices. METHODS: Cross-sectional data on the (3-level) vision bolt-on EQ-5D were collected through face-to-face interviews with 500 and 336 individuals with and without visual impairment, respectively. To assess the discriminatory power of the vision bolt on index relative to the standard EQ-5D index developed in the vision bolt-on valuation study, 16 pairs of mutually exclusive subgroups of individuals defined by the individuals' visual acuity and responses to the 14-item visual function questionnaire were compared pairwise. The absolute mean difference in the two index scores and the corresponding F statistic derived from the comparisons were used as measures of discriminatory power. RESULTS: The absolute mean difference in the bolt-on index score was larger than that in the standard EQ-5D index score in 14 of the 16 comparisons. The bolt-on index score exhibited a larger F statistic value than did the standard EQ-5D index score in all known-group comparisons, with the F-statistic ratio ranging from 0.415 to 0.770. CONCLUSIONS: The vision bolt-on EQ-5D appears to be more discriminative than the standard EQ 5D in measurement of vision problems. Future studies should investigate the extent to which the vision bolt-on item can increase the sensitivity of the EQ-5D to vision change in interventional studies. PMID- 26686789 TI - Quality of Life and Asthma Symptom Control: Room for Improvement in Care and Measurement. AB - BACKGROUND: The recent Global Initiative for Asthma management strategy recommends achieving symptom control and minimizing the future risk of poor outcomes as priorities for asthma management. OBJECTIVE: The objective was to quantify the association between symptom control and health-related quality of life in asthma. METHODS: In a prospectively recruited random sample of adults with asthma, we ascertained symptom control and measured health-related quality of life using a generic (EuroQol five-dimensional questionnaire [EQ-5D]) and a disease-specific (Asthma Quality of Life Questionnaire) instrument, to estimate EQ-5D and five-dimensional Asthma Quality of Life Questionnaire (AQL-5D) utilities, respectively. We measured the adjusted difference in utilities across symptom control levels and calculated the loss of predictive efficiency due to aggregating multiple symptoms into one symptom control variable. RESULTS: The final sample included 958 observations from 494 individuals (mean age at baseline 52.2 +/- 14.5 years; 67.0% women). Asthma was symptomatically controlled, partially controlled, and uncontrolled in 269 (28.1%), 367 (38.3%), and 322 (33.6%) observations, respectively. A person with symptomatically uncontrolled asthma would gain 0.0512 (95% CI 0.0339-0.0686) in EQ-5D or 0.0802 (95% CI 0.0693 0.0910) in AQL-5D utilities by achieving symptom control. The loss of predictive efficiency was 55.4% and 27.6% for EQ-5D and AQL-5D utilities, respectively. CONCLUSIONS: Asthma symptom control status corresponds well with both generic and disease-specific quality-of-life measures. The trade-off, however, between ease of use and predictive power should be reconsidered in developing simplified measures of control. Our results have direct relevance in informing decision analytic models of asthma and deducing the effect of interventions on quality of life through their impact on asthma control. PMID- 26686790 TI - Citizens' Perspectives on Disinvestment from Publicly Funded Pathology Tests: A Deliberative Forum. AB - BACKGROUND: Deliberative forums can be useful tools in policy decision making for balancing citizen voice and community values against dominant interests. OBJECTIVE: To describe the use of a deliberative forum to explore community perspectives on a complex health problem-disinvestment. METHODS: A deliberative forum of citizens was convened in Adelaide, South Australia, to develop criteria to support disinvestment from public funding of ineffective pathology tests. The case study of potential disinvestment from vitamin B12/folate pathology testing was used to shape the debate. The forum was informed by a systematic review of B12/folate pathology test effectiveness and expert testimony. RESULTS: The citizens identified seven criteria: cost of the test, potential impact on individual health/capacity to benefit, potential cost to society, public good, alternatives to testing, severity of the condition, and accuracy of the test. The participants not only saw these criteria as an interdependent network but also questioned "the authority" of policymakers to make these decisions. CONCLUSIONS: Coherence between the criteria devised by the forum and those described by an expert group was considerable, the major differences being that the citizens did not consider equity issues and the experts neglected the "cost" of social and emotional impact of disinvestment on users and the society. PMID- 26686791 TI - Comparison of Benefit-Risk Assessment Methods for Prospective Monitoring of Newly Marketed Drugs: A Simulation Study. AB - OBJECTIVES: To compare benefit-risk assessment (BRA) methods for determining whether and when sufficient evidence exists to indicate that one drug is favorable over another in prospective monitoring. METHODS: We simulated prospective monitoring of a new drug (A) versus an alternative drug (B) with respect to two beneficial and three harmful outcomes. We generated data for 1000 iterations of six scenarios and applied four BRA metrics: number needed to treat and number needed to harm (NNT|NNH), incremental net benefit (INB) with maximum acceptable risk, INB with relative-value-adjusted life-years, and INB with quality-adjusted life-years. We determined the proportion of iterations in which the 99% confidence interval for each metric included and excluded the null and we calculated mean time to alerting. RESULTS: With no true difference in any outcome between drugs A and B, the proportion of iterations including the null was lowest for INB with relative-value-adjusted life-years (64%) and highest for INB with quality-adjusted life-years (76%). When drug A was more effective and the drugs were equally safe, all metrics indicated net favorability of A in more than 70% of the iterations. When drug A was safer than drug B, NNT|NNH had the highest proportion of iterations indicating net favorability of drug A (65%). Mean time to alerting was similar among methods across the six scenarios. CONCLUSIONS: BRA metrics can be useful for identifying net favorability when applied to prospective monitoring of a new drug versus an alternative drug. INB-based approaches similarly outperform unweighted NNT|NNH approaches. Time to alerting was similar across approaches. PMID- 26686792 TI - Prospective Benefit-Risk Monitoring of New Drugs for Rapid Assessment of Net Favorability in Electronic Health Care Data. AB - BACKGROUND: Benefit-risk assessment (BRA) methods can combine measures of benefits and risks into a single value. OBJECTIVES: To examine BRA metrics for prospective monitoring of new drugs in electronic health care data. METHODS: Using two electronic health care databases, we emulated prospective monitoring of three drugs (rofecoxib vs. nonselective nonsteroidal anti-inflammatory drugs, prasugrel vs. clopidogrel, and denosumab vs. bisphosphonates) using a sequential propensity score-matched cohort design. We applied four BRA metrics: number needed to treat and number needed to harm; incremental net benefit (INB) with maximum acceptable risk; INB with relative-value-adjusted life-years; and INB with quality-adjusted life-years (QALYs). We determined whether and when the bootstrapped 99% confidence interval (CI) for each metric excluded zero, indicating net favorability of one drug over the other. RESULTS: For rofecoxib, all four metrics yielded a negative value, suggesting net favorability of nonselective nonsteroidal anti-inflammatory drugs over rofecoxib, and the 99% CI for all but the number needed to treat and number needed to harm excluded the null during follow-up. For prasugrel, only the 99% CI for INB-QALY excluded the null, but trends in values over time were similar across the four metrics, suggesting overall net favorability of prasugrel versus clopidogrel. The 99% CI for INB-relative-value-adjusted life-years and INB-QALY excluded the null in the denosumab example, suggesting net favorability of denosumab over bisphosphonates. CONCLUSIONS: Prospective benefit-risk monitoring can be used to determine net favorability of a new drug in electronic health care data. In three examples, existing BRA metrics produced qualitatively similar results but differed with respect to alert generation. PMID- 26686793 TI - Cost-Effectiveness of Chemotherapy for Breast Cancer and Age Effect in Older Women. AB - BACKGROUND: Previous economic evaluations compared specific chemotherapy agents using input parameters from clinical trials and resource utilization costs. Cost effectiveness of treatment groups (drug classes) using community-level effectiveness and cost data, however, has not been assessed for elderly patients with breast cancer. OBJECTIVE: To assess the cost-effectiveness of chemotherapy regimens by age and disease stage under "real-world" conditions for patients with breast cancer. METHODS: The Surveillance Epidemiology and End Results-Medicare data were used to identify patients with breast cancer with American Joint Committee on Cancer stage I/II/IIIa, hormone receptor-negative (estrogen receptor negative and progesterone receptor-negative) patients from 1992 to 2009. Patients were categorized into three adjuvant treatment groups: 1) no chemotherapy, 2) anthracycline, and 3) non-anthracycline-based chemotherapy. Median life-years and quality-adjusted life-years (QALYs) were measured using Kaplan-Meier analysis and were evaluated against average total health care costs (2013 US dollars). RESULTS: A total of 4575 patients (propensity score-matched) were included for the primary analysis. The anthracycline group experienced 12.05 QALYs and mean total health care costs of $119,055, resulting in an incremental cost effectiveness ratio of $7,688 per QALY gained as compared with the no chemotherapy group (QALYs 7.81; average health care cost $86,383). The non anthracycline-based group was dominated by the anthracycline group with lower QALYs (9.56) and higher health care costs ($122,791). Base-case results were found to be consistent with the best-case and worst-case scenarios for utility assignments. Incremental cost-effectiveness ratios varied by age group (range $3,790-$90,405 per QALY gained). CONCLUSIONS: Anthracycline-based chemotherapy was found cost-effective for elderly patients with early stage (stage I, II, IIIa) breast cancer considering the US threshold of $100,000 per QALY. Further research may be needed to characterize differential effects across age groups. PMID- 26686794 TI - Economic Evaluation of Cinacalcet in the United States: The EVOLVE Trial. AB - BACKGROUND: Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies. OBJECTIVES: The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective. METHODS: We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and $79,562 per quality-adjusted life year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of $115,876 per QALY. The model was most sensitive to the treatment effect on mortality. CONCLUSIONS: In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis. PMID- 26686795 TI - Using Decision-Analytic Modeling to Isolate Interventions That Are Feasible, Efficient and Optimal: An Application from the Norwegian Cervical Cancer Screening Program. AB - BACKGROUND: Decision makers often need to simultaneously consider multiple criteria or outcomes when deciding whether to adopt new health interventions. OBJECTIVES: Using decision analysis within the context of cervical cancer screening in Norway, we aimed to aid decision makers in identifying a subset of relevant strategies that are simultaneously efficient, feasible, and optimal. METHODS: We developed an age-stratified probabilistic decision tree model following a cohort of women attending primary screening through one screening round. We enumerated detected precancers (i.e., cervical intraepithelial neoplasia of grade 2 or more severe (CIN2+)), colposcopies performed, and monetary costs associated with 10 alternative triage algorithms for women with abnormal cytology results. As efficiency metrics, we calculated incremental cost effectiveness, and harm-benefit, ratios, defined as the additional costs, or the additional number of colposcopies, per additional CIN2+ detected. We estimated capacity requirements and uncertainty surrounding which strategy is optimal according to the decision rule, involving willingness to pay (monetary or resources consumed per added benefit). RESULTS: For ages 25 to 33 years, we eliminated four strategies that did not fall on either efficiency frontier, while one strategy was efficient with respect to both efficiency metrics. Compared with current practice in Norway, two strategies detected more precancers at lower monetary costs, but some required more colposcopies. Similar results were found for women aged 34 to 69 years. CONCLUSIONS: Improving the effectiveness and efficiency of cervical cancer screening may necessitate additional resources. Although efficient and feasible, both society and individuals must specify their willingness to accept the additional resources and perceived harms required to increase effectiveness before a strategy can be considered optimal. PMID- 26686796 TI - Appropriateness of Prescriptions of Recommended Treatments in Organisation for Economic Co-operation and Development Health Systems: Findings Based on the Long Term Registry of the European Society of Cardiology on Heart Failure. AB - OBJECTIVE: This observational study aimed to identify clinical variables and health system characteristics associated with incomplete guideline application in drug treatment of patients with chronic heart failure (HF) across 15 countries. METHODS: Three data sets were used: European Society of Cardiology Heart Failure Registry, Organisation for Economic Co-operation and Development's Health System Characteristics Survey, and Organisation for Economic Co-operation and Development Health Statistics 2013. Patient and country variables were examined by multilevel, multiple logistic regression. The study population consisted of ambulatory patients with chronic HF and reduced ejection fraction. Inappropriateness of prescription of pharmacological treatments was defined as patients not prescribed at least one of the two recommended treatments (angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta blockers) or treated with both medications but at suboptimal dosage and in absence of documented contraindication/intolerance. RESULTS: Of 4605 patients, 1097 (23.8%) received inappropriate drug prescriptions with a large variation within and across countries, with 18.5% of the total variability accounted for by between-country health structure characteristics. Patient-level characteristics such as having mitral regurgitation (odds ratio 1.4; 95% confidence interval 1.1 1.7) was significantly associated with inappropriate prescription of recommended drugs, whereas chronic obstructive pulmonary disease (odds ratio 0.7; 95% confidence interval 0.5-0.9) was associated with more appropriate prescriptions. Among the country-level variables, incentives or obligation to comply with guidelines increased the probability of prescription appropriateness. CONCLUSIONS: Combining clinical variables with health system characteristics is a promising exercise to explain the appropriateness of recommended drug prescriptions. Such an understanding can help decision makers to design more effective policies to improve adherence to guidelines, improve health care outcomes, and potentially reduce costs. PMID- 26686797 TI - Time Series Analysis on the Impact of Generic Substitution and Reference Pricing on Antipsychotic Costs in Finland. AB - OBJECTIVES: To analyze the medium- to long-term impact of generic substitution and the reference price system on the daily cost of antipsychotics in Finland. The additional impact of reference pricing over and above previously implemented generic substitution was also assessed. METHODS: An interrupted time series design with a control group and segmented regression analysis was used to estimate the effect of the implementation of generic substitution and the reference price system on the daily cost of antipsychotics. The data have 69 monthly values of the average daily cost for each of the studied antipsychotics: 39 months before and 30 months after the introduction of reference pricing. For one of the studied antipsychotic, the time before the introduction of reference pricing could be further divided into time before and after the introduction of generic substitution. RESULTS: According to the model, 2.5 years after the implementation of reference pricing, the daily cost of the studied antipsychotics was 24.6% to 50.6% lower than it would have been if reference pricing had not been implemented. Two and a half years after the implementation of the reference price system, however, the additional impact of reference pricing over and above previously implemented generic substitution was modest, less than 1 percentage point. CONCLUSIONS: Although the price competition induced by reference pricing decreased the prices of antipsychotics in Finland in the short-term, the prices had a tendency to stagnate or even to turn in an upward direction in the medium- to long-term. Furthermore, the additional impact of reference pricing over and above previously implemented generic substitution remained quite modest. PMID- 26686798 TI - HIV Treatment in Resource-Limited Environments: Treatment Coverage and Insights. AB - BACKGROUND: The effects of antiretroviral treatment on the HIV epidemic are complex. HIV-infected individuals survive longer with treatment, but are less likely to transmit the disease. The standard coverage measure improves with the deaths of untreated individuals and does not consider the fact that some individuals may acquire the disease and die before receiving treatment, making it susceptible to overestimating the long-run performance of antiretroviral treatment programs. OBJECTIVE: The objective was to propose an alternative coverage definition to better measure the long-run performance of HIV treatment programs. METHODS: We introduced cumulative incidence-based coverage as an alternative to measure an HIV treatment program's success. To numerically compare the definitions, we extended a simulation model of HIV disease and treatment to represent a dynamic population that includes uninfected and HIV-infected individuals. Also, we estimated the additional resources required to implement various treatment policies in a resource-limited setting. RESULTS: In a synthetic population of 600,000 people of which 44,000 (7.6%) are infected, and eligible for treatment with a CD4 count of less than 500 cells/mm(3), assuming a World Health Organization (WHO)-defined coverage rate of 50% of eligible people, and treating these individuals with a single treatment regimen, the gap between the current WHO coverage definition and our proposed one is as much as 16% over a 10 year planning horizon. CONCLUSIONS: Cumulative incidence-based definition of coverage yields a more accurate representation of the long-run treatment success and along with the WHO and other definitions of coverage provides a better understanding of the HIV treatment progress. PMID- 26686799 TI - Using Generalized Linear Mixed Models to Evaluate Inconsistency within a Network Meta-Analysis. AB - BACKGROUND: Network meta-analysis compares multiple treatments by incorporating direct and indirect evidence into a general statistical framework. One issue with the validity of network meta-analysis is inconsistency between direct and indirect evidence within a loop formed by three treatments. Recently, the inconsistency issue has been explored further and a complex design-by-treatment interaction model proposed. OBJECTIVE: The aim of this article was to show how to evaluate the design-by-treatment interaction model using the generalized linear mixed model. METHODS: We proposed an arm-based approach to evaluating the design by-treatment inconsistency, which is flexible in modeling different types of outcome variables. We used the smoking cessation data to compare results from our arm-based approach with those from the standard contrast-based approach. RESULTS: Because the contrast-based approach requires transformation of data, our example showed that such a transformation may yield biases in the treatment effect and inconsistency evaluation, when event rates were low in some treatments. We also compared contrast-based and arm-based models in the evaluation of design inconsistency when different heterogeneity variances were estimated, and the arm based model yielded more accurate results. CONCLUSIONS: Because some statistical software commands can detect the collinearity among variables and automatically remove the redundant ones, we can use this advantage to help with placing the inconsistency parameters. This could be very useful for a network meta-analysis involving many designs and treatments. PMID- 26686800 TI - Health Utility Values Associated with Surgical Site Infection: A Systematic Review. AB - BACKGROUND: Surgical site infection (SSI) is a costly postoperative complication whose impact on patients' health-related quality of life is highly uncertain and has not been summarized to date. OBJECTIVE: The objective was to summarize the evidence base on SSI health utility values reported in patient-level studies and decision models. METHODS: A systematic review of SSI utility values reported in patient-level and decision modeling studies was carried out. Studies in which utility values for SSI were either invoked (e.g., model-based economic evaluations) or elicited (e.g., valuation exercises), or at least one non preference-based instrument was administered to patients with SSI after open surgery were included. Mapping algorithms were used, where appropriate, to calculate utilities from primary data. Results were summarized narratively, and the quality of the utility values used in the included modeling studies was assessed. RESULTS: Of 6552 records identified in the database search, 28 studies were included in the review: 19 model-based economic evaluations and 9 patient level studies. SSI utility decrements ranged from 0.04 to 0.48, of which 19 ranged from 0.1 to 0.3. SSI utility decrements could be calculated for three patient-level studies, and their values ranged from 0.05 (7 days postoperatively) to 0.124 (1 year postoperatively). In most modeling studies, SSI utilities were informed by authors' assumptions or by secondary sources. CONCLUSIONS: SSI may substantially affect patients' health utility and needs to be considered when modeling decision problems in surgery. The evidence base for SSI utilities is of questionable quality and skewed toward orthopedic surgery. Further research must concentrate on producing reliable estimates for patients without orthopedic problems. PMID- 26686801 TI - Beware of Kinked Frontiers: A Systematic Review of the Choice of Comparator Strategies in Cost-Effectiveness Analyses of Human Papillomavirus Testing in Cervical Screening. AB - OBJECTIVES: To systematically review the choice of comparator strategies in cost effectiveness analyses (CEAs) of human papillomavirus testing in cervical screening. METHODS: The PubMed, Web of Knowledge, and Scopus databases were searched to identify eligible model-based CEAs of cervical screening programs using human papillomavirus testing. The eligible CEAs were reviewed to investigate what screening strategies were chosen for analysis and how this choice might have influenced estimates of the incremental cost-effectiveness ratio (ICER). Selected examples from the reviewed studies are presented to illustrate how the omission of relevant comparators might influence estimates of screening cost-effectiveness. RESULTS: The search identified 30 eligible CEAs. The omission of relevant comparator strategies appears likely in 18 studies. The ICER estimates in these cases are probably lower than would be estimated had more comparators been included. Five of the 30 studies restricted relevant comparator strategies to sensitivity analyses or other subanalyses not part of the principal base-case analysis. Such exclusion of relevant strategies from the base-case analysis can result in cost-ineffective strategies being identified as cost effective. CONCLUSIONS: Many of the CEAs reviewed appear to include insufficient comparator strategies. In particular, they omit strategies with relatively long screening intervals. Omitting relevant comparators matters particularly if it leads to the underestimation of ICERs for strategies around the cost effectiveness threshold because these strategies are the most policy relevant from the CEA perspective. Consequently, such CEAs may not be providing the best possible policy guidance and lead to the mistaken adoption of cost-ineffective screening strategies. PMID- 26686802 TI - Health-Related Quality of Life and Health Utilities in Metastatic Castrate Resistant Prostate Cancer: A Survey Capturing Experiences from a Diverse Sample of UK Patients. AB - BACKGROUND: The collection of preference-based health outcomes data (or utility values) is required to support cost-effectiveness analyses. OBJECTIVE: This study aimed to collect health-related quality of life (HRQOL) data in men with metastatic castration-resistant prostate cancer (CRPC) stratified by disease states. METHODS: Men with metastatic CRPC were recruited via UK patient associations, patient panels, and specialist recruiters and classified into four subgroups reflecting disease state: asymptomatic/mildly symptomatic before chemotherapy, symptomatic before chemotherapy, receiving chemotherapy, and postchemotherapy. HRQOL data (including five-level EuroQol five-dimensional questionnaire [EQ-5D-5L], European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30], and 25-item prostate cancer-specific questionnaire module designed to supplement the EORTC QLQ-C30) along with background and medical history data were collected via an online survey. The EQ-5D-5L and the EORTC-8D (EORTC-8D is an 8 dimensional utility index scored from QLQ-C30 data) were both used to estimate utilities. RESULTS: Data were collected from a total sample of 163 men with metastatic CRPC. Utility values elicited by the EQ-5D-5L ranged from 0.830 for the asymptomatic/mildly symptomatic before chemotherapy disease state (95% confidence interval [CI] 0.795 0.865) to 0.625 for the symptomatic before chemotherapy disease state (95% CI 0.577-0.673). EORTC-8D utilities ranged from 0.856 (95% CI 0.831-0.882) to 0.697 (95% CI 0.664-0.731) for the same disease/treatment states. CONCLUSIONS: This online survey was designed to capture real-world HRQOL data describing men with CRPC. The study estimated utilities using two alternative methods, and the results show good agreement, suggesting that they are robust. This methodology offers a potentially higher quality alternative to vignette-based methods that are commonly used in oncology submissions. PMID- 26686803 TI - Long-Term Efficacy of Etanercept for Plaque-Type Psoriasis and Estimated Cost in Daily Clinical Practice. AB - BACKGROUND: There are numerous clinical trials proving efficacy and safety profiles of etanercept. Newer studies, however, include patients with significant comorbidities, unstable psoriasis, or concomitant treatments. OBJECTIVE: The objective of this study was to provide data on long-term response to etanercept and estimate the cost in daily practice. METHODS: This is an observational retrospective study including patients with plaque-type psoriasis receiving etanercept 50 mg/wk for more than 6 months at the Dermatology Department of the University Hospital of La Coruna (Spain). Psoriasis severity was determined using the Psoriasis Area and Severity Index (PASI) at baseline and then at 12 weeks, 24 weeks, and annually until treatment discontinuation. RESULTS: A total of 102 patients aged 24 to 78 years were included. Response rates of 58.8% and 66.3% for PASI 75 score (reduction of at least 75% in PASI score compared with baseline) were achieved after 12 and 24 weeks of treatment, respectively. Among patients who continued treatment, the PASI 75 score was maintained by 75.3% at 1 year, 82.5% at 2 years, and 88.2% at 3 years. The percentage of patients receiving other systemic treatments was 38.2%. Adverse effects were reported in 13.7%, all of them mild, except one case of urinary sepsis. The average cost per patient was ?244.68 +/- ?45.27 per week and ?34.95 +/- ?6.46 per day. CONCLUSIONS: We provide data on long-term response to etanercept and its costs in a real-world setting. Response rates were higher than in some clinical trials, with progressive efficacy and not related to body mass index. Etanercept cost was comparable with that estimated in other studies. Combination with a conventional systemic agent can enhance efficacy without additional adverse events. PMID- 26686804 TI - Synthesis and electrochemical properties of Li(1.3)Nb(0.3)V(0.4)O2 as a positive electrode material for rechargeable lithium batteries. AB - The binary system, xLi3NbO4-(1 - x)LiVO2, was first examined as an electrode material for rechargeable lithium batteries. The sample (x = 0.43) crystallizes into a cation-disordered rocksalt structure and delivers a reversible capacity of ca. 230 mA h g(-1), which originates from V(3+)/V(5+) redox with electrochemically inactive niobium ions. PMID- 26686805 TI - SCAI/ACC/HRS institutional and operator requirements for left atrial appendage occlusion. PMID- 26686806 TI - Hypothenar hammer syndrome: long-term follow-up after ulnar artery reconstruction with the lateral circumflex femoral artery. AB - : In symptomatic patients with hypothenar hammer syndrome, the occluded part of the ulnar artery can be reconstructed with an autologous graft. Venous grafts are used frequently, but they are known for their low patency rate. Arterial grafts show better patency rates than venous grafts in coronary bypass surgery. We performed 11 ulnar artery reconstructions with the descending branch of the lateral circumflex femoral artery and compared these with previously performed venous reconstructions. All patients with an arterial graft reconstruction had a patent graft at a mean follow-up of 63 months. In addition, nine out of 11 patients reported improvement in their symptoms. The patency rate of venous reconstructions in hypothenar hammer syndrome is significantly lower. Arterial grafting for hypothenar hammer syndrome has superior patency compared with venous grafting; we recommend it as the surgical treatment of choice for symptomatic hypothenar hammer syndrome. LEVEL OF EVIDENCE: 4. PMID- 26686807 TI - The contribution of Mycoplasma genitalium to the aetiology of sexually acquired infectious proctitis in men who have sex with men. AB - This study examined the contribution of Mycoplasma genitalium to sexually acquired infectious proctitis in men who have sex with men (MSM). MSM with symptomatic proctitis between May 2012 and August 2013 were tested for rectal sexually transmitted infections including chlamydia, gonorrhoea, herpes simplex virus (HSV) and M. genitalium. The load of rectal M. genitalium in men with symptomatic proctitis was compared with a separate group of men who had rectal M. genitalium but no symptoms of proctitis. Among 154 MSM with proctitis, rectal M. genitalium was detected in 18 men (12%, 95% CI 6.9-17.1) and was significantly more common among human immunodeficiency virus (HIV) -positive men (21%, 95% CI 9.5-32.6) than HIV-negative men (8%, 95% CI 2.9-13.1; prevalence ratio 3.2, 95% CI 1.2-8.8). Among HIV-positive men the detection of M. genitalium was comparable to that for chlamydia (21%, 95% CI 9.5-32.5), gonorrhoea (25%, 95% CI 16.2-41.8) and HSV (19%, 95% CI 7.9-30.1). Rectal M. genitalium load was significantly higher among the 18 men with symptomatic M. genitalium-associated proctitis than among a separate group of 18 men with asymptomatic rectal M. genitalium infection (60 000 copies of organism/swab versus 10 744 copies of organism/swab, p 0.023). Comprehensive testing for rectal pathogens in MSM with proctitis should include testing for M. genitalium. PMID- 26686808 TI - Campylobacteriosis: the role of poultry meat. AB - The incidence of human infections caused by Campylobacter jejuni and Campylobacter coli, the main bacterial agents of gastrointestinal disease, has been increasing worldwide. Here, we review the role of poultry as a source and reservoir for Campylobacter. Contamination and subsequent colonization of broiler flocks at the farm level often lead to transmission of Campylobacter along the poultry production chain and contamination of poultry meat at retail. Yet Campylobacter prevalence in poultry, as well as the contamination level of poultry products, vary greatly between different countries so there are differences in the intervention strategies that need to be applied. Temporal patterns in poultry do not always coincide with those found in human infections. Studies in rural and urban areas have revealed differences in Campylobacter infections attributed to poultry, as poultry seems to be the predominant reservoir in urban, but not necessarily in rural, settings. Furthermore, foreign travel is considered a major risk factor in acquiring the disease, especially for individuals living in the northern European countries. Intervention strategies aimed at reducing Campylobacter colonization in poultry and focused at the farm level have been successful in reducing the number of Campylobacter cases in several countries. Increasing farm biosecurity and education of consumers are likely to limit the risk of infection. Overall, poultry is an important reservoir and source of human campylobacteriosis, although the contribution of other sources, reservoirs and transmission warrants more research. PMID- 26686809 TI - Diversity and combinations of infectious agents in 38 adults with an infection triggered reactive haemophagocytic syndrome: a multicenter study. AB - Reactive haemophagocytic syndrome (HS) is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Although various microorganisms are thought to trigger HS, most of the literature data on this topic have been gathered in single-centre case series. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients with HS. Patients were included in the present study if HS was solely due to one or more infections. Detailed microbiological data were recorded. Of the 162 patients with HS in the cohort, 40 (25%) had at least one infection and 38 of the latter (including 14 women, 36.8%) were included. The median age was 46 years. Seven patients were presumed to be immunocompetent (18.4%), whereas 19 patients (50%) were infected with human immunodeficiency virus and 12 patients (31.6%) were immunocompromised for other reasons. Twenty-seven patients (71.1%) had a single infection, whereas six (15.8%) and five (13.1%) patients had, respectively, two and three concomitant infections. We observed pyogenic bacterial infections (n = 7), tuberculosis (n = 10), non-tuberculous mycobacteriosis (n = 3), viral infections (n = 17: 11 cytomegalovirus, three Epstein-Barr virus, two human herpesvirus 8, one herpes simplex virus 2), parasitic infections (n = 8: four disseminated toxoplasmosis, one leishmaniasis, three malaria), fungal infections (n = 5: four pulmonary pneumocystosis and one candidaemia). Eighteen patients (47.4%) received corticosteroids and/or etoposide. Twelve patients died (31.6%). All multiple infections and all deaths occurred in immunocompromised patients. When compared with patients suffering from malignancy-associated HS, patients with infection-triggered HS were younger and more likely to be immunocompromised, and had a better outcome. PMID- 26686810 TI - A one-year survey of Microsporum audouinii infections in Belgium: epidemiological and genotypic characterization. AB - During recent years the proportion of tinea capitis infections due to Microsporum audouinii has increased in both Belgium and other European countries. To better understand the emergence of this species, the Belgian National Reference Centre for dermatophytes launched an epidemiological survey on the main anthropophilic dermatophytes causing tinea capitis in Belgium and included the genomic characterization of M. audouinii isolates. In total, 116 strains of M. audouinii were confirmed and characterized by the DiversiLab((r)) system (bioMerieux). Six genotypic variants were identified, among which one major group included 90 isolates and the reference strain. Another variant group (11 strains) was exclusively confined to a geographical region in south Belgium. Analysis of epidemiological characteristics of the infected population showed that the main age category was 5- to 9-year-old children with a sex ratio (male/female) of 1.97. Data concerning the geographic origin of the family revealed a majority of Belgian nationality (44.7%), suggesting that the infection originated in Belgium. Other nationalities were primarily African. At this time, no clear correlation has been established between one particular strain and a specific country of origin. PMID- 26686811 TI - Contamination of Australian newborn calf carcasses at slaughter with Clostridium difficile. AB - In North America and Europe, reports of a genetic overlap between toxigenic strains of Clostridium difficile isolated from humans, livestock and retail meat suggest that food-borne transmission may be occurring. We investigated the prevalence, concentration and genetic diversity of C. difficile on the carcasses (n = 300) and in the faeces (n = 30) of neonatal veal calves at three abattoirs in Australia in 2013. Selective culture (both direct and enrichment) was performed, and all isolates were characterized by PCR for the toxin genes tcdA, tcdB and cdtA/B and by PCR ribotyping. Prevalence of C. difficile was 25.3% (76/300) on carcasses and 60.0% (18/30) in faeces. Multiple PCR ribotypes (RT) were detected, with four binary toxin-positive RTs accounting for 70.3% (71/101) of isolates; 127 (A(+), B(+), CDT(+), 32.7%), 288 (A(-), B(-), CDT(+), 28.7%), 033 (A(-), B(-), CDT(+), 6.9%) and 126 (A(+), B(+), CDT(+), 2.0%). Viable counts of a subset of samples revealed detectable numbers of C. difficile in 66.7% (10/15) of faecal samples (range 2.0 * 10(3) to 2.3 * 10(6) CFU/mL, median count 2.5 * 10(4) CFU/mL) and in 16.7% (25/150) of carcase samples (range 3 to 33 CFU/cm(2), median count 7 CFU/cm(2)). These data further confirm that Australian neonatal veal calf carcasses are contaminated with potentially significant strains of C. difficile at slaughter. PMID- 26686812 TI - Poultry food products--a source of avian influenza virus transmission to humans? AB - Global human mobility and intercontinental connectivity, expansion of livestock production and encroachment of wildlife habitats by invasive agricultural land use contribute to shape the complexity of influenza epidemiology. The OneHealth approach integrates these and further elements into considerations to improve disease control and prevention. Food of animal origin for human consumption is another integral aspect; if produced from infected livestock such items may act as vehicles of spread of animal pathogens, and, in case of zoonotic agents, as a potential human health hazard. Notifiable zoonotic avian influenza viruses (AIV) have become entrenched in poultry populations in several Asian and northern African countries since 2003. Highly pathogenic (HP) AIV (e.g. H5N1) cause extensive poultry mortality and severe economic losses. HPAIV and low pathogenic AIV (e.g. H7N9) with zoonotic propensities pose risks for human health. More than 1500 human cases of AIV infection have been reported, mainly from regions with endemically infected poultry. Intense human exposure to AIV-infected poultry, e.g. during rearing, slaughtering or processing of poultry, is a major risk factor for acquiring AIV infection. In contrast, human infections through consumption of AIV-contaminated food have not been substantiated. Heating poultry products according to kitchen standards (core temperatures >=70 degrees C, >=10 s) rapidly inactivates AIV infectivity and renders fully cooked products safe. Nevertheless, concerted efforts must ensure that poultry products potentially contaminated with zoonotic AIV do not reach the food chain. Stringent and sustained OneHealth measures are required to better control and eventually eradicate, HPAIV from endemic regions. PMID- 26686814 TI - Editor's summary. PMID- 26686813 TI - Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age. AB - The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People's Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID- 26686815 TI - Challenging the system. PMID- 26686816 TI - Chemotherapy-Induced Nausea and Vomiting: A Narrative Review to Inform Dietetics Practice. AB - Chemotherapy-induced nausea and vomiting (CINV) are common symptoms experienced by patients with cancer that influence nutrition. They exert a detrimental effect on dietary intake, risk of malnutrition, and quality of life. Whereas CINV are primarily managed with medication, nutrition and dietetics practitioners play an important role in the management of CINV-related complications such as reduced dietary intake. This review discusses the burden of nausea and vomiting that patients with cancer can experience, including the effect on quality of life, nutritional status, and treatment outcomes. Implications for dietetics practice include the need to explore the nature of reported symptoms, identify predisposing risk factors, and to consider the use of a variety of interventions that are individualized to a patient's symptoms. There are little clinical data regarding effective dietetic interventions for nausea and vomiting. In summary, this review discusses dietetics-related issues surrounding CINV, including the pathophysiology, risk factors, prevalence, and both pharmacologic and dietetic treatment options. PMID- 26686817 TI - Diets High in Fiber and Vegetable Protein Are Associated with Low Lumbar Bone Mineral Density in Young Athletes with Oligoamenorrhea. AB - BACKGROUND: Associations of bone mineral density (BMD) with specific food components, including dietary fiber and isoflavones (that have a negative association with serum estrogen), are unclear and need to be determined, particularly in populations more likely to consume large amounts of these nutrients (such as young athletes). OBJECTIVE: To determine dietary intake of specific food components in athletes with oligoamenorrhea (OA) compared to athletes with eumenorrhea (EA) and nonathletes (NA), and associations of the dietary intake of these nutrients with lumbar spine BMD. DESIGN AND SUBJECTS: This cross-sectional study evaluated 68 OA, 24 EA, and 26 NA individuals aged 14 to 23 years. Measurements included 4-day food records, a dual x-ray absorptiometry scan evaluating lumbar spine BMD and body composition, and hormone levels. Multivariate analysis was used to estimate associations of nutrients with lumbar spine BMD. RESULTS: Compared with EA and NA, OA had higher intake of fiber, phytic acid, and vegetable protein (all P values <0.0001). Intake of isoflavones, genistein, and daidzein was higher in OA than NA (P=0.003 and P=0.0002, respectively). OA had lower consumption of energy from saturated fatty acids than NA (P=0.002). After controlling for confounders such as body weight, menstrual status (indicative of estrogen status), calcium intake, and serum vitamin D (known BMD determinants), lumbar spine BMD z scores were inversely associated with dietary fiber (beta=-.30; P=0.01), vegetable protein (beta= -.28; P=0.02), phytic acid (beta=-.27; P=0.02), genistein (beta=-.25; P=0.01), and daidzein (beta=-.24; P=0.01), and positively associated with percent energy from fatty acids (beta=.32; P=0.0006). CONCLUSIONS: Compared with EA and NA, OA had a higher dietary intake of fiber, vegetable protein, and phytic acid, which were inversely associated with lumbar spine BMD z scores. Further studies are needed to assess dietary recommendations for OA to optimize bone accrual. PMID- 26686818 TI - Beverage Choices of Adolescents and Their Parents Using the Theory of Planned Behavior: A Mixed Methods Analysis. AB - BACKGROUND: Added sugar intake in the form of sugar-sweetened beverages (SSBs) has been considered a contributor to weight gain and cardiometabolic dysfunction in adults and youth. Adolescents are some of the highest consumers of added sugars, taking in ~16% of their total calories from added sugars with ~40% of these calories coming from SSBs. Food preferences and self-regulation of dietary intake by youth can be influenced by parents. OBJECTIVE: To evaluate the effectiveness of the Theory of Planned Behavior (TPB) in understanding and predicting adolescents' SSB consumption, identify which constructs are the most important when evaluating SSB consumption in adolescents, and determine whether and how adolescents' beverage choices are influenced by parents' reactions to their beverage choices. DESIGN: Measurements for this cross-sectional study included four record-assisted 24-hour dietary recalls and responses to an SSB specific TPB questionnaire from 100 adolescents. Consenting parents completed a beverage intake questionnaire, a TPB questionnaire, and the Parent Response to Beverage Choice Questionnaire. RESULTS: The TPB explained 34% of the variance in adolescents' and parents' intention to limit SSBs to <1cup/day. Parents' perceived behavioral control (b=1.35; P=0.002) and adolescents' subjective norms (b=0.57; P=0.001) were the strongest predictors of intention, and intention was the strongest predictor of SSB consumption in both adolescents and parents (b=-37 [P=0.026] and b=-49 [P=0.003], respectively). The TPB explained more variance in parent SSB consumption (R(2)=0.38) than adolescents (R(2)=0.22). Parents did more discouraging of SSBs and encouraging of non-SSBs. Adolescents' intention to limit SSB consumption moderated the relationship between parents' reactions encouraging SSBs and adolescents' predicted SSB consumption (P=0.021). CONCLUSIONS: The TPB explained a small but significant amount of variance in adolescents' SSB consumption. When addressing adolescent SSB intake, people in addition to parents may influence their intentions and SSB consumption. PMID- 26686819 TI - Proteomonas sulcata ACR1: A Fast Anion Channelrhodopsin. AB - Natural channelrhodopsins with strictly anion selectivity and high unitary conductance have been recently discovered in the cryptophyte alga Guillardia theta. These proteins, called anion channelrhodopsins (ACRs), are of interest for their novel function and also because they were shown to be highly efficient tools to inhibit neuronal action potentials with light. We show that a homologous protein from the cryptophyte alga Proteomonas sulcata (named here PsuACR1) exhibits similar strict anion selectivity as the previously identified G. theta ACRs. Like G. theta ACRs, PsuACR1 lacks a protonatable residue at the position of the proton acceptor Asp-85 in bacteriorhodopsin, which may be a key characteristic of ACR family members shared by haloarchaeal chloride pumps. Of importance for its potential use in optogenetics, despite its 10-fold lower channel activity than the GtACRs, PsuACR1 exhibits an ~eightfold more rapid channel closing half-time making it uniquely suitable for silencing the subclass of high-frequency firing neurons when high-time resolution is needed. The existence of a rhodopsin with properties similar to G. theta ACRs in a different cryptophyte genus indicates that such proteins may be widespread in the phylum of cryptophyte algae. PMID- 26686821 TI - Breed-specific factors influence embryonic lipid composition: comparison between Jersey and Holstein. AB - Some embryos exhibit better survival potential to cryopreservation than others. The cause of such a phenotype is still unclear and may be due to cell damage during cryopreservation, resulting from overaccumulation and composition of lipids. In cattle embryos, in vitro culture conditions have been shown to impact the number of lipid droplets within blastomeres. Thus far, the impact of breed on embryonic lipid content has not been studied. In the present study were compared the colour, lipid droplet abundance, lipid composition, mitochondrial activity and gene expression of in vivo-collected Jersey breed embryos, which are known to display poor performance post-freezing, with those of in vivo Holstein embryos, which have good cryotolerance. Even when housed and fed under the same conditions, Jersey embryos were found to be darker and contain more lipid droplets than Holstein embryos, and this was correlated with lower mitochondrial activity. Differential expression of genes associated with lipid metabolism and differences in lipid composition were found. These results show genetic background can impact embryonic lipid metabolism and storage. PMID- 26686820 TI - Transgenic expression of Dspp partially rescued the long bone defects of Dmp1 null mice. AB - Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1(-/-)) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1(-/-) mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as "Dmp1(-/-);Dspp-Tg mice"). We characterized the long bones of the Dmp1(-/-);Dspp-Tg mice at different ages and compared them with those from Dmp1( /-) and Dmp1(+/-) (normal control) mice. Our analyses showed that the long bones of Dmp1(-/-);Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1(-/-) mice. The long bones of Dmp1(-/ );Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1(-/-) mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1(-/-) mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that DSPP and DMP1 may function synergistically within the complex milieus of bone matrices. PMID- 26686822 TI - Root Canal Surface Strain and Canal Center Transportation Induced by 3 Different Nickel-Titanium Rotary Instrument Systems. AB - INTRODUCTION: Root canal anatomy and canal preparation instruments affect the outcome of endodontic treatment. The purpose of this study was to determine the root surface strain (SS) generated and the extent of canal center transportation during canal shaping using 3 different nickel-titanium instruments. METHODS: Simulated root canals in resin blocks (n = 10 per group) were prepared using adaptive rotary motion with twisted files (Twisted File Adaptive [TFA]; SybronEndo, Orange, CA), reciprocating rotary motion with WaveOne (WO; Dentsply Maillefer, Ballaigues, Switzerland) files, and continuous rotary motion with ProTaper Next files (PTN, Dentsply Maillefer). Electrical strain gauges at 3 sites recorded SS real time during canal shaping, and the blocks were scanned by micro-computed tomographic imaging to assess the canal center deviation at 3 sections after root canal instrumentation. The mean maximum SS and the canal center transportation for all groups and sites were derived and analyzed for a possible correlation between them. RESULTS: An overall increase in root SS was observed after root canal instrumentation. A significant difference in the induced mean maximum SS between TFA, WO, and PTN at specific sites of curved root canals was observed. A statistically significant difference in the mean distance of canal center transportation was observed among the 3 shaping techniques at the apical section. Finally, the mean maximum SS values induced during canal shaping strongly correlated with canal center transportation in the apical section and the coronal section. CONCLUSIONS: The curved canals prepared using TFA exhibited lower SS and less canal center transportation at the apical section than the WO and PTN systems. SS generated during canal shaping correlated with canal center transportation in a site-specific manner. PMID- 26686823 TI - Systemically Transplanted Bone Marrow-derived Cells Contribute to Dental Pulp Regeneration in a Chimeric Mouse Model. AB - INTRODUCTION: Migratory cells via blood circulation or cells adjacent to the root apex may potentially participate in dental pulp tissue regeneration or renewal. This study investigated whether systemically transplanted bone marrow cells can contribute to pulp regeneration in a chimeric mouse model. METHODS: A chimeric mouse model was created through the injection of bone marrow cells from green fluorescent protein (GFP) transgenic C57BL/6 mice into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 8.5 Gy from a high-frequency linear accelerator. These mice were subjected to pulpectomy and pulp revascularization. At 1, 4, and 8 weeks after surgery, in vivo animal imaging and histologic analyses were conducted. RESULTS: In vivo animal imaging showed that the green biofluorescence signal from the transplanted GFP+ cells increased significantly and was maintained at a high level during the first 4 weeks after surgery. Immunofluorescence analyses of tooth specimens collected at 8 weeks postsurgery showed the presence of nestin+/GFP+, alpha smooth muscle actin (alpha-SMA)/GFP+, and NeuN/GFP+ cells within the regenerated pulplike tissue. CONCLUSIONS: These data confirm that transplanted bone marrow derived cells can contribute to dental pulp regeneration. PMID- 26686824 TI - Prognostic Factors for Clinical Outcomes in Autotransplantation of Teeth with Complete Root Formation: Survival Analysis for up to 12 Years. AB - INTRODUCTION: Tooth autotransplantation is a treatment option that has the potential to restore masticatory function and esthetics to edentulous spaces resulting from extracted teeth. The purpose of this study was to investigate the prognostic factors and clinical outcomes for autotransplanted teeth with complete root formation. METHODS: Patients who had received tooth autotransplantation in the Department of Conservative Dentistry, Yonsei University Dental Hospital, Seoul, Korea, from July 2001 to August 2010 were electronically searched, and a total of 105 cases of autotransplanted teeth met the inclusion criteria. Tooth survival, inflammatory root resorption (IRR), ankylosis, and related prognostic factors were assessed by using the survival analysis that was based on clinical and radiographic examination. RESULTS: The cumulative tooth survival rate was 68.2% at 12 years after the tooth autotransplantation. According to the Cox proportional hazard regression analysis, patient age, donor position, and extraoral time were significantly associated with tooth survival (P < .05). Donor extraction type was significantly associated with IRR (P < .05), and transplantation timing and initial stability were significantly associated with ankylosis (P < .05) CONCLUSIONS: Patients less than 45 years of age, maxillary donor teeth, and an extraoral time of less than 15 minutes were associated with significantly higher tooth survival. Surgical extraction of the donor tooth was associated with a significantly higher incidence of IRR. Immediate transplantation after the extraction of the recipient site's tooth and low initial stability were associated with a significantly lower incidence of ankylosis. PMID- 26686825 TI - High risk of plant invasion in the understory of eucalypt plantations in South China. AB - Eucalypt plantations expand rapidly out of their natural distribution zones, thus inducing a concern on their effects on biodiversity and ecosystem functions. We compare the understory plant diversity of 46 plots of eucalypt plantations, including early and later stages in rotation, with that of 21 plots of contrast vegetation, including other types of plantations and secondary shrub grassland, in Guangdong and Guangxi Provinces, South China. Although the overall plant diversity did not change significantly in eucalypt plantations relative to the contrast vegetation, the community structures changed dramatically. The Asteraceae family, which is the most important source of destructive invasive plant species in China, is ranked 3(rd) (7.42%) and 7(th) (3.14%) in species importance in the early and later stages in eucalypt plantations, respectively. Nevertheless, Asteraceae is ranked 15(th) (1.73%) in other types of plantations and 21(st) (0.94%) in secondary shrub grassland. Significant increases in the richness and frequency of invasive species were also observed in eucalypt plantations. Among the 20 invasive species recorded in the eucalypt plantations, 9 species were destructive invasive species and 7 of these species belonged to Asteraceae. This study highlights an enhanced plant invasion risk in eucalypt plantations in South China, particularly by Asteraceae. PMID- 26686827 TI - Psychological resilience and intolerance of uncertainty in coping with cystic fibrosis. AB - BACKGROUND: Anxiety and depression are lower than to be expected in a considerable portion of cystic fibrosis (CF) patients. This outcome might be a result of substantial resilience and/or tolerance of uncertainty in coping with adversity. Research into resilience in cystic fibrosis is in its infancy. METHODS: 57 adult CF patients participated in the study during their routine medical checkup. In addition to regular psychological assessment, the Intolerance of Uncertainty Scale (IUS) and the Resilience Scale (RS) were administered. The relative importance of IUS and RS in predicting quality of life in CF was explored. Bivariate correlations and predictive value of variables in multiple regressions on subscales of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) were calculated. RESULTS: Remarkably, resilience (personal competence and acceptance) was clearly elevated, whereas intolerance of uncertainty was comparable to healthy reference groups. In multiple regressions, personal competence emerged as strongest resilience variable in the prediction of quality of life. CONCLUSIONS: CF patients in our study seem to be particularly resilient rather than cognitively avoidant. At this stage of research, fostering personal competence in CF patients is most promising in improving quality of life. PMID- 26686826 TI - Cefoxitin Plasma and Subcutaneous Adipose Tissue Concentration in Patients Undergoing Sleeve Gastrectomy. AB - PURPOSE: Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of this study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy. METHODS: A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of the surgical procedure, venous blood samples (5 mL) were collected just before cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition, subcutaneous adipose tissue was collected from the surgical site at the time of surgical incision and at closure. Cefoxitin concentrations in the collected samples were quantified by using an HPLC ultraviolet method. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration-time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. FINDINGS: Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. The mean age and BMI were 48.7 (6.2) years and 42.8 (7.1) kg/m(2), respectively. At the time of surgical closure, subcutaneous adipose tissue concentrations of cefoxitin were subtherapeutic (<8 ug/mL) in all evaluated patients. IMPLICATIONS: Current dosing strategies for cefoxitin in obese surgical patients may be inadequate, and there is an urgent need to define the appropriate dosage. PMID- 26686828 TI - A high throughput flow gradient LC-MS/MS method for simultaneous determination of fingolimod, fampridine and prednisone in rat plasma, application to in vivo perfusion study. AB - In this study a selective and high throughput liquid chromatography-mass spectrometry method was developed and validated for the simultaneous quantification of fingolimod (FLD), fampridine (FMP) and prednisone (PDN) in rat plasma using imipramine (IMP) as internal standard (ISTD). In this LC-MS method, following protein precipitation extraction (PPE), the analytes and ISTD were run on XBridge C18 column (150*4.6mm, 5MUm) using gradient mobile phase consisting of 5mM ammonium formate in water (pH 9.0) and acetonitrile in a flow gradience program. The drug precursor and product ions were monitored on a triple quadrupole instrument that was operated in positive ionization mode. The method was validated over a concentration range of 0.1-100ng/mL for all the three analytes with relative recoveries ranging from 69 to 82%. The intra and inter batch precision (% CV) across four validation runs were less than 13.4%. The accuracy determined at four QC levels (LLOQ, LQC, MQC and HQC) were within +/ 6.5% of CV values. The method proved to be highly reproducible and sensitive that was successfully applied in a pharmacokinetic study after single dose oral administration to the rats and also in perfusion study sample analysis. PMID- 26686829 TI - Development of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the determination of kinsenoside, an antihyperlipidemic candidate, in rat plasma and its application to pharmacokinetic studies. AB - Kinsenoside is a major bioactive constituent isolated from Anoectochilus formosanus and is investigated as an antihyperlipidemic candidate. In this study, a rapid, sensitive, and reliable bioanalytical method was developed for the determination of kinsenoside in rat plasma using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The plasma sample was pretreated with 1% acetic acid, followed by protein precipitation with acetonitrile:methanol (70:30). Chromatographic separation was performed on a HILIC silica column (2.1mm*100mm, 3MUm). The mobile phases consisted of 0.1% acetic acid in distilled water (solvent A) and 0.1% acetic acid in acetonitrile (solvent B). A gradient program was used at a flow rate of 0.2mL/min. For mass spectrometric detection, the multiple reaction monitoring mode was used; the MRM transitions were m/z 265.2->m/z 102.9 for kinsenoside and m/z 163.3->m/z 132.1 for the internal standard (IS) nicotine in the positive ionization mode. A calibration curve was constructed in the range of 2-500ng/mL. The intra- and interday precision and accuracy were within 5%. The HILIC-MS/MS method was specific, accurate, and reproducible and was successfully applied in a pharmacokinetic study of kinsenoside in rats. PMID- 26686830 TI - Advancement in integrin facilitated drug delivery. AB - The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. PMID- 26686831 TI - Recent developments in the Raman and infrared investigations of amorphous pharmaceuticals and protein formulations: A review. AB - The success rate for drug discovery and the development of innovative therapeutic strategies are intimately related to the physical properties of the solid-state condensed matter, which have direct influence on the bioavailability of Active Pharmaceutical Ingredients. In order to transform a new molecule in efficient drug, the material is brought into an amorphous state using various manufacturing processes including freeze drying, spray drying, hot melt extrusion and loading in different delivery devices. The infrared and Raman spectroscopic analyses used for exploring disordered and amorphous states, for the monitoring of the drug physical stability in drug delivery systems are described in this review. PMID- 26686833 TI - Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice. AB - Osteoarthritis (OA) is a progressive joint disorder which affects cartilage and subchondral bone. Calcitonin gene-related peptide (CGRP) plays a role in bone metabolism. The purpose of this study is to examine the therapeutic effect of the blocking CGRP on OA progression in mice by inhibition of subchondral bone sclerosis. OA was induced by the resection of the medial meniscotibial ligament of the knee in C57/BL6 mice. An intraperitoneal injection of the CGRP receptor antagonist (BIBN4096) was administered after OA surgery. At 1, 4, and 8 weeks after injection, histological analysis were performed. In vitro, the effect of CGRP and BIBN4096 on osteogenesis and osteoclastogenesis was analyzed. BIBN4096 could prevent cartilage degeneration and subchondral bone sclerosis. The OARSI score in the BIBN4096 group was significantly lower than that in the control. In vitro, CGRP up regulated osteocalcin expression, but its expression was down regulated by BIBN4096. CGRP inhibited osteoclastogenesis of raw 267.4 cells, but its effect was reduced by the addition of BIBN4096.The current study showed that subchondral bone sclerosis and increasing expression of CGRP occurs in the early phase of OA in relation to cartilage degeneration, and that BIBN4096 could effectively attenuate OA progression. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1177-1184, 2016. PMID- 26686834 TI - Regulation of BmBDV NS1 by phosphorylation: Impact of mutagenesis at consensus phosphorylation sites on ATPase activity and cytopathic effects. AB - Bombyx mori bidensovirus (BmBDV) is a single-stranded DNA virus belonging to the Bidensovirus genus, Bidnaviridae family. Previous studies showed that parvovirus nonstructural protein 1 (NS1) contains endonuclease, helicase, and ATPase activities and that these activities are regulated by serine/threonine phosphorylation. We have reported that residue Thr-184 site of BmBDV NS1 is phosphorylated, and that residues of Thr-181 and Thr-191 are potentially phosphorylated. However, whether phosphorylation affects BmBDV NS1 activities remains unclear. In this study, the substitution of threonine with Glycine at positions 181, 184 and 191 of BmBDV NS1 reduced its ATPase activity. After wild type NS1 was treated with calf intestinal alkaline phosphatase (CIP), ATPase activity decreased significantly. Moreover, silkworms that were injected with recombinant viruses carrying these NS1 mutations exhibited significant increases in the median lethal time to death compared with silkworms that were injected with a virus that expressed wild-type NS1. In conclusion, these results showed that the ATPase activity and virulence of BmBDV NS1 are regulated via phosphorylation. PMID- 26686832 TI - Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines. AB - Small interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bioconjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. However, most cases address local applications or diseases in the filtering organs, reflecting remaining challenges in systemic delivery of siRNA. The difficulty in siRNA delivery is in large part due to poor circulation stability and unfavorable pharmacokinetics and biodistribution profiles of siRNA. This review describes the pharmacokinetics and biodistribution of siRNA nanomedicines, focusing on those reported in the past 5years, and their pharmacological effects in selected disease models such as hepatocellular carcinoma, liver infections, and respiratory diseases. The examples discussed here will provide an insight into the current status of the art and unmet needs in siRNA delivery. PMID- 26686835 TI - Allowing time to consolidate knowledge gained through random practice facilitates later novel motor sequence acquisition. AB - Two experiments were conducted to examine the efficacy of random (RP) and blocked practice (BP) for enhancing later motor learning. Each experiment involved practicing three unique seven key serial reaction time (SRT) tasks in either a blocked or random format followed by practice of a novel SRT task either 2-min (Experiment 1) or 24-h (Experiment 2) later. While the expected benefit of RP for retention was present in both experiments, in Experiment 1 there was no advantage from prior RP for new learning. Experiment 2 explored the possibility that increasing the interval, from 2-min to 24-h, between BP or RP and practice of the novel motor task might allow consolidation of sequence knowledge acquired during BP or RP which in turn might facilitate new learning. As a result of the additional time between training bouts RP facilitated the rate at which the novel motor task was acquired. Interestingly, when this additional time was provided, both BP and RP supported (a) a performance saving for the first trial with the novel task, and (b) an offline improvement in performance across a 24-h interval not present when only the novel motor task was practiced. The latter benefits for new learning may have resulted from exposure to prior physical practice per se. or practice variability. These data are discussed with respect to (a) future learning benefits from prior experience training with greater CI, and (b) the importance of memory consolidation for motor learning. PMID- 26686836 TI - Argonaute3 is a key player in miRNA-mediated target cleavage and translational repression in Chlamydomonas. AB - MicroRNAs (miRNAs) play important roles in diverse biological processes in eukaryotes, generally through degradation and/or inhibition of the translation of target mRNAs. MicroRNAs are loaded into Argonaute (AGO) proteins to form the RNA induced silencing complex (RISC) and used as guides to identify complementary transcripts. The distinct functions and features, such as associated small RNA classes and modes of silencing, of individual AGO paralogs have been well documented in multicellular eukaryotes. However, this aspect of miRNA function remains poorly understood in the unicellular green alga Chlamydomonas reinhardtii, which contains three AGO paralogs. In this study, we isolated AGO2 and AGO3 insertional mutants and confirmed that AGO3 is more abundantly expressed than AGO2. MicroRNA-directed target transcript cleavage and translational repression were impaired in the AGO3 mutant background, indicating that AGO3 can mediate both modes of silencing. In contrast, although the AGO2 mutant is not a null, the involvement of AGO2 in miRNA-directed silencing appears to be more limited. Our results strongly suggest that miRNA-mediated post-transcriptional gene silencing relies primarily on AGO3 in Chlamydomonas. PMID- 26686837 TI - Early detection of Alzheimer's disease using MRI hippocampal texture. AB - Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently applied to score independent data sets from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and the Metropolit 1953 Danish Male Birth Cohort (Metropolit). Hippocampal texture was superior to volume reduction as predictor of MCI-to-AD conversion in ADNI (area under the receiver operating characteristic curve [AUC] 0.74 vs. 0.67; DeLong test, p = 0.005), and provided even better prognostic results in AIBL (AUC 0.83). Hippocampal texture, but not volume, correlated with Addenbrooke's cognitive examination score (Pearson correlation, r = -0.25, p < 0.001) in the Metropolit cohort. The hippocampal texture marker correlated with hippocampal glucose metabolism as indicated by fluorodeoxyglucose-positron emission tomography (Pearson correlation, r = -0.57, p < 0.001). Texture statistics remained significant after adjustment for volume in all cases, and the combination of texture and volume did not improve diagnostic or prognostic AUCs significantly. Our study highlights the presence of hippocampal texture abnormalities in MCI, and the possibility that texture may serve as a prognostic neuroimaging biomarker of early cognitive impairment. PMID- 26686838 TI - Preterm delivery and risk for early language delays: a sibling-control cohort study. AB - BACKGROUND: Studies suggest that preterm delivery is a risk factor for early language delays, but knowledge is scarce about the persistence of the delays and whether the association is of a linear kind. To resolve this, effects of confounding risk factors that are both shared within a family and pregnancy specific need to be distinguished from effects of preterm delivery. Our study examines the association between early gestational age and language outcomes, using a sibling-control design. METHODS: The sample comprises 22,499 siblings from the Norwegian Mother and Child Birth Cohort Study, recruited between 1999 and 2008. Mothers rated child language comprehension and production at 18 and 36 months. Analyses compared siblings discordant on gestational age group (early preterm, delivery at week 22-33; late preterm, 34-36; early term, 37-38; full term, >38) and type of onset of delivery (spontaneous; provider-initiated), and compared these findings with conventional cohort analyses. RESULTS: The findings revealed inverse linear relations between the gestational age groups, and persistent but diminishing language delays. Effects of preterm delivery were substantial on both language production and comprehension at 18 months. By 36 months, the effects of preterm delivery were weaker, but still extensive, in particular for language production in provider-initiated births. When comparing sibling-control with cohort analyses, preterm group was less important among spontaneous births, but remained important in provider-initiated births. Familial and pregnancy risk factors partly explained this. CONCLUSIONS: Distinctive factors seem to underlie effects of preterm delivery across spontaneous and provider-initiated births. PMID- 26686839 TI - Cohort Profile: Community-based prospective cohort from the National Cancer Center, Korea. PMID- 26686840 TI - Cohort Profile: The MD Anderson Cancer Patients and Survivors Cohort (MDA-CPSC). PMID- 26686841 TI - Cohort Profile: The PREDICT Cardiovascular Disease Cohort in New Zealand Primary Care (PREDICT-CVD 19). PMID- 26686842 TI - Probabilistic record linkage. AB - Studies involving the use of probabilistic record linkage are becoming increasingly common. However, the methods underpinning probabilistic record linkage are not widely taught or understood, and therefore these studies can appear to be a 'black box' research tool. In this article, we aim to describe the process of probabilistic record linkage through a simple exemplar. We first introduce the concept of deterministic linkage and contrast this with probabilistic linkage. We illustrate each step of the process using a simple exemplar and describe the data structure required to perform a probabilistic linkage. We describe the process of calculating and interpreting matched weights and how to convert matched weights into posterior probabilities of a match using Bayes theorem. We conclude this article with a brief discussion of some of the computational demands of record linkage, how you might assess the quality of your linkage algorithm, and how epidemiologists can maximize the value of their record linked research using robust record linkage methods. PMID- 26686843 TI - Aerobic fitness in late adolescence and the risk of early death: a prospective cohort study of 1.3 million Swedish men. AB - BACKGROUND: Fitness level and obesity have been associated with death in older populations. We investigated the relationship between aerobic fitness in late adolescence and early death, and whether a high fitness level can compensate the risk of being obese. METHODS: The cohort comprised 1 317 713 Swedish men (mean age, 18 years) that conscripted between 1969 and 1996. Aerobic fitness was assessed by an electrically braked cycle test. All-cause and specific causes of death were tracked using national registers. Multivariable adjusted associations were tested using Cox regression models. RESULTS: During a mean follow-up period of 29 years, 44 301 subjects died. Individuals in the highest fifth of aerobic fitness were at lower risk of death from any cause [hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.47-0.51] in comparison with individuals in the lowest fifth, with the strongest association seen for death related to alcohol and narcotics abuse (HR, 0.20; 95% CI, 0.15-0.26). Similar risks were found for weight-adjusted aerobic fitness. Aerobic fitness was associated with a reduced risk of death from any cause in normal-weight and overweight individuals, whereas the benefits were reduced in obese individuals (P < 0.001 for interaction). Furthermore, unfit normal-weight individuals had 30% lower risk of death from any cause (HR, 0.70; 95% CI, 0.53-0.92) than did fit obese individuals. CONCLUSIONS: Low aerobic fitness in late adolescence is associated with an increased risk of early death. Furthermore, the risk of early death was higher in fit obese individuals than in unfit normal-weight individuals. PMID- 26686844 TI - Sprengel anomaly in deletion 22q11.2 (DiGeorge/Velo-Cardio-Facial) syndrome. AB - Sprengel anomaly (SA) is a rare skeletal defect characterized by uni- or bi lateral elevation of the scapula. This anomaly is often isolated, although it can occur in association with other defects, including cervical spine malformations, cleft palate, and facial anomalies. Neural crest migration anomalies have been involved in the etiology of SA. Since the same embryological pathway accounts for some of the clinical features of deletion 22q11.2 syndrome (del22q11.2; DiGeorge/Velo-Cardio-Facial syndrome), we investigated the occurrence of SA in a consecutive series of 235 del22q11.2 patients aged more than 2 years, undergoing a complete clinical and orthopedic assessment of the dorsal and thoracic skeleton. In the present series, two patients were diagnosed with true SA. Present results and published reports suggest that scapular involvement including SA occurs in 1-2% of del22q11.2 individuals. Accordingly, this anomaly should be investigated as one of the possible skeletal findings of del22q11.2 syndrome, while this diagnosis should be excluded in patients presenting with SA associated with other defects. PMID- 26686845 TI - Is It Safe to Operate on Patients Taking Isotretinoin? AB - BACKGROUND: Oral isotretinoin is increasingly being used to treat acne and other dermatological conditions. The number of patients who take isotretinoin and wish or need to undergo plastic surgery may be following a similar pattern. Although skin healing is an important concern in the case of patients who use isotretinoin, it is definitely not the only relevant issue when planning surgical intervention. METHODS: Eleven important points regarding surgery safety in patients taking oral isotretinoin were defined. A literature search of the PubMed database was conducted by employing the keywords isotretinoin OR 13-cis-retinoic acid. This returned the largest possible number of studies about isotretinoin. RESULTS: Forty-seven studies matched the selection criteria. Most animal experimental models suggested that isotretinoin at doses commonly used to treat acne is not detrimental to wound healing. Human studies are controversial. However, healing of skeletal muscle could be at increased risk of necrosis. CONCLUSIONS: Association between isotretinoin and problematic skin healing after surgery is being challenged. Also, recommended time between discontinuation of isotretinoin and surgery should be reviewed. While muscle flaps may be endangered in patients taking isotretinoin, healing of other tissues and systemic effects that could compromise surgery safety are rare or detectable before surgery. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26686846 TI - Calcium Fructoborate for Bone and Cardiovascular Health. AB - Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex "protective" effect against inflammatory response. CF is commercially available in the USA as a "nature identical" complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C reactive protein (CRP). PMID- 26686847 TI - Effect of Selenium Supplementation on Glycemic Control and Lipid Profiles in Patients with Diabetic Nephropathy. AB - To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 MUg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles. PMID- 26686849 TI - New insights into childhood leukemia etiology. PMID- 26686848 TI - Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian patients. AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA. PMID- 26686850 TI - Progress and challenges in implementing HIV care and treatment policies in Latin America following the treatment 2.0 initiative. AB - BACKGROUND: The Pan American Health Organization provides technical cooperation to countries in Latin America and the Caribbean for the scale-up of HIV care and treatment based on the Treatment 2.0 initiative. Fourteen Joint Review Missions (JRMs) were conducted between March 2012 and October 2014. Evaluating the degree of implementation of the recommendations of the JRMs and their impact on health policies, would help countries identify their gaps and areas for priority interventions. METHODS: A descriptive analysis of the JRM recommendations was conducted for eight countries. An in-depth cross-sectional retrospective analysis of the degree of implementation of these recommendations in Ecuador, Venezuela, Bolivia, and El Salvador was performed through a standardized self-administered questionnaire applied to key informants. A comparative quantitative analysis on the optimization of antiretroviral regimens 'before/after' JRMs was conducted in three of the latter four countries, using data reported in 2013 and 2014. RESULTS: The priority areas with most recommendations were the optimization of antiretroviral treatment (ART) regimens (n = 57), the rational and efficient use of resources (n = 27) and the provision of point-of-care diagnostics and monitoring tools (n = 26), followed by community mobilization (n = 23), strategic information (n = 17) and the adaptation of delivery services (n = 15). The in depth analysis in four countries showed that the two priority areas where most progress was observed were the rational and efficient use of resources (62%) and the optimization of ART regimens (60%). Adaptation of delivery services, community mobilization and strategic information were rated at 52% and the provision of point-of-care diagnostics and monitoring tools 38%. The quantitative analysis on optimization evidenced a 36% reduction in the number of first-line and second-line ART regimens, a 5.4% increase in the proportion of patients on WHO-recommended first-line regimens, a 19.4% increase in the use of the WHO preferred first-line regimen, 51% increase in the use of WHO-recommended second line regimens, and a significant reduction in the use of obsolete drugs in first- and second-line regimens (respectively 1 and 9% of regimens in 2013). CONCLUSIONS: A relatively good level of progress was perceived in the recommendations related to optimization of ART regimens. Challenges remain on the improvement of recommendations related to health system strengthening and the promotion and support aimed at community-based organizations as part of the response to HIV/AIDS in Latin America. The JRMs are a useful mechanism for providing coherent technical support to guide countries in the pursuit of a comprehensive response to HIV/AIDS in the Latin American region. PMID- 26686851 TI - Associations of body mass index and gestational weight gain with term pregnancy outcomes in urban Cameroon: a retrospective cohort study in a tertiary hospital. AB - BACKGROUND: Obesity is a rising public health issue worldwide. Guidelines regarding maternal body mass index (BMI) and gestational weight gain (GWG) are missing in Cameroon where maternal mortality rate remains very high. We hypothesized that obesity and inappropriate GWG are associated with poor pregnancy outcomes. We aimed at assessing associations of BMI and GWG with pregnancy outcomes. METHODS: This was a retrospective cohort study at the Yaounde Central Hospital. We included women with term singleton deliveries in the post partum ward. The World Health Organisation classification of BMI and the United States Institute Of Medicine (IOM) categories of GWG were used to stratify participants. Poor maternal outcome was defined by the occurence of caesarean section, preeclampsia or obstetrical haemorrhage. Poor perinatal outcome was defined by the occurence of perinatal death, admission in intensive care unit, low birth weight, macrosomia or fifth minute Apgar score <7. Multiple logistic regressions were used to calculate unadjusted and adjusted Odds Ratios (uOR, aOR) for poor maternal outcome (PMO) and for poor perinatal outcome (PPO) in each category of BMI and GWG. Adjustment was done for age, scarred uterus, sickle cell disease, malaria, human immunodeficiency virus (HIV) infection, parity and smoking. RESULTS: Of the 462 participants, 17 (4 %) were underweight (BMI < 18.5), 228 (49 %) had normal pre-pregnancy BMI, 152 (33 %) were overweight (25 <= BMI < 30) and 65 (14 %) were obese (BMI >= 30). Following the IOM recommendations, GWG was normal for 186 (40 %) participants, less than recommended for 131 (28 %) and above the recommended norms for 145 (32 %). GWG above the IOM recommendation was significantly associated with PMO (aOR: 1.7, 95 % CI 1.1-2.8). GWG less than the IOM recommended values, overweight and obesity were not significantly associated with poor pregnancy outcomes. CONCLUSION: While waiting for local recommendations for GWG, the IOM recommendations can be used for Cameroonian women as far as maternal outcome is concerned. Unlike in studies in different ethnic and racial groups, abnormal BMI was not associated with poor pregnancy outcomes in our cohort of Cameroonian women. PMID- 26686852 TI - Computer navigation versus fluoroscopy-guided navigation for thoracic pedicle screw placement: a meta-analysis. AB - Although application of intraoperative computer navigation technique had been integrated into placement of pedicle screws (PSs) in thoracic fusion for years, its security and practicability remain controversial. The aim of this study is to evaluate the accuracy, the operative time consumption, the amount of intraoperative blood loss, time of pedicle insertion and the incidence of complications of thoracic pedicle screw placement in patients with thoracic diseases such as scoliosis and kyphosis. Pubmed, Web of Knowledge, and Google scholar were searched to identify comparative studies of thoracic pedicle screw placement between intraoperative computer navigation and fluoroscopy-guided navigation. Outcomes of malposition rate, operative time consumption, insertion time, intraoperative blood loss, and the incidence of complications are evaluated. Fourteen articles including 1723 patients and 9019 PSs were identified matching inclusion criteria. The malposition rate was lower (RR: 0.33, 95 % CI: 0.28-0.38, P < 0.01) in computer navigation group than that in fluoroscopy-guided navigation group; the operative time was significantly longer [weighted mean difference (WMD) = 23.66, 95 % CI: 14.74-32.57, P < 0.01] in computer navigation group than that in fluoroscopy-guided navigation group. The time of insertion was shorter (WMD = -1.88, 95 % CI: -2.25- -1.52, P < 0.01) in computer navigation group than that in fluoroscopy-guided navigation group. The incidence of complications was lower (RR = 0. 23, 95 % CI: 0.12-0.46, P < 0.01) in computer navigation group than that in the other group. The intraoperative blood loss was fewer (WMD = -167.49, 95 % CI: -266.39- -68.58, P < 0.01) in computer navigation group than that in the other. In conclusion, the meta-analysis of thoracic pedicle screw placement studies clearly demonstrated lower malposition rate, less intraoperative blood loss, and fewer complications when using computer navigation. This result provides strong evidence that computer technology could be safer and more reliable than fluoroscopy-guided navigation. PMID- 26686853 TI - Compliance with recommendations on surgery for primary hyperparathyroidism-from guidelines to real practice: results from an Iberian survey. AB - PURPOSE: Knowledge about compliance with recommendations derived from the positional statement of the European Society of Endocrine Surgeons on modern techniques in primary hyperparathyroidism surgery and the Third International Workshop on management of asymptomatic primary hyperparathyroidism is scarce. Our purpose was to check it on a bi-national basis and determine whether management differences may have impact on surgical outcomes. METHODS: An online survey including questions about indications, preoperative workup, surgical approach, intraoperative adjuncts, and outcomes was sent to institutions affiliated to the endocrine surgery divisions of the National Surgical Societies from Spain and Portugal. A descriptive evaluation of the responses was performed. Finally, we assessed the correlation between the different types of management with the achievement of optimal results, defined as a cure rate equal or greater than the median of all interviewed institutions. RESULTS: Fifty-seven hospitals (41 Spanish, 16 Portuguese) answered the survey. First-ordered imaging tests were neck ultrasound and sestamibi scan. Facing negative or non-concordant results, 44 % of surgeons ordered additional tests before first-time surgery, and 84 % before reoperations. When indicated, selective parathyroidectomy was an acceptable option for 95 % of institutions as first-time surgery and for 51 % in reoperations. Intraoperative parathormone measurements were used by 92 % of departments. The surgical outcomes were good in most institutions (median cure rate 97 %) and were influenced mostly by the presence of an endocrine surgery unit in the surgical department (p = 0.038). CONCLUSIONS: Practice of Iberian endocrine surgeons is consistent with current recommendations on surgery for primary hyperparathyroidism, with variability in some areas. PMID- 26686854 TI - Assessing toxic effects of [Omim]Cl and [Omim]BF4 in zebrafish adults using a biomarker approach. AB - In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl) and 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF4) on the zebrafish livers were studied at 0, 5, 10, 20, and 40 mg L(-1) on the 7th and 14th days. In addition, the concentrations of [Omim]Cl and [Omim]BF4 in the test water, the acute toxicity of the two ionic liquids (ILs), and the influence of anions on the toxicity of the ILs were evaluated. The acute toxicity test results showed 50 % lethal concentration (LC50) values of 152.3 +/- 12.1 mg L(-1) for [Omim]Cl and 144.0 +/- 11.4 mg L(-1) for [Omim]BF4. At the lowest concentration investigated (5 mg L(-1)), [Omim]Cl and [Omim]BF4 did not significantly affect zebrafish during the exposure period. However, the toxic effects of these substances were enhanced as dosing concentrations and exposure times were increased. Levels of reactive oxygen species (ROS) were significantly enhanced on the 7th day after 20 mg L(-1) and on the 14th day after 10 mg L(-1) of either substance was applied, resulting in oxidative damage, such as lipid peroxidation and DNA damage. The experimental results also indicated little effect of the anions on the toxicity of ILs and consistent toxic effects of [Omim]Cl and [Omim]BF4. Graphical Abstract The graphical abstract for the present study after exposure to [Omim]Cl and [Omim]BF4. The letter R represents the anions Cl(-) and BF4 (.) PMID- 26686855 TI - Mercury, lead, and cadmium in tissues of the Caspian Pond Turtle (Mauremys caspica) from the southern basin of Caspian Sea. AB - Concentrations of cadmium, lead, and mercury were measured in different tissues (liver, muscle, and shell) of 60 Caspian Pond Turtles collected from Tajan and Shiroud Rivers, southern basin of the Caspian Sea. Based on the results, different tissues showed different capacities for accumulating trace elements. The general trend of metals accumulation was: liver > shell > muscle. Results also showed that accumulation of these elements was not significantly different between sex and river in turtles (p > 0.05). Based on the results, Hg and Pb concentrations recorded in the present study were higher than some of the maximum concentration permissible. To our knowledge, this is the first report into heavy metal accumulation in tissues and organs of Caspian Pond Turtle from the southern basin of Caspian Sea. Further studies are needed to measure different heavy metals and trace metals in this valuable species. PMID- 26686857 TI - An overview of groundwater chemistry studies in Malaysia. AB - In this paper, numerous studies on groundwater in Malaysia were reviewed with the aim of evaluating past trends and the current status for discerning the sustainability of the water resources in the country. It was found that most of the previous groundwater studies (44 %) focused on the islands and mostly concentrated on qualitative assessment with more emphasis being placed on seawater intrusion studies. This was then followed by inland-based studies, with Selangor state leading the studies which reflected the current water challenges facing the state. From a methodological perspective, geophysics, graphical methods, and statistical analysis are the dominant techniques (38, 25, and 25 %) respectively. The geophysical methods especially the 2D resistivity method cut across many subjects such as seawater intrusion studies, quantitative assessment, and hydraulic parameters estimation. The statistical techniques used include multivariate statistical analysis techniques and ANOVA among others, most of which are quality related studies using major ions, in situ parameters, and heavy metals. Conversely, numerical techniques like MODFLOW were somewhat less admired which is likely due to their complexity in nature and high data demand. This work will facilitate researchers in identifying the specific areas which need improvement and focus, while, at the same time, provide policymakers and managers with an executive summary and knowledge of the current situation in groundwater studies and where more work needs to be done for sustainable development. PMID- 26686856 TI - Unexpected effects of sublethal doses of insecticide on the peripheral olfactory response and sexual behavior in a pest insect. AB - Pesticides have long been used as the main solution to limit agricultural pests, but their widespread use resulted in chronic or diffuse environmental pollutions, development of insect resistances, and biodiversity reduction. The effects of low residual doses of these chemical products on organisms that affect both targeted species (crop pests) but also beneficial insects became a major concern, particularly because low doses of pesticides can induce unexpected positive--also called hermetic--effects on insects, leading to surges in pest population growth at greater rate than what would have been observed without pesticide application. The present study aimed to examine the effects of sublethal doses of deltamethrin, one of the most used synthetic pyrethroids, known to present a residual activity and persistence in the environment, on the peripheral olfactory system and sexual behavior of a major pest insect, the cotton leafworm Spodoptera littoralis. We highlighted here a hormetic effect of sublethal dose of deltamethrin on the male responses to sex pheromone, without any modification of their response to host-plant odorants. We also identified several antennal actors potentially involved in this hormetic effect and in the antennal detoxification or antennal stress response of/to deltamethrin exposure. PMID- 26686858 TI - Central nervous system involvement by Waldenstrom macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. AB - Bing-Neel syndrome (BNS) is a rare complication seen in patients with Waldenstrom macroglobulinaemia (WM), in which lymphoplasmacytic lymphoma cells colonize the central nervous system. In this retrospective multi-centre study, we present the clinicopathological features, imaging findings, therapy, response and outcomes of 34 patients with BNS. The median time from WM diagnosis to BNS diagnosis was 3 years, 15% of patients were diagnosed with BNS at the time of WM diagnosis, and 22% of patients developed BNS when responding to active treatment for WM. Patients with BNS presented with variable clinical features including limb motor deficits, change in mental status and cranial nerve palsies. The diagnosis was made using a combination of cerebrospinal fluid cytology, flow cytometry and detection of the MYD88 L265 mutation, and magnetic resonance imaging. The estimated 3-year overall survival rate was 59%. Of the survivors, 40% have evidence of pathological and/or radiological persistence of disease. Age older than 65 years, platelet count lower than 100 * 10(9) /l, and treatment for WM prior to BNS diagnosis were associated with worse outcome. Exposure to rituximab for treatment of BNS was associated with a better outcome. Multi-institutional collaboration is warranted to improve treatment and outcomes in patients with BNS. PMID- 26686859 TI - National Cancer Institute-supported chemotherapy-induced peripheral neuropathy trials: outcomes and lessons. AB - Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional--yet unsubstantiated--practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity. PMID- 26686860 TI - The role of 12/15-lipoxygenase in production of selected eicosanoids in allergic airway inflammation. AB - PURPOSE: To evaluate the role of 12/15-lipoxygenase (LOX) in regulation of synthesis of selected eicosanoids in mice sensitized and challenged with Dermatophagoides pteronyssinus (Dp) allergen extract. MATERIALS AND METHODS: Both C57Bl and 12/15-LOX knockout mice were sensitized by 2 intraperitoneal injections and subsequently challenged by inhalation with Dp allergen extract. Sham sensitized and challenged mice were used as controls. Samples of bronchoalveolar lavage (BAL) were used for assessment of prostaglandin E2 (PGE2), cysteinyl leukotreienes (cysLT), lipoxin A4 (LXA4) and 15-hydroxyeicosatetraenoic acid (15 HETE) concentration using ELISA method. Whole lung samples were used for isolation of RNA and evaluation of selected genes involved in eicosanoid metabolism, including cyclooxygenase-2 (COX-2), 12/15-LOX, 5-LOX and 5-LOX activated protein (FLAP). RESULTS: Allergen-induced airway inflammation was associated with significant (9-fold, 95% CI 8.068-9.932-fold; p<0.05) up regulation of 12/15-LOX in wild type but not in the 12/15-LOX knockout mice in which 12/15-LOX mRNA remained undetectable. Lack of 12/15-LOX was associated with significant attenuation of production of 15-HETE in response to allergen challenge. On the contrary, the greatest up-regulation of COX-2 after allergen exposure was demonstrated in the 12/15-LOX knockout mice (4.3-fold vs sham group) and was significantly greater than in the wild type counterparts (5.185-fold, 95% CI 4.723-6.309-fold; p<0.05 vs wild type mice). Also, allergen challenged 12/15 LOX knockout mice were characterized by greater production of PGE2 and cysLT. CONCLUSION: The 12/15-LOX plays an important role in the metabolism of eicosanoids in response to allergen-induced airway inflammation. PMID- 26686863 TI - Recombinant protein blends: silk beyond natural design. AB - Recombinant DNA technology and new material concepts are shaping future directions in biomaterial science for the design and production of the next generation biomaterial platforms. Aside from conventionally used synthetic polymers, numerous natural biopolymers (e.g., silk, elastin, collagen, gelatin, alginate, cellulose, keratin, chitin, polyhydroxyalkanoates) have been investigated for properties and manipulation via bioengineering. Genetic engineering provides a path to increase structural and functional complexity of these biopolymers, and thereby expand the catalog of available biomaterials beyond that which exists in nature. In addition, the integration of experimental approaches with computational modeling to analyze sequence-structure-function relationships is starting to have an impact in the field by establishing predictive frameworks for determining material properties. Herein, we review advances in recombinant DNA-mediated protein production and functionalization approaches, with a focus on hybrids or combinations of proteins; recombinant protein blends or 'recombinamers'. We highlight the potential biomedical applications of fibrous protein recombinamers, such as Silk-Elastin Like Polypeptides (SELPs) and Silk-Bacterial Collagens (SBCs). We also discuss the possibility for the rationale design of fibrous proteins to build smart, stimuli responsive biomaterials for diverse applications. We underline current limitations with production systems for these proteins and discuss the main trends in systems/synthetic biology that may improve recombinant fibrous protein design and production. PMID- 26686861 TI - FOXO transcription factors in cancer development and therapy. AB - The forkhead box O (FOXO) transcription factors are considered as tumor suppressors that limit cell proliferation and induce apoptosis. FOXO gene alterations have been described in a limited number of human cancers, such as rhabdomyosarcoma, leukemia and lymphoma. In addition, FOXO proteins are inactivated by major oncogenic signals such as the phosphatidylinositol-3 kinase pathway and MAP kinases. Their expression is also repressed by micro-RNAs in multiple cancer types. FOXOs are mediators of the tumor response to various therapies. However, paradoxical roles of FOXOs in cancer progression were recently described. FOXOs contribute to the maintenance of leukemia-initiating cells in acute and chronic myeloid leukemia. These factors may also promote invasion and metastasis of subsets of colon and breast cancers. Resistance to treatment was also ascribed to FOXO activation in multiple cases, including targeted therapies. In this review, we discuss the complex role of FOXOs in cancer development and response to therapy. PMID- 26686862 TI - TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization. AB - The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Abeta, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID- 26686864 TI - Dietary Administration of Lactobacillus plantarum Enhanced Growth Performance and Innate Immune Response of Siberian Sturgeon, Acipenser baerii. AB - We investigated the effects of Lactobacillus plantarum used as a dietary supplement on the growth performance and innate immune response in juvenile Siberian sturgeon Acipenser baerii. Juvenile fish (14.6 +/- 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 * 10(7), 1 * 10(8) and 1 * 10(9) colony-forming units (cfu) g(-1)] and a control (non-supplemented basal) diet for 8 weeks. Growth performance indices were increased in fish fed the 1 * 10(8) cfu g(-1) L. plantarum diet compared to the other groups. There was an increased innate immune response in fish fed the experimental diets. The highest levels of lysozyme activity, total immunoglobulin (IgM) and complement component 3 (C3) were observed in fish fed the diet containing L. plantarum at a concentration of 1 * 10(8) cfu g(-1), but there was no significant difference in the level of complement component 4 (C4) in fish fed the experimental diets or the control diet. The present study underlying some positive effects (growth performance and immune indices) of dietary administration of L. plantarum at a concentration of 1 * 10(8) cfu g(-1) in the Siberian sturgeon. PMID- 26686865 TI - From margarine to butter: predictors of changing bread spread in an 11-year population follow-up. AB - OBJECTIVE: Finland is known for a sharp decrease in the intake of saturated fat and cardiovascular mortality. Since 2000, however, the consumption of butter containing spreads - an important source of saturated fats - has increased. We examined social and health-related predictors of the increase among Finnish men and women. DESIGN: An 11-year population follow-up. SETTING: A representative random sample of adult Finns, invited to a health survey in 2000. SUBJECTS: Altogether 5414 persons aged 30-64 years at baseline in 2000 were re-invited in 2011. Of men 1529 (59 %) and of women 1853 (66 %) answered the questions on bread spreads at both time points. Respondents reported the use of bread spreads by choosing one of the following alternatives: no fat, soft margarine, butter vegetable oil mixture and butter, which were later categorized into margarine/no spread and butter/butter-vegetable oil mixture (= butter). The predictors included gender, age, marital status, education, employment status, place of residence, health behaviours, BMI and health. Multinomial regression models were fitted. RESULTS: Of the 2582 baseline margarine/no spread users, 24.6% shifted to butter. Only a few of the baseline sociodemographic or health-related determinants predicted the change. Finnish women were more likely to change to butter than men. Living with a spouse predicted the change among men. CONCLUSIONS: The change from margarine to butter between 2000 and 2011 seemed not to be a matter of compliance with official nutrition recommendations. Further longitudinal studies on social, behavioural and motivational predictors of dietary changes are needed. PMID- 26686866 TI - Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. AB - Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding. PMID- 26686867 TI - Impact of advanced monitoring variables on intraoperative clinical decision making: an international survey. AB - To assess the relationship between the addition of advanced monitoring variables and changes in clinical decision-making. A 15-questions survey was anonymously emailed to international experts and physician members of five anesthesia societies which focused on assessing treatment decisions of clinicians during three realistic clinical scenarios measured at two distinct time points. The first is when typical case information and basic monitoring (T1) were provided, and then once again after the addition of advanced monitoring variables (T2). We hypothesized that the addition of advanced variables would increase the incidence of an optimal therapeutic decision (a priori defined as the answer with the highest percentage of expert agreement) and decrease the variability among the physician's suggested treatments. The survey was completed by 18 experts and 839 physicians. Overall, adding advanced monitoring did not significantly increase physician response accuracy, with the least substantial changes noted on questions related to volume expansion or vasopressor administration. Moreover, advanced monitoring data did not significantly decrease the high level of initial practice variability in physician suggested treatments (P = 0.13), in contrast to the low variability observed within the expert group (P = 0.039). Additionally, 5 10 years of practice (P < 0.0001) and a cardiovascular subspecialty (P = 0.048) were both physician characteristics associated with a higher rate of optimal therapeutic decisions. The addition of advanced variables was of limited benefit for most physicians, further indicating the need for more in depth education on the clinical value and technical understanding of such variables. PMID- 26686868 TI - The effect of aloe emodin-encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells. AB - Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)-encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm(2) ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human gastric cancer cells. PMID- 26686869 TI - Can intravoxel incoherent motion diffusion-weighted imaging characterize the cellular injury and microcirculation alteration in hepatic ischemia-reperfusion injury? An animal study. AB - PURPOSE: To investigate whether intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can be used to quantitatively analyze the cellular injury and microcirculation alterations in hepatic ischemia-reperfusion injury (HIRI). MATERIALS AND METHODS: Thirty-two New Zealand white rabbits were randomly and equally assigned to the sham group, 1-hour, 4-hour, and 12-hour groups according to the reperfusion time after 1 hour of ischemia using a 70% liver ischemia reperfusion injury model. All the animals underwent IVIM-DWI with 12 b values at 1.5T. The imaging parameters (IVIM parameters and apparent diffusion coefficient [ADC]) among different groups were compared. The correlations between imaging parameters and histological scores, and the ratio of serum aspartate aminotransferase to serum alanine aminotransferase (serum AST/ALT) were analyzed. RESULTS: During the first hour of HIRI, true diffusion coefficient (D) and ADC significantly decreased (P < 0.05), while there was no significant decrease in perfusion fraction (f) (P = 0.708). There was fair to good correlation between histological scores and f (rs = -0.493 with the sham cases excluded, and -0.682 with all cases, both P < 0.05) and ADC (rs = -0.479 with the sham cases excluded, and -0.766 with all cases, both P < 0.05). There was no correlation between imaging parameters and serum AST/ALT with the sham cases excluded (P = 0.673 for f, 0.568 for D, 0.403 for ADC), and good correlation between D, ADC, and serum AST/ALT (r = 0.747 and 0.748, both P < 0.001) with all cases. CONCLUSION: IVIM-DWI can quantitatively characterize an animal model of HIRI, with D and ADC sensitive in early detection of cellular injury, as well as fair to good correlation between f, ADC, and microcirculation alteration. J. Magn. Reson. Imaging 2016;43:1327-1336. PMID- 26686870 TI - ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias. PMID- 26686871 TI - Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies. AB - PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non responders are truly biologically non-responsive or actually non-adherent? Therefore, the aim of this study was to describe, within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), characteristics of both non responders and high responders of statin treatment in order to possibly discriminate non-responders from non-adherers. METHODS: Baseline characteristics of non-responders to statin therapy (<=10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non-responders from the analysis. RESULTS: Non responders to statin therapy were younger (p = 0.001), more often smoked (p < 0.001), had a higher alcohol consumption (p < 0.001), had lower LDL cholesterol levels (p < 0.001), had a lower prevalence of hypertension (p < 0.001), and had lower cognitive function (p = 0.035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased. CONCLUSION: Our results suggest that non-responders to statin therapy are more likely to actually be non-adherers, since they have more characteristics that are viewed as indicators of high self-perceived health and low disease awareness, possibly making the subjects less adherent to study medication. We suggest that in pharmacogenetic research, extreme non-responders should be excluded to overcome the problem that non-adherence is investigated instead of non-responsiveness. PMID- 26686872 TI - Salvage abdominoperineal excisions in recurrent anal cancer--impact of different reconstruction techniques on outcome, morbidity, and complication rates. AB - BACKGROUND: Squamous cell cancer of the anus (SCCA) is a rare disease of the gastrointestinal tract. Even though chemoradiation therapy is the treatment of choice, a substantial number of patients develop recurrent cancers or present with persisting SCCA. Therefore, abdominoperineal excisions as a salvage therapy are the only chance of cure. PATIENTS AND METHODS: Hospital files of all patients with recurrent squamous cell carcinoma of the anus who underwent abdominoperineal excision performed at the Department of General and Visceral Surgery of the University Hospital Frankfurt between January 2003 and December 2013 were retrospectively reviewed. RESULTS: Fourteen (nine males, five females) patients underwent abdominoperineal resections for recurrent SCCA. In six patients, the pelvic floor was closed by direct suture, four patients underwent reconstruction using a vertical rectus abdominis myocutaneous (VRAM) flap, and four patients received a gluteal myocutaneous flap. Patients receiving flap-mediated closure revealed a median hospital stay of 26 days (range 13-60 days) compared to 11 days (range 9-30 days) in patients with direct closure (p = 0.01). Two patients (14%) suffered from wound infections (Dindo-Clavien II), whereas three patients (21%) underwent up to seven reoperations for breakdown of their wounds and/or laparotomies (Dindo-Clavien IIIb). The calculated 5-year survival rate was 86%. Patients with rpT0/T1 stage had a significantly longer survival compared to patients presenting with rpT2/T3/T4 tumors. CONCLUSION: Abdominoperineal excisions in patients with recurrent SCCA can provide long-term local control and survival. The complication rate is not associated with the closure technique employed, but patients undergoing flap-mediated closure revealed a significantly longer hospital stay. PMID- 26686874 TI - Surgical mortality audit data validity. AB - BACKGROUND: Surgical audits provide constructive feedback to individual surgeons, hospitals and other healthcare sector professionals. Audits identify deficiencies in treatment processes, evaluate practice trends and detect practice gaps. The credibility and validity of the Queensland Audit of Surgical Mortality (QASM) relies on the accuracy of its data. METHODS: To determine the validity of routine reporting of surgical information to QASM, surgical case forms were compared against medical records (considered the gold standard). Data were extracted by a trained medical research assistant. QASM forensically reviewed 896 of a total of 5636 deaths in 20 Queensland public hospitals between 2008 and 2013. Concordance between the surgical case form and the relevant medical record was determined for 27 objective items. RESULTS: Overall concordance was 98.2%. The median concordance was 100% (interquartile range 87-100%). Cases with discordance were few and in these, most had only one discordant item. Discordances were mainly omissions. CONCLUSION: The QASM surgical case form is a reliable data collection tool that provides high-quality data. QASM objective data can be confidently regarded as accurate and therefore reliable for use in publications, reports and case studies. PMID- 26686873 TI - Robot-assisted surgery for the radical treatment of deep infiltrating endometriosis with colorectal involvement: short- and mid-term surgical and functional outcomes. AB - PURPOSE: Sexual and urinary dysfunctions are complications in radical treatment of deep infiltrating endometriosis (DIE) with colorectal involvement. The aim of this article is to report the preliminary results of our single-institution experience with robotic treatment of DIE, evaluating intraoperative and postoperative surgical outcomes and focusing on the impact of this surgical approach on autonomic functions such as urogenital preservation and sexual well being. METHODS: From January 2011 through December 2013, a case series of 10 patients underwent robotic radical treatment of DIE with colorectal resection using the da Vinci System. Surgical data were evaluated, together with perioperative urinary and sexual function as assessed by means of self administered validated questionnaires. RESULTS: None of the patients reported significant postoperative complications. Questionnaires concerning sexual well being, urinary function, and impact of symptoms on quality of life demonstrated a slight worsening of all parameters 1 month after surgery, while data were comparable to the preoperative period 1 year after surgery. Dyspareunia was the only exception, as it was significantly improved 12 months after surgery. CONCLUSIONS: Robot-assisted surgery seems to be advantageous in highly complicated procedures where extensive dissection and proper anatomy re establishment is required, as in DIE with colorectal involvement. Our preliminary results show that robot-assisted surgery could be associated with a low risk of complications and provide good preservation of urinary function and sexual well being. PMID- 26686875 TI - The connection Between Plasma Protein Binding and Acute Toxicity as Determined by the LD50 Value. AB - Preclinical Research A dataset of three drug classes (acids, bases, and neutrals) with LD50 values in mice was analysed to investigate a possible connection between high plasma protein binding and acute toxicity. Initially, it was found that high plasma protein binding was associated with toxicity for acids and neutrals, but after compensating for differences in lipophilicity, plasma protein binding was found not to be associated with toxicity. The therapeutic index established by the quotient between mouse LD50 and the defined daily dose was unaffected by both lipophilicity and plasma protein binding. PMID- 26686876 TI - Improved Weight-Bearing Symmetry for Transfemoral Amputees During Standing Up and Sitting Down With a Powered Knee-Ankle Prosthesis. AB - OBJECTIVE: To test a new user-modulated control strategy that enables improved control of a powered knee-ankle prosthesis during sit-to-stand and stand-to-sit movements. DESIGN: Within-subject comparison study. SETTING: Gait laboratory. PARTICIPANTS: Unilateral transfemoral amputees (N=7; 4 men, 3 women) capable of community ambulation. INTERVENTIONS: Subjects performed 10 repetitions of sit-to stand and stand-to-sit with a powered knee-ankle prosthesis and with their prescribed passive prosthesis in a randomized order. With the powered prosthesis, knee and ankle power generation were controlled as a function of weight transferred onto the prosthesis. MAIN OUTCOME MEASURES: Vertical ground reaction force limb asymmetry and durations of movement were compared statistically (Wilcoxon signed-rank test, alpha=.05). RESULTS: For sit-to-stand, peak vertical ground reaction forces were significantly less asymmetric using the powered prosthesis (mean, 19.3%+/-11.8%) than the prescribed prosthesis (57.9%+/-13.5%; P=.018), where positive asymmetry values represented greater force through the intact limb. For stand-to-sit, peak vertical ground reaction forces were also significantly less asymmetric using the powered prosthesis (28.06%+/-11.6%) than the prescribed prosthesis (48.2%+/-16%; P=.028). Duration of movement was not significantly different between devices (sit-to-stand: P=.18; stand-to-sit: P=.063). CONCLUSIONS: Allowing transfemoral amputees more control over the timing and rate of knee and ankle power generation enabled users to stand up and sit down with their weight distributed more equally between their lower limbs. Increased weight bearing on the prosthetic limb may make such activities of daily living easier for transfemoral amputees. PMID- 26686877 TI - Energy Expenditure and Cost During Walking After Stroke: A Systematic Review. AB - OBJECTIVES: To systematically review the evidence to determine energy expenditure (EE) in volume of oxygen uptake (VO2) (mL/kg/min) and energy cost in oxygen uptake per meter walked (VO2/walking speed; mL/kg/m) during walking poststroke and how it compares with healthy controls; and to determine how applicable current exercise prescription guidelines are to stroke survivors. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and CINAHL were searched on October 9, 2014, using search terms related to stroke and EE. Additionally, we screened reference lists of eligible studies. STUDY SELECTION: Two independent reviewers screened titles and abstracts of 2115 identified references. After screening the full text of 144 potentially eligible studies, we included 29 studies (stroke survivors: n=501, healthy controls: n=123), including participants with confirmed stroke and a measure of VO2 during walking using breath-by-breath analysis. Studies with (9 studies) and without (20 studies) a healthy control group were included. DATA EXTRACTION: Two reviewers independently extracted data using a standard template, including patient characteristics, outcome data, and study methods. DATA SYNTHESIS: Mean age of stroke survivors was 57 years (range, 40-67y). Poststroke EE was highly variable across studies and could not be pooled because of high heterogeneity. EE during steady-state overground walking at matched speeds was significantly higher in stroke survivors than healthy controls (mean difference in VO2, 4.06 mL/kg/min; 95% confidence interval [CI], 2.21-5.91; 1 study; n=26); there was no significant group difference at self-selected speeds. Energy cost during steady-state overground walking was higher in stroke survivors at both self-selected (mean difference, .47 mL/kg/m; 95% CI, .29-.66; 2 studies; n=38) and matched speeds compared with healthy controls (mean difference, .27 mL/kg/m; 95% CI, .03-.51; 1 study; n=26). CONCLUSIONS: Stroke survivors expend more energy during walking than healthy controls. Low-intensity exercise as described in guidelines might be at a moderate intensity level for stroke survivors; there is a need for stroke specific exercise guidelines. PMID- 26686878 TI - Partially nested designs in psychotherapy trials: A review of modeling developments. AB - OBJECTIVE: Individually-randomized psychotherapy trials are often partially nested. For instance, individuals assigned to a treatment arm may be clustered into therapy groups for purposes of treatment administration, whereas individuals assigned to a wait-list control are unclustered. The past several years have seen rapid expansion and investigation of methods for analyzing partially nested data. Yet partial nesting often remains ignored in psychotherapy trials. METHODS: This review integrates and disseminates developments in the analysis of partially nested data that are particularly relevant for psychotherapy researchers. RESULTS: First, we differentiate among alternative partially nested designs. Then, we present adaptations of multilevel model specifications that accommodate each design. Next, we address how moderation by treatment as well as mediation of the treatment effect can be investigated in partially nested designs. Model fitting results, annotated software syntax, and illustrative data sets are provided and key methodological issues are discussed. CONCLUSIONS: We emphasize that cluster-level variability in the treatment arm need not be considered a nuisance; it can be modeled to yield insights about the treatment process. PMID- 26686879 TI - Coats' disease and retrobulbar haemodynamics. AB - PURPOSE: To study the retrobulbar haemodynamics in patients with Coats' disease. METHODS: The clinical study included 43 patients with Coats' disease. Using colour Doppler imaging, we measured the blood flow velocity in the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA), and recorded the peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), pulsatility index (PI) and resistance indexes (RI). The unaffected contralateral eyes served as control group. The disease was graded into four stages. RESULTS: Compared to the contralateral eyes, the Coats' disease affected eyes showed for the CRA a significant decrease in PSV (7.08 +/- 1.38 cm/s versus 8.64 +/- 1.45 cm/s; p < 0.001), EDV (2.03 +/- 0.41 cm/s versus 2.52 +/- 0.62 cm/s; p < 0.001) and TAMX (3.67 +/- 0.96 cm/s versus 4.40 +/- 1.22 cm/s; p = 0.003) and for the PCA a significant decrease in PSV (9.15 +/- 1.87 cm/s versus 10.14 +/- 1.61 cm/s; p = 0.01). Subgroup analysis revealed that the decrease in haemodynamic parameters existed mainly in patients with stage 3A2 and stage 3B of Coats' disease. CONCLUSIONS: As measured by colour Doppler imaging, the retrobulbar blood vessels showed decreased haemodynamic parameters in patients with Coats' disease on the affected side as compared to the contralateral unaffected side, in particular in advanced stages of the disease. Future studies may address the causes and effects of these haemodynamic changes. PMID- 26686881 TI - Trends in Measures of Childhood Obesity in Korea From 1998 to 2012. AB - BACKGROUND: During the last several decades, the number of children who are overweight or obese has reached alarming levels worldwide. The purpose of the present study was to examine trends in measures of childhood obesity among Korean children aged 2-19 from 1998 to 2012. METHODS: Height, weight, and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Age adjusted means of WC and BMI were compared between years. We used three international criteria (International Obesity Task Force [IOTF], World Health Organization [WHO], United States Centers for Disease Control and Prevention [CDC]) and a Korean national reference standard (Korea Centers for Disease Control and Prevention [KCDC]) to calculate age-standardized prevalence of childhood overweight and obesity. RESULTS: Despite differences in absolute prevalence of childhood overweight and obesity according to the four different criteria, the time trends of prevalence were generally similar across criteria. The prevalence of childhood overweight and obesity generally stabilized from 2001 2012 in both boys and girls. WC decreased from 2001-2012 in both boys and girls aged 2-19. CONCLUSIONS: Further studies exploring the factors causing plateaued trends of childhood obesity measures are needed to implement effective policies for reducing the prevalence of childhood overweight and obesity. PMID- 26686880 TI - Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. AB - The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package ('Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes. PMID- 26686882 TI - Associations Between Fine Particulate Matter Components and Daily Mortality in Nagoya, Japan. AB - BACKGROUND: Seasonal variation and regional heterogeneity have been observed in the estimated effect of fine particulate matter (PM2.5) mass on mortality. Differences in the chemical compositions of PM2.5 may cause this variation. We investigated the association of the daily concentration of PM2.5 components with mortality in Nagoya, Japan. METHODS: We combined daily mortality counts for all residents aged 65 years and older with concentration data for PM2.5 mass and components in Nagoya from April 2003 to December 2007. A time-stratified case crossover design was used to examine the association of daily mortality with PM2.5 mass and each component (chloride, nitrate, sulfate, sodium, potassium, calcium, magnesium, ammonium, elemental carbon [EC], and organic carbon [OC]). RESULTS: We found a stronger association between mortality and PM2.5 mass in transitional seasons. In analysis for each PM2.5 component, sulfate, nitrate, chloride, ammonium, potassium, EC, and OC were significantly associated with mortality in a single-pollutant model. In a multi-pollutant model, an interquartile range increase in the concentration of sulfate was marginally associated with an increase in all-cause mortality of 2.1% (95% confidence interval, -0.1 to 4.4). CONCLUSIONS: These findings suggest that some specific PM components have a more hazardous effect than others and contribute to seasonal variation in the health effects of PM2.5. PMID- 26686883 TI - Prevalence of Infant Shaking Among the Population as a Baseline for Preventive Interventions. PMID- 26686896 TI - Fragment quantum chemical approach to geometry optimization and vibrational spectrum calculation of proteins. AB - Geometry optimization and vibrational spectra (infrared and Raman spectra) calculations of proteins are carried out by a quantum chemical approach using the EE-GMFCC (electrostatically embedded generalized molecular fractionation with conjugate caps) method (J. Phys. Chem. A, 2013, 117, 7149). The first and second derivatives of the EE-GMFCC energy are derived and employed in geometry optimization and vibrational frequency calculations for several test systems, including a polypeptide ((GLY)6), an alpha-helix (AKA), a beta-sheet (Trpzip2) and ubiquitin (76 residues with 1231 atoms). Comparison of the present results with those obtained from full system QM (quantum mechanical) calculations shows that the EE-GMFCC approach can give accurate molecular geometries, vibrational frequencies and vibrational intensities. The EE-GMFCC method is also employed to simulate the amide I vibration of proteins, which has been widely used for the analysis of peptide and protein structures, and the results are in good agreement with the experimental observations. PMID- 26686897 TI - The risk of life-threatening ventricular arrhythmias in presence of high intensity endurance exercise along with chronic administration of nandrolone decanoate. AB - Anabolic steroids used to improve muscular strength and performance in athletics. Its long-term consumption may induce cardiovascular adverse effects. We assessed the risk of ventricular arrhythmias in rats which subjected to chronic nandrolone plus high-intensity endurance exercise. Animals were grouped as; control (CTL), exercise (Ex): 8 weeks under exercise, vehicle group (Arach): received arachis oil, and Nan group: received nandrolone decanoate 5 mg/kg twice a week for 8 weeks, Arach+Ex group, and Nan+Ex. Finally, under anesthesia, arrhythmia was induced by infusion of 1.5 MUg/0.1 mL/min of aconitine IV and ventricular arrhythmias were recorded for 15 min. Then, animals' hearts were excised and tissue samples were taken. Nandrolone plus exercise had no significant effect on blood pressure but decreased the heart rate (P<0.01) and increased the RR (P<0.01) and JT intervals (P<0.05) of electrocardiogram. Nandrolone+exercise significantly increased the ventricular fibrillation (VF) frequency and also decreased the VF latency (P<0.05 versus CTL group). Combination of exercise and nandrolone could not recover the decreasing effects of nandrolone on animals weight gain but, it enhanced the heart hypertrophy index (P<0.05). In addition, nandrolone increased the level of hydroxyproline (HYP) and malondialdehyde (MDA) but had not significant effect on glutathione peroxidase of heart. Exercise only prevented the effect of nandrolone on HYP. Nandrolone plus severe exercise increases the risk of VF that cannot be explained only by the changes in redox system. The intensification of cardiac hypertrophy and prolongation of JT interval may be a part of involved mechanisms. PMID- 26686885 TI - Build to understand: synthetic approaches to biology. AB - In this review we discuss how synthetic biology facilitates the task of investigating genetic circuits that are observed in naturally occurring biological systems. Specifically, we give examples where experimentation with synthetic gene circuits has been used to understand four fundamental mechanisms intrinsic to development and disease: multistability, stochastic gene expression, oscillations, and cell-cell communication. Within each area, we also discuss how mathematical modeling has been employed as an essential tool to guide the design of novel gene circuits and as a theoretical basis for exploring circuit topologies exhibiting robust behaviors in the presence of noise. PMID- 26686898 TI - Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities. AB - Novel 16-hydroxymethyl-19-nortestosterone diastereomers were prepared by Birch reduction from the corresponding 3-methoxy-16-hydroxymethylestra-1,3,5(10)-trien 17-ol isomers with known configurations. The synthesized compounds are 16alpha- and 16beta-hydroxymethyl-substituted 19-nortestosterone and their 17alpha epimers. To prepare 17alpha-19-nortestosterone, the Mitsunobu inversion reaction of 19-nortestosterone with different alkyl and aryl carboxylic acids was chosen. Deacylation of the new compounds by the Zemplen method yielded the required 17alpha-19-nortestosterone. The antiproliferative activities of the structurally related compounds were determined in vitro through microculture tetrazolium assays on a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF 7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines. The 17alpha epimer of 19-nortestosterone demonstrated considerable activity, selectively for HeLa cells, with a calculated IC50 of 0.65 MUM. The reference compound, cisplatin, displayed an order of magnitude higher IC50 (12.4 MUM). The cancer selectivity of 17alpha-19-nortestosterone was tested by MTT assay performed with noncancerous human fibroblast cell line MRC-5. The results indicated that 17alpha 19-nortestosterone selectively disturbs the viability of HeLa cells without greatly affecting other cancer cell types and intact fibroblasts. PMID- 26686899 TI - Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers. AB - There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 +/- 101.3 (mean +/ sd) at 8.00 h to 198.9 +/- 90.7 pg/mL at 18.00 h; p<0.0001, and young females from 401.6 +/- 149.5 to 215.4 +/- 95.3 pg/mL; p<0.001. In older males DHEA reduced from 267.5 +/- 32.4 to 132.5 +/- 46.7 pg/mL; p<0.001, and older females from 147.7 +/- 78.1 to 89.5 +/- 29.1 pg/mL; p=0.05. DHEA levels on 2 non consecutive days showed some variations but this was not significant. Aerobic exercise has significantly increased DHEA levels at 2 time points of the day (p=0.05) in male subjects. In conclusion, our study showed a clear daily circadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. PMID- 26686900 TI - Stepping stone or stumbling block? Mode 2 knowledge production in sustainability science. AB - The concept of Mode 2 has often been seen as especially applicable to fields addressing grand challenges, such as climate change. Being a relatively new field interdisciplinary in its approach, and focused on addressing such issues sustainability science would appear to be a case in point. The aim of this paper is twofold: 1) to explore the perceived relation between Mode 2 and sustainability science, and 2) to advance the discussion of Mode 2 from a philosophical perspective. To address these questions we focus on three characteristic features of Mode 2: the notion of a distinct, but evolving framework; boundary crossing; and a problem solving capacity "on the move". We report the results of a survey carried out amongst leading sustainability scientists. The survey gives insight into the scientists' perception of Mode 2, their perception of their own field of sustainability science and the relation between the two. The free text answers reveal a tension within the field of sustainability science: with developments both towards Mode 1 and Mode 2 science. We conclude that the implementation of inter- and trans-disciplinarity is challenged by institutional and conceptual factors alike. PMID- 26686901 TI - Rh(II)-Catalyzed formation of pyrrolo[2,3-b]quinolines from azide methylenecyclopropanes and isonitriles. AB - Azide-methylenecyclopropanes (azide-MCPs) underwent an intermolecular cyclization with isonitriles catalyzed by a Rh(II) complex to produce a series of pyrrolo[2,3 b]quinolines in moderate to good yields via carbodiimide intermediates. Moreover, synthetic applications of these products to construct structurally novel and useful heterocycles have also been achieved. PMID- 26686903 TI - Self-deposition of Pt nanoparticles on graphene woven fabrics for enhanced hybrid Schottky junctions and photoelectrochemical solar cells. AB - In this study, we demonstrated a self-deposition method to deposit Pt nanoparticles (NPs) on graphene woven fabrics (GWF) to improve the performance of graphene-on-silicon solar cells. The deposition of Pt NPs increased the work function of GWF and reduced the sheet resistance of GWF, thereby improving the power conversion efficiency (PCE) of graphene-on-silicon solar cells. The PCE (>10%) was further enhanced via solid electrolyte coating of the hybrid Schottky junction in the photoelectrochemical solar cells. These results suggest that the combination of self-deposition of Pt NPs and solid-state electrolyte coating of graphene-on-silicon is a promising way to produce high performance graphene-on semiconductor solar cells. PMID- 26686902 TI - miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity. AB - Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation. PMID- 26686905 TI - The utility of mock oral examinations in preparation for the American Board of Surgery certifying examination. AB - BACKGROUND: Determine the utility of mock oral examinations in preparation for the American Board of Surgery certifying examination (ABS CE). METHODS: Between 2002 and 2012, blinded data were collected on 63 general surgery residents: 4th and 5th-year mock oral examination scores, first-time pass rates on ABS CE, and an online survey. RESULTS: Fifty-seven residents took the 4th-year mock oral examination: 30 (52.6%) passed and 27 (47.4%) failed, with first-time ABS CE pass rates 93.3% and 81.5% (P = .238). Fifty-nine residents took the 5th-year mock oral examination: 28 (47.5%) passed and 31 (52.5%) failed, with first-time ABS CE pass rates 82.1% and 93.5% (P = .240). Thirty-eight responded to the online survey, 77.1% ranked mock oral examinations as very or extremely helpful with ABS CE preparation. CONCLUSIONS: Although mock oral examinations and ABS CE passing rates do not directly correlate, residents perceive the mock oral examinations to be helpful. PMID- 26686906 TI - Identifying the need for and content of an advanced laparoscopic skills curriculum: results of a national survey. AB - BACKGROUND: A recent survey of fellowship directors suggested significant deficits in the technical laparoscopic skills of graduated general surgery residents. Our aim was to define the need for and possible content of a simulation-based curriculum in advanced laparoscopic skills (ALS). METHODS: An anonymous online survey was distributed to all Fellowship Council program directors (PDs), current fellows, and recent fellowship graduates. The survey was designed to assess the perceived need for, possible content of, and implementation challenges to an ALS curriculum. Recently developed simulation based advanced laparoscopic tasks included off-angle camera work and restricted space suturing. Images and descriptions of these tasks were evaluated by respondents, and suggestions for modifications or improvements solicited via free text response. RESULTS: Of 186 respondents (response rate: 64%), 40% were current fellows, 22% were fellowship graduates, and 37% were PDs. Respondents primarily self-identified as minimally invasive and/or bariatric surgeons (78%) and hepatobiliary surgeons (12%). Most respondents (73%) identified a need for an ALS curriculum. All 3 respondent groups cited laparoscopic needle positioning and suturing (78%) and bimanual coordination during dissection and retraction (72%) as the skills in most need of improvement. In addition, most of the responding PDs identified "lack of familiarity with anatomy and procedure" (74% of PDs) and "lack of proficiency at laparoscopic bowel anastomosis" (59% of PDs) as problem areas. Respondents felt that successful implementation of an ALS curriculum depended on both overall feasibility and the ability for repeated practice and should not be dependent on cost. Thematic analysis of free responses revealed the following priorities for possible ALS skills and tasks: (1) difficult dissections and exposures, (2) forehand and/or backhand and suturing under tension, (3) nondominant hand drills, (4) working with an off-set camera, and (5) suturing and handling fragile tissue with properties similar to peritoneum or bowel. CONCLUSIONS: We present survey results identifying several specific ALS set deficits among graduating general surgery residents, including advanced suturing, bimanual coordination, and managing difficult anatomy. Next, the results of this needs assessment will be used to develop an advanced laparoscopic curriculum for residents entering minimally invasive surgery fellowships and careers. PMID- 26686904 TI - Windows of sensitivity to toxic chemicals in the motor effects development. AB - Many chemicals currently used are known to elicit nervous system effects. In addition, approximately 2000 new chemicals introduced annually have not yet undergone neurotoxicity testing. This review concentrated on motor development effects associated with exposure to environmental neurotoxicants to help identify critical windows of exposure and begin to assess data needs based on a subset of chemicals thoroughly reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) in Toxicological Profiles and Addenda. Multiple windows of sensitivity were identified that differed based on the maturity level of the neurological system at the time of exposure, as well as dose and exposure duration. Similar but distinct windows were found for both motor activity (GD 8 17 [rats], GD 12-14 and PND 3-10 [mice]) and motor function performance (insufficient data for rats, GD 12-17 [mice]). Identifying specific windows of sensitivity in animal studies was hampered by study designs oriented towards detection of neurotoxicity that occurred at any time throughout the developmental process. In conclusion, while this investigation identified some critical exposure windows for motor development effects, it demonstrates a need for more acute duration exposure studies based on neurodevelopmental windows, particularly during the exposure periods identified in this review. PMID- 26686907 TI - The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates. AB - In many drug delivery strategies, an inefficient transfer of macromolecules such as proteins and nucleic acids to the cytosol often occurs because of their endosomal entrapment. One of the methods to overcome this problem is photochemical internalization, which is achieved using a photosensitizer and light to facilitate the endosomal escape of the macromolecule. In this study, we examined the molecular mechanism of photochemical internalization of cell penetrating peptide-cargo (macromolecule)-photosensitizer conjugates. We measured the photophysical properties of eight dyes (photosensitizer candidates) and determined the respective endosomal escape efficiencies using these dyes. Correlation plots between these factors indicated that the photogenerated (1)O2 molecules from photosensitizers were highly related to the endosomal escape efficiencies. The contribution of (1)O2 was confirmed using (1)O2 quenchers. In addition, time-lapse fluorescence imaging showed that the photoinduced endosomal escape occurred at a few seconds to a few minutes after irradiation (much longer than (1)O2 lifetime), and that the pH increased in the endosome prior to the endosomal escape of the macromolecule. PMID- 26686908 TI - The complement system in cancer: Ambivalence between tumour destruction and promotion. AB - Constituting a part of the innate immune system, the complement system consists of over 50 proteins either acting as part of a 3-branch activation cascade, a well-differentiated regulatory system in fluid phase or on each tissue, or as receptors translating the activation signal to multiple cellular effector functions. Complement serves as first line of defence against infections from bacteria, viruses and parasites by orchestrating the immune response through opsonisation, recruitment of immune cells to the site of infection and direct cell lysis. Complement is generally recognised as a protective mechanism against the formation of tumours in humans, but is often limited by various resistance mechanisms interfering with its cytotoxic action, now considered as a great barrier of successful antibody-based immunotherapy. However, recent studies also indicate a pro-tumourigenic potential of complement in certain cancers and under certain conditions. In this review, we present recent findings on the possible dual role of complement in destroying cancer, especially if resistance mechanisms are blocked, but also under certain inflammatory conditions-promoting tumour development. PMID- 26686909 TI - Chitinases and immunity: Ancestral molecules with new functions. AB - Chitinases belonging to 18 glycosyl hydrolase family is an ancient gene family that is widely expressed from prokaryotes to eukaryotes. In humans, despite the absence of endogenous chitin, a number of Chitinases and Chitinase-like Proteins (C/CLPs) have been identified. Chitinases with enzymatic activity have a chitin binding domain containing six cysteine residues responsible for their binding to chitin. In contrast, CLPs do not contain such typical chitin-binding domains, but still can bind to chitin with high affinity. Molecular phylogenetic analyses suggest that active Chitinases result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. For the majority of the mammalian chitinases the last decades have witnessed the appearance of a substantial number of studies describing their expression differentially regulated during more specific immunologic activities. It is becoming increasingly clear that their function is not exclusive to catalyse the hydrolysis of chitin producing pathogens, but include crucial role in bacterial infections and inflammatory diseases. Here we provide an overview of all family members to shed light on the mechanisms and molecular interactions of Chitinases and CLPs in relation to immune response regulation, in order to delineate their future utilization as diagnostic and prognostic markers for numerous diseases. PMID- 26686910 TI - Anti-inflammatory potential of beta-cryptoxanthin against LPS-induced inflammation in mouse Sertoli cells. AB - beta-cryptoxanthin (CX), a major carotenoid pigment, can inhibit inflammatory gene expression in mice with nonalcoholic steatohepatitis. In the present study, we examined the anti-inflammatory effects of CX on lipopolysaccharide (LPS) induced inflammation in mouse primary Sertoli cells and the possible molecular mechanisms behind its effects. The results showed that CX significantly inhibited LPS-induced decreases in cell viability and in the percentage of apoptotic cells. Moreover, CX inhibited the LPS-induced up-regulation of tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10), interleukin-6 (IL-6) and interleukin 1beta (IL-1beta) in Sertoli cells. In addition, CX significantly limited the LPS induced down-regulation of AR, HSF2, CREB, FSHR, INHBB and ABP in Sertoli cells. Western blot analysis showed that CX significantly suppressed NF-kappaB (p65) activation as well as MAPK phosphorylation. All the results suggested that CX suppressed inflammation, possibly associated with the NF-kappaB activation and MAPK of phosphorylation. Thus, CX may possess therapeutic potential against inflammation-related diseases. PMID- 26686911 TI - Multivariate analysis of 200-m front crawl swimming performance in young male swimmers. AB - The aim of the present study was to evaluate the biomechanical (stroke rate, stroke length, and stroke index), anthropometrical (body height, body mass, body mass index, arm span, shoulders width, thigh, leg and upper arm lengths), and muscle architectural (muscle thickness, pennation angle, and fascicle length) parameters as predictors of 200-m front crawl swimming performance in young male swimmers. Twenty-two county level male swimmers (mean +/-SD: age: 14.52 +/- 0.77 years; body height: 173 +/- 5 m; body mass: 60.5 +/- 5.7 kg) performed a 200-m front crawl swimming test in a 25-m pool. Stepwise regression analysis revealed that biomechanical parameters (87%) characterized best 200-m front crawl swimming performance, followed by anthropometrical (82%) and muscle architectural (72%) parameters. Also, stroke length (R2 = 0.623), body height (R2 = 0.541), fascicle length of Triceps Brachii (R2 = 0.392) were the best single predictors that together explained 92% of the variability of the 200-m front crawl swimming performance in these swimmers. As a conclusion, with respect to higher performance prediction power of biomechanical parameters, technique should represent the core of the training program at these ages. In addition, these findings could be used for male young swimmers selection and talent identification. PMID- 26686912 TI - Survival impact of postoperative body mass index in gastric cancer patients undergoing gastrectomy. AB - BACKGROUND: The relationship between preoperative body mass index (BMI) and the survival of postoperative gastric cancer patients is not clear. Furthermore, the survival impact with postoperative BMI is not known, even though weight loss is inevitable after gastrectomy. METHODS: Patients who underwent gastrectomy for gastric cancer between 2000 and 2008 were included in the study (n = 1909). Patients were divided into three groups based on their BMIs: low (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), and high BMI (>= 25.0 kg/m(2)). Patient survival was compared according to BMI at two time points: baseline and 1 year after surgery. RESULTS: Regarding BMI 1 year after surgery, overall survival, disease-specific survival, and recurrence-free survival were longer in the high BMI group than the low and normal BMI groups. In a Cox proportional hazards model, adjusting for the patient's age, sex, type of surgery, tumour stage, histology, curative resection, and BMI at baseline, a high BMI 1 year after surgery was associated with lower overall mortality compared to normal BMI (hazard ratio 0.51; 95% confidence interval, 0.26-0.98). However, BMI at baseline was not an independent prognostic factor. CONCLUSION: BMI 1 year after surgery significantly predicted the long term survival of patients with gastric cancer compared with the preoperative BMI. PMID- 26686913 TI - Human Telomere G-Quadruplexes with Five Repeats Accommodate 8-Oxo-7,8 dihydroguanine by Looping out the DNA Damage. AB - Inflammation and oxidative stress generate free radicals that oxidize guanine (G) in DNA to 8-oxo-7,8-dihydroguanine (OG), and this reaction is prominent in the G rich telomere sequence. In telomeres, OG is not efficiently removed by repair pathways allowing its concentration to build, surprisingly without any immediate negative consequences to stability. Herein, OG was synthesized in five repeats of the human telomere sequence (TTAGGG)n, at the 5'-G of the 5'-most, middle, and 3' most G tracks, representing hotspots for oxidation. These synthetic oligomers were folded in relevant amounts of K(+)/Na(+) to adopt hybrid G-quadruplex folds. The structural impact of OG was assayed by circular dichroism, thermal melting, (1)H NMR, and single-molecule profiling by the alpha-hemolysin nanopore. On the basis of these results, OG was well accommodated in the five-repeat sequences by looping out the damaged G track to allow the other four tracks to adopt a hybrid G-quadruplex. These results run counter to previous studies with OG in four repeat telomere sequences that found OG to be highly destabilizing and causing significant reorientation of the fold. When taking a wider view of the human telomere sequence and considering additional repeats, we found OG to cause minimal impact on the structure. The plasticity of this repeat sequence addresses how OG concentrations can increase in telomeres without immediate telomere instability or attrition. PMID- 26686914 TI - Intrauterine device placement at 3 versus 6 weeks postpartum: a randomized trial. AB - OBJECTIVE: To investigate whether early placement of an intrauterine device (IUD) at 3 weeks after delivery, compared to placement at 6 weeks, is associated with greater use at 3 months postpartum. STUDY DESIGN: This prospective randomized, controlled trial enrolled inpatient postpartum women intending to use intrauterine contraception. Participants were assigned to an early (3 week) or standard (6 week) postpartum visit with IUD placement and were followed for 6 months. We used transvaginal ultrasonography to confirm placement and measure uterine dimensions. We measured pain with IUD insertion and satisfaction with IUD timing using 100-mm visual analog scales. Data were analyzed based on randomization and actual timing of insertion (18-24 vs. 39-45 days). RESULTS: Between February 2012 and December 2013, 201 subjects were enrolled (early=101; standard=100). Most participants returned for IUD placement as scheduled; 70.1% (53/75) in the early group, 74.3% (58/78) in the standard group (p=.06). IUD use did not differ between groups at 3 months (73/100, 73.0% and 73/97, 75.3%, respectively, p=.72) or 6 months (80.3% and 82.8%, p=.71) amongst those women for whom follow-up was available. Women randomized to 6-week insertion were more likely to have resumed intercourse prior to the IUD appointment (15/64, 23.4% vs. 5/68, 7.3%, p=.01). Pain with insertion (19.9 vs. 25.1, respectively, p=.21) and satisfaction (89.6 vs. 93.4, respectively, p=.23) did not vary based on actual timing of insertion. CONCLUSION: Offering IUD placement at 3 weeks postpartum compared to standard scheduling at 6 weeks does not result in increased use at 3 months. However, early IUD placement is acceptable to women and without increased pain. IMPLICATIONS: This study demonstrates that IUD placement as early as 3 weeks postpartum is feasible. Larger studies are needed to evaluate risks and benefits of IUD placement at this early interval. While earlier timing does not result in increased IUD uptake, early placement should be explored as an option since many women resume intercourse before 6 weeks. PMID- 26686915 TI - Editorial. PMID- 26686916 TI - High-yield synthesis of strong photoluminescent N-doped carbon nanodots derived from hydrosoluble chitosan for mercury ion sensing via smartphone APP. AB - Photoluminescent carbon nanodots (CNDs) have offered considerable potential to be used in biomedical and environmental fields including live cell imaging and heavy metal ion detection due to their superior quantum emission efficiencies, ability to be functionalized using a variety of chemistries and apparent absence of toxicity. However, to date, synthetic yield of CNDs derived from biomass via hydrothermal carbonization is quite low. We report here the synthesis of nitrogen doped carbon nanodots (N-doped CNDs) derived from hydrosoluble chitosan via hydrothermal carbonization. The synthetic yield could reach 38.4% which is 2.2 320 times increase compared with that from other biomass reported so far. These N doped CNDs exhibited a high quantum yield (31.8%) as a consequence of nitrogen incorporation coincident with multiple types of functional groups (C=O, O-H, COOH, and NH2). We further demonstrate applications of N-doped CNDs as probes for live cell multicolor imaging and heavy metal ion detection. The N-doped CNDs offered potential as mercury ion sensors with detection limit of 80nM. A smartphone application (APP) based on N-doped CNDs was developed for the first time providing a portable and low cost detection platform for detection of Hg(2+) and alert of heavy metal ions contamination. PMID- 26686917 TI - Simultaneous detection of multiple lower genital tract pathogens by an impedimetric immunochip. AB - Lower genital tract infections caused by both sexually and not-sexually transmitted pathogens in women are a key public health priority worldwide, especially in developing countries. Since standard analyses are time-consuming, appropriate therapeutic intervention is often neglected or delayed. Lab-on-chips and biosensors open new perspectives and offer innovative tools to simplify the diagnosis by medical staff, especially in countries with inadequate resources. Here we report a biosensing platform based on Electrochemical Impedance Spectroscopy (EIS) that allows multiplexed detection of Candida albicans, Streptococcus agalactiae and Chlamydia trachomatis with a single biochip, enabling a quick screening thanks to the presence of different immobilized antibodies, each specific for one of the different target pathogens. PMID- 26686918 TI - A graphene oxide-based FRET sensor for rapid and specific detection of unfolded collagen fragments. AB - The unstructured collagen species plays a critical role in a variety of important biological processes as well as pathological conditions. In order to develop novel diagnosis and therapies for collagen-related diseases, it is essential to construct simple and efficient methods to detect unfolded collagen fragments. We therefore have designed a FITC-labeled collagen mimic triple helical peptide, whose adsorption on the surface of GO effectively quenches its fluorescence. The newly constructed GO/FITC-GPO complex specifically detects unstructured collagen fragments, but not fully folded triple helix species. The detection shows a clear preference for the collagen targets with complementary GPO-rich sequences. The conformation-sensitive, sequence-specific GO-based approach can be applied as an efficient biosensor for rapid detection of unfolded collagen fragments at nM level, and may have great potential in drug screening for inhibitors of unfolded collagen. It may provide a prototype to develop GO-based assays to detect other important unstructured proteins involved in diseases. PMID- 26686919 TI - A novel electrochemical aptasensor for bisphenol A assay based on triple signaling strategy. AB - Based on a triple-signaling strategy, a novel electrochemical aptasensor has been developed for sensitive and selective detection of bisphenol A (BPA). The thiolated ferrocene (Fc)-modified BPA-binding aptamer probe (Fc-P) was immobilized on the gold electrode and then hybridized with the methylene blue (MB)-modified complementary DNA probe (MB-P) to form a rigid double-stranded DNA (ds-DNA). The specific interaction between BPA and Fc-P led to the release of MB P from the sensing interface and the conformational change of Fc-P. As a result, the oxidation peak currents of Fc and BPA increased with the increase of the concentration of target (BPA) according to the "signal-on" mode while that of MB decreased with the increase of the BPA concentration according to the "signal off" mode. By superimposing the triple signal changes, BPA was detected sensitively with a linear range from 1 pM to 100 pM. The detection limit is 0.19 pM, and much lower than that obtained by most of the reported electrochemical methods. The aptasensor also exhibited satisfactory specificity, selectivity, reproducibility and stability. By changing the specific aptamers, this strategy could be easily extended to detect other redox targets, showing promising applications in environmental analysis, food safety monitoring, and bioanalysis. PMID- 26686920 TI - G-quadruplex DNAzyme-based chemiluminescence biosensing platform based on dual signal amplification for label-free and sensitive detection of protein. AB - Detection of ultralow concentration of specific protein plays a key role in biotechnological applications and medical diagnostics. In this study, we demonstrate an amplified chemiluminescence biosensing platform for sensitive detection of protein. The biosensing platform ingeniously combines target catalyzed hairpin assembly and Exo III-assisted signal amplification. A catalytic G-quadruplex-hemin DNAzyme is further employed to stimulate the generation of chemiluminescence in the presence of luminol and H2O2. These designs together allow a high sensitivity for the biotarget, human alpha-thrombin, resulting in a detection limit of 0.92 pM, and it is much lower than previous reported studies. In addition, the proposed biosensing platform is versatile. By conjugating with various recognition units, it could be employed to sensitive detect various DNA binding proteins and might find wide applications in biomedical fields. PMID- 26686921 TI - Highly sensitive electrochemiluminescenc assay of acetylcholinesterase activity based on dual biomarkers using Pd-Au nanowires as immobilization platform. AB - One-dimensional Pd-Au nanowires (Pd-Au NWs) were prepared and applied to fabricate an electrochemiluminescence (ECL) biosensor for the detection of acetylcholinesterase (AChE) activity. Compared with single-component of Pd or Au, the bimetallic nanocomposite of Pd-Au NWs offers a larger surface area for the immobilization of enzyme, and displays superior electrocatalytic activity and efficient electron transport capacity. In the presence of AChE and choline oxidase (ChOx), acetylcholine (ATCl) is hydrolyzed by AChE to generate thiocholine, then thiocholine is catalyzed by ChOx to produce H2O2 in situ, which serves as the coreactant to effectively enhance the ECL intensity in luminol-ECL system. The detection principle is based on the inhibited AChE and reactivated AChE as dual biomarkers, in which AChE was inhibited by organophosphorus (OP) agents, and then reactivated by obidoxime. Such dual biomarkers method can achieve credible evaluation for AChE activity via providing AChE activity before and after reactivation. The liner range for AChE activity detection was from 0.025 U L(-1) to 25 KU L(-1) with a low detection limit down to 0.0083 U L(-1). PMID- 26686922 TI - Determination of cell metabolite VEGF165 and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe. AB - In this paper, we rationally design a novel G-quadruplex-selective luminescent iridium (III) complex for rapid detection of oligonucleotide and VEGF165 in microfluidics. This new probe is applied as a convenient biosensor for label-free quantitative analysis of VEGF165 protein from cell metabolism, as well as for studying the kinetics of the aptamer-protein interaction combination with a microfluidic platform. As a result, we have successfully established a quantitative analysis of VEGF165 from cell metabolism. Furthermore, based on the principles of hydrodynamic focusing and diffusive mixing, different transient states during kinetics process were monitored and recorded. Thus, the combination of microfluidic technique and G-quadruplex luminescent probe will be potentially applied in the studies of intramolecular interactions and molecule recognition in the future. PMID- 26686923 TI - A sandwich-type electrochemical immunosensor for carcinoembryonic antigen based on signal amplification strategy of optimized ferrocene functionalized Fe3O4@SiO2 as labels. AB - A sandwich-type electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) by using ferroferric oxide@silica amino groups (Fe3O4@SiO2-NH2) as carriers and gold nanoparticles-graphene oxide (GO-AuNPs) as platform. The Fe3O4@SiO2-NH2 surface was used as linked reagents for co-immobilization of ferrocenecarboxylic acid (Fc-COOH) and secondary anti CEA (Ab2) to prepare the signal probe, and it also could hasten the decomposition of hydrogen peroxide (H2O2) to amplify signals. Differential pulse voltammetry (DPV) was successfully used to quantify CEA. Under the optimized conditions, the designed immunosensor shows an excellent analytical performance wide dynamic response range of CEA concentration from 0.001 ng mL(-1) to 80 ng mL(-1) with a relatively low detection limit of 0.0002 ng mL(-1) (S/N=3), and high specificity and good reproducibility. The proposed immunosensor was successfully used to determine CEA in spiked human serum samples. PMID- 26686924 TI - Multifunctional reduced graphene oxide trigged chemiluminescence resonance energy transfer: Novel signal amplification strategy for photoelectrochemical immunoassay of squamous cell carcinoma antigen. AB - Herein, a photoelectrochemical (PEC) immunoassay is constructed for squamous cell carcinoma antigen (SCCA) detection using zinc oxide nanoflower-bismuth sulfide (Bi2S3) composites as photoactive materials and reduced graphene oxide (rGO) as signal labels. Horseradish peroxidase is used to block sites against nonspecific binding, and then participated in luminol-based chemiluminescence (CL) system. The induced CL emission is acted as an inner light source to excite photoactive materials, simplifying the instrument. A novel signal amplification strategy is stem from rGO because of the rGO acts as an energy acceptor, while luminol serves as a donor to rGO, triggering the CL resonance energy transfer phenomenon between luminol and rGO. Thus, the efficient CL emission to photoactive materials decreases. Furthermore, the signal amplification caused by rGO labeled signal antibodies is related to photogenerated electron-hole pairs: perfect matching of energy levels between rGO and Bi2S3 makes rGO a sink to capture photogenerated electrons from Bi2S3; the increased steric hindrance hinders the electron donor to the surface of Bi2S3 for reaction with the photogenerated holes. On the basis of the novel signal amplification strategy, the proposed immunosensor exhibits excellent analytical performance for PEC detection of SCCA, ranging from 0.8 pg mL(-1) to 80 ng mL(-1) with a low detection limit of 0.21 pg mL(-1). Meanwhile, the designed signal amplification strategy provides a general format for future development of PEC assays. PMID- 26686925 TI - Brain mimickers of myocardial infarction. PMID- 26686926 TI - An investigation of multimorbidity measures as risk factors for pneumonia in elderly frail patients admitted to hospital. AB - OBJECTIVES: To investigate the association of different chronic comorbidities, considered singularly and together in Cumulative Illness Rating Scale (CIRS) indexes, with pneumonia diagnosis in a group of elderly frail hospitalized patients. DESIGN AND METHODS: With a retrospective cohort design, all clinical records of frail (Rockwood >= 5) nonterminal patients >= 65 years old acutely admitted over a 8-month span in an internal medicine ward were evaluated. Pneumonia status and its categorization (community-acquired, CAP, vs healthcare associated, HCAP) were defined according to chest radiology findings and validated criteria. Chronic comorbidities, CIRS Comorbidity Score and CIRS Severity Index were collected for each participant through a standardized methodology. Multivariate logistic regression models were applied to assess the association of each comorbid condition or scores with pneumonia. RESULTS: 1199 patients (546 M, median age 81.9, IQR 72.8-87.9 years), of whom 239 with pneumonia (180 CAP, 59 HCAP) were evaluated. CIRS Comorbidity Score was significantly associated with pneumonia, both at an age- and sex-adjusted model and at a multivariate model (OR for each unitary increase 1.03, 95% CI 1.001 1.062, p=0.04), together with provenience from nursing home (OR 1.96, 95% CI 1.41 2.73, p<0.001). Among single comorbidities, only COPD (OR 2.7, 95% CI 1.9-3.6, p<0.001) and dementia (OR 2.3, 95% CI 1.7-3.3, p<0.001) were associated with pneumonia, while stroke, cancer, cardiovascular, chronic liver and kidney disease were not. CONCLUSIONS: In a small cohort of elderly frail hospitalized patients, measures of multimorbidity, like CIRS, are significantly associated with the risk of pneumonia. COPD and dementia are the main conditions concurring to define this risk. PMID- 26686927 TI - Falling in the elderly: Do statistical models matter for performance criteria of fall prediction? Results from two large population-based studies. AB - OBJECTIVE: To compare performance criteria (i.e., sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic curve and accuracy) of linear and non-linear statistical models for fall risk in older community-dwellers. METHODS: Participants were recruited in two large population-based studies, "Prevention des Chutes, Reseau 4" (PCR4, n=1760, cross-sectional design, retrospective collection of falls) and "Prevention des Chutes Personnes Agees" (PCPA, n=1765, cohort design, prospective collection of falls). Six linear statistical models (i.e., logistic regression, discriminant analysis, Bayes network algorithm, decision tree, random forest, boosted trees), three non-linear statistical models corresponding to artificial neural networks (multilayer perceptron, genetic algorithm and neuroevolution of augmenting topologies [NEAT]) and the adaptive neuro fuzzy interference system (ANFIS) were used. Falls >=1 characterizing fallers and falls >=2 characterizing recurrent fallers were used as outcomes. Data of studies were analyzed separately and together. RESULTS: NEAT and ANFIS had better performance criteria compared to other models. The highest performance criteria were reported with NEAT when using PCR4 database and falls >=1, and with both NEAT and ANFIS when pooling data together and using falls >=2. However, sensitivity and specificity were unbalanced. Sensitivity was higher than specificity when identifying fallers, whereas the converse was found when predicting recurrent fallers. CONCLUSIONS: Our results showed that NEAT and ANFIS were non-linear statistical models with the best performance criteria for the prediction of falls but their sensitivity and specificity were unbalanced, underscoring that models should be used respectively for the screening of fallers and the diagnosis of recurrent fallers. PMID- 26686928 TI - Selenomethionine, p-cyanophenylalanine pairs provide a convenient, sensitive, non perturbing fluorescent probe of local helical structure. AB - The use of selenomethionine (MSe)-p-cyanophenylalanine (FCN) pairs to probe protein structure is demonstrated. MSe quenches FCN fluorescence via electron transfer. Both residues can be incorporated recombinantly or by peptide synthesis. Time-resolved and steady-state fluorescence measurements demonstrate that MSe-FCN pairs provide specific local probes of helical structure. PMID- 26686929 TI - Spiromastilactones: A new class of influenza virus inhibitors from deep-sea fungus. AB - A new class of phenolic lactones with trivial names of spiromastilactones A-M (1 13) was isolated from a deep-sea derived Spiromastix sp. fungus. Their structures featured by various chlorination at aromatic rings were determined on the basis of extensive spectroscopic analyses. An antiviral assay revealed that most of the tested compounds exert inhibitory activity against WSN influenza virus with low cytotoxicity, while the structure-activity relationships were discussed. Spiromastilactone D (4), a 5'-chloro-2'-methoxy substituted analogue, displayed the most potent to inhibit a panel of influenza A and B viruses in addition to drug-resistant clinical isolates. Mechanistic investigation resulted in that compound 4 bonded to hemagglutinin protein (HA), potentially at the spherical head, and disrupted the HA-sialic acid receptor interaction, that is essential for the attachment and entry of all influenza viruses. In addition, compound 4 also showed inhibitory effect toward viral genome replication via targeting viral RNP complex. The synergistic effects of 4 on both viral entry and replication assumed it to be a promising lead for the development of a new influenza inhibitor. PMID- 26686930 TI - The new facile and straightforward method for the synthesis of 4H-1,2,3 thiadiazolo[5,4-b]indoles and determination of their antiproliferative activity. AB - A series of 4H-1,2,3-thiadiazolo[5,4-b]indoles were synthesized by novel tandem of oxidative cyclization of 3-alkoxycarbonylhydrazonoindoline-2-thiones, 1,5-H shift and elimination of tert-butoxy(ethoxy)carbonyl group. The simple method for their modifications by the reactions with electrophilic agents were elaborated and as a result of the synthetic investigation a number of N-alkyl-, N-acyl- and N-sulfonyl-4H-1,2,3-thiadiazolo[5,4-b]indoles were prepared in good yields. Preliminary biological tests for the three examples of synthesized compounds with different substituents at the nitrogen atom indole ring have shown that the biological behavior of the investigated 1,2,3-thiadiazolo[5,4-b]indoles is substantially directed by this structural fragment. PMID- 26686931 TI - Discovery of indeno[1,2-b]quinoxaline derivatives as potential anticancer agents. AB - We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-{[3-(dimethylamino)propoxy]imino}-N [3-(dimethylamino) propyl]-11H-indeno[1,2-b]quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 MUM (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 MUM. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0 MUM in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 MUM. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10ain vivo. PMID- 26686932 TI - The permuted locus trial--Well suited for emerging pathogens? AB - The recent Ebola virus epidemic was waning by the time stakeholders were ready to field vaccines for testing but an evidence-based response to a novel pathogen will surely be required again. Here, we present a design for such a randomized controlled trial. The permuted locus trial was originally intended for studying the influence of water wells on trachoma. While outcomes can be measured in individuals, neither individuals nor groups are themselves randomized to arms, just potential well-sites, or in the case of an epidemic, index cases. The permuted locus trial may be used when classic individual and cluster-randomized trial design and analyses may not be optimal. PMID- 26686933 TI - Does the absence of gasping upon emergency medical services arrival indicate the need for endotracheal intubation? PMID- 26686934 TI - The impact of a freestanding ED on a regional emergency medical services system. AB - OBJECTIVE: The objective of the study is to examine the effect of the opening of a freestanding emergency department (FED) on the surrounding emergency medical services (EMS) system through an examination of EMS system metrics such as ambulance call volume, ambulance response times, and turnaround times. METHODS: This study is based on data from the county's computer-aided dispatch center, the FED, and the Maryland Health Services Cost Review Commission. The analysis involved a pre/post design, with a 6-month washout period. The preintervention period was April to October 2010, and the postintervention period was April to October 2011. Data were analyzed using standard t tests. RESULTS: The average daily number of EMS-related calls received in the computer-aided dispatch center was lower after the FED opened (16.3 [95% confidence interval {CI}, 15.7-16.9] vs 15.8 [95% CI, 14.9-16.9]). One-fourth of all patients were transported by ambulance to the FED after it opened. Use of the FED and adjacent hospitals increased by 8647 visits (15.8%) during the study period. Turnaround time for the county's ALS units decreased from 26.8 (95% CI, 26.2-27.5) to 25.1 (95% CI, 24.3 25.8) minutes. The ambulance out-of-service interval decreased from 87.3 (95% CI, 86.0-88.5) to 81.1 (95% CI, 79.7-82.4) minutes. Based on change in out-of-service this study had a small effect size (Cohen's d = 0.33). CONCLUSIONS: The opening of an FED was associated with a modest improvement in time-specific EMS system metrics: a decrease in ambulance turnaround time and shorter out-of-service intervals. PMID- 26686935 TI - Diagnostic challenges with stump appendicitis. PMID- 26686936 TI - Integration of point-of-care sonography during rapid sequence intubation in trauma resuscitation: will it make a difference? PMID- 26686937 TI - Celiac sprue presenting as pseudomyocardial infarction. PMID- 26686939 TI - Carbapenem-resistant Klebsiella pneumoniae isolates from Egypt containing blaNDM 1 on IncR plasmids and its association with rmtF. AB - OBJECTIVES: The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates recovered from clinical specimens at a tertiary care hospital in Egypt over a period of 15 months. METHODS: Eight CRKP isolates were included in this study. The minimum inhibitory concentrations of different antibiotics were determined by broth microdilution and Etest methods. Multilocus sequence typing was performed. Antibiotic resistance genes were assessed by PCR and DNA sequencing. Plasmid analysis was done by S1 nuclease digestion of whole genomic DNA followed by pulsed-field gel electrophoresis (S1 PFGE). RESULT: Eight carbapenem-resistant NDM-1-producing K. pneumoniae isolates of three different sequence types (ST) were identified (ST147, ST11, and ST17), in which blaNDM-1 was carried by either IncR or untypeable plasmids. Seven out of the eight isolates also contained the rmtF methylase gene. CONCLUSION: This study describes the occurrence of IncR plasmids carrying blaNDM-1 and rmtF in Egypt, raising concerns regarding this type of replicon and its role in the transmission of these resistance determinants. PMID- 26686938 TI - A method for rapid detection and genotype identification of hepatitis C virus 1-6 by one-step reverse transcription loop-mediated isothermal amplification. AB - OBJECTIVE: Hepatitis C virus (HCV) is probably the leading cause of liver cirrhosis and hepatocellular carcinoma globally. Diagnostic tools conventionally used for the detection and identification of HCV infection are technically demanding, time-consuming, and costly for resource-limited environments. This study reports the development of the first rapid loop-mediated reverse transcription isothermal amplification assay that rapidly detects and identifies HCV genotypes in blood components. METHODS: RNA extracted from donor plasma and serum specimens was applied to a one-step reverse transcription loop-mediated isothermal amplification reaction performed with HCV-specific oligonucleotides. Reactions were conducted at 63.5 degrees C for 30-60 min. The diagnostic characteristics of the assay were investigated and validated with clinical specimens. RESULTS: Electrophoretic analysis of amplification revealed detection and identification of HCV genotypes 1-6. Positive amplification revealed unique ladder-like banding patterns that identified each HCV genotype. The assay demonstrated a sensitivity of 91.5% and specificity of 100%. Rapid naked-eye detection of HCV infection was facilitated by observation of an intense fluorescent glow of amplified targets under UV illumination. CONCLUSION: These diagnostic characteristics highlight the potential utility of this assay for the rapid detection and genotype identification of HCV infection in field and point of-care settings in endemic regions and resource-limited environments. PMID- 26686941 TI - Cost-effectiveness of culture-guided antimicrobial prophylaxis for the prevention of infections after prostate biopsy. AB - BACKGROUND: Clinical findings suggest that the use of rectal culture-guided antibiotic prophylaxis reduces the infection rate following transrectal ultrasound-guided prostate biopsy (TRUSBx). METHODS: A decision-analytic model was designed to compare the outcomes of TRUSBx performed with (rectal culture guided group) and without (standard ciprofloxacin prophylaxis) rectal swab culture-guided antimicrobial prophylaxis in Hong Kong. The post-biopsy infection rate, infection-related costs, quality-adjusted life years (QALYs) lost for infection, and incremental cost per QALY saved (ICER) were assessed. Model inputs were retrieved from local epidemiology data and the medical literature. A sensitivity analysis was performed to test the robustness of the model results. RESULTS: Base-case analysis showed that the infection rate in the culture-guided group was reduced from 2.42% to 0.23% and saved 0.0002 QALYs, with a lower cost (USD 31.4 versus USD 55.6) (USD 1=HKD 7.8). The number needed to screen to prevent an infection episode was 45.7. The hospital days avoided per 100 patients using culture-guided prophylaxis was 7.08 days. The relative effectiveness of culture-guided antimicrobial prophylaxis versus standard prophylaxis in carriers and non-carriers of FQ-resistant rectal flora were identified as potential influencing factors. In 10000 Monte Carlo simulations, ICERs of the culture guided group were below the willingness-to-pay threshold 99.12% of the time. CONCLUSIONS: Using rectal culture-guided antimicrobial prophylaxis for men undergoing TRUSBx appears to be a cost-saving strategy to avert post-biopsy infection and QALY loss in Hong Kong. PMID- 26686940 TI - Antimicrobial susceptibility and emerging resistance determinants (blaCTX-M, rmtB, fosA3) in clinical isolates from urinary tract infections in the Bolivian Chaco. AB - BACKGROUND: Bolivia is among the lowest-resourced South American countries, with very few data available on antibiotic resistance in bacterial pathogens. The phenotypic and molecular characterization of bacterial isolates responsible for urinary tract infections (UTIs) in the Bolivian Chaco are reported here. METHODS: All clinical isolates from UTIs collected in the Hospital Basico Villa Montes between June 2010 and January 2014 were analyzed (N=213). Characterization included susceptibility testing, extended-spectrum beta-lactamase (ESBL) detection, identification of relevant resistance determinants (e.g., CTX-M-type ESBLs, 16S rRNA methyltransferases, glutathione S-transferases), and genotyping of CTX-M producers. RESULTS: Very high resistance rates were observed. Overall, the lowest susceptibility was observed for trimethoprim-sulphamethoxazole, tetracycline, nalidixic acid, amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin. Of E. coli and K. pneumoniae, 11.6% were ESBL producers. Resistance to nitrofurantoin, amikacin, and fosfomycin remained low, and susceptibility to carbapenems was fully preserved. CTX-M-15 was the dominant CTX-M variant. Four E. coli ST131 (two being H30-Rx) were identified. Of note, isolates harbouring rmtB and fosA3 were detected. CONCLUSIONS: Bolivia is not an exception to the very high resistance burden affecting many South American countries. Optimization of alternative approaches to monitor local antibiotic resistance trends in resource limited settings is strongly encouraged to support the implementation of effective empiric treatment guidelines. PMID- 26686942 TI - High levels of anti-tuberculin (IgG) antibodies correlate with the blocking of T cell proliferation in individuals with high exposure to Mycobacterium tuberculosis. AB - OBJECTIVES: To determine the effect of anti-tuberculin antibodies in the T-cell proliferation in response to tuberculin and Candida antigens in individuals with different levels of tuberculosis (TB) risk. METHODS: Sixteen high-risk TB individuals, 30 with an intermediate TB risk (group A), and 45 with a low TB risk (group B), as well as 49 control individuals, were studied. Tuberculin skin test (TST) results were analyzed and serum levels of antibodies (IgG and IgM) against purified protein derivative (PPD) were measured by ELISA. Tuberculin and Candida antigens were used to stimulate T-cell proliferation in the presence of human AB serum or autologous serum. RESULTS: High levels of anti-tuberculin IgG antibodies were found to be significantly associated with the blocking of T-cell proliferation responses in cultures stimulated with tuberculin but not with Candida antigens in the presence of autologous serum. This phenomenon was particularly frequent in high-risk individuals with high levels of anti tuberculin IgG antibodies in the autologous serum when compared to the other risk groups, which exhibited lower levels of anti-tuberculin antibodies. CONCLUSIONS: Although cellular immunity plays a central role in the protection against TB, humoral immunity is critical in the control of Mycobacterium tuberculosis infection in high-risk individuals with latent TB infection. PMID- 26686943 TI - Eastern South African hydroclimate over the past 270,000 years. AB - Processes that control the hydrological balance in eastern South Africa on orbital to millennial timescales remain poorly understood because proxy records documenting its variability at high resolution are scarce. In this work, we present a detailed 270,000 year-long record of terrestrial climate variability in the KwaZulu-Natal province based on elemental ratios of Fe/K from the southwest Indian Ocean, derived from X-ray fluorescence core scanning. Eastern South African climate variability on these time scales reflects both the long-term effect of regional insolation changes driven by orbital precession and the effects associated with high-latitude abrupt climate forcing over the past two glacial-interglacial cycles, including millennial-scale events not previously identified. Rapid changes towards more humid conditions in eastern South Africa as the Northern Hemisphere entered phases of extreme cooling were potentially driven by a combination of warming in the Agulhas Current and shifts of the subtropical anticyclones. These climate oscillations appear coherent with other Southern Hemisphere records but are anti-phased with respect to the East Asian Monsoon. Numerical modelling results reveal that higher precipitation in the KwaZulu-Natal province during precession maxima is driven by a combination of increased local evaporation and elevated moisture transport into eastern South Africa from the coast of Mozambique. PMID- 26686944 TI - Utility of Exposure-Response Analysis in Regulatory Decision on the Selection of Starting Dose of Pasireotide for Cushing Disease. PMID- 26686945 TI - Single nucleotide polymorphisms in the vitamin D pathway associating with circulating concentrations of vitamin D metabolites and non-skeletal health outcomes: Review of genetic association studies. AB - Polymorphisms in genes encoding proteins involved in vitamin D metabolism and transport are recognised to influence vitamin D status. Syntheses of genetic association studies linking these variants to non-skeletal health outcomes are lacking. We therefore conducted a literature review to identify reports of statistically significant associations between single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DHCR7, CYP2R1, CYP3A4, CYP27A1, DBP, LRP2, CUB, CYP27B1, CYP24A1, VDR and RXRA) and non-bone health outcomes and circulating levels of 25-hydroxyvitamin D (25[OH]D and 1,25-dihydroxyvitamin D (1,25[OH]2D). A total of 120 genetic association studies reported positive associations, of which 44 investigated determinants of circulating 25(OH)D and/or 1,25(OH)2D concentrations, and 76 investigated determinants of non-skeletal health outcomes. Statistically significant associations were reported for a total of 55 SNP in the 11 genes investigated. There was limited overlap between genetic determinants of vitamin D status and those associated with non-skeletal health outcomes: polymorphisms in DBP, CYP2R1 and DHCR7 were the most frequent to be reported to associate with circulating concentrations of 25(OH)D, while polymorphisms in VDR were most commonly reported to associate with non-skeletal health outcomes, among which infectious and autoimmune diseases were the most represented. PMID- 26686946 TI - MEG as a Medical Diagnostic Tool in the Greek Population. AB - Magnetoencephalography (MEG) is the recording of the magnetic field produced by the flowing of ions in the brain. This article reports our experience in the application of MEG in patients and healthy volunteers in the Greek population. We provide a brief description of our research work. The MEG data were recorded in a magnetically shielded room with a whole-head 122 channel or an one-channel biomagnetometer. Our results lead us to believe that the MEG is an important research field which is evolving quickly with a number of interesting findings with respect to normal and abnormal functions of the human brain. It could provide clinical practice with an easy to perform non invasive method, which could be adjunct to conventional methods for the evaluation of brain disorders. PMID- 26686947 TI - Cell Stratification, Spheroid Formation and Bioscaffolds Used to Grow Cells in Three Dimensional Cultures. AB - The cell culture became an invaluable tool for studying cell behaviour, development, function, gene expression, toxicity of compounds and efficacy of novel drugs. Although most results were obtained from cell cultivation in two dimensional (2D) systems, in which cells are grown in a monolayer, three dimensional (3D) cultures are more promising as they correspond closely to the native arrangement of cells in living tissues. In our study, we focused on three types of 3D in vitro systems used for cultivation of one cell type. Cell morphology, their spatial distribution inside of resulting multicellular structures and changes in time were analysed with histological examination of samples harvested at different time periods. In multilayered cultures of WRL 68 hepatocytes grown on semipermeable membranes and non-passaged neurospheres generated by proliferation of neural progenitor cells, the cells were tightly apposed, showed features of cell differentiation but also cell death that was observable in short-term cultures. Biogenic scaffolds composed of extracellular matrix of the murine tibial anterior muscle were colonized with C2C12 myoblasts in vitro. The recellularized scaffolds did not reach high cell densities comparable with the former systems but supported well cell anchorage and migration without any signs of cell regression. PMID- 26686949 TI - Non-Invasive Ocular Rigidity Measurement: A Differential Tonometry Approach. AB - PURPOSE: Taking into account the fact that Goldmann applanation tonometry (GAT) geometrically deforms the corneal apex and displaces volume from the anterior segment whereas Dynamic Contour Tonometry (DCT) does not, we aimed at developing an algorithm for the calculation of ocular rigidity (OR) based on the differences in pressure and volume between deformed and non-deformed status according to the general Friedenwald principle of differential tonometry. METHODS: To avoid deviations of GAT IOP from true IOP in eyes with corneas different from the "calibration cornea" we applied the previously described Orssengo-Pye algorithm to calculate an error coefficient "C/B". To test the feasibility of the proposed model, we calculated the OR coefficient (r) in 17 cataract surgery candidates (9 males and 8 females). RESULTS: The calculated r according to our model (mean +/- SD, range) was 0.0174 +/- 0.010 (0.0123-0.022) mmHg/MUL. A negative statistically significant correlation between axial length and r was detected whereas correlations between r and other biometric parameters examined were statistically not significant. CONCLUSIONS: The proposed method may prove a valid non-invasive tool for the measurement method of OR, which could help in introducing OR in the decision-making of the routine clinical practice. PMID- 26686948 TI - Deep Neck infections of Odontogenic Origin and Their Clinical Significance. A Retrospective Study from Hradec Kralove, Czech Republic. AB - INTRODUCTION: Cellulitis remains a very serious disease even today. Mortality, which varied between 10-40%, has been reduced owing to the standard securing of airway patency and use of an appropriate surgical treatment approach. MATERIALS AND METHODS: A total of 195 patients were hospitalised for cellulitis at the University Hospital in Hradec Kralove during 2007-2011. The following parameters were evaluated: age, gender, dependence of incidence of the disease on the season of the year, frequency of attacks of the particular areas and their clinical characteristics, aetiology of the inflammation, types of patient complaints, prevalence of current systemic diseases, results of microbiological and selected laboratory analyses, socio-economic status of the patients, and duration of patient stay at the hospital. Statistical analysis was performed by using Pearson's correlation coefficient, the statistical significance level was p < 0.05. RESULTS: The mean age of the patients was 39.8 years. The group of 195 patients included 108 (55%) males and 87 (45%) females. The mean time between the first symptoms of the disease and admission to the Department was 5 days. From among the 195 patients, 116 (59.5%) were working persons, 79 (40.5%) were non working (children, students, unemployed persons, women on maternity leave, retired people). The odontogenic origin of the disease was verified in 173 (88.7%) patients. In total, 65 (33.3%) patients had no coinciding complicating systemic disease, 22 (11.3%) patients had diabetes mellitus. The most frequent symptom of cellulitis was painful swelling, found in 194 (99.5%) patients, followed by jaw contracture, found in 153 (78.5%) patients. CONCLUSION: The results are largely very similar to those of previous studies performed in other countries, except that we found no correlation between the prevalence of cellulitis and the socio-economic status, nor have we confirmed Klebsiella pneumoniae sp. as the cause of cellulitis in patients with diabetes mellitus. PMID- 26686950 TI - Osteochondritis Dissecans of the Knee in Children and Adolescents: Our Experience with Transchondral Drilling. AB - Osteochondritis dissecans(OCD) of the knee is identified with increasing frequency in the adolescent patient. Left untreated, OCD can cause significant impairment and restriction in physical activity and development of osteoarthritis at an early age. The diagnosis of lesions of OCD can be confirmed on plain radiographs. MRI has emerged as the gold standard to evaluate the stability of the lesion and the integrity of the overlying articular cartilage. Treatment of OCD lesions depend on the stability of the lesion. Stable lesions can be treated conservatively by physical activity modification and immobilization. Unstable lesions and stable lesions not responding to conservative measures should be treated surgically. Surgical options range from arthroscopic drilling, either transarticular or extra-articular drilling for stable lesions or salvage procedures such as autologous chondrocyte transplantation (ACT), mosaicplasty to restore joint and cartilage congruency. PMID- 26686951 TI - Needs of Hospitalized Schizophrenic Patients in the North Moravia and the Czech Part of Silesia. AB - OBJECTIVES: The main aim of the study was to investigate the physiological and social needs of patients hospitalized with schizophrenia to uncover potential issues in these areas. METHODS: The relevant self-evaluating CANSAS questionnaire for physiological and social needs was used by nurses in a cohort of hospitalized schizophrenic patients undergoing rehabilitation before discharge from the mental hospital. RESULTS: Two hundred and forty-four patients (women N = 115) aged 18-58 years were involved in the study. Intimate relations, financial matters, treatment of psychotic symptoms, and sexual life were among the most pressing physiological and social needs in our study subjects. CONCLUSION: The results of our study should stimulate psychiatric nurses in their effort not only to detect but also address the problems of schizophrenic patients concerning unfulfilled needs. PMID- 26686952 TI - Encephalitis with Prolonged but Reversible Splenial Lesion. AB - INTRODUCTION: The splenium of the corpus callosum has a specific structure of blood supply with a tendency towards blood-brain barrier breakdown, intramyelinic edema, and damage due to hypoxia or toxins. Signs and symptoms of reversible syndrome of the splenium of the corpus callosum typically include disorientation, confusion, impaired consciousness, and epileptic seizures. CASE REPORT: A previously healthy 32-year-old man suffered from weakness, headache, and fever. Subsequently, he developed apathy, ataxia, and inability to walk, and therefore was admitted to the hospital. Cerebrospinal fluid showed protein elevation (0.9 g/l) and pleocytosis (232/1 ul). A brain MRI showed hyperintense lesions in the middle of the corpus callosum. The patient was treated with antibiotics, and subsequently, in combination with steroids. Two months later, the hyperintense lesions in the splenium and the basal ganglia had disappeared. Almost seven months since his hospitalization in the Department of Neurology, the patient has returned to his previous employment. He now does not exhibit any mental changes, an optic edema and urological problems have improved. In addition, he is now actively engaged in sports. CONCLUSION: We have described a case of a 32-year-old man with confusion, ataxia, and inability to stand and walk. The man developed a febrile meningeal syndrome and a hyperintense lesion of the splenium, which lasted for two months. Neurological changes, optic nerve edema, and urinary retention have resolved over the course of seven months. We think that the prolonged but transient lesion of the splenium may have been caused by encephalitis of viral origin. PMID- 26686953 TI - [Environmental decontamination has reached the patient]. PMID- 26686954 TI - Adenoid cystic carcinoma of the minor salivary glands: a retrospective series of 29 cases and review of the literature. AB - OBJECTIVE: Approximately 78% of minor salivary gland tumors are malignant, of which adenoid cystic carcinoma (ACC) represents 15% in our series. ACC is an uncommon tumor characterized by slow growth and a high potential for recurrence. This series of 29 consecutive patients examines clincopathologic features, management, and survival outcomes. MATERIALS AND METHODS: This study is a retrospective chart review of 29 patients with ACC of the minor salivary glands in a period of 23 years (1989 and 2012). RESULTS: The mean age was 61.2 years (16 89 years), with no gender predilection. The majority occurred in the palate/maxilla (66%) and initial presentation was stage IV. Mean follow-up was 42.6 months. Recurrence rate was 10% local, 14% distant over the observation period. CONCLUSIONS: The palate/maxilla is the preferred location for occurrence, and initial presentation at stage IV is common. Postoperative radiation remains a common strategy to prevent local recurrence in lesions with adverse features. PMID- 26686955 TI - Restricted mouth opening in chronic graft-versus-host disease. PMID- 26686956 TI - Protumorigenic M2-like phenotype cell infiltration in the melanotic neuroectodermal tumor of infancy. AB - OBJECTIVE: The aim of this study is to report 2 cases of melanotic neuroectodermal tumor of infancy (MNTI), emphasizing the analysis of intratumoral immune cells by immunohistochemistry. STUDY DESIGN: Case 1: A 6-month-old girl presented with a 3-cm tumor in the anterior region of the left maxilla. Case 2: A 4-month-old boy presented with a 4-cm tumor in the anterior region of the left maxilla. Microscopically, case 1 had predominantly neuroblast-like cells supported by fibrillary neuropil-like stroma arranged in an alveolar pattern, whereas case 2 exhibited scattered melanocyte-like and neuroblast-like cells supported by fibrovascular stroma. A large immunohistochemical panel for characterizing intratumoral macrophage and dendritic cell subsets was performed. RESULTS: Immunohistochemical analysis indicated positivity for HLA-DR, XIIIa, CD68, and CD163 (range 6%-50%) mainly on the fibrovascular stroma, suggesting M2 macrophage-like cell phenotype. CD138 was overexpressed in the tumor stroma. CONCLUSIONS: Results suggest the involvement of M2-polarized macrophages in the MNTI pathogenesis, which may act by modulating tumor growth and/or tumor stromal remodeling. PMID- 26686958 TI - Pott's disease in a Connecticut toddler. PMID- 26686957 TI - Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double blind, phase 3 clinical trial. AB - BACKGROUND: Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy. METHODS: The double-blind, randomised, phase 3 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 trial was done in 333 participating NSABP centres in the USA and Canada. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole-breast irradiation were enrolled and randomly assigned (1:1) to receive either oral tamoxifen 20 mg per day (with matching placebo in place of anastrozole) or oral anastrozole 1 mg per day (with matching placebo in place of tamoxifen) for 5 years. Randomisation was stratified by age (<60 vs >=60 years) and patients and investigators were masked to treatment allocation. The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00053898, and is complete. FINDINGS: Between Jan 1, 2003, and June 15, 2006, 3104 eligible patients were enrolled and randomly assigned to the two treatment groups (1552 to tamoxifen and 1552 to anastrozole). As of Feb 28, 2015, follow-up information was available for 3083 patients for overall survival and 3077 for all other disease-free endpoints, with median follow-up of 9.0 years (IQR 8.2-10.0). In total, 212 breast cancer free interval events occurred: 122 in the tamoxifen group and 90 in the anastrozole group (HR 0.73 [95% CI 0.56-0.96], p=0.0234). A significant time-by treatment interaction (p=0.0410) became evident later in the study. There was also a significant interaction between treatment and age group (p=0.0379), showing that anastrozole is superior only in women younger than 60 years of age. Adverse events did not differ between the groups, except for thrombosis or embolism--a known side-effect of tamoxifen-for which there were 17 grade 4 or worse events in the tamoxifen group versus four in the anastrozole group. INTERPRETATION: Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ. FUNDING: US National Cancer Institute and AstraZeneca Pharmaceuticals LP. PMID- 26686959 TI - Health benefits of a carbon tax. PMID- 26686961 TI - Associations of Different Adipose Tissue Depots with Insulin Resistance: A Systematic Review and Meta-analysis of Observational Studies. AB - Fat distribution is strongly associated with insulin resistance, a risk factor for type 2 diabetes and cardiovascular diseases. However, associations of different adipose tissue depots or/and obesity indices with insulin resistance have not been systematically evaluated. In this study we examined associations of different adipose tissue depots/obesity indices with insulin resistance, as measured by homeostatic model assessment of insulin resistance (HOMA-IR) in observational studies. A total of 40 studies with 56 populations and 29 adipose tissue depots/obesity indices were included in the meta-analysis. There were strong correlation between HOMA-IR and visceral fat mass (r = 0.570, 95% confidence interval(CI): 0.424~0.687), total fat mass (r = 0.492, 95%CI: 0.407~0.570), body mass index (r = 0.482, 95%CI: 0.445~0.518) and waist circumference (r = 0.466, 95%CI: 0.432~0.500), except lower extremity fat (r = 0.088, 95%CI: -0.116~0.285). Sample size, diabetic status, gender, mean of body mass index, and race contributed to heterogeneity of these associations. This study showed a positive correlation between insulin resistance and most adipose tissue depots/obesity indices, and the strongest association is for visceral fat mass. PMID- 26686960 TI - Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. AB - BACKGROUND: The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms. METHODS: The study was done at 333 hospitals in North America. Postmenopausal women with hormone positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were randomly assigned to receive either tamoxifen (20 mg/day) or anastrazole (1 mg/day) for 5 years, stratified by age (<60 years vs >=60 years). Patients and investigators were masked to treatment allocation. Patients completed questionnaires at baseline and every 6 months thereafter for 6 years. The primary outcomes were SF-12 physical and mental health component scale scores, and vasomotor symptoms (as per the BCPT symptom scale). Secondary outcomes were vaginal symptoms and sexual functioning. Exploratory outcomes were musculoskeletal pain, bladder symptoms, gynaecological symptoms, cognitive symptoms, weight problems, vitality, and depression. We did the analyses by intention to treat, including patients who completed questionnaires at baseline and at least once during follow-up. This study is registered with ClinicalTrials.gov, NCT00053898. FINDINGS: Between Jan 6, 2003, and June 15, 2006, 3104 patients were enrolled in the study, of whom 1193 were included in the quality-of-life substudy: 601 assigned to tamoxifen and 592 assigned to anastrozole. We detected no significant difference between treatment groups for: physical health scores (mean severity score 46.72 for tamoxifen vs 45.85 for anastrozole; p=0.20), mental health scores (52.38 vs 51.48; p=0.38), energy and fatigue (58.34 vs 57.54; p=0.86), or symptoms of depression (6.19 vs 6.39; p=0.46) over 5 years. Vasomotor symptoms (1.33 vs 1.17; p=0.011), difficulty with bladder control (0.96 vs 0.80; p=0.0002), and gynaecological symptoms (0.29 vs 0.18; p<0.0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1.50 vs 1.72; p=0.0006) and vaginal symptoms (0.76 vs 0.86; p=0.035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43.65 vs 45.29; p=0.56). Younger age was significantly associated with more severe vasomotor symptoms (mean severity score 1.45 for age <60 years vs 0.65 for age >=60 years; p=0.0006), vaginal symptoms (0.98 vs 0.65; p<0.0001), weight problems (1.32 vs 1.02; p<0.0001), and gynaecological symptoms (0.26 vs 0.22; p=0.014). INTERPRETATION: Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug. For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative. FUNDING: US National Cancer Institute, AstraZeneca Pharmaceuticals. PMID- 26686962 TI - Dendritiform Keratopathy Associated with Exposure to Polyquarternium-1, a Common Ophthalmic Preservative. AB - PURPOSE: To describe dendritiform keratopathy associated with exposure to polyquaternium-1, a common preservative found in contact lens solutions and tear replacement products. DESIGN: Case series. PARTICIPANTS: Sixteen patients who demonstrated dendritiform keratopathy during topical ophthalmic exposure to polyquaternium-1. METHODS: Records were reviewed of all patients diagnosed with dendritiform keratopathy between 1999 and 2014 who had documented exposure to contact lens care disinfecting solutions or artificial tear solutions containing polyquaternium-1. Patients were excluded who had coexisting potential causes for dendritiform keratopathy, such as prior herpes simplex keratitis, varicella zoster viral keratitis, the linear form of Thygeson's superficial keratitis, epithelial regeneration line, Acanthamoeba keratitis, mucus plaque keratopathy, medication-related keratopathy, or limbal stem cell deficiency characterized by conjunctivalization of the corneal epithelium. MAIN OUTCOME MEASURES: Effect of discontinuation of exposure to polyquaternium-1 on the dendritiform keratopathy. RESULTS: Sixteen patients demonstrated dendritiform keratopathy after exposure to the preservative polyquaternium-1. Thirteen patients had a history of recent exposure to contact lens disinfecting solutions (Opti-Free, Equate) containing polyquaternium-1. Three patients used a tear replacement product (Systane) containing a polyquaternium-1 preservative. Four patients were treated with antiviral medications for presumed herpes simplex keratitis; 4 patients underwent diagnostic testing for Acanthamoeba keratitis. Two additional patients were diagnosed sequentially with herpes simplex keratitis, then Acanthamoeba keratitis before referral. All dendritiform lesions resolved within 2 to 6 weeks after elimination of exposure to polyquaternium-1. CONCLUSIONS: Ophthalmic products containing polyquaternium-1 may cause dendritiform keratopathy that may be confused with infections of the superficial cornea, such as herpes simplex virus keratitis or Acanthamoeba keratitis. PMID- 26686963 TI - Association between Eye Shape and Myopic Traction Maculopathy in High Myopia. PMID- 26686965 TI - Surgical versus Medical Treatment of Ocular Surface Squamous Neoplasia: A Cost Comparison. AB - PURPOSE: The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNalpha2b) treatment for ocular surface squamous neoplasia (OSSN). DESIGN: A matched, case-control study. PARTICIPANTS: A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically. METHODS: Patients with OSSN treated with IFNalpha2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis. MAIN OUTCOME MEASURES: Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges. RESULTS: When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNalpha2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections). CONCLUSIONS: Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage. PMID- 26686964 TI - Risk of Retinal Neovascularization in Cases of Uveitis. AB - PURPOSE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13,810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26,465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27 0.41). Factors associated with incident NV include age <35 years compared with >35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed >5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within <1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection. PMID- 26686967 TI - Subfoveal Choroidal Thickness during Aflibercept Therapy for Neovascular Age Related Macular Degeneration: Twelve-Month Results. AB - PURPOSE: To investigate changes in subfoveal choroidal thickness after intravitreal aflibercept injections (IAIs) for neovascular age-related macular degeneration (AMD) at 12 months. DESIGN: Retrospective, consecutive, interventional case series. PARTICIPANTS: One hundred forty-four patients with treatment-naive neovascular AMD examined at 3 university hospitals. METHODS: After a loading phase of 3 monthly 2.0-mg IAIs, the patients were injected bimonthly with additional rescue injections performed for worsening. Subfoveal choroidal thickness in IAI-treated eyes was evaluated using enhanced depth imaging optical coherence tomography (OCT) or swept-source OCT. MAIN OUTCOME MEASURES: Changes in subfoveal choroidal thickness over a 12-month period. RESULTS: Of the 144 treated eyes, 58 (40.3%) had typical neovascular AMD and 86 (59.7%) had polypoidal choroidal vasculopathy (PCV). The mean subfoveal choroidal thickness of treated eyes decreased from 268.1+/-101.3 MUm at baseline to 233.0+/ 99.7 MUm at 3 months and remained unchanged at 232.4+/-99.6 MUm at 12 months (percentage decrease, 13.3% at 12 months compared with baseline; P < 0.0001), although there was some fluctuation in between treatments. This decrease in subfoveal choroidal thickness was associated significantly with gain in visual acuity for PCV eyes (P = 0.0087; R = 0.28), but not for eyes with typical neovascular AMD (P = 0.17; R = 0.18). Eyes without persistent or recurrent retinal fluid after the loading phase showed greater decrease in subfoveal choroidal thickness compared with those with persistent or recurrent retinal fluid, in both typical neovascular AMD (P = 0.042) and PCV (P = 0.038) eyes. CONCLUSIONS: Subfoveal choroidal thickness decreased over 12 months with IAI therapy in eyes with neovascular AMD. Changes in subfoveal choroidal thickness after IAIs seem to be related to visual and anatomic outcomes. PMID- 26686968 TI - Adjuvant Role of Amniotic Membrane Transplantation in Acute Ocular Stevens Johnson Syndrome: A Randomized Control Trial. AB - PURPOSE: To evaluate the adjuvant role of amniotic membrane transplantation (AMT) in cases of acute ocular Stevens-Johnson syndrome (SJS). DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: Twenty-five patients (50 eyes) with acute ocular SJS who presented within 4 weeks of onset of symptoms were recruited. METHODS: The eyes were randomized into 2 groups that underwent either AMT with medical therapy (MT; n = 25) or standard MT alone (n = 25). The patients were evaluated at presentation and during follow-up at 1 week and 1, 3, and 6 months. The parameters evaluated were the best-corrected visual acuity (BCVA), Schirmer test, tear film breakup time (TBUT), conjunctival congestion, corneal haze, vascularization, conjunctivalization, and limbal stem cell involvement. Lid edema, symblepharon, ankyloblepharon, ectropion, entropion, trichiasis, and metaplastic lashes also were analyzed. MAIN OUTCOME MEASURES: Maintenance of BCVA and stable ocular surface. RESULTS: At the end of 6 months, the mean BCVA was significantly better in the AMT group (0.068+/-0.10 logMAR units) compared with the MT group (0.522+/-0.52 logMAR units; P = 0.042). The mean TBUT in the AMT and MT groups was 9.92+/-4.1 and 6.96+/-4.5 seconds, respectively (P = 0.015). The mean Schirmer test results in the AMT and MT groups were 15.4+/-6.3 and 8.64+/-5.4 mm, respectively (P < 0.001). Conjunctival congestion persisted in 44% (11/25) in the MT group compared with 4% (1/25) in the AMT group (P = 0.03) at the end of the 6-month follow-up. No case in the AMT group demonstrated corneal haze, limbal stem cell deficiency, symblepharon, ankyloblepharon, or lid-related complications. Among eyes in the MT group, corneal haze occurred in 44% (11/25; P = 0.001), corneal vascularization and conjunctivalization in 24% (6/25; P = 0.03), symblepharon in 16% (4/25; P = 0.12), ankyloblepharon in 4% (1/25; P = 1.00), ectropion and entropion in 8% (2/25; P = 0.47), and trichiasis and metaplastic lashes in 24% (6/25; P = 0.03) eyes. CONCLUSIONS: Amniotic membrane transplantation is a useful adjunct to conventional MT in maintaining BCVA and a stable ocular surface in cases of acute ocular SJS. Furthermore, the adjunctive use of AMT also helps to prevent intermediate-term ocular cicatricial sequelae. PMID- 26686969 TI - Contact Lens-Assisted Pull-Through Technique for Delivery of Tri-Folded (Endothelium in) DMEK Grafts Minimizes Surgical Time and Cell Loss. AB - PURPOSE: To evaluate the feasibility and outcomes of contact lens-assisted bimanual pull-through delivery of Descemet membrane endothelial keratoplasty (DMEK) tissue trifolded with the endothelium inward. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Forty-two consecutive eyes of 42 patients with Fuchs endothelial dystrophy with or without cataract. INTERVENTION: Standardized DMEK was performed as a single procedure (n = 9) or in combination with phacoemulsification and implantation of a posterior chamber intraocular lens (n = 33) using prestripped donor tissue punched to a diameter of 8.25 mm and then trifolded with the endothelium in. Using a sterile soft contact lens as scaffold, the tissue was loaded in this configuration into a disposable cartridge and delivered into the anterior chamber under continuous irrigation using a bimanual pull-through technique to facilitate spontaneous proper unfolding. MAIN OUTCOME MEASURES: Surgical time, intraoperative and postoperative complications, visual acuity 3 and 6 months after surgery, and endothelial cell loss 6 months after surgery. RESULTS: Surgery was uneventful in all cases and the time required for the DMEK procedure (from Descemet scoring until final air filling) never exceeded 20 minutes (average, 17.1+/-1.6 minutes). The only complication observed after surgery was graft detachment (10 of 42 eyes [23.8%]), successfully managed in all cases by single rebubbling within 6 days from surgery. In all eyes with a minimum postoperative follow-up of 6 months (n = 20), best spectacle-corrected visual acuity was 20/25 or better and the average endothelial cell density (+/-standard deviation) was 2363.8+/-82.7 cells/mm(2) (range, 2258-2490 cells/mm(2)). The cell loss calculated as a percentage of the preoperative value determined at the eye bank (range, 2500-2700 cells/mm(2)) was 9.9+/-2.1% (range, 4.1%-11.9%). CONCLUSIONS: Delivering DMEK tissue, trifolded with the endothelium inward, reduces surgical trauma to donor cells and facilitates spontaneous unfolding, thus minimizing surgical time. PMID- 26686970 TI - Clinical events and their relation to the tumor necrosis factor-alpha and interleukin-10 genotypes in Sickle-Cell-Anemia patients. AB - OBJECTIVE/BACKGROUND: Sickle-cell anemia (SCA) is a genetic blood disease characterized by chronic inflammation and a heterogeneous clinical picture. Serum tumor necrosis factor (TNF-alpha) and interleukin 10 (IL-10) levels are associated with the clinical course of SCA. This study aimed to evaluate the association between the frequency of the polymorphisms TNF-alpha-308 G->A, IL-10 1082 G->A, IL-10-819 C->T, and IL-10-592 A->C; serum TNF-alpha; and IL-10 levels, and the incidence of clinical events in SCA patients. METHODS: Polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay were performed on 25 adults with SCA at the steady state; their data were compared with those for 26 healthy individuals. RESULTS: The most frequent genotype of the TNF-alpha polymorphism was GG (low producer), and the most frequent genotype of the IL-10 polymorphisms was "low producer" (ACC ACC, ACC ATA, ATA ATA). The TNF-alpha levels were significantly higher in SCA in patients with acute chest syndrome (ACS). The IL-10 levels were reduced in polytransfusion and in patients with ACS. CONCLUSION: The patients presented prevalence of TNF alpha and IL-10 low-profile producer. The cytokine serum levels presented an association with the presence of polytransfusion and ACS in SCA patients. PMID- 26686972 TI - Experiments and theory of 138La radioactive decay. AB - We measured with unprecedented accuracy key features of the (138)La radioactive decays as beta particle energy distribution from 0.5 keV to the end-point and ratios of electron capture probabilities PL/PK, PM/PK and PM/PL. This was achieved by making use of LaBr3:Ce and CeBr3 scintillator detectors. The advantage of the presented technique relies on the double role of LaBr3:Ce as source of (138)La and detector medium resulting in a relatively efficient counting statistics and unaltered beta energy detection. The experimental results are compared to advanced computational techniques and significant deviation is found below 20 keV with the computational spectrum showing a 5% excess of beta particle relative to the experimental spectrum at 10 keV. PMID- 26686971 TI - Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma. AB - There is an urgent need for improved therapies for children with high-risk neuroblastoma where survival rates remain low. MYCN amplification is the most common genomic change associated with aggressive neuroblastoma and drugs targeting PI3K/AKT/mTOR, to activate MYCN oncoprotein degradation, are entering clinical evaluation. Our aim was to develop and validate pharmacodynamic (PD) biomarkers to evaluate both proof of mechanism and proof of concept for drugs that block PI3K/AKT/mTOR pathway activity in children with neuroblastoma. We have addressed the issue of limited access to tumor biopsies for quantitative detection of protein biomarkers by optimizing a three-color fluorescence activated cell sorting (FACS) method to purify CD45-/GD2+/CD56+ neuroblastoma cells from bone marrow. We then developed a novel quantitative measurement of MYCN protein in these isolated neuroblastoma cells, providing the potential to demonstrate proof of concept for drugs that inhibit PI3K/AKT/mTOR signaling in this disease. In addition we have established quantitative detection of three biomarkers for AKT pathway activity (phosphorylated and total AKT, GSK3beta and P70S6K) in surrogate platelet-rich plasma (PRP) from pediatric patients. Together our new approach to neuroblastoma cell isolation for protein detection and suite of PD assays provides for the first time the opportunity for robust, quantitative measurement of protein-based PD biomarkers in this pediatric patient population. These will be ideal tools to support clinical evaluation of PI3K/AKT/mTOR pathway drugs and their ability to target MYCN oncoprotein in upcoming clinical trials in neuroblastoma. PMID- 26686973 TI - MDV3100: Tritium labeling at high specific activity. AB - An efficient method is described to tritiate MDV3100 at high specific activity. PMID- 26686974 TI - Evaluation of nuclear reaction cross sections for optimization of production of the emerging diagnostic radionuclide 55Co. AB - The excitation functions of the (54)Fe(d,n)(55)Co, (56)Fe(p,2n)(55)Co and (58)Ni(p,alpha)(55)Co reactions were analyzed with relevance to the production of the beta(+)-emitter (55)Co (T1/2=17.53 h), a promising cobalt radionuclide for PET imaging. The nuclear model codes ALICE-IPPE, EMPIRE and TALYS were used to check the consistency of the experimental data. The statistically fitted excitation function was employed to calculate the integral yield of the product. The amounts of the radioactive impurities (56)Co and (57)Co were assessed. A comparison of the three investigated production routes is given. PMID- 26686975 TI - Food safety concerns of fast food consumers in urban Ghana. AB - In Ghana, out-of-home ready-to-eat foods including fast food generally have been associated with food safety problems. Notwithstanding, fast food production and consumption are increasing in Ghana and therefore this study sought to determine the food safety issues of importance to consumers and the extent to which they worry about them. First, through three focus group discussions on consumers' personal opinions about food safety issues, some emergent themes were obtained, which were used to construct an open-ended questionnaire administered face-to face to 425 respondents systematically sampled from 20 fast food restaurants in Accra. Findings showed that most fast food consumers were concerned about food hazards such as pesticide residue in vegetables, excessive use of artificial flavour enhancers and colouring substances, bacterial contamination, migrated harmful substances from plastic packages, and general unhygienic conditions under which food is prepared and sold. Consumers also raised concerns about foodborne diseases such as cholera, typhoid, food poisoning, diarrhoea, bird flu and swine flu. The logistic regression model showed that being male increased the likelihood of worrying about general food safety issues and excessive use of flavour enhancers than in females while being youthful increased the likelihood of being worried about typhoid fever than in older consumers. These findings imply that consumers in urban Ghana are aware and concerned about current trends of food safety and foodborne disease challenges in the country. Therefore, efforts targeted at improving food safety and reducing incidences of foodborne diseases should not only focus on public awareness creation but should also design more comprehensive programmes to ensure the making of food safety rules and guidelines and enforcing compliance to facilitate availability and consumers' choice of safe foods. PMID- 26686976 TI - Relative motion between the flexor digitorum superficialis tendon and paratenon in zone V increases with wrist flexion angle. AB - Carpal tunnel syndrome is characterized by non-inflammatory fibrosis of the subsynovial connective tissue (SSCT), a paratenon-like structure inside the carpal tunnel. This pathology suggests repetitive and/or excessive shear forces are involved in injury development. We assessed relative motion between the flexor digitorum superficialis (FDS) tendon and adjacent paratenon in Zone V using colour Doppler imaging as 16 healthy participants completed three long finger movements (metacarpophalangeal joint flexion, proximal and distal interphalangeal joint flexion, full finger flexion) in three wrist postures (30 degrees extension, 0 degrees , 30 degrees flexion). While the type of finger movement did not affect tendon-paratenon relative motion, we found a significant main effect of wrist posture (p < 0.001). Relative displacement between the FDS tendon and paratenon (as a percentage of tendon displacement) increased from 27.2% (95%CI = 24.8-29.5%) in 30 degrees wrist extension to 39.9% (95%CI = 37.3 42.4%) in 30 degrees wrist flexion. Optical motion capture confirmed that wrist posture did not affect metacarpophalangeal joint range of motion (p = 0.265) or proximal interphalangeal joint range of motion (p = 0.582). These results indicate that relative motion increased due to paratenon strain when the wrist was flexed. While our findings agree with previous cadaveric research in wrist flexion, we found that relative displacement decreased in 30 degrees wrist extension (compared to 0 degrees ). These results differ from cadaveric research, possibly due to challenges maintaining anatomic fidelity of the viscoelastic paratenon tissue in vitro. Overall, our study suggests a greater susceptibility to shear injury during repetitive finger movements, particularly when the wrist is flexed. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1248-1255, 2016. PMID- 26686977 TI - Tailored and biodegradable poly(2-oxazoline) microbeads as 3D matrices for stem cell culture in regenerative therapies. AB - We present the synthesis of hydrogel microbeads based on telechelic poly(2 oxazoline) (POx) crosslinkers and the methacrylate monomers (HEMA, METAC, SPMA) by inverse emulsion polymerization. While in batch experiments only irregular and ill-defined beads were obtained, the preparation in a microfluidic (MF) device resulted in highly defined hydrogel microbeads. Variation of the MF parameters allowed to control the microbead diameter from 50 to 500 MUm. Microbead elasticity could be tuned from 2 to 20 kPa by the POx:monomer composition, the POx chain length, net charge of the hydrogel introduced via the monomer as well as by the organic content of the aqueous phase. The proliferations of human mesenchymal stem cells (hMSCs) on the microbeads were studied. While neutral, hydrophilic POx-PHEMA beads were bioinert, excessive colonization of hMSCs on charged POx-PMETAC and POx-PSPMA was observed. The number of proliferated cells scaled roughly linear with the METAC or SPMA comonomer content. Additional collagen I coating further improved the stem cell proliferation. Finally, a first POx-based system for the preparation of biodegradable hydrogel microcarriers is described and evaluated for stem cell culturing. PMID- 26686978 TI - An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans. AB - Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP 1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity. PMID- 26686979 TI - A pH-Driven and photoresponsive nanocarrier: Remotely-controlled by near-infrared light for stepwise antitumor treatment. AB - The hollow gold nanospheres (HAuNS) have shown medicinal promise due to their inert and nontoxic properties with unique photothermal therapy capabilities. In this study, the electrostatic approach was employed to successfully absorb Chlorin e6 (Ce6) simultaneously with the pH (low) insertion peptide (pHLIP) onto surface of HAuNS, forming HAuNS-pHLIP-Ce6 with desirable pH-driven and NIR light stimulated controlled therapeutical effect. The HAuNS-pHLIP-Ce6 experienced hyperthermia within 5 min of laser exposure, which marked the photothermal therapy (PTT) and deduced the agents release due to the reduction of electrostatic interaction. The improved strategy facilitated a stepwise photoresponsive system capable of active accumulation and retention effects, photothermal ablation of tumor cells, release of photosensitizers (PS), and subsequently photodynamic therapy (PDT) in a single light irradiation session. The smart delivery system had been proved with multi-functionalities via conjugated targeting ligand and PS. The external absorption of patient tailored medication combinations was also possible with this treatment platform. PMID- 26686980 TI - Characterization of a Strain of Fukuyoa paulensis (Dinophyceae) from the Western Mediterranean Sea. AB - A single cell of the dinoflagellate genus Fukuyoa was isolated from the island of Formentera (Balearic Islands, west Mediterranean Sea), cultured, and characterized by morphological and molecular methods and toxin analyses. This is the first report of the Gambierdiscus lineage (genera Fukuyoa and Gambierdiscus) from the western Mediterranean Sea, which is cooler than its eastern basin. Molecular analyses revealed that the Mediterranean strain belongs to F. paulensis and that it bears LSU rDNA sequences identical to New Zealand, Australian, and Brazilian strains. It also shared an identical sequence of the more variable ITS rDNA with the Brazilian strain. Toxin analyses showed the presence of maitotoxin, 54-deoxyCTX1B, and gambieric acid A. This is the first observation of the two latter compounds in a Fukuyoa strain. Therefore, both Gambierdiscus and Fukuyoa should be considered when as contributing to ciguatera fish poisoning. Different strains of Fukuyoa form a complex of morphologically cryptic lineages where F. paulensis stands as the most distantly related nominal species. The comparison of the ITS2 secondary structures revealed the absence of CBCs among strains. The study of the morphological and molecular traits depicted an unresolved taxonomic scenario impacted by the low strains sampling. PMID- 26686981 TI - Coronary artery ectasia in Noonan syndrome: Report of an individual with SOS1 mutation and literature review. AB - Noonan syndrome (NS) is the second most frequent hereditary syndrome with cardiac involvement. Pulmonary valve stenosis and hypertrophic cardiomyopathy are the most prevalent cardiovascular abnormalities. We report on a 14-year-old girl with NS due to SOS1 mutation with pulmonary stenosis and idiopathic coronary ectasia. To the best of our knowledge, this is the first report describing coronary ectasia in a patient with NS secondary to a SOS1 mutation. We include a literature review of this rare association. PMID- 26686982 TI - Perfluorooctanoic Acid Degradation Using UV-Persulfate Process: Modeling of the Degradation and Chlorate Formation. AB - In this study, we investigated the destruction and by-product formation of perfluorooctanoic acid (PFOA) using ultraviolet light and persulfate (UV-PS). Additionally, we developed a first-principles kinetic model to simulate both PFOA destruction and by-product and chlorate (ClO3(-)) formation in ultrapure water (UW), surface water (SW), and wastewater (WW). PFOA degradation was significantly suppressed in the presence of chloride and carbonate species and did not occur until all the chloride was converted to ClO3(-) in UW and for low DOC concentrations in SW. The model was able to simulate the PS decay, pH changes, radical concentrations, and ClO3(-) formation for UW and SW. However, our model was unable to simulate PFOA degradation well in WW, possibly from PS activation by NOM, which in turn produced sulfate radicals. PMID- 26686983 TI - Conversed mutagenesis of an inactive peptide to ASIC3 inhibitor for active sites determination. AB - Peptide Ugr9-1 from the venom of sea anemone Urticina grebelnyi selectively inhibits the ASIC3 channel and significantly reverses inflammatory and acid induced pain in vivo. A close homolog peptide Ugr 9-2 does not have these features. To find the pharmacophore residues and explore structure-activity relationships of Ugr 9-1, we performed site-directed mutagenesis of Ugr 9-2 and replaced several positions by the corresponding residues from Ugr 9-1. Mutant peptides Ugr 9-2 T9F and Ugr 9-2 Y12H were able to inhibit currents of the ASIC3 channels 2.2 times and 1.3 times weaker than Ugr 9-1, respectively. Detailed analysis of the spatial models of Ugr 9-1, Ugr 9-2 and both mutant peptides revealed the presence of the basic-aromatic clusters on opposite sides of the molecule, each of which is responsible for the activity. Additionally, Ugr9-1 mutant with truncated N- and C-termini retained similar with the Ugr9-1 action in vitro and was equally potent in vivo model of thermal hypersensitivity. All together, these results are important for studying the structure-activity relationships of ligand-receptor interaction and for the future development of peptide drugs from animal toxins. PMID- 26686984 TI - Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin. AB - Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3 indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected. PMID- 26686985 TI - Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform. AB - Here we describe a robust, microfluidic technique to generate and analyze 3D tumor spheroids, which resembles tumor microenvironment and can be used as a more effective preclinical drug testing and screening model. Monodisperse cell-laden alginate droplets were generated in polydimethylsiloxane (PDMS) microfluidic devices that combine T-junction droplet generation and external gelation for spheroid formation. The proposed approach has the capability to incorporate multiple cell types. For the purposes of our study, we generated spheroids with breast cancer cell lines (MCF-7 drug sensitive and resistant) and co-culture spheroids of MCF-7 together with a fibroblast cell line (HS-5). The device has the capability to house 1000 spheroids on chip for drug screening and other functional analysis. Cellular viability of spheroids in the array part of the device was maintained for two weeks by continuous perfusion of complete media into the device. The functional performance of our 3D tumor models and a dose dependent response of standard chemotherapeutic drug, doxorubicin (Dox) and standard drug combination Dox and paclitaxel (PCT) was analyzed on our chip-based platform. Altogether, our work provides a simple and novel, in vitro platform to generate, image and analyze uniform, 3D monodisperse alginate hydrogel tumors for various omic studies and therapeutic efficiency screening, an important translational step before in vivo studies. PMID- 26686986 TI - Paternal intergenerational epigenetic response to heat exposure in male Wild guinea pigs. AB - Epigenetic modifications, of which DNA methylation is the best studied one, can convey environmental information through generations via parental germ lines. Past studies have focused on the maternal transmission of epigenetic information to the offspring of isogenic mice and rats in response to external changes, whereas heterogeneous wild mammals as well as paternal epigenetic effects have been widely neglected. In most wild mammal species, males are the dispersing sex and have to cope with differing habitats and thermal changes. As temperature is a major environmental factor we investigated if genetically heterogeneous Wild guinea pig (Cavia aperea) males can adapt epigenetically to an increase in temperature and if that response will be transmitted to the next generation(s). Five adult male guinea pigs (F0) were exposed to an increased ambient temperature for 2 months, i.e. the duration of spermatogenesis. We studied the liver (as the main thermoregulatory organ) of F0 fathers and F1 sons, and testes of F1 sons for paternal transmission of epigenetic modifications across generation(s). Reduced representation bisulphite sequencing revealed shared differentially methylated regions in annotated areas between F0 livers before and after heat treatment, and their sons' livers and testes, which indicated a general response with ecological relevance. Thus, paternal exposure to a temporally limited increased ambient temperature led to an 'immediate' and 'heritable' epigenetic response that may even be transmitted to the F2 generation. In the context of globally rising temperatures epigenetic mechanisms may become increasingly relevant for the survival of species. PMID- 26686987 TI - Acute cholecystitis mimicking or accompanying cardiovascular disease among Japanese patients hospitalized in a Cardiology Department. AB - BACKGROUND: Acute cholecystitis sometimes displays symptoms and electrocardiographic changes mimicking cardiovascular problems. It may also coexist with cardiovascular disorders. We analyzed the clinical characteristic of the cardiac patients who were diagnosed with acute cholecystitis during hospitalization in the cardiology department. METHODS: Using the department database, we identified 16 patients who were diagnosed with acute cholecystitis during the hospitalization in the cardiology department between June 2010 and June 2014. RESULTS: Five patients who were initially suspected to have cardiac problems (acute coronary syndrome, four patients; Adams-Stokes syndrome, one patient) owing to their symptoms were subsequently diagnosed with acute cholecystitis. Two of these patients showed electrocardiographic changes mimicking myocardial ischemia, and three tested positive for a biomarker (heart type fatty acid binding protein) of acute myocardial injury. The 11 remaining cardiac patients were diagnosed with acute cholecystitis during their hospitalization or at the time of admission. Prolonged fasting and/or staying in an intensive care unit (ICU) may have contributed to their condition. Among these 11 patients, aortic dissection was the most prevalent underlying cardiac condition, affecting 5 patients. CONCLUSIONS: Although it is a rare condition, acute cholecystitis may coexist with or be misdiagnosed as a cardiovascular disorder. This possibility should not be overlooked in cardiac patients because a delay in treatment may result in critical complications. PMID- 26686990 TI - The roadmap of WT1 protein expression in the human fetal heart. AB - The transcription factor Wilms' Tumor-1 (WT1) is essential for cardiac development. Deletion of Wt1 in mice results in disturbed epicardial and myocardial formation and lack of cardiac vasculature, causing embryonic lethality. Little is known about the role of WT1 in the human fetal heart. Therefore, as a first step, we analyzed the expression pattern of WT1 protein during human cardiac development from week 4 till week 20. WT1 expression was apparent in epicardial, endothelial and endocardial cells in a spatiotemporal manner. The expression of WT1 follows a pattern starting at the epicardium and extending towards the lumen of the heart, with differences in timing and expression levels between the atria and ventricles. The expression of WT1 in cardiac arterial endothelial cells reduces in time, whereas WT1 expression in the endothelial cells of cardiac veins and capillaries remains present at all stages studied. This study provides for the first time a detailed description of the expression of WT1 protein during human cardiac development, which indicates an important role for WT1 also in human cardiogenesis. PMID- 26686988 TI - Thrombospondins in the transition from myocardial infarction to heart failure. AB - The heart's reaction to ischemic injury from a myocardial infarction involves complex cross-talk between the extra-cellular matrix (ECM) and different cell types within the myocardium. The ECM functions not only as a scaffold where myocytes beat synchronously, but an active signaling environment that regulates the important post-MI responses. The thrombospondins are matricellular proteins that modulate cell--ECM interactions, functioning as "sensors" that mediate outside-in and inside-out signaling. Thrombospondins are highly expressed during embryonic stages, and although their levels decrease during adult life, can be re expressed in high quantities in response to cardiac stress including myocardial infarction and heart failure. Like a Swiss-army knife, the thrombospondins possess many tools: numerous binding domains that allow them to interact with other elements of the ECM, cell surface receptors, and signaling molecules. It is through these that the thrombospondins function. In the present review, we provide basic as well as clinical evidence linking the thrombospondin proteins with the post myocardial infarction response, including inflammation, fibrotic matrix remodeling, angiogenesis, as well as myocyte hypertrophy, apoptosis, and contractile dysfunction in heart failure. We will describe what is known regarding the intracellular signaling pathways that are involved with these responses, paving the road for future studies identifying these proteins as therapeutic targets for cardiac disease. PMID- 26686989 TI - The TGF-beta pathway mediates doxorubicin effects on cardiac endothelial cells. AB - Elevated ALK4/5 ligands including TGF-beta and activins have been linked to cardiovascular remodeling and heart failure. Doxorubicin (Dox) is commonly used as a model of cardiomyopathy, a condition that often precedes cardiovascular remodeling and heart failure. In 7-8-week-old C57Bl/6 male mice treated with Dox we found decreased capillary density, increased levels of ALK4/5 ligand and Smad2/3 transcripts, and increased expression of Smad2/3 transcriptional targets. Human cardiac microvascular endothelial cells (HCMVEC) treated with Dox also showed increased levels of ALK4/5 ligands, Smad2/3 transcriptional targets, a decrease in proliferation and suppression of vascular network formation in a HCMVEC and human cardiac fibroblasts co-culture assay. Our hypothesis is that the deleterious effects of Dox on endothelial cells are mediated in part by the activation of the TGF-beta pathway. We used the inhibitor of ALK4/5 kinases SB431542 (SB) in concert with Dox to ascertain the role of TGF-beta pathway activation in doxorubicin induced endothelial cell defects. SB prevented the suppression of HCMVEC proliferation in the presence of TGF-beta2 and activin A, and alleviated the inhibition of HCMVEC proliferation by Dox. SB also prevented the suppression of vascular network formation in co-cultures of HCMVEC and human cardiac fibroblasts treated with Dox. Our results show that the inhibition of the TGF-beta pathway alleviates the detrimental effects of Dox on endothelial cells in vitro. PMID- 26686991 TI - The impact of educational workshops on individuals at risk for glaucoma in the Philadelphia Glaucoma Detection and Treatment Project. AB - OBJECTIVES: The purpose of this study was to investigate the impact of educational workshops, led by community health educators, on the level of knowledge, perceived risk of glaucoma, and rate of attendance in a subsequent glaucoma detection examination. METHODS: Participants attended an educational workshop about glaucoma and completed an 8-question pre- and post-test to assess knowledge. A paired samples t-test assessed mean differences in composite pre- and post-test scores, correct responses for each question, and perceived risk of glaucoma after the workshop. RESULTS: Seven hundred and seven (707) pre- and post test surveys were completed. There was a significant increase in the level of knowledge about glaucoma as reflected in the pre- and post-test composite scores (M=3.86, SD=1.95 vs. M=4.97, SD=1.82, P<0.001). In the 5 largest community sites, 44% (n=221/480) of the participants who attended an educational workshop scheduled a glaucoma detection examination appointment and 76% (n=160/211) of these participants completed this eye examination in the community setting. CONCLUSIONS: Educational workshops increased knowledge and awareness about glaucoma and were helpful in recruiting patients for community-based glaucoma detection examinations. PRACTICE IMPLICATIONS: We recommend including educational workshops when conducting community-based outreach programs. PMID- 26686966 TI - The Association of Statin Use with Cataract Progression and Cataract Surgery: The AREDS2 Report Number 8. PMID- 26686992 TI - Responding empathically to patients: Development, implementation, and evaluation of a communication skills training module for oncology nurses. AB - OBJECTIVE: The purpose of this paper is to report on the development, implementation, and evaluation of a Communication Skills Training (CST) module for inpatient oncology nurses on how to respond empathically to patients. METHODS: 248 nurses from a USA cancer center participated in a CST module on responding empathically to patients. Nurses completed pre- and post-training Standardized Patient Assessments (SPAs), a survey on their confidence in and intent to utilize skills taught, and a six-month post-training survey of self reported use of skills. RESULTS: Results indicate that nurses were satisfied with the module, reporting that agreement or strong agreement to 5 out of 6 items assessing satisfaction 96.7%-98.0% of the time. Nurses' self-efficacy in responding empathically significantly increased pre- to post-training. Additionally, nurses showed empathy skill improvement in the post-SPAs. Finally, 88.2% of nurses reported feeling confident in using the skills they learned post training and reported an increase of 42-63% in the use of specific empathic skills. CONCLUSIONS: A CST module for nurses in responding empathically to patients showed feasibility, acceptability, and improvement in self-efficacy as well as skill uptake. PRACTICE IMPLICATIONS: This CST module provides an easily targeted intervention for improving nurse-patient communication and patient centered care. PMID- 26686993 TI - Long-Term Survival Benefit of Coronary Revascularization in Patients Undergoing Stress Myocardial Perfusion Imaging. AB - BACKGROUND: We assessed the relationship between clinical outcome and coronary revascularization according to stress-gated myocardial perfusion single-photon emission computed tomography (MPS) in an observational series of patients with suspected or known coronary artery disease (CAD), on long-term follow-up. METHODS AND RESULTS: The study group consisted of 2,059 patients. During a median follow up of 61 months, 184 events occurred (126 cardiac deaths and 58 non-fatal MI). The impact of revascularization during follow-up on event-free survival was evaluated using an extended Cox regression model, adjusting for potential clinical and MPS confounders. Revascularization was treated as a binary non reversible time-dependent covariate. Predefined interactions tested were: (1) revascularization and summed difference score (SDS); (2) revascularization and post-stress left ventricular (LV) ejection fraction (EF); and (3) SDS and post stress LVEF. Revascularization had a significant effect on event-free survival (adjusted HR, 0.19; P<0.001). Significant interactions were found between revascularization and SDS (P=0.045), and between LVEF and SDS (P=0.015). The protective effect of revascularization increased as SDS increased. For SDS <6 the reduction in HR was detectable only for reduced LVEF. CONCLUSIONS: Both the degree of stress-induced ischemia and LVEF predict the effect of revascularization on outcome in patients with suspected or known CAD. The protective effect of revascularization appears to be greater in patients with severe ischemia and preserved LVEF. PMID- 26686994 TI - The Who, What, Why, When, How and Where of Vasospastic Angina. AB - Ischemic heart disease involves both "structural" and/or "functional" disorders of the coronary circulation. Structural atherosclerotic coronary artery disease (CAD) is well recognized, with established diagnostic and treatment strategies. In contrast, "functional CAD" has received limited attention and is seldom actively pursued in the investigation of ischemic heart disease. Vasospastic angina encompasses "functional CAD" attributable to coronary artery spasm and this "state of the art" consensus statement reviews contemporary aspects of this disorder. Patients with vasospastic angina typically present with angina at rest that promptly responds to short-acting nitrates and is associated with transient ischemic ECG changes. Although spontaneous episodes may be documented, provocative spasm testing may be required to confirm the diagnosis. It is important to diagnose vasospastic angina because it may be associated with major adverse events that can be prevented with the use of appropriate vasodilator therapy (eg, calcium-channel blockers) and the avoidance of aggravating stimuli (eg, smoking). Future studies are required to clarify the underlying pathophysiology, natural history and effective treatments for patients refractory to conventional therapy. PMID- 26686995 TI - In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate. AB - Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific. PMID- 26686996 TI - Safety evaluation of nuclease P1 from Penicillium citrinum. AB - Nuclease P1 has been widely used in the food industry to enhance or create flavor. One commercial source of this enzyme is Penicillium citrinum, an anamorphic mesophilic fungus with a long history of safe use in Europe and Asia as a fermentation organism used in the production of ribonucleases. Given the intended use in food for human consumption, and noting its potential presence at trace levels in finished products, a series of safety studies including an in vitro Ames and chromosome aberration assay, an in vivo rat erythrocyte micronucleus assay and a 90-day oral toxicity study in rats were conducted. No mutagenic activity was observed in the Ames assay. Equivocal activity in the chromosome aberration assay was not replicated in the micronucleus assay at doses of up to 1007 mg total organic solids (TOS)/kg body weight (bw)/day. Following oral administration of nuclease P1 at dosages of 10.1, 101 or 1007 mg TOS/kg bw/day to Sprague-Dawley rats, no adverse effects on any study parameter were observed. The no-observed-adverse-effect level was considered to be 1007 mg TOS/kg bw/day. The results of the genotoxicity studies and subchronic rat study support the safe use in food production of nuclease P1 produced from P. citrinum. PMID- 26686998 TI - High predicted strain coverage by the multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland. AB - Neisseria meningitidis of serogroup B (MenB) is currently responsible for more than 70% of cases of invasive meningococcal disease (IMD) in Poland and Europe as a whole. The aim of this study was to estimate strain coverage of a multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland; the meningococcal antigen typing system (MATS) was used to test a panel of 196 invasive MenB strains isolated in Poland in 2010 and 2011. The strains were also characterized by MLST and sequencing of porA, factor H-binding protein (fHbp), Neisserial heparin-binding antigen (nhba) and Neisserial adhesin A (nadA) genes. MATS and molecular data were analyzed independently and in combination. The MATS results predicted that 83.7% (95% CI: 78.6-91.0%) of isolates would be covered by the 4CMenB vaccine; 59.2% by one vaccine antigen, 19.9% by two and 4.6% by three antigens. Coverage by each antigen was as follows: fHbp 73.0% (95% CI: 68.9 77.5%), NHBA 28.6% (95% CI: 13.3-47.4%), NadA 1.0% (95% CI: 1.0-2.0%) and PorA 10.2%. Molecular analysis revealed that the most frequent clonal complexes (ccs) were cc32 (33.2%), cc18 (17.9%) and cc41/44 (15.8%) with estimated coverage of 98.5%, 88.6% and 93.5%, respectively. Consistent with findings for other European countries, our study predicts high coverage by the 4CMenB vaccine in Poland. PMID- 26686997 TI - Trends in silicosis prevalence and the healthy worker effect among gold miners in South Africa: a prevalence study with follow up of employment status. AB - BACKGROUND: Given the intimate association between silicosis and tuberculosis, understanding the epidemiology of the South African gold mining industry silicosis epidemic is essential to current initiatives to control both silicosis and tuberculosis in this population, one of the most heavily affected globally. The study's objectives were to compare the prevalence of silicosis among working black gold miners in South Africa during 2004-2009 to that of previous studies, including autopsy series, and to analyse the influence of silicosis and/or tuberculosis on exiting employment. METHODS: Routine chest radiographs from a cohort of gold miners were read for silicosis by an experienced reader (I), and a subset re-read by a B-trained reader (II). Two methods of presenting the readings were used. Additionally, with baseline status of silicosis and previous or active tuberculosis as predictors, survival analysis examined the probability of exiting the workforce for any reason during 2006-2011. RESULTS: Reader I read 11 557 chest radiographs and reader II re-read 841. Overall, silicosis prevalence (ILO >= 1/0: 5.7 and 6.2% depending on reader method) was similar to the age adjusted prevalence found in a large study in 1984 (5.0%). When comparison was restricted to a single mine shaft previously studied in 2000, a decline in prevalence (ILO >= 1/1) was suggested for one of the reading methods (duration adjusted 20.5% vs. 13.0% in the current study). These findings are discordant with a long-term rising autopsy prevalence of silicosis over this period. Overall, relative to miners with neither disease, the adjusted hazard ratio for exiting employment during the follow-up period was 1.54 for baseline silicosis [95% confidence interval (CI) 1.17, 2.04], 1.71 for tuberculosis (95% CI 1.51, 1.94) and 1.53 for combined disease (95% CI 1.20, 1.96). CONCLUSIONS: This study found, a) there was no significant decline in overall silicosis prevalence among working black miners in the South African gold mining industry between 1984 and 2004-2009, and b) a possible decline at one mine shaft more recently. In the absence of evidence of declining respirable silica concentrations between the 1980s and 2000s, the trends found are plausibly due to a healthy worker survivor effect, which may be accelerating. PMID- 26686999 TI - Development of a more efficient hepatitis B virus vaccine by targeting hepatitis B virus preS to dendritic cells. AB - BACKGROUND: Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccinees. Therefore, there remains an urgent need to develop a safe and effective HBV vaccine. METHODS: In this study, we developed an effective and economical method for producing the HBV vaccine by using the high binding capacity of biotin streptavidin. The preS antigen of HBV was fused with the core streptavidin (cSA) moiety (preS-cSA) and highly expressed in Escherichia coli. We investigated whether the preS-cSA protein could target dendritic cells (DCs) by binding a biotinylated antibody against the DC receptor CD205 (biotin-alphaCD205). Moreover, we evaluated the preS-cSA/biotin-alphaCD205 complex as a candidate vaccine by detecting the humoral and cellular immune responses elicited by this vaccine. RESULTS: Our data show that the preS-cSA/biotin-alphaCD205 complex targeted DCs and induced high anti-HBV antibody titers of IgG2a, IgG1, and IgG in vivo. Furthermore, vaccination with the preS-cSA/biotin-alphaCD205 complex prevented HBV infection in female mice. More interestingly, this novel vaccine exerted a therapeutic role in mice with HBV infection. CONCLUSIONS: Taken together, our results reveal that the preS-cSA/biotin-alphaCD205 vaccine induces effective immunological protection against HBV, and is a promising candidate for preventing HBV infections. PMID- 26687000 TI - Antioxidant and antimicrobial proprieties of chitin and chitosan extracted from Parapenaeus Longirostris shrimp shell waste. AB - INTRODUCTION: Chitosan, the linear polymer, is produced by alkali deacetylation of chitin (CHI). Recently chitin and chitosan were attracted marked interest due to their biocompatibility, biodegradability and non-toxicity. MATERIALS AND METHODS: In this study, chitin was extracted from shrimp shell (Parapenaeus longirostris) and chitosan was deacetylated by classical and ultrasound-assisted method. The identification of functional groups and the determination of degree of deacetylation of chitin (CHI), classical deacetylated chitosan (CDC) and ultrasound-assisted deacetylated chitosan (UDC) were carried through Fourier Transform-Infrared Spectroscopy. Their antimicrobial and antioxidant activity were also investigated. RESULTS: The degree of deacetylation of CHI, CDC and UDC is 33.64%, 73.68% and 83.55%, respectively. Results showed that CHI, CDC and UDC exhibited a good antimicrobial activity against (S. aureus, E. coli, P. aeruginosa, K. pneumonia) and (C. albicans and C. parapsilosis). The scavenging ability of CHI, CDC and UDC on 1,1-diphenyl-2-picrylhydrazyl radicals is ranging from 4.71% to 21.25%, 11.45% to 32.78% and 18.27% to 44.17%, respectively, at the concentrations of 0.25 to 1mg/mL. The inhibition of lipid peroxidation with thiobarbituric acid-reacting substances is ranging from 11.7% to 51.63%, 17.24% to 63.52% and 29.31% to 77.39%, respectively, at varying concentrations of 0.25 to 1mg/mL. CONCLUSION: The effectiveness of CHI, CDC and UDC is correlated with their degree of deacetylation. The results indicate the possibility of exploiting chitin and chitosan as antimicrobial agent. PMID- 26687001 TI - Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. AB - BACKGROUND: We systematically reviewed and performed a meta-analysis of the available data regarding neoadjuvant chemo- and/or radiotherapy with special emphasis on tumor response/progression rates, toxicities, and clinical benefit, i.e. resection probabilities and survival estimates. METHODS AND FINDINGS: Trials were identified by searching PUBMED, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1966 to Feb 2015. A total of 18 studies (n = 959) were analyzed. the estimated fraction of patients with complete response was 2.8% (CI 0.8-4.7%) and with partial response 28.7% (CI 18.9%-38.5%). Stable disease was averaged to 45.9% (CI 32.9%-58.9%) in all patients and tumor progression under therapy occurred by estimation in 16.9% (CI 10.2%-23.6%) of the patients. The weighted frequency of those who underwent resection was 65.3% (CI 54.2%-76.5%), and the proportion of R0 resection amounted to 57.4% (CI 48.2%-66.5%). The weighted mean of median survival amounted to 17.9 months (range: 14.7-21.2 months) for the overall cohort of patients, 25.9 months (range: 21.1-30.7 months) for those who were resected, and 11.9 months (range: 10.4-13.5 months) for unresected patients. CONCLUSIONS: The resection and R0 resection rates in the group of borderline resectable tumor patients after neoadjuvant therapy are similar to the resectable tumor patients, much higher than those in unresectable tumor patients. The survival estimates of borderline resectable tumor patients after neoadjuvant therapy were similar to resectable tumor patients. Patients with borderline resectable pancreatic cancer should be included in neoadjuvant protocols and subsequently be reevaluated for resection. How to find chemo responsiveness before neoadjuvant chemotherapy so as to give individualized treatment is still an important issue. PMID- 26687003 TI - Erratum to: A new anatomic trait for identifying the mendosal suture in young children: the mendosal-lambdoidal angle. PMID- 26687002 TI - A Dual Role of Graphene Oxide Sheet Deposition on Titanate Nanowire Scaffolds for Osteo-implantation: Mechanical Hardener and Surface Activity Regulator. AB - Scaffold biomaterials with open pores and channels are favourable for cell growth and tissue regeneration, however the inherent poor mechanical strength and low surface activity limit their applications as load-bearing bone grafts with satisfactory osseointegration. In this study, macro-porous graphene oxide (GO) modified titanate nanowire scaffolds with desirable surface chemistry and tunable mechanical properties were prepared through a simple hydrothermal process followed by electrochemical deposition of GO nanosheets. The interconnected and porous structure of the GO/titanate nanowire scaffolds provides a large surface area for cellular attachment and migration and displays a high compressive strength of approximately 81.1 MPa and a tunable Young's modulus over the range of 12.4-41.0 GPa, which satisfies site-specific requirements for implantation. Surface chemistry of the scaffolds was modulated by the introduction of GO, which endows the scaffolds flexibility in attaching and patterning bioactive groups (such as -OH, -COOH and -NH2). In vitro cell culture tests suggest that the GO/titanate nanowire scaffolds act as a promising biomaterial candidate, in particular the one terminated with -OH groups, which demonstrates improved cell viability, and proliferation, differentiation and osteogenic activities. PMID- 26687004 TI - Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells. AB - Dynamic post-translational modification of RNA polymerase II (RNAPII) coordinates the co-transcriptional recruitment of enzymatic complexes that regulate chromatin states and processing of nascent RNA. Extensive phosphorylation of serine residues at the largest RNAPII subunit occurs at its structurally-disordered C terminal domain (CTD), which is composed of multiple heptapeptide repeats with consensus sequence Y1-S2-P3-T4-S5-P6-S7. Serine-5 and Serine-7 phosphorylation mark transcription initiation, whereas Serine-2 phosphorylation coincides with productive elongation. In vertebrates, the CTD has eight non-canonical substitutions of Serine-7 into Lysine-7, which can be acetylated (K7ac). Here, we describe mono- and di-methylation of CTD Lysine-7 residues (K7me1 and K7me2). K7me1 and K7me2 are observed during the earliest transcription stages and precede or accompany Serine-5 and Serine-7 phosphorylation. In contrast, K7ac is associated with RNAPII elongation, Serine-2 phosphorylation and mRNA expression. We identify an unexpected balance between RNAPII K7 methylation and acetylation at gene promoters, which fine-tunes gene expression levels. PMID- 26687005 TI - Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins. AB - Using a new bioinformatic method to analyze ribosome profiling data, we show that 40% of lncRNAs and pseudogene RNAs expressed in human cells are translated. In addition, ~35% of mRNA coding genes are translated upstream of the primary protein-coding region (uORFs) and 4% are translated downstream (dORFs). Translated lncRNAs preferentially localize in the cytoplasm, whereas untranslated lncRNAs preferentially localize in the nucleus. The translation efficiency of cytoplasmic lncRNAs is nearly comparable to that of mRNAs, suggesting that cytoplasmic lncRNAs are engaged by the ribosome and translated. While most peptides generated from lncRNAs may be highly unstable byproducts without function, ~9% of the peptides are conserved in ORFs in mouse transcripts, as are 74% of pseudogene peptides, 24% of uORF peptides and 32% of dORF peptides. Analyses of synonymous and nonsynonymous substitution rates of these conserved peptides show that some are under stabilizing selection, suggesting potential functional importance. PMID- 26687006 TI - Dbx1 precursor cells are a source of inspiratory XII premotoneurons. AB - All behaviors require coordinated activation of motoneurons from central command and premotor networks. The genetic identities of premotoneurons providing behaviorally relevant excitation to any pool of respiratory motoneurons remain unknown. Recently, we established in vitro that Dbx1-derived pre-Botzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (Wang et al., 2014). Here, we further show that a subpopulation of Dbx1-derived intermediate reticular (IRt) neurons are rhythmically active during inspiration and project to the hypoglossal (XII) nucleus that contains motoneurons important for maintaining airway patency. Laser ablation of Dbx1 IRt neurons, 57% of which are glutamatergic, decreased ipsilateral inspiratory motor output without affecting frequency. We conclude that a subset of Dbx1 IRt neurons is a source of premotor excitatory drive, contributing to the inspiratory behavior of XII motoneurons, as well as a key component of the airway control network whose dysfunction contributes to sleep apnea. PMID- 26687007 TI - Targeting senescent cells enhances adipogenesis and metabolic function in old age. AB - Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18 month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22 month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism. PMID- 26687008 TI - Neural evidence accumulation persists after choice to inform metacognitive judgments. AB - The ability to revise one's certainty or confidence in a preceding choice is a critical feature of adaptive decision-making but the neural mechanisms underpinning this metacognitive process have yet to be characterized. In the present study, we demonstrate that the same build-to-threshold decision variable signal that triggers an initial choice continues to evolve after commitment, and determines the timing and accuracy of self-initiated error detection reports by selectively representing accumulated evidence that the preceding choice was incorrect. We also show that a peri-choice signal generated in medial frontal cortex provides a source of input to this post-decision accumulation process, indicating that metacognitive judgments are not solely based on the accumulation of feedforward sensory evidence. These findings impart novel insights into the generative mechanisms of metacognition. PMID- 26687010 TI - PDH45 transgenic rice maintain cell viability through lower accumulation of Na(+), ROS and calcium homeostasis in roots under salinity stress. AB - Salinity severely affects the growth/productivity of rice, which is utilized as major staple food crop worldwide. PDH45 (pea DNA helicase 45), a member of the DEAD-box helicase family, actively provides salinity stress tolerance, but the mechanism behind this is not well known. Therefore, in order to understand the mechanism of stress tolerance, sodium ion (Na(+)), reactive oxygen species (ROS), cytosolic calcium [Ca(2+)]cyt and cell viability were analyzed in roots of PDH45 transgenic-IR64 rice lines along with wild-type (WT) IR64 rice under salinity stress (100mM and 200 mM NaCl). In addition, the roots of salinity-tolerant (FL478) and susceptible (Pusa-44) rice varieties were also analyzed under salinity stress for comparative analysis. The results reveal that, under salinity stress (100mM and 200 mM NaCl), roots of PDH45 transgenic lines accumulate lower levels of Na(+), ROS and maintain [Ca(2+)]cyt and exhibit higher cell viability as compared with roots of WT (IR64) plants. Similar results were also obtained in the salinity-tolerant FL478 rice. However, the roots of WT and salinity susceptible Pusa-44 rice accumulated higher levels of Na(+), ROS and [Ca(2+)]cyt imbalance and lower cell viability during salinity stress, which is in contrast to the overexpressing PDH45 transgenic lines and salinity-tolerant FL478 rice. Further, to understand the mechanism of PDH45 at molecular level, comparative expression profiling of 12 cation transporters/genes was also conducted in roots of WT (IR64) and overexpressing PDH45 transgenic lines (L1 and L2) under salt stress (24h of 200 mM NaCl). The expression analysis results show altered and differential gene expression of cation transporters/genes in salt-stressed roots of WT (IR64) and overexpressing transgenic lines (L1 and L2). These observations collectively suggest that, under salinity stress conditions, PDH45 is involved in the regulation of Na(+) level, ROS production, [Ca(2+)]cyt homeostasis, cell viability and cation transporters in roots of PDH45 transgenic-IR64 rice and consequently provide salinity tolerance. Elucidating the detailed regulatory mechanism of PDH45 will provide a better understanding of salinity stress tolerance and further open new ways to manipulate genome to achieve higher agricultural production under stress. PMID- 26687011 TI - Neuroinformatics for Degenerate Brains. PMID- 26687009 TI - Structural basis of interprotein electron transfer in bacterial sulfite oxidation. AB - Interprotein electron transfer underpins the essential processes of life and relies on the formation of specific, yet transient protein-protein interactions. In biological systems, the detoxification of sulfite is catalyzed by the sulfite oxidizing enzymes (SOEs), which interact with an electron acceptor for catalytic turnover. Here, we report the structural and functional analyses of the SOE SorT from Sinorhizobium meliloti and its cognate electron acceptor SorU. Kinetic and thermodynamic analyses of the SorT/SorU interaction show the complex is dynamic in solution, and that the proteins interact with Kd = 13.5 +/- 0.8 MUM. The crystal structures of the oxidized SorT and SorU, both in isolation and in complex, reveal the interface to be remarkably electrostatic, with an unusually large number of direct hydrogen bonding interactions. The assembly of the complex is accompanied by an adjustment in the structure of SorU, and conformational sampling provides a mechanism for dissociation of the SorT/SorU assembly. PMID- 26687012 TI - Low temperature superplasticity and thermal stability of a nanostructured low carbon microalloyed steel. AB - We describe here for the first time the low temperature superplasticity of nanostructured low carbon steel (microalloyed with V, N, Mn, Al, Si, and Ni). Low carbon nanograined/ultrafine-grained (NG/UFG) bulk steel was processed using a combination of cold-rolling and annealing of martensite. The complex microstructure of NG/UFG ferrite and 50-80 nm cementite exhibited high thermal stability at 500 degrees C with low temperature elongation exceeding 100% (at less than 0.5 of the absolute melting point) as compared to the conventional fine grained (FG) counterpart. The low temperature superplasticity is adequate to form complex components. Moreover, the low strength during hot processing is favorable for decreasing the spring back and minimize die loss. PMID- 26687013 TI - Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment. AB - Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID- 26687014 TI - Thermal phase behavior and ion hopping in a 1,2,4-triazolium perfluorobutanesulfonate protic organic ionic plastic crystal. AB - Critical aspects of thermal behavior and the electrolytic properties of solid state Protic Organic Ionic Plastic Crystals (POIPCs) are unknown. We present molecular dynamics (MD) simulations on a perfect crystal and a vacancy model to probe such physical phenomena in POIPCs using 1,2,4-triazolium perfluorobutanesulfonate ([TAZ][pfBu]) as an example. The results show the existence of a rotator phase wherein the cations, although translationally ordered are disordered rotationally and exhibit a tumbling motion which significantly affects hydrogen bond lifetimes. van Hove correlation functions characterize the concerted hopping of ions (cation or anion) at 500 K. These results are substantiated by calculated free energy barriers (cation = 2.5 kcal mol(-1) and anion = 6 kcal mol(-1)) and suggest that proton and ion transport influenced by facile hydrogen bond dynamics in the rotator phase contribute to the solid-state conductivity of POIPCs. PMID- 26687015 TI - Response to "Total Vaginal Natural Orifice Transluminal Endoscopic Surgery Hysterectomy". PMID- 26687016 TI - Heterotopic Pregnancy After In Vitro Fertilization and Embryo Transfer After Bilateral Total Salpingectomy/Tubal Ligation: Case Report and Literature Review. AB - Heterotopic pregnancy is defined as the simultaneous occurrence of intrauterine and ectopic pregnancy, either of which may be single or multiple. It occurs in up to 1% of pregnancies after in vitro fertilization and embryo transfer. This article reports 2 rare cases of heterotopic pregnancy after in vitro fertilization and presents a literature review. In the first case, a 28-year-old woman had previous laparoscopic bilateral total salpingectomy for a right tubal pregnancy and a left hydrosalpinx. However, she had ovarian heterotopic pregnancy after a third in vitro fertilization cycle. Emergency laparotomy was performed. The synchronous intrauterine pregnancy continued with no further complications and ended in the delivery of a singleton term pregnancy. The second case combined interstitial and intrauterine pregnancies after bilateral tubal ligation for hydrosalpinges followed by in vitro fertilization and frozen embryo transfer. The possibility of heterotopic pregnancy after bilateral total salpingectomy/tubal ligation, although extremely rare, should also be considered by gynecologists when they treat an in vitro fertilization patient even though an intrauterine pregnancy has been confirmed. PMID- 26687017 TI - Observer variability in RECIST-based tumour burden measurements: a meta-analysis. AB - BACKGROUND: Response Evaluation Criteria in Solid Tumours (RECIST)-based tumour burden measurements involve observer variability, the extent of which ought to be determined. METHODS: A literature search identified studies on observer variability during manual measurements of tumour burdens via computed tomography according to the RECIST guideline. The 95% limit of agreement (LOA) values of relative measurement difference (RMD) were pooled using a random-effects model. RESULTS: Twelve studies were included. Pooled 95% LOAs of RMD in measuring unidimensional longest diameters of single lesions ranged from -22.1% (95% confidence interval [CI], -30.3% to -14.0%) to 25.4% (95% CI, 17.2% to 33.5%) between observers and -17.8% (95% CI, -23.6% to -11.9%) to 16.1% (95% CI, 10.1% to 21.8%) for a single observer. Pooled 95% LOAs of RMD in measuring the sum of multiple lesions ranged from -19.2% (95% CI, -23.7% to -14.9%) to 19.5% (95% CI, 15.2% to 23.9%) between observers, and -9.8% (95% CI, -19.0% to -0.3%) to 13.1% (95% CI, 3.6% to 22.6%) for a single observer. Pooled 95% LOA of RMD in calculating the interval change of tumour burden with a single lesion ranged from -31.3% (95% CI, -46.0% to -16.5%) to 30.3% (95% CI, 15.3% to 44.8%) between observers. Studies on calculating the interval change of tumour burden for a single observer or with multiple lesions were lacking. CONCLUSION: Interobserver RMD in measuring single tumour burden and calculating its interval change may exceed the 20% cut-off for progression. Variability decreased when tumour burden was measured by a single observer or assessed by the sum of multiple lesions. PMID- 26687018 TI - 'To preserve unity while almost allowing for chaos': Testing the aesthetic principle of unity-in-variety in product design. AB - Unity-in-variety is considered to be one of the oldest-known universal principles of beauty. However, little empirical research exists on how unity and variety together influence aesthetic appreciation. In three studies we investigated how unity and variety predict the aesthetic appreciation of a range of product designs, and further assessed whether perceived visual complexity and individual differences in regulatory focus influence this relationship. Our findings reveal that both unity and variety, while suppressing each other's effect, positively affect aesthetic appreciation. Hence, product designs that exhibit an optimum balance between unity and variety are aesthetically preferred. Furthermore, the research reveals that unity is the dominant factor in this relationship and facilitates the appreciation of variety. We discuss several theoretical and practical implications resulting from these studies. PMID- 26687019 TI - Additional information is not ignored: New evidence for information integration and inhibition in take-the-best decisions. AB - Ignoring information when making a decision is at the heart of the take-the-best (TTB) strategy, according to which decision makers only consider information about the most valid cue (TTB-relevant) and ignore less valid cues (TTB irrelevant). Results of four experiments, however, show that participants do not ignore information when cues are easily available (Experiments 1a, 1b, and 3) or when task instructions emphasize decision accuracy (Experiment 2). In all four experiments we found that the consistency between the TTB-relevant cue and a supposedly TTB-irrelevant cue systematically affected decision times and confidence ratings of even those participants whose choices were consistently driven by only the TTB-relevant cue. In Experiments 1a and 1b, we also found that these participants were more likely to ignore information when cues had to be acquired sequentially, suggesting that whether or not participants ignore information depends on information availability. Experiment 2 further showed that different task instructions (emphasizing decision accuracy vs. speed) affect whether or not participants ignore information. Finally, Experiment 3 addressed the question of how participants process information that, according to TTB, is considered irrelevant for their choices. We find first evidence that participants who consistently make choices in line with TTB inhibit information about a TTB irrelevant cue when this information conflicts with their decisions. Findings are considered and discussed in relation to current models of decision making. PMID- 26687021 TI - The challenge of metaproteomic analysis in human samples. PMID- 26687020 TI - Evaluation of the treatment of chronic chemotherapy-induced peripheral neuropathy using long-wave diathermy and interferential currents: a randomized controlled trial. AB - PURPOSE: The purpose was to investigate the effects of long-wave diathermy in combination with interferential currents (interferential therapy and long-wave diathermy at high power (ITH)) in comparison with long-wave diathermy at a power below the active treatment dose (long-wave diathermy at low power (LDL), control group) on sensory and motor symptoms in patients with chronic chemotherapy induced peripheral neuropathy (CIPN) in the lower extremities. METHODS: Sixty seven patients with chronic CIPN were randomized to 12 weeks of either ITH or LDL. Follow-up assessments were performed after the treatment period and at 37 weeks after randomization. The primary outcome was pain (Numeric Rating Scale (NRS)), and the secondary outcomes were discomfort, nerve symptoms, subjective measurement of dizziness (Dizziness Handicap Inventory), and balance. Differences within and between groups were analyzed. RESULTS: Pain intensity decreased significantly only in the LDL group directly after the treatment period from NRS median 25 to median 12.5 (P = 0.017). At the 37-week follow-up, no changes were detected, irrespective of group (NRS 13 vs. 20, P = 0.885). Discomfort decreased significantly in both groups at both 12 and 37 weeks after the baseline (P < 0.05). Balance disability showed significant declines in both groups at 12 and 37 weeks (P = 0.001/0.025 in the ITH group vs P = 0.001/<0.001 in the LDL group). Balance ability (tightened Romberg test) increased significantly at both 12 and 37 weeks in both groups (P = 0.004/<0.040 in the ITH group) but did not improve in the LDL group at any of the follow-up time points (P = 0.203 vs P = 0.383). The one-legged stance test was unchanged in the ITH group after 12 weeks but improved 37 weeks after baseline (P = 0.03). No significant changes were observed in the LDL group at any of the follow-up time points. CONCLUSION: This study provides no support for the use of a combination of long-wave diathermy and ITH as a treatment option for patients with chronic CIPN. However, the chronic CIPN symptoms decreased with time irrespective of the treatment. PMID- 26687022 TI - Interaction of metallacrown complexes with G-quadruplex DNA. AB - Interactions of the G-quadruplex (GQ) DNA with two pentacoordinate lanthanide (III) metallacrown (MC) complexes containing phenylalanine hydroxamic acid (pheHA) and copper(II) ions of the formula Eu 15-[MCCu,pheHA]-5 (1) and Tb 15 [MCCu,pheHA]-5 (2) were investigated. Binding of both metallacrowns to human telomeric G-quadruplex DNA was followed using CD spectroscopy, DNA melting profiles, and fluorescent intercalator displacement (FID) assay. A new G quadruplex binding assay based of quenching of Tb(III)-GQ luminescence was proposed and evaluated. All performed tests confirmed interactions of MCs with studied GQ structure. Binding affinities of MCs were appreciable (KMC ~2 5*10(5)M(-1)). Higher concentration of MCs (the ratio of GQ:MC above 2.5) caused destabilization of tetraplex structure of GQ as evidenced by CD spectroscopy, melting temperatures, and Tb(III)-GQ luminescence quenching results. PMID- 26687023 TI - Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains. AB - Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {[Ag(X-O)(phtz-N)]2(MU-phtz-N,N')2} were formed, X=NO3(-) (1), CF3SO3(-) (2) and ClO4(-) (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {[Ag(CF3SO3-O)(qz-N)]2}n (4) and {[Ag(qz-N)][BF4]}n (5). Complexes 1-5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0MUM against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC=2.9-29MUM) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1-5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. The binding of complexes 1 5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3. PMID- 26687024 TI - Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies. AB - We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy. PMID- 26687025 TI - Handgrip explosive force is correlated with mobility in the elderly women. AB - The analysis of explosive force, through rate of force development (RFD) and contractile impulse (CI), from handgrip strength data seems to be useful and promising information to study the aging of musculoskeletal system and health status. We aimed to test the hypothesis that, in elderly women, the handgrip explosive force could be better associated to the functional mobility than maximum handgrip strength. Handgrip strength and the performance of Timed Up & Go Test (TUG) were measured from sixty-five community-dwelling healthy elderly women. The average slope of the moment-time curve (Delta moment/Delta time) over the time interval of 0-200 ms relative to the onset of contraction was calculated to provide the RFD and CI. The highest strength achieved during the isometric contraction was used as maximum handgrip strength. Pearson correlations were used to assess the strength of the relationship between the handgrip strength parameters (Maximum strength and explosive force from 0-200 ms) and TUG test performance from older women. The correlation analysis showed that the TUG test performance was inversely correlated to the handgrip strength parameters, with better relationship with explosive force parameters. The handgrip explosive force seems to be a promising predictor of functional mobility of elderly women, since it showed a better relationship with functional mobility than maximum handgrip strength. PMID- 26687027 TI - Standardization of allergen products: 2. Detailed characterization of GMP produced recombinant Phl p 5.0109 as European Pharmacopoeia reference standard. AB - BACKGROUND: The Biological Standardization Programme of the European Directorate for Quality of Medicines and Healthcare (EDQM) aims at the establishment of well characterized reference standards based on recombinant allergens and validated assays for the quantification of major allergen content. The objective of this study was to examine the detailed physicochemical and immunological characterization of recombinant Phl p 5.0109, the second available allergen reference standard. METHODS: Recombinant Phl p 5.0109 PP5ar06007 was produced under GMP conditions and analyzed by an array of physicochemical and immunological methods for identity, quantity, homogeneity, and folding stability in bulk solution, as well as thermal denaturation, aggregation state, and biological activity when formulated for long-time storage. RESULTS: PP5ar06007 revealed as a highly homogeneous, monomeric, well-folded preparation of rPhl p 5.0109, as documented by mass spectrometry, SDS-PAGE, isoelectric focusing, size exclusion chromatography with light scattering, circular dichroism, and infrared spectroscopy. Upon storage at +4 degrees C, PP5ar06007 retained the monomeric state for at least 2 months. A protein quantity of 1.56 +/- 0.03 mg/ml was determined by amino acid analysis in PP5ar06007, and its biological activity was shown to be comparable to natural Phl p 5 in terms of basophil activation and T cell reactivity. CONCLUSIONS: Recombinant Phl p 5.0109 PP5ar06007 was characterized extensively at the physicochemical and immunological level. It revealed to be a highly stable, monomeric, and immunologically equivalent of its natural counterpart. PP5ar06007 is now available as European Pharmacopoeia allergen reference standard for grass pollen products. PMID- 26687026 TI - A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase. AB - Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID- 26687028 TI - Decreased Salinity and Actinide Mobility: Colloid-Facilitated Transport or pH Change? AB - Colloids have been implicated in influencing the transport of actinides and other adsorbed contaminants in the subsurface, significantly increasing their mobility. Such colloid-facilitated transport can be induced by changes in groundwater chemistry that occur, for example, when high ionic strength contaminant plumes are displaced by infiltrating rainwater. We studied the transport and mobility of Th(IV), as an analogue for Pu(IV) and other tetravalent actinides [An(IV)], in saturated columns packed with a natural heterogeneous subsurface sandy sediment. As expected, decreases in ionic strength both promoted the mobilization of natural colloids and enhanced the transport of previously adsorbed Th(IV). However, colloid-facilitated transport played only a minor role in enhancing the transport of Th(IV). Instead, the enhanced transport of Th(IV) was primarily due to the pH-dependent desorption of Th(IV) caused by the change in ionic strength. In contrast, the adsorption of Th(IV) had a marked impact on the surface charge of the sandy sediment, significantly affecting the mobility of the colloids. In the absence of Th(IV), changes in ionic strength were ineffective at releasing colloids while in the presence of Th(IV), decreases in ionic strength liberated significant concentrations of colloids. Therefore, under the conditions of our experiments which mimicked acidic, high ionic strength groundwater contaminant plumes, Th(IV) had a much greater effect on colloid transport than colloids had on Th(IV) transport. PMID- 26687029 TI - Clinical-psychological characteristics of refractory globus patients in China. AB - BACKGROUND: Refractory globus is not rare in clinical practice, but little research about it. AIMS: To investigate the clinical-psychological characteristics of patients with refractory globus. METHODS: Six hundred and nineteen globus patients were divided into the refractory globus group (n=149) and the non-refractory globus group (n=470). All subjects completed the following questionnaires: demographic characteristics, medical information, Hamilton Rating Scale of Anxiety/Depression, Pittsburgh Sleep Quality Index, Glasgow Edinburgh Throat Scale, and 36-item Short Form Health Survey. RESULTS: No significantly differences were found in demographic characteristics between the two groups, but the refractory globus group had longer disease duration and more serious symptoms. Sought healthcare more frequently but still had poorer quality of life than did the non-refractory globus group. Compared with the non-refractory globus group, the refractory globus group also had higher percentages of anxiety, depression, and sleep disorders. Positive correlations were observed between the severity of globus symptoms and HAMA, HAMD, and PSQI scores. CONCLUSIONS: Refractory globus is not rare in clinical practice and should receive more attention from patients and doctors because of its severe symptoms, long disease duration, poor quality of life, and accompanied by psychological disorders and sleep disorders. PMID- 26687030 TI - Percutaneous real-time sonoelastography as a non-invasive tool for the characterization of solid focal liver lesions: A prospective study. AB - BACKGROUND: Real-time sonoelastography is currently used for the characterization of superficial solid lesions such as thyroid and breast masses. This study evaluates the usefulness of percutaneous sonoelastography for the characterization of solid focal liver lesions. METHODS: 30 out of 43 patients with 38 known liver lesions were included in a prospective, diagnostic study. Qualitative analysis (pattern of deformation, elasticity type of liver tumour) and semi-quantitative measurements (strain ratio, hardness percentage, histogram) were evaluated. Sensitivity, specificity, positive and negative predictive values were calculated and the area under the receiver operating characteristics curve was constructed. RESULTS: Patterns A and C-D are specific of benign lesions and metastases respectively. The patterns for haemangiomas, focal nodular hyperplasia and metastases were significantly different to each other in terms of strain ratio, hardness percentage and histogram (p<0.05). A statistically significant difference (p<0.001) was observed between the median values of the 3 measured parameters for benign (1.02; 12%; 47) and malignant lesions (1.66; 65%; 20.5) respectively. The area under the receiver operating characteristics curve values for strain ratio, hardness percentage and histogram were 0.88, 0.89, and 0.86 respectively for cut-off values of 1.2, 45, and 30. CONCLUSIONS: By percutaneous sonoelastography it is possible to differentiate benign versus malignant focal liver lesions, metastases in particular, with good diagnostic performance. PMID- 26687031 TI - Axial skeletogenesis in human autosomal aneuploidies: A radiographic study of 145 second trimester fetuses. AB - Autosomal aneuploidies associate with multiple minor skeletal defects, which, in fetuses, are best appreciated post-mortem after specific anatomic preparations. The present study was aimed to define patterns of skeletal anomalies in autosomal aneuploidies at standard radiology in second trimester fetuses by comparing findings in and among genotypes and gestational ages. Aneuploid fetuses were selected for availability of radiographs of various axial and non-axial structures, mainly homeotic transformations, vertebral clefts, vertebral segmentation and ossification defects, absent/hypoplastic nasal bone, premature talar calcifications, and selected appendicular anomalies. Eighty six fetuses with trisomy 21, 39 with trisomy 18, eight with trisomy 13, six with triploidy, and six with rare autosomal aneuploidies were identified, 75.2% showing an abnormal costo-vertebral pattern, mostly cervical ribs, absence of the 12th thoracic ribs and posterior homeotic change. Clefting was observed along the entire spine, especially sagittal lumbar clefts, and coronal thoracic clefts. Four different types of vertebral clefting were identified, including type 1 (butterfly), type 2 (incomplete inferior), type 3 (incomplete superior), and type 4 (complete). Attenuation of clefting by gestational age was observed in trisomy 21 and 18. These findings define more clearly the pattern of perturbed morphogenesis in aneuploidy as a type of amplified developmental instability with pleiotropic effects on skeletogenesis. PMID- 26687032 TI - Medical management of an ovarian ectopic pregnancy: a case report. AB - BACKGROUND: Primary ovarian ectopic pregnancy is a rare type of ectopic pregnancy which has an estimated prevalence ranging from 1:7000 to 1:70,000 accounting for almost 3 % of all ectopic cases. Here we report the case of a 25-year-old woman who presented to our clinic with abdominal pain, 6 weeks' delay of menstruation and 3 days of vaginal bleeding, whose transvaginal ultrasonography showed an ectopic gestational sac with yolk sac inside, in her right ovary. This case shows that early diagnosis is very important particularly in places like the Sub Saharan region of Africa. CASE PRESENTATION: A 25-year-old African woman was referred to our clinic with 6 weeks' delay of menstruation, frequent increasing abdominal pain and 3 days of vaginal bleeding. Her general condition was good and her vital signs were normal. She felt tenderness in an abdominal examination and had a small amount of vaginal bleeding. Transvaginal ultrasonography showed an ectopic gestational sac with yolk sac inside, in her right ovary. Our final diagnosis was ectopic ovarian pregnancy and we successfully treated her with methotrexate. After 3 weeks of methotrexate administration her beta human chorionic gonadotropin was negative and a sonographic examination was completely normal. CONCLUSIONS: Ectopic ovarian pregnancy is a very important medical situation. It should be diagnosed in its early stages otherwise it could be life threatening and surgical treatment may be inevitable. Because of the importance of fertility, medical treatment is an acceptable option and can be feasible with early diagnosis. PMID- 26687033 TI - Linking a genome-wide association study signal to a LRRK2 coding variant in Parkinson's disease. AB - BACKGROUND: Genome-wide association studies have identified several loci associated with Parkinson's disease (PD). Whole-exome sequencing detects rare coding variants, but their links with PD genome-wide association study loci are unknown. Our objective was to investigate whether nonsynonymous variants in LRRK2 can explain associations at the PD-associated locus tagged by rs1994090. METHODS: We sequenced all coding exons of LRRK2 in 453 East Asian samples and evaluated linkage disequilibrium between each nonsynonymous variant and rs1994090. We then tested selected variants and haplotypes for association with PD in 13,581 East Asian samples. RESULTS: Of all the nonsynonymous variants, only p.Gly2385Arg was in moderate linkage disequilibrium with rs1994090 and was observed on haplotypes tagged by the rs1994090-C risk allele. Conditional analyses showed that associations at these 2 variants are not independent. CONCLUSIONS: LRRK2 p.Gly2385Arg can explain most if not all of the PD association at rs1994090 in East Asians, but other nonsynonymous variants are independent. (c) 2015 International Parkinson and Movement Disorder Society. PMID- 26687034 TI - Ribosome Mechanics Informs about Mechanism. AB - The essential aspects of the ribosome's mechanism can be extracted from coarse grained simulations, including the ratchet motion, the movement together of critical bases at the decoding center, and movements of the peptide tunnel lining that assist in the expulsion of the synthesized peptide. Because of its large size, coarse graining helps to simplify and to aid in the understanding of its mechanism. Results presented here utilize coarse-grained elastic network modeling to extract the dynamics, and both RNAs and proteins are coarse grained. We review our previous results, showing the well-known ratchet motions and the motions in the peptide tunnel and in the mRNA tunnel. The motions of the lining of the peptide tunnel appear to assist in the expulsion of the growing peptide chain, and clamps at the ends of the mRNA tunnel with three proteins ensure that the mRNA is held tightly during decoding and essential for the helicase activity at the entrance. The entry clamp may also assist in base recognition to ensure proper selection of the incoming tRNA. The overall precision of the ribosome machine-like motions is remarkable. PMID- 26687037 TI - Season's Greetings! PMID- 26687035 TI - Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms. AB - Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of "persister cells" were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics. PMID- 26687036 TI - Extracellular Toxoplasma gondii tachyzoites metabolize and incorporate unnatural sugars into cellular proteins. AB - Toxoplasma gondii is an obligate intracellular parasite that infects all nucleated cell types in diverse warm-blooded organisms. Many of the surface antigens and effector molecules secreted by the parasite during invasion and intracellular growth are modified by glycans. Glycosylated proteins in the nucleus and cytoplasm have also been reported. Despite their prevalence, the complete inventory and biological significance of glycosylated proteins in Toxoplasma remain unknown. In this study, we aimed to globally profile parasite glycoproteins using a bioorthogonal chemical reporter strategy. This strategy involves the metabolic incorporation of unnatural functional groups (i.e., "chemical reporters") into Toxoplasma glycans, followed by covalent labeling with visual probes or affinity tags. The two-step approach enables the visualization and identification of newly biosynthesized glycoconjugates in the parasite. Using a buffer that mimics intracellular conditions, extracellular Toxoplasma tachyzoites were found to metabolize and incorporate unnatural sugars (equipped with bioorthogonal functional groups) into diverse proteins. Covalent chemistries were used to visualize and retrieve these labeled structures. Subsequent mass spectrometry analysis revealed 89 unique proteins. This survey identified novel proteins as well as previously characterized proteins from lectin affinity analyses. PMID- 26687038 TI - Population and Health Services Research. PMID- 26687039 TI - Electronic cigarette use in France in 2014. AB - OBJECTIVES: The aim of this study was to investigate electronic cigarette use in France with a special focus on its relationship with tobacco smoking. METHODS: The 2014 Health Barometer is a telephone survey of 15,635 individuals which provides a status update regarding electronic cigarettes use in France. RESULTS: In 2014, 25.7 % of 15-75-year-olds had tried e-cigarettes. Among these, 23.4 % were current vapers (6.0 % of 15-75-year-olds). Among vapers, about half were daily vapers (2.9 % of 15-75-year-olds). Smoking prevalence was high among those who vape: 83.1 % were smokers (74.7 % were daily smokers) and 15.0 % were former smokers. Four out of five vapers considered that they had reduced their cigarette consumption through e-cigarette use. Vaping ex-smokers represented 0.9 % of 15-75 year-olds, which are approximately 400,000 people. This figure represents an initial estimate of the number of smokers who have successfully stopped smoking, at least temporarily, thanks to e-cigarettes. CONCLUSIONS: E-cigarettes in France were on the whole used by smokers. The e-cigarette could have helped several hundreds of thousands of individuals to quit smoking, at least temporarily. PMID- 26687040 TI - E-cigarettes as smoking cessation aids: a survey among practitioners in Italy. AB - OBJECTIVES: To describe experiences with and beliefs about e-cigarettes as safe and useful aids for smoking cessation among healthcare professionals providing smoking cessation services. METHODS: Using a cross-sectional design, anonymous structured questionnaires were completed by 179 healthcare professionals in public smoking cessation clinics across 20 regions in Italy. RESULTS: Service providers reported that considerably more smokers made inquiries about e cigarettes in 2014 than in 2013. The most frequent inquiries concerned the ingredients, safety and effectiveness of e-cigarettes as smoking cessation aids. Clients used e-cigarettes to quit smoking, cut down the number of conventional cigarettes smoked, have a safe alternative to smoking, and protect their health while continuing to smoke. More than 60 % of service providers reported favourable beliefs about the safety and effectiveness of e-cigarettes, and believed that e-cigarettes are as effective as other smoking cessation aids, including pharmacotherapy. CONCLUSIONS: Despite limited empirical evidence, service providers in Italy viewed e-cigarettes, as safe and effective smoking cessation aids. More concerted efforts are needed to improve knowledge about e cigarettes among service providers, to guide their clinical practice and decision making with respect to e-cigarettes. PMID- 26687041 TI - Dynamic contrast-enhanced MRI: Study of inter-software accuracy and reproducibility using simulated and clinical data. AB - PURPOSE: To test the reproducibility and accuracy of pharmacokinetic parameter measurements on five analysis software packages (SPs) for dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), using simulated and clinical data. MATERIALS AND METHODS: This retrospective study was Institutional Review Board approved. Simulated tissues consisted of pixel clusters of calculated dynamic signal changes for combinations of Tofts model pharmacokinetic parameters (volume transfer constant [K(trans) ], extravascular extracellular volume fraction [ve ]), longitudinal relaxation time (T1 ). The clinical group comprised 27 patients treated for rectal cancer, with 36 3T DCE-MR scans performed between November 2012 and February 2014, including dual-flip-angle T1 mapping and a dynamic postcontrast T1 -weighted, 3D spoiled gradient-echo sequence. The clinical and simulated images were postprocessed with five SPs to measure K(trans) , ve , and the initial area under the gadolinium curve (iAUGC). Modified Bland-Altman analysis was conducted, intraclass correlation coefficients (ICCs) and within subject coefficients of variation were calculated. RESULTS: Thirty-one examinations from 23 patients were of sufficient technical quality and postprocessed. Measurement errors were observed on the simulated data for all the pharmacokinetic parameters and SPs, with a bias ranging from -0.19 min(-1) to 0.09 min(-1) for K(trans) , -0.15 to 0.01 for ve , and -0.65 to 1.66 mmol.L(-1) .min for iAUGC. The ICC between SPs revealed moderate agreement for the simulated data (K(trans) : 0.50; ve : 0.67; iAUGC: 0.77) and very poor agreement for the clinical data (K(trans) : 0.10; ve : 0.16; iAUGC: 0.21). CONCLUSION: Significant errors were found in the calculated DCE-MRI pharmacokinetic parameters for the perfusion analysis SPs, resulting in poor inter-software reproducibility. J. Magn. Reson. Imaging 2016;43:1288-1300. PMID- 26687052 TI - Naphthalene Derivatives Induce Acyl Chain Interdigitation in Dipalmitoylphosphatidylcholine Bilayers. AB - The interdigitated phase of the lipid bilayer results when acyl chains from opposing monolayers fully interpenetrate such that the terminal methyl groups of the respective lipid chains are located at the interfacial region on the opposite sides of the bilayer. Usually, chain interdigitation is not encountered in a symmetric chain phosphatidylcholine (PC) membrane but can be induced under certain special conditions. In this article, we elucidate the contribution of small amphiphatic molecules in altering the physical properties of a symmetric chain PC bilayer membrane, which results in acyl chain interdigitation. Using small-angle X-ray scattering (SAXS), we have carried out a systematic investigation of the physical interactions of three naphthalene derivatives containing hydroxyl groups: beta-naphthol, 2,3-dihydroxynaphthalene, and 2,7 dihydroxynaphthalene, with dipalmitoylphosphatidylcholine (DPPC) bilayers. On the basis of the diffraction patterns, we have determined the temperature-composition phase diagrams of these binary mixtures. The present study not only enables us to gain insight into the role played by small molecules in altering the packing arrangement of the acyl chains of the constituting PC lipids of the bilayer but also brings to light some important features that have not yet been reported hitherto. One such feature is the stabilization of the enigmatic asymmetric ripple phase over a wide temperature and concentration range. The results presented here strongly point toward a clear correlation between chain interdigitation and the stability of the ripple phase. PMID- 26687053 TI - Crystal Structure of Human SSRP1 Middle Domain Reveals a Role in DNA Binding. AB - SSRP1 is a subunit of the FACT complex, an important histone chaperone required for transcriptional regulation, DNA replication and damage repair. SSRP1 also plays important roles in transcriptional regulation independent of Spt16 and interacts with other proteins. Here, we report the crystal structure of the middle domain of SSRP1. It consists of tandem pleckstrin homology (PH) domains. These domains differ from the typical PH domain in that PH1 domain has an extra conserved betaalphabeta topology. SSRP1 contains the well-characterized DNA binding HMG-1 domain. Our studies revealed that SSRP1-M can also participate in DNA binding, and that this binding involves one positively charged patch on the surface of the structure. In addition, SSRP1-M did not bind to histones, which was assessed through pull-down assays. This aspect makes the protein different from other related proteins adopting the double PH domain structure. Our studies facilitate the understanding of SSRP1 and provide insights into the molecular mechanisms of interaction with DNA and histones of the FACT complex. PMID- 26687054 TI - A nonequilibrium power balance relation for analyzing dissipative filament dynamics. AB - Biofilaments like F-actin or microtubules, as well as cilia, flagella, or filament bundles, are often deformed by distributed and time-dependent external forces. It is highly desirable to characterize these filaments' mechanics in an efficient way, either using a single experiment or a high throughput method. We here propose a dynamic power balance approach to study nonequilibrium filament dynamics and exemplify it both experimentally and theoretically by applying it to microtubule gliding assay dynamics. Its usefulness is highlighted by the experimental determination of the lateral friction coefficient for microtubules on kinesins. In contrast to what is usually assumed, friction is anisotropic, in a similar fashion as hydrodynamic friction. We also exemplify, by considering a microtubule buckling event, that if at least one parameter is known in advance, all other parameters can be determined by analyzing a single time-dependent experiment. PMID- 26687055 TI - Role of adhesion between asperities in the formation of elastic solid/solid contacts. AB - We investigated the formation of a contact between a smooth sphere of elastomer and a micro-patterned elastomer substrate. We focussed our attention on the transition between a contact only established at the top of the pillars, and a mixed contact with a central zone of full contact surrounded by a top contact corona, which was observed when the normal load was increased. The full contact zone always nucleated with a finite radius, and the transition appears to be a first-order transition, with a hysteresis due to the creation of an adhesive zone between the pillars. We propose to include the effect of the new inter-pillar adhesion to produce a realistic treatment of the mechanics of these complex contacts. This new approach quantitatively accounts for the evolution of the observed jump in the radius of the full contact with the geometrical parameters of the pattern. PMID- 26687056 TI - Droplets climbing a rotating helical fiber. AB - A liquid droplet is placed on a rotating helical fiber. We find that the droplet may slide down, attach or climb up the fiber. We inspect experimentally the domain of existence of these three behaviors as a function of the geometrical characteristics of the fiber, its angle relatively to the horizontal, the wetting properties of the fluid and the rotating speed of the helix. A theoretical model is proposed in order to capture the boundaries of the experimental phase diagram. PMID- 26687057 TI - Study of critical dynamics in fluids via molecular dynamics in canonical ensemble. AB - With the objective of understanding the usefulness of thermostats in the study of dynamic critical phenomena in fluids, we present results for transport properties in a binary Lennard-Jones fluid that exhibits liquid-liquid phase transition. Various collective transport properties, calculated from the molecular dynamics (MD) simulations in canonical ensemble, with different thermostats, are compared with those obtained from MD simulations in microcanonical ensemble. It is observed that the Nose-Hoover and dissipative particle dynamics thermostats are useful for the calculations of mutual diffusivity and shear viscosity. The Nose Hoover thermostat, however, as opposed to the latter, appears inadequate for the study of bulk viscosity. PMID- 26687059 TI - Apocynin ameliorates endotoxin-induced acute lung injury in rats. AB - Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of apocynin, a NADPH-oxidase (NOX) inhibitor on lipopolysaccharide (LPS)-induced ALI in rats were investigated. Male Sprague-Dawley rats were treated with apocynin (10mg/kg) intraperitoneally (i.p.) 1h before LPS injection (10mg/kg, i.p.). The results revealed that apocynin attenuated LPS-induced ALI as it decreased total protein content, lactate dehydrogenase (LDH) activity and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid (BALF), In addition, apocynin significantly increased superoxide dismutase (SOD) and reduced glutathione (GSH) activities with significant decrease in the lung malondialdehyde (MDA) content as compared to LPS group in lung tissue and decreased pulmonary artery contraction induced by LPS. It also upregulated mRNA expression of inhibitory protein kappaB-alpha (NFkappaBia) and downregulated mRNA expression of Toll-Like receptor 4 (TLR4) and decreased inflammation observed in lung tissues. Collectively, these results demonstrate the protective effects of apocynin against the LPS-induced ALI in rats through its antioxidant and antiinflammatory effect that may be attributed to the decrease in mRNA expression of TLR4 and increasing that of NFkappaBia. PMID- 26687060 TI - Symmetry-breaking in the H2@C60 endofullerene revealed by inelastic neutron scattering at low temperature. AB - The fine structure of the rotational ground state of molecular ortho-hydrogen confined inside the fullerene cage C60 is investigated by inelastic neutron scattering (INS). The INS line corresponding to transitions between the three sub levels comprising the ortho ground state to the non-degenerate para ground state was studied as a function of temperature down to 60 mK in neutron energy gain. The experiments show that at ambient pressure the three ortho sub-levels are split into a low energy non-degenerate level and a high energy doubly degenerate level separated by 0.135 +/- 0.010 meV. This observation is consistent with hydrogen molecules being located at sites with axial symmetry superseding the icosahedral symmetry of isolated rigid C60 cages in the solid phase. To gain insight into the role of inter-cage interactions in determining the symmetry breaking potential, the effects of hydrostatic pressure on the fine structure of the line was also investigated. The analysis of the INS spectra shows that the potential and the energy levels of H2 are sensitive to the orientation of neighbouring cages, consistent with the low-temperature crystalline phase of C60. PMID- 26687058 TI - Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients. AB - BACKGROUND: Little is known about stopping rules of nucelos(t)ide analog (NA) treatment for chronic hepatitis B (CHB). METHODS: A total of 113 consecutive patients with CHB (45 HBeAg-positive and 68 HBeAg-negative CHB patients), who met the cessation criteria of NA treatment as per the Asian-Pacific Association for the Study of the Liver (APASL) guideline, were enrolled in this prospective cohort study. The primary endpoint was to evaluate virological relapse (VR) rate within 1 year, which was defined as reappearance of hepatitis B virus (HBV)-DNA > 2000 IU/mL after cessation of NA treatment. In this cohort, entecavir was used in 81 (71.7 %) and lamivudine in 32 (28.3 %) patients. RESULTS: Within 1 year after NA treatment, VR occurred in 26 (57.8 %) HBeAg-positive patients and in 37 (54.4 %) HBeAg-negative patients. In univariate and subsequent multivariate analysis, age > 40 years [odds ratio (OR) 10.959; 95 % confidence interval (CI) 2.211 54.320; P = 0.003) and a pre-treatment HBV DNA level >2000,000 IU/mL (OR 9.285; 95 % CI 1.545-55.795; P = 0.036) were identified as independent risk factors for VR in HBeAg-positive patients, and age > 40 years (OR 6.690; 95 % CI 1.314 34.057; P = 0.022) and an end-of-treatment HBcrAg level >3.7 log IU/mL (OR 3.751; 95 % CI 1.187-11.856; P = 0.024) were identified in HBeAg-negative patients. During follow up, neither hepatic decompensation nor hepatocellular carcinoma (HCC) occurred, and HBV DNA suppression was achieved in all patients who received antiviral re-treatment. CONCLUSION: Our data suggested that the APASL stopping rule could be applied if a candidate was properly selected using individual risk factors. However, regular monitoring should be performed after cessation of NA treatment and long-term outcomes need to be evaluated further. PMID- 26687061 TI - Complete nucleotide sequence analysis of the norovirus GII.17: A newly emerging and dominant variant in China, 2015. AB - Norovirus is an important pathogen which accounts for majority of the viral related acute gastroenteritis. Recently, a variant of genotype GII.17 was reported to be predominant over GII.4 and accounted for several acute gastroenteritis outbreaks in Asia. In the current study, the full genome of a norovirus strain ZHITHC-12 isolated during this outbreak period in China was identified and characterized. The viral genome was 7557 nucleotides in length and a phylogenetic analysis based on full length genome sequences indicated that ZHITHC-12 belonged to GII.17 genotype. A further phylogenetic analysis based on all available polymerase and capsid sequences showed that ZHITHC-12 was in Cluster III on both phylogenetic trees and grouped with other strains also isolated during 2013 to 2015. Moreover, homology modeling analysis based on GII norovirus capsid 5BSX template revealed that substitutions, mutations, and more importantly, deletions and insertions, occurred at or near the putative epitopes and histo-blood group antigen (HBGA) binding sites in its protruding P2 domain, which might confer new antigenic or biological properties for this novel variant. In summary, the first full genome and capsid protein structure of a novel norovirus GII.17 variant isolated in China was extensively characterized. The data would be helpful not only for the epidemiology study, but also for the diagnostic tool development and effective vaccine design in the future. PMID- 26687063 TI - Biological activity and in vivo half-life of pro-activin A in male rats. AB - Mature TGF-beta proteins are used in vivo to promote bone growth, combat obesity, reverse fibrosis and pulmonary arterial hypertension, and as potential rejuvenation factors. However, the serum half-life of this family of growth factors is short (~5 min), limiting their therapeutic potential. Because TGF-beta proteins are normally secreted from cells with their prodomains attached, we considered whether these molecules could extend the in vivo half-life and activity of their respective growth factors. Using activin A as a model ligand, we initially modified the cleavage site between the pro- and mature domains to ensure complete processing of the activin A precursor. Co-immunoprecipitation studies confirmed mature activin A is secreted from cells in a non-covalent complex with its prodomain, however, the affinity of this interaction is not sufficient to suppress activin A in vitro biological activity. The plasma clearance profiles of purified pro- and mature activin A were determined over a 4 h period in adult male rats. Both activin forms demonstrated a two-phase decay, with the half-life of pro-activin A (t1/2 fast = 12.5 min, slow = 31.0 min) being greater than that of mature activin A (t1/2 fast = 5.5 min, slow = 20.3 min). Both pro- and mature activin A induced significant increases in serum follicle stimulating hormone levels after 4 h, but no differences were observed in the relative in vivo bioactivities of the two activin isoforms. Increased serum half life of activin A in the presence of its prodomain identifies a new means to increase the therapeutic effectiveness of TGF-beta proteins. PMID- 26687062 TI - Drosophila melanogaster: An emerging model of transgenerational effects of maternal obesity. AB - The prevalence of obesity in the world is endemic with one rapidly growing health concern being maternal obesity. Obesity during pregnancy increases the risk of gestational diabetes, miscarriage, and preeclampsia, while rendering offspring susceptible to developmental anomalies and long-term metabolic complications including type 2 diabetes and cardiovascular disease. Several studies in humans and rodents demonstrate a correlation between the risks of maternal overnutrition and factors such as epigenetics, mitochondrial dysfunction, insulin resistance, ER stress, and immune system disruption. At present, the molecular mechanisms connecting these factors to maternal obesity are unknown. This review focuses on the use of Drosophila melanogaster to study human metabolic diseases, including obesity, and its emerging use to elucidate the mechanisms of maternal overnutrition and the impact on offspring. PMID- 26687064 TI - High-fat diet during pregnancy and lactation impairs the cholinergic anti inflammatory pathway in the liver and white adipose tissue of mouse offspring. AB - Cholinergic anti-inflammatory pathway (CAP) prevents inflammatory cytokines production. The main was to evaluate the effect of maternal obesity on cholinergic pathway in the offspring. Female mice were subjected to either standard chow (SC) or high-fat diet (HFD) during pregnancy and the lactation period. After weaning, only male offspring from HFD dams (HFD-O) and from SC dams (SC-O) were fed the SC diet. Key proteins of the CAP were downregulated and serum TNF-alpha was elevated in the HFD-O mice. STAT3 and NF-kappaB activation in HFD-O mice ICV injected with nicotine (agonist) were lower than SC-O mice. Basal cholinesterase activity was upregulated in HFD-O mice in both investigated tissues. Lipopolysaccharide increased TNF-alpha and IL-1beta expression in the liver and WAT of SC-O mice, but this effect was greater in HFD-O mice. In conclusion these changes exacerbated cytokine production in response to LPS and contributed to the reduced sensitivity of the CAP. PMID- 26687065 TI - Conservative management of severe caustic injuries during acute phase leads to superior long-term nutritional and quality of life (QoL) outcome. AB - PURPOSE: Best clinical management of severe caustic injury is still a subject of debate. Most surgical teams consider severe caustic injury as an indication for emergency surgery. But, under certain circumstances, conservative management is feasible, avoids the need for gastrectomy, and has a low mortality rate. Postponed reconstructive surgery is usually performed several months after caustic ingestion to restore intestinal continuity or to treat stricture sequelae. This study aimed to investigate long-term nutritional and quality of life (QoL) outcomes after reconstructive surgery for high-grade esophageal and gastric caustic injury. METHODS: Twenty-one patients were assessed for biological and nutritional parameters, physical findings, and quality of life surveys at least 25 months after reconstructive surgery among patients who have required emergency surgery (n = 10) and patients who did not undergo emergency surgery (n = 11). RESULTS: After median follow-up of 74 months (after caustic ingestion) and 67 months (after reconstructive surgery), patients who avoided emergency surgery experienced faster oral diet resumption (49 vs. 157 days, p = 0.004), less weight loss (0.3 vs. 20 kg, p = 0.002), greater body fat percentage (22 vs. 18 %, p = 0.046), better nutritional and physical status (SF12 PCS 51 vs. 43, p = 0.036), and less trouble eating (EORTC QLQ-OG 25 31 vs. 56, p = 0.01). CONCLUSIONS: Our study is the first to evaluate long-term nutritional and QoL outcomes, following severe caustic injury. It demonstrates better long-term nutritional outcomes and QoL in patients suitable for initial conservative management. These results support full functional recuperation of spared organs, even severely burned. In the absence of clinical or biological signs necessitating immediate surgery, conservative management should be advocated. PMID- 26687067 TI - Altered white matter integrity in whole brain and segments of corpus callosum, in young social drinkers with binge drinking pattern. AB - Binge drinking is associated with impaired cognitive functioning, but the relationship of cognitive impairments and white matter integrity is less known. We used diffusion tensor imaging (DTI) to investigate the relationships of binge drinking, whole brain white matter integrity and cognitive performance during young adulthood (18 to 25 years), a period of continued brain development in two sessions 1 year apart. Binge drinkers (n = 20) and non-binge drinkers (n = 20) underwent DTI and completed measures of spatial working memory and motor impulsivity. Fractional anisotropy (FA), a measure derived from DTI, was estimated from whole brain and from five segments of the corpus callosum (CC): prefrontal, premotor/supplementary motor, motor, (SMA) sensory and parietal/temporal/occipital (PTO). FA was lower for binge than for non-binge men but not women at Session 1 and 2 for all measurements except for FA in the motor segment, which was significantly increased from Session 1 to Session 2. Lower FA in the prefrontal and PTO CC segments was associated with higher binge score, whereas lower FA in all five segments was associated with greater drug use in men and worse spatial working memory both in men and women. These findings extend the literature by showing that in early adulthood, binge drinking and drug use are linked with degradations in neural white matter and that compromised white matter at this period of brain development is linked with impaired cognitive functioning. PMID- 26687068 TI - YB-1 in breast cancer. Our laboratory data. PMID- 26687066 TI - The Six1 oncoprotein downregulates p53 via concomitant regulation of RPL26 and microRNA-27a-3p. AB - TP53 is mutated in 50% of all cancers, and its function is often compromised in cancers where it is not mutated. Here we demonstrate that the pro tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism that does not involve the negative regulator of p53, MDM2. Instead, Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of ribosomal protein L26 (RPL26). Mutation analysis confirms that RPL26 inhibits miR-27a binding and prevents microRNA-mediated downregulation of p53. The clinical relevance of this interaction is underscored by the finding that Six1 expression strongly correlates with decreased RPL26 across numerous tumour types. Importantly, we find that Six1 expression leads to marked resistance to therapies targeting the p53-MDM2 interaction. Thus, we identify a competitive mechanism of p53 regulation, which may have consequences for drugs aimed at reinstating p53 function in tumours. PMID- 26687069 TI - Intraductal papillary mucinous neoplasms of the pancreas with concurrent pancreatic and periampullary neoplasms. AB - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. METHODS: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. RESULTS: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. CONCLUSION: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association. PMID- 26687070 TI - The ARTMUS: a novel microfluidic CD4+ T-cell enumeration system for monitoring antiretroviral therapy in HIV patients. AB - We report on a novel and cost-effective microfluidic platform that integrates immunomagnetic separation and cell enumeration via DNA-induced bead aggregation. Using a two-stage immunocapture microdevice, 10 MUL of whole blood was processed to isolate CD4+ T-cells. The first stage involved the immuno-subtraction of monocytes by anti-CD14 magnetic beads, followed by CD4+ T-cell capture with anti CD4 magnetic beads. The super hydrophilic surface generated during polydimethylsiloxane (PDMS) plasma treatment allowed for accurate metering of the CD4+ T-cell lysate, which then interacted with silica-coated magnetic beads under chaotropic conditions to form aggregates. Images of the resulting aggregates were captured and processed to reveal the mass of DNA, which was used to back calculate the CD4+ T-cell number. Studies with clinical samples revealed that the analysis of blood within 24 hours of phlebotomy yielded the best results. Under these conditions, an accurate cell count was achieved (R(2) = 0.98) when compared to cell enumeration via flow cytometry, and over a functional dynamic range from 106-2337 cells per MUL. PMID- 26687071 TI - Diffusion tensor imaging-based assessment of white matter tracts and visual-motor outcomes in very preterm neonates. AB - INTRODUCTION: The purpose of this study was to assess the impact of brain injury on white matter development and long-term outcomes in very preterm (VPT) neonates. METHODS: Eighty-five VPT neonates (born <32/40 weeks gestational age (GA)) scanned within 2 weeks of birth were divided into three groups based on the presence of perinatal cerebral injury: (i) no injury, (ii) mild/moderate injury and (iii) severe injury. Diffusion tensor imaging (DTI) was acquired for each neonate and fractional anisotropy (FA), and diffusivity measures were calculated in the posterior limb of the internal capsule (PLIC) and optic radiation (OR). At 2 and 4 years of age, 41 and 44 children were assessed for motor and visual-motor abilities. Analyses determined the relation between GA and DTI measures, injury groups and DTI measures as well as developmental assessments. RESULTS: GA was related to all DTI measures within the PLIC bilaterally, FA in the OR bilaterally and AD in the left OR. The severely injured group had significantly different DTI measures in the left PLIC compared to the other two groups, independent of lateralization of lesions. Group differences in the left OR were also found, due to higher incidence of the white matter injury in the left hemisphere. No differences were found between groups and outcome measures at 2 and 4 years, with the exception of destructive periventricular venous haemorrhagic infarction (PVHI). CONCLUSIONS: DTI measures of the PLIC and OR were affected by injury in VPT neonates. These findings seen shortly after birth did not always translate into long-term motor and visual-motor impairments suggesting compensatory mechanisms. PMID- 26687072 TI - Massive spontaneous parasellar and retroclival subdural hematoma. PMID- 26687074 TI - Incubation Period and Early Natural History Events of the Acute Form of Paracoccidioidomycosis: Lessons from Patients with a Single Paracoccidioides spp. Exposure. AB - Several aspects of the natural history of paracoccidioidomycosis are still poorly understood. Different from the most prevalent, chronic form of the disease, the acute form represents a continuum from the initial respiratory infection to the full-blown disease, thus providing an opportunity to elucidate the pathogenesis of the early phase of this mycosis. We describe, for the first time, two patients with a single time point exposure to Paracoccidioides spp., for whom we were able to determine the time lapsed between exposure to the fungus Paracoccidioides spp. and the onset of signs and symptoms. In case 1, the pulmonary infection was unapparent, and the first manifestations of the acute/subacute form of the disease presented 4 months after Paracoccidioides spp. EXPOSURE: In case 2, self limited, non-specific respiratory and systemic symptoms presented 45 days after infection. Thus, our patients confirm that, within a few weeks of infection, Paracoccidioides spp. affects the pulmonary lymphatic system and initially causes no or mild-to-moderate self-limited symptoms, eventually causing abnormalities on a chest X-ray, all of which spontaneously subside. These cases provide some insight into the natural history of this mycosis, the extent of the host exposure to the fungus, and the determination of its incubation period. PMID- 26687073 TI - Fungal Mycotic Aneurysm of the Internal Carotid Artery Associated with Sphenoid Sinusitis in an Immunocompromised Patient: A Case Report and Review of the Literature. AB - In immunocompromised patients, invasive molds such as Aspergillus and Mucor can lead to locally aggressive angioinvasive infections that are often life threatening. A particularly devastating complication is the development of a fungal mycotic aneurysm resulting from invasion of the arterial wall. Due to anatomic contiguity, the sphenoid sinus provides potential access for these fungi, which often colonize the respiratory sinuses, into the cavernous sinus and internal carotid artery (ICA), thus leading to the formation of ICA aneurysms. The ideal treatment of fungal ICA aneurysms includes a combination of surgical debridement and long-term effective antifungal therapy, but the role of endoscopic resection and the duration of antimicrobials are poorly defined. Here, we present the case of a 71-year-old immunocompromised patient who developed an ICA mycotic aneurysm, associated with a proven invasive fungal infection (presumptively Mucorales) of the sphenoid sinuses, as defined by EORTC/MSG criteria, and who survived after undergoing coil embolization with parent vessel sacrifice of the aneurysm in combination with liposomal amphotericin B. We also review the literature for published cases of invasive fungal sphenoid sinusitis associated with mycotic aneurysms of the ICA and provide a comparative analysis . PMID- 26687075 TI - A Real-Time PCR Assay Based on 5.8S rRNA Gene (5.8S rDNA) for Rapid Detection of Candida from Whole Blood Samples. AB - The prevalence of Candida in bloodstream infections (BSIs) has increased. To date, the identification of Candida in BSIs still mainly relies on blood culture and serological tests, but they have various limitations. Therefore, a real-time PCR assay for the detection of Candida from whole blood is presented. The unique primers/probe system was designed on 5.8S rRNA gene (5.8S rDNA) of Candida genus. The analytical sensitivity was determined by numbers of positive PCRs in 12 repetitions. At the concentration of 10(1) CFU/ml blood, positive PCR rates of 100 % were obtained for C. albicans, C. parapsilosis, C. tropicalis, and C. krusei. The detection rate for C. glabrata was 75 % at 10(1) CFU/ml blood. The reaction specificity was 100 % when evaluating the assay using DNA samples from clinical isolates and human blood. The maximum CVs of intra-assay and inter-assay for the detection limit were 1.22 and 2.22 %, respectively. To assess the clinical applicability, 328 blood samples from 82 patients were prospectively tested and real-time PCR results were compared with results from blood culture. Diagnostic sensitivity of the PCR was 100 % using as gold standard blood culture, and specificity was 98.4 %. Our data suggest that the developed assay can be used in clinical laboratories as an accurate and rapid screening test for the Candida from whole blood. Although further evaluation is warranted, our assay holds promise for earlier diagnosis of candidemia. PMID- 26687076 TI - Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms. AB - The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed. PMID- 26687077 TI - The novel semi-biodegradable interpenetrating polymer networks based on urethane dimethacrylate and epoxy-polyester components as alternative biomaterials. AB - PURPOSE: This paper presents the pilot study aimed at the development of new full interpenetrating polymer networks based on urethane- dimethacrylate and biodegradable epoxy-polyester as the proposition of new biomaterials with gradually emerging porosity. METHODS: The urethane-dimethacrylate monomer was obtained from 4,4'-methylenebis(phenyl isocyanate) and tetraethylene glycol monomethacrylate. The redox-initiating system was employed for its radical polymerization. The epoxy-polyester was produced by oxidation of the polyester, synthesized from succinic anhydride and allyl glicydyl ether. It was cured in a step-growth process with biogenic, aliphatic amine - spermidine. The mixtures of both monomers with adequate curing agents were room temperature polymerized. The hardened materials were characterized for damping behavior and dynamic modulus, hardness, water sorption, the course of hydrolytic degradation as well as the morphology - before and during the degradation process. RESULTS: The cured materials revealed the nonporous, dense morphology. In the hydrolytic environment, the epoxy-polyester network degraded and the porous urethane dimethacrylate scaffold remained. The epoxy-polyester appeared to prevent the urethane-dimethacrylate from attaining a high degree of conversion, even if the polymerization rate and the molecular mobility of the latter one are higher than those of the epoxy-polyester. The most homogeneous material with the best physico mechanical properties was obtained when the urethane-dimethacrylate content was smaller than the epoxy-polyester content, respectively 25 and 50 wt%. CONCLUSIONS: The system presented in this work could be useful in tissue engineering, where at the beginning of the tissue regeneration process it would meet the implant mechanical properties and then would deliver its porosity, facilitating the tissue regeneration process. PMID- 26687078 TI - Topographical relationships of intramuscular nerves and vessels of the motor endplates in the thigh and gluteal regions of human fetuses: an immunohistochemical study. AB - PURPOSE: The aim of this study was to describe topography of vessels and nerves in striated muscles to understand individual muscle function. MATERIALS AND METHODS: Immunohistochemistry for nerve and artery was used to examine the thigh and gluteal muscles of six human midterm fetuses. RESULTS: The supplying nerves often accompanied arteries along epimysium bundling muscle fibers as well as in the covering fascia surrounding the entire muscle mass. However, courses of nerve twigs were usually independent of those of vessels in muscle bundles. Notably, irrespective of whether or not the vascular bundle accompanied the nerves at the muscle surface or hilus, most of the motor endplate bands did not accompany the vessels. CONCLUSION: Since the motor endplates were low vascularised, a chemical induction of vessels for nerve terminal development (or the reversed induction) seemed unlikely in striated muscles. In contrast to proprioceptive neuromuscular facilitation, manual stimulation of the endplate bands may stimulate muscle activity without sympathetic reflexes through vessel-accompanying nerves. PMID- 26687080 TI - Traditional grain alcohol (bai jiu, [Symbol: see text]) production and use in rural central China: implications for public health. AB - BACKGROUND: An estimated 25% of the alcohol consumed in China is traditional unrecorded alcohol produced and distributed informally. Consequently there is concern about its safety and its contribution to public health risk. Little has been written about this type of alcohol in China. METHODS: Researchers observed the manufacture of traditional bai jiu in a rural area of Hubei Province, Central China. Two hundred fifty-nine individuals were interviewed, either individually or in small groups, about their use of and attitudes toward bai jiu. Individuals who made or sold bai jiu were interviewed about local production, distribution, and sale. Key community leaders were asked about risks from local bai jiu production, sale, and use. RESULTS: All of the bai jiu makers followed the same basic traditional procedure. Most had learned their craft from a family member or by apprenticeship, and their product was sold to neighbors or nearby villagers. Bai jiu makers typically had a business license and a health certificate. The shops that bought and sold traditional bai jiu were family-run businesses that sold both traditional bai jiu and commercial alcohol to clientele within a close social network. Alcohol (all types) was consumed by 79.9% of interviewed villagers (89.7% of males, 50.0% of females). Of the 207 drinkers in the sample, 72.9% drank bai jiu, 59.4% drank beer, and 22.7% drank commercial spirits. Bai jiu was most often consumed at mealtimes. Bai jiu drinkers believed moderate drinking was healthy and that drinking improved the social atmosphere, and about one-third of them believed drinking too much could result in quarrels and family problems. The bai jiu business provided two sources of income for makers because spent grain from the distillation process could be fed to livestock. CONCLUSIONS: Production, sale, and use of traditional bai jiu occurred within the context of local traditions, values, customs, and social networks. The data did not suggest any significant issues related to contamination. Drinking patterns were similar to those found in other studies of alcohol use in China. Bai jiu was sold mainly to middle-aged or older men, suggesting bai jiu production and use could gradually disappear without intervention. PMID- 26687079 TI - Possum-A Framework for Three-Dimensional Reconstruction of Brain Images from Serial Sections. AB - Techniques based on imaging serial sections of brain tissue provide insight into brain structure and function. However, to compare or combine them with results from three dimensional imaging methods, reconstruction into a volumetric form is required. Currently, there are no tools for performing such a task in a streamlined way. Here we propose the Possum volumetric reconstruction framework which provides a selection of 2D to 3D image reconstruction routines allowing one to build workflows tailored to one's specific requirements. The main components include routines for reconstruction with or without using external reference and solutions for typical issues encountered during the reconstruction process, such as propagation of the registration errors due to distorted sections. We validate the implementation using synthetic datasets and actual experimental imaging data derived from publicly available resources. We also evaluate efficiency of a subset of the algorithms implemented. The Possum framework is distributed under MIT license and it provides researchers with a possibility of building reconstruction workflows from existing components, without the need for low-level implementation. As a consequence, it also facilitates sharing and data exchange between researchers and laboratories. PMID- 26687081 TI - "Mouse Clone Model" for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells. AB - To investigate the immune-rejection and tumor-formation potentials of induced pluripotent stem cells and other stem cells, we devised a model-designated the "Mouse Clone Model"-which combined the theory of somatic animal cloning, tetraploid complementation, and induced pluripotent stem cells to demonstrate the applicability of stem cells for transplantation therapy. PMID- 26687082 TI - Myocardial dysfunction in patients with aortic stenosis and hypertensive heart disease assessed by MR tissue phase mapping. AB - PURPOSE: To identify abnormalities of myocardial velocities in patients with left ventricular pressure overload using magnetic resonance tissue phase mapping (TPM). MATERIAL AND METHODS: Thirty-three patients (nine with hypertensive heart disease [HYP], 24 with aortic stenosis [AS]) and 41 healthy controls were enrolled. To assess left ventricular motion, a basal, midventricular, and apical slice were acquired using three-directional velocity-encoded phase-contrast MR with a 3T system. Target parameters were peak longitudinal (Vz ) and radial (Vr ) velocity in systole and diastole (Peaksys , Peakdias ). Analysis was done on each myocardial segment. In a subgroup (n = 7 HYP, n = 12 AS, n = 24 controls), measurement was repeated during handgrip exercise. RESULTS: AS had significantly lower Vz -Peaksys in the inferolateral and inferoseptal wall (P = 0.003-0.029) and Vr -Peaksys in the septum and anterior wall (P = 0.001-0.013) than controls. Vz -Peakdias and Vr -Peakdias were lower in AS than in controls in almost all segments (P < 0.001-0.028). HYP showed reduced Vz -Peakdias compared to controls in all basal segments as well as in the lateral midventricular wall (P < 0.001 0.045), and reduced Vr -Peakdias compared to controls predominantly in the midventricular and apical segments (P = 0.004-0.042). AS patients with focal fibrosis had significantly reduced myocardial velocities (P = 0.001-0.047) in segments without late enhancement. During exercise, Vz -Peaksys , Vr -Peaksys , and Vz -Peakdias remained unchanged in AS and HYP, but decreased in the lateral wall in controls (P < 0.001-0.043). CONCLUSION: Even with preserved left ventricle (LV) ejection fraction, peak longitudinal and radial velocities of the LV are reduced in AS and HYP, indicating early functional impairment. J. Magn. Reson. Imaging 2016;44:168-177. PMID- 26687083 TI - Effects of metal-contaminated soils on the accumulation of heavy metals in gotu kola (Centella asiatica) and the potential health risks: a study in Peninsular Malaysia. AB - Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended. PMID- 26687084 TI - Using recent high-frequency surveys to reconstitute 35 years of organic carbon variations in a eutrophic lowland river. AB - Concentrations of dissolved and particulate organic carbon (DOC and POC), total suspended solids (TSS), were measured daily, and phytoplankton pigments (chlorophyll-a and pheopigments) were measured every 3 days at three strategic stations along the eutrophic Loire River between November 2011 and November 2013 marked by a high annual and seasonal variability in hydrological regimes. This unique high-frequency dataset allowed to determine the POC origin (autochthonous or allochthonous). Some strong relationships were evidenced between POC, total pigments and TSS and were tested on a long-term database with a lower frequency (monthly data) to reconstitute unmeasured algal and detrital POC concentrations and estimate annual total organic carbon (TOC) fluxes from 1980 onwards. The results were subjected to only ~25 % uncertainty and showed that the annual TOC fluxes at the outlet of the Loire River decreased from 520 10(3) tC year(-1) (i.e. 4.7 t km(-2) year(-1)) in the early 1990s to 150 10(3) tC year(-1) (i.e. 1.4 t km(-2) year(-1)) in 2012. Although DOC always dominates, the autochthonous POC represented 35 % of the TOC load at the basin outlet by the end of the 1980s and declined to finally represent 15 % only of the TOC. The control of phosphorus direct inputs and the invasion by Corbicula clams spp. which both occurred since the early 1990s probably highly reduced the development of phytoplankton. Consequently, the autochthonous POC contribution declined and TSS concentrations in summertime significantly decreased as well as a result of both less phytoplankton and less calcite precipitation. At the present time, at least 75 % of the POC has allochthonous origins in the upper Middle Loire but downstream, autochthonous POC dominates during summer phytoplanktonic blooms when total pigments concentrations reach up to 70 MUg L(-1) (equivalent to 75 % of the total POC). PMID- 26687085 TI - The spatial-temporal variations of water quality in controlling points of the main rivers flowing into the Miyun Reservoir from 1991 to 2011. AB - Cluster analysis (CA), discriminant analysis (DA), and principal component analysis/factor analysis (PCA/FA) were used to analyze the interannual, seasonal, and spatial variations of water quality from 1991 to 2011 in controlling points (Xinzhuang Bridge, Daguan Bridge) of the main rivers (Chaohe River, Baihe River) flowing into the Miyun Reservoir. The results demonstrated that total nitrogen (TN) and total phosphorus (TP) exceeded China National Standard II for surface water separately 5.08 times and 1 time. CA showed that the water quality could be divided into three interannual (IA) groups: IAI (1991-1995, 1998), IAII (1996 1997, 1999-2000, 2002-2006), and IAIII (2001, 2007-2011) and two seasonal clusters: dry season 1 (December), dry season 2 (January-February), and non-dry season (March-November). At interannual scale, the higher concentration of SO4 (2 ) from industrial activities, atmospheric sedimentation, and fertilizer use in IAIII accelerated dissolution of carbonate, which increased Ca(2+), Mg(2+), total hardness (T-Hard), and total alkalinity (T-Alk). The decreasing trend of CODMn contributed to the establishment of sewage treatment plants and water and soil conservation in the Miyun upstream. The changing trend of NO3 (-)-N indicated increasing non-point pollution load of IAII and effective non-point pollution controlling of IAIII. Only one parameter T in the seasonal scale verified improved non-point pollution controlling. The major pollution in two controlling points was NO3 (-)-N, T-Hard, TN, and other ion pollution (SO4 (2-), F(-), Ca(2+), Mg(2+), T-Hard, T-Alk). Higher concentration of NO3 (-)-N in Xinzhuang and CODMn in Daguan indicated different controlling measures, especially controlling agriculture intensification in Chaohe River to decrease N pollution and decreasing water and soil loss and cage culture in Baihe River to weaken organic pollution. Controlling SO4 (2-) from industrial activity, atmospheric sedimentation and fertilizer use in watershed can effectively control Ca(2+), Mg(2+), T-Hard, and T-Alk. PMID- 26687086 TI - Investigation of temporal change in glacial extent of Chitral watershed using Landsat data. AB - Glaciers are also known as solid reservoirs, and in this regard, Pakistan is a blessed country to have enriched glaciers. The change in glacial extent becomes very crucial for rivers whose discharges are associated with glacier melt. Even a little change in the glacial extent may bring a significant change in the resulting river flows. Considering climate change scenarios, many researchers have predicted future flows in such catchments. But in almost all such studies, the reduction in the glaciers is not normally based on any rational. Therefore, research is needed in order to estimate how glaciers are actually behaving under the change of temperature and precipitations to better estimate the future flows. For this purpose, Chitral watershed was considered as the study area. The seasonal change in the snow extent was estimated by using MODIS data for various years that helped to identify the month with minimum glacial extent. With the help of remote sensing, unsupervised classification was performed to estimate the glacier area in Chitral watershed. The results show a definite receding trend with respect to time in the glaciers of the region for the past decade. PMID- 26687087 TI - GIS-based groundwater potential mapping using boosted regression tree, classification and regression tree, and random forest machine learning models in Iran. AB - Groundwater is considered one of the most valuable fresh water resources. The main objective of this study was to produce groundwater spring potential maps in the Koohrang Watershed, Chaharmahal-e-Bakhtiari Province, Iran, using three machine learning models: boosted regression tree (BRT), classification and regression tree (CART), and random forest (RF). Thirteen hydrological-geological physiographical (HGP) factors that influence locations of springs were considered in this research. These factors include slope degree, slope aspect, altitude, topographic wetness index (TWI), slope length (LS), plan curvature, profile curvature, distance to rivers, distance to faults, lithology, land use, drainage density, and fault density. Subsequently, groundwater spring potential was modeled and mapped using CART, RF, and BRT algorithms. The predicted results from the three models were validated using the receiver operating characteristics curve (ROC). From 864 springs identified, 605 (~70 %) locations were used for the spring potential mapping, while the remaining 259 (~30 %) springs were used for the model validation. The area under the curve (AUC) for the BRT model was calculated as 0.8103 and for CART and RF the AUC were 0.7870 and 0.7119, respectively. Therefore, it was concluded that the BRT model produced the best prediction results while predicting locations of springs followed by CART and RF models, respectively. Geospatially integrated BRT, CART, and RF methods proved to be useful in generating the spring potential map (SPM) with reasonable accuracy. PMID- 26687088 TI - Comparison of fish and macroinvertebrates as bioindicators of Neotropical streams. AB - The biomonitoring of aquatic ecosystems in developing countries faces several limitations, especially related to gathering resources. The present study aimed at comparing the responses of fish and benthic macroinvertebrates to environmental change, to identify which group best indicates the differences between reference and impacted streams in southern Brazil. We determined reference and impacted sites based on physical and chemical variables of the water. For the analysis and comparison of biological responses, we calculated 22 metrics and submitted them to a discriminant analysis. We selected from this analysis only six metrics, which showed that the two studied assemblages respond differently to environmental change. A larger number of metrics were selected for macroinvertebrates than for fish in the separate analysis. The metrics selected for macroinvertebrates in the pooled analysis (i.e., fish and macroinvertebrates together) were different from those selected in the separate analysis for macroinvertebrates alone. However, the metrics selected for fish in the pooled analysis were the same selected in the separate analysis for fish alone. The macroinvertebrate assemblage was more effective for distinguishing reference from impacted sites. We suggest the use of macroinvertebrates as bioindicators of Neotropical streams, especially in situations in which time and money are short. PMID- 26687089 TI - Quantifying specific capacity and salinity variability in Amman Zarqa Basin, Central Jordan, using empirical statistical and geostatistical techniques. AB - Modeling groundwater properties is an important tool by means of which water resources management can judge whether these properties are within the safe limits or not. This is usually done regularly and in the aftermath of crises that are expected to reflect negatively on groundwater properties, as occurred in Jordan due to crises in neighboring countries. In this study, specific capacity and salinity of groundwater of B2/A7 aquifer in Amman Zarqa Basin were evaluated to figure out the effect of population increase in this basin as a result of refugee flux from neighboring countries to this heavily populated basin after Gulf crises 1990 and 2003. Both properties were found to exhibit a three parameter lognormal distribution. The empirically calculated beta parameter of this distribution mounted up to 0.39 m(3)/h/min for specific capacity and 238 ppm for salinity. This parameter is suggested to account for the global changes that took place all over the basin during the entire period of observation and not for local changes at every well or at certain localities in the basin. It can be considered as an exploratory result of data analysis. Formal and implicit evaluation followed this step using structural analysis and construction of experimental semivariograms that represent the spatial variability of both properties. The adopted semivariograms were then used to construct maps to illustrate the spatial variability of the properties under consideration using kriging interpolation techniques. Semivariograms show that specific capacity and salinity values are spatially dependent within 14,529 and 16,309 m, respectively. Specific capacity semivariogram exhibit a nugget effect on a small scale (324 m). This can be attributed to heterogeneity or inadequacies in measurement. Specific capacity and salinity maps show that the major changes exhibit a northwest southeast trend, near As-Samra Wastewater Treatment Plant. The results of this study suggest proper management practices. PMID- 26687090 TI - Mercury speciation and dispersion from an active gold mine at the West Wits area, South Africa. AB - Total mercury (HgTOT), inorganic mercury (IHg), and methylmercury (MHg) were determined in dry season waters, sediments, and tailings from an active mine which has long history of gold exploitation. Although HgTOT in waters was generally low (0.03 to 19.60 ng L(-1)), the majority of the samples had proportions of MHg of at least 90 % of HgTOT which denotes a substantial methylation potential of the mine watersheds. Mercury was relatively high in tailing materials (up to 867 MUg kg(-1)) and also in the mine sediments (up to 837 MUg kg(-1)) especially in samples collected near tailing storage facilities and within a receiving water dam. Sediment profiles revealed mercury enrichment and enhanced methylation rate at deeper layers. The presence of IHg and decaying plants (organic matter) in the watersheds as well as the anoxic conditions of bulk sediments are believed to be some of the key factors favoring the mercury methylation at the site. PMID- 26687091 TI - Integration of land use and land cover inventories for landscape management and planning in Italy. AB - There are both semantic and technical differences between land use (LU) and land cover (LC) measurements. In cartographic approaches, these differences are often neglected, giving rise to a hybrid classification. The aim of this paper is to provide a better understanding and characterization of the two classification schemes using a comparison that allows maximization of the informative power of both. The analysis was carried out in the Molise region (Central Italy) using sample information from the Italian Land Use Inventory (IUTI). The sampling points were classified with a visual interpretation of aerial photographs for both LU and LC in order to estimate surfaces and assess the changes that occurred between 2000 and 2012. The results underscore the polarization of land use and land cover changes resulting from the following: (a) recolonization of natural surfaces, (b) strong dynamisms between the LC classes in the natural and semi natural domain and (c) urban sprawl on the lower hills and plains. Most of the observed transitions are attributable to decreases in croplands, natural grasslands and pastures, owing to agricultural abandonment. The results demonstrate that a comparison between LU and LC estimates and their changes provides an understanding of the causes of misalignment between the two criteria. Such information may be useful for planning policies in both natural and semi natural contexts as well as in urban areas. PMID- 26687092 TI - Identification of Cattle-Derived Volatiles that Modulate the Behavioral Response of the Biting Midge Culicoides nubeculosus. AB - Identification of host-derived volatiles is an important step towards the development of novel surveillance and control tools for Culicoides biting midges. In this study, we identified compounds from headspace collections of cattle hair and urine that modulate the behavioral response of Culicoides nubeculosus, a research model species with a similar host-range as the vectors of Bluetongue disease and Schmallenberg disease in Europe. Combined gas chromatography and electroantennographic detection (GC-EAD) analysis revealed 23 bioactive compounds, of which 17, together with octanal, were evaluated in a two-choice behavioral assay in the presence of CO2. Decanal, 2-phenylethanal, 1-octen-3-ol, 2-ethylhexanol, 3-methylindole, phenol, and 3-ethylphenol elicited attraction of host seeking C. nubeculosus, whereas heptanal, octanal, nonanal, 3-propylphenol, and 4-propylphenol inhibited the insects' attraction to CO2, when compared to CO2 alone. 6-Methyl-5-hepten-2-one, 3-methylphenol, 4-methylphenol, and 4-ethylphenol elicited both attraction and inhibition. The behavioral responses were dependent on the concentration tested. Our results show that cattle-derived odors have the potential to be used for the manipulation of the behavior of Culicoides biting midges. PMID- 26687093 TI - Using Peer-Referral Chains with Incentives to Promote HIV Testing and Identify Undiagnosed HIV Infections Among Crack Users in San Salvador. AB - In El Salvador, crack users are at high risk for HIV but they are not targeted by efforts to promote early HIV diagnosis. We evaluated the promise of peer-referral chains with incentives to increase HIV testing and identify undiagnosed HIV infections among networks of crack users in San Salvador. For 14 months, we offered HIV testing in communities with a high prevalence of crack use. For the following 14 months, we promoted chains in which crack users from these communities referred their peers to HIV testing and received a small monetary incentive. We recorded the monthly numbers of HIV testers, and their crack use, sexual risk behaviors and test results. After launching the referral chains, the monthly numbers of HIV testers increased significantly (Z = 6.90, p < .001) and decayed more slowly (Z = 5.93, p < .001), and the total number of crack-using testers increased nearly fourfold. Testers in the peer-referral period reported fewer HIV risk behaviors, but a similar percentage (~5 %) tested HIV positive in both periods. More women than men received an HIV-positive diagnosis throughout the study (chi(2)(1, N = 799) = 4.23, p = .040). Peer-referral chains with incentives can potentially increase HIV testing among networks of crack users while retaining a focus on high-risk individuals. PMID- 26687094 TI - Changing patterns in the surgical management of renal masses. AB - OBJECTIVE: To describe the temporal trends in surgical techniques for the management of renal masses at a single Spanish academic institution and identify factors associated with partial nephrectomy (PN) decision. MATERIALS AND METHODS: A total of 646 patients were treated by surgery for clinically localised renal masses from January 2004 to December 2012 at a tertiary referral center. Surgical techniques included open radical nephrectomy (RN), open PN, laparoscopic RN, and laparoscopic PN. Descriptive statistics were used to compare baseline characteristics and proportions of patients treated by different surgical techniques. Annual trends in the proportion of procedures performed were determined. Adjusted odds ratios (OR) and 95% confidence intervals were calculated to evaluate clinical variables predictive of PN. RESULTS: During the 9 year study period, the proportion of PN relative to RN increased from 21% to 55%. With regard to surgical approach, open procedures for both RN and PN decreased gradually in favor of minimally invasive approaches (83% in 2004 to 4% in 2011 2012). While median tumor size did not significantly change over the study period, laparoscopic PN became the most commonly performed kidney procedure in 2011-2012 (49% of all procedures). Clinical variables independently predictive of partial nephrectomy were ASA score, baseline renal function and tumor size (all P<.05). CONCLUSIONS: At our academic institution, temporal trends in the management of renal masses have established PN as the most common surgical option. Although PN was increasingly used over the study period, a parallel increase in minimally invasive approaches for RN and PN was seen. PMID- 26687095 TI - Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells. AB - We have investigated the growth-suppressive action of epigallocatechin-3-gallate (EGCG) on human leukemia Jurkat T cells. Results show a strong correlation between the dose-dependent reduction of clonogenic survival following acute EGCG treatments and the EGCG-induced decline of the mitochondrial level of Ca(2+). The cell killing ability of EGCG was synergistically enhanced by menadione. In addition, the cytotoxic effect of EGCG applied alone or in combination with menadione was accompanied by apoptosis induction. We also observed that in acute treatments EGCG displays strong antioxidant properties in the intracellular milieu, but concurrently triggers some oxidative stress generating mechanisms that can fully develop on a longer timescale. In parallel, EGCG dose-dependently induced mitochondrial depolarization during exposure, but this condition was subsequently reversed to a persistent hyperpolarized mitochondrial state that was dependent on the activity of respiratory Complex I. Fluorimetric measurements suggest that EGCG is a mitochondrial Complex III inhibitor and indicate that EGCG evokes a specific cellular fluorescence with emission at 400nm and two main excitation bands (at 330nm and 350nm) that may originate from a mitochondrial supercomplex containing dimeric Complex III and dimeric ATP-synthase, and therefore could provide a valuable means to characterize the functional properties of the respiratory chain. PMID- 26687097 TI - A Japanese, Multicenter, Open-label, Phase 3 Study to Investigate the Safety and Efficacy of Gadobutrol for Contrast-enhanced MR Imaging of the Central Nervous System. AB - PURPOSE: Gadobutrol 1.0 M is macrocyclic gadolinium-based contrast agent for magnetic resonance imaging (MRI). This multicenter, open-label, phase 3 study aimed to investigate the efficacy and safety of gadobutrol-enhanced versus unenhanced MRI in the visualization and diagnosis of central nervous system (CNS) lesions in Japanese patients. METHODS: A total of 223 patients referred for contrast-enhanced MRI of the CNS underwent unenhanced and gadobutrol-enhanced (0.1 mmol/kg body weight) MRI. The unenhanced and combined (unenhanced and enhanced) images were evaluated by three independent readers in a blinded manner for degree of contrast enhancement, border delineation, internal morphology, and number of detected lesions (primary variables), and for primary diagnosis and diagnostic confidence. Final clinical diagnoses were established by an independent truth committee consisting of two neurosurgeons. Sensitivity, specificity, and accuracy were calculated for the detection of malignancy and the preciseness of diagnoses (secondary variables) by comparing the results obtained by the blinded readers and the truth committee. RESULTS: Gadobutrol enhancement significantly improved three visualization parameters in MR images: contrast enhancement, border delineation, and internal morphology (P < 0.0001). Non inferiority was achieved for mean number of lesions detected. Gadobutrol-enhanced imaging provided significant improvements in sensitivity and accuracy for the detection of malignant disease with no loss in specificity, and also improvements in accuracy of exact match diagnosis and diagnostic confidence. Drug-related adverse events were reported in 6 out of 223 patients (2.7%); all were non serious. CONCLUSION: Gadobutrol is an effective and well-tolerated contrast agent for MR imaging of the CNS. PMID- 26687096 TI - Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain derived neurotrophic factor (proBDNF). AB - This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ~30% Caucasians) have reduced hippocampal volume and impaired hippocampal-dependent memory function, yet the same polymorphic population shows enhanced cognitive recovery after traumatic brain injury, delayed cognitive dysfunction during aging, and lower risk of late-onset Alzheimer's disease (AD) compared to those with the more common Val66 polymorphism. To examine the differences between the protein polymorphisms in structure, kinetics of binding to proBDNF receptors and in vitro function, we generated purified cleavage-resistant human variants. Intriguingly, we found no statistical differences in those characteristics. As anticipated, exogenous application of proBDNF Val66 to rat hippocampal slices dysregulated synaptic plasticity, inhibiting long-term potentiation (LTP) and facilitating long-term depression (LTD). We subsequently observed that this occurred via the glycogen synthase kinase 3beta (GSK3beta) activation pathway. However, surprisingly, we found that Met66 had no such effects on either LTP or LTD. These novel findings suggest that, unlike Val66, the Met66 variant does not facilitate synapse weakening signaling, perhaps accounting for its protective effects with aging. PMID- 26687098 TI - Acridine-based complex as amino acid anion fluorescent sensor in aqueous solution. AB - Novel acridine-based fluorescence sensors containing alaninol ligands, L1 and D1, were designed and synthesized. The structure of the compound was characterized by IR, (1)H NMR, (13)C NMR, MS spectra. L1 and D1 possess efficient Cu(2+) cation ON OFF selective signaling behavior based on ligand-to-metal binding mechanism at physiological pH condition. Additionally, the L1-Cu(II) and D1-Cu(II) complexes could further serve as reversible OFF-ON signaling sensing ensemble to allow ratiometric response to amino acid anion in aqueous solution. PMID- 26687099 TI - Syndromic surveillance of abortions in beef cattle based on the prospective analysis of spatio-temporal variations of calvings. AB - Our objective was to study the ability of a syndromic surveillance system to identify spatio-temporal clusters of drops in the number of calvings among beef cows during the Bluetongue epizootic of 2007 and 2008, based on calving seasons. France was partitioned into 300 iso-populated units, i.e. units with quite the same number of beef cattle. Only 1% of clusters were unlikely to be related to Bluetongue. Clusters were detected during the calving season of primary infection by Bluetongue in 28% (n = 23) of the units first infected in 2007, and in 87% (n = 184) of the units first infected in 2008. In units in which a first cluster was detected over their calving season of primary infection, Bluetongue was detected more rapidly after the start of the calving season and its prevalence was higher than in other units. We believe that this type of syndromic surveillance system could improve the surveillance of abortive events in French cattle. Besides, our approach should be used to develop syndromic surveillance systems for other diseases and purposes, and in other settings, to avoid "false" alarms due to isolated events and homogenize the ability to detect abnormal variations of indicator amongst iso-populated units. PMID- 26687100 TI - Does the fat-but-fit paradigm hold true for all-cause mortality when considering the duration of overweight/obesity? Analyzing the WATCH (Weight, Activity and Time Contributes to Health) paradigm. AB - BACKGROUND: Physical activity has been shown to attenuate the association between overweight/obesity and mortality. Much less is known, however, on how the duration of overweight/obesity potentially alters this association, which was the purpose of this study. METHODS: The 1999-2006 NHANES was used and 11,057 adults (ages 36-85) were evaluated. Eight mutually exclusive groups were created: (1) physically active, normal weight now and 10years ago; (2) physically inactive, normal weight now and 10years ago; (3) physically active, overweight/obese now but normal weight 10years ago; (4) physically inactive, normal weight now but overweight/obese 10years ago; (5) physically active, overweight/obese now but normal weight 10years ago; (6) physically inactive, overweight/obese now but normal weight 10years ago; (7) physically active, overweight/obese now and 10years ago; and (8) physically inactive, overweight/obese now and 10years ago. RESULTS: After adjustments, only those individuals that were inactive were at a significantly increased risk for all-cause mortality independent of overweight/obesity status (Groups 2, 4, 6, 8). CONCLUSION: In alignment with the Exercise is Medicine initiative(r), our results provide support for clinicians to perform routine assessments of physical activity, and to further promote physical activity among all individuals regardless of body mass status. PMID- 26687101 TI - Statin use prior to first myocardial infarction in contemporary patients: Inefficient and not gender equitable. AB - OBJECTIVES: Guidelines recommend initiating primary prevention with statins to those at highest cardiovascular risk. We assessed the gender-specific implementation and effectiveness of this risk-guided approach. METHODS: We identified 1399 consecutive patients without known cardiovascular disease or diabetes hospitalized with a first myocardial infarction (MI) in Denmark. Statin use before MI was assessed, and cardiovascular risk was calculated using SCORE (Systematic COronary Risk Evaluation). RESULTS: Among patients with first MI, 36% were women. Compared with men, they were older (mean 72 vs. 65years) but had a lower estimated risk (median 3.4% vs. 6.7%, SCORE high-risk model in the statin naive patients). Statin therapy had been initiated in 12% of women and 10% of men prior to MI. After adding 1.5mmol/L to the total cholesterol concentration of those already on statins, the estimated pre-treatment risk was much lower in women than men (median 3.8% vs. 9.2%, SCORE high-risk model), and only 29% of women would have passed the risk-based treatment threshold defined by the European guidelines (SCORE >=5%). Estimated risk and statin use correlated directly in men but not in women. Only ~5% of first MI are prevented by the current use of statins in people without diabetes. CONCLUSION: In people destined for a first MI, statin therapy is uncommon and prevents few events. Lower-risk women receive as much statins as higher risk men. This gender disparity and inefficient targeting of statins to those at highest risk indicate that risk scoring is not widely used in routine clinical practice in Denmark. PMID- 26687102 TI - Eco-friendly porous concrete using bottom ash aggregate for marine ranch application. AB - This article presents the test results of an investigation carried out on the reuse of coal bottom ash aggregate as a substitute material for coarse aggregate in porous concrete production for marine ranch applications. The experimental parameters were the rate of bottom ash aggregate substitution (30%, 50% and 100%) and the target void ratio (15%, 20% and 25%). The cement-coated granular fertiliser was substituted into a bottom ash aggregate concrete mixture to improve marine ranch applications. The results of leaching tests revealed that the bottom ash aggregate has only a negligible amount of the ten deleterious substances specified in the Ministry of Environment - Enforcement Regulation of the Waste Management Act of Republic Korea. The large amount of bubbles/air gaps in the bottom ash aggregate increased the voids of the concrete mixtures in all target void ratios, and decreased the compressive strength of the porous concrete mixture; however, the mixture substituted with 30% and 10% of bottom ash aggregate and granular fertiliser, respectively, showed an equal strength to the control mixture. The sea water resistibility of the bottom ash aggregate substituted mixture was relatively equal to that of the control mixture, and also showed a great deal of improvement in the degree of marine organism adhesion compared with the control mixture. No fatality of fish was observed in the fish toxicity test, which suggested that bottom ash aggregate was a harmless material and that the combination of bottom ash aggregate and granular fertiliser with substitution rates of 30% and 10%, respectively, can be effectively used in porous concrete production for marine ranch application. PMID- 26687103 TI - Retrospective Analysis of Synthetic Cannabinoid Metabolites in Urine of Individuals Suspected of Driving Impaired. AB - Identification and analysis of synthetic cannabinoids (SCs) in biological specimens remains an ongoing challenge for forensic toxicologists. Analytical method development is both resource and time consuming, and falls behind the illicit production of newer SCs. Distinguishing optimal metabolic targets and specific SC use is further complicated by metabolic pathway convergence between different SCs. Gaining further insight into the prevalence and psychopharmacologic role of these drugs in forensic cases, particularly in individuals suspected of driving impaired, is important. The prevalence of SC metabolites (SCMs) in suspects of impaired driving in Washington, DC between June 2012 and August 2013 was studied. A total of 526 urine samples were screened for 12 SCMs by liquid chromatography tandem mass spectrometry in separate duplicate analyses. Nineteen cases (3.6%) confirmed positive for the following SCMs: UR-144 N-pentanoic acid (n = 17;89%), JWH-073 butanoic acid (n = 3;16%), JWH-018 pentanoic acid (n = 3;16%), AM-2201 4-hydroxypentyl (n = 3;16%) and 5-fluoro PB22 3-carboxyindole (n = 1;5%). This study made use of existing analytical methodology to provide insight into the prevalence of synthetic cannabinoid use in DUID cases. Understanding the range and extent of use in these cases can provide valuable information to the forensic community. PMID- 26687104 TI - Hierarchical Navigation of Visual Attention: Orienting and Focusing Within and Between Hierarchically Structured Objects. AB - This study explored the dynamics of attentional navigation between two hierarchically structured objects. Three experiments examined a Hierarchical Attentional Navigation (HAN) hypothesis, by which attentional navigation between two visual stimuli is constrained to follow the path linking the two stimuli in a hierarchical object-based representation. Presented with two adjacent compound letter objects on each trial, participants successively identified the letter(s) at the specified hierarchical level (global or local) of the origin and destination object, respectively: local-local (Experiment 1), global-local (Experiment 2a), or local-global (Experiment 2b). The organizational complexity of the objects (2-level structure vs. 3-level structure) and their global size (large vs. small) were orthogonally manipulated. Results were generally consistent with the HAN hypothesis: overall response latency was positively related to the number of intervening levels of hierarchical object structure linking the two target levels. Hierarchical navigation was also suggested by the pattern of global size effects. The usefulness of the HAN framework for interpreting these and related findings in attention research is discussed. PMID- 26687105 TI - The "How" of Animacy Effects in Episodic Memory. AB - Animates are better remembered than inanimates. According to the adaptive view of human memory ( Nairne, 2010 ; Nairne & Pandeirada, 2010a , 2010b ), this observation results from the fact that animates are more important for survival than inanimates. This ultimate explanation of animacy effects has to be complemented by proximate explanations. Moreover, animacy currently represents an uncontrolled word characteristic in most cognitive research ( VanArsdall, Nairne, Pandeirada, & Cogdill, 2015 ). In four studies, we therefore investigated the "how" of animacy effects. Study 1 revealed that words denoting animates were recalled better than those referring to inanimates in an intentional memory task. Study 2 revealed that adding a concurrent memory load when processing words for the animacy dimension did not impede the animacy effect on recall rates. Study 3A was an exact replication of Study 2 and Study 3B used a higher concurrent memory load. In these two follow-up studies, animacy effects on recall performance were again not altered by a concurrent memory load. Finally, Study 4 showed that using interactive imagery to encode animate and inanimate words did not alter the recall rate of animate words but did increase the recall of inanimate words. Taken together, the findings suggest that imagery processes contribute to these effects. PMID- 26687106 TI - Speeded Probed Recall Is Affected by Grouping. AB - Most of the evidence from previous studies on speeded probed recall supported primacy-gradient models of serial order representation. Two experiments investigated the effect of grouping on speeded probed recall. Six-word lists, followed by a number between 1 and 6, were presented for speeded recall of the word in the position indicated by the number. Grouping was manipulated through interstimulus intervals. In both experiments, a significant Position * Grouping interaction was found in RT. It is concluded that the results are not consistent with models of order representation only based on a primacy gradient. Possible alternative representations of serial order are also discussed; a case is made for a holistic order representation. PMID- 26687108 TI - Understanding the mechanism of CO2 capture by 1,3 di-substituted imidazolium acetate based ionic liquids. AB - Efficient CO2 capture by ionic liquids needs a thorough understanding of underlying mechanisms of the CO2 interaction with ionic liquids, especially when it involves chemisorption. In this work we have systematically investigated the mechanism of CO2 capture by 1,3 di-substituted imidazolium acetate ionic liquids using density functional theory. Solvent effects are analyzed using QM/MM and QM/QM approaches with the help of molecular dynamics simulations and ONIOM methods. The investigation of different stepwise mechanisms shows that CO2 could be involved in the first step of the reaction mechanism, also a new two-step mechanism is proposed. The final stabilization step is analyzed and pointed out to be responsible for important experimentally-observed features of the reaction. PMID- 26687110 TI - A comparison of the nature and correlates of panic attacks in the context of Panic Disorder and Social Anxiety Disorder. AB - Panic attacks occurring outside of Panic Disorder are not well-understood despite their inclusion as a diagnostic specifier in the Diagnostic and Statistical Manual for Mental Disorders (DSM-5). This study compares panic attacks in the context of Panic Disorder compared to social anxiety in terms of their symptom frequency, severity, and clinical correlates. METHOD: Participants (n=404) were interviewed using the Anxiety Disorders Interview Schedule (ADIS-IV-L; Brown et al., 1994), from which we analyzed interviewer ratings of panic attacks and panic attack symptoms, as well as other demographic and clinical characteristics. RESULTS: Panic attacks in the context of Panic Disorder were characterized by a greater number and severity of symptoms compared to panic attacks in the context of Social Anxiety Disorder, and were associated with a history of traumatization, inpatient psychiatric treatment, and benzodiazepine use. Social anxiety panic attacks were associated with reduced physical health concerns. Cognitive panic attack symptoms were more prevalent in Panic Disorder and were associated with a variety of poor clinical correlates. CONCLUSIONS: Panic attacks in the context of Panic Disorder are more severe than those in social anxiety, and this may be driven by cognitive disturbances during those attacks. PMID- 26687109 TI - Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential. AB - BACKGROUND: No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue. METHODS: Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05. RESULTS: ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 <= age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 <= age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential. CONCLUSION: Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results. PMID- 26687111 TI - The clinical phenotype of early-onset isolated dystonia caused by recessive COL6A3 mutations (DYT27). AB - BACKGROUND AND PURPOSE: We recently identified mutations in the a3 (VI) collagen gene COL6A3 that cause autosomal-recessive isolated dystonia (DYT27). This article gives a detailed description of the clinical phenotype associated with this new type of dystonia. METHODS: A total of 5 recessive COL6A3 mutation carriers underwent clinical examinations, and case histories were recorded on videotape. RESULTS: Biallelic COL6A3 mutations cause isolated dystonia with interindividual heterogeneity of distribution and severity. Dystonia was generalized in 3 patients, pronounced in the cranio-cervical region, upper limbs, and trunk; segmental in 1 patient, with the neck and upper limbs affected; and focal with cervical involvement in another patient. Symptoms began in childhood, adolescence, or early adulthood, initially affecting the neck as cervical dystonia or the hand as writer's cramp. CONCLUSION: COL6A3-associated dystonia represents a newly identified autosomal-recessive entity characterized clinically by an early symptom onset with variable distribution. (c) 2015 Movement Disorder Society. PMID- 26687112 TI - Molecular Characterization of an Endometrial Endometrioid Adenocarcinoma Metastatic to a Thyroid Hurthle Cell Adenoma Showing Cancerization of Follicles. AB - Tumor-to-tumor metastasis is rare. Herein, we present a unique case of endometrial endometrioid adenocarcinoma metastatic to a thyroid Hurthle cell adenoma 9 years after initial diagnosis. On histologic examination of the thyroid, the malignant endometrioid glands and single cells (donor tumor) were dispersed within the Hurthle cell adenoma (recipient tumor). In several sections of the adenoma with still preserved microfollicular architecture, malignant endometrial adenocarcinoma cells were admixed within oncocytic adenomatous epithelium (so-called "cancerization of the follicles"). This unusual phenomenon, to our knowledge, is a novel finding in the thyroid gland. Immunohistochemistry, subsequently elicited clinical history, and morphologic comparison of the tumor in the thyroid to the primary endometrial tumor confirmed the origin of the donor tumor cells. Molecular analysis of both the metastatic and primary endometrial tumors demonstrated PIK3CA and PTEN mutations in both tumors, as is characteristic of well-differentiated endometrioid tumors of the endometrium. Amplification of chromosome 1q was detected in both sites; however, only the metastatic tumor showed loss of chromosomes 2, 9, and 22. The morphologic differential diagnosis of metastatic endometrioid adenocarcinoma in the thyroid includes columnar cell variant of papillary thyroid carcinoma (CCVPTC) arising in a preexisting adenoma, endocrine glandular atypia within an adenoma, and metastasis from other anatomic sites. Histomorphologic differences among these entities may be subtle; therefore, knowledge of and morphologic comparison with prior malignancies and immunohistochemistry can be helpful in rendering the correct diagnosis. PMID- 26687113 TI - Molecular physiology of EAAT anion channels. AB - Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by a family of five glutamate transporters, the so-called excitatory amino acid transporters (EAAT1-5). EAATs are prototypic members of the growing number of dual-function transport proteins: they are not only glutamate transporters, but also anion channels. Whereas the mechanisms underlying secondary active glutamate transport are well understood at the functional and at the structural level, mechanisms and cellular roles of EAAT anion conduction have remained elusive for many years. Recently, molecular dynamics simulations combined with simulation-guided mutagenesis and experimental analysis identified a novel anion-conducting conformation, which accounts for all experimental data on EAAT anion currents reported so far. We here review recent findings on how EAATs accommodate a transporter and a channel in one single protein. PMID- 26687114 TI - Use of Veterans Health Administration Mental Health and Substance Use Disorder Treatment After Exiting Prison: The Health Care for Reentry Veterans Program. AB - The Veterans Health Administration (VA) Health Care for Reentry Veterans (HCRV) program links veterans exiting prison with treatment. Among veterans served by HCRV, national VA clinical data were used to describe contact with VA health care, and mental health and substance use disorder diagnoses and treatment use. Of veterans seen for an HCRV outreach visit, 56 % had contact with VA health care. Prevalence of mental health disorders was 57 %; of whom 77 % entered mental health treatment within a month of diagnosis. Prevalence of substance use disorders was 49 %; of whom 37 % entered substance use disorder treatment within a month of diagnosis. For veterans exiting prison, increasing access to VA health care, especially for rural veterans, and for substance use disorder treatment, are important quality improvement targets. PMID- 26687115 TI - The microRNA-29 family in cartilage homeostasis and osteoarthritis. AB - MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family was also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFbeta1 decreased expression of miR-29a, b, and c (3p) in primary chondrocytes, whilst IL-1beta increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFkappaB, and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, and CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways. KEY MESSAGES: Expression of the miR-29 family is regulated in cartilage during osteoarthritis. SOX9 represses expression of the miR-29 family in chondrocytes. The miR-29 family is regulated by TGF-beta1 and IL-1 in chondrocytes. The miR-29 family negatively regulates Smad, NFkappaB, and canonical Wnt signalling. Several Wnt-related genes are direct targets of the miR-29 family. PMID- 26687116 TI - Anti-inflammatory Effect and Toxicology Analysis of Oral Delivery Quercetin Nanosized Emulsion in Rats. AB - PURPOSE: This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and antioxidant effects as well as its toxicity. METHODS: The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated. RESULTS: The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-kappaB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE. CONCLUSIONS: These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases. PMID- 26687117 TI - Gatekeeper role of gastroenterologists and surgeons in recognising and discussing familial colorectal cancer. AB - This study aimed to gain insight into the gatekeeper role of surgeons and gastroenterologists (including residents) during a first consultation at a tertiary gastro-intestinal centre regarding referral for genetic counselling, and to test the feasibility of a checklist for indications for referral. Consecutive patients were invited before and after introduction of a checklist, to complete a questionnaire assessing their perception of discussing cancer genetic topics. Initial consultations were audiotaped to assess the quality of this discussion by gastroenterologists and surgeons. Data on completeness of the checklist and referral were collected from medical files. No significant differences were found between the Before and After group regarding patients' reports of discussing cancer in the family (77%, n = 34 vs 89%, n = 33, p = 0.16). In 28% (n = 10) of the audiotaped consultations family history was adequately discussed, in 58% (n = 21) it was considered inadequate and in 14% (n = 5) of consultations it was not discussed at all. A checklist was present in 53% (n = 27) of the medical files. Of these, 5 (19%) were incomplete. Gastroenterologists and surgeons (in training) have difficulty in fulfilling their gatekeeper role of recognizing patients at familial risk for CRC. Although they often discuss familial cancer during the initial consultation, their exploration seems insufficient to reveal indications for referral for genetic counselling. Therefore, healthcare professionals should not only understand genetics and the importance of cancer family history, but also be effective in the communication of this subject to enable more adequate referral of patients for genetic counselling. PMID- 26687118 TI - Degree of exercise intensity during continuous chest compression in upper-body trained individuals. AB - BACKGROUND: Although chest-compression-only cardiopulmonary resuscitation (CCO CPR) is recommended for lay bystanders, fatigue is easily produced during CCO CPR. If CCO-CPR can be performed at a lower intensity of exercise, higher resistance to fatigue is expected. Since chest compression is considered to be a submaximal upper body exercise in a steady rhythm and since the unit of load for chest compression is expressed as work rate, we investigated the possibility that peak work rate of the upper body determines the level of exercise intensity during CCO-CPR. METHODS: Twelve sedentary individuals (group Se), 11 rugby players (group R), and 11 swimmers (group Sw) performed 10-min CCO-CPR, and heart rate (HR) and rating of perceived exertion (RPE) were measured as indices of exercise intensity. Multiple linear regression analysis was carried out to assess potential relationships of upper body weight, peak lumbar extension force, peak work rate, and peak oxygen uptake recorded during arm-crank exercise with HR and RPE during CCO-CPR. RESULTS: Values of peak work rate during arm-crank exercise (Peak WR-AC) in group Se, group R, and group Sw were 108 +/- 12, 139 +/- 27, and 146 +/- 24 watts, respectively. Values of the latter two groups were significantly higher than the value of group Se (group R, P < 0.01; group Sw, P < 0.001). HR during CCO-CPR increased with time, reaching 127.8 +/- 17.6, 114.8 +/- 16.5, and 118.1 +/- 14.2 bpm at the 10th minute in group Se, group R, and group Sw, respectively. On the other hand, RPE during CCO-CPR increased with time, reaching 16.4 +/- 1.4, 15.4 +/- 1.7, and 13.9 +/- 2.2 at the 10th minute in group Se, group R, and group Sw, respectively. Multiple linear regression analysis showed that only peak WR-AC affects both HR and RPE at the 10th minute of CCO-CPR (HR, r = -0.458; P < 0.01; RPE, r = -0.384, P < 0.05). CONCLUSIONS: The degree of exercise intensity during CCO-CPR is lower in individuals who have a higher peak work rate of the upper body. PMID- 26687120 TI - Chronic Management of Hypertension after Stroke: The Role of Ambulatory Blood Pressure Monitoring. AB - Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24 hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended. PMID- 26687119 TI - Sonochemical Synthesis and Characterization of the Copper(II) Nanocomplex: DNA- and BSA-Binding, Cell Imaging, and Cytotoxicity Against the Human Carcinoma Cell Lines. AB - The focus of the present work is the preparation of new metal-based nanodrug to overcome limitations of chemotherapy such as poor water solubility of most common chemotherapeutic drugs. The copper(II) complex of 1,2,4-triazine derivatives, [Cu(dppt)2(H2O)2](2+) (dppt is 5,6-diphenyl- 3- (2-pyridyl)-1,2,4-triazine), has been synthesized at nano-size by sonochemical method and characterized by FTIR, zetasizer, and scanning electron microscopy (SEM). The interaction of the complex and nanocomplex with fish sperm DNA (FS-DNA) and BSA have been investigated under physiological conditions by a series of experimental methods. The results have indicated that the complex binds to FS-DNA by two biding modes, viz., electrostatic and intercalates into the base pairs of DNA. The competitive study with ethidium bromide (EB) shows that the complex and nanocomplex competes for the DNA-binding sites with EB. Protein binding studies show that the complex and nanocomplex could bind with BSA. The results of synchronous fluorescence of BSA show that additions of the complex affect the microenvironment of both tyrosine and tryptophan residues during the binding process. The in vitro cytotoxicity of the complex (solution in DMSO) and nanocomplex (colloid in H2O) against the human carcinoma cell lines (MCF-7 and A-549) was evaluated by MTT assay. The results of in vitro cytotoxicity indicate that the complex and nanocomplex have excellent cytotoxicity activity against MCF-7 and A-549. Results of the microscopic analyses of the cancer cells confirm the results of the cytotoxicity. PMID- 26687121 TI - Changes in Painting Style by Poststroke Mania. PMID- 26687122 TI - Post-stenotic Recirculating Flow May Cause Hemodynamic Perforator Infarction. AB - BACKGROUND AND PURPOSE: The primary mechanism underlying paramedian pontine infarction (PPI) is atheroma obliterating the perforators. Here, we encountered a patient with PPI in the post-stenotic area of basilar artery (BA) without a plaque, shown by high-resolution magnetic resonance imaging (HR-MRI). We performed an experiment using a 3D-printed BA model and a particle image velocimetry (PIV) to explore the hemodynamic property of the post-stenotic area and the mechanism of PPI. METHODS: 3D-model of a BA stenosis was reconstructed with silicone compound using a 3D-printer based on the source image of HR-MRI. Working fluid seeded with fluorescence particles was used and the velocity of those particles was measured horizontally and vertically. Furthermore, microtubules were inserted into the posterior aspect of the model to measure the flow rates of perforators (pre-and post-stenotic areas). The flow rates were compared between the microtubules. RESULTS: A recirculating flow was observed from the post-stenotic area in both directions forming a spiral shape. The velocity of the flow in these regions of recirculation was about one-tenth that of the flow in other regions. The location of recirculating flow well corresponded with the area with low-signal intensity at the time-of-flight magnetic resonance angiography and the location of PPI. Finally, the flow rate through the microtubule inserted into the post-stenotic area was significantly decreased comparing to others (P<0.001). CONCLUSIONS: Perforator infarction may be caused by a hemodynamic mechanism altered by stenosis that induces a recirculation flow. 3D-printed modeling and PIV are helpful understanding the hemodynamics of intracranial stenosis. PMID- 26687123 TI - Trends in Incident and Recurrent Rates of First-Ever Ischemic Stroke in Taiwan between 2000 and 2011. AB - BACKGROUND AND PURPOSE: The burden of stroke is comparatively greater in Asian countries than in the Western world. While there has been a documented recent decline in the incidence of stroke in several Western nations due to better risk factor management, much less is known about the nature and trajectory of stroke in Asia over the last decade. The objective of this study was to explore risk factors, medication use, incidence, and one-year recurrence of stroke in Taiwan. METHODS: We conducted a nationwide cohort study by reviewing all hospitalized patients (>= 18 years) with a primary diagnosis of ischemic stroke between 2001 and 2011 from Taiwan National Health Insurance Research Database. RESULTS: A total of 291,381 first-ever ischemic stroke patients were enrolled between 2000 and 2011. The average age was about 70 years and approximately 58.6% of them were men. While prevalence of diabetes mellitus and hyperlipidemia, as well as use of statins, antiplatelet agents, and oral anticoagulant agents for atrial fibrillation significantly increased; incidence (142.3 vs. 129.5 per 100,000 in 2000 and 2011, respectively) and one-year recurrence (9.6% vs. 7.8% in 2000 and 2011, respectively) of stroke declined during this period of time. CONCLUSIONS: Over the last decade in Taiwan, rates of primary ischemic stroke and one-year recurrent stroke decreased by 9% and 18% respectively. PMID- 26687124 TI - Effect of pure muscle retraction on multifidus injury and atrophy after posterior lumbar spine surgery with 24 weeks observation in a rabbit model. AB - PURPOSE: To evaluate the effect of pure muscle retraction on multifidus injury and atrophy. MATERIALS AND METHODS: Sixty-three adult New Zealand white rabbits were divided evenly into three groups: 1-h retraction (group R1), 2-h retraction (R2), and sham surgery (C). The multifidus muscle was evaluated using magnetic resonance imaging (MRI) and histology after 3 and 48 h, and 1, 3, 6, 12, and 24 weeks after surgery. RESULTS: Multifidus muscle injury and atrophy were not observed in group C, but were obvious in groups R1 and R2. Edema, necrosis, and inflammation mainly occurred in the first week postoperatively, and were more severe in R2 than in R1 (P < 0.01). Muscle fiber regeneration began at week 1, fibrotic changes mainly occurred at weeks 3 and 6, and fat degeneration became obvious at weeks 12 and 24 postoperatively. The fibrosis and fat degeneration scores of R2 were higher than those of R1 (P < 0.01). Decreased acetylcholine activity and granular degeneration of the neuromuscular junction were observed in both retraction groups, but was more severe in R2 than in R1 (P < 0.01). CONCLUSION: Muscle retraction was an important factor not only for multifidus injury, but also for long-term multifidus atrophy after posterior lumbar surgery; a longer retraction time caused more severe multifidus injury and atrophy. Muscle fibers can be regenerated postoperatively, and denervation might be the reason for muscle atrophy. PMID- 26687125 TI - Single- versus dual-rod anterior instrumentation of thoracolumbar curves in adolescent idiopathic scoliosis. AB - PURPOSE: Single or dual-rod instrumentation can be used for the anterior fixation of the spine in adolescent idiopathic scoliosis (AIS). We aim to compare the complications, radiographic and functional outcomes of patients with AIS who have undergone single and dual-rod instrumentation. METHODS: This is a multi-centre study involving the Royal Children's, Royal Melbourne and Epworth hospitals. Three primary surgeons were involved to ensure homogeneity of surgical technique and implants. Patients with AIS and thoracolumbar curves (Lenke 5 and 6) undergoing anterior instrumentation from 1st January 2000 to 30th June 2013 were included. Radiographic data were collected from X-rays. The functional outcome was measured through the Scoliosis Research Society questionnaire (SRS-30). RESULTS: The study included 58 patients (38 single-rod and 20 dual-rod patients). Thirty-nine patients were classified with Lenke 5 curves, while 19 patients had Lenke 6 curves. Structural interbody supports were used in 95 % of cases. In the preoperative to postoperative period, patients with single rods had an improvement of 75 and 51 % for primary and secondary curves, respectively, while patients with dual rods had an improvement of 70 and 38 % for primary and secondary curves, respectively. There were no cases of pseudoarthrosis or metalware failure in either group. Two patients (one single-rod and one dual-rod patient) required further unplanned posterior fusion. 91 % of patients were satisfied with the results of their back management. CONCLUSION: Pseudoarthrosis and metalware failure are rare complications of anterior instrumentation. Our study found no significant difference in functional or radiographic outcome between single and dual-rod instrumentation. LEVEL OF EVIDENCE: Level III. PMID- 26687126 TI - Treatment outcomes of single-visit versus multiple-visit non-surgical endodontic therapy: a randomised clinical trial. AB - BACKGROUND: Clincians have been providing single-visit and multiple-visit endodontic treatments for their patients. This study aims to compare the success rate, prevalence of postoperative pain and chairside time of single-visit and multiple-visit endodontic treatments. METHOD: Patients who required primary endodontic treatment in a university dental clinic were randomly allocated to two general dentists for single-visit or multiple-visit treatments using the same materials and procedures. Ni-Ti rotary files were used to prepare the root canals, which were subsequently obturated with a core-carrier technique. The chairside time was recorded. The treated teeth were followed up every 6 months on clinically signs and symptoms including pain, tenderness to percussion, sinus tract, mobility and abscess. Periapical radiographs were taken to assess periapical pathology. Successful treatments were neither clinical signs/symptoms noted nor radiographic periapical pathology found postoperatively. RESULTS: A total of 220 teeth from patients aged 46.4 +/- 14.1 were followed up for at least 18 months. The mean (+/-SD) follow-up period was 29.4 +/- 9.3 months. The success rates of single-visit and multiple-visit treatments were 88.9 and 87.4 %, respectively (p = 0.729, effect size odds ratio = 1.156). Maxillary teeth had odds ratios of 3.16 (95 % CI: 1.33 to 7.46; p = 0.009) and absence of preoperative apical periodontitis had odds ratios of 4.35 (95 % CI: 1.43 to 13.24; p = 0.010) were identified from logistic regression as having a higher success rate. The average chairside times of single-visit and multiple-visit treatments were 62.0 and 92.9 min, respectively (mean difference = -30.9, 95 % CI: -39.4 to -22.4, p < 0.001, effect size odds ratio = -0.996). Single-visit and multiple-visit treatment had no significant difference in the prevalence of postoperative pain within 7 days (21 and 12 %, p = 0.055, effect size odds ratio = 2.061) and after at least 18 months (0.9 and 1.0 %, p > 0.999, effect size odds ratio = 0.879). CONCLUSIONS: The success rate and prevalence of postoperative pain of single-visit or multiple-visit treatment had no significant difference. The chairside time for single-visit treatment was shorter than multiple-visit treatment. TRIAL REGISTRATION: Clinical Trials (WHO) ChiCTR-IOR-15006117 registered on 20 March 2015. PMID- 26687127 TI - Membrane array and multiplex bead analysis of tear cytokines in systemic sclerosis. AB - Although serious ocular manifestations of systemic sclerosis (SSc) have been described, tear analysis of patients with SSc has not been performed in previous studies. Our aim was to measure a wide panel of cytokines and chemokines in tears of patients with SSc and to assess the most significant molecules with a more sensitive and specific method. Unstimulated tear samples were collected from nine patients with SSc and 12 age- and gender-matched healthy controls. The relative levels of 102 different cytokines were determined by a cytokine array, and then absolute levels of four key cytokines were determined by a magnetic bead assay. Array results revealed shifted cytokine profile characterized by predominance of inflammatory mediators. Of the 102 analyzed molecules, nine were significantly increased in tears of patients with SSc. Based on the multiplex bead results, C reactive protein, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 levels were significantly higher in tears of patients with SSc. Our current data depict a group of inflammatory mediators, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc patients with ocular manifestations. PMID- 26687128 TI - Spontaneous inward currents reflecting oscillatory activation of Na+/Ca2+ exchangers in human embryonic stem cell-derived cardiomyocytes. AB - Na(+)/Ca(2+) exchanger current (INCX) triggered by spontaneous Ca(2+) release from sarcoplasmic reticulum (SR) has been suggested as one of the cardiac pacemaker mechanisms ("Ca(2+) clock model"). In human embryonic stem cell-derived cardiomyocytes (hESC-CMs) showing spontaneous action potentials (APs), we found that substantial population (35 %) showed regular oscillation of inward currents (SICs) in nystatin-perforated voltage clamp between -40 and 40 mV (-80 +/- 10.6 pA, at -20 mV). SICs were similarly observed between nodal, atrial, and ventricular hESC-CMs. Oscillations of [Ca(2+)]i synchronized with SICs were observed under voltage clamp. SICs were eliminated by lowering [Ca(2+)]e, L-type Ca(2+) channel (VOCCL) blocker (nifedipine, 10 uM), ryanodine receptor (RyR) agonist (caffeine, 10 mM), or NCX inhibitor (1 uM SN-6 and 10 uM KB-R7943). Plasma membrane expression of NCX1 was confirmed using immunofluorescence confocal microcopy. Both caffeine and SN-6 slowed the pacemaker potential but did not abolish the AP generation. The inhibitors of funny current (3 uM ivabradine) or voltage-gated K(+) channel currents (1 uM E4031 and 10 uM chromanol-293B) also did not abolish but slowed the pacemaker potential. In a computational model of cardiac pacemaker by Maltsev and Lakatta (2009), after modifying the spatial distribution of RyR, VOCCL, and NCX by using our multiparameter adjust algorithm, we could successfully reproduce spontaneous SR Ca(2+) release and SICs under voltage clamp. It was proposed that, under the membrane depolarization activating VOCCL, oscillatory Ca(2+) releases via RyR induce sharp increases in subsarcolemmal [Ca(2+)]i and inward INCX (SICs). Since the hESC-CMs without SICs still showed spontaneous APs, the putative "Ca(2+) clock" would provide a redundant pacemaker or augmenting mechanism in hESC-CMs. PMID- 26687130 TI - Costs and benefits of larval jumping behaviour of Bathyplectes anurus. AB - Bathyplectes anurus, a parasitoid of the alfalfa weevils, forms a cocoon in the late larval stage and exhibits jumping behaviour. Adaptive significance and costs of the cocoon jumping have not been thoroughly studied. We hypothesised that jumping has the fitness benefits of enabling habitat selection by avoiding unfavourable environments. We conducted laboratory experiments, which demonstrated that jumping frequencies increased in the presence of light, with greater magnitudes of temperature increase and at lower relative humidity. In addition, when B. anurus individuals were allowed to freely jump in an arena with a light gradient, more cocoons were found in the shady area, suggesting microhabitat selection. In a field experiment, mortality of cocoons placed in the sun was significantly higher than for cocoons placed in the shade. B. anurus cocoons respond to environmental stress by jumping, resulting in habitat selection. In the presence of potential predators (ants), jumping frequencies were higher than in the control (no ant) arenas, though jumping frequencies decreased after direct contact with the predators. Body mass of B. anurus cocoons induced to jump significantly decreased over time than cocoons that did not jump, suggesting a cost to jumping. We discuss the benefits and costs of jumping behaviour and potential evolutionary advantages of this peculiar trait, which is present in a limited number of species. PMID- 26687132 TI - Aerobic and anaerobic enzymatic activity of orange roughy (Hoplostethus atlanticus) and alfonsino (Beryx splendens) from the Juan Fernandez seamounts area. AB - The aerobic and anaerobic enzymatic activity of two important commercial bathypelagic species living in the Juan Fernandez seamounts was analyzed: alfonsino (Beryx splendens) and orange roughy (Hoplostethus atlanticus). These seamounts are influenced by the presence of an oxygen minimum zone (OMZ) located between 160 and 250 m depth. Both species have vertical segregation; alfonsino is able to stay in the OMZ, while orange roughy remains at greater depths. In this study, we compare the aerobic and anaerobic capacity of these species, measuring the activity of key metabolic enzymes in different body tissues (muscle, heart, brain and liver). Alfonsino has higher anaerobic potential in its white muscle due to greater lactate dehydrogenase (LDH) activity (190.2 MUmol NADH min(-1) g ww(-1)), which is related to its smaller body size, but it is also a feature shared with species that migrate through OMZs. This potential and the higher muscle citrate synthase and electron transport system activities indicate that alfonsino has greater swimming activity level than orange roughy. This species has also a high MDH/LDH ratio in its heart, brain and liver, revealing a potential capacity to conduct aerobic metabolism in these organs under prolonged periods of environmental low oxygen conditions, preventing lactic acid accumulation. With these metabolic characteristics, alfonsino may have increased swimming activity to migrate and also could stay for a period of time in the OMZ. The observed differences between alfonsino and orange roughy with respect to their aerobic and anaerobic enzymatic activity are consistent with their characteristic vertical distributions and feeding behaviors. PMID- 26687131 TI - High CO2 concentration as an inductor agent to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories. AB - Cationic alpha-helical antimicrobial peptides such as BP100 are of increasing interest for developing novel phytosanitary or therapeutic agents and products with industrial applications. Biotechnological production of these peptides in plants can be severely impaired due to the toxicity exerted on the host by high level expression. This can be overcome by using inducible promoters with extremely low activity throughout plant development, although the yields are limited. We examined the use of modified atmospheres using the increased levels of [CO2], commonly used in the food industry, as the inductor agent to biotechnologically produce phytotoxic compounds with higher yields. Here we show that 30% [CO2] triggered a profound transcriptional response in rice leaves, including a change in the energy provision from photosynthesis to glycolysis, and the activation of stress defense mechanisms. Five genes with central roles in up regulated pathways were initially selected and their promoters successfully used to drive the expression of phytotoxic BP100 in genetically modified (GM) rice. GM plants had a normal phenotype on development and seed production in non-induction conditions. Treatment with 30 % [CO2] led to recombinant peptide accumulation of up to 1 % total soluble protein when the Os.hb2 promoter was used. This is within the range of biotechnological production of other peptides in plants. Using BP100 as a proof-of-concept we demonstrate that very high [CO2] can be considered an economically viable strategy to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories. PMID- 26687129 TI - Stem cell death and survival in heart regeneration and repair. AB - Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function. PMID- 26687134 TI - Alone in the Crowd: I Failed the ABGC Certification Exam. AB - The American Board of Genetic Counseling (ABGC) certification examination (often referred to as "the board exam") has become a milestone within the field of genetic counseling. For many, it is the final standardized test taken and indicates the examinee has met "the standards of minimal competence to practice as a genetic counselor" (Bulletin 2015). Although voluntary, certification is strongly encouraged, and in some employment situations, required. Although recent statistics indicate the majority of those who take the test pass, each year there are those who sit for the test unsuccessfully. Despite this fact, exam failure and tools for dealing with this experience are not often broached in the literature. This essay recalls my experiences with a failed exam attempt and the subsequent emotional turmoil. It also aims to start the conversation regarding the difficulty of coping with the "secret" shame of public, professional failure, and suggests there is room for further discussion and resource development in this area. PMID- 26687135 TI - Trimethyltin chloride inhibits neuronal cell differentiation in zebrafish embryo neurodevelopment. AB - Trimethyltin chloride (TMT) is a neurotoxicant widely present in the aquatic environment, primarily from effluents of the plastic industry. It is known to cause acute neuronal death in the limbic-cerebellar system, particularly in the hippocampus. However, relatively few studies have estimated the effects of TMT toxicity on neurodevelopment. In this study, we confirmed the dose-dependent effects of TMT on neurodevelopmental stages through analysis of morphological changes and fluorescence assays using HuC-GFP and olig2-dsRed transgenic zebrafish embryos. In addition, we analyzed the expression of genes and proteins related to neurodevelopment. Exposure of embryos to TMT for 4 days post fertilization (dpf) elicited a concentration-related decrease in body length and increase in axial malformation. TMT affected the fluorescent CNS structure by decreasing pattern of HuC-GFP and olig2-dsRed transgenic zebrafish. In addition, it significantly modulated the expression patterns of Sonic hedgehog a (Shha), Neurogenin1 (Ngn1), Embryonic lethal abnormal vision like protein 3 (Elavl3), and Glial fibrillary acidic protein (Gfap). The overexpression of Shha and Ngn1, and downregulation of Elavl3 and Gfap, indicate repression of proneural cell differentiation. Our study demonstrates that TMT inhibits specific neurodevelopmental stages in zebrafish embryos and suggests a possible mechanism for the toxicity of TMT in vertebrate neurodevelopment. PMID- 26687136 TI - From red to green: the propidium iodide-permeable membrane of Shewanella decolorationis S12 is repairable. AB - Viability is a common issue of concern in almost all microbial processes. Fluorescence-based assays are extensively used in microbial viability assessment, especially for mixed-species samples or biofilms. Propidium iodide (PI) is the most frequently used fluorescence indicator for cell viability based on the membrane permeability. Our results showed that the accumulation of succinate from fumarate respiration could induce PI-permeability in Shewanella decolorationis biofilm cells. Confocal laser scanning microscope further showed that the PI permeable membrane could be repaired in situ when the extracellular succinate was eliminated by switching fumarate respiration to electrode respiration. Simultaneously with the membrane repair, the electrode respiring capacity of the originally PI-permeable cells was recovered. Agar-colony counts suggested that a major portion of the repaired cells were viable but nonculturable (VBNC). The results evidenced that S. decolorationis S12 has the capacity to repair PI permeable membranes which suggests a reevaluation of the fate and function of the PI-permeable bacteria and expanded our knowledge on the flexibility of bacterial survival status in harsh environments. PMID- 26687137 TI - Complete Clinical Response of BRAF-Mutated Cholangiocarcinoma to Vemurafenib, Panitumumab, and Irinotecan. PMID- 26687138 TI - Association of Methylenetetrahydrafolate Reductase Gene Polymorphism (MTHFR) in Patients with Gallbladder Cancer. AB - PURPOSE: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a major role in DNA methylation. There are two popular MTHFR polymorphisms known as C677T and A1298C which are found to be involved in folate metabolism and lowering the enzyme activity, thus may be linked with cancer development. This study aims to look at the association of these polymorphisms in gallbladder cancer. METHODS: Thirty patients each with gallbladder cancer, cholelithiasis, and normal gallbladder were genotyped for the above-given polymorphisms by PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: C677T MTHFR polymorphism was not associated (chi(2) = 2.44, p = 0.85) with an increased likelihood of having gallbladder cancer. A1298C was significantly associated (chi(2) = 28.87, p < 0.001) with risk of developing gallbladder cancer. A1298C was significantly correlated with grade (r = 0.337, p < 0.001) and histopathology (r = 0.446, p < 0.001). CONCLUSION: This study proposed that MTHFR A1298C polymorphism may be associated with risk of developing gallbladder cancer, and there is no association between C677T polymorphism and gallbladder cancer. PMID- 26687139 TI - Study of the Annexin A1 and Its Associations with Carcinoembryonic Antigen and Mismatch Repair Proteins in Colorectal Cancer. AB - PURPOSE: Annexin-A1 (ANXA1) has been implicated in various tumor types, but few studies have investigated its involvement in colorectal cancer. The study aimed to analyze ANXA1 expression in the normal margin and colorectal tumor tissues of 104 patients who underwent surgery for colorectal cancer and to associate the ANXA1 expression with predictive clinicopathological variables. METHODS: Hematoxylin-eosin and immunohistochemical staining were used for the analysis. RESULTS: ANXA1 expression was higher in colorectal cancer than in normal margin tissue (p = 0.0001). However, no differences were observed when we analyzed the ANXA1 expression in colon and rectal tumors (p = 0.830). Also, this protein positivity was associated with increased carcinoembryonic antigen levels (p = 0.004). Our data in the DNA-mismatch repair proteins expression was in accordance to the literature. And their positivity was not associated with ANXA1 presence in colorectal cancer. CONCLUSION: The high incidence of ANXA1 positive expression in colorectal cancer and its association with carcinoembryonic antigen levels might indicate the importance of this protein in the colorectal cancer biology. PMID- 26687140 TI - Embedded Three-Layer Esophagogastric Anastomosis Reduces Morbidity and Improves Short-Term Outcomes After Esophagectomy for Cancer. AB - BACKGROUND: There exists great controversy regarding the use of esophagogastric anastomotic techniques in the treatment of esophageal cancer. The aim of this study was to compare two types of cervical esophagogastric anastomoses with respect to the reduction of postoperative anastomotic leaks, stenosis, and gastroesophageal reflux. METHODS: From June 2010 to September 2013, 339 patients who underwent two different cervical esophagogastric anastomotic procedures after thoracolaparoscopic esophagectomy for esophageal cancer were identified. RESULTS: A total of 166 patients with esophageal cancer were treated using an embedded three-layer anastomosis (embedded group), and 173 were treated using a conventional two-layer anastomosis (conventional group). The rates of anastomotic leak (2.4% [4 of 166] versus 7.5% [13 of 173], p = 0.031) and benign anastomotic stricture (4.8% [8 of 166] versus 12.7% [22 of 173], p = 0.010) were significantly lower in the embedded group compared with the conventional group. The mean reflux scores were significantly higher among the patients in the conventional group compared with the patients in the embedded group at 1 month (25.2 versus 19.0, p = 0.001), 3 months (27.8 versus 21.4, p = 0.001), and 6 months (23.4 versus 17.8, p < 0.001) of follow-up. The mean scores for dysphagia were significantly lower among the patients in the embedded group compared with the patients in the conventional group at both 3 months (22.7 versus 29.8, p = 0.012) and 6 months (16.0 versus 21.3, p = 0.008) of follow-up. CONCLUSIONS: The new embedded three-layer esophagogastric anastomosis offers several advantages and reduces the incidence of postoperative complications such as anastomotic leak, stricture, and gastroesophageal reflux. PMID- 26687141 TI - Pulmonary Artery Pressure and Benefit of Lung Transplantation in Adult Cystic Fibrosis Patients. AB - BACKGROUND: The effect of lung transplantation (LTx) in patients afflicted with cystic fibrosis (CF) and pulmonary hypertension (PH) at placement on the waiting list is not well studied. METHODS: To predict the relationship between initial mean pulmonary artery pressure (MPAP) and hazard ratio (HR) of death after listing associated with LTx in adult patients with CF, the United Network for Organ Sharing database was queried for the years 2005 to 2013. Survival was assessed from waiting list entry until death on the waiting list, death after LTx, or censoring. A multivariate Cox model was performed to estimate the HR of LTx conditional on MPAP at listing. RESULTS: Of 1,841 patients with CF, 10% (177) died on the waiting list, 18% (325) were censored without undergoing LTx, and 73% (1,339) underwent transplantation, 361 of whom died after transplantation. A multivariate Cox model of survival since list entry including 1,336 patients found a protective but statistically insignificant benefit of LTx for patients whose MPAP at listing was 25 mm Hg (HR, 0.879; 95% confidence interval [CI], 0.657-1.177; p = 0.388), yet LTx was predicted to be more protective at higher initial MPAP levels, as indicated by the significant interaction term between LTx and MPAP (HR, 0.953; 95% CI, 0.928-0.978; p < 0.001). The predicted LTx HR and 95% CI were protective (HR < 1) at p < 0.05 for patients with MPAP greater than or equal to 30 mm Hg at listing. CONCLUSIONS: Survival benefit of LTx in CF was increasingly protective at higher MPAP levels, with a severity level of PH established above which a survival advantage of LTx was found. PMID- 26687142 TI - From the rhetoric to the real: A critical review of how the concepts of recovery and social inclusion may inform mental health nurse advanced level curricula - The eMenthe project. AB - OBJECTIVES: This critical review addresses the question of how the concepts of recovery and social inclusion may inform mental health nurse education curricula at Master's level in order to bring about significant and positive change to practice. DESIGN: This is a literature-based critical review incorporating a rapid review. It has been said that if done well, this approach can be highly relevant to health care studies and social interventions, and has substantial claims to be as rigorous and enlightening as other, more conventional approaches to literature (Rolfe, 2008). DATA SOURCES: In this review, we have accessed contemporary literature directly related to the concepts of recovery and social inclusion in mental health. REVIEW METHODS: We have firstly surveyed the international literature directly related to the concepts of recovery and social inclusion in mental health and used the concept of emotional intelligence to help consider educational outcomes in terms of the required knowledge, skills and attitudes needed to promote these values-based approaches in practice. RESULTS: A number of themes have been identified that lend themselves to educational application. International frameworks exist that provide some basis for the developments of recovery and social inclusion approaches in mental health practice, however the review identifies specific areas for future development. CONCLUSIONS: This is the first article that attempts to scope the knowledge, attitudes and skills required to deliver education for Master's level mental health nurses based upon the principles of recovery and social inclusion. Emotional intelligence theory may help to identify desired outcomes especially in terms of attitudinal development to promote the philosophy of recovery and social inclusive approaches in advanced practice. Whilst recovery is becoming enshrined in policy, there is a need in higher education to ensure that mental health nurse leaders are able to discern the difference between the rhetoric and the reality. PMID- 26687143 TI - Formation and dissolution of microbubbles on highly-ordered plasmonic nanopillar arrays. AB - Bubble formation from plasmonic heating of nanostructures is of great interest in many applications. In this work, we study experimentally the intrinsic effects of the number of three-dimensional plasmonic nanostructures on the dynamics of microbubbles, largely decoupled from the effects of dissolved air. The formation and dissolution of microbubbles is observed on exciting groups of 1, 4, and 9 nanopillars. Our results show that the power threshold for the bubble formation depends on the number density of the nanopillars in highly-ordered arrays. In the degassed water, both the growth rate and the maximal radius of the plasmonic microbubbles increase with an increase of the illuminated pillar number, due to the heat balance between the heat loss across the bubble and the collective heating generated from the nanopillars. Interestingly, our results show that the bubble dissolution is affected by the spatial arrangement of the underlying nanopillars, due to the pinning effect on the bubble boundary. The bubbles on nanopillar arrays dissolve in a jumping mode with step-wise features on the dissolution curves, prior to a smooth dissolution phase for the bubble pinned by a single pillar. The insight from this work may facilitate the design of nanostructures for efficient energy conversion. PMID- 26687144 TI - Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation. AB - A unique, unsolved O-mannosyl glycan on alpha-dystroglycan is essential for its interaction with protein ligands in the extracellular matrix. Defective O mannosylation leads to a group of muscular dystrophies, called dystroglycanopathies. Mutations in isoprenoid synthase domain containing (ISPD) represent the second most common cause of these disorders, however, its molecular function remains uncharacterized. The human ISPD (hISPD) crystal structure showed a canonical N-terminal cytidyltransferase domain linked to a C-terminal domain that is absent in cytidyltransferase homologs. Functional studies demonstrated cytosolic localization of hISPD, and cytidyltransferase activity toward pentose phosphates, including ribulose 5-phosphate, ribose 5-phosphate, and ribitol 5 phosphate. Identity of the CDP sugars was confirmed by liquid chromatography quadrupole time-of-flight mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. Our combined results indicate that hISPD is a cytidyltransferase, suggesting the presence of a novel human nucleotide sugar essential for functional alpha-dystroglycan O-mannosylation in muscle and brain. Thereby, ISPD deficiency can be added to the growing list of tertiary dystroglycanopathies. PMID- 26687145 TI - Identification of markers linked to genes for sprouting tolerance (independent of grain color) in hard white winter wheat (HWWW). AB - KEY MESSAGE: Hard red wheats can donate genes to hard white wheats for tolerance to preharvest sprouting, the effects are quantitative in nature, and may be tracked with previously described DNA markers. ABSTRACT: Pre-harvest sprouting (PHS) of wheat (Triticum aestivum L.) can negatively impact end-use quality and seed viability at planting. Due to preferences for white over red wheat in international markets, white wheat with PHS tolerance has become increasingly desired for worldwide wheat production. In general, however, red wheat is more tolerant of sprouting than white wheat. The main objective of this study was the identification of PHS tolerance conditioned by genes donated from hard red winter wheat, using markers applicable to the Great Plains hard white wheat gene pool. Three red wheat by white wheat populations, Niobrara/NW99L7068, NE98466/NW99L7068 and Jagalene/NW99L7068 were developed, and white-seeded progenies were analyzed for PHS tolerance and used to identify markers for the trait. In the three populations, marker loci with significant allelic effects were most commonly located on chromosomes of group 2, 3, 4 and 5, though additional markers were detected across the wheat genome. Chromosome 3A was the only chromosome with significant markers in all three populations. Markers were inconsistent across the three populations, and markers linked to tolerance-inducing loci were identified in both tolerant and susceptible parents. Additive effects of marker loci were common. In the present investigation, a wide range of PHS tolerance was observed, even though all lines were fixed for the recently reported positive TaPHS1 allele. PHS tolerance is controlled by additive major gene effects with minor gene effects where variations of minor gene effects were still unclear. PMID- 26687146 TI - Refining the definition of the choroidal-scleral interface. PMID- 26687147 TI - A New Approach to Handle Missing Covariate Data in Twin Research : With an Application to Educational Achievement Data. AB - The often-used ACE model which decomposes phenotypic variance into additive genetic (A), common-environmental (C) and unique-environmental (E) parts can be extended to include covariates. Collection of these variables however often leads to a large amount of missing data, for example when self-reports (e.g. questionnaires) are not fully completed. The usual approach to handle missing covariate data in twin research results in reduced power to detect statistical effects, as only phenotypic and covariate data of individual twins with complete data can be used. Here we present a full information approach to handle missing covariate data that makes it possible to use all available data. A simulation study shows that, independent of missingness scenario, number of covariates or amount of missingness, the full information approach is more powerful than the usual approach. To illustrate the new method, we applied it to test scores on a Dutch national school achievement test (Eindtoets Basisonderwijs) in the final grade of primary school of 990 twin pairs. The effects of school-aggregated measures (e.g. school denomination, pedagogical philosophy, school size) and the effect of the sex of a twin on these test scores were tested. None of the covariates had a significant effect on individual differences in test scores. PMID- 26687149 TI - Effect of sublethal alpha-cypermethrin exposure on main macromolecules concentration, energy content, and malondialdehyde concentration in free-feeding Danio rerio larvae. AB - alpha-Cypermethrin (Cyp) is a synthetic insecticide used to control pests in agricultural crops and to protect human health against noxious insects; this toxic can reach aquatic systems through ground infiltration or by runoff and could affect the aquatic biota. The present study was aimed at evaluating the acute toxicity of Cyp on zebrafish (Danio rerio) exogenous feeding larvae of 10 and 20 days post-fertilization (dpf), and of sublethal concentrations on only 10 dpf larvae. Proteins, lipids, carbohydrates, glycogen concentration, and total energy contents, as well as malondialdehyde (MDA) quantification, through thiobarbituric acid reactive substances, as a lipid peroxidation biomarker, were assessed in free-feeding larvae exposed to sublethal Cyp concentrations. The LC50 for 10-dpf larvae was 1.94 ug L(-1), and these were more sensitive than 20-dpf larvae (3.56 ug L(-1)). The amount of protein, carbohydrates, and glycogen were not significantly affected (p > 0.05), but sublethal Cyp concentrations exposure caused decrement in lipids from 9.05 to 3.74 ug larva(-1), as well as a reduction in MDA and in the total energy content, which affected significantly the development of this fish. Although Cyp is considered an insecticide of reduced residual effect in the environment, the present study revealed that relatively low Cyp concentrations produced significant toxic effects on exogenous feeding fish larvae, a situation that could contribute to increase deaths during this already critical developmental stage in which high mortality is observed frequently. PMID- 26687151 TI - Primary Health Care: Expectations and Tasks for Public Health in Trinidad and Tobago. AB - The government of Trinidad and Tobago considers that the enjoyment of the highest attainable level of health is a basic right of every citizen and has a goal to achieve health for all by 2020. Thus it lays emphasis on caring and assures standards of excellence to promote, protect and improve the health status of the people of Trinidad and Tobago. To achieve these goals it is very important to increase curative services as well as preventive services in the country. In view of this situation there is a need to overcome the challenges the public health by involving community and individuals and self-reliance to achieve Health for all at 2020. Community participation is one of the domains of community capacity building in a small island country. It is one of the mechanisms to empower people to take part in community development. In this paper, the nature, the dimensions of community participation, and its role and scope in implementation of different components of primary health care have been described. The health services in public and remedial care have been discussed. The article highlights some important milestone achievements in the health sector in Trinidad. PMID- 26687150 TI - Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output. AB - Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17 years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.87 +/ 2.67 years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6 h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4 % (32.6 +/- 2.1 to 25.2 +/- 2.0 %, p < 0.001), rSO2 increased by 5.5 % (63.1 vs 68.6 %, p < 0.001), and serum lactate decreased by 0.9 mmol/l (3.3 vs 2.4 mmol/l, p < 0.001) with no change in HR (149.1 vs 145.6 bpm p = 0.07). Urine output increased 0.66 ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p = 0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions. PMID- 26687152 TI - [Tuberculosis of the breast: four cases report at the Armies Instruction's Hospital Omar Bongo Ondimba (HIAOBO) in Libreville (Gabon)]. AB - Mammary tuberculosis is a rare localization of extra pulmonary tuberculosis. Its frequency increases proportionally with the HIV pandemic. We report four cases of breast tuberculosis diagnosed in the general medicine department of HIAOBO including two with positive HIV serology. It is necessary to know this extra pulmonary form/feature as the differential diagnosis with breast tumors is sometimes difficult. PMID- 26687153 TI - Comment on "Treatment of Massive Labial and Gingival Hypertrophy in a Patient With Infantile Systemic Hyalinosis--A Case Report". PMID- 26687154 TI - Potential Indications for Tissue Engineering in Temporomandibular Joint Surgery. AB - PURPOSE: Musculoskeletal tissue engineering has advanced to the stage where it has the capability to engineer temporomandibular joint (TMJ) anatomic components. Unfortunately, there is a paucity of literature identifying specific indications for the use of TMJ tissue engineering solutions. The objective of this study was to establish an initial set of indications and contraindications for the use of engineered tissues for replacement of TMJ anatomic components. FINDINGS: There was consensus among the authors that the management of patients requiring TMJ reconstruction as the result of 1) irreparable condylar trauma, 2) developmental or acquired TMJ pathology in skeletally immature patients, 3) hyperplasia, and 4) documented metal hypersensitivities could be indications for bioengineered condyle and ramus TMJ components. There was consensus that Wilkes stage III internal derangement might be an indication for use of a bioengineered TMJ disc or possibly even a disc-like bioengineered "fossa liner." However, there was some controversy as to whether TMJ arthritic disease (e.g., osteoarthritis) and reconstruction after failed alloplastic devices should be indications. Further research is required to determine whether tissue-engineered TMJ components could be a viable option for such cases. Contraindications for the use of bioengineered TMJ components could include patients with TMJ disorders and multiple failed surgeries, parafunctional oral habits, persistent TMJ infection, TMJ rheumatoid arthritis, and ankylosis unless the underlying pathology can be resolved. CONCLUSIONS: Biomedical engineers must appreciate the specific indications that might warrant TMJ bioengineered structures, so that they avoid developing technologies in search of problems that might not exist for patients and clinicians. Instead, they should focus on identifying and understanding the problems that need resolution and then tailor technologies to address those specific situations. The aforementioned indications and contraindications are designed to serve as a guide to the next generation of tissue engineers in their strategic development of technologies to address specific clinical issues. PMID- 26687155 TI - Maxillofacial Gunshot Injuries: A Comparison of Civilian and Military Data. AB - PURPOSE: To compare military with civilian gunshot wounds (GSWs) in the maxillofacial region in order to establish differences in presentation, morbidity, and surgical management. MATERIALS AND METHODS: A cross-sectional study design was used. The University of Florida at Jacksonville oral and maxillofacial surgery operating room census and hospital trauma registry were both reviewed to identify maxillofacial GSW cases from 2005 through 2011. Military GSW data (2005 through 2011) were obtained from the US Department of Defense (DOD). The predictor variables were civilian versus military GSW events. The outcome variables of interest included the region of the face involved, race, gender, death during admission, hospital length of stay, and number of days in the intensive care unit (ICU). Descriptive statistics were computed. RESULTS: The sample was divided into military maxillofacial GSWs (n = 412) and civilian maxillofacial GSWs (n = 287 treated of 2,478 presented). A significant difference was measured between study groups regarding the region of the face involved (P = .0451), gender (P <= .0001), and race (P <= .0001). No significant relationship was measured regarding deaths during admission (P = .6510) for either study group. No standard deviation values for hospital length of stay or number of ICU days were provided by the DOD. The mean hospital length of stay for the military group was within the 95% confidence interval of the civilian group findings (6.0 7.6). The mean number of ICU days for the military group was not within the civilian group's 95% confidence interval (1.9-2.9). CONCLUSIONS: These data showed important differences in anatomic location, gender, and race distribution of maxillofacial GSWs between military and civilian populations. Limited analysis of hospital length of stay and number of ICU days might indicate no meaningful difference in hospital length of stay, although there was a statistical difference in the number of ICU days between the 2 populations. Future research comparing surgical strategies in these 2 environments could assist maxillofacial surgeons in providing optimal care to their patients. PMID- 26687156 TI - Catechol-O-Methyltransferase Gene Polymorphisms in Specific Obsessive-Compulsive Disorder Patients' Subgroups. AB - Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan((r)) or restriction mapping. We observed a statistically significant predominance of the Met low activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted. PMID- 26687157 TI - Biomechanics of dynamic cervical plates may influence clinical results. PMID- 26687159 TI - Integrins and adhesion molecules as targets to treat inflammatory bowel disease. AB - Inflammatory bowel diseases (IBD) present a typically relapsing-remitting behavior and are characterized by a disabling and progressive course. Anti-tumor necrosis factor (TNF)-alpha agents have drastically changed the therapeutic management of IBD. However, a significant proportion of patients does not have a primary response, some patients lose response overtime and/or experience side effects. Recently, anti-adhesion molecules were investigated and showed efficacy with a good safety profile. Vedolizumab was recently approved for both Crohn's disease (CD) and ulcerative colitis (UC) and several other molecules are under evaluation in this field. Anti-adhesion molecules could represent a potential therapeutic option for future therapy in IBD. In this review we report the efficacy and safety of major anti-adhesion drugs in active IBD patients. PMID- 26687158 TI - miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway. AB - AIMS/HYPOTHESIS: The mechanisms underlying the cellular metabolic memory induced by high glucose remain unclear. Here, we sought to determine the effects of microRNAs (miRNAs) on metabolic memory in diabetic retinopathy. METHODS: The miRNA microarray was used to examine human retinal endothelial cells (HRECs) following exposure to normal glucose (N) or high glucose (H) for 1 week or transient H for 2 days followed by N for another 5 days (H->N). Levels of sirtuin 1 (SIRT1) and acetylated-nuclear factor kappaB (Ac-NF-kappaB) were examined following transfection with miR-23b-3p inhibitor or with SIRT1 small interfering (si)RNA in the H->N group, and the apoptotic HRECs were determined by flow cytometry. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of miR-23b-3p inhibitor. Chromatin immunoprecipitation (ChIP) analysis was performed to detect binding of NF-kappaB p65 to the potential binding site of the miR-23b-27b-24-1 gene promoter in HRECs. RESULTS: High glucose increased miR-23b-3p expression, even after the return to normal glucose. Luciferase assays identified SIRT1 as a target mRNA of miR-23b-3p. Reduced miR 23b-3p expression inhibited Ac-NF-kappaB expression by rescuing SIRT1 expression and also relieved the effect of metabolic memory induced by high glucose in HRECs. The results were confirmed in the retina using a diabetic rat model of metabolic memory. High glucose facilitated the recruitment of NF-kappaB p65 and promoted transcription of the miR-23b-27b-24-1 gene, which can be suppressed by decreasing miR-23b-3p expression. CONCLUSIONS/INTERPRETATION: These studies identify a novel mechanism whereby miR-23b-3p regulates high-glucose-induced cellular metabolic memory in diabetic retinopathy through a SIRT1-dependent signalling pathway. PMID- 26687160 TI - Insertion/Insertion Genotype of Angiotensin I-Converting-Enzyme Gene Predicts Risk of Myocardial Infarction in North East India. AB - Myocardial infarction (MI) is common in India and the disease occurs at a relatively younger age. We wanted to look for association of Angiotensin I converting enzyme (ACE) gene with MI in North East India. We also wanted to examine possible environmental interaction of ACE gene with established cardiovascular risk factors in causation of MI. In the study carried out in Assam Medical College, 200 consecutive confirmed cases of MI were recruited. Equal numbers of age- and sex-matched control subjects from hospital workers and patients attending the hospital for diseases unrelated to cardiovascular disease were enrolled. Structured questionnaires were used to note demographic and clinical factors. Cardiovascular risk factors were determined from history, physical examination and biochemical investigations. ACE insertion/deletion (I/D) polymorphism was determined by PCR method. Interaction of ACE gene with other risk factors was noted. The study identified ACE II genotype (odds ratio = 3.02; 95% CI 1.40-6.51), smoking, hypertension, diabetes and serum triglyceride > 150 mg/dl as independent risk factors for MI. ACE II genotype showed greater risk in non-smokers, non-hypertensives, non-diabetics and in subjects with LDL-C < 130 mg/dl. Low HDL cholesterol enhanced the genetic risk. Subjects with ACE II genotype have an independent risk of developing MI, specially in low cardiovascular risk subjects. PMID- 26687162 TI - Analysis and quantitation of volatile organic compounds emitted from plastics used in museum construction by evolved gas analysis-gas chromatography-mass spectrometry. AB - Construction materials used in museums for the display, storage, and transportation of artwork must be assessed for their tendency to emit harmful pollution that could potentially damage cultural treasures. Traditionally, a subjective metals corrosion test known as the Oddy test has been widely utilized in museums for this purpose. To augment the Oddy test, an instrumental sampling approach based on evolved gas analysis (EGA) coupled to gas chromatography (GC) with mass spectral (MS) detection has been implemented for the first time to qualitatively identify off-gassed pollutants under specific conditions. This approach is compared to other instrumental methods reported in the literature. This novel application of the EGA sampling technique yields several benefits over traditional testing, including rapidity, high sensitivity, and broad detectability of volatile organic compounds (VOCs). Furthermore, unlike other reported instrumental approaches, the EGA method was used to determine quantitatively the amount of VOCs emitted by acetate resins and polyurethane foams under specific conditions using both an external calibration method as well as surrogate response factors. EGA was successfully employed to rapidly characterize emissions from 12 types of common plastics. This analysis is advocated as a rapid pre-screening method to rule out poorly performing materials prior to investing time and energy in Oddy testing. The approach is also useful for rapid, routine testing of construction materials previously vetted by traditional testing, but which may experience detrimental formulation changes over time. As an example, a case study on batch re-orders of rigid expanded poly(vinyl chloride) board stock is presented. PMID- 26687161 TI - Natural isoforms of the Photosystem II D1 subunit differ in photoassembly efficiency of the water-oxidizing complex. AB - Oxygenic photosynthesis efficiency at increasing solar flux is limited by light induced damage (photoinhibition) of Photosystem II (PSII), primarily targeting the D1 reaction center subunit. Some cyanobacteria contain two natural isoforms of D1 that function better under low light (D1:1) or high light (D1:2). Herein, rates and yields of photoassembly of the Mn4CaO5 water-oxidizing complex (WOC) from the free inorganic cofactors (Mn(2+), Ca(2+), water, electron acceptor) and apo-WOC-PSII are shown to differ significantly: D1:1 apo-WOC-PSII exhibits a 2.3 fold faster rate-limiting step of photoassembly and up to seven-fold faster rate to the first light-stable Mn(3+) intermediate, IM1*, but with a much higher rate of photoinhibition than D1:2. Conversely, D1:2 apo-WOC-PSII assembles slower but has up to seven-fold higher yield, achieved by a higher quantum yield of charge separation and slower photoinhibition rate. These results confirm and extend previous observations of the two holoenzymes: D1:2-PSII has a greater quantum yield of primary charge separation, faster [P680 (+) Q A (-) ] charge recombination and less photoinhibition that results in a slower rate and higher yield of photoassembly of its apo-WOC-PSII complex. In contrast, D1:1-PSII has a lower quantum yield of primary charge separation, a slower [P680 (+) Q A (-) ] charge recombination rate, and faster photoinhibition that together result in higher rate but lower yield of photoassembly at higher light intensities. Cyanobacterial PSII reaction centers that contain the high- and low-light D1 isoforms can tailor performance to optimize photosynthesis at varying light conditions, with similar consequences on their photoassembly kinetics and yield. These different efficiencies of photoassembly versus photoinhibition impose differential costs for biosynthesis as a function of light intensity. PMID- 26687163 TI - Development of gas chromatography-flame ionization detection system with a single column and liquid nitrogen-free for measuring atmospheric C2-C12 hydrocarbons. AB - A liquid nitrogen-free GC-FID system equipped with a single column has been developed for measuring atmospheric C2-C12 hydrocarbons. The system is consisted of a cooling unit, a sampling unit and a separation unit. The cooling unit is used to meet the temperature needs of the sampling unit and the separation unit. The sampling unit includes a dehydration tube and an enrichment tube. No breakthrough of the hydrocarbons was detected when the temperature of the enrichment tube was kept at -90 degrees C and sampling volume was 400 mL. The separation unit is a small round oven attached on the cooling column. A single capillary column (OV-1, 30 m * 0.32 mm I.D.) was used to separate the hydrocarbons. An optimal program temperature (-60 ~ 170 degrees C) of the oven was achieved to efficiently separate C2-C12 hydrocarbons. There were good linear correlations (R(2)=0.993-0.999) between the signals of the hydrocarbons and the enrichment amount of hydrocarbons, and the relative standard deviation (RSD) was less than 5%, and the method detection limits (MDLs) for the hydrocarbons were in the range of 0.02-0.10 ppbv for sampling volume of 400 mL. Field measurements were also conducted and more than 50 hydrocarbons from C2 to C12 were detected in Beijing city. PMID- 26687164 TI - Enantiomeric separations of alpha-aryl ketones with cyclofructan chiral stationary phases via high performance liquid chromatography and supercritical fluid chromatography. AB - Normal phase chiral HPLC and SFC methods are presented for the enantiomeric separation of 21 alpha-aryl ketones with a unique class of chiral stationary phases (CSPs) based on cyclofructans (CFs). Separations were achieved for all but 2 analytes, with 17 compounds attaining baseline separation having resolution values up to 4.0. Most separations obtained in HPLC could be transferred to SFC, but the HPLC resolutions were generally better due to greater enantiomeric selectivity values. A structure-separation relationship (SSR) was developed to identify important structural features for separation of this class of compounds using CF-based CSPs. Preliminary studies are also presented that demonstrate the utility of the CF CSPs to investigate the base-induced enantiomerization of alpha aryl ketones. It was demonstrated that even small amounts of base (0.01%v/v) in the mobile phase results in rapid, on-column, enantiomerization. Lastly, CSPs composed of superficially porous particles were used to achieve comparable separations of this class of chiral compounds, but at a fraction of the analysis time compared to CSPs composed of fully porous particles. PMID- 26687165 TI - Simultaneous determination of 200 pesticide residues in honey using gas chromatography-tandem mass spectrometry in conjunction with streamlined quantification approach. AB - A sensitive, accurate and reliable multi-class GC-MS/MS assay protocol for quantification and confirmation of 200 common agricultural pesticides in honey was developed and validated according to EU guidelines. A modified extraction procedure, based on QuEChERS method (quick, easy, cheap, effective, rugged and safe) was employed. Mass spectrophotometric conditions were individually optimized for each analyte to achieve maximum sensitivity and selectivity in MRM mode. The use of at least two reactions for each compound allowed simultaneous identification and quantification in a single run. The pesticides under investigation were separated in less than 31 min using the ultra-inert capillary column (DB-35MS). For all analytes, neat standard calibration curves in conjunction with correction for matrix effect were successfully employed. The detection limits of the assay ranged from 1.00 to 3.00 ng mL(-1) for the studied pesticides. The developed assay was linear over concentration range of 10.00 500.00 ng mL(-1), with correlation coefficient of more than 0.996. At the LOQ, 81% of the studied pesticides were efficiently recovered in the range of 70.00 120.00%, with CV% less than 15.00% while 99.3% compounds had mean percentage recovery of 60.00-140.00%, with CV% less than 21.00% (N=18, over three different days). The proposed assay was successfully applied for the analysis of the studied pesticide residues in one PT sample and 64 commercial honey samples collected over 1 year from different districts around Egypt. Results revealed that only one honey sample out of the 64 analyzed samples was contaminated with tau-Fluvalinate (10.00 MUg kg(-1)). This wide scope assay protocol is applicable for monitoring pesticide residues in honey by national regulatory authorities and accredited labs; that should help ensure safety of such widely used product. PMID- 26687166 TI - Field portable low temperature porous layer open tubular cryoadsorption headspace sampling and analysis part I: Instrumentation. AB - Building on the successful application in the laboratory of PLOT-cryoadsorption as a means of collecting vapor (or headspace) samples for chromatographic analysis, in this paper a field portable apparatus is introduced. This device fits inside of a briefcase (aluminum tool carrier), and can be easily transported by vehicle or by air. The portable apparatus functions entirely on compressed air, making it suitable for use in locations lacking electrical power, and for use in flammable and explosive environments. The apparatus consists of four aspects: a field capable PLOT-capillary platform, the supporting equipment platform, the service interface between the PLOT-capillary and the supporting equipment, and the necessary peripherals. Vapor sampling can be done with either a hand piece (containing the PLOT capillary) or with a custom fabricated standoff module. Both the hand piece and the standoff module can be heated and cooled to facilitate vapor collection and subsequent vapor sample removal. The service interface between the support platform and the sampling units makes use of a unique counter current approach that minimizes loss of cooling and heating due to heat transfer with the surroundings (recuperative thermostatting). Several types of PLOT-capillary elements and sampling probes are described in this report. Applications to a variety of samples relevant to forensic and environmental analysis are discussed in a companion paper. PMID- 26687167 TI - Ultra-fast high-efficiency enantioseparations by means of a teicoplanin-based chiral stationary phase made on sub-2 MUm totally porous silica particles of narrow size distribution. AB - A new ultra-high performance teicoplanin-based stationary phase was prepared starting from sub-2 MUm totally porous silica particles of narrow size distribution. Columns of different lengths were packed at high pressure and a deep and systematic evaluation of kinetic performance, in terms of van Deemter analysis, was performed under different elution conditions (HILIC, POM, RP and NP) by using both achiral and chiral probes. For the achiral probes, the efficiency of the columns at the minimum of the van Deemter curves were very high leading to some 278,000, 270,000, 262,000 and 232,000 plates/m in hydrophilic interaction liquid chromatography (HILIC), polar organic mode (POM), normal phase (NP) and reversed phase (RP) respectively. The lowest plate height, Hmin=3.59 MUm (h(/)=1.89), was obtained under HILIC conditions at a flow rate of 1.4 mL/min. Efficiency as high as 200,000-250,000 plates/m (at the optimum flow rate) was obtained in the separation of the enantiomers of chiral probes under HILIC/POM conditions. N-protected amino acids, alpha-aryloxy acids, herbicides, anti inflammatory agents were baseline separated on short (2-cm) and ultra-short (1 cm) columns, with analysis time in the order of 1 min. The enantiomers of N-BOC d,l-methionine were successfully baseline separated in only 11s in HILIC mode. Several examples of fast and efficient resolutions in sub/supercritical fluid chromatography were also obtained for a range of chiral carboxylic acids. PMID- 26687168 TI - Miniaturized ultra-high performance liquid chromatography coupled to electrochemical detection: Investigation of system performance for neurochemical analysis. AB - The interest in implementation of miniaturized ultra-high performance liquid chromatography (UHPLC) in neurochemical research is growing because of the need for faster, more selective and more sensitive neurotransmitter analyses. The instrument performance of a tailor designed microbore UHPLC system coupled to electrochemical detection (ECD) is investigated, focusing on the quantitative monoamine determination in in vivo microdialysis samples. The use of a microbore column (1.0mm I.D.) requires miniaturization of the entire instrument, though a balance between extra-column band broadening and injection volume must be considered. This is accomplished through the user defined Performance Optimizing Injection Sequence, whereby 5 MUL sample is injected on the column with a measured extra-column variance of 4.5-9.0 MUL(2) and only 7 MUL sample uptake. Different sub-2 MUm and superficially porous particle stationary phases are compared by means of the kinetic plot approach. Peak efficiencies of about 16000 35000 theoretical plates are obtained for the Acquity UPLC BEH C18 column within 13 min analysis time. Furthermore, the coupling to ECD is shown suitable for microbore UHPLC analysis thanks to the miniaturized flow cell design, sufficiently fast data acquisition and mathematical data filtering. Ultimately, injection of in vivo samples demonstrates the applicability of the system for microdialysis analysis. PMID- 26687169 TI - Qualitative and quantitative characterization of phenolic and diterpenoid constituents in Danshen (Salvia miltiorrhiza) by comprehensive two-dimensional liquid chromatography coupled with hybrid linear ion trap Orbitrap mass. AB - Danshen is one of the most frequently used traditional Chinese herbs owing to its remarkable and reliable therapeutic effects. Phenolic acids and diterpenoids have proved to be the bioactive substance groups. In order to fully profile its chemical compositions and explore new potential bioactive compounds, a comprehensive two-dimensional liquid chromatography system coupled to DAD detector and hybrid linear ion trap (LTQ) Orbitrap mass spectrometry (LC * LC-DAD ESI/HRMS/MS(n)) was set up in this study based on the column combination of Hypersil gold CN (150 mm * 1 mm, 3 MUm) and Accucore C18 (50 mm * 4.6 mm, 2.6 MUm). Using the optimal segment gradient program, phenolic acids and diterpenoids were separated into two independent groups and a total of 328 peaks were successfully detected on the contour plot of Danshen. By means of the accurate mass and reliable MS(n) data, 102 compounds were identified or tentatively identified and 7 of them were discovered from Danshen for the first time. Moreover, the LC * LC-DAD system was validated for the quantitative analysis of 14 bioactive analytes using the contour plot, exhibiting satisfactory linearity (r >= 0.9976) and high precision for both peak locating (<= 1.07%) and peak volume calculating (0.34%-4.11%). The established method could afford powerful separation capability, reliable identification data and accurate quantitative results, which is very suitable for analysis of complex herbal samples. PMID- 26687170 TI - A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis. AB - BACKGROUND: Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5 fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal adenocarcinoma. METHODS: A single patient with esophageal adenocarcinoma and on peritoneal dialysis for end-stage renal disease was treated with cisplatin 25 mg/m(2) on day 1 of weeks 1 and 5 and continuous infusional 5 fluorouracil 1000 mg/m(2)/day on days 1-4 of weeks 1 and 5 along with daily radiation therapy. Intense plasma and dialysate sampling was performed during the week 5 administration, followed by quantitation of platinum by atomic absorption spectrophotometry and 5-fluorouracil by LC-MS/MS. RESULTS: Following systemic administration, clearance of ultrafilterable (active) platinum over the first 6 h was 20.8 L/h, which is lower than previously reported clearance levels of ultrafilterable platinum. Total platinum AUC was 131 MUg h/mL, also higher than an AUC previously reported for total platinum in patients with normal renal function. Platinum-related material was detected in the peritoneal cavity, but this is likely inactive. 5-Fluorouracil penetrated the intraperitoneal cavity, but the contribution of peritoneal dialysis to drug clearance was negligible at 0.072 %. CONCLUSIONS: Administration of intravenous cisplatin and 5-fluorouracil chemotherapy to a patient treated with continuous ambulatory peritoneal dialysis is feasible, but clearance in dialysate is nominal, thus suggesting that dose reduction is indicated for cisplatin. Systemic drug administration results in limited intraperitoneal penetration of 5-fluorouracil and inactive platinum species. PMID- 26687171 TI - Long-term outcomes of tyrosine kinase inhibitor discontinuation in patients with metastatic renal cell carcinoma. AB - PURPOSE: The purpose of the current study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who interrupted vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy. METHODS: A retrospective analysis of medical records was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n = 505). Patients who achieved stable disease (SD) or a better response under TKI and later discontinued TKI treatment for any reason with the exception of disease progression were included in the analysis. RESULTS: We identified 32 patients (sunitinib = 20, sorafenib = 7, and pazopanib = 5). The responses to VEGFR-TKIs were complete response (CR, n = 4), partial response (PR, n = 11), SD (n = 15), and controlled but nonmeasurable response (n = 2). Median time to TKI discontinuation from the initiation of VEGFR-TKI therapy was 16.6 months (95 % CI 12.8-20.3), and the main cause of VEGFR-TKI discontinuation was toxicity (n = 19, 59.4 %). At the time of analysis, 16 patients had disease progression and one patient died. With a median follow-up duration of 51.7 months (range 11.5-87.6), median progression-free survival (PFS) after TKI discontinuation was 20.2 months (95 % CI 6.4-34.0). In multivariate analysis, the duration of TKI therapy (<1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (p = 0.045). Among 11 patients who were retreated with the same TKI, two patients (18.2 %) achieved PR and nine achieved SD (81.8 %). CONCLUSIONS: VEGFR-TKI could be interrupted at least temporarily when clinically warranted in patients with mRCC sufficiently controlled by TKIs. PMID- 26687172 TI - Effects of temperature on the final stages of sexual maturation in Atlantic salmon (Salmo salar L.). AB - Maturing male and female Atlantic salmon (Salmo salar L.) were held under three temperature regimes for 10 weeks between September and December: warm (constant 14-16 degrees C), ambient (decreasing from 11 to 5 degrees C), and cold (decreasing from 7 to 3 degrees C). Blood samples were analyzed for plasma steroid levels, and the fish were inspected for the presence of expressible milt (total volume and spermatocrit) and ovulation weekly. Samples of eggs were dry fertilized with milt stripped from three males held at the same temperatures and incubated until the eyed stage. In females, levels of plasma testosterone (T) and 17beta-oestradiol (E2) dropped as ovulation approached, concurrent with a rapid increase in levels of plasma 17alpha,20beta-dihydroxy-4-pregnen-3-one (17,20beta P). In males, levels of T and 11-ketotestosterone (11-KT) peaked 2-3 weeks after the first appearance of expressible milt, while levels of 17,20beta-P increased steadily and did not exhibit a definite peak. Exposure of females to cold water amplified and advanced the profiles of all three steroids compared with the ambient group, and increased the survival rates to the eyed egg stage. Cold water had no immediate effect on the male steroid profiles, but later, higher levels of 17,20beta-P were evident compared with both the ambient controls and the warm water group, while the effects on 11-KT and T were more variable. Exposure to warm water completely inhibited both milt production and ovulation. Moreover, warm water modulated the steroid profiles of the males with lower 11-KT levels compared with ambient controls and lower 17,20beta-P level compared with cold water-treated males. In females, warm water resulted in total inhibition of the peri-ovulatory peak in 17,20beta-P and prevented the normal decline of T and E2 levels associated with ovulation. The findings of the present study are highly relevant for broodstock management in aquaculture, as well in understanding the impact of climate change/temperature variability on wild salmon spawning. PMID- 26687173 TI - Communication and US-Somali Immigrant Human Papillomavirus (HPV) Vaccine Decision Making. AB - The current study uses a multiple goal theoretical perspective to explore how Somali immigrant families living in Ohio, USA, make decisions regarding whether to vaccinate their children against human papillomavirus (HPV)-a leading cause of cervical cancer. A focus was placed on the communication goals of parents in HPV vaccine discussions with their child and health care provider. Semi-structured interviews were audiotaped, transcribed, and analyzed using a grounded theory approach. Key themes are the implications of the vaccine for early sexual activity, confusion between HPV and HIV (human immunodeficiency virus), the perception that the HPV vaccine is unnecessary, uncertainty about the vaccine's efficacy and side effects, avoidance of parent-child communication about the vaccine, and a preference for framing the vaccine as a health promotion behavior. Framing the threat of HPV in the context of initiation of sexual activity, uncertainty regarding vaccine efficacy, and anticipated regret account for the inconsistency in HPV vaccine uptake among Somali parents. Clinicians should consider talking about HPV as a distal versus an immediate threat and HPV vaccine uptake as a health-promotion behavior rather than a sexually transmitted infection prevention behavior. PMID- 26687174 TI - Rethinking the Poverty-disease Nexus: the Case of HIV/AIDS in South Africa. AB - While it is well-established that poverty and disease are intimately connected, the nature of this connection and the role of poverty in disease causation remains contested in scientific and social studies of disease. Using the case of HIV/AIDS in South Africa and drawing on a theoretically grounded analysis, this paper reconceptualises disease and poverty as ontologically entangled. In the context of the South African HIV epidemic, this rethinking of the poverty-disease dynamic enables an account of how social forces such as poverty become embodied in the very substance of disease to produce ontologies of HIV/AIDS unique to South Africa. PMID- 26687175 TI - Uncovering the hidden facets of drought stress: secondary metabolites make the difference. PMID- 26687176 TI - Exploiting water versus tolerating drought: water-use strategies of trees in a secondary successional tropical dry forest. AB - In seasonal plant communities where water availability changes dramatically both between and within seasons, understanding the mechanisms that enable plants to exploit water pulses and to survive drought periods is crucial. By measuring rates of physiological processes, we examined the trade-off between water exploitation and drought tolerance among seedlings of trees of a tropical dry forest, and identified biophysical traits most closely associated with plant water-use strategies. We also explored whether early and late secondary successional species occupy different portions of trade-off axes. As predicted, species that maintained carbon capture, hydraulic function and leaf area at higher plant water deficits during drought had low photosynthetic rates, xylem hydraulic conductivity and growth rate under non-limiting water supply. Drought tolerance was associated with more dense leaf, stem and root tissues, whereas rapid resource acquisition was associated with greater stem water storage, larger vessel diameter and larger leaf area per mass invested. We offer evidence that the water exploitation versus drought tolerance trade-off drives species differentiation in the ability of tropical dry forest trees to deal with alternating water-drought pulses. However, we detected no evidence of strong functional differentiation between early and late successional species along the proposed trade-off axes, suggesting that the environmental gradient of water availability across secondary successional habitats in the dry tropics does not filter out physiological strategies of water use among species, at least at the seedling stage. PMID- 26687177 TI - Timing of Pulmonary Valve Replacement: How Much Can the Right Ventricle Dilate Before it Looses Its Remodeling Potential? AB - Congenital heart disease patients that develop secondary pulmonary regurgitation require a pulmonary valve replacement (PVR) in their follow-up. The indications for PVR in asymptomatic patients are debated. Most guidelines consider a RV end diastolic volume (RVEDV) over 150 ml/m(2) as an indication for PVR. We analyzed clinical, echocardiographic and MRI variables of patients that underwent a surgical PVR between September 2006 and February 2013. The included patients were asymptomatic, without pulmonary stenosis and with both pre- and post-surgery MRI. Thirty-five patients (74.3 % males) were included. Mean age at PVR was 25.8 years (SD = 7.18), and weight was 64.5 Kg (SD = 12.03). The main diagnosis was tetralogy of Fallot (n = 28), pulmonary atresia (n = 2), primary pulmonary regurgitation (n = 2) and pulmonary regurgitation after percutaneous treatment (n = 2). The maximal RVEDV pre-PVR was 267 ml/m(2), and right ventricular end systolic volume (RVESV) was 183 ml/m(2). RV size and function were established by MRI: Pre-PVR Post-PVR p RVEDV (ml/m(2)) 162 (SD = 39.1) 94 (SD = 23.6) <0.001 RVESV (ml/m(2)) 87 (SD = 28.9) 44 (SD = 15.7) <0.001 RVEF 44.8 % (SD = 8.17) 52 % (SD = 9.9) <0.001 Patients with a RVEDV under 170 ml/m(2) combined with a RVESV under 90 ml/m(2) had a favorable RV remodeling, defined as RVEDV under 110 ml/m(2) (sensitivity 87.5 %), RVESV under 55 ml/m(2) (sensitivity 100 %) and RVEF over 50 % (sensitivity 100 %). When deciding the optimal PVR timing in asymptomatic patients, both RVEDV and RVESV should be considered. Our results suggest that higher volumes than used in the clinical practice can achieve a good remodeling. Therefore, PVR could be performed later in the follow-up reducing the number of cardiac interventions. PMID- 26687178 TI - Early Initiation of Renal Replacement Therapy in Pediatric Heart Surgery Is Associated with Lower Mortality. AB - Acute kidney injury (AKI) is frequent in the postoperative period of pediatric heart surgery and leads to significant morbidity and mortality. Renal replacement therapies (RRTs) are often used to treat AKI; however, these therapies have also been associated with higher mortality rates. Earlier initiation of RRT might improve outcomes. This study aims to investigate the relationship between the RRT and morbidity and mortality after pediatric heart surgery. We performed a single center retrospective study of all children undergoing pediatric heart surgery between April 2010 and December 2012 at a tertiary children's hospital. A total of 480 patients were included. Of those, 109 (23 %) were neonates and 126 patients (26 %) developed AKI within the first 72 postoperative hours. Patients who developed AKI had longer PICU admissions [12 days (4-37.75) vs. 4 (2-11); p < 0.001] and hospital length of stay [27 (11-53) vs. 14 (8-24) p < 0.001] and higher mortality [22/126 (17.5 %) vs. 13/354 (3.7 %); p < 0.001]. RRT techniques were used in 32 (6.6 %) patients [18/109 (16 %) neonates and 14/371 (3.8 %) infants and children; p < 0.01], with 25 (78 %) receiving peritoneal dialysis (PD) and 7 (22 %) continuous RRT (CRRT). Patients who received PD within the first 24 postoperative hours had lower mortality compared with those in whom PD was initiated later [4/16 (25 %) vs. 4/9 (44.4 %)]. Mortality among patients who received CRRT was 28.6 % (2/7). No deaths were reported in patients treated with CRRT within the first 24 postoperative hours. Postoperative AKI is associated with higher mortality in children undergoing cardiac surgery. Early initiation of RRT, both PD in neonates and CRRT in pediatric patients, might improve morbidity and mortality associated with AKI. PMID- 26687179 TI - Two MYB transcription factors regulate flavonoid biosynthesis in pear fruit (Pyrus bretschneideri Rehd.). AB - Flavonoid compounds play important roles in the modern diet, and pear fruits are an excellent dietary source of these metabolites. However, information on the regulatory network of flavonoid biosynthesis in pear fruits is rare. In this work, 18 putative flavonoid-related MYB transcription factors (TFs) were screened by phylogenetic analysis and four of them were correlated with flavonoid biosynthesis patterns in pear fruits. Among these MYB-like genes, the specific functions of two novel MYB TFs, designated as PbMYB10b and PbMYB9, were further verified by both overexpression and RNAi transient assays. PbMYB10b, a PAP-type MYB TF with atypical motifs in its conserved region, regulated the anthocyanin and proanthocyanidin pathways by inducing the expression of PbDFR, but its function could be complemented by other MYB TFs. PbMYB9, a TT2-type MYB, not only acted as the specific activator of the proanthocyanidin pathway by activating the PbANR promoter, but also induced the synthesis of anthocyanins and flavonols by binding the PbUFGT1 promoter in pear fruits. The MYBCORE-like element has been identified in both the PbUFGT1 promoter and ANR promoters in most species, but it was not found in UFGT promoters isolated from other species. This finding was also supported by a yeast one-hybrid assay and thus enhanced the likelihood of the interaction between PbMYB9 and the PbUFGT1 promoter. PMID- 26687180 TI - A model for intracellular movement of Cauliflower mosaic virus: the concept of the mobile virion factory. AB - The genomes of many plant viruses have a coding capacity limited to <10 proteins, yet it is becoming increasingly clear that individual plant virus proteins may interact with several targets in the host for establishment of infection. As new functions are uncovered for individual viral proteins, virologists have realized that the apparent simplicity of the virus genome is an illusion that belies the true impact that plant viruses have on host physiology. In this review, we discuss our evolving understanding of the function of the P6 protein of Cauliflower mosaic virus (CaMV), a process that was initiated nearly 35 years ago when the CaMV P6 protein was first described as the 'major inclusion body protein' (IB) present in infected plants. P6 is now referred to in most articles as the transactivator (TAV)/viroplasmin protein, because the first viral function to be characterized for the Caulimovirus P6 protein beyond its role as an inclusion body protein (the viroplasmin) was its role in translational transactivation (the TAV function). This review will discuss the currently accepted functions for P6 and then present the evidence for an entirely new function for P6 in intracellular movement. PMID- 26687181 TI - Gestational Hypothyroxinemia Affects Glutamatergic Synaptic Protein Distribution and Neuronal Plasticity Through Neuron-Astrocyte Interplay. AB - Gestational hypothyroxinemia, characterized by low levels of maternal thyroxine (T4) during gestation, is closely associated with cognitive impairment in offspring. Studies in animal models have shown that this condition alters neuronal glutamatergic synapses in the hippocampus. Given that astrocytes critically contribute to the establishment and functioning of synapses, the aim of this study was to determine the effects of gestational hypothyroxinemia on the capacity of astrocytes to regulate glutamatergic synapses. In an in vitro co culture model of astrocytes and hippocampal neurons, gestational hypothyroxinemia profoundly affected the synaptic patterns of GluN1 and CD3zeta in an astrocyte dependent manner. These effects were associated with impaired plasticity that was dependent on both neuronal and astrocyte contributions. These results highlight the importance of neuron-astrocyte interplay in the deleterious effects of gestational hypothyroxinemia and the timely diagnosis and treatment of this condition during gestation to ensure proper central nervous system development in offspring. PMID- 26687183 TI - A Novel Functional Polymorphism in the NINJ2 Promoter Predicts Risk of Large Artery Atherosclerotic Stroke. AB - A recent genome-wide association study (GWAS) identified two common polymorphisms (rs12425791 and rs11833579) on chromosome 12p13 that confer risk to stroke, particularly for large artery atherosclerotic (LAA) stroke. However, these two polymorphisms are located ~11 kb upstream of the NINJ2 gene and their effects on NINJ2 expression have not been well characterized. Through linkage disequilibrium and fine-mapping analysis, we identified a novel functional polymorphism in the NINJ2 promoter (rs3809263 G > A) and examined its association with risk of LAA stroke in Chinese population. Rs3809263 was genotyped using the improved multiple ligase detection reaction in 414 patients with LAA stroke and 423 healthy controls. A significant decreased risk of LAA stroke was found for the rs3809263 GA (adjusted odd ratio [OR] = 0.63, 95 % confidence interval [CI] = 0.46-0.88) and AA (OR = 0.54, 95 % CI = 0.35-0.84) genotypes. Moreover, genotype-phenotype correlation analysis indicated that the AA genotype carriers had significantly increased NINJ2 mRNA expression levels in the Chinese population, suggesting that the rs3809263 G > A polymorphism is a functional SNP and a biomarker for risk of LAA stroke. Further validation of the functionality of the NINJ2 rs3809263 G > A polymorphism and its association with risk of LAA stroke in other ethnic populations is warranted. PMID- 26687182 TI - Differentiation of Human Endometrial Stem Cells into Schwann Cells in Fibrin Hydrogel as 3D Culture. AB - Human endometrial stem cells (hEnSCs) are a new source of adult multipotent stem cells with the ability of differentiation into many cell lineages. Many stem cell sources are desirable for differentiation into Schwann cells. Schwann-like cells derived from hEnSCs may be one of the ideal alternative cell sources for Schwann cell generation. In this study, for differentiation of hEnSCs into Schwann cells, hEnSCs were induced with RA/FSK/PDGF-AA/HRG as an induction medium for 14 days. The cells were cultured in a tissue culture plate (TCP) and fibrin gel matrix. The viability of cultured cells in the fibrin gel and TCP was analyzed with 3 [4,5-dimethyl-2-thia-zolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay for 7 days. The attachment of cells was analyzed with SEM and DAPI staining. The expression of S100 and P75 as Schwann cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR). The evaluation of the MTT assay and gene expression showed that the survival rate and differentiation of hEnSCs into Schwann cells in the fibrin gel were better than those in the TCP group. These results suggest that human EnSCs can be differentiated into Schwann cells in the fibrin gel better than in the TCP, and the fibrin gel might provide a suitable three-dimensional (3D) scaffold for clinical applications for cell therapy of the nervous system. PMID- 26687185 TI - Dihydromyricetin Improves Hypobaric Hypoxia-Induced Memory Impairment via Modulation of SIRT3 Signaling. AB - Inadequate oxygen availability-for instance at high altitudes-leads to hippocampal neurodegeneration and memory impairment. Although oxidative stress is one factor, the mechanism underlying the effects of hypobaric hypoxia (HH) are unclear, and effective strategies for preventing the resultant damage to the brain are limited. In the present study, we demonstrate that ingesting dihydromyricetin (DM) protects against memory impairment in adult rats subjected to HH for 7 days, equivalent to an altitude of 5000 m above sea level. Moreover, DM treatment stimulated mitochondrial biogenesis and improved mitochondrial morphology and function, suppressed the generation of reactive oxygen species, and reduced lipid peroxidation in the hippocampus. In HT-22 cells exposed to hypoxic conditions, the neuroprotective effects of DM were shown to be exerted via attenuation of oxidative stress through sirtuin 3-induced forkhead box O3 deacetylation. PMID- 26687184 TI - Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro. AB - Mesenchymal stem cells (MSCs) have recently been described to home to brain tumors and to integrate into the tumor-associated stroma. Understanding the communication between cancer cells and MSCs has become fundamental to determine whether MSC-tumor interactions should be exploited as a vehicle for therapeutic agents or considered a target for intervention. Therefore, we investigated whether conditioned medium from adipose-derived stem cells (ADSCs-CM) modulate glioma tumor cells by analyzing several cell biology processes in vitro. C6 rat glioma cells were treated with ADSCs-CM, and cell proliferation, cell cycle, cell viability, cell morphology, adhesion, migration, and expression of epithelial mesenchymal transition (EMT)-related surface markers were analyzed. ADSCs-CM did not alter cell viability, cell cycle, and growth rate of C6 glioma cells but increased their migratory capacity. Moreover, C6 cells treated with ADSC-CM showed reduced adhesion and underwent changes in cell morphology. Up-regulation of EMT-associated markers (vimentin, MMP2, and NRAS) was also observed following treatment with ADSC-CM. Our findings demonstrate that the paracrine factors released by ADSCs are able to modulate glioma cell biology. Therefore, ADSC-tumor cell interactions in a tumor microenvironment must be considered in the design of clinical application of stem cell therapy. Graphical Abstract Factors released by adipose-derived stem cells (ADSCs) may modulate the biology of C6 glioma cells. When C6 cells are exposed to a conditioned medium from adipose-derived stem cells (ADSCs-CM), some of these cells can undergo an EMT-like process and trans differentiate into cells with a more mesenchymal phenotype, characterized by enhanced expression of EMT-related surface markers, reduced cell adhesion capacity, increased migratory capacity, as well as changes in cell and nuclei morphology. PMID- 26687187 TI - Combined effects of n-TiO2 and 2,3,7,8-TCDD in Mytilus galloprovincialis digestive gland: A transcriptomic and immunohistochemical study. AB - Despite the growing concern over the potential biological impact of nanoparticles (NPs) in the aquatic environment, little is known about their interactions with other pollutants. In the marine mussel Mytilus galloprovincialis, exposure to nanosized titanium dioxide (n-TiO2), one of the most widespread type of NPs in use, in combination with and 2,3,7,8-tetrachlorodibenzo-p-dioxins (TCDD), chosen as model organic xenobiotic, was shown to induce significant changes in different biomarkers in hemocytes, gills and digestive gland, with distinct effects depending on cell/tissue and type of response measured. In this work, the interactive effects of n-TiO2 and TCDD at the tissue level were further investigated in mussel digestive gland using an integrated approach transcriptomics/immunohistochemistry. Mussels were exposed to n-TiO2 (100MUgL( 1)) and TCDD (0.25MUgL(-1)), alone and in combination, for 96h. Transcriptomic analysis identified 48-, 49- and 62 Differentially Expressed Genes (DEGs) in response to n-TiO2, TCDD and n-TiO2/TCDD, respectively. Gene Ontology (GO) term analysis revealed distinct biological processes affected in different experimental conditions. n-TiO2 mainly up-regulated cytoskeletal genes, while TCDD up-regulated endocrine and signal transduction related processes. Co exposure induced transcriptional changes common to individual treatments, and identified a newly generated process, response to chemical stimulus. Transcription of selected genes was verified by qPCR. Moreover, expression of tubulin, as an example of target protein of interest identified by gene transcription data, was evaluated in tissue sections by immunolabelling. Tissue TCDD accumulation was evaluated by immunofluorescence with an anti-dioxins antibody. The results demonstrate both distinct and interactive effects of n-TiO2 and TCDD in mussel digestive gland at the molecular and tissue level, identify the main molecular targets involved, and underline how exposure to the n TiO2/TCDD mixture does not result in increased TCDD accumulation and overall stressful conditions in the tissue. These represent the first data on transcriptional responses of marine invertebrates to exposure not only to n-TiO2 as a model of NP, but also to a legacy contaminant like TCDD. PMID- 26687186 TI - Attenuating Ischemic Disruption of K+ Homeostasis in the Cortex of Hypoxic Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment. AB - Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K+ homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K+ homeostasis to OGD. This response partially involves the activity of the delta-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K+ homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K+ homeostasis in the neonatal cortex. Since maintaining cellular K+ homeostasis and inhibiting excessive K+ fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K+ homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy. PMID- 26687188 TI - Evidence for Mitochondrial UPR Gene Activation in Familial and Sporadic Alzheimer's Disease. AB - Mitochondrial perturbations such as oxidative stress, increased fission/fusion dysfunction, and mitophagy are consistent features of Alzheimer's disease (AD), yet the mechanisms that initiate these perturbations are unclear. One potential source for mitochondrial defects could be an imbalance in mitochondrial proteostasis. In this regard, studies indicate that a specialized mitochondrial unfolded protein response (mtUPR) is activated upon the aberrant accumulation of damaged or unfolded proteins in the mitochondrial matrix, resulting in the up regulation of key genes involved in mitochondrial stabilization. To test whether mtUPR activation occurs in AD, we performed real-time quantitative PCR on postmortem frontal cortex samples from subjects classified as sporadic AD, familial AD linked to presenilin-1 mutations, or cognitively intact controls. Compared to controls, sporadic AD subjects exhibited a significant ~40-60% increase in expression levels of select genes activated by the mtUPR, including mitochondrial chaperones dnaja3, hspd1, and hspe1, mitochondrial proteases clpp and yme1l1, and txn2, a mitochondrial-specific oxidoreductase. Furthermore, levels of all six mtUPR genes were significantly up-regulated by ~70-90% in familial AD compared to controls, and these expression levels were significantly higher compared to sporadic AD. The increase in hspd1 (Hsp60) was validated by western blotting. These data support the concept that both sporadic and familial AD are characterized by mtUPR gene activation. Understanding the physiological consequences of this response may provide subcellular mechanistic clues to selective neuronal vulnerability or endogenous compensatory mechanisms during the progression of AD. PMID- 26687189 TI - Designing and Developing an Online Module: A 10-Step Approach. PMID- 26687190 TI - Electronic Nicotine Delivery System Use Among U.S. Adults, 2014. AB - INTRODUCTION: Electronic nicotine delivery system (ENDS) use has increased rapidly in the U.S. in recent years. The availability and use of ENDS raise new issues for public health practice and tobacco regulation, as it is unknown whether patterns of ENDS use enhance, deter, or have no impact on combustible tobacco product use. This study assessed past-month, lifetime, and frequency of ENDS use among current, former, and never adult cigarette smokers. METHODS: Data were analyzed from the 2014 Styles, a national consumer-based probability-based web panel survey of U.S. adults aged >=18 years (n=4,269) conducted during June and July. Lifetime ENDS users were defined as those who reported having used ENDS >=1 day in their lifetime. Past-month ENDS users were defined as those who reported using ENDS in the past 30 days. RESULTS: In 2014, overall lifetime and past-month ENDS use was 14.1% and 4.8%, respectively. By smoking status, 49.5% of current, 14.7% of former, and 4.1% of never cigarette smokers had used ENDS in their lifetime, whereas 20.6% of current, 4.0% of former, and 0.8% of never smokers used ENDS in the past month. Among current and former cigarette smokers who ever used ENDS, 44.1% and 44.7% reported using ENDS >10 days in their lifetime, respectively. CONCLUSIONS: Because the effect ENDS use has on combustible tobacco products use is unknown, and lifetime and past-month ENDS use is more common among current than former or never smokers, continued surveillance of ENDS use among adults is critical to programs and policies. PMID- 26687191 TI - Cyclodextrins in pharmaceutical formulations II: solubilization, binding constant, and complexation efficiency. AB - Cyclodextrins are cyclic oligosaccharides that have been recognized as pharmaceutical adjuvants for the past 20 years. The molecular structure of these glucose derivatives, which approximates a truncated cone, bucket, or torus, generates a hydrophilic exterior surface and a nonpolar interior cavity. Cyclodextrins can interact with appropriately sized drug molecules to yield an inclusion complex. These noncovalent inclusion complexes offer a variety of advantages over noncomplexed forms of a drug. Cyclodextrins are carbohydrates that are primarily used to enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Their other applications include preventing drug-drug interactions, converting liquid drugs into microcrystalline powders, minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell. Here, we focus on the solubilization of drugs by complexation, and discuss the determination and significance of binding constants for cyclodextrin complexes, and the determination of complexation efficiency and factors that influence it. We also make some general observations on cyclodextrin complexation and the use of cyclodextrins in solid, as well as parenteral, dosage forms. PMID- 26687193 TI - Editorial: Glial Cell Biology and Neurological Disease. PMID- 26687192 TI - Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer. AB - Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient-, tumor-, and treatment-related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence-free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23-39 years) with a median follow-up of 47 months (8-138 months). Breast conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty-two percent of patients had triple negative tumors (TN, ER-/PR-/HER2 nonamplified). Four-year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis. PMID- 26687194 TI - Clinical and biological significance of PIM1 kinase in osteosarcoma. AB - Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene serine/threonine-protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down regulation of anti-apoptotic protein Bcl-2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185-1194, 2016. PMID- 26687195 TI - Association of Sitagliptin with cardiovascular outcome in diabetic patients: a nationwide cohort study. AB - AIMS: Although dipeptidyl peptidase-4 (DPP-4) inhibitor improves glycemic control, the actual cardiovascular outcomes remain unclear. The objective of this cohort study was to thus evaluate the cardiovascular outcome in diabetic patients who received DPP-4 inhibitors (Sitagliptin). METHODS: A total of 104,756 new diabetic patients were identified from the Taiwan National Health Insurance Research Database during the period from March 1, 2003 to December 31, 2011. Patients who received Sitagliptin therapy were included as exposures, and up to four age- and sex-matched controls were selected by risk-set sampling. Outcomes such as major adverse cardiovascular diseases (CVD) and deaths were assessed. Logistic regression models were applied to estimate the hazard ratios and 95 % CIs between DPP-4 inhibitor use and cardiovascular outcome. RESULTS: Over a mean of 14 months, the rates of total CVD per 1000 person-months were significantly lower in Sitagliptin users (3.41 vs. 5.17, p < 0.001), whereas other different CVDs (hazard ratio [HR] 0.59; 95 % confidence interval [CI] 0.48-0.72 for coronary heart disease; HR 0.75; 95 % CI 0.59-0.96 for ischemic stroke; HR 0.86; 95 % CI 0.45-1.65 for peripheral artery occlusive disease) and all-cause mortality (HR 0.56; 95 % CI 0.41-0.74]) were also fewer after adjustment for covariates. CONCLUSIONS: The results showed a favorable outcome of Sitagliptin as a class on lowering CVD incidence in patients with type 2 diabetes. PMID- 26687196 TI - Assessment of arterial stiffness in type 1 diabetes using digital pulse contour analysis: Is it a reliable method? AB - AIMS: The aim of this study was to assess the arterial stiffness in patients with type 1 diabetes compared with a control group and determine the associated potential risk factors for its occurrence. METHODS: Fifty-seven subjects with type 1 diabetes and fifty-three healthy controls were submitted to clinical and laboratory evaluation. The peripheral waveform pressure was analyzed to assess arterial stiffness according to the reflection and stiffness index. RESULTS: Arterial stiffness did not differ between the controls and patients with type 1 diabetes. Pulse pressure showed no difference among both groups. In the group of patients with type 1 diabetes, the stiffness index was correlated with diabetes duration (r = 0.59, p < 0.001), body mass index (r = 0.27, p = 0.03), diastolic blood pressure (r = 0.33, p = 0.001), triglycerides (r = 0.35, p = 0.007), and age (r = 0.46, p < 0.001). The reflection index was correlated with the systolic blood pressure (r = 0.29, p = 0.02), diastolic blood pressure (r = 0.30, p = 0.02), and cardiac frequency (r = 0.48, p < 0.001). In the stepwise multivariate analysis, disease duration, diastolic blood pressure, and HDL cholesterol were the most important independent variables associated with arterial stiffness in patients with type 1 diabetes. CONCLUSIONS: We concluded that in the studied population, arterial stiffness showed no difference between patients with diabetes and controls; thus, the use of this method should not be indicated for routine clinical practice in type 1 diabetes. PMID- 26687197 TI - Triglycerides-to-HDL cholesterol ratio as screening tool for impaired glucose tolerance in obese children and adolescents. AB - AIMS: To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year). METHODS: Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose >=100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol >=2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol >=2.2. RESULTS: In the 148 obese children, TG/HDL-C >= 2.2 (OR 20.19; 95 % CI 2.50-163.28, p = 0.005) and the combination of TG/HDL-C >= 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18-102.76, p = 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C >= 2.2 (OR 1.991; 95 % CI 1.243-3.191, p = 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29-3.87, p = 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT. CONCLUSIONS: TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT. PMID- 26687198 TI - Intracellular Biosynthesis of Fluorescent CdSe Quantum Dots in Bacillus subtilis: A Strategy to Construct Signaling Bacterial Probes for Visually Detecting Interaction Between Bacillus subtilis and Staphylococcus aureus. AB - In this work, fluorescent Bacillus subtilis (B. subtilis) cells were developed as probes for imaging applications and to explore behaviorial interaction between B. subtilis and Staphylococcus aureus (S. aureus). A novel biological strategy of coupling intracellular biochemical reactions for controllable biosynthesis of CdSe quantum dots by living B. subtilis cells was demonstrated, through which highly luminant and photostable fluorescent B. subtilis cells were achieved with good uniformity. With the help of the obtained fluorescent B. subtilis cells probes, S. aureus cells responded to co-cultured B. subtilis and to aggregate. The degree of aggregation was calculated and nonlinearly fitted to a polynomial model. Systematic investigations of their interactions implied that B. subtilis cells inhibit the growth of neighboring S. aureus cells, and this inhibition was affected by both the growth stage and the amount of surrounding B. subtilis cells. Compared to traditional methods of studying bacterial interaction between two species, such as solid culture medium colony observation and imaging mass spectrometry detection, the procedures were more simple, vivid, and photostable due to the efficient fluorescence intralabeling with less influence on the cells' surface, which might provide a new paradigm for future visualization of microbial behavior. PMID- 26687199 TI - Development of a genome editing technique using the CRISPR/Cas9 system in the industrial filamentous fungus Aspergillus oryzae. AB - OBJECTIVES: To develop a genome editing method using the CRISPR/Cas9 system in Aspergillus oryzae, the industrial filamentous fungus used in Japanese traditional fermentation and for the production of enzymes and heterologous proteins. RESULTS: To develop the CRISPR/Cas9 system as a genome editing technique for A. oryzae, we constructed plasmids expressing the gene encoding Cas9 nuclease and single guide RNAs for the mutagenesis of target genes. We introduced these into an A. oryzae strain and obtained transformants containing mutations within each target gene that exhibited expected phenotypes. The mutational rates ranged from 10 to 20 %, and 1 bp deletions or insertions were the most commonly induced mutations. CONCLUSIONS: We developed a functional and versatile genome editing method using the CRISPR/Cas9 system in A. oryzae. This technique will contribute to the use of efficient targeted mutagenesis in many A. oryzae industrial strains. PMID- 26687200 TI - Identification and characterization of a novel antioxidant peptide from feather keratin hydrolysate. AB - OBJECTIVES: To improve the potential value of feather, which is a valuable protein resource, we have separated and identified antioxidant peptide(s) from feather hydrolysate. RESULTS: Feather hydrolysate was prepared by fermentation with Bacillus subtilis S1-4. Antioxidative peptides were separated by sequential acid precipitation, cation exchange, and reversed-phase fast performance liquid chromatography. Finally, a peptide with antioxidative activity was identified as Ser-Asn-Leu-Cys-Arg-Pro-Cys-Gly by MALDI time-of-flight (TOF)/TOF analysis, and determined to represent a portion of feather keratin near its N-terminal. A synthesized peptide with the same sequence was used to characterize its antioxidative properties, including scavenging free radicals, reducing power, and Fe(2+) chelation. In terms of the peptide's amino acid composition, the antioxidative activity might be mainly attributed to Cys and other amino acid residues. CONCLUSION: Feather keratin is a good source for the quantitative preparation of antioxidative peptides. PMID- 26687201 TI - Can we rely on simulated patients' satisfaction with their consultation for assessing medical students' communication skills? A cross-sectional study. AB - BACKGROUND: In medical education, teaching methods offering intensive practice without high utilization of faculty resources are needed. We investigated whether simulated patients' (SPs') satisfaction with a consultation could predict professional observers' assessment of young doctors' communication skills. METHODS: This was a comparative cross-sectional study of 62 videotaped consultations in a general practice setting with young doctors who were finishing their internship. The SPs played a female patient who had observed blood when using the toilet, which had prompted a fear of cancer. Immediately afterwards, the SP rated her level of satisfaction with the consultation, and the scores were dichotomized into satisfaction or dissatisfaction. Professional observers viewed the videotapes and assessed the doctors' communication skills using the Arizona Communication Interview Rating Scale (ACIR). Their ratings of communication skills were dichotomized into acceptable versus unacceptable levels of competence. RESULTS: The SPs' satisfaction showed a predictive power of 0.74 for the observers' assessment of the young doctors and whether they reached an acceptable level of communication skills. The SPs' dissatisfaction had a predictive power of 0.71 for the observers' assessment of an unacceptable communication level. The two assessment methods differed in 26% of the consultations. When SPs felt relief about their cancer concern after the consultation, they assessed the doctors' skills as satisfactory independent of the observers' assessment. CONCLUSIONS: Accordance between the dichotomized SPs' satisfaction score and communication skills assessed by observers (using the ACIR) was in the acceptable range. These findings suggest that SPs' satisfaction scores may provide a reliable source for assessing communication skills in educational programs for medical trainees (students and young doctors). Awareness of the patient's concerns seems to be of vital importance to patient satisfaction. PMID- 26687202 TI - Onset of Alcohol Use Disorders and Comorbid Psychiatric Disorders in a Military Cohort: Are there Critical Periods for Prevention of Alcohol Use Disorders? AB - Alcohol use disorders (AUD) are commonly comorbid with anxiety and mood disorders; however, a strategy for AUD prevention remains unclear in the presence of three competing etiological models that each recommends different high-risk groups. Therefore, the investigation of the three hypotheses in a characteristically unique cohort is critical to identifying pervasive characteristics of AUD that can inform a universal prevention strategy. The current study evaluated the temporality and onset of comorbid AUD and psychiatric disorders in a representative sample of 528 Ohio Army National Guard soldiers using structured clinical interviews from 2009 to 2012. We examined temporality both statistically and graphically to identify patterns that could inform prevention. General estimating equations with dichotomous predictor variables were used to estimate odds ratios between comorbid psychiatric disorders and AUDs. An annualized rate of 13.5 % persons per year was diagnosed with any AUD between 2010 and 2012. About an equal proportion of participants with comorbid psychiatric disorders and AUD initiated the psychiatric disorder prior to the AUD and half initiated the psychiatric disorder after the AUD. Regardless of onset, however, the majority (80 %) AUD initiated during a short interval between the ages of 16 and 23. Focused primary prevention during this narrow age range (16-23 years) may have the greatest potential to reduce population mental health burden of AUD, irrespective of the sequencing of comorbid psychiatric disorder. PMID- 26687203 TI - Do Gender and Exposure to Interparental Violence Moderate the Stability of Teen Dating Violence?: Latent Transition Analysis. AB - This study investigates the development, change, and stability of teen dating violence (TDV) victimization over time. Specifically, we identify distinct subgroups of adolescents based on past-year TDV victimization, whether adolescents change victimization statuses over time (e.g., from psychological victimization to physical victimization), and how exposure to interparental violence and gender influence the prevalence and stability of TDV statuses. Adolescents (N=1,042) from 7 public high schools in Texas participated in this longitudinal study. The Conflict in Adolescent Dating Relationships Inventory (CADRI) (Wolfe et al., Psychological Assessment, 13(2), 277-293, 2001) was used to identify victimization statuses. Latent Transition Analysis (LTA) with measurement invariance was used to examine transition probability of an individual's latent status at Wave3 or Wave4 given his or her latent status at Wave2 or Wave3. Gender and exposure to interparental violence was included as moderators in the LTA. Three statuses of TDV victimization were identified: (1) non-victims; (2) emotional/verbal victims; and (3) physical/psychological victims. LTA showed that the majority of adolescents stayed in the same status over time; however, female youth exposed to interparental violence were more likely to move from a less to more severe status over time compared to non exposed youth. This is among the first study to identify subgroups of TDV victimization and to examine the stability of group membership over time. Female youth exposed to interparental violence were more likely to remain in or move into a violent relationship compared to unexposed youth. PMID- 26687204 TI - The Outcomes of an Alcohol Prevention Program on Parents' Rule Setting and Self efficacy: a Bidirectional Model. AB - Most adolescents have their first encounter with alcohol in early or middle adolescence. Parents' rule setting about alcohol has been shown to be important to delay the onset and reduce the frequency of adolescents' alcohol drinking, but less is known about the potential role of parents' beliefs about their competence in and ability to influence their adolescents' drinking habits (i.e., parental self-efficacy [PSE], Bandura (Psychological Review, 84, 191-215, 1977). In this study, we examined the direction of influence between parents' rule setting and PSE as outcomes of the program "Prevention of Alcohol use in Students" (PAS), a prevention program aiming to reduce underage drinking by targeting parents and adolescents both separately and in a combined intervention. We tested two mediation processes in which the program would (a) have a direct effect on PSE, which in turn would increase parents' rule setting or (b) have a direct effect on parents' rule setting, which in turn would increase PSE. To examine these processes, we used a sample of 2562 parent-adolescent dyads (age 12 at baseline), followed annually over 3 years. The results showed that the combined intervention increased PSE via an increase in parents' rule setting. No significant effect of the intervention on rules about alcohol via PSE was found. This is the first study to test the mediation processes involving PSE and parental rule setting in an experimental context where parenting practices are being actively changed. The results suggest that giving parents concrete advice on how to deal with alcohol drinking in their adolescents and at the same time helping adolescents to develop healthy attitudes about alcohol drinking have a positive influence on parents' self-efficacy. PMID- 26687205 TI - Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options. AB - Pseudomonas aeruginosa is a leading cause of nosocomial infections and is responsible for ~10% of all hospital-acquired infections worldwide. It continues to pose a therapeutic challenge because of the high rate of morbidity and mortality associated with it and the possibility of development of drug resistance during therapy. Standard antibiotic regimes against P. aeruginosa are increasingly becoming ineffective due to the rise in drug resistance. With the scope for developing new antibiotics being limited, alternative treatment options are gaining more and more attention. A number of recent studies reported complementary and alternative treatment options to combat P. aeruginosa infections. Quorum sensing inhibitors, phages, probiotics, anti-microbial peptides, vaccine antigens and antimicrobial nanoparticles have the potential to act against drug resistant strains. Unfortunately, most studies considering alternative treatment options are still confined in the pre-clinical stages, although some of these findings have tremendous potential to be turned into valuable therapeutics. This review is intended to raise awareness of several novel approaches that can be considered further for combating drug resistant P. aeruginosa infections. PMID- 26687206 TI - Level of Awareness of Various Aspects of Lung Cancer Among College Teachers in India: Impact of Cancer Awareness Programmes in Prevention and Early Detection. AB - Lung cancer is one of the most common causes of cancer mortality among men in India and incidence is increasing, but actually, they are largely preventable diseases. In India, advanced stage at the time of presentation is responsible for high mortality and morbidity and early detection is the only way to reduce it. The purpose of this study is to know the level of awareness of various aspects of lung cancer among college teachers and impact of awareness programmes in its prevention and early detection. This assessment was part of Pink Chain Campaign-a campaign on cancer awareness. During the cancer awareness events in 2011-2013 at various women colleges in different parts in India, pre-test related to lung cancer was followed by awareness programme. Post-test using the same questionnaire was conducted at the end of interactive session, at 6 months and 1 year. A total of 872 out of 985 teachers participated in the study (overall response rate was 88.5 %). Mean age of the study population was 41.6 years (range 26-59 years). There was a significant increase in the level of knowledge regarding lung cancer at 6 months, and this was sustained at 1 year. Among teachers who were just asked yes or no question, 117 teachers (13.4 %) were smokers and 241 teachers (27.6 %) were alcoholics. Magazines and newspapers were sources for knowledge in 50-60 % of teachers, whereas approximately 30 % of teachers were educated by TV and Internet regarding various aspects of lung cancer. Post awareness at 6 months and 1 year, Pink Chain Campaign was the major source of knowledge related to lung cancer in more than 90 % of teachers by continuous and timely update on subject. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not going for check-up were ignorance (83.1 %), fear (30.1 %) and lethargic attitude (29.3 %) initially, but over time, lack of time, lethargic attitude and hesitation became important factors after knowing various aspects of lung cancer. Knowledge of lung cancer was very low among teachers. Overall awareness of risk factors, sign and symptoms, screening modalities of lung cancer has improved in a year along with practices related to smoking and alcohol, but there was not much improvement in people undergoing regular check-ups. To inculcate safe practices in the lifestyle of people, awareness programmes such as the Pink Chain Campaign should be conducted more widely and frequently. PMID- 26687207 TI - A Qualitative Exploration of Latinos' Perceptions About Skin Cancer: the Role of Gender and Linguistic Acculturation. AB - Latinos have the highest rate of skin cancers among U.S. minorities. Despite a rising incidence of melanoma-the deadliest form of skin cancer-and greater disease burden, Latinos tend to have poor awareness of skin cancer risk factors which may inhibit preventive action. We expanded on prior work by qualitatively examining potential moderators (i.e., gender, acculturation) of skin cancer perceptions among Latinos from El Barrio in Harlem, New York City. Four focus groups stratified by language (English/Spanish) and gender were conducted. Discussions were recorded, transcribed, and coded using thematic analysis. Thirty eight self-identified Latinos (32 % male) participated. Across groups, median age was 35 years; 50 % completed